id sid tid token lemma pos cord-014597-66vd2mdu 1 1 key key JJ cord-014597-66vd2mdu 2 1 : : : cord-014597-66vd2mdu 2 2 cord-014597 cord-014597 NNP cord-014597-66vd2mdu 2 3 - - HYPH cord-014597-66vd2mdu 2 4 66vd2mdu 66vd2mdu CD cord-014597-66vd2mdu 2 5 authors author NNS cord-014597-66vd2mdu 2 6 : : : cord-014597-66vd2mdu 3 1 nan nan NNP cord-014597-66vd2mdu 3 2 title title NN cord-014597-66vd2mdu 3 3 : : : cord-014597-66vd2mdu 3 4 Abstracts abstract NNS cord-014597-66vd2mdu 3 5 from from IN cord-014597-66vd2mdu 3 6 the the DT cord-014597-66vd2mdu 3 7 25th 25th JJ cord-014597-66vd2mdu 3 8 European European NNP cord-014597-66vd2mdu 3 9 Society Society NNP cord-014597-66vd2mdu 3 10 for for IN cord-014597-66vd2mdu 3 11 Animal Animal NNP cord-014597-66vd2mdu 3 12 Cell Cell NNP cord-014597-66vd2mdu 3 13 Technology Technology NNP cord-014597-66vd2mdu 3 14 Meeting meeting NN cord-014597-66vd2mdu 3 15 : : : cord-014597-66vd2mdu 3 16 Cell cell NN cord-014597-66vd2mdu 3 17 Technologies Technologies NNPS cord-014597-66vd2mdu 3 18 for for IN cord-014597-66vd2mdu 3 19 Innovative Innovative NNP cord-014597-66vd2mdu 3 20 Therapies Therapies NNPS cord-014597-66vd2mdu 3 21 : : : cord-014597-66vd2mdu 3 22 Lausanne Lausanne NNP cord-014597-66vd2mdu 3 23 , , , cord-014597-66vd2mdu 3 24 Switzerland Switzerland NNP cord-014597-66vd2mdu 3 25 . . . cord-014597-66vd2mdu 4 1 14 14 CD cord-014597-66vd2mdu 4 2 - - SYM cord-014597-66vd2mdu 4 3 17 17 CD cord-014597-66vd2mdu 4 4 May May NNP cord-014597-66vd2mdu 4 5 2017 2017 CD cord-014597-66vd2mdu 4 6 date date NN cord-014597-66vd2mdu 4 7 : : : cord-014597-66vd2mdu 4 8 2018 2018 CD cord-014597-66vd2mdu 4 9 - - HYPH cord-014597-66vd2mdu 4 10 03 03 CD cord-014597-66vd2mdu 4 11 - - SYM cord-014597-66vd2mdu 4 12 15 15 CD cord-014597-66vd2mdu 4 13 journal journal NN cord-014597-66vd2mdu 4 14 : : : cord-014597-66vd2mdu 5 1 BMC BMC NNP cord-014597-66vd2mdu 5 2 Proc proc NN cord-014597-66vd2mdu 5 3 DOI doi NN cord-014597-66vd2mdu 5 4 : : : cord-014597-66vd2mdu 6 1 10.1186 10.1186 CD cord-014597-66vd2mdu 6 2 / / SYM cord-014597-66vd2mdu 6 3 s12919 s12919 NNP cord-014597-66vd2mdu 6 4 - - HYPH cord-014597-66vd2mdu 6 5 018 018 CD cord-014597-66vd2mdu 6 6 - - HYPH cord-014597-66vd2mdu 6 7 0097-x 0097-x CD cord-014597-66vd2mdu 7 1 sha sha NNP cord-014597-66vd2mdu 7 2 : : : cord-014597-66vd2mdu 8 1 c26196c940aab1a9c43e70d5428672644d1e0972 c26196c940aab1a9c43e70d5428672644d1e0972 NNP cord-014597-66vd2mdu 8 2 doc_id doc_id CD cord-014597-66vd2mdu 8 3 : : : cord-014597-66vd2mdu 8 4 14597 14597 CD cord-014597-66vd2mdu 8 5 cord_uid cord_uid NNS cord-014597-66vd2mdu 8 6 : : : cord-014597-66vd2mdu 9 1 66vd2mdu 66vd2mdu CD cord-014597-66vd2mdu 9 2 nan nan NNP cord-014597-66vd2mdu 9 3 . . . cord-014597-66vd2mdu 10 1 a a DT cord-014597-66vd2mdu 10 2 Schematic schematic JJ cord-014597-66vd2mdu 10 3 representation representation NN cord-014597-66vd2mdu 10 4 of of IN cord-014597-66vd2mdu 10 5 CRISPR CRISPR NNP cord-014597-66vd2mdu 10 6 based base VBN cord-014597-66vd2mdu 10 7 synthetic synthetic JJ cord-014597-66vd2mdu 10 8 transcription transcription NN cord-014597-66vd2mdu 10 9 factor factor NN cord-014597-66vd2mdu 10 10 technology technology NN cord-014597-66vd2mdu 10 11 . . . cord-014597-66vd2mdu 11 1 b b LS cord-014597-66vd2mdu 11 2 mRNA mrna NN cord-014597-66vd2mdu 11 3 expression expression NN cord-014597-66vd2mdu 11 4 levels level NNS cord-014597-66vd2mdu 11 5 of of IN cord-014597-66vd2mdu 11 6 protein protein NN cord-014597-66vd2mdu 11 7 transport transport NN cord-014597-66vd2mdu 11 8 related relate VBN cord-014597-66vd2mdu 11 9 genes gene NNS cord-014597-66vd2mdu 11 10 ( ( -LRB- cord-014597-66vd2mdu 11 11 Napg Napg NNP cord-014597-66vd2mdu 11 12 , , , cord-014597-66vd2mdu 11 13 Rab5A rab5a NN cord-014597-66vd2mdu 11 14 and and CC cord-014597-66vd2mdu 11 15 Arpc1b Arpc1b NNP cord-014597-66vd2mdu 11 16 ) ) -RRB- cord-014597-66vd2mdu 11 17 . . . cord-014597-66vd2mdu 12 1 Background background VB cord-014597-66vd2mdu 12 2 An an DT cord-014597-66vd2mdu 12 3 increasing increase VBG cord-014597-66vd2mdu 12 4 number number NN cord-014597-66vd2mdu 12 5 of of IN cord-014597-66vd2mdu 12 6 biologics biologic NNS cord-014597-66vd2mdu 12 7 are be VBP cord-014597-66vd2mdu 12 8 entering enter VBG cord-014597-66vd2mdu 12 9 the the DT cord-014597-66vd2mdu 12 10 development development NN cord-014597-66vd2mdu 12 11 pipelines pipeline NNS cord-014597-66vd2mdu 12 12 of of IN cord-014597-66vd2mdu 12 13 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 12 14 companies company NNS cord-014597-66vd2mdu 12 15 [ [ -LRB- cord-014597-66vd2mdu 12 16 1 1 CD cord-014597-66vd2mdu 12 17 ] ] -RRB- cord-014597-66vd2mdu 12 18 . . . cord-014597-66vd2mdu 13 1 Today today NN cord-014597-66vd2mdu 13 2 , , , cord-014597-66vd2mdu 13 3 the the DT cord-014597-66vd2mdu 13 4 preferred preferred JJ cord-014597-66vd2mdu 13 5 production production NN cord-014597-66vd2mdu 13 6 host host NN cord-014597-66vd2mdu 13 7 for for IN cord-014597-66vd2mdu 13 8 therapeutic therapeutic JJ cord-014597-66vd2mdu 13 9 proteins protein NNS cord-014597-66vd2mdu 13 10 is be VBZ cord-014597-66vd2mdu 13 11 the the DT cord-014597-66vd2mdu 13 12 CHO CHO NNP cord-014597-66vd2mdu 13 13 cell cell NN cord-014597-66vd2mdu 13 14 line line NN cord-014597-66vd2mdu 13 15 . . . cord-014597-66vd2mdu 14 1 However however RB cord-014597-66vd2mdu 14 2 one one CD cord-014597-66vd2mdu 14 3 of of IN cord-014597-66vd2mdu 14 4 the the DT cord-014597-66vd2mdu 14 5 major major JJ cord-014597-66vd2mdu 14 6 hurdles hurdle NNS cord-014597-66vd2mdu 14 7 , , , cord-014597-66vd2mdu 14 8 especially especially RB cord-014597-66vd2mdu 14 9 for for IN cord-014597-66vd2mdu 14 10 the the DT cord-014597-66vd2mdu 14 11 production production NN cord-014597-66vd2mdu 14 12 of of IN cord-014597-66vd2mdu 14 13 non non JJ cord-014597-66vd2mdu 14 14 - - JJ cord-014597-66vd2mdu 14 15 antibody antibody JJ cord-014597-66vd2mdu 14 16 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 14 17 , , , cord-014597-66vd2mdu 14 18 is be VBZ cord-014597-66vd2mdu 14 19 host host NN cord-014597-66vd2mdu 14 20 cell cell NN cord-014597-66vd2mdu 14 21 - - HYPH cord-014597-66vd2mdu 14 22 related relate VBN cord-014597-66vd2mdu 14 23 proteolytic proteolytic JJ cord-014597-66vd2mdu 14 24 degradation degradation NN cord-014597-66vd2mdu 14 25 which which WDT cord-014597-66vd2mdu 14 26 can can MD cord-014597-66vd2mdu 14 27 drastically drastically RB cord-014597-66vd2mdu 14 28 impact impact VB cord-014597-66vd2mdu 14 29 developability developability NN cord-014597-66vd2mdu 14 30 and and CC cord-014597-66vd2mdu 14 31 timelines timeline NNS cord-014597-66vd2mdu 14 32 of of IN cord-014597-66vd2mdu 14 33 pipeline pipeline NN cord-014597-66vd2mdu 14 34 projects project NNS cord-014597-66vd2mdu 14 35 . . . cord-014597-66vd2mdu 15 1 Material material NN cord-014597-66vd2mdu 15 2 and and CC cord-014597-66vd2mdu 15 3 methods method NNS cord-014597-66vd2mdu 16 1 Spike spike NN cord-014597-66vd2mdu 16 2 - - HYPH cord-014597-66vd2mdu 16 3 in in NN cord-014597-66vd2mdu 16 4 : : : cord-014597-66vd2mdu 16 5 CHO CHO NNP cord-014597-66vd2mdu 16 6 cells cell NNS cord-014597-66vd2mdu 16 7 were be VBD cord-014597-66vd2mdu 16 8 cultivated cultivate VBN cord-014597-66vd2mdu 16 9 in in IN cord-014597-66vd2mdu 16 10 a a DT cord-014597-66vd2mdu 16 11 chemically chemically RB cord-014597-66vd2mdu 16 12 defined define VBN cord-014597-66vd2mdu 16 13 culture culture NN cord-014597-66vd2mdu 16 14 medium medium NN cord-014597-66vd2mdu 16 15 at at IN cord-014597-66vd2mdu 16 16 36.5 36.5 CD cord-014597-66vd2mdu 16 17 ° ° NN cord-014597-66vd2mdu 16 18 C/10 C/10 NNP cord-014597-66vd2mdu 16 19 % % NN cord-014597-66vd2mdu 16 20 CO CO NNP cord-014597-66vd2mdu 16 21 2 2 CD cord-014597-66vd2mdu 16 22 in in IN cord-014597-66vd2mdu 16 23 shake shake NN cord-014597-66vd2mdu 16 24 - - HYPH cord-014597-66vd2mdu 16 25 flasks flask NNS cord-014597-66vd2mdu 16 26 . . . cord-014597-66vd2mdu 17 1 When when WRB cord-014597-66vd2mdu 17 2 the the DT cord-014597-66vd2mdu 17 3 cells cell NNS cord-014597-66vd2mdu 17 4 reached reach VBD cord-014597-66vd2mdu 17 5 their -PRON- PRP$ cord-014597-66vd2mdu 17 6 maximum maximum JJ cord-014597-66vd2mdu 17 7 viable viable JJ cord-014597-66vd2mdu 17 8 density density NN cord-014597-66vd2mdu 17 9 , , , cord-014597-66vd2mdu 17 10 they -PRON- PRP cord-014597-66vd2mdu 17 11 were be VBD cord-014597-66vd2mdu 17 12 removed remove VBN cord-014597-66vd2mdu 17 13 by by IN cord-014597-66vd2mdu 17 14 centrifugation centrifugation NN cord-014597-66vd2mdu 17 15 and and CC cord-014597-66vd2mdu 17 16 the the DT cord-014597-66vd2mdu 17 17 conditioned condition VBN cord-014597-66vd2mdu 17 18 medium medium NN cord-014597-66vd2mdu 17 19 was be VBD cord-014597-66vd2mdu 17 20 collected collect VBN cord-014597-66vd2mdu 17 21 . . . cord-014597-66vd2mdu 18 1 A a DT cord-014597-66vd2mdu 18 2 model model NN cord-014597-66vd2mdu 18 3 mAb mab NN cord-014597-66vd2mdu 18 4 was be VBD cord-014597-66vd2mdu 18 5 spiked spike VBN cord-014597-66vd2mdu 18 6 into into IN cord-014597-66vd2mdu 18 7 the the DT cord-014597-66vd2mdu 18 8 conditioned condition VBN cord-014597-66vd2mdu 18 9 medium medium NN cord-014597-66vd2mdu 18 10 and and CC cord-014597-66vd2mdu 18 11 incubated incubate VBD cord-014597-66vd2mdu 18 12 at at IN cord-014597-66vd2mdu 18 13 37 37 CD cord-014597-66vd2mdu 18 14 ° ° NN cord-014597-66vd2mdu 18 15 C c NN cord-014597-66vd2mdu 18 16 ± ± NNP cord-014597-66vd2mdu 18 17 protease protease NN cord-014597-66vd2mdu 18 18 inhibitors inhibitor NNS cord-014597-66vd2mdu 18 19 . . . cord-014597-66vd2mdu 19 1 The the DT cord-014597-66vd2mdu 19 2 amount amount NN cord-014597-66vd2mdu 19 3 of of IN cord-014597-66vd2mdu 19 4 proteolytic proteolytic JJ cord-014597-66vd2mdu 19 5 degradation degradation NN cord-014597-66vd2mdu 19 6 was be VBD cord-014597-66vd2mdu 19 7 analysed analyse VBN cord-014597-66vd2mdu 19 8 by by IN cord-014597-66vd2mdu 19 9 western western JJ cord-014597-66vd2mdu 19 10 blot blot NN cord-014597-66vd2mdu 19 11 and and CC cord-014597-66vd2mdu 19 12 LC LC NNP cord-014597-66vd2mdu 19 13 - - HYPH cord-014597-66vd2mdu 19 14 MS MS NNP cord-014597-66vd2mdu 19 15 . . . cord-014597-66vd2mdu 20 1 Transcriptomics transcriptomic NNS cord-014597-66vd2mdu 20 2 : : : cord-014597-66vd2mdu 21 1 Total Total NNP cord-014597-66vd2mdu 21 2 RNA RNA NNP cord-014597-66vd2mdu 21 3 was be VBD cord-014597-66vd2mdu 21 4 extracted extract VBN cord-014597-66vd2mdu 21 5 after after IN cord-014597-66vd2mdu 21 6 3 3 CD cord-014597-66vd2mdu 21 7 days day NNS cord-014597-66vd2mdu 21 8 of of IN cord-014597-66vd2mdu 21 9 cell cell NN cord-014597-66vd2mdu 21 10 cultivation cultivation NN cord-014597-66vd2mdu 21 11 . . . cord-014597-66vd2mdu 22 1 RNA RNA NNP cord-014597-66vd2mdu 22 2 sequencing sequencing NN cord-014597-66vd2mdu 22 3 libraries library NNS cord-014597-66vd2mdu 22 4 were be VBD cord-014597-66vd2mdu 22 5 constructed construct VBN cord-014597-66vd2mdu 22 6 and and CC cord-014597-66vd2mdu 22 7 processed process VBN cord-014597-66vd2mdu 22 8 on on IN cord-014597-66vd2mdu 22 9 the the DT cord-014597-66vd2mdu 22 10 HiSeq HiSeq NNP cord-014597-66vd2mdu 22 11 2000 2000 CD cord-014597-66vd2mdu 22 12 platform platform NN cord-014597-66vd2mdu 22 13 from from IN cord-014597-66vd2mdu 22 14 Illumina Illumina NNP cord-014597-66vd2mdu 22 15 . . . cord-014597-66vd2mdu 23 1 Generation generation NN cord-014597-66vd2mdu 23 2 of of IN cord-014597-66vd2mdu 23 3 matriptase matriptase JJ cord-014597-66vd2mdu 23 4 knockout knockout NN cord-014597-66vd2mdu 23 5 : : : cord-014597-66vd2mdu 23 6 CHO CHO NNP cord-014597-66vd2mdu 23 7 - - HYPH cord-014597-66vd2mdu 23 8 K1 K1 NNP cord-014597-66vd2mdu 23 9 cells cell NNS cord-014597-66vd2mdu 23 10 were be VBD cord-014597-66vd2mdu 23 11 transfected transfecte VBN cord-014597-66vd2mdu 23 12 with with IN cord-014597-66vd2mdu 23 13 mRNA mrna NN cord-014597-66vd2mdu 23 14 encoding encode VBG cord-014597-66vd2mdu 23 15 " " '' cord-014597-66vd2mdu 23 16 transcription transcription NN cord-014597-66vd2mdu 23 17 activator activator NN cord-014597-66vd2mdu 23 18 - - HYPH cord-014597-66vd2mdu 23 19 like like JJ cord-014597-66vd2mdu 23 20 effector effector NN cord-014597-66vd2mdu 23 21 nucleases nuclease NNS cord-014597-66vd2mdu 23 22 " " '' cord-014597-66vd2mdu 23 23 or or CC cord-014597-66vd2mdu 23 24 " " `` cord-014597-66vd2mdu 23 25 zinc zinc NN cord-014597-66vd2mdu 23 26 finger finger NN cord-014597-66vd2mdu 23 27 nucleases nucleases NNP cord-014597-66vd2mdu 23 28 " " '' cord-014597-66vd2mdu 23 29 targeting target VBG cord-014597-66vd2mdu 23 30 matriptase matriptase NNP cord-014597-66vd2mdu 23 31 exon exon NNP cord-014597-66vd2mdu 23 32 2 2 CD cord-014597-66vd2mdu 23 33 . . . cord-014597-66vd2mdu 24 1 The the DT cord-014597-66vd2mdu 24 2 transfected transfecte VBN cord-014597-66vd2mdu 24 3 cells cell NNS cord-014597-66vd2mdu 24 4 were be VBD cord-014597-66vd2mdu 24 5 subsequently subsequently RB cord-014597-66vd2mdu 24 6 sorted sort VBN cord-014597-66vd2mdu 24 7 into into IN cord-014597-66vd2mdu 24 8 single single JJ cord-014597-66vd2mdu 24 9 cells cell NNS cord-014597-66vd2mdu 24 10 and and CC cord-014597-66vd2mdu 24 11 analysed analyse VBN cord-014597-66vd2mdu 24 12 for for IN cord-014597-66vd2mdu 24 13 frameshift frameshift NN cord-014597-66vd2mdu 24 14 mutations mutation NNS cord-014597-66vd2mdu 24 15 in in IN cord-014597-66vd2mdu 24 16 both both DT cord-014597-66vd2mdu 24 17 alleles allele NNS cord-014597-66vd2mdu 24 18 via via IN cord-014597-66vd2mdu 24 19 Sanger Sanger NNP cord-014597-66vd2mdu 24 20 sequencing sequencing NN cord-014597-66vd2mdu 24 21 . . . cord-014597-66vd2mdu 25 1 Cell cell NN cord-014597-66vd2mdu 25 2 cultivation cultivation NN cord-014597-66vd2mdu 25 3 : : : cord-014597-66vd2mdu 25 4 Fed Fed NNP cord-014597-66vd2mdu 25 5 batch batch NN cord-014597-66vd2mdu 25 6 cultivation cultivation NN cord-014597-66vd2mdu 25 7 was be VBD cord-014597-66vd2mdu 25 8 performed perform VBN cord-014597-66vd2mdu 25 9 in in IN cord-014597-66vd2mdu 25 10 15-mL 15-ml CD cord-014597-66vd2mdu 25 11 miniaturized miniaturized JJ cord-014597-66vd2mdu 25 12 bioreactors bioreactor NNS cord-014597-66vd2mdu 25 13 ( ( -LRB- cord-014597-66vd2mdu 25 14 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 25 15 ) ) -RRB- cord-014597-66vd2mdu 25 16 . . . cord-014597-66vd2mdu 26 1 Approximately approximately RB cord-014597-66vd2mdu 26 2 700 700 CD cord-014597-66vd2mdu 26 3 proteases protease NNS cord-014597-66vd2mdu 26 4 are be VBP cord-014597-66vd2mdu 26 5 known know VBN cord-014597-66vd2mdu 26 6 in in IN cord-014597-66vd2mdu 26 7 rodents rodent NNS cord-014597-66vd2mdu 26 8 . . . cord-014597-66vd2mdu 27 1 To to TO cord-014597-66vd2mdu 27 2 reduce reduce VB cord-014597-66vd2mdu 27 3 the the DT cord-014597-66vd2mdu 27 4 number number NN cord-014597-66vd2mdu 27 5 of of IN cord-014597-66vd2mdu 27 6 candidate candidate NN cord-014597-66vd2mdu 27 7 proteases protease NNS cord-014597-66vd2mdu 27 8 we -PRON- PRP cord-014597-66vd2mdu 27 9 showed show VBD cord-014597-66vd2mdu 27 10 first first RB cord-014597-66vd2mdu 27 11 that that IN cord-014597-66vd2mdu 27 12 a a DT cord-014597-66vd2mdu 27 13 model model NN cord-014597-66vd2mdu 27 14 mAb mAb NNS cord-014597-66vd2mdu 27 15 ( ( -LRB- cord-014597-66vd2mdu 27 16 prone prone JJ cord-014597-66vd2mdu 27 17 to to IN cord-014597-66vd2mdu 27 18 proteolytic proteolytic JJ cord-014597-66vd2mdu 27 19 degradation degradation NN cord-014597-66vd2mdu 27 20 ) ) -RRB- cord-014597-66vd2mdu 27 21 incubated incubate VBN cord-014597-66vd2mdu 27 22 in in IN cord-014597-66vd2mdu 27 23 conditioned condition VBN cord-014597-66vd2mdu 27 24 medium medium NN cord-014597-66vd2mdu 27 25 of of IN cord-014597-66vd2mdu 27 26 CHO CHO NNP cord-014597-66vd2mdu 27 27 - - HYPH cord-014597-66vd2mdu 27 28 K1 K1 NNP cord-014597-66vd2mdu 27 29 cells cell NNS cord-014597-66vd2mdu 27 30 resulted result VBD cord-014597-66vd2mdu 27 31 in in IN cord-014597-66vd2mdu 27 32 clipping clip VBG cord-014597-66vd2mdu 27 33 of of IN cord-014597-66vd2mdu 27 34 the the DT cord-014597-66vd2mdu 27 35 mAb mAb NNS cord-014597-66vd2mdu 27 36 , , , cord-014597-66vd2mdu 27 37 demonstrating demonstrate VBG cord-014597-66vd2mdu 27 38 the the DT cord-014597-66vd2mdu 27 39 involvement involvement NN cord-014597-66vd2mdu 27 40 of of IN cord-014597-66vd2mdu 27 41 secreted secrete VBN cord-014597-66vd2mdu 27 42 / / SYM cord-014597-66vd2mdu 27 43 shedded shedde VBN cord-014597-66vd2mdu 27 44 proteases protease NNS cord-014597-66vd2mdu 27 45 ( ( -LRB- cord-014597-66vd2mdu 27 46 Fig Fig NNP cord-014597-66vd2mdu 27 47 . . . cord-014597-66vd2mdu 27 48 1a 1a CD cord-014597-66vd2mdu 27 49 ) ) -RRB- cord-014597-66vd2mdu 27 50 . . . cord-014597-66vd2mdu 28 1 Broad broad JJ cord-014597-66vd2mdu 28 2 spectrum spectrum NN cord-014597-66vd2mdu 28 3 inhibitors inhibitor NNS cord-014597-66vd2mdu 28 4 of of IN cord-014597-66vd2mdu 28 5 the the DT cord-014597-66vd2mdu 28 6 different different JJ cord-014597-66vd2mdu 28 7 protease protease NN cord-014597-66vd2mdu 28 8 classes class NNS cord-014597-66vd2mdu 28 9 revealed reveal VBD cord-014597-66vd2mdu 28 10 that that IN cord-014597-66vd2mdu 28 11 only only JJ cord-014597-66vd2mdu 28 12 serine serine NN cord-014597-66vd2mdu 28 13 protease protease NN cord-014597-66vd2mdu 28 14 inhibitors inhibitor NNS cord-014597-66vd2mdu 28 15 prevented prevent VBD cord-014597-66vd2mdu 28 16 clipping clip VBG cord-014597-66vd2mdu 28 17 . . . cord-014597-66vd2mdu 29 1 Serine serine NN cord-014597-66vd2mdu 29 2 protease protease NN cord-014597-66vd2mdu 29 3 inhibitors inhibitor NNS cord-014597-66vd2mdu 29 4 of of IN cord-014597-66vd2mdu 29 5 higher high JJR cord-014597-66vd2mdu 29 6 specificity specificity NN cord-014597-66vd2mdu 29 7 highlighted highlight VBD cord-014597-66vd2mdu 29 8 the the DT cord-014597-66vd2mdu 29 9 group group NN cord-014597-66vd2mdu 29 10 of of IN cord-014597-66vd2mdu 29 11 " " `` cord-014597-66vd2mdu 29 12 S1A s1a NN cord-014597-66vd2mdu 29 13 trypsin trypsin NN cord-014597-66vd2mdu 29 14 - - HYPH cord-014597-66vd2mdu 29 15 like like JJ cord-014597-66vd2mdu 29 16 proteases protease NNS cord-014597-66vd2mdu 29 17 " " '' cord-014597-66vd2mdu 29 18 ( ( -LRB- cord-014597-66vd2mdu 29 19 Fig fig NN cord-014597-66vd2mdu 29 20 . . . cord-014597-66vd2mdu 29 21 1a 1a CD cord-014597-66vd2mdu 29 22 ) ) -RRB- cord-014597-66vd2mdu 29 23 . . . cord-014597-66vd2mdu 30 1 Comparison comparison NN cord-014597-66vd2mdu 30 2 of of IN cord-014597-66vd2mdu 30 3 the the DT cord-014597-66vd2mdu 30 4 proteolytic proteolytic JJ cord-014597-66vd2mdu 30 5 degradation degradation NN cord-014597-66vd2mdu 30 6 profile profile NN cord-014597-66vd2mdu 30 7 of of IN cord-014597-66vd2mdu 30 8 several several JJ cord-014597-66vd2mdu 30 9 therapeutic therapeutic JJ cord-014597-66vd2mdu 30 10 proteins protein NNS cord-014597-66vd2mdu 30 11 between between IN cord-014597-66vd2mdu 30 12 CHO CHO NNP cord-014597-66vd2mdu 30 13 - - HYPH cord-014597-66vd2mdu 30 14 K1 K1 NNP cord-014597-66vd2mdu 30 15 with with IN cord-014597-66vd2mdu 30 16 another another DT cord-014597-66vd2mdu 30 17 CHO CHO NNP cord-014597-66vd2mdu 30 18 cell cell NN cord-014597-66vd2mdu 30 19 line line NN cord-014597-66vd2mdu 30 20 ( ( -LRB- cord-014597-66vd2mdu 30 21 CHO CHO NNP cord-014597-66vd2mdu 30 22 - - HYPH cord-014597-66vd2mdu 30 23 A A NNP cord-014597-66vd2mdu 30 24 ) ) -RRB- cord-014597-66vd2mdu 30 25 revealed reveal VBN cord-014597-66vd2mdu 30 26 less less JJR cord-014597-66vd2mdu 30 27 degradation degradation NN cord-014597-66vd2mdu 30 28 in in IN cord-014597-66vd2mdu 31 1 CHO CHO NNP cord-014597-66vd2mdu 31 2 - - HYPH cord-014597-66vd2mdu 31 3 A. A. NNP cord-014597-66vd2mdu 31 4 Therefore Therefore NNP cord-014597-66vd2mdu 31 5 expression expression NN cord-014597-66vd2mdu 31 6 of of IN cord-014597-66vd2mdu 31 7 the the DT cord-014597-66vd2mdu 31 8 involved involved JJ cord-014597-66vd2mdu 31 9 protease(s protease(s NNP cord-014597-66vd2mdu 31 10 ) ) -RRB- cord-014597-66vd2mdu 31 11 is be VBZ cord-014597-66vd2mdu 31 12 likely likely RB cord-014597-66vd2mdu 31 13 lower low JJR cord-014597-66vd2mdu 31 14 in in IN cord-014597-66vd2mdu 31 15 CHO CHO NNP cord-014597-66vd2mdu 31 16 - - HYPH cord-014597-66vd2mdu 31 17 A. A. NNP cord-014597-66vd2mdu 31 18 Gene Gene NNP cord-014597-66vd2mdu 31 19 expression expression NN cord-014597-66vd2mdu 31 20 profile profile NN cord-014597-66vd2mdu 31 21 analysis analysis NN cord-014597-66vd2mdu 31 22 of of IN cord-014597-66vd2mdu 31 23 both both DT cord-014597-66vd2mdu 31 24 cell cell NN cord-014597-66vd2mdu 31 25 lines line NNS cord-014597-66vd2mdu 32 1 showed show VBD cord-014597-66vd2mdu 32 2 five five CD cord-014597-66vd2mdu 32 3 secreted secrete VBN cord-014597-66vd2mdu 32 4 / / SYM cord-014597-66vd2mdu 32 5 shedded shedde VBD cord-014597-66vd2mdu 32 6 " " `` cord-014597-66vd2mdu 32 7 S1A s1a NN cord-014597-66vd2mdu 32 8 trypsin trypsin NN cord-014597-66vd2mdu 32 9 - - HYPH cord-014597-66vd2mdu 32 10 like like JJ cord-014597-66vd2mdu 32 11 serine serine NN cord-014597-66vd2mdu 32 12 proteases protease NNS cord-014597-66vd2mdu 32 13 " " '' cord-014597-66vd2mdu 32 14 more more JJR cord-014597-66vd2mdu 32 15 than than IN cord-014597-66vd2mdu 32 16 1.5 1.5 CD cord-014597-66vd2mdu 32 17 fold fold VB cord-014597-66vd2mdu 32 18 lower lower RBR cord-014597-66vd2mdu 32 19 expressed express VBN cord-014597-66vd2mdu 32 20 in in IN cord-014597-66vd2mdu 32 21 CHO CHO NNP cord-014597-66vd2mdu 32 22 - - HYPH cord-014597-66vd2mdu 32 23 CHO CHO NNP cord-014597-66vd2mdu 32 24 - - HYPH cord-014597-66vd2mdu 32 25 A A NNP cord-014597-66vd2mdu 32 26 versus versus IN cord-014597-66vd2mdu 32 27 CHO CHO NNP cord-014597-66vd2mdu 32 28 - - HYPH cord-014597-66vd2mdu 32 29 K1 K1 NNP cord-014597-66vd2mdu 32 30 ( ( -LRB- cord-014597-66vd2mdu 32 31 Fig Fig NNP cord-014597-66vd2mdu 32 32 . . . cord-014597-66vd2mdu 32 33 1b 1b CD cord-014597-66vd2mdu 32 34 ) ) -RRB- cord-014597-66vd2mdu 32 35 . . . cord-014597-66vd2mdu 33 1 Surprisingly surprisingly RB cord-014597-66vd2mdu 33 2 , , , cord-014597-66vd2mdu 33 3 siRNA siRNA NNP cord-014597-66vd2mdu 33 4 knockdown knockdown NN cord-014597-66vd2mdu 33 5 experiments experiment NNS cord-014597-66vd2mdu 33 6 of of IN cord-014597-66vd2mdu 33 7 these these DT cord-014597-66vd2mdu 33 8 five five CD cord-014597-66vd2mdu 33 9 candidates candidate NNS cord-014597-66vd2mdu 33 10 identified identify VBD cord-014597-66vd2mdu 33 11 " " `` cord-014597-66vd2mdu 33 12 Matriptase Matriptase NNP cord-014597-66vd2mdu 33 13 " " '' cord-014597-66vd2mdu 33 14 as as IN cord-014597-66vd2mdu 33 15 the the DT cord-014597-66vd2mdu 33 16 major major JJ cord-014597-66vd2mdu 33 17 protease protease NN cord-014597-66vd2mdu 33 18 involved involve VBN cord-014597-66vd2mdu 33 19 in in IN cord-014597-66vd2mdu 33 20 degradation degradation NN cord-014597-66vd2mdu 33 21 of of IN cord-014597-66vd2mdu 33 22 recombinant recombinant JJ cord-014597-66vd2mdu 33 23 proteins protein NNS cord-014597-66vd2mdu 33 24 expressed express VBN cord-014597-66vd2mdu 33 25 in in IN cord-014597-66vd2mdu 33 26 CHO CHO NNP cord-014597-66vd2mdu 33 27 - - HYPH cord-014597-66vd2mdu 33 28 K1 K1 NNP cord-014597-66vd2mdu 33 29 cells cell NNS cord-014597-66vd2mdu 33 30 ( ( -LRB- cord-014597-66vd2mdu 33 31 Fig fig NN cord-014597-66vd2mdu 33 32 . . . cord-014597-66vd2mdu 34 1 1c 1c NNP cord-014597-66vd2mdu 34 2 upper upper NNP cord-014597-66vd2mdu 34 3 panel panel NN cord-014597-66vd2mdu 34 4 ) ) -RRB- cord-014597-66vd2mdu 34 5 . . . cord-014597-66vd2mdu 35 1 Next next RB cord-014597-66vd2mdu 35 2 , , , cord-014597-66vd2mdu 35 3 we -PRON- PRP cord-014597-66vd2mdu 35 4 generated generate VBD cord-014597-66vd2mdu 35 5 a a DT cord-014597-66vd2mdu 35 6 CHO CHO NNP cord-014597-66vd2mdu 35 7 - - HYPH cord-014597-66vd2mdu 35 8 K1 K1 NNP cord-014597-66vd2mdu 35 9 matriptase matriptase NN cord-014597-66vd2mdu 35 10 knockout knockout NN cord-014597-66vd2mdu 35 11 ( ( -LRB- cord-014597-66vd2mdu 35 12 KO KO NNP cord-014597-66vd2mdu 35 13 ) ) -RRB- cord-014597-66vd2mdu 35 14 cell cell NN cord-014597-66vd2mdu 35 15 line line NN cord-014597-66vd2mdu 35 16 . . . cord-014597-66vd2mdu 36 1 No no DT cord-014597-66vd2mdu 36 2 proteolytic proteolytic JJ cord-014597-66vd2mdu 36 3 degradation degradation NN cord-014597-66vd2mdu 36 4 product product NN cord-014597-66vd2mdu 36 5 was be VBD cord-014597-66vd2mdu 36 6 detected detect VBN cord-014597-66vd2mdu 36 7 when when WRB cord-014597-66vd2mdu 36 8 the the DT cord-014597-66vd2mdu 36 9 model model NN cord-014597-66vd2mdu 36 10 mAb mAb NNP cord-014597-66vd2mdu 36 11 was be VBD cord-014597-66vd2mdu 36 12 spiked spike VBN cord-014597-66vd2mdu 36 13 into into IN cord-014597-66vd2mdu 36 14 conditioned condition VBN cord-014597-66vd2mdu 36 15 medium medium NN cord-014597-66vd2mdu 36 16 of of IN cord-014597-66vd2mdu 36 17 the the DT cord-014597-66vd2mdu 36 18 KO KO NNP cord-014597-66vd2mdu 36 19 cell cell NN cord-014597-66vd2mdu 36 20 line line NN cord-014597-66vd2mdu 36 21 ( ( -LRB- cord-014597-66vd2mdu 36 22 Fig Fig NNP cord-014597-66vd2mdu 36 23 . . . cord-014597-66vd2mdu 36 24 1c 1c NNP cord-014597-66vd2mdu 36 25 lower low JJR cord-014597-66vd2mdu 36 26 panel panel NN cord-014597-66vd2mdu 36 27 ) ) -RRB- cord-014597-66vd2mdu 36 28 . . . cord-014597-66vd2mdu 37 1 Also also RB cord-014597-66vd2mdu 37 2 , , , cord-014597-66vd2mdu 37 3 stable stable JJ cord-014597-66vd2mdu 37 4 expression expression NN cord-014597-66vd2mdu 37 5 of of IN cord-014597-66vd2mdu 37 6 the the DT cord-014597-66vd2mdu 37 7 model model NN cord-014597-66vd2mdu 37 8 mAb mab NN cord-014597-66vd2mdu 37 9 in in IN cord-014597-66vd2mdu 37 10 the the DT cord-014597-66vd2mdu 37 11 KO KO NNP cord-014597-66vd2mdu 37 12 cell cell NN cord-014597-66vd2mdu 37 13 line line NN cord-014597-66vd2mdu 37 14 resulted result VBD cord-014597-66vd2mdu 37 15 in in IN cord-014597-66vd2mdu 37 16 no no DT cord-014597-66vd2mdu 37 17 / / SYM cord-014597-66vd2mdu 37 18 significantly significantly RB cord-014597-66vd2mdu 37 19 less less JJR cord-014597-66vd2mdu 37 20 clipping clip VBG cord-014597-66vd2mdu 37 21 ( ( -LRB- cord-014597-66vd2mdu 37 22 Fig Fig NNP cord-014597-66vd2mdu 37 23 . . . cord-014597-66vd2mdu 37 24 1e 1e LS cord-014597-66vd2mdu 37 25 ) ) -RRB- cord-014597-66vd2mdu 37 26 . . . cord-014597-66vd2mdu 38 1 The the DT cord-014597-66vd2mdu 38 2 protein protein NN cord-014597-66vd2mdu 38 3 titer titer NN cord-014597-66vd2mdu 38 4 and and CC cord-014597-66vd2mdu 38 5 the the DT cord-014597-66vd2mdu 38 6 cell cell NN cord-014597-66vd2mdu 38 7 growth growth NN cord-014597-66vd2mdu 38 8 behaviour behaviour NN cord-014597-66vd2mdu 38 9 of of IN cord-014597-66vd2mdu 38 10 the the DT cord-014597-66vd2mdu 38 11 matriptase matriptase NNP cord-014597-66vd2mdu 38 12 KO KO NNP cord-014597-66vd2mdu 38 13 cells cell NNS cord-014597-66vd2mdu 38 14 were be VBD cord-014597-66vd2mdu 38 15 similar similar JJ cord-014597-66vd2mdu 38 16 to to IN cord-014597-66vd2mdu 38 17 the the DT cord-014597-66vd2mdu 38 18 corresponding correspond VBG cord-014597-66vd2mdu 38 19 wildtype wildtype NN cord-014597-66vd2mdu 38 20 ( ( -LRB- cord-014597-66vd2mdu 38 21 wt wt NN cord-014597-66vd2mdu 38 22 ) ) -RRB- cord-014597-66vd2mdu 38 23 cells cell NNS cord-014597-66vd2mdu 38 24 ( ( -LRB- cord-014597-66vd2mdu 38 25 Fig Fig NNP cord-014597-66vd2mdu 38 26 . . . cord-014597-66vd2mdu 38 27 1d 1d LS cord-014597-66vd2mdu 38 28 ) ) -RRB- cord-014597-66vd2mdu 38 29 as as IN cord-014597-66vd2mdu 38 30 shown show VBN cord-014597-66vd2mdu 38 31 by by IN cord-014597-66vd2mdu 38 32 comparative comparative JJ cord-014597-66vd2mdu 38 33 cultivation cultivation NN cord-014597-66vd2mdu 38 34 in in IN cord-014597-66vd2mdu 38 35 AMBR AMBR NNP cord-014597-66vd2mdu 38 36 system system NN cord-014597-66vd2mdu 38 37 . . . cord-014597-66vd2mdu 39 1 Conclusions conclusion NNS cord-014597-66vd2mdu 40 1 One one CD cord-014597-66vd2mdu 40 2 major major JJ cord-014597-66vd2mdu 40 3 challenge challenge NN cord-014597-66vd2mdu 40 4 for for IN cord-014597-66vd2mdu 40 5 the the DT cord-014597-66vd2mdu 40 6 production production NN cord-014597-66vd2mdu 40 7 of of IN cord-014597-66vd2mdu 40 8 recombinant recombinant JJ cord-014597-66vd2mdu 40 9 proteins protein NNS cord-014597-66vd2mdu 40 10 is be VBZ cord-014597-66vd2mdu 40 11 CHO CHO NNP cord-014597-66vd2mdu 40 12 host host NN cord-014597-66vd2mdu 40 13 cell cell NN cord-014597-66vd2mdu 40 14 mediated mediate VBN cord-014597-66vd2mdu 40 15 proteolytic proteolytic JJ cord-014597-66vd2mdu 40 16 degradation degradation NN cord-014597-66vd2mdu 40 17 which which WDT cord-014597-66vd2mdu 40 18 can can MD cord-014597-66vd2mdu 40 19 negatively negatively RB cord-014597-66vd2mdu 40 20 impact impact VB cord-014597-66vd2mdu 40 21 or or CC cord-014597-66vd2mdu 40 22 even even RB cord-014597-66vd2mdu 40 23 result result VB cord-014597-66vd2mdu 40 24 in in IN cord-014597-66vd2mdu 40 25 termination termination NN cord-014597-66vd2mdu 40 26 of of IN cord-014597-66vd2mdu 40 27 projects project NNS cord-014597-66vd2mdu 40 28 [ [ -LRB- cord-014597-66vd2mdu 40 29 2 2 CD cord-014597-66vd2mdu 40 30 ; ; : cord-014597-66vd2mdu 40 31 3 3 CD cord-014597-66vd2mdu 40 32 ] ] -RRB- cord-014597-66vd2mdu 40 33 . . . cord-014597-66vd2mdu 41 1 Using use VBG cord-014597-66vd2mdu 41 2 a a DT cord-014597-66vd2mdu 41 3 variety variety NN cord-014597-66vd2mdu 41 4 of of IN cord-014597-66vd2mdu 41 5 techniques technique NNS cord-014597-66vd2mdu 41 6 such such JJ cord-014597-66vd2mdu 41 7 as as IN cord-014597-66vd2mdu 41 8 applying apply VBG cord-014597-66vd2mdu 41 9 protease protease NN cord-014597-66vd2mdu 41 10 inhibitors inhibitor NNS cord-014597-66vd2mdu 41 11 , , , cord-014597-66vd2mdu 41 12 transcriptomics transcriptomics NNP cord-014597-66vd2mdu 41 13 and and CC cord-014597-66vd2mdu 41 14 siRNA siRNA NNP cord-014597-66vd2mdu 41 15 mediated mediate VBD cord-014597-66vd2mdu 41 16 knock knock NN cord-014597-66vd2mdu 41 17 - - HYPH cord-014597-66vd2mdu 41 18 down down RP cord-014597-66vd2mdu 41 19 we -PRON- PRP cord-014597-66vd2mdu 41 20 were be VBD cord-014597-66vd2mdu 41 21 able able JJ cord-014597-66vd2mdu 41 22 to to TO cord-014597-66vd2mdu 41 23 identify identify VB cord-014597-66vd2mdu 41 24 " " `` cord-014597-66vd2mdu 41 25 matriptase matriptase VB cord-014597-66vd2mdu 41 26 " " '' cord-014597-66vd2mdu 41 27 as as IN cord-014597-66vd2mdu 41 28 the the DT cord-014597-66vd2mdu 41 29 major major JJ cord-014597-66vd2mdu 41 30 protease protease NN cord-014597-66vd2mdu 41 31 involved involve VBN cord-014597-66vd2mdu 41 32 in in IN cord-014597-66vd2mdu 41 33 degradation degradation NN cord-014597-66vd2mdu 41 34 of of IN cord-014597-66vd2mdu 41 35 recombinant recombinant JJ cord-014597-66vd2mdu 41 36 proteins protein NNS cord-014597-66vd2mdu 41 37 expressed express VBN cord-014597-66vd2mdu 41 38 in in IN cord-014597-66vd2mdu 41 39 CHO CHO NNP cord-014597-66vd2mdu 41 40 - - HYPH cord-014597-66vd2mdu 41 41 K1 K1 NNP cord-014597-66vd2mdu 41 42 cells cell NNS cord-014597-66vd2mdu 41 43 . . . cord-014597-66vd2mdu 42 1 Subsequently subsequently RB cord-014597-66vd2mdu 42 2 we -PRON- PRP cord-014597-66vd2mdu 42 3 generated generate VBD cord-014597-66vd2mdu 42 4 a a DT cord-014597-66vd2mdu 42 5 matriptase matriptase JJ cord-014597-66vd2mdu 42 6 deficient deficient JJ cord-014597-66vd2mdu 42 7 CHO CHO NNP cord-014597-66vd2mdu 42 8 cell cell NN cord-014597-66vd2mdu 42 9 line line NN cord-014597-66vd2mdu 42 10 . . . cord-014597-66vd2mdu 43 1 Protein protein NN cord-014597-66vd2mdu 43 2 candidates candidate NNS cord-014597-66vd2mdu 43 3 of of IN cord-014597-66vd2mdu 43 4 diverse diverse JJ cord-014597-66vd2mdu 43 5 formats format NNS cord-014597-66vd2mdu 43 6 , , , cord-014597-66vd2mdu 43 7 severely severely RB cord-014597-66vd2mdu 43 8 degraded degrade VBN cord-014597-66vd2mdu 43 9 in in IN cord-014597-66vd2mdu 43 10 wt wt NN cord-014597-66vd2mdu 43 11 CHO CHO NNP cord-014597-66vd2mdu 43 12 - - HYPH cord-014597-66vd2mdu 43 13 K1 K1 NNP cord-014597-66vd2mdu 43 14 cell cell NN cord-014597-66vd2mdu 43 15 line line NN cord-014597-66vd2mdu 43 16 , , , cord-014597-66vd2mdu 43 17 were be VBD cord-014597-66vd2mdu 43 18 not not RB cord-014597-66vd2mdu 43 19 or or CC cord-014597-66vd2mdu 43 20 significantly significantly RB cord-014597-66vd2mdu 43 21 less less RBR cord-014597-66vd2mdu 43 22 cleaved cleave VBN cord-014597-66vd2mdu 43 23 in in IN cord-014597-66vd2mdu 43 24 the the DT cord-014597-66vd2mdu 43 25 matriptase matriptase NN cord-014597-66vd2mdu 43 26 KO KO NNP cord-014597-66vd2mdu 43 27 cell cell NN cord-014597-66vd2mdu 43 28 line line NN cord-014597-66vd2mdu 43 29 . . . cord-014597-66vd2mdu 44 1 Furthermore furthermore RB cord-014597-66vd2mdu 44 2 cell cell NN cord-014597-66vd2mdu 44 3 growth growth NN cord-014597-66vd2mdu 44 4 , , , cord-014597-66vd2mdu 44 5 viability viability NN cord-014597-66vd2mdu 44 6 and and CC cord-014597-66vd2mdu 44 7 productivity productivity NN cord-014597-66vd2mdu 44 8 levels level NNS cord-014597-66vd2mdu 44 9 were be VBD cord-014597-66vd2mdu 44 10 comparable comparable JJ cord-014597-66vd2mdu 44 11 between between IN cord-014597-66vd2mdu 44 12 the the DT cord-014597-66vd2mdu 44 13 wt wt NN cord-014597-66vd2mdu 44 14 and and CC cord-014597-66vd2mdu 44 15 the the DT cord-014597-66vd2mdu 44 16 matriptase matriptase NNP cord-014597-66vd2mdu 44 17 KO KO NNP cord-014597-66vd2mdu 44 18 cell cell NN cord-014597-66vd2mdu 44 19 line line NN cord-014597-66vd2mdu 44 20 . . . cord-014597-66vd2mdu 45 1 In in IN cord-014597-66vd2mdu 45 2 summary summary NN cord-014597-66vd2mdu 45 3 , , , cord-014597-66vd2mdu 45 4 we -PRON- PRP cord-014597-66vd2mdu 45 5 have have VBP cord-014597-66vd2mdu 45 6 generated generate VBN cord-014597-66vd2mdu 45 7 a a DT cord-014597-66vd2mdu 45 8 superior superior JJ cord-014597-66vd2mdu 45 9 platform platform NN cord-014597-66vd2mdu 45 10 - - HYPH cord-014597-66vd2mdu 45 11 compatible compatible JJ cord-014597-66vd2mdu 45 12 CHO CHO NNP cord-014597-66vd2mdu 45 13 production production NN cord-014597-66vd2mdu 45 14 host host NN cord-014597-66vd2mdu 45 15 cell cell NN cord-014597-66vd2mdu 45 16 line line NN cord-014597-66vd2mdu 45 17 with with IN cord-014597-66vd2mdu 45 18 the the DT cord-014597-66vd2mdu 45 19 same same JJ cord-014597-66vd2mdu 45 20 favourable favourable JJ cord-014597-66vd2mdu 45 21 productivity productivity NN cord-014597-66vd2mdu 45 22 properties property NNS cord-014597-66vd2mdu 45 23 as as IN cord-014597-66vd2mdu 45 24 the the DT cord-014597-66vd2mdu 45 25 parental parental JJ cord-014597-66vd2mdu 45 26 host host NN cord-014597-66vd2mdu 45 27 cell cell NN cord-014597-66vd2mdu 45 28 line line NN cord-014597-66vd2mdu 45 29 [ [ -LRB- cord-014597-66vd2mdu 45 30 4 4 CD cord-014597-66vd2mdu 45 31 ; ; SYM cord-014597-66vd2mdu 45 32 6 6 CD cord-014597-66vd2mdu 45 33 ] ] -RRB- cord-014597-66vd2mdu 45 34 , , , cord-014597-66vd2mdu 45 35 allowing allow VBG cord-014597-66vd2mdu 45 36 expression expression NN cord-014597-66vd2mdu 45 37 of of IN cord-014597-66vd2mdu 45 38 complex complex JJ cord-014597-66vd2mdu 45 39 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 45 40 prone prone JJ cord-014597-66vd2mdu 45 41 to to IN cord-014597-66vd2mdu 45 42 clipping clip VBG cord-014597-66vd2mdu 45 43 . . . cord-014597-66vd2mdu 46 1 Background Background NNP cord-014597-66vd2mdu 46 2 CHO CHO NNP cord-014597-66vd2mdu 46 3 cell cell NN cord-014597-66vd2mdu 46 4 lines line NNS cord-014597-66vd2mdu 46 5 are be VBP cord-014597-66vd2mdu 46 6 common common JJ cord-014597-66vd2mdu 46 7 hosts host NNS cord-014597-66vd2mdu 46 8 for for IN cord-014597-66vd2mdu 46 9 the the DT cord-014597-66vd2mdu 46 10 production production NN cord-014597-66vd2mdu 46 11 of of IN cord-014597-66vd2mdu 46 12 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 46 13 proteins protein NNS cord-014597-66vd2mdu 46 14 . . . cord-014597-66vd2mdu 47 1 So so RB cord-014597-66vd2mdu 47 2 far far RB cord-014597-66vd2mdu 47 3 , , , cord-014597-66vd2mdu 47 4 considerable considerable JJ cord-014597-66vd2mdu 47 5 progress progress NN cord-014597-66vd2mdu 47 6 has have VBZ cord-014597-66vd2mdu 47 7 been be VBN cord-014597-66vd2mdu 47 8 made make VBN cord-014597-66vd2mdu 47 9 increasing increase VBG cord-014597-66vd2mdu 47 10 productivity productivity NN cord-014597-66vd2mdu 47 11 of of IN cord-014597-66vd2mdu 47 12 cell cell NN cord-014597-66vd2mdu 47 13 culture culture NN cord-014597-66vd2mdu 47 14 to to TO cord-014597-66vd2mdu 47 15 meet meet VB cord-014597-66vd2mdu 47 16 the the DT cord-014597-66vd2mdu 47 17 rapidly rapidly RB cord-014597-66vd2mdu 47 18 growing grow VBG cord-014597-66vd2mdu 47 19 demand demand NN cord-014597-66vd2mdu 47 20 for for IN cord-014597-66vd2mdu 47 21 antibody antibody NN cord-014597-66vd2mdu 47 22 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 47 23 through through IN cord-014597-66vd2mdu 47 24 increased increase VBN cord-014597-66vd2mdu 47 25 cell cell NN cord-014597-66vd2mdu 47 26 densities density NNS cord-014597-66vd2mdu 47 27 and and CC cord-014597-66vd2mdu 47 28 longer long JJR cord-014597-66vd2mdu 47 29 culture culture NN cord-014597-66vd2mdu 47 30 times time NNS cord-014597-66vd2mdu 47 31 . . . cord-014597-66vd2mdu 48 1 The the DT cord-014597-66vd2mdu 48 2 downside downside NN cord-014597-66vd2mdu 48 3 is be VBZ cord-014597-66vd2mdu 48 4 the the DT cord-014597-66vd2mdu 48 5 increase increase NN cord-014597-66vd2mdu 48 6 of of IN cord-014597-66vd2mdu 48 7 the the DT cord-014597-66vd2mdu 48 8 process process NN cord-014597-66vd2mdu 48 9 related relate VBN cord-014597-66vd2mdu 48 10 impurities impurity NNS cord-014597-66vd2mdu 48 11 , , , cord-014597-66vd2mdu 48 12 bringing bring VBG cord-014597-66vd2mdu 48 13 new new JJ cord-014597-66vd2mdu 48 14 challenges challenge NNS cord-014597-66vd2mdu 48 15 for for IN cord-014597-66vd2mdu 48 16 process process NN cord-014597-66vd2mdu 48 17 and and CC cord-014597-66vd2mdu 48 18 harvest harvest NN cord-014597-66vd2mdu 48 19 development development NN cord-014597-66vd2mdu 48 20 . . . cord-014597-66vd2mdu 49 1 Among among IN cord-014597-66vd2mdu 49 2 the the DT cord-014597-66vd2mdu 49 3 process process NN cord-014597-66vd2mdu 49 4 related relate VBN cord-014597-66vd2mdu 49 5 impurities impurity NNS cord-014597-66vd2mdu 49 6 such such JJ cord-014597-66vd2mdu 49 7 as as IN cord-014597-66vd2mdu 49 8 host host NN cord-014597-66vd2mdu 49 9 cell cell NN cord-014597-66vd2mdu 49 10 proteins protein NNS cord-014597-66vd2mdu 49 11 ( ( -LRB- cord-014597-66vd2mdu 49 12 HCPs HCPs NNP cord-014597-66vd2mdu 49 13 ) ) -RRB- cord-014597-66vd2mdu 49 14 or or CC cord-014597-66vd2mdu 49 15 DNA dna VB cord-014597-66vd2mdu 49 16 the the DT cord-014597-66vd2mdu 49 17 potential potential JJ cord-014597-66vd2mdu 49 18 impact impact NN cord-014597-66vd2mdu 49 19 of of IN cord-014597-66vd2mdu 49 20 lipids lipid NNS cord-014597-66vd2mdu 49 21 production production NN cord-014597-66vd2mdu 49 22 and and CC cord-014597-66vd2mdu 49 23 release release NN cord-014597-66vd2mdu 49 24 during during IN cord-014597-66vd2mdu 49 25 cell cell NN cord-014597-66vd2mdu 49 26 culture culture NN cord-014597-66vd2mdu 49 27 is be VBZ cord-014597-66vd2mdu 49 28 still still RB cord-014597-66vd2mdu 49 29 poorly poorly RB cord-014597-66vd2mdu 49 30 understood understand VBN cord-014597-66vd2mdu 49 31 due due IN cord-014597-66vd2mdu 49 32 to to IN cord-014597-66vd2mdu 49 33 the the DT cord-014597-66vd2mdu 49 34 complex complex JJ cord-014597-66vd2mdu 49 35 nature nature NN cord-014597-66vd2mdu 49 36 and and CC cord-014597-66vd2mdu 49 37 diversity diversity NN cord-014597-66vd2mdu 49 38 of of IN cord-014597-66vd2mdu 49 39 this this DT cord-014597-66vd2mdu 49 40 class class NN cord-014597-66vd2mdu 49 41 of of IN cord-014597-66vd2mdu 49 42 molecules molecule NNS cord-014597-66vd2mdu 49 43 . . . cord-014597-66vd2mdu 50 1 Thanks thank NNS cord-014597-66vd2mdu 50 2 to to IN cord-014597-66vd2mdu 50 3 recent recent JJ cord-014597-66vd2mdu 50 4 advances advance NNS cord-014597-66vd2mdu 50 5 in in IN cord-014597-66vd2mdu 50 6 analytical analytical JJ cord-014597-66vd2mdu 50 7 tools tool NNS cord-014597-66vd2mdu 50 8 especially especially RB cord-014597-66vd2mdu 50 9 mass mass JJ cord-014597-66vd2mdu 50 10 spectrometry spectrometry NN cord-014597-66vd2mdu 50 11 , , , cord-014597-66vd2mdu 50 12 the the DT cord-014597-66vd2mdu 50 13 advent advent NN cord-014597-66vd2mdu 50 14 of of IN cord-014597-66vd2mdu 50 15 lipidomics lipidomics NNP cord-014597-66vd2mdu 50 16 offers offer VBZ cord-014597-66vd2mdu 50 17 now now RB cord-014597-66vd2mdu 50 18 the the DT cord-014597-66vd2mdu 50 19 feasibility feasibility NN cord-014597-66vd2mdu 50 20 to to TO cord-014597-66vd2mdu 50 21 study study VB cord-014597-66vd2mdu 50 22 several several JJ cord-014597-66vd2mdu 50 23 thousands thousand NNS cord-014597-66vd2mdu 50 24 of of IN cord-014597-66vd2mdu 50 25 lipid lipid NN cord-014597-66vd2mdu 50 26 species specie NNS cord-014597-66vd2mdu 50 27 thus thus RB cord-014597-66vd2mdu 50 28 unraveling unravel VBG cord-014597-66vd2mdu 50 29 the the DT cord-014597-66vd2mdu 50 30 possibility possibility NN cord-014597-66vd2mdu 50 31 to to TO cord-014597-66vd2mdu 50 32 understand understand VB cord-014597-66vd2mdu 50 33 and and CC cord-014597-66vd2mdu 50 34 potentially potentially RB cord-014597-66vd2mdu 50 35 control control VB cord-014597-66vd2mdu 50 36 the the DT cord-014597-66vd2mdu 50 37 interactions interaction NNS cord-014597-66vd2mdu 50 38 between between IN cord-014597-66vd2mdu 50 39 high high JJ cord-014597-66vd2mdu 50 40 performance performance NN cord-014597-66vd2mdu 50 41 bioreactor bioreactor NN cord-014597-66vd2mdu 50 42 processes process NNS cord-014597-66vd2mdu 50 43 , , , cord-014597-66vd2mdu 50 44 harvest harvest NN cord-014597-66vd2mdu 50 45 conditions condition NNS cord-014597-66vd2mdu 50 46 and and CC cord-014597-66vd2mdu 50 47 purification purification NN cord-014597-66vd2mdu 50 48 . . . cord-014597-66vd2mdu 51 1 In in IN cord-014597-66vd2mdu 51 2 order order NN cord-014597-66vd2mdu 51 3 to to TO cord-014597-66vd2mdu 51 4 analyze analyze VB cord-014597-66vd2mdu 51 5 and and CC cord-014597-66vd2mdu 51 6 quantify quantify VB cord-014597-66vd2mdu 51 7 lipids lipid NNS cord-014597-66vd2mdu 51 8 , , , cord-014597-66vd2mdu 51 9 we -PRON- PRP cord-014597-66vd2mdu 51 10 developed develop VBD cord-014597-66vd2mdu 51 11 a a DT cord-014597-66vd2mdu 51 12 three three CD cord-014597-66vd2mdu 51 13 steps step NNS cord-014597-66vd2mdu 51 14 method method NN cord-014597-66vd2mdu 51 15 . . . cord-014597-66vd2mdu 52 1 In in IN cord-014597-66vd2mdu 52 2 a a DT cord-014597-66vd2mdu 52 3 first first JJ cord-014597-66vd2mdu 52 4 step step NN cord-014597-66vd2mdu 52 5 , , , cord-014597-66vd2mdu 52 6 lipids lipid NNS cord-014597-66vd2mdu 52 7 were be VBD cord-014597-66vd2mdu 52 8 extracted extract VBN cord-014597-66vd2mdu 52 9 with with IN cord-014597-66vd2mdu 52 10 Methyl Methyl NNP cord-014597-66vd2mdu 52 11 tert tert NN cord-014597-66vd2mdu 52 12 - - HYPH cord-014597-66vd2mdu 52 13 butyl butyl NN cord-014597-66vd2mdu 52 14 ether ether NN cord-014597-66vd2mdu 52 15 ( ( -LRB- cord-014597-66vd2mdu 52 16 MTBE MTBE NNP cord-014597-66vd2mdu 52 17 ) ) -RRB- cord-014597-66vd2mdu 52 18 according accord VBG cord-014597-66vd2mdu 52 19 to to IN cord-014597-66vd2mdu 52 20 Matyash Matyash NNP cord-014597-66vd2mdu 52 21 method method NN cord-014597-66vd2mdu 52 22 [ [ -LRB- cord-014597-66vd2mdu 52 23 1 1 CD cord-014597-66vd2mdu 52 24 ] ] -RRB- cord-014597-66vd2mdu 52 25 . . . cord-014597-66vd2mdu 53 1 Lipids lipid NNS cord-014597-66vd2mdu 53 2 were be VBD cord-014597-66vd2mdu 53 3 then then RB cord-014597-66vd2mdu 53 4 separated separate VBN cord-014597-66vd2mdu 53 5 by by IN cord-014597-66vd2mdu 53 6 liquid liquid JJ cord-014597-66vd2mdu 53 7 chromatography chromatography NN cord-014597-66vd2mdu 53 8 using use VBG cord-014597-66vd2mdu 53 9 either either CC cord-014597-66vd2mdu 53 10 HILIC HILIC NNP cord-014597-66vd2mdu 53 11 of of IN cord-014597-66vd2mdu 53 12 reverse reverse JJ cord-014597-66vd2mdu 53 13 phase phase NN cord-014597-66vd2mdu 53 14 column column NN cord-014597-66vd2mdu 53 15 prior prior RB cord-014597-66vd2mdu 53 16 to to IN cord-014597-66vd2mdu 53 17 detection detection NN cord-014597-66vd2mdu 53 18 and and CC cord-014597-66vd2mdu 53 19 quantification quantification NN cord-014597-66vd2mdu 53 20 by by IN cord-014597-66vd2mdu 53 21 mass mass NN cord-014597-66vd2mdu 53 22 spectrometry spectrometry NN cord-014597-66vd2mdu 53 23 . . . cord-014597-66vd2mdu 54 1 All all DT cord-014597-66vd2mdu 54 2 lipid lipid NN cord-014597-66vd2mdu 54 3 classes class NNS cord-014597-66vd2mdu 54 4 were be VBD cord-014597-66vd2mdu 54 5 detected detect VBN cord-014597-66vd2mdu 54 6 by by IN cord-014597-66vd2mdu 54 7 ESI ESI NNP cord-014597-66vd2mdu 54 8 - - HYPH cord-014597-66vd2mdu 54 9 MS MS NNP cord-014597-66vd2mdu 54 10 / / SYM cord-014597-66vd2mdu 54 11 MS MS NNP cord-014597-66vd2mdu 54 12 excepted except VBD cord-014597-66vd2mdu 54 13 cholesterol cholesterol NN cord-014597-66vd2mdu 54 14 ( ( -LRB- cord-014597-66vd2mdu 54 15 APCI APCI NNP cord-014597-66vd2mdu 54 16 - - HYPH cord-014597-66vd2mdu 54 17 MS MS NNP cord-014597-66vd2mdu 54 18 / / SYM cord-014597-66vd2mdu 54 19 MS MS NNP cord-014597-66vd2mdu 54 20 ) ) -RRB- cord-014597-66vd2mdu 54 21 . . . cord-014597-66vd2mdu 55 1 Finally finally RB cord-014597-66vd2mdu 55 2 we -PRON- PRP cord-014597-66vd2mdu 55 3 applied apply VBD cord-014597-66vd2mdu 55 4 this this DT cord-014597-66vd2mdu 55 5 method method NN cord-014597-66vd2mdu 55 6 to to TO cord-014597-66vd2mdu 55 7 analyze analyze VB cord-014597-66vd2mdu 55 8 the the DT cord-014597-66vd2mdu 55 9 lipid lipid NN cord-014597-66vd2mdu 55 10 content content NN cord-014597-66vd2mdu 55 11 of of IN cord-014597-66vd2mdu 55 12 different different JJ cord-014597-66vd2mdu 55 13 cell cell NN cord-014597-66vd2mdu 55 14 lines line NNS cord-014597-66vd2mdu 55 15 each each DT cord-014597-66vd2mdu 55 16 expressing express VBG cord-014597-66vd2mdu 55 17 a a DT cord-014597-66vd2mdu 55 18 different different JJ cord-014597-66vd2mdu 55 19 recombinant recombinant JJ cord-014597-66vd2mdu 55 20 protein protein NN cord-014597-66vd2mdu 55 21 , , , cord-014597-66vd2mdu 55 22 during during IN cord-014597-66vd2mdu 55 23 a a DT cord-014597-66vd2mdu 55 24 14 14 CD cord-014597-66vd2mdu 55 25 days day NNS cord-014597-66vd2mdu 55 26 fed feed VBN cord-014597-66vd2mdu 55 27 batch batch NN cord-014597-66vd2mdu 55 28 process process NN cord-014597-66vd2mdu 55 29 . . . cord-014597-66vd2mdu 56 1 Lipid lipid NN cord-014597-66vd2mdu 56 2 from from IN cord-014597-66vd2mdu 56 3 CHO CHO NNP cord-014597-66vd2mdu 56 4 cells cell NNS cord-014597-66vd2mdu 56 5 were be VBD cord-014597-66vd2mdu 56 6 successfully successfully RB cord-014597-66vd2mdu 56 7 extracted extract VBN cord-014597-66vd2mdu 56 8 with with IN cord-014597-66vd2mdu 56 9 a a DT cord-014597-66vd2mdu 56 10 yield yield NN cord-014597-66vd2mdu 56 11 between between IN cord-014597-66vd2mdu 56 12 80 80 CD cord-014597-66vd2mdu 56 13 % % NN cord-014597-66vd2mdu 56 14 and and CC cord-014597-66vd2mdu 56 15 95 95 CD cord-014597-66vd2mdu 56 16 % % NN cord-014597-66vd2mdu 56 17 depending depend VBG cord-014597-66vd2mdu 56 18 on on IN cord-014597-66vd2mdu 56 19 the the DT cord-014597-66vd2mdu 56 20 different different JJ cord-014597-66vd2mdu 56 21 lipid lipid NN cord-014597-66vd2mdu 56 22 classes class NNS cord-014597-66vd2mdu 56 23 . . . cord-014597-66vd2mdu 57 1 Stable stable JJ cord-014597-66vd2mdu 57 2 isotope isotope NN cord-014597-66vd2mdu 57 3 labeled label VBN cord-014597-66vd2mdu 57 4 lipids lipid NNS cord-014597-66vd2mdu 57 5 were be VBD cord-014597-66vd2mdu 57 6 used use VBN cord-014597-66vd2mdu 57 7 as as IN cord-014597-66vd2mdu 57 8 internal internal JJ cord-014597-66vd2mdu 57 9 standard standard NN cord-014597-66vd2mdu 57 10 in in IN cord-014597-66vd2mdu 57 11 order order NN cord-014597-66vd2mdu 57 12 to to TO cord-014597-66vd2mdu 57 13 have have VB cord-014597-66vd2mdu 57 14 comparable comparable JJ cord-014597-66vd2mdu 57 15 results result NNS cord-014597-66vd2mdu 57 16 between between IN cord-014597-66vd2mdu 57 17 batches batch NNS cord-014597-66vd2mdu 57 18 . . . cord-014597-66vd2mdu 58 1 The the DT cord-014597-66vd2mdu 58 2 obtained obtain VBN cord-014597-66vd2mdu 58 3 results result NNS cord-014597-66vd2mdu 58 4 ( ( -LRB- cord-014597-66vd2mdu 58 5 Fig fig NN cord-014597-66vd2mdu 58 6 . . . cord-014597-66vd2mdu 58 7 1 1 LS cord-014597-66vd2mdu 58 8 ) ) -RRB- cord-014597-66vd2mdu 58 9 show show VBP cord-014597-66vd2mdu 58 10 that that IN cord-014597-66vd2mdu 58 11 for for IN cord-014597-66vd2mdu 58 12 a a DT cord-014597-66vd2mdu 58 13 given give VBN cord-014597-66vd2mdu 58 14 cell cell NN cord-014597-66vd2mdu 58 15 line line NN cord-014597-66vd2mdu 58 16 , , , cord-014597-66vd2mdu 58 17 lipid lipid NN cord-014597-66vd2mdu 58 18 distribution distribution NN cord-014597-66vd2mdu 58 19 is be VBZ cord-014597-66vd2mdu 58 20 changing change VBG cord-014597-66vd2mdu 58 21 over over IN cord-014597-66vd2mdu 58 22 the the DT cord-014597-66vd2mdu 58 23 process process NN cord-014597-66vd2mdu 58 24 . . . cord-014597-66vd2mdu 59 1 Moreover moreover RB cord-014597-66vd2mdu 59 2 , , , cord-014597-66vd2mdu 59 3 this this DT cord-014597-66vd2mdu 59 4 distribution distribution NN cord-014597-66vd2mdu 59 5 may may MD cord-014597-66vd2mdu 59 6 vary vary VB cord-014597-66vd2mdu 59 7 significantly significantly RB cord-014597-66vd2mdu 59 8 depending depend VBG cord-014597-66vd2mdu 59 9 on on IN cord-014597-66vd2mdu 59 10 the the DT cord-014597-66vd2mdu 59 11 cell cell NN cord-014597-66vd2mdu 59 12 line line NN cord-014597-66vd2mdu 59 13 : : : cord-014597-66vd2mdu 60 1 CL-1 CL-1 NNP cord-014597-66vd2mdu 60 2 and and CC cord-014597-66vd2mdu 60 3 in in IN cord-014597-66vd2mdu 60 4 a a DT cord-014597-66vd2mdu 60 5 lower low JJR cord-014597-66vd2mdu 60 6 extend extend NN cord-014597-66vd2mdu 60 7 , , , cord-014597-66vd2mdu 60 8 CL-3 CL-3 NNP cord-014597-66vd2mdu 60 9 , , , cord-014597-66vd2mdu 60 10 show show VBP cord-014597-66vd2mdu 60 11 an an DT cord-014597-66vd2mdu 60 12 accumulation accumulation NN cord-014597-66vd2mdu 60 13 of of IN cord-014597-66vd2mdu 60 14 triglycerides triglyceride NNS cord-014597-66vd2mdu 60 15 from from IN cord-014597-66vd2mdu 60 16 day day NN cord-014597-66vd2mdu 60 17 6 6 CD cord-014597-66vd2mdu 60 18 to to IN cord-014597-66vd2mdu 60 19 the the DT cord-014597-66vd2mdu 60 20 end end NN cord-014597-66vd2mdu 60 21 of of IN cord-014597-66vd2mdu 60 22 the the DT cord-014597-66vd2mdu 60 23 process process NN cord-014597-66vd2mdu 60 24 , , , cord-014597-66vd2mdu 60 25 while while IN cord-014597-66vd2mdu 60 26 CL-2 CL-2 NNP cord-014597-66vd2mdu 60 27 does do VBZ cord-014597-66vd2mdu 60 28 n't not RB cord-014597-66vd2mdu 60 29 seems seem VBZ cord-014597-66vd2mdu 60 30 to to TO cord-014597-66vd2mdu 60 31 follow follow VB cord-014597-66vd2mdu 60 32 this this DT cord-014597-66vd2mdu 60 33 trend trend NN cord-014597-66vd2mdu 60 34 . . . cord-014597-66vd2mdu 61 1 Conclusion conclusion NN cord-014597-66vd2mdu 61 2 Interestingly interestingly RB cord-014597-66vd2mdu 61 3 , , , cord-014597-66vd2mdu 61 4 in in IN cord-014597-66vd2mdu 61 5 some some DT cord-014597-66vd2mdu 61 6 cell cell NN cord-014597-66vd2mdu 61 7 lines line NNS cord-014597-66vd2mdu 61 8 / / SYM cord-014597-66vd2mdu 61 9 experimental experimental JJ cord-014597-66vd2mdu 61 10 conditions condition NNS cord-014597-66vd2mdu 61 11 , , , cord-014597-66vd2mdu 61 12 we -PRON- PRP cord-014597-66vd2mdu 61 13 highlighted highlight VBD cord-014597-66vd2mdu 61 14 an an DT cord-014597-66vd2mdu 61 15 overproduction overproduction NN cord-014597-66vd2mdu 61 16 of of IN cord-014597-66vd2mdu 61 17 triglycerides triglyceride NNS cord-014597-66vd2mdu 61 18 and and CC cord-014597-66vd2mdu 61 19 cholesterol cholesterol NN cord-014597-66vd2mdu 61 20 leading lead VBG cord-014597-66vd2mdu 61 21 to to IN cord-014597-66vd2mdu 61 22 the the DT cord-014597-66vd2mdu 61 23 accumulation accumulation NN cord-014597-66vd2mdu 61 24 of of IN cord-014597-66vd2mdu 61 25 lipid lipid NN cord-014597-66vd2mdu 61 26 droplets droplet NNS cord-014597-66vd2mdu 61 27 known know VBN cord-014597-66vd2mdu 61 28 as as IN cord-014597-66vd2mdu 61 29 energy energy NN cord-014597-66vd2mdu 61 30 storage storage NN cord-014597-66vd2mdu 61 31 sink sink NN cord-014597-66vd2mdu 61 32 . . . cord-014597-66vd2mdu 62 1 At at IN cord-014597-66vd2mdu 62 2 the the DT cord-014597-66vd2mdu 62 3 metabolic metabolic JJ cord-014597-66vd2mdu 62 4 level level NN cord-014597-66vd2mdu 62 5 , , , cord-014597-66vd2mdu 62 6 these these DT cord-014597-66vd2mdu 62 7 findings finding NNS cord-014597-66vd2mdu 62 8 suggest suggest VBP cord-014597-66vd2mdu 62 9 a a DT cord-014597-66vd2mdu 62 10 relative relative JJ cord-014597-66vd2mdu 62 11 overflow overflow NN cord-014597-66vd2mdu 62 12 of of IN cord-014597-66vd2mdu 62 13 the the DT cord-014597-66vd2mdu 62 14 carbon carbon NN cord-014597-66vd2mdu 62 15 metabolism metabolism NN cord-014597-66vd2mdu 62 16 . . . cord-014597-66vd2mdu 63 1 From from IN cord-014597-66vd2mdu 63 2 a a DT cord-014597-66vd2mdu 63 3 process process NN cord-014597-66vd2mdu 63 4 development development NN cord-014597-66vd2mdu 63 5 perspective perspective NN cord-014597-66vd2mdu 63 6 these these DT cord-014597-66vd2mdu 63 7 findings finding NNS cord-014597-66vd2mdu 63 8 can can MD cord-014597-66vd2mdu 63 9 be be VB cord-014597-66vd2mdu 63 10 considered consider VBN cord-014597-66vd2mdu 63 11 on on IN cord-014597-66vd2mdu 63 12 the the DT cord-014597-66vd2mdu 63 13 one one CD cord-014597-66vd2mdu 63 14 hand hand NN cord-014597-66vd2mdu 63 15 as as IN cord-014597-66vd2mdu 63 16 a a DT cord-014597-66vd2mdu 63 17 resource resource NN cord-014597-66vd2mdu 63 18 waste waste NN cord-014597-66vd2mdu 63 19 since since IN cord-014597-66vd2mdu 63 20 the the DT cord-014597-66vd2mdu 63 21 stored store VBN cord-014597-66vd2mdu 63 22 energy energy NN cord-014597-66vd2mdu 63 23 is be VBZ cord-014597-66vd2mdu 63 24 not not RB cord-014597-66vd2mdu 63 25 used use VBN cord-014597-66vd2mdu 63 26 for for IN cord-014597-66vd2mdu 63 27 protein protein NN cord-014597-66vd2mdu 63 28 / / SYM cord-014597-66vd2mdu 63 29 biomass biomass NN cord-014597-66vd2mdu 63 30 biosynthesis biosynthesis NN cord-014597-66vd2mdu 63 31 and and CC cord-014597-66vd2mdu 63 32 on on IN cord-014597-66vd2mdu 63 33 the the DT cord-014597-66vd2mdu 63 34 second second JJ cord-014597-66vd2mdu 63 35 hand hand NN cord-014597-66vd2mdu 63 36 as as IN cord-014597-66vd2mdu 63 37 the the DT cord-014597-66vd2mdu 63 38 root root NN cord-014597-66vd2mdu 63 39 cause cause NN cord-014597-66vd2mdu 63 40 of of IN cord-014597-66vd2mdu 63 41 additional additional JJ cord-014597-66vd2mdu 63 42 process process NN cord-014597-66vd2mdu 63 43 challenges challenge NNS cord-014597-66vd2mdu 63 44 especially especially RB cord-014597-66vd2mdu 63 45 during during IN cord-014597-66vd2mdu 63 46 the the DT cord-014597-66vd2mdu 63 47 harvest harvest NN cord-014597-66vd2mdu 63 48 and and CC cord-014597-66vd2mdu 63 49 the the DT cord-014597-66vd2mdu 63 50 first first JJ cord-014597-66vd2mdu 63 51 capture capture NN cord-014597-66vd2mdu 63 52 steps step NNS cord-014597-66vd2mdu 63 53 given give VBN cord-014597-66vd2mdu 63 54 the the DT cord-014597-66vd2mdu 63 55 hydrophobic hydrophobic JJ cord-014597-66vd2mdu 63 56 nature nature NN cord-014597-66vd2mdu 63 57 of of IN cord-014597-66vd2mdu 63 58 these these DT cord-014597-66vd2mdu 63 59 molecules molecule NNS cord-014597-66vd2mdu 63 60 . . . cord-014597-66vd2mdu 64 1 Implementation implementation NN cord-014597-66vd2mdu 64 2 of of IN cord-014597-66vd2mdu 64 3 lipidomics lipidomic NNS cord-014597-66vd2mdu 64 4 analysis analysis NN cord-014597-66vd2mdu 64 5 enables enable VBZ cord-014597-66vd2mdu 64 6 us -PRON- PRP cord-014597-66vd2mdu 64 7 to to TO cord-014597-66vd2mdu 64 8 highlight highlight VB cord-014597-66vd2mdu 64 9 a a DT cord-014597-66vd2mdu 64 10 new new JJ cord-014597-66vd2mdu 64 11 type type NN cord-014597-66vd2mdu 64 12 of of IN cord-014597-66vd2mdu 64 13 process process NN cord-014597-66vd2mdu 64 14 variability variability NN cord-014597-66vd2mdu 64 15 and and CC cord-014597-66vd2mdu 64 16 to to TO cord-014597-66vd2mdu 64 17 anticipate anticipate VB cord-014597-66vd2mdu 64 18 potential potential JJ cord-014597-66vd2mdu 64 19 problems problem NNS cord-014597-66vd2mdu 64 20 for for IN cord-014597-66vd2mdu 64 21 the the DT cord-014597-66vd2mdu 64 22 downstream downstream JJ cord-014597-66vd2mdu 64 23 steps step NNS cord-014597-66vd2mdu 64 24 . . . cord-014597-66vd2mdu 65 1 The the DT cord-014597-66vd2mdu 65 2 application application NN cord-014597-66vd2mdu 65 3 of of IN cord-014597-66vd2mdu 65 4 this this DT cord-014597-66vd2mdu 65 5 methodology methodology NN cord-014597-66vd2mdu 65 6 on on IN cord-014597-66vd2mdu 65 7 our -PRON- PRP$ cord-014597-66vd2mdu 65 8 platform platform NN cord-014597-66vd2mdu 65 9 has have VBZ cord-014597-66vd2mdu 65 10 helped help VBN cord-014597-66vd2mdu 65 11 us -PRON- PRP cord-014597-66vd2mdu 65 12 to to TO cord-014597-66vd2mdu 65 13 design design VB cord-014597-66vd2mdu 65 14 tailor tailor NN cord-014597-66vd2mdu 65 15 made make VBD cord-014597-66vd2mdu 65 16 solutions solution NNS cord-014597-66vd2mdu 65 17 ( ( -LRB- cord-014597-66vd2mdu 65 18 pretreatment pretreatment NN cord-014597-66vd2mdu 65 19 selection selection NN cord-014597-66vd2mdu 65 20 , , , cord-014597-66vd2mdu 65 21 filter filter NN cord-014597-66vd2mdu 65 22 selection selection NN cord-014597-66vd2mdu 65 23 , , , cord-014597-66vd2mdu 65 24 … … NFP cord-014597-66vd2mdu 65 25 ) ) -RRB- cord-014597-66vd2mdu 65 26 at at IN cord-014597-66vd2mdu 65 27 the the DT cord-014597-66vd2mdu 65 28 clarification clarification NN cord-014597-66vd2mdu 65 29 step step NN cord-014597-66vd2mdu 65 30 which which WDT cord-014597-66vd2mdu 65 31 are be VBP cord-014597-66vd2mdu 65 32 now now RB cord-014597-66vd2mdu 65 33 implemented implement VBN cord-014597-66vd2mdu 65 34 in in IN cord-014597-66vd2mdu 65 35 our -PRON- PRP$ cord-014597-66vd2mdu 65 36 harvest harvest NN cord-014597-66vd2mdu 65 37 development development NN cord-014597-66vd2mdu 65 38 platform platform NN cord-014597-66vd2mdu 65 39 approach approach NN cord-014597-66vd2mdu 65 40 . . . cord-014597-66vd2mdu 65 41 . . . cord-014597-66vd2mdu 66 1 Matriptase Matriptase NNP cord-014597-66vd2mdu 66 2 knock knock NN cord-014597-66vd2mdu 66 3 - - HYPH cord-014597-66vd2mdu 66 4 out out NN cord-014597-66vd2mdu 66 5 in in IN cord-014597-66vd2mdu 66 6 CHO CHO NNP cord-014597-66vd2mdu 66 7 cells cell NNS cord-014597-66vd2mdu 66 8 prevents prevent VBZ cord-014597-66vd2mdu 66 9 clipping clip VBG cord-014597-66vd2mdu 66 10 of of IN cord-014597-66vd2mdu 66 11 recombinant recombinant JJ cord-014597-66vd2mdu 66 12 proteins protein NNS cord-014597-66vd2mdu 66 13 . . . cord-014597-66vd2mdu 67 1 a a DT cord-014597-66vd2mdu 67 2 Serine Serine NNP cord-014597-66vd2mdu 67 3 protease protease NN cord-014597-66vd2mdu 67 4 inhibitors inhibitor NNS cord-014597-66vd2mdu 67 5 protect protect VBP cord-014597-66vd2mdu 67 6 model model NN cord-014597-66vd2mdu 67 7 mAb mab NN cord-014597-66vd2mdu 67 8 from from IN cord-014597-66vd2mdu 67 9 proteolytic proteolytic JJ cord-014597-66vd2mdu 67 10 degradation degradation NN cord-014597-66vd2mdu 67 11 in in IN cord-014597-66vd2mdu 67 12 CHO CHO NNP cord-014597-66vd2mdu 67 13 - - HYPH cord-014597-66vd2mdu 67 14 K1 K1 NNP cord-014597-66vd2mdu 67 15 cell cell NN cord-014597-66vd2mdu 67 16 derived derive VBN cord-014597-66vd2mdu 67 17 conditioned condition VBN cord-014597-66vd2mdu 67 18 medium medium NN cord-014597-66vd2mdu 67 19 . . . cord-014597-66vd2mdu 68 1 The the DT cord-014597-66vd2mdu 68 2 model model NN cord-014597-66vd2mdu 68 3 mAb mab NN cord-014597-66vd2mdu 68 4 was be VBD cord-014597-66vd2mdu 68 5 incubated incubate VBN cord-014597-66vd2mdu 68 6 in in IN cord-014597-66vd2mdu 68 7 conditioned condition VBN cord-014597-66vd2mdu 68 8 medium medium NN cord-014597-66vd2mdu 68 9 for for IN cord-014597-66vd2mdu 68 10 0h 0h CD cord-014597-66vd2mdu 68 11 or or CC cord-014597-66vd2mdu 68 12 48h 48h NNS cord-014597-66vd2mdu 68 13 at at IN cord-014597-66vd2mdu 68 14 37 37 CD cord-014597-66vd2mdu 68 15 ° ° NN cord-014597-66vd2mdu 68 16 C c NN cord-014597-66vd2mdu 68 17 , , , cord-014597-66vd2mdu 68 18 subsequently subsequently RB cord-014597-66vd2mdu 68 19 samples sample NNS cord-014597-66vd2mdu 68 20 were be VBD cord-014597-66vd2mdu 68 21 analyzed analyze VBN cord-014597-66vd2mdu 68 22 by by IN cord-014597-66vd2mdu 68 23 western western JJ cord-014597-66vd2mdu 68 24 blot blot NN cord-014597-66vd2mdu 68 25 . . . cord-014597-66vd2mdu 69 1 Broad broad JJ cord-014597-66vd2mdu 69 2 spectrum spectrum NN cord-014597-66vd2mdu 69 3 serine serine NN cord-014597-66vd2mdu 69 4 protease protease NN cord-014597-66vd2mdu 69 5 inhibitors inhibitor NNS cord-014597-66vd2mdu 69 6 ( ( -LRB- cord-014597-66vd2mdu 69 7 Aprotinin Aprotinin NNP cord-014597-66vd2mdu 69 8 , , , cord-014597-66vd2mdu 69 9 Leupetin Leupetin NNP cord-014597-66vd2mdu 69 10 ) ) -RRB- cord-014597-66vd2mdu 69 11 were be VBD cord-014597-66vd2mdu 69 12 added add VBN cord-014597-66vd2mdu 69 13 during during IN cord-014597-66vd2mdu 69 14 incubation incubation NN cord-014597-66vd2mdu 69 15 . . . cord-014597-66vd2mdu 70 1 Aprotinin Aprotinin NNP cord-014597-66vd2mdu 70 2 and and CC cord-014597-66vd2mdu 70 3 Leupetin Leupetin NNP cord-014597-66vd2mdu 70 4 are be VBP cord-014597-66vd2mdu 70 5 inhibiting inhibit VBG cord-014597-66vd2mdu 70 6 proteolytic proteolytic JJ cord-014597-66vd2mdu 70 7 degradation degradation NN cord-014597-66vd2mdu 70 8 . . . cord-014597-66vd2mdu 71 1 The the DT cord-014597-66vd2mdu 71 2 intact intact JJ cord-014597-66vd2mdu 71 3 mAb mab NN cord-014597-66vd2mdu 71 4 ( ( -LRB- cord-014597-66vd2mdu 71 5 upper upper JJ cord-014597-66vd2mdu 71 6 band band NN cord-014597-66vd2mdu 71 7 ) ) -RRB- cord-014597-66vd2mdu 71 8 and and CC cord-014597-66vd2mdu 71 9 the the DT cord-014597-66vd2mdu 71 10 clipped clip VBN cord-014597-66vd2mdu 71 11 mAb mAb NNS cord-014597-66vd2mdu 71 12 ( ( -LRB- cord-014597-66vd2mdu 71 13 lower low JJR cord-014597-66vd2mdu 71 14 band band NN cord-014597-66vd2mdu 71 15 ) ) -RRB- cord-014597-66vd2mdu 71 16 are be VBP cord-014597-66vd2mdu 71 17 indicated indicate VBN cord-014597-66vd2mdu 71 18 by by IN cord-014597-66vd2mdu 71 19 arrows arrow NNS cord-014597-66vd2mdu 71 20 . . . cord-014597-66vd2mdu 72 1 b b LS cord-014597-66vd2mdu 72 2 Gene gene NN cord-014597-66vd2mdu 72 3 expression expression NN cord-014597-66vd2mdu 72 4 profiling profiling NN cord-014597-66vd2mdu 72 5 of of IN cord-014597-66vd2mdu 72 6 CHO CHO NNP cord-014597-66vd2mdu 72 7 - - HYPH cord-014597-66vd2mdu 72 8 K1 K1 NNP cord-014597-66vd2mdu 72 9 versus versus IN cord-014597-66vd2mdu 72 10 CHO CHO NNP cord-014597-66vd2mdu 72 11 - - HYPH cord-014597-66vd2mdu 72 12 A A NNP cord-014597-66vd2mdu 72 13 by by IN cord-014597-66vd2mdu 72 14 NGS NGS NNP cord-014597-66vd2mdu 72 15 . . . cord-014597-66vd2mdu 73 1 Shown show VBN cord-014597-66vd2mdu 73 2 is be VBZ cord-014597-66vd2mdu 73 3 the the DT cord-014597-66vd2mdu 73 4 gene gene NN cord-014597-66vd2mdu 73 5 expression expression NN cord-014597-66vd2mdu 73 6 profile profile NN cord-014597-66vd2mdu 73 7 of of IN cord-014597-66vd2mdu 73 8 " " `` cord-014597-66vd2mdu 73 9 secreted secrete VBN cord-014597-66vd2mdu 73 10 / / SYM cord-014597-66vd2mdu 73 11 shedded shedde VBN cord-014597-66vd2mdu 73 12 members member NNS cord-014597-66vd2mdu 73 13 of of IN cord-014597-66vd2mdu 73 14 the the DT cord-014597-66vd2mdu 73 15 S1A s1a NN cord-014597-66vd2mdu 73 16 trypsin trypsin NN cord-014597-66vd2mdu 73 17 - - HYPH cord-014597-66vd2mdu 73 18 like like JJ cord-014597-66vd2mdu 73 19 serine serine NN cord-014597-66vd2mdu 73 20 protease protease NN cord-014597-66vd2mdu 73 21 family family NN cord-014597-66vd2mdu 73 22 " " '' cord-014597-66vd2mdu 73 23 for for IN cord-014597-66vd2mdu 73 24 CHO CHO NNP cord-014597-66vd2mdu 73 25 - - HYPH cord-014597-66vd2mdu 73 26 K1 K1 NNP cord-014597-66vd2mdu 73 27 and and CC cord-014597-66vd2mdu 73 28 CHO CHO NNP cord-014597-66vd2mdu 73 29 - - HYPH cord-014597-66vd2mdu 73 30 A a DT cord-014597-66vd2mdu 73 31 cell cell NN cord-014597-66vd2mdu 73 32 lines line NNS cord-014597-66vd2mdu 73 33 using use VBG cord-014597-66vd2mdu 73 34 next next JJ cord-014597-66vd2mdu 73 35 generation generation NN cord-014597-66vd2mdu 73 36 sequencing sequencing NN cord-014597-66vd2mdu 73 37 . . . cord-014597-66vd2mdu 74 1 The the DT cord-014597-66vd2mdu 74 2 gene gene NN cord-014597-66vd2mdu 74 3 expression expression NN cord-014597-66vd2mdu 74 4 analysis analysis NN cord-014597-66vd2mdu 74 5 highlights highlight NNS cord-014597-66vd2mdu 74 6 that that IN cord-014597-66vd2mdu 74 7 five five CD cord-014597-66vd2mdu 74 8 proteases protease NNS cord-014597-66vd2mdu 74 9 were be VBD cord-014597-66vd2mdu 74 10 more more JJR cord-014597-66vd2mdu 74 11 than than IN cord-014597-66vd2mdu 74 12 1.5 1.5 CD cord-014597-66vd2mdu 74 13 fold fold VB cord-014597-66vd2mdu 74 14 higher higher RBR cord-014597-66vd2mdu 74 15 expressed express VBN cord-014597-66vd2mdu 74 16 in in IN cord-014597-66vd2mdu 74 17 CHO CHO NNP cord-014597-66vd2mdu 74 18 - - HYPH cord-014597-66vd2mdu 74 19 K1 K1 NNP cord-014597-66vd2mdu 74 20 cells cell NNS cord-014597-66vd2mdu 74 21 ( ( -LRB- cord-014597-66vd2mdu 74 22 labelled label VBN cord-014597-66vd2mdu 74 23 with with IN cord-014597-66vd2mdu 74 24 a a DT cord-014597-66vd2mdu 74 25 red red JJ cord-014597-66vd2mdu 74 26 asterix asterix NN cord-014597-66vd2mdu 74 27 ) ) -RRB- cord-014597-66vd2mdu 74 28 . . . cord-014597-66vd2mdu 75 1 The the DT cord-014597-66vd2mdu 75 2 y y NN cord-014597-66vd2mdu 75 3 - - HYPH cord-014597-66vd2mdu 75 4 axis axis NN cord-014597-66vd2mdu 75 5 shows show VBZ cord-014597-66vd2mdu 75 6 the the DT cord-014597-66vd2mdu 75 7 transcript transcript NN cord-014597-66vd2mdu 75 8 abundance abundance NN cord-014597-66vd2mdu 75 9 as as IN cord-014597-66vd2mdu 75 10 RPKM RPKM NNP cord-014597-66vd2mdu 75 11 ( ( -LRB- cord-014597-66vd2mdu 75 12 Reads read VBZ cord-014597-66vd2mdu 75 13 Per per IN cord-014597-66vd2mdu 75 14 Kilobase Kilobase NNP cord-014597-66vd2mdu 75 15 of of IN cord-014597-66vd2mdu 75 16 exon exon NN cord-014597-66vd2mdu 75 17 model model NN cord-014597-66vd2mdu 75 18 per per IN cord-014597-66vd2mdu 75 19 Million million CD cord-014597-66vd2mdu 75 20 mapped map VBN cord-014597-66vd2mdu 75 21 reads read VBZ cord-014597-66vd2mdu 75 22 ) ) -RRB- cord-014597-66vd2mdu 75 23 . . . cord-014597-66vd2mdu 76 1 c c NNP cord-014597-66vd2mdu 76 2 siRNA siRNA NNP cord-014597-66vd2mdu 76 3 knock knock VB cord-014597-66vd2mdu 76 4 - - HYPH cord-014597-66vd2mdu 76 5 down down NN cord-014597-66vd2mdu 76 6 identifies identify VBZ cord-014597-66vd2mdu 76 7 matriptase matriptase NN cord-014597-66vd2mdu 76 8 as as IN cord-014597-66vd2mdu 76 9 major major JJ cord-014597-66vd2mdu 76 10 clipping clip VBG cord-014597-66vd2mdu 76 11 protease protease NN cord-014597-66vd2mdu 76 12 and and CC cord-014597-66vd2mdu 76 13 CHO CHO NNP cord-014597-66vd2mdu 76 14 matriptase matriptase NN cord-014597-66vd2mdu 76 15 KO KO NNP cord-014597-66vd2mdu 76 16 clone clone NN cord-014597-66vd2mdu 76 17 shows show VBZ cord-014597-66vd2mdu 76 18 no no DT cord-014597-66vd2mdu 76 19 detectable detectable JJ cord-014597-66vd2mdu 76 20 clipping clip VBG cord-014597-66vd2mdu 76 21 activity activity NN cord-014597-66vd2mdu 76 22 . . . cord-014597-66vd2mdu 77 1 Upper upper JJ cord-014597-66vd2mdu 77 2 figure figure NN cord-014597-66vd2mdu 77 3 : : : cord-014597-66vd2mdu 77 4 siRNAs siRNAs NNP cord-014597-66vd2mdu 77 5 directed direct VBN cord-014597-66vd2mdu 77 6 against against IN cord-014597-66vd2mdu 77 7 the the DT cord-014597-66vd2mdu 77 8 five five CD cord-014597-66vd2mdu 77 9 protease protease NN cord-014597-66vd2mdu 77 10 genes gene NNS cord-014597-66vd2mdu 77 11 and and CC cord-014597-66vd2mdu 77 12 scrambled scramble VBN cord-014597-66vd2mdu 77 13 ( ( -LRB- cord-014597-66vd2mdu 77 14 scr scr NNP cord-014597-66vd2mdu 77 15 . . . cord-014597-66vd2mdu 77 16 ) ) -RRB- cord-014597-66vd2mdu 78 1 siRNA siRNA NNP cord-014597-66vd2mdu 78 2 were be VBD cord-014597-66vd2mdu 78 3 transfected transfecte VBN cord-014597-66vd2mdu 78 4 and and CC cord-014597-66vd2mdu 78 5 conditioned condition VBN cord-014597-66vd2mdu 78 6 medium medium NN cord-014597-66vd2mdu 78 7 was be VBD cord-014597-66vd2mdu 78 8 collected collect VBN cord-014597-66vd2mdu 78 9 three three CD cord-014597-66vd2mdu 78 10 days day NNS cord-014597-66vd2mdu 78 11 after after IN cord-014597-66vd2mdu 78 12 transfection transfection NN cord-014597-66vd2mdu 78 13 . . . cord-014597-66vd2mdu 79 1 The the DT cord-014597-66vd2mdu 79 2 model model NN cord-014597-66vd2mdu 79 3 mAb mab NN cord-014597-66vd2mdu 79 4 was be VBD cord-014597-66vd2mdu 79 5 incubated incubate VBN cord-014597-66vd2mdu 79 6 in in IN cord-014597-66vd2mdu 79 7 fresh fresh JJ cord-014597-66vd2mdu 79 8 medium medium NN cord-014597-66vd2mdu 79 9 as as IN cord-014597-66vd2mdu 79 10 control control NN cord-014597-66vd2mdu 79 11 ( ( -LRB- cord-014597-66vd2mdu 79 12 first first JJ cord-014597-66vd2mdu 79 13 lane lane NN cord-014597-66vd2mdu 79 14 ) ) -RRB- cord-014597-66vd2mdu 79 15 and and CC cord-014597-66vd2mdu 79 16 conditioned condition VBN cord-014597-66vd2mdu 79 17 medium medium NN cord-014597-66vd2mdu 79 18 from from IN cord-014597-66vd2mdu 79 19 the the DT cord-014597-66vd2mdu 79 20 siRNA siRNA NNP cord-014597-66vd2mdu 79 21 transfected transfecte VBN cord-014597-66vd2mdu 79 22 cells cell NNS cord-014597-66vd2mdu 79 23 . . . cord-014597-66vd2mdu 80 1 Samples sample NNS cord-014597-66vd2mdu 80 2 were be VBD cord-014597-66vd2mdu 80 3 analyzed analyze VBN cord-014597-66vd2mdu 80 4 by by IN cord-014597-66vd2mdu 80 5 western western JJ cord-014597-66vd2mdu 80 6 blot blot NN cord-014597-66vd2mdu 80 7 . . . cord-014597-66vd2mdu 81 1 Only only RB cord-014597-66vd2mdu 81 2 siRNA siRNA NNP cord-014597-66vd2mdu 81 3 targeting target VBG cord-014597-66vd2mdu 81 4 matriptase matriptase NNP cord-014597-66vd2mdu 81 5 ( ( -LRB- cord-014597-66vd2mdu 81 6 ST14 ST14 NNP cord-014597-66vd2mdu 81 7 ) ) -RRB- cord-014597-66vd2mdu 81 8 showed show VBD cord-014597-66vd2mdu 81 9 reduced reduce VBN cord-014597-66vd2mdu 81 10 proteolytic proteolytic JJ cord-014597-66vd2mdu 81 11 degradation degradation NN cord-014597-66vd2mdu 81 12 . . . cord-014597-66vd2mdu 82 1 The the DT cord-014597-66vd2mdu 82 2 intact intact JJ cord-014597-66vd2mdu 82 3 mAb mab NN cord-014597-66vd2mdu 82 4 ( ( -LRB- cord-014597-66vd2mdu 82 5 upper upper JJ cord-014597-66vd2mdu 82 6 band band NN cord-014597-66vd2mdu 82 7 ) ) -RRB- cord-014597-66vd2mdu 82 8 and and CC cord-014597-66vd2mdu 82 9 the the DT cord-014597-66vd2mdu 82 10 clipped clip VBN cord-014597-66vd2mdu 82 11 mAb mAb NNS cord-014597-66vd2mdu 82 12 ( ( -LRB- cord-014597-66vd2mdu 82 13 lower low JJR cord-014597-66vd2mdu 82 14 band band NN cord-014597-66vd2mdu 82 15 ) ) -RRB- cord-014597-66vd2mdu 82 16 are be VBP cord-014597-66vd2mdu 82 17 indicated indicate VBN cord-014597-66vd2mdu 82 18 by by IN cord-014597-66vd2mdu 82 19 arrows arrow NNS cord-014597-66vd2mdu 82 20 . . . cord-014597-66vd2mdu 83 1 Lower low JJR cord-014597-66vd2mdu 83 2 figure figure NN cord-014597-66vd2mdu 84 1 : : : cord-014597-66vd2mdu 84 2 The the DT cord-014597-66vd2mdu 84 3 model model NN cord-014597-66vd2mdu 84 4 mAb mab NN cord-014597-66vd2mdu 84 5 was be VBD cord-014597-66vd2mdu 84 6 incubated incubate VBN cord-014597-66vd2mdu 84 7 for for IN cord-014597-66vd2mdu 84 8 48h 48h NNS cord-014597-66vd2mdu 84 9 in in IN cord-014597-66vd2mdu 84 10 conditioned condition VBN cord-014597-66vd2mdu 84 11 medium medium NN cord-014597-66vd2mdu 84 12 collected collect VBN cord-014597-66vd2mdu 84 13 from from IN cord-014597-66vd2mdu 84 14 wt wt NNP cord-014597-66vd2mdu 84 15 CHO CHO NNP cord-014597-66vd2mdu 84 16 - - HYPH cord-014597-66vd2mdu 84 17 K1 K1 NNP cord-014597-66vd2mdu 84 18 as as RB cord-014597-66vd2mdu 84 19 well well RB cord-014597-66vd2mdu 84 20 as as IN cord-014597-66vd2mdu 84 21 the the DT cord-014597-66vd2mdu 84 22 matriptase matriptase JJ cord-014597-66vd2mdu 84 23 knockout knockout NN cord-014597-66vd2mdu 84 24 clone clone NN cord-014597-66vd2mdu 84 25 . . . cord-014597-66vd2mdu 85 1 Samples sample NNS cord-014597-66vd2mdu 85 2 were be VBD cord-014597-66vd2mdu 85 3 analyzed analyze VBN cord-014597-66vd2mdu 85 4 by by IN cord-014597-66vd2mdu 85 5 western western JJ cord-014597-66vd2mdu 85 6 blot blot NN cord-014597-66vd2mdu 85 7 . . . cord-014597-66vd2mdu 86 1 The the DT cord-014597-66vd2mdu 86 2 intact intact JJ cord-014597-66vd2mdu 86 3 mAb mab NN cord-014597-66vd2mdu 86 4 ( ( -LRB- cord-014597-66vd2mdu 86 5 upper upper JJ cord-014597-66vd2mdu 86 6 band band NN cord-014597-66vd2mdu 86 7 ) ) -RRB- cord-014597-66vd2mdu 86 8 and and CC cord-014597-66vd2mdu 86 9 the the DT cord-014597-66vd2mdu 86 10 clipped clip VBN cord-014597-66vd2mdu 86 11 mAb mAb NNS cord-014597-66vd2mdu 86 12 ( ( -LRB- cord-014597-66vd2mdu 86 13 lower low JJR cord-014597-66vd2mdu 86 14 band band NN cord-014597-66vd2mdu 86 15 ) ) -RRB- cord-014597-66vd2mdu 86 16 are be VBP cord-014597-66vd2mdu 86 17 indicated indicate VBN cord-014597-66vd2mdu 86 18 by by IN cord-014597-66vd2mdu 86 19 arrows arrow NNS cord-014597-66vd2mdu 86 20 . . . cord-014597-66vd2mdu 87 1 No no DT cord-014597-66vd2mdu 87 2 proteolytic proteolytic JJ cord-014597-66vd2mdu 87 3 degradation degradation NN cord-014597-66vd2mdu 87 4 could could MD cord-014597-66vd2mdu 87 5 be be VB cord-014597-66vd2mdu 87 6 detected detect VBN cord-014597-66vd2mdu 87 7 in in IN cord-014597-66vd2mdu 87 8 the the DT cord-014597-66vd2mdu 87 9 samples sample NNS cord-014597-66vd2mdu 87 10 originating originate VBG cord-014597-66vd2mdu 87 11 from from IN cord-014597-66vd2mdu 87 12 the the DT cord-014597-66vd2mdu 87 13 matriptase matriptase JJ cord-014597-66vd2mdu 87 14 KO KO NNP cord-014597-66vd2mdu 87 15 clone clone NN cord-014597-66vd2mdu 87 16 . . . cord-014597-66vd2mdu 88 1 d d NNP cord-014597-66vd2mdu 88 2 Cell Cell NNP cord-014597-66vd2mdu 88 3 growth growth NN cord-014597-66vd2mdu 88 4 , , , cord-014597-66vd2mdu 88 5 viability viability NN cord-014597-66vd2mdu 88 6 and and CC cord-014597-66vd2mdu 88 7 productivity productivity NN cord-014597-66vd2mdu 88 8 in in IN cord-014597-66vd2mdu 88 9 AMBR AMBR NNP cord-014597-66vd2mdu 88 10 ( ( -LRB- cord-014597-66vd2mdu 88 11 fed fed NNP cord-014597-66vd2mdu 88 12 batch batch NN cord-014597-66vd2mdu 88 13 with with IN cord-014597-66vd2mdu 88 14 temperature temperature NN cord-014597-66vd2mdu 88 15 shift shift NN cord-014597-66vd2mdu 88 16 ) ) -RRB- cord-014597-66vd2mdu 88 17 . . . cord-014597-66vd2mdu 89 1 Cell cell NN cord-014597-66vd2mdu 89 2 growth growth NN cord-014597-66vd2mdu 89 3 , , , cord-014597-66vd2mdu 89 4 viability viability NN cord-014597-66vd2mdu 89 5 and and CC cord-014597-66vd2mdu 89 6 volumetric volumetric JJ cord-014597-66vd2mdu 89 7 productivity productivity NN cord-014597-66vd2mdu 89 8 profiles profile NNS cord-014597-66vd2mdu 89 9 of of IN cord-014597-66vd2mdu 89 10 wt wt NNP cord-014597-66vd2mdu 89 11 CHO CHO NNP cord-014597-66vd2mdu 89 12 - - HYPH cord-014597-66vd2mdu 89 13 K1 K1 NNP cord-014597-66vd2mdu 89 14 ( ( -LRB- cord-014597-66vd2mdu 89 15 red red JJ cord-014597-66vd2mdu 89 16 circles circle NNS cord-014597-66vd2mdu 89 17 , , , cord-014597-66vd2mdu 89 18 N=2 N=2 NNP cord-014597-66vd2mdu 89 19 ) ) -RRB- cord-014597-66vd2mdu 89 20 and and CC cord-014597-66vd2mdu 89 21 matriptase matriptase NNP cord-014597-66vd2mdu 89 22 KO KO NNP cord-014597-66vd2mdu 89 23 clone clone NN cord-014597-66vd2mdu 89 24 ( ( -LRB- cord-014597-66vd2mdu 89 25 blue blue JJ cord-014597-66vd2mdu 89 26 squares square NNS cord-014597-66vd2mdu 89 27 , , , cord-014597-66vd2mdu 89 28 N=1 N=1 NNP cord-014597-66vd2mdu 89 29 ) ) -RRB- cord-014597-66vd2mdu 89 30 cultivated cultivate VBD cord-014597-66vd2mdu 89 31 in in IN cord-014597-66vd2mdu 89 32 15-mL 15-ml CD cord-014597-66vd2mdu 89 33 AMBR AMBR NNP cord-014597-66vd2mdu 89 34 . . . cord-014597-66vd2mdu 90 1 No no DT cord-014597-66vd2mdu 90 2 significant significant JJ cord-014597-66vd2mdu 90 3 differences difference NNS cord-014597-66vd2mdu 90 4 were be VBD cord-014597-66vd2mdu 90 5 seen see VBN cord-014597-66vd2mdu 90 6 between between IN cord-014597-66vd2mdu 90 7 WT WT NNP cord-014597-66vd2mdu 90 8 and and CC cord-014597-66vd2mdu 90 9 matriptase matriptase NN cord-014597-66vd2mdu 90 10 KO KO NNP cord-014597-66vd2mdu 90 11 clone clone NN cord-014597-66vd2mdu 90 12 regarding regard VBG cord-014597-66vd2mdu 90 13 cell cell NN cord-014597-66vd2mdu 90 14 growth growth NN cord-014597-66vd2mdu 90 15 and and CC cord-014597-66vd2mdu 90 16 viability viability NN cord-014597-66vd2mdu 90 17 . . . cord-014597-66vd2mdu 91 1 Comparable comparable JJ cord-014597-66vd2mdu 91 2 or or CC cord-014597-66vd2mdu 91 3 slightly slightly RB cord-014597-66vd2mdu 91 4 higher high JJR cord-014597-66vd2mdu 91 5 productivity productivity NN cord-014597-66vd2mdu 91 6 was be VBD cord-014597-66vd2mdu 91 7 detected detect VBN cord-014597-66vd2mdu 91 8 for for IN cord-014597-66vd2mdu 91 9 the the DT cord-014597-66vd2mdu 91 10 matriptase matriptase JJ cord-014597-66vd2mdu 91 11 KO KO NNP cord-014597-66vd2mdu 91 12 clone clone NN cord-014597-66vd2mdu 91 13 compared compare VBN cord-014597-66vd2mdu 91 14 to to IN cord-014597-66vd2mdu 91 15 the the DT cord-014597-66vd2mdu 91 16 WT WT NNP cord-014597-66vd2mdu 91 17 . . . cord-014597-66vd2mdu 92 1 e e LS cord-014597-66vd2mdu 92 2 Significant significant JJ cord-014597-66vd2mdu 92 3 reduced reduce VBN cord-014597-66vd2mdu 92 4 proteolytic proteolytic JJ cord-014597-66vd2mdu 92 5 clipping clip VBG cord-014597-66vd2mdu 92 6 applying apply VBG cord-014597-66vd2mdu 92 7 matriptase matriptase NNP cord-014597-66vd2mdu 92 8 KO KO NNP cord-014597-66vd2mdu 92 9 clone clone NN cord-014597-66vd2mdu 92 10 . . . cord-014597-66vd2mdu 93 1 The the DT cord-014597-66vd2mdu 93 2 model model NN cord-014597-66vd2mdu 93 3 mAb mab NN cord-014597-66vd2mdu 93 4 was be VBD cord-014597-66vd2mdu 93 5 stable stable JJ cord-014597-66vd2mdu 93 6 expressed express VBN cord-014597-66vd2mdu 93 7 in in IN cord-014597-66vd2mdu 93 8 CHO CHO NNP cord-014597-66vd2mdu 93 9 - - HYPH cord-014597-66vd2mdu 93 10 K1 K1 NNP cord-014597-66vd2mdu 93 11 ( ( -LRB- cord-014597-66vd2mdu 93 12 WT WT NNP cord-014597-66vd2mdu 93 13 ) ) -RRB- cord-014597-66vd2mdu 93 14 as as RB cord-014597-66vd2mdu 93 15 well well RB cord-014597-66vd2mdu 93 16 as as IN cord-014597-66vd2mdu 93 17 the the DT cord-014597-66vd2mdu 93 18 CHO CHO NNP cord-014597-66vd2mdu 93 19 - - HYPH cord-014597-66vd2mdu 93 20 K1 K1 NNP cord-014597-66vd2mdu 93 21 matriptase matriptase NN cord-014597-66vd2mdu 93 22 KO KO NNP cord-014597-66vd2mdu 93 23 clone clone NN cord-014597-66vd2mdu 93 24 . . . cord-014597-66vd2mdu 94 1 Samples sample NNS cord-014597-66vd2mdu 94 2 were be VBD cord-014597-66vd2mdu 94 3 analyzed analyze VBN cord-014597-66vd2mdu 94 4 by by IN cord-014597-66vd2mdu 94 5 western western JJ cord-014597-66vd2mdu 94 6 blot blot NN cord-014597-66vd2mdu 94 7 . . . cord-014597-66vd2mdu 95 1 The the DT cord-014597-66vd2mdu 95 2 intact intact JJ cord-014597-66vd2mdu 95 3 mAb mab NN cord-014597-66vd2mdu 95 4 ( ( -LRB- cord-014597-66vd2mdu 95 5 upper upper JJ cord-014597-66vd2mdu 95 6 band band NN cord-014597-66vd2mdu 95 7 ) ) -RRB- cord-014597-66vd2mdu 95 8 and and CC cord-014597-66vd2mdu 95 9 the the DT cord-014597-66vd2mdu 95 10 clipped clip VBN cord-014597-66vd2mdu 95 11 mAb mAb NNS cord-014597-66vd2mdu 95 12 ( ( -LRB- cord-014597-66vd2mdu 95 13 lower low JJR cord-014597-66vd2mdu 95 14 band band NN cord-014597-66vd2mdu 95 15 ) ) -RRB- cord-014597-66vd2mdu 95 16 are be VBP cord-014597-66vd2mdu 95 17 indicated indicate VBN cord-014597-66vd2mdu 95 18 by by IN cord-014597-66vd2mdu 95 19 arrows arrow NNS cord-014597-66vd2mdu 95 20 . . . cord-014597-66vd2mdu 96 1 Significant significant JJ cord-014597-66vd2mdu 96 2 reduced reduce VBN cord-014597-66vd2mdu 96 3 proteolytic proteolytic JJ cord-014597-66vd2mdu 96 4 degradation degradation NN cord-014597-66vd2mdu 96 5 could could MD cord-014597-66vd2mdu 96 6 be be VB cord-014597-66vd2mdu 96 7 detected detect VBN cord-014597-66vd2mdu 96 8 in in IN cord-014597-66vd2mdu 96 9 the the DT cord-014597-66vd2mdu 96 10 samples sample NNS cord-014597-66vd2mdu 96 11 originating originate VBG cord-014597-66vd2mdu 96 12 from from IN cord-014597-66vd2mdu 96 13 the the DT cord-014597-66vd2mdu 96 14 matriptase matriptase JJ cord-014597-66vd2mdu 96 15 KO KO NNP cord-014597-66vd2mdu 96 16 clone clone NN cord-014597-66vd2mdu 96 17 ( ( -LRB- cord-014597-66vd2mdu 96 18 3 3 CD cord-014597-66vd2mdu 96 19 samples sample NNS cord-014597-66vd2mdu 96 20 each each DT cord-014597-66vd2mdu 96 21 is be VBZ cord-014597-66vd2mdu 96 22 shown show VBN cord-014597-66vd2mdu 96 23 for for IN cord-014597-66vd2mdu 96 24 wt wt NN cord-014597-66vd2mdu 96 25 and and CC cord-014597-66vd2mdu 96 26 KO KO NNP cord-014597-66vd2mdu 96 27 cells cell NNS cord-014597-66vd2mdu 96 28 ) ) -RRB- cord-014597-66vd2mdu 97 1 The the DT cord-014597-66vd2mdu 97 2 glycosylation glycosylation NN cord-014597-66vd2mdu 97 3 of of IN cord-014597-66vd2mdu 97 4 therapeutic therapeutic JJ cord-014597-66vd2mdu 97 5 proteins protein NNS cord-014597-66vd2mdu 97 6 is be VBZ cord-014597-66vd2mdu 97 7 a a DT cord-014597-66vd2mdu 97 8 critical critical JJ cord-014597-66vd2mdu 97 9 quality quality NN cord-014597-66vd2mdu 97 10 attribute attribute NN cord-014597-66vd2mdu 97 11 ( ( -LRB- cord-014597-66vd2mdu 97 12 CQA CQA NNP cord-014597-66vd2mdu 97 13 ) ) -RRB- cord-014597-66vd2mdu 97 14 and and CC cord-014597-66vd2mdu 97 15 needs need VBZ cord-014597-66vd2mdu 97 16 to to TO cord-014597-66vd2mdu 97 17 be be VB cord-014597-66vd2mdu 97 18 analyzed analyze VBN cord-014597-66vd2mdu 97 19 during during IN cord-014597-66vd2mdu 97 20 cell cell NN cord-014597-66vd2mdu 97 21 line line NN cord-014597-66vd2mdu 97 22 and and CC cord-014597-66vd2mdu 97 23 bioprocess bioprocess NN cord-014597-66vd2mdu 97 24 development development NN cord-014597-66vd2mdu 97 25 . . . cord-014597-66vd2mdu 98 1 The the DT cord-014597-66vd2mdu 98 2 current current JJ cord-014597-66vd2mdu 98 3 methods method NNS cord-014597-66vd2mdu 98 4 for for IN cord-014597-66vd2mdu 98 5 analyzing analyze VBG cord-014597-66vd2mdu 98 6 glycosylation glycosylation NN cord-014597-66vd2mdu 98 7 are be VBP cord-014597-66vd2mdu 98 8 mainly mainly RB cord-014597-66vd2mdu 98 9 based base VBN cord-014597-66vd2mdu 98 10 on on IN cord-014597-66vd2mdu 98 11 the the DT cord-014597-66vd2mdu 98 12 enzymatic enzymatic JJ cord-014597-66vd2mdu 98 13 release release NN cord-014597-66vd2mdu 98 14 of of IN cord-014597-66vd2mdu 98 15 glycans glycan NNS cord-014597-66vd2mdu 98 16 . . . cord-014597-66vd2mdu 99 1 They -PRON- PRP cord-014597-66vd2mdu 99 2 are be VBP cord-014597-66vd2mdu 99 3 tedious tedious JJ cord-014597-66vd2mdu 99 4 and and CC cord-014597-66vd2mdu 99 5 offer offer VBP cord-014597-66vd2mdu 99 6 only only RB cord-014597-66vd2mdu 99 7 limited limited JJ cord-014597-66vd2mdu 99 8 throughput throughput NN cord-014597-66vd2mdu 99 9 , , , cord-014597-66vd2mdu 99 10 which which WDT cord-014597-66vd2mdu 99 11 makes make VBZ cord-014597-66vd2mdu 99 12 them -PRON- PRP cord-014597-66vd2mdu 99 13 unsuitable unsuitable JJ cord-014597-66vd2mdu 99 14 for for IN cord-014597-66vd2mdu 99 15 cell cell NN cord-014597-66vd2mdu 99 16 line line NN cord-014597-66vd2mdu 99 17 development development NN cord-014597-66vd2mdu 99 18 work work NN cord-014597-66vd2mdu 99 19 . . . cord-014597-66vd2mdu 100 1 In in IN cord-014597-66vd2mdu 100 2 this this DT cord-014597-66vd2mdu 100 3 study study NN cord-014597-66vd2mdu 100 4 we -PRON- PRP cord-014597-66vd2mdu 100 5 evaluated evaluate VBD cord-014597-66vd2mdu 100 6 a a DT cord-014597-66vd2mdu 100 7 novel novel JJ cord-014597-66vd2mdu 100 8 PAIA PAIA NNP cord-014597-66vd2mdu 100 9 assay assay NN cord-014597-66vd2mdu 100 10 for for IN cord-014597-66vd2mdu 100 11 measuring measure VBG cord-014597-66vd2mdu 100 12 intact intact JJ cord-014597-66vd2mdu 100 13 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 100 14 with with IN cord-014597-66vd2mdu 100 15 capture capture NN cord-014597-66vd2mdu 100 16 beads bead NNS cord-014597-66vd2mdu 100 17 and and CC cord-014597-66vd2mdu 100 18 fluorescence fluorescence NN cord-014597-66vd2mdu 100 19 labeled label VBN cord-014597-66vd2mdu 100 20 plant plant NN cord-014597-66vd2mdu 100 21 lectins lectin NNS cord-014597-66vd2mdu 100 22 to to TO cord-014597-66vd2mdu 100 23 analyze analyze VB cord-014597-66vd2mdu 100 24 glycans glycan NNS cord-014597-66vd2mdu 100 25 in in IN cord-014597-66vd2mdu 100 26 a a DT cord-014597-66vd2mdu 100 27 high high JJ cord-014597-66vd2mdu 100 28 throughput throughput NN cord-014597-66vd2mdu 100 29 384-well 384-well CD cord-014597-66vd2mdu 100 30 plate plate NN cord-014597-66vd2mdu 100 31 format format NN cord-014597-66vd2mdu 100 32 . . . cord-014597-66vd2mdu 101 1 Material material NN cord-014597-66vd2mdu 101 2 and and CC cord-014597-66vd2mdu 101 3 methods method NNS cord-014597-66vd2mdu 101 4 Analytes Analytes NNPS cord-014597-66vd2mdu 101 5 : : : cord-014597-66vd2mdu 101 6 Erbitux Erbitux NNP cord-014597-66vd2mdu 101 7 © © NNP cord-014597-66vd2mdu 101 8 , , , cord-014597-66vd2mdu 101 9 Mabthera Mabthera NNP cord-014597-66vd2mdu 101 10 © © NNP cord-014597-66vd2mdu 101 11 , , , cord-014597-66vd2mdu 101 12 Arzerra Arzerra NNP cord-014597-66vd2mdu 101 13 © © NNP cord-014597-66vd2mdu 102 1 and and CC cord-014597-66vd2mdu 102 2 Avastin Avastin NNP cord-014597-66vd2mdu 102 3 © © NNP cord-014597-66vd2mdu 102 4 . . . cord-014597-66vd2mdu 103 1 Two two CD cord-014597-66vd2mdu 103 2 glycoengineered glycoengineered JJ cord-014597-66vd2mdu 103 3 variants variant NNS cord-014597-66vd2mdu 103 4 of of IN cord-014597-66vd2mdu 103 5 one one CD cord-014597-66vd2mdu 103 6 IgG igg NN cord-014597-66vd2mdu 103 7 were be VBD cord-014597-66vd2mdu 103 8 kindly kindly RB cord-014597-66vd2mdu 103 9 provided provide VBN cord-014597-66vd2mdu 103 10 by by IN cord-014597-66vd2mdu 103 11 Merck Merck NNP cord-014597-66vd2mdu 103 12 ( ( -LRB- cord-014597-66vd2mdu 103 13 Vevey Vevey NNP cord-014597-66vd2mdu 103 14 , , , cord-014597-66vd2mdu 103 15 Switzerland Switzerland NNP cord-014597-66vd2mdu 103 16 ) ) -RRB- cord-014597-66vd2mdu 103 17 . . . cord-014597-66vd2mdu 104 1 All all DT cord-014597-66vd2mdu 104 2 analytes analyte NNS cord-014597-66vd2mdu 104 3 were be VBD cord-014597-66vd2mdu 104 4 spiked spike VBN cord-014597-66vd2mdu 104 5 into into IN cord-014597-66vd2mdu 104 6 CHO CHO NNP cord-014597-66vd2mdu 104 7 - - HYPH cord-014597-66vd2mdu 104 8 K1 K1 NNP cord-014597-66vd2mdu 104 9 cell cell NN cord-014597-66vd2mdu 104 10 culture culture NN cord-014597-66vd2mdu 104 11 supernatant supernatant JJ cord-014597-66vd2mdu 104 12 or or CC cord-014597-66vd2mdu 104 13 buffer buffer NN cord-014597-66vd2mdu 104 14 , , , cord-014597-66vd2mdu 104 15 diluted dilute VBN cord-014597-66vd2mdu 104 16 1:1 1:1 CD cord-014597-66vd2mdu 104 17 with with IN cord-014597-66vd2mdu 104 18 a a DT cord-014597-66vd2mdu 104 19 denaturation denaturation NN cord-014597-66vd2mdu 104 20 solution solution NN cord-014597-66vd2mdu 104 21 and and CC cord-014597-66vd2mdu 104 22 incubated incubate VBN cord-014597-66vd2mdu 104 23 at at IN cord-014597-66vd2mdu 104 24 65 65 CD cord-014597-66vd2mdu 104 25 or or CC cord-014597-66vd2mdu 104 26 70 70 CD cord-014597-66vd2mdu 104 27 ° ° NN cord-014597-66vd2mdu 104 28 C c NN cord-014597-66vd2mdu 104 29 for for IN cord-014597-66vd2mdu 104 30 20 20 CD cord-014597-66vd2mdu 104 31 minutes minute NNS cord-014597-66vd2mdu 104 32 to to TO cord-014597-66vd2mdu 104 33 expose expose VB cord-014597-66vd2mdu 104 34 the the DT cord-014597-66vd2mdu 104 35 Fc Fc NNP cord-014597-66vd2mdu 104 36 glycans glycan NNS cord-014597-66vd2mdu 104 37 . . . cord-014597-66vd2mdu 105 1 Erbitux Erbitux NNP cord-014597-66vd2mdu 105 2 samples sample NNS cord-014597-66vd2mdu 105 3 were be VBD cord-014597-66vd2mdu 105 4 analyzed analyze VBN cord-014597-66vd2mdu 105 5 under under IN cord-014597-66vd2mdu 105 6 denaturing denaturing JJ cord-014597-66vd2mdu 105 7 conditions condition NNS cord-014597-66vd2mdu 105 8 to to TO cord-014597-66vd2mdu 105 9 detect detect VB cord-014597-66vd2mdu 105 10 Fab Fab NNP cord-014597-66vd2mdu 105 11 - - : cord-014597-66vd2mdu 105 12 and and CC cord-014597-66vd2mdu 105 13 Fc Fc NNP cord-014597-66vd2mdu 105 14 - - HYPH cord-014597-66vd2mdu 105 15 glycosylation glycosylation NN cord-014597-66vd2mdu 105 16 and and CC cord-014597-66vd2mdu 105 17 in in IN cord-014597-66vd2mdu 105 18 native native JJ cord-014597-66vd2mdu 105 19 conditions condition NNS cord-014597-66vd2mdu 105 20 for for IN cord-014597-66vd2mdu 105 21 Fab fab JJ cord-014597-66vd2mdu 105 22 glycosylation glycosylation NN cord-014597-66vd2mdu 105 23 only only RB cord-014597-66vd2mdu 105 24 . . . cord-014597-66vd2mdu 106 1 10μL 10μl CD cord-014597-66vd2mdu 106 2 of of IN cord-014597-66vd2mdu 106 3 pretreated pretreate VBN cord-014597-66vd2mdu 106 4 sample sample NN cord-014597-66vd2mdu 106 5 was be VBD cord-014597-66vd2mdu 106 6 added add VBN cord-014597-66vd2mdu 106 7 to to IN cord-014597-66vd2mdu 106 8 each each DT cord-014597-66vd2mdu 106 9 well well NN cord-014597-66vd2mdu 106 10 of of IN cord-014597-66vd2mdu 106 11 the the DT cord-014597-66vd2mdu 106 12 special special JJ cord-014597-66vd2mdu 106 13 384-well 384-well CD cord-014597-66vd2mdu 106 14 PAIAplate paiaplate NN cord-014597-66vd2mdu 106 15 , , , cord-014597-66vd2mdu 106 16 containing contain VBG cord-014597-66vd2mdu 106 17 labeled label VBN cord-014597-66vd2mdu 106 18 lectin lectin NN cord-014597-66vd2mdu 106 19 and and CC cord-014597-66vd2mdu 106 20 capture capture NN cord-014597-66vd2mdu 106 21 beads bead NNS cord-014597-66vd2mdu 106 22 . . . cord-014597-66vd2mdu 107 1 The the DT cord-014597-66vd2mdu 107 2 microplate microplate NN cord-014597-66vd2mdu 107 3 was be VBD cord-014597-66vd2mdu 107 4 incubated incubate VBN cord-014597-66vd2mdu 107 5 for for IN cord-014597-66vd2mdu 107 6 45 45 CD cord-014597-66vd2mdu 107 7 minutes minute NNS cord-014597-66vd2mdu 107 8 at at IN cord-014597-66vd2mdu 107 9 1800 1800 CD cord-014597-66vd2mdu 107 10 rpm rpm NN cord-014597-66vd2mdu 107 11 on on IN cord-014597-66vd2mdu 107 12 an an DT cord-014597-66vd2mdu 107 13 orbital orbital JJ cord-014597-66vd2mdu 107 14 shaker shaker NN cord-014597-66vd2mdu 107 15 at at IN cord-014597-66vd2mdu 107 16 room room NN cord-014597-66vd2mdu 107 17 temperature temperature NN cord-014597-66vd2mdu 107 18 and and CC cord-014597-66vd2mdu 107 19 spun spin VBD cord-014597-66vd2mdu 107 20 down down RP cord-014597-66vd2mdu 107 21 at at IN cord-014597-66vd2mdu 107 22 500 500 CD cord-014597-66vd2mdu 107 23 xg xg NNS cord-014597-66vd2mdu 107 24 . . . cord-014597-66vd2mdu 108 1 The the DT cord-014597-66vd2mdu 108 2 read read NN cord-014597-66vd2mdu 108 3 - - HYPH cord-014597-66vd2mdu 108 4 out out NN cord-014597-66vd2mdu 108 5 was be VBD cord-014597-66vd2mdu 108 6 done do VBN cord-014597-66vd2mdu 108 7 on on IN cord-014597-66vd2mdu 108 8 a a DT cord-014597-66vd2mdu 108 9 fluorescence fluorescence NN cord-014597-66vd2mdu 108 10 microscope microscope NN cord-014597-66vd2mdu 108 11 ( ( -LRB- cord-014597-66vd2mdu 108 12 SynenTec SynenTec NNP cord-014597-66vd2mdu 108 13 , , , cord-014597-66vd2mdu 108 14 Elmshorn Elmshorn NNP cord-014597-66vd2mdu 108 15 , , , cord-014597-66vd2mdu 108 16 Germany Germany NNP cord-014597-66vd2mdu 108 17 ) ) -RRB- cord-014597-66vd2mdu 108 18 in in IN cord-014597-66vd2mdu 108 19 less less JJR cord-014597-66vd2mdu 108 20 than than IN cord-014597-66vd2mdu 108 21 five five CD cord-014597-66vd2mdu 108 22 minutes minute NNS cord-014597-66vd2mdu 108 23 . . . cord-014597-66vd2mdu 109 1 Results result NNS cord-014597-66vd2mdu 109 2 Figure Figure NNP cord-014597-66vd2mdu 109 3 1a 1a CD cord-014597-66vd2mdu 109 4 : : : cord-014597-66vd2mdu 110 1 Lectin Lectin NNP cord-014597-66vd2mdu 110 2 binding bind VBG cord-014597-66vd2mdu 110 3 profiles profile NNS cord-014597-66vd2mdu 110 4 of of IN cord-014597-66vd2mdu 110 5 different different JJ cord-014597-66vd2mdu 110 6 IgGs IgGs NNP cord-014597-66vd2mdu 110 7 . . . cord-014597-66vd2mdu 111 1 The the DT cord-014597-66vd2mdu 111 2 analysis analysis NN cord-014597-66vd2mdu 111 3 of of IN cord-014597-66vd2mdu 111 4 different different JJ cord-014597-66vd2mdu 111 5 IgG igg NN cord-014597-66vd2mdu 111 6 results result NNS cord-014597-66vd2mdu 111 7 in in IN cord-014597-66vd2mdu 111 8 lectin lectin NN cord-014597-66vd2mdu 111 9 binding bind VBG cord-014597-66vd2mdu 111 10 profiles profile NNS cord-014597-66vd2mdu 111 11 which which WDT cord-014597-66vd2mdu 111 12 show show VBP cord-014597-66vd2mdu 111 13 the the DT cord-014597-66vd2mdu 111 14 different different JJ cord-014597-66vd2mdu 111 15 degrees degree NNS cord-014597-66vd2mdu 111 16 in in IN cord-014597-66vd2mdu 111 17 glycosylation glycosylation NN cord-014597-66vd2mdu 111 18 . . . cord-014597-66vd2mdu 112 1 High high JJ cord-014597-66vd2mdu 112 2 abundance abundance NN cord-014597-66vd2mdu 112 3 of of IN cord-014597-66vd2mdu 112 4 sugars sugar NNS cord-014597-66vd2mdu 112 5 leads lead VBZ cord-014597-66vd2mdu 112 6 to to IN cord-014597-66vd2mdu 112 7 high high JJ cord-014597-66vd2mdu 112 8 binding binding JJ cord-014597-66vd2mdu 112 9 rates rate NNS cord-014597-66vd2mdu 112 10 of of IN cord-014597-66vd2mdu 112 11 the the DT cord-014597-66vd2mdu 112 12 lectin lectin NN cord-014597-66vd2mdu 112 13 for for IN cord-014597-66vd2mdu 112 14 the the DT cord-014597-66vd2mdu 112 15 respective respective JJ cord-014597-66vd2mdu 112 16 sugar sugar NN cord-014597-66vd2mdu 112 17 . . . cord-014597-66vd2mdu 113 1 Avastin Avastin NNP cord-014597-66vd2mdu 113 2 has have VBZ cord-014597-66vd2mdu 113 3 a a DT cord-014597-66vd2mdu 113 4 very very RB cord-014597-66vd2mdu 113 5 low low JJ cord-014597-66vd2mdu 113 6 degree degree NN cord-014597-66vd2mdu 113 7 of of IN cord-014597-66vd2mdu 113 8 galactosylation galactosylation NN cord-014597-66vd2mdu 113 9 and and CC cord-014597-66vd2mdu 113 10 high high JJ cord-014597-66vd2mdu 113 11 mannose mannose NN cord-014597-66vd2mdu 113 12 species specie NNS cord-014597-66vd2mdu 113 13 compared compare VBN cord-014597-66vd2mdu 113 14 to to IN cord-014597-66vd2mdu 113 15 Mabthera Mabthera NNP cord-014597-66vd2mdu 113 16 and and CC cord-014597-66vd2mdu 113 17 Arzerra Arzerra NNP cord-014597-66vd2mdu 113 18 ( ( -LRB- cord-014597-66vd2mdu 113 19 Fig Fig NNP cord-014597-66vd2mdu 113 20 . . . cord-014597-66vd2mdu 113 21 1a 1a CD cord-014597-66vd2mdu 113 22 ) ) -RRB- cord-014597-66vd2mdu 113 23 . . . cord-014597-66vd2mdu 114 1 Only only RB cord-014597-66vd2mdu 114 2 Arzerra Arzerra NNP cord-014597-66vd2mdu 114 3 is be VBZ cord-014597-66vd2mdu 114 4 carrying carry VBG cord-014597-66vd2mdu 114 5 glycans glycan NNS cord-014597-66vd2mdu 114 6 with with IN cord-014597-66vd2mdu 114 7 2 2 CD cord-014597-66vd2mdu 114 8 - - SYM cord-014597-66vd2mdu 114 9 6 6 CD cord-014597-66vd2mdu 114 10 linked link VBN cord-014597-66vd2mdu 114 11 sialic sialic NN cord-014597-66vd2mdu 114 12 acids acid NNS cord-014597-66vd2mdu 114 13 . . . cord-014597-66vd2mdu 115 1 These these DT cord-014597-66vd2mdu 115 2 findings finding NNS cord-014597-66vd2mdu 115 3 are be VBP cord-014597-66vd2mdu 115 4 in in IN cord-014597-66vd2mdu 115 5 line line NN cord-014597-66vd2mdu 115 6 with with IN cord-014597-66vd2mdu 115 7 results result NNS cord-014597-66vd2mdu 115 8 from from IN cord-014597-66vd2mdu 115 9 literature literature NN cord-014597-66vd2mdu 115 10 [ [ -LRB- cord-014597-66vd2mdu 115 11 1 1 CD cord-014597-66vd2mdu 115 12 ] ] -RRB- cord-014597-66vd2mdu 115 13 . . . cord-014597-66vd2mdu 116 1 Figure figure NN cord-014597-66vd2mdu 116 2 1b 1b CD cord-014597-66vd2mdu 116 3 : : : cord-014597-66vd2mdu 116 4 Distinction distinction NN cord-014597-66vd2mdu 116 5 between between IN cord-014597-66vd2mdu 116 6 Fc Fc NNP cord-014597-66vd2mdu 116 7 and and CC cord-014597-66vd2mdu 116 8 Fab fab JJ cord-014597-66vd2mdu 116 9 glycosylation glycosylation NN cord-014597-66vd2mdu 116 10 in in IN cord-014597-66vd2mdu 116 11 Erbitux Erbitux NNP cord-014597-66vd2mdu 116 12 . . . cord-014597-66vd2mdu 117 1 Without without IN cord-014597-66vd2mdu 117 2 denaturation denaturation NN cord-014597-66vd2mdu 117 3 only only RB cord-014597-66vd2mdu 117 4 the the DT cord-014597-66vd2mdu 117 5 Fab fab JJ cord-014597-66vd2mdu 117 6 glycans glycan NNS cord-014597-66vd2mdu 117 7 are be VBP cord-014597-66vd2mdu 117 8 detectable detectable JJ cord-014597-66vd2mdu 117 9 in in IN cord-014597-66vd2mdu 117 10 Erbitux Erbitux NNP cord-014597-66vd2mdu 117 11 . . . cord-014597-66vd2mdu 118 1 Denaturation Denaturation NNP cord-014597-66vd2mdu 118 2 leads lead VBZ cord-014597-66vd2mdu 118 3 to to IN cord-014597-66vd2mdu 118 4 additional additional JJ cord-014597-66vd2mdu 118 5 exposure exposure NN cord-014597-66vd2mdu 118 6 of of IN cord-014597-66vd2mdu 118 7 the the DT cord-014597-66vd2mdu 118 8 Fc Fc NNP cord-014597-66vd2mdu 118 9 glycans glycan NNS cord-014597-66vd2mdu 118 10 and and CC cord-014597-66vd2mdu 118 11 thus thus RB cord-014597-66vd2mdu 118 12 higher high JJR cord-014597-66vd2mdu 118 13 lectin lectin NN cord-014597-66vd2mdu 118 14 binding bind VBG cord-014597-66vd2mdu 118 15 rates rate NNS cord-014597-66vd2mdu 118 16 compared compare VBN cord-014597-66vd2mdu 118 17 to to IN cord-014597-66vd2mdu 118 18 native native JJ cord-014597-66vd2mdu 118 19 Erbitux Erbitux NNP cord-014597-66vd2mdu 118 20 . . . cord-014597-66vd2mdu 119 1 GNA GNA NNP cord-014597-66vd2mdu 119 2 and and CC cord-014597-66vd2mdu 119 3 NPL NPL NNP cord-014597-66vd2mdu 119 4 only only RB cord-014597-66vd2mdu 119 5 bind bind VBP cord-014597-66vd2mdu 119 6 to to IN cord-014597-66vd2mdu 119 7 denatured denatured JJ cord-014597-66vd2mdu 119 8 Erbitux Erbitux NNP cord-014597-66vd2mdu 119 9 indicating indicate VBG cord-014597-66vd2mdu 119 10 that that IN cord-014597-66vd2mdu 119 11 the the DT cord-014597-66vd2mdu 119 12 high high JJ cord-014597-66vd2mdu 119 13 mannose mannose NN cord-014597-66vd2mdu 119 14 glycans glycan NNS cord-014597-66vd2mdu 119 15 are be VBP cord-014597-66vd2mdu 119 16 only only RB cord-014597-66vd2mdu 119 17 present present JJ cord-014597-66vd2mdu 119 18 on on IN cord-014597-66vd2mdu 119 19 the the DT cord-014597-66vd2mdu 119 20 Fc Fc NNP cord-014597-66vd2mdu 119 21 part part NN cord-014597-66vd2mdu 119 22 . . . cord-014597-66vd2mdu 120 1 The the DT cord-014597-66vd2mdu 120 2 equal equal JJ cord-014597-66vd2mdu 120 3 SNA SNA NNP cord-014597-66vd2mdu 120 4 binding binding NN cord-014597-66vd2mdu 120 5 rates rate NNS cord-014597-66vd2mdu 120 6 for for IN cord-014597-66vd2mdu 120 7 both both DT cord-014597-66vd2mdu 120 8 conditions condition NNS cord-014597-66vd2mdu 120 9 confirm confirm VBP cord-014597-66vd2mdu 120 10 that that IN cord-014597-66vd2mdu 120 11 the the DT cord-014597-66vd2mdu 120 12 2 2 CD cord-014597-66vd2mdu 120 13 - - SYM cord-014597-66vd2mdu 120 14 6 6 CD cord-014597-66vd2mdu 120 15 linked link VBN cord-014597-66vd2mdu 120 16 sialic sialic JJ cord-014597-66vd2mdu 120 17 acids acid NNS cord-014597-66vd2mdu 120 18 are be VBP cord-014597-66vd2mdu 120 19 almost almost RB cord-014597-66vd2mdu 120 20 exclusively exclusively RB cord-014597-66vd2mdu 120 21 found find VBN cord-014597-66vd2mdu 120 22 on on IN cord-014597-66vd2mdu 120 23 the the DT cord-014597-66vd2mdu 120 24 Fab fab JJ cord-014597-66vd2mdu 120 25 part part NN cord-014597-66vd2mdu 120 26 . . . cord-014597-66vd2mdu 121 1 This this DT cord-014597-66vd2mdu 121 2 is be VBZ cord-014597-66vd2mdu 121 3 in in IN cord-014597-66vd2mdu 121 4 agreement agreement NN cord-014597-66vd2mdu 121 5 with with IN cord-014597-66vd2mdu 121 6 published publish VBN cord-014597-66vd2mdu 121 7 data datum NNS cord-014597-66vd2mdu 121 8 [ [ -LRB- cord-014597-66vd2mdu 121 9 2 2 CD cord-014597-66vd2mdu 121 10 ] ] -RRB- cord-014597-66vd2mdu 121 11 . . . cord-014597-66vd2mdu 122 1 Figure figure NN cord-014597-66vd2mdu 122 2 1c 1c CD cord-014597-66vd2mdu 122 3 : : : cord-014597-66vd2mdu 123 1 Lectin Lectin NNP cord-014597-66vd2mdu 123 2 binding bind VBG cord-014597-66vd2mdu 123 3 rates rate NNS cord-014597-66vd2mdu 123 4 correlate correlate VBP cord-014597-66vd2mdu 123 5 with with IN cord-014597-66vd2mdu 123 6 the the DT cord-014597-66vd2mdu 123 7 levels level NNS cord-014597-66vd2mdu 123 8 of of IN cord-014597-66vd2mdu 123 9 galactosylation galactosylation NN cord-014597-66vd2mdu 123 10 and and CC cord-014597-66vd2mdu 123 11 fucosylation fucosylation NN cord-014597-66vd2mdu 123 12 . . . cord-014597-66vd2mdu 124 1 Increasing increase VBG cord-014597-66vd2mdu 124 2 degrees degree NNS cord-014597-66vd2mdu 124 3 of of IN cord-014597-66vd2mdu 124 4 glycosylation glycosylation NN cord-014597-66vd2mdu 124 5 in in IN cord-014597-66vd2mdu 124 6 the the DT cord-014597-66vd2mdu 124 7 mixtures mixture NNS cord-014597-66vd2mdu 124 8 of of IN cord-014597-66vd2mdu 124 9 the the DT cord-014597-66vd2mdu 124 10 glycan glycan NN cord-014597-66vd2mdu 124 11 variants variant NNS cord-014597-66vd2mdu 124 12 from from IN cord-014597-66vd2mdu 124 13 Merck Merck NNP cord-014597-66vd2mdu 124 14 lead lead VBP cord-014597-66vd2mdu 124 15 to to IN cord-014597-66vd2mdu 124 16 higher high JJR cord-014597-66vd2mdu 124 17 lectin lectin NN cord-014597-66vd2mdu 124 18 binding bind VBG cord-014597-66vd2mdu 124 19 rates rate NNS cord-014597-66vd2mdu 124 20 for for IN cord-014597-66vd2mdu 124 21 all all DT cord-014597-66vd2mdu 124 22 galactose galactose NN cord-014597-66vd2mdu 124 23 and and CC cord-014597-66vd2mdu 124 24 fucose fucose JJ cord-014597-66vd2mdu 124 25 markers marker NNS cord-014597-66vd2mdu 124 26 proving prove VBG cord-014597-66vd2mdu 124 27 that that IN cord-014597-66vd2mdu 124 28 quantitative quantitative JJ cord-014597-66vd2mdu 124 29 analysis analysis NN cord-014597-66vd2mdu 124 30 can can MD cord-014597-66vd2mdu 124 31 be be VB cord-014597-66vd2mdu 124 32 performed perform VBN cord-014597-66vd2mdu 124 33 with with IN cord-014597-66vd2mdu 124 34 these these DT cord-014597-66vd2mdu 124 35 assays assay NNS cord-014597-66vd2mdu 124 36 . . . cord-014597-66vd2mdu 125 1 The the DT cord-014597-66vd2mdu 125 2 ConA ConA NNP cord-014597-66vd2mdu 125 3 lectin lectin NN cord-014597-66vd2mdu 125 4 which which WDT cord-014597-66vd2mdu 125 5 binds bind VBZ cord-014597-66vd2mdu 125 6 to to IN cord-014597-66vd2mdu 125 7 the the DT cord-014597-66vd2mdu 125 8 common common JJ cord-014597-66vd2mdu 125 9 core core NN cord-014597-66vd2mdu 125 10 mannose mannose NN cord-014597-66vd2mdu 125 11 glycan glycan NN cord-014597-66vd2mdu 125 12 motive motive NN cord-014597-66vd2mdu 125 13 remains remain VBZ cord-014597-66vd2mdu 125 14 at at IN cord-014597-66vd2mdu 125 15 the the DT cord-014597-66vd2mdu 125 16 same same JJ cord-014597-66vd2mdu 125 17 level level NN cord-014597-66vd2mdu 125 18 , , , cord-014597-66vd2mdu 125 19 suggesting suggest VBG cord-014597-66vd2mdu 125 20 that that IN cord-014597-66vd2mdu 125 21 the the DT cord-014597-66vd2mdu 125 22 Fc Fc NNP cord-014597-66vd2mdu 125 23 glycans glycan NNS cord-014597-66vd2mdu 125 24 were be VBD cord-014597-66vd2mdu 125 25 similarly similarly RB cord-014597-66vd2mdu 125 26 exposed expose VBN cord-014597-66vd2mdu 125 27 in in IN cord-014597-66vd2mdu 125 28 all all DT cord-014597-66vd2mdu 125 29 samples sample NNS cord-014597-66vd2mdu 125 30 . . . cord-014597-66vd2mdu 126 1 The the DT cord-014597-66vd2mdu 126 2 results result NNS cord-014597-66vd2mdu 126 3 demonstrate demonstrate VBP cord-014597-66vd2mdu 126 4 that that IN cord-014597-66vd2mdu 126 5 PAIA PAIA NNP cord-014597-66vd2mdu 126 6 assays assay NNS cord-014597-66vd2mdu 126 7 are be VBP cord-014597-66vd2mdu 126 8 capable capable JJ cord-014597-66vd2mdu 126 9 of of IN cord-014597-66vd2mdu 126 10 quickly quickly RB cord-014597-66vd2mdu 126 11 detecting detect VBG cord-014597-66vd2mdu 126 12 differences difference NNS cord-014597-66vd2mdu 126 13 in in IN cord-014597-66vd2mdu 126 14 glycan glycan NN cord-014597-66vd2mdu 126 15 patterns pattern NNS cord-014597-66vd2mdu 126 16 of of IN cord-014597-66vd2mdu 126 17 different different JJ cord-014597-66vd2mdu 126 18 antibodies antibody NNS cord-014597-66vd2mdu 126 19 . . . cord-014597-66vd2mdu 127 1 In in IN cord-014597-66vd2mdu 127 2 addition addition NN cord-014597-66vd2mdu 127 3 it -PRON- PRP cord-014597-66vd2mdu 127 4 was be VBD cord-014597-66vd2mdu 127 5 shown show VBN cord-014597-66vd2mdu 127 6 that that IN cord-014597-66vd2mdu 127 7 glycan glycan NN cord-014597-66vd2mdu 127 8 variants variant NNS cord-014597-66vd2mdu 127 9 of of IN cord-014597-66vd2mdu 127 10 the the DT cord-014597-66vd2mdu 127 11 same same JJ cord-014597-66vd2mdu 127 12 IgG igg NN cord-014597-66vd2mdu 127 13 can can MD cord-014597-66vd2mdu 127 14 be be VB cord-014597-66vd2mdu 127 15 analyzed analyze VBN cord-014597-66vd2mdu 127 16 quantitatively quantitatively RB cord-014597-66vd2mdu 127 17 . . . cord-014597-66vd2mdu 128 1 And and CC cord-014597-66vd2mdu 128 2 finally finally RB cord-014597-66vd2mdu 128 3 we -PRON- PRP cord-014597-66vd2mdu 128 4 could could MD cord-014597-66vd2mdu 128 5 confirm confirm VB cord-014597-66vd2mdu 128 6 the the DT cord-014597-66vd2mdu 128 7 differences difference NNS cord-014597-66vd2mdu 128 8 in in IN cord-014597-66vd2mdu 128 9 Fab Fab NNP cord-014597-66vd2mdu 128 10 and and CC cord-014597-66vd2mdu 128 11 Fc Fc NNP cord-014597-66vd2mdu 128 12 glycosylation glycosylation NN cord-014597-66vd2mdu 128 13 in in IN cord-014597-66vd2mdu 128 14 Erbitux Erbitux NNP cord-014597-66vd2mdu 128 15 . . . cord-014597-66vd2mdu 129 1 We -PRON- PRP cord-014597-66vd2mdu 129 2 believe believe VBP cord-014597-66vd2mdu 129 3 that that IN cord-014597-66vd2mdu 129 4 bead bead NN cord-014597-66vd2mdu 129 5 - - HYPH cord-014597-66vd2mdu 129 6 based base VBN cord-014597-66vd2mdu 129 7 assays assay NNS cord-014597-66vd2mdu 129 8 with with IN cord-014597-66vd2mdu 129 9 lectins lectin NNS cord-014597-66vd2mdu 129 10 have have VBP cord-014597-66vd2mdu 129 11 a a DT cord-014597-66vd2mdu 129 12 great great JJ cord-014597-66vd2mdu 129 13 potential potential NN cord-014597-66vd2mdu 129 14 for for IN cord-014597-66vd2mdu 129 15 monitoring monitor VBG cord-014597-66vd2mdu 129 16 product product NN cord-014597-66vd2mdu 129 17 quality quality NN cord-014597-66vd2mdu 129 18 early early RB cord-014597-66vd2mdu 129 19 in in IN cord-014597-66vd2mdu 129 20 the the DT cord-014597-66vd2mdu 129 21 development development NN cord-014597-66vd2mdu 129 22 process process NN cord-014597-66vd2mdu 129 23 . . . cord-014597-66vd2mdu 130 1 Background Background NNP cord-014597-66vd2mdu 130 2 Gene Gene NNP cord-014597-66vd2mdu 130 3 - - HYPH cord-014597-66vd2mdu 130 4 and and CC cord-014597-66vd2mdu 130 5 cell cell NN cord-014597-66vd2mdu 130 6 therapy therapy NN cord-014597-66vd2mdu 130 7 - - HYPH cord-014597-66vd2mdu 130 8 based base VBN cord-014597-66vd2mdu 130 9 medicines medicine NNS cord-014597-66vd2mdu 130 10 are be VBP cord-014597-66vd2mdu 130 11 experiencing experience VBG cord-014597-66vd2mdu 130 12 resurgence resurgence NN cord-014597-66vd2mdu 130 13 due due IN cord-014597-66vd2mdu 130 14 to to IN cord-014597-66vd2mdu 130 15 the the DT cord-014597-66vd2mdu 130 16 introduction introduction NN cord-014597-66vd2mdu 130 17 of of IN cord-014597-66vd2mdu 130 18 " " `` cord-014597-66vd2mdu 130 19 next next JJ cord-014597-66vd2mdu 130 20 generation generation NN cord-014597-66vd2mdu 130 21 " " '' cord-014597-66vd2mdu 130 22 transfer transfer NN cord-014597-66vd2mdu 130 23 viral viral JJ cord-014597-66vd2mdu 130 24 vectors vector NNS cord-014597-66vd2mdu 130 25 , , , cord-014597-66vd2mdu 130 26 which which WDT cord-014597-66vd2mdu 130 27 have have VBP cord-014597-66vd2mdu 130 28 demonstrated demonstrate VBN cord-014597-66vd2mdu 130 29 improved improved JJ cord-014597-66vd2mdu 130 30 safety safety NN cord-014597-66vd2mdu 130 31 and and CC cord-014597-66vd2mdu 130 32 efficacy efficacy NN cord-014597-66vd2mdu 130 33 . . . cord-014597-66vd2mdu 131 1 Adeno Adeno NNP cord-014597-66vd2mdu 131 2 associated associate VBD cord-014597-66vd2mdu 131 3 viruses virus NNS cord-014597-66vd2mdu 131 4 ( ( -LRB- cord-014597-66vd2mdu 131 5 AAV AAV NNP cord-014597-66vd2mdu 131 6 ) ) -RRB- cord-014597-66vd2mdu 131 7 and and CC cord-014597-66vd2mdu 132 1 lentiviruses lentiviruse NNS cord-014597-66vd2mdu 132 2 are be VBP cord-014597-66vd2mdu 132 3 very very RB cord-014597-66vd2mdu 132 4 commonly commonly RB cord-014597-66vd2mdu 132 5 used use VBN cord-014597-66vd2mdu 132 6 in in IN cord-014597-66vd2mdu 132 7 therapeutics therapeutic NNS cord-014597-66vd2mdu 132 8 and and CC cord-014597-66vd2mdu 132 9 often often RB cord-014597-66vd2mdu 132 10 produced produce VBN cord-014597-66vd2mdu 132 11 by by IN cord-014597-66vd2mdu 132 12 transient transient JJ cord-014597-66vd2mdu 132 13 gene gene NN cord-014597-66vd2mdu 132 14 expression expression NN cord-014597-66vd2mdu 132 15 , , , cord-014597-66vd2mdu 132 16 using use VBG cord-014597-66vd2mdu 132 17 PEI PEI NNP cord-014597-66vd2mdu 132 18 - - HYPH cord-014597-66vd2mdu 132 19 mediated mediate VBN cord-014597-66vd2mdu 132 20 transient transient JJ cord-014597-66vd2mdu 132 21 transfection transfection NN cord-014597-66vd2mdu 132 22 in in IN cord-014597-66vd2mdu 132 23 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 132 24 or or CC cord-014597-66vd2mdu 132 25 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 132 26 T t NN cord-014597-66vd2mdu 132 27 cells cell NNS cord-014597-66vd2mdu 132 28 [ [ -LRB- cord-014597-66vd2mdu 132 29 1 1 CD cord-014597-66vd2mdu 132 30 ] ] -RRB- cord-014597-66vd2mdu 132 31 . . . cord-014597-66vd2mdu 133 1 The the DT cord-014597-66vd2mdu 133 2 critical critical JJ cord-014597-66vd2mdu 133 3 raw raw JJ cord-014597-66vd2mdu 133 4 materials material NNS cord-014597-66vd2mdu 133 5 needed need VBN cord-014597-66vd2mdu 133 6 for for IN cord-014597-66vd2mdu 133 7 cGMP cGMP NNP cord-014597-66vd2mdu 133 8 vector vector NN cord-014597-66vd2mdu 133 9 production production NN cord-014597-66vd2mdu 133 10 must must MD cord-014597-66vd2mdu 133 11 be be VB cord-014597-66vd2mdu 133 12 sourced source VBN cord-014597-66vd2mdu 133 13 from from IN cord-014597-66vd2mdu 133 14 approved approve VBN cord-014597-66vd2mdu 133 15 suppliers supplier NNS cord-014597-66vd2mdu 133 16 and and CC cord-014597-66vd2mdu 133 17 should should MD cord-014597-66vd2mdu 133 18 have have VB cord-014597-66vd2mdu 133 19 gone go VBN cord-014597-66vd2mdu 133 20 through through IN cord-014597-66vd2mdu 133 21 a a DT cord-014597-66vd2mdu 133 22 rigorous rigorous JJ cord-014597-66vd2mdu 133 23 testing testing NN cord-014597-66vd2mdu 133 24 program program NN cord-014597-66vd2mdu 133 25 to to TO cord-014597-66vd2mdu 133 26 reduce reduce VB cord-014597-66vd2mdu 133 27 the the DT cord-014597-66vd2mdu 133 28 risk risk NN cord-014597-66vd2mdu 133 29 of of IN cord-014597-66vd2mdu 133 30 introducing introduce VBG cord-014597-66vd2mdu 133 31 adventitious adventitious JJ cord-014597-66vd2mdu 133 32 agents agent NNS cord-014597-66vd2mdu 133 33 into into IN cord-014597-66vd2mdu 133 34 the the DT cord-014597-66vd2mdu 133 35 production production NN cord-014597-66vd2mdu 133 36 process process NN cord-014597-66vd2mdu 133 37 . . . cord-014597-66vd2mdu 134 1 Correspondingly correspondingly RB cord-014597-66vd2mdu 134 2 , , , cord-014597-66vd2mdu 134 3 the the DT cord-014597-66vd2mdu 134 4 PEI PEI NNP cord-014597-66vd2mdu 134 5 transfection transfection NN cord-014597-66vd2mdu 134 6 reagent reagent NN cord-014597-66vd2mdu 134 7 must must MD cord-014597-66vd2mdu 134 8 also also RB cord-014597-66vd2mdu 134 9 be be VB cord-014597-66vd2mdu 134 10 sourced source VBN cord-014597-66vd2mdu 134 11 from from IN cord-014597-66vd2mdu 134 12 a a DT cord-014597-66vd2mdu 134 13 qualified qualified JJ cord-014597-66vd2mdu 134 14 supplier supplier NN cord-014597-66vd2mdu 134 15 , , , cord-014597-66vd2mdu 134 16 and and CC cord-014597-66vd2mdu 134 17 have have VBP cord-014597-66vd2mdu 134 18 gone go VBN cord-014597-66vd2mdu 134 19 through through IN cord-014597-66vd2mdu 134 20 rigorous rigorous JJ cord-014597-66vd2mdu 134 21 testing testing NN cord-014597-66vd2mdu 134 22 to to TO cord-014597-66vd2mdu 134 23 ensure ensure VB cord-014597-66vd2mdu 134 24 reliable reliable JJ cord-014597-66vd2mdu 134 25 transfection transfection NN cord-014597-66vd2mdu 134 26 efficiencies efficiency NNS cord-014597-66vd2mdu 134 27 , , , cord-014597-66vd2mdu 134 28 and and CC cord-014597-66vd2mdu 134 29 hence hence RB cord-014597-66vd2mdu 134 30 reproducible reproducible JJ cord-014597-66vd2mdu 134 31 virus virus NN cord-014597-66vd2mdu 134 32 production production NN cord-014597-66vd2mdu 134 33 yields yield NNS cord-014597-66vd2mdu 134 34 . . . cord-014597-66vd2mdu 135 1 Here here RB cord-014597-66vd2mdu 135 2 , , , cord-014597-66vd2mdu 135 3 we -PRON- PRP cord-014597-66vd2mdu 135 4 present present VBP cord-014597-66vd2mdu 136 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 136 2 ® ® NN cord-014597-66vd2mdu 136 3 and and CC cord-014597-66vd2mdu 137 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 137 2 ® ® NNPS cord-014597-66vd2mdu 137 3 -HQ -hq NN cord-014597-66vd2mdu 137 4 , , , cord-014597-66vd2mdu 137 5 the the DT cord-014597-66vd2mdu 137 6 unique unique JJ cord-014597-66vd2mdu 137 7 PEI PEI NNP cord-014597-66vd2mdu 137 8 - - HYPH cord-014597-66vd2mdu 137 9 based base VBN cord-014597-66vd2mdu 137 10 transfection transfection NN cord-014597-66vd2mdu 137 11 reagents reagent NNS cord-014597-66vd2mdu 137 12 suitable suitable JJ cord-014597-66vd2mdu 137 13 for for IN cord-014597-66vd2mdu 137 14 use use NN cord-014597-66vd2mdu 137 15 in in IN cord-014597-66vd2mdu 137 16 process process NN cord-014597-66vd2mdu 137 17 development development NN cord-014597-66vd2mdu 137 18 and and CC cord-014597-66vd2mdu 137 19 in in IN cord-014597-66vd2mdu 137 20 cGMP cGMP NNP cord-014597-66vd2mdu 137 21 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 137 22 , , , cord-014597-66vd2mdu 137 23 respectively respectively RB cord-014597-66vd2mdu 137 24 . . . cord-014597-66vd2mdu 138 1 Unlike unlike IN cord-014597-66vd2mdu 138 2 commercially commercially RB cord-014597-66vd2mdu 138 3 available available JJ cord-014597-66vd2mdu 138 4 PEIs pei NNS cord-014597-66vd2mdu 138 5 , , , cord-014597-66vd2mdu 138 6 PEIpro PEIpro NNP cord-014597-66vd2mdu 139 1 ® ® VB cord-014597-66vd2mdu 139 2 benefits benefit NNS cord-014597-66vd2mdu 139 3 from from IN cord-014597-66vd2mdu 139 4 extensive extensive JJ cord-014597-66vd2mdu 139 5 research research NN cord-014597-66vd2mdu 139 6 and and CC cord-014597-66vd2mdu 139 7 development development NN cord-014597-66vd2mdu 139 8 in in IN cord-014597-66vd2mdu 139 9 polymer polymer NN cord-014597-66vd2mdu 139 10 chemistry chemistry NN cord-014597-66vd2mdu 139 11 and and CC cord-014597-66vd2mdu 139 12 formulation formulation NN cord-014597-66vd2mdu 139 13 for for IN cord-014597-66vd2mdu 139 14 mammalian mammalian JJ cord-014597-66vd2mdu 139 15 cell cell NN cord-014597-66vd2mdu 139 16 transfection transfection NN cord-014597-66vd2mdu 139 17 . . . cord-014597-66vd2mdu 140 1 We -PRON- PRP cord-014597-66vd2mdu 140 2 further further RB cord-014597-66vd2mdu 140 3 demonstrate demonstrate VBP cord-014597-66vd2mdu 140 4 that that IN cord-014597-66vd2mdu 140 5 PEIpro PEIpro NNP cord-014597-66vd2mdu 140 6 ® ® NN cord-014597-66vd2mdu 140 7 and and CC cord-014597-66vd2mdu 141 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 141 2 ® ® NNPS cord-014597-66vd2mdu 141 3 -HQ -hq CC cord-014597-66vd2mdu 141 4 are be VBP cord-014597-66vd2mdu 141 5 the the DT cord-014597-66vd2mdu 141 6 reagents reagent NNS cord-014597-66vd2mdu 141 7 of of IN cord-014597-66vd2mdu 141 8 choice choice NN cord-014597-66vd2mdu 141 9 for for IN cord-014597-66vd2mdu 141 10 virus virus NN cord-014597-66vd2mdu 141 11 production production NN cord-014597-66vd2mdu 141 12 runs run VBZ cord-014597-66vd2mdu 141 13 in in IN cord-014597-66vd2mdu 141 14 most most JJS cord-014597-66vd2mdu 141 15 cell cell NN cord-014597-66vd2mdu 141 16 culture culture NN cord-014597-66vd2mdu 141 17 systems system NNS cord-014597-66vd2mdu 141 18 , , , cord-014597-66vd2mdu 141 19 hence hence RB cord-014597-66vd2mdu 141 20 facilitating facilitate VBG cord-014597-66vd2mdu 141 21 the the DT cord-014597-66vd2mdu 141 22 transition transition NN cord-014597-66vd2mdu 141 23 from from IN cord-014597-66vd2mdu 141 24 initial initial JJ cord-014597-66vd2mdu 141 25 optimization optimization NN cord-014597-66vd2mdu 141 26 during during IN cord-014597-66vd2mdu 141 27 process process NN cord-014597-66vd2mdu 141 28 development development NN cord-014597-66vd2mdu 141 29 up up IN cord-014597-66vd2mdu 141 30 to to IN cord-014597-66vd2mdu 141 31 large large JJ cord-014597-66vd2mdu 141 32 - - HYPH cord-014597-66vd2mdu 141 33 scale scale NN cord-014597-66vd2mdu 141 34 therapeutic therapeutic JJ cord-014597-66vd2mdu 141 35 viral viral JJ cord-014597-66vd2mdu 141 36 vector vector NN cord-014597-66vd2mdu 141 37 production production NN cord-014597-66vd2mdu 141 38 in in IN cord-014597-66vd2mdu 141 39 adherent adherent NN cord-014597-66vd2mdu 141 40 or or CC cord-014597-66vd2mdu 141 41 suspension suspension NN cord-014597-66vd2mdu 141 42 cells cell NNS cord-014597-66vd2mdu 141 43 . . . cord-014597-66vd2mdu 142 1 Manufacturing manufacturing NN cord-014597-66vd2mdu 142 2 process process NN cord-014597-66vd2mdu 142 3 of of IN cord-014597-66vd2mdu 143 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 143 2 ® ® NN cord-014597-66vd2mdu 143 3 and and CC cord-014597-66vd2mdu 144 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 144 2 ® ® NNPS cord-014597-66vd2mdu 144 3 -HQ -hq NN cord-014597-66vd2mdu 144 4 reagents reagent NNS cord-014597-66vd2mdu 144 5 . . . cord-014597-66vd2mdu 145 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 146 1 ® ® VB cord-014597-66vd2mdu 146 2 and and CC cord-014597-66vd2mdu 147 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 147 2 ® ® NNPS cord-014597-66vd2mdu 147 3 -HQ -hq CC cord-014597-66vd2mdu 147 4 are be VBP cord-014597-66vd2mdu 147 5 fully fully RB cord-014597-66vd2mdu 147 6 synthetic synthetic JJ cord-014597-66vd2mdu 147 7 reagents reagent NNS cord-014597-66vd2mdu 147 8 , , , cord-014597-66vd2mdu 147 9 free free JJ cord-014597-66vd2mdu 147 10 of of IN cord-014597-66vd2mdu 147 11 any any DT cord-014597-66vd2mdu 147 12 animal animal NN cord-014597-66vd2mdu 147 13 - - HYPH cord-014597-66vd2mdu 147 14 origin origin NN cord-014597-66vd2mdu 147 15 components component NNS cord-014597-66vd2mdu 147 16 . . . cord-014597-66vd2mdu 148 1 In in IN cord-014597-66vd2mdu 148 2 comparison comparison NN cord-014597-66vd2mdu 148 3 to to IN cord-014597-66vd2mdu 148 4 PEIpro PEIpro NNP cord-014597-66vd2mdu 148 5 ® ® NNP cord-014597-66vd2mdu 148 6 , , , cord-014597-66vd2mdu 148 7 a a DT cord-014597-66vd2mdu 148 8 more more RBR cord-014597-66vd2mdu 148 9 extensive extensive JJ cord-014597-66vd2mdu 148 10 number number NN cord-014597-66vd2mdu 148 11 of of IN cord-014597-66vd2mdu 148 12 Quality Quality NNP cord-014597-66vd2mdu 148 13 Controls Controls NNPS cord-014597-66vd2mdu 148 14 are be VBP cord-014597-66vd2mdu 148 15 performed perform VBN cord-014597-66vd2mdu 148 16 on on IN cord-014597-66vd2mdu 148 17 PEIpro PEIpro NNP cord-014597-66vd2mdu 148 18 ® ® NNPS cord-014597-66vd2mdu 148 19 -HQ -hq NN cord-014597-66vd2mdu 148 20 to to TO cord-014597-66vd2mdu 148 21 enable enable VB cord-014597-66vd2mdu 148 22 its -PRON- PRP$ cord-014597-66vd2mdu 148 23 use use NN cord-014597-66vd2mdu 148 24 as as IN cord-014597-66vd2mdu 148 25 a a DT cord-014597-66vd2mdu 148 26 qualified qualified JJ cord-014597-66vd2mdu 148 27 raw raw JJ cord-014597-66vd2mdu 148 28 material material NN cord-014597-66vd2mdu 148 29 in in IN cord-014597-66vd2mdu 148 30 GMP GMP NNP cord-014597-66vd2mdu 148 31 processes process NNS cord-014597-66vd2mdu 148 32 for for IN cord-014597-66vd2mdu 148 33 the the DT cord-014597-66vd2mdu 148 34 manufacturing manufacturing NN cord-014597-66vd2mdu 148 35 of of IN cord-014597-66vd2mdu 148 36 clinical clinical JJ cord-014597-66vd2mdu 148 37 batches batch NNS cord-014597-66vd2mdu 148 38 of of IN cord-014597-66vd2mdu 148 39 therapeutic therapeutic JJ cord-014597-66vd2mdu 148 40 products product NNS cord-014597-66vd2mdu 148 41 . . . cord-014597-66vd2mdu 149 1 Lentivirus Lentivirus NNP cord-014597-66vd2mdu 149 2 and and CC cord-014597-66vd2mdu 149 3 AAV AAV NNP cord-014597-66vd2mdu 149 4 production production NN cord-014597-66vd2mdu 149 5 . . . cord-014597-66vd2mdu 150 1 Irrespective irrespective RB cord-014597-66vd2mdu 150 2 of of IN cord-014597-66vd2mdu 150 3 the the DT cord-014597-66vd2mdu 150 4 cell cell NN cord-014597-66vd2mdu 150 5 culture culture NN cord-014597-66vd2mdu 150 6 vessel vessel NN cord-014597-66vd2mdu 150 7 type type NN cord-014597-66vd2mdu 150 8 , , , cord-014597-66vd2mdu 150 9 transfection transfection NN cord-014597-66vd2mdu 150 10 using use VBG cord-014597-66vd2mdu 150 11 PEIpro PEIpro NNP cord-014597-66vd2mdu 150 12 ® ® NNP cord-014597-66vd2mdu 150 13 was be VBD cord-014597-66vd2mdu 150 14 performed perform VBN cord-014597-66vd2mdu 150 15 following follow VBG cord-014597-66vd2mdu 150 16 our -PRON- PRP$ cord-014597-66vd2mdu 150 17 recommandations recommandation NNS cord-014597-66vd2mdu 150 18 . . . cord-014597-66vd2mdu 151 1 As as IN cord-014597-66vd2mdu 151 2 an an DT cord-014597-66vd2mdu 151 3 example example NN cord-014597-66vd2mdu 151 4 , , , cord-014597-66vd2mdu 151 5 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 151 6 T T NNP cord-014597-66vd2mdu 151 7 ( ( -LRB- cord-014597-66vd2mdu 151 8 lentivirus lentivirus NN cord-014597-66vd2mdu 151 9 ) ) -RRB- cord-014597-66vd2mdu 151 10 and and CC cord-014597-66vd2mdu 151 11 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 151 12 ( ( -LRB- cord-014597-66vd2mdu 151 13 AAV AAV NNP cord-014597-66vd2mdu 151 14 ) ) -RRB- cord-014597-66vd2mdu 151 15 cells cell NNS cord-014597-66vd2mdu 151 16 were be VBD cord-014597-66vd2mdu 151 17 thawed thaw VBN cord-014597-66vd2mdu 151 18 directly directly RB cord-014597-66vd2mdu 151 19 into into IN cord-014597-66vd2mdu 151 20 each each DT cord-014597-66vd2mdu 151 21 medium medium NN cord-014597-66vd2mdu 151 22 and and CC cord-014597-66vd2mdu 151 23 passaged passage VBD cord-014597-66vd2mdu 151 24 every every DT cord-014597-66vd2mdu 151 25 3 3 CD cord-014597-66vd2mdu 151 26 to to TO cord-014597-66vd2mdu 151 27 4 4 CD cord-014597-66vd2mdu 151 28 days day NNS cord-014597-66vd2mdu 151 29 before before IN cord-014597-66vd2mdu 151 30 going go VBG cord-014597-66vd2mdu 151 31 into into IN cord-014597-66vd2mdu 151 32 a a DT cord-014597-66vd2mdu 151 33 2 2 CD cord-014597-66vd2mdu 151 34 Liter liter NN cord-014597-66vd2mdu 151 35 benchtop benchtop NN cord-014597-66vd2mdu 151 36 bioreactor bioreactor NN cord-014597-66vd2mdu 151 37 . . . cord-014597-66vd2mdu 152 1 Cells cell NNS cord-014597-66vd2mdu 152 2 were be VBD cord-014597-66vd2mdu 152 3 resuspended resuspend VBN cord-014597-66vd2mdu 152 4 and and CC cord-014597-66vd2mdu 152 5 cultured culture VBN cord-014597-66vd2mdu 152 6 for for IN cord-014597-66vd2mdu 152 7 3 3 CD cord-014597-66vd2mdu 152 8 days day NNS cord-014597-66vd2mdu 152 9 before before IN cord-014597-66vd2mdu 152 10 transfection transfection NN cord-014597-66vd2mdu 152 11 with with IN cord-014597-66vd2mdu 152 12 PEIpro PEIpro NNP cord-014597-66vd2mdu 152 13 ® ® NNPS cord-014597-66vd2mdu 152 14 . . . cord-014597-66vd2mdu 153 1 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 154 1 T t NN cord-014597-66vd2mdu 154 2 cells cell NNS cord-014597-66vd2mdu 154 3 were be VBD cord-014597-66vd2mdu 154 4 transfected transfecte VBN cord-014597-66vd2mdu 154 5 with with IN cord-014597-66vd2mdu 154 6 a a DT cord-014597-66vd2mdu 154 7 third third JJ cord-014597-66vd2mdu 154 8 - - HYPH cord-014597-66vd2mdu 154 9 generation generation NN cord-014597-66vd2mdu 154 10 system system NN cord-014597-66vd2mdu 154 11 ( ( -LRB- cord-014597-66vd2mdu 154 12 four four CD cord-014597-66vd2mdu 154 13 plasmids plasmid NNS cord-014597-66vd2mdu 154 14 ) ) -RRB- cord-014597-66vd2mdu 154 15 for for IN cord-014597-66vd2mdu 154 16 lentivirus lentivirus NN cord-014597-66vd2mdu 154 17 production production NN cord-014597-66vd2mdu 154 18 . . . cord-014597-66vd2mdu 155 1 HEK-293 hek-293 JJ cord-014597-66vd2mdu 155 2 cells cell NNS cord-014597-66vd2mdu 155 3 were be VBD cord-014597-66vd2mdu 155 4 co co JJ cord-014597-66vd2mdu 155 5 - - VBN cord-014597-66vd2mdu 155 6 transfected transfecte VBN cord-014597-66vd2mdu 155 7 with with IN cord-014597-66vd2mdu 155 8 three three CD cord-014597-66vd2mdu 155 9 plasmids plasmid NNS cord-014597-66vd2mdu 155 10 for for IN cord-014597-66vd2mdu 155 11 AAV AAV NNP cord-014597-66vd2mdu 155 12 production production NN cord-014597-66vd2mdu 155 13 . . . cord-014597-66vd2mdu 156 1 Lentiviral Lentiviral NNP cord-014597-66vd2mdu 156 2 and and CC cord-014597-66vd2mdu 156 3 AAV AAV NNP cord-014597-66vd2mdu 156 4 titers titer NNS cord-014597-66vd2mdu 156 5 were be VBD cord-014597-66vd2mdu 156 6 measured measure VBN cord-014597-66vd2mdu 156 7 48 48 CD cord-014597-66vd2mdu 156 8 and and CC cord-014597-66vd2mdu 156 9 72 72 CD cord-014597-66vd2mdu 156 10 hours hour NNS cord-014597-66vd2mdu 156 11 post post NN cord-014597-66vd2mdu 156 12 - - NN cord-014597-66vd2mdu 156 13 transfection transfection JJ cord-014597-66vd2mdu 157 1 ( ( -LRB- cord-014597-66vd2mdu 157 2 Data Data NNP cord-014597-66vd2mdu 157 3 kindly kindly RB cord-014597-66vd2mdu 157 4 provided provide VBN cord-014597-66vd2mdu 157 5 by by IN cord-014597-66vd2mdu 157 6 Généthon Généthon NNP cord-014597-66vd2mdu 157 7 ) ) -RRB- cord-014597-66vd2mdu 157 8 . . . cord-014597-66vd2mdu 158 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 159 1 ® ® NNP cord-014597-66vd2mdu 159 2 is be VBZ cord-014597-66vd2mdu 159 3 the the DT cord-014597-66vd2mdu 159 4 reagent reagent NN cord-014597-66vd2mdu 159 5 of of IN cord-014597-66vd2mdu 159 6 choice choice NN cord-014597-66vd2mdu 159 7 for for IN cord-014597-66vd2mdu 159 8 virus virus NN cord-014597-66vd2mdu 159 9 production production NN cord-014597-66vd2mdu 159 10 runs run VBZ cord-014597-66vd2mdu 159 11 in in IN cord-014597-66vd2mdu 159 12 most most RBS cord-014597-66vd2mdu 159 13 adherent adherent JJ cord-014597-66vd2mdu 159 14 and and CC cord-014597-66vd2mdu 159 15 suspension suspension NN cord-014597-66vd2mdu 159 16 cell cell NN cord-014597-66vd2mdu 159 17 culture culture NN cord-014597-66vd2mdu 159 18 systems system NNS cord-014597-66vd2mdu 159 19 from from IN cord-014597-66vd2mdu 159 20 process process NN cord-014597-66vd2mdu 159 21 development development NN cord-014597-66vd2mdu 159 22 up up IN cord-014597-66vd2mdu 159 23 to to IN cord-014597-66vd2mdu 159 24 large large JJ cord-014597-66vd2mdu 159 25 scale scale NN cord-014597-66vd2mdu 159 26 clinical clinical JJ cord-014597-66vd2mdu 159 27 - - HYPH cord-014597-66vd2mdu 159 28 grade grade NN cord-014597-66vd2mdu 159 29 virus virus NN cord-014597-66vd2mdu 159 30 production production NN cord-014597-66vd2mdu 159 31 . . . cord-014597-66vd2mdu 160 1 Irrespective irrespective RB cord-014597-66vd2mdu 160 2 of of IN cord-014597-66vd2mdu 160 3 the the DT cord-014597-66vd2mdu 160 4 cell cell NN cord-014597-66vd2mdu 160 5 culture culture NN cord-014597-66vd2mdu 160 6 - - HYPH cord-014597-66vd2mdu 160 7 based base VBN cord-014597-66vd2mdu 160 8 system system NN cord-014597-66vd2mdu 160 9 and and CC cord-014597-66vd2mdu 160 10 production production NN cord-014597-66vd2mdu 160 11 scale scale NN cord-014597-66vd2mdu 160 12 , , , cord-014597-66vd2mdu 161 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 161 2 ® ® VBP cord-014597-66vd2mdu 161 3 and and CC cord-014597-66vd2mdu 161 4 PEIpro PEIpro NNP cord-014597-66vd2mdu 161 5 ® ® NNPS cord-014597-66vd2mdu 161 6 -HQ -hq RB cord-014597-66vd2mdu 161 7 have have VBP cord-014597-66vd2mdu 161 8 led lead VBN cord-014597-66vd2mdu 161 9 to to IN cord-014597-66vd2mdu 161 10 efficient efficient JJ cord-014597-66vd2mdu 161 11 viral viral JJ cord-014597-66vd2mdu 161 12 vector vector NN cord-014597-66vd2mdu 161 13 yields yield NNS cord-014597-66vd2mdu 161 14 in in IN cord-014597-66vd2mdu 161 15 standard standard JJ cord-014597-66vd2mdu 161 16 laboratory laboratory NN cord-014597-66vd2mdu 161 17 cell cell NN cord-014597-66vd2mdu 161 18 systems system NNS cord-014597-66vd2mdu 161 19 , , , cord-014597-66vd2mdu 161 20 such such JJ cord-014597-66vd2mdu 161 21 as as IN cord-014597-66vd2mdu 161 22 in in IN cord-014597-66vd2mdu 161 23 flasks flask NNS cord-014597-66vd2mdu 161 24 , , , cord-014597-66vd2mdu 161 25 cell cell NN cord-014597-66vd2mdu 161 26 factories factory NNS cord-014597-66vd2mdu 161 27 , , , cord-014597-66vd2mdu 161 28 and and CC cord-014597-66vd2mdu 161 29 roller roller NN cord-014597-66vd2mdu 161 30 bottles bottle NNS cord-014597-66vd2mdu 161 31 , , , cord-014597-66vd2mdu 161 32 as as RB cord-014597-66vd2mdu 161 33 well well RB cord-014597-66vd2mdu 161 34 as as IN cord-014597-66vd2mdu 161 35 in in IN cord-014597-66vd2mdu 161 36 multilayers multilayer NNS cord-014597-66vd2mdu 161 37 flasks flask NNS cord-014597-66vd2mdu 161 38 or or CC cord-014597-66vd2mdu 161 39 fixed fix VBN cord-014597-66vd2mdu 161 40 - - HYPH cord-014597-66vd2mdu 161 41 bed bed NN cord-014597-66vd2mdu 161 42 culture culture NN cord-014597-66vd2mdu 161 43 systems system NNS cord-014597-66vd2mdu 161 44 that that WDT cord-014597-66vd2mdu 161 45 take take VBP cord-014597-66vd2mdu 161 46 into into IN cord-014597-66vd2mdu 161 47 account account NN cord-014597-66vd2mdu 161 48 time time NN cord-014597-66vd2mdu 161 49 and and CC cord-014597-66vd2mdu 161 50 space space NN cord-014597-66vd2mdu 161 51 concerns concern NNS cord-014597-66vd2mdu 161 52 for for IN cord-014597-66vd2mdu 161 53 the the DT cord-014597-66vd2mdu 161 54 scaling scale VBG cord-014597-66vd2mdu 161 55 - - HYPH cord-014597-66vd2mdu 161 56 up up RP cord-014597-66vd2mdu 161 57 process process NN cord-014597-66vd2mdu 161 58 ( ( -LRB- cord-014597-66vd2mdu 161 59 Table table NN cord-014597-66vd2mdu 161 60 1 1 CD cord-014597-66vd2mdu 161 61 ) ) -RRB- cord-014597-66vd2mdu 161 62 . . . cord-014597-66vd2mdu 162 1 For for IN cord-014597-66vd2mdu 162 2 example example NN cord-014597-66vd2mdu 162 3 , , , cord-014597-66vd2mdu 162 4 high high JJ cord-014597-66vd2mdu 162 5 viral viral JJ cord-014597-66vd2mdu 162 6 vector vector NN cord-014597-66vd2mdu 162 7 yields yield NNS cord-014597-66vd2mdu 162 8 superior superior JJ cord-014597-66vd2mdu 162 9 to to IN cord-014597-66vd2mdu 162 10 10 10 CD cord-014597-66vd2mdu 162 11 7 7 CD cord-014597-66vd2mdu 162 12 IG ig NN cord-014597-66vd2mdu 162 13 / / SYM cord-014597-66vd2mdu 162 14 mL ml NN cord-014597-66vd2mdu 162 15 and and CC cord-014597-66vd2mdu 162 16 10 10 CD cord-014597-66vd2mdu 162 17 11 11 CD cord-014597-66vd2mdu 162 18 -10 -10 CD cord-014597-66vd2mdu 162 19 12 12 CD cord-014597-66vd2mdu 162 20 VG VG NNP cord-014597-66vd2mdu 162 21 / / SYM cord-014597-66vd2mdu 162 22 mL ml NN cord-014597-66vd2mdu 162 23 were be VBD cord-014597-66vd2mdu 162 24 obtained obtain VBN cord-014597-66vd2mdu 162 25 respectively respectively RB cord-014597-66vd2mdu 162 26 for for IN cord-014597-66vd2mdu 162 27 lentiviruses lentiviruse NNS cord-014597-66vd2mdu 162 28 and and CC cord-014597-66vd2mdu 162 29 AAVs aav NNS cord-014597-66vd2mdu 162 30 in in IN cord-014597-66vd2mdu 162 31 suspension suspension NN cord-014597-66vd2mdu 162 32 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 162 33 T T NNP cord-014597-66vd2mdu 162 34 and and CC cord-014597-66vd2mdu 162 35 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 162 36 cells cell NNS cord-014597-66vd2mdu 162 37 cultured culture VBN cord-014597-66vd2mdu 162 38 in in IN cord-014597-66vd2mdu 162 39 one one CD cord-014597-66vd2mdu 162 40 of of IN cord-014597-66vd2mdu 162 41 the the DT cord-014597-66vd2mdu 162 42 commercially commercially RB cord-014597-66vd2mdu 162 43 available available JJ cord-014597-66vd2mdu 162 44 synthetic synthetic JJ cord-014597-66vd2mdu 162 45 cell cell NN cord-014597-66vd2mdu 162 46 culture culture NN cord-014597-66vd2mdu 162 47 medium medium NN cord-014597-66vd2mdu 162 48 BalanCD BalanCD NNP cord-014597-66vd2mdu 162 49 ® ® POS cord-014597-66vd2mdu 162 50 HEK293 HEK293 NNP cord-014597-66vd2mdu 163 1 ( ( -LRB- cord-014597-66vd2mdu 163 2 Irvine Irvine NNP cord-014597-66vd2mdu 163 3 Scientific Scientific NNP cord-014597-66vd2mdu 163 4 ® ® NNP cord-014597-66vd2mdu 163 5 ) ) -RRB- cord-014597-66vd2mdu 163 6 . . . cord-014597-66vd2mdu 164 1 Conclusion Conclusion NNP cord-014597-66vd2mdu 164 2 PEIpro PEIpro NNP cord-014597-66vd2mdu 164 3 ® ® NN cord-014597-66vd2mdu 164 4 and and CC cord-014597-66vd2mdu 164 5 its -PRON- PRP$ cord-014597-66vd2mdu 164 6 higher high JJR cord-014597-66vd2mdu 164 7 quality quality NN cord-014597-66vd2mdu 164 8 grade grade NN cord-014597-66vd2mdu 165 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 166 1 ® ® , cord-014597-66vd2mdu 166 2 -HQ -hq CC cord-014597-66vd2mdu 166 3 are be VBP cord-014597-66vd2mdu 166 4 the the DT cord-014597-66vd2mdu 166 5 unique unique JJ cord-014597-66vd2mdu 166 6 PEI PEI NNP cord-014597-66vd2mdu 166 7 suitable suitable JJ cord-014597-66vd2mdu 166 8 for for IN cord-014597-66vd2mdu 166 9 efficient efficient JJ cord-014597-66vd2mdu 166 10 and and CC cord-014597-66vd2mdu 166 11 reproducible reproducible JJ cord-014597-66vd2mdu 166 12 production production NN cord-014597-66vd2mdu 166 13 of of IN cord-014597-66vd2mdu 166 14 therapeutic therapeutic JJ cord-014597-66vd2mdu 166 15 viral viral JJ cord-014597-66vd2mdu 166 16 vectors vector NNS cord-014597-66vd2mdu 166 17 . . . cord-014597-66vd2mdu 167 1 Efficient efficient JJ cord-014597-66vd2mdu 167 2 viral viral JJ cord-014597-66vd2mdu 167 3 vector vector NN cord-014597-66vd2mdu 167 4 production production NN cord-014597-66vd2mdu 167 5 yields yield NNS cord-014597-66vd2mdu 167 6 can can MD cord-014597-66vd2mdu 167 7 be be VB cord-014597-66vd2mdu 167 8 achieved achieve VBN cord-014597-66vd2mdu 167 9 in in IN cord-014597-66vd2mdu 167 10 most most JJS cord-014597-66vd2mdu 167 11 cell cell NN cord-014597-66vd2mdu 167 12 culture culture NN cord-014597-66vd2mdu 167 13 systems system NNS cord-014597-66vd2mdu 167 14 , , , cord-014597-66vd2mdu 167 15 irrespective irrespective RB cord-014597-66vd2mdu 167 16 of of IN cord-014597-66vd2mdu 167 17 the the DT cord-014597-66vd2mdu 167 18 production production NN cord-014597-66vd2mdu 167 19 scale scale NN cord-014597-66vd2mdu 167 20 . . . cord-014597-66vd2mdu 168 1 With with IN cord-014597-66vd2mdu 168 2 appropriate appropriate JJ cord-014597-66vd2mdu 168 3 and and CC cord-014597-66vd2mdu 168 4 advanced advanced JJ cord-014597-66vd2mdu 168 5 quality quality NN cord-014597-66vd2mdu 168 6 controls control NNS cord-014597-66vd2mdu 168 7 , , , cord-014597-66vd2mdu 168 8 the the DT cord-014597-66vd2mdu 168 9 highest high JJS cord-014597-66vd2mdu 168 10 quality quality NN cord-014597-66vd2mdu 168 11 grade grade NN cord-014597-66vd2mdu 168 12 PEIpro PEIpro NNP cord-014597-66vd2mdu 168 13 ® ® NNPS cord-014597-66vd2mdu 168 14 -HQ -hq NN cord-014597-66vd2mdu 168 15 is be VBZ cord-014597-66vd2mdu 168 16 commercially commercially RB cord-014597-66vd2mdu 168 17 available available JJ cord-014597-66vd2mdu 168 18 to to TO cord-014597-66vd2mdu 168 19 accompany accompany VB cord-014597-66vd2mdu 168 20 academics academic NNS cord-014597-66vd2mdu 168 21 and and CC cord-014597-66vd2mdu 168 22 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 168 23 companies company NNS cord-014597-66vd2mdu 168 24 in in IN cord-014597-66vd2mdu 168 25 terms term NNS cord-014597-66vd2mdu 168 26 of of IN cord-014597-66vd2mdu 168 27 qualified qualified JJ cord-014597-66vd2mdu 168 28 raw raw JJ cord-014597-66vd2mdu 168 29 material material NN cord-014597-66vd2mdu 168 30 for for IN cord-014597-66vd2mdu 168 31 their -PRON- PRP$ cord-014597-66vd2mdu 168 32 GMP GMP NNP cord-014597-66vd2mdu 168 33 - - HYPH cord-014597-66vd2mdu 168 34 grade grade NN cord-014597-66vd2mdu 168 35 viral viral JJ cord-014597-66vd2mdu 168 36 vector vector NN cord-014597-66vd2mdu 168 37 production production NN cord-014597-66vd2mdu 168 38 needs need NNS cord-014597-66vd2mdu 168 39 . . . cord-014597-66vd2mdu 169 1 b b LS cord-014597-66vd2mdu 169 2 Distinction distinction NN cord-014597-66vd2mdu 169 3 between between IN cord-014597-66vd2mdu 169 4 Fc Fc NNP cord-014597-66vd2mdu 169 5 and and CC cord-014597-66vd2mdu 169 6 Fab fab JJ cord-014597-66vd2mdu 169 7 glycosylation glycosylation NN cord-014597-66vd2mdu 169 8 in in IN cord-014597-66vd2mdu 169 9 Erbitux Erbitux NNP cord-014597-66vd2mdu 169 10 . . . cord-014597-66vd2mdu 170 1 Erbitux Erbitux NNP cord-014597-66vd2mdu 170 2 was be VBD cord-014597-66vd2mdu 170 3 diluted dilute VBN cord-014597-66vd2mdu 170 4 to to IN cord-014597-66vd2mdu 170 5 a a DT cord-014597-66vd2mdu 170 6 concentration concentration NN cord-014597-66vd2mdu 170 7 of of IN cord-014597-66vd2mdu 170 8 200 200 CD cord-014597-66vd2mdu 170 9 μg μg NN cord-014597-66vd2mdu 170 10 / / SYM cord-014597-66vd2mdu 170 11 mL ml NN cord-014597-66vd2mdu 170 12 in in IN cord-014597-66vd2mdu 170 13 TRIS TRIS NNP cord-014597-66vd2mdu 170 14 buffer buffer NN cord-014597-66vd2mdu 170 15 and and CC cord-014597-66vd2mdu 170 16 measured measure VBN cord-014597-66vd2mdu 170 17 in in IN cord-014597-66vd2mdu 170 18 native native JJ cord-014597-66vd2mdu 170 19 and and CC cord-014597-66vd2mdu 170 20 denatured denatured JJ cord-014597-66vd2mdu 170 21 conditions condition NNS cord-014597-66vd2mdu 170 22 to to TO cord-014597-66vd2mdu 170 23 distinguish distinguish VB cord-014597-66vd2mdu 170 24 Fab fab JJ cord-014597-66vd2mdu 170 25 glycosylation glycosylation NN cord-014597-66vd2mdu 170 26 ( ( -LRB- cord-014597-66vd2mdu 170 27 native native JJ cord-014597-66vd2mdu 170 28 Erbitux Erbitux NNP cord-014597-66vd2mdu 170 29 ) ) -RRB- cord-014597-66vd2mdu 170 30 from from IN cord-014597-66vd2mdu 170 31 Fab Fab NNP cord-014597-66vd2mdu 170 32 and and CC cord-014597-66vd2mdu 170 33 Fc Fc NNP cord-014597-66vd2mdu 170 34 glycosylation glycosylation NN cord-014597-66vd2mdu 170 35 ( ( -LRB- cord-014597-66vd2mdu 170 36 denatured denature VBN cord-014597-66vd2mdu 170 37 Erbitux Erbitux NNP cord-014597-66vd2mdu 170 38 ) ) -RRB- cord-014597-66vd2mdu 170 39 . . . cord-014597-66vd2mdu 171 1 It -PRON- PRP cord-014597-66vd2mdu 171 2 could could MD cord-014597-66vd2mdu 171 3 be be VB cord-014597-66vd2mdu 171 4 confirmed confirm VBN cord-014597-66vd2mdu 171 5 that that IN cord-014597-66vd2mdu 171 6 sialic sialic JJ cord-014597-66vd2mdu 171 7 acids acid NNS cord-014597-66vd2mdu 171 8 are be VBP cord-014597-66vd2mdu 171 9 almost almost RB cord-014597-66vd2mdu 171 10 exclusively exclusively RB cord-014597-66vd2mdu 171 11 present present JJ cord-014597-66vd2mdu 171 12 on on IN cord-014597-66vd2mdu 171 13 the the DT cord-014597-66vd2mdu 171 14 Fab fab JJ cord-014597-66vd2mdu 171 15 part part NN cord-014597-66vd2mdu 171 16 of of IN cord-014597-66vd2mdu 171 17 Erbitux Erbitux NNP cord-014597-66vd2mdu 171 18 and and CC cord-014597-66vd2mdu 171 19 that that IN cord-014597-66vd2mdu 171 20 the the DT cord-014597-66vd2mdu 171 21 high high JJ cord-014597-66vd2mdu 171 22 mannose mannose NN cord-014597-66vd2mdu 171 23 glycans glycan NNS cord-014597-66vd2mdu 171 24 are be VBP cord-014597-66vd2mdu 171 25 only only RB cord-014597-66vd2mdu 171 26 found find VBN cord-014597-66vd2mdu 171 27 in in IN cord-014597-66vd2mdu 171 28 the the DT cord-014597-66vd2mdu 171 29 Fc Fc NNP cord-014597-66vd2mdu 171 30 part part NN cord-014597-66vd2mdu 171 31 . . . cord-014597-66vd2mdu 172 1 c c LS cord-014597-66vd2mdu 172 2 Lectin Lectin NNP cord-014597-66vd2mdu 172 3 binding bind VBG cord-014597-66vd2mdu 172 4 rates rate NNS cord-014597-66vd2mdu 172 5 correlate correlate VBP cord-014597-66vd2mdu 172 6 with with IN cord-014597-66vd2mdu 172 7 the the DT cord-014597-66vd2mdu 172 8 levels level NNS cord-014597-66vd2mdu 172 9 of of IN cord-014597-66vd2mdu 172 10 galactosylation galactosylation NN cord-014597-66vd2mdu 172 11 and and CC cord-014597-66vd2mdu 172 12 fucosylation fucosylation NN cord-014597-66vd2mdu 172 13 . . . cord-014597-66vd2mdu 173 1 Two two CD cord-014597-66vd2mdu 173 2 glycan glycan NN cord-014597-66vd2mdu 173 3 variants variant NNS cord-014597-66vd2mdu 173 4 samples sample NNS cord-014597-66vd2mdu 173 5 of of IN cord-014597-66vd2mdu 173 6 the the DT cord-014597-66vd2mdu 173 7 same same JJ cord-014597-66vd2mdu 173 8 IgG igg NN cord-014597-66vd2mdu 173 9 from from IN cord-014597-66vd2mdu 173 10 Merck Merck NNP cord-014597-66vd2mdu 173 11 were be VBD cord-014597-66vd2mdu 173 12 mixed mix VBN cord-014597-66vd2mdu 173 13 in in IN cord-014597-66vd2mdu 173 14 different different JJ cord-014597-66vd2mdu 173 15 ratios ratio NNS cord-014597-66vd2mdu 173 16 to to TO cord-014597-66vd2mdu 173 17 yield yield VB cord-014597-66vd2mdu 173 18 glycosylation glycosylation NN cord-014597-66vd2mdu 173 19 rates rate NNS cord-014597-66vd2mdu 173 20 of of IN cord-014597-66vd2mdu 173 21 9 9 CD cord-014597-66vd2mdu 173 22 to to TO cord-014597-66vd2mdu 173 23 55 55 CD cord-014597-66vd2mdu 173 24 % % NN cord-014597-66vd2mdu 173 25 in in IN cord-014597-66vd2mdu 173 26 terminal terminal NN cord-014597-66vd2mdu 173 27 β β NN cord-014597-66vd2mdu 173 28 - - HYPH cord-014597-66vd2mdu 173 29 galactose galactose NN cord-014597-66vd2mdu 173 30 and and CC cord-014597-66vd2mdu 173 31 8 8 CD cord-014597-66vd2mdu 173 32 to to TO cord-014597-66vd2mdu 173 33 100 100 CD cord-014597-66vd2mdu 173 34 % % NN cord-014597-66vd2mdu 173 35 in in IN cord-014597-66vd2mdu 173 36 core core NN cord-014597-66vd2mdu 173 37 - - HYPH cord-014597-66vd2mdu 173 38 fucose fucose JJ cord-014597-66vd2mdu 173 39 , , , cord-014597-66vd2mdu 173 40 based base VBN cord-014597-66vd2mdu 173 41 on on IN cord-014597-66vd2mdu 173 42 data datum NNS cord-014597-66vd2mdu 173 43 from from IN cord-014597-66vd2mdu 173 44 2-AB 2-ab CD cord-014597-66vd2mdu 173 45 UPLC UPLC NNP cord-014597-66vd2mdu 173 46 analysis analysis NN cord-014597-66vd2mdu 173 47 . . . cord-014597-66vd2mdu 174 1 The the DT cord-014597-66vd2mdu 174 2 mixtures mixture NNS cord-014597-66vd2mdu 174 3 all all DT cord-014597-66vd2mdu 174 4 contained contain VBD cord-014597-66vd2mdu 174 5 0.5 0.5 CD cord-014597-66vd2mdu 174 6 μg μg NN cord-014597-66vd2mdu 174 7 IgG igg NN cord-014597-66vd2mdu 174 8 per per IN cord-014597-66vd2mdu 174 9 well well RB cord-014597-66vd2mdu 174 10 . . . cord-014597-66vd2mdu 175 1 The the DT cord-014597-66vd2mdu 175 2 measured measured JJ cord-014597-66vd2mdu 175 3 lectin lectin NN cord-014597-66vd2mdu 175 4 binding bind VBG cord-014597-66vd2mdu 175 5 rates rate NNS cord-014597-66vd2mdu 175 6 for for IN cord-014597-66vd2mdu 175 7 all all DT cord-014597-66vd2mdu 175 8 galactose galactose NN cord-014597-66vd2mdu 175 9 and and CC cord-014597-66vd2mdu 175 10 fucose fucose JJ cord-014597-66vd2mdu 175 11 markers marker NNS cord-014597-66vd2mdu 175 12 correlate correlate VBP cord-014597-66vd2mdu 175 13 very very RB cord-014597-66vd2mdu 175 14 well well RB cord-014597-66vd2mdu 175 15 with with IN cord-014597-66vd2mdu 175 16 the the DT cord-014597-66vd2mdu 175 17 respective respective JJ cord-014597-66vd2mdu 175 18 degree degree NN cord-014597-66vd2mdu 175 19 of of IN cord-014597-66vd2mdu 175 20 glycosylation glycosylation NN cord-014597-66vd2mdu 175 21 in in IN cord-014597-66vd2mdu 175 22 the the DT cord-014597-66vd2mdu 175 23 mixtures mixture NNS cord-014597-66vd2mdu 175 24 . . . cord-014597-66vd2mdu 176 1 All all DT cord-014597-66vd2mdu 176 2 measurements measurement NNS cord-014597-66vd2mdu 176 3 were be VBD cord-014597-66vd2mdu 176 4 performed perform VBN cord-014597-66vd2mdu 176 5 in in IN cord-014597-66vd2mdu 176 6 triplicates triplicate NNS cord-014597-66vd2mdu 176 7 ( ( -LRB- cord-014597-66vd2mdu 176 8 Irvine Irvine NNP cord-014597-66vd2mdu 176 9 _SP cord-014597-66vd2mdu 176 10 Scientific Scientific NNP cord-014597-66vd2mdu 176 11 ® ® NNP cord-014597-66vd2mdu 176 12 ) ) -RRB- cord-014597-66vd2mdu 176 13 . . . cord-014597-66vd2mdu 177 1 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 177 2 T T NNP cord-014597-66vd2mdu 177 3 ( ( -LRB- cord-014597-66vd2mdu 177 4 lentivirus lentivirus NN cord-014597-66vd2mdu 177 5 ) ) -RRB- cord-014597-66vd2mdu 177 6 and and CC cord-014597-66vd2mdu 177 7 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 177 8 ( ( -LRB- cord-014597-66vd2mdu 177 9 AAV AAV NNP cord-014597-66vd2mdu 177 10 ) ) -RRB- cord-014597-66vd2mdu 177 11 cells cell NNS cord-014597-66vd2mdu 177 12 were be VBD cord-014597-66vd2mdu 177 13 thawed thaw VBN cord-014597-66vd2mdu 177 14 directly directly RB cord-014597-66vd2mdu 177 15 into into IN cord-014597-66vd2mdu 177 16 each each DT cord-014597-66vd2mdu 177 17 medium medium NN cord-014597-66vd2mdu 177 18 and and CC cord-014597-66vd2mdu 177 19 passaged passage VBD cord-014597-66vd2mdu 177 20 every every DT cord-014597-66vd2mdu 177 21 3 3 CD cord-014597-66vd2mdu 177 22 to to TO cord-014597-66vd2mdu 177 23 4 4 CD cord-014597-66vd2mdu 177 24 days day NNS cord-014597-66vd2mdu 177 25 before before IN cord-014597-66vd2mdu 177 26 going go VBG cord-014597-66vd2mdu 177 27 into into IN cord-014597-66vd2mdu 177 28 a a DT cord-014597-66vd2mdu 177 29 2 2 CD cord-014597-66vd2mdu 177 30 Liter liter NN cord-014597-66vd2mdu 177 31 benchtop benchtop NN cord-014597-66vd2mdu 177 32 bioreactor bioreactor NN cord-014597-66vd2mdu 177 33 . . . cord-014597-66vd2mdu 178 1 Cells cell NNS cord-014597-66vd2mdu 178 2 were be VBD cord-014597-66vd2mdu 178 3 seeded seed VBN cord-014597-66vd2mdu 178 4 and and CC cord-014597-66vd2mdu 178 5 cultured culture VBN cord-014597-66vd2mdu 178 6 for for IN cord-014597-66vd2mdu 178 7 3 3 CD cord-014597-66vd2mdu 178 8 days day NNS cord-014597-66vd2mdu 178 9 before before IN cord-014597-66vd2mdu 178 10 being be VBG cord-014597-66vd2mdu 178 11 transfected transfecte VBN cord-014597-66vd2mdu 178 12 by by IN cord-014597-66vd2mdu 179 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 179 2 ® ® . cord-014597-66vd2mdu 179 3 ( ( -LRB- cord-014597-66vd2mdu 179 4 Polyplus Polyplus NNP cord-014597-66vd2mdu 179 5 ) ) -RRB- cord-014597-66vd2mdu 179 6 . . . cord-014597-66vd2mdu 180 1 For for IN cord-014597-66vd2mdu 180 2 transfection transfection NN cord-014597-66vd2mdu 180 3 , , , cord-014597-66vd2mdu 180 4 four four CD cord-014597-66vd2mdu 180 5 plasmids plasmid NNS cord-014597-66vd2mdu 180 6 were be VBD cord-014597-66vd2mdu 180 7 used use VBN cord-014597-66vd2mdu 180 8 for for IN cord-014597-66vd2mdu 180 9 lentivirus lentivirus NN cord-014597-66vd2mdu 180 10 and and CC cord-014597-66vd2mdu 180 11 three three CD cord-014597-66vd2mdu 180 12 plasmids plasmid NNS cord-014597-66vd2mdu 180 13 were be VBD cord-014597-66vd2mdu 180 14 used use VBN cord-014597-66vd2mdu 180 15 for for IN cord-014597-66vd2mdu 180 16 AAV AAV NNP cord-014597-66vd2mdu 180 17 . . . cord-014597-66vd2mdu 181 1 Lentiviral Lentiviral NNP cord-014597-66vd2mdu 181 2 and and CC cord-014597-66vd2mdu 181 3 AAV AAV NNP cord-014597-66vd2mdu 181 4 titer titer NN cord-014597-66vd2mdu 181 5 were be VBD cord-014597-66vd2mdu 181 6 measured measure VBN cord-014597-66vd2mdu 181 7 48 48 CD cord-014597-66vd2mdu 181 8 and and CC cord-014597-66vd2mdu 181 9 72 72 CD cord-014597-66vd2mdu 181 10 hours hour NNS cord-014597-66vd2mdu 181 11 post post NN cord-014597-66vd2mdu 181 12 transfection transfection NN cord-014597-66vd2mdu 182 1 ( ( -LRB- cord-014597-66vd2mdu 182 2 Data Data NNP cord-014597-66vd2mdu 182 3 kindly kindly RB cord-014597-66vd2mdu 182 4 provided provide VBN cord-014597-66vd2mdu 182 5 by by IN cord-014597-66vd2mdu 182 6 Généthon Généthon NNP cord-014597-66vd2mdu 182 7 ) ) -RRB- cord-014597-66vd2mdu 182 8 Table table NN cord-014597-66vd2mdu 182 9 1 1 CD cord-014597-66vd2mdu 182 10 ( ( -LRB- cord-014597-66vd2mdu 182 11 abstract abstract JJ cord-014597-66vd2mdu 182 12 P-004 P-004 NNP cord-014597-66vd2mdu 182 13 ) ) -RRB- cord-014597-66vd2mdu 182 14 . . . cord-014597-66vd2mdu 183 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 184 1 ® ® VB cord-014597-66vd2mdu 184 2 , , , cord-014597-66vd2mdu 184 3 the the DT cord-014597-66vd2mdu 184 4 reagent reagent NN cord-014597-66vd2mdu 184 5 of of IN cord-014597-66vd2mdu 184 6 choice choice NN cord-014597-66vd2mdu 184 7 for for IN cord-014597-66vd2mdu 184 8 virus virus NN cord-014597-66vd2mdu 184 9 production production NN cord-014597-66vd2mdu 184 10 runs run VBZ cord-014597-66vd2mdu 184 11 in in IN cord-014597-66vd2mdu 184 12 most most JJS cord-014597-66vd2mdu 184 13 cell cell NN cord-014597-66vd2mdu 184 14 culture culture NN cord-014597-66vd2mdu 184 15 systems system NNS cord-014597-66vd2mdu 184 16 in in IN cord-014597-66vd2mdu 184 17 both both CC cord-014597-66vd2mdu 184 18 adherent adherent JJ cord-014597-66vd2mdu 184 19 and and CC cord-014597-66vd2mdu 184 20 suspension suspension NN cord-014597-66vd2mdu 184 21 cells cell NNS cord-014597-66vd2mdu 184 22 . . . cord-014597-66vd2mdu 185 1 Irrespective irrespective RB cord-014597-66vd2mdu 185 2 of of IN cord-014597-66vd2mdu 185 3 the the DT cord-014597-66vd2mdu 185 4 cell cell NN cord-014597-66vd2mdu 185 5 culture culture NN cord-014597-66vd2mdu 185 6 - - HYPH cord-014597-66vd2mdu 185 7 based base VBN cord-014597-66vd2mdu 185 8 system system NN cord-014597-66vd2mdu 185 9 and and CC cord-014597-66vd2mdu 185 10 production production NN cord-014597-66vd2mdu 185 11 scale scale NN cord-014597-66vd2mdu 185 12 , , , cord-014597-66vd2mdu 186 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 186 2 ® ® VBP cord-014597-66vd2mdu 186 3 and and CC cord-014597-66vd2mdu 186 4 PEIpro PEIpro NNP cord-014597-66vd2mdu 186 5 ® ® NNPS cord-014597-66vd2mdu 186 6 -HQ -hq RB cord-014597-66vd2mdu 186 7 have have VBP cord-014597-66vd2mdu 186 8 led lead VBN cord-014597-66vd2mdu 186 9 to to IN cord-014597-66vd2mdu 186 10 efficient efficient JJ cord-014597-66vd2mdu 186 11 viral viral JJ cord-014597-66vd2mdu 186 12 vector vector NN cord-014597-66vd2mdu 186 13 yields yield NNS cord-014597-66vd2mdu 186 14 superior superior JJ cord-014597-66vd2mdu 186 15 to to IN cord-014597-66vd2mdu 186 16 10 10 CD cord-014597-66vd2mdu 186 17 7 7 CD cord-014597-66vd2mdu 186 18 IG ig NN cord-014597-66vd2mdu 186 19 / / SYM cord-014597-66vd2mdu 186 20 mL ml NN cord-014597-66vd2mdu 186 21 and and CC cord-014597-66vd2mdu 186 22 10 10 CD cord-014597-66vd2mdu 186 23 9 9 CD cord-014597-66vd2mdu 186 24 VG VG NNP cord-014597-66vd2mdu 186 25 / / SYM cord-014597-66vd2mdu 186 26 mL ml NN cord-014597-66vd2mdu 186 27 , , , cord-014597-66vd2mdu 186 28 respectively respectively RB cord-014597-66vd2mdu 186 29 for for IN cord-014597-66vd2mdu 186 30 lentiviruses lentiviruse NNS cord-014597-66vd2mdu 186 31 and and CC cord-014597-66vd2mdu 186 32 AAVs AAVs NNPS cord-014597-66vd2mdu 186 33 Background Background NNP cord-014597-66vd2mdu 186 34 Continuous continuous JJ cord-014597-66vd2mdu 186 35 perfusion perfusion NN cord-014597-66vd2mdu 186 36 process process NN cord-014597-66vd2mdu 186 37 is be VBZ cord-014597-66vd2mdu 186 38 making make VBG cord-014597-66vd2mdu 186 39 a a DT cord-014597-66vd2mdu 186 40 comeback comeback NN cord-014597-66vd2mdu 186 41 as as IN cord-014597-66vd2mdu 186 42 a a DT cord-014597-66vd2mdu 186 43 competing compete VBG cord-014597-66vd2mdu 186 44 upstream upstream JJ cord-014597-66vd2mdu 186 45 manufacturing manufacturing NN cord-014597-66vd2mdu 186 46 technology technology NN cord-014597-66vd2mdu 186 47 for for IN cord-014597-66vd2mdu 186 48 the the DT cord-014597-66vd2mdu 186 49 production production NN cord-014597-66vd2mdu 186 50 of of IN cord-014597-66vd2mdu 186 51 Biopharmaceuticals Biopharmaceuticals NNPS cord-014597-66vd2mdu 186 52 compared compare VBN cord-014597-66vd2mdu 186 53 to to IN cord-014597-66vd2mdu 186 54 the the DT cord-014597-66vd2mdu 186 55 standard standard JJ cord-014597-66vd2mdu 186 56 fed fed NNP cord-014597-66vd2mdu 186 57 batch batch NN cord-014597-66vd2mdu 186 58 processes process NNS cord-014597-66vd2mdu 186 59 . . . cord-014597-66vd2mdu 187 1 This this DT cord-014597-66vd2mdu 187 2 is be VBZ cord-014597-66vd2mdu 187 3 primarily primarily RB cord-014597-66vd2mdu 187 4 because because IN cord-014597-66vd2mdu 187 5 of of IN cord-014597-66vd2mdu 187 6 cost cost NN cord-014597-66vd2mdu 187 7 advantages advantage NNS cord-014597-66vd2mdu 187 8 such such JJ cord-014597-66vd2mdu 187 9 as as IN cord-014597-66vd2mdu 187 10 reduced reduce VBN cord-014597-66vd2mdu 187 11 capital capital NN cord-014597-66vd2mdu 187 12 cost cost NN cord-014597-66vd2mdu 187 13 and and CC cord-014597-66vd2mdu 187 14 increased increase VBN cord-014597-66vd2mdu 187 15 product product NN cord-014597-66vd2mdu 187 16 yield yield NN cord-014597-66vd2mdu 187 17 . . . cord-014597-66vd2mdu 188 1 The the DT cord-014597-66vd2mdu 188 2 change change NN cord-014597-66vd2mdu 188 3 in in IN cord-014597-66vd2mdu 188 4 status status NN cord-014597-66vd2mdu 188 5 of of IN cord-014597-66vd2mdu 188 6 perfusion perfusion NN cord-014597-66vd2mdu 188 7 process process NN cord-014597-66vd2mdu 188 8 from from IN cord-014597-66vd2mdu 188 9 older old JJR cord-014597-66vd2mdu 188 10 perfusion perfusion NN cord-014597-66vd2mdu 188 11 to to IN cord-014597-66vd2mdu 188 12 the the DT cord-014597-66vd2mdu 188 13 new new JJ cord-014597-66vd2mdu 188 14 - - HYPH cord-014597-66vd2mdu 188 15 age age NN cord-014597-66vd2mdu 188 16 perfusion perfusion NN cord-014597-66vd2mdu 188 17 is be VBZ cord-014597-66vd2mdu 188 18 due due JJ cord-014597-66vd2mdu 188 19 to to IN cord-014597-66vd2mdu 188 20 availability availability NN cord-014597-66vd2mdu 188 21 of of IN cord-014597-66vd2mdu 188 22 better well JJR cord-014597-66vd2mdu 188 23 cell cell NN cord-014597-66vd2mdu 188 24 retention retention NN cord-014597-66vd2mdu 188 25 devices device NNS cord-014597-66vd2mdu 188 26 leading lead VBG cord-014597-66vd2mdu 188 27 to to IN cord-014597-66vd2mdu 188 28 more more RBR cord-014597-66vd2mdu 188 29 efficient efficient JJ cord-014597-66vd2mdu 188 30 processes process NNS cord-014597-66vd2mdu 188 31 , , , cord-014597-66vd2mdu 188 32 improved improved JJ cord-014597-66vd2mdu 188 33 cell cell NN cord-014597-66vd2mdu 188 34 lines line NNS cord-014597-66vd2mdu 188 35 , , , cord-014597-66vd2mdu 188 36 cell cell NN cord-014597-66vd2mdu 188 37 culture culture NN cord-014597-66vd2mdu 188 38 medium medium NN cord-014597-66vd2mdu 188 39 capable capable JJ cord-014597-66vd2mdu 188 40 of of IN cord-014597-66vd2mdu 188 41 supporting support VBG cord-014597-66vd2mdu 188 42 high high JJ cord-014597-66vd2mdu 188 43 cell cell NN cord-014597-66vd2mdu 188 44 densities density NNS cord-014597-66vd2mdu 188 45 and and CC cord-014597-66vd2mdu 188 46 better well JJR cord-014597-66vd2mdu 188 47 bioreactor bioreactor NN cord-014597-66vd2mdu 188 48 control control NN cord-014597-66vd2mdu 188 49 strategies strategy NNS cord-014597-66vd2mdu 188 50 . . . cord-014597-66vd2mdu 189 1 In in IN cord-014597-66vd2mdu 189 2 this this DT cord-014597-66vd2mdu 189 3 work work NN cord-014597-66vd2mdu 189 4 , , , cord-014597-66vd2mdu 189 5 we -PRON- PRP cord-014597-66vd2mdu 189 6 present present VBP cord-014597-66vd2mdu 189 7 the the DT cord-014597-66vd2mdu 189 8 advantages advantage NNS cord-014597-66vd2mdu 189 9 , , , cord-014597-66vd2mdu 189 10 limitations limitation NNS cord-014597-66vd2mdu 189 11 and and CC cord-014597-66vd2mdu 189 12 challenges challenge NNS cord-014597-66vd2mdu 189 13 of of IN cord-014597-66vd2mdu 189 14 fed fed NNP cord-014597-66vd2mdu 189 15 batch batch NN cord-014597-66vd2mdu 189 16 and and CC cord-014597-66vd2mdu 189 17 perfusion perfusion NN cord-014597-66vd2mdu 189 18 type type NN cord-014597-66vd2mdu 189 19 of of IN cord-014597-66vd2mdu 189 20 processes process NNS cord-014597-66vd2mdu 189 21 through through IN cord-014597-66vd2mdu 189 22 case case NN cord-014597-66vd2mdu 189 23 studies study NNS cord-014597-66vd2mdu 189 24 . . . cord-014597-66vd2mdu 190 1 Table table NN cord-014597-66vd2mdu 190 2 1 1 CD cord-014597-66vd2mdu 190 3 Results result NNS cord-014597-66vd2mdu 191 1 The the DT cord-014597-66vd2mdu 191 2 Perfusion perfusion NN cord-014597-66vd2mdu 191 3 run run NN cord-014597-66vd2mdu 191 4 yielded yield VBD cord-014597-66vd2mdu 191 5 5-fold 5-fold CD cord-014597-66vd2mdu 191 6 higher high JJR cord-014597-66vd2mdu 191 7 titer titer NN cord-014597-66vd2mdu 191 8 compared compare VBN cord-014597-66vd2mdu 191 9 to to IN cord-014597-66vd2mdu 191 10 Fed Fed NNP cord-014597-66vd2mdu 191 11 batch batch NN cord-014597-66vd2mdu 191 12 run run NN cord-014597-66vd2mdu 191 13 ( ( -LRB- cord-014597-66vd2mdu 191 14 Fig fig NN cord-014597-66vd2mdu 191 15 . . . cord-014597-66vd2mdu 191 16 1a 1a CD cord-014597-66vd2mdu 191 17 ) ) -RRB- cord-014597-66vd2mdu 191 18 . . . cord-014597-66vd2mdu 192 1 Considering consider VBG cord-014597-66vd2mdu 192 2 the the DT cord-014597-66vd2mdu 192 3 number number NN cord-014597-66vd2mdu 192 4 of of IN cord-014597-66vd2mdu 192 5 runs run NNS cord-014597-66vd2mdu 192 6 that that WDT cord-014597-66vd2mdu 192 7 could could MD cord-014597-66vd2mdu 192 8 be be VB cord-014597-66vd2mdu 192 9 executed execute VBN cord-014597-66vd2mdu 192 10 in in IN cord-014597-66vd2mdu 192 11 a a DT cord-014597-66vd2mdu 192 12 manufacturing manufacturing NN cord-014597-66vd2mdu 192 13 facility facility NN cord-014597-66vd2mdu 192 14 within within IN cord-014597-66vd2mdu 192 15 the the DT cord-014597-66vd2mdu 192 16 same same JJ cord-014597-66vd2mdu 192 17 calendar calendar NN cord-014597-66vd2mdu 192 18 days day NNS cord-014597-66vd2mdu 192 19 , , , cord-014597-66vd2mdu 192 20 about about RB cord-014597-66vd2mdu 192 21 1fold 1fold CD cord-014597-66vd2mdu 192 22 increase increase NN cord-014597-66vd2mdu 192 23 in in IN cord-014597-66vd2mdu 192 24 product product NN cord-014597-66vd2mdu 192 25 output output NN cord-014597-66vd2mdu 192 26 can can MD cord-014597-66vd2mdu 192 27 be be VB cord-014597-66vd2mdu 192 28 achieved achieve VBN cord-014597-66vd2mdu 192 29 with with IN cord-014597-66vd2mdu 192 30 the the DT cord-014597-66vd2mdu 192 31 perfusion perfusion NN cord-014597-66vd2mdu 192 32 process process NN cord-014597-66vd2mdu 192 33 ( ( -LRB- cord-014597-66vd2mdu 192 34 Fig Fig NNP cord-014597-66vd2mdu 192 35 . . . cord-014597-66vd2mdu 192 36 1a 1a CD cord-014597-66vd2mdu 192 37 ) ) -RRB- cord-014597-66vd2mdu 192 38 . . . cord-014597-66vd2mdu 193 1 This this DT cord-014597-66vd2mdu 193 2 difference difference NN cord-014597-66vd2mdu 193 3 is be VBZ cord-014597-66vd2mdu 193 4 attributed attribute VBN cord-014597-66vd2mdu 193 5 to to IN cord-014597-66vd2mdu 193 6 higher high JJR cord-014597-66vd2mdu 193 7 IVCC IVCC NNP cord-014597-66vd2mdu 193 8 , , , cord-014597-66vd2mdu 193 9 higher high JJR cord-014597-66vd2mdu 193 10 PCD PCD NNP cord-014597-66vd2mdu 193 11 and and CC cord-014597-66vd2mdu 193 12 longevity longevity NN cord-014597-66vd2mdu 193 13 of of IN cord-014597-66vd2mdu 193 14 cells cell NNS cord-014597-66vd2mdu 193 15 because because IN cord-014597-66vd2mdu 193 16 of of IN cord-014597-66vd2mdu 193 17 decreased decreased JJ cord-014597-66vd2mdu 193 18 level level NN cord-014597-66vd2mdu 193 19 of of IN cord-014597-66vd2mdu 193 20 toxic toxic JJ cord-014597-66vd2mdu 193 21 metabolite metabolite JJ cord-014597-66vd2mdu 193 22 concentrations concentration NNS cord-014597-66vd2mdu 193 23 such such JJ cord-014597-66vd2mdu 193 24 as as IN cord-014597-66vd2mdu 193 25 lactate lactate NN cord-014597-66vd2mdu 193 26 and and CC cord-014597-66vd2mdu 193 27 ammonia ammonia NN cord-014597-66vd2mdu 193 28 . . . cord-014597-66vd2mdu 194 1 Case case NN cord-014597-66vd2mdu 194 2 2 2 CD cord-014597-66vd2mdu 194 3 : : : cord-014597-66vd2mdu 195 1 Understanding understand VBG cord-014597-66vd2mdu 195 2 product product NN cord-014597-66vd2mdu 195 3 retention retention NN cord-014597-66vd2mdu 195 4 in in IN cord-014597-66vd2mdu 195 5 perfusion perfusion NN cord-014597-66vd2mdu 195 6 process process NN cord-014597-66vd2mdu 196 1 The the DT cord-014597-66vd2mdu 196 2 new new JJ cord-014597-66vd2mdu 196 3 - - HYPH cord-014597-66vd2mdu 196 4 age age NN cord-014597-66vd2mdu 196 5 perfusion perfusion NN cord-014597-66vd2mdu 196 6 processes process NNS cord-014597-66vd2mdu 196 7 utilize utilize VBP cord-014597-66vd2mdu 196 8 hollow hollow JJ cord-014597-66vd2mdu 196 9 fiber fiber NN cord-014597-66vd2mdu 196 10 filters filter NNS cord-014597-66vd2mdu 196 11 . . . cord-014597-66vd2mdu 197 1 This this DT cord-014597-66vd2mdu 197 2 has have VBZ cord-014597-66vd2mdu 197 3 been be VBN cord-014597-66vd2mdu 197 4 observed observe VBN cord-014597-66vd2mdu 197 5 to to TO cord-014597-66vd2mdu 197 6 cause cause VB cord-014597-66vd2mdu 197 7 retention retention NN cord-014597-66vd2mdu 197 8 of of IN cord-014597-66vd2mdu 197 9 product product NN cord-014597-66vd2mdu 197 10 within within IN cord-014597-66vd2mdu 197 11 the the DT cord-014597-66vd2mdu 197 12 bioreactor bioreactor NN cord-014597-66vd2mdu 197 13 especially especially RB cord-014597-66vd2mdu 197 14 towards towards IN cord-014597-66vd2mdu 197 15 the the DT cord-014597-66vd2mdu 197 16 end end NN cord-014597-66vd2mdu 197 17 of of IN cord-014597-66vd2mdu 197 18 the the DT cord-014597-66vd2mdu 197 19 production production NN cord-014597-66vd2mdu 197 20 run run NN cord-014597-66vd2mdu 197 21 . . . cord-014597-66vd2mdu 198 1 Two two CD cord-014597-66vd2mdu 198 2 types type NNS cord-014597-66vd2mdu 198 3 of of IN cord-014597-66vd2mdu 198 4 experiments experiment NNS cord-014597-66vd2mdu 198 5 were be VBD cord-014597-66vd2mdu 198 6 conducted conduct VBN cord-014597-66vd2mdu 198 7 to to TO cord-014597-66vd2mdu 198 8 study study VB cord-014597-66vd2mdu 198 9 the the DT cord-014597-66vd2mdu 198 10 factors factor NNS cord-014597-66vd2mdu 198 11 contributing contribute VBG cord-014597-66vd2mdu 198 12 to to IN cord-014597-66vd2mdu 198 13 product product NN cord-014597-66vd2mdu 198 14 retention retention NN cord-014597-66vd2mdu 198 15 : : : cord-014597-66vd2mdu 199 1 -Spiking -Spiking NNP cord-014597-66vd2mdu 199 2 studies study NNS cord-014597-66vd2mdu 199 3 : : : cord-014597-66vd2mdu 200 1 -Role -Role : cord-014597-66vd2mdu 200 2 of of IN cord-014597-66vd2mdu 200 3 product product NN cord-014597-66vd2mdu 200 4 titer titer NN cord-014597-66vd2mdu 200 5 : : : cord-014597-66vd2mdu 200 6 product product NN cord-014597-66vd2mdu 200 7 was be VBD cord-014597-66vd2mdu 200 8 spiked spike VBN cord-014597-66vd2mdu 200 9 into into IN cord-014597-66vd2mdu 200 10 chemically chemically RB cord-014597-66vd2mdu 200 11 defined define VBN cord-014597-66vd2mdu 200 12 media medium NNS cord-014597-66vd2mdu 200 13 -Role -Role : cord-014597-66vd2mdu 200 14 of of IN cord-014597-66vd2mdu 200 15 different different JJ cord-014597-66vd2mdu 200 16 cell cell NN cord-014597-66vd2mdu 200 17 viability viability NN cord-014597-66vd2mdu 200 18 : : : cord-014597-66vd2mdu 200 19 different different JJ cord-014597-66vd2mdu 200 20 broths broth NNS cord-014597-66vd2mdu 200 21 with with IN cord-014597-66vd2mdu 200 22 varying vary VBG cord-014597-66vd2mdu 200 23 viability viability NN cord-014597-66vd2mdu 200 24 spiked spike VBN cord-014597-66vd2mdu 200 25 with with IN cord-014597-66vd2mdu 200 26 same same JJ cord-014597-66vd2mdu 200 27 product product NN cord-014597-66vd2mdu 200 28 titer titer NN cord-014597-66vd2mdu 200 29 -Evaluation -evaluation NN cord-014597-66vd2mdu 200 30 of of IN cord-014597-66vd2mdu 200 31 different different JJ cord-014597-66vd2mdu 200 32 hollow hollow JJ cord-014597-66vd2mdu 200 33 fiber fiber NN cord-014597-66vd2mdu 200 34 membrane membrane NN cord-014597-66vd2mdu 200 35 ( ( -LRB- cord-014597-66vd2mdu 200 36 M1 M1 NNP cord-014597-66vd2mdu 200 37 , , , cord-014597-66vd2mdu 200 38 M2 M2 NNP cord-014597-66vd2mdu 200 39 and and CC cord-014597-66vd2mdu 200 40 M3 M3 NNP cord-014597-66vd2mdu 200 41 ) ) -RRB- cord-014597-66vd2mdu 200 42 on on IN cord-014597-66vd2mdu 200 43 product product NN cord-014597-66vd2mdu 200 44 retention retention NN cord-014597-66vd2mdu 200 45 . . . cord-014597-66vd2mdu 201 1 From from IN cord-014597-66vd2mdu 201 2 spiking spike VBG cord-014597-66vd2mdu 201 3 studies study NNS cord-014597-66vd2mdu 201 4 , , , cord-014597-66vd2mdu 201 5 it -PRON- PRP cord-014597-66vd2mdu 201 6 was be VBD cord-014597-66vd2mdu 201 7 evident evident JJ cord-014597-66vd2mdu 201 8 that that IN cord-014597-66vd2mdu 201 9 cell cell NN cord-014597-66vd2mdu 201 10 debris debris NN cord-014597-66vd2mdu 201 11 and and CC cord-014597-66vd2mdu 201 12 poor poor JJ cord-014597-66vd2mdu 201 13 quality quality NN cord-014597-66vd2mdu 201 14 cell cell NN cord-014597-66vd2mdu 201 15 broth broth NN cord-014597-66vd2mdu 201 16 ( ( -LRB- cord-014597-66vd2mdu 201 17 lower low JJR cord-014597-66vd2mdu 201 18 viability viability NN cord-014597-66vd2mdu 201 19 ) ) -RRB- cord-014597-66vd2mdu 201 20 were be VBD cord-014597-66vd2mdu 201 21 the the DT cord-014597-66vd2mdu 201 22 major major JJ cord-014597-66vd2mdu 201 23 factors factor NNS cord-014597-66vd2mdu 201 24 contributing contribute VBG cord-014597-66vd2mdu 201 25 to to IN cord-014597-66vd2mdu 201 26 product product NN cord-014597-66vd2mdu 201 27 retention retention NN cord-014597-66vd2mdu 201 28 ( ( -LRB- cord-014597-66vd2mdu 201 29 Fig Fig NNP cord-014597-66vd2mdu 201 30 . . . cord-014597-66vd2mdu 201 31 1c 1c CD cord-014597-66vd2mdu 201 32 ) ) -RRB- cord-014597-66vd2mdu 201 33 . . . cord-014597-66vd2mdu 202 1 From from IN cord-014597-66vd2mdu 202 2 the the DT cord-014597-66vd2mdu 202 3 different different JJ cord-014597-66vd2mdu 202 4 membranes membrane NNS cord-014597-66vd2mdu 202 5 experiments experiment NNS cord-014597-66vd2mdu 202 6 , , , cord-014597-66vd2mdu 202 7 it -PRON- PRP cord-014597-66vd2mdu 202 8 was be VBD cord-014597-66vd2mdu 202 9 identified identify VBN cord-014597-66vd2mdu 202 10 that that IN cord-014597-66vd2mdu 202 11 at at IN cord-014597-66vd2mdu 202 12 Pilot pilot NN cord-014597-66vd2mdu 202 13 scale scale NN cord-014597-66vd2mdu 202 14 , , , cord-014597-66vd2mdu 202 15 M1 M1 NNP cord-014597-66vd2mdu 202 16 showed show VBD cord-014597-66vd2mdu 202 17 much much RB cord-014597-66vd2mdu 202 18 higher high JJR cord-014597-66vd2mdu 202 19 retention retention NN cord-014597-66vd2mdu 202 20 from from IN cord-014597-66vd2mdu 202 21 the the DT cord-014597-66vd2mdu 202 22 first first JJ cord-014597-66vd2mdu 202 23 perfusion perfusion NN cord-014597-66vd2mdu 202 24 cycle cycle NN cord-014597-66vd2mdu 202 25 itself -PRON- PRP cord-014597-66vd2mdu 203 1 and and CC cord-014597-66vd2mdu 203 2 it -PRON- PRP cord-014597-66vd2mdu 203 3 increased increase VBD cord-014597-66vd2mdu 203 4 to to IN cord-014597-66vd2mdu 203 5 more more JJR cord-014597-66vd2mdu 203 6 than than IN cord-014597-66vd2mdu 203 7 75 75 CD cord-014597-66vd2mdu 203 8 % % NN cord-014597-66vd2mdu 203 9 towards towards IN cord-014597-66vd2mdu 203 10 the the DT cord-014597-66vd2mdu 203 11 end end NN cord-014597-66vd2mdu 203 12 of of IN cord-014597-66vd2mdu 203 13 the the DT cord-014597-66vd2mdu 203 14 batch batch NN cord-014597-66vd2mdu 203 15 . . . cord-014597-66vd2mdu 204 1 However however RB cord-014597-66vd2mdu 204 2 , , , cord-014597-66vd2mdu 204 3 with with IN cord-014597-66vd2mdu 204 4 M2 M2 NNP cord-014597-66vd2mdu 204 5 membrane membrane NN cord-014597-66vd2mdu 204 6 , , , cord-014597-66vd2mdu 204 7 product product NN cord-014597-66vd2mdu 204 8 retention retention NN cord-014597-66vd2mdu 204 9 started start VBD cord-014597-66vd2mdu 204 10 only only RB cord-014597-66vd2mdu 204 11 late late RB cord-014597-66vd2mdu 204 12 ( ( -LRB- cord-014597-66vd2mdu 204 13 after after IN cord-014597-66vd2mdu 204 14 50 50 CD cord-014597-66vd2mdu 204 15 % % NN cord-014597-66vd2mdu 204 16 of of IN cord-014597-66vd2mdu 204 17 batch batch NN cord-014597-66vd2mdu 204 18 duration duration NN cord-014597-66vd2mdu 204 19 ) ) -RRB- cord-014597-66vd2mdu 204 20 and and CC cord-014597-66vd2mdu 204 21 it -PRON- PRP cord-014597-66vd2mdu 204 22 remained remain VBD cord-014597-66vd2mdu 204 23 low low JJ cord-014597-66vd2mdu 204 24 ( ( -LRB- cord-014597-66vd2mdu 204 25 ~20 ~20 NFP cord-014597-66vd2mdu 204 26 - - : cord-014597-66vd2mdu 204 27 40 40 CD cord-014597-66vd2mdu 204 28 % % NN cord-014597-66vd2mdu 204 29 ) ) -RRB- cord-014597-66vd2mdu 204 30 . . . cord-014597-66vd2mdu 205 1 On on IN cord-014597-66vd2mdu 205 2 the the DT cord-014597-66vd2mdu 205 3 contrary contrary NN cord-014597-66vd2mdu 205 4 , , , cord-014597-66vd2mdu 205 5 this this DT cord-014597-66vd2mdu 205 6 difference difference NN cord-014597-66vd2mdu 205 7 was be VBD cord-014597-66vd2mdu 205 8 not not RB cord-014597-66vd2mdu 205 9 observed observe VBN cord-014597-66vd2mdu 205 10 at at IN cord-014597-66vd2mdu 205 11 1L 1l CD cord-014597-66vd2mdu 205 12 scale scale NN cord-014597-66vd2mdu 205 13 due due IN cord-014597-66vd2mdu 205 14 to to IN cord-014597-66vd2mdu 205 15 the the DT cord-014597-66vd2mdu 205 16 usage usage NN cord-014597-66vd2mdu 205 17 of of IN cord-014597-66vd2mdu 205 18 membranes membrane NNS cord-014597-66vd2mdu 205 19 with with IN cord-014597-66vd2mdu 205 20 larger large JJR cord-014597-66vd2mdu 205 21 filter filter NN cord-014597-66vd2mdu 205 22 area area NN cord-014597-66vd2mdu 205 23 ( ( -LRB- cord-014597-66vd2mdu 205 24 2 2 CD cord-014597-66vd2mdu 205 25 - - SYM cord-014597-66vd2mdu 205 26 3 3 CD cord-014597-66vd2mdu 205 27 folds fold NNS cord-014597-66vd2mdu 205 28 higher higher RBR cord-014597-66vd2mdu 205 29 compared compare VBN cord-014597-66vd2mdu 205 30 to to IN cord-014597-66vd2mdu 205 31 pilot pilot NN cord-014597-66vd2mdu 205 32 scale scale NN cord-014597-66vd2mdu 205 33 ) ) -RRB- cord-014597-66vd2mdu 205 34 . . . cord-014597-66vd2mdu 206 1 When when WRB cord-014597-66vd2mdu 206 2 the the DT cord-014597-66vd2mdu 206 3 filter filter NN cord-014597-66vd2mdu 206 4 area area NN cord-014597-66vd2mdu 206 5 per per IN cord-014597-66vd2mdu 206 6 unit unit NN cord-014597-66vd2mdu 206 7 volume volume NN cord-014597-66vd2mdu 206 8 of of IN cord-014597-66vd2mdu 206 9 perfusate perfusate NN cord-014597-66vd2mdu 206 10 was be VBD cord-014597-66vd2mdu 206 11 decreased decrease VBN cord-014597-66vd2mdu 206 12 by by IN cord-014597-66vd2mdu 206 13 half half NN cord-014597-66vd2mdu 206 14 ( ( -LRB- cord-014597-66vd2mdu 206 15 M2_Batch M2_Batch NNP cord-014597-66vd2mdu 206 16 4 4 CD cord-014597-66vd2mdu 206 17 ) ) -RRB- cord-014597-66vd2mdu 206 18 for for IN cord-014597-66vd2mdu 206 19 the the DT cord-014597-66vd2mdu 206 20 pilot pilot NN cord-014597-66vd2mdu 206 21 scale scale NN cord-014597-66vd2mdu 206 22 , , , cord-014597-66vd2mdu 206 23 even even RB cord-014597-66vd2mdu 206 24 M2 M2 NNP cord-014597-66vd2mdu 206 25 showed show VBD cord-014597-66vd2mdu 206 26 retention retention NN cord-014597-66vd2mdu 206 27 profile profile NN cord-014597-66vd2mdu 206 28 similar similar JJ cord-014597-66vd2mdu 206 29 to to IN cord-014597-66vd2mdu 206 30 M1 M1 NNP cord-014597-66vd2mdu 206 31 ( ( -LRB- cord-014597-66vd2mdu 206 32 Fig Fig NNP cord-014597-66vd2mdu 206 33 . . . cord-014597-66vd2mdu 206 34 1d 1d CD cord-014597-66vd2mdu 206 35 ) ) -RRB- cord-014597-66vd2mdu 206 36 . . . cord-014597-66vd2mdu 207 1 We -PRON- PRP cord-014597-66vd2mdu 207 2 presented present VBD cord-014597-66vd2mdu 207 3 data datum NNS cord-014597-66vd2mdu 207 4 to to TO cord-014597-66vd2mdu 207 5 show show VB cord-014597-66vd2mdu 207 6 that that IN cord-014597-66vd2mdu 207 7 perfusion perfusion NN cord-014597-66vd2mdu 207 8 process process NN cord-014597-66vd2mdu 207 9 has have VBZ cord-014597-66vd2mdu 207 10 5-fold 5-fold CD cord-014597-66vd2mdu 207 11 increase increase NN cord-014597-66vd2mdu 207 12 in in IN cord-014597-66vd2mdu 207 13 product product NN cord-014597-66vd2mdu 207 14 yield yield NN cord-014597-66vd2mdu 207 15 on on IN cord-014597-66vd2mdu 207 16 a a DT cord-014597-66vd2mdu 207 17 per per IN cord-014597-66vd2mdu 207 18 - - HYPH cord-014597-66vd2mdu 207 19 batch batch NN cord-014597-66vd2mdu 207 20 basis basis NN cord-014597-66vd2mdu 207 21 and and CC cord-014597-66vd2mdu 207 22 a a DT cord-014597-66vd2mdu 207 23 3-fold 3-fold CD cord-014597-66vd2mdu 207 24 increase increase NN cord-014597-66vd2mdu 207 25 when when WRB cord-014597-66vd2mdu 207 26 facility facility NN cord-014597-66vd2mdu 207 27 throughput throughput NN cord-014597-66vd2mdu 207 28 is be VBZ cord-014597-66vd2mdu 207 29 considered consider VBN cord-014597-66vd2mdu 207 30 . . . cord-014597-66vd2mdu 208 1 Product product NN cord-014597-66vd2mdu 208 2 retention retention NN cord-014597-66vd2mdu 208 3 is be VBZ cord-014597-66vd2mdu 208 4 a a DT cord-014597-66vd2mdu 208 5 technical technical JJ cord-014597-66vd2mdu 208 6 challenge challenge NN cord-014597-66vd2mdu 208 7 that that WDT cord-014597-66vd2mdu 208 8 requires require VBZ cord-014597-66vd2mdu 208 9 optimization optimization NN cord-014597-66vd2mdu 208 10 ( ( -LRB- cord-014597-66vd2mdu 208 11 perfusion perfusion NN cord-014597-66vd2mdu 208 12 rates rate NNS cord-014597-66vd2mdu 208 13 and and CC cord-014597-66vd2mdu 208 14 filter filter NN cord-014597-66vd2mdu 208 15 membrane membrane NN cord-014597-66vd2mdu 208 16 types type NNS cord-014597-66vd2mdu 208 17 ) ) -RRB- cord-014597-66vd2mdu 208 18 . . . cord-014597-66vd2mdu 209 1 We -PRON- PRP cord-014597-66vd2mdu 209 2 believe believe VBP cord-014597-66vd2mdu 209 3 it -PRON- PRP cord-014597-66vd2mdu 209 4 is be VBZ cord-014597-66vd2mdu 209 5 imperative imperative JJ cord-014597-66vd2mdu 209 6 that that IN cord-014597-66vd2mdu 209 7 labs lab NNS cord-014597-66vd2mdu 209 8 that that WDT cord-014597-66vd2mdu 209 9 develop develop VBP cord-014597-66vd2mdu 209 10 processes process NNS cord-014597-66vd2mdu 209 11 for for IN cord-014597-66vd2mdu 209 12 biologics biologic NNS cord-014597-66vd2mdu 209 13 can can MD cord-014597-66vd2mdu 209 14 now now RB cord-014597-66vd2mdu 209 15 consider consider VB cord-014597-66vd2mdu 209 16 both both DT cord-014597-66vd2mdu 209 17 perfusion perfusion NN cord-014597-66vd2mdu 209 18 and and CC cord-014597-66vd2mdu 209 19 fedbatch fedbatch NN cord-014597-66vd2mdu 209 20 based base VBN cord-014597-66vd2mdu 209 21 processes process NNS cord-014597-66vd2mdu 209 22 as as IN cord-014597-66vd2mdu 209 23 both both PDT cord-014597-66vd2mdu 209 24 these these DT cord-014597-66vd2mdu 209 25 technologies technology NNS cord-014597-66vd2mdu 209 26 can can MD cord-014597-66vd2mdu 209 27 now now RB cord-014597-66vd2mdu 209 28 closely closely RB cord-014597-66vd2mdu 209 29 compete compete VB cord-014597-66vd2mdu 209 30 with with IN cord-014597-66vd2mdu 209 31 each each DT cord-014597-66vd2mdu 209 32 other other JJ cord-014597-66vd2mdu 209 33 . . . cord-014597-66vd2mdu 210 1 The the DT cord-014597-66vd2mdu 210 2 choice choice NN cord-014597-66vd2mdu 210 3 of of IN cord-014597-66vd2mdu 210 4 the the DT cord-014597-66vd2mdu 210 5 process process NN cord-014597-66vd2mdu 210 6 format format NN cord-014597-66vd2mdu 210 7 going go VBG cord-014597-66vd2mdu 210 8 forward forward RB cord-014597-66vd2mdu 210 9 should should MD cord-014597-66vd2mdu 210 10 now now RB cord-014597-66vd2mdu 210 11 solely solely RB cord-014597-66vd2mdu 210 12 be be VB cord-014597-66vd2mdu 210 13 dependent dependent JJ cord-014597-66vd2mdu 210 14 on on IN cord-014597-66vd2mdu 210 15 the the DT cord-014597-66vd2mdu 210 16 requirement requirement NN cord-014597-66vd2mdu 210 17 for for IN cord-014597-66vd2mdu 210 18 the the DT cord-014597-66vd2mdu 210 19 biologic biologic NN cord-014597-66vd2mdu 210 20 rather rather RB cord-014597-66vd2mdu 210 21 than than IN cord-014597-66vd2mdu 210 22 the the DT cord-014597-66vd2mdu 210 23 earlier early JJR cord-014597-66vd2mdu 210 24 perception perception NN cord-014597-66vd2mdu 210 25 that that IN cord-014597-66vd2mdu 210 26 fed fed NN cord-014597-66vd2mdu 210 27 - - HYPH cord-014597-66vd2mdu 210 28 batch batch NN cord-014597-66vd2mdu 210 29 is be VBZ cord-014597-66vd2mdu 210 30 the the DT cord-014597-66vd2mdu 210 31 preferred preferred JJ cord-014597-66vd2mdu 210 32 choice choice NN cord-014597-66vd2mdu 210 33 because because IN cord-014597-66vd2mdu 210 34 of of IN cord-014597-66vd2mdu 210 35 its -PRON- PRP$ cord-014597-66vd2mdu 210 36 simplicity simplicity NN cord-014597-66vd2mdu 210 37 . . . cord-014597-66vd2mdu 211 1 Background background NN cord-014597-66vd2mdu 211 2 Chinese chinese JJ cord-014597-66vd2mdu 211 3 hamster hamster NN cord-014597-66vd2mdu 211 4 ovary ovary NN cord-014597-66vd2mdu 212 1 ( ( -LRB- cord-014597-66vd2mdu 212 2 CHO CHO NNP cord-014597-66vd2mdu 212 3 ) ) -RRB- cord-014597-66vd2mdu 212 4 cell cell NN cord-014597-66vd2mdu 212 5 culture culture NN cord-014597-66vd2mdu 212 6 has have VBZ cord-014597-66vd2mdu 212 7 been be VBN cord-014597-66vd2mdu 212 8 widely widely RB cord-014597-66vd2mdu 212 9 used use VBN cord-014597-66vd2mdu 212 10 for for IN cord-014597-66vd2mdu 212 11 production production NN cord-014597-66vd2mdu 212 12 of of IN cord-014597-66vd2mdu 212 13 monoclonal monoclonal JJ cord-014597-66vd2mdu 212 14 antibodies antibody NNS cord-014597-66vd2mdu 212 15 in in IN cord-014597-66vd2mdu 212 16 the the DT cord-014597-66vd2mdu 212 17 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 212 18 industry industry NN cord-014597-66vd2mdu 212 19 . . . cord-014597-66vd2mdu 213 1 Previous previous JJ cord-014597-66vd2mdu 213 2 studies study NNS cord-014597-66vd2mdu 213 3 have have VBP cord-014597-66vd2mdu 213 4 shown show VBN cord-014597-66vd2mdu 213 5 that that IN cord-014597-66vd2mdu 213 6 the the DT cord-014597-66vd2mdu 213 7 cell cell NN cord-014597-66vd2mdu 213 8 specific specific JJ cord-014597-66vd2mdu 213 9 productivity productivity NN cord-014597-66vd2mdu 213 10 in in IN cord-014597-66vd2mdu 213 11 CHO CHO NNP cord-014597-66vd2mdu 213 12 cells cell NNS cord-014597-66vd2mdu 213 13 can can MD cord-014597-66vd2mdu 213 14 be be VB cord-014597-66vd2mdu 213 15 increased increase VBN cord-014597-66vd2mdu 213 16 by by IN cord-014597-66vd2mdu 213 17 glucose glucose NN cord-014597-66vd2mdu 213 18 limitation limitation NN cord-014597-66vd2mdu 213 19 [ [ -LRB- cord-014597-66vd2mdu 213 20 1 1 CD cord-014597-66vd2mdu 213 21 ] ] -RRB- cord-014597-66vd2mdu 213 22 . . . cord-014597-66vd2mdu 214 1 Introducing introduce VBG cord-014597-66vd2mdu 214 2 a a DT cord-014597-66vd2mdu 214 3 productivity productivity NN cord-014597-66vd2mdu 214 4 enhancing enhance VBG cord-014597-66vd2mdu 214 5 effect effect NN cord-014597-66vd2mdu 214 6 it -PRON- PRP cord-014597-66vd2mdu 214 7 is be VBZ cord-014597-66vd2mdu 214 8 possible possible JJ cord-014597-66vd2mdu 214 9 that that IN cord-014597-66vd2mdu 214 10 this this DT cord-014597-66vd2mdu 214 11 also also RB cord-014597-66vd2mdu 214 12 affects affect VBZ cord-014597-66vd2mdu 214 13 the the DT cord-014597-66vd2mdu 214 14 quality quality NN cord-014597-66vd2mdu 214 15 of of IN cord-014597-66vd2mdu 214 16 the the DT cord-014597-66vd2mdu 214 17 product product NN cord-014597-66vd2mdu 214 18 such such JJ cord-014597-66vd2mdu 214 19 as as IN cord-014597-66vd2mdu 214 20 glycosylation glycosylation NN cord-014597-66vd2mdu 214 21 or or CC cord-014597-66vd2mdu 214 22 other other JJ cord-014597-66vd2mdu 214 23 posttranslational posttranslational JJ cord-014597-66vd2mdu 214 24 modifications modification NNS cord-014597-66vd2mdu 214 25 . . . cord-014597-66vd2mdu 215 1 In in IN cord-014597-66vd2mdu 215 2 this this DT cord-014597-66vd2mdu 215 3 work work NN cord-014597-66vd2mdu 215 4 , , , cord-014597-66vd2mdu 215 5 we -PRON- PRP cord-014597-66vd2mdu 215 6 are be VBP cord-014597-66vd2mdu 215 7 focusing focus VBG cord-014597-66vd2mdu 215 8 on on IN cord-014597-66vd2mdu 215 9 the the DT cord-014597-66vd2mdu 215 10 impact impact NN cord-014597-66vd2mdu 215 11 of of IN cord-014597-66vd2mdu 215 12 glucose glucose NN cord-014597-66vd2mdu 215 13 limitation limitation NN cord-014597-66vd2mdu 215 14 and and CC cord-014597-66vd2mdu 215 15 increased increase VBN cord-014597-66vd2mdu 215 16 productivity productivity NN cord-014597-66vd2mdu 215 17 on on IN cord-014597-66vd2mdu 215 18 the the DT cord-014597-66vd2mdu 215 19 product product NN cord-014597-66vd2mdu 215 20 quality quality NN cord-014597-66vd2mdu 215 21 of of IN cord-014597-66vd2mdu 215 22 a a DT cord-014597-66vd2mdu 215 23 monoclonal monoclonal JJ cord-014597-66vd2mdu 215 24 antibody antibody NN cord-014597-66vd2mdu 215 25 produced produce VBN cord-014597-66vd2mdu 215 26 in in IN cord-014597-66vd2mdu 215 27 a a DT cord-014597-66vd2mdu 215 28 fed feed VBN cord-014597-66vd2mdu 215 29 - - HYPH cord-014597-66vd2mdu 215 30 batch batch NN cord-014597-66vd2mdu 215 31 cultivation cultivation NN cord-014597-66vd2mdu 215 32 of of IN cord-014597-66vd2mdu 215 33 CHO CHO NNP cord-014597-66vd2mdu 215 34 cells cell NNS cord-014597-66vd2mdu 215 35 . . . cord-014597-66vd2mdu 216 1 Materials material NNS cord-014597-66vd2mdu 216 2 and and CC cord-014597-66vd2mdu 216 3 methods method NNS cord-014597-66vd2mdu 216 4 CHO CHO NNP cord-014597-66vd2mdu 216 5 cells cell NNS cord-014597-66vd2mdu 216 6 were be VBD cord-014597-66vd2mdu 216 7 cultivated cultivate VBN cord-014597-66vd2mdu 216 8 both both DT cord-014597-66vd2mdu 216 9 under under IN cord-014597-66vd2mdu 216 10 limiting limit VBG cord-014597-66vd2mdu 216 11 and and CC cord-014597-66vd2mdu 216 12 non non JJ cord-014597-66vd2mdu 216 13 - - JJ cord-014597-66vd2mdu 216 14 limiting limit VBG cord-014597-66vd2mdu 216 15 nutrient nutrient NN cord-014597-66vd2mdu 216 16 conditions condition NNS cord-014597-66vd2mdu 216 17 in in IN cord-014597-66vd2mdu 216 18 fed fed NNP cord-014597-66vd2mdu 216 19 - - HYPH cord-014597-66vd2mdu 216 20 batch batch NN cord-014597-66vd2mdu 216 21 . . . cord-014597-66vd2mdu 217 1 For for IN cord-014597-66vd2mdu 217 2 fed fed JJ cord-014597-66vd2mdu 217 3 - - HYPH cord-014597-66vd2mdu 217 4 batch batch NN cord-014597-66vd2mdu 217 5 cultivation cultivation NN cord-014597-66vd2mdu 217 6 the the DT cord-014597-66vd2mdu 217 7 reduced reduce VBN cord-014597-66vd2mdu 217 8 range range NN cord-014597-66vd2mdu 217 9 for for IN cord-014597-66vd2mdu 217 10 glucose glucose NN cord-014597-66vd2mdu 217 11 concentration concentration NN cord-014597-66vd2mdu 217 12 was be VBD cord-014597-66vd2mdu 217 13 chosen choose VBN cord-014597-66vd2mdu 217 14 between between IN cord-014597-66vd2mdu 217 15 0.2 0.2 CD cord-014597-66vd2mdu 217 16 and and CC cord-014597-66vd2mdu 217 17 0.5 0.5 CD cord-014597-66vd2mdu 217 18 g/ g/ NNP cord-014597-66vd2mdu 217 19 L. L. NNP cord-014597-66vd2mdu 217 20 Reference Reference NNP cord-014597-66vd2mdu 217 21 cultivation cultivation NN cord-014597-66vd2mdu 217 22 was be VBD cord-014597-66vd2mdu 217 23 performed perform VBN cord-014597-66vd2mdu 217 24 between between IN cord-014597-66vd2mdu 217 25 1.5 1.5 CD cord-014597-66vd2mdu 217 26 and and CC cord-014597-66vd2mdu 217 27 3.0 3.0 CD cord-014597-66vd2mdu 217 28 g g NN cord-014597-66vd2mdu 217 29 / / SYM cord-014597-66vd2mdu 217 30 L. L. NNP cord-014597-66vd2mdu 218 1 Both both DT cord-014597-66vd2mdu 218 2 cultures culture NNS cord-014597-66vd2mdu 218 3 were be VBD cord-014597-66vd2mdu 218 4 fed feed VBN cord-014597-66vd2mdu 218 5 with with IN cord-014597-66vd2mdu 218 6 similar similar JJ cord-014597-66vd2mdu 218 7 volumes volume NNS cord-014597-66vd2mdu 218 8 of of IN cord-014597-66vd2mdu 218 9 a a DT cord-014597-66vd2mdu 218 10 complex complex JJ cord-014597-66vd2mdu 218 11 nutrient nutrient NN cord-014597-66vd2mdu 218 12 supplement supplement NN cord-014597-66vd2mdu 218 13 . . . cord-014597-66vd2mdu 219 1 All all DT cord-014597-66vd2mdu 219 2 cultivations cultivation NNS cord-014597-66vd2mdu 219 3 were be VBD cord-014597-66vd2mdu 219 4 performed perform VBN cord-014597-66vd2mdu 219 5 in in IN cord-014597-66vd2mdu 219 6 chemically chemically RB cord-014597-66vd2mdu 219 7 - - HYPH cord-014597-66vd2mdu 219 8 defined define VBN cord-014597-66vd2mdu 219 9 , , , cord-014597-66vd2mdu 219 10 animalcomponent animalcomponent JJ cord-014597-66vd2mdu 219 11 free free JJ cord-014597-66vd2mdu 219 12 CHO CHO NNP cord-014597-66vd2mdu 219 13 growth growth NN cord-014597-66vd2mdu 219 14 media medium NNS cord-014597-66vd2mdu 219 15 ( ( -LRB- cord-014597-66vd2mdu 219 16 Xell Xell NNP cord-014597-66vd2mdu 219 17 AG AG NNP cord-014597-66vd2mdu 219 18 ) ) -RRB- cord-014597-66vd2mdu 219 19 . . . cord-014597-66vd2mdu 220 1 Viable viable JJ cord-014597-66vd2mdu 220 2 cell cell NN cord-014597-66vd2mdu 220 3 density density NN cord-014597-66vd2mdu 220 4 and and CC cord-014597-66vd2mdu 220 5 viability viability NN cord-014597-66vd2mdu 220 6 were be VBD cord-014597-66vd2mdu 220 7 determined determine VBN cord-014597-66vd2mdu 220 8 using use VBG cord-014597-66vd2mdu 220 9 the the DT cord-014597-66vd2mdu 220 10 automated automate VBN cord-014597-66vd2mdu 220 11 cell cell NN cord-014597-66vd2mdu 220 12 counting counting NN cord-014597-66vd2mdu 220 13 system system NN cord-014597-66vd2mdu 220 14 CEDEX CEDEX NNP cord-014597-66vd2mdu 220 15 ( ( -LRB- cord-014597-66vd2mdu 220 16 Roche Roche NNP cord-014597-66vd2mdu 220 17 Diagnostics Diagnostics NNP cord-014597-66vd2mdu 220 18 ) ) -RRB- cord-014597-66vd2mdu 220 19 , , , cord-014597-66vd2mdu 220 20 glucose glucose NN cord-014597-66vd2mdu 220 21 and and CC cord-014597-66vd2mdu 220 22 lactate lactate NN cord-014597-66vd2mdu 220 23 concentrations concentration NNS cord-014597-66vd2mdu 220 24 were be VBD cord-014597-66vd2mdu 220 25 detected detect VBN cord-014597-66vd2mdu 220 26 via via IN cord-014597-66vd2mdu 220 27 YSI YSI NNP cord-014597-66vd2mdu 220 28 ( ( -LRB- cord-014597-66vd2mdu 220 29 YSI YSI NNP cord-014597-66vd2mdu 220 30 life life NN cord-014597-66vd2mdu 220 31 sciences science NNS cord-014597-66vd2mdu 220 32 ) ) -RRB- cord-014597-66vd2mdu 220 33 . . . cord-014597-66vd2mdu 221 1 Amino amino NN cord-014597-66vd2mdu 221 2 acid acid NN cord-014597-66vd2mdu 221 3 were be VBD cord-014597-66vd2mdu 221 4 quantified quantify VBN cord-014597-66vd2mdu 221 5 using use VBG cord-014597-66vd2mdu 221 6 HPLC HPLC NNP cord-014597-66vd2mdu 221 7 - - HYPH cord-014597-66vd2mdu 221 8 FLD FLD NNP cord-014597-66vd2mdu 221 9 , , , cord-014597-66vd2mdu 221 10 vitamins vitamin NNS cord-014597-66vd2mdu 221 11 were be VBD cord-014597-66vd2mdu 221 12 quantified quantify VBN cord-014597-66vd2mdu 221 13 using use VBG cord-014597-66vd2mdu 221 14 reversed reversed JJ cord-014597-66vd2mdu 221 15 phase phase NN cord-014597-66vd2mdu 221 16 chromatography chromatography NN cord-014597-66vd2mdu 221 17 coupled couple VBN cord-014597-66vd2mdu 221 18 to to IN cord-014597-66vd2mdu 221 19 a a DT cord-014597-66vd2mdu 221 20 triple triple JJ cord-014597-66vd2mdu 221 21 quadrupol quadrupol NN cord-014597-66vd2mdu 221 22 mass mass NN cord-014597-66vd2mdu 221 23 spectrometer spectrometer NN cord-014597-66vd2mdu 221 24 ( ( -LRB- cord-014597-66vd2mdu 221 25 Varian Varian NNP cord-014597-66vd2mdu 221 26 320 320 CD cord-014597-66vd2mdu 221 27 , , , cord-014597-66vd2mdu 221 28 selected select VBN cord-014597-66vd2mdu 221 29 reaction reaction NN cord-014597-66vd2mdu 221 30 monitoring monitoring NN cord-014597-66vd2mdu 221 31 ) ) -RRB- cord-014597-66vd2mdu 221 32 . . . cord-014597-66vd2mdu 222 1 Amounts amount NNS cord-014597-66vd2mdu 222 2 of of IN cord-014597-66vd2mdu 222 3 IgG1 IgG1 NNP cord-014597-66vd2mdu 222 4 were be VBD cord-014597-66vd2mdu 222 5 quantified quantify VBN cord-014597-66vd2mdu 222 6 via via IN cord-014597-66vd2mdu 222 7 Protein Protein NNP cord-014597-66vd2mdu 222 8 A a DT cord-014597-66vd2mdu 222 9 HPLC HPLC NNP cord-014597-66vd2mdu 222 10 , , , cord-014597-66vd2mdu 222 11 mAb mAb NNS cord-014597-66vd2mdu 222 12 purified purify VBN cord-014597-66vd2mdu 222 13 from from IN cord-014597-66vd2mdu 222 14 another another DT cord-014597-66vd2mdu 222 15 CHO CHO NNP cord-014597-66vd2mdu 222 16 cell cell NN cord-014597-66vd2mdu 222 17 clone clone NN cord-014597-66vd2mdu 222 18 was be VBD cord-014597-66vd2mdu 222 19 used use VBN cord-014597-66vd2mdu 222 20 as as IN cord-014597-66vd2mdu 222 21 a a DT cord-014597-66vd2mdu 222 22 standard standard NN cord-014597-66vd2mdu 222 23 . . . cord-014597-66vd2mdu 223 1 The the DT cord-014597-66vd2mdu 223 2 analysis analysis NN cord-014597-66vd2mdu 223 3 of of IN cord-014597-66vd2mdu 223 4 product product NN cord-014597-66vd2mdu 223 5 quality quality NN cord-014597-66vd2mdu 223 6 was be VBD cord-014597-66vd2mdu 223 7 performed perform VBN cord-014597-66vd2mdu 223 8 by by IN cord-014597-66vd2mdu 223 9 intact intact JJ cord-014597-66vd2mdu 223 10 mass mass NN cord-014597-66vd2mdu 223 11 analysis analysis NN cord-014597-66vd2mdu 223 12 using use VBG cord-014597-66vd2mdu 223 13 reversed reversed JJ cord-014597-66vd2mdu 223 14 phase phase NN cord-014597-66vd2mdu 223 15 chromatography chromatography NN cord-014597-66vd2mdu 223 16 coupled couple VBN cord-014597-66vd2mdu 223 17 to to IN cord-014597-66vd2mdu 223 18 a a DT cord-014597-66vd2mdu 223 19 microOTOF microotof NN cord-014597-66vd2mdu 223 20 - - HYPH cord-014597-66vd2mdu 223 21 Q Q NNP cord-014597-66vd2mdu 223 22 II II NNP cord-014597-66vd2mdu 223 23 mass mass NN cord-014597-66vd2mdu 223 24 spectrometer spectrometer NN cord-014597-66vd2mdu 223 25 ( ( -LRB- cord-014597-66vd2mdu 223 26 Bruker Bruker NNP cord-014597-66vd2mdu 223 27 Daltonik Daltonik NNP cord-014597-66vd2mdu 223 28 ) ) -RRB- cord-014597-66vd2mdu 223 29 . . . cord-014597-66vd2mdu 224 1 The the DT cord-014597-66vd2mdu 224 2 CHO CHO NNP cord-014597-66vd2mdu 224 3 cell cell NN cord-014597-66vd2mdu 224 4 culture culture NN cord-014597-66vd2mdu 224 5 cultivated cultivate VBN cord-014597-66vd2mdu 224 6 under under IN cord-014597-66vd2mdu 224 7 low low JJ cord-014597-66vd2mdu 224 8 nutrient nutrient NN cord-014597-66vd2mdu 224 9 conditions condition NNS cord-014597-66vd2mdu 224 10 reached reach VBD cord-014597-66vd2mdu 224 11 a a DT cord-014597-66vd2mdu 224 12 54 54 CD cord-014597-66vd2mdu 224 13 % % NN cord-014597-66vd2mdu 224 14 higher high JJR cord-014597-66vd2mdu 224 15 viable viable JJ cord-014597-66vd2mdu 224 16 cell cell NN cord-014597-66vd2mdu 224 17 density density NN cord-014597-66vd2mdu 224 18 than than IN cord-014597-66vd2mdu 224 19 the the DT cord-014597-66vd2mdu 224 20 reference reference NN cord-014597-66vd2mdu 224 21 culture culture NN cord-014597-66vd2mdu 224 22 ( ( -LRB- cord-014597-66vd2mdu 224 23 Fig Fig NNP cord-014597-66vd2mdu 224 24 . . . cord-014597-66vd2mdu 224 25 1a 1a CD cord-014597-66vd2mdu 224 26 ) ) -RRB- cord-014597-66vd2mdu 224 27 . . . cord-014597-66vd2mdu 225 1 The the DT cord-014597-66vd2mdu 225 2 product product NN cord-014597-66vd2mdu 225 3 titer titer NN cord-014597-66vd2mdu 225 4 was be VBD cord-014597-66vd2mdu 225 5 even even RB cord-014597-66vd2mdu 225 6 increased increase VBN cord-014597-66vd2mdu 225 7 by by IN cord-014597-66vd2mdu 225 8 109 109 CD cord-014597-66vd2mdu 225 9 % % NN cord-014597-66vd2mdu 225 10 ( ( -LRB- cord-014597-66vd2mdu 225 11 Fig Fig NNP cord-014597-66vd2mdu 225 12 . . . cord-014597-66vd2mdu 225 13 1b 1b CD cord-014597-66vd2mdu 225 14 ) ) -RRB- cord-014597-66vd2mdu 225 15 . . . cord-014597-66vd2mdu 226 1 The the DT cord-014597-66vd2mdu 226 2 spent spend VBN cord-014597-66vd2mdu 226 3 media medium NNS cord-014597-66vd2mdu 226 4 analysis analysis NN cord-014597-66vd2mdu 226 5 shows show VBZ cord-014597-66vd2mdu 226 6 that that IN cord-014597-66vd2mdu 226 7 some some DT cord-014597-66vd2mdu 226 8 amino amino JJ cord-014597-66vd2mdu 226 9 acids acid NNS cord-014597-66vd2mdu 226 10 and and CC cord-014597-66vd2mdu 226 11 vitamins vitamin NNS cord-014597-66vd2mdu 226 12 were be VBD cord-014597-66vd2mdu 226 13 present present JJ cord-014597-66vd2mdu 226 14 at at IN cord-014597-66vd2mdu 226 15 presumably presumably RB cord-014597-66vd2mdu 226 16 limiting limit VBG cord-014597-66vd2mdu 226 17 concentrations concentration NNS cord-014597-66vd2mdu 226 18 after after IN cord-014597-66vd2mdu 226 19 day day NN cord-014597-66vd2mdu 226 20 5/6 5/6 CD cord-014597-66vd2mdu 226 21 , , , cord-014597-66vd2mdu 226 22 mostly mostly RB cord-014597-66vd2mdu 226 23 in in IN cord-014597-66vd2mdu 226 24 the the DT cord-014597-66vd2mdu 226 25 low low JJ cord-014597-66vd2mdu 226 26 nutrient nutrient NN cord-014597-66vd2mdu 226 27 level level NN cord-014597-66vd2mdu 226 28 culture culture NN cord-014597-66vd2mdu 226 29 ( ( -LRB- cord-014597-66vd2mdu 226 30 down down IN cord-014597-66vd2mdu 226 31 to to IN cord-014597-66vd2mdu 226 32 40 40 CD cord-014597-66vd2mdu 226 33 to to TO cord-014597-66vd2mdu 226 34 190 190 CD cord-014597-66vd2mdu 226 35 μM μm NN cord-014597-66vd2mdu 226 36 for for IN cord-014597-66vd2mdu 226 37 TYR TYR NNP cord-014597-66vd2mdu 226 38 , , , cord-014597-66vd2mdu 226 39 GLN GLN NNP cord-014597-66vd2mdu 226 40 , , , cord-014597-66vd2mdu 226 41 ARG ARG NNP cord-014597-66vd2mdu 226 42 , , , cord-014597-66vd2mdu 226 43 and and CC cord-014597-66vd2mdu 226 44 ASN ASN NNP cord-014597-66vd2mdu 226 45 , , , cord-014597-66vd2mdu 226 46 below below IN cord-014597-66vd2mdu 226 47 1 1 CD cord-014597-66vd2mdu 226 48 μM μm NN cord-014597-66vd2mdu 226 49 for for IN cord-014597-66vd2mdu 226 50 pyridoxine pyridoxine NN cord-014597-66vd2mdu 226 51 , , , cord-014597-66vd2mdu 226 52 data datum NNS cord-014597-66vd2mdu 226 53 not not RB cord-014597-66vd2mdu 226 54 shown show VBN cord-014597-66vd2mdu 226 55 ) ) -RRB- cord-014597-66vd2mdu 226 56 . . . cord-014597-66vd2mdu 227 1 The the DT cord-014597-66vd2mdu 227 2 product product NN cord-014597-66vd2mdu 227 3 quality quality NN cord-014597-66vd2mdu 227 4 showed show VBD cord-014597-66vd2mdu 227 5 significant significant JJ cord-014597-66vd2mdu 227 6 changes change NNS cord-014597-66vd2mdu 227 7 for for IN cord-014597-66vd2mdu 227 8 the the DT cord-014597-66vd2mdu 227 9 changed change VBN cord-014597-66vd2mdu 227 10 feeding feeding NN cord-014597-66vd2mdu 227 11 strategy strategy NN cord-014597-66vd2mdu 227 12 ( ( -LRB- cord-014597-66vd2mdu 227 13 Fig Fig NNP cord-014597-66vd2mdu 227 14 . . . cord-014597-66vd2mdu 227 15 1c 1c NNP cord-014597-66vd2mdu 227 16 and and CC cord-014597-66vd2mdu 227 17 d d NNP cord-014597-66vd2mdu 227 18 ) ) -RRB- cord-014597-66vd2mdu 227 19 . . . cord-014597-66vd2mdu 228 1 As as IN cord-014597-66vd2mdu 228 2 expected expect VBN cord-014597-66vd2mdu 228 3 , , , cord-014597-66vd2mdu 228 4 the the DT cord-014597-66vd2mdu 228 5 glycation glycation NN cord-014597-66vd2mdu 228 6 level level NN cord-014597-66vd2mdu 228 7 decreased decrease VBD cord-014597-66vd2mdu 228 8 from from IN cord-014597-66vd2mdu 228 9 3 3 CD cord-014597-66vd2mdu 228 10 % % NN cord-014597-66vd2mdu 228 11 to to TO cord-014597-66vd2mdu 228 12 1 1 CD cord-014597-66vd2mdu 228 13 % % NN cord-014597-66vd2mdu 228 14 compared compare VBN cord-014597-66vd2mdu 228 15 to to IN cord-014597-66vd2mdu 228 16 the the DT cord-014597-66vd2mdu 228 17 reference reference NN cord-014597-66vd2mdu 228 18 culture culture NN cord-014597-66vd2mdu 228 19 . . . cord-014597-66vd2mdu 229 1 The the DT cord-014597-66vd2mdu 229 2 truncation truncation NN cord-014597-66vd2mdu 229 3 level level NN cord-014597-66vd2mdu 229 4 of of IN cord-014597-66vd2mdu 229 5 C c NN cord-014597-66vd2mdu 229 6 - - HYPH cord-014597-66vd2mdu 229 7 terminal terminal NN cord-014597-66vd2mdu 229 8 lysine lysine NN cord-014597-66vd2mdu 229 9 at at IN cord-014597-66vd2mdu 229 10 the the DT cord-014597-66vd2mdu 229 11 heavy heavy JJ cord-014597-66vd2mdu 229 12 chain chain NN cord-014597-66vd2mdu 229 13 of of IN cord-014597-66vd2mdu 229 14 the the DT cord-014597-66vd2mdu 229 15 mAB mAB NNPS cord-014597-66vd2mdu 229 16 increased increase VBD cord-014597-66vd2mdu 229 17 from from IN cord-014597-66vd2mdu 229 18 79 79 CD cord-014597-66vd2mdu 229 19 % % NN cord-014597-66vd2mdu 229 20 to to IN cord-014597-66vd2mdu 229 21 88 88 CD cord-014597-66vd2mdu 229 22 % % NN cord-014597-66vd2mdu 229 23 . . . cord-014597-66vd2mdu 230 1 The the DT cord-014597-66vd2mdu 230 2 glycosylation glycosylation NN cord-014597-66vd2mdu 230 3 was be VBD cord-014597-66vd2mdu 230 4 also also RB cord-014597-66vd2mdu 230 5 significantly significantly RB cord-014597-66vd2mdu 230 6 influenced influence VBN cord-014597-66vd2mdu 230 7 by by IN cord-014597-66vd2mdu 230 8 the the DT cord-014597-66vd2mdu 230 9 low low JJ cord-014597-66vd2mdu 230 10 nutrient nutrient NN cord-014597-66vd2mdu 230 11 level level NN cord-014597-66vd2mdu 230 12 ( ( -LRB- cord-014597-66vd2mdu 230 13 Fig Fig NNP cord-014597-66vd2mdu 230 14 . . . cord-014597-66vd2mdu 230 15 1e 1e NNP cord-014597-66vd2mdu 230 16 ) ) -RRB- cord-014597-66vd2mdu 230 17 : : : cord-014597-66vd2mdu 231 1 The the DT cord-014597-66vd2mdu 231 2 nonfucosylated nonfucosylated JJ cord-014597-66vd2mdu 231 3 variants variant NNS cord-014597-66vd2mdu 231 4 increased increase VBD cord-014597-66vd2mdu 231 5 from from IN cord-014597-66vd2mdu 231 6 3 3 CD cord-014597-66vd2mdu 231 7 % % NN cord-014597-66vd2mdu 231 8 to to TO cord-014597-66vd2mdu 231 9 6 6 CD cord-014597-66vd2mdu 231 10 % % NN cord-014597-66vd2mdu 231 11 ( ( -LRB- cord-014597-66vd2mdu 231 12 Fig Fig NNP cord-014597-66vd2mdu 231 13 . . . cord-014597-66vd2mdu 231 14 1f 1f CD cord-014597-66vd2mdu 231 15 ) ) -RRB- cord-014597-66vd2mdu 231 16 , , , cord-014597-66vd2mdu 231 17 the the DT cord-014597-66vd2mdu 231 18 degree degree NN cord-014597-66vd2mdu 231 19 of of IN cord-014597-66vd2mdu 231 20 galactosylation galactosylation NN cord-014597-66vd2mdu 231 21 increased increase VBD cord-014597-66vd2mdu 231 22 from from IN cord-014597-66vd2mdu 231 23 31 31 CD cord-014597-66vd2mdu 231 24 % % NN cord-014597-66vd2mdu 231 25 to to IN cord-014597-66vd2mdu 231 26 39 39 CD cord-014597-66vd2mdu 231 27 % % NN cord-014597-66vd2mdu 231 28 ( ( -LRB- cord-014597-66vd2mdu 231 29 Fig Fig NNP cord-014597-66vd2mdu 231 30 . . . cord-014597-66vd2mdu 231 31 1 1 CD cord-014597-66vd2mdu 231 32 g g NN cord-014597-66vd2mdu 231 33 ) ) -RRB- cord-014597-66vd2mdu 231 34 . . . cord-014597-66vd2mdu 232 1 Cultivation cultivation NN cord-014597-66vd2mdu 232 2 under under IN cord-014597-66vd2mdu 232 3 low low JJ cord-014597-66vd2mdu 232 4 nutrient nutrient NN cord-014597-66vd2mdu 232 5 level level NN cord-014597-66vd2mdu 232 6 led lead VBD cord-014597-66vd2mdu 232 7 to to IN cord-014597-66vd2mdu 232 8 54 54 CD cord-014597-66vd2mdu 232 9 % % NN cord-014597-66vd2mdu 232 10 higher high JJR cord-014597-66vd2mdu 232 11 viable viable JJ cord-014597-66vd2mdu 232 12 cell cell NN cord-014597-66vd2mdu 232 13 density density NN cord-014597-66vd2mdu 232 14 and and CC cord-014597-66vd2mdu 233 1 a a DT cord-014597-66vd2mdu 233 2 product product NN cord-014597-66vd2mdu 233 3 titer titer NN cord-014597-66vd2mdu 233 4 increased increase VBD cord-014597-66vd2mdu 233 5 by by IN cord-014597-66vd2mdu 233 6 109 109 CD cord-014597-66vd2mdu 233 7 % % NN cord-014597-66vd2mdu 233 8 when when WRB cord-014597-66vd2mdu 233 9 compared compare VBN cord-014597-66vd2mdu 233 10 to to IN cord-014597-66vd2mdu 233 11 reference reference NN cord-014597-66vd2mdu 233 12 culture culture NN cord-014597-66vd2mdu 233 13 grown grow VBN cord-014597-66vd2mdu 233 14 under under IN cord-014597-66vd2mdu 233 15 non non JJ cord-014597-66vd2mdu 233 16 - - JJ cord-014597-66vd2mdu 233 17 limiting limit VBG cord-014597-66vd2mdu 233 18 nutrient nutrient NN cord-014597-66vd2mdu 233 19 conditions condition NNS cord-014597-66vd2mdu 233 20 . . . cord-014597-66vd2mdu 234 1 The the DT cord-014597-66vd2mdu 234 2 analysis analysis NN cord-014597-66vd2mdu 234 3 of of IN cord-014597-66vd2mdu 234 4 product product NN cord-014597-66vd2mdu 234 5 quality quality NN cord-014597-66vd2mdu 234 6 reveals reveal VBZ cord-014597-66vd2mdu 234 7 75 75 CD cord-014597-66vd2mdu 234 8 % % NN cord-014597-66vd2mdu 234 9 less less JJR cord-014597-66vd2mdu 234 10 glycation glycation NN cord-014597-66vd2mdu 234 11 of of IN cord-014597-66vd2mdu 234 12 light light JJ cord-014597-66vd2mdu 234 13 chain chain NN cord-014597-66vd2mdu 234 14 for for IN cord-014597-66vd2mdu 234 15 CHO CHO NNP cord-014597-66vd2mdu 234 16 cells cell NNS cord-014597-66vd2mdu 234 17 grown grow VBN cord-014597-66vd2mdu 234 18 under under IN cord-014597-66vd2mdu 234 19 low low JJ cord-014597-66vd2mdu 234 20 nutrient nutrient NN cord-014597-66vd2mdu 234 21 conditions condition NNS cord-014597-66vd2mdu 234 22 ( ( -LRB- cord-014597-66vd2mdu 234 23 0.7 0.7 CD cord-014597-66vd2mdu 234 24 % % NN cord-014597-66vd2mdu 234 25 vs vs IN cord-014597-66vd2mdu 234 26 2.7 2.7 CD cord-014597-66vd2mdu 234 27 % % NN cord-014597-66vd2mdu 234 28 in in IN cord-014597-66vd2mdu 234 29 reference reference NN cord-014597-66vd2mdu 234 30 culture culture NN cord-014597-66vd2mdu 234 31 ) ) -RRB- cord-014597-66vd2mdu 234 32 . . . cord-014597-66vd2mdu 235 1 The the DT cord-014597-66vd2mdu 235 2 truncation truncation NN cord-014597-66vd2mdu 235 3 of of IN cord-014597-66vd2mdu 235 4 C c NN cord-014597-66vd2mdu 235 5 - - HYPH cord-014597-66vd2mdu 235 6 terminal terminal NN cord-014597-66vd2mdu 235 7 lysine lysine NN cord-014597-66vd2mdu 235 8 decreased decrease VBD cord-014597-66vd2mdu 235 9 by by IN cord-014597-66vd2mdu 235 10 10 10 CD cord-014597-66vd2mdu 235 11 % % NN cord-014597-66vd2mdu 235 12 ( ( -LRB- cord-014597-66vd2mdu 235 13 from from IN cord-014597-66vd2mdu 235 14 88 88 CD cord-014597-66vd2mdu 235 15 % % NN cord-014597-66vd2mdu 235 16 to to IN cord-014597-66vd2mdu 235 17 79 79 CD cord-014597-66vd2mdu 235 18 % % NN cord-014597-66vd2mdu 235 19 ) ) -RRB- cord-014597-66vd2mdu 235 20 , , , cord-014597-66vd2mdu 235 21 the the DT cord-014597-66vd2mdu 235 22 degree degree NN cord-014597-66vd2mdu 235 23 of of IN cord-014597-66vd2mdu 235 24 galactosylation galactosylation NN cord-014597-66vd2mdu 235 25 increased increase VBN cord-014597-66vd2mdu 235 26 by by IN cord-014597-66vd2mdu 235 27 23 23 CD cord-014597-66vd2mdu 235 28 % % NN cord-014597-66vd2mdu 235 29 ( ( -LRB- cord-014597-66vd2mdu 235 30 from from IN cord-014597-66vd2mdu 235 31 31 31 CD cord-014597-66vd2mdu 235 32 % % NN cord-014597-66vd2mdu 235 33 to to IN cord-014597-66vd2mdu 235 34 39 39 CD cord-014597-66vd2mdu 235 35 % % NN cord-014597-66vd2mdu 235 36 , , , cord-014597-66vd2mdu 235 37 also also RB cord-014597-66vd2mdu 235 38 observed observe VBN cord-014597-66vd2mdu 235 39 by by IN cord-014597-66vd2mdu 235 40 Takuma Takuma NNP cord-014597-66vd2mdu 235 41 et et NNP cord-014597-66vd2mdu 235 42 al al NNP cord-014597-66vd2mdu 235 43 . . . cord-014597-66vd2mdu 236 1 [ [ -LRB- cord-014597-66vd2mdu 236 2 2 2 CD cord-014597-66vd2mdu 236 3 ] ] -RRB- cord-014597-66vd2mdu 236 4 ) ) -RRB- cord-014597-66vd2mdu 237 1 and and CC cord-014597-66vd2mdu 237 2 non non JJ cord-014597-66vd2mdu 237 3 - - JJ cord-014597-66vd2mdu 237 4 fucosylated fucosylated JJ cord-014597-66vd2mdu 237 5 glycans glycan NNS cord-014597-66vd2mdu 237 6 increased increase VBN cord-014597-66vd2mdu 237 7 by by IN cord-014597-66vd2mdu 237 8 105 105 CD cord-014597-66vd2mdu 237 9 % % NN cord-014597-66vd2mdu 237 10 ( ( -LRB- cord-014597-66vd2mdu 237 11 from from IN cord-014597-66vd2mdu 237 12 2.8 2.8 CD cord-014597-66vd2mdu 237 13 % % NN cord-014597-66vd2mdu 237 14 to to IN cord-014597-66vd2mdu 237 15 5.8 5.8 CD cord-014597-66vd2mdu 237 16 % % NN cord-014597-66vd2mdu 237 17 ) ) -RRB- cord-014597-66vd2mdu 237 18 under under IN cord-014597-66vd2mdu 237 19 low low JJ cord-014597-66vd2mdu 237 20 nutrient nutrient NN cord-014597-66vd2mdu 237 21 conditions condition NNS cord-014597-66vd2mdu 237 22 . . . cord-014597-66vd2mdu 238 1 The the DT cord-014597-66vd2mdu 238 2 product product NN cord-014597-66vd2mdu 238 3 quality quality NN cord-014597-66vd2mdu 238 4 analysis analysis NN cord-014597-66vd2mdu 238 5 by by IN cord-014597-66vd2mdu 238 6 intact intact JJ cord-014597-66vd2mdu 238 7 mass mass NN cord-014597-66vd2mdu 238 8 proved prove VBD cord-014597-66vd2mdu 238 9 to to TO cord-014597-66vd2mdu 238 10 be be VB cord-014597-66vd2mdu 238 11 highly highly RB cord-014597-66vd2mdu 238 12 robust robust JJ cord-014597-66vd2mdu 238 13 ( ( -LRB- cord-014597-66vd2mdu 238 14 average average JJ cord-014597-66vd2mdu 238 15 CV cv NN cord-014597-66vd2mdu 238 16 for for IN cord-014597-66vd2mdu 238 17 four four CD cord-014597-66vd2mdu 238 18 replicates replicate NNS cord-014597-66vd2mdu 238 19 = = SYM cord-014597-66vd2mdu 238 20 2 2 CD cord-014597-66vd2mdu 238 21 % % NN cord-014597-66vd2mdu 238 22 ) ) -RRB- cord-014597-66vd2mdu 238 23 . . . cord-014597-66vd2mdu 239 1 In in IN cord-014597-66vd2mdu 239 2 summary summary NN cord-014597-66vd2mdu 239 3 , , , cord-014597-66vd2mdu 239 4 cultivation cultivation NN cord-014597-66vd2mdu 239 5 with with IN cord-014597-66vd2mdu 239 6 alternative alternative JJ cord-014597-66vd2mdu 239 7 feed feed NN cord-014597-66vd2mdu 239 8 led lead VBD cord-014597-66vd2mdu 239 9 to to IN cord-014597-66vd2mdu 239 10 higher high JJR cord-014597-66vd2mdu 239 11 IgG igg NN cord-014597-66vd2mdu 239 12 product product NN cord-014597-66vd2mdu 239 13 titer titer NN cord-014597-66vd2mdu 239 14 and and CC cord-014597-66vd2mdu 239 15 better well JJR cord-014597-66vd2mdu 239 16 product product NN cord-014597-66vd2mdu 239 17 quality quality NN cord-014597-66vd2mdu 239 18 ( ( -LRB- cord-014597-66vd2mdu 239 19 glycation glycation NN cord-014597-66vd2mdu 239 20 unwanted unwanted JJ cord-014597-66vd2mdu 239 21 , , , cord-014597-66vd2mdu 239 22 higher high JJR cord-014597-66vd2mdu 239 23 amount amount NN cord-014597-66vd2mdu 239 24 of of IN cord-014597-66vd2mdu 239 25 non non JJ cord-014597-66vd2mdu 239 26 - - JJ cord-014597-66vd2mdu 239 27 fucosylated fucosylated JJ cord-014597-66vd2mdu 239 28 glycans glycan NNS cord-014597-66vd2mdu 239 29 leads lead VBZ cord-014597-66vd2mdu 239 30 to to IN cord-014597-66vd2mdu 239 31 higher high JJR cord-014597-66vd2mdu 239 32 antibody antibody NN cord-014597-66vd2mdu 239 33 - - HYPH cord-014597-66vd2mdu 239 34 dependent dependent JJ cord-014597-66vd2mdu 239 35 cellmediated cellmediate VBN cord-014597-66vd2mdu 239 36 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 239 37 ( ( -LRB- cord-014597-66vd2mdu 239 38 ADCC ADCC NNP cord-014597-66vd2mdu 239 39 ) ) -RRB- cord-014597-66vd2mdu 239 40 , , , cord-014597-66vd2mdu 239 41 higher high JJR cord-014597-66vd2mdu 239 42 amount amount NN cord-014597-66vd2mdu 239 43 of of IN cord-014597-66vd2mdu 239 44 galactosylation galactosylation NN cord-014597-66vd2mdu 239 45 to to IN cord-014597-66vd2mdu 239 46 higher high JJR cord-014597-66vd2mdu 239 47 complement complement NN cord-014597-66vd2mdu 239 48 - - HYPH cord-014597-66vd2mdu 239 49 dependent dependent JJ cord-014597-66vd2mdu 239 50 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 239 51 ( ( -LRB- cord-014597-66vd2mdu 239 52 CDC CDC NNP cord-014597-66vd2mdu 239 53 ) ) -RRB- cord-014597-66vd2mdu 239 54 and and CC cord-014597-66vd2mdu 239 55 ADCC ADCC NNP cord-014597-66vd2mdu 239 56 [ [ -LRB- cord-014597-66vd2mdu 239 57 3 3 CD cord-014597-66vd2mdu 239 58 , , , cord-014597-66vd2mdu 239 59 4 4 CD cord-014597-66vd2mdu 239 60 ] ] -RRB- cord-014597-66vd2mdu 239 61 ) ) -RRB- cord-014597-66vd2mdu 239 62 . . . cord-014597-66vd2mdu 240 1 Background background NN cord-014597-66vd2mdu 241 1 We -PRON- PRP cord-014597-66vd2mdu 241 2 developed develop VBD cord-014597-66vd2mdu 241 3 an an DT cord-014597-66vd2mdu 241 4 automated automate VBN cord-014597-66vd2mdu 241 5 , , , cord-014597-66vd2mdu 241 6 multiwell multiwell NNP cord-014597-66vd2mdu 241 7 plate plate NN cord-014597-66vd2mdu 241 8 ( ( -LRB- cord-014597-66vd2mdu 241 9 MWP MWP NNP cord-014597-66vd2mdu 241 10 ) ) -RRB- cord-014597-66vd2mdu 241 11 based base VBN cord-014597-66vd2mdu 241 12 screening screening NN cord-014597-66vd2mdu 241 13 system system NN cord-014597-66vd2mdu 241 14 for for IN cord-014597-66vd2mdu 241 15 suspension suspension NN cord-014597-66vd2mdu 241 16 cell cell NN cord-014597-66vd2mdu 241 17 cultures culture NNS cord-014597-66vd2mdu 241 18 ( ( -LRB- cord-014597-66vd2mdu 241 19 Fig Fig NNP cord-014597-66vd2mdu 241 20 . . . cord-014597-66vd2mdu 241 21 1a 1a LS cord-014597-66vd2mdu 241 22 ) ) -RRB- cord-014597-66vd2mdu 241 23 which which WDT cord-014597-66vd2mdu 241 24 is be VBZ cord-014597-66vd2mdu 241 25 now now RB cord-014597-66vd2mdu 241 26 routinely routinely RB cord-014597-66vd2mdu 241 27 used use VBN cord-014597-66vd2mdu 241 28 in in IN cord-014597-66vd2mdu 241 29 cell cell NN cord-014597-66vd2mdu 241 30 culture culture NN cord-014597-66vd2mdu 241 31 process process NN cord-014597-66vd2mdu 241 32 development development NN cord-014597-66vd2mdu 241 33 . . . cord-014597-66vd2mdu 242 1 It -PRON- PRP cord-014597-66vd2mdu 242 2 is be VBZ cord-014597-66vd2mdu 242 3 characterized characterize VBN cord-014597-66vd2mdu 242 4 by by IN cord-014597-66vd2mdu 242 5 a a DT cord-014597-66vd2mdu 242 6 fully fully RB cord-014597-66vd2mdu 242 7 automated automate VBN cord-014597-66vd2mdu 242 8 workflow workflow NN cord-014597-66vd2mdu 242 9 with with IN cord-014597-66vd2mdu 242 10 integrated integrate VBN cord-014597-66vd2mdu 242 11 analytical analytical JJ cord-014597-66vd2mdu 242 12 instrumentation instrumentation NN cord-014597-66vd2mdu 242 13 . . . cord-014597-66vd2mdu 243 1 It -PRON- PRP cord-014597-66vd2mdu 243 2 uses use VBZ cord-014597-66vd2mdu 243 3 shaken shake VBN cord-014597-66vd2mdu 243 4 6 6 CD cord-014597-66vd2mdu 243 5 - - SYM cord-014597-66vd2mdu 243 6 24 24 CD cord-014597-66vd2mdu 243 7 well well NN cord-014597-66vd2mdu 243 8 plates plate NNS cord-014597-66vd2mdu 243 9 as as IN cord-014597-66vd2mdu 243 10 bioreactors bioreactor NNS cord-014597-66vd2mdu 243 11 which which WDT cord-014597-66vd2mdu 243 12 can can MD cord-014597-66vd2mdu 243 13 be be VB cord-014597-66vd2mdu 243 14 run run VBN cord-014597-66vd2mdu 243 15 in in IN cord-014597-66vd2mdu 243 16 batch batch NN cord-014597-66vd2mdu 243 17 and and CC cord-014597-66vd2mdu 243 18 fed fed JJ cord-014597-66vd2mdu 243 19 - - HYPH cord-014597-66vd2mdu 243 20 batch batch NN cord-014597-66vd2mdu 243 21 mode mode NN cord-014597-66vd2mdu 243 22 with with IN cord-014597-66vd2mdu 243 23 a a DT cord-014597-66vd2mdu 243 24 capacity capacity NN cord-014597-66vd2mdu 243 25 of of IN cord-014597-66vd2mdu 243 26 up up IN cord-014597-66vd2mdu 243 27 to to TO cord-014597-66vd2mdu 243 28 768 768 CD cord-014597-66vd2mdu 243 29 reactors reactor NNS cord-014597-66vd2mdu 243 30 in in IN cord-014597-66vd2mdu 243 31 parallel parallel NN cord-014597-66vd2mdu 243 32 [ [ -LRB- cord-014597-66vd2mdu 243 33 1 1 CD cord-014597-66vd2mdu 243 34 ] ] -RRB- cord-014597-66vd2mdu 243 35 [ [ -LRB- cord-014597-66vd2mdu 243 36 2 2 CD cord-014597-66vd2mdu 243 37 ] ] -RRB- cord-014597-66vd2mdu 243 38 [ [ -LRB- cord-014597-66vd2mdu 243 39 3 3 CD cord-014597-66vd2mdu 243 40 ] ] -RRB- cord-014597-66vd2mdu 243 41 . . . cord-014597-66vd2mdu 244 1 A a DT cord-014597-66vd2mdu 244 2 wide wide JJ cord-014597-66vd2mdu 244 3 ranging range VBG cord-014597-66vd2mdu 244 4 analytical analytical JJ cord-014597-66vd2mdu 244 5 portfolio portfolio NN cord-014597-66vd2mdu 244 6 to to TO cord-014597-66vd2mdu 244 7 monitor monitor VB cord-014597-66vd2mdu 244 8 cell cell NN cord-014597-66vd2mdu 244 9 culture culture NN cord-014597-66vd2mdu 244 10 processes process NNS cord-014597-66vd2mdu 244 11 and and CC cord-014597-66vd2mdu 244 12 also also RB cord-014597-66vd2mdu 244 13 a a DT cord-014597-66vd2mdu 244 14 cooperation cooperation NN cord-014597-66vd2mdu 244 15 with with IN cord-014597-66vd2mdu 244 16 internal internal JJ cord-014597-66vd2mdu 244 17 high high JJ cord-014597-66vd2mdu 244 18 throughput throughput NN cord-014597-66vd2mdu 244 19 ( ( -LRB- cord-014597-66vd2mdu 244 20 HT HT NNP cord-014597-66vd2mdu 244 21 ) ) -RRB- cord-014597-66vd2mdu 244 22 analytic analytic JJ cord-014597-66vd2mdu 244 23 groups group NNS cord-014597-66vd2mdu 244 24 to to TO cord-014597-66vd2mdu 244 25 characterize characterize VB cord-014597-66vd2mdu 244 26 product product NN cord-014597-66vd2mdu 244 27 quality quality NN cord-014597-66vd2mdu 244 28 are be VBP cord-014597-66vd2mdu 244 29 available available JJ cord-014597-66vd2mdu 244 30 . . . cord-014597-66vd2mdu 245 1 In in IN cord-014597-66vd2mdu 245 2 addition addition NN cord-014597-66vd2mdu 245 3 the the DT cord-014597-66vd2mdu 245 4 use use NN cord-014597-66vd2mdu 245 5 and and CC cord-014597-66vd2mdu 245 6 the the DT cord-014597-66vd2mdu 245 7 benefits benefit NNS cord-014597-66vd2mdu 245 8 of of IN cord-014597-66vd2mdu 245 9 spectroscopic spectroscopic JJ cord-014597-66vd2mdu 245 10 methods method NNS cord-014597-66vd2mdu 245 11 for for IN cord-014597-66vd2mdu 245 12 cell cell NN cord-014597-66vd2mdu 245 13 culture culture NN cord-014597-66vd2mdu 245 14 automation automation NN cord-014597-66vd2mdu 245 15 were be VBD cord-014597-66vd2mdu 245 16 shown show VBN cord-014597-66vd2mdu 245 17 in in IN cord-014597-66vd2mdu 245 18 the the DT cord-014597-66vd2mdu 245 19 past past NN cord-014597-66vd2mdu 245 20 [ [ -LRB- cord-014597-66vd2mdu 245 21 4 4 CD cord-014597-66vd2mdu 245 22 , , , cord-014597-66vd2mdu 245 23 5 5 CD cord-014597-66vd2mdu 245 24 ] ] -RRB- cord-014597-66vd2mdu 245 25 . . . cord-014597-66vd2mdu 246 1 Automated automated JJ cord-014597-66vd2mdu 246 2 cell cell NN cord-014597-66vd2mdu 246 3 culture culture NN cord-014597-66vd2mdu 246 4 systems system NNS cord-014597-66vd2mdu 246 5 enable enable VBP cord-014597-66vd2mdu 246 6 broader broad JJR cord-014597-66vd2mdu 246 7 screening screening NN cord-014597-66vd2mdu 246 8 within within IN cord-014597-66vd2mdu 246 9 a a DT cord-014597-66vd2mdu 246 10 shorter short JJR cord-014597-66vd2mdu 246 11 time time NN cord-014597-66vd2mdu 246 12 frame frame NN cord-014597-66vd2mdu 246 13 for for IN cord-014597-66vd2mdu 246 14 many many JJ cord-014597-66vd2mdu 246 15 applications application NNS cord-014597-66vd2mdu 246 16 in in IN cord-014597-66vd2mdu 246 17 upstream upstream JJ cord-014597-66vd2mdu 246 18 process process NN cord-014597-66vd2mdu 246 19 development development NN cord-014597-66vd2mdu 246 20 . . . cord-014597-66vd2mdu 247 1 The the DT cord-014597-66vd2mdu 247 2 higher high JJR cord-014597-66vd2mdu 247 3 degree degree NN cord-014597-66vd2mdu 247 4 of of IN cord-014597-66vd2mdu 247 5 parallelization parallelization NN cord-014597-66vd2mdu 247 6 and and CC cord-014597-66vd2mdu 247 7 automation automation NN cord-014597-66vd2mdu 247 8 helps help VBZ cord-014597-66vd2mdu 247 9 to to TO cord-014597-66vd2mdu 247 10 screen screen VB cord-014597-66vd2mdu 247 11 for for IN cord-014597-66vd2mdu 247 12 most most RBS cord-014597-66vd2mdu 247 13 promising promising JJ cord-014597-66vd2mdu 247 14 parameters parameter NNS cord-014597-66vd2mdu 247 15 in in IN cord-014597-66vd2mdu 247 16 a a DT cord-014597-66vd2mdu 247 17 shorter short JJR cord-014597-66vd2mdu 247 18 time time NN cord-014597-66vd2mdu 247 19 . . . cord-014597-66vd2mdu 248 1 The the DT cord-014597-66vd2mdu 248 2 use use NN cord-014597-66vd2mdu 248 3 of of IN cord-014597-66vd2mdu 248 4 broad broad JJ cord-014597-66vd2mdu 248 5 DoE DoE NNP cord-014597-66vd2mdu 248 6 screening screening NN cord-014597-66vd2mdu 248 7 design design NN cord-014597-66vd2mdu 248 8 allows allow VBZ cord-014597-66vd2mdu 248 9 in in IN cord-014597-66vd2mdu 248 10 addition addition NN cord-014597-66vd2mdu 248 11 the the DT cord-014597-66vd2mdu 248 12 identification identification NN cord-014597-66vd2mdu 248 13 of of IN cord-014597-66vd2mdu 248 14 parameters parameter NNS cord-014597-66vd2mdu 248 15 that that WDT cord-014597-66vd2mdu 248 16 support support VBP cord-014597-66vd2mdu 248 17 high high JJ cord-014597-66vd2mdu 248 18 titers titer NNS cord-014597-66vd2mdu 248 19 while while IN cord-014597-66vd2mdu 248 20 keeping keep VBG cord-014597-66vd2mdu 248 21 high high JJ cord-014597-66vd2mdu 248 22 product product NN cord-014597-66vd2mdu 248 23 quality quality NN cord-014597-66vd2mdu 248 24 ( ( -LRB- cord-014597-66vd2mdu 248 25 multiple multiple JJ cord-014597-66vd2mdu 248 26 factors factor NNS cord-014597-66vd2mdu 248 27 at at IN cord-014597-66vd2mdu 248 28 the the DT cord-014597-66vd2mdu 248 29 same same JJ cord-014597-66vd2mdu 248 30 time time NN cord-014597-66vd2mdu 248 31 ) ) -RRB- cord-014597-66vd2mdu 248 32 . . . cord-014597-66vd2mdu 249 1 The the DT cord-014597-66vd2mdu 249 2 illustration illustration NN cord-014597-66vd2mdu 249 3 ( ( -LRB- cord-014597-66vd2mdu 249 4 Fig Fig NNP cord-014597-66vd2mdu 249 5 . . . cord-014597-66vd2mdu 249 6 1b 1b CD cord-014597-66vd2mdu 249 7 ) ) -RRB- cord-014597-66vd2mdu 249 8 shows show VBZ cord-014597-66vd2mdu 249 9 an an DT cord-014597-66vd2mdu 249 10 example example NN cord-014597-66vd2mdu 249 11 how how WRB cord-014597-66vd2mdu 249 12 this this DT cord-014597-66vd2mdu 249 13 combination combination NN cord-014597-66vd2mdu 249 14 can can MD cord-014597-66vd2mdu 249 15 speed speed VB cord-014597-66vd2mdu 249 16 up up RP cord-014597-66vd2mdu 249 17 process process NN cord-014597-66vd2mdu 249 18 development development NN cord-014597-66vd2mdu 249 19 steps step NNS cord-014597-66vd2mdu 249 20 . . . cord-014597-66vd2mdu 250 1 Main main JJ cord-014597-66vd2mdu 250 2 applications application NNS cord-014597-66vd2mdu 250 3 of of IN cord-014597-66vd2mdu 250 4 the the DT cord-014597-66vd2mdu 250 5 cell cell NN cord-014597-66vd2mdu 250 6 culture culture NN cord-014597-66vd2mdu 250 7 automation automation NN cord-014597-66vd2mdu 250 8 are be VBP cord-014597-66vd2mdu 250 9 for for IN cord-014597-66vd2mdu 250 10 example example NN cord-014597-66vd2mdu 250 11 the the DT cord-014597-66vd2mdu 250 12 identification identification NN cord-014597-66vd2mdu 250 13 of of IN cord-014597-66vd2mdu 250 14 product product NN cord-014597-66vd2mdu 250 15 quality quality NN cord-014597-66vd2mdu 250 16 levers lever NNS cord-014597-66vd2mdu 250 17 and and CC cord-014597-66vd2mdu 250 18 media medium NNS cord-014597-66vd2mdu 250 19 or or CC cord-014597-66vd2mdu 250 20 feed feed NN cord-014597-66vd2mdu 250 21 optimization optimization NN cord-014597-66vd2mdu 250 22 . . . cord-014597-66vd2mdu 251 1 The the DT cord-014597-66vd2mdu 251 2 application application NN cord-014597-66vd2mdu 251 3 of of IN cord-014597-66vd2mdu 251 4 the the DT cord-014597-66vd2mdu 251 5 cell cell NN cord-014597-66vd2mdu 251 6 culture culture NN cord-014597-66vd2mdu 251 7 automation automation NN cord-014597-66vd2mdu 251 8 is be VBZ cord-014597-66vd2mdu 251 9 shown show VBN cord-014597-66vd2mdu 251 10 for for IN cord-014597-66vd2mdu 251 11 two two CD cord-014597-66vd2mdu 251 12 examples example NNS cord-014597-66vd2mdu 251 13 . . . cord-014597-66vd2mdu 252 1 The the DT cord-014597-66vd2mdu 252 2 goal goal NN cord-014597-66vd2mdu 252 3 in in IN cord-014597-66vd2mdu 252 4 the the DT cord-014597-66vd2mdu 252 5 first first JJ cord-014597-66vd2mdu 252 6 application application NN cord-014597-66vd2mdu 252 7 was be VBD cord-014597-66vd2mdu 252 8 to to TO cord-014597-66vd2mdu 252 9 identify identify VB cord-014597-66vd2mdu 252 10 levers lever NNS cord-014597-66vd2mdu 252 11 to to TO cord-014597-66vd2mdu 252 12 reduce reduce VB cord-014597-66vd2mdu 252 13 trisulfides trisulfide NNS cord-014597-66vd2mdu 252 14 . . . cord-014597-66vd2mdu 253 1 By by IN cord-014597-66vd2mdu 253 2 a a DT cord-014597-66vd2mdu 253 3 screening screening NN cord-014597-66vd2mdu 253 4 of of IN cord-014597-66vd2mdu 253 5 39 39 CD cord-014597-66vd2mdu 253 6 conditions condition NNS cord-014597-66vd2mdu 253 7 in in IN cord-014597-66vd2mdu 253 8 parallel parallel NN cord-014597-66vd2mdu 253 9 ( ( -LRB- cord-014597-66vd2mdu 253 10 in in IN cord-014597-66vd2mdu 253 11 4-fold 4-fold CD cord-014597-66vd2mdu 253 12 replication replication NN cord-014597-66vd2mdu 253 13 , , , cord-014597-66vd2mdu 253 14 158 158 CD cord-014597-66vd2mdu 253 15 wells well NNS cord-014597-66vd2mdu 253 16 in in IN cord-014597-66vd2mdu 253 17 sum sum NN cord-014597-66vd2mdu 253 18 ) ) -RRB- cord-014597-66vd2mdu 254 1 the the DT cord-014597-66vd2mdu 254 2 reduction reduction NN cord-014597-66vd2mdu 254 3 of of IN cord-014597-66vd2mdu 254 4 Trisulfides Trisulfides NNP cord-014597-66vd2mdu 254 5 by by IN cord-014597-66vd2mdu 254 6 97.5 97.5 CD cord-014597-66vd2mdu 254 7 % % NN cord-014597-66vd2mdu 254 8 ( ( -LRB- cord-014597-66vd2mdu 254 9 normalized normalize VBN cord-014597-66vd2mdu 254 10 to to TO cord-014597-66vd2mdu 254 11 start start VB cord-014597-66vd2mdu 254 12 level level NN cord-014597-66vd2mdu 254 13 ) ) -RRB- cord-014597-66vd2mdu 254 14 was be VBD cord-014597-66vd2mdu 254 15 possible possible JJ cord-014597-66vd2mdu 254 16 . . . cord-014597-66vd2mdu 255 1 In in IN cord-014597-66vd2mdu 255 2 addition addition NN cord-014597-66vd2mdu 255 3 the the DT cord-014597-66vd2mdu 255 4 levers lever NNS cord-014597-66vd2mdu 255 5 for for IN cord-014597-66vd2mdu 255 6 Trisulfide Trisulfide NNP cord-014597-66vd2mdu 255 7 reduction reduction NN cord-014597-66vd2mdu 255 8 were be VBD cord-014597-66vd2mdu 255 9 identified identify VBN cord-014597-66vd2mdu 255 10 . . . cord-014597-66vd2mdu 256 1 The the DT cord-014597-66vd2mdu 256 2 best good JJS cord-014597-66vd2mdu 256 3 and and CC cord-014597-66vd2mdu 256 4 start start VB cord-014597-66vd2mdu 256 5 conditions condition NNS cord-014597-66vd2mdu 256 6 were be VBD cord-014597-66vd2mdu 256 7 verified verify VBN cord-014597-66vd2mdu 256 8 in in IN cord-014597-66vd2mdu 256 9 bioreactor bioreactor NN cord-014597-66vd2mdu 256 10 scale scale NN cord-014597-66vd2mdu 256 11 ( ( -LRB- cord-014597-66vd2mdu 256 12 Fig Fig NNP cord-014597-66vd2mdu 256 13 . . . cord-014597-66vd2mdu 256 14 1c 1c CD cord-014597-66vd2mdu 256 15 ) ) -RRB- cord-014597-66vd2mdu 256 16 . . . cord-014597-66vd2mdu 257 1 The the DT cord-014597-66vd2mdu 257 2 goal goal NN cord-014597-66vd2mdu 257 3 in in IN cord-014597-66vd2mdu 257 4 the the DT cord-014597-66vd2mdu 257 5 second second JJ cord-014597-66vd2mdu 257 6 application application NN cord-014597-66vd2mdu 257 7 was be VBD cord-014597-66vd2mdu 257 8 to to TO cord-014597-66vd2mdu 257 9 increase increase VB cord-014597-66vd2mdu 257 10 product product NN cord-014597-66vd2mdu 257 11 concentration concentration NN cord-014597-66vd2mdu 257 12 without without IN cord-014597-66vd2mdu 257 13 an an DT cord-014597-66vd2mdu 257 14 impact impact NN cord-014597-66vd2mdu 257 15 on on IN cord-014597-66vd2mdu 257 16 product product NN cord-014597-66vd2mdu 257 17 quality quality NN cord-014597-66vd2mdu 257 18 . . . cord-014597-66vd2mdu 258 1 By by IN cord-014597-66vd2mdu 258 2 a a DT cord-014597-66vd2mdu 258 3 screening screening NN cord-014597-66vd2mdu 258 4 of of IN cord-014597-66vd2mdu 258 5 54 54 CD cord-014597-66vd2mdu 258 6 conditions condition NNS cord-014597-66vd2mdu 258 7 in in IN cord-014597-66vd2mdu 258 8 parallel parallel NN cord-014597-66vd2mdu 258 9 ( ( -LRB- cord-014597-66vd2mdu 258 10 in in IN cord-014597-66vd2mdu 258 11 4-fold 4-fold CD cord-014597-66vd2mdu 258 12 replication replication NN cord-014597-66vd2mdu 258 13 , , , cord-014597-66vd2mdu 258 14 216 216 CD cord-014597-66vd2mdu 258 15 wells well NNS cord-014597-66vd2mdu 258 16 in in IN cord-014597-66vd2mdu 258 17 sum sum NN cord-014597-66vd2mdu 258 18 ) ) -RRB- cord-014597-66vd2mdu 259 1 the the DT cord-014597-66vd2mdu 259 2 increase increase NN cord-014597-66vd2mdu 259 3 of of IN cord-014597-66vd2mdu 259 4 titer titer NN cord-014597-66vd2mdu 259 5 from from IN cord-014597-66vd2mdu 259 6 1.5 1.5 CD cord-014597-66vd2mdu 259 7 g g NN cord-014597-66vd2mdu 259 8 / / SYM cord-014597-66vd2mdu 259 9 L l NN cord-014597-66vd2mdu 259 10 to to IN cord-014597-66vd2mdu 259 11 3.7 3.7 CD cord-014597-66vd2mdu 259 12 g g NN cord-014597-66vd2mdu 259 13 / / SYM cord-014597-66vd2mdu 259 14 L l NN cord-014597-66vd2mdu 259 15 ( ( -LRB- cord-014597-66vd2mdu 259 16 > > XX cord-014597-66vd2mdu 260 1 factor factor NN cord-014597-66vd2mdu 260 2 2 2 CD cord-014597-66vd2mdu 260 3 ) ) -RRB- cord-014597-66vd2mdu 260 4 was be VBD cord-014597-66vd2mdu 260 5 possible possible JJ cord-014597-66vd2mdu 260 6 by by IN cord-014597-66vd2mdu 260 7 media medium NNS cord-014597-66vd2mdu 260 8 platform platform NN cord-014597-66vd2mdu 260 9 change change NN cord-014597-66vd2mdu 260 10 and and CC cord-014597-66vd2mdu 260 11 media medium NNS cord-014597-66vd2mdu 260 12 optimization optimization NN cord-014597-66vd2mdu 260 13 . . . cord-014597-66vd2mdu 261 1 An an DT cord-014597-66vd2mdu 261 2 impact impact NN cord-014597-66vd2mdu 261 3 on on IN cord-014597-66vd2mdu 261 4 product product NN cord-014597-66vd2mdu 261 5 quality quality NN cord-014597-66vd2mdu 261 6 could could MD cord-014597-66vd2mdu 261 7 not not RB cord-014597-66vd2mdu 261 8 been be VBN cord-014597-66vd2mdu 261 9 shown show VBN cord-014597-66vd2mdu 261 10 . . . cord-014597-66vd2mdu 262 1 The the DT cord-014597-66vd2mdu 262 2 best good JJS cord-014597-66vd2mdu 262 3 conditions condition NNS cord-014597-66vd2mdu 262 4 were be VBD cord-014597-66vd2mdu 262 5 also also RB cord-014597-66vd2mdu 262 6 verified verify VBN cord-014597-66vd2mdu 262 7 in in IN cord-014597-66vd2mdu 262 8 bioreactor bioreactor NN cord-014597-66vd2mdu 262 9 scale scale NN cord-014597-66vd2mdu 262 10 ( ( -LRB- cord-014597-66vd2mdu 262 11 Fig Fig NNP cord-014597-66vd2mdu 262 12 . . . cord-014597-66vd2mdu 262 13 1d 1d CD cord-014597-66vd2mdu 262 14 ) ) -RRB- cord-014597-66vd2mdu 262 15 . . . cord-014597-66vd2mdu 263 1 The the DT cord-014597-66vd2mdu 263 2 benefits benefit NNS cord-014597-66vd2mdu 263 3 of of IN cord-014597-66vd2mdu 263 4 using use VBG cord-014597-66vd2mdu 263 5 cell cell NN cord-014597-66vd2mdu 263 6 culture culture NN cord-014597-66vd2mdu 263 7 automation automation NN cord-014597-66vd2mdu 263 8 in in IN cord-014597-66vd2mdu 263 9 late late JJ cord-014597-66vd2mdu 263 10 stage stage NN cord-014597-66vd2mdu 263 11 process process NN cord-014597-66vd2mdu 263 12 development development NN cord-014597-66vd2mdu 263 13 were be VBD cord-014597-66vd2mdu 263 14 shown show VBN cord-014597-66vd2mdu 263 15 based base VBN cord-014597-66vd2mdu 263 16 on on IN cord-014597-66vd2mdu 263 17 two two CD cord-014597-66vd2mdu 263 18 examples example NNS cord-014597-66vd2mdu 263 19 of of IN cord-014597-66vd2mdu 263 20 current current JJ cord-014597-66vd2mdu 263 21 applications application NNS cord-014597-66vd2mdu 263 22 . . . cord-014597-66vd2mdu 264 1 For for IN cord-014597-66vd2mdu 264 2 this this DT cord-014597-66vd2mdu 264 3 purpose purpose NN cord-014597-66vd2mdu 264 4 the the DT cord-014597-66vd2mdu 264 5 experimental experimental JJ cord-014597-66vd2mdu 264 6 results result NNS cord-014597-66vd2mdu 264 7 of of IN cord-014597-66vd2mdu 264 8 the the DT cord-014597-66vd2mdu 264 9 development development NN cord-014597-66vd2mdu 264 10 work work NN cord-014597-66vd2mdu 264 11 of of IN cord-014597-66vd2mdu 264 12 two two CD cord-014597-66vd2mdu 264 13 late late JJ cord-014597-66vd2mdu 264 14 state state NN cord-014597-66vd2mdu 264 15 projects project NNS cord-014597-66vd2mdu 264 16 using use VBG cord-014597-66vd2mdu 264 17 the the DT cord-014597-66vd2mdu 264 18 in in IN cord-014597-66vd2mdu 264 19 - - HYPH cord-014597-66vd2mdu 264 20 house house NN cord-014597-66vd2mdu 264 21 developed develop VBD cord-014597-66vd2mdu 264 22 automated automated JJ cord-014597-66vd2mdu 264 23 cell cell NN cord-014597-66vd2mdu 264 24 culture culture NN cord-014597-66vd2mdu 264 25 system system NN cord-014597-66vd2mdu 264 26 were be VBD cord-014597-66vd2mdu 264 27 shown show VBN cord-014597-66vd2mdu 264 28 . . . cord-014597-66vd2mdu 265 1 The the DT cord-014597-66vd2mdu 265 2 first first JJ cord-014597-66vd2mdu 265 3 example example NN cord-014597-66vd2mdu 265 4 shows show VBZ cord-014597-66vd2mdu 265 5 the the DT cord-014597-66vd2mdu 265 6 capability capability NN cord-014597-66vd2mdu 265 7 of of IN cord-014597-66vd2mdu 265 8 the the DT cord-014597-66vd2mdu 265 9 automated automate VBN cord-014597-66vd2mdu 265 10 cell cell NN cord-014597-66vd2mdu 265 11 culture culture NN cord-014597-66vd2mdu 265 12 system system NN cord-014597-66vd2mdu 265 13 by by IN cord-014597-66vd2mdu 265 14 reducing reduce VBG cord-014597-66vd2mdu 265 15 trisulfides trisulfide NNS cord-014597-66vd2mdu 265 16 significantly significantly RB cord-014597-66vd2mdu 265 17 in in IN cord-014597-66vd2mdu 265 18 just just RB cord-014597-66vd2mdu 265 19 one one CD cord-014597-66vd2mdu 265 20 experiment experiment NN cord-014597-66vd2mdu 265 21 . . . cord-014597-66vd2mdu 266 1 For for IN cord-014597-66vd2mdu 266 2 the the DT cord-014597-66vd2mdu 266 3 other other JJ cord-014597-66vd2mdu 266 4 project project NN cord-014597-66vd2mdu 266 5 the the DT cord-014597-66vd2mdu 266 6 final final JJ cord-014597-66vd2mdu 266 7 product product NN cord-014597-66vd2mdu 266 8 concentration concentration NN cord-014597-66vd2mdu 266 9 could could MD cord-014597-66vd2mdu 266 10 be be VB cord-014597-66vd2mdu 266 11 increased increase VBN cord-014597-66vd2mdu 266 12 by by IN cord-014597-66vd2mdu 266 13 factor factor NN cord-014597-66vd2mdu 266 14 2.5 2.5 CD cord-014597-66vd2mdu 266 15 by by IN cord-014597-66vd2mdu 266 16 a a DT cord-014597-66vd2mdu 266 17 media medium NNS cord-014597-66vd2mdu 266 18 screening screening NN cord-014597-66vd2mdu 266 19 and and CC cord-014597-66vd2mdu 266 20 changing change VBG cord-014597-66vd2mdu 266 21 to to IN cord-014597-66vd2mdu 266 22 the the DT cord-014597-66vd2mdu 266 23 in in IN cord-014597-66vd2mdu 266 24 - - HYPH cord-014597-66vd2mdu 266 25 house house NN cord-014597-66vd2mdu 266 26 media medium NNS cord-014597-66vd2mdu 266 27 platform platform NN cord-014597-66vd2mdu 266 28 . . . cord-014597-66vd2mdu 267 1 These these DT cord-014597-66vd2mdu 267 2 two two CD cord-014597-66vd2mdu 267 3 examples example NNS cord-014597-66vd2mdu 267 4 show show VBP cord-014597-66vd2mdu 267 5 the the DT cord-014597-66vd2mdu 267 6 potential potential NN cord-014597-66vd2mdu 267 7 of of IN cord-014597-66vd2mdu 267 8 cell cell NN cord-014597-66vd2mdu 267 9 culture culture NN cord-014597-66vd2mdu 267 10 automation automation NN cord-014597-66vd2mdu 267 11 as as IN cord-014597-66vd2mdu 267 12 a a DT cord-014597-66vd2mdu 267 13 routine routine JJ cord-014597-66vd2mdu 267 14 tool tool NN cord-014597-66vd2mdu 267 15 in in IN cord-014597-66vd2mdu 267 16 process process NN cord-014597-66vd2mdu 267 17 development development NN cord-014597-66vd2mdu 267 18 . . . cord-014597-66vd2mdu 268 1 The the DT cord-014597-66vd2mdu 268 2 cell cell NN cord-014597-66vd2mdu 268 3 line line NN cord-014597-66vd2mdu 268 4 development development NN cord-014597-66vd2mdu 268 5 process process NN cord-014597-66vd2mdu 268 6 has have VBZ cord-014597-66vd2mdu 268 7 become become VBN cord-014597-66vd2mdu 268 8 faster fast RBR cord-014597-66vd2mdu 268 9 and and CC cord-014597-66vd2mdu 268 10 is be VBZ cord-014597-66vd2mdu 268 11 simultaneously simultaneously RB cord-014597-66vd2mdu 268 12 generating generate VBG cord-014597-66vd2mdu 268 13 more more JJR cord-014597-66vd2mdu 268 14 clone clone NN cord-014597-66vd2mdu 268 15 - - HYPH cord-014597-66vd2mdu 268 16 and and CC cord-014597-66vd2mdu 268 17 product product NN cord-014597-66vd2mdu 268 18 - - HYPH cord-014597-66vd2mdu 268 19 related relate VBN cord-014597-66vd2mdu 268 20 analytical analytical JJ cord-014597-66vd2mdu 268 21 data datum NNS cord-014597-66vd2mdu 268 22 . . . cord-014597-66vd2mdu 269 1 In in IN cord-014597-66vd2mdu 269 2 order order NN cord-014597-66vd2mdu 269 3 to to TO cord-014597-66vd2mdu 269 4 select select VB cord-014597-66vd2mdu 269 5 the the DT cord-014597-66vd2mdu 269 6 best good JJS cord-014597-66vd2mdu 269 7 producer producer NN cord-014597-66vd2mdu 269 8 cell cell NN cord-014597-66vd2mdu 269 9 line line NN cord-014597-66vd2mdu 269 10 , , , cord-014597-66vd2mdu 269 11 extremely extremely RB cord-014597-66vd2mdu 269 12 heterogeneous heterogeneous JJ cord-014597-66vd2mdu 269 13 data datum NNS cord-014597-66vd2mdu 269 14 types type NNS cord-014597-66vd2mdu 269 15 need need VBP cord-014597-66vd2mdu 269 16 to to TO cord-014597-66vd2mdu 269 17 be be VB cord-014597-66vd2mdu 269 18 systematically systematically RB cord-014597-66vd2mdu 269 19 compared compare VBN cord-014597-66vd2mdu 269 20 . . . cord-014597-66vd2mdu 270 1 The the DT cord-014597-66vd2mdu 270 2 timely timely JJ cord-014597-66vd2mdu 270 3 availability availability NN cord-014597-66vd2mdu 270 4 of of IN cord-014597-66vd2mdu 270 5 all all DT cord-014597-66vd2mdu 270 6 data datum NNS cord-014597-66vd2mdu 270 7 needed need VBN cord-014597-66vd2mdu 270 8 to to TO cord-014597-66vd2mdu 270 9 decide decide VB cord-014597-66vd2mdu 270 10 which which WDT cord-014597-66vd2mdu 270 11 cell cell NN cord-014597-66vd2mdu 270 12 line line NN cord-014597-66vd2mdu 270 13 to to TO cord-014597-66vd2mdu 270 14 pursue pursue VB cord-014597-66vd2mdu 270 15 has have VBZ cord-014597-66vd2mdu 270 16 become become VBN cord-014597-66vd2mdu 270 17 a a DT cord-014597-66vd2mdu 270 18 bottleneck bottleneck NN cord-014597-66vd2mdu 270 19 in in IN cord-014597-66vd2mdu 270 20 the the DT cord-014597-66vd2mdu 270 21 cell cell NN cord-014597-66vd2mdu 270 22 line line NN cord-014597-66vd2mdu 270 23 development development NN cord-014597-66vd2mdu 270 24 workflow workflow NN cord-014597-66vd2mdu 270 25 . . . cord-014597-66vd2mdu 271 1 To to TO cord-014597-66vd2mdu 271 2 ensure ensure VB cord-014597-66vd2mdu 271 3 sound sound JJ cord-014597-66vd2mdu 271 4 decision decision NN cord-014597-66vd2mdu 271 5 making making NN cord-014597-66vd2mdu 271 6 , , , cord-014597-66vd2mdu 271 7 new new JJ cord-014597-66vd2mdu 271 8 integrated integrated JJ cord-014597-66vd2mdu 271 9 workflow workflow NN cord-014597-66vd2mdu 271 10 support support NN cord-014597-66vd2mdu 271 11 and and CC cord-014597-66vd2mdu 271 12 data data NN cord-014597-66vd2mdu 271 13 analysis analysis NN cord-014597-66vd2mdu 271 14 methods method NNS cord-014597-66vd2mdu 271 15 are be VBP cord-014597-66vd2mdu 271 16 needed need VBN cord-014597-66vd2mdu 271 17 . . . cord-014597-66vd2mdu 272 1 We -PRON- PRP cord-014597-66vd2mdu 272 2 have have VBP cord-014597-66vd2mdu 272 3 developed develop VBN cord-014597-66vd2mdu 272 4 a a DT cord-014597-66vd2mdu 272 5 new new JJ cord-014597-66vd2mdu 272 6 end end NN cord-014597-66vd2mdu 272 7 - - HYPH cord-014597-66vd2mdu 272 8 to to IN cord-014597-66vd2mdu 272 9 - - HYPH cord-014597-66vd2mdu 272 10 end end NN cord-014597-66vd2mdu 272 11 platform platform NN cord-014597-66vd2mdu 272 12 for for IN cord-014597-66vd2mdu 272 13 bioprocess bioprocess NNP cord-014597-66vd2mdu 272 14 development development NNP cord-014597-66vd2mdu 272 15 , , , cord-014597-66vd2mdu 272 16 which which WDT cord-014597-66vd2mdu 272 17 includes include VBZ cord-014597-66vd2mdu 272 18 a a DT cord-014597-66vd2mdu 272 19 cell cell NN cord-014597-66vd2mdu 272 20 line line NN cord-014597-66vd2mdu 272 21 development development NN cord-014597-66vd2mdu 272 22 workflow workflow NN cord-014597-66vd2mdu 272 23 system system NN cord-014597-66vd2mdu 272 24 supporting support VBG cord-014597-66vd2mdu 272 25 seeding seeding NN cord-014597-66vd2mdu 272 26 , , , cord-014597-66vd2mdu 272 27 selection selection NN cord-014597-66vd2mdu 272 28 , , , cord-014597-66vd2mdu 272 29 passaging passaging NN cord-014597-66vd2mdu 272 30 , , , cord-014597-66vd2mdu 272 31 analyzing analyze VBG cord-014597-66vd2mdu 272 32 , , , cord-014597-66vd2mdu 272 33 cryo cryo NN cord-014597-66vd2mdu 272 34 - - HYPH cord-014597-66vd2mdu 272 35 conservation conservation NN cord-014597-66vd2mdu 272 36 , , , cord-014597-66vd2mdu 272 37 and and CC cord-014597-66vd2mdu 272 38 processing processing NN cord-014597-66vd2mdu 272 39 in in IN cord-014597-66vd2mdu 272 40 ( ( -LRB- cord-014597-66vd2mdu 272 41 micro- micro- NN cord-014597-66vd2mdu 272 42 ) ) -RRB- cord-014597-66vd2mdu 272 43 bioreactors bioreactor NNS cord-014597-66vd2mdu 272 44 . . . cord-014597-66vd2mdu 273 1 This this DT cord-014597-66vd2mdu 273 2 platform platform NN cord-014597-66vd2mdu 273 3 , , , cord-014597-66vd2mdu 273 4 Genedata Genedata NNP cord-014597-66vd2mdu 273 5 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 273 6 ™ ™ NN cord-014597-66vd2mdu 273 7 , , , cord-014597-66vd2mdu 273 8 enables enable VBZ cord-014597-66vd2mdu 273 9 partially partially RB cord-014597-66vd2mdu 273 10 or or CC cord-014597-66vd2mdu 273 11 fully fully RB cord-014597-66vd2mdu 273 12 automated automate VBN cord-014597-66vd2mdu 273 13 cell cell NN cord-014597-66vd2mdu 273 14 line line NN cord-014597-66vd2mdu 273 15 selection selection NN cord-014597-66vd2mdu 273 16 and and CC cord-014597-66vd2mdu 273 17 assessment assessment NN cord-014597-66vd2mdu 273 18 processes process NNS cord-014597-66vd2mdu 273 19 , , , cord-014597-66vd2mdu 273 20 and and CC cord-014597-66vd2mdu 273 21 it -PRON- PRP cord-014597-66vd2mdu 273 22 increases increase VBZ cord-014597-66vd2mdu 273 23 process process NN cord-014597-66vd2mdu 273 24 efficiency efficiency NN cord-014597-66vd2mdu 273 25 and and CC cord-014597-66vd2mdu 273 26 quality quality NN cord-014597-66vd2mdu 273 27 . . . cord-014597-66vd2mdu 274 1 The the DT cord-014597-66vd2mdu 274 2 system system NN cord-014597-66vd2mdu 274 3 tracks track VBZ cord-014597-66vd2mdu 274 4 the the DT cord-014597-66vd2mdu 274 5 full full JJ cord-014597-66vd2mdu 274 6 history history NN cord-014597-66vd2mdu 274 7 of of IN cord-014597-66vd2mdu 274 8 all all DT cord-014597-66vd2mdu 274 9 clones clone NNS cord-014597-66vd2mdu 274 10 -from -from IN cord-014597-66vd2mdu 274 11 initial initial JJ cord-014597-66vd2mdu 274 12 transfection transfection NN cord-014597-66vd2mdu 274 13 all all PDT cord-014597-66vd2mdu 274 14 the the DT cord-014597-66vd2mdu 274 15 way way NN cord-014597-66vd2mdu 274 16 to to IN cord-014597-66vd2mdu 274 17 their -PRON- PRP$ cord-014597-66vd2mdu 274 18 evaluation evaluation NN cord-014597-66vd2mdu 274 19 in in IN cord-014597-66vd2mdu 274 20 bioreactor bioreactor NN cord-014597-66vd2mdu 274 21 runs run NNS cord-014597-66vd2mdu 274 22 -and -and POS cord-014597-66vd2mdu 274 23 combines combine VBZ cord-014597-66vd2mdu 274 24 this this DT cord-014597-66vd2mdu 274 25 information information NN cord-014597-66vd2mdu 274 26 with with IN cord-014597-66vd2mdu 274 27 analytics analytic NNS cord-014597-66vd2mdu 274 28 data datum NNS cord-014597-66vd2mdu 274 29 on on IN cord-014597-66vd2mdu 274 30 molecules molecule NNS cord-014597-66vd2mdu 274 31 , , , cord-014597-66vd2mdu 274 32 clones clone NNS cord-014597-66vd2mdu 274 33 , , , cord-014597-66vd2mdu 274 34 and and CC cord-014597-66vd2mdu 274 35 product product NN cord-014597-66vd2mdu 274 36 quality quality NN cord-014597-66vd2mdu 274 37 . . . cord-014597-66vd2mdu 275 1 It -PRON- PRP cord-014597-66vd2mdu 275 2 can can MD cord-014597-66vd2mdu 275 3 directly directly RB cord-014597-66vd2mdu 275 4 integrate integrate VB cord-014597-66vd2mdu 275 5 with with IN cord-014597-66vd2mdu 275 6 all all DT cord-014597-66vd2mdu 275 7 instruments instrument NNS cord-014597-66vd2mdu 275 8 , , , cord-014597-66vd2mdu 275 9 such such JJ cord-014597-66vd2mdu 275 10 as as IN cord-014597-66vd2mdu 275 11 pipetting pipetting JJ cord-014597-66vd2mdu 275 12 robots robot NNS cord-014597-66vd2mdu 275 13 , , , cord-014597-66vd2mdu 275 14 bioreactors bioreactor NNS cord-014597-66vd2mdu 275 15 , , , cord-014597-66vd2mdu 275 16 and and CC cord-014597-66vd2mdu 275 17 bioanalyzers bioanalyzer NNS cord-014597-66vd2mdu 275 18 . . . cord-014597-66vd2mdu 276 1 The the DT cord-014597-66vd2mdu 276 2 system system NN cord-014597-66vd2mdu 276 3 is be VBZ cord-014597-66vd2mdu 276 4 designed design VBN cord-014597-66vd2mdu 276 5 for for IN cord-014597-66vd2mdu 276 6 a a DT cord-014597-66vd2mdu 276 7 wide wide JJ cord-014597-66vd2mdu 276 8 range range NN cord-014597-66vd2mdu 276 9 of of IN cord-014597-66vd2mdu 276 10 . . . cord-014597-66vd2mdu 277 1 a a DT cord-014597-66vd2mdu 277 2 Schematic schematic JJ cord-014597-66vd2mdu 277 3 illustration illustration NN cord-014597-66vd2mdu 277 4 of of IN cord-014597-66vd2mdu 277 5 the the DT cord-014597-66vd2mdu 277 6 automated automate VBN cord-014597-66vd2mdu 277 7 cell cell NN cord-014597-66vd2mdu 277 8 culture culture NN cord-014597-66vd2mdu 277 9 system system NN cord-014597-66vd2mdu 277 10 . . . cord-014597-66vd2mdu 278 1 Only only RB cord-014597-66vd2mdu 278 2 the the DT cord-014597-66vd2mdu 278 3 core core NN cord-014597-66vd2mdu 278 4 system system NN cord-014597-66vd2mdu 278 5 is be VBZ cord-014597-66vd2mdu 278 6 shown show VBN cord-014597-66vd2mdu 278 7 with with IN cord-014597-66vd2mdu 278 8 a a DT cord-014597-66vd2mdu 278 9 robotic robotic JJ cord-014597-66vd2mdu 278 10 plate plate NN cord-014597-66vd2mdu 278 11 handler handler NN cord-014597-66vd2mdu 278 12 as as IN cord-014597-66vd2mdu 278 13 key key JJ cord-014597-66vd2mdu 278 14 device device NN cord-014597-66vd2mdu 278 15 connecting connect VBG cord-014597-66vd2mdu 278 16 cultivation cultivation NN cord-014597-66vd2mdu 278 17 , , , cord-014597-66vd2mdu 278 18 processing processing NN cord-014597-66vd2mdu 278 19 and and CC cord-014597-66vd2mdu 278 20 analytical analytical JJ cord-014597-66vd2mdu 278 21 parts part NNS cord-014597-66vd2mdu 278 22 . . . cord-014597-66vd2mdu 279 1 b b LS cord-014597-66vd2mdu 279 2 Illustration illustration NN cord-014597-66vd2mdu 279 3 of of IN cord-014597-66vd2mdu 279 4 an an DT cord-014597-66vd2mdu 279 5 example example NN cord-014597-66vd2mdu 279 6 how how WRB cord-014597-66vd2mdu 279 7 cell cell NN cord-014597-66vd2mdu 279 8 culture culture NN cord-014597-66vd2mdu 279 9 automation automation NN cord-014597-66vd2mdu 279 10 can can MD cord-014597-66vd2mdu 279 11 speed speed VB cord-014597-66vd2mdu 279 12 up up RP cord-014597-66vd2mdu 279 13 process process NN cord-014597-66vd2mdu 279 14 development development NN cord-014597-66vd2mdu 279 15 steps step NNS cord-014597-66vd2mdu 279 16 . . . cord-014597-66vd2mdu 280 1 c c NNP cord-014597-66vd2mdu 280 2 Application Application NNP cord-014597-66vd2mdu 280 3 in in IN cord-014597-66vd2mdu 280 4 the the DT cord-014597-66vd2mdu 280 5 identification identification NN cord-014597-66vd2mdu 280 6 of of IN cord-014597-66vd2mdu 280 7 product product NN cord-014597-66vd2mdu 280 8 quality quality NN cord-014597-66vd2mdu 280 9 levers lever NNS cord-014597-66vd2mdu 280 10 . . . cord-014597-66vd2mdu 281 1 d d NNP cord-014597-66vd2mdu 281 2 Application Application NNP cord-014597-66vd2mdu 281 3 in in IN cord-014597-66vd2mdu 281 4 titer titer NN cord-014597-66vd2mdu 281 5 optimization optimization NN cord-014597-66vd2mdu 281 6 biologic biologic NN cord-014597-66vd2mdu 281 7 molecules molecule NNS cord-014597-66vd2mdu 281 8 , , , cord-014597-66vd2mdu 281 9 including include VBG cord-014597-66vd2mdu 281 10 antibodies antibody NNS cord-014597-66vd2mdu 281 11 ( ( -LRB- cord-014597-66vd2mdu 281 12 IgGs IgGs NNP cord-014597-66vd2mdu 281 13 , , , cord-014597-66vd2mdu 281 14 novel novel JJ cord-014597-66vd2mdu 281 15 formats format NNS cord-014597-66vd2mdu 281 16 ) ) -RRB- cord-014597-66vd2mdu 281 17 and and CC cord-014597-66vd2mdu 281 18 other other JJ cord-014597-66vd2mdu 281 19 therapeutic therapeutic JJ cord-014597-66vd2mdu 281 20 proteins protein NNS cord-014597-66vd2mdu 281 21 ( ( -LRB- cord-014597-66vd2mdu 281 22 e.g. e.g. RB cord-014597-66vd2mdu 281 23 , , , cord-014597-66vd2mdu 281 24 fusion fusion NN cord-014597-66vd2mdu 281 25 proteins protein NNS cord-014597-66vd2mdu 281 26 ) ) -RRB- cord-014597-66vd2mdu 281 27 . . . cord-014597-66vd2mdu 282 1 Highlighted highlight VBN cord-014597-66vd2mdu 282 2 use use NN cord-014597-66vd2mdu 282 3 cases case NNS cord-014597-66vd2mdu 282 4 describe describe VBP cord-014597-66vd2mdu 282 5 the the DT cord-014597-66vd2mdu 282 6 identification identification NN cord-014597-66vd2mdu 282 7 of of IN cord-014597-66vd2mdu 282 8 top top JJ cord-014597-66vd2mdu 282 9 producer producer NN cord-014597-66vd2mdu 282 10 cell cell NN cord-014597-66vd2mdu 282 11 lines line NNS cord-014597-66vd2mdu 282 12 , , , cord-014597-66vd2mdu 282 13 decision decision NN cord-014597-66vd2mdu 282 14 making make VBG cord-014597-66vd2mdu 282 15 support support NN cord-014597-66vd2mdu 282 16 , , , cord-014597-66vd2mdu 282 17 bioreactor bioreactor NN cord-014597-66vd2mdu 282 18 data datum NNS cord-014597-66vd2mdu 282 19 management management NN cord-014597-66vd2mdu 282 20 , , , cord-014597-66vd2mdu 282 21 and and CC cord-014597-66vd2mdu 282 22 full full JJ cord-014597-66vd2mdu 282 23 clone clone NN cord-014597-66vd2mdu 282 24 history history NN cord-014597-66vd2mdu 282 25 report report NN cord-014597-66vd2mdu 282 26 documentation documentation NN cord-014597-66vd2mdu 282 27 ( ( -LRB- cord-014597-66vd2mdu 282 28 Fig Fig NNP cord-014597-66vd2mdu 282 29 . . . cord-014597-66vd2mdu 282 30 1 1 CD cord-014597-66vd2mdu 282 31 ) ) -RRB- cord-014597-66vd2mdu 282 32 . . . cord-014597-66vd2mdu 283 1 Genedata Genedata NNP cord-014597-66vd2mdu 283 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 283 3 , , , cord-014597-66vd2mdu 283 4 which which WDT cord-014597-66vd2mdu 283 5 was be VBD cord-014597-66vd2mdu 283 6 developed develop VBN cord-014597-66vd2mdu 283 7 in in IN cord-014597-66vd2mdu 283 8 collaboration collaboration NN cord-014597-66vd2mdu 283 9 with with IN cord-014597-66vd2mdu 283 10 top top JJ cord-014597-66vd2mdu 283 11 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 283 12 companies company NNS cord-014597-66vd2mdu 283 13 , , , cord-014597-66vd2mdu 283 14 can can MD cord-014597-66vd2mdu 283 15 flexibly flexibly RB cord-014597-66vd2mdu 283 16 support support VB cord-014597-66vd2mdu 283 17 various various JJ cord-014597-66vd2mdu 283 18 ( ( -LRB- cord-014597-66vd2mdu 283 19 non non JJ cord-014597-66vd2mdu 283 20 - - JJ cord-014597-66vd2mdu 283 21 linear linear JJ cord-014597-66vd2mdu 283 22 ) ) -RRB- cord-014597-66vd2mdu 283 23 workflows workflow NNS cord-014597-66vd2mdu 283 24 and and CC cord-014597-66vd2mdu 283 25 structure structure NN cord-014597-66vd2mdu 283 26 the the DT cord-014597-66vd2mdu 283 27 collected collect VBN cord-014597-66vd2mdu 283 28 information information NN cord-014597-66vd2mdu 283 29 in in IN cord-014597-66vd2mdu 283 30 a a DT cord-014597-66vd2mdu 283 31 way way NN cord-014597-66vd2mdu 283 32 that that WDT cord-014597-66vd2mdu 283 33 fosters foster VBZ cord-014597-66vd2mdu 283 34 collaboration collaboration NN cord-014597-66vd2mdu 283 35 across across IN cord-014597-66vd2mdu 283 36 an an DT cord-014597-66vd2mdu 283 37 organization organization NN cord-014597-66vd2mdu 283 38 . . . cord-014597-66vd2mdu 284 1 While while IN cord-014597-66vd2mdu 284 2 increasing increase VBG cord-014597-66vd2mdu 284 3 throughput throughput NN cord-014597-66vd2mdu 284 4 is be VBZ cord-014597-66vd2mdu 284 5 crucial crucial JJ cord-014597-66vd2mdu 284 6 to to TO cord-014597-66vd2mdu 284 7 ensure ensure VB cord-014597-66vd2mdu 284 8 the the DT cord-014597-66vd2mdu 284 9 timely timely JJ cord-014597-66vd2mdu 284 10 availability availability NN cord-014597-66vd2mdu 284 11 of of IN cord-014597-66vd2mdu 284 12 optimal optimal JJ cord-014597-66vd2mdu 284 13 producer producer NN cord-014597-66vd2mdu 284 14 cell cell NN cord-014597-66vd2mdu 284 15 lines line NNS cord-014597-66vd2mdu 284 16 , , , cord-014597-66vd2mdu 284 17 high high JJ cord-014597-66vd2mdu 284 18 - - HYPH cord-014597-66vd2mdu 284 19 throughput throughput NN cord-014597-66vd2mdu 284 20 is be VBZ cord-014597-66vd2mdu 284 21 only only RB cord-014597-66vd2mdu 284 22 possible possible JJ cord-014597-66vd2mdu 284 23 when when WRB cord-014597-66vd2mdu 284 24 automated automate VBN cord-014597-66vd2mdu 284 25 processes process NNS cord-014597-66vd2mdu 284 26 in in IN cord-014597-66vd2mdu 284 27 the the DT cord-014597-66vd2mdu 284 28 laboratory laboratory NN cord-014597-66vd2mdu 284 29 and and CC cord-014597-66vd2mdu 284 30 the the DT cord-014597-66vd2mdu 284 31 resulting result VBG cord-014597-66vd2mdu 284 32 data datum NNS cord-014597-66vd2mdu 284 33 collection collection NN cord-014597-66vd2mdu 284 34 and and CC cord-014597-66vd2mdu 284 35 aggregation aggregation NN cord-014597-66vd2mdu 284 36 can can MD cord-014597-66vd2mdu 284 37 be be VB cord-014597-66vd2mdu 284 38 streamlined streamline VBN cord-014597-66vd2mdu 284 39 . . . cord-014597-66vd2mdu 285 1 Genedata Genedata NNP cord-014597-66vd2mdu 285 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 285 3 helps help VBZ cord-014597-66vd2mdu 285 4 to to TO cord-014597-66vd2mdu 285 5 establish establish VB cord-014597-66vd2mdu 285 6 more more RBR cord-014597-66vd2mdu 285 7 productive productive JJ cord-014597-66vd2mdu 285 8 processes process NNS cord-014597-66vd2mdu 285 9 by by IN cord-014597-66vd2mdu 285 10 offering offer VBG cord-014597-66vd2mdu 285 11 support support NN cord-014597-66vd2mdu 285 12 and and CC cord-014597-66vd2mdu 285 13 integration integration NN cord-014597-66vd2mdu 285 14 for for IN cord-014597-66vd2mdu 285 15 automation automation NN cord-014597-66vd2mdu 285 16 stations station NNS cord-014597-66vd2mdu 285 17 and and CC cord-014597-66vd2mdu 285 18 measurement measurement NN cord-014597-66vd2mdu 285 19 devices device NNS cord-014597-66vd2mdu 285 20 . . . cord-014597-66vd2mdu 286 1 Thanks thank NNS cord-014597-66vd2mdu 286 2 to to IN cord-014597-66vd2mdu 286 3 the the DT cord-014597-66vd2mdu 286 4 comprehensive comprehensive JJ cord-014597-66vd2mdu 286 5 workflow workflow NN cord-014597-66vd2mdu 286 6 support support NN cord-014597-66vd2mdu 286 7 and and CC cord-014597-66vd2mdu 286 8 the the DT cord-014597-66vd2mdu 286 9 possibility possibility NN cord-014597-66vd2mdu 286 10 to to TO cord-014597-66vd2mdu 286 11 integrate integrate VB cord-014597-66vd2mdu 286 12 results result NNS cord-014597-66vd2mdu 286 13 from from IN cord-014597-66vd2mdu 286 14 cell cell NN cord-014597-66vd2mdu 286 15 line line NN cord-014597-66vd2mdu 286 16 stability stability NN cord-014597-66vd2mdu 286 17 experiments experiment NNS cord-014597-66vd2mdu 286 18 , , , cord-014597-66vd2mdu 286 19 product product NN cord-014597-66vd2mdu 286 20 quality quality NN cord-014597-66vd2mdu 286 21 assessment assessment NN cord-014597-66vd2mdu 286 22 , , , cord-014597-66vd2mdu 286 23 and and CC cord-014597-66vd2mdu 286 24 bioreactor bioreactor NN cord-014597-66vd2mdu 286 25 suitability suitability NN cord-014597-66vd2mdu 286 26 tests test NNS cord-014597-66vd2mdu 286 27 , , , cord-014597-66vd2mdu 286 28 Genedata Genedata NNP cord-014597-66vd2mdu 286 29 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 286 30 provides provide VBZ cord-014597-66vd2mdu 286 31 a a DT cord-014597-66vd2mdu 286 32 unique unique JJ cord-014597-66vd2mdu 286 33 way way NN cord-014597-66vd2mdu 286 34 to to TO cord-014597-66vd2mdu 286 35 evaluate evaluate VB cord-014597-66vd2mdu 286 36 cell cell NN cord-014597-66vd2mdu 286 37 lines line NNS cord-014597-66vd2mdu 286 38 . . . cord-014597-66vd2mdu 287 1 Comprehensive comprehensive JJ cord-014597-66vd2mdu 287 2 analysis analysis NN cord-014597-66vd2mdu 287 3 of of IN cord-014597-66vd2mdu 287 4 all all DT cord-014597-66vd2mdu 287 5 data datum NNS cord-014597-66vd2mdu 287 6 collected collect VBN cord-014597-66vd2mdu 287 7 in in IN cord-014597-66vd2mdu 287 8 the the DT cord-014597-66vd2mdu 287 9 process process NN cord-014597-66vd2mdu 287 10 helps help VBZ cord-014597-66vd2mdu 287 11 to to TO cord-014597-66vd2mdu 287 12 ensure ensure VB cord-014597-66vd2mdu 287 13 the the DT cord-014597-66vd2mdu 287 14 highest high JJS cord-014597-66vd2mdu 287 15 possible possible JJ cord-014597-66vd2mdu 287 16 quality quality NN cord-014597-66vd2mdu 287 17 and and CC cord-014597-66vd2mdu 287 18 minimize minimize VB cord-014597-66vd2mdu 287 19 the the DT cord-014597-66vd2mdu 287 20 time time NN cord-014597-66vd2mdu 287 21 and and CC cord-014597-66vd2mdu 287 22 resources resource NNS cord-014597-66vd2mdu 287 23 needed need VBN cord-014597-66vd2mdu 287 24 for for IN cord-014597-66vd2mdu 287 25 data datum NNS cord-014597-66vd2mdu 287 26 analysis analysis NN cord-014597-66vd2mdu 287 27 and and CC cord-014597-66vd2mdu 287 28 management management NN cord-014597-66vd2mdu 287 29 . . . cord-014597-66vd2mdu 288 1 Integration integration NN cord-014597-66vd2mdu 288 2 of of IN cord-014597-66vd2mdu 288 3 bioreactor bioreactor NN cord-014597-66vd2mdu 288 4 data datum NNS cord-014597-66vd2mdu 288 5 analysis analysis NN cord-014597-66vd2mdu 288 6 and and CC cord-014597-66vd2mdu 288 7 visualization visualization NN cord-014597-66vd2mdu 288 8 with with IN cord-014597-66vd2mdu 288 9 other other JJ cord-014597-66vd2mdu 288 10 parameters parameter NNS cord-014597-66vd2mdu 288 11 measured measure VBN cord-014597-66vd2mdu 288 12 in in IN cord-014597-66vd2mdu 288 13 cell cell NN cord-014597-66vd2mdu 288 14 line line NN cord-014597-66vd2mdu 288 15 development development NN cord-014597-66vd2mdu 288 16 , , , cord-014597-66vd2mdu 288 17 streamlines streamline VBZ cord-014597-66vd2mdu 288 18 clone clone NN cord-014597-66vd2mdu 288 19 evaluation evaluation NN cord-014597-66vd2mdu 288 20 in in IN cord-014597-66vd2mdu 288 21 micro micro NNS cord-014597-66vd2mdu 288 22 - - NNS cord-014597-66vd2mdu 288 23 bioreactors bioreactor NNS cord-014597-66vd2mdu 288 24 and and CC cord-014597-66vd2mdu 288 25 supports support VBZ cord-014597-66vd2mdu 288 26 highthroughput highthroughput NN cord-014597-66vd2mdu 288 27 operations operation NNS cord-014597-66vd2mdu 288 28 . . . cord-014597-66vd2mdu 289 1 Genedata Genedata NNP cord-014597-66vd2mdu 289 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 289 3 comprehensively comprehensively RB cord-014597-66vd2mdu 289 4 tracks track VBZ cord-014597-66vd2mdu 289 5 the the DT cord-014597-66vd2mdu 289 6 full full JJ cord-014597-66vd2mdu 289 7 clone clone NN cord-014597-66vd2mdu 289 8 history history NN cord-014597-66vd2mdu 289 9 from from IN cord-014597-66vd2mdu 289 10 the the DT cord-014597-66vd2mdu 289 11 origin origin NN cord-014597-66vd2mdu 289 12 of of IN cord-014597-66vd2mdu 289 13 the the DT cord-014597-66vd2mdu 289 14 host host NN cord-014597-66vd2mdu 289 15 cell cell NN cord-014597-66vd2mdu 289 16 line line NN cord-014597-66vd2mdu 289 17 to to IN cord-014597-66vd2mdu 289 18 the the DT cord-014597-66vd2mdu 289 19 generation generation NN cord-014597-66vd2mdu 289 20 of of IN cord-014597-66vd2mdu 289 21 the the DT cord-014597-66vd2mdu 289 22 validated validate VBN cord-014597-66vd2mdu 289 23 monoclonal monoclonal JJ cord-014597-66vd2mdu 289 24 producer producer NN cord-014597-66vd2mdu 289 25 cell cell NN cord-014597-66vd2mdu 289 26 line line NN cord-014597-66vd2mdu 289 27 . . . cord-014597-66vd2mdu 290 1 For for IN cord-014597-66vd2mdu 290 2 promising promising JJ cord-014597-66vd2mdu 290 3 clones clone NNS cord-014597-66vd2mdu 290 4 , , , cord-014597-66vd2mdu 290 5 the the DT cord-014597-66vd2mdu 290 6 clone clone NN cord-014597-66vd2mdu 290 7 history history NN cord-014597-66vd2mdu 290 8 report report NN cord-014597-66vd2mdu 290 9 can can MD cord-014597-66vd2mdu 290 10 be be VB cord-014597-66vd2mdu 290 11 generated generate VBN cord-014597-66vd2mdu 290 12 with with IN cord-014597-66vd2mdu 290 13 one one CD cord-014597-66vd2mdu 290 14 click click NN cord-014597-66vd2mdu 290 15 . . . cord-014597-66vd2mdu 291 1 Besides besides IN cord-014597-66vd2mdu 291 2 supporting support VBG cord-014597-66vd2mdu 291 3 cell cell NN cord-014597-66vd2mdu 291 4 line line NN cord-014597-66vd2mdu 291 5 development development NN cord-014597-66vd2mdu 291 6 , , , cord-014597-66vd2mdu 291 7 Genedata Genedata NNP cord-014597-66vd2mdu 291 8 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 291 9 is be VBZ cord-014597-66vd2mdu 291 10 a a DT cord-014597-66vd2mdu 291 11 comprehensive comprehensive JJ cord-014597-66vd2mdu 291 12 platform platform NN cord-014597-66vd2mdu 291 13 capable capable JJ cord-014597-66vd2mdu 291 14 of of IN cord-014597-66vd2mdu 291 15 tracking track VBG cord-014597-66vd2mdu 291 16 the the DT cord-014597-66vd2mdu 291 17 complete complete JJ cord-014597-66vd2mdu 291 18 bioprocess bioprocess NN cord-014597-66vd2mdu 291 19 development development NN cord-014597-66vd2mdu 291 20 process process NN cord-014597-66vd2mdu 291 21 . . . cord-014597-66vd2mdu 292 1 In in IN cord-014597-66vd2mdu 292 2 2012 2012 CD cord-014597-66vd2mdu 292 3 , , , cord-014597-66vd2mdu 292 4 14.1 14.1 CD cord-014597-66vd2mdu 292 5 million million CD cord-014597-66vd2mdu 292 6 people people NNS cord-014597-66vd2mdu 292 7 suffered suffer VBD cord-014597-66vd2mdu 292 8 from from IN cord-014597-66vd2mdu 292 9 cancer cancer NN cord-014597-66vd2mdu 292 10 [ [ -LRB- cord-014597-66vd2mdu 292 11 1 1 CD cord-014597-66vd2mdu 292 12 ] ] -RRB- cord-014597-66vd2mdu 292 13 making make VBG cord-014597-66vd2mdu 292 14 it -PRON- PRP cord-014597-66vd2mdu 292 15 to to IN cord-014597-66vd2mdu 292 16 a a DT cord-014597-66vd2mdu 292 17 major major JJ cord-014597-66vd2mdu 292 18 concern concern NN cord-014597-66vd2mdu 292 19 of of IN cord-014597-66vd2mdu 292 20 our -PRON- PRP$ cord-014597-66vd2mdu 292 21 society society NN cord-014597-66vd2mdu 292 22 . . . cord-014597-66vd2mdu 293 1 Since since IN cord-014597-66vd2mdu 293 2 common common JJ cord-014597-66vd2mdu 293 3 cancer cancer NN cord-014597-66vd2mdu 293 4 treatment treatment NN cord-014597-66vd2mdu 293 5 is be VBZ cord-014597-66vd2mdu 293 6 limited limit VBN cord-014597-66vd2mdu 293 7 and and CC cord-014597-66vd2mdu 293 8 not not RB cord-014597-66vd2mdu 293 9 effective effective JJ cord-014597-66vd2mdu 293 10 for for IN cord-014597-66vd2mdu 293 11 late late JJ cord-014597-66vd2mdu 293 12 stage stage NN cord-014597-66vd2mdu 293 13 carcinoma carcinoma NN cord-014597-66vd2mdu 293 14 , , , cord-014597-66vd2mdu 293 15 alternative alternative JJ cord-014597-66vd2mdu 293 16 methods method NNS cord-014597-66vd2mdu 293 17 are be VBP cord-014597-66vd2mdu 293 18 needed need VBN cord-014597-66vd2mdu 293 19 to to TO cord-014597-66vd2mdu 293 20 reduce reduce VB cord-014597-66vd2mdu 293 21 the the DT cord-014597-66vd2mdu 293 22 high high JJ cord-014597-66vd2mdu 293 23 mortality mortality NN cord-014597-66vd2mdu 293 24 rate rate NN cord-014597-66vd2mdu 293 25 of of IN cord-014597-66vd2mdu 293 26 cancer cancer NN cord-014597-66vd2mdu 293 27 patients patient NNS cord-014597-66vd2mdu 293 28 . . . cord-014597-66vd2mdu 294 1 One one CD cord-014597-66vd2mdu 294 2 alternative alternative JJ cord-014597-66vd2mdu 294 3 approach approach NN cord-014597-66vd2mdu 294 4 is be VBZ cord-014597-66vd2mdu 294 5 the the DT cord-014597-66vd2mdu 294 6 application application NN cord-014597-66vd2mdu 294 7 of of IN cord-014597-66vd2mdu 294 8 the the DT cord-014597-66vd2mdu 294 9 oncolytic oncolytic JJ cord-014597-66vd2mdu 294 10 Measles Measles NNP cord-014597-66vd2mdu 294 11 virus virus NN cord-014597-66vd2mdu 294 12 ( ( -LRB- cord-014597-66vd2mdu 294 13 OMV OMV NNP cord-014597-66vd2mdu 294 14 ) ) -RRB- cord-014597-66vd2mdu 294 15 , , , cord-014597-66vd2mdu 294 16 because because IN cord-014597-66vd2mdu 294 17 OMV OMV NNP cord-014597-66vd2mdu 294 18 has have VBZ cord-014597-66vd2mdu 294 19 a a DT cord-014597-66vd2mdu 294 20 natural natural JJ cord-014597-66vd2mdu 294 21 affinity affinity NN cord-014597-66vd2mdu 294 22 against against IN cord-014597-66vd2mdu 294 23 cancer cancer NN cord-014597-66vd2mdu 294 24 cells cell NNS cord-014597-66vd2mdu 294 25 . . . cord-014597-66vd2mdu 295 1 The the DT cord-014597-66vd2mdu 295 2 major major JJ cord-014597-66vd2mdu 295 3 drawbacks drawback NNS cord-014597-66vd2mdu 295 4 of of IN cord-014597-66vd2mdu 295 5 OMV OMV NNP cord-014597-66vd2mdu 295 6 is be VBZ cord-014597-66vd2mdu 295 7 to to TO cord-014597-66vd2mdu 295 8 produce produce VB cord-014597-66vd2mdu 295 9 the the DT cord-014597-66vd2mdu 295 10 extremely extremely RB cord-014597-66vd2mdu 295 11 high high JJ cord-014597-66vd2mdu 295 12 amount amount NN cord-014597-66vd2mdu 295 13 of of IN cord-014597-66vd2mdu 295 14 at at RB cord-014597-66vd2mdu 295 15 least least RBS cord-014597-66vd2mdu 295 16 10 10 CD cord-014597-66vd2mdu 295 17 11 11 CD cord-014597-66vd2mdu 295 18 TCID TCID NNP cord-014597-66vd2mdu 295 19 50 50 CD cord-014597-66vd2mdu 295 20 ( ( -LRB- cord-014597-66vd2mdu 295 21 50 50 CD cord-014597-66vd2mdu 295 22 % % NN cord-014597-66vd2mdu 295 23 tissue tissue NN cord-014597-66vd2mdu 295 24 culture culture NN cord-014597-66vd2mdu 295 25 infective infective JJ cord-014597-66vd2mdu 295 26 dose dose NN cord-014597-66vd2mdu 295 27 ) ) -RRB- cord-014597-66vd2mdu 295 28 per per IN cord-014597-66vd2mdu 295 29 dose dose NN cord-014597-66vd2mdu 295 30 [ [ -LRB- cord-014597-66vd2mdu 295 31 2 2 CD cord-014597-66vd2mdu 295 32 ] ] -RRB- cord-014597-66vd2mdu 295 33 which which WDT cord-014597-66vd2mdu 295 34 is be VBZ cord-014597-66vd2mdu 295 35 needed need VBN cord-014597-66vd2mdu 295 36 . . . cord-014597-66vd2mdu 296 1 To to TO cord-014597-66vd2mdu 296 2 solve solve VB cord-014597-66vd2mdu 296 3 this this DT cord-014597-66vd2mdu 296 4 problem problem NN cord-014597-66vd2mdu 296 5 , , , cord-014597-66vd2mdu 296 6 a a DT cord-014597-66vd2mdu 296 7 high high JJ cord-014597-66vd2mdu 296 8 titer titer NN cord-014597-66vd2mdu 296 9 process process NN cord-014597-66vd2mdu 296 10 must must MD cord-014597-66vd2mdu 296 11 be be VB cord-014597-66vd2mdu 296 12 established establish VBN cord-014597-66vd2mdu 296 13 including include VBG cord-014597-66vd2mdu 296 14 an an DT cord-014597-66vd2mdu 296 15 efficient efficient JJ cord-014597-66vd2mdu 296 16 downstream downstream JJ cord-014597-66vd2mdu 296 17 processing processing NN cord-014597-66vd2mdu 296 18 ( ( -LRB- cord-014597-66vd2mdu 296 19 DSP DSP NNP cord-014597-66vd2mdu 296 20 ) ) -RRB- cord-014597-66vd2mdu 296 21 . . . cord-014597-66vd2mdu 297 1 We -PRON- PRP cord-014597-66vd2mdu 297 2 developed develop VBD cord-014597-66vd2mdu 297 3 an an DT cord-014597-66vd2mdu 297 4 appropriate appropriate JJ cord-014597-66vd2mdu 297 5 upstream upstream JJ cord-014597-66vd2mdu 297 6 processing processing NN cord-014597-66vd2mdu 297 7 and and CC cord-014597-66vd2mdu 297 8 are be VBP cord-014597-66vd2mdu 297 9 able able JJ cord-014597-66vd2mdu 297 10 to to TO cord-014597-66vd2mdu 297 11 produce produce VB cord-014597-66vd2mdu 297 12 10 10 CD cord-014597-66vd2mdu 297 13 10 10 CD cord-014597-66vd2mdu 297 14 -10 -10 CD cord-014597-66vd2mdu 297 15 11 11 CD cord-014597-66vd2mdu 298 1 TCID TCID NNP cord-014597-66vd2mdu 298 2 50 50 CD cord-014597-66vd2mdu 298 3 mL ml NN cord-014597-66vd2mdu 299 1 -1 -1 . cord-014597-66vd2mdu 300 1 in in IN cord-014597-66vd2mdu 300 2 a a DT cord-014597-66vd2mdu 300 3 bioreactor bioreactor NN cord-014597-66vd2mdu 300 4 with with IN cord-014597-66vd2mdu 300 5 0.5 0.5 CD cord-014597-66vd2mdu 300 6 L l NN cord-014597-66vd2mdu 300 7 working working NN cord-014597-66vd2mdu 300 8 volume volume NN cord-014597-66vd2mdu 300 9 [ [ -LRB- cord-014597-66vd2mdu 300 10 3 3 CD cord-014597-66vd2mdu 300 11 ] ] -RRB- cord-014597-66vd2mdu 300 12 . . . cord-014597-66vd2mdu 301 1 Now now RB cord-014597-66vd2mdu 301 2 , , , cord-014597-66vd2mdu 301 3 we -PRON- PRP cord-014597-66vd2mdu 301 4 focus focus VBP cord-014597-66vd2mdu 301 5 on on IN cord-014597-66vd2mdu 301 6 the the DT cord-014597-66vd2mdu 301 7 DSP DSP NNP cord-014597-66vd2mdu 301 8 part part NN cord-014597-66vd2mdu 301 9 . . . cord-014597-66vd2mdu 302 1 The the DT cord-014597-66vd2mdu 302 2 following following JJ cord-014597-66vd2mdu 302 3 study study NN cord-014597-66vd2mdu 302 4 tested test VBD cord-014597-66vd2mdu 302 5 the the DT cord-014597-66vd2mdu 302 6 application application NN cord-014597-66vd2mdu 302 7 of of IN cord-014597-66vd2mdu 302 8 charged charge VBN cord-014597-66vd2mdu 302 9 depth depth NN cord-014597-66vd2mdu 302 10 filters filter NNS cord-014597-66vd2mdu 302 11 for for IN cord-014597-66vd2mdu 302 12 the the DT cord-014597-66vd2mdu 302 13 OMV OMV NNP cord-014597-66vd2mdu 302 14 clarification clarification NN cord-014597-66vd2mdu 302 15 . . . cord-014597-66vd2mdu 303 1 In in IN cord-014597-66vd2mdu 303 2 contrast contrast NN cord-014597-66vd2mdu 303 3 to to IN cord-014597-66vd2mdu 303 4 common common JJ cord-014597-66vd2mdu 303 5 DSP DSP NNP cord-014597-66vd2mdu 303 6 schemes scheme NNS cord-014597-66vd2mdu 303 7 , , , cord-014597-66vd2mdu 303 8 a a DT cord-014597-66vd2mdu 303 9 depletion depletion NN cord-014597-66vd2mdu 303 10 of of IN cord-014597-66vd2mdu 303 11 virus virus NN cord-014597-66vd2mdu 303 12 particles particle NNS cord-014597-66vd2mdu 303 13 or or CC cord-014597-66vd2mdu 303 14 a a DT cord-014597-66vd2mdu 303 15 loss loss NN cord-014597-66vd2mdu 303 16 of of IN cord-014597-66vd2mdu 303 17 infectivity infectivity NN cord-014597-66vd2mdu 303 18 is be VBZ cord-014597-66vd2mdu 303 19 not not RB cord-014597-66vd2mdu 303 20 desired desire VBN cord-014597-66vd2mdu 303 21 . . . cord-014597-66vd2mdu 304 1 The the DT cord-014597-66vd2mdu 304 2 aim aim NN cord-014597-66vd2mdu 304 3 is be VBZ cord-014597-66vd2mdu 304 4 a a DT cord-014597-66vd2mdu 304 5 reduction reduction NN cord-014597-66vd2mdu 304 6 of of IN cord-014597-66vd2mdu 304 7 protein protein NN cord-014597-66vd2mdu 304 8 content content NN cord-014597-66vd2mdu 304 9 and and CC cord-014597-66vd2mdu 304 10 DNA dna NN cord-014597-66vd2mdu 304 11 with with IN cord-014597-66vd2mdu 304 12 minimal minimal JJ cord-014597-66vd2mdu 304 13 loss loss NN cord-014597-66vd2mdu 304 14 of of IN cord-014597-66vd2mdu 304 15 infective infective JJ cord-014597-66vd2mdu 304 16 OMV omv NN cord-014597-66vd2mdu 304 17 . . . cord-014597-66vd2mdu 305 1 Further further RB cord-014597-66vd2mdu 305 2 , , , cord-014597-66vd2mdu 305 3 we -PRON- PRP cord-014597-66vd2mdu 305 4 investigated investigate VBD cord-014597-66vd2mdu 305 5 the the DT cord-014597-66vd2mdu 305 6 influence influence NN cord-014597-66vd2mdu 305 7 of of IN cord-014597-66vd2mdu 305 8 the the DT cord-014597-66vd2mdu 305 9 cell cell NN cord-014597-66vd2mdu 305 10 culture culture NN cord-014597-66vd2mdu 305 11 medium medium NN cord-014597-66vd2mdu 305 12 on on IN cord-014597-66vd2mdu 305 13 the the DT cord-014597-66vd2mdu 305 14 depth depth NN cord-014597-66vd2mdu 305 15 filtration filtration NN cord-014597-66vd2mdu 305 16 process process NN cord-014597-66vd2mdu 305 17 . . . cord-014597-66vd2mdu 306 1 To to TO cord-014597-66vd2mdu 306 2 explore explore VB cord-014597-66vd2mdu 306 3 the the DT cord-014597-66vd2mdu 306 4 influence influence NN cord-014597-66vd2mdu 306 5 of of IN cord-014597-66vd2mdu 306 6 the the DT cord-014597-66vd2mdu 306 7 surrounding surround VBG cord-014597-66vd2mdu 306 8 cell cell NN cord-014597-66vd2mdu 306 9 culture culture NN cord-014597-66vd2mdu 306 10 medium medium NN cord-014597-66vd2mdu 306 11 on on IN cord-014597-66vd2mdu 306 12 the the DT cord-014597-66vd2mdu 306 13 depth depth NN cord-014597-66vd2mdu 306 14 filtration filtration NN cord-014597-66vd2mdu 306 15 performance performance NN cord-014597-66vd2mdu 306 16 , , , cord-014597-66vd2mdu 306 17 OMV OMV NNP cord-014597-66vd2mdu 306 18 was be VBD cord-014597-66vd2mdu 306 19 either either CC cord-014597-66vd2mdu 306 20 produced produce VBN cord-014597-66vd2mdu 306 21 in in IN cord-014597-66vd2mdu 306 22 serum serum NN cord-014597-66vd2mdu 306 23 - - HYPH cord-014597-66vd2mdu 306 24 free free JJ cord-014597-66vd2mdu 306 25 medium medium NN cord-014597-66vd2mdu 306 26 ( ( -LRB- cord-014597-66vd2mdu 306 27 VP VP NNP cord-014597-66vd2mdu 306 28 - - HYPH cord-014597-66vd2mdu 306 29 SFM SFM NNP cord-014597-66vd2mdu 306 30 ) ) -RRB- cord-014597-66vd2mdu 306 31 or or CC cord-014597-66vd2mdu 306 32 serum serum NN cord-014597-66vd2mdu 306 33 - - HYPH cord-014597-66vd2mdu 306 34 containing contain VBG cord-014597-66vd2mdu 306 35 medium medium NN cord-014597-66vd2mdu 306 36 ( ( -LRB- cord-014597-66vd2mdu 306 37 DMEM DMEM NNP cord-014597-66vd2mdu 306 38 + + CC cord-014597-66vd2mdu 306 39 10 10 CD cord-014597-66vd2mdu 306 40 % % NN cord-014597-66vd2mdu 306 41 FCS FCS NNP cord-014597-66vd2mdu 306 42 ) ) -RRB- cord-014597-66vd2mdu 306 43 . . . cord-014597-66vd2mdu 307 1 The the DT cord-014597-66vd2mdu 307 2 production production NN cord-014597-66vd2mdu 307 3 was be VBD cord-014597-66vd2mdu 307 4 done do VBN cord-014597-66vd2mdu 307 5 in in IN cord-014597-66vd2mdu 307 6 a a DT cord-014597-66vd2mdu 307 7 STR str NN cord-014597-66vd2mdu 307 8 with with IN cord-014597-66vd2mdu 307 9 a a DT cord-014597-66vd2mdu 307 10 working working JJ cord-014597-66vd2mdu 307 11 volume volume NN cord-014597-66vd2mdu 307 12 of of IN cord-014597-66vd2mdu 307 13 0.5 0.5 CD cord-014597-66vd2mdu 307 14 L L NNP cord-014597-66vd2mdu 307 15 as as IN cord-014597-66vd2mdu 307 16 described describe VBN cord-014597-66vd2mdu 307 17 in in IN cord-014597-66vd2mdu 307 18 [ [ -LRB- cord-014597-66vd2mdu 307 19 3 3 CD cord-014597-66vd2mdu 307 20 ] ] -RRB- cord-014597-66vd2mdu 307 21 . . . cord-014597-66vd2mdu 308 1 Cells cell NNS cord-014597-66vd2mdu 308 2 and and CC cord-014597-66vd2mdu 308 3 carriers carrier NNS cord-014597-66vd2mdu 308 4 were be VBD cord-014597-66vd2mdu 308 5 separated separate VBN cord-014597-66vd2mdu 308 6 with with IN cord-014597-66vd2mdu 308 7 an an DT cord-014597-66vd2mdu 308 8 Opticap Opticap NNP cord-014597-66vd2mdu 308 9 XL XL NNP cord-014597-66vd2mdu 308 10 1-module 1-module CD cord-014597-66vd2mdu 309 1 ( ( -LRB- cord-014597-66vd2mdu 309 2 Polygard Polygard NNP cord-014597-66vd2mdu 309 3 - - HYPH cord-014597-66vd2mdu 309 4 CR CR NNP cord-014597-66vd2mdu 309 5 ; ; : cord-014597-66vd2mdu 309 6 5 5 CD cord-014597-66vd2mdu 309 7 μm μm NN cord-014597-66vd2mdu 309 8 ; ; : cord-014597-66vd2mdu 309 9 Merck Merck NNP cord-014597-66vd2mdu 309 10 ) ) -RRB- cord-014597-66vd2mdu 309 11 . . . cord-014597-66vd2mdu 310 1 For for IN cord-014597-66vd2mdu 310 2 the the DT cord-014597-66vd2mdu 310 3 depth depth NN cord-014597-66vd2mdu 310 4 filtration filtration NN cord-014597-66vd2mdu 310 5 Millistak+ millistak+ NN cord-014597-66vd2mdu 310 6 CE50 CE50 NNP cord-014597-66vd2mdu 310 7 filters filter NNS cord-014597-66vd2mdu 310 8 ( ( -LRB- cord-014597-66vd2mdu 310 9 Merck Merck NNP cord-014597-66vd2mdu 310 10 ) ) -RRB- cord-014597-66vd2mdu 310 11 were be VBD cord-014597-66vd2mdu 310 12 used use VBN cord-014597-66vd2mdu 310 13 . . . cord-014597-66vd2mdu 311 1 The the DT cord-014597-66vd2mdu 311 2 filter filter NN cord-014597-66vd2mdu 311 3 material material NN cord-014597-66vd2mdu 311 4 was be VBD cord-014597-66vd2mdu 311 5 autoclaved autoclave VBN cord-014597-66vd2mdu 311 6 and and CC cord-014597-66vd2mdu 311 7 rinsed rinse VBN cord-014597-66vd2mdu 311 8 with with IN cord-014597-66vd2mdu 311 9 25 25 CD cord-014597-66vd2mdu 311 10 mL mL NNS cord-014597-66vd2mdu 311 11 of of IN cord-014597-66vd2mdu 311 12 20 20 CD cord-014597-66vd2mdu 311 13 mM mM NNP cord-014597-66vd2mdu 311 14 Tris Tris NNP cord-014597-66vd2mdu 311 15 - - HYPH cord-014597-66vd2mdu 311 16 HCl HCl NNP cord-014597-66vd2mdu 311 17 ( ( -LRB- cord-014597-66vd2mdu 311 18 pH=7.4 pH=7.4 NNP cord-014597-66vd2mdu 311 19 ) ) -RRB- cord-014597-66vd2mdu 311 20 . . . cord-014597-66vd2mdu 312 1 The the DT cord-014597-66vd2mdu 312 2 virus virus NN cord-014597-66vd2mdu 312 3 suspension suspension NN cord-014597-66vd2mdu 312 4 was be VBD cord-014597-66vd2mdu 312 5 filtered filter VBN cord-014597-66vd2mdu 312 6 with with IN cord-014597-66vd2mdu 312 7 a a DT cord-014597-66vd2mdu 312 8 load load NN cord-014597-66vd2mdu 312 9 of of IN cord-014597-66vd2mdu 312 10 50 50 CD cord-014597-66vd2mdu 312 11 L l NN cord-014597-66vd2mdu 312 12 m m NN cord-014597-66vd2mdu 312 13 -2 -2 NNP cord-014597-66vd2mdu 312 14 using use VBG cord-014597-66vd2mdu 312 15 a a DT cord-014597-66vd2mdu 312 16 peristaltic peristaltic JJ cord-014597-66vd2mdu 312 17 pump pump NN cord-014597-66vd2mdu 312 18 ( ( -LRB- cord-014597-66vd2mdu 312 19 ISM931C ISM931C NNP cord-014597-66vd2mdu 312 20 ; ; : cord-014597-66vd2mdu 312 21 Ismatec Ismatec NNP cord-014597-66vd2mdu 312 22 ) ) -RRB- cord-014597-66vd2mdu 312 23 applying apply VBG cord-014597-66vd2mdu 312 24 a a DT cord-014597-66vd2mdu 312 25 flux flux NN cord-014597-66vd2mdu 312 26 of of IN cord-014597-66vd2mdu 312 27 150 150 CD cord-014597-66vd2mdu 312 28 L l NN cord-014597-66vd2mdu 312 29 m m NN cord-014597-66vd2mdu 312 30 -2 -2 NN cord-014597-66vd2mdu 312 31 h h NN cord-014597-66vd2mdu 312 32 -1 -1 NN cord-014597-66vd2mdu 313 1 ( ( -LRB- cord-014597-66vd2mdu 313 2 Fig Fig NNP cord-014597-66vd2mdu 313 3 . . NNP cord-014597-66vd2mdu 313 4 1 1 CD cord-014597-66vd2mdu 313 5 ) ) -RRB- cord-014597-66vd2mdu 313 6 . . . cord-014597-66vd2mdu 314 1 Samples sample NNS cord-014597-66vd2mdu 314 2 were be VBD cord-014597-66vd2mdu 314 3 collected collect VBN cord-014597-66vd2mdu 314 4 at at IN cord-014597-66vd2mdu 314 5 the the DT cord-014597-66vd2mdu 314 6 beginning beginning NN cord-014597-66vd2mdu 314 7 and and CC cord-014597-66vd2mdu 314 8 end end NN cord-014597-66vd2mdu 314 9 of of IN cord-014597-66vd2mdu 314 10 a a DT cord-014597-66vd2mdu 314 11 filtration filtration NN cord-014597-66vd2mdu 314 12 run run NN cord-014597-66vd2mdu 314 13 . . . cord-014597-66vd2mdu 315 1 The the DT cord-014597-66vd2mdu 315 2 OMV OMV NNP cord-014597-66vd2mdu 315 3 titer titer NN cord-014597-66vd2mdu 315 4 ( ( -LRB- cord-014597-66vd2mdu 315 5 TCID TCID NNP cord-014597-66vd2mdu 315 6 50 50 CD cord-014597-66vd2mdu 315 7 mL ml NN cord-014597-66vd2mdu 315 8 -1 -1 NN cord-014597-66vd2mdu 315 9 ) ) -RRB- cord-014597-66vd2mdu 315 10 of of IN cord-014597-66vd2mdu 315 11 the the DT cord-014597-66vd2mdu 315 12 samples sample NNS cord-014597-66vd2mdu 315 13 was be VBD cord-014597-66vd2mdu 315 14 determined determine VBN cord-014597-66vd2mdu 315 15 according accord VBG cord-014597-66vd2mdu 315 16 to to IN cord-014597-66vd2mdu 315 17 Kärber Kärber NNP cord-014597-66vd2mdu 315 18 and and CC cord-014597-66vd2mdu 315 19 Reed Reed NNP cord-014597-66vd2mdu 315 20 [ [ -LRB- cord-014597-66vd2mdu 315 21 4 4 CD cord-014597-66vd2mdu 315 22 , , , cord-014597-66vd2mdu 315 23 5 5 CD cord-014597-66vd2mdu 315 24 ] ] -RRB- cord-014597-66vd2mdu 315 25 . . . cord-014597-66vd2mdu 316 1 Protein protein NN cord-014597-66vd2mdu 316 2 content content NN cord-014597-66vd2mdu 316 3 was be VBD cord-014597-66vd2mdu 316 4 measured measure VBN cord-014597-66vd2mdu 316 5 with with IN cord-014597-66vd2mdu 316 6 the the DT cord-014597-66vd2mdu 316 7 Pierce Pierce NNP cord-014597-66vd2mdu 316 8 BCA BCA NNP cord-014597-66vd2mdu 316 9 protein protein NN cord-014597-66vd2mdu 316 10 assay assay NN cord-014597-66vd2mdu 316 11 kit kit NN cord-014597-66vd2mdu 316 12 ( ( -LRB- cord-014597-66vd2mdu 316 13 ThermoFisher ThermoFisher NNP cord-014597-66vd2mdu 316 14 Scientific Scientific NNP cord-014597-66vd2mdu 316 15 ) ) -RRB- cord-014597-66vd2mdu 316 16 according accord VBG cord-014597-66vd2mdu 316 17 to to IN cord-014597-66vd2mdu 316 18 the the DT cord-014597-66vd2mdu 316 19 manufacturer manufacturer NN cord-014597-66vd2mdu 316 20 's 's POS cord-014597-66vd2mdu 316 21 instructions instruction NNS cord-014597-66vd2mdu 316 22 . . . cord-014597-66vd2mdu 317 1 DNA DNA NNP cord-014597-66vd2mdu 317 2 was be VBD cord-014597-66vd2mdu 317 3 measured measure VBN cord-014597-66vd2mdu 317 4 by by IN cord-014597-66vd2mdu 317 5 a a DT cord-014597-66vd2mdu 317 6 microtiter microtiter NN cord-014597-66vd2mdu 317 7 assay assay NN cord-014597-66vd2mdu 317 8 using use VBG cord-014597-66vd2mdu 317 9 Quant Quant NNP cord-014597-66vd2mdu 317 10 - - : cord-014597-66vd2mdu 317 11 iT it PRP cord-014597-66vd2mdu 317 12 PicoGreen PicoGreen NNP cord-014597-66vd2mdu 317 13 dsDNA dsdna RB cord-014597-66vd2mdu 317 14 reagent reagent NN cord-014597-66vd2mdu 317 15 ( ( -LRB- cord-014597-66vd2mdu 317 16 ThermoFisher ThermoFisher NNP cord-014597-66vd2mdu 317 17 Scientific Scientific NNP cord-014597-66vd2mdu 317 18 ) ) -RRB- cord-014597-66vd2mdu 317 19 according accord VBG cord-014597-66vd2mdu 317 20 to to IN cord-014597-66vd2mdu 317 21 the the DT cord-014597-66vd2mdu 317 22 manufacturer manufacturer NN cord-014597-66vd2mdu 317 23 's 's POS cord-014597-66vd2mdu 317 24 instructions instruction NNS cord-014597-66vd2mdu 317 25 . . . cord-014597-66vd2mdu 318 1 We -PRON- PRP cord-014597-66vd2mdu 318 2 found find VBD cord-014597-66vd2mdu 318 3 that that IN cord-014597-66vd2mdu 318 4 positively positively RB cord-014597-66vd2mdu 318 5 charged charge VBN cord-014597-66vd2mdu 318 6 depth depth NN cord-014597-66vd2mdu 318 7 filters filter NNS cord-014597-66vd2mdu 318 8 were be VBD cord-014597-66vd2mdu 318 9 suitable suitable JJ cord-014597-66vd2mdu 318 10 to to TO cord-014597-66vd2mdu 318 11 clarify clarify VB cord-014597-66vd2mdu 318 12 OMV omv NN cord-014597-66vd2mdu 318 13 suspensions suspension NNS cord-014597-66vd2mdu 318 14 . . . cord-014597-66vd2mdu 319 1 The the DT cord-014597-66vd2mdu 319 2 cell cell NN cord-014597-66vd2mdu 319 3 culture culture NN cord-014597-66vd2mdu 319 4 medium medium NN cord-014597-66vd2mdu 319 5 , , , cord-014597-66vd2mdu 319 6 in in IN cord-014597-66vd2mdu 319 7 which which WDT cord-014597-66vd2mdu 319 8 the the DT cord-014597-66vd2mdu 319 9 OMV OMV NNP cord-014597-66vd2mdu 319 10 was be VBD cord-014597-66vd2mdu 319 11 produced produce VBN cord-014597-66vd2mdu 319 12 , , , cord-014597-66vd2mdu 319 13 influenced influence VBD cord-014597-66vd2mdu 319 14 the the DT cord-014597-66vd2mdu 319 15 outcome outcome NN cord-014597-66vd2mdu 319 16 of of IN cord-014597-66vd2mdu 319 17 the the DT cord-014597-66vd2mdu 319 18 depth depth NN cord-014597-66vd2mdu 319 19 filtration filtration NN cord-014597-66vd2mdu 319 20 . . . cord-014597-66vd2mdu 320 1 A a DT cord-014597-66vd2mdu 320 2 log log NN cord-014597-66vd2mdu 320 3 reduction reduction NN cord-014597-66vd2mdu 320 4 value value NN cord-014597-66vd2mdu 320 5 ( ( -LRB- cord-014597-66vd2mdu 320 6 LRV lrv NN cord-014597-66vd2mdu 320 7 ) ) -RRB- cord-014597-66vd2mdu 320 8 of of IN cord-014597-66vd2mdu 320 9 0.87 0.87 CD cord-014597-66vd2mdu 320 10 was be VBD cord-014597-66vd2mdu 320 11 determined determine VBN cord-014597-66vd2mdu 320 12 for for IN cord-014597-66vd2mdu 320 13 OMV omv NN cord-014597-66vd2mdu 320 14 present present JJ cord-014597-66vd2mdu 320 15 in in IN cord-014597-66vd2mdu 320 16 serum serum NN cord-014597-66vd2mdu 320 17 - - HYPH cord-014597-66vd2mdu 320 18 containing contain VBG cord-014597-66vd2mdu 320 19 medium medium NN cord-014597-66vd2mdu 320 20 ( ( -LRB- cord-014597-66vd2mdu 320 21 SCM SCM NNP cord-014597-66vd2mdu 320 22 ) ) -RRB- cord-014597-66vd2mdu 320 23 , , , cord-014597-66vd2mdu 320 24 whereas whereas IN cord-014597-66vd2mdu 320 25 the the DT cord-014597-66vd2mdu 320 26 titer titer NN cord-014597-66vd2mdu 320 27 of of IN cord-014597-66vd2mdu 320 28 OMV OMV NNP cord-014597-66vd2mdu 320 29 in in IN cord-014597-66vd2mdu 320 30 serumfree serumfree JJ cord-014597-66vd2mdu 320 31 medium medium NN cord-014597-66vd2mdu 320 32 ( ( -LRB- cord-014597-66vd2mdu 320 33 SFM SFM NNP cord-014597-66vd2mdu 320 34 ) ) -RRB- cord-014597-66vd2mdu 320 35 was be VBD cord-014597-66vd2mdu 320 36 reduced reduce VBN cord-014597-66vd2mdu 320 37 1.63 1.63 CD cord-014597-66vd2mdu 320 38 log log NN cord-014597-66vd2mdu 320 39 levels level NNS cord-014597-66vd2mdu 320 40 . . . cord-014597-66vd2mdu 321 1 This this DT cord-014597-66vd2mdu 321 2 indicates indicate VBZ cord-014597-66vd2mdu 321 3 that that IN cord-014597-66vd2mdu 321 4 without without IN cord-014597-66vd2mdu 321 5 serum serum NN cord-014597-66vd2mdu 321 6 in in IN cord-014597-66vd2mdu 321 7 the the DT cord-014597-66vd2mdu 321 8 surrounding surround VBG cord-014597-66vd2mdu 321 9 liquid liquid NN cord-014597-66vd2mdu 321 10 , , , cord-014597-66vd2mdu 321 11 OMV OMV NNP cord-014597-66vd2mdu 321 12 will will MD cord-014597-66vd2mdu 321 13 adsorb adsorb VB cord-014597-66vd2mdu 321 14 to to IN cord-014597-66vd2mdu 321 15 the the DT cord-014597-66vd2mdu 321 16 filter filter NN cord-014597-66vd2mdu 321 17 material material NN cord-014597-66vd2mdu 321 18 . . . cord-014597-66vd2mdu 322 1 However however RB cord-014597-66vd2mdu 322 2 , , , cord-014597-66vd2mdu 322 3 we -PRON- PRP cord-014597-66vd2mdu 322 4 must must MD cord-014597-66vd2mdu 322 5 evaluate evaluate VB cord-014597-66vd2mdu 322 6 if if IN cord-014597-66vd2mdu 322 7 the the DT cord-014597-66vd2mdu 322 8 missing miss VBG cord-014597-66vd2mdu 322 9 serum serum NN cord-014597-66vd2mdu 322 10 or or CC cord-014597-66vd2mdu 322 11 other other JJ cord-014597-66vd2mdu 322 12 components component NNS cord-014597-66vd2mdu 322 13 present present JJ cord-014597-66vd2mdu 322 14 in in IN cord-014597-66vd2mdu 322 15 SFM SFM NNP cord-014597-66vd2mdu 322 16 are be VBP cord-014597-66vd2mdu 322 17 responsible responsible JJ cord-014597-66vd2mdu 322 18 for for IN cord-014597-66vd2mdu 322 19 this this DT cord-014597-66vd2mdu 322 20 effect effect NN cord-014597-66vd2mdu 322 21 . . . cord-014597-66vd2mdu 323 1 Total total JJ cord-014597-66vd2mdu 323 2 protein protein NN cord-014597-66vd2mdu 323 3 was be VBD cord-014597-66vd2mdu 323 4 not not RB cord-014597-66vd2mdu 323 5 relevantly relevantly RB cord-014597-66vd2mdu 323 6 reduced reduce VBN cord-014597-66vd2mdu 323 7 by by IN cord-014597-66vd2mdu 323 8 the the DT cord-014597-66vd2mdu 323 9 clarification clarification NN cord-014597-66vd2mdu 323 10 using use VBG cord-014597-66vd2mdu 323 11 charged charge VBN cord-014597-66vd2mdu 323 12 depth depth NN cord-014597-66vd2mdu 323 13 filters filter NNS cord-014597-66vd2mdu 323 14 . . . cord-014597-66vd2mdu 324 1 For for IN cord-014597-66vd2mdu 324 2 OMV OMV NNP cord-014597-66vd2mdu 324 3 present present JJ cord-014597-66vd2mdu 324 4 in in IN cord-014597-66vd2mdu 324 5 SCM SCM NNP cord-014597-66vd2mdu 324 6 , , , cord-014597-66vd2mdu 324 7 the the DT cord-014597-66vd2mdu 324 8 residual residual JJ cord-014597-66vd2mdu 324 9 protein protein NN cord-014597-66vd2mdu 324 10 content content NN cord-014597-66vd2mdu 324 11 was be VBD cord-014597-66vd2mdu 324 12 slightly slightly RB cord-014597-66vd2mdu 324 13 less less RBR cord-014597-66vd2mdu 324 14 compared compare VBN cord-014597-66vd2mdu 324 15 to to IN cord-014597-66vd2mdu 324 16 OMV omv NN cord-014597-66vd2mdu 324 17 present present JJ cord-014597-66vd2mdu 324 18 in in IN cord-014597-66vd2mdu 324 19 SFM SFM NNP cord-014597-66vd2mdu 324 20 ( ( -LRB- cord-014597-66vd2mdu 324 21 Table table NN cord-014597-66vd2mdu 324 22 1 1 CD cord-014597-66vd2mdu 324 23 ) ) -RRB- cord-014597-66vd2mdu 324 24 . . . cord-014597-66vd2mdu 325 1 In in IN cord-014597-66vd2mdu 325 2 contrast contrast NN cord-014597-66vd2mdu 325 3 , , , cord-014597-66vd2mdu 325 4 host host NN cord-014597-66vd2mdu 325 5 cell cell NN cord-014597-66vd2mdu 325 6 DNA dna NN cord-014597-66vd2mdu 325 7 ( ( -LRB- cord-014597-66vd2mdu 325 8 hcDNA hcdna RB cord-014597-66vd2mdu 325 9 ) ) -RRB- cord-014597-66vd2mdu 325 10 was be VBD cord-014597-66vd2mdu 325 11 bound bind VBN cord-014597-66vd2mdu 325 12 to to IN cord-014597-66vd2mdu 325 13 the the DT cord-014597-66vd2mdu 325 14 filter filter NN cord-014597-66vd2mdu 325 15 material material NN cord-014597-66vd2mdu 325 16 . . . cord-014597-66vd2mdu 326 1 We -PRON- PRP cord-014597-66vd2mdu 326 2 achieved achieve VBD cord-014597-66vd2mdu 326 3 a a DT cord-014597-66vd2mdu 326 4 33 33 CD cord-014597-66vd2mdu 326 5 % % NN cord-014597-66vd2mdu 326 6 reduction reduction NN cord-014597-66vd2mdu 326 7 of of IN cord-014597-66vd2mdu 326 8 hcDNA hcdna NN cord-014597-66vd2mdu 326 9 for for IN cord-014597-66vd2mdu 326 10 an an DT cord-014597-66vd2mdu 326 11 OMV OMV NNP cord-014597-66vd2mdu 326 12 suspension suspension NN cord-014597-66vd2mdu 326 13 in in IN cord-014597-66vd2mdu 326 14 SFM SFM NNP cord-014597-66vd2mdu 326 15 . . . cord-014597-66vd2mdu 327 1 After after IN cord-014597-66vd2mdu 327 2 clarifying clarify VBG cord-014597-66vd2mdu 327 3 an an DT cord-014597-66vd2mdu 327 4 OMV omv NN cord-014597-66vd2mdu 327 5 suspension suspension NN cord-014597-66vd2mdu 327 6 in in IN cord-014597-66vd2mdu 327 7 SFM SFM NNP cord-014597-66vd2mdu 327 8 , , , cord-014597-66vd2mdu 327 9 the the DT cord-014597-66vd2mdu 327 10 remaining remain VBG cord-014597-66vd2mdu 327 11 hcDNA hcdna JJ cord-014597-66vd2mdu 327 12 content content NN cord-014597-66vd2mdu 327 13 was be VBD cord-014597-66vd2mdu 327 14 even even RB cord-014597-66vd2mdu 327 15 lower low JJR cord-014597-66vd2mdu 327 16 being be VBG cord-014597-66vd2mdu 327 17 only only RB cord-014597-66vd2mdu 327 18 42 42 CD cord-014597-66vd2mdu 327 19 % % NN cord-014597-66vd2mdu 327 20 . . . cord-014597-66vd2mdu 328 1 Conclusions conclusion NNS cord-014597-66vd2mdu 328 2 Charged charge VBN cord-014597-66vd2mdu 328 3 depth depth NN cord-014597-66vd2mdu 328 4 filters filter NNS cord-014597-66vd2mdu 328 5 are be VBP cord-014597-66vd2mdu 328 6 suitable suitable JJ cord-014597-66vd2mdu 328 7 for for IN cord-014597-66vd2mdu 328 8 the the DT cord-014597-66vd2mdu 328 9 first first JJ cord-014597-66vd2mdu 328 10 clarification clarification NN cord-014597-66vd2mdu 328 11 step step NN cord-014597-66vd2mdu 328 12 of of IN cord-014597-66vd2mdu 328 13 OMV OMV NNP cord-014597-66vd2mdu 328 14 downstream downstream JJ cord-014597-66vd2mdu 328 15 processing processing NN cord-014597-66vd2mdu 328 16 . . . cord-014597-66vd2mdu 329 1 Residual residual JJ cord-014597-66vd2mdu 329 2 protein protein NN cord-014597-66vd2mdu 329 3 could could MD cord-014597-66vd2mdu 329 4 pass pass VB cord-014597-66vd2mdu 329 5 the the DT cord-014597-66vd2mdu 329 6 depth depth NN cord-014597-66vd2mdu 329 7 Scheme scheme NN cord-014597-66vd2mdu 329 8 of of IN cord-014597-66vd2mdu 329 9 the the DT cord-014597-66vd2mdu 329 10 complete complete JJ cord-014597-66vd2mdu 329 11 cell cell NN cord-014597-66vd2mdu 329 12 line line NN cord-014597-66vd2mdu 329 13 development development NN cord-014597-66vd2mdu 329 14 workflow workflow NN cord-014597-66vd2mdu 329 15 support support NN cord-014597-66vd2mdu 329 16 in in IN cord-014597-66vd2mdu 329 17 Genedata Genedata NNP cord-014597-66vd2mdu 329 18 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 329 19 . . . cord-014597-66vd2mdu 330 1 Showcasing showcase VBG cord-014597-66vd2mdu 330 2 integration integration NN cord-014597-66vd2mdu 330 3 of of IN cord-014597-66vd2mdu 330 4 data datum NNS cord-014597-66vd2mdu 330 5 from from IN cord-014597-66vd2mdu 330 6 diverse diverse JJ cord-014597-66vd2mdu 330 7 measurement measurement NN cord-014597-66vd2mdu 330 8 instruments instrument NNS cord-014597-66vd2mdu 330 9 , , , cord-014597-66vd2mdu 330 10 data datum NNS cord-014597-66vd2mdu 330 11 visualization visualization NN cord-014597-66vd2mdu 330 12 for for IN cord-014597-66vd2mdu 330 13 decision decision NN cord-014597-66vd2mdu 330 14 making make VBG cord-014597-66vd2mdu 330 15 support support NN cord-014597-66vd2mdu 330 16 as as RB cord-014597-66vd2mdu 330 17 well well RB cord-014597-66vd2mdu 330 18 as as IN cord-014597-66vd2mdu 330 19 , , , cord-014597-66vd2mdu 330 20 tracking tracking NN cord-014597-66vd2mdu 330 21 of of IN cord-014597-66vd2mdu 330 22 full full JJ cord-014597-66vd2mdu 330 23 clone clone NN cord-014597-66vd2mdu 330 24 history history NN cord-014597-66vd2mdu 330 25 filter filter NN cord-014597-66vd2mdu 330 26 almost almost RB cord-014597-66vd2mdu 330 27 unhindered unhindered JJ cord-014597-66vd2mdu 330 28 , , , cord-014597-66vd2mdu 330 29 whereas whereas IN cord-014597-66vd2mdu 330 30 the the DT cord-014597-66vd2mdu 330 31 hcDNA hcdna JJ cord-014597-66vd2mdu 330 32 content content NN cord-014597-66vd2mdu 330 33 was be VBD cord-014597-66vd2mdu 330 34 already already RB cord-014597-66vd2mdu 330 35 reduced reduce VBN cord-014597-66vd2mdu 330 36 to to IN cord-014597-66vd2mdu 330 37 42 42 CD cord-014597-66vd2mdu 330 38 % % NN cord-014597-66vd2mdu 330 39 at at IN cord-014597-66vd2mdu 330 40 maximum maximum NN cord-014597-66vd2mdu 330 41 . . . cord-014597-66vd2mdu 331 1 However however RB cord-014597-66vd2mdu 331 2 , , , cord-014597-66vd2mdu 331 3 the the DT cord-014597-66vd2mdu 331 4 OMV OMV NNP cord-014597-66vd2mdu 331 5 titer titer NN cord-014597-66vd2mdu 331 6 was be VBD cord-014597-66vd2mdu 331 7 also also RB cord-014597-66vd2mdu 331 8 reduced reduce VBN cord-014597-66vd2mdu 331 9 by by IN cord-014597-66vd2mdu 331 10 the the DT cord-014597-66vd2mdu 331 11 depth depth NN cord-014597-66vd2mdu 331 12 filtration filtration NN cord-014597-66vd2mdu 331 13 . . . cord-014597-66vd2mdu 332 1 This this DT cord-014597-66vd2mdu 332 2 undesired undesired JJ cord-014597-66vd2mdu 332 3 effect effect NN cord-014597-66vd2mdu 332 4 was be VBD cord-014597-66vd2mdu 332 5 stronger strong JJR cord-014597-66vd2mdu 332 6 for for IN cord-014597-66vd2mdu 332 7 the the DT cord-014597-66vd2mdu 332 8 OMV OMV NNP cord-014597-66vd2mdu 332 9 present present NN cord-014597-66vd2mdu 332 10 in in IN cord-014597-66vd2mdu 332 11 SFM SFM NNP cord-014597-66vd2mdu 332 12 . . . cord-014597-66vd2mdu 333 1 Because because IN cord-014597-66vd2mdu 333 2 the the DT cord-014597-66vd2mdu 333 3 agencies agency NNS cord-014597-66vd2mdu 333 4 require require VBP cord-014597-66vd2mdu 333 5 avoiding avoid VBG cord-014597-66vd2mdu 333 6 serum serum NN cord-014597-66vd2mdu 333 7 in in IN cord-014597-66vd2mdu 333 8 clinical clinical JJ cord-014597-66vd2mdu 333 9 - - HYPH cord-014597-66vd2mdu 333 10 grade grade NN cord-014597-66vd2mdu 333 11 production production NN cord-014597-66vd2mdu 333 12 processes process NNS cord-014597-66vd2mdu 333 13 , , , cord-014597-66vd2mdu 333 14 this this DT cord-014597-66vd2mdu 333 15 is be VBZ cord-014597-66vd2mdu 333 16 disadvantageous disadvantageous JJ cord-014597-66vd2mdu 333 17 . . . cord-014597-66vd2mdu 334 1 Nonetheless nonetheless RB cord-014597-66vd2mdu 334 2 , , , cord-014597-66vd2mdu 334 3 because because IN cord-014597-66vd2mdu 334 4 SFM SFM NNP cord-014597-66vd2mdu 334 5 will will MD cord-014597-66vd2mdu 334 6 be be VB cord-014597-66vd2mdu 334 7 soon soon RB cord-014597-66vd2mdu 334 8 standard standard JJ cord-014597-66vd2mdu 334 9 for for IN cord-014597-66vd2mdu 334 10 OMV OMV NNP cord-014597-66vd2mdu 334 11 production production NN cord-014597-66vd2mdu 334 12 , , , cord-014597-66vd2mdu 334 13 further further JJ cord-014597-66vd2mdu 334 14 experiments experiment NNS cord-014597-66vd2mdu 334 15 have have VBP cord-014597-66vd2mdu 334 16 to to TO cord-014597-66vd2mdu 334 17 be be VB cord-014597-66vd2mdu 334 18 done do VBN cord-014597-66vd2mdu 334 19 preventing prevent VBG cord-014597-66vd2mdu 334 20 the the DT cord-014597-66vd2mdu 334 21 OMV OMV NNP cord-014597-66vd2mdu 334 22 reduction reduction NN cord-014597-66vd2mdu 334 23 during during IN cord-014597-66vd2mdu 334 24 clarification clarification NN cord-014597-66vd2mdu 334 25 . . . cord-014597-66vd2mdu 335 1 One one CD cord-014597-66vd2mdu 335 2 option option NN cord-014597-66vd2mdu 335 3 can can MD cord-014597-66vd2mdu 335 4 be be VB cord-014597-66vd2mdu 335 5 to to TO cord-014597-66vd2mdu 335 6 reduce reduce VB cord-014597-66vd2mdu 335 7 the the DT cord-014597-66vd2mdu 335 8 adsorption adsorption NN cord-014597-66vd2mdu 335 9 strength strength NN cord-014597-66vd2mdu 335 10 of of IN cord-014597-66vd2mdu 335 11 the the DT cord-014597-66vd2mdu 335 12 virus virus NN cord-014597-66vd2mdu 335 13 to to IN cord-014597-66vd2mdu 335 14 the the DT cord-014597-66vd2mdu 335 15 filter filter NN cord-014597-66vd2mdu 335 16 material material NN cord-014597-66vd2mdu 335 17 by by IN cord-014597-66vd2mdu 335 18 the the DT cord-014597-66vd2mdu 335 19 addition addition NN cord-014597-66vd2mdu 335 20 of of IN cord-014597-66vd2mdu 335 21 salt salt NN cord-014597-66vd2mdu 335 22 . . . cord-014597-66vd2mdu 336 1 Moreover moreover RB cord-014597-66vd2mdu 336 2 , , , cord-014597-66vd2mdu 336 3 it -PRON- PRP cord-014597-66vd2mdu 336 4 is be VBZ cord-014597-66vd2mdu 336 5 important important JJ cord-014597-66vd2mdu 336 6 to to TO cord-014597-66vd2mdu 336 7 establish establish VB cord-014597-66vd2mdu 336 8 a a DT cord-014597-66vd2mdu 336 9 standardized standardized JJ cord-014597-66vd2mdu 336 10 protocol protocol NN cord-014597-66vd2mdu 336 11 for for IN cord-014597-66vd2mdu 336 12 the the DT cord-014597-66vd2mdu 336 13 upstream upstream JJ cord-014597-66vd2mdu 336 14 processing processing NN cord-014597-66vd2mdu 336 15 . . . cord-014597-66vd2mdu 337 1 We -PRON- PRP cord-014597-66vd2mdu 337 2 determined determine VBD cord-014597-66vd2mdu 337 3 batch batch NN cord-014597-66vd2mdu 337 4 - - HYPH cord-014597-66vd2mdu 337 5 to to IN cord-014597-66vd2mdu 337 6 - - HYPH cord-014597-66vd2mdu 337 7 batch batch NN cord-014597-66vd2mdu 337 8 variations variation NNS cord-014597-66vd2mdu 337 9 within within IN cord-014597-66vd2mdu 337 10 the the DT cord-014597-66vd2mdu 337 11 clarification clarification NN cord-014597-66vd2mdu 337 12 indicating indicate VBG cord-014597-66vd2mdu 337 13 a a DT cord-014597-66vd2mdu 337 14 strong strong JJ cord-014597-66vd2mdu 337 15 impact impact NN cord-014597-66vd2mdu 337 16 of of IN cord-014597-66vd2mdu 337 17 upstream upstream JJ cord-014597-66vd2mdu 337 18 processing processing NN cord-014597-66vd2mdu 337 19 ( ( -LRB- cord-014597-66vd2mdu 337 20 USP USP NNP cord-014597-66vd2mdu 337 21 ) ) -RRB- cord-014597-66vd2mdu 337 22 on on IN cord-014597-66vd2mdu 337 23 the the DT cord-014597-66vd2mdu 337 24 outcome outcome NN cord-014597-66vd2mdu 337 25 of of IN cord-014597-66vd2mdu 337 26 the the DT cord-014597-66vd2mdu 337 27 DSP DSP NNP cord-014597-66vd2mdu 337 28 . . . cord-014597-66vd2mdu 338 1 Therefore therefore RB cord-014597-66vd2mdu 338 2 , , , cord-014597-66vd2mdu 338 3 further further JJ cord-014597-66vd2mdu 338 4 studies study NNS cord-014597-66vd2mdu 338 5 must must MD cord-014597-66vd2mdu 338 6 investigate investigate VB cord-014597-66vd2mdu 338 7 the the DT cord-014597-66vd2mdu 338 8 influence influence NN cord-014597-66vd2mdu 338 9 of of IN cord-014597-66vd2mdu 338 10 USP USP NNP cord-014597-66vd2mdu 338 11 parameter parameter NN cord-014597-66vd2mdu 338 12 e.g. e.g. IN cord-014597-66vd2mdu 338 13 time time NN cord-014597-66vd2mdu 338 14 of of IN cord-014597-66vd2mdu 338 15 harvest harvest NN cord-014597-66vd2mdu 338 16 and and CC cord-014597-66vd2mdu 338 17 pH ph NN cord-014597-66vd2mdu 338 18 of of IN cord-014597-66vd2mdu 338 19 the the DT cord-014597-66vd2mdu 338 20 harvest harvest NN cord-014597-66vd2mdu 338 21 solution solution NN cord-014597-66vd2mdu 338 22 on on IN cord-014597-66vd2mdu 338 23 the the DT cord-014597-66vd2mdu 338 24 OMV OMV NNP cord-014597-66vd2mdu 338 25 . . . cord-014597-66vd2mdu 339 1 Fed Fed NNP cord-014597-66vd2mdu 339 2 - - HYPH cord-014597-66vd2mdu 339 3 batch batch NN cord-014597-66vd2mdu 339 4 culture culture NN cord-014597-66vd2mdu 339 5 is be VBZ cord-014597-66vd2mdu 339 6 commonly commonly RB cord-014597-66vd2mdu 339 7 employed employ VBN cord-014597-66vd2mdu 339 8 to to TO cord-014597-66vd2mdu 339 9 maximize maximize VB cord-014597-66vd2mdu 339 10 cell cell NN cord-014597-66vd2mdu 339 11 and and CC cord-014597-66vd2mdu 339 12 product product NN cord-014597-66vd2mdu 339 13 concentrations concentration NNS cord-014597-66vd2mdu 339 14 in in IN cord-014597-66vd2mdu 339 15 upstream upstream JJ cord-014597-66vd2mdu 339 16 mammalian mammalian JJ cord-014597-66vd2mdu 339 17 cell cell NN cord-014597-66vd2mdu 339 18 culture culture NN cord-014597-66vd2mdu 339 19 processes process NNS cord-014597-66vd2mdu 339 20 . . . cord-014597-66vd2mdu 340 1 Typical typical JJ cord-014597-66vd2mdu 340 2 standard standard JJ cord-014597-66vd2mdu 340 3 platform platform NN cord-014597-66vd2mdu 340 4 processes process NNS cord-014597-66vd2mdu 340 5 rely rely VBP cord-014597-66vd2mdu 340 6 on on IN cord-014597-66vd2mdu 340 7 fixed fix VBN cord-014597-66vd2mdu 340 8 - - HYPH cord-014597-66vd2mdu 340 9 volume volume NN cord-014597-66vd2mdu 340 10 bolus bolus NN cord-014597-66vd2mdu 340 11 feeding feeding NN cord-014597-66vd2mdu 340 12 of of IN cord-014597-66vd2mdu 340 13 concentrated concentrated JJ cord-014597-66vd2mdu 340 14 feed feed NN cord-014597-66vd2mdu 340 15 supplements supplement NNS cord-014597-66vd2mdu 340 16 at at IN cord-014597-66vd2mdu 340 17 regular regular JJ cord-014597-66vd2mdu 340 18 intervals interval NNS cord-014597-66vd2mdu 340 19 . . . cord-014597-66vd2mdu 341 1 However however RB cord-014597-66vd2mdu 341 2 , , , cord-014597-66vd2mdu 341 3 such such JJ cord-014597-66vd2mdu 341 4 static static JJ cord-014597-66vd2mdu 341 5 approaches approach NNS cord-014597-66vd2mdu 341 6 might may MD cord-014597-66vd2mdu 341 7 result result VB cord-014597-66vd2mdu 341 8 in in IN cord-014597-66vd2mdu 341 9 over over IN cord-014597-66vd2mdu 341 10 - - HYPH cord-014597-66vd2mdu 341 11 or or CC cord-014597-66vd2mdu 341 12 underfeeding underfeeding NN cord-014597-66vd2mdu 341 13 . . . cord-014597-66vd2mdu 342 1 To to TO cord-014597-66vd2mdu 342 2 mimic mimic VB cord-014597-66vd2mdu 342 3 more more RBR cord-014597-66vd2mdu 342 4 closely closely RB cord-014597-66vd2mdu 342 5 the the DT cord-014597-66vd2mdu 342 6 dynamics dynamic NNS cord-014597-66vd2mdu 342 7 of of IN cord-014597-66vd2mdu 342 8 a a DT cord-014597-66vd2mdu 342 9 fed feed VBN cord-014597-66vd2mdu 342 10 - - HYPH cord-014597-66vd2mdu 342 11 batch batch NN cord-014597-66vd2mdu 342 12 culture culture NN cord-014597-66vd2mdu 342 13 , , , cord-014597-66vd2mdu 342 14 we -PRON- PRP cord-014597-66vd2mdu 342 15 developed develop VBD cord-014597-66vd2mdu 342 16 a a DT cord-014597-66vd2mdu 342 17 dynamic dynamic JJ cord-014597-66vd2mdu 342 18 feeding feeding NN cord-014597-66vd2mdu 342 19 strategy strategy NN cord-014597-66vd2mdu 342 20 responsive responsive JJ cord-014597-66vd2mdu 342 21 to to IN cord-014597-66vd2mdu 342 22 the the DT cord-014597-66vd2mdu 342 23 actual actual JJ cord-014597-66vd2mdu 342 24 nutrient nutrient NN cord-014597-66vd2mdu 342 25 needs need NNS cord-014597-66vd2mdu 342 26 of of IN cord-014597-66vd2mdu 342 27 a a DT cord-014597-66vd2mdu 342 28 mAb mab NN cord-014597-66vd2mdu 342 29 - - HYPH cord-014597-66vd2mdu 342 30 producing produce VBG cord-014597-66vd2mdu 342 31 recombinant recombinant JJ cord-014597-66vd2mdu 342 32 CHO CHO NNP cord-014597-66vd2mdu 342 33 cell cell NN cord-014597-66vd2mdu 342 34 line line NN cord-014597-66vd2mdu 342 35 . . . cord-014597-66vd2mdu 343 1 Results result NNS cord-014597-66vd2mdu 343 2 and and CC cord-014597-66vd2mdu 343 3 discussion discussion NN cord-014597-66vd2mdu 343 4 Improvements improvement NNS cord-014597-66vd2mdu 343 5 made make VBN cord-014597-66vd2mdu 343 6 at at IN cord-014597-66vd2mdu 343 7 different different JJ cord-014597-66vd2mdu 343 8 steps step NNS cord-014597-66vd2mdu 343 9 during during IN cord-014597-66vd2mdu 343 10 fed fed NNP cord-014597-66vd2mdu 343 11 - - HYPH cord-014597-66vd2mdu 343 12 batch batch NN cord-014597-66vd2mdu 343 13 development development NN cord-014597-66vd2mdu 343 14 are be VBP cord-014597-66vd2mdu 343 15 shown show VBN cord-014597-66vd2mdu 343 16 in in IN cord-014597-66vd2mdu 343 17 Fig Fig NNP cord-014597-66vd2mdu 343 18 . . . cord-014597-66vd2mdu 344 1 1 1 LS cord-014597-66vd2mdu 344 2 . . . cord-014597-66vd2mdu 345 1 At at IN cord-014597-66vd2mdu 345 2 step step NN cord-014597-66vd2mdu 345 3 1 1 CD cord-014597-66vd2mdu 345 4 , , , cord-014597-66vd2mdu 345 5 all all DT cord-014597-66vd2mdu 345 6 eight eight CD cord-014597-66vd2mdu 345 7 Cell cell NN cord-014597-66vd2mdu 345 8 Boost boost NN cord-014597-66vd2mdu 345 9 supplements supplement NNS cord-014597-66vd2mdu 345 10 were be VBD cord-014597-66vd2mdu 345 11 added add VBN cord-014597-66vd2mdu 345 12 to to IN cord-014597-66vd2mdu 345 13 CDM4NS0 cdm4ns0 NN cord-014597-66vd2mdu 345 14 according accord VBG cord-014597-66vd2mdu 345 15 to to IN cord-014597-66vd2mdu 345 16 a a DT cord-014597-66vd2mdu 345 17 DoE doe NN cord-014597-66vd2mdu 345 18 approach approach NN cord-014597-66vd2mdu 345 19 , , , cord-014597-66vd2mdu 345 20 and and CC cord-014597-66vd2mdu 345 21 batch batch NN cord-014597-66vd2mdu 345 22 cultures culture NNS cord-014597-66vd2mdu 345 23 were be VBD cord-014597-66vd2mdu 345 24 performed perform VBN cord-014597-66vd2mdu 345 25 . . . cord-014597-66vd2mdu 346 1 This this DT cord-014597-66vd2mdu 346 2 evaluation evaluation NN cord-014597-66vd2mdu 346 3 allowed allow VBD cord-014597-66vd2mdu 346 4 us -PRON- PRP cord-014597-66vd2mdu 346 5 to to TO cord-014597-66vd2mdu 346 6 select select VB cord-014597-66vd2mdu 346 7 only only RB cord-014597-66vd2mdu 346 8 those those DT cord-014597-66vd2mdu 346 9 Cell cell NN cord-014597-66vd2mdu 346 10 Boost boost NN cord-014597-66vd2mdu 346 11 supplements supplement NNS cord-014597-66vd2mdu 346 12 that that WDT cord-014597-66vd2mdu 346 13 were be VBD cord-014597-66vd2mdu 346 14 beneficial beneficial JJ cord-014597-66vd2mdu 346 15 to to IN cord-014597-66vd2mdu 346 16 the the DT cord-014597-66vd2mdu 346 17 overall overall JJ cord-014597-66vd2mdu 346 18 culture culture NN cord-014597-66vd2mdu 346 19 performance performance NN cord-014597-66vd2mdu 346 20 . . . cord-014597-66vd2mdu 347 1 Non non JJ cord-014597-66vd2mdu 347 2 - - JJ cord-014597-66vd2mdu 347 3 performing perform VBG cord-014597-66vd2mdu 347 4 Cell cell NN cord-014597-66vd2mdu 347 5 Boost boost NN cord-014597-66vd2mdu 347 6 supplements supplement NNS cord-014597-66vd2mdu 347 7 were be VBD cord-014597-66vd2mdu 347 8 removed remove VBN cord-014597-66vd2mdu 347 9 and and CC cord-014597-66vd2mdu 347 10 not not RB cord-014597-66vd2mdu 347 11 considered consider VBN cord-014597-66vd2mdu 347 12 further far RBR cord-014597-66vd2mdu 347 13 . . . cord-014597-66vd2mdu 348 1 At at IN cord-014597-66vd2mdu 348 2 step step NN cord-014597-66vd2mdu 348 3 2 2 CD cord-014597-66vd2mdu 348 4 , , , cord-014597-66vd2mdu 348 5 the the DT cord-014597-66vd2mdu 348 6 selected select VBN cord-014597-66vd2mdu 348 7 Cell Cell NNP cord-014597-66vd2mdu 348 8 Boost Boost NNP cord-014597-66vd2mdu 348 9 supplements supplement NNS cord-014597-66vd2mdu 348 10 were be VBD cord-014597-66vd2mdu 348 11 added add VBN cord-014597-66vd2mdu 348 12 daily daily RB cord-014597-66vd2mdu 348 13 to to IN cord-014597-66vd2mdu 348 14 the the DT cord-014597-66vd2mdu 348 15 cultures culture NNS cord-014597-66vd2mdu 348 16 at at IN cord-014597-66vd2mdu 348 17 different different JJ cord-014597-66vd2mdu 348 18 ratios ratio NNS cord-014597-66vd2mdu 348 19 according accord VBG cord-014597-66vd2mdu 348 20 to to IN cord-014597-66vd2mdu 348 21 a a DT cord-014597-66vd2mdu 348 22 DoE doe NN cord-014597-66vd2mdu 348 23 approach approach NN cord-014597-66vd2mdu 348 24 , , , cord-014597-66vd2mdu 348 25 and and CC cord-014597-66vd2mdu 348 26 fedbatch fedbatch NN cord-014597-66vd2mdu 348 27 cultures culture NNS cord-014597-66vd2mdu 348 28 were be VBD cord-014597-66vd2mdu 348 29 conducted conduct VBN cord-014597-66vd2mdu 348 30 . . . cord-014597-66vd2mdu 349 1 As as IN cord-014597-66vd2mdu 349 2 expected expect VBN cord-014597-66vd2mdu 349 3 , , , cord-014597-66vd2mdu 349 4 daily daily JJ cord-014597-66vd2mdu 349 5 feed feed NN cord-014597-66vd2mdu 349 6 additions addition NNS cord-014597-66vd2mdu 349 7 to to TO cord-014597-66vd2mdu 349 8 replenish replenish VB cord-014597-66vd2mdu 349 9 consumed consume VBN cord-014597-66vd2mdu 349 10 nutrients nutrient NNS cord-014597-66vd2mdu 349 11 substantially substantially RB cord-014597-66vd2mdu 349 12 improved improve VBN cord-014597-66vd2mdu 349 13 mAb mab NN cord-014597-66vd2mdu 349 14 and and CC cord-014597-66vd2mdu 349 15 peak peak NN cord-014597-66vd2mdu 349 16 cell cell NN cord-014597-66vd2mdu 349 17 concentrations concentration NNS cord-014597-66vd2mdu 349 18 as as RB cord-014597-66vd2mdu 349 19 well well RB cord-014597-66vd2mdu 349 20 as as IN cord-014597-66vd2mdu 349 21 viable viable JJ cord-014597-66vd2mdu 349 22 cumulative cumulative JJ cord-014597-66vd2mdu 349 23 cell cell NN cord-014597-66vd2mdu 349 24 days day NNS cord-014597-66vd2mdu 349 25 ( ( -LRB- cord-014597-66vd2mdu 349 26 VCCD VCCD NNP cord-014597-66vd2mdu 349 27 ) ) -RRB- cord-014597-66vd2mdu 349 28 compared compare VBN cord-014597-66vd2mdu 349 29 to to IN cord-014597-66vd2mdu 349 30 batch batch VB cord-014597-66vd2mdu 349 31 cultivation cultivation NN cord-014597-66vd2mdu 349 32 . . . cord-014597-66vd2mdu 350 1 Further further RB cord-014597-66vd2mdu 350 2 , , , cord-014597-66vd2mdu 350 3 the the DT cord-014597-66vd2mdu 350 4 results result NNS cord-014597-66vd2mdu 350 5 enabled enable VBD cord-014597-66vd2mdu 350 6 us -PRON- PRP cord-014597-66vd2mdu 350 7 to to IN cord-014597-66vd2mdu 350 8 fine fine JJ cord-014597-66vd2mdu 350 9 - - HYPH cord-014597-66vd2mdu 350 10 tune tune VB cord-014597-66vd2mdu 350 11 the the DT cord-014597-66vd2mdu 350 12 feed feed NN cord-014597-66vd2mdu 350 13 ratio ratio NN cord-014597-66vd2mdu 350 14 of of IN cord-014597-66vd2mdu 350 15 selected select VBN cord-014597-66vd2mdu 350 16 Cell Cell NNP cord-014597-66vd2mdu 350 17 Boost Boost NNP cord-014597-66vd2mdu 350 18 supplements supplement NNS cord-014597-66vd2mdu 350 19 . . . cord-014597-66vd2mdu 351 1 At at IN cord-014597-66vd2mdu 351 2 step step NN cord-014597-66vd2mdu 351 3 3 3 CD cord-014597-66vd2mdu 351 4 , , , cord-014597-66vd2mdu 351 5 we -PRON- PRP cord-014597-66vd2mdu 351 6 further further RB cord-014597-66vd2mdu 351 7 optimized optimize VBD cord-014597-66vd2mdu 351 8 the the DT cord-014597-66vd2mdu 351 9 best good JJS cord-014597-66vd2mdu 351 10 performing perform VBG cord-014597-66vd2mdu 351 11 feed feed NN cord-014597-66vd2mdu 351 12 ratio ratio NN cord-014597-66vd2mdu 351 13 by by IN cord-014597-66vd2mdu 351 14 investigation investigation NN cord-014597-66vd2mdu 351 15 of of IN cord-014597-66vd2mdu 351 16 static static JJ cord-014597-66vd2mdu 351 17 and and CC cord-014597-66vd2mdu 351 18 dynamic dynamic JJ cord-014597-66vd2mdu 351 19 feed feed NN cord-014597-66vd2mdu 351 20 protocols protocol NNS cord-014597-66vd2mdu 351 21 . . . cord-014597-66vd2mdu 352 1 Most Most JJS cord-014597-66vd2mdu 352 2 fed fed JJ cord-014597-66vd2mdu 352 3 - - HYPH cord-014597-66vd2mdu 352 4 batch batch NN cord-014597-66vd2mdu 352 5 protocols protocol NNS cord-014597-66vd2mdu 352 6 rely rely VBP cord-014597-66vd2mdu 352 7 on on IN cord-014597-66vd2mdu 352 8 constant constant JJ cord-014597-66vd2mdu 352 9 feed feed NN cord-014597-66vd2mdu 352 10 additions addition NNS cord-014597-66vd2mdu 352 11 on on IN cord-014597-66vd2mdu 352 12 distinct distinct JJ cord-014597-66vd2mdu 352 13 days day NNS cord-014597-66vd2mdu 352 14 . . . cord-014597-66vd2mdu 353 1 However however RB cord-014597-66vd2mdu 353 2 , , , cord-014597-66vd2mdu 353 3 these these DT cord-014597-66vd2mdu 353 4 approaches approach NNS cord-014597-66vd2mdu 353 5 often often RB cord-014597-66vd2mdu 353 6 lead lead VBP cord-014597-66vd2mdu 353 7 to to IN cord-014597-66vd2mdu 353 8 substantial substantial JJ cord-014597-66vd2mdu 353 9 over over RB cord-014597-66vd2mdu 353 10 - - HYPH cord-014597-66vd2mdu 353 11 or or CC cord-014597-66vd2mdu 353 12 underfeeding underfeede VBG cord-014597-66vd2mdu 353 13 during during IN cord-014597-66vd2mdu 353 14 bioprocessing bioprocessing NN cord-014597-66vd2mdu 353 15 . . . cord-014597-66vd2mdu 354 1 To to TO cord-014597-66vd2mdu 354 2 improve improve VB cord-014597-66vd2mdu 354 3 such such JJ cord-014597-66vd2mdu 354 4 " " `` cord-014597-66vd2mdu 354 5 static static JJ cord-014597-66vd2mdu 354 6 " " '' cord-014597-66vd2mdu 354 7 protocols protocol NNS cord-014597-66vd2mdu 354 8 , , , cord-014597-66vd2mdu 354 9 we -PRON- PRP cord-014597-66vd2mdu 354 10 investigated investigate VBD cord-014597-66vd2mdu 354 11 three three CD cord-014597-66vd2mdu 354 12 different different JJ cord-014597-66vd2mdu 354 13 " " `` cord-014597-66vd2mdu 354 14 dynamic dynamic JJ cord-014597-66vd2mdu 354 15 " " '' cord-014597-66vd2mdu 354 16 approaches approach NNS cord-014597-66vd2mdu 354 17 as as IN cord-014597-66vd2mdu 354 18 shown show VBN cord-014597-66vd2mdu 354 19 in in IN cord-014597-66vd2mdu 354 20 Table Table NNP cord-014597-66vd2mdu 354 21 1 1 CD cord-014597-66vd2mdu 354 22 by by IN cord-014597-66vd2mdu 354 23 applying apply VBG cord-014597-66vd2mdu 354 24 the the DT cord-014597-66vd2mdu 354 25 selected select VBN cord-014597-66vd2mdu 354 26 Cell Cell NNP cord-014597-66vd2mdu 354 27 Boost Boost NNP cord-014597-66vd2mdu 354 28 supplements supplement NNS cord-014597-66vd2mdu 354 29 with with IN cord-014597-66vd2mdu 354 30 the the DT cord-014597-66vd2mdu 354 31 optimized optimize VBN cord-014597-66vd2mdu 354 32 feed feed NN cord-014597-66vd2mdu 354 33 ratio ratio NN cord-014597-66vd2mdu 354 34 . . . cord-014597-66vd2mdu 355 1 This this DT cord-014597-66vd2mdu 355 2 investigation investigation NN cord-014597-66vd2mdu 355 3 allowed allow VBD cord-014597-66vd2mdu 355 4 us -PRON- PRP cord-014597-66vd2mdu 355 5 to to TO cord-014597-66vd2mdu 355 6 further further RB cord-014597-66vd2mdu 355 7 improve improve VB cord-014597-66vd2mdu 355 8 the the DT cord-014597-66vd2mdu 355 9 bioprocess bioprocess NN cord-014597-66vd2mdu 355 10 performance performance NN cord-014597-66vd2mdu 355 11 . . . cord-014597-66vd2mdu 356 1 The the DT cord-014597-66vd2mdu 356 2 best good JJS cord-014597-66vd2mdu 356 3 performing perform VBG cord-014597-66vd2mdu 356 4 approaches approach NNS cord-014597-66vd2mdu 356 5 , , , cord-014597-66vd2mdu 356 6 constant constant JJ cord-014597-66vd2mdu 356 7 and and CC cord-014597-66vd2mdu 356 8 retrospective retrospective JJ cord-014597-66vd2mdu 356 9 feed feed NN cord-014597-66vd2mdu 356 10 , , , cord-014597-66vd2mdu 356 11 were be VBD cord-014597-66vd2mdu 356 12 further further RB cord-014597-66vd2mdu 356 13 investigated investigate VBN cord-014597-66vd2mdu 356 14 in in IN cord-014597-66vd2mdu 356 15 fully fully RB cord-014597-66vd2mdu 356 16 automated automate VBN cord-014597-66vd2mdu 356 17 bioreactors bioreactor NNS cord-014597-66vd2mdu 356 18 under under IN cord-014597-66vd2mdu 356 19 controlled control VBN cord-014597-66vd2mdu 356 20 conditions condition NNS cord-014597-66vd2mdu 356 21 . . . cord-014597-66vd2mdu 357 1 In in IN cord-014597-66vd2mdu 357 2 general general JJ cord-014597-66vd2mdu 357 3 , , , cord-014597-66vd2mdu 357 4 constant constant JJ cord-014597-66vd2mdu 357 5 cultivation cultivation NN cord-014597-66vd2mdu 357 6 parameters parameter NNS cord-014597-66vd2mdu 357 7 in in IN cord-014597-66vd2mdu 357 8 the the DT cord-014597-66vd2mdu 357 9 bioreactor bioreactor NN cord-014597-66vd2mdu 357 10 slightly slightly RB cord-014597-66vd2mdu 357 11 enhanced enhance VBN cord-014597-66vd2mdu 357 12 mAb mAb NNS cord-014597-66vd2mdu 357 13 titers titer NNS cord-014597-66vd2mdu 357 14 compared compare VBN cord-014597-66vd2mdu 357 15 to to TO cord-014597-66vd2mdu 357 16 shake shake VB cord-014597-66vd2mdu 357 17 flask flask NN cord-014597-66vd2mdu 357 18 cultivation cultivation NN cord-014597-66vd2mdu 357 19 . . . cord-014597-66vd2mdu 358 1 The the DT cord-014597-66vd2mdu 358 2 retrospective retrospective JJ cord-014597-66vd2mdu 358 3 feed feed NN cord-014597-66vd2mdu 358 4 strategy strategy NN cord-014597-66vd2mdu 358 5 yielded yield VBD cord-014597-66vd2mdu 358 6 10 10 CD cord-014597-66vd2mdu 358 7 % % NN cord-014597-66vd2mdu 358 8 higher high JJR cord-014597-66vd2mdu 358 9 titers titer NNS cord-014597-66vd2mdu 358 10 than than IN cord-014597-66vd2mdu 358 11 the the DT cord-014597-66vd2mdu 358 12 constant constant JJ cord-014597-66vd2mdu 358 13 strategy strategy NN cord-014597-66vd2mdu 358 14 . . . cord-014597-66vd2mdu 359 1 Overall overall RB cord-014597-66vd2mdu 359 2 , , , cord-014597-66vd2mdu 359 3 the the DT cord-014597-66vd2mdu 359 4 established establish VBN cord-014597-66vd2mdu 359 5 methodology methodology NN cord-014597-66vd2mdu 359 6 for for IN cord-014597-66vd2mdu 359 7 fed fed JJ cord-014597-66vd2mdu 359 8 - - HYPH cord-014597-66vd2mdu 359 9 batch batch NN cord-014597-66vd2mdu 359 10 development development NN cord-014597-66vd2mdu 359 11 allowed allow VBD cord-014597-66vd2mdu 359 12 us -PRON- PRP cord-014597-66vd2mdu 359 13 to to TO cord-014597-66vd2mdu 359 14 obtain obtain VB cord-014597-66vd2mdu 359 15 2.5× 2.5× CD cord-014597-66vd2mdu 359 16 higher high JJR cord-014597-66vd2mdu 359 17 mAb mAb NNS cord-014597-66vd2mdu 359 18 titers titer NNS cord-014597-66vd2mdu 359 19 ( ( -LRB- cord-014597-66vd2mdu 359 20 batch batch JJ cord-014597-66vd2mdu 359 21 mean mean NN cord-014597-66vd2mdu 359 22 : : : cord-014597-66vd2mdu 359 23 1.9 1.9 CD cord-014597-66vd2mdu 359 24 g g NN cord-014597-66vd2mdu 359 25 / / SYM cord-014597-66vd2mdu 359 26 L l NN cord-014597-66vd2mdu 359 27 vs. vs. FW cord-014597-66vd2mdu 359 28 fed fed JJ cord-014597-66vd2mdu 359 29 - - HYPH cord-014597-66vd2mdu 359 30 batch batch NN cord-014597-66vd2mdu 359 31 4.9 4.9 CD cord-014597-66vd2mdu 359 32 g g NN cord-014597-66vd2mdu 359 33 / / SYM cord-014597-66vd2mdu 359 34 L L NNP cord-014597-66vd2mdu 359 35 ) ) -RRB- cord-014597-66vd2mdu 359 36 in in IN cord-014597-66vd2mdu 359 37 a a DT cord-014597-66vd2mdu 359 38 short short JJ cord-014597-66vd2mdu 359 39 time time NN cord-014597-66vd2mdu 359 40 and and CC cord-014597-66vd2mdu 359 41 three three CD cord-014597-66vd2mdu 359 42 simple simple JJ cord-014597-66vd2mdu 359 43 steps step NNS cord-014597-66vd2mdu 359 44 . . . cord-014597-66vd2mdu 360 1 In in IN cord-014597-66vd2mdu 360 2 addition addition NN cord-014597-66vd2mdu 360 3 , , , cord-014597-66vd2mdu 360 4 the the DT cord-014597-66vd2mdu 360 5 product product NN cord-014597-66vd2mdu 360 6 quality quality NN cord-014597-66vd2mdu 360 7 was be VBD cord-014597-66vd2mdu 360 8 investigated investigate VBN cord-014597-66vd2mdu 360 9 . . . cord-014597-66vd2mdu 361 1 Compared compare VBN cord-014597-66vd2mdu 361 2 to to IN cord-014597-66vd2mdu 361 3 the the DT cord-014597-66vd2mdu 361 4 legacy legacy NN cord-014597-66vd2mdu 361 5 fedbatch fedbatch NN cord-014597-66vd2mdu 361 6 process process NN cord-014597-66vd2mdu 361 7 , , , cord-014597-66vd2mdu 361 8 fed fed NNP cord-014597-66vd2mdu 361 9 - - HYPH cord-014597-66vd2mdu 361 10 batches batch NNS cord-014597-66vd2mdu 361 11 that that WDT cord-014597-66vd2mdu 361 12 were be VBD cord-014597-66vd2mdu 361 13 conducted conduct VBN cord-014597-66vd2mdu 361 14 with with IN cord-014597-66vd2mdu 361 15 the the DT cord-014597-66vd2mdu 361 16 newly newly RB cord-014597-66vd2mdu 361 17 selected select VBN cord-014597-66vd2mdu 361 18 basal basal NN cord-014597-66vd2mdu 361 19 and and CC cord-014597-66vd2mdu 361 20 feed feed NN cord-014597-66vd2mdu 361 21 media medium NNS cord-014597-66vd2mdu 361 22 altered alter VBD cord-014597-66vd2mdu 361 23 the the DT cord-014597-66vd2mdu 361 24 distribution distribution NN cord-014597-66vd2mdu 361 25 of of IN cord-014597-66vd2mdu 361 26 charge charge NN cord-014597-66vd2mdu 361 27 and and CC cord-014597-66vd2mdu 361 28 glycan glycan NN cord-014597-66vd2mdu 361 29 variants variant NNS cord-014597-66vd2mdu 361 30 . . . cord-014597-66vd2mdu 362 1 The the DT cord-014597-66vd2mdu 362 2 amount amount NN cord-014597-66vd2mdu 362 3 of of IN cord-014597-66vd2mdu 362 4 aggregated aggregated JJ cord-014597-66vd2mdu 362 5 product product NN cord-014597-66vd2mdu 362 6 was be VBD cord-014597-66vd2mdu 362 7 not not RB cord-014597-66vd2mdu 362 8 altered alter VBN cord-014597-66vd2mdu 362 9 . . . cord-014597-66vd2mdu 363 1 The the DT cord-014597-66vd2mdu 363 2 established established JJ cord-014597-66vd2mdu 363 3 methodology methodology NN cord-014597-66vd2mdu 363 4 for for IN cord-014597-66vd2mdu 363 5 fed fed JJ cord-014597-66vd2mdu 363 6 - - HYPH cord-014597-66vd2mdu 363 7 batch batch NN cord-014597-66vd2mdu 363 8 development development NN cord-014597-66vd2mdu 363 9 is be VBZ cord-014597-66vd2mdu 363 10 a a DT cord-014597-66vd2mdu 363 11 rapid rapid JJ cord-014597-66vd2mdu 363 12 protocol protocol NN cord-014597-66vd2mdu 363 13 to to TO cord-014597-66vd2mdu 363 14 select select VB cord-014597-66vd2mdu 363 15 well well RB cord-014597-66vd2mdu 363 16 - - HYPH cord-014597-66vd2mdu 363 17 performing perform VBG cord-014597-66vd2mdu 363 18 feed feed NN cord-014597-66vd2mdu 363 19 supplements supplement NNS cord-014597-66vd2mdu 363 20 and and CC cord-014597-66vd2mdu 363 21 optimize optimize VB cord-014597-66vd2mdu 363 22 their -PRON- PRP$ cord-014597-66vd2mdu 363 23 ratio ratio NN cord-014597-66vd2mdu 363 24 to to IN cord-014597-66vd2mdu 363 25 the the DT cord-014597-66vd2mdu 363 26 culture culture NN cord-014597-66vd2mdu 363 27 requirements requirement NNS cord-014597-66vd2mdu 363 28 . . . cord-014597-66vd2mdu 364 1 In in IN cord-014597-66vd2mdu 364 2 three three CD cord-014597-66vd2mdu 364 3 steps step NNS cord-014597-66vd2mdu 364 4 , , , cord-014597-66vd2mdu 364 5 mAb mAb NNS cord-014597-66vd2mdu 364 6 titers titer NNS cord-014597-66vd2mdu 364 7 were be VBD cord-014597-66vd2mdu 364 8 boosted boost VBN cord-014597-66vd2mdu 364 9 2.5x 2.5x CD cord-014597-66vd2mdu 364 10 from from IN cord-014597-66vd2mdu 364 11 1.9 1.9 CD cord-014597-66vd2mdu 364 12 g g NN cord-014597-66vd2mdu 364 13 / / SYM cord-014597-66vd2mdu 364 14 L l NN cord-014597-66vd2mdu 364 15 to to IN cord-014597-66vd2mdu 364 16 4.9 4.9 CD cord-014597-66vd2mdu 364 17 g g NN cord-014597-66vd2mdu 364 18 / / SYM cord-014597-66vd2mdu 364 19 L. L. NNP cord-014597-66vd2mdu 364 20 Product Product NNP cord-014597-66vd2mdu 364 21 glycosylation glycosylation NN cord-014597-66vd2mdu 364 22 and and CC cord-014597-66vd2mdu 364 23 charge charge NN cord-014597-66vd2mdu 364 24 variants variant NNS cord-014597-66vd2mdu 364 25 could could MD cord-014597-66vd2mdu 364 26 be be VB cord-014597-66vd2mdu 364 27 influenced influence VBN cord-014597-66vd2mdu 364 28 by by IN cord-014597-66vd2mdu 364 29 the the DT cord-014597-66vd2mdu 364 30 newly newly RB cord-014597-66vd2mdu 364 31 selected select VBN cord-014597-66vd2mdu 364 32 basal basal NN cord-014597-66vd2mdu 364 33 and and CC cord-014597-66vd2mdu 364 34 feed feed NN cord-014597-66vd2mdu 364 35 media medium NNS cord-014597-66vd2mdu 364 36 compared compare VBN cord-014597-66vd2mdu 364 37 to to IN cord-014597-66vd2mdu 364 38 a a DT cord-014597-66vd2mdu 364 39 legacy legacy NN cord-014597-66vd2mdu 364 40 fed feed VBN cord-014597-66vd2mdu 364 41 - - HYPH cord-014597-66vd2mdu 364 42 batch batch NN cord-014597-66vd2mdu 364 43 process process NN cord-014597-66vd2mdu 364 44 . . . cord-014597-66vd2mdu 365 1 The the DT cord-014597-66vd2mdu 365 2 amount amount NN cord-014597-66vd2mdu 365 3 of of IN cord-014597-66vd2mdu 365 4 aggregated aggregated JJ cord-014597-66vd2mdu 365 5 product product NN cord-014597-66vd2mdu 365 6 was be VBD cord-014597-66vd2mdu 365 7 not not RB cord-014597-66vd2mdu 365 8 altered alter VBN cord-014597-66vd2mdu 365 9 . . . cord-014597-66vd2mdu 366 1 The the DT cord-014597-66vd2mdu 366 2 present present JJ cord-014597-66vd2mdu 366 3 study study NN cord-014597-66vd2mdu 366 4 investigates investigate VBZ cord-014597-66vd2mdu 366 5 the the DT cord-014597-66vd2mdu 366 6 beneficial beneficial JJ cord-014597-66vd2mdu 366 7 effect effect NN cord-014597-66vd2mdu 366 8 of of IN cord-014597-66vd2mdu 366 9 spiking spike VBG cord-014597-66vd2mdu 366 10 HyClone HyClone NNP cord-014597-66vd2mdu 366 11 ™ ™ NN cord-014597-66vd2mdu 366 12 ActiPro ActiPro NNP cord-014597-66vd2mdu 366 13 ™ ™ NN cord-014597-66vd2mdu 366 14 basal basal NN cord-014597-66vd2mdu 366 15 medium medium NN cord-014597-66vd2mdu 366 16 with with IN cord-014597-66vd2mdu 366 17 HyClone HyClone NNP cord-014597-66vd2mdu 366 18 Cell Cell NNP cord-014597-66vd2mdu 366 19 Boost Boost NNP cord-014597-66vd2mdu 366 20 ™ ™ CD cord-014597-66vd2mdu 366 21 7a 7a NN cord-014597-66vd2mdu 366 22 and and CC cord-014597-66vd2mdu 366 23 Cell cell NN cord-014597-66vd2mdu 366 24 Boost boost NN cord-014597-66vd2mdu 366 25 7b 7b NN cord-014597-66vd2mdu 366 26 feed feed VBP cord-014597-66vd2mdu 366 27 supplements supplement NNS cord-014597-66vd2mdu 366 28 on on IN cord-014597-66vd2mdu 366 29 growth growth NN cord-014597-66vd2mdu 366 30 and and CC cord-014597-66vd2mdu 366 31 productivity productivity NN cord-014597-66vd2mdu 366 32 of of IN cord-014597-66vd2mdu 366 33 a a DT cord-014597-66vd2mdu 366 34 recombinant recombinant JJ cord-014597-66vd2mdu 366 35 CHO CHO NNP cord-014597-66vd2mdu 366 36 cell cell NN cord-014597-66vd2mdu 366 37 line line NN cord-014597-66vd2mdu 366 38 . . . cord-014597-66vd2mdu 367 1 To to TO cord-014597-66vd2mdu 367 2 evaluate evaluate VB cord-014597-66vd2mdu 367 3 the the DT cord-014597-66vd2mdu 367 4 impact impact NN cord-014597-66vd2mdu 367 5 of of IN cord-014597-66vd2mdu 367 6 feed feed NN cord-014597-66vd2mdu 367 7 - - HYPH cord-014597-66vd2mdu 367 8 spiking spiking NN cord-014597-66vd2mdu 367 9 compared compare VBN cord-014597-66vd2mdu 367 10 with with IN cord-014597-66vd2mdu 367 11 cultivation cultivation NN cord-014597-66vd2mdu 367 12 in in IN cord-014597-66vd2mdu 367 13 basal basal NN cord-014597-66vd2mdu 367 14 medium medium NN cord-014597-66vd2mdu 367 15 only only RB cord-014597-66vd2mdu 367 16 , , , cord-014597-66vd2mdu 367 17 the the DT cord-014597-66vd2mdu 367 18 cell cell NN cord-014597-66vd2mdu 367 19 line line NN cord-014597-66vd2mdu 367 20 was be VBD cord-014597-66vd2mdu 367 21 grown grow VBN cord-014597-66vd2mdu 367 22 in in IN cord-014597-66vd2mdu 367 23 bioreactors bioreactor NNS cord-014597-66vd2mdu 367 24 under under IN cord-014597-66vd2mdu 367 25 controlled control VBN cord-014597-66vd2mdu 367 26 conditions condition NNS cord-014597-66vd2mdu 367 27 to to TO cord-014597-66vd2mdu 367 28 determine determine VB cord-014597-66vd2mdu 367 29 cellspecific cellspecific JJ cord-014597-66vd2mdu 367 30 metabolic metabolic JJ cord-014597-66vd2mdu 367 31 rates rate NNS cord-014597-66vd2mdu 367 32 , , , cord-014597-66vd2mdu 367 33 nutrient nutrient NN cord-014597-66vd2mdu 367 34 consumption consumption NN cord-014597-66vd2mdu 367 35 , , , cord-014597-66vd2mdu 367 36 and and CC cord-014597-66vd2mdu 367 37 byproduct byproduct NN cord-014597-66vd2mdu 367 38 accumulation accumulation NN cord-014597-66vd2mdu 367 39 over over IN cord-014597-66vd2mdu 367 40 the the DT cord-014597-66vd2mdu 367 41 process process NN cord-014597-66vd2mdu 367 42 time time NN cord-014597-66vd2mdu 367 43 . . . cord-014597-66vd2mdu 368 1 Transcriptome Transcriptome NNP cord-014597-66vd2mdu 368 2 analysis analysis NN cord-014597-66vd2mdu 368 3 of of IN cord-014597-66vd2mdu 368 4 the the DT cord-014597-66vd2mdu 368 5 cultivated cultivate VBN cord-014597-66vd2mdu 368 6 cells cell NNS cord-014597-66vd2mdu 368 7 , , , cord-014597-66vd2mdu 368 8 using use VBG cord-014597-66vd2mdu 368 9 microarrays microarray NNS cord-014597-66vd2mdu 368 10 on on IN cord-014597-66vd2mdu 368 11 four four CD cord-014597-66vd2mdu 368 12 consecutive consecutive JJ cord-014597-66vd2mdu 368 13 days day NNS cord-014597-66vd2mdu 368 14 to to TO cord-014597-66vd2mdu 368 15 investigate investigate VB cord-014597-66vd2mdu 368 16 differential differential JJ cord-014597-66vd2mdu 368 17 gene gene NN cord-014597-66vd2mdu 368 18 expression expression NN cord-014597-66vd2mdu 368 19 , , , cord-014597-66vd2mdu 368 20 revealed reveal VBD cord-014597-66vd2mdu 368 21 the the DT cord-014597-66vd2mdu 368 22 beneficial beneficial JJ cord-014597-66vd2mdu 368 23 effect effect NN cord-014597-66vd2mdu 368 24 of of IN cord-014597-66vd2mdu 368 25 feed feed NN cord-014597-66vd2mdu 368 26 - - HYPH cord-014597-66vd2mdu 368 27 spiking spiking NN cord-014597-66vd2mdu 368 28 compared compare VBN cord-014597-66vd2mdu 368 29 with with IN cord-014597-66vd2mdu 368 30 cells cell NNS cord-014597-66vd2mdu 368 31 grown grow VBN cord-014597-66vd2mdu 368 32 in in IN cord-014597-66vd2mdu 368 33 basal basal NN cord-014597-66vd2mdu 368 34 medium medium NN cord-014597-66vd2mdu 368 35 . . . cord-014597-66vd2mdu 369 1 Model model NN cord-014597-66vd2mdu 369 2 cell cell NN cord-014597-66vd2mdu 369 3 line line NN cord-014597-66vd2mdu 369 4 was be VBD cord-014597-66vd2mdu 369 5 a a DT cord-014597-66vd2mdu 369 6 mAb mab NN cord-014597-66vd2mdu 369 7 - - HYPH cord-014597-66vd2mdu 369 8 expressing express VBG cord-014597-66vd2mdu 369 9 CHO CHO NNP cord-014597-66vd2mdu 369 10 DG44 DG44 NNP cord-014597-66vd2mdu 369 11 ( ( -LRB- cord-014597-66vd2mdu 369 12 licensed license VBN cord-014597-66vd2mdu 369 13 from from IN cord-014597-66vd2mdu 369 14 Cellca Cellca NNP cord-014597-66vd2mdu 369 15 GmbH GmbH NNP cord-014597-66vd2mdu 369 16 ) ) -RRB- cord-014597-66vd2mdu 369 17 cultivated cultivate VBD cord-014597-66vd2mdu 369 18 either either CC cord-014597-66vd2mdu 369 19 in in IN cord-014597-66vd2mdu 369 20 ActiPro ActiPro NNP cord-014597-66vd2mdu 369 21 basal basal NN cord-014597-66vd2mdu 369 22 medium medium NN cord-014597-66vd2mdu 369 23 only only RB cord-014597-66vd2mdu 369 24 ( ( -LRB- cord-014597-66vd2mdu 369 25 GE GE NNP cord-014597-66vd2mdu 369 26 Healthcare Healthcare NNP cord-014597-66vd2mdu 369 27 ) ) -RRB- cord-014597-66vd2mdu 369 28 or or CC cord-014597-66vd2mdu 369 29 in in IN cord-014597-66vd2mdu 369 30 ActiPro ActiPro NNP cord-014597-66vd2mdu 369 31 basal basal NN cord-014597-66vd2mdu 369 32 medium medium NN cord-014597-66vd2mdu 369 33 feed feed NN cord-014597-66vd2mdu 369 34 - - HYPH cord-014597-66vd2mdu 369 35 spiked spike VBN cord-014597-66vd2mdu 369 36 with with IN cord-014597-66vd2mdu 369 37 additional additional JJ cord-014597-66vd2mdu 369 38 supplementation supplementation NN cord-014597-66vd2mdu 369 39 with with IN cord-014597-66vd2mdu 369 40 7 7 CD cord-014597-66vd2mdu 369 41 % % NN cord-014597-66vd2mdu 369 42 Cell cell NN cord-014597-66vd2mdu 369 43 Boost Boost NNP cord-014597-66vd2mdu 369 44 7a 7a NN cord-014597-66vd2mdu 369 45 and and CC cord-014597-66vd2mdu 369 46 0.7 0.7 CD cord-014597-66vd2mdu 369 47 % % NN cord-014597-66vd2mdu 369 48 Cell cell NN cord-014597-66vd2mdu 369 49 Boost boost NN cord-014597-66vd2mdu 369 50 7b 7b NN cord-014597-66vd2mdu 369 51 ( ( -LRB- cord-014597-66vd2mdu 369 52 GE GE NNP cord-014597-66vd2mdu 369 53 Healthcare Healthcare NNP cord-014597-66vd2mdu 369 54 ) ) -RRB- cord-014597-66vd2mdu 369 55 . . . cord-014597-66vd2mdu 370 1 Both both DT cord-014597-66vd2mdu 370 2 cultures culture NNS cord-014597-66vd2mdu 370 3 were be VBD cord-014597-66vd2mdu 370 4 grown grow VBN cord-014597-66vd2mdu 370 5 in in IN cord-014597-66vd2mdu 370 6 batch batch NN cord-014597-66vd2mdu 370 7 mode mode NN cord-014597-66vd2mdu 370 8 using use VBG cord-014597-66vd2mdu 370 9 DASGIP DASGIP NNP cord-014597-66vd2mdu 370 10 ™ ™ HYPH cord-014597-66vd2mdu 370 11 CellFerm CellFerm NNP cord-014597-66vd2mdu 370 12 - - HYPH cord-014597-66vd2mdu 370 13 Pro Pro NNP cord-014597-66vd2mdu 370 14 ™ ™ NN cord-014597-66vd2mdu 370 15 stirred stir VBN cord-014597-66vd2mdu 370 16 - - HYPH cord-014597-66vd2mdu 370 17 tank tank NN cord-014597-66vd2mdu 370 18 bioreactors bioreactor NNS cord-014597-66vd2mdu 370 19 ( ( -LRB- cord-014597-66vd2mdu 370 20 Eppendorf Eppendorf NNP cord-014597-66vd2mdu 370 21 ) ) -RRB- cord-014597-66vd2mdu 370 22 . . . cord-014597-66vd2mdu 371 1 The the DT cord-014597-66vd2mdu 371 2 beneficial beneficial JJ cord-014597-66vd2mdu 371 3 effect effect NN cord-014597-66vd2mdu 371 4 of of IN cord-014597-66vd2mdu 371 5 feed feed NN cord-014597-66vd2mdu 371 6 - - HYPH cord-014597-66vd2mdu 371 7 spiking spiking NN cord-014597-66vd2mdu 371 8 was be VBD cord-014597-66vd2mdu 371 9 analysed analyse VBN cord-014597-66vd2mdu 371 10 by by IN cord-014597-66vd2mdu 371 11 transcriptome transcriptome NN cord-014597-66vd2mdu 371 12 analysis analysis NN cord-014597-66vd2mdu 371 13 using use VBG cord-014597-66vd2mdu 371 14 microarray microarray NN cord-014597-66vd2mdu 371 15 technology technology NN cord-014597-66vd2mdu 371 16 ( ( -LRB- cord-014597-66vd2mdu 371 17 8×60 8×60 CD cord-014597-66vd2mdu 371 18 k k NN cord-014597-66vd2mdu 371 19 design design NN cord-014597-66vd2mdu 371 20 , , , cord-014597-66vd2mdu 371 21 Agilent Agilent NNP cord-014597-66vd2mdu 371 22 ) ) -RRB- cord-014597-66vd2mdu 371 23 . . . cord-014597-66vd2mdu 372 1 Both both DT cord-014597-66vd2mdu 372 2 basal basal NN cord-014597-66vd2mdu 372 3 and and CC cord-014597-66vd2mdu 372 4 feed feed NN cord-014597-66vd2mdu 372 5 - - HYPH cord-014597-66vd2mdu 372 6 spiked spike VBN cord-014597-66vd2mdu 372 7 processes process NNS cord-014597-66vd2mdu 372 8 lasted last VBD cord-014597-66vd2mdu 372 9 for for IN cord-014597-66vd2mdu 372 10 seven seven CD cord-014597-66vd2mdu 372 11 days day NNS cord-014597-66vd2mdu 372 12 with with IN cord-014597-66vd2mdu 372 13 viabilities viability NNS cord-014597-66vd2mdu 372 14 above above IN cord-014597-66vd2mdu 372 15 95 95 CD cord-014597-66vd2mdu 372 16 % % NN cord-014597-66vd2mdu 372 17 until until IN cord-014597-66vd2mdu 372 18 Day day NN cord-014597-66vd2mdu 372 19 6 6 CD cord-014597-66vd2mdu 372 20 . . . cord-014597-66vd2mdu 373 1 On on IN cord-014597-66vd2mdu 373 2 day day NN cord-014597-66vd2mdu 373 3 seven seven CD cord-014597-66vd2mdu 373 4 , , , cord-014597-66vd2mdu 373 5 a a DT cord-014597-66vd2mdu 373 6 sharp sharp JJ cord-014597-66vd2mdu 373 7 decline decline NN cord-014597-66vd2mdu 373 8 in in IN cord-014597-66vd2mdu 373 9 viability viability NN cord-014597-66vd2mdu 373 10 indicated indicate VBD cord-014597-66vd2mdu 373 11 the the DT cord-014597-66vd2mdu 373 12 end end NN cord-014597-66vd2mdu 373 13 of of IN cord-014597-66vd2mdu 373 14 the the DT cord-014597-66vd2mdu 373 15 batch batch NN cord-014597-66vd2mdu 373 16 process process NN cord-014597-66vd2mdu 373 17 ( ( -LRB- cord-014597-66vd2mdu 373 18 Fig Fig NNP cord-014597-66vd2mdu 373 19 . . . cord-014597-66vd2mdu 373 20 1a 1a CD cord-014597-66vd2mdu 373 21 ) ) -RRB- cord-014597-66vd2mdu 373 22 . . . cord-014597-66vd2mdu 374 1 In in IN cord-014597-66vd2mdu 374 2 feed feed NN cord-014597-66vd2mdu 374 3 - - HYPH cord-014597-66vd2mdu 374 4 spiked spike VBN cord-014597-66vd2mdu 374 5 medium medium NN cord-014597-66vd2mdu 374 6 , , , cord-014597-66vd2mdu 374 7 cells cell NNS cord-014597-66vd2mdu 374 8 initially initially RB cord-014597-66vd2mdu 374 9 grew grow VBD cord-014597-66vd2mdu 374 10 slower slow RBR cord-014597-66vd2mdu 374 11 but but CC cord-014597-66vd2mdu 374 12 reached reach VBD cord-014597-66vd2mdu 374 13 almost almost RB cord-014597-66vd2mdu 374 14 twice twice PDT cord-014597-66vd2mdu 374 15 as as RB cord-014597-66vd2mdu 374 16 high high JJ cord-014597-66vd2mdu 374 17 peak peak NN cord-014597-66vd2mdu 374 18 cell cell NN cord-014597-66vd2mdu 374 19 concentrations concentration NNS cord-014597-66vd2mdu 374 20 ( ( -LRB- cord-014597-66vd2mdu 374 21 17.6 17.6 CD cord-014597-66vd2mdu 374 22 × × NN cord-014597-66vd2mdu 374 23 10 10 CD cord-014597-66vd2mdu 374 24 6 6 CD cord-014597-66vd2mdu 374 25 c c NN cord-014597-66vd2mdu 374 26 / / SYM cord-014597-66vd2mdu 374 27 mL ml NN cord-014597-66vd2mdu 374 28 ) ) -RRB- cord-014597-66vd2mdu 374 29 than than IN cord-014597-66vd2mdu 374 30 in in IN cord-014597-66vd2mdu 374 31 basal basal NN cord-014597-66vd2mdu 374 32 medium medium NN cord-014597-66vd2mdu 374 33 only only RB cord-014597-66vd2mdu 374 34 ( ( -LRB- cord-014597-66vd2mdu 374 35 9.79 9.79 CD cord-014597-66vd2mdu 374 36 × × NN cord-014597-66vd2mdu 374 37 10 10 CD cord-014597-66vd2mdu 374 38 6 6 CD cord-014597-66vd2mdu 374 39 c c NN cord-014597-66vd2mdu 374 40 / / SYM cord-014597-66vd2mdu 374 41 mL ml NN cord-014597-66vd2mdu 374 42 ) ) -RRB- cord-014597-66vd2mdu 374 43 . . . cord-014597-66vd2mdu 375 1 Remarkably remarkably RB cord-014597-66vd2mdu 375 2 , , , cord-014597-66vd2mdu 375 3 the the DT cord-014597-66vd2mdu 375 4 integral integral NN cord-014597-66vd2mdu 375 5 of of IN cord-014597-66vd2mdu 375 6 the the DT cord-014597-66vd2mdu 375 7 viable viable JJ cord-014597-66vd2mdu 375 8 cell cell NN cord-014597-66vd2mdu 375 9 concentration concentration NN cord-014597-66vd2mdu 375 10 over over IN cord-014597-66vd2mdu 375 11 the the DT cord-014597-66vd2mdu 375 12 total total JJ cord-014597-66vd2mdu 375 13 process process NN cord-014597-66vd2mdu 375 14 time time NN cord-014597-66vd2mdu 375 15 ( ( -LRB- cord-014597-66vd2mdu 375 16 viable viable JJ cord-014597-66vd2mdu 375 17 cumulative cumulative JJ cord-014597-66vd2mdu 375 18 cell cell NN cord-014597-66vd2mdu 375 19 days day NNS cord-014597-66vd2mdu 375 20 [ [ -LRB- cord-014597-66vd2mdu 375 21 VCCD VCCD NNP cord-014597-66vd2mdu 375 22 ] ] -RRB- cord-014597-66vd2mdu 375 23 ) ) -RRB- cord-014597-66vd2mdu 375 24 was be VBD cord-014597-66vd2mdu 375 25 similar similar JJ cord-014597-66vd2mdu 375 26 between between IN cord-014597-66vd2mdu 375 27 both both DT cord-014597-66vd2mdu 375 28 process process NN cord-014597-66vd2mdu 375 29 strategies strategy NNS cord-014597-66vd2mdu 375 30 ( ( -LRB- cord-014597-66vd2mdu 375 31 Fig Fig NNP cord-014597-66vd2mdu 375 32 . . . cord-014597-66vd2mdu 375 33 1c 1c CD cord-014597-66vd2mdu 375 34 ) ) -RRB- cord-014597-66vd2mdu 375 35 . . . cord-014597-66vd2mdu 376 1 While while IN cord-014597-66vd2mdu 376 2 mAb mab NN cord-014597-66vd2mdu 376 3 production production NN cord-014597-66vd2mdu 376 4 plateaued plateaue VBD cord-014597-66vd2mdu 376 5 after after IN cord-014597-66vd2mdu 376 6 Day day NN cord-014597-66vd2mdu 376 7 4 4 CD cord-014597-66vd2mdu 376 8 in in IN cord-014597-66vd2mdu 376 9 basal basal NN cord-014597-66vd2mdu 376 10 medium medium NN cord-014597-66vd2mdu 376 11 only only RB cord-014597-66vd2mdu 376 12 ( ( -LRB- cord-014597-66vd2mdu 376 13 final final JJ cord-014597-66vd2mdu 376 14 titer titer NN cord-014597-66vd2mdu 376 15 0.8 0.8 CD cord-014597-66vd2mdu 376 16 g g NN cord-014597-66vd2mdu 376 17 / / SYM cord-014597-66vd2mdu 376 18 L L NNP cord-014597-66vd2mdu 376 19 ) ) -RRB- cord-014597-66vd2mdu 376 20 , , , cord-014597-66vd2mdu 376 21 a a DT cord-014597-66vd2mdu 376 22 continuous continuous JJ cord-014597-66vd2mdu 376 23 increase increase NN cord-014597-66vd2mdu 376 24 to to IN cord-014597-66vd2mdu 376 25 three three CD cord-014597-66vd2mdu 376 26 - - HYPH cord-014597-66vd2mdu 376 27 fold fold VB cord-014597-66vd2mdu 376 28 higher high JJR cord-014597-66vd2mdu 376 29 final final JJ cord-014597-66vd2mdu 376 30 titers titer NNS cord-014597-66vd2mdu 376 31 ( ( -LRB- cord-014597-66vd2mdu 376 32 2.4 2.4 CD cord-014597-66vd2mdu 376 33 g g NN cord-014597-66vd2mdu 376 34 / / SYM cord-014597-66vd2mdu 376 35 L L NNP cord-014597-66vd2mdu 376 36 ) ) -RRB- cord-014597-66vd2mdu 376 37 was be VBD cord-014597-66vd2mdu 376 38 observed observe VBN cord-014597-66vd2mdu 376 39 in in IN cord-014597-66vd2mdu 376 40 feed feed NN cord-014597-66vd2mdu 376 41 - - HYPH cord-014597-66vd2mdu 376 42 spiked spike VBN cord-014597-66vd2mdu 376 43 medium medium NN cord-014597-66vd2mdu 376 44 ( ( -LRB- cord-014597-66vd2mdu 376 45 Fig Fig NNP cord-014597-66vd2mdu 376 46 . . . cord-014597-66vd2mdu 376 47 1b 1b CD cord-014597-66vd2mdu 376 48 ) ) -RRB- cord-014597-66vd2mdu 376 49 . . . cord-014597-66vd2mdu 377 1 The the DT cord-014597-66vd2mdu 377 2 higher high JJR cord-014597-66vd2mdu 377 3 titers titer NNS cord-014597-66vd2mdu 377 4 could could MD cord-014597-66vd2mdu 377 5 be be VB cord-014597-66vd2mdu 377 6 attributed attribute VBN cord-014597-66vd2mdu 377 7 to to IN cord-014597-66vd2mdu 377 8 generally generally RB cord-014597-66vd2mdu 377 9 higher high JJR cord-014597-66vd2mdu 377 10 cell cell NN cord-014597-66vd2mdu 377 11 - - HYPH cord-014597-66vd2mdu 377 12 specific specific JJ cord-014597-66vd2mdu 377 13 productivities productivity NNS cord-014597-66vd2mdu 377 14 ( ( -LRB- cord-014597-66vd2mdu 377 15 qP qP NNP cord-014597-66vd2mdu 377 16 ) ) -RRB- cord-014597-66vd2mdu 377 17 , , , cord-014597-66vd2mdu 377 18 which which WDT cord-014597-66vd2mdu 377 19 remained remain VBD cord-014597-66vd2mdu 377 20 rather rather RB cord-014597-66vd2mdu 377 21 constant constant JJ cord-014597-66vd2mdu 377 22 ( ( -LRB- cord-014597-66vd2mdu 377 23 ~70 ~70 NFP cord-014597-66vd2mdu 377 24 pg pg NN cord-014597-66vd2mdu 377 25 / / SYM cord-014597-66vd2mdu 377 26 cell cell NN cord-014597-66vd2mdu 377 27 / / SYM cord-014597-66vd2mdu 377 28 day day NN cord-014597-66vd2mdu 377 29 ) ) -RRB- cord-014597-66vd2mdu 377 30 in in IN cord-014597-66vd2mdu 377 31 feedspiked feedspiked JJ cord-014597-66vd2mdu 377 32 cultures culture NNS cord-014597-66vd2mdu 377 33 . . . cord-014597-66vd2mdu 378 1 In in IN cord-014597-66vd2mdu 378 2 basal basal NN cord-014597-66vd2mdu 378 3 medium medium NN cord-014597-66vd2mdu 378 4 , , , cord-014597-66vd2mdu 378 5 the the DT cord-014597-66vd2mdu 378 6 qP qP NNP cord-014597-66vd2mdu 378 7 continuously continuously RB cord-014597-66vd2mdu 378 8 dropped drop VBD cord-014597-66vd2mdu 378 9 by by IN cord-014597-66vd2mdu 378 10 20 20 CD cord-014597-66vd2mdu 378 11 % % NN cord-014597-66vd2mdu 378 12 ( ( -LRB- cord-014597-66vd2mdu 378 13 Day day NN cord-014597-66vd2mdu 378 14 0 0 CD cord-014597-66vd2mdu 378 15 to to IN cord-014597-66vd2mdu 378 16 3 3 CD cord-014597-66vd2mdu 378 17 ) ) -RRB- cord-014597-66vd2mdu 378 18 , , , cord-014597-66vd2mdu 378 19 50 50 CD cord-014597-66vd2mdu 378 20 % % NN cord-014597-66vd2mdu 378 21 ( ( -LRB- cord-014597-66vd2mdu 378 22 Day Day NNP cord-014597-66vd2mdu 378 23 4 4 CD cord-014597-66vd2mdu 378 24 ) ) -RRB- cord-014597-66vd2mdu 378 25 , , , cord-014597-66vd2mdu 378 26 and and CC cord-014597-66vd2mdu 378 27 > > XX cord-014597-66vd2mdu 378 28 90 90 CD cord-014597-66vd2mdu 378 29 % % NN cord-014597-66vd2mdu 378 30 ( ( -LRB- cord-014597-66vd2mdu 378 31 Day day NN cord-014597-66vd2mdu 378 32 5 5 CD cord-014597-66vd2mdu 378 33 to to IN cord-014597-66vd2mdu 378 34 7 7 CD cord-014597-66vd2mdu 378 35 ) ) -RRB- cord-014597-66vd2mdu 378 36 from from IN cord-014597-66vd2mdu 378 37 70 70 CD cord-014597-66vd2mdu 378 38 to to TO cord-014597-66vd2mdu 378 39 10 10 CD cord-014597-66vd2mdu 378 40 pg pg NN cord-014597-66vd2mdu 378 41 / / SYM cord-014597-66vd2mdu 378 42 cell cell NN cord-014597-66vd2mdu 378 43 / / SYM cord-014597-66vd2mdu 378 44 day day NN cord-014597-66vd2mdu 378 45 in in IN cord-014597-66vd2mdu 378 46 basal basal NN cord-014597-66vd2mdu 378 47 medium medium NN cord-014597-66vd2mdu 378 48 cultures culture NNS cord-014597-66vd2mdu 378 49 . . . cord-014597-66vd2mdu 379 1 In in IN cord-014597-66vd2mdu 379 2 average average JJ cord-014597-66vd2mdu 379 3 , , , cord-014597-66vd2mdu 379 4 the the DT cord-014597-66vd2mdu 379 5 qP qP NNP cord-014597-66vd2mdu 379 6 was be VBD cord-014597-66vd2mdu 379 7 70 70 CD cord-014597-66vd2mdu 379 8 % % NN cord-014597-66vd2mdu 379 9 higher high JJR cord-014597-66vd2mdu 379 10 in in IN cord-014597-66vd2mdu 379 11 feed feed NN cord-014597-66vd2mdu 379 12 - - HYPH cord-014597-66vd2mdu 379 13 spiked spike VBN cord-014597-66vd2mdu 379 14 cultures culture NNS cord-014597-66vd2mdu 379 15 ( ( -LRB- cord-014597-66vd2mdu 379 16 Fig Fig NNP cord-014597-66vd2mdu 379 17 . . . cord-014597-66vd2mdu 379 18 1d 1d CD cord-014597-66vd2mdu 379 19 ) ) -RRB- cord-014597-66vd2mdu 379 20 . . . cord-014597-66vd2mdu 380 1 Transcriptome Transcriptome NNP cord-014597-66vd2mdu 380 2 analysis analysis NN cord-014597-66vd2mdu 380 3 of of IN cord-014597-66vd2mdu 380 4 differentially differentially RB cord-014597-66vd2mdu 380 5 expressed express VBN cord-014597-66vd2mdu 380 6 genes gene NNS cord-014597-66vd2mdu 380 7 between between IN cord-014597-66vd2mdu 380 8 cells cell NNS cord-014597-66vd2mdu 380 9 grown grow VBN cord-014597-66vd2mdu 380 10 in in IN cord-014597-66vd2mdu 380 11 basal basal NN cord-014597-66vd2mdu 380 12 medium medium NN cord-014597-66vd2mdu 380 13 or or CC cord-014597-66vd2mdu 380 14 feed feed NN cord-014597-66vd2mdu 380 15 - - HYPH cord-014597-66vd2mdu 380 16 spiked spike VBN cord-014597-66vd2mdu 380 17 medium medium NN cord-014597-66vd2mdu 380 18 were be VBD cord-014597-66vd2mdu 380 19 used use VBN cord-014597-66vd2mdu 380 20 to to TO cord-014597-66vd2mdu 380 21 identify identify VB cord-014597-66vd2mdu 380 22 relevant relevant JJ cord-014597-66vd2mdu 380 23 GO GO NNP cord-014597-66vd2mdu 380 24 terms term NNS cord-014597-66vd2mdu 380 25 that that WDT cord-014597-66vd2mdu 380 26 indicated indicate VBD cord-014597-66vd2mdu 380 27 a a DT cord-014597-66vd2mdu 380 28 more more RBR cord-014597-66vd2mdu 380 29 active active JJ cord-014597-66vd2mdu 380 30 proliferative proliferative JJ cord-014597-66vd2mdu 380 31 state state NN cord-014597-66vd2mdu 380 32 for for IN cord-014597-66vd2mdu 380 33 feed feed NN cord-014597-66vd2mdu 380 34 - - HYPH cord-014597-66vd2mdu 380 35 spiked spike VBN cord-014597-66vd2mdu 380 36 cultures culture NNS cord-014597-66vd2mdu 380 37 ( ( -LRB- cord-014597-66vd2mdu 380 38 data datum NNS cord-014597-66vd2mdu 380 39 not not RB cord-014597-66vd2mdu 380 40 shown show VBN cord-014597-66vd2mdu 380 41 ) ) -RRB- cord-014597-66vd2mdu 380 42 . . . cord-014597-66vd2mdu 381 1 The the DT cord-014597-66vd2mdu 381 2 top top JJ cord-014597-66vd2mdu 381 3 GO GO NNP cord-014597-66vd2mdu 381 4 terms term NNS cord-014597-66vd2mdu 381 5 significantly significantly RB cord-014597-66vd2mdu 381 6 related relate VBN cord-014597-66vd2mdu 381 7 to to IN cord-014597-66vd2mdu 381 8 cell cell NN cord-014597-66vd2mdu 381 9 cycle cycle NN cord-014597-66vd2mdu 381 10 and and CC cord-014597-66vd2mdu 381 11 primary primary JJ cord-014597-66vd2mdu 381 12 metabolism metabolism NN cord-014597-66vd2mdu 381 13 , , , cord-014597-66vd2mdu 381 14 cellular cellular JJ cord-014597-66vd2mdu 381 15 division division NN cord-014597-66vd2mdu 381 16 , , , cord-014597-66vd2mdu 381 17 as as RB cord-014597-66vd2mdu 381 18 well well RB cord-014597-66vd2mdu 381 19 as as IN cord-014597-66vd2mdu 381 20 nucleobase nucleobase NNP cord-014597-66vd2mdu 381 21 formation formation NN cord-014597-66vd2mdu 381 22 or or CC cord-014597-66vd2mdu 381 23 regulation regulation NN cord-014597-66vd2mdu 381 24 . . . cord-014597-66vd2mdu 382 1 Furthermore furthermore RB cord-014597-66vd2mdu 382 2 , , , cord-014597-66vd2mdu 382 3 GSEA GSEA NNP cord-014597-66vd2mdu 382 4 revealed reveal VBD cord-014597-66vd2mdu 382 5 several several JJ cord-014597-66vd2mdu 382 6 significantly significantly RB cord-014597-66vd2mdu 382 7 enriched enrich VBN cord-014597-66vd2mdu 382 8 set set NN cord-014597-66vd2mdu 382 9 of of IN cord-014597-66vd2mdu 382 10 genes gene NNS cord-014597-66vd2mdu 382 11 related relate VBN cord-014597-66vd2mdu 382 12 to to IN cord-014597-66vd2mdu 382 13 gene gene NN cord-014597-66vd2mdu 382 14 transcription transcription NN cord-014597-66vd2mdu 382 15 , , , cord-014597-66vd2mdu 382 16 DNA dna NN cord-014597-66vd2mdu 382 17 replication replication NN cord-014597-66vd2mdu 382 18 and and CC cord-014597-66vd2mdu 382 19 repair repair NN cord-014597-66vd2mdu 382 20 , , , cord-014597-66vd2mdu 382 21 cell cell NN cord-014597-66vd2mdu 382 22 growth growth NN cord-014597-66vd2mdu 382 23 and and CC cord-014597-66vd2mdu 382 24 proliferation proliferation NN cord-014597-66vd2mdu 382 25 , , , cord-014597-66vd2mdu 382 26 as as RB cord-014597-66vd2mdu 382 27 well well RB cord-014597-66vd2mdu 382 28 as as IN cord-014597-66vd2mdu 382 29 inhibition inhibition NN cord-014597-66vd2mdu 382 30 of of IN cord-014597-66vd2mdu 382 31 apoptosis apoptosis NN cord-014597-66vd2mdu 382 32 in in IN cord-014597-66vd2mdu 382 33 feed feed NN cord-014597-66vd2mdu 382 34 - - HYPH cord-014597-66vd2mdu 382 35 spiked spike VBN cord-014597-66vd2mdu 382 36 cultures culture NNS cord-014597-66vd2mdu 382 37 . . . cord-014597-66vd2mdu 383 1 Thus thus RB cord-014597-66vd2mdu 383 2 , , , cord-014597-66vd2mdu 383 3 feed feed NN cord-014597-66vd2mdu 383 4 - - HYPH cord-014597-66vd2mdu 383 5 spiking spiking NN cord-014597-66vd2mdu 383 6 increased increase VBD cord-014597-66vd2mdu 383 7 the the DT cord-014597-66vd2mdu 383 8 proliferative proliferative JJ cord-014597-66vd2mdu 383 9 activity activity NN cord-014597-66vd2mdu 383 10 of of IN cord-014597-66vd2mdu 383 11 cultivated cultivate VBN cord-014597-66vd2mdu 383 12 cells cell NNS cord-014597-66vd2mdu 383 13 . . . cord-014597-66vd2mdu 384 1 Several several JJ cord-014597-66vd2mdu 384 2 of of IN cord-014597-66vd2mdu 384 3 the the DT cord-014597-66vd2mdu 384 4 identified identify VBN cord-014597-66vd2mdu 384 5 genes gene NNS cord-014597-66vd2mdu 384 6 appear appear VBP cord-014597-66vd2mdu 384 7 as as IN cord-014597-66vd2mdu 384 8 promising promising JJ cord-014597-66vd2mdu 384 9 targets target NNS cord-014597-66vd2mdu 384 10 for for IN cord-014597-66vd2mdu 384 11 cell cell NN cord-014597-66vd2mdu 384 12 line line NN cord-014597-66vd2mdu 384 13 engineering engineering NN cord-014597-66vd2mdu 384 14 , , , cord-014597-66vd2mdu 384 15 but but CC cord-014597-66vd2mdu 384 16 have have VBP cord-014597-66vd2mdu 384 17 not not RB cord-014597-66vd2mdu 384 18 yet yet RB cord-014597-66vd2mdu 384 19 been be VBN cord-014597-66vd2mdu 384 20 described describe VBN cord-014597-66vd2mdu 384 21 in in IN cord-014597-66vd2mdu 384 22 relation relation NN cord-014597-66vd2mdu 384 23 to to IN cord-014597-66vd2mdu 384 24 high high RB cord-014597-66vd2mdu 384 25 - - HYPH cord-014597-66vd2mdu 384 26 producing produce VBG cord-014597-66vd2mdu 384 27 recombinant recombinant JJ cord-014597-66vd2mdu 384 28 cell cell NN cord-014597-66vd2mdu 384 29 lines line NNS cord-014597-66vd2mdu 384 30 and and CC cord-014597-66vd2mdu 384 31 will will MD cord-014597-66vd2mdu 384 32 need need VB cord-014597-66vd2mdu 384 33 to to TO cord-014597-66vd2mdu 384 34 be be VB cord-014597-66vd2mdu 384 35 evaluated evaluate VBN cord-014597-66vd2mdu 384 36 in in IN cord-014597-66vd2mdu 384 37 future future JJ cord-014597-66vd2mdu 384 38 studies study NNS cord-014597-66vd2mdu 384 39 . . . cord-014597-66vd2mdu 385 1 Feed feed NN cord-014597-66vd2mdu 385 2 - - HYPH cord-014597-66vd2mdu 385 3 spiking spiking NN cord-014597-66vd2mdu 385 4 of of IN cord-014597-66vd2mdu 385 5 basal basal NN cord-014597-66vd2mdu 385 6 medium medium NN cord-014597-66vd2mdu 385 7 is be VBZ cord-014597-66vd2mdu 385 8 a a DT cord-014597-66vd2mdu 385 9 convenient convenient JJ cord-014597-66vd2mdu 385 10 and and CC cord-014597-66vd2mdu 385 11 easy easy JJ cord-014597-66vd2mdu 385 12 way way NN cord-014597-66vd2mdu 385 13 to to TO cord-014597-66vd2mdu 385 14 considerably considerably RB cord-014597-66vd2mdu 385 15 increase increase VB cord-014597-66vd2mdu 385 16 product product NN cord-014597-66vd2mdu 385 17 concentrations concentration NNS cord-014597-66vd2mdu 385 18 in in IN cord-014597-66vd2mdu 385 19 a a DT cord-014597-66vd2mdu 385 20 simple simple JJ cord-014597-66vd2mdu 385 21 batch batch NN cord-014597-66vd2mdu 385 22 culture culture NN cord-014597-66vd2mdu 385 23 . . . cord-014597-66vd2mdu 386 1 Differential differential JJ cord-014597-66vd2mdu 386 2 gene gene NN cord-014597-66vd2mdu 386 3 expression expression NN cord-014597-66vd2mdu 386 4 revealed reveal VBD cord-014597-66vd2mdu 386 5 genes gene NNS cord-014597-66vd2mdu 386 6 that that WDT cord-014597-66vd2mdu 386 7 appear appear VBP cord-014597-66vd2mdu 386 8 important important JJ cord-014597-66vd2mdu 386 9 for for IN cord-014597-66vd2mdu 386 10 high high JJ cord-014597-66vd2mdu 386 11 cell cell NN cord-014597-66vd2mdu 386 12 - - HYPH cord-014597-66vd2mdu 386 13 specific specific JJ cord-014597-66vd2mdu 386 14 production production NN cord-014597-66vd2mdu 386 15 rates rate NNS cord-014597-66vd2mdu 386 16 , , , cord-014597-66vd2mdu 386 17 and and CC cord-014597-66vd2mdu 386 18 this this DT cord-014597-66vd2mdu 386 19 knowledge knowledge NN cord-014597-66vd2mdu 386 20 can can MD cord-014597-66vd2mdu 386 21 be be VB cord-014597-66vd2mdu 386 22 leveraged leverage VBN cord-014597-66vd2mdu 386 23 into into IN cord-014597-66vd2mdu 386 24 cell cell NN cord-014597-66vd2mdu 386 25 line line NN cord-014597-66vd2mdu 386 26 engineering engineering NN cord-014597-66vd2mdu 386 27 approaches approach NNS cord-014597-66vd2mdu 386 28 or or CC cord-014597-66vd2mdu 386 29 the the DT cord-014597-66vd2mdu 386 30 design design NN cord-014597-66vd2mdu 386 31 of of IN cord-014597-66vd2mdu 386 32 high high JJ cord-014597-66vd2mdu 386 33 producing produce VBG cord-014597-66vd2mdu 386 34 CHO CHO NNP cord-014597-66vd2mdu 386 35 cell cell NN cord-014597-66vd2mdu 386 36 media medium NNS cord-014597-66vd2mdu 386 37 . . . cord-014597-66vd2mdu 387 1 In in IN cord-014597-66vd2mdu 387 2 the the DT cord-014597-66vd2mdu 387 3 latter latter JJ cord-014597-66vd2mdu 387 4 case case NN cord-014597-66vd2mdu 387 5 , , , cord-014597-66vd2mdu 387 6 a a DT cord-014597-66vd2mdu 387 7 maximized maximize VBN cord-014597-66vd2mdu 387 8 supply supply NN cord-014597-66vd2mdu 387 9 of of IN cord-014597-66vd2mdu 387 10 _SP cord-014597-66vd2mdu 387 11 High high JJ cord-014597-66vd2mdu 387 12 biosimilarity biosimilarity NN cord-014597-66vd2mdu 387 13 must must MD cord-014597-66vd2mdu 387 14 be be VB cord-014597-66vd2mdu 387 15 demonstrated demonstrate VBN cord-014597-66vd2mdu 387 16 by by IN cord-014597-66vd2mdu 387 17 physicochemical physicochemical JJ cord-014597-66vd2mdu 387 18 and and CC cord-014597-66vd2mdu 387 19 functional functional JJ cord-014597-66vd2mdu 387 20 characterization characterization NN cord-014597-66vd2mdu 387 21 for for IN cord-014597-66vd2mdu 387 22 approval approval NN cord-014597-66vd2mdu 387 23 requirements requirement NNS cord-014597-66vd2mdu 387 24 of of IN cord-014597-66vd2mdu 387 25 phase phase NN cord-014597-66vd2mdu 388 1 I -PRON- PRP cord-014597-66vd2mdu 388 2 and and CC cord-014597-66vd2mdu 388 3 phase phase NN cord-014597-66vd2mdu 388 4 III iii CD cord-014597-66vd2mdu 388 5 studies study NNS cord-014597-66vd2mdu 388 6 in in IN cord-014597-66vd2mdu 388 7 terms term NNS cord-014597-66vd2mdu 388 8 of of IN cord-014597-66vd2mdu 388 9 efficacy efficacy NN cord-014597-66vd2mdu 388 10 , , , cord-014597-66vd2mdu 388 11 safety safety NN cord-014597-66vd2mdu 388 12 and and CC cord-014597-66vd2mdu 388 13 immunogenicity immunogenicity NN cord-014597-66vd2mdu 388 14 . . . cord-014597-66vd2mdu 389 1 In in IN cord-014597-66vd2mdu 389 2 this this DT cord-014597-66vd2mdu 389 3 study study NN cord-014597-66vd2mdu 389 4 , , , cord-014597-66vd2mdu 389 5 rounds round NNS cord-014597-66vd2mdu 389 6 of of IN cord-014597-66vd2mdu 389 7 upstream upstream NN cord-014597-66vd2mdu 389 8 and and CC cord-014597-66vd2mdu 389 9 downstream downstream JJ cord-014597-66vd2mdu 389 10 processes process NNS cord-014597-66vd2mdu 389 11 were be VBD cord-014597-66vd2mdu 389 12 run run VBN cord-014597-66vd2mdu 389 13 to to TO cord-014597-66vd2mdu 389 14 reach reach VB cord-014597-66vd2mdu 389 15 the the DT cord-014597-66vd2mdu 389 16 CQA CQA NNP cord-014597-66vd2mdu 389 17 limits limit NNS cord-014597-66vd2mdu 389 18 of of IN cord-014597-66vd2mdu 389 19 the the DT cord-014597-66vd2mdu 389 20 originator originator NN cord-014597-66vd2mdu 389 21 molecule molecule NN cord-014597-66vd2mdu 389 22 . . . cord-014597-66vd2mdu 390 1 After after IN cord-014597-66vd2mdu 390 2 conducting conduct VBG cord-014597-66vd2mdu 390 3 many many JJ cord-014597-66vd2mdu 390 4 different different JJ cord-014597-66vd2mdu 390 5 development development NN cord-014597-66vd2mdu 390 6 strategies strategy NNS cord-014597-66vd2mdu 390 7 , , , cord-014597-66vd2mdu 390 8 the the DT cord-014597-66vd2mdu 390 9 mirror mirror NN cord-014597-66vd2mdu 390 10 plot plot NN cord-014597-66vd2mdu 390 11 images image NNS cord-014597-66vd2mdu 390 12 of of IN cord-014597-66vd2mdu 390 13 the the DT cord-014597-66vd2mdu 390 14 intact intact JJ cord-014597-66vd2mdu 390 15 deconvoluted deconvoluted JJ cord-014597-66vd2mdu 390 16 mass mass NN cord-014597-66vd2mdu 390 17 were be VBD cord-014597-66vd2mdu 390 18 found find VBN cord-014597-66vd2mdu 390 19 to to TO cord-014597-66vd2mdu 390 20 be be VB cord-014597-66vd2mdu 390 21 identical identical JJ cord-014597-66vd2mdu 390 22 corresponding correspond VBG cord-014597-66vd2mdu 390 23 to to IN cord-014597-66vd2mdu 390 24 similar similar JJ cord-014597-66vd2mdu 390 25 levels level NNS cord-014597-66vd2mdu 390 26 of of IN cord-014597-66vd2mdu 390 27 glycoforms glycoform NNS cord-014597-66vd2mdu 390 28 . . . cord-014597-66vd2mdu 391 1 The the DT cord-014597-66vd2mdu 391 2 UV uv NN cord-014597-66vd2mdu 391 3 chromatogram chromatogram NN cord-014597-66vd2mdu 391 4 of of IN cord-014597-66vd2mdu 391 5 reversed reversed JJ cord-014597-66vd2mdu 391 6 phase phase NN cord-014597-66vd2mdu 391 7 ultraperformance ultraperformance NN cord-014597-66vd2mdu 391 8 liquid liquid NN cord-014597-66vd2mdu 391 9 chromatography chromatography NN cord-014597-66vd2mdu 391 10 ( ( -LRB- cord-014597-66vd2mdu 391 11 RP RP NNP cord-014597-66vd2mdu 391 12 - - HYPH cord-014597-66vd2mdu 391 13 UPLC UPLC NNP cord-014597-66vd2mdu 391 14 ) ) -RRB- cord-014597-66vd2mdu 391 15 of of IN cord-014597-66vd2mdu 391 16 tryptic tryptic JJ cord-014597-66vd2mdu 391 17 peptide peptide NN cord-014597-66vd2mdu 391 18 mapping mapping NN cord-014597-66vd2mdu 391 19 demonstrated demonstrate VBD cord-014597-66vd2mdu 391 20 that that IN cord-014597-66vd2mdu 391 21 the the DT cord-014597-66vd2mdu 391 22 primary primary JJ cord-014597-66vd2mdu 391 23 structure structure NN cord-014597-66vd2mdu 391 24 of of IN cord-014597-66vd2mdu 391 25 TUR01 TUR01 NNP cord-014597-66vd2mdu 391 26 is be VBZ cord-014597-66vd2mdu 391 27 identical identical JJ cord-014597-66vd2mdu 391 28 to to IN cord-014597-66vd2mdu 391 29 the the DT cord-014597-66vd2mdu 391 30 originator originator NN cord-014597-66vd2mdu 391 31 as as IN cord-014597-66vd2mdu 391 32 shown show VBN cord-014597-66vd2mdu 391 33 in in IN cord-014597-66vd2mdu 391 34 Fig Fig NNP cord-014597-66vd2mdu 391 35 . . . cord-014597-66vd2mdu 392 1 1a 1a LS cord-014597-66vd2mdu 392 2 . . . cord-014597-66vd2mdu 393 1 Post post JJ cord-014597-66vd2mdu 393 2 - - JJ cord-014597-66vd2mdu 393 3 translational translational JJ cord-014597-66vd2mdu 393 4 modifications modification NNS cord-014597-66vd2mdu 393 5 ( ( -LRB- cord-014597-66vd2mdu 393 6 PTMs ptm NNS cord-014597-66vd2mdu 393 7 ) ) -RRB- cord-014597-66vd2mdu 393 8 such such JJ cord-014597-66vd2mdu 393 9 as as IN cord-014597-66vd2mdu 393 10 oxidation oxidation NN cord-014597-66vd2mdu 393 11 , , , cord-014597-66vd2mdu 393 12 deamidation deamidation NN cord-014597-66vd2mdu 393 13 , , , cord-014597-66vd2mdu 393 14 N n CD cord-014597-66vd2mdu 393 15 - - HYPH cord-014597-66vd2mdu 393 16 terminal terminal JJ cord-014597-66vd2mdu 393 17 pyroglutamic pyroglutamic JJ cord-014597-66vd2mdu 393 18 acid acid NN cord-014597-66vd2mdu 393 19 , , , cord-014597-66vd2mdu 393 20 C c NN cord-014597-66vd2mdu 393 21 - - HYPH cord-014597-66vd2mdu 393 22 terminal terminal NN cord-014597-66vd2mdu 393 23 lysine lysine NN cord-014597-66vd2mdu 393 24 truncation truncation NN cord-014597-66vd2mdu 393 25 levels level NNS cord-014597-66vd2mdu 393 26 were be VBD cord-014597-66vd2mdu 393 27 also also RB cord-014597-66vd2mdu 393 28 comparable comparable JJ cord-014597-66vd2mdu 393 29 for for IN cord-014597-66vd2mdu 393 30 two two CD cord-014597-66vd2mdu 393 31 products product NNS cord-014597-66vd2mdu 393 32 . . . cord-014597-66vd2mdu 394 1 The the DT cord-014597-66vd2mdu 394 2 glycosylation glycosylation NN cord-014597-66vd2mdu 394 3 site site NN cord-014597-66vd2mdu 394 4 ( ( -LRB- cord-014597-66vd2mdu 394 5 HC HC NNP cord-014597-66vd2mdu 394 6 - - HYPH cord-014597-66vd2mdu 394 7 Asn301 Asn301 NNP cord-014597-66vd2mdu 394 8 ) ) -RRB- cord-014597-66vd2mdu 394 9 was be VBD cord-014597-66vd2mdu 394 10 confirmed confirm VBN cord-014597-66vd2mdu 394 11 by by IN cord-014597-66vd2mdu 394 12 peptide peptide NN cord-014597-66vd2mdu 394 13 mapping mapping NN cord-014597-66vd2mdu 394 14 analysis analysis NN cord-014597-66vd2mdu 394 15 and and CC cord-014597-66vd2mdu 394 16 100 100 CD cord-014597-66vd2mdu 394 17 % % NN cord-014597-66vd2mdu 394 18 glycan glycan NN cord-014597-66vd2mdu 394 19 site site NN cord-014597-66vd2mdu 394 20 occupancy occupancy NN cord-014597-66vd2mdu 394 21 was be VBD cord-014597-66vd2mdu 394 22 proven prove VBN cord-014597-66vd2mdu 394 23 for for IN cord-014597-66vd2mdu 394 24 TUR01 TUR01 NNP cord-014597-66vd2mdu 394 25 and and CC cord-014597-66vd2mdu 394 26 originator originator NN cord-014597-66vd2mdu 394 27 . . . cord-014597-66vd2mdu 395 1 The the DT cord-014597-66vd2mdu 395 2 glycosylation glycosylation NN cord-014597-66vd2mdu 395 3 pattern pattern NN cord-014597-66vd2mdu 395 4 for for IN cord-014597-66vd2mdu 395 5 two two CD cord-014597-66vd2mdu 395 6 products product NNS cord-014597-66vd2mdu 395 7 were be VBD cord-014597-66vd2mdu 395 8 highly highly RB cord-014597-66vd2mdu 395 9 similar similar JJ cord-014597-66vd2mdu 395 10 in in IN cord-014597-66vd2mdu 395 11 terms term NNS cord-014597-66vd2mdu 395 12 of of IN cord-014597-66vd2mdu 395 13 major major JJ cord-014597-66vd2mdu 395 14 glycans glycan NNS cord-014597-66vd2mdu 395 15 ( ( -LRB- cord-014597-66vd2mdu 395 16 G0F G0F NNS cord-014597-66vd2mdu 395 17 , , , cord-014597-66vd2mdu 395 18 G1F g1f RB cord-014597-66vd2mdu 395 19 , , , cord-014597-66vd2mdu 395 20 G0F g0f NN cord-014597-66vd2mdu 395 21 - - HYPH cord-014597-66vd2mdu 395 22 GN gn NN cord-014597-66vd2mdu 395 23 and and CC cord-014597-66vd2mdu 395 24 etc etc NN cord-014597-66vd2mdu 395 25 . . . cord-014597-66vd2mdu 395 26 ) ) -RRB- cord-014597-66vd2mdu 395 27 . . . cord-014597-66vd2mdu 396 1 Man5 man5 JJ cord-014597-66vd2mdu 396 2 level level NN cord-014597-66vd2mdu 396 3 was be VBD cord-014597-66vd2mdu 396 4 lower low JJR cord-014597-66vd2mdu 396 5 in in IN cord-014597-66vd2mdu 396 6 TUR01 TUR01 NNS cord-014597-66vd2mdu 396 7 compared compare VBN cord-014597-66vd2mdu 396 8 to to IN cord-014597-66vd2mdu 396 9 the the DT cord-014597-66vd2mdu 396 10 originator originator NN cord-014597-66vd2mdu 396 11 product product NN cord-014597-66vd2mdu 396 12 which which WDT cord-014597-66vd2mdu 396 13 may may MD cord-014597-66vd2mdu 396 14 not not RB cord-014597-66vd2mdu 396 15 have have VB cord-014597-66vd2mdu 396 16 any any DT cord-014597-66vd2mdu 396 17 clinical clinical JJ cord-014597-66vd2mdu 396 18 effect effect NN cord-014597-66vd2mdu 396 19 on on IN cord-014597-66vd2mdu 396 20 the the DT cord-014597-66vd2mdu 396 21 molecule molecule NN cord-014597-66vd2mdu 396 22 . . . cord-014597-66vd2mdu 397 1 The the DT cord-014597-66vd2mdu 397 2 secondary secondary JJ cord-014597-66vd2mdu 397 3 structure structure NN cord-014597-66vd2mdu 397 4 was be VBD cord-014597-66vd2mdu 397 5 determined determine VBN cord-014597-66vd2mdu 397 6 by by IN cord-014597-66vd2mdu 397 7 ATR ATR NNP cord-014597-66vd2mdu 397 8 - - HYPH cord-014597-66vd2mdu 397 9 FTIR FTIR NNP cord-014597-66vd2mdu 397 10 spectroscopy spectroscopy NN cord-014597-66vd2mdu 397 11 . . . cord-014597-66vd2mdu 398 1 Absorption absorption NN cord-014597-66vd2mdu 398 2 bands band NNS cord-014597-66vd2mdu 398 3 ( ( -LRB- cord-014597-66vd2mdu 398 4 Amide Amide NNP cord-014597-66vd2mdu 398 5 I I NNP cord-014597-66vd2mdu 398 6 and and CC cord-014597-66vd2mdu 398 7 Amide Amide NNP cord-014597-66vd2mdu 398 8 II II NNP cord-014597-66vd2mdu 398 9 ) ) -RRB- cord-014597-66vd2mdu 398 10 were be VBD cord-014597-66vd2mdu 398 11 overlapped overlap VBN cord-014597-66vd2mdu 398 12 completely completely RB cord-014597-66vd2mdu 398 13 and and CC cord-014597-66vd2mdu 398 14 amounts amount NNS cord-014597-66vd2mdu 398 15 of of IN cord-014597-66vd2mdu 398 16 α α NN cord-014597-66vd2mdu 398 17 - - HYPH cord-014597-66vd2mdu 398 18 helix helix NN cord-014597-66vd2mdu 398 19 and and CC cord-014597-66vd2mdu 398 20 β β NN cord-014597-66vd2mdu 398 21 - - HYPH cord-014597-66vd2mdu 398 22 sheet sheet NN cord-014597-66vd2mdu 398 23 structures structure NNS cord-014597-66vd2mdu 398 24 were be VBD cord-014597-66vd2mdu 398 25 comparable comparable JJ cord-014597-66vd2mdu 398 26 . . . cord-014597-66vd2mdu 399 1 Furthermore furthermore RB cord-014597-66vd2mdu 399 2 ; ; : cord-014597-66vd2mdu 399 3 size size NN cord-014597-66vd2mdu 399 4 - - HYPH cord-014597-66vd2mdu 399 5 exclusion exclusion NN cord-014597-66vd2mdu 399 6 chromatography chromatography NN cord-014597-66vd2mdu 399 7 ( ( -LRB- cord-014597-66vd2mdu 399 8 SEC SEC NNP cord-014597-66vd2mdu 399 9 ) ) -RRB- cord-014597-66vd2mdu 399 10 analysis analysis NN cord-014597-66vd2mdu 399 11 revealed reveal VBD cord-014597-66vd2mdu 399 12 that that IN cord-014597-66vd2mdu 399 13 both both DT cord-014597-66vd2mdu 399 14 products product NNS cord-014597-66vd2mdu 399 15 have have VBP cord-014597-66vd2mdu 399 16 the the DT cord-014597-66vd2mdu 399 17 same same JJ cord-014597-66vd2mdu 399 18 level level NN cord-014597-66vd2mdu 399 19 of of IN cord-014597-66vd2mdu 399 20 purity purity NN cord-014597-66vd2mdu 399 21 ( ( -LRB- cord-014597-66vd2mdu 399 22 > > NFP cord-014597-66vd2mdu 399 23 99 99 CD cord-014597-66vd2mdu 399 24 % % NN cord-014597-66vd2mdu 399 25 ) ) -RRB- cord-014597-66vd2mdu 399 26 and and CC cord-014597-66vd2mdu 399 27 aggregate aggregate NN cord-014597-66vd2mdu 399 28 ( ( -LRB- cord-014597-66vd2mdu 399 29 < < NN cord-014597-66vd2mdu 399 30 1 1 CD cord-014597-66vd2mdu 399 31 % % NN cord-014597-66vd2mdu 399 32 ) ) -RRB- cord-014597-66vd2mdu 399 33 levels level NNS cord-014597-66vd2mdu 399 34 . . . cord-014597-66vd2mdu 400 1 The the DT cord-014597-66vd2mdu 400 2 level level NN cord-014597-66vd2mdu 400 3 of of IN cord-014597-66vd2mdu 400 4 impurities impurity NNS cord-014597-66vd2mdu 400 5 were be VBD cord-014597-66vd2mdu 400 6 determined determine VBN cord-014597-66vd2mdu 400 7 as as IN cord-014597-66vd2mdu 400 8 below below IN cord-014597-66vd2mdu 400 9 4 4 CD cord-014597-66vd2mdu 400 10 % % NN cord-014597-66vd2mdu 400 11 by by IN cord-014597-66vd2mdu 400 12 CE CE NNP cord-014597-66vd2mdu 400 13 - - HYPH cord-014597-66vd2mdu 400 14 SDS SDS NNP cord-014597-66vd2mdu 400 15 . . . cord-014597-66vd2mdu 401 1 The the DT cord-014597-66vd2mdu 401 2 capillary capillary NN cord-014597-66vd2mdu 401 3 isoelectric isoelectric JJ cord-014597-66vd2mdu 401 4 focusing focus VBG cord-014597-66vd2mdu 401 5 ( ( -LRB- cord-014597-66vd2mdu 402 1 cIEF cief LS cord-014597-66vd2mdu 402 2 ) ) -RRB- cord-014597-66vd2mdu 402 3 experiments experiment NNS cord-014597-66vd2mdu 402 4 showed show VBD cord-014597-66vd2mdu 402 5 that that IN cord-014597-66vd2mdu 402 6 the the DT cord-014597-66vd2mdu 402 7 charge charge NN cord-014597-66vd2mdu 402 8 variant variant NN cord-014597-66vd2mdu 402 9 profiles profile NNS cord-014597-66vd2mdu 402 10 of of IN cord-014597-66vd2mdu 402 11 two two CD cord-014597-66vd2mdu 402 12 products product NNS cord-014597-66vd2mdu 402 13 are be VBP cord-014597-66vd2mdu 402 14 indistinguishable indistinguishable JJ cord-014597-66vd2mdu 402 15 and and CC cord-014597-66vd2mdu 402 16 the the DT cord-014597-66vd2mdu 402 17 isoelectric isoelectric JJ cord-014597-66vd2mdu 402 18 point point NN cord-014597-66vd2mdu 402 19 of of IN cord-014597-66vd2mdu 402 20 main main JJ cord-014597-66vd2mdu 402 21 peak peak NN cord-014597-66vd2mdu 402 22 is be VBZ cord-014597-66vd2mdu 402 23 observed observe VBN cord-014597-66vd2mdu 402 24 at at IN cord-014597-66vd2mdu 402 25 8.3 8.3 CD cord-014597-66vd2mdu 402 26 for for IN cord-014597-66vd2mdu 402 27 both both DT cord-014597-66vd2mdu 402 28 products product NNS cord-014597-66vd2mdu 402 29 . . . cord-014597-66vd2mdu 403 1 The the DT cord-014597-66vd2mdu 403 2 association association NN cord-014597-66vd2mdu 403 3 / / SYM cord-014597-66vd2mdu 403 4 dissociation dissociation NN cord-014597-66vd2mdu 403 5 rate rate NN cord-014597-66vd2mdu 403 6 constants constant NNS cord-014597-66vd2mdu 403 7 and and CC cord-014597-66vd2mdu 403 8 binding bind VBG cord-014597-66vd2mdu 403 9 affinity affinity NN cord-014597-66vd2mdu 403 10 for for IN cord-014597-66vd2mdu 403 11 both both CC cord-014597-66vd2mdu 403 12 TUR01 TUR01 NNP cord-014597-66vd2mdu 403 13 and and CC cord-014597-66vd2mdu 403 14 originator originator NN cord-014597-66vd2mdu 403 15 were be VBD cord-014597-66vd2mdu 403 16 highly highly RB cord-014597-66vd2mdu 403 17 similar similar JJ cord-014597-66vd2mdu 403 18 and and CC cord-014597-66vd2mdu 403 19 similarity similarity NN cord-014597-66vd2mdu 403 20 score score NN cord-014597-66vd2mdu 403 21 was be VBD cord-014597-66vd2mdu 403 22 calculated calculate VBN cord-014597-66vd2mdu 403 23 greater great JJR cord-014597-66vd2mdu 403 24 than than IN cord-014597-66vd2mdu 403 25 99 99 CD cord-014597-66vd2mdu 403 26 % % NN cord-014597-66vd2mdu 403 27 , , , cord-014597-66vd2mdu 403 28 as as IN cord-014597-66vd2mdu 403 29 shown show VBN cord-014597-66vd2mdu 403 30 in in IN cord-014597-66vd2mdu 403 31 Fig Fig NNP cord-014597-66vd2mdu 403 32 . . . cord-014597-66vd2mdu 404 1 1b 1b LS cord-014597-66vd2mdu 404 2 . . . cord-014597-66vd2mdu 405 1 In in IN cord-014597-66vd2mdu 405 2 this this DT cord-014597-66vd2mdu 405 3 study study NN cord-014597-66vd2mdu 405 4 , , , cord-014597-66vd2mdu 405 5 state state NN cord-014597-66vd2mdu 405 6 - - HYPH cord-014597-66vd2mdu 405 7 of of IN cord-014597-66vd2mdu 405 8 - - HYPH cord-014597-66vd2mdu 405 9 art art NN cord-014597-66vd2mdu 405 10 analytical analytical JJ cord-014597-66vd2mdu 405 11 techniques technique NNS cord-014597-66vd2mdu 405 12 were be VBD cord-014597-66vd2mdu 405 13 used use VBN cord-014597-66vd2mdu 405 14 to to TO cord-014597-66vd2mdu 405 15 assess assess VB cord-014597-66vd2mdu 405 16 the the DT cord-014597-66vd2mdu 405 17 biosimilarity biosimilarity NN cord-014597-66vd2mdu 405 18 of of IN cord-014597-66vd2mdu 405 19 TUR01 TUR01 NNP cord-014597-66vd2mdu 405 20 to to IN cord-014597-66vd2mdu 405 21 the the DT cord-014597-66vd2mdu 405 22 originator originator NN cord-014597-66vd2mdu 405 23 adalimumab adalimumab NNS cord-014597-66vd2mdu 405 24 . . . cord-014597-66vd2mdu 406 1 Head Head NNP cord-014597-66vd2mdu 406 2 - - HYPH cord-014597-66vd2mdu 406 3 tohead tohead JJ cord-014597-66vd2mdu 406 4 comparison comparison NN cord-014597-66vd2mdu 406 5 data datum NNS cord-014597-66vd2mdu 406 6 clearly clearly RB cord-014597-66vd2mdu 406 7 demonstrated demonstrate VBD cord-014597-66vd2mdu 406 8 that that IN cord-014597-66vd2mdu 406 9 TUR01 TUR01 NNP cord-014597-66vd2mdu 406 10 is be VBZ cord-014597-66vd2mdu 406 11 highly highly RB cord-014597-66vd2mdu 406 12 similar similar JJ cord-014597-66vd2mdu 406 13 to to IN cord-014597-66vd2mdu 406 14 the the DT cord-014597-66vd2mdu 406 15 originator originator NN cord-014597-66vd2mdu 406 16 adalimumab adalimumab NNS cord-014597-66vd2mdu 406 17 in in IN cord-014597-66vd2mdu 406 18 terms term NNS cord-014597-66vd2mdu 406 19 of of IN cord-014597-66vd2mdu 406 20 physicochemical physicochemical JJ cord-014597-66vd2mdu 406 21 and and CC cord-014597-66vd2mdu 406 22 functional functional JJ cord-014597-66vd2mdu 406 23 characteristics characteristic NNS cord-014597-66vd2mdu 406 24 . . . cord-014597-66vd2mdu 407 1 Based base VBN cord-014597-66vd2mdu 407 2 on on IN cord-014597-66vd2mdu 407 3 the the DT cord-014597-66vd2mdu 407 4 analytical analytical JJ cord-014597-66vd2mdu 407 5 similarities similarity NNS cord-014597-66vd2mdu 407 6 , , , cord-014597-66vd2mdu 407 7 we -PRON- PRP cord-014597-66vd2mdu 407 8 . . . cord-014597-66vd2mdu 408 1 Process process NN cord-014597-66vd2mdu 408 2 performance performance NN cord-014597-66vd2mdu 408 3 of of IN cord-014597-66vd2mdu 408 4 basal basal NN cord-014597-66vd2mdu 408 5 medium medium NN cord-014597-66vd2mdu 408 6 ( ( -LRB- cord-014597-66vd2mdu 408 7 black black JJ cord-014597-66vd2mdu 408 8 ) ) -RRB- cord-014597-66vd2mdu 408 9 and and CC cord-014597-66vd2mdu 408 10 feed feed NN cord-014597-66vd2mdu 408 11 - - HYPH cord-014597-66vd2mdu 408 12 spiked spiked JJ cord-014597-66vd2mdu 408 13 ( ( -LRB- cord-014597-66vd2mdu 408 14 red red JJ cord-014597-66vd2mdu 408 15 ) ) -RRB- cord-014597-66vd2mdu 408 16 bioreactor bioreactor NN cord-014597-66vd2mdu 408 17 batch batch NN cord-014597-66vd2mdu 408 18 cultures culture NNS cord-014597-66vd2mdu 408 19 : : : cord-014597-66vd2mdu 408 20 a a DT cord-014597-66vd2mdu 408 21 cell cell NN cord-014597-66vd2mdu 408 22 concentrations concentration NNS cord-014597-66vd2mdu 408 23 and and CC cord-014597-66vd2mdu 408 24 viability viability NN cord-014597-66vd2mdu 408 25 , , , cord-014597-66vd2mdu 408 26 b b LS cord-014597-66vd2mdu 408 27 viable viable JJ cord-014597-66vd2mdu 408 28 cumulative cumulative JJ cord-014597-66vd2mdu 408 29 cell cell NN cord-014597-66vd2mdu 408 30 days day NNS cord-014597-66vd2mdu 408 31 and and CC cord-014597-66vd2mdu 408 32 specific specific JJ cord-014597-66vd2mdu 408 33 growth growth NN cord-014597-66vd2mdu 408 34 rate rate NN cord-014597-66vd2mdu 408 35 , , , cord-014597-66vd2mdu 408 36 and and CC cord-014597-66vd2mdu 408 37 c c NN cord-014597-66vd2mdu 408 38 antibody antibody NN cord-014597-66vd2mdu 408 39 concentrations concentration NNS cord-014597-66vd2mdu 408 40 and and CC cord-014597-66vd2mdu 408 41 cell cell NN cord-014597-66vd2mdu 408 42 - - HYPH cord-014597-66vd2mdu 408 43 specific specific JJ cord-014597-66vd2mdu 408 44 productivity productivity NN cord-014597-66vd2mdu 408 45 . . . cord-014597-66vd2mdu 409 1 Error error NN cord-014597-66vd2mdu 409 2 bars bar NNS cord-014597-66vd2mdu 409 3 indicate indicate VBP cord-014597-66vd2mdu 409 4 standard standard JJ cord-014597-66vd2mdu 409 5 deviation deviation NN cord-014597-66vd2mdu 409 6 from from IN cord-014597-66vd2mdu 409 7 three three CD cord-014597-66vd2mdu 409 8 independent independent JJ cord-014597-66vd2mdu 409 9 experiments experiment NNS cord-014597-66vd2mdu 409 10 . . . cord-014597-66vd2mdu 410 1 The the DT cord-014597-66vd2mdu 410 2 black black JJ cord-014597-66vd2mdu 410 3 arrows arrow NNS cord-014597-66vd2mdu 410 4 on on IN cord-014597-66vd2mdu 410 5 Day Day NNP cord-014597-66vd2mdu 410 6 4 4 CD cord-014597-66vd2mdu 410 7 indicate indicate VBP cord-014597-66vd2mdu 410 8 the the DT cord-014597-66vd2mdu 410 9 beginning beginning NN cord-014597-66vd2mdu 410 10 of of IN cord-014597-66vd2mdu 410 11 decreasing decrease VBG cord-014597-66vd2mdu 410 12 cell cell NN cord-014597-66vd2mdu 410 13 - - HYPH cord-014597-66vd2mdu 410 14 specific specific JJ cord-014597-66vd2mdu 410 15 productivities productivity NNS cord-014597-66vd2mdu 410 16 and and CC cord-014597-66vd2mdu 410 17 lower low JJR cord-014597-66vd2mdu 410 18 cell cell NN cord-014597-66vd2mdu 410 19 - - HYPH cord-014597-66vd2mdu 410 20 specific specific JJ cord-014597-66vd2mdu 410 21 growth growth NN cord-014597-66vd2mdu 410 22 rates rate NNS cord-014597-66vd2mdu 410 23 in in IN cord-014597-66vd2mdu 410 24 basal basal NN cord-014597-66vd2mdu 410 25 medium medium NN cord-014597-66vd2mdu 410 26 cultures culture NNS cord-014597-66vd2mdu 410 27 believe believe VBP cord-014597-66vd2mdu 410 28 that that IN cord-014597-66vd2mdu 410 29 TUR01 TUR01 NNP cord-014597-66vd2mdu 410 30 will will MD cord-014597-66vd2mdu 410 31 have have VB cord-014597-66vd2mdu 410 32 comparable comparable JJ cord-014597-66vd2mdu 410 33 PK PK NNP cord-014597-66vd2mdu 410 34 / / SYM cord-014597-66vd2mdu 410 35 PD PD NNP cord-014597-66vd2mdu 410 36 , , , cord-014597-66vd2mdu 410 37 potency potency NN cord-014597-66vd2mdu 410 38 , , , cord-014597-66vd2mdu 410 39 and and CC cord-014597-66vd2mdu 410 40 efficacy efficacy NN cord-014597-66vd2mdu 410 41 results result NNS cord-014597-66vd2mdu 410 42 to to IN cord-014597-66vd2mdu 410 43 the the DT cord-014597-66vd2mdu 410 44 originator originator NN cord-014597-66vd2mdu 410 45 adalimumab adalimumab NNS cord-014597-66vd2mdu 410 46 . . . cord-014597-66vd2mdu 411 1 The the DT cord-014597-66vd2mdu 411 2 expanded expand VBN cord-014597-66vd2mdu 411 3 interest interest NN cord-014597-66vd2mdu 411 4 in in IN cord-014597-66vd2mdu 411 5 intensified intensify VBN cord-014597-66vd2mdu 411 6 continuous continuous JJ cord-014597-66vd2mdu 411 7 bioprocessing bioprocessing NN cord-014597-66vd2mdu 411 8 has have VBZ cord-014597-66vd2mdu 411 9 highlighted highlight VBN cord-014597-66vd2mdu 411 10 the the DT cord-014597-66vd2mdu 411 11 need need NN cord-014597-66vd2mdu 411 12 to to TO cord-014597-66vd2mdu 411 13 develop develop VB cord-014597-66vd2mdu 411 14 a a DT cord-014597-66vd2mdu 411 15 small small JJ cord-014597-66vd2mdu 411 16 scale scale NN cord-014597-66vd2mdu 411 17 model model NN cord-014597-66vd2mdu 411 18 for for IN cord-014597-66vd2mdu 411 19 perfusion perfusion NN cord-014597-66vd2mdu 411 20 cell cell NN cord-014597-66vd2mdu 411 21 culture culture NN cord-014597-66vd2mdu 411 22 . . . cord-014597-66vd2mdu 412 1 The the DT cord-014597-66vd2mdu 412 2 direction direction NN cord-014597-66vd2mdu 412 3 in in IN cord-014597-66vd2mdu 412 4 the the DT cord-014597-66vd2mdu 412 5 industry industry NN cord-014597-66vd2mdu 412 6 has have VBZ cord-014597-66vd2mdu 412 7 been be VBN cord-014597-66vd2mdu 412 8 to to TO cord-014597-66vd2mdu 412 9 increase increase VB cord-014597-66vd2mdu 412 10 target target NN cord-014597-66vd2mdu 412 11 cell cell NN cord-014597-66vd2mdu 412 12 densities density NNS cord-014597-66vd2mdu 412 13 to to IN cord-014597-66vd2mdu 412 14 ≥50x10 ≥50x10 NN cord-014597-66vd2mdu 412 15 6 6 CD cord-014597-66vd2mdu 412 16 vc vc NNP cord-014597-66vd2mdu 412 17 / / SYM cord-014597-66vd2mdu 412 18 mL ml NN cord-014597-66vd2mdu 412 19 and and CC cord-014597-66vd2mdu 412 20 decrease decrease VB cord-014597-66vd2mdu 412 21 perfusion perfusion NN cord-014597-66vd2mdu 412 22 rates rate NNS cord-014597-66vd2mdu 412 23 to to IN cord-014597-66vd2mdu 412 24 ≤3vvd ≤3vvd NNP cord-014597-66vd2mdu 412 25 . . . cord-014597-66vd2mdu 413 1 In in IN cord-014597-66vd2mdu 413 2 order order NN cord-014597-66vd2mdu 413 3 to to TO cord-014597-66vd2mdu 413 4 increase increase VB cord-014597-66vd2mdu 413 5 the the DT cord-014597-66vd2mdu 413 6 throughput throughput NN cord-014597-66vd2mdu 413 7 of of IN cord-014597-66vd2mdu 413 8 our -PRON- PRP$ cord-014597-66vd2mdu 413 9 perfusion perfusion NN cord-014597-66vd2mdu 413 10 media media NN cord-014597-66vd2mdu 413 11 development development NN cord-014597-66vd2mdu 413 12 capabilities capability NNS cord-014597-66vd2mdu 413 13 we -PRON- PRP cord-014597-66vd2mdu 413 14 sought seek VBD cord-014597-66vd2mdu 413 15 to to TO cord-014597-66vd2mdu 413 16 develop develop VB cord-014597-66vd2mdu 413 17 a a DT cord-014597-66vd2mdu 413 18 small small JJ cord-014597-66vd2mdu 413 19 scale scale NN cord-014597-66vd2mdu 413 20 model model NN cord-014597-66vd2mdu 413 21 of of IN cord-014597-66vd2mdu 413 22 perfusion perfusion NN cord-014597-66vd2mdu 413 23 using use VBG cord-014597-66vd2mdu 413 24 the the DT cord-014597-66vd2mdu 413 25 ambr ambr NNP cord-014597-66vd2mdu 413 26 ® ® NN cord-014597-66vd2mdu 413 27 15 15 CD cord-014597-66vd2mdu 413 28 instrument instrument NN cord-014597-66vd2mdu 413 29 ( ( -LRB- cord-014597-66vd2mdu 413 30 Sartorius Sartorius NNP cord-014597-66vd2mdu 413 31 , , , cord-014597-66vd2mdu 413 32 Germany Germany NNP cord-014597-66vd2mdu 413 33 ) ) -RRB- cord-014597-66vd2mdu 413 34 . . . cord-014597-66vd2mdu 414 1 We -PRON- PRP cord-014597-66vd2mdu 414 2 used use VBD cord-014597-66vd2mdu 414 3 a a DT cord-014597-66vd2mdu 414 4 modified modify VBN cord-014597-66vd2mdu 414 5 cell cell NN cord-014597-66vd2mdu 414 6 settling settling NN cord-014597-66vd2mdu 414 7 model model NN cord-014597-66vd2mdu 414 8 from from IN cord-014597-66vd2mdu 414 9 the the DT cord-014597-66vd2mdu 414 10 previously previously RB cord-014597-66vd2mdu 414 11 published publish VBN cord-014597-66vd2mdu 414 12 by by IN cord-014597-66vd2mdu 414 13 Kreye Kreye NNP cord-014597-66vd2mdu 414 14 et et NNP cord-014597-66vd2mdu 414 15 . . . cord-014597-66vd2mdu 415 1 al al NNP cord-014597-66vd2mdu 415 2 . . . cord-014597-66vd2mdu 416 1 to to TO cord-014597-66vd2mdu 416 2 achieve achieve VB cord-014597-66vd2mdu 416 3 the the DT cord-014597-66vd2mdu 416 4 cell cell NN cord-014597-66vd2mdu 416 5 retention retention NN cord-014597-66vd2mdu 416 6 necessary necessary JJ cord-014597-66vd2mdu 416 7 to to TO cord-014597-66vd2mdu 416 8 reach reach VB cord-014597-66vd2mdu 416 9 perfusion perfusion NN cord-014597-66vd2mdu 416 10 relevant relevant JJ cord-014597-66vd2mdu 416 11 viable viable JJ cord-014597-66vd2mdu 416 12 cell cell NN cord-014597-66vd2mdu 416 13 concentrations concentration NNS cord-014597-66vd2mdu 416 14 [ [ -LRB- cord-014597-66vd2mdu 416 15 1 1 CD cord-014597-66vd2mdu 416 16 ] ] -RRB- cord-014597-66vd2mdu 416 17 . . . cord-014597-66vd2mdu 417 1 In in IN cord-014597-66vd2mdu 417 2 this this DT cord-014597-66vd2mdu 417 3 work work NN cord-014597-66vd2mdu 417 4 , , , cord-014597-66vd2mdu 417 5 we -PRON- PRP cord-014597-66vd2mdu 417 6 will will MD cord-014597-66vd2mdu 417 7 show show VB cord-014597-66vd2mdu 417 8 the the DT cord-014597-66vd2mdu 417 9 application application NN cord-014597-66vd2mdu 417 10 of of IN cord-014597-66vd2mdu 417 11 this this DT cord-014597-66vd2mdu 417 12 small small JJ cord-014597-66vd2mdu 417 13 scale scale NN cord-014597-66vd2mdu 417 14 model model NN cord-014597-66vd2mdu 417 15 for for IN cord-014597-66vd2mdu 417 16 : : : cord-014597-66vd2mdu 418 1 ( ( -LRB- cord-014597-66vd2mdu 418 2 1 1 LS cord-014597-66vd2mdu 418 3 ) ) -RRB- cord-014597-66vd2mdu 418 4 Identification identification NN cord-014597-66vd2mdu 418 5 of of IN cord-014597-66vd2mdu 418 6 specific specific JJ cord-014597-66vd2mdu 418 7 productivity productivity NN cord-014597-66vd2mdu 418 8 performance performance NN cord-014597-66vd2mdu 418 9 over over IN cord-014597-66vd2mdu 418 10 a a DT cord-014597-66vd2mdu 418 11 steady steady JJ cord-014597-66vd2mdu 418 12 - - HYPH cord-014597-66vd2mdu 418 13 state state NN cord-014597-66vd2mdu 418 14 for for IN cord-014597-66vd2mdu 418 15 tested test VBN cord-014597-66vd2mdu 418 16 media medium NNS cord-014597-66vd2mdu 418 17 , , , cord-014597-66vd2mdu 418 18 ( ( -LRB- cord-014597-66vd2mdu 418 19 2 2 LS cord-014597-66vd2mdu 418 20 ) ) -RRB- cord-014597-66vd2mdu 418 21 Identification identification NN cord-014597-66vd2mdu 418 22 of of IN cord-014597-66vd2mdu 418 23 CSPR CSPR NNP cord-014597-66vd2mdu 418 24 min min NNP cord-014597-66vd2mdu 418 25 for for IN cord-014597-66vd2mdu 418 26 a a DT cord-014597-66vd2mdu 418 27 specific specific JJ cord-014597-66vd2mdu 418 28 cell cell NN cord-014597-66vd2mdu 418 29 line line NN cord-014597-66vd2mdu 418 30 and and CC cord-014597-66vd2mdu 418 31 medium medium NN cord-014597-66vd2mdu 418 32 combination combination NN cord-014597-66vd2mdu 418 33 , , , cord-014597-66vd2mdu 418 34 and and CC cord-014597-66vd2mdu 418 35 ( ( -LRB- cord-014597-66vd2mdu 418 36 3 3 LS cord-014597-66vd2mdu 418 37 ) ) -RRB- cord-014597-66vd2mdu 418 38 Confirmation confirmation NN cord-014597-66vd2mdu 418 39 of of IN cord-014597-66vd2mdu 418 40 consistent consistent JJ cord-014597-66vd2mdu 418 41 product product NN cord-014597-66vd2mdu 418 42 quality quality NN cord-014597-66vd2mdu 418 43 profiles profile NNS cord-014597-66vd2mdu 418 44 between between IN cord-014597-66vd2mdu 418 45 the the DT cord-014597-66vd2mdu 418 46 small small JJ cord-014597-66vd2mdu 418 47 scale scale NN cord-014597-66vd2mdu 418 48 model model NN cord-014597-66vd2mdu 418 49 and and CC cord-014597-66vd2mdu 418 50 benchtop benchtop NN cord-014597-66vd2mdu 418 51 perfusion perfusion NN cord-014597-66vd2mdu 418 52 ( ( -LRB- cord-014597-66vd2mdu 418 53 data datum NNS cord-014597-66vd2mdu 418 54 not not RB cord-014597-66vd2mdu 418 55 shown show VBN cord-014597-66vd2mdu 418 56 ) ) -RRB- cord-014597-66vd2mdu 418 57 . . . cord-014597-66vd2mdu 419 1 A a DT cord-014597-66vd2mdu 419 2 CHOZN CHOZN NNP cord-014597-66vd2mdu 419 3 ® ® JJ cord-014597-66vd2mdu 419 4 cell cell NN cord-014597-66vd2mdu 419 5 line line NN cord-014597-66vd2mdu 419 6 producing produce VBG cord-014597-66vd2mdu 419 7 an an DT cord-014597-66vd2mdu 419 8 IgG1 igg1 NN cord-014597-66vd2mdu 419 9 was be VBD cord-014597-66vd2mdu 419 10 evaluated evaluate VBN cord-014597-66vd2mdu 419 11 in in IN cord-014597-66vd2mdu 419 12 several several JJ cord-014597-66vd2mdu 419 13 proprietary proprietary JJ cord-014597-66vd2mdu 419 14 chemically chemically RB cord-014597-66vd2mdu 419 15 defined define VBN cord-014597-66vd2mdu 419 16 media medium NNS cord-014597-66vd2mdu 419 17 prototypes prototype NNS cord-014597-66vd2mdu 419 18 generated generate VBN cord-014597-66vd2mdu 419 19 during during IN cord-014597-66vd2mdu 419 20 the the DT cord-014597-66vd2mdu 419 21 development development NN cord-014597-66vd2mdu 419 22 of of IN cord-014597-66vd2mdu 419 23 the the DT cord-014597-66vd2mdu 419 24 catalog catalog NN cord-014597-66vd2mdu 419 25 EXCELL EXCELL NNP cord-014597-66vd2mdu 420 1 ® ® , cord-014597-66vd2mdu 420 2 Advanced advanced JJ cord-014597-66vd2mdu 420 3 HD HD NNP cord-014597-66vd2mdu 420 4 Perfusion Perfusion NNP cord-014597-66vd2mdu 420 5 medium medium NN cord-014597-66vd2mdu 420 6 : : : cord-014597-66vd2mdu 420 7 " " `` cord-014597-66vd2mdu 420 8 Fed Fed NNP cord-014597-66vd2mdu 420 9 Batch Batch NNP cord-014597-66vd2mdu 420 10 Medium Medium NNP cord-014597-66vd2mdu 420 11 " " '' cord-014597-66vd2mdu 420 12 , , , cord-014597-66vd2mdu 420 13 " " `` cord-014597-66vd2mdu 420 14 Early Early NNP cord-014597-66vd2mdu 420 15 Prototype Prototype NNP cord-014597-66vd2mdu 420 16 " " '' cord-014597-66vd2mdu 420 17 , , , cord-014597-66vd2mdu 420 18 " " `` cord-014597-66vd2mdu 420 19 Mid Mid NNP cord-014597-66vd2mdu 420 20 Prototype Prototype NNP cord-014597-66vd2mdu 420 21 " " '' cord-014597-66vd2mdu 420 22 , , , cord-014597-66vd2mdu 420 23 " " `` cord-014597-66vd2mdu 420 24 Intermediate Intermediate NNP cord-014597-66vd2mdu 420 25 Prototype Prototype NNP cord-014597-66vd2mdu 420 26 " " '' cord-014597-66vd2mdu 420 27 and and CC cord-014597-66vd2mdu 420 28 " " `` cord-014597-66vd2mdu 420 29 Late Late NNP cord-014597-66vd2mdu 420 30 Prototype Prototype NNP cord-014597-66vd2mdu 420 31 " " '' cord-014597-66vd2mdu 420 32 [ [ -LRB- cord-014597-66vd2mdu 420 33 2 2 CD cord-014597-66vd2mdu 420 34 ] ] -RRB- cord-014597-66vd2mdu 420 35 . . . cord-014597-66vd2mdu 421 1 Small small JJ cord-014597-66vd2mdu 421 2 scale scale NN cord-014597-66vd2mdu 421 3 simulation simulation NN cord-014597-66vd2mdu 421 4 of of IN cord-014597-66vd2mdu 421 5 perfusion perfusion NN cord-014597-66vd2mdu 421 6 experiments experiment NNS cord-014597-66vd2mdu 421 7 were be VBD cord-014597-66vd2mdu 421 8 run run VBN cord-014597-66vd2mdu 421 9 in in IN cord-014597-66vd2mdu 421 10 ambr ambr NNP cord-014597-66vd2mdu 421 11 ® ® NNP cord-014597-66vd2mdu 421 12 15 15 CD cord-014597-66vd2mdu 421 13 . . . cord-014597-66vd2mdu 422 1 Media Media NNP cord-014597-66vd2mdu 422 2 exchange exchange NN cord-014597-66vd2mdu 422 3 was be VBD cord-014597-66vd2mdu 422 4 performed perform VBN cord-014597-66vd2mdu 422 5 3 3 CD cord-014597-66vd2mdu 422 6 times time NNS cord-014597-66vd2mdu 422 7 per per IN cord-014597-66vd2mdu 422 8 day day NN cord-014597-66vd2mdu 422 9 in in IN cord-014597-66vd2mdu 422 10 equal equal JJ cord-014597-66vd2mdu 422 11 amounts amount NNS cord-014597-66vd2mdu 422 12 . . . cord-014597-66vd2mdu 423 1 Agitation agitation NN cord-014597-66vd2mdu 423 2 , , , cord-014597-66vd2mdu 423 3 gassing gassing NN cord-014597-66vd2mdu 423 4 , , , cord-014597-66vd2mdu 423 5 and and CC cord-014597-66vd2mdu 423 6 liquid liquid JJ cord-014597-66vd2mdu 423 7 handling handling NN cord-014597-66vd2mdu 423 8 were be VBD cord-014597-66vd2mdu 423 9 stopped stop VBN cord-014597-66vd2mdu 423 10 for for IN cord-014597-66vd2mdu 423 11 an an DT cord-014597-66vd2mdu 423 12 optimized optimized JJ cord-014597-66vd2mdu 423 13 period period NN cord-014597-66vd2mdu 423 14 of of IN cord-014597-66vd2mdu 423 15 time time NN cord-014597-66vd2mdu 423 16 to to TO cord-014597-66vd2mdu 423 17 allow allow VB cord-014597-66vd2mdu 423 18 cells cell NNS cord-014597-66vd2mdu 423 19 to to TO cord-014597-66vd2mdu 423 20 settle settle VB cord-014597-66vd2mdu 423 21 to to IN cord-014597-66vd2mdu 423 22 the the DT cord-014597-66vd2mdu 423 23 bottom bottom NN cord-014597-66vd2mdu 423 24 . . . cord-014597-66vd2mdu 424 1 Spent spend VBN cord-014597-66vd2mdu 424 2 media medium NNS cord-014597-66vd2mdu 424 3 was be VBD cord-014597-66vd2mdu 424 4 removed remove VBN cord-014597-66vd2mdu 424 5 in in IN cord-014597-66vd2mdu 424 6 an an DT cord-014597-66vd2mdu 424 7 amount amount NN cord-014597-66vd2mdu 424 8 proportional proportional JJ cord-014597-66vd2mdu 424 9 to to IN cord-014597-66vd2mdu 424 10 1/3 1/3 DT cord-014597-66vd2mdu 424 11 rd rd NNP cord-014597-66vd2mdu 424 12 daily daily NNP cord-014597-66vd2mdu 424 13 exchange exchange NN cord-014597-66vd2mdu 424 14 volume volume NN cord-014597-66vd2mdu 424 15 . . . cord-014597-66vd2mdu 425 1 Agitation agitation NN cord-014597-66vd2mdu 425 2 , , , cord-014597-66vd2mdu 425 3 gassing gassing NN cord-014597-66vd2mdu 425 4 , , , cord-014597-66vd2mdu 425 5 and and CC cord-014597-66vd2mdu 425 6 liquid liquid JJ cord-014597-66vd2mdu 425 7 handling handling NN cord-014597-66vd2mdu 425 8 were be VBD cord-014597-66vd2mdu 425 9 resumed resume VBN cord-014597-66vd2mdu 425 10 and and CC cord-014597-66vd2mdu 425 11 fresh fresh JJ cord-014597-66vd2mdu 425 12 media medium NNS cord-014597-66vd2mdu 425 13 was be VBD cord-014597-66vd2mdu 425 14 added add VBN cord-014597-66vd2mdu 425 15 back back RB cord-014597-66vd2mdu 425 16 to to IN cord-014597-66vd2mdu 425 17 the the DT cord-014597-66vd2mdu 425 18 vessels vessel NNS cord-014597-66vd2mdu 425 19 . . . cord-014597-66vd2mdu 426 1 For for IN cord-014597-66vd2mdu 426 2 benchtop benchtop NN cord-014597-66vd2mdu 426 3 perfusion perfusion NN cord-014597-66vd2mdu 426 4 , , , cord-014597-66vd2mdu 426 5 cells cell NNS cord-014597-66vd2mdu 426 6 were be VBD cord-014597-66vd2mdu 426 7 inoculated inoculate VBN cord-014597-66vd2mdu 426 8 in in IN cord-014597-66vd2mdu 426 9 3L 3l CD cord-014597-66vd2mdu 426 10 Applikon Applikon NNP cord-014597-66vd2mdu 426 11 bioreactors bioreactor NNS cord-014597-66vd2mdu 426 12 ( ( -LRB- cord-014597-66vd2mdu 426 13 Applikon Applikon NNP cord-014597-66vd2mdu 426 14 , , , cord-014597-66vd2mdu 426 15 Netherlands Netherlands NNP cord-014597-66vd2mdu 426 16 ) ) -RRB- cord-014597-66vd2mdu 426 17 . . . cord-014597-66vd2mdu 427 1 At at IN cord-014597-66vd2mdu 427 2 a a DT cord-014597-66vd2mdu 427 3 concentration concentration NN cord-014597-66vd2mdu 427 4 of~6.0x10 of~6.0x10 NNP cord-014597-66vd2mdu 427 5 6 6 CD cord-014597-66vd2mdu 427 6 vc vc NNP cord-014597-66vd2mdu 427 7 / / SYM cord-014597-66vd2mdu 427 8 mL ml NN cord-014597-66vd2mdu 427 9 , , , cord-014597-66vd2mdu 427 10 perfusion perfusion NN cord-014597-66vd2mdu 427 11 was be VBD cord-014597-66vd2mdu 427 12 initiated initiate VBN cord-014597-66vd2mdu 427 13 using use VBG cord-014597-66vd2mdu 427 14 the the DT cord-014597-66vd2mdu 427 15 ATF2 ATF2 NNP cord-014597-66vd2mdu 427 16 ( ( -LRB- cord-014597-66vd2mdu 427 17 RepliGen RepliGen NNP cord-014597-66vd2mdu 427 18 , , , cord-014597-66vd2mdu 427 19 Massachusetts Massachusetts NNP cord-014597-66vd2mdu 427 20 ) ) -RRB- cord-014597-66vd2mdu 427 21 . . . cord-014597-66vd2mdu 428 1 Perfusion perfusion NN cord-014597-66vd2mdu 428 2 rate rate NN cord-014597-66vd2mdu 428 3 was be VBD cord-014597-66vd2mdu 428 4 limited limit VBN cord-014597-66vd2mdu 428 5 at at IN cord-014597-66vd2mdu 428 6 1.2vvd 1.2vvd CD cord-014597-66vd2mdu 428 7 during during IN cord-014597-66vd2mdu 428 8 steady steady JJ cord-014597-66vd2mdu 428 9 - - HYPH cord-014597-66vd2mdu 428 10 state state NN cord-014597-66vd2mdu 428 11 . . . cord-014597-66vd2mdu 429 1 Using use VBG cord-014597-66vd2mdu 429 2 the the DT cord-014597-66vd2mdu 429 3 cell cell NN cord-014597-66vd2mdu 429 4 settling settling NN cord-014597-66vd2mdu 429 5 method method NN cord-014597-66vd2mdu 429 6 described describe VBN cord-014597-66vd2mdu 429 7 above above IN cord-014597-66vd2mdu 429 8 we -PRON- PRP cord-014597-66vd2mdu 429 9 have have VBP cord-014597-66vd2mdu 429 10 been be VBN cord-014597-66vd2mdu 429 11 able able JJ cord-014597-66vd2mdu 429 12 to to TO cord-014597-66vd2mdu 429 13 achieve achieve VB cord-014597-66vd2mdu 429 14 ≥90 ≥90 NNP cord-014597-66vd2mdu 429 15 % % NN cord-014597-66vd2mdu 429 16 cell cell NN cord-014597-66vd2mdu 429 17 retention retention NN cord-014597-66vd2mdu 429 18 efficiency efficiency NN cord-014597-66vd2mdu 429 19 . . . cord-014597-66vd2mdu 430 1 All all DT cord-014597-66vd2mdu 430 2 media medium NNS cord-014597-66vd2mdu 430 3 tested test VBN cord-014597-66vd2mdu 430 4 in in IN cord-014597-66vd2mdu 430 5 this this DT cord-014597-66vd2mdu 430 6 work work NN cord-014597-66vd2mdu 430 7 were be VBD cord-014597-66vd2mdu 430 8 able able JJ cord-014597-66vd2mdu 430 9 to to TO cord-014597-66vd2mdu 430 10 reach reach VB cord-014597-66vd2mdu 430 11 and and CC cord-014597-66vd2mdu 430 12 maintain maintain VB cord-014597-66vd2mdu 430 13 the the DT cord-014597-66vd2mdu 430 14 30x10 30x10 CD cord-014597-66vd2mdu 430 15 6 6 CD cord-014597-66vd2mdu 430 16 vc vc NNP cord-014597-66vd2mdu 430 17 / / SYM cord-014597-66vd2mdu 430 18 mL ml NN cord-014597-66vd2mdu 430 19 target target NN cord-014597-66vd2mdu 430 20 cell cell NN cord-014597-66vd2mdu 430 21 density density NN cord-014597-66vd2mdu 430 22 at at IN cord-014597-66vd2mdu 430 23 1vvd 1vvd CD cord-014597-66vd2mdu 431 1 ( ( -LRB- cord-014597-66vd2mdu 431 2 Fig Fig NNP cord-014597-66vd2mdu 431 3 . . NNP cord-014597-66vd2mdu 431 4 1 1 CD cord-014597-66vd2mdu 431 5 ) ) -RRB- cord-014597-66vd2mdu 431 6 . . . cord-014597-66vd2mdu 432 1 Performance performance NN cord-014597-66vd2mdu 432 2 of of IN cord-014597-66vd2mdu 432 3 each each DT cord-014597-66vd2mdu 432 4 media medium NNS cord-014597-66vd2mdu 432 5 formulation formulation NN cord-014597-66vd2mdu 432 6 was be VBD cord-014597-66vd2mdu 432 7 ranked rank VBN cord-014597-66vd2mdu 432 8 based base VBN cord-014597-66vd2mdu 432 9 on on IN cord-014597-66vd2mdu 432 10 specific specific JJ cord-014597-66vd2mdu 432 11 productivity productivity NN cord-014597-66vd2mdu 432 12 ( ( -LRB- cord-014597-66vd2mdu 432 13 Table table NN cord-014597-66vd2mdu 432 14 1 1 CD cord-014597-66vd2mdu 432 15 ) ) -RRB- cord-014597-66vd2mdu 432 16 . . . cord-014597-66vd2mdu 433 1 Using use VBG cord-014597-66vd2mdu 433 2 " " `` cord-014597-66vd2mdu 433 3 Intermediate Intermediate NNP cord-014597-66vd2mdu 433 4 Prototype Prototype NNP cord-014597-66vd2mdu 433 5 " " '' cord-014597-66vd2mdu 433 6 , , , cord-014597-66vd2mdu 433 7 minimum minimum JJ cord-014597-66vd2mdu 433 8 steady steady JJ cord-014597-66vd2mdu 433 9 - - HYPH cord-014597-66vd2mdu 433 10 state state NN cord-014597-66vd2mdu 433 11 CSPR CSPR NNP cord-014597-66vd2mdu 433 12 was be VBD cord-014597-66vd2mdu 433 13 determined determine VBN cord-014597-66vd2mdu 433 14 to to TO cord-014597-66vd2mdu 433 15 be be VB cord-014597-66vd2mdu 433 16 33.3pL 33.3pl CD cord-014597-66vd2mdu 433 17 / / SYM cord-014597-66vd2mdu 433 18 c c NN cord-014597-66vd2mdu 433 19 / / SYM cord-014597-66vd2mdu 433 20 d d NN cord-014597-66vd2mdu 433 21 for for IN cord-014597-66vd2mdu 433 22 this this DT cord-014597-66vd2mdu 433 23 cell cell NN cord-014597-66vd2mdu 433 24 line line NN cord-014597-66vd2mdu 433 25 . . . cord-014597-66vd2mdu 434 1 N n CD cord-014597-66vd2mdu 434 2 - - HYPH cord-014597-66vd2mdu 434 3 glycan glycan NN cord-014597-66vd2mdu 434 4 analysis analysis NN cord-014597-66vd2mdu 434 5 of of IN cord-014597-66vd2mdu 434 6 ambr ambr NNP cord-014597-66vd2mdu 434 7 ® ® NNP cord-014597-66vd2mdu 434 8 15 15 CD cord-014597-66vd2mdu 434 9 and and CC cord-014597-66vd2mdu 434 10 bioreactor bioreactor NN cord-014597-66vd2mdu 434 11 samples sample NNS cord-014597-66vd2mdu 434 12 via via IN cord-014597-66vd2mdu 434 13 intact intact JJ cord-014597-66vd2mdu 434 14 mass mass NN cord-014597-66vd2mdu 434 15 spectrometry spectrometry NN cord-014597-66vd2mdu 434 16 displayed display VBN cord-014597-66vd2mdu 434 17 only only RB cord-014597-66vd2mdu 434 18 slight slight JJ cord-014597-66vd2mdu 434 19 differences difference NNS cord-014597-66vd2mdu 434 20 in in IN cord-014597-66vd2mdu 434 21 product product NN cord-014597-66vd2mdu 434 22 quality quality NN cord-014597-66vd2mdu 434 23 profile profile NN cord-014597-66vd2mdu 434 24 ( ( -LRB- cord-014597-66vd2mdu 434 25 data datum NNS cord-014597-66vd2mdu 434 26 not not RB cord-014597-66vd2mdu 434 27 shown show VBN cord-014597-66vd2mdu 434 28 ) ) -RRB- cord-014597-66vd2mdu 434 29 . . . cord-014597-66vd2mdu 435 1 Our -PRON- PRP$ cord-014597-66vd2mdu 435 2 work work NN cord-014597-66vd2mdu 435 3 has have VBZ cord-014597-66vd2mdu 435 4 shown show VBN cord-014597-66vd2mdu 435 5 a a DT cord-014597-66vd2mdu 435 6 clear clear JJ cord-014597-66vd2mdu 435 7 distinction distinction NN cord-014597-66vd2mdu 435 8 between between IN cord-014597-66vd2mdu 435 9 various various JJ cord-014597-66vd2mdu 435 10 prototype prototype NN cord-014597-66vd2mdu 435 11 perfusion perfusion NN cord-014597-66vd2mdu 435 12 media medium NNS cord-014597-66vd2mdu 435 13 and and CC cord-014597-66vd2mdu 435 14 demonstrated demonstrate VBD cord-014597-66vd2mdu 435 15 a a DT cord-014597-66vd2mdu 435 16 50 50 CD cord-014597-66vd2mdu 435 17 % % NN cord-014597-66vd2mdu 435 18 increase increase NN cord-014597-66vd2mdu 435 19 in in IN cord-014597-66vd2mdu 435 20 specific specific JJ cord-014597-66vd2mdu 435 21 productivity productivity NN cord-014597-66vd2mdu 435 22 over over IN cord-014597-66vd2mdu 435 23 " " `` cord-014597-66vd2mdu 435 24 Fed Fed NNP cord-014597-66vd2mdu 435 25 Batch Batch NNP cord-014597-66vd2mdu 435 26 Medium Medium NNP cord-014597-66vd2mdu 435 27 " " '' cord-014597-66vd2mdu 435 28 used use VBN cord-014597-66vd2mdu 435 29 in in IN cord-014597-66vd2mdu 435 30 perfusion perfusion NN cord-014597-66vd2mdu 435 31 . . . cord-014597-66vd2mdu 436 1 Additionally additionally RB cord-014597-66vd2mdu 436 2 , , , cord-014597-66vd2mdu 436 3 we -PRON- PRP cord-014597-66vd2mdu 436 4 have have VBP cord-014597-66vd2mdu 436 5 shown show VBN cord-014597-66vd2mdu 436 6 the the DT cord-014597-66vd2mdu 436 7 application application NN cord-014597-66vd2mdu 436 8 to to TO cord-014597-66vd2mdu 436 9 further further RB cord-014597-66vd2mdu 436 10 characterize characterize VB cord-014597-66vd2mdu 436 11 the the DT cord-014597-66vd2mdu 436 12 process process NN cord-014597-66vd2mdu 436 13 using use VBG cord-014597-66vd2mdu 436 14 this this DT cord-014597-66vd2mdu 436 15 model model NN cord-014597-66vd2mdu 436 16 to to TO cord-014597-66vd2mdu 436 17 determine determine VB cord-014597-66vd2mdu 436 18 CSPR CSPR NNP cord-014597-66vd2mdu 436 19 min min NNP cord-014597-66vd2mdu 436 20 for for IN cord-014597-66vd2mdu 436 21 a a DT cord-014597-66vd2mdu 436 22 given give VBN cord-014597-66vd2mdu 436 23 medium medium NN cord-014597-66vd2mdu 436 24 and and CC cord-014597-66vd2mdu 436 25 cell cell NN cord-014597-66vd2mdu 436 26 line line NN cord-014597-66vd2mdu 436 27 . . . cord-014597-66vd2mdu 437 1 The the DT cord-014597-66vd2mdu 437 2 transient transient JJ cord-014597-66vd2mdu 437 3 process process NN cord-014597-66vd2mdu 437 4 has have VBZ cord-014597-66vd2mdu 437 5 been be VBN cord-014597-66vd2mdu 437 6 successfully successfully RB cord-014597-66vd2mdu 437 7 operated operate VBN cord-014597-66vd2mdu 437 8 at at IN cord-014597-66vd2mdu 437 9 500L 500l CD cord-014597-66vd2mdu 437 10 in in IN cord-014597-66vd2mdu 437 11 a a DT cord-014597-66vd2mdu 437 12 Sartorius Sartorius NNP cord-014597-66vd2mdu 437 13 Biostat Biostat NNP cord-014597-66vd2mdu 437 14 Single single JJ cord-014597-66vd2mdu 437 15 Use Use NNP cord-014597-66vd2mdu 437 16 Bioreactor Bioreactor NNP cord-014597-66vd2mdu 437 17 ( ( -LRB- cord-014597-66vd2mdu 437 18 SUB SUB NNP cord-014597-66vd2mdu 437 19 ) ) -RRB- cord-014597-66vd2mdu 437 20 , , , cord-014597-66vd2mdu 437 21 yielding yield VBG cord-014597-66vd2mdu 437 22 0.4 0.4 CD cord-014597-66vd2mdu 437 23 kg kg NNS cord-014597-66vd2mdu 437 24 of of IN cord-014597-66vd2mdu 437 25 crude crude JJ cord-014597-66vd2mdu 437 26 product product NN cord-014597-66vd2mdu 437 27 from from IN cord-014597-66vd2mdu 437 28 a a DT cord-014597-66vd2mdu 437 29 two two CD cord-014597-66vd2mdu 437 30 - - HYPH cord-014597-66vd2mdu 437 31 week week NN cord-014597-66vd2mdu 437 32 expression expression NN cord-014597-66vd2mdu 437 33 culture culture NN cord-014597-66vd2mdu 437 34 ( ( -LRB- cord-014597-66vd2mdu 437 35 Table table NN cord-014597-66vd2mdu 437 36 1 1 CD cord-014597-66vd2mdu 437 37 ) ) -RRB- cord-014597-66vd2mdu 437 38 . . . cord-014597-66vd2mdu 438 1 Successful successful JJ cord-014597-66vd2mdu 438 2 scale scale NN cord-014597-66vd2mdu 438 3 up up RP cord-014597-66vd2mdu 438 4 of of IN cord-014597-66vd2mdu 438 5 the the DT cord-014597-66vd2mdu 438 6 process process NN cord-014597-66vd2mdu 438 7 to to IN cord-014597-66vd2mdu 438 8 500L 500L NNP cord-014597-66vd2mdu 438 9 creates create VBZ cord-014597-66vd2mdu 438 10 the the DT cord-014597-66vd2mdu 438 11 potential potential NN cord-014597-66vd2mdu 438 12 to to TO cord-014597-66vd2mdu 438 13 supply supply VB cord-014597-66vd2mdu 438 14 transiently transiently RB cord-014597-66vd2mdu 438 15 expressed express VBN cord-014597-66vd2mdu 438 16 products product NNS cord-014597-66vd2mdu 438 17 to to TO cord-014597-66vd2mdu 438 18 support support VB cord-014597-66vd2mdu 438 19 toxicology toxicology NN cord-014597-66vd2mdu 438 20 studies study NNS cord-014597-66vd2mdu 438 21 or or CC cord-014597-66vd2mdu 438 22 even even RB cord-014597-66vd2mdu 438 23 early early JJ cord-014597-66vd2mdu 438 24 GMP GMP NNP cord-014597-66vd2mdu 438 25 clinical clinical JJ cord-014597-66vd2mdu 438 26 supply supply NN cord-014597-66vd2mdu 438 27 , , , cord-014597-66vd2mdu 438 28 enabling enable VBG cord-014597-66vd2mdu 438 29 accelerated accelerate VBN cord-014597-66vd2mdu 438 30 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 438 31 development development NN cord-014597-66vd2mdu 438 32 project project NN cord-014597-66vd2mdu 438 33 timelines timeline NNS cord-014597-66vd2mdu 438 34 . . . cord-014597-66vd2mdu 439 1 The the DT cord-014597-66vd2mdu 439 2 scale scale NN cord-014597-66vd2mdu 439 3 up up RP cord-014597-66vd2mdu 439 4 from from IN cord-014597-66vd2mdu 439 5 rocking rock VBG cord-014597-66vd2mdu 439 6 bioreactors bioreactor NNS cord-014597-66vd2mdu 439 7 ( ( -LRB- cord-014597-66vd2mdu 439 8 RBr rbr NN cord-014597-66vd2mdu 439 9 ) ) -RRB- cord-014597-66vd2mdu 439 10 to to TO cord-014597-66vd2mdu 439 11 SUB sub VB cord-014597-66vd2mdu 439 12 scale scale NN cord-014597-66vd2mdu 439 13 identified identify VBD cord-014597-66vd2mdu 439 14 some some DT cord-014597-66vd2mdu 439 15 scalability scalability NN cord-014597-66vd2mdu 439 16 issues issue NNS cord-014597-66vd2mdu 439 17 . . . cord-014597-66vd2mdu 440 1 Lower lower VB cord-014597-66vd2mdu 440 2 specific specific JJ cord-014597-66vd2mdu 440 3 productivity productivity NN cord-014597-66vd2mdu 440 4 due due JJ cord-014597-66vd2mdu 440 5 to to IN cord-014597-66vd2mdu 440 6 increased increase VBN cord-014597-66vd2mdu 440 7 cell cell NN cord-014597-66vd2mdu 440 8 growth growth NN cord-014597-66vd2mdu 440 9 and and CC cord-014597-66vd2mdu 440 10 decreased decrease VBD cord-014597-66vd2mdu 440 11 titres titre NNS cord-014597-66vd2mdu 440 12 were be VBD cord-014597-66vd2mdu 440 13 observed observe VBN cord-014597-66vd2mdu 440 14 in in IN cord-014597-66vd2mdu 440 15 the the DT cord-014597-66vd2mdu 440 16 SUB sub NN cord-014597-66vd2mdu 441 1 ( ( -LRB- cord-014597-66vd2mdu 441 2 Fig Fig NNP cord-014597-66vd2mdu 441 3 . . NNP cord-014597-66vd2mdu 441 4 1 1 CD cord-014597-66vd2mdu 441 5 iii iii NNP cord-014597-66vd2mdu 441 6 & & CC cord-014597-66vd2mdu 441 7 iv iv NNP cord-014597-66vd2mdu 441 8 ) ) -RRB- cord-014597-66vd2mdu 441 9 . . . cord-014597-66vd2mdu 442 1 To to TO cord-014597-66vd2mdu 442 2 improve improve VB cord-014597-66vd2mdu 442 3 the the DT cord-014597-66vd2mdu 442 4 predictability predictability NN cord-014597-66vd2mdu 442 5 of of IN cord-014597-66vd2mdu 442 6 scale scale NN cord-014597-66vd2mdu 442 7 up up RP cord-014597-66vd2mdu 442 8 , , , cord-014597-66vd2mdu 442 9 a a DT cord-014597-66vd2mdu 442 10 new new JJ cord-014597-66vd2mdu 442 11 process process NN cord-014597-66vd2mdu 442 12 was be VBD cord-014597-66vd2mdu 442 13 developed develop VBN cord-014597-66vd2mdu 442 14 and and CC cord-014597-66vd2mdu 442 15 evaluated evaluate VBN cord-014597-66vd2mdu 442 16 in in IN cord-014597-66vd2mdu 442 17 the the DT cord-014597-66vd2mdu 442 18 SUB sub NN cord-014597-66vd2mdu 442 19 vessels vessel NNS cord-014597-66vd2mdu 442 20 utilising utilise VBG cord-014597-66vd2mdu 442 21 a a DT cord-014597-66vd2mdu 442 22 modified modify VBN cord-014597-66vd2mdu 442 23 transfection transfection NN cord-014597-66vd2mdu 442 24 method method NN cord-014597-66vd2mdu 442 25 , , , cord-014597-66vd2mdu 442 26 which which WDT cord-014597-66vd2mdu 442 27 resulted result VBD cord-014597-66vd2mdu 442 28 in in IN cord-014597-66vd2mdu 442 29 comparable comparable JJ cord-014597-66vd2mdu 442 30 expression expression NN cord-014597-66vd2mdu 442 31 levels level NNS cord-014597-66vd2mdu 442 32 and and CC cord-014597-66vd2mdu 442 33 specific specific JJ cord-014597-66vd2mdu 442 34 productivity productivity NN cord-014597-66vd2mdu 442 35 between between IN cord-014597-66vd2mdu 442 36 RBr rbr NN cord-014597-66vd2mdu 442 37 and and CC cord-014597-66vd2mdu 442 38 SUB sub NN cord-014597-66vd2mdu 442 39 scales scale NNS cord-014597-66vd2mdu 442 40 . . . cord-014597-66vd2mdu 443 1 Two two CD cord-014597-66vd2mdu 443 2 sets set NNS cord-014597-66vd2mdu 443 3 of of IN cord-014597-66vd2mdu 443 4 expression expression NN cord-014597-66vd2mdu 443 5 vectors vector NNS cord-014597-66vd2mdu 443 6 comprising comprise VBG cord-014597-66vd2mdu 443 7 heavy heavy JJ cord-014597-66vd2mdu 443 8 chain chain NN cord-014597-66vd2mdu 443 9 and and CC cord-014597-66vd2mdu 443 10 light light NN cord-014597-66vd2mdu 443 11 chain chain NN cord-014597-66vd2mdu 443 12 plasmids plasmid NNS cord-014597-66vd2mdu 443 13 expressing express VBG cord-014597-66vd2mdu 443 14 a a DT cord-014597-66vd2mdu 443 15 human human JJ cord-014597-66vd2mdu 443 16 IgG1 IgG1 NNP cord-014597-66vd2mdu 443 17 kappa kappa NN cord-014597-66vd2mdu 443 18 mAb mAb NNP cord-014597-66vd2mdu 443 19 , , , cord-014597-66vd2mdu 443 20 as as IN cord-014597-66vd2mdu 443 21 previously previously RB cord-014597-66vd2mdu 443 22 described describe VBN cord-014597-66vd2mdu 443 23 [ [ -LRB- cord-014597-66vd2mdu 443 24 1 1 CD cord-014597-66vd2mdu 443 25 , , , cord-014597-66vd2mdu 443 26 2 2 CD cord-014597-66vd2mdu 443 27 ] ] -RRB- cord-014597-66vd2mdu 443 28 were be VBD cord-014597-66vd2mdu 443 29 used use VBN cord-014597-66vd2mdu 443 30 in in IN cord-014597-66vd2mdu 443 31 the the DT cord-014597-66vd2mdu 443 32 process process NN cord-014597-66vd2mdu 443 33 optimisation optimisation NN cord-014597-66vd2mdu 443 34 study study NN cord-014597-66vd2mdu 443 35 . . . cord-014597-66vd2mdu 444 1 The the DT cord-014597-66vd2mdu 444 2 cell cell NN cord-014597-66vd2mdu 444 3 line line NN cord-014597-66vd2mdu 444 4 used use VBN cord-014597-66vd2mdu 444 5 for for IN cord-014597-66vd2mdu 444 6 transient transient JJ cord-014597-66vd2mdu 444 7 expression expression NN cord-014597-66vd2mdu 444 8 and and CC cord-014597-66vd2mdu 444 9 the the DT cord-014597-66vd2mdu 444 10 PEI PEI NNP cord-014597-66vd2mdu 444 11 mediated mediate VBD cord-014597-66vd2mdu 444 12 transfection transfection NN cord-014597-66vd2mdu 444 13 method method NN cord-014597-66vd2mdu 444 14 has have VBZ cord-014597-66vd2mdu 444 15 been be VBN cord-014597-66vd2mdu 444 16 described describe VBN cord-014597-66vd2mdu 444 17 previously previously RB cord-014597-66vd2mdu 444 18 [ [ -LRB- cord-014597-66vd2mdu 444 19 1 1 CD cord-014597-66vd2mdu 444 20 ] ] -RRB- cord-014597-66vd2mdu 444 21 . . . cord-014597-66vd2mdu 445 1 Transfected transfecte VBN cord-014597-66vd2mdu 445 2 cultures culture NNS cord-014597-66vd2mdu 445 3 were be VBD cord-014597-66vd2mdu 445 4 run run VBN cord-014597-66vd2mdu 445 5 under under IN cord-014597-66vd2mdu 445 6 fed fed NNP cord-014597-66vd2mdu 445 7 batch batch NN cord-014597-66vd2mdu 445 8 conditions condition NNS cord-014597-66vd2mdu 445 9 for for IN cord-014597-66vd2mdu 445 10 14 14 CD cord-014597-66vd2mdu 445 11 days day NNS cord-014597-66vd2mdu 445 12 in in IN cord-014597-66vd2mdu 445 13 22L 22L NNP cord-014597-66vd2mdu 445 14 GE GE NNP cord-014597-66vd2mdu 445 15 Healthcare Healthcare NNP cord-014597-66vd2mdu 445 16 Wave Wave NNP cord-014597-66vd2mdu 445 17 bioreactors bioreactor NNS cord-014597-66vd2mdu 445 18 ( ( -LRB- cord-014597-66vd2mdu 445 19 RBr RBr NNP cord-014597-66vd2mdu 445 20 ) ) -RRB- cord-014597-66vd2mdu 445 21 , , , cord-014597-66vd2mdu 445 22 Hyclone Hyclone NNP cord-014597-66vd2mdu 445 23 SUB SUB NNP cord-014597-66vd2mdu 445 24 using use VBG cord-014597-66vd2mdu 445 25 50L 50l CD cord-014597-66vd2mdu 445 26 and and CC cord-014597-66vd2mdu 445 27 250L 250l CD cord-014597-66vd2mdu 445 28 Hyclone Hyclone NNP cord-014597-66vd2mdu 445 29 bioreactor bioreactor NN cord-014597-66vd2mdu 445 30 bags bag NNS cord-014597-66vd2mdu 445 31 ( ( -LRB- cord-014597-66vd2mdu 445 32 Thermo Thermo NNP cord-014597-66vd2mdu 445 33 Scientific Scientific NNP cord-014597-66vd2mdu 445 34 ) ) -RRB- cord-014597-66vd2mdu 445 35 . . . cord-014597-66vd2mdu 446 1 The the DT cord-014597-66vd2mdu 446 2 transfection transfection NN cord-014597-66vd2mdu 446 3 process process NN cord-014597-66vd2mdu 446 4 was be VBD cord-014597-66vd2mdu 446 5 modified modify VBN cord-014597-66vd2mdu 446 6 to to TO cord-014597-66vd2mdu 446 7 address address VB cord-014597-66vd2mdu 446 8 the the DT cord-014597-66vd2mdu 446 9 reduced reduced JJ cord-014597-66vd2mdu 446 10 titres titre NNS cord-014597-66vd2mdu 446 11 and and CC cord-014597-66vd2mdu 446 12 higher high JJR cord-014597-66vd2mdu 446 13 viable viable JJ cord-014597-66vd2mdu 446 14 cell cell NN cord-014597-66vd2mdu 446 15 density density NN cord-014597-66vd2mdu 446 16 ( ( -LRB- cord-014597-66vd2mdu 446 17 VCD vcd NN cord-014597-66vd2mdu 446 18 ) ) -RRB- cord-014597-66vd2mdu 446 19 seen see VBN cord-014597-66vd2mdu 446 20 in in IN cord-014597-66vd2mdu 446 21 the the DT cord-014597-66vd2mdu 446 22 SUB sub NN cord-014597-66vd2mdu 446 23 cultures culture NNS cord-014597-66vd2mdu 446 24 . . . cord-014597-66vd2mdu 447 1 Shake shake VB cord-014597-66vd2mdu 447 2 flask flask NN cord-014597-66vd2mdu 447 3 cultures culture NNS cord-014597-66vd2mdu 447 4 were be VBD cord-014597-66vd2mdu 447 5 used use VBN cord-014597-66vd2mdu 447 6 to to TO cord-014597-66vd2mdu 447 7 assess assess VB cord-014597-66vd2mdu 447 8 the the DT cord-014597-66vd2mdu 447 9 standard standard NN cord-014597-66vd2mdu 447 10 ( ( -LRB- cord-014597-66vd2mdu 447 11 A a NN cord-014597-66vd2mdu 447 12 ) ) -RRB- cord-014597-66vd2mdu 447 13 and and CC cord-014597-66vd2mdu 447 14 modified modify VBN cord-014597-66vd2mdu 447 15 transfection transfection NN cord-014597-66vd2mdu 447 16 processes process NNS cord-014597-66vd2mdu 447 17 ( ( -LRB- cord-014597-66vd2mdu 447 18 B b NN cord-014597-66vd2mdu 447 19 and and CC cord-014597-66vd2mdu 447 20 C C NNP cord-014597-66vd2mdu 447 21 ) ) -RRB- cord-014597-66vd2mdu 447 22 ( ( -LRB- cord-014597-66vd2mdu 447 23 Fig fig NN cord-014597-66vd2mdu 447 24 . . . cord-014597-66vd2mdu 448 1 1 1 LS cord-014597-66vd2mdu 448 2 , , , cord-014597-66vd2mdu 448 3 i i NNP cord-014597-66vd2mdu 448 4 & & CC cord-014597-66vd2mdu 448 5 ii ii NNP cord-014597-66vd2mdu 448 6 ) ) -RRB- cord-014597-66vd2mdu 448 7 . . . cord-014597-66vd2mdu 449 1 Process process NN cord-014597-66vd2mdu 449 2 C C NNP cord-014597-66vd2mdu 449 3 was be VBD cord-014597-66vd2mdu 449 4 identified identify VBN cord-014597-66vd2mdu 449 5 as as IN cord-014597-66vd2mdu 449 6 the the DT cord-014597-66vd2mdu 449 7 process process NN cord-014597-66vd2mdu 449 8 to to TO cord-014597-66vd2mdu 449 9 be be VB cord-014597-66vd2mdu 449 10 studied study VBN cord-014597-66vd2mdu 449 11 at at IN cord-014597-66vd2mdu 449 12 SUB sub NN cord-014597-66vd2mdu 449 13 scale scale NN cord-014597-66vd2mdu 449 14 , , , cord-014597-66vd2mdu 449 15 offering offer VBG cord-014597-66vd2mdu 449 16 the the DT cord-014597-66vd2mdu 449 17 potential potential NN cord-014597-66vd2mdu 449 18 to to TO cord-014597-66vd2mdu 449 19 mitigate mitigate VB cord-014597-66vd2mdu 449 20 the the DT cord-014597-66vd2mdu 449 21 high high JJ cord-014597-66vd2mdu 449 22 viable viable JJ cord-014597-66vd2mdu 449 23 cell cell NN cord-014597-66vd2mdu 449 24 densities density NNS cord-014597-66vd2mdu 449 25 ( ( -LRB- cord-014597-66vd2mdu 449 26 VCD VCD NNP cord-014597-66vd2mdu 449 27 ) ) -RRB- cord-014597-66vd2mdu 449 28 observed observe VBD cord-014597-66vd2mdu 449 29 . . . cord-014597-66vd2mdu 450 1 Scaling scale VBG cord-014597-66vd2mdu 450 2 up up RP cord-014597-66vd2mdu 450 3 process process NN cord-014597-66vd2mdu 450 4 C c NN cord-014597-66vd2mdu 450 5 to to IN cord-014597-66vd2mdu 450 6 50L 50l CD cord-014597-66vd2mdu 450 7 and and CC cord-014597-66vd2mdu 450 8 250L 250l CD cord-014597-66vd2mdu 451 1 SUB SUB NNP cord-014597-66vd2mdu 451 2 resulted result VBD cord-014597-66vd2mdu 451 3 in in IN cord-014597-66vd2mdu 451 4 cultures culture NNS cord-014597-66vd2mdu 451 5 producing produce VBG cord-014597-66vd2mdu 451 6 titres titre NNS cord-014597-66vd2mdu 451 7 exceeding exceed VBG cord-014597-66vd2mdu 451 8 1g 1g CD cord-014597-66vd2mdu 451 9 / / SYM cord-014597-66vd2mdu 451 10 L l NN cord-014597-66vd2mdu 451 11 with with IN cord-014597-66vd2mdu 451 12 desired desire VBN cord-014597-66vd2mdu 451 13 cell cell NN cord-014597-66vd2mdu 451 14 growth growth NN cord-014597-66vd2mdu 451 15 profiles profile NNS cord-014597-66vd2mdu 451 16 . . . cord-014597-66vd2mdu 452 1 Scale scale VB cord-014597-66vd2mdu 452 2 up up RP cord-014597-66vd2mdu 452 3 of of IN cord-014597-66vd2mdu 452 4 process process NN cord-014597-66vd2mdu 452 5 A a NN cord-014597-66vd2mdu 452 6 into into IN cord-014597-66vd2mdu 452 7 SUB sub NN cord-014597-66vd2mdu 452 8 vessels vessel NNS cord-014597-66vd2mdu 452 9 resulted result VBN cord-014597-66vd2mdu 452 10 in in IN cord-014597-66vd2mdu 452 11 decreased decreased JJ cord-014597-66vd2mdu 452 12 productivity productivity NN cord-014597-66vd2mdu 452 13 compared compare VBN cord-014597-66vd2mdu 452 14 to to IN cord-014597-66vd2mdu 452 15 the the DT cord-014597-66vd2mdu 452 16 RBr rbr NN cord-014597-66vd2mdu 452 17 scale scale NN cord-014597-66vd2mdu 452 18 . . . cord-014597-66vd2mdu 453 1 After after IN cord-014597-66vd2mdu 453 2 optimisation optimisation NN cord-014597-66vd2mdu 453 3 , , , cord-014597-66vd2mdu 453 4 the the DT cord-014597-66vd2mdu 453 5 SUB sub NN cord-014597-66vd2mdu 453 6 process process NN cord-014597-66vd2mdu 453 7 C c NN cord-014597-66vd2mdu 453 8 yielded yield VBD cord-014597-66vd2mdu 453 9 increased increase VBN cord-014597-66vd2mdu 453 10 specific specific JJ cord-014597-66vd2mdu 453 11 productivities productivity NNS cord-014597-66vd2mdu 453 12 and and CC cord-014597-66vd2mdu 453 13 expression expression NN cord-014597-66vd2mdu 453 14 titres titre NNS cord-014597-66vd2mdu 453 15 comparable comparable JJ cord-014597-66vd2mdu 453 16 to to IN cord-014597-66vd2mdu 453 17 those those DT cord-014597-66vd2mdu 453 18 seen see VBN cord-014597-66vd2mdu 453 19 at at IN cord-014597-66vd2mdu 453 20 RBr rbr NN cord-014597-66vd2mdu 453 21 scale scale NN cord-014597-66vd2mdu 453 22 ( ( -LRB- cord-014597-66vd2mdu 453 23 Table table NN cord-014597-66vd2mdu 453 24 1 1 CD cord-014597-66vd2mdu 453 25 ) ) -RRB- cord-014597-66vd2mdu 453 26 . . . cord-014597-66vd2mdu 454 1 MedImmune MedImmune NNP cord-014597-66vd2mdu 454 2 has have VBZ cord-014597-66vd2mdu 454 3 successfully successfully RB cord-014597-66vd2mdu 454 4 completed complete VBN cord-014597-66vd2mdu 454 5 the the DT cord-014597-66vd2mdu 454 6 first first RB cord-014597-66vd2mdu 454 7 known known JJ cord-014597-66vd2mdu 454 8 successful successful JJ cord-014597-66vd2mdu 454 9 CHO CHO NNP cord-014597-66vd2mdu 454 10 transient transient JJ cord-014597-66vd2mdu 454 11 culture culture NN cord-014597-66vd2mdu 454 12 at at IN cord-014597-66vd2mdu 454 13 500L 500l CD cord-014597-66vd2mdu 454 14 scale scale NN cord-014597-66vd2mdu 454 15 producing produce VBG cord-014597-66vd2mdu 454 16 > > XX cord-014597-66vd2mdu 454 17 800mg 800mg NNP cord-014597-66vd2mdu 454 18 / / SYM cord-014597-66vd2mdu 454 19 L l NN cord-014597-66vd2mdu 454 20 of of IN cord-014597-66vd2mdu 454 21 mAb mab NN cord-014597-66vd2mdu 454 22 at at IN cord-014597-66vd2mdu 454 23 harvest harvest NN cord-014597-66vd2mdu 454 24 . . . cord-014597-66vd2mdu 455 1 Process process NN cord-014597-66vd2mdu 455 2 optimisation optimisation NN cord-014597-66vd2mdu 455 3 has have VBZ cord-014597-66vd2mdu 455 4 subsequently subsequently RB cord-014597-66vd2mdu 455 5 demonstrated demonstrate VBN cord-014597-66vd2mdu 455 6 reproducible reproducible JJ cord-014597-66vd2mdu 455 7 titres titre NNS cord-014597-66vd2mdu 455 8 at at IN cord-014597-66vd2mdu 455 9 50L 50l CD cord-014597-66vd2mdu 455 10 to to IN cord-014597-66vd2mdu 455 11 250L 250l CD cord-014597-66vd2mdu 455 12 scale scale VB cord-014597-66vd2mdu 455 13 exceeding exceed VBG cord-014597-66vd2mdu 455 14 1g 1g CD cord-014597-66vd2mdu 455 15 / / SYM cord-014597-66vd2mdu 455 16 L l NN cord-014597-66vd2mdu 455 17 with with IN cord-014597-66vd2mdu 455 18 comparable comparable JJ cord-014597-66vd2mdu 455 19 glycosylation glycosylation NN cord-014597-66vd2mdu 455 20 profiles profile NNS cord-014597-66vd2mdu 455 21 between between IN cord-014597-66vd2mdu 455 22 SUB sub NN cord-014597-66vd2mdu 455 23 and and CC cord-014597-66vd2mdu 455 24 RBr rbr NN cord-014597-66vd2mdu 455 25 cultures culture NNS cord-014597-66vd2mdu 455 26 across across IN cord-014597-66vd2mdu 455 27 scales scale NNS cord-014597-66vd2mdu 455 28 . . . cord-014597-66vd2mdu 456 1 Comprehensive comprehensive JJ cord-014597-66vd2mdu 456 2 analysis analysis NN cord-014597-66vd2mdu 456 3 of of IN cord-014597-66vd2mdu 456 4 the the DT cord-014597-66vd2mdu 456 5 impact impact NN cord-014597-66vd2mdu 456 6 of of IN cord-014597-66vd2mdu 456 7 trace trace NN cord-014597-66vd2mdu 456 8 elements element NNS cord-014597-66vd2mdu 456 9 in in IN cord-014597-66vd2mdu 456 10 media medium NNS cord-014597-66vd2mdu 456 11 on on IN cord-014597-66vd2mdu 456 12 clone clone NN cord-014597-66vd2mdu 456 13 dependent dependent JJ cord-014597-66vd2mdu 456 14 process process NN cord-014597-66vd2mdu 456 15 performance performance NN cord-014597-66vd2mdu 456 16 and and CC cord-014597-66vd2mdu 456 17 product product NN cord-014597-66vd2mdu 456 18 quality quality NN cord-014597-66vd2mdu 456 19 Background Background NNP cord-014597-66vd2mdu 456 20 State State NNP cord-014597-66vd2mdu 456 21 - - HYPH cord-014597-66vd2mdu 456 22 of of IN cord-014597-66vd2mdu 456 23 - - HYPH cord-014597-66vd2mdu 456 24 the the DT cord-014597-66vd2mdu 456 25 - - HYPH cord-014597-66vd2mdu 456 26 art art NN cord-014597-66vd2mdu 456 27 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 456 28 processes process NNS cord-014597-66vd2mdu 456 29 are be VBP cord-014597-66vd2mdu 456 30 accounting account VBG cord-014597-66vd2mdu 456 31 concomitantly concomitantly RB cord-014597-66vd2mdu 456 32 for for IN cord-014597-66vd2mdu 456 33 process process NN cord-014597-66vd2mdu 456 34 performance performance NN cord-014597-66vd2mdu 456 35 and and CC cord-014597-66vd2mdu 456 36 product product NN cord-014597-66vd2mdu 456 37 quality quality NN cord-014597-66vd2mdu 456 38 . . . cord-014597-66vd2mdu 457 1 Even even RB cord-014597-66vd2mdu 457 2 though though IN cord-014597-66vd2mdu 457 3 high high JJ cord-014597-66vd2mdu 457 4 yielding yielding JJ cord-014597-66vd2mdu 457 5 , , , cord-014597-66vd2mdu 457 6 robust robust JJ cord-014597-66vd2mdu 457 7 processes process NNS cord-014597-66vd2mdu 457 8 are be VBP cord-014597-66vd2mdu 457 9 the the DT cord-014597-66vd2mdu 457 10 cornerstones cornerstone NNS cord-014597-66vd2mdu 457 11 of of IN cord-014597-66vd2mdu 457 12 any any DT cord-014597-66vd2mdu 457 13 process process NN cord-014597-66vd2mdu 457 14 development development NN cord-014597-66vd2mdu 457 15 , , , cord-014597-66vd2mdu 457 16 product product NN cord-014597-66vd2mdu 457 17 quality quality NN cord-014597-66vd2mdu 457 18 parameters parameter NNS cord-014597-66vd2mdu 457 19 such such JJ cord-014597-66vd2mdu 457 20 as as IN cord-014597-66vd2mdu 457 21 structural structural JJ cord-014597-66vd2mdu 457 22 integrity integrity NN cord-014597-66vd2mdu 457 23 , , , cord-014597-66vd2mdu 457 24 charge charge NN cord-014597-66vd2mdu 457 25 variances variance NNS cord-014597-66vd2mdu 457 26 and and CC cord-014597-66vd2mdu 457 27 post post JJ cord-014597-66vd2mdu 457 28 - - JJ cord-014597-66vd2mdu 457 29 translational translational JJ cord-014597-66vd2mdu 457 30 modifications modification NNS cord-014597-66vd2mdu 457 31 are be VBP cord-014597-66vd2mdu 457 32 progressively progressively RB cord-014597-66vd2mdu 457 33 becoming become VBG cord-014597-66vd2mdu 457 34 the the DT cord-014597-66vd2mdu 457 35 focus focus NN cord-014597-66vd2mdu 457 36 of of IN cord-014597-66vd2mdu 457 37 the the DT cord-014597-66vd2mdu 457 38 developmental developmental JJ cord-014597-66vd2mdu 457 39 work work NN cord-014597-66vd2mdu 457 40 . . . cord-014597-66vd2mdu 458 1 In in IN cord-014597-66vd2mdu 458 2 conjunction conjunction NN cord-014597-66vd2mdu 458 3 with with IN cord-014597-66vd2mdu 458 4 host host NN cord-014597-66vd2mdu 458 5 cell cell NN cord-014597-66vd2mdu 458 6 line line NN cord-014597-66vd2mdu 458 7 selection selection NN cord-014597-66vd2mdu 458 8 and and CC cord-014597-66vd2mdu 458 9 process process NN cord-014597-66vd2mdu 458 10 performance performance NN cord-014597-66vd2mdu 458 11 parameters parameter NNS cord-014597-66vd2mdu 458 12 , , , cord-014597-66vd2mdu 458 13 media medium NNS cord-014597-66vd2mdu 458 14 components component NNS cord-014597-66vd2mdu 458 15 are be VBP cord-014597-66vd2mdu 458 16 crucial crucial JJ cord-014597-66vd2mdu 458 17 for for IN cord-014597-66vd2mdu 458 18 the the DT cord-014597-66vd2mdu 458 19 continued continued JJ cord-014597-66vd2mdu 458 20 progress progress NN cord-014597-66vd2mdu 458 21 in in IN cord-014597-66vd2mdu 458 22 rational rational JJ cord-014597-66vd2mdu 458 23 modulation modulation NN cord-014597-66vd2mdu 458 24 of of IN cord-014597-66vd2mdu 458 25 product product NN cord-014597-66vd2mdu 458 26 quality quality NN cord-014597-66vd2mdu 458 27 attributes attribute VBZ cord-014597-66vd2mdu 458 28 affecting affect VBG cord-014597-66vd2mdu 458 29 biological biological JJ cord-014597-66vd2mdu 458 30 activity activity NN cord-014597-66vd2mdu 458 31 , , , cord-014597-66vd2mdu 458 32 immunogenicity immunogenicity NN cord-014597-66vd2mdu 458 33 , , , cord-014597-66vd2mdu 458 34 half half JJ cord-014597-66vd2mdu 458 35 - - HYPH cord-014597-66vd2mdu 458 36 life life NN cord-014597-66vd2mdu 458 37 or or CC cord-014597-66vd2mdu 458 38 stability stability NN cord-014597-66vd2mdu 458 39 . . . cord-014597-66vd2mdu 459 1 Among among IN cord-014597-66vd2mdu 459 2 media medium NNS cord-014597-66vd2mdu 459 3 components component NNS cord-014597-66vd2mdu 459 4 , , , cord-014597-66vd2mdu 459 5 trace trace NN cord-014597-66vd2mdu 459 6 elements element NNS cord-014597-66vd2mdu 459 7 ( ( -LRB- cord-014597-66vd2mdu 459 8 TE TE NNP cord-014597-66vd2mdu 459 9 ) ) -RRB- cord-014597-66vd2mdu 459 10 are be VBP cord-014597-66vd2mdu 459 11 of of IN cord-014597-66vd2mdu 459 12 particular particular JJ cord-014597-66vd2mdu 459 13 interest interest NN cord-014597-66vd2mdu 459 14 as as IN cord-014597-66vd2mdu 459 15 they -PRON- PRP cord-014597-66vd2mdu 459 16 play play VBP cord-014597-66vd2mdu 459 17 a a DT cord-014597-66vd2mdu 459 18 pivotal pivotal JJ cord-014597-66vd2mdu 459 19 role role NN cord-014597-66vd2mdu 459 20 in in IN cord-014597-66vd2mdu 459 21 various various JJ cord-014597-66vd2mdu 459 22 cell cell NN cord-014597-66vd2mdu 459 23 metabolism metabolism NN cord-014597-66vd2mdu 459 24 pathways pathway NNS cord-014597-66vd2mdu 459 25 . . . cord-014597-66vd2mdu 460 1 Based base VBN cord-014597-66vd2mdu 460 2 on on IN cord-014597-66vd2mdu 460 3 a a DT cord-014597-66vd2mdu 460 4 comprehensive comprehensive JJ cord-014597-66vd2mdu 460 5 DOE DOE NNP cord-014597-66vd2mdu 460 6 approach approach NN cord-014597-66vd2mdu 460 7 , , , cord-014597-66vd2mdu 460 8 extensive extensive JJ cord-014597-66vd2mdu 460 9 process process NN cord-014597-66vd2mdu 460 10 performance performance NN cord-014597-66vd2mdu 460 11 - - : cord-014597-66vd2mdu 460 12 and and CC cord-014597-66vd2mdu 460 13 product product NN cord-014597-66vd2mdu 460 14 quality quality NN cord-014597-66vd2mdu 460 15 evaluation evaluation NN cord-014597-66vd2mdu 460 16 combined combine VBN cord-014597-66vd2mdu 460 17 with with IN cord-014597-66vd2mdu 460 18 metabolic metabolic JJ cord-014597-66vd2mdu 460 19 flux flux NN cord-014597-66vd2mdu 460 20 analysis analysis NN cord-014597-66vd2mdu 460 21 , , , cord-014597-66vd2mdu 460 22 the the DT cord-014597-66vd2mdu 460 23 impact impact NN cord-014597-66vd2mdu 460 24 of of IN cord-014597-66vd2mdu 460 25 several several JJ cord-014597-66vd2mdu 460 26 trace trace NN cord-014597-66vd2mdu 460 27 elements element NNS cord-014597-66vd2mdu 460 28 on on IN cord-014597-66vd2mdu 460 29 the the DT cord-014597-66vd2mdu 460 30 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 460 31 process process NN cord-014597-66vd2mdu 460 32 is be VBZ cord-014597-66vd2mdu 460 33 assessed assess VBN cord-014597-66vd2mdu 460 34 . . . cord-014597-66vd2mdu 461 1 In in IN cord-014597-66vd2mdu 461 2 a a DT cord-014597-66vd2mdu 461 3 comprehensive comprehensive JJ cord-014597-66vd2mdu 461 4 I i NN cord-014597-66vd2mdu 461 5 - - HYPH cord-014597-66vd2mdu 461 6 optimal optimal JJ cord-014597-66vd2mdu 461 7 DOE DOE NNP cord-014597-66vd2mdu 461 8 approach approach NN cord-014597-66vd2mdu 461 9 ( ( -LRB- cord-014597-66vd2mdu 461 10 Fig Fig NNP cord-014597-66vd2mdu 461 11 . . . cord-014597-66vd2mdu 461 12 1 1 CD cord-014597-66vd2mdu 461 13 ) ) -RRB- cord-014597-66vd2mdu 461 14 , , , cord-014597-66vd2mdu 461 15 the the DT cord-014597-66vd2mdu 461 16 effect effect NN cord-014597-66vd2mdu 461 17 of of IN cord-014597-66vd2mdu 461 18 six six CD cord-014597-66vd2mdu 461 19 TE TE NNP cord-014597-66vd2mdu 461 20 in in IN cord-014597-66vd2mdu 461 21 various various JJ cord-014597-66vd2mdu 461 22 concentration concentration NN cord-014597-66vd2mdu 461 23 levels level NNS cord-014597-66vd2mdu 461 24 and and CC cord-014597-66vd2mdu 461 25 combinations combination NNS cord-014597-66vd2mdu 461 26 in in IN cord-014597-66vd2mdu 461 27 serum serum NN cord-014597-66vd2mdu 461 28 - - HYPH cord-014597-66vd2mdu 461 29 free free JJ cord-014597-66vd2mdu 461 30 media medium NNS cord-014597-66vd2mdu 461 31 was be VBD cord-014597-66vd2mdu 461 32 studied study VBN cord-014597-66vd2mdu 461 33 for for IN cord-014597-66vd2mdu 461 34 four four CD cord-014597-66vd2mdu 461 35 different different JJ cord-014597-66vd2mdu 461 36 CHO CHO NNP cord-014597-66vd2mdu 461 37 - - HYPH cord-014597-66vd2mdu 461 38 K1 K1 NNP cord-014597-66vd2mdu 461 39 cells cell NNS cord-014597-66vd2mdu 461 40 lines line NNS cord-014597-66vd2mdu 461 41 in in IN cord-014597-66vd2mdu 461 42 an an DT cord-014597-66vd2mdu 461 43 ambr ambr NNP cord-014597-66vd2mdu 461 44 ® ® NN cord-014597-66vd2mdu 461 45 15 15 CD cord-014597-66vd2mdu 461 46 setup setup NN cord-014597-66vd2mdu 461 47 . . . cord-014597-66vd2mdu 462 1 A a DT cord-014597-66vd2mdu 462 2 scrutiny scrutiny NN cord-014597-66vd2mdu 462 3 of of IN cord-014597-66vd2mdu 462 4 the the DT cord-014597-66vd2mdu 462 5 process process NN cord-014597-66vd2mdu 462 6 performance performance NN cord-014597-66vd2mdu 462 7 parameters parameter NNS cord-014597-66vd2mdu 462 8 such such JJ cord-014597-66vd2mdu 462 9 as as IN cord-014597-66vd2mdu 462 10 cellular cellular JJ cord-014597-66vd2mdu 462 11 growth growth NN cord-014597-66vd2mdu 462 12 , , , cord-014597-66vd2mdu 462 13 productivity productivity NN cord-014597-66vd2mdu 462 14 , , , cord-014597-66vd2mdu 462 15 amino amino JJ cord-014597-66vd2mdu 462 16 acids acid NNS cord-014597-66vd2mdu 462 17 and and CC cord-014597-66vd2mdu 462 18 vitamins vitamin NNS cord-014597-66vd2mdu 462 19 consumptions consumption NNS cord-014597-66vd2mdu 462 20 rates rate NNS cord-014597-66vd2mdu 462 21 for for IN cord-014597-66vd2mdu 462 22 each each DT cord-014597-66vd2mdu 462 23 of of IN cord-014597-66vd2mdu 462 24 the the DT cord-014597-66vd2mdu 462 25 conditions condition NNS cord-014597-66vd2mdu 462 26 was be VBD cord-014597-66vd2mdu 462 27 performed perform VBN cord-014597-66vd2mdu 462 28 . . . cord-014597-66vd2mdu 463 1 The the DT cord-014597-66vd2mdu 463 2 process process NN cord-014597-66vd2mdu 463 3 performance performance NN cord-014597-66vd2mdu 463 4 evaluation evaluation NN cord-014597-66vd2mdu 463 5 was be VBD cord-014597-66vd2mdu 463 6 accompanied accompany VBN cord-014597-66vd2mdu 463 7 by by IN cord-014597-66vd2mdu 463 8 extensive extensive JJ cord-014597-66vd2mdu 463 9 product product NN cord-014597-66vd2mdu 463 10 quality quality NN cord-014597-66vd2mdu 463 11 analysis analysis NN cord-014597-66vd2mdu 463 12 including include VBG cord-014597-66vd2mdu 463 13 size size NN cord-014597-66vd2mdu 463 14 and and CC cord-014597-66vd2mdu 463 15 charge charge NN cord-014597-66vd2mdu 463 16 variants variant NNS cord-014597-66vd2mdu 463 17 , , , cord-014597-66vd2mdu 463 18 glycosylation glycosylation NN cord-014597-66vd2mdu 463 19 patterns pattern NNS cord-014597-66vd2mdu 463 20 , , , cord-014597-66vd2mdu 463 21 oxidation oxidation NN cord-014597-66vd2mdu 463 22 and and CC cord-014597-66vd2mdu 463 23 methylation methylation NN cord-014597-66vd2mdu 463 24 . . . cord-014597-66vd2mdu 464 1 Furthermore furthermore RB cord-014597-66vd2mdu 464 2 , , , cord-014597-66vd2mdu 464 3 a a DT cord-014597-66vd2mdu 464 4 metabolic metabolic JJ cord-014597-66vd2mdu 464 5 flux flux NN cord-014597-66vd2mdu 464 6 analysis analysis NN cord-014597-66vd2mdu 464 7 was be VBD cord-014597-66vd2mdu 464 8 performed perform VBN cord-014597-66vd2mdu 464 9 based base VBN cord-014597-66vd2mdu 464 10 on on IN cord-014597-66vd2mdu 464 11 the the DT cord-014597-66vd2mdu 464 12 nitrogen nitrogen NN cord-014597-66vd2mdu 464 13 balance balance NN cord-014597-66vd2mdu 464 14 . . . cord-014597-66vd2mdu 465 1 Based base VBN cord-014597-66vd2mdu 465 2 on on IN cord-014597-66vd2mdu 465 3 extensive extensive JJ cord-014597-66vd2mdu 465 4 analytical analytical JJ cord-014597-66vd2mdu 465 5 data datum NNS cord-014597-66vd2mdu 465 6 , , , cord-014597-66vd2mdu 465 7 the the DT cord-014597-66vd2mdu 465 8 obtained obtain VBN cord-014597-66vd2mdu 465 9 response response NN cord-014597-66vd2mdu 465 10 surface surface NN cord-014597-66vd2mdu 465 11 model model NN cord-014597-66vd2mdu 465 12 provides provide VBZ cord-014597-66vd2mdu 465 13 a a DT cord-014597-66vd2mdu 465 14 clear clear JJ cord-014597-66vd2mdu 465 15 insight insight NN cord-014597-66vd2mdu 465 16 into into IN cord-014597-66vd2mdu 465 17 the the DT cord-014597-66vd2mdu 465 18 impact impact NN cord-014597-66vd2mdu 465 19 of of IN cord-014597-66vd2mdu 465 20 particular particular JJ cord-014597-66vd2mdu 465 21 TE TE NNP cord-014597-66vd2mdu 465 22 and and CC cord-014597-66vd2mdu 465 23 their -PRON- PRP$ cord-014597-66vd2mdu 465 24 combinations combination NNS cord-014597-66vd2mdu 465 25 on on IN cord-014597-66vd2mdu 465 26 process process NN cord-014597-66vd2mdu 465 27 performance performance NN cord-014597-66vd2mdu 465 28 and and CC cord-014597-66vd2mdu 465 29 product product NN cord-014597-66vd2mdu 465 30 quality quality NN cord-014597-66vd2mdu 465 31 . . . cord-014597-66vd2mdu 466 1 The the DT cord-014597-66vd2mdu 466 2 high high JJ cord-014597-66vd2mdu 466 3 model model NN cord-014597-66vd2mdu 466 4 quality quality NN cord-014597-66vd2mdu 466 5 enables enable VBZ cord-014597-66vd2mdu 466 6 discriminations discrimination NNS cord-014597-66vd2mdu 466 7 between between IN cord-014597-66vd2mdu 466 8 clone clone NN cord-014597-66vd2mdu 466 9 dependent dependent JJ cord-014597-66vd2mdu 466 10 and and CC cord-014597-66vd2mdu 466 11 clone clone VB cord-014597-66vd2mdu 466 12 independent independent JJ cord-014597-66vd2mdu 466 13 effects effect NNS cord-014597-66vd2mdu 466 14 . . . cord-014597-66vd2mdu 467 1 With with IN cord-014597-66vd2mdu 467 2 an an DT cord-014597-66vd2mdu 467 3 elevation elevation NN cord-014597-66vd2mdu 467 4 in in IN cord-014597-66vd2mdu 467 5 titer titer NN cord-014597-66vd2mdu 467 6 up up IN cord-014597-66vd2mdu 467 7 to to TO cord-014597-66vd2mdu 467 8 25 25 CD cord-014597-66vd2mdu 467 9 % % NN cord-014597-66vd2mdu 467 10 in in IN cord-014597-66vd2mdu 467 11 the the DT cord-014597-66vd2mdu 467 12 best good JJS cord-014597-66vd2mdu 467 13 condition condition NN cord-014597-66vd2mdu 467 14 of of IN cord-014597-66vd2mdu 467 15 the the DT cord-014597-66vd2mdu 467 16 cell cell NN cord-014597-66vd2mdu 467 17 lines line NNS cord-014597-66vd2mdu 467 18 clearly clearly RB cord-014597-66vd2mdu 467 19 show show VBP cord-014597-66vd2mdu 467 20 , , , cord-014597-66vd2mdu 467 21 that that IN cord-014597-66vd2mdu 467 22 even even RB cord-014597-66vd2mdu 467 23 state state NN cord-014597-66vd2mdu 467 24 - - HYPH cord-014597-66vd2mdu 467 25 of of IN cord-014597-66vd2mdu 467 26 - - HYPH cord-014597-66vd2mdu 467 27 the the DT cord-014597-66vd2mdu 467 28 - - HYPH cord-014597-66vd2mdu 467 29 art art NN cord-014597-66vd2mdu 467 30 media medium NNS cord-014597-66vd2mdu 467 31 can can MD cord-014597-66vd2mdu 467 32 be be VB cord-014597-66vd2mdu 467 33 outperformed outperform VBN cord-014597-66vd2mdu 467 34 by by IN cord-014597-66vd2mdu 467 35 trace trace NN cord-014597-66vd2mdu 467 36 element element NN cord-014597-66vd2mdu 467 37 rebalancing rebalancing NN cord-014597-66vd2mdu 467 38 . . . cord-014597-66vd2mdu 468 1 Analyzing analyze VBG cord-014597-66vd2mdu 468 2 specific specific JJ cord-014597-66vd2mdu 468 3 rates rate NNS cord-014597-66vd2mdu 468 4 in in IN cord-014597-66vd2mdu 468 5 combination combination NN cord-014597-66vd2mdu 468 6 with with IN cord-014597-66vd2mdu 468 7 metabolic metabolic JJ cord-014597-66vd2mdu 468 8 flux flux NN cord-014597-66vd2mdu 468 9 analysis analysis NN cord-014597-66vd2mdu 468 10 improves improve VBZ cord-014597-66vd2mdu 468 11 the the DT cord-014597-66vd2mdu 468 12 understanding understanding NN cord-014597-66vd2mdu 468 13 of of IN cord-014597-66vd2mdu 468 14 metabolic metabolic JJ cord-014597-66vd2mdu 468 15 restructuring restructuring NN cord-014597-66vd2mdu 468 16 of of IN cord-014597-66vd2mdu 468 17 the the DT cord-014597-66vd2mdu 468 18 cell cell NN cord-014597-66vd2mdu 468 19 lines line NNS cord-014597-66vd2mdu 468 20 under under IN cord-014597-66vd2mdu 468 21 distinct distinct JJ cord-014597-66vd2mdu 468 22 TE TE NNP cord-014597-66vd2mdu 468 23 levels level NNS cord-014597-66vd2mdu 468 24 and and CC cord-014597-66vd2mdu 468 25 combinations combination NNS cord-014597-66vd2mdu 468 26 . . . cord-014597-66vd2mdu 469 1 Modulation modulation NN cord-014597-66vd2mdu 469 2 of of IN cord-014597-66vd2mdu 469 3 trace trace NN cord-014597-66vd2mdu 469 4 elements element NNS cord-014597-66vd2mdu 469 5 levels level NNS cord-014597-66vd2mdu 469 6 had have VBD cord-014597-66vd2mdu 469 7 a a DT cord-014597-66vd2mdu 469 8 tremendous tremendous JJ cord-014597-66vd2mdu 469 9 effect effect NN cord-014597-66vd2mdu 469 10 on on IN cord-014597-66vd2mdu 469 11 the the DT cord-014597-66vd2mdu 469 12 charge charge NN cord-014597-66vd2mdu 469 13 heterogeneity heterogeneity NN cord-014597-66vd2mdu 469 14 and and CC cord-014597-66vd2mdu 469 15 glycosylation glycosylation NN cord-014597-66vd2mdu 469 16 structure structure NN cord-014597-66vd2mdu 469 17 of of IN cord-014597-66vd2mdu 469 18 the the DT cord-014597-66vd2mdu 469 19 different different JJ cord-014597-66vd2mdu 469 20 proteins protein NNS cord-014597-66vd2mdu 469 21 . . . cord-014597-66vd2mdu 470 1 This this DT cord-014597-66vd2mdu 470 2 provides provide VBZ cord-014597-66vd2mdu 470 3 a a DT cord-014597-66vd2mdu 470 4 toolbox toolbox NN cord-014597-66vd2mdu 470 5 for for IN cord-014597-66vd2mdu 470 6 the the DT cord-014597-66vd2mdu 470 7 fine fine JJ cord-014597-66vd2mdu 470 8 tuning tuning NN cord-014597-66vd2mdu 470 9 and and CC cord-014597-66vd2mdu 470 10 control control NN cord-014597-66vd2mdu 470 11 of of IN cord-014597-66vd2mdu 470 12 product product NN cord-014597-66vd2mdu 470 13 quality quality NN cord-014597-66vd2mdu 470 14 parameters parameter NNS cord-014597-66vd2mdu 470 15 . . . cord-014597-66vd2mdu 471 1 Taken take VBN cord-014597-66vd2mdu 471 2 together together RB cord-014597-66vd2mdu 471 3 , , , cord-014597-66vd2mdu 471 4 the the DT cord-014597-66vd2mdu 471 5 data datum NNS cord-014597-66vd2mdu 471 6 further further RB cord-014597-66vd2mdu 471 7 paves pave VBZ cord-014597-66vd2mdu 471 8 the the DT cord-014597-66vd2mdu 471 9 way way NN cord-014597-66vd2mdu 471 10 to to IN cord-014597-66vd2mdu 471 11 the the DT cord-014597-66vd2mdu 471 12 rational rational JJ cord-014597-66vd2mdu 471 13 fine fine JJ cord-014597-66vd2mdu 471 14 tuning tuning NN cord-014597-66vd2mdu 471 15 of of IN cord-014597-66vd2mdu 471 16 process process NN cord-014597-66vd2mdu 471 17 performance performance NN cord-014597-66vd2mdu 471 18 and and CC cord-014597-66vd2mdu 471 19 product product NN cord-014597-66vd2mdu 471 20 quality quality NN cord-014597-66vd2mdu 471 21 attributes attribute NNS cord-014597-66vd2mdu 471 22 . . . cord-014597-66vd2mdu 472 1 Background background NN cord-014597-66vd2mdu 472 2 Due due IN cord-014597-66vd2mdu 472 3 to to IN cord-014597-66vd2mdu 472 4 regulatory regulatory JJ cord-014597-66vd2mdu 472 5 concerns concern NNS cord-014597-66vd2mdu 472 6 and and CC cord-014597-66vd2mdu 472 7 economic economic JJ cord-014597-66vd2mdu 472 8 impact impact NN cord-014597-66vd2mdu 472 9 , , , cord-014597-66vd2mdu 472 10 ensuring ensure VBG cord-014597-66vd2mdu 472 11 product product NN cord-014597-66vd2mdu 472 12 quality quality NN cord-014597-66vd2mdu 472 13 and and CC cord-014597-66vd2mdu 472 14 consistency consistency NN cord-014597-66vd2mdu 472 15 is be VBZ cord-014597-66vd2mdu 472 16 now now RB cord-014597-66vd2mdu 472 17 one one CD cord-014597-66vd2mdu 472 18 of of IN cord-014597-66vd2mdu 472 19 the the DT cord-014597-66vd2mdu 472 20 main main JJ cord-014597-66vd2mdu 472 21 challenge challenge NN cord-014597-66vd2mdu 472 22 faced face VBN cord-014597-66vd2mdu 472 23 by by IN cord-014597-66vd2mdu 472 24 the the DT cord-014597-66vd2mdu 472 25 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 472 26 industry industry NN cord-014597-66vd2mdu 472 27 . . . cord-014597-66vd2mdu 473 1 For for IN cord-014597-66vd2mdu 473 2 monoclonal monoclonal JJ cord-014597-66vd2mdu 473 3 antibodies antibody NNS cord-014597-66vd2mdu 473 4 ( ( -LRB- cord-014597-66vd2mdu 473 5 mAb mAb NNS cord-014597-66vd2mdu 473 6 ) ) -RRB- cord-014597-66vd2mdu 473 7 , , , cord-014597-66vd2mdu 473 8 glycosylation glycosylation NN cord-014597-66vd2mdu 473 9 is be VBZ cord-014597-66vd2mdu 473 10 one one CD cord-014597-66vd2mdu 473 11 of of IN cord-014597-66vd2mdu 473 12 the the DT cord-014597-66vd2mdu 473 13 most most RBS cord-014597-66vd2mdu 473 14 important important JJ cord-014597-66vd2mdu 473 15 quality quality NN cord-014597-66vd2mdu 473 16 attributes attribute NNS cord-014597-66vd2mdu 473 17 as as IN cord-014597-66vd2mdu 473 18 it -PRON- PRP cord-014597-66vd2mdu 473 19 impacts impact VBZ cord-014597-66vd2mdu 473 20 on on IN cord-014597-66vd2mdu 473 21 mAb mab NN cord-014597-66vd2mdu 473 22 structure structure NN cord-014597-66vd2mdu 473 23 integrity integrity NN cord-014597-66vd2mdu 473 24 , , , cord-014597-66vd2mdu 473 25 and and CC cord-014597-66vd2mdu 473 26 ultimately ultimately RB cord-014597-66vd2mdu 473 27 on on IN cord-014597-66vd2mdu 473 28 both both CC cord-014597-66vd2mdu 473 29 clinical clinical JJ cord-014597-66vd2mdu 473 30 efficacy efficacy NN cord-014597-66vd2mdu 473 31 and and CC cord-014597-66vd2mdu 473 32 safety safety NN cord-014597-66vd2mdu 473 33 . . . cord-014597-66vd2mdu 474 1 Many many JJ cord-014597-66vd2mdu 474 2 factors factor NNS cord-014597-66vd2mdu 474 3 affect affect VBP cord-014597-66vd2mdu 474 4 mAb mab NN cord-014597-66vd2mdu 474 5 glycosylation glycosylation NN cord-014597-66vd2mdu 474 6 and and CC cord-014597-66vd2mdu 474 7 its -PRON- PRP$ cord-014597-66vd2mdu 474 8 inherent inherent JJ cord-014597-66vd2mdu 474 9 heterogeneity heterogeneity NN cord-014597-66vd2mdu 474 10 , , , cord-014597-66vd2mdu 474 11 including include VBG cord-014597-66vd2mdu 474 12 the the DT cord-014597-66vd2mdu 474 13 host host NN cord-014597-66vd2mdu 474 14 cell cell NN cord-014597-66vd2mdu 474 15 , , , cord-014597-66vd2mdu 474 16 the the DT cord-014597-66vd2mdu 474 17 culture culture NN cord-014597-66vd2mdu 474 18 medium medium NN cord-014597-66vd2mdu 474 19 , , , cord-014597-66vd2mdu 474 20 the the DT cord-014597-66vd2mdu 474 21 mode mode NN cord-014597-66vd2mdu 474 22 of of IN cord-014597-66vd2mdu 474 23 operation operation NN cord-014597-66vd2mdu 474 24 and and CC cord-014597-66vd2mdu 474 25 the the DT cord-014597-66vd2mdu 474 26 operating operating NN cord-014597-66vd2mdu 474 27 conditions condition NNS cord-014597-66vd2mdu 474 28 . . . cord-014597-66vd2mdu 475 1 In in IN cord-014597-66vd2mdu 475 2 this this DT cord-014597-66vd2mdu 475 3 context context NN cord-014597-66vd2mdu 475 4 , , , cord-014597-66vd2mdu 475 5 the the DT cord-014597-66vd2mdu 475 6 capacity capacity NN cord-014597-66vd2mdu 475 7 to to TO cord-014597-66vd2mdu 475 8 monitor monitor VB cord-014597-66vd2mdu 475 9 and and CC cord-014597-66vd2mdu 475 10 control control VB cord-014597-66vd2mdu 475 11 on on IN cord-014597-66vd2mdu 475 12 - - HYPH cord-014597-66vd2mdu 475 13 line line NN cord-014597-66vd2mdu 475 14 the the DT cord-014597-66vd2mdu 475 15 antibody antibody NN cord-014597-66vd2mdu 475 16 glycosylation glycosylation NN cord-014597-66vd2mdu 475 17 , , , cord-014597-66vd2mdu 475 18 from from IN cord-014597-66vd2mdu 475 19 early early JJ cord-014597-66vd2mdu 475 20 - - HYPH cord-014597-66vd2mdu 475 21 to to IN cord-014597-66vd2mdu 475 22 late late JJ cord-014597-66vd2mdu 475 23 - - HYPH cord-014597-66vd2mdu 475 24 stage stage NN cord-014597-66vd2mdu 475 25 process process NN cord-014597-66vd2mdu 475 26 development development NN cord-014597-66vd2mdu 475 27 , , , cord-014597-66vd2mdu 475 28 would would MD cord-014597-66vd2mdu 475 29 be be VB cord-014597-66vd2mdu 475 30 of of IN cord-014597-66vd2mdu 475 31 salient salient JJ cord-014597-66vd2mdu 475 32 interest interest NN cord-014597-66vd2mdu 475 33 to to TO cord-014597-66vd2mdu 475 34 reduce reduce VB cord-014597-66vd2mdu 475 35 the the DT cord-014597-66vd2mdu 475 36 time time NN cord-014597-66vd2mdu 475 37 and and CC cord-014597-66vd2mdu 475 38 cost cost VBD cord-014597-66vd2mdu 475 39 to to IN cord-014597-66vd2mdu 475 40 market market NN cord-014597-66vd2mdu 475 41 . . . cord-014597-66vd2mdu 476 1 In in IN cord-014597-66vd2mdu 476 2 order order NN cord-014597-66vd2mdu 476 3 to to TO cord-014597-66vd2mdu 476 4 address address VB cord-014597-66vd2mdu 476 5 this this DT cord-014597-66vd2mdu 476 6 unmet unmet JJ cord-014597-66vd2mdu 476 7 need need NN cord-014597-66vd2mdu 476 8 , , , cord-014597-66vd2mdu 476 9 we -PRON- PRP cord-014597-66vd2mdu 476 10 have have VBP cord-014597-66vd2mdu 476 11 designed design VBN cord-014597-66vd2mdu 476 12 an an DT cord-014597-66vd2mdu 476 13 improved improve VBN cord-014597-66vd2mdu 476 14 SPR SPR NNP cord-014597-66vd2mdu 476 15 biosensor biosensor NN cord-014597-66vd2mdu 476 16 assay assay NN cord-014597-66vd2mdu 476 17 to to TO cord-014597-66vd2mdu 476 18 measure measure VB cord-014597-66vd2mdu 476 19 the the DT cord-014597-66vd2mdu 476 20 kinetics kinetic NNS cord-014597-66vd2mdu 476 21 of of IN cord-014597-66vd2mdu 476 22 interaction interaction NN cord-014597-66vd2mdu 476 23 between between IN cord-014597-66vd2mdu 476 24 a a DT cord-014597-66vd2mdu 476 25 mAb mAb NNS cord-014597-66vd2mdu 476 26 and and CC cord-014597-66vd2mdu 476 27 the the DT cord-014597-66vd2mdu 476 28 extracellular extracellular JJ cord-014597-66vd2mdu 476 29 domain domain NN cord-014597-66vd2mdu 476 30 of of IN cord-014597-66vd2mdu 476 31 the the DT cord-014597-66vd2mdu 476 32 FcγRIIIa FcγRIIIa NNP cord-014597-66vd2mdu 476 33 receptor receptor NN cord-014597-66vd2mdu 476 34 bound bind VBN cord-014597-66vd2mdu 476 35 at at IN cord-014597-66vd2mdu 476 36 the the DT cord-014597-66vd2mdu 476 37 biosensor biosensor NN cord-014597-66vd2mdu 476 38 surface surface NN cord-014597-66vd2mdu 476 39 [ [ -LRB- cord-014597-66vd2mdu 476 40 1 1 CD cord-014597-66vd2mdu 476 41 , , , cord-014597-66vd2mdu 476 42 2 2 CD cord-014597-66vd2mdu 476 43 ] ] -RRB- cord-014597-66vd2mdu 476 44 . . . cord-014597-66vd2mdu 477 1 Of of IN cord-014597-66vd2mdu 477 2 salient salient JJ cord-014597-66vd2mdu 477 3 interest interest NN cord-014597-66vd2mdu 477 4 , , , cord-014597-66vd2mdu 477 5 we -PRON- PRP cord-014597-66vd2mdu 477 6 also also RB cord-014597-66vd2mdu 477 7 demonstrated demonstrate VBD cord-014597-66vd2mdu 477 8 that that IN cord-014597-66vd2mdu 477 9 various various JJ cord-014597-66vd2mdu 477 10 binding bind VBG cord-014597-66vd2mdu 477 11 kinetic kinetic JJ cord-014597-66vd2mdu 477 12 signatures signature NNS cord-014597-66vd2mdu 477 13 , , , cord-014597-66vd2mdu 477 14 especially especially RB cord-014597-66vd2mdu 477 15 different different JJ cord-014597-66vd2mdu 477 16 dissociation dissociation NN cord-014597-66vd2mdu 477 17 kinetics kinetics NN cord-014597-66vd2mdu 477 18 could could MD cord-014597-66vd2mdu 477 19 be be VB cord-014597-66vd2mdu 477 20 correlated correlate VBN cord-014597-66vd2mdu 477 21 with with IN cord-014597-66vd2mdu 477 22 distinct distinct JJ cord-014597-66vd2mdu 477 23 mAb mAb HYPH cord-014597-66vd2mdu 477 24 glycosylation glycosylation NN cord-014597-66vd2mdu 477 25 patterns pattern NNS cord-014597-66vd2mdu 477 26 and and CC cord-014597-66vd2mdu 477 27 with with IN cord-014597-66vd2mdu 477 28 therapeutic therapeutic JJ cord-014597-66vd2mdu 477 29 efficacies efficacy NNS cord-014597-66vd2mdu 477 30 , , , cord-014597-66vd2mdu 477 31 as as IN cord-014597-66vd2mdu 477 32 deduced deduce VBN cord-014597-66vd2mdu 477 33 from from IN cord-014597-66vd2mdu 477 34 mass mass NN cord-014597-66vd2mdu 477 35 spectrometry spectrometry NN cord-014597-66vd2mdu 477 36 and and CC cord-014597-66vd2mdu 477 37 a a DT cord-014597-66vd2mdu 477 38 surrogate surrogate JJ cord-014597-66vd2mdu 477 39 ADCC ADCC NNP cord-014597-66vd2mdu 477 40 assay assay NN cord-014597-66vd2mdu 477 41 , , , cord-014597-66vd2mdu 477 42 respectively respectively RB cord-014597-66vd2mdu 477 43 . . . cord-014597-66vd2mdu 478 1 In in IN cord-014597-66vd2mdu 478 2 parallel parallel NN cord-014597-66vd2mdu 478 3 , , , cord-014597-66vd2mdu 478 4 we -PRON- PRP cord-014597-66vd2mdu 478 5 have have VBP cord-014597-66vd2mdu 478 6 also also RB cord-014597-66vd2mdu 478 7 harnessed harness VBN cord-014597-66vd2mdu 478 8 a a DT cord-014597-66vd2mdu 478 9 SPR SPR NNP cord-014597-66vd2mdu 478 10 biosensor biosensor NN cord-014597-66vd2mdu 478 11 directly directly RB cord-014597-66vd2mdu 478 12 to to IN cord-014597-66vd2mdu 478 13 a a DT cord-014597-66vd2mdu 478 14 bioreactor bioreactor NN cord-014597-66vd2mdu 478 15 , , , cord-014597-66vd2mdu 478 16 which which WDT cord-014597-66vd2mdu 478 17 permitted permit VBD cord-014597-66vd2mdu 478 18 the the DT cord-014597-66vd2mdu 478 19 at at IN cord-014597-66vd2mdu 478 20 - - HYPH cord-014597-66vd2mdu 478 21 line line NN cord-014597-66vd2mdu 478 22 determination determination NN cord-014597-66vd2mdu 478 23 of of IN cord-014597-66vd2mdu 478 24 the the DT cord-014597-66vd2mdu 478 25 concentration concentration NN cord-014597-66vd2mdu 478 26 of of IN cord-014597-66vd2mdu 478 27 antibodies antibody NNS cord-014597-66vd2mdu 478 28 by by IN cord-014597-66vd2mdu 478 29 hybridoma hybridoma NN cord-014597-66vd2mdu 478 30 cells cell NNS cord-014597-66vd2mdu 478 31 during during IN cord-014597-66vd2mdu 478 32 a a DT cord-014597-66vd2mdu 478 33 bioreactor bioreactor NN cord-014597-66vd2mdu 478 34 culture culture NN cord-014597-66vd2mdu 478 35 . . . cord-014597-66vd2mdu 479 1 We -PRON- PRP cord-014597-66vd2mdu 479 2 now now RB cord-014597-66vd2mdu 479 3 plan plan VBP cord-014597-66vd2mdu 479 4 on on IN cord-014597-66vd2mdu 479 5 combining combine VBG cord-014597-66vd2mdu 479 6 both both DT cord-014597-66vd2mdu 479 7 approaches approach NNS cord-014597-66vd2mdu 479 8 to to TO cord-014597-66vd2mdu 479 9 determine determine VB cord-014597-66vd2mdu 479 10 on on IN cord-014597-66vd2mdu 479 11 - - HYPH cord-014597-66vd2mdu 479 12 line line NN cord-014597-66vd2mdu 479 13 the the DT cord-014597-66vd2mdu 479 14 glycosylation glycosylation NN cord-014597-66vd2mdu 479 15 profile profile NN cord-014597-66vd2mdu 479 16 of of IN cord-014597-66vd2mdu 479 17 the the DT cord-014597-66vd2mdu 479 18 produced produce VBN cord-014597-66vd2mdu 479 19 mAbs mabs NN cord-014597-66vd2mdu 479 20 . . . cord-014597-66vd2mdu 480 1 Our -PRON- PRP$ cord-014597-66vd2mdu 480 2 ultimate ultimate JJ cord-014597-66vd2mdu 480 3 goal goal NN cord-014597-66vd2mdu 480 4 is be VBZ cord-014597-66vd2mdu 480 5 to to TO cord-014597-66vd2mdu 480 6 design design VB cord-014597-66vd2mdu 480 7 a a DT cord-014597-66vd2mdu 480 8 unique unique JJ cord-014597-66vd2mdu 480 9 and and CC cord-014597-66vd2mdu 480 10 highly highly RB cord-014597-66vd2mdu 480 11 innovative innovative JJ cord-014597-66vd2mdu 480 12 bioprocess bioprocess NN cord-014597-66vd2mdu 480 13 control control NN cord-014597-66vd2mdu 480 14 tool tool NN cord-014597-66vd2mdu 480 15 that that WDT cord-014597-66vd2mdu 480 16 can can MD cord-014597-66vd2mdu 480 17 be be VB cord-014597-66vd2mdu 480 18 readily readily RB cord-014597-66vd2mdu 480 19 applied apply VBN cord-014597-66vd2mdu 480 20 in in IN cord-014597-66vd2mdu 480 21 an an DT cord-014597-66vd2mdu 480 22 industrial industrial JJ cord-014597-66vd2mdu 480 23 bio bio NN cord-014597-66vd2mdu 480 24 - - HYPH cord-014597-66vd2mdu 480 25 manufacturing manufacturing NN cord-014597-66vd2mdu 480 26 setting setting NN cord-014597-66vd2mdu 480 27 . . . cord-014597-66vd2mdu 481 1 Reducing reduce VBG cord-014597-66vd2mdu 481 2 timelines timeline NNS cord-014597-66vd2mdu 481 3 and and CC cord-014597-66vd2mdu 481 4 costs cost NNS cord-014597-66vd2mdu 481 5 are be VBP cord-014597-66vd2mdu 481 6 key key JJ cord-014597-66vd2mdu 481 7 factors factor NNS cord-014597-66vd2mdu 481 8 for for IN cord-014597-66vd2mdu 481 9 bio bio JJ cord-014597-66vd2mdu 481 10 - - JJ cord-014597-66vd2mdu 481 11 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 481 12 industries industry NNS cord-014597-66vd2mdu 481 13 to to TO cord-014597-66vd2mdu 481 14 accelerate accelerate VB cord-014597-66vd2mdu 481 15 process process NN cord-014597-66vd2mdu 481 16 development development NN cord-014597-66vd2mdu 481 17 and and CC cord-014597-66vd2mdu 481 18 drug drug NN cord-014597-66vd2mdu 481 19 delivery delivery NN cord-014597-66vd2mdu 481 20 to to IN cord-014597-66vd2mdu 481 21 patients patient NNS cord-014597-66vd2mdu 481 22 . . . cord-014597-66vd2mdu 482 1 Enhancing enhance VBG cord-014597-66vd2mdu 482 2 throughput throughput NN cord-014597-66vd2mdu 482 3 of of IN cord-014597-66vd2mdu 482 4 bioprocess bioprocess NN cord-014597-66vd2mdu 482 5 development development NN cord-014597-66vd2mdu 482 6 has have VBZ cord-014597-66vd2mdu 482 7 become become VBN cord-014597-66vd2mdu 482 8 increasingly increasingly RB cord-014597-66vd2mdu 482 9 important important JJ cord-014597-66vd2mdu 482 10 for for IN cord-014597-66vd2mdu 482 11 the the DT cord-014597-66vd2mdu 482 12 screening screening NN cord-014597-66vd2mdu 482 13 and and CC cord-014597-66vd2mdu 482 14 optimization optimization NN cord-014597-66vd2mdu 482 15 of of IN cord-014597-66vd2mdu 482 16 cell cell NN cord-014597-66vd2mdu 482 17 culture culture NN cord-014597-66vd2mdu 482 18 processes process NNS cord-014597-66vd2mdu 482 19 . . . cord-014597-66vd2mdu 483 1 This this DT cord-014597-66vd2mdu 483 2 challenge challenge NN cord-014597-66vd2mdu 483 3 requires require VBZ cord-014597-66vd2mdu 483 4 high high JJ cord-014597-66vd2mdu 483 5 throughput throughput NN cord-014597-66vd2mdu 483 6 tools tool NNS cord-014597-66vd2mdu 483 7 . . . cord-014597-66vd2mdu 484 1 In in IN cord-014597-66vd2mdu 484 2 a a DT cord-014597-66vd2mdu 484 3 previous previous JJ cord-014597-66vd2mdu 484 4 study study NN cord-014597-66vd2mdu 484 5 [ [ -LRB- cord-014597-66vd2mdu 484 6 1 1 CD cord-014597-66vd2mdu 484 7 ] ] -RRB- cord-014597-66vd2mdu 484 8 , , , cord-014597-66vd2mdu 484 9 we -PRON- PRP cord-014597-66vd2mdu 484 10 showed show VBD cord-014597-66vd2mdu 484 11 that that IN cord-014597-66vd2mdu 484 12 ambr ambr NNP cord-014597-66vd2mdu 484 13 ® ® NNP cord-014597-66vd2mdu 484 14 15 15 CD cord-014597-66vd2mdu 484 15 , , , cord-014597-66vd2mdu 484 16 a a DT cord-014597-66vd2mdu 484 17 robotically robotically RB cord-014597-66vd2mdu 484 18 driven drive VBN cord-014597-66vd2mdu 484 19 mini mini NN cord-014597-66vd2mdu 484 20 - - NN cord-014597-66vd2mdu 484 21 bioreactor bioreactor NN cord-014597-66vd2mdu 484 22 system system NN cord-014597-66vd2mdu 484 23 developed develop VBN cord-014597-66vd2mdu 484 24 by by IN cord-014597-66vd2mdu 484 25 TAP TAP NNP cord-014597-66vd2mdu 484 26 - - HYPH cord-014597-66vd2mdu 484 27 Sartorius Sartorius NNP cord-014597-66vd2mdu 484 28 , , , cord-014597-66vd2mdu 484 29 could could MD cord-014597-66vd2mdu 484 30 be be VB cord-014597-66vd2mdu 484 31 advantageous advantageous JJ cord-014597-66vd2mdu 484 32 to to TO cord-014597-66vd2mdu 484 33 accelerate accelerate VB cord-014597-66vd2mdu 484 34 process process NN cord-014597-66vd2mdu 484 35 development development NN cord-014597-66vd2mdu 484 36 . . . cord-014597-66vd2mdu 485 1 The the DT cord-014597-66vd2mdu 485 2 use use NN cord-014597-66vd2mdu 485 3 of of IN cord-014597-66vd2mdu 485 4 ambr ambr NNP cord-014597-66vd2mdu 485 5 ® ® NNP cord-014597-66vd2mdu 485 6 15 15 CD cord-014597-66vd2mdu 485 7 system system NN cord-014597-66vd2mdu 485 8 allows allow VBZ cord-014597-66vd2mdu 485 9 us -PRON- PRP cord-014597-66vd2mdu 485 10 to to TO cord-014597-66vd2mdu 485 11 test test VB cord-014597-66vd2mdu 485 12 a a DT cord-014597-66vd2mdu 485 13 large large JJ cord-014597-66vd2mdu 485 14 number number NN cord-014597-66vd2mdu 485 15 of of IN cord-014597-66vd2mdu 485 16 experimental experimental JJ cord-014597-66vd2mdu 485 17 conditions condition NNS cord-014597-66vd2mdu 485 18 in in IN cord-014597-66vd2mdu 485 19 a a DT cord-014597-66vd2mdu 485 20 single single JJ cord-014597-66vd2mdu 485 21 experiment experiment NN cord-014597-66vd2mdu 485 22 . . . cord-014597-66vd2mdu 486 1 Therefore therefore RB cord-014597-66vd2mdu 486 2 , , , cord-014597-66vd2mdu 486 3 the the DT cord-014597-66vd2mdu 486 4 large large JJ cord-014597-66vd2mdu 486 5 amount amount NN cord-014597-66vd2mdu 486 6 of of IN cord-014597-66vd2mdu 486 7 production production NN cord-014597-66vd2mdu 486 8 samples sample NNS cord-014597-66vd2mdu 486 9 to to TO cord-014597-66vd2mdu 486 10 be be VB cord-014597-66vd2mdu 486 11 characterized characterize VBN cord-014597-66vd2mdu 486 12 for for IN cord-014597-66vd2mdu 486 13 Product product NN cord-014597-66vd2mdu 486 14 Quality quality NN cord-014597-66vd2mdu 486 15 Attributes Attributes NNPS cord-014597-66vd2mdu 486 16 ( ( -LRB- cord-014597-66vd2mdu 486 17 PQA PQA NNP cord-014597-66vd2mdu 486 18 ) ) -RRB- cord-014597-66vd2mdu 486 19 increases increase VBZ cord-014597-66vd2mdu 486 20 as as RB cord-014597-66vd2mdu 486 21 well well RB cord-014597-66vd2mdu 486 22 : : : cord-014597-66vd2mdu 486 23 the the DT cord-014597-66vd2mdu 486 24 bottleneck bottleneck NN cord-014597-66vd2mdu 486 25 has have VBZ cord-014597-66vd2mdu 486 26 moved move VBN cord-014597-66vd2mdu 486 27 from from IN cord-014597-66vd2mdu 486 28 the the DT cord-014597-66vd2mdu 486 29 generation generation NN cord-014597-66vd2mdu 486 30 of of IN cord-014597-66vd2mdu 486 31 samples sample NNS cord-014597-66vd2mdu 486 32 at at IN cord-014597-66vd2mdu 486 33 the the DT cord-014597-66vd2mdu 486 34 production production NN cord-014597-66vd2mdu 486 35 bioreactor bioreactor NN cord-014597-66vd2mdu 486 36 step step NN cord-014597-66vd2mdu 486 37 to to IN cord-014597-66vd2mdu 486 38 in in IN cord-014597-66vd2mdu 486 39 - - HYPH cord-014597-66vd2mdu 486 40 process process NN cord-014597-66vd2mdu 486 41 analysis analysis NN cord-014597-66vd2mdu 486 42 . . . cord-014597-66vd2mdu 487 1 For for IN cord-014597-66vd2mdu 487 2 product product NN cord-014597-66vd2mdu 487 3 quality quality NN cord-014597-66vd2mdu 487 4 attribute attribute NN cord-014597-66vd2mdu 487 5 analysis analysis NN cord-014597-66vd2mdu 487 6 at at IN cord-014597-66vd2mdu 487 7 lab lab NN cord-014597-66vd2mdu 487 8 scale scale NN cord-014597-66vd2mdu 487 9 , , , cord-014597-66vd2mdu 487 10 protein protein NN cord-014597-66vd2mdu 487 11 purification purification NN cord-014597-66vd2mdu 487 12 is be VBZ cord-014597-66vd2mdu 487 13 generally generally RB cord-014597-66vd2mdu 487 14 carried carry VBN cord-014597-66vd2mdu 487 15 out out RP cord-014597-66vd2mdu 487 16 on on IN cord-014597-66vd2mdu 487 17 > > $ cord-014597-66vd2mdu 487 18 5mL 5ml CD cord-014597-66vd2mdu 487 19 columns column NNS cord-014597-66vd2mdu 487 20 which which WDT cord-014597-66vd2mdu 487 21 is be VBZ cord-014597-66vd2mdu 487 22 incompatible incompatible JJ cord-014597-66vd2mdu 487 23 with with IN cord-014597-66vd2mdu 487 24 the the DT cord-014597-66vd2mdu 487 25 size size NN cord-014597-66vd2mdu 487 26 of of IN cord-014597-66vd2mdu 487 27 ambr ambr NNP cord-014597-66vd2mdu 487 28 ® ® NNP cord-014597-66vd2mdu 487 29 15 15 CD cord-014597-66vd2mdu 487 30 bioreactors bioreactor NNS cord-014597-66vd2mdu 487 31 . . . cord-014597-66vd2mdu 488 1 Moreover moreover RB cord-014597-66vd2mdu 488 2 , , , cord-014597-66vd2mdu 488 3 the the DT cord-014597-66vd2mdu 488 4 applied apply VBN cord-014597-66vd2mdu 488 5 methods method NNS cord-014597-66vd2mdu 488 6 are be VBP cord-014597-66vd2mdu 488 7 relatively relatively RB cord-014597-66vd2mdu 488 8 low low JJ cord-014597-66vd2mdu 488 9 throughput throughput NN cord-014597-66vd2mdu 488 10 . . . cord-014597-66vd2mdu 489 1 The the DT cord-014597-66vd2mdu 489 2 development development NN cord-014597-66vd2mdu 489 3 of of IN cord-014597-66vd2mdu 489 4 a a DT cord-014597-66vd2mdu 489 5 high high JJ cord-014597-66vd2mdu 489 6 binding binding NN cord-014597-66vd2mdu 489 7 capacity capacity NN cord-014597-66vd2mdu 489 8 resin resin NN cord-014597-66vd2mdu 489 9 ( ( -LRB- cord-014597-66vd2mdu 489 10 up up IN cord-014597-66vd2mdu 489 11 to to TO cord-014597-66vd2mdu 489 12 70 70 CD cord-014597-66vd2mdu 489 13 mg mg NN cord-014597-66vd2mdu 489 14 / / SYM cord-014597-66vd2mdu 489 15 mL ml NN cord-014597-66vd2mdu 489 16 ) ) -RRB- cord-014597-66vd2mdu 489 17 [ [ -LRB- cord-014597-66vd2mdu 489 18 2 2 CD cord-014597-66vd2mdu 489 19 ] ] -RRB- cord-014597-66vd2mdu 489 20 , , , cord-014597-66vd2mdu 489 21 combined combine VBN cord-014597-66vd2mdu 489 22 with with IN cord-014597-66vd2mdu 489 23 high high JJ cord-014597-66vd2mdu 489 24 performing perform VBG cord-014597-66vd2mdu 489 25 new new JJ cord-014597-66vd2mdu 489 26 cell cell NN cord-014597-66vd2mdu 489 27 lines line NNS cord-014597-66vd2mdu 489 28 which which WDT cord-014597-66vd2mdu 489 29 are be VBP cord-014597-66vd2mdu 489 30 able able JJ cord-014597-66vd2mdu 489 31 to to TO cord-014597-66vd2mdu 489 32 produce produce VB cord-014597-66vd2mdu 489 33 up up RP cord-014597-66vd2mdu 489 34 to to TO cord-014597-66vd2mdu 489 35 5 5 CD cord-014597-66vd2mdu 489 36 g g NN cord-014597-66vd2mdu 489 37 / / SYM cord-014597-66vd2mdu 489 38 L l NN cord-014597-66vd2mdu 489 39 of of IN cord-014597-66vd2mdu 489 40 recombinant recombinant JJ cord-014597-66vd2mdu 489 41 monoclonal monoclonal JJ cord-014597-66vd2mdu 489 42 antibodies antibody NNS cord-014597-66vd2mdu 489 43 , , , cord-014597-66vd2mdu 489 44 allow allow VBP cord-014597-66vd2mdu 489 45 require require VB cord-014597-66vd2mdu 489 46 the the DT cord-014597-66vd2mdu 489 47 development development NN cord-014597-66vd2mdu 489 48 of of IN cord-014597-66vd2mdu 489 49 an an DT cord-014597-66vd2mdu 489 50 efficient efficient JJ cord-014597-66vd2mdu 489 51 and and CC cord-014597-66vd2mdu 489 52 high high JJ cord-014597-66vd2mdu 489 53 throughput throughput NN cord-014597-66vd2mdu 489 54 ( ( -LRB- cord-014597-66vd2mdu 489 55 HTS HTS NNP cord-014597-66vd2mdu 489 56 ) ) -RRB- cord-014597-66vd2mdu 489 57 purification purification NN cord-014597-66vd2mdu 489 58 method method NN cord-014597-66vd2mdu 489 59 robot robot NN cord-014597-66vd2mdu 489 60 . . . cord-014597-66vd2mdu 490 1 The the DT cord-014597-66vd2mdu 490 2 use use NN cord-014597-66vd2mdu 490 3 of of IN cord-014597-66vd2mdu 490 4 robotic robotic JJ cord-014597-66vd2mdu 490 5 equipment equipment NN cord-014597-66vd2mdu 490 6 for for IN cord-014597-66vd2mdu 490 7 small small JJ cord-014597-66vd2mdu 490 8 scale scale NN cord-014597-66vd2mdu 490 9 purification purification NN cord-014597-66vd2mdu 490 10 purposes purpose NNS cord-014597-66vd2mdu 490 11 is be VBZ cord-014597-66vd2mdu 490 12 a a DT cord-014597-66vd2mdu 490 13 great great JJ cord-014597-66vd2mdu 490 14 opportunity opportunity NN cord-014597-66vd2mdu 490 15 for for IN cord-014597-66vd2mdu 490 16 us -PRON- PRP cord-014597-66vd2mdu 490 17 to to TO cord-014597-66vd2mdu 490 18 tackle tackle VB cord-014597-66vd2mdu 490 19 this this DT cord-014597-66vd2mdu 490 20 bottleneck bottleneck NN cord-014597-66vd2mdu 490 21 , , , cord-014597-66vd2mdu 490 22 by by IN cord-014597-66vd2mdu 490 23 enabling enable VBG cord-014597-66vd2mdu 490 24 highthroughput highthroughput NN cord-014597-66vd2mdu 490 25 sample sample NN cord-014597-66vd2mdu 490 26 purification purification NN cord-014597-66vd2mdu 490 27 at at IN cord-014597-66vd2mdu 490 28 smaller small JJR cord-014597-66vd2mdu 490 29 scale scale NN cord-014597-66vd2mdu 490 30 ( ( -LRB- cord-014597-66vd2mdu 490 31 200μL 200μl CD cord-014597-66vd2mdu 490 32 ) ) -RRB- cord-014597-66vd2mdu 490 33 . . . cord-014597-66vd2mdu 491 1 Recombinant recombinant JJ cord-014597-66vd2mdu 491 2 monoclonal monoclonal JJ cord-014597-66vd2mdu 491 3 antibodies antibody NNS cord-014597-66vd2mdu 491 4 were be VBD cord-014597-66vd2mdu 491 5 produced produce VBN cord-014597-66vd2mdu 491 6 by by IN cord-014597-66vd2mdu 491 7 a a DT cord-014597-66vd2mdu 491 8 genetically genetically RB cord-014597-66vd2mdu 491 9 engineered engineer VBN cord-014597-66vd2mdu 491 10 Dihydrofolate Dihydrofolate NNP cord-014597-66vd2mdu 491 11 Reductase Reductase NNP cord-014597-66vd2mdu 491 12 ( ( -LRB- cord-014597-66vd2mdu 491 13 DHFR)-/-DG44 dhfr)-/-dg44 JJ cord-014597-66vd2mdu 491 14 Chinese chinese JJ cord-014597-66vd2mdu 491 15 Hamster Hamster NNP cord-014597-66vd2mdu 491 16 Ovary Ovary NNP cord-014597-66vd2mdu 491 17 ( ( -LRB- cord-014597-66vd2mdu 491 18 CHO CHO NNP cord-014597-66vd2mdu 491 19 ) ) -RRB- cord-014597-66vd2mdu 491 20 cell cell NN cord-014597-66vd2mdu 491 21 line line NN cord-014597-66vd2mdu 491 22 . . . cord-014597-66vd2mdu 492 1 Clarified clarify VBN cord-014597-66vd2mdu 492 2 cell cell NN cord-014597-66vd2mdu 492 3 culture culture NN cord-014597-66vd2mdu 492 4 fluid fluid NN cord-014597-66vd2mdu 492 5 ( ( -LRB- cord-014597-66vd2mdu 492 6 CCCF CCCF NNP cord-014597-66vd2mdu 492 7 ) ) -RRB- cord-014597-66vd2mdu 492 8 was be VBD cord-014597-66vd2mdu 492 9 obtained obtain VBN cord-014597-66vd2mdu 492 10 from from IN cord-014597-66vd2mdu 492 11 2 2 CD cord-014597-66vd2mdu 492 12 and and CC cord-014597-66vd2mdu 492 13 2 2 CD cord-014597-66vd2mdu 492 14 K k NN cord-014597-66vd2mdu 492 15 liter liter NN cord-014597-66vd2mdu 492 16 bioreactors bioreactor NNS cord-014597-66vd2mdu 492 17 after after IN cord-014597-66vd2mdu 492 18 three three CD cord-014597-66vd2mdu 492 19 filtration filtration NN cord-014597-66vd2mdu 492 20 steps step NNS cord-014597-66vd2mdu 492 21 . . . cord-014597-66vd2mdu 493 1 Minipurifications minipurification NNS cord-014597-66vd2mdu 493 2 were be VBD cord-014597-66vd2mdu 493 3 performed perform VBN cord-014597-66vd2mdu 493 4 on on IN cord-014597-66vd2mdu 494 1 Tecan Tecan NNP cord-014597-66vd2mdu 494 2 Freedom Freedom NNP cord-014597-66vd2mdu 494 3 EVO EVO NNP cord-014597-66vd2mdu 494 4 ® ® NN cord-014597-66vd2mdu 494 5 robot robot NN cord-014597-66vd2mdu 494 6 with with IN cord-014597-66vd2mdu 494 7 PreDictor PreDictor NNP cord-014597-66vd2mdu 494 8 RoboCol RoboCol NNP cord-014597-66vd2mdu 494 9 - - HYPH cord-014597-66vd2mdu 494 10 umns umns NNP cord-014597-66vd2mdu 495 1 ® ® LS cord-014597-66vd2mdu 495 2 containing contain VBG cord-014597-66vd2mdu 495 3 200μL 200μl CD cord-014597-66vd2mdu 495 4 Mabselect Mabselect NNP cord-014597-66vd2mdu 495 5 SuRe SuRe NNP cord-014597-66vd2mdu 495 6 ® ® POS cord-014597-66vd2mdu 495 7 resin resin NN cord-014597-66vd2mdu 495 8 . . . cord-014597-66vd2mdu 496 1 Larger large JJR cord-014597-66vd2mdu 496 2 scale scale NN cord-014597-66vd2mdu 496 3 purification purification NN cord-014597-66vd2mdu 496 4 were be VBD cord-014597-66vd2mdu 496 5 executed execute VBN cord-014597-66vd2mdu 496 6 using use VBG cord-014597-66vd2mdu 496 7 an an DT cord-014597-66vd2mdu 496 8 AktaXpress AktaXpress NNP cord-014597-66vd2mdu 496 9 using use VBG cord-014597-66vd2mdu 496 10 Hitrap Hitrap NNP cord-014597-66vd2mdu 496 11 column column NN cord-014597-66vd2mdu 496 12 ProtA. ProtA. NNS cord-014597-66vd2mdu 496 13 To to TO cord-014597-66vd2mdu 496 14 assess assess VB cord-014597-66vd2mdu 496 15 monoclonal monoclonal JJ cord-014597-66vd2mdu 496 16 antibody antibody NN cord-014597-66vd2mdu 496 17 purification purification NN cord-014597-66vd2mdu 496 18 at at IN cord-014597-66vd2mdu 496 19 small small JJ cord-014597-66vd2mdu 496 20 scale scale NN cord-014597-66vd2mdu 496 21 , , , cord-014597-66vd2mdu 496 22 we -PRON- PRP cord-014597-66vd2mdu 496 23 first first RB cord-014597-66vd2mdu 496 24 tested test VBD cord-014597-66vd2mdu 496 25 the the DT cord-014597-66vd2mdu 496 26 repeatability repeatability NN cord-014597-66vd2mdu 496 27 of of IN cord-014597-66vd2mdu 496 28 the the DT cord-014597-66vd2mdu 496 29 minipurification minipurification NN cord-014597-66vd2mdu 496 30 , , , cord-014597-66vd2mdu 496 31 purifying purify VBG cord-014597-66vd2mdu 496 32 the the DT cord-014597-66vd2mdu 496 33 samples sample NNS cord-014597-66vd2mdu 496 34 8 8 CD cord-014597-66vd2mdu 496 35 times time NNS cord-014597-66vd2mdu 496 36 on on IN cord-014597-66vd2mdu 496 37 the the DT cord-014597-66vd2mdu 496 38 same same JJ cord-014597-66vd2mdu 496 39 columns column NNS cord-014597-66vd2mdu 496 40 and and CC cord-014597-66vd2mdu 496 41 using use VBG cord-014597-66vd2mdu 496 42 different different JJ cord-014597-66vd2mdu 496 43 columns column NNS cord-014597-66vd2mdu 496 44 , , , cord-014597-66vd2mdu 496 45 focusing focus VBG cord-014597-66vd2mdu 496 46 on on IN cord-014597-66vd2mdu 496 47 the the DT cord-014597-66vd2mdu 496 48 yield yield NN cord-014597-66vd2mdu 496 49 of of IN cord-014597-66vd2mdu 496 50 the the DT cord-014597-66vd2mdu 496 51 purification purification NN cord-014597-66vd2mdu 496 52 and and CC cord-014597-66vd2mdu 496 53 the the DT cord-014597-66vd2mdu 496 54 impact impact NN cord-014597-66vd2mdu 496 55 on on IN cord-014597-66vd2mdu 496 56 Product Product NNP cord-014597-66vd2mdu 496 57 Quality Quality NNP cord-014597-66vd2mdu 496 58 Attributes Attributes NNPS cord-014597-66vd2mdu 496 59 , , , cord-014597-66vd2mdu 496 60 especially especially RB cord-014597-66vd2mdu 496 61 the the DT cord-014597-66vd2mdu 496 62 HMWS HMWS NNP cord-014597-66vd2mdu 496 63 . . . cord-014597-66vd2mdu 497 1 Then then RB cord-014597-66vd2mdu 497 2 , , , cord-014597-66vd2mdu 497 3 we -PRON- PRP cord-014597-66vd2mdu 497 4 compared compare VBD cord-014597-66vd2mdu 497 5 those those DT cord-014597-66vd2mdu 497 6 results result NNS cord-014597-66vd2mdu 497 7 to to IN cord-014597-66vd2mdu 497 8 those those DT cord-014597-66vd2mdu 497 9 obtained obtain VBN cord-014597-66vd2mdu 497 10 with with IN cord-014597-66vd2mdu 497 11 the the DT cord-014597-66vd2mdu 497 12 AktaXpress AktaXpress NNP cord-014597-66vd2mdu 497 13 at at IN cord-014597-66vd2mdu 497 14 larger large JJR cord-014597-66vd2mdu 497 15 scale scale NN cord-014597-66vd2mdu 497 16 purification purification NN cord-014597-66vd2mdu 497 17 , , , cord-014597-66vd2mdu 497 18 comparing compare VBG cord-014597-66vd2mdu 497 19 the the DT cord-014597-66vd2mdu 497 20 yield yield NN cord-014597-66vd2mdu 497 21 of of IN cord-014597-66vd2mdu 497 22 the the DT cord-014597-66vd2mdu 497 23 purification purification NN cord-014597-66vd2mdu 497 24 and and CC cord-014597-66vd2mdu 497 25 the the DT cord-014597-66vd2mdu 497 26 PQA pqa NN cord-014597-66vd2mdu 497 27 of of IN cord-014597-66vd2mdu 497 28 the the DT cord-014597-66vd2mdu 497 29 Protein Protein NNP cord-014597-66vd2mdu 497 30 - - HYPH cord-014597-66vd2mdu 497 31 A A NNP cord-014597-66vd2mdu 497 32 eluates eluate NNS cord-014597-66vd2mdu 497 33 obtained obtain VBN cord-014597-66vd2mdu 497 34 with with IN cord-014597-66vd2mdu 497 35 both both DT cord-014597-66vd2mdu 497 36 purification purification NN cord-014597-66vd2mdu 497 37 systems system NNS cord-014597-66vd2mdu 497 38 . . . cord-014597-66vd2mdu 498 1 Finally finally RB cord-014597-66vd2mdu 498 2 , , , cord-014597-66vd2mdu 498 3 we -PRON- PRP cord-014597-66vd2mdu 498 4 assessed assess VBD cord-014597-66vd2mdu 498 5 the the DT cord-014597-66vd2mdu 498 6 capability capability NN cord-014597-66vd2mdu 498 7 of of IN cord-014597-66vd2mdu 498 8 the the DT cord-014597-66vd2mdu 498 9 robot robot NN cord-014597-66vd2mdu 498 10 to to TO cord-014597-66vd2mdu 498 11 perform perform VB cord-014597-66vd2mdu 498 12 HTS HTS NNP cord-014597-66vd2mdu 498 13 of of IN cord-014597-66vd2mdu 498 14 buffer buffer NN cord-014597-66vd2mdu 498 15 and and CC cord-014597-66vd2mdu 498 16 purification purification NN cord-014597-66vd2mdu 498 17 conditions condition NNS cord-014597-66vd2mdu 498 18 , , , cord-014597-66vd2mdu 498 19 evaluating evaluate VBG cord-014597-66vd2mdu 498 20 three three CD cord-014597-66vd2mdu 498 21 different different JJ cord-014597-66vd2mdu 498 22 buffers buffer NNS cord-014597-66vd2mdu 498 23 at at IN cord-014597-66vd2mdu 498 24 different different JJ cord-014597-66vd2mdu 498 25 concentrations concentration NNS cord-014597-66vd2mdu 498 26 and and CC cord-014597-66vd2mdu 498 27 pH ph NN cord-014597-66vd2mdu 498 28 values value NNS cord-014597-66vd2mdu 498 29 , , , cord-014597-66vd2mdu 498 30 and and CC cord-014597-66vd2mdu 498 31 also also RB cord-014597-66vd2mdu 498 32 testing test VBG cord-014597-66vd2mdu 498 33 different different JJ cord-014597-66vd2mdu 498 34 loading loading NN cord-014597-66vd2mdu 498 35 column column NN cord-014597-66vd2mdu 498 36 capacities capacity NNS cord-014597-66vd2mdu 498 37 . . . cord-014597-66vd2mdu 499 1 In in IN cord-014597-66vd2mdu 499 2 this this DT cord-014597-66vd2mdu 499 3 study study NN cord-014597-66vd2mdu 499 4 we -PRON- PRP cord-014597-66vd2mdu 499 5 established establish VBD cord-014597-66vd2mdu 499 6 that that IN cord-014597-66vd2mdu 499 7 the the DT cord-014597-66vd2mdu 499 8 Tecan Tecan NNP cord-014597-66vd2mdu 499 9 can can MD cord-014597-66vd2mdu 499 10 be be VB cord-014597-66vd2mdu 499 11 used use VBN cord-014597-66vd2mdu 499 12 as as IN cord-014597-66vd2mdu 499 13 a a DT cord-014597-66vd2mdu 499 14 robust robust JJ cord-014597-66vd2mdu 499 15 platform platform NN cord-014597-66vd2mdu 499 16 for for IN cord-014597-66vd2mdu 499 17 purification purification NN cord-014597-66vd2mdu 499 18 at at IN cord-014597-66vd2mdu 499 19 small small JJ cord-014597-66vd2mdu 499 20 scale scale NN cord-014597-66vd2mdu 499 21 . . . cord-014597-66vd2mdu 500 1 We -PRON- PRP cord-014597-66vd2mdu 500 2 observed observe VBD cord-014597-66vd2mdu 500 3 similar similar JJ cord-014597-66vd2mdu 500 4 purification purification NN cord-014597-66vd2mdu 500 5 yields yield NNS cord-014597-66vd2mdu 500 6 , , , cord-014597-66vd2mdu 500 7 intra intra NNP cord-014597-66vd2mdu 500 8 and and CC cord-014597-66vd2mdu 500 9 inter inter JJ cord-014597-66vd2mdu 500 10 run run NN cord-014597-66vd2mdu 500 11 . . . cord-014597-66vd2mdu 501 1 The the DT cord-014597-66vd2mdu 501 2 analysis analysis NN cord-014597-66vd2mdu 501 3 of of IN cord-014597-66vd2mdu 501 4 the the DT cord-014597-66vd2mdu 501 5 PQA1a PQA1a NNP cord-014597-66vd2mdu 501 6 level level NN cord-014597-66vd2mdu 501 7 showed show VBD cord-014597-66vd2mdu 501 8 there there EX cord-014597-66vd2mdu 501 9 is be VBZ cord-014597-66vd2mdu 501 10 also also RB cord-014597-66vd2mdu 501 11 very very RB cord-014597-66vd2mdu 501 12 high high JJ cord-014597-66vd2mdu 501 13 reproducibility reproducibility NN cord-014597-66vd2mdu 501 14 . . . cord-014597-66vd2mdu 502 1 And and CC cord-014597-66vd2mdu 502 2 the the DT cord-014597-66vd2mdu 502 3 pH ph NN cord-014597-66vd2mdu 502 4 of of IN cord-014597-66vd2mdu 502 5 the the DT cord-014597-66vd2mdu 502 6 eluate eluate NN cord-014597-66vd2mdu 502 7 showed show VBD cord-014597-66vd2mdu 502 8 as as RB cord-014597-66vd2mdu 502 9 well well RB cord-014597-66vd2mdu 502 10 strong strong JJ cord-014597-66vd2mdu 502 11 comparability comparability NN cord-014597-66vd2mdu 502 12 as as RB cord-014597-66vd2mdu 502 13 well well RB cord-014597-66vd2mdu 502 14 . . . cord-014597-66vd2mdu 503 1 Table table NN cord-014597-66vd2mdu 503 2 1 1 CD cord-014597-66vd2mdu 503 3 shows show VBZ cord-014597-66vd2mdu 503 4 the the DT cord-014597-66vd2mdu 503 5 coefficient coefficient NN cord-014597-66vd2mdu 503 6 of of IN cord-014597-66vd2mdu 503 7 variation variation NN cord-014597-66vd2mdu 503 8 ( ( -LRB- cord-014597-66vd2mdu 503 9 CV CV NNP cord-014597-66vd2mdu 503 10 ) ) -RRB- cord-014597-66vd2mdu 503 11 of of IN cord-014597-66vd2mdu 503 12 the the DT cord-014597-66vd2mdu 503 13 yield yield NN cord-014597-66vd2mdu 503 14 , , , cord-014597-66vd2mdu 504 1 HMWS HMWS NNP cord-014597-66vd2mdu 504 2 and and CC cord-014597-66vd2mdu 504 3 eluate eluate NNP cord-014597-66vd2mdu 504 4 pH pH NNP cord-014597-66vd2mdu 504 5 are be VBP cord-014597-66vd2mdu 504 6 low low JJ cord-014597-66vd2mdu 504 7 , , , cord-014597-66vd2mdu 504 8 demonstrating demonstrate VBG cord-014597-66vd2mdu 504 9 the the DT cord-014597-66vd2mdu 504 10 good good JJ cord-014597-66vd2mdu 504 11 reproducibility reproducibility NN cord-014597-66vd2mdu 504 12 of of IN cord-014597-66vd2mdu 504 13 the the DT cord-014597-66vd2mdu 504 14 purification purification NN cord-014597-66vd2mdu 504 15 . . . cord-014597-66vd2mdu 505 1 The the DT cord-014597-66vd2mdu 505 2 strong strong JJ cord-014597-66vd2mdu 505 3 reproducibility reproducibility NN cord-014597-66vd2mdu 505 4 obtained obtain VBN cord-014597-66vd2mdu 505 5 between between IN cord-014597-66vd2mdu 505 6 the the DT cord-014597-66vd2mdu 505 7 different different JJ cord-014597-66vd2mdu 505 8 purifications purification NNS cord-014597-66vd2mdu 505 9 showed show VBD cord-014597-66vd2mdu 505 10 that that IN cord-014597-66vd2mdu 505 11 the the DT cord-014597-66vd2mdu 505 12 Tecan Tecan NNP cord-014597-66vd2mdu 505 13 and and CC cord-014597-66vd2mdu 505 14 the the DT cord-014597-66vd2mdu 505 15 AktaXpress AktaXpress NNP cord-014597-66vd2mdu 505 16 are be VBP cord-014597-66vd2mdu 505 17 similar similar JJ cord-014597-66vd2mdu 505 18 in in IN cord-014597-66vd2mdu 505 19 terms term NNS cord-014597-66vd2mdu 505 20 of of IN cord-014597-66vd2mdu 505 21 purification purification NN cord-014597-66vd2mdu 505 22 performance performance NN cord-014597-66vd2mdu 505 23 and and CC cord-014597-66vd2mdu 505 24 PQA PQA NNP cord-014597-66vd2mdu 505 25 ( ( -LRB- cord-014597-66vd2mdu 505 26 Fig Fig NNP cord-014597-66vd2mdu 505 27 . . . cord-014597-66vd2mdu 505 28 1a 1a CD cord-014597-66vd2mdu 505 29 , , , cord-014597-66vd2mdu 505 30 b b LS cord-014597-66vd2mdu 505 31 ) ) -RRB- cord-014597-66vd2mdu 505 32 . . . cord-014597-66vd2mdu 506 1 The the DT cord-014597-66vd2mdu 506 2 Tecan Tecan NNP cord-014597-66vd2mdu 506 3 is be VBZ cord-014597-66vd2mdu 506 4 a a DT cord-014597-66vd2mdu 506 5 versatile versatile JJ cord-014597-66vd2mdu 506 6 automated automate VBN cord-014597-66vd2mdu 506 7 liquid liquid NN cord-014597-66vd2mdu 506 8 handler handler NN cord-014597-66vd2mdu 506 9 allowing allow VBG cord-014597-66vd2mdu 506 10 the the DT cord-014597-66vd2mdu 506 11 screening screening NN cord-014597-66vd2mdu 506 12 of of IN cord-014597-66vd2mdu 506 13 huge huge JJ cord-014597-66vd2mdu 506 14 purification purification NN cord-014597-66vd2mdu 506 15 conditions condition NNS cord-014597-66vd2mdu 506 16 ( ( -LRB- cord-014597-66vd2mdu 506 17 Fig Fig NNP cord-014597-66vd2mdu 506 18 . . . cord-014597-66vd2mdu 506 19 1c 1c NNP cord-014597-66vd2mdu 506 20 ) ) -RRB- cord-014597-66vd2mdu 506 21 , , , cord-014597-66vd2mdu 506 22 the the DT cord-014597-66vd2mdu 506 23 possibility possibility NN cord-014597-66vd2mdu 506 24 to to TO cord-014597-66vd2mdu 506 25 purify purify VB cord-014597-66vd2mdu 506 26 large large JJ cord-014597-66vd2mdu 506 27 quantities quantity NNS cord-014597-66vd2mdu 506 28 of of IN cord-014597-66vd2mdu 506 29 samples sample NNS cord-014597-66vd2mdu 506 30 , , , cord-014597-66vd2mdu 506 31 while while IN cord-014597-66vd2mdu 506 32 the the DT cord-014597-66vd2mdu 506 33 samples sample NNS cord-014597-66vd2mdu 506 34 amount amount NN cord-014597-66vd2mdu 506 35 is be VBZ cord-014597-66vd2mdu 506 36 limited limit VBN cord-014597-66vd2mdu 506 37 . . . cord-014597-66vd2mdu 507 1 The the DT cord-014597-66vd2mdu 507 2 Tecan Tecan NNP cord-014597-66vd2mdu 507 3 has have VBZ cord-014597-66vd2mdu 507 4 the the DT cord-014597-66vd2mdu 507 5 potential potential NN cord-014597-66vd2mdu 507 6 to to TO cord-014597-66vd2mdu 507 7 purify purify VB cord-014597-66vd2mdu 507 8 more more JJR cord-014597-66vd2mdu 507 9 than than IN cord-014597-66vd2mdu 507 10 150 150 CD cord-014597-66vd2mdu 507 11 samples sample NNS cord-014597-66vd2mdu 507 12 / / SYM cord-014597-66vd2mdu 507 13 day day NN cord-014597-66vd2mdu 507 14 , , , cord-014597-66vd2mdu 507 15 reducing reduce VBG cord-014597-66vd2mdu 507 16 timelines timeline NNS cord-014597-66vd2mdu 507 17 and and CC cord-014597-66vd2mdu 507 18 allowing allow VBG cord-014597-66vd2mdu 507 19 us -PRON- PRP cord-014597-66vd2mdu 507 20 to to TO cord-014597-66vd2mdu 507 21 deliver deliver VB cord-014597-66vd2mdu 507 22 faster fast RBR cord-014597-66vd2mdu 507 23 to to IN cord-014597-66vd2mdu 507 24 the the DT cord-014597-66vd2mdu 507 25 patients patient NNS cord-014597-66vd2mdu 507 26 . . . cord-014597-66vd2mdu 508 1 Viable viable JJ cord-014597-66vd2mdu 508 2 cell cell NN cord-014597-66vd2mdu 508 3 density density NN cord-014597-66vd2mdu 508 4 monitoring monitoring NN cord-014597-66vd2mdu 508 5 in in IN cord-014597-66vd2mdu 508 6 bioreactor bioreactor NN cord-014597-66vd2mdu 508 7 with with IN cord-014597-66vd2mdu 508 8 lensless lensless NN cord-014597-66vd2mdu 508 9 imaging imaging NN cord-014597-66vd2mdu 508 10 Geoffrey Geoffrey NNP cord-014597-66vd2mdu 508 11 Monitoring Monitoring NNP cord-014597-66vd2mdu 508 12 cell cell NN cord-014597-66vd2mdu 508 13 density density NN cord-014597-66vd2mdu 508 14 and and CC cord-014597-66vd2mdu 508 15 viability viability NN cord-014597-66vd2mdu 508 16 of of IN cord-014597-66vd2mdu 508 17 mammalian mammalian JJ cord-014597-66vd2mdu 508 18 cell cell NN cord-014597-66vd2mdu 508 19 culture culture NN cord-014597-66vd2mdu 508 20 bioreactors bioreactor NNS cord-014597-66vd2mdu 508 21 is be VBZ cord-014597-66vd2mdu 508 22 a a DT cord-014597-66vd2mdu 508 23 necessary necessary JJ cord-014597-66vd2mdu 508 24 task task NN cord-014597-66vd2mdu 508 25 that that WDT cord-014597-66vd2mdu 508 26 presents present VBZ cord-014597-66vd2mdu 508 27 today today NN cord-014597-66vd2mdu 508 28 a a DT cord-014597-66vd2mdu 508 29 number number NN cord-014597-66vd2mdu 508 30 of of IN cord-014597-66vd2mdu 508 31 remaining remain VBG cord-014597-66vd2mdu 508 32 challenges challenge NNS cord-014597-66vd2mdu 508 33 . . . cord-014597-66vd2mdu 509 1 The the DT cord-014597-66vd2mdu 509 2 traditional traditional JJ cord-014597-66vd2mdu 509 3 measurement measurement NN cord-014597-66vd2mdu 509 4 for for IN cord-014597-66vd2mdu 509 5 bioreactor bioreactor NN cord-014597-66vd2mdu 509 6 cell cell NN cord-014597-66vd2mdu 509 7 count count NN cord-014597-66vd2mdu 509 8 and and CC cord-014597-66vd2mdu 509 9 viability viability NN cord-014597-66vd2mdu 509 10 rely rely VBP cord-014597-66vd2mdu 509 11 on on IN cord-014597-66vd2mdu 509 12 using use VBG cord-014597-66vd2mdu 509 13 the the DT cord-014597-66vd2mdu 509 14 Trypan Trypan NNP cord-014597-66vd2mdu 509 15 Blue Blue NNP cord-014597-66vd2mdu 509 16 exclusion exclusion NN cord-014597-66vd2mdu 509 17 method method NN cord-014597-66vd2mdu 509 18 once once RB cord-014597-66vd2mdu 509 19 a a DT cord-014597-66vd2mdu 509 20 day day NN cord-014597-66vd2mdu 509 21 . . . cord-014597-66vd2mdu 510 1 While while IN cord-014597-66vd2mdu 510 2 automatic automatic JJ cord-014597-66vd2mdu 510 3 cell cell NN cord-014597-66vd2mdu 510 4 counters counter NNS cord-014597-66vd2mdu 510 5 have have VBP cord-014597-66vd2mdu 510 6 reduced reduce VBN cord-014597-66vd2mdu 510 7 the the DT cord-014597-66vd2mdu 510 8 statistical statistical JJ cord-014597-66vd2mdu 510 9 manual manual JJ cord-014597-66vd2mdu 510 10 error error NN cord-014597-66vd2mdu 510 11 , , , cord-014597-66vd2mdu 510 12 sampling sample VBG cord-014597-66vd2mdu 510 13 the the DT cord-014597-66vd2mdu 510 14 bioreactor bioreactor NN cord-014597-66vd2mdu 510 15 remains remain VBZ cord-014597-66vd2mdu 510 16 a a DT cord-014597-66vd2mdu 510 17 contamination contamination NN cord-014597-66vd2mdu 510 18 risk risk NN cord-014597-66vd2mdu 510 19 and and CC cord-014597-66vd2mdu 510 20 is be VBZ cord-014597-66vd2mdu 510 21 prohibiting prohibit VBG cord-014597-66vd2mdu 510 22 process process NN cord-014597-66vd2mdu 510 23 control control NN cord-014597-66vd2mdu 510 24 as as IN cord-014597-66vd2mdu 510 25 the the DT cord-014597-66vd2mdu 510 26 sampled sample VBN cord-014597-66vd2mdu 510 27 volume volume NN cord-014597-66vd2mdu 510 28 becomes become VBZ cord-014597-66vd2mdu 510 29 siginficant siginficant JJ cord-014597-66vd2mdu 510 30 . . . cord-014597-66vd2mdu 511 1 Lensless Lensless NNP cord-014597-66vd2mdu 511 2 Imaging Imaging NNP cord-014597-66vd2mdu 511 3 Technology Technology NNP cord-014597-66vd2mdu 511 4 is be VBZ cord-014597-66vd2mdu 511 5 a a DT cord-014597-66vd2mdu 511 6 new new JJ cord-014597-66vd2mdu 511 7 method method NN cord-014597-66vd2mdu 511 8 for for IN cord-014597-66vd2mdu 511 9 accurately accurately RB cord-014597-66vd2mdu 511 10 determining determine VBG cord-014597-66vd2mdu 511 11 cell cell NN cord-014597-66vd2mdu 511 12 concentration concentration NN cord-014597-66vd2mdu 511 13 and and CC cord-014597-66vd2mdu 511 14 viability viability NN cord-014597-66vd2mdu 511 15 without without IN cord-014597-66vd2mdu 511 16 staining stain VBG cord-014597-66vd2mdu 511 17 . . . cord-014597-66vd2mdu 512 1 This this DT cord-014597-66vd2mdu 512 2 technique technique NN cord-014597-66vd2mdu 512 3 directly directly RB cord-014597-66vd2mdu 512 4 acquires acquire VBZ cord-014597-66vd2mdu 512 5 the the DT cord-014597-66vd2mdu 512 6 light light JJ cord-014597-66vd2mdu 512 7 diffraction diffraction NN cord-014597-66vd2mdu 512 8 properties property NNS cord-014597-66vd2mdu 512 9 of of IN cord-014597-66vd2mdu 512 10 each each DT cord-014597-66vd2mdu 512 11 individual individual JJ cord-014597-66vd2mdu 512 12 cells cell VBZ cord-014597-66vd2mdu 512 13 through through IN cord-014597-66vd2mdu 512 14 their -PRON- PRP$ cord-014597-66vd2mdu 512 15 holograms hologram NNS cord-014597-66vd2mdu 512 16 images image NNS cord-014597-66vd2mdu 512 17 without without IN cord-014597-66vd2mdu 512 18 any any DT cord-014597-66vd2mdu 512 19 objective objective NN cord-014597-66vd2mdu 512 20 , , , cord-014597-66vd2mdu 512 21 lens lens NN cord-014597-66vd2mdu 512 22 or or CC cord-014597-66vd2mdu 512 23 focus focus VB cord-014597-66vd2mdu 512 24 settings setting NNS cord-014597-66vd2mdu 512 25 . . . cord-014597-66vd2mdu 513 1 Living live VBG cord-014597-66vd2mdu 513 2 and and CC cord-014597-66vd2mdu 513 3 dead dead JJ cord-014597-66vd2mdu 513 4 cells cell NNS cord-014597-66vd2mdu 513 5 have have VBP cord-014597-66vd2mdu 513 6 significant significant JJ cord-014597-66vd2mdu 513 7 holographic holographic JJ cord-014597-66vd2mdu 513 8 patterns pattern NNS cord-014597-66vd2mdu 513 9 that that WDT cord-014597-66vd2mdu 513 10 can can MD cord-014597-66vd2mdu 513 11 be be VB cord-014597-66vd2mdu 513 12 distinguished distinguished JJ cord-014597-66vd2mdu 513 13 and and CC cord-014597-66vd2mdu 513 14 precisely precisely RB cord-014597-66vd2mdu 513 15 counted count VBN cord-014597-66vd2mdu 513 16 . . . cord-014597-66vd2mdu 514 1 Lensless lensless NN cord-014597-66vd2mdu 514 2 imaging imaging NN cord-014597-66vd2mdu 514 3 technique technique NN cord-014597-66vd2mdu 514 4 directly directly RB cord-014597-66vd2mdu 514 5 acquires acquire VBZ cord-014597-66vd2mdu 514 6 the the DT cord-014597-66vd2mdu 514 7 light light JJ cord-014597-66vd2mdu 514 8 diffraction diffraction NN cord-014597-66vd2mdu 514 9 properties property NNS cord-014597-66vd2mdu 514 10 of of IN cord-014597-66vd2mdu 514 11 each each DT cord-014597-66vd2mdu 514 12 individual individual JJ cord-014597-66vd2mdu 514 13 cells cell VBZ cord-014597-66vd2mdu 514 14 through through IN cord-014597-66vd2mdu 514 15 their -PRON- PRP$ cord-014597-66vd2mdu 514 16 holograms hologram NNS cord-014597-66vd2mdu 514 17 images image NNS cord-014597-66vd2mdu 514 18 without without IN cord-014597-66vd2mdu 514 19 any any DT cord-014597-66vd2mdu 514 20 objective objective NN cord-014597-66vd2mdu 514 21 , , , cord-014597-66vd2mdu 514 22 lens lens NN cord-014597-66vd2mdu 514 23 or or CC cord-014597-66vd2mdu 514 24 focus focus VB cord-014597-66vd2mdu 514 25 settings setting NNS cord-014597-66vd2mdu 514 26 . . . cord-014597-66vd2mdu 515 1 Living live VBG cord-014597-66vd2mdu 515 2 and and CC cord-014597-66vd2mdu 515 3 dead dead JJ cord-014597-66vd2mdu 515 4 cells cell NNS cord-014597-66vd2mdu 515 5 have have VBP cord-014597-66vd2mdu 515 6 significant significant JJ cord-014597-66vd2mdu 515 7 holographic holographic JJ cord-014597-66vd2mdu 515 8 patterns pattern NNS cord-014597-66vd2mdu 515 9 that that WDT cord-014597-66vd2mdu 515 10 can can MD cord-014597-66vd2mdu 515 11 be be VB cord-014597-66vd2mdu 515 12 distinguished distinguished JJ cord-014597-66vd2mdu 515 13 and and CC cord-014597-66vd2mdu 515 14 precisely precisely RB cord-014597-66vd2mdu 515 15 counted count VBN cord-014597-66vd2mdu 515 16 . . . cord-014597-66vd2mdu 516 1 We -PRON- PRP cord-014597-66vd2mdu 516 2 compare compare VBP cord-014597-66vd2mdu 516 3 cell cell NN cord-014597-66vd2mdu 516 4 counts count NNS cord-014597-66vd2mdu 516 5 and and CC cord-014597-66vd2mdu 516 6 viability viability NN cord-014597-66vd2mdu 516 7 between between IN cord-014597-66vd2mdu 516 8 the the DT cord-014597-66vd2mdu 516 9 reference reference NN cord-014597-66vd2mdu 516 10 method method NN cord-014597-66vd2mdu 516 11 and and CC cord-014597-66vd2mdu 516 12 our -PRON- PRP$ cord-014597-66vd2mdu 516 13 Lensless Lensless NNP cord-014597-66vd2mdu 516 14 Imaging Imaging NNP cord-014597-66vd2mdu 516 15 device device NN cord-014597-66vd2mdu 516 16 , , , cord-014597-66vd2mdu 516 17 the the DT cord-014597-66vd2mdu 516 18 Cytonote Cytonote NNP cord-014597-66vd2mdu 516 19 counter counter NN cord-014597-66vd2mdu 516 20 . . . cord-014597-66vd2mdu 517 1 Measures measure NNS cord-014597-66vd2mdu 517 2 are be VBP cord-014597-66vd2mdu 517 3 performed perform VBN cord-014597-66vd2mdu 517 4 once once RB cord-014597-66vd2mdu 517 5 a a DT cord-014597-66vd2mdu 517 6 day day NN cord-014597-66vd2mdu 517 7 on on IN cord-014597-66vd2mdu 517 8 samples sample NNS cord-014597-66vd2mdu 517 9 from from IN cord-014597-66vd2mdu 517 10 12 12 CD cord-014597-66vd2mdu 517 11 bioreactors bioreactor NNS cord-014597-66vd2mdu 517 12 , , , cord-014597-66vd2mdu 517 13 from from IN cord-014597-66vd2mdu 517 14 the the DT cord-014597-66vd2mdu 517 15 inoculation inoculation NN cord-014597-66vd2mdu 517 16 to to IN cord-014597-66vd2mdu 517 17 the the DT cord-014597-66vd2mdu 517 18 end end NN cord-014597-66vd2mdu 517 19 of of IN cord-014597-66vd2mdu 517 20 the the DT cord-014597-66vd2mdu 517 21 culture culture NN cord-014597-66vd2mdu 517 22 . . . cord-014597-66vd2mdu 518 1 We -PRON- PRP cord-014597-66vd2mdu 518 2 also also RB cord-014597-66vd2mdu 518 3 assessed assess VBD cord-014597-66vd2mdu 518 4 the the DT cord-014597-66vd2mdu 518 5 repeatability repeatability NN cord-014597-66vd2mdu 518 6 of of IN cord-014597-66vd2mdu 518 7 our -PRON- PRP$ cord-014597-66vd2mdu 518 8 method method NN cord-014597-66vd2mdu 518 9 . . . cord-014597-66vd2mdu 519 1 Another another DT cord-014597-66vd2mdu 519 2 Lensless Lensless NNP cord-014597-66vd2mdu 519 3 Imaging Imaging NNP cord-014597-66vd2mdu 519 4 prototype prototype NN cord-014597-66vd2mdu 519 5 is be VBZ cord-014597-66vd2mdu 519 6 setup setup NN cord-014597-66vd2mdu 519 7 as as IN cord-014597-66vd2mdu 519 8 a a DT cord-014597-66vd2mdu 519 9 measurement measurement NN cord-014597-66vd2mdu 519 10 chamber chamber NN cord-014597-66vd2mdu 519 11 directly directly RB cord-014597-66vd2mdu 519 12 connected connect VBN cord-014597-66vd2mdu 519 13 to to IN cord-014597-66vd2mdu 519 14 a a DT cord-014597-66vd2mdu 519 15 perfusion perfusion NN cord-014597-66vd2mdu 519 16 bioreactor bioreactor NN cord-014597-66vd2mdu 519 17 , , , cord-014597-66vd2mdu 519 18 for for IN cord-014597-66vd2mdu 519 19 continuously continuously RB cord-014597-66vd2mdu 519 20 receiving receive VBG cord-014597-66vd2mdu 519 21 the the DT cord-014597-66vd2mdu 519 22 bioreactor bioreactor NN cord-014597-66vd2mdu 519 23 broth broth NN cord-014597-66vd2mdu 519 24 , , , cord-014597-66vd2mdu 519 25 and and CC cord-014597-66vd2mdu 519 26 therefore therefore RB cord-014597-66vd2mdu 519 27 reproducing reproduce VBG cord-014597-66vd2mdu 519 28 an an DT cord-014597-66vd2mdu 519 29 in in IN cord-014597-66vd2mdu 519 30 situ situ JJ cord-014597-66vd2mdu 519 31 measure measure NN cord-014597-66vd2mdu 519 32 . . . cord-014597-66vd2mdu 520 1 With with IN cord-014597-66vd2mdu 520 2 a a DT cord-014597-66vd2mdu 520 3 concentration concentration NN cord-014597-66vd2mdu 520 4 range range NN cord-014597-66vd2mdu 520 5 up up IN cord-014597-66vd2mdu 520 6 to to IN cord-014597-66vd2mdu 520 7 40x10 40x10 CD cord-014597-66vd2mdu 520 8 6 6 CD cord-014597-66vd2mdu 520 9 cells cell NNS cord-014597-66vd2mdu 520 10 / / SYM cord-014597-66vd2mdu 520 11 ml ml NN cord-014597-66vd2mdu 521 1 ( ( -LRB- cord-014597-66vd2mdu 521 2 Fig Fig NNP cord-014597-66vd2mdu 521 3 . . NNP cord-014597-66vd2mdu 521 4 1 1 CD cord-014597-66vd2mdu 521 5 ) ) -RRB- cord-014597-66vd2mdu 522 1 and and CC cord-014597-66vd2mdu 522 2 viability viability NN cord-014597-66vd2mdu 522 3 range range NN cord-014597-66vd2mdu 522 4 at at IN cord-014597-66vd2mdu 522 5 75 75 CD cord-014597-66vd2mdu 522 6 - - SYM cord-014597-66vd2mdu 522 7 100 100 CD cord-014597-66vd2mdu 522 8 % % NN cord-014597-66vd2mdu 523 1 , , , cord-014597-66vd2mdu 523 2 we -PRON- PRP cord-014597-66vd2mdu 523 3 obtained obtain VBD cord-014597-66vd2mdu 523 4 a a DT cord-014597-66vd2mdu 523 5 correlation correlation NN cord-014597-66vd2mdu 523 6 factor factor NN cord-014597-66vd2mdu 523 7 of of IN cord-014597-66vd2mdu 523 8 0.98 0.98 CD cord-014597-66vd2mdu 523 9 between between IN cord-014597-66vd2mdu 523 10 the the DT cord-014597-66vd2mdu 523 11 two two CD cord-014597-66vd2mdu 523 12 compared compare VBN cord-014597-66vd2mdu 523 13 methods method NNS cord-014597-66vd2mdu 523 14 . . . cord-014597-66vd2mdu 524 1 The the DT cord-014597-66vd2mdu 524 2 large large JJ cord-014597-66vd2mdu 524 3 field field NN cord-014597-66vd2mdu 524 4 of of IN cord-014597-66vd2mdu 524 5 view view NN cord-014597-66vd2mdu 524 6 allows allow VBZ cord-014597-66vd2mdu 524 7 the the DT cord-014597-66vd2mdu 524 8 analyze analyze NN cord-014597-66vd2mdu 524 9 of of IN cord-014597-66vd2mdu 524 10 several several JJ cord-014597-66vd2mdu 524 11 thousand thousand CD cord-014597-66vd2mdu 524 12 cells cell NNS cord-014597-66vd2mdu 524 13 within within IN cord-014597-66vd2mdu 524 14 a a DT cord-014597-66vd2mdu 524 15 single single JJ cord-014597-66vd2mdu 524 16 image image NN cord-014597-66vd2mdu 524 17 , , , cord-014597-66vd2mdu 524 18 keeping keep VBG cord-014597-66vd2mdu 524 19 the the DT cord-014597-66vd2mdu 524 20 statistical statistical JJ cord-014597-66vd2mdu 524 21 variability variability NN cord-014597-66vd2mdu 524 22 of of IN cord-014597-66vd2mdu 524 23 the the DT cord-014597-66vd2mdu 524 24 measure measure NN cord-014597-66vd2mdu 524 25 as as RB cord-014597-66vd2mdu 524 26 low low JJ cord-014597-66vd2mdu 524 27 as as IN cord-014597-66vd2mdu 524 28 3 3 CD cord-014597-66vd2mdu 524 29 % % NN cord-014597-66vd2mdu 524 30 . . . cord-014597-66vd2mdu 525 1 Our -PRON- PRP$ cord-014597-66vd2mdu 525 2 measurement measurement NN cord-014597-66vd2mdu 525 3 chamber chamber NN cord-014597-66vd2mdu 525 4 prototype prototype NN cord-014597-66vd2mdu 525 5 has have VBZ cord-014597-66vd2mdu 525 6 demonstarted demonstarte VBN cord-014597-66vd2mdu 525 7 its -PRON- PRP$ cord-014597-66vd2mdu 525 8 capability capability NN cord-014597-66vd2mdu 525 9 for for IN cord-014597-66vd2mdu 525 10 continuous continuous JJ cord-014597-66vd2mdu 525 11 Viable viable JJ cord-014597-66vd2mdu 525 12 Cell cell NN cord-014597-66vd2mdu 525 13 Density density NN cord-014597-66vd2mdu 525 14 and and CC cord-014597-66vd2mdu 525 15 viability viability NN cord-014597-66vd2mdu 525 16 monitoring monitoring NN cord-014597-66vd2mdu 525 17 . . . cord-014597-66vd2mdu 526 1 We -PRON- PRP cord-014597-66vd2mdu 526 2 are be VBP cord-014597-66vd2mdu 526 3 now now RB cord-014597-66vd2mdu 526 4 working work VBG cord-014597-66vd2mdu 526 5 at at IN cord-014597-66vd2mdu 526 6 designing design VBG cord-014597-66vd2mdu 526 7 a a DT cord-014597-66vd2mdu 526 8 steam steam NN cord-014597-66vd2mdu 526 9 strerilizable strerilizable JJ cord-014597-66vd2mdu 526 10 probe probe NN cord-014597-66vd2mdu 526 11 , , , cord-014597-66vd2mdu 526 12 and and CC cord-014597-66vd2mdu 526 13 we -PRON- PRP cord-014597-66vd2mdu 526 14 envision envision VBP cord-014597-66vd2mdu 526 15 Lensless Lensless NNP cord-014597-66vd2mdu 526 16 Imaging Imaging NNP cord-014597-66vd2mdu 526 17 to to TO cord-014597-66vd2mdu 526 18 become become VB cord-014597-66vd2mdu 526 19 the the DT cord-014597-66vd2mdu 526 20 future future JJ cord-014597-66vd2mdu 526 21 method method NN cord-014597-66vd2mdu 526 22 of of IN cord-014597-66vd2mdu 526 23 choice choice NN cord-014597-66vd2mdu 526 24 for for IN cord-014597-66vd2mdu 526 25 on on IN cord-014597-66vd2mdu 526 26 - - HYPH cord-014597-66vd2mdu 526 27 line line NN cord-014597-66vd2mdu 526 28 monitoring monitoring NN cord-014597-66vd2mdu 526 29 of of IN cord-014597-66vd2mdu 526 30 suspension suspension NN cord-014597-66vd2mdu 526 31 cells cell NNS cord-014597-66vd2mdu 526 32 cultures culture NNS cord-014597-66vd2mdu 526 33 . . . cord-014597-66vd2mdu 527 1 Lensless Lensless NNP cord-014597-66vd2mdu 527 2 Imaging Imaging NNP cord-014597-66vd2mdu 527 3 Technology Technology NNP cord-014597-66vd2mdu 527 4 is be VBZ cord-014597-66vd2mdu 527 5 capable capable JJ cord-014597-66vd2mdu 527 6 of of IN cord-014597-66vd2mdu 527 7 accurately accurately RB cord-014597-66vd2mdu 527 8 and and CC cord-014597-66vd2mdu 527 9 precisely precisely RB cord-014597-66vd2mdu 527 10 monitoring monitor VBG cord-014597-66vd2mdu 527 11 Viable viable JJ cord-014597-66vd2mdu 527 12 Cell cell NN cord-014597-66vd2mdu 527 13 Density density NN cord-014597-66vd2mdu 527 14 and and CC cord-014597-66vd2mdu 527 15 Viability Viability NNP cord-014597-66vd2mdu 527 16 with with IN cord-014597-66vd2mdu 527 17 a a DT cord-014597-66vd2mdu 527 18 combination combination NN cord-014597-66vd2mdu 527 19 of of IN cord-014597-66vd2mdu 527 20 significant significant JJ cord-014597-66vd2mdu 527 21 advantages advantage NNS cord-014597-66vd2mdu 527 22 starting start VBG cord-014597-66vd2mdu 527 23 from from IN cord-014597-66vd2mdu 527 24 low low JJ cord-014597-66vd2mdu 527 25 sample sample NN cord-014597-66vd2mdu 527 26 volume volume NN cord-014597-66vd2mdu 527 27 use use NN cord-014597-66vd2mdu 527 28 , , , cord-014597-66vd2mdu 527 29 label label VB cord-014597-66vd2mdu 527 30 free free JJ cord-014597-66vd2mdu 527 31 detection detection NN cord-014597-66vd2mdu 527 32 , , , cord-014597-66vd2mdu 527 33 quick quick JJ cord-014597-66vd2mdu 527 34 measure measure NN cord-014597-66vd2mdu 527 35 , , , cord-014597-66vd2mdu 527 36 simple simple JJ cord-014597-66vd2mdu 527 37 device device NN cord-014597-66vd2mdu 527 38 , , , cord-014597-66vd2mdu 527 39 to to IN cord-014597-66vd2mdu 527 40 high high JJ cord-014597-66vd2mdu 527 41 number number NN cord-014597-66vd2mdu 527 42 of of IN cord-014597-66vd2mdu 527 43 cell cell NN cord-014597-66vd2mdu 527 44 analyzed analyze VBN cord-014597-66vd2mdu 527 45 which which WDT cord-014597-66vd2mdu 527 46 let let VBD cord-014597-66vd2mdu 527 47 us -PRON- PRP cord-014597-66vd2mdu 527 48 think think VB cord-014597-66vd2mdu 527 49 that that IN cord-014597-66vd2mdu 527 50 it -PRON- PRP cord-014597-66vd2mdu 527 51 is be VBZ cord-014597-66vd2mdu 527 52 a a DT cord-014597-66vd2mdu 527 53 good good JJ cord-014597-66vd2mdu 527 54 candidate candidate NN cord-014597-66vd2mdu 527 55 for for IN cord-014597-66vd2mdu 527 56 very very RB cord-014597-66vd2mdu 527 57 small- small- JJ cord-014597-66vd2mdu 528 1 Comparison comparison NN cord-014597-66vd2mdu 528 2 between between IN cord-014597-66vd2mdu 528 3 both both DT cord-014597-66vd2mdu 528 4 purification purification NN cord-014597-66vd2mdu 528 5 systems system NNS cord-014597-66vd2mdu 528 6 and and CC cord-014597-66vd2mdu 528 7 the the DT cord-014597-66vd2mdu 528 8 ability ability NN cord-014597-66vd2mdu 528 9 of of IN cord-014597-66vd2mdu 528 10 the the DT cord-014597-66vd2mdu 528 11 system system NN cord-014597-66vd2mdu 528 12 to to TO cord-014597-66vd2mdu 528 13 be be VB cord-014597-66vd2mdu 528 14 used use VBN cord-014597-66vd2mdu 528 15 as as IN cord-014597-66vd2mdu 528 16 a a DT cord-014597-66vd2mdu 528 17 high high JJ cord-014597-66vd2mdu 528 18 throughput throughput NN cord-014597-66vd2mdu 528 19 tools tool NNS cord-014597-66vd2mdu 528 20 for for IN cord-014597-66vd2mdu 528 21 buffers buffer NNS cord-014597-66vd2mdu 528 22 screening screen VBG cord-014597-66vd2mdu 528 23 . . . cord-014597-66vd2mdu 529 1 a a DT cord-014597-66vd2mdu 529 2 Purification purification NN cord-014597-66vd2mdu 529 3 yield yield NN cord-014597-66vd2mdu 529 4 ( ( -LRB- cord-014597-66vd2mdu 529 5 % % NN cord-014597-66vd2mdu 529 6 ) ) -RRB- cord-014597-66vd2mdu 529 7 . . . cord-014597-66vd2mdu 530 1 b b LS cord-014597-66vd2mdu 530 2 PQA1.a PQA1.a NNP cord-014597-66vd2mdu 530 3 ( ( -LRB- cord-014597-66vd2mdu 530 4 normalized normalize VBN cord-014597-66vd2mdu 530 5 ) ) -RRB- cord-014597-66vd2mdu 530 6 . . . cord-014597-66vd2mdu 531 1 c c LS cord-014597-66vd2mdu 531 2 Impact Impact NNP cord-014597-66vd2mdu 531 3 of of IN cord-014597-66vd2mdu 531 4 the the DT cord-014597-66vd2mdu 531 5 pH ph NN cord-014597-66vd2mdu 531 6 and and CC cord-014597-66vd2mdu 531 7 buffer buffer NN cord-014597-66vd2mdu 531 8 concentration concentration NN cord-014597-66vd2mdu 531 9 on on IN cord-014597-66vd2mdu 531 10 the the DT cord-014597-66vd2mdu 531 11 PQA1.a PQA1.a NNP cord-014597-66vd2mdu 531 12 scale scale NN cord-014597-66vd2mdu 531 13 bioreactor bioreactor NN cord-014597-66vd2mdu 531 14 and and CC cord-014597-66vd2mdu 531 15 high high JJ cord-014597-66vd2mdu 531 16 - - HYPH cord-014597-66vd2mdu 531 17 throughput throughput NN cord-014597-66vd2mdu 531 18 measures measure NNS cord-014597-66vd2mdu 531 19 . . . cord-014597-66vd2mdu 532 1 Its -PRON- PRP$ cord-014597-66vd2mdu 532 2 high high JJ cord-014597-66vd2mdu 532 3 repeatability repeatability NN cord-014597-66vd2mdu 532 4 is be VBZ cord-014597-66vd2mdu 532 5 also also RB cord-014597-66vd2mdu 532 6 a a DT cord-014597-66vd2mdu 532 7 key key JJ cord-014597-66vd2mdu 532 8 parameters parameter NNS cord-014597-66vd2mdu 532 9 in in IN cord-014597-66vd2mdu 532 10 the the DT cord-014597-66vd2mdu 532 11 effort effort NN cord-014597-66vd2mdu 532 12 to to TO cord-014597-66vd2mdu 532 13 narrow narrow VB cord-014597-66vd2mdu 532 14 batch batch NN cord-014597-66vd2mdu 532 15 to to TO cord-014597-66vd2mdu 532 16 batch batch VB cord-014597-66vd2mdu 532 17 deviations deviation NNS cord-014597-66vd2mdu 532 18 . . . cord-014597-66vd2mdu 533 1 In in IN cord-014597-66vd2mdu 533 2 addition addition NN cord-014597-66vd2mdu 533 3 we -PRON- PRP cord-014597-66vd2mdu 533 4 demonstrate demonstrate VBP cord-014597-66vd2mdu 533 5 that that IN cord-014597-66vd2mdu 533 6 this this DT cord-014597-66vd2mdu 533 7 technique technique NN cord-014597-66vd2mdu 533 8 is be VBZ cord-014597-66vd2mdu 533 9 potentially potentially RB cord-014597-66vd2mdu 533 10 powerful powerful JJ cord-014597-66vd2mdu 533 11 for for IN cord-014597-66vd2mdu 533 12 in in IN cord-014597-66vd2mdu 533 13 - - HYPH cord-014597-66vd2mdu 533 14 line line NN cord-014597-66vd2mdu 533 15 and and CC cord-014597-66vd2mdu 533 16 continuous continuous JJ cord-014597-66vd2mdu 533 17 monitoring monitoring NN cord-014597-66vd2mdu 533 18 of of IN cord-014597-66vd2mdu 533 19 a a DT cord-014597-66vd2mdu 533 20 lab lab NN cord-014597-66vd2mdu 533 21 bioreactor bioreactor NN cord-014597-66vd2mdu 533 22 . . . cord-014597-66vd2mdu 534 1 We -PRON- PRP cord-014597-66vd2mdu 534 2 envision envision VBP cord-014597-66vd2mdu 534 3 Lensless Lensless NNP cord-014597-66vd2mdu 534 4 Imaging Imaging NNP cord-014597-66vd2mdu 534 5 to to TO cord-014597-66vd2mdu 534 6 become become VB cord-014597-66vd2mdu 534 7 the the DT cord-014597-66vd2mdu 534 8 future future JJ cord-014597-66vd2mdu 534 9 method method NN cord-014597-66vd2mdu 534 10 of of IN cord-014597-66vd2mdu 534 11 choice choice NN cord-014597-66vd2mdu 534 12 for for IN cord-014597-66vd2mdu 534 13 on on IN cord-014597-66vd2mdu 534 14 - - HYPH cord-014597-66vd2mdu 534 15 line line NN cord-014597-66vd2mdu 534 16 and and CC cord-014597-66vd2mdu 534 17 in in IN cord-014597-66vd2mdu 534 18 - - HYPH cord-014597-66vd2mdu 534 19 situ situ JJ cord-014597-66vd2mdu 534 20 monitoring monitoring NN cord-014597-66vd2mdu 534 21 of of IN cord-014597-66vd2mdu 534 22 suspension suspension NN cord-014597-66vd2mdu 534 23 cells cell NNS cord-014597-66vd2mdu 534 24 and and CC cord-014597-66vd2mdu 534 25 a a DT cord-014597-66vd2mdu 534 26 perfect perfect JJ cord-014597-66vd2mdu 534 27 tool tool NN cord-014597-66vd2mdu 534 28 for for IN cord-014597-66vd2mdu 534 29 process process NN cord-014597-66vd2mdu 534 30 control control NN cord-014597-66vd2mdu 534 31 in in IN cord-014597-66vd2mdu 534 32 fed fed NNP cord-014597-66vd2mdu 534 33 - - HYPH cord-014597-66vd2mdu 534 34 batch batch NN cord-014597-66vd2mdu 534 35 or or CC cord-014597-66vd2mdu 534 36 perfusion perfusion NN cord-014597-66vd2mdu 534 37 mode mode NN cord-014597-66vd2mdu 534 38 in in IN cord-014597-66vd2mdu 534 39 single single JJ cord-014597-66vd2mdu 534 40 - - HYPH cord-014597-66vd2mdu 534 41 use use NN cord-014597-66vd2mdu 534 42 bioreactors bioreactor NNS cord-014597-66vd2mdu 534 43 or or CC cord-014597-66vd2mdu 534 44 traditional traditional JJ cord-014597-66vd2mdu 534 45 steam steam NN cord-014597-66vd2mdu 534 46 sterilized sterilize VBN cord-014597-66vd2mdu 534 47 vessels vessel NNS cord-014597-66vd2mdu 534 48 . . . cord-014597-66vd2mdu 535 1 It -PRON- PRP cord-014597-66vd2mdu 535 2 can can MD cord-014597-66vd2mdu 535 3 certainly certainly RB cord-014597-66vd2mdu 535 4 become become VB cord-014597-66vd2mdu 535 5 the the DT cord-014597-66vd2mdu 535 6 first first JJ cord-014597-66vd2mdu 535 7 VCD vcd NN cord-014597-66vd2mdu 535 8 measurement measurement NN cord-014597-66vd2mdu 535 9 technique technique NN cord-014597-66vd2mdu 535 10 to to TO cord-014597-66vd2mdu 535 11 work work VB cord-014597-66vd2mdu 535 12 from from IN cord-014597-66vd2mdu 535 13 cell cell NN cord-014597-66vd2mdu 535 14 line line NN cord-014597-66vd2mdu 535 15 engineering engineering NN cord-014597-66vd2mdu 535 16 , , , cord-014597-66vd2mdu 535 17 to to TO cord-014597-66vd2mdu 535 18 process process VB cord-014597-66vd2mdu 535 19 development development NN cord-014597-66vd2mdu 535 20 , , , cord-014597-66vd2mdu 535 21 pilot pilot NN cord-014597-66vd2mdu 535 22 scale scale NN cord-014597-66vd2mdu 535 23 , , , cord-014597-66vd2mdu 535 24 and and CC cord-014597-66vd2mdu 535 25 up up IN cord-014597-66vd2mdu 535 26 to to IN cord-014597-66vd2mdu 535 27 manufacturing manufacturing NN cord-014597-66vd2mdu 535 28 scale scale NN cord-014597-66vd2mdu 535 29 . . . cord-014597-66vd2mdu 536 1 Time time NN cord-014597-66vd2mdu 536 2 - - HYPH cord-014597-66vd2mdu 536 3 dependent dependent JJ cord-014597-66vd2mdu 536 4 product product NN cord-014597-66vd2mdu 536 5 heterogeneity heterogeneity NN cord-014597-66vd2mdu 536 6 in in IN cord-014597-66vd2mdu 536 7 mammalian mammalian JJ cord-014597-66vd2mdu 536 8 cell cell NN cord-014597-66vd2mdu 536 9 fermentation fermentation NN cord-014597-66vd2mdu 536 10 processes process NNS cord-014597-66vd2mdu 537 1 Background background VB cord-014597-66vd2mdu 537 2 A a DT cord-014597-66vd2mdu 537 3 consistent consistent JJ cord-014597-66vd2mdu 537 4 product product NN cord-014597-66vd2mdu 537 5 quality quality NN cord-014597-66vd2mdu 537 6 is be VBZ cord-014597-66vd2mdu 537 7 a a DT cord-014597-66vd2mdu 537 8 major major JJ cord-014597-66vd2mdu 537 9 goal goal NN cord-014597-66vd2mdu 537 10 in in IN cord-014597-66vd2mdu 537 11 the the DT cord-014597-66vd2mdu 537 12 production production NN cord-014597-66vd2mdu 537 13 of of IN cord-014597-66vd2mdu 537 14 biotherapeutics biotherapeutic NNS cord-014597-66vd2mdu 537 15 , , , cord-014597-66vd2mdu 537 16 especially especially RB cord-014597-66vd2mdu 537 17 recombinant recombinant JJ cord-014597-66vd2mdu 537 18 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 537 19 . . . cord-014597-66vd2mdu 538 1 Whereas whereas IN cord-014597-66vd2mdu 538 2 it -PRON- PRP cord-014597-66vd2mdu 538 3 is be VBZ cord-014597-66vd2mdu 538 4 unlikely unlikely JJ cord-014597-66vd2mdu 538 5 that that IN cord-014597-66vd2mdu 538 6 the the DT cord-014597-66vd2mdu 538 7 polypeptide polypeptide NN cord-014597-66vd2mdu 538 8 chain chain NN cord-014597-66vd2mdu 538 9 changes change NNS cord-014597-66vd2mdu 538 10 during during IN cord-014597-66vd2mdu 538 11 a a DT cord-014597-66vd2mdu 538 12 production production NN cord-014597-66vd2mdu 538 13 process process NN cord-014597-66vd2mdu 538 14 , , , cord-014597-66vd2mdu 538 15 posttranslational posttranslational JJ cord-014597-66vd2mdu 538 16 modifications modification NNS cord-014597-66vd2mdu 538 17 and and CC cord-014597-66vd2mdu 538 18 protein protein NN cord-014597-66vd2mdu 538 19 folding folding NN cord-014597-66vd2mdu 538 20 are be VBP cord-014597-66vd2mdu 538 21 sensitive sensitive JJ cord-014597-66vd2mdu 538 22 to to IN cord-014597-66vd2mdu 538 23 fluctuations fluctuation NNS cord-014597-66vd2mdu 538 24 in in IN cord-014597-66vd2mdu 538 25 parameters parameter NNS cord-014597-66vd2mdu 538 26 and and CC cord-014597-66vd2mdu 538 27 conditions condition NNS cord-014597-66vd2mdu 538 28 . . . cord-014597-66vd2mdu 539 1 Here here RB cord-014597-66vd2mdu 539 2 we -PRON- PRP cord-014597-66vd2mdu 539 3 focus focus VBP cord-014597-66vd2mdu 539 4 on on IN cord-014597-66vd2mdu 539 5 protein protein NN cord-014597-66vd2mdu 539 6 glycosylation glycosylation NN cord-014597-66vd2mdu 539 7 as as IN cord-014597-66vd2mdu 539 8 one one CD cord-014597-66vd2mdu 539 9 important important JJ cord-014597-66vd2mdu 539 10 indication indication NN cord-014597-66vd2mdu 539 11 for for IN cord-014597-66vd2mdu 539 12 product product NN cord-014597-66vd2mdu 539 13 quality quality NN cord-014597-66vd2mdu 539 14 [ [ -LRB- cord-014597-66vd2mdu 539 15 1 1 CD cord-014597-66vd2mdu 539 16 ] ] -RRB- cord-014597-66vd2mdu 539 17 . . . cord-014597-66vd2mdu 540 1 During during IN cord-014597-66vd2mdu 540 2 a a DT cord-014597-66vd2mdu 540 3 batch batch NN cord-014597-66vd2mdu 540 4 process process NN cord-014597-66vd2mdu 540 5 conditions condition NNS cord-014597-66vd2mdu 540 6 change change VBP cord-014597-66vd2mdu 540 7 continuously continuously RB cord-014597-66vd2mdu 540 8 . . . cord-014597-66vd2mdu 541 1 At at IN cord-014597-66vd2mdu 541 2 the the DT cord-014597-66vd2mdu 541 3 beginning beginning NN cord-014597-66vd2mdu 541 4 , , , cord-014597-66vd2mdu 541 5 the the DT cord-014597-66vd2mdu 541 6 supply supply NN cord-014597-66vd2mdu 541 7 situation situation NN cord-014597-66vd2mdu 541 8 for for IN cord-014597-66vd2mdu 541 9 the the DT cord-014597-66vd2mdu 541 10 cell cell NN cord-014597-66vd2mdu 541 11 is be VBZ cord-014597-66vd2mdu 541 12 excellent excellent JJ cord-014597-66vd2mdu 541 13 , , , cord-014597-66vd2mdu 541 14 but but CC cord-014597-66vd2mdu 541 15 the the DT cord-014597-66vd2mdu 541 16 secreted secrete VBN cord-014597-66vd2mdu 541 17 material material NN cord-014597-66vd2mdu 541 18 stays stay VBZ cord-014597-66vd2mdu 541 19 a a DT cord-014597-66vd2mdu 541 20 long long JJ cord-014597-66vd2mdu 541 21 time time NN cord-014597-66vd2mdu 541 22 in in IN cord-014597-66vd2mdu 541 23 the the DT cord-014597-66vd2mdu 541 24 culture culture NN cord-014597-66vd2mdu 541 25 fluid fluid NN cord-014597-66vd2mdu 541 26 . . . cord-014597-66vd2mdu 542 1 Later later RB cord-014597-66vd2mdu 542 2 during during IN cord-014597-66vd2mdu 542 3 cultivation cultivation NN cord-014597-66vd2mdu 542 4 substrate substrate NN cord-014597-66vd2mdu 542 5 provision provision NN cord-014597-66vd2mdu 542 6 decreases decrease NNS cord-014597-66vd2mdu 542 7 , , , cord-014597-66vd2mdu 542 8 whereas whereas IN cord-014597-66vd2mdu 542 9 the the DT cord-014597-66vd2mdu 542 10 exposition exposition NN cord-014597-66vd2mdu 542 11 time time NN cord-014597-66vd2mdu 542 12 of of IN cord-014597-66vd2mdu 542 13 the the DT cord-014597-66vd2mdu 542 14 protein protein NN cord-014597-66vd2mdu 542 15 to to IN cord-014597-66vd2mdu 542 16 the the DT cord-014597-66vd2mdu 542 17 culture culture NN cord-014597-66vd2mdu 542 18 fluid fluid NN cord-014597-66vd2mdu 542 19 is be VBZ cord-014597-66vd2mdu 542 20 much much RB cord-014597-66vd2mdu 542 21 shorter short JJR cord-014597-66vd2mdu 542 22 . . . cord-014597-66vd2mdu 543 1 Altogether altogether RB cord-014597-66vd2mdu 543 2 this this DT cord-014597-66vd2mdu 543 3 leads lead VBZ cord-014597-66vd2mdu 543 4 to to IN cord-014597-66vd2mdu 543 5 product product VB cord-014597-66vd2mdu 543 6 heterogeneity heterogeneity NN cord-014597-66vd2mdu 543 7 of of IN cord-014597-66vd2mdu 543 8 the the DT cord-014597-66vd2mdu 543 9 secreted secrete VBN cord-014597-66vd2mdu 543 10 protein protein NN cord-014597-66vd2mdu 543 11 during during IN cord-014597-66vd2mdu 543 12 a a DT cord-014597-66vd2mdu 543 13 batch batch NN cord-014597-66vd2mdu 543 14 culture culture NN cord-014597-66vd2mdu 543 15 . . . cord-014597-66vd2mdu 544 1 Four four CD cord-014597-66vd2mdu 544 2 different different JJ cord-014597-66vd2mdu 544 3 cell cell NN cord-014597-66vd2mdu 544 4 lines line NNS cord-014597-66vd2mdu 544 5 , , , cord-014597-66vd2mdu 544 6 two two CD cord-014597-66vd2mdu 544 7 of of IN cord-014597-66vd2mdu 544 8 human human JJ cord-014597-66vd2mdu 544 9 origin origin NN cord-014597-66vd2mdu 544 10 and and CC cord-014597-66vd2mdu 544 11 two two CD cord-014597-66vd2mdu 544 12 CHO CHO NNP cord-014597-66vd2mdu 544 13 clones clone NNS cord-014597-66vd2mdu 544 14 , , , cord-014597-66vd2mdu 544 15 producing produce VBG cord-014597-66vd2mdu 544 16 four four CD cord-014597-66vd2mdu 544 17 different different JJ cord-014597-66vd2mdu 544 18 recombinant recombinant JJ cord-014597-66vd2mdu 544 19 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 544 20 were be VBD cord-014597-66vd2mdu 544 21 investigated investigate VBN cord-014597-66vd2mdu 544 22 in in IN cord-014597-66vd2mdu 544 23 this this DT cord-014597-66vd2mdu 544 24 study study NN cord-014597-66vd2mdu 544 25 . . . cord-014597-66vd2mdu 545 1 Together together RB cord-014597-66vd2mdu 545 2 with with IN cord-014597-66vd2mdu 545 3 their -PRON- PRP$ cord-014597-66vd2mdu 545 4 respective respective JJ cord-014597-66vd2mdu 545 5 parental parental JJ cord-014597-66vd2mdu 545 6 cell cell NN cord-014597-66vd2mdu 545 7 line line NN cord-014597-66vd2mdu 545 8 the the DT cord-014597-66vd2mdu 545 9 clones clone NNS cord-014597-66vd2mdu 545 10 were be VBD cord-014597-66vd2mdu 545 11 cultured culture VBN cord-014597-66vd2mdu 545 12 in in IN cord-014597-66vd2mdu 545 13 three three CD cord-014597-66vd2mdu 545 14 replicates replicate NNS cord-014597-66vd2mdu 545 15 in in IN cord-014597-66vd2mdu 545 16 shakers shaker NNS cord-014597-66vd2mdu 545 17 . . . cord-014597-66vd2mdu 546 1 Supernatant supernatant JJ cord-014597-66vd2mdu 546 2 from from IN cord-014597-66vd2mdu 546 3 the the DT cord-014597-66vd2mdu 546 4 cultures culture NNS cord-014597-66vd2mdu 546 5 were be VBD cord-014597-66vd2mdu 546 6 harvested harvest VBN cord-014597-66vd2mdu 546 7 at at IN cord-014597-66vd2mdu 546 8 four four CD cord-014597-66vd2mdu 546 9 time time NN cord-014597-66vd2mdu 546 10 points point NNS cord-014597-66vd2mdu 546 11 . . . cord-014597-66vd2mdu 547 1 The the DT cord-014597-66vd2mdu 547 2 removed remove VBN cord-014597-66vd2mdu 547 3 culture culture NN cord-014597-66vd2mdu 547 4 volume volume NN cord-014597-66vd2mdu 547 5 was be VBD cord-014597-66vd2mdu 547 6 replaced replace VBN cord-014597-66vd2mdu 547 7 by by IN cord-014597-66vd2mdu 547 8 culture culture NN cord-014597-66vd2mdu 547 9 supernatant supernatant JJ cord-014597-66vd2mdu 547 10 of of IN cord-014597-66vd2mdu 547 11 the the DT cord-014597-66vd2mdu 547 12 identically identically RB cord-014597-66vd2mdu 547 13 cultured cultured JJ cord-014597-66vd2mdu 547 14 corresponding correspond VBG cord-014597-66vd2mdu 547 15 parental parental JJ cord-014597-66vd2mdu 547 16 cell cell NN cord-014597-66vd2mdu 547 17 line line NN cord-014597-66vd2mdu 547 18 . . . cord-014597-66vd2mdu 548 1 The the DT cord-014597-66vd2mdu 548 2 product product NN cord-014597-66vd2mdu 548 3 was be VBD cord-014597-66vd2mdu 548 4 isolated isolate VBN cord-014597-66vd2mdu 548 5 from from IN cord-014597-66vd2mdu 548 6 the the DT cord-014597-66vd2mdu 548 7 supernatant supernatant NN cord-014597-66vd2mdu 548 8 and and CC cord-014597-66vd2mdu 548 9 the the DT cord-014597-66vd2mdu 548 10 glycans glycan NNS cord-014597-66vd2mdu 548 11 were be VBD cord-014597-66vd2mdu 548 12 released release VBN cord-014597-66vd2mdu 548 13 . . . cord-014597-66vd2mdu 549 1 One one CD cord-014597-66vd2mdu 549 2 part part NN cord-014597-66vd2mdu 549 3 of of IN cord-014597-66vd2mdu 549 4 the the DT cord-014597-66vd2mdu 549 5 released release VBN cord-014597-66vd2mdu 549 6 glycans glycan NNS cord-014597-66vd2mdu 549 7 was be VBD cord-014597-66vd2mdu 549 8 labeled label VBN cord-014597-66vd2mdu 549 9 with with IN cord-014597-66vd2mdu 549 10 2-AB 2-ab CD cord-014597-66vd2mdu 549 11 and and CC cord-014597-66vd2mdu 549 12 separated separate VBN cord-014597-66vd2mdu 549 13 by by IN cord-014597-66vd2mdu 549 14 HILIC HILIC NNP cord-014597-66vd2mdu 549 15 - - HYPH cord-014597-66vd2mdu 549 16 FLD FLD NNP cord-014597-66vd2mdu 549 17 . . . cord-014597-66vd2mdu 550 1 The the DT cord-014597-66vd2mdu 550 2 other other JJ cord-014597-66vd2mdu 550 3 part part NN cord-014597-66vd2mdu 550 4 of of IN cord-014597-66vd2mdu 550 5 the the DT cord-014597-66vd2mdu 550 6 glycans glycan NNS cord-014597-66vd2mdu 550 7 was be VBD cord-014597-66vd2mdu 550 8 permethylated permethylate VBN cord-014597-66vd2mdu 550 9 and and CC cord-014597-66vd2mdu 550 10 analyzed analyze VBN cord-014597-66vd2mdu 550 11 by by IN cord-014597-66vd2mdu 550 12 MALDI MALDI NNP cord-014597-66vd2mdu 550 13 - - HYPH cord-014597-66vd2mdu 550 14 ToF ToF NNP cord-014597-66vd2mdu 550 15 mass mass NN cord-014597-66vd2mdu 550 16 spectrometry spectrometry NN cord-014597-66vd2mdu 550 17 ( ( -LRB- cord-014597-66vd2mdu 550 18 Fig Fig NNP cord-014597-66vd2mdu 550 19 . . . cord-014597-66vd2mdu 550 20 1a 1a CD cord-014597-66vd2mdu 550 21 ) ) -RRB- cord-014597-66vd2mdu 550 22 . . . cord-014597-66vd2mdu 551 1 The the DT cord-014597-66vd2mdu 551 2 investigated investigate VBN cord-014597-66vd2mdu 551 3 proteins protein NNS cord-014597-66vd2mdu 551 4 were be VBD cord-014597-66vd2mdu 551 5 Antibody Antibody NNP cord-014597-66vd2mdu 551 6 , , , cord-014597-66vd2mdu 551 7 Antithrombin Antithrombin NNP cord-014597-66vd2mdu 551 8 III III NNP cord-014597-66vd2mdu 551 9 from from IN cord-014597-66vd2mdu 551 10 CHO CHO NNP cord-014597-66vd2mdu 551 11 clones clone NNS cord-014597-66vd2mdu 551 12 and and CC cord-014597-66vd2mdu 551 13 α1-Antitrypsin α1-Antitrypsin NNP cord-014597-66vd2mdu 551 14 , , , cord-014597-66vd2mdu 551 15 C1-Inhibitor C1-Inhibitor NNP cord-014597-66vd2mdu 551 16 from from IN cord-014597-66vd2mdu 551 17 human human JJ cord-014597-66vd2mdu 551 18 clones clone NNS cord-014597-66vd2mdu 551 19 . . . cord-014597-66vd2mdu 552 1 The the DT cord-014597-66vd2mdu 552 2 antennarity antennarity NN cord-014597-66vd2mdu 552 3 of of IN cord-014597-66vd2mdu 552 4 the the DT cord-014597-66vd2mdu 552 5 glycans glycan NNS cord-014597-66vd2mdu 552 6 is be VBZ cord-014597-66vd2mdu 552 7 quite quite RB cord-014597-66vd2mdu 552 8 stable stable JJ cord-014597-66vd2mdu 552 9 in in IN cord-014597-66vd2mdu 552 10 all all DT cord-014597-66vd2mdu 552 11 production production NN cord-014597-66vd2mdu 552 12 phases phase NNS cord-014597-66vd2mdu 552 13 . . . cord-014597-66vd2mdu 553 1 The the DT cord-014597-66vd2mdu 553 2 degree degree NN cord-014597-66vd2mdu 553 3 of of IN cord-014597-66vd2mdu 553 4 core core NN cord-014597-66vd2mdu 553 5 fucosylation fucosylation NN cord-014597-66vd2mdu 553 6 is be VBZ cord-014597-66vd2mdu 553 7 very very RB cord-014597-66vd2mdu 553 8 high high JJ cord-014597-66vd2mdu 553 9 in in IN cord-014597-66vd2mdu 553 10 all all DT cord-014597-66vd2mdu 553 11 products product NNS cord-014597-66vd2mdu 553 12 . . . cord-014597-66vd2mdu 554 1 A a DT cord-014597-66vd2mdu 554 2 low low JJ cord-014597-66vd2mdu 554 3 fucosylation fucosylation NN cord-014597-66vd2mdu 554 4 degree degree NN cord-014597-66vd2mdu 554 5 of of IN cord-014597-66vd2mdu 554 6 antibodies antibody NNS cord-014597-66vd2mdu 554 7 may may MD cord-014597-66vd2mdu 554 8 be be VB cord-014597-66vd2mdu 554 9 favorable favorable JJ cord-014597-66vd2mdu 554 10 for for IN cord-014597-66vd2mdu 554 11 a a DT cord-014597-66vd2mdu 554 12 higher high JJR cord-014597-66vd2mdu 554 13 ADCC ADCC NNP cord-014597-66vd2mdu 554 14 performance performance NN cord-014597-66vd2mdu 554 15 [ [ -LRB- cord-014597-66vd2mdu 554 16 2 2 CD cord-014597-66vd2mdu 554 17 ] ] -RRB- cord-014597-66vd2mdu 554 18 . . . cord-014597-66vd2mdu 555 1 Some some DT cord-014597-66vd2mdu 555 2 of of IN cord-014597-66vd2mdu 555 3 the the DT cord-014597-66vd2mdu 555 4 products product NNS cord-014597-66vd2mdu 555 5 showed show VBD cord-014597-66vd2mdu 555 6 an an DT cord-014597-66vd2mdu 555 7 antennary antennary JJ cord-014597-66vd2mdu 555 8 fucosylation fucosylation NN cord-014597-66vd2mdu 555 9 , , , cord-014597-66vd2mdu 555 10 which which WDT cord-014597-66vd2mdu 555 11 seemed seem VBD cord-014597-66vd2mdu 555 12 to to TO cord-014597-66vd2mdu 555 13 change change VB cord-014597-66vd2mdu 555 14 not not RB cord-014597-66vd2mdu 555 15 very very RB cord-014597-66vd2mdu 555 16 much much RB cord-014597-66vd2mdu 555 17 in in IN cord-014597-66vd2mdu 555 18 different different JJ cord-014597-66vd2mdu 555 19 cultivation cultivation NN cord-014597-66vd2mdu 555 20 phases phase NNS cord-014597-66vd2mdu 555 21 . . . cord-014597-66vd2mdu 556 1 Nevertheless nevertheless RB cord-014597-66vd2mdu 556 2 , , , cord-014597-66vd2mdu 556 3 this this DT cord-014597-66vd2mdu 556 4 might may MD cord-014597-66vd2mdu 556 5 be be VB cord-014597-66vd2mdu 556 6 an an DT cord-014597-66vd2mdu 556 7 issue issue NN cord-014597-66vd2mdu 556 8 due due IN cord-014597-66vd2mdu 556 9 to to IN cord-014597-66vd2mdu 556 10 an an DT cord-014597-66vd2mdu 556 11 antigenic antigenic JJ cord-014597-66vd2mdu 556 12 impact impact NN cord-014597-66vd2mdu 556 13 in in IN cord-014597-66vd2mdu 556 14 the the DT cord-014597-66vd2mdu 556 15 patient patient NN cord-014597-66vd2mdu 556 16 . . . cord-014597-66vd2mdu 557 1 The the DT cord-014597-66vd2mdu 557 2 antennary antennary JJ cord-014597-66vd2mdu 557 3 galactosylation galactosylation NN cord-014597-66vd2mdu 557 4 changes change VBZ cord-014597-66vd2mdu 557 5 noticeable noticeable JJ cord-014597-66vd2mdu 557 6 for for IN cord-014597-66vd2mdu 557 7 the the DT cord-014597-66vd2mdu 557 8 antibody antibody NN cord-014597-66vd2mdu 557 9 and and CC cord-014597-66vd2mdu 557 10 α1-Antitrypsin α1-Antitrypsin NNP cord-014597-66vd2mdu 557 11 . . . cord-014597-66vd2mdu 558 1 In in IN cord-014597-66vd2mdu 558 2 both both DT cord-014597-66vd2mdu 558 3 cases case NNS cord-014597-66vd2mdu 558 4 the the DT cord-014597-66vd2mdu 558 5 degree degree NN cord-014597-66vd2mdu 558 6 is be VBZ cord-014597-66vd2mdu 558 7 highest high JJS cord-014597-66vd2mdu 558 8 in in IN cord-014597-66vd2mdu 558 9 the the DT cord-014597-66vd2mdu 558 10 first first JJ cord-014597-66vd2mdu 558 11 phase phase NN cord-014597-66vd2mdu 558 12 . . . cord-014597-66vd2mdu 559 1 An an DT cord-014597-66vd2mdu 559 2 incomplete incomplete JJ cord-014597-66vd2mdu 559 3 galactosylation galactosylation NN cord-014597-66vd2mdu 559 4 leads lead VBZ cord-014597-66vd2mdu 559 5 to to IN cord-014597-66vd2mdu 559 6 truncated truncated JJ cord-014597-66vd2mdu 559 7 glycans glycan NNS cord-014597-66vd2mdu 559 8 . . . cord-014597-66vd2mdu 560 1 This this DT cord-014597-66vd2mdu 560 2 leads lead VBZ cord-014597-66vd2mdu 560 3 inevitable inevitable JJ cord-014597-66vd2mdu 560 4 to to IN cord-014597-66vd2mdu 560 5 undersialylated undersialylated JJ cord-014597-66vd2mdu 560 6 antennas antenna NNS cord-014597-66vd2mdu 560 7 to to TO cord-014597-66vd2mdu 560 8 be be VB cord-014597-66vd2mdu 560 9 seen see VBN cord-014597-66vd2mdu 560 10 for for IN cord-014597-66vd2mdu 560 11 α1-Antitrypsin α1-Antitrypsin NNP cord-014597-66vd2mdu 560 12 . . . cord-014597-66vd2mdu 561 1 The the DT cord-014597-66vd2mdu 561 2 sialylation sialylation NN cord-014597-66vd2mdu 561 3 is be VBZ cord-014597-66vd2mdu 561 4 the the DT cord-014597-66vd2mdu 561 5 highest high JJS cord-014597-66vd2mdu 561 6 in in IN cord-014597-66vd2mdu 561 7 the the DT cord-014597-66vd2mdu 561 8 early early JJ cord-014597-66vd2mdu 561 9 phases phase NNS cord-014597-66vd2mdu 561 10 and and CC cord-014597-66vd2mdu 561 11 decreases decrease NNS cord-014597-66vd2mdu 561 12 during during IN cord-014597-66vd2mdu 561 13 cultivation cultivation NN cord-014597-66vd2mdu 561 14 time time NN cord-014597-66vd2mdu 561 15 . . . cord-014597-66vd2mdu 562 1 Sialylation sialylation NN cord-014597-66vd2mdu 562 2 of of IN cord-014597-66vd2mdu 562 3 a a DT cord-014597-66vd2mdu 562 4 therapeutical therapeutical JJ cord-014597-66vd2mdu 562 5 protein protein NN cord-014597-66vd2mdu 562 6 is be VBZ cord-014597-66vd2mdu 562 7 important important JJ cord-014597-66vd2mdu 562 8 for for IN cord-014597-66vd2mdu 562 9 the the DT cord-014597-66vd2mdu 562 10 half half JJ cord-014597-66vd2mdu 562 11 - - HYPH cord-014597-66vd2mdu 562 12 life life NN cord-014597-66vd2mdu 562 13 in in IN cord-014597-66vd2mdu 562 14 the the DT cord-014597-66vd2mdu 562 15 patient patient NN cord-014597-66vd2mdu 562 16 . . . cord-014597-66vd2mdu 563 1 Therefore therefore RB cord-014597-66vd2mdu 563 2 highly highly RB cord-014597-66vd2mdu 563 3 sialylated sialylate VBN cord-014597-66vd2mdu 563 4 products product NNS cord-014597-66vd2mdu 563 5 are be VBP cord-014597-66vd2mdu 563 6 desired desire VBN cord-014597-66vd2mdu 563 7 [ [ -LRB- cord-014597-66vd2mdu 563 8 3 3 CD cord-014597-66vd2mdu 563 9 ] ] -RRB- cord-014597-66vd2mdu 563 10 . . . cord-014597-66vd2mdu 564 1 In in IN cord-014597-66vd2mdu 564 2 further further JJ cord-014597-66vd2mdu 564 3 studies study NNS cord-014597-66vd2mdu 564 4 the the DT cord-014597-66vd2mdu 564 5 consistency consistency NN cord-014597-66vd2mdu 564 6 of of IN cord-014597-66vd2mdu 564 7 the the DT cord-014597-66vd2mdu 564 8 galactosylation galactosylation NN cord-014597-66vd2mdu 564 9 and and CC cord-014597-66vd2mdu 564 10 the the DT cord-014597-66vd2mdu 564 11 sialylation sialylation NN cord-014597-66vd2mdu 564 12 will will MD cord-014597-66vd2mdu 564 13 investigated investigate VBN cord-014597-66vd2mdu 564 14 for for IN cord-014597-66vd2mdu 564 15 fed fed NNP cord-014597-66vd2mdu 564 16 batch batch NN cord-014597-66vd2mdu 564 17 and and CC cord-014597-66vd2mdu 564 18 long long JJ cord-014597-66vd2mdu 564 19 term term NN cord-014597-66vd2mdu 564 20 continuous continuous JJ cord-014597-66vd2mdu 564 21 cultures culture NNS cord-014597-66vd2mdu 564 22 in in IN cord-014597-66vd2mdu 564 23 comparison comparison NN cord-014597-66vd2mdu 564 24 to to TO cord-014597-66vd2mdu 564 25 batch batch VB cord-014597-66vd2mdu 564 26 cultures culture NNS cord-014597-66vd2mdu 564 27 . . . cord-014597-66vd2mdu 565 1 Due due IN cord-014597-66vd2mdu 565 2 to to IN cord-014597-66vd2mdu 565 3 the the DT cord-014597-66vd2mdu 565 4 feed feed NN cord-014597-66vd2mdu 565 5 solution solution NN cord-014597-66vd2mdu 565 6 or or CC cord-014597-66vd2mdu 565 7 the the DT cord-014597-66vd2mdu 565 8 fresh fresh JJ cord-014597-66vd2mdu 565 9 media medium NNS cord-014597-66vd2mdu 565 10 being be VBG cord-014597-66vd2mdu 565 11 present present JJ cord-014597-66vd2mdu 565 12 during during IN cord-014597-66vd2mdu 565 13 such such JJ cord-014597-66vd2mdu 565 14 processes process NNS cord-014597-66vd2mdu 565 15 , , , cord-014597-66vd2mdu 565 16 the the DT cord-014597-66vd2mdu 565 17 supply supply NN cord-014597-66vd2mdu 565 18 situation situation NN cord-014597-66vd2mdu 565 19 should should MD cord-014597-66vd2mdu 565 20 be be VB cord-014597-66vd2mdu 565 21 excellent excellent JJ cord-014597-66vd2mdu 565 22 for for IN cord-014597-66vd2mdu 565 23 the the DT cord-014597-66vd2mdu 565 24 whole whole JJ cord-014597-66vd2mdu 565 25 cultivation cultivation NN cord-014597-66vd2mdu 565 26 time time NN cord-014597-66vd2mdu 565 27 . . . cord-014597-66vd2mdu 566 1 The the DT cord-014597-66vd2mdu 566 2 differences difference NNS cord-014597-66vd2mdu 566 3 between between IN cord-014597-66vd2mdu 566 4 the the DT cord-014597-66vd2mdu 566 5 MALDI MALDI NNP cord-014597-66vd2mdu 566 6 - - HYPH cord-014597-66vd2mdu 566 7 ToF ToF NNP cord-014597-66vd2mdu 566 8 and and CC cord-014597-66vd2mdu 566 9 HILIC HILIC NNP cord-014597-66vd2mdu 566 10 - - HYPH cord-014597-66vd2mdu 566 11 FLD FLD NNP cord-014597-66vd2mdu 566 12 data datum NNS cord-014597-66vd2mdu 566 13 originate originate VBP cord-014597-66vd2mdu 566 14 from from IN cord-014597-66vd2mdu 566 15 complex complex JJ cord-014597-66vd2mdu 566 16 and and CC cord-014597-66vd2mdu 566 17 unresolved unresolved JJ cord-014597-66vd2mdu 566 18 chromatograms chromatogram NNS cord-014597-66vd2mdu 566 19 ( ( -LRB- cord-014597-66vd2mdu 566 20 Fig Fig NNP cord-014597-66vd2mdu 566 21 . . . cord-014597-66vd2mdu 567 1 1b 1b NNP cord-014597-66vd2mdu 567 2 , , , cord-014597-66vd2mdu 567 3 chromatograms chromatograms NNP cord-014597-66vd2mdu 567 4 not not RB cord-014597-66vd2mdu 567 5 shown show VBN cord-014597-66vd2mdu 567 6 ) ) -RRB- cord-014597-66vd2mdu 567 7 . . . cord-014597-66vd2mdu 568 1 For for IN cord-014597-66vd2mdu 568 2 that that DT cord-014597-66vd2mdu 568 3 reason reason NN cord-014597-66vd2mdu 568 4 coupling coupling NN cord-014597-66vd2mdu 568 5 of of IN cord-014597-66vd2mdu 568 6 HILIC HILIC NNP cord-014597-66vd2mdu 568 7 - - HYPH cord-014597-66vd2mdu 568 8 FLD FLD NNP cord-014597-66vd2mdu 568 9 and and CC cord-014597-66vd2mdu 568 10 MS MS NNP cord-014597-66vd2mdu 568 11 is be VBZ cord-014597-66vd2mdu 568 12 very very RB cord-014597-66vd2mdu 568 13 much much RB cord-014597-66vd2mdu 568 14 recommended recommend VBN cord-014597-66vd2mdu 568 15 . . . cord-014597-66vd2mdu 569 1 Background Background NNP cord-014597-66vd2mdu 569 2 Novel Novel NNP cord-014597-66vd2mdu 569 3 biologics biologic NNS cord-014597-66vd2mdu 569 4 are be VBP cord-014597-66vd2mdu 569 5 often often RB cord-014597-66vd2mdu 569 6 selected select VBN cord-014597-66vd2mdu 569 7 from from IN cord-014597-66vd2mdu 569 8 a a DT cord-014597-66vd2mdu 569 9 large large JJ cord-014597-66vd2mdu 569 10 library library NN cord-014597-66vd2mdu 569 11 of of IN cord-014597-66vd2mdu 569 12 lead lead JJ cord-014597-66vd2mdu 569 13 candidates candidate NNS cord-014597-66vd2mdu 569 14 in in IN cord-014597-66vd2mdu 569 15 the the DT cord-014597-66vd2mdu 569 16 initial initial JJ cord-014597-66vd2mdu 569 17 stage stage NN cord-014597-66vd2mdu 569 18 of of IN cord-014597-66vd2mdu 569 19 preclinical preclinical JJ cord-014597-66vd2mdu 569 20 and and CC cord-014597-66vd2mdu 569 21 clinical clinical JJ cord-014597-66vd2mdu 569 22 developments development NNS cord-014597-66vd2mdu 569 23 . . . cord-014597-66vd2mdu 570 1 For for IN cord-014597-66vd2mdu 570 2 this this DT cord-014597-66vd2mdu 570 3 selection selection NN cord-014597-66vd2mdu 570 4 , , , cord-014597-66vd2mdu 570 5 there there EX cord-014597-66vd2mdu 570 6 is be VBZ cord-014597-66vd2mdu 570 7 a a DT cord-014597-66vd2mdu 570 8 demand demand NN cord-014597-66vd2mdu 570 9 for for IN cord-014597-66vd2mdu 570 10 high high JJ cord-014597-66vd2mdu 570 11 - - HYPH cord-014597-66vd2mdu 570 12 throughput throughput NN cord-014597-66vd2mdu 570 13 production production NN cord-014597-66vd2mdu 570 14 of of IN cord-014597-66vd2mdu 570 15 recombinant recombinant JJ cord-014597-66vd2mdu 570 16 proteins protein NNS cord-014597-66vd2mdu 570 17 of of IN cord-014597-66vd2mdu 570 18 high high JJ cord-014597-66vd2mdu 570 19 quality quality NN cord-014597-66vd2mdu 570 20 and and CC cord-014597-66vd2mdu 570 21 in in IN cord-014597-66vd2mdu 570 22 sufficient sufficient JJ cord-014597-66vd2mdu 570 23 quantity quantity NN cord-014597-66vd2mdu 570 24 . . . cord-014597-66vd2mdu 571 1 Transient transient JJ cord-014597-66vd2mdu 571 2 gene gene NN cord-014597-66vd2mdu 571 3 expression expression NN cord-014597-66vd2mdu 571 4 offers offer VBZ cord-014597-66vd2mdu 571 5 a a DT cord-014597-66vd2mdu 571 6 rapid rapid JJ cord-014597-66vd2mdu 571 7 approach approach NN cord-014597-66vd2mdu 571 8 to to IN cord-014597-66vd2mdu 571 9 the the DT cord-014597-66vd2mdu 571 10 production production NN cord-014597-66vd2mdu 571 11 of of IN cord-014597-66vd2mdu 571 12 numerous numerous JJ cord-014597-66vd2mdu 571 13 recombinant recombinant JJ cord-014597-66vd2mdu 571 14 proteins protein NNS cord-014597-66vd2mdu 571 15 for for IN cord-014597-66vd2mdu 571 16 the the DT cord-014597-66vd2mdu 571 17 initial initial JJ cord-014597-66vd2mdu 571 18 - - HYPH cord-014597-66vd2mdu 571 19 stage stage NN cord-014597-66vd2mdu 571 20 developments development NNS cord-014597-66vd2mdu 571 21 of of IN cord-014597-66vd2mdu 571 22 biologics biologic NNS cord-014597-66vd2mdu 571 23 . . . cord-014597-66vd2mdu 572 1 Mammalian mammalian JJ cord-014597-66vd2mdu 572 2 cells cell NNS cord-014597-66vd2mdu 572 3 are be VBP cord-014597-66vd2mdu 572 4 major major JJ cord-014597-66vd2mdu 572 5 host host NN cord-014597-66vd2mdu 572 6 cells cell NNS cord-014597-66vd2mdu 572 7 for for IN cord-014597-66vd2mdu 572 8 transient transient JJ cord-014597-66vd2mdu 572 9 gene gene NN cord-014597-66vd2mdu 572 10 expression expression NN cord-014597-66vd2mdu 572 11 , , , cord-014597-66vd2mdu 572 12 but but CC cord-014597-66vd2mdu 572 13 they -PRON- PRP cord-014597-66vd2mdu 572 14 have have VBP cord-014597-66vd2mdu 572 15 the the DT cord-014597-66vd2mdu 572 16 disadvantages disadvantage NNS cord-014597-66vd2mdu 572 17 of of IN cord-014597-66vd2mdu 572 18 complicated complicated JJ cord-014597-66vd2mdu 572 19 operations operation NNS cord-014597-66vd2mdu 572 20 and and CC cord-014597-66vd2mdu 572 21 high high JJ cord-014597-66vd2mdu 572 22 cost cost NN cord-014597-66vd2mdu 572 23 of of IN cord-014597-66vd2mdu 572 24 culture culture NN cord-014597-66vd2mdu 572 25 . . . cord-014597-66vd2mdu 573 1 Insect insect NN cord-014597-66vd2mdu 573 2 cells cell NNS cord-014597-66vd2mdu 573 3 are be VBP cord-014597-66vd2mdu 573 4 easy easy JJ cord-014597-66vd2mdu 573 5 to to TO cord-014597-66vd2mdu 573 6 handle handle VB cord-014597-66vd2mdu 573 7 and and CC cord-014597-66vd2mdu 573 8 can can MD cord-014597-66vd2mdu 573 9 be be VB cord-014597-66vd2mdu 573 10 grown grow VBN cord-014597-66vd2mdu 573 11 to to IN cord-014597-66vd2mdu 573 12 a a DT cord-014597-66vd2mdu 573 13 high high JJ cord-014597-66vd2mdu 573 14 cell cell NN cord-014597-66vd2mdu 573 15 density density NN cord-014597-66vd2mdu 573 16 in in IN cord-014597-66vd2mdu 573 17 suspension suspension NN cord-014597-66vd2mdu 573 18 with with IN cord-014597-66vd2mdu 573 19 a a DT cord-014597-66vd2mdu 573 20 serum serum NN cord-014597-66vd2mdu 573 21 - - HYPH cord-014597-66vd2mdu 573 22 free free JJ cord-014597-66vd2mdu 573 23 medium medium NN cord-014597-66vd2mdu 573 24 . . . cord-014597-66vd2mdu 574 1 Insect insect NN cord-014597-66vd2mdu 574 2 cells cell NNS cord-014597-66vd2mdu 574 3 can can MD cord-014597-66vd2mdu 574 4 also also RB cord-014597-66vd2mdu 574 5 produce produce VB cord-014597-66vd2mdu 574 6 large large JJ cord-014597-66vd2mdu 574 7 amount amount NN cord-014597-66vd2mdu 574 8 of of IN cord-014597-66vd2mdu 574 9 recombinant recombinant JJ cord-014597-66vd2mdu 574 10 proteins protein NNS cord-014597-66vd2mdu 574 11 through through IN cord-014597-66vd2mdu 574 12 post post JJ cord-014597-66vd2mdu 574 13 - - JJ cord-014597-66vd2mdu 574 14 translational translational JJ cord-014597-66vd2mdu 574 15 processing processing NN cord-014597-66vd2mdu 574 16 and and CC cord-014597-66vd2mdu 574 17 modifications modification NNS cord-014597-66vd2mdu 574 18 of of IN cord-014597-66vd2mdu 574 19 higher high JJR cord-014597-66vd2mdu 574 20 eukaryotes eukaryote NNS cord-014597-66vd2mdu 574 21 . . . cord-014597-66vd2mdu 575 1 Hence hence RB cord-014597-66vd2mdu 575 2 , , , cord-014597-66vd2mdu 575 3 insect insect NN cord-014597-66vd2mdu 575 4 cells cell NNS cord-014597-66vd2mdu 575 5 have have VBP cord-014597-66vd2mdu 575 6 been be VBN cord-014597-66vd2mdu 575 7 recognized recognize VBN cord-014597-66vd2mdu 575 8 as as IN cord-014597-66vd2mdu 575 9 an an DT cord-014597-66vd2mdu 575 10 excellent excellent JJ cord-014597-66vd2mdu 575 11 platform platform NN cord-014597-66vd2mdu 575 12 for for IN cord-014597-66vd2mdu 575 13 the the DT cord-014597-66vd2mdu 575 14 production production NN cord-014597-66vd2mdu 575 15 of of IN cord-014597-66vd2mdu 575 16 functional functional JJ cord-014597-66vd2mdu 575 17 recombinant recombinant JJ cord-014597-66vd2mdu 575 18 proteins protein NNS cord-014597-66vd2mdu 575 19 [ [ -LRB- cord-014597-66vd2mdu 575 20 1 1 CD cord-014597-66vd2mdu 575 21 , , , cord-014597-66vd2mdu 575 22 2 2 CD cord-014597-66vd2mdu 575 23 ] ] -RRB- cord-014597-66vd2mdu 575 24 . . . cord-014597-66vd2mdu 576 1 In in IN cord-014597-66vd2mdu 576 2 the the DT cord-014597-66vd2mdu 576 3 present present JJ cord-014597-66vd2mdu 576 4 study study NN cord-014597-66vd2mdu 576 5 , , , cord-014597-66vd2mdu 576 6 the the DT cord-014597-66vd2mdu 576 7 production production NN cord-014597-66vd2mdu 576 8 of of IN cord-014597-66vd2mdu 576 9 an an DT cord-014597-66vd2mdu 576 10 antibody antibody NN cord-014597-66vd2mdu 576 11 Fab Fab NNP cord-014597-66vd2mdu 576 12 fragment fragment NN cord-014597-66vd2mdu 576 13 through through IN cord-014597-66vd2mdu 576 14 transient transient JJ cord-014597-66vd2mdu 576 15 gene gene NN cord-014597-66vd2mdu 576 16 expression expression NN cord-014597-66vd2mdu 576 17 in in IN cord-014597-66vd2mdu 576 18 lepidopteran lepidopteran JJ cord-014597-66vd2mdu 576 19 insect insect NN cord-014597-66vd2mdu 576 20 cells cell NNS cord-014597-66vd2mdu 576 21 was be VBD cord-014597-66vd2mdu 576 22 examined examine VBN cord-014597-66vd2mdu 576 23 . . . cord-014597-66vd2mdu 577 1 The the DT cord-014597-66vd2mdu 577 2 DNA dna NN cord-014597-66vd2mdu 577 3 fragments fragment NNS cord-014597-66vd2mdu 577 4 encoding encode VBG cord-014597-66vd2mdu 577 5 the the DT cord-014597-66vd2mdu 577 6 heavy heavy JJ cord-014597-66vd2mdu 577 7 chain chain NN cord-014597-66vd2mdu 577 8 ( ( -LRB- cord-014597-66vd2mdu 577 9 Hc Hc NNP cord-014597-66vd2mdu 577 10 ) ) -RRB- cord-014597-66vd2mdu 577 11 and and CC cord-014597-66vd2mdu 578 1 light light JJ cord-014597-66vd2mdu 578 2 chain chain NN cord-014597-66vd2mdu 578 3 ( ( -LRB- cord-014597-66vd2mdu 578 4 Lc Lc NNP cord-014597-66vd2mdu 578 5 ) ) -RRB- cord-014597-66vd2mdu 578 6 genes gene NNS cord-014597-66vd2mdu 578 7 of of IN cord-014597-66vd2mdu 578 8 an an DT cord-014597-66vd2mdu 578 9 Fab Fab NNP cord-014597-66vd2mdu 578 10 fragment fragment NN cord-014597-66vd2mdu 578 11 of of IN cord-014597-66vd2mdu 578 12 mouse mouse NN cord-014597-66vd2mdu 578 13 anti anti JJ cord-014597-66vd2mdu 578 14 - - JJ cord-014597-66vd2mdu 578 15 bovine bovine JJ cord-014597-66vd2mdu 578 16 RNaseA rnasea NN cord-014597-66vd2mdu 578 17 [ [ -LRB- cord-014597-66vd2mdu 578 18 3 3 CD cord-014597-66vd2mdu 578 19 ] ] -RRB- cord-014597-66vd2mdu 578 20 were be VBD cord-014597-66vd2mdu 578 21 respectively respectively RB cord-014597-66vd2mdu 578 22 cloned clone VBN cord-014597-66vd2mdu 578 23 into into IN cord-014597-66vd2mdu 578 24 the the DT cord-014597-66vd2mdu 578 25 plasmid plasmid NN cord-014597-66vd2mdu 578 26 vector vector NN cord-014597-66vd2mdu 578 27 pIHAneo pIHAneo NNP cord-014597-66vd2mdu 578 28 , , , cord-014597-66vd2mdu 578 29 which which WDT cord-014597-66vd2mdu 578 30 contained contain VBD cord-014597-66vd2mdu 578 31 the the DT cord-014597-66vd2mdu 578 32 Bombyx Bombyx NNP cord-014597-66vd2mdu 578 33 mori mori NN cord-014597-66vd2mdu 578 34 actin actin NN cord-014597-66vd2mdu 578 35 promoter promoter NN cord-014597-66vd2mdu 578 36 downstream downstream RB cord-014597-66vd2mdu 578 37 of of IN cord-014597-66vd2mdu 578 38 the the DT cord-014597-66vd2mdu 578 39 B. B. NNP cord-014597-66vd2mdu 578 40 mori mori NNP cord-014597-66vd2mdu 578 41 nucleopolyhedrovirus nucleopolyhedrovirus NNP cord-014597-66vd2mdu 578 42 ( ( -LRB- cord-014597-66vd2mdu 578 43 BmNPV BmNPV NNP cord-014597-66vd2mdu 578 44 ) ) -RRB- cord-014597-66vd2mdu 579 1 IE-1 IE-1 NNP cord-014597-66vd2mdu 580 1 transactivator transactivator NNP cord-014597-66vd2mdu 580 2 and and CC cord-014597-66vd2mdu 580 3 the the DT cord-014597-66vd2mdu 580 4 BmNPV BmNPV NNP cord-014597-66vd2mdu 580 5 HR3 HR3 NNP cord-014597-66vd2mdu 580 6 enhancer enhancer NN cord-014597-66vd2mdu 580 7 for for IN cord-014597-66vd2mdu 580 8 high high JJ cord-014597-66vd2mdu 580 9 - - HYPH cord-014597-66vd2mdu 580 10 level level NN cord-014597-66vd2mdu 580 11 expression expression NN cord-014597-66vd2mdu 580 12 [ [ -LRB- cord-014597-66vd2mdu 580 13 4 4 CD cord-014597-66vd2mdu 580 14 ] ] -RRB- cord-014597-66vd2mdu 580 15 . . . cord-014597-66vd2mdu 581 1 Trichoplusia Trichoplusia NNP cord-014597-66vd2mdu 581 2 ni ni NNP cord-014597-66vd2mdu 582 1 BTI BTI NNP cord-014597-66vd2mdu 582 2 - - HYPH cord-014597-66vd2mdu 582 3 TN-5B1 TN-5B1 NNP cord-014597-66vd2mdu 582 4 - - HYPH cord-014597-66vd2mdu 582 5 4 4 CD cord-014597-66vd2mdu 583 1 ( ( -LRB- cord-014597-66vd2mdu 583 2 High High NNP cord-014597-66vd2mdu 583 3 Five five CD cord-014597-66vd2mdu 583 4 ) ) -RRB- cord-014597-66vd2mdu 583 5 cells cell NNS cord-014597-66vd2mdu 583 6 were be VBD cord-014597-66vd2mdu 583 7 co co JJ cord-014597-66vd2mdu 583 8 - - VBN cord-014597-66vd2mdu 583 9 transfected transfecte VBN cord-014597-66vd2mdu 583 10 with with IN cord-014597-66vd2mdu 583 11 the the DT cord-014597-66vd2mdu 583 12 resultant resultant JJ cord-014597-66vd2mdu 583 13 plasmid plasmid NN cord-014597-66vd2mdu 583 14 vectors vector NNS cord-014597-66vd2mdu 583 15 using use VBG cord-014597-66vd2mdu 583 16 linear linear JJ cord-014597-66vd2mdu 583 17 polyethyleneimine polyethyleneimine NNP cord-014597-66vd2mdu 583 18 ( ( -LRB- cord-014597-66vd2mdu 583 19 PEI PEI NNP cord-014597-66vd2mdu 583 20 ; ; : cord-014597-66vd2mdu 583 21 Mw Mw NNP cord-014597-66vd2mdu 583 22 40,000 40,000 CD cord-014597-66vd2mdu 583 23 ) ) -RRB- cord-014597-66vd2mdu 583 24 . . . cord-014597-66vd2mdu 584 1 Before before IN cord-014597-66vd2mdu 584 2 transfection transfection NN cord-014597-66vd2mdu 584 3 , , , cord-014597-66vd2mdu 584 4 the the DT cord-014597-66vd2mdu 584 5 plasmids plasmid NNS cord-014597-66vd2mdu 584 6 and and CC cord-014597-66vd2mdu 584 7 PEI PEI NNP cord-014597-66vd2mdu 584 8 were be VBD cord-014597-66vd2mdu 584 9 prepared prepare VBN cord-014597-66vd2mdu 584 10 in in IN cord-014597-66vd2mdu 584 11 150 150 CD cord-014597-66vd2mdu 584 12 mM mm CD cord-014597-66vd2mdu 584 13 NaCl nacl NN cord-014597-66vd2mdu 584 14 , , , cord-014597-66vd2mdu 584 15 pH pH NNP cord-014597-66vd2mdu 584 16 7.0 7.0 CD cord-014597-66vd2mdu 584 17 and and CC cord-014597-66vd2mdu 584 18 incubated incubate VBN cord-014597-66vd2mdu 584 19 at at IN cord-014597-66vd2mdu 584 20 room room NN cord-014597-66vd2mdu 584 21 temperature temperature NN cord-014597-66vd2mdu 584 22 for for IN cord-014597-66vd2mdu 584 23 5 5 CD cord-014597-66vd2mdu 584 24 min min NN cord-014597-66vd2mdu 584 25 . . . cord-014597-66vd2mdu 585 1 When when WRB cord-014597-66vd2mdu 585 2 the the DT cord-014597-66vd2mdu 585 3 transfection transfection NN cord-014597-66vd2mdu 585 4 efficiency efficiency NN cord-014597-66vd2mdu 585 5 was be VBD cord-014597-66vd2mdu 585 6 checked check VBN cord-014597-66vd2mdu 585 7 , , , cord-014597-66vd2mdu 585 8 a a DT cord-014597-66vd2mdu 585 9 plasmid plasmid NN cord-014597-66vd2mdu 585 10 vector vector NN cord-014597-66vd2mdu 585 11 encoding encoding NN cord-014597-66vd2mdu 586 1 the the DT cord-014597-66vd2mdu 586 2 enhanced enhanced JJ cord-014597-66vd2mdu 586 3 green green JJ cord-014597-66vd2mdu 586 4 fluorescent fluorescent NN cord-014597-66vd2mdu 586 5 protein protein NN cord-014597-66vd2mdu 586 6 ( ( -LRB- cord-014597-66vd2mdu 586 7 EGFP EGFP NNP cord-014597-66vd2mdu 586 8 ) ) -RRB- cord-014597-66vd2mdu 586 9 gene gene NN cord-014597-66vd2mdu 586 10 was be VBD cord-014597-66vd2mdu 586 11 also also RB cord-014597-66vd2mdu 586 12 co co VBN cord-014597-66vd2mdu 586 13 - - VBN cord-014597-66vd2mdu 586 14 transfected transfecte VBN cord-014597-66vd2mdu 586 15 . . . cord-014597-66vd2mdu 587 1 Transfected transfected JJ cord-014597-66vd2mdu 587 2 cells cell NNS cord-014597-66vd2mdu 587 3 were be VBD cord-014597-66vd2mdu 587 4 incubated incubate VBN cord-014597-66vd2mdu 587 5 with with IN cord-014597-66vd2mdu 587 6 a a DT cord-014597-66vd2mdu 587 7 serum serum NN cord-014597-66vd2mdu 587 8 - - HYPH cord-014597-66vd2mdu 587 9 free free JJ cord-014597-66vd2mdu 587 10 medium medium NN cord-014597-66vd2mdu 587 11 in in IN cord-014597-66vd2mdu 587 12 a a DT cord-014597-66vd2mdu 587 13 static static JJ cord-014597-66vd2mdu 587 14 or or CC cord-014597-66vd2mdu 587 15 shake shake NN cord-014597-66vd2mdu 587 16 - - HYPH cord-014597-66vd2mdu 587 17 flask flask NN cord-014597-66vd2mdu 587 18 culture culture NN cord-014597-66vd2mdu 587 19 . . . cord-014597-66vd2mdu 588 1 Culture culture NN cord-014597-66vd2mdu 588 2 supernatants supernatant NNS cord-014597-66vd2mdu 588 3 were be VBD cord-014597-66vd2mdu 588 4 analysed analyse VBN cord-014597-66vd2mdu 588 5 by by IN cord-014597-66vd2mdu 588 6 western western JJ cord-014597-66vd2mdu 588 7 blotting blotting NN cord-014597-66vd2mdu 588 8 and and CC cord-014597-66vd2mdu 588 9 enzyme enzyme NN cord-014597-66vd2mdu 588 10 - - HYPH cord-014597-66vd2mdu 588 11 linked link VBN cord-014597-66vd2mdu 588 12 immunosorbent immunosorbent JJ cord-014597-66vd2mdu 588 13 assay assay NN cord-014597-66vd2mdu 588 14 ( ( -LRB- cord-014597-66vd2mdu 588 15 ELISA ELISA NNP cord-014597-66vd2mdu 588 16 ) ) -RRB- cord-014597-66vd2mdu 588 17 . . . cord-014597-66vd2mdu 589 1 The the DT cord-014597-66vd2mdu 589 2 numbers number NNS cord-014597-66vd2mdu 589 3 of of IN cord-014597-66vd2mdu 589 4 green green JJ cord-014597-66vd2mdu 589 5 fluorescent fluorescent NN cord-014597-66vd2mdu 589 6 cells cell NNS cord-014597-66vd2mdu 589 7 and and CC cord-014597-66vd2mdu 589 8 total total JJ cord-014597-66vd2mdu 589 9 cells cell NNS cord-014597-66vd2mdu 589 10 in in IN cord-014597-66vd2mdu 589 11 culture culture NN cord-014597-66vd2mdu 589 12 broth broth NN cord-014597-66vd2mdu 589 13 was be VBD cord-014597-66vd2mdu 589 14 determined determine VBN cord-014597-66vd2mdu 589 15 using use VBG cord-014597-66vd2mdu 589 16 a a DT cord-014597-66vd2mdu 589 17 flow flow NN cord-014597-66vd2mdu 589 18 cytometer cytometer NN cord-014597-66vd2mdu 589 19 . . . cord-014597-66vd2mdu 590 1 Western western JJ cord-014597-66vd2mdu 590 2 blot blot NN cord-014597-66vd2mdu 590 3 analysis analysis NN cord-014597-66vd2mdu 590 4 and and CC cord-014597-66vd2mdu 590 5 ELISA ELISA NNP cord-014597-66vd2mdu 590 6 of of IN cord-014597-66vd2mdu 590 7 culture culture NN cord-014597-66vd2mdu 590 8 supernatants supernatant NNS cord-014597-66vd2mdu 590 9 showed show VBD cord-014597-66vd2mdu 590 10 that that IN cord-014597-66vd2mdu 590 11 transfected transfecte VBN cord-014597-66vd2mdu 590 12 High High NNP cord-014597-66vd2mdu 590 13 Five five CD cord-014597-66vd2mdu 590 14 cells cell NNS cord-014597-66vd2mdu 590 15 secreted secrete VBD cord-014597-66vd2mdu 590 16 the the DT cord-014597-66vd2mdu 590 17 Fab Fab NNP cord-014597-66vd2mdu 590 18 fragment fragment NN cord-014597-66vd2mdu 590 19 with with IN cord-014597-66vd2mdu 590 20 antigenbinding antigenbinding NN cord-014597-66vd2mdu 590 21 activity activity NN cord-014597-66vd2mdu 590 22 . . . cord-014597-66vd2mdu 591 1 In in IN cord-014597-66vd2mdu 591 2 static static JJ cord-014597-66vd2mdu 591 3 cultures culture NNS cord-014597-66vd2mdu 591 4 , , , cord-014597-66vd2mdu 591 5 transfection transfection NN cord-014597-66vd2mdu 591 6 and and CC cord-014597-66vd2mdu 591 7 culture culture NN cord-014597-66vd2mdu 591 8 conditions condition NNS cord-014597-66vd2mdu 591 9 , , , cord-014597-66vd2mdu 591 10 such such JJ cord-014597-66vd2mdu 591 11 as as IN cord-014597-66vd2mdu 591 12 Hc Hc NNP cord-014597-66vd2mdu 591 13 : : : cord-014597-66vd2mdu 592 1 Lc Lc NNP cord-014597-66vd2mdu 592 2 gene gene NN cord-014597-66vd2mdu 592 3 ratio ratio NN cord-014597-66vd2mdu 592 4 , , , cord-014597-66vd2mdu 592 5 a a DT cord-014597-66vd2mdu 592 6 serum serum NN cord-014597-66vd2mdu 592 7 - - HYPH cord-014597-66vd2mdu 592 8 free free JJ cord-014597-66vd2mdu 592 9 medium medium NN cord-014597-66vd2mdu 592 10 , , , cord-014597-66vd2mdu 592 11 DNA DNA NNP cord-014597-66vd2mdu 592 12 : : : cord-014597-66vd2mdu 592 13 PEI PEI NNP cord-014597-66vd2mdu 592 14 ratio ratio NN cord-014597-66vd2mdu 592 15 , , , cord-014597-66vd2mdu 592 16 and and CC cord-014597-66vd2mdu 592 17 DNA dna NN cord-014597-66vd2mdu 592 18 amount amount NN cord-014597-66vd2mdu 592 19 per per IN cord-014597-66vd2mdu 592 20 cell cell NN cord-014597-66vd2mdu 592 21 , , , cord-014597-66vd2mdu 592 22 were be VBD cord-014597-66vd2mdu 592 23 successfully successfully RB cord-014597-66vd2mdu 592 24 optimized optimize VBN cord-014597-66vd2mdu 592 25 by by IN cord-014597-66vd2mdu 592 26 flow flow NN cord-014597-66vd2mdu 592 27 cytometry cytometry NN cord-014597-66vd2mdu 592 28 of of IN cord-014597-66vd2mdu 592 29 EGFP EGFP NNP cord-014597-66vd2mdu 592 30 expression expression NN cord-014597-66vd2mdu 592 31 in in IN cord-014597-66vd2mdu 592 32 transfected transfected JJ cord-014597-66vd2mdu 592 33 cells cell NNS cord-014597-66vd2mdu 592 34 and and CC cord-014597-66vd2mdu 592 35 the the DT cord-014597-66vd2mdu 592 36 yield yield NN cord-014597-66vd2mdu 592 37 of of IN cord-014597-66vd2mdu 592 38 the the DT cord-014597-66vd2mdu 592 39 secreted secrete VBN cord-014597-66vd2mdu 592 40 Fab Fab NNP cord-014597-66vd2mdu 592 41 fragment fragment NN cord-014597-66vd2mdu 592 42 measured measure VBN cord-014597-66vd2mdu 592 43 by by IN cord-014597-66vd2mdu 592 44 ELISA ELISA NNP cord-014597-66vd2mdu 592 45 . . . cord-014597-66vd2mdu 593 1 The the DT cord-014597-66vd2mdu 593 2 effects effect NNS cord-014597-66vd2mdu 593 3 of of IN cord-014597-66vd2mdu 593 4 culture culture NN cord-014597-66vd2mdu 593 5 temperature temperature NN cord-014597-66vd2mdu 593 6 and and CC cord-014597-66vd2mdu 593 7 initial initial JJ cord-014597-66vd2mdu 593 8 cell cell NN cord-014597-66vd2mdu 593 9 density density NN cord-014597-66vd2mdu 593 10 were be VBD cord-014597-66vd2mdu 593 11 also also RB cord-014597-66vd2mdu 593 12 examined examine VBN cord-014597-66vd2mdu 593 13 by by IN cord-014597-66vd2mdu 593 14 comparing compare VBG cord-014597-66vd2mdu 593 15 the the DT cord-014597-66vd2mdu 593 16 cell cell NN cord-014597-66vd2mdu 593 17 growth growth NN cord-014597-66vd2mdu 593 18 and and CC cord-014597-66vd2mdu 593 19 the the DT cord-014597-66vd2mdu 593 20 production production NN cord-014597-66vd2mdu 593 21 of of IN cord-014597-66vd2mdu 593 22 Fab fab JJ cord-014597-66vd2mdu 593 23 fragments fragment NNS cord-014597-66vd2mdu 593 24 in in IN cord-014597-66vd2mdu 593 25 shake shake NN cord-014597-66vd2mdu 593 26 - - HYPH cord-014597-66vd2mdu 593 27 flask flask NN cord-014597-66vd2mdu 593 28 cultures culture NNS cord-014597-66vd2mdu 593 29 . . . cord-014597-66vd2mdu 594 1 Under under IN cord-014597-66vd2mdu 594 2 optimal optimal JJ cord-014597-66vd2mdu 594 3 conditions condition NNS cord-014597-66vd2mdu 594 4 ( ( -LRB- cord-014597-66vd2mdu 594 5 medium medium NN cord-014597-66vd2mdu 594 6 , , , cord-014597-66vd2mdu 594 7 PSFM PSFM NNP cord-014597-66vd2mdu 594 8 - - HYPH cord-014597-66vd2mdu 594 9 J1 J1 NNP cord-014597-66vd2mdu 594 10 ( ( -LRB- cord-014597-66vd2mdu 594 11 Wako Wako NNP cord-014597-66vd2mdu 594 12 Pure Pure NNP cord-014597-66vd2mdu 594 13 Chemical Chemical NNP cord-014597-66vd2mdu 594 14 Industries Industries NNPS cord-014597-66vd2mdu 594 15 , , , cord-014597-66vd2mdu 594 16 Japan Japan NNP cord-014597-66vd2mdu 594 17 ) ) -RRB- cord-014597-66vd2mdu 595 1 ; ; : cord-014597-66vd2mdu 595 2 Hc Hc NNP cord-014597-66vd2mdu 595 3 : : : cord-014597-66vd2mdu 595 4 Lc Lc NNP cord-014597-66vd2mdu 595 5 gene gene NN cord-014597-66vd2mdu 595 6 ratio ratio NN cord-014597-66vd2mdu 595 7 , , , cord-014597-66vd2mdu 595 8 3:7 3:7 CD cord-014597-66vd2mdu 595 9 ; ; : cord-014597-66vd2mdu 595 10 DNA DNA NNP cord-014597-66vd2mdu 595 11 , , , cord-014597-66vd2mdu 595 12 5 5 CD cord-014597-66vd2mdu 595 13 μg/(10 μg/(10 CD cord-014597-66vd2mdu 595 14 6 6 CD cord-014597-66vd2mdu 595 15 cells cell NNS cord-014597-66vd2mdu 595 16 ) ) -RRB- cord-014597-66vd2mdu 595 17 ; ; : cord-014597-66vd2mdu 595 18 PEI PEI NNP cord-014597-66vd2mdu 595 19 , , , cord-014597-66vd2mdu 595 20 10 10 CD cord-014597-66vd2mdu 595 21 μg/(10 μg/(10 CD cord-014597-66vd2mdu 595 22 6 6 CD cord-014597-66vd2mdu 595 23 cells cell NNS cord-014597-66vd2mdu 595 24 ) ) -RRB- cord-014597-66vd2mdu 595 25 ; ; , cord-014597-66vd2mdu 595 26 initial initial JJ cord-014597-66vd2mdu 595 27 cell cell NN cord-014597-66vd2mdu 595 28 density density NN cord-014597-66vd2mdu 595 29 , , , cord-014597-66vd2mdu 595 30 1 1 CD cord-014597-66vd2mdu 595 31 x x SYM cord-014597-66vd2mdu 595 32 10 10 CD cord-014597-66vd2mdu 595 33 6 6 CD cord-014597-66vd2mdu 595 34 cells cell NNS cord-014597-66vd2mdu 595 35 / / SYM cord-014597-66vd2mdu 595 36 cm cm NN cord-014597-66vd2mdu 595 37 3 3 CD cord-014597-66vd2mdu 595 38 ; ; : cord-014597-66vd2mdu 595 39 temperature temperature NN cord-014597-66vd2mdu 595 40 , , , cord-014597-66vd2mdu 595 41 24 24 CD cord-014597-66vd2mdu 595 42 ° ° NN cord-014597-66vd2mdu 595 43 C C NNP cord-014597-66vd2mdu 595 44 ) ) -RRB- cord-014597-66vd2mdu 595 45 , , , cord-014597-66vd2mdu 595 46 the the DT cord-014597-66vd2mdu 595 47 yield yield NN cord-014597-66vd2mdu 595 48 of of IN cord-014597-66vd2mdu 595 49 more more JJR cord-014597-66vd2mdu 595 50 than than IN cord-014597-66vd2mdu 595 51 100 100 CD cord-014597-66vd2mdu 595 52 mg mg NNP cord-014597-66vd2mdu 595 53 / / SYM cord-014597-66vd2mdu 595 54 L L NNP cord-014597-66vd2mdu 595 55 of of IN cord-014597-66vd2mdu 595 56 Fab Fab NNP cord-014597-66vd2mdu 595 57 fragment fragment NN cord-014597-66vd2mdu 595 58 was be VBD cord-014597-66vd2mdu 595 59 achieved achieve VBN cord-014597-66vd2mdu 595 60 in in IN cord-014597-66vd2mdu 595 61 5 5 CD cord-014597-66vd2mdu 595 62 days day NNS cord-014597-66vd2mdu 595 63 in in IN cord-014597-66vd2mdu 595 64 a a DT cord-014597-66vd2mdu 595 65 shake shake NN cord-014597-66vd2mdu 595 66 - - HYPH cord-014597-66vd2mdu 595 67 flask flask NN cord-014597-66vd2mdu 595 68 culture culture NN cord-014597-66vd2mdu 595 69 ( ( -LRB- cord-014597-66vd2mdu 595 70 Fig Fig NNP cord-014597-66vd2mdu 595 71 . . . cord-014597-66vd2mdu 595 72 1 1 CD cord-014597-66vd2mdu 595 73 ) ) -RRB- cord-014597-66vd2mdu 595 74 . . . cord-014597-66vd2mdu 596 1 Transfection Transfection NNP cord-014597-66vd2mdu 596 2 did do VBD cord-014597-66vd2mdu 596 3 not not RB cord-014597-66vd2mdu 596 4 significantly significantly RB cord-014597-66vd2mdu 596 5 affect affect VB cord-014597-66vd2mdu 596 6 the the DT cord-014597-66vd2mdu 596 7 growth growth NN cord-014597-66vd2mdu 596 8 of of IN cord-014597-66vd2mdu 596 9 High High NNP cord-014597-66vd2mdu 596 10 Five five CD cord-014597-66vd2mdu 596 11 cells cell NNS cord-014597-66vd2mdu 596 12 as as IN cord-014597-66vd2mdu 596 13 compared compare VBN cord-014597-66vd2mdu 596 14 with with IN cord-014597-66vd2mdu 596 15 untransfected untransfected JJ cord-014597-66vd2mdu 596 16 cells cell NNS cord-014597-66vd2mdu 596 17 . . . cord-014597-66vd2mdu 597 1 Transient transient JJ cord-014597-66vd2mdu 597 2 gene gene NN cord-014597-66vd2mdu 597 3 expression expression NN cord-014597-66vd2mdu 597 4 using use VBG cord-014597-66vd2mdu 597 5 insect insect NN cord-014597-66vd2mdu 597 6 cells cell NNS cord-014597-66vd2mdu 597 7 may may MD cord-014597-66vd2mdu 597 8 offer offer VB cord-014597-66vd2mdu 597 9 a a DT cord-014597-66vd2mdu 597 10 promising promising JJ cord-014597-66vd2mdu 597 11 approach approach NN cord-014597-66vd2mdu 597 12 to to IN cord-014597-66vd2mdu 597 13 high high JJ cord-014597-66vd2mdu 597 14 - - HYPH cord-014597-66vd2mdu 597 15 throughput throughput NN cord-014597-66vd2mdu 597 16 production production NN cord-014597-66vd2mdu 597 17 of of IN cord-014597-66vd2mdu 597 18 candidate candidate NN cord-014597-66vd2mdu 597 19 proteins protein NNS cord-014597-66vd2mdu 597 20 for for IN cord-014597-66vd2mdu 597 21 the the DT cord-014597-66vd2mdu 597 22 development development NN cord-014597-66vd2mdu 597 23 of of IN cord-014597-66vd2mdu 597 24 biologics biologic NNS cord-014597-66vd2mdu 597 25 . . . cord-014597-66vd2mdu 597 26 _SP cord-014597-66vd2mdu 598 1 The the DT cord-014597-66vd2mdu 598 2 increasing increase VBG cord-014597-66vd2mdu 598 3 demand demand NN cord-014597-66vd2mdu 598 4 for for IN cord-014597-66vd2mdu 598 5 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 598 6 produced produce VBN cord-014597-66vd2mdu 598 7 in in IN cord-014597-66vd2mdu 598 8 mammalian mammalian JJ cord-014597-66vd2mdu 598 9 cells cell NNS cord-014597-66vd2mdu 598 10 has have VBZ cord-014597-66vd2mdu 598 11 led lead VBN cord-014597-66vd2mdu 598 12 industries industry NNS cord-014597-66vd2mdu 598 13 to to TO cord-014597-66vd2mdu 598 14 increase increase VB cord-014597-66vd2mdu 598 15 volumetric volumetric JJ cord-014597-66vd2mdu 598 16 productivity productivity NN cord-014597-66vd2mdu 598 17 of of IN cord-014597-66vd2mdu 598 18 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 598 19 through through IN cord-014597-66vd2mdu 598 20 different different JJ cord-014597-66vd2mdu 598 21 strategies strategy NNS cord-014597-66vd2mdu 598 22 [ [ -LRB- cord-014597-66vd2mdu 598 23 1 1 CD cord-014597-66vd2mdu 598 24 , , , cord-014597-66vd2mdu 598 25 2 2 CD cord-014597-66vd2mdu 598 26 , , , cord-014597-66vd2mdu 598 27 3 3 CD cord-014597-66vd2mdu 598 28 ] ] -RRB- cord-014597-66vd2mdu 598 29 . . . cord-014597-66vd2mdu 599 1 In in IN cord-014597-66vd2mdu 599 2 this this DT cord-014597-66vd2mdu 599 3 context context NN cord-014597-66vd2mdu 599 4 , , , cord-014597-66vd2mdu 599 5 fedbatch fedbatch NN cord-014597-66vd2mdu 599 6 and and CC cord-014597-66vd2mdu 599 7 perfusion perfusion NN cord-014597-66vd2mdu 599 8 cultures culture NNS cord-014597-66vd2mdu 599 9 have have VBP cord-014597-66vd2mdu 599 10 attracted attract VBN cord-014597-66vd2mdu 599 11 more more JJR cord-014597-66vd2mdu 599 12 interest interest NN cord-014597-66vd2mdu 599 13 than than IN cord-014597-66vd2mdu 599 14 conventional conventional JJ cord-014597-66vd2mdu 599 15 batch batch NN cord-014597-66vd2mdu 599 16 processes process NNS cord-014597-66vd2mdu 599 17 . . . cord-014597-66vd2mdu 600 1 The the DT cord-014597-66vd2mdu 600 2 efficient efficient JJ cord-014597-66vd2mdu 600 3 application application NN cord-014597-66vd2mdu 600 4 of of IN cord-014597-66vd2mdu 600 5 such such JJ cord-014597-66vd2mdu 600 6 alternative alternative JJ cord-014597-66vd2mdu 600 7 processes process NNS cord-014597-66vd2mdu 600 8 requires require VBZ cord-014597-66vd2mdu 600 9 the the DT cord-014597-66vd2mdu 600 10 availability availability NN cord-014597-66vd2mdu 600 11 of of IN cord-014597-66vd2mdu 600 12 reliable reliable JJ cord-014597-66vd2mdu 600 13 on on IN cord-014597-66vd2mdu 600 14 - - HYPH cord-014597-66vd2mdu 600 15 line line NN cord-014597-66vd2mdu 600 16 measuring measuring NN cord-014597-66vd2mdu 600 17 tools tool NNS cord-014597-66vd2mdu 600 18 for for IN cord-014597-66vd2mdu 600 19 cell cell NN cord-014597-66vd2mdu 600 20 density density NN cord-014597-66vd2mdu 600 21 and and CC cord-014597-66vd2mdu 600 22 cell cell NN cord-014597-66vd2mdu 600 23 metabolic metabolic JJ cord-014597-66vd2mdu 600 24 activity activity NN cord-014597-66vd2mdu 600 25 estimation estimation NN cord-014597-66vd2mdu 600 26 [ [ -LRB- cord-014597-66vd2mdu 600 27 4 4 CD cord-014597-66vd2mdu 600 28 ] ] -RRB- cord-014597-66vd2mdu 600 29 . . . cord-014597-66vd2mdu 601 1 The the DT cord-014597-66vd2mdu 601 2 comparison comparison NN cord-014597-66vd2mdu 601 3 of of IN cord-014597-66vd2mdu 601 4 different different JJ cord-014597-66vd2mdu 601 5 culture culture NN cord-014597-66vd2mdu 601 6 strategies strategy NNS cord-014597-66vd2mdu 601 7 for for IN cord-014597-66vd2mdu 601 8 HEK293 HEK293 NNP cord-014597-66vd2mdu 601 9 cell cell NN cord-014597-66vd2mdu 601 10 line line NN cord-014597-66vd2mdu 601 11 producing produce VBG cord-014597-66vd2mdu 601 12 IFN IFN NNP cord-014597-66vd2mdu 601 13 - - HYPH cord-014597-66vd2mdu 601 14 γ γ NNP cord-014597-66vd2mdu 601 15 are be VBP cord-014597-66vd2mdu 601 16 presented present VBN cord-014597-66vd2mdu 601 17 below below IN cord-014597-66vd2mdu 601 18 : : : cord-014597-66vd2mdu 601 19 batch batch NN cord-014597-66vd2mdu 601 20 , , , cord-014597-66vd2mdu 601 21 fortified fortified JJ cord-014597-66vd2mdu 601 22 batch batch NN cord-014597-66vd2mdu 601 23 and and CC cord-014597-66vd2mdu 601 24 fed fed JJ cord-014597-66vd2mdu 601 25 - - HYPH cord-014597-66vd2mdu 601 26 batch batch NN cord-014597-66vd2mdu 601 27 . . . cord-014597-66vd2mdu 602 1 In in IN cord-014597-66vd2mdu 602 2 this this DT cord-014597-66vd2mdu 602 3 context context NN cord-014597-66vd2mdu 602 4 , , , cord-014597-66vd2mdu 602 5 a a DT cord-014597-66vd2mdu 602 6 new new JJ cord-014597-66vd2mdu 602 7 robust robust JJ cord-014597-66vd2mdu 602 8 feeding feeding NN cord-014597-66vd2mdu 602 9 strategy strategy NN cord-014597-66vd2mdu 602 10 based base VBN cord-014597-66vd2mdu 602 11 on on IN cord-014597-66vd2mdu 602 12 the the DT cord-014597-66vd2mdu 602 13 monitoring monitoring NN cord-014597-66vd2mdu 602 14 of of IN cord-014597-66vd2mdu 602 15 alkali alkali JJ cord-014597-66vd2mdu 602 16 buffer buffer NN cord-014597-66vd2mdu 602 17 addition addition NN cord-014597-66vd2mdu 602 18 was be VBD cord-014597-66vd2mdu 602 19 applied apply VBN cord-014597-66vd2mdu 602 20 for for IN cord-014597-66vd2mdu 602 21 the the DT cord-014597-66vd2mdu 602 22 estimation estimation NN cord-014597-66vd2mdu 602 23 of of IN cord-014597-66vd2mdu 602 24 nutrient nutrient NN cord-014597-66vd2mdu 602 25 requirements requirement NNS cord-014597-66vd2mdu 602 26 . . . cord-014597-66vd2mdu 603 1 This this DT cord-014597-66vd2mdu 603 2 method method NN cord-014597-66vd2mdu 603 3 allows allow VBZ cord-014597-66vd2mdu 603 4 to to TO cord-014597-66vd2mdu 603 5 increase increase VB cord-014597-66vd2mdu 603 6 cell cell NN cord-014597-66vd2mdu 603 7 density density NN cord-014597-66vd2mdu 603 8 and and CC cord-014597-66vd2mdu 603 9 product product NN cord-014597-66vd2mdu 603 10 titer titer NN cord-014597-66vd2mdu 603 11 compared compare VBN cord-014597-66vd2mdu 603 12 with with IN cord-014597-66vd2mdu 603 13 the the DT cord-014597-66vd2mdu 603 14 other other JJ cord-014597-66vd2mdu 603 15 strategies strategy NNS cord-014597-66vd2mdu 603 16 assessed assess VBN cord-014597-66vd2mdu 603 17 . . . cord-014597-66vd2mdu 604 1 Three three CD cord-014597-66vd2mdu 604 2 different different JJ cord-014597-66vd2mdu 604 3 culture culture NN cord-014597-66vd2mdu 604 4 strategies strategy NNS cord-014597-66vd2mdu 604 5 were be VBD cord-014597-66vd2mdu 604 6 carried carry VBN cord-014597-66vd2mdu 604 7 out out RP cord-014597-66vd2mdu 604 8 in in IN cord-014597-66vd2mdu 604 9 2-litre 2-litre CD cord-014597-66vd2mdu 604 10 Biostat Biostat NNP cord-014597-66vd2mdu 604 11 B B NNP cord-014597-66vd2mdu 604 12 - - HYPH cord-014597-66vd2mdu 604 13 DCU DCU NNP cord-014597-66vd2mdu 604 14 II II NNP cord-014597-66vd2mdu 604 15 bioreactor bioreactor NN cord-014597-66vd2mdu 604 16 . . . cord-014597-66vd2mdu 605 1 First first RB cord-014597-66vd2mdu 605 2 , , , cord-014597-66vd2mdu 605 3 a a DT cord-014597-66vd2mdu 605 4 reference reference NN cord-014597-66vd2mdu 605 5 batch batch NN cord-014597-66vd2mdu 605 6 and and CC cord-014597-66vd2mdu 605 7 a a DT cord-014597-66vd2mdu 605 8 batch batch NN cord-014597-66vd2mdu 605 9 using use VBG cord-014597-66vd2mdu 605 10 fortified fortified JJ cord-014597-66vd2mdu 605 11 medium medium NN cord-014597-66vd2mdu 605 12 ( ( -LRB- cord-014597-66vd2mdu 605 13 nutrient nutrient NN cord-014597-66vd2mdu 605 14 enriched enrich VBN cord-014597-66vd2mdu 605 15 medium medium NN cord-014597-66vd2mdu 605 16 ) ) -RRB- cord-014597-66vd2mdu 605 17 were be VBD cord-014597-66vd2mdu 605 18 run run VBN cord-014597-66vd2mdu 605 19 and and CC cord-014597-66vd2mdu 605 20 assessed assess VBN cord-014597-66vd2mdu 605 21 in in IN cord-014597-66vd2mdu 605 22 terms term NNS cord-014597-66vd2mdu 605 23 of of IN cord-014597-66vd2mdu 605 24 Viable viable JJ cord-014597-66vd2mdu 605 25 Cell cell NN cord-014597-66vd2mdu 605 26 Density density NN cord-014597-66vd2mdu 605 27 ( ( -LRB- cord-014597-66vd2mdu 605 28 VCD vcd NN cord-014597-66vd2mdu 605 29 ) ) -RRB- cord-014597-66vd2mdu 605 30 and and CC cord-014597-66vd2mdu 605 31 product product NN cord-014597-66vd2mdu 605 32 titer titer NN cord-014597-66vd2mdu 605 33 , , , cord-014597-66vd2mdu 605 34 and and CC cord-014597-66vd2mdu 605 35 set set VBD cord-014597-66vd2mdu 605 36 as as IN cord-014597-66vd2mdu 605 37 initial initial JJ cord-014597-66vd2mdu 605 38 references reference NNS cord-014597-66vd2mdu 605 39 . . . cord-014597-66vd2mdu 606 1 Then then RB cord-014597-66vd2mdu 606 2 , , , cord-014597-66vd2mdu 606 3 a a DT cord-014597-66vd2mdu 606 4 fed feed VBN cord-014597-66vd2mdu 606 5 - - HYPH cord-014597-66vd2mdu 606 6 batch batch NN cord-014597-66vd2mdu 606 7 was be VBD cord-014597-66vd2mdu 606 8 performed perform VBN cord-014597-66vd2mdu 606 9 applying apply VBG cord-014597-66vd2mdu 606 10 a a DT cord-014597-66vd2mdu 606 11 feeding feeding NN cord-014597-66vd2mdu 606 12 strategy strategy NN cord-014597-66vd2mdu 606 13 based base VBN cord-014597-66vd2mdu 606 14 on on IN cord-014597-66vd2mdu 606 15 the the DT cord-014597-66vd2mdu 606 16 nutrient nutrient NN cord-014597-66vd2mdu 606 17 requirements requirement NNS cord-014597-66vd2mdu 606 18 estimation estimation NN cord-014597-66vd2mdu 606 19 by by IN cord-014597-66vd2mdu 606 20 monitoring monitor VBG cord-014597-66vd2mdu 606 21 the the DT cord-014597-66vd2mdu 606 22 alkali alkali JJ cord-014597-66vd2mdu 606 23 buffer buffer NN cord-014597-66vd2mdu 606 24 addition addition NN cord-014597-66vd2mdu 606 25 used use VBN cord-014597-66vd2mdu 606 26 for for IN cord-014597-66vd2mdu 606 27 the the DT cord-014597-66vd2mdu 606 28 control control NN cord-014597-66vd2mdu 606 29 of of IN cord-014597-66vd2mdu 606 30 pH. ph. NN cord-014597-66vd2mdu 606 31 Results Results NNP cord-014597-66vd2mdu 606 32 VCD VCD NNP cord-014597-66vd2mdu 606 33 and and CC cord-014597-66vd2mdu 606 34 product product NN cord-014597-66vd2mdu 606 35 titer titer NN cord-014597-66vd2mdu 606 36 achieved achieve VBN cord-014597-66vd2mdu 606 37 for for IN cord-014597-66vd2mdu 606 38 the the DT cord-014597-66vd2mdu 606 39 different different JJ cord-014597-66vd2mdu 606 40 culture culture NN cord-014597-66vd2mdu 606 41 strategies strategy NNS cord-014597-66vd2mdu 606 42 assessed assess VBD cord-014597-66vd2mdu 606 43 ( ( -LRB- cord-014597-66vd2mdu 606 44 batch batch NN cord-014597-66vd2mdu 606 45 , , , cord-014597-66vd2mdu 606 46 fortified fortified JJ cord-014597-66vd2mdu 606 47 - - HYPH cord-014597-66vd2mdu 606 48 batch batch NN cord-014597-66vd2mdu 606 49 and and CC cord-014597-66vd2mdu 606 50 fed fed JJ cord-014597-66vd2mdu 606 51 - - HYPH cord-014597-66vd2mdu 606 52 batch batch NN cord-014597-66vd2mdu 606 53 ) ) -RRB- cord-014597-66vd2mdu 606 54 are be VBP cord-014597-66vd2mdu 606 55 presented present VBN cord-014597-66vd2mdu 606 56 in in IN cord-014597-66vd2mdu 606 57 table table NN cord-014597-66vd2mdu 606 58 1 1 CD cord-014597-66vd2mdu 606 59 . . . cord-014597-66vd2mdu 607 1 In in IN cord-014597-66vd2mdu 607 2 fortified fortified JJ cord-014597-66vd2mdu 607 3 batch batch NN cord-014597-66vd2mdu 607 4 an an DT cord-014597-66vd2mdu 607 5 increase increase NN cord-014597-66vd2mdu 607 6 in in IN cord-014597-66vd2mdu 607 7 VCD vcd NN cord-014597-66vd2mdu 607 8 of of IN cord-014597-66vd2mdu 607 9 145 145 CD cord-014597-66vd2mdu 607 10 % % NN cord-014597-66vd2mdu 607 11 and and CC cord-014597-66vd2mdu 607 12 also also RB cord-014597-66vd2mdu 607 13 350 350 CD cord-014597-66vd2mdu 607 14 % % NN cord-014597-66vd2mdu 607 15 in in IN cord-014597-66vd2mdu 607 16 product product NN cord-014597-66vd2mdu 607 17 titer titer NN cord-014597-66vd2mdu 607 18 were be VBD cord-014597-66vd2mdu 607 19 obtained obtain VBN cord-014597-66vd2mdu 607 20 compared compare VBN cord-014597-66vd2mdu 607 21 with with IN cord-014597-66vd2mdu 607 22 batch batch NN cord-014597-66vd2mdu 607 23 . . . cord-014597-66vd2mdu 608 1 In in IN cord-014597-66vd2mdu 608 2 the the DT cord-014597-66vd2mdu 608 3 fed fed JJ cord-014597-66vd2mdu 608 4 - - HYPH cord-014597-66vd2mdu 608 5 batch batch NN cord-014597-66vd2mdu 608 6 culture culture NN cord-014597-66vd2mdu 608 7 carried carry VBN cord-014597-66vd2mdu 608 8 out out RP cord-014597-66vd2mdu 608 9 ( ( -LRB- cord-014597-66vd2mdu 608 10 Fig Fig NNP cord-014597-66vd2mdu 608 11 . . . cord-014597-66vd2mdu 608 12 1 1 CD cord-014597-66vd2mdu 608 13 ) ) -RRB- cord-014597-66vd2mdu 608 14 , , , cord-014597-66vd2mdu 608 15 we -PRON- PRP cord-014597-66vd2mdu 608 16 observed observe VBD cord-014597-66vd2mdu 608 17 that that IN cord-014597-66vd2mdu 608 18 alkali alkali JJ cord-014597-66vd2mdu 608 19 buffer buffer NN cord-014597-66vd2mdu 608 20 addition addition NN cord-014597-66vd2mdu 608 21 profile profile NN cord-014597-66vd2mdu 608 22 matched match VBD cord-014597-66vd2mdu 608 23 the the DT cord-014597-66vd2mdu 608 24 VCD vcd NN cord-014597-66vd2mdu 608 25 evolution evolution NN cord-014597-66vd2mdu 608 26 trend trend NN cord-014597-66vd2mdu 608 27 . . . cord-014597-66vd2mdu 609 1 Thus thus RB cord-014597-66vd2mdu 609 2 , , , cord-014597-66vd2mdu 609 3 the the DT cord-014597-66vd2mdu 609 4 monitoring monitoring NN cord-014597-66vd2mdu 609 5 of of IN cord-014597-66vd2mdu 609 6 alkali alkali JJ cord-014597-66vd2mdu 609 7 buffer buffer NN cord-014597-66vd2mdu 609 8 addition addition NN cord-014597-66vd2mdu 609 9 was be VBD cord-014597-66vd2mdu 609 10 used use VBN cord-014597-66vd2mdu 609 11 for for IN cord-014597-66vd2mdu 609 12 estimating estimate VBG cord-014597-66vd2mdu 609 13 the the DT cord-014597-66vd2mdu 609 14 nutrients nutrient NNS cord-014597-66vd2mdu 609 15 requirements requirement NNS cord-014597-66vd2mdu 609 16 ( ( -LRB- cord-014597-66vd2mdu 609 17 i.e. i.e. FW cord-014597-66vd2mdu 609 18 the the DT cord-014597-66vd2mdu 609 19 volume volume NN cord-014597-66vd2mdu 609 20 of of IN cord-014597-66vd2mdu 609 21 feeding feed VBG cord-014597-66vd2mdu 609 22 medium medium NN cord-014597-66vd2mdu 609 23 ) ) -RRB- cord-014597-66vd2mdu 609 24 at at IN cord-014597-66vd2mdu 609 25 any any DT cord-014597-66vd2mdu 609 26 time time NN cord-014597-66vd2mdu 609 27 during during IN cord-014597-66vd2mdu 609 28 the the DT cord-014597-66vd2mdu 609 29 fed fed NNP cord-014597-66vd2mdu 609 30 batch batch NN cord-014597-66vd2mdu 609 31 phase phase NN cord-014597-66vd2mdu 609 32 . . . cord-014597-66vd2mdu 610 1 The the DT cord-014597-66vd2mdu 610 2 feeding feeding NN cord-014597-66vd2mdu 610 3 strategy strategy NN cord-014597-66vd2mdu 610 4 based base VBN cord-014597-66vd2mdu 610 5 on on IN cord-014597-66vd2mdu 610 6 alkali alkali JJ cord-014597-66vd2mdu 610 7 buffer buffer NN cord-014597-66vd2mdu 610 8 addition addition NN cord-014597-66vd2mdu 610 9 enabled enable VBD cord-014597-66vd2mdu 610 10 to to TO cord-014597-66vd2mdu 610 11 maintain maintain VB cord-014597-66vd2mdu 610 12 glucose glucose NN cord-014597-66vd2mdu 610 13 concentration concentration NN cord-014597-66vd2mdu 610 14 set set VBN cord-014597-66vd2mdu 610 15 point point NN cord-014597-66vd2mdu 610 16 therein therein IN cord-014597-66vd2mdu 610 17 a a DT cord-014597-66vd2mdu 610 18 narrow narrow JJ cord-014597-66vd2mdu 610 19 range range NN cord-014597-66vd2mdu 610 20 during during IN cord-014597-66vd2mdu 610 21 fed fed JJ cord-014597-66vd2mdu 610 22 - - HYPH cord-014597-66vd2mdu 610 23 batch batch NN cord-014597-66vd2mdu 610 24 phase phase NN cord-014597-66vd2mdu 610 25 ( ( -LRB- cord-014597-66vd2mdu 610 26 around around RB cord-014597-66vd2mdu 610 27 20 20 CD cord-014597-66vd2mdu 610 28 mM mm CD cord-014597-66vd2mdu 610 29 ) ) -RRB- cord-014597-66vd2mdu 610 30 . . . cord-014597-66vd2mdu 611 1 As as IN cord-014597-66vd2mdu 611 2 a a DT cord-014597-66vd2mdu 611 3 result result NN cord-014597-66vd2mdu 611 4 , , , cord-014597-66vd2mdu 611 5 higher high JJR cord-014597-66vd2mdu 611 6 VCD vcd NN cord-014597-66vd2mdu 611 7 ( ( -LRB- cord-014597-66vd2mdu 611 8 16.6·10 16.6·10 CD cord-014597-66vd2mdu 611 9 6 6 CD cord-014597-66vd2mdu 611 10 cells cell NNS cord-014597-66vd2mdu 611 11 / / SYM cord-014597-66vd2mdu 611 12 mL ml NN cord-014597-66vd2mdu 611 13 ) ) -RRB- cord-014597-66vd2mdu 611 14 was be VBD cord-014597-66vd2mdu 611 15 obtained obtain VBN cord-014597-66vd2mdu 611 16 when when WRB cord-014597-66vd2mdu 611 17 compared compare VBN cord-014597-66vd2mdu 611 18 with with IN cord-014597-66vd2mdu 611 19 both both DT cord-014597-66vd2mdu 611 20 batch batch JJ cord-014597-66vd2mdu 611 21 references reference NNS cord-014597-66vd2mdu 611 22 : : : cord-014597-66vd2mdu 611 23 VCD VCD NNP cord-014597-66vd2mdu 611 24 was be VBD cord-014597-66vd2mdu 611 25 enhanced enhance VBN cord-014597-66vd2mdu 611 26 to to IN cord-014597-66vd2mdu 611 27 241 241 CD cord-014597-66vd2mdu 611 28 % % NN cord-014597-66vd2mdu 611 29 and and CC cord-014597-66vd2mdu 611 30 39 39 CD cord-014597-66vd2mdu 611 31 % % NN cord-014597-66vd2mdu 611 32 and and CC cord-014597-66vd2mdu 611 33 an an DT cord-014597-66vd2mdu 611 34 increase increase NN cord-014597-66vd2mdu 611 35 up up RB cord-014597-66vd2mdu 611 36 to to TO cord-014597-66vd2mdu 611 37 381 381 CD cord-014597-66vd2mdu 611 38 % % NN cord-014597-66vd2mdu 611 39 and and CC cord-014597-66vd2mdu 611 40 7 7 CD cord-014597-66vd2mdu 611 41 % % NN cord-014597-66vd2mdu 611 42 in in IN cord-014597-66vd2mdu 611 43 product product NN cord-014597-66vd2mdu 611 44 titer titer NN cord-014597-66vd2mdu 611 45 in in IN cord-014597-66vd2mdu 611 46 respect respect NN cord-014597-66vd2mdu 611 47 to to TO cord-014597-66vd2mdu 611 48 batch batch VB cord-014597-66vd2mdu 611 49 and and CC cord-014597-66vd2mdu 611 50 fortified fortified JJ cord-014597-66vd2mdu 611 51 batch batch NN cord-014597-66vd2mdu 611 52 respectively respectively RB cord-014597-66vd2mdu 611 53 . . . cord-014597-66vd2mdu 612 1 The the DT cord-014597-66vd2mdu 612 2 results result NNS cord-014597-66vd2mdu 612 3 prove prove VBP cord-014597-66vd2mdu 612 4 that that IN cord-014597-66vd2mdu 612 5 fed feed VBN cord-014597-66vd2mdu 612 6 - - HYPH cord-014597-66vd2mdu 612 7 batch batch NN cord-014597-66vd2mdu 612 8 strategy strategy NN cord-014597-66vd2mdu 612 9 based base VBN cord-014597-66vd2mdu 612 10 on on IN cord-014597-66vd2mdu 612 11 the the DT cord-014597-66vd2mdu 612 12 alkali alkali JJ cord-014597-66vd2mdu 612 13 buffer buffer NN cord-014597-66vd2mdu 612 14 addition addition NN cord-014597-66vd2mdu 612 15 is be VBZ cord-014597-66vd2mdu 612 16 a a DT cord-014597-66vd2mdu 612 17 robust robust JJ cord-014597-66vd2mdu 612 18 on on IN cord-014597-66vd2mdu 612 19 - - HYPH cord-014597-66vd2mdu 612 20 line line NN cord-014597-66vd2mdu 612 21 monitoring monitoring NN cord-014597-66vd2mdu 612 22 method method NN cord-014597-66vd2mdu 612 23 that that WDT cord-014597-66vd2mdu 612 24 enables enable VBZ cord-014597-66vd2mdu 612 25 to to TO cord-014597-66vd2mdu 612 26 optimize optimize VB cord-014597-66vd2mdu 612 27 the the DT cord-014597-66vd2mdu 612 28 feeding feeding NN cord-014597-66vd2mdu 612 29 strategy strategy NN cord-014597-66vd2mdu 612 30 in in IN cord-014597-66vd2mdu 612 31 a a DT cord-014597-66vd2mdu 612 32 fed feed VBN cord-014597-66vd2mdu 612 33 - - HYPH cord-014597-66vd2mdu 612 34 batch batch NN cord-014597-66vd2mdu 612 35 cultures culture NNS cord-014597-66vd2mdu 612 36 . . . cord-014597-66vd2mdu 613 1 Three three CD cord-014597-66vd2mdu 613 2 different different JJ cord-014597-66vd2mdu 613 3 culture culture NN cord-014597-66vd2mdu 613 4 strategies strategy NNS cord-014597-66vd2mdu 613 5 have have VBP cord-014597-66vd2mdu 613 6 been be VBN cord-014597-66vd2mdu 613 7 tested test VBN cord-014597-66vd2mdu 613 8 in in IN cord-014597-66vd2mdu 613 9 bioreactor bioreactor NN cord-014597-66vd2mdu 613 10 with with IN cord-014597-66vd2mdu 613 11 a a DT cord-014597-66vd2mdu 613 12 HEK293 HEK293 NNP cord-014597-66vd2mdu 613 13 cell cell NN cord-014597-66vd2mdu 613 14 line line NN cord-014597-66vd2mdu 613 15 producing produce VBG cord-014597-66vd2mdu 613 16 IFN IFN NNP cord-014597-66vd2mdu 613 17 - - HYPH cord-014597-66vd2mdu 613 18 γ γ NNP cord-014597-66vd2mdu 613 19 . . . cord-014597-66vd2mdu 614 1 Results result NNS cord-014597-66vd2mdu 614 2 show show VBP cord-014597-66vd2mdu 614 3 as as IN cord-014597-66vd2mdu 614 4 the the DT cord-014597-66vd2mdu 614 5 higher high JJR cord-014597-66vd2mdu 614 6 VCD vcd NN cord-014597-66vd2mdu 614 7 is be VBZ cord-014597-66vd2mdu 614 8 reached reach VBN cord-014597-66vd2mdu 614 9 , , , cord-014597-66vd2mdu 614 10 the the DT cord-014597-66vd2mdu 614 11 higher high JJR cord-014597-66vd2mdu 614 12 product product NN cord-014597-66vd2mdu 614 13 concentration concentration NN cord-014597-66vd2mdu 614 14 is be VBZ cord-014597-66vd2mdu 614 15 achieved achieve VBN cord-014597-66vd2mdu 614 16 . . . cord-014597-66vd2mdu 615 1 Therefore therefore RB cord-014597-66vd2mdu 615 2 , , , cord-014597-66vd2mdu 615 3 from from IN cord-014597-66vd2mdu 615 4 bioprocess bioprocess NNP cord-014597-66vd2mdu 615 5 development development NNP cord-014597-66vd2mdu 615 6 point point NN cord-014597-66vd2mdu 615 7 of of IN cord-014597-66vd2mdu 615 8 view view NN cord-014597-66vd2mdu 615 9 , , , cord-014597-66vd2mdu 615 10 it -PRON- PRP cord-014597-66vd2mdu 615 11 is be VBZ cord-014597-66vd2mdu 615 12 very very RB cord-014597-66vd2mdu 615 13 interesting interesting JJ cord-014597-66vd2mdu 615 14 to to TO cord-014597-66vd2mdu 615 15 implement implement VB cord-014597-66vd2mdu 615 16 strategies strategy NNS cord-014597-66vd2mdu 615 17 with with IN cord-014597-66vd2mdu 615 18 higher high JJR cord-014597-66vd2mdu 615 19 VCD vcd NN cord-014597-66vd2mdu 615 20 outcome outcome NN cord-014597-66vd2mdu 615 21 , , , cord-014597-66vd2mdu 615 22 such such JJ cord-014597-66vd2mdu 615 23 as as IN cord-014597-66vd2mdu 615 24 fed fed JJ cord-014597-66vd2mdu 615 25 - - HYPH cord-014597-66vd2mdu 615 26 batch batch NN cord-014597-66vd2mdu 615 27 operation operation NN cord-014597-66vd2mdu 615 28 mode mode NN cord-014597-66vd2mdu 615 29 . . . cord-014597-66vd2mdu 616 1 In in IN cord-014597-66vd2mdu 616 2 this this DT cord-014597-66vd2mdu 616 3 context context NN cord-014597-66vd2mdu 616 4 , , , cord-014597-66vd2mdu 616 5 a a DT cord-014597-66vd2mdu 616 6 new new JJ cord-014597-66vd2mdu 616 7 robust robust JJ cord-014597-66vd2mdu 616 8 method method NN cord-014597-66vd2mdu 616 9 for for IN cord-014597-66vd2mdu 616 10 VCD vcd NN cord-014597-66vd2mdu 616 11 estimation estimation NN cord-014597-66vd2mdu 616 12 in in IN cord-014597-66vd2mdu 616 13 fed fed NNP cord-014597-66vd2mdu 616 14 - - HYPH cord-014597-66vd2mdu 616 15 batch batch NNP cord-014597-66vd2mdu 616 16 was be VBD cord-014597-66vd2mdu 616 17 applied apply VBN cord-014597-66vd2mdu 616 18 . . . cord-014597-66vd2mdu 617 1 The the DT cord-014597-66vd2mdu 617 2 alkali alkali JJ cord-014597-66vd2mdu 617 3 buffer buffer NN cord-014597-66vd2mdu 617 4 addition addition NN cord-014597-66vd2mdu 617 5 necessary necessary JJ cord-014597-66vd2mdu 617 6 for for IN cord-014597-66vd2mdu 617 7 maintaining maintain VBG cord-014597-66vd2mdu 617 8 the the DT cord-014597-66vd2mdu 617 9 pH pH NNP cord-014597-66vd2mdu 617 10 set set NN cord-014597-66vd2mdu 617 11 - - HYPH cord-014597-66vd2mdu 617 12 point point NN cord-014597-66vd2mdu 617 13 is be VBZ cord-014597-66vd2mdu 617 14 an an DT cord-014597-66vd2mdu 617 15 on on IN cord-014597-66vd2mdu 617 16 - - HYPH cord-014597-66vd2mdu 617 17 line line NN cord-014597-66vd2mdu 617 18 reliable reliable JJ cord-014597-66vd2mdu 617 19 and and CC cord-014597-66vd2mdu 617 20 easy easy JJ cord-014597-66vd2mdu 617 21 measuring measuring NN cord-014597-66vd2mdu 617 22 variable variable NN cord-014597-66vd2mdu 617 23 that that WDT cord-014597-66vd2mdu 617 24 provides provide VBZ cord-014597-66vd2mdu 617 25 information information NN cord-014597-66vd2mdu 617 26 about about IN cord-014597-66vd2mdu 617 27 by by IN cord-014597-66vd2mdu 617 28 - - HYPH cord-014597-66vd2mdu 617 29 products product NNS cord-014597-66vd2mdu 617 30 formation formation NN cord-014597-66vd2mdu 617 31 ( ( -LRB- cord-014597-66vd2mdu 617 32 mainly mainly RB cord-014597-66vd2mdu 617 33 lactic lactic JJ cord-014597-66vd2mdu 617 34 acid acid NN cord-014597-66vd2mdu 617 35 ) ) -RRB- cord-014597-66vd2mdu 617 36 . . . cord-014597-66vd2mdu 618 1 The the DT cord-014597-66vd2mdu 618 2 monitoring monitoring NN cord-014597-66vd2mdu 618 3 of of IN cord-014597-66vd2mdu 618 4 this this DT cord-014597-66vd2mdu 618 5 variable variable NN cord-014597-66vd2mdu 618 6 can can MD cord-014597-66vd2mdu 618 7 provide provide VB cord-014597-66vd2mdu 618 8 information information NN cord-014597-66vd2mdu 618 9 about about IN cord-014597-66vd2mdu 618 10 the the DT cord-014597-66vd2mdu 618 11 cell cell NN cord-014597-66vd2mdu 618 12 concentration concentration NN cord-014597-66vd2mdu 618 13 , , , cord-014597-66vd2mdu 618 14 activity activity NN cord-014597-66vd2mdu 618 15 and and CC cord-014597-66vd2mdu 618 16 metabolism metabolism NN cord-014597-66vd2mdu 618 17 , , , cord-014597-66vd2mdu 618 18 to to TO cord-014597-66vd2mdu 618 19 detect detect VB cord-014597-66vd2mdu 618 20 changes change NNS cord-014597-66vd2mdu 618 21 in in IN cord-014597-66vd2mdu 618 22 culture culture NN cord-014597-66vd2mdu 618 23 . . . cord-014597-66vd2mdu 619 1 Besides besides IN cord-014597-66vd2mdu 619 2 that that DT cord-014597-66vd2mdu 619 3 , , , cord-014597-66vd2mdu 619 4 a a DT cord-014597-66vd2mdu 619 5 relationship relationship NN cord-014597-66vd2mdu 619 6 between between IN cord-014597-66vd2mdu 619 7 alkali alkali NN cord-014597-66vd2mdu 619 8 buffer buffer NN cord-014597-66vd2mdu 619 9 addition addition NN cord-014597-66vd2mdu 619 10 and and CC cord-014597-66vd2mdu 619 11 VCD vcd NN cord-014597-66vd2mdu 619 12 can can MD cord-014597-66vd2mdu 619 13 be be VB cord-014597-66vd2mdu 619 14 established establish VBN cord-014597-66vd2mdu 619 15 since since IN cord-014597-66vd2mdu 619 16 the the DT cord-014597-66vd2mdu 619 17 first first JJ cord-014597-66vd2mdu 619 18 is be VBZ cord-014597-66vd2mdu 619 19 strongly strongly RB cord-014597-66vd2mdu 619 20 correlated correlate VBN cord-014597-66vd2mdu 619 21 with with IN cord-014597-66vd2mdu 619 22 cell cell NN cord-014597-66vd2mdu 619 23 growth growth NN cord-014597-66vd2mdu 619 24 and and CC cord-014597-66vd2mdu 619 25 metabolites metabolite NNS cord-014597-66vd2mdu 619 26 consumption consumption NN cord-014597-66vd2mdu 619 27 / / SYM cord-014597-66vd2mdu 619 28 formation formation NN cord-014597-66vd2mdu 619 29 . . . cord-014597-66vd2mdu 620 1 The the DT cord-014597-66vd2mdu 620 2 application application NN cord-014597-66vd2mdu 620 3 of of IN cord-014597-66vd2mdu 620 4 alkali alkali JJ cord-014597-66vd2mdu 620 5 buffer buffer NN cord-014597-66vd2mdu 620 6 addition addition NN cord-014597-66vd2mdu 620 7 measure measure NN cord-014597-66vd2mdu 620 8 to to TO cord-014597-66vd2mdu 620 9 implement implement VB cord-014597-66vd2mdu 620 10 an an DT cord-014597-66vd2mdu 620 11 optimal optimal JJ cord-014597-66vd2mdu 620 12 feeding feeding NN cord-014597-66vd2mdu 620 13 strategy strategy NN cord-014597-66vd2mdu 620 14 in in IN cord-014597-66vd2mdu 620 15 fed fed NNP cord-014597-66vd2mdu 620 16 - - HYPH cord-014597-66vd2mdu 620 17 batch batch NN cord-014597-66vd2mdu 620 18 permits permit NNS cord-014597-66vd2mdu 620 19 to to TO cord-014597-66vd2mdu 620 20 enhance enhance VB cord-014597-66vd2mdu 620 21 VCD vcd NN cord-014597-66vd2mdu 620 22 and and CC cord-014597-66vd2mdu 620 23 product product NN cord-014597-66vd2mdu 620 24 titer titer NN cord-014597-66vd2mdu 620 25 when when WRB cord-014597-66vd2mdu 620 26 comparing compare VBG cord-014597-66vd2mdu 620 27 with with IN cord-014597-66vd2mdu 620 28 batch batch NN cord-014597-66vd2mdu 620 29 strategies strategy NNS cord-014597-66vd2mdu 620 30 . . . cord-014597-66vd2mdu 621 1 A a DT cord-014597-66vd2mdu 621 2 novel novel JJ cord-014597-66vd2mdu 621 3 approach approach NN cord-014597-66vd2mdu 621 4 to to IN cord-014597-66vd2mdu 621 5 high high JJ cord-014597-66vd2mdu 621 6 throughput throughput NN cord-014597-66vd2mdu 621 7 screening screening NN cord-014597-66vd2mdu 621 8 for for IN cord-014597-66vd2mdu 621 9 perfusion perfusion NN cord-014597-66vd2mdu 621 10 Background Background NNP cord-014597-66vd2mdu 621 11 Perfusion perfusion NN cord-014597-66vd2mdu 621 12 systems system NNS cord-014597-66vd2mdu 621 13 for for IN cord-014597-66vd2mdu 621 14 suspended suspend VBN cord-014597-66vd2mdu 621 15 mammalian mammalian JJ cord-014597-66vd2mdu 621 16 cells cell NNS cord-014597-66vd2mdu 621 17 raise raise VBP cord-014597-66vd2mdu 621 18 growing grow VBG cord-014597-66vd2mdu 621 19 interest interest NN cord-014597-66vd2mdu 621 20 in in IN cord-014597-66vd2mdu 621 21 the the DT cord-014597-66vd2mdu 621 22 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 621 23 industry industry NN cord-014597-66vd2mdu 621 24 . . . cord-014597-66vd2mdu 622 1 Continuous continuous JJ cord-014597-66vd2mdu 622 2 manufacturing manufacturing NN cord-014597-66vd2mdu 622 3 is be VBZ cord-014597-66vd2mdu 622 4 growing grow VBG cord-014597-66vd2mdu 622 5 in in IN cord-014597-66vd2mdu 622 6 the the DT cord-014597-66vd2mdu 622 7 field field NN cord-014597-66vd2mdu 622 8 and and CC cord-014597-66vd2mdu 622 9 is be VBZ cord-014597-66vd2mdu 622 10 encouraged encourage VBN cord-014597-66vd2mdu 622 11 by by IN cord-014597-66vd2mdu 622 12 health health NN cord-014597-66vd2mdu 622 13 authorities authority NNS cord-014597-66vd2mdu 622 14 [ [ -LRB- cord-014597-66vd2mdu 622 15 1 1 CD cord-014597-66vd2mdu 622 16 , , , cord-014597-66vd2mdu 622 17 2 2 CD cord-014597-66vd2mdu 622 18 , , , cord-014597-66vd2mdu 622 19 3 3 CD cord-014597-66vd2mdu 622 20 ] ] -RRB- cord-014597-66vd2mdu 622 21 . . . cord-014597-66vd2mdu 623 1 This this DT cord-014597-66vd2mdu 623 2 work work NN cord-014597-66vd2mdu 623 3 addresses address VBZ cord-014597-66vd2mdu 623 4 scale scale VBP cord-014597-66vd2mdu 623 5 down down RP cord-014597-66vd2mdu 623 6 limitations limitation NNS cord-014597-66vd2mdu 623 7 inherent inherent JJ cord-014597-66vd2mdu 623 8 to to IN cord-014597-66vd2mdu 623 9 continuous continuous JJ cord-014597-66vd2mdu 623 10 media medium NNS cord-014597-66vd2mdu 623 11 exchange exchange NN cord-014597-66vd2mdu 623 12 and and CC cord-014597-66vd2mdu 623 13 cell cell NN cord-014597-66vd2mdu 623 14 retention retention NN cord-014597-66vd2mdu 623 15 by by IN cord-014597-66vd2mdu 623 16 using use VBG cord-014597-66vd2mdu 623 17 a a DT cord-014597-66vd2mdu 623 18 semi semi JJ cord-014597-66vd2mdu 623 19 - - JJ cord-014597-66vd2mdu 623 20 continuous continuous JJ cord-014597-66vd2mdu 623 21 system system NN cord-014597-66vd2mdu 623 22 . . . cord-014597-66vd2mdu 624 1 Data datum NNS cord-014597-66vd2mdu 624 2 was be VBD cord-014597-66vd2mdu 624 3 generated generate VBN cord-014597-66vd2mdu 624 4 with with IN cord-014597-66vd2mdu 624 5 a a DT cord-014597-66vd2mdu 624 6 set set NN cord-014597-66vd2mdu 624 7 of of IN cord-014597-66vd2mdu 624 8 different different JJ cord-014597-66vd2mdu 624 9 clones clone NNS cord-014597-66vd2mdu 624 10 that that WDT cord-014597-66vd2mdu 624 11 were be VBD cord-014597-66vd2mdu 624 12 previously previously RB cord-014597-66vd2mdu 624 13 studied study VBN cord-014597-66vd2mdu 624 14 in in IN cord-014597-66vd2mdu 624 15 fed fed JJ cord-014597-66vd2mdu 624 16 - - HYPH cord-014597-66vd2mdu 624 17 batch batch NN cord-014597-66vd2mdu 624 18 mode mode NN cord-014597-66vd2mdu 624 19 [ [ -LRB- cord-014597-66vd2mdu 624 20 4 4 CD cord-014597-66vd2mdu 624 21 ] ] -RRB- cord-014597-66vd2mdu 624 22 . . . cord-014597-66vd2mdu 625 1 Materials material NNS cord-014597-66vd2mdu 625 2 and and CC cord-014597-66vd2mdu 625 3 methods method NNS cord-014597-66vd2mdu 625 4 4 4 CD cord-014597-66vd2mdu 625 5 CHO CHO NNP cord-014597-66vd2mdu 625 6 - - HYPH cord-014597-66vd2mdu 625 7 K1 K1 NNP cord-014597-66vd2mdu 625 8 cell cell NN cord-014597-66vd2mdu 625 9 lines line NNS cord-014597-66vd2mdu 625 10 expressing express VBG cord-014597-66vd2mdu 625 11 the the DT cord-014597-66vd2mdu 625 12 same same JJ cord-014597-66vd2mdu 625 13 monoclonal monoclonal JJ cord-014597-66vd2mdu 625 14 antibody antibody NN cord-014597-66vd2mdu 625 15 ( ( -LRB- cord-014597-66vd2mdu 625 16 mAb mAb NNS cord-014597-66vd2mdu 625 17 ) ) -RRB- cord-014597-66vd2mdu 625 18 and and CC cord-014597-66vd2mdu 625 19 issued issue VBN cord-014597-66vd2mdu 625 20 from from IN cord-014597-66vd2mdu 625 21 the the DT cord-014597-66vd2mdu 625 22 same same JJ cord-014597-66vd2mdu 625 23 transfection transfection NN cord-014597-66vd2mdu 625 24 were be VBD cord-014597-66vd2mdu 625 25 used use VBN cord-014597-66vd2mdu 625 26 as as IN cord-014597-66vd2mdu 625 27 models model NNS cord-014597-66vd2mdu 625 28 . . . cord-014597-66vd2mdu 626 1 3.5L 3.5L NNS cord-014597-66vd2mdu 626 2 bioreactors bioreactor NNS cord-014597-66vd2mdu 626 3 ( ( -LRB- cord-014597-66vd2mdu 626 4 Sartorius Sartorius NNP cord-014597-66vd2mdu 626 5 ) ) -RRB- cord-014597-66vd2mdu 626 6 were be VBD cord-014597-66vd2mdu 626 7 used use VBN cord-014597-66vd2mdu 626 8 for for IN cord-014597-66vd2mdu 626 9 fed fed NN cord-014597-66vd2mdu 626 10 - - HYPH cord-014597-66vd2mdu 626 11 batch batch NN cord-014597-66vd2mdu 626 12 and and CC cord-014597-66vd2mdu 626 13 perfusion perfusion NN cord-014597-66vd2mdu 626 14 production production NN cord-014597-66vd2mdu 626 15 runs run NNS cord-014597-66vd2mdu 626 16 . . . cord-014597-66vd2mdu 627 1 The the DT cord-014597-66vd2mdu 627 2 perfusion perfusion NN cord-014597-66vd2mdu 627 3 bioreactors bioreactor NNS cord-014597-66vd2mdu 627 4 were be VBD cord-014597-66vd2mdu 627 5 run run VBN cord-014597-66vd2mdu 627 6 using use VBG cord-014597-66vd2mdu 627 7 an an DT cord-014597-66vd2mdu 627 8 alternating alternate VBG cord-014597-66vd2mdu 627 9 tangential tangential JJ cord-014597-66vd2mdu 627 10 flow flow NN cord-014597-66vd2mdu 627 11 filtration filtration NN cord-014597-66vd2mdu 627 12 device device NN cord-014597-66vd2mdu 627 13 ( ( -LRB- cord-014597-66vd2mdu 627 14 Repligen Repligen NNP cord-014597-66vd2mdu 627 15 , , , cord-014597-66vd2mdu 627 16 XCell XCell NNP cord-014597-66vd2mdu 627 17 ™ ™ NN cord-014597-66vd2mdu 627 18 ATF ATF NNP cord-014597-66vd2mdu 627 19 2 2 CD cord-014597-66vd2mdu 627 20 System System NNP cord-014597-66vd2mdu 627 21 ) ) -RRB- cord-014597-66vd2mdu 627 22 . . . cord-014597-66vd2mdu 628 1 The the DT cord-014597-66vd2mdu 628 2 cell cell NN cord-014597-66vd2mdu 628 3 biomass biomass NN cord-014597-66vd2mdu 628 4 was be VBD cord-014597-66vd2mdu 628 5 controlled control VBN cord-014597-66vd2mdu 628 6 by by IN cord-014597-66vd2mdu 628 7 removing remove VBG cord-014597-66vd2mdu 628 8 cells cell NNS cord-014597-66vd2mdu 628 9 through through IN cord-014597-66vd2mdu 628 10 a a DT cord-014597-66vd2mdu 628 11 bleed bleed NN cord-014597-66vd2mdu 628 12 line line NN cord-014597-66vd2mdu 628 13 and and CC cord-014597-66vd2mdu 628 14 was be VBD cord-014597-66vd2mdu 628 15 controlled control VBN cord-014597-66vd2mdu 628 16 using use VBG cord-014597-66vd2mdu 628 17 a a DT cord-014597-66vd2mdu 628 18 biocapacitance biocapacitance NN cord-014597-66vd2mdu 628 19 probe probe NN cord-014597-66vd2mdu 628 20 ( ( -LRB- cord-014597-66vd2mdu 628 21 Hamilton Hamilton NNP cord-014597-66vd2mdu 628 22 , , , cord-014597-66vd2mdu 628 23 Incyte Incyte NNP cord-014597-66vd2mdu 628 24 ) ) -RRB- cord-014597-66vd2mdu 628 25 . . . cord-014597-66vd2mdu 629 1 The the DT cord-014597-66vd2mdu 629 2 perfusion perfusion NN cord-014597-66vd2mdu 629 3 rate rate NN cord-014597-66vd2mdu 629 4 ( ( -LRB- cord-014597-66vd2mdu 629 5 D d NN cord-014597-66vd2mdu 629 6 ) ) -RRB- cord-014597-66vd2mdu 629 7 was be VBD cord-014597-66vd2mdu 629 8 fixed fix VBN cord-014597-66vd2mdu 629 9 to to IN cord-014597-66vd2mdu 629 10 one one CD cord-014597-66vd2mdu 629 11 vessel vessel NN cord-014597-66vd2mdu 629 12 volume volume NN cord-014597-66vd2mdu 629 13 a a DT cord-014597-66vd2mdu 629 14 day day NN cord-014597-66vd2mdu 629 15 ( ( -LRB- cord-014597-66vd2mdu 629 16 vvd vvd NNP cord-014597-66vd2mdu 629 17 -1 -1 NNP cord-014597-66vd2mdu 629 18 ) ) -RRB- cord-014597-66vd2mdu 629 19 . . . cord-014597-66vd2mdu 630 1 The the DT cord-014597-66vd2mdu 630 2 semi semi JJ cord-014597-66vd2mdu 630 3 - - JJ cord-014597-66vd2mdu 630 4 continuous continuous JJ cord-014597-66vd2mdu 630 5 runs run NNS cord-014597-66vd2mdu 630 6 were be VBD cord-014597-66vd2mdu 630 7 made make VBN cord-014597-66vd2mdu 630 8 in in IN cord-014597-66vd2mdu 630 9 50 50 CD cord-014597-66vd2mdu 630 10 mL ml NN cord-014597-66vd2mdu 630 11 shake shake NN cord-014597-66vd2mdu 630 12 tube tube NN cord-014597-66vd2mdu 630 13 ( ( -LRB- cord-014597-66vd2mdu 630 14 TPP TPP NNP cord-014597-66vd2mdu 630 15 , , , cord-014597-66vd2mdu 630 16 TubeSpin TubeSpin NNP cord-014597-66vd2mdu 630 17 ® ® , cord-014597-66vd2mdu 630 18 Bioreactor Bioreactor NNP cord-014597-66vd2mdu 630 19 50 50 CD cord-014597-66vd2mdu 630 20 ) ) -RRB- cord-014597-66vd2mdu 630 21 . . . cord-014597-66vd2mdu 631 1 Once once RB cord-014597-66vd2mdu 631 2 a a DT cord-014597-66vd2mdu 631 3 day day NN cord-014597-66vd2mdu 631 4 , , , cord-014597-66vd2mdu 631 5 the the DT cord-014597-66vd2mdu 631 6 tubes tube NNS cord-014597-66vd2mdu 631 7 were be VBD cord-014597-66vd2mdu 631 8 centrifuged centrifuge VBN cord-014597-66vd2mdu 631 9 ( ( -LRB- cord-014597-66vd2mdu 631 10 5 5 CD cord-014597-66vd2mdu 631 11 min min NN cord-014597-66vd2mdu 631 12 , , , cord-014597-66vd2mdu 631 13 200 200 CD cord-014597-66vd2mdu 631 14 g g NN cord-014597-66vd2mdu 631 15 ) ) -RRB- cord-014597-66vd2mdu 631 16 , , , cord-014597-66vd2mdu 631 17 the the DT cord-014597-66vd2mdu 631 18 supernatant supernatant NN cord-014597-66vd2mdu 631 19 removed remove VBN cord-014597-66vd2mdu 631 20 ( ( -LRB- cord-014597-66vd2mdu 631 21 to to TO cord-014597-66vd2mdu 631 22 mimic mimic VB cord-014597-66vd2mdu 631 23 a a DT cord-014597-66vd2mdu 631 24 perfusion perfusion NN cord-014597-66vd2mdu 631 25 rate rate NN cord-014597-66vd2mdu 631 26 of of IN cord-014597-66vd2mdu 631 27 1 1 CD cord-014597-66vd2mdu 631 28 vvd vvd NNP cord-014597-66vd2mdu 631 29 -1 -1 NNP cord-014597-66vd2mdu 631 30 ) ) -RRB- cord-014597-66vd2mdu 631 31 , , , cord-014597-66vd2mdu 631 32 replaced replace VBN cord-014597-66vd2mdu 631 33 with with IN cord-014597-66vd2mdu 631 34 fresh fresh JJ cord-014597-66vd2mdu 631 35 media medium NNS cord-014597-66vd2mdu 631 36 and and CC cord-014597-66vd2mdu 631 37 cells cell NNS cord-014597-66vd2mdu 631 38 were be VBD cord-014597-66vd2mdu 631 39 re re VBN cord-014597-66vd2mdu 631 40 - - VBN cord-014597-66vd2mdu 631 41 suspended suspend VBN cord-014597-66vd2mdu 631 42 . . . cord-014597-66vd2mdu 632 1 The the DT cord-014597-66vd2mdu 632 2 clone clone NN cord-014597-66vd2mdu 632 3 's 's POS cord-014597-66vd2mdu 632 4 growth growth NN cord-014597-66vd2mdu 632 5 potential potential NN cord-014597-66vd2mdu 632 6 were be VBD cord-014597-66vd2mdu 632 7 preserved preserve VBN cord-014597-66vd2mdu 632 8 across across IN cord-014597-66vd2mdu 632 9 the the DT cord-014597-66vd2mdu 632 10 systems system NNS cord-014597-66vd2mdu 632 11 ( ( -LRB- cord-014597-66vd2mdu 632 12 Fig Fig NNP cord-014597-66vd2mdu 632 13 . . NNP cord-014597-66vd2mdu 632 14 1 1 CD cord-014597-66vd2mdu 632 15 ) ) -RRB- cord-014597-66vd2mdu 632 16 . . . cord-014597-66vd2mdu 633 1 Clone clone NN cord-014597-66vd2mdu 633 2 # # NN cord-014597-66vd2mdu 633 3 3 3 CD cord-014597-66vd2mdu 633 4 always always RB cord-014597-66vd2mdu 633 5 reached reach VBD cord-014597-66vd2mdu 633 6 the the DT cord-014597-66vd2mdu 633 7 highest high JJS cord-014597-66vd2mdu 633 8 viable viable JJ cord-014597-66vd2mdu 633 9 cell cell NN cord-014597-66vd2mdu 633 10 density density NN cord-014597-66vd2mdu 633 11 ( ( -LRB- cord-014597-66vd2mdu 633 12 VCD VCD NNP cord-014597-66vd2mdu 633 13 ) ) -RRB- cord-014597-66vd2mdu 633 14 , , , cord-014597-66vd2mdu 633 15 followed follow VBN cord-014597-66vd2mdu 633 16 by by IN cord-014597-66vd2mdu 633 17 clone clone NN cord-014597-66vd2mdu 633 18 # # $ cord-014597-66vd2mdu 633 19 1 1 CD cord-014597-66vd2mdu 633 20 . . . cord-014597-66vd2mdu 634 1 Clone clone NN cord-014597-66vd2mdu 634 2 # # $ cord-014597-66vd2mdu 634 3 2 2 CD cord-014597-66vd2mdu 634 4 and and CC cord-014597-66vd2mdu 634 5 # # $ cord-014597-66vd2mdu 634 6 4 4 CD cord-014597-66vd2mdu 634 7 showed show VBD cord-014597-66vd2mdu 634 8 similar similar JJ cord-014597-66vd2mdu 634 9 growth growth NN cord-014597-66vd2mdu 634 10 characteristics characteristic NNS cord-014597-66vd2mdu 634 11 . . . cord-014597-66vd2mdu 635 1 It -PRON- PRP cord-014597-66vd2mdu 635 2 is be VBZ cord-014597-66vd2mdu 635 3 interesting interesting JJ cord-014597-66vd2mdu 635 4 to to TO cord-014597-66vd2mdu 635 5 note note VB cord-014597-66vd2mdu 635 6 that that IN cord-014597-66vd2mdu 635 7 in in IN cord-014597-66vd2mdu 635 8 the the DT cord-014597-66vd2mdu 635 9 perfusion perfusion NN cord-014597-66vd2mdu 635 10 bioreactor bioreactor NN cord-014597-66vd2mdu 635 11 different different JJ cord-014597-66vd2mdu 635 12 patterns pattern NNS cord-014597-66vd2mdu 635 13 in in IN cord-014597-66vd2mdu 635 14 terms term NNS cord-014597-66vd2mdu 635 15 of of IN cord-014597-66vd2mdu 635 16 VCD vcd NN cord-014597-66vd2mdu 635 17 were be VBD cord-014597-66vd2mdu 635 18 observed observe VBN cord-014597-66vd2mdu 635 19 although although IN cord-014597-66vd2mdu 635 20 the the DT cord-014597-66vd2mdu 635 21 cell cell NN cord-014597-66vd2mdu 635 22 biomass biomass NN cord-014597-66vd2mdu 635 23 signals signal NNS cord-014597-66vd2mdu 635 24 were be VBD cord-014597-66vd2mdu 635 25 similar similar JJ cord-014597-66vd2mdu 635 26 for for IN cord-014597-66vd2mdu 635 27 all all DT cord-014597-66vd2mdu 635 28 4 4 CD cord-014597-66vd2mdu 635 29 runs run NNS cord-014597-66vd2mdu 635 30 . . . cord-014597-66vd2mdu 636 1 This this DT cord-014597-66vd2mdu 636 2 reflects reflect VBZ cord-014597-66vd2mdu 636 3 the the DT cord-014597-66vd2mdu 636 4 fact fact NN cord-014597-66vd2mdu 636 5 that that IN cord-014597-66vd2mdu 636 6 the the DT cord-014597-66vd2mdu 636 7 capacitance capacitance NN cord-014597-66vd2mdu 636 8 measures measure VBZ cord-014597-66vd2mdu 636 9 the the DT cord-014597-66vd2mdu 636 10 biomass biomass NN cord-014597-66vd2mdu 636 11 and and CC cord-014597-66vd2mdu 636 12 not not RB cord-014597-66vd2mdu 636 13 the the DT cord-014597-66vd2mdu 636 14 absolute absolute JJ cord-014597-66vd2mdu 636 15 cell cell NN cord-014597-66vd2mdu 636 16 count count NN cord-014597-66vd2mdu 636 17 [ [ -LRB- cord-014597-66vd2mdu 636 18 5 5 CD cord-014597-66vd2mdu 636 19 ] ] -RRB- cord-014597-66vd2mdu 636 20 . . . cord-014597-66vd2mdu 637 1 To to TO cord-014597-66vd2mdu 637 2 estimate estimate VB cord-014597-66vd2mdu 637 3 the the DT cord-014597-66vd2mdu 637 4 minimum minimum JJ cord-014597-66vd2mdu 637 5 cell cell NN cord-014597-66vd2mdu 637 6 specific specific JJ cord-014597-66vd2mdu 637 7 perfusion perfusion NN cord-014597-66vd2mdu 637 8 rate rate NN cord-014597-66vd2mdu 637 9 ( ( -LRB- cord-014597-66vd2mdu 637 10 CSPR CSPR NNP cord-014597-66vd2mdu 637 11 min min NNP cord-014597-66vd2mdu 637 12 ) ) -RRB- cord-014597-66vd2mdu 637 13 in in IN cord-014597-66vd2mdu 637 14 the the DT cord-014597-66vd2mdu 637 15 semi semi JJ cord-014597-66vd2mdu 637 16 - - JJ cord-014597-66vd2mdu 637 17 continuous continuous JJ cord-014597-66vd2mdu 637 18 experiment experiment NN cord-014597-66vd2mdu 637 19 , , , cord-014597-66vd2mdu 637 20 the the DT cord-014597-66vd2mdu 637 21 perfusion perfusion NN cord-014597-66vd2mdu 637 22 rate rate NN cord-014597-66vd2mdu 637 23 was be VBD cord-014597-66vd2mdu 637 24 divided divide VBN cord-014597-66vd2mdu 637 25 by by IN cord-014597-66vd2mdu 637 26 the the DT cord-014597-66vd2mdu 637 27 maximum maximum JJ cord-014597-66vd2mdu 637 28 viable viable JJ cord-014597-66vd2mdu 637 29 cell cell NN cord-014597-66vd2mdu 637 30 density density NN cord-014597-66vd2mdu 637 31 ( ( -LRB- cord-014597-66vd2mdu 637 32 VCD VCD NNP cord-014597-66vd2mdu 637 33 max max NNP cord-014597-66vd2mdu 637 34 ) ) -RRB- cord-014597-66vd2mdu 637 35 . . . cord-014597-66vd2mdu 638 1 This this DT cord-014597-66vd2mdu 638 2 value value NN cord-014597-66vd2mdu 638 3 was be VBD cord-014597-66vd2mdu 638 4 compared compare VBN cord-014597-66vd2mdu 638 5 to to IN cord-014597-66vd2mdu 638 6 the the DT cord-014597-66vd2mdu 638 7 CSPR CSPR NNP cord-014597-66vd2mdu 638 8 obtained obtain VBD cord-014597-66vd2mdu 638 9 during during IN cord-014597-66vd2mdu 638 10 the the DT cord-014597-66vd2mdu 638 11 4 4 CD cord-014597-66vd2mdu 638 12 th th XX cord-014597-66vd2mdu 638 13 set set NN cord-014597-66vd2mdu 638 14 - - HYPH cord-014597-66vd2mdu 638 15 point point NN cord-014597-66vd2mdu 638 16 ( ( -LRB- cord-014597-66vd2mdu 638 17 SP4 SP4 NNP cord-014597-66vd2mdu 638 18 ) ) -RRB- cord-014597-66vd2mdu 638 19 of of IN cord-014597-66vd2mdu 638 20 the the DT cord-014597-66vd2mdu 638 21 perfusion perfusion NN cord-014597-66vd2mdu 638 22 runs run NNS cord-014597-66vd2mdu 638 23 . . . cord-014597-66vd2mdu 639 1 As as IN cord-014597-66vd2mdu 639 2 expected expect VBN cord-014597-66vd2mdu 639 3 , , , cord-014597-66vd2mdu 639 4 the the DT cord-014597-66vd2mdu 639 5 bleed bleed NN cord-014597-66vd2mdu 639 6 fraction fraction NN cord-014597-66vd2mdu 639 7 decreased decrease VBD cord-014597-66vd2mdu 639 8 when when WRB cord-014597-66vd2mdu 639 9 the the DT cord-014597-66vd2mdu 639 10 capacitance capacitance NN cord-014597-66vd2mdu 639 11 set set NN cord-014597-66vd2mdu 639 12 - - HYPH cord-014597-66vd2mdu 639 13 point point NN cord-014597-66vd2mdu 639 14 was be VBD cord-014597-66vd2mdu 639 15 increased increase VBN cord-014597-66vd2mdu 639 16 and and CC cord-014597-66vd2mdu 639 17 went go VBD cord-014597-66vd2mdu 639 18 down down RB cord-014597-66vd2mdu 639 19 to to IN cord-014597-66vd2mdu 639 20 5 5 CD cord-014597-66vd2mdu 639 21 % % NN cord-014597-66vd2mdu 639 22 or or CC cord-014597-66vd2mdu 639 23 less less JJR cord-014597-66vd2mdu 639 24 of of IN cord-014597-66vd2mdu 639 25 the the DT cord-014597-66vd2mdu 639 26 total total JJ cord-014597-66vd2mdu 639 27 perfusion perfusion NN cord-014597-66vd2mdu 639 28 rate rate NN cord-014597-66vd2mdu 639 29 ( ( -LRB- cord-014597-66vd2mdu 639 30 data datum NNS cord-014597-66vd2mdu 639 31 not not RB cord-014597-66vd2mdu 639 32 shown show VBN cord-014597-66vd2mdu 639 33 ) ) -RRB- cord-014597-66vd2mdu 639 34 . . . cord-014597-66vd2mdu 640 1 Since since IN cord-014597-66vd2mdu 640 2 the the DT cord-014597-66vd2mdu 640 3 bleed bleed NN cord-014597-66vd2mdu 640 4 removes remove VBZ cord-014597-66vd2mdu 640 5 the the DT cord-014597-66vd2mdu 640 6 excess excess JJ cord-014597-66vd2mdu 640 7 biomass biomass NN cord-014597-66vd2mdu 640 8 , , , cord-014597-66vd2mdu 640 9 it -PRON- PRP cord-014597-66vd2mdu 640 10 is be VBZ cord-014597-66vd2mdu 640 11 an an DT cord-014597-66vd2mdu 640 12 indication indication NN cord-014597-66vd2mdu 640 13 of of IN cord-014597-66vd2mdu 640 14 how how WRB cord-014597-66vd2mdu 640 15 close close JJ cord-014597-66vd2mdu 640 16 to to IN cord-014597-66vd2mdu 640 17 a a DT cord-014597-66vd2mdu 640 18 limitation limitation NN cord-014597-66vd2mdu 640 19 the the DT cord-014597-66vd2mdu 640 20 system system NN cord-014597-66vd2mdu 640 21 is be VBZ cord-014597-66vd2mdu 640 22 . . . cord-014597-66vd2mdu 641 1 Therefore therefore RB cord-014597-66vd2mdu 641 2 , , , cord-014597-66vd2mdu 641 3 the the DT cord-014597-66vd2mdu 641 4 CSPR CSPR NNP cord-014597-66vd2mdu 641 5 calculated calculate VBN cord-014597-66vd2mdu 641 6 at at IN cord-014597-66vd2mdu 641 7 SP4 SP4 NNP cord-014597-66vd2mdu 641 8 was be VBD cord-014597-66vd2mdu 641 9 considered consider VBN cord-014597-66vd2mdu 641 10 as as IN cord-014597-66vd2mdu 641 11 the the DT cord-014597-66vd2mdu 641 12 minimum minimum JJ cord-014597-66vd2mdu 641 13 CSPR CSPR NNP cord-014597-66vd2mdu 641 14 . . . cord-014597-66vd2mdu 642 1 The the DT cord-014597-66vd2mdu 642 2 CSPR CSPR NNP cord-014597-66vd2mdu 642 3 min min NN cord-014597-66vd2mdu 642 4 obtained obtain VBD cord-014597-66vd2mdu 642 5 in in IN cord-014597-66vd2mdu 642 6 both both DT cord-014597-66vd2mdu 642 7 systems system NNS cord-014597-66vd2mdu 642 8 were be VBD cord-014597-66vd2mdu 642 9 very very RB cord-014597-66vd2mdu 642 10 close close JJ cord-014597-66vd2mdu 642 11 ( ( -LRB- cord-014597-66vd2mdu 642 12 Table table NN cord-014597-66vd2mdu 642 13 1 1 CD cord-014597-66vd2mdu 642 14 ) ) -RRB- cord-014597-66vd2mdu 642 15 . . . cord-014597-66vd2mdu 643 1 The the DT cord-014597-66vd2mdu 643 2 semi semi JJ cord-014597-66vd2mdu 643 3 - - JJ cord-014597-66vd2mdu 643 4 continuous continuous JJ cord-014597-66vd2mdu 643 5 system system NN cord-014597-66vd2mdu 643 6 can can MD cord-014597-66vd2mdu 643 7 therefore therefore RB cord-014597-66vd2mdu 643 8 be be VB cord-014597-66vd2mdu 643 9 used use VBN cord-014597-66vd2mdu 643 10 to to TO cord-014597-66vd2mdu 643 11 identify identify VB cord-014597-66vd2mdu 643 12 the the DT cord-014597-66vd2mdu 643 13 CSPR CSPR NNP cord-014597-66vd2mdu 643 14 min min NNP cord-014597-66vd2mdu 643 15 before before IN cord-014597-66vd2mdu 643 16 running run VBG cord-014597-66vd2mdu 643 17 a a DT cord-014597-66vd2mdu 643 18 continuous continuous JJ cord-014597-66vd2mdu 643 19 bioreactor bioreactor NN cord-014597-66vd2mdu 643 20 , , , cord-014597-66vd2mdu 643 21 it -PRON- PRP cord-014597-66vd2mdu 643 22 therefore therefore RB cord-014597-66vd2mdu 643 23 facilitates facilitate VBZ cord-014597-66vd2mdu 643 24 the the DT cord-014597-66vd2mdu 643 25 decision decision NN cord-014597-66vd2mdu 643 26 making make VBG cord-014597-66vd2mdu 643 27 early early RB cord-014597-66vd2mdu 643 28 in in IN cord-014597-66vd2mdu 643 29 the the DT cord-014597-66vd2mdu 643 30 development development NN cord-014597-66vd2mdu 643 31 ( ( -LRB- cord-014597-66vd2mdu 643 32 to to TO cord-014597-66vd2mdu 643 33 define define VB cord-014597-66vd2mdu 643 34 the the DT cord-014597-66vd2mdu 643 35 target target NN cord-014597-66vd2mdu 643 36 cell cell NN cord-014597-66vd2mdu 643 37 density density NN cord-014597-66vd2mdu 643 38 for for IN cord-014597-66vd2mdu 643 39 a a DT cord-014597-66vd2mdu 643 40 defined define VBN cord-014597-66vd2mdu 643 41 perfusion perfusion NN cord-014597-66vd2mdu 643 42 rate rate NN cord-014597-66vd2mdu 643 43 ) ) -RRB- cord-014597-66vd2mdu 643 44 . . . cord-014597-66vd2mdu 644 1 The the DT cord-014597-66vd2mdu 644 2 specific specific JJ cord-014597-66vd2mdu 644 3 productivity productivity NN cord-014597-66vd2mdu 644 4 ( ( -LRB- cord-014597-66vd2mdu 644 5 Q q NN cord-014597-66vd2mdu 644 6 p p NN cord-014597-66vd2mdu 644 7 ) ) -RRB- cord-014597-66vd2mdu 644 8 of of IN cord-014597-66vd2mdu 644 9 the the DT cord-014597-66vd2mdu 644 10 4 4 CD cord-014597-66vd2mdu 644 11 clones clone NNS cord-014597-66vd2mdu 644 12 was be VBD cord-014597-66vd2mdu 644 13 quantified quantify VBN cord-014597-66vd2mdu 644 14 at at IN cord-014597-66vd2mdu 644 15 the the DT cord-014597-66vd2mdu 644 16 maximum maximum JJ cord-014597-66vd2mdu 644 17 VCD vcd NN cord-014597-66vd2mdu 644 18 ( ( -LRB- cord-014597-66vd2mdu 644 19 semi semi JJ cord-014597-66vd2mdu 644 20 - - JJ cord-014597-66vd2mdu 644 21 continuous continuous JJ cord-014597-66vd2mdu 644 22 ) ) -RRB- cord-014597-66vd2mdu 644 23 or or CC cord-014597-66vd2mdu 644 24 at at IN cord-014597-66vd2mdu 644 25 SP4 SP4 NNP cord-014597-66vd2mdu 644 26 ( ( -LRB- cord-014597-66vd2mdu 644 27 perfusion perfusion NN cord-014597-66vd2mdu 644 28 ) ) -RRB- cord-014597-66vd2mdu 644 29 . . . cord-014597-66vd2mdu 645 1 Absolute absolute JJ cord-014597-66vd2mdu 645 2 values value NNS cord-014597-66vd2mdu 645 3 are be VBP cord-014597-66vd2mdu 645 4 not not RB cord-014597-66vd2mdu 645 5 representative representative JJ cord-014597-66vd2mdu 645 6 since since IN cord-014597-66vd2mdu 645 7 the the DT cord-014597-66vd2mdu 645 8 cell cell NN cord-014597-66vd2mdu 645 9 environment environment NN cord-014597-66vd2mdu 645 10 is be VBZ cord-014597-66vd2mdu 645 11 so so RB cord-014597-66vd2mdu 645 12 different different JJ cord-014597-66vd2mdu 645 13 in in IN cord-014597-66vd2mdu 645 14 both both DT cord-014597-66vd2mdu 645 15 systems system NNS cord-014597-66vd2mdu 645 16 . . . cord-014597-66vd2mdu 646 1 Nevertheless nevertheless RB cord-014597-66vd2mdu 646 2 , , , cord-014597-66vd2mdu 646 3 a a DT cord-014597-66vd2mdu 646 4 relative relative JJ cord-014597-66vd2mdu 646 5 ranking ranking NN cord-014597-66vd2mdu 646 6 proved prove VBD cord-014597-66vd2mdu 646 7 to to TO cord-014597-66vd2mdu 646 8 be be VB cord-014597-66vd2mdu 646 9 indicative indicative JJ cord-014597-66vd2mdu 646 10 of of IN cord-014597-66vd2mdu 646 11 the the DT cord-014597-66vd2mdu 646 12 respective respective JJ cord-014597-66vd2mdu 646 13 performances performance NNS cord-014597-66vd2mdu 646 14 ( ( -LRB- cord-014597-66vd2mdu 646 15 Table table NN cord-014597-66vd2mdu 646 16 1 1 CD cord-014597-66vd2mdu 646 17 ) ) -RRB- cord-014597-66vd2mdu 646 18 . . . cord-014597-66vd2mdu 647 1 The the DT cord-014597-66vd2mdu 647 2 maximum maximum JJ cord-014597-66vd2mdu 647 3 cell cell NN cord-014597-66vd2mdu 647 4 growth growth NN cord-014597-66vd2mdu 647 5 in in IN cord-014597-66vd2mdu 647 6 fed fed NNP cord-014597-66vd2mdu 647 7 - - HYPH cord-014597-66vd2mdu 647 8 batch batch NN cord-014597-66vd2mdu 647 9 , , , cord-014597-66vd2mdu 647 10 semi semi JJ cord-014597-66vd2mdu 647 11 - - JJ cord-014597-66vd2mdu 647 12 continuous continuous JJ cord-014597-66vd2mdu 647 13 and and CC cord-014597-66vd2mdu 647 14 perfusion perfusion NN cord-014597-66vd2mdu 647 15 were be VBD cord-014597-66vd2mdu 647 16 also also RB cord-014597-66vd2mdu 647 17 compared compare VBN cord-014597-66vd2mdu 647 18 , , , cord-014597-66vd2mdu 647 19 their -PRON- PRP$ cord-014597-66vd2mdu 647 20 ranking ranking NN cord-014597-66vd2mdu 647 21 was be VBD cord-014597-66vd2mdu 647 22 always always RB cord-014597-66vd2mdu 647 23 preserved preserve VBN cord-014597-66vd2mdu 647 24 . . . cord-014597-66vd2mdu 648 1 Both both DT cord-014597-66vd2mdu 648 2 indications indication NNS cord-014597-66vd2mdu 648 3 can can MD cord-014597-66vd2mdu 648 4 be be VB cord-014597-66vd2mdu 648 5 used use VBN cord-014597-66vd2mdu 648 6 to to TO cord-014597-66vd2mdu 648 7 assess assess VB cord-014597-66vd2mdu 648 8 a a DT cord-014597-66vd2mdu 648 9 performance performance NN cord-014597-66vd2mdu 648 10 ranking ranking NN cord-014597-66vd2mdu 648 11 for for IN cord-014597-66vd2mdu 648 12 different different JJ cord-014597-66vd2mdu 648 13 clones clone NNS cord-014597-66vd2mdu 648 14 . . . cord-014597-66vd2mdu 649 1 The the DT cord-014597-66vd2mdu 649 2 performance performance NN cord-014597-66vd2mdu 649 3 of of IN cord-014597-66vd2mdu 649 4 4 4 CD cord-014597-66vd2mdu 649 5 clones clone NNS cord-014597-66vd2mdu 649 6 was be VBD cord-014597-66vd2mdu 649 7 studied study VBN cord-014597-66vd2mdu 649 8 in in IN cord-014597-66vd2mdu 649 9 3 3 CD cord-014597-66vd2mdu 649 10 different different JJ cord-014597-66vd2mdu 649 11 cultivation cultivation NN cord-014597-66vd2mdu 649 12 systems system NNS cord-014597-66vd2mdu 649 13 : : : cord-014597-66vd2mdu 649 14 fed feed VBN cord-014597-66vd2mdu 649 15 - - HYPH cord-014597-66vd2mdu 649 16 batch batch NN cord-014597-66vd2mdu 649 17 / / SYM cord-014597-66vd2mdu 649 18 perfusion perfusion NN cord-014597-66vd2mdu 649 19 bioreactors bioreactor NNS cord-014597-66vd2mdu 649 20 and and CC cord-014597-66vd2mdu 649 21 semi semi JJ cord-014597-66vd2mdu 649 22 - - JJ cord-014597-66vd2mdu 649 23 continuous continuous JJ cord-014597-66vd2mdu 649 24 shake shake NN cord-014597-66vd2mdu 649 25 tube tube NN cord-014597-66vd2mdu 649 26 . . . cord-014597-66vd2mdu 650 1 The the DT cord-014597-66vd2mdu 650 2 semi semi JJ cord-014597-66vd2mdu 650 3 - - JJ cord-014597-66vd2mdu 650 4 continuous continuous JJ cord-014597-66vd2mdu 650 5 system system NN cord-014597-66vd2mdu 650 6 was be VBD cord-014597-66vd2mdu 650 7 able able JJ cord-014597-66vd2mdu 650 8 to to TO cord-014597-66vd2mdu 650 9 precisely precisely RB cord-014597-66vd2mdu 650 10 predict predict VB cord-014597-66vd2mdu 650 11 the the DT cord-014597-66vd2mdu 650 12 CSPR CSPR NNP cord-014597-66vd2mdu 650 13 min min NNP cord-014597-66vd2mdu 650 14 , , , cord-014597-66vd2mdu 650 15 an an DT cord-014597-66vd2mdu 650 16 important important JJ cord-014597-66vd2mdu 650 17 process process NN cord-014597-66vd2mdu 650 18 parameter parameter NN cord-014597-66vd2mdu 650 19 for for IN cord-014597-66vd2mdu 650 20 perfusion perfusion NN cord-014597-66vd2mdu 650 21 . . . cord-014597-66vd2mdu 651 1 Specific specific JJ cord-014597-66vd2mdu 651 2 productivity productivity NN cord-014597-66vd2mdu 651 3 and and CC cord-014597-66vd2mdu 651 4 maximum maximum JJ cord-014597-66vd2mdu 651 5 cell cell NN cord-014597-66vd2mdu 651 6 density density NN cord-014597-66vd2mdu 651 7 ranking ranking NN cord-014597-66vd2mdu 651 8 was be VBD cord-014597-66vd2mdu 651 9 preserved preserve VBN cord-014597-66vd2mdu 651 10 across across IN cord-014597-66vd2mdu 651 11 the the DT cord-014597-66vd2mdu 651 12 systems system NNS cord-014597-66vd2mdu 651 13 , , , cord-014597-66vd2mdu 651 14 therefore therefore RB cord-014597-66vd2mdu 651 15 the the DT cord-014597-66vd2mdu 651 16 scale scale NN cord-014597-66vd2mdu 651 17 down down RP cord-014597-66vd2mdu 651 18 experiment experiment NN cord-014597-66vd2mdu 651 19 can can MD cord-014597-66vd2mdu 651 20 be be VB cord-014597-66vd2mdu 651 21 used use VBN cord-014597-66vd2mdu 651 22 to to TO cord-014597-66vd2mdu 651 23 assess assess VB cord-014597-66vd2mdu 651 24 a a DT cord-014597-66vd2mdu 651 25 performance performance NN cord-014597-66vd2mdu 651 26 ranking rank VBG cord-014597-66vd2mdu 651 27 for for IN cord-014597-66vd2mdu 651 28 perfusion perfusion NN cord-014597-66vd2mdu 651 29 clone clone NN cord-014597-66vd2mdu 651 30 screening screening NN cord-014597-66vd2mdu 651 31 . . . cord-014597-66vd2mdu 652 1 Modulating modulate VBG cord-014597-66vd2mdu 652 2 antibody antibody NN cord-014597-66vd2mdu 652 3 galactosylation galactosylation NN cord-014597-66vd2mdu 652 4 through through IN cord-014597-66vd2mdu 652 5 cell cell NN cord-014597-66vd2mdu 652 6 culture culture NN cord-014597-66vd2mdu 652 7 medium medium NN cord-014597-66vd2mdu 652 8 for for IN cord-014597-66vd2mdu 652 9 improved improved JJ cord-014597-66vd2mdu 652 10 function function NN cord-014597-66vd2mdu 652 11 and and CC cord-014597-66vd2mdu 652 12 product product NN cord-014597-66vd2mdu 652 13 quality quality NN cord-014597-66vd2mdu 653 1 Jenny Jenny NNP cord-014597-66vd2mdu 653 2 Y. Y. NNP cord-014597-66vd2mdu 653 3 Bang Bang NNP cord-014597-66vd2mdu 653 4 , , , cord-014597-66vd2mdu 653 5 James James NNP cord-014597-66vd2mdu 653 6 - - HYPH cord-014597-66vd2mdu 653 7 Kevin Kevin NNP cord-014597-66vd2mdu 653 8 Y. Y. NNP cord-014597-66vd2mdu 653 9 Tan Tan NNP cord-014597-66vd2mdu 654 1 The the DT cord-014597-66vd2mdu 654 2 production production NN cord-014597-66vd2mdu 654 3 of of IN cord-014597-66vd2mdu 654 4 therapeutic therapeutic JJ cord-014597-66vd2mdu 654 5 antibodies antibody NNS cord-014597-66vd2mdu 654 6 ( ( -LRB- cord-014597-66vd2mdu 654 7 Abs abs NN cord-014597-66vd2mdu 654 8 ) ) -RRB- cord-014597-66vd2mdu 654 9 requires require VBZ cord-014597-66vd2mdu 654 10 high high JJ cord-014597-66vd2mdu 654 11 titers titer NNS cord-014597-66vd2mdu 654 12 and and CC cord-014597-66vd2mdu 654 13 excellent excellent JJ cord-014597-66vd2mdu 654 14 product product NN cord-014597-66vd2mdu 654 15 quality quality NN cord-014597-66vd2mdu 654 16 to to TO cord-014597-66vd2mdu 654 17 ensure ensure VB cord-014597-66vd2mdu 654 18 efficient efficient JJ cord-014597-66vd2mdu 654 19 manufacturing manufacturing NN cord-014597-66vd2mdu 654 20 and and CC cord-014597-66vd2mdu 654 21 potent potent JJ cord-014597-66vd2mdu 654 22 drug drug NN cord-014597-66vd2mdu 654 23 efficacy efficacy NN cord-014597-66vd2mdu 654 24 . . . cord-014597-66vd2mdu 655 1 Glycosylation Glycosylation NNP cord-014597-66vd2mdu 655 2 , , , cord-014597-66vd2mdu 655 3 or or CC cord-014597-66vd2mdu 655 4 the the DT cord-014597-66vd2mdu 655 5 attachment attachment NN cord-014597-66vd2mdu 655 6 of of IN cord-014597-66vd2mdu 655 7 sugars sugar NNS cord-014597-66vd2mdu 655 8 to to IN cord-014597-66vd2mdu 655 9 organic organic JJ cord-014597-66vd2mdu 655 10 molecules molecule NNS cord-014597-66vd2mdu 655 11 , , , cord-014597-66vd2mdu 655 12 is be VBZ cord-014597-66vd2mdu 655 13 a a DT cord-014597-66vd2mdu 655 14 critical critical JJ cord-014597-66vd2mdu 655 15 quality quality NN cord-014597-66vd2mdu 655 16 aspect aspect NN cord-014597-66vd2mdu 655 17 that that WDT cord-014597-66vd2mdu 655 18 can can MD cord-014597-66vd2mdu 655 19 significantly significantly RB cord-014597-66vd2mdu 655 20 alter alter VB cord-014597-66vd2mdu 655 21 Ab Ab NNP cord-014597-66vd2mdu 655 22 binding binding NN cord-014597-66vd2mdu 655 23 , , , cord-014597-66vd2mdu 655 24 function function NN cord-014597-66vd2mdu 655 25 , , , cord-014597-66vd2mdu 655 26 and and CC cord-014597-66vd2mdu 655 27 therapeutic therapeutic JJ cord-014597-66vd2mdu 655 28 effect effect NN cord-014597-66vd2mdu 655 29 [ [ -LRB- cord-014597-66vd2mdu 655 30 1 1 CD cord-014597-66vd2mdu 655 31 ] ] -RRB- cord-014597-66vd2mdu 655 32 . . . cord-014597-66vd2mdu 656 1 Galactose galactose NN cord-014597-66vd2mdu 656 2 is be VBZ cord-014597-66vd2mdu 656 3 a a DT cord-014597-66vd2mdu 656 4 key key JJ cord-014597-66vd2mdu 656 5 sugar sugar NN cord-014597-66vd2mdu 656 6 of of IN cord-014597-66vd2mdu 656 7 interest interest NN cord-014597-66vd2mdu 656 8 due due IN cord-014597-66vd2mdu 656 9 to to IN cord-014597-66vd2mdu 656 10 its -PRON- PRP$ cord-014597-66vd2mdu 656 11 significant significant JJ cord-014597-66vd2mdu 656 12 impact impact NN cord-014597-66vd2mdu 656 13 on on IN cord-014597-66vd2mdu 656 14 Ab Ab NNP cord-014597-66vd2mdu 656 15 function function NN cord-014597-66vd2mdu 656 16 and and CC cord-014597-66vd2mdu 656 17 the the DT cord-014597-66vd2mdu 656 18 ability ability NN cord-014597-66vd2mdu 656 19 to to TO cord-014597-66vd2mdu 656 20 control control VB cord-014597-66vd2mdu 656 21 galactosylation galactosylation NN cord-014597-66vd2mdu 656 22 through through IN cord-014597-66vd2mdu 656 23 cell cell NN cord-014597-66vd2mdu 656 24 culture culture NN cord-014597-66vd2mdu 656 25 medium medium NN cord-014597-66vd2mdu 656 26 . . . cord-014597-66vd2mdu 657 1 Herein herein RB cord-014597-66vd2mdu 657 2 , , , cord-014597-66vd2mdu 657 3 Irvine Irvine NNP cord-014597-66vd2mdu 657 4 Scientific Scientific NNP cord-014597-66vd2mdu 657 5 assessed assess VBD cord-014597-66vd2mdu 657 6 the the DT cord-014597-66vd2mdu 657 7 ability ability NN cord-014597-66vd2mdu 657 8 of of IN cord-014597-66vd2mdu 657 9 media medium NNS cord-014597-66vd2mdu 657 10 components component NNS cord-014597-66vd2mdu 657 11 to to TO cord-014597-66vd2mdu 657 12 modulate modulate VB cord-014597-66vd2mdu 657 13 galactose galactose NN cord-014597-66vd2mdu 657 14 levels level NNS cord-014597-66vd2mdu 657 15 on on IN cord-014597-66vd2mdu 657 16 a a DT cord-014597-66vd2mdu 657 17 model model NN cord-014597-66vd2mdu 657 18 therapeutic therapeutic JJ cord-014597-66vd2mdu 657 19 Ab ab NN cord-014597-66vd2mdu 657 20 . . . cord-014597-66vd2mdu 658 1 Various various JJ cord-014597-66vd2mdu 658 2 media medium NNS cord-014597-66vd2mdu 658 3 compositions composition NNS cord-014597-66vd2mdu 658 4 were be VBD cord-014597-66vd2mdu 658 5 able able JJ cord-014597-66vd2mdu 658 6 to to TO cord-014597-66vd2mdu 658 7 modulate modulate VB cord-014597-66vd2mdu 658 8 galactosylation galactosylation NN cord-014597-66vd2mdu 658 9 levels level NNS cord-014597-66vd2mdu 658 10 without without IN cord-014597-66vd2mdu 658 11 compromising compromise VBG cord-014597-66vd2mdu 658 12 cell cell NN cord-014597-66vd2mdu 658 13 growth growth NN cord-014597-66vd2mdu 658 14 and and CC cord-014597-66vd2mdu 658 15 Ab Ab NNP cord-014597-66vd2mdu 658 16 titers titer NNS cord-014597-66vd2mdu 658 17 . . . cord-014597-66vd2mdu 659 1 In in IN cord-014597-66vd2mdu 659 2 addition addition NN cord-014597-66vd2mdu 659 3 , , , cord-014597-66vd2mdu 659 4 an an DT cord-014597-66vd2mdu 659 5 in in FW cord-014597-66vd2mdu 659 6 vitro vitro FW cord-014597-66vd2mdu 659 7 assay assay NN cord-014597-66vd2mdu 659 8 was be VBD cord-014597-66vd2mdu 659 9 utilized utilize VBN cord-014597-66vd2mdu 659 10 to to TO cord-014597-66vd2mdu 659 11 evaluate evaluate VB cord-014597-66vd2mdu 659 12 the the DT cord-014597-66vd2mdu 659 13 functional functional JJ cord-014597-66vd2mdu 659 14 ability ability NN cord-014597-66vd2mdu 659 15 of of IN cord-014597-66vd2mdu 659 16 Abs abs NN cord-014597-66vd2mdu 659 17 to to TO cord-014597-66vd2mdu 659 18 bind bind VB cord-014597-66vd2mdu 659 19 and and CC cord-014597-66vd2mdu 659 20 activate activate VB cord-014597-66vd2mdu 659 21 complement complement NN cord-014597-66vd2mdu 659 22 - - HYPH cord-014597-66vd2mdu 659 23 dependent dependent JJ cord-014597-66vd2mdu 659 24 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 659 25 ( ( -LRB- cord-014597-66vd2mdu 659 26 CDC CDC NNP cord-014597-66vd2mdu 659 27 ) ) -RRB- cord-014597-66vd2mdu 659 28 . . . cord-014597-66vd2mdu 660 1 Differences difference NNS cord-014597-66vd2mdu 660 2 in in IN cord-014597-66vd2mdu 660 3 galactosylation galactosylation NN cord-014597-66vd2mdu 660 4 significantly significantly RB cord-014597-66vd2mdu 660 5 altered alter VBD cord-014597-66vd2mdu 660 6 the the DT cord-014597-66vd2mdu 660 7 Abs abs NN cord-014597-66vd2mdu 660 8 ' ' POS cord-014597-66vd2mdu 660 9 ability ability NN cord-014597-66vd2mdu 660 10 to to TO cord-014597-66vd2mdu 660 11 induce induce VB cord-014597-66vd2mdu 660 12 cell cell NN cord-014597-66vd2mdu 660 13 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 660 14 . . . cord-014597-66vd2mdu 661 1 Furthermore furthermore RB cord-014597-66vd2mdu 661 2 , , , cord-014597-66vd2mdu 661 3 design design NN cord-014597-66vd2mdu 661 4 of of IN cord-014597-66vd2mdu 661 5 experiment experiment NN cord-014597-66vd2mdu 661 6 analysis analysis NN cord-014597-66vd2mdu 661 7 determined determine VBD cord-014597-66vd2mdu 661 8 the the DT cord-014597-66vd2mdu 661 9 optimal optimal JJ cord-014597-66vd2mdu 661 10 ratio ratio NN cord-014597-66vd2mdu 661 11 of of IN cord-014597-66vd2mdu 661 12 supplements supplement NNS cord-014597-66vd2mdu 661 13 to to TO cord-014597-66vd2mdu 661 14 maximize maximize VB cord-014597-66vd2mdu 661 15 galactosylation galactosylation NN cord-014597-66vd2mdu 661 16 . . . cord-014597-66vd2mdu 662 1 This this DT cord-014597-66vd2mdu 662 2 " " `` cord-014597-66vd2mdu 662 3 Optimized optimize VBN cord-014597-66vd2mdu 662 4 Supplement supplement NN cord-014597-66vd2mdu 662 5 " " '' cord-014597-66vd2mdu 662 6 was be VBD cord-014597-66vd2mdu 662 7 verified verify VBN cord-014597-66vd2mdu 662 8 and and CC cord-014597-66vd2mdu 662 9 evaluated evaluate VBN cord-014597-66vd2mdu 662 10 against against IN cord-014597-66vd2mdu 662 11 other other JJ cord-014597-66vd2mdu 662 12 suppliers supplier NNS cord-014597-66vd2mdu 662 13 ' ' POS cord-014597-66vd2mdu 662 14 galactosylation galactosylation NN cord-014597-66vd2mdu 662 15 supplements supplement NNS cord-014597-66vd2mdu 662 16 in in IN cord-014597-66vd2mdu 662 17 terms term NNS cord-014597-66vd2mdu 662 18 of of IN cord-014597-66vd2mdu 662 19 growth growth NN cord-014597-66vd2mdu 662 20 , , , cord-014597-66vd2mdu 662 21 titer titer NN cord-014597-66vd2mdu 662 22 , , , cord-014597-66vd2mdu 662 23 glycan glycan NN cord-014597-66vd2mdu 662 24 analysis analysis NN cord-014597-66vd2mdu 662 25 , , , cord-014597-66vd2mdu 662 26 and and CC cord-014597-66vd2mdu 662 27 Ab Ab NNP cord-014597-66vd2mdu 662 28 function function NN cord-014597-66vd2mdu 662 29 . . . cord-014597-66vd2mdu 663 1 The the DT cord-014597-66vd2mdu 663 2 Optimized Optimized NNP cord-014597-66vd2mdu 663 3 Supplement Supplement NNP cord-014597-66vd2mdu 663 4 outperformed outperform VBD cord-014597-66vd2mdu 663 5 all all DT cord-014597-66vd2mdu 663 6 other other JJ cord-014597-66vd2mdu 663 7 suppliers supplier NNS cord-014597-66vd2mdu 663 8 ' ' POS cord-014597-66vd2mdu 663 9 supplements supplement NNS cord-014597-66vd2mdu 663 10 and and CC cord-014597-66vd2mdu 663 11 resulted result VBD cord-014597-66vd2mdu 663 12 in in IN cord-014597-66vd2mdu 663 13 the the DT cord-014597-66vd2mdu 663 14 best good JJS cord-014597-66vd2mdu 663 15 overall overall JJ cord-014597-66vd2mdu 663 16 cell cell NN cord-014597-66vd2mdu 663 17 growth growth NN cord-014597-66vd2mdu 663 18 , , , cord-014597-66vd2mdu 663 19 titer titer NN cord-014597-66vd2mdu 663 20 , , , cord-014597-66vd2mdu 663 21 galactosylation galactosylation NN cord-014597-66vd2mdu 663 22 , , , cord-014597-66vd2mdu 663 23 and and CC cord-014597-66vd2mdu 663 24 Ab Ab NNP cord-014597-66vd2mdu 663 25 function function NN cord-014597-66vd2mdu 663 26 . . . cord-014597-66vd2mdu 664 1 Ab Ab NNP cord-014597-66vd2mdu 664 2 against against IN cord-014597-66vd2mdu 664 3 CD20 CD20 NNP cord-014597-66vd2mdu 664 4 were be VBD cord-014597-66vd2mdu 664 5 grown grow VBN cord-014597-66vd2mdu 664 6 in in IN cord-014597-66vd2mdu 664 7 BalanCD BalanCD NNP cord-014597-66vd2mdu 664 8 ® ® POS cord-014597-66vd2mdu 664 9 CHO CHO NNP cord-014597-66vd2mdu 664 10 Growth Growth NNP cord-014597-66vd2mdu 664 11 A A NNP cord-014597-66vd2mdu 664 12 and and CC cord-014597-66vd2mdu 664 13 were be VBD cord-014597-66vd2mdu 664 14 fed feed VBN cord-014597-66vd2mdu 664 15 with with IN cord-014597-66vd2mdu 664 16 BalanCD BalanCD NNP cord-014597-66vd2mdu 664 17 ® ® POS cord-014597-66vd2mdu 664 18 CHO CHO NNP cord-014597-66vd2mdu 664 19 Feed Feed NNP cord-014597-66vd2mdu 664 20 4 4 CD cord-014597-66vd2mdu 664 21 on on IN cord-014597-66vd2mdu 664 22 days day NNS cord-014597-66vd2mdu 664 23 3 3 CD cord-014597-66vd2mdu 664 24 - - SYM cord-014597-66vd2mdu 664 25 7 7 CD cord-014597-66vd2mdu 664 26 of of IN cord-014597-66vd2mdu 664 27 the the DT cord-014597-66vd2mdu 664 28 cultures culture NNS cord-014597-66vd2mdu 664 29 . . . cord-014597-66vd2mdu 665 1 Viable viable JJ cord-014597-66vd2mdu 665 2 cell cell NN cord-014597-66vd2mdu 665 3 density density NN cord-014597-66vd2mdu 665 4 and and CC cord-014597-66vd2mdu 665 5 cell cell NN cord-014597-66vd2mdu 665 6 viability viability NN cord-014597-66vd2mdu 665 7 were be VBD cord-014597-66vd2mdu 665 8 assessed assess VBN cord-014597-66vd2mdu 665 9 by by IN cord-014597-66vd2mdu 665 10 a a DT cord-014597-66vd2mdu 665 11 Beckman Beckman NNP cord-014597-66vd2mdu 665 12 Coulter Coulter NNP cord-014597-66vd2mdu 665 13 Vi Vi NNP cord-014597-66vd2mdu 665 14 - - HYPH cord-014597-66vd2mdu 665 15 Cell Cell NNP cord-014597-66vd2mdu 665 16 XR XR NNP cord-014597-66vd2mdu 665 17 , , , cord-014597-66vd2mdu 665 18 Ab Ab NNP cord-014597-66vd2mdu 665 19 titer titer NN cord-014597-66vd2mdu 665 20 was be VBD cord-014597-66vd2mdu 665 21 assessed assess VBN cord-014597-66vd2mdu 665 22 by by IN cord-014597-66vd2mdu 665 23 a a DT cord-014597-66vd2mdu 665 24 Pall Pall NNP cord-014597-66vd2mdu 665 25 FortéBio FortéBio NNP cord-014597-66vd2mdu 665 26 QK QK NNP cord-014597-66vd2mdu 665 27 e e NN cord-014597-66vd2mdu 665 28 , , , cord-014597-66vd2mdu 665 29 and and CC cord-014597-66vd2mdu 665 30 glycan glycan NN cord-014597-66vd2mdu 665 31 analysis analysis NN cord-014597-66vd2mdu 665 32 was be VBD cord-014597-66vd2mdu 665 33 assessed assess VBN cord-014597-66vd2mdu 665 34 by by IN cord-014597-66vd2mdu 665 35 a a DT cord-014597-66vd2mdu 665 36 PerkinElmer PerkinElmer NNP cord-014597-66vd2mdu 665 37 LabChip LabChip NNP cord-014597-66vd2mdu 665 38 GXII GXII NNP cord-014597-66vd2mdu 665 39 . . . cord-014597-66vd2mdu 666 1 For for IN cord-014597-66vd2mdu 666 2 the the DT cord-014597-66vd2mdu 666 3 functional functional JJ cord-014597-66vd2mdu 666 4 CDC CDC NNP cord-014597-66vd2mdu 666 5 assay assay NN cord-014597-66vd2mdu 666 6 , , , cord-014597-66vd2mdu 666 7 Abs Abs NNP cord-014597-66vd2mdu 666 8 were be VBD cord-014597-66vd2mdu 666 9 incubated incubate VBN cord-014597-66vd2mdu 666 10 with with IN cord-014597-66vd2mdu 666 11 Daudi Daudi NNP cord-014597-66vd2mdu 666 12 B B NNP cord-014597-66vd2mdu 666 13 lymphoblast lymphoblast NN cord-014597-66vd2mdu 666 14 cells cell NNS cord-014597-66vd2mdu 666 15 and and CC cord-014597-66vd2mdu 666 16 normal normal JJ cord-014597-66vd2mdu 666 17 human human JJ cord-014597-66vd2mdu 666 18 complement complement NN cord-014597-66vd2mdu 666 19 serum serum NN cord-014597-66vd2mdu 666 20 . . . cord-014597-66vd2mdu 667 1 Cell cell NN cord-014597-66vd2mdu 667 2 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 667 3 was be VBD cord-014597-66vd2mdu 667 4 assessed assess VBN cord-014597-66vd2mdu 667 5 with with IN cord-014597-66vd2mdu 667 6 a a DT cord-014597-66vd2mdu 667 7 Promega Promega NNP cord-014597-66vd2mdu 667 8 CytoTox CytoTox NNP cord-014597-66vd2mdu 667 9 - - HYPH cord-014597-66vd2mdu 667 10 Glo Glo NNP cord-014597-66vd2mdu 667 11 kit kit NN cord-014597-66vd2mdu 667 12 . . . cord-014597-66vd2mdu 668 1 Various various JJ cord-014597-66vd2mdu 668 2 supplements supplement NNS cord-014597-66vd2mdu 668 3 were be VBD cord-014597-66vd2mdu 668 4 evaluated evaluate VBN cord-014597-66vd2mdu 668 5 in in IN cord-014597-66vd2mdu 668 6 fed fed JJ cord-014597-66vd2mdu 668 7 - - HYPH cord-014597-66vd2mdu 668 8 batch batch NN cord-014597-66vd2mdu 668 9 cultures culture NNS cord-014597-66vd2mdu 668 10 and and CC cord-014597-66vd2mdu 668 11 resulted result VBD cord-014597-66vd2mdu 668 12 in in IN cord-014597-66vd2mdu 668 13 15 15 CD cord-014597-66vd2mdu 668 14 - - SYM cord-014597-66vd2mdu 668 15 45 45 CD cord-014597-66vd2mdu 668 16 % % NN cord-014597-66vd2mdu 668 17 Ab ab NN cord-014597-66vd2mdu 668 18 galactosylation galactosylation NN cord-014597-66vd2mdu 668 19 without without IN cord-014597-66vd2mdu 668 20 compromising compromise VBG cord-014597-66vd2mdu 668 21 cell cell NN cord-014597-66vd2mdu 668 22 growth growth NN cord-014597-66vd2mdu 668 23 and and CC cord-014597-66vd2mdu 668 24 Ab Ab NNP cord-014597-66vd2mdu 668 25 titers titer NNS cord-014597-66vd2mdu 668 26 . . . cord-014597-66vd2mdu 669 1 Design design NN cord-014597-66vd2mdu 669 2 of of IN cord-014597-66vd2mdu 669 3 experiment experiment NN cord-014597-66vd2mdu 669 4 analysis analysis NN cord-014597-66vd2mdu 669 5 determined determine VBD cord-014597-66vd2mdu 669 6 an an DT cord-014597-66vd2mdu 669 7 optimal optimal JJ cord-014597-66vd2mdu 669 8 composition composition NN cord-014597-66vd2mdu 669 9 , , , cord-014597-66vd2mdu 669 10 deemed deem VBN cord-014597-66vd2mdu 669 11 " " `` cord-014597-66vd2mdu 669 12 Optimized optimize VBN cord-014597-66vd2mdu 669 13 Supplement Supplement NNP cord-014597-66vd2mdu 669 14 , , , cord-014597-66vd2mdu 669 15 " " '' cord-014597-66vd2mdu 669 16 which which WDT cord-014597-66vd2mdu 669 17 was be VBD cord-014597-66vd2mdu 669 18 evaluated evaluate VBN cord-014597-66vd2mdu 669 19 against against IN cord-014597-66vd2mdu 669 20 a a DT cord-014597-66vd2mdu 669 21 panel panel NN cord-014597-66vd2mdu 669 22 of of IN cord-014597-66vd2mdu 669 23 galactose galactose NN cord-014597-66vd2mdu 669 24 - - HYPH cord-014597-66vd2mdu 669 25 modulating modulate VBG cord-014597-66vd2mdu 669 26 supplements supplement NNS cord-014597-66vd2mdu 669 27 from from IN cord-014597-66vd2mdu 669 28 other other JJ cord-014597-66vd2mdu 669 29 suppliers supplier NNS cord-014597-66vd2mdu 669 30 . . . cord-014597-66vd2mdu 670 1 The the DT cord-014597-66vd2mdu 670 2 Optimized Optimized NNP cord-014597-66vd2mdu 670 3 Supplement Supplement NNP cord-014597-66vd2mdu 670 4 resulted result VBD cord-014597-66vd2mdu 670 5 in in IN cord-014597-66vd2mdu 670 6 a a DT cord-014597-66vd2mdu 670 7 similar similar JJ cord-014597-66vd2mdu 670 8 viable viable JJ cord-014597-66vd2mdu 670 9 cell cell NN cord-014597-66vd2mdu 670 10 density density NN cord-014597-66vd2mdu 670 11 ( ( -LRB- cord-014597-66vd2mdu 670 12 VCD VCD NNP cord-014597-66vd2mdu 670 13 ) ) -RRB- cord-014597-66vd2mdu 670 14 and and CC cord-014597-66vd2mdu 670 15 cell cell NN cord-014597-66vd2mdu 670 16 viability viability NN cord-014597-66vd2mdu 670 17 compared compare VBN cord-014597-66vd2mdu 670 18 to to IN cord-014597-66vd2mdu 670 19 the the DT cord-014597-66vd2mdu 670 20 fed feed VBN cord-014597-66vd2mdu 670 21 - - HYPH cord-014597-66vd2mdu 670 22 batch batch NN cord-014597-66vd2mdu 670 23 culture culture NN cord-014597-66vd2mdu 670 24 Control Control NNP cord-014597-66vd2mdu 670 25 which which WDT cord-014597-66vd2mdu 670 26 had have VBD cord-014597-66vd2mdu 670 27 no no DT cord-014597-66vd2mdu 670 28 supplements supplement NNS cord-014597-66vd2mdu 670 29 ( ( -LRB- cord-014597-66vd2mdu 670 30 Fig fig NN cord-014597-66vd2mdu 670 31 . . . cord-014597-66vd2mdu 670 32 1a 1a CD cord-014597-66vd2mdu 670 33 ) ) -RRB- cord-014597-66vd2mdu 670 34 . . . cord-014597-66vd2mdu 671 1 Supplements supplement NNS cord-014597-66vd2mdu 671 2 from from IN cord-014597-66vd2mdu 671 3 Supplier Supplier NNP cord-014597-66vd2mdu 671 4 1 1 CD cord-014597-66vd2mdu 671 5 resulted result VBD cord-014597-66vd2mdu 671 6 in in IN cord-014597-66vd2mdu 671 7 similar similar JJ cord-014597-66vd2mdu 671 8 to to IN cord-014597-66vd2mdu 671 9 half half PDT cord-014597-66vd2mdu 671 10 the the DT cord-014597-66vd2mdu 671 11 VCD vcd NN cord-014597-66vd2mdu 671 12 of of IN cord-014597-66vd2mdu 671 13 the the DT cord-014597-66vd2mdu 671 14 Control Control NNP cord-014597-66vd2mdu 671 15 while while IN cord-014597-66vd2mdu 671 16 supplements supplement NNS cord-014597-66vd2mdu 671 17 from from IN cord-014597-66vd2mdu 671 18 Supplier Supplier NNP cord-014597-66vd2mdu 671 19 2 2 CD cord-014597-66vd2mdu 671 20 resulted result VBD cord-014597-66vd2mdu 671 21 in in IN cord-014597-66vd2mdu 671 22 very very RB cord-014597-66vd2mdu 671 23 low low JJ cord-014597-66vd2mdu 671 24 VCD vcd NN cord-014597-66vd2mdu 671 25 and and CC cord-014597-66vd2mdu 671 26 percent percent NN cord-014597-66vd2mdu 671 27 viability viability NN cord-014597-66vd2mdu 671 28 . . . cord-014597-66vd2mdu 672 1 All all DT cord-014597-66vd2mdu 672 2 of of IN cord-014597-66vd2mdu 672 3 the the DT cord-014597-66vd2mdu 672 4 supplements supplement NNS cord-014597-66vd2mdu 672 5 except except IN cord-014597-66vd2mdu 672 6 those those DT cord-014597-66vd2mdu 672 7 from from IN cord-014597-66vd2mdu 672 8 Supplier Supplier NNP cord-014597-66vd2mdu 672 9 2 2 CD cord-014597-66vd2mdu 672 10 resulted result VBD cord-014597-66vd2mdu 672 11 in in IN cord-014597-66vd2mdu 672 12 Ab Ab NNP cord-014597-66vd2mdu 672 13 titers titer NNS cord-014597-66vd2mdu 672 14 similar similar JJ cord-014597-66vd2mdu 672 15 to to IN cord-014597-66vd2mdu 672 16 the the DT cord-014597-66vd2mdu 672 17 Control Control NNP cord-014597-66vd2mdu 673 1 ( ( -LRB- cord-014597-66vd2mdu 673 2 Fig Fig NNP cord-014597-66vd2mdu 673 3 . . . cord-014597-66vd2mdu 673 4 1b 1b CD cord-014597-66vd2mdu 673 5 ) ) -RRB- cord-014597-66vd2mdu 673 6 . . . cord-014597-66vd2mdu 674 1 Due due IN cord-014597-66vd2mdu 674 2 to to IN cord-014597-66vd2mdu 674 3 the the DT cord-014597-66vd2mdu 674 4 poor poor JJ cord-014597-66vd2mdu 674 5 growth growth NN cord-014597-66vd2mdu 674 6 and and CC cord-014597-66vd2mdu 674 7 subsequently subsequently RB cord-014597-66vd2mdu 674 8 low low JJ cord-014597-66vd2mdu 674 9 titer titer NN cord-014597-66vd2mdu 674 10 from from IN cord-014597-66vd2mdu 674 11 Supplier Supplier NNP cord-014597-66vd2mdu 674 12 2 2 CD cord-014597-66vd2mdu 674 13 's 's POS cord-014597-66vd2mdu 674 14 supplement supplement NN cord-014597-66vd2mdu 674 15 , , , cord-014597-66vd2mdu 674 16 Supplier Supplier NNP cord-014597-66vd2mdu 674 17 2 2 CD cord-014597-66vd2mdu 674 18 was be VBD cord-014597-66vd2mdu 674 19 not not RB cord-014597-66vd2mdu 674 20 further further RB cord-014597-66vd2mdu 674 21 evaluated evaluate VBN cord-014597-66vd2mdu 674 22 . . . cord-014597-66vd2mdu 675 1 The the DT cord-014597-66vd2mdu 675 2 glycan glycan NN cord-014597-66vd2mdu 675 3 profiles profile NNS cord-014597-66vd2mdu 675 4 were be VBD cord-014597-66vd2mdu 675 5 analyzed analyze VBN cord-014597-66vd2mdu 675 6 and and CC cord-014597-66vd2mdu 675 7 are be VBP cord-014597-66vd2mdu 675 8 presented present VBN cord-014597-66vd2mdu 675 9 in in IN cord-014597-66vd2mdu 675 10 ( ( -LRB- cord-014597-66vd2mdu 675 11 Fig Fig NNP cord-014597-66vd2mdu 675 12 . . . cord-014597-66vd2mdu 675 13 1c 1c CD cord-014597-66vd2mdu 675 14 ) ) -RRB- cord-014597-66vd2mdu 675 15 . . . cord-014597-66vd2mdu 676 1 All all PDT cord-014597-66vd2mdu 676 2 the the DT cord-014597-66vd2mdu 676 3 evaluated evaluate VBN cord-014597-66vd2mdu 676 4 supplements supplement NNS cord-014597-66vd2mdu 676 5 were be VBD cord-014597-66vd2mdu 676 6 able able JJ cord-014597-66vd2mdu 676 7 to to TO cord-014597-66vd2mdu 676 8 raise raise VB cord-014597-66vd2mdu 676 9 galactosylation galactosylation NN cord-014597-66vd2mdu 676 10 ; ; : cord-014597-66vd2mdu 676 11 however however RB cord-014597-66vd2mdu 676 12 , , , cord-014597-66vd2mdu 676 13 only only RB cord-014597-66vd2mdu 676 14 the the DT cord-014597-66vd2mdu 676 15 Optimized Optimized NNP cord-014597-66vd2mdu 676 16 Supplement Supplement NNP cord-014597-66vd2mdu 676 17 and and CC cord-014597-66vd2mdu 676 18 the the DT cord-014597-66vd2mdu 676 19 2X 2x CD cord-014597-66vd2mdu 676 20 Supplier Supplier NNP cord-014597-66vd2mdu 676 21 1 1 CD cord-014597-66vd2mdu 676 22 Supplement Supplement NNP cord-014597-66vd2mdu 676 23 resulted result VBD cord-014597-66vd2mdu 676 24 in in IN cord-014597-66vd2mdu 676 25 over over IN cord-014597-66vd2mdu 676 26 40 40 CD cord-014597-66vd2mdu 676 27 % % NN cord-014597-66vd2mdu 676 28 galactosylation galactosylation NN cord-014597-66vd2mdu 676 29 . . . cord-014597-66vd2mdu 677 1 The the DT cord-014597-66vd2mdu 677 2 function function NN cord-014597-66vd2mdu 677 3 of of IN cord-014597-66vd2mdu 677 4 the the DT cord-014597-66vd2mdu 677 5 Abs Abs NNP cord-014597-66vd2mdu 677 6 was be VBD cord-014597-66vd2mdu 677 7 further further RB cord-014597-66vd2mdu 677 8 evaluated evaluate VBN cord-014597-66vd2mdu 677 9 in in IN cord-014597-66vd2mdu 677 10 a a DT cord-014597-66vd2mdu 677 11 CDC CDC NNP cord-014597-66vd2mdu 677 12 assay assay NN cord-014597-66vd2mdu 677 13 ( ( -LRB- cord-014597-66vd2mdu 677 14 Fig Fig NNP cord-014597-66vd2mdu 677 15 . . . cord-014597-66vd2mdu 677 16 1d 1d CD cord-014597-66vd2mdu 677 17 ) ) -RRB- cord-014597-66vd2mdu 677 18 . . . cord-014597-66vd2mdu 678 1 Abs abs NN cord-014597-66vd2mdu 678 2 from from IN cord-014597-66vd2mdu 678 3 the the DT cord-014597-66vd2mdu 678 4 Optimized Optimized NNP cord-014597-66vd2mdu 678 5 Supplement Supplement NNP cord-014597-66vd2mdu 678 6 were be VBD cord-014597-66vd2mdu 678 7 more more RBR cord-014597-66vd2mdu 678 8 effective effective JJ cord-014597-66vd2mdu 678 9 than than IN cord-014597-66vd2mdu 678 10 the the DT cord-014597-66vd2mdu 678 11 Control Control NNP cord-014597-66vd2mdu 678 12 Abs Abs NNP cord-014597-66vd2mdu 678 13 and and CC cord-014597-66vd2mdu 678 14 had have VBD cord-014597-66vd2mdu 678 15 a a DT cord-014597-66vd2mdu 678 16 significantly significantly RB cord-014597-66vd2mdu 678 17 lower low JJR cord-014597-66vd2mdu 678 18 half half RB cord-014597-66vd2mdu 678 19 - - HYPH cord-014597-66vd2mdu 678 20 maximal maximal JJ cord-014597-66vd2mdu 678 21 effective effective JJ cord-014597-66vd2mdu 678 22 concentration concentration NN cord-014597-66vd2mdu 678 23 ( ( -LRB- cord-014597-66vd2mdu 678 24 EC EC NNP cord-014597-66vd2mdu 678 25 50 50 CD cord-014597-66vd2mdu 678 26 , , , cord-014597-66vd2mdu 678 27 1.19 1.19 CD cord-014597-66vd2mdu 678 28 μg μg NN cord-014597-66vd2mdu 678 29 / / SYM cord-014597-66vd2mdu 678 30 mL mL NNP cord-014597-66vd2mdu 678 31 ) ) -RRB- cord-014597-66vd2mdu 678 32 than than IN cord-014597-66vd2mdu 678 33 the the DT cord-014597-66vd2mdu 678 34 Control Control NNP cord-014597-66vd2mdu 678 35 ( ( -LRB- cord-014597-66vd2mdu 678 36 1.71 1.71 CD cord-014597-66vd2mdu 678 37 μg μg NNP cord-014597-66vd2mdu 678 38 / / SYM cord-014597-66vd2mdu 678 39 mL mL NNP cord-014597-66vd2mdu 678 40 ) ) -RRB- cord-014597-66vd2mdu 678 41 . . . cord-014597-66vd2mdu 679 1 Abs abs NN cord-014597-66vd2mdu 679 2 from from IN cord-014597-66vd2mdu 679 3 the the DT cord-014597-66vd2mdu 679 4 2X 2x CD cord-014597-66vd2mdu 679 5 Supplier Supplier NNP cord-014597-66vd2mdu 679 6 1 1 CD cord-014597-66vd2mdu 679 7 Supplement Supplement NNP cord-014597-66vd2mdu 679 8 had have VBD cord-014597-66vd2mdu 679 9 a a DT cord-014597-66vd2mdu 679 10 similar similar JJ cord-014597-66vd2mdu 679 11 EC EC NNP cord-014597-66vd2mdu 679 12 50 50 CD cord-014597-66vd2mdu 679 13 to to IN cord-014597-66vd2mdu 679 14 the the DT cord-014597-66vd2mdu 679 15 Control Control NNP cord-014597-66vd2mdu 679 16 which which WDT cord-014597-66vd2mdu 679 17 may may MD cord-014597-66vd2mdu 679 18 be be VB cord-014597-66vd2mdu 679 19 due due JJ cord-014597-66vd2mdu 679 20 to to IN cord-014597-66vd2mdu 679 21 the the DT cord-014597-66vd2mdu 679 22 higher high JJR cord-014597-66vd2mdu 679 23 Man5 Man5 NNP cord-014597-66vd2mdu 679 24 % % NN cord-014597-66vd2mdu 679 25 of of IN cord-014597-66vd2mdu 679 26 the the DT cord-014597-66vd2mdu 679 27 Abs Abs NNP cord-014597-66vd2mdu 679 28 . . . cord-014597-66vd2mdu 680 1 An an DT cord-014597-66vd2mdu 680 2 Optimized optimize VBN cord-014597-66vd2mdu 680 3 Supplement Supplement NNP cord-014597-66vd2mdu 680 4 was be VBD cord-014597-66vd2mdu 680 5 produced produce VBN cord-014597-66vd2mdu 680 6 through through IN cord-014597-66vd2mdu 680 7 fed fed JJ cord-014597-66vd2mdu 680 8 - - HYPH cord-014597-66vd2mdu 680 9 batch batch NN cord-014597-66vd2mdu 680 10 evaluation evaluation NN cord-014597-66vd2mdu 680 11 and and CC cord-014597-66vd2mdu 680 12 design design NN cord-014597-66vd2mdu 680 13 of of IN cord-014597-66vd2mdu 680 14 experiment experiment NN cord-014597-66vd2mdu 680 15 analysis analysis NN cord-014597-66vd2mdu 680 16 . . . cord-014597-66vd2mdu 681 1 The the DT cord-014597-66vd2mdu 681 2 Optimized Optimized NNP cord-014597-66vd2mdu 681 3 Supplement Supplement NNP cord-014597-66vd2mdu 681 4 outperformed outperform VBD cord-014597-66vd2mdu 681 5 all all DT cord-014597-66vd2mdu 681 6 other other JJ cord-014597-66vd2mdu 681 7 supplenments supplenment NNS cord-014597-66vd2mdu 681 8 from from IN cord-014597-66vd2mdu 681 9 other other JJ cord-014597-66vd2mdu 681 10 suppliers supplier NNS cord-014597-66vd2mdu 681 11 and and CC cord-014597-66vd2mdu 681 12 resulted result VBD cord-014597-66vd2mdu 681 13 in in IN cord-014597-66vd2mdu 681 14 the the DT cord-014597-66vd2mdu 681 15 best good JJS cord-014597-66vd2mdu 681 16 overall overall JJ cord-014597-66vd2mdu 681 17 cell cell NN cord-014597-66vd2mdu 681 18 growth growth NN cord-014597-66vd2mdu 681 19 , , , cord-014597-66vd2mdu 681 20 glycan glycan NN cord-014597-66vd2mdu 681 21 profile profile NN cord-014597-66vd2mdu 681 22 , , , cord-014597-66vd2mdu 681 23 and and CC cord-014597-66vd2mdu 681 24 functional functional JJ cord-014597-66vd2mdu 681 25 Ab ab NN cord-014597-66vd2mdu 681 26 activity activity NN cord-014597-66vd2mdu 681 27 ( ( -LRB- cord-014597-66vd2mdu 681 28 Table table NN cord-014597-66vd2mdu 681 29 1 1 CD cord-014597-66vd2mdu 681 30 ) ) -RRB- cord-014597-66vd2mdu 681 31 . . . cord-014597-66vd2mdu 682 1 Industry industry NN cord-014597-66vd2mdu 682 2 practice practice NN cord-014597-66vd2mdu 682 3 for for IN cord-014597-66vd2mdu 682 4 mammalian mammalian JJ cord-014597-66vd2mdu 682 5 cell cell NN cord-014597-66vd2mdu 682 6 culture culture NN cord-014597-66vd2mdu 682 7 media medium NNS cord-014597-66vd2mdu 682 8 and and CC cord-014597-66vd2mdu 682 9 feed feed NN cord-014597-66vd2mdu 682 10 development development NN cord-014597-66vd2mdu 682 11 typically typically RB cord-014597-66vd2mdu 682 12 employs employ VBZ cord-014597-66vd2mdu 682 13 a a DT cord-014597-66vd2mdu 682 14 high high JJ cord-014597-66vd2mdu 682 15 - - HYPH cord-014597-66vd2mdu 682 16 throughput throughput NN cord-014597-66vd2mdu 682 17 screening screening NN cord-014597-66vd2mdu 682 18 ( ( -LRB- cord-014597-66vd2mdu 682 19 HTS HTS NNP cord-014597-66vd2mdu 682 20 ) ) -RRB- cord-014597-66vd2mdu 682 21 platform platform NN cord-014597-66vd2mdu 682 22 along along IN cord-014597-66vd2mdu 682 23 with with IN cord-014597-66vd2mdu 682 24 large large JJ cord-014597-66vd2mdu 682 25 sets set NNS cord-014597-66vd2mdu 682 26 of of IN cord-014597-66vd2mdu 682 27 experiments experiment NNS cord-014597-66vd2mdu 682 28 [ [ -LRB- cord-014597-66vd2mdu 682 29 1 1 CD cord-014597-66vd2mdu 682 30 ] ] -RRB- cord-014597-66vd2mdu 682 31 . . . cord-014597-66vd2mdu 683 1 Modern modern JJ cord-014597-66vd2mdu 683 2 HTS HTS NNP cord-014597-66vd2mdu 683 3 systems system NNS cord-014597-66vd2mdu 683 4 often often RB cord-014597-66vd2mdu 683 5 include include VBP cord-014597-66vd2mdu 683 6 robotic robotic JJ cord-014597-66vd2mdu 683 7 liquid liquid JJ cord-014597-66vd2mdu 683 8 handlers handler NNS cord-014597-66vd2mdu 683 9 to to TO cord-014597-66vd2mdu 683 10 replace replace VB cord-014597-66vd2mdu 683 11 labor labor NN cord-014597-66vd2mdu 683 12 intensive intensive JJ cord-014597-66vd2mdu 683 13 steps step NNS cord-014597-66vd2mdu 683 14 . . . cord-014597-66vd2mdu 684 1 To to TO cord-014597-66vd2mdu 684 2 align align VB cord-014597-66vd2mdu 684 3 with with IN cord-014597-66vd2mdu 684 4 advancements advancement NNS cord-014597-66vd2mdu 684 5 in in IN cord-014597-66vd2mdu 684 6 the the DT cord-014597-66vd2mdu 684 7 field field NN cord-014597-66vd2mdu 684 8 , , , cord-014597-66vd2mdu 684 9 a a DT cord-014597-66vd2mdu 684 10 semi semi RB cord-014597-66vd2mdu 684 11 - - JJ cord-014597-66vd2mdu 684 12 automated automated JJ cord-014597-66vd2mdu 684 13 HTS HTS NNP cord-014597-66vd2mdu 684 14 platform platform NN cord-014597-66vd2mdu 684 15 was be VBD cord-014597-66vd2mdu 684 16 developed develop VBN cord-014597-66vd2mdu 684 17 to to TO cord-014597-66vd2mdu 684 18 facilitate facilitate VB cord-014597-66vd2mdu 684 19 in in IN cord-014597-66vd2mdu 684 20 - - HYPH cord-014597-66vd2mdu 684 21 house house NN cord-014597-66vd2mdu 684 22 media medium NNS cord-014597-66vd2mdu 684 23 and and CC cord-014597-66vd2mdu 684 24 feed feed VB cord-014597-66vd2mdu 684 25 development development NN cord-014597-66vd2mdu 684 26 for for IN cord-014597-66vd2mdu 684 27 early early JJ cord-014597-66vd2mdu 684 28 stage stage NN cord-014597-66vd2mdu 684 29 biologics biologic NNS cord-014597-66vd2mdu 684 30 projects project NNS cord-014597-66vd2mdu 684 31 . . . cord-014597-66vd2mdu 685 1 Selecting select VBG cord-014597-66vd2mdu 685 2 appropriate appropriate JJ cord-014597-66vd2mdu 685 3 instruments instrument NNS cord-014597-66vd2mdu 685 4 and and CC cord-014597-66vd2mdu 685 5 integrating integrate VBG cord-014597-66vd2mdu 685 6 them -PRON- PRP cord-014597-66vd2mdu 685 7 into into IN cord-014597-66vd2mdu 685 8 a a DT cord-014597-66vd2mdu 685 9 seamless seamless JJ cord-014597-66vd2mdu 685 10 system system NN cord-014597-66vd2mdu 685 11 are be VBP cord-014597-66vd2mdu 685 12 the the DT cord-014597-66vd2mdu 685 13 keys key NNS cord-014597-66vd2mdu 685 14 to to IN cord-014597-66vd2mdu 685 15 a a DT cord-014597-66vd2mdu 685 16 HTS HTS NNP cord-014597-66vd2mdu 685 17 platform platform NN cord-014597-66vd2mdu 685 18 . . . cord-014597-66vd2mdu 686 1 The the DT cord-014597-66vd2mdu 686 2 developed developed JJ cord-014597-66vd2mdu 686 3 HTS HTS NNP cord-014597-66vd2mdu 686 4 platform platform NN cord-014597-66vd2mdu 686 5 uses use VBZ cord-014597-66vd2mdu 686 6 24 24 CD cord-014597-66vd2mdu 686 7 deep deep JJ cord-014597-66vd2mdu 686 8 well well NN cord-014597-66vd2mdu 686 9 plates plate NNS cord-014597-66vd2mdu 686 10 ( ( -LRB- cord-014597-66vd2mdu 686 11 DWPs DWPs NNP cord-014597-66vd2mdu 686 12 ) ) -RRB- cord-014597-66vd2mdu 686 13 for for IN cord-014597-66vd2mdu 686 14 culture culture NN cord-014597-66vd2mdu 686 15 vessels vessel NNS cord-014597-66vd2mdu 686 16 , , , cord-014597-66vd2mdu 686 17 the the DT cord-014597-66vd2mdu 686 18 liquid liquid JJ cord-014597-66vd2mdu 686 19 handler handler NN cord-014597-66vd2mdu 686 20 of of IN cord-014597-66vd2mdu 686 21 the the DT cord-014597-66vd2mdu 686 22 Advance Advance NNP cord-014597-66vd2mdu 686 23 Microscale Microscale NNP cord-014597-66vd2mdu 686 24 BioReactor BioReactor NNP cord-014597-66vd2mdu 686 25 ( ( -LRB- cord-014597-66vd2mdu 686 26 AMBR15 ambr15 NN cord-014597-66vd2mdu 686 27 ) ) -RRB- cord-014597-66vd2mdu 686 28 for for IN cord-014597-66vd2mdu 686 29 media/ media/ ADD cord-014597-66vd2mdu 686 30 feed feed NN cord-014597-66vd2mdu 686 31 formulation formulation NN cord-014597-66vd2mdu 686 32 preparation preparation NN cord-014597-66vd2mdu 686 33 in in IN cord-014597-66vd2mdu 686 34 an an DT cord-014597-66vd2mdu 686 35 aseptic aseptic JJ cord-014597-66vd2mdu 686 36 environment environment NN cord-014597-66vd2mdu 686 37 , , , cord-014597-66vd2mdu 686 38 NyONE NyONE NNP cord-014597-66vd2mdu 686 39 cell cell NN cord-014597-66vd2mdu 686 40 imager imager NN cord-014597-66vd2mdu 686 41 for for IN cord-014597-66vd2mdu 686 42 viability viability NN cord-014597-66vd2mdu 686 43 and and CC cord-014597-66vd2mdu 686 44 cell cell NN cord-014597-66vd2mdu 686 45 growth growth NN cord-014597-66vd2mdu 686 46 analysis analysis NN cord-014597-66vd2mdu 686 47 , , , cord-014597-66vd2mdu 686 48 TECAN TECAN NNP cord-014597-66vd2mdu 686 49 Freedom Freedom NNP cord-014597-66vd2mdu 686 50 EVO EVO NNP cord-014597-66vd2mdu 686 51 's 's POS cord-014597-66vd2mdu 686 52 liquid liquid JJ cord-014597-66vd2mdu 686 53 handler handler NN cord-014597-66vd2mdu 686 54 for for IN cord-014597-66vd2mdu 686 55 activity activity NN cord-014597-66vd2mdu 686 56 assay assay NN cord-014597-66vd2mdu 686 57 sample sample NN cord-014597-66vd2mdu 686 58 preparation preparation NN cord-014597-66vd2mdu 686 59 , , , cord-014597-66vd2mdu 686 60 and and CC cord-014597-66vd2mdu 686 61 Cedex Cedex NNP cord-014597-66vd2mdu 686 62 BioHT BioHT NNP cord-014597-66vd2mdu 686 63 for for IN cord-014597-66vd2mdu 686 64 high high JJ cord-014597-66vd2mdu 686 65 - - HYPH cord-014597-66vd2mdu 686 66 throughput throughput NN cord-014597-66vd2mdu 686 67 metabolite metabolite NN cord-014597-66vd2mdu 686 68 analysis analysis NN cord-014597-66vd2mdu 686 69 . . . cord-014597-66vd2mdu 687 1 24 24 CD cord-014597-66vd2mdu 687 2 DWPs dwp NNS cord-014597-66vd2mdu 687 3 offer offer VBP cord-014597-66vd2mdu 687 4 comparable comparable JJ cord-014597-66vd2mdu 687 5 cell cell NN cord-014597-66vd2mdu 687 6 growth growth NN cord-014597-66vd2mdu 687 7 to to TO cord-014597-66vd2mdu 687 8 shake shake VB cord-014597-66vd2mdu 687 9 flasks flask NNS cord-014597-66vd2mdu 687 10 and and CC cord-014597-66vd2mdu 687 11 compatible compatible JJ cord-014597-66vd2mdu 687 12 layout layout NN cord-014597-66vd2mdu 687 13 to to IN cord-014597-66vd2mdu 687 14 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 687 15 , , , cord-014597-66vd2mdu 687 16 which which WDT cord-014597-66vd2mdu 687 17 makes make VBZ cord-014597-66vd2mdu 687 18 the the DT cord-014597-66vd2mdu 687 19 24 24 CD cord-014597-66vd2mdu 687 20 DWP DWP NNP cord-014597-66vd2mdu 687 21 an an DT cord-014597-66vd2mdu 687 22 ideal ideal JJ cord-014597-66vd2mdu 687 23 candidate candidate NN cord-014597-66vd2mdu 687 24 for for IN cord-014597-66vd2mdu 687 25 the the DT cord-014597-66vd2mdu 687 26 platform platform NN cord-014597-66vd2mdu 687 27 . . . cord-014597-66vd2mdu 688 1 In in IN cord-014597-66vd2mdu 688 2 addition addition NN cord-014597-66vd2mdu 688 3 , , , cord-014597-66vd2mdu 688 4 the the DT cord-014597-66vd2mdu 688 5 user user NN cord-014597-66vd2mdu 688 6 friendly friendly JJ cord-014597-66vd2mdu 688 7 Design design NN cord-014597-66vd2mdu 688 8 of of IN cord-014597-66vd2mdu 688 9 Experiments Experiments NNP cord-014597-66vd2mdu 688 10 ( ( -LRB- cord-014597-66vd2mdu 688 11 DoEs does JJ cord-014597-66vd2mdu 688 12 ) ) -RRB- cord-014597-66vd2mdu 688 13 interface interface NN cord-014597-66vd2mdu 688 14 and and CC cord-014597-66vd2mdu 688 15 liquid liquid JJ cord-014597-66vd2mdu 688 16 handler handler NN cord-014597-66vd2mdu 688 17 function function NN cord-014597-66vd2mdu 688 18 of of IN cord-014597-66vd2mdu 688 19 the the DT cord-014597-66vd2mdu 688 20 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 688 21 expediates expediate VBZ cord-014597-66vd2mdu 688 22 the the DT cord-014597-66vd2mdu 688 23 formulation formulation NN cord-014597-66vd2mdu 688 24 preparation preparation NN cord-014597-66vd2mdu 688 25 of of IN cord-014597-66vd2mdu 688 26 varying vary VBG cord-014597-66vd2mdu 688 27 DoE doe NN cord-014597-66vd2mdu 688 28 conditions condition NNS cord-014597-66vd2mdu 688 29 [ [ -LRB- cord-014597-66vd2mdu 688 30 2 2 CD cord-014597-66vd2mdu 688 31 ] ] -RRB- cord-014597-66vd2mdu 688 32 . . . cord-014597-66vd2mdu 689 1 A a DT cord-014597-66vd2mdu 689 2 macro macro JJ cord-014597-66vd2mdu 689 3 program program NN cord-014597-66vd2mdu 689 4 was be VBD cord-014597-66vd2mdu 689 5 written write VBN cord-014597-66vd2mdu 689 6 and and CC cord-014597-66vd2mdu 689 7 developed develop VBN cord-014597-66vd2mdu 689 8 in in IN cord-014597-66vd2mdu 689 9 Excel Excel NNP cord-014597-66vd2mdu 689 10 to to TO cord-014597-66vd2mdu 689 11 enable enable VB cord-014597-66vd2mdu 689 12 the the DT cord-014597-66vd2mdu 689 13 easy easy JJ cord-014597-66vd2mdu 689 14 import import NN cord-014597-66vd2mdu 689 15 of of IN cord-014597-66vd2mdu 689 16 DoEs DoEs NNP cord-014597-66vd2mdu 689 17 design design NN cord-014597-66vd2mdu 689 18 from from IN cord-014597-66vd2mdu 689 19 major major JJ cord-014597-66vd2mdu 689 20 statistics statistic NNS cord-014597-66vd2mdu 689 21 software software NN cord-014597-66vd2mdu 689 22 packages package NNS cord-014597-66vd2mdu 689 23 , , , cord-014597-66vd2mdu 689 24 such such JJ cord-014597-66vd2mdu 689 25 as as IN cord-014597-66vd2mdu 689 26 JMP JMP NNP cord-014597-66vd2mdu 689 27 and and CC cord-014597-66vd2mdu 689 28 Simca Simca NNP cord-014597-66vd2mdu 689 29 , , , cord-014597-66vd2mdu 689 30 into into IN cord-014597-66vd2mdu 689 31 AMBR15 ambr15 NN cord-014597-66vd2mdu 689 32 . . . cord-014597-66vd2mdu 690 1 Performance performance NN cord-014597-66vd2mdu 690 2 qualification qualification NN cord-014597-66vd2mdu 690 3 of of IN cord-014597-66vd2mdu 690 4 each each DT cord-014597-66vd2mdu 690 5 component component NN cord-014597-66vd2mdu 690 6 were be VBD cord-014597-66vd2mdu 690 7 performed perform VBN cord-014597-66vd2mdu 690 8 prior prior RB cord-014597-66vd2mdu 690 9 to to IN cord-014597-66vd2mdu 690 10 implementing implement VBG cord-014597-66vd2mdu 690 11 the the DT cord-014597-66vd2mdu 690 12 HTS HTS NNP cord-014597-66vd2mdu 690 13 platform platform NN cord-014597-66vd2mdu 690 14 . . . cord-014597-66vd2mdu 691 1 Comparable comparable JJ cord-014597-66vd2mdu 691 2 cell cell NN cord-014597-66vd2mdu 691 3 growth growth NN cord-014597-66vd2mdu 691 4 profile profile NN cord-014597-66vd2mdu 691 5 and and CC cord-014597-66vd2mdu 691 6 productivity productivity NN cord-014597-66vd2mdu 691 7 were be VBD cord-014597-66vd2mdu 691 8 achived achive VBN cord-014597-66vd2mdu 691 9 between between IN cord-014597-66vd2mdu 691 10 shake shake NN cord-014597-66vd2mdu 691 11 flasks flask NNS cord-014597-66vd2mdu 691 12 and and CC cord-014597-66vd2mdu 691 13 24 24 CD cord-014597-66vd2mdu 691 14 DWPs dwp NNS cord-014597-66vd2mdu 691 15 ( ( -LRB- cord-014597-66vd2mdu 691 16 Fig Fig NNP cord-014597-66vd2mdu 691 17 . . . cord-014597-66vd2mdu 691 18 1a 1a CD cord-014597-66vd2mdu 691 19 ) ) -RRB- cord-014597-66vd2mdu 691 20 , , , cord-014597-66vd2mdu 691 21 indicating indicate VBG cord-014597-66vd2mdu 691 22 compatable compatable JJ cord-014597-66vd2mdu 691 23 cell cell NN cord-014597-66vd2mdu 691 24 culture culture NN cord-014597-66vd2mdu 691 25 environment environment NN cord-014597-66vd2mdu 691 26 for for IN cord-014597-66vd2mdu 691 27 the the DT cord-014597-66vd2mdu 691 28 cells cell NNS cord-014597-66vd2mdu 691 29 . . . cord-014597-66vd2mdu 692 1 Cell cell NN cord-014597-66vd2mdu 692 2 counts count VBZ cord-014597-66vd2mdu 692 3 using use VBG cord-014597-66vd2mdu 692 4 NyONE NyONE NNP cord-014597-66vd2mdu 692 5 gave give VBD cord-014597-66vd2mdu 692 6 identical identical JJ cord-014597-66vd2mdu 692 7 cell cell NN cord-014597-66vd2mdu 692 8 growth growth NN cord-014597-66vd2mdu 692 9 ranking rank VBG cord-014597-66vd2mdu 692 10 as as IN cord-014597-66vd2mdu 692 11 the the DT cord-014597-66vd2mdu 692 12 traditional traditional JJ cord-014597-66vd2mdu 692 13 count count NN cord-014597-66vd2mdu 692 14 from from IN cord-014597-66vd2mdu 692 15 Vi Vi NNP cord-014597-66vd2mdu 692 16 - - HYPH cord-014597-66vd2mdu 692 17 Cell Cell NNP cord-014597-66vd2mdu 692 18 XR XR NNP cord-014597-66vd2mdu 692 19 ( ( -LRB- cord-014597-66vd2mdu 692 20 Fig fig NN cord-014597-66vd2mdu 692 21 . . . cord-014597-66vd2mdu 692 22 1b 1b CD cord-014597-66vd2mdu 692 23 ) ) -RRB- cord-014597-66vd2mdu 692 24 . . . cord-014597-66vd2mdu 693 1 Freedom Freedom NNP cord-014597-66vd2mdu 693 2 EVO EVO NNP cord-014597-66vd2mdu 693 3 's 's POS cord-014597-66vd2mdu 693 4 liquid liquid JJ cord-014597-66vd2mdu 693 5 handler handler NN cord-014597-66vd2mdu 693 6 was be VBD cord-014597-66vd2mdu 693 7 optimized optimize VBN cord-014597-66vd2mdu 693 8 to to TO cord-014597-66vd2mdu 693 9 produce produce VB cord-014597-66vd2mdu 693 10 comparable comparable JJ cord-014597-66vd2mdu 693 11 activity activity NN cord-014597-66vd2mdu 693 12 results result NNS cord-014597-66vd2mdu 693 13 to to IN cord-014597-66vd2mdu 693 14 manual manual JJ cord-014597-66vd2mdu 693 15 operation operation NN cord-014597-66vd2mdu 693 16 while while IN cord-014597-66vd2mdu 693 17 expediting expedite VBG cord-014597-66vd2mdu 693 18 the the DT cord-014597-66vd2mdu 693 19 sample sample NN cord-014597-66vd2mdu 693 20 preparation preparation NN cord-014597-66vd2mdu 693 21 with with IN cord-014597-66vd2mdu 693 22 improved improved JJ cord-014597-66vd2mdu 693 23 consistency consistency NN cord-014597-66vd2mdu 693 24 ( ( -LRB- cord-014597-66vd2mdu 693 25 Fig Fig NNP cord-014597-66vd2mdu 693 26 . . . cord-014597-66vd2mdu 693 27 1c 1c CD cord-014597-66vd2mdu 693 28 ) ) -RRB- cord-014597-66vd2mdu 693 29 . . . cord-014597-66vd2mdu 694 1 Finally finally RB cord-014597-66vd2mdu 694 2 , , , cord-014597-66vd2mdu 694 3 implementing implement VBG cord-014597-66vd2mdu 694 4 the the DT cord-014597-66vd2mdu 694 5 liquid liquid JJ cord-014597-66vd2mdu 694 6 handler handler NN cord-014597-66vd2mdu 694 7 function function NN cord-014597-66vd2mdu 694 8 of of IN cord-014597-66vd2mdu 694 9 AMBR15 ambr15 NN cord-014597-66vd2mdu 694 10 to to TO cord-014597-66vd2mdu 694 11 support support VB cord-014597-66vd2mdu 694 12 media medium NNS cord-014597-66vd2mdu 694 13 and and CC cord-014597-66vd2mdu 694 14 feed feed NN cord-014597-66vd2mdu 694 15 formulation formulation NN cord-014597-66vd2mdu 694 16 significantly significantly RB cord-014597-66vd2mdu 694 17 reduced reduce VBD cord-014597-66vd2mdu 694 18 the the DT cord-014597-66vd2mdu 694 19 labor labor NN cord-014597-66vd2mdu 694 20 for for IN cord-014597-66vd2mdu 694 21 each each DT cord-014597-66vd2mdu 694 22 experiment experiment NN cord-014597-66vd2mdu 694 23 . . . cord-014597-66vd2mdu 695 1 Summary summary NN cord-014597-66vd2mdu 695 2 of of IN cord-014597-66vd2mdu 695 3 the the DT cord-014597-66vd2mdu 695 4 capability capability NN cord-014597-66vd2mdu 695 5 comparison comparison NN cord-014597-66vd2mdu 695 6 between between IN cord-014597-66vd2mdu 695 7 the the DT cord-014597-66vd2mdu 695 8 HTS HTS NNP cord-014597-66vd2mdu 695 9 platform platform NN cord-014597-66vd2mdu 695 10 and and CC cord-014597-66vd2mdu 695 11 the the DT cord-014597-66vd2mdu 695 12 traditional traditional JJ cord-014597-66vd2mdu 695 13 method method NN cord-014597-66vd2mdu 695 14 are be VBP cord-014597-66vd2mdu 695 15 listed list VBN cord-014597-66vd2mdu 695 16 in in IN cord-014597-66vd2mdu 695 17 Table Table NNP cord-014597-66vd2mdu 695 18 1 1 CD cord-014597-66vd2mdu 695 19 . . . cord-014597-66vd2mdu 696 1 A a DT cord-014597-66vd2mdu 696 2 case case NN cord-014597-66vd2mdu 696 3 study study NN cord-014597-66vd2mdu 696 4 of of IN cord-014597-66vd2mdu 696 5 a a DT cord-014597-66vd2mdu 696 6 complex complex JJ cord-014597-66vd2mdu 696 7 feed feed NN cord-014597-66vd2mdu 696 8 screening screening NN cord-014597-66vd2mdu 696 9 with with IN cord-014597-66vd2mdu 696 10 definitive definitive JJ cord-014597-66vd2mdu 696 11 screening screening NN cord-014597-66vd2mdu 696 12 design design NN cord-014597-66vd2mdu 696 13 was be VBD cord-014597-66vd2mdu 696 14 completed complete VBN cord-014597-66vd2mdu 696 15 using use VBG cord-014597-66vd2mdu 696 16 the the DT cord-014597-66vd2mdu 696 17 semi semi JJ cord-014597-66vd2mdu 696 18 - - JJ cord-014597-66vd2mdu 696 19 automatic automatic JJ cord-014597-66vd2mdu 696 20 HTS HTS NNP cord-014597-66vd2mdu 696 21 platform platform NN cord-014597-66vd2mdu 696 22 . . . cord-014597-66vd2mdu 697 1 This this DT cord-014597-66vd2mdu 697 2 experiment experiment NN cord-014597-66vd2mdu 697 3 , , , cord-014597-66vd2mdu 697 4 containing contain VBG cord-014597-66vd2mdu 697 5 more more JJR cord-014597-66vd2mdu 697 6 than than IN cord-014597-66vd2mdu 697 7 60 60 CD cord-014597-66vd2mdu 697 8 feed feed NN cord-014597-66vd2mdu 697 9 formulations formulation NNS cord-014597-66vd2mdu 697 10 in in IN cord-014597-66vd2mdu 697 11 duplicates duplicate NNS cord-014597-66vd2mdu 697 12 , , , cord-014597-66vd2mdu 697 13 was be VBD cord-014597-66vd2mdu 697 14 handled handle VBN cord-014597-66vd2mdu 697 15 by by IN cord-014597-66vd2mdu 697 16 one one CD cord-014597-66vd2mdu 697 17 operator operator NN cord-014597-66vd2mdu 697 18 and and CC cord-014597-66vd2mdu 697 19 delivered deliver VBD cord-014597-66vd2mdu 697 20 a a DT cord-014597-66vd2mdu 697 21 40 40 CD cord-014597-66vd2mdu 697 22 % % NN cord-014597-66vd2mdu 697 23 improvement improvement NN cord-014597-66vd2mdu 697 24 in in IN cord-014597-66vd2mdu 697 25 productivity productivity NN cord-014597-66vd2mdu 697 26 within within IN cord-014597-66vd2mdu 697 27 a a DT cord-014597-66vd2mdu 697 28 4 4 CD cord-014597-66vd2mdu 697 29 week week NN cord-014597-66vd2mdu 697 30 period period NN cord-014597-66vd2mdu 697 31 ( ( -LRB- cord-014597-66vd2mdu 697 32 Data Data NNP cord-014597-66vd2mdu 697 33 not not RB cord-014597-66vd2mdu 697 34 shown show VBN cord-014597-66vd2mdu 697 35 ) ) -RRB- cord-014597-66vd2mdu 697 36 . . . cord-014597-66vd2mdu 698 1 In in IN cord-014597-66vd2mdu 698 2 addition addition NN cord-014597-66vd2mdu 698 3 , , , cord-014597-66vd2mdu 698 4 implementing implement VBG cord-014597-66vd2mdu 698 5 the the DT cord-014597-66vd2mdu 698 6 HTS HTS NNP cord-014597-66vd2mdu 698 7 platform platform NN cord-014597-66vd2mdu 698 8 for for IN cord-014597-66vd2mdu 698 9 this this DT cord-014597-66vd2mdu 698 10 study study NN cord-014597-66vd2mdu 698 11 also also RB cord-014597-66vd2mdu 698 12 resulted result VBD cord-014597-66vd2mdu 698 13 into~80 into~80 NNP cord-014597-66vd2mdu 698 14 % % NN cord-014597-66vd2mdu 698 15 reduction reduction NN cord-014597-66vd2mdu 698 16 in in IN cord-014597-66vd2mdu 698 17 labor labor NN cord-014597-66vd2mdu 698 18 while while IN cord-014597-66vd2mdu 698 19 improving improve VBG cord-014597-66vd2mdu 698 20 the the DT cord-014597-66vd2mdu 698 21 traceability traceability NN cord-014597-66vd2mdu 698 22 of of IN cord-014597-66vd2mdu 698 23 formulation formulation NN cord-014597-66vd2mdu 698 24 preparation preparation NN cord-014597-66vd2mdu 698 25 . . . cord-014597-66vd2mdu 699 1 A a DT cord-014597-66vd2mdu 699 2 semi semi RB cord-014597-66vd2mdu 699 3 - - JJ cord-014597-66vd2mdu 699 4 automated automated JJ cord-014597-66vd2mdu 699 5 HTS HTS NNP cord-014597-66vd2mdu 699 6 platform platform NN cord-014597-66vd2mdu 699 7 was be VBD cord-014597-66vd2mdu 699 8 developed develop VBN cord-014597-66vd2mdu 699 9 to to TO cord-014597-66vd2mdu 699 10 support support VB cord-014597-66vd2mdu 699 11 media medium NNS cord-014597-66vd2mdu 699 12 and and CC cord-014597-66vd2mdu 699 13 feeds feed VBZ cord-014597-66vd2mdu 699 14 screening screening NN cord-014597-66vd2mdu 699 15 and and CC cord-014597-66vd2mdu 699 16 development development NN cord-014597-66vd2mdu 699 17 for for IN cord-014597-66vd2mdu 699 18 early early JJ cord-014597-66vd2mdu 699 19 stage stage NN cord-014597-66vd2mdu 699 20 biologics biologic NNS cord-014597-66vd2mdu 699 21 projects project NNS cord-014597-66vd2mdu 699 22 . . . cord-014597-66vd2mdu 700 1 The the DT cord-014597-66vd2mdu 700 2 platform platform NN cord-014597-66vd2mdu 700 3 utilizes utilize VBZ cord-014597-66vd2mdu 700 4 24 24 CD cord-014597-66vd2mdu 700 5 DWPs dwp NNS cord-014597-66vd2mdu 700 6 , , , cord-014597-66vd2mdu 700 7 NyONE NyONE NNP cord-014597-66vd2mdu 700 8 cell cell NN cord-014597-66vd2mdu 700 9 imager imager NN cord-014597-66vd2mdu 700 10 , , . cord-014597-66vd2mdu 701 1 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 701 2 , , , cord-014597-66vd2mdu 701 3 Freedom Freedom NNP cord-014597-66vd2mdu 701 4 EVO EVO NNP cord-014597-66vd2mdu 701 5 liquid liquid JJ cord-014597-66vd2mdu 701 6 handler handler NN cord-014597-66vd2mdu 701 7 system system NN cord-014597-66vd2mdu 701 8 , , , cord-014597-66vd2mdu 701 9 and and CC cord-014597-66vd2mdu 701 10 BioHT BioHT NNP cord-014597-66vd2mdu 701 11 metabolic metabolic JJ cord-014597-66vd2mdu 701 12 analyzer analyzer NN cord-014597-66vd2mdu 701 13 to to TO cord-014597-66vd2mdu 701 14 accelerate accelerate VB cord-014597-66vd2mdu 701 15 the the DT cord-014597-66vd2mdu 701 16 screening screening NN cord-014597-66vd2mdu 701 17 process process NN cord-014597-66vd2mdu 701 18 . . . cord-014597-66vd2mdu 702 1 This this DT cord-014597-66vd2mdu 702 2 screening screening NN cord-014597-66vd2mdu 702 3 platform platform NN cord-014597-66vd2mdu 702 4 not not RB cord-014597-66vd2mdu 702 5 only only RB cord-014597-66vd2mdu 702 6 improves improve VBZ cord-014597-66vd2mdu 702 7 process process NN cord-014597-66vd2mdu 702 8 throughput throughput NN cord-014597-66vd2mdu 702 9 , , , cord-014597-66vd2mdu 702 10 operational operational JJ cord-014597-66vd2mdu 702 11 precision precision NN cord-014597-66vd2mdu 702 12 , , , cord-014597-66vd2mdu 702 13 and and CC cord-014597-66vd2mdu 702 14 traceability traceability NN cord-014597-66vd2mdu 702 15 of of IN cord-014597-66vd2mdu 702 16 formulation formulation NN cord-014597-66vd2mdu 702 17 preparation preparation NN cord-014597-66vd2mdu 702 18 , , , cord-014597-66vd2mdu 702 19 but but CC cord-014597-66vd2mdu 702 20 also also RB cord-014597-66vd2mdu 702 21 reduces reduce VBZ cord-014597-66vd2mdu 702 22 the the DT cord-014597-66vd2mdu 702 23 labor labor NN cord-014597-66vd2mdu 702 24 for for IN cord-014597-66vd2mdu 702 25 the the DT cord-014597-66vd2mdu 702 26 media medium NNS cord-014597-66vd2mdu 702 27 and and CC cord-014597-66vd2mdu 702 28 feed feed NN cord-014597-66vd2mdu 702 29 formulation formulation NN cord-014597-66vd2mdu 702 30 preparation preparation NN cord-014597-66vd2mdu 702 31 . . . cord-014597-66vd2mdu 703 1 Background background VB cord-014597-66vd2mdu 703 2 A a DT cord-014597-66vd2mdu 703 3 perfusion perfusion NN cord-014597-66vd2mdu 703 4 medium medium NN cord-014597-66vd2mdu 703 5 requires require VBZ cord-014597-66vd2mdu 703 6 high high JJ cord-014597-66vd2mdu 703 7 concentrations concentration NNS cord-014597-66vd2mdu 703 8 of of IN cord-014597-66vd2mdu 703 9 specific specific JJ cord-014597-66vd2mdu 703 10 nutrients nutrient NNS cord-014597-66vd2mdu 703 11 while while IN cord-014597-66vd2mdu 703 12 balancing balance VBG cord-014597-66vd2mdu 703 13 other other JJ cord-014597-66vd2mdu 703 14 components component NNS cord-014597-66vd2mdu 703 15 to to TO cord-014597-66vd2mdu 703 16 support support VB cord-014597-66vd2mdu 703 17 intensified intensify VBN cord-014597-66vd2mdu 703 18 perfusion perfusion NN cord-014597-66vd2mdu 703 19 processes process NNS cord-014597-66vd2mdu 703 20 . . . cord-014597-66vd2mdu 704 1 Using use VBG cord-014597-66vd2mdu 704 2 a a DT cord-014597-66vd2mdu 704 3 combination combination NN cord-014597-66vd2mdu 704 4 of of IN cord-014597-66vd2mdu 704 5 design design NN cord-014597-66vd2mdu 704 6 of of IN cord-014597-66vd2mdu 704 7 experiment experiment NN cord-014597-66vd2mdu 704 8 ( ( -LRB- cord-014597-66vd2mdu 704 9 DOE DOE NNP cord-014597-66vd2mdu 704 10 ) ) -RRB- cord-014597-66vd2mdu 704 11 , , , cord-014597-66vd2mdu 704 12 multivariate multivariate JJ cord-014597-66vd2mdu 704 13 analysis analysis NN cord-014597-66vd2mdu 704 14 ( ( -LRB- cord-014597-66vd2mdu 704 15 MVA MVA NNP cord-014597-66vd2mdu 704 16 ) ) -RRB- cord-014597-66vd2mdu 704 17 , , , cord-014597-66vd2mdu 704 18 and and CC cord-014597-66vd2mdu 704 19 spent spend VBD cord-014597-66vd2mdu 704 20 media medium NNS cord-014597-66vd2mdu 704 21 analysis analysis NN cord-014597-66vd2mdu 704 22 , , , cord-014597-66vd2mdu 704 23 we -PRON- PRP cord-014597-66vd2mdu 704 24 developed develop VBD cord-014597-66vd2mdu 704 25 a a DT cord-014597-66vd2mdu 704 26 catalog catalog NN cord-014597-66vd2mdu 704 27 " " `` cord-014597-66vd2mdu 704 28 de de FW cord-014597-66vd2mdu 704 29 novo novo NN cord-014597-66vd2mdu 704 30 " " '' cord-014597-66vd2mdu 704 31 perfusion perfusion NN cord-014597-66vd2mdu 704 32 medium medium NN cord-014597-66vd2mdu 704 33 by by IN cord-014597-66vd2mdu 704 34 working work VBG cord-014597-66vd2mdu 704 35 with with IN cord-014597-66vd2mdu 704 36 multiple multiple JJ cord-014597-66vd2mdu 704 37 CHO CHO NNP cord-014597-66vd2mdu 704 38 cell cell NN cord-014597-66vd2mdu 704 39 lines line NNS cord-014597-66vd2mdu 704 40 and and CC cord-014597-66vd2mdu 704 41 proteins protein NNS cord-014597-66vd2mdu 704 42 . . . cord-014597-66vd2mdu 705 1 The the DT cord-014597-66vd2mdu 705 2 optimization optimization NN cord-014597-66vd2mdu 705 3 of of IN cord-014597-66vd2mdu 705 4 the the DT cord-014597-66vd2mdu 705 5 medium medium NN cord-014597-66vd2mdu 705 6 in in IN cord-014597-66vd2mdu 705 7 bioreactors bioreactor NNS cord-014597-66vd2mdu 705 8 using use VBG cord-014597-66vd2mdu 705 9 alternating alternate VBG cord-014597-66vd2mdu 705 10 tangential tangential JJ cord-014597-66vd2mdu 705 11 flow flow NN cord-014597-66vd2mdu 705 12 ( ( -LRB- cord-014597-66vd2mdu 705 13 ATF ATF NNP cord-014597-66vd2mdu 705 14 ) ) -RRB- cord-014597-66vd2mdu 705 15 cell cell NN cord-014597-66vd2mdu 705 16 retention retention NN cord-014597-66vd2mdu 705 17 devices device NNS cord-014597-66vd2mdu 705 18 reduced reduce VBD cord-014597-66vd2mdu 705 19 the the DT cord-014597-66vd2mdu 705 20 minimum minimum NN cord-014597-66vd2mdu 705 21 CSPR CSPR NNP cord-014597-66vd2mdu 705 22 from from IN cord-014597-66vd2mdu 705 23 over over IN cord-014597-66vd2mdu 705 24 80pL 80pl CD cord-014597-66vd2mdu 705 25 / / SYM cord-014597-66vd2mdu 705 26 cell cell NN cord-014597-66vd2mdu 705 27 / / SYM cord-014597-66vd2mdu 705 28 d d NN cord-014597-66vd2mdu 705 29 to to IN cord-014597-66vd2mdu 705 30 under under IN cord-014597-66vd2mdu 705 31 35pL 35pl CD cord-014597-66vd2mdu 705 32 / / SYM cord-014597-66vd2mdu 705 33 cell cell NN cord-014597-66vd2mdu 705 34 / / SYM cord-014597-66vd2mdu 705 35 d d NN cord-014597-66vd2mdu 705 36 for for IN cord-014597-66vd2mdu 705 37 most most JJS cord-014597-66vd2mdu 705 38 cell cell NN cord-014597-66vd2mdu 705 39 lines line NNS cord-014597-66vd2mdu 705 40 while while IN cord-014597-66vd2mdu 705 41 increasing increase VBG cord-014597-66vd2mdu 705 42 specific specific JJ cord-014597-66vd2mdu 705 43 productivity productivity NN cord-014597-66vd2mdu 705 44 during during IN cord-014597-66vd2mdu 705 45 30 30 CD cord-014597-66vd2mdu 705 46 day day NN cord-014597-66vd2mdu 705 47 steady steady JJ cord-014597-66vd2mdu 705 48 states state NNS cord-014597-66vd2mdu 705 49 with with IN cord-014597-66vd2mdu 705 50 stable stable JJ cord-014597-66vd2mdu 705 51 growth growth NN cord-014597-66vd2mdu 705 52 rates rate NNS cord-014597-66vd2mdu 705 53 , , , cord-014597-66vd2mdu 705 54 viability viability NN cord-014597-66vd2mdu 705 55 , , , cord-014597-66vd2mdu 705 56 volumetric volumetric JJ cord-014597-66vd2mdu 705 57 productivity productivity NN cord-014597-66vd2mdu 705 58 and and CC cord-014597-66vd2mdu 705 59 product product NN cord-014597-66vd2mdu 705 60 quality quality NN cord-014597-66vd2mdu 705 61 . . . cord-014597-66vd2mdu 706 1 High high JJ cord-014597-66vd2mdu 706 2 Throughput Throughput NNP cord-014597-66vd2mdu 706 3 Screening Screening NNP cord-014597-66vd2mdu 706 4 ( ( -LRB- cord-014597-66vd2mdu 706 5 HTS HTS NNP cord-014597-66vd2mdu 706 6 ) ) -RRB- cord-014597-66vd2mdu 706 7 was be VBD cord-014597-66vd2mdu 706 8 performed perform VBN cord-014597-66vd2mdu 706 9 with with IN cord-014597-66vd2mdu 706 10 seven seven CD cord-014597-66vd2mdu 706 11 cell cell NN cord-014597-66vd2mdu 706 12 lines line NNS cord-014597-66vd2mdu 706 13 , , , cord-014597-66vd2mdu 706 14 while while IN cord-014597-66vd2mdu 706 15 four four CD cord-014597-66vd2mdu 706 16 were be VBD cord-014597-66vd2mdu 706 17 used use VBN cord-014597-66vd2mdu 706 18 in in IN cord-014597-66vd2mdu 706 19 bioreactors bioreactor NNS cord-014597-66vd2mdu 706 20 : : : cord-014597-66vd2mdu 706 21 CHO CHO NNP cord-014597-66vd2mdu 706 22 - - HYPH cord-014597-66vd2mdu 706 23 S S NNP cord-014597-66vd2mdu 706 24 , , , cord-014597-66vd2mdu 706 25 DG44 DG44 NNP cord-014597-66vd2mdu 706 26 , , , cord-014597-66vd2mdu 706 27 and and CC cord-014597-66vd2mdu 706 28 two two CD cord-014597-66vd2mdu 706 29 CHOZN CHOZN NNP cord-014597-66vd2mdu 706 30 ® ® NNPS cord-014597-66vd2mdu 706 31 GS GS NNP cord-014597-66vd2mdu 706 32 lines line NNS cord-014597-66vd2mdu 706 33 , , , cord-014597-66vd2mdu 706 34 each each DT cord-014597-66vd2mdu 706 35 producing produce VBG cord-014597-66vd2mdu 706 36 different different JJ cord-014597-66vd2mdu 706 37 monoclonal monoclonal JJ cord-014597-66vd2mdu 706 38 antibodies antibody NNS cord-014597-66vd2mdu 706 39 and and CC cord-014597-66vd2mdu 706 40 include include VBP cord-014597-66vd2mdu 706 41 a a DT cord-014597-66vd2mdu 706 42 fusion fusion NN cord-014597-66vd2mdu 706 43 protein protein NN cord-014597-66vd2mdu 706 44 . . . cord-014597-66vd2mdu 707 1 For for IN cord-014597-66vd2mdu 707 2 HTS HTS NNP cord-014597-66vd2mdu 707 3 experiments experiment NNS cord-014597-66vd2mdu 707 4 , , , cord-014597-66vd2mdu 707 5 cells cell NNS cord-014597-66vd2mdu 707 6 were be VBD cord-014597-66vd2mdu 707 7 inoculated inoculate VBN cord-014597-66vd2mdu 707 8 at at IN cord-014597-66vd2mdu 707 9 2.0x10 2.0x10 CD cord-014597-66vd2mdu 707 10 6 6 CD cord-014597-66vd2mdu 707 11 vc vc NNP cord-014597-66vd2mdu 707 12 / / SYM cord-014597-66vd2mdu 707 13 mL ml NN cord-014597-66vd2mdu 707 14 with with IN cord-014597-66vd2mdu 707 15 a a DT cord-014597-66vd2mdu 707 16 30 30 CD cord-014597-66vd2mdu 707 17 mL ml NN cord-014597-66vd2mdu 707 18 working working NN cord-014597-66vd2mdu 707 19 volume volume NN cord-014597-66vd2mdu 707 20 in in IN cord-014597-66vd2mdu 707 21 50 50 CD cord-014597-66vd2mdu 707 22 mL ml NN cord-014597-66vd2mdu 707 23 TPP TPP NNP cord-014597-66vd2mdu 707 24 ® ® VBP cord-014597-66vd2mdu 707 25 tubes tube NNS cord-014597-66vd2mdu 707 26 and and CC cord-014597-66vd2mdu 707 27 cultured culture VBN cord-014597-66vd2mdu 707 28 for for IN cord-014597-66vd2mdu 707 29 7 7 CD cord-014597-66vd2mdu 707 30 days day NNS cord-014597-66vd2mdu 707 31 in in IN cord-014597-66vd2mdu 707 32 a a DT cord-014597-66vd2mdu 707 33 Multitron Multitron NNP cord-014597-66vd2mdu 707 34 shaken shake VBN cord-014597-66vd2mdu 707 35 at at IN cord-014597-66vd2mdu 707 36 200rpm 200rpm CD cord-014597-66vd2mdu 707 37 , , , cord-014597-66vd2mdu 707 38 37 37 CD cord-014597-66vd2mdu 707 39 ° ° NN cord-014597-66vd2mdu 707 40 C c NN cord-014597-66vd2mdu 707 41 , , , cord-014597-66vd2mdu 707 42 80 80 CD cord-014597-66vd2mdu 707 43 % % NN cord-014597-66vd2mdu 707 44 RH RH NNP cord-014597-66vd2mdu 707 45 , , , cord-014597-66vd2mdu 707 46 and and CC cord-014597-66vd2mdu 707 47 5 5 CD cord-014597-66vd2mdu 707 48 % % NN cord-014597-66vd2mdu 707 49 CO co NN cord-014597-66vd2mdu 707 50 2 2 CD cord-014597-66vd2mdu 707 51 . . . cord-014597-66vd2mdu 708 1 For for IN cord-014597-66vd2mdu 708 2 benchtop benchtop NN cord-014597-66vd2mdu 708 3 perfusion perfusion NN cord-014597-66vd2mdu 708 4 , , , cord-014597-66vd2mdu 708 5 cells cell NNS cord-014597-66vd2mdu 708 6 were be VBD cord-014597-66vd2mdu 708 7 inoculated inoculate VBN cord-014597-66vd2mdu 708 8 at at IN cord-014597-66vd2mdu 708 9 0.4 0.4 CD cord-014597-66vd2mdu 708 10 - - SYM cord-014597-66vd2mdu 708 11 2.0x10 2.0x10 CD cord-014597-66vd2mdu 708 12 6 6 CD cord-014597-66vd2mdu 708 13 vc vc NNP cord-014597-66vd2mdu 708 14 / / SYM cord-014597-66vd2mdu 708 15 mL ml NN cord-014597-66vd2mdu 708 16 in in IN cord-014597-66vd2mdu 708 17 3L 3l CD cord-014597-66vd2mdu 708 18 Applikon Applikon NNP cord-014597-66vd2mdu 708 19 bioreactors bioreactor NNS cord-014597-66vd2mdu 708 20 ( ( -LRB- cord-014597-66vd2mdu 708 21 Applikon Applikon NNP cord-014597-66vd2mdu 708 22 , , , cord-014597-66vd2mdu 708 23 Netherlands Netherlands NNP cord-014597-66vd2mdu 708 24 ) ) -RRB- cord-014597-66vd2mdu 708 25 with with IN cord-014597-66vd2mdu 708 26 a a DT cord-014597-66vd2mdu 708 27 2L 2l NN cord-014597-66vd2mdu 708 28 working working NN cord-014597-66vd2mdu 708 29 volume volume NN cord-014597-66vd2mdu 708 30 . . . cord-014597-66vd2mdu 709 1 Bioreactors bioreactor NNS cord-014597-66vd2mdu 709 2 were be VBD cord-014597-66vd2mdu 709 3 operated operate VBN cord-014597-66vd2mdu 709 4 at at IN cord-014597-66vd2mdu 709 5 350 350 CD cord-014597-66vd2mdu 709 6 rpm rpm NN cord-014597-66vd2mdu 709 7 , , , cord-014597-66vd2mdu 709 8 37 37 CD cord-014597-66vd2mdu 709 9 ° ° NN cord-014597-66vd2mdu 709 10 C c NN cord-014597-66vd2mdu 709 11 , , , cord-014597-66vd2mdu 709 12 40 40 CD cord-014597-66vd2mdu 709 13 % % NN cord-014597-66vd2mdu 709 14 DO DO NNP cord-014597-66vd2mdu 709 15 , , , cord-014597-66vd2mdu 709 16 and and CC cord-014597-66vd2mdu 709 17 a a DT cord-014597-66vd2mdu 709 18 pH ph NN cord-014597-66vd2mdu 709 19 of of IN cord-014597-66vd2mdu 710 1 6.9 6.9 CD cord-014597-66vd2mdu 710 2 or or CC cord-014597-66vd2mdu 710 3 7.1±0.05 7.1±0.05 CD cord-014597-66vd2mdu 710 4 depending depend VBG cord-014597-66vd2mdu 710 5 on on IN cord-014597-66vd2mdu 710 6 the the DT cord-014597-66vd2mdu 710 7 cell cell NN cord-014597-66vd2mdu 710 8 line line NN cord-014597-66vd2mdu 710 9 . . . cord-014597-66vd2mdu 711 1 Oxygen oxygen NN cord-014597-66vd2mdu 711 2 was be VBD cord-014597-66vd2mdu 711 3 supplied supply VBN cord-014597-66vd2mdu 711 4 through through IN cord-014597-66vd2mdu 711 5 an an DT cord-014597-66vd2mdu 711 6 L l NN cord-014597-66vd2mdu 711 7 - - HYPH cord-014597-66vd2mdu 711 8 sparger sparger NN cord-014597-66vd2mdu 711 9 or or CC cord-014597-66vd2mdu 711 10 microsparger microsparger NN cord-014597-66vd2mdu 711 11 as as IN cord-014597-66vd2mdu 711 12 needed need VBN cord-014597-66vd2mdu 711 13 , , , cord-014597-66vd2mdu 711 14 and and CC cord-014597-66vd2mdu 711 15 Excell Excell NNP cord-014597-66vd2mdu 711 16 ® ® POS cord-014597-66vd2mdu 711 17 antifoam antifoam NNP cord-014597-66vd2mdu 711 18 ( ( -LRB- cord-014597-66vd2mdu 711 19 MilliporeSigma MilliporeSigma NNP cord-014597-66vd2mdu 711 20 , , , cord-014597-66vd2mdu 711 21 Germany Germany NNP cord-014597-66vd2mdu 711 22 ) ) -RRB- cord-014597-66vd2mdu 711 23 was be VBD cord-014597-66vd2mdu 711 24 added add VBN cord-014597-66vd2mdu 711 25 at at IN cord-014597-66vd2mdu 711 26 a a DT cord-014597-66vd2mdu 711 27 maximum maximum JJ cord-014597-66vd2mdu 711 28 rate rate NN cord-014597-66vd2mdu 711 29 of of IN cord-014597-66vd2mdu 711 30 0.25 0.25 CD cord-014597-66vd2mdu 711 31 % % NN cord-014597-66vd2mdu 711 32 v v NN cord-014597-66vd2mdu 711 33 / / SYM cord-014597-66vd2mdu 711 34 v v NN cord-014597-66vd2mdu 711 35 to to TO cord-014597-66vd2mdu 711 36 control control VB cord-014597-66vd2mdu 711 37 foam foam NN cord-014597-66vd2mdu 711 38 . . . cord-014597-66vd2mdu 712 1 At at IN cord-014597-66vd2mdu 712 2 a a DT cord-014597-66vd2mdu 712 3 cell cell NN cord-014597-66vd2mdu 712 4 concentration concentration NN cord-014597-66vd2mdu 712 5 of~6.0x10 of~6.0x10 NNP cord-014597-66vd2mdu 712 6 6 6 CD cord-014597-66vd2mdu 712 7 vc vc NNP cord-014597-66vd2mdu 712 8 / / SYM cord-014597-66vd2mdu 712 9 mL ml NN cord-014597-66vd2mdu 712 10 , , , cord-014597-66vd2mdu 712 11 perfusion perfusion NN cord-014597-66vd2mdu 712 12 was be VBD cord-014597-66vd2mdu 712 13 initiated initiate VBN cord-014597-66vd2mdu 712 14 using use VBG cord-014597-66vd2mdu 712 15 the the DT cord-014597-66vd2mdu 712 16 ATF2 ATF2 NNP cord-014597-66vd2mdu 712 17 ( ( -LRB- cord-014597-66vd2mdu 712 18 RepliGen RepliGen NNP cord-014597-66vd2mdu 712 19 , , , cord-014597-66vd2mdu 712 20 Massachusetts Massachusetts NNP cord-014597-66vd2mdu 712 21 ) ) -RRB- cord-014597-66vd2mdu 712 22 , , , cord-014597-66vd2mdu 712 23 with with IN cord-014597-66vd2mdu 712 24 a a DT cord-014597-66vd2mdu 712 25 bleed bleed NN cord-014597-66vd2mdu 712 26 set set VBN cord-014597-66vd2mdu 712 27 to to TO cord-014597-66vd2mdu 712 28 maintain maintain VB cord-014597-66vd2mdu 712 29 cell cell NN cord-014597-66vd2mdu 712 30 concentrations concentration NNS cord-014597-66vd2mdu 712 31 at at IN cord-014597-66vd2mdu 712 32 50 50 CD cord-014597-66vd2mdu 712 33 or or CC cord-014597-66vd2mdu 712 34 80 80 CD cord-014597-66vd2mdu 712 35 * * SYM cord-014597-66vd2mdu 712 36 10 10 CD cord-014597-66vd2mdu 712 37 6 6 CD cord-014597-66vd2mdu 712 38 vc vc NNP cord-014597-66vd2mdu 712 39 / / SYM cord-014597-66vd2mdu 712 40 mL. mL. NNP cord-014597-66vd2mdu 712 41 Two two CD cord-014597-66vd2mdu 712 42 " " `` cord-014597-66vd2mdu 712 43 de de FW cord-014597-66vd2mdu 712 44 novo novo NNP cord-014597-66vd2mdu 712 45 " " '' cord-014597-66vd2mdu 712 46 prototype prototype NN cord-014597-66vd2mdu 712 47 media medium NNS cord-014597-66vd2mdu 712 48 were be VBD cord-014597-66vd2mdu 712 49 developed develop VBN cord-014597-66vd2mdu 712 50 using use VBG cord-014597-66vd2mdu 712 51 DOE DOE NNP cord-014597-66vd2mdu 712 52 and and CC cord-014597-66vd2mdu 712 53 MVA MVA NNP cord-014597-66vd2mdu 712 54 in in IN cord-014597-66vd2mdu 712 55 HTS HTS NNP cord-014597-66vd2mdu 712 56 with with IN cord-014597-66vd2mdu 712 57 TPPs tpp NNS cord-014597-66vd2mdu 712 58 and and CC cord-014597-66vd2mdu 712 59 an an DT cord-014597-66vd2mdu 712 60 ambr ambr NN cord-014597-66vd2mdu 712 61 ® ® NN cord-014597-66vd2mdu 712 62 15 15 CD cord-014597-66vd2mdu 712 63 [ [ -LRB- cord-014597-66vd2mdu 712 64 1 1 CD cord-014597-66vd2mdu 712 65 ] ] -RRB- cord-014597-66vd2mdu 712 66 and and CC cord-014597-66vd2mdu 712 67 one one PRP cord-014597-66vd2mdu 712 68 was be VBD cord-014597-66vd2mdu 712 69 chosen choose VBN cord-014597-66vd2mdu 712 70 for for IN cord-014597-66vd2mdu 712 71 further further JJ cord-014597-66vd2mdu 712 72 development development NN cord-014597-66vd2mdu 712 73 after after IN cord-014597-66vd2mdu 712 74 comparing compare VBG cord-014597-66vd2mdu 712 75 to to IN cord-014597-66vd2mdu 712 76 a a DT cord-014597-66vd2mdu 712 77 basal basal NN cord-014597-66vd2mdu 712 78 medium medium NN cord-014597-66vd2mdu 712 79 enriched enrich VBN cord-014597-66vd2mdu 712 80 with with IN cord-014597-66vd2mdu 712 81 feed feed NN cord-014597-66vd2mdu 712 82 in in IN cord-014597-66vd2mdu 712 83 bioreactors bioreactor NNS cord-014597-66vd2mdu 712 84 . . . cord-014597-66vd2mdu 713 1 Eleven eleven CD cord-014597-66vd2mdu 713 2 components component NNS cord-014597-66vd2mdu 713 3 were be VBD cord-014597-66vd2mdu 713 4 identified identify VBN cord-014597-66vd2mdu 713 5 as as IN cord-014597-66vd2mdu 713 6 significant significant JJ cord-014597-66vd2mdu 713 7 effectors effector NNS cord-014597-66vd2mdu 713 8 of of IN cord-014597-66vd2mdu 713 9 critical critical JJ cord-014597-66vd2mdu 713 10 parameters parameter NNS cord-014597-66vd2mdu 713 11 for for IN cord-014597-66vd2mdu 713 12 perfusion perfusion NN cord-014597-66vd2mdu 713 13 processes process NNS cord-014597-66vd2mdu 713 14 across across IN cord-014597-66vd2mdu 713 15 evaluated evaluate VBN cord-014597-66vd2mdu 713 16 cell cell NN cord-014597-66vd2mdu 713 17 lines line NNS cord-014597-66vd2mdu 713 18 . . . cord-014597-66vd2mdu 714 1 DOE DOE NNP cord-014597-66vd2mdu 714 2 central central JJ cord-014597-66vd2mdu 714 3 composite composite JJ cord-014597-66vd2mdu 714 4 experiments experiment NNS cord-014597-66vd2mdu 714 5 were be VBD cord-014597-66vd2mdu 714 6 run run VBN cord-014597-66vd2mdu 714 7 and and CC cord-014597-66vd2mdu 714 8 component component NN cord-014597-66vd2mdu 714 9 concentrations concentration NNS cord-014597-66vd2mdu 714 10 were be VBD cord-014597-66vd2mdu 714 11 optimized optimize VBN cord-014597-66vd2mdu 714 12 in in IN cord-014597-66vd2mdu 714 13 the the DT cord-014597-66vd2mdu 714 14 selected select VBN cord-014597-66vd2mdu 714 15 prototype prototype NN cord-014597-66vd2mdu 714 16 . . . cord-014597-66vd2mdu 715 1 In in IN cord-014597-66vd2mdu 715 2 parallel parallel JJ cord-014597-66vd2mdu 715 3 , , , cord-014597-66vd2mdu 715 4 amino amino NN cord-014597-66vd2mdu 715 5 acid acid NN cord-014597-66vd2mdu 715 6 specific specific JJ cord-014597-66vd2mdu 715 7 consumption consumption NN cord-014597-66vd2mdu 715 8 rates rate NNS cord-014597-66vd2mdu 715 9 were be VBD cord-014597-66vd2mdu 715 10 calculated calculate VBN cord-014597-66vd2mdu 715 11 from from IN cord-014597-66vd2mdu 715 12 bioreactor bioreactor NN cord-014597-66vd2mdu 715 13 spent spend VBN cord-014597-66vd2mdu 715 14 media medium NNS cord-014597-66vd2mdu 715 15 samples sample NNS cord-014597-66vd2mdu 715 16 and and CC cord-014597-66vd2mdu 715 17 used use VBD cord-014597-66vd2mdu 715 18 to to TO cord-014597-66vd2mdu 715 19 adjust adjust VB cord-014597-66vd2mdu 715 20 the the DT cord-014597-66vd2mdu 715 21 concentration concentration NN cord-014597-66vd2mdu 715 22 of of IN cord-014597-66vd2mdu 715 23 amino amino JJ cord-014597-66vd2mdu 715 24 acids acid NNS cord-014597-66vd2mdu 715 25 to to TO cord-014597-66vd2mdu 715 26 target target VB cord-014597-66vd2mdu 715 27 a a DT cord-014597-66vd2mdu 715 28 reduced reduce VBN cord-014597-66vd2mdu 715 29 CSPR CSPR NNP cord-014597-66vd2mdu 715 30 . . . cord-014597-66vd2mdu 716 1 Increasing increase VBG cord-014597-66vd2mdu 716 2 specific specific JJ cord-014597-66vd2mdu 716 3 amino amino NN cord-014597-66vd2mdu 716 4 acids acid NNS cord-014597-66vd2mdu 716 5 concentrations concentration NNS cord-014597-66vd2mdu 716 6 resulted result VBD cord-014597-66vd2mdu 716 7 in in IN cord-014597-66vd2mdu 716 8 a a DT cord-014597-66vd2mdu 716 9 significant significant JJ cord-014597-66vd2mdu 716 10 reduction reduction NN cord-014597-66vd2mdu 716 11 of of IN cord-014597-66vd2mdu 716 12 the the DT cord-014597-66vd2mdu 716 13 minimum minimum NN cord-014597-66vd2mdu 716 14 CSPR CSPR NNP cord-014597-66vd2mdu 716 15 across across IN cord-014597-66vd2mdu 716 16 all all DT cord-014597-66vd2mdu 716 17 tested test VBN cord-014597-66vd2mdu 716 18 cell cell NN cord-014597-66vd2mdu 716 19 lines line NNS cord-014597-66vd2mdu 716 20 -for -for . cord-014597-66vd2mdu 717 1 example example NN cord-014597-66vd2mdu 718 1 the the DT cord-014597-66vd2mdu 718 2 CSPR CSPR NNP cord-014597-66vd2mdu 718 3 of of IN cord-014597-66vd2mdu 718 4 CHO CHO NNP cord-014597-66vd2mdu 718 5 - - HYPH cord-014597-66vd2mdu 718 6 S S NNP cord-014597-66vd2mdu 718 7 was be VBD cord-014597-66vd2mdu 718 8 reduced reduce VBN cord-014597-66vd2mdu 718 9 from from IN cord-014597-66vd2mdu 718 10 60 60 CD cord-014597-66vd2mdu 718 11 to to IN cord-014597-66vd2mdu 718 12 39pL 39pl CD cord-014597-66vd2mdu 718 13 / / SYM cord-014597-66vd2mdu 718 14 cell cell NN cord-014597-66vd2mdu 718 15 / / SYM cord-014597-66vd2mdu 718 16 day day NN cord-014597-66vd2mdu 718 17 ( ( -LRB- cord-014597-66vd2mdu 718 18 Table Table NNP cord-014597-66vd2mdu 718 19 1 1 CD cord-014597-66vd2mdu 718 20 ) ) -RRB- cord-014597-66vd2mdu 718 21 . . . cord-014597-66vd2mdu 719 1 However however RB cord-014597-66vd2mdu 719 2 , , , cord-014597-66vd2mdu 719 3 even even RB cord-014597-66vd2mdu 719 4 at at IN cord-014597-66vd2mdu 719 5 the the DT cord-014597-66vd2mdu 719 6 lower low JJR cord-014597-66vd2mdu 719 7 CSPR CSPR NNP cord-014597-66vd2mdu 719 8 , , , cord-014597-66vd2mdu 719 9 spent spend VBD cord-014597-66vd2mdu 719 10 media medium NNS cord-014597-66vd2mdu 719 11 analysis analysis NN cord-014597-66vd2mdu 719 12 revealed reveal VBD cord-014597-66vd2mdu 719 13 excess excess JJ cord-014597-66vd2mdu 719 14 concentration concentration NN cord-014597-66vd2mdu 719 15 of of IN cord-014597-66vd2mdu 719 16 some some DT cord-014597-66vd2mdu 719 17 amino amino NN cord-014597-66vd2mdu 719 18 acids acid NNS cord-014597-66vd2mdu 719 19 , , , cord-014597-66vd2mdu 719 20 so so RB cord-014597-66vd2mdu 719 21 specific specific JJ cord-014597-66vd2mdu 719 22 accumulating accumulate VBG cord-014597-66vd2mdu 719 23 amino amino NN cord-014597-66vd2mdu 719 24 acids acid NNS cord-014597-66vd2mdu 719 25 were be VBD cord-014597-66vd2mdu 719 26 reduced reduce VBN cord-014597-66vd2mdu 719 27 and and CC cord-014597-66vd2mdu 719 28 components component NNS cord-014597-66vd2mdu 719 29 were be VBD cord-014597-66vd2mdu 719 30 streamlined streamline VBN cord-014597-66vd2mdu 719 31 for for IN cord-014597-66vd2mdu 719 32 the the DT cord-014597-66vd2mdu 719 33 final final JJ cord-014597-66vd2mdu 719 34 medium medium NN cord-014597-66vd2mdu 719 35 : : : cord-014597-66vd2mdu 719 36 EXCELL EXCELL NNP cord-014597-66vd2mdu 719 37 ® ® NNP cord-014597-66vd2mdu 719 38 Advanced advanced JJ cord-014597-66vd2mdu 719 39 HD HD NNP cord-014597-66vd2mdu 719 40 Perfusion Perfusion NNP cord-014597-66vd2mdu 719 41 Medium Medium NNP cord-014597-66vd2mdu 719 42 . . . cord-014597-66vd2mdu 720 1 Using use VBG cord-014597-66vd2mdu 720 2 this this DT cord-014597-66vd2mdu 720 3 medium medium NN cord-014597-66vd2mdu 720 4 , , , cord-014597-66vd2mdu 720 5 a a DT cord-014597-66vd2mdu 720 6 CHO CHO NNP cord-014597-66vd2mdu 720 7 - - HYPH cord-014597-66vd2mdu 720 8 S S NNP cord-014597-66vd2mdu 720 9 and and CC cord-014597-66vd2mdu 720 10 a a DT cord-014597-66vd2mdu 720 11 CHOZN CHOZN NNP cord-014597-66vd2mdu 720 12 ® ® NN cord-014597-66vd2mdu 720 13 GS GS NNP cord-014597-66vd2mdu 720 14 cell cell NN cord-014597-66vd2mdu 720 15 line line NN cord-014597-66vd2mdu 720 16 producing produce VBG cord-014597-66vd2mdu 720 17 a a DT cord-014597-66vd2mdu 720 18 fusion fusion NN cord-014597-66vd2mdu 720 19 protein protein NN cord-014597-66vd2mdu 720 20 were be VBD cord-014597-66vd2mdu 720 21 cultured culture VBN cord-014597-66vd2mdu 720 22 at at IN cord-014597-66vd2mdu 720 23 a a DT cord-014597-66vd2mdu 720 24 CSPR CSPR NNP cord-014597-66vd2mdu 720 25 of of IN cord-014597-66vd2mdu 720 26 less less JJR cord-014597-66vd2mdu 720 27 than than IN cord-014597-66vd2mdu 720 28 40pL 40pl CD cord-014597-66vd2mdu 720 29 / / SYM cord-014597-66vd2mdu 720 30 cell cell NN cord-014597-66vd2mdu 720 31 / / SYM cord-014597-66vd2mdu 720 32 day day NN cord-014597-66vd2mdu 720 33 with with IN cord-014597-66vd2mdu 720 34 a a DT cord-014597-66vd2mdu 720 35 VCD vcd NN cord-014597-66vd2mdu 720 36 of of IN cord-014597-66vd2mdu 720 37 50 50 CD cord-014597-66vd2mdu 720 38 * * NFP cord-014597-66vd2mdu 720 39 10 10 CD cord-014597-66vd2mdu 720 40 6 6 CD cord-014597-66vd2mdu 720 41 vc vc NNP cord-014597-66vd2mdu 720 42 / / SYM cord-014597-66vd2mdu 720 43 mL. mL. NNP cord-014597-66vd2mdu 720 44 Metabolic metabolic JJ cord-014597-66vd2mdu 720 45 profile profile NN cord-014597-66vd2mdu 720 46 , , , cord-014597-66vd2mdu 720 47 productivity productivity NN cord-014597-66vd2mdu 720 48 , , , cord-014597-66vd2mdu 720 49 and and CC cord-014597-66vd2mdu 720 50 product product NN cord-014597-66vd2mdu 720 51 quality quality NN cord-014597-66vd2mdu 720 52 were be VBD cord-014597-66vd2mdu 720 53 constant constant JJ cord-014597-66vd2mdu 720 54 over over IN cord-014597-66vd2mdu 720 55 the the DT cord-014597-66vd2mdu 720 56 30 30 CD cord-014597-66vd2mdu 720 57 day day NN cord-014597-66vd2mdu 720 58 steady steady JJ cord-014597-66vd2mdu 720 59 state state NN cord-014597-66vd2mdu 720 60 . . . cord-014597-66vd2mdu 721 1 The the DT cord-014597-66vd2mdu 721 2 CHOZN CHOZN NNP cord-014597-66vd2mdu 721 3 ® ® NN cord-014597-66vd2mdu 721 4 GS GS NNP cord-014597-66vd2mdu 721 5 cell cell NN cord-014597-66vd2mdu 721 6 line line NN cord-014597-66vd2mdu 721 7 was be VBD cord-014597-66vd2mdu 721 8 also also RB cord-014597-66vd2mdu 721 9 tested test VBN cord-014597-66vd2mdu 721 10 at at IN cord-014597-66vd2mdu 721 11 80 80 CD cord-014597-66vd2mdu 721 12 * * SYM cord-014597-66vd2mdu 721 13 10 10 CD cord-014597-66vd2mdu 721 14 6 6 CD cord-014597-66vd2mdu 721 15 vc vc NN cord-014597-66vd2mdu 721 16 / / SYM cord-014597-66vd2mdu 721 17 mL ml NN cord-014597-66vd2mdu 721 18 with with IN cord-014597-66vd2mdu 721 19 a a DT cord-014597-66vd2mdu 721 20 CSPR CSPR NNP cord-014597-66vd2mdu 721 21 of of IN cord-014597-66vd2mdu 721 22 33pL 33pl CD cord-014597-66vd2mdu 721 23 / / SYM cord-014597-66vd2mdu 721 24 cell cell NN cord-014597-66vd2mdu 721 25 / / SYM cord-014597-66vd2mdu 721 26 day day NN cord-014597-66vd2mdu 722 1 ( ( -LRB- cord-014597-66vd2mdu 722 2 Fig Fig NNP cord-014597-66vd2mdu 722 3 . . NNP cord-014597-66vd2mdu 722 4 1 1 CD cord-014597-66vd2mdu 722 5 ) ) -RRB- cord-014597-66vd2mdu 722 6 . . . cord-014597-66vd2mdu 723 1 We -PRON- PRP cord-014597-66vd2mdu 723 2 have have VBP cord-014597-66vd2mdu 723 3 developed develop VBN cord-014597-66vd2mdu 723 4 a a DT cord-014597-66vd2mdu 723 5 catalog catalog NN cord-014597-66vd2mdu 723 6 perfusion perfusion NN cord-014597-66vd2mdu 723 7 medium medium NN cord-014597-66vd2mdu 723 8 from from IN cord-014597-66vd2mdu 723 9 first first JJ cord-014597-66vd2mdu 723 10 principles principle NNS cord-014597-66vd2mdu 723 11 , , , cord-014597-66vd2mdu 723 12 ensuring ensure VBG cord-014597-66vd2mdu 723 13 broadness broadness NN cord-014597-66vd2mdu 723 14 of of IN cord-014597-66vd2mdu 723 15 application application NN cord-014597-66vd2mdu 723 16 by by IN cord-014597-66vd2mdu 723 17 using use VBG cord-014597-66vd2mdu 723 18 seven seven CD cord-014597-66vd2mdu 723 19 cell cell NN cord-014597-66vd2mdu 723 20 lines line NNS cord-014597-66vd2mdu 723 21 in in IN cord-014597-66vd2mdu 723 22 scaleddown scaleddown NN cord-014597-66vd2mdu 723 23 systems system NNS cord-014597-66vd2mdu 723 24 and and CC cord-014597-66vd2mdu 723 25 four four CD cord-014597-66vd2mdu 723 26 in in IN cord-014597-66vd2mdu 723 27 perfusion perfusion NN cord-014597-66vd2mdu 723 28 bioreactors bioreactor NNS cord-014597-66vd2mdu 723 29 . . . cord-014597-66vd2mdu 724 1 The the DT cord-014597-66vd2mdu 724 2 final final JJ cord-014597-66vd2mdu 724 3 catalog catalog NN cord-014597-66vd2mdu 724 4 medium medium NN cord-014597-66vd2mdu 724 5 showed show VBD cord-014597-66vd2mdu 724 6 significant significant JJ cord-014597-66vd2mdu 724 7 improvements improvement NNS cord-014597-66vd2mdu 724 8 in in IN cord-014597-66vd2mdu 724 9 productivity productivity NN cord-014597-66vd2mdu 724 10 across across IN cord-014597-66vd2mdu 724 11 all all DT cord-014597-66vd2mdu 724 12 cell cell NN cord-014597-66vd2mdu 724 13 lines line NNS cord-014597-66vd2mdu 724 14 , , , cord-014597-66vd2mdu 724 15 with with IN cord-014597-66vd2mdu 724 16 reduced reduce VBN cord-014597-66vd2mdu 724 17 CSPRs cspr NNS cord-014597-66vd2mdu 724 18 when when WRB cord-014597-66vd2mdu 724 19 compared compare VBN cord-014597-66vd2mdu 724 20 to to IN cord-014597-66vd2mdu 724 21 enriched enrich VBN cord-014597-66vd2mdu 724 22 fed fed NNP cord-014597-66vd2mdu 724 23 - - HYPH cord-014597-66vd2mdu 724 24 batch batch NN cord-014597-66vd2mdu 724 25 medium medium NN cord-014597-66vd2mdu 724 26 or or CC cord-014597-66vd2mdu 724 27 initial initial JJ cord-014597-66vd2mdu 724 28 prototypes prototype NNS cord-014597-66vd2mdu 724 29 ( ( -LRB- cord-014597-66vd2mdu 724 30 Table table NN cord-014597-66vd2mdu 724 31 1 1 CD cord-014597-66vd2mdu 724 32 ) ) -RRB- cord-014597-66vd2mdu 724 33 . . . cord-014597-66vd2mdu 725 1 There there EX cord-014597-66vd2mdu 725 2 is be VBZ cord-014597-66vd2mdu 725 3 a a DT cord-014597-66vd2mdu 725 4 rising rise VBG cord-014597-66vd2mdu 725 5 demand demand NN cord-014597-66vd2mdu 725 6 for for IN cord-014597-66vd2mdu 725 7 accelerated accelerated JJ cord-014597-66vd2mdu 725 8 process process NN cord-014597-66vd2mdu 725 9 development development NN cord-014597-66vd2mdu 725 10 , , , cord-014597-66vd2mdu 725 11 increased increase VBN cord-014597-66vd2mdu 725 12 efficiency efficiency NN cord-014597-66vd2mdu 725 13 and and CC cord-014597-66vd2mdu 725 14 economics economic NNS cord-014597-66vd2mdu 725 15 for for IN cord-014597-66vd2mdu 725 16 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 725 17 production production NN cord-014597-66vd2mdu 725 18 processes process NNS cord-014597-66vd2mdu 725 19 . . . cord-014597-66vd2mdu 726 1 Furthermore furthermore RB cord-014597-66vd2mdu 726 2 , , , cord-014597-66vd2mdu 726 3 increased increase VBN cord-014597-66vd2mdu 726 4 process process NN cord-014597-66vd2mdu 726 5 understanding understanding NN cord-014597-66vd2mdu 726 6 have have VBP cord-014597-66vd2mdu 726 7 evolved evolve VBN cord-014597-66vd2mdu 726 8 from from IN cord-014597-66vd2mdu 726 9 the the DT cord-014597-66vd2mdu 726 10 Process Process NNP cord-014597-66vd2mdu 726 11 Analytical Analytical NNP cord-014597-66vd2mdu 726 12 Tool Tool NNP cord-014597-66vd2mdu 726 13 initiative initiative NN cord-014597-66vd2mdu 726 14 ( ( -LRB- cord-014597-66vd2mdu 726 15 PAT PAT NNP cord-014597-66vd2mdu 726 16 ) ) -RRB- cord-014597-66vd2mdu 726 17 and and CC cord-014597-66vd2mdu 726 18 the the DT cord-014597-66vd2mdu 726 19 Quality Quality NNP cord-014597-66vd2mdu 726 20 by by IN cord-014597-66vd2mdu 726 21 Design Design NNP cord-014597-66vd2mdu 726 22 ( ( -LRB- cord-014597-66vd2mdu 726 23 QbD qbd NN cord-014597-66vd2mdu 726 24 ) ) -RRB- cord-014597-66vd2mdu 726 25 methodology methodology NN cord-014597-66vd2mdu 726 26 . . . cord-014597-66vd2mdu 727 1 In in IN cord-014597-66vd2mdu 727 2 contrast contrast NN cord-014597-66vd2mdu 727 3 to to IN cord-014597-66vd2mdu 727 4 one one CD cord-014597-66vd2mdu 727 5 - - HYPH cord-014597-66vd2mdu 727 6 factor factor NN cord-014597-66vd2mdu 727 7 - - HYPH cord-014597-66vd2mdu 727 8 at at IN cord-014597-66vd2mdu 727 9 - - HYPH cord-014597-66vd2mdu 727 10 atime atime NN cord-014597-66vd2mdu 727 11 methods method NNS cord-014597-66vd2mdu 727 12 , , , cord-014597-66vd2mdu 727 13 statistical statistical JJ cord-014597-66vd2mdu 727 14 Design Design NNP cord-014597-66vd2mdu 727 15 of of IN cord-014597-66vd2mdu 727 16 Experiment Experiment NNP cord-014597-66vd2mdu 727 17 ( ( -LRB- cord-014597-66vd2mdu 727 18 DoE DoE NNP cord-014597-66vd2mdu 727 19 ) ) -RRB- cord-014597-66vd2mdu 727 20 methods method NNS cord-014597-66vd2mdu 727 21 are be VBP cord-014597-66vd2mdu 727 22 widely widely RB cord-014597-66vd2mdu 727 23 used use VBN cord-014597-66vd2mdu 727 24 to to TO cord-014597-66vd2mdu 727 25 develop develop VB cord-014597-66vd2mdu 727 26 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 727 27 processes process NNS cord-014597-66vd2mdu 727 28 . . . cord-014597-66vd2mdu 728 1 Even even RB cord-014597-66vd2mdu 728 2 if if IN cord-014597-66vd2mdu 728 3 highthroughput highthroughput NN cord-014597-66vd2mdu 728 4 systems system NNS cord-014597-66vd2mdu 728 5 can can MD cord-014597-66vd2mdu 728 6 handle handle VB cord-014597-66vd2mdu 728 7 these these DT cord-014597-66vd2mdu 728 8 numbers number NNS cord-014597-66vd2mdu 728 9 of of IN cord-014597-66vd2mdu 728 10 experiments experiment NNS cord-014597-66vd2mdu 728 11 in in IN cord-014597-66vd2mdu 728 12 parallel parallel NN cord-014597-66vd2mdu 728 13 , , , cord-014597-66vd2mdu 728 14 the the DT cord-014597-66vd2mdu 728 15 heuristic heuristic JJ cord-014597-66vd2mdu 728 16 restriction restriction NN cord-014597-66vd2mdu 728 17 of of IN cord-014597-66vd2mdu 728 18 boundaries boundary NNS cord-014597-66vd2mdu 728 19 and and CC cord-014597-66vd2mdu 728 20 the the DT cord-014597-66vd2mdu 728 21 high high JJ cord-014597-66vd2mdu 728 22 number number NN cord-014597-66vd2mdu 728 23 of of IN cord-014597-66vd2mdu 728 24 factors factor NNS cord-014597-66vd2mdu 728 25 results result NNS cord-014597-66vd2mdu 728 26 in in IN cord-014597-66vd2mdu 728 27 stepwise stepwise JJ cord-014597-66vd2mdu 728 28 iterations iteration NNS cord-014597-66vd2mdu 728 29 with with IN cord-014597-66vd2mdu 728 30 multiple multiple JJ cord-014597-66vd2mdu 728 31 runs run NNS cord-014597-66vd2mdu 728 32 . . . cord-014597-66vd2mdu 729 1 Therefore therefore RB cord-014597-66vd2mdu 729 2 , , , cord-014597-66vd2mdu 729 3 the the DT cord-014597-66vd2mdu 729 4 combination combination NN cord-014597-66vd2mdu 729 5 of of IN cord-014597-66vd2mdu 729 6 model model NN cord-014597-66vd2mdu 729 7 - - HYPH cord-014597-66vd2mdu 729 8 based base VBN cord-014597-66vd2mdu 729 9 simulations simulation NNS cord-014597-66vd2mdu 729 10 with with IN cord-014597-66vd2mdu 729 11 DoE DoE NNP cord-014597-66vd2mdu 729 12 methods method NNS cord-014597-66vd2mdu 729 13 ( ( -LRB- cord-014597-66vd2mdu 729 14 mDoE mdoe CD cord-014597-66vd2mdu 729 15 ) ) -RRB- cord-014597-66vd2mdu 729 16 for for IN cord-014597-66vd2mdu 729 17 the the DT cord-014597-66vd2mdu 729 18 development development NN cord-014597-66vd2mdu 729 19 of of IN cord-014597-66vd2mdu 729 20 sophisticated sophisticated JJ cord-014597-66vd2mdu 729 21 cell cell NN cord-014597-66vd2mdu 729 22 culture culture NN cord-014597-66vd2mdu 729 23 processes process NNS cord-014597-66vd2mdu 729 24 is be VBZ cord-014597-66vd2mdu 729 25 a a DT cord-014597-66vd2mdu 729 26 novel novel JJ cord-014597-66vd2mdu 729 27 tool tool NN cord-014597-66vd2mdu 729 28 for for IN cord-014597-66vd2mdu 729 29 process process NN cord-014597-66vd2mdu 729 30 development development NN cord-014597-66vd2mdu 729 31 [ [ -LRB- cord-014597-66vd2mdu 729 32 1 1 CD cord-014597-66vd2mdu 729 33 ] ] -RRB- cord-014597-66vd2mdu 729 34 . . . cord-014597-66vd2mdu 730 1 It -PRON- PRP cord-014597-66vd2mdu 730 2 is be VBZ cord-014597-66vd2mdu 730 3 used use VBN cord-014597-66vd2mdu 730 4 to to TO cord-014597-66vd2mdu 730 5 reduce reduce VB cord-014597-66vd2mdu 730 6 the the DT cord-014597-66vd2mdu 730 7 number number NN cord-014597-66vd2mdu 730 8 of of IN cord-014597-66vd2mdu 730 9 experiments experiment NNS cord-014597-66vd2mdu 730 10 during during IN cord-014597-66vd2mdu 730 11 DoE DoE NNP cord-014597-66vd2mdu 730 12 and and CC cord-014597-66vd2mdu 730 13 the the DT cord-014597-66vd2mdu 730 14 time time NN cord-014597-66vd2mdu 730 15 needed need VBN cord-014597-66vd2mdu 730 16 for for IN cord-014597-66vd2mdu 730 17 the the DT cord-014597-66vd2mdu 730 18 development development NN cord-014597-66vd2mdu 730 19 of of IN cord-014597-66vd2mdu 730 20 more more JJR cord-014597-66vd2mdu 730 21 knowledge knowledge NN cord-014597-66vd2mdu 730 22 - - HYPH cord-014597-66vd2mdu 730 23 based base VBN cord-014597-66vd2mdu 730 24 cell cell NN cord-014597-66vd2mdu 730 25 culture culture NN cord-014597-66vd2mdu 730 26 processes process NNS cord-014597-66vd2mdu 730 27 . . . cord-014597-66vd2mdu 731 1 This this DT cord-014597-66vd2mdu 731 2 concept concept NN cord-014597-66vd2mdu 731 3 was be VBD cord-014597-66vd2mdu 731 4 applied apply VBN cord-014597-66vd2mdu 731 5 to to IN cord-014597-66vd2mdu 731 6 the the DT cord-014597-66vd2mdu 731 7 optimization optimization NN cord-014597-66vd2mdu 731 8 of of IN cord-014597-66vd2mdu 731 9 the the DT cord-014597-66vd2mdu 731 10 initial initial JJ cord-014597-66vd2mdu 731 11 glutamine glutamine NN cord-014597-66vd2mdu 731 12 and and CC cord-014597-66vd2mdu 731 13 glucose glucose NN cord-014597-66vd2mdu 731 14 concentrations concentration NNS cord-014597-66vd2mdu 731 15 of of IN cord-014597-66vd2mdu 731 16 a a DT cord-014597-66vd2mdu 731 17 CHO CHO NNP cord-014597-66vd2mdu 731 18 batch batch NN cord-014597-66vd2mdu 731 19 process process NN cord-014597-66vd2mdu 731 20 . . . cord-014597-66vd2mdu 732 1 A a DT cord-014597-66vd2mdu 732 2 mechanistic mechanistic JJ cord-014597-66vd2mdu 732 3 model model NN cord-014597-66vd2mdu 732 4 was be VBD cord-014597-66vd2mdu 732 5 adapted adapt VBN cord-014597-66vd2mdu 732 6 and and CC cord-014597-66vd2mdu 732 7 modified modify VBN cord-014597-66vd2mdu 732 8 from from IN cord-014597-66vd2mdu 732 9 [ [ -LRB- cord-014597-66vd2mdu 732 10 2 2 CD cord-014597-66vd2mdu 732 11 ] ] -RRB- cord-014597-66vd2mdu 732 12 and and CC cord-014597-66vd2mdu 732 13 used use VBD cord-014597-66vd2mdu 732 14 to to TO cord-014597-66vd2mdu 732 15 describe describe VB cord-014597-66vd2mdu 732 16 the the DT cord-014597-66vd2mdu 732 17 dynamics dynamic NNS cord-014597-66vd2mdu 732 18 of of IN cord-014597-66vd2mdu 732 19 cell cell NN cord-014597-66vd2mdu 732 20 metabolism metabolism NN cord-014597-66vd2mdu 732 21 and and CC cord-014597-66vd2mdu 732 22 antibody antibody NN cord-014597-66vd2mdu 732 23 production production NN cord-014597-66vd2mdu 732 24 of of IN cord-014597-66vd2mdu 732 25 an an DT cord-014597-66vd2mdu 732 26 IL-8 IL-8 NNP cord-014597-66vd2mdu 732 27 antibody antibody NN cord-014597-66vd2mdu 732 28 producing produce VBG cord-014597-66vd2mdu 732 29 CHO CHO NNP cord-014597-66vd2mdu 732 30 cell cell NN cord-014597-66vd2mdu 732 31 line line NN cord-014597-66vd2mdu 732 32 ( ( -LRB- cord-014597-66vd2mdu 732 33 see see VB cord-014597-66vd2mdu 732 34 abbreviation abbreviation NN cord-014597-66vd2mdu 732 35 of of IN cord-014597-66vd2mdu 732 36 Fig Fig NNP cord-014597-66vd2mdu 732 37 . . . cord-014597-66vd2mdu 732 38 1 1 CD cord-014597-66vd2mdu 732 39 for for IN cord-014597-66vd2mdu 732 40 cultivation cultivation NN cord-014597-66vd2mdu 732 41 details detail NNS cord-014597-66vd2mdu 732 42 ) ) -RRB- cord-014597-66vd2mdu 732 43 . . . cord-014597-66vd2mdu 733 1 Experiments experiment NNS cord-014597-66vd2mdu 733 2 were be VBD cord-014597-66vd2mdu 733 3 simulated simulate VBN cord-014597-66vd2mdu 733 4 and and CC cord-014597-66vd2mdu 733 5 compared compare VBN cord-014597-66vd2mdu 733 6 to to IN cord-014597-66vd2mdu 733 7 a a DT cord-014597-66vd2mdu 733 8 fully fully RB cord-014597-66vd2mdu 733 9 experimental experimental JJ cord-014597-66vd2mdu 733 10 DoE. DoE. NNP cord-014597-66vd2mdu 733 11 As as IN cord-014597-66vd2mdu 733 12 can can MD cord-014597-66vd2mdu 733 13 be be VB cord-014597-66vd2mdu 733 14 seen see VBN cord-014597-66vd2mdu 733 15 from from IN cord-014597-66vd2mdu 733 16 Table table NN cord-014597-66vd2mdu 733 17 1 1 CD cord-014597-66vd2mdu 733 18 , , , cord-014597-66vd2mdu 733 19 user user NN cord-014597-66vd2mdu 733 20 defined define VBN cord-014597-66vd2mdu 733 21 constraints constraint NNS cord-014597-66vd2mdu 733 22 were be VBD cord-014597-66vd2mdu 733 23 chosen choose VBN cord-014597-66vd2mdu 733 24 to to TO cord-014597-66vd2mdu 733 25 get get VB cord-014597-66vd2mdu 733 26 a a DT cord-014597-66vd2mdu 733 27 stable stable JJ cord-014597-66vd2mdu 733 28 and and CC cord-014597-66vd2mdu 733 29 reproducible reproducible JJ cord-014597-66vd2mdu 733 30 process process NN cord-014597-66vd2mdu 733 31 with with IN cord-014597-66vd2mdu 733 32 the the DT cord-014597-66vd2mdu 733 33 aim aim NN cord-014597-66vd2mdu 733 34 of of IN cord-014597-66vd2mdu 733 35 maximizing maximize VBG cord-014597-66vd2mdu 733 36 the the DT cord-014597-66vd2mdu 733 37 cell cell NN cord-014597-66vd2mdu 733 38 density density NN cord-014597-66vd2mdu 733 39 but but CC cord-014597-66vd2mdu 733 40 decreased decrease VBD cord-014597-66vd2mdu 733 41 lactate lactate NN cord-014597-66vd2mdu 733 42 and and CC cord-014597-66vd2mdu 733 43 ammonia ammonia NN cord-014597-66vd2mdu 733 44 production production NN cord-014597-66vd2mdu 733 45 . . . cord-014597-66vd2mdu 734 1 At at IN cord-014597-66vd2mdu 734 2 first first RB cord-014597-66vd2mdu 734 3 , , , cord-014597-66vd2mdu 734 4 the the DT cord-014597-66vd2mdu 734 5 experimental experimental JJ cord-014597-66vd2mdu 734 6 space space NN cord-014597-66vd2mdu 734 7 was be VBD cord-014597-66vd2mdu 734 8 estimated estimate VBN cord-014597-66vd2mdu 734 9 by by IN cord-014597-66vd2mdu 734 10 simulating simulate VBG cord-014597-66vd2mdu 734 11 the the DT cord-014597-66vd2mdu 734 12 responses response NNS cord-014597-66vd2mdu 734 13 for for IN cord-014597-66vd2mdu 734 14 broad broad JJ cord-014597-66vd2mdu 734 15 concentration concentration NN cord-014597-66vd2mdu 734 16 ranges range NNS cord-014597-66vd2mdu 734 17 and and CC cord-014597-66vd2mdu 734 18 calculating calculate VBG cord-014597-66vd2mdu 734 19 the the DT cord-014597-66vd2mdu 734 20 multiple multiple JJ cord-014597-66vd2mdu 734 21 response response NN cord-014597-66vd2mdu 734 22 desirability desirability NN cord-014597-66vd2mdu 734 23 function function NN cord-014597-66vd2mdu 734 24 ( ( -LRB- cord-014597-66vd2mdu 734 25 Fig Fig NNP cord-014597-66vd2mdu 734 26 . . . cord-014597-66vd2mdu 734 27 1a 1a CD cord-014597-66vd2mdu 734 28 ) ) -RRB- cord-014597-66vd2mdu 734 29 . . . cord-014597-66vd2mdu 735 1 This this DT cord-014597-66vd2mdu 735 2 results result VBZ cord-014597-66vd2mdu 735 3 in in IN cord-014597-66vd2mdu 735 4 a a DT cord-014597-66vd2mdu 735 5 small small JJ cord-014597-66vd2mdu 735 6 area area NN cord-014597-66vd2mdu 735 7 ( ( -LRB- cord-014597-66vd2mdu 735 8 turquoise turquoise NN cord-014597-66vd2mdu 735 9 ) ) -RRB- cord-014597-66vd2mdu 735 10 suggested suggest VBD cord-014597-66vd2mdu 735 11 as as IN cord-014597-66vd2mdu 735 12 experimental experimental JJ cord-014597-66vd2mdu 735 13 space space NN cord-014597-66vd2mdu 735 14 . . . cord-014597-66vd2mdu 736 1 Experiments experiment NNS cord-014597-66vd2mdu 736 2 were be VBD cord-014597-66vd2mdu 736 3 planned plan VBN cord-014597-66vd2mdu 736 4 within within IN cord-014597-66vd2mdu 736 5 these these DT cord-014597-66vd2mdu 736 6 boundaries boundary NNS cord-014597-66vd2mdu 736 7 and and CC cord-014597-66vd2mdu 736 8 responses response NNS cord-014597-66vd2mdu 736 9 were be VBD cord-014597-66vd2mdu 736 10 either either RB cord-014597-66vd2mdu 736 11 simulated simulate VBN cord-014597-66vd2mdu 737 1 ( ( -LRB- cord-014597-66vd2mdu 737 2 Fig Fig NNP cord-014597-66vd2mdu 737 3 . . . cord-014597-66vd2mdu 737 4 1b 1b CD cord-014597-66vd2mdu 737 5 , , , cord-014597-66vd2mdu 737 6 4 4 CD cord-014597-66vd2mdu 737 7 cultivations cultivation NNS cord-014597-66vd2mdu 737 8 for for IN cord-014597-66vd2mdu 737 9 fitting fit VBG cord-014597-66vd2mdu 737 10 the the DT cord-014597-66vd2mdu 737 11 model model NN cord-014597-66vd2mdu 737 12 ) ) -RRB- cord-014597-66vd2mdu 737 13 or or CC cord-014597-66vd2mdu 738 1 compared compare VBN cord-014597-66vd2mdu 738 2 with with IN cord-014597-66vd2mdu 738 3 the the DT cord-014597-66vd2mdu 738 4 purely purely RB cord-014597-66vd2mdu 738 5 experimental experimental JJ cord-014597-66vd2mdu 738 6 responses response NNS cord-014597-66vd2mdu 738 7 ( ( -LRB- cord-014597-66vd2mdu 738 8 Fig Fig NNP cord-014597-66vd2mdu 738 9 . . . cord-014597-66vd2mdu 738 10 1c 1c NNP cord-014597-66vd2mdu 738 11 , , , cord-014597-66vd2mdu 738 12 16 16 CD cord-014597-66vd2mdu 738 13 cultivations cultivation NNS cord-014597-66vd2mdu 738 14 ) ) -RRB- cord-014597-66vd2mdu 738 15 . . . cord-014597-66vd2mdu 739 1 Optimal optimal JJ cord-014597-66vd2mdu 739 2 concentrations concentration NNS cord-014597-66vd2mdu 739 3 for for IN cord-014597-66vd2mdu 739 4 glutamine glutamine NN cord-014597-66vd2mdu 739 5 and and CC cord-014597-66vd2mdu 739 6 glucose glucose NN cord-014597-66vd2mdu 739 7 with with IN cord-014597-66vd2mdu 739 8 respect respect NN cord-014597-66vd2mdu 739 9 to to IN cord-014597-66vd2mdu 739 10 the the DT cord-014597-66vd2mdu 739 11 constraints constraint NNS cord-014597-66vd2mdu 739 12 are be VBP cord-014597-66vd2mdu 739 13 in in IN cord-014597-66vd2mdu 739 14 the the DT cord-014597-66vd2mdu 739 15 lower low JJR cord-014597-66vd2mdu 739 16 right right JJ cord-014597-66vd2mdu 739 17 corner corner NN cord-014597-66vd2mdu 739 18 and and CC cord-014597-66vd2mdu 739 19 similar similar JJ cord-014597-66vd2mdu 739 20 for for IN cord-014597-66vd2mdu 739 21 both both DT cord-014597-66vd2mdu 739 22 methods method NNS cord-014597-66vd2mdu 739 23 ( ( -LRB- cord-014597-66vd2mdu 739 24 red red JJ cord-014597-66vd2mdu 739 25 frame frame NN cord-014597-66vd2mdu 739 26 , , , cord-014597-66vd2mdu 739 27 Fig Fig NNP cord-014597-66vd2mdu 739 28 . . NNP cord-014597-66vd2mdu 739 29 1 1 CD cord-014597-66vd2mdu 739 30 ) ) -RRB- cord-014597-66vd2mdu 739 31 . . . cord-014597-66vd2mdu 740 1 Compared compare VBN cord-014597-66vd2mdu 740 2 with with IN cord-014597-66vd2mdu 740 3 the the DT cord-014597-66vd2mdu 740 4 fully fully RB cord-014597-66vd2mdu 740 5 experimental experimental JJ cord-014597-66vd2mdu 740 6 design design NN cord-014597-66vd2mdu 740 7 , , , cord-014597-66vd2mdu 740 8 mDoE mdoe NN cord-014597-66vd2mdu 740 9 results result NNS cord-014597-66vd2mdu 740 10 in in IN cord-014597-66vd2mdu 740 11 a a DT cord-014597-66vd2mdu 740 12 reduction reduction NN cord-014597-66vd2mdu 740 13 of of IN cord-014597-66vd2mdu 740 14 75 75 CD cord-014597-66vd2mdu 740 15 % % NN cord-014597-66vd2mdu 740 16 in in IN cord-014597-66vd2mdu 740 17 the the DT cord-014597-66vd2mdu 740 18 number number NN cord-014597-66vd2mdu 740 19 of of IN cord-014597-66vd2mdu 740 20 experiments experiment NNS cord-014597-66vd2mdu 740 21 ( ( -LRB- cord-014597-66vd2mdu 740 22 4 4 CD cord-014597-66vd2mdu 740 23 experiments experiment NNS cord-014597-66vd2mdu 740 24 for for IN cord-014597-66vd2mdu 740 25 modelling model VBG cord-014597-66vd2mdu 740 26 vs. vs. CC cord-014597-66vd2mdu 740 27 16 16 CD cord-014597-66vd2mdu 740 28 experiments experiment NNS cord-014597-66vd2mdu 740 29 in in IN cord-014597-66vd2mdu 740 30 experimental experimental JJ cord-014597-66vd2mdu 740 31 DoE doe NN cord-014597-66vd2mdu 740 32 ) ) -RRB- cord-014597-66vd2mdu 740 33 . . . cord-014597-66vd2mdu 741 1 The the DT cord-014597-66vd2mdu 741 2 method method NN cord-014597-66vd2mdu 741 3 is be VBZ cord-014597-66vd2mdu 741 4 intended intend VBN cord-014597-66vd2mdu 741 5 to to TO cord-014597-66vd2mdu 741 6 optimize optimize VB cord-014597-66vd2mdu 741 7 cultivation cultivation NN cord-014597-66vd2mdu 741 8 strategies strategy NNS cord-014597-66vd2mdu 741 9 for for IN cord-014597-66vd2mdu 741 10 mammalian mammalian JJ cord-014597-66vd2mdu 741 11 cell cell NN cord-014597-66vd2mdu 741 12 lines line NNS cord-014597-66vd2mdu 741 13 and and CC cord-014597-66vd2mdu 741 14 evaluated evaluate VBD cord-014597-66vd2mdu 741 15 these these DT cord-014597-66vd2mdu 741 16 before before IN cord-014597-66vd2mdu 741 17 experiments experiment NNS cord-014597-66vd2mdu 741 18 have have VBP cord-014597-66vd2mdu 741 19 to to TO cord-014597-66vd2mdu 741 20 be be VB cord-014597-66vd2mdu 741 21 performed perform VBN cord-014597-66vd2mdu 741 22 in in IN cord-014597-66vd2mdu 741 23 laboratory laboratory NN cord-014597-66vd2mdu 741 24 scale scale NN cord-014597-66vd2mdu 741 25 . . . cord-014597-66vd2mdu 742 1 This this DT cord-014597-66vd2mdu 742 2 results result VBZ cord-014597-66vd2mdu 742 3 in in IN cord-014597-66vd2mdu 742 4 a a DT cord-014597-66vd2mdu 742 5 significant significant JJ cord-014597-66vd2mdu 742 6 time time NN cord-014597-66vd2mdu 742 7 and and CC cord-014597-66vd2mdu 742 8 cost cost NN cord-014597-66vd2mdu 742 9 reduction reduction NN cord-014597-66vd2mdu 742 10 during during IN cord-014597-66vd2mdu 742 11 process process NN cord-014597-66vd2mdu 742 12 development development NN cord-014597-66vd2mdu 742 13 and and CC cord-014597-66vd2mdu 742 14 process process NN cord-014597-66vd2mdu 742 15 establishment establishment NN cord-014597-66vd2mdu 742 16 . . . cord-014597-66vd2mdu 743 1 The the DT cord-014597-66vd2mdu 743 2 strategy strategy NN cord-014597-66vd2mdu 743 3 is be VBZ cord-014597-66vd2mdu 743 4 especially especially RB cord-014597-66vd2mdu 743 5 intended intend VBN cord-014597-66vd2mdu 743 6 for for IN cord-014597-66vd2mdu 743 7 the the DT cord-014597-66vd2mdu 743 8 use use NN cord-014597-66vd2mdu 743 9 in in IN cord-014597-66vd2mdu 743 10 multi multi JJ cord-014597-66vd2mdu 743 11 - - JJ cord-014597-66vd2mdu 743 12 single single JJ cord-014597-66vd2mdu 743 13 - - HYPH cord-014597-66vd2mdu 743 14 use use NN cord-014597-66vd2mdu 743 15 - - HYPH cord-014597-66vd2mdu 743 16 devices device NNS cord-014597-66vd2mdu 743 17 to to TO cord-014597-66vd2mdu 743 18 speed speed VB cord-014597-66vd2mdu 743 19 up up RP cord-014597-66vd2mdu 743 20 process process NN cord-014597-66vd2mdu 743 21 development development NN cord-014597-66vd2mdu 743 22 . . . cord-014597-66vd2mdu 743 23 . . . cord-014597-66vd2mdu 744 1 At at IN cord-014597-66vd2mdu 744 2 a a DT cord-014597-66vd2mdu 744 3 target target NN cord-014597-66vd2mdu 744 4 cell cell NN cord-014597-66vd2mdu 744 5 density density NN cord-014597-66vd2mdu 744 6 of of IN cord-014597-66vd2mdu 744 7 50 50 CD cord-014597-66vd2mdu 744 8 * * NFP cord-014597-66vd2mdu 744 9 10 10 CD cord-014597-66vd2mdu 744 10 6 6 CD cord-014597-66vd2mdu 744 11 vc vc NNP cord-014597-66vd2mdu 744 12 / / SYM cord-014597-66vd2mdu 744 13 mL ml NN cord-014597-66vd2mdu 744 14 , , , cord-014597-66vd2mdu 744 15 volumetric volumetric JJ cord-014597-66vd2mdu 744 16 productivity productivity NN cord-014597-66vd2mdu 744 17 was be VBD cord-014597-66vd2mdu 744 18 stable stable JJ cord-014597-66vd2mdu 744 19 for for IN cord-014597-66vd2mdu 744 20 a a DT cord-014597-66vd2mdu 744 21 30 30 CD cord-014597-66vd2mdu 744 22 day day NN cord-014597-66vd2mdu 744 23 steady steady JJ cord-014597-66vd2mdu 744 24 state state NN cord-014597-66vd2mdu 744 25 with with IN cord-014597-66vd2mdu 744 26 EXCELL EXCELL NNP cord-014597-66vd2mdu 745 1 ® ® , cord-014597-66vd2mdu 745 2 Advanced advanced JJ cord-014597-66vd2mdu 745 3 HD HD NNP cord-014597-66vd2mdu 745 4 Perfusion Perfusion NNP cord-014597-66vd2mdu 745 5 Medium Medium NNP cord-014597-66vd2mdu 745 6 . . . cord-014597-66vd2mdu 746 1 Shorter short JJR cord-014597-66vd2mdu 746 2 steady steady JJ cord-014597-66vd2mdu 746 3 states state NNS cord-014597-66vd2mdu 746 4 were be VBD cord-014597-66vd2mdu 746 5 tested test VBN cord-014597-66vd2mdu 746 6 at at IN cord-014597-66vd2mdu 746 7 80 80 CD cord-014597-66vd2mdu 746 8 * * SYM cord-014597-66vd2mdu 746 9 10 10 CD cord-014597-66vd2mdu 746 10 6 6 CD cord-014597-66vd2mdu 746 11 vc vc NN cord-014597-66vd2mdu 746 12 / / SYM cord-014597-66vd2mdu 746 13 mL ml NN cord-014597-66vd2mdu 746 14 Background background NN cord-014597-66vd2mdu 746 15 For for IN cord-014597-66vd2mdu 746 16 the the DT cord-014597-66vd2mdu 746 17 large large JJ cord-014597-66vd2mdu 746 18 - - HYPH cord-014597-66vd2mdu 746 19 scale scale NN cord-014597-66vd2mdu 746 20 production production NN cord-014597-66vd2mdu 746 21 of of IN cord-014597-66vd2mdu 746 22 therapeutic therapeutic JJ cord-014597-66vd2mdu 746 23 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 746 24 , , , cord-014597-66vd2mdu 746 25 fedbatch fedbatch NN cord-014597-66vd2mdu 746 26 culture culture NN cord-014597-66vd2mdu 746 27 has have VBZ cord-014597-66vd2mdu 746 28 been be VBN cord-014597-66vd2mdu 746 29 widely widely RB cord-014597-66vd2mdu 746 30 used use VBN cord-014597-66vd2mdu 746 31 for for IN cord-014597-66vd2mdu 746 32 its -PRON- PRP$ cord-014597-66vd2mdu 746 33 operational operational JJ cord-014597-66vd2mdu 746 34 simplicity simplicity NN cord-014597-66vd2mdu 746 35 and and CC cord-014597-66vd2mdu 746 36 high high JJ cord-014597-66vd2mdu 746 37 titer titer NN cord-014597-66vd2mdu 746 38 . . . cord-014597-66vd2mdu 747 1 However however RB cord-014597-66vd2mdu 747 2 , , , cord-014597-66vd2mdu 747 3 repeated repeat VBN cord-014597-66vd2mdu 747 4 feeding feeding NN cord-014597-66vd2mdu 747 5 of of IN cord-014597-66vd2mdu 747 6 medium medium NN cord-014597-66vd2mdu 747 7 concentrates concentrate VBZ cord-014597-66vd2mdu 747 8 and/ and/ CD cord-014597-66vd2mdu 747 9 or or CC cord-014597-66vd2mdu 747 10 addition addition NN cord-014597-66vd2mdu 747 11 of of IN cord-014597-66vd2mdu 747 12 a a DT cord-014597-66vd2mdu 747 13 base base NN cord-014597-66vd2mdu 747 14 to to TO cord-014597-66vd2mdu 747 15 maintain maintain VB cord-014597-66vd2mdu 747 16 optimal optimal JJ cord-014597-66vd2mdu 748 1 pH pH NNP cord-014597-66vd2mdu 748 2 during during IN cord-014597-66vd2mdu 748 3 fed fed NNP cord-014597-66vd2mdu 748 4 - - HYPH cord-014597-66vd2mdu 748 5 batch batch NN cord-014597-66vd2mdu 748 6 culture culture NN cord-014597-66vd2mdu 748 7 lead lead VBP cord-014597-66vd2mdu 748 8 to to TO cord-014597-66vd2mdu 748 9 increase increase VB cord-014597-66vd2mdu 748 10 in in IN cord-014597-66vd2mdu 748 11 osmolality osmolality NN cord-014597-66vd2mdu 748 12 . . . cord-014597-66vd2mdu 749 1 The the DT cord-014597-66vd2mdu 749 2 hyperosmolality hyperosmolality NN cord-014597-66vd2mdu 749 3 affects affect VBZ cord-014597-66vd2mdu 749 4 glycosylation glycosylation NN cord-014597-66vd2mdu 749 5 in in IN cord-014597-66vd2mdu 749 6 a a DT cord-014597-66vd2mdu 749 7 protein protein NN cord-014597-66vd2mdu 749 8 - - HYPH cord-014597-66vd2mdu 749 9 specific specific JJ cord-014597-66vd2mdu 749 10 manner manner NN cord-014597-66vd2mdu 749 11 . . . cord-014597-66vd2mdu 750 1 However however RB cord-014597-66vd2mdu 750 2 , , , cord-014597-66vd2mdu 750 3 the the DT cord-014597-66vd2mdu 750 4 mechanism mechanism NN cord-014597-66vd2mdu 750 5 behind behind IN cord-014597-66vd2mdu 750 6 such such JJ cord-014597-66vd2mdu 750 7 osmolality osmolality NN cord-014597-66vd2mdu 750 8 - - HYPH cord-014597-66vd2mdu 750 9 dependent dependent JJ cord-014597-66vd2mdu 750 10 variations variation NNS cord-014597-66vd2mdu 750 11 in in IN cord-014597-66vd2mdu 750 12 glycosylation glycosylation NN cord-014597-66vd2mdu 750 13 in in IN cord-014597-66vd2mdu 750 14 recombinant recombinant JJ cord-014597-66vd2mdu 750 15 Chinese chinese JJ cord-014597-66vd2mdu 750 16 hamster hamster NN cord-014597-66vd2mdu 750 17 ovary ovary NN cord-014597-66vd2mdu 750 18 ( ( -LRB- cord-014597-66vd2mdu 750 19 rCHO rCHO NNP cord-014597-66vd2mdu 750 20 ) ) -RRB- cord-014597-66vd2mdu 750 21 cells cell NNS cord-014597-66vd2mdu 750 22 remains remain VBZ cord-014597-66vd2mdu 750 23 unclear unclear JJ cord-014597-66vd2mdu 750 24 . . . cord-014597-66vd2mdu 751 1 In in IN cord-014597-66vd2mdu 751 2 this this DT cord-014597-66vd2mdu 751 3 study study NN cord-014597-66vd2mdu 751 4 , , , cord-014597-66vd2mdu 751 5 to to TO cord-014597-66vd2mdu 751 6 better better RB cord-014597-66vd2mdu 751 7 understand understand VB cord-014597-66vd2mdu 751 8 the the DT cord-014597-66vd2mdu 751 9 effect effect NN cord-014597-66vd2mdu 751 10 of of IN cord-014597-66vd2mdu 751 11 hyperosmolality hyperosmolality NN cord-014597-66vd2mdu 751 12 on on IN cord-014597-66vd2mdu 751 13 the the DT cord-014597-66vd2mdu 751 14 glycosylation glycosylation NN cord-014597-66vd2mdu 751 15 of of IN cord-014597-66vd2mdu 751 16 a a DT cord-014597-66vd2mdu 751 17 protein protein NN cord-014597-66vd2mdu 751 18 produced produce VBN cord-014597-66vd2mdu 751 19 from from IN cord-014597-66vd2mdu 751 20 rCHO rcho JJ cord-014597-66vd2mdu 751 21 cells cell NNS cord-014597-66vd2mdu 751 22 , , , cord-014597-66vd2mdu 751 23 we -PRON- PRP cord-014597-66vd2mdu 751 24 investigated investigate VBD cord-014597-66vd2mdu 751 25 52 52 CD cord-014597-66vd2mdu 751 26 N n CD cord-014597-66vd2mdu 751 27 - - HYPH cord-014597-66vd2mdu 751 28 glycosylation glycosylation NN cord-014597-66vd2mdu 751 29 - - HYPH cord-014597-66vd2mdu 751 30 related relate VBN cord-014597-66vd2mdu 751 31 gene gene NN cord-014597-66vd2mdu 751 32 expression expression NN cord-014597-66vd2mdu 751 33 and and CC cord-014597-66vd2mdu 751 34 N n NN cord-014597-66vd2mdu 751 35 - - HYPH cord-014597-66vd2mdu 751 36 linked link VBN cord-014597-66vd2mdu 751 37 glycan glycan NN cord-014597-66vd2mdu 751 38 structure structure NN cord-014597-66vd2mdu 751 39 in in IN cord-014597-66vd2mdu 751 40 Fc Fc NNP cord-014597-66vd2mdu 751 41 - - HYPH cord-014597-66vd2mdu 751 42 fusion fusion NN cord-014597-66vd2mdu 751 43 protein protein NN cord-014597-66vd2mdu 751 44 - - HYPH cord-014597-66vd2mdu 751 45 producing produce VBG cord-014597-66vd2mdu 751 46 rCHO rcho NN cord-014597-66vd2mdu 751 47 cells cell NNS cord-014597-66vd2mdu 751 48 exposed expose VBN cord-014597-66vd2mdu 751 49 to to IN cord-014597-66vd2mdu 751 50 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 751 51 conditions condition NNS cord-014597-66vd2mdu 751 52 . . . cord-014597-66vd2mdu 752 1 Furthermore furthermore RB cord-014597-66vd2mdu 752 2 , , , cord-014597-66vd2mdu 752 3 to to TO cord-014597-66vd2mdu 752 4 validate validate VB cord-014597-66vd2mdu 752 5 the the DT cord-014597-66vd2mdu 752 6 effect effect NN cord-014597-66vd2mdu 752 7 of of IN cord-014597-66vd2mdu 752 8 hyperosmolality hyperosmolality NN cord-014597-66vd2mdu 752 9 on on IN cord-014597-66vd2mdu 752 10 protein protein NN cord-014597-66vd2mdu 752 11 glycosylation glycosylation NN cord-014597-66vd2mdu 752 12 , , , cord-014597-66vd2mdu 752 13 we -PRON- PRP cord-014597-66vd2mdu 752 14 performed perform VBD cord-014597-66vd2mdu 752 15 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 752 16 culture culture NN cord-014597-66vd2mdu 752 17 supplemented supplement VBN cord-014597-66vd2mdu 752 18 with with IN cord-014597-66vd2mdu 752 19 betaine betaine NN cord-014597-66vd2mdu 752 20 , , , cord-014597-66vd2mdu 752 21 an an DT cord-014597-66vd2mdu 752 22 osmoprotectant osmoprotectant NN cord-014597-66vd2mdu 752 23 , , , cord-014597-66vd2mdu 752 24 and and CC cord-014597-66vd2mdu 752 25 then then RB cord-014597-66vd2mdu 752 26 analyzed analyze VBD cord-014597-66vd2mdu 752 27 the the DT cord-014597-66vd2mdu 752 28 N N NNP cord-014597-66vd2mdu 752 29 - - HYPH cord-014597-66vd2mdu 752 30 linked link VBN cord-014597-66vd2mdu 752 31 glycan glycan NN cord-014597-66vd2mdu 752 32 structure structure NN cord-014597-66vd2mdu 752 33 and and CC cord-014597-66vd2mdu 752 34 mRNA mrna NN cord-014597-66vd2mdu 752 35 levels level NNS cord-014597-66vd2mdu 752 36 of of IN cord-014597-66vd2mdu 752 37 N n CD cord-014597-66vd2mdu 752 38 - - HYPH cord-014597-66vd2mdu 752 39 glycan glycan NN cord-014597-66vd2mdu 752 40 branching branch VBG cord-014597-66vd2mdu 752 41 / / SYM cord-014597-66vd2mdu 752 42 antennary antennary JJ cord-014597-66vd2mdu 752 43 genes gene NNS cord-014597-66vd2mdu 752 44 . . . cord-014597-66vd2mdu 753 1 After after IN cord-014597-66vd2mdu 753 2 three three CD cord-014597-66vd2mdu 753 3 days day NNS cord-014597-66vd2mdu 753 4 of of IN cord-014597-66vd2mdu 753 5 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 753 6 culture culture NN cord-014597-66vd2mdu 753 7 , , , cord-014597-66vd2mdu 753 8 nine nine CD cord-014597-66vd2mdu 753 9 genes gene NNS cord-014597-66vd2mdu 753 10 ( ( -LRB- cord-014597-66vd2mdu 753 11 ugp ugp JJ cord-014597-66vd2mdu 753 12 , , , cord-014597-66vd2mdu 753 13 slc35a3 slc35a3 NNP cord-014597-66vd2mdu 753 14 , , , cord-014597-66vd2mdu 753 15 slc35d2 slc35d2 NNP cord-014597-66vd2mdu 753 16 , , , cord-014597-66vd2mdu 753 17 gcs1 gcs1 UH cord-014597-66vd2mdu 753 18 , , , cord-014597-66vd2mdu 753 19 manea manea NNP cord-014597-66vd2mdu 753 20 , , , cord-014597-66vd2mdu 753 21 mgat2 mgat2 NN cord-014597-66vd2mdu 753 22 , , , cord-014597-66vd2mdu 753 23 mgat5b mgat5b NNP cord-014597-66vd2mdu 753 24 , , , cord-014597-66vd2mdu 753 25 b4galt3 b4galt3 JJ cord-014597-66vd2mdu 753 26 , , , cord-014597-66vd2mdu 753 27 and and CC cord-014597-66vd2mdu 753 28 b4galt4 b4galt4 LS cord-014597-66vd2mdu 753 29 ) ) -RRB- cord-014597-66vd2mdu 753 30 were be VBD cord-014597-66vd2mdu 753 31 differentially differentially RB cord-014597-66vd2mdu 753 32 expressed express VBN cord-014597-66vd2mdu 753 33 over over IN cord-014597-66vd2mdu 753 34 1.5-fold 1.5-fold CD cord-014597-66vd2mdu 753 35 of of IN cord-014597-66vd2mdu 753 36 the the DT cord-014597-66vd2mdu 753 37 control control NN cord-014597-66vd2mdu 753 38 , , , cord-014597-66vd2mdu 753 39 and and CC cord-014597-66vd2mdu 753 40 all all PDT cord-014597-66vd2mdu 753 41 these these DT cord-014597-66vd2mdu 753 42 genes gene NNS cord-014597-66vd2mdu 753 43 were be VBD cord-014597-66vd2mdu 753 44 down down RB cord-014597-66vd2mdu 753 45 - - HYPH cord-014597-66vd2mdu 753 46 regulated regulate VBN cord-014597-66vd2mdu 753 47 . . . cord-014597-66vd2mdu 754 1 N n CD cord-014597-66vd2mdu 754 2 - - HYPH cord-014597-66vd2mdu 754 3 linked link VBN cord-014597-66vd2mdu 754 4 glycan glycan NN cord-014597-66vd2mdu 754 5 analysis analysis NN cord-014597-66vd2mdu 754 6 by by IN cord-014597-66vd2mdu 754 7 anion anion NN cord-014597-66vd2mdu 754 8 exchange exchange NN cord-014597-66vd2mdu 754 9 and and CC cord-014597-66vd2mdu 754 10 hydrophilic hydrophilic JJ cord-014597-66vd2mdu 754 11 interaction interaction NN cord-014597-66vd2mdu 754 12 HPLC HPLC NNP cord-014597-66vd2mdu 754 13 showed show VBD cord-014597-66vd2mdu 754 14 that that IN cord-014597-66vd2mdu 754 15 the the DT cord-014597-66vd2mdu 754 16 proportion proportion NN cord-014597-66vd2mdu 754 17 of of IN cord-014597-66vd2mdu 754 18 highly highly RB cord-014597-66vd2mdu 754 19 sialylated sialylate VBN cord-014597-66vd2mdu 754 20 ( ( -LRB- cord-014597-66vd2mdu 754 21 di- di- XX cord-014597-66vd2mdu 754 22 , , , cord-014597-66vd2mdu 754 23 tri- tri- XX cord-014597-66vd2mdu 754 24 , , , cord-014597-66vd2mdu 754 25 tetra- tetra- NN cord-014597-66vd2mdu 754 26 ) ) -RRB- cord-014597-66vd2mdu 754 27 and and CC cord-014597-66vd2mdu 754 28 tetra tetra NNP cord-014597-66vd2mdu 754 29 - - HYPH cord-014597-66vd2mdu 754 30 antennary antennary NNP cord-014597-66vd2mdu 754 31 N N NNP cord-014597-66vd2mdu 754 32 - - HYPH cord-014597-66vd2mdu 754 33 linked link VBN cord-014597-66vd2mdu 754 34 glycans glycan NNS cord-014597-66vd2mdu 754 35 was be VBD cord-014597-66vd2mdu 754 36 significantly significantly RB cord-014597-66vd2mdu 754 37 decreased decrease VBN cord-014597-66vd2mdu 754 38 upon upon IN cord-014597-66vd2mdu 754 39 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 754 40 culture culture NN cord-014597-66vd2mdu 754 41 . . . cord-014597-66vd2mdu 755 1 Addition addition NN cord-014597-66vd2mdu 755 2 of of IN cord-014597-66vd2mdu 755 3 betaine betaine NN cord-014597-66vd2mdu 755 4 , , , cord-014597-66vd2mdu 755 5 an an DT cord-014597-66vd2mdu 755 6 osmoprotectant osmoprotectant NN cord-014597-66vd2mdu 755 7 , , , cord-014597-66vd2mdu 755 8 to to IN cord-014597-66vd2mdu 755 9 the the DT cord-014597-66vd2mdu 755 10 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 755 11 culture culture NN cord-014597-66vd2mdu 755 12 significantly significantly RB cord-014597-66vd2mdu 755 13 increased increase VBD cord-014597-66vd2mdu 755 14 the the DT cord-014597-66vd2mdu 755 15 proportion proportion NN cord-014597-66vd2mdu 755 16 of of IN cord-014597-66vd2mdu 755 17 highly highly RB cord-014597-66vd2mdu 755 18 sialylated sialylate VBN cord-014597-66vd2mdu 755 19 and and CC cord-014597-66vd2mdu 755 20 tetra tetra NNP cord-014597-66vd2mdu 755 21 - - HYPH cord-014597-66vd2mdu 755 22 antennary antennary NNP cord-014597-66vd2mdu 755 23 N N NNP cord-014597-66vd2mdu 755 24 - - HYPH cord-014597-66vd2mdu 755 25 linked link VBN cord-014597-66vd2mdu 755 26 glycans glycan NNS cord-014597-66vd2mdu 755 27 ( ( -LRB- cord-014597-66vd2mdu 755 28 P p NN cord-014597-66vd2mdu 755 29 ≤ ≤ NN cord-014597-66vd2mdu 755 30 0.05 0.05 CD cord-014597-66vd2mdu 755 31 ) ) -RRB- cord-014597-66vd2mdu 755 32 , , , cord-014597-66vd2mdu 755 33 while while IN cord-014597-66vd2mdu 755 34 it -PRON- PRP cord-014597-66vd2mdu 755 35 increased increase VBD cord-014597-66vd2mdu 755 36 the the DT cord-014597-66vd2mdu 755 37 expression expression NN cord-014597-66vd2mdu 755 38 of of IN cord-014597-66vd2mdu 755 39 the the DT cord-014597-66vd2mdu 755 40 N n CD cord-014597-66vd2mdu 755 41 - - HYPH cord-014597-66vd2mdu 755 42 glycan glycan NN cord-014597-66vd2mdu 755 43 branching branch VBG cord-014597-66vd2mdu 755 44 / / SYM cord-014597-66vd2mdu 755 45 antennary antennary JJ cord-014597-66vd2mdu 755 46 genes gene NNS cord-014597-66vd2mdu 755 47 ( ( -LRB- cord-014597-66vd2mdu 755 48 mgat2 mgat2 NNP cord-014597-66vd2mdu 755 49 and and CC cord-014597-66vd2mdu 755 50 mgat4b mgat4b NNP cord-014597-66vd2mdu 755 51 ) ) -RRB- cord-014597-66vd2mdu 755 52 . . . cord-014597-66vd2mdu 756 1 Thus thus RB cord-014597-66vd2mdu 756 2 , , , cord-014597-66vd2mdu 756 3 decreased decrease VBD cord-014597-66vd2mdu 756 4 expression expression NN cord-014597-66vd2mdu 756 5 of of IN cord-014597-66vd2mdu 756 6 the the DT cord-014597-66vd2mdu 756 7 genes gene NNS cord-014597-66vd2mdu 756 8 with with IN cord-014597-66vd2mdu 756 9 roles role NNS cord-014597-66vd2mdu 756 10 in in IN cord-014597-66vd2mdu 756 11 the the DT cord-014597-66vd2mdu 756 12 N n CD cord-014597-66vd2mdu 756 13 - - HYPH cord-014597-66vd2mdu 756 14 glycan glycan NN cord-014597-66vd2mdu 756 15 biosynthesis biosynthesis NN cord-014597-66vd2mdu 756 16 pathway pathway NN cord-014597-66vd2mdu 756 17 correlated correlate VBN cord-014597-66vd2mdu 756 18 with with IN cord-014597-66vd2mdu 756 19 reduced reduce VBN cord-014597-66vd2mdu 756 20 sialic sialic NN cord-014597-66vd2mdu 756 21 acid acid NN cord-014597-66vd2mdu 756 22 content content NN cord-014597-66vd2mdu 756 23 of of IN cord-014597-66vd2mdu 756 24 Fc Fc NNP cord-014597-66vd2mdu 756 25 - - HYPH cord-014597-66vd2mdu 756 26 fusion fusion NN cord-014597-66vd2mdu 756 27 protein protein NN cord-014597-66vd2mdu 756 28 caused cause VBN cord-014597-66vd2mdu 756 29 by by IN cord-014597-66vd2mdu 756 30 hyperosmolar hyperosmolar JJ cord-014597-66vd2mdu 756 31 conditions condition NNS cord-014597-66vd2mdu 756 32 . . . cord-014597-66vd2mdu 757 1 Conclusions conclusion NNS cord-014597-66vd2mdu 757 2 Taken take VBN cord-014597-66vd2mdu 757 3 together together RB cord-014597-66vd2mdu 757 4 , , , cord-014597-66vd2mdu 757 5 the the DT cord-014597-66vd2mdu 757 6 results result NNS cord-014597-66vd2mdu 757 7 obtained obtain VBN cord-014597-66vd2mdu 757 8 in in IN cord-014597-66vd2mdu 757 9 this this DT cord-014597-66vd2mdu 757 10 study study NN cord-014597-66vd2mdu 757 11 provide provide VB cord-014597-66vd2mdu 757 12 a a DT cord-014597-66vd2mdu 757 13 better well JJR cord-014597-66vd2mdu 757 14 understanding understanding NN cord-014597-66vd2mdu 757 15 of of IN cord-014597-66vd2mdu 757 16 the the DT cord-014597-66vd2mdu 757 17 detrimental detrimental JJ cord-014597-66vd2mdu 757 18 effects effect NNS cord-014597-66vd2mdu 757 19 of of IN cord-014597-66vd2mdu 757 20 hyperosmolality hyperosmolality NN cord-014597-66vd2mdu 757 21 on on IN cord-014597-66vd2mdu 757 22 N n NN cord-014597-66vd2mdu 757 23 - - HYPH cord-014597-66vd2mdu 757 24 glycosylation glycosylation NN cord-014597-66vd2mdu 757 25 , , , cord-014597-66vd2mdu 757 26 especially especially RB cord-014597-66vd2mdu 757 27 sialylation sialylation NN cord-014597-66vd2mdu 757 28 , , , cord-014597-66vd2mdu 757 29 in in IN cord-014597-66vd2mdu 757 30 rCHO rcho NN cord-014597-66vd2mdu 757 31 cells cell NNS cord-014597-66vd2mdu 757 32 . . . cord-014597-66vd2mdu 758 1 The the DT cord-014597-66vd2mdu 758 2 identified identify VBN cord-014597-66vd2mdu 758 3 genes gene NNS cord-014597-66vd2mdu 758 4 , , , cord-014597-66vd2mdu 758 5 particularly particularly RB cord-014597-66vd2mdu 758 6 mgat2 mgat2 NN cord-014597-66vd2mdu 758 7 and and CC cord-014597-66vd2mdu 758 8 mgat4b mgat4b NNP cord-014597-66vd2mdu 758 9 , , , cord-014597-66vd2mdu 758 10 are be VBP cord-014597-66vd2mdu 758 11 potential potential JJ cord-014597-66vd2mdu 758 12 targets target NNS cord-014597-66vd2mdu 758 13 for for IN cord-014597-66vd2mdu 758 14 engineering engineering NN cord-014597-66vd2mdu 758 15 in in IN cord-014597-66vd2mdu 758 16 CHO CHO NNP cord-014597-66vd2mdu 758 17 cells cell NNS cord-014597-66vd2mdu 758 18 to to TO cord-014597-66vd2mdu 758 19 overcome overcome VB cord-014597-66vd2mdu 758 20 the the DT cord-014597-66vd2mdu 758 21 impact impact NN cord-014597-66vd2mdu 758 22 of of IN cord-014597-66vd2mdu 758 23 hyperosmolality hyperosmolality NN cord-014597-66vd2mdu 758 24 on on IN cord-014597-66vd2mdu 758 25 glycoprotein glycoprotein NN cord-014597-66vd2mdu 758 26 sialylation sialylation NN cord-014597-66vd2mdu 758 27 . . . cord-014597-66vd2mdu 759 1 Disruptive disruptive JJ cord-014597-66vd2mdu 759 2 cost cost NN cord-014597-66vd2mdu 759 3 - - HYPH cord-014597-66vd2mdu 759 4 effective effective JJ cord-014597-66vd2mdu 759 5 antibody antibody NN cord-014597-66vd2mdu 759 6 manufacturing manufacturing NN cord-014597-66vd2mdu 759 7 platform platform NN cord-014597-66vd2mdu 759 8 based base VBN cord-014597-66vd2mdu 759 9 on on IN cord-014597-66vd2mdu 759 10 cutting cut VBG cord-014597-66vd2mdu 759 11 - - HYPH cord-014597-66vd2mdu 759 12 edge edge NN cord-014597-66vd2mdu 759 13 purification purification NN cord-014597-66vd2mdu 759 14 process process NN cord-014597-66vd2mdu 759 15 V. V. NNP cord-014597-66vd2mdu 759 16 Medvedev Medvedev NNP cord-014597-66vd2mdu 759 17 , , , cord-014597-66vd2mdu 759 18 M. M. NNP cord-014597-66vd2mdu 759 19 Duyck Duyck NNP cord-014597-66vd2mdu 759 20 , , , cord-014597-66vd2mdu 759 21 T. T. NNP cord-014597-66vd2mdu 759 22 Albano Albano NNP cord-014597-66vd2mdu 759 23 , , , cord-014597-66vd2mdu 759 24 J. J. NNP cord-014597-66vd2mdu 759 25 Castillo Castillo NNP cord-014597-66vd2mdu 759 26 Univercells Univercells NNP cord-014597-66vd2mdu 759 27 SA SA NNP cord-014597-66vd2mdu 759 28 , , , cord-014597-66vd2mdu 759 29 Gosselies Gosselies NNP cord-014597-66vd2mdu 759 30 , , , cord-014597-66vd2mdu 759 31 Belgium Belgium NNP cord-014597-66vd2mdu 759 32 Correspondence Correspondence NNP cord-014597-66vd2mdu 759 33 : : : cord-014597-66vd2mdu 759 34 V. V. NNP cord-014597-66vd2mdu 759 35 Medvedev Medvedev NNP cord-014597-66vd2mdu 759 36 ( ( -LRB- cord-014597-66vd2mdu 759 37 v.medvedev@univercells.com v.medvedev@univercells.com ADD cord-014597-66vd2mdu 759 38 ) ) -RRB- cord-014597-66vd2mdu 760 1 BMC BMC NNP cord-014597-66vd2mdu 760 2 Proceedings Proceedings NNP cord-014597-66vd2mdu 760 3 2018 2018 CD cord-014597-66vd2mdu 760 4 , , , cord-014597-66vd2mdu 761 1 12(Suppl 12(suppl CD cord-014597-66vd2mdu 762 1 1):P-093 1):p-093 CD cord-014597-66vd2mdu 763 1 Background background NN cord-014597-66vd2mdu 763 2 Demand demand NN cord-014597-66vd2mdu 763 3 for for IN cord-014597-66vd2mdu 763 4 high high JJ cord-014597-66vd2mdu 763 5 - - HYPH cord-014597-66vd2mdu 763 6 quality quality NN cord-014597-66vd2mdu 763 7 monoclonal monoclonal JJ cord-014597-66vd2mdu 763 8 antibodies antibody NNS cord-014597-66vd2mdu 763 9 is be VBZ cord-014597-66vd2mdu 763 10 growing grow VBG cord-014597-66vd2mdu 763 11 exponentially exponentially RB cord-014597-66vd2mdu 763 12 , , , cord-014597-66vd2mdu 763 13 calling call VBG cord-014597-66vd2mdu 763 14 for for IN cord-014597-66vd2mdu 763 15 new new JJ cord-014597-66vd2mdu 763 16 production production NN cord-014597-66vd2mdu 763 17 capacities capacity NNS cord-014597-66vd2mdu 763 18 . . . cord-014597-66vd2mdu 764 1 Overcoming overcome VBG cord-014597-66vd2mdu 764 2 current current JJ cord-014597-66vd2mdu 764 3 limitations limitation NNS cord-014597-66vd2mdu 764 4 of of IN cord-014597-66vd2mdu 764 5 conventional conventional JJ cord-014597-66vd2mdu 764 6 manufacturing manufacturing NN cord-014597-66vd2mdu 764 7 strategies strategy NNS cord-014597-66vd2mdu 764 8 , , , cord-014597-66vd2mdu 764 9 namely namely RB cord-014597-66vd2mdu 764 10 the the DT cord-014597-66vd2mdu 764 11 high high JJ cord-014597-66vd2mdu 764 12 capital capital NN cord-014597-66vd2mdu 764 13 investment investment NN cord-014597-66vd2mdu 764 14 and and CC cord-014597-66vd2mdu 764 15 production production NN cord-014597-66vd2mdu 764 16 cost cost NN cord-014597-66vd2mdu 764 17 , , , cord-014597-66vd2mdu 764 18 can can MD cord-014597-66vd2mdu 764 19 only only RB cord-014597-66vd2mdu 764 20 be be VB cord-014597-66vd2mdu 764 21 achieved achieve VBN cord-014597-66vd2mdu 764 22 through through IN cord-014597-66vd2mdu 764 23 innovative innovative JJ cord-014597-66vd2mdu 764 24 process process NN cord-014597-66vd2mdu 764 25 designs design NNS cord-014597-66vd2mdu 764 26 based base VBN cord-014597-66vd2mdu 764 27 on on IN cord-014597-66vd2mdu 764 28 the the DT cord-014597-66vd2mdu 764 29 latest late JJS cord-014597-66vd2mdu 764 30 technologies technology NNS cord-014597-66vd2mdu 764 31 . . . cord-014597-66vd2mdu 765 1 This this DT cord-014597-66vd2mdu 765 2 study study NN cord-014597-66vd2mdu 765 3 presents present VBZ cord-014597-66vd2mdu 765 4 a a DT cord-014597-66vd2mdu 765 5 process process NN cord-014597-66vd2mdu 765 6 design design NN cord-014597-66vd2mdu 765 7 combining combine VBG cord-014597-66vd2mdu 765 8 batch batch NN cord-014597-66vd2mdu 765 9 - - HYPH cord-014597-66vd2mdu 765 10 fed fed JJ cord-014597-66vd2mdu 765 11 technology technology NN cord-014597-66vd2mdu 765 12 with with IN cord-014597-66vd2mdu 765 13 continuous continuous JJ cord-014597-66vd2mdu 765 14 multi multi JJ cord-014597-66vd2mdu 765 15 - - JJ cord-014597-66vd2mdu 765 16 column column JJ cord-014597-66vd2mdu 765 17 capture capture NN cord-014597-66vd2mdu 765 18 . . . cord-014597-66vd2mdu 766 1 An an DT cord-014597-66vd2mdu 766 2 advanced advanced JJ cord-014597-66vd2mdu 766 3 cell cell NN cord-014597-66vd2mdu 766 4 culture culture NN cord-014597-66vd2mdu 766 5 clarification clarification NN cord-014597-66vd2mdu 766 6 method method NN cord-014597-66vd2mdu 766 7 was be VBD cord-014597-66vd2mdu 766 8 introduced introduce VBN cord-014597-66vd2mdu 766 9 to to TO cord-014597-66vd2mdu 766 10 simplify simplify VB cord-014597-66vd2mdu 766 11 downstream downstream JJ cord-014597-66vd2mdu 766 12 operations operation NNS cord-014597-66vd2mdu 766 13 and and CC cord-014597-66vd2mdu 766 14 increase increase VB cord-014597-66vd2mdu 766 15 overall overall JJ cord-014597-66vd2mdu 766 16 cost cost NN cord-014597-66vd2mdu 766 17 - - HYPH cord-014597-66vd2mdu 766 18 effectiveness effectiveness NN cord-014597-66vd2mdu 766 19 of of IN cord-014597-66vd2mdu 766 20 the the DT cord-014597-66vd2mdu 766 21 process process NN cord-014597-66vd2mdu 766 22 , , , cord-014597-66vd2mdu 766 23 for for IN cord-014597-66vd2mdu 766 24 an an DT cord-014597-66vd2mdu 766 25 optimized optimize VBN cord-014597-66vd2mdu 766 26 production production NN cord-014597-66vd2mdu 766 27 of of IN cord-014597-66vd2mdu 766 28 recombinant recombinant JJ cord-014597-66vd2mdu 766 29 proteins protein NNS cord-014597-66vd2mdu 766 30 . . . cord-014597-66vd2mdu 767 1 This this DT cord-014597-66vd2mdu 767 2 study study NN cord-014597-66vd2mdu 767 3 was be VBD cord-014597-66vd2mdu 767 4 performed perform VBN cord-014597-66vd2mdu 767 5 with with IN cord-014597-66vd2mdu 767 6 CHO CHO NNP cord-014597-66vd2mdu 767 7 cells cell NNS cord-014597-66vd2mdu 767 8 expressing express VBG cord-014597-66vd2mdu 767 9 a a DT cord-014597-66vd2mdu 767 10 monoclonal monoclonal JJ cord-014597-66vd2mdu 767 11 antibody antibody NN cord-014597-66vd2mdu 767 12 targeted target VBN cord-014597-66vd2mdu 767 13 against against IN cord-014597-66vd2mdu 767 14 the the DT cord-014597-66vd2mdu 767 15 Coronoavirus Coronoavirus NNP cord-014597-66vd2mdu 767 16 responsible responsible JJ cord-014597-66vd2mdu 767 17 for for IN cord-014597-66vd2mdu 767 18 the the DT cord-014597-66vd2mdu 767 19 Middle Middle NNP cord-014597-66vd2mdu 767 20 East East NNP cord-014597-66vd2mdu 767 21 Respiratory Respiratory NNP cord-014597-66vd2mdu 767 22 Syndrome Syndrome NNP cord-014597-66vd2mdu 767 23 ( ( -LRB- cord-014597-66vd2mdu 767 24 MERS MERS NNP cord-014597-66vd2mdu 767 25 ) ) -RRB- cord-014597-66vd2mdu 767 26 , , , cord-014597-66vd2mdu 767 27 developed develop VBN cord-014597-66vd2mdu 767 28 by by IN cord-014597-66vd2mdu 767 29 Organic Organic NNP cord-014597-66vd2mdu 767 30 Vaccines Vaccines NNPS cord-014597-66vd2mdu 767 31 TM TM NNP cord-014597-66vd2mdu 767 32 and and CC cord-014597-66vd2mdu 767 33 the the DT cord-014597-66vd2mdu 767 34 NIH NIH NNP cord-014597-66vd2mdu 767 35 , , , cord-014597-66vd2mdu 767 36 kindly kindly RB cord-014597-66vd2mdu 767 37 provided provide VBD cord-014597-66vd2mdu 767 38 to to IN cord-014597-66vd2mdu 767 39 Univercells Univercells NNP cord-014597-66vd2mdu 767 40 . . . cord-014597-66vd2mdu 768 1 Upstream upstream JJ cord-014597-66vd2mdu 768 2 process process NN cord-014597-66vd2mdu 768 3 : : : cord-014597-66vd2mdu 768 4 -Fed -Fed NFP cord-014597-66vd2mdu 768 5 - - HYPH cord-014597-66vd2mdu 768 6 batch batch NN cord-014597-66vd2mdu 768 7 , , , cord-014597-66vd2mdu 768 8 12 12 CD cord-014597-66vd2mdu 768 9 days day NNS cord-014597-66vd2mdu 768 10 culture culture NN cord-014597-66vd2mdu 768 11 at at IN cord-014597-66vd2mdu 768 12 10L 10l JJ cord-014597-66vd2mdu 768 13 scale scale NN cord-014597-66vd2mdu 768 14 with with IN cord-014597-66vd2mdu 768 15 CD CD NNP cord-014597-66vd2mdu 768 16 - - HYPH cord-014597-66vd2mdu 768 17 CHO CHO NNP cord-014597-66vd2mdu 768 18 chemically chemically RB cord-014597-66vd2mdu 768 19 defined define VBD cord-014597-66vd2mdu 768 20 media medium NNS cord-014597-66vd2mdu 768 21 and and CC cord-014597-66vd2mdu 768 22 feeds feed NNS cord-014597-66vd2mdu 768 23 . . . cord-014597-66vd2mdu 769 1 Harvest harvest NN cord-014597-66vd2mdu 769 2 treatment treatment NN cord-014597-66vd2mdu 769 3 : : : cord-014597-66vd2mdu 770 1 -Precipitation -precipitation NN cord-014597-66vd2mdu 770 2 of of IN cord-014597-66vd2mdu 770 3 impurities impurity NNS cord-014597-66vd2mdu 770 4 in in IN cord-014597-66vd2mdu 770 5 the the DT cord-014597-66vd2mdu 770 6 production production NN cord-014597-66vd2mdu 770 7 bioreactor bioreactor NN cord-014597-66vd2mdu 770 8 using use VBG cord-014597-66vd2mdu 770 9 organic organic JJ cord-014597-66vd2mdu 770 10 compounds compound NNS cord-014597-66vd2mdu 770 11 ( ( -LRB- cord-014597-66vd2mdu 770 12 < < NNP cord-014597-66vd2mdu 770 13 1 1 CD cord-014597-66vd2mdu 770 14 % % NN cord-014597-66vd2mdu 770 15 v v NN cord-014597-66vd2mdu 770 16 / / SYM cord-014597-66vd2mdu 770 17 v v NN cord-014597-66vd2mdu 770 18 ) ) -RRB- cord-014597-66vd2mdu 770 19 and and CC cord-014597-66vd2mdu 770 20 flocculation flocculation NN cord-014597-66vd2mdu 770 21 by by IN cord-014597-66vd2mdu 770 22 electropositive electropositive JJ cord-014597-66vd2mdu 770 23 organics organic NNS cord-014597-66vd2mdu 770 24 ( ( -LRB- cord-014597-66vd2mdu 770 25 < < XX cord-014597-66vd2mdu 770 26 0.1 0.1 CD cord-014597-66vd2mdu 770 27 % % NN cord-014597-66vd2mdu 770 28 w w NN cord-014597-66vd2mdu 770 29 / / SYM cord-014597-66vd2mdu 770 30 v v NN cord-014597-66vd2mdu 770 31 ) ) -RRB- cord-014597-66vd2mdu 770 32 . . . cord-014597-66vd2mdu 771 1 -Acidic -Acidic NNP cord-014597-66vd2mdu 772 1 pH pH NNP cord-014597-66vd2mdu 772 2 and and CC cord-014597-66vd2mdu 772 3 physiological physiological JJ cord-014597-66vd2mdu 772 4 conductivity conductivity NN cord-014597-66vd2mdu 772 5 . . . cord-014597-66vd2mdu 772 6 _SP cord-014597-66vd2mdu 773 1 Upstream upstream JJ cord-014597-66vd2mdu 773 2 processing processing NN cord-014597-66vd2mdu 773 3 and and CC cord-014597-66vd2mdu 773 4 harvest harvest NN cord-014597-66vd2mdu 773 5 treatment treatment NN cord-014597-66vd2mdu 773 6 : : : cord-014597-66vd2mdu 773 7 Culture culture NN cord-014597-66vd2mdu 773 8 reached reach VBD cord-014597-66vd2mdu 773 9 0.5 0.5 CD cord-014597-66vd2mdu 773 10 g/ g/ NN cord-014597-66vd2mdu 773 11 L l NN cord-014597-66vd2mdu 773 12 ( ( -LRB- cord-014597-66vd2mdu 773 13 8x10 8x10 CD cord-014597-66vd2mdu 773 14 6 6 CD cord-014597-66vd2mdu 773 15 cells cell NNS cord-014597-66vd2mdu 773 16 / / SYM cord-014597-66vd2mdu 773 17 mL ml NN cord-014597-66vd2mdu 773 18 ; ; : cord-014597-66vd2mdu 773 19 90 90 CD cord-014597-66vd2mdu 773 20 % % NN cord-014597-66vd2mdu 773 21 viability viability NN cord-014597-66vd2mdu 773 22 ) ) -RRB- cord-014597-66vd2mdu 773 23 , , , cord-014597-66vd2mdu 773 24 harvest harvest NN cord-014597-66vd2mdu 773 25 treatment treatment NN cord-014597-66vd2mdu 773 26 was be VBD cord-014597-66vd2mdu 773 27 found find VBN cord-014597-66vd2mdu 773 28 to to TO cord-014597-66vd2mdu 773 29 be be VB cord-014597-66vd2mdu 773 30 very very RB cord-014597-66vd2mdu 773 31 effective effective JJ cord-014597-66vd2mdu 773 32 in in IN cord-014597-66vd2mdu 773 33 terms term NNS cord-014597-66vd2mdu 773 34 of of IN cord-014597-66vd2mdu 773 35 impurities impurity NNS cord-014597-66vd2mdu 773 36 clearance clearance NN cord-014597-66vd2mdu 773 37 . . . cord-014597-66vd2mdu 774 1 Capture capture VB cord-014597-66vd2mdu 774 2 : : : cord-014597-66vd2mdu 775 1 Capture capture NN cord-014597-66vd2mdu 775 2 strategies strategy NNS cord-014597-66vd2mdu 775 3 were be VBD cord-014597-66vd2mdu 775 4 evaluated evaluate VBN cord-014597-66vd2mdu 775 5 from from IN cord-014597-66vd2mdu 775 6 the the DT cord-014597-66vd2mdu 775 7 point point NN cord-014597-66vd2mdu 775 8 of of IN cord-014597-66vd2mdu 775 9 view view NN cord-014597-66vd2mdu 775 10 of of IN cord-014597-66vd2mdu 775 11 simplification simplification NN cord-014597-66vd2mdu 775 12 of of IN cord-014597-66vd2mdu 775 13 downstream downstream JJ cord-014597-66vd2mdu 775 14 operations operation NNS cord-014597-66vd2mdu 775 15 , , , cord-014597-66vd2mdu 775 16 with with IN cord-014597-66vd2mdu 775 17 HCP HCP NNP cord-014597-66vd2mdu 775 18 impurities impurity NNS cord-014597-66vd2mdu 775 19 content content NN cord-014597-66vd2mdu 775 20 monitored monitor VBN cord-014597-66vd2mdu 775 21 as as IN cord-014597-66vd2mdu 775 22 a a DT cord-014597-66vd2mdu 775 23 key key JJ cord-014597-66vd2mdu 775 24 performance performance NN cord-014597-66vd2mdu 775 25 indicator indicator NN cord-014597-66vd2mdu 775 26 . . . cord-014597-66vd2mdu 776 1 -Protein -protein RB cord-014597-66vd2mdu 777 1 A a DT cord-014597-66vd2mdu 777 2 affinity affinity NN cord-014597-66vd2mdu 777 3 chromatography chromatography NN cord-014597-66vd2mdu 777 4 : : : cord-014597-66vd2mdu 778 1 Advanced advanced JJ cord-014597-66vd2mdu 778 2 harvest harvest NN cord-014597-66vd2mdu 778 3 clarification clarification NN cord-014597-66vd2mdu 778 4 enabled enable VBD cord-014597-66vd2mdu 778 5 major major JJ cord-014597-66vd2mdu 778 6 improvements improvement NNS cord-014597-66vd2mdu 778 7 in in IN cord-014597-66vd2mdu 778 8 affinity affinity NN cord-014597-66vd2mdu 778 9 capture capture NN cord-014597-66vd2mdu 778 10 , , , cord-014597-66vd2mdu 778 11 in in IN cord-014597-66vd2mdu 778 12 terms term NNS cord-014597-66vd2mdu 778 13 of of IN cord-014597-66vd2mdu 778 14 eluate eluate JJ cord-014597-66vd2mdu 778 15 purity purity NN cord-014597-66vd2mdu 778 16 and and CC cord-014597-66vd2mdu 778 17 reduction reduction NN cord-014597-66vd2mdu 778 18 of of IN cord-014597-66vd2mdu 778 19 host host NN cord-014597-66vd2mdu 778 20 cell cell NN cord-014597-66vd2mdu 778 21 impurities impurity NNS cord-014597-66vd2mdu 778 22 ( ( -LRB- cord-014597-66vd2mdu 778 23 < < NNP cord-014597-66vd2mdu 778 24 35 35 CD cord-014597-66vd2mdu 778 25 ppm ppm NN cord-014597-66vd2mdu 778 26 in in IN cord-014597-66vd2mdu 778 27 all all DT cord-014597-66vd2mdu 778 28 conditions condition NNS cord-014597-66vd2mdu 778 29 tested test VBN cord-014597-66vd2mdu 778 30 ) ) -RRB- cord-014597-66vd2mdu 778 31 . . . cord-014597-66vd2mdu 779 1 ( ( -LRB- cord-014597-66vd2mdu 779 2 Fig Fig NNP cord-014597-66vd2mdu 779 3 . . NNP cord-014597-66vd2mdu 779 4 1 1 CD cord-014597-66vd2mdu 779 5 ) ) -RRB- cord-014597-66vd2mdu 779 6 . . . cord-014597-66vd2mdu 780 1 -Cation -cation NN cord-014597-66vd2mdu 780 2 exchange exchange NN cord-014597-66vd2mdu 780 3 chromatography chromatography NN cord-014597-66vd2mdu 780 4 : : : cord-014597-66vd2mdu 780 5 CEx CEx NNS cord-014597-66vd2mdu 780 6 allows allow VBZ cord-014597-66vd2mdu 780 7 higher high JJR cord-014597-66vd2mdu 780 8 capacities capacity NNS cord-014597-66vd2mdu 780 9 ( ( -LRB- cord-014597-66vd2mdu 780 10 > > VBZ cord-014597-66vd2mdu 780 11 100 100 CD cord-014597-66vd2mdu 780 12 g g NN cord-014597-66vd2mdu 780 13 / / SYM cord-014597-66vd2mdu 780 14 L L NNP cord-014597-66vd2mdu 780 15 ) ) -RRB- cord-014597-66vd2mdu 780 16 than than IN cord-014597-66vd2mdu 780 17 protein protein NN cord-014597-66vd2mdu 780 18 A A NNP cord-014597-66vd2mdu 780 19 , , , cord-014597-66vd2mdu 780 20 whilst whilst IN cord-014597-66vd2mdu 780 21 being be VBG cord-014597-66vd2mdu 780 22 more more RBR cord-014597-66vd2mdu 780 23 affordable affordable JJ cord-014597-66vd2mdu 780 24 ( ( -LRB- cord-014597-66vd2mdu 780 25 from from IN cord-014597-66vd2mdu 780 26 2-to 2-to CD cord-014597-66vd2mdu 780 27 6-fold 6-fold CD cord-014597-66vd2mdu 780 28 cheaper cheap JJR cord-014597-66vd2mdu 780 29 ) ) -RRB- cord-014597-66vd2mdu 780 30 . . . cord-014597-66vd2mdu 781 1 Low low JJ cord-014597-66vd2mdu 781 2 residual residual JJ cord-014597-66vd2mdu 781 3 HCP HCP NNP cord-014597-66vd2mdu 781 4 ( ( -LRB- cord-014597-66vd2mdu 781 5 < < XX cord-014597-66vd2mdu 781 6 500 500 CD cord-014597-66vd2mdu 781 7 ppm ppm NN cord-014597-66vd2mdu 781 8 ) ) -RRB- cord-014597-66vd2mdu 781 9 was be VBD cord-014597-66vd2mdu 781 10 observed observe VBN cord-014597-66vd2mdu 781 11 with with IN cord-014597-66vd2mdu 781 12 all all DT cord-014597-66vd2mdu 781 13 CEx CEx NNS cord-014597-66vd2mdu 781 14 resins resin NNS cord-014597-66vd2mdu 781 15 tested test VBN cord-014597-66vd2mdu 781 16 . . . cord-014597-66vd2mdu 782 1 Without without IN cord-014597-66vd2mdu 782 2 harvest harvest NN cord-014597-66vd2mdu 782 3 treatment treatment NN cord-014597-66vd2mdu 782 4 and and CC cord-014597-66vd2mdu 782 5 clarification clarification NN cord-014597-66vd2mdu 782 6 preceding precede VBG cord-014597-66vd2mdu 782 7 the the DT cord-014597-66vd2mdu 782 8 capture capture NN cord-014597-66vd2mdu 782 9 studies study NNS cord-014597-66vd2mdu 782 10 ( ( -LRB- cord-014597-66vd2mdu 782 11 either either CC cord-014597-66vd2mdu 782 12 affinity affinity NN cord-014597-66vd2mdu 782 13 or or CC cord-014597-66vd2mdu 782 14 CEx CEx NNS cord-014597-66vd2mdu 782 15 ) ) -RRB- cord-014597-66vd2mdu 782 16 , , , cord-014597-66vd2mdu 782 17 results result NNS cord-014597-66vd2mdu 782 18 showed show VBD cord-014597-66vd2mdu 782 19 a a DT cord-014597-66vd2mdu 782 20 lower low JJR cord-014597-66vd2mdu 782 21 binding binding NN cord-014597-66vd2mdu 782 22 capacity capacity NN cord-014597-66vd2mdu 782 23 of of IN cord-014597-66vd2mdu 782 24 the the DT cord-014597-66vd2mdu 782 25 resin resin NN cord-014597-66vd2mdu 782 26 , , , cord-014597-66vd2mdu 782 27 a a DT cord-014597-66vd2mdu 782 28 higher high JJR cord-014597-66vd2mdu 782 29 content content NN cord-014597-66vd2mdu 782 30 of of IN cord-014597-66vd2mdu 782 31 HCP HCP NNP cord-014597-66vd2mdu 782 32 in in IN cord-014597-66vd2mdu 782 33 the the DT cord-014597-66vd2mdu 782 34 eluate eluate NN cord-014597-66vd2mdu 782 35 ( ( -LRB- cord-014597-66vd2mdu 782 36 up up IN cord-014597-66vd2mdu 782 37 to to TO cord-014597-66vd2mdu 782 38 2000 2000 CD cord-014597-66vd2mdu 782 39 ppm ppm NN cord-014597-66vd2mdu 782 40 ) ) -RRB- cord-014597-66vd2mdu 782 41 , , , cord-014597-66vd2mdu 782 42 a a DT cord-014597-66vd2mdu 782 43 higher high JJR cord-014597-66vd2mdu 782 44 content content NN cord-014597-66vd2mdu 782 45 of of IN cord-014597-66vd2mdu 782 46 HMW HMW NNP cord-014597-66vd2mdu 782 47 species specie NNS cord-014597-66vd2mdu 782 48 in in IN cord-014597-66vd2mdu 782 49 the the DT cord-014597-66vd2mdu 782 50 elution elution NN cord-014597-66vd2mdu 782 51 fraction fraction NN cord-014597-66vd2mdu 782 52 ( ( -LRB- cord-014597-66vd2mdu 782 53 up up IN cord-014597-66vd2mdu 782 54 to to TO cord-014597-66vd2mdu 782 55 3-fold 3-fold CD cord-014597-66vd2mdu 782 56 higher high JJR cord-014597-66vd2mdu 782 57 ) ) -RRB- cord-014597-66vd2mdu 782 58 and and CC cord-014597-66vd2mdu 782 59 a a DT cord-014597-66vd2mdu 782 60 significant significant JJ cord-014597-66vd2mdu 782 61 turbidity turbidity NN cord-014597-66vd2mdu 782 62 of of IN cord-014597-66vd2mdu 782 63 the the DT cord-014597-66vd2mdu 782 64 neutralized neutralize VBN cord-014597-66vd2mdu 782 65 eluate eluate NN cord-014597-66vd2mdu 782 66 . . . cord-014597-66vd2mdu 783 1 -Continuous -continuous JJ cord-014597-66vd2mdu 783 2 multicolumn multicolumn NN cord-014597-66vd2mdu 783 3 chromatography chromatography NN cord-014597-66vd2mdu 783 4 : : : cord-014597-66vd2mdu 783 5 Further further JJ cord-014597-66vd2mdu 783 6 options option NNS cord-014597-66vd2mdu 783 7 to to TO cord-014597-66vd2mdu 783 8 increase increase VB cord-014597-66vd2mdu 783 9 cost cost NN cord-014597-66vd2mdu 783 10 efficiency efficiency NN cord-014597-66vd2mdu 783 11 include include VBP cord-014597-66vd2mdu 783 12 using use VBG cord-014597-66vd2mdu 783 13 a a DT cord-014597-66vd2mdu 783 14 continuous continuous JJ cord-014597-66vd2mdu 783 15 multicolumn multicolumn NN cord-014597-66vd2mdu 783 16 setup setup NN cord-014597-66vd2mdu 783 17 ( ( -LRB- cord-014597-66vd2mdu 783 18 Table table NN cord-014597-66vd2mdu 783 19 1 1 CD cord-014597-66vd2mdu 783 20 ) ) -RRB- cord-014597-66vd2mdu 783 21 . . . cord-014597-66vd2mdu 784 1 Two two CD cord-014597-66vd2mdu 784 2 models model NNS cord-014597-66vd2mdu 784 3 were be VBD cord-014597-66vd2mdu 784 4 assessed assess VBN cord-014597-66vd2mdu 784 5 based base VBN cord-014597-66vd2mdu 784 6 on on IN cord-014597-66vd2mdu 784 7 two two CD cord-014597-66vd2mdu 784 8 different different JJ cord-014597-66vd2mdu 784 9 static static JJ cord-014597-66vd2mdu 784 10 binding binding NN cord-014597-66vd2mdu 784 11 capacities capacity NNS cord-014597-66vd2mdu 784 12 ( ( -LRB- cord-014597-66vd2mdu 784 13 SBC SBC NNP cord-014597-66vd2mdu 784 14 ) ) -RRB- cord-014597-66vd2mdu 784 15 , , , cord-014597-66vd2mdu 784 16 demonstrating demonstrate VBG cord-014597-66vd2mdu 784 17 that that IN cord-014597-66vd2mdu 784 18 4 4 CD cord-014597-66vd2mdu 784 19 to to TO cord-014597-66vd2mdu 784 20 6 6 CD cord-014597-66vd2mdu 784 21 columns column NNS cord-014597-66vd2mdu 784 22 of of IN cord-014597-66vd2mdu 784 23 100ml 100ml NNP cord-014597-66vd2mdu 784 24 were be VBD cord-014597-66vd2mdu 784 25 able able JJ cord-014597-66vd2mdu 784 26 to to TO cord-014597-66vd2mdu 784 27 process process VB cord-014597-66vd2mdu 784 28 a a DT cord-014597-66vd2mdu 784 29 200L 200l CD cord-014597-66vd2mdu 784 30 production production NN cord-014597-66vd2mdu 784 31 in in IN cord-014597-66vd2mdu 784 32 less less JJR cord-014597-66vd2mdu 784 33 than than IN cord-014597-66vd2mdu 784 34 24h 24h NNS cord-014597-66vd2mdu 784 35 . . . cord-014597-66vd2mdu 785 1 This this DT cord-014597-66vd2mdu 785 2 method method NN cord-014597-66vd2mdu 785 3 provides provide VBZ cord-014597-66vd2mdu 785 4 a a DT cord-014597-66vd2mdu 785 5 great great JJ cord-014597-66vd2mdu 785 6 opportunity opportunity NN cord-014597-66vd2mdu 785 7 for for IN cord-014597-66vd2mdu 785 8 designing design VBG cord-014597-66vd2mdu 785 9 simplified simplified JJ cord-014597-66vd2mdu 785 10 and and CC cord-014597-66vd2mdu 785 11 low low JJ cord-014597-66vd2mdu 785 12 footprint footprint NN cord-014597-66vd2mdu 785 13 Mabs Mabs NNP cord-014597-66vd2mdu 785 14 DSP DSP NNP cord-014597-66vd2mdu 785 15 processes process NNS cord-014597-66vd2mdu 785 16 , , , cord-014597-66vd2mdu 785 17 while while IN cord-014597-66vd2mdu 785 18 maintaining maintain VBG cord-014597-66vd2mdu 785 19 similar similar JJ cord-014597-66vd2mdu 785 20 or or CC cord-014597-66vd2mdu 785 21 achieving achieve VBG cord-014597-66vd2mdu 785 22 superior superior JJ cord-014597-66vd2mdu 785 23 quality quality NN cord-014597-66vd2mdu 785 24 profile profile NN cord-014597-66vd2mdu 785 25 compared compare VBN cord-014597-66vd2mdu 785 26 to to IN cord-014597-66vd2mdu 785 27 standard standard JJ cord-014597-66vd2mdu 785 28 approaches approach NNS cord-014597-66vd2mdu 785 29 : : : cord-014597-66vd2mdu 786 1 -Harvests -harvest NNS cord-014597-66vd2mdu 786 2 treatments treatment NNS cord-014597-66vd2mdu 786 3 followed follow VBN cord-014597-66vd2mdu 786 4 by by IN cord-014597-66vd2mdu 786 5 depth depth NN cord-014597-66vd2mdu 786 6 filtration filtration NN cord-014597-66vd2mdu 786 7 proved prove VBN cord-014597-66vd2mdu 786 8 to to TO cord-014597-66vd2mdu 786 9 be be VB cord-014597-66vd2mdu 786 10 a a DT cord-014597-66vd2mdu 786 11 cost cost NN cord-014597-66vd2mdu 786 12 - - HYPH cord-014597-66vd2mdu 786 13 efficient efficient JJ cord-014597-66vd2mdu 786 14 way way NN cord-014597-66vd2mdu 786 15 to to TO cord-014597-66vd2mdu 786 16 obtain obtain VB cord-014597-66vd2mdu 786 17 pretreated pretreate VBN cord-014597-66vd2mdu 786 18 feed feed NN cord-014597-66vd2mdu 786 19 and and CC cord-014597-66vd2mdu 786 20 minimize minimize VB cord-014597-66vd2mdu 786 21 the the DT cord-014597-66vd2mdu 786 22 burden burden NN cord-014597-66vd2mdu 786 23 on on IN cord-014597-66vd2mdu 786 24 downstream downstream JJ cord-014597-66vd2mdu 786 25 operations operation NNS cord-014597-66vd2mdu 786 26 . . . cord-014597-66vd2mdu 787 1 -Protein -protein RB cord-014597-66vd2mdu 788 1 A a DT cord-014597-66vd2mdu 788 2 resins resin NNS cord-014597-66vd2mdu 788 3 exhibited exhibit VBD cord-014597-66vd2mdu 788 4 advantages advantage NNS cord-014597-66vd2mdu 788 5 of of IN cord-014597-66vd2mdu 788 6 extracting extract VBG cord-014597-66vd2mdu 788 7 key key JJ cord-014597-66vd2mdu 788 8 contaminants contaminant NNS cord-014597-66vd2mdu 788 9 during during IN cord-014597-66vd2mdu 788 10 harvest harvest NN cord-014597-66vd2mdu 788 11 treatment treatment NN cord-014597-66vd2mdu 788 12 , , , cord-014597-66vd2mdu 788 13 while while IN cord-014597-66vd2mdu 788 14 CAEX CAEX NNP cord-014597-66vd2mdu 788 15 confirmed confirm VBD cord-014597-66vd2mdu 788 16 to to TO cord-014597-66vd2mdu 788 17 be be VB cord-014597-66vd2mdu 788 18 a a DT cord-014597-66vd2mdu 788 19 competitive competitive JJ cord-014597-66vd2mdu 788 20 capture capture NN cord-014597-66vd2mdu 788 21 strategy strategy NN cord-014597-66vd2mdu 788 22 . . . cord-014597-66vd2mdu 789 1 -Switching -switche VBG cord-014597-66vd2mdu 789 2 from from IN cord-014597-66vd2mdu 789 3 batch batch NN cord-014597-66vd2mdu 789 4 to to IN cord-014597-66vd2mdu 789 5 continuous continuous JJ cord-014597-66vd2mdu 789 6 multicolumn multicolumn NN cord-014597-66vd2mdu 789 7 mode mode NN cord-014597-66vd2mdu 789 8 allowed allow VBN cord-014597-66vd2mdu 789 9 to to TO cord-014597-66vd2mdu 789 10 process process VB cord-014597-66vd2mdu 789 11 a a DT cord-014597-66vd2mdu 789 12 complete complete JJ cord-014597-66vd2mdu 789 13 batch batch NN cord-014597-66vd2mdu 789 14 in in IN cord-014597-66vd2mdu 789 15 less less JJR cord-014597-66vd2mdu 789 16 than than IN cord-014597-66vd2mdu 789 17 24 24 CD cord-014597-66vd2mdu 789 18 hours hour NNS cord-014597-66vd2mdu 789 19 , , , cord-014597-66vd2mdu 789 20 requiring require VBG cord-014597-66vd2mdu 789 21 lower low JJR cord-014597-66vd2mdu 789 22 media medium NNS cord-014597-66vd2mdu 789 23 and and CC cord-014597-66vd2mdu 789 24 resins resin NNS cord-014597-66vd2mdu 789 25 volumes volume NNS cord-014597-66vd2mdu 789 26 . . . cord-014597-66vd2mdu 790 1 Followed follow VBN cord-014597-66vd2mdu 790 2 by by IN cord-014597-66vd2mdu 790 3 a a DT cord-014597-66vd2mdu 790 4 single single JJ cord-014597-66vd2mdu 790 5 polishing polishing NN cord-014597-66vd2mdu 790 6 step step NN cord-014597-66vd2mdu 790 7 , , , cord-014597-66vd2mdu 790 8 such such JJ cord-014597-66vd2mdu 790 9 process process NN cord-014597-66vd2mdu 790 10 set set VBN cord-014597-66vd2mdu 790 11 - - HYPH cord-014597-66vd2mdu 790 12 up up NN cord-014597-66vd2mdu 790 13 strongly strongly RB cord-014597-66vd2mdu 790 14 supports support VBZ cord-014597-66vd2mdu 790 15 the the DT cord-014597-66vd2mdu 790 16 reduction reduction NN cord-014597-66vd2mdu 790 17 of of IN cord-014597-66vd2mdu 790 18 operations operation NNS cord-014597-66vd2mdu 790 19 required require VBN cord-014597-66vd2mdu 790 20 to to TO cord-014597-66vd2mdu 790 21 deliver deliver VB cord-014597-66vd2mdu 790 22 a a DT cord-014597-66vd2mdu 790 23 high high JJ cord-014597-66vd2mdu 790 24 - - HYPH cord-014597-66vd2mdu 790 25 quality quality NN cord-014597-66vd2mdu 790 26 product product NN cord-014597-66vd2mdu 790 27 . . . cord-014597-66vd2mdu 791 1 Analyses analysis NNS cord-014597-66vd2mdu 791 2 of of IN cord-014597-66vd2mdu 791 3 product product NN cord-014597-66vd2mdu 791 4 quality quality NN cord-014597-66vd2mdu 791 5 of of IN cord-014597-66vd2mdu 791 6 complex complex JJ cord-014597-66vd2mdu 791 7 polymeric polymeric JJ cord-014597-66vd2mdu 791 8 IgM igm NN cord-014597-66vd2mdu 791 9 produced produce VBN cord-014597-66vd2mdu 791 10 by by IN cord-014597-66vd2mdu 791 11 CHO CHO NNP cord-014597-66vd2mdu 791 12 cells cell NNS cord-014597-66vd2mdu 792 1 Background Background NNP cord-014597-66vd2mdu 792 2 Immunoglobulin Immunoglobulin NNP cord-014597-66vd2mdu 792 3 M M NNP cord-014597-66vd2mdu 792 4 ( ( -LRB- cord-014597-66vd2mdu 792 5 IgM IgM NNP cord-014597-66vd2mdu 792 6 ) ) -RRB- cord-014597-66vd2mdu 792 7 antibodies antibody NNS cord-014597-66vd2mdu 792 8 are be VBP cord-014597-66vd2mdu 792 9 secreted secrete VBN cord-014597-66vd2mdu 792 10 by by IN cord-014597-66vd2mdu 792 11 B b NN cord-014597-66vd2mdu 792 12 cells cell NNS cord-014597-66vd2mdu 792 13 as as IN cord-014597-66vd2mdu 792 14 the the DT cord-014597-66vd2mdu 792 15 first first JJ cord-014597-66vd2mdu 792 16 defense defense NN cord-014597-66vd2mdu 792 17 against against IN cord-014597-66vd2mdu 792 18 invading invade VBG cord-014597-66vd2mdu 792 19 pathogens pathogen NNS cord-014597-66vd2mdu 792 20 during during IN cord-014597-66vd2mdu 792 21 primary primary JJ cord-014597-66vd2mdu 792 22 immune immune JJ cord-014597-66vd2mdu 792 23 response response NN cord-014597-66vd2mdu 792 24 . . . cord-014597-66vd2mdu 793 1 Some some DT cord-014597-66vd2mdu 793 2 IgM IgM NNP cord-014597-66vd2mdu 793 3 antibodies antibody NNS cord-014597-66vd2mdu 793 4 already already RB cord-014597-66vd2mdu 793 5 gained gain VBD cord-014597-66vd2mdu 793 6 the the DT cord-014597-66vd2mdu 793 7 orphan orphan NN cord-014597-66vd2mdu 793 8 drug drug NN cord-014597-66vd2mdu 793 9 status status NN cord-014597-66vd2mdu 793 10 , , , cord-014597-66vd2mdu 793 11 which which WDT cord-014597-66vd2mdu 793 12 shows show VBZ cord-014597-66vd2mdu 793 13 their -PRON- PRP$ cord-014597-66vd2mdu 793 14 unique unique JJ cord-014597-66vd2mdu 793 15 capability capability NN cord-014597-66vd2mdu 793 16 in in IN cord-014597-66vd2mdu 793 17 therapy therapy NN cord-014597-66vd2mdu 793 18 of of IN cord-014597-66vd2mdu 793 19 rare rare JJ cord-014597-66vd2mdu 793 20 diseases disease NNS cord-014597-66vd2mdu 793 21 . . . cord-014597-66vd2mdu 794 1 Potential potential JJ cord-014597-66vd2mdu 794 2 fields field NNS cord-014597-66vd2mdu 794 3 for for IN cord-014597-66vd2mdu 794 4 applications application NNS cord-014597-66vd2mdu 794 5 are be VBP cord-014597-66vd2mdu 794 6 discovered discover VBN cord-014597-66vd2mdu 794 7 with with IN cord-014597-66vd2mdu 794 8 increasing increase VBG cord-014597-66vd2mdu 794 9 knowledge knowledge NN cord-014597-66vd2mdu 794 10 about about IN cord-014597-66vd2mdu 794 11 these these DT cord-014597-66vd2mdu 794 12 molecules molecule NNS cord-014597-66vd2mdu 794 13 . . . cord-014597-66vd2mdu 795 1 It -PRON- PRP cord-014597-66vd2mdu 795 2 seems seem VBZ cord-014597-66vd2mdu 795 3 that that IN cord-014597-66vd2mdu 795 4 the the DT cord-014597-66vd2mdu 795 5 most most RBS cord-014597-66vd2mdu 795 6 active active JJ cord-014597-66vd2mdu 795 7 forms form NNS cord-014597-66vd2mdu 795 8 are be VBP cord-014597-66vd2mdu 795 9 pentameric pentameric JJ cord-014597-66vd2mdu 795 10 and and CC cord-014597-66vd2mdu 795 11 hexameric hexameric JJ cord-014597-66vd2mdu 795 12 IgMs IgMs '' cord-014597-66vd2mdu 795 13 . . . cord-014597-66vd2mdu 796 1 Unfortunately unfortunately RB cord-014597-66vd2mdu 796 2 , , , cord-014597-66vd2mdu 796 3 recombinant recombinant JJ cord-014597-66vd2mdu 796 4 production production NN cord-014597-66vd2mdu 796 5 of of IN cord-014597-66vd2mdu 796 6 IgMs IgMs NNP cord-014597-66vd2mdu 796 7 is be VBZ cord-014597-66vd2mdu 796 8 rather rather RB cord-014597-66vd2mdu 796 9 difficult difficult JJ cord-014597-66vd2mdu 796 10 as as IN cord-014597-66vd2mdu 796 11 secretion secretion NN cord-014597-66vd2mdu 796 12 and and CC cord-014597-66vd2mdu 796 13 correct correct JJ cord-014597-66vd2mdu 796 14 polymer polymer NN cord-014597-66vd2mdu 796 15 formation formation NN cord-014597-66vd2mdu 796 16 results result NNS cord-014597-66vd2mdu 796 17 in in IN cord-014597-66vd2mdu 796 18 low low JJ cord-014597-66vd2mdu 796 19 expression expression NN cord-014597-66vd2mdu 796 20 yields yield NNS cord-014597-66vd2mdu 796 21 and and CC cord-014597-66vd2mdu 796 22 mixtures mixture NNS cord-014597-66vd2mdu 796 23 of of IN cord-014597-66vd2mdu 796 24 polymers polymer NNS cord-014597-66vd2mdu 796 25 . . . cord-014597-66vd2mdu 797 1 We -PRON- PRP cord-014597-66vd2mdu 797 2 established establish VBD cord-014597-66vd2mdu 797 3 stable stable JJ cord-014597-66vd2mdu 797 4 producing produce VBG cord-014597-66vd2mdu 797 5 Chinese chinese JJ cord-014597-66vd2mdu 797 6 hamster hamster NN cord-014597-66vd2mdu 797 7 ovary ovary NN cord-014597-66vd2mdu 798 1 ( ( -LRB- cord-014597-66vd2mdu 798 2 CHO CHO NNP cord-014597-66vd2mdu 798 3 ) ) -RRB- cord-014597-66vd2mdu 798 4 DG44 DG44 NNP cord-014597-66vd2mdu 798 5 cell cell NN cord-014597-66vd2mdu 798 6 lines line NNS cord-014597-66vd2mdu 798 7 to to TO cord-014597-66vd2mdu 798 8 analyze analyze VB cord-014597-66vd2mdu 798 9 cellular cellular JJ cord-014597-66vd2mdu 798 10 and and CC cord-014597-66vd2mdu 798 11 extracellular extracellular JJ cord-014597-66vd2mdu 798 12 factors factor NNS cord-014597-66vd2mdu 798 13 that that WDT cord-014597-66vd2mdu 798 14 influence influence VBP cord-014597-66vd2mdu 798 15 quantity quantity NN cord-014597-66vd2mdu 798 16 and and CC cord-014597-66vd2mdu 798 17 quality quality NN cord-014597-66vd2mdu 798 18 of of IN cord-014597-66vd2mdu 798 19 the the DT cord-014597-66vd2mdu 798 20 produced produce VBN cord-014597-66vd2mdu 798 21 recombinant recombinant JJ cord-014597-66vd2mdu 798 22 polymeric polymeric JJ cord-014597-66vd2mdu 798 23 IgM IgM NNP cord-014597-66vd2mdu 798 24 in in IN cord-014597-66vd2mdu 798 25 future future JJ cord-014597-66vd2mdu 798 26 studies study NNS cord-014597-66vd2mdu 798 27 [ [ -LRB- cord-014597-66vd2mdu 798 28 1 1 CD cord-014597-66vd2mdu 798 29 ] ] -RRB- cord-014597-66vd2mdu 798 30 . . . cord-014597-66vd2mdu 799 1 One one CD cord-014597-66vd2mdu 799 2 quality quality NN cord-014597-66vd2mdu 799 3 parameter parameter NN cord-014597-66vd2mdu 799 4 is be VBZ cord-014597-66vd2mdu 799 5 polymer polymer NN cord-014597-66vd2mdu 799 6 distribution distribution NN cord-014597-66vd2mdu 799 7 , , , cord-014597-66vd2mdu 799 8 which which WDT cord-014597-66vd2mdu 799 9 can can MD cord-014597-66vd2mdu 799 10 be be VB cord-014597-66vd2mdu 799 11 measured measure VBN cord-014597-66vd2mdu 799 12 directly directly RB cord-014597-66vd2mdu 799 13 in in IN cord-014597-66vd2mdu 799 14 cell cell NN cord-014597-66vd2mdu 799 15 culture culture NN cord-014597-66vd2mdu 799 16 supernatant supernatant VBN cord-014597-66vd2mdu 799 17 using use VBG cord-014597-66vd2mdu 799 18 densitometric densitometric JJ cord-014597-66vd2mdu 799 19 analyses analysis NNS cord-014597-66vd2mdu 799 20 [ [ -LRB- cord-014597-66vd2mdu 799 21 2 2 CD cord-014597-66vd2mdu 799 22 ] ] -RRB- cord-014597-66vd2mdu 799 23 . . . cord-014597-66vd2mdu 800 1 Additionally additionally RB cord-014597-66vd2mdu 800 2 , , , cord-014597-66vd2mdu 800 3 we -PRON- PRP cord-014597-66vd2mdu 800 4 developed develop VBD cord-014597-66vd2mdu 800 5 a a DT cord-014597-66vd2mdu 800 6 very very RB cord-014597-66vd2mdu 800 7 efficient efficient JJ cord-014597-66vd2mdu 800 8 single single JJ cord-014597-66vd2mdu 800 9 - - HYPH cord-014597-66vd2mdu 800 10 step step NN cord-014597-66vd2mdu 800 11 - - HYPH cord-014597-66vd2mdu 800 12 affinity affinity NN cord-014597-66vd2mdu 800 13 purification purification NN cord-014597-66vd2mdu 800 14 strategy strategy NN cord-014597-66vd2mdu 800 15 using use VBG cord-014597-66vd2mdu 800 16 the the DT cord-014597-66vd2mdu 800 17 POROS POROS NNP cord-014597-66vd2mdu 800 18 CaptureSelect CaptureSelect NNP cord-014597-66vd2mdu 800 19 IgM IgM NNP cord-014597-66vd2mdu 800 20 Affinity Affinity NNP cord-014597-66vd2mdu 800 21 Matrix Matrix NNP cord-014597-66vd2mdu 800 22 to to TO cord-014597-66vd2mdu 800 23 analyze analyze VB cord-014597-66vd2mdu 800 24 pure pure JJ cord-014597-66vd2mdu 800 25 IgMs IgMs NNP cord-014597-66vd2mdu 800 26 . . . cord-014597-66vd2mdu 801 1 For for IN cord-014597-66vd2mdu 801 2 more more RBR cord-014597-66vd2mdu 801 3 precise precise JJ cord-014597-66vd2mdu 801 4 measurements measurement NNS cord-014597-66vd2mdu 801 5 of of IN cord-014597-66vd2mdu 801 6 the the DT cord-014597-66vd2mdu 801 7 IgM IgM NNP cord-014597-66vd2mdu 801 8 isoform isoform NNP cord-014597-66vd2mdu 801 9 distribution distribution NN cord-014597-66vd2mdu 801 10 we -PRON- PRP cord-014597-66vd2mdu 801 11 separated separate VBD cord-014597-66vd2mdu 801 12 the the DT cord-014597-66vd2mdu 801 13 purified purify VBN cord-014597-66vd2mdu 801 14 polymers polymer NNS cord-014597-66vd2mdu 801 15 by by IN cord-014597-66vd2mdu 801 16 high high JJ cord-014597-66vd2mdu 801 17 performance performance NN cord-014597-66vd2mdu 801 18 liquid liquid NN cord-014597-66vd2mdu 801 19 size size NN cord-014597-66vd2mdu 801 20 exclusion exclusion NN cord-014597-66vd2mdu 801 21 chromatography chromatography NN cord-014597-66vd2mdu 801 22 ( ( -LRB- cord-014597-66vd2mdu 801 23 SEC SEC NNP cord-014597-66vd2mdu 801 24 HPLC HPLC NNP cord-014597-66vd2mdu 801 25 ) ) -RRB- cord-014597-66vd2mdu 801 26 . . . cord-014597-66vd2mdu 802 1 Our -PRON- PRP$ cord-014597-66vd2mdu 802 2 CHO CHO NNP cord-014597-66vd2mdu 802 3 DG44 DG44 NNP cord-014597-66vd2mdu 802 4 cell cell NN cord-014597-66vd2mdu 802 5 lines line NNS cord-014597-66vd2mdu 802 6 grow grow VBP cord-014597-66vd2mdu 802 7 to to TO cord-014597-66vd2mdu 802 8 peak peak VB cord-014597-66vd2mdu 802 9 cell cell NN cord-014597-66vd2mdu 802 10 concentration concentration NN cord-014597-66vd2mdu 802 11 of of IN cord-014597-66vd2mdu 802 12 4.5x10 4.5x10 CD cord-014597-66vd2mdu 802 13 6 6 CD cord-014597-66vd2mdu 802 14 cells cell NNS cord-014597-66vd2mdu 802 15 / / SYM cord-014597-66vd2mdu 802 16 mL ml NN cord-014597-66vd2mdu 802 17 in in IN cord-014597-66vd2mdu 802 18 Erlenmeyer Erlenmeyer NNP cord-014597-66vd2mdu 802 19 flasks flask NNS cord-014597-66vd2mdu 802 20 and and CC cord-014597-66vd2mdu 802 21 4.0x10 4.0x10 CD cord-014597-66vd2mdu 802 22 6 6 CD cord-014597-66vd2mdu 802 23 cells cell NNS cord-014597-66vd2mdu 802 24 / / SYM cord-014597-66vd2mdu 802 25 mL ml NN cord-014597-66vd2mdu 802 26 in in IN cord-014597-66vd2mdu 802 27 bioreactors bioreactor NNS cord-014597-66vd2mdu 802 28 . . . cord-014597-66vd2mdu 803 1 Similar similar JJ cord-014597-66vd2mdu 803 2 productivity productivity NN cord-014597-66vd2mdu 803 3 of of IN cord-014597-66vd2mdu 803 4 approximately approximately RB cord-014597-66vd2mdu 803 5 50 50 CD cord-014597-66vd2mdu 803 6 mg mg NNP cord-014597-66vd2mdu 803 7 / / SYM cord-014597-66vd2mdu 803 8 L L NNP cord-014597-66vd2mdu 803 9 was be VBD cord-014597-66vd2mdu 803 10 observed observe VBN cord-014597-66vd2mdu 803 11 for for IN cord-014597-66vd2mdu 803 12 cells cell NNS cord-014597-66vd2mdu 803 13 cultivated cultivate VBN cord-014597-66vd2mdu 803 14 in in IN cord-014597-66vd2mdu 803 15 both both DT cord-014597-66vd2mdu 803 16 cultivation cultivation NN cord-014597-66vd2mdu 803 17 vessels vessel NNS cord-014597-66vd2mdu 803 18 in in IN cord-014597-66vd2mdu 803 19 a a DT cord-014597-66vd2mdu 803 20 nonoptimized nonoptimized JJ cord-014597-66vd2mdu 803 21 batch batch NN cord-014597-66vd2mdu 803 22 culture culture NN cord-014597-66vd2mdu 803 23 using use VBG cord-014597-66vd2mdu 803 24 chemically chemically RB cord-014597-66vd2mdu 803 25 defined define VBN cord-014597-66vd2mdu 803 26 media medium NNS cord-014597-66vd2mdu 803 27 . . . cord-014597-66vd2mdu 804 1 Analysing analyse VBG cord-014597-66vd2mdu 804 2 how how WRB cord-014597-66vd2mdu 804 3 cultivation cultivation NN cord-014597-66vd2mdu 804 4 conditions condition NNS cord-014597-66vd2mdu 804 5 affect affect VBP cord-014597-66vd2mdu 804 6 the the DT cord-014597-66vd2mdu 804 7 fraction fraction NN cord-014597-66vd2mdu 804 8 of of IN cord-014597-66vd2mdu 804 9 polymers polymer NNS cord-014597-66vd2mdu 804 10 may may MD cord-014597-66vd2mdu 804 11 offer offer VB cord-014597-66vd2mdu 804 12 clues clue NNS cord-014597-66vd2mdu 804 13 about about IN cord-014597-66vd2mdu 804 14 the the DT cord-014597-66vd2mdu 804 15 assembly assembly NN cord-014597-66vd2mdu 804 16 of of IN cord-014597-66vd2mdu 804 17 polymers polymer NNS cord-014597-66vd2mdu 804 18 and and CC cord-014597-66vd2mdu 804 19 the the DT cord-014597-66vd2mdu 804 20 challenges challenge NNS cord-014597-66vd2mdu 804 21 of of IN cord-014597-66vd2mdu 804 22 IgM IgM NNP cord-014597-66vd2mdu 804 23 production production NN cord-014597-66vd2mdu 804 24 . . . cord-014597-66vd2mdu 805 1 We -PRON- PRP cord-014597-66vd2mdu 805 2 quantified quantify VBD cord-014597-66vd2mdu 805 3 polymeric polymeric JJ cord-014597-66vd2mdu 805 4 distribution distribution NN cord-014597-66vd2mdu 805 5 of of IN cord-014597-66vd2mdu 805 6 IgM IgM NNP cord-014597-66vd2mdu 805 7 directly directly RB cord-014597-66vd2mdu 805 8 in in IN cord-014597-66vd2mdu 805 9 the the DT cord-014597-66vd2mdu 805 10 supernatant supernatant NN cord-014597-66vd2mdu 805 11 using use VBG cord-014597-66vd2mdu 805 12 a a DT cord-014597-66vd2mdu 805 13 densitometric densitometric JJ cord-014597-66vd2mdu 805 14 method method NN cord-014597-66vd2mdu 805 15 [ [ -LRB- cord-014597-66vd2mdu 805 16 2 2 CD cord-014597-66vd2mdu 805 17 ] ] -RRB- cord-014597-66vd2mdu 805 18 . . . cord-014597-66vd2mdu 806 1 Cultivated cultivate VBN cord-014597-66vd2mdu 806 2 under under IN cord-014597-66vd2mdu 806 3 standard standard JJ cord-014597-66vd2mdu 806 4 conditions condition NNS cord-014597-66vd2mdu 806 5 ( ( -LRB- cord-014597-66vd2mdu 806 6 37 37 CD cord-014597-66vd2mdu 806 7 ° ° NN cord-014597-66vd2mdu 806 8 C c NN cord-014597-66vd2mdu 806 9 , , , cord-014597-66vd2mdu 806 10 pH pH NNP cord-014597-66vd2mdu 806 11 7 7 CD cord-014597-66vd2mdu 806 12 ) ) -RRB- cord-014597-66vd2mdu 807 1 IgM012 IgM012 NNP cord-014597-66vd2mdu 807 2 is be VBZ cord-014597-66vd2mdu 807 3 produced produce VBN cord-014597-66vd2mdu 807 4 as as IN cord-014597-66vd2mdu 807 5 90 90 CD cord-014597-66vd2mdu 807 6 % % NN cord-014597-66vd2mdu 807 7 pentamers pentamer NNS cord-014597-66vd2mdu 807 8 , , , cord-014597-66vd2mdu 807 9 whereas whereas IN cord-014597-66vd2mdu 807 10 IgM012_GL IgM012_GL NNP cord-014597-66vd2mdu 807 11 only only RB cord-014597-66vd2mdu 807 12 consists consist VBZ cord-014597-66vd2mdu 807 13 of of IN cord-014597-66vd2mdu 807 14 approximately approximately RB cord-014597-66vd2mdu 807 15 80 80 CD cord-014597-66vd2mdu 807 16 % % NN cord-014597-66vd2mdu 807 17 pentamers pentamer NNS cord-014597-66vd2mdu 807 18 . . . cord-014597-66vd2mdu 808 1 The the DT cord-014597-66vd2mdu 808 2 purified purify VBN cord-014597-66vd2mdu 808 3 IgM012_GL IgM012_GL NNP cord-014597-66vd2mdu 808 4 was be VBD cord-014597-66vd2mdu 808 5 analysed analyse VBN cord-014597-66vd2mdu 808 6 with with IN cord-014597-66vd2mdu 808 7 SEC SEC NNP cord-014597-66vd2mdu 808 8 - - HYPH cord-014597-66vd2mdu 808 9 HPLC HPLC NNP cord-014597-66vd2mdu 808 10 and and CC cord-014597-66vd2mdu 808 11 contained contain VBD cord-014597-66vd2mdu 808 12 81 81 CD cord-014597-66vd2mdu 808 13 % % NN cord-014597-66vd2mdu 808 14 pentamer pentamer NN cord-014597-66vd2mdu 808 15 and and CC cord-014597-66vd2mdu 808 16 19 19 CD cord-014597-66vd2mdu 808 17 % % NN cord-014597-66vd2mdu 808 18 dimer dimer NN cord-014597-66vd2mdu 808 19 , , , cord-014597-66vd2mdu 808 20 which which WDT cord-014597-66vd2mdu 808 21 is be VBZ cord-014597-66vd2mdu 808 22 comparable comparable JJ cord-014597-66vd2mdu 808 23 to to IN cord-014597-66vd2mdu 808 24 the the DT cord-014597-66vd2mdu 808 25 results result NNS cord-014597-66vd2mdu 808 26 achieved achieve VBN cord-014597-66vd2mdu 808 27 with with IN cord-014597-66vd2mdu 808 28 densitometry densitometry NNP cord-014597-66vd2mdu 808 29 . . . cord-014597-66vd2mdu 809 1 The the DT cord-014597-66vd2mdu 809 2 purification purification NN cord-014597-66vd2mdu 809 3 of of IN cord-014597-66vd2mdu 809 4 the the DT cord-014597-66vd2mdu 809 5 IgM IgM NNP cord-014597-66vd2mdu 809 6 antibodies antibody NNS cord-014597-66vd2mdu 809 7 was be VBD cord-014597-66vd2mdu 809 8 quite quite RB cord-014597-66vd2mdu 809 9 challenging challenging JJ cord-014597-66vd2mdu 809 10 as as IN cord-014597-66vd2mdu 809 11 the the DT cord-014597-66vd2mdu 809 12 manufacturer manufacturer NN cord-014597-66vd2mdu 809 13 recommend recommend VBP cord-014597-66vd2mdu 809 14 acidic acidic JJ cord-014597-66vd2mdu 809 15 elution elution NN cord-014597-66vd2mdu 809 16 , , , cord-014597-66vd2mdu 809 17 which which WDT cord-014597-66vd2mdu 809 18 led lead VBD cord-014597-66vd2mdu 809 19 to to IN cord-014597-66vd2mdu 809 20 aggregation aggregation NN cord-014597-66vd2mdu 809 21 and and CC cord-014597-66vd2mdu 809 22 inefficient inefficient JJ cord-014597-66vd2mdu 809 23 elution elution NN cord-014597-66vd2mdu 809 24 of of IN cord-014597-66vd2mdu 809 25 our -PRON- PRP$ cord-014597-66vd2mdu 809 26 model model NN cord-014597-66vd2mdu 809 27 IgMs IgMs NNP cord-014597-66vd2mdu 809 28 . . . cord-014597-66vd2mdu 810 1 Therefore therefore RB cord-014597-66vd2mdu 810 2 , , , cord-014597-66vd2mdu 810 3 we -PRON- PRP cord-014597-66vd2mdu 810 4 screened screen VBD cord-014597-66vd2mdu 810 5 for for IN cord-014597-66vd2mdu 810 6 different different JJ cord-014597-66vd2mdu 810 7 elution elution NN cord-014597-66vd2mdu 810 8 buffers buffer NNS cord-014597-66vd2mdu 810 9 that that WDT cord-014597-66vd2mdu 810 10 prevent prevent VBP cord-014597-66vd2mdu 810 11 denaturation denaturation NN cord-014597-66vd2mdu 810 12 and and CC cord-014597-66vd2mdu 810 13 aggregation aggregation NN cord-014597-66vd2mdu 810 14 . . . cord-014597-66vd2mdu 811 1 By by IN cord-014597-66vd2mdu 811 2 combining combine VBG cord-014597-66vd2mdu 811 3 high high JJ cord-014597-66vd2mdu 811 4 salt salt NN cord-014597-66vd2mdu 811 5 concentrations concentration NNS cord-014597-66vd2mdu 811 6 with with IN cord-014597-66vd2mdu 811 7 moderate moderate JJ cord-014597-66vd2mdu 811 8 pH pH NNP cord-014597-66vd2mdu 811 9 reduction reduction NN cord-014597-66vd2mdu 811 10 we -PRON- PRP cord-014597-66vd2mdu 811 11 optimized optimize VBD cord-014597-66vd2mdu 811 12 elution elution NN cord-014597-66vd2mdu 811 13 conditions condition NNS cord-014597-66vd2mdu 811 14 to to IN cord-014597-66vd2mdu 811 15 88 88 CD cord-014597-66vd2mdu 811 16 - - SYM cord-014597-66vd2mdu 811 17 99 99 CD cord-014597-66vd2mdu 811 18 % % NN cord-014597-66vd2mdu 811 19 IgM IgM NNP cord-014597-66vd2mdu 811 20 recovery recovery NN cord-014597-66vd2mdu 811 21 , , , cord-014597-66vd2mdu 811 22 which which WDT cord-014597-66vd2mdu 811 23 corresponded correspond VBD cord-014597-66vd2mdu 811 24 to to IN cord-014597-66vd2mdu 811 25 a a DT cord-014597-66vd2mdu 811 26 five five CD cord-014597-66vd2mdu 811 27 to to TO cord-014597-66vd2mdu 811 28 six six CD cord-014597-66vd2mdu 811 29 fold fold JJ cord-014597-66vd2mdu 811 30 improvement improvement NN cord-014597-66vd2mdu 811 31 compared compare VBN cord-014597-66vd2mdu 811 32 to to IN cord-014597-66vd2mdu 811 33 the the DT cord-014597-66vd2mdu 811 34 manufacturers manufacturer NNS cord-014597-66vd2mdu 811 35 ' ' POS cord-014597-66vd2mdu 811 36 conditions condition NNS cord-014597-66vd2mdu 811 37 . . . cord-014597-66vd2mdu 812 1 SDS SDS NNP cord-014597-66vd2mdu 812 2 - - HYPH cord-014597-66vd2mdu 812 3 PAGE PAGE NNP cord-014597-66vd2mdu 812 4 analysis analysis NN cord-014597-66vd2mdu 812 5 and and CC cord-014597-66vd2mdu 812 6 SEC SEC NNP cord-014597-66vd2mdu 812 7 - - HYPH cord-014597-66vd2mdu 812 8 HPLC HPLC NNP cord-014597-66vd2mdu 812 9 showed show VBD cord-014597-66vd2mdu 812 10 that that IN cord-014597-66vd2mdu 812 11 our -PRON- PRP$ cord-014597-66vd2mdu 812 12 elution elution NN cord-014597-66vd2mdu 812 13 strategy strategy NN cord-014597-66vd2mdu 812 14 resulted result VBD cord-014597-66vd2mdu 812 15 in in IN cord-014597-66vd2mdu 812 16 a a DT cord-014597-66vd2mdu 812 17 very very RB cord-014597-66vd2mdu 812 18 pure pure JJ cord-014597-66vd2mdu 812 19 product product NN cord-014597-66vd2mdu 812 20 after after IN cord-014597-66vd2mdu 812 21 a a DT cord-014597-66vd2mdu 812 22 single single JJ cord-014597-66vd2mdu 812 23 chromatographic chromatographic JJ cord-014597-66vd2mdu 812 24 step step NN cord-014597-66vd2mdu 812 25 . . . cord-014597-66vd2mdu 813 1 The the DT cord-014597-66vd2mdu 813 2 purification purification NN cord-014597-66vd2mdu 813 3 strategy strategy NN cord-014597-66vd2mdu 813 4 was be VBD cord-014597-66vd2mdu 813 5 verified verify VBN cord-014597-66vd2mdu 813 6 with with IN cord-014597-66vd2mdu 813 7 the the DT cord-014597-66vd2mdu 813 8 IgM103 IgM103 NNP cord-014597-66vd2mdu 813 9 , , , cord-014597-66vd2mdu 813 10 IgM104 IgM104 NNP cord-014597-66vd2mdu 813 11 and and CC cord-014597-66vd2mdu 813 12 IgM617 IgM617 NNP cord-014597-66vd2mdu 813 13 . . . cord-014597-66vd2mdu 814 1 Our -PRON- PRP$ cord-014597-66vd2mdu 814 2 model model NN cord-014597-66vd2mdu 814 3 IgMs IgMs NNP cord-014597-66vd2mdu 814 4 were be VBD cord-014597-66vd2mdu 814 5 produced produce VBN cord-014597-66vd2mdu 814 6 in in IN cord-014597-66vd2mdu 814 7 a a DT cord-014597-66vd2mdu 814 8 ratio ratio NN cord-014597-66vd2mdu 814 9 of of IN cord-014597-66vd2mdu 814 10 approximately approximately RB cord-014597-66vd2mdu 814 11 4:1 4:1 CD cord-014597-66vd2mdu 814 12 pentameric pentameric NN cord-014597-66vd2mdu 814 13 to to IN cord-014597-66vd2mdu 814 14 dimeric dimeric JJ cord-014597-66vd2mdu 814 15 IgM IgM NNP cord-014597-66vd2mdu 814 16 , , , cord-014597-66vd2mdu 814 17 measured measure VBN cord-014597-66vd2mdu 814 18 concordantly concordantly RB cord-014597-66vd2mdu 814 19 with with IN cord-014597-66vd2mdu 814 20 both both DT cord-014597-66vd2mdu 814 21 analytical analytical JJ cord-014597-66vd2mdu 814 22 methods method NNS cord-014597-66vd2mdu 814 23 . . . cord-014597-66vd2mdu 815 1 Process process NN cord-014597-66vd2mdu 815 2 development development NN cord-014597-66vd2mdu 815 3 on on IN cord-014597-66vd2mdu 815 4 IgM IgM NNP cord-014597-66vd2mdu 815 5 purification purification NN cord-014597-66vd2mdu 815 6 using use VBG cord-014597-66vd2mdu 815 7 the the DT cord-014597-66vd2mdu 815 8 POROS POROS NNP cord-014597-66vd2mdu 815 9 Capture Capture NNP cord-014597-66vd2mdu 815 10 Select Select NNP cord-014597-66vd2mdu 815 11 human human JJ cord-014597-66vd2mdu 815 12 IgM IgM NNP cord-014597-66vd2mdu 815 13 affinity affinity NNP cord-014597-66vd2mdu 815 14 matrix matrix NNP cord-014597-66vd2mdu 815 15 enabled enable VBD cord-014597-66vd2mdu 815 16 the the DT cord-014597-66vd2mdu 815 17 recovery recovery NN cord-014597-66vd2mdu 815 18 of of IN cord-014597-66vd2mdu 815 19 highly highly RB cord-014597-66vd2mdu 815 20 pure pure JJ cord-014597-66vd2mdu 815 21 fractions fraction NNS cord-014597-66vd2mdu 815 22 . . . cord-014597-66vd2mdu 816 1 Through through IN cord-014597-66vd2mdu 816 2 optimization optimization NN cord-014597-66vd2mdu 816 3 , , , cord-014597-66vd2mdu 816 4 by by IN cord-014597-66vd2mdu 816 5 combining combine VBG cord-014597-66vd2mdu 816 6 mild mild JJ cord-014597-66vd2mdu 816 7 pH ph NN cord-014597-66vd2mdu 816 8 and and CC cord-014597-66vd2mdu 816 9 high high JJ cord-014597-66vd2mdu 816 10 salt salt NN cord-014597-66vd2mdu 816 11 concentrations concentration NNS cord-014597-66vd2mdu 816 12 , , , cord-014597-66vd2mdu 816 13 the the DT cord-014597-66vd2mdu 816 14 relatively relatively RB cord-014597-66vd2mdu 816 15 low low JJ cord-014597-66vd2mdu 816 16 elution elution NN cord-014597-66vd2mdu 816 17 yields yield NNS cord-014597-66vd2mdu 816 18 were be VBD cord-014597-66vd2mdu 816 19 increased increase VBN cord-014597-66vd2mdu 816 20 by by IN cord-014597-66vd2mdu 816 21 a a DT cord-014597-66vd2mdu 816 22 factor factor NN cord-014597-66vd2mdu 816 23 of of IN cord-014597-66vd2mdu 816 24 5 5 CD cord-014597-66vd2mdu 816 25 - - SYM cord-014597-66vd2mdu 816 26 6 6 CD cord-014597-66vd2mdu 816 27 . . . cord-014597-66vd2mdu 817 1 Applying apply VBG cord-014597-66vd2mdu 817 2 densitometry densitometry NN cord-014597-66vd2mdu 817 3 and and CC cord-014597-66vd2mdu 817 4 SEC SEC NNP cord-014597-66vd2mdu 817 5 - - HYPH cord-014597-66vd2mdu 817 6 HPLC HPLC NNP cord-014597-66vd2mdu 818 1 we -PRON- PRP cord-014597-66vd2mdu 818 2 will will MD cord-014597-66vd2mdu 818 3 investigate investigate VB cord-014597-66vd2mdu 818 4 how how WRB cord-014597-66vd2mdu 818 5 culture culture NN cord-014597-66vd2mdu 818 6 conditions condition NNS cord-014597-66vd2mdu 818 7 influence influence VBP cord-014597-66vd2mdu 818 8 polymer polymer NN cord-014597-66vd2mdu 818 9 formation formation NN cord-014597-66vd2mdu 818 10 in in IN cord-014597-66vd2mdu 818 11 future future NN cord-014597-66vd2mdu 818 12 . . . cord-014597-66vd2mdu 819 1 Currently currently RB cord-014597-66vd2mdu 819 2 , , , cord-014597-66vd2mdu 819 3 no no DT cord-014597-66vd2mdu 819 4 small small JJ cord-014597-66vd2mdu 819 5 scale scale NN cord-014597-66vd2mdu 819 6 ( ( -LRB- cord-014597-66vd2mdu 819 7 < < XX cord-014597-66vd2mdu 819 8 0.5L 0.5L NNS cord-014597-66vd2mdu 819 9 ) ) -RRB- cord-014597-66vd2mdu 820 1 cell cell NN cord-014597-66vd2mdu 820 2 culture culture NN cord-014597-66vd2mdu 820 3 system system NN cord-014597-66vd2mdu 820 4 is be VBZ cord-014597-66vd2mdu 820 5 commercially commercially RB cord-014597-66vd2mdu 820 6 available available JJ cord-014597-66vd2mdu 820 7 for for IN cord-014597-66vd2mdu 820 8 high high JJ cord-014597-66vd2mdu 820 9 cell cell NN cord-014597-66vd2mdu 820 10 density density NN cord-014597-66vd2mdu 820 11 perfusion perfusion NN cord-014597-66vd2mdu 820 12 cultivations cultivation NNS cord-014597-66vd2mdu 820 13 to to TO cord-014597-66vd2mdu 820 14 use use VB cord-014597-66vd2mdu 820 15 in in IN cord-014597-66vd2mdu 820 16 high high JJ cord-014597-66vd2mdu 820 17 throughput throughput NN cord-014597-66vd2mdu 820 18 screening screening NN cord-014597-66vd2mdu 820 19 studies study NNS cord-014597-66vd2mdu 820 20 . . . cord-014597-66vd2mdu 821 1 To to TO cord-014597-66vd2mdu 821 2 increase increase VB cord-014597-66vd2mdu 821 3 throughput throughput NN cord-014597-66vd2mdu 821 4 for for IN cord-014597-66vd2mdu 821 5 process process NN cord-014597-66vd2mdu 821 6 characterization characterization NN cord-014597-66vd2mdu 821 7 activities activity NNS cord-014597-66vd2mdu 821 8 at at IN cord-014597-66vd2mdu 821 9 Janssen Janssen NNP cord-014597-66vd2mdu 821 10 Vaccines Vaccines NNP cord-014597-66vd2mdu 821 11 and and CC cord-014597-66vd2mdu 821 12 Prevention Prevention NNP cord-014597-66vd2mdu 821 13 , , , cord-014597-66vd2mdu 821 14 a a DT cord-014597-66vd2mdu 821 15 shaker shaker NN cord-014597-66vd2mdu 821 16 flask flask NN cord-014597-66vd2mdu 821 17 - - HYPH cord-014597-66vd2mdu 821 18 based base VBN cord-014597-66vd2mdu 821 19 scale scale NN cord-014597-66vd2mdu 821 20 down down RP cord-014597-66vd2mdu 821 21 model model NN cord-014597-66vd2mdu 821 22 was be VBD cord-014597-66vd2mdu 821 23 developed develop VBN cord-014597-66vd2mdu 821 24 . . . cord-014597-66vd2mdu 822 1 Though though RB cord-014597-66vd2mdu 822 2 , , , cord-014597-66vd2mdu 822 3 the the DT cord-014597-66vd2mdu 822 4 control control NN cord-014597-66vd2mdu 822 5 possibilities possibility NNS cord-014597-66vd2mdu 822 6 of of IN cord-014597-66vd2mdu 822 7 shaker shaker NN cord-014597-66vd2mdu 822 8 flask flask NN cord-014597-66vd2mdu 822 9 cultures culture NNS cord-014597-66vd2mdu 822 10 are be VBP cord-014597-66vd2mdu 822 11 technically technically RB cord-014597-66vd2mdu 822 12 very very RB cord-014597-66vd2mdu 822 13 limited limited JJ cord-014597-66vd2mdu 822 14 and and CC cord-014597-66vd2mdu 822 15 different different JJ cord-014597-66vd2mdu 822 16 compared compare VBN cord-014597-66vd2mdu 822 17 to to IN cord-014597-66vd2mdu 822 18 a a DT cord-014597-66vd2mdu 822 19 bioreactor bioreactor NN cord-014597-66vd2mdu 822 20 controlled control VBN cord-014597-66vd2mdu 822 21 process process NN cord-014597-66vd2mdu 822 22 . . . cord-014597-66vd2mdu 823 1 In in IN cord-014597-66vd2mdu 823 2 addition addition NN cord-014597-66vd2mdu 823 3 , , , cord-014597-66vd2mdu 823 4 the the DT cord-014597-66vd2mdu 823 5 sensitivity sensitivity NN cord-014597-66vd2mdu 823 6 of of IN cord-014597-66vd2mdu 823 7 the the DT cord-014597-66vd2mdu 823 8 shaker shaker NN cord-014597-66vd2mdu 823 9 flask flask NN cord-014597-66vd2mdu 823 10 model model NN cord-014597-66vd2mdu 823 11 should should MD cord-014597-66vd2mdu 823 12 allow allow VB cord-014597-66vd2mdu 823 13 the the DT cord-014597-66vd2mdu 823 14 detection detection NN cord-014597-66vd2mdu 823 15 of of IN cord-014597-66vd2mdu 823 16 the the DT cord-014597-66vd2mdu 823 17 effects effect NNS cord-014597-66vd2mdu 823 18 of of IN cord-014597-66vd2mdu 823 19 process process NN cord-014597-66vd2mdu 823 20 parameters parameter NNS cord-014597-66vd2mdu 823 21 on on IN cord-014597-66vd2mdu 823 22 critical critical JJ cord-014597-66vd2mdu 823 23 quality quality NN cord-014597-66vd2mdu 823 24 attributes attribute NNS cord-014597-66vd2mdu 823 25 ( ( -LRB- cord-014597-66vd2mdu 823 26 CQAs CQAs NNP cord-014597-66vd2mdu 823 27 ) ) -RRB- cord-014597-66vd2mdu 823 28 of of IN cord-014597-66vd2mdu 823 29 the the DT cord-014597-66vd2mdu 823 30 vaccine vaccine NN cord-014597-66vd2mdu 823 31 produced produce VBN cord-014597-66vd2mdu 823 32 at at IN cord-014597-66vd2mdu 823 33 large large JJ cord-014597-66vd2mdu 823 34 scale scale NN cord-014597-66vd2mdu 823 35 . . . cord-014597-66vd2mdu 824 1 Iterative iterative JJ cord-014597-66vd2mdu 824 2 experiments experiment NNS cord-014597-66vd2mdu 824 3 were be VBD cord-014597-66vd2mdu 824 4 performed perform VBN cord-014597-66vd2mdu 824 5 in in IN cord-014597-66vd2mdu 824 6 shake shake NN cord-014597-66vd2mdu 824 7 flasks flask NNS cord-014597-66vd2mdu 824 8 to to TO cord-014597-66vd2mdu 824 9 evaluate evaluate VB cord-014597-66vd2mdu 824 10 the the DT cord-014597-66vd2mdu 824 11 influence influence NN cord-014597-66vd2mdu 824 12 of of IN cord-014597-66vd2mdu 824 13 cultivation cultivation NN cord-014597-66vd2mdu 824 14 parameters parameter NNS cord-014597-66vd2mdu 824 15 such such JJ cord-014597-66vd2mdu 824 16 as as IN cord-014597-66vd2mdu 824 17 shaking shake VBG cord-014597-66vd2mdu 824 18 speed speed NN cord-014597-66vd2mdu 824 19 , , , cord-014597-66vd2mdu 824 20 working working NN cord-014597-66vd2mdu 824 21 volume volume NN cord-014597-66vd2mdu 824 22 , , , cord-014597-66vd2mdu 824 23 CO2 CO2 NNP cord-014597-66vd2mdu 824 24 % % NN cord-014597-66vd2mdu 824 25 in in IN cord-014597-66vd2mdu 824 26 the the DT cord-014597-66vd2mdu 824 27 incubator incubator NN cord-014597-66vd2mdu 824 28 and and CC cord-014597-66vd2mdu 824 29 daily daily JJ cord-014597-66vd2mdu 824 30 base base NN cord-014597-66vd2mdu 824 31 additions addition NNS cord-014597-66vd2mdu 824 32 on on IN cord-014597-66vd2mdu 824 33 cultivation cultivation NN cord-014597-66vd2mdu 824 34 parameters parameter NNS cord-014597-66vd2mdu 824 35 ( ( -LRB- cord-014597-66vd2mdu 824 36 as as IN cord-014597-66vd2mdu 824 37 cell cell NN cord-014597-66vd2mdu 824 38 growth growth NN cord-014597-66vd2mdu 824 39 , , , cord-014597-66vd2mdu 824 40 pH ph NN cord-014597-66vd2mdu 824 41 and and CC cord-014597-66vd2mdu 824 42 DO DO NNP cord-014597-66vd2mdu 824 43 ) ) -RRB- cord-014597-66vd2mdu 824 44 . . . cord-014597-66vd2mdu 825 1 In in IN cord-014597-66vd2mdu 825 2 addition addition NN cord-014597-66vd2mdu 825 3 , , , cord-014597-66vd2mdu 825 4 a a DT cord-014597-66vd2mdu 825 5 medium medium JJ cord-014597-66vd2mdu 825 6 exchange exchange NN cord-014597-66vd2mdu 825 7 was be VBD cord-014597-66vd2mdu 825 8 tested test VBN cord-014597-66vd2mdu 825 9 to to TO cord-014597-66vd2mdu 825 10 mimic mimic VB cord-014597-66vd2mdu 825 11 the the DT cord-014597-66vd2mdu 825 12 perfusion perfusion NN cord-014597-66vd2mdu 825 13 mode mode NN cord-014597-66vd2mdu 825 14 used use VBN cord-014597-66vd2mdu 825 15 in in IN cord-014597-66vd2mdu 825 16 the the DT cord-014597-66vd2mdu 825 17 bioreactor bioreactor NN cord-014597-66vd2mdu 825 18 process process NN cord-014597-66vd2mdu 825 19 . . . cord-014597-66vd2mdu 826 1 The the DT cord-014597-66vd2mdu 826 2 PreSens PreSens NNP cord-014597-66vd2mdu 826 3 shake shake NN cord-014597-66vd2mdu 826 4 flask flask NN cord-014597-66vd2mdu 826 5 reader reader NN cord-014597-66vd2mdu 826 6 was be VBD cord-014597-66vd2mdu 826 7 implemented implement VBN cord-014597-66vd2mdu 826 8 to to TO cord-014597-66vd2mdu 826 9 allow allow VB cord-014597-66vd2mdu 826 10 for for IN cord-014597-66vd2mdu 826 11 pH ph NN cord-014597-66vd2mdu 826 12 and and CC cord-014597-66vd2mdu 826 13 DO do VB cord-014597-66vd2mdu 826 14 monitoring monitoring NN cord-014597-66vd2mdu 826 15 . . . cord-014597-66vd2mdu 827 1 The the DT cord-014597-66vd2mdu 827 2 conditions condition NNS cord-014597-66vd2mdu 827 3 for for IN cord-014597-66vd2mdu 827 4 which which WDT cord-014597-66vd2mdu 827 5 the the DT cord-014597-66vd2mdu 827 6 performance performance NN cord-014597-66vd2mdu 827 7 as as IN cord-014597-66vd2mdu 827 8 reflected reflect VBN cord-014597-66vd2mdu 827 9 in in IN cord-014597-66vd2mdu 827 10 specific specific JJ cord-014597-66vd2mdu 827 11 virus virus NN cord-014597-66vd2mdu 827 12 titer titer NN cord-014597-66vd2mdu 827 13 showed show VBD cord-014597-66vd2mdu 827 14 the the DT cord-014597-66vd2mdu 827 15 best good JJS cord-014597-66vd2mdu 827 16 fit fit NN cord-014597-66vd2mdu 827 17 were be VBD cord-014597-66vd2mdu 827 18 selected select VBN cord-014597-66vd2mdu 827 19 . . . cord-014597-66vd2mdu 828 1 At at IN cord-014597-66vd2mdu 828 2 these these DT cord-014597-66vd2mdu 828 3 conditions condition NNS cord-014597-66vd2mdu 828 4 , , , cord-014597-66vd2mdu 828 5 a a DT cord-014597-66vd2mdu 828 6 series series NN cord-014597-66vd2mdu 828 7 of of IN cord-014597-66vd2mdu 828 8 parallel parallel JJ cord-014597-66vd2mdu 828 9 shaker shaker NN cord-014597-66vd2mdu 828 10 flask flask NN cord-014597-66vd2mdu 828 11 infections infection NNS cord-014597-66vd2mdu 828 12 were be VBD cord-014597-66vd2mdu 828 13 conducted conduct VBN cord-014597-66vd2mdu 828 14 to to TO cord-014597-66vd2mdu 828 15 demonstrate demonstrate VB cord-014597-66vd2mdu 828 16 statistical statistical JJ cord-014597-66vd2mdu 828 17 equivalence equivalence NN cord-014597-66vd2mdu 828 18 of of IN cord-014597-66vd2mdu 828 19 performance performance NN cord-014597-66vd2mdu 828 20 parameter parameter NN cord-014597-66vd2mdu 828 21 and and CC cord-014597-66vd2mdu 828 22 CQAs cqa NNS cord-014597-66vd2mdu 828 23 ( ( -LRB- cord-014597-66vd2mdu 828 24 as as IN cord-014597-66vd2mdu 828 25 cell cell NN cord-014597-66vd2mdu 828 26 specific specific JJ cord-014597-66vd2mdu 828 27 IU IU NNP cord-014597-66vd2mdu 828 28 titer titer NN cord-014597-66vd2mdu 828 29 and and CC cord-014597-66vd2mdu 828 30 VP VP NNP cord-014597-66vd2mdu 828 31 / / SYM cord-014597-66vd2mdu 828 32 IU IU NNP cord-014597-66vd2mdu 828 33 ratio ratio NN cord-014597-66vd2mdu 828 34 ) ) -RRB- cord-014597-66vd2mdu 828 35 between between IN cord-014597-66vd2mdu 828 36 the the DT cord-014597-66vd2mdu 828 37 production production NN cord-014597-66vd2mdu 828 38 scale scale NN cord-014597-66vd2mdu 828 39 and and CC cord-014597-66vd2mdu 828 40 reduced reduce VBN cord-014597-66vd2mdu 828 41 scale scale NN cord-014597-66vd2mdu 828 42 processes process NNS cord-014597-66vd2mdu 828 43 and and CC cord-014597-66vd2mdu 828 44 thus thus RB cord-014597-66vd2mdu 828 45 to to TO cord-014597-66vd2mdu 828 46 qualify qualify VB cord-014597-66vd2mdu 828 47 the the DT cord-014597-66vd2mdu 828 48 shake shake NN cord-014597-66vd2mdu 828 49 flask flask NN cord-014597-66vd2mdu 828 50 as as IN cord-014597-66vd2mdu 828 51 a a DT cord-014597-66vd2mdu 828 52 scale scale NN cord-014597-66vd2mdu 828 53 - - HYPH cord-014597-66vd2mdu 828 54 down down RP cord-014597-66vd2mdu 828 55 model model NN cord-014597-66vd2mdu 828 56 . . . cord-014597-66vd2mdu 829 1 A a DT cord-014597-66vd2mdu 829 2 daily daily JJ cord-014597-66vd2mdu 829 3 medium medium JJ cord-014597-66vd2mdu 829 4 exchange exchange NN cord-014597-66vd2mdu 829 5 by by IN cord-014597-66vd2mdu 829 6 centrifugation centrifugation NN cord-014597-66vd2mdu 829 7 was be VBD cord-014597-66vd2mdu 829 8 implemented implement VBN cord-014597-66vd2mdu 829 9 and and CC cord-014597-66vd2mdu 829 10 cultivation cultivation NN cord-014597-66vd2mdu 829 11 parameters parameter NNS cord-014597-66vd2mdu 829 12 for for IN cord-014597-66vd2mdu 829 13 shake shake NN cord-014597-66vd2mdu 829 14 flasks flask NNS cord-014597-66vd2mdu 829 15 were be VBD cord-014597-66vd2mdu 829 16 identified identify VBN cord-014597-66vd2mdu 829 17 . . . cord-014597-66vd2mdu 830 1 Based base VBN cord-014597-66vd2mdu 830 2 on on IN cord-014597-66vd2mdu 830 3 performance performance NN cord-014597-66vd2mdu 830 4 parameter parameter NN cord-014597-66vd2mdu 830 5 ( ( -LRB- cord-014597-66vd2mdu 830 6 cell cell NN cord-014597-66vd2mdu 830 7 specific specific JJ cord-014597-66vd2mdu 830 8 VP VP NNP cord-014597-66vd2mdu 830 9 titer titer NN cord-014597-66vd2mdu 830 10 ) ) -RRB- cord-014597-66vd2mdu 830 11 and and CC cord-014597-66vd2mdu 830 12 the the DT cord-014597-66vd2mdu 830 13 CQAs cqa NNS cord-014597-66vd2mdu 830 14 of of IN cord-014597-66vd2mdu 830 15 the the DT cord-014597-66vd2mdu 830 16 vaccine vaccine NN cord-014597-66vd2mdu 830 17 ( ( -LRB- cord-014597-66vd2mdu 830 18 cell cell NN cord-014597-66vd2mdu 830 19 specific specific JJ cord-014597-66vd2mdu 830 20 IU IU NNP cord-014597-66vd2mdu 830 21 titer titer NN cord-014597-66vd2mdu 830 22 and and CC cord-014597-66vd2mdu 830 23 VP VP NNP cord-014597-66vd2mdu 830 24 / / SYM cord-014597-66vd2mdu 830 25 IU IU NNP cord-014597-66vd2mdu 830 26 ratio ratio NN cord-014597-66vd2mdu 830 27 ) ) -RRB- cord-014597-66vd2mdu 830 28 , , , cord-014597-66vd2mdu 830 29 equivalence equivalence NN cord-014597-66vd2mdu 830 30 between between IN cord-014597-66vd2mdu 830 31 the the DT cord-014597-66vd2mdu 830 32 production production NN cord-014597-66vd2mdu 830 33 - - HYPH cord-014597-66vd2mdu 830 34 scale scale NN cord-014597-66vd2mdu 830 35 and and CC cord-014597-66vd2mdu 830 36 scale scale VB cord-014597-66vd2mdu 830 37 down down RP cord-014597-66vd2mdu 830 38 systems system NNS cord-014597-66vd2mdu 830 39 was be VBD cord-014597-66vd2mdu 830 40 confirmed confirm VBN cord-014597-66vd2mdu 830 41 . . . cord-014597-66vd2mdu 831 1 The the DT cord-014597-66vd2mdu 831 2 scale scale NN cord-014597-66vd2mdu 831 3 down down RP cord-014597-66vd2mdu 831 4 model model NN cord-014597-66vd2mdu 831 5 data datum NNS cord-014597-66vd2mdu 831 6 fall fall NN cord-014597-66vd2mdu 831 7 into into IN cord-014597-66vd2mdu 831 8 the the DT cord-014597-66vd2mdu 831 9 95 95 CD cord-014597-66vd2mdu 831 10 % % NN cord-014597-66vd2mdu 831 11 prediction prediction NN cord-014597-66vd2mdu 831 12 intervals interval NNS cord-014597-66vd2mdu 831 13 calculated calculate VBN cord-014597-66vd2mdu 831 14 on on IN cord-014597-66vd2mdu 831 15 manufacturing manufacture VBG cord-014597-66vd2mdu 831 16 data datum NNS cord-014597-66vd2mdu 831 17 whereas whereas IN cord-014597-66vd2mdu 831 18 scale scale VBP cord-014597-66vd2mdu 831 19 down down RP cord-014597-66vd2mdu 831 20 model model NN cord-014597-66vd2mdu 831 21 data datum NNS cord-014597-66vd2mdu 831 22 from from IN cord-014597-66vd2mdu 831 23 batch batch NN cord-014597-66vd2mdu 831 24 mode mode NN cord-014597-66vd2mdu 831 25 experiments experiment NNS cord-014597-66vd2mdu 831 26 ( ( -LRB- cord-014597-66vd2mdu 831 27 using use VBG cord-014597-66vd2mdu 831 28 non non JJ cord-014597-66vd2mdu 831 29 optimized optimized JJ cord-014597-66vd2mdu 831 30 cultivation cultivation NN cord-014597-66vd2mdu 831 31 conditions condition NNS cord-014597-66vd2mdu 831 32 ) ) -RRB- cord-014597-66vd2mdu 831 33 do do VBP cord-014597-66vd2mdu 831 34 not not RB cord-014597-66vd2mdu 831 35 . . . cord-014597-66vd2mdu 832 1 The the DT cord-014597-66vd2mdu 832 2 shaker shaker NN cord-014597-66vd2mdu 832 3 flask flask NN cord-014597-66vd2mdu 832 4 as as IN cord-014597-66vd2mdu 832 5 a a DT cord-014597-66vd2mdu 832 6 scale scale NN cord-014597-66vd2mdu 832 7 down down RP cord-014597-66vd2mdu 832 8 model model NN cord-014597-66vd2mdu 832 9 for for IN cord-014597-66vd2mdu 832 10 the the DT cord-014597-66vd2mdu 832 11 10L 10l JJ cord-014597-66vd2mdu 832 12 bioreactor bioreactor NN cord-014597-66vd2mdu 832 13 perfusion perfusion NN cord-014597-66vd2mdu 832 14 process process NN cord-014597-66vd2mdu 832 15 was be VBD cord-014597-66vd2mdu 832 16 qualified qualified JJ cord-014597-66vd2mdu 832 17 . . . cord-014597-66vd2mdu 833 1 This this DT cord-014597-66vd2mdu 833 2 model model NN cord-014597-66vd2mdu 833 3 is be VBZ cord-014597-66vd2mdu 833 4 a a DT cord-014597-66vd2mdu 833 5 tool tool NN cord-014597-66vd2mdu 833 6 to to TO cord-014597-66vd2mdu 833 7 screen screen VB cord-014597-66vd2mdu 833 8 a a DT cord-014597-66vd2mdu 833 9 subset subset NN cord-014597-66vd2mdu 833 10 of of IN cord-014597-66vd2mdu 833 11 process process NN cord-014597-66vd2mdu 833 12 parameters parameter NNS cord-014597-66vd2mdu 833 13 at at IN cord-014597-66vd2mdu 833 14 a a DT cord-014597-66vd2mdu 833 15 higher high JJR cord-014597-66vd2mdu 833 16 throughput throughput NN cord-014597-66vd2mdu 833 17 , , , cord-014597-66vd2mdu 833 18 thereby thereby RB cord-014597-66vd2mdu 833 19 reducing reduce VBG cord-014597-66vd2mdu 833 20 process process NN cord-014597-66vd2mdu 833 21 characterization characterization NN cord-014597-66vd2mdu 833 22 timelines timeline NNS cord-014597-66vd2mdu 833 23 . . . cord-014597-66vd2mdu 834 1 Background background NN cord-014597-66vd2mdu 834 2 Until until IN cord-014597-66vd2mdu 834 3 today today NN cord-014597-66vd2mdu 834 4 , , , cord-014597-66vd2mdu 834 5 the the DT cord-014597-66vd2mdu 834 6 market market NN cord-014597-66vd2mdu 834 7 for for IN cord-014597-66vd2mdu 834 8 therapeutic therapeutic JJ cord-014597-66vd2mdu 834 9 proteins protein NNS cord-014597-66vd2mdu 834 10 , , , cord-014597-66vd2mdu 834 11 especially especially RB cord-014597-66vd2mdu 834 12 monoclonal monoclonal JJ cord-014597-66vd2mdu 834 13 antibodies antibody NNS cord-014597-66vd2mdu 834 14 , , , cord-014597-66vd2mdu 834 15 is be VBZ cord-014597-66vd2mdu 834 16 gaining gain VBG cord-014597-66vd2mdu 834 17 more more JJR cord-014597-66vd2mdu 834 18 and and CC cord-014597-66vd2mdu 834 19 more more JJR cord-014597-66vd2mdu 834 20 importance importance NN cord-014597-66vd2mdu 834 21 in in IN cord-014597-66vd2mdu 834 22 the the DT cord-014597-66vd2mdu 834 23 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 834 24 field field NN cord-014597-66vd2mdu 834 25 . . . cord-014597-66vd2mdu 835 1 To to TO cord-014597-66vd2mdu 835 2 meet meet VB cord-014597-66vd2mdu 835 3 the the DT cord-014597-66vd2mdu 835 4 increasing increase VBG cord-014597-66vd2mdu 835 5 demand demand NN cord-014597-66vd2mdu 835 6 for for IN cord-014597-66vd2mdu 835 7 these these DT cord-014597-66vd2mdu 835 8 products product NNS cord-014597-66vd2mdu 835 9 , , , cord-014597-66vd2mdu 835 10 the the DT cord-014597-66vd2mdu 835 11 industry industry NN cord-014597-66vd2mdu 835 12 made make VBD cord-014597-66vd2mdu 835 13 tremendous tremendous JJ cord-014597-66vd2mdu 835 14 efforts effort NNS cord-014597-66vd2mdu 835 15 to to TO cord-014597-66vd2mdu 835 16 generate generate VB cord-014597-66vd2mdu 835 17 highly highly RB cord-014597-66vd2mdu 835 18 efficient efficient JJ cord-014597-66vd2mdu 835 19 production production NN cord-014597-66vd2mdu 835 20 systems system NNS cord-014597-66vd2mdu 835 21 . . . cord-014597-66vd2mdu 836 1 One one CD cord-014597-66vd2mdu 836 2 of of IN cord-014597-66vd2mdu 836 3 the the DT cord-014597-66vd2mdu 836 4 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 836 5 industry industry NN cord-014597-66vd2mdu 836 6 's 's POS cord-014597-66vd2mdu 836 7 research research NN cord-014597-66vd2mdu 836 8 focuses focus VBZ cord-014597-66vd2mdu 836 9 is be VBZ cord-014597-66vd2mdu 836 10 the the DT cord-014597-66vd2mdu 836 11 improvement improvement NN cord-014597-66vd2mdu 836 12 of of IN cord-014597-66vd2mdu 836 13 the the DT cord-014597-66vd2mdu 836 14 secretion secretion NN cord-014597-66vd2mdu 836 15 process process NN cord-014597-66vd2mdu 836 16 in in IN cord-014597-66vd2mdu 836 17 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 836 18 cells cell NNS cord-014597-66vd2mdu 836 19 . . . cord-014597-66vd2mdu 837 1 In in IN cord-014597-66vd2mdu 837 2 mammalian mammalian JJ cord-014597-66vd2mdu 837 3 cells cell NNS cord-014597-66vd2mdu 837 4 , , , cord-014597-66vd2mdu 837 5 the the DT cord-014597-66vd2mdu 837 6 efficiency efficiency NN cord-014597-66vd2mdu 837 7 of of IN cord-014597-66vd2mdu 837 8 protein protein NN cord-014597-66vd2mdu 837 9 transportation transportation NN cord-014597-66vd2mdu 837 10 strongly strongly RB cord-014597-66vd2mdu 837 11 depends depend VBZ cord-014597-66vd2mdu 837 12 on on IN cord-014597-66vd2mdu 837 13 the the DT cord-014597-66vd2mdu 837 14 translocation translocation NN cord-014597-66vd2mdu 837 15 of of IN cord-014597-66vd2mdu 837 16 a a DT cord-014597-66vd2mdu 837 17 nascent nascent JJ cord-014597-66vd2mdu 837 18 protein protein NN cord-014597-66vd2mdu 837 19 into into IN cord-014597-66vd2mdu 837 20 the the DT cord-014597-66vd2mdu 837 21 ER er NN cord-014597-66vd2mdu 837 22 , , , cord-014597-66vd2mdu 837 23 which which WDT cord-014597-66vd2mdu 837 24 is be VBZ cord-014597-66vd2mdu 837 25 mostly mostly RB cord-014597-66vd2mdu 837 26 conducted conduct VBN cord-014597-66vd2mdu 837 27 by by IN cord-014597-66vd2mdu 837 28 the the DT cord-014597-66vd2mdu 837 29 signal signal NN cord-014597-66vd2mdu 837 30 peptide peptide NN cord-014597-66vd2mdu 837 31 ( ( -LRB- cord-014597-66vd2mdu 837 32 SP SP NNP cord-014597-66vd2mdu 837 33 ) ) -RRB- cord-014597-66vd2mdu 837 34 coupled couple VBN cord-014597-66vd2mdu 837 35 to to IN cord-014597-66vd2mdu 837 36 the the DT cord-014597-66vd2mdu 837 37 Nterminus Nterminus NNP cord-014597-66vd2mdu 837 38 . . . cord-014597-66vd2mdu 838 1 Through through IN cord-014597-66vd2mdu 838 2 the the DT cord-014597-66vd2mdu 838 3 interchangeability interchangeability NN cord-014597-66vd2mdu 838 4 of of IN cord-014597-66vd2mdu 838 5 signal signal NN cord-014597-66vd2mdu 838 6 peptides peptide NNS cord-014597-66vd2mdu 838 7 between between IN cord-014597-66vd2mdu 838 8 products product NNS cord-014597-66vd2mdu 838 9 and and CC cord-014597-66vd2mdu 838 10 even even RB cord-014597-66vd2mdu 838 11 species specie NNS cord-014597-66vd2mdu 838 12 , , , cord-014597-66vd2mdu 838 13 a a DT cord-014597-66vd2mdu 838 14 large large JJ cord-014597-66vd2mdu 838 15 variety variety NN cord-014597-66vd2mdu 838 16 can can MD cord-014597-66vd2mdu 838 17 be be VB cord-014597-66vd2mdu 838 18 used use VBN cord-014597-66vd2mdu 838 19 to to TO cord-014597-66vd2mdu 838 20 enhance enhance VB cord-014597-66vd2mdu 838 21 protein protein NN cord-014597-66vd2mdu 838 22 expression expression NN cord-014597-66vd2mdu 838 23 in in IN cord-014597-66vd2mdu 838 24 already already RB cord-014597-66vd2mdu 838 25 existing exist VBG cord-014597-66vd2mdu 838 26 production production NN cord-014597-66vd2mdu 838 27 systems system NNS cord-014597-66vd2mdu 838 28 Materials material NNS cord-014597-66vd2mdu 838 29 and and CC cord-014597-66vd2mdu 838 30 methods method NNS cord-014597-66vd2mdu 838 31 At at IN cord-014597-66vd2mdu 838 32 first first RB cord-014597-66vd2mdu 838 33 the the DT cord-014597-66vd2mdu 838 34 influence influence NN cord-014597-66vd2mdu 838 35 of of IN cord-014597-66vd2mdu 838 36 four four CD cord-014597-66vd2mdu 838 37 different different JJ cord-014597-66vd2mdu 838 38 natural natural JJ cord-014597-66vd2mdu 838 39 SPs sp NNS cord-014597-66vd2mdu 838 40 ( ( -LRB- cord-014597-66vd2mdu 838 41 SP SP NNP cord-014597-66vd2mdu 838 42 ( ( -LRB- cord-014597-66vd2mdu 838 43 7 7 CD cord-014597-66vd2mdu 838 44 ) ) -RRB- cord-014597-66vd2mdu 838 45 , , , cord-014597-66vd2mdu 838 46 ( ( -LRB- cord-014597-66vd2mdu 838 47 8) 8) NNP cord-014597-66vd2mdu 838 48 , , , cord-014597-66vd2mdu 838 49 ( ( -LRB- cord-014597-66vd2mdu 838 50 9 9 CD cord-014597-66vd2mdu 838 51 ) ) -RRB- cord-014597-66vd2mdu 838 52 and and CC cord-014597-66vd2mdu 838 53 ( ( -LRB- cord-014597-66vd2mdu 838 54 10 10 CD cord-014597-66vd2mdu 838 55 ) ) -RRB- cord-014597-66vd2mdu 838 56 ) ) -RRB- cord-014597-66vd2mdu 838 57 was be VBD cord-014597-66vd2mdu 838 58 compared compare VBN cord-014597-66vd2mdu 838 59 on on IN cord-014597-66vd2mdu 838 60 the the DT cord-014597-66vd2mdu 838 61 secreted secrete VBN cord-014597-66vd2mdu 838 62 amount amount NN cord-014597-66vd2mdu 838 63 of of IN cord-014597-66vd2mdu 838 64 an an DT cord-014597-66vd2mdu 838 65 IgG4 igg4 JJ cord-014597-66vd2mdu 838 66 model model NN cord-014597-66vd2mdu 838 67 antibody antibody NN cord-014597-66vd2mdu 838 68 ( ( -LRB- cord-014597-66vd2mdu 838 69 product product NN cord-014597-66vd2mdu 838 70 A a NN cord-014597-66vd2mdu 838 71 ) ) -RRB- cord-014597-66vd2mdu 838 72 in in IN cord-014597-66vd2mdu 838 73 fed fed NNP cord-014597-66vd2mdu 838 74 batches batch NNS cord-014597-66vd2mdu 838 75 using use VBG cord-014597-66vd2mdu 838 76 a a DT cord-014597-66vd2mdu 838 77 CHO CHO NNP cord-014597-66vd2mdu 838 78 DG44 DG44 NNP cord-014597-66vd2mdu 838 79 host host NN cord-014597-66vd2mdu 838 80 cell cell NN cord-014597-66vd2mdu 838 81 line line NN cord-014597-66vd2mdu 838 82 . . . cord-014597-66vd2mdu 839 1 In in IN cord-014597-66vd2mdu 839 2 the the DT cord-014597-66vd2mdu 839 3 second second JJ cord-014597-66vd2mdu 839 4 part part NN cord-014597-66vd2mdu 839 5 , , , cord-014597-66vd2mdu 839 6 one one CD cord-014597-66vd2mdu 839 7 promising promising JJ cord-014597-66vd2mdu 839 8 SP sp NN cord-014597-66vd2mdu 839 9 - - HYPH cord-014597-66vd2mdu 839 10 candidate candidate NN cord-014597-66vd2mdu 839 11 showing show VBG cord-014597-66vd2mdu 839 12 improved improve VBN cord-014597-66vd2mdu 839 13 secretion secretion NN cord-014597-66vd2mdu 839 14 ( ( -LRB- cord-014597-66vd2mdu 839 15 SP SP NNP cord-014597-66vd2mdu 839 16 ( ( -LRB- cord-014597-66vd2mdu 839 17 9 9 CD cord-014597-66vd2mdu 839 18 ) ) -RRB- cord-014597-66vd2mdu 839 19 ) ) -RRB- cord-014597-66vd2mdu 839 20 was be VBD cord-014597-66vd2mdu 839 21 identified identify VBN cord-014597-66vd2mdu 839 22 and and CC cord-014597-66vd2mdu 839 23 the the DT cord-014597-66vd2mdu 839 24 influence influence NN cord-014597-66vd2mdu 839 25 of of IN cord-014597-66vd2mdu 839 26 this this DT cord-014597-66vd2mdu 839 27 SP SP NNP cord-014597-66vd2mdu 839 28 on on IN cord-014597-66vd2mdu 839 29 four four CD cord-014597-66vd2mdu 839 30 additional additional JJ cord-014597-66vd2mdu 839 31 antibody antibody NN cord-014597-66vd2mdu 839 32 products product NNS cord-014597-66vd2mdu 839 33 , , , cord-014597-66vd2mdu 839 34 which which WDT cord-014597-66vd2mdu 839 35 varied vary VBD cord-014597-66vd2mdu 839 36 in in IN cord-014597-66vd2mdu 839 37 their -PRON- PRP$ cord-014597-66vd2mdu 839 38 expressability expressability NN cord-014597-66vd2mdu 839 39 from from IN cord-014597-66vd2mdu 839 40 good good JJ cord-014597-66vd2mdu 839 41 to to IN cord-014597-66vd2mdu 839 42 mid mid NN cord-014597-66vd2mdu 839 43 / / SYM cord-014597-66vd2mdu 839 44 bad bad JJ cord-014597-66vd2mdu 839 45 , , , cord-014597-66vd2mdu 839 46 was be VBD cord-014597-66vd2mdu 839 47 investigated investigate VBN cord-014597-66vd2mdu 839 48 . . . cord-014597-66vd2mdu 840 1 In in IN cord-014597-66vd2mdu 840 2 both both DT cord-014597-66vd2mdu 840 3 approaches approach NNS cord-014597-66vd2mdu 840 4 , , , cord-014597-66vd2mdu 840 5 the the DT cord-014597-66vd2mdu 840 6 standard standard JJ cord-014597-66vd2mdu 840 7 SP SP NNP cord-014597-66vd2mdu 840 8 was be VBD cord-014597-66vd2mdu 840 9 implemented implement VBN cord-014597-66vd2mdu 840 10 for for IN cord-014597-66vd2mdu 840 11 comparative comparative JJ cord-014597-66vd2mdu 840 12 reasons reason NNS cord-014597-66vd2mdu 840 13 . . . cord-014597-66vd2mdu 841 1 In in IN cord-014597-66vd2mdu 841 2 the the DT cord-014597-66vd2mdu 841 3 first first JJ cord-014597-66vd2mdu 841 4 approach approach NN cord-014597-66vd2mdu 841 5 , , , cord-014597-66vd2mdu 841 6 four four CD cord-014597-66vd2mdu 841 7 signal signal NN cord-014597-66vd2mdu 841 8 peptides peptide NNS cord-014597-66vd2mdu 841 9 SP SP NNP cord-014597-66vd2mdu 841 10 ( ( -LRB- cord-014597-66vd2mdu 841 11 7 7 CD cord-014597-66vd2mdu 841 12 ) ) -RRB- cord-014597-66vd2mdu 841 13 , , , cord-014597-66vd2mdu 841 14 SP(8 SP(8 NNP cord-014597-66vd2mdu 841 15 ) ) -RRB- cord-014597-66vd2mdu 841 16 , , , cord-014597-66vd2mdu 841 17 SP(9 SP(9 NNP cord-014597-66vd2mdu 841 18 ) ) -RRB- cord-014597-66vd2mdu 841 19 and and CC cord-014597-66vd2mdu 841 20 SP(10 SP(10 NNP cord-014597-66vd2mdu 841 21 ) ) -RRB- cord-014597-66vd2mdu 841 22 were be VBD cord-014597-66vd2mdu 841 23 screened screen VBN cord-014597-66vd2mdu 841 24 for for IN cord-014597-66vd2mdu 841 25 their -PRON- PRP$ cord-014597-66vd2mdu 841 26 potential potential NN cord-014597-66vd2mdu 841 27 to to TO cord-014597-66vd2mdu 841 28 improve improve VB cord-014597-66vd2mdu 841 29 the the DT cord-014597-66vd2mdu 841 30 product product NN cord-014597-66vd2mdu 841 31 secretion secretion NN cord-014597-66vd2mdu 841 32 of of IN cord-014597-66vd2mdu 841 33 CHO CHO NNP cord-014597-66vd2mdu 841 34 DG44 DG44 NNP cord-014597-66vd2mdu 841 35 cells cell NNS cord-014597-66vd2mdu 841 36 expressing express VBG cord-014597-66vd2mdu 841 37 a a DT cord-014597-66vd2mdu 841 38 model model NN cord-014597-66vd2mdu 841 39 antibody antibody NN cord-014597-66vd2mdu 841 40 ( ( -LRB- cord-014597-66vd2mdu 841 41 product product NN cord-014597-66vd2mdu 841 42 A a NN cord-014597-66vd2mdu 841 43 ) ) -RRB- cord-014597-66vd2mdu 841 44 . . . cord-014597-66vd2mdu 842 1 The the DT cord-014597-66vd2mdu 842 2 results result NNS cord-014597-66vd2mdu 842 3 revealed reveal VBD cord-014597-66vd2mdu 842 4 a a DT cord-014597-66vd2mdu 842 5 2.4-fold 2.4-fold CD cord-014597-66vd2mdu 842 6 increase increase NN cord-014597-66vd2mdu 842 7 in in IN cord-014597-66vd2mdu 842 8 average average JJ cord-014597-66vd2mdu 842 9 final final JJ cord-014597-66vd2mdu 842 10 fed fed NNP cord-014597-66vd2mdu 842 11 - - HYPH cord-014597-66vd2mdu 842 12 batch batch NN cord-014597-66vd2mdu 842 13 antibody antibody NN cord-014597-66vd2mdu 842 14 titer titer NN cord-014597-66vd2mdu 842 15 of of IN cord-014597-66vd2mdu 842 16 SP(9 SP(9 NNP cord-014597-66vd2mdu 842 17 ) ) -RRB- cord-014597-66vd2mdu 842 18 when when WRB cord-014597-66vd2mdu 842 19 compared compare VBN cord-014597-66vd2mdu 842 20 to to IN cord-014597-66vd2mdu 842 21 the the DT cord-014597-66vd2mdu 842 22 standard standard JJ cord-014597-66vd2mdu 842 23 SP SP NNP cord-014597-66vd2mdu 842 24 approach approach NN cord-014597-66vd2mdu 842 25 ( ( -LRB- cord-014597-66vd2mdu 842 26 standard standard JJ cord-014597-66vd2mdu 842 27 SP SP NNP cord-014597-66vd2mdu 842 28 = = SYM cord-014597-66vd2mdu 842 29 0.44 0.44 CD cord-014597-66vd2mdu 842 30 g g NN cord-014597-66vd2mdu 842 31 / / SYM cord-014597-66vd2mdu 842 32 L l NN cord-014597-66vd2mdu 842 33 ; ; : cord-014597-66vd2mdu 842 34 SP(9 SP(9 NNP cord-014597-66vd2mdu 842 35 ) ) -RRB- cord-014597-66vd2mdu 842 36 = = SYM cord-014597-66vd2mdu 842 37 1.50 1.50 CD cord-014597-66vd2mdu 842 38 g g NN cord-014597-66vd2mdu 842 39 / / SYM cord-014597-66vd2mdu 842 40 L L NNP cord-014597-66vd2mdu 842 41 ) ) -RRB- cord-014597-66vd2mdu 842 42 . . . cord-014597-66vd2mdu 843 1 In in IN cord-014597-66vd2mdu 843 2 the the DT cord-014597-66vd2mdu 843 3 second second JJ cord-014597-66vd2mdu 843 4 approach approach NN cord-014597-66vd2mdu 843 5 , , , cord-014597-66vd2mdu 843 6 the the DT cord-014597-66vd2mdu 843 7 enhancing enhance VBG cord-014597-66vd2mdu 843 8 capacity capacity NN cord-014597-66vd2mdu 843 9 of of IN cord-014597-66vd2mdu 843 10 SP(9 sp(9 NN cord-014597-66vd2mdu 843 11 ) ) -RRB- cord-014597-66vd2mdu 843 12 on on IN cord-014597-66vd2mdu 843 13 secretion secretion NN cord-014597-66vd2mdu 843 14 of of IN cord-014597-66vd2mdu 843 15 four four CD cord-014597-66vd2mdu 843 16 other other JJ cord-014597-66vd2mdu 843 17 IgG igg NN cord-014597-66vd2mdu 843 18 products product NNS cord-014597-66vd2mdu 843 19 ( ( -LRB- cord-014597-66vd2mdu 843 20 named name VBN cord-014597-66vd2mdu 843 21 product product NN cord-014597-66vd2mdu 843 22 B b NN cord-014597-66vd2mdu 843 23 to to IN cord-014597-66vd2mdu 843 24 E e NN cord-014597-66vd2mdu 843 25 , , , cord-014597-66vd2mdu 843 26 Table table NN cord-014597-66vd2mdu 843 27 1 1 CD cord-014597-66vd2mdu 843 28 ) ) -RRB- cord-014597-66vd2mdu 843 29 was be VBD cord-014597-66vd2mdu 843 30 further further RB cord-014597-66vd2mdu 843 31 evaluated evaluate VBN cord-014597-66vd2mdu 843 32 . . . cord-014597-66vd2mdu 844 1 An an DT cord-014597-66vd2mdu 844 2 improved improved JJ cord-014597-66vd2mdu 844 3 performance performance NN cord-014597-66vd2mdu 844 4 was be VBD cord-014597-66vd2mdu 844 5 observed observe VBN cord-014597-66vd2mdu 844 6 for for IN cord-014597-66vd2mdu 844 7 all all DT cord-014597-66vd2mdu 844 8 products product NNS cord-014597-66vd2mdu 844 9 when when WRB cord-014597-66vd2mdu 844 10 comparing compare VBG cord-014597-66vd2mdu 844 11 SP(9 SP(9 NNP cord-014597-66vd2mdu 844 12 ) ) -RRB- cord-014597-66vd2mdu 844 13 and and CC cord-014597-66vd2mdu 844 14 the the DT cord-014597-66vd2mdu 844 15 standard standard JJ cord-014597-66vd2mdu 844 16 SP SP NNP cord-014597-66vd2mdu 844 17 in in IN cord-014597-66vd2mdu 844 18 a a DT cord-014597-66vd2mdu 844 19 fed fed NNP cord-014597-66vd2mdu 844 20 batch batch NN cord-014597-66vd2mdu 844 21 process process NN cord-014597-66vd2mdu 844 22 ( ( -LRB- cord-014597-66vd2mdu 844 23 Fig fig NN cord-014597-66vd2mdu 844 24 . . . cord-014597-66vd2mdu 844 25 _SP cord-014597-66vd2mdu 845 1 1 1 LS cord-014597-66vd2mdu 845 2 ) ) -RRB- cord-014597-66vd2mdu 845 3 . . . cord-014597-66vd2mdu 846 1 With with IN cord-014597-66vd2mdu 846 2 an an DT cord-014597-66vd2mdu 846 3 increase increase NN cord-014597-66vd2mdu 846 4 in in IN cord-014597-66vd2mdu 846 5 average average JJ cord-014597-66vd2mdu 846 6 final final JJ cord-014597-66vd2mdu 846 7 fed fed NN cord-014597-66vd2mdu 846 8 - - HYPH cord-014597-66vd2mdu 846 9 batch batch NN cord-014597-66vd2mdu 846 10 titers titer NNS cord-014597-66vd2mdu 846 11 ranging range VBG cord-014597-66vd2mdu 846 12 from from IN cord-014597-66vd2mdu 846 13 28 28 CD cord-014597-66vd2mdu 846 14 to to IN cord-014597-66vd2mdu 846 15 354 354 CD cord-014597-66vd2mdu 846 16 % % NN cord-014597-66vd2mdu 846 17 and and CC cord-014597-66vd2mdu 846 18 up up IN cord-014597-66vd2mdu 846 19 to to TO cord-014597-66vd2mdu 846 20 290 290 CD cord-014597-66vd2mdu 846 21 % % NN cord-014597-66vd2mdu 846 22 in in IN cord-014597-66vd2mdu 846 23 cell cell NN cord-014597-66vd2mdu 846 24 - - HYPH cord-014597-66vd2mdu 846 25 specific specific JJ cord-014597-66vd2mdu 846 26 productivities productivity NNS cord-014597-66vd2mdu 846 27 . . . cord-014597-66vd2mdu 847 1 Taken take VBN cord-014597-66vd2mdu 847 2 together together RB cord-014597-66vd2mdu 847 3 , , , cord-014597-66vd2mdu 847 4 with with IN cord-014597-66vd2mdu 847 5 a a DT cord-014597-66vd2mdu 847 6 positive positive JJ cord-014597-66vd2mdu 847 7 influence influence NN cord-014597-66vd2mdu 847 8 on on IN cord-014597-66vd2mdu 847 9 the the DT cord-014597-66vd2mdu 847 10 final final JJ cord-014597-66vd2mdu 847 11 concentrations concentration NNS cord-014597-66vd2mdu 847 12 of of IN cord-014597-66vd2mdu 847 13 all all DT cord-014597-66vd2mdu 847 14 tested test VBN cord-014597-66vd2mdu 847 15 products product NNS cord-014597-66vd2mdu 847 16 , , , cord-014597-66vd2mdu 847 17 the the DT cord-014597-66vd2mdu 847 18 results result NNS cord-014597-66vd2mdu 847 19 obtained obtain VBN cord-014597-66vd2mdu 847 20 with with IN cord-014597-66vd2mdu 847 21 SP(9 sp(9 NN cord-014597-66vd2mdu 847 22 ) ) -RRB- cord-014597-66vd2mdu 847 23 contribute contribute VB cord-014597-66vd2mdu 847 24 to to IN cord-014597-66vd2mdu 847 25 -Signal -signal JJ cord-014597-66vd2mdu 847 26 peptide peptide NN cord-014597-66vd2mdu 847 27 SP(9 SP(9 NNP cord-014597-66vd2mdu 847 28 ) ) -RRB- cord-014597-66vd2mdu 847 29 was be VBD cord-014597-66vd2mdu 847 30 identified identify VBN cord-014597-66vd2mdu 847 31 as as IN cord-014597-66vd2mdu 847 32 a a DT cord-014597-66vd2mdu 847 33 promising promising JJ cord-014597-66vd2mdu 847 34 candidate candidate NN cord-014597-66vd2mdu 847 35 with with IN cord-014597-66vd2mdu 847 36 an an DT cord-014597-66vd2mdu 847 37 average average JJ cord-014597-66vd2mdu 847 38 2.4-fold 2.4-fold CD cord-014597-66vd2mdu 847 39 titer titer NN cord-014597-66vd2mdu 847 40 increase increase NN cord-014597-66vd2mdu 847 41 during during IN cord-014597-66vd2mdu 847 42 screening screening NN cord-014597-66vd2mdu 847 43 of of IN cord-014597-66vd2mdu 847 44 four four CD cord-014597-66vd2mdu 847 45 signal signal NN cord-014597-66vd2mdu 847 46 peptides peptide NNS cord-014597-66vd2mdu 847 47 . . . cord-014597-66vd2mdu 848 1 -SP(9 -sp(9 LS cord-014597-66vd2mdu 848 2 ) ) -RRB- cord-014597-66vd2mdu 848 3 was be VBD cord-014597-66vd2mdu 848 4 able able JJ cord-014597-66vd2mdu 848 5 to to TO cord-014597-66vd2mdu 848 6 improve improve VB cord-014597-66vd2mdu 848 7 production production NN cord-014597-66vd2mdu 848 8 titers titer NNS cord-014597-66vd2mdu 848 9 up up RP cord-014597-66vd2mdu 848 10 to to IN cord-014597-66vd2mdu 848 11 354 354 CD cord-014597-66vd2mdu 848 12 % % NN cord-014597-66vd2mdu 848 13 compared compare VBN cord-014597-66vd2mdu 848 14 to to IN cord-014597-66vd2mdu 848 15 standard standard JJ cord-014597-66vd2mdu 848 16 SP SP NNP cord-014597-66vd2mdu 848 17 . . . cord-014597-66vd2mdu 849 1 -SP(9 -sp(9 LS cord-014597-66vd2mdu 849 2 ) ) -RRB- cord-014597-66vd2mdu 849 3 was be VBD cord-014597-66vd2mdu 849 4 able able JJ cord-014597-66vd2mdu 849 5 to to TO cord-014597-66vd2mdu 849 6 improve improve VB cord-014597-66vd2mdu 849 7 cell cell NN cord-014597-66vd2mdu 849 8 - - HYPH cord-014597-66vd2mdu 849 9 specific specific JJ cord-014597-66vd2mdu 849 10 productivities productivity NNS cord-014597-66vd2mdu 849 11 up up IN cord-014597-66vd2mdu 849 12 to to TO cord-014597-66vd2mdu 849 13 290 290 CD cord-014597-66vd2mdu 849 14 % % NN cord-014597-66vd2mdu 849 15 compared compare VBN cord-014597-66vd2mdu 849 16 to to IN cord-014597-66vd2mdu 849 17 standard standard JJ cord-014597-66vd2mdu 849 18 SP SP NNP cord-014597-66vd2mdu 849 19 . . . cord-014597-66vd2mdu 850 1 -Future -Future : cord-014597-66vd2mdu 850 2 usage usage NN cord-014597-66vd2mdu 850 3 of of IN cord-014597-66vd2mdu 850 4 SP SP NNP cord-014597-66vd2mdu 850 5 ( ( -LRB- cord-014597-66vd2mdu 850 6 9 9 CD cord-014597-66vd2mdu 850 7 ) ) -RRB- cord-014597-66vd2mdu 850 8 contributes contribute VBZ cord-014597-66vd2mdu 850 9 to to IN cord-014597-66vd2mdu 850 10 the the DT cord-014597-66vd2mdu 850 11 further further JJ cord-014597-66vd2mdu 850 12 optimization optimization NN cord-014597-66vd2mdu 850 13 of of IN cord-014597-66vd2mdu 850 14 Sartorius Sartorius NNP cord-014597-66vd2mdu 850 15 Stedim Stedim NNP cord-014597-66vd2mdu 850 16 Cellca Cellca NNP cord-014597-66vd2mdu 850 17 's 's POS cord-014597-66vd2mdu 850 18 standard standard JJ cord-014597-66vd2mdu 850 19 cell cell NN cord-014597-66vd2mdu 850 20 line line NN cord-014597-66vd2mdu 850 21 development development NN cord-014597-66vd2mdu 850 22 process process NN cord-014597-66vd2mdu 850 23 . . . cord-014597-66vd2mdu 851 1 New new JJ cord-014597-66vd2mdu 851 2 platform platform NN cord-014597-66vd2mdu 851 3 for for IN cord-014597-66vd2mdu 851 4 the the DT cord-014597-66vd2mdu 851 5 integrated integrated JJ cord-014597-66vd2mdu 851 6 analysis analysis NN cord-014597-66vd2mdu 851 7 of of IN cord-014597-66vd2mdu 851 8 bioreactor bioreactor NN cord-014597-66vd2mdu 851 9 online online RB cord-014597-66vd2mdu 851 10 and and CC cord-014597-66vd2mdu 851 11 offline offline JJ cord-014597-66vd2mdu 851 12 data datum NNS cord-014597-66vd2mdu 851 13 Lukasz Lukasz NNP cord-014597-66vd2mdu 851 14 Gricman Gricman NNP cord-014597-66vd2mdu 851 15 1 1 CD cord-014597-66vd2mdu 851 16 , , , cord-014597-66vd2mdu 851 17 Milan Milan NNP cord-014597-66vd2mdu 851 18 Ganguly Ganguly NNP cord-014597-66vd2mdu 851 19 2 2 CD cord-014597-66vd2mdu 851 20 , , , cord-014597-66vd2mdu 851 21 Amanda Amanda NNP cord-014597-66vd2mdu 851 22 Fitzgerald Fitzgerald NNP cord-014597-66vd2mdu 851 23 3 3 CD cord-014597-66vd2mdu 851 24 , , , cord-014597-66vd2mdu 851 25 Hans Hans NNP cord-014597-66vd2mdu 851 26 Peter Peter NNP cord-014597-66vd2mdu 852 1 More More JJR cord-014597-66vd2mdu 852 2 and and CC cord-014597-66vd2mdu 852 3 more more JJR cord-014597-66vd2mdu 852 4 experiments experiment NNS cord-014597-66vd2mdu 852 5 are be VBP cord-014597-66vd2mdu 852 6 used use VBN cord-014597-66vd2mdu 852 7 to to TO cord-014597-66vd2mdu 852 8 assess assess VB cord-014597-66vd2mdu 852 9 bioreactor bioreactor NN cord-014597-66vd2mdu 852 10 suitability suitability NN cord-014597-66vd2mdu 852 11 and and CC cord-014597-66vd2mdu 852 12 stability stability NN cord-014597-66vd2mdu 852 13 of of IN cord-014597-66vd2mdu 852 14 clones clone NNS cord-014597-66vd2mdu 852 15 , , , cord-014597-66vd2mdu 852 16 to to TO cord-014597-66vd2mdu 852 17 evaluate evaluate VB cord-014597-66vd2mdu 852 18 media medium NNS cord-014597-66vd2mdu 852 19 composition composition NN cord-014597-66vd2mdu 852 20 and and CC cord-014597-66vd2mdu 852 21 other other JJ cord-014597-66vd2mdu 852 22 process process NN cord-014597-66vd2mdu 852 23 parameters parameter NNS cord-014597-66vd2mdu 852 24 , , , cord-014597-66vd2mdu 852 25 and and CC cord-014597-66vd2mdu 852 26 to to TO cord-014597-66vd2mdu 852 27 start start VB cord-014597-66vd2mdu 852 28 upscaling upscaling JJ cord-014597-66vd2mdu 852 29 campaigns campaign NNS cord-014597-66vd2mdu 852 30 . . . cord-014597-66vd2mdu 853 1 This this DT cord-014597-66vd2mdu 853 2 has have VBZ cord-014597-66vd2mdu 853 3 resulted result VBN cord-014597-66vd2mdu 853 4 in in IN cord-014597-66vd2mdu 853 5 a a DT cord-014597-66vd2mdu 853 6 major major JJ cord-014597-66vd2mdu 853 7 bottleneck bottleneck NN cord-014597-66vd2mdu 853 8 due due IN cord-014597-66vd2mdu 853 9 to to IN cord-014597-66vd2mdu 853 10 the the DT cord-014597-66vd2mdu 853 11 increase increase NN cord-014597-66vd2mdu 853 12 in in IN cord-014597-66vd2mdu 853 13 data datum NNS cord-014597-66vd2mdu 853 14 capturing capture VBG cord-014597-66vd2mdu 853 15 , , , cord-014597-66vd2mdu 853 16 processing processing NN cord-014597-66vd2mdu 853 17 , , , cord-014597-66vd2mdu 853 18 aggregation aggregation NN cord-014597-66vd2mdu 853 19 , , , cord-014597-66vd2mdu 853 20 visualization visualization NN cord-014597-66vd2mdu 853 21 , , , cord-014597-66vd2mdu 853 22 and and CC cord-014597-66vd2mdu 853 23 statistical statistical JJ cord-014597-66vd2mdu 853 24 analysis analysis NN cord-014597-66vd2mdu 853 25 . . . cord-014597-66vd2mdu 854 1 In in IN cord-014597-66vd2mdu 854 2 addition addition NN cord-014597-66vd2mdu 854 3 , , , cord-014597-66vd2mdu 854 4 the the DT cord-014597-66vd2mdu 854 5 association association NN cord-014597-66vd2mdu 854 6 of of IN cord-014597-66vd2mdu 854 7 the the DT cord-014597-66vd2mdu 854 8 data datum NNS cord-014597-66vd2mdu 854 9 with with IN cord-014597-66vd2mdu 854 10 the the DT cord-014597-66vd2mdu 854 11 experimental experimental JJ cord-014597-66vd2mdu 854 12 context context NN cord-014597-66vd2mdu 854 13 ( ( -LRB- cord-014597-66vd2mdu 854 14 e.g. e.g. RB cord-014597-66vd2mdu 854 15 , , , cord-014597-66vd2mdu 854 16 fermentation fermentation NN cord-014597-66vd2mdu 854 17 protocols protocol NNS cord-014597-66vd2mdu 854 18 , , , cord-014597-66vd2mdu 854 19 media medium NNS cord-014597-66vd2mdu 854 20 recipes recipe NNS cord-014597-66vd2mdu 854 21 , , , cord-014597-66vd2mdu 854 22 bioreactor bioreactor NN cord-014597-66vd2mdu 854 23 control control NN cord-014597-66vd2mdu 854 24 parameters parameter NNS cord-014597-66vd2mdu 854 25 ) ) -RRB- cord-014597-66vd2mdu 854 26 is be VBZ cord-014597-66vd2mdu 854 27 not not RB cord-014597-66vd2mdu 854 28 easily easily RB cord-014597-66vd2mdu 854 29 accomplished accomplish VBN cord-014597-66vd2mdu 854 30 in in IN cord-014597-66vd2mdu 854 31 high high JJ cord-014597-66vd2mdu 854 32 throughput throughput NN cord-014597-66vd2mdu 854 33 . . . cord-014597-66vd2mdu 855 1 The the DT cord-014597-66vd2mdu 855 2 data datum NNS cord-014597-66vd2mdu 855 3 generated generate VBN cord-014597-66vd2mdu 855 4 in in IN cord-014597-66vd2mdu 855 5 the the DT cord-014597-66vd2mdu 855 6 process process NN cord-014597-66vd2mdu 855 7 must must MD cord-014597-66vd2mdu 855 8 not not RB cord-014597-66vd2mdu 855 9 only only RB cord-014597-66vd2mdu 855 10 be be VB cord-014597-66vd2mdu 855 11 analyzed analyze VBN cord-014597-66vd2mdu 855 12 , , , cord-014597-66vd2mdu 855 13 but but CC cord-014597-66vd2mdu 855 14 also also RB cord-014597-66vd2mdu 855 15 managed manage VBD cord-014597-66vd2mdu 855 16 and and CC cord-014597-66vd2mdu 855 17 stored store VBN cord-014597-66vd2mdu 855 18 to to TO cord-014597-66vd2mdu 855 19 enable enable VB cord-014597-66vd2mdu 855 20 easy easy JJ cord-014597-66vd2mdu 855 21 tracking tracking NN cord-014597-66vd2mdu 855 22 and and CC cord-014597-66vd2mdu 855 23 relating relate VBG cord-014597-66vd2mdu 855 24 to to IN cord-014597-66vd2mdu 855 25 historical historical JJ cord-014597-66vd2mdu 855 26 records record NNS cord-014597-66vd2mdu 855 27 . . . cord-014597-66vd2mdu 856 1 Furthermore furthermore RB cord-014597-66vd2mdu 856 2 , , , cord-014597-66vd2mdu 856 3 the the DT cord-014597-66vd2mdu 856 4 processes process NNS cord-014597-66vd2mdu 856 5 are be VBP cord-014597-66vd2mdu 856 6 often often RB cord-014597-66vd2mdu 856 7 developed develop VBN cord-014597-66vd2mdu 856 8 by by IN cord-014597-66vd2mdu 856 9 global global JJ cord-014597-66vd2mdu 856 10 teams team NNS cord-014597-66vd2mdu 856 11 interacting interact VBG cord-014597-66vd2mdu 856 12 in in IN cord-014597-66vd2mdu 856 13 complex complex JJ cord-014597-66vd2mdu 856 14 enterprise enterprise NN cord-014597-66vd2mdu 856 15 IT it NN cord-014597-66vd2mdu 856 16 ecosystems ecosystem VBZ cord-014597-66vd2mdu 856 17 . . . cord-014597-66vd2mdu 857 1 Therefore therefore RB cord-014597-66vd2mdu 857 2 , , , cord-014597-66vd2mdu 857 3 new new JJ cord-014597-66vd2mdu 857 4 and and CC cord-014597-66vd2mdu 857 5 high high JJ cord-014597-66vd2mdu 857 6 performing perform VBG cord-014597-66vd2mdu 857 7 systems system NNS cord-014597-66vd2mdu 857 8 for for IN cord-014597-66vd2mdu 857 9 data datum NNS cord-014597-66vd2mdu 857 10 capture capture NN cord-014597-66vd2mdu 857 11 , , , cord-014597-66vd2mdu 857 12 processing processing NN cord-014597-66vd2mdu 857 13 , , , cord-014597-66vd2mdu 857 14 and and CC cord-014597-66vd2mdu 857 15 analysis analysis NN cord-014597-66vd2mdu 857 16 need need VBP cord-014597-66vd2mdu 857 17 to to TO cord-014597-66vd2mdu 857 18 be be VB cord-014597-66vd2mdu 857 19 integrated integrate VBN cord-014597-66vd2mdu 857 20 in in IN cord-014597-66vd2mdu 857 21 order order NN cord-014597-66vd2mdu 857 22 to to TO cord-014597-66vd2mdu 857 23 enable enable VB cord-014597-66vd2mdu 857 24 storage storage NN cord-014597-66vd2mdu 857 25 and and CC cord-014597-66vd2mdu 857 26 correlation correlation NN cord-014597-66vd2mdu 857 27 of of IN cord-014597-66vd2mdu 857 28 experimental experimental JJ cord-014597-66vd2mdu 857 29 context context NN cord-014597-66vd2mdu 857 30 information information NN cord-014597-66vd2mdu 857 31 and and CC cord-014597-66vd2mdu 857 32 various various JJ cord-014597-66vd2mdu 857 33 types type NNS cord-014597-66vd2mdu 857 34 of of IN cord-014597-66vd2mdu 857 35 time time NN cord-014597-66vd2mdu 857 36 course course NN cord-014597-66vd2mdu 857 37 analytics analytics NNP cord-014597-66vd2mdu 857 38 data datum NNS cord-014597-66vd2mdu 857 39 . . . cord-014597-66vd2mdu 858 1 We -PRON- PRP cord-014597-66vd2mdu 858 2 have have VBP cord-014597-66vd2mdu 858 3 developed develop VBN cord-014597-66vd2mdu 858 4 Genedata Genedata NNP cord-014597-66vd2mdu 858 5 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 858 6 ™ ™ NN cord-014597-66vd2mdu 858 7 , , , cord-014597-66vd2mdu 858 8 a a DT cord-014597-66vd2mdu 858 9 new new JJ cord-014597-66vd2mdu 858 10 enterprise enterprise NN cord-014597-66vd2mdu 858 11 platform platform NN cord-014597-66vd2mdu 858 12 for for IN cord-014597-66vd2mdu 858 13 bioprocess bioprocess NNP cord-014597-66vd2mdu 858 14 development development NN cord-014597-66vd2mdu 858 15 . . . cord-014597-66vd2mdu 859 1 The the DT cord-014597-66vd2mdu 859 2 platform platform NN cord-014597-66vd2mdu 859 3 enables enable VBZ cord-014597-66vd2mdu 859 4 automatic automatic JJ cord-014597-66vd2mdu 859 5 capture capture NN cord-014597-66vd2mdu 859 6 and and CC cord-014597-66vd2mdu 859 7 visualization visualization NN cord-014597-66vd2mdu 859 8 of of IN cord-014597-66vd2mdu 859 9 all all DT cord-014597-66vd2mdu 859 10 online online JJ cord-014597-66vd2mdu 859 11 and and CC cord-014597-66vd2mdu 859 12 offline offline JJ cord-014597-66vd2mdu 859 13 data datum NNS cord-014597-66vd2mdu 859 14 ( ( -LRB- cord-014597-66vd2mdu 859 15 e.g. e.g. RB cord-014597-66vd2mdu 859 16 , , , cord-014597-66vd2mdu 859 17 pH pH NNP cord-014597-66vd2mdu 859 18 , , , cord-014597-66vd2mdu 859 19 O2 O2 NNP cord-014597-66vd2mdu 859 20 , , , cord-014597-66vd2mdu 859 21 metabolic metabolic JJ cord-014597-66vd2mdu 859 22 data datum NNS cord-014597-66vd2mdu 859 23 ) ) -RRB- cord-014597-66vd2mdu 859 24 , , , cord-014597-66vd2mdu 859 25 auto auto NN cord-014597-66vd2mdu 859 26 - - HYPH cord-014597-66vd2mdu 859 27 calculations calculation NNS cord-014597-66vd2mdu 859 28 and and CC cord-014597-66vd2mdu 859 29 aggregations aggregation NNS cord-014597-66vd2mdu 859 30 ( ( -LRB- cord-014597-66vd2mdu 859 31 e.g. e.g. RB cord-014597-66vd2mdu 859 32 , , , cord-014597-66vd2mdu 859 33 IVCD IVCD NNP cord-014597-66vd2mdu 859 34 , , , cord-014597-66vd2mdu 859 35 qP qP NNP cord-014597-66vd2mdu 859 36 , , , cord-014597-66vd2mdu 859 37 consumption consumption NN cord-014597-66vd2mdu 859 38 rates rate NNS cord-014597-66vd2mdu 859 39 ) ) -RRB- cord-014597-66vd2mdu 859 40 and and CC cord-014597-66vd2mdu 859 41 multi multi JJ cord-014597-66vd2mdu 859 42 - - JJ cord-014597-66vd2mdu 859 43 parametric parametric JJ cord-014597-66vd2mdu 859 44 assessment assessment NN cord-014597-66vd2mdu 859 45 of of IN cord-014597-66vd2mdu 859 46 any any DT cord-014597-66vd2mdu 859 47 type type NN cord-014597-66vd2mdu 859 48 of of IN cord-014597-66vd2mdu 859 49 time time NN cord-014597-66vd2mdu 859 50 - - HYPH cord-014597-66vd2mdu 859 51 series series NN cord-014597-66vd2mdu 859 52 bioreactor bioreactor NN cord-014597-66vd2mdu 859 53 data datum NNS cord-014597-66vd2mdu 859 54 in in IN cord-014597-66vd2mdu 859 55 the the DT cord-014597-66vd2mdu 859 56 context context NN cord-014597-66vd2mdu 859 57 of of IN cord-014597-66vd2mdu 859 58 experimental experimental JJ cord-014597-66vd2mdu 859 59 protocol protocol NN cord-014597-66vd2mdu 859 60 data datum NNS cord-014597-66vd2mdu 859 61 ( ( -LRB- cord-014597-66vd2mdu 859 62 e.g. e.g. RB cord-014597-66vd2mdu 859 63 , , , cord-014597-66vd2mdu 859 64 process process NN cord-014597-66vd2mdu 859 65 parameters parameter NNS cord-014597-66vd2mdu 859 66 , , , cord-014597-66vd2mdu 859 67 feeds feed VBZ cord-014597-66vd2mdu 859 68 ) ) -RRB- cord-014597-66vd2mdu 859 69 . . . cord-014597-66vd2mdu 860 1 Genedata Genedata NNP cord-014597-66vd2mdu 860 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 860 3 comes come VBZ cord-014597-66vd2mdu 860 4 with with IN cord-014597-66vd2mdu 860 5 dedicated dedicated JJ cord-014597-66vd2mdu 860 6 interfaces interface NNS cord-014597-66vd2mdu 860 7 for for IN cord-014597-66vd2mdu 860 8 integrating integrate VBG cord-014597-66vd2mdu 860 9 with with IN cord-014597-66vd2mdu 860 10 relevant relevant JJ cord-014597-66vd2mdu 860 11 laboratory laboratory NN cord-014597-66vd2mdu 860 12 instruments instrument NNS cord-014597-66vd2mdu 860 13 , , , cord-014597-66vd2mdu 860 14 control control NN cord-014597-66vd2mdu 860 15 systems system NNS cord-014597-66vd2mdu 860 16 , , , cord-014597-66vd2mdu 860 17 statistical statistical JJ cord-014597-66vd2mdu 860 18 analysis analysis NN cord-014597-66vd2mdu 860 19 software software NN cord-014597-66vd2mdu 860 20 packages package NNS cord-014597-66vd2mdu 860 21 and and CC cord-014597-66vd2mdu 860 22 custom custom NN cord-014597-66vd2mdu 860 23 enterprise enterprise NN cord-014597-66vd2mdu 860 24 solutions solution NNS cord-014597-66vd2mdu 860 25 . . . cord-014597-66vd2mdu 861 1 It -PRON- PRP cord-014597-66vd2mdu 861 2 enables enable VBZ cord-014597-66vd2mdu 861 3 the the DT cord-014597-66vd2mdu 861 4 modeling modeling NN cord-014597-66vd2mdu 861 5 and and CC cord-014597-66vd2mdu 861 6 tracking tracking NN cord-014597-66vd2mdu 861 7 of of IN cord-014597-66vd2mdu 861 8 complex complex JJ cord-014597-66vd2mdu 861 9 nonlinear nonlinear JJ cord-014597-66vd2mdu 861 10 workflows workflow NNS cord-014597-66vd2mdu 861 11 and and CC cord-014597-66vd2mdu 861 12 supports support VBZ cord-014597-66vd2mdu 861 13 decision decision NN cord-014597-66vd2mdu 861 14 making make VBG cord-014597-66vd2mdu 861 15 in in IN cord-014597-66vd2mdu 861 16 bioprocess bioprocess NN cord-014597-66vd2mdu 861 17 development development NN cord-014597-66vd2mdu 861 18 . . . cord-014597-66vd2mdu 862 1 The the DT cord-014597-66vd2mdu 862 2 data datum NNS cord-014597-66vd2mdu 862 3 can can MD cord-014597-66vd2mdu 862 4 be be VB cord-014597-66vd2mdu 862 5 analyzed analyze VBN cord-014597-66vd2mdu 862 6 in in IN cord-014597-66vd2mdu 862 7 the the DT cord-014597-66vd2mdu 862 8 context context NN cord-014597-66vd2mdu 862 9 of of IN cord-014597-66vd2mdu 862 10 upstream upstream JJ cord-014597-66vd2mdu 862 11 process process NN cord-014597-66vd2mdu 862 12 development development NN cord-014597-66vd2mdu 862 13 , , , cord-014597-66vd2mdu 862 14 and and CC cord-014597-66vd2mdu 862 15 also also RB cord-014597-66vd2mdu 862 16 be be VB cord-014597-66vd2mdu 862 17 correlated correlate VBN cord-014597-66vd2mdu 862 18 to to IN cord-014597-66vd2mdu 862 19 other other JJ cord-014597-66vd2mdu 862 20 unit unit NN cord-014597-66vd2mdu 862 21 operations operation NNS cord-014597-66vd2mdu 862 22 . . . cord-014597-66vd2mdu 863 1 Automation automation NN cord-014597-66vd2mdu 863 2 support support NN cord-014597-66vd2mdu 863 3 assists assist VBZ cord-014597-66vd2mdu 863 4 the the DT cord-014597-66vd2mdu 863 5 ever ever RB cord-014597-66vd2mdu 863 6 increasing increase VBG cord-014597-66vd2mdu 863 7 throughput throughput NN cord-014597-66vd2mdu 863 8 of of IN cord-014597-66vd2mdu 863 9 bioprocess bioprocess NN cord-014597-66vd2mdu 863 10 development development NN cord-014597-66vd2mdu 863 11 operations operation NNS cord-014597-66vd2mdu 863 12 , , , cord-014597-66vd2mdu 863 13 and and CC cord-014597-66vd2mdu 863 14 the the DT cord-014597-66vd2mdu 863 15 analysis analysis NN cord-014597-66vd2mdu 863 16 of of IN cord-014597-66vd2mdu 863 17 experimental experimental JJ cord-014597-66vd2mdu 863 18 data datum NNS cord-014597-66vd2mdu 863 19 and and CC cord-014597-66vd2mdu 863 20 process process NN cord-014597-66vd2mdu 863 21 parameters parameter NNS cord-014597-66vd2mdu 863 22 across across IN cord-014597-66vd2mdu 863 23 unit unit NN cord-014597-66vd2mdu 863 24 operations operation NNS cord-014597-66vd2mdu 863 25 or or CC cord-014597-66vd2mdu 863 26 even even RB cord-014597-66vd2mdu 863 27 different different JJ cord-014597-66vd2mdu 863 28 projects project NNS cord-014597-66vd2mdu 863 29 . . . cord-014597-66vd2mdu 864 1 This this DT cord-014597-66vd2mdu 864 2 overall overall JJ cord-014597-66vd2mdu 864 3 integration integration NN cord-014597-66vd2mdu 864 4 enhances enhance VBZ cord-014597-66vd2mdu 864 5 process process NN cord-014597-66vd2mdu 864 6 development development NN cord-014597-66vd2mdu 864 7 workflows workflow NNS cord-014597-66vd2mdu 864 8 . . . cord-014597-66vd2mdu 865 1 Highlighted highlight VBN cord-014597-66vd2mdu 865 2 use use NN cord-014597-66vd2mdu 865 3 cases case NNS cord-014597-66vd2mdu 865 4 describe describe VBP cord-014597-66vd2mdu 865 5 the the DT cord-014597-66vd2mdu 865 6 selection selection NN cord-014597-66vd2mdu 865 7 of of IN cord-014597-66vd2mdu 865 8 the the DT cord-014597-66vd2mdu 865 9 best good JJS cord-014597-66vd2mdu 865 10 producer producer NN cord-014597-66vd2mdu 865 11 clones clone NNS cord-014597-66vd2mdu 865 12 ( ( -LRB- cord-014597-66vd2mdu 865 13 Fig Fig NNP cord-014597-66vd2mdu 865 14 . . . cord-014597-66vd2mdu 865 15 1a 1a CD cord-014597-66vd2mdu 865 16 ) ) -RRB- cord-014597-66vd2mdu 865 17 , , , cord-014597-66vd2mdu 865 18 the the DT cord-014597-66vd2mdu 865 19 identification identification NN cord-014597-66vd2mdu 865 20 of of IN cord-014597-66vd2mdu 865 21 optimized optimize VBN cord-014597-66vd2mdu 865 22 media medium NNS cord-014597-66vd2mdu 865 23 feeding feeding NN cord-014597-66vd2mdu 865 24 strategies strategy NNS cord-014597-66vd2mdu 865 25 ( ( -LRB- cord-014597-66vd2mdu 865 26 Fig Fig NNP cord-014597-66vd2mdu 865 27 . . . cord-014597-66vd2mdu 865 28 1b 1b CD cord-014597-66vd2mdu 865 29 ) ) -RRB- cord-014597-66vd2mdu 865 30 , , , cord-014597-66vd2mdu 865 31 and and CC cord-014597-66vd2mdu 865 32 the the DT cord-014597-66vd2mdu 865 33 comparison comparison NN cord-014597-66vd2mdu 865 34 of of IN cord-014597-66vd2mdu 865 35 clone clone NN cord-014597-66vd2mdu 865 36 performance performance NN cord-014597-66vd2mdu 865 37 across across IN cord-014597-66vd2mdu 865 38 different different JJ cord-014597-66vd2mdu 865 39 fermentation fermentation NN cord-014597-66vd2mdu 865 40 scales scale NNS cord-014597-66vd2mdu 865 41 ( ( -LRB- cord-014597-66vd2mdu 865 42 Fig Fig NNP cord-014597-66vd2mdu 865 43 . . . cord-014597-66vd2mdu 865 44 1c 1c CD cord-014597-66vd2mdu 865 45 ) ) -RRB- cord-014597-66vd2mdu 865 46 . . . cord-014597-66vd2mdu 866 1 A a DT cord-014597-66vd2mdu 866 2 special special JJ cord-014597-66vd2mdu 866 3 focus focus NN cord-014597-66vd2mdu 866 4 is be VBZ cord-014597-66vd2mdu 866 5 on on IN cord-014597-66vd2mdu 866 6 the the DT cord-014597-66vd2mdu 866 7 analysis analysis NN cord-014597-66vd2mdu 866 8 of of IN cord-014597-66vd2mdu 866 9 data datum NNS cord-014597-66vd2mdu 866 10 from from IN cord-014597-66vd2mdu 866 11 micro micro JJ cord-014597-66vd2mdu 866 12 - - HYPH cord-014597-66vd2mdu 866 13 and and CC cord-014597-66vd2mdu 866 14 bench bench NN cord-014597-66vd2mdu 866 15 - - HYPH cord-014597-66vd2mdu 866 16 top top NN cord-014597-66vd2mdu 866 17 bioreactors bioreactor NNS cord-014597-66vd2mdu 866 18 ( ( -LRB- cord-014597-66vd2mdu 866 19 such such JJ cord-014597-66vd2mdu 866 20 as as IN cord-014597-66vd2mdu 866 21 the the DT cord-014597-66vd2mdu 866 22 ambr15 ambr15 NN cord-014597-66vd2mdu 866 23 ™ ™ NN cord-014597-66vd2mdu 866 24 and and CC cord-014597-66vd2mdu 866 25 DasGip DasGip NNP cord-014597-66vd2mdu 866 26 ™ ™ NNP cord-014597-66vd2mdu 866 27 systems system NNS cord-014597-66vd2mdu 866 28 ) ) -RRB- cord-014597-66vd2mdu 866 29 operated operate VBD cord-014597-66vd2mdu 866 30 in in IN cord-014597-66vd2mdu 866 31 parallel parallel NN cord-014597-66vd2mdu 866 32 . . . cord-014597-66vd2mdu 867 1 These these DT cord-014597-66vd2mdu 867 2 bioreactors bioreactor NNS cord-014597-66vd2mdu 867 3 allow allow VBP cord-014597-66vd2mdu 867 4 for for IN cord-014597-66vd2mdu 867 5 increased increase VBN cord-014597-66vd2mdu 867 6 throughput throughput NN cord-014597-66vd2mdu 867 7 of of IN cord-014597-66vd2mdu 867 8 clone clone NN cord-014597-66vd2mdu 867 9 selection selection NN cord-014597-66vd2mdu 867 10 and and CC cord-014597-66vd2mdu 867 11 process process NN cord-014597-66vd2mdu 867 12 optimization optimization NN cord-014597-66vd2mdu 867 13 studies study NNS cord-014597-66vd2mdu 867 14 , , , cord-014597-66vd2mdu 867 15 which which WDT cord-014597-66vd2mdu 867 16 in in IN cord-014597-66vd2mdu 867 17 turn turn NN cord-014597-66vd2mdu 867 18 leads lead VBZ cord-014597-66vd2mdu 867 19 to to IN cord-014597-66vd2mdu 867 20 an an DT cord-014597-66vd2mdu 867 21 increase increase NN cord-014597-66vd2mdu 867 22 in in IN cord-014597-66vd2mdu 867 23 data datum NNS cord-014597-66vd2mdu 867 24 generation generation NN cord-014597-66vd2mdu 867 25 . . . cord-014597-66vd2mdu 868 1 Genedata Genedata NNP cord-014597-66vd2mdu 868 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 868 3 supports support VBZ cord-014597-66vd2mdu 868 4 integration integration NN cord-014597-66vd2mdu 868 5 with with IN cord-014597-66vd2mdu 868 6 such such JJ cord-014597-66vd2mdu 868 7 systems system NNS cord-014597-66vd2mdu 868 8 and and CC cord-014597-66vd2mdu 868 9 enables enable VBZ cord-014597-66vd2mdu 868 10 a a DT cord-014597-66vd2mdu 868 11 comparison comparison NN cord-014597-66vd2mdu 868 12 of of IN cord-014597-66vd2mdu 868 13 data datum NNS cord-014597-66vd2mdu 868 14 regardless regardless RB cord-014597-66vd2mdu 868 15 of of IN cord-014597-66vd2mdu 868 16 the the DT cord-014597-66vd2mdu 868 17 instrument instrument NN cord-014597-66vd2mdu 868 18 provider provider NN cord-014597-66vd2mdu 868 19 or or CC cord-014597-66vd2mdu 868 20 scale scale NN cord-014597-66vd2mdu 868 21 . . . cord-014597-66vd2mdu 869 1 Automated automate VBN cord-014597-66vd2mdu 869 2 bioreactor bioreactor NN cord-014597-66vd2mdu 869 3 data datum NNS cord-014597-66vd2mdu 869 4 analysis analysis NN cord-014597-66vd2mdu 869 5 allows allow VBZ cord-014597-66vd2mdu 869 6 development development NN cord-014597-66vd2mdu 869 7 groups group NNS cord-014597-66vd2mdu 869 8 to to TO cord-014597-66vd2mdu 869 9 take take VB cord-014597-66vd2mdu 869 10 advantage advantage NN cord-014597-66vd2mdu 869 11 of of IN cord-014597-66vd2mdu 869 12 even even RB cord-014597-66vd2mdu 869 13 richer rich JJR cord-014597-66vd2mdu 869 14 datasets dataset NNS cord-014597-66vd2mdu 869 15 and and CC cord-014597-66vd2mdu 869 16 , , , cord-014597-66vd2mdu 869 17 as as IN cord-014597-66vd2mdu 869 18 data data NN cord-014597-66vd2mdu 869 19 management management NN cord-014597-66vd2mdu 869 20 is be VBZ cord-014597-66vd2mdu 869 21 built build VBN cord-014597-66vd2mdu 869 22 - - HYPH cord-014597-66vd2mdu 869 23 in in RP cord-014597-66vd2mdu 869 24 to to IN cord-014597-66vd2mdu 869 25 the the DT cord-014597-66vd2mdu 869 26 system system NN cord-014597-66vd2mdu 869 27 , , , cord-014597-66vd2mdu 869 28 the the DT cord-014597-66vd2mdu 869 29 data datum NNS cord-014597-66vd2mdu 869 30 can can MD cord-014597-66vd2mdu 869 31 be be VB cord-014597-66vd2mdu 869 32 easily easily RB cord-014597-66vd2mdu 869 33 tracked track VBN cord-014597-66vd2mdu 869 34 and and CC cord-014597-66vd2mdu 869 35 associated associate VBN cord-014597-66vd2mdu 869 36 to to IN cord-014597-66vd2mdu 869 37 historical historical JJ cord-014597-66vd2mdu 869 38 records record NNS cord-014597-66vd2mdu 869 39 . . . cord-014597-66vd2mdu 870 1 Another another DT cord-014597-66vd2mdu 870 2 focus focus NN cord-014597-66vd2mdu 870 3 is be VBZ cord-014597-66vd2mdu 870 4 on on IN cord-014597-66vd2mdu 870 5 cross cross JJ cord-014597-66vd2mdu 870 6 - - JJ cord-014597-66vd2mdu 870 7 reactor reactor JJ cord-014597-66vd2mdu 870 8 scale scale NN cord-014597-66vd2mdu 870 9 comparisons comparison NNS cord-014597-66vd2mdu 870 10 . . . cord-014597-66vd2mdu 871 1 Data datum NNS cord-014597-66vd2mdu 871 2 coming come VBG cord-014597-66vd2mdu 871 3 from from IN cord-014597-66vd2mdu 871 4 different different JJ cord-014597-66vd2mdu 871 5 bioreactor bioreactor NN cord-014597-66vd2mdu 871 6 scales scale NNS cord-014597-66vd2mdu 871 7 can can MD cord-014597-66vd2mdu 871 8 be be VB cord-014597-66vd2mdu 871 9 easily easily RB cord-014597-66vd2mdu 871 10 imported import VBN cord-014597-66vd2mdu 871 11 into into IN cord-014597-66vd2mdu 871 12 the the DT cord-014597-66vd2mdu 871 13 platform platform NN cord-014597-66vd2mdu 871 14 and and CC cord-014597-66vd2mdu 871 15 analyzed analyze VBD cord-014597-66vd2mdu 871 16 to to TO cord-014597-66vd2mdu 871 17 establish establish VB cord-014597-66vd2mdu 871 18 the the DT cord-014597-66vd2mdu 871 19 best good JJS cord-014597-66vd2mdu 871 20 conditions condition NNS cord-014597-66vd2mdu 871 21 for for IN cord-014597-66vd2mdu 871 22 upscaling upscaling NN cord-014597-66vd2mdu 871 23 . . . cord-014597-66vd2mdu 872 1 Genedata Genedata NNP cord-014597-66vd2mdu 872 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 872 3 enables enable VBZ cord-014597-66vd2mdu 872 4 the the DT cord-014597-66vd2mdu 872 5 correlation correlation NN cord-014597-66vd2mdu 872 6 of of IN cord-014597-66vd2mdu 872 7 process process NN cord-014597-66vd2mdu 872 8 parameters parameter NNS cord-014597-66vd2mdu 872 9 ( ( -LRB- cord-014597-66vd2mdu 872 10 e.g. e.g. RB cord-014597-66vd2mdu 872 11 , , , cord-014597-66vd2mdu 872 12 fermentation fermentation NN cord-014597-66vd2mdu 872 13 protocols protocol NNS cord-014597-66vd2mdu 872 14 , , , cord-014597-66vd2mdu 872 15 media medium NNS cord-014597-66vd2mdu 872 16 recipes recipe NNS cord-014597-66vd2mdu 872 17 , , , cord-014597-66vd2mdu 872 18 bioreactor bioreactor NN cord-014597-66vd2mdu 872 19 control control NN cord-014597-66vd2mdu 872 20 parameters parameter NNS cord-014597-66vd2mdu 872 21 ) ) -RRB- cord-014597-66vd2mdu 872 22 , , , cord-014597-66vd2mdu 872 23 with with IN cord-014597-66vd2mdu 872 24 key key JJ cord-014597-66vd2mdu 872 25 performance performance NN cord-014597-66vd2mdu 872 26 indicators indicator NNS cord-014597-66vd2mdu 872 27 of of IN cord-014597-66vd2mdu 872 28 the the DT cord-014597-66vd2mdu 872 29 processes process NNS cord-014597-66vd2mdu 872 30 ( ( -LRB- cord-014597-66vd2mdu 872 31 e.g. e.g. RB cord-014597-66vd2mdu 872 32 , , , cord-014597-66vd2mdu 872 33 Titer Titer NNP cord-014597-66vd2mdu 872 34 , , , cord-014597-66vd2mdu 872 35 qP qP NNP cord-014597-66vd2mdu 872 36 ) ) -RRB- cord-014597-66vd2mdu 872 37 and and CC cord-014597-66vd2mdu 872 38 the the DT cord-014597-66vd2mdu 872 39 product product NN cord-014597-66vd2mdu 872 40 quality quality NN cord-014597-66vd2mdu 872 41 attributes attribute NNS cord-014597-66vd2mdu 872 42 ( ( -LRB- cord-014597-66vd2mdu 872 43 e.g. e.g. RB cord-014597-66vd2mdu 872 44 , , , cord-014597-66vd2mdu 872 45 aggregation aggregation NN cord-014597-66vd2mdu 872 46 , , , cord-014597-66vd2mdu 872 47 glycosylation glycosylation NN cord-014597-66vd2mdu 872 48 profiles profile NNS cord-014597-66vd2mdu 872 49 ) ) -RRB- cord-014597-66vd2mdu 872 50 . . . cord-014597-66vd2mdu 873 1 Finally finally RB cord-014597-66vd2mdu 873 2 , , , cord-014597-66vd2mdu 873 3 bioreactor bioreactor NN cord-014597-66vd2mdu 873 4 time time NN cord-014597-66vd2mdu 873 5 course course NN cord-014597-66vd2mdu 873 6 data datum NNS cord-014597-66vd2mdu 873 7 can can MD cord-014597-66vd2mdu 873 8 be be VB cord-014597-66vd2mdu 873 9 tracked track VBN cord-014597-66vd2mdu 873 10 together together RB cord-014597-66vd2mdu 873 11 with with IN cord-014597-66vd2mdu 873 12 clone clone NN cord-014597-66vd2mdu 873 13 analytics analytic NNS cord-014597-66vd2mdu 873 14 and and CC cord-014597-66vd2mdu 873 15 product product NN cord-014597-66vd2mdu 873 16 quality quality NN cord-014597-66vd2mdu 873 17 parameters parameter NNS cord-014597-66vd2mdu 873 18 , , , cord-014597-66vd2mdu 873 19 which which WDT cord-014597-66vd2mdu 873 20 makes make VBZ cord-014597-66vd2mdu 873 21 the the DT cord-014597-66vd2mdu 873 22 platform platform NN cord-014597-66vd2mdu 873 23 uniquely uniquely RB cord-014597-66vd2mdu 873 24 able able JJ cord-014597-66vd2mdu 873 25 to to TO cord-014597-66vd2mdu 873 26 support support VB cord-014597-66vd2mdu 873 27 end end NN cord-014597-66vd2mdu 873 28 - - HYPH cord-014597-66vd2mdu 873 29 to to IN cord-014597-66vd2mdu 873 30 - - HYPH cord-014597-66vd2mdu 873 31 end end NN cord-014597-66vd2mdu 873 32 biopharma biopharma NN cord-014597-66vd2mdu 873 33 development development NN cord-014597-66vd2mdu 873 34 . . . cord-014597-66vd2mdu 874 1 Upstream upstream JJ cord-014597-66vd2mdu 874 2 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 874 3 are be VBP cord-014597-66vd2mdu 874 4 at at IN cord-014597-66vd2mdu 874 5 particular particular JJ cord-014597-66vd2mdu 874 6 risk risk NN cord-014597-66vd2mdu 874 7 of of IN cord-014597-66vd2mdu 874 8 contamination contamination NN cord-014597-66vd2mdu 874 9 from from IN cord-014597-66vd2mdu 874 10 adventitious adventitious JJ cord-014597-66vd2mdu 874 11 agents agent NNS cord-014597-66vd2mdu 874 12 . . . cord-014597-66vd2mdu 875 1 The the DT cord-014597-66vd2mdu 875 2 typical typical JJ cord-014597-66vd2mdu 875 3 0.1 0.1 CD cord-014597-66vd2mdu 875 4 μm μm NN cord-014597-66vd2mdu 875 5 filters filter NNS cord-014597-66vd2mdu 875 6 used use VBN cord-014597-66vd2mdu 875 7 at at IN cord-014597-66vd2mdu 875 8 this this DT cord-014597-66vd2mdu 875 9 step step NN cord-014597-66vd2mdu 875 10 protect protect VBP cord-014597-66vd2mdu 875 11 bioreactors bioreactor NNS cord-014597-66vd2mdu 875 12 from from IN cord-014597-66vd2mdu 875 13 bacteria bacteria NNS cord-014597-66vd2mdu 875 14 and and CC cord-014597-66vd2mdu 875 15 mycoplasma mycoplasma NN cord-014597-66vd2mdu 875 16 but but CC cord-014597-66vd2mdu 875 17 offer offer VBP cord-014597-66vd2mdu 875 18 no no DT cord-014597-66vd2mdu 875 19 protection protection NN cord-014597-66vd2mdu 875 20 from from IN cord-014597-66vd2mdu 875 21 viral viral JJ cord-014597-66vd2mdu 875 22 contaminations contamination NNS cord-014597-66vd2mdu 875 23 . . . cord-014597-66vd2mdu 876 1 A a DT cord-014597-66vd2mdu 876 2 new new JJ cord-014597-66vd2mdu 876 3 polyethersulfone polyethersulfone NNP cord-014597-66vd2mdu 876 4 ( ( -LRB- cord-014597-66vd2mdu 876 5 PES PES NNP cord-014597-66vd2mdu 876 6 ) ) -RRB- cord-014597-66vd2mdu 876 7 upstream upstream JJ cord-014597-66vd2mdu 876 8 virus virus NN cord-014597-66vd2mdu 876 9 filter filter NN cord-014597-66vd2mdu 876 10 , , , cord-014597-66vd2mdu 876 11 Viresolve Viresolve NNP cord-014597-66vd2mdu 876 12 ® ® NNP cord-014597-66vd2mdu 876 13 Barrier Barrier NNP cord-014597-66vd2mdu 876 14 , , , cord-014597-66vd2mdu 876 15 has have VBZ cord-014597-66vd2mdu 876 16 demonstrated demonstrate VBN cord-014597-66vd2mdu 876 17 high high JJ cord-014597-66vd2mdu 876 18 levels level NNS cord-014597-66vd2mdu 876 19 of of IN cord-014597-66vd2mdu 877 1 microorganism microorganism NNP cord-014597-66vd2mdu 877 2 retention retention NN cord-014597-66vd2mdu 877 3 -full -full VBZ cord-014597-66vd2mdu 877 4 retention retention NN cord-014597-66vd2mdu 877 5 for for IN cord-014597-66vd2mdu 877 6 bacteria bacteria NNS cord-014597-66vd2mdu 877 7 and and CC cord-014597-66vd2mdu 877 8 mycoplasma mycoplasma NN cord-014597-66vd2mdu 877 9 ( ( -LRB- cord-014597-66vd2mdu 877 10 > > NFP cord-014597-66vd2mdu 877 11 8.0 8.0 CD cord-014597-66vd2mdu 877 12 LRV lrv NN cord-014597-66vd2mdu 877 13 -Log -Log HYPH cord-014597-66vd2mdu 877 14 Reduction Reduction NNP cord-014597-66vd2mdu 877 15 Value Value NNP cord-014597-66vd2mdu 877 16 ) ) -RRB- cord-014597-66vd2mdu 877 17 and~5 and~5 JJ cord-014597-66vd2mdu 877 18 LRV lrv NN cord-014597-66vd2mdu 877 19 for for IN cord-014597-66vd2mdu 877 20 small small JJ cord-014597-66vd2mdu 877 21 viruses virus NNS cord-014597-66vd2mdu 877 22 , , , cord-014597-66vd2mdu 877 23 such such JJ cord-014597-66vd2mdu 877 24 as as IN cord-014597-66vd2mdu 877 25 parvoviruses parvovirus NNS cord-014597-66vd2mdu 877 26 . . . cord-014597-66vd2mdu 878 1 It -PRON- PRP cord-014597-66vd2mdu 878 2 also also RB cord-014597-66vd2mdu 878 3 has have VBZ cord-014597-66vd2mdu 878 4 improved improve VBN cord-014597-66vd2mdu 878 5 flow flow NN cord-014597-66vd2mdu 878 6 and and CC cord-014597-66vd2mdu 878 7 capacity capacity NN cord-014597-66vd2mdu 878 8 as as IN cord-014597-66vd2mdu 878 9 compared compare VBN cord-014597-66vd2mdu 878 10 to to IN cord-014597-66vd2mdu 878 11 virus virus NN cord-014597-66vd2mdu 878 12 removal removal NN cord-014597-66vd2mdu 878 13 filters filter NNS cord-014597-66vd2mdu 878 14 designed design VBN cord-014597-66vd2mdu 878 15 for for IN cord-014597-66vd2mdu 878 16 monoclonal monoclonal JJ cord-014597-66vd2mdu 878 17 antibody antibody NN cord-014597-66vd2mdu 878 18 purification purification NN cord-014597-66vd2mdu 878 19 . . . cord-014597-66vd2mdu 879 1 Given give VBN cord-014597-66vd2mdu 879 2 the the DT cord-014597-66vd2mdu 879 3 small small JJ cord-014597-66vd2mdu 879 4 pore pore NN cord-014597-66vd2mdu 879 5 size size NN cord-014597-66vd2mdu 879 6 of of IN cord-014597-66vd2mdu 879 7 virus virus NN cord-014597-66vd2mdu 879 8 retentive retentive JJ cord-014597-66vd2mdu 879 9 filters filter NNS cord-014597-66vd2mdu 879 10 , , , cord-014597-66vd2mdu 879 11 implementing implement VBG cord-014597-66vd2mdu 879 12 a a DT cord-014597-66vd2mdu 879 13 virus virus NN cord-014597-66vd2mdu 879 14 filter filter NN cord-014597-66vd2mdu 879 15 upstream upstream RB cord-014597-66vd2mdu 879 16 of of IN cord-014597-66vd2mdu 879 17 the the DT cord-014597-66vd2mdu 879 18 bioreactor bioreactor NN cord-014597-66vd2mdu 879 19 raises raise VBZ cord-014597-66vd2mdu 879 20 the the DT cord-014597-66vd2mdu 879 21 question question NN cord-014597-66vd2mdu 879 22 of of IN cord-014597-66vd2mdu 879 23 whether whether IN cord-014597-66vd2mdu 879 24 critical critical JJ cord-014597-66vd2mdu 879 25 cell cell NN cord-014597-66vd2mdu 879 26 culture culture NN cord-014597-66vd2mdu 879 27 media medium NNS cord-014597-66vd2mdu 879 28 components component NNS cord-014597-66vd2mdu 879 29 are be VBP cord-014597-66vd2mdu 879 30 removed remove VBN cord-014597-66vd2mdu 879 31 . . . cord-014597-66vd2mdu 880 1 Therefore therefore RB cord-014597-66vd2mdu 880 2 , , , cord-014597-66vd2mdu 880 3 it -PRON- PRP cord-014597-66vd2mdu 880 4 is be VBZ cord-014597-66vd2mdu 880 5 important important JJ cord-014597-66vd2mdu 880 6 to to TO cord-014597-66vd2mdu 880 7 evaluate evaluate VB cord-014597-66vd2mdu 880 8 the the DT cord-014597-66vd2mdu 880 9 cell cell NN cord-014597-66vd2mdu 880 10 culture culture NN cord-014597-66vd2mdu 880 11 performance performance NN cord-014597-66vd2mdu 880 12 and and CC cord-014597-66vd2mdu 880 13 protein protein NN cord-014597-66vd2mdu 880 14 quality quality NN cord-014597-66vd2mdu 880 15 attributes attribute NNS cord-014597-66vd2mdu 880 16 using use VBG cord-014597-66vd2mdu 880 17 virus virus NN cord-014597-66vd2mdu 880 18 - - HYPH cord-014597-66vd2mdu 880 19 filtered filter VBN cord-014597-66vd2mdu 880 20 media medium NNS cord-014597-66vd2mdu 880 21 to to TO cord-014597-66vd2mdu 880 22 ensure ensure VB cord-014597-66vd2mdu 880 23 that that IN cord-014597-66vd2mdu 880 24 filtration filtration NN cord-014597-66vd2mdu 880 25 does do VBZ cord-014597-66vd2mdu 880 26 not not RB cord-014597-66vd2mdu 880 27 negatively negatively RB cord-014597-66vd2mdu 880 28 impact impact VB cord-014597-66vd2mdu 880 29 the the DT cord-014597-66vd2mdu 880 30 process process NN cord-014597-66vd2mdu 880 31 . . . cord-014597-66vd2mdu 881 1 Materials material NNS cord-014597-66vd2mdu 881 2 and and CC cord-014597-66vd2mdu 881 3 methods method NNS cord-014597-66vd2mdu 881 4 EX ex NN cord-014597-66vd2mdu 881 5 - - HYPH cord-014597-66vd2mdu 881 6 CELL cell NN cord-014597-66vd2mdu 882 1 ® ® , cord-014597-66vd2mdu 882 2 CHO CHO NNP cord-014597-66vd2mdu 882 3 media medium NNS cord-014597-66vd2mdu 882 4 and and CC cord-014597-66vd2mdu 882 5 corresponding corresponding JJ cord-014597-66vd2mdu 882 6 feeds feed NNS cord-014597-66vd2mdu 882 7 were be VBD cord-014597-66vd2mdu 882 8 processed process VBN cord-014597-66vd2mdu 882 9 through through IN cord-014597-66vd2mdu 882 10 either either DT cord-014597-66vd2mdu 882 11 Viresolve Viresolve NNP cord-014597-66vd2mdu 882 12 ® ® . cord-014597-66vd2mdu 882 13 Barrier Barrier NNP cord-014597-66vd2mdu 882 14 filters filter NNS cord-014597-66vd2mdu 882 15 or or CC cord-014597-66vd2mdu 882 16 0.22 0.22 CD cord-014597-66vd2mdu 882 17 μm μm NN cord-014597-66vd2mdu 882 18 filters filter NNS cord-014597-66vd2mdu 882 19 ( ( -LRB- cord-014597-66vd2mdu 882 20 control control NN cord-014597-66vd2mdu 882 21 ) ) -RRB- cord-014597-66vd2mdu 882 22 . . . cord-014597-66vd2mdu 883 1 Media medium NNS cord-014597-66vd2mdu 883 2 composition composition NN cord-014597-66vd2mdu 883 3 post post NN cord-014597-66vd2mdu 883 4 - - NN cord-014597-66vd2mdu 883 5 filtration filtration NN cord-014597-66vd2mdu 883 6 was be VBD cord-014597-66vd2mdu 883 7 evaluated evaluate VBN cord-014597-66vd2mdu 883 8 by by IN cord-014597-66vd2mdu 883 9 high high JJ cord-014597-66vd2mdu 883 10 performance performance NN cord-014597-66vd2mdu 883 11 liquid liquid NN cord-014597-66vd2mdu 883 12 chromatography chromatography NN cord-014597-66vd2mdu 883 13 ( ( -LRB- cord-014597-66vd2mdu 883 14 HPLC HPLC NNP cord-014597-66vd2mdu 883 15 ) ) -RRB- cord-014597-66vd2mdu 883 16 , , , cord-014597-66vd2mdu 883 17 inductively inductively RB cord-014597-66vd2mdu 883 18 coupled couple VBN cord-014597-66vd2mdu 883 19 plasma/ plasma/ VBG cord-014597-66vd2mdu 883 20 optical optical JJ cord-014597-66vd2mdu 883 21 emission emission NN cord-014597-66vd2mdu 883 22 spectrometry spectrometry NN cord-014597-66vd2mdu 883 23 ( ( -LRB- cord-014597-66vd2mdu 883 24 ICP ICP NNP cord-014597-66vd2mdu 883 25 - - HYPH cord-014597-66vd2mdu 883 26 OES OES NNP cord-014597-66vd2mdu 883 27 ) ) -RRB- cord-014597-66vd2mdu 883 28 , , , cord-014597-66vd2mdu 883 29 and and CC cord-014597-66vd2mdu 883 30 nuclear nuclear JJ cord-014597-66vd2mdu 883 31 magnetic magnetic JJ cord-014597-66vd2mdu 883 32 resonance resonance NN cord-014597-66vd2mdu 883 33 ( ( -LRB- cord-014597-66vd2mdu 883 34 NMR NMR NNP cord-014597-66vd2mdu 883 35 ) ) -RRB- cord-014597-66vd2mdu 883 36 . . . cord-014597-66vd2mdu 884 1 Recombinant recombinant JJ cord-014597-66vd2mdu 884 2 CHO CHO NNP cord-014597-66vd2mdu 884 3 cells cell NNS cord-014597-66vd2mdu 884 4 were be VBD cord-014597-66vd2mdu 884 5 cultured culture VBN cord-014597-66vd2mdu 884 6 in in IN cord-014597-66vd2mdu 884 7 fed fed NNP cord-014597-66vd2mdu 884 8 batch batch NN cord-014597-66vd2mdu 884 9 culture culture NN cord-014597-66vd2mdu 884 10 . . . cord-014597-66vd2mdu 885 1 Cell cell NN cord-014597-66vd2mdu 885 2 density density NN cord-014597-66vd2mdu 885 3 and and CC cord-014597-66vd2mdu 885 4 viability viability NN cord-014597-66vd2mdu 885 5 were be VBD cord-014597-66vd2mdu 885 6 measured measure VBN cord-014597-66vd2mdu 885 7 by by IN cord-014597-66vd2mdu 885 8 Vi Vi NNP cord-014597-66vd2mdu 885 9 - - HYPH cord-014597-66vd2mdu 885 10 Cell Cell NNP cord-014597-66vd2mdu 885 11 TM TM NNP cord-014597-66vd2mdu 885 12 cell cell NN cord-014597-66vd2mdu 885 13 viability viability NN cord-014597-66vd2mdu 885 14 analyzer analyzer NN cord-014597-66vd2mdu 885 15 while while IN cord-014597-66vd2mdu 885 16 metabolites metabolite NNS cord-014597-66vd2mdu 885 17 were be VBD cord-014597-66vd2mdu 885 18 analyzed analyze VBN cord-014597-66vd2mdu 885 19 by by IN cord-014597-66vd2mdu 885 20 BioProfile BioProfile NNP cord-014597-66vd2mdu 885 21 ® ® SYM cord-014597-66vd2mdu 885 22 FLEX flex NN cord-014597-66vd2mdu 885 23 analyzer analyzer NN cord-014597-66vd2mdu 885 24 . . . cord-014597-66vd2mdu 886 1 Shake shake VB cord-014597-66vd2mdu 886 2 flasks flask NNS cord-014597-66vd2mdu 886 3 and and CC cord-014597-66vd2mdu 886 4 bioreactors bioreactor NNS cord-014597-66vd2mdu 886 5 were be VBD cord-014597-66vd2mdu 886 6 utilized utilize VBN cord-014597-66vd2mdu 886 7 to to TO cord-014597-66vd2mdu 886 8 verify verify VB cord-014597-66vd2mdu 886 9 that that IN cord-014597-66vd2mdu 886 10 surfactants surfactant NNS cord-014597-66vd2mdu 886 11 , , , cord-014597-66vd2mdu 886 12 such such JJ cord-014597-66vd2mdu 886 13 as as IN cord-014597-66vd2mdu 886 14 poloxamer poloxamer NNP cord-014597-66vd2mdu 886 15 , , , cord-014597-66vd2mdu 886 16 ( ( -LRB- cord-014597-66vd2mdu 886 17 which which WDT cord-014597-66vd2mdu 886 18 are be VBP cord-014597-66vd2mdu 886 19 essential essential JJ cord-014597-66vd2mdu 886 20 for for IN cord-014597-66vd2mdu 886 21 shear shear NN cord-014597-66vd2mdu 886 22 protection protection NN cord-014597-66vd2mdu 886 23 in in IN cord-014597-66vd2mdu 886 24 stirred stir VBN cord-014597-66vd2mdu 886 25 tank tank NN cord-014597-66vd2mdu 886 26 bioreactors bioreactor NNS cord-014597-66vd2mdu 886 27 and and CC cord-014597-66vd2mdu 886 28 can can MD cord-014597-66vd2mdu 886 29 be be VB cord-014597-66vd2mdu 886 30 difficult difficult JJ cord-014597-66vd2mdu 886 31 to to TO cord-014597-66vd2mdu 886 32 filter filter VB cord-014597-66vd2mdu 886 33 ) ) -RRB- cord-014597-66vd2mdu 886 34 have have VBP cord-014597-66vd2mdu 886 35 not not RB cord-014597-66vd2mdu 886 36 been be VBN cord-014597-66vd2mdu 886 37 removed remove VBN cord-014597-66vd2mdu 886 38 during during IN cord-014597-66vd2mdu 886 39 filtration filtration NN cord-014597-66vd2mdu 886 40 . . . cord-014597-66vd2mdu 887 1 Monoclonal monoclonal JJ cord-014597-66vd2mdu 887 2 antibody antibody NN cord-014597-66vd2mdu 887 3 titer titer NN cord-014597-66vd2mdu 887 4 was be VBD cord-014597-66vd2mdu 887 5 quantitated quantitate VBN cord-014597-66vd2mdu 887 6 by by IN cord-014597-66vd2mdu 887 7 Protein Protein NNP cord-014597-66vd2mdu 887 8 A a DT cord-014597-66vd2mdu 887 9 HPLC HPLC NNP cord-014597-66vd2mdu 887 10 . . . cord-014597-66vd2mdu 888 1 Characterization characterization NN cord-014597-66vd2mdu 888 2 of of IN cord-014597-66vd2mdu 888 3 the the DT cord-014597-66vd2mdu 888 4 antibody antibody NN cord-014597-66vd2mdu 888 5 product product NN cord-014597-66vd2mdu 888 6 quality quality NN cord-014597-66vd2mdu 888 7 was be VBD cord-014597-66vd2mdu 888 8 assessed assess VBN cord-014597-66vd2mdu 888 9 via via IN cord-014597-66vd2mdu 888 10 weak weak JJ cord-014597-66vd2mdu 888 11 cation cation NN cord-014597-66vd2mdu 888 12 - - HYPH cord-014597-66vd2mdu 888 13 exchange exchange NN cord-014597-66vd2mdu 888 14 chromatography chromatography NN cord-014597-66vd2mdu 888 15 ( ( -LRB- cord-014597-66vd2mdu 888 16 charge charge NN cord-014597-66vd2mdu 888 17 heterogeneity heterogeneity NN cord-014597-66vd2mdu 888 18 ) ) -RRB- cord-014597-66vd2mdu 888 19 , , , cord-014597-66vd2mdu 888 20 size size NN cord-014597-66vd2mdu 888 21 exclusion exclusion NN cord-014597-66vd2mdu 888 22 chromatography chromatography NN cord-014597-66vd2mdu 888 23 ( ( -LRB- cord-014597-66vd2mdu 888 24 aggregate aggregate NN cord-014597-66vd2mdu 888 25 profile profile NN cord-014597-66vd2mdu 888 26 ) ) -RRB- cord-014597-66vd2mdu 888 27 , , , cord-014597-66vd2mdu 888 28 and and CC cord-014597-66vd2mdu 888 29 2-AB 2-ab CD cord-014597-66vd2mdu 888 30 fluorescent fluorescent JJ cord-014597-66vd2mdu 888 31 labeling labeling NN cord-014597-66vd2mdu 888 32 with with IN cord-014597-66vd2mdu 888 33 NP NP NNP cord-014597-66vd2mdu 888 34 - - HYPH cord-014597-66vd2mdu 888 35 UPLC UPLC NNP cord-014597-66vd2mdu 888 36 ( ( -LRB- cord-014597-66vd2mdu 888 37 glycan glycan NN cord-014597-66vd2mdu 888 38 species specie NNS cord-014597-66vd2mdu 888 39 ) ) -RRB- cord-014597-66vd2mdu 888 40 . . . cord-014597-66vd2mdu 889 1 Media medium NNS cord-014597-66vd2mdu 889 2 and and CC cord-014597-66vd2mdu 889 3 feed feed NN cord-014597-66vd2mdu 889 4 compositions composition NNS cord-014597-66vd2mdu 889 5 were be VBD cord-014597-66vd2mdu 889 6 unaffected unaffected JJ cord-014597-66vd2mdu 889 7 by by IN cord-014597-66vd2mdu 889 8 filtration filtration NN cord-014597-66vd2mdu 889 9 through through IN cord-014597-66vd2mdu 889 10 the the DT cord-014597-66vd2mdu 889 11 virus virus NN cord-014597-66vd2mdu 889 12 barrier barrier NN cord-014597-66vd2mdu 889 13 filter filter NN cord-014597-66vd2mdu 889 14 . . . cord-014597-66vd2mdu 890 1 No no DT cord-014597-66vd2mdu 890 2 significant significant JJ cord-014597-66vd2mdu 890 3 differences difference NNS cord-014597-66vd2mdu 890 4 in in IN cord-014597-66vd2mdu 890 5 concentrations concentration NNS cord-014597-66vd2mdu 890 6 were be VBD cord-014597-66vd2mdu 890 7 observed observe VBN cord-014597-66vd2mdu 890 8 with with IN cord-014597-66vd2mdu 890 9 ICP ICP NNP cord-014597-66vd2mdu 890 10 - - HYPH cord-014597-66vd2mdu 890 11 OES OES NNP cord-014597-66vd2mdu 890 12 ( ( -LRB- cord-014597-66vd2mdu 890 13 trace trace NN cord-014597-66vd2mdu 890 14 metals metal NNS cord-014597-66vd2mdu 890 15 ) ) -RRB- cord-014597-66vd2mdu 890 16 or or CC cord-014597-66vd2mdu 890 17 HPLC HPLC NNP cord-014597-66vd2mdu 890 18 ( ( -LRB- cord-014597-66vd2mdu 890 19 amino amino NN cord-014597-66vd2mdu 890 20 acids acid NNS cord-014597-66vd2mdu 890 21 and and CC cord-014597-66vd2mdu 890 22 water water NN cord-014597-66vd2mdu 890 23 soluble soluble JJ cord-014597-66vd2mdu 890 24 vitamins vitamin NNS cord-014597-66vd2mdu 890 25 ) ) -RRB- cord-014597-66vd2mdu 890 26 . . . cord-014597-66vd2mdu 891 1 NMR NMR NNP cord-014597-66vd2mdu 891 2 showed show VBD cord-014597-66vd2mdu 891 3 no no DT cord-014597-66vd2mdu 891 4 change change NN cord-014597-66vd2mdu 891 5 in in IN cord-014597-66vd2mdu 891 6 the the DT cord-014597-66vd2mdu 891 7 organic organic JJ cord-014597-66vd2mdu 891 8 composition composition NN cord-014597-66vd2mdu 891 9 of of IN cord-014597-66vd2mdu 891 10 the the DT cord-014597-66vd2mdu 891 11 media medium NNS cord-014597-66vd2mdu 891 12 including include VBG cord-014597-66vd2mdu 891 13 poloxamer poloxamer NNP cord-014597-66vd2mdu 891 14 . . . cord-014597-66vd2mdu 892 1 The the DT cord-014597-66vd2mdu 892 2 aromatic aromatic JJ cord-014597-66vd2mdu 892 3 region region NN cord-014597-66vd2mdu 892 4 with with IN cord-014597-66vd2mdu 892 5 vitamin vitamin NN cord-014597-66vd2mdu 892 6 and and CC cord-014597-66vd2mdu 892 7 amino amino NN cord-014597-66vd2mdu 892 8 acid acid NN cord-014597-66vd2mdu 892 9 signals signal NNS cord-014597-66vd2mdu 892 10 is be VBZ cord-014597-66vd2mdu 892 11 shown show VBN cord-014597-66vd2mdu 892 12 ( ( -LRB- cord-014597-66vd2mdu 892 13 Fig Fig NNP cord-014597-66vd2mdu 892 14 . . . cord-014597-66vd2mdu 892 15 1a 1a CD cord-014597-66vd2mdu 892 16 ) ) -RRB- cord-014597-66vd2mdu 892 17 . . . cord-014597-66vd2mdu 893 1 Cell cell NN cord-014597-66vd2mdu 893 2 cultures culture NNS cord-014597-66vd2mdu 893 3 showed show VBD cord-014597-66vd2mdu 893 4 no no DT cord-014597-66vd2mdu 893 5 differences difference NNS cord-014597-66vd2mdu 893 6 in in IN cord-014597-66vd2mdu 893 7 cell cell NN cord-014597-66vd2mdu 893 8 growth growth NN cord-014597-66vd2mdu 893 9 or or CC cord-014597-66vd2mdu 893 10 titer titer NN cord-014597-66vd2mdu 893 11 , , , cord-014597-66vd2mdu 893 12 in in IN cord-014597-66vd2mdu 893 13 either either DT cord-014597-66vd2mdu 893 14 shake shake VB cord-014597-66vd2mdu 893 15 flasks flask NNS cord-014597-66vd2mdu 893 16 or or CC cord-014597-66vd2mdu 893 17 bioreactors bioreactor NNS cord-014597-66vd2mdu 893 18 ( ( -LRB- cord-014597-66vd2mdu 893 19 Fig fig NN cord-014597-66vd2mdu 893 20 . . . cord-014597-66vd2mdu 893 21 1b 1b CD cord-014597-66vd2mdu 893 22 ) ) -RRB- cord-014597-66vd2mdu 893 23 . . . cord-014597-66vd2mdu 894 1 Cell cell NN cord-014597-66vd2mdu 894 2 viability viability NN cord-014597-66vd2mdu 894 3 was be VBD cord-014597-66vd2mdu 894 4 unaffected unaffected JJ cord-014597-66vd2mdu 894 5 , , , cord-014597-66vd2mdu 894 6 metabolite metabolite JJ cord-014597-66vd2mdu 894 7 levels level NNS cord-014597-66vd2mdu 894 8 were be VBD cord-014597-66vd2mdu 894 9 within within IN cord-014597-66vd2mdu 894 10 limits limit NNS cord-014597-66vd2mdu 894 11 , , , cord-014597-66vd2mdu 894 12 and and CC cord-014597-66vd2mdu 894 13 titer titer NN cord-014597-66vd2mdu 894 14 was be VBD cord-014597-66vd2mdu 894 15 consistent consistent JJ cord-014597-66vd2mdu 894 16 . . . cord-014597-66vd2mdu 895 1 The the DT cord-014597-66vd2mdu 895 2 protein protein NN cord-014597-66vd2mdu 895 3 quality quality NN cord-014597-66vd2mdu 895 4 of of IN cord-014597-66vd2mdu 895 5 the the DT cord-014597-66vd2mdu 895 6 secreted secrete VBN cord-014597-66vd2mdu 895 7 antibodies antibody NNS cord-014597-66vd2mdu 895 8 showed show VBD cord-014597-66vd2mdu 895 9 no no DT cord-014597-66vd2mdu 895 10 differences difference NNS cord-014597-66vd2mdu 895 11 in in IN cord-014597-66vd2mdu 895 12 the the DT cord-014597-66vd2mdu 895 13 glycosylation glycosylation NN cord-014597-66vd2mdu 895 14 pattern pattern NN cord-014597-66vd2mdu 895 15 ( ( -LRB- cord-014597-66vd2mdu 895 16 Fig Fig NNP cord-014597-66vd2mdu 895 17 . . . cord-014597-66vd2mdu 895 18 1c 1c NNP cord-014597-66vd2mdu 895 19 ) ) -RRB- cord-014597-66vd2mdu 895 20 , , , cord-014597-66vd2mdu 895 21 amount amount NN cord-014597-66vd2mdu 895 22 of of IN cord-014597-66vd2mdu 895 23 aggregates aggregate NNS cord-014597-66vd2mdu 895 24 or or CC cord-014597-66vd2mdu 895 25 charge charge NN cord-014597-66vd2mdu 895 26 variants variant NNS cord-014597-66vd2mdu 895 27 . . . cord-014597-66vd2mdu 896 1 The the DT cord-014597-66vd2mdu 896 2 risk risk NN cord-014597-66vd2mdu 896 3 of of IN cord-014597-66vd2mdu 896 4 virus virus NN cord-014597-66vd2mdu 896 5 contamination contamination NN cord-014597-66vd2mdu 896 6 in in IN cord-014597-66vd2mdu 896 7 the the DT cord-014597-66vd2mdu 896 8 bioreactor bioreactor NN cord-014597-66vd2mdu 896 9 remains remain VBZ cord-014597-66vd2mdu 896 10 a a DT cord-014597-66vd2mdu 896 11 concern concern NN cord-014597-66vd2mdu 896 12 for for IN cord-014597-66vd2mdu 896 13 biotherapeutic biotherapeutic JJ cord-014597-66vd2mdu 896 14 manufacturers manufacturer NNS cord-014597-66vd2mdu 896 15 as as IN cord-014597-66vd2mdu 896 16 there there EX cord-014597-66vd2mdu 896 17 is be VBZ cord-014597-66vd2mdu 896 18 no no DT cord-014597-66vd2mdu 896 19 universal universal JJ cord-014597-66vd2mdu 896 20 technology technology NN cord-014597-66vd2mdu 896 21 that that WDT cord-014597-66vd2mdu 896 22 provides provide VBZ cord-014597-66vd2mdu 896 23 a a DT cord-014597-66vd2mdu 896 24 reliable reliable JJ cord-014597-66vd2mdu 896 25 , , , cord-014597-66vd2mdu 896 26 cost cost VBD cord-014597-66vd2mdu 896 27 effective effective JJ cord-014597-66vd2mdu 896 28 solution solution NN cord-014597-66vd2mdu 896 29 for for IN cord-014597-66vd2mdu 896 30 virus virus NN cord-014597-66vd2mdu 896 31 removal removal NN cord-014597-66vd2mdu 896 32 that that WDT cord-014597-66vd2mdu 896 33 can can MD cord-014597-66vd2mdu 896 34 be be VB cord-014597-66vd2mdu 896 35 applied apply VBN cord-014597-66vd2mdu 896 36 to to IN cord-014597-66vd2mdu 896 37 all all DT cord-014597-66vd2mdu 896 38 components component NNS cord-014597-66vd2mdu 896 39 of of IN cord-014597-66vd2mdu 896 40 cell cell NN cord-014597-66vd2mdu 896 41 culture culture NN cord-014597-66vd2mdu 896 42 media medium NNS cord-014597-66vd2mdu 896 43 . . . cord-014597-66vd2mdu 897 1 This this DT cord-014597-66vd2mdu 897 2 study study NN cord-014597-66vd2mdu 897 3 evaluated evaluate VBD cord-014597-66vd2mdu 897 4 the the DT cord-014597-66vd2mdu 897 5 Viresolve Viresolve NNP cord-014597-66vd2mdu 897 6 ® ® . cord-014597-66vd2mdu 897 7 Barrier Barrier NNP cord-014597-66vd2mdu 897 8 filter filter NN cord-014597-66vd2mdu 897 9 that that WDT cord-014597-66vd2mdu 897 10 provides provide VBZ cord-014597-66vd2mdu 897 11 an an DT cord-014597-66vd2mdu 897 12 efficient efficient JJ cord-014597-66vd2mdu 897 13 and and CC cord-014597-66vd2mdu 897 14 easy easy JJ cord-014597-66vd2mdu 897 15 way way NN cord-014597-66vd2mdu 897 16 to to TO cord-014597-66vd2mdu 897 17 protect protect VB cord-014597-66vd2mdu 897 18 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 897 19 from from IN cord-014597-66vd2mdu 897 20 adventitious adventitious JJ cord-014597-66vd2mdu 897 21 virus virus NN cord-014597-66vd2mdu 897 22 contamination contamination NN cord-014597-66vd2mdu 897 23 . . . cord-014597-66vd2mdu 898 1 Study study NN cord-014597-66vd2mdu 898 2 results result NNS cord-014597-66vd2mdu 898 3 demonstrated demonstrate VBD cord-014597-66vd2mdu 898 4 that that IN cord-014597-66vd2mdu 898 5 media medium NNS cord-014597-66vd2mdu 898 6 and and CC cord-014597-66vd2mdu 898 7 feed feed NN cord-014597-66vd2mdu 898 8 compositions composition NNS cord-014597-66vd2mdu 898 9 , , , cord-014597-66vd2mdu 898 10 cell cell NN cord-014597-66vd2mdu 898 11 culture culture NN cord-014597-66vd2mdu 898 12 performance performance NN cord-014597-66vd2mdu 898 13 , , , cord-014597-66vd2mdu 898 14 and and CC cord-014597-66vd2mdu 898 15 product product NN cord-014597-66vd2mdu 898 16 quality quality NN cord-014597-66vd2mdu 898 17 were be VBD cord-014597-66vd2mdu 898 18 unaffected unaffected JJ cord-014597-66vd2mdu 898 19 by by IN cord-014597-66vd2mdu 898 20 filtration filtration NN cord-014597-66vd2mdu 898 21 through through IN cord-014597-66vd2mdu 898 22 the the DT cord-014597-66vd2mdu 898 23 Viresolve Viresolve NNP cord-014597-66vd2mdu 898 24 ® ® . cord-014597-66vd2mdu 898 25 Barrier Barrier NNP cord-014597-66vd2mdu 898 26 filter filter NN cord-014597-66vd2mdu 898 27 . . . cord-014597-66vd2mdu 899 1 Implementation implementation NN cord-014597-66vd2mdu 899 2 of of IN cord-014597-66vd2mdu 899 3 Vire Vire NNP cord-014597-66vd2mdu 899 4 - - HYPH cord-014597-66vd2mdu 899 5 solve solve VB cord-014597-66vd2mdu 900 1 ® ® , cord-014597-66vd2mdu 900 2 Barrier Barrier NNP cord-014597-66vd2mdu 900 3 filters filter NNS cord-014597-66vd2mdu 900 4 provides provide VBZ cord-014597-66vd2mdu 900 5 efficient efficient JJ cord-014597-66vd2mdu 900 6 filtration filtration NN cord-014597-66vd2mdu 900 7 performance performance NN cord-014597-66vd2mdu 900 8 , , , cord-014597-66vd2mdu 900 9 high high JJ cord-014597-66vd2mdu 900 10 virus virus NN cord-014597-66vd2mdu 900 11 retention retention NN cord-014597-66vd2mdu 900 12 , , , cord-014597-66vd2mdu 900 13 and and CC cord-014597-66vd2mdu 900 14 minimal minimal JJ cord-014597-66vd2mdu 900 15 cell cell NN cord-014597-66vd2mdu 900 16 culture culture NN cord-014597-66vd2mdu 900 17 impact impact NN cord-014597-66vd2mdu 900 18 and and CC cord-014597-66vd2mdu 900 19 offers offer VBZ cord-014597-66vd2mdu 900 20 a a DT cord-014597-66vd2mdu 900 21 viable viable JJ cord-014597-66vd2mdu 900 22 option option NN cord-014597-66vd2mdu 900 23 to to TO cord-014597-66vd2mdu 900 24 improve improve VB cord-014597-66vd2mdu 900 25 the the DT cord-014597-66vd2mdu 900 26 overall overall JJ cord-014597-66vd2mdu 900 27 virus virus NN cord-014597-66vd2mdu 900 28 risk risk NN cord-014597-66vd2mdu 900 29 mitigation mitigation NN cord-014597-66vd2mdu 900 30 strategy strategy NN cord-014597-66vd2mdu 900 31 for for IN cord-014597-66vd2mdu 900 32 the the DT cord-014597-66vd2mdu 900 33 manufacture manufacture NN cord-014597-66vd2mdu 900 34 of of IN cord-014597-66vd2mdu 900 35 biotherapeutics biotherapeutic NNS cord-014597-66vd2mdu 900 36 . . . cord-014597-66vd2mdu 901 1 b b LS cord-014597-66vd2mdu 901 2 Tracking tracking NN cord-014597-66vd2mdu 901 3 of of IN cord-014597-66vd2mdu 901 4 process process NN cord-014597-66vd2mdu 901 5 conditions condition NNS cord-014597-66vd2mdu 901 6 together together RB cord-014597-66vd2mdu 901 7 with with IN cord-014597-66vd2mdu 901 8 online online JJ cord-014597-66vd2mdu 901 9 and and CC cord-014597-66vd2mdu 901 10 offline offline JJ cord-014597-66vd2mdu 901 11 performance performance NN cord-014597-66vd2mdu 901 12 analytics analytic NNS cord-014597-66vd2mdu 901 13 . . . cord-014597-66vd2mdu 902 1 The the DT cord-014597-66vd2mdu 902 2 system system NN cord-014597-66vd2mdu 902 3 allows allow VBZ cord-014597-66vd2mdu 902 4 to to TO cord-014597-66vd2mdu 902 5 flexibly flexibly RB cord-014597-66vd2mdu 902 6 define define VB cord-014597-66vd2mdu 902 7 tracked track VBN cord-014597-66vd2mdu 902 8 parameters parameter NNS cord-014597-66vd2mdu 902 9 and and CC cord-014597-66vd2mdu 902 10 select select VB cord-014597-66vd2mdu 902 11 optimal optimal JJ cord-014597-66vd2mdu 902 12 process process NN cord-014597-66vd2mdu 902 13 conditions condition NNS cord-014597-66vd2mdu 902 14 . . . cord-014597-66vd2mdu 903 1 c c LS cord-014597-66vd2mdu 903 2 Comparison comparison NN cord-014597-66vd2mdu 903 3 of of IN cord-014597-66vd2mdu 903 4 process process NN cord-014597-66vd2mdu 903 5 performance performance NN cord-014597-66vd2mdu 903 6 across across IN cord-014597-66vd2mdu 903 7 different different JJ cord-014597-66vd2mdu 903 8 reactor reactor NN cord-014597-66vd2mdu 903 9 scales scale NNS cord-014597-66vd2mdu 903 10 . . . cord-014597-66vd2mdu 904 1 The the DT cord-014597-66vd2mdu 904 2 open open JJ cord-014597-66vd2mdu 904 3 architecture architecture NN cord-014597-66vd2mdu 904 4 makes make VBZ cord-014597-66vd2mdu 904 5 Genedata Genedata NNP cord-014597-66vd2mdu 904 6 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 904 7 a a DT cord-014597-66vd2mdu 904 8 provider provider NN cord-014597-66vd2mdu 904 9 agnostic agnostic JJ cord-014597-66vd2mdu 904 10 system system NN cord-014597-66vd2mdu 904 11 which which WDT cord-014597-66vd2mdu 904 12 allows allow VBZ cord-014597-66vd2mdu 904 13 to to TO cord-014597-66vd2mdu 904 14 aggregate aggregate VB cord-014597-66vd2mdu 904 15 and and CC cord-014597-66vd2mdu 904 16 compare compare VB cord-014597-66vd2mdu 904 17 data datum NNS cord-014597-66vd2mdu 904 18 regardless regardless RB cord-014597-66vd2mdu 904 19 of of IN cord-014597-66vd2mdu 904 20 provider provider NN cord-014597-66vd2mdu 904 21 Background Background NNP cord-014597-66vd2mdu 904 22 Bi Bi NNP cord-014597-66vd2mdu 904 23 - - : cord-014597-66vd2mdu 904 24 and and CC cord-014597-66vd2mdu 904 25 multi multi JJ cord-014597-66vd2mdu 904 26 - - JJ cord-014597-66vd2mdu 904 27 specific specific JJ cord-014597-66vd2mdu 904 28 antibodies antibody NNS cord-014597-66vd2mdu 904 29 , , , cord-014597-66vd2mdu 904 30 antibody antibody NN cord-014597-66vd2mdu 904 31 - - HYPH cord-014597-66vd2mdu 904 32 cytokine cytokine NN cord-014597-66vd2mdu 904 33 fusion fusion NN cord-014597-66vd2mdu 904 34 proteins protein NNS cord-014597-66vd2mdu 904 35 , , , cord-014597-66vd2mdu 904 36 nonimmunoglobulin nonimmunoglobulin NNP cord-014597-66vd2mdu 904 37 scaffolds scaffold NNS cord-014597-66vd2mdu 904 38 , , , cord-014597-66vd2mdu 904 39 chimeric chimeric JJ cord-014597-66vd2mdu 904 40 antigen antigen NN cord-014597-66vd2mdu 904 41 receptors receptor NNS cord-014597-66vd2mdu 904 42 ( ( -LRB- cord-014597-66vd2mdu 904 43 CARs car NNS cord-014597-66vd2mdu 904 44 ) ) -RRB- cord-014597-66vd2mdu 904 45 , , , cord-014597-66vd2mdu 904 46 engineered engineer VBN cord-014597-66vd2mdu 904 47 T t NN cord-014597-66vd2mdu 904 48 - - HYPH cord-014597-66vd2mdu 904 49 cell cell NN cord-014597-66vd2mdu 904 50 receptors receptor NNS cord-014597-66vd2mdu 904 51 ( ( -LRB- cord-014597-66vd2mdu 904 52 TCRs TCRs NNP cord-014597-66vd2mdu 904 53 ) ) -RRB- cord-014597-66vd2mdu 904 54 and and CC cord-014597-66vd2mdu 904 55 TCR TCR NNP cord-014597-66vd2mdu 904 56 - - HYPH cord-014597-66vd2mdu 904 57 based base VBN cord-014597-66vd2mdu 904 58 bispecific bispecific NN cord-014597-66vd2mdu 904 59 constructs construct NNS cord-014597-66vd2mdu 904 60 can can MD cord-014597-66vd2mdu 904 61 provide provide VB cord-014597-66vd2mdu 904 62 significant significant JJ cord-014597-66vd2mdu 904 63 advantages advantage NNS cord-014597-66vd2mdu 904 64 for for IN cord-014597-66vd2mdu 904 65 use use NN cord-014597-66vd2mdu 904 66 in in IN cord-014597-66vd2mdu 904 67 cancer cancer NN cord-014597-66vd2mdu 904 68 immunotherapy immunotherapy NN cord-014597-66vd2mdu 904 69 . . . cord-014597-66vd2mdu 905 1 However however RB cord-014597-66vd2mdu 905 2 , , , cord-014597-66vd2mdu 905 3 as as IN cord-014597-66vd2mdu 905 4 highly highly RB cord-014597-66vd2mdu 905 5 engineered engineer VBN cord-014597-66vd2mdu 905 6 molecules molecule NNS cord-014597-66vd2mdu 905 7 they -PRON- PRP cord-014597-66vd2mdu 905 8 pose pose VBP cord-014597-66vd2mdu 905 9 new new JJ cord-014597-66vd2mdu 905 10 challenges challenge NNS cord-014597-66vd2mdu 905 11 in in IN cord-014597-66vd2mdu 905 12 design design NN cord-014597-66vd2mdu 905 13 , , , cord-014597-66vd2mdu 905 14 engineering engineering NN cord-014597-66vd2mdu 905 15 , , , cord-014597-66vd2mdu 905 16 cloning cloning NN cord-014597-66vd2mdu 905 17 , , , cord-014597-66vd2mdu 905 18 expression expression NN cord-014597-66vd2mdu 905 19 , , , cord-014597-66vd2mdu 905 20 purification purification NN cord-014597-66vd2mdu 905 21 , , , cord-014597-66vd2mdu 905 22 and and CC cord-014597-66vd2mdu 905 23 analytics analytic NNS cord-014597-66vd2mdu 905 24 . . . cord-014597-66vd2mdu 906 1 We -PRON- PRP cord-014597-66vd2mdu 906 2 have have VBP cord-014597-66vd2mdu 906 3 thus thus RB cord-014597-66vd2mdu 906 4 implemented implement VBN cord-014597-66vd2mdu 906 5 an an DT cord-014597-66vd2mdu 906 6 infrastructure infrastructure NN cord-014597-66vd2mdu 906 7 that that WDT cord-014597-66vd2mdu 906 8 addresses address VBZ cord-014597-66vd2mdu 906 9 these these DT cord-014597-66vd2mdu 906 10 challenges challenge NNS cord-014597-66vd2mdu 906 11 and and CC cord-014597-66vd2mdu 906 12 enables enable VBZ cord-014597-66vd2mdu 906 13 the the DT cord-014597-66vd2mdu 906 14 industrialization industrialization NN cord-014597-66vd2mdu 906 15 of of IN cord-014597-66vd2mdu 906 16 these these DT cord-014597-66vd2mdu 906 17 various various JJ cord-014597-66vd2mdu 906 18 novel novel JJ cord-014597-66vd2mdu 906 19 therapeutic therapeutic JJ cord-014597-66vd2mdu 906 20 platforms platform NNS cord-014597-66vd2mdu 906 21 . . . cord-014597-66vd2mdu 907 1 In in IN cord-014597-66vd2mdu 907 2 close close JJ cord-014597-66vd2mdu 907 3 collaboration collaboration NN cord-014597-66vd2mdu 907 4 with with IN cord-014597-66vd2mdu 907 5 leading lead VBG cord-014597-66vd2mdu 907 6 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 907 7 companies company NNS cord-014597-66vd2mdu 907 8 , , , cord-014597-66vd2mdu 907 9 we -PRON- PRP cord-014597-66vd2mdu 907 10 implemented implement VBD cord-014597-66vd2mdu 907 11 a a DT cord-014597-66vd2mdu 907 12 workflow workflow NN cord-014597-66vd2mdu 907 13 , , , cord-014597-66vd2mdu 907 14 data datum NNS cord-014597-66vd2mdu 907 15 management management NN cord-014597-66vd2mdu 907 16 and and CC cord-014597-66vd2mdu 907 17 analysis analysis NN cord-014597-66vd2mdu 907 18 support support NN cord-014597-66vd2mdu 907 19 system system NN cord-014597-66vd2mdu 907 20 , , , cord-014597-66vd2mdu 907 21 Genedata Genedata NNP cord-014597-66vd2mdu 907 22 Biologics Biologics NNP cord-014597-66vd2mdu 907 23 ™ ™ NN cord-014597-66vd2mdu 907 24 , , , cord-014597-66vd2mdu 907 25 enabling enable VBG cord-014597-66vd2mdu 907 26 the the DT cord-014597-66vd2mdu 907 27 automated automate VBN cord-014597-66vd2mdu 907 28 design design NN cord-014597-66vd2mdu 907 29 , , , cord-014597-66vd2mdu 907 30 screening screening NN cord-014597-66vd2mdu 907 31 , , , cord-014597-66vd2mdu 907 32 and and CC cord-014597-66vd2mdu 907 33 expression expression NN cord-014597-66vd2mdu 907 34 of of IN cord-014597-66vd2mdu 907 35 large large JJ cord-014597-66vd2mdu 907 36 panels panel NNS cord-014597-66vd2mdu 907 37 of of IN cord-014597-66vd2mdu 907 38 therapeutic therapeutic JJ cord-014597-66vd2mdu 907 39 candidates candidate NNS cord-014597-66vd2mdu 907 40 using use VBG cord-014597-66vd2mdu 907 41 these these DT cord-014597-66vd2mdu 907 42 novel novel JJ cord-014597-66vd2mdu 907 43 technologies technology NNS cord-014597-66vd2mdu 907 44 . . . cord-014597-66vd2mdu 908 1 We -PRON- PRP cord-014597-66vd2mdu 908 2 have have VBP cord-014597-66vd2mdu 908 3 also also RB cord-014597-66vd2mdu 908 4 built build VBN cord-014597-66vd2mdu 908 5 tools tool NNS cord-014597-66vd2mdu 908 6 for for IN cord-014597-66vd2mdu 908 7 developability developability NN cord-014597-66vd2mdu 908 8 and and CC cord-014597-66vd2mdu 908 9 manufacturability manufacturability NN cord-014597-66vd2mdu 908 10 assessments assessment NNS cord-014597-66vd2mdu 908 11 of of IN cord-014597-66vd2mdu 908 12 these these DT cord-014597-66vd2mdu 908 13 complex complex JJ cord-014597-66vd2mdu 908 14 molecules molecule NNS cord-014597-66vd2mdu 908 15 . . . cord-014597-66vd2mdu 909 1 We -PRON- PRP cord-014597-66vd2mdu 909 2 have have VBP cord-014597-66vd2mdu 909 3 ensured ensure VBN cord-014597-66vd2mdu 909 4 that that IN cord-014597-66vd2mdu 909 5 there there EX cord-014597-66vd2mdu 909 6 is be VBZ cord-014597-66vd2mdu 909 7 a a DT cord-014597-66vd2mdu 909 8 seamless seamless JJ cord-014597-66vd2mdu 909 9 integration integration NN cord-014597-66vd2mdu 909 10 of of IN cord-014597-66vd2mdu 909 11 all all DT cord-014597-66vd2mdu 909 12 data datum NNS cord-014597-66vd2mdu 909 13 generated generate VBN cord-014597-66vd2mdu 909 14 and and CC cord-014597-66vd2mdu 909 15 that that IN cord-014597-66vd2mdu 909 16 functionalities functionality NNS cord-014597-66vd2mdu 909 17 such such JJ cord-014597-66vd2mdu 909 18 as as IN cord-014597-66vd2mdu 909 19 bulk bulk JJ cord-014597-66vd2mdu 909 20 protein protein NN cord-014597-66vd2mdu 909 21 and and CC cord-014597-66vd2mdu 909 22 vector vector NN cord-014597-66vd2mdu 909 23 generation generation NN cord-014597-66vd2mdu 909 24 using use VBG cord-014597-66vd2mdu 909 25 our -PRON- PRP$ cord-014597-66vd2mdu 909 26 in in IN cord-014597-66vd2mdu 909 27 silico silico NN cord-014597-66vd2mdu 909 28 cloning clone VBG cord-014597-66vd2mdu 909 29 engine engine NN cord-014597-66vd2mdu 909 30 , , , cord-014597-66vd2mdu 909 31 configurable configurable JJ cord-014597-66vd2mdu 909 32 library library NN cord-014597-66vd2mdu 909 33 of of IN cord-014597-66vd2mdu 909 34 template template NN cord-014597-66vd2mdu 909 35 vectors vector NNS cord-014597-66vd2mdu 909 36 and and CC cord-014597-66vd2mdu 909 37 cloning clone VBG cord-014597-66vd2mdu 909 38 strategies strategy NNS cord-014597-66vd2mdu 909 39 , , , cord-014597-66vd2mdu 909 40 fully fully RB cord-014597-66vd2mdu 909 41 annotated annotate VBN cord-014597-66vd2mdu 909 42 in in IN cord-014597-66vd2mdu 909 43 silico silico NN cord-014597-66vd2mdu 909 44 protein protein NN cord-014597-66vd2mdu 909 45 molecules molecule NNS cord-014597-66vd2mdu 909 46 and and CC cord-014597-66vd2mdu 909 47 DNA dna NN cord-014597-66vd2mdu 909 48 constructs construct NNS cord-014597-66vd2mdu 909 49 , , , cord-014597-66vd2mdu 909 50 and and CC cord-014597-66vd2mdu 909 51 DNA dna NN cord-014597-66vd2mdu 909 52 synthesis synthesis NN cord-014597-66vd2mdu 909 53 verification verification NN cord-014597-66vd2mdu 909 54 support support NN cord-014597-66vd2mdu 909 55 , , , cord-014597-66vd2mdu 909 56 can can MD cord-014597-66vd2mdu 909 57 be be VB cord-014597-66vd2mdu 909 58 used use VBN cord-014597-66vd2mdu 909 59 for for IN cord-014597-66vd2mdu 909 60 the the DT cord-014597-66vd2mdu 909 61 newest new JJS cord-014597-66vd2mdu 909 62 protein protein NN cord-014597-66vd2mdu 909 63 formats format NNS cord-014597-66vd2mdu 909 64 and and CC cord-014597-66vd2mdu 909 65 molecule molecule NN cord-014597-66vd2mdu 909 66 topologies topology NNS cord-014597-66vd2mdu 909 67 . . . cord-014597-66vd2mdu 910 1 We -PRON- PRP cord-014597-66vd2mdu 910 2 implemented implement VBD cord-014597-66vd2mdu 910 3 data data NN cord-014597-66vd2mdu 910 4 structures structure NNS cord-014597-66vd2mdu 910 5 and and CC cord-014597-66vd2mdu 910 6 data datum NNS cord-014597-66vd2mdu 910 7 handling handle VBG cord-014597-66vd2mdu 910 8 systems system NNS cord-014597-66vd2mdu 910 9 , , , cord-014597-66vd2mdu 910 10 which which WDT cord-014597-66vd2mdu 910 11 mirror mirror VBP cord-014597-66vd2mdu 910 12 how how WRB cord-014597-66vd2mdu 910 13 these these DT cord-014597-66vd2mdu 910 14 complex complex JJ cord-014597-66vd2mdu 910 15 next next JJ cord-014597-66vd2mdu 910 16 - - HYPH cord-014597-66vd2mdu 910 17 generation generation NN cord-014597-66vd2mdu 910 18 biologics biologic NNS cord-014597-66vd2mdu 910 19 molecules molecule NNS cord-014597-66vd2mdu 910 20 and and CC cord-014597-66vd2mdu 910 21 cell cell NN cord-014597-66vd2mdu 910 22 lines line NNS cord-014597-66vd2mdu 910 23 are be VBP cord-014597-66vd2mdu 910 24 being be VBG cord-014597-66vd2mdu 910 25 designed design VBN cord-014597-66vd2mdu 910 26 , , , cord-014597-66vd2mdu 910 27 screened screen VBN cord-014597-66vd2mdu 910 28 , , , cord-014597-66vd2mdu 910 29 and and CC cord-014597-66vd2mdu 910 30 analyzed analyze VBD cord-014597-66vd2mdu 910 31 . . . cord-014597-66vd2mdu 911 1 The the DT cord-014597-66vd2mdu 911 2 result result NN cord-014597-66vd2mdu 911 3 successfully successfully RB cord-014597-66vd2mdu 911 4 addresses address VBZ cord-014597-66vd2mdu 911 5 workflows workflow NNS cord-014597-66vd2mdu 911 6 for for IN cord-014597-66vd2mdu 911 7 TCR TCR NNP cord-014597-66vd2mdu 911 8 optimization optimization NN cord-014597-66vd2mdu 911 9 and and CC cord-014597-66vd2mdu 911 10 engineering engineering NN cord-014597-66vd2mdu 911 11 . . . cord-014597-66vd2mdu 912 1 We -PRON- PRP cord-014597-66vd2mdu 912 2 exemplified exemplify VBD cord-014597-66vd2mdu 912 3 this this DT cord-014597-66vd2mdu 912 4 with with IN cord-014597-66vd2mdu 912 5 the the DT cord-014597-66vd2mdu 912 6 generation generation NN cord-014597-66vd2mdu 912 7 and and CC cord-014597-66vd2mdu 912 8 evaluation evaluation NN cord-014597-66vd2mdu 912 9 of of IN cord-014597-66vd2mdu 912 10 a a DT cord-014597-66vd2mdu 912 11 panel panel NN cord-014597-66vd2mdu 912 12 of of IN cord-014597-66vd2mdu 912 13 engineered engineer VBN cord-014597-66vd2mdu 912 14 TCRs tcr NNS cord-014597-66vd2mdu 912 15 with with IN cord-014597-66vd2mdu 912 16 an an DT cord-014597-66vd2mdu 912 17 alpha alpha NN cord-014597-66vd2mdu 912 18 chain chain NN cord-014597-66vd2mdu 912 19 CDR3 CDR3 NNP cord-014597-66vd2mdu 912 20 randomization randomization NN cord-014597-66vd2mdu 912 21 and and CC cord-014597-66vd2mdu 912 22 successfully successfully RB cord-014597-66vd2mdu 912 23 supported support VBD cord-014597-66vd2mdu 912 24 the the DT cord-014597-66vd2mdu 912 25 analysis analysis NN cord-014597-66vd2mdu 912 26 and and CC cord-014597-66vd2mdu 912 27 selection selection NN cord-014597-66vd2mdu 912 28 of of IN cord-014597-66vd2mdu 912 29 beneficial beneficial JJ cord-014597-66vd2mdu 912 30 mutations mutation NNS cord-014597-66vd2mdu 912 31 . . . cord-014597-66vd2mdu 913 1 The the DT cord-014597-66vd2mdu 913 2 system system NN cord-014597-66vd2mdu 913 3 also also RB cord-014597-66vd2mdu 913 4 successfully successfully RB cord-014597-66vd2mdu 913 5 supported support VBD cord-014597-66vd2mdu 913 6 workflows workflow NNS cord-014597-66vd2mdu 913 7 for for IN cord-014597-66vd2mdu 913 8 the the DT cord-014597-66vd2mdu 913 9 design design NN cord-014597-66vd2mdu 913 10 and and CC cord-014597-66vd2mdu 913 11 generation generation NN cord-014597-66vd2mdu 913 12 of of IN cord-014597-66vd2mdu 913 13 a a DT cord-014597-66vd2mdu 913 14 panel panel NN cord-014597-66vd2mdu 913 15 of of IN cord-014597-66vd2mdu 913 16 TCR TCR NNP cord-014597-66vd2mdu 913 17 - - HYPH cord-014597-66vd2mdu 913 18 based base VBN cord-014597-66vd2mdu 913 19 bispecifics bispecific NNS cord-014597-66vd2mdu 914 1 ( ( -LRB- cord-014597-66vd2mdu 914 2 TCR TCR NNP cord-014597-66vd2mdu 914 3 coupled couple VBD cord-014597-66vd2mdu 914 4 with with IN cord-014597-66vd2mdu 914 5 anti anti JJ cord-014597-66vd2mdu 914 6 - - JJ cord-014597-66vd2mdu 914 7 CD3 cd3 JJ cord-014597-66vd2mdu 914 8 ) ) -RRB- cord-014597-66vd2mdu 914 9 using use VBG cord-014597-66vd2mdu 914 10 automated automate VBN cord-014597-66vd2mdu 914 11 molecule molecule NN cord-014597-66vd2mdu 914 12 registration registration NN cord-014597-66vd2mdu 914 13 and and CC cord-014597-66vd2mdu 914 14 in in IN cord-014597-66vd2mdu 914 15 silico silico NN cord-014597-66vd2mdu 914 16 cloning cloning NN cord-014597-66vd2mdu 914 17 tools tool NNS cord-014597-66vd2mdu 914 18 and and CC cord-014597-66vd2mdu 914 19 subsequent subsequent JJ cord-014597-66vd2mdu 914 20 capture capture NN cord-014597-66vd2mdu 914 21 of of IN cord-014597-66vd2mdu 914 22 expression expression NN cord-014597-66vd2mdu 914 23 , , , cord-014597-66vd2mdu 914 24 purification purification NN cord-014597-66vd2mdu 914 25 , , , cord-014597-66vd2mdu 914 26 and and CC cord-014597-66vd2mdu 914 27 functional functional JJ cord-014597-66vd2mdu 914 28 and and CC cord-014597-66vd2mdu 914 29 analytical analytical JJ cord-014597-66vd2mdu 914 30 characterization characterization NN cord-014597-66vd2mdu 914 31 data datum NNS cord-014597-66vd2mdu 914 32 . . . cord-014597-66vd2mdu 915 1 On on IN cord-014597-66vd2mdu 915 2 the the DT cord-014597-66vd2mdu 915 3 CAR car NN cord-014597-66vd2mdu 915 4 - - HYPH cord-014597-66vd2mdu 915 5 T t NN cord-014597-66vd2mdu 915 6 cell cell NN cord-014597-66vd2mdu 915 7 front front NN cord-014597-66vd2mdu 915 8 , , , cord-014597-66vd2mdu 915 9 the the DT cord-014597-66vd2mdu 915 10 system system NN cord-014597-66vd2mdu 915 11 is be VBZ cord-014597-66vd2mdu 915 12 able able JJ cord-014597-66vd2mdu 915 13 to to TO cord-014597-66vd2mdu 915 14 provide provide VB cord-014597-66vd2mdu 915 15 traceability traceability NN cord-014597-66vd2mdu 915 16 of of IN cord-014597-66vd2mdu 915 17 the the DT cord-014597-66vd2mdu 915 18 work work NN cord-014597-66vd2mdu 915 19 from from IN cord-014597-66vd2mdu 915 20 antibody antibody NN cord-014597-66vd2mdu 915 21 generation generation NN cord-014597-66vd2mdu 915 22 , , , cord-014597-66vd2mdu 915 23 optimization optimization NN cord-014597-66vd2mdu 915 24 , , , cord-014597-66vd2mdu 915 25 CAR car NN cord-014597-66vd2mdu 915 26 engineering engineering NN cord-014597-66vd2mdu 915 27 ( ( -LRB- cord-014597-66vd2mdu 915 28 e.g. e.g. RB cord-014597-66vd2mdu 915 29 , , , cord-014597-66vd2mdu 915 30 attachment attachment NN cord-014597-66vd2mdu 915 31 to to IN cord-014597-66vd2mdu 915 32 the the DT cord-014597-66vd2mdu 915 33 scFv scFv NNS cord-014597-66vd2mdu 915 34 with with IN cord-014597-66vd2mdu 915 35 CD3-zeta cd3-zeta NN cord-014597-66vd2mdu 915 36 and and CC cord-014597-66vd2mdu 915 37 co co JJ cord-014597-66vd2mdu 915 38 - - JJ cord-014597-66vd2mdu 915 39 stimulatory stimulatory JJ cord-014597-66vd2mdu 915 40 domains domain NNS cord-014597-66vd2mdu 915 41 to to TO cord-014597-66vd2mdu 915 42 mimic mimic VB cord-014597-66vd2mdu 915 43 the the DT cord-014597-66vd2mdu 915 44 natural natural JJ cord-014597-66vd2mdu 915 45 TCR TCR NNP cord-014597-66vd2mdu 915 46 complex complex NN cord-014597-66vd2mdu 915 47 ) ) -RRB- cord-014597-66vd2mdu 915 48 to to IN cord-014597-66vd2mdu 915 49 the the DT cord-014597-66vd2mdu 915 50 engineering engineering NN cord-014597-66vd2mdu 915 51 of of IN cord-014597-66vd2mdu 915 52 the the DT cord-014597-66vd2mdu 915 53 T t NN cord-014597-66vd2mdu 915 54 - - HYPH cord-014597-66vd2mdu 915 55 cell cell NN cord-014597-66vd2mdu 915 56 . . . cord-014597-66vd2mdu 916 1 The the DT cord-014597-66vd2mdu 916 2 Genedata Genedata NNP cord-014597-66vd2mdu 916 3 Biologics Biologics NNP cord-014597-66vd2mdu 916 4 platform platform NN cord-014597-66vd2mdu 916 5 successfully successfully RB cord-014597-66vd2mdu 916 6 enabled enable VBD cord-014597-66vd2mdu 916 7 automation automation NN cord-014597-66vd2mdu 916 8 , , , cord-014597-66vd2mdu 916 9 increased increase VBN cord-014597-66vd2mdu 916 10 data datum NNS cord-014597-66vd2mdu 916 11 integrity integrity NN cord-014597-66vd2mdu 916 12 and and CC cord-014597-66vd2mdu 916 13 traceability traceability NN cord-014597-66vd2mdu 916 14 during during IN cord-014597-66vd2mdu 916 15 research research NN cord-014597-66vd2mdu 916 16 and and CC cord-014597-66vd2mdu 916 17 development development NN cord-014597-66vd2mdu 916 18 work work NN cord-014597-66vd2mdu 916 19 , , , cord-014597-66vd2mdu 916 20 and and CC cord-014597-66vd2mdu 916 21 will will MD cord-014597-66vd2mdu 916 22 contribute contribute VB cord-014597-66vd2mdu 916 23 towards towards IN cord-014597-66vd2mdu 916 24 the the DT cord-014597-66vd2mdu 916 25 industrialization industrialization NN cord-014597-66vd2mdu 916 26 of of IN cord-014597-66vd2mdu 916 27 these these DT cord-014597-66vd2mdu 916 28 very very RB cord-014597-66vd2mdu 916 29 exciting exciting JJ cord-014597-66vd2mdu 916 30 novel novel JJ cord-014597-66vd2mdu 916 31 approaches approach NNS cord-014597-66vd2mdu 916 32 for for IN cord-014597-66vd2mdu 916 33 cancer cancer NN cord-014597-66vd2mdu 916 34 immunotherapy immunotherapy NN cord-014597-66vd2mdu 916 35 . . . cord-014597-66vd2mdu 917 1 Optimal optimal JJ cord-014597-66vd2mdu 917 2 selection selection NN cord-014597-66vd2mdu 917 3 of of IN cord-014597-66vd2mdu 917 4 therapeutic therapeutic JJ cord-014597-66vd2mdu 917 5 antibodies antibody NNS cord-014597-66vd2mdu 917 6 and and CC cord-014597-66vd2mdu 917 7 production production NN cord-014597-66vd2mdu 917 8 cell cell NN cord-014597-66vd2mdu 917 9 lines line NNS cord-014597-66vd2mdu 917 10 by by IN cord-014597-66vd2mdu 917 11 assessment assessment NN cord-014597-66vd2mdu 917 12 of of IN cord-014597-66vd2mdu 917 13 critical critical JJ cord-014597-66vd2mdu 917 14 quality quality NN cord-014597-66vd2mdu 917 15 attributes attribute NNS cord-014597-66vd2mdu 917 16 and and CC cord-014597-66vd2mdu 917 17 developability developability NN cord-014597-66vd2mdu 917 18 Background background NN cord-014597-66vd2mdu 918 1 The the DT cord-014597-66vd2mdu 918 2 increasing increase VBG cord-014597-66vd2mdu 918 3 cost cost NN cord-014597-66vd2mdu 918 4 of of IN cord-014597-66vd2mdu 918 5 bringing bring VBG cord-014597-66vd2mdu 918 6 a a DT cord-014597-66vd2mdu 918 7 new new JJ cord-014597-66vd2mdu 918 8 drug drug NN cord-014597-66vd2mdu 918 9 to to IN cord-014597-66vd2mdu 918 10 the the DT cord-014597-66vd2mdu 918 11 market market NN cord-014597-66vd2mdu 918 12 has have VBZ cord-014597-66vd2mdu 918 13 put put VBN cord-014597-66vd2mdu 918 14 significant significant JJ cord-014597-66vd2mdu 918 15 pressure pressure NN cord-014597-66vd2mdu 918 16 on on IN cord-014597-66vd2mdu 918 17 biopharma biopharma NN cord-014597-66vd2mdu 918 18 organizations organization NNS cord-014597-66vd2mdu 918 19 . . . cord-014597-66vd2mdu 919 1 To to TO cord-014597-66vd2mdu 919 2 increase increase VB cord-014597-66vd2mdu 919 3 efficiency efficiency NN cord-014597-66vd2mdu 919 4 in in IN cord-014597-66vd2mdu 919 5 R&D r&d NN cord-014597-66vd2mdu 919 6 processes process NNS cord-014597-66vd2mdu 919 7 and and CC cord-014597-66vd2mdu 919 8 reduce reduce VB cord-014597-66vd2mdu 919 9 costs cost NNS cord-014597-66vd2mdu 919 10 , , , cord-014597-66vd2mdu 919 11 organizations organization NNS cord-014597-66vd2mdu 919 12 need need VBP cord-014597-66vd2mdu 919 13 to to TO cord-014597-66vd2mdu 919 14 evaluate evaluate VB cord-014597-66vd2mdu 919 15 potential potential JJ cord-014597-66vd2mdu 919 16 drug drug NN cord-014597-66vd2mdu 919 17 candidates candidate NNS cord-014597-66vd2mdu 919 18 earlier early RBR cord-014597-66vd2mdu 919 19 in in IN cord-014597-66vd2mdu 919 20 the the DT cord-014597-66vd2mdu 919 21 R&D r&d NN cord-014597-66vd2mdu 919 22 process process NN cord-014597-66vd2mdu 919 23 , , , cord-014597-66vd2mdu 919 24 eliminate eliminate VB cord-014597-66vd2mdu 919 25 those those DT cord-014597-66vd2mdu 919 26 with with IN cord-014597-66vd2mdu 919 27 undesirable undesirable JJ cord-014597-66vd2mdu 919 28 characteristics characteristic NNS cord-014597-66vd2mdu 919 29 , , , cord-014597-66vd2mdu 919 30 and and CC cord-014597-66vd2mdu 919 31 focus focus VB cord-014597-66vd2mdu 919 32 on on IN cord-014597-66vd2mdu 919 33 the the DT cord-014597-66vd2mdu 919 34 most most RBS cord-014597-66vd2mdu 919 35 promising promising JJ cord-014597-66vd2mdu 919 36 candidates candidate NNS cord-014597-66vd2mdu 919 37 . . . cord-014597-66vd2mdu 920 1 After after IN cord-014597-66vd2mdu 920 2 designing design VBG cord-014597-66vd2mdu 920 3 and and CC cord-014597-66vd2mdu 920 4 thorough thorough JJ cord-014597-66vd2mdu 920 5 testing testing NN cord-014597-66vd2mdu 920 6 of of IN cord-014597-66vd2mdu 920 7 successful successful JJ cord-014597-66vd2mdu 920 8 candidates candidate NNS cord-014597-66vd2mdu 920 9 , , , cord-014597-66vd2mdu 920 10 efficient efficient JJ cord-014597-66vd2mdu 920 11 production production NN cord-014597-66vd2mdu 920 12 of of IN cord-014597-66vd2mdu 920 13 new new JJ cord-014597-66vd2mdu 920 14 biological biological JJ cord-014597-66vd2mdu 920 15 entities entity NNS cord-014597-66vd2mdu 920 16 in in IN cord-014597-66vd2mdu 920 17 mammalian mammalian JJ cord-014597-66vd2mdu 920 18 cell cell NN cord-014597-66vd2mdu 920 19 lines line NNS cord-014597-66vd2mdu 920 20 is be VBZ cord-014597-66vd2mdu 920 21 necessary necessary JJ cord-014597-66vd2mdu 920 22 . . . cord-014597-66vd2mdu 921 1 The the DT cord-014597-66vd2mdu 921 2 main main JJ cord-014597-66vd2mdu 921 3 goal goal NN cord-014597-66vd2mdu 921 4 here here RB cord-014597-66vd2mdu 921 5 is be VBZ cord-014597-66vd2mdu 921 6 to to TO cord-014597-66vd2mdu 921 7 find find VB cord-014597-66vd2mdu 921 8 a a DT cord-014597-66vd2mdu 921 9 suitable suitable JJ cord-014597-66vd2mdu 921 10 cell cell NN cord-014597-66vd2mdu 921 11 line line NN cord-014597-66vd2mdu 921 12 and and CC cord-014597-66vd2mdu 921 13 optimal optimal JJ cord-014597-66vd2mdu 921 14 upstream upstream RB cord-014597-66vd2mdu 921 15 and and CC cord-014597-66vd2mdu 921 16 downstream downstream JJ cord-014597-66vd2mdu 921 17 processing processing NN cord-014597-66vd2mdu 921 18 conditions condition NNS cord-014597-66vd2mdu 921 19 that that WDT cord-014597-66vd2mdu 921 20 not not RB cord-014597-66vd2mdu 921 21 only only RB cord-014597-66vd2mdu 921 22 lead lead VB cord-014597-66vd2mdu 921 23 to to IN cord-014597-66vd2mdu 921 24 a a DT cord-014597-66vd2mdu 921 25 satisfactory satisfactory JJ cord-014597-66vd2mdu 921 26 product product NN cord-014597-66vd2mdu 921 27 yield yield NN cord-014597-66vd2mdu 921 28 , , , cord-014597-66vd2mdu 921 29 but but CC cord-014597-66vd2mdu 921 30 also also RB cord-014597-66vd2mdu 921 31 to to IN cord-014597-66vd2mdu 921 32 a a DT cord-014597-66vd2mdu 921 33 product product NN cord-014597-66vd2mdu 921 34 with with IN cord-014597-66vd2mdu 921 35 the the DT cord-014597-66vd2mdu 921 36 desired desire VBN cord-014597-66vd2mdu 921 37 biochemical biochemical JJ cord-014597-66vd2mdu 921 38 properties property NNS cord-014597-66vd2mdu 921 39 . . . cord-014597-66vd2mdu 922 1 The the DT cord-014597-66vd2mdu 922 2 evaluation evaluation NN cord-014597-66vd2mdu 922 3 of of IN cord-014597-66vd2mdu 922 4 production production NN cord-014597-66vd2mdu 922 5 cell cell NN cord-014597-66vd2mdu 922 6 lines line NNS cord-014597-66vd2mdu 922 7 , , , cord-014597-66vd2mdu 922 8 processes process NNS cord-014597-66vd2mdu 922 9 , , , cord-014597-66vd2mdu 922 10 and and CC cord-014597-66vd2mdu 922 11 product product NN cord-014597-66vd2mdu 922 12 quality quality NN cord-014597-66vd2mdu 922 13 attributes attribute NNS cord-014597-66vd2mdu 922 14 is be VBZ cord-014597-66vd2mdu 922 15 performed perform VBN cord-014597-66vd2mdu 922 16 earlier early RBR cord-014597-66vd2mdu 922 17 and and CC cord-014597-66vd2mdu 922 18 in in IN cord-014597-66vd2mdu 922 19 higher high JJR cord-014597-66vd2mdu 922 20 throughput throughput NN cord-014597-66vd2mdu 922 21 for for IN cord-014597-66vd2mdu 922 22 an an DT cord-014597-66vd2mdu 922 23 increasing increase VBG cord-014597-66vd2mdu 922 24 number number NN cord-014597-66vd2mdu 922 25 of of IN cord-014597-66vd2mdu 922 26 drug drug NN cord-014597-66vd2mdu 922 27 candidates candidate NNS cord-014597-66vd2mdu 922 28 . . . cord-014597-66vd2mdu 923 1 In in IN cord-014597-66vd2mdu 923 2 addition addition NN cord-014597-66vd2mdu 923 3 , , , cord-014597-66vd2mdu 923 4 new new JJ cord-014597-66vd2mdu 923 5 methods method NNS cord-014597-66vd2mdu 923 6 in in IN cord-014597-66vd2mdu 923 7 molecular molecular JJ cord-014597-66vd2mdu 923 8 and and CC cord-014597-66vd2mdu 923 9 cell cell NN cord-014597-66vd2mdu 923 10 biology biology NN cord-014597-66vd2mdu 923 11 ( ( -LRB- cord-014597-66vd2mdu 923 12 e.g. e.g. RB cord-014597-66vd2mdu 923 13 , , , cord-014597-66vd2mdu 923 14 novel novel JJ cord-014597-66vd2mdu 923 15 genome genome NN cord-014597-66vd2mdu 923 16 engineering engineering NN cord-014597-66vd2mdu 923 17 approaches approach NNS cord-014597-66vd2mdu 923 18 such such JJ cord-014597-66vd2mdu 923 19 as as IN cord-014597-66vd2mdu 923 20 CRISPR CRISPR NNP cord-014597-66vd2mdu 923 21 / / SYM cord-014597-66vd2mdu 923 22 Cas9 Cas9 NNP cord-014597-66vd2mdu 923 23 ) ) -RRB- cord-014597-66vd2mdu 923 24 , , , cord-014597-66vd2mdu 923 25 in in IN cord-014597-66vd2mdu 923 26 analytics analytic NNS cord-014597-66vd2mdu 923 27 [ [ -LRB- cord-014597-66vd2mdu 923 28 e.g. e.g. RB cord-014597-66vd2mdu 923 29 , , , cord-014597-66vd2mdu 923 30 Process Process NNP cord-014597-66vd2mdu 923 31 Analytical Analytical NNP cord-014597-66vd2mdu 923 32 Techniques Techniques NNPS cord-014597-66vd2mdu 923 33 ( ( -LRB- cord-014597-66vd2mdu 923 34 PATs PATs NNP cord-014597-66vd2mdu 923 35 ) ) -RRB- cord-014597-66vd2mdu 923 36 ] ] -RRB- cord-014597-66vd2mdu 923 37 , , , cord-014597-66vd2mdu 923 38 in in IN cord-014597-66vd2mdu 923 39 process process NN cord-014597-66vd2mdu 923 40 miniaturization miniaturization NN cord-014597-66vd2mdu 923 41 , , , cord-014597-66vd2mdu 923 42 and and CC cord-014597-66vd2mdu 923 43 in in IN cord-014597-66vd2mdu 923 44 automation automation NN cord-014597-66vd2mdu 923 45 promise promise NN cord-014597-66vd2mdu 923 46 to to TO cord-014597-66vd2mdu 923 47 make make VB cord-014597-66vd2mdu 923 48 process process NN cord-014597-66vd2mdu 923 49 development development NN cord-014597-66vd2mdu 923 50 more more RBR cord-014597-66vd2mdu 923 51 efficient efficient JJ cord-014597-66vd2mdu 923 52 . . . cord-014597-66vd2mdu 924 1 However however RB cord-014597-66vd2mdu 924 2 , , , cord-014597-66vd2mdu 924 3 the the DT cord-014597-66vd2mdu 924 4 management management NN cord-014597-66vd2mdu 924 5 and and CC cord-014597-66vd2mdu 924 6 analysis analysis NN cord-014597-66vd2mdu 924 7 of of IN cord-014597-66vd2mdu 924 8 the the DT cord-014597-66vd2mdu 924 9 increasing increase VBG cord-014597-66vd2mdu 924 10 amount amount NN cord-014597-66vd2mdu 924 11 of of IN cord-014597-66vd2mdu 924 12 experimental experimental JJ cord-014597-66vd2mdu 924 13 data datum NNS cord-014597-66vd2mdu 924 14 during during IN cord-014597-66vd2mdu 924 15 candidate candidate NN cord-014597-66vd2mdu 924 16 selection selection NN cord-014597-66vd2mdu 924 17 and and CC cord-014597-66vd2mdu 924 18 cell cell NN cord-014597-66vd2mdu 924 19 line line NN cord-014597-66vd2mdu 924 20 and and CC cord-014597-66vd2mdu 924 21 process process NN cord-014597-66vd2mdu 924 22 development development NN cord-014597-66vd2mdu 924 23 has have VBZ cord-014597-66vd2mdu 924 24 become become VBN cord-014597-66vd2mdu 924 25 a a DT cord-014597-66vd2mdu 924 26 bottleneck bottleneck NN cord-014597-66vd2mdu 924 27 . . . cord-014597-66vd2mdu 925 1 In in IN cord-014597-66vd2mdu 925 2 addition addition NN cord-014597-66vd2mdu 925 3 , , , cord-014597-66vd2mdu 925 4 quality quality NN cord-014597-66vd2mdu 925 5 - - HYPH cord-014597-66vd2mdu 925 6 compromising compromise VBG cord-014597-66vd2mdu 925 7 steps step NNS cord-014597-66vd2mdu 925 8 in in IN cord-014597-66vd2mdu 925 9 biopharma biopharma NN cord-014597-66vd2mdu 925 10 organizations organization NNS cord-014597-66vd2mdu 925 11 can can MD cord-014597-66vd2mdu 925 12 negatively negatively RB cord-014597-66vd2mdu 925 13 impact impact VB cord-014597-66vd2mdu 925 14 the the DT cord-014597-66vd2mdu 925 15 cost cost NN cord-014597-66vd2mdu 925 16 of of IN cord-014597-66vd2mdu 925 17 goods good NNS cord-014597-66vd2mdu 925 18 and and CC cord-014597-66vd2mdu 925 19 substantially substantially RB cord-014597-66vd2mdu 925 20 prolong prolong VB cord-014597-66vd2mdu 925 21 the the DT cord-014597-66vd2mdu 925 22 drug drug NN cord-014597-66vd2mdu 925 23 candidate candidate NN cord-014597-66vd2mdu 925 24 's 's POS cord-014597-66vd2mdu 925 25 time time NN cord-014597-66vd2mdu 925 26 to to IN cord-014597-66vd2mdu 925 27 market market NN cord-014597-66vd2mdu 925 28 . . . cord-014597-66vd2mdu 926 1 Therefore therefore RB cord-014597-66vd2mdu 926 2 , , , cord-014597-66vd2mdu 926 3 systems system NNS cord-014597-66vd2mdu 926 4 for for IN cord-014597-66vd2mdu 926 5 integrated integrated JJ cord-014597-66vd2mdu 926 6 management management NN cord-014597-66vd2mdu 926 7 and and CC cord-014597-66vd2mdu 926 8 analysis analysis NN cord-014597-66vd2mdu 926 9 of of IN cord-014597-66vd2mdu 926 10 wellstructured wellstructured NNP cord-014597-66vd2mdu 926 11 and and CC cord-014597-66vd2mdu 926 12 curated curate VBN cord-014597-66vd2mdu 926 13 data datum NNS cord-014597-66vd2mdu 926 14 that that WDT cord-014597-66vd2mdu 926 15 comprehensively comprehensively RB cord-014597-66vd2mdu 926 16 integrate integrate VBP cord-014597-66vd2mdu 926 17 molecule molecule NN cord-014597-66vd2mdu 926 18 and and CC cord-014597-66vd2mdu 926 19 sample sample NN cord-014597-66vd2mdu 926 20 information information NN cord-014597-66vd2mdu 926 21 , , , cord-014597-66vd2mdu 926 22 manufacturing manufacturing NN cord-014597-66vd2mdu 926 23 process process NN cord-014597-66vd2mdu 926 24 parameters parameter NNS cord-014597-66vd2mdu 926 25 , , , cord-014597-66vd2mdu 926 26 and and CC cord-014597-66vd2mdu 926 27 process process NN cord-014597-66vd2mdu 926 28 and and CC cord-014597-66vd2mdu 926 29 product product NN cord-014597-66vd2mdu 926 30 quality quality NN cord-014597-66vd2mdu 926 31 attributes attribute NNS cord-014597-66vd2mdu 926 32 are be VBP cord-014597-66vd2mdu 926 33 needed need VBN cord-014597-66vd2mdu 926 34 . . . cord-014597-66vd2mdu 927 1 Critical critical JJ cord-014597-66vd2mdu 927 2 quality quality NN cord-014597-66vd2mdu 927 3 attribute attribute NN cord-014597-66vd2mdu 927 4 ( ( -LRB- cord-014597-66vd2mdu 927 5 CQA CQA NNP cord-014597-66vd2mdu 927 6 ) ) -RRB- cord-014597-66vd2mdu 927 7 assessment assessment NN cord-014597-66vd2mdu 927 8 should should MD cord-014597-66vd2mdu 927 9 be be VB cord-014597-66vd2mdu 927 10 enabled enable VBN cord-014597-66vd2mdu 927 11 along along IN cord-014597-66vd2mdu 927 12 the the DT cord-014597-66vd2mdu 927 13 whole whole JJ cord-014597-66vd2mdu 927 14 bioprocess bioprocess NNP cord-014597-66vd2mdu 927 15 development development NNP cord-014597-66vd2mdu 927 16 workflow workflow NN cord-014597-66vd2mdu 927 17 , , , cord-014597-66vd2mdu 927 18 including include VBG cord-014597-66vd2mdu 927 19 cell cell NN cord-014597-66vd2mdu 927 20 line line NN cord-014597-66vd2mdu 927 21 development development NN cord-014597-66vd2mdu 927 22 , , , cord-014597-66vd2mdu 927 23 upstream upstream JJ cord-014597-66vd2mdu 927 24 and and CC cord-014597-66vd2mdu 927 25 downstream downstream JJ cord-014597-66vd2mdu 927 26 process process NN cord-014597-66vd2mdu 927 27 development development NN cord-014597-66vd2mdu 927 28 , , , cord-014597-66vd2mdu 927 29 as as RB cord-014597-66vd2mdu 927 30 well well RB cord-014597-66vd2mdu 927 31 as as IN cord-014597-66vd2mdu 927 32 analytical analytical JJ cord-014597-66vd2mdu 927 33 and and CC cord-014597-66vd2mdu 927 34 formulation formulation NN cord-014597-66vd2mdu 927 35 development development NN cord-014597-66vd2mdu 927 36 . . . cord-014597-66vd2mdu 928 1 We -PRON- PRP cord-014597-66vd2mdu 928 2 have have VBP cord-014597-66vd2mdu 928 3 developed develop VBN cord-014597-66vd2mdu 928 4 a a DT cord-014597-66vd2mdu 928 5 comprehensive comprehensive JJ cord-014597-66vd2mdu 928 6 platform platform NN cord-014597-66vd2mdu 928 7 , , , cord-014597-66vd2mdu 928 8 Genedata Genedata NNP cord-014597-66vd2mdu 928 9 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 928 10 ™ ™ NN cord-014597-66vd2mdu 928 11 , , , cord-014597-66vd2mdu 928 12 which which WDT cord-014597-66vd2mdu 928 13 supports support VBZ cord-014597-66vd2mdu 928 14 drug drug NN cord-014597-66vd2mdu 928 15 candidate candidate NN cord-014597-66vd2mdu 928 16 developability developability NN cord-014597-66vd2mdu 928 17 and and CC cord-014597-66vd2mdu 928 18 manufacturability manufacturability NN cord-014597-66vd2mdu 928 19 assessment assessment NN cord-014597-66vd2mdu 928 20 and and CC cord-014597-66vd2mdu 928 21 bioprocess bioprocess NN cord-014597-66vd2mdu 928 22 development development NN cord-014597-66vd2mdu 928 23 . . . cord-014597-66vd2mdu 929 1 The the DT cord-014597-66vd2mdu 929 2 platform platform NN cord-014597-66vd2mdu 929 3 captures capture VBZ cord-014597-66vd2mdu 929 4 and and CC cord-014597-66vd2mdu 929 5 structures structure NNS cord-014597-66vd2mdu 929 6 the the DT cord-014597-66vd2mdu 929 7 cell cell NN cord-014597-66vd2mdu 929 8 line line NN cord-014597-66vd2mdu 929 9 and and CC cord-014597-66vd2mdu 929 10 process process NN cord-014597-66vd2mdu 929 11 parameters parameter NNS cord-014597-66vd2mdu 929 12 together together RB cord-014597-66vd2mdu 929 13 with with IN cord-014597-66vd2mdu 929 14 analytical analytical JJ cord-014597-66vd2mdu 929 15 data datum NNS cord-014597-66vd2mdu 929 16 for for IN cord-014597-66vd2mdu 929 17 cell cell NN cord-014597-66vd2mdu 929 18 lines line NNS cord-014597-66vd2mdu 929 19 , , , cord-014597-66vd2mdu 929 20 processes process NNS cord-014597-66vd2mdu 929 21 , , , cord-014597-66vd2mdu 929 22 and and CC cord-014597-66vd2mdu 929 23 protein protein NN cord-014597-66vd2mdu 929 24 products product NNS cord-014597-66vd2mdu 929 25 . . . cord-014597-66vd2mdu 930 1 The the DT cord-014597-66vd2mdu 930 2 protein protein NN cord-014597-66vd2mdu 930 3 analytical analytical JJ cord-014597-66vd2mdu 930 4 data datum NNS cord-014597-66vd2mdu 930 5 being be VBG cord-014597-66vd2mdu 930 6 tracked track VBN cord-014597-66vd2mdu 930 7 include include VBP cord-014597-66vd2mdu 930 8 biological biological JJ cord-014597-66vd2mdu 930 9 data datum NNS cord-014597-66vd2mdu 930 10 ( ( -LRB- cord-014597-66vd2mdu 930 11 such such JJ cord-014597-66vd2mdu 930 12 as as IN cord-014597-66vd2mdu 930 13 bioactivity bioactivity NN cord-014597-66vd2mdu 930 14 , , , cord-014597-66vd2mdu 930 15 immunogenicity immunogenicity NN cord-014597-66vd2mdu 930 16 ) ) -RRB- cord-014597-66vd2mdu 930 17 , , , cord-014597-66vd2mdu 930 18 and and CC cord-014597-66vd2mdu 930 19 physicochemical physicochemical JJ cord-014597-66vd2mdu 930 20 properties property NNS cord-014597-66vd2mdu 930 21 . . . cord-014597-66vd2mdu 931 1 These these DT cord-014597-66vd2mdu 931 2 properties property NNS cord-014597-66vd2mdu 931 3 include include VBP cord-014597-66vd2mdu 931 4 glycosylation glycosylation NN cord-014597-66vd2mdu 931 5 , , , cord-014597-66vd2mdu 931 6 chemical chemical NN cord-014597-66vd2mdu 931 7 liabilities liability NNS cord-014597-66vd2mdu 931 8 ( ( -LRB- cord-014597-66vd2mdu 931 9 such such JJ cord-014597-66vd2mdu 931 10 as as IN cord-014597-66vd2mdu 931 11 deamidation deamidation NN cord-014597-66vd2mdu 931 12 and and CC cord-014597-66vd2mdu 931 13 oxidation oxidation NN cord-014597-66vd2mdu 931 14 ) ) -RRB- cord-014597-66vd2mdu 931 15 , , , cord-014597-66vd2mdu 931 16 aggregation aggregation NN cord-014597-66vd2mdu 931 17 , , , cord-014597-66vd2mdu 931 18 stability stability NN cord-014597-66vd2mdu 931 19 under under IN cord-014597-66vd2mdu 931 20 different different JJ cord-014597-66vd2mdu 931 21 conditions condition NNS cord-014597-66vd2mdu 931 22 ( ( -LRB- cord-014597-66vd2mdu 931 23 low low JJ cord-014597-66vd2mdu 931 24 pH ph NN cord-014597-66vd2mdu 931 25 , , , cord-014597-66vd2mdu 931 26 low low JJ cord-014597-66vd2mdu 931 27 and and CC cord-014597-66vd2mdu 931 28 high high JJ cord-014597-66vd2mdu 931 29 temperature temperature NN cord-014597-66vd2mdu 931 30 ) ) -RRB- cord-014597-66vd2mdu 931 31 , , , cord-014597-66vd2mdu 931 32 solubility solubility NN cord-014597-66vd2mdu 931 33 , , , cord-014597-66vd2mdu 931 34 and and CC cord-014597-66vd2mdu 931 35 impurities impurity NNS cord-014597-66vd2mdu 931 36 . . . cord-014597-66vd2mdu 932 1 Genedata Genedata NNP cord-014597-66vd2mdu 932 2 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 932 3 ™ ™ NN cord-014597-66vd2mdu 932 4 simplifies simplify VBZ cord-014597-66vd2mdu 932 5 and and CC cord-014597-66vd2mdu 932 6 streamlines streamline VBZ cord-014597-66vd2mdu 932 7 laborious laborious JJ cord-014597-66vd2mdu 932 8 , , , cord-014597-66vd2mdu 932 9 manual manual JJ cord-014597-66vd2mdu 932 10 process process NN cord-014597-66vd2mdu 932 11 and and CC cord-014597-66vd2mdu 932 12 supports support VBZ cord-014597-66vd2mdu 932 13 tools tool NNS cord-014597-66vd2mdu 932 14 for for IN cord-014597-66vd2mdu 932 15 molecule molecule NN cord-014597-66vd2mdu 932 16 , , , cord-014597-66vd2mdu 932 17 clone clone NN cord-014597-66vd2mdu 932 18 and and CC cord-014597-66vd2mdu 932 19 process process NN cord-014597-66vd2mdu 932 20 selection selection NN cord-014597-66vd2mdu 932 21 . . . cord-014597-66vd2mdu 933 1 Furthermore furthermore RB cord-014597-66vd2mdu 933 2 , , , cord-014597-66vd2mdu 933 3 the the DT cord-014597-66vd2mdu 933 4 platform platform NN cord-014597-66vd2mdu 933 5 allows allow VBZ cord-014597-66vd2mdu 933 6 for for IN cord-014597-66vd2mdu 933 7 seamless seamless JJ cord-014597-66vd2mdu 933 8 integration integration NN cord-014597-66vd2mdu 933 9 with with IN cord-014597-66vd2mdu 933 10 laboratory laboratory NN cord-014597-66vd2mdu 933 11 instruments instrument NNS cord-014597-66vd2mdu 933 12 , , , cord-014597-66vd2mdu 933 13 statistical statistical JJ cord-014597-66vd2mdu 933 14 software software NN cord-014597-66vd2mdu 933 15 packages package NNS cord-014597-66vd2mdu 933 16 , , , cord-014597-66vd2mdu 933 17 and and CC cord-014597-66vd2mdu 933 18 custom custom NN cord-014597-66vd2mdu 933 19 solutions solution NNS cord-014597-66vd2mdu 933 20 . . . cord-014597-66vd2mdu 934 1 Here here RB cord-014597-66vd2mdu 934 2 , , , cord-014597-66vd2mdu 934 3 we -PRON- PRP cord-014597-66vd2mdu 934 4 present present VBP cord-014597-66vd2mdu 934 5 use use NN cord-014597-66vd2mdu 934 6 cases case NNS cord-014597-66vd2mdu 934 7 showing show VBG cord-014597-66vd2mdu 934 8 how how WRB cord-014597-66vd2mdu 934 9 to to TO cord-014597-66vd2mdu 934 10 identify identify VB cord-014597-66vd2mdu 934 11 and and CC cord-014597-66vd2mdu 934 12 annotate annotate VB cord-014597-66vd2mdu 934 13 liability liability NN cord-014597-66vd2mdu 934 14 sites site NNS cord-014597-66vd2mdu 934 15 prone prone JJ cord-014597-66vd2mdu 934 16 to to IN cord-014597-66vd2mdu 934 17 chemical chemical JJ cord-014597-66vd2mdu 934 18 modifications modification NNS cord-014597-66vd2mdu 934 19 ( ( -LRB- cord-014597-66vd2mdu 934 20 Fig Fig NNP cord-014597-66vd2mdu 934 21 . . . cord-014597-66vd2mdu 934 22 1a 1a CD cord-014597-66vd2mdu 934 23 ) ) -RRB- cord-014597-66vd2mdu 934 24 and and CC cord-014597-66vd2mdu 934 25 how how WRB cord-014597-66vd2mdu 934 26 to to TO cord-014597-66vd2mdu 934 27 monitor monitor VB cord-014597-66vd2mdu 934 28 CQAs cqa NNS cord-014597-66vd2mdu 934 29 of of IN cord-014597-66vd2mdu 934 30 molecules molecule NNS cord-014597-66vd2mdu 934 31 allowing allow VBG cord-014597-66vd2mdu 934 32 to to TO cord-014597-66vd2mdu 934 33 assess assess VB cord-014597-66vd2mdu 934 34 developability developability NN cord-014597-66vd2mdu 934 35 more more RBR cord-014597-66vd2mdu 934 36 efficiently efficiently RB cord-014597-66vd2mdu 934 37 . . . cord-014597-66vd2mdu 935 1 We -PRON- PRP cord-014597-66vd2mdu 935 2 show show VBP cord-014597-66vd2mdu 935 3 how how WRB cord-014597-66vd2mdu 935 4 the the DT cord-014597-66vd2mdu 935 5 analytical analytical JJ cord-014597-66vd2mdu 935 6 data datum NNS cord-014597-66vd2mdu 935 7 generated generate VBN cord-014597-66vd2mdu 935 8 in in IN cord-014597-66vd2mdu 935 9 the the DT cord-014597-66vd2mdu 935 10 course course NN cord-014597-66vd2mdu 935 11 of of IN cord-014597-66vd2mdu 935 12 a a DT cord-014597-66vd2mdu 935 13 developability developability NN cord-014597-66vd2mdu 935 14 assessment assessment NN cord-014597-66vd2mdu 935 15 are be VBP cord-014597-66vd2mdu 935 16 compiled compile VBN cord-014597-66vd2mdu 935 17 to to TO cord-014597-66vd2mdu 935 18 select select VB cord-014597-66vd2mdu 935 19 the the DT cord-014597-66vd2mdu 935 20 best good JJS cord-014597-66vd2mdu 935 21 drug drug NN cord-014597-66vd2mdu 935 22 candidate candidate NN cord-014597-66vd2mdu 935 23 ( ( -LRB- cord-014597-66vd2mdu 935 24 Fig Fig NNP cord-014597-66vd2mdu 935 25 . . . cord-014597-66vd2mdu 935 26 1b 1b CD cord-014597-66vd2mdu 935 27 ) ) -RRB- cord-014597-66vd2mdu 935 28 . . . cord-014597-66vd2mdu 936 1 Implemented implement VBN cord-014597-66vd2mdu 936 2 traffic traffic NN cord-014597-66vd2mdu 936 3 - - HYPH cord-014597-66vd2mdu 936 4 light light NN cord-014597-66vd2mdu 936 5 systems system NNS cord-014597-66vd2mdu 936 6 indicate indicate VBP cord-014597-66vd2mdu 936 7 where where WRB cord-014597-66vd2mdu 936 8 molecules molecule NNS cord-014597-66vd2mdu 936 9 harbor harbor VBP cord-014597-66vd2mdu 936 10 issues issue NNS cord-014597-66vd2mdu 936 11 such such JJ cord-014597-66vd2mdu 936 12 as as IN cord-014597-66vd2mdu 936 13 in in IN cord-014597-66vd2mdu 936 14 case case NN cord-014597-66vd2mdu 936 15 of of IN cord-014597-66vd2mdu 936 16 the the DT cord-014597-66vd2mdu 936 17 antibody antibody NN cord-014597-66vd2mdu 936 18 TPP-86 TPP-86 NNP cord-014597-66vd2mdu 936 19 , , , cord-014597-66vd2mdu 936 20 which which WDT cord-014597-66vd2mdu 936 21 is be VBZ cord-014597-66vd2mdu 936 22 compromised compromise VBN cord-014597-66vd2mdu 936 23 by by IN cord-014597-66vd2mdu 936 24 low low JJ cord-014597-66vd2mdu 936 25 temperature temperature NN cord-014597-66vd2mdu 936 26 and and CC cord-014597-66vd2mdu 936 27 repeated repeat VBD cord-014597-66vd2mdu 936 28 freeze freeze NN cord-014597-66vd2mdu 936 29 - - HYPH cord-014597-66vd2mdu 936 30 thaw thaw NN cord-014597-66vd2mdu 936 31 operations operation NNS cord-014597-66vd2mdu 936 32 . . . cord-014597-66vd2mdu 937 1 The the DT cord-014597-66vd2mdu 937 2 same same JJ cord-014597-66vd2mdu 937 3 assessment assessment NN cord-014597-66vd2mdu 937 4 views view NNS cord-014597-66vd2mdu 937 5 can can MD cord-014597-66vd2mdu 937 6 also also RB cord-014597-66vd2mdu 937 7 be be VB cord-014597-66vd2mdu 937 8 applied apply VBN cord-014597-66vd2mdu 937 9 on on IN cord-014597-66vd2mdu 937 10 batches batch NNS cord-014597-66vd2mdu 937 11 and and CC cord-014597-66vd2mdu 937 12 cell cell NN cord-014597-66vd2mdu 937 13 lines line NNS cord-014597-66vd2mdu 937 14 . . . cord-014597-66vd2mdu 938 1 The the DT cord-014597-66vd2mdu 938 2 underlying underlie VBG cord-014597-66vd2mdu 938 3 data datum NNS cord-014597-66vd2mdu 938 4 can can MD cord-014597-66vd2mdu 938 5 be be VB cord-014597-66vd2mdu 938 6 visualized visualize VBN cord-014597-66vd2mdu 938 7 graphically graphically RB cord-014597-66vd2mdu 938 8 . . . cord-014597-66vd2mdu 939 1 As as IN cord-014597-66vd2mdu 939 2 an an DT cord-014597-66vd2mdu 939 3 example example NN cord-014597-66vd2mdu 939 4 , , , cord-014597-66vd2mdu 939 5 we -PRON- PRP cord-014597-66vd2mdu 939 6 show show VBP cord-014597-66vd2mdu 939 7 glycan glycan NN cord-014597-66vd2mdu 939 8 types type NNS cord-014597-66vd2mdu 939 9 of of IN cord-014597-66vd2mdu 939 10 products product NNS cord-014597-66vd2mdu 939 11 obtained obtain VBN cord-014597-66vd2mdu 939 12 from from IN cord-014597-66vd2mdu 939 13 different different JJ cord-014597-66vd2mdu 939 14 cell cell NN cord-014597-66vd2mdu 939 15 line line NN cord-014597-66vd2mdu 939 16 clones clone NNS cord-014597-66vd2mdu 939 17 generated generate VBN cord-014597-66vd2mdu 939 18 in in IN cord-014597-66vd2mdu 939 19 a a DT cord-014597-66vd2mdu 939 20 cell cell NN cord-014597-66vd2mdu 939 21 line line NN cord-014597-66vd2mdu 939 22 development development NN cord-014597-66vd2mdu 939 23 campaign campaign NN cord-014597-66vd2mdu 939 24 for for IN cord-014597-66vd2mdu 939 25 the the DT cord-014597-66vd2mdu 939 26 molecule molecule NN cord-014597-66vd2mdu 939 27 TPP-86 TPP-86 NNP cord-014597-66vd2mdu 939 28 ( ( -LRB- cord-014597-66vd2mdu 939 29 Fig Fig NNP cord-014597-66vd2mdu 939 30 . . . cord-014597-66vd2mdu 939 31 1c 1c CD cord-014597-66vd2mdu 939 32 ) ) -RRB- cord-014597-66vd2mdu 939 33 . . . cord-014597-66vd2mdu 940 1 Even even RB cord-014597-66vd2mdu 940 2 though though IN cord-014597-66vd2mdu 940 3 the the DT cord-014597-66vd2mdu 940 4 selected select VBN cord-014597-66vd2mdu 940 5 clone clone NN cord-014597-66vd2mdu 940 6 CLI-35 CLI-35 NNP cord-014597-66vd2mdu 940 7 meets meet VBZ cord-014597-66vd2mdu 940 8 the the DT cord-014597-66vd2mdu 940 9 glycosylation glycosylation NN cord-014597-66vd2mdu 940 10 criteria criterion NNS cord-014597-66vd2mdu 940 11 ( ( -LRB- cord-014597-66vd2mdu 940 12 e. e. NNP cord-014597-66vd2mdu 940 13 g. g. NNP cord-014597-66vd2mdu 940 14 , , , cord-014597-66vd2mdu 940 15 < < NNP cord-014597-66vd2mdu 940 16 13 13 CD cord-014597-66vd2mdu 940 17 % % NN cord-014597-66vd2mdu 940 18 afucosylation afucosylation NN cord-014597-66vd2mdu 940 19 , , , cord-014597-66vd2mdu 940 20 < < XX cord-014597-66vd2mdu 940 21 40 40 CD cord-014597-66vd2mdu 940 22 % % NN cord-014597-66vd2mdu 940 23 galactosylation galactosylation NN cord-014597-66vd2mdu 940 24 , , , cord-014597-66vd2mdu 940 25 < < XX cord-014597-66vd2mdu 940 26 2 2 CD cord-014597-66vd2mdu 940 27 % % NN cord-014597-66vd2mdu 940 28 sialylation sialylation NN cord-014597-66vd2mdu 940 29 ) ) -RRB- cord-014597-66vd2mdu 940 30 , , , cord-014597-66vd2mdu 940 31 the the DT cord-014597-66vd2mdu 940 32 produced produce VBN cord-014597-66vd2mdu 940 33 Next Next NNP cord-014597-66vd2mdu 940 34 - - HYPH cord-014597-66vd2mdu 940 35 generation generation NN cord-014597-66vd2mdu 940 36 biologics biologic NNS cord-014597-66vd2mdu 940 37 molecules molecule NNS cord-014597-66vd2mdu 940 38 are be VBP cord-014597-66vd2mdu 940 39 composed compose VBN cord-014597-66vd2mdu 940 40 from from IN cord-014597-66vd2mdu 940 41 a a DT cord-014597-66vd2mdu 940 42 number number NN cord-014597-66vd2mdu 940 43 of of IN cord-014597-66vd2mdu 940 44 specific specific JJ cord-014597-66vd2mdu 940 45 subdomains subdomain NNS cord-014597-66vd2mdu 940 46 . . . cord-014597-66vd2mdu 941 1 Each each DT cord-014597-66vd2mdu 941 2 type type NN cord-014597-66vd2mdu 941 3 of of IN cord-014597-66vd2mdu 941 4 molecule molecule NN cord-014597-66vd2mdu 941 5 is be VBZ cord-014597-66vd2mdu 941 6 composed compose VBN cord-014597-66vd2mdu 941 7 of of IN cord-014597-66vd2mdu 941 8 a a DT cord-014597-66vd2mdu 941 9 specific specific JJ cord-014597-66vd2mdu 941 10 set set NN cord-014597-66vd2mdu 941 11 of of IN cord-014597-66vd2mdu 941 12 domains domain NNS cord-014597-66vd2mdu 941 13 , , , cord-014597-66vd2mdu 941 14 which which WDT cord-014597-66vd2mdu 941 15 must must MD cord-014597-66vd2mdu 941 16 be be VB cord-014597-66vd2mdu 941 17 mirrored mirror VBN cord-014597-66vd2mdu 941 18 in in IN cord-014597-66vd2mdu 941 19 the the DT cord-014597-66vd2mdu 941 20 registration registration NN cord-014597-66vd2mdu 941 21 and and CC cord-014597-66vd2mdu 941 22 further further JJ cord-014597-66vd2mdu 941 23 research research NN cord-014597-66vd2mdu 941 24 and and CC cord-014597-66vd2mdu 941 25 development development NN cord-014597-66vd2mdu 941 26 workflow workflow NN cord-014597-66vd2mdu 941 27 . . . cord-014597-66vd2mdu 942 1 Molecule molecule NN cord-014597-66vd2mdu 942 2 registration registration NN cord-014597-66vd2mdu 942 3 and and CC cord-014597-66vd2mdu 942 4 hit hit NN cord-014597-66vd2mdu 942 5 - - HYPH cord-014597-66vd2mdu 942 6 selection selection NN cord-014597-66vd2mdu 943 1 using use VBG cord-014597-66vd2mdu 943 2 data datum NNS cord-014597-66vd2mdu 943 3 from from IN cord-014597-66vd2mdu 943 4 a a DT cord-014597-66vd2mdu 943 5 number number NN cord-014597-66vd2mdu 943 6 of of IN cord-014597-66vd2mdu 943 7 assays assay NNS cord-014597-66vd2mdu 943 8 is be VBZ cord-014597-66vd2mdu 943 9 shown show VBN cord-014597-66vd2mdu 943 10 here here RB cord-014597-66vd2mdu 943 11 using use VBG cord-014597-66vd2mdu 943 12 the the DT cord-014597-66vd2mdu 943 13 example example NN cord-014597-66vd2mdu 943 14 of of IN cord-014597-66vd2mdu 943 15 CAR car NN cord-014597-66vd2mdu 943 16 - - HYPH cord-014597-66vd2mdu 943 17 T t NN cord-014597-66vd2mdu 943 18 cells cell NNS cord-014597-66vd2mdu 943 19 . . . cord-014597-66vd2mdu 944 1 The the DT cord-014597-66vd2mdu 944 2 image image NN cord-014597-66vd2mdu 944 3 is be VBZ cord-014597-66vd2mdu 944 4 a a DT cord-014597-66vd2mdu 944 5 screenshot screenshot NN cord-014597-66vd2mdu 944 6 from from IN cord-014597-66vd2mdu 944 7 the the DT cord-014597-66vd2mdu 944 8 Genedata Genedata NNP cord-014597-66vd2mdu 944 9 Biologics Biologics NNP cord-014597-66vd2mdu 944 10 ™ ™ NN cord-014597-66vd2mdu 944 11 software software NN cord-014597-66vd2mdu 944 12 molecule molecule NN cord-014597-66vd2mdu 944 13 harbors harbor VBZ cord-014597-66vd2mdu 944 14 some some DT cord-014597-66vd2mdu 944 15 stability stability NN cord-014597-66vd2mdu 944 16 issues issue NNS cord-014597-66vd2mdu 944 17 as as IN cord-014597-66vd2mdu 944 18 mentioned mention VBN cord-014597-66vd2mdu 944 19 above above RB cord-014597-66vd2mdu 944 20 . . . cord-014597-66vd2mdu 945 1 Therefore therefore RB cord-014597-66vd2mdu 945 2 , , , cord-014597-66vd2mdu 945 3 more more JJR cord-014597-66vd2mdu 945 4 attempts attempt NNS cord-014597-66vd2mdu 945 5 would would MD cord-014597-66vd2mdu 945 6 be be VB cord-014597-66vd2mdu 945 7 needed need VBN cord-014597-66vd2mdu 945 8 either either CC cord-014597-66vd2mdu 945 9 in in IN cord-014597-66vd2mdu 945 10 formulation formulation NN cord-014597-66vd2mdu 945 11 or or CC cord-014597-66vd2mdu 945 12 in in IN cord-014597-66vd2mdu 945 13 reengineering reengineering NN cord-014597-66vd2mdu 945 14 of of IN cord-014597-66vd2mdu 945 15 the the DT cord-014597-66vd2mdu 945 16 complimentarity complimentarity NN cord-014597-66vd2mdu 945 17 determining determine VBG cord-014597-66vd2mdu 945 18 regions region NNS cord-014597-66vd2mdu 945 19 ( ( -LRB- cord-014597-66vd2mdu 945 20 CDRs cdr NNS cord-014597-66vd2mdu 945 21 ) ) -RRB- cord-014597-66vd2mdu 945 22 in in IN cord-014597-66vd2mdu 945 23 order order NN cord-014597-66vd2mdu 945 24 to to TO cord-014597-66vd2mdu 945 25 provide provide VB cord-014597-66vd2mdu 945 26 a a DT cord-014597-66vd2mdu 945 27 developable developable JJ cord-014597-66vd2mdu 945 28 TTP-86-like TTP-86-like VBN cord-014597-66vd2mdu 945 29 drug drug NN cord-014597-66vd2mdu 945 30 candidate candidate NN cord-014597-66vd2mdu 945 31 . . . cord-014597-66vd2mdu 946 1 Background Background NNP cord-014597-66vd2mdu 946 2 Environmental environmental JJ cord-014597-66vd2mdu 946 3 process process NN cord-014597-66vd2mdu 946 4 variables variable NNS cord-014597-66vd2mdu 946 5 are be VBP cord-014597-66vd2mdu 946 6 often often RB cord-014597-66vd2mdu 946 7 used use VBN cord-014597-66vd2mdu 946 8 as as IN cord-014597-66vd2mdu 946 9 tools tool NNS cord-014597-66vd2mdu 946 10 to to TO cord-014597-66vd2mdu 946 11 optimize optimize VB cord-014597-66vd2mdu 946 12 the the DT cord-014597-66vd2mdu 946 13 performance performance NN cord-014597-66vd2mdu 946 14 of of IN cord-014597-66vd2mdu 946 15 mammalian mammalian JJ cord-014597-66vd2mdu 946 16 cell cell NN cord-014597-66vd2mdu 946 17 cultures culture NNS cord-014597-66vd2mdu 946 18 to to TO cord-014597-66vd2mdu 946 19 achieve achieve VB cord-014597-66vd2mdu 946 20 higher high JJR cord-014597-66vd2mdu 946 21 cell cell NN cord-014597-66vd2mdu 946 22 densities density NNS cord-014597-66vd2mdu 946 23 and and CC cord-014597-66vd2mdu 946 24 high high JJ cord-014597-66vd2mdu 946 25 productivities productivity NNS cord-014597-66vd2mdu 946 26 of of IN cord-014597-66vd2mdu 946 27 r r NN cord-014597-66vd2mdu 946 28 - - HYPH cord-014597-66vd2mdu 946 29 proteins protein NNS cord-014597-66vd2mdu 946 30 ( ( -LRB- cord-014597-66vd2mdu 946 31 q q NNP cord-014597-66vd2mdu 946 32 P P NNP cord-014597-66vd2mdu 946 33 ) ) -RRB- cord-014597-66vd2mdu 946 34 . . . cord-014597-66vd2mdu 947 1 The the DT cord-014597-66vd2mdu 947 2 manipulation manipulation NN cord-014597-66vd2mdu 947 3 of of IN cord-014597-66vd2mdu 947 4 culture culture NN cord-014597-66vd2mdu 947 5 temperature temperature NN cord-014597-66vd2mdu 947 6 in in IN cord-014597-66vd2mdu 947 7 the the DT cord-014597-66vd2mdu 947 8 range range NN cord-014597-66vd2mdu 947 9 of of IN cord-014597-66vd2mdu 947 10 mild mild JJ cord-014597-66vd2mdu 947 11 hypothermia hypothermia NN cord-014597-66vd2mdu 947 12 ( ( -LRB- cord-014597-66vd2mdu 947 13 MH MH NNP cord-014597-66vd2mdu 947 14 ) ) -RRB- cord-014597-66vd2mdu 947 15 ( ( -LRB- cord-014597-66vd2mdu 947 16 35 35 CD cord-014597-66vd2mdu 947 17 - - SYM cord-014597-66vd2mdu 947 18 30 30 CD cord-014597-66vd2mdu 947 19 ° ° NN cord-014597-66vd2mdu 947 20 C c NN cord-014597-66vd2mdu 947 21 ) ) -RRB- cord-014597-66vd2mdu 947 22 [ [ -LRB- cord-014597-66vd2mdu 947 23 1 1 CD cord-014597-66vd2mdu 947 24 , , , cord-014597-66vd2mdu 947 25 2 2 CD cord-014597-66vd2mdu 947 26 ] ] -RRB- cord-014597-66vd2mdu 947 27 , , , cord-014597-66vd2mdu 947 28 as as RB cord-014597-66vd2mdu 947 29 well well RB cord-014597-66vd2mdu 947 30 as as IN cord-014597-66vd2mdu 947 31 different different JJ cord-014597-66vd2mdu 947 32 glucose glucose NN cord-014597-66vd2mdu 947 33 availability availability NN cord-014597-66vd2mdu 947 34 scenarios scenario NNS cord-014597-66vd2mdu 947 35 [ [ -LRB- cord-014597-66vd2mdu 947 36 3 3 CD cord-014597-66vd2mdu 947 37 , , , cord-014597-66vd2mdu 947 38 4 4 CD cord-014597-66vd2mdu 947 39 ] ] -RRB- cord-014597-66vd2mdu 947 40 , , , cord-014597-66vd2mdu 947 41 has have VBZ cord-014597-66vd2mdu 947 42 been be VBN cord-014597-66vd2mdu 947 43 shown show VBN cord-014597-66vd2mdu 947 44 to to TO cord-014597-66vd2mdu 947 45 improve improve VB cord-014597-66vd2mdu 947 46 productivity productivity NN cord-014597-66vd2mdu 947 47 in in IN cord-014597-66vd2mdu 947 48 different different JJ cord-014597-66vd2mdu 947 49 cell cell NN cord-014597-66vd2mdu 947 50 lines line NNS cord-014597-66vd2mdu 947 51 . . . cord-014597-66vd2mdu 948 1 However however RB cord-014597-66vd2mdu 948 2 , , , cord-014597-66vd2mdu 948 3 the the DT cord-014597-66vd2mdu 948 4 manipulation manipulation NN cord-014597-66vd2mdu 948 5 of of IN cord-014597-66vd2mdu 948 6 these these DT cord-014597-66vd2mdu 948 7 variables variable NNS cord-014597-66vd2mdu 948 8 individually individually RB cord-014597-66vd2mdu 948 9 or or CC cord-014597-66vd2mdu 948 10 together together RB cord-014597-66vd2mdu 948 11 has have VBZ cord-014597-66vd2mdu 948 12 a a DT cord-014597-66vd2mdu 948 13 concomitant concomitant JJ cord-014597-66vd2mdu 948 14 effect effect NN cord-014597-66vd2mdu 948 15 on on IN cord-014597-66vd2mdu 948 16 the the DT cord-014597-66vd2mdu 948 17 rate rate NN cord-014597-66vd2mdu 948 18 at at IN cord-014597-66vd2mdu 948 19 which which WDT cord-014597-66vd2mdu 948 20 cells cell NNS cord-014597-66vd2mdu 948 21 grow grow VBP cord-014597-66vd2mdu 948 22 , , , cord-014597-66vd2mdu 948 23 masking mask VBG cord-014597-66vd2mdu 948 24 the the DT cord-014597-66vd2mdu 948 25 net net JJ cord-014597-66vd2mdu 948 26 response response NN cord-014597-66vd2mdu 948 27 exhibited exhibit VBN cord-014597-66vd2mdu 948 28 by by IN cord-014597-66vd2mdu 948 29 the the DT cord-014597-66vd2mdu 948 30 cells cell NNS cord-014597-66vd2mdu 948 31 . . . cord-014597-66vd2mdu 949 1 In in IN cord-014597-66vd2mdu 949 2 order order NN cord-014597-66vd2mdu 949 3 to to TO cord-014597-66vd2mdu 949 4 identify identify VB cord-014597-66vd2mdu 949 5 the the DT cord-014597-66vd2mdu 949 6 effects effect NNS cord-014597-66vd2mdu 949 7 of of IN cord-014597-66vd2mdu 949 8 these these DT cord-014597-66vd2mdu 949 9 variables variable NNS cord-014597-66vd2mdu 949 10 , , , cord-014597-66vd2mdu 949 11 we -PRON- PRP cord-014597-66vd2mdu 949 12 have have VBP cord-014597-66vd2mdu 949 13 taken take VBN cord-014597-66vd2mdu 949 14 advantage advantage NN cord-014597-66vd2mdu 949 15 of of IN cord-014597-66vd2mdu 949 16 the the DT cord-014597-66vd2mdu 949 17 use use NN cord-014597-66vd2mdu 949 18 of of IN cord-014597-66vd2mdu 949 19 the the DT cord-014597-66vd2mdu 949 20 chemostat chemostat NNP cord-014597-66vd2mdu 949 21 culture culture NN cord-014597-66vd2mdu 949 22 . . . cord-014597-66vd2mdu 950 1 Chemostat Chemostat NNP cord-014597-66vd2mdu 950 2 cultures culture NNS cord-014597-66vd2mdu 950 3 were be VBD cord-014597-66vd2mdu 950 4 performed perform VBN cord-014597-66vd2mdu 950 5 at at IN cord-014597-66vd2mdu 950 6 two two CD cord-014597-66vd2mdu 950 7 dilution dilution NN cord-014597-66vd2mdu 950 8 rate rate NN cord-014597-66vd2mdu 950 9 ( ( -LRB- cord-014597-66vd2mdu 950 10 D)(0.010 D)(0.010 NNP cord-014597-66vd2mdu 950 11 or or CC cord-014597-66vd2mdu 950 12 0.018(h-1 0.018(h-1 NN cord-014597-66vd2mdu 950 13 ) ) -RRB- cord-014597-66vd2mdu 950 14 ) ) -RRB- cord-014597-66vd2mdu 950 15 , , , cord-014597-66vd2mdu 950 16 two two CD cord-014597-66vd2mdu 950 17 temperatures temperature NNS cord-014597-66vd2mdu 950 18 ( ( -LRB- cord-014597-66vd2mdu 950 19 33 33 CD cord-014597-66vd2mdu 950 20 or or CC cord-014597-66vd2mdu 950 21 37 37 CD cord-014597-66vd2mdu 950 22 ° ° NN cord-014597-66vd2mdu 950 23 C c NN cord-014597-66vd2mdu 950 24 ) ) -RRB- cord-014597-66vd2mdu 950 25 and and CC cord-014597-66vd2mdu 950 26 three three CD cord-014597-66vd2mdu 950 27 feed feed NN cord-014597-66vd2mdu 950 28 glucose glucose NN cord-014597-66vd2mdu 950 29 concentrations concentration NNS cord-014597-66vd2mdu 950 30 ( ( -LRB- cord-014597-66vd2mdu 950 31 20 20 CD cord-014597-66vd2mdu 950 32 , , , cord-014597-66vd2mdu 950 33 30 30 CD cord-014597-66vd2mdu 950 34 or or CC cord-014597-66vd2mdu 950 35 40 40 CD cord-014597-66vd2mdu 950 36 mM mm CD cord-014597-66vd2mdu 950 37 ) ) -RRB- cord-014597-66vd2mdu 950 38 . . . cord-014597-66vd2mdu 951 1 The the DT cord-014597-66vd2mdu 951 2 response response NN cord-014597-66vd2mdu 951 3 was be VBD cord-014597-66vd2mdu 951 4 analysed analyse VBN cord-014597-66vd2mdu 951 5 considering consider VBG cord-014597-66vd2mdu 951 6 r r NN cord-014597-66vd2mdu 951 7 - - HYPH cord-014597-66vd2mdu 951 8 protein protein NN cord-014597-66vd2mdu 951 9 production production NN cord-014597-66vd2mdu 951 10 , , , cord-014597-66vd2mdu 951 11 cell cell NN cord-014597-66vd2mdu 951 12 growth growth NN cord-014597-66vd2mdu 951 13 and and CC cord-014597-66vd2mdu 951 14 key key JJ cord-014597-66vd2mdu 951 15 metabolites metabolite NNS cord-014597-66vd2mdu 951 16 . . . cord-014597-66vd2mdu 952 1 r r LS cord-014597-66vd2mdu 952 2 - - : cord-014597-66vd2mdu 952 3 tPA tpa NN cord-014597-66vd2mdu 952 4 protein protein NN cord-014597-66vd2mdu 952 5 concentration concentration NN cord-014597-66vd2mdu 952 6 was be VBD cord-014597-66vd2mdu 952 7 determined determine VBN cord-014597-66vd2mdu 952 8 by by IN cord-014597-66vd2mdu 952 9 immunoassay immunoassay JJ cord-014597-66vd2mdu 952 10 ( ( -LRB- cord-014597-66vd2mdu 952 11 TriniLIZE TriniLIZE NNP cord-014597-66vd2mdu 952 12 tPA tPA NNP cord-014597-66vd2mdu 952 13 KIT kit NN cord-014597-66vd2mdu 952 14 ) ) -RRB- cord-014597-66vd2mdu 952 15 ; ; : cord-014597-66vd2mdu 952 16 cells cell NNS cord-014597-66vd2mdu 952 17 were be VBD cord-014597-66vd2mdu 952 18 counted count VBN cord-014597-66vd2mdu 952 19 using use VBG cord-014597-66vd2mdu 952 20 a a DT cord-014597-66vd2mdu 952 21 hemocytometer hemocytometer NN cord-014597-66vd2mdu 952 22 and and CC cord-014597-66vd2mdu 952 23 cell cell NN cord-014597-66vd2mdu 952 24 viability viability NN cord-014597-66vd2mdu 952 25 was be VBD cord-014597-66vd2mdu 952 26 determined determine VBN cord-014597-66vd2mdu 952 27 by by IN cord-014597-66vd2mdu 952 28 the the DT cord-014597-66vd2mdu 952 29 method method NN cord-014597-66vd2mdu 952 30 of of IN cord-014597-66vd2mdu 952 31 exclusion exclusion NN cord-014597-66vd2mdu 952 32 using use VBG cord-014597-66vd2mdu 952 33 trypan trypan NNP cord-014597-66vd2mdu 952 34 blue blue NNP cord-014597-66vd2mdu 952 35 ( ( -LRB- cord-014597-66vd2mdu 952 36 T8154 T8154 NNP cord-014597-66vd2mdu 952 37 , , , cord-014597-66vd2mdu 952 38 Sigma Sigma NNP cord-014597-66vd2mdu 952 39 , , , cord-014597-66vd2mdu 952 40 USA USA NNP cord-014597-66vd2mdu 952 41 ) ) -RRB- cord-014597-66vd2mdu 952 42 ; ; : cord-014597-66vd2mdu 952 43 glucose glucose NN cord-014597-66vd2mdu 952 44 , , , cord-014597-66vd2mdu 952 45 lactate lactate NN cord-014597-66vd2mdu 952 46 and and CC cord-014597-66vd2mdu 952 47 glutamate glutamate NN cord-014597-66vd2mdu 952 48 were be VBD cord-014597-66vd2mdu 952 49 determined determine VBN cord-014597-66vd2mdu 952 50 by by IN cord-014597-66vd2mdu 952 51 enzymatic enzymatic JJ cord-014597-66vd2mdu 952 52 assay assay NN cord-014597-66vd2mdu 952 53 using use VBG cord-014597-66vd2mdu 952 54 a a DT cord-014597-66vd2mdu 952 55 biochemical biochemical JJ cord-014597-66vd2mdu 952 56 analyser analyser NN cord-014597-66vd2mdu 952 57 YSI YSI NNP cord-014597-66vd2mdu 952 58 ( ( -LRB- cord-014597-66vd2mdu 952 59 Yellow Yellow NNP cord-014597-66vd2mdu 952 60 Spring Spring NNP cord-014597-66vd2mdu 952 61 Instruments Instruments NNP cord-014597-66vd2mdu 952 62 ) ) -RRB- cord-014597-66vd2mdu 952 63 . . . cord-014597-66vd2mdu 953 1 Statistical statistical JJ cord-014597-66vd2mdu 953 2 analysis analysis NN cord-014597-66vd2mdu 953 3 of of IN cord-014597-66vd2mdu 953 4 the the DT cord-014597-66vd2mdu 953 5 results result NNS cord-014597-66vd2mdu 953 6 was be VBD cord-014597-66vd2mdu 953 7 performed perform VBN cord-014597-66vd2mdu 953 8 by by IN cord-014597-66vd2mdu 953 9 ANOVA ANOVA NNP cord-014597-66vd2mdu 953 10 ( ( -LRB- cord-014597-66vd2mdu 953 11 Design Design NNP cord-014597-66vd2mdu 953 12 - - HYPH cord-014597-66vd2mdu 953 13 Expert Expert NNP cord-014597-66vd2mdu 953 14 7 7 CD cord-014597-66vd2mdu 953 15 for for IN cord-014597-66vd2mdu 953 16 Windows Windows NNP cord-014597-66vd2mdu 953 17 ) ) -RRB- cord-014597-66vd2mdu 953 18 . . . cord-014597-66vd2mdu 954 1 A a DT cord-014597-66vd2mdu 954 2 decrease decrease NN cord-014597-66vd2mdu 954 3 in in IN cord-014597-66vd2mdu 954 4 cell cell NN cord-014597-66vd2mdu 954 5 density density NN cord-014597-66vd2mdu 954 6 was be VBD cord-014597-66vd2mdu 954 7 observed observe VBN cord-014597-66vd2mdu 954 8 in in IN cord-014597-66vd2mdu 954 9 response response NN cord-014597-66vd2mdu 954 10 to to IN cord-014597-66vd2mdu 954 11 an an DT cord-014597-66vd2mdu 954 12 increase increase NN cord-014597-66vd2mdu 954 13 of of IN cord-014597-66vd2mdu 954 14 glucose glucose NN cord-014597-66vd2mdu 954 15 feeding feeding NN cord-014597-66vd2mdu 954 16 concentration concentration NN cord-014597-66vd2mdu 954 17 , , , cord-014597-66vd2mdu 954 18 regardless regardless RB cord-014597-66vd2mdu 954 19 of of IN cord-014597-66vd2mdu 954 20 temperature temperature NN cord-014597-66vd2mdu 954 21 or or CC cord-014597-66vd2mdu 954 22 specific specific JJ cord-014597-66vd2mdu 954 23 growth growth NN cord-014597-66vd2mdu 954 24 rate rate NN cord-014597-66vd2mdu 954 25 ( ( -LRB- cord-014597-66vd2mdu 954 26 in in IN cord-014597-66vd2mdu 954 27 this this DT cord-014597-66vd2mdu 954 28 case case NN cord-014597-66vd2mdu 954 29 μ μ NN cord-014597-66vd2mdu 954 30 = = SYM cord-014597-66vd2mdu 954 31 D D NNP cord-014597-66vd2mdu 954 32 ) ) -RRB- cord-014597-66vd2mdu 954 33 evaluated evaluate VBN cord-014597-66vd2mdu 954 34 . . . cord-014597-66vd2mdu 955 1 The the DT cord-014597-66vd2mdu 955 2 maximum maximum JJ cord-014597-66vd2mdu 955 3 cell cell NN cord-014597-66vd2mdu 955 4 densities density NNS cord-014597-66vd2mdu 955 5 were be VBD cord-014597-66vd2mdu 955 6 reached reach VBN cord-014597-66vd2mdu 955 7 at at IN cord-014597-66vd2mdu 955 8 20mM 20mm CD cord-014597-66vd2mdu 955 9 , , , cord-014597-66vd2mdu 955 10 achieving achieve VBG cord-014597-66vd2mdu 955 11 1.65 1.65 CD cord-014597-66vd2mdu 955 12 and and CC cord-014597-66vd2mdu 955 13 1.50 1.50 CD cord-014597-66vd2mdu 955 14 x10 x10 CD cord-014597-66vd2mdu 955 15 6 6 CD cord-014597-66vd2mdu 955 16 cells cell NNS cord-014597-66vd2mdu 956 1 /ml /ml NFP cord-014597-66vd2mdu 956 2 at at IN cord-014597-66vd2mdu 956 3 37/33 37/33 CD cord-014597-66vd2mdu 956 4 ° ° NN cord-014597-66vd2mdu 956 5 C c NN cord-014597-66vd2mdu 956 6 and and CC cord-014597-66vd2mdu 956 7 0.018(h 0.018(h CD cord-014597-66vd2mdu 956 8 -1 -1 NN cord-014597-66vd2mdu 956 9 ) ) -RRB- cord-014597-66vd2mdu 956 10 ; ; : cord-014597-66vd2mdu 956 11 and and CC cord-014597-66vd2mdu 956 12 1.10 1.10 CD cord-014597-66vd2mdu 956 13 and and CC cord-014597-66vd2mdu 956 14 1.33 1.33 CD cord-014597-66vd2mdu 956 15 x x SYM cord-014597-66vd2mdu 956 16 10 10 CD cord-014597-66vd2mdu 956 17 6 6 CD cord-014597-66vd2mdu 956 18 cells cell NNS cord-014597-66vd2mdu 956 19 / / SYM cord-014597-66vd2mdu 956 20 ml ml NN cord-014597-66vd2mdu 956 21 at at IN cord-014597-66vd2mdu 956 22 37/33 37/33 CD cord-014597-66vd2mdu 956 23 ° ° NN cord-014597-66vd2mdu 956 24 C c NN cord-014597-66vd2mdu 956 25 and and CC cord-014597-66vd2mdu 956 26 0.010(h 0.010(h CD cord-014597-66vd2mdu 956 27 -1 -1 NN cord-014597-66vd2mdu 956 28 ) ) -RRB- cord-014597-66vd2mdu 957 1 respectively respectively RB cord-014597-66vd2mdu 957 2 ( ( -LRB- cord-014597-66vd2mdu 957 3 Fig Fig NNP cord-014597-66vd2mdu 957 4 . . . cord-014597-66vd2mdu 957 5 1a 1a CD cord-014597-66vd2mdu 957 6 ) ) -RRB- cord-014597-66vd2mdu 957 7 . . . cord-014597-66vd2mdu 958 1 The the DT cord-014597-66vd2mdu 958 2 increase increase NN cord-014597-66vd2mdu 958 3 in in IN cord-014597-66vd2mdu 958 4 glucose glucose NN cord-014597-66vd2mdu 958 5 concentration concentration NN cord-014597-66vd2mdu 958 6 from from IN cord-014597-66vd2mdu 958 7 20 20 CD cord-014597-66vd2mdu 958 8 to to TO cord-014597-66vd2mdu 958 9 40mM 40mm CD cord-014597-66vd2mdu 958 10 resulted result VBD cord-014597-66vd2mdu 958 11 in in IN cord-014597-66vd2mdu 958 12 an an DT cord-014597-66vd2mdu 958 13 q q NN cord-014597-66vd2mdu 958 14 P p NN cord-014597-66vd2mdu 958 15 increase increase NN cord-014597-66vd2mdu 958 16 of of IN cord-014597-66vd2mdu 958 17 3 3 CD cord-014597-66vd2mdu 958 18 and and CC cord-014597-66vd2mdu 958 19 3.3 3.3 CD cord-014597-66vd2mdu 958 20 fold fold VB cord-014597-66vd2mdu 958 21 at at IN cord-014597-66vd2mdu 958 22 33 33 CD cord-014597-66vd2mdu 958 23 ° ° NN cord-014597-66vd2mdu 958 24 C/0.018(h C/0.018(h NNP cord-014597-66vd2mdu 958 25 -1 -1 NN cord-014597-66vd2mdu 958 26 ) ) -RRB- cord-014597-66vd2mdu 958 27 and and CC cord-014597-66vd2mdu 958 28 37 37 CD cord-014597-66vd2mdu 958 29 ° ° NN cord-014597-66vd2mdu 958 30 C/0.018(h C/0.018(h NNP cord-014597-66vd2mdu 958 31 -1 -1 NN cord-014597-66vd2mdu 958 32 ) ) -RRB- cord-014597-66vd2mdu 958 33 respectively respectively RB cord-014597-66vd2mdu 958 34 . . . cord-014597-66vd2mdu 959 1 A a DT cord-014597-66vd2mdu 959 2 lower low JJR cord-014597-66vd2mdu 959 3 increase increase NN cord-014597-66vd2mdu 959 4 of of IN cord-014597-66vd2mdu 959 5 2.4 2.4 CD cord-014597-66vd2mdu 959 6 and and CC cord-014597-66vd2mdu 959 7 1.8 1.8 CD cord-014597-66vd2mdu 959 8 fold fold NN cord-014597-66vd2mdu 959 9 was be VBD cord-014597-66vd2mdu 959 10 reached reach VBN cord-014597-66vd2mdu 959 11 at at IN cord-014597-66vd2mdu 959 12 33 33 CD cord-014597-66vd2mdu 959 13 ° ° NN cord-014597-66vd2mdu 959 14 C/0.010(h C/0.010(h NNP cord-014597-66vd2mdu 959 15 -1 -1 NNP cord-014597-66vd2mdu 959 16 ) ) -RRB- cord-014597-66vd2mdu 959 17 and and CC cord-014597-66vd2mdu 959 18 37 37 CD cord-014597-66vd2mdu 959 19 ° ° NN cord-014597-66vd2mdu 959 20 C/0.010(h C/0.010(h NNP cord-014597-66vd2mdu 959 21 -1 -1 NN cord-014597-66vd2mdu 959 22 ) ) -RRB- cord-014597-66vd2mdu 959 23 respectively respectively RB cord-014597-66vd2mdu 960 1 ( ( -LRB- cord-014597-66vd2mdu 960 2 Fig Fig NNP cord-014597-66vd2mdu 960 3 . . . cord-014597-66vd2mdu 960 4 1b 1b CD cord-014597-66vd2mdu 960 5 ) ) -RRB- cord-014597-66vd2mdu 960 6 . . . cord-014597-66vd2mdu 961 1 The the DT cord-014597-66vd2mdu 961 2 highest high JJS cord-014597-66vd2mdu 961 3 q q NN cord-014597-66vd2mdu 961 4 P P NNP cord-014597-66vd2mdu 961 5 s s NNS cord-014597-66vd2mdu 961 6 were be VBD cord-014597-66vd2mdu 961 7 reached reach VBN cord-014597-66vd2mdu 961 8 at at IN cord-014597-66vd2mdu 961 9 37 37 CD cord-014597-66vd2mdu 961 10 ° ° NN cord-014597-66vd2mdu 961 11 C c NN cord-014597-66vd2mdu 961 12 and and CC cord-014597-66vd2mdu 961 13 0.010(h 0.010(h CD cord-014597-66vd2mdu 961 14 -1 -1 NN cord-014597-66vd2mdu 961 15 ) ) -RRB- cord-014597-66vd2mdu 961 16 . . . cord-014597-66vd2mdu 962 1 However however RB cord-014597-66vd2mdu 962 2 , , , cord-014597-66vd2mdu 962 3 a a DT cord-014597-66vd2mdu 962 4 positive positive JJ cord-014597-66vd2mdu 962 5 effect effect NN cord-014597-66vd2mdu 962 6 of of IN cord-014597-66vd2mdu 962 7 MH MH NNP cord-014597-66vd2mdu 962 8 was be VBD cord-014597-66vd2mdu 962 9 not not RB cord-014597-66vd2mdu 962 10 observed observe VBN cord-014597-66vd2mdu 962 11 , , , cord-014597-66vd2mdu 962 12 in in IN cord-014597-66vd2mdu 962 13 contrast contrast NN cord-014597-66vd2mdu 962 14 to to IN cord-014597-66vd2mdu 962 15 that that DT cord-014597-66vd2mdu 962 16 observed observe VBN cord-014597-66vd2mdu 962 17 in in IN cord-014597-66vd2mdu 962 18 batch batch NN cord-014597-66vd2mdu 962 19 culture culture NN cord-014597-66vd2mdu 962 20 [ [ -LRB- cord-014597-66vd2mdu 962 21 1 1 CD cord-014597-66vd2mdu 962 22 , , , cord-014597-66vd2mdu 962 23 2 2 CD cord-014597-66vd2mdu 962 24 , , , cord-014597-66vd2mdu 962 25 3 3 CD cord-014597-66vd2mdu 962 26 ] ] -RRB- cord-014597-66vd2mdu 962 27 . . . cord-014597-66vd2mdu 963 1 This this DT cord-014597-66vd2mdu 963 2 behaviour behaviour NN cord-014597-66vd2mdu 963 3 suggests suggest VBZ cord-014597-66vd2mdu 963 4 that that IN cord-014597-66vd2mdu 963 5 low low JJ cord-014597-66vd2mdu 963 6 μ μ NN cord-014597-66vd2mdu 963 7 is be VBZ cord-014597-66vd2mdu 963 8 a a DT cord-014597-66vd2mdu 963 9 main main JJ cord-014597-66vd2mdu 963 10 factor factor NN cord-014597-66vd2mdu 963 11 on on IN cord-014597-66vd2mdu 963 12 increased increase VBN cord-014597-66vd2mdu 963 13 r r NN cord-014597-66vd2mdu 963 14 - - HYPH cord-014597-66vd2mdu 963 15 protein protein NN cord-014597-66vd2mdu 963 16 production production NN cord-014597-66vd2mdu 963 17 in in IN cord-014597-66vd2mdu 963 18 batch batch NN cord-014597-66vd2mdu 963 19 cultures culture NNS cord-014597-66vd2mdu 963 20 exposed expose VBN cord-014597-66vd2mdu 963 21 at at IN cord-014597-66vd2mdu 963 22 MH MH NNP cord-014597-66vd2mdu 963 23 condition condition NN cord-014597-66vd2mdu 963 24 . . . cord-014597-66vd2mdu 964 1 The the DT cord-014597-66vd2mdu 964 2 specific specific JJ cord-014597-66vd2mdu 964 3 consumption consumption NN cord-014597-66vd2mdu 964 4 rate rate NN cord-014597-66vd2mdu 964 5 of of IN cord-014597-66vd2mdu 964 6 glucose glucose NN cord-014597-66vd2mdu 964 7 was be VBD cord-014597-66vd2mdu 964 8 significantly significantly RB cord-014597-66vd2mdu 964 9 increased increase VBN cord-014597-66vd2mdu 964 10 by by IN cord-014597-66vd2mdu 964 11 the the DT cord-014597-66vd2mdu 964 12 glucose glucose NN cord-014597-66vd2mdu 964 13 increase increase NN cord-014597-66vd2mdu 964 14 from from IN cord-014597-66vd2mdu 964 15 20 20 CD cord-014597-66vd2mdu 964 16 to to TO cord-014597-66vd2mdu 964 17 40mM 40mm CD cord-014597-66vd2mdu 964 18 and and CC cord-014597-66vd2mdu 964 19 reduced reduce VBN cord-014597-66vd2mdu 964 20 by by IN cord-014597-66vd2mdu 964 21 MH MH NNP cord-014597-66vd2mdu 964 22 ( ( -LRB- cord-014597-66vd2mdu 964 23 Fig Fig NNP cord-014597-66vd2mdu 964 24 . . . cord-014597-66vd2mdu 964 25 _SP cord-014597-66vd2mdu 964 26 1c 1c CD cord-014597-66vd2mdu 964 27 ) ) -RRB- cord-014597-66vd2mdu 964 28 . . . cord-014597-66vd2mdu 965 1 At at IN cord-014597-66vd2mdu 965 2 0.010 0.010 CD cord-014597-66vd2mdu 965 3 ( ( -LRB- cord-014597-66vd2mdu 965 4 h h NN cord-014597-66vd2mdu 965 5 -1 -1 JJ cord-014597-66vd2mdu 965 6 ) ) -RRB- cord-014597-66vd2mdu 965 7 the the DT cord-014597-66vd2mdu 965 8 specific specific JJ cord-014597-66vd2mdu 965 9 production production NN cord-014597-66vd2mdu 965 10 rate rate NN cord-014597-66vd2mdu 965 11 of of IN cord-014597-66vd2mdu 965 12 lactate lactate NN cord-014597-66vd2mdu 965 13 ( ( -LRB- cord-014597-66vd2mdu 965 14 q q NNP cord-014597-66vd2mdu 965 15 Lac Lac NNP cord-014597-66vd2mdu 965 16 ) ) -RRB- cord-014597-66vd2mdu 965 17 was be VBD cord-014597-66vd2mdu 965 18 increased increase VBN cord-014597-66vd2mdu 965 19 by by IN cord-014597-66vd2mdu 965 20 glucose glucose NN cord-014597-66vd2mdu 965 21 increase increase NN cord-014597-66vd2mdu 965 22 , , , cord-014597-66vd2mdu 965 23 independent independent JJ cord-014597-66vd2mdu 965 24 of of IN cord-014597-66vd2mdu 965 25 the the DT cord-014597-66vd2mdu 965 26 culture culture NN cord-014597-66vd2mdu 965 27 temperature temperature NN cord-014597-66vd2mdu 965 28 used use VBN cord-014597-66vd2mdu 965 29 . . . cord-014597-66vd2mdu 966 1 While while IN cord-014597-66vd2mdu 966 2 at at IN cord-014597-66vd2mdu 966 3 33 33 CD cord-014597-66vd2mdu 966 4 ° ° NN cord-014597-66vd2mdu 966 5 C/0.018(h C/0.018(h NNP cord-014597-66vd2mdu 966 6 -1 -1 NN cord-014597-66vd2mdu 966 7 ) ) -RRB- cord-014597-66vd2mdu 967 1 the the DT cord-014597-66vd2mdu 967 2 q q NNP cord-014597-66vd2mdu 967 3 Lac Lac NNP cord-014597-66vd2mdu 967 4 decreased decrease VBD cord-014597-66vd2mdu 967 5 with with IN cord-014597-66vd2mdu 967 6 increasing increase VBG cord-014597-66vd2mdu 967 7 glucose glucose NN cord-014597-66vd2mdu 967 8 concentration concentration NN cord-014597-66vd2mdu 967 9 and and CC cord-014597-66vd2mdu 967 10 at at IN cord-014597-66vd2mdu 967 11 37 37 CD cord-014597-66vd2mdu 967 12 ° ° NN cord-014597-66vd2mdu 967 13 C/0.018(h C/0.018(h NNP cord-014597-66vd2mdu 967 14 -1 -1 NN cord-014597-66vd2mdu 967 15 ) ) -RRB- cord-014597-66vd2mdu 968 1 a a DT cord-014597-66vd2mdu 968 2 maximum maximum JJ cord-014597-66vd2mdu 968 3 consumption consumption NN cord-014597-66vd2mdu 968 4 was be VBD cord-014597-66vd2mdu 968 5 observed observe VBN cord-014597-66vd2mdu 968 6 at at IN cord-014597-66vd2mdu 968 7 30 30 CD cord-014597-66vd2mdu 968 8 mM mm CD cord-014597-66vd2mdu 968 9 glucose glucose NN cord-014597-66vd2mdu 968 10 ( ( -LRB- cord-014597-66vd2mdu 968 11 Fig Fig NNP cord-014597-66vd2mdu 968 12 . . . cord-014597-66vd2mdu 968 13 1d 1d CD cord-014597-66vd2mdu 968 14 ) ) -RRB- cord-014597-66vd2mdu 968 15 . . . cord-014597-66vd2mdu 969 1 The the DT cord-014597-66vd2mdu 969 2 lactate lactate NN cord-014597-66vd2mdu 969 3 - - HYPH cord-014597-66vd2mdu 969 4 glucose glucose NN cord-014597-66vd2mdu 969 5 yield yield NN cord-014597-66vd2mdu 969 6 ( ( -LRB- cord-014597-66vd2mdu 969 7 Fig Fig NNP cord-014597-66vd2mdu 969 8 . . . cord-014597-66vd2mdu 969 9 1e 1e LS cord-014597-66vd2mdu 969 10 ) ) -RRB- cord-014597-66vd2mdu 969 11 not not RB cord-014597-66vd2mdu 969 12 showed show VBD cord-014597-66vd2mdu 969 13 relevant relevant JJ cord-014597-66vd2mdu 969 14 changes change NNS cord-014597-66vd2mdu 969 15 at at IN cord-014597-66vd2mdu 969 16 0.010(h 0.010(h CD cord-014597-66vd2mdu 969 17 -1 -1 CD cord-014597-66vd2mdu 969 18 ) ) -RRB- cord-014597-66vd2mdu 969 19 , , , cord-014597-66vd2mdu 969 20 while while IN cord-014597-66vd2mdu 969 21 at at IN cord-014597-66vd2mdu 969 22 0.018(h 0.018(h CD cord-014597-66vd2mdu 969 23 -1 -1 NN cord-014597-66vd2mdu 969 24 ) ) -RRB- cord-014597-66vd2mdu 970 1 this this DT cord-014597-66vd2mdu 970 2 yield yield NN cord-014597-66vd2mdu 970 3 showed show VBD cord-014597-66vd2mdu 970 4 a a DT cord-014597-66vd2mdu 970 5 more more RBR cord-014597-66vd2mdu 970 6 efficient efficient JJ cord-014597-66vd2mdu 970 7 utilization utilization NN cord-014597-66vd2mdu 970 8 of of IN cord-014597-66vd2mdu 970 9 glucose glucose NN cord-014597-66vd2mdu 970 10 , , , cord-014597-66vd2mdu 970 11 as as IN cord-014597-66vd2mdu 970 12 glucose glucose NN cord-014597-66vd2mdu 970 13 concentration concentration NN cord-014597-66vd2mdu 970 14 was be VBD cord-014597-66vd2mdu 970 15 increased increase VBN cord-014597-66vd2mdu 970 16 . . . cord-014597-66vd2mdu 971 1 However however RB cord-014597-66vd2mdu 971 2 , , , cord-014597-66vd2mdu 971 3 this this DT cord-014597-66vd2mdu 971 4 last last JJ cord-014597-66vd2mdu 971 5 behaviour behaviour NN cord-014597-66vd2mdu 971 6 was be VBD cord-014597-66vd2mdu 971 7 not not RB cord-014597-66vd2mdu 971 8 reflected reflect VBN cord-014597-66vd2mdu 971 9 in in IN cord-014597-66vd2mdu 971 10 an an DT cord-014597-66vd2mdu 971 11 increase increase NN cord-014597-66vd2mdu 971 12 of of IN cord-014597-66vd2mdu 971 13 r r NN cord-014597-66vd2mdu 971 14 - - HYPH cord-014597-66vd2mdu 971 15 protein protein NN cord-014597-66vd2mdu 971 16 production production NN cord-014597-66vd2mdu 971 17 . . . cord-014597-66vd2mdu 972 1 The the DT cord-014597-66vd2mdu 972 2 concentration concentration NN cord-014597-66vd2mdu 972 3 of of IN cord-014597-66vd2mdu 972 4 glucose glucose NN cord-014597-66vd2mdu 972 5 has have VBZ cord-014597-66vd2mdu 972 6 the the DT cord-014597-66vd2mdu 972 7 greatest great JJS cord-014597-66vd2mdu 972 8 impact impact NN cord-014597-66vd2mdu 972 9 on on IN cord-014597-66vd2mdu 972 10 the the DT cord-014597-66vd2mdu 972 11 behaviour behaviour NN cord-014597-66vd2mdu 972 12 of of IN cord-014597-66vd2mdu 972 13 the the DT cord-014597-66vd2mdu 972 14 culture culture NN cord-014597-66vd2mdu 972 15 , , , cord-014597-66vd2mdu 972 16 and and CC cord-014597-66vd2mdu 972 17 its -PRON- PRP$ cord-014597-66vd2mdu 972 18 increase increase NN cord-014597-66vd2mdu 972 19 affects affect VBZ cord-014597-66vd2mdu 972 20 positively positively RB cord-014597-66vd2mdu 972 21 the the DT cord-014597-66vd2mdu 972 22 protein protein NN cord-014597-66vd2mdu 972 23 productivity productivity NN cord-014597-66vd2mdu 972 24 . . . cord-014597-66vd2mdu 973 1 The the DT cord-014597-66vd2mdu 973 2 MH MH NNP cord-014597-66vd2mdu 973 3 did do VBD cord-014597-66vd2mdu 973 4 not not RB cord-014597-66vd2mdu 973 5 improve improve VB cord-014597-66vd2mdu 973 6 proteins protein NNS cord-014597-66vd2mdu 973 7 productivity productivity NN cord-014597-66vd2mdu 973 8 of of IN cord-014597-66vd2mdu 973 9 CHO CHO NNP cord-014597-66vd2mdu 973 10 cells cell NNS cord-014597-66vd2mdu 973 11 producing produce VBG cord-014597-66vd2mdu 973 12 tPA tPA NNP cord-014597-66vd2mdu 973 13 under under IN cord-014597-66vd2mdu 973 14 the the DT cord-014597-66vd2mdu 973 15 different different JJ cord-014597-66vd2mdu 973 16 conditions condition NNS cord-014597-66vd2mdu 973 17 evaluated evaluate VBN cord-014597-66vd2mdu 973 18 ; ; : cord-014597-66vd2mdu 973 19 low low JJ cord-014597-66vd2mdu 973 20 dilution dilution NN cord-014597-66vd2mdu 973 21 rate rate NN cord-014597-66vd2mdu 973 22 and and CC cord-014597-66vd2mdu 973 23 at at IN cord-014597-66vd2mdu 973 24 high high JJ cord-014597-66vd2mdu 973 25 glucose glucose NN cord-014597-66vd2mdu 973 26 concentration concentration NN cord-014597-66vd2mdu 973 27 impact impact NN cord-014597-66vd2mdu 973 28 positively positively RB cord-014597-66vd2mdu 973 29 the the DT cord-014597-66vd2mdu 973 30 protein protein NN cord-014597-66vd2mdu 973 31 productivity productivity NN cord-014597-66vd2mdu 973 32 and and CC cord-014597-66vd2mdu 973 33 the the DT cord-014597-66vd2mdu 973 34 metabolism metabolism NN cord-014597-66vd2mdu 973 35 exhibited exhibit VBN cord-014597-66vd2mdu 973 36 by by IN cord-014597-66vd2mdu 973 37 the the DT cord-014597-66vd2mdu 973 38 cells cell NNS cord-014597-66vd2mdu 973 39 . . . cord-014597-66vd2mdu 974 1 Background background NN cord-014597-66vd2mdu 974 2 Mammalian mammalian JJ cord-014597-66vd2mdu 974 3 cell cell NN cord-014597-66vd2mdu 974 4 cultures culture NNS cord-014597-66vd2mdu 974 5 are be VBP cord-014597-66vd2mdu 974 6 the the DT cord-014597-66vd2mdu 974 7 most most RBS cord-014597-66vd2mdu 974 8 commonly commonly RB cord-014597-66vd2mdu 974 9 used use VBN cord-014597-66vd2mdu 974 10 bioprocess bioprocess NN cord-014597-66vd2mdu 974 11 for for IN cord-014597-66vd2mdu 974 12 the the DT cord-014597-66vd2mdu 974 13 production production NN cord-014597-66vd2mdu 974 14 of of IN cord-014597-66vd2mdu 974 15 therapeutic therapeutic JJ cord-014597-66vd2mdu 974 16 recombinant recombinant JJ cord-014597-66vd2mdu 974 17 proteins protein NNS cord-014597-66vd2mdu 974 18 such such JJ cord-014597-66vd2mdu 974 19 as as IN cord-014597-66vd2mdu 974 20 monoclonal monoclonal JJ cord-014597-66vd2mdu 974 21 antibodies antibody NNS cord-014597-66vd2mdu 974 22 ( ( -LRB- cord-014597-66vd2mdu 974 23 mAbs mAbs NNP cord-014597-66vd2mdu 974 24 ) ) -RRB- cord-014597-66vd2mdu 974 25 . . . cord-014597-66vd2mdu 975 1 Facing face VBG cord-014597-66vd2mdu 975 2 to to IN cord-014597-66vd2mdu 975 3 the the DT cord-014597-66vd2mdu 975 4 increasing increase VBG cord-014597-66vd2mdu 975 5 demand demand NN cord-014597-66vd2mdu 975 6 of of IN cord-014597-66vd2mdu 975 7 these these DT cord-014597-66vd2mdu 975 8 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 975 9 , , , cord-014597-66vd2mdu 975 10 the the DT cord-014597-66vd2mdu 975 11 FDA FDA NNP cord-014597-66vd2mdu 975 12 has have VBZ cord-014597-66vd2mdu 975 13 initiated initiate VBN cord-014597-66vd2mdu 975 14 the the DT cord-014597-66vd2mdu 975 15 Process Process NNP cord-014597-66vd2mdu 975 16 Analytical Analytical NNP cord-014597-66vd2mdu 975 17 Technology Technology NNP cord-014597-66vd2mdu 975 18 ( ( -LRB- cord-014597-66vd2mdu 975 19 PAT PAT NNP cord-014597-66vd2mdu 975 20 ) ) -RRB- cord-014597-66vd2mdu 975 21 framework framework NN cord-014597-66vd2mdu 975 22 in in IN cord-014597-66vd2mdu 975 23 order order NN cord-014597-66vd2mdu 975 24 to to TO cord-014597-66vd2mdu 975 25 encourage encourage VB cord-014597-66vd2mdu 975 26 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 975 27 industries industry NNS cord-014597-66vd2mdu 975 28 to to TO cord-014597-66vd2mdu 975 29 use use VB cord-014597-66vd2mdu 975 30 innovative innovative JJ cord-014597-66vd2mdu 975 31 technologies technology NNS cord-014597-66vd2mdu 975 32 to to TO cord-014597-66vd2mdu 975 33 monitor monitor VB cord-014597-66vd2mdu 975 34 in in IN cord-014597-66vd2mdu 975 35 real real JJ cord-014597-66vd2mdu 975 36 time time NN cord-014597-66vd2mdu 975 37 the the DT cord-014597-66vd2mdu 975 38 critical critical JJ cord-014597-66vd2mdu 975 39 process process NN cord-014597-66vd2mdu 975 40 parameters parameter NNS cord-014597-66vd2mdu 975 41 ( ( -LRB- cord-014597-66vd2mdu 975 42 CPPs CPPs NNPS cord-014597-66vd2mdu 975 43 ) ) -RRB- cord-014597-66vd2mdu 975 44 , , , cord-014597-66vd2mdu 975 45 and and CC cord-014597-66vd2mdu 975 46 to to TO cord-014597-66vd2mdu 975 47 ensure ensure VB cord-014597-66vd2mdu 975 48 the the DT cord-014597-66vd2mdu 975 49 final final JJ cord-014597-66vd2mdu 975 50 product product NN cord-014597-66vd2mdu 975 51 quality quality NN cord-014597-66vd2mdu 975 52 [ [ -LRB- cord-014597-66vd2mdu 975 53 1 1 CD cord-014597-66vd2mdu 975 54 ] ] -RRB- cord-014597-66vd2mdu 975 55 . . . cord-014597-66vd2mdu 976 1 One one CD cord-014597-66vd2mdu 976 2 of of IN cord-014597-66vd2mdu 976 3 the the DT cord-014597-66vd2mdu 976 4 most most RBS cord-014597-66vd2mdu 976 5 important important JJ cord-014597-66vd2mdu 976 6 CPPs cpp NNS cord-014597-66vd2mdu 976 7 for for IN cord-014597-66vd2mdu 976 8 cell cell NN cord-014597-66vd2mdu 976 9 culture culture NN cord-014597-66vd2mdu 976 10 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 976 11 is be VBZ cord-014597-66vd2mdu 976 12 the the DT cord-014597-66vd2mdu 976 13 specific specific JJ cord-014597-66vd2mdu 976 14 growth growth NN cord-014597-66vd2mdu 976 15 rate rate NN cord-014597-66vd2mdu 976 16 ( ( -LRB- cord-014597-66vd2mdu 976 17 μ μ NN cord-014597-66vd2mdu 976 18 ) ) -RRB- cord-014597-66vd2mdu 976 19 , , , cord-014597-66vd2mdu 976 20 which which WDT cord-014597-66vd2mdu 976 21 is be VBZ cord-014597-66vd2mdu 976 22 a a DT cord-014597-66vd2mdu 976 23 direct direct JJ cord-014597-66vd2mdu 976 24 indicator indicator NN cord-014597-66vd2mdu 976 25 of of IN cord-014597-66vd2mdu 976 26 cellular cellular JJ cord-014597-66vd2mdu 976 27 physiological physiological JJ cord-014597-66vd2mdu 976 28 state state NN cord-014597-66vd2mdu 976 29 . . . cord-014597-66vd2mdu 977 1 Indeed indeed RB cord-014597-66vd2mdu 977 2 , , , cord-014597-66vd2mdu 977 3 μ μ NN cord-014597-66vd2mdu 977 4 is be VBZ cord-014597-66vd2mdu 977 5 sensible sensible JJ cord-014597-66vd2mdu 977 6 to to IN cord-014597-66vd2mdu 977 7 culture culture NN cord-014597-66vd2mdu 977 8 conditions condition NNS cord-014597-66vd2mdu 977 9 and and CC cord-014597-66vd2mdu 977 10 its -PRON- PRP$ cord-014597-66vd2mdu 977 11 value value NN cord-014597-66vd2mdu 977 12 decreases decrease VBZ cord-014597-66vd2mdu 977 13 when when WRB cord-014597-66vd2mdu 977 14 cells cell NNS cord-014597-66vd2mdu 977 15 are be VBP cord-014597-66vd2mdu 977 16 in in IN cord-014597-66vd2mdu 977 17 the the DT cord-014597-66vd2mdu 977 18 unfavourable unfavourable JJ cord-014597-66vd2mdu 977 19 environment environment NN cord-014597-66vd2mdu 977 20 for for IN cord-014597-66vd2mdu 977 21 growth growth NN cord-014597-66vd2mdu 977 22 [ [ -LRB- cord-014597-66vd2mdu 977 23 2 2 CD cord-014597-66vd2mdu 977 24 ] ] -RRB- cord-014597-66vd2mdu 977 25 , , , cord-014597-66vd2mdu 977 26 which which WDT cord-014597-66vd2mdu 977 27 may may MD cord-014597-66vd2mdu 977 28 greatly greatly RB cord-014597-66vd2mdu 977 29 influence influence VB cord-014597-66vd2mdu 977 30 mAb mab NN cord-014597-66vd2mdu 977 31 production production NN cord-014597-66vd2mdu 977 32 and and CC cord-014597-66vd2mdu 977 33 quality quality NN cord-014597-66vd2mdu 977 34 . . . cord-014597-66vd2mdu 978 1 However however RB cord-014597-66vd2mdu 978 2 , , , cord-014597-66vd2mdu 978 3 until until IN cord-014597-66vd2mdu 978 4 this this DT cord-014597-66vd2mdu 978 5 day day NN cord-014597-66vd2mdu 978 6 , , , cord-014597-66vd2mdu 978 7 the the DT cord-014597-66vd2mdu 978 8 online online JJ cord-014597-66vd2mdu 978 9 monitoring monitoring NN cord-014597-66vd2mdu 978 10 of of IN cord-014597-66vd2mdu 978 11 μ μ NN cord-014597-66vd2mdu 978 12 remains remain VBZ cord-014597-66vd2mdu 978 13 a a DT cord-014597-66vd2mdu 978 14 great great JJ cord-014597-66vd2mdu 978 15 challenge challenge NN cord-014597-66vd2mdu 978 16 for for IN cord-014597-66vd2mdu 978 17 mammalian mammalian JJ cord-014597-66vd2mdu 978 18 cell cell NN cord-014597-66vd2mdu 978 19 culture culture NN cord-014597-66vd2mdu 978 20 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 978 21 . . . cord-014597-66vd2mdu 979 1 IgG IgG NNP cord-014597-66vd2mdu 979 2 - - HYPH cord-014597-66vd2mdu 979 3 producing produce VBG cord-014597-66vd2mdu 979 4 CHO CHO NNP cord-014597-66vd2mdu 979 5 cells cell NNS cord-014597-66vd2mdu 979 6 were be VBD cord-014597-66vd2mdu 979 7 cultured culture VBN cord-014597-66vd2mdu 979 8 in in IN cord-014597-66vd2mdu 979 9 2 2 CD cord-014597-66vd2mdu 979 10 L l NN cord-014597-66vd2mdu 979 11 stirred stir VBD cord-014597-66vd2mdu 979 12 bioreactors bioreactor NNS cord-014597-66vd2mdu 979 13 equipped equip VBN cord-014597-66vd2mdu 979 14 with with IN cord-014597-66vd2mdu 979 15 an an DT cord-014597-66vd2mdu 979 16 in in IN cord-014597-66vd2mdu 979 17 situ situ NN cord-014597-66vd2mdu 979 18 dielectric dielectric NN cord-014597-66vd2mdu 979 19 spectroscopy spectroscopy NN cord-014597-66vd2mdu 979 20 ( ( -LRB- cord-014597-66vd2mdu 979 21 Hamilton Hamilton NNP cord-014597-66vd2mdu 979 22 ) ) -RRB- cord-014597-66vd2mdu 979 23 . . . cord-014597-66vd2mdu 980 1 Operating operating NN cord-014597-66vd2mdu 980 2 conditions condition NNS cord-014597-66vd2mdu 980 3 were be VBD cord-014597-66vd2mdu 980 4 fixed fix VBN cord-014597-66vd2mdu 980 5 at at IN cord-014597-66vd2mdu 980 6 90 90 CD cord-014597-66vd2mdu 980 7 rpm rpm NN cord-014597-66vd2mdu 980 8 , , , cord-014597-66vd2mdu 980 9 50 50 CD cord-014597-66vd2mdu 980 10 % % NN cord-014597-66vd2mdu 980 11 of of IN cord-014597-66vd2mdu 980 12 air air NN cord-014597-66vd2mdu 980 13 saturation saturation NN cord-014597-66vd2mdu 980 14 , , , cord-014597-66vd2mdu 980 15 pH pH NNP cord-014597-66vd2mdu 980 16 7.2 7.2 CD cord-014597-66vd2mdu 980 17 and and CC cord-014597-66vd2mdu 980 18 37 37 CD cord-014597-66vd2mdu 980 19 ° ° NN cord-014597-66vd2mdu 980 20 C c NN cord-014597-66vd2mdu 980 21 . . . cord-014597-66vd2mdu 981 1 Permittivity permittivity NN cord-014597-66vd2mdu 981 2 of of IN cord-014597-66vd2mdu 981 3 cell cell NN cord-014597-66vd2mdu 981 4 culture culture NN cord-014597-66vd2mdu 981 5 was be VBD cord-014597-66vd2mdu 981 6 measured measure VBN cord-014597-66vd2mdu 981 7 every every DT cord-014597-66vd2mdu 981 8 12 12 CD cord-014597-66vd2mdu 981 9 min min NN cord-014597-66vd2mdu 981 10 , , , cord-014597-66vd2mdu 981 11 which which WDT cord-014597-66vd2mdu 981 12 allowed allow VBD cord-014597-66vd2mdu 981 13 to to TO cord-014597-66vd2mdu 981 14 calculate calculate VB cord-014597-66vd2mdu 981 15 in in IN cord-014597-66vd2mdu 981 16 real real JJ cord-014597-66vd2mdu 981 17 time time NN cord-014597-66vd2mdu 981 18 the the DT cord-014597-66vd2mdu 981 19 VCD vcd NN cord-014597-66vd2mdu 981 20 by by IN cord-014597-66vd2mdu 981 21 using use VBG cord-014597-66vd2mdu 981 22 a a DT cord-014597-66vd2mdu 981 23 previously previously RB cord-014597-66vd2mdu 981 24 established establish VBN cord-014597-66vd2mdu 981 25 linear linear JJ cord-014597-66vd2mdu 981 26 correlation correlation NN cord-014597-66vd2mdu 981 27 . . . cord-014597-66vd2mdu 982 1 Then then RB cord-014597-66vd2mdu 982 2 , , , cord-014597-66vd2mdu 982 3 a a DT cord-014597-66vd2mdu 982 4 model model NN cord-014597-66vd2mdu 982 5 of of IN cord-014597-66vd2mdu 982 6 online online JJ cord-014597-66vd2mdu 982 7 estimation estimation NN cord-014597-66vd2mdu 982 8 of of IN cord-014597-66vd2mdu 982 9 μ μ NN cord-014597-66vd2mdu 982 10 was be VBD cord-014597-66vd2mdu 982 11 developed develop VBN cord-014597-66vd2mdu 982 12 based base VBN cord-014597-66vd2mdu 982 13 on on IN cord-014597-66vd2mdu 982 14 VCD vcd NN cord-014597-66vd2mdu 982 15 prediction prediction NN cord-014597-66vd2mdu 982 16 and and CC cord-014597-66vd2mdu 982 17 cell cell NN cord-014597-66vd2mdu 982 18 mass mass NN cord-014597-66vd2mdu 982 19 balance balance NN cord-014597-66vd2mdu 982 20 equations equation NNS cord-014597-66vd2mdu 982 21 . . . cord-014597-66vd2mdu 983 1 Several several JJ cord-014597-66vd2mdu 983 2 signal signal NN cord-014597-66vd2mdu 983 3 noise noise NN cord-014597-66vd2mdu 983 4 filters filter NNS cord-014597-66vd2mdu 983 5 and and CC cord-014597-66vd2mdu 983 6 various various JJ cord-014597-66vd2mdu 983 7 calculation calculation NN cord-014597-66vd2mdu 983 8 methods method NNS cord-014597-66vd2mdu 983 9 were be VBD cord-014597-66vd2mdu 983 10 evaluated evaluate VBN cord-014597-66vd2mdu 983 11 to to TO cord-014597-66vd2mdu 983 12 reach reach VB cord-014597-66vd2mdu 983 13 better well JJR cord-014597-66vd2mdu 983 14 model model NN cord-014597-66vd2mdu 983 15 stability stability NN cord-014597-66vd2mdu 983 16 . . . cord-014597-66vd2mdu 984 1 Cell cell NN cord-014597-66vd2mdu 984 2 cultures culture NNS cord-014597-66vd2mdu 984 3 were be VBD cord-014597-66vd2mdu 984 4 performed perform VBN cord-014597-66vd2mdu 984 5 in in IN cord-014597-66vd2mdu 984 6 both both DT cord-014597-66vd2mdu 984 7 batch batch NN cord-014597-66vd2mdu 984 8 and and CC cord-014597-66vd2mdu 984 9 feed feed NN cord-014597-66vd2mdu 984 10 - - HYPH cord-014597-66vd2mdu 984 11 harvest harvest NN cord-014597-66vd2mdu 984 12 modes mode NNS cord-014597-66vd2mdu 984 13 . . . cord-014597-66vd2mdu 985 1 Feed feed NN cord-014597-66vd2mdu 985 2 - - HYPH cord-014597-66vd2mdu 985 3 harvest harvest NN cord-014597-66vd2mdu 985 4 cultures culture NNS cord-014597-66vd2mdu 985 5 consisted consist VBN cord-014597-66vd2mdu 985 6 of of IN cord-014597-66vd2mdu 985 7 sequential sequential JJ cord-014597-66vd2mdu 985 8 renewals renewal NNS cord-014597-66vd2mdu 985 9 of of IN cord-014597-66vd2mdu 985 10 2/3 2/3 CD cord-014597-66vd2mdu 985 11 volume volume NN cord-014597-66vd2mdu 985 12 of of IN cord-014597-66vd2mdu 985 13 the the DT cord-014597-66vd2mdu 985 14 culture culture NN cord-014597-66vd2mdu 985 15 medium medium NN cord-014597-66vd2mdu 985 16 by by IN cord-014597-66vd2mdu 985 17 following follow VBG cord-014597-66vd2mdu 985 18 different different JJ cord-014597-66vd2mdu 985 19 strategies strategy NNS cord-014597-66vd2mdu 985 20 . . . cord-014597-66vd2mdu 986 1 This this DT cord-014597-66vd2mdu 986 2 study study NN cord-014597-66vd2mdu 986 3 proposed propose VBD cord-014597-66vd2mdu 986 4 an an DT cord-014597-66vd2mdu 986 5 innovative innovative JJ cord-014597-66vd2mdu 986 6 methodology methodology NN cord-014597-66vd2mdu 986 7 based base VBN cord-014597-66vd2mdu 986 8 on on IN cord-014597-66vd2mdu 986 9 dielectric dielectric JJ cord-014597-66vd2mdu 986 10 spectroscopy spectroscopy NN cord-014597-66vd2mdu 986 11 to to TO cord-014597-66vd2mdu 986 12 monitor monitor VB cord-014597-66vd2mdu 986 13 in in IN cord-014597-66vd2mdu 986 14 real real JJ cord-014597-66vd2mdu 986 15 time time NN cord-014597-66vd2mdu 986 16 the the DT cord-014597-66vd2mdu 986 17 cellular cellular JJ cord-014597-66vd2mdu 986 18 physiological physiological JJ cord-014597-66vd2mdu 986 19 state state NN cord-014597-66vd2mdu 986 20 , , , cord-014597-66vd2mdu 986 21 by by IN cord-014597-66vd2mdu 986 22 online online JJ cord-014597-66vd2mdu 986 23 estimating estimate VBG cord-014597-66vd2mdu 986 24 the the DT cord-014597-66vd2mdu 986 25 specific specific JJ cord-014597-66vd2mdu 986 26 growth growth NN cord-014597-66vd2mdu 986 27 rate rate NN cord-014597-66vd2mdu 986 28 ( ( -LRB- cord-014597-66vd2mdu 986 29 μ μ NN cord-014597-66vd2mdu 986 30 ) ) -RRB- cord-014597-66vd2mdu 986 31 of of IN cord-014597-66vd2mdu 986 32 cells cell NNS cord-014597-66vd2mdu 986 33 . . . cord-014597-66vd2mdu 987 1 Model model NN cord-014597-66vd2mdu 987 2 of of IN cord-014597-66vd2mdu 987 3 online online JJ cord-014597-66vd2mdu 987 4 estimation estimation NN cord-014597-66vd2mdu 987 5 of of IN cord-014597-66vd2mdu 987 6 μ μ NN cord-014597-66vd2mdu 987 7 was be VBD cord-014597-66vd2mdu 987 8 developed develop VBN cord-014597-66vd2mdu 987 9 from from IN cord-014597-66vd2mdu 987 10 cultures culture NNS cord-014597-66vd2mdu 987 11 in in IN cord-014597-66vd2mdu 987 12 batch batch NN cord-014597-66vd2mdu 987 13 mode mode NN cord-014597-66vd2mdu 987 14 , , , cord-014597-66vd2mdu 987 15 and and CC cord-014597-66vd2mdu 987 16 was be VBD cord-014597-66vd2mdu 987 17 validated validate VBN cord-014597-66vd2mdu 987 18 by by IN cord-014597-66vd2mdu 987 19 comparing compare VBG cord-014597-66vd2mdu 987 20 online online RB cord-014597-66vd2mdu 987 21 estimated estimate VBN cord-014597-66vd2mdu 987 22 μ μ NN cord-014597-66vd2mdu 987 23 with with IN cord-014597-66vd2mdu 987 24 the the DT cord-014597-66vd2mdu 987 25 experimental experimental JJ cord-014597-66vd2mdu 987 26 ones one NNS cord-014597-66vd2mdu 987 27 calculated calculate VBN cord-014597-66vd2mdu 987 28 at at IN cord-014597-66vd2mdu 987 29 the the DT cord-014597-66vd2mdu 987 30 end end NN cord-014597-66vd2mdu 987 31 of of IN cord-014597-66vd2mdu 987 32 the the DT cord-014597-66vd2mdu 987 33 culture culture NN cord-014597-66vd2mdu 987 34 . . . cord-014597-66vd2mdu 988 1 With with IN cord-014597-66vd2mdu 988 2 this this DT cord-014597-66vd2mdu 988 3 model model NN cord-014597-66vd2mdu 988 4 , , , cord-014597-66vd2mdu 988 5 the the DT cord-014597-66vd2mdu 988 6 moment moment NN cord-014597-66vd2mdu 988 7 when when WRB cord-014597-66vd2mdu 988 8 μ μ NNP cord-014597-66vd2mdu 988 9 started start VBD cord-014597-66vd2mdu 988 10 to to TO cord-014597-66vd2mdu 988 11 decrease decrease VB cord-014597-66vd2mdu 988 12 significantly significantly RB cord-014597-66vd2mdu 988 13 , , , cord-014597-66vd2mdu 988 14 which which WDT cord-014597-66vd2mdu 988 15 indicated indicate VBD cord-014597-66vd2mdu 988 16 that that IN cord-014597-66vd2mdu 988 17 cells cell NNS cord-014597-66vd2mdu 988 18 were be VBD cord-014597-66vd2mdu 988 19 no no RB cord-014597-66vd2mdu 988 20 longer long RBR cord-014597-66vd2mdu 988 21 in in IN cord-014597-66vd2mdu 988 22 the the DT cord-014597-66vd2mdu 988 23 exponential exponential JJ cord-014597-66vd2mdu 988 24 growth growth NN cord-014597-66vd2mdu 988 25 phase phase NN cord-014597-66vd2mdu 988 26 , , , cord-014597-66vd2mdu 988 27 was be VBD cord-014597-66vd2mdu 988 28 identified identify VBN cord-014597-66vd2mdu 988 29 as as IN cord-014597-66vd2mdu 988 30 the the DT cord-014597-66vd2mdu 988 31 critical critical JJ cord-014597-66vd2mdu 988 32 moment moment NN cord-014597-66vd2mdu 988 33 . . . cord-014597-66vd2mdu 989 1 To to TO cord-014597-66vd2mdu 989 2 demonstrate demonstrate VB cord-014597-66vd2mdu 989 3 the the DT cord-014597-66vd2mdu 989 4 interest interest NN cord-014597-66vd2mdu 989 5 of of IN cord-014597-66vd2mdu 989 6 online online JJ cord-014597-66vd2mdu 989 7 estimation estimation NN cord-014597-66vd2mdu 989 8 of of IN cord-014597-66vd2mdu 989 9 μ μ NN cord-014597-66vd2mdu 989 10 , , , cord-014597-66vd2mdu 989 11 the the DT cord-014597-66vd2mdu 989 12 developed develop VBN cord-014597-66vd2mdu 989 13 model model NN cord-014597-66vd2mdu 989 14 was be VBD cord-014597-66vd2mdu 989 15 applied apply VBN cord-014597-66vd2mdu 989 16 to to IN cord-014597-66vd2mdu 989 17 a a DT cord-014597-66vd2mdu 989 18 feedharvest feedharv JJS cord-014597-66vd2mdu 989 19 culture culture NN cord-014597-66vd2mdu 989 20 , , , cord-014597-66vd2mdu 989 21 where where WRB cord-014597-66vd2mdu 989 22 the the DT cord-014597-66vd2mdu 989 23 medium medium JJ cord-014597-66vd2mdu 989 24 renewals renewal NNS cord-014597-66vd2mdu 989 25 were be VBD cord-014597-66vd2mdu 989 26 performed perform VBN cord-014597-66vd2mdu 989 27 at at IN cord-014597-66vd2mdu 989 28 the the DT cord-014597-66vd2mdu 989 29 critical critical JJ cord-014597-66vd2mdu 989 30 moments moment NNS cord-014597-66vd2mdu 989 31 indicated indicate VBN cord-014597-66vd2mdu 989 32 by by IN cord-014597-66vd2mdu 989 33 the the DT cord-014597-66vd2mdu 989 34 model model NN cord-014597-66vd2mdu 989 35 . . . cord-014597-66vd2mdu 990 1 This this DT cord-014597-66vd2mdu 990 2 culture culture NN cord-014597-66vd2mdu 990 3 was be VBD cord-014597-66vd2mdu 990 4 then then RB cord-014597-66vd2mdu 990 5 compared compare VBN cord-014597-66vd2mdu 990 6 with with IN cord-014597-66vd2mdu 990 7 the the DT cord-014597-66vd2mdu 990 8 traditional traditional JJ cord-014597-66vd2mdu 990 9 feed feed NN cord-014597-66vd2mdu 990 10 - - HYPH cord-014597-66vd2mdu 990 11 harvest harvest NN cord-014597-66vd2mdu 990 12 culture culture NN cord-014597-66vd2mdu 990 13 where where WRB cord-014597-66vd2mdu 990 14 medium medium JJ cord-014597-66vd2mdu 990 15 renewals renewal NNS cord-014597-66vd2mdu 990 16 were be VBD cord-014597-66vd2mdu 990 17 performed perform VBN cord-014597-66vd2mdu 990 18 by by IN cord-014597-66vd2mdu 990 19 following follow VBG cord-014597-66vd2mdu 990 20 offline offline JJ cord-014597-66vd2mdu 990 21 measurements measurement NNS cord-014597-66vd2mdu 990 22 of of IN cord-014597-66vd2mdu 990 23 glucose glucose NN cord-014597-66vd2mdu 990 24 and and CC cord-014597-66vd2mdu 990 25 glutamine glutamine NN cord-014597-66vd2mdu 990 26 . . . cord-014597-66vd2mdu 991 1 We -PRON- PRP cord-014597-66vd2mdu 991 2 found find VBD cord-014597-66vd2mdu 991 3 that that IN cord-014597-66vd2mdu 991 4 the the DT cord-014597-66vd2mdu 991 5 online online JJ cord-014597-66vd2mdu 991 6 strategy strategy NN cord-014597-66vd2mdu 991 7 allowed allow VBN cord-014597-66vd2mdu 991 8 to to TO cord-014597-66vd2mdu 991 9 maintain maintain VB cord-014597-66vd2mdu 991 10 the the DT cord-014597-66vd2mdu 991 11 value value NN cord-014597-66vd2mdu 991 12 of of IN cord-014597-66vd2mdu 991 13 μ μ NN cord-014597-66vd2mdu 991 14 by by IN cord-014597-66vd2mdu 991 15 renewing renew VBG cord-014597-66vd2mdu 991 16 the the DT cord-014597-66vd2mdu 991 17 medium medium NN cord-014597-66vd2mdu 991 18 at at IN cord-014597-66vd2mdu 991 19 the the DT cord-014597-66vd2mdu 991 20 right right JJ cord-014597-66vd2mdu 991 21 time time NN cord-014597-66vd2mdu 991 22 , , , cord-014597-66vd2mdu 991 23 while while IN cord-014597-66vd2mdu 991 24 the the DT cord-014597-66vd2mdu 991 25 values value NNS cord-014597-66vd2mdu 991 26 of of IN cord-014597-66vd2mdu 991 27 μ μ NN cord-014597-66vd2mdu 991 28 varied vary VBD cord-014597-66vd2mdu 991 29 a a DT cord-014597-66vd2mdu 991 30 lot lot NN cord-014597-66vd2mdu 991 31 when when WRB cord-014597-66vd2mdu 991 32 using use VBG cord-014597-66vd2mdu 991 33 offline offline JJ cord-014597-66vd2mdu 991 34 strategy strategy NN cord-014597-66vd2mdu 991 35 . . . cord-014597-66vd2mdu 992 1 Moreover moreover RB cord-014597-66vd2mdu 992 2 , , , cord-014597-66vd2mdu 992 3 by by IN cord-014597-66vd2mdu 992 4 using use VBG cord-014597-66vd2mdu 992 5 the the DT cord-014597-66vd2mdu 992 6 online online JJ cord-014597-66vd2mdu 992 7 estimation estimation NN cord-014597-66vd2mdu 992 8 of of IN cord-014597-66vd2mdu 992 9 μ μ NN cord-014597-66vd2mdu 992 10 , , , cord-014597-66vd2mdu 992 11 the the DT cord-014597-66vd2mdu 992 12 glycosylation glycosylation NN cord-014597-66vd2mdu 992 13 of of IN cord-014597-66vd2mdu 992 14 IgG igg NN cord-014597-66vd2mdu 992 15 was be VBD cord-014597-66vd2mdu 992 16 kept keep VBN cord-014597-66vd2mdu 992 17 at at IN cord-014597-66vd2mdu 992 18 a a DT cord-014597-66vd2mdu 992 19 high high JJ cord-014597-66vd2mdu 992 20 level level NN cord-014597-66vd2mdu 992 21 ( ( -LRB- cord-014597-66vd2mdu 992 22 about about RB cord-014597-66vd2mdu 992 23 95 95 CD cord-014597-66vd2mdu 992 24 % % NN cord-014597-66vd2mdu 992 25 ) ) -RRB- cord-014597-66vd2mdu 992 26 throughout throughout IN cord-014597-66vd2mdu 992 27 the the DT cord-014597-66vd2mdu 992 28 whole whole JJ cord-014597-66vd2mdu 992 29 culture culture NN cord-014597-66vd2mdu 992 30 . . . cord-014597-66vd2mdu 993 1 However however RB cord-014597-66vd2mdu 993 2 , , , cord-014597-66vd2mdu 993 3 for for IN cord-014597-66vd2mdu 993 4 the the DT cord-014597-66vd2mdu 993 5 culture culture NN cord-014597-66vd2mdu 993 6 using use VBG cord-014597-66vd2mdu 993 7 offline offline JJ cord-014597-66vd2mdu 993 8 strategy strategy NN cord-014597-66vd2mdu 993 9 , , , cord-014597-66vd2mdu 993 10 the the DT cord-014597-66vd2mdu 993 11 glycosylation glycosylation NN cord-014597-66vd2mdu 993 12 level level NN cord-014597-66vd2mdu 993 13 decreased decrease VBD cord-014597-66vd2mdu 993 14 progressively progressively RB cord-014597-66vd2mdu 993 15 and and CC cord-014597-66vd2mdu 993 16 was be VBD cord-014597-66vd2mdu 993 17 only only RB cord-014597-66vd2mdu 993 18 about about RB cord-014597-66vd2mdu 993 19 75 75 CD cord-014597-66vd2mdu 993 20 % % NN cord-014597-66vd2mdu 993 21 at at IN cord-014597-66vd2mdu 993 22 the the DT cord-014597-66vd2mdu 993 23 end end NN cord-014597-66vd2mdu 993 24 of of IN cord-014597-66vd2mdu 993 25 the the DT cord-014597-66vd2mdu 993 26 culture culture NN cord-014597-66vd2mdu 993 27 ( ( -LRB- cord-014597-66vd2mdu 993 28 Fig Fig NNP cord-014597-66vd2mdu 993 29 . . . cord-014597-66vd2mdu 993 30 1 1 CD cord-014597-66vd2mdu 993 31 ) ) -RRB- cord-014597-66vd2mdu 993 32 . . . cord-014597-66vd2mdu 994 1 Model model NN cord-014597-66vd2mdu 994 2 of of IN cord-014597-66vd2mdu 994 3 online online JJ cord-014597-66vd2mdu 994 4 estimation estimation NN cord-014597-66vd2mdu 994 5 of of IN cord-014597-66vd2mdu 994 6 μ μ NN cord-014597-66vd2mdu 994 7 was be VBD cord-014597-66vd2mdu 994 8 developed develop VBN cord-014597-66vd2mdu 994 9 by by IN cord-014597-66vd2mdu 994 10 using use VBG cord-014597-66vd2mdu 994 11 dielectric dielectric NN cord-014597-66vd2mdu 994 12 spectroscopy spectroscopy NN cord-014597-66vd2mdu 994 13 , , , cord-014597-66vd2mdu 994 14 which which WDT cord-014597-66vd2mdu 994 15 allowed allow VBD cord-014597-66vd2mdu 994 16 to to TO cord-014597-66vd2mdu 994 17 monitor monitor VB cord-014597-66vd2mdu 994 18 the the DT cord-014597-66vd2mdu 994 19 physiological physiological JJ cord-014597-66vd2mdu 994 20 state state NN cord-014597-66vd2mdu 994 21 of of IN cord-014597-66vd2mdu 994 22 cells cell NNS cord-014597-66vd2mdu 994 23 in in IN cord-014597-66vd2mdu 994 24 cell cell NN cord-014597-66vd2mdu 994 25 culture culture NN cord-014597-66vd2mdu 994 26 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 994 27 . . . cord-014597-66vd2mdu 995 1 Implementation implementation NN cord-014597-66vd2mdu 995 2 of of IN cord-014597-66vd2mdu 995 3 this this DT cord-014597-66vd2mdu 995 4 model model NN cord-014597-66vd2mdu 995 5 in in IN cord-014597-66vd2mdu 995 6 feed feed NN cord-014597-66vd2mdu 995 7 - - HYPH cord-014597-66vd2mdu 995 8 harvest harvest NN cord-014597-66vd2mdu 995 9 cell cell NN cord-014597-66vd2mdu 995 10 culture culture NN cord-014597-66vd2mdu 995 11 led lead VBD cord-014597-66vd2mdu 995 12 to to IN cord-014597-66vd2mdu 995 13 better well JJR cord-014597-66vd2mdu 995 14 mAb mab NN cord-014597-66vd2mdu 995 15 glycosylation glycosylation NN cord-014597-66vd2mdu 995 16 , , , cord-014597-66vd2mdu 995 17 which which WDT cord-014597-66vd2mdu 995 18 demonstrates demonstrate VBZ cord-014597-66vd2mdu 995 19 clearly clearly RB cord-014597-66vd2mdu 995 20 the the DT cord-014597-66vd2mdu 995 21 potential potential NN cord-014597-66vd2mdu 995 22 of of IN cord-014597-66vd2mdu 995 23 this this DT cord-014597-66vd2mdu 995 24 methodology methodology NN cord-014597-66vd2mdu 995 25 in in IN cord-014597-66vd2mdu 995 26 mAb mab NN cord-014597-66vd2mdu 995 27 production production NN cord-014597-66vd2mdu 995 28 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 995 29 . . . cord-014597-66vd2mdu 996 1 Background Background NNP cord-014597-66vd2mdu 996 2 Monoclonal monoclonal JJ cord-014597-66vd2mdu 996 3 antibodies antibody NNS cord-014597-66vd2mdu 996 4 are be VBP cord-014597-66vd2mdu 996 5 normally normally RB cord-014597-66vd2mdu 996 6 synthesised synthesise VBN cord-014597-66vd2mdu 996 7 from from IN cord-014597-66vd2mdu 996 8 transfected transfecte VBN cord-014597-66vd2mdu 996 9 mammalian mammalian JJ cord-014597-66vd2mdu 996 10 cells cell NNS cord-014597-66vd2mdu 996 11 as as IN cord-014597-66vd2mdu 996 12 heterogeneous heterogeneous JJ cord-014597-66vd2mdu 996 13 mixtures mixture NNS cord-014597-66vd2mdu 996 14 of of IN cord-014597-66vd2mdu 996 15 glycoforms glycoform NNS cord-014597-66vd2mdu 996 16 [ [ -LRB- cord-014597-66vd2mdu 996 17 1 1 CD cord-014597-66vd2mdu 996 18 ] ] -RRB- cord-014597-66vd2mdu 996 19 . . . cord-014597-66vd2mdu 997 1 However however RB cord-014597-66vd2mdu 997 2 , , , cord-014597-66vd2mdu 997 3 clinical clinical JJ cord-014597-66vd2mdu 997 4 efficacy efficacy NN cord-014597-66vd2mdu 997 5 may may MD cord-014597-66vd2mdu 997 6 depend depend VB cord-014597-66vd2mdu 997 7 upon upon IN cord-014597-66vd2mdu 997 8 single single JJ cord-014597-66vd2mdu 997 9 glycoforms glycoform NNS cord-014597-66vd2mdu 997 10 which which WDT cord-014597-66vd2mdu 997 11 have have VBP cord-014597-66vd2mdu 997 12 been be VBN cord-014597-66vd2mdu 997 13 difficult difficult JJ cord-014597-66vd2mdu 997 14 to to TO cord-014597-66vd2mdu 997 15 isolate isolate VB cord-014597-66vd2mdu 997 16 [ [ -LRB- cord-014597-66vd2mdu 997 17 2 2 CD cord-014597-66vd2mdu 997 18 ] ] -RRB- cord-014597-66vd2mdu 997 19 . . . cord-014597-66vd2mdu 998 1 We -PRON- PRP cord-014597-66vd2mdu 998 2 have have VBP cord-014597-66vd2mdu 998 3 now now RB cord-014597-66vd2mdu 998 4 developed develop VBN cord-014597-66vd2mdu 998 5 an an DT cord-014597-66vd2mdu 998 6 efficient efficient JJ cord-014597-66vd2mdu 998 7 method method NN cord-014597-66vd2mdu 998 8 for for IN cord-014597-66vd2mdu 998 9 generating generate VBG cord-014597-66vd2mdu 998 10 single single JJ cord-014597-66vd2mdu 998 11 glycoforms glycoform NNS cord-014597-66vd2mdu 998 12 by by IN cord-014597-66vd2mdu 998 13 solid solid JJ cord-014597-66vd2mdu 998 14 phase phase NN cord-014597-66vd2mdu 998 15 re re NN cord-014597-66vd2mdu 998 16 - - NN cord-014597-66vd2mdu 998 17 modelling modelling NN cord-014597-66vd2mdu 998 18 which which WDT cord-014597-66vd2mdu 998 19 is be VBZ cord-014597-66vd2mdu 998 20 superior superior JJ cord-014597-66vd2mdu 998 21 to to IN cord-014597-66vd2mdu 998 22 previous previous JJ cord-014597-66vd2mdu 998 23 methods method NNS cord-014597-66vd2mdu 998 24 because because IN cord-014597-66vd2mdu 998 25 it -PRON- PRP cord-014597-66vd2mdu 998 26 allows allow VBZ cord-014597-66vd2mdu 998 27 a a DT cord-014597-66vd2mdu 998 28 sequential sequential JJ cord-014597-66vd2mdu 998 29 series series NN cord-014597-66vd2mdu 998 30 of of IN cord-014597-66vd2mdu 998 31 enzymatic enzymatic JJ cord-014597-66vd2mdu 998 32 changes change NNS cord-014597-66vd2mdu 998 33 without without IN cord-014597-66vd2mdu 998 34 the the DT cord-014597-66vd2mdu 998 35 need need NN cord-014597-66vd2mdu 998 36 for for IN cord-014597-66vd2mdu 998 37 intermediate intermediate JJ cord-014597-66vd2mdu 998 38 purification purification NN cord-014597-66vd2mdu 998 39 of of IN cord-014597-66vd2mdu 998 40 the the DT cord-014597-66vd2mdu 998 41 antibody antibody NN cord-014597-66vd2mdu 998 42 . . . cord-014597-66vd2mdu 999 1 Solidphase solidphase NN cord-014597-66vd2mdu 999 2 binding binding NN cord-014597-66vd2mdu 999 3 exposes expose VBZ cord-014597-66vd2mdu 999 4 the the DT cord-014597-66vd2mdu 999 5 antibody antibody NN cord-014597-66vd2mdu 999 6 glycans glycan NNS cord-014597-66vd2mdu 999 7 to to TO cord-014597-66vd2mdu 999 8 enable enable VB cord-014597-66vd2mdu 999 9 easier easy JJR cord-014597-66vd2mdu 999 10 access access NN cord-014597-66vd2mdu 999 11 of of IN cord-014597-66vd2mdu 999 12 the the DT cord-014597-66vd2mdu 999 13 transforming transform VBG cord-014597-66vd2mdu 999 14 glycosylation glycosylation NN cord-014597-66vd2mdu 999 15 enzyme enzyme NN cord-014597-66vd2mdu 999 16 . . . cord-014597-66vd2mdu 1000 1 The the DT cord-014597-66vd2mdu 1000 2 antibodies antibody NNS cord-014597-66vd2mdu 1000 3 subjected subject VBN cord-014597-66vd2mdu 1000 4 to to IN cord-014597-66vd2mdu 1000 5 modification modification NN cord-014597-66vd2mdu 1000 6 were be VBD cord-014597-66vd2mdu 1000 7 a a DT cord-014597-66vd2mdu 1000 8 chimeric chimeric JJ cord-014597-66vd2mdu 1000 9 human/ human/ CD cord-014597-66vd2mdu 1000 10 camelid camelid NN cord-014597-66vd2mdu 1000 11 monoclonal monoclonal JJ cord-014597-66vd2mdu 1000 12 antibody antibody NN cord-014597-66vd2mdu 1000 13 ( ( -LRB- cord-014597-66vd2mdu 1000 14 EG2 EG2 NNP cord-014597-66vd2mdu 1000 15 ) ) -RRB- cord-014597-66vd2mdu 1000 16 , , , cord-014597-66vd2mdu 1000 17 a a DT cord-014597-66vd2mdu 1000 18 humanized humanize VBN cord-014597-66vd2mdu 1000 19 monoclonal monoclonal JJ cord-014597-66vd2mdu 1000 20 antibody antibody NN cord-014597-66vd2mdu 1000 21 ( ( -LRB- cord-014597-66vd2mdu 1000 22 IL8 IL8 NNP cord-014597-66vd2mdu 1000 23 ) ) -RRB- cord-014597-66vd2mdu 1000 24 , , , cord-014597-66vd2mdu 1000 25 a a DT cord-014597-66vd2mdu 1000 26 full full JJ cord-014597-66vd2mdu 1000 27 size size NN cord-014597-66vd2mdu 1000 28 chimeric chimeric JJ cord-014597-66vd2mdu 1000 29 antibody antibody NN cord-014597-66vd2mdu 1000 30 ( ( -LRB- cord-014597-66vd2mdu 1000 31 Cetuximab Cetuximab NNP cord-014597-66vd2mdu 1000 32 ) ) -RRB- cord-014597-66vd2mdu 1000 33 and and CC cord-014597-66vd2mdu 1000 34 polyclonal polyclonal JJ cord-014597-66vd2mdu 1000 35 antibodies antibody NNS cord-014597-66vd2mdu 1000 36 obtained obtain VBN cord-014597-66vd2mdu 1000 37 from from IN cord-014597-66vd2mdu 1000 38 pooled pool VBN cord-014597-66vd2mdu 1000 39 human human JJ cord-014597-66vd2mdu 1000 40 serum serum NN cord-014597-66vd2mdu 1000 41 . . . cord-014597-66vd2mdu 1001 1 The the DT cord-014597-66vd2mdu 1001 2 antibodies antibody NNS cord-014597-66vd2mdu 1001 3 were be VBD cord-014597-66vd2mdu 1001 4 bound bind VBN cord-014597-66vd2mdu 1001 5 to to IN cord-014597-66vd2mdu 1001 6 a a DT cord-014597-66vd2mdu 1001 7 Protein Protein NNP cord-014597-66vd2mdu 1001 8 A a DT cord-014597-66vd2mdu 1001 9 column column NN cord-014597-66vd2mdu 1001 10 using use VBG cord-014597-66vd2mdu 1001 11 conditions condition NNS cord-014597-66vd2mdu 1001 12 typical typical JJ cord-014597-66vd2mdu 1001 13 of of IN cord-014597-66vd2mdu 1001 14 Mab Mab NNP cord-014597-66vd2mdu 1001 15 purification purification NN cord-014597-66vd2mdu 1001 16 ( ( -LRB- cord-014597-66vd2mdu 1001 17 Fig Fig NNP cord-014597-66vd2mdu 1001 18 . . . cord-014597-66vd2mdu 1001 19 1 1 CD cord-014597-66vd2mdu 1001 20 ) ) -RRB- cord-014597-66vd2mdu 1001 21 . . . cord-014597-66vd2mdu 1002 1 After after IN cord-014597-66vd2mdu 1002 2 washing wash VBG cord-014597-66vd2mdu 1002 3 out out RP cord-014597-66vd2mdu 1002 4 non non JJ cord-014597-66vd2mdu 1002 5 - - JJ cord-014597-66vd2mdu 1002 6 bound bound JJ cord-014597-66vd2mdu 1002 7 impurities impurity NNS cord-014597-66vd2mdu 1002 8 by by IN cord-014597-66vd2mdu 1002 9 a a DT cord-014597-66vd2mdu 1002 10 neutral neutral JJ cord-014597-66vd2mdu 1002 11 pH pH NNP cord-014597-66vd2mdu 1002 12 buffer buffer NN cord-014597-66vd2mdu 1002 13 , , , cord-014597-66vd2mdu 1002 14 each each DT cord-014597-66vd2mdu 1002 15 antibody antibody NN cord-014597-66vd2mdu 1002 16 was be VBD cord-014597-66vd2mdu 1002 17 subjected subject VBN cord-014597-66vd2mdu 1002 18 to to IN cord-014597-66vd2mdu 1002 19 enzymatic enzymatic JJ cord-014597-66vd2mdu 1002 20 modification modification NN cord-014597-66vd2mdu 1002 21 directed direct VBN cord-014597-66vd2mdu 1002 22 to to IN cord-014597-66vd2mdu 1002 23 a a DT cord-014597-66vd2mdu 1002 24 targeted target VBN cord-014597-66vd2mdu 1002 25 glycan glycan NN cord-014597-66vd2mdu 1002 26 profile profile NN cord-014597-66vd2mdu 1002 27 ( ( -LRB- cord-014597-66vd2mdu 1002 28 Table table NN cord-014597-66vd2mdu 1002 29 1 1 CD cord-014597-66vd2mdu 1002 30 ) ) -RRB- cord-014597-66vd2mdu 1002 31 . . . cord-014597-66vd2mdu 1003 1 The the DT cord-014597-66vd2mdu 1003 2 antibodies antibody NNS cord-014597-66vd2mdu 1003 3 were be VBD cord-014597-66vd2mdu 1003 4 then then RB cord-014597-66vd2mdu 1003 5 eluted elute VBN cord-014597-66vd2mdu 1003 6 with with IN cord-014597-66vd2mdu 1003 7 a a DT cord-014597-66vd2mdu 1003 8 low low JJ cord-014597-66vd2mdu 1003 9 pH ph NN cord-014597-66vd2mdu 1003 10 buffer buffer NN cord-014597-66vd2mdu 1003 11 and and CC cord-014597-66vd2mdu 1003 12 neutralized neutralize VBN cord-014597-66vd2mdu 1003 13 . . . cord-014597-66vd2mdu 1004 1 The the DT cord-014597-66vd2mdu 1004 2 glycan glycan NN cord-014597-66vd2mdu 1004 3 profiles profile NNS cord-014597-66vd2mdu 1004 4 were be VBD cord-014597-66vd2mdu 1004 5 analysed analyse VBN cord-014597-66vd2mdu 1004 6 following follow VBG cord-014597-66vd2mdu 1004 7 glycan glycan NN cord-014597-66vd2mdu 1004 8 removal removal NN cord-014597-66vd2mdu 1004 9 with with IN cord-014597-66vd2mdu 1004 10 PNGase PNGase NNP cord-014597-66vd2mdu 1004 11 F F NNP cord-014597-66vd2mdu 1004 12 , , , cord-014597-66vd2mdu 1004 13 labelling label VBG cord-014597-66vd2mdu 1004 14 with with IN cord-014597-66vd2mdu 1004 15 2-aminobenzamide 2-aminobenzamide CD cord-014597-66vd2mdu 1004 16 and and CC cord-014597-66vd2mdu 1004 17 separation separation NN cord-014597-66vd2mdu 1004 18 on on IN cord-014597-66vd2mdu 1004 19 a a DT cord-014597-66vd2mdu 1004 20 HILIC HILIC NNP cord-014597-66vd2mdu 1004 21 - - HYPH cord-014597-66vd2mdu 1004 22 HPLC HPLC NNP cord-014597-66vd2mdu 1004 23 column column NN cord-014597-66vd2mdu 1004 24 [ [ -LRB- cord-014597-66vd2mdu 1004 25 3 3 CD cord-014597-66vd2mdu 1004 26 ] ] -RRB- cord-014597-66vd2mdu 1004 27 . . . cord-014597-66vd2mdu 1005 1 Prior prior RB cord-014597-66vd2mdu 1005 2 to to IN cord-014597-66vd2mdu 1005 3 enzymatic enzymatic JJ cord-014597-66vd2mdu 1005 4 modification modification NN cord-014597-66vd2mdu 1005 5 glycan glycan NN cord-014597-66vd2mdu 1005 6 analysis analysis NN cord-014597-66vd2mdu 1005 7 of of IN cord-014597-66vd2mdu 1005 8 all all DT cord-014597-66vd2mdu 1005 9 4 4 CD cord-014597-66vd2mdu 1005 10 antibodies antibody NNS cord-014597-66vd2mdu 1005 11 showed show VBD cord-014597-66vd2mdu 1005 12 variable variable JJ cord-014597-66vd2mdu 1005 13 galactosylation galactosylation NN cord-014597-66vd2mdu 1005 14 and and CC cord-014597-66vd2mdu 1005 15 sialylation sialylation NN cord-014597-66vd2mdu 1005 16 typical typical JJ cord-014597-66vd2mdu 1005 17 of of IN cord-014597-66vd2mdu 1005 18 human human JJ cord-014597-66vd2mdu 1005 19 Abs abs NN cord-014597-66vd2mdu 1005 20 . . . cord-014597-66vd2mdu 1006 1 This this DT cord-014597-66vd2mdu 1006 2 included include VBD cord-014597-66vd2mdu 1006 3 a a DT cord-014597-66vd2mdu 1006 4 distribution distribution NN cord-014597-66vd2mdu 1006 5 of of IN cord-014597-66vd2mdu 1006 6 FG0 FG0 NNP cord-014597-66vd2mdu 1006 7 , , , cord-014597-66vd2mdu 1006 8 FG1 FG1 NNP cord-014597-66vd2mdu 1006 9 , , , cord-014597-66vd2mdu 1006 10 FG2 FG2 NNP cord-014597-66vd2mdu 1006 11 , , , cord-014597-66vd2mdu 1006 12 FS1 FS1 NNP cord-014597-66vd2mdu 1006 13 and and CC cord-014597-66vd2mdu 1006 14 FS2 FS2 NNP cord-014597-66vd2mdu 1006 15 with with IN cord-014597-66vd2mdu 1006 16 galactosylation galactosylation NN cord-014597-66vd2mdu 1006 17 indices index NNS cord-014597-66vd2mdu 1006 18 ranging range VBG cord-014597-66vd2mdu 1006 19 from from IN cord-014597-66vd2mdu 1006 20 0.22 0.22 CD cord-014597-66vd2mdu 1006 21 for for IN cord-014597-66vd2mdu 1006 22 IL8 il8 NN cord-014597-66vd2mdu 1006 23 to to IN cord-014597-66vd2mdu 1006 24 0.64 0.64 CD cord-014597-66vd2mdu 1006 25 for for IN cord-014597-66vd2mdu 1006 26 EG2 EG2 NNP cord-014597-66vd2mdu 1006 27 . . . cord-014597-66vd2mdu 1007 1 There there EX cord-014597-66vd2mdu 1007 2 was be VBD cord-014597-66vd2mdu 1007 3 minimal minimal JJ cord-014597-66vd2mdu 1007 4 sialylation sialylation NN cord-014597-66vd2mdu 1007 5 in in IN cord-014597-66vd2mdu 1007 6 IL8 IL8 NNP cord-014597-66vd2mdu 1007 7 but but CC cord-014597-66vd2mdu 1007 8 up up IN cord-014597-66vd2mdu 1007 9 to to TO cord-014597-66vd2mdu 1007 10 11 11 CD cord-014597-66vd2mdu 1007 11 % % NN cord-014597-66vd2mdu 1007 12 in in IN cord-014597-66vd2mdu 1007 13 EG2 EG2 NNP cord-014597-66vd2mdu 1007 14 . . . cord-014597-66vd2mdu 1008 1 Glycan glycan JJ cord-014597-66vd2mdu 1008 2 modifications modification NNS cord-014597-66vd2mdu 1008 3 were be VBD cord-014597-66vd2mdu 1008 4 made make VBN cord-014597-66vd2mdu 1008 5 as as IN cord-014597-66vd2mdu 1008 6 each each DT cord-014597-66vd2mdu 1008 7 antibody antibody NN cord-014597-66vd2mdu 1008 8 was be VBD cord-014597-66vd2mdu 1008 9 held hold VBN cord-014597-66vd2mdu 1008 10 on on IN cord-014597-66vd2mdu 1008 11 a a DT cord-014597-66vd2mdu 1008 12 Protein Protein NNP cord-014597-66vd2mdu 1008 13 A a DT cord-014597-66vd2mdu 1008 14 column column NN cord-014597-66vd2mdu 1008 15 in in IN cord-014597-66vd2mdu 1008 16 accordance accordance NN cord-014597-66vd2mdu 1008 17 with with IN cord-014597-66vd2mdu 1008 18 procedures procedure NNS cord-014597-66vd2mdu 1008 19 shown show VBN cord-014597-66vd2mdu 1008 20 in in IN cord-014597-66vd2mdu 1008 21 Table Table NNP cord-014597-66vd2mdu 1008 22 _SP cord-014597-66vd2mdu 1008 23 1 1 CD cord-014597-66vd2mdu 1008 24 . . . cord-014597-66vd2mdu 1009 1 Agalactosylated agalactosylated JJ cord-014597-66vd2mdu 1009 2 glycans glycan NNS cord-014597-66vd2mdu 1009 3 were be VBD cord-014597-66vd2mdu 1009 4 enriched enrich VBN cord-014597-66vd2mdu 1009 5 by by IN cord-014597-66vd2mdu 1009 6 treatment treatment NN cord-014597-66vd2mdu 1009 7 with with IN cord-014597-66vd2mdu 1009 8 the the DT cord-014597-66vd2mdu 1009 9 single single JJ cord-014597-66vd2mdu 1009 10 addition addition NN cord-014597-66vd2mdu 1009 11 of of IN cord-014597-66vd2mdu 1009 12 galactosidase galactosidase NN cord-014597-66vd2mdu 1009 13 and and CC cord-014597-66vd2mdu 1009 14 neuraminidase neuraminidase NN cord-014597-66vd2mdu 1009 15 . . . cord-014597-66vd2mdu 1010 1 This this DT cord-014597-66vd2mdu 1010 2 resulted result VBD cord-014597-66vd2mdu 1010 3 in in IN cord-014597-66vd2mdu 1010 4 83 83 CD cord-014597-66vd2mdu 1010 5 - - SYM cord-014597-66vd2mdu 1010 6 95 95 CD cord-014597-66vd2mdu 1010 7 % % NN cord-014597-66vd2mdu 1010 8 of of IN cord-014597-66vd2mdu 1010 9 agalactosylated agalactosylate VBN cord-014597-66vd2mdu 1010 10 structures structure NNS cord-014597-66vd2mdu 1010 11 in in IN cord-014597-66vd2mdu 1010 12 the the DT cord-014597-66vd2mdu 1010 13 Mabs Mabs NNP cord-014597-66vd2mdu 1010 14 and and CC cord-014597-66vd2mdu 1010 15 65 65 CD cord-014597-66vd2mdu 1010 16 % % NN cord-014597-66vd2mdu 1010 17 in in IN cord-014597-66vd2mdu 1010 18 the the DT cord-014597-66vd2mdu 1010 19 polyclonal polyclonal JJ cord-014597-66vd2mdu 1010 20 antibody antibody NN cord-014597-66vd2mdu 1010 21 . . . cord-014597-66vd2mdu 1011 1 Galactosylated Galactosylated NNP cord-014597-66vd2mdu 1011 2 antibodies antibody NNS cord-014597-66vd2mdu 1011 3 ( ( -LRB- cord-014597-66vd2mdu 1011 4 > > NFP cord-014597-66vd2mdu 1011 5 95 95 CD cord-014597-66vd2mdu 1011 6 % % NN cord-014597-66vd2mdu 1011 7 yield yield NN cord-014597-66vd2mdu 1011 8 ) ) -RRB- cord-014597-66vd2mdu 1011 9 were be VBD cord-014597-66vd2mdu 1011 10 produced produce VBN cord-014597-66vd2mdu 1011 11 by by IN cord-014597-66vd2mdu 1011 12 a a DT cord-014597-66vd2mdu 1011 13 single single JJ cord-014597-66vd2mdu 1011 14 stage stage NN cord-014597-66vd2mdu 1011 15 reaction reaction NN cord-014597-66vd2mdu 1011 16 involving involve VBG cord-014597-66vd2mdu 1011 17 sialidase sialidase NN cord-014597-66vd2mdu 1011 18 and and CC cord-014597-66vd2mdu 1011 19 by by IN cord-014597-66vd2mdu 1011 20 galactosyltransferase galactosyltransferase NNP cord-014597-66vd2mdu 1011 21 with with IN cord-014597-66vd2mdu 1011 22 UDP UDP NNP cord-014597-66vd2mdu 1011 23 - - HYPH cord-014597-66vd2mdu 1011 24 Gal gal NN cord-014597-66vd2mdu 1011 25 . . . cord-014597-66vd2mdu 1012 1 Breakdown breakdown NN cord-014597-66vd2mdu 1012 2 of of IN cord-014597-66vd2mdu 1012 3 the the DT cord-014597-66vd2mdu 1012 4 glycans glycan NNS cord-014597-66vd2mdu 1012 5 to to IN cord-014597-66vd2mdu 1012 6 a a DT cord-014597-66vd2mdu 1012 7 trimannosyl trimannosyl NN cord-014597-66vd2mdu 1012 8 core core NN cord-014597-66vd2mdu 1012 9 was be VBD cord-014597-66vd2mdu 1012 10 accomplished accomplish VBN cord-014597-66vd2mdu 1012 11 by by IN cord-014597-66vd2mdu 1012 12 treatment treatment NN cord-014597-66vd2mdu 1012 13 of of IN cord-014597-66vd2mdu 1012 14 the the DT cord-014597-66vd2mdu 1012 15 agalactosylated agalactosylate VBN cord-014597-66vd2mdu 1012 16 structures structure NNS cord-014597-66vd2mdu 1012 17 with with IN cord-014597-66vd2mdu 1012 18 hexosaminidase hexosaminidase NNP cord-014597-66vd2mdu 1012 19 . . . cord-014597-66vd2mdu 1013 1 This this DT cord-014597-66vd2mdu 1013 2 produced produce VBD cord-014597-66vd2mdu 1013 3 a a DT cord-014597-66vd2mdu 1013 4 yield yield NN cord-014597-66vd2mdu 1013 5 of of IN cord-014597-66vd2mdu 1013 6 76 76 CD cord-014597-66vd2mdu 1013 7 - - SYM cord-014597-66vd2mdu 1013 8 80 80 CD cord-014597-66vd2mdu 1013 9 % % NN cord-014597-66vd2mdu 1013 10 of of IN cord-014597-66vd2mdu 1013 11 the the DT cord-014597-66vd2mdu 1013 12 FM3 FM3 NNP cord-014597-66vd2mdu 1013 13 structure structure NN cord-014597-66vd2mdu 1013 14 with with IN cord-014597-66vd2mdu 1013 15 a a DT cord-014597-66vd2mdu 1013 16 small small JJ cord-014597-66vd2mdu 1013 17 remainder remainder NN cord-014597-66vd2mdu 1013 18 of of IN cord-014597-66vd2mdu 1013 19 FA1 FA1 NNP cord-014597-66vd2mdu 1013 20 . . . cord-014597-66vd2mdu 1014 1 Sialylated sialylated JJ cord-014597-66vd2mdu 1014 2 antibodies antibody NNS cord-014597-66vd2mdu 1014 3 ( ( -LRB- cord-014597-66vd2mdu 1014 4 > > NFP cord-014597-66vd2mdu 1014 5 95 95 CD cord-014597-66vd2mdu 1014 6 % % NN cord-014597-66vd2mdu 1014 7 ) ) -RRB- cord-014597-66vd2mdu 1014 8 were be VBD cord-014597-66vd2mdu 1014 9 produced produce VBN cord-014597-66vd2mdu 1014 10 by by IN cord-014597-66vd2mdu 1014 11 a a DT cord-014597-66vd2mdu 1014 12 2 2 CD cord-014597-66vd2mdu 1014 13 stage stage NN cord-014597-66vd2mdu 1014 14 reaction reaction NN cord-014597-66vd2mdu 1014 15 involving involve VBG cord-014597-66vd2mdu 1014 16 sialidase sialidase NN cord-014597-66vd2mdu 1014 17 , , , cord-014597-66vd2mdu 1014 18 galactosyltransferase galactosyltransferase NNP cord-014597-66vd2mdu 1014 19 and and CC cord-014597-66vd2mdu 1014 20 finally finally RB cord-014597-66vd2mdu 1014 21 treatment treatment NN cord-014597-66vd2mdu 1014 22 with with IN cord-014597-66vd2mdu 1014 23 2,6 2,6 CD cord-014597-66vd2mdu 1014 24 sialyltransferase sialyltransferase NN cord-014597-66vd2mdu 1014 25 in in IN cord-014597-66vd2mdu 1014 26 the the DT cord-014597-66vd2mdu 1014 27 presence presence NN cord-014597-66vd2mdu 1014 28 of of IN cord-014597-66vd2mdu 1014 29 CMP CMP NNP cord-014597-66vd2mdu 1014 30 - - HYPH cord-014597-66vd2mdu 1014 31 NANA NANA NNP cord-014597-66vd2mdu 1014 32 . . . cord-014597-66vd2mdu 1015 1 The the DT cord-014597-66vd2mdu 1015 2 latter latter JJ cord-014597-66vd2mdu 1015 3 reaction reaction NN cord-014597-66vd2mdu 1015 4 produced produce VBD cord-014597-66vd2mdu 1015 5 equimolar equimolar JJ cord-014597-66vd2mdu 1015 6 quantities quantity NNS cord-014597-66vd2mdu 1015 7 of of IN cord-014597-66vd2mdu 1015 8 monosialylated monosialylate VBN cord-014597-66vd2mdu 1015 9 and and CC cord-014597-66vd2mdu 1015 10 disialylated disialylate VBN cord-014597-66vd2mdu 1015 11 Cetuximab Cetuximab NNP cord-014597-66vd2mdu 1015 12 and and CC cord-014597-66vd2mdu 1015 13 polyclonal polyclonal JJ cord-014597-66vd2mdu 1015 14 antibodies antibody NNS cord-014597-66vd2mdu 1015 15 . . . cord-014597-66vd2mdu 1016 1 The the DT cord-014597-66vd2mdu 1016 2 results result NNS cord-014597-66vd2mdu 1016 3 suggest suggest VBP cord-014597-66vd2mdu 1016 4 that that IN cord-014597-66vd2mdu 1016 5 for for IN cord-014597-66vd2mdu 1016 6 human human JJ cord-014597-66vd2mdu 1016 7 antibodies antibody NNS cord-014597-66vd2mdu 1016 8 ( ( -LRB- cord-014597-66vd2mdu 1016 9 150 150 CD cord-014597-66vd2mdu 1016 10 kDa kDa NNPS cord-014597-66vd2mdu 1016 11 ) ) -RRB- cord-014597-66vd2mdu 1016 12 there there EX cord-014597-66vd2mdu 1016 13 may may MD cord-014597-66vd2mdu 1016 14 be be VB cord-014597-66vd2mdu 1016 15 a a DT cord-014597-66vd2mdu 1016 16 limitation limitation NN cord-014597-66vd2mdu 1016 17 for for IN cord-014597-66vd2mdu 1016 18 sialylation sialylation NN cord-014597-66vd2mdu 1016 19 given give VBN cord-014597-66vd2mdu 1016 20 the the DT cord-014597-66vd2mdu 1016 21 steric steric JJ cord-014597-66vd2mdu 1016 22 constraints constraint NNS cord-014597-66vd2mdu 1016 23 between between IN cord-014597-66vd2mdu 1016 24 the the DT cord-014597-66vd2mdu 1016 25 two two CD cord-014597-66vd2mdu 1016 26 CH2 CH2 NNP cord-014597-66vd2mdu 1016 27 domains domain NNS cord-014597-66vd2mdu 1016 28 of of IN cord-014597-66vd2mdu 1016 29 the the DT cord-014597-66vd2mdu 1016 30 dimeric dimeric JJ cord-014597-66vd2mdu 1016 31 structure structure NN cord-014597-66vd2mdu 1016 32 . . . cord-014597-66vd2mdu 1017 1 The the DT cord-014597-66vd2mdu 1017 2 ability ability NN cord-014597-66vd2mdu 1017 3 to to TO cord-014597-66vd2mdu 1017 4 sialylate sialylate VB cord-014597-66vd2mdu 1017 5 the the DT cord-014597-66vd2mdu 1017 6 smaller small JJR cord-014597-66vd2mdu 1017 7 camelid camelid NNP cord-014597-66vd2mdu 1017 8 antibody antibody NN cord-014597-66vd2mdu 1017 9 ( ( -LRB- cord-014597-66vd2mdu 1017 10 80 80 CD cord-014597-66vd2mdu 1017 11 kDa kDa NNS cord-014597-66vd2mdu 1017 12 ) ) -RRB- cord-014597-66vd2mdu 1017 13 was be VBD cord-014597-66vd2mdu 1017 14 greater great JJR cord-014597-66vd2mdu 1017 15 resulting result VBG cord-014597-66vd2mdu 1017 16 in in IN cord-014597-66vd2mdu 1017 17 a a DT cord-014597-66vd2mdu 1017 18 high high JJ cord-014597-66vd2mdu 1017 19 ( ( -LRB- cord-014597-66vd2mdu 1017 20 > > NFP cord-014597-66vd2mdu 1017 21 90 90 CD cord-014597-66vd2mdu 1017 22 % % NN cord-014597-66vd2mdu 1017 23 ) ) -RRB- cord-014597-66vd2mdu 1017 24 level level NN cord-014597-66vd2mdu 1017 25 of of IN cord-014597-66vd2mdu 1017 26 disialylated disialylated JJ cord-014597-66vd2mdu 1017 27 glycans glycan NNS cord-014597-66vd2mdu 1017 28 . . . cord-014597-66vd2mdu 1018 1 This this DT cord-014597-66vd2mdu 1018 2 suggests suggest VBZ cord-014597-66vd2mdu 1018 3 that that IN cord-014597-66vd2mdu 1018 4 the the DT cord-014597-66vd2mdu 1018 5 steric steric JJ cord-014597-66vd2mdu 1018 6 constraints constraint NNS cord-014597-66vd2mdu 1018 7 for for IN cord-014597-66vd2mdu 1018 8 glycosylation glycosylation NN cord-014597-66vd2mdu 1018 9 may may MD cord-014597-66vd2mdu 1018 10 be be VB cord-014597-66vd2mdu 1018 11 lower low JJR cord-014597-66vd2mdu 1018 12 . . . cord-014597-66vd2mdu 1019 1 These these DT cord-014597-66vd2mdu 1019 2 sialylated sialylate VBN cord-014597-66vd2mdu 1019 3 antibodies antibody NNS cord-014597-66vd2mdu 1019 4 have have VBP cord-014597-66vd2mdu 1019 5 significant significant JJ cord-014597-66vd2mdu 1019 6 potential potential JJ cord-014597-66vd2mdu 1019 7 clinical clinical JJ cord-014597-66vd2mdu 1019 8 importance importance NN cord-014597-66vd2mdu 1019 9 for for IN cord-014597-66vd2mdu 1019 10 their -PRON- PRP$ cord-014597-66vd2mdu 1019 11 ant ant JJ cord-014597-66vd2mdu 1019 12 - - HYPH cord-014597-66vd2mdu 1019 13 inflammatory inflammatory JJ cord-014597-66vd2mdu 1019 14 activities activity NNS cord-014597-66vd2mdu 1019 15 . . . cord-014597-66vd2mdu 1020 1 We -PRON- PRP cord-014597-66vd2mdu 1020 2 have have VBP cord-014597-66vd2mdu 1020 3 modified modify VBN cord-014597-66vd2mdu 1020 4 the the DT cord-014597-66vd2mdu 1020 5 glycans glycan NNS cord-014597-66vd2mdu 1020 6 of of IN cord-014597-66vd2mdu 1020 7 antibodies antibody NNS cord-014597-66vd2mdu 1020 8 following follow VBG cord-014597-66vd2mdu 1020 9 immobilization immobilization NN cord-014597-66vd2mdu 1020 10 on on IN cord-014597-66vd2mdu 1020 11 an an DT cord-014597-66vd2mdu 1020 12 affinity affinity NN cord-014597-66vd2mdu 1020 13 ligand ligand NN cord-014597-66vd2mdu 1020 14 column column NN cord-014597-66vd2mdu 1020 15 . . . cord-014597-66vd2mdu 1021 1 This this DT cord-014597-66vd2mdu 1021 2 allows allow VBZ cord-014597-66vd2mdu 1021 3 enzymatic enzymatic JJ cord-014597-66vd2mdu 1021 4 transformation transformation NN cord-014597-66vd2mdu 1021 5 in in IN cord-014597-66vd2mdu 1021 6 a a DT cord-014597-66vd2mdu 1021 7 solid solid JJ cord-014597-66vd2mdu 1021 8 state state NN cord-014597-66vd2mdu 1021 9 that that WDT cord-014597-66vd2mdu 1021 10 has have VBZ cord-014597-66vd2mdu 1021 11 a a DT cord-014597-66vd2mdu 1021 12 distinct distinct JJ cord-014597-66vd2mdu 1021 13 advantage advantage NN cord-014597-66vd2mdu 1021 14 over over IN cord-014597-66vd2mdu 1021 15 the the DT cord-014597-66vd2mdu 1021 16 equivalent equivalent JJ cord-014597-66vd2mdu 1021 17 transformation transformation NN cord-014597-66vd2mdu 1021 18 in in IN cord-014597-66vd2mdu 1021 19 solution solution NN cord-014597-66vd2mdu 1021 20 because because IN cord-014597-66vd2mdu 1021 21 the the DT cord-014597-66vd2mdu 1021 22 enzymes enzyme NNS cord-014597-66vd2mdu 1021 23 and and CC cord-014597-66vd2mdu 1021 24 buffers buffer NNS cord-014597-66vd2mdu 1021 25 can can MD cord-014597-66vd2mdu 1021 26 be be VB cord-014597-66vd2mdu 1021 27 washed wash VBN cord-014597-66vd2mdu 1021 28 out out RP cord-014597-66vd2mdu 1021 29 on on IN cord-014597-66vd2mdu 1021 30 completion completion NN cord-014597-66vd2mdu 1021 31 of of IN cord-014597-66vd2mdu 1021 32 the the DT cord-014597-66vd2mdu 1021 33 modification modification NN cord-014597-66vd2mdu 1021 34 leaving leave VBG cord-014597-66vd2mdu 1021 35 the the DT cord-014597-66vd2mdu 1021 36 antibody antibody NN cord-014597-66vd2mdu 1021 37 still still RB cord-014597-66vd2mdu 1021 38 attached attach VBN cord-014597-66vd2mdu 1021 39 to to IN cord-014597-66vd2mdu 1021 40 the the DT cord-014597-66vd2mdu 1021 41 affinity affinity NN cord-014597-66vd2mdu 1021 42 ligand ligand NN cord-014597-66vd2mdu 1021 43 . . . cord-014597-66vd2mdu 1022 1 This this DT cord-014597-66vd2mdu 1022 2 enables enable VBZ cord-014597-66vd2mdu 1022 3 repeated repeat VBD cord-014597-66vd2mdu 1022 4 rounds round NNS cord-014597-66vd2mdu 1022 5 of of IN cord-014597-66vd2mdu 1022 6 an an DT cord-014597-66vd2mdu 1022 7 enzymatic enzymatic JJ cord-014597-66vd2mdu 1022 8 reaction reaction NN cord-014597-66vd2mdu 1022 9 or or CC cord-014597-66vd2mdu 1022 10 sequential sequential JJ cord-014597-66vd2mdu 1022 11 reaction reaction NN cord-014597-66vd2mdu 1022 12 steps step NNS cord-014597-66vd2mdu 1022 13 without without IN cord-014597-66vd2mdu 1022 14 the the DT cord-014597-66vd2mdu 1022 15 need need NN cord-014597-66vd2mdu 1022 16 for for IN cord-014597-66vd2mdu 1022 17 intermediate intermediate JJ cord-014597-66vd2mdu 1022 18 antibody antibody NN cord-014597-66vd2mdu 1022 19 purification purification NN cord-014597-66vd2mdu 1022 20 . . . cord-014597-66vd2mdu 1023 1 The the DT cord-014597-66vd2mdu 1023 2 antibody antibody NN cord-014597-66vd2mdu 1023 3 can can MD cord-014597-66vd2mdu 1023 4 be be VB cord-014597-66vd2mdu 1023 5 removed remove VBN cord-014597-66vd2mdu 1023 6 eventually eventually RB cord-014597-66vd2mdu 1023 7 from from IN cord-014597-66vd2mdu 1023 8 the the DT cord-014597-66vd2mdu 1023 9 column column NN cord-014597-66vd2mdu 1023 10 by by IN cord-014597-66vd2mdu 1023 11 application application NN cord-014597-66vd2mdu 1023 12 of of IN cord-014597-66vd2mdu 1023 13 an an DT cord-014597-66vd2mdu 1023 14 elution elution NN cord-014597-66vd2mdu 1023 15 buffer buffer NN cord-014597-66vd2mdu 1023 16 once once RB cord-014597-66vd2mdu 1023 17 all all DT cord-014597-66vd2mdu 1023 18 desired desire VBN cord-014597-66vd2mdu 1023 19 glycan glycan NN cord-014597-66vd2mdu 1023 20 modification modification NN cord-014597-66vd2mdu 1023 21 have have VBP cord-014597-66vd2mdu 1023 22 been be VBN cord-014597-66vd2mdu 1023 23 made make VBN cord-014597-66vd2mdu 1023 24 . . . cord-014597-66vd2mdu 1024 1 Since since IN cord-014597-66vd2mdu 1024 2 affinity affinity NN cord-014597-66vd2mdu 1024 3 ligand ligand NN cord-014597-66vd2mdu 1024 4 purification purification NN cord-014597-66vd2mdu 1024 5 of of IN cord-014597-66vd2mdu 1024 6 antibodies antibody NNS cord-014597-66vd2mdu 1024 7 is be VBZ cord-014597-66vd2mdu 1024 8 performed perform VBN cord-014597-66vd2mdu 1024 9 routinely routinely RB cord-014597-66vd2mdu 1024 10 as as IN cord-014597-66vd2mdu 1024 11 an an DT cord-014597-66vd2mdu 1024 12 initial initial JJ cord-014597-66vd2mdu 1024 13 step step NN cord-014597-66vd2mdu 1024 14 of of IN cord-014597-66vd2mdu 1024 15 purification purification NN cord-014597-66vd2mdu 1024 16 after after IN cord-014597-66vd2mdu 1024 17 cell cell NN cord-014597-66vd2mdu 1024 18 culture culture NN cord-014597-66vd2mdu 1024 19 , , , cord-014597-66vd2mdu 1024 20 the the DT cord-014597-66vd2mdu 1024 21 glycan glycan NN cord-014597-66vd2mdu 1024 22 modification modification NN cord-014597-66vd2mdu 1024 23 can can MD cord-014597-66vd2mdu 1024 24 easily easily RB cord-014597-66vd2mdu 1024 25 be be VB cord-014597-66vd2mdu 1024 26 incorporated incorporate VBN cord-014597-66vd2mdu 1024 27 into into IN cord-014597-66vd2mdu 1024 28 this this DT cord-014597-66vd2mdu 1024 29 process process NN cord-014597-66vd2mdu 1024 30 . . . cord-014597-66vd2mdu 1025 1 The the DT cord-014597-66vd2mdu 1025 2 enrichment enrichment NN cord-014597-66vd2mdu 1025 3 of of IN cord-014597-66vd2mdu 1025 4 the the DT cord-014597-66vd2mdu 1025 5 resulting result VBG cord-014597-66vd2mdu 1025 6 antibody antibody NN cord-014597-66vd2mdu 1025 7 for for IN cord-014597-66vd2mdu 1025 8 a a DT cord-014597-66vd2mdu 1025 9 targeted target VBN cord-014597-66vd2mdu 1025 10 glycoform glycoform NN cord-014597-66vd2mdu 1025 11 can can MD cord-014597-66vd2mdu 1025 12 enhance enhance VB cord-014597-66vd2mdu 1025 13 the the DT cord-014597-66vd2mdu 1025 14 potential potential JJ cord-014597-66vd2mdu 1025 15 therapeutic therapeutic JJ cord-014597-66vd2mdu 1025 16 efficacy efficacy NN cord-014597-66vd2mdu 1025 17 as as IN cord-014597-66vd2mdu 1025 18 it -PRON- PRP cord-014597-66vd2mdu 1025 19 is be VBZ cord-014597-66vd2mdu 1025 20 known know VBN cord-014597-66vd2mdu 1025 21 that that IN cord-014597-66vd2mdu 1025 22 specific specific JJ cord-014597-66vd2mdu 1025 23 glycoforms glycoform NNS cord-014597-66vd2mdu 1025 24 are be VBP cord-014597-66vd2mdu 1025 25 required require VBN cord-014597-66vd2mdu 1025 26 for for IN cord-014597-66vd2mdu 1025 27 certain certain JJ cord-014597-66vd2mdu 1025 28 biological biological JJ cord-014597-66vd2mdu 1025 29 effects effect NNS cord-014597-66vd2mdu 1025 30 . . . cord-014597-66vd2mdu 1026 1 [ [ -LRB- cord-014597-66vd2mdu 1026 2 1 1 CD cord-014597-66vd2mdu 1026 3 , , , cord-014597-66vd2mdu 1026 4 2 2 CD cord-014597-66vd2mdu 1026 5 ] ] -RRB- cord-014597-66vd2mdu 1026 6 . . . cord-014597-66vd2mdu 1027 1 This this DT cord-014597-66vd2mdu 1027 2 is be VBZ cord-014597-66vd2mdu 1027 3 mainly mainly RB cord-014597-66vd2mdu 1027 4 because because IN cord-014597-66vd2mdu 1027 5 microvesicles microvesicle NNS cord-014597-66vd2mdu 1027 6 can can MD cord-014597-66vd2mdu 1027 7 be be VB cord-014597-66vd2mdu 1027 8 enriched enrich VBN cord-014597-66vd2mdu 1027 9 / / SYM cord-014597-66vd2mdu 1027 10 deprived deprive VBN cord-014597-66vd2mdu 1027 11 for for IN cord-014597-66vd2mdu 1027 12 specific specific JJ cord-014597-66vd2mdu 1027 13 proteins protein NNS cord-014597-66vd2mdu 1027 14 , , , cord-014597-66vd2mdu 1027 15 based base VBN cord-014597-66vd2mdu 1027 16 on on IN cord-014597-66vd2mdu 1027 17 their -PRON- PRP$ cord-014597-66vd2mdu 1027 18 functional functional JJ cord-014597-66vd2mdu 1027 19 purpose purpose NN cord-014597-66vd2mdu 1027 20 and and CC cord-014597-66vd2mdu 1027 21 their -PRON- PRP$ cord-014597-66vd2mdu 1027 22 cellular cellular JJ cord-014597-66vd2mdu 1027 23 origin origin NN cord-014597-66vd2mdu 1027 24 . . . cord-014597-66vd2mdu 1028 1 Recently recently RB cord-014597-66vd2mdu 1028 2 , , , cord-014597-66vd2mdu 1028 3 microvesicles microvesicle NNS cord-014597-66vd2mdu 1028 4 purified purify VBN cord-014597-66vd2mdu 1028 5 from from IN cord-014597-66vd2mdu 1028 6 the the DT cord-014597-66vd2mdu 1028 7 supernatant supernatant NN cord-014597-66vd2mdu 1028 8 of of IN cord-014597-66vd2mdu 1028 9 T24 T24 NNP cord-014597-66vd2mdu 1028 10 bladder bladder NN cord-014597-66vd2mdu 1028 11 cancer cancer NN cord-014597-66vd2mdu 1028 12 cells cell NNS cord-014597-66vd2mdu 1028 13 were be VBD cord-014597-66vd2mdu 1028 14 reported report VBN cord-014597-66vd2mdu 1028 15 to to TO cord-014597-66vd2mdu 1028 16 be be VB cord-014597-66vd2mdu 1028 17 enriched enrich VBN cord-014597-66vd2mdu 1028 18 for for IN cord-014597-66vd2mdu 1028 19 Bcl-2 Bcl-2 NNP cord-014597-66vd2mdu 1028 20 and and CC cord-014597-66vd2mdu 1028 21 cyclin cyclin NN cord-014597-66vd2mdu 1028 22 D1 d1 NN cord-014597-66vd2mdu 1028 23 ( ( -LRB- cord-014597-66vd2mdu 1028 24 anti anti JJ cord-014597-66vd2mdu 1028 25 - - JJ cord-014597-66vd2mdu 1028 26 apoptotic apoptotic JJ cord-014597-66vd2mdu 1028 27 proteins protein NNS cord-014597-66vd2mdu 1028 28 ) ) -RRB- cord-014597-66vd2mdu 1028 29 , , , cord-014597-66vd2mdu 1028 30 but but CC cord-014597-66vd2mdu 1028 31 deprived deprive VBN cord-014597-66vd2mdu 1028 32 for for IN cord-014597-66vd2mdu 1028 33 Bax Bax NNP cord-014597-66vd2mdu 1028 34 and and CC cord-014597-66vd2mdu 1028 35 caspase-3 caspase-3 NNP cord-014597-66vd2mdu 1028 36 proteins protein NNS cord-014597-66vd2mdu 1028 37 ( ( -LRB- cord-014597-66vd2mdu 1028 38 pro pro JJ cord-014597-66vd2mdu 1028 39 - - JJ cord-014597-66vd2mdu 1028 40 apoptotic apoptotic JJ cord-014597-66vd2mdu 1028 41 proteins protein NNS cord-014597-66vd2mdu 1028 42 ) ) -RRB- cord-014597-66vd2mdu 1028 43 contributing contribute VBG cord-014597-66vd2mdu 1028 44 towards towards IN cord-014597-66vd2mdu 1028 45 immunity immunity NN cord-014597-66vd2mdu 1028 46 against against IN cord-014597-66vd2mdu 1028 47 programmed program VBN cord-014597-66vd2mdu 1028 48 cell cell NN cord-014597-66vd2mdu 1028 49 - - HYPH cord-014597-66vd2mdu 1028 50 death death NN cord-014597-66vd2mdu 1028 51 [ [ -LRB- cord-014597-66vd2mdu 1028 52 2 2 CD cord-014597-66vd2mdu 1028 53 ] ] -RRB- cord-014597-66vd2mdu 1028 54 . . . cord-014597-66vd2mdu 1029 1 However however RB cord-014597-66vd2mdu 1029 2 , , , cord-014597-66vd2mdu 1029 3 impact impact NN cord-014597-66vd2mdu 1029 4 of of IN cord-014597-66vd2mdu 1029 5 microvesicles microvesicle NNS cord-014597-66vd2mdu 1029 6 on on IN cord-014597-66vd2mdu 1029 7 CHO CHO NNP cord-014597-66vd2mdu 1029 8 - - HYPH cord-014597-66vd2mdu 1029 9 based base VBN cord-014597-66vd2mdu 1029 10 bioprocess bioprocess NN cord-014597-66vd2mdu 1029 11 has have VBZ cord-014597-66vd2mdu 1029 12 not not RB cord-014597-66vd2mdu 1029 13 been be VBN cord-014597-66vd2mdu 1029 14 evaluated evaluate VBN cord-014597-66vd2mdu 1029 15 yet yet RB cord-014597-66vd2mdu 1029 16 . . . cord-014597-66vd2mdu 1030 1 Therefore therefore RB cord-014597-66vd2mdu 1030 2 , , , cord-014597-66vd2mdu 1030 3 in in IN cord-014597-66vd2mdu 1030 4 this this DT cord-014597-66vd2mdu 1030 5 investigation investigation NN cord-014597-66vd2mdu 1030 6 , , , cord-014597-66vd2mdu 1030 7 we -PRON- PRP cord-014597-66vd2mdu 1030 8 aimed aim VBD cord-014597-66vd2mdu 1030 9 to to TO cord-014597-66vd2mdu 1030 10 evaluate evaluate VB cord-014597-66vd2mdu 1030 11 their -PRON- PRP$ cord-014597-66vd2mdu 1030 12 impact impact NN cord-014597-66vd2mdu 1030 13 on on IN cord-014597-66vd2mdu 1030 14 cell cell NN cord-014597-66vd2mdu 1030 15 growth growth NN cord-014597-66vd2mdu 1030 16 and and CC cord-014597-66vd2mdu 1030 17 recombinant recombinant JJ cord-014597-66vd2mdu 1030 18 protein protein NN cord-014597-66vd2mdu 1030 19 production production NN cord-014597-66vd2mdu 1030 20 from from IN cord-014597-66vd2mdu 1030 21 CHO CHO NNP cord-014597-66vd2mdu 1030 22 cells cell NNS cord-014597-66vd2mdu 1030 23 . . . cord-014597-66vd2mdu 1031 1 Materials material NNS cord-014597-66vd2mdu 1031 2 and and CC cord-014597-66vd2mdu 1031 3 methods method NNS cord-014597-66vd2mdu 1031 4 CHO CHO NNP cord-014597-66vd2mdu 1031 5 - - HYPH cord-014597-66vd2mdu 1031 6 K1 K1 NNP cord-014597-66vd2mdu 1031 7 cells cell NNS cord-014597-66vd2mdu 1031 8 were be VBD cord-014597-66vd2mdu 1031 9 grown grow VBN cord-014597-66vd2mdu 1031 10 in in IN cord-014597-66vd2mdu 1031 11 chemically chemically RB cord-014597-66vd2mdu 1031 12 - - HYPH cord-014597-66vd2mdu 1031 13 defined define VBN cord-014597-66vd2mdu 1031 14 protein protein NN cord-014597-66vd2mdu 1031 15 - - HYPH cord-014597-66vd2mdu 1031 16 free free JJ cord-014597-66vd2mdu 1031 17 culture culture NN cord-014597-66vd2mdu 1031 18 medium medium NN cord-014597-66vd2mdu 1031 19 ( ( -LRB- cord-014597-66vd2mdu 1031 20 Life Life NNP cord-014597-66vd2mdu 1031 21 Technologies-1835273 Technologies-1835273 NNP cord-014597-66vd2mdu 1031 22 ) ) -RRB- cord-014597-66vd2mdu 1031 23 in in IN cord-014597-66vd2mdu 1031 24 shake shake NN cord-014597-66vd2mdu 1031 25 flask flask NN cord-014597-66vd2mdu 1031 26 ( ( -LRB- cord-014597-66vd2mdu 1031 27 GX-00125P GX-00125P NNP cord-014597-66vd2mdu 1031 28 ) ) -RRB- cord-014597-66vd2mdu 1031 29 . . . cord-014597-66vd2mdu 1032 1 The the DT cord-014597-66vd2mdu 1032 2 different different JJ cord-014597-66vd2mdu 1032 3 fractions fraction NNS cord-014597-66vd2mdu 1032 4 of of IN cord-014597-66vd2mdu 1032 5 spent spend VBN cord-014597-66vd2mdu 1032 6 - - HYPH cord-014597-66vd2mdu 1032 7 media medium NNS cord-014597-66vd2mdu 1032 8 ( ( -LRB- cord-014597-66vd2mdu 1032 9 microvesicles microvesicles NNP cord-014597-66vd2mdu 1032 10 and and CC cord-014597-66vd2mdu 1032 11 microvesicle microvesicle NNP cord-014597-66vd2mdu 1032 12 - - HYPH cord-014597-66vd2mdu 1032 13 free free JJ cord-014597-66vd2mdu 1032 14 spent spend VBN cord-014597-66vd2mdu 1032 15 media medium NNS cord-014597-66vd2mdu 1032 16 ) ) -RRB- cord-014597-66vd2mdu 1032 17 were be VBD cord-014597-66vd2mdu 1032 18 collected collect VBN cord-014597-66vd2mdu 1032 19 using use VBG cord-014597-66vd2mdu 1032 20 ultracentrifugation ultracentrifugation NN cord-014597-66vd2mdu 1032 21 method method NN cord-014597-66vd2mdu 1032 22 [ [ -LRB- cord-014597-66vd2mdu 1032 23 1 1 CD cord-014597-66vd2mdu 1032 24 , , , cord-014597-66vd2mdu 1032 25 3 3 CD cord-014597-66vd2mdu 1032 26 ] ] -RRB- cord-014597-66vd2mdu 1032 27 . . . cord-014597-66vd2mdu 1033 1 Quality quality NN cord-014597-66vd2mdu 1033 2 of of IN cord-014597-66vd2mdu 1033 3 different different JJ cord-014597-66vd2mdu 1033 4 fractions fraction NNS cord-014597-66vd2mdu 1033 5 was be VBD cord-014597-66vd2mdu 1033 6 ensured ensure VBN cord-014597-66vd2mdu 1033 7 using use VBG cord-014597-66vd2mdu 1033 8 Western western JJ cord-014597-66vd2mdu 1033 9 blotting blotting NN cord-014597-66vd2mdu 1033 10 for for IN cord-014597-66vd2mdu 1033 11 exosomal exosomal JJ cord-014597-66vd2mdu 1033 12 marker marker NN cord-014597-66vd2mdu 1033 13 , , , cord-014597-66vd2mdu 1033 14 CD63 CD63 NNP cord-014597-66vd2mdu 1033 15 ( ( -LRB- cord-014597-66vd2mdu 1033 16 SC-15363 SC-15363 NNP cord-014597-66vd2mdu 1033 17 ) ) -RRB- cord-014597-66vd2mdu 1033 18 and and CC cord-014597-66vd2mdu 1033 19 coomassie coomassie VB cord-014597-66vd2mdu 1033 20 stained stain VBN cord-014597-66vd2mdu 1033 21 gel gel NN cord-014597-66vd2mdu 1033 22 for for IN cord-014597-66vd2mdu 1033 23 loading loading NN cord-014597-66vd2mdu 1033 24 control control NN cord-014597-66vd2mdu 1033 25 ( ( -LRB- cord-014597-66vd2mdu 1033 26 Fig Fig NNP cord-014597-66vd2mdu 1033 27 . . . cord-014597-66vd2mdu 1033 28 1a 1a CD cord-014597-66vd2mdu 1033 29 ) ) -RRB- cord-014597-66vd2mdu 1033 30 . . . cord-014597-66vd2mdu 1034 1 To to TO cord-014597-66vd2mdu 1034 2 evaluate evaluate VB cord-014597-66vd2mdu 1034 3 impact impact NN cord-014597-66vd2mdu 1034 4 on on IN cord-014597-66vd2mdu 1034 5 cell cell NN cord-014597-66vd2mdu 1034 6 growth growth NN cord-014597-66vd2mdu 1034 7 , , , cord-014597-66vd2mdu 1034 8 cells cell NNS cord-014597-66vd2mdu 1034 9 were be VBD cord-014597-66vd2mdu 1034 10 seeded seed VBN cord-014597-66vd2mdu 1034 11 with with IN cord-014597-66vd2mdu 1034 12 microvesicles microvesicle NNS cord-014597-66vd2mdu 1034 13 and and CC cord-014597-66vd2mdu 1034 14 microvesicle microvesicle NNP cord-014597-66vd2mdu 1034 15 - - HYPH cord-014597-66vd2mdu 1034 16 free free JJ cord-014597-66vd2mdu 1034 17 fraction fraction NN cord-014597-66vd2mdu 1034 18 collected collect VBN cord-014597-66vd2mdu 1034 19 from from IN cord-014597-66vd2mdu 1034 20 log log NN cord-014597-66vd2mdu 1034 21 - - HYPH cord-014597-66vd2mdu 1034 22 phase phase NN cord-014597-66vd2mdu 1034 23 of of IN cord-014597-66vd2mdu 1034 24 culture culture NN cord-014597-66vd2mdu 1034 25 and and CC cord-014597-66vd2mdu 1034 26 cell cell NN cord-014597-66vd2mdu 1034 27 counts count NNS cord-014597-66vd2mdu 1034 28 were be VBD cord-014597-66vd2mdu 1034 29 performed perform VBN cord-014597-66vd2mdu 1034 30 by by IN cord-014597-66vd2mdu 1034 31 ViCell vicell NN cord-014597-66vd2mdu 1034 32 using use VBG cord-014597-66vd2mdu 1034 33 trypan trypan NNP cord-014597-66vd2mdu 1034 34 - - HYPH cord-014597-66vd2mdu 1034 35 blue blue JJ cord-014597-66vd2mdu 1034 36 dye dye NN cord-014597-66vd2mdu 1034 37 exclusion exclusion NN cord-014597-66vd2mdu 1034 38 method method NN cord-014597-66vd2mdu 1034 39 . . . cord-014597-66vd2mdu 1035 1 For for IN cord-014597-66vd2mdu 1035 2 impact impact NN cord-014597-66vd2mdu 1035 3 on on IN cord-014597-66vd2mdu 1035 4 productivity productivity NN cord-014597-66vd2mdu 1035 5 , , , cord-014597-66vd2mdu 1035 6 cell cell NN cord-014597-66vd2mdu 1035 7 - - HYPH cord-014597-66vd2mdu 1035 8 free free JJ cord-014597-66vd2mdu 1035 9 supernatant supernatant NN cord-014597-66vd2mdu 1035 10 , , , cord-014597-66vd2mdu 1035 11 collected collect VBN cord-014597-66vd2mdu 1035 12 from from IN cord-014597-66vd2mdu 1035 13 microvesicle microvesicle NNP cord-014597-66vd2mdu 1035 14 - - HYPH cord-014597-66vd2mdu 1035 15 treated treat VBN cord-014597-66vd2mdu 1035 16 human human JJ cord-014597-66vd2mdu 1035 17 IgG igg NN cord-014597-66vd2mdu 1035 18 secreting secrete VBG cord-014597-66vd2mdu 1035 19 CHO CHO NNP cord-014597-66vd2mdu 1035 20 culture culture NN cord-014597-66vd2mdu 1035 21 from from IN cord-014597-66vd2mdu 1035 22 stationary stationary JJ cord-014597-66vd2mdu 1035 23 - - HYPH cord-014597-66vd2mdu 1035 24 phase phase NN cord-014597-66vd2mdu 1035 25 of of IN cord-014597-66vd2mdu 1035 26 culture culture NN cord-014597-66vd2mdu 1035 27 with with IN cord-014597-66vd2mdu 1035 28 respective respective JJ cord-014597-66vd2mdu 1035 29 control control NN cord-014597-66vd2mdu 1035 30 , , , cord-014597-66vd2mdu 1035 31 was be VBD cord-014597-66vd2mdu 1035 32 evaluated evaluate VBN cord-014597-66vd2mdu 1035 33 using use VBG cord-014597-66vd2mdu 1035 34 ELISA ELISA NNP cord-014597-66vd2mdu 1035 35 ( ( -LRB- cord-014597-66vd2mdu 1035 36 ab100547 ab100547 NNP cord-014597-66vd2mdu 1035 37 ) ) -RRB- cord-014597-66vd2mdu 1035 38 . . . cord-014597-66vd2mdu 1036 1 Microvesicles microvesicle NNS cord-014597-66vd2mdu 1036 2 collected collect VBN cord-014597-66vd2mdu 1036 3 from from IN cord-014597-66vd2mdu 1036 4 10 10 CD cord-014597-66vd2mdu 1036 5 % % NN cord-014597-66vd2mdu 1036 6 of of IN cord-014597-66vd2mdu 1036 7 media medium NNS cord-014597-66vd2mdu 1036 8 ( ( -LRB- cord-014597-66vd2mdu 1036 9 by by IN cord-014597-66vd2mdu 1036 10 volume volume NN cord-014597-66vd2mdu 1036 11 ) ) -RRB- cord-014597-66vd2mdu 1036 12 from from IN cord-014597-66vd2mdu 1036 13 routine routine JJ cord-014597-66vd2mdu 1036 14 maintenance maintenance NN cord-014597-66vd2mdu 1036 15 cultures culture NNS cord-014597-66vd2mdu 1036 16 compared compare VBN cord-014597-66vd2mdu 1036 17 to to IN cord-014597-66vd2mdu 1036 18 working work VBG cord-014597-66vd2mdu 1036 19 volume volume NN cord-014597-66vd2mdu 1036 20 for for IN cord-014597-66vd2mdu 1036 21 microvesiclesupplementation microvesiclesupplementation NN cord-014597-66vd2mdu 1036 22 were be VBD cord-014597-66vd2mdu 1036 23 used use VBN cord-014597-66vd2mdu 1036 24 in in IN cord-014597-66vd2mdu 1036 25 each each DT cord-014597-66vd2mdu 1036 26 experiment experiment NN cord-014597-66vd2mdu 1036 27 . . . cord-014597-66vd2mdu 1037 1 The the DT cord-014597-66vd2mdu 1037 2 growth growth NN cord-014597-66vd2mdu 1037 3 of of IN cord-014597-66vd2mdu 1037 4 microvesicle microvesicle NNP cord-014597-66vd2mdu 1037 5 - - HYPH cord-014597-66vd2mdu 1037 6 supplemented supplement VBN cord-014597-66vd2mdu 1037 7 cultures culture NNS cord-014597-66vd2mdu 1037 8 had have VBD cord-014597-66vd2mdu 1037 9 shorter short JJR cord-014597-66vd2mdu 1037 10 lag lag NN cord-014597-66vd2mdu 1037 11 - - HYPH cord-014597-66vd2mdu 1037 12 phase phase NN cord-014597-66vd2mdu 1037 13 and and CC cord-014597-66vd2mdu 1037 14 achieved achieve VBD cord-014597-66vd2mdu 1037 15 1.2 1.2 CD cord-014597-66vd2mdu 1037 16 fold fold VB cord-014597-66vd2mdu 1037 17 higher high JJR cord-014597-66vd2mdu 1037 18 maximum maximum JJ cord-014597-66vd2mdu 1037 19 cell cell NN cord-014597-66vd2mdu 1037 20 density density NN cord-014597-66vd2mdu 1037 21 ( ( -LRB- cord-014597-66vd2mdu 1037 22 1.46x10 1.46x10 CD cord-014597-66vd2mdu 1037 23 6 6 CD cord-014597-66vd2mdu 1037 24 viable viable JJ cord-014597-66vd2mdu 1037 25 cells cell NNS cord-014597-66vd2mdu 1037 26 / / SYM cord-014597-66vd2mdu 1037 27 mL ml NN cord-014597-66vd2mdu 1037 28 ) ) -RRB- cord-014597-66vd2mdu 1037 29 compared compare VBN cord-014597-66vd2mdu 1037 30 to to IN cord-014597-66vd2mdu 1037 31 untreated untreated JJ cord-014597-66vd2mdu 1037 32 standard standard JJ cord-014597-66vd2mdu 1037 33 culture culture NN cord-014597-66vd2mdu 1037 34 ( ( -LRB- cord-014597-66vd2mdu 1037 35 1.21 1.21 CD cord-014597-66vd2mdu 1037 36 x10 x10 CD cord-014597-66vd2mdu 1037 37 6 6 CD cord-014597-66vd2mdu 1037 38 viable viable JJ cord-014597-66vd2mdu 1037 39 cells cell NNS cord-014597-66vd2mdu 1037 40 / / SYM cord-014597-66vd2mdu 1037 41 mL ml NN cord-014597-66vd2mdu 1037 42 ) ) -RRB- cord-014597-66vd2mdu 1037 43 and and CC cord-014597-66vd2mdu 1037 44 maintained maintain VBD cord-014597-66vd2mdu 1037 45 higher higher RBR cord-014597-66vd2mdu 1037 46 for for IN cord-014597-66vd2mdu 1037 47 the the DT cord-014597-66vd2mdu 1037 48 remaining remain VBG cord-014597-66vd2mdu 1037 49 period period NN cord-014597-66vd2mdu 1037 50 of of IN cord-014597-66vd2mdu 1037 51 batch batch NN cord-014597-66vd2mdu 1037 52 culture culture NN cord-014597-66vd2mdu 1038 1 ( ( -LRB- cord-014597-66vd2mdu 1038 2 Fig Fig NNP cord-014597-66vd2mdu 1038 3 . . . cord-014597-66vd2mdu 1038 4 1b 1b CD cord-014597-66vd2mdu 1038 5 ) ) -RRB- cord-014597-66vd2mdu 1038 6 . . . cord-014597-66vd2mdu 1039 1 However however RB cord-014597-66vd2mdu 1039 2 , , , cord-014597-66vd2mdu 1039 3 microvesicle microvesicle NNP cord-014597-66vd2mdu 1039 4 - - HYPH cord-014597-66vd2mdu 1039 5 free free JJ cord-014597-66vd2mdu 1039 6 fraction fraction NN cord-014597-66vd2mdu 1039 7 did do VBD cord-014597-66vd2mdu 1039 8 not not RB cord-014597-66vd2mdu 1039 9 had have VBD cord-014597-66vd2mdu 1039 10 significant significant JJ cord-014597-66vd2mdu 1039 11 impact impact NN cord-014597-66vd2mdu 1039 12 on on IN cord-014597-66vd2mdu 1039 13 growth growth NN cord-014597-66vd2mdu 1039 14 . . . cord-014597-66vd2mdu 1040 1 The the DT cord-014597-66vd2mdu 1040 2 viability viability NN cord-014597-66vd2mdu 1040 3 of of IN cord-014597-66vd2mdu 1040 4 microvesicle microvesicle NN cord-014597-66vd2mdu 1040 5 - - HYPH cord-014597-66vd2mdu 1040 6 supplemented supplement VBN cord-014597-66vd2mdu 1040 7 cultures culture NNS cord-014597-66vd2mdu 1040 8 , , , cord-014597-66vd2mdu 1040 9 similar similar JJ cord-014597-66vd2mdu 1040 10 to to IN cord-014597-66vd2mdu 1040 11 microvesicle microvesicle NNP cord-014597-66vd2mdu 1040 12 - - HYPH cord-014597-66vd2mdu 1040 13 free free JJ cord-014597-66vd2mdu 1040 14 media medium NNS cord-014597-66vd2mdu 1040 15 supplemented supplement VBN cord-014597-66vd2mdu 1040 16 , , , cord-014597-66vd2mdu 1040 17 was be VBD cord-014597-66vd2mdu 1040 18 also also RB cord-014597-66vd2mdu 1040 19 higher high JJR cord-014597-66vd2mdu 1040 20 compared compare VBN cord-014597-66vd2mdu 1040 21 to to IN cord-014597-66vd2mdu 1040 22 standard standard JJ cord-014597-66vd2mdu 1040 23 culture culture NN cord-014597-66vd2mdu 1040 24 suggesting suggest VBG cord-014597-66vd2mdu 1040 25 potential potential JJ cord-014597-66vd2mdu 1040 26 use use NN cord-014597-66vd2mdu 1040 27 of of IN cord-014597-66vd2mdu 1040 28 microvesicles microvesicle NNS cord-014597-66vd2mdu 1040 29 for for IN cord-014597-66vd2mdu 1040 30 regulating regulate VBG cord-014597-66vd2mdu 1040 31 CHO CHO NNP cord-014597-66vd2mdu 1040 32 growth growth NN cord-014597-66vd2mdu 1040 33 in in IN cord-014597-66vd2mdu 1040 34 production production NN cord-014597-66vd2mdu 1040 35 cultures culture NNS cord-014597-66vd2mdu 1040 36 . . . cord-014597-66vd2mdu 1041 1 This this DT cord-014597-66vd2mdu 1041 2 could could MD cord-014597-66vd2mdu 1041 3 be be VB cord-014597-66vd2mdu 1041 4 possibily possibily RB cord-014597-66vd2mdu 1041 5 because because IN cord-014597-66vd2mdu 1041 6 microvesicles microvesicle NNS cord-014597-66vd2mdu 1041 7 have have VBP cord-014597-66vd2mdu 1041 8 already already RB cord-014597-66vd2mdu 1041 9 been be VBN cord-014597-66vd2mdu 1041 10 reported report VBN cord-014597-66vd2mdu 1041 11 to to TO cord-014597-66vd2mdu 1041 12 be be VB cord-014597-66vd2mdu 1041 13 enriched enrich VBN cord-014597-66vd2mdu 1041 14 with with IN cord-014597-66vd2mdu 1041 15 cell cell NN cord-014597-66vd2mdu 1041 16 growth growth NN cord-014597-66vd2mdu 1041 17 / / SYM cord-014597-66vd2mdu 1041 18 death death NN cord-014597-66vd2mdu 1041 19 - - HYPH cord-014597-66vd2mdu 1041 20 regulating regulate VBG cord-014597-66vd2mdu 1041 21 proteins protein NNS cord-014597-66vd2mdu 1041 22 and and CC cord-014597-66vd2mdu 1041 23 hence hence RB cord-014597-66vd2mdu 1041 24 facilitating facilitate VBG cord-014597-66vd2mdu 1041 25 cell cell NN cord-014597-66vd2mdu 1041 26 growth growth NN cord-014597-66vd2mdu 1041 27 [ [ -LRB- cord-014597-66vd2mdu 1041 28 2 2 CD cord-014597-66vd2mdu 1041 29 , , , cord-014597-66vd2mdu 1041 30 3 3 CD cord-014597-66vd2mdu 1041 31 ] ] -RRB- cord-014597-66vd2mdu 1041 32 . . . cord-014597-66vd2mdu 1042 1 We -PRON- PRP cord-014597-66vd2mdu 1042 2 have have VBP cord-014597-66vd2mdu 1042 3 also also RB cord-014597-66vd2mdu 1042 4 observed observe VBN cord-014597-66vd2mdu 1042 5 abundance abundance NN cord-014597-66vd2mdu 1042 6 of of IN cord-014597-66vd2mdu 1042 7 cell cell NN cord-014597-66vd2mdu 1042 8 cycle cycle NN cord-014597-66vd2mdu 1042 9 regulators regulator NNS cord-014597-66vd2mdu 1042 10 including include VBG cord-014597-66vd2mdu 1042 11 cyclin cyclin NN cord-014597-66vd2mdu 1042 12 D1 d1 NN cord-014597-66vd2mdu 1042 13 in in IN cord-014597-66vd2mdu 1042 14 microvesicle microvesicle NN cord-014597-66vd2mdu 1042 15 - - HYPH cord-014597-66vd2mdu 1042 16 fraction fraction NN cord-014597-66vd2mdu 1042 17 compared compare VBN cord-014597-66vd2mdu 1042 18 to to IN cord-014597-66vd2mdu 1042 19 microvesicle microvesicle NNP cord-014597-66vd2mdu 1042 20 - - HYPH cord-014597-66vd2mdu 1042 21 free free JJ cord-014597-66vd2mdu 1042 22 spent spend VBN cord-014597-66vd2mdu 1042 23 - - HYPH cord-014597-66vd2mdu 1042 24 media medium NNS cord-014597-66vd2mdu 1042 25 in in IN cord-014597-66vd2mdu 1042 26 our -PRON- PRP$ cord-014597-66vd2mdu 1042 27 laboratory laboratory NN cord-014597-66vd2mdu 1042 28 ( ( -LRB- cord-014597-66vd2mdu 1042 29 data datum NNS cord-014597-66vd2mdu 1042 30 not not RB cord-014597-66vd2mdu 1042 31 shown show VBN cord-014597-66vd2mdu 1042 32 ) ) -RRB- cord-014597-66vd2mdu 1042 33 ; ; : cord-014597-66vd2mdu 1042 34 however however RB cord-014597-66vd2mdu 1042 35 , , , cord-014597-66vd2mdu 1042 36 further further JJ cord-014597-66vd2mdu 1042 37 investigation investigation NN cord-014597-66vd2mdu 1042 38 are be VBP cord-014597-66vd2mdu 1042 39 required require VBN cord-014597-66vd2mdu 1042 40 to to TO cord-014597-66vd2mdu 1042 41 prove prove VB cord-014597-66vd2mdu 1042 42 the the DT cord-014597-66vd2mdu 1042 43 hypothesis hypothesis NN cord-014597-66vd2mdu 1042 44 . . . cord-014597-66vd2mdu 1043 1 The the DT cord-014597-66vd2mdu 1043 2 overall overall JJ cord-014597-66vd2mdu 1043 3 productivity productivity NN cord-014597-66vd2mdu 1043 4 of of IN cord-014597-66vd2mdu 1043 5 human human JJ cord-014597-66vd2mdu 1043 6 IgG igg NN cord-014597-66vd2mdu 1043 7 secreting secrete VBG cord-014597-66vd2mdu 1043 8 CHO CHO NNP cord-014597-66vd2mdu 1043 9 cells cell NNS cord-014597-66vd2mdu 1043 10 was be VBD cord-014597-66vd2mdu 1043 11 also also RB cord-014597-66vd2mdu 1043 12 observed observe VBN cord-014597-66vd2mdu 1043 13 to to TO cord-014597-66vd2mdu 1043 14 increase increase VB cord-014597-66vd2mdu 1043 15 bỹ bỹ NN cord-014597-66vd2mdu 1043 16 4 4 CD cord-014597-66vd2mdu 1043 17 fold fold NN cord-014597-66vd2mdu 1043 18 following follow VBG cord-014597-66vd2mdu 1043 19 supplementation supplementation NN cord-014597-66vd2mdu 1043 20 of of IN cord-014597-66vd2mdu 1043 21 microvesicles microvesicle NNS cord-014597-66vd2mdu 1043 22 to to IN cord-014597-66vd2mdu 1043 23 the the DT cord-014597-66vd2mdu 1043 24 culture culture NN cord-014597-66vd2mdu 1043 25 without without IN cord-014597-66vd2mdu 1043 26 significantly significantly RB cord-014597-66vd2mdu 1043 27 affecting affect VBG cord-014597-66vd2mdu 1043 28 per per IN cord-014597-66vd2mdu 1043 29 - - HYPH cord-014597-66vd2mdu 1043 30 cell cell NN cord-014597-66vd2mdu 1043 31 productivity productivity NN cord-014597-66vd2mdu 1043 32 . . . cord-014597-66vd2mdu 1044 1 Since since IN cord-014597-66vd2mdu 1044 2 microvesicle microvesicle NN cord-014597-66vd2mdu 1044 3 - - HYPH cord-014597-66vd2mdu 1044 4 supplementation supplementation NN cord-014597-66vd2mdu 1044 5 facilitates facilitate VBZ cord-014597-66vd2mdu 1044 6 cell cell NN cord-014597-66vd2mdu 1044 7 growth growth NN cord-014597-66vd2mdu 1044 8 , , , cord-014597-66vd2mdu 1044 9 increased increase VBN cord-014597-66vd2mdu 1044 10 number number NN cord-014597-66vd2mdu 1044 11 of of IN cord-014597-66vd2mdu 1044 12 viable viable JJ cord-014597-66vd2mdu 1044 13 producer producer NN cord-014597-66vd2mdu 1044 14 cells cell NNS cord-014597-66vd2mdu 1044 15 in in IN cord-014597-66vd2mdu 1044 16 the the DT cord-014597-66vd2mdu 1044 17 culture culture NN cord-014597-66vd2mdu 1044 18 could could MD cord-014597-66vd2mdu 1044 19 be be VB cord-014597-66vd2mdu 1044 20 expected expect VBN cord-014597-66vd2mdu 1044 21 to to TO cord-014597-66vd2mdu 1044 22 be be VB cord-014597-66vd2mdu 1044 23 the the DT cord-014597-66vd2mdu 1044 24 basis basis NN cord-014597-66vd2mdu 1044 25 of of IN cord-014597-66vd2mdu 1044 26 observed observed JJ cord-014597-66vd2mdu 1044 27 increase increase NN cord-014597-66vd2mdu 1044 28 in in IN cord-014597-66vd2mdu 1044 29 the the DT cord-014597-66vd2mdu 1044 30 overall overall JJ cord-014597-66vd2mdu 1044 31 productivity productivity NN cord-014597-66vd2mdu 1044 32 of of IN cord-014597-66vd2mdu 1044 33 the the DT cord-014597-66vd2mdu 1044 34 culture culture NN cord-014597-66vd2mdu 1044 35 [ [ -LRB- cord-014597-66vd2mdu 1044 36 2 2 CD cord-014597-66vd2mdu 1044 37 , , , cord-014597-66vd2mdu 1044 38 3 3 CD cord-014597-66vd2mdu 1044 39 ] ] -RRB- cord-014597-66vd2mdu 1044 40 . . . cord-014597-66vd2mdu 1045 1 The the DT cord-014597-66vd2mdu 1045 2 further further JJ cord-014597-66vd2mdu 1045 3 work work NN cord-014597-66vd2mdu 1045 4 is be VBZ cord-014597-66vd2mdu 1045 5 ongoing ongoing JJ cord-014597-66vd2mdu 1045 6 to to IN cord-014597-66vd2mdu 1045 7 in in IN cord-014597-66vd2mdu 1045 8 - - HYPH cord-014597-66vd2mdu 1045 9 depth depth NN cord-014597-66vd2mdu 1045 10 explore explore VB cord-014597-66vd2mdu 1045 11 the the DT cord-014597-66vd2mdu 1045 12 potential potential NN cord-014597-66vd2mdu 1045 13 of of IN cord-014597-66vd2mdu 1045 14 microvesicles microvesicle NNS cord-014597-66vd2mdu 1045 15 for for IN cord-014597-66vd2mdu 1045 16 improving improve VBG cord-014597-66vd2mdu 1045 17 recombinant recombinant JJ cord-014597-66vd2mdu 1045 18 protein protein NN cord-014597-66vd2mdu 1045 19 production production NN cord-014597-66vd2mdu 1045 20 from from IN cord-014597-66vd2mdu 1045 21 CHO CHO NNP cord-014597-66vd2mdu 1045 22 cells cell NNS cord-014597-66vd2mdu 1045 23 . . . cord-014597-66vd2mdu 1046 1 The the DT cord-014597-66vd2mdu 1046 2 data datum NNS cord-014597-66vd2mdu 1046 3 indicate indicate VBP cord-014597-66vd2mdu 1046 4 that that IN cord-014597-66vd2mdu 1046 5 microvesicles microvesicle NNS cord-014597-66vd2mdu 1046 6 secreted secrete VBN cord-014597-66vd2mdu 1046 7 from from IN cord-014597-66vd2mdu 1046 8 CHO CHO NNP cord-014597-66vd2mdu 1046 9 cells cell NNS cord-014597-66vd2mdu 1046 10 can can MD cord-014597-66vd2mdu 1046 11 improve improve VB cord-014597-66vd2mdu 1046 12 cell cell NN cord-014597-66vd2mdu 1046 13 growth growth NN cord-014597-66vd2mdu 1046 14 and and CC cord-014597-66vd2mdu 1046 15 hence hence RB cord-014597-66vd2mdu 1046 16 recombinat recombinat NNP cord-014597-66vd2mdu 1046 17 protein protein NN cord-014597-66vd2mdu 1046 18 production production NN cord-014597-66vd2mdu 1046 19 in in IN cord-014597-66vd2mdu 1046 20 culture culture NN cord-014597-66vd2mdu 1046 21 . . . cord-014597-66vd2mdu 1047 1 Therefore therefore RB cord-014597-66vd2mdu 1047 2 , , , cord-014597-66vd2mdu 1047 3 strategies strategy NNS cord-014597-66vd2mdu 1047 4 need need VBP cord-014597-66vd2mdu 1047 5 to to TO cord-014597-66vd2mdu 1047 6 be be VB cord-014597-66vd2mdu 1047 7 developed develop VBN cord-014597-66vd2mdu 1047 8 for for IN cord-014597-66vd2mdu 1047 9 sterile sterile JJ cord-014597-66vd2mdu 1047 10 isolation isolation NN cord-014597-66vd2mdu 1047 11 of of IN cord-014597-66vd2mdu 1047 12 CHO CHO NNP cord-014597-66vd2mdu 1047 13 microvesicles microvesicle NNS cord-014597-66vd2mdu 1047 14 from from IN cord-014597-66vd2mdu 1047 15 routine routine JJ cord-014597-66vd2mdu 1047 16 maintenance maintenance NN cord-014597-66vd2mdu 1047 17 cultures culture NNS cord-014597-66vd2mdu 1047 18 and and CC cord-014597-66vd2mdu 1047 19 their -PRON- PRP$ cord-014597-66vd2mdu 1047 20 supplementation supplementation NN cord-014597-66vd2mdu 1047 21 into into IN cord-014597-66vd2mdu 1047 22 the the DT cord-014597-66vd2mdu 1047 23 production production NN cord-014597-66vd2mdu 1047 24 culture culture NN cord-014597-66vd2mdu 1047 25 for for IN cord-014597-66vd2mdu 1047 26 improving improve VBG cord-014597-66vd2mdu 1047 27 the the DT cord-014597-66vd2mdu 1047 28 performance performance NN cord-014597-66vd2mdu 1047 29 of of IN cord-014597-66vd2mdu 1047 30 CHO CHO NNP cord-014597-66vd2mdu 1047 31 - - HYPH cord-014597-66vd2mdu 1047 32 based base VBN cord-014597-66vd2mdu 1047 33 production production NN cord-014597-66vd2mdu 1047 34 process process NN cord-014597-66vd2mdu 1047 35 . . . cord-014597-66vd2mdu 1048 1 The the DT cord-014597-66vd2mdu 1048 2 glycosylation glycosylation NN cord-014597-66vd2mdu 1048 3 profile profile NN cord-014597-66vd2mdu 1048 4 of of IN cord-014597-66vd2mdu 1048 5 a a DT cord-014597-66vd2mdu 1048 6 recombinant recombinant JJ cord-014597-66vd2mdu 1048 7 protein protein NN cord-014597-66vd2mdu 1048 8 is be VBZ cord-014597-66vd2mdu 1048 9 one one CD cord-014597-66vd2mdu 1048 10 of of IN cord-014597-66vd2mdu 1048 11 the the DT cord-014597-66vd2mdu 1048 12 most most RBS cord-014597-66vd2mdu 1048 13 important important JJ cord-014597-66vd2mdu 1048 14 attributes attribute NNS cord-014597-66vd2mdu 1048 15 when when WRB cord-014597-66vd2mdu 1048 16 defining define VBG cord-014597-66vd2mdu 1048 17 product product NN cord-014597-66vd2mdu 1048 18 quality quality NN cord-014597-66vd2mdu 1048 19 . . . cord-014597-66vd2mdu 1049 1 Producing produce VBG cord-014597-66vd2mdu 1049 2 a a DT cord-014597-66vd2mdu 1049 3 protein protein NN cord-014597-66vd2mdu 1049 4 with with IN cord-014597-66vd2mdu 1049 5 desired desire VBN cord-014597-66vd2mdu 1049 6 characteristics characteristic NNS cord-014597-66vd2mdu 1049 7 requires require VBZ cord-014597-66vd2mdu 1049 8 the the DT cord-014597-66vd2mdu 1049 9 ability ability NN cord-014597-66vd2mdu 1049 10 to to TO cord-014597-66vd2mdu 1049 11 modify modify VB cord-014597-66vd2mdu 1049 12 and and CC cord-014597-66vd2mdu 1049 13 target target VB cord-014597-66vd2mdu 1049 14 specific specific JJ cord-014597-66vd2mdu 1049 15 glycosylation glycosylation NN cord-014597-66vd2mdu 1049 16 profiles profile NNS cord-014597-66vd2mdu 1049 17 . . . cord-014597-66vd2mdu 1050 1 Traditionally traditionally RB cord-014597-66vd2mdu 1050 2 the the DT cord-014597-66vd2mdu 1050 3 approach approach NN cord-014597-66vd2mdu 1050 4 to to TO cord-014597-66vd2mdu 1050 5 modify modify VB cord-014597-66vd2mdu 1050 6 the the DT cord-014597-66vd2mdu 1050 7 glycosylation glycosylation NN cord-014597-66vd2mdu 1050 8 profile profile NN cord-014597-66vd2mdu 1050 9 of of IN cord-014597-66vd2mdu 1050 10 a a DT cord-014597-66vd2mdu 1050 11 protein protein NN cord-014597-66vd2mdu 1050 12 involves involve VBZ cord-014597-66vd2mdu 1050 13 supplementing supplement VBG cord-014597-66vd2mdu 1050 14 a a DT cord-014597-66vd2mdu 1050 15 culture culture NN cord-014597-66vd2mdu 1050 16 with with IN cord-014597-66vd2mdu 1050 17 components component NNS cord-014597-66vd2mdu 1050 18 that that WDT cord-014597-66vd2mdu 1050 19 can can MD cord-014597-66vd2mdu 1050 20 improve improve VB cord-014597-66vd2mdu 1050 21 galactosylation galactosylation NN cord-014597-66vd2mdu 1050 22 . . . cord-014597-66vd2mdu 1051 1 Experimentation experimentation NN cord-014597-66vd2mdu 1051 2 using use VBG cord-014597-66vd2mdu 1051 3 this this DT cord-014597-66vd2mdu 1051 4 supplemental supplemental JJ cord-014597-66vd2mdu 1051 5 approach approach NN cord-014597-66vd2mdu 1051 6 resulted result VBD cord-014597-66vd2mdu 1051 7 in in IN cord-014597-66vd2mdu 1051 8 a a DT cord-014597-66vd2mdu 1051 9 dramatic dramatic JJ cord-014597-66vd2mdu 1051 10 increase increase NN cord-014597-66vd2mdu 1051 11 in in IN cord-014597-66vd2mdu 1051 12 terminal terminal JJ cord-014597-66vd2mdu 1051 13 galactosylation galactosylation NN cord-014597-66vd2mdu 1051 14 , , , cord-014597-66vd2mdu 1051 15 but but CC cord-014597-66vd2mdu 1051 16 lacked lack VBD cord-014597-66vd2mdu 1051 17 the the DT cord-014597-66vd2mdu 1051 18 ability ability NN cord-014597-66vd2mdu 1051 19 to to TO cord-014597-66vd2mdu 1051 20 easily easily RB cord-014597-66vd2mdu 1051 21 and and CC cord-014597-66vd2mdu 1051 22 repeatedly repeatedly RB cord-014597-66vd2mdu 1051 23 target target VB cord-014597-66vd2mdu 1051 24 specific specific JJ cord-014597-66vd2mdu 1051 25 glycosylation glycosylation NN cord-014597-66vd2mdu 1051 26 profiles profile NNS cord-014597-66vd2mdu 1051 27 . . . cord-014597-66vd2mdu 1052 1 Using use VBG cord-014597-66vd2mdu 1052 2 novel novel JJ cord-014597-66vd2mdu 1052 3 and and CC cord-014597-66vd2mdu 1052 4 proprietary proprietary JJ cord-014597-66vd2mdu 1052 5 technology technology NN cord-014597-66vd2mdu 1052 6 , , , cord-014597-66vd2mdu 1052 7 we -PRON- PRP cord-014597-66vd2mdu 1052 8 have have VBP cord-014597-66vd2mdu 1052 9 developed develop VBN cord-014597-66vd2mdu 1052 10 a a DT cord-014597-66vd2mdu 1052 11 feed feed NN cord-014597-66vd2mdu 1052 12 ( ( -LRB- cord-014597-66vd2mdu 1052 13 GlycanTune GlycanTune NNP cord-014597-66vd2mdu 1052 14 ™ ™ NN cord-014597-66vd2mdu 1052 15 ) ) -RRB- cord-014597-66vd2mdu 1052 16 and and CC cord-014597-66vd2mdu 1052 17 a a DT cord-014597-66vd2mdu 1052 18 unique unique JJ cord-014597-66vd2mdu 1052 19 feeding feeding NN cord-014597-66vd2mdu 1052 20 process process NN cord-014597-66vd2mdu 1052 21 that that WDT cord-014597-66vd2mdu 1052 22 will will MD cord-014597-66vd2mdu 1052 23 maximize maximize VB cord-014597-66vd2mdu 1052 24 growth growth NN cord-014597-66vd2mdu 1052 25 and and CC cord-014597-66vd2mdu 1052 26 titer titer NN cord-014597-66vd2mdu 1052 27 while while IN cord-014597-66vd2mdu 1052 28 being be VBG cord-014597-66vd2mdu 1052 29 able able JJ cord-014597-66vd2mdu 1052 30 to to TO cord-014597-66vd2mdu 1052 31 modulate modulate VB cord-014597-66vd2mdu 1052 32 glycan glycan NN cord-014597-66vd2mdu 1052 33 profiles profile NNS cord-014597-66vd2mdu 1052 34 . . . cord-014597-66vd2mdu 1053 1 This this DT cord-014597-66vd2mdu 1053 2 new new JJ cord-014597-66vd2mdu 1053 3 feed feed NN cord-014597-66vd2mdu 1053 4 can can MD cord-014597-66vd2mdu 1053 5 be be VB cord-014597-66vd2mdu 1053 6 added add VBN cord-014597-66vd2mdu 1053 7 as as IN cord-014597-66vd2mdu 1053 8 a a DT cord-014597-66vd2mdu 1053 9 standalone standalone JJ cord-014597-66vd2mdu 1053 10 process process NN cord-014597-66vd2mdu 1053 11 that that WDT cord-014597-66vd2mdu 1053 12 can can MD cord-014597-66vd2mdu 1053 13 result result VB cord-014597-66vd2mdu 1053 14 in in IN cord-014597-66vd2mdu 1053 15 a a DT cord-014597-66vd2mdu 1053 16 significant significant JJ cord-014597-66vd2mdu 1053 17 shift shift NN cord-014597-66vd2mdu 1053 18 from from IN cord-014597-66vd2mdu 1053 19 G0F g0f NN cord-014597-66vd2mdu 1053 20 to to IN cord-014597-66vd2mdu 1053 21 G1F g1f NN cord-014597-66vd2mdu 1053 22 and and CC cord-014597-66vd2mdu 1053 23 G2F g2f LS cord-014597-66vd2mdu 1053 24 ( ( -LRB- cord-014597-66vd2mdu 1053 25 maximum maximum JJ cord-014597-66vd2mdu 1053 26 galactosylation galactosylation NN cord-014597-66vd2mdu 1053 27 ) ) -RRB- cord-014597-66vd2mdu 1053 28 . . . cord-014597-66vd2mdu 1054 1 Using use VBG cord-014597-66vd2mdu 1054 2 a a DT cord-014597-66vd2mdu 1054 3 unique unique JJ cord-014597-66vd2mdu 1054 4 fed fed JJ cord-014597-66vd2mdu 1054 5 - - HYPH cord-014597-66vd2mdu 1054 6 batch batch NN cord-014597-66vd2mdu 1054 7 process process NN cord-014597-66vd2mdu 1054 8 , , , cord-014597-66vd2mdu 1054 9 GlycanTune GlycanTune NNP cord-014597-66vd2mdu 1054 10 can can MD cord-014597-66vd2mdu 1054 11 also also RB cord-014597-66vd2mdu 1054 12 be be VB cord-014597-66vd2mdu 1054 13 used use VBN cord-014597-66vd2mdu 1054 14 with with IN cord-014597-66vd2mdu 1054 15 a a DT cord-014597-66vd2mdu 1054 16 standard standard JJ cord-014597-66vd2mdu 1054 17 feed feed NN cord-014597-66vd2mdu 1054 18 to to TO cord-014597-66vd2mdu 1054 19 dial dial VB cord-014597-66vd2mdu 1054 20 in in IN cord-014597-66vd2mdu 1054 21 targeted target VBN cord-014597-66vd2mdu 1054 22 glycosylation glycosylation NN cord-014597-66vd2mdu 1054 23 profiles profile NNS cord-014597-66vd2mdu 1054 24 . . . cord-014597-66vd2mdu 1055 1 Through through IN cord-014597-66vd2mdu 1055 2 process process NN cord-014597-66vd2mdu 1055 3 development development NN cord-014597-66vd2mdu 1055 4 , , , cord-014597-66vd2mdu 1055 5 we -PRON- PRP cord-014597-66vd2mdu 1055 6 created create VBD cord-014597-66vd2mdu 1055 7 a a DT cord-014597-66vd2mdu 1055 8 method method NN cord-014597-66vd2mdu 1055 9 where where WRB cord-014597-66vd2mdu 1055 10 a a DT cord-014597-66vd2mdu 1055 11 transition transition NN cord-014597-66vd2mdu 1055 12 point point NN cord-014597-66vd2mdu 1055 13 is be VBZ cord-014597-66vd2mdu 1055 14 used use VBN cord-014597-66vd2mdu 1055 15 to to TO cord-014597-66vd2mdu 1055 16 switch switch VB cord-014597-66vd2mdu 1055 17 from from IN cord-014597-66vd2mdu 1055 18 a a DT cord-014597-66vd2mdu 1055 19 standard standard JJ cord-014597-66vd2mdu 1055 20 feed feed NN cord-014597-66vd2mdu 1055 21 to to IN cord-014597-66vd2mdu 1055 22 a a DT cord-014597-66vd2mdu 1055 23 glycan glycan NN cord-014597-66vd2mdu 1055 24 modulating modulate VBG cord-014597-66vd2mdu 1055 25 feed feed NN cord-014597-66vd2mdu 1055 26 . . . cord-014597-66vd2mdu 1056 1 The the DT cord-014597-66vd2mdu 1056 2 timing timing NN cord-014597-66vd2mdu 1056 3 of of IN cord-014597-66vd2mdu 1056 4 the the DT cord-014597-66vd2mdu 1056 5 transition transition NN cord-014597-66vd2mdu 1056 6 point point NN cord-014597-66vd2mdu 1056 7 will will MD cord-014597-66vd2mdu 1056 8 determine determine VB cord-014597-66vd2mdu 1056 9 the the DT cord-014597-66vd2mdu 1056 10 specificity specificity NN cord-014597-66vd2mdu 1056 11 of of IN cord-014597-66vd2mdu 1056 12 the the DT cord-014597-66vd2mdu 1056 13 glycan glycan NN cord-014597-66vd2mdu 1056 14 profile profile NN cord-014597-66vd2mdu 1056 15 . . . cord-014597-66vd2mdu 1056 16 ) ) -RRB- cord-014597-66vd2mdu 1056 17 . . . cord-014597-66vd2mdu 1057 1 N n CD cord-014597-66vd2mdu 1057 2 - - HYPH cord-014597-66vd2mdu 1057 3 linked link VBN cord-014597-66vd2mdu 1057 4 glycans glycan NNS cord-014597-66vd2mdu 1057 5 were be VBD cord-014597-66vd2mdu 1057 6 digested digest VBN cord-014597-66vd2mdu 1057 7 with with IN cord-014597-66vd2mdu 1057 8 PNGase PNGase NNP cord-014597-66vd2mdu 1057 9 F F NNP cord-014597-66vd2mdu 1057 10 and and CC cord-014597-66vd2mdu 1057 11 quantified quantify VBD cord-014597-66vd2mdu 1057 12 using use VBG cord-014597-66vd2mdu 1057 13 100pmole 100pmole NNP cord-014597-66vd2mdu 1057 14 maltohexose maltohexose NNP cord-014597-66vd2mdu 1057 15 / / SYM cord-014597-66vd2mdu 1057 16 maltopentose maltopentose NNP cord-014597-66vd2mdu 1057 17 internal internal JJ cord-014597-66vd2mdu 1057 18 standards standard NNS cord-014597-66vd2mdu 1057 19 labeled label VBN cord-014597-66vd2mdu 1057 20 with with IN cord-014597-66vd2mdu 1057 21 8-aminopyrene-1,3,6-trisulfonic 8-aminopyrene-1,3,6-trisulfonic CD cord-014597-66vd2mdu 1057 22 acid acid NN cord-014597-66vd2mdu 1057 23 ( ( -LRB- cord-014597-66vd2mdu 1057 24 ATPS ATPS NNP cord-014597-66vd2mdu 1057 25 ) ) -RRB- cord-014597-66vd2mdu 1057 26 as as IN cord-014597-66vd2mdu 1057 27 described describe VBN cord-014597-66vd2mdu 1057 28 by by IN cord-014597-66vd2mdu 1057 29 Laroy Laroy NNP cord-014597-66vd2mdu 1057 30 et et FW cord-014597-66vd2mdu 1057 31 al al NNP cord-014597-66vd2mdu 1057 32 [ [ -LRB- cord-014597-66vd2mdu 1057 33 1 1 CD cord-014597-66vd2mdu 1057 34 ] ] -RRB- cord-014597-66vd2mdu 1057 35 or or CC cord-014597-66vd2mdu 1057 36 the the DT cord-014597-66vd2mdu 1057 37 user user NN cord-014597-66vd2mdu 1057 38 guide guide NN cord-014597-66vd2mdu 1057 39 for for IN cord-014597-66vd2mdu 1057 40 the the DT cord-014597-66vd2mdu 1057 41 Glycan Glycan NNP cord-014597-66vd2mdu 1057 42 Labeling Labeling NNP cord-014597-66vd2mdu 1057 43 and and CC cord-014597-66vd2mdu 1057 44 Analysis Analysis NNP cord-014597-66vd2mdu 1057 45 Kit kit NN cord-014597-66vd2mdu 1057 46 ( ( -LRB- cord-014597-66vd2mdu 1057 47 GlycanAssure GlycanAssure NNP cord-014597-66vd2mdu 1057 48 ™ ™ NN cord-014597-66vd2mdu 1057 49 user user NN cord-014597-66vd2mdu 1057 50 guide guide NN cord-014597-66vd2mdu 1057 51 , , , cord-014597-66vd2mdu 1057 52 Thermo Thermo NNP cord-014597-66vd2mdu 1057 53 Fisher Fisher NNP cord-014597-66vd2mdu 1057 54 Scientific Scientific NNP cord-014597-66vd2mdu 1057 55 ) ) -RRB- cord-014597-66vd2mdu 1057 56 . . . cord-014597-66vd2mdu 1058 1 All all DT cord-014597-66vd2mdu 1058 2 CE CE NNP cord-014597-66vd2mdu 1058 3 separations separation NNS cord-014597-66vd2mdu 1058 4 were be VBD cord-014597-66vd2mdu 1058 5 performed perform VBN cord-014597-66vd2mdu 1058 6 using use VBG cord-014597-66vd2mdu 1058 7 the the DT cord-014597-66vd2mdu 1058 8 Applied Applied NNP cord-014597-66vd2mdu 1058 9 Biosystems Biosystems NNP cord-014597-66vd2mdu 1058 10 ™ ™ CD cord-014597-66vd2mdu 1058 11 3500xL. 3500xl. CD cord-014597-66vd2mdu 1059 1 The the DT cord-014597-66vd2mdu 1059 2 timing timing NN cord-014597-66vd2mdu 1059 3 of of IN cord-014597-66vd2mdu 1059 4 transition transition NN cord-014597-66vd2mdu 1059 5 from from IN cord-014597-66vd2mdu 1059 6 EFC+ EFC+ NNP cord-014597-66vd2mdu 1059 7 to to IN cord-014597-66vd2mdu 1059 8 GTC+ GTC+ NNP cord-014597-66vd2mdu 1059 9 made make VBD cord-014597-66vd2mdu 1059 10 it -PRON- PRP cord-014597-66vd2mdu 1059 11 possible possible JJ cord-014597-66vd2mdu 1059 12 to to TO cord-014597-66vd2mdu 1059 13 target target VB cord-014597-66vd2mdu 1059 14 specific specific JJ cord-014597-66vd2mdu 1059 15 glycosylation glycosylation NN cord-014597-66vd2mdu 1059 16 profiles profile NNS cord-014597-66vd2mdu 1059 17 . . . cord-014597-66vd2mdu 1060 1 Modulating modulate VBG cord-014597-66vd2mdu 1060 2 G0F G0F NNS cord-014597-66vd2mdu 1060 3 from from IN cord-014597-66vd2mdu 1060 4 75 75 CD cord-014597-66vd2mdu 1060 5 % % NN cord-014597-66vd2mdu 1060 6 down down RB cord-014597-66vd2mdu 1060 7 to to IN cord-014597-66vd2mdu 1060 8 32 32 CD cord-014597-66vd2mdu 1060 9 % % NN cord-014597-66vd2mdu 1060 10 , , , cord-014597-66vd2mdu 1060 11 while while IN cord-014597-66vd2mdu 1060 12 increasing increase VBG cord-014597-66vd2mdu 1060 13 G1F g1f RB cord-014597-66vd2mdu 1060 14 and and CC cord-014597-66vd2mdu 1060 15 increasing increase VBG cord-014597-66vd2mdu 1060 16 G2F G2F NNS cord-014597-66vd2mdu 1060 17 ( ( -LRB- cord-014597-66vd2mdu 1060 18 Fig Fig NNP cord-014597-66vd2mdu 1060 19 . . . cord-014597-66vd2mdu 1060 20 1 1 CD cord-014597-66vd2mdu 1060 21 ) ) -RRB- cord-014597-66vd2mdu 1060 22 . . . cord-014597-66vd2mdu 1061 1 Transitioning transition VBG cord-014597-66vd2mdu 1061 2 to to IN cord-014597-66vd2mdu 1061 3 GTC+ GTC+ NNS cord-014597-66vd2mdu 1061 4 early early RB cord-014597-66vd2mdu 1061 5 in in IN cord-014597-66vd2mdu 1061 6 culture culture NN cord-014597-66vd2mdu 1061 7 resulted result VBD cord-014597-66vd2mdu 1061 8 in in IN cord-014597-66vd2mdu 1061 9 a a DT cord-014597-66vd2mdu 1061 10 greater great JJR cord-014597-66vd2mdu 1061 11 shift shift NN cord-014597-66vd2mdu 1061 12 from from IN cord-014597-66vd2mdu 1061 13 G0F g0f NN cord-014597-66vd2mdu 1061 14 to to IN cord-014597-66vd2mdu 1061 15 G1F g1f CD cord-014597-66vd2mdu 1061 16 and and CC cord-014597-66vd2mdu 1061 17 G2F. G2F. NNP cord-014597-66vd2mdu 1061 18 Transitioning transition VBG cord-014597-66vd2mdu 1061 19 midway midway RB cord-014597-66vd2mdu 1061 20 or or CC cord-014597-66vd2mdu 1061 21 late late RB cord-014597-66vd2mdu 1061 22 in in IN cord-014597-66vd2mdu 1061 23 culture culture NN cord-014597-66vd2mdu 1061 24 resulted result VBD cord-014597-66vd2mdu 1061 25 in in IN cord-014597-66vd2mdu 1061 26 a a DT cord-014597-66vd2mdu 1061 27 greater great JJR cord-014597-66vd2mdu 1061 28 proportion proportion NN cord-014597-66vd2mdu 1061 29 of of IN cord-014597-66vd2mdu 1061 30 G0F g0f NN cord-014597-66vd2mdu 1061 31 compared compare VBN cord-014597-66vd2mdu 1061 32 to to IN cord-014597-66vd2mdu 1061 33 G1F g1f NN cord-014597-66vd2mdu 1061 34 and and CC cord-014597-66vd2mdu 1061 35 G2F. G2F. NNP cord-014597-66vd2mdu 1061 36 Supplementation Supplementation NNP cord-014597-66vd2mdu 1061 37 based base VBN cord-014597-66vd2mdu 1061 38 approaches approach NNS cord-014597-66vd2mdu 1061 39 using use VBG cord-014597-66vd2mdu 1061 40 glycosylation glycosylation NN cord-014597-66vd2mdu 1061 41 modulating modulate VBG cord-014597-66vd2mdu 1061 42 media medium NNS cord-014597-66vd2mdu 1061 43 components component NNS cord-014597-66vd2mdu 1061 44 to to TO cord-014597-66vd2mdu 1061 45 modify modify VB cord-014597-66vd2mdu 1061 46 and and CC cord-014597-66vd2mdu 1061 47 target target VB cord-014597-66vd2mdu 1061 48 specific specific JJ cord-014597-66vd2mdu 1061 49 glycosylation glycosylation NN cord-014597-66vd2mdu 1061 50 profiles profile NNS cord-014597-66vd2mdu 1061 51 proved prove VBD cord-014597-66vd2mdu 1061 52 to to TO cord-014597-66vd2mdu 1061 53 be be VB cord-014597-66vd2mdu 1061 54 difficult difficult JJ cord-014597-66vd2mdu 1061 55 . . . cord-014597-66vd2mdu 1062 1 These these DT cord-014597-66vd2mdu 1062 2 approaches approach NNS cord-014597-66vd2mdu 1062 3 were be VBD cord-014597-66vd2mdu 1062 4 able able JJ cord-014597-66vd2mdu 1062 5 to to TO cord-014597-66vd2mdu 1062 6 increase increase VB cord-014597-66vd2mdu 1062 7 terminal terminal JJ cord-014597-66vd2mdu 1062 8 galactosylation galactosylation NN cord-014597-66vd2mdu 1062 9 ( ( -LRB- cord-014597-66vd2mdu 1062 10 G1F g1f NN cord-014597-66vd2mdu 1062 11 and and CC cord-014597-66vd2mdu 1062 12 G2F G2F NNP cord-014597-66vd2mdu 1062 13 ) ) -RRB- cord-014597-66vd2mdu 1062 14 , , , cord-014597-66vd2mdu 1062 15 but but CC cord-014597-66vd2mdu 1062 16 lacked lack VBD cord-014597-66vd2mdu 1062 17 the the DT cord-014597-66vd2mdu 1062 18 ability ability NN cord-014597-66vd2mdu 1062 19 to to TO cord-014597-66vd2mdu 1062 20 fine fine VB cord-014597-66vd2mdu 1062 21 tune tune NN cord-014597-66vd2mdu 1062 22 glycan glycan NN cord-014597-66vd2mdu 1062 23 profiles profile NNS cord-014597-66vd2mdu 1062 24 . . . cord-014597-66vd2mdu 1063 1 This this DT cord-014597-66vd2mdu 1063 2 could could MD cord-014597-66vd2mdu 1063 3 result result VB cord-014597-66vd2mdu 1063 4 in in IN cord-014597-66vd2mdu 1063 5 numerous numerous JJ cord-014597-66vd2mdu 1063 6 rounds round NNS cord-014597-66vd2mdu 1063 7 of of IN cord-014597-66vd2mdu 1063 8 titration titration NN cord-014597-66vd2mdu 1063 9 experiments experiment NNS cord-014597-66vd2mdu 1063 10 to to TO cord-014597-66vd2mdu 1063 11 target target VB cord-014597-66vd2mdu 1063 12 specific specific JJ cord-014597-66vd2mdu 1063 13 glycan glycan NN cord-014597-66vd2mdu 1063 14 profiles profile NNS cord-014597-66vd2mdu 1063 15 that that WDT cord-014597-66vd2mdu 1063 16 would would MD cord-014597-66vd2mdu 1063 17 likely likely RB cord-014597-66vd2mdu 1063 18 remain remain VB cord-014597-66vd2mdu 1063 19 inconsistent inconsistent JJ cord-014597-66vd2mdu 1063 20 between between IN cord-014597-66vd2mdu 1063 21 cell cell NN cord-014597-66vd2mdu 1063 22 lines line NNS cord-014597-66vd2mdu 1063 23 , , , cord-014597-66vd2mdu 1063 24 culture culture NN cord-014597-66vd2mdu 1063 25 media medium NNS cord-014597-66vd2mdu 1063 26 and and CC cord-014597-66vd2mdu 1063 27 feeds feed NNS cord-014597-66vd2mdu 1063 28 , , , cord-014597-66vd2mdu 1063 29 and and CC cord-014597-66vd2mdu 1063 30 process process NN cord-014597-66vd2mdu 1063 31 scale scale NN cord-014597-66vd2mdu 1063 32 . . . cord-014597-66vd2mdu 1064 1 The the DT cord-014597-66vd2mdu 1064 2 development development NN cord-014597-66vd2mdu 1064 3 of of IN cord-014597-66vd2mdu 1064 4 a a DT cord-014597-66vd2mdu 1064 5 unique unique JJ cord-014597-66vd2mdu 1064 6 process process NN cord-014597-66vd2mdu 1064 7 made make VBD cord-014597-66vd2mdu 1064 8 it -PRON- PRP cord-014597-66vd2mdu 1064 9 possible possible JJ cord-014597-66vd2mdu 1064 10 to to TO cord-014597-66vd2mdu 1064 11 predictably predictably RB cord-014597-66vd2mdu 1064 12 target target VB cord-014597-66vd2mdu 1064 13 specific specific JJ cord-014597-66vd2mdu 1064 14 glycosylation glycosylation NN cord-014597-66vd2mdu 1064 15 profiles profile NNS cord-014597-66vd2mdu 1064 16 . . . cord-014597-66vd2mdu 1065 1 Transition transition NN cord-014597-66vd2mdu 1065 2 from from IN cord-014597-66vd2mdu 1065 3 standard standard JJ cord-014597-66vd2mdu 1065 4 feeding feeding NN cord-014597-66vd2mdu 1065 5 to to IN cord-014597-66vd2mdu 1065 6 GlycanTune GlycanTune NNP cord-014597-66vd2mdu 1065 7 allowed allow VBN cord-014597-66vd2mdu 1065 8 for for IN cord-014597-66vd2mdu 1065 9 precise precise JJ cord-014597-66vd2mdu 1065 10 targeting targeting NN cord-014597-66vd2mdu 1065 11 of of IN cord-014597-66vd2mdu 1065 12 glycan glycan NN cord-014597-66vd2mdu 1065 13 profiles profile NNS cord-014597-66vd2mdu 1065 14 . . . cord-014597-66vd2mdu 1066 1 Transition transition NN cord-014597-66vd2mdu 1066 2 to to IN cord-014597-66vd2mdu 1066 3 GlycanTune GlycanTune NNP cord-014597-66vd2mdu 1066 4 early early RB cord-014597-66vd2mdu 1066 5 in in IN cord-014597-66vd2mdu 1066 6 culture culture NN cord-014597-66vd2mdu 1066 7 resulted result VBD cord-014597-66vd2mdu 1066 8 in in IN cord-014597-66vd2mdu 1066 9 an an DT cord-014597-66vd2mdu 1066 10 increased increased JJ cord-014597-66vd2mdu 1066 11 shift shift NN cord-014597-66vd2mdu 1066 12 from from IN cord-014597-66vd2mdu 1066 13 G0F g0f NN cord-014597-66vd2mdu 1066 14 to to IN cord-014597-66vd2mdu 1066 15 G1F g1f CD cord-014597-66vd2mdu 1066 16 and and CC cord-014597-66vd2mdu 1066 17 G2F. G2F. NNP cord-014597-66vd2mdu 1066 18 A a DT cord-014597-66vd2mdu 1066 19 transition transition NN cord-014597-66vd2mdu 1066 20 late late RB cord-014597-66vd2mdu 1066 21 in in IN cord-014597-66vd2mdu 1066 22 culture culture NN cord-014597-66vd2mdu 1066 23 resulted result VBD cord-014597-66vd2mdu 1066 24 in in IN cord-014597-66vd2mdu 1066 25 increased increase VBN cord-014597-66vd2mdu 1066 26 G0F g0f NN cord-014597-66vd2mdu 1066 27 and and CC cord-014597-66vd2mdu 1066 28 decreased decrease VBD cord-014597-66vd2mdu 1066 29 G1F g1f RB cord-014597-66vd2mdu 1066 30 and and CC cord-014597-66vd2mdu 1066 31 G2F. G2F. NNP cord-014597-66vd2mdu 1066 32 _SP cord-014597-66vd2mdu 1066 33 Growth Growth NNP cord-014597-66vd2mdu 1066 34 performance performance NN cord-014597-66vd2mdu 1066 35 during during IN cord-014597-66vd2mdu 1066 36 precultures preculture NNS cord-014597-66vd2mdu 1066 37 and and CC cord-014597-66vd2mdu 1066 38 batch batch NN cord-014597-66vd2mdu 1066 39 curves curve NNS cord-014597-66vd2mdu 1066 40 in in IN cord-014597-66vd2mdu 1066 41 plain plain JJ cord-014597-66vd2mdu 1066 42 shaking shaking NN cord-014597-66vd2mdu 1066 43 flasks flask NNS cord-014597-66vd2mdu 1066 44 did do VBD cord-014597-66vd2mdu 1066 45 not not RB cord-014597-66vd2mdu 1066 46 show show VB cord-014597-66vd2mdu 1066 47 any any DT cord-014597-66vd2mdu 1066 48 differences difference NNS cord-014597-66vd2mdu 1066 49 among among IN cord-014597-66vd2mdu 1066 50 tested test VBN cord-014597-66vd2mdu 1066 51 surfactants surfactant NNS cord-014597-66vd2mdu 1066 52 or or CC cord-014597-66vd2mdu 1066 53 lots lot NNS cord-014597-66vd2mdu 1066 54 thereof thereof RB cord-014597-66vd2mdu 1066 55 , , , cord-014597-66vd2mdu 1066 56 and and CC cord-014597-66vd2mdu 1066 57 cell cell NN cord-014597-66vd2mdu 1066 58 densities density NNS cord-014597-66vd2mdu 1066 59 reached reach VBD cord-014597-66vd2mdu 1066 60 10 10 CD cord-014597-66vd2mdu 1066 61 - - SYM cord-014597-66vd2mdu 1066 62 12·10 12·10 CD cord-014597-66vd2mdu 1066 63 6 6 CD cord-014597-66vd2mdu 1066 64 cells/ cells/ CD cord-014597-66vd2mdu 1066 65 mL ml NN cord-014597-66vd2mdu 1067 1 ( ( -LRB- cord-014597-66vd2mdu 1067 2 Fig Fig NNP cord-014597-66vd2mdu 1067 3 . . . cord-014597-66vd2mdu 1067 4 1a 1a CD cord-014597-66vd2mdu 1067 5 and and CC cord-014597-66vd2mdu 1067 6 b b LS cord-014597-66vd2mdu 1067 7 ) ) -RRB- cord-014597-66vd2mdu 1067 8 . . . cord-014597-66vd2mdu 1068 1 Experiments experiment NNS cord-014597-66vd2mdu 1068 2 with with IN cord-014597-66vd2mdu 1068 3 HEK HEK NNP cord-014597-66vd2mdu 1068 4 293-F 293-f CD cord-014597-66vd2mdu 1068 5 cells cell NNS cord-014597-66vd2mdu 1068 6 at at IN cord-014597-66vd2mdu 1068 7 elevated elevated JJ cord-014597-66vd2mdu 1068 8 power power NN cord-014597-66vd2mdu 1068 9 input input NN cord-014597-66vd2mdu 1068 10 in in IN cord-014597-66vd2mdu 1068 11 baffled baffled JJ cord-014597-66vd2mdu 1068 12 shaking shake VBG cord-014597-66vd2mdu 1068 13 flasks flask NNS cord-014597-66vd2mdu 1068 14 revealed reveal VBD cord-014597-66vd2mdu 1068 15 distinct distinct JJ cord-014597-66vd2mdu 1068 16 differences difference NNS cord-014597-66vd2mdu 1068 17 between between IN cord-014597-66vd2mdu 1068 18 Pluronic Pluronic NNP cord-014597-66vd2mdu 1068 19 ® ® . cord-014597-66vd2mdu 1068 20 F-68 F-68 NNP cord-014597-66vd2mdu 1068 21 , , , cord-014597-66vd2mdu 1068 22 F-127 f-127 NN cord-014597-66vd2mdu 1068 23 and and CC cord-014597-66vd2mdu 1068 24 Kolliphor Kolliphor NNP cord-014597-66vd2mdu 1068 25 ® ® , cord-014597-66vd2mdu 1068 26 P188 P188 NNP cord-014597-66vd2mdu 1068 27 , , , cord-014597-66vd2mdu 1068 28 with with IN cord-014597-66vd2mdu 1068 29 F-127 f-127 NN cord-014597-66vd2mdu 1068 30 showing show VBG cord-014597-66vd2mdu 1068 31 the the DT cord-014597-66vd2mdu 1068 32 best good JJS cord-014597-66vd2mdu 1068 33 performance performance NN cord-014597-66vd2mdu 1068 34 . . . cord-014597-66vd2mdu 1069 1 Peak peak JJ cord-014597-66vd2mdu 1069 2 viable viable JJ cord-014597-66vd2mdu 1069 3 cell cell NN cord-014597-66vd2mdu 1069 4 densities density NNS cord-014597-66vd2mdu 1069 5 reached reach VBN cord-014597-66vd2mdu 1069 6 with with IN cord-014597-66vd2mdu 1069 7 lots lot NNS cord-014597-66vd2mdu 1069 8 A a NN cord-014597-66vd2mdu 1069 9 and and CC cord-014597-66vd2mdu 1069 10 B b NN cord-014597-66vd2mdu 1069 11 of of IN cord-014597-66vd2mdu 1069 12 Pluronic Pluronic NNP cord-014597-66vd2mdu 1069 13 ® ® . cord-014597-66vd2mdu 1069 14 F-68 F-68 NNP cord-014597-66vd2mdu 1069 15 and and CC cord-014597-66vd2mdu 1069 16 F-127 f-127 NN cord-014597-66vd2mdu 1069 17 were be VBD cord-014597-66vd2mdu 1069 18 comparable comparable JJ cord-014597-66vd2mdu 1069 19 to to IN cord-014597-66vd2mdu 1069 20 those those DT cord-014597-66vd2mdu 1069 21 in in IN cord-014597-66vd2mdu 1069 22 plain plain JJ cord-014597-66vd2mdu 1069 23 shaking shaking NN cord-014597-66vd2mdu 1069 24 flasks flask NNS cord-014597-66vd2mdu 1069 25 , , , cord-014597-66vd2mdu 1069 26 while while IN cord-014597-66vd2mdu 1069 27 those those DT cord-014597-66vd2mdu 1069 28 for for IN cord-014597-66vd2mdu 1069 29 Kolliphor Kolliphor NNP cord-014597-66vd2mdu 1069 30 ® ® POS cord-014597-66vd2mdu 1069 31 P188 P188 NNP cord-014597-66vd2mdu 1069 32 and and CC cord-014597-66vd2mdu 1069 33 lots lot NNS cord-014597-66vd2mdu 1069 34 C c NN cord-014597-66vd2mdu 1069 35 and and CC cord-014597-66vd2mdu 1069 36 D d NN cord-014597-66vd2mdu 1069 37 of of IN cord-014597-66vd2mdu 1069 38 Pluronic Pluronic NNP cord-014597-66vd2mdu 1070 1 ® ® , cord-014597-66vd2mdu 1070 2 F-68 F-68 NNP cord-014597-66vd2mdu 1070 3 were be VBD cord-014597-66vd2mdu 1070 4 significantly significantly RB cord-014597-66vd2mdu 1070 5 lower low JJR cord-014597-66vd2mdu 1070 6 . . . cord-014597-66vd2mdu 1071 1 Peak Peak NNP cord-014597-66vd2mdu 1071 2 viale viale NN cord-014597-66vd2mdu 1071 3 cell cell NN cord-014597-66vd2mdu 1071 4 densities density NNS cord-014597-66vd2mdu 1071 5 were be VBD cord-014597-66vd2mdu 1071 6 of of IN cord-014597-66vd2mdu 1071 7 2 2 CD cord-014597-66vd2mdu 1071 8 -12·10 -12·10 SYM cord-014597-66vd2mdu 1071 9 6 6 CD cord-014597-66vd2mdu 1071 10 cells cell NNS cord-014597-66vd2mdu 1071 11 / / SYM cord-014597-66vd2mdu 1071 12 mL ml NN cord-014597-66vd2mdu 1072 1 ( ( -LRB- cord-014597-66vd2mdu 1072 2 Fig Fig NNP cord-014597-66vd2mdu 1072 3 . . . cord-014597-66vd2mdu 1072 4 1c 1c CD cord-014597-66vd2mdu 1072 5 ) ) -RRB- cord-014597-66vd2mdu 1072 6 . . . cord-014597-66vd2mdu 1073 1 Similar similar JJ cord-014597-66vd2mdu 1073 2 transient transient JJ cord-014597-66vd2mdu 1073 3 transfection transfection NN cord-014597-66vd2mdu 1073 4 efficiency efficiency NN cord-014597-66vd2mdu 1073 5 and and CC cord-014597-66vd2mdu 1073 6 mean mean VB cord-014597-66vd2mdu 1073 7 fluorescence fluorescence NN cord-014597-66vd2mdu 1073 8 of of IN cord-014597-66vd2mdu 1073 9 transfected transfecte VBN cord-014597-66vd2mdu 1073 10 cells cell NNS cord-014597-66vd2mdu 1073 11 independent independent JJ cord-014597-66vd2mdu 1073 12 of of IN cord-014597-66vd2mdu 1073 13 applied applied JJ cord-014597-66vd2mdu 1073 14 surfactant surfactant NN cord-014597-66vd2mdu 1073 15 and and CC cord-014597-66vd2mdu 1073 16 lot lot NN cord-014597-66vd2mdu 1073 17 thereof thereof RB cord-014597-66vd2mdu 1073 18 indicated indicate VBD cord-014597-66vd2mdu 1073 19 no no DT cord-014597-66vd2mdu 1073 20 major major JJ cord-014597-66vd2mdu 1073 21 impact impact NN cord-014597-66vd2mdu 1073 22 of of IN cord-014597-66vd2mdu 1073 23 respective respective JJ cord-014597-66vd2mdu 1073 24 poloxamer poloxamer NN cord-014597-66vd2mdu 1073 25 ( ( -LRB- cord-014597-66vd2mdu 1073 26 Fig Fig NNP cord-014597-66vd2mdu 1073 27 . . . cord-014597-66vd2mdu 1073 28 1d 1d CD cord-014597-66vd2mdu 1073 29 ) ) -RRB- cord-014597-66vd2mdu 1073 30 . . . cord-014597-66vd2mdu 1074 1 Interestingly interestingly RB cord-014597-66vd2mdu 1074 2 , , , cord-014597-66vd2mdu 1074 3 experiments experiment NNS cord-014597-66vd2mdu 1074 4 using use VBG cord-014597-66vd2mdu 1074 5 fluorescein fluorescein NN cord-014597-66vd2mdu 1074 6 - - HYPH cord-014597-66vd2mdu 1074 7 labelled label VBN cord-014597-66vd2mdu 1074 8 Pluronic Pluronic NNP cord-014597-66vd2mdu 1074 9 ® ® NNS cord-014597-66vd2mdu 1074 10 showed show VBD cord-014597-66vd2mdu 1074 11 a a DT cord-014597-66vd2mdu 1074 12 time time NN cord-014597-66vd2mdu 1074 13 - - HYPH cord-014597-66vd2mdu 1074 14 dependent dependent JJ cord-014597-66vd2mdu 1074 15 uptake uptake NN cord-014597-66vd2mdu 1074 16 into into IN cord-014597-66vd2mdu 1074 17 HEK HEK NNP cord-014597-66vd2mdu 1074 18 cells cell NNS cord-014597-66vd2mdu 1074 19 . . . cord-014597-66vd2mdu 1075 1 Visual visual JJ cord-014597-66vd2mdu 1075 2 tracking tracking NN cord-014597-66vd2mdu 1075 3 revealed reveal VBD cord-014597-66vd2mdu 1075 4 an an DT cord-014597-66vd2mdu 1075 5 endocytic endocytic JJ cord-014597-66vd2mdu 1075 6 uptake uptake NN cord-014597-66vd2mdu 1075 7 of of IN cord-014597-66vd2mdu 1075 8 poloxamers poloxamer NNS cord-014597-66vd2mdu 1075 9 by by IN cord-014597-66vd2mdu 1075 10 the the DT cord-014597-66vd2mdu 1075 11 cells cell NNS cord-014597-66vd2mdu 1075 12 ( ( -LRB- cord-014597-66vd2mdu 1075 13 > > XX cord-014597-66vd2mdu 1076 1 10fold 10fold CD cord-014597-66vd2mdu 1076 2 increase increase NN cord-014597-66vd2mdu 1076 3 in in IN cord-014597-66vd2mdu 1076 4 signal signal NN cord-014597-66vd2mdu 1076 5 after after IN cord-014597-66vd2mdu 1076 6 96 96 CD cord-014597-66vd2mdu 1076 7 h h NN cord-014597-66vd2mdu 1076 8 ) ) -RRB- cord-014597-66vd2mdu 1076 9 and and CC cord-014597-66vd2mdu 1076 10 its -PRON- PRP$ cord-014597-66vd2mdu 1076 11 co co NN cord-014597-66vd2mdu 1076 12 - - NN cord-014597-66vd2mdu 1076 13 localisation localisation NN cord-014597-66vd2mdu 1076 14 with with IN cord-014597-66vd2mdu 1076 15 cell cell NN cord-014597-66vd2mdu 1076 16 membrane membrane NN cord-014597-66vd2mdu 1076 17 and and CC cord-014597-66vd2mdu 1076 18 lysosomes lysosome NNS cord-014597-66vd2mdu 1076 19 . . . cord-014597-66vd2mdu 1077 1 SEC SEC NNP cord-014597-66vd2mdu 1077 2 ( ( -LRB- cord-014597-66vd2mdu 1077 3 Fig Fig NNP cord-014597-66vd2mdu 1077 4 . . . cord-014597-66vd2mdu 1077 5 1e 1e LS cord-014597-66vd2mdu 1077 6 ) ) -RRB- cord-014597-66vd2mdu 1078 1 analyses analysis NNS cord-014597-66vd2mdu 1078 2 showed show VBD cord-014597-66vd2mdu 1078 3 differences difference NNS cord-014597-66vd2mdu 1078 4 between between IN cord-014597-66vd2mdu 1078 5 the the DT cord-014597-66vd2mdu 1078 6 tested test VBN cord-014597-66vd2mdu 1078 7 poloxamers poloxamer NNS cord-014597-66vd2mdu 1078 8 . . . cord-014597-66vd2mdu 1079 1 Especially especially RB cord-014597-66vd2mdu 1079 2 tested test VBN cord-014597-66vd2mdu 1079 3 lots lot NNS cord-014597-66vd2mdu 1079 4 of of IN cord-014597-66vd2mdu 1079 5 Pluronic Pluronic NNP cord-014597-66vd2mdu 1080 1 ® ® , cord-014597-66vd2mdu 1080 2 F-68 F-68 NNP cord-014597-66vd2mdu 1080 3 revealed reveal VBD cord-014597-66vd2mdu 1080 4 notable notable JJ cord-014597-66vd2mdu 1080 5 deviations deviation NNS cord-014597-66vd2mdu 1080 6 in in IN cord-014597-66vd2mdu 1080 7 the the DT cord-014597-66vd2mdu 1080 8 low low JJ cord-014597-66vd2mdu 1080 9 molecular molecular JJ cord-014597-66vd2mdu 1080 10 weight weight NN cord-014597-66vd2mdu 1080 11 fraction fraction NN cord-014597-66vd2mdu 1080 12 ( ( -LRB- cord-014597-66vd2mdu 1080 13 peak peak NNP cord-014597-66vd2mdu 1080 14 2 2 CD cord-014597-66vd2mdu 1080 15 , , , cord-014597-66vd2mdu 1080 16 Fig Fig NNP cord-014597-66vd2mdu 1080 17 . . . cord-014597-66vd2mdu 1080 18 1e 1e NNP cord-014597-66vd2mdu 1080 19 ) ) -RRB- cord-014597-66vd2mdu 1080 20 , , , cord-014597-66vd2mdu 1080 21 compared compare VBN cord-014597-66vd2mdu 1080 22 to to IN cord-014597-66vd2mdu 1080 23 the the DT cord-014597-66vd2mdu 1080 24 other other JJ cord-014597-66vd2mdu 1080 25 poloxamers poloxamer NNS cord-014597-66vd2mdu 1080 26 . . . cord-014597-66vd2mdu 1081 1 Cultures culture NNS cord-014597-66vd2mdu 1081 2 subjected subject VBN cord-014597-66vd2mdu 1081 3 to to IN cord-014597-66vd2mdu 1081 4 varying vary VBG cord-014597-66vd2mdu 1081 5 levels level NNS cord-014597-66vd2mdu 1081 6 of of IN cord-014597-66vd2mdu 1081 7 shear shear NN cord-014597-66vd2mdu 1081 8 stress stress NN cord-014597-66vd2mdu 1081 9 showed show VBD cord-014597-66vd2mdu 1081 10 distinct distinct JJ cord-014597-66vd2mdu 1081 11 growth growth NN cord-014597-66vd2mdu 1081 12 differences difference NNS cord-014597-66vd2mdu 1081 13 depending depend VBG cord-014597-66vd2mdu 1081 14 on on IN cord-014597-66vd2mdu 1081 15 used use VBN cord-014597-66vd2mdu 1081 16 poloxamer poloxamer NN cord-014597-66vd2mdu 1081 17 . . . cord-014597-66vd2mdu 1082 1 While while IN cord-014597-66vd2mdu 1082 2 experiments experiment NNS cord-014597-66vd2mdu 1082 3 in in IN cord-014597-66vd2mdu 1082 4 plain plain JJ cord-014597-66vd2mdu 1082 5 shake shake NN cord-014597-66vd2mdu 1082 6 flasks flask NNS cord-014597-66vd2mdu 1082 7 did do VBD cord-014597-66vd2mdu 1082 8 not not RB cord-014597-66vd2mdu 1082 9 show show VB cord-014597-66vd2mdu 1082 10 any any DT cord-014597-66vd2mdu 1082 11 differences difference NNS cord-014597-66vd2mdu 1082 12 in in IN cord-014597-66vd2mdu 1082 13 growth growth NN cord-014597-66vd2mdu 1082 14 , , , cord-014597-66vd2mdu 1082 15 cultivations cultivation NNS cord-014597-66vd2mdu 1082 16 under under IN cord-014597-66vd2mdu 1082 17 elevated elevated JJ cord-014597-66vd2mdu 1082 18 shear shear NN cord-014597-66vd2mdu 1082 19 stress stress NN cord-014597-66vd2mdu 1082 20 in in IN cord-014597-66vd2mdu 1082 21 baffled baffled JJ cord-014597-66vd2mdu 1082 22 shake shake NN cord-014597-66vd2mdu 1082 23 flasks flask NNS cord-014597-66vd2mdu 1082 24 resulted result VBD cord-014597-66vd2mdu 1082 25 in in IN cord-014597-66vd2mdu 1082 26 lower low JJR cord-014597-66vd2mdu 1082 27 peak peak JJ cord-014597-66vd2mdu 1082 28 viable viable JJ cord-014597-66vd2mdu 1082 29 cell cell NN cord-014597-66vd2mdu 1082 30 densities density NNS cord-014597-66vd2mdu 1082 31 with with IN cord-014597-66vd2mdu 1082 32 Kolliphor Kolliphor NNP cord-014597-66vd2mdu 1083 1 ® ® NNP cord-014597-66vd2mdu 1083 2 P188 P188 NNP cord-014597-66vd2mdu 1083 3 and and CC cord-014597-66vd2mdu 1083 4 some some DT cord-014597-66vd2mdu 1083 5 Pluronic Pluronic NNP cord-014597-66vd2mdu 1084 1 ® ® . cord-014597-66vd2mdu 1085 1 F-68 F-68 NNP cord-014597-66vd2mdu 1085 2 lots lot NNS cord-014597-66vd2mdu 1085 3 . . . cord-014597-66vd2mdu 1086 1 It -PRON- PRP cord-014597-66vd2mdu 1086 2 remaines remain VBZ cord-014597-66vd2mdu 1086 3 unclear unclear JJ cord-014597-66vd2mdu 1086 4 whether whether IN cord-014597-66vd2mdu 1086 5 this this DT cord-014597-66vd2mdu 1086 6 can can MD cord-014597-66vd2mdu 1086 7 be be VB cord-014597-66vd2mdu 1086 8 explained explain VBN cord-014597-66vd2mdu 1086 9 by by IN cord-014597-66vd2mdu 1086 10 different different JJ cord-014597-66vd2mdu 1086 11 membrane membrane NN cord-014597-66vd2mdu 1086 12 protective protective JJ cord-014597-66vd2mdu 1086 13 activities activity NNS cord-014597-66vd2mdu 1086 14 alone alone RB cord-014597-66vd2mdu 1086 15 , , , cord-014597-66vd2mdu 1086 16 or or CC cord-014597-66vd2mdu 1086 17 if if IN cord-014597-66vd2mdu 1086 18 other other JJ cord-014597-66vd2mdu 1086 19 mechanisms mechanism NNS cord-014597-66vd2mdu 1086 20 , , , cord-014597-66vd2mdu 1086 21 occuring occur VBG cord-014597-66vd2mdu 1086 22 during during IN cord-014597-66vd2mdu 1086 23 and and CC cord-014597-66vd2mdu 1086 24 after after IN cord-014597-66vd2mdu 1086 25 cellular cellular JJ cord-014597-66vd2mdu 1086 26 uptake uptake NN cord-014597-66vd2mdu 1086 27 , , , cord-014597-66vd2mdu 1086 28 contribute contribute VBP cord-014597-66vd2mdu 1086 29 to to IN cord-014597-66vd2mdu 1086 30 this this DT cord-014597-66vd2mdu 1086 31 effect effect NN cord-014597-66vd2mdu 1086 32 . . . cord-014597-66vd2mdu 1087 1 Especially especially RB cord-014597-66vd2mdu 1087 2 for for IN cord-014597-66vd2mdu 1087 3 the the DT cord-014597-66vd2mdu 1087 4 tested test VBN cord-014597-66vd2mdu 1087 5 lots lot NNS cord-014597-66vd2mdu 1087 6 of of IN cord-014597-66vd2mdu 1087 7 Pluronic Pluronic NNP cord-014597-66vd2mdu 1087 8 ® ® . cord-014597-66vd2mdu 1087 9 F-68 F-68 NNP cord-014597-66vd2mdu 1087 10 , , , cord-014597-66vd2mdu 1087 11 SEC SEC NNP cord-014597-66vd2mdu 1087 12 of of IN cord-014597-66vd2mdu 1087 13 surfactants surfactant NNS cord-014597-66vd2mdu 1087 14 showed show VBD cord-014597-66vd2mdu 1087 15 differences difference NNS cord-014597-66vd2mdu 1087 16 in in IN cord-014597-66vd2mdu 1087 17 the the DT cord-014597-66vd2mdu 1087 18 low low JJ cord-014597-66vd2mdu 1087 19 molecular molecular JJ cord-014597-66vd2mdu 1087 20 weight weight NN cord-014597-66vd2mdu 1087 21 fraction fraction NN cord-014597-66vd2mdu 1087 22 . . . cord-014597-66vd2mdu 1088 1 This this DT cord-014597-66vd2mdu 1088 2 fraction fraction NN cord-014597-66vd2mdu 1088 3 mainly mainly RB cord-014597-66vd2mdu 1088 4 represents represent VBZ cord-014597-66vd2mdu 1088 5 polyethylen polyethylen NN cord-014597-66vd2mdu 1088 6 oxide oxide NN cord-014597-66vd2mdu 1088 7 ( ( -LRB- cord-014597-66vd2mdu 1088 8 PEO PEO NNP cord-014597-66vd2mdu 1088 9 ) ) -RRB- cord-014597-66vd2mdu 1088 10 ( ( -LRB- cord-014597-66vd2mdu 1088 11 revealed reveal VBN cord-014597-66vd2mdu 1088 12 by by IN cord-014597-66vd2mdu 1088 13 NMR NMR NNP cord-014597-66vd2mdu 1088 14 ) ) -RRB- cord-014597-66vd2mdu 1088 15 , , , cord-014597-66vd2mdu 1088 16 which which WDT cord-014597-66vd2mdu 1088 17 is be VBZ cord-014597-66vd2mdu 1088 18 likely likely JJ cord-014597-66vd2mdu 1088 19 to to TO cord-014597-66vd2mdu 1088 20 be be VB cord-014597-66vd2mdu 1088 21 a a DT cord-014597-66vd2mdu 1088 22 remnant remnant NN cord-014597-66vd2mdu 1088 23 from from IN cord-014597-66vd2mdu 1088 24 synthesis synthesis NN cord-014597-66vd2mdu 1088 25 . . . cord-014597-66vd2mdu 1089 1 These these DT cord-014597-66vd2mdu 1089 2 observations observation NNS cord-014597-66vd2mdu 1089 3 indicate indicate VBP cord-014597-66vd2mdu 1089 4 that that IN cord-014597-66vd2mdu 1089 5 the the DT cord-014597-66vd2mdu 1089 6 use use NN cord-014597-66vd2mdu 1089 7 of of IN cord-014597-66vd2mdu 1089 8 different different JJ cord-014597-66vd2mdu 1089 9 poloxamers poloxamer NNS cord-014597-66vd2mdu 1089 10 and and CC cord-014597-66vd2mdu 1089 11 lots lot NNS cord-014597-66vd2mdu 1089 12 thereof thereof RB cord-014597-66vd2mdu 1089 13 should should MD cord-014597-66vd2mdu 1089 14 be be VB cord-014597-66vd2mdu 1089 15 carefully carefully RB cord-014597-66vd2mdu 1089 16 evaluated evaluate VBN cord-014597-66vd2mdu 1089 17 , , , cord-014597-66vd2mdu 1089 18 especially especially RB cord-014597-66vd2mdu 1089 19 under under IN cord-014597-66vd2mdu 1089 20 elevated elevated JJ cord-014597-66vd2mdu 1089 21 shear shear NN cord-014597-66vd2mdu 1089 22 stress stress NN cord-014597-66vd2mdu 1089 23 . . . cord-014597-66vd2mdu 1090 1 Further further JJ cord-014597-66vd2mdu 1090 2 experiments experiment NNS cord-014597-66vd2mdu 1090 3 will will MD cord-014597-66vd2mdu 1090 4 focus focus VB cord-014597-66vd2mdu 1090 5 on on IN cord-014597-66vd2mdu 1090 6 investigating investigate VBG cord-014597-66vd2mdu 1090 7 distinct distinct JJ cord-014597-66vd2mdu 1090 8 SEC SEC NNP cord-014597-66vd2mdu 1090 9 fractions fraction NNS cord-014597-66vd2mdu 1090 10 of of IN cord-014597-66vd2mdu 1090 11 poloxamers poloxamer NNS cord-014597-66vd2mdu 1090 12 . . . cord-014597-66vd2mdu 1091 1 Overcoming overcome VBG cord-014597-66vd2mdu 1091 2 ( ( -LRB- cord-014597-66vd2mdu 1091 3 Fig Fig NNP cord-014597-66vd2mdu 1091 4 . . . cord-014597-66vd2mdu 1091 5 1 1 CD cord-014597-66vd2mdu 1091 6 ) ) -RRB- cord-014597-66vd2mdu 1091 7 . . . cord-014597-66vd2mdu 1092 1 Aurintricarboxylic Aurintricarboxylic NNP cord-014597-66vd2mdu 1092 2 acid acid NN cord-014597-66vd2mdu 1092 3 ( ( -LRB- cord-014597-66vd2mdu 1092 4 endonuclease endonuclease NN cord-014597-66vd2mdu 1092 5 inhibitor inhibitor NN cord-014597-66vd2mdu 1092 6 ; ; : cord-014597-66vd2mdu 1092 7 enhancer enhancer NN cord-014597-66vd2mdu 1092 8 used use VBN cord-014597-66vd2mdu 1092 9 in in IN cord-014597-66vd2mdu 1092 10 e.g. e.g. JJ cord-014597-66vd2mdu 1092 11 salivary salivary NN cord-014597-66vd2mdu 1092 12 gland gland NN cord-014597-66vd2mdu 1092 13 transfection transfection NN cord-014597-66vd2mdu 1092 14 ) ) -RRB- cord-014597-66vd2mdu 1092 15 and and CC cord-014597-66vd2mdu 1092 16 polyvinylpyrrolidone polyvinylpyrrolidone NNP cord-014597-66vd2mdu 1092 17 ( ( -LRB- cord-014597-66vd2mdu 1092 18 polymer polymer NN cord-014597-66vd2mdu 1092 19 ; ; , cord-014597-66vd2mdu 1092 20 beneficial beneficial JJ cord-014597-66vd2mdu 1092 21 in in IN cord-014597-66vd2mdu 1092 22 electroporation electroporation NN cord-014597-66vd2mdu 1092 23 ) ) -RRB- cord-014597-66vd2mdu 1092 24 were be VBD cord-014597-66vd2mdu 1092 25 both both DT cord-014597-66vd2mdu 1092 26 found find VBN cord-014597-66vd2mdu 1092 27 to to TO cord-014597-66vd2mdu 1092 28 negatively negatively RB cord-014597-66vd2mdu 1092 29 impact impact VB cord-014597-66vd2mdu 1092 30 PEImediated peimediate VBN cord-014597-66vd2mdu 1092 31 transfection transfection NN cord-014597-66vd2mdu 1092 32 of of IN cord-014597-66vd2mdu 1092 33 CHO CHO NNP cord-014597-66vd2mdu 1092 34 cells cell NNS cord-014597-66vd2mdu 1092 35 , , , cord-014597-66vd2mdu 1092 36 while while IN cord-014597-66vd2mdu 1092 37 another another DT cord-014597-66vd2mdu 1092 38 tested test VBN cord-014597-66vd2mdu 1092 39 polymer polymer NN cord-014597-66vd2mdu 1092 40 enhanced enhance VBN cord-014597-66vd2mdu 1092 41 growth growth NN cord-014597-66vd2mdu 1092 42 as as RB cord-014597-66vd2mdu 1092 43 well well RB cord-014597-66vd2mdu 1092 44 as as IN cord-014597-66vd2mdu 1092 45 transfection transfection NN cord-014597-66vd2mdu 1092 46 efficiency efficiency NN cord-014597-66vd2mdu 1092 47 . . . cord-014597-66vd2mdu 1093 1 The the DT cord-014597-66vd2mdu 1093 2 use use NN cord-014597-66vd2mdu 1093 3 of of IN cord-014597-66vd2mdu 1093 4 a a DT cord-014597-66vd2mdu 1093 5 strong strong JJ cord-014597-66vd2mdu 1093 6 chelator chelator NN cord-014597-66vd2mdu 1093 7 led lead VBD cord-014597-66vd2mdu 1093 8 to to IN cord-014597-66vd2mdu 1093 9 a a DT cord-014597-66vd2mdu 1093 10 high high JJ cord-014597-66vd2mdu 1093 11 transfection transfection NN cord-014597-66vd2mdu 1093 12 efficiency efficiency NN cord-014597-66vd2mdu 1093 13 , , , cord-014597-66vd2mdu 1093 14 but but CC cord-014597-66vd2mdu 1093 15 impaired impaired JJ cord-014597-66vd2mdu 1093 16 cell cell NN cord-014597-66vd2mdu 1093 17 growth growth NN cord-014597-66vd2mdu 1093 18 . . . cord-014597-66vd2mdu 1094 1 Based base VBN cord-014597-66vd2mdu 1094 2 on on IN cord-014597-66vd2mdu 1094 3 the the DT cord-014597-66vd2mdu 1094 4 results result NNS cord-014597-66vd2mdu 1094 5 of of IN cord-014597-66vd2mdu 1094 6 the the DT cord-014597-66vd2mdu 1094 7 independent independent JJ cord-014597-66vd2mdu 1094 8 substance substance NN cord-014597-66vd2mdu 1094 9 testings testing NNS cord-014597-66vd2mdu 1094 10 , , , cord-014597-66vd2mdu 1094 11 the the DT cord-014597-66vd2mdu 1094 12 medium medium JJ cord-014597-66vd2mdu 1094 13 formulation formulation NN cord-014597-66vd2mdu 1094 14 was be VBD cord-014597-66vd2mdu 1094 15 modified modify VBN cord-014597-66vd2mdu 1094 16 by by IN cord-014597-66vd2mdu 1094 17 the the DT cord-014597-66vd2mdu 1094 18 addition addition NN cord-014597-66vd2mdu 1094 19 of of IN cord-014597-66vd2mdu 1094 20 a a DT cord-014597-66vd2mdu 1094 21 weak weak JJ cord-014597-66vd2mdu 1094 22 chelator chelator NN cord-014597-66vd2mdu 1094 23 and and CC cord-014597-66vd2mdu 1094 24 further further JJ cord-014597-66vd2mdu 1094 25 components component NNS cord-014597-66vd2mdu 1094 26 including include VBG cord-014597-66vd2mdu 1094 27 vitamins vitamin NNS cord-014597-66vd2mdu 1094 28 . . . cord-014597-66vd2mdu 1095 1 Different different JJ cord-014597-66vd2mdu 1095 2 osmolalities osmolalitie NNS cord-014597-66vd2mdu 1095 3 between between IN cord-014597-66vd2mdu 1095 4 280 280 CD cord-014597-66vd2mdu 1095 5 mOsmol mOsmol NNP cord-014597-66vd2mdu 1095 6 / / SYM cord-014597-66vd2mdu 1095 7 kg kg NN cord-014597-66vd2mdu 1095 8 and and CC cord-014597-66vd2mdu 1095 9 340 340 CD cord-014597-66vd2mdu 1095 10 mOsmol mOsmol NNP cord-014597-66vd2mdu 1095 11 / / SYM cord-014597-66vd2mdu 1095 12 kg kg NNS cord-014597-66vd2mdu 1095 13 were be VBD cord-014597-66vd2mdu 1095 14 tested test VBN cord-014597-66vd2mdu 1095 15 for for IN cord-014597-66vd2mdu 1095 16 the the DT cord-014597-66vd2mdu 1095 17 final final JJ cord-014597-66vd2mdu 1095 18 formulation formulation NN cord-014597-66vd2mdu 1095 19 , , , cord-014597-66vd2mdu 1095 20 but but CC cord-014597-66vd2mdu 1095 21 no no DT cord-014597-66vd2mdu 1095 22 major major JJ cord-014597-66vd2mdu 1095 23 impact impact NN cord-014597-66vd2mdu 1095 24 was be VBD cord-014597-66vd2mdu 1095 25 seen see VBN cord-014597-66vd2mdu 1095 26 neither neither CC cord-014597-66vd2mdu 1095 27 on on IN cord-014597-66vd2mdu 1095 28 transfection transfection NN cord-014597-66vd2mdu 1095 29 efficiency efficiency NN cord-014597-66vd2mdu 1095 30 nor nor CC cord-014597-66vd2mdu 1095 31 on on IN cord-014597-66vd2mdu 1095 32 viability viability NN cord-014597-66vd2mdu 1095 33 2 2 CD cord-014597-66vd2mdu 1095 34 days day NNS cord-014597-66vd2mdu 1095 35 post post NN cord-014597-66vd2mdu 1095 36 - - NN cord-014597-66vd2mdu 1095 37 transfection transfection NN cord-014597-66vd2mdu 1095 38 . . . cord-014597-66vd2mdu 1096 1 The the DT cord-014597-66vd2mdu 1096 2 final final JJ cord-014597-66vd2mdu 1096 3 CHO CHO NNP cord-014597-66vd2mdu 1096 4 TF TF NNP cord-014597-66vd2mdu 1096 5 medium medium NN cord-014597-66vd2mdu 1096 6 formulation formulation NN cord-014597-66vd2mdu 1096 7 supported support VBD cord-014597-66vd2mdu 1096 8 high high JJ cord-014597-66vd2mdu 1096 9 cell cell NN cord-014597-66vd2mdu 1096 10 growth growth NN cord-014597-66vd2mdu 1096 11 of of IN cord-014597-66vd2mdu 1096 12 finally finally RB cord-014597-66vd2mdu 1096 13 tested test VBN cord-014597-66vd2mdu 1096 14 CHO CHO NNP cord-014597-66vd2mdu 1096 15 cell cell NN cord-014597-66vd2mdu 1096 16 lines line NNS cord-014597-66vd2mdu 1096 17 2 2 CD cord-014597-66vd2mdu 1096 18 and and CC cord-014597-66vd2mdu 1096 19 3 3 CD cord-014597-66vd2mdu 1096 20 with with IN cord-014597-66vd2mdu 1096 21 peak peak JJ cord-014597-66vd2mdu 1096 22 viable viable JJ cord-014597-66vd2mdu 1096 23 cell cell NN cord-014597-66vd2mdu 1096 24 densities density NNS cord-014597-66vd2mdu 1096 25 above above IN cord-014597-66vd2mdu 1096 26 10⋅10 10⋅10 CD cord-014597-66vd2mdu 1096 27 6 6 CD cord-014597-66vd2mdu 1096 28 cells cell NNS cord-014597-66vd2mdu 1096 29 / / SYM cord-014597-66vd2mdu 1096 30 ml ml NNS cord-014597-66vd2mdu 1096 31 in in IN cord-014597-66vd2mdu 1096 32 batch batch NN cord-014597-66vd2mdu 1096 33 cultivations cultivation NNS cord-014597-66vd2mdu 1096 34 with with IN cord-014597-66vd2mdu 1096 35 an an DT cord-014597-66vd2mdu 1096 36 overall overall JJ cord-014597-66vd2mdu 1096 37 cultivation cultivation NN cord-014597-66vd2mdu 1096 38 time time NN cord-014597-66vd2mdu 1096 39 of of IN cord-014597-66vd2mdu 1096 40 7 7 CD cord-014597-66vd2mdu 1096 41 - - SYM cord-014597-66vd2mdu 1096 42 8 8 CD cord-014597-66vd2mdu 1096 43 days day NNS cord-014597-66vd2mdu 1096 44 ( ( -LRB- cord-014597-66vd2mdu 1096 45 Fig fig NN cord-014597-66vd2mdu 1096 46 . . . cord-014597-66vd2mdu 1096 47 1 1 CD cord-014597-66vd2mdu 1096 48 ) ) -RRB- cord-014597-66vd2mdu 1096 49 . . . cord-014597-66vd2mdu 1097 1 Further further JJ cord-014597-66vd2mdu 1097 2 improvements improvement NNS cord-014597-66vd2mdu 1097 3 of of IN cord-014597-66vd2mdu 1097 4 the the DT cord-014597-66vd2mdu 1097 5 process process NN cord-014597-66vd2mdu 1097 6 might may MD cord-014597-66vd2mdu 1097 7 be be VB cord-014597-66vd2mdu 1097 8 achieved achieve VBN cord-014597-66vd2mdu 1097 9 by by IN cord-014597-66vd2mdu 1097 10 adapting adapt VBG cord-014597-66vd2mdu 1097 11 the the DT cord-014597-66vd2mdu 1097 12 protocol protocol NN cord-014597-66vd2mdu 1097 13 , , , cord-014597-66vd2mdu 1097 14 as as IN cord-014597-66vd2mdu 1097 15 the the DT cord-014597-66vd2mdu 1097 16 results result NNS cord-014597-66vd2mdu 1097 17 shown show VBN cord-014597-66vd2mdu 1097 18 are be VBP cord-014597-66vd2mdu 1097 19 based base VBN cord-014597-66vd2mdu 1097 20 on on IN cord-014597-66vd2mdu 1097 21 a a DT cord-014597-66vd2mdu 1097 22 simple simple JJ cord-014597-66vd2mdu 1097 23 precomplexing precomplexing NN cord-014597-66vd2mdu 1097 24 of of IN cord-014597-66vd2mdu 1097 25 DNA DNA NNP cord-014597-66vd2mdu 1097 26 - - HYPH cord-014597-66vd2mdu 1097 27 PEI PEI NNP cord-014597-66vd2mdu 1097 28 . . . cord-014597-66vd2mdu 1098 1 Moreover moreover RB cord-014597-66vd2mdu 1098 2 , , , cord-014597-66vd2mdu 1098 3 product product NN cord-014597-66vd2mdu 1098 4 yields yield NNS cord-014597-66vd2mdu 1098 5 could could MD cord-014597-66vd2mdu 1098 6 potentially potentially RB cord-014597-66vd2mdu 1098 7 be be VB cord-014597-66vd2mdu 1098 8 increased increase VBN cord-014597-66vd2mdu 1098 9 by by IN cord-014597-66vd2mdu 1098 10 using use VBG cord-014597-66vd2mdu 1098 11 feeds feed NNS cord-014597-66vd2mdu 1098 12 , , , cord-014597-66vd2mdu 1098 13 temperature temperature NN cord-014597-66vd2mdu 1098 14 shifts shift NNS cord-014597-66vd2mdu 1098 15 or or CC cord-014597-66vd2mdu 1098 16 commonly commonly RB cord-014597-66vd2mdu 1098 17 used use VBN cord-014597-66vd2mdu 1098 18 enhancers enhancer NNS cord-014597-66vd2mdu 1098 19 ( ( -LRB- cord-014597-66vd2mdu 1098 20 e.g. e.g. RB cord-014597-66vd2mdu 1098 21 valproic valproic JJ cord-014597-66vd2mdu 1098 22 acids acid NNS cord-014597-66vd2mdu 1098 23 ) ) -RRB- cord-014597-66vd2mdu 1098 24 . . . cord-014597-66vd2mdu 1099 1 Scaling scale VBG cord-014597-66vd2mdu 1099 2 of of IN cord-014597-66vd2mdu 1099 3 a a DT cord-014597-66vd2mdu 1099 4 cell cell NN cord-014597-66vd2mdu 1099 5 culture culture NN cord-014597-66vd2mdu 1099 6 process process NN cord-014597-66vd2mdu 1099 7 is be VBZ cord-014597-66vd2mdu 1099 8 an an DT cord-014597-66vd2mdu 1099 9 essential essential JJ cord-014597-66vd2mdu 1099 10 part part NN cord-014597-66vd2mdu 1099 11 in in IN cord-014597-66vd2mdu 1099 12 its -PRON- PRP$ cord-014597-66vd2mdu 1099 13 development development NN cord-014597-66vd2mdu 1099 14 . . . cord-014597-66vd2mdu 1100 1 In in IN cord-014597-66vd2mdu 1100 2 a a DT cord-014597-66vd2mdu 1100 3 typical typical JJ cord-014597-66vd2mdu 1100 4 approach approach NN cord-014597-66vd2mdu 1100 5 scaling scale VBG cord-014597-66vd2mdu 1100 6 [ [ -LRB- cord-014597-66vd2mdu 1100 7 1 1 CD cord-014597-66vd2mdu 1100 8 ] ] -RRB- cord-014597-66vd2mdu 1100 9 is be VBZ cord-014597-66vd2mdu 1100 10 performed perform VBN cord-014597-66vd2mdu 1100 11 by by IN cord-014597-66vd2mdu 1100 12 keeping keep VBG cord-014597-66vd2mdu 1100 13 a a DT cord-014597-66vd2mdu 1100 14 ( ( -LRB- cord-014597-66vd2mdu 1100 15 critical critical JJ cord-014597-66vd2mdu 1100 16 ) ) -RRB- cord-014597-66vd2mdu 1100 17 process process NN cord-014597-66vd2mdu 1100 18 parameter parameter NN cord-014597-66vd2mdu 1100 19 constant constant JJ cord-014597-66vd2mdu 1100 20 throughout throughout IN cord-014597-66vd2mdu 1100 21 the the DT cord-014597-66vd2mdu 1100 22 complete complete JJ cord-014597-66vd2mdu 1100 23 bioreactor bioreactor NN cord-014597-66vd2mdu 1100 24 range range NN cord-014597-66vd2mdu 1100 25 . . . cord-014597-66vd2mdu 1101 1 This this DT cord-014597-66vd2mdu 1101 2 can can MD cord-014597-66vd2mdu 1101 3 lead lead VB cord-014597-66vd2mdu 1101 4 to to IN cord-014597-66vd2mdu 1101 5 non non JJ cord-014597-66vd2mdu 1101 6 - - JJ cord-014597-66vd2mdu 1101 7 beneficial beneficial JJ cord-014597-66vd2mdu 1101 8 results result NNS cord-014597-66vd2mdu 1101 9 either either CC cord-014597-66vd2mdu 1101 10 on on IN cord-014597-66vd2mdu 1101 11 the the DT cord-014597-66vd2mdu 1101 12 high high JJ cord-014597-66vd2mdu 1101 13 or or CC cord-014597-66vd2mdu 1101 14 the the DT cord-014597-66vd2mdu 1101 15 low low JJ cord-014597-66vd2mdu 1101 16 end end NN cord-014597-66vd2mdu 1101 17 of of IN cord-014597-66vd2mdu 1101 18 the the DT cord-014597-66vd2mdu 1101 19 range range NN cord-014597-66vd2mdu 1101 20 . . . cord-014597-66vd2mdu 1102 1 For for IN cord-014597-66vd2mdu 1102 2 instance instance NN cord-014597-66vd2mdu 1102 3 , , , cord-014597-66vd2mdu 1102 4 the the DT cord-014597-66vd2mdu 1102 5 specific specific JJ cord-014597-66vd2mdu 1102 6 power power NN cord-014597-66vd2mdu 1102 7 input input NN cord-014597-66vd2mdu 1102 8 [ [ -LRB- cord-014597-66vd2mdu 1102 9 P p NN cord-014597-66vd2mdu 1102 10 / / SYM cord-014597-66vd2mdu 1102 11 V v NN cord-014597-66vd2mdu 1102 12 ] ] -RRB- cord-014597-66vd2mdu 1102 13 of of IN cord-014597-66vd2mdu 1102 14 30 30 CD cord-014597-66vd2mdu 1102 15 W W NNP cord-014597-66vd2mdu 1102 16 / / SYM cord-014597-66vd2mdu 1102 17 m m NN cord-014597-66vd2mdu 1102 18 3 3 CD cord-014597-66vd2mdu 1102 19 might may MD cord-014597-66vd2mdu 1102 20 result result VB cord-014597-66vd2mdu 1102 21 in in IN cord-014597-66vd2mdu 1102 22 a a DT cord-014597-66vd2mdu 1102 23 good good JJ cord-014597-66vd2mdu 1102 24 agitation agitation NN cord-014597-66vd2mdu 1102 25 in in IN cord-014597-66vd2mdu 1102 26 production production NN cord-014597-66vd2mdu 1102 27 scale scale NN cord-014597-66vd2mdu 1102 28 whereas whereas IN cord-014597-66vd2mdu 1102 29 it -PRON- PRP cord-014597-66vd2mdu 1102 30 leads lead VBZ cord-014597-66vd2mdu 1102 31 to to IN cord-014597-66vd2mdu 1102 32 a a DT cord-014597-66vd2mdu 1102 33 nonturbulent nonturbulent NN cord-014597-66vd2mdu 1102 34 mixing mix VBG cord-014597-66vd2mdu 1102 35 behavior behavior NN cord-014597-66vd2mdu 1102 36 in in IN cord-014597-66vd2mdu 1102 37 process process NN cord-014597-66vd2mdu 1102 38 development development NN cord-014597-66vd2mdu 1102 39 scale scale NN cord-014597-66vd2mdu 1102 40 . . . cord-014597-66vd2mdu 1103 1 To to TO cord-014597-66vd2mdu 1103 2 overcome overcome VB cord-014597-66vd2mdu 1103 3 this this DT cord-014597-66vd2mdu 1103 4 issue issue NN cord-014597-66vd2mdu 1103 5 a a DT cord-014597-66vd2mdu 1103 6 new new JJ cord-014597-66vd2mdu 1103 7 approach approach NN cord-014597-66vd2mdu 1103 8 for for IN cord-014597-66vd2mdu 1103 9 an an DT cord-014597-66vd2mdu 1103 10 easy easy JJ cord-014597-66vd2mdu 1103 11 scaling scaling NN cord-014597-66vd2mdu 1103 12 procedure procedure NN cord-014597-66vd2mdu 1103 13 was be VBD cord-014597-66vd2mdu 1103 14 developed develop VBN cord-014597-66vd2mdu 1103 15 . . . cord-014597-66vd2mdu 1104 1 This this DT cord-014597-66vd2mdu 1104 2 " " `` cord-014597-66vd2mdu 1104 3 Utility Utility NNP cord-014597-66vd2mdu 1104 4 Function function NN cord-014597-66vd2mdu 1104 5 " " '' cord-014597-66vd2mdu 1104 6 approach approach NN cord-014597-66vd2mdu 1104 7 for for IN cord-014597-66vd2mdu 1104 8 agitation agitation NN cord-014597-66vd2mdu 1104 9 scaling scaling NN cord-014597-66vd2mdu 1104 10 is be VBZ cord-014597-66vd2mdu 1104 11 based base VBN cord-014597-66vd2mdu 1104 12 on on IN cord-014597-66vd2mdu 1104 13 individual individual JJ cord-014597-66vd2mdu 1104 14 functions function NNS cord-014597-66vd2mdu 1104 15 with with IN cord-014597-66vd2mdu 1104 16 a a DT cord-014597-66vd2mdu 1104 17 value value NN cord-014597-66vd2mdu 1104 18 - - HYPH cord-014597-66vd2mdu 1104 19 based base VBN cord-014597-66vd2mdu 1104 20 mapping mapping NN cord-014597-66vd2mdu 1104 21 independent independent JJ cord-014597-66vd2mdu 1104 22 of of IN cord-014597-66vd2mdu 1104 23 bioreactor bioreactor NN cord-014597-66vd2mdu 1104 24 scale scale NN cord-014597-66vd2mdu 1104 25 . . . cord-014597-66vd2mdu 1105 1 Process process VB cord-014597-66vd2mdu 1105 2 insight insight JJ cord-014597-66vd2mdu 1105 3 information information NN cord-014597-66vd2mdu 1105 4 ( ( -LRB- cord-014597-66vd2mdu 1105 5 established establish VBN cord-014597-66vd2mdu 1105 6 either either CC cord-014597-66vd2mdu 1105 7 from from IN cord-014597-66vd2mdu 1105 8 DoE DoE NNP cord-014597-66vd2mdu 1105 9 process process NNP cord-014597-66vd2mdu 1105 10 investigation investigation NN cord-014597-66vd2mdu 1105 11 or or CC cord-014597-66vd2mdu 1105 12 existing existing JJ cord-014597-66vd2mdu 1105 13 experience experience NN cord-014597-66vd2mdu 1105 14 with with IN cord-014597-66vd2mdu 1105 15 a a DT cord-014597-66vd2mdu 1105 16 process process NN cord-014597-66vd2mdu 1105 17 platform platform NN cord-014597-66vd2mdu 1105 18 ) ) -RRB- cord-014597-66vd2mdu 1105 19 is be VBZ cord-014597-66vd2mdu 1105 20 directly directly RB cord-014597-66vd2mdu 1105 21 formalized formalize VBN cord-014597-66vd2mdu 1105 22 into into IN cord-014597-66vd2mdu 1105 23 a a DT cord-014597-66vd2mdu 1105 24 set set NN cord-014597-66vd2mdu 1105 25 of of IN cord-014597-66vd2mdu 1105 26 mappings mapping NNS cord-014597-66vd2mdu 1105 27 which which WDT cord-014597-66vd2mdu 1105 28 transform transform VBP cord-014597-66vd2mdu 1105 29 bioprocess bioprocess NN cord-014597-66vd2mdu 1105 30 values value NNS cord-014597-66vd2mdu 1105 31 into into IN cord-014597-66vd2mdu 1105 32 perceived perceive VBN cord-014597-66vd2mdu 1105 33 benefits benefit NNS cord-014597-66vd2mdu 1105 34 ( ( -LRB- cord-014597-66vd2mdu 1105 35 0 0 CD cord-014597-66vd2mdu 1105 36 to to IN cord-014597-66vd2mdu 1105 37 1 1 CD cord-014597-66vd2mdu 1105 38 ) ) -RRB- cord-014597-66vd2mdu 1105 39 . . . cord-014597-66vd2mdu 1106 1 At at IN cord-014597-66vd2mdu 1106 2 each each DT cord-014597-66vd2mdu 1106 3 bioreactor bioreactor NN cord-014597-66vd2mdu 1106 4 scale scale NN cord-014597-66vd2mdu 1106 5 , , , cord-014597-66vd2mdu 1106 6 parameters parameter NNS cord-014597-66vd2mdu 1106 7 ( ( -LRB- cord-014597-66vd2mdu 1106 8 e.g. e.g. RB cord-014597-66vd2mdu 1106 9 stirring stir VBG cord-014597-66vd2mdu 1106 10 and and CC cord-014597-66vd2mdu 1106 11 gassing gassing NN cord-014597-66vd2mdu 1106 12 ) ) -RRB- cord-014597-66vd2mdu 1106 13 are be VBP cord-014597-66vd2mdu 1106 14 then then RB cord-014597-66vd2mdu 1106 15 chosen choose VBN cord-014597-66vd2mdu 1106 16 to to TO cord-014597-66vd2mdu 1106 17 maximize maximize VB cord-014597-66vd2mdu 1106 18 the the DT cord-014597-66vd2mdu 1106 19 product product NN cord-014597-66vd2mdu 1106 20 of of IN cord-014597-66vd2mdu 1106 21 resultant resultant JJ cord-014597-66vd2mdu 1106 22 Utility Utility NNP cord-014597-66vd2mdu 1106 23 Functions function NNS cord-014597-66vd2mdu 1106 24 . . . cord-014597-66vd2mdu 1107 1 The the DT cord-014597-66vd2mdu 1107 2 model model NN cord-014597-66vd2mdu 1107 3 CHO CHO NNP cord-014597-66vd2mdu 1107 4 fed fed NNP cord-014597-66vd2mdu 1107 5 - - HYPH cord-014597-66vd2mdu 1107 6 batch batch NN cord-014597-66vd2mdu 1107 7 process process NN cord-014597-66vd2mdu 1107 8 in in IN cord-014597-66vd2mdu 1107 9 this this DT cord-014597-66vd2mdu 1107 10 trial trial NN cord-014597-66vd2mdu 1107 11 comprised comprise VBD cord-014597-66vd2mdu 1107 12 a a DT cord-014597-66vd2mdu 1107 13 CHO CHO NNP cord-014597-66vd2mdu 1107 14 DG44 DG44 NNP cord-014597-66vd2mdu 1107 15 cell cell NN cord-014597-66vd2mdu 1107 16 line line NN cord-014597-66vd2mdu 1107 17 that that WDT cord-014597-66vd2mdu 1107 18 was be VBD cord-014597-66vd2mdu 1107 19 transfected transfecte VBN cord-014597-66vd2mdu 1107 20 to to TO cord-014597-66vd2mdu 1107 21 produce produce VB cord-014597-66vd2mdu 1107 22 a a DT cord-014597-66vd2mdu 1107 23 humanized humanize VBN cord-014597-66vd2mdu 1107 24 antibody antibody NN cord-014597-66vd2mdu 1107 25 IgG1 igg1 NN cord-014597-66vd2mdu 1107 26 . . . cord-014597-66vd2mdu 1108 1 A a DT cord-014597-66vd2mdu 1108 2 chemically chemically RB cord-014597-66vd2mdu 1108 3 defined define VBN cord-014597-66vd2mdu 1108 4 media medium NNS cord-014597-66vd2mdu 1108 5 system system NN cord-014597-66vd2mdu 1108 6 was be VBD cord-014597-66vd2mdu 1108 7 used use VBN cord-014597-66vd2mdu 1108 8 . . . cord-014597-66vd2mdu 1109 1 The the DT cord-014597-66vd2mdu 1109 2 process process NN cord-014597-66vd2mdu 1109 3 , , , cord-014597-66vd2mdu 1109 4 including include VBG cord-014597-66vd2mdu 1109 5 cell cell NN cord-014597-66vd2mdu 1109 6 line line NN cord-014597-66vd2mdu 1109 7 , , , cord-014597-66vd2mdu 1109 8 medium medium NN cord-014597-66vd2mdu 1109 9 and and CC cord-014597-66vd2mdu 1109 10 feeding feeding NN cord-014597-66vd2mdu 1109 11 strategy strategy NN cord-014597-66vd2mdu 1109 12 was be VBD cord-014597-66vd2mdu 1109 13 designed design VBN cord-014597-66vd2mdu 1109 14 and and CC cord-014597-66vd2mdu 1109 15 developed develop VBN cord-014597-66vd2mdu 1109 16 by by IN cord-014597-66vd2mdu 1109 17 Sartorius Sartorius NNP cord-014597-66vd2mdu 1109 18 Stedim Stedim NNP cord-014597-66vd2mdu 1109 19 Cellca Cellca NNP cord-014597-66vd2mdu 1109 20 . . . cord-014597-66vd2mdu 1110 1 The the DT cord-014597-66vd2mdu 1110 2 aim aim NN cord-014597-66vd2mdu 1110 3 of of IN cord-014597-66vd2mdu 1110 4 the the DT cord-014597-66vd2mdu 1110 5 gassing gassing NN cord-014597-66vd2mdu 1110 6 scale scale NN cord-014597-66vd2mdu 1110 7 - - HYPH cord-014597-66vd2mdu 1110 8 up up NN cord-014597-66vd2mdu 1110 9 was be VBD cord-014597-66vd2mdu 1110 10 to to TO cord-014597-66vd2mdu 1110 11 achieve achieve VB cord-014597-66vd2mdu 1110 12 similar similar JJ cord-014597-66vd2mdu 1110 13 cell cell NN cord-014597-66vd2mdu 1110 14 densities density NNS cord-014597-66vd2mdu 1110 15 when when WRB cord-014597-66vd2mdu 1110 16 the the DT cord-014597-66vd2mdu 1110 17 addition addition NN cord-014597-66vd2mdu 1110 18 of of IN cord-014597-66vd2mdu 1110 19 pure pure JJ cord-014597-66vd2mdu 1110 20 oxygen oxygen NN cord-014597-66vd2mdu 1110 21 starts start NNS cord-014597-66vd2mdu 1110 22 . . . cord-014597-66vd2mdu 1111 1 For for IN cord-014597-66vd2mdu 1111 2 all all DT cord-014597-66vd2mdu 1111 3 Flexsafe Flexsafe NNP cord-014597-66vd2mdu 1111 4 STR STR NNP cord-014597-66vd2mdu 1111 5 ® ® NN cord-014597-66vd2mdu 1111 6 bags bag NNS cord-014597-66vd2mdu 1111 7 oxygen oxygen NN cord-014597-66vd2mdu 1111 8 was be VBD cord-014597-66vd2mdu 1111 9 sparged sparge VBN cord-014597-66vd2mdu 1111 10 via via IN cord-014597-66vd2mdu 1111 11 the the DT cord-014597-66vd2mdu 1111 12 micro micro NNP cord-014597-66vd2mdu 1111 13 sparger sparger NNP cord-014597-66vd2mdu 1111 14 part part NN cord-014597-66vd2mdu 1111 15 of of IN cord-014597-66vd2mdu 1111 16 the the DT cord-014597-66vd2mdu 1111 17 combi combi NN cord-014597-66vd2mdu 1111 18 sparger sparger NN cord-014597-66vd2mdu 1111 19 . . . cord-014597-66vd2mdu 1112 1 All all DT cord-014597-66vd2mdu 1112 2 other other JJ cord-014597-66vd2mdu 1112 3 systems system NNS cord-014597-66vd2mdu 1112 4 used use VBD cord-014597-66vd2mdu 1112 5 a a DT cord-014597-66vd2mdu 1112 6 ring ring NN cord-014597-66vd2mdu 1112 7 sparger sparger NN cord-014597-66vd2mdu 1112 8 with with IN cord-014597-66vd2mdu 1112 9 holes hole NNS cord-014597-66vd2mdu 1112 10 face face VBP cord-014597-66vd2mdu 1112 11 up up RP cord-014597-66vd2mdu 1112 12 . . . cord-014597-66vd2mdu 1113 1 The the DT cord-014597-66vd2mdu 1113 2 initial initial JJ cord-014597-66vd2mdu 1113 3 air air NN cord-014597-66vd2mdu 1113 4 flow flow NN cord-014597-66vd2mdu 1113 5 rate rate NN cord-014597-66vd2mdu 1113 6 was be VBD cord-014597-66vd2mdu 1113 7 set set VBN cord-014597-66vd2mdu 1113 8 to to IN cord-014597-66vd2mdu 1113 9 an an DT cord-014597-66vd2mdu 1113 10 oxygen oxygen NN cord-014597-66vd2mdu 1113 11 transfer transfer NN cord-014597-66vd2mdu 1113 12 rate rate NN cord-014597-66vd2mdu 1113 13 ( ( -LRB- cord-014597-66vd2mdu 1113 14 k k NNP cord-014597-66vd2mdu 1113 15 L L NNP cord-014597-66vd2mdu 1113 16 a a NNP cord-014597-66vd2mdu 1113 17 ) ) -RRB- cord-014597-66vd2mdu 1113 18 of of IN cord-014597-66vd2mdu 1113 19 8 8 CD cord-014597-66vd2mdu 1113 20 1 1 CD cord-014597-66vd2mdu 1113 21 / / SYM cord-014597-66vd2mdu 1113 22 h h NN cord-014597-66vd2mdu 1113 23 at at IN cord-014597-66vd2mdu 1113 24 the the DT cord-014597-66vd2mdu 1113 25 corresponding corresponding JJ cord-014597-66vd2mdu 1113 26 agitation agitation NN cord-014597-66vd2mdu 1113 27 rate rate NN cord-014597-66vd2mdu 1113 28 and and CC cord-014597-66vd2mdu 1113 29 volume volume NN cord-014597-66vd2mdu 1113 30 . . . cord-014597-66vd2mdu 1114 1 All all DT cord-014597-66vd2mdu 1114 2 process process NN cord-014597-66vd2mdu 1114 3 engineering engineering NN cord-014597-66vd2mdu 1114 4 characterization characterization NN cord-014597-66vd2mdu 1114 5 parameters parameter NNS cord-014597-66vd2mdu 1114 6 were be VBD cord-014597-66vd2mdu 1114 7 determined determine VBN cord-014597-66vd2mdu 1114 8 according accord VBG cord-014597-66vd2mdu 1114 9 to to IN cord-014597-66vd2mdu 1114 10 DECHEMA DECHEMA NNP cord-014597-66vd2mdu 1114 11 guidelines guideline NNS cord-014597-66vd2mdu 1114 12 [ [ -LRB- cord-014597-66vd2mdu 1114 13 2 2 CD cord-014597-66vd2mdu 1114 14 ] ] -RRB- cord-014597-66vd2mdu 1114 15 . . . cord-014597-66vd2mdu 1115 1 With with IN cord-014597-66vd2mdu 1115 2 the the DT cord-014597-66vd2mdu 1115 3 use use NN cord-014597-66vd2mdu 1115 4 of of IN cord-014597-66vd2mdu 1115 5 the the DT cord-014597-66vd2mdu 1115 6 Utility Utility NNP cord-014597-66vd2mdu 1115 7 Functions function NNS cord-014597-66vd2mdu 1115 8 the the DT cord-014597-66vd2mdu 1115 9 discrete discrete JJ cord-014597-66vd2mdu 1115 10 agitation agitation NN cord-014597-66vd2mdu 1115 11 rate rate NN cord-014597-66vd2mdu 1115 12 was be VBD cord-014597-66vd2mdu 1115 13 determined determine VBN cord-014597-66vd2mdu 1115 14 ( ( -LRB- cord-014597-66vd2mdu 1115 15 Table table NN cord-014597-66vd2mdu 1115 16 1 1 CD cord-014597-66vd2mdu 1115 17 ) ) -RRB- cord-014597-66vd2mdu 1115 18 . . . cord-014597-66vd2mdu 1116 1 The the DT cord-014597-66vd2mdu 1116 2 Utility Utility NNP cord-014597-66vd2mdu 1116 3 Functions Functions NNPS cord-014597-66vd2mdu 1116 4 led lead VBD cord-014597-66vd2mdu 1116 5 to to IN cord-014597-66vd2mdu 1116 6 discrete discrete JJ cord-014597-66vd2mdu 1116 7 agitation agitation NN cord-014597-66vd2mdu 1116 8 rates rate NNS cord-014597-66vd2mdu 1116 9 where where WRB cord-014597-66vd2mdu 1116 10 not not RB cord-014597-66vd2mdu 1116 11 only only RB cord-014597-66vd2mdu 1116 12 homogeneous homogeneous JJ cord-014597-66vd2mdu 1116 13 mixing mixing NN cord-014597-66vd2mdu 1116 14 but but CC cord-014597-66vd2mdu 1116 15 also also RB cord-014597-66vd2mdu 1116 16 a a DT cord-014597-66vd2mdu 1116 17 turbulent turbulent JJ cord-014597-66vd2mdu 1116 18 flow flow NN cord-014597-66vd2mdu 1116 19 pattern pattern NN cord-014597-66vd2mdu 1116 20 and and CC cord-014597-66vd2mdu 1116 21 a a DT cord-014597-66vd2mdu 1116 22 suitable suitable JJ cord-014597-66vd2mdu 1116 23 specific specific JJ cord-014597-66vd2mdu 1116 24 power power NN cord-014597-66vd2mdu 1116 25 input input NN cord-014597-66vd2mdu 1116 26 was be VBD cord-014597-66vd2mdu 1116 27 guaranteed guarantee VBN cord-014597-66vd2mdu 1116 28 . . . cord-014597-66vd2mdu 1117 1 The the DT cord-014597-66vd2mdu 1117 2 initial initial JJ cord-014597-66vd2mdu 1117 3 gassing gassing NN cord-014597-66vd2mdu 1117 4 rate rate NN cord-014597-66vd2mdu 1117 5 of of IN cord-014597-66vd2mdu 1117 6 air air NN cord-014597-66vd2mdu 1117 7 supplied supply VBN cord-014597-66vd2mdu 1117 8 enough enough JJ cord-014597-66vd2mdu 1117 9 oxygen oxygen NN cord-014597-66vd2mdu 1117 10 for for IN cord-014597-66vd2mdu 1117 11 5 5 CD cord-014597-66vd2mdu 1117 12 x x SYM cord-014597-66vd2mdu 1117 13 10 10 CD cord-014597-66vd2mdu 1117 14 6 6 CD cord-014597-66vd2mdu 1117 15 cells cell NNS cord-014597-66vd2mdu 1117 16 / / SYM cord-014597-66vd2mdu 1117 17 mL ml NN cord-014597-66vd2mdu 1117 18 in in IN cord-014597-66vd2mdu 1117 19 all all DT cord-014597-66vd2mdu 1117 20 bioreactors bioreactor NNS cord-014597-66vd2mdu 1117 21 . . . cord-014597-66vd2mdu 1118 1 Due due IN cord-014597-66vd2mdu 1118 2 to to IN cord-014597-66vd2mdu 1118 3 the the DT cord-014597-66vd2mdu 1118 4 used use VBN cord-014597-66vd2mdu 1118 5 scaling scaling NN cord-014597-66vd2mdu 1118 6 methods method NNS cord-014597-66vd2mdu 1118 7 the the DT cord-014597-66vd2mdu 1118 8 growth growth NN cord-014597-66vd2mdu 1118 9 patterns pattern NNS cord-014597-66vd2mdu 1118 10 in in IN cord-014597-66vd2mdu 1118 11 all all DT cord-014597-66vd2mdu 1118 12 bioreactor bioreactor NN cord-014597-66vd2mdu 1118 13 scales scale NNS cord-014597-66vd2mdu 1118 14 were be VBD cord-014597-66vd2mdu 1118 15 comparable comparable JJ cord-014597-66vd2mdu 1118 16 . . . cord-014597-66vd2mdu 1119 1 Peak peak JJ cord-014597-66vd2mdu 1119 2 viable viable JJ cord-014597-66vd2mdu 1119 3 cell cell NN cord-014597-66vd2mdu 1119 4 densities density NNS cord-014597-66vd2mdu 1119 5 ( ( -LRB- cord-014597-66vd2mdu 1119 6 VCD VCD NNP cord-014597-66vd2mdu 1119 7 ) ) -RRB- cord-014597-66vd2mdu 1119 8 of of IN cord-014597-66vd2mdu 1119 9 20 20 CD cord-014597-66vd2mdu 1119 10 -26 -26 CD cord-014597-66vd2mdu 1119 11 x x SYM cord-014597-66vd2mdu 1119 12 10 10 CD cord-014597-66vd2mdu 1119 13 6 6 CD cord-014597-66vd2mdu 1119 14 cells cell NNS cord-014597-66vd2mdu 1119 15 / / SYM cord-014597-66vd2mdu 1119 16 mL mL NNS cord-014597-66vd2mdu 1119 17 were be VBD cord-014597-66vd2mdu 1119 18 achieved achieve VBN cord-014597-66vd2mdu 1119 19 and and CC cord-014597-66vd2mdu 1119 20 viability viability NN cord-014597-66vd2mdu 1119 21 at at IN cord-014597-66vd2mdu 1119 22 the the DT cord-014597-66vd2mdu 1119 23 point point NN cord-014597-66vd2mdu 1119 24 of of IN cord-014597-66vd2mdu 1119 25 harvest harvest NN cord-014597-66vd2mdu 1119 26 was be VBD cord-014597-66vd2mdu 1119 27 above above IN cord-014597-66vd2mdu 1119 28 80 80 CD cord-014597-66vd2mdu 1119 29 % % NN cord-014597-66vd2mdu 1119 30 in in IN cord-014597-66vd2mdu 1119 31 all all DT cord-014597-66vd2mdu 1119 32 scales scale NNS cord-014597-66vd2mdu 1119 33 . . . cord-014597-66vd2mdu 1120 1 The the DT cord-014597-66vd2mdu 1120 2 final final JJ cord-014597-66vd2mdu 1120 3 product product NN cord-014597-66vd2mdu 1120 4 concentration concentration NN cord-014597-66vd2mdu 1120 5 was be VBD cord-014597-66vd2mdu 1120 6 in in IN cord-014597-66vd2mdu 1120 7 an an DT cord-014597-66vd2mdu 1120 8 acceptable acceptable JJ cord-014597-66vd2mdu 1120 9 range range NN cord-014597-66vd2mdu 1120 10 of of IN cord-014597-66vd2mdu 1120 11 2.9 2.9 CD cord-014597-66vd2mdu 1120 12 -3.6 -3.6 NNP cord-014597-66vd2mdu 1120 13 g g NNP cord-014597-66vd2mdu 1120 14 / / SYM cord-014597-66vd2mdu 1120 15 L. L. NNP cord-014597-66vd2mdu 1120 16 Product Product NNP cord-014597-66vd2mdu 1120 17 quality quality NN cord-014597-66vd2mdu 1120 18 attributes attribute VBZ cord-014597-66vd2mdu 1120 19 show show VBP cord-014597-66vd2mdu 1120 20 comparability comparability NN cord-014597-66vd2mdu 1120 21 over over IN cord-014597-66vd2mdu 1120 22 the the DT cord-014597-66vd2mdu 1120 23 complete complete JJ cord-014597-66vd2mdu 1120 24 bioreactor bioreactor NN cord-014597-66vd2mdu 1120 25 range range NN cord-014597-66vd2mdu 1120 26 ( ( -LRB- cord-014597-66vd2mdu 1120 27 Fig fig NN cord-014597-66vd2mdu 1120 28 . . . cord-014597-66vd2mdu 1120 29 1 1 CD cord-014597-66vd2mdu 1120 30 ) ) -RRB- cord-014597-66vd2mdu 1120 31 . . . cord-014597-66vd2mdu 1121 1 The the DT cord-014597-66vd2mdu 1121 2 harvest harvest NN cord-014597-66vd2mdu 1121 3 criteria criterion NNS cord-014597-66vd2mdu 1121 4 of of IN cord-014597-66vd2mdu 1121 5 12 12 CD cord-014597-66vd2mdu 1121 6 days day NNS cord-014597-66vd2mdu 1121 7 gave give VBD cord-014597-66vd2mdu 1121 8 a a DT cord-014597-66vd2mdu 1121 9 combination combination NN cord-014597-66vd2mdu 1121 10 of of IN cord-014597-66vd2mdu 1121 11 viability viability NN cord-014597-66vd2mdu 1121 12 and and CC cord-014597-66vd2mdu 1121 13 product product NN cord-014597-66vd2mdu 1121 14 concentration concentration NN cord-014597-66vd2mdu 1121 15 that that WDT cord-014597-66vd2mdu 1121 16 made make VBD cord-014597-66vd2mdu 1121 17 it -PRON- PRP cord-014597-66vd2mdu 1121 18 easy easy JJ cord-014597-66vd2mdu 1121 19 to to TO cord-014597-66vd2mdu 1121 20 process process VB cord-014597-66vd2mdu 1121 21 the the DT cord-014597-66vd2mdu 1121 22 cell cell NN cord-014597-66vd2mdu 1121 23 broth broth NN cord-014597-66vd2mdu 1121 24 during during IN cord-014597-66vd2mdu 1121 25 cell cell NN cord-014597-66vd2mdu 1121 26 removal removal NN cord-014597-66vd2mdu 1121 27 and and CC cord-014597-66vd2mdu 1121 28 other other JJ cord-014597-66vd2mdu 1121 29 downstream downstream JJ cord-014597-66vd2mdu 1121 30 steps step NNS cord-014597-66vd2mdu 1121 31 . . . cord-014597-66vd2mdu 1122 1 The the DT cord-014597-66vd2mdu 1122 2 process process NN cord-014597-66vd2mdu 1122 3 implementation implementation NN cord-014597-66vd2mdu 1122 4 of of IN cord-014597-66vd2mdu 1122 5 the the DT cord-014597-66vd2mdu 1122 6 CHO CHO NNP cord-014597-66vd2mdu 1122 7 production production NN cord-014597-66vd2mdu 1122 8 System system NN cord-014597-66vd2mdu 1122 9 -Expressing -Expressing NNP cord-014597-66vd2mdu 1122 10 mAb mab NN cord-014597-66vd2mdu 1122 11 2 2 CD cord-014597-66vd2mdu 1122 12 was be VBD cord-014597-66vd2mdu 1122 13 successfully successfully RB cord-014597-66vd2mdu 1122 14 performed perform VBN cord-014597-66vd2mdu 1122 15 with with IN cord-014597-66vd2mdu 1122 16 the the DT cord-014597-66vd2mdu 1122 17 use use NN cord-014597-66vd2mdu 1122 18 of of IN cord-014597-66vd2mdu 1122 19 Utility Utility NNP cord-014597-66vd2mdu 1122 20 Functions Functions NNPS cord-014597-66vd2mdu 1122 21 . . . cord-014597-66vd2mdu 1123 1 Cell cell NN cord-014597-66vd2mdu 1123 2 growth growth NN cord-014597-66vd2mdu 1123 3 , , , cord-014597-66vd2mdu 1123 4 productivity productivity NN cord-014597-66vd2mdu 1123 5 and and CC cord-014597-66vd2mdu 1123 6 product product NN cord-014597-66vd2mdu 1123 7 quality quality NN cord-014597-66vd2mdu 1123 8 is be VBZ cord-014597-66vd2mdu 1123 9 comparable comparable JJ cord-014597-66vd2mdu 1123 10 over over IN cord-014597-66vd2mdu 1123 11 the the DT cord-014597-66vd2mdu 1123 12 complete complete JJ cord-014597-66vd2mdu 1123 13 bioreactor bioreactor NN cord-014597-66vd2mdu 1123 14 range range NN cord-014597-66vd2mdu 1123 15 . . . cord-014597-66vd2mdu 1124 1 Background Background NNP cord-014597-66vd2mdu 1124 2 Endoplasmic Endoplasmic NNP cord-014597-66vd2mdu 1124 3 reticulum reticulum NN cord-014597-66vd2mdu 1124 4 ( ( -LRB- cord-014597-66vd2mdu 1124 5 ER ER NNP cord-014597-66vd2mdu 1124 6 ) ) -RRB- cord-014597-66vd2mdu 1124 7 , , , cord-014597-66vd2mdu 1124 8 the the DT cord-014597-66vd2mdu 1124 9 central central JJ cord-014597-66vd2mdu 1124 10 part part NN cord-014597-66vd2mdu 1124 11 of of IN cord-014597-66vd2mdu 1124 12 the the DT cord-014597-66vd2mdu 1124 13 secretory secretory JJ cord-014597-66vd2mdu 1124 14 pathways pathway NNS cord-014597-66vd2mdu 1124 15 in in IN cord-014597-66vd2mdu 1124 16 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 1124 17 cells cell NNS cord-014597-66vd2mdu 1124 18 , , , cord-014597-66vd2mdu 1124 19 is be VBZ cord-014597-66vd2mdu 1124 20 responsible responsible JJ cord-014597-66vd2mdu 1124 21 for for IN cord-014597-66vd2mdu 1124 22 controlling control VBG cord-014597-66vd2mdu 1124 23 the the DT cord-014597-66vd2mdu 1124 24 quality quality NN cord-014597-66vd2mdu 1124 25 of of IN cord-014597-66vd2mdu 1124 26 secreted secrete VBN cord-014597-66vd2mdu 1124 27 and and CC cord-014597-66vd2mdu 1124 28 resident resident NN cord-014597-66vd2mdu 1124 29 proteins protein NNS cord-014597-66vd2mdu 1124 30 through through IN cord-014597-66vd2mdu 1124 31 the the DT cord-014597-66vd2mdu 1124 32 regulation regulation NN cord-014597-66vd2mdu 1124 33 of of IN cord-014597-66vd2mdu 1124 34 protein protein NN cord-014597-66vd2mdu 1124 35 translocation translocation NN cord-014597-66vd2mdu 1124 36 , , , cord-014597-66vd2mdu 1124 37 protein protein NN cord-014597-66vd2mdu 1124 38 folding folding NN cord-014597-66vd2mdu 1124 39 , , , cord-014597-66vd2mdu 1124 40 and and CC cord-014597-66vd2mdu 1124 41 early early JJ cord-014597-66vd2mdu 1124 42 post post JJ cord-014597-66vd2mdu 1124 43 - - JJ cord-014597-66vd2mdu 1124 44 translational translational JJ cord-014597-66vd2mdu 1124 45 modifications modification NNS cord-014597-66vd2mdu 1124 46 [ [ -LRB- cord-014597-66vd2mdu 1124 47 1 1 CD cord-014597-66vd2mdu 1124 48 ] ] -RRB- cord-014597-66vd2mdu 1124 49 . . . cord-014597-66vd2mdu 1125 1 A a DT cord-014597-66vd2mdu 1125 2 number number NN cord-014597-66vd2mdu 1125 3 of of IN cord-014597-66vd2mdu 1125 4 physiological physiological JJ cord-014597-66vd2mdu 1125 5 conditions condition NNS cord-014597-66vd2mdu 1125 6 such such JJ cord-014597-66vd2mdu 1125 7 as as IN cord-014597-66vd2mdu 1125 8 oxidative oxidative JJ cord-014597-66vd2mdu 1125 9 stress stress NN cord-014597-66vd2mdu 1125 10 , , , cord-014597-66vd2mdu 1125 11 hypoglycemia hypoglycemia NN cord-014597-66vd2mdu 1125 12 , , , cord-014597-66vd2mdu 1125 13 acidosis acidosis NN cord-014597-66vd2mdu 1125 14 , , , cord-014597-66vd2mdu 1125 15 and and CC cord-014597-66vd2mdu 1125 16 thermal thermal JJ cord-014597-66vd2mdu 1125 17 instability instability NN cord-014597-66vd2mdu 1125 18 can can MD cord-014597-66vd2mdu 1125 19 disturb disturb VB cord-014597-66vd2mdu 1125 20 the the DT cord-014597-66vd2mdu 1125 21 ER ER NNP cord-014597-66vd2mdu 1125 22 functions function NNS cord-014597-66vd2mdu 1125 23 , , , cord-014597-66vd2mdu 1125 24 which which WDT cord-014597-66vd2mdu 1125 25 triggers trigger VBZ cord-014597-66vd2mdu 1125 26 ER ER NNP cord-014597-66vd2mdu 1125 27 stress stress NN cord-014597-66vd2mdu 1125 28 [ [ -LRB- cord-014597-66vd2mdu 1125 29 2 2 CD cord-014597-66vd2mdu 1125 30 ] ] -RRB- cord-014597-66vd2mdu 1125 31 . . . cord-014597-66vd2mdu 1126 1 Prolonged prolonged JJ cord-014597-66vd2mdu 1126 2 ER ER NNP cord-014597-66vd2mdu 1126 3 stress stress NN cord-014597-66vd2mdu 1126 4 induces induce VBZ cord-014597-66vd2mdu 1126 5 apoptotic apoptotic JJ cord-014597-66vd2mdu 1126 6 cell cell NN cord-014597-66vd2mdu 1126 7 death death NN cord-014597-66vd2mdu 1126 8 [ [ -LRB- cord-014597-66vd2mdu 1126 9 3 3 CD cord-014597-66vd2mdu 1126 10 ] ] -RRB- cord-014597-66vd2mdu 1126 11 . . . cord-014597-66vd2mdu 1127 1 Oxidative oxidative JJ cord-014597-66vd2mdu 1127 2 stress stress NN cord-014597-66vd2mdu 1127 3 that that WDT cord-014597-66vd2mdu 1127 4 naturally naturally RB cord-014597-66vd2mdu 1127 5 accumulates accumulate VBZ cord-014597-66vd2mdu 1127 6 in in IN cord-014597-66vd2mdu 1127 7 the the DT cord-014597-66vd2mdu 1127 8 ER ER NNP cord-014597-66vd2mdu 1127 9 as as IN cord-014597-66vd2mdu 1127 10 a a DT cord-014597-66vd2mdu 1127 11 result result NN cord-014597-66vd2mdu 1127 12 of of IN cord-014597-66vd2mdu 1127 13 mitochondrial mitochondrial JJ cord-014597-66vd2mdu 1127 14 energy energy NN cord-014597-66vd2mdu 1127 15 metabolism metabolism NN cord-014597-66vd2mdu 1127 16 and and CC cord-014597-66vd2mdu 1127 17 protein protein NN cord-014597-66vd2mdu 1127 18 synthesis synthesis NN cord-014597-66vd2mdu 1127 19 can can MD cord-014597-66vd2mdu 1127 20 disturb disturb VB cord-014597-66vd2mdu 1127 21 the the DT cord-014597-66vd2mdu 1127 22 ER ER NNP cord-014597-66vd2mdu 1127 23 function function NN cord-014597-66vd2mdu 1127 24 [ [ -LRB- cord-014597-66vd2mdu 1127 25 4 4 CD cord-014597-66vd2mdu 1127 26 ] ] -RRB- cord-014597-66vd2mdu 1127 27 . . . cord-014597-66vd2mdu 1128 1 Because because IN cord-014597-66vd2mdu 1128 2 ER ER NNP cord-014597-66vd2mdu 1128 3 has have VBZ cord-014597-66vd2mdu 1128 4 a a DT cord-014597-66vd2mdu 1128 5 responsibility responsibility NN cord-014597-66vd2mdu 1128 6 on on IN cord-014597-66vd2mdu 1128 7 the the DT cord-014597-66vd2mdu 1128 8 protein protein NN cord-014597-66vd2mdu 1128 9 synthesis synthesis NN cord-014597-66vd2mdu 1128 10 and and CC cord-014597-66vd2mdu 1128 11 quality quality NN cord-014597-66vd2mdu 1128 12 control control NN cord-014597-66vd2mdu 1128 13 of of IN cord-014597-66vd2mdu 1128 14 the the DT cord-014597-66vd2mdu 1128 15 secreted secrete VBN cord-014597-66vd2mdu 1128 16 proteins protein NNS cord-014597-66vd2mdu 1128 17 , , , cord-014597-66vd2mdu 1128 18 ER ER NNP cord-014597-66vd2mdu 1128 19 homeostasis homeostasis NN cord-014597-66vd2mdu 1128 20 has have VBZ cord-014597-66vd2mdu 1128 21 to to TO cord-014597-66vd2mdu 1128 22 be be VB cord-014597-66vd2mdu 1128 23 well well RB cord-014597-66vd2mdu 1128 24 maintained maintain VBN cord-014597-66vd2mdu 1128 25 . . . cord-014597-66vd2mdu 1129 1 When when WRB cord-014597-66vd2mdu 1129 2 H h NN cord-014597-66vd2mdu 1129 3 2 2 CD cord-014597-66vd2mdu 1129 4 O o NN cord-014597-66vd2mdu 1129 5 2 2 CD cord-014597-66vd2mdu 1129 6 , , , cord-014597-66vd2mdu 1129 7 an an DT cord-014597-66vd2mdu 1129 8 oxidative oxidative JJ cord-014597-66vd2mdu 1129 9 stress stress NN cord-014597-66vd2mdu 1129 10 inducer inducer NN cord-014597-66vd2mdu 1129 11 , , , cord-014597-66vd2mdu 1129 12 was be VBD cord-014597-66vd2mdu 1129 13 added add VBN cord-014597-66vd2mdu 1129 14 to to IN cord-014597-66vd2mdu 1129 15 recombinant recombinant JJ cord-014597-66vd2mdu 1129 16 Chinese chinese JJ cord-014597-66vd2mdu 1129 17 hamster hamster NN cord-014597-66vd2mdu 1129 18 ovary ovary NN cord-014597-66vd2mdu 1129 19 ( ( -LRB- cord-014597-66vd2mdu 1129 20 rCHO rcho NN cord-014597-66vd2mdu 1129 21 ) ) -RRB- cord-014597-66vd2mdu 1129 22 cell cell NN cord-014597-66vd2mdu 1129 23 cultures culture NNS cord-014597-66vd2mdu 1129 24 , , , cord-014597-66vd2mdu 1129 25 it -PRON- PRP cord-014597-66vd2mdu 1129 26 reduced reduce VBD cord-014597-66vd2mdu 1129 27 cell cell NN cord-014597-66vd2mdu 1129 28 growth growth NN cord-014597-66vd2mdu 1129 29 , , , cord-014597-66vd2mdu 1129 30 monoclonal monoclonal JJ cord-014597-66vd2mdu 1129 31 antibody antibody NN cord-014597-66vd2mdu 1129 32 ( ( -LRB- cord-014597-66vd2mdu 1129 33 mAb mab NN cord-014597-66vd2mdu 1129 34 ) ) -RRB- cord-014597-66vd2mdu 1129 35 production production NN cord-014597-66vd2mdu 1129 36 , , , cord-014597-66vd2mdu 1129 37 and and CC cord-014597-66vd2mdu 1129 38 galactosylated galactosylate VBN cord-014597-66vd2mdu 1129 39 form form NN cord-014597-66vd2mdu 1129 40 of of IN cord-014597-66vd2mdu 1129 41 mAb mab NN cord-014597-66vd2mdu 1129 42 in in IN cord-014597-66vd2mdu 1129 43 a a DT cord-014597-66vd2mdu 1129 44 dose dose NN cord-014597-66vd2mdu 1129 45 - - HYPH cord-014597-66vd2mdu 1129 46 dependent dependent JJ cord-014597-66vd2mdu 1129 47 manner manner NN cord-014597-66vd2mdu 1129 48 . . . cord-014597-66vd2mdu 1130 1 Antioxidants antioxidant NNS cord-014597-66vd2mdu 1130 2 can can MD cord-014597-66vd2mdu 1130 3 reduce reduce VB cord-014597-66vd2mdu 1130 4 the the DT cord-014597-66vd2mdu 1130 5 oxidative oxidative JJ cord-014597-66vd2mdu 1130 6 stress stress NN cord-014597-66vd2mdu 1130 7 level level NN cord-014597-66vd2mdu 1130 8 and and CC cord-014597-66vd2mdu 1130 9 suppress suppress VB cord-014597-66vd2mdu 1130 10 the the DT cord-014597-66vd2mdu 1130 11 apoptotic apoptotic JJ cord-014597-66vd2mdu 1130 12 cell cell NN cord-014597-66vd2mdu 1130 13 death death NN cord-014597-66vd2mdu 1130 14 by by IN cord-014597-66vd2mdu 1130 15 scavenging scavenge VBG cord-014597-66vd2mdu 1130 16 oxygen oxygen NN cord-014597-66vd2mdu 1130 17 free free JJ cord-014597-66vd2mdu 1130 18 radicals radical NNS cord-014597-66vd2mdu 1130 19 , , , cord-014597-66vd2mdu 1130 20 inhibiting inhibit VBG cord-014597-66vd2mdu 1130 21 chain chain NN cord-014597-66vd2mdu 1130 22 reaction reaction NN cord-014597-66vd2mdu 1130 23 of of IN cord-014597-66vd2mdu 1130 24 oxidation oxidation NN cord-014597-66vd2mdu 1130 25 , , , cord-014597-66vd2mdu 1130 26 and and CC cord-014597-66vd2mdu 1130 27 detoxifying detoxify VBG cord-014597-66vd2mdu 1130 28 peroxide peroxide NN cord-014597-66vd2mdu 1130 29 [ [ -LRB- cord-014597-66vd2mdu 1130 30 5 5 CD cord-014597-66vd2mdu 1130 31 ] ] -RRB- cord-014597-66vd2mdu 1130 32 . . . cord-014597-66vd2mdu 1131 1 However however RB cord-014597-66vd2mdu 1131 2 , , , cord-014597-66vd2mdu 1131 3 despite despite IN cord-014597-66vd2mdu 1131 4 the the DT cord-014597-66vd2mdu 1131 5 importance importance NN cord-014597-66vd2mdu 1131 6 of of IN cord-014597-66vd2mdu 1131 7 mass mass NN cord-014597-66vd2mdu 1131 8 production production NN cord-014597-66vd2mdu 1131 9 of of IN cord-014597-66vd2mdu 1131 10 mAbs mAbs NNP cord-014597-66vd2mdu 1131 11 , , , cord-014597-66vd2mdu 1131 12 studies study NNS cord-014597-66vd2mdu 1131 13 on on IN cord-014597-66vd2mdu 1131 14 the the DT cord-014597-66vd2mdu 1131 15 effect effect NN cord-014597-66vd2mdu 1131 16 of of IN cord-014597-66vd2mdu 1131 17 antioxidants antioxidant NNS cord-014597-66vd2mdu 1131 18 on on IN cord-014597-66vd2mdu 1131 19 the the DT cord-014597-66vd2mdu 1131 20 production production NN cord-014597-66vd2mdu 1131 21 and and CC cord-014597-66vd2mdu 1131 22 quality quality NN cord-014597-66vd2mdu 1131 23 of of IN cord-014597-66vd2mdu 1131 24 mAbs mabs NN cord-014597-66vd2mdu 1131 25 in in IN cord-014597-66vd2mdu 1131 26 rCHO rcho JJ cord-014597-66vd2mdu 1131 27 cell cell NN cord-014597-66vd2mdu 1131 28 cultures culture NNS cord-014597-66vd2mdu 1131 29 have have VBP cord-014597-66vd2mdu 1131 30 not not RB cord-014597-66vd2mdu 1131 31 been be VBN cord-014597-66vd2mdu 1131 32 fully fully RB cord-014597-66vd2mdu 1131 33 substantiated substantiate VBN cord-014597-66vd2mdu 1131 34 . . . cord-014597-66vd2mdu 1132 1 To to TO cord-014597-66vd2mdu 1132 2 find find VB cord-014597-66vd2mdu 1132 3 a a DT cord-014597-66vd2mdu 1132 4 more more RBR cord-014597-66vd2mdu 1132 5 effective effective JJ cord-014597-66vd2mdu 1132 6 antioxidant antioxidant NN cord-014597-66vd2mdu 1132 7 in in IN cord-014597-66vd2mdu 1132 8 rCHO rcho JJ cord-014597-66vd2mdu 1132 9 cell cell NN cord-014597-66vd2mdu 1132 10 cultures culture NNS cord-014597-66vd2mdu 1132 11 , , , cord-014597-66vd2mdu 1132 12 six six CD cord-014597-66vd2mdu 1132 13 different different JJ cord-014597-66vd2mdu 1132 14 antioxidants antioxidant NNS cord-014597-66vd2mdu 1132 15 including include VBG cord-014597-66vd2mdu 1132 16 baicalein baicalein NNP cord-014597-66vd2mdu 1132 17 , , , cord-014597-66vd2mdu 1132 18 which which WDT cord-014597-66vd2mdu 1132 19 have have VBP cord-014597-66vd2mdu 1132 20 used use VBN cord-014597-66vd2mdu 1132 21 widely widely RB cord-014597-66vd2mdu 1132 22 in in IN cord-014597-66vd2mdu 1132 23 mammalian mammalian JJ cord-014597-66vd2mdu 1132 24 cell cell NN cord-014597-66vd2mdu 1132 25 cultures culture NNS cord-014597-66vd2mdu 1132 26 , , , cord-014597-66vd2mdu 1132 27 were be VBD cord-014597-66vd2mdu 1132 28 evaluated evaluate VBN cord-014597-66vd2mdu 1132 29 as as IN cord-014597-66vd2mdu 1132 30 chemical chemical JJ cord-014597-66vd2mdu 1132 31 supplements supplement NNS cord-014597-66vd2mdu 1132 32 with with IN cord-014597-66vd2mdu 1132 33 two two CD cord-014597-66vd2mdu 1132 34 different different JJ cord-014597-66vd2mdu 1132 35 rCHO rcho NN cord-014597-66vd2mdu 1132 36 cell cell NN cord-014597-66vd2mdu 1132 37 lines line NNS cord-014597-66vd2mdu 1132 38 producing produce VBG cord-014597-66vd2mdu 1132 39 the the DT cord-014597-66vd2mdu 1132 40 same same JJ cord-014597-66vd2mdu 1132 41 mAb mAb NNS cord-014597-66vd2mdu 1132 42 in in IN cord-014597-66vd2mdu 1132 43 6-well 6-well CD cord-014597-66vd2mdu 1132 44 plates plate NNS cord-014597-66vd2mdu 1132 45 . . . cord-014597-66vd2mdu 1133 1 Then then RB cord-014597-66vd2mdu 1133 2 , , , cord-014597-66vd2mdu 1133 3 batch batch NN cord-014597-66vd2mdu 1133 4 and and CC cord-014597-66vd2mdu 1133 5 fed fed JJ cord-014597-66vd2mdu 1133 6 - - HYPH cord-014597-66vd2mdu 1133 7 batch batch NN cord-014597-66vd2mdu 1133 8 cultures culture NNS cord-014597-66vd2mdu 1133 9 were be VBD cord-014597-66vd2mdu 1133 10 performed perform VBN cord-014597-66vd2mdu 1133 11 in in IN cord-014597-66vd2mdu 1133 12 shake shake NN cord-014597-66vd2mdu 1133 13 flasks flask NNS cord-014597-66vd2mdu 1133 14 with with IN cord-014597-66vd2mdu 1133 15 the the DT cord-014597-66vd2mdu 1133 16 supplementation supplementation NN cord-014597-66vd2mdu 1133 17 of of IN cord-014597-66vd2mdu 1133 18 baicalein baicalein NNP cord-014597-66vd2mdu 1133 19 , , , cord-014597-66vd2mdu 1133 20 which which WDT cord-014597-66vd2mdu 1133 21 showed show VBD cord-014597-66vd2mdu 1133 22 the the DT cord-014597-66vd2mdu 1133 23 best good JJS cord-014597-66vd2mdu 1133 24 effect effect NN cord-014597-66vd2mdu 1133 25 on on IN cord-014597-66vd2mdu 1133 26 culture culture NN cord-014597-66vd2mdu 1133 27 performance performance NN cord-014597-66vd2mdu 1133 28 among among IN cord-014597-66vd2mdu 1133 29 the the DT cord-014597-66vd2mdu 1133 30 6 6 CD cord-014597-66vd2mdu 1133 31 antioxidants antioxidant NNS cord-014597-66vd2mdu 1133 32 . . . cord-014597-66vd2mdu 1134 1 The the DT cord-014597-66vd2mdu 1134 2 reactive reactive JJ cord-014597-66vd2mdu 1134 3 oxygen oxygen NN cord-014597-66vd2mdu 1134 4 species specie NNS cord-014597-66vd2mdu 1134 5 ( ( -LRB- cord-014597-66vd2mdu 1134 6 ROS ROS NNP cord-014597-66vd2mdu 1134 7 ) ) -RRB- cord-014597-66vd2mdu 1134 8 and and CC cord-014597-66vd2mdu 1134 9 ER ER NNP cord-014597-66vd2mdu 1134 10 stress stress NN cord-014597-66vd2mdu 1134 11 levels level NNS cord-014597-66vd2mdu 1134 12 were be VBD cord-014597-66vd2mdu 1134 13 measured measure VBN cord-014597-66vd2mdu 1134 14 to to TO cord-014597-66vd2mdu 1134 15 study study VB cord-014597-66vd2mdu 1134 16 the the DT cord-014597-66vd2mdu 1134 17 effect effect NN cord-014597-66vd2mdu 1134 18 of of IN cord-014597-66vd2mdu 1134 19 baicalein baicalein NNP cord-014597-66vd2mdu 1134 20 on on IN cord-014597-66vd2mdu 1134 21 mAb mab NN cord-014597-66vd2mdu 1134 22 production production NN cord-014597-66vd2mdu 1134 23 and and CC cord-014597-66vd2mdu 1134 24 quality quality NN cord-014597-66vd2mdu 1134 25 . . . cord-014597-66vd2mdu 1135 1 Among among IN cord-014597-66vd2mdu 1135 2 these these DT cord-014597-66vd2mdu 1135 3 antioxidants antioxidant NNS cord-014597-66vd2mdu 1135 4 , , , cord-014597-66vd2mdu 1135 5 baicalein baicalein NNP cord-014597-66vd2mdu 1135 6 showed show VBD cord-014597-66vd2mdu 1135 7 the the DT cord-014597-66vd2mdu 1135 8 best good JJS cord-014597-66vd2mdu 1135 9 mAb mab NN cord-014597-66vd2mdu 1135 10 production production NN cord-014597-66vd2mdu 1135 11 performance performance NN cord-014597-66vd2mdu 1135 12 . . . cord-014597-66vd2mdu 1136 1 Addition addition NN cord-014597-66vd2mdu 1136 2 of of IN cord-014597-66vd2mdu 1136 3 baicalein baicalein NNP cord-014597-66vd2mdu 1136 4 significantly significantly RB cord-014597-66vd2mdu 1136 5 reduced reduce VBD cord-014597-66vd2mdu 1136 6 the the DT cord-014597-66vd2mdu 1136 7 expression expression NN cord-014597-66vd2mdu 1136 8 level level NN cord-014597-66vd2mdu 1136 9 of of IN cord-014597-66vd2mdu 1136 10 BiP bip NN cord-014597-66vd2mdu 1136 11 and and CC cord-014597-66vd2mdu 1136 12 CHOP chop VB cord-014597-66vd2mdu 1136 13 along along RP cord-014597-66vd2mdu 1136 14 with with IN cord-014597-66vd2mdu 1136 15 reduced reduce VBN cord-014597-66vd2mdu 1136 16 ROS ROS NNP cord-014597-66vd2mdu 1136 17 level level NN cord-014597-66vd2mdu 1136 18 , , , cord-014597-66vd2mdu 1136 19 suggesting suggest VBG cord-014597-66vd2mdu 1136 20 oxidative oxidative JJ cord-014597-66vd2mdu 1136 21 stress stress NN cord-014597-66vd2mdu 1136 22 accumulated accumulate VBN cord-014597-66vd2mdu 1136 23 in in IN cord-014597-66vd2mdu 1136 24 the the DT cord-014597-66vd2mdu 1136 25 cells cell NNS cord-014597-66vd2mdu 1136 26 can can MD cord-014597-66vd2mdu 1136 27 be be VB cord-014597-66vd2mdu 1136 28 relieved relieve VBN cord-014597-66vd2mdu 1136 29 using use VBG cord-014597-66vd2mdu 1136 30 baicalein baicalein NNP cord-014597-66vd2mdu 1136 31 . . . cord-014597-66vd2mdu 1137 1 As as IN cord-014597-66vd2mdu 1137 2 a a DT cord-014597-66vd2mdu 1137 3 result result NN cord-014597-66vd2mdu 1137 4 , , , cord-014597-66vd2mdu 1137 5 addition addition NN cord-014597-66vd2mdu 1137 6 of of IN cord-014597-66vd2mdu 1137 7 baicalein baicalein NNP cord-014597-66vd2mdu 1137 8 in in IN cord-014597-66vd2mdu 1137 9 batch batch NN cord-014597-66vd2mdu 1137 10 cultures culture NNS cord-014597-66vd2mdu 1137 11 resulted result VBD cord-014597-66vd2mdu 1137 12 in in IN cord-014597-66vd2mdu 1137 13 1.7 1.7 CD cord-014597-66vd2mdu 1137 14 -1.8-fold -1.8-fold NN cord-014597-66vd2mdu 1137 15 increase increase NN cord-014597-66vd2mdu 1137 16 in in IN cord-014597-66vd2mdu 1137 17 the the DT cord-014597-66vd2mdu 1137 18 maximum maximum JJ cord-014597-66vd2mdu 1137 19 mAb mab NN cord-014597-66vd2mdu 1137 20 concentration concentration NN cord-014597-66vd2mdu 1137 21 ( ( -LRB- cord-014597-66vd2mdu 1137 22 MMC MMC NNP cord-014597-66vd2mdu 1137 23 ) ) -RRB- cord-014597-66vd2mdu 1137 24 , , , cord-014597-66vd2mdu 1137 25 while while IN cord-014597-66vd2mdu 1137 26 maintaining maintain VBG cord-014597-66vd2mdu 1137 27 the the DT cord-014597-66vd2mdu 1137 28 galactosylation galactosylation NN cord-014597-66vd2mdu 1137 29 of of IN cord-014597-66vd2mdu 1137 30 mAb mAb NNS cord-014597-66vd2mdu 1137 31 ( ( -LRB- cord-014597-66vd2mdu 1137 32 Fig Fig NNP cord-014597-66vd2mdu 1137 33 . . . cord-014597-66vd2mdu 1137 34 1 1 CD cord-014597-66vd2mdu 1137 35 and and CC cord-014597-66vd2mdu 1137 36 Table Table NNP cord-014597-66vd2mdu 1137 37 1 1 CD cord-014597-66vd2mdu 1137 38 ) ) -RRB- cord-014597-66vd2mdu 1137 39 . . . cord-014597-66vd2mdu 1138 1 Likewise likewise RB cord-014597-66vd2mdu 1138 2 , , , cord-014597-66vd2mdu 1138 3 addition addition NN cord-014597-66vd2mdu 1138 4 of of IN cord-014597-66vd2mdu 1138 5 baicalein baicalein NNP cord-014597-66vd2mdu 1138 6 in in IN cord-014597-66vd2mdu 1138 7 fed fed NNP cord-014597-66vd2mdu 1138 8 - - HYPH cord-014597-66vd2mdu 1138 9 batch batch NN cord-014597-66vd2mdu 1138 10 culture culture NN cord-014597-66vd2mdu 1138 11 resulted result VBD cord-014597-66vd2mdu 1138 12 in in IN cord-014597-66vd2mdu 1138 13 1.6-fold 1.6-fold CD cord-014597-66vd2mdu 1138 14 increase increase NN cord-014597-66vd2mdu 1138 15 in in IN cord-014597-66vd2mdu 1138 16 the the DT cord-014597-66vd2mdu 1138 17 MMC mmc NN cord-014597-66vd2mdu 1138 18 while while IN cord-014597-66vd2mdu 1138 19 maintaining maintain VBG cord-014597-66vd2mdu 1138 20 the the DT cord-014597-66vd2mdu 1138 21 galactosylation galactosylation NN cord-014597-66vd2mdu 1138 22 of of IN cord-014597-66vd2mdu 1138 23 mAb mAb NNS cord-014597-66vd2mdu 1138 24 . . . cord-014597-66vd2mdu 1139 1 Oxidative oxidative JJ cord-014597-66vd2mdu 1139 2 stress stress NN cord-014597-66vd2mdu 1139 3 negatively negatively RB cord-014597-66vd2mdu 1139 4 affected affect VBD cord-014597-66vd2mdu 1139 5 the the DT cord-014597-66vd2mdu 1139 6 production production NN cord-014597-66vd2mdu 1139 7 and and CC cord-014597-66vd2mdu 1139 8 galactosylation galactosylation NN cord-014597-66vd2mdu 1139 9 of of IN cord-014597-66vd2mdu 1139 10 mAb mab NN cord-014597-66vd2mdu 1139 11 in in IN cord-014597-66vd2mdu 1139 12 rCHO rcho JJ cord-014597-66vd2mdu 1139 13 cell cell NN cord-014597-66vd2mdu 1139 14 cultures culture NNS cord-014597-66vd2mdu 1139 15 . . . cord-014597-66vd2mdu 1140 1 Among among IN cord-014597-66vd2mdu 1140 2 the the DT cord-014597-66vd2mdu 1140 3 various various JJ cord-014597-66vd2mdu 1140 4 antioxidants antioxidant NNS cord-014597-66vd2mdu 1140 5 tested test VBN cord-014597-66vd2mdu 1140 6 in in IN cord-014597-66vd2mdu 1140 7 this this DT cord-014597-66vd2mdu 1140 8 study study NN cord-014597-66vd2mdu 1140 9 , , , cord-014597-66vd2mdu 1140 10 baicalein baicalein NNP cord-014597-66vd2mdu 1140 11 showed show VBD cord-014597-66vd2mdu 1140 12 the the DT cord-014597-66vd2mdu 1140 13 best good JJS cord-014597-66vd2mdu 1140 14 mAb mab NN cord-014597-66vd2mdu 1140 15 production production NN cord-014597-66vd2mdu 1140 16 performance performance NN cord-014597-66vd2mdu 1140 17 in in IN cord-014597-66vd2mdu 1140 18 both both DT cord-014597-66vd2mdu 1140 19 batch batch NN cord-014597-66vd2mdu 1140 20 and and CC cord-014597-66vd2mdu 1140 21 fed fed JJ cord-014597-66vd2mdu 1140 22 - - HYPH cord-014597-66vd2mdu 1140 23 batch batch NN cord-014597-66vd2mdu 1140 24 cultures culture NNS cord-014597-66vd2mdu 1140 25 of of IN cord-014597-66vd2mdu 1140 26 rCHO rcho NN cord-014597-66vd2mdu 1140 27 cells cell NNS cord-014597-66vd2mdu 1140 28 . . . cord-014597-66vd2mdu 1141 1 Baicalein Baicalein NNP cord-014597-66vd2mdu 1141 2 addition addition NN cord-014597-66vd2mdu 1141 3 significantly significantly RB cord-014597-66vd2mdu 1141 4 enhanced enhance VBN cord-014597-66vd2mdu 1141 5 mAb mab NN cord-014597-66vd2mdu 1141 6 production production NN cord-014597-66vd2mdu 1141 7 while while IN cord-014597-66vd2mdu 1141 8 maintaining maintain VBG cord-014597-66vd2mdu 1141 9 galactosylated galactosylated JJ cord-014597-66vd2mdu 1141 10 forms form NNS cord-014597-66vd2mdu 1141 11 of of IN cord-014597-66vd2mdu 1141 12 mAb mab NN cord-014597-66vd2mdu 1141 13 . . . cord-014597-66vd2mdu 1142 1 Thus thus RB cord-014597-66vd2mdu 1142 2 , , , cord-014597-66vd2mdu 1142 3 baicalein baicalein NNP cord-014597-66vd2mdu 1142 4 is be VBZ cord-014597-66vd2mdu 1142 5 an an DT cord-014597-66vd2mdu 1142 6 effective effective JJ cord-014597-66vd2mdu 1142 7 antioxidant antioxidant NN cord-014597-66vd2mdu 1142 8 for for IN cord-014597-66vd2mdu 1142 9 use use NN cord-014597-66vd2mdu 1142 10 in in IN cord-014597-66vd2mdu 1142 11 rCHO rcho JJ cord-014597-66vd2mdu 1142 12 cell cell NN cord-014597-66vd2mdu 1142 13 cultures culture NNS cord-014597-66vd2mdu 1142 14 for for IN cord-014597-66vd2mdu 1142 15 improved improve VBN cord-014597-66vd2mdu 1142 16 mAb mab NN cord-014597-66vd2mdu 1142 17 production production NN cord-014597-66vd2mdu 1142 18 . . . cord-014597-66vd2mdu 1143 1 Background background NN cord-014597-66vd2mdu 1144 1 The the DT cord-014597-66vd2mdu 1144 2 production production NN cord-014597-66vd2mdu 1144 3 of of IN cord-014597-66vd2mdu 1144 4 many many JJ cord-014597-66vd2mdu 1144 5 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 1144 6 ( ( -LRB- cord-014597-66vd2mdu 1144 7 e.g. e.g. NNP cord-014597-66vd2mdu 1144 8 antibodies antibody NNS cord-014597-66vd2mdu 1144 9 & & CC cord-014597-66vd2mdu 1144 10 proteins protein NNS cord-014597-66vd2mdu 1144 11 for for IN cord-014597-66vd2mdu 1144 12 diagnostic diagnostic JJ cord-014597-66vd2mdu 1144 13 and and CC cord-014597-66vd2mdu 1144 14 therapeutic therapeutic JJ cord-014597-66vd2mdu 1144 15 purposes purpose NNS cord-014597-66vd2mdu 1144 16 ) ) -RRB- cord-014597-66vd2mdu 1144 17 requires require VBZ cord-014597-66vd2mdu 1144 18 the the DT cord-014597-66vd2mdu 1144 19 cultivation cultivation NN cord-014597-66vd2mdu 1144 20 of of IN cord-014597-66vd2mdu 1144 21 mammalian mammalian JJ cord-014597-66vd2mdu 1144 22 cell cell NN cord-014597-66vd2mdu 1144 23 lines line NNS cord-014597-66vd2mdu 1144 24 , , , cord-014597-66vd2mdu 1144 25 which which WDT cord-014597-66vd2mdu 1144 26 is be VBZ cord-014597-66vd2mdu 1144 27 demanding demand VBG cord-014597-66vd2mdu 1144 28 with with IN cord-014597-66vd2mdu 1144 29 respect respect NN cord-014597-66vd2mdu 1144 30 to to IN cord-014597-66vd2mdu 1144 31 various various JJ cord-014597-66vd2mdu 1144 32 aspects aspect NNS cord-014597-66vd2mdu 1144 33 such such JJ cord-014597-66vd2mdu 1144 34 as as IN cord-014597-66vd2mdu 1144 35 complex complex JJ cord-014597-66vd2mdu 1144 36 cell cell NN cord-014597-66vd2mdu 1144 37 metabolism metabolism NN cord-014597-66vd2mdu 1144 38 , , , cord-014597-66vd2mdu 1144 39 variabilities variability NNS cord-014597-66vd2mdu 1144 40 in in IN cord-014597-66vd2mdu 1144 41 cell cell NN cord-014597-66vd2mdu 1144 42 behavior behavior NN cord-014597-66vd2mdu 1144 43 , , , cord-014597-66vd2mdu 1144 44 scale scale VB cord-014597-66vd2mdu 1144 45 dependencies dependency NNS cord-014597-66vd2mdu 1144 46 , , , cord-014597-66vd2mdu 1144 47 influences influence NNS cord-014597-66vd2mdu 1144 48 of of IN cord-014597-66vd2mdu 1144 49 changes change NNS cord-014597-66vd2mdu 1144 50 in in IN cord-014597-66vd2mdu 1144 51 cultivation cultivation NN cord-014597-66vd2mdu 1144 52 conditions condition NNS cord-014597-66vd2mdu 1144 53 , , , cord-014597-66vd2mdu 1144 54 medium medium JJ cord-014597-66vd2mdu 1144 55 composition composition NN cord-014597-66vd2mdu 1144 56 etc etc FW cord-014597-66vd2mdu 1144 57 . . . cord-014597-66vd2mdu 1145 1 Although although IN cord-014597-66vd2mdu 1145 2 an an DT cord-014597-66vd2mdu 1145 3 increasing increase VBG cord-014597-66vd2mdu 1145 4 number number NN cord-014597-66vd2mdu 1145 5 of of IN cord-014597-66vd2mdu 1145 6 measurement measurement NN cord-014597-66vd2mdu 1145 7 parameters parameter NNS cord-014597-66vd2mdu 1145 8 is be VBZ cord-014597-66vd2mdu 1145 9 available available JJ cord-014597-66vd2mdu 1145 10 , , , cord-014597-66vd2mdu 1145 11 only only RB cord-014597-66vd2mdu 1145 12 a a DT cord-014597-66vd2mdu 1145 13 part part NN cord-014597-66vd2mdu 1145 14 of of IN cord-014597-66vd2mdu 1145 15 them -PRON- PRP cord-014597-66vd2mdu 1145 16 is be VBZ cord-014597-66vd2mdu 1145 17 routinely routinely RB cord-014597-66vd2mdu 1145 18 utilized utilize VBN cord-014597-66vd2mdu 1145 19 in in IN cord-014597-66vd2mdu 1145 20 industrial industrial JJ cord-014597-66vd2mdu 1145 21 cell cell NN cord-014597-66vd2mdu 1145 22 culture culture NN cord-014597-66vd2mdu 1145 23 processes process NNS cord-014597-66vd2mdu 1145 24 and and CC cord-014597-66vd2mdu 1145 25 their -PRON- PRP$ cord-014597-66vd2mdu 1145 26 corresponding correspond VBG cord-014597-66vd2mdu 1145 27 seed seed NN cord-014597-66vd2mdu 1145 28 trains train NNS cord-014597-66vd2mdu 1145 29 . . . cord-014597-66vd2mdu 1146 1 Nevertheless nevertheless RB cord-014597-66vd2mdu 1146 2 , , , cord-014597-66vd2mdu 1146 3 the the DT cord-014597-66vd2mdu 1146 4 data data NN cord-014597-66vd2mdu 1146 5 base base NN cord-014597-66vd2mdu 1146 6 grows grow VBZ cord-014597-66vd2mdu 1146 7 , , , cord-014597-66vd2mdu 1146 8 statistical statistical JJ cord-014597-66vd2mdu 1146 9 investigation investigation NN cord-014597-66vd2mdu 1146 10 of of IN cord-014597-66vd2mdu 1146 11 data data NN cord-014597-66vd2mdu 1146 12 gains gain VBZ cord-014597-66vd2mdu 1146 13 importance importance NN cord-014597-66vd2mdu 1146 14 and and CC cord-014597-66vd2mdu 1146 15 process process NN cord-014597-66vd2mdu 1146 16 data datum NNS cord-014597-66vd2mdu 1146 17 are be VBP cord-014597-66vd2mdu 1146 18 more more RBR cord-014597-66vd2mdu 1146 19 easily easily RB cord-014597-66vd2mdu 1146 20 accessible accessible JJ cord-014597-66vd2mdu 1146 21 in in IN cord-014597-66vd2mdu 1146 22 the the DT cord-014597-66vd2mdu 1146 23 context context NN cord-014597-66vd2mdu 1146 24 of of IN cord-014597-66vd2mdu 1146 25 industry industry NN cord-014597-66vd2mdu 1146 26 4.0 4.0 CD cord-014597-66vd2mdu 1146 27 . . . cord-014597-66vd2mdu 1147 1 Cell cell NN cord-014597-66vd2mdu 1147 2 cultivation cultivation NN cord-014597-66vd2mdu 1147 3 has have VBZ cord-014597-66vd2mdu 1147 4 to to TO cord-014597-66vd2mdu 1147 5 consider consider VB cord-014597-66vd2mdu 1147 6 these these DT cord-014597-66vd2mdu 1147 7 complex complex JJ cord-014597-66vd2mdu 1147 8 requirements requirement NNS cord-014597-66vd2mdu 1147 9 , , , cord-014597-66vd2mdu 1147 10 e.g. e.g. RB cord-014597-66vd2mdu 1147 11 for for IN cord-014597-66vd2mdu 1147 12 fed fed NN cord-014597-66vd2mdu 1147 13 - - HYPH cord-014597-66vd2mdu 1147 14 batch batch NN cord-014597-66vd2mdu 1147 15 control control NN cord-014597-66vd2mdu 1147 16 and and CC cord-014597-66vd2mdu 1147 17 seed seed NN cord-014597-66vd2mdu 1147 18 train train NN cord-014597-66vd2mdu 1147 19 design design NN cord-014597-66vd2mdu 1147 20 . . . cord-014597-66vd2mdu 1148 1 Furthermore furthermore RB cord-014597-66vd2mdu 1148 2 , , , cord-014597-66vd2mdu 1148 3 cultivation cultivation NN cord-014597-66vd2mdu 1148 4 strategies strategy NNS cord-014597-66vd2mdu 1148 5 have have VBP cord-014597-66vd2mdu 1148 6 to to TO cord-014597-66vd2mdu 1148 7 be be VB cord-014597-66vd2mdu 1148 8 adapted adapt VBN cord-014597-66vd2mdu 1148 9 to to IN cord-014597-66vd2mdu 1148 10 new new JJ cord-014597-66vd2mdu 1148 11 products product NNS cord-014597-66vd2mdu 1148 12 , , , cord-014597-66vd2mdu 1148 13 cell cell NN cord-014597-66vd2mdu 1148 14 lines line NNS cord-014597-66vd2mdu 1148 15 and and CC cord-014597-66vd2mdu 1148 16 clones clone NNS cord-014597-66vd2mdu 1148 17 as as RB cord-014597-66vd2mdu 1148 18 well well RB cord-014597-66vd2mdu 1148 19 as as IN cord-014597-66vd2mdu 1148 20 to to IN cord-014597-66vd2mdu 1148 21 different different JJ cord-014597-66vd2mdu 1148 22 production production NN cord-014597-66vd2mdu 1148 23 plants plant NNS cord-014597-66vd2mdu 1148 24 when when WRB cord-014597-66vd2mdu 1148 25 transferring transfer VBG cord-014597-66vd2mdu 1148 26 processes process NNS cord-014597-66vd2mdu 1148 27 . . . cord-014597-66vd2mdu 1149 1 One one CD cord-014597-66vd2mdu 1149 2 approach approach NN cord-014597-66vd2mdu 1149 3 to to TO cord-014597-66vd2mdu 1149 4 encounter encounter VB cord-014597-66vd2mdu 1149 5 the the DT cord-014597-66vd2mdu 1149 6 variabilities variability NNS cord-014597-66vd2mdu 1149 7 and and CC cord-014597-66vd2mdu 1149 8 to to TO cord-014597-66vd2mdu 1149 9 include include VB cord-014597-66vd2mdu 1149 10 actual actual JJ cord-014597-66vd2mdu 1149 11 information information NN cord-014597-66vd2mdu 1149 12 from from IN cord-014597-66vd2mdu 1149 13 the the DT cord-014597-66vd2mdu 1149 14 process process NN cord-014597-66vd2mdu 1149 15 and and CC cord-014597-66vd2mdu 1149 16 from from IN cord-014597-66vd2mdu 1149 17 data datum NNS cord-014597-66vd2mdu 1149 18 analysis analysis NN cord-014597-66vd2mdu 1149 19 is be VBZ cord-014597-66vd2mdu 1149 20 adaptive adaptive JJ cord-014597-66vd2mdu 1149 21 model model NN cord-014597-66vd2mdu 1149 22 - - HYPH cord-014597-66vd2mdu 1149 23 assisted assist VBN cord-014597-66vd2mdu 1149 24 control control NN cord-014597-66vd2mdu 1149 25 [ [ -LRB- cord-014597-66vd2mdu 1149 26 1 1 CD cord-014597-66vd2mdu 1149 27 ] ] -RRB- cord-014597-66vd2mdu 1149 28 . . . cord-014597-66vd2mdu 1150 1 Two two CD cord-014597-66vd2mdu 1150 2 software software NN cord-014597-66vd2mdu 1150 3 tools tool NNS cord-014597-66vd2mdu 1150 4 enabling enable VBG cord-014597-66vd2mdu 1150 5 adaptive adaptive JJ cord-014597-66vd2mdu 1150 6 model model NN cord-014597-66vd2mdu 1150 7 - - HYPH cord-014597-66vd2mdu 1150 8 assisted assist VBN cord-014597-66vd2mdu 1150 9 control control NN cord-014597-66vd2mdu 1150 10 applying apply VBG cord-014597-66vd2mdu 1150 11 unstructured unstructured JJ cord-014597-66vd2mdu 1150 12 , , , cord-014597-66vd2mdu 1150 13 unsegregated unsegregated JJ cord-014597-66vd2mdu 1150 14 models model NNS cord-014597-66vd2mdu 1150 15 have have VBP cord-014597-66vd2mdu 1150 16 been be VBN cord-014597-66vd2mdu 1150 17 developed develop VBN cord-014597-66vd2mdu 1150 18 and and CC cord-014597-66vd2mdu 1150 19 implemented implement VBN cord-014597-66vd2mdu 1150 20 using use VBG cord-014597-66vd2mdu 1150 21 MATLAB MATLAB NNP cord-014597-66vd2mdu 1150 22 © © NNP cord-014597-66vd2mdu 1150 23 , , , cord-014597-66vd2mdu 1150 24 WinErs WinErs NNP cord-014597-66vd2mdu 1150 25 and and CC cord-014597-66vd2mdu 1150 26 Fortran Fortran NNP cord-014597-66vd2mdu 1150 27 , , , cord-014597-66vd2mdu 1150 28 one one CD cord-014597-66vd2mdu 1150 29 tool tool NN cord-014597-66vd2mdu 1150 30 for for IN cord-014597-66vd2mdu 1150 31 fedbatch fedbatch NN cord-014597-66vd2mdu 1150 32 control control NN cord-014597-66vd2mdu 1150 33 and and CC cord-014597-66vd2mdu 1150 34 another another DT cord-014597-66vd2mdu 1150 35 one one NN cord-014597-66vd2mdu 1150 36 for for IN cord-014597-66vd2mdu 1150 37 seed seed NN cord-014597-66vd2mdu 1150 38 train train NN cord-014597-66vd2mdu 1150 39 simulation simulation NN cord-014597-66vd2mdu 1150 40 and and CC cord-014597-66vd2mdu 1150 41 optimization optimization NN cord-014597-66vd2mdu 1150 42 . . . cord-014597-66vd2mdu 1151 1 One one CD cord-014597-66vd2mdu 1151 2 key key JJ cord-014597-66vd2mdu 1151 3 element element NN cord-014597-66vd2mdu 1151 4 of of IN cord-014597-66vd2mdu 1151 5 adaptive adaptive JJ cord-014597-66vd2mdu 1151 6 model model NN cord-014597-66vd2mdu 1151 7 - - HYPH cord-014597-66vd2mdu 1151 8 assisted assist VBN cord-014597-66vd2mdu 1151 9 control control NN cord-014597-66vd2mdu 1151 10 is be VBZ cord-014597-66vd2mdu 1151 11 the the DT cord-014597-66vd2mdu 1151 12 underlying underlying JJ cord-014597-66vd2mdu 1151 13 process process NN cord-014597-66vd2mdu 1151 14 model model NN cord-014597-66vd2mdu 1151 15 . . . cord-014597-66vd2mdu 1152 1 In in IN cord-014597-66vd2mdu 1152 2 order order NN cord-014597-66vd2mdu 1152 3 to to TO cord-014597-66vd2mdu 1152 4 provide provide VB cord-014597-66vd2mdu 1152 5 an an DT cord-014597-66vd2mdu 1152 6 adaptive adaptive JJ cord-014597-66vd2mdu 1152 7 character character NN cord-014597-66vd2mdu 1152 8 , , , cord-014597-66vd2mdu 1152 9 model model NN cord-014597-66vd2mdu 1152 10 parameters parameter NNS cord-014597-66vd2mdu 1152 11 should should MD cord-014597-66vd2mdu 1152 12 be be VB cord-014597-66vd2mdu 1152 13 easily easily RB cord-014597-66vd2mdu 1152 14 identifiable identifiable JJ cord-014597-66vd2mdu 1152 15 from from IN cord-014597-66vd2mdu 1152 16 routine routine JJ cord-014597-66vd2mdu 1152 17 cultivation cultivation NN cord-014597-66vd2mdu 1152 18 data datum NNS cord-014597-66vd2mdu 1152 19 , , , cord-014597-66vd2mdu 1152 20 which which WDT cord-014597-66vd2mdu 1152 21 is be VBZ cord-014597-66vd2mdu 1152 22 available available JJ cord-014597-66vd2mdu 1152 23 during during IN cord-014597-66vd2mdu 1152 24 seed seed NN cord-014597-66vd2mdu 1152 25 train train NN cord-014597-66vd2mdu 1152 26 and and CC cord-014597-66vd2mdu 1152 27 fed fed NN cord-014597-66vd2mdu 1152 28 - - HYPH cord-014597-66vd2mdu 1152 29 batch batch NN cord-014597-66vd2mdu 1152 30 without without IN cord-014597-66vd2mdu 1152 31 additional additional JJ cord-014597-66vd2mdu 1152 32 sophisticated sophisticated JJ cord-014597-66vd2mdu 1152 33 measurements measurement NNS cord-014597-66vd2mdu 1152 34 . . . cord-014597-66vd2mdu 1153 1 Therefore therefore RB cord-014597-66vd2mdu 1153 2 , , , cord-014597-66vd2mdu 1153 3 the the DT cord-014597-66vd2mdu 1153 4 usage usage NN cord-014597-66vd2mdu 1153 5 of of IN cord-014597-66vd2mdu 1153 6 unstructured unstructured JJ cord-014597-66vd2mdu 1153 7 , , , cord-014597-66vd2mdu 1153 8 unsegregated unsegregated JJ cord-014597-66vd2mdu 1153 9 models model NNS cord-014597-66vd2mdu 1153 10 is be VBZ cord-014597-66vd2mdu 1153 11 recommended recommend VBN cord-014597-66vd2mdu 1153 12 . . . cord-014597-66vd2mdu 1154 1 a a LS cord-014597-66vd2mdu 1154 2 ) ) -RRB- cord-014597-66vd2mdu 1155 1 Example example NN cord-014597-66vd2mdu 1155 2 of of IN cord-014597-66vd2mdu 1155 3 an an DT cord-014597-66vd2mdu 1155 4 unstructured unstructured JJ cord-014597-66vd2mdu 1155 5 , , , cord-014597-66vd2mdu 1155 6 unsegregated unsegregated JJ cord-014597-66vd2mdu 1155 7 cell cell NN cord-014597-66vd2mdu 1155 8 culture culture NN cord-014597-66vd2mdu 1155 9 model model NN cord-014597-66vd2mdu 1155 10 ( ( -LRB- cord-014597-66vd2mdu 1155 11 for for IN cord-014597-66vd2mdu 1155 12 adaptive adaptive JJ cord-014597-66vd2mdu 1155 13 model model NN cord-014597-66vd2mdu 1155 14 - - HYPH cord-014597-66vd2mdu 1155 15 assisted assist VBN cord-014597-66vd2mdu 1155 16 control control NN cord-014597-66vd2mdu 1155 17 ) ) -RRB- cord-014597-66vd2mdu 1156 1 One one CD cord-014597-66vd2mdu 1156 2 example example NN cord-014597-66vd2mdu 1156 3 , , , cord-014597-66vd2mdu 1156 4 describing describe VBG cord-014597-66vd2mdu 1156 5 cell cell NN cord-014597-66vd2mdu 1156 6 growth growth NN cord-014597-66vd2mdu 1156 7 , , , cord-014597-66vd2mdu 1156 8 cell cell NN cord-014597-66vd2mdu 1156 9 death death NN cord-014597-66vd2mdu 1156 10 , , , cord-014597-66vd2mdu 1156 11 uptake uptake NN cord-014597-66vd2mdu 1156 12 of of IN cord-014597-66vd2mdu 1156 13 substrates substrate NNS cord-014597-66vd2mdu 1156 14 and and CC cord-014597-66vd2mdu 1156 15 production production NN cord-014597-66vd2mdu 1156 16 of of IN cord-014597-66vd2mdu 1156 17 metabolites metabolite NNS cord-014597-66vd2mdu 1156 18 via via IN cord-014597-66vd2mdu 1156 19 a a DT cord-014597-66vd2mdu 1156 20 first first JJ cord-014597-66vd2mdu 1156 21 order order NN cord-014597-66vd2mdu 1156 22 system system NN cord-014597-66vd2mdu 1156 23 of of IN cord-014597-66vd2mdu 1156 24 ordinary ordinary JJ cord-014597-66vd2mdu 1156 25 differential differential JJ cord-014597-66vd2mdu 1156 26 equations equation NNS cord-014597-66vd2mdu 1156 27 and and CC cord-014597-66vd2mdu 1156 28 Monod Monod NNP cord-014597-66vd2mdu 1156 29 - - HYPH cord-014597-66vd2mdu 1156 30 type type NN cord-014597-66vd2mdu 1156 31 kinetics kinetics NN cord-014597-66vd2mdu 1156 32 , , , cord-014597-66vd2mdu 1156 33 is be VBZ cord-014597-66vd2mdu 1156 34 shown show VBN cord-014597-66vd2mdu 1156 35 in in IN cord-014597-66vd2mdu 1156 36 Table Table NNP cord-014597-66vd2mdu 1156 37 1 1 CD cord-014597-66vd2mdu 1156 38 . . . cord-014597-66vd2mdu 1157 1 This this DT cord-014597-66vd2mdu 1157 2 mathematical mathematical JJ cord-014597-66vd2mdu 1157 3 model model NN cord-014597-66vd2mdu 1157 4 includes include VBZ cord-014597-66vd2mdu 1157 5 13 13 CD cord-014597-66vd2mdu 1157 6 cell cell NN cord-014597-66vd2mdu 1157 7 specific specific JJ cord-014597-66vd2mdu 1157 8 model model NN cord-014597-66vd2mdu 1157 9 parameters parameter NNS cord-014597-66vd2mdu 1157 10 [ [ -LRB- cord-014597-66vd2mdu 1157 11 2 2 CD cord-014597-66vd2mdu 1157 12 ] ] -RRB- cord-014597-66vd2mdu 1157 13 . . . cord-014597-66vd2mdu 1158 1 ii ii LS cord-014597-66vd2mdu 1158 2 ) ) -RRB- cord-014597-66vd2mdu 1158 3 b b LS cord-014597-66vd2mdu 1158 4 ) ) -RRB- cord-014597-66vd2mdu 1158 5 Open open JJ cord-014597-66vd2mdu 1158 6 - - HYPH cord-014597-66vd2mdu 1158 7 loop loop NN cord-014597-66vd2mdu 1158 8 control control NN cord-014597-66vd2mdu 1158 9 sequence sequence NN cord-014597-66vd2mdu 1158 10 for for IN cord-014597-66vd2mdu 1158 11 seed seed NN cord-014597-66vd2mdu 1158 12 train train NN cord-014597-66vd2mdu 1158 13 simulation simulation NN cord-014597-66vd2mdu 1158 14 and and CC cord-014597-66vd2mdu 1158 15 optimization optimization NN cord-014597-66vd2mdu 1158 16 [ [ -LRB- cord-014597-66vd2mdu 1158 17 3 3 CD cord-014597-66vd2mdu 1158 18 ] ] -RRB- cord-014597-66vd2mdu 1158 19 : : : cord-014597-66vd2mdu 1159 1 Using use VBG cord-014597-66vd2mdu 1159 2 model model NN cord-014597-66vd2mdu 1159 3 , , , cord-014597-66vd2mdu 1159 4 a a FW cord-014597-66vd2mdu 1159 5 priori priori FW cord-014597-66vd2mdu 1159 6 identified identify VBN cord-014597-66vd2mdu 1159 7 model model NN cord-014597-66vd2mdu 1159 8 parameters parameter NNS cord-014597-66vd2mdu 1159 9 and and CC cord-014597-66vd2mdu 1159 10 starting start VBG cord-014597-66vd2mdu 1159 11 concentration concentration NN cord-014597-66vd2mdu 1159 12 values value NNS cord-014597-66vd2mdu 1159 13 , , , cord-014597-66vd2mdu 1159 14 the the DT cord-014597-66vd2mdu 1159 15 temporal temporal JJ cord-014597-66vd2mdu 1159 16 concentration concentration NN cord-014597-66vd2mdu 1159 17 courses course NNS cord-014597-66vd2mdu 1159 18 can can MD cord-014597-66vd2mdu 1159 19 be be VB cord-014597-66vd2mdu 1159 20 predicted predict VBN cord-014597-66vd2mdu 1159 21 for for IN cord-014597-66vd2mdu 1159 22 the the DT cord-014597-66vd2mdu 1159 23 first first JJ cord-014597-66vd2mdu 1159 24 scale scale NN cord-014597-66vd2mdu 1159 25 . . . cord-014597-66vd2mdu 1160 1 Subsequently subsequently RB cord-014597-66vd2mdu 1160 2 , , , cord-014597-66vd2mdu 1160 3 points point NNS cord-014597-66vd2mdu 1160 4 in in IN cord-014597-66vd2mdu 1160 5 time time NN cord-014597-66vd2mdu 1160 6 for for IN cord-014597-66vd2mdu 1160 7 passaging passaging NN cord-014597-66vd2mdu 1160 8 and and CC cord-014597-66vd2mdu 1160 9 starting start VBG cord-014597-66vd2mdu 1160 10 values value NNS cord-014597-66vd2mdu 1160 11 for for IN cord-014597-66vd2mdu 1160 12 the the DT cord-014597-66vd2mdu 1160 13 next next JJ cord-014597-66vd2mdu 1160 14 scale scale NN cord-014597-66vd2mdu 1160 15 can can MD cord-014597-66vd2mdu 1160 16 be be VB cord-014597-66vd2mdu 1160 17 computed compute VBN cord-014597-66vd2mdu 1160 18 by by IN cord-014597-66vd2mdu 1160 19 adding add VBG cord-014597-66vd2mdu 1160 20 a a DT cord-014597-66vd2mdu 1160 21 passaging passaging NN cord-014597-66vd2mdu 1160 22 strategy strategy NN cord-014597-66vd2mdu 1160 23 , , , cord-014597-66vd2mdu 1160 24 seed seed NN cord-014597-66vd2mdu 1160 25 train train NN cord-014597-66vd2mdu 1160 26 conditions condition NNS cord-014597-66vd2mdu 1160 27 and and CC cord-014597-66vd2mdu 1160 28 medium medium NN cord-014597-66vd2mdu 1160 29 concentrations concentration NNS cord-014597-66vd2mdu 1160 30 . . . cord-014597-66vd2mdu 1161 1 Prediction prediction NN cord-014597-66vd2mdu 1161 2 for for IN cord-014597-66vd2mdu 1161 3 the the DT cord-014597-66vd2mdu 1161 4 following follow VBG cord-014597-66vd2mdu 1161 5 scales scale NNS cord-014597-66vd2mdu 1161 6 can can MD cord-014597-66vd2mdu 1161 7 be be VB cord-014597-66vd2mdu 1161 8 obtained obtain VBN cord-014597-66vd2mdu 1161 9 iteratively iteratively RB cord-014597-66vd2mdu 1161 10 . . . cord-014597-66vd2mdu 1162 1 Integrating integrate VBG cord-014597-66vd2mdu 1162 2 feedback feedback NN cord-014597-66vd2mdu 1162 3 from from IN cord-014597-66vd2mdu 1162 4 the the DT cord-014597-66vd2mdu 1162 5 process process NN cord-014597-66vd2mdu 1162 6 in in IN cord-014597-66vd2mdu 1162 7 terms term NNS cord-014597-66vd2mdu 1162 8 of of IN cord-014597-66vd2mdu 1162 9 cultivation cultivation NN cord-014597-66vd2mdu 1162 10 data datum NNS cord-014597-66vd2mdu 1162 11 enables enable VBZ cord-014597-66vd2mdu 1162 12 increasing increase VBG cord-014597-66vd2mdu 1162 13 prediction prediction NN cord-014597-66vd2mdu 1162 14 accuracy accuracy NN cord-014597-66vd2mdu 1162 15 and and CC cord-014597-66vd2mdu 1162 16 responding respond VBG cord-014597-66vd2mdu 1162 17 to to IN cord-014597-66vd2mdu 1162 18 possible possible JJ cord-014597-66vd2mdu 1162 19 changes change NNS cord-014597-66vd2mdu 1162 20 in in IN cord-014597-66vd2mdu 1162 21 cell cell NN cord-014597-66vd2mdu 1162 22 behaviour behaviour NN cord-014597-66vd2mdu 1162 23 . . . cord-014597-66vd2mdu 1163 1 Process process NN cord-014597-66vd2mdu 1163 2 design design NN cord-014597-66vd2mdu 1163 3 and and CC cord-014597-66vd2mdu 1163 4 optimization optimization NN cord-014597-66vd2mdu 1163 5 , , , cord-014597-66vd2mdu 1164 1 e.g. e.g. RB cord-014597-66vd2mdu 1164 2 regarding regard VBG cord-014597-66vd2mdu 1164 3 seed seed NN cord-014597-66vd2mdu 1164 4 train train NN cord-014597-66vd2mdu 1164 5 and and CC cord-014597-66vd2mdu 1164 6 fed fed NN cord-014597-66vd2mdu 1164 7 - - HYPH cord-014597-66vd2mdu 1164 8 batch batch NN cord-014597-66vd2mdu 1164 9 , , , cord-014597-66vd2mdu 1164 10 is be VBZ cord-014597-66vd2mdu 1164 11 realized realize VBN cord-014597-66vd2mdu 1164 12 by by IN cord-014597-66vd2mdu 1164 13 adaptive adaptive JJ cord-014597-66vd2mdu 1164 14 model model NN cord-014597-66vd2mdu 1164 15 - - HYPH cord-014597-66vd2mdu 1164 16 assisted assist VBN cord-014597-66vd2mdu 1164 17 software software NN cord-014597-66vd2mdu 1164 18 tools tool NNS cord-014597-66vd2mdu 1164 19 using use VBG cord-014597-66vd2mdu 1164 20 unstructured unstructured JJ cord-014597-66vd2mdu 1164 21 , , , cord-014597-66vd2mdu 1164 22 unsegregated unsegregated JJ cord-014597-66vd2mdu 1164 23 models model NNS cord-014597-66vd2mdu 1164 24 . . . cord-014597-66vd2mdu 1165 1 They -PRON- PRP cord-014597-66vd2mdu 1165 2 enable enable VBP cord-014597-66vd2mdu 1165 3 feedback feedback NN cord-014597-66vd2mdu 1165 4 from from IN cord-014597-66vd2mdu 1165 5 the the DT cord-014597-66vd2mdu 1165 6 process process NN cord-014597-66vd2mdu 1165 7 via via IN cord-014597-66vd2mdu 1165 8 routine routine JJ cord-014597-66vd2mdu 1165 9 cultivation cultivation NN cord-014597-66vd2mdu 1165 10 data datum NNS cord-014597-66vd2mdu 1165 11 and and CC cord-014597-66vd2mdu 1165 12 allow allow VB cord-014597-66vd2mdu 1165 13 adaptation adaptation NN cord-014597-66vd2mdu 1165 14 to to IN cord-014597-66vd2mdu 1165 15 diverse diverse JJ cord-014597-66vd2mdu 1165 16 circumstances circumstance NNS cord-014597-66vd2mdu 1165 17 such such JJ cord-014597-66vd2mdu 1165 18 as as IN cord-014597-66vd2mdu 1165 19 different different JJ cord-014597-66vd2mdu 1165 20 cell cell NN cord-014597-66vd2mdu 1165 21 lines line NNS cord-014597-66vd2mdu 1165 22 , , , cord-014597-66vd2mdu 1165 23 products product NNS cord-014597-66vd2mdu 1165 24 , , , cord-014597-66vd2mdu 1165 25 cultivation cultivation NN cord-014597-66vd2mdu 1165 26 conditions condition NNS cord-014597-66vd2mdu 1165 27 , , , cord-014597-66vd2mdu 1165 28 plant plant NN cord-014597-66vd2mdu 1165 29 configurations configuration NNS cord-014597-66vd2mdu 1165 30 etc etc FW cord-014597-66vd2mdu 1165 31 . . . cord-014597-66vd2mdu 1165 32 ) ) -RRB- cord-014597-66vd2mdu 1166 1 in in IN cord-014597-66vd2mdu 1166 2 polyelectrolyte polyelectrolyte NNP cord-014597-66vd2mdu 1166 3 capsules capsule NNS cord-014597-66vd2mdu 1166 4 . . . cord-014597-66vd2mdu 1167 1 Significant significant JJ cord-014597-66vd2mdu 1167 2 advantages advantage NNS cord-014597-66vd2mdu 1167 3 , , , cord-014597-66vd2mdu 1167 4 such such JJ cord-014597-66vd2mdu 1167 5 as as IN cord-014597-66vd2mdu 1167 6 great great JJ cord-014597-66vd2mdu 1167 7 mechanical mechanical JJ cord-014597-66vd2mdu 1167 8 stability stability NN cord-014597-66vd2mdu 1167 9 , , , cord-014597-66vd2mdu 1167 10 good good JJ cord-014597-66vd2mdu 1167 11 biocompatibility biocompatibility NN cord-014597-66vd2mdu 1167 12 and and CC cord-014597-66vd2mdu 1167 13 good good JJ cord-014597-66vd2mdu 1167 14 mass mass NN cord-014597-66vd2mdu 1167 15 transfer transfer NN cord-014597-66vd2mdu 1167 16 properties property NNS cord-014597-66vd2mdu 1167 17 characterized characterize VBD cord-014597-66vd2mdu 1167 18 these these DT cord-014597-66vd2mdu 1167 19 capsules capsule NNS cord-014597-66vd2mdu 1167 20 based base VBN cord-014597-66vd2mdu 1167 21 on on IN cord-014597-66vd2mdu 1167 22 sodium sodium NN cord-014597-66vd2mdu 1167 23 cellulose cellulose NN cord-014597-66vd2mdu 1167 24 sulfate sulfate NN cord-014597-66vd2mdu 1167 25 / / SYM cord-014597-66vd2mdu 1167 26 poly(diallyldimethyl poly(diallyldimethyl NN cord-014597-66vd2mdu 1167 27 ) ) -RRB- cord-014597-66vd2mdu 1168 1 ammonium ammonium NN cord-014597-66vd2mdu 1168 2 chloride chloride NN cord-014597-66vd2mdu 1168 3 ( ( -LRB- cord-014597-66vd2mdu 1168 4 SCS SCS NNP cord-014597-66vd2mdu 1168 5 / / SYM cord-014597-66vd2mdu 1168 6 PDADMAC PDADMAC NNP cord-014597-66vd2mdu 1168 7 ) ) -RRB- cord-014597-66vd2mdu 1169 1 [ [ -LRB- cord-014597-66vd2mdu 1169 2 1 1 CD cord-014597-66vd2mdu 1169 3 , , , cord-014597-66vd2mdu 1169 4 2 2 CD cord-014597-66vd2mdu 1169 5 ] ] -RRB- cord-014597-66vd2mdu 1169 6 . . . cord-014597-66vd2mdu 1170 1 Here here RB cord-014597-66vd2mdu 1170 2 , , , cord-014597-66vd2mdu 1170 3 we -PRON- PRP cord-014597-66vd2mdu 1170 4 present present VBP cord-014597-66vd2mdu 1170 5 the the DT cord-014597-66vd2mdu 1170 6 possibility possibility NN cord-014597-66vd2mdu 1170 7 to to TO cord-014597-66vd2mdu 1170 8 cultivate cultivate VB cord-014597-66vd2mdu 1170 9 human human JJ cord-014597-66vd2mdu 1170 10 T t NN cord-014597-66vd2mdu 1170 11 cells cell NNS cord-014597-66vd2mdu 1170 12 , , , cord-014597-66vd2mdu 1170 13 freshly freshly RB cord-014597-66vd2mdu 1170 14 isolated isolate VBN cord-014597-66vd2mdu 1170 15 from from IN cord-014597-66vd2mdu 1170 16 blood blood NN cord-014597-66vd2mdu 1170 17 , , , cord-014597-66vd2mdu 1170 18 to to IN cord-014597-66vd2mdu 1170 19 high high JJ cord-014597-66vd2mdu 1170 20 densities density NNS cord-014597-66vd2mdu 1170 21 in in IN cord-014597-66vd2mdu 1170 22 similar similar JJ cord-014597-66vd2mdu 1170 23 semipermeable semipermeable JJ cord-014597-66vd2mdu 1170 24 polyelectrolyte polyelectrolyte NN cord-014597-66vd2mdu 1170 25 microcapsules microcapsules NNP cord-014597-66vd2mdu 1170 26 within within IN cord-014597-66vd2mdu 1170 27 less less JJR cord-014597-66vd2mdu 1170 28 than than IN cord-014597-66vd2mdu 1170 29 10 10 CD cord-014597-66vd2mdu 1170 30 days day NNS cord-014597-66vd2mdu 1170 31 . . . cord-014597-66vd2mdu 1171 1 Cells cell NNS cord-014597-66vd2mdu 1171 2 were be VBD cord-014597-66vd2mdu 1171 3 encapsulated encapsulate VBN cord-014597-66vd2mdu 1171 4 in in IN cord-014597-66vd2mdu 1171 5 semipermeable semipermeable JJ cord-014597-66vd2mdu 1171 6 SCS SCS NNP cord-014597-66vd2mdu 1171 7 / / SYM cord-014597-66vd2mdu 1171 8 PDADMAC PDADMAC NNP cord-014597-66vd2mdu 1171 9 polyelectrolyte polyelectrolyte NN cord-014597-66vd2mdu 1171 10 microcapsules microcapsule NNS cord-014597-66vd2mdu 1171 11 or or CC cord-014597-66vd2mdu 1171 12 confined confine VBN cord-014597-66vd2mdu 1171 13 in in IN cord-014597-66vd2mdu 1171 14 1.5 1.5 CD cord-014597-66vd2mdu 1171 15 % % NN cord-014597-66vd2mdu 1171 16 alginate alginate NN cord-014597-66vd2mdu 1171 17 / / SYM cord-014597-66vd2mdu 1171 18 poly poly JJ cord-014597-66vd2mdu 1171 19 - - HYPH cord-014597-66vd2mdu 1171 20 l l NN cord-014597-66vd2mdu 1171 21 - - HYPH cord-014597-66vd2mdu 1171 22 lysine lysine NN cord-014597-66vd2mdu 1171 23 ( ( -LRB- cord-014597-66vd2mdu 1171 24 PLL PLL NNP cord-014597-66vd2mdu 1171 25 ) ) -RRB- cord-014597-66vd2mdu 1171 26 beads bead NNS cord-014597-66vd2mdu 1171 27 , , , cord-014597-66vd2mdu 1171 28 a a DT cord-014597-66vd2mdu 1171 29 standard standard JJ cord-014597-66vd2mdu 1171 30 approach approach NN cord-014597-66vd2mdu 1171 31 for for IN cord-014597-66vd2mdu 1171 32 cell cell NN cord-014597-66vd2mdu 1171 33 immobilization immobilization NN cord-014597-66vd2mdu 1171 34 . . . cord-014597-66vd2mdu 1172 1 The the DT cord-014597-66vd2mdu 1172 2 permeability permeability NN cord-014597-66vd2mdu 1172 3 of of IN cord-014597-66vd2mdu 1172 4 the the DT cord-014597-66vd2mdu 1172 5 microcapsules microcapsule NNS cord-014597-66vd2mdu 1172 6 was be VBD cord-014597-66vd2mdu 1172 7 estimated estimate VBN cord-014597-66vd2mdu 1172 8 using use VBG cord-014597-66vd2mdu 1172 9 dextran dextran NN cord-014597-66vd2mdu 1172 10 - - HYPH cord-014597-66vd2mdu 1172 11 based base VBN cord-014597-66vd2mdu 1172 12 molecular molecular JJ cord-014597-66vd2mdu 1172 13 weight weight NN cord-014597-66vd2mdu 1172 14 standards standard NNS cord-014597-66vd2mdu 1172 15 ( ( -LRB- cord-014597-66vd2mdu 1172 16 10 10 CD cord-014597-66vd2mdu 1172 17 and and CC cord-014597-66vd2mdu 1172 18 20 20 CD cord-014597-66vd2mdu 1172 19 kDa kDa NNS cord-014597-66vd2mdu 1172 20 ) ) -RRB- cord-014597-66vd2mdu 1172 21 and and CC cord-014597-66vd2mdu 1172 22 vitamin vitamin NN cord-014597-66vd2mdu 1172 23 B12 b12 NN cord-014597-66vd2mdu 1172 24 ( ( -LRB- cord-014597-66vd2mdu 1172 25 1.6 1.6 CD cord-014597-66vd2mdu 1172 26 kDa kDa NNS cord-014597-66vd2mdu 1172 27 ) ) -RRB- cord-014597-66vd2mdu 1172 28 . . . cord-014597-66vd2mdu 1173 1 Gentle gentle JJ cord-014597-66vd2mdu 1173 2 digestion digestion NN cord-014597-66vd2mdu 1173 3 with with IN cord-014597-66vd2mdu 1173 4 endocellulase endocellulase NN cord-014597-66vd2mdu 1173 5 allows allow VBZ cord-014597-66vd2mdu 1173 6 an an DT cord-014597-66vd2mdu 1173 7 easy easy JJ cord-014597-66vd2mdu 1173 8 release release NN cord-014597-66vd2mdu 1173 9 of of IN cord-014597-66vd2mdu 1173 10 the the DT cord-014597-66vd2mdu 1173 11 cells cell NNS cord-014597-66vd2mdu 1173 12 out out IN cord-014597-66vd2mdu 1173 13 of of IN cord-014597-66vd2mdu 1173 14 the the DT cord-014597-66vd2mdu 1173 15 capsules capsule NNS cord-014597-66vd2mdu 1173 16 . . . cord-014597-66vd2mdu 1174 1 Cell cell NN cord-014597-66vd2mdu 1174 2 growth growth NN cord-014597-66vd2mdu 1175 1 , , , cord-014597-66vd2mdu 1175 2 cytokines cytokine NNS cord-014597-66vd2mdu 1175 3 production production NN cord-014597-66vd2mdu 1175 4 and and CC cord-014597-66vd2mdu 1175 5 phenotype phenotype NN cord-014597-66vd2mdu 1175 6 were be VBD cord-014597-66vd2mdu 1175 7 measured measure VBN cord-014597-66vd2mdu 1175 8 in in IN cord-014597-66vd2mdu 1175 9 non non JJ cord-014597-66vd2mdu 1175 10 - - JJ cord-014597-66vd2mdu 1175 11 encapsulated encapsulated JJ cord-014597-66vd2mdu 1175 12 and and CC cord-014597-66vd2mdu 1175 13 encapsulated encapsulate VBN cord-014597-66vd2mdu 1175 14 cells cell NNS cord-014597-66vd2mdu 1175 15 grown grow VBN cord-014597-66vd2mdu 1175 16 under under IN cord-014597-66vd2mdu 1175 17 standard standard JJ cord-014597-66vd2mdu 1175 18 culture culture NN cord-014597-66vd2mdu 1175 19 conditions condition NNS cord-014597-66vd2mdu 1175 20 . . . cord-014597-66vd2mdu 1176 1 Moreover moreover RB cord-014597-66vd2mdu 1176 2 , , , cord-014597-66vd2mdu 1176 3 we -PRON- PRP cord-014597-66vd2mdu 1176 4 analyzed analyze VBD cord-014597-66vd2mdu 1176 5 the the DT cord-014597-66vd2mdu 1176 6 interplay interplay NN cord-014597-66vd2mdu 1176 7 between between IN cord-014597-66vd2mdu 1176 8 the the DT cord-014597-66vd2mdu 1176 9 secreted secrete VBN cord-014597-66vd2mdu 1176 10 cytokines cytokine NNS cord-014597-66vd2mdu 1176 11 and and CC cord-014597-66vd2mdu 1176 12 the the DT cord-014597-66vd2mdu 1176 13 SCS SCS NNP cord-014597-66vd2mdu 1176 14 within within IN cord-014597-66vd2mdu 1176 15 the the DT cord-014597-66vd2mdu 1176 16 capsules capsule NNS cord-014597-66vd2mdu 1176 17 and and CC cord-014597-66vd2mdu 1176 18 its -PRON- PRP$ cord-014597-66vd2mdu 1176 19 putative putative JJ cord-014597-66vd2mdu 1176 20 influence influence NN cord-014597-66vd2mdu 1176 21 on on IN cord-014597-66vd2mdu 1176 22 cell cell NN cord-014597-66vd2mdu 1176 23 growth growth NN cord-014597-66vd2mdu 1176 24 . . . cord-014597-66vd2mdu 1177 1 Cells cell NNS cord-014597-66vd2mdu 1177 2 mixed mix VBN cord-014597-66vd2mdu 1177 3 in in IN cord-014597-66vd2mdu 1177 4 the the DT cord-014597-66vd2mdu 1177 5 cellulose cellulose NN cord-014597-66vd2mdu 1177 6 sulfate sulfate NN cord-014597-66vd2mdu 1177 7 solution solution NN cord-014597-66vd2mdu 1177 8 under under IN cord-014597-66vd2mdu 1177 9 physiological physiological JJ cord-014597-66vd2mdu 1177 10 conditions condition NNS cord-014597-66vd2mdu 1177 11 can can MD cord-014597-66vd2mdu 1177 12 be be VB cord-014597-66vd2mdu 1177 13 safely safely RB cord-014597-66vd2mdu 1177 14 trapped trap VBN cord-014597-66vd2mdu 1177 15 within within IN cord-014597-66vd2mdu 1177 16 a a DT cord-014597-66vd2mdu 1177 17 liquid liquid JJ cord-014597-66vd2mdu 1177 18 core core NN cord-014597-66vd2mdu 1177 19 during during IN cord-014597-66vd2mdu 1177 20 capsule capsule NN cord-014597-66vd2mdu 1177 21 formation formation NN cord-014597-66vd2mdu 1177 22 . . . cord-014597-66vd2mdu 1178 1 Encapsulated encapsulate VBN cord-014597-66vd2mdu 1178 2 cells cell NNS cord-014597-66vd2mdu 1178 3 can can MD cord-014597-66vd2mdu 1178 4 reached reach VBN cord-014597-66vd2mdu 1178 5 cell cell NN cord-014597-66vd2mdu 1178 6 densities density NNS cord-014597-66vd2mdu 1178 7 ≤ ≤ NNP cord-014597-66vd2mdu 1178 8 40 40 CD cord-014597-66vd2mdu 1178 9 x x SYM cord-014597-66vd2mdu 1178 10 10 10 CD cord-014597-66vd2mdu 1178 11 6 6 CD cord-014597-66vd2mdu 1178 12 cells cell NNS cord-014597-66vd2mdu 1178 13 mL ml NN cord-014597-66vd2mdu 1178 14 capsule capsule NN cord-014597-66vd2mdu 1178 15 -1 -1 NN cord-014597-66vd2mdu 1178 16 , , , cord-014597-66vd2mdu 1178 17 whereas whereas IN cord-014597-66vd2mdu 1178 18 cells cell NNS cord-014597-66vd2mdu 1178 19 confined confine VBN cord-014597-66vd2mdu 1178 20 in in IN cord-014597-66vd2mdu 1178 21 alginate alginate NN cord-014597-66vd2mdu 1178 22 / / SYM cord-014597-66vd2mdu 1178 23 PLL pll JJ cord-014597-66vd2mdu 1178 24 beads bead NNS cord-014597-66vd2mdu 1178 25 and and CC cord-014597-66vd2mdu 1178 26 non non JJ cord-014597-66vd2mdu 1178 27 - - JJ cord-014597-66vd2mdu 1178 28 encapsulated encapsulated JJ cord-014597-66vd2mdu 1178 29 ones one NNS cord-014597-66vd2mdu 1178 30 reached reach VBD cord-014597-66vd2mdu 1178 31 11.3 11.3 CD cord-014597-66vd2mdu 1178 32 x x SYM cord-014597-66vd2mdu 1178 33 10 10 CD cord-014597-66vd2mdu 1178 34 6 6 CD cord-014597-66vd2mdu 1178 35 cells cell NNS cord-014597-66vd2mdu 1178 36 mL ml NN cord-014597-66vd2mdu 1178 37 bead bead NN cord-014597-66vd2mdu 1178 38 -1 -1 NN cord-014597-66vd2mdu 1178 39 and and CC cord-014597-66vd2mdu 1178 40 2.4 2.4 CD cord-014597-66vd2mdu 1178 41 x x SYM cord-014597-66vd2mdu 1178 42 10 10 CD cord-014597-66vd2mdu 1178 43 6 6 CD cord-014597-66vd2mdu 1178 44 cells cell NNS cord-014597-66vd2mdu 1178 45 mL ml NN cord-014597-66vd2mdu 1178 46 , , , cord-014597-66vd2mdu 1178 47 respectively respectively RB cord-014597-66vd2mdu 1178 48 . . . cord-014597-66vd2mdu 1179 1 One one CD cord-014597-66vd2mdu 1179 2 major major JJ cord-014597-66vd2mdu 1179 3 advantage advantage NN cord-014597-66vd2mdu 1179 4 of of IN cord-014597-66vd2mdu 1179 5 these these DT cord-014597-66vd2mdu 1179 6 polyelectrolyte polyelectrolyte NNP cord-014597-66vd2mdu 1179 7 microcapsules microcapsules NNP cord-014597-66vd2mdu 1179 8 ( ( -LRB- cord-014597-66vd2mdu 1179 9 < < NNP cord-014597-66vd2mdu 1179 10 1 1 CD cord-014597-66vd2mdu 1179 11 mm mm NNP cord-014597-66vd2mdu 1179 12 ) ) -RRB- cord-014597-66vd2mdu 1179 13 is be VBZ cord-014597-66vd2mdu 1179 14 the the DT cord-014597-66vd2mdu 1179 15 low low JJ cord-014597-66vd2mdu 1179 16 MWCO MWCO NNPS cord-014597-66vd2mdu 1179 17 ( ( -LRB- cord-014597-66vd2mdu 1179 18 < < NNP cord-014597-66vd2mdu 1179 19 10 10 CD cord-014597-66vd2mdu 1179 20 kDa kDa NNPS cord-014597-66vd2mdu 1179 21 ) ) -RRB- cord-014597-66vd2mdu 1180 1 ( ( -LRB- cord-014597-66vd2mdu 1180 2 Fig Fig NNP cord-014597-66vd2mdu 1180 3 . . . cord-014597-66vd2mdu 1180 4 1a 1a CD cord-014597-66vd2mdu 1180 5 - - HYPH cord-014597-66vd2mdu 1180 6 b b NN cord-014597-66vd2mdu 1180 7 ) ) -RRB- cord-014597-66vd2mdu 1180 8 . . . cord-014597-66vd2mdu 1181 1 This this DT cord-014597-66vd2mdu 1181 2 restricted restricted JJ cord-014597-66vd2mdu 1181 3 permeability permeability NN cord-014597-66vd2mdu 1181 4 allows allow VBZ cord-014597-66vd2mdu 1181 5 for for IN cord-014597-66vd2mdu 1181 6 a a DT cord-014597-66vd2mdu 1181 7 conditioning conditioning NN cord-014597-66vd2mdu 1181 8 of of IN cord-014597-66vd2mdu 1181 9 the the DT cord-014597-66vd2mdu 1181 10 capsule capsule NN cord-014597-66vd2mdu 1181 11 core core NN cord-014597-66vd2mdu 1181 12 by by IN cord-014597-66vd2mdu 1181 13 autocrine autocrine JJ cord-014597-66vd2mdu 1181 14 factors factor NNS cord-014597-66vd2mdu 1181 15 , , , cord-014597-66vd2mdu 1181 16 which which WDT cord-014597-66vd2mdu 1181 17 in in IN cord-014597-66vd2mdu 1181 18 turn turn NN cord-014597-66vd2mdu 1181 19 permits permit VBZ cord-014597-66vd2mdu 1181 20 the the DT cord-014597-66vd2mdu 1181 21 use use NN cord-014597-66vd2mdu 1181 22 of of IN cord-014597-66vd2mdu 1181 23 basal basal JJ cord-014597-66vd2mdu 1181 24 cell cell NN cord-014597-66vd2mdu 1181 25 culture culture NN cord-014597-66vd2mdu 1181 26 medium medium NN cord-014597-66vd2mdu 1181 27 instead instead RB cord-014597-66vd2mdu 1181 28 of of IN cord-014597-66vd2mdu 1181 29 expensive expensive JJ cord-014597-66vd2mdu 1181 30 T t NN cord-014597-66vd2mdu 1181 31 cell cell NN cord-014597-66vd2mdu 1181 32 specialized specialized JJ cord-014597-66vd2mdu 1181 33 media medium NNS cord-014597-66vd2mdu 1181 34 , , , cord-014597-66vd2mdu 1181 35 hence hence RB cord-014597-66vd2mdu 1181 36 does do VBZ cord-014597-66vd2mdu 1181 37 not not RB cord-014597-66vd2mdu 1181 38 necessitate necessitate VB cord-014597-66vd2mdu 1181 39 high high JJ cord-014597-66vd2mdu 1181 40 amounts amount NNS cord-014597-66vd2mdu 1181 41 of of IN cord-014597-66vd2mdu 1181 42 rhIL-2 rhil-2 NN cord-014597-66vd2mdu 1181 43 and and CC cord-014597-66vd2mdu 1181 44 reduces reduce VBZ cord-014597-66vd2mdu 1181 45 the the DT cord-014597-66vd2mdu 1181 46 cultivation cultivation NN cord-014597-66vd2mdu 1181 47 costs cost NNS cord-014597-66vd2mdu 1181 48 . . . cord-014597-66vd2mdu 1182 1 Moreover moreover RB cord-014597-66vd2mdu 1182 2 , , , cord-014597-66vd2mdu 1182 3 co co NN cord-014597-66vd2mdu 1182 4 - - NN cord-014597-66vd2mdu 1182 5 encapsulation encapsulation NN cord-014597-66vd2mdu 1182 6 of of IN cord-014597-66vd2mdu 1182 7 rhIL-2 rhil-2 NN cord-014597-66vd2mdu 1182 8 had have VBD cord-014597-66vd2mdu 1182 9 a a DT cord-014597-66vd2mdu 1182 10 beneficial beneficial JJ cord-014597-66vd2mdu 1182 11 effect effect NN cord-014597-66vd2mdu 1182 12 on on IN cord-014597-66vd2mdu 1182 13 the the DT cord-014597-66vd2mdu 1182 14 growth growth NN cord-014597-66vd2mdu 1182 15 kinetics kinetic NNS cord-014597-66vd2mdu 1182 16 in in IN cord-014597-66vd2mdu 1182 17 most most JJS cord-014597-66vd2mdu 1182 18 cases case NNS cord-014597-66vd2mdu 1183 1 ( ( -LRB- cord-014597-66vd2mdu 1183 2 Fig Fig NNP cord-014597-66vd2mdu 1183 3 . . . cord-014597-66vd2mdu 1183 4 1c 1c CD cord-014597-66vd2mdu 1183 5 ) ) -RRB- cord-014597-66vd2mdu 1183 6 . . . cord-014597-66vd2mdu 1184 1 Some some DT cord-014597-66vd2mdu 1184 2 evidence evidence NN cord-014597-66vd2mdu 1184 3 is be VBZ cord-014597-66vd2mdu 1184 4 presented present VBN cord-014597-66vd2mdu 1184 5 that that IN cord-014597-66vd2mdu 1184 6 the the DT cord-014597-66vd2mdu 1184 7 SCS SCS NNP cord-014597-66vd2mdu 1184 8 used use VBD cord-014597-66vd2mdu 1184 9 to to TO cord-014597-66vd2mdu 1184 10 form form VB cord-014597-66vd2mdu 1184 11 the the DT cord-014597-66vd2mdu 1184 12 polyelectrolyte polyelectrolyte NNP cord-014597-66vd2mdu 1184 13 microcapsules microcapsules NNP cord-014597-66vd2mdu 1184 14 , , , cord-014597-66vd2mdu 1184 15 specifically specifically RB cord-014597-66vd2mdu 1184 16 adsorbs adsorb VBZ cord-014597-66vd2mdu 1184 17 IL-2 IL-2 NNP cord-014597-66vd2mdu 1184 18 ( ( -LRB- cord-014597-66vd2mdu 1184 19 Table Table NNP cord-014597-66vd2mdu 1184 20 1 1 CD cord-014597-66vd2mdu 1184 21 ) ) -RRB- cord-014597-66vd2mdu 1185 1 -A -A : cord-014597-66vd2mdu 1185 2 cytokine cytokine NN cord-014597-66vd2mdu 1185 3 which which WDT cord-014597-66vd2mdu 1185 4 provides provide VBZ cord-014597-66vd2mdu 1185 5 an an DT cord-014597-66vd2mdu 1185 6 essential essential JJ cord-014597-66vd2mdu 1185 7 signal signal NN cord-014597-66vd2mdu 1185 8 for for IN cord-014597-66vd2mdu 1185 9 T t NN cord-014597-66vd2mdu 1185 10 - - HYPH cord-014597-66vd2mdu 1185 11 cell cell NN cord-014597-66vd2mdu 1185 12 proliferation proliferation NN cord-014597-66vd2mdu 1185 13 and and CC cord-014597-66vd2mdu 1185 14 differentiation differentiation NN cord-014597-66vd2mdu 1185 15 [ [ -LRB- cord-014597-66vd2mdu 1185 16 3 3 CD cord-014597-66vd2mdu 1185 17 ] ] -RRB- cord-014597-66vd2mdu 1185 18 . . . cord-014597-66vd2mdu 1186 1 Therefore therefore RB cord-014597-66vd2mdu 1186 2 , , , cord-014597-66vd2mdu 1186 3 we -PRON- PRP cord-014597-66vd2mdu 1186 4 postulate postulate VBP cord-014597-66vd2mdu 1186 5 that that IN cord-014597-66vd2mdu 1186 6 the the DT cord-014597-66vd2mdu 1186 7 SCS SCS NNP cord-014597-66vd2mdu 1186 8 used use VBN cord-014597-66vd2mdu 1186 9 for for IN cord-014597-66vd2mdu 1186 10 encapsulation encapsulation NN cord-014597-66vd2mdu 1186 11 has have VBZ cord-014597-66vd2mdu 1186 12 biomimetic biomimetic JJ cord-014597-66vd2mdu 1186 13 properties property NNS cord-014597-66vd2mdu 1186 14 , , , cord-014597-66vd2mdu 1186 15 creating create VBG cord-014597-66vd2mdu 1186 16 an an DT cord-014597-66vd2mdu 1186 17 artificial artificial JJ cord-014597-66vd2mdu 1186 18 extracellular extracellular JJ cord-014597-66vd2mdu 1186 19 matrix matrix NN cord-014597-66vd2mdu 1186 20 mimicking mimic VBG cord-014597-66vd2mdu 1186 21 heparin heparin NN cord-014597-66vd2mdu 1186 22 sulfate sulfate NN cord-014597-66vd2mdu 1186 23 which which WDT cord-014597-66vd2mdu 1186 24 in in IN cord-014597-66vd2mdu 1186 25 turn turn NN cord-014597-66vd2mdu 1186 26 positively positively RB cord-014597-66vd2mdu 1186 27 affect affect VBP cord-014597-66vd2mdu 1186 28 T T NNP cord-014597-66vd2mdu 1186 29 cell cell NN cord-014597-66vd2mdu 1186 30 proliferation proliferation NN cord-014597-66vd2mdu 1186 31 via via IN cord-014597-66vd2mdu 1186 32 trans trans JJ cord-014597-66vd2mdu 1186 33 - - NN cord-014597-66vd2mdu 1186 34 presentation presentation NN cord-014597-66vd2mdu 1186 35 of of IN cord-014597-66vd2mdu 1186 36 IL-2 IL-2 NNP cord-014597-66vd2mdu 1186 37 ( ( -LRB- cord-014597-66vd2mdu 1186 38 Fig Fig NNP cord-014597-66vd2mdu 1186 39 . . . cord-014597-66vd2mdu 1186 40 1d 1d CD cord-014597-66vd2mdu 1186 41 ) ) -RRB- cord-014597-66vd2mdu 1187 1 [ [ -LRB- cord-014597-66vd2mdu 1187 2 4 4 CD cord-014597-66vd2mdu 1187 3 ] ] -RRB- cord-014597-66vd2mdu 1187 4 . . . cord-014597-66vd2mdu 1188 1 Primary primary JJ cord-014597-66vd2mdu 1188 2 T t NN cord-014597-66vd2mdu 1188 3 lymphocytes lymphocyte NNS cord-014597-66vd2mdu 1188 4 can can MD cord-014597-66vd2mdu 1188 5 be be VB cord-014597-66vd2mdu 1188 6 expanded expand VBN cord-014597-66vd2mdu 1188 7 under under IN cord-014597-66vd2mdu 1188 8 appropriate appropriate JJ cord-014597-66vd2mdu 1188 9 conditions condition NNS cord-014597-66vd2mdu 1188 10 outside outside IN cord-014597-66vd2mdu 1188 11 the the DT cord-014597-66vd2mdu 1188 12 body body NN cord-014597-66vd2mdu 1188 13 . . . cord-014597-66vd2mdu 1189 1 In in IN cord-014597-66vd2mdu 1189 2 the the DT cord-014597-66vd2mdu 1189 3 latter latter JJ cord-014597-66vd2mdu 1189 4 , , , cord-014597-66vd2mdu 1189 5 T t NN cord-014597-66vd2mdu 1189 6 cells cell NNS cord-014597-66vd2mdu 1189 7 grow grow VBP cord-014597-66vd2mdu 1189 8 / / SYM cord-014597-66vd2mdu 1189 9 expand expand VBP cord-014597-66vd2mdu 1189 10 in in IN cord-014597-66vd2mdu 1189 11 specific specific JJ cord-014597-66vd2mdu 1189 12 environments environment NNS cord-014597-66vd2mdu 1189 13 where where WRB cord-014597-66vd2mdu 1189 14 the the DT cord-014597-66vd2mdu 1189 15 cells cell NNS cord-014597-66vd2mdu 1189 16 are be VBP cord-014597-66vd2mdu 1189 17 tightly tightly RB cord-014597-66vd2mdu 1189 18 packed pack VBN cord-014597-66vd2mdu 1189 19 , , , cord-014597-66vd2mdu 1189 20 leading lead VBG cord-014597-66vd2mdu 1189 21 to to IN cord-014597-66vd2mdu 1189 22 multiple multiple JJ cord-014597-66vd2mdu 1189 23 cell cell NN cord-014597-66vd2mdu 1189 24 - - HYPH cord-014597-66vd2mdu 1189 25 cell cell NN cord-014597-66vd2mdu 1189 26 contacts contact NNS cord-014597-66vd2mdu 1189 27 and and CC cord-014597-66vd2mdu 1189 28 manifold manifold JJ cord-014597-66vd2mdu 1189 29 interactions interaction NNS cord-014597-66vd2mdu 1189 30 with with IN cord-014597-66vd2mdu 1189 31 the the DT cord-014597-66vd2mdu 1189 32 extracellular extracellular JJ cord-014597-66vd2mdu 1189 33 matrix matrix NN cord-014597-66vd2mdu 1189 34 . . . cord-014597-66vd2mdu 1190 1 Ex Ex NNP cord-014597-66vd2mdu 1190 2 vivo vivo NN cord-014597-66vd2mdu 1190 3 suspension suspension NN cord-014597-66vd2mdu 1190 4 cultures culture NNS cord-014597-66vd2mdu 1190 5 of of IN cord-014597-66vd2mdu 1190 6 diluted diluted JJ cord-014597-66vd2mdu 1190 7 cells cell NNS cord-014597-66vd2mdu 1190 8 can can MD cord-014597-66vd2mdu 1190 9 not not RB cord-014597-66vd2mdu 1190 10 provide provide VB cord-014597-66vd2mdu 1190 11 such such PDT cord-014597-66vd2mdu 1190 12 a a DT cord-014597-66vd2mdu 1190 13 microenvironment microenvironment NN cord-014597-66vd2mdu 1190 14 . . . cord-014597-66vd2mdu 1191 1 In in IN cord-014597-66vd2mdu 1191 2 the the DT cord-014597-66vd2mdu 1191 3 microcapsulesbased microcapsulesbased JJ cord-014597-66vd2mdu 1191 4 cultivation cultivation NN cord-014597-66vd2mdu 1191 5 system system NN cord-014597-66vd2mdu 1191 6 presented present VBN cord-014597-66vd2mdu 1191 7 , , , cord-014597-66vd2mdu 1191 8 the the DT cord-014597-66vd2mdu 1191 9 cells cell NNS cord-014597-66vd2mdu 1191 10 are be VBP cord-014597-66vd2mdu 1191 11 suspended suspend VBN cord-014597-66vd2mdu 1191 12 in in IN cord-014597-66vd2mdu 1191 13 a a DT cord-014597-66vd2mdu 1191 14 viscous viscous JJ cord-014597-66vd2mdu 1191 15 SCS scs NN cord-014597-66vd2mdu 1191 16 - - HYPH cord-014597-66vd2mdu 1191 17 solution solution NN cord-014597-66vd2mdu 1191 18 . . . cord-014597-66vd2mdu 1192 1 The the DT cord-014597-66vd2mdu 1192 2 low low JJ cord-014597-66vd2mdu 1192 3 molecular molecular JJ cord-014597-66vd2mdu 1192 4 weight weight NN cord-014597-66vd2mdu 1192 5 cut cut VBN cord-014597-66vd2mdu 1192 6 off off IN cord-014597-66vd2mdu 1192 7 of of IN cord-014597-66vd2mdu 1192 8 the the DT cord-014597-66vd2mdu 1192 9 surrounding surround VBG cord-014597-66vd2mdu 1192 10 polyelectrolyte polyelectrolyte NNP cord-014597-66vd2mdu 1192 11 membrane membrane NN cord-014597-66vd2mdu 1192 12 assures assure VBZ cord-014597-66vd2mdu 1192 13 that that IN cord-014597-66vd2mdu 1192 14 typical typical JJ cord-014597-66vd2mdu 1192 15 signaling signal VBG cord-014597-66vd2mdu 1192 16 molecules molecule NNS cord-014597-66vd2mdu 1192 17 produced produce VBN cord-014597-66vd2mdu 1192 18 by by IN cord-014597-66vd2mdu 1192 19 the the DT cord-014597-66vd2mdu 1192 20 cells cell NNS cord-014597-66vd2mdu 1192 21 are be VBP cord-014597-66vd2mdu 1192 22 retained retain VBN cord-014597-66vd2mdu 1192 23 thus thus RB cord-014597-66vd2mdu 1192 24 facilitates facilitate VBZ cord-014597-66vd2mdu 1192 25 the the DT cord-014597-66vd2mdu 1192 26 " " `` cord-014597-66vd2mdu 1192 27 conditioning conditioning NN cord-014597-66vd2mdu 1192 28 " " '' cord-014597-66vd2mdu 1192 29 of of IN cord-014597-66vd2mdu 1192 30 the the DT cord-014597-66vd2mdu 1192 31 cellular cellular JJ cord-014597-66vd2mdu 1192 32 microenvironment microenvironment NN cord-014597-66vd2mdu 1192 33 , , , cord-014597-66vd2mdu 1192 34 while while IN cord-014597-66vd2mdu 1192 35 nutrients nutrient NNS cord-014597-66vd2mdu 1192 36 and and CC cord-014597-66vd2mdu 1192 37 metabolites metabolite NNS cord-014597-66vd2mdu 1192 38 can can MD cord-014597-66vd2mdu 1192 39 pass pass VB cord-014597-66vd2mdu 1192 40 . . . cord-014597-66vd2mdu 1193 1 Expensive expensive JJ cord-014597-66vd2mdu 1193 2 additives additive NNS cord-014597-66vd2mdu 1193 3 , , , cord-014597-66vd2mdu 1193 4 such such JJ cord-014597-66vd2mdu 1193 5 as as IN cord-014597-66vd2mdu 1193 6 interleukin-2 interleukin-2 IN cord-014597-66vd2mdu 1193 7 ( ( -LRB- cord-014597-66vd2mdu 1193 8 IL-2 IL-2 NNP cord-014597-66vd2mdu 1193 9 ) ) -RRB- cord-014597-66vd2mdu 1193 10 , , , cord-014597-66vd2mdu 1193 11 can can MD cord-014597-66vd2mdu 1193 12 be be VB cord-014597-66vd2mdu 1193 13 co co VBN cord-014597-66vd2mdu 1193 14 - - VBN cord-014597-66vd2mdu 1193 15 encapsulated encapsulate VBN cord-014597-66vd2mdu 1193 16 . . . cord-014597-66vd2mdu 1194 1 Expansion expansion NN cord-014597-66vd2mdu 1194 2 then then RB cord-014597-66vd2mdu 1194 3 no no RB cord-014597-66vd2mdu 1194 4 longer longer RB cord-014597-66vd2mdu 1194 5 requires require VBZ cord-014597-66vd2mdu 1194 6 specialized specialized JJ cord-014597-66vd2mdu 1194 7 T t NN cord-014597-66vd2mdu 1194 8 - - HYPH cord-014597-66vd2mdu 1194 9 cell cell NN cord-014597-66vd2mdu 1194 10 media medium NNS cord-014597-66vd2mdu 1194 11 . . . cord-014597-66vd2mdu 1195 1 Moreover moreover RB cord-014597-66vd2mdu 1195 2 , , , cord-014597-66vd2mdu 1195 3 the the DT cord-014597-66vd2mdu 1195 4 SCS SCS NNP cord-014597-66vd2mdu 1195 5 seems seem VBZ cord-014597-66vd2mdu 1195 6 to to TO cord-014597-66vd2mdu 1195 7 have have VB cord-014597-66vd2mdu 1195 8 biomimetic biomimetic JJ cord-014597-66vd2mdu 1195 9 properties property NNS cord-014597-66vd2mdu 1195 10 , , , cord-014597-66vd2mdu 1195 11 representing represent VBG cord-014597-66vd2mdu 1195 12 an an DT cord-014597-66vd2mdu 1195 13 artificial artificial JJ cord-014597-66vd2mdu 1195 14 extracellular extracellular JJ cord-014597-66vd2mdu 1195 15 matrix matrix NN cord-014597-66vd2mdu 1195 16 mimicking mimic VBG cord-014597-66vd2mdu 1195 17 heparin heparin NN cord-014597-66vd2mdu 1195 18 sulfate sulfate NN cord-014597-66vd2mdu 1195 19 . . . cord-014597-66vd2mdu 1196 1 We -PRON- PRP cord-014597-66vd2mdu 1196 2 consider consider VBP cord-014597-66vd2mdu 1196 3 that that IN cord-014597-66vd2mdu 1196 4 the the DT cord-014597-66vd2mdu 1196 5 described describe VBN cord-014597-66vd2mdu 1196 6 method method NN cord-014597-66vd2mdu 1196 7 may may MD cord-014597-66vd2mdu 1196 8 be be VB cord-014597-66vd2mdu 1196 9 an an DT cord-014597-66vd2mdu 1196 10 appropriate appropriate JJ cord-014597-66vd2mdu 1196 11 alternative alternative NN cord-014597-66vd2mdu 1196 12 to to TO cord-014597-66vd2mdu 1196 13 expand expand VB cord-014597-66vd2mdu 1196 14 T t NN cord-014597-66vd2mdu 1196 15 cells cell NNS cord-014597-66vd2mdu 1196 16 while while IN cord-014597-66vd2mdu 1196 17 creating create VBG cord-014597-66vd2mdu 1196 18 a a DT cord-014597-66vd2mdu 1196 19 local local JJ cord-014597-66vd2mdu 1196 20 microenvironment microenvironment NN cord-014597-66vd2mdu 1196 21 mimicking mimic VBG cord-014597-66vd2mdu 1196 22 in in IN cord-014597-66vd2mdu 1196 23 vivo vivo NN cord-014597-66vd2mdu 1196 24 conditions condition NNS cord-014597-66vd2mdu 1196 25 . . . cord-014597-66vd2mdu 1197 1 -175 -175 NNP cord-014597-66vd2mdu 1197 2 ) ) -RRB- cord-014597-66vd2mdu 1197 3 . . . cord-014597-66vd2mdu 1198 1 Equations equation NNS cord-014597-66vd2mdu 1198 2 of of IN cord-014597-66vd2mdu 1198 3 balances balance NNS cord-014597-66vd2mdu 1198 4 and and CC cord-014597-66vd2mdu 1198 5 kinetics kinetic NNS cord-014597-66vd2mdu 1198 6 of of IN cord-014597-66vd2mdu 1198 7 an an DT cord-014597-66vd2mdu 1198 8 employed employ VBN cord-014597-66vd2mdu 1198 9 process process NN cord-014597-66vd2mdu 1198 10 model model NN cord-014597-66vd2mdu 1198 11 including include VBG cord-014597-66vd2mdu 1198 12 X x NN cord-014597-66vd2mdu 1198 13 v v NN cord-014597-66vd2mdu 1198 14 viable viable JJ cord-014597-66vd2mdu 1198 15 cell cell NN cord-014597-66vd2mdu 1198 16 density density NN cord-014597-66vd2mdu 1198 17 , , , cord-014597-66vd2mdu 1198 18 X X NNP cord-014597-66vd2mdu 1198 19 t t NN cord-014597-66vd2mdu 1198 20 total total JJ cord-014597-66vd2mdu 1198 21 cell cell NN cord-014597-66vd2mdu 1198 22 density density NN cord-014597-66vd2mdu 1198 23 , , , cord-014597-66vd2mdu 1198 24 μ μ NN cord-014597-66vd2mdu 1198 25 cell cell NN cord-014597-66vd2mdu 1198 26 - - HYPH cord-014597-66vd2mdu 1198 27 specific specific JJ cord-014597-66vd2mdu 1198 28 growth growth NN cord-014597-66vd2mdu 1198 29 rate rate NN cord-014597-66vd2mdu 1198 30 , , , cord-014597-66vd2mdu 1199 1 μ μ NN cord-014597-66vd2mdu 1199 2 d d NNP cord-014597-66vd2mdu 1199 3 cell cell NN cord-014597-66vd2mdu 1199 4 - - HYPH cord-014597-66vd2mdu 1199 5 specific specific JJ cord-014597-66vd2mdu 1199 6 death death NN cord-014597-66vd2mdu 1199 7 rate rate NN cord-014597-66vd2mdu 1199 8 , , , cord-014597-66vd2mdu 1199 9 t t NN cord-014597-66vd2mdu 1199 10 time time NN cord-014597-66vd2mdu 1199 11 , , , cord-014597-66vd2mdu 1199 12 K K NNP cord-014597-66vd2mdu 1199 13 S S NNP cord-014597-66vd2mdu 1199 14 and and CC cord-014597-66vd2mdu 1199 15 k k NNP cord-014597-66vd2mdu 1199 16 Monod Monod NNP cord-014597-66vd2mdu 1199 17 kinetic kinetic JJ cord-014597-66vd2mdu 1199 18 constant constant NN cord-014597-66vd2mdu 1199 19 and and CC cord-014597-66vd2mdu 1199 20 Monod Monod NNP cord-014597-66vd2mdu 1199 21 constant constant JJ cord-014597-66vd2mdu 1199 22 for for IN cord-014597-66vd2mdu 1199 23 uptake uptake NN cord-014597-66vd2mdu 1199 24 , , , cord-014597-66vd2mdu 1199 25 K K NNP cord-014597-66vd2mdu 1199 26 Lys Lys NNP cord-014597-66vd2mdu 1199 27 cell cell NN cord-014597-66vd2mdu 1199 28 lysis lysis NN cord-014597-66vd2mdu 1199 29 constant constant JJ cord-014597-66vd2mdu 1199 30 , , , cord-014597-66vd2mdu 1199 31 q q NN cord-014597-66vd2mdu 1199 32 cell cell NN cord-014597-66vd2mdu 1199 33 - - HYPH cord-014597-66vd2mdu 1199 34 specific specific JJ cord-014597-66vd2mdu 1199 35 uptake uptake NN cord-014597-66vd2mdu 1199 36 rate rate NN cord-014597-66vd2mdu 1199 37 or or CC cord-014597-66vd2mdu 1199 38 production production NN cord-014597-66vd2mdu 1199 39 rate rate NN cord-014597-66vd2mdu 1199 40 , , , cord-014597-66vd2mdu 1199 41 respectively respectively RB cord-014597-66vd2mdu 1199 42 , , , cord-014597-66vd2mdu 1199 43 Y Y NNP cord-014597-66vd2mdu 1199 44 kinetic kinetic JJ cord-014597-66vd2mdu 1199 45 production production NN cord-014597-66vd2mdu 1199 46 constant constant NN cord-014597-66vd2mdu 1199 47 , , , cord-014597-66vd2mdu 1199 48 c c NN cord-014597-66vd2mdu 1199 49 concentration concentration NN cord-014597-66vd2mdu 1199 50 , , , cord-014597-66vd2mdu 1199 51 Glc Glc NNP cord-014597-66vd2mdu 1199 52 glucose glucose NN cord-014597-66vd2mdu 1199 53 , , , cord-014597-66vd2mdu 1199 54 Gln Gln NNP cord-014597-66vd2mdu 1199 55 glutamine glutamine NN cord-014597-66vd2mdu 1199 56 , , , cord-014597-66vd2mdu 1199 57 Lac Lac NNP cord-014597-66vd2mdu 1199 58 lactate lactate NN cord-014597-66vd2mdu 1199 59 , , , cord-014597-66vd2mdu 1199 60 Amm Amm NNP cord-014597-66vd2mdu 1199 61 ammonia ammonia NN cord-014597-66vd2mdu 1199 62 , , , cord-014597-66vd2mdu 1199 63 F F NNP cord-014597-66vd2mdu 1199 64 feed feed NN cord-014597-66vd2mdu 1199 65 rate rate NN cord-014597-66vd2mdu 1199 66 , , , cord-014597-66vd2mdu 1199 67 V v NN cord-014597-66vd2mdu 1199 68 volume volume NN cord-014597-66vd2mdu 1199 69 Balances balance NNS cord-014597-66vd2mdu 1199 70 with with IN cord-014597-66vd2mdu 1199 71 fed fed NNP cord-014597-66vd2mdu 1199 72 - - HYPH cord-014597-66vd2mdu 1199 73 batch batch NN cord-014597-66vd2mdu 1199 74 terms term NNS cord-014597-66vd2mdu 1199 75 Kinetics kinetic NNS cord-014597-66vd2mdu 1199 76 ; ; : cord-014597-66vd2mdu 1199 77 uptake uptake NN cord-014597-66vd2mdu 1199 78 if if IN cord-014597-66vd2mdu 1199 79 c c NNP cord-014597-66vd2mdu 1199 80 Glc Glc NNP cord-014597-66vd2mdu 1199 81 ≥ ≥ CD cord-014597-66vd2mdu 1199 82 0.5 0.5 CD cord-014597-66vd2mdu 1199 83 mM mm NN cord-014597-66vd2mdu 1199 84 : : : cord-014597-66vd2mdu 1199 85 q q NNP cord-014597-66vd2mdu 1199 86 Lac Lac NNP cord-014597-66vd2mdu 1199 87 , , , cord-014597-66vd2mdu 1199 88 uptake uptake NN cord-014597-66vd2mdu 1199 89 = = SYM cord-014597-66vd2mdu 1199 90 0 0 NFP cord-014597-66vd2mdu 1200 1 if if IN cord-014597-66vd2mdu 1200 2 c c NNP cord-014597-66vd2mdu 1200 3 Glc Glc NNP cord-014597-66vd2mdu 1200 4 < < XX cord-014597-66vd2mdu 1200 5 0.5 0.5 CD cord-014597-66vd2mdu 1200 6 mM mm CD cord-014597-66vd2mdu 1200 7 : : : cord-014597-66vd2mdu 1200 8 q q NNP cord-014597-66vd2mdu 1200 9 Lac Lac NNP cord-014597-66vd2mdu 1200 10 , , , cord-014597-66vd2mdu 1200 11 uptake uptake NN cord-014597-66vd2mdu 1200 12 = = NN cord-014597-66vd2mdu 1200 13 q q NNP cord-014597-66vd2mdu 1200 14 Lac Lac NNP cord-014597-66vd2mdu 1200 15 , , , cord-014597-66vd2mdu 1200 16 uptake uptake NN cord-014597-66vd2mdu 1200 17 , , , cord-014597-66vd2mdu 1200 18 max max NNP cord-014597-66vd2mdu 1200 19 q q NNP cord-014597-66vd2mdu 1201 1 Amm Amm NNP cord-014597-66vd2mdu 1201 2 = = NNP cord-014597-66vd2mdu 1201 3 Y y NN cord-014597-66vd2mdu 1202 1 Amm Amm NNP cord-014597-66vd2mdu 1202 2 / / SYM cord-014597-66vd2mdu 1202 3 Gln Gln NNP cord-014597-66vd2mdu 1202 4 • • NNP cord-014597-66vd2mdu 1203 1 q q NNP cord-014597-66vd2mdu 1203 2 Gln Gln NNP cord-014597-66vd2mdu 1203 3 Background Background NNP cord-014597-66vd2mdu 1203 4 Digital Digital NNP cord-014597-66vd2mdu 1203 5 manufacturing manufacturing NN cord-014597-66vd2mdu 1203 6 ( ( -LRB- cord-014597-66vd2mdu 1203 7 DM DM NNP cord-014597-66vd2mdu 1203 8 ) ) -RRB- cord-014597-66vd2mdu 1203 9 is be VBZ cord-014597-66vd2mdu 1203 10 heightening heighten VBG cord-014597-66vd2mdu 1203 11 the the DT cord-014597-66vd2mdu 1203 12 productivity productivity NN cord-014597-66vd2mdu 1203 13 and and CC cord-014597-66vd2mdu 1203 14 robustness robustness NN cord-014597-66vd2mdu 1203 15 of of IN cord-014597-66vd2mdu 1203 16 existing exist VBG cord-014597-66vd2mdu 1203 17 processes process NNS cord-014597-66vd2mdu 1203 18 and and CC cord-014597-66vd2mdu 1203 19 facilities facility NNS cord-014597-66vd2mdu 1203 20 . . . cord-014597-66vd2mdu 1204 1 It -PRON- PRP cord-014597-66vd2mdu 1204 2 also also RB cord-014597-66vd2mdu 1204 3 enables enable VBZ cord-014597-66vd2mdu 1204 4 the the DT cord-014597-66vd2mdu 1204 5 efficient efficient JJ cord-014597-66vd2mdu 1204 6 development development NN cord-014597-66vd2mdu 1204 7 of of IN cord-014597-66vd2mdu 1204 8 previously previously RB cord-014597-66vd2mdu 1204 9 unmanageable unmanageable JJ cord-014597-66vd2mdu 1204 10 products product NNS cord-014597-66vd2mdu 1204 11 or or CC cord-014597-66vd2mdu 1204 12 processes process NNS cord-014597-66vd2mdu 1204 13 and and CC cord-014597-66vd2mdu 1204 14 provided provide VBD cord-014597-66vd2mdu 1204 15 the the DT cord-014597-66vd2mdu 1204 16 basis basis NN cord-014597-66vd2mdu 1204 17 for for IN cord-014597-66vd2mdu 1204 18 a a DT cord-014597-66vd2mdu 1204 19 wave wave NN cord-014597-66vd2mdu 1204 20 of of IN cord-014597-66vd2mdu 1204 21 innovations innovation NNS cord-014597-66vd2mdu 1204 22 . . . cord-014597-66vd2mdu 1205 1 DM DM NNP cord-014597-66vd2mdu 1205 2 is be VBZ cord-014597-66vd2mdu 1205 3 a a DT cord-014597-66vd2mdu 1205 4 resident resident NN cord-014597-66vd2mdu 1205 5 and and CC cord-014597-66vd2mdu 1205 6 on on IN cord-014597-66vd2mdu 1205 7 - - HYPH cord-014597-66vd2mdu 1205 8 line line NN cord-014597-66vd2mdu 1205 9 source source NN cord-014597-66vd2mdu 1205 10 of of IN cord-014597-66vd2mdu 1205 11 continuous continuous JJ cord-014597-66vd2mdu 1205 12 optimization optimization NN cord-014597-66vd2mdu 1205 13 of of IN cord-014597-66vd2mdu 1205 14 process process NN cord-014597-66vd2mdu 1205 15 performance performance NN cord-014597-66vd2mdu 1205 16 . . . cord-014597-66vd2mdu 1206 1 It -PRON- PRP cord-014597-66vd2mdu 1206 2 relies rely VBZ cord-014597-66vd2mdu 1206 3 upon upon IN cord-014597-66vd2mdu 1206 4 the the DT cord-014597-66vd2mdu 1206 5 comprehensive comprehensive JJ cord-014597-66vd2mdu 1206 6 , , , cord-014597-66vd2mdu 1206 7 real real JJ cord-014597-66vd2mdu 1206 8 - - HYPH cord-014597-66vd2mdu 1206 9 time time NN cord-014597-66vd2mdu 1206 10 interfacing interfacing NN cord-014597-66vd2mdu 1206 11 of of IN cord-014597-66vd2mdu 1206 12 both both DT cord-014597-66vd2mdu 1206 13 human human JJ cord-014597-66vd2mdu 1206 14 and and CC cord-014597-66vd2mdu 1206 15 machine machine NN cord-014597-66vd2mdu 1206 16 sourced source VBD cord-014597-66vd2mdu 1206 17 information information NN cord-014597-66vd2mdu 1206 18 through through IN cord-014597-66vd2mdu 1206 19 one one CD cord-014597-66vd2mdu 1206 20 centralized centralized JJ cord-014597-66vd2mdu 1206 21 system system NN cord-014597-66vd2mdu 1206 22 . . . cord-014597-66vd2mdu 1207 1 More More JJR cord-014597-66vd2mdu 1207 2 than than IN cord-014597-66vd2mdu 1207 3 legacy legacy NN cord-014597-66vd2mdu 1207 4 Distributed Distributed NNP cord-014597-66vd2mdu 1207 5 Control Control NNP cord-014597-66vd2mdu 1207 6 System System NNP cord-014597-66vd2mdu 1207 7 ( ( -LRB- cord-014597-66vd2mdu 1207 8 DCS DCS NNP cord-014597-66vd2mdu 1207 9 ) ) -RRB- cord-014597-66vd2mdu 1207 10 and and CC cord-014597-66vd2mdu 1207 11 supervisory supervisory JJ cord-014597-66vd2mdu 1207 12 control control NN cord-014597-66vd2mdu 1207 13 and and CC cord-014597-66vd2mdu 1207 14 data datum NNS cord-014597-66vd2mdu 1207 15 acquisition acquisition NN cord-014597-66vd2mdu 1207 16 ( ( -LRB- cord-014597-66vd2mdu 1207 17 SCADA SCADA NNP cord-014597-66vd2mdu 1207 18 ) ) -RRB- cord-014597-66vd2mdu 1207 19 , , , cord-014597-66vd2mdu 1207 20 it -PRON- PRP cord-014597-66vd2mdu 1207 21 is be VBZ cord-014597-66vd2mdu 1207 22 an an DT cord-014597-66vd2mdu 1207 23 integral integral JJ cord-014597-66vd2mdu 1207 24 interconnection interconnection NN cord-014597-66vd2mdu 1207 25 of of IN cord-014597-66vd2mdu 1207 26 real real JJ cord-014597-66vd2mdu 1207 27 - - HYPH cord-014597-66vd2mdu 1207 28 time time NN cord-014597-66vd2mdu 1207 29 access access NN cord-014597-66vd2mdu 1207 30 to to IN cord-014597-66vd2mdu 1207 31 divergent divergent JJ cord-014597-66vd2mdu 1207 32 sources source NNS cord-014597-66vd2mdu 1207 33 of of IN cord-014597-66vd2mdu 1207 34 information information NN cord-014597-66vd2mdu 1207 35 . . . cord-014597-66vd2mdu 1208 1 As as IN cord-014597-66vd2mdu 1208 2 such such JJ cord-014597-66vd2mdu 1208 3 , , , cord-014597-66vd2mdu 1208 4 it -PRON- PRP cord-014597-66vd2mdu 1208 5 can can MD cord-014597-66vd2mdu 1208 6 promise promise VB cord-014597-66vd2mdu 1208 7 deep deep JJ cord-014597-66vd2mdu 1208 8 analysis analysis NN cord-014597-66vd2mdu 1208 9 and and CC cord-014597-66vd2mdu 1208 10 predictions prediction NNS cord-014597-66vd2mdu 1208 11 leading lead VBG cord-014597-66vd2mdu 1208 12 to to IN cord-014597-66vd2mdu 1208 13 shortened shorten VBN cord-014597-66vd2mdu 1208 14 product product NN cord-014597-66vd2mdu 1208 15 cycle cycle NN cord-014597-66vd2mdu 1208 16 and and CC cord-014597-66vd2mdu 1208 17 advanced advanced JJ cord-014597-66vd2mdu 1208 18 process process NN cord-014597-66vd2mdu 1208 19 control control NN cord-014597-66vd2mdu 1208 20 . . . cord-014597-66vd2mdu 1209 1 This this DT cord-014597-66vd2mdu 1209 2 comprehensive comprehensive JJ cord-014597-66vd2mdu 1209 3 analysis analysis NN cord-014597-66vd2mdu 1209 4 is be VBZ cord-014597-66vd2mdu 1209 5 extending extend VBG cord-014597-66vd2mdu 1209 6 beyond beyond IN cord-014597-66vd2mdu 1209 7 operations operation NNS cord-014597-66vd2mdu 1209 8 performance performance NN cord-014597-66vd2mdu 1209 9 data datum NNS cord-014597-66vd2mdu 1209 10 from from IN cord-014597-66vd2mdu 1209 11 the the DT cord-014597-66vd2mdu 1209 12 production production NN cord-014597-66vd2mdu 1209 13 floor floor NN cord-014597-66vd2mdu 1209 14 to to IN cord-014597-66vd2mdu 1209 15 data datum NNS cord-014597-66vd2mdu 1209 16 driving drive VBG cord-014597-66vd2mdu 1209 17 such such JJ cord-014597-66vd2mdu 1209 18 activities activity NNS cord-014597-66vd2mdu 1209 19 as as IN cord-014597-66vd2mdu 1209 20 raw raw JJ cord-014597-66vd2mdu 1209 21 materials material NNS cord-014597-66vd2mdu 1209 22 security security NN cord-014597-66vd2mdu 1209 23 of of IN cord-014597-66vd2mdu 1209 24 supply supply NN cord-014597-66vd2mdu 1209 25 ( ( -LRB- cord-014597-66vd2mdu 1209 26 SoS SoS NNP cord-014597-66vd2mdu 1209 27 ) ) -RRB- cord-014597-66vd2mdu 1209 28 and and CC cord-014597-66vd2mdu 1209 29 business business NN cord-014597-66vd2mdu 1209 30 continuity continuity NN cord-014597-66vd2mdu 1209 31 management management NN cord-014597-66vd2mdu 1209 32 systems system NNS cord-014597-66vd2mdu 1209 33 ( ( -LRB- cord-014597-66vd2mdu 1209 34 BCMS BCMS NNP cord-014597-66vd2mdu 1209 35 ) ) -RRB- cord-014597-66vd2mdu 1209 36 . . . cord-014597-66vd2mdu 1210 1 Digital Digital NNP cord-014597-66vd2mdu 1210 2 Biomanufacturing Biomanufacturing NNP cord-014597-66vd2mdu 1210 3 ( ( -LRB- cord-014597-66vd2mdu 1210 4 DB DB NNP cord-014597-66vd2mdu 1210 5 ) ) -RRB- cord-014597-66vd2mdu 1210 6 can can MD cord-014597-66vd2mdu 1210 7 be be VB cord-014597-66vd2mdu 1210 8 viewed view VBN cord-014597-66vd2mdu 1210 9 as as RB cord-014597-66vd2mdu 1210 10 yet yet RB cord-014597-66vd2mdu 1210 11 another another DT cord-014597-66vd2mdu 1210 12 , , , cord-014597-66vd2mdu 1210 13 larger large JJR cord-014597-66vd2mdu 1210 14 , , , cord-014597-66vd2mdu 1210 15 embodiment embodiment NN cord-014597-66vd2mdu 1210 16 of of IN cord-014597-66vd2mdu 1210 17 digital digital JJ cord-014597-66vd2mdu 1210 18 biotechnology biotechnology NN cord-014597-66vd2mdu 1210 19 . . . cord-014597-66vd2mdu 1211 1 DB DB NNP cord-014597-66vd2mdu 1211 2 is be VBZ cord-014597-66vd2mdu 1211 3 similar similar JJ cord-014597-66vd2mdu 1211 4 to to IN cord-014597-66vd2mdu 1211 5 digital digital JJ cord-014597-66vd2mdu 1211 6 manufacturing manufacturing NN cord-014597-66vd2mdu 1211 7 in in IN cord-014597-66vd2mdu 1211 8 that that IN cord-014597-66vd2mdu 1211 9 it -PRON- PRP cord-014597-66vd2mdu 1211 10 promotes promote VBZ cord-014597-66vd2mdu 1211 11 innovations innovation NNS cord-014597-66vd2mdu 1211 12 in in IN cord-014597-66vd2mdu 1211 13 the the DT cord-014597-66vd2mdu 1211 14 manufacturing manufacturing NN cord-014597-66vd2mdu 1211 15 of of IN cord-014597-66vd2mdu 1211 16 biologicals biological NNS cord-014597-66vd2mdu 1211 17 by by IN cord-014597-66vd2mdu 1211 18 using use VBG cord-014597-66vd2mdu 1211 19 such such JJ cord-014597-66vd2mdu 1211 20 things thing NNS cord-014597-66vd2mdu 1211 21 as as IN cord-014597-66vd2mdu 1211 22 computer computer NN cord-014597-66vd2mdu 1211 23 aided aid VBD cord-014597-66vd2mdu 1211 24 design design NN cord-014597-66vd2mdu 1211 25 , , , cord-014597-66vd2mdu 1211 26 manufacture manufacture NN cord-014597-66vd2mdu 1211 27 , , , cord-014597-66vd2mdu 1211 28 verification verification NN cord-014597-66vd2mdu 1211 29 and and CC cord-014597-66vd2mdu 1211 30 deep deep JJ cord-014597-66vd2mdu 1211 31 process process NN cord-014597-66vd2mdu 1211 32 analysis analysis NN cord-014597-66vd2mdu 1211 33 using use VBG cord-014597-66vd2mdu 1211 34 software software NN cord-014597-66vd2mdu 1211 35 sensors sensor NNS cord-014597-66vd2mdu 1211 36 ( ( -LRB- cord-014597-66vd2mdu 1211 37 Fig Fig NNP cord-014597-66vd2mdu 1211 38 . . . cord-014597-66vd2mdu 1211 39 1 1 CD cord-014597-66vd2mdu 1211 40 ) ) -RRB- cord-014597-66vd2mdu 1211 41 . . . cord-014597-66vd2mdu 1212 1 However however RB cord-014597-66vd2mdu 1212 2 , , , cord-014597-66vd2mdu 1212 3 the the DT cord-014597-66vd2mdu 1212 4 fact fact NN cord-014597-66vd2mdu 1212 5 that that IN cord-014597-66vd2mdu 1212 6 there there EX cord-014597-66vd2mdu 1212 7 are be VBP cord-014597-66vd2mdu 1212 8 living live VBG cord-014597-66vd2mdu 1212 9 components component NNS cord-014597-66vd2mdu 1212 10 ( ( -LRB- cord-014597-66vd2mdu 1212 11 cells cell NNS cord-014597-66vd2mdu 1212 12 ) ) -RRB- cord-014597-66vd2mdu 1212 13 involved involve VBN cord-014597-66vd2mdu 1212 14 in in IN cord-014597-66vd2mdu 1212 15 the the DT cord-014597-66vd2mdu 1212 16 processes process NNS cord-014597-66vd2mdu 1212 17 puts put VBZ cord-014597-66vd2mdu 1212 18 a a DT cord-014597-66vd2mdu 1212 19 distinctly distinctly RB cord-014597-66vd2mdu 1212 20 different different JJ cord-014597-66vd2mdu 1212 21 flavor flavor NN cord-014597-66vd2mdu 1212 22 to to IN cord-014597-66vd2mdu 1212 23 the the DT cord-014597-66vd2mdu 1212 24 systems system NNS cord-014597-66vd2mdu 1212 25 employed employ VBN cord-014597-66vd2mdu 1212 26 . . . cord-014597-66vd2mdu 1213 1 It -PRON- PRP cord-014597-66vd2mdu 1213 2 is be VBZ cord-014597-66vd2mdu 1213 3 desirable desirable JJ cord-014597-66vd2mdu 1213 4 to to TO cord-014597-66vd2mdu 1213 5 use use VB cord-014597-66vd2mdu 1213 6 a a DT cord-014597-66vd2mdu 1213 7 distinct distinct JJ cord-014597-66vd2mdu 1213 8 term term NN cord-014597-66vd2mdu 1213 9 here here RB cord-014597-66vd2mdu 1213 10 to to TO cord-014597-66vd2mdu 1213 11 distinguish distinguish VB cord-014597-66vd2mdu 1213 12 it -PRON- PRP cord-014597-66vd2mdu 1213 13 because because IN cord-014597-66vd2mdu 1213 14 , , , cord-014597-66vd2mdu 1213 15 as as IN cord-014597-66vd2mdu 1213 16 in in IN cord-014597-66vd2mdu 1213 17 the the DT cord-014597-66vd2mdu 1213 18 terms term NNS cord-014597-66vd2mdu 1213 19 bioproduction bioproduction NN cord-014597-66vd2mdu 1213 20 and and CC cord-014597-66vd2mdu 1213 21 biopharmacology biopharmacology NN cord-014597-66vd2mdu 1213 22 , , , cord-014597-66vd2mdu 1213 23 DB DB NNP cord-014597-66vd2mdu 1213 24 addresses address VBZ cord-014597-66vd2mdu 1213 25 many many JJ cord-014597-66vd2mdu 1213 26 unique unique JJ cord-014597-66vd2mdu 1213 27 aspects aspect NNS cord-014597-66vd2mdu 1213 28 of of IN cord-014597-66vd2mdu 1213 29 biologically biologically RB cord-014597-66vd2mdu 1213 30 - - HYPH cord-014597-66vd2mdu 1213 31 based base VBN cord-014597-66vd2mdu 1213 32 activities activity NNS cord-014597-66vd2mdu 1213 33 . . . cord-014597-66vd2mdu 1214 1 The the DT cord-014597-66vd2mdu 1214 2 reasons reason NNS cord-014597-66vd2mdu 1214 3 why why WRB cord-014597-66vd2mdu 1214 4 the the DT cord-014597-66vd2mdu 1214 5 biotech biotech NN cord-014597-66vd2mdu 1214 6 and and CC cord-014597-66vd2mdu 1214 7 biopharma biopharma NN cord-014597-66vd2mdu 1214 8 industry industry NN cord-014597-66vd2mdu 1214 9 lags lag VBZ cord-014597-66vd2mdu 1214 10 behind behind IN cord-014597-66vd2mdu 1214 11 other other JJ cord-014597-66vd2mdu 1214 12 sectors sector NNS cord-014597-66vd2mdu 1214 13 such such JJ cord-014597-66vd2mdu 1214 14 as as IN cord-014597-66vd2mdu 1214 15 the the DT cord-014597-66vd2mdu 1214 16 automotive automotive NN cord-014597-66vd2mdu 1214 17 regarding regard VBG cord-014597-66vd2mdu 1214 18 the the DT cord-014597-66vd2mdu 1214 19 transformation transformation NN cord-014597-66vd2mdu 1214 20 to to IN cord-014597-66vd2mdu 1214 21 digital digital JJ cord-014597-66vd2mdu 1214 22 manufacturing manufacturing NN cord-014597-66vd2mdu 1214 23 are be VBP cord-014597-66vd2mdu 1214 24 ( ( -LRB- cord-014597-66vd2mdu 1214 25 i i NN cord-014597-66vd2mdu 1214 26 ) ) -RRB- cord-014597-66vd2mdu 1215 1 the the DT cord-014597-66vd2mdu 1215 2 complexity complexity NN cord-014597-66vd2mdu 1215 3 and and CC cord-014597-66vd2mdu 1215 4 dissipative dissipative JJ cord-014597-66vd2mdu 1215 5 nature nature NN cord-014597-66vd2mdu 1215 6 of of IN cord-014597-66vd2mdu 1215 7 biological biological JJ cord-014597-66vd2mdu 1215 8 systems system NNS cord-014597-66vd2mdu 1215 9 , , , cord-014597-66vd2mdu 1215 10 ( ( -LRB- cord-014597-66vd2mdu 1215 11 ii ii NN cord-014597-66vd2mdu 1215 12 ) ) -RRB- cord-014597-66vd2mdu 1215 13 distributed distribute VBD cord-014597-66vd2mdu 1215 14 heterogeneous heterogeneous JJ cord-014597-66vd2mdu 1215 15 data datum NNS cord-014597-66vd2mdu 1215 16 and and CC cord-014597-66vd2mdu 1215 17 ( ( -LRB- cord-014597-66vd2mdu 1215 18 iii iii NN cord-014597-66vd2mdu 1215 19 ) ) -RRB- cord-014597-66vd2mdu 1215 20 limited limit VBN cord-014597-66vd2mdu 1215 21 at at IN cord-014597-66vd2mdu 1215 22 - - HYPH cord-014597-66vd2mdu 1215 23 line line NN cord-014597-66vd2mdu 1215 24 or or CC cord-014597-66vd2mdu 1215 25 on on IN cord-014597-66vd2mdu 1215 26 - - HYPH cord-014597-66vd2mdu 1215 27 line line NN cord-014597-66vd2mdu 1215 28 data datum NNS cord-014597-66vd2mdu 1215 29 sources source NNS cord-014597-66vd2mdu 1215 30 . . . cord-014597-66vd2mdu 1216 1 However however RB cord-014597-66vd2mdu 1216 2 , , , cord-014597-66vd2mdu 1216 3 the the DT cord-014597-66vd2mdu 1216 4 costs cost NNS cord-014597-66vd2mdu 1216 5 of of IN cord-014597-66vd2mdu 1216 6 genomic genomic JJ cord-014597-66vd2mdu 1216 7 sequencing sequencing NN cord-014597-66vd2mdu 1216 8 , , , cord-014597-66vd2mdu 1216 9 omics omics NNP cord-014597-66vd2mdu 1216 10 data data NN cord-014597-66vd2mdu 1216 11 generation generation NN cord-014597-66vd2mdu 1216 12 , , , cord-014597-66vd2mdu 1216 13 and and CC cord-014597-66vd2mdu 1216 14 computing computing NN cord-014597-66vd2mdu 1216 15 resources resource NNS cord-014597-66vd2mdu 1216 16 are be VBP cord-014597-66vd2mdu 1216 17 decreasing decrease VBG cord-014597-66vd2mdu 1216 18 rapidly rapidly RB cord-014597-66vd2mdu 1216 19 , , , cord-014597-66vd2mdu 1216 20 and and CC cord-014597-66vd2mdu 1216 21 at at IN cord-014597-66vd2mdu 1216 22 the the DT cord-014597-66vd2mdu 1216 23 same same JJ cord-014597-66vd2mdu 1216 24 time time NN cord-014597-66vd2mdu 1216 25 process process NN cord-014597-66vd2mdu 1216 26 analytical analytical JJ cord-014597-66vd2mdu 1216 27 technologies technology NNS cord-014597-66vd2mdu 1216 28 , , , cord-014597-66vd2mdu 1216 29 computational computational JJ cord-014597-66vd2mdu 1216 30 power power NN cord-014597-66vd2mdu 1216 31 and and CC cord-014597-66vd2mdu 1216 32 predictive predictive JJ cord-014597-66vd2mdu 1216 33 modeling modeling NN cord-014597-66vd2mdu 1216 34 as as RB cord-014597-66vd2mdu 1216 35 well well RB cord-014597-66vd2mdu 1216 36 as as IN cord-014597-66vd2mdu 1216 37 data datum NNS cord-014597-66vd2mdu 1216 38 management management NN cord-014597-66vd2mdu 1216 39 infrastructures infrastructure NNS cord-014597-66vd2mdu 1216 40 are be VBP cord-014597-66vd2mdu 1216 41 greatly greatly RB cord-014597-66vd2mdu 1216 42 improving improve VBG cord-014597-66vd2mdu 1216 43 ( ( -LRB- cord-014597-66vd2mdu 1216 44 Table table NN cord-014597-66vd2mdu 1216 45 1 1 CD cord-014597-66vd2mdu 1216 46 ) ) -RRB- cord-014597-66vd2mdu 1216 47 . . . cord-014597-66vd2mdu 1217 1 By by IN cord-014597-66vd2mdu 1217 2 removing remove VBG cord-014597-66vd2mdu 1217 3 roadblocks roadblock NNS cord-014597-66vd2mdu 1217 4 that that WDT cord-014597-66vd2mdu 1217 5 used use VBD cord-014597-66vd2mdu 1217 6 to to TO cord-014597-66vd2mdu 1217 7 limit limit VB cord-014597-66vd2mdu 1217 8 approaches approach NNS cord-014597-66vd2mdu 1217 9 , , , cord-014597-66vd2mdu 1217 10 these these DT cord-014597-66vd2mdu 1217 11 changes change NNS cord-014597-66vd2mdu 1217 12 have have VBP cord-014597-66vd2mdu 1217 13 paved pave VBN cord-014597-66vd2mdu 1217 14 the the DT cord-014597-66vd2mdu 1217 15 way way NN cord-014597-66vd2mdu 1217 16 to to IN cord-014597-66vd2mdu 1217 17 transforming transform VBG cord-014597-66vd2mdu 1217 18 the the DT cord-014597-66vd2mdu 1217 19 bioeconomy bioeconomy NN cord-014597-66vd2mdu 1217 20 into into IN cord-014597-66vd2mdu 1217 21 an an DT cord-014597-66vd2mdu 1217 22 industry industry NN cord-014597-66vd2mdu 1217 23 that that WDT cord-014597-66vd2mdu 1217 24 is be VBZ cord-014597-66vd2mdu 1217 25 based base VBN cord-014597-66vd2mdu 1217 26 on on IN cord-014597-66vd2mdu 1217 27 digital digital JJ cord-014597-66vd2mdu 1217 28 knowledge knowledge NN cord-014597-66vd2mdu 1217 29 . . . cord-014597-66vd2mdu 1218 1 Such such JJ cord-014597-66vd2mdu 1218 2 new new JJ cord-014597-66vd2mdu 1218 3 and and CC cord-014597-66vd2mdu 1218 4 optimized optimize VBN cord-014597-66vd2mdu 1218 5 manufacturing manufacturing NN cord-014597-66vd2mdu 1218 6 technologies technology NNS cord-014597-66vd2mdu 1218 7 as as IN cord-014597-66vd2mdu 1218 8 continuous continuous JJ cord-014597-66vd2mdu 1218 9 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 1218 10 and and CC cord-014597-66vd2mdu 1218 11 3D 3D NNP cord-014597-66vd2mdu 1218 12 bioprinting bioprinting NN cord-014597-66vd2mdu 1218 13 can can MD cord-014597-66vd2mdu 1218 14 actually actually RB cord-014597-66vd2mdu 1218 15 demand demand VB cord-014597-66vd2mdu 1218 16 the the DT cord-014597-66vd2mdu 1218 17 interfacing interfacing NN cord-014597-66vd2mdu 1218 18 of of IN cord-014597-66vd2mdu 1218 19 many many JJ cord-014597-66vd2mdu 1218 20 sources source NNS cord-014597-66vd2mdu 1218 21 of of IN cord-014597-66vd2mdu 1218 22 information information NN cord-014597-66vd2mdu 1218 23 , , , cord-014597-66vd2mdu 1218 24 deep deep JJ cord-014597-66vd2mdu 1218 25 data datum NNS cord-014597-66vd2mdu 1218 26 Prior prior RB cord-014597-66vd2mdu 1218 27 to to IN cord-014597-66vd2mdu 1218 28 ELISA ELISA NNP cord-014597-66vd2mdu 1218 29 , , , cord-014597-66vd2mdu 1218 30 the the DT cord-014597-66vd2mdu 1218 31 various various JJ cord-014597-66vd2mdu 1218 32 proteins protein NNS cord-014597-66vd2mdu 1218 33 were be VBD cord-014597-66vd2mdu 1218 34 incubated incubate VBN cord-014597-66vd2mdu 1218 35 at at IN cord-014597-66vd2mdu 1218 36 37 37 CD cord-014597-66vd2mdu 1218 37 ° ° NN cord-014597-66vd2mdu 1218 38 C c NN cord-014597-66vd2mdu 1218 39 in in IN cord-014597-66vd2mdu 1218 40 SCS SCS NNP cord-014597-66vd2mdu 1218 41 prepared prepare VBD cord-014597-66vd2mdu 1218 42 as as IN cord-014597-66vd2mdu 1218 43 for for IN cord-014597-66vd2mdu 1218 44 encapsulation encapsulation NN cord-014597-66vd2mdu 1218 45 . . . cord-014597-66vd2mdu 1219 1 As as IN cord-014597-66vd2mdu 1219 2 control control NN cord-014597-66vd2mdu 1219 3 , , , cord-014597-66vd2mdu 1219 4 the the DT cord-014597-66vd2mdu 1219 5 SCS SCS NNP cord-014597-66vd2mdu 1219 6 was be VBD cord-014597-66vd2mdu 1219 7 replaced replace VBN cord-014597-66vd2mdu 1219 8 by by IN cord-014597-66vd2mdu 1219 9 PBS PBS NNP cord-014597-66vd2mdu 1219 10 . . . cord-014597-66vd2mdu 1220 1 Shown show VBN cord-014597-66vd2mdu 1220 2 are be VBP cord-014597-66vd2mdu 1220 3 mean mean JJ cord-014597-66vd2mdu 1220 4 values value NNS cord-014597-66vd2mdu 1220 5 ± ± NNP cord-014597-66vd2mdu 1220 6 SD SD NNP cord-014597-66vd2mdu 1220 7 , , , cord-014597-66vd2mdu 1220 8 n n NN cord-014597-66vd2mdu 1220 9 = = SYM cord-014597-66vd2mdu 1220 10 3 3 CD cord-014597-66vd2mdu 1220 11 analysis analysis NN cord-014597-66vd2mdu 1220 12 including include VBG cord-014597-66vd2mdu 1220 13 software software NN cord-014597-66vd2mdu 1220 14 sensors sensor NNS cord-014597-66vd2mdu 1220 15 for for IN cord-014597-66vd2mdu 1220 16 metabolic metabolic JJ cord-014597-66vd2mdu 1220 17 fluxes flux NNS cord-014597-66vd2mdu 1220 18 , , , cord-014597-66vd2mdu 1220 19 and and CC cord-014597-66vd2mdu 1220 20 model model NN cord-014597-66vd2mdu 1220 21 - - HYPH cord-014597-66vd2mdu 1220 22 based base VBN cord-014597-66vd2mdu 1220 23 predictions prediction NNS cord-014597-66vd2mdu 1220 24 of of IN cord-014597-66vd2mdu 1220 25 digital digital JJ cord-014597-66vd2mdu 1220 26 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 1220 27 . . . cord-014597-66vd2mdu 1221 1 The the DT cord-014597-66vd2mdu 1221 2 application application NN cord-014597-66vd2mdu 1221 3 of of IN cord-014597-66vd2mdu 1221 4 predictive predictive JJ cord-014597-66vd2mdu 1221 5 models model NNS cord-014597-66vd2mdu 1221 6 for for IN cord-014597-66vd2mdu 1221 7 bioprocess bioprocess NN cord-014597-66vd2mdu 1221 8 optimization optimization NN cord-014597-66vd2mdu 1221 9 greatly greatly RB cord-014597-66vd2mdu 1221 10 improves improve VBZ cord-014597-66vd2mdu 1221 11 established establish VBN cord-014597-66vd2mdu 1221 12 platforms platform NNS cord-014597-66vd2mdu 1221 13 and and CC cord-014597-66vd2mdu 1221 14 finally finally RB cord-014597-66vd2mdu 1221 15 leads lead VBZ cord-014597-66vd2mdu 1221 16 to to IN cord-014597-66vd2mdu 1221 17 a a DT cord-014597-66vd2mdu 1221 18 massively massively RB cord-014597-66vd2mdu 1221 19 increased increase VBN cord-014597-66vd2mdu 1221 20 mechanistic mechanistic JJ cord-014597-66vd2mdu 1221 21 process process NN cord-014597-66vd2mdu 1221 22 understanding understanding NN cord-014597-66vd2mdu 1221 23 . . . cord-014597-66vd2mdu 1222 1 Four four CD cord-014597-66vd2mdu 1222 2 essential essential JJ cord-014597-66vd2mdu 1222 3 benefits benefit NNS cord-014597-66vd2mdu 1222 4 result result VBP cord-014597-66vd2mdu 1222 5 from from IN cord-014597-66vd2mdu 1222 6 the the DT cord-014597-66vd2mdu 1222 7 increased increase VBN cord-014597-66vd2mdu 1222 8 bioprocess bioprocess NN cord-014597-66vd2mdu 1222 9 understanding understanding NN cord-014597-66vd2mdu 1222 10 , , , cord-014597-66vd2mdu 1222 11 development development NN cord-014597-66vd2mdu 1222 12 , , , cord-014597-66vd2mdu 1222 13 and and CC cord-014597-66vd2mdu 1222 14 control control NN cord-014597-66vd2mdu 1222 15 of of IN cord-014597-66vd2mdu 1222 16 DB DB NNP cord-014597-66vd2mdu 1222 17 . . . cord-014597-66vd2mdu 1223 1 First first RB cord-014597-66vd2mdu 1223 2 , , , cord-014597-66vd2mdu 1223 3 personnel personnel NNS cord-014597-66vd2mdu 1223 4 are be VBP cord-014597-66vd2mdu 1223 5 relieved relieve VBN cord-014597-66vd2mdu 1223 6 of of IN cord-014597-66vd2mdu 1223 7 many many JJ cord-014597-66vd2mdu 1223 8 manual manual JJ cord-014597-66vd2mdu 1223 9 and and CC cord-014597-66vd2mdu 1223 10 repetitive repetitive JJ cord-014597-66vd2mdu 1223 11 tasks task NNS cord-014597-66vd2mdu 1223 12 . . . cord-014597-66vd2mdu 1224 1 Second second JJ cord-014597-66vd2mdu 1224 2 , , , cord-014597-66vd2mdu 1224 3 strategic strategic JJ cord-014597-66vd2mdu 1224 4 planning planning NN cord-014597-66vd2mdu 1224 5 and and CC cord-014597-66vd2mdu 1224 6 operational operational JJ cord-014597-66vd2mdu 1224 7 efficiency efficiency NN cord-014597-66vd2mdu 1224 8 are be VBP cord-014597-66vd2mdu 1224 9 improved improve VBN cord-014597-66vd2mdu 1224 10 . . . cord-014597-66vd2mdu 1225 1 Third third RB cord-014597-66vd2mdu 1225 2 , , , cord-014597-66vd2mdu 1225 3 we -PRON- PRP cord-014597-66vd2mdu 1225 4 see see VBP cord-014597-66vd2mdu 1225 5 real real JJ cord-014597-66vd2mdu 1225 6 - - HYPH cord-014597-66vd2mdu 1225 7 time time NN cord-014597-66vd2mdu 1225 8 optimization optimization NN cord-014597-66vd2mdu 1225 9 of of IN cord-014597-66vd2mdu 1225 10 end end NN cord-014597-66vd2mdu 1225 11 - - HYPH cord-014597-66vd2mdu 1225 12 to to IN cord-014597-66vd2mdu 1225 13 - - HYPH cord-014597-66vd2mdu 1225 14 end end NN cord-014597-66vd2mdu 1225 15 manufacturing manufacturing NN cord-014597-66vd2mdu 1225 16 based base VBN cord-014597-66vd2mdu 1225 17 on on IN cord-014597-66vd2mdu 1225 18 such such JJ cord-014597-66vd2mdu 1225 19 high high JJ cord-014597-66vd2mdu 1225 20 - - HYPH cord-014597-66vd2mdu 1225 21 value value NN cord-014597-66vd2mdu 1225 22 criteria criterion NNS cord-014597-66vd2mdu 1225 23 as as IN cord-014597-66vd2mdu 1225 24 projected project VBN cord-014597-66vd2mdu 1225 25 product product NN cord-014597-66vd2mdu 1225 26 quality quality NN cord-014597-66vd2mdu 1225 27 and and CC cord-014597-66vd2mdu 1225 28 profitability profitability NN cord-014597-66vd2mdu 1225 29 . . . cord-014597-66vd2mdu 1226 1 Fourth fourth RB cord-014597-66vd2mdu 1226 2 , , , cord-014597-66vd2mdu 1226 3 it -PRON- PRP cord-014597-66vd2mdu 1226 4 enables enable VBZ cord-014597-66vd2mdu 1226 5 previously previously RB cord-014597-66vd2mdu 1226 6 unmanageable unmanageable JJ cord-014597-66vd2mdu 1226 7 operations operation NNS cord-014597-66vd2mdu 1226 8 and and CC cord-014597-66vd2mdu 1226 9 creates create VBZ cord-014597-66vd2mdu 1226 10 innovative innovative JJ cord-014597-66vd2mdu 1226 11 solutions solution NNS cord-014597-66vd2mdu 1226 12 . . . cord-014597-66vd2mdu 1227 1 Monitoring monitor VBG cord-014597-66vd2mdu 1227 2 between between IN cord-014597-66vd2mdu 1227 3 - - HYPH cord-014597-66vd2mdu 1227 4 batch batch NN cord-014597-66vd2mdu 1227 5 behavior behavior NN cord-014597-66vd2mdu 1227 6 of of IN cord-014597-66vd2mdu 1227 7 real real JJ cord-014597-66vd2mdu 1227 8 - - HYPH cord-014597-66vd2mdu 1227 9 time time NN cord-014597-66vd2mdu 1227 10 adjusted adjust VBN cord-014597-66vd2mdu 1227 11 cellculture cellculture NN cord-014597-66vd2mdu 1227 12 parameters parameter NNS cord-014597-66vd2mdu 1227 13 Xavier Xavier NNP cord-014597-66vd2mdu 1227 14 Lories Lories NNP cord-014597-66vd2mdu 1227 15 , , , cord-014597-66vd2mdu 1227 16 Jean Jean NNP cord-014597-66vd2mdu 1227 17 - - HYPH cord-014597-66vd2mdu 1227 18 François François NNP cord-014597-66vd2mdu 1227 19 Michiels Michiels NNP cord-014597-66vd2mdu 1227 20 Arlenda Arlenda NNP cord-014597-66vd2mdu 1227 21 , , , cord-014597-66vd2mdu 1227 22 Mont Mont NNP cord-014597-66vd2mdu 1227 23 - - HYPH cord-014597-66vd2mdu 1227 24 Saint Saint NNP cord-014597-66vd2mdu 1227 25 - - HYPH cord-014597-66vd2mdu 1227 26 Guibert Guibert NNP cord-014597-66vd2mdu 1227 27 , , , cord-014597-66vd2mdu 1227 28 1435 1435 CD cord-014597-66vd2mdu 1227 29 , , , cord-014597-66vd2mdu 1227 30 Belgium Belgium NNP cord-014597-66vd2mdu 1227 31 Correspondence Correspondence NNP cord-014597-66vd2mdu 1227 32 : : : cord-014597-66vd2mdu 1228 1 Xavier Xavier NNP cord-014597-66vd2mdu 1228 2 Lories Lories NNP cord-014597-66vd2mdu 1228 3 ( ( -LRB- cord-014597-66vd2mdu 1228 4 xavier.lories@arlenda.com xavier.lories@arlenda.com ADD cord-014597-66vd2mdu 1228 5 ) ) -RRB- cord-014597-66vd2mdu 1229 1 BMC BMC NNP cord-014597-66vd2mdu 1229 2 Proceedings Proceedings NNP cord-014597-66vd2mdu 1229 3 2018 2018 CD cord-014597-66vd2mdu 1229 4 , , , cord-014597-66vd2mdu 1230 1 12(Suppl 12(suppl CD cord-014597-66vd2mdu 1230 2 1):P-192 1):p-192 CD cord-014597-66vd2mdu 1231 1 Background Background NNP cord-014597-66vd2mdu 1231 2 Cell cell NN cord-014597-66vd2mdu 1231 3 - - HYPH cord-014597-66vd2mdu 1231 4 culture culture NN cord-014597-66vd2mdu 1231 5 parameters parameter NNS cord-014597-66vd2mdu 1231 6 ( ( -LRB- cord-014597-66vd2mdu 1231 7 CCP CCP NNP cord-014597-66vd2mdu 1231 8 ) ) -RRB- cord-014597-66vd2mdu 1231 9 , , , cord-014597-66vd2mdu 1231 10 such such JJ cord-014597-66vd2mdu 1231 11 as as IN cord-014597-66vd2mdu 1231 12 pH pH NNP cord-014597-66vd2mdu 1231 13 , , , cord-014597-66vd2mdu 1231 14 may may MD cord-014597-66vd2mdu 1231 15 be be VB cord-014597-66vd2mdu 1231 16 continuously continuously RB cord-014597-66vd2mdu 1231 17 measured measure VBN cord-014597-66vd2mdu 1231 18 online online RB cord-014597-66vd2mdu 1231 19 and and CC cord-014597-66vd2mdu 1231 20 subject subject JJ cord-014597-66vd2mdu 1231 21 to to IN cord-014597-66vd2mdu 1231 22 real real JJ cord-014597-66vd2mdu 1231 23 - - HYPH cord-014597-66vd2mdu 1231 24 time time NN cord-014597-66vd2mdu 1231 25 automated automated JJ cord-014597-66vd2mdu 1231 26 adjustment adjustment NN cord-014597-66vd2mdu 1231 27 ( ( -LRB- cord-014597-66vd2mdu 1231 28 e.g. e.g. RB cord-014597-66vd2mdu 1231 29 automated automate VBN cord-014597-66vd2mdu 1231 30 addition addition NN cord-014597-66vd2mdu 1231 31 of of IN cord-014597-66vd2mdu 1231 32 a a DT cord-014597-66vd2mdu 1231 33 base base NN cord-014597-66vd2mdu 1231 34 to to TO cord-014597-66vd2mdu 1231 35 prevent prevent VB cord-014597-66vd2mdu 1231 36 the the DT cord-014597-66vd2mdu 1231 37 pH pH NNP cord-014597-66vd2mdu 1231 38 to to TO cord-014597-66vd2mdu 1231 39 drop drop VB cord-014597-66vd2mdu 1231 40 too too RB cord-014597-66vd2mdu 1231 41 low low JJ cord-014597-66vd2mdu 1231 42 ) ) -RRB- cord-014597-66vd2mdu 1231 43 . . . cord-014597-66vd2mdu 1232 1 This this DT cord-014597-66vd2mdu 1232 2 is be VBZ cord-014597-66vd2mdu 1232 3 an an DT cord-014597-66vd2mdu 1232 4 efficient efficient JJ cord-014597-66vd2mdu 1232 5 method method NN cord-014597-66vd2mdu 1232 6 to to TO cord-014597-66vd2mdu 1232 7 maintain maintain VB cord-014597-66vd2mdu 1232 8 the the DT cord-014597-66vd2mdu 1232 9 parameter parameter NN cord-014597-66vd2mdu 1232 10 within within IN cord-014597-66vd2mdu 1232 11 specified specified JJ cord-014597-66vd2mdu 1232 12 limits limit NNS cord-014597-66vd2mdu 1232 13 . . . cord-014597-66vd2mdu 1233 1 This this DT cord-014597-66vd2mdu 1233 2 type type NN cord-014597-66vd2mdu 1233 3 of of IN cord-014597-66vd2mdu 1233 4 control control NN cord-014597-66vd2mdu 1233 5 constraint constraint NN cord-014597-66vd2mdu 1233 6 the the DT cord-014597-66vd2mdu 1233 7 variability variability NN cord-014597-66vd2mdu 1233 8 within within IN cord-014597-66vd2mdu 1233 9 the the DT cord-014597-66vd2mdu 1233 10 predefined predefined JJ cord-014597-66vd2mdu 1233 11 limits limit NNS cord-014597-66vd2mdu 1233 12 and and CC cord-014597-66vd2mdu 1233 13 does do VBZ cord-014597-66vd2mdu 1233 14 not not RB cord-014597-66vd2mdu 1233 15 provide provide VB cord-014597-66vd2mdu 1233 16 any any DT cord-014597-66vd2mdu 1233 17 information information NN cord-014597-66vd2mdu 1233 18 on on IN cord-014597-66vd2mdu 1233 19 the the DT cord-014597-66vd2mdu 1233 20 between between IN cord-014597-66vd2mdu 1233 21 - - HYPH cord-014597-66vd2mdu 1233 22 batch batch NN cord-014597-66vd2mdu 1233 23 variability variability NN cord-014597-66vd2mdu 1233 24 of of IN cord-014597-66vd2mdu 1233 25 the the DT cord-014597-66vd2mdu 1233 26 process process NN cord-014597-66vd2mdu 1233 27 . . . cord-014597-66vd2mdu 1234 1 Online online JJ cord-014597-66vd2mdu 1234 2 measurements measurement NNS cord-014597-66vd2mdu 1234 3 of of IN cord-014597-66vd2mdu 1234 4 CCP CCP NNP cord-014597-66vd2mdu 1234 5 provide provide VB cord-014597-66vd2mdu 1234 6 time time NN cord-014597-66vd2mdu 1234 7 - - HYPH cord-014597-66vd2mdu 1234 8 dependent dependent JJ cord-014597-66vd2mdu 1234 9 curves curve NNS cord-014597-66vd2mdu 1234 10 presenting present VBG cord-014597-66vd2mdu 1234 11 one one CD cord-014597-66vd2mdu 1234 12 or or CC cord-014597-66vd2mdu 1234 13 more more JJR cord-014597-66vd2mdu 1234 14 transitions transition NNS cord-014597-66vd2mdu 1234 15 . . . cord-014597-66vd2mdu 1235 1 Different different JJ cord-014597-66vd2mdu 1235 2 types type NNS cord-014597-66vd2mdu 1235 3 of of IN cord-014597-66vd2mdu 1235 4 transition transition NN cord-014597-66vd2mdu 1235 5 can can MD cord-014597-66vd2mdu 1235 6 be be VB cord-014597-66vd2mdu 1235 7 observed observe VBN cord-014597-66vd2mdu 1235 8 : : : cord-014597-66vd2mdu 1235 9 -The -the DT cord-014597-66vd2mdu 1235 10 process process NN cord-014597-66vd2mdu 1235 11 can can MD cord-014597-66vd2mdu 1235 12 shift shift VB cord-014597-66vd2mdu 1235 13 from from IN cord-014597-66vd2mdu 1235 14 a a DT cord-014597-66vd2mdu 1235 15 state state NN cord-014597-66vd2mdu 1235 16 in in IN cord-014597-66vd2mdu 1235 17 which which WDT cord-014597-66vd2mdu 1235 18 adjustment adjustment NN cord-014597-66vd2mdu 1235 19 is be VBZ cord-014597-66vd2mdu 1235 20 needed need VBN cord-014597-66vd2mdu 1235 21 to to TO cord-014597-66vd2mdu 1235 22 keep keep VB cord-014597-66vd2mdu 1235 23 the the DT cord-014597-66vd2mdu 1235 24 CCP CCP NNP cord-014597-66vd2mdu 1235 25 in in IN cord-014597-66vd2mdu 1235 26 range range NN cord-014597-66vd2mdu 1235 27 to to IN cord-014597-66vd2mdu 1235 28 a a DT cord-014597-66vd2mdu 1235 29 state state NN cord-014597-66vd2mdu 1235 30 in in IN cord-014597-66vd2mdu 1235 31 which which WDT cord-014597-66vd2mdu 1235 32 it -PRON- PRP cord-014597-66vd2mdu 1235 33 is be VBZ cord-014597-66vd2mdu 1235 34 not not RB cord-014597-66vd2mdu 1235 35 . . . cord-014597-66vd2mdu 1236 1 Typically typically RB cord-014597-66vd2mdu 1236 2 , , , cord-014597-66vd2mdu 1236 3 the the DT cord-014597-66vd2mdu 1236 4 CCP CCP NNP cord-014597-66vd2mdu 1236 5 drifts drift VBZ cord-014597-66vd2mdu 1236 6 away away RB cord-014597-66vd2mdu 1236 7 from from IN cord-014597-66vd2mdu 1236 8 a a DT cord-014597-66vd2mdu 1236 9 limit limit NN cord-014597-66vd2mdu 1236 10 . . . cord-014597-66vd2mdu 1237 1 -The -the DT cord-014597-66vd2mdu 1237 2 process process NN cord-014597-66vd2mdu 1237 3 shifts shift VBZ cord-014597-66vd2mdu 1237 4 from from IN cord-014597-66vd2mdu 1237 5 a a DT cord-014597-66vd2mdu 1237 6 state state NN cord-014597-66vd2mdu 1237 7 in in IN cord-014597-66vd2mdu 1237 8 which which WDT cord-014597-66vd2mdu 1237 9 adjustment adjustment NN cord-014597-66vd2mdu 1237 10 is be VBZ cord-014597-66vd2mdu 1237 11 not not RB cord-014597-66vd2mdu 1237 12 needed need VBN cord-014597-66vd2mdu 1237 13 to to IN cord-014597-66vd2mdu 1237 14 one one CD cord-014597-66vd2mdu 1237 15 in in IN cord-014597-66vd2mdu 1237 16 which which WDT cord-014597-66vd2mdu 1237 17 it -PRON- PRP cord-014597-66vd2mdu 1237 18 is be VBZ cord-014597-66vd2mdu 1237 19 . . . cord-014597-66vd2mdu 1238 1 For for IN cord-014597-66vd2mdu 1238 2 instance instance NN cord-014597-66vd2mdu 1238 3 , , , cord-014597-66vd2mdu 1238 4 a a DT cord-014597-66vd2mdu 1238 5 drifting drift VBG cord-014597-66vd2mdu 1238 6 CCP CCP NNP cord-014597-66vd2mdu 1238 7 reaches reach VBZ cord-014597-66vd2mdu 1238 8 the the DT cord-014597-66vd2mdu 1238 9 lower low JJR cord-014597-66vd2mdu 1238 10 or or CC cord-014597-66vd2mdu 1238 11 upper upper JJ cord-014597-66vd2mdu 1238 12 limit limit NN cord-014597-66vd2mdu 1238 13 of of IN cord-014597-66vd2mdu 1238 14 the the DT cord-014597-66vd2mdu 1238 15 accepted accept VBN cord-014597-66vd2mdu 1238 16 range range NN cord-014597-66vd2mdu 1238 17 . . . cord-014597-66vd2mdu 1239 1 The the DT cord-014597-66vd2mdu 1239 2 timepoints timepoint NNS cord-014597-66vd2mdu 1239 3 at at IN cord-014597-66vd2mdu 1239 4 which which WDT cord-014597-66vd2mdu 1239 5 those those DT cord-014597-66vd2mdu 1239 6 transitions transition NNS cord-014597-66vd2mdu 1239 7 take take VBP cord-014597-66vd2mdu 1239 8 place place NN cord-014597-66vd2mdu 1239 9 are be VBP cord-014597-66vd2mdu 1239 10 here here RB cord-014597-66vd2mdu 1239 11 called call VBN cord-014597-66vd2mdu 1239 12 changepoints changepoint NNS cord-014597-66vd2mdu 1239 13 . . . cord-014597-66vd2mdu 1240 1 Those those DT cord-014597-66vd2mdu 1240 2 are be VBP cord-014597-66vd2mdu 1240 3 aspects aspect NNS cord-014597-66vd2mdu 1240 4 of of IN cord-014597-66vd2mdu 1240 5 the the DT cord-014597-66vd2mdu 1240 6 process process NN cord-014597-66vd2mdu 1240 7 and and CC cord-014597-66vd2mdu 1240 8 , , , cord-014597-66vd2mdu 1240 9 as as IN cord-014597-66vd2mdu 1240 10 such such JJ cord-014597-66vd2mdu 1240 11 , , , cord-014597-66vd2mdu 1240 12 should should MD cord-014597-66vd2mdu 1240 13 be be VB cord-014597-66vd2mdu 1240 14 controlled control VBN cord-014597-66vd2mdu 1240 15 . . . cord-014597-66vd2mdu 1241 1 In in IN cord-014597-66vd2mdu 1241 2 the the DT cord-014597-66vd2mdu 1241 3 multiple multiple JJ cord-014597-66vd2mdu 1241 4 changepoints changepoint NNS cord-014597-66vd2mdu 1241 5 cases case NNS cord-014597-66vd2mdu 1241 6 , , , cord-014597-66vd2mdu 1241 7 the the DT cord-014597-66vd2mdu 1241 8 approach approach NN cord-014597-66vd2mdu 1241 9 allows allow VBZ cord-014597-66vd2mdu 1241 10 the the DT cord-014597-66vd2mdu 1241 11 early early JJ cord-014597-66vd2mdu 1241 12 termination termination NN cord-014597-66vd2mdu 1241 13 of of IN cord-014597-66vd2mdu 1241 14 runs run NNS cord-014597-66vd2mdu 1241 15 showing show VBG cord-014597-66vd2mdu 1241 16 very very RB cord-014597-66vd2mdu 1241 17 early early RB cord-014597-66vd2mdu 1241 18 or or CC cord-014597-66vd2mdu 1241 19 very very RB cord-014597-66vd2mdu 1241 20 late late JJ cord-014597-66vd2mdu 1241 21 first first JJ cord-014597-66vd2mdu 1241 22 changepoint changepoint NN cord-014597-66vd2mdu 1241 23 . . . cord-014597-66vd2mdu 1242 1 The the DT cord-014597-66vd2mdu 1242 2 identification identification NN cord-014597-66vd2mdu 1242 3 of of IN cord-014597-66vd2mdu 1242 4 the the DT cord-014597-66vd2mdu 1242 5 changepoints changepoint NNS cord-014597-66vd2mdu 1242 6 position position NN cord-014597-66vd2mdu 1242 7 is be VBZ cord-014597-66vd2mdu 1242 8 based base VBN cord-014597-66vd2mdu 1242 9 on on IN cord-014597-66vd2mdu 1242 10 simple simple JJ cord-014597-66vd2mdu 1242 11 rules rule NNS cord-014597-66vd2mdu 1242 12 rather rather RB cord-014597-66vd2mdu 1242 13 than than IN cord-014597-66vd2mdu 1242 14 complex complex JJ cord-014597-66vd2mdu 1242 15 statistical statistical JJ cord-014597-66vd2mdu 1242 16 modeling modeling NN cord-014597-66vd2mdu 1242 17 to to TO cord-014597-66vd2mdu 1242 18 keep keep VB cord-014597-66vd2mdu 1242 19 the the DT cord-014597-66vd2mdu 1242 20 identification identification NN cord-014597-66vd2mdu 1242 21 methodology methodology NN cord-014597-66vd2mdu 1242 22 simple simple JJ cord-014597-66vd2mdu 1242 23 . . . cord-014597-66vd2mdu 1243 1 Once once IN cord-014597-66vd2mdu 1243 2 the the DT cord-014597-66vd2mdu 1243 3 changepoint changepoint NN cord-014597-66vd2mdu 1243 4 are be VBP cord-014597-66vd2mdu 1243 5 identified identify VBN cord-014597-66vd2mdu 1243 6 , , , cord-014597-66vd2mdu 1243 7 a a DT cord-014597-66vd2mdu 1243 8 multivariate multivariate JJ cord-014597-66vd2mdu 1243 9 Bayesian bayesian JJ cord-014597-66vd2mdu 1243 10 model model NN cord-014597-66vd2mdu 1243 11 is be VBZ cord-014597-66vd2mdu 1243 12 adjusted adjust VBN cord-014597-66vd2mdu 1243 13 on on IN cord-014597-66vd2mdu 1243 14 the the DT cord-014597-66vd2mdu 1243 15 appropriately appropriately RB cord-014597-66vd2mdu 1243 16 transformed transform VBN cord-014597-66vd2mdu 1243 17 data datum NNS cord-014597-66vd2mdu 1243 18 . . . cord-014597-66vd2mdu 1244 1 Prediction prediction NN cord-014597-66vd2mdu 1244 2 regions region NNS cord-014597-66vd2mdu 1244 3 are be VBP cord-014597-66vd2mdu 1244 4 obtained obtain VBN cord-014597-66vd2mdu 1244 5 and and CC cord-014597-66vd2mdu 1244 6 used use VBN cord-014597-66vd2mdu 1244 7 as as IN cord-014597-66vd2mdu 1244 8 control control NN cord-014597-66vd2mdu 1244 9 limits limit NNS cord-014597-66vd2mdu 1244 10 [ [ -LRB- cord-014597-66vd2mdu 1244 11 1 1 CD cord-014597-66vd2mdu 1244 12 ] ] -RRB- cord-014597-66vd2mdu 1244 13 . . . cord-014597-66vd2mdu 1245 1 Results result NNS cord-014597-66vd2mdu 1245 2 obtained obtain VBN cord-014597-66vd2mdu 1245 3 for for IN cord-014597-66vd2mdu 1245 4 a a DT cord-014597-66vd2mdu 1245 5 2-changepoint 2-changepoint CD cord-014597-66vd2mdu 1245 6 case case NN cord-014597-66vd2mdu 1245 7 are be VBP cord-014597-66vd2mdu 1245 8 shown show VBN cord-014597-66vd2mdu 1245 9 on on IN cord-014597-66vd2mdu 1245 10 Fig Fig NNP cord-014597-66vd2mdu 1245 11 . . . cord-014597-66vd2mdu 1246 1 1 1 LS cord-014597-66vd2mdu 1246 2 . . . cord-014597-66vd2mdu 1247 1 Points point NNS cord-014597-66vd2mdu 1247 2 on on IN cord-014597-66vd2mdu 1247 3 the the DT cord-014597-66vd2mdu 1247 4 right right JJ cord-014597-66vd2mdu 1247 5 - - HYPH cord-014597-66vd2mdu 1247 6 hand hand NN cord-014597-66vd2mdu 1247 7 graph graph NN cord-014597-66vd2mdu 1247 8 represent represent VBP cord-014597-66vd2mdu 1247 9 new new JJ cord-014597-66vd2mdu 1247 10 batches batch NNS cord-014597-66vd2mdu 1247 11 . . . cord-014597-66vd2mdu 1248 1 The the DT cord-014597-66vd2mdu 1248 2 red red JJ cord-014597-66vd2mdu 1248 3 triangle triangle NN cord-014597-66vd2mdu 1248 4 represents represent VBZ cord-014597-66vd2mdu 1248 5 a a DT cord-014597-66vd2mdu 1248 6 failed fail VBN cord-014597-66vd2mdu 1248 7 batch batch NN cord-014597-66vd2mdu 1248 8 . . . cord-014597-66vd2mdu 1249 1 It -PRON- PRP cord-014597-66vd2mdu 1249 2 appears appear VBZ cord-014597-66vd2mdu 1249 3 that that IN cord-014597-66vd2mdu 1249 4 the the DT cord-014597-66vd2mdu 1249 5 control control NN cord-014597-66vd2mdu 1249 6 strategy strategy NN cord-014597-66vd2mdu 1249 7 fails fail VBZ cord-014597-66vd2mdu 1249 8 to to TO cord-014597-66vd2mdu 1249 9 identify identify VB cord-014597-66vd2mdu 1249 10 the the DT cord-014597-66vd2mdu 1249 11 failed fail VBN cord-014597-66vd2mdu 1249 12 batch batch NN cord-014597-66vd2mdu 1249 13 . . . cord-014597-66vd2mdu 1250 1 Two two CD cord-014597-66vd2mdu 1250 2 reasons reason NNS cord-014597-66vd2mdu 1250 3 can can MD cord-014597-66vd2mdu 1250 4 be be VB cord-014597-66vd2mdu 1250 5 considered consider VBN cord-014597-66vd2mdu 1250 6 : : : cord-014597-66vd2mdu 1250 7 -The -the WDT cord-014597-66vd2mdu 1250 8 limits limit NNS cord-014597-66vd2mdu 1250 9 of of IN cord-014597-66vd2mdu 1250 10 the the DT cord-014597-66vd2mdu 1250 11 prediction prediction NN cord-014597-66vd2mdu 1250 12 region region NN cord-014597-66vd2mdu 1250 13 have have VBP cord-014597-66vd2mdu 1250 14 been be VBN cord-014597-66vd2mdu 1250 15 established establish VBN cord-014597-66vd2mdu 1250 16 based base VBN cord-014597-66vd2mdu 1250 17 on on IN cord-014597-66vd2mdu 1250 18 9 9 CD cord-014597-66vd2mdu 1250 19 points point NNS cord-014597-66vd2mdu 1250 20 , , , cord-014597-66vd2mdu 1250 21 such such PDT cord-014597-66vd2mdu 1250 22 a a DT cord-014597-66vd2mdu 1250 23 small small JJ cord-014597-66vd2mdu 1250 24 sample sample NN cord-014597-66vd2mdu 1250 25 size size NN cord-014597-66vd2mdu 1250 26 is be VBZ cord-014597-66vd2mdu 1250 27 likely likely JJ cord-014597-66vd2mdu 1250 28 to to TO cord-014597-66vd2mdu 1250 29 be be VB cord-014597-66vd2mdu 1250 30 insufficient insufficient JJ cord-014597-66vd2mdu 1250 31 for for IN cord-014597-66vd2mdu 1250 32 the the DT cord-014597-66vd2mdu 1250 33 definition definition NN cord-014597-66vd2mdu 1250 34 of of IN cord-014597-66vd2mdu 1250 35 such such PDT cord-014597-66vd2mdu 1250 36 a a DT cord-014597-66vd2mdu 1250 37 control control NN cord-014597-66vd2mdu 1250 38 chart chart NN cord-014597-66vd2mdu 1250 39 . . . cord-014597-66vd2mdu 1251 1 -The -The : cord-014597-66vd2mdu 1251 2 tested test VBN cord-014597-66vd2mdu 1251 3 batches batch NNS cord-014597-66vd2mdu 1251 4 were be VBD cord-014597-66vd2mdu 1251 5 produced produce VBN cord-014597-66vd2mdu 1251 6 out out IN cord-014597-66vd2mdu 1251 7 of of IN cord-014597-66vd2mdu 1251 8 set set NN cord-014597-66vd2mdu 1251 9 point point NN cord-014597-66vd2mdu 1251 10 . . . cord-014597-66vd2mdu 1252 1 A a DT cord-014597-66vd2mdu 1252 2 control control NN cord-014597-66vd2mdu 1252 3 chart chart NN cord-014597-66vd2mdu 1252 4 should should MD cord-014597-66vd2mdu 1252 5 be be VB cord-014597-66vd2mdu 1252 6 used use VBN cord-014597-66vd2mdu 1252 7 on on IN cord-014597-66vd2mdu 1252 8 a a DT cord-014597-66vd2mdu 1252 9 stable stable JJ cord-014597-66vd2mdu 1252 10 process process NN cord-014597-66vd2mdu 1252 11 , , , cord-014597-66vd2mdu 1252 12 ran run VBD cord-014597-66vd2mdu 1252 13 in in IN cord-014597-66vd2mdu 1252 14 the the DT cord-014597-66vd2mdu 1252 15 same same JJ cord-014597-66vd2mdu 1252 16 conditions condition NNS cord-014597-66vd2mdu 1252 17 , , , cord-014597-66vd2mdu 1252 18 in in IN cord-014597-66vd2mdu 1252 19 order order NN cord-014597-66vd2mdu 1252 20 to to TO cord-014597-66vd2mdu 1252 21 be be VB cord-014597-66vd2mdu 1252 22 really really RB cord-014597-66vd2mdu 1252 23 relevant relevant JJ cord-014597-66vd2mdu 1252 24 . . . cord-014597-66vd2mdu 1253 1 This this DT cord-014597-66vd2mdu 1253 2 work work NN cord-014597-66vd2mdu 1253 3 was be VBD cord-014597-66vd2mdu 1253 4 based base VBN cord-014597-66vd2mdu 1253 5 on on IN cord-014597-66vd2mdu 1253 6 available available JJ cord-014597-66vd2mdu 1253 7 historical historical JJ cord-014597-66vd2mdu 1253 8 data datum NNS cord-014597-66vd2mdu 1253 9 , , , cord-014597-66vd2mdu 1253 10 which which WDT cord-014597-66vd2mdu 1253 11 is be VBZ cord-014597-66vd2mdu 1253 12 never never RB cord-014597-66vd2mdu 1253 13 an an DT cord-014597-66vd2mdu 1253 14 ideal ideal JJ cord-014597-66vd2mdu 1253 15 situation situation NN cord-014597-66vd2mdu 1253 16 . . . cord-014597-66vd2mdu 1254 1 The the DT cord-014597-66vd2mdu 1254 2 suggested suggested JJ cord-014597-66vd2mdu 1254 3 strategy strategy NN cord-014597-66vd2mdu 1254 4 offers offer VBZ cord-014597-66vd2mdu 1254 5 a a DT cord-014597-66vd2mdu 1254 6 simple simple JJ cord-014597-66vd2mdu 1254 7 approach approach NN cord-014597-66vd2mdu 1254 8 to to IN cord-014597-66vd2mdu 1254 9 the the DT cord-014597-66vd2mdu 1254 10 monitoring monitoring NN cord-014597-66vd2mdu 1254 11 of of IN cord-014597-66vd2mdu 1254 12 between between IN cord-014597-66vd2mdu 1254 13 - - HYPH cord-014597-66vd2mdu 1254 14 batch batch NN cord-014597-66vd2mdu 1254 15 behavior behavior NN cord-014597-66vd2mdu 1254 16 for for IN cord-014597-66vd2mdu 1254 17 cell cell NN cord-014597-66vd2mdu 1254 18 - - HYPH cord-014597-66vd2mdu 1254 19 culture culture NN cord-014597-66vd2mdu 1254 20 . . . cord-014597-66vd2mdu 1255 1 Once once IN cord-014597-66vd2mdu 1255 2 the the DT cord-014597-66vd2mdu 1255 3 limits limit NNS cord-014597-66vd2mdu 1255 4 have have VBP cord-014597-66vd2mdu 1255 5 been be VBN cord-014597-66vd2mdu 1255 6 defined define VBN cord-014597-66vd2mdu 1255 7 , , , cord-014597-66vd2mdu 1255 8 the the DT cord-014597-66vd2mdu 1255 9 approach approach NN cord-014597-66vd2mdu 1255 10 is be VBZ cord-014597-66vd2mdu 1255 11 quite quite RB cord-014597-66vd2mdu 1255 12 straightforward straightforward JJ cord-014597-66vd2mdu 1255 13 and and CC cord-014597-66vd2mdu 1255 14 usable usable JJ cord-014597-66vd2mdu 1255 15 by by IN cord-014597-66vd2mdu 1255 16 nonstatistician nonstatistician NNP cord-014597-66vd2mdu 1255 17 . . . cord-014597-66vd2mdu 1256 1 However however RB cord-014597-66vd2mdu 1256 2 , , , cord-014597-66vd2mdu 1256 3 such such JJ cord-014597-66vd2mdu 1256 4 strategy strategy NN cord-014597-66vd2mdu 1256 5 , , , cord-014597-66vd2mdu 1256 6 as as IN cord-014597-66vd2mdu 1256 7 any any DT cord-014597-66vd2mdu 1256 8 other other JJ cord-014597-66vd2mdu 1256 9 of of IN cord-014597-66vd2mdu 1256 10 this this DT cord-014597-66vd2mdu 1256 11 type type NN cord-014597-66vd2mdu 1256 12 , , , cord-014597-66vd2mdu 1256 13 must must MD cord-014597-66vd2mdu 1256 14 be be VB cord-014597-66vd2mdu 1256 15 based base VBN cord-014597-66vd2mdu 1256 16 on on IN cord-014597-66vd2mdu 1256 17 a a DT cord-014597-66vd2mdu 1256 18 sufficient sufficient JJ cord-014597-66vd2mdu 1256 19 number number NN cord-014597-66vd2mdu 1256 20 of of IN cord-014597-66vd2mdu 1256 21 batches batch NNS cord-014597-66vd2mdu 1256 22 for for IN cord-014597-66vd2mdu 1256 23 the the DT cord-014597-66vd2mdu 1256 24 definition definition NN cord-014597-66vd2mdu 1256 25 of of IN cord-014597-66vd2mdu 1256 26 the the DT cord-014597-66vd2mdu 1256 27 control control NN cord-014597-66vd2mdu 1256 28 limits limit NNS cord-014597-66vd2mdu 1256 29 in in IN cord-014597-66vd2mdu 1256 30 order order NN cord-014597-66vd2mdu 1256 31 to to TO cord-014597-66vd2mdu 1256 32 have have VB cord-014597-66vd2mdu 1256 33 a a DT cord-014597-66vd2mdu 1256 34 good good JJ cord-014597-66vd2mdu 1256 35 estimation estimation NN cord-014597-66vd2mdu 1256 36 of of IN cord-014597-66vd2mdu 1256 37 the the DT cord-014597-66vd2mdu 1256 38 batch batch NN cord-014597-66vd2mdu 1256 39 - - HYPH cord-014597-66vd2mdu 1256 40 to to TO cord-014597-66vd2mdu 1256 41 batch batch VB cord-014597-66vd2mdu 1256 42 variability variability NN cord-014597-66vd2mdu 1256 43 . . . cord-014597-66vd2mdu 1257 1 Fig Fig NNP cord-014597-66vd2mdu 1257 2 . . . cord-014597-66vd2mdu 1257 3 1 1 CD cord-014597-66vd2mdu 1257 4 ( ( -LRB- cord-014597-66vd2mdu 1257 5 abstract abstract JJ cord-014597-66vd2mdu 1257 6 P-190 p-190 NN cord-014597-66vd2mdu 1257 7 ) ) -RRB- cord-014597-66vd2mdu 1257 8 . . . cord-014597-66vd2mdu 1258 1 Intelligent intelligent JJ cord-014597-66vd2mdu 1258 2 software software NN cord-014597-66vd2mdu 1258 3 applications application NNS cord-014597-66vd2mdu 1258 4 support support VBP cord-014597-66vd2mdu 1258 5 digital digital JJ cord-014597-66vd2mdu 1258 6 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 1258 7 process process NN cord-014597-66vd2mdu 1258 8 development development NN cord-014597-66vd2mdu 1258 9 and and CC cord-014597-66vd2mdu 1258 10 control control NN cord-014597-66vd2mdu 1258 11 . . . cord-014597-66vd2mdu 1259 1 • • NNP cord-014597-66vd2mdu 1260 1 Databases database NNS cord-014597-66vd2mdu 1260 2 using use VBG cord-014597-66vd2mdu 1260 3 data datum NNS cord-014597-66vd2mdu 1260 4 collected collect VBN cord-014597-66vd2mdu 1260 5 online online RB cord-014597-66vd2mdu 1260 6 , , , cord-014597-66vd2mdu 1260 7 at at IN cord-014597-66vd2mdu 1260 8 - - HYPH cord-014597-66vd2mdu 1260 9 line line NN cord-014597-66vd2mdu 1260 10 , , , cord-014597-66vd2mdu 1260 11 and and CC cord-014597-66vd2mdu 1260 12 offline offline JJ cord-014597-66vd2mdu 1260 13 from from IN cord-014597-66vd2mdu 1260 14 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 1260 15 operating operate VBG cord-014597-66vd2mdu 1260 16 worldwide worldwide RB cord-014597-66vd2mdu 1260 17 . . . cord-014597-66vd2mdu 1261 1 • • NNP cord-014597-66vd2mdu 1261 2 Process Process NNP cord-014597-66vd2mdu 1261 3 data datum NNS cord-014597-66vd2mdu 1261 4 are be VBP cord-014597-66vd2mdu 1261 5 used use VBN cord-014597-66vd2mdu 1261 6 to to TO cord-014597-66vd2mdu 1261 7 generate generate VB cord-014597-66vd2mdu 1261 8 metabolic metabolic JJ cord-014597-66vd2mdu 1261 9 network network NN cord-014597-66vd2mdu 1261 10 models model NNS cord-014597-66vd2mdu 1261 11 that that WDT cord-014597-66vd2mdu 1261 12 represent represent VBP cord-014597-66vd2mdu 1261 13 a a DT cord-014597-66vd2mdu 1261 14 specific specific JJ cord-014597-66vd2mdu 1261 15 host host NN cord-014597-66vd2mdu 1261 16 cell cell NN cord-014597-66vd2mdu 1261 17 line line NN cord-014597-66vd2mdu 1261 18 in in IN cord-014597-66vd2mdu 1261 19 a a DT cord-014597-66vd2mdu 1261 20 bioprocess bioprocess NN cord-014597-66vd2mdu 1261 21 . . . cord-014597-66vd2mdu 1262 1 • • NNP cord-014597-66vd2mdu 1263 1 Modelbased modelbased JJ cord-014597-66vd2mdu 1263 2 computational computational JJ cord-014597-66vd2mdu 1263 3 simulations simulation NNS cord-014597-66vd2mdu 1263 4 improve improve VBP cord-014597-66vd2mdu 1263 5 process process NN cord-014597-66vd2mdu 1263 6 understanding understanding NN cord-014597-66vd2mdu 1263 7 and and CC cord-014597-66vd2mdu 1263 8 reduce reduce VB cord-014597-66vd2mdu 1263 9 experimental experimental JJ cord-014597-66vd2mdu 1263 10 efforts effort NNS cord-014597-66vd2mdu 1263 11 for for IN cord-014597-66vd2mdu 1263 12 media medium NNS cord-014597-66vd2mdu 1263 13 design design NN cord-014597-66vd2mdu 1263 14 , , , cord-014597-66vd2mdu 1263 15 clone clone NN cord-014597-66vd2mdu 1263 16 selection selection NN cord-014597-66vd2mdu 1263 17 , , , cord-014597-66vd2mdu 1263 18 and and CC cord-014597-66vd2mdu 1263 19 metabolic metabolic JJ cord-014597-66vd2mdu 1263 20 engineering engineering NN cord-014597-66vd2mdu 1263 21 . . . cord-014597-66vd2mdu 1264 1 • • NNP cord-014597-66vd2mdu 1265 1 Automated automate VBN cord-014597-66vd2mdu 1265 2 data data NN cord-014597-66vd2mdu 1265 3 import import NN cord-014597-66vd2mdu 1265 4 and and CC cord-014597-66vd2mdu 1265 5 processing processing NN cord-014597-66vd2mdu 1265 6 allow allow VB cord-014597-66vd2mdu 1265 7 for for IN cord-014597-66vd2mdu 1265 8 a a DT cord-014597-66vd2mdu 1265 9 streamlined streamlined JJ cord-014597-66vd2mdu 1265 10 and and CC cord-014597-66vd2mdu 1265 11 standardized standardized JJ cord-014597-66vd2mdu 1265 12 metabolic metabolic JJ cord-014597-66vd2mdu 1265 13 process process NN cord-014597-66vd2mdu 1265 14 analysis analysis NN cord-014597-66vd2mdu 1265 15 . . . cord-014597-66vd2mdu 1266 1 • • NNP cord-014597-66vd2mdu 1267 1 Identification identification NN cord-014597-66vd2mdu 1267 2 of of IN cord-014597-66vd2mdu 1267 3 critical critical JJ cord-014597-66vd2mdu 1267 4 metabolic metabolic JJ cord-014597-66vd2mdu 1267 5 parameters parameter NNS cord-014597-66vd2mdu 1267 6 is be VBZ cord-014597-66vd2mdu 1267 7 used use VBN cord-014597-66vd2mdu 1267 8 for for IN cord-014597-66vd2mdu 1267 9 proactive proactive JJ cord-014597-66vd2mdu 1267 10 steering steering NN cord-014597-66vd2mdu 1267 11 and and CC cord-014597-66vd2mdu 1267 12 control control NN cord-014597-66vd2mdu 1267 13 of of IN cord-014597-66vd2mdu 1267 14 production production NN cord-014597-66vd2mdu 1267 15 processes process NNS cord-014597-66vd2mdu 1268 1 Background Background NNP cord-014597-66vd2mdu 1268 2 Rabies Rabies NNP cord-014597-66vd2mdu 1268 3 is be VBZ cord-014597-66vd2mdu 1268 4 a a DT cord-014597-66vd2mdu 1268 5 zoonotic zoonotic JJ cord-014597-66vd2mdu 1268 6 viral viral JJ cord-014597-66vd2mdu 1268 7 disease disease NN cord-014597-66vd2mdu 1268 8 with with IN cord-014597-66vd2mdu 1268 9 a a DT cord-014597-66vd2mdu 1268 10 mortality mortality NN cord-014597-66vd2mdu 1268 11 close close JJ cord-014597-66vd2mdu 1268 12 to to IN cord-014597-66vd2mdu 1268 13 100 100 CD cord-014597-66vd2mdu 1268 14 % % NN cord-014597-66vd2mdu 1268 15 [ [ -LRB- cord-014597-66vd2mdu 1268 16 1 1 CD cord-014597-66vd2mdu 1268 17 ] ] -RRB- cord-014597-66vd2mdu 1268 18 . . . cord-014597-66vd2mdu 1269 1 As as IN cord-014597-66vd2mdu 1269 2 there there EX cord-014597-66vd2mdu 1269 3 is be VBZ cord-014597-66vd2mdu 1269 4 not not RB cord-014597-66vd2mdu 1269 5 an an DT cord-014597-66vd2mdu 1269 6 efficacious efficacious JJ cord-014597-66vd2mdu 1269 7 treatment treatment NN cord-014597-66vd2mdu 1269 8 available available JJ cord-014597-66vd2mdu 1269 9 , , , cord-014597-66vd2mdu 1269 10 post post JJ cord-014597-66vd2mdu 1269 11 - - JJ cord-014597-66vd2mdu 1269 12 exposure exposure JJ cord-014597-66vd2mdu 1269 13 vaccination vaccination NN cord-014597-66vd2mdu 1269 14 is be VBZ cord-014597-66vd2mdu 1269 15 recommended recommend VBN cord-014597-66vd2mdu 1269 16 for for IN cord-014597-66vd2mdu 1269 17 individuals individual NNS cord-014597-66vd2mdu 1269 18 in in IN cord-014597-66vd2mdu 1269 19 contact contact NN cord-014597-66vd2mdu 1269 20 with with IN cord-014597-66vd2mdu 1269 21 the the DT cord-014597-66vd2mdu 1269 22 virus virus NN cord-014597-66vd2mdu 1269 23 . . . cord-014597-66vd2mdu 1270 1 On on IN cord-014597-66vd2mdu 1270 2 the the DT cord-014597-66vd2mdu 1270 3 other other JJ cord-014597-66vd2mdu 1270 4 hand hand NN cord-014597-66vd2mdu 1270 5 , , , cord-014597-66vd2mdu 1270 6 the the DT cord-014597-66vd2mdu 1270 7 most most RBS cord-014597-66vd2mdu 1270 8 common common JJ cord-014597-66vd2mdu 1270 9 source source NN cord-014597-66vd2mdu 1270 10 of of IN cord-014597-66vd2mdu 1270 11 virus virus NN cord-014597-66vd2mdu 1270 12 transmission transmission NN cord-014597-66vd2mdu 1270 13 is be VBZ cord-014597-66vd2mdu 1270 14 saliva saliva NN cord-014597-66vd2mdu 1270 15 of of IN cord-014597-66vd2mdu 1270 16 infected infected JJ cord-014597-66vd2mdu 1270 17 animals animal NNS cord-014597-66vd2mdu 1270 18 , , , cord-014597-66vd2mdu 1270 19 mostly mostly RB cord-014597-66vd2mdu 1270 20 dogs dog NNS cord-014597-66vd2mdu 1270 21 , , , cord-014597-66vd2mdu 1270 22 whereby whereby WRB cord-014597-66vd2mdu 1270 23 mass mass JJ cord-014597-66vd2mdu 1270 24 vaccination vaccination NN cord-014597-66vd2mdu 1270 25 of of IN cord-014597-66vd2mdu 1270 26 pets pet NNS cord-014597-66vd2mdu 1270 27 is be VBZ cord-014597-66vd2mdu 1270 28 the the DT cord-014597-66vd2mdu 1270 29 most most RBS cord-014597-66vd2mdu 1270 30 cost cost NN cord-014597-66vd2mdu 1270 31 - - HYPH cord-014597-66vd2mdu 1270 32 effective effective JJ cord-014597-66vd2mdu 1270 33 way way NN cord-014597-66vd2mdu 1270 34 to to TO cord-014597-66vd2mdu 1270 35 reduce reduce VB cord-014597-66vd2mdu 1270 36 human human JJ cord-014597-66vd2mdu 1270 37 infections infection NNS cord-014597-66vd2mdu 1270 38 . . . cord-014597-66vd2mdu 1271 1 In in IN cord-014597-66vd2mdu 1271 2 this this DT cord-014597-66vd2mdu 1271 3 context context NN cord-014597-66vd2mdu 1271 4 , , , cord-014597-66vd2mdu 1271 5 availability availability NN cord-014597-66vd2mdu 1271 6 of of IN cord-014597-66vd2mdu 1271 7 both both DT cord-014597-66vd2mdu 1271 8 human human JJ cord-014597-66vd2mdu 1271 9 and and CC cord-014597-66vd2mdu 1271 10 veterinary veterinary JJ cord-014597-66vd2mdu 1271 11 vaccines vaccine NNS cord-014597-66vd2mdu 1271 12 is be VBZ cord-014597-66vd2mdu 1271 13 critical critical JJ cord-014597-66vd2mdu 1271 14 [ [ -LRB- cord-014597-66vd2mdu 1271 15 2 2 CD cord-014597-66vd2mdu 1271 16 , , , cord-014597-66vd2mdu 1271 17 3 3 CD cord-014597-66vd2mdu 1271 18 ] ] -RRB- cord-014597-66vd2mdu 1271 19 . . . cord-014597-66vd2mdu 1272 1 Our -PRON- PRP$ cord-014597-66vd2mdu 1272 2 group group NN cord-014597-66vd2mdu 1272 3 had have VBD cord-014597-66vd2mdu 1272 4 previously previously RB cord-014597-66vd2mdu 1272 5 developed develop VBN cord-014597-66vd2mdu 1272 6 an an DT cord-014597-66vd2mdu 1272 7 effective effective JJ cord-014597-66vd2mdu 1272 8 VLP VLP NNP cord-014597-66vd2mdu 1272 9 - - HYPH cord-014597-66vd2mdu 1272 10 based base VBN cord-014597-66vd2mdu 1272 11 rabies rabie NNS cord-014597-66vd2mdu 1272 12 vaccine vaccine NN cord-014597-66vd2mdu 1272 13 candidate candidate NN cord-014597-66vd2mdu 1272 14 produced produce VBN cord-014597-66vd2mdu 1272 15 in in IN cord-014597-66vd2mdu 1272 16 high high JJ cord-014597-66vd2mdu 1272 17 density density NN cord-014597-66vd2mdu 1272 18 HEK293 HEK293 NNP cord-014597-66vd2mdu 1272 19 cell cell NN cord-014597-66vd2mdu 1272 20 cultures culture NNS cord-014597-66vd2mdu 1272 21 with with IN cord-014597-66vd2mdu 1272 22 serum serum NN cord-014597-66vd2mdu 1272 23 free free JJ cord-014597-66vd2mdu 1272 24 medium medium NN cord-014597-66vd2mdu 1272 25 ( ( -LRB- cord-014597-66vd2mdu 1272 26 SFM SFM NNP cord-014597-66vd2mdu 1272 27 ) ) -RRB- cord-014597-66vd2mdu 1272 28 [ [ -LRB- cord-014597-66vd2mdu 1272 29 4 4 CD cord-014597-66vd2mdu 1272 30 , , , cord-014597-66vd2mdu 1272 31 5 5 CD cord-014597-66vd2mdu 1272 32 ] ] -RRB- cord-014597-66vd2mdu 1272 33 . . . cord-014597-66vd2mdu 1273 1 One one CD cord-014597-66vd2mdu 1273 2 of of IN cord-014597-66vd2mdu 1273 3 the the DT cord-014597-66vd2mdu 1273 4 aims aim NNS cord-014597-66vd2mdu 1273 5 in in IN cord-014597-66vd2mdu 1273 6 vaccine vaccine NN cord-014597-66vd2mdu 1273 7 production production NN cord-014597-66vd2mdu 1273 8 process process NN cord-014597-66vd2mdu 1273 9 is be VBZ cord-014597-66vd2mdu 1273 10 the the DT cord-014597-66vd2mdu 1273 11 achievement achievement NN cord-014597-66vd2mdu 1273 12 of of IN cord-014597-66vd2mdu 1273 13 a a DT cord-014597-66vd2mdu 1273 14 good good JJ cord-014597-66vd2mdu 1273 15 productivity productivity NN cord-014597-66vd2mdu 1273 16 with with IN cord-014597-66vd2mdu 1273 17 a a DT cord-014597-66vd2mdu 1273 18 low low JJ cord-014597-66vd2mdu 1273 19 cost cost NN cord-014597-66vd2mdu 1273 20 per per IN cord-014597-66vd2mdu 1273 21 dose dose NN cord-014597-66vd2mdu 1273 22 , , , cord-014597-66vd2mdu 1273 23 mainly mainly RB cord-014597-66vd2mdu 1273 24 in in IN cord-014597-66vd2mdu 1273 25 the the DT cord-014597-66vd2mdu 1273 26 case case NN cord-014597-66vd2mdu 1273 27 of of IN cord-014597-66vd2mdu 1273 28 vaccines vaccine NNS cord-014597-66vd2mdu 1273 29 for for IN cord-014597-66vd2mdu 1273 30 animal animal NN cord-014597-66vd2mdu 1273 31 use use NN cord-014597-66vd2mdu 1273 32 in in IN cord-014597-66vd2mdu 1273 33 which which WDT cord-014597-66vd2mdu 1273 34 case case NN cord-014597-66vd2mdu 1273 35 the the DT cord-014597-66vd2mdu 1273 36 SFM SFM NNP cord-014597-66vd2mdu 1273 37 is be VBZ cord-014597-66vd2mdu 1273 38 one one CD cord-014597-66vd2mdu 1273 39 of of IN cord-014597-66vd2mdu 1273 40 the the DT cord-014597-66vd2mdu 1273 41 principal principal JJ cord-014597-66vd2mdu 1273 42 expenses expense NNS cord-014597-66vd2mdu 1273 43 . . . cord-014597-66vd2mdu 1274 1 In in IN cord-014597-66vd2mdu 1274 2 this this DT cord-014597-66vd2mdu 1274 3 work work NN cord-014597-66vd2mdu 1274 4 , , , cord-014597-66vd2mdu 1274 5 we -PRON- PRP cord-014597-66vd2mdu 1274 6 show show VBP cord-014597-66vd2mdu 1274 7 the the DT cord-014597-66vd2mdu 1274 8 adaptation adaptation NN cord-014597-66vd2mdu 1274 9 of of IN cord-014597-66vd2mdu 1274 10 the the DT cord-014597-66vd2mdu 1274 11 producer producer NN cord-014597-66vd2mdu 1274 12 clone clone NN cord-014597-66vd2mdu 1274 13 to to IN cord-014597-66vd2mdu 1274 14 a a DT cord-014597-66vd2mdu 1274 15 non non JJ cord-014597-66vd2mdu 1274 16 - - JJ cord-014597-66vd2mdu 1274 17 expensive expensive JJ cord-014597-66vd2mdu 1274 18 in in IN cord-014597-66vd2mdu 1274 19 - - HYPH cord-014597-66vd2mdu 1274 20 house house NN cord-014597-66vd2mdu 1274 21 developed develop VBN cord-014597-66vd2mdu 1274 22 culture culture NN cord-014597-66vd2mdu 1274 23 medium medium NN cord-014597-66vd2mdu 1274 24 , , , cord-014597-66vd2mdu 1274 25 in in IN cord-014597-66vd2mdu 1274 26 order order NN cord-014597-66vd2mdu 1274 27 to to TO cord-014597-66vd2mdu 1274 28 reduce reduce VB cord-014597-66vd2mdu 1274 29 the the DT cord-014597-66vd2mdu 1274 30 global global JJ cord-014597-66vd2mdu 1274 31 cost cost NN cord-014597-66vd2mdu 1274 32 of of IN cord-014597-66vd2mdu 1274 33 the the DT cord-014597-66vd2mdu 1274 34 process process NN cord-014597-66vd2mdu 1274 35 and and CC cord-014597-66vd2mdu 1274 36 therefore therefore RB cord-014597-66vd2mdu 1274 37 the the DT cord-014597-66vd2mdu 1274 38 price price NN cord-014597-66vd2mdu 1274 39 per per IN cord-014597-66vd2mdu 1274 40 dose dose NN cord-014597-66vd2mdu 1274 41 . . . cord-014597-66vd2mdu 1275 1 Experimental experimental JJ cord-014597-66vd2mdu 1275 2 approach approach NN cord-014597-66vd2mdu 1276 1 First first RB cord-014597-66vd2mdu 1276 2 , , , cord-014597-66vd2mdu 1276 3 we -PRON- PRP cord-014597-66vd2mdu 1276 4 compared compare VBD cord-014597-66vd2mdu 1276 5 a a DT cord-014597-66vd2mdu 1276 6 direct direct JJ cord-014597-66vd2mdu 1276 7 and and CC cord-014597-66vd2mdu 1276 8 a a DT cord-014597-66vd2mdu 1276 9 sequential sequential JJ cord-014597-66vd2mdu 1276 10 adaptation adaptation NN cord-014597-66vd2mdu 1276 11 protocol protocol NN cord-014597-66vd2mdu 1276 12 of of IN cord-014597-66vd2mdu 1276 13 our -PRON- PRP$ cord-014597-66vd2mdu 1276 14 HEK293 HEK293 NNP cord-014597-66vd2mdu 1276 15 RV RV NNP cord-014597-66vd2mdu 1276 16 - - HYPH cord-014597-66vd2mdu 1276 17 VLPs vlps NN cord-014597-66vd2mdu 1276 18 producer producer NN cord-014597-66vd2mdu 1276 19 clone clone NN cord-014597-66vd2mdu 1276 20 , , , cord-014597-66vd2mdu 1276 21 from from IN cord-014597-66vd2mdu 1276 22 100 100 CD cord-014597-66vd2mdu 1276 23 % % NN cord-014597-66vd2mdu 1276 24 of of IN cord-014597-66vd2mdu 1276 25 the the DT cord-014597-66vd2mdu 1276 26 commercial commercial JJ cord-014597-66vd2mdu 1276 27 SFM SFM NNP cord-014597-66vd2mdu 1276 28 ( ( -LRB- cord-014597-66vd2mdu 1276 29 EX EX NNP cord-014597-66vd2mdu 1276 30 - - HYPH cord-014597-66vd2mdu 1276 31 CELL293 CELL293 NNP cord-014597-66vd2mdu 1276 32 , , , cord-014597-66vd2mdu 1276 33 SAFC SAFC NNP cord-014597-66vd2mdu 1276 34 ) ) -RRB- cord-014597-66vd2mdu 1276 35 to to IN cord-014597-66vd2mdu 1276 36 a a DT cord-014597-66vd2mdu 1276 37 new new JJ cord-014597-66vd2mdu 1276 38 formulation formulation NN cord-014597-66vd2mdu 1276 39 with with IN cord-014597-66vd2mdu 1276 40 only only RB cord-014597-66vd2mdu 1276 41 50 50 CD cord-014597-66vd2mdu 1276 42 % % NN cord-014597-66vd2mdu 1276 43 of of IN cord-014597-66vd2mdu 1276 44 the the DT cord-014597-66vd2mdu 1276 45 SFM SFM NNP cord-014597-66vd2mdu 1276 46 and and CC cord-014597-66vd2mdu 1276 47 a a DT cord-014597-66vd2mdu 1276 48 minimum minimum JJ cord-014597-66vd2mdu 1276 49 essential essential JJ cord-014597-66vd2mdu 1276 50 medium medium NN cord-014597-66vd2mdu 1276 51 ( ( -LRB- cord-014597-66vd2mdu 1276 52 P2 P2 NNP cord-014597-66vd2mdu 1276 53 G G NNP cord-014597-66vd2mdu 1276 54 ) ) -RRB- cord-014597-66vd2mdu 1276 55 , , , cord-014597-66vd2mdu 1276 56 developed develop VBN cord-014597-66vd2mdu 1276 57 in in IN cord-014597-66vd2mdu 1276 58 our -PRON- PRP$ cord-014597-66vd2mdu 1276 59 laboratory laboratory NN cord-014597-66vd2mdu 1276 60 specifically specifically RB cord-014597-66vd2mdu 1276 61 for for IN cord-014597-66vd2mdu 1276 62 RV rv NN cord-014597-66vd2mdu 1276 63 - - HYPH cord-014597-66vd2mdu 1276 64 VLPs vlp NNS cord-014597-66vd2mdu 1276 65 production production NN cord-014597-66vd2mdu 1276 66 . . . cord-014597-66vd2mdu 1277 1 This this DT cord-014597-66vd2mdu 1277 2 new new JJ cord-014597-66vd2mdu 1277 3 formulation formulation NN cord-014597-66vd2mdu 1277 4 was be VBD cord-014597-66vd2mdu 1277 5 called call VBN cord-014597-66vd2mdu 1277 6 RVPM RVPM NNP cord-014597-66vd2mdu 1278 1 ( ( -LRB- cord-014597-66vd2mdu 1278 2 Rabies Rabies NNP cord-014597-66vd2mdu 1278 3 Vaccine Vaccine NNP cord-014597-66vd2mdu 1278 4 Production Production NNP cord-014597-66vd2mdu 1278 5 Medium Medium NNP cord-014597-66vd2mdu 1278 6 ) ) -RRB- cord-014597-66vd2mdu 1278 7 . . . cord-014597-66vd2mdu 1279 1 The the DT cord-014597-66vd2mdu 1279 2 specific specific JJ cord-014597-66vd2mdu 1279 3 productivity productivity NN cord-014597-66vd2mdu 1279 4 of of IN cord-014597-66vd2mdu 1279 5 RV rv NN cord-014597-66vd2mdu 1279 6 - - HYPH cord-014597-66vd2mdu 1279 7 VLPs vlp NNS cord-014597-66vd2mdu 1279 8 in in IN cord-014597-66vd2mdu 1279 9 culture culture NN cord-014597-66vd2mdu 1279 10 supernatants supernatant NNS cord-014597-66vd2mdu 1279 11 was be VBD cord-014597-66vd2mdu 1279 12 measured measure VBN cord-014597-66vd2mdu 1279 13 by by IN cord-014597-66vd2mdu 1279 14 sandwich sandwich NN cord-014597-66vd2mdu 1279 15 ELISA ELISA NNP cord-014597-66vd2mdu 1279 16 , , , cord-014597-66vd2mdu 1279 17 using use VBG cord-014597-66vd2mdu 1279 18 the the DT cord-014597-66vd2mdu 1279 19 6 6 CD cord-014597-66vd2mdu 1279 20 th th NNP cord-014597-66vd2mdu 1279 21 International International NNP cord-014597-66vd2mdu 1279 22 Standard Standard NNP cord-014597-66vd2mdu 1279 23 for for IN cord-014597-66vd2mdu 1279 24 rabies rabies NN cord-014597-66vd2mdu 1279 25 vaccine vaccine NN cord-014597-66vd2mdu 1279 26 that that WDT cord-014597-66vd2mdu 1279 27 quantify quantify VBP cord-014597-66vd2mdu 1279 28 the the DT cord-014597-66vd2mdu 1279 29 glycoprotein glycoprotein NN cord-014597-66vd2mdu 1279 30 content content NN cord-014597-66vd2mdu 1279 31 ( ( -LRB- cord-014597-66vd2mdu 1279 32 NIBSC NIBSC NNP cord-014597-66vd2mdu 1279 33 , , , cord-014597-66vd2mdu 1279 34 expressed express VBN cord-014597-66vd2mdu 1279 35 in in IN cord-014597-66vd2mdu 1279 36 ELISA ELISA NNP cord-014597-66vd2mdu 1279 37 Units Units NNP cord-014597-66vd2mdu 1279 38 per per IN cord-014597-66vd2mdu 1279 39 ml ml NN cord-014597-66vd2mdu 1279 40 ) ) -RRB- cord-014597-66vd2mdu 1279 41 . . . cord-014597-66vd2mdu 1280 1 Further further RB cord-014597-66vd2mdu 1280 2 , , , cord-014597-66vd2mdu 1280 3 we -PRON- PRP cord-014597-66vd2mdu 1280 4 evaluated evaluate VBD cord-014597-66vd2mdu 1280 5 both both DT cord-014597-66vd2mdu 1280 6 media medium NNS cord-014597-66vd2mdu 1280 7 for for IN cord-014597-66vd2mdu 1280 8 the the DT cord-014597-66vd2mdu 1280 9 production production NN cord-014597-66vd2mdu 1280 10 of of IN cord-014597-66vd2mdu 1280 11 the the DT cord-014597-66vd2mdu 1280 12 rabies rabies NN cord-014597-66vd2mdu 1280 13 vaccine vaccine NN cord-014597-66vd2mdu 1280 14 , , , cord-014597-66vd2mdu 1280 15 using use VBG cord-014597-66vd2mdu 1280 16 stirred stir VBN cord-014597-66vd2mdu 1280 17 tank tank NN cord-014597-66vd2mdu 1280 18 bioreactors bioreactor NNS cord-014597-66vd2mdu 1280 19 operated operate VBN cord-014597-66vd2mdu 1280 20 in in IN cord-014597-66vd2mdu 1280 21 continuous continuous JJ cord-014597-66vd2mdu 1280 22 mode mode NN cord-014597-66vd2mdu 1280 23 ( ( -LRB- cord-014597-66vd2mdu 1280 24 BIOSTAT BIOSTAT NNP cord-014597-66vd2mdu 1280 25 QPlus QPlus NNP cord-014597-66vd2mdu 1280 26 , , , cord-014597-66vd2mdu 1280 27 Sartorius Sartorius NNP cord-014597-66vd2mdu 1280 28 ) ) -RRB- cord-014597-66vd2mdu 1280 29 . . . cord-014597-66vd2mdu 1281 1 The the DT cord-014597-66vd2mdu 1281 2 production production NN cord-014597-66vd2mdu 1281 3 of of IN cord-014597-66vd2mdu 1281 4 the the DT cord-014597-66vd2mdu 1281 5 RV RV NNP cord-014597-66vd2mdu 1281 6 - - HYPH cord-014597-66vd2mdu 1281 7 VLPs VLPs NNP cord-014597-66vd2mdu 1281 8 was be VBD cord-014597-66vd2mdu 1281 9 daily daily RB cord-014597-66vd2mdu 1281 10 evaluated evaluate VBN cord-014597-66vd2mdu 1281 11 by by IN cord-014597-66vd2mdu 1281 12 ELISA ELISA NNP cord-014597-66vd2mdu 1281 13 and and CC cord-014597-66vd2mdu 1281 14 the the DT cord-014597-66vd2mdu 1281 15 obtained obtain VBN cord-014597-66vd2mdu 1281 16 harvests harvest NNS cord-014597-66vd2mdu 1281 17 analysed analyse VBN cord-014597-66vd2mdu 1281 18 by by IN cord-014597-66vd2mdu 1281 19 the the DT cord-014597-66vd2mdu 1281 20 NIH NIH NNP cord-014597-66vd2mdu 1281 21 potency potency NN cord-014597-66vd2mdu 1281 22 test test NN cord-014597-66vd2mdu 1281 23 for for IN cord-014597-66vd2mdu 1281 24 rabies rabies NN cord-014597-66vd2mdu 1281 25 vaccine vaccine NN cord-014597-66vd2mdu 1281 26 . . . cord-014597-66vd2mdu 1282 1 After after IN cord-014597-66vd2mdu 1282 2 the the DT cord-014597-66vd2mdu 1282 3 adaptation adaptation NN cord-014597-66vd2mdu 1282 4 process process NN cord-014597-66vd2mdu 1282 5 , , , cord-014597-66vd2mdu 1282 6 suspension suspension NN cord-014597-66vd2mdu 1282 7 cultures culture NNS cord-014597-66vd2mdu 1282 8 without without IN cord-014597-66vd2mdu 1282 9 aggregates aggregate NNS cord-014597-66vd2mdu 1282 10 or or CC cord-014597-66vd2mdu 1282 11 clumps clump NNS cord-014597-66vd2mdu 1282 12 were be VBD cord-014597-66vd2mdu 1282 13 obtained obtain VBN cord-014597-66vd2mdu 1282 14 , , , cord-014597-66vd2mdu 1282 15 with with IN cord-014597-66vd2mdu 1282 16 the the DT cord-014597-66vd2mdu 1282 17 same same JJ cord-014597-66vd2mdu 1282 18 specific specific JJ cord-014597-66vd2mdu 1282 19 growth growth NN cord-014597-66vd2mdu 1282 20 rate rate NN cord-014597-66vd2mdu 1282 21 . . . cord-014597-66vd2mdu 1283 1 A a DT cord-014597-66vd2mdu 1283 2 lower low JJR cord-014597-66vd2mdu 1283 3 maximum maximum JJ cord-014597-66vd2mdu 1283 4 cell cell NN cord-014597-66vd2mdu 1283 5 density density NN cord-014597-66vd2mdu 1283 6 with with IN cord-014597-66vd2mdu 1283 7 the the DT cord-014597-66vd2mdu 1283 8 RVPM RVPM NNP cord-014597-66vd2mdu 1283 9 was be VBD cord-014597-66vd2mdu 1283 10 reached reach VBN cord-014597-66vd2mdu 1283 11 , , , cord-014597-66vd2mdu 1283 12 achieving achieve VBG cord-014597-66vd2mdu 1283 13 5x10 5x10 CD cord-014597-66vd2mdu 1283 14 6 6 CD cord-014597-66vd2mdu 1283 15 cells.ml cells.ml CD cord-014597-66vd2mdu 1283 16 -1 -1 NN cord-014597-66vd2mdu 1283 17 , , , cord-014597-66vd2mdu 1283 18 compared compare VBN cord-014597-66vd2mdu 1283 19 with with IN cord-014597-66vd2mdu 1283 20 the the DT cord-014597-66vd2mdu 1283 21 SFM SFM NNP cord-014597-66vd2mdu 1283 22 that that WDT cord-014597-66vd2mdu 1283 23 reach reach VBP cord-014597-66vd2mdu 1283 24 cell cell NN cord-014597-66vd2mdu 1283 25 densities density NNS cord-014597-66vd2mdu 1283 26 between between IN cord-014597-66vd2mdu 1283 27 8 8 CD cord-014597-66vd2mdu 1283 28 and and CC cord-014597-66vd2mdu 1283 29 9x10 9x10 CD cord-014597-66vd2mdu 1283 30 6 6 CD cord-014597-66vd2mdu 1283 31 cells.ml cells.ml CD cord-014597-66vd2mdu 1283 32 -1 -1 CD cord-014597-66vd2mdu 1283 33 in in IN cord-014597-66vd2mdu 1283 34 batch batch NN cord-014597-66vd2mdu 1283 35 mode mode NN cord-014597-66vd2mdu 1283 36 . . . cord-014597-66vd2mdu 1284 1 The the DT cord-014597-66vd2mdu 1284 2 specific specific JJ cord-014597-66vd2mdu 1284 3 RV rv NN cord-014597-66vd2mdu 1284 4 - - HYPH cord-014597-66vd2mdu 1284 5 VLPs vlps NN cord-014597-66vd2mdu 1284 6 productivity productivity NN cord-014597-66vd2mdu 1284 7 per per IN cord-014597-66vd2mdu 1284 8 cell cell NN cord-014597-66vd2mdu 1284 9 was be VBD cord-014597-66vd2mdu 1284 10 maintained maintain VBN cord-014597-66vd2mdu 1284 11 , , , cord-014597-66vd2mdu 1284 12 obtaining obtain VBG cord-014597-66vd2mdu 1284 13 values value NNS cord-014597-66vd2mdu 1284 14 of of IN cord-014597-66vd2mdu 1284 15 0.88 0.88 CD cord-014597-66vd2mdu 1284 16 and and CC cord-014597-66vd2mdu 1284 17 0.90 0.90 CD cord-014597-66vd2mdu 1284 18 EU.10 EU.10 NNS cord-014597-66vd2mdu 1284 19 6 6 CD cord-014597-66vd2mdu 1284 20 cells cell NNS cord-014597-66vd2mdu 1284 21 -1 -1 . cord-014597-66vd2mdu 1284 22 .day .day . cord-014597-66vd2mdu 1285 1 -1 -1 . cord-014597-66vd2mdu 1286 1 for for IN cord-014597-66vd2mdu 1286 2 the the DT cord-014597-66vd2mdu 1286 3 clone clone NN cord-014597-66vd2mdu 1286 4 being be VBG cord-014597-66vd2mdu 1286 5 cultured culture VBN cord-014597-66vd2mdu 1286 6 in in IN cord-014597-66vd2mdu 1286 7 SFM SFM NNP cord-014597-66vd2mdu 1286 8 and and CC cord-014597-66vd2mdu 1286 9 RVPM RVPM NNP cord-014597-66vd2mdu 1286 10 , , , cord-014597-66vd2mdu 1286 11 respectively respectively RB cord-014597-66vd2mdu 1286 12 . . . cord-014597-66vd2mdu 1287 1 Taking take VBG cord-014597-66vd2mdu 1287 2 into into IN cord-014597-66vd2mdu 1287 3 account account NN cord-014597-66vd2mdu 1287 4 that that IN cord-014597-66vd2mdu 1287 5 this this DT cord-014597-66vd2mdu 1287 6 producer producer NN cord-014597-66vd2mdu 1287 7 clone clone NN cord-014597-66vd2mdu 1287 8 can can MD cord-014597-66vd2mdu 1287 9 be be VB cord-014597-66vd2mdu 1287 10 changed change VBN cord-014597-66vd2mdu 1287 11 directly directly RB cord-014597-66vd2mdu 1287 12 from from IN cord-014597-66vd2mdu 1287 13 one one CD cord-014597-66vd2mdu 1287 14 medium medium NN cord-014597-66vd2mdu 1287 15 to to IN cord-014597-66vd2mdu 1287 16 the the DT cord-014597-66vd2mdu 1287 17 other other JJ cord-014597-66vd2mdu 1287 18 without without IN cord-014597-66vd2mdu 1287 19 lag lag NN cord-014597-66vd2mdu 1287 20 phase phase NN cord-014597-66vd2mdu 1287 21 or or CC cord-014597-66vd2mdu 1287 22 cell cell NN cord-014597-66vd2mdu 1287 23 damage damage NN cord-014597-66vd2mdu 1287 24 , , , cord-014597-66vd2mdu 1287 25 and and CC cord-014597-66vd2mdu 1287 26 that that IN cord-014597-66vd2mdu 1287 27 in in IN cord-014597-66vd2mdu 1287 28 RVPM RVPM NNP cord-014597-66vd2mdu 1287 29 the the DT cord-014597-66vd2mdu 1287 30 maximum maximum JJ cord-014597-66vd2mdu 1287 31 cell cell NN cord-014597-66vd2mdu 1287 32 density density NN cord-014597-66vd2mdu 1287 33 reached reach VBN cord-014597-66vd2mdu 1287 34 was be VBD cord-014597-66vd2mdu 1287 35 lower low JJR cord-014597-66vd2mdu 1287 36 , , , cord-014597-66vd2mdu 1287 37 this this DT cord-014597-66vd2mdu 1287 38 medium medium NN cord-014597-66vd2mdu 1287 39 was be VBD cord-014597-66vd2mdu 1287 40 proposed propose VBN cord-014597-66vd2mdu 1287 41 to to TO cord-014597-66vd2mdu 1287 42 be be VB cord-014597-66vd2mdu 1287 43 analysed analyse VBN cord-014597-66vd2mdu 1287 44 in in IN cord-014597-66vd2mdu 1287 45 high high JJ cord-014597-66vd2mdu 1287 46 cell cell NN cord-014597-66vd2mdu 1287 47 density density NN cord-014597-66vd2mdu 1287 48 in in IN cord-014597-66vd2mdu 1287 49 perfusion perfusion NN cord-014597-66vd2mdu 1287 50 mode mode NN cord-014597-66vd2mdu 1287 51 for for IN cord-014597-66vd2mdu 1287 52 a a DT cord-014597-66vd2mdu 1287 53 continuous continuous JJ cord-014597-66vd2mdu 1287 54 culture culture NN cord-014597-66vd2mdu 1287 55 in in IN cord-014597-66vd2mdu 1287 56 bioreactor bioreactor NN cord-014597-66vd2mdu 1287 57 . . . cord-014597-66vd2mdu 1288 1 Therefore therefore RB cord-014597-66vd2mdu 1288 2 , , , cord-014597-66vd2mdu 1288 3 we -PRON- PRP cord-014597-66vd2mdu 1288 4 performed perform VBD cord-014597-66vd2mdu 1288 5 two two CD cord-014597-66vd2mdu 1288 6 cultures culture NNS cord-014597-66vd2mdu 1288 7 in in IN cord-014597-66vd2mdu 1288 8 parallel parallel NN cord-014597-66vd2mdu 1288 9 to to TO cord-014597-66vd2mdu 1288 10 compare compare VB cord-014597-66vd2mdu 1288 11 the the DT cord-014597-66vd2mdu 1288 12 efficacy efficacy NN cord-014597-66vd2mdu 1288 13 of of IN cord-014597-66vd2mdu 1288 14 each each DT cord-014597-66vd2mdu 1288 15 media medium NNS cord-014597-66vd2mdu 1288 16 formulation formulation NN cord-014597-66vd2mdu 1288 17 in in IN cord-014597-66vd2mdu 1288 18 perfusion perfusion NN cord-014597-66vd2mdu 1288 19 . . . cord-014597-66vd2mdu 1289 1 As as IN cord-014597-66vd2mdu 1289 2 shown show VBN cord-014597-66vd2mdu 1289 3 in in IN cord-014597-66vd2mdu 1289 4 Fig Fig NNP cord-014597-66vd2mdu 1289 5 . . . cord-014597-66vd2mdu 1290 1 1 1 LS cord-014597-66vd2mdu 1290 2 , , , cord-014597-66vd2mdu 1290 3 we -PRON- PRP cord-014597-66vd2mdu 1290 4 obtained obtain VBD cord-014597-66vd2mdu 1290 5 very very RB cord-014597-66vd2mdu 1290 6 similar similar JJ cord-014597-66vd2mdu 1290 7 culture culture NN cord-014597-66vd2mdu 1290 8 performances performance NNS cord-014597-66vd2mdu 1290 9 in in IN cord-014597-66vd2mdu 1290 10 both both DT cord-014597-66vd2mdu 1290 11 bioreactors bioreactor NNS cord-014597-66vd2mdu 1290 12 ; ; : cord-014597-66vd2mdu 1290 13 14.4 14.4 CD cord-014597-66vd2mdu 1290 14 EU.ml eu.ml NN cord-014597-66vd2mdu 1290 15 -1 -1 NN cord-014597-66vd2mdu 1290 16 and and CC cord-014597-66vd2mdu 1290 17 16.1 16.1 CD cord-014597-66vd2mdu 1290 18 EU.ml EU.ml NNP cord-014597-66vd2mdu 1290 19 -1 -1 NN cord-014597-66vd2mdu 1290 20 of of IN cord-014597-66vd2mdu 1290 21 RV rv NN cord-014597-66vd2mdu 1290 22 - - HYPH cord-014597-66vd2mdu 1290 23 VLPs vlp NNS cord-014597-66vd2mdu 1290 24 for for IN cord-014597-66vd2mdu 1290 25 the the DT cord-014597-66vd2mdu 1290 26 commercial commercial JJ cord-014597-66vd2mdu 1290 27 SFM SFM NNP cord-014597-66vd2mdu 1290 28 and and CC cord-014597-66vd2mdu 1290 29 RVPM RVPM NNP cord-014597-66vd2mdu 1290 30 , , , cord-014597-66vd2mdu 1290 31 respectively respectively RB cord-014597-66vd2mdu 1290 32 . . . cord-014597-66vd2mdu 1291 1 After after IN cord-014597-66vd2mdu 1291 2 that that DT cord-014597-66vd2mdu 1291 3 , , , cord-014597-66vd2mdu 1291 4 the the DT cord-014597-66vd2mdu 1291 5 harvests harvest NNS cord-014597-66vd2mdu 1291 6 were be VBD cord-014597-66vd2mdu 1291 7 evaluated evaluate VBN cord-014597-66vd2mdu 1291 8 by by IN cord-014597-66vd2mdu 1291 9 the the DT cord-014597-66vd2mdu 1291 10 NIH NIH NNP cord-014597-66vd2mdu 1291 11 potency potency NN cord-014597-66vd2mdu 1291 12 test test NN cord-014597-66vd2mdu 1291 13 obtaining obtain VBG cord-014597-66vd2mdu 1291 14 a a DT cord-014597-66vd2mdu 1291 15 rabies rabies NN cord-014597-66vd2mdu 1291 16 vaccine vaccine NN cord-014597-66vd2mdu 1291 17 potency potency NN cord-014597-66vd2mdu 1291 18 of of IN cord-014597-66vd2mdu 1291 19 1.2 1.2 CD cord-014597-66vd2mdu 1291 20 IU.ml IU.ml NNP cord-014597-66vd2mdu 1291 21 -1 -1 . cord-014597-66vd2mdu 1292 1 for for IN cord-014597-66vd2mdu 1292 2 both both DT cord-014597-66vd2mdu 1292 3 cultures culture NNS cord-014597-66vd2mdu 1292 4 ( ( -LRB- cord-014597-66vd2mdu 1292 5 being be VBG cord-014597-66vd2mdu 1292 6 1 1 CD cord-014597-66vd2mdu 1293 1 IU.ml IU.ml NNP cord-014597-66vd2mdu 1293 2 -1 -1 . cord-014597-66vd2mdu 1294 1 the the DT cord-014597-66vd2mdu 1294 2 minimum minimum JJ cord-014597-66vd2mdu 1294 3 potency potency NN cord-014597-66vd2mdu 1294 4 required require VBN cord-014597-66vd2mdu 1294 5 for for IN cord-014597-66vd2mdu 1294 6 animal animal NN cord-014597-66vd2mdu 1294 7 vaccine vaccine NN cord-014597-66vd2mdu 1294 8 ) ) -RRB- cord-014597-66vd2mdu 1294 9 . . . cord-014597-66vd2mdu 1295 1 Thus thus RB cord-014597-66vd2mdu 1295 2 , , , cord-014597-66vd2mdu 1295 3 the the DT cord-014597-66vd2mdu 1295 4 results result NNS cord-014597-66vd2mdu 1295 5 obtained obtain VBD cord-014597-66vd2mdu 1295 6 represent represent VBP cord-014597-66vd2mdu 1295 7 an an DT cord-014597-66vd2mdu 1295 8 interesting interesting JJ cord-014597-66vd2mdu 1295 9 advance advance NN cord-014597-66vd2mdu 1295 10 in in IN cord-014597-66vd2mdu 1295 11 the the DT cord-014597-66vd2mdu 1295 12 optimization optimization NN cord-014597-66vd2mdu 1295 13 of of IN cord-014597-66vd2mdu 1295 14 this this DT cord-014597-66vd2mdu 1295 15 vaccine vaccine NN cord-014597-66vd2mdu 1295 16 production production NN cord-014597-66vd2mdu 1295 17 process process NN cord-014597-66vd2mdu 1295 18 since since IN cord-014597-66vd2mdu 1295 19 the the DT cord-014597-66vd2mdu 1295 20 use use NN cord-014597-66vd2mdu 1295 21 of of IN cord-014597-66vd2mdu 1295 22 this this DT cord-014597-66vd2mdu 1295 23 new new JJ cord-014597-66vd2mdu 1295 24 medium medium JJ cord-014597-66vd2mdu 1295 25 formulation formulation NN cord-014597-66vd2mdu 1295 26 represents represent VBZ cord-014597-66vd2mdu 1295 27 a a DT cord-014597-66vd2mdu 1295 28 reduction reduction NN cord-014597-66vd2mdu 1295 29 of of IN cord-014597-66vd2mdu 1295 30 40 40 CD cord-014597-66vd2mdu 1295 31 % % NN cord-014597-66vd2mdu 1295 32 of of IN cord-014597-66vd2mdu 1295 33 the the DT cord-014597-66vd2mdu 1295 34 total total JJ cord-014597-66vd2mdu 1295 35 cost cost NN cord-014597-66vd2mdu 1295 36 which which WDT cord-014597-66vd2mdu 1295 37 will will MD cord-014597-66vd2mdu 1295 38 be be VB cord-014597-66vd2mdu 1295 39 reflected reflect VBN cord-014597-66vd2mdu 1295 40 in in IN cord-014597-66vd2mdu 1295 41 a a DT cord-014597-66vd2mdu 1295 42 considerable considerable JJ cord-014597-66vd2mdu 1295 43 reduction reduction NN cord-014597-66vd2mdu 1295 44 of of IN cord-014597-66vd2mdu 1295 45 the the DT cord-014597-66vd2mdu 1295 46 price price NN cord-014597-66vd2mdu 1295 47 of of IN cord-014597-66vd2mdu 1295 48 the the DT cord-014597-66vd2mdu 1295 49 vaccine vaccine NN cord-014597-66vd2mdu 1295 50 dose dose NN cord-014597-66vd2mdu 1295 51 . . . cord-014597-66vd2mdu 1296 1 Background background NN cord-014597-66vd2mdu 1296 2 Vaccines vaccine NNS cord-014597-66vd2mdu 1296 3 are be VBP cord-014597-66vd2mdu 1296 4 one one CD cord-014597-66vd2mdu 1296 5 of of IN cord-014597-66vd2mdu 1296 6 the the DT cord-014597-66vd2mdu 1296 7 most most RBS cord-014597-66vd2mdu 1296 8 powerful powerful JJ cord-014597-66vd2mdu 1296 9 and and CC cord-014597-66vd2mdu 1296 10 effective effective JJ cord-014597-66vd2mdu 1296 11 health health NN cord-014597-66vd2mdu 1296 12 inventions invention NNS cord-014597-66vd2mdu 1296 13 ever ever RB cord-014597-66vd2mdu 1296 14 developedproviding developedprovide VBG cord-014597-66vd2mdu 1296 15 tremendous tremendous JJ cord-014597-66vd2mdu 1296 16 economic economic JJ cord-014597-66vd2mdu 1296 17 and and CC cord-014597-66vd2mdu 1296 18 societal societal JJ cord-014597-66vd2mdu 1296 19 value value NN cord-014597-66vd2mdu 1296 20 ; ; : cord-014597-66vd2mdu 1296 21 yet yet CC cord-014597-66vd2mdu 1296 22 several several JJ cord-014597-66vd2mdu 1296 23 factors factor NNS cord-014597-66vd2mdu 1296 24 hinder hinder VBP cord-014597-66vd2mdu 1296 25 comprehensive comprehensive JJ cord-014597-66vd2mdu 1296 26 immunization immunization NN cord-014597-66vd2mdu 1296 27 coverage coverage NN cord-014597-66vd2mdu 1296 28 . . . cord-014597-66vd2mdu 1297 1 Traditional traditional JJ cord-014597-66vd2mdu 1297 2 methods method NNS cord-014597-66vd2mdu 1297 3 of of IN cord-014597-66vd2mdu 1297 4 biologics biologic NNS cord-014597-66vd2mdu 1297 5 production production NN cord-014597-66vd2mdu 1297 6 , , , cord-014597-66vd2mdu 1297 7 based base VBN cord-014597-66vd2mdu 1297 8 on on IN cord-014597-66vd2mdu 1297 9 stainless stainless JJ cord-014597-66vd2mdu 1297 10 steel steel NN cord-014597-66vd2mdu 1297 11 bioreactors bioreactor NNS cord-014597-66vd2mdu 1297 12 , , , cord-014597-66vd2mdu 1297 13 allow allow VB cord-014597-66vd2mdu 1297 14 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 1297 15 companies company NNS cord-014597-66vd2mdu 1297 16 to to TO cord-014597-66vd2mdu 1297 17 achieve achieve VB cord-014597-66vd2mdu 1297 18 economy economy NN cord-014597-66vd2mdu 1297 19 of of IN cord-014597-66vd2mdu 1297 20 scale scale NN cord-014597-66vd2mdu 1297 21 , , , cord-014597-66vd2mdu 1297 22 but but CC cord-014597-66vd2mdu 1297 23 are be VBP cord-014597-66vd2mdu 1297 24 limited limit VBN cord-014597-66vd2mdu 1297 25 by by IN cord-014597-66vd2mdu 1297 26 high high JJ cord-014597-66vd2mdu 1297 27 capital capital NN cord-014597-66vd2mdu 1297 28 expenditures expenditure NNS cord-014597-66vd2mdu 1297 29 . . . cord-014597-66vd2mdu 1298 1 Such such JJ cord-014597-66vd2mdu 1298 2 approaches approach NNS cord-014597-66vd2mdu 1298 3 stifle stifle VBP cord-014597-66vd2mdu 1298 4 manufacturing manufacture VBG cord-014597-66vd2mdu 1298 5 innovation innovation NN cord-014597-66vd2mdu 1298 6 and and CC cord-014597-66vd2mdu 1298 7 lack lack JJ cord-014597-66vd2mdu 1298 8 long long JJ cord-014597-66vd2mdu 1298 9 - - HYPH cord-014597-66vd2mdu 1298 10 term term NN cord-014597-66vd2mdu 1298 11 cost cost NN cord-014597-66vd2mdu 1298 12 - - HYPH cord-014597-66vd2mdu 1298 13 effectiveness effectiveness NN cord-014597-66vd2mdu 1298 14 and and CC cord-014597-66vd2mdu 1298 15 sustainability sustainability NN cord-014597-66vd2mdu 1298 16 . . . cord-014597-66vd2mdu 1299 1 Current current JJ cord-014597-66vd2mdu 1299 2 innovations innovation NNS cord-014597-66vd2mdu 1299 3 can can MD cord-014597-66vd2mdu 1299 4 cut cut VB cord-014597-66vd2mdu 1299 5 biologics biologic NNS cord-014597-66vd2mdu 1299 6 ' ' POS cord-014597-66vd2mdu 1299 7 production production NN cord-014597-66vd2mdu 1299 8 costs cost NNS cord-014597-66vd2mdu 1299 9 to to TO cord-014597-66vd2mdu 1299 10 revolutionize revolutionize VB cord-014597-66vd2mdu 1299 11 the the DT cord-014597-66vd2mdu 1299 12 mainstream mainstream NN cord-014597-66vd2mdu 1299 13 use use NN cord-014597-66vd2mdu 1299 14 of of IN cord-014597-66vd2mdu 1299 15 biologic biologic JJ cord-014597-66vd2mdu 1299 16 treatments treatment NNS cord-014597-66vd2mdu 1299 17 , , , cord-014597-66vd2mdu 1299 18 focusing focus VBG cord-014597-66vd2mdu 1299 19 on on IN cord-014597-66vd2mdu 1299 20 developing develop VBG cord-014597-66vd2mdu 1299 21 fast fast RB cord-014597-66vd2mdu 1299 22 , , , cord-014597-66vd2mdu 1299 23 potent potent JJ cord-014597-66vd2mdu 1299 24 and and CC cord-014597-66vd2mdu 1299 25 cost cost NN cord-014597-66vd2mdu 1299 26 - - HYPH cord-014597-66vd2mdu 1299 27 effective effective JJ cord-014597-66vd2mdu 1299 28 vaccine vaccine NN cord-014597-66vd2mdu 1299 29 production production NN cord-014597-66vd2mdu 1299 30 . . . cord-014597-66vd2mdu 1300 1 Univercells Univercells NNP cord-014597-66vd2mdu 1300 2 ' ' POS cord-014597-66vd2mdu 1300 3 mission mission NN cord-014597-66vd2mdu 1300 4 to to TO cord-014597-66vd2mdu 1300 5 make make VB cord-014597-66vd2mdu 1300 6 biologics biologic NNS cord-014597-66vd2mdu 1300 7 affordable affordable JJ cord-014597-66vd2mdu 1300 8 to to IN cord-014597-66vd2mdu 1300 9 all all DT cord-014597-66vd2mdu 1300 10 initiated initiate VBN cord-014597-66vd2mdu 1300 11 a a DT cord-014597-66vd2mdu 1300 12 paradigm paradigm NN cord-014597-66vd2mdu 1300 13 shift shift NN cord-014597-66vd2mdu 1300 14 , , , cord-014597-66vd2mdu 1300 15 targeting target VBG cord-014597-66vd2mdu 1300 16 an an DT cord-014597-66vd2mdu 1300 17 innovative innovative JJ cord-014597-66vd2mdu 1300 18 single single JJ cord-014597-66vd2mdu 1300 19 - - HYPH cord-014597-66vd2mdu 1300 20 use use NN cord-014597-66vd2mdu 1300 21 manufacturing manufacturing NN cord-014597-66vd2mdu 1300 22 platform platform NN cord-014597-66vd2mdu 1300 23 incorporating incorporate VBG cord-014597-66vd2mdu 1300 24 bioprocess bioprocess NN cord-014597-66vd2mdu 1300 25 into into IN cord-014597-66vd2mdu 1300 26 continuous continuous JJ cord-014597-66vd2mdu 1300 27 operations operation NNS cord-014597-66vd2mdu 1300 28 . . . cord-014597-66vd2mdu 1301 1 Univercells Univercells NNP cord-014597-66vd2mdu 1301 2 employs employ VBZ cord-014597-66vd2mdu 1301 3 process process NN cord-014597-66vd2mdu 1301 4 intensification intensification NN cord-014597-66vd2mdu 1301 5 , , , cord-014597-66vd2mdu 1301 6 using use VBG cord-014597-66vd2mdu 1301 7 high high JJ cord-014597-66vd2mdu 1301 8 volumetric volumetric JJ cord-014597-66vd2mdu 1301 9 productivity productivity NN cord-014597-66vd2mdu 1301 10 bioreactors bioreactor NNS cord-014597-66vd2mdu 1301 11 ; ; : cord-014597-66vd2mdu 1301 12 and and CC cord-014597-66vd2mdu 1301 13 unit unit NN cord-014597-66vd2mdu 1301 14 steps step NNS cord-014597-66vd2mdu 1301 15 integration integration NN cord-014597-66vd2mdu 1301 16 , , , cord-014597-66vd2mdu 1301 17 coupling couple VBG cord-014597-66vd2mdu 1301 18 USP USP NNP cord-014597-66vd2mdu 1301 19 and and CC cord-014597-66vd2mdu 1301 20 DSP DSP NNP cord-014597-66vd2mdu 1301 21 into into IN cord-014597-66vd2mdu 1301 22 continuous continuous JJ cord-014597-66vd2mdu 1301 23 operations operation NNS cord-014597-66vd2mdu 1301 24 . . . cord-014597-66vd2mdu 1302 1 The the DT cord-014597-66vd2mdu 1302 2 objective objective NN cord-014597-66vd2mdu 1302 3 is be VBZ cord-014597-66vd2mdu 1302 4 a a DT cord-014597-66vd2mdu 1302 5 down down RB cord-014597-66vd2mdu 1302 6 - - HYPH cord-014597-66vd2mdu 1302 7 scaled scale VBN cord-014597-66vd2mdu 1302 8 high high JJ cord-014597-66vd2mdu 1302 9 - - HYPH cord-014597-66vd2mdu 1302 10 productivity productivity NN cord-014597-66vd2mdu 1302 11 process process NN cord-014597-66vd2mdu 1302 12 for for IN cord-014597-66vd2mdu 1302 13 a a DT cord-014597-66vd2mdu 1302 14 cost cost NN cord-014597-66vd2mdu 1302 15 - - HYPH cord-014597-66vd2mdu 1302 16 effective effective JJ cord-014597-66vd2mdu 1302 17 manufacturing manufacturing NN cord-014597-66vd2mdu 1302 18 solution solution NN cord-014597-66vd2mdu 1302 19 . . . cord-014597-66vd2mdu 1303 1 The the DT cord-014597-66vd2mdu 1303 2 resulting result VBG cord-014597-66vd2mdu 1303 3 micro micro NN cord-014597-66vd2mdu 1303 4 - - NNS cord-014597-66vd2mdu 1303 5 facilities facility NNS cord-014597-66vd2mdu 1303 6 are be VBP cord-014597-66vd2mdu 1303 7 easily easily RB cord-014597-66vd2mdu 1303 8 - - HYPH cord-014597-66vd2mdu 1303 9 deployable deployable JJ cord-014597-66vd2mdu 1303 10 in in IN cord-014597-66vd2mdu 1303 11 developing develop VBG cord-014597-66vd2mdu 1303 12 countries country NNS cord-014597-66vd2mdu 1303 13 , , , cord-014597-66vd2mdu 1303 14 breaking break VBG cord-014597-66vd2mdu 1303 15 entry entry NN cord-014597-66vd2mdu 1303 16 barriers barrier NNS cord-014597-66vd2mdu 1303 17 to to IN cord-014597-66vd2mdu 1303 18 biomanufacturing biomanufacture VBG cord-014597-66vd2mdu 1303 19 ( ( -LRB- cord-014597-66vd2mdu 1303 20 Fig Fig NNP cord-014597-66vd2mdu 1303 21 . . . cord-014597-66vd2mdu 1303 22 1 1 CD cord-014597-66vd2mdu 1303 23 ) ) -RRB- cord-014597-66vd2mdu 1303 24 . . . cord-014597-66vd2mdu 1304 1 Manufacturing manufacturing NN cord-014597-66vd2mdu 1304 2 and and CC cord-014597-66vd2mdu 1304 3 distribution distribution NN cord-014597-66vd2mdu 1304 4 advancements advancement NNS cord-014597-66vd2mdu 1304 5 , , , cord-014597-66vd2mdu 1304 6 from from IN cord-014597-66vd2mdu 1304 7 centralized centralize VBN cord-014597-66vd2mdu 1304 8 to to IN cord-014597-66vd2mdu 1304 9 distributed distribute VBN cord-014597-66vd2mdu 1304 10 , , , cord-014597-66vd2mdu 1304 11 foresee foresee VB cord-014597-66vd2mdu 1304 12 affordable affordable JJ cord-014597-66vd2mdu 1304 13 treatments treatment NNS cord-014597-66vd2mdu 1304 14 ' ' POS cord-014597-66vd2mdu 1304 15 obtainability obtainability NN cord-014597-66vd2mdu 1304 16 via via IN cord-014597-66vd2mdu 1304 17 supplying supply VBG cord-014597-66vd2mdu 1304 18 local local JJ cord-014597-66vd2mdu 1304 19 populations population NNS cord-014597-66vd2mdu 1304 20 with with IN cord-014597-66vd2mdu 1304 21 local local JJ cord-014597-66vd2mdu 1304 22 production production NN cord-014597-66vd2mdu 1304 23 units unit NNS cord-014597-66vd2mdu 1304 24 . . . cord-014597-66vd2mdu 1305 1 -Bench -bench LS cord-014597-66vd2mdu 1305 2 - - HYPH cord-014597-66vd2mdu 1305 3 scale scale NN cord-014597-66vd2mdu 1305 4 fixed fix VBN cord-014597-66vd2mdu 1305 5 - - HYPH cord-014597-66vd2mdu 1305 6 bed bed NN cord-014597-66vd2mdu 1305 7 bioreactor bioreactor NN cord-014597-66vd2mdu 1305 8 ; ; : cord-014597-66vd2mdu 1305 9 -Carriers -Carriers : cord-014597-66vd2mdu 1305 10 made make VBN cord-014597-66vd2mdu 1305 11 of of IN cord-014597-66vd2mdu 1305 12 100 100 CD cord-014597-66vd2mdu 1305 13 % % NN cord-014597-66vd2mdu 1305 14 pure pure JJ cord-014597-66vd2mdu 1305 15 non non JJ cord-014597-66vd2mdu 1305 16 - - JJ cord-014597-66vd2mdu 1305 17 woven woven JJ cord-014597-66vd2mdu 1305 18 hydrophilized hydrophilized JJ cord-014597-66vd2mdu 1305 19 PET pet JJ cord-014597-66vd2mdu 1305 20 fibers fiber NNS cord-014597-66vd2mdu 1305 21 ; ; : cord-014597-66vd2mdu 1305 22 -Vero -vero CD cord-014597-66vd2mdu 1305 23 cells cell NNS cord-014597-66vd2mdu 1305 24 grown grow VBN cord-014597-66vd2mdu 1305 25 in in IN cord-014597-66vd2mdu 1305 26 serum serum NN cord-014597-66vd2mdu 1305 27 - - HYPH cord-014597-66vd2mdu 1305 28 free free JJ cord-014597-66vd2mdu 1305 29 and and CC cord-014597-66vd2mdu 1305 30 serum serum NN cord-014597-66vd2mdu 1305 31 containing contain VBG cord-014597-66vd2mdu 1305 32 media medium NNS cord-014597-66vd2mdu 1305 33 ; ; , cord-014597-66vd2mdu 1305 34 -Attenuated -attenuate VBD cord-014597-66vd2mdu 1305 35 polio polio NN cord-014597-66vd2mdu 1305 36 strains strain NNS cord-014597-66vd2mdu 1305 37 ; ; : cord-014597-66vd2mdu 1306 1 -Cell -Cell NFP cord-014597-66vd2mdu 1306 2 nuclei nucleus NNS cord-014597-66vd2mdu 1306 3 on on IN cord-014597-66vd2mdu 1306 4 carriers carrier NNS cord-014597-66vd2mdu 1306 5 counted count VBN cord-014597-66vd2mdu 1306 6 by by IN cord-014597-66vd2mdu 1306 7 the the DT cord-014597-66vd2mdu 1306 8 crystal crystal NN cord-014597-66vd2mdu 1306 9 violet violet NN cord-014597-66vd2mdu 1306 10 method method NN cord-014597-66vd2mdu 1306 11 ; ; : cord-014597-66vd2mdu 1306 12 -Polio -polio WDT cord-014597-66vd2mdu 1306 13 virus virus NN cord-014597-66vd2mdu 1306 14 production production NN cord-014597-66vd2mdu 1306 15 estimated estimate VBN cord-014597-66vd2mdu 1306 16 by by IN cord-014597-66vd2mdu 1306 17 Elisa Elisa NNP cord-014597-66vd2mdu 1306 18 assay assay NN cord-014597-66vd2mdu 1306 19 ( ( -LRB- cord-014597-66vd2mdu 1306 20 D d NN cord-014597-66vd2mdu 1306 21 - - HYPH cord-014597-66vd2mdu 1306 22 antigen antigen NN cord-014597-66vd2mdu 1306 23 content content NN cord-014597-66vd2mdu 1306 24 ) ) -RRB- cord-014597-66vd2mdu 1306 25 . . . cord-014597-66vd2mdu 1307 1 Cultivation cultivation NN cord-014597-66vd2mdu 1307 2 of of IN cord-014597-66vd2mdu 1307 3 Vero Vero NNP cord-014597-66vd2mdu 1307 4 cells cell NNS cord-014597-66vd2mdu 1307 5 in in IN cord-014597-66vd2mdu 1307 6 medium medium NN cord-014597-66vd2mdu 1307 7 with with IN cord-014597-66vd2mdu 1307 8 serum serum NN cord-014597-66vd2mdu 1307 9 and and CC cord-014597-66vd2mdu 1307 10 in in IN cord-014597-66vd2mdu 1307 11 serum serum NN cord-014597-66vd2mdu 1307 12 - - HYPH cord-014597-66vd2mdu 1307 13 free free JJ cord-014597-66vd2mdu 1307 14 medium medium NN cord-014597-66vd2mdu 1307 15 , , , cord-014597-66vd2mdu 1307 16 was be VBD cord-014597-66vd2mdu 1307 17 carried carry VBN cord-014597-66vd2mdu 1307 18 out out RP cord-014597-66vd2mdu 1307 19 in in IN cord-014597-66vd2mdu 1307 20 bench bench NN cord-014597-66vd2mdu 1307 21 - - HYPH cord-014597-66vd2mdu 1307 22 scale scale NN cord-014597-66vd2mdu 1307 23 compact compact JJ cord-014597-66vd2mdu 1307 24 fixed fix VBN cord-014597-66vd2mdu 1307 25 - - HYPH cord-014597-66vd2mdu 1307 26 bed bed NN cord-014597-66vd2mdu 1307 27 bioreactors bioreactor NNS cord-014597-66vd2mdu 1307 28 , , , cord-014597-66vd2mdu 1307 29 to to TO cord-014597-66vd2mdu 1307 30 determine determine VB cord-014597-66vd2mdu 1307 31 which which WDT cord-014597-66vd2mdu 1307 32 culture culture NN cord-014597-66vd2mdu 1307 33 conditions condition NNS cord-014597-66vd2mdu 1307 34 result result VBP cord-014597-66vd2mdu 1307 35 in in IN cord-014597-66vd2mdu 1307 36 the the DT cord-014597-66vd2mdu 1307 37 highest high JJS cord-014597-66vd2mdu 1307 38 growth growth NN cord-014597-66vd2mdu 1307 39 rate rate NN cord-014597-66vd2mdu 1307 40 , , , cord-014597-66vd2mdu 1307 41 the the DT cord-014597-66vd2mdu 1307 42 highest high JJS cord-014597-66vd2mdu 1307 43 cell cell NN cord-014597-66vd2mdu 1307 44 biomass biomass NN cord-014597-66vd2mdu 1307 45 by by IN cord-014597-66vd2mdu 1307 46 carriers carrier NNS cord-014597-66vd2mdu 1307 47 and and CC cord-014597-66vd2mdu 1307 48 virus virus NN cord-014597-66vd2mdu 1307 49 production production NN cord-014597-66vd2mdu 1307 50 . . . cord-014597-66vd2mdu 1308 1 Cells cell NNS cord-014597-66vd2mdu 1308 2 were be VBD cord-014597-66vd2mdu 1308 3 inoculated inoculate VBN cord-014597-66vd2mdu 1308 4 at at IN cord-014597-66vd2mdu 1308 5 0.05x10 0.05x10 CD cord-014597-66vd2mdu 1308 6 6 6 CD cord-014597-66vd2mdu 1308 7 cells cell NNS cord-014597-66vd2mdu 1308 8 / / SYM cord-014597-66vd2mdu 1308 9 cm cm NN cord-014597-66vd2mdu 1308 10 2 2 CD cord-014597-66vd2mdu 1308 11 and and CC cord-014597-66vd2mdu 1308 12 infected infect VBN cord-014597-66vd2mdu 1308 13 during during IN cord-014597-66vd2mdu 1308 14 the the DT cord-014597-66vd2mdu 1308 15 mid mid JJ cord-014597-66vd2mdu 1308 16 - - JJ cord-014597-66vd2mdu 1308 17 exponential exponential JJ cord-014597-66vd2mdu 1308 18 phase phase NN cord-014597-66vd2mdu 1308 19 , , , cord-014597-66vd2mdu 1308 20 following follow VBG cord-014597-66vd2mdu 1308 21 a a DT cord-014597-66vd2mdu 1308 22 complete complete JJ cord-014597-66vd2mdu 1308 23 media media NN cord-014597-66vd2mdu 1308 24 exchange exchange NN cord-014597-66vd2mdu 1308 25 . . . cord-014597-66vd2mdu 1309 1 Viral viral JJ cord-014597-66vd2mdu 1309 2 infection infection NN cord-014597-66vd2mdu 1309 3 took take VBD cord-014597-66vd2mdu 1309 4 place place NN cord-014597-66vd2mdu 1309 5 in in IN cord-014597-66vd2mdu 1309 6 serum serum NN cord-014597-66vd2mdu 1309 7 - - HYPH cord-014597-66vd2mdu 1309 8 free free JJ cord-014597-66vd2mdu 1309 9 media medium NNS cord-014597-66vd2mdu 1309 10 . . . cord-014597-66vd2mdu 1310 1 In in IN cord-014597-66vd2mdu 1310 2 - - HYPH cord-014597-66vd2mdu 1310 3 line line NN cord-014597-66vd2mdu 1310 4 clarification clarification NN cord-014597-66vd2mdu 1310 5 and and CC cord-014597-66vd2mdu 1310 6 purification purification NN cord-014597-66vd2mdu 1310 7 is be VBZ cord-014597-66vd2mdu 1310 8 targeted target VBN cord-014597-66vd2mdu 1310 9 to to TO cord-014597-66vd2mdu 1310 10 be be VB cord-014597-66vd2mdu 1310 11 performed perform VBN cord-014597-66vd2mdu 1310 12 in in IN cord-014597-66vd2mdu 1310 13 only only RB cord-014597-66vd2mdu 1310 14 a a DT cord-014597-66vd2mdu 1310 15 few few JJ cord-014597-66vd2mdu 1310 16 steps step NNS cord-014597-66vd2mdu 1310 17 ( ( -LRB- cord-014597-66vd2mdu 1310 18 maximum maximum VB cord-014597-66vd2mdu 1310 19 one one CD cord-014597-66vd2mdu 1310 20 of of IN cord-014597-66vd2mdu 1310 21 two two CD cord-014597-66vd2mdu 1310 22 ) ) -RRB- cord-014597-66vd2mdu 1310 23 without without IN cord-014597-66vd2mdu 1310 24 intermediary intermediary JJ cord-014597-66vd2mdu 1310 25 diafiltration diafiltration NN cord-014597-66vd2mdu 1310 26 . . . cord-014597-66vd2mdu 1311 1 In in IN cord-014597-66vd2mdu 1311 2 such such JJ cord-014597-66vd2mdu 1311 3 configuration configuration NN cord-014597-66vd2mdu 1311 4 , , , cord-014597-66vd2mdu 1311 5 we -PRON- PRP cord-014597-66vd2mdu 1311 6 measured measure VBD cord-014597-66vd2mdu 1311 7 that that IN cord-014597-66vd2mdu 1311 8 Vero Vero NNP cord-014597-66vd2mdu 1311 9 cells cell NNS cord-014597-66vd2mdu 1311 10 can can MD cord-014597-66vd2mdu 1311 11 reach reach VB cord-014597-66vd2mdu 1311 12 a a DT cord-014597-66vd2mdu 1311 13 cell cell NN cord-014597-66vd2mdu 1311 14 density density NN cord-014597-66vd2mdu 1311 15 of of IN cord-014597-66vd2mdu 1311 16 300 300 CD cord-014597-66vd2mdu 1311 17 - - SYM cord-014597-66vd2mdu 1311 18 350x10 350x10 CD cord-014597-66vd2mdu 1311 19 3 3 CD cord-014597-66vd2mdu 1311 20 cells cell NNS cord-014597-66vd2mdu 1311 21 / / SYM cord-014597-66vd2mdu 1311 22 cm cm NN cord-014597-66vd2mdu 1311 23 2 2 CD cord-014597-66vd2mdu 1311 24 with with IN cord-014597-66vd2mdu 1311 25 PDL PDL NNP cord-014597-66vd2mdu 1311 26 / / SYM cord-014597-66vd2mdu 1311 27 day day NN cord-014597-66vd2mdu 1311 28 of of IN cord-014597-66vd2mdu 1311 29 1.0 1.0 CD cord-014597-66vd2mdu 1311 30 - - SYM cord-014597-66vd2mdu 1311 31 1.2 1.2 CD cord-014597-66vd2mdu 1311 32 in in IN cord-014597-66vd2mdu 1311 33 serum serum NN cord-014597-66vd2mdu 1311 34 - - HYPH cord-014597-66vd2mdu 1311 35 containing contain VBG cord-014597-66vd2mdu 1311 36 media medium NNS cord-014597-66vd2mdu 1311 37 . . . cord-014597-66vd2mdu 1312 1 This this DT cord-014597-66vd2mdu 1312 2 new new JJ cord-014597-66vd2mdu 1312 3 facility facility NN cord-014597-66vd2mdu 1312 4 is be VBZ cord-014597-66vd2mdu 1312 5 expected expect VBN cord-014597-66vd2mdu 1312 6 to to TO cord-014597-66vd2mdu 1312 7 manufacture manufacture VB cord-014597-66vd2mdu 1312 8 any any DT cord-014597-66vd2mdu 1312 9 type type NN cord-014597-66vd2mdu 1312 10 of of IN cord-014597-66vd2mdu 1312 11 viral viral JJ cord-014597-66vd2mdu 1312 12 vaccine vaccine NN cord-014597-66vd2mdu 1312 13 at at IN cord-014597-66vd2mdu 1312 14 a a DT cord-014597-66vd2mdu 1312 15 very very RB cord-014597-66vd2mdu 1312 16 low low JJ cord-014597-66vd2mdu 1312 17 cost cost NN cord-014597-66vd2mdu 1312 18 and and CC cord-014597-66vd2mdu 1312 19 could could MD cord-014597-66vd2mdu 1312 20 be be VB cord-014597-66vd2mdu 1312 21 deployed deploy VBN cord-014597-66vd2mdu 1312 22 at at IN cord-014597-66vd2mdu 1312 23 the the DT cord-014597-66vd2mdu 1312 24 site site NN cord-014597-66vd2mdu 1312 25 of of IN cord-014597-66vd2mdu 1312 26 the the DT cord-014597-66vd2mdu 1312 27 manufacturer manufacturer NN cord-014597-66vd2mdu 1312 28 in in IN cord-014597-66vd2mdu 1312 29 emerging emerge VBG cord-014597-66vd2mdu 1312 30 countries country NNS cord-014597-66vd2mdu 1312 31 , , , cord-014597-66vd2mdu 1312 32 killing kill VBG cord-014597-66vd2mdu 1312 33 the the DT cord-014597-66vd2mdu 1312 34 two two CD cord-014597-66vd2mdu 1312 35 birds bird NNS cord-014597-66vd2mdu 1312 36 of of IN cord-014597-66vd2mdu 1312 37 cost cost NN cord-014597-66vd2mdu 1312 38 of of IN cord-014597-66vd2mdu 1312 39 manufacturing manufacturing NN cord-014597-66vd2mdu 1312 40 and and CC cord-014597-66vd2mdu 1312 41 distribution distribution NN cord-014597-66vd2mdu 1312 42 with with IN cord-014597-66vd2mdu 1312 43 one one CD cord-014597-66vd2mdu 1312 44 stone stone NN cord-014597-66vd2mdu 1312 45 . . . cord-014597-66vd2mdu 1313 1 The the DT cord-014597-66vd2mdu 1313 2 presentation presentation NN cord-014597-66vd2mdu 1313 3 will will MD cord-014597-66vd2mdu 1313 4 feature feature VB cord-014597-66vd2mdu 1313 5 the the DT cord-014597-66vd2mdu 1313 6 description description NN cord-014597-66vd2mdu 1313 7 of of IN cord-014597-66vd2mdu 1313 8 the the DT cord-014597-66vd2mdu 1313 9 engineering engineering NN cord-014597-66vd2mdu 1313 10 development development NN cord-014597-66vd2mdu 1313 11 , , , cord-014597-66vd2mdu 1313 12 but but CC cord-014597-66vd2mdu 1313 13 also also RB cord-014597-66vd2mdu 1313 14 the the DT cord-014597-66vd2mdu 1313 15 preliminary preliminary JJ cord-014597-66vd2mdu 1313 16 results result NNS cord-014597-66vd2mdu 1313 17 of of IN cord-014597-66vd2mdu 1313 18 cell cell NN cord-014597-66vd2mdu 1313 19 growth growth NN cord-014597-66vd2mdu 1313 20 , , , cord-014597-66vd2mdu 1313 21 infections infection NNS cord-014597-66vd2mdu 1313 22 , , , cord-014597-66vd2mdu 1313 23 and and CC cord-014597-66vd2mdu 1313 24 product product NN cord-014597-66vd2mdu 1313 25 quality quality NN cord-014597-66vd2mdu 1313 26 , , , cord-014597-66vd2mdu 1313 27 as as RB cord-014597-66vd2mdu 1313 28 well well RB cord-014597-66vd2mdu 1313 29 as as IN cord-014597-66vd2mdu 1313 30 a a DT cord-014597-66vd2mdu 1313 31 description description NN cord-014597-66vd2mdu 1313 32 of of IN cord-014597-66vd2mdu 1313 33 the the DT cord-014597-66vd2mdu 1313 34 COGS cogs JJ cord-014597-66vd2mdu 1313 35 calculation calculation NN cord-014597-66vd2mdu 1313 36 . . . cord-014597-66vd2mdu 1314 1 Univercells Univercells NNP cord-014597-66vd2mdu 1314 2 developed develop VBD cord-014597-66vd2mdu 1314 3 a a DT cord-014597-66vd2mdu 1314 4 disruptive disruptive JJ cord-014597-66vd2mdu 1314 5 polio polio NN cord-014597-66vd2mdu 1314 6 vaccine vaccine NN cord-014597-66vd2mdu 1314 7 manufacturing manufacturing NN cord-014597-66vd2mdu 1314 8 technology technology NN cord-014597-66vd2mdu 1314 9 exceeding exceed VBG cord-014597-66vd2mdu 1314 10 expectations expectation NNS cord-014597-66vd2mdu 1314 11 when when WRB cord-014597-66vd2mdu 1314 12 compared compare VBN cord-014597-66vd2mdu 1314 13 to to IN cord-014597-66vd2mdu 1314 14 traditional traditional JJ cord-014597-66vd2mdu 1314 15 methodsachieving methodsachieving NN cord-014597-66vd2mdu 1314 16 a a DT cord-014597-66vd2mdu 1314 17 superior superior JJ cord-014597-66vd2mdu 1314 18 result result NN cord-014597-66vd2mdu 1314 19 via via IN cord-014597-66vd2mdu 1314 20 its -PRON- PRP$ cord-014597-66vd2mdu 1314 21 all all DT cord-014597-66vd2mdu 1314 22 - - HYPH cord-014597-66vd2mdu 1314 23 in in IN cord-014597-66vd2mdu 1314 24 - - HYPH cord-014597-66vd2mdu 1314 25 one one CD cord-014597-66vd2mdu 1314 26 solution solution NN cord-014597-66vd2mdu 1314 27 of of IN cord-014597-66vd2mdu 1314 28 a a DT cord-014597-66vd2mdu 1314 29 simple simple JJ cord-014597-66vd2mdu 1314 30 , , , cord-014597-66vd2mdu 1314 31 scalable scalable JJ cord-014597-66vd2mdu 1314 32 , , , cord-014597-66vd2mdu 1314 33 and and CC cord-014597-66vd2mdu 1314 34 fully fully RB cord-014597-66vd2mdu 1314 35 - - HYPH cord-014597-66vd2mdu 1314 36 disposable disposable JJ cord-014597-66vd2mdu 1314 37 vaccine vaccine NN cord-014597-66vd2mdu 1314 38 production production NN cord-014597-66vd2mdu 1314 39 platform platform NN cord-014597-66vd2mdu 1314 40 resulting result VBG cord-014597-66vd2mdu 1314 41 in in IN cord-014597-66vd2mdu 1314 42 long long JJ cord-014597-66vd2mdu 1314 43 - - HYPH cord-014597-66vd2mdu 1314 44 term term NN cord-014597-66vd2mdu 1314 45 cost cost NN cord-014597-66vd2mdu 1314 46 - - HYPH cord-014597-66vd2mdu 1314 47 effectiveness effectiveness NN cord-014597-66vd2mdu 1314 48 , , , cord-014597-66vd2mdu 1314 49 flexibility flexibility NN cord-014597-66vd2mdu 1314 50 and and CC cord-014597-66vd2mdu 1314 51 sustainability sustainability NN cord-014597-66vd2mdu 1314 52 : : : cord-014597-66vd2mdu 1314 53 -All -All `` cord-014597-66vd2mdu 1314 54 upstream upstream RB cord-014597-66vd2mdu 1314 55 , , , cord-014597-66vd2mdu 1314 56 downstream downstream JJ cord-014597-66vd2mdu 1314 57 and and CC cord-014597-66vd2mdu 1314 58 inactivation inactivation NN cord-014597-66vd2mdu 1314 59 steps step NNS cord-014597-66vd2mdu 1314 60 take take VBP cord-014597-66vd2mdu 1314 61 place place NN cord-014597-66vd2mdu 1314 62 within within IN cord-014597-66vd2mdu 1314 63 a a DT cord-014597-66vd2mdu 1314 64 closed closed JJ cord-014597-66vd2mdu 1314 65 system system NN cord-014597-66vd2mdu 1314 66 with with IN cord-014597-66vd2mdu 1314 67 all all PDT cord-014597-66vd2mdu 1314 68 the the DT cord-014597-66vd2mdu 1314 69 equipment equipment NN cord-014597-66vd2mdu 1314 70 contained contain VBN cord-014597-66vd2mdu 1314 71 in in IN cord-014597-66vd2mdu 1314 72 a a DT cord-014597-66vd2mdu 1314 73 low low JJ cord-014597-66vd2mdu 1314 74 footprint footprint NN cord-014597-66vd2mdu 1314 75 isolatorcreating isolatorcreate VBG cord-014597-66vd2mdu 1314 76 a a DT cord-014597-66vd2mdu 1314 77 confined confine VBN cord-014597-66vd2mdu 1314 78 area area NN cord-014597-66vd2mdu 1314 79 for for IN cord-014597-66vd2mdu 1314 80 polio polio NN cord-014597-66vd2mdu 1314 81 virus virus NN cord-014597-66vd2mdu 1314 82 handling handle VBG cord-014597-66vd2mdu 1314 83 that that WDT cord-014597-66vd2mdu 1314 84 facilitates facilitate VBZ cord-014597-66vd2mdu 1314 85 the the DT cord-014597-66vd2mdu 1314 86 deployment deployment NN cord-014597-66vd2mdu 1314 87 of of IN cord-014597-66vd2mdu 1314 88 micro micro NNS cord-014597-66vd2mdu 1314 89 - - NNS cord-014597-66vd2mdu 1314 90 facilities facility NNS cord-014597-66vd2mdu 1314 91 . . . cord-014597-66vd2mdu 1315 1 -This -this NN cord-014597-66vd2mdu 1315 2 leads lead VBZ cord-014597-66vd2mdu 1315 3 to to IN cord-014597-66vd2mdu 1315 4 a a DT cord-014597-66vd2mdu 1315 5 dramatic dramatic JJ cord-014597-66vd2mdu 1315 6 reduction reduction NN cord-014597-66vd2mdu 1315 7 in in IN cord-014597-66vd2mdu 1315 8 capital capital NN cord-014597-66vd2mdu 1315 9 investment investment NN cord-014597-66vd2mdu 1315 10 , , , cord-014597-66vd2mdu 1315 11 time time NN cord-014597-66vd2mdu 1315 12 required require VBN cord-014597-66vd2mdu 1315 13 for for IN cord-014597-66vd2mdu 1315 14 development development NN cord-014597-66vd2mdu 1315 15 and and CC cord-014597-66vd2mdu 1315 16 increases increase NNS cord-014597-66vd2mdu 1315 17 production production NN cord-014597-66vd2mdu 1315 18 capacity capacity NN cord-014597-66vd2mdu 1315 19 . . . cord-014597-66vd2mdu 1316 1 -In -In : cord-014597-66vd2mdu 1316 2 conclusion conclusion NN cord-014597-66vd2mdu 1316 3 , , , cord-014597-66vd2mdu 1316 4 this this DT cord-014597-66vd2mdu 1316 5 is be VBZ cord-014597-66vd2mdu 1316 6 a a DT cord-014597-66vd2mdu 1316 7 simple simple JJ cord-014597-66vd2mdu 1316 8 and and CC cord-014597-66vd2mdu 1316 9 elegant elegant JJ cord-014597-66vd2mdu 1316 10 solution solution NN cord-014597-66vd2mdu 1316 11 for for IN cord-014597-66vd2mdu 1316 12 the the DT cord-014597-66vd2mdu 1316 13 industrial industrial JJ cord-014597-66vd2mdu 1316 14 production production NN cord-014597-66vd2mdu 1316 15 of of IN cord-014597-66vd2mdu 1316 16 human human JJ cord-014597-66vd2mdu 1316 17 vaccines vaccine NNS cord-014597-66vd2mdu 1316 18 at at IN cord-014597-66vd2mdu 1316 19 a a DT cord-014597-66vd2mdu 1316 20 low low JJ cord-014597-66vd2mdu 1316 21 cost cost NN cord-014597-66vd2mdu 1316 22 in in IN cord-014597-66vd2mdu 1316 23 micro micro JJ cord-014597-66vd2mdu 1316 24 - - NNS cord-014597-66vd2mdu 1316 25 facilities facility NNS cord-014597-66vd2mdu 1316 26 , , , cord-014597-66vd2mdu 1316 27 making make VBG cord-014597-66vd2mdu 1316 28 polio polio NN cord-014597-66vd2mdu 1316 29 vaccines vaccine NNS cord-014597-66vd2mdu 1316 30 available available JJ cord-014597-66vd2mdu 1316 31 to to IN cord-014597-66vd2mdu 1316 32 all all DT cord-014597-66vd2mdu 1316 33 . . . cord-014597-66vd2mdu 1317 1 Comparison comparison NN cord-014597-66vd2mdu 1317 2 of of IN cord-014597-66vd2mdu 1317 3 media medium NNS cord-014597-66vd2mdu 1317 4 formulations formulation NNS cord-014597-66vd2mdu 1317 5 for for IN cord-014597-66vd2mdu 1317 6 the the DT cord-014597-66vd2mdu 1317 7 vaccine vaccine NN cord-014597-66vd2mdu 1317 8 production production NN cord-014597-66vd2mdu 1317 9 in in IN cord-014597-66vd2mdu 1317 10 1 1 CD cord-014597-66vd2mdu 1317 11 L l NN cord-014597-66vd2mdu 1317 12 stirred stir VBN cord-014597-66vd2mdu 1317 13 tank tank NN cord-014597-66vd2mdu 1317 14 bioreactors bioreactor NNS cord-014597-66vd2mdu 1317 15 operated operate VBN cord-014597-66vd2mdu 1317 16 in in IN cord-014597-66vd2mdu 1317 17 continuous continuous JJ cord-014597-66vd2mdu 1317 18 mode mode NN cord-014597-66vd2mdu 1317 19 . . . cord-014597-66vd2mdu 1318 1 Both both DT cord-014597-66vd2mdu 1318 2 cultures culture NNS cord-014597-66vd2mdu 1318 3 were be VBD cord-014597-66vd2mdu 1318 4 performed perform VBN cord-014597-66vd2mdu 1318 5 in in IN cord-014597-66vd2mdu 1318 6 parallel parallel NN cord-014597-66vd2mdu 1318 7 using use VBG cord-014597-66vd2mdu 1318 8 the the DT cord-014597-66vd2mdu 1318 9 corresponding corresponding JJ cord-014597-66vd2mdu 1318 10 medium medium NN cord-014597-66vd2mdu 1318 11 for for IN cord-014597-66vd2mdu 1318 12 the the DT cord-014597-66vd2mdu 1318 13 perfusion perfusion NN cord-014597-66vd2mdu 1318 14 . . . cord-014597-66vd2mdu 1319 1 a a DT cord-014597-66vd2mdu 1319 2 Feeding feeding NN cord-014597-66vd2mdu 1319 3 was be VBD cord-014597-66vd2mdu 1319 4 performed perform VBN cord-014597-66vd2mdu 1319 5 with with IN cord-014597-66vd2mdu 1319 6 the the DT cord-014597-66vd2mdu 1319 7 commercial commercial JJ cord-014597-66vd2mdu 1319 8 SFM SFM NNP cord-014597-66vd2mdu 1319 9 . . . cord-014597-66vd2mdu 1320 1 b b LS cord-014597-66vd2mdu 1320 2 The the DT cord-014597-66vd2mdu 1320 3 first first JJ cord-014597-66vd2mdu 1320 4 two two CD cord-014597-66vd2mdu 1320 5 days day NNS cord-014597-66vd2mdu 1320 6 of of IN cord-014597-66vd2mdu 1320 7 perfusion perfusion NN cord-014597-66vd2mdu 1320 8 feeding feeding NN cord-014597-66vd2mdu 1320 9 was be VBD cord-014597-66vd2mdu 1320 10 performed perform VBN cord-014597-66vd2mdu 1320 11 with with IN cord-014597-66vd2mdu 1320 12 SFM SFM NNP cord-014597-66vd2mdu 1320 13 until until IN cord-014597-66vd2mdu 1320 14 the the DT cord-014597-66vd2mdu 1320 15 cell cell NN cord-014597-66vd2mdu 1320 16 density density NN cord-014597-66vd2mdu 1320 17 reach reach VBP cord-014597-66vd2mdu 1320 18 10 10 CD cord-014597-66vd2mdu 1320 19 7 7 CD cord-014597-66vd2mdu 1320 20 cells.ml cells.ml CD cord-014597-66vd2mdu 1320 21 -1 -1 CD cord-014597-66vd2mdu 1321 1 and and CC cord-014597-66vd2mdu 1321 2 , , , cord-014597-66vd2mdu 1321 3 after after IN cord-014597-66vd2mdu 1321 4 that that DT cord-014597-66vd2mdu 1321 5 , , , cord-014597-66vd2mdu 1321 6 the the DT cord-014597-66vd2mdu 1321 7 bioreactor bioreactor NN cord-014597-66vd2mdu 1321 8 was be VBD cord-014597-66vd2mdu 1321 9 fed feed VBN cord-014597-66vd2mdu 1321 10 using use VBG cord-014597-66vd2mdu 1321 11 the the DT cord-014597-66vd2mdu 1321 12 RVPM RVPM NNP cord-014597-66vd2mdu 1321 13 formulation formulation NN cord-014597-66vd2mdu 1321 14 . . . cord-014597-66vd2mdu 1322 1 ( ( -LRB- cord-014597-66vd2mdu 1322 2 ↓ ↓ NFP cord-014597-66vd2mdu 1322 3 ) ) -RRB- cord-014597-66vd2mdu 1322 4 On on IN cord-014597-66vd2mdu 1322 5 day day NN cord-014597-66vd2mdu 1322 6 number number NN cord-014597-66vd2mdu 1322 7 10 10 CD cord-014597-66vd2mdu 1322 8 , , , cord-014597-66vd2mdu 1322 9 20 20 CD cord-014597-66vd2mdu 1322 10 % % NN cord-014597-66vd2mdu 1322 11 of of IN cord-014597-66vd2mdu 1322 12 the the DT cord-014597-66vd2mdu 1322 13 reactor reactor NN cord-014597-66vd2mdu 1322 14 volume volume NN cord-014597-66vd2mdu 1322 15 was be VBD cord-014597-66vd2mdu 1322 16 punctually punctually RB cord-014597-66vd2mdu 1322 17 bled bleed VBN cord-014597-66vd2mdu 1322 18 maintaining maintain VBG cord-014597-66vd2mdu 1322 19 the the DT cord-014597-66vd2mdu 1322 20 working work VBG cord-014597-66vd2mdu 1322 21 volume volume NN cord-014597-66vd2mdu 1322 22 Background Background NNP cord-014597-66vd2mdu 1322 23 Vectored vectore VBD cord-014597-66vd2mdu 1322 24 vaccines vaccine NNS cord-014597-66vd2mdu 1322 25 based base VBN cord-014597-66vd2mdu 1322 26 on on IN cord-014597-66vd2mdu 1322 27 modified modify VBN cord-014597-66vd2mdu 1322 28 vaccinia vaccinia NN cord-014597-66vd2mdu 1322 29 virus virus NN cord-014597-66vd2mdu 1323 1 Ankara Ankara NNP cord-014597-66vd2mdu 1323 2 ( ( -LRB- cord-014597-66vd2mdu 1323 3 MVA MVA NNP cord-014597-66vd2mdu 1323 4 ) ) -RRB- cord-014597-66vd2mdu 1323 5 are be VBP cord-014597-66vd2mdu 1323 6 reported report VBN cord-014597-66vd2mdu 1323 7 to to TO cord-014597-66vd2mdu 1323 8 stably stably RB cord-014597-66vd2mdu 1323 9 maintain maintain VB cord-014597-66vd2mdu 1323 10 large large JJ cord-014597-66vd2mdu 1323 11 transgenes transgene NNS cord-014597-66vd2mdu 1323 12 , , , cord-014597-66vd2mdu 1323 13 and and CC cord-014597-66vd2mdu 1323 14 to to TO cord-014597-66vd2mdu 1323 15 be be VB cord-014597-66vd2mdu 1323 16 safe safe JJ cord-014597-66vd2mdu 1323 17 , , , cord-014597-66vd2mdu 1323 18 immunogenic immunogenic JJ cord-014597-66vd2mdu 1323 19 and and CC cord-014597-66vd2mdu 1323 20 tolerant tolerant JJ cord-014597-66vd2mdu 1323 21 to to TO cord-014597-66vd2mdu 1323 22 pre pre VB cord-014597-66vd2mdu 1323 23 - - JJ cord-014597-66vd2mdu 1323 24 existing existing JJ cord-014597-66vd2mdu 1323 25 immunity immunity NN cord-014597-66vd2mdu 1323 26 . . . cord-014597-66vd2mdu 1324 1 MVA MVA NNP cord-014597-66vd2mdu 1324 2 is be VBZ cord-014597-66vd2mdu 1324 3 usually usually RB cord-014597-66vd2mdu 1324 4 produced produce VBN cord-014597-66vd2mdu 1324 5 on on IN cord-014597-66vd2mdu 1324 6 primary primary JJ cord-014597-66vd2mdu 1324 7 chicken chicken NN cord-014597-66vd2mdu 1324 8 embryo embryo NN cord-014597-66vd2mdu 1324 9 fibroblasts fibroblast NNS cord-014597-66vd2mdu 1324 10 but but CC cord-014597-66vd2mdu 1324 11 continuous continuous JJ cord-014597-66vd2mdu 1324 12 cell cell NN cord-014597-66vd2mdu 1324 13 lines line NNS cord-014597-66vd2mdu 1324 14 are be VBP cord-014597-66vd2mdu 1324 15 being be VBG cord-014597-66vd2mdu 1324 16 investigated investigate VBN cord-014597-66vd2mdu 1324 17 as as IN cord-014597-66vd2mdu 1324 18 more more RBR cord-014597-66vd2mdu 1324 19 versatile versatile JJ cord-014597-66vd2mdu 1324 20 substrates substrate NNS cord-014597-66vd2mdu 1324 21 . . . cord-014597-66vd2mdu 1325 1 We -PRON- PRP cord-014597-66vd2mdu 1325 2 have have VBP cord-014597-66vd2mdu 1325 3 previously previously RB cord-014597-66vd2mdu 1325 4 reported report VBN cord-014597-66vd2mdu 1325 5 development development NN cord-014597-66vd2mdu 1325 6 of of IN cord-014597-66vd2mdu 1325 7 a a DT cord-014597-66vd2mdu 1325 8 continuous continuous JJ cord-014597-66vd2mdu 1325 9 suspension suspension NN cord-014597-66vd2mdu 1325 10 cell cell NN cord-014597-66vd2mdu 1325 11 line line NN cord-014597-66vd2mdu 1325 12 ( ( -LRB- cord-014597-66vd2mdu 1325 13 CR.pIX CR.pIX NNP cord-014597-66vd2mdu 1325 14 ) ) -RRB- cord-014597-66vd2mdu 1325 15 derived derive VBN cord-014597-66vd2mdu 1325 16 from from IN cord-014597-66vd2mdu 1325 17 the the DT cord-014597-66vd2mdu 1325 18 muscovy muscovy NNP cord-014597-66vd2mdu 1325 19 duck duck NN cord-014597-66vd2mdu 1325 20 and and CC cord-014597-66vd2mdu 1325 21 efficient efficient JJ cord-014597-66vd2mdu 1325 22 production production NN cord-014597-66vd2mdu 1325 23 process process NN cord-014597-66vd2mdu 1325 24 for for IN cord-014597-66vd2mdu 1325 25 MVA MVA NNP cord-014597-66vd2mdu 1325 26 in in IN cord-014597-66vd2mdu 1325 27 chemically chemically RB cord-014597-66vd2mdu 1325 28 defined define VBN cord-014597-66vd2mdu 1325 29 media medium NNS cord-014597-66vd2mdu 1325 30 [ [ -LRB- cord-014597-66vd2mdu 1325 31 1 1 CD cord-014597-66vd2mdu 1325 32 , , , cord-014597-66vd2mdu 1325 33 2 2 CD cord-014597-66vd2mdu 1325 34 ] ] -RRB- cord-014597-66vd2mdu 1325 35 . . . cord-014597-66vd2mdu 1326 1 This this DT cord-014597-66vd2mdu 1326 2 process process NN cord-014597-66vd2mdu 1326 3 allowed allow VBD cord-014597-66vd2mdu 1326 4 isolation isolation NN cord-014597-66vd2mdu 1326 5 of of IN cord-014597-66vd2mdu 1326 6 an an DT cord-014597-66vd2mdu 1326 7 hitherto hitherto RB cord-014597-66vd2mdu 1326 8 undescribed undescribed JJ cord-014597-66vd2mdu 1326 9 genotype genotype NN cord-014597-66vd2mdu 1326 10 ( ( -LRB- cord-014597-66vd2mdu 1326 11 MVA MVA NNP cord-014597-66vd2mdu 1326 12 - - HYPH cord-014597-66vd2mdu 1326 13 CR19 CR19 NNP cord-014597-66vd2mdu 1326 14 ) ) -RRB- cord-014597-66vd2mdu 1326 15 that that WDT cord-014597-66vd2mdu 1326 16 induced induce VBD cord-014597-66vd2mdu 1326 17 fewer few JJR cord-014597-66vd2mdu 1326 18 syncytia syncytia NN cord-014597-66vd2mdu 1326 19 in in IN cord-014597-66vd2mdu 1326 20 adherent adherent JJ cord-014597-66vd2mdu 1326 21 cultures culture NNS cord-014597-66vd2mdu 1326 22 and and CC cord-014597-66vd2mdu 1326 23 replicated replicate VBD cord-014597-66vd2mdu 1326 24 to to IN cord-014597-66vd2mdu 1326 25 higher high JJR cord-014597-66vd2mdu 1326 26 infectious infectious JJ cord-014597-66vd2mdu 1326 27 titers titer NNS cord-014597-66vd2mdu 1326 28 in in IN cord-014597-66vd2mdu 1326 29 the the DT cord-014597-66vd2mdu 1326 30 extracellular extracellular JJ cord-014597-66vd2mdu 1326 31 volume volume NN cord-014597-66vd2mdu 1326 32 of of IN cord-014597-66vd2mdu 1326 33 suspension suspension NN cord-014597-66vd2mdu 1326 34 cultures culture NNS cord-014597-66vd2mdu 1326 35 [ [ -LRB- cord-014597-66vd2mdu 1326 36 3 3 CD cord-014597-66vd2mdu 1326 37 ] ] -RRB- cord-014597-66vd2mdu 1326 38 . . . cord-014597-66vd2mdu 1327 1 Replication replication NN cord-014597-66vd2mdu 1327 2 of of IN cord-014597-66vd2mdu 1327 3 MVA MVA NNP cord-014597-66vd2mdu 1327 4 - - HYPH cord-014597-66vd2mdu 1327 5 CR19 CR19 NNP cord-014597-66vd2mdu 1327 6 remained remain VBD cord-014597-66vd2mdu 1327 7 restricted restrict VBN cord-014597-66vd2mdu 1327 8 predominantely predominantely RB cord-014597-66vd2mdu 1327 9 to to IN cord-014597-66vd2mdu 1327 10 avian avian JJ cord-014597-66vd2mdu 1327 11 cells cell NNS cord-014597-66vd2mdu 1327 12 , , , cord-014597-66vd2mdu 1327 13 an an DT cord-014597-66vd2mdu 1327 14 important important JJ cord-014597-66vd2mdu 1327 15 property property NN cord-014597-66vd2mdu 1327 16 of of IN cord-014597-66vd2mdu 1327 17 MVA MVA NNP cord-014597-66vd2mdu 1327 18 vectors vector NNS cord-014597-66vd2mdu 1327 19 . . . cord-014597-66vd2mdu 1328 1 Homologous homologous JJ cord-014597-66vd2mdu 1328 2 recombination recombination NN cord-014597-66vd2mdu 1328 3 in in IN cord-014597-66vd2mdu 1328 4 CR.pIX CR.pIX NNP cord-014597-66vd2mdu 1328 5 cells cell NNS cord-014597-66vd2mdu 1328 6 was be VBD cord-014597-66vd2mdu 1328 7 used use VBN cord-014597-66vd2mdu 1328 8 to to TO cord-014597-66vd2mdu 1328 9 generate generate VB cord-014597-66vd2mdu 1328 10 viruses virus NNS cord-014597-66vd2mdu 1328 11 with with IN cord-014597-66vd2mdu 1328 12 various various JJ cord-014597-66vd2mdu 1328 13 expression expression NN cord-014597-66vd2mdu 1328 14 cassettes cassette NNS cord-014597-66vd2mdu 1328 15 in in IN cord-014597-66vd2mdu 1328 16 deletion deletion NN cord-014597-66vd2mdu 1328 17 site site NN cord-014597-66vd2mdu 1328 18 III iii CD cord-014597-66vd2mdu 1328 19 [ [ -LRB- cord-014597-66vd2mdu 1328 20 4 4 CD cord-014597-66vd2mdu 1328 21 ] ] -RRB- cord-014597-66vd2mdu 1328 22 and and CC cord-014597-66vd2mdu 1328 23 combinations combination NNS cord-014597-66vd2mdu 1328 24 of of IN cord-014597-66vd2mdu 1328 25 the the DT cord-014597-66vd2mdu 1328 26 differentiating differentiating JJ cord-014597-66vd2mdu 1328 27 point point NN cord-014597-66vd2mdu 1328 28 mutations mutation NNS cord-014597-66vd2mdu 1328 29 of of IN cord-014597-66vd2mdu 1328 30 MVA MVA NNP cord-014597-66vd2mdu 1328 31 - - HYPH cord-014597-66vd2mdu 1328 32 CR19 CR19 NNP cord-014597-66vd2mdu 1328 33 in in IN cord-014597-66vd2mdu 1328 34 a a DT cord-014597-66vd2mdu 1328 35 backbone backbone NN cord-014597-66vd2mdu 1328 36 of of IN cord-014597-66vd2mdu 1328 37 wildtype wildtype JJ cord-014597-66vd2mdu 1328 38 virus virus NN cord-014597-66vd2mdu 1328 39 . . . cord-014597-66vd2mdu 1329 1 All all DT cord-014597-66vd2mdu 1329 2 recombinant recombinant JJ cord-014597-66vd2mdu 1329 3 viruses virus NNS cord-014597-66vd2mdu 1329 4 were be VBD cord-014597-66vd2mdu 1329 5 plaquepurified plaquepurifie VBN cord-014597-66vd2mdu 1329 6 . . . cord-014597-66vd2mdu 1330 1 Successful successful JJ cord-014597-66vd2mdu 1330 2 introduction introduction NN cord-014597-66vd2mdu 1330 3 of of IN cord-014597-66vd2mdu 1330 4 the the DT cord-014597-66vd2mdu 1330 5 mutations mutation NNS cord-014597-66vd2mdu 1330 6 was be VBD cord-014597-66vd2mdu 1330 7 confirmed confirm VBN cord-014597-66vd2mdu 1330 8 by by IN cord-014597-66vd2mdu 1330 9 sequencing sequence VBG cord-014597-66vd2mdu 1330 10 and and CC cord-014597-66vd2mdu 1330 11 specifically specifically RB cord-014597-66vd2mdu 1330 12 designed design VBN cord-014597-66vd2mdu 1330 13 restriction restriction NN cord-014597-66vd2mdu 1330 14 fragment fragment NN cord-014597-66vd2mdu 1330 15 length length NN cord-014597-66vd2mdu 1330 16 polymorphisms polymorphism NNS cord-014597-66vd2mdu 1330 17 ( ( -LRB- cord-014597-66vd2mdu 1330 18 RFLPs rflp NNS cord-014597-66vd2mdu 1330 19 ) ) -RRB- cord-014597-66vd2mdu 1330 20 . . . cord-014597-66vd2mdu 1331 1 Viruses virus NNS cord-014597-66vd2mdu 1331 2 were be VBD cord-014597-66vd2mdu 1331 3 analyzed analyze VBN cord-014597-66vd2mdu 1331 4 by by IN cord-014597-66vd2mdu 1331 5 serial serial JJ cord-014597-66vd2mdu 1331 6 passaging passaging NN cord-014597-66vd2mdu 1331 7 , , , cord-014597-66vd2mdu 1331 8 diagnostic diagnostic JJ cord-014597-66vd2mdu 1331 9 PCRs pcr NNS cord-014597-66vd2mdu 1331 10 accross accross IN cord-014597-66vd2mdu 1331 11 deletion deletion NN cord-014597-66vd2mdu 1331 12 sites site NNS cord-014597-66vd2mdu 1331 13 [ [ -LRB- cord-014597-66vd2mdu 1331 14 4 4 CD cord-014597-66vd2mdu 1331 15 ] ] -RRB- cord-014597-66vd2mdu 1331 16 , , , cord-014597-66vd2mdu 1331 17 replication replication NN cord-014597-66vd2mdu 1331 18 kinetics kinetics NN cord-014597-66vd2mdu 1331 19 , , , cord-014597-66vd2mdu 1331 20 plaque plaque NN cord-014597-66vd2mdu 1331 21 phenotype phenotype NN cord-014597-66vd2mdu 1331 22 and and CC cord-014597-66vd2mdu 1331 23 electron electron NN cord-014597-66vd2mdu 1331 24 microscopy microscopy NN cord-014597-66vd2mdu 1331 25 . . . cord-014597-66vd2mdu 1332 1 The the DT cord-014597-66vd2mdu 1332 2 genome genome NN cord-014597-66vd2mdu 1332 3 was be VBD cord-014597-66vd2mdu 1332 4 further further RB cord-014597-66vd2mdu 1332 5 investigated investigate VBN cord-014597-66vd2mdu 1332 6 by by IN cord-014597-66vd2mdu 1332 7 anchored anchor VBN cord-014597-66vd2mdu 1332 8 PCR PCR NNP cord-014597-66vd2mdu 1332 9 and and CC cord-014597-66vd2mdu 1332 10 long long JJ cord-014597-66vd2mdu 1332 11 PCR PCR NNP cord-014597-66vd2mdu 1332 12 . . . cord-014597-66vd2mdu 1333 1 Efficiency efficiency NN cord-014597-66vd2mdu 1333 2 of of IN cord-014597-66vd2mdu 1333 3 spread spread NN cord-014597-66vd2mdu 1333 4 of of IN cord-014597-66vd2mdu 1333 5 recombinant recombinant JJ cord-014597-66vd2mdu 1333 6 viruses virus NNS cord-014597-66vd2mdu 1333 7 ( ( -LRB- cord-014597-66vd2mdu 1333 8 Fig Fig NNP cord-014597-66vd2mdu 1333 9 . . . cord-014597-66vd2mdu 1333 10 1a 1a CD cord-014597-66vd2mdu 1333 11 ) ) -RRB- cord-014597-66vd2mdu 1333 12 could could MD cord-014597-66vd2mdu 1333 13 be be VB cord-014597-66vd2mdu 1333 14 mapped map VBN cord-014597-66vd2mdu 1333 15 to to IN cord-014597-66vd2mdu 1333 16 a a DT cord-014597-66vd2mdu 1333 17 point point NN cord-014597-66vd2mdu 1333 18 mutation mutation NN cord-014597-66vd2mdu 1333 19 in in IN cord-014597-66vd2mdu 1333 20 one one CD cord-014597-66vd2mdu 1333 21 of of IN cord-014597-66vd2mdu 1333 22 the the DT cord-014597-66vd2mdu 1333 23 genes gene NNS cord-014597-66vd2mdu 1333 24 , , , cord-014597-66vd2mdu 1334 1 A34R. a34r. UH cord-014597-66vd2mdu 1335 1 However however RB cord-014597-66vd2mdu 1335 2 , , , cord-014597-66vd2mdu 1335 3 although although IN cord-014597-66vd2mdu 1335 4 MVA MVA NNP cord-014597-66vd2mdu 1335 5 - - HYPH cord-014597-66vd2mdu 1335 6 CR19 CR19 NNP cord-014597-66vd2mdu 1335 7 carries carry VBZ cord-014597-66vd2mdu 1335 8 mutations mutation NNS cord-014597-66vd2mdu 1335 9 in in IN cord-014597-66vd2mdu 1335 10 three three CD cord-014597-66vd2mdu 1335 11 structural structural JJ cord-014597-66vd2mdu 1335 12 proteins protein NNS cord-014597-66vd2mdu 1335 13 we -PRON- PRP cord-014597-66vd2mdu 1335 14 detected detect VBD cord-014597-66vd2mdu 1335 15 no no DT cord-014597-66vd2mdu 1335 16 obvious obvious JJ cord-014597-66vd2mdu 1335 17 differences difference NNS cord-014597-66vd2mdu 1335 18 to to IN cord-014597-66vd2mdu 1335 19 wildtype wildtype NN cord-014597-66vd2mdu 1335 20 by by IN cord-014597-66vd2mdu 1335 21 electron electron NN cord-014597-66vd2mdu 1335 22 microscopy microscopy NNS cord-014597-66vd2mdu 1335 23 ( ( -LRB- cord-014597-66vd2mdu 1335 24 Fig fig NN cord-014597-66vd2mdu 1335 25 . . . cord-014597-66vd2mdu 1335 26 1b 1b CD cord-014597-66vd2mdu 1335 27 ) ) -RRB- cord-014597-66vd2mdu 1335 28 . . . cord-014597-66vd2mdu 1336 1 The the DT cord-014597-66vd2mdu 1336 2 replacement replacement NN cord-014597-66vd2mdu 1336 3 of of IN cord-014597-66vd2mdu 1336 4 the the DT cord-014597-66vd2mdu 1336 5 left left JJ cord-014597-66vd2mdu 1336 6 viral viral JJ cord-014597-66vd2mdu 1336 7 telomere telomere NN cord-014597-66vd2mdu 1336 8 by by IN cord-014597-66vd2mdu 1336 9 the the DT cord-014597-66vd2mdu 1336 10 right right JJ cord-014597-66vd2mdu 1336 11 counterpart counterpart NN cord-014597-66vd2mdu 1336 12 was be VBD cord-014597-66vd2mdu 1336 13 the the DT cord-014597-66vd2mdu 1336 14 most most RBS cord-014597-66vd2mdu 1336 15 surprising surprising JJ cord-014597-66vd2mdu 1336 16 result result NN cord-014597-66vd2mdu 1336 17 of of IN cord-014597-66vd2mdu 1336 18 our -PRON- PRP$ cord-014597-66vd2mdu 1336 19 new new JJ cord-014597-66vd2mdu 1336 20 study study NN cord-014597-66vd2mdu 1336 21 ( ( -LRB- cord-014597-66vd2mdu 1336 22 Fig Fig NNP cord-014597-66vd2mdu 1336 23 . . . cord-014597-66vd2mdu 1336 24 1c 1c CD cord-014597-66vd2mdu 1336 25 ) ) -RRB- cord-014597-66vd2mdu 1336 26 . . . cord-014597-66vd2mdu 1337 1 This this DT cord-014597-66vd2mdu 1337 2 extensive extensive JJ cord-014597-66vd2mdu 1337 3 rearrangement rearrangement NN cord-014597-66vd2mdu 1337 4 affects affect VBZ cord-014597-66vd2mdu 1337 5 15 15 CD cord-014597-66vd2mdu 1337 6 % % NN cord-014597-66vd2mdu 1337 7 of of IN cord-014597-66vd2mdu 1337 8 the the DT cord-014597-66vd2mdu 1337 9 viral viral JJ cord-014597-66vd2mdu 1337 10 genome genome NN cord-014597-66vd2mdu 1337 11 and and CC cord-014597-66vd2mdu 1337 12 has have VBZ cord-014597-66vd2mdu 1337 13 also also RB cord-014597-66vd2mdu 1337 14 increased increase VBN cord-014597-66vd2mdu 1337 15 the the DT cord-014597-66vd2mdu 1337 16 area area NN cord-014597-66vd2mdu 1337 17 of of IN cord-014597-66vd2mdu 1337 18 complementarity complementarity NN cord-014597-66vd2mdu 1337 19 between between IN cord-014597-66vd2mdu 1337 20 the the DT cord-014597-66vd2mdu 1337 21 two two CD cord-014597-66vd2mdu 1337 22 telomeres telomere NNS cord-014597-66vd2mdu 1337 23 . . . cord-014597-66vd2mdu 1338 1 The the DT cord-014597-66vd2mdu 1338 2 recombination recombination NN cord-014597-66vd2mdu 1338 3 site site NN cord-014597-66vd2mdu 1338 4 was be VBD cord-014597-66vd2mdu 1338 5 precisely precisely RB cord-014597-66vd2mdu 1338 6 located locate VBN cord-014597-66vd2mdu 1338 7 and and CC cord-014597-66vd2mdu 1338 8 shown show VBN cord-014597-66vd2mdu 1338 9 via via IN cord-014597-66vd2mdu 1338 10 analysis analysis NN cord-014597-66vd2mdu 1338 11 of of IN cord-014597-66vd2mdu 1338 12 earlier early JJR cord-014597-66vd2mdu 1338 13 and and CC cord-014597-66vd2mdu 1338 14 subsequent subsequent JJ cord-014597-66vd2mdu 1338 15 passages passage NNS cord-014597-66vd2mdu 1338 16 to to TO cord-014597-66vd2mdu 1338 17 be be VB cord-014597-66vd2mdu 1338 18 a a DT cord-014597-66vd2mdu 1338 19 stable stable JJ cord-014597-66vd2mdu 1338 20 property property NN cord-014597-66vd2mdu 1338 21 of of IN cord-014597-66vd2mdu 1338 22 MVA MVA NNP cord-014597-66vd2mdu 1338 23 - - HYPH cord-014597-66vd2mdu 1338 24 CR19 CR19 NNP cord-014597-66vd2mdu 1338 25 . . . cord-014597-66vd2mdu 1339 1 Various various JJ cord-014597-66vd2mdu 1339 2 viruses virus NNS cord-014597-66vd2mdu 1339 3 , , , cord-014597-66vd2mdu 1339 4 including include VBG cord-014597-66vd2mdu 1339 5 those those DT cord-014597-66vd2mdu 1339 6 with with IN cord-014597-66vd2mdu 1339 7 larger large JJR cord-014597-66vd2mdu 1339 8 dual dual JJ cord-014597-66vd2mdu 1339 9 ( ( -LRB- cord-014597-66vd2mdu 1339 10 DsRed1 dsred1 JJ cord-014597-66vd2mdu 1339 11 and and CC cord-014597-66vd2mdu 1339 12 GFP GFP NNP cord-014597-66vd2mdu 1339 13 ) ) -RRB- cord-014597-66vd2mdu 1339 14 expression expression NN cord-014597-66vd2mdu 1339 15 cassettes cassette NNS cord-014597-66vd2mdu 1339 16 , , , cord-014597-66vd2mdu 1339 17 were be VBD cord-014597-66vd2mdu 1339 18 serially serially RB cord-014597-66vd2mdu 1339 19 passaged passage VBN cord-014597-66vd2mdu 1339 20 at at IN cord-014597-66vd2mdu 1339 21 least least JJS cord-014597-66vd2mdu 1339 22 20-fold 20-fold CD cord-014597-66vd2mdu 1339 23 . . . cord-014597-66vd2mdu 1340 1 Although although IN cord-014597-66vd2mdu 1340 2 the the DT cord-014597-66vd2mdu 1340 3 genotype genotype NN cord-014597-66vd2mdu 1340 4 of of IN cord-014597-66vd2mdu 1340 5 MVA MVA NNP cord-014597-66vd2mdu 1340 6 - - HYPH cord-014597-66vd2mdu 1340 7 CR19 CR19 NNP cord-014597-66vd2mdu 1340 8 is be VBZ cord-014597-66vd2mdu 1340 9 advantageous advantageous JJ cord-014597-66vd2mdu 1340 10 for for IN cord-014597-66vd2mdu 1340 11 replication replication NN cord-014597-66vd2mdu 1340 12 , , , cord-014597-66vd2mdu 1340 13 all all DT cord-014597-66vd2mdu 1340 14 genomic genomic JJ cord-014597-66vd2mdu 1340 15 and and CC cord-014597-66vd2mdu 1340 16 genetic genetic JJ cord-014597-66vd2mdu 1340 17 markers marker NNS cord-014597-66vd2mdu 1340 18 of of IN cord-014597-66vd2mdu 1340 19 wildtype wildtype NN cord-014597-66vd2mdu 1340 20 and and CC cord-014597-66vd2mdu 1340 21 MVA MVA NNP cord-014597-66vd2mdu 1340 22 - - HYPH cord-014597-66vd2mdu 1340 23 CR19 CR19 NNP cord-014597-66vd2mdu 1340 24 were be VBD cord-014597-66vd2mdu 1340 25 stably stably RB cord-014597-66vd2mdu 1340 26 maintained maintain VBN cord-014597-66vd2mdu 1340 27 in in IN cord-014597-66vd2mdu 1340 28 all all DT cord-014597-66vd2mdu 1340 29 passages passage NNS cord-014597-66vd2mdu 1340 30 of of IN cord-014597-66vd2mdu 1340 31 the the DT cord-014597-66vd2mdu 1340 32 recombinant recombinant JJ cord-014597-66vd2mdu 1340 33 viruses virus NNS cord-014597-66vd2mdu 1340 34 , , , cord-014597-66vd2mdu 1340 35 independent independent JJ cord-014597-66vd2mdu 1340 36 of of IN cord-014597-66vd2mdu 1340 37 wildtype wildtype NN cord-014597-66vd2mdu 1340 38 or or CC cord-014597-66vd2mdu 1340 39 MVA MVA NNP cord-014597-66vd2mdu 1340 40 - - HYPH cord-014597-66vd2mdu 1340 41 CR19 CR19 NNP cord-014597-66vd2mdu 1340 42 backbone backbone NN cord-014597-66vd2mdu 1340 43 . . . cord-014597-66vd2mdu 1341 1 We -PRON- PRP cord-014597-66vd2mdu 1341 2 confirmed confirm VBD cord-014597-66vd2mdu 1341 3 our -PRON- PRP$ cord-014597-66vd2mdu 1341 4 previous previous JJ cord-014597-66vd2mdu 1341 5 results result NNS cord-014597-66vd2mdu 1341 6 that that WDT cord-014597-66vd2mdu 1341 7 suggested suggest VBD cord-014597-66vd2mdu 1341 8 that that IN cord-014597-66vd2mdu 1341 9 MVA MVA NNP cord-014597-66vd2mdu 1341 10 - - HYPH cord-014597-66vd2mdu 1341 11 CR19 CR19 NNP cord-014597-66vd2mdu 1341 12 replicates replicate VBZ cord-014597-66vd2mdu 1341 13 efficiently efficiently RB cord-014597-66vd2mdu 1341 14 in in IN cord-014597-66vd2mdu 1341 15 single single JJ cord-014597-66vd2mdu 1341 16 - - HYPH cord-014597-66vd2mdu 1341 17 cell cell NN cord-014597-66vd2mdu 1341 18 suspensions suspension NNS cord-014597-66vd2mdu 1341 19 and and CC cord-014597-66vd2mdu 1341 20 were be VBD cord-014597-66vd2mdu 1341 21 able able JJ cord-014597-66vd2mdu 1341 22 to to TO cord-014597-66vd2mdu 1341 23 connect connect VB cord-014597-66vd2mdu 1341 24 this this DT cord-014597-66vd2mdu 1341 25 property property NN cord-014597-66vd2mdu 1341 26 with with IN cord-014597-66vd2mdu 1341 27 the the DT cord-014597-66vd2mdu 1341 28 D86Y D86Y NNP cord-014597-66vd2mdu 1341 29 mutation mutation NN cord-014597-66vd2mdu 1341 30 in in IN cord-014597-66vd2mdu 1341 31 A34 A34 NNP cord-014597-66vd2mdu 1341 32 , , , cord-014597-66vd2mdu 1341 33 a a DT cord-014597-66vd2mdu 1341 34 structural structural JJ cord-014597-66vd2mdu 1341 35 protein protein NN cord-014597-66vd2mdu 1341 36 on on IN cord-014597-66vd2mdu 1341 37 the the DT cord-014597-66vd2mdu 1341 38 surface surface NN cord-014597-66vd2mdu 1341 39 of of IN cord-014597-66vd2mdu 1341 40 the the DT cord-014597-66vd2mdu 1341 41 virions virion NNS cord-014597-66vd2mdu 1341 42 . . . cord-014597-66vd2mdu 1342 1 MVA MVA NNP cord-014597-66vd2mdu 1342 2 - - HYPH cord-014597-66vd2mdu 1342 3 CR19 CR19 NNP cord-014597-66vd2mdu 1342 4 was be VBD cord-014597-66vd2mdu 1342 5 also also RB cord-014597-66vd2mdu 1342 6 found find VBN cord-014597-66vd2mdu 1342 7 to to TO cord-014597-66vd2mdu 1342 8 differ differ VB cord-014597-66vd2mdu 1342 9 from from IN cord-014597-66vd2mdu 1342 10 wildtype wildtype NN cord-014597-66vd2mdu 1342 11 MVA MVA NNP cord-014597-66vd2mdu 1342 12 by by IN cord-014597-66vd2mdu 1342 13 a a DT cord-014597-66vd2mdu 1342 14 recombination recombination NN cord-014597-66vd2mdu 1342 15 between between IN cord-014597-66vd2mdu 1342 16 left left JJ cord-014597-66vd2mdu 1342 17 and and CC cord-014597-66vd2mdu 1342 18 right right JJ cord-014597-66vd2mdu 1342 19 viral viral JJ cord-014597-66vd2mdu 1342 20 telomere telomere NN cord-014597-66vd2mdu 1342 21 . . . cord-014597-66vd2mdu 1343 1 Due due IN cord-014597-66vd2mdu 1343 2 to to IN cord-014597-66vd2mdu 1343 3 this this DT cord-014597-66vd2mdu 1343 4 event event NN cord-014597-66vd2mdu 1343 5 , , , cord-014597-66vd2mdu 1343 6 several several JJ cord-014597-66vd2mdu 1343 7 genes gene NNS cord-014597-66vd2mdu 1343 8 encoded encode VBN cord-014597-66vd2mdu 1343 9 at at IN cord-014597-66vd2mdu 1343 10 the the DT cord-014597-66vd2mdu 1343 11 left left JJ cord-014597-66vd2mdu 1343 12 terminus terminus NN cord-014597-66vd2mdu 1343 13 have have VBP cord-014597-66vd2mdu 1343 14 been be VBN cord-014597-66vd2mdu 1343 15 deleted delete VBN cord-014597-66vd2mdu 1343 16 whereas whereas IN cord-014597-66vd2mdu 1343 17 the the DT cord-014597-66vd2mdu 1343 18 gene gene NN cord-014597-66vd2mdu 1343 19 dosis dosis NN cord-014597-66vd2mdu 1343 20 of of IN cord-014597-66vd2mdu 1343 21 those those DT cord-014597-66vd2mdu 1343 22 originally originally RB cord-014597-66vd2mdu 1343 23 encoded encode VBN cord-014597-66vd2mdu 1343 24 only only RB cord-014597-66vd2mdu 1343 25 at at IN cord-014597-66vd2mdu 1343 26 the the DT cord-014597-66vd2mdu 1343 27 right right JJ cord-014597-66vd2mdu 1343 28 terminus terminus NN cord-014597-66vd2mdu 1343 29 may may MD cord-014597-66vd2mdu 1343 30 have have VB cord-014597-66vd2mdu 1343 31 increased increase VBN cord-014597-66vd2mdu 1343 32 . . . cord-014597-66vd2mdu 1344 1 We -PRON- PRP cord-014597-66vd2mdu 1344 2 do do VBP cord-014597-66vd2mdu 1344 3 not not RB cord-014597-66vd2mdu 1344 4 currently currently RB cord-014597-66vd2mdu 1344 5 know know VB cord-014597-66vd2mdu 1344 6 how how WRB cord-014597-66vd2mdu 1344 7 much much JJ cord-014597-66vd2mdu 1344 8 the the DT cord-014597-66vd2mdu 1344 9 various various JJ cord-014597-66vd2mdu 1344 10 point point NN cord-014597-66vd2mdu 1344 11 mutations mutation NNS cord-014597-66vd2mdu 1344 12 and and CC cord-014597-66vd2mdu 1344 13 changes change NNS cord-014597-66vd2mdu 1344 14 in in IN cord-014597-66vd2mdu 1344 15 genomic genomic JJ cord-014597-66vd2mdu 1344 16 structure structure NN cord-014597-66vd2mdu 1344 17 combine combine VBP cord-014597-66vd2mdu 1344 18 to to TO cord-014597-66vd2mdu 1344 19 explain explain VB cord-014597-66vd2mdu 1344 20 the the DT cord-014597-66vd2mdu 1344 21 improved improved JJ cord-014597-66vd2mdu 1344 22 replication replication NN cord-014597-66vd2mdu 1344 23 of of IN cord-014597-66vd2mdu 1344 24 MVA MVA NNP cord-014597-66vd2mdu 1344 25 - - HYPH cord-014597-66vd2mdu 1344 26 CR19 CR19 NNP cord-014597-66vd2mdu 1344 27 . . . cord-014597-66vd2mdu 1345 1 As as IN cord-014597-66vd2mdu 1345 2 several several JJ cord-014597-66vd2mdu 1345 3 of of IN cord-014597-66vd2mdu 1345 4 the the DT cord-014597-66vd2mdu 1345 5 affected affect VBN cord-014597-66vd2mdu 1345 6 genes gene NNS cord-014597-66vd2mdu 1345 7 have have VBP cord-014597-66vd2mdu 1345 8 been be VBN cord-014597-66vd2mdu 1345 9 reported report VBN cord-014597-66vd2mdu 1345 10 in in IN cord-014597-66vd2mdu 1345 11 the the DT cord-014597-66vd2mdu 1345 12 literature literature NN cord-014597-66vd2mdu 1345 13 to to IN cord-014597-66vd2mdu 1345 14 impact impact VB cord-014597-66vd2mdu 1345 15 interaction interaction NN cord-014597-66vd2mdu 1345 16 of of IN cord-014597-66vd2mdu 1345 17 MVA MVA NNP cord-014597-66vd2mdu 1345 18 with with IN cord-014597-66vd2mdu 1345 19 the the DT cord-014597-66vd2mdu 1345 20 host host NN cord-014597-66vd2mdu 1345 21 we -PRON- PRP cord-014597-66vd2mdu 1345 22 would would MD cord-014597-66vd2mdu 1345 23 expect expect VB cord-014597-66vd2mdu 1345 24 that that IN cord-014597-66vd2mdu 1345 25 in in IN cord-014597-66vd2mdu 1345 26 vivo vivo NN cord-014597-66vd2mdu 1345 27 studies study NNS cord-014597-66vd2mdu 1345 28 may may MD cord-014597-66vd2mdu 1345 29 reveal reveal VB cord-014597-66vd2mdu 1345 30 additional additional JJ cord-014597-66vd2mdu 1345 31 novel novel JJ cord-014597-66vd2mdu 1345 32 properties property NNS cord-014597-66vd2mdu 1345 33 of of IN cord-014597-66vd2mdu 1345 34 MVA MVA NNP cord-014597-66vd2mdu 1345 35 - - HYPH cord-014597-66vd2mdu 1345 36 CR19 CR19 NNP cord-014597-66vd2mdu 1345 37 . . . cord-014597-66vd2mdu 1346 1 An an DT cord-014597-66vd2mdu 1346 2 extremely extremely RB cord-014597-66vd2mdu 1346 3 important important JJ cord-014597-66vd2mdu 1346 4 distinction distinction NN cord-014597-66vd2mdu 1346 5 between between IN cord-014597-66vd2mdu 1346 6 our -PRON- PRP$ cord-014597-66vd2mdu 1346 7 earlier early JJR cord-014597-66vd2mdu 1346 8 study study NN cord-014597-66vd2mdu 1346 9 [ [ -LRB- cord-014597-66vd2mdu 1346 10 3 3 CD cord-014597-66vd2mdu 1346 11 ] ] -RRB- cord-014597-66vd2mdu 1346 12 and and CC cord-014597-66vd2mdu 1346 13 this this DT cord-014597-66vd2mdu 1346 14 one one CD cord-014597-66vd2mdu 1346 15 concerns concern VBZ cord-014597-66vd2mdu 1346 16 the the DT cord-014597-66vd2mdu 1346 17 source source NN cord-014597-66vd2mdu 1346 18 of of IN cord-014597-66vd2mdu 1346 19 the the DT cord-014597-66vd2mdu 1346 20 viruses virus NNS cord-014597-66vd2mdu 1346 21 . . . cord-014597-66vd2mdu 1347 1 Here here RB cord-014597-66vd2mdu 1347 2 , , , cord-014597-66vd2mdu 1347 3 we -PRON- PRP cord-014597-66vd2mdu 1347 4 investigated investigate VBD cord-014597-66vd2mdu 1347 5 plaque plaque NN cord-014597-66vd2mdu 1347 6 - - HYPH cord-014597-66vd2mdu 1347 7 purified purify VBN cord-014597-66vd2mdu 1347 8 viruses virus NNS cord-014597-66vd2mdu 1347 9 and and CC cord-014597-66vd2mdu 1347 10 confirm confirm VB cord-014597-66vd2mdu 1347 11 the the DT cord-014597-66vd2mdu 1347 12 high high JJ cord-014597-66vd2mdu 1347 13 genetic genetic JJ cord-014597-66vd2mdu 1347 14 and and CC cord-014597-66vd2mdu 1347 15 genomic genomic JJ cord-014597-66vd2mdu 1347 16 stability stability NN cord-014597-66vd2mdu 1347 17 of of IN cord-014597-66vd2mdu 1347 18 MVA MVA NNP cord-014597-66vd2mdu 1347 19 . . . cord-014597-66vd2mdu 1348 1 Different different JJ cord-014597-66vd2mdu 1348 2 expression expression NN cord-014597-66vd2mdu 1348 3 cassettes cassette NNS cord-014597-66vd2mdu 1348 4 inserted insert VBN cord-014597-66vd2mdu 1348 5 into into IN cord-014597-66vd2mdu 1348 6 deletion deletion NN cord-014597-66vd2mdu 1348 7 site site NN cord-014597-66vd2mdu 1348 8 III iii CD cord-014597-66vd2mdu 1348 9 , , , cord-014597-66vd2mdu 1348 10 all all DT cord-014597-66vd2mdu 1348 11 diagnostic diagnostic JJ cord-014597-66vd2mdu 1348 12 RFLPs rflp NNS cord-014597-66vd2mdu 1348 13 and and CC cord-014597-66vd2mdu 1348 14 PCRs pcr NNS cord-014597-66vd2mdu 1348 15 over over IN cord-014597-66vd2mdu 1348 16 various various JJ cord-014597-66vd2mdu 1348 17 sites site NNS cord-014597-66vd2mdu 1348 18 of of IN cord-014597-66vd2mdu 1348 19 the the DT cord-014597-66vd2mdu 1348 20 genome genome NN cord-014597-66vd2mdu 1348 21 and and CC cord-014597-66vd2mdu 1348 22 within within IN cord-014597-66vd2mdu 1348 23 the the DT cord-014597-66vd2mdu 1348 24 viral viral JJ cord-014597-66vd2mdu 1348 25 telomeres telomere NNS cord-014597-66vd2mdu 1348 26 remained remain VBD cord-014597-66vd2mdu 1348 27 unchanged unchanged JJ cord-014597-66vd2mdu 1348 28 throughout throughout IN cord-014597-66vd2mdu 1348 29 at at RB cord-014597-66vd2mdu 1348 30 least least RBS cord-014597-66vd2mdu 1348 31 20 20 CD cord-014597-66vd2mdu 1348 32 serial serial JJ cord-014597-66vd2mdu 1348 33 passages passage NNS cord-014597-66vd2mdu 1348 34 -independent -independent JJ cord-014597-66vd2mdu 1348 35 of of IN cord-014597-66vd2mdu 1348 36 whether whether IN cord-014597-66vd2mdu 1348 37 recombinant recombinant JJ cord-014597-66vd2mdu 1348 38 viruses virus NNS cord-014597-66vd2mdu 1348 39 with with IN cord-014597-66vd2mdu 1348 40 wildtype wildtype NN cord-014597-66vd2mdu 1348 41 or or CC cord-014597-66vd2mdu 1348 42 CR19-derived cr19-derived CD cord-014597-66vd2mdu 1348 43 backbones backbone NNS cord-014597-66vd2mdu 1348 44 were be VBD cord-014597-66vd2mdu 1348 45 characterized characterize VBN cord-014597-66vd2mdu 1348 46 . . . cord-014597-66vd2mdu 1349 1 Fig Fig NNP cord-014597-66vd2mdu 1349 2 . . . cord-014597-66vd2mdu 1349 3 1 1 CD cord-014597-66vd2mdu 1349 4 ( ( -LRB- cord-014597-66vd2mdu 1349 5 abstract abstract JJ cord-014597-66vd2mdu 1349 6 P-225 p-225 JJ cord-014597-66vd2mdu 1349 7 ) ) -RRB- cord-014597-66vd2mdu 1349 8 . . . cord-014597-66vd2mdu 1350 1 a a DT cord-014597-66vd2mdu 1350 2 One one CD cord-014597-66vd2mdu 1350 3 hallmark hallmark NN cord-014597-66vd2mdu 1350 4 of of IN cord-014597-66vd2mdu 1350 5 MVA MVA NNP cord-014597-66vd2mdu 1350 6 - - HYPH cord-014597-66vd2mdu 1350 7 CR19 CR19 NNP cord-014597-66vd2mdu 1350 8 is be VBZ cord-014597-66vd2mdu 1350 9 a a DT cord-014597-66vd2mdu 1350 10 significantly significantly RB cord-014597-66vd2mdu 1350 11 reduced reduce VBN cord-014597-66vd2mdu 1350 12 tendency tendency NN cord-014597-66vd2mdu 1350 13 to to TO cord-014597-66vd2mdu 1350 14 induce induce VB cord-014597-66vd2mdu 1350 15 syncytia syncytia NN cord-014597-66vd2mdu 1350 16 and and CC cord-014597-66vd2mdu 1350 17 an an DT cord-014597-66vd2mdu 1350 18 increased increase VBN cord-014597-66vd2mdu 1350 19 dispersion dispersion NN cord-014597-66vd2mdu 1350 20 of of IN cord-014597-66vd2mdu 1350 21 plaques plaque NNS cord-014597-66vd2mdu 1350 22 in in IN cord-014597-66vd2mdu 1350 23 CR.pIX CR.pIX NNP cord-014597-66vd2mdu 1350 24 cell cell NN cord-014597-66vd2mdu 1350 25 monolayers monolayer NNS cord-014597-66vd2mdu 1350 26 . . . cord-014597-66vd2mdu 1351 1 This this DT cord-014597-66vd2mdu 1351 2 property property NN cord-014597-66vd2mdu 1351 3 appears appear VBZ cord-014597-66vd2mdu 1351 4 to to TO cord-014597-66vd2mdu 1351 5 be be VB cord-014597-66vd2mdu 1351 6 supported support VBN cord-014597-66vd2mdu 1351 7 by by IN cord-014597-66vd2mdu 1351 8 the the DT cord-014597-66vd2mdu 1351 9 mutation mutation NN cord-014597-66vd2mdu 1351 10 in in IN cord-014597-66vd2mdu 1351 11 A34R. a34r. NN cord-014597-66vd2mdu 1351 12 b b NN cord-014597-66vd2mdu 1351 13 Electron electron NN cord-014597-66vd2mdu 1351 14 microscopy microscopy NN cord-014597-66vd2mdu 1351 15 reveals reveal VBZ cord-014597-66vd2mdu 1351 16 no no DT cord-014597-66vd2mdu 1351 17 obvious obvious JJ cord-014597-66vd2mdu 1351 18 differences difference NNS cord-014597-66vd2mdu 1351 19 between between IN cord-014597-66vd2mdu 1351 20 novel novel NN cord-014597-66vd2mdu 1351 21 genotype genotype NN cord-014597-66vd2mdu 1351 22 and and CC cord-014597-66vd2mdu 1351 23 wildtype wildtype NN cord-014597-66vd2mdu 1351 24 . . . cord-014597-66vd2mdu 1352 1 Background Background NNP cord-014597-66vd2mdu 1352 2 Transient transient JJ cord-014597-66vd2mdu 1352 3 gene gene NN cord-014597-66vd2mdu 1352 4 expression expression NN cord-014597-66vd2mdu 1352 5 systems system NNS cord-014597-66vd2mdu 1352 6 using use VBG cord-014597-66vd2mdu 1352 7 polyethylenimine polyethylenimine NNP cord-014597-66vd2mdu 1352 8 ( ( -LRB- cord-014597-66vd2mdu 1352 9 PEI PEI NNP cord-014597-66vd2mdu 1352 10 ) ) -RRB- cord-014597-66vd2mdu 1352 11 are be VBP cord-014597-66vd2mdu 1352 12 considered consider VBN cord-014597-66vd2mdu 1352 13 to to TO cord-014597-66vd2mdu 1352 14 be be VB cord-014597-66vd2mdu 1352 15 fast fast RB cord-014597-66vd2mdu 1352 16 , , , cord-014597-66vd2mdu 1352 17 flexible flexible JJ cord-014597-66vd2mdu 1352 18 and and CC cord-014597-66vd2mdu 1352 19 cost cost NN cord-014597-66vd2mdu 1352 20 - - HYPH cord-014597-66vd2mdu 1352 21 efficient efficient JJ cord-014597-66vd2mdu 1352 22 for for IN cord-014597-66vd2mdu 1352 23 recombinant recombinant JJ cord-014597-66vd2mdu 1352 24 protein protein NN cord-014597-66vd2mdu 1352 25 production production NN cord-014597-66vd2mdu 1352 26 [ [ -LRB- cord-014597-66vd2mdu 1352 27 1 1 CD cord-014597-66vd2mdu 1352 28 ] ] -RRB- cord-014597-66vd2mdu 1352 29 . . . cord-014597-66vd2mdu 1353 1 Transfection transfection NN cord-014597-66vd2mdu 1353 2 efficiency efficiency NN cord-014597-66vd2mdu 1353 3 depends depend VBZ cord-014597-66vd2mdu 1353 4 on on IN cord-014597-66vd2mdu 1353 5 different different JJ cord-014597-66vd2mdu 1353 6 factors factor NNS cord-014597-66vd2mdu 1353 7 ; ; : cord-014597-66vd2mdu 1353 8 one one CD cord-014597-66vd2mdu 1353 9 of of IN cord-014597-66vd2mdu 1353 10 them -PRON- PRP cord-014597-66vd2mdu 1353 11 is be VBZ cord-014597-66vd2mdu 1353 12 the the DT cord-014597-66vd2mdu 1353 13 type type NN cord-014597-66vd2mdu 1353 14 of of IN cord-014597-66vd2mdu 1353 15 media medium NNS cord-014597-66vd2mdu 1353 16 . . . cord-014597-66vd2mdu 1354 1 Production production NN cord-014597-66vd2mdu 1354 2 media medium NNS cord-014597-66vd2mdu 1354 3 support support NN cord-014597-66vd2mdu 1354 4 cell cell NN cord-014597-66vd2mdu 1354 5 growth growth NN cord-014597-66vd2mdu 1354 6 and and CC cord-014597-66vd2mdu 1354 7 protein protein NN cord-014597-66vd2mdu 1354 8 production production NN cord-014597-66vd2mdu 1354 9 but but CC cord-014597-66vd2mdu 1354 10 not not RB cord-014597-66vd2mdu 1354 11 high high JJ cord-014597-66vd2mdu 1354 12 transfection transfection NN cord-014597-66vd2mdu 1354 13 efficiency efficiency NN cord-014597-66vd2mdu 1354 14 ( ( -LRB- cord-014597-66vd2mdu 1354 15 TE TE NNP cord-014597-66vd2mdu 1354 16 ) ) -RRB- cord-014597-66vd2mdu 1354 17 mediated mediate VBN cord-014597-66vd2mdu 1354 18 by by IN cord-014597-66vd2mdu 1354 19 PEI PEI NNP cord-014597-66vd2mdu 1354 20 [ [ -LRB- cord-014597-66vd2mdu 1354 21 2 2 CD cord-014597-66vd2mdu 1354 22 ] ] -RRB- cord-014597-66vd2mdu 1354 23 . . . cord-014597-66vd2mdu 1355 1 Therefore therefore RB cord-014597-66vd2mdu 1355 2 , , , cord-014597-66vd2mdu 1355 3 media medium NNS cord-014597-66vd2mdu 1355 4 were be VBD cord-014597-66vd2mdu 1355 5 selected select VBN cord-014597-66vd2mdu 1355 6 for for IN cord-014597-66vd2mdu 1355 7 transfection transfection NN cord-014597-66vd2mdu 1355 8 followed follow VBN cord-014597-66vd2mdu 1355 9 by by IN cord-014597-66vd2mdu 1355 10 feeding feed VBG cord-014597-66vd2mdu 1355 11 of of IN cord-014597-66vd2mdu 1355 12 production production NN cord-014597-66vd2mdu 1355 13 media medium NNS cord-014597-66vd2mdu 1355 14 [ [ -LRB- cord-014597-66vd2mdu 1355 15 3 3 CD cord-014597-66vd2mdu 1355 16 ] ] -RRB- cord-014597-66vd2mdu 1355 17 to to TO cord-014597-66vd2mdu 1355 18 improve improve VB cord-014597-66vd2mdu 1355 19 TE TE NNP cord-014597-66vd2mdu 1355 20 and and CC cord-014597-66vd2mdu 1355 21 protein protein NN cord-014597-66vd2mdu 1355 22 production production NN cord-014597-66vd2mdu 1355 23 . . . cord-014597-66vd2mdu 1356 1 Two two CD cord-014597-66vd2mdu 1356 2 different different JJ cord-014597-66vd2mdu 1356 3 transfection transfection NN cord-014597-66vd2mdu 1356 4 strategies strategy NNS cord-014597-66vd2mdu 1356 5 are be VBP cord-014597-66vd2mdu 1356 6 compared compare VBN cord-014597-66vd2mdu 1356 7 : : : cord-014597-66vd2mdu 1356 8 conventional conventional JJ cord-014597-66vd2mdu 1356 9 transfection transfection NN cord-014597-66vd2mdu 1356 10 by by IN cord-014597-66vd2mdu 1356 11 preparing prepare VBG cord-014597-66vd2mdu 1356 12 polyplex polyplex NN cord-014597-66vd2mdu 1356 13 of of IN cord-014597-66vd2mdu 1356 14 a a DT cord-014597-66vd2mdu 1356 15 plasmid plasmid NN cord-014597-66vd2mdu 1356 16 ( ( -LRB- cord-014597-66vd2mdu 1356 17 pDNA pdna RB cord-014597-66vd2mdu 1356 18 ) ) -RRB- cord-014597-66vd2mdu 1356 19 and and CC cord-014597-66vd2mdu 1356 20 PEI PEI NNP cord-014597-66vd2mdu 1356 21 interaction interaction NN cord-014597-66vd2mdu 1356 22 before before IN cord-014597-66vd2mdu 1356 23 transfection transfection NN cord-014597-66vd2mdu 1356 24 and and CC cord-014597-66vd2mdu 1356 25 insitu insitu JJ cord-014597-66vd2mdu 1356 26 transfection transfection NN cord-014597-66vd2mdu 1356 27 by by IN cord-014597-66vd2mdu 1356 28 direct direct JJ cord-014597-66vd2mdu 1356 29 addition addition NN cord-014597-66vd2mdu 1356 30 both both DT cord-014597-66vd2mdu 1356 31 of of IN cord-014597-66vd2mdu 1356 32 them -PRON- PRP cord-014597-66vd2mdu 1356 33 to to IN cord-014597-66vd2mdu 1356 34 the the DT cord-014597-66vd2mdu 1356 35 cell cell NN cord-014597-66vd2mdu 1356 36 suspension suspension NN cord-014597-66vd2mdu 1356 37 and and CC cord-014597-66vd2mdu 1356 38 the the DT cord-014597-66vd2mdu 1356 39 polyplex polyplex NN cord-014597-66vd2mdu 1356 40 formed form VBN cord-014597-66vd2mdu 1356 41 spontaneously spontaneously RB cord-014597-66vd2mdu 1356 42 [ [ -LRB- cord-014597-66vd2mdu 1356 43 4 4 CD cord-014597-66vd2mdu 1356 44 ] ] -RRB- cord-014597-66vd2mdu 1356 45 . . . cord-014597-66vd2mdu 1357 1 Cells cell NNS cord-014597-66vd2mdu 1357 2 were be VBD cord-014597-66vd2mdu 1357 3 seeded seed VBN cord-014597-66vd2mdu 1357 4 24 24 CD cord-014597-66vd2mdu 1357 5 hr hr NN cord-014597-66vd2mdu 1357 6 in in IN cord-014597-66vd2mdu 1357 7 CHOMACS CHOMACS NNP cord-014597-66vd2mdu 1357 8 CD CD NNP cord-014597-66vd2mdu 1357 9 media medium NNS cord-014597-66vd2mdu 1357 10 before before IN cord-014597-66vd2mdu 1357 11 transfection transfection NN cord-014597-66vd2mdu 1357 12 . . . cord-014597-66vd2mdu 1358 1 At at IN cord-014597-66vd2mdu 1358 2 transfection transfection NN cord-014597-66vd2mdu 1358 3 time time NN cord-014597-66vd2mdu 1358 4 point point VBP cord-014597-66vd2mdu 1358 5 an an DT cord-014597-66vd2mdu 1358 6 equal equal JJ cord-014597-66vd2mdu 1358 7 amount amount NN cord-014597-66vd2mdu 1358 8 of of IN cord-014597-66vd2mdu 1358 9 cells cell NNS cord-014597-66vd2mdu 1358 10 were be VBD cord-014597-66vd2mdu 1358 11 resuspended resuspend VBN cord-014597-66vd2mdu 1358 12 in in IN cord-014597-66vd2mdu 1358 13 each each DT cord-014597-66vd2mdu 1358 14 media medium NNS cord-014597-66vd2mdu 1358 15 type type NN cord-014597-66vd2mdu 1358 16 . . . cord-014597-66vd2mdu 1359 1 Transfection Transfection NNP cord-014597-66vd2mdu 1359 2 was be VBD cord-014597-66vd2mdu 1359 3 applied apply VBN cord-014597-66vd2mdu 1359 4 either either CC cord-014597-66vd2mdu 1359 5 insitu insitu JJ cord-014597-66vd2mdu 1359 6 or or CC cord-014597-66vd2mdu 1359 7 conventional conventional JJ cord-014597-66vd2mdu 1360 1 ( ( -LRB- cord-014597-66vd2mdu 1360 2 polyplex polyplex NNP cord-014597-66vd2mdu 1360 3 prepared prepare VBD cord-014597-66vd2mdu 1360 4 in in IN cord-014597-66vd2mdu 1360 5 100 100 CD cord-014597-66vd2mdu 1360 6 μL μL NNS cord-014597-66vd2mdu 1360 7 of of IN cord-014597-66vd2mdu 1360 8 150 150 CD cord-014597-66vd2mdu 1360 9 mM mm CD cord-014597-66vd2mdu 1360 10 NaCl nacl NN cord-014597-66vd2mdu 1360 11 and and CC cord-014597-66vd2mdu 1360 12 incubated incubate VBN cord-014597-66vd2mdu 1360 13 for for IN cord-014597-66vd2mdu 1360 14 20 20 CD cord-014597-66vd2mdu 1360 15 min min NN cord-014597-66vd2mdu 1360 16 . . . cord-014597-66vd2mdu 1360 17 ) ) -RRB- cord-014597-66vd2mdu 1360 18 , , , cord-014597-66vd2mdu 1360 19 media medium NNS cord-014597-66vd2mdu 1360 20 addition addition NN cord-014597-66vd2mdu 1360 21 was be VBD cord-014597-66vd2mdu 1360 22 performed perform VBN cord-014597-66vd2mdu 1360 23 5 5 CD cord-014597-66vd2mdu 1360 24 hours hour NNS cord-014597-66vd2mdu 1360 25 post post NN cord-014597-66vd2mdu 1360 26 - - NN cord-014597-66vd2mdu 1360 27 transfection transfection JJ cord-014597-66vd2mdu 1360 28 ( ( -LRB- cord-014597-66vd2mdu 1360 29 hpt hpt NNP cord-014597-66vd2mdu 1360 30 ) ) -RRB- cord-014597-66vd2mdu 1360 31 . . . cord-014597-66vd2mdu 1361 1 Media media NN cord-014597-66vd2mdu 1361 2 type type NN cord-014597-66vd2mdu 1361 3 and and CC cord-014597-66vd2mdu 1361 4 transfection transfection NN cord-014597-66vd2mdu 1361 5 condition condition NN cord-014597-66vd2mdu 1361 6 were be VBD cord-014597-66vd2mdu 1361 7 illustrated illustrate VBN cord-014597-66vd2mdu 1361 8 in in IN cord-014597-66vd2mdu 1361 9 Table Table NNP cord-014597-66vd2mdu 1361 10 1 1 CD cord-014597-66vd2mdu 1361 11 . . . cord-014597-66vd2mdu 1362 1 Media medium NNS cord-014597-66vd2mdu 1362 2 screen screen NN cord-014597-66vd2mdu 1362 3 result result NN cord-014597-66vd2mdu 1362 4 exhibits exhibit VBZ cord-014597-66vd2mdu 1362 5 the the DT cord-014597-66vd2mdu 1362 6 highest high JJS cord-014597-66vd2mdu 1362 7 transfection transfection NN cord-014597-66vd2mdu 1362 8 efficiency efficiency NN cord-014597-66vd2mdu 1362 9 of of IN cord-014597-66vd2mdu 1362 10 around around IN cord-014597-66vd2mdu 1362 11 50 50 CD cord-014597-66vd2mdu 1362 12 % % NN cord-014597-66vd2mdu 1362 13 transfected transfecte VBN cord-014597-66vd2mdu 1362 14 cells cell NNS cord-014597-66vd2mdu 1362 15 by by IN cord-014597-66vd2mdu 1362 16 Opti Opti NNP cord-014597-66vd2mdu 1362 17 - - HYPH cord-014597-66vd2mdu 1362 18 MEM mem NN cord-014597-66vd2mdu 1362 19 medium medium NN cord-014597-66vd2mdu 1362 20 coming come VBG cord-014597-66vd2mdu 1362 21 along along RB cord-014597-66vd2mdu 1362 22 with with IN cord-014597-66vd2mdu 1362 23 low low JJ cord-014597-66vd2mdu 1362 24 cell cell NN cord-014597-66vd2mdu 1362 25 growth growth NN cord-014597-66vd2mdu 1362 26 and and CC cord-014597-66vd2mdu 1362 27 viability viability NN cord-014597-66vd2mdu 1362 28 . . . cord-014597-66vd2mdu 1363 1 To to TO cord-014597-66vd2mdu 1363 2 improve improve VB cord-014597-66vd2mdu 1363 3 the the DT cord-014597-66vd2mdu 1363 4 transfection transfection NN cord-014597-66vd2mdu 1363 5 efficiency efficiency NN cord-014597-66vd2mdu 1363 6 , , , cord-014597-66vd2mdu 1363 7 basic basic JJ cord-014597-66vd2mdu 1363 8 parameters parameter NNS cord-014597-66vd2mdu 1363 9 including include VBG cord-014597-66vd2mdu 1363 10 cell cell NN cord-014597-66vd2mdu 1363 11 density density NN cord-014597-66vd2mdu 1363 12 , , , cord-014597-66vd2mdu 1363 13 pDNA pdna RB cord-014597-66vd2mdu 1363 14 , , , cord-014597-66vd2mdu 1363 15 and and CC cord-014597-66vd2mdu 1363 16 PEI PEI NNP cord-014597-66vd2mdu 1363 17 concentrations concentration NNS cord-014597-66vd2mdu 1363 18 were be VBD cord-014597-66vd2mdu 1363 19 varied varied JJ cord-014597-66vd2mdu 1363 20 and and CC cord-014597-66vd2mdu 1363 21 higher high JJR cord-014597-66vd2mdu 1363 22 transfection transfection NN cord-014597-66vd2mdu 1363 23 efficiency efficiency NN cord-014597-66vd2mdu 1363 24 was be VBD cord-014597-66vd2mdu 1363 25 reached reach VBN cord-014597-66vd2mdu 1363 26 by by IN cord-014597-66vd2mdu 1363 27 reducing reduce VBG cord-014597-66vd2mdu 1363 28 media medium NNS cord-014597-66vd2mdu 1363 29 or or CC cord-014597-66vd2mdu 1363 30 accordingly accordingly RB cord-014597-66vd2mdu 1363 31 increasing increase VBG cord-014597-66vd2mdu 1363 32 cell cell NN cord-014597-66vd2mdu 1363 33 density density NN cord-014597-66vd2mdu 1363 34 , , , cord-014597-66vd2mdu 1363 35 PEI PEI NNP cord-014597-66vd2mdu 1363 36 and and CC cord-014597-66vd2mdu 1363 37 pDNA pdna JJ cord-014597-66vd2mdu 1363 38 concentration concentration NN cord-014597-66vd2mdu 1363 39 for for IN cord-014597-66vd2mdu 1363 40 transfection transfection NN cord-014597-66vd2mdu 1363 41 . . . cord-014597-66vd2mdu 1364 1 Further further JJ cord-014597-66vd2mdu 1364 2 optimization optimization NN cord-014597-66vd2mdu 1364 3 results result NNS cord-014597-66vd2mdu 1364 4 show show VBP cord-014597-66vd2mdu 1364 5 that that IN cord-014597-66vd2mdu 1364 6 the the DT cord-014597-66vd2mdu 1364 7 transfection transfection NN cord-014597-66vd2mdu 1364 8 of of IN cord-014597-66vd2mdu 1364 9 CHO CHO NNP cord-014597-66vd2mdu 1364 10 - - HYPH cord-014597-66vd2mdu 1364 11 K1 K1 NNP cord-014597-66vd2mdu 1364 12 cells cell NNS cord-014597-66vd2mdu 1364 13 in in IN cord-014597-66vd2mdu 1364 14 Opti Opti NNP cord-014597-66vd2mdu 1364 15 - - HYPH cord-014597-66vd2mdu 1364 16 MEM mem NN cord-014597-66vd2mdu 1364 17 ( ( -LRB- cord-014597-66vd2mdu 1364 18 transfection transfection NN cord-014597-66vd2mdu 1364 19 medium medium NN cord-014597-66vd2mdu 1364 20 ) ) -RRB- cord-014597-66vd2mdu 1364 21 for for IN cord-014597-66vd2mdu 1364 22 5 5 CD cord-014597-66vd2mdu 1364 23 hours hour NNS cord-014597-66vd2mdu 1364 24 followed follow VBN cord-014597-66vd2mdu 1364 25 by by IN cord-014597-66vd2mdu 1364 26 addition addition NN cord-014597-66vd2mdu 1364 27 of of IN cord-014597-66vd2mdu 1364 28 CHO CHO NNP cord-014597-66vd2mdu 1364 29 - - HYPH cord-014597-66vd2mdu 1364 30 MACS MACS NNP cord-014597-66vd2mdu 1364 31 CD cd NN cord-014597-66vd2mdu 1364 32 ( ( -LRB- cord-014597-66vd2mdu 1364 33 production production NN cord-014597-66vd2mdu 1364 34 medium medium NN cord-014597-66vd2mdu 1364 35 ) ) -RRB- cord-014597-66vd2mdu 1364 36 for for IN cord-014597-66vd2mdu 1364 37 further further RB cord-014597-66vd2mdu 1364 38 enhancing enhance VBG cord-014597-66vd2mdu 1364 39 the the DT cord-014597-66vd2mdu 1364 40 transfection transfection NN cord-014597-66vd2mdu 1364 41 , , , cord-014597-66vd2mdu 1364 42 cell cell NN cord-014597-66vd2mdu 1364 43 count count NN cord-014597-66vd2mdu 1364 44 , , , cord-014597-66vd2mdu 1364 45 and and CC cord-014597-66vd2mdu 1364 46 cell cell NN cord-014597-66vd2mdu 1364 47 viability viability NN cord-014597-66vd2mdu 1364 48 . . . cord-014597-66vd2mdu 1365 1 The the DT cord-014597-66vd2mdu 1365 2 transfection transfection NN cord-014597-66vd2mdu 1365 3 efficiency efficiency NN cord-014597-66vd2mdu 1365 4 ( ( -LRB- cord-014597-66vd2mdu 1365 5 TE TE NNP cord-014597-66vd2mdu 1365 6 ) ) -RRB- cord-014597-66vd2mdu 1365 7 increased increase VBD cord-014597-66vd2mdu 1365 8 up up IN cord-014597-66vd2mdu 1365 9 to to IN cord-014597-66vd2mdu 1365 10 85 85 CD cord-014597-66vd2mdu 1365 11 ± ± CD cord-014597-66vd2mdu 1365 12 2.6 2.6 CD cord-014597-66vd2mdu 1365 13 % % NN cord-014597-66vd2mdu 1365 14 coincide coincide NN cord-014597-66vd2mdu 1365 15 with with IN cord-014597-66vd2mdu 1365 16 increases increase NNS cord-014597-66vd2mdu 1365 17 in in IN cord-014597-66vd2mdu 1365 18 viable viable JJ cord-014597-66vd2mdu 1365 19 cell cell NN cord-014597-66vd2mdu 1365 20 concentration concentration NN cord-014597-66vd2mdu 1365 21 ( ( -LRB- cord-014597-66vd2mdu 1365 22 VCC VCC NNP cord-014597-66vd2mdu 1365 23 ) ) -RRB- cord-014597-66vd2mdu 1365 24 in in IN cord-014597-66vd2mdu 1365 25 comparsion comparsion NN cord-014597-66vd2mdu 1365 26 to to IN cord-014597-66vd2mdu 1365 27 transfection transfection NN cord-014597-66vd2mdu 1365 28 and and CC cord-014597-66vd2mdu 1365 29 cultivation cultivation NN cord-014597-66vd2mdu 1365 30 in in IN cord-014597-66vd2mdu 1365 31 Opti opti JJ cord-014597-66vd2mdu 1365 32 - - HYPH cord-014597-66vd2mdu 1365 33 MEM mem NN cord-014597-66vd2mdu 1365 34 media medium NNS cord-014597-66vd2mdu 1365 35 alone alone RB cord-014597-66vd2mdu 1366 1 Fig Fig NNP cord-014597-66vd2mdu 1366 2 . . . cord-014597-66vd2mdu 1366 3 1a 1a CD cord-014597-66vd2mdu 1366 4 . . . cord-014597-66vd2mdu 1367 1 Both both DT cord-014597-66vd2mdu 1367 2 conventional conventional JJ cord-014597-66vd2mdu 1367 3 and and CC cord-014597-66vd2mdu 1367 4 insitu insitu JJ cord-014597-66vd2mdu 1367 5 methods method NNS cord-014597-66vd2mdu 1367 6 are be VBP cord-014597-66vd2mdu 1367 7 successfully successfully RB cord-014597-66vd2mdu 1367 8 transfected transfecte VBN cord-014597-66vd2mdu 1367 9 CHO CHO NNP cord-014597-66vd2mdu 1367 10 - - HYPH cord-014597-66vd2mdu 1367 11 K1 K1 NNP cord-014597-66vd2mdu 1367 12 to to IN cord-014597-66vd2mdu 1367 13 the the DT cord-014597-66vd2mdu 1367 14 same same JJ cord-014597-66vd2mdu 1367 15 similar similar JJ cord-014597-66vd2mdu 1367 16 high high JJ cord-014597-66vd2mdu 1367 17 TE TE NNP cord-014597-66vd2mdu 1367 18 as as IN cord-014597-66vd2mdu 1367 19 shown show VBN cord-014597-66vd2mdu 1367 20 in in IN cord-014597-66vd2mdu 1367 21 fluorescence fluorescence NN cord-014597-66vd2mdu 1367 22 microscope microscope NN cord-014597-66vd2mdu 1367 23 images image NNS cord-014597-66vd2mdu 1367 24 of of IN cord-014597-66vd2mdu 1367 25 Fig Fig NNP cord-014597-66vd2mdu 1367 26 . . . cord-014597-66vd2mdu 1368 1 1b 1b LS cord-014597-66vd2mdu 1368 2 . . . cord-014597-66vd2mdu 1369 1 Insitu Insitu NNP cord-014597-66vd2mdu 1369 2 transfection transfection NN cord-014597-66vd2mdu 1369 3 shows show VBZ cord-014597-66vd2mdu 1369 4 super super JJ cord-014597-66vd2mdu 1369 5 - - NN cord-014597-66vd2mdu 1369 6 priority priority NN cord-014597-66vd2mdu 1369 7 for for IN cord-014597-66vd2mdu 1369 8 suspension suspension NN cord-014597-66vd2mdu 1369 9 cell cell NN cord-014597-66vd2mdu 1369 10 transfection transfection NN cord-014597-66vd2mdu 1369 11 concerning concern VBG cord-014597-66vd2mdu 1369 12 the the DT cord-014597-66vd2mdu 1369 13 reduction reduction NN cord-014597-66vd2mdu 1369 14 of of IN cord-014597-66vd2mdu 1369 15 handling handling NN cord-014597-66vd2mdu 1369 16 steps step NNS cord-014597-66vd2mdu 1369 17 ( ( -LRB- cord-014597-66vd2mdu 1369 18 one one CD cord-014597-66vd2mdu 1369 19 step step NN cord-014597-66vd2mdu 1369 20 ) ) -RRB- cord-014597-66vd2mdu 1369 21 compared compare VBN cord-014597-66vd2mdu 1369 22 to to IN cord-014597-66vd2mdu 1369 23 the the DT cord-014597-66vd2mdu 1369 24 conventional conventional JJ cord-014597-66vd2mdu 1369 25 way way NN cord-014597-66vd2mdu 1369 26 ( ( -LRB- cord-014597-66vd2mdu 1369 27 two two CD cord-014597-66vd2mdu 1369 28 steps step NNS cord-014597-66vd2mdu 1369 29 ) ) -RRB- cord-014597-66vd2mdu 1369 30 . . . cord-014597-66vd2mdu 1370 1 The the DT cord-014597-66vd2mdu 1370 2 insitu insitu JJ cord-014597-66vd2mdu 1370 3 transfection transfection NN cord-014597-66vd2mdu 1370 4 avoiding avoid VBG cord-014597-66vd2mdu 1370 5 the the DT cord-014597-66vd2mdu 1370 6 optimization optimization NN cord-014597-66vd2mdu 1370 7 step step NN cord-014597-66vd2mdu 1370 8 required require VBN cord-014597-66vd2mdu 1370 9 for for IN cord-014597-66vd2mdu 1370 10 the the DT cord-014597-66vd2mdu 1370 11 incubation incubation NN cord-014597-66vd2mdu 1370 12 period period NN cord-014597-66vd2mdu 1370 13 to to TO cord-014597-66vd2mdu 1370 14 prepare prepare VB cord-014597-66vd2mdu 1370 15 transfection transfection NN cord-014597-66vd2mdu 1370 16 polyplex polyplex NN cord-014597-66vd2mdu 1370 17 but but CC cord-014597-66vd2mdu 1370 18 require require VBP cord-014597-66vd2mdu 1370 19 a a DT cord-014597-66vd2mdu 1370 20 higher high JJR cord-014597-66vd2mdu 1370 21 amount amount NN cord-014597-66vd2mdu 1370 22 of of IN cord-014597-66vd2mdu 1370 23 pDNA pdna NN cord-014597-66vd2mdu 1370 24 and and CC cord-014597-66vd2mdu 1370 25 PEI PEI NNP cord-014597-66vd2mdu 1370 26 than than IN cord-014597-66vd2mdu 1370 27 conventional conventional JJ cord-014597-66vd2mdu 1370 28 way way NN cord-014597-66vd2mdu 1370 29 as as IN cord-014597-66vd2mdu 1370 30 shown show VBN cord-014597-66vd2mdu 1370 31 in in IN cord-014597-66vd2mdu 1370 32 Table Table NNP cord-014597-66vd2mdu 1370 33 1 1 CD cord-014597-66vd2mdu 1370 34 . . . cord-014597-66vd2mdu 1371 1 In in IN cord-014597-66vd2mdu 1371 2 order order NN cord-014597-66vd2mdu 1371 3 to to TO cord-014597-66vd2mdu 1371 4 deal deal VB cord-014597-66vd2mdu 1371 5 with with IN cord-014597-66vd2mdu 1371 6 the the DT cord-014597-66vd2mdu 1371 7 growing grow VBG cord-014597-66vd2mdu 1371 8 demand demand NN cord-014597-66vd2mdu 1371 9 of of IN cord-014597-66vd2mdu 1371 10 large large JJ cord-014597-66vd2mdu 1371 11 quantities quantity NNS cord-014597-66vd2mdu 1371 12 of of IN cord-014597-66vd2mdu 1371 13 therapeutic therapeutic JJ cord-014597-66vd2mdu 1371 14 proteins protein NNS cord-014597-66vd2mdu 1371 15 in in IN cord-014597-66vd2mdu 1371 16 a a DT cord-014597-66vd2mdu 1371 17 timely timely JJ cord-014597-66vd2mdu 1371 18 fashion fashion NN cord-014597-66vd2mdu 1371 19 , , , cord-014597-66vd2mdu 1371 20 expression expression NN cord-014597-66vd2mdu 1371 21 systems system NNS cord-014597-66vd2mdu 1371 22 are be VBP cord-014597-66vd2mdu 1371 23 being be VBG cord-014597-66vd2mdu 1371 24 optimized optimize VBN cord-014597-66vd2mdu 1371 25 to to TO cord-014597-66vd2mdu 1371 26 reduce reduce VB cord-014597-66vd2mdu 1371 27 the the DT cord-014597-66vd2mdu 1371 28 time time NN cord-014597-66vd2mdu 1371 29 of of IN cord-014597-66vd2mdu 1371 30 generation generation NN cord-014597-66vd2mdu 1371 31 of of IN cord-014597-66vd2mdu 1371 32 stable stable JJ cord-014597-66vd2mdu 1371 33 clones clone NNS cord-014597-66vd2mdu 1371 34 as as RB cord-014597-66vd2mdu 1371 35 well well RB cord-014597-66vd2mdu 1371 36 as as IN cord-014597-66vd2mdu 1371 37 to to TO cord-014597-66vd2mdu 1371 38 increase increase VB cord-014597-66vd2mdu 1371 39 the the DT cord-014597-66vd2mdu 1371 40 levels level NNS cord-014597-66vd2mdu 1371 41 of of IN cord-014597-66vd2mdu 1371 42 protein protein NN cord-014597-66vd2mdu 1371 43 secretion secretion NN cord-014597-66vd2mdu 1371 44 . . . cord-014597-66vd2mdu 1372 1 This this DT cord-014597-66vd2mdu 1372 2 can can MD cord-014597-66vd2mdu 1372 3 be be VB cord-014597-66vd2mdu 1372 4 achieved achieve VBN cord-014597-66vd2mdu 1372 5 by by IN cord-014597-66vd2mdu 1372 6 a a DT cord-014597-66vd2mdu 1372 7 combination combination NN cord-014597-66vd2mdu 1372 8 of of IN cord-014597-66vd2mdu 1372 9 expression expression NN cord-014597-66vd2mdu 1372 10 cassette cassette NN cord-014597-66vd2mdu 1372 11 optimization optimization NN cord-014597-66vd2mdu 1372 12 , , , cord-014597-66vd2mdu 1372 13 cell cell NN cord-014597-66vd2mdu 1372 14 engineering engineering NN cord-014597-66vd2mdu 1372 15 and and CC cord-014597-66vd2mdu 1372 16 selection selection NN cord-014597-66vd2mdu 1372 17 process process NN cord-014597-66vd2mdu 1372 18 . . . cord-014597-66vd2mdu 1373 1 We -PRON- PRP cord-014597-66vd2mdu 1373 2 have have VBP cord-014597-66vd2mdu 1373 3 previously previously RB cord-014597-66vd2mdu 1373 4 developed develop VBN cord-014597-66vd2mdu 1373 5 the the DT cord-014597-66vd2mdu 1373 6 cumate cumate NN cord-014597-66vd2mdu 1373 7 gene gene NN cord-014597-66vd2mdu 1373 8 - - HYPH cord-014597-66vd2mdu 1373 9 switch switch NN cord-014597-66vd2mdu 1373 10 , , , cord-014597-66vd2mdu 1373 11 which which WDT cord-014597-66vd2mdu 1373 12 is be VBZ cord-014597-66vd2mdu 1373 13 a a DT cord-014597-66vd2mdu 1373 14 very very RB cord-014597-66vd2mdu 1373 15 efficient efficient JJ cord-014597-66vd2mdu 1373 16 expression expression NN cord-014597-66vd2mdu 1373 17 system system NN cord-014597-66vd2mdu 1373 18 for for IN cord-014597-66vd2mdu 1373 19 protein protein NN cord-014597-66vd2mdu 1373 20 production production NN cord-014597-66vd2mdu 1373 21 [ [ -LRB- cord-014597-66vd2mdu 1373 22 1 1 CD cord-014597-66vd2mdu 1373 23 ] ] -RRB- cord-014597-66vd2mdu 1373 24 . . . cord-014597-66vd2mdu 1374 1 We -PRON- PRP cord-014597-66vd2mdu 1374 2 have have VBP cord-014597-66vd2mdu 1374 3 shown show VBN cord-014597-66vd2mdu 1374 4 that that IN cord-014597-66vd2mdu 1374 5 the the DT cord-014597-66vd2mdu 1374 6 cumate cumate NN cord-014597-66vd2mdu 1374 7 - - HYPH cord-014597-66vd2mdu 1374 8 inducible inducible JJ cord-014597-66vd2mdu 1374 9 promoter promoter NN cord-014597-66vd2mdu 1374 10 ( ( -LRB- cord-014597-66vd2mdu 1374 11 CR5 CR5 NNP cord-014597-66vd2mdu 1374 12 ) ) -RRB- cord-014597-66vd2mdu 1374 13 was be VBD cord-014597-66vd2mdu 1374 14 the the DT cord-014597-66vd2mdu 1374 15 strongest strong JJS cord-014597-66vd2mdu 1374 16 promoter promoter NN cord-014597-66vd2mdu 1374 17 we -PRON- PRP cord-014597-66vd2mdu 1374 18 had have VBD cord-014597-66vd2mdu 1374 19 tested test VBN cord-014597-66vd2mdu 1374 20 so so RB cord-014597-66vd2mdu 1374 21 far far RB cord-014597-66vd2mdu 1374 22 in in IN cord-014597-66vd2mdu 1374 23 Chinese chinese JJ cord-014597-66vd2mdu 1374 24 hamster hamster NN cord-014597-66vd2mdu 1374 25 ovary ovary NN cord-014597-66vd2mdu 1374 26 ( ( -LRB- cord-014597-66vd2mdu 1374 27 CHO CHO NNP cord-014597-66vd2mdu 1374 28 ) ) -RRB- cord-014597-66vd2mdu 1374 29 cells cell NNS cord-014597-66vd2mdu 1374 30 . . . cord-014597-66vd2mdu 1375 1 With with IN cord-014597-66vd2mdu 1375 2 this this DT cord-014597-66vd2mdu 1375 3 promoter promoter NN cord-014597-66vd2mdu 1375 4 , , , cord-014597-66vd2mdu 1375 5 we -PRON- PRP cord-014597-66vd2mdu 1375 6 were be VBD cord-014597-66vd2mdu 1375 7 able able JJ cord-014597-66vd2mdu 1375 8 to to TO cord-014597-66vd2mdu 1375 9 generate generate VB cord-014597-66vd2mdu 1375 10 stable stable JJ cord-014597-66vd2mdu 1375 11 CHO CHO NNP cord-014597-66vd2mdu 1375 12 pools pool NNS cord-014597-66vd2mdu 1375 13 capable capable JJ cord-014597-66vd2mdu 1375 14 of of IN cord-014597-66vd2mdu 1375 15 producing produce VBG cord-014597-66vd2mdu 1375 16 high high JJ cord-014597-66vd2mdu 1375 17 levels level NNS cord-014597-66vd2mdu 1375 18 of of IN cord-014597-66vd2mdu 1375 19 a a DT cord-014597-66vd2mdu 1375 20 Fc Fc NNP cord-014597-66vd2mdu 1375 21 fusion fusion NN cord-014597-66vd2mdu 1375 22 protein protein NN cord-014597-66vd2mdu 1375 23 ( ( -LRB- cord-014597-66vd2mdu 1375 24 900 900 CD cord-014597-66vd2mdu 1375 25 mg mg NNP cord-014597-66vd2mdu 1375 26 / / SYM cord-014597-66vd2mdu 1375 27 L L NNP cord-014597-66vd2mdu 1375 28 ) ) -RRB- cord-014597-66vd2mdu 1375 29 , , , cord-014597-66vd2mdu 1375 30 outperforming outperform VBG cord-014597-66vd2mdu 1375 31 by by IN cord-014597-66vd2mdu 1375 32 3 3 CD cord-014597-66vd2mdu 1375 33 to to TO cord-014597-66vd2mdu 1375 34 4 4 CD cord-014597-66vd2mdu 1375 35 fold fold VB cord-014597-66vd2mdu 1375 36 those those DT cord-014597-66vd2mdu 1375 37 generated generate VBN cord-014597-66vd2mdu 1375 38 with with IN cord-014597-66vd2mdu 1375 39 CMV5 CMV5 NNP cord-014597-66vd2mdu 1375 40 and and CC cord-014597-66vd2mdu 1375 41 hybrid hybrid JJ cord-014597-66vd2mdu 1375 42 EF1α EF1α NNP cord-014597-66vd2mdu 1375 43 - - HYPH cord-014597-66vd2mdu 1375 44 HTLV HTLV NNP cord-014597-66vd2mdu 1375 45 constitutive constitutive JJ cord-014597-66vd2mdu 1375 46 promoters promoter NNS cord-014597-66vd2mdu 1375 47 . . . cord-014597-66vd2mdu 1376 1 Besides besides IN cord-014597-66vd2mdu 1376 2 the the DT cord-014597-66vd2mdu 1376 3 strength strength NN cord-014597-66vd2mdu 1376 4 of of IN cord-014597-66vd2mdu 1376 5 the the DT cord-014597-66vd2mdu 1376 6 CR5 CR5 NNP cord-014597-66vd2mdu 1376 7 promoter promoter NN cord-014597-66vd2mdu 1376 8 , , , cord-014597-66vd2mdu 1376 9 we -PRON- PRP cord-014597-66vd2mdu 1376 10 demonstrated demonstrate VBD cord-014597-66vd2mdu 1376 11 that that IN cord-014597-66vd2mdu 1376 12 the the DT cord-014597-66vd2mdu 1376 13 ability ability NN cord-014597-66vd2mdu 1376 14 to to TO cord-014597-66vd2mdu 1376 15 control control VB cord-014597-66vd2mdu 1376 16 both both CC cord-014597-66vd2mdu 1376 17 the the DT cord-014597-66vd2mdu 1376 18 time time NN cord-014597-66vd2mdu 1376 19 and and CC cord-014597-66vd2mdu 1376 20 the the DT cord-014597-66vd2mdu 1376 21 level level NN cord-014597-66vd2mdu 1376 22 of of IN cord-014597-66vd2mdu 1376 23 expression expression NN cord-014597-66vd2mdu 1376 24 during during IN cord-014597-66vd2mdu 1376 25 pool pool NN cord-014597-66vd2mdu 1376 26 generation generation NN cord-014597-66vd2mdu 1376 27 and and CC cord-014597-66vd2mdu 1376 28 maintenance maintenance NN cord-014597-66vd2mdu 1376 29 gave give VBD cord-014597-66vd2mdu 1376 30 a a DT cord-014597-66vd2mdu 1376 31 real real JJ cord-014597-66vd2mdu 1376 32 advantage advantage NN cord-014597-66vd2mdu 1376 33 to to IN cord-014597-66vd2mdu 1376 34 the the DT cord-014597-66vd2mdu 1376 35 inducible inducible JJ cord-014597-66vd2mdu 1376 36 expression expression NN cord-014597-66vd2mdu 1376 37 system system NN cord-014597-66vd2mdu 1376 38 . . . cord-014597-66vd2mdu 1377 1 Indeed indeed RB cord-014597-66vd2mdu 1377 2 , , , cord-014597-66vd2mdu 1377 3 we -PRON- PRP cord-014597-66vd2mdu 1377 4 observed observe VBD cord-014597-66vd2mdu 1377 5 that that IN cord-014597-66vd2mdu 1377 6 keeping keep VBG cord-014597-66vd2mdu 1377 7 the the DT cord-014597-66vd2mdu 1377 8 expression expression NN cord-014597-66vd2mdu 1377 9 OFF off RP cord-014597-66vd2mdu 1377 10 during during IN cord-014597-66vd2mdu 1377 11 selection selection NN cord-014597-66vd2mdu 1377 12 enabled enable VBD cord-014597-66vd2mdu 1377 13 the the DT cord-014597-66vd2mdu 1377 14 generation generation NN cord-014597-66vd2mdu 1377 15 of of IN cord-014597-66vd2mdu 1377 16 pools pool NNS cord-014597-66vd2mdu 1377 17 with with IN cord-014597-66vd2mdu 1377 18 superior superior JJ cord-014597-66vd2mdu 1377 19 productivity productivity NN cord-014597-66vd2mdu 1377 20 compared compare VBN cord-014597-66vd2mdu 1377 21 with with IN cord-014597-66vd2mdu 1377 22 the the DT cord-014597-66vd2mdu 1377 23 pools pool NNS cord-014597-66vd2mdu 1377 24 whose whose WP$ cord-014597-66vd2mdu 1377 25 expression expression NN cord-014597-66vd2mdu 1377 26 was be VBD cord-014597-66vd2mdu 1377 27 maintained maintain VBN cord-014597-66vd2mdu 1377 28 ON on RP cord-014597-66vd2mdu 1377 29 . . . cord-014597-66vd2mdu 1378 1 Moreover moreover RB cord-014597-66vd2mdu 1378 2 , , , cord-014597-66vd2mdu 1378 3 preliminary preliminary JJ cord-014597-66vd2mdu 1378 4 results result NNS cord-014597-66vd2mdu 1378 5 suggest suggest VBP cord-014597-66vd2mdu 1378 6 that that IN cord-014597-66vd2mdu 1378 7 keeping keep VBG cord-014597-66vd2mdu 1378 8 recombinant recombinant JJ cord-014597-66vd2mdu 1378 9 protein protein NN cord-014597-66vd2mdu 1378 10 expression expression NN cord-014597-66vd2mdu 1378 11 down down RP cord-014597-66vd2mdu 1378 12 increases increase VBZ cord-014597-66vd2mdu 1378 13 the the DT cord-014597-66vd2mdu 1378 14 frequency frequency NN cord-014597-66vd2mdu 1378 15 of of IN cord-014597-66vd2mdu 1378 16 high high JJ cord-014597-66vd2mdu 1378 17 producer producer NN cord-014597-66vd2mdu 1378 18 clones clone NNS cord-014597-66vd2mdu 1378 19 [ [ -LRB- cord-014597-66vd2mdu 1378 20 2 2 CD cord-014597-66vd2mdu 1378 21 ] ] -RRB- cord-014597-66vd2mdu 1378 22 . . . cord-014597-66vd2mdu 1379 1 Knowing know VBG cord-014597-66vd2mdu 1379 2 that that IN cord-014597-66vd2mdu 1379 3 one one CD cord-014597-66vd2mdu 1379 4 of of IN cord-014597-66vd2mdu 1379 5 the the DT cord-014597-66vd2mdu 1379 6 main main JJ cord-014597-66vd2mdu 1379 7 bottlenecks bottleneck NNS cord-014597-66vd2mdu 1379 8 of of IN cord-014597-66vd2mdu 1379 9 the the DT cord-014597-66vd2mdu 1379 10 successful successful JJ cord-014597-66vd2mdu 1379 11 bioprocessing bioprocessing NN cord-014597-66vd2mdu 1379 12 of of IN cord-014597-66vd2mdu 1379 13 recombinant recombinant JJ cord-014597-66vd2mdu 1379 14 proteins protein NNS cord-014597-66vd2mdu 1379 15 using use VBG cord-014597-66vd2mdu 1379 16 CHO CHO NNP cord-014597-66vd2mdu 1379 17 cells cell NNS cord-014597-66vd2mdu 1379 18 is be VBZ cord-014597-66vd2mdu 1379 19 the the DT cord-014597-66vd2mdu 1379 20 rapid rapid JJ cord-014597-66vd2mdu 1379 21 isolation isolation NN cord-014597-66vd2mdu 1379 22 of of IN cord-014597-66vd2mdu 1379 23 a a DT cord-014597-66vd2mdu 1379 24 high high JJ cord-014597-66vd2mdu 1379 25 producer producer NN cord-014597-66vd2mdu 1379 26 , , , cord-014597-66vd2mdu 1379 27 our -PRON- PRP$ cord-014597-66vd2mdu 1379 28 data datum NNS cord-014597-66vd2mdu 1379 29 suggest suggest VBP cord-014597-66vd2mdu 1379 30 that that IN cord-014597-66vd2mdu 1379 31 the the DT cord-014597-66vd2mdu 1379 32 cumate cumate NNP cord-014597-66vd2mdu 1379 33 gene gene NN cord-014597-66vd2mdu 1379 34 - - HYPH cord-014597-66vd2mdu 1379 35 switch switch NN cord-014597-66vd2mdu 1379 36 system system NN cord-014597-66vd2mdu 1379 37 could could MD cord-014597-66vd2mdu 1379 38 be be VB cord-014597-66vd2mdu 1379 39 a a DT cord-014597-66vd2mdu 1379 40 valuable valuable JJ cord-014597-66vd2mdu 1379 41 platform platform NN cord-014597-66vd2mdu 1379 42 for for IN cord-014597-66vd2mdu 1379 43 the the DT cord-014597-66vd2mdu 1379 44 generation generation NN cord-014597-66vd2mdu 1379 45 of of IN cord-014597-66vd2mdu 1379 46 stable stable JJ cord-014597-66vd2mdu 1379 47 clones clone NNS cord-014597-66vd2mdu 1379 48 . . . cord-014597-66vd2mdu 1380 1 The the DT cord-014597-66vd2mdu 1380 2 main main JJ cord-014597-66vd2mdu 1380 3 regulatory regulatory JJ cord-014597-66vd2mdu 1380 4 authorities authority NNS cord-014597-66vd2mdu 1380 5 and and CC cord-014597-66vd2mdu 1380 6 organizations organization NNS cord-014597-66vd2mdu 1380 7 demand demand VBP cord-014597-66vd2mdu 1380 8 proof proof NN cord-014597-66vd2mdu 1380 9 of of IN cord-014597-66vd2mdu 1380 10 monoclonality monoclonality NN cord-014597-66vd2mdu 1380 11 for for IN cord-014597-66vd2mdu 1380 12 biotechnological biotechnological JJ cord-014597-66vd2mdu 1380 13 producer producer NN cord-014597-66vd2mdu 1380 14 cells cell NNS cord-014597-66vd2mdu 1380 15 . . . cord-014597-66vd2mdu 1381 1 With with IN cord-014597-66vd2mdu 1381 2 increasing increase VBG cord-014597-66vd2mdu 1381 3 pressure pressure NN cord-014597-66vd2mdu 1381 4 to to TO cord-014597-66vd2mdu 1381 5 shorten shorten VB cord-014597-66vd2mdu 1381 6 timelines timeline NNS cord-014597-66vd2mdu 1381 7 and and CC cord-014597-66vd2mdu 1381 8 to to TO cord-014597-66vd2mdu 1381 9 improve improve VB cord-014597-66vd2mdu 1381 10 drug drug NN cord-014597-66vd2mdu 1381 11 safety safety NN cord-014597-66vd2mdu 1381 12 , , , cord-014597-66vd2mdu 1381 13 technologically technologically RB cord-014597-66vd2mdu 1381 14 advanced advanced JJ cord-014597-66vd2mdu 1381 15 methods method NNS cord-014597-66vd2mdu 1381 16 have have VBP cord-014597-66vd2mdu 1381 17 to to TO cord-014597-66vd2mdu 1381 18 be be VB cord-014597-66vd2mdu 1381 19 established establish VBN cord-014597-66vd2mdu 1381 20 to to TO cord-014597-66vd2mdu 1381 21 ensure ensure VB cord-014597-66vd2mdu 1381 22 that that IN cord-014597-66vd2mdu 1381 23 production production NN cord-014597-66vd2mdu 1381 24 cell cell NN cord-014597-66vd2mdu 1381 25 lines line NNS cord-014597-66vd2mdu 1381 26 are be VBP cord-014597-66vd2mdu 1381 27 derived derive VBN cord-014597-66vd2mdu 1381 28 from from IN cord-014597-66vd2mdu 1381 29 a a DT cord-014597-66vd2mdu 1381 30 single single JJ cord-014597-66vd2mdu 1381 31 progenitor progenitor NN cord-014597-66vd2mdu 1381 32 cell cell NN cord-014597-66vd2mdu 1381 33 . . . cord-014597-66vd2mdu 1382 1 Sartorius Sartorius NNP cord-014597-66vd2mdu 1382 2 Stedim Stedim NNP cord-014597-66vd2mdu 1382 3 Cellca Cellca NNP cord-014597-66vd2mdu 1382 4 's 's POS cord-014597-66vd2mdu 1382 5 single single JJ cord-014597-66vd2mdu 1382 6 cell cell NN cord-014597-66vd2mdu 1382 7 cloning cloning NN cord-014597-66vd2mdu 1382 8 approach approach NN cord-014597-66vd2mdu 1382 9 is be VBZ cord-014597-66vd2mdu 1382 10 based base VBN cord-014597-66vd2mdu 1382 11 on on IN cord-014597-66vd2mdu 1382 12 one one CD cord-014597-66vd2mdu 1382 13 round round NN cord-014597-66vd2mdu 1382 14 of of IN cord-014597-66vd2mdu 1382 15 fluorescence fluorescence NN cord-014597-66vd2mdu 1382 16 - - HYPH cord-014597-66vd2mdu 1382 17 activated activate VBN cord-014597-66vd2mdu 1382 18 cell cell NN cord-014597-66vd2mdu 1382 19 sorting sorting NN cord-014597-66vd2mdu 1382 20 ( ( -LRB- cord-014597-66vd2mdu 1382 21 FACS FACS NNP cord-014597-66vd2mdu 1382 22 ) ) -RRB- cord-014597-66vd2mdu 1382 23 using use VBG cord-014597-66vd2mdu 1382 24 Becton Becton NNP cord-014597-66vd2mdu 1382 25 Dickinson Dickinson NNP cord-014597-66vd2mdu 1382 26 ( ( -LRB- cord-014597-66vd2mdu 1382 27 BD BD NNP cord-014597-66vd2mdu 1382 28 ) ) -RRB- cord-014597-66vd2mdu 1383 1 FACSAriaTM FACSAriaTM NNP cord-014597-66vd2mdu 1383 2 Fusion Fusion NNP cord-014597-66vd2mdu 1383 3 cell cell NN cord-014597-66vd2mdu 1383 4 sorter sorter NN cord-014597-66vd2mdu 1383 5 combined combine VBN cord-014597-66vd2mdu 1383 6 with with IN cord-014597-66vd2mdu 1383 7 photodocumentation photodocumentation NN cord-014597-66vd2mdu 1383 8 by by IN cord-014597-66vd2mdu 1383 9 SynenTec SynenTec NNP cord-014597-66vd2mdu 1383 10 Cellavista Cellavista NNP cord-014597-66vd2mdu 1383 11 microscopic microscopic JJ cord-014597-66vd2mdu 1383 12 imaging imaging NN cord-014597-66vd2mdu 1383 13 system system NN cord-014597-66vd2mdu 1383 14 . . . cord-014597-66vd2mdu 1384 1 For for IN cord-014597-66vd2mdu 1384 2 the the DT cord-014597-66vd2mdu 1384 3 approach approach NN cord-014597-66vd2mdu 1384 4 , , , cord-014597-66vd2mdu 1384 5 critical critical JJ cord-014597-66vd2mdu 1384 6 process process NN cord-014597-66vd2mdu 1384 7 parameters parameter NNS cord-014597-66vd2mdu 1384 8 such such JJ cord-014597-66vd2mdu 1384 9 as as IN cord-014597-66vd2mdu 1384 10 different different JJ cord-014597-66vd2mdu 1384 11 cell cell NN cord-014597-66vd2mdu 1384 12 lines line NNS cord-014597-66vd2mdu 1384 13 , , , cord-014597-66vd2mdu 1384 14 viability viability NN cord-014597-66vd2mdu 1384 15 and and CC cord-014597-66vd2mdu 1384 16 cell cell NN cord-014597-66vd2mdu 1384 17 aggregation aggregation NN cord-014597-66vd2mdu 1384 18 levels level NNS cord-014597-66vd2mdu 1384 19 were be VBD cord-014597-66vd2mdu 1384 20 investigated investigate VBN cord-014597-66vd2mdu 1384 21 separately separately RB cord-014597-66vd2mdu 1384 22 to to TO cord-014597-66vd2mdu 1384 23 assess assess VB cord-014597-66vd2mdu 1384 24 their -PRON- PRP$ cord-014597-66vd2mdu 1384 25 contribution contribution NN cord-014597-66vd2mdu 1384 26 to to IN cord-014597-66vd2mdu 1384 27 the the DT cord-014597-66vd2mdu 1384 28 probability probability NN cord-014597-66vd2mdu 1384 29 of of IN cord-014597-66vd2mdu 1384 30 monoclonality monoclonality NN cord-014597-66vd2mdu 1384 31 . . . cord-014597-66vd2mdu 1385 1 Immediately immediately RB cord-014597-66vd2mdu 1385 2 after after IN cord-014597-66vd2mdu 1385 3 single single JJ cord-014597-66vd2mdu 1385 4 cell cell NN cord-014597-66vd2mdu 1385 5 cloning clone VBG cord-014597-66vd2mdu 1385 6 into into IN cord-014597-66vd2mdu 1385 7 384-well 384-well CD cord-014597-66vd2mdu 1385 8 plates plate NNS cord-014597-66vd2mdu 1385 9 ( ( -LRB- cord-014597-66vd2mdu 1386 1 1 1 LS cord-014597-66vd2mdu 1386 2 cell/ cell/ NN cord-014597-66vd2mdu 1386 3 well well NN cord-014597-66vd2mdu 1386 4 ) ) -RRB- cord-014597-66vd2mdu 1387 1 the the DT cord-014597-66vd2mdu 1387 2 plates plate NNS cord-014597-66vd2mdu 1387 3 were be VBD cord-014597-66vd2mdu 1387 4 centrifuged centrifuge VBN cord-014597-66vd2mdu 1387 5 followed follow VBN cord-014597-66vd2mdu 1387 6 by by IN cord-014597-66vd2mdu 1387 7 imaging image VBG cord-014597-66vd2mdu 1387 8 using use VBG cord-014597-66vd2mdu 1387 9 the the DT cord-014597-66vd2mdu 1387 10 Cellavista Cellavista NNP cord-014597-66vd2mdu 1387 11 ( ( -LRB- cord-014597-66vd2mdu 1387 12 day day NN cord-014597-66vd2mdu 1387 13 0 0 CD cord-014597-66vd2mdu 1387 14 ) ) -RRB- cord-014597-66vd2mdu 1387 15 . . . cord-014597-66vd2mdu 1388 1 Further further JJ cord-014597-66vd2mdu 1388 2 Cellavista cellavista JJ cord-014597-66vd2mdu 1388 3 images image NNS cord-014597-66vd2mdu 1388 4 are be VBP cord-014597-66vd2mdu 1388 5 taken take VBN cord-014597-66vd2mdu 1388 6 on on IN cord-014597-66vd2mdu 1388 7 day day NN cord-014597-66vd2mdu 1388 8 1 1 CD cord-014597-66vd2mdu 1388 9 , , , cord-014597-66vd2mdu 1388 10 day day NN cord-014597-66vd2mdu 1388 11 2 2 CD cord-014597-66vd2mdu 1388 12 and and CC cord-014597-66vd2mdu 1388 13 on on IN cord-014597-66vd2mdu 1388 14 one one CD cord-014597-66vd2mdu 1388 15 day day NN cord-014597-66vd2mdu 1388 16 between between IN cord-014597-66vd2mdu 1388 17 day day NN cord-014597-66vd2mdu 1388 18 5 5 CD cord-014597-66vd2mdu 1388 19 and and CC cord-014597-66vd2mdu 1388 20 7 7 CD cord-014597-66vd2mdu 1388 21 . . . cord-014597-66vd2mdu 1389 1 Outgrowth outgrowth NN cord-014597-66vd2mdu 1389 2 was be VBD cord-014597-66vd2mdu 1389 3 defined define VBN cord-014597-66vd2mdu 1389 4 at at IN cord-014597-66vd2mdu 1389 5 day day NN cord-014597-66vd2mdu 1389 6 14 14 CD cord-014597-66vd2mdu 1389 7 . . . cord-014597-66vd2mdu 1390 1 8 8 CD cord-014597-66vd2mdu 1390 2 cell cell NN cord-014597-66vd2mdu 1390 3 lines line NNS cord-014597-66vd2mdu 1390 4 expressing express VBG cord-014597-66vd2mdu 1390 5 different different JJ cord-014597-66vd2mdu 1390 6 recombinant recombinant JJ cord-014597-66vd2mdu 1390 7 products product NNS cord-014597-66vd2mdu 1390 8 were be VBD cord-014597-66vd2mdu 1390 9 investigated investigate VBN cord-014597-66vd2mdu 1390 10 to to TO cord-014597-66vd2mdu 1390 11 calculate calculate VB cord-014597-66vd2mdu 1390 12 probability probability NN cord-014597-66vd2mdu 1390 13 of of IN cord-014597-66vd2mdu 1390 14 having have VBG cord-014597-66vd2mdu 1390 15 ≥ ≥ CD cord-014597-66vd2mdu 1390 16 2 2 CD cord-014597-66vd2mdu 1390 17 cells cell NNS cord-014597-66vd2mdu 1390 18 / / SYM cord-014597-66vd2mdu 1390 19 well well RB cord-014597-66vd2mdu 1390 20 after after IN cord-014597-66vd2mdu 1390 21 FACS FACS NNP cord-014597-66vd2mdu 1390 22 sorting sort VBG cord-014597-66vd2mdu 1390 23 P(d P(d NNP cord-014597-66vd2mdu 1390 24 ) ) -RRB- cord-014597-66vd2mdu 1390 25 , , , cord-014597-66vd2mdu 1390 26 the the DT cord-014597-66vd2mdu 1390 27 apparent apparent JJ cord-014597-66vd2mdu 1390 28 probability probability NN cord-014597-66vd2mdu 1390 29 P(i P(i NNP cord-014597-66vd2mdu 1390 30 ) ) -RRB- cord-014597-66vd2mdu 1390 31 of of IN cord-014597-66vd2mdu 1390 32 having have VBG cord-014597-66vd2mdu 1390 33 ghostcells ghostcell NNS cord-014597-66vd2mdu 1390 34 ( ( -LRB- cord-014597-66vd2mdu 1390 35 cells cell NNS cord-014597-66vd2mdu 1390 36 that that WDT cord-014597-66vd2mdu 1390 37 are be VBP cord-014597-66vd2mdu 1390 38 out out RB cord-014597-66vd2mdu 1390 39 - - HYPH cord-014597-66vd2mdu 1390 40 of of IN cord-014597-66vd2mdu 1390 41 - - HYPH cord-014597-66vd2mdu 1390 42 focus focus NN cord-014597-66vd2mdu 1390 43 and and CC cord-014597-66vd2mdu 1390 44 , , , cord-014597-66vd2mdu 1390 45 thus thus RB cord-014597-66vd2mdu 1390 46 , , , cord-014597-66vd2mdu 1390 47 are be VBP cord-014597-66vd2mdu 1390 48 not not RB cord-014597-66vd2mdu 1390 49 visible visible JJ cord-014597-66vd2mdu 1390 50 during during IN cord-014597-66vd2mdu 1390 51 initial initial JJ cord-014597-66vd2mdu 1390 52 microscopic microscopic JJ cord-014597-66vd2mdu 1390 53 imaging imaging NN cord-014597-66vd2mdu 1390 54 ) ) -RRB- cord-014597-66vd2mdu 1390 55 , , , cord-014597-66vd2mdu 1390 56 and and CC cord-014597-66vd2mdu 1390 57 the the DT cord-014597-66vd2mdu 1390 58 apparent apparent JJ cord-014597-66vd2mdu 1390 59 probability probability NN cord-014597-66vd2mdu 1390 60 P(k P(k NNP cord-014597-66vd2mdu 1390 61 ) ) -RRB- cord-014597-66vd2mdu 1390 62 of of IN cord-014597-66vd2mdu 1390 63 having have VBG cord-014597-66vd2mdu 1390 64 ghostcells ghostcell NNS cord-014597-66vd2mdu 1390 65 that that WDT cord-014597-66vd2mdu 1390 66 outgrow outgrow VBP cord-014597-66vd2mdu 1390 67 the the DT cord-014597-66vd2mdu 1390 68 384-well 384-well CD cord-014597-66vd2mdu 1390 69 stage stage NN cord-014597-66vd2mdu 1391 1 ( ( -LRB- cord-014597-66vd2mdu 1391 2 Fig Fig NNP cord-014597-66vd2mdu 1391 3 . . NNP cord-014597-66vd2mdu 1391 4 1 1 CD cord-014597-66vd2mdu 1391 5 ) ) -RRB- cord-014597-66vd2mdu 1391 6 . . . cord-014597-66vd2mdu 1392 1 Using use VBG cord-014597-66vd2mdu 1392 2 these these DT cord-014597-66vd2mdu 1392 3 results result NNS cord-014597-66vd2mdu 1392 4 , , , cord-014597-66vd2mdu 1392 5 the the DT cord-014597-66vd2mdu 1392 6 probability probability NN cord-014597-66vd2mdu 1392 7 of of IN cord-014597-66vd2mdu 1392 8 obtaining obtain VBG cord-014597-66vd2mdu 1392 9 a a DT cord-014597-66vd2mdu 1392 10 monoclonal monoclonal JJ cord-014597-66vd2mdu 1392 11 cell cell NN cord-014597-66vd2mdu 1392 12 by by IN cord-014597-66vd2mdu 1392 13 using use VBG cord-014597-66vd2mdu 1392 14 Sartorius Sartorius NNP cord-014597-66vd2mdu 1392 15 Stedim Stedim NNP cord-014597-66vd2mdu 1392 16 Cellca Cellca NNP cord-014597-66vd2mdu 1392 17 's 's POS cord-014597-66vd2mdu 1392 18 single single JJ cord-014597-66vd2mdu 1392 19 cell cell NN cord-014597-66vd2mdu 1392 20 cloning cloning NN cord-014597-66vd2mdu 1392 21 approach approach NN cord-014597-66vd2mdu 1392 22 was be VBD cord-014597-66vd2mdu 1392 23 determined determine VBN cord-014597-66vd2mdu 1392 24 ( ( -LRB- cord-014597-66vd2mdu 1392 25 Table table NN cord-014597-66vd2mdu 1392 26 1 1 CD cord-014597-66vd2mdu 1392 27 ) ) -RRB- cord-014597-66vd2mdu 1392 28 by by IN cord-014597-66vd2mdu 1392 29 Conservative conservative JJ cord-014597-66vd2mdu 1392 30 examination examination NN cord-014597-66vd2mdu 1392 31 : : : cord-014597-66vd2mdu 1392 32 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1392 33 , , , cord-014597-66vd2mdu 1392 34 conservative conservative JJ cord-014597-66vd2mdu 1392 35 ) ) -RRB- cord-014597-66vd2mdu 1392 36 = = NFP cord-014597-66vd2mdu 1393 1 1 1 LS cord-014597-66vd2mdu 1393 2 -(P(d -(p(d ADD cord-014597-66vd2mdu 1393 3 ) ) -RRB- cord-014597-66vd2mdu 1394 1 x x NNP cord-014597-66vd2mdu 1394 2 P(i P(i NNP cord-014597-66vd2mdu 1394 3 ) ) -RRB- cord-014597-66vd2mdu 1394 4 ) ) -RRB- cord-014597-66vd2mdu 1395 1 Realistic realistic JJ cord-014597-66vd2mdu 1395 2 examination examination NN cord-014597-66vd2mdu 1395 3 : : : cord-014597-66vd2mdu 1395 4 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1395 5 , , , cord-014597-66vd2mdu 1395 6 realistic realistic JJ cord-014597-66vd2mdu 1395 7 ) ) -RRB- cord-014597-66vd2mdu 1395 8 = = NFP cord-014597-66vd2mdu 1396 1 1 1 LS cord-014597-66vd2mdu 1396 2 -(P(d -(p(d ADD cord-014597-66vd2mdu 1396 3 ) ) -RRB- cord-014597-66vd2mdu 1397 1 x x NNP cord-014597-66vd2mdu 1397 2 P(k P(k NNP cord-014597-66vd2mdu 1397 3 ) ) -RRB- cord-014597-66vd2mdu 1397 4 ) ) -RRB- cord-014597-66vd2mdu 1398 1 Cell cell NN cord-014597-66vd2mdu 1398 2 pools pool NNS cord-014597-66vd2mdu 1398 3 with with IN cord-014597-66vd2mdu 1398 4 low low JJ cord-014597-66vd2mdu 1398 5 viability viability NN cord-014597-66vd2mdu 1398 6 can can MD cord-014597-66vd2mdu 1398 7 theoretically theoretically RB cord-014597-66vd2mdu 1398 8 impact impact VB cord-014597-66vd2mdu 1398 9 the the DT cord-014597-66vd2mdu 1398 10 probability probability NN cord-014597-66vd2mdu 1398 11 of of IN cord-014597-66vd2mdu 1398 12 monoclonality monoclonality NN cord-014597-66vd2mdu 1398 13 by by IN cord-014597-66vd2mdu 1398 14 e.g. e.g. RB cord-014597-66vd2mdu 1398 15 diminishing diminish VBG cord-014597-66vd2mdu 1398 16 microscopic microscopic JJ cord-014597-66vd2mdu 1398 17 imaging imaging NN cord-014597-66vd2mdu 1398 18 quality quality NN cord-014597-66vd2mdu 1398 19 ( ( -LRB- cord-014597-66vd2mdu 1398 20 cell cell NN cord-014597-66vd2mdu 1398 21 debris debris NN cord-014597-66vd2mdu 1398 22 ) ) -RRB- cord-014597-66vd2mdu 1398 23 . . . cord-014597-66vd2mdu 1399 1 Therefore therefore RB cord-014597-66vd2mdu 1399 2 , , , cord-014597-66vd2mdu 1399 3 pool pool NN cord-014597-66vd2mdu 1399 4 cell cell NN cord-014597-66vd2mdu 1399 5 line line NN cord-014597-66vd2mdu 1399 6 1 1 CD cord-014597-66vd2mdu 1399 7 with with IN cord-014597-66vd2mdu 1399 8 very very RB cord-014597-66vd2mdu 1399 9 low low JJ cord-014597-66vd2mdu 1399 10 viability viability NN cord-014597-66vd2mdu 1399 11 ( ( -LRB- cord-014597-66vd2mdu 1399 12 ≥36 ≥36 VBZ cord-014597-66vd2mdu 1399 13 % % NN cord-014597-66vd2mdu 1399 14 ) ) -RRB- cord-014597-66vd2mdu 1399 15 was be VBD cord-014597-66vd2mdu 1399 16 used use VBN cord-014597-66vd2mdu 1399 17 to to TO cord-014597-66vd2mdu 1399 18 demonstrate demonstrate VB cord-014597-66vd2mdu 1399 19 , , , cord-014597-66vd2mdu 1399 20 that that IN cord-014597-66vd2mdu 1399 21 the the DT cord-014597-66vd2mdu 1399 22 probability probability NN cord-014597-66vd2mdu 1399 23 of of IN cord-014597-66vd2mdu 1399 24 monoclonality monoclonality NN cord-014597-66vd2mdu 1399 25 is be VBZ cord-014597-66vd2mdu 1399 26 still still RB cord-014597-66vd2mdu 1399 27 99.9 99.9 CD cord-014597-66vd2mdu 1399 28 % % NN cord-014597-66vd2mdu 1399 29 in in IN cord-014597-66vd2mdu 1399 30 case case NN cord-014597-66vd2mdu 1399 31 of of IN cord-014597-66vd2mdu 1399 32 low low JJ cord-014597-66vd2mdu 1399 33 viability viability NN cord-014597-66vd2mdu 1399 34 on on IN cord-014597-66vd2mdu 1399 35 day day NN cord-014597-66vd2mdu 1399 36 of of IN cord-014597-66vd2mdu 1399 37 sorting sorting NN cord-014597-66vd2mdu 1399 38 : : : cord-014597-66vd2mdu 1399 39 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1399 40 , , , cord-014597-66vd2mdu 1399 41 conservative conservative JJ cord-014597-66vd2mdu 1399 42 ) ) -RRB- cord-014597-66vd2mdu 1399 43 = = NFP cord-014597-66vd2mdu 1400 1 P(d p(d JJ cord-014597-66vd2mdu 1400 2 ) ) -RRB- cord-014597-66vd2mdu 1401 1 x x NNP cord-014597-66vd2mdu 1401 2 P(i P(i NNP cord-014597-66vd2mdu 1401 3 ) ) -RRB- cord-014597-66vd2mdu 1401 4 = = NFP cord-014597-66vd2mdu 1402 1 99.9 99.9 CD cord-014597-66vd2mdu 1402 2 % % NN cord-014597-66vd2mdu 1402 3 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1402 4 , , , cord-014597-66vd2mdu 1402 5 realistic realistic JJ cord-014597-66vd2mdu 1402 6 ) ) -RRB- cord-014597-66vd2mdu 1403 1 = = SYM cord-014597-66vd2mdu 1403 2 P(d p(d ADD cord-014597-66vd2mdu 1403 3 ) ) -RRB- cord-014597-66vd2mdu 1404 1 x x NNP cord-014597-66vd2mdu 1404 2 P(k P(k NNP cord-014597-66vd2mdu 1404 3 ) ) -RRB- cord-014597-66vd2mdu 1404 4 = = NFP cord-014597-66vd2mdu 1405 1 99.9 99.9 CD cord-014597-66vd2mdu 1405 2 % % NN cord-014597-66vd2mdu 1406 1 Furthermore furthermore RB cord-014597-66vd2mdu 1406 2 , , , cord-014597-66vd2mdu 1406 3 cell cell NN cord-014597-66vd2mdu 1406 4 pools pool NNS cord-014597-66vd2mdu 1406 5 with with IN cord-014597-66vd2mdu 1406 6 high high JJ cord-014597-66vd2mdu 1406 7 aggregation aggregation NN cord-014597-66vd2mdu 1406 8 levels level NNS cord-014597-66vd2mdu 1406 9 can can MD cord-014597-66vd2mdu 1406 10 theoretically theoretically RB cord-014597-66vd2mdu 1406 11 impact impact VB cord-014597-66vd2mdu 1406 12 the the DT cord-014597-66vd2mdu 1406 13 probability probability NN cord-014597-66vd2mdu 1406 14 of of IN cord-014597-66vd2mdu 1406 15 monoclonality monoclonality NN cord-014597-66vd2mdu 1406 16 by by IN cord-014597-66vd2mdu 1406 17 sticking stick VBG cord-014597-66vd2mdu 1406 18 together together RB cord-014597-66vd2mdu 1406 19 during during IN cord-014597-66vd2mdu 1406 20 FACS FACS NNP cord-014597-66vd2mdu 1406 21 sorting sort VBG cord-014597-66vd2mdu 1406 22 and and CC cord-014597-66vd2mdu 1406 23 therefore therefore RB cord-014597-66vd2mdu 1406 24 increase increase VB cord-014597-66vd2mdu 1406 25 the the DT cord-014597-66vd2mdu 1406 26 probability probability NN cord-014597-66vd2mdu 1406 27 P(d p(d JJ cord-014597-66vd2mdu 1406 28 ) ) -RRB- cord-014597-66vd2mdu 1406 29 of of IN cord-014597-66vd2mdu 1406 30 having have VBG cord-014597-66vd2mdu 1406 31 ≥ ≥ CD cord-014597-66vd2mdu 1406 32 2 2 CD cord-014597-66vd2mdu 1406 33 cells cell NNS cord-014597-66vd2mdu 1406 34 / / SYM cord-014597-66vd2mdu 1406 35 droplet droplet NN cord-014597-66vd2mdu 1406 36 . . . cord-014597-66vd2mdu 1407 1 Therefore therefore RB cord-014597-66vd2mdu 1407 2 , , , cord-014597-66vd2mdu 1407 3 pool pool NN cord-014597-66vd2mdu 1407 4 cell cell NN cord-014597-66vd2mdu 1407 5 line line NN cord-014597-66vd2mdu 1407 6 8 8 CD cord-014597-66vd2mdu 1407 7 with with IN cord-014597-66vd2mdu 1407 8 high high JJ cord-014597-66vd2mdu 1407 9 aggregation aggregation NN cord-014597-66vd2mdu 1407 10 levels level NNS cord-014597-66vd2mdu 1407 11 ( ( -LRB- cord-014597-66vd2mdu 1407 12 ≥11.1 ≥11.1 JJR cord-014597-66vd2mdu 1407 13 % % NN cord-014597-66vd2mdu 1407 14 ) ) -RRB- cord-014597-66vd2mdu 1407 15 was be VBD cord-014597-66vd2mdu 1407 16 used use VBN cord-014597-66vd2mdu 1407 17 to to TO cord-014597-66vd2mdu 1407 18 demonstrate demonstrate VB cord-014597-66vd2mdu 1407 19 , , , cord-014597-66vd2mdu 1407 20 that that IN cord-014597-66vd2mdu 1407 21 the the DT cord-014597-66vd2mdu 1407 22 probability probability NN cord-014597-66vd2mdu 1407 23 of of IN cord-014597-66vd2mdu 1407 24 monoclonality monoclonality NN cord-014597-66vd2mdu 1407 25 is be VBZ cord-014597-66vd2mdu 1407 26 still still RB cord-014597-66vd2mdu 1407 27 ≥ ≥ CD cord-014597-66vd2mdu 1407 28 99.9 99.9 CD cord-014597-66vd2mdu 1407 29 % % NN cord-014597-66vd2mdu 1407 30 in in IN cord-014597-66vd2mdu 1407 31 case case NN cord-014597-66vd2mdu 1407 32 of of IN cord-014597-66vd2mdu 1407 33 highly highly RB cord-014597-66vd2mdu 1407 34 aggregated aggregated JJ cord-014597-66vd2mdu 1407 35 cell cell NN cord-014597-66vd2mdu 1407 36 pools pool NNS cord-014597-66vd2mdu 1407 37 on on IN cord-014597-66vd2mdu 1407 38 day day NN cord-014597-66vd2mdu 1407 39 of of IN cord-014597-66vd2mdu 1407 40 sorting sorting NN cord-014597-66vd2mdu 1407 41 : : : cord-014597-66vd2mdu 1407 42 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1407 43 , , , cord-014597-66vd2mdu 1407 44 conservative conservative JJ cord-014597-66vd2mdu 1407 45 ) ) -RRB- cord-014597-66vd2mdu 1407 46 = = NFP cord-014597-66vd2mdu 1408 1 P(d p(d JJ cord-014597-66vd2mdu 1408 2 ) ) -RRB- cord-014597-66vd2mdu 1409 1 x x NNP cord-014597-66vd2mdu 1409 2 P(i P(i NNP cord-014597-66vd2mdu 1409 3 ) ) -RRB- cord-014597-66vd2mdu 1409 4 = = NFP cord-014597-66vd2mdu 1410 1 > > XX cord-014597-66vd2mdu 1411 1 99.9 99.9 CD cord-014597-66vd2mdu 1411 2 % % NN cord-014597-66vd2mdu 1411 3 P(monoclonal p(monoclonal JJ cord-014597-66vd2mdu 1411 4 , , , cord-014597-66vd2mdu 1411 5 realistic realistic JJ cord-014597-66vd2mdu 1411 6 ) ) -RRB- cord-014597-66vd2mdu 1412 1 = = SYM cord-014597-66vd2mdu 1412 2 P(d p(d ADD cord-014597-66vd2mdu 1412 3 ) ) -RRB- cord-014597-66vd2mdu 1413 1 x x NNP cord-014597-66vd2mdu 1413 2 P(k P(k NNP cord-014597-66vd2mdu 1413 3 ) ) -RRB- cord-014597-66vd2mdu 1413 4 = = NFP cord-014597-66vd2mdu 1414 1 > > XX cord-014597-66vd2mdu 1415 1 99.9 99.9 CD cord-014597-66vd2mdu 1415 2 % % NN cord-014597-66vd2mdu 1415 3 Conclusions conclusion NNS cord-014597-66vd2mdu 1416 1 In in IN cord-014597-66vd2mdu 1416 2 summary summary NN cord-014597-66vd2mdu 1416 3 , , , cord-014597-66vd2mdu 1416 4 there there EX cord-014597-66vd2mdu 1416 5 is be VBZ cord-014597-66vd2mdu 1416 6 no no DT cord-014597-66vd2mdu 1416 7 obvious obvious JJ cord-014597-66vd2mdu 1416 8 correlation correlation NN cord-014597-66vd2mdu 1416 9 between between IN cord-014597-66vd2mdu 1416 10 protein protein NN cord-014597-66vd2mdu 1416 11 product product NN cord-014597-66vd2mdu 1416 12 type type NN cord-014597-66vd2mdu 1416 13 and and CC cord-014597-66vd2mdu 1416 14 the the DT cord-014597-66vd2mdu 1416 15 determined determined JJ cord-014597-66vd2mdu 1416 16 probabilities probability NNS cord-014597-66vd2mdu 1416 17 for for IN cord-014597-66vd2mdu 1416 18 monoclonality monoclonality NN cord-014597-66vd2mdu 1416 19 . . . cord-014597-66vd2mdu 1417 1 Furthermore furthermore RB cord-014597-66vd2mdu 1417 2 , , , cord-014597-66vd2mdu 1417 3 pools pool NNS cord-014597-66vd2mdu 1417 4 with with IN cord-014597-66vd2mdu 1417 5 a a DT cord-014597-66vd2mdu 1417 6 viability viability NN cord-014597-66vd2mdu 1417 7 as as RB cord-014597-66vd2mdu 1417 8 low low JJ cord-014597-66vd2mdu 1417 9 as as IN cord-014597-66vd2mdu 1417 10 36 36 CD cord-014597-66vd2mdu 1417 11 % % NN cord-014597-66vd2mdu 1417 12 and and CC cord-014597-66vd2mdu 1417 13 pools pool NNS cord-014597-66vd2mdu 1417 14 with with IN cord-014597-66vd2mdu 1417 15 an an DT cord-014597-66vd2mdu 1417 16 aggregation aggregation NN cord-014597-66vd2mdu 1417 17 level level NN cord-014597-66vd2mdu 1417 18 as as RB cord-014597-66vd2mdu 1417 19 high high JJ cord-014597-66vd2mdu 1417 20 as as IN cord-014597-66vd2mdu 1417 21 11.1 11.1 CD cord-014597-66vd2mdu 1417 22 % % NN cord-014597-66vd2mdu 1417 23 can can MD cord-014597-66vd2mdu 1417 24 be be VB cord-014597-66vd2mdu 1417 25 used use VBN cord-014597-66vd2mdu 1417 26 for for IN cord-014597-66vd2mdu 1417 27 SCC SCC NNP cord-014597-66vd2mdu 1417 28 resulting result VBG cord-014597-66vd2mdu 1417 29 in in IN cord-014597-66vd2mdu 1417 30 acceptable acceptable JJ cord-014597-66vd2mdu 1417 31 probabilities probability NNS cord-014597-66vd2mdu 1417 32 of of IN cord-014597-66vd2mdu 1417 33 monoclonality monoclonality NN cord-014597-66vd2mdu 1417 34 . . . cord-014597-66vd2mdu 1418 1 Background Background NNP cord-014597-66vd2mdu 1418 2 ICH ICH NNP cord-014597-66vd2mdu 1418 3 guidance guidance NN cord-014597-66vd2mdu 1418 4 [ [ -LRB- cord-014597-66vd2mdu 1418 5 1 1 CD cord-014597-66vd2mdu 1418 6 ] ] -RRB- cord-014597-66vd2mdu 1418 7 requires require VBZ cord-014597-66vd2mdu 1418 8 that that IN cord-014597-66vd2mdu 1418 9 any any DT cord-014597-66vd2mdu 1418 10 cell cell NN cord-014597-66vd2mdu 1418 11 line line NN cord-014597-66vd2mdu 1418 12 used use VBN cord-014597-66vd2mdu 1418 13 to to TO cord-014597-66vd2mdu 1418 14 produce produce VB cord-014597-66vd2mdu 1418 15 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 1418 16 originates originate VBZ cord-014597-66vd2mdu 1418 17 from from IN cord-014597-66vd2mdu 1418 18 a a DT cord-014597-66vd2mdu 1418 19 single single JJ cord-014597-66vd2mdu 1418 20 progenitor progenitor NN cord-014597-66vd2mdu 1418 21 cell cell NN cord-014597-66vd2mdu 1418 22 . . . cord-014597-66vd2mdu 1419 1 Recently recently RB cord-014597-66vd2mdu 1419 2 , , , cord-014597-66vd2mdu 1419 3 there there EX cord-014597-66vd2mdu 1419 4 has have VBZ cord-014597-66vd2mdu 1419 5 been be VBN cord-014597-66vd2mdu 1419 6 increased increase VBN cord-014597-66vd2mdu 1419 7 scrutiny scrutiny NN cord-014597-66vd2mdu 1419 8 of of IN cord-014597-66vd2mdu 1419 9 the the DT cord-014597-66vd2mdu 1419 10 method(s method(s NNP cord-014597-66vd2mdu 1419 11 ) ) -RRB- cord-014597-66vd2mdu 1419 12 used use VBD cord-014597-66vd2mdu 1419 13 to to TO cord-014597-66vd2mdu 1419 14 achieve achieve VB cord-014597-66vd2mdu 1419 15 this this DT cord-014597-66vd2mdu 1419 16 requirement requirement NN cord-014597-66vd2mdu 1419 17 . . . cord-014597-66vd2mdu 1420 1 Here here RB cord-014597-66vd2mdu 1420 2 , , , cord-014597-66vd2mdu 1420 3 we -PRON- PRP cord-014597-66vd2mdu 1420 4 review review VBP cord-014597-66vd2mdu 1420 5 the the DT cord-014597-66vd2mdu 1420 6 suitability suitability NN cord-014597-66vd2mdu 1420 7 of of IN cord-014597-66vd2mdu 1420 8 the the DT cord-014597-66vd2mdu 1420 9 legacy legacy NN cord-014597-66vd2mdu 1420 10 capillary capillary NN cord-014597-66vd2mdu 1420 11 aided aid VBD cord-014597-66vd2mdu 1420 12 cell cell NN cord-014597-66vd2mdu 1420 13 cloning cloning NN cord-014597-66vd2mdu 1420 14 ( ( -LRB- cord-014597-66vd2mdu 1420 15 CACC CACC NNP cord-014597-66vd2mdu 1420 16 ) ) -RRB- cord-014597-66vd2mdu 1420 17 method method NN cord-014597-66vd2mdu 1420 18 in in IN cord-014597-66vd2mdu 1420 19 light light NN cord-014597-66vd2mdu 1420 20 of of IN cord-014597-66vd2mdu 1420 21 this this DT cord-014597-66vd2mdu 1420 22 changing change VBG cord-014597-66vd2mdu 1420 23 landscape landscape NN cord-014597-66vd2mdu 1420 24 of of IN cord-014597-66vd2mdu 1420 25 expectations expectation NNS cord-014597-66vd2mdu 1420 26 . . . cord-014597-66vd2mdu 1421 1 The the DT cord-014597-66vd2mdu 1421 2 CACC CACC NNP cord-014597-66vd2mdu 1421 3 method method NN cord-014597-66vd2mdu 1421 4 is be VBZ cord-014597-66vd2mdu 1421 5 based base VBN cord-014597-66vd2mdu 1421 6 on on IN cord-014597-66vd2mdu 1421 7 the the DT cord-014597-66vd2mdu 1421 8 ' ' `` cord-014597-66vd2mdu 1421 9 spotting spot VBG cord-014597-66vd2mdu 1421 10 ' ' '' cord-014597-66vd2mdu 1421 11 technique technique NN cord-014597-66vd2mdu 1421 12 [ [ -LRB- cord-014597-66vd2mdu 1421 13 2 2 CD cord-014597-66vd2mdu 1421 14 ] ] -RRB- cord-014597-66vd2mdu 1421 15 and and CC cord-014597-66vd2mdu 1421 16 relies rely VBZ cord-014597-66vd2mdu 1421 17 on on IN cord-014597-66vd2mdu 1421 18 independent independent JJ cord-014597-66vd2mdu 1421 19 visual visual JJ cord-014597-66vd2mdu 1421 20 conformation conformation NN cord-014597-66vd2mdu 1421 21 by by IN cord-014597-66vd2mdu 1421 22 two two CD cord-014597-66vd2mdu 1421 23 scientists scientist NNS cord-014597-66vd2mdu 1421 24 of of IN cord-014597-66vd2mdu 1421 25 the the DT cord-014597-66vd2mdu 1421 26 presence presence NN cord-014597-66vd2mdu 1421 27 of of IN cord-014597-66vd2mdu 1421 28 a a DT cord-014597-66vd2mdu 1421 29 single single JJ cord-014597-66vd2mdu 1421 30 cell cell NN cord-014597-66vd2mdu 1421 31 in in IN cord-014597-66vd2mdu 1421 32 a a DT cord-014597-66vd2mdu 1421 33 1 1 CD cord-014597-66vd2mdu 1421 34 μL μl NN cord-014597-66vd2mdu 1421 35 droplet droplet NN cord-014597-66vd2mdu 1421 36 . . . cord-014597-66vd2mdu 1422 1 This this DT cord-014597-66vd2mdu 1422 2 method method NN cord-014597-66vd2mdu 1422 3 achieves achieve VBZ cord-014597-66vd2mdu 1422 4 a a DT cord-014597-66vd2mdu 1422 5 high high JJ cord-014597-66vd2mdu 1422 6 probability probability NN cord-014597-66vd2mdu 1422 7 of of IN cord-014597-66vd2mdu 1422 8 monoclonality monoclonality NN cord-014597-66vd2mdu 1422 9 in in IN cord-014597-66vd2mdu 1422 10 one one CD cord-014597-66vd2mdu 1422 11 cloning clone VBG cord-014597-66vd2mdu 1422 12 round round RB cord-014597-66vd2mdu 1422 13 . . . cord-014597-66vd2mdu 1423 1 Although although IN cord-014597-66vd2mdu 1423 2 the the DT cord-014597-66vd2mdu 1423 3 method method NN cord-014597-66vd2mdu 1423 4 has have VBZ cord-014597-66vd2mdu 1423 5 since since IN cord-014597-66vd2mdu 1423 6 been be VBN cord-014597-66vd2mdu 1423 7 replaced replace VBN cord-014597-66vd2mdu 1423 8 by by IN cord-014597-66vd2mdu 1423 9 FACS FACS NNP cord-014597-66vd2mdu 1423 10 single single JJ cord-014597-66vd2mdu 1423 11 cell cell NN cord-014597-66vd2mdu 1423 12 deposition deposition NN cord-014597-66vd2mdu 1423 13 for for IN cord-014597-66vd2mdu 1423 14 routine routine JJ cord-014597-66vd2mdu 1423 15 use use NN cord-014597-66vd2mdu 1423 16 , , , cord-014597-66vd2mdu 1423 17 it -PRON- PRP cord-014597-66vd2mdu 1423 18 remains remain VBZ cord-014597-66vd2mdu 1423 19 a a DT cord-014597-66vd2mdu 1423 20 viable viable JJ cord-014597-66vd2mdu 1423 21 cloning cloning NN cord-014597-66vd2mdu 1423 22 method method NN cord-014597-66vd2mdu 1423 23 . . . cord-014597-66vd2mdu 1424 1 -Performed -performe VBN cord-014597-66vd2mdu 1424 2 by by IN cord-014597-66vd2mdu 1424 3 trained train VBN cord-014597-66vd2mdu 1424 4 scientists scientist NNS cord-014597-66vd2mdu 1424 5 -Dilute -dilute VBP cord-014597-66vd2mdu 1424 6 culture culture NN cord-014597-66vd2mdu 1424 7 to to IN cord-014597-66vd2mdu 1424 8 1500 1500 CD cord-014597-66vd2mdu 1424 9 ± ± NNP cord-014597-66vd2mdu 1424 10 500 500 CD cord-014597-66vd2mdu 1424 11 cells cell NNS cord-014597-66vd2mdu 1424 12 / / SYM cord-014597-66vd2mdu 1424 13 mL ml NN cord-014597-66vd2mdu 1424 14 with with IN cord-014597-66vd2mdu 1424 15 ≤2 ≤2 NNP cord-014597-66vd2mdu 1424 16 % % NN cord-014597-66vd2mdu 1424 17 doublets doublet NNS cord-014597-66vd2mdu 1424 18 -Draw -Draw NNP cord-014597-66vd2mdu 1424 19 cell cell NN cord-014597-66vd2mdu 1424 20 suspension suspension NN cord-014597-66vd2mdu 1424 21 into into IN cord-014597-66vd2mdu 1424 22 pipette pipette NN cord-014597-66vd2mdu 1424 23 tip tip NN cord-014597-66vd2mdu 1424 24 by by IN cord-014597-66vd2mdu 1424 25 capillary capillary JJ cord-014597-66vd2mdu 1424 26 action action NN cord-014597-66vd2mdu 1424 27 ; ; : cord-014597-66vd2mdu 1424 28 tap tap NN cord-014597-66vd2mdu 1424 29 tip tip NN cord-014597-66vd2mdu 1424 30 against against IN cord-014597-66vd2mdu 1424 31 the the DT cord-014597-66vd2mdu 1424 32 centre centre NN cord-014597-66vd2mdu 1424 33 of of IN cord-014597-66vd2mdu 1424 34 the the DT cord-014597-66vd2mdu 1424 35 base base NN cord-014597-66vd2mdu 1424 36 of of IN cord-014597-66vd2mdu 1424 37 each each DT cord-014597-66vd2mdu 1424 38 well well NN cord-014597-66vd2mdu 1424 39 of of IN cord-014597-66vd2mdu 1424 40 a a DT cord-014597-66vd2mdu 1424 41 48 48 CD cord-014597-66vd2mdu 1424 42 well well JJ cord-014597-66vd2mdu 1424 43 plate plate NN cord-014597-66vd2mdu 1424 44 . . . cord-014597-66vd2mdu 1425 1 -Size -Size NNP cord-014597-66vd2mdu 1426 1 of of IN cord-014597-66vd2mdu 1426 2 resulting result VBG cord-014597-66vd2mdu 1426 3 droplet droplet NN cord-014597-66vd2mdu 1426 4 = = NFP cord-014597-66vd2mdu 1426 5 ~1μL ~1μl XX cord-014597-66vd2mdu 1427 1 ( ( -LRB- cord-014597-66vd2mdu 1427 2 Fig Fig NNP cord-014597-66vd2mdu 1427 3 . . . cord-014597-66vd2mdu 1427 4 1a 1a CD cord-014597-66vd2mdu 1427 5 ) ) -RRB- cord-014597-66vd2mdu 1428 1 -Two -Two . cord-014597-66vd2mdu 1429 1 scientists scientist NNS cord-014597-66vd2mdu 1429 2 independently independently RB cord-014597-66vd2mdu 1429 3 view view VBP cord-014597-66vd2mdu 1429 4 all all DT cord-014597-66vd2mdu 1429 5 wells well NNS cord-014597-66vd2mdu 1429 6 using use VBG cord-014597-66vd2mdu 1429 7 a a DT cord-014597-66vd2mdu 1429 8 microscope microscope NN cord-014597-66vd2mdu 1429 9 ( ( -LRB- cord-014597-66vd2mdu 1429 10 initially initially RB cord-014597-66vd2mdu 1429 11 use use VB cord-014597-66vd2mdu 1429 12 40x 40x CD cord-014597-66vd2mdu 1429 13 magnification magnification NN cord-014597-66vd2mdu 1429 14 with with IN cord-014597-66vd2mdu 1429 15 the the DT cord-014597-66vd2mdu 1429 16 entire entire JJ cord-014597-66vd2mdu 1429 17 rim rim NN cord-014597-66vd2mdu 1429 18 of of IN cord-014597-66vd2mdu 1429 19 the the DT cord-014597-66vd2mdu 1429 20 droplet droplet NN cord-014597-66vd2mdu 1429 21 visible visible JJ cord-014597-66vd2mdu 1429 22 within within IN cord-014597-66vd2mdu 1429 23 the the DT cord-014597-66vd2mdu 1429 24 field field NN cord-014597-66vd2mdu 1429 25 - - HYPH cord-014597-66vd2mdu 1429 26 of of IN cord-014597-66vd2mdu 1429 27 - - HYPH cord-014597-66vd2mdu 1429 28 view view NN cord-014597-66vd2mdu 1429 29 . . . cord-014597-66vd2mdu 1430 1 Next next RB cord-014597-66vd2mdu 1430 2 , , , cord-014597-66vd2mdu 1430 3 examine examine VB cord-014597-66vd2mdu 1430 4 particles particle NNS cord-014597-66vd2mdu 1430 5 using use VBG cord-014597-66vd2mdu 1430 6 100x 100x JJR cord-014597-66vd2mdu 1430 7 or or CC cord-014597-66vd2mdu 1430 8 200x 200x CD cord-014597-66vd2mdu 1430 9 magnification magnification NN cord-014597-66vd2mdu 1430 10 to to TO cord-014597-66vd2mdu 1430 11 confirm confirm VB cord-014597-66vd2mdu 1430 12 they -PRON- PRP cord-014597-66vd2mdu 1430 13 are be VBP cord-014597-66vd2mdu 1430 14 cells cell NNS cord-014597-66vd2mdu 1430 15 ) ) -RRB- cord-014597-66vd2mdu 1430 16 and and CC cord-014597-66vd2mdu 1430 17 individually individually RB cord-014597-66vd2mdu 1430 18 record record VB cord-014597-66vd2mdu 1430 19 the the DT cord-014597-66vd2mdu 1430 20 number number NN cord-014597-66vd2mdu 1430 21 of of IN cord-014597-66vd2mdu 1430 22 cells cell NNS cord-014597-66vd2mdu 1430 23 present present JJ cord-014597-66vd2mdu 1430 24 in in IN cord-014597-66vd2mdu 1430 25 each each DT cord-014597-66vd2mdu 1430 26 well well NN cord-014597-66vd2mdu 1430 27 's 's POS cord-014597-66vd2mdu 1430 28 droplet droplet NN cord-014597-66vd2mdu 1430 29 ( ( -LRB- cord-014597-66vd2mdu 1430 30 Fig fig NN cord-014597-66vd2mdu 1430 31 . . . cord-014597-66vd2mdu 1431 1 1b 1b CD cord-014597-66vd2mdu 1431 2 to to IN cord-014597-66vd2mdu 1431 3 d d NN cord-014597-66vd2mdu 1431 4 ) ) -RRB- cord-014597-66vd2mdu 1431 5 . . . cord-014597-66vd2mdu 1432 1 -Exclude -exclude IN cord-014597-66vd2mdu 1432 2 droplet droplet NN cord-014597-66vd2mdu 1432 3 from from IN cord-014597-66vd2mdu 1432 4 further further JJ cord-014597-66vd2mdu 1432 5 analysis analysis NN cord-014597-66vd2mdu 1432 6 if if IN cord-014597-66vd2mdu 1432 7 full full JJ cord-014597-66vd2mdu 1432 8 visualisation visualisation NN cord-014597-66vd2mdu 1432 9 is be VBZ cord-014597-66vd2mdu 1432 10 hindered hinder VBN cord-014597-66vd2mdu 1432 11 ( ( -LRB- cord-014597-66vd2mdu 1432 12 Fig Fig NNP cord-014597-66vd2mdu 1432 13 . . . cord-014597-66vd2mdu 1432 14 1e 1e NNP cord-014597-66vd2mdu 1432 15 to to IN cord-014597-66vd2mdu 1432 16 h h NNP cord-014597-66vd2mdu 1432 17 ) ) -RRB- cord-014597-66vd2mdu 1432 18 . . . cord-014597-66vd2mdu 1433 1 -Add -add DT cord-014597-66vd2mdu 1433 2 growth growth NN cord-014597-66vd2mdu 1433 3 medium medium NN cord-014597-66vd2mdu 1433 4 , , , cord-014597-66vd2mdu 1433 5 and and CC cord-014597-66vd2mdu 1433 6 incubate incubate VB cord-014597-66vd2mdu 1433 7 plates plate NNS cord-014597-66vd2mdu 1433 8 . . . cord-014597-66vd2mdu 1434 1 Record record VB cord-014597-66vd2mdu 1434 2 all all DT cord-014597-66vd2mdu 1434 3 wells well NNS cord-014597-66vd2mdu 1434 4 containing contain VBG cord-014597-66vd2mdu 1434 5 colonies colony NNS cord-014597-66vd2mdu 1434 6 ; ; : cord-014597-66vd2mdu 1434 7 only only RB cord-014597-66vd2mdu 1434 8 progress progress NN cord-014597-66vd2mdu 1434 9 colonies colony NNS cord-014597-66vd2mdu 1434 10 from from IN cord-014597-66vd2mdu 1434 11 wells well NNS cord-014597-66vd2mdu 1434 12 that that WDT cord-014597-66vd2mdu 1434 13 both both DT cord-014597-66vd2mdu 1434 14 scientists scientist NNS cord-014597-66vd2mdu 1434 15 agree agree VBP cord-014597-66vd2mdu 1434 16 contains contain VBZ cord-014597-66vd2mdu 1434 17 only only RB cord-014597-66vd2mdu 1434 18 one one CD cord-014597-66vd2mdu 1434 19 cell cell NN cord-014597-66vd2mdu 1434 20 . . . cord-014597-66vd2mdu 1435 1 -Data -data NN cord-014597-66vd2mdu 1436 1 analysis analysis NN cord-014597-66vd2mdu 1436 2 : : : cord-014597-66vd2mdu 1437 1 -Each -Each . cord-014597-66vd2mdu 1438 1 scientist scientist NN cord-014597-66vd2mdu 1438 2 's 's POS cord-014597-66vd2mdu 1438 3 observations observation NNS cord-014597-66vd2mdu 1438 4 categorised categorise VBN cord-014597-66vd2mdu 1438 5 as as IN cord-014597-66vd2mdu 1438 6 : : : cord-014597-66vd2mdu 1438 7 0 0 CD cord-014597-66vd2mdu 1438 8 cells cell NNS cord-014597-66vd2mdu 1438 9 , , , cord-014597-66vd2mdu 1438 10 1 1 CD cord-014597-66vd2mdu 1438 11 cell cell NN cord-014597-66vd2mdu 1438 12 or or CC cord-014597-66vd2mdu 1438 13 > > NN cord-014597-66vd2mdu 1438 14 1 1 CD cord-014597-66vd2mdu 1438 15 cell cell NN cord-014597-66vd2mdu 1438 16 -Observed -observe VBD cord-014597-66vd2mdu 1438 17 outcome outcome NN cord-014597-66vd2mdu 1438 18 for for IN cord-014597-66vd2mdu 1438 19 each each DT cord-014597-66vd2mdu 1438 20 well well NN cord-014597-66vd2mdu 1438 21 : : : cord-014597-66vd2mdu 1438 22 growth growth NN cord-014597-66vd2mdu 1438 23 or or CC cord-014597-66vd2mdu 1438 24 no no DT cord-014597-66vd2mdu 1438 25 growth growth NN cord-014597-66vd2mdu 1438 26 -Probability -probability NN cord-014597-66vd2mdu 1438 27 of of IN cord-014597-66vd2mdu 1438 28 monoclonality monoclonality NN cord-014597-66vd2mdu 1438 29 estimated estimate VBN cord-014597-66vd2mdu 1438 30 from from IN cord-014597-66vd2mdu 1438 31 data datum NNS cord-014597-66vd2mdu 1438 32 using use VBG cord-014597-66vd2mdu 1438 33 a a DT cord-014597-66vd2mdu 1438 34 statistical statistical JJ cord-014597-66vd2mdu 1438 35 model model NN cord-014597-66vd2mdu 1438 36 Cloning clone VBG cord-014597-66vd2mdu 1438 37 ( ( -LRB- cord-014597-66vd2mdu 1438 38 LDC LDC NNP cord-014597-66vd2mdu 1438 39 ) ) -RRB- cord-014597-66vd2mdu 1439 1 Increased increased JJ cord-014597-66vd2mdu 1439 2 accuracy accuracy NN cord-014597-66vd2mdu 1439 3 of of IN cord-014597-66vd2mdu 1439 4 P(monoclonality P(monoclonality NNP cord-014597-66vd2mdu 1439 5 ) ) -RRB- cord-014597-66vd2mdu 1439 6 with with IN cord-014597-66vd2mdu 1439 7 CACC CACC NNP cord-014597-66vd2mdu 1439 8 -LDC -LDC JJS cord-014597-66vd2mdu 1439 9 weakness weakness NN cord-014597-66vd2mdu 1439 10 : : : cord-014597-66vd2mdu 1439 11 no no DT cord-014597-66vd2mdu 1439 12 visualisation visualisation NN cord-014597-66vd2mdu 1439 13 after after IN cord-014597-66vd2mdu 1439 14 seeding seed VBG cord-014597-66vd2mdu 1439 15 ( ( -LRB- cord-014597-66vd2mdu 1439 16 to to TO cord-014597-66vd2mdu 1439 17 check check VB cord-014597-66vd2mdu 1439 18 both both DT cord-014597-66vd2mdu 1439 19 well well RB cord-014597-66vd2mdu 1439 20 seeding seed VBG cord-014597-66vd2mdu 1439 21 and and CC cord-014597-66vd2mdu 1439 22 subsequent subsequent JJ cord-014597-66vd2mdu 1439 23 growth growth NN cord-014597-66vd2mdu 1439 24 of of IN cord-014597-66vd2mdu 1439 25 colonies colony NNS cord-014597-66vd2mdu 1439 26 is be VBZ cord-014597-66vd2mdu 1439 27 well well RB cord-014597-66vd2mdu 1439 28 described describe VBN cord-014597-66vd2mdu 1439 29 by by IN cord-014597-66vd2mdu 1439 30 the the DT cord-014597-66vd2mdu 1439 31 Poisson Poisson NNP cord-014597-66vd2mdu 1439 32 distribution distribution NN cord-014597-66vd2mdu 1439 33 ) ) -RRB- cord-014597-66vd2mdu 1439 34 , , , cord-014597-66vd2mdu 1439 35 potentially potentially RB cord-014597-66vd2mdu 1439 36 overestimating overestimate VBG cord-014597-66vd2mdu 1439 37 P(monoclonality p(monoclonality NN cord-014597-66vd2mdu 1439 38 ) ) -RRB- cord-014597-66vd2mdu 1440 1 -Addressed -addresse VBN cord-014597-66vd2mdu 1441 1 by by IN cord-014597-66vd2mdu 1441 2 CACC CACC NNP cord-014597-66vd2mdu 1441 3 : : : cord-014597-66vd2mdu 1441 4 Visual visual JJ cord-014597-66vd2mdu 1441 5 examination examination NN cord-014597-66vd2mdu 1441 6 with with IN cord-014597-66vd2mdu 1441 7 colonies colony NNS cord-014597-66vd2mdu 1441 8 arising arise VBG cord-014597-66vd2mdu 1441 9 from from IN cord-014597-66vd2mdu 1441 10 wells well NNS cord-014597-66vd2mdu 1441 11 seeded seed VBN cord-014597-66vd2mdu 1441 12 with with IN cord-014597-66vd2mdu 1441 13 1 1 CD cord-014597-66vd2mdu 1441 14 cell cell NN cord-014597-66vd2mdu 1441 15 distinguished distinguish VBN cord-014597-66vd2mdu 1441 16 from from IN cord-014597-66vd2mdu 1441 17 those those DT cord-014597-66vd2mdu 1441 18 seeded seed VBN cord-014597-66vd2mdu 1441 19 with with IN cord-014597-66vd2mdu 1441 20 > > XX cord-014597-66vd2mdu 1441 21 1 1 CD cord-014597-66vd2mdu 1441 22 cell cell NN cord-014597-66vd2mdu 1441 23 -Visualisation -visualisation NN cord-014597-66vd2mdu 1441 24 step step NN cord-014597-66vd2mdu 1441 25 further far RBR cord-014597-66vd2mdu 1441 26 strengthened strengthen VBN cord-014597-66vd2mdu 1441 27 by by IN cord-014597-66vd2mdu 1441 28 : : : cord-014597-66vd2mdu 1441 29 Using use VBG cord-014597-66vd2mdu 1441 30 controls control NNS cord-014597-66vd2mdu 1441 31 for for IN cord-014597-66vd2mdu 1441 32 exclusion exclusion NN cord-014597-66vd2mdu 1441 33 of of IN cord-014597-66vd2mdu 1441 34 wells well NNS cord-014597-66vd2mdu 1441 35 ; ; : cord-014597-66vd2mdu 1441 36 measuring measure VBG cord-014597-66vd2mdu 1441 37 errors error NNS cord-014597-66vd2mdu 1441 38 based base VBN cord-014597-66vd2mdu 1441 39 on on IN cord-014597-66vd2mdu 1441 40 the the DT cord-014597-66vd2mdu 1441 41 presence presence NN cord-014597-66vd2mdu 1441 42 or or CC cord-014597-66vd2mdu 1441 43 absence absence NN cord-014597-66vd2mdu 1441 44 of of IN cord-014597-66vd2mdu 1441 45 colonies colony NNS cord-014597-66vd2mdu 1441 46 in in IN cord-014597-66vd2mdu 1441 47 wells well NNS cord-014597-66vd2mdu 1441 48 where where WRB cord-014597-66vd2mdu 1441 49 two two CD cord-014597-66vd2mdu 1441 50 scientists scientist NNS cord-014597-66vd2mdu 1441 51 independently independently RB cord-014597-66vd2mdu 1441 52 reported report VBD cord-014597-66vd2mdu 1441 53 0 0 CD cord-014597-66vd2mdu 1441 54 cells cell NNS cord-014597-66vd2mdu 1441 55 ; ; : cord-014597-66vd2mdu 1441 56 and and CC cord-014597-66vd2mdu 1441 57 formally formally RB cord-014597-66vd2mdu 1441 58 analysing analyse VBG cord-014597-66vd2mdu 1441 59 the the DT cord-014597-66vd2mdu 1441 60 data datum NNS cord-014597-66vd2mdu 1441 61 using use VBG cord-014597-66vd2mdu 1441 62 a a DT cord-014597-66vd2mdu 1441 63 suitable suitable JJ cord-014597-66vd2mdu 1441 64 statistical statistical JJ cord-014597-66vd2mdu 1441 65 model model NN cord-014597-66vd2mdu 1441 66 Decreased decrease VBD cord-014597-66vd2mdu 1441 67 time time NN cord-014597-66vd2mdu 1441 68 and and CC cord-014597-66vd2mdu 1441 69 resource resource NN cord-014597-66vd2mdu 1441 70 requirements requirement NNS cord-014597-66vd2mdu 1441 71 with with IN cord-014597-66vd2mdu 1441 72 CACC CACC NNP cord-014597-66vd2mdu 1441 73 -High -High NNP cord-014597-66vd2mdu 1441 74 P(monoclonality P(monoclonality NNP cord-014597-66vd2mdu 1441 75 ) ) -RRB- cord-014597-66vd2mdu 1441 76 possible possible JJ cord-014597-66vd2mdu 1441 77 in in IN cord-014597-66vd2mdu 1441 78 single single JJ cord-014597-66vd2mdu 1441 79 round round NN cord-014597-66vd2mdu 1441 80 as as IN cord-014597-66vd2mdu 1441 81 each each DT cord-014597-66vd2mdu 1441 82 well well RB cord-014597-66vd2mdu 1441 83 examined examine VBN cord-014597-66vd2mdu 1441 84 individually individually RB cord-014597-66vd2mdu 1441 85 with with IN cord-014597-66vd2mdu 1441 86 only only RB cord-014597-66vd2mdu 1441 87 those those DT cord-014597-66vd2mdu 1441 88 containing contain VBG cord-014597-66vd2mdu 1441 89 a a DT cord-014597-66vd2mdu 1441 90 single single JJ cord-014597-66vd2mdu 1441 91 cell cell NN cord-014597-66vd2mdu 1441 92 progressed progress VBD cord-014597-66vd2mdu 1441 93 , , , cord-014597-66vd2mdu 1441 94 and and CC cord-014597-66vd2mdu 1442 1 because because IN cord-014597-66vd2mdu 1442 2 the the DT cord-014597-66vd2mdu 1442 3 error error NN cord-014597-66vd2mdu 1442 4 rate rate NN cord-014597-66vd2mdu 1442 5 for for IN cord-014597-66vd2mdu 1442 6 incorrect incorrect JJ cord-014597-66vd2mdu 1442 7 scoring scoring NN cord-014597-66vd2mdu 1442 8 is be VBZ cord-014597-66vd2mdu 1442 9 considered consider VBN cord-014597-66vd2mdu 1442 10 to to TO cord-014597-66vd2mdu 1442 11 be be VB cord-014597-66vd2mdu 1442 12 low low JJ cord-014597-66vd2mdu 1442 13 two two CD cord-014597-66vd2mdu 1442 14 scientists scientist NNS cord-014597-66vd2mdu 1442 15 miss miss VBP cord-014597-66vd2mdu 1442 16 a a DT cord-014597-66vd2mdu 1442 17 cell cell NN cord-014597-66vd2mdu 1442 18 one one CD cord-014597-66vd2mdu 1442 19 cell cell NN cord-014597-66vd2mdu 1442 20 sitting sit VBG cord-014597-66vd2mdu 1442 21 on on IN cord-014597-66vd2mdu 1442 22 top top NN cord-014597-66vd2mdu 1442 23 of of IN cord-014597-66vd2mdu 1442 24 another another DT cord-014597-66vd2mdu 1442 25 and and CC cord-014597-66vd2mdu 1442 26 the the DT cord-014597-66vd2mdu 1442 27 two two CD cord-014597-66vd2mdu 1442 28 thus thus RB cord-014597-66vd2mdu 1442 29 appearing appear VBG cord-014597-66vd2mdu 1442 30 as as IN cord-014597-66vd2mdu 1442 31 one one CD cord-014597-66vd2mdu 1442 32 An an DT cord-014597-66vd2mdu 1442 33 experiment experiment NN cord-014597-66vd2mdu 1442 34 was be VBD cord-014597-66vd2mdu 1442 35 performed perform VBN cord-014597-66vd2mdu 1442 36 to to TO cord-014597-66vd2mdu 1442 37 estimate estimate VB cord-014597-66vd2mdu 1442 38 error error NN cord-014597-66vd2mdu 1442 39 frequency frequency NN cord-014597-66vd2mdu 1442 40 [ [ -LRB- cord-014597-66vd2mdu 1442 41 3 3 CD cord-014597-66vd2mdu 1442 42 ] ] -RRB- cord-014597-66vd2mdu 1442 43 . . . cord-014597-66vd2mdu 1443 1 Conclusion conclusion NN cord-014597-66vd2mdu 1443 2 -Scientists -scientist NNS cord-014597-66vd2mdu 1443 3 miss miss VB cord-014597-66vd2mdu 1443 4 a a DT cord-014597-66vd2mdu 1443 5 cell cell NN cord-014597-66vd2mdu 1443 6 infrequently infrequently RB cord-014597-66vd2mdu 1443 7 ( ( -LRB- cord-014597-66vd2mdu 1443 8 in in IN cord-014597-66vd2mdu 1443 9 the the DT cord-014597-66vd2mdu 1443 10 range range NN cord-014597-66vd2mdu 1443 11 0.4 0.4 CD cord-014597-66vd2mdu 1443 12 % % NN cord-014597-66vd2mdu 1443 13 to to IN cord-014597-66vd2mdu 1443 14 1.3 1.3 CD cord-014597-66vd2mdu 1443 15 % % NN cord-014597-66vd2mdu 1443 16 , , , cord-014597-66vd2mdu 1443 17 [ [ -LRB- cord-014597-66vd2mdu 1443 18 3 3 CD cord-014597-66vd2mdu 1443 19 ] ] -RRB- cord-014597-66vd2mdu 1443 20 ) ) -RRB- cord-014597-66vd2mdu 1444 1 -Error -Error : cord-014597-66vd2mdu 1444 2 frequency frequency NN cord-014597-66vd2mdu 1444 3 does do VBZ cord-014597-66vd2mdu 1444 4 not not RB cord-014597-66vd2mdu 1444 5 invalidate invalidate VB cord-014597-66vd2mdu 1444 6 use use NN cord-014597-66vd2mdu 1444 7 of of IN cord-014597-66vd2mdu 1444 8 direct direct JJ cord-014597-66vd2mdu 1444 9 observation observation NN cord-014597-66vd2mdu 1444 10 methods method NNS cord-014597-66vd2mdu 1444 11 for for IN cord-014597-66vd2mdu 1444 12 cell cell NN cord-014597-66vd2mdu 1444 13 cloning cloning NN cord-014597-66vd2mdu 1444 14 -Single -single IN cord-014597-66vd2mdu 1444 15 cell cell NN cord-014597-66vd2mdu 1444 16 seen see VBN cord-014597-66vd2mdu 1444 17 by by IN cord-014597-66vd2mdu 1444 18 both both DT cord-014597-66vd2mdu 1444 19 scientists scientist NNS cord-014597-66vd2mdu 1444 20 is be VBZ cord-014597-66vd2mdu 1444 21 highly highly RB cord-014597-66vd2mdu 1444 22 likely likely JJ cord-014597-66vd2mdu 1444 23 to to TO cord-014597-66vd2mdu 1444 24 be be VB cord-014597-66vd2mdu 1444 25 monoclonal monoclonal JJ cord-014597-66vd2mdu 1444 26 -During -during NN cord-014597-66vd2mdu 1444 27 method method NN cord-014597-66vd2mdu 1444 28 development development NN cord-014597-66vd2mdu 1444 29 , , , cord-014597-66vd2mdu 1444 30 strategies strategy NNS cord-014597-66vd2mdu 1444 31 established establish VBN cord-014597-66vd2mdu 1444 32 to to TO cord-014597-66vd2mdu 1444 33 control control VB cord-014597-66vd2mdu 1444 34 potential potential JJ cord-014597-66vd2mdu 1444 35 sources source NNS cord-014597-66vd2mdu 1444 36 of of IN cord-014597-66vd2mdu 1444 37 error error NN cord-014597-66vd2mdu 1444 38 ( ( -LRB- cord-014597-66vd2mdu 1444 39 Table table NN cord-014597-66vd2mdu 1444 40 1 1 CD cord-014597-66vd2mdu 1444 41 ) ) -RRB- cord-014597-66vd2mdu 1444 42 Use use NN cord-014597-66vd2mdu 1444 43 of of IN cord-014597-66vd2mdu 1444 44 a a DT cord-014597-66vd2mdu 1444 45 contemporaneous contemporaneous JJ cord-014597-66vd2mdu 1444 46 visualisation visualisation NN cord-014597-66vd2mdu 1444 47 approach approach NN cord-014597-66vd2mdu 1444 48 , , , cord-014597-66vd2mdu 1444 49 a a DT cord-014597-66vd2mdu 1444 50 strict strict JJ cord-014597-66vd2mdu 1444 51 control control NN cord-014597-66vd2mdu 1444 52 strategy strategy NN cord-014597-66vd2mdu 1444 53 , , , cord-014597-66vd2mdu 1444 54 and and CC cord-014597-66vd2mdu 1444 55 a a DT cord-014597-66vd2mdu 1444 56 suitable suitable JJ cord-014597-66vd2mdu 1444 57 statistical statistical JJ cord-014597-66vd2mdu 1444 58 model model NN cord-014597-66vd2mdu 1444 59 ( ( -LRB- cord-014597-66vd2mdu 1444 60 which which WDT cord-014597-66vd2mdu 1444 61 takes take VBZ cord-014597-66vd2mdu 1444 62 into into IN cord-014597-66vd2mdu 1444 63 account account NN cord-014597-66vd2mdu 1444 64 potential potential JJ cord-014597-66vd2mdu 1444 65 errors error NNS cord-014597-66vd2mdu 1444 66 ) ) -RRB- cord-014597-66vd2mdu 1444 67 results result VBZ cord-014597-66vd2mdu 1444 68 in in IN cord-014597-66vd2mdu 1444 69 : : : cord-014597-66vd2mdu 1444 70 -The -The : cord-014597-66vd2mdu 1444 71 CACC CACC NNP cord-014597-66vd2mdu 1444 72 method method NN cord-014597-66vd2mdu 1444 73 being be VBG cord-014597-66vd2mdu 1444 74 at at RB cord-014597-66vd2mdu 1444 75 least least JJS cord-014597-66vd2mdu 1444 76 as as RB cord-014597-66vd2mdu 1444 77 robust robust JJ cord-014597-66vd2mdu 1444 78 as as IN cord-014597-66vd2mdu 1444 79 the the DT cord-014597-66vd2mdu 1444 80 LDC LDC NNP cord-014597-66vd2mdu 1444 81 method method NN cord-014597-66vd2mdu 1444 82 -The -The : cord-014597-66vd2mdu 1444 83 CACC CACC NNP cord-014597-66vd2mdu 1444 84 method method NN cord-014597-66vd2mdu 1444 85 being be VBG cord-014597-66vd2mdu 1444 86 a a DT cord-014597-66vd2mdu 1444 87 reliable reliable JJ cord-014597-66vd2mdu 1444 88 , , , cord-014597-66vd2mdu 1444 89 single single JJ cord-014597-66vd2mdu 1444 90 - - HYPH cord-014597-66vd2mdu 1444 91 step step NN cord-014597-66vd2mdu 1444 92 method method NN cord-014597-66vd2mdu 1444 93 for for IN cord-014597-66vd2mdu 1444 94 cloning clone VBG cord-014597-66vd2mdu 1444 95 to to TO cord-014597-66vd2mdu 1444 96 achieve achieve VB cord-014597-66vd2mdu 1444 97 a a DT cord-014597-66vd2mdu 1444 98 high high JJ cord-014597-66vd2mdu 1444 99 P(monoclonality p(monoclonality NN cord-014597-66vd2mdu 1444 100 ) ) -RRB- cord-014597-66vd2mdu 1445 1 Background background NN cord-014597-66vd2mdu 1445 2 Vector Vector NNP cord-014597-66vd2mdu 1445 3 design design NN cord-014597-66vd2mdu 1445 4 is be VBZ cord-014597-66vd2mdu 1445 5 a a DT cord-014597-66vd2mdu 1445 6 key key JJ cord-014597-66vd2mdu 1445 7 step step NN cord-014597-66vd2mdu 1445 8 in in IN cord-014597-66vd2mdu 1445 9 cell cell NN cord-014597-66vd2mdu 1445 10 line line NN cord-014597-66vd2mdu 1445 11 development development NN cord-014597-66vd2mdu 1445 12 for for IN cord-014597-66vd2mdu 1445 13 the the DT cord-014597-66vd2mdu 1445 14 expression expression NN cord-014597-66vd2mdu 1445 15 of of IN cord-014597-66vd2mdu 1445 16 therapeutic therapeutic JJ cord-014597-66vd2mdu 1445 17 biologics biologic NNS cord-014597-66vd2mdu 1445 18 . . . cord-014597-66vd2mdu 1446 1 It -PRON- PRP cord-014597-66vd2mdu 1446 2 is be VBZ cord-014597-66vd2mdu 1446 3 essential essential JJ cord-014597-66vd2mdu 1446 4 that that IN cord-014597-66vd2mdu 1446 5 the the DT cord-014597-66vd2mdu 1446 6 vector vector NN cord-014597-66vd2mdu 1446 7 design design NN cord-014597-66vd2mdu 1446 8 results result NNS cord-014597-66vd2mdu 1446 9 in in IN cord-014597-66vd2mdu 1446 10 high high JJ cord-014597-66vd2mdu 1446 11 , , , cord-014597-66vd2mdu 1446 12 stable stable JJ cord-014597-66vd2mdu 1446 13 expression expression NN cord-014597-66vd2mdu 1446 14 of of IN cord-014597-66vd2mdu 1446 15 the the DT cord-014597-66vd2mdu 1446 16 encoded encode VBN cord-014597-66vd2mdu 1446 17 protein protein NN cord-014597-66vd2mdu 1446 18 . . . cord-014597-66vd2mdu 1447 1 Other other JJ cord-014597-66vd2mdu 1447 2 considerations consideration NNS cord-014597-66vd2mdu 1447 3 include include VBP cord-014597-66vd2mdu 1447 4 ease ease NN cord-014597-66vd2mdu 1447 5 of of IN cord-014597-66vd2mdu 1447 6 cloning cloning NN cord-014597-66vd2mdu 1447 7 , , , cord-014597-66vd2mdu 1447 8 stability stability NN cord-014597-66vd2mdu 1447 9 for for IN cord-014597-66vd2mdu 1447 10 propagation propagation NN cord-014597-66vd2mdu 1447 11 in in IN cord-014597-66vd2mdu 1447 12 E. E. NNP cord-014597-66vd2mdu 1447 13 coli coli NNS cord-014597-66vd2mdu 1447 14 as as RB cord-014597-66vd2mdu 1447 15 well well RB cord-014597-66vd2mdu 1447 16 as as IN cord-014597-66vd2mdu 1447 17 in in IN cord-014597-66vd2mdu 1447 18 the the DT cord-014597-66vd2mdu 1447 19 mammalian mammalian JJ cord-014597-66vd2mdu 1447 20 host host NN cord-014597-66vd2mdu 1447 21 cell cell NN cord-014597-66vd2mdu 1447 22 line line NN cord-014597-66vd2mdu 1447 23 , , , cord-014597-66vd2mdu 1447 24 and and CC cord-014597-66vd2mdu 1447 25 ease ease NN cord-014597-66vd2mdu 1447 26 of of IN cord-014597-66vd2mdu 1447 27 sequence sequence NN cord-014597-66vd2mdu 1447 28 amplification amplification NN cord-014597-66vd2mdu 1447 29 for for IN cord-014597-66vd2mdu 1447 30 verification verification NN cord-014597-66vd2mdu 1447 31 of of IN cord-014597-66vd2mdu 1447 32 vector vector NN cord-014597-66vd2mdu 1447 33 construction construction NN cord-014597-66vd2mdu 1447 34 and and CC cord-014597-66vd2mdu 1447 35 for for IN cord-014597-66vd2mdu 1447 36 detection detection NN cord-014597-66vd2mdu 1447 37 of of IN cord-014597-66vd2mdu 1447 38 insertion insertion NN cord-014597-66vd2mdu 1447 39 site site NN cord-014597-66vd2mdu 1447 40 and and CC cord-014597-66vd2mdu 1447 41 copy copy NN cord-014597-66vd2mdu 1447 42 number number NN cord-014597-66vd2mdu 1447 43 in in IN cord-014597-66vd2mdu 1447 44 stably stably RB cord-014597-66vd2mdu 1447 45 expressing express VBG cord-014597-66vd2mdu 1447 46 cells cell NNS cord-014597-66vd2mdu 1447 47 . . . cord-014597-66vd2mdu 1448 1 For for IN cord-014597-66vd2mdu 1448 2 these these DT cord-014597-66vd2mdu 1448 3 reasons reason NNS cord-014597-66vd2mdu 1448 4 , , , cord-014597-66vd2mdu 1448 5 use use NN cord-014597-66vd2mdu 1448 6 of of IN cord-014597-66vd2mdu 1448 7 the the DT cord-014597-66vd2mdu 1448 8 same same JJ cord-014597-66vd2mdu 1448 9 promoters promoter NNS cord-014597-66vd2mdu 1448 10 and and CC cord-014597-66vd2mdu 1448 11 polyA polyA NNP cord-014597-66vd2mdu 1448 12 tails tail NNS cord-014597-66vd2mdu 1448 13 in in IN cord-014597-66vd2mdu 1448 14 dual dual JJ cord-014597-66vd2mdu 1448 15 cassette cassette NN cord-014597-66vd2mdu 1448 16 vectors vector NNS cord-014597-66vd2mdu 1448 17 , , , cord-014597-66vd2mdu 1448 18 as as IN cord-014597-66vd2mdu 1448 19 is be VBZ cord-014597-66vd2mdu 1448 20 common common JJ cord-014597-66vd2mdu 1448 21 for for IN cord-014597-66vd2mdu 1448 22 expression expression NN cord-014597-66vd2mdu 1448 23 of of IN cord-014597-66vd2mdu 1448 24 the the DT cord-014597-66vd2mdu 1448 25 heavy heavy JJ cord-014597-66vd2mdu 1448 26 and and CC cord-014597-66vd2mdu 1448 27 light light JJ cord-014597-66vd2mdu 1448 28 chains chain NNS cord-014597-66vd2mdu 1448 29 of of IN cord-014597-66vd2mdu 1448 30 monoclonal monoclonal JJ cord-014597-66vd2mdu 1448 31 antibodies antibody NNS cord-014597-66vd2mdu 1448 32 , , , cord-014597-66vd2mdu 1448 33 can can MD cord-014597-66vd2mdu 1448 34 be be VB cord-014597-66vd2mdu 1448 35 problematic problematic JJ cord-014597-66vd2mdu 1448 36 . . . cord-014597-66vd2mdu 1449 1 In in IN cord-014597-66vd2mdu 1449 2 order order NN cord-014597-66vd2mdu 1449 3 to to TO cord-014597-66vd2mdu 1449 4 minimize minimize VB cord-014597-66vd2mdu 1449 5 sequence sequence NN cord-014597-66vd2mdu 1449 6 similarities similarity NNS cord-014597-66vd2mdu 1449 7 between between IN cord-014597-66vd2mdu 1449 8 the the DT cord-014597-66vd2mdu 1449 9 two two CD cord-014597-66vd2mdu 1449 10 expression expression NN cord-014597-66vd2mdu 1449 11 cassettes cassette NNS cord-014597-66vd2mdu 1449 12 , , , cord-014597-66vd2mdu 1449 13 we -PRON- PRP cord-014597-66vd2mdu 1449 14 have have VBP cord-014597-66vd2mdu 1449 15 modified modify VBN cord-014597-66vd2mdu 1449 16 the the DT cord-014597-66vd2mdu 1449 17 promoters promoter NNS cord-014597-66vd2mdu 1449 18 , , , cord-014597-66vd2mdu 1449 19 introns intron NNS cord-014597-66vd2mdu 1449 20 , , , cord-014597-66vd2mdu 1449 21 and and CC cord-014597-66vd2mdu 1449 22 polyA polyA NNP cord-014597-66vd2mdu 1449 23 tails tail NNS cord-014597-66vd2mdu 1449 24 of of IN cord-014597-66vd2mdu 1449 25 the the DT cord-014597-66vd2mdu 1449 26 light light JJ cord-014597-66vd2mdu 1449 27 chain chain NN cord-014597-66vd2mdu 1449 28 and and CC cord-014597-66vd2mdu 1449 29 heavy heavy JJ cord-014597-66vd2mdu 1449 30 chain chain NN cord-014597-66vd2mdu 1449 31 expression expression NN cord-014597-66vd2mdu 1449 32 cassettes cassette NNS cord-014597-66vd2mdu 1449 33 in in IN cord-014597-66vd2mdu 1449 34 the the DT cord-014597-66vd2mdu 1449 35 dual dual JJ cord-014597-66vd2mdu 1449 36 expression expression NN cord-014597-66vd2mdu 1449 37 vector vector NN cord-014597-66vd2mdu 1449 38 commonly commonly RB cord-014597-66vd2mdu 1449 39 used use VBN cord-014597-66vd2mdu 1449 40 for for IN cord-014597-66vd2mdu 1449 41 the the DT cord-014597-66vd2mdu 1449 42 expression expression NN cord-014597-66vd2mdu 1449 43 of of IN cord-014597-66vd2mdu 1449 44 therapeutic therapeutic JJ cord-014597-66vd2mdu 1449 45 antibodies antibody NNS cord-014597-66vd2mdu 1449 46 in in IN cord-014597-66vd2mdu 1449 47 the the DT cord-014597-66vd2mdu 1449 48 CHOZN CHOZN NNP cord-014597-66vd2mdu 1449 49 ® ® NNPS cord-014597-66vd2mdu 1449 50 GS GS NNP cord-014597-66vd2mdu 1449 51 -/cell -/cell NNP cord-014597-66vd2mdu 1449 52 line line NNP cord-014597-66vd2mdu 1449 53 development development NN cord-014597-66vd2mdu 1449 54 platform platform NN cord-014597-66vd2mdu 1449 55 . . . cord-014597-66vd2mdu 1450 1 Gene gene NN cord-014597-66vd2mdu 1450 2 synthesis synthesis NN cord-014597-66vd2mdu 1450 3 and and CC cord-014597-66vd2mdu 1450 4 vector vector NN cord-014597-66vd2mdu 1450 5 construction construction NN cord-014597-66vd2mdu 1450 6 of of IN cord-014597-66vd2mdu 1450 7 IgG1 igg1 NN cord-014597-66vd2mdu 1450 8 and and CC cord-014597-66vd2mdu 1450 9 fluorophore fluorophore NN cord-014597-66vd2mdu 1450 10 - - HYPH cord-014597-66vd2mdu 1450 11 expressing express VBG cord-014597-66vd2mdu 1450 12 vectors vector NNS cord-014597-66vd2mdu 1450 13 was be VBD cord-014597-66vd2mdu 1450 14 done do VBN cord-014597-66vd2mdu 1450 15 by by IN cord-014597-66vd2mdu 1450 16 Atum Atum NNP cord-014597-66vd2mdu 1450 17 . . . cord-014597-66vd2mdu 1451 1 Vectors vector NNS cord-014597-66vd2mdu 1451 2 were be VBD cord-014597-66vd2mdu 1451 3 transfected transfecte VBN cord-014597-66vd2mdu 1451 4 into into IN cord-014597-66vd2mdu 1451 5 CHOZN CHOZN NNP cord-014597-66vd2mdu 1451 6 ® ® POS cord-014597-66vd2mdu 1451 7 GS GS NNP cord-014597-66vd2mdu 1451 8 -/cells -/cell VBZ cord-014597-66vd2mdu 1451 9 via via IN cord-014597-66vd2mdu 1451 10 electroporation electroporation NN cord-014597-66vd2mdu 1451 11 . . . cord-014597-66vd2mdu 1452 1 Analysis Analysis NNP cord-014597-66vd2mdu 1452 2 of of IN cord-014597-66vd2mdu 1452 3 GFP GFP NNP cord-014597-66vd2mdu 1452 4 and and CC cord-014597-66vd2mdu 1452 5 RFP RFP NNP cord-014597-66vd2mdu 1452 6 expression expression NN cord-014597-66vd2mdu 1452 7 was be VBD cord-014597-66vd2mdu 1452 8 achieved achieve VBN cord-014597-66vd2mdu 1452 9 using use VBG cord-014597-66vd2mdu 1452 10 a a DT cord-014597-66vd2mdu 1452 11 MACSQuant macsquant NN cord-014597-66vd2mdu 1452 12 instrument instrument NN cord-014597-66vd2mdu 1452 13 . . . cord-014597-66vd2mdu 1453 1 Selection selection NN cord-014597-66vd2mdu 1453 2 and and CC cord-014597-66vd2mdu 1453 3 generation generation NN cord-014597-66vd2mdu 1453 4 of of IN cord-014597-66vd2mdu 1453 5 stable stable JJ cord-014597-66vd2mdu 1453 6 pools pool NNS cord-014597-66vd2mdu 1453 7 and and CC cord-014597-66vd2mdu 1453 8 single single JJ cord-014597-66vd2mdu 1453 9 cell cell NN cord-014597-66vd2mdu 1453 10 clones clone NNS cord-014597-66vd2mdu 1453 11 from from IN cord-014597-66vd2mdu 1453 12 transfections transfection NNS cord-014597-66vd2mdu 1453 13 with with IN cord-014597-66vd2mdu 1453 14 IgG1-encoding igg1-encoding NN cord-014597-66vd2mdu 1453 15 vectors vector NNS cord-014597-66vd2mdu 1453 16 was be VBD cord-014597-66vd2mdu 1453 17 performed perform VBN cord-014597-66vd2mdu 1453 18 as as IN cord-014597-66vd2mdu 1453 19 described describe VBN cord-014597-66vd2mdu 1453 20 in in IN cord-014597-66vd2mdu 1453 21 the the DT cord-014597-66vd2mdu 1453 22 CHOZN CHOZN NNP cord-014597-66vd2mdu 1453 23 ® ® NNP cord-014597-66vd2mdu 1453 24 Platform Platform NNP cord-014597-66vd2mdu 1453 25 Technical Technical NNP cord-014597-66vd2mdu 1453 26 Bulletin Bulletin NNP cord-014597-66vd2mdu 1453 27 . . . cord-014597-66vd2mdu 1454 1 Titer titer NN cord-014597-66vd2mdu 1454 2 analysis analysis NN cord-014597-66vd2mdu 1454 3 was be VBD cord-014597-66vd2mdu 1454 4 performed perform VBN cord-014597-66vd2mdu 1454 5 in in IN cord-014597-66vd2mdu 1454 6 static static JJ cord-014597-66vd2mdu 1454 7 ( ( -LRB- cord-014597-66vd2mdu 1454 8 96 96 CD cord-014597-66vd2mdu 1454 9 well well NN cord-014597-66vd2mdu 1454 10 plate plate NN cord-014597-66vd2mdu 1454 11 ) ) -RRB- cord-014597-66vd2mdu 1454 12 , , , cord-014597-66vd2mdu 1454 13 in in IN cord-014597-66vd2mdu 1454 14 a a DT cord-014597-66vd2mdu 1454 15 7 7 CD cord-014597-66vd2mdu 1454 16 day day NN cord-014597-66vd2mdu 1454 17 TPP tpp NN cord-014597-66vd2mdu 1454 18 assay assay NN cord-014597-66vd2mdu 1454 19 and and CC cord-014597-66vd2mdu 1454 20 in in IN cord-014597-66vd2mdu 1454 21 a a DT cord-014597-66vd2mdu 1454 22 14 14 CD cord-014597-66vd2mdu 1454 23 day day NN cord-014597-66vd2mdu 1454 24 fed feed VBN cord-014597-66vd2mdu 1454 25 batch batch NN cord-014597-66vd2mdu 1454 26 assay assay NN cord-014597-66vd2mdu 1454 27 using use VBG cord-014597-66vd2mdu 1454 28 a a DT cord-014597-66vd2mdu 1454 29 QK QK NNP cord-014597-66vd2mdu 1454 30 ForteBio ForteBio NNP cord-014597-66vd2mdu 1454 31 . . . cord-014597-66vd2mdu 1455 1 Initial initial JJ cord-014597-66vd2mdu 1455 2 screening screening NN cord-014597-66vd2mdu 1455 3 experiments experiment NNS cord-014597-66vd2mdu 1455 4 identified identify VBD cord-014597-66vd2mdu 1455 5 a a DT cord-014597-66vd2mdu 1455 6 lead lead JJ cord-014597-66vd2mdu 1455 7 vector vector NN cord-014597-66vd2mdu 1455 8 , , , cord-014597-66vd2mdu 1455 9 # # $ cord-014597-66vd2mdu 1455 10 39 39 CD cord-014597-66vd2mdu 1455 11 , , , cord-014597-66vd2mdu 1455 12 and and CC cord-014597-66vd2mdu 1455 13 a a DT cord-014597-66vd2mdu 1455 14 vector vector NN cord-014597-66vd2mdu 1455 15 , , , cord-014597-66vd2mdu 1455 16 # # $ cord-014597-66vd2mdu 1455 17 37 37 CD cord-014597-66vd2mdu 1455 18 , , , cord-014597-66vd2mdu 1455 19 which which WDT cord-014597-66vd2mdu 1455 20 produced produce VBD cord-014597-66vd2mdu 1455 21 very very RB cord-014597-66vd2mdu 1455 22 low low JJ cord-014597-66vd2mdu 1455 23 titers titer NNS cord-014597-66vd2mdu 1455 24 and and CC cord-014597-66vd2mdu 1455 25 relatively relatively RB cord-014597-66vd2mdu 1455 26 few few JJ cord-014597-66vd2mdu 1455 27 minipools minipool NNS cord-014597-66vd2mdu 1455 28 expressing express VBG cord-014597-66vd2mdu 1455 29 detectable detectable JJ cord-014597-66vd2mdu 1455 30 levels level NNS cord-014597-66vd2mdu 1455 31 of of IN cord-014597-66vd2mdu 1455 32 IgG1 igg1 NN cord-014597-66vd2mdu 1455 33 . . . cord-014597-66vd2mdu 1456 1 Analysis Analysis NNP cord-014597-66vd2mdu 1456 2 of of IN cord-014597-66vd2mdu 1456 3 GFP GFP NNP cord-014597-66vd2mdu 1456 4 and and CC cord-014597-66vd2mdu 1456 5 RFP RFP NNP cord-014597-66vd2mdu 1456 6 expression expression NN cord-014597-66vd2mdu 1456 7 from from IN cord-014597-66vd2mdu 1456 8 the the DT cord-014597-66vd2mdu 1456 9 modified modify VBN cord-014597-66vd2mdu 1456 10 vectors vector NNS cord-014597-66vd2mdu 1456 11 indicated indicate VBD cord-014597-66vd2mdu 1456 12 relatively relatively RB cord-014597-66vd2mdu 1456 13 high high JJ cord-014597-66vd2mdu 1456 14 expression expression NN cord-014597-66vd2mdu 1456 15 from from IN cord-014597-66vd2mdu 1456 16 the the DT cord-014597-66vd2mdu 1456 17 RFP RFP NNP cord-014597-66vd2mdu 1456 18 / / SYM cord-014597-66vd2mdu 1456 19 HC HC NNP cord-014597-66vd2mdu 1456 20 expression expression NN cord-014597-66vd2mdu 1456 21 cassette cassette NN cord-014597-66vd2mdu 1456 22 of of IN cord-014597-66vd2mdu 1456 23 vector vector NN cord-014597-66vd2mdu 1456 24 # # $ cord-014597-66vd2mdu 1456 25 37 37 CD cord-014597-66vd2mdu 1456 26 . . . cord-014597-66vd2mdu 1457 1 A a DT cord-014597-66vd2mdu 1457 2 stronger strong JJR cord-014597-66vd2mdu 1457 3 promoter promoter NN cord-014597-66vd2mdu 1457 4 resulting result VBG cord-014597-66vd2mdu 1457 5 in in IN cord-014597-66vd2mdu 1457 6 overabundance overabundance NN cord-014597-66vd2mdu 1457 7 of of IN cord-014597-66vd2mdu 1457 8 HC HC NNP cord-014597-66vd2mdu 1457 9 , , , cord-014597-66vd2mdu 1457 10 known know VBN cord-014597-66vd2mdu 1457 11 to to TO cord-014597-66vd2mdu 1457 12 be be VB cord-014597-66vd2mdu 1457 13 toxic toxic JJ cord-014597-66vd2mdu 1457 14 to to IN cord-014597-66vd2mdu 1457 15 cells cell NNS cord-014597-66vd2mdu 1457 16 , , , cord-014597-66vd2mdu 1457 17 provides provide VBZ cord-014597-66vd2mdu 1457 18 a a DT cord-014597-66vd2mdu 1457 19 possible possible JJ cord-014597-66vd2mdu 1457 20 explanation explanation NN cord-014597-66vd2mdu 1457 21 for for IN cord-014597-66vd2mdu 1457 22 the the DT cord-014597-66vd2mdu 1457 23 poor poor JJ cord-014597-66vd2mdu 1457 24 results result NNS cord-014597-66vd2mdu 1457 25 with with IN cord-014597-66vd2mdu 1457 26 this this DT cord-014597-66vd2mdu 1457 27 vector vector NN cord-014597-66vd2mdu 1457 28 . . . cord-014597-66vd2mdu 1458 1 Interestingly interestingly RB cord-014597-66vd2mdu 1458 2 , , , cord-014597-66vd2mdu 1458 3 swapping swap VBG cord-014597-66vd2mdu 1458 4 the the DT cord-014597-66vd2mdu 1458 5 positions position NNS cord-014597-66vd2mdu 1458 6 of of IN cord-014597-66vd2mdu 1458 7 the the DT cord-014597-66vd2mdu 1458 8 LC LC NNP cord-014597-66vd2mdu 1458 9 and and CC cord-014597-66vd2mdu 1458 10 HC HC NNP cord-014597-66vd2mdu 1458 11 in in IN cord-014597-66vd2mdu 1458 12 # # $ cord-014597-66vd2mdu 1458 13 37 37 CD cord-014597-66vd2mdu 1458 14 resulted result VBD cord-014597-66vd2mdu 1458 15 in in IN cord-014597-66vd2mdu 1458 16 a a DT cord-014597-66vd2mdu 1458 17 vector vector NN cord-014597-66vd2mdu 1458 18 , , , cord-014597-66vd2mdu 1458 19 # # $ cord-014597-66vd2mdu 1458 20 77 77 CD cord-014597-66vd2mdu 1458 21 , , , cord-014597-66vd2mdu 1458 22 that that WDT cord-014597-66vd2mdu 1458 23 outperformed outperform VBD cord-014597-66vd2mdu 1458 24 the the DT cord-014597-66vd2mdu 1458 25 initially initially RB cord-014597-66vd2mdu 1458 26 identified identify VBN cord-014597-66vd2mdu 1458 27 lead lead JJ cord-014597-66vd2mdu 1458 28 vector vector NN cord-014597-66vd2mdu 1458 29 ( ( -LRB- cord-014597-66vd2mdu 1458 30 Fig fig NN cord-014597-66vd2mdu 1458 31 . . . cord-014597-66vd2mdu 1458 32 1 1 CD cord-014597-66vd2mdu 1458 33 ) ) -RRB- cord-014597-66vd2mdu 1458 34 . . . cord-014597-66vd2mdu 1459 1 This this DT cord-014597-66vd2mdu 1459 2 same same JJ cord-014597-66vd2mdu 1459 3 change change NN cord-014597-66vd2mdu 1459 4 was be VBD cord-014597-66vd2mdu 1459 5 made make VBN cord-014597-66vd2mdu 1459 6 to to TO cord-014597-66vd2mdu 1459 7 vector vector VB cord-014597-66vd2mdu 1459 8 # # $ cord-014597-66vd2mdu 1459 9 39 39 CD cord-014597-66vd2mdu 1459 10 without without IN cord-014597-66vd2mdu 1459 11 any any DT cord-014597-66vd2mdu 1459 12 resulting result VBG cord-014597-66vd2mdu 1459 13 improvement improvement NN cord-014597-66vd2mdu 1459 14 in in IN cord-014597-66vd2mdu 1459 15 titers titer NNS cord-014597-66vd2mdu 1459 16 ( ( -LRB- cord-014597-66vd2mdu 1459 17 vector vector NN cord-014597-66vd2mdu 1459 18 # # $ cord-014597-66vd2mdu 1459 19 78 78 CD cord-014597-66vd2mdu 1459 20 , , , cord-014597-66vd2mdu 1459 21 Fig Fig NNP cord-014597-66vd2mdu 1459 22 . . NNP cord-014597-66vd2mdu 1459 23 1 1 CD cord-014597-66vd2mdu 1459 24 ) ) -RRB- cord-014597-66vd2mdu 1459 25 . . . cord-014597-66vd2mdu 1460 1 Interestingly interestingly RB cord-014597-66vd2mdu 1460 2 , , , cord-014597-66vd2mdu 1460 3 vector vector NN cord-014597-66vd2mdu 1460 4 # # $ cord-014597-66vd2mdu 1460 5 39 39 CD cord-014597-66vd2mdu 1460 6 had have VBD cord-014597-66vd2mdu 1460 7 a a DT cord-014597-66vd2mdu 1460 8 smaller small JJR cord-014597-66vd2mdu 1460 9 difference difference NN cord-014597-66vd2mdu 1460 10 in in IN cord-014597-66vd2mdu 1460 11 relative relative JJ cord-014597-66vd2mdu 1460 12 promoter promoter NN cord-014597-66vd2mdu 1460 13 strengths strength NNS cord-014597-66vd2mdu 1460 14 , , , cord-014597-66vd2mdu 1460 15 based base VBN cord-014597-66vd2mdu 1460 16 on on IN cord-014597-66vd2mdu 1460 17 mean mean JJ cord-014597-66vd2mdu 1460 18 channel channel NN cord-014597-66vd2mdu 1460 19 fluorescence fluorescence NN cord-014597-66vd2mdu 1460 20 ratio ratio NN cord-014597-66vd2mdu 1460 21 of of IN cord-014597-66vd2mdu 1460 22 GFP GFP NNP cord-014597-66vd2mdu 1460 23 to to IN cord-014597-66vd2mdu 1460 24 RFP RFP NNP cord-014597-66vd2mdu 1460 25 , , , cord-014597-66vd2mdu 1460 26 suggesting suggest VBG cord-014597-66vd2mdu 1460 27 that that IN cord-014597-66vd2mdu 1460 28 overabundance overabundance NN cord-014597-66vd2mdu 1460 29 of of IN cord-014597-66vd2mdu 1460 30 HC HC NNP cord-014597-66vd2mdu 1460 31 was be VBD cord-014597-66vd2mdu 1460 32 not not RB cord-014597-66vd2mdu 1460 33 an an DT cord-014597-66vd2mdu 1460 34 impediment impediment NN cord-014597-66vd2mdu 1460 35 to to IN cord-014597-66vd2mdu 1460 36 IgG1 igg1 CD cord-014597-66vd2mdu 1460 37 expression expression NN cord-014597-66vd2mdu 1460 38 from from IN cord-014597-66vd2mdu 1460 39 # # $ cord-014597-66vd2mdu 1460 40 39 39 CD cord-014597-66vd2mdu 1460 41 . . . cord-014597-66vd2mdu 1461 1 Poor poor JJ cord-014597-66vd2mdu 1461 2 titers titer NNS cord-014597-66vd2mdu 1461 3 were be VBD cord-014597-66vd2mdu 1461 4 also also RB cord-014597-66vd2mdu 1461 5 seen see VBN cord-014597-66vd2mdu 1461 6 with with IN cord-014597-66vd2mdu 1461 7 a a DT cord-014597-66vd2mdu 1461 8 modified modify VBN cord-014597-66vd2mdu 1461 9 version version NN cord-014597-66vd2mdu 1461 10 of of IN cord-014597-66vd2mdu 1461 11 vector vector NN cord-014597-66vd2mdu 1461 12 # # $ cord-014597-66vd2mdu 1461 13 39 39 CD cord-014597-66vd2mdu 1461 14 ( ( -LRB- cord-014597-66vd2mdu 1461 15 vector vector NN cord-014597-66vd2mdu 1461 16 # # $ cord-014597-66vd2mdu 1461 17 79 79 CD cord-014597-66vd2mdu 1461 18 , , , cord-014597-66vd2mdu 1461 19 Fig Fig NNP cord-014597-66vd2mdu 1461 20 . . NNP cord-014597-66vd2mdu 1461 21 1 1 CD cord-014597-66vd2mdu 1461 22 ) ) -RRB- cord-014597-66vd2mdu 1461 23 in in IN cord-014597-66vd2mdu 1461 24 which which WDT cord-014597-66vd2mdu 1461 25 the the DT cord-014597-66vd2mdu 1461 26 glutamine glutamine NN cord-014597-66vd2mdu 1461 27 synthethase synthethase NN cord-014597-66vd2mdu 1461 28 selection selection NN cord-014597-66vd2mdu 1461 29 cassette cassette NN cord-014597-66vd2mdu 1461 30 was be VBD cord-014597-66vd2mdu 1461 31 in in IN cord-014597-66vd2mdu 1461 32 the the DT cord-014597-66vd2mdu 1461 33 reverse reverse JJ cord-014597-66vd2mdu 1461 34 orientation orientation NN cord-014597-66vd2mdu 1461 35 . . . cord-014597-66vd2mdu 1462 1 This this DT cord-014597-66vd2mdu 1462 2 second second JJ cord-014597-66vd2mdu 1462 3 screen screen NN cord-014597-66vd2mdu 1462 4 identified identify VBD cord-014597-66vd2mdu 1462 5 vector vector NN cord-014597-66vd2mdu 1462 6 # # $ cord-014597-66vd2mdu 1462 7 77 77 CD cord-014597-66vd2mdu 1462 8 as as IN cord-014597-66vd2mdu 1462 9 the the DT cord-014597-66vd2mdu 1462 10 lead lead JJ cord-014597-66vd2mdu 1462 11 vector vector NN cord-014597-66vd2mdu 1462 12 design design NN cord-014597-66vd2mdu 1462 13 ( ( -LRB- cord-014597-66vd2mdu 1462 14 Fig Fig NNP cord-014597-66vd2mdu 1462 15 . . . cord-014597-66vd2mdu 1462 16 1 1 CD cord-014597-66vd2mdu 1462 17 ) ) -RRB- cord-014597-66vd2mdu 1462 18 . . . cord-014597-66vd2mdu 1463 1 A a DT cord-014597-66vd2mdu 1463 2 full full JJ cord-014597-66vd2mdu 1463 3 comparative comparative JJ cord-014597-66vd2mdu 1463 4 study study NN cord-014597-66vd2mdu 1463 5 of of IN cord-014597-66vd2mdu 1463 6 vector vector NN cord-014597-66vd2mdu 1463 7 # # $ cord-014597-66vd2mdu 1463 8 77 77 CD cord-014597-66vd2mdu 1463 9 and and CC cord-014597-66vd2mdu 1463 10 the the DT cord-014597-66vd2mdu 1463 11 control control NN cord-014597-66vd2mdu 1463 12 vector vector NN cord-014597-66vd2mdu 1463 13 was be VBD cord-014597-66vd2mdu 1463 14 performed perform VBN cord-014597-66vd2mdu 1463 15 , , , cord-014597-66vd2mdu 1463 16 cumulating cumulate VBG cord-014597-66vd2mdu 1463 17 in in IN cord-014597-66vd2mdu 1463 18 the the DT cord-014597-66vd2mdu 1463 19 generation generation NN cord-014597-66vd2mdu 1463 20 and and CC cord-014597-66vd2mdu 1463 21 comparison comparison NN cord-014597-66vd2mdu 1463 22 of of IN cord-014597-66vd2mdu 1463 23 single single JJ cord-014597-66vd2mdu 1463 24 - - HYPH cord-014597-66vd2mdu 1463 25 cell cell NN cord-014597-66vd2mdu 1463 26 clones clone NNS cord-014597-66vd2mdu 1463 27 from from IN cord-014597-66vd2mdu 1463 28 each each DT cord-014597-66vd2mdu 1463 29 . . . cord-014597-66vd2mdu 1464 1 These these DT cord-014597-66vd2mdu 1464 2 studies study NNS cord-014597-66vd2mdu 1464 3 have have VBP cord-014597-66vd2mdu 1464 4 demonstrated demonstrate VBN cord-014597-66vd2mdu 1464 5 the the DT cord-014597-66vd2mdu 1464 6 equivalence equivalence NN cord-014597-66vd2mdu 1464 7 of of IN cord-014597-66vd2mdu 1464 8 these these DT cord-014597-66vd2mdu 1464 9 vectors vector NNS cord-014597-66vd2mdu 1464 10 in in IN cord-014597-66vd2mdu 1464 11 terms term NNS cord-014597-66vd2mdu 1464 12 of of IN cord-014597-66vd2mdu 1464 13 IgG1 IgG1 NNP cord-014597-66vd2mdu 1464 14 titer titer NN cord-014597-66vd2mdu 1464 15 . . . cord-014597-66vd2mdu 1465 1 This this DT cord-014597-66vd2mdu 1465 2 work work NN cord-014597-66vd2mdu 1465 3 has have VBZ cord-014597-66vd2mdu 1465 4 resulted result VBN cord-014597-66vd2mdu 1465 5 in in IN cord-014597-66vd2mdu 1465 6 the the DT cord-014597-66vd2mdu 1465 7 identification identification NN cord-014597-66vd2mdu 1465 8 and and CC cord-014597-66vd2mdu 1465 9 characterization characterization NN cord-014597-66vd2mdu 1465 10 of of IN cord-014597-66vd2mdu 1465 11 a a DT cord-014597-66vd2mdu 1465 12 dual dual JJ cord-014597-66vd2mdu 1465 13 expression expression NN cord-014597-66vd2mdu 1465 14 vector vector NN cord-014597-66vd2mdu 1465 15 with with IN cord-014597-66vd2mdu 1465 16 minimized minimize VBN cord-014597-66vd2mdu 1465 17 similarity similarity NN cord-014597-66vd2mdu 1465 18 between between IN cord-014597-66vd2mdu 1465 19 the the DT cord-014597-66vd2mdu 1465 20 two two CD cord-014597-66vd2mdu 1465 21 expression expression NN cord-014597-66vd2mdu 1465 22 cassettes cassette NNS cord-014597-66vd2mdu 1465 23 , , , cord-014597-66vd2mdu 1465 24 easing ease VBG cord-014597-66vd2mdu 1465 25 the the DT cord-014597-66vd2mdu 1465 26 cloning cloning NN cord-014597-66vd2mdu 1465 27 , , , cord-014597-66vd2mdu 1465 28 propagation propagation NN cord-014597-66vd2mdu 1465 29 and and CC cord-014597-66vd2mdu 1465 30 analysis analysis NN cord-014597-66vd2mdu 1465 31 of of IN cord-014597-66vd2mdu 1465 32 vector vector NN cord-014597-66vd2mdu 1465 33 integration integration NN cord-014597-66vd2mdu 1465 34 in in IN cord-014597-66vd2mdu 1465 35 stable stable JJ cord-014597-66vd2mdu 1465 36 cell cell NN cord-014597-66vd2mdu 1465 37 lines line NNS cord-014597-66vd2mdu 1465 38 while while IN cord-014597-66vd2mdu 1465 39 maintaining maintain VBG cord-014597-66vd2mdu 1465 40 the the DT cord-014597-66vd2mdu 1465 41 high high JJ cord-014597-66vd2mdu 1465 42 , , , cord-014597-66vd2mdu 1465 43 stable stable JJ cord-014597-66vd2mdu 1465 44 expression expression NN cord-014597-66vd2mdu 1465 45 of of IN cord-014597-66vd2mdu 1465 46 the the DT cord-014597-66vd2mdu 1465 47 encoded encode VBN cord-014597-66vd2mdu 1465 48 protein protein NN cord-014597-66vd2mdu 1465 49 of of IN cord-014597-66vd2mdu 1465 50 the the DT cord-014597-66vd2mdu 1465 51 original original JJ cord-014597-66vd2mdu 1465 52 vector vector NN cord-014597-66vd2mdu 1465 53 design design NN cord-014597-66vd2mdu 1465 54 . . . cord-014597-66vd2mdu 1466 1 Background background VB cord-014597-66vd2mdu 1466 2 Traditional traditional JJ cord-014597-66vd2mdu 1466 3 cell cell NN cord-014597-66vd2mdu 1466 4 line line NN cord-014597-66vd2mdu 1466 5 engineering engineering NN cord-014597-66vd2mdu 1466 6 strategies strategy NNS cord-014597-66vd2mdu 1466 7 mainly mainly RB cord-014597-66vd2mdu 1466 8 include include VBP cord-014597-66vd2mdu 1466 9 an an DT cord-014597-66vd2mdu 1466 10 antibiotics antibiotic NNS cord-014597-66vd2mdu 1466 11 resistance resistance NN cord-014597-66vd2mdu 1466 12 selection selection NN cord-014597-66vd2mdu 1466 13 . . . cord-014597-66vd2mdu 1467 1 In in IN cord-014597-66vd2mdu 1467 2 this this DT cord-014597-66vd2mdu 1467 3 process process NN cord-014597-66vd2mdu 1467 4 , , , cord-014597-66vd2mdu 1467 5 cells cell NNS cord-014597-66vd2mdu 1467 6 are be VBP cord-014597-66vd2mdu 1467 7 transfected transfecte VBN cord-014597-66vd2mdu 1467 8 with with IN cord-014597-66vd2mdu 1467 9 the the DT cord-014597-66vd2mdu 1467 10 GoI goi NN cord-014597-66vd2mdu 1467 11 ( ( -LRB- cord-014597-66vd2mdu 1467 12 gene gene NN cord-014597-66vd2mdu 1467 13 of of IN cord-014597-66vd2mdu 1467 14 interest interest NN cord-014597-66vd2mdu 1467 15 ) ) -RRB- cord-014597-66vd2mdu 1467 16 together together RB cord-014597-66vd2mdu 1467 17 with with IN cord-014597-66vd2mdu 1467 18 an an DT cord-014597-66vd2mdu 1467 19 antibiotics antibiotic NNS cord-014597-66vd2mdu 1467 20 resistance resistance NN cord-014597-66vd2mdu 1467 21 gene gene NN cord-014597-66vd2mdu 1467 22 and and CC cord-014597-66vd2mdu 1467 23 those those DT cord-014597-66vd2mdu 1467 24 cells cell NNS cord-014597-66vd2mdu 1467 25 are be VBP cord-014597-66vd2mdu 1467 26 selected select VBN cord-014597-66vd2mdu 1467 27 that that WDT cord-014597-66vd2mdu 1467 28 survive survive VBP cord-014597-66vd2mdu 1467 29 treatment treatment NN cord-014597-66vd2mdu 1467 30 with with IN cord-014597-66vd2mdu 1467 31 the the DT cord-014597-66vd2mdu 1467 32 respective respective JJ cord-014597-66vd2mdu 1467 33 antibiotic antibiotic NN cord-014597-66vd2mdu 1467 34 [ [ -LRB- cord-014597-66vd2mdu 1467 35 1 1 CD cord-014597-66vd2mdu 1467 36 ] ] -RRB- cord-014597-66vd2mdu 1467 37 . . . cord-014597-66vd2mdu 1468 1 Although although IN cord-014597-66vd2mdu 1468 2 the the DT cord-014597-66vd2mdu 1468 3 gene gene NN cord-014597-66vd2mdu 1468 4 responsible responsible JJ cord-014597-66vd2mdu 1468 5 for for IN cord-014597-66vd2mdu 1468 6 the the DT cord-014597-66vd2mdu 1468 7 survival survival NN cord-014597-66vd2mdu 1468 8 of of IN cord-014597-66vd2mdu 1468 9 the the DT cord-014597-66vd2mdu 1468 10 cell cell NN cord-014597-66vd2mdu 1468 11 is be VBZ cord-014597-66vd2mdu 1468 12 transfected transfecte VBN cord-014597-66vd2mdu 1468 13 together together RB cord-014597-66vd2mdu 1468 14 with with IN cord-014597-66vd2mdu 1468 15 the the DT cord-014597-66vd2mdu 1468 16 GoI goi NN cord-014597-66vd2mdu 1468 17 , , , cord-014597-66vd2mdu 1468 18 resistance resistance NN cord-014597-66vd2mdu 1468 19 is be VBZ cord-014597-66vd2mdu 1468 20 not not RB cord-014597-66vd2mdu 1468 21 necessarily necessarily RB cord-014597-66vd2mdu 1468 22 linked link VBN cord-014597-66vd2mdu 1468 23 to to IN cord-014597-66vd2mdu 1468 24 high high JJ cord-014597-66vd2mdu 1468 25 GoI goi NN cord-014597-66vd2mdu 1468 26 expression expression NN cord-014597-66vd2mdu 1468 27 . . . cord-014597-66vd2mdu 1469 1 Thus thus RB cord-014597-66vd2mdu 1469 2 , , , cord-014597-66vd2mdu 1469 3 a a DT cord-014597-66vd2mdu 1469 4 significant significant JJ cord-014597-66vd2mdu 1469 5 proportion proportion NN cord-014597-66vd2mdu 1469 6 of of IN cord-014597-66vd2mdu 1469 7 resistant resistant JJ cord-014597-66vd2mdu 1469 8 cells cell NNS cord-014597-66vd2mdu 1469 9 may may MD cord-014597-66vd2mdu 1469 10 not not RB cord-014597-66vd2mdu 1469 11 express express VB cord-014597-66vd2mdu 1469 12 the the DT cord-014597-66vd2mdu 1469 13 GoI goi NN cord-014597-66vd2mdu 1469 14 at at RB cord-014597-66vd2mdu 1469 15 all all RB cord-014597-66vd2mdu 1469 16 , , , cord-014597-66vd2mdu 1469 17 necessitating necessitate VBG cord-014597-66vd2mdu 1469 18 the the DT cord-014597-66vd2mdu 1469 19 search search NN cord-014597-66vd2mdu 1469 20 for for IN cord-014597-66vd2mdu 1469 21 alternative alternative NN cord-014597-66vd2mdu 1469 22 , , , cord-014597-66vd2mdu 1469 23 more more RBR cord-014597-66vd2mdu 1469 24 closely closely RB cord-014597-66vd2mdu 1469 25 linked link VBN cord-014597-66vd2mdu 1469 26 selection selection NN cord-014597-66vd2mdu 1469 27 systems system NNS cord-014597-66vd2mdu 1469 28 . . . cord-014597-66vd2mdu 1470 1 siRNAs siRNAs NNP cord-014597-66vd2mdu 1471 1 ( ( -LRB- cord-014597-66vd2mdu 1471 2 silencing silence VBG cord-014597-66vd2mdu 1471 3 inducing induce VBG cord-014597-66vd2mdu 1471 4 RNAs rna NNS cord-014597-66vd2mdu 1471 5 ) ) -RRB- cord-014597-66vd2mdu 1471 6 are be VBP cord-014597-66vd2mdu 1471 7 short short JJ cord-014597-66vd2mdu 1471 8 , , , cord-014597-66vd2mdu 1471 9 noncoding noncoding JJ cord-014597-66vd2mdu 1471 10 RNAs rna NNS cord-014597-66vd2mdu 1471 11 that that WDT cord-014597-66vd2mdu 1471 12 can can MD cord-014597-66vd2mdu 1471 13 bind bind VB cord-014597-66vd2mdu 1471 14 to to IN cord-014597-66vd2mdu 1471 15 complementary complementary JJ cord-014597-66vd2mdu 1471 16 mRNA mrna NN cord-014597-66vd2mdu 1471 17 and and CC cord-014597-66vd2mdu 1471 18 inhibit inhibit VB cord-014597-66vd2mdu 1471 19 their -PRON- PRP$ cord-014597-66vd2mdu 1471 20 translation translation NN cord-014597-66vd2mdu 1471 21 . . . cord-014597-66vd2mdu 1472 1 This this DT cord-014597-66vd2mdu 1472 2 function function NN cord-014597-66vd2mdu 1472 3 has have VBZ cord-014597-66vd2mdu 1472 4 been be VBN cord-014597-66vd2mdu 1472 5 used use VBN cord-014597-66vd2mdu 1472 6 in in IN cord-014597-66vd2mdu 1472 7 many many JJ cord-014597-66vd2mdu 1472 8 approaches approach NNS cord-014597-66vd2mdu 1472 9 to to TO cord-014597-66vd2mdu 1472 10 silence silence VB cord-014597-66vd2mdu 1472 11 the the DT cord-014597-66vd2mdu 1472 12 expression expression NN cord-014597-66vd2mdu 1472 13 of of IN cord-014597-66vd2mdu 1472 14 certain certain JJ cord-014597-66vd2mdu 1472 15 genes gene NNS cord-014597-66vd2mdu 1472 16 [ [ -LRB- cord-014597-66vd2mdu 1472 17 2 2 CD cord-014597-66vd2mdu 1472 18 ] ] -RRB- cord-014597-66vd2mdu 1472 19 . . . cord-014597-66vd2mdu 1473 1 With with IN cord-014597-66vd2mdu 1473 2 their -PRON- PRP$ cord-014597-66vd2mdu 1473 3 short short JJ cord-014597-66vd2mdu 1473 4 length length NN cord-014597-66vd2mdu 1473 5 , , , cord-014597-66vd2mdu 1473 6 siRNAs siRNAs NNP cord-014597-66vd2mdu 1473 7 can can MD cord-014597-66vd2mdu 1473 8 be be VB cord-014597-66vd2mdu 1473 9 hidden hide VBN cord-014597-66vd2mdu 1473 10 in in IN cord-014597-66vd2mdu 1473 11 introns intron NNS cord-014597-66vd2mdu 1473 12 ( ( -LRB- cord-014597-66vd2mdu 1473 13 non non JJ cord-014597-66vd2mdu 1473 14 - - JJ cord-014597-66vd2mdu 1473 15 translating translating JJ cord-014597-66vd2mdu 1473 16 regions region NNS cord-014597-66vd2mdu 1473 17 ) ) -RRB- cord-014597-66vd2mdu 1473 18 of of IN cord-014597-66vd2mdu 1473 19 genes gene NNS cord-014597-66vd2mdu 1473 20 , , , cord-014597-66vd2mdu 1473 21 making make VBG cord-014597-66vd2mdu 1473 22 it -PRON- PRP cord-014597-66vd2mdu 1473 23 possible possible JJ cord-014597-66vd2mdu 1473 24 to to TO cord-014597-66vd2mdu 1473 25 couple couple VB cord-014597-66vd2mdu 1473 26 the the DT cord-014597-66vd2mdu 1473 27 expression expression NN cord-014597-66vd2mdu 1473 28 of of IN cord-014597-66vd2mdu 1473 29 a a DT cord-014597-66vd2mdu 1473 30 siRNA sirna NN cord-014597-66vd2mdu 1473 31 to to IN cord-014597-66vd2mdu 1473 32 a a DT cord-014597-66vd2mdu 1473 33 gene gene NN cord-014597-66vd2mdu 1473 34 . . . cord-014597-66vd2mdu 1474 1 This this DT cord-014597-66vd2mdu 1474 2 way way NN cord-014597-66vd2mdu 1474 3 a a DT cord-014597-66vd2mdu 1474 4 cell cell NN cord-014597-66vd2mdu 1474 5 produces produce VBZ cord-014597-66vd2mdu 1474 6 a a DT cord-014597-66vd2mdu 1474 7 correlating correlate VBG cord-014597-66vd2mdu 1474 8 amount amount NN cord-014597-66vd2mdu 1474 9 of of IN cord-014597-66vd2mdu 1474 10 siRNA siRNA NNP cord-014597-66vd2mdu 1474 11 when when WRB cord-014597-66vd2mdu 1474 12 transcribing transcribe VBG cord-014597-66vd2mdu 1474 13 the the DT cord-014597-66vd2mdu 1474 14 gene gene NN cord-014597-66vd2mdu 1474 15 , , , cord-014597-66vd2mdu 1474 16 without without IN cord-014597-66vd2mdu 1474 17 adding add VBG cord-014597-66vd2mdu 1474 18 any any DT cord-014597-66vd2mdu 1474 19 further further JJ cord-014597-66vd2mdu 1474 20 translational translational JJ cord-014597-66vd2mdu 1474 21 burden burden NN cord-014597-66vd2mdu 1474 22 on on IN cord-014597-66vd2mdu 1474 23 the the DT cord-014597-66vd2mdu 1474 24 cell cell NN cord-014597-66vd2mdu 1474 25 . . . cord-014597-66vd2mdu 1475 1 The the DT cord-014597-66vd2mdu 1475 2 co co NN cord-014597-66vd2mdu 1475 3 - - NN cord-014597-66vd2mdu 1475 4 expression expression NN cord-014597-66vd2mdu 1475 5 of of IN cord-014597-66vd2mdu 1475 6 the the DT cord-014597-66vd2mdu 1475 7 siRNA siRNA NNP cord-014597-66vd2mdu 1475 8 can can MD cord-014597-66vd2mdu 1475 9 be be VB cord-014597-66vd2mdu 1475 10 used use VBN cord-014597-66vd2mdu 1475 11 as as IN cord-014597-66vd2mdu 1475 12 a a DT cord-014597-66vd2mdu 1475 13 selective selective JJ cord-014597-66vd2mdu 1475 14 marker marker NN cord-014597-66vd2mdu 1475 15 by by IN cord-014597-66vd2mdu 1475 16 one one CD cord-014597-66vd2mdu 1475 17 of of IN cord-014597-66vd2mdu 1475 18 the the DT cord-014597-66vd2mdu 1475 19 following follow VBG cord-014597-66vd2mdu 1475 20 methods method NNS cord-014597-66vd2mdu 1475 21 : : : cord-014597-66vd2mdu 1475 22 ( ( -LRB- cord-014597-66vd2mdu 1475 23 1 1 LS cord-014597-66vd2mdu 1475 24 ) ) -RRB- cord-014597-66vd2mdu 1475 25 Knock knock VB cord-014597-66vd2mdu 1475 26 - - HYPH cord-014597-66vd2mdu 1475 27 down down NN cord-014597-66vd2mdu 1475 28 of of IN cord-014597-66vd2mdu 1475 29 a a DT cord-014597-66vd2mdu 1475 30 suicide suicide NN cord-014597-66vd2mdu 1475 31 gene gene NN cord-014597-66vd2mdu 1475 32 to to TO cord-014597-66vd2mdu 1475 33 enable enable VB cord-014597-66vd2mdu 1475 34 a a DT cord-014597-66vd2mdu 1475 35 cell cell NN cord-014597-66vd2mdu 1475 36 's 's POS cord-014597-66vd2mdu 1475 37 survival survival NN cord-014597-66vd2mdu 1475 38 after after IN cord-014597-66vd2mdu 1475 39 suicide suicide NN cord-014597-66vd2mdu 1475 40 gene gene NN cord-014597-66vd2mdu 1475 41 mRNA mRNA NNP cord-014597-66vd2mdu 1475 42 transfection transfection NN cord-014597-66vd2mdu 1475 43 , , , cord-014597-66vd2mdu 1475 44 ( ( -LRB- cord-014597-66vd2mdu 1475 45 2 2 LS cord-014597-66vd2mdu 1475 46 ) ) -RRB- cord-014597-66vd2mdu 1475 47 down down IN cord-014597-66vd2mdu 1475 48 - - HYPH cord-014597-66vd2mdu 1475 49 regulation regulation NN cord-014597-66vd2mdu 1475 50 of of IN cord-014597-66vd2mdu 1475 51 a a DT cord-014597-66vd2mdu 1475 52 surface surface NN cord-014597-66vd2mdu 1475 53 marker marker NN cord-014597-66vd2mdu 1475 54 which which WDT cord-014597-66vd2mdu 1475 55 is be VBZ cord-014597-66vd2mdu 1475 56 used use VBN cord-014597-66vd2mdu 1475 57 in in IN cord-014597-66vd2mdu 1475 58 MACS mac NNS cord-014597-66vd2mdu 1475 59 ( ( -LRB- cord-014597-66vd2mdu 1475 60 magnetic magnetic JJ cord-014597-66vd2mdu 1475 61 cell cell NN cord-014597-66vd2mdu 1475 62 separation separation NN cord-014597-66vd2mdu 1475 63 ) ) -RRB- cord-014597-66vd2mdu 1475 64 to to TO cord-014597-66vd2mdu 1475 65 filter filter VB cord-014597-66vd2mdu 1475 66 out out RP cord-014597-66vd2mdu 1475 67 wanted want VBN cord-014597-66vd2mdu 1475 68 or or CC cord-014597-66vd2mdu 1475 69 unwanted unwanted JJ cord-014597-66vd2mdu 1475 70 cells cell NNS cord-014597-66vd2mdu 1475 71 , , , cord-014597-66vd2mdu 1475 72 and and CC cord-014597-66vd2mdu 1475 73 ( ( -LRB- cord-014597-66vd2mdu 1475 74 3 3 LS cord-014597-66vd2mdu 1475 75 ) ) -RRB- cord-014597-66vd2mdu 1475 76 inhibition inhibition NN cord-014597-66vd2mdu 1475 77 of of IN cord-014597-66vd2mdu 1475 78 a a DT cord-014597-66vd2mdu 1475 79 fluorophore fluorophore NN cord-014597-66vd2mdu 1475 80 marker marker NN cord-014597-66vd2mdu 1475 81 for for IN cord-014597-66vd2mdu 1475 82 selection selection NN cord-014597-66vd2mdu 1475 83 using use VBG cord-014597-66vd2mdu 1475 84 FACS FACS NNP cord-014597-66vd2mdu 1475 85 without without IN cord-014597-66vd2mdu 1475 86 product product NN cord-014597-66vd2mdu 1475 87 specific specific JJ cord-014597-66vd2mdu 1475 88 antibodies antibody NNS cord-014597-66vd2mdu 1475 89 . . . cord-014597-66vd2mdu 1476 1 For for IN cord-014597-66vd2mdu 1476 2 siRNA siRNA NNP cord-014597-66vd2mdu 1476 3 based base VBN cord-014597-66vd2mdu 1476 4 cell cell NN cord-014597-66vd2mdu 1476 5 selection selection NN cord-014597-66vd2mdu 1476 6 systems system NNS cord-014597-66vd2mdu 1476 7 , , , cord-014597-66vd2mdu 1476 8 siRNAs siRNAs NNP cord-014597-66vd2mdu 1476 9 replace replace VBP cord-014597-66vd2mdu 1476 10 the the DT cord-014597-66vd2mdu 1476 11 commonly commonly RB cord-014597-66vd2mdu 1476 12 used use VBN cord-014597-66vd2mdu 1476 13 antibiotics antibiotic NNS cord-014597-66vd2mdu 1476 14 resistance resistance NN cord-014597-66vd2mdu 1476 15 as as IN cord-014597-66vd2mdu 1476 16 a a DT cord-014597-66vd2mdu 1476 17 marker marker NN cord-014597-66vd2mdu 1476 18 . . . cord-014597-66vd2mdu 1477 1 Cells cell NNS cord-014597-66vd2mdu 1477 2 that that WDT cord-014597-66vd2mdu 1477 3 produce produce VBP cord-014597-66vd2mdu 1477 4 GoI goi NN cord-014597-66vd2mdu 1477 5 will will MD cord-014597-66vd2mdu 1477 6 also also RB cord-014597-66vd2mdu 1477 7 produce produce VB cord-014597-66vd2mdu 1477 8 the the DT cord-014597-66vd2mdu 1477 9 siRNA sirna NN cord-014597-66vd2mdu 1477 10 that that WDT cord-014597-66vd2mdu 1477 11 protects protect VBZ cord-014597-66vd2mdu 1477 12 the the DT cord-014597-66vd2mdu 1477 13 cell cell NN cord-014597-66vd2mdu 1477 14 from from IN cord-014597-66vd2mdu 1477 15 a a DT cord-014597-66vd2mdu 1477 16 suicide suicide NN cord-014597-66vd2mdu 1477 17 gene gene NN cord-014597-66vd2mdu 1477 18 . . . cord-014597-66vd2mdu 1478 1 The the DT cord-014597-66vd2mdu 1478 2 selection selection NN cord-014597-66vd2mdu 1478 3 protein protein NN cord-014597-66vd2mdu 1478 4 ( ( -LRB- cord-014597-66vd2mdu 1478 5 suicide suicide NN cord-014597-66vd2mdu 1478 6 genes gene NNS cord-014597-66vd2mdu 1478 7 , , , cord-014597-66vd2mdu 1478 8 fluorophores fluorophore NNS cord-014597-66vd2mdu 1478 9 , , , cord-014597-66vd2mdu 1478 10 surface surface NN cord-014597-66vd2mdu 1478 11 markers marker NNS cord-014597-66vd2mdu 1478 12 , , , cord-014597-66vd2mdu 1478 13 etc etc FW cord-014597-66vd2mdu 1478 14 . . . cord-014597-66vd2mdu 1478 15 ) ) -RRB- cord-014597-66vd2mdu 1478 16 is be VBZ cord-014597-66vd2mdu 1478 17 transfected transfecte VBN cord-014597-66vd2mdu 1478 18 as as IN cord-014597-66vd2mdu 1478 19 mRNA mRNA NNP cord-014597-66vd2mdu 1478 20 and and CC cord-014597-66vd2mdu 1478 21 is be VBZ cord-014597-66vd2mdu 1478 22 only only RB cord-014597-66vd2mdu 1478 23 expressed express VBN cord-014597-66vd2mdu 1478 24 during during IN cord-014597-66vd2mdu 1478 25 selection selection NN cord-014597-66vd2mdu 1478 26 . . . cord-014597-66vd2mdu 1479 1 The the DT cord-014597-66vd2mdu 1479 2 general general JJ cord-014597-66vd2mdu 1479 3 process process NN cord-014597-66vd2mdu 1479 4 is be VBZ cord-014597-66vd2mdu 1479 5 outlined outline VBN cord-014597-66vd2mdu 1479 6 in in IN cord-014597-66vd2mdu 1479 7 Fig Fig NNP cord-014597-66vd2mdu 1479 8 . . . cord-014597-66vd2mdu 1480 1 1 1 LS cord-014597-66vd2mdu 1480 2 . . . cord-014597-66vd2mdu 1481 1 ( ( -LRB- cord-014597-66vd2mdu 1481 2 A a NN cord-014597-66vd2mdu 1481 3 ) ) -RRB- cord-014597-66vd2mdu 1482 1 The the DT cord-014597-66vd2mdu 1482 2 traditional traditional JJ cord-014597-66vd2mdu 1482 3 antibiotics antibiotic NNS cord-014597-66vd2mdu 1482 4 resistance resistance NN cord-014597-66vd2mdu 1482 5 marker marker NN cord-014597-66vd2mdu 1482 6 is be VBZ cord-014597-66vd2mdu 1482 7 replaced replace VBN cord-014597-66vd2mdu 1482 8 by by IN cord-014597-66vd2mdu 1482 9 an an DT cord-014597-66vd2mdu 1482 10 siRNA siRNA NNP cord-014597-66vd2mdu 1482 11 , , , cord-014597-66vd2mdu 1482 12 which which WDT cord-014597-66vd2mdu 1482 13 is be VBZ cord-014597-66vd2mdu 1482 14 cotranscribed cotranscribe VBN cord-014597-66vd2mdu 1482 15 with with IN cord-014597-66vd2mdu 1482 16 the the DT cord-014597-66vd2mdu 1482 17 GoI. GoI. NNP cord-014597-66vd2mdu 1483 1 Unlike unlike IN cord-014597-66vd2mdu 1483 2 in in IN cord-014597-66vd2mdu 1483 3 antibiotic antibiotic JJ cord-014597-66vd2mdu 1483 4 resistance resistance NN cord-014597-66vd2mdu 1483 5 , , , cord-014597-66vd2mdu 1483 6 the the DT cord-014597-66vd2mdu 1483 7 marker marker NN cord-014597-66vd2mdu 1483 8 here here RB cord-014597-66vd2mdu 1483 9 is be VBZ cord-014597-66vd2mdu 1483 10 not not RB cord-014597-66vd2mdu 1483 11 a a DT cord-014597-66vd2mdu 1483 12 protein protein NN cord-014597-66vd2mdu 1483 13 , , , cord-014597-66vd2mdu 1483 14 reducing reduce VBG cord-014597-66vd2mdu 1483 15 the the DT cord-014597-66vd2mdu 1483 16 translational translational JJ cord-014597-66vd2mdu 1483 17 burden burden NN cord-014597-66vd2mdu 1483 18 and and CC cord-014597-66vd2mdu 1483 19 providing provide VBG cord-014597-66vd2mdu 1483 20 more more JJR cord-014597-66vd2mdu 1483 21 resources resource NNS cord-014597-66vd2mdu 1483 22 for for IN cord-014597-66vd2mdu 1483 23 GoI goi NN cord-014597-66vd2mdu 1483 24 production production NN cord-014597-66vd2mdu 1483 25 [ [ -LRB- cord-014597-66vd2mdu 1483 26 3 3 CD cord-014597-66vd2mdu 1483 27 ] ] -RRB- cord-014597-66vd2mdu 1483 28 . . . cord-014597-66vd2mdu 1483 29 _SP cord-014597-66vd2mdu 1484 1 Transfection transfection NN cord-014597-66vd2mdu 1484 2 with with IN cord-014597-66vd2mdu 1484 3 the the DT cord-014597-66vd2mdu 1484 4 suicide suicide NN cord-014597-66vd2mdu 1484 5 gene gene NN cord-014597-66vd2mdu 1484 6 proved prove VBD cord-014597-66vd2mdu 1484 7 to to TO cord-014597-66vd2mdu 1484 8 be be VB cord-014597-66vd2mdu 1484 9 100 100 CD cord-014597-66vd2mdu 1484 10 % % NN cord-014597-66vd2mdu 1484 11 lethal lethal JJ cord-014597-66vd2mdu 1484 12 within within IN cord-014597-66vd2mdu 1484 13 2 2 CD cord-014597-66vd2mdu 1484 14 days day NNS cord-014597-66vd2mdu 1484 15 , , , cord-014597-66vd2mdu 1484 16 with with IN cord-014597-66vd2mdu 1484 17 no no DT cord-014597-66vd2mdu 1484 18 outgrowth outgrowth NN cord-014597-66vd2mdu 1484 19 over over IN cord-014597-66vd2mdu 1484 20 two two CD cord-014597-66vd2mdu 1484 21 weeks week NNS cord-014597-66vd2mdu 1484 22 . . . cord-014597-66vd2mdu 1485 1 Protection protection NN cord-014597-66vd2mdu 1485 2 by by IN cord-014597-66vd2mdu 1485 3 expression expression NN cord-014597-66vd2mdu 1485 4 of of IN cord-014597-66vd2mdu 1485 5 the the DT cord-014597-66vd2mdu 1485 6 siRNA siRNA NNP cord-014597-66vd2mdu 1485 7 was be VBD cord-014597-66vd2mdu 1485 8 shown show VBN cord-014597-66vd2mdu 1485 9 to to TO cord-014597-66vd2mdu 1485 10 be be VB cord-014597-66vd2mdu 1485 11 efficient efficient JJ cord-014597-66vd2mdu 1485 12 . . . cord-014597-66vd2mdu 1486 1 Currently currently RB cord-014597-66vd2mdu 1486 2 a a DT cord-014597-66vd2mdu 1486 3 comparison comparison NN cord-014597-66vd2mdu 1486 4 of of IN cord-014597-66vd2mdu 1486 5 stable stable JJ cord-014597-66vd2mdu 1486 6 cell cell NN cord-014597-66vd2mdu 1486 7 line line NN cord-014597-66vd2mdu 1486 8 development development NN cord-014597-66vd2mdu 1486 9 programs program NNS cord-014597-66vd2mdu 1486 10 based base VBN cord-014597-66vd2mdu 1486 11 on on IN cord-014597-66vd2mdu 1486 12 siRNA siRNA NNP cord-014597-66vd2mdu 1486 13 selection selection NN cord-014597-66vd2mdu 1486 14 and and CC cord-014597-66vd2mdu 1486 15 neomycin neomycin NN cord-014597-66vd2mdu 1486 16 selection selection NN cord-014597-66vd2mdu 1486 17 is be VBZ cord-014597-66vd2mdu 1486 18 ongoing ongoing JJ cord-014597-66vd2mdu 1486 19 . . . cord-014597-66vd2mdu 1487 1 Conclusions conclusion NNS cord-014597-66vd2mdu 1488 1 The the DT cord-014597-66vd2mdu 1488 2 novel novel NN cord-014597-66vd2mdu 1488 3 selection selection NN cord-014597-66vd2mdu 1488 4 system system NN cord-014597-66vd2mdu 1488 5 should should MD cord-014597-66vd2mdu 1488 6 speed speed VB cord-014597-66vd2mdu 1488 7 up up RP cord-014597-66vd2mdu 1488 8 cell cell NN cord-014597-66vd2mdu 1488 9 line line NN cord-014597-66vd2mdu 1488 10 development development NN cord-014597-66vd2mdu 1488 11 , , , cord-014597-66vd2mdu 1488 12 as as IN cord-014597-66vd2mdu 1488 13 the the DT cord-014597-66vd2mdu 1488 14 system system NN cord-014597-66vd2mdu 1488 15 kills kill VBZ cord-014597-66vd2mdu 1488 16 rapidly rapidly RB cord-014597-66vd2mdu 1488 17 and and CC cord-014597-66vd2mdu 1488 18 directly directly RB cord-014597-66vd2mdu 1488 19 selects select VBZ cord-014597-66vd2mdu 1488 20 for for IN cord-014597-66vd2mdu 1488 21 cells cell NNS cord-014597-66vd2mdu 1488 22 transcribing transcribe VBG cord-014597-66vd2mdu 1488 23 the the DT cord-014597-66vd2mdu 1488 24 product product NN cord-014597-66vd2mdu 1488 25 gene gene NN cord-014597-66vd2mdu 1488 26 on on IN cord-014597-66vd2mdu 1488 27 a a DT cord-014597-66vd2mdu 1488 28 high high JJ cord-014597-66vd2mdu 1488 29 level level NN cord-014597-66vd2mdu 1488 30 . . . cord-014597-66vd2mdu 1489 1 We -PRON- PRP cord-014597-66vd2mdu 1489 2 expect expect VBP cord-014597-66vd2mdu 1489 3 to to TO cord-014597-66vd2mdu 1489 4 see see VB cord-014597-66vd2mdu 1489 5 more more JJR cord-014597-66vd2mdu 1489 6 high high JJ cord-014597-66vd2mdu 1489 7 producers producer NNS cord-014597-66vd2mdu 1489 8 earlier early RBR cord-014597-66vd2mdu 1489 9 in in IN cord-014597-66vd2mdu 1489 10 the the DT cord-014597-66vd2mdu 1489 11 process process NN cord-014597-66vd2mdu 1489 12 , , , cord-014597-66vd2mdu 1489 13 which which WDT cord-014597-66vd2mdu 1489 14 will will MD cord-014597-66vd2mdu 1489 15 allow allow VB cord-014597-66vd2mdu 1489 16 for for IN cord-014597-66vd2mdu 1489 17 an an DT cord-014597-66vd2mdu 1489 18 easier easy JJR cord-014597-66vd2mdu 1489 19 and and CC cord-014597-66vd2mdu 1489 20 faster fast JJR cord-014597-66vd2mdu 1489 21 selection selection NN cord-014597-66vd2mdu 1489 22 in in IN cord-014597-66vd2mdu 1489 23 the the DT cord-014597-66vd2mdu 1489 24 following follow VBG cord-014597-66vd2mdu 1489 25 steps step NNS cord-014597-66vd2mdu 1489 26 . . . cord-014597-66vd2mdu 1490 1 siRNA siRNA NNP cord-014597-66vd2mdu 1490 2 based base VBN cord-014597-66vd2mdu 1490 3 selection selection NN cord-014597-66vd2mdu 1490 4 offers offer VBZ cord-014597-66vd2mdu 1490 5 great great JJ cord-014597-66vd2mdu 1490 6 opportunities opportunity NNS cord-014597-66vd2mdu 1490 7 . . . cord-014597-66vd2mdu 1491 1 By by IN cord-014597-66vd2mdu 1491 2 directly directly RB cord-014597-66vd2mdu 1491 3 selecting select VBG cord-014597-66vd2mdu 1491 4 based base VBN cord-014597-66vd2mdu 1491 5 on on IN cord-014597-66vd2mdu 1491 6 GoI GoI NNP cord-014597-66vd2mdu 1491 7 transcription transcription NN cord-014597-66vd2mdu 1491 8 and and CC cord-014597-66vd2mdu 1491 9 not not RB cord-014597-66vd2mdu 1491 10 a a DT cord-014597-66vd2mdu 1491 11 proxy proxy JJ cord-014597-66vd2mdu 1491 12 marker marker NN cord-014597-66vd2mdu 1491 13 , , , cord-014597-66vd2mdu 1491 14 we -PRON- PRP cord-014597-66vd2mdu 1491 15 expect expect VBP cord-014597-66vd2mdu 1491 16 more more RBR cord-014597-66vd2mdu 1491 17 relevant relevant JJ cord-014597-66vd2mdu 1491 18 cells cell NNS cord-014597-66vd2mdu 1491 19 on on IN cord-014597-66vd2mdu 1491 20 a a DT cord-014597-66vd2mdu 1491 21 pool pool NN cord-014597-66vd2mdu 1491 22 level level NN cord-014597-66vd2mdu 1491 23 . . . cord-014597-66vd2mdu 1492 1 In in IN cord-014597-66vd2mdu 1492 2 addition addition NN cord-014597-66vd2mdu 1492 3 , , , cord-014597-66vd2mdu 1492 4 the the DT cord-014597-66vd2mdu 1492 5 elimination elimination NN cord-014597-66vd2mdu 1492 6 of of IN cord-014597-66vd2mdu 1492 7 an an DT cord-014597-66vd2mdu 1492 8 antibiotics antibiotic NNS cord-014597-66vd2mdu 1492 9 resistance resistance NN cord-014597-66vd2mdu 1492 10 allows allow VBZ cord-014597-66vd2mdu 1492 11 more more JJR cord-014597-66vd2mdu 1492 12 cellular cellular JJ cord-014597-66vd2mdu 1492 13 resources resource NNS cord-014597-66vd2mdu 1492 14 for for IN cord-014597-66vd2mdu 1492 15 GoI GoI NNP cord-014597-66vd2mdu 1492 16 production production NN cord-014597-66vd2mdu 1492 17 . . . cord-014597-66vd2mdu 1493 1 The the DT cord-014597-66vd2mdu 1493 2 system system NN cord-014597-66vd2mdu 1493 3 offers offer VBZ cord-014597-66vd2mdu 1493 4 multiple multiple JJ cord-014597-66vd2mdu 1493 5 ways way NNS cord-014597-66vd2mdu 1493 6 of of IN cord-014597-66vd2mdu 1493 7 application application NN cord-014597-66vd2mdu 1493 8 , , , cord-014597-66vd2mdu 1493 9 either either CC cord-014597-66vd2mdu 1493 10 by by IN cord-014597-66vd2mdu 1493 11 enriching enrich VBG cord-014597-66vd2mdu 1493 12 wanted want VBD cord-014597-66vd2mdu 1493 13 , , , cord-014597-66vd2mdu 1493 14 or or CC cord-014597-66vd2mdu 1493 15 depleting deplete VBG cord-014597-66vd2mdu 1493 16 unwanted unwanted JJ cord-014597-66vd2mdu 1493 17 cells cell NNS cord-014597-66vd2mdu 1493 18 . . . cord-014597-66vd2mdu 1494 1 Background Background NNP cord-014597-66vd2mdu 1494 2 Single single JJ cord-014597-66vd2mdu 1494 3 - - HYPH cord-014597-66vd2mdu 1494 4 cell cell NN cord-014597-66vd2mdu 1494 5 cloning cloning NN cord-014597-66vd2mdu 1494 6 is be VBZ cord-014597-66vd2mdu 1494 7 an an DT cord-014597-66vd2mdu 1494 8 essential essential JJ cord-014597-66vd2mdu 1494 9 step step NN cord-014597-66vd2mdu 1494 10 used use VBN cord-014597-66vd2mdu 1494 11 in in IN cord-014597-66vd2mdu 1494 12 the the DT cord-014597-66vd2mdu 1494 13 upstream upstream JJ cord-014597-66vd2mdu 1494 14 development development NN cord-014597-66vd2mdu 1494 15 of of IN cord-014597-66vd2mdu 1494 16 transformed transform VBN cord-014597-66vd2mdu 1494 17 cell cell NN cord-014597-66vd2mdu 1494 18 lines line NNS cord-014597-66vd2mdu 1494 19 for for IN cord-014597-66vd2mdu 1494 20 therapeutic therapeutic JJ cord-014597-66vd2mdu 1494 21 protein protein NN cord-014597-66vd2mdu 1494 22 production production NN cord-014597-66vd2mdu 1494 23 . . . cord-014597-66vd2mdu 1495 1 While while IN cord-014597-66vd2mdu 1495 2 single single JJ cord-014597-66vd2mdu 1495 3 - - HYPH cord-014597-66vd2mdu 1495 4 cell cell NN cord-014597-66vd2mdu 1495 5 clones clone NNS cord-014597-66vd2mdu 1495 6 are be VBP cord-014597-66vd2mdu 1495 7 typically typically RB cord-014597-66vd2mdu 1495 8 used use VBN cord-014597-66vd2mdu 1495 9 to to TO cord-014597-66vd2mdu 1495 10 ensure ensure VB cord-014597-66vd2mdu 1495 11 product product NN cord-014597-66vd2mdu 1495 12 consistency consistency NN cord-014597-66vd2mdu 1495 13 , , , cord-014597-66vd2mdu 1495 14 such such JJ cord-014597-66vd2mdu 1495 15 low low JJ cord-014597-66vd2mdu 1495 16 cell cell NN cord-014597-66vd2mdu 1495 17 density density NN cord-014597-66vd2mdu 1495 18 cultures culture NNS cord-014597-66vd2mdu 1495 19 present present VBP cord-014597-66vd2mdu 1495 20 a a DT cord-014597-66vd2mdu 1495 21 survival survival NN cord-014597-66vd2mdu 1495 22 challenge challenge NN cord-014597-66vd2mdu 1495 23 ; ; : cord-014597-66vd2mdu 1495 24 cells cell NNS cord-014597-66vd2mdu 1495 25 grow grow VBP cord-014597-66vd2mdu 1495 26 more more RBR cord-014597-66vd2mdu 1495 27 slowly slowly RB cord-014597-66vd2mdu 1495 28 or or CC cord-014597-66vd2mdu 1495 29 may may MD cord-014597-66vd2mdu 1495 30 even even RB cord-014597-66vd2mdu 1495 31 not not RB cord-014597-66vd2mdu 1495 32 survive survive VB cord-014597-66vd2mdu 1495 33 at at IN cord-014597-66vd2mdu 1495 34 low low JJ cord-014597-66vd2mdu 1495 35 densities density NNS cord-014597-66vd2mdu 1495 36 in in IN cord-014597-66vd2mdu 1495 37 protein protein NN cord-014597-66vd2mdu 1495 38 - - HYPH cord-014597-66vd2mdu 1495 39 free free JJ cord-014597-66vd2mdu 1495 40 media medium NNS cord-014597-66vd2mdu 1495 41 , , , cord-014597-66vd2mdu 1495 42 costing cost VBG cord-014597-66vd2mdu 1495 43 the the DT cord-014597-66vd2mdu 1495 44 industry industry NN cord-014597-66vd2mdu 1495 45 time time NN cord-014597-66vd2mdu 1495 46 and and CC cord-014597-66vd2mdu 1495 47 money money NN cord-014597-66vd2mdu 1495 48 and and CC cord-014597-66vd2mdu 1495 49 limiting limit VBG cord-014597-66vd2mdu 1495 50 the the DT cord-014597-66vd2mdu 1495 51 pool pool NN cord-014597-66vd2mdu 1495 52 of of IN cord-014597-66vd2mdu 1495 53 candidate candidate NN cord-014597-66vd2mdu 1495 54 colonies colony NNS cord-014597-66vd2mdu 1495 55 for for IN cord-014597-66vd2mdu 1495 56 choice choice NN cord-014597-66vd2mdu 1495 57 of of IN cord-014597-66vd2mdu 1495 58 production production NN cord-014597-66vd2mdu 1495 59 clones clone NNS cord-014597-66vd2mdu 1495 60 [ [ -LRB- cord-014597-66vd2mdu 1495 61 1 1 CD cord-014597-66vd2mdu 1495 62 , , , cord-014597-66vd2mdu 1495 63 2 2 CD cord-014597-66vd2mdu 1495 64 ] ] -RRB- cord-014597-66vd2mdu 1495 65 . . . cord-014597-66vd2mdu 1496 1 To to TO cord-014597-66vd2mdu 1496 2 address address VB cord-014597-66vd2mdu 1496 3 this this DT cord-014597-66vd2mdu 1496 4 problem problem NN cord-014597-66vd2mdu 1496 5 , , , cord-014597-66vd2mdu 1496 6 we -PRON- PRP cord-014597-66vd2mdu 1496 7 aimed aim VBD cord-014597-66vd2mdu 1496 8 to to TO cord-014597-66vd2mdu 1496 9 develop develop VB cord-014597-66vd2mdu 1496 10 a a DT cord-014597-66vd2mdu 1496 11 highly highly RB cord-014597-66vd2mdu 1496 12 efficient efficient JJ cord-014597-66vd2mdu 1496 13 serum serum NN cord-014597-66vd2mdu 1496 14 - - HYPH cord-014597-66vd2mdu 1496 15 free free JJ cord-014597-66vd2mdu 1496 16 medium medium NN cord-014597-66vd2mdu 1496 17 suitable suitable JJ cord-014597-66vd2mdu 1496 18 for for IN cord-014597-66vd2mdu 1496 19 optimising optimise VBG cord-014597-66vd2mdu 1496 20 single single JJ cord-014597-66vd2mdu 1496 21 - - HYPH cord-014597-66vd2mdu 1496 22 cell cell NN cord-014597-66vd2mdu 1496 23 cloning cloning NN cord-014597-66vd2mdu 1496 24 efficiency efficiency NN cord-014597-66vd2mdu 1496 25 by by IN cord-014597-66vd2mdu 1496 26 studying study VBG cord-014597-66vd2mdu 1496 27 a a DT cord-014597-66vd2mdu 1496 28 range range NN cord-014597-66vd2mdu 1496 29 of of IN cord-014597-66vd2mdu 1496 30 conditioned condition VBN cord-014597-66vd2mdu 1496 31 media medium NNS cord-014597-66vd2mdu 1496 32 ( ( -LRB- cord-014597-66vd2mdu 1496 33 CM CM NNP cord-014597-66vd2mdu 1496 34 ) ) -RRB- cord-014597-66vd2mdu 1496 35 samples sample NNS cord-014597-66vd2mdu 1496 36 isolated isolate VBN cord-014597-66vd2mdu 1496 37 from from IN cord-014597-66vd2mdu 1496 38 different different JJ cord-014597-66vd2mdu 1496 39 Chinese chinese JJ cord-014597-66vd2mdu 1496 40 Hamster Hamster NNP cord-014597-66vd2mdu 1496 41 Ovary Ovary NNP cord-014597-66vd2mdu 1496 42 ( ( -LRB- cord-014597-66vd2mdu 1496 43 CHO CHO NNP cord-014597-66vd2mdu 1496 44 ) ) -RRB- cord-014597-66vd2mdu 1496 45 cell cell NN cord-014597-66vd2mdu 1496 46 lines line NNS cord-014597-66vd2mdu 1496 47 . . . cord-014597-66vd2mdu 1497 1 Materials material NNS cord-014597-66vd2mdu 1497 2 and and CC cord-014597-66vd2mdu 1497 3 methods method NNS cord-014597-66vd2mdu 1497 4 CHO CHO NNP cord-014597-66vd2mdu 1497 5 - - HYPH cord-014597-66vd2mdu 1497 6 S S NNP cord-014597-66vd2mdu 1497 7 , , , cord-014597-66vd2mdu 1497 8 DG44 DG44 NNP cord-014597-66vd2mdu 1497 9 and and CC cord-014597-66vd2mdu 1497 10 CHO CHO NNP cord-014597-66vd2mdu 1497 11 - - HYPH cord-014597-66vd2mdu 1497 12 K1 K1 NNP cord-014597-66vd2mdu 1497 13 were be VBD cord-014597-66vd2mdu 1497 14 adapted adapt VBN cord-014597-66vd2mdu 1497 15 to to IN cord-014597-66vd2mdu 1497 16 CHO CHO NNP cord-014597-66vd2mdu 1497 17 - - HYPH cord-014597-66vd2mdu 1497 18 S S NNP cord-014597-66vd2mdu 1497 19 SFM SFM NNP cord-014597-66vd2mdu 1497 20 - - HYPH cord-014597-66vd2mdu 1497 21 II II NNP cord-014597-66vd2mdu 1498 1 ( ( -LRB- cord-014597-66vd2mdu 1498 2 Gibco Gibco NNP cord-014597-66vd2mdu 1498 3 ) ) -RRB- cord-014597-66vd2mdu 1498 4 medium medium NN cord-014597-66vd2mdu 1498 5 for for IN cord-014597-66vd2mdu 1498 6 a a DT cord-014597-66vd2mdu 1498 7 minimum minimum NN cord-014597-66vd2mdu 1498 8 of of IN cord-014597-66vd2mdu 1498 9 three three CD cord-014597-66vd2mdu 1498 10 passages passage NNS cord-014597-66vd2mdu 1498 11 . . . cord-014597-66vd2mdu 1499 1 Conditioned conditioned JJ cord-014597-66vd2mdu 1499 2 media medium NNS cord-014597-66vd2mdu 1499 3 was be VBD cord-014597-66vd2mdu 1499 4 then then RB cord-014597-66vd2mdu 1499 5 collected collect VBN cord-014597-66vd2mdu 1499 6 when when WRB cord-014597-66vd2mdu 1499 7 the the DT cord-014597-66vd2mdu 1499 8 cultures culture NNS cord-014597-66vd2mdu 1499 9 reached reach VBD cord-014597-66vd2mdu 1499 10 a a DT cord-014597-66vd2mdu 1499 11 cell cell NN cord-014597-66vd2mdu 1499 12 density density NN cord-014597-66vd2mdu 1499 13 of of IN cord-014597-66vd2mdu 1499 14 1x10 1x10 CD cord-014597-66vd2mdu 1499 15 6 6 CD cord-014597-66vd2mdu 1499 16 cells cell NNS cord-014597-66vd2mdu 1499 17 / / SYM cord-014597-66vd2mdu 1499 18 ml ml NN cord-014597-66vd2mdu 1499 19 ( ( -LRB- cord-014597-66vd2mdu 1499 20 typically typically RB cord-014597-66vd2mdu 1499 21 day day NN cord-014597-66vd2mdu 1499 22 2-day 2-day JJ cord-014597-66vd2mdu 1499 23 3 3 CD cord-014597-66vd2mdu 1499 24 depending depend VBG cord-014597-66vd2mdu 1499 25 on on IN cord-014597-66vd2mdu 1499 26 the the DT cord-014597-66vd2mdu 1499 27 growth growth NN cord-014597-66vd2mdu 1499 28 profiles profile NNS cord-014597-66vd2mdu 1499 29 of of IN cord-014597-66vd2mdu 1499 30 each each DT cord-014597-66vd2mdu 1499 31 cell cell NN cord-014597-66vd2mdu 1499 32 line line NN cord-014597-66vd2mdu 1499 33 and and CC cord-014597-66vd2mdu 1499 34 whether whether IN cord-014597-66vd2mdu 1499 35 they -PRON- PRP cord-014597-66vd2mdu 1499 36 grew grow VBD cord-014597-66vd2mdu 1499 37 in in IN cord-014597-66vd2mdu 1499 38 suspension suspension NN cord-014597-66vd2mdu 1499 39 or or CC cord-014597-66vd2mdu 1499 40 attached attach VBN cord-014597-66vd2mdu 1499 41 conditions condition NNS cord-014597-66vd2mdu 1499 42 ) ) -RRB- cord-014597-66vd2mdu 1499 43 . . . cord-014597-66vd2mdu 1500 1 Samples sample NNS cord-014597-66vd2mdu 1500 2 were be VBD cord-014597-66vd2mdu 1500 3 then then RB cord-014597-66vd2mdu 1500 4 centrifuged centrifuge VBN cord-014597-66vd2mdu 1500 5 twice twice RB cord-014597-66vd2mdu 1500 6 to to TO cord-014597-66vd2mdu 1500 7 remove remove VB cord-014597-66vd2mdu 1500 8 cell cell NN cord-014597-66vd2mdu 1500 9 pellet pellet NN cord-014597-66vd2mdu 1500 10 / / SYM cord-014597-66vd2mdu 1500 11 debris debris NN cord-014597-66vd2mdu 1500 12 and and CC cord-014597-66vd2mdu 1500 13 stored store VBN cord-014597-66vd2mdu 1500 14 at at IN cord-014597-66vd2mdu 1500 15 -20 -20 NNP cord-014597-66vd2mdu 1500 16 ° ° NN cord-014597-66vd2mdu 1500 17 C C NNP cord-014597-66vd2mdu 1500 18 . . . cord-014597-66vd2mdu 1501 1 The the DT cord-014597-66vd2mdu 1501 2 ability ability NN cord-014597-66vd2mdu 1501 3 of of IN cord-014597-66vd2mdu 1501 4 conditioned condition VBN cord-014597-66vd2mdu 1501 5 media medium NNS cord-014597-66vd2mdu 1501 6 to to TO cord-014597-66vd2mdu 1501 7 support support VB cord-014597-66vd2mdu 1501 8 CHO CHO NNP cord-014597-66vd2mdu 1501 9 colony colony NN cord-014597-66vd2mdu 1501 10 formation formation NN cord-014597-66vd2mdu 1501 11 was be VBD cord-014597-66vd2mdu 1501 12 then then RB cord-014597-66vd2mdu 1501 13 assayed assay VBN cord-014597-66vd2mdu 1501 14 using use VBG cord-014597-66vd2mdu 1501 15 96-well 96-well CD cord-014597-66vd2mdu 1501 16 plates plate NNS cord-014597-66vd2mdu 1501 17 , , , cord-014597-66vd2mdu 1501 18 seeding seed VBG cord-014597-66vd2mdu 1501 19 the the DT cord-014597-66vd2mdu 1501 20 cells cell NNS cord-014597-66vd2mdu 1501 21 at at IN cord-014597-66vd2mdu 1501 22 low low JJ cord-014597-66vd2mdu 1501 23 cell cell NN cord-014597-66vd2mdu 1501 24 density density NN cord-014597-66vd2mdu 1501 25 ( ( -LRB- cord-014597-66vd2mdu 1501 26 1 1 CD cord-014597-66vd2mdu 1501 27 - - HYPH cord-014597-66vd2mdu 1501 28 10cells 10cells CD cord-014597-66vd2mdu 1501 29 / / SYM cord-014597-66vd2mdu 1501 30 well well RB cord-014597-66vd2mdu 1501 31 ) ) -RRB- cord-014597-66vd2mdu 1501 32 by by IN cord-014597-66vd2mdu 1501 33 diluting dilute VBG cord-014597-66vd2mdu 1501 34 down down RP cord-014597-66vd2mdu 1501 35 CHO CHO NNP cord-014597-66vd2mdu 1501 36 cultures culture NNS cord-014597-66vd2mdu 1501 37 in in IN cord-014597-66vd2mdu 1501 38 media medium NNS cord-014597-66vd2mdu 1501 39 / / SYM cord-014597-66vd2mdu 1501 40 conditioned condition VBN cord-014597-66vd2mdu 1501 41 media medium NNS cord-014597-66vd2mdu 1501 42 . . . cord-014597-66vd2mdu 1502 1 After after IN cord-014597-66vd2mdu 1502 2 incubation incubation NN cord-014597-66vd2mdu 1502 3 at at IN cord-014597-66vd2mdu 1502 4 37 37 CD cord-014597-66vd2mdu 1502 5 ° ° NN cord-014597-66vd2mdu 1502 6 C c NN cord-014597-66vd2mdu 1502 7 for for IN cord-014597-66vd2mdu 1502 8 10 10 CD cord-014597-66vd2mdu 1502 9 days day NNS cord-014597-66vd2mdu 1502 10 , , , cord-014597-66vd2mdu 1502 11 cloning clone VBG cord-014597-66vd2mdu 1502 12 efficiency efficiency NN cord-014597-66vd2mdu 1502 13 was be VBD cord-014597-66vd2mdu 1502 14 assayed assay VBN cord-014597-66vd2mdu 1502 15 using use VBG cord-014597-66vd2mdu 1502 16 a a DT cord-014597-66vd2mdu 1502 17 standard standard JJ cord-014597-66vd2mdu 1502 18 XTT XTT NNP cord-014597-66vd2mdu 1502 19 assay assay NN cord-014597-66vd2mdu 1502 20 . . . cord-014597-66vd2mdu 1503 1 Initial initial JJ cord-014597-66vd2mdu 1503 2 screening screening NN cord-014597-66vd2mdu 1503 3 of of IN cord-014597-66vd2mdu 1503 4 the the DT cord-014597-66vd2mdu 1503 5 nine nine CD cord-014597-66vd2mdu 1503 6 CM cm NN cord-014597-66vd2mdu 1503 7 samples sample NNS cord-014597-66vd2mdu 1503 8 was be VBD cord-014597-66vd2mdu 1503 9 performed perform VBN cord-014597-66vd2mdu 1503 10 using use VBG cord-014597-66vd2mdu 1503 11 CHO CHO NNP cord-014597-66vd2mdu 1503 12 - - HYPH cord-014597-66vd2mdu 1503 13 K1 K1 NNP cord-014597-66vd2mdu 1503 14 cells cell NNS cord-014597-66vd2mdu 1503 15 due due JJ cord-014597-66vd2mdu 1503 16 to to IN cord-014597-66vd2mdu 1503 17 their -PRON- PRP$ cord-014597-66vd2mdu 1503 18 widespread widespread JJ cord-014597-66vd2mdu 1503 19 use use NN cord-014597-66vd2mdu 1503 20 in in IN cord-014597-66vd2mdu 1503 21 industrial industrial JJ cord-014597-66vd2mdu 1503 22 antibody antibody NN cord-014597-66vd2mdu 1503 23 production production NN cord-014597-66vd2mdu 1503 24 . . . cord-014597-66vd2mdu 1504 1 Successful successful JJ cord-014597-66vd2mdu 1504 2 media medium NNS cord-014597-66vd2mdu 1504 3 candidates candidate NNS cord-014597-66vd2mdu 1504 4 were be VBD cord-014597-66vd2mdu 1504 5 subsequently subsequently RB cord-014597-66vd2mdu 1504 6 screened screen VBN cord-014597-66vd2mdu 1504 7 using use VBG cord-014597-66vd2mdu 1504 8 additional additional JJ cord-014597-66vd2mdu 1504 9 CHO CHO NNP cord-014597-66vd2mdu 1504 10 cell cell NN cord-014597-66vd2mdu 1504 11 lines line NNS cord-014597-66vd2mdu 1504 12 . . . cord-014597-66vd2mdu 1505 1 Table table NN cord-014597-66vd2mdu 1505 2 1 1 CD cord-014597-66vd2mdu 1505 3 ) ) -RRB- cord-014597-66vd2mdu 1505 4 . . . cord-014597-66vd2mdu 1506 1 The the DT cord-014597-66vd2mdu 1506 2 K1-SFMII K1-SFMII NNP cord-014597-66vd2mdu 1506 3 - - HYPH cord-014597-66vd2mdu 1506 4 CM CM NNP cord-014597-66vd2mdu 1506 5 product product NN cord-014597-66vd2mdu 1506 6 improved improve VBN cord-014597-66vd2mdu 1506 7 cell cell NN cord-014597-66vd2mdu 1506 8 cloning cloning NN cord-014597-66vd2mdu 1506 9 efficiency efficiency NN cord-014597-66vd2mdu 1506 10 for for IN cord-014597-66vd2mdu 1506 11 DG44 DG44 NNP cord-014597-66vd2mdu 1506 12 cells cell NNS cord-014597-66vd2mdu 1506 13 ( ( -LRB- cord-014597-66vd2mdu 1506 14 avg avg NN cord-014597-66vd2mdu 1506 15 . . . cord-014597-66vd2mdu 1507 1 increase>1.5-fold increase>1.5-fold NNP cord-014597-66vd2mdu 1507 2 ) ) -RRB- cord-014597-66vd2mdu 1507 3 and and CC cord-014597-66vd2mdu 1507 4 CHO CHO NNP cord-014597-66vd2mdu 1507 5 - - HYPH cord-014597-66vd2mdu 1507 6 S S NNP cord-014597-66vd2mdu 1507 7 cells cell NNS cord-014597-66vd2mdu 1507 8 ( ( -LRB- cord-014597-66vd2mdu 1507 9 avg avg NNP cord-014597-66vd2mdu 1507 10 . . NNP cord-014597-66vd2mdu 1507 11 increase>3-fold increase>3-fold CD cord-014597-66vd2mdu 1507 12 ) ) -RRB- cord-014597-66vd2mdu 1508 1 ( ( -LRB- cord-014597-66vd2mdu 1508 2 Fig Fig NNP cord-014597-66vd2mdu 1508 3 . . . cord-014597-66vd2mdu 1509 1 1 1 LS cord-014597-66vd2mdu 1509 2 ) ) -RRB- cord-014597-66vd2mdu 1509 3 and and CC cord-014597-66vd2mdu 1509 4 also also RB cord-014597-66vd2mdu 1509 5 the the DT cord-014597-66vd2mdu 1509 6 adherent adherent JJ cord-014597-66vd2mdu 1509 7 CHO CHO NNP cord-014597-66vd2mdu 1509 8 - - HYPH cord-014597-66vd2mdu 1509 9 K1 K1 NNP cord-014597-66vd2mdu 1509 10 cell cell NN cord-014597-66vd2mdu 1509 11 line line NN cord-014597-66vd2mdu 1509 12 growing grow VBG cord-014597-66vd2mdu 1509 13 in in IN cord-014597-66vd2mdu 1509 14 ATCC ATCC NNP cord-014597-66vd2mdu 1509 15 +5%FBS +5%fbs NN cord-014597-66vd2mdu 1509 16 . . . cord-014597-66vd2mdu 1510 1 The the DT cord-014597-66vd2mdu 1510 2 ability ability NN cord-014597-66vd2mdu 1510 3 of of IN cord-014597-66vd2mdu 1510 4 conditioned condition VBN cord-014597-66vd2mdu 1510 5 media medium NNS cord-014597-66vd2mdu 1510 6 to to TO cord-014597-66vd2mdu 1510 7 support support VB cord-014597-66vd2mdu 1510 8 CHO CHO NNP cord-014597-66vd2mdu 1510 9 growth growth NN cord-014597-66vd2mdu 1510 10 in in IN cord-014597-66vd2mdu 1510 11 limiting limit VBG cord-014597-66vd2mdu 1510 12 - - HYPH cord-014597-66vd2mdu 1510 13 dilution dilution NN cord-014597-66vd2mdu 1510 14 conditions condition NNS cord-014597-66vd2mdu 1510 15 ( ( -LRB- cord-014597-66vd2mdu 1510 16 1 1 CD cord-014597-66vd2mdu 1510 17 , , , cord-014597-66vd2mdu 1510 18 6 6 CD cord-014597-66vd2mdu 1510 19 and and CC cord-014597-66vd2mdu 1510 20 10 10 CD cord-014597-66vd2mdu 1510 21 cells cell NNS cord-014597-66vd2mdu 1510 22 / / SYM cord-014597-66vd2mdu 1510 23 ml ml NN cord-014597-66vd2mdu 1510 24 ) ) -RRB- cord-014597-66vd2mdu 1510 25 was be VBD cord-014597-66vd2mdu 1510 26 investigated investigate VBN cord-014597-66vd2mdu 1510 27 . . . cord-014597-66vd2mdu 1511 1 From from IN cord-014597-66vd2mdu 1511 2 a a DT cord-014597-66vd2mdu 1511 3 range range NN cord-014597-66vd2mdu 1511 4 of of IN cord-014597-66vd2mdu 1511 5 nine nine CD cord-014597-66vd2mdu 1511 6 conditioned condition VBN cord-014597-66vd2mdu 1511 7 media medium NNS cord-014597-66vd2mdu 1511 8 samples sample NNS cord-014597-66vd2mdu 1511 9 ; ; : cord-014597-66vd2mdu 1511 10 four four CD cord-014597-66vd2mdu 1511 11 compelling compelling JJ cord-014597-66vd2mdu 1511 12 products product NNS cord-014597-66vd2mdu 1511 13 have have VBP cord-014597-66vd2mdu 1511 14 been be VBN cord-014597-66vd2mdu 1511 15 identified identify VBN cord-014597-66vd2mdu 1511 16 which which WDT cord-014597-66vd2mdu 1511 17 improve improve VBP cord-014597-66vd2mdu 1511 18 low low JJ cord-014597-66vd2mdu 1511 19 - - HYPH cord-014597-66vd2mdu 1511 20 cell cell NN cord-014597-66vd2mdu 1511 21 density density NN cord-014597-66vd2mdu 1511 22 growth growth NN cord-014597-66vd2mdu 1511 23 of of IN cord-014597-66vd2mdu 1511 24 CHO CHO NNP cord-014597-66vd2mdu 1511 25 - - HYPH cord-014597-66vd2mdu 1511 26 K1 K1 NNP cord-014597-66vd2mdu 1511 27 cells cell NNS cord-014597-66vd2mdu 1511 28 , , , cord-014597-66vd2mdu 1511 29 compared compare VBN cord-014597-66vd2mdu 1511 30 to to IN cord-014597-66vd2mdu 1511 31 SFM SFM NNP cord-014597-66vd2mdu 1511 32 - - HYPH cord-014597-66vd2mdu 1511 33 II II NNP cord-014597-66vd2mdu 1511 34 control control NN cord-014597-66vd2mdu 1511 35 media medium NNS cord-014597-66vd2mdu 1511 36 . . . cord-014597-66vd2mdu 1512 1 We -PRON- PRP cord-014597-66vd2mdu 1512 2 feel feel VBP cord-014597-66vd2mdu 1512 3 that that IN cord-014597-66vd2mdu 1512 4 these these DT cord-014597-66vd2mdu 1512 5 early early JJ cord-014597-66vd2mdu 1512 6 - - HYPH cord-014597-66vd2mdu 1512 7 stage stage NN cord-014597-66vd2mdu 1512 8 conditioned condition VBN cord-014597-66vd2mdu 1512 9 media medium NNS cord-014597-66vd2mdu 1512 10 products product NNS cord-014597-66vd2mdu 1512 11 may may MD cord-014597-66vd2mdu 1512 12 increase increase VB cord-014597-66vd2mdu 1512 13 cloning clone VBG cord-014597-66vd2mdu 1512 14 efficiencies efficiency NNS cord-014597-66vd2mdu 1512 15 during during IN cord-014597-66vd2mdu 1512 16 upstream upstream JJ cord-014597-66vd2mdu 1512 17 CHO CHO NNP cord-014597-66vd2mdu 1512 18 cell cell NN cord-014597-66vd2mdu 1512 19 line line NN cord-014597-66vd2mdu 1512 20 development development NN cord-014597-66vd2mdu 1512 21 , , , cord-014597-66vd2mdu 1512 22 resulting result VBG cord-014597-66vd2mdu 1512 23 in in IN cord-014597-66vd2mdu 1512 24 financial financial JJ cord-014597-66vd2mdu 1512 25 savings saving NNS cord-014597-66vd2mdu 1512 26 for for IN cord-014597-66vd2mdu 1512 27 industry industry NN cord-014597-66vd2mdu 1512 28 and and CC cord-014597-66vd2mdu 1512 29 increasing increase VBG cord-014597-66vd2mdu 1512 30 the the DT cord-014597-66vd2mdu 1512 31 possibilities possibility NNS cord-014597-66vd2mdu 1512 32 of of IN cord-014597-66vd2mdu 1512 33 identifying identify VBG cord-014597-66vd2mdu 1512 34 particularly particularly RB cord-014597-66vd2mdu 1512 35 highperforming highperforme VBG cord-014597-66vd2mdu 1512 36 transformed transform VBN cord-014597-66vd2mdu 1512 37 clones clone NNS cord-014597-66vd2mdu 1512 38 . . . cord-014597-66vd2mdu 1513 1 12 12 CD cord-014597-66vd2mdu 1513 2 ( ( -LRB- cord-014597-66vd2mdu 1513 3 7):3496 7):3496 CD cord-014597-66vd2mdu 1513 4 - - HYPH cord-014597-66vd2mdu 1513 5 3510 3510 CD cord-014597-66vd2mdu 1513 6 . . . cord-014597-66vd2mdu 1514 1 The the DT cord-014597-66vd2mdu 1514 2 main main JJ cord-014597-66vd2mdu 1514 3 rate rate NN cord-014597-66vd2mdu 1514 4 - - HYPH cord-014597-66vd2mdu 1514 5 limiting limit VBG cord-014597-66vd2mdu 1514 6 step step NN cord-014597-66vd2mdu 1514 7 in in IN cord-014597-66vd2mdu 1514 8 the the DT cord-014597-66vd2mdu 1514 9 upstream upstream JJ cord-014597-66vd2mdu 1514 10 stages stage NNS cord-014597-66vd2mdu 1514 11 of of IN cord-014597-66vd2mdu 1514 12 protein protein NN cord-014597-66vd2mdu 1514 13 biomanufacture biomanufacture NNP cord-014597-66vd2mdu 1514 14 is be VBZ cord-014597-66vd2mdu 1514 15 the the DT cord-014597-66vd2mdu 1514 16 isolation isolation NN cord-014597-66vd2mdu 1514 17 of of IN cord-014597-66vd2mdu 1514 18 stable stable JJ cord-014597-66vd2mdu 1514 19 , , , cord-014597-66vd2mdu 1514 20 high high JJ cord-014597-66vd2mdu 1514 21 producing produce VBG cord-014597-66vd2mdu 1514 22 cell cell NN cord-014597-66vd2mdu 1514 23 clones clone NNS cord-014597-66vd2mdu 1514 24 . . . cord-014597-66vd2mdu 1515 1 Ubiquitous Ubiquitous NNP cord-014597-66vd2mdu 1515 2 Chromatin Chromatin NNP cord-014597-66vd2mdu 1515 3 Opening Opening NNP cord-014597-66vd2mdu 1515 4 Elements Elements NNP cord-014597-66vd2mdu 1515 5 ( ( -LRB- cord-014597-66vd2mdu 1515 6 UCOE UCOE NNP cord-014597-66vd2mdu 1515 7 ® ® POS cord-014597-66vd2mdu 1515 8 s s NN cord-014597-66vd2mdu 1515 9 ) ) -RRB- cord-014597-66vd2mdu 1515 10 consist consist VBP cord-014597-66vd2mdu 1515 11 of of IN cord-014597-66vd2mdu 1515 12 at at RB cord-014597-66vd2mdu 1515 13 least least RBS cord-014597-66vd2mdu 1515 14 one one CD cord-014597-66vd2mdu 1515 15 promoter promoter NN cord-014597-66vd2mdu 1515 16 region region NN cord-014597-66vd2mdu 1515 17 with with IN cord-014597-66vd2mdu 1515 18 associated associated JJ cord-014597-66vd2mdu 1515 19 methylation methylation NN cord-014597-66vd2mdu 1515 20 - - HYPH cord-014597-66vd2mdu 1515 21 free free JJ cord-014597-66vd2mdu 1515 22 CpG CpG NNP cord-014597-66vd2mdu 1515 23 island island NNP cord-014597-66vd2mdu 1515 24 from from IN cord-014597-66vd2mdu 1515 25 housekeeping housekeeping NN cord-014597-66vd2mdu 1515 26 genes gene NNS cord-014597-66vd2mdu 1515 27 ; ; : cord-014597-66vd2mdu 1515 28 they -PRON- PRP cord-014597-66vd2mdu 1515 29 possess possess VBP cord-014597-66vd2mdu 1515 30 a a DT cord-014597-66vd2mdu 1515 31 dominant dominant JJ cord-014597-66vd2mdu 1515 32 chromatin chromatin NN cord-014597-66vd2mdu 1515 33 opening opening NN cord-014597-66vd2mdu 1515 34 capability capability NN cord-014597-66vd2mdu 1515 35 and and CC cord-014597-66vd2mdu 1515 36 thus thus RB cord-014597-66vd2mdu 1515 37 confer confer VB cord-014597-66vd2mdu 1515 38 stable stable JJ cord-014597-66vd2mdu 1515 39 transgene transgene NN cord-014597-66vd2mdu 1515 40 expression expression NN cord-014597-66vd2mdu 1515 41 . . . cord-014597-66vd2mdu 1516 1 UCOE UCOE NNP cord-014597-66vd2mdu 1516 2 ® ® POS cord-014597-66vd2mdu 1516 3 -viral -viral JJ cord-014597-66vd2mdu 1516 4 promoter promoter NN cord-014597-66vd2mdu 1516 5 ( ( -LRB- cord-014597-66vd2mdu 1516 6 e.g. e.g. RB cord-014597-66vd2mdu 1516 7 CMV CMV NNP cord-014597-66vd2mdu 1516 8 ) ) -RRB- cord-014597-66vd2mdu 1516 9 based base VBN cord-014597-66vd2mdu 1516 10 plasmid plasmid NN cord-014597-66vd2mdu 1516 11 vectors vector NNS cord-014597-66vd2mdu 1516 12 markedly markedly RB cord-014597-66vd2mdu 1516 13 reduce reduce VBP cord-014597-66vd2mdu 1516 14 the the DT cord-014597-66vd2mdu 1516 15 time time NN cord-014597-66vd2mdu 1516 16 it -PRON- PRP cord-014597-66vd2mdu 1516 17 takes take VBZ cord-014597-66vd2mdu 1516 18 to to TO cord-014597-66vd2mdu 1516 19 isolate isolate VB cord-014597-66vd2mdu 1516 20 high high JJ cord-014597-66vd2mdu 1516 21 , , , cord-014597-66vd2mdu 1516 22 stably stably RB cord-014597-66vd2mdu 1516 23 producing produce VBG cord-014597-66vd2mdu 1516 24 cell cell NN cord-014597-66vd2mdu 1516 25 clones clone NNS cord-014597-66vd2mdu 1516 26 . . . cord-014597-66vd2mdu 1517 1 Although although IN cord-014597-66vd2mdu 1517 2 some some DT cord-014597-66vd2mdu 1517 3 UCOE UCOE NNP cord-014597-66vd2mdu 1517 4 ® ® POS cord-014597-66vd2mdu 1517 5 -viral -viral JJ cord-014597-66vd2mdu 1517 6 promoter promoter NN cord-014597-66vd2mdu 1517 7 combinations combination NNS cord-014597-66vd2mdu 1517 8 have have VBP cord-014597-66vd2mdu 1517 9 been be VBN cord-014597-66vd2mdu 1517 10 tested test VBN cord-014597-66vd2mdu 1517 11 , , , cord-014597-66vd2mdu 1517 12 they -PRON- PRP cord-014597-66vd2mdu 1517 13 have have VBP cord-014597-66vd2mdu 1517 14 not not RB cord-014597-66vd2mdu 1517 15 been be VBN cord-014597-66vd2mdu 1517 16 thoroughly thoroughly RB cord-014597-66vd2mdu 1517 17 evaluated evaluate VBN cord-014597-66vd2mdu 1517 18 in in IN cord-014597-66vd2mdu 1517 19 Chinese chinese JJ cord-014597-66vd2mdu 1517 20 hamster hamster NN cord-014597-66vd2mdu 1517 21 ovary ovary NN cord-014597-66vd2mdu 1517 22 ( ( -LRB- cord-014597-66vd2mdu 1517 23 CHO CHO NNP cord-014597-66vd2mdu 1517 24 ) ) -RRB- cord-014597-66vd2mdu 1517 25 cells cell NNS cord-014597-66vd2mdu 1517 26 . . . cord-014597-66vd2mdu 1518 1 Plasmid plasmid NN cord-014597-66vd2mdu 1518 2 vectors vector NNS cord-014597-66vd2mdu 1518 3 containing contain VBG cord-014597-66vd2mdu 1518 4 combinations combination NNS cord-014597-66vd2mdu 1518 5 of of IN cord-014597-66vd2mdu 1518 6 either either CC cord-014597-66vd2mdu 1518 7 the the DT cord-014597-66vd2mdu 1518 8 human human NN cord-014597-66vd2mdu 1518 9 HNRPA2B1-CBX3 HNRPA2B1-CBX3 NNP cord-014597-66vd2mdu 1518 10 UCOE UCOE NNP cord-014597-66vd2mdu 1519 1 ® ® . cord-014597-66vd2mdu 1520 1 ( ( -LRB- cord-014597-66vd2mdu 1520 2 A2UCOE A2UCOE NNP cord-014597-66vd2mdu 1520 3 ® ® , cord-014597-66vd2mdu 1520 4 ) ) -RRB- cord-014597-66vd2mdu 1520 5 or or CC cord-014597-66vd2mdu 1520 6 murine murine JJ cord-014597-66vd2mdu 1520 7 Rps3 rps3 NN cord-014597-66vd2mdu 1520 8 UCOE UCOE NNP cord-014597-66vd2mdu 1521 1 ® ® , cord-014597-66vd2mdu 1521 2 linked link VBN cord-014597-66vd2mdu 1521 3 to to IN cord-014597-66vd2mdu 1521 4 different different JJ cord-014597-66vd2mdu 1521 5 viral viral JJ cord-014597-66vd2mdu 1521 6 promoters promoter NNS cord-014597-66vd2mdu 1521 7 ( ( -LRB- cord-014597-66vd2mdu 1521 8 hCMV hcmv RB cord-014597-66vd2mdu 1521 9 , , , cord-014597-66vd2mdu 1521 10 gpCMV gpcmv NN cord-014597-66vd2mdu 1521 11 , , , cord-014597-66vd2mdu 1521 12 SFFV SFFV NNP cord-014597-66vd2mdu 1521 13 ) ) -RRB- cord-014597-66vd2mdu 1521 14 driving drive VBG cord-014597-66vd2mdu 1521 15 expression expression NN cord-014597-66vd2mdu 1521 16 of of IN cord-014597-66vd2mdu 1521 17 an an DT cord-014597-66vd2mdu 1521 18 eGFP egfp JJ cord-014597-66vd2mdu 1521 19 reporter reporter NN cord-014597-66vd2mdu 1521 20 gene gene NN cord-014597-66vd2mdu 1521 21 were be VBD cord-014597-66vd2mdu 1521 22 functionally functionally RB cord-014597-66vd2mdu 1521 23 analysed analyse VBN cord-014597-66vd2mdu 1521 24 by by IN cord-014597-66vd2mdu 1521 25 stable stable JJ cord-014597-66vd2mdu 1521 26 transfection transfection NN cord-014597-66vd2mdu 1521 27 into into IN cord-014597-66vd2mdu 1521 28 CHO CHO NNP cord-014597-66vd2mdu 1521 29 - - HYPH cord-014597-66vd2mdu 1521 30 K1 K1 NNP cord-014597-66vd2mdu 1521 31 cells cell NNS cord-014597-66vd2mdu 1521 32 and and CC cord-014597-66vd2mdu 1521 33 expression expression NN cord-014597-66vd2mdu 1521 34 analysed analyse VBN cord-014597-66vd2mdu 1521 35 by by IN cord-014597-66vd2mdu 1521 36 flow flow NN cord-014597-66vd2mdu 1521 37 cytometry cytometry NN cord-014597-66vd2mdu 1521 38 and and CC cord-014597-66vd2mdu 1521 39 qPCR qpcr NN cord-014597-66vd2mdu 1521 40 to to TO cord-014597-66vd2mdu 1521 41 determine determine VB cord-014597-66vd2mdu 1521 42 vector vector NN cord-014597-66vd2mdu 1521 43 copy copy NN cord-014597-66vd2mdu 1521 44 number number NN cord-014597-66vd2mdu 1521 45 . . . cord-014597-66vd2mdu 1522 1 The the DT cord-014597-66vd2mdu 1522 2 results result NNS cord-014597-66vd2mdu 1522 3 at at IN cord-014597-66vd2mdu 1522 4 21 21 CD cord-014597-66vd2mdu 1522 5 days day NNS cord-014597-66vd2mdu 1522 6 post post NN cord-014597-66vd2mdu 1522 7 - - JJ cord-014597-66vd2mdu 1522 8 transfection transfection JJ cord-014597-66vd2mdu 1522 9 and and CC cord-014597-66vd2mdu 1522 10 selection selection NN cord-014597-66vd2mdu 1522 11 clearly clearly RB cord-014597-66vd2mdu 1522 12 indicate indicate VBP cord-014597-66vd2mdu 1522 13 that that IN cord-014597-66vd2mdu 1522 14 the the DT cord-014597-66vd2mdu 1522 15 Rps3 Rps3 NNP cord-014597-66vd2mdu 1522 16 UCOE UCOE NNP cord-014597-66vd2mdu 1523 1 ® ® . cord-014597-66vd2mdu 1524 1 -gpCMV -gpCMV . cord-014597-66vd2mdu 1525 1 and and CC cord-014597-66vd2mdu 1525 2 -hCMV -hcmv CD cord-014597-66vd2mdu 1525 3 combinations combination NNS cord-014597-66vd2mdu 1525 4 give give VBP cord-014597-66vd2mdu 1525 5 the the DT cord-014597-66vd2mdu 1525 6 highest high JJS cord-014597-66vd2mdu 1525 7 transgene transgene JJ cord-014597-66vd2mdu 1525 8 expression expression NN cord-014597-66vd2mdu 1525 9 as as IN cord-014597-66vd2mdu 1525 10 shown show VBN cord-014597-66vd2mdu 1525 11 in in IN cord-014597-66vd2mdu 1525 12 Fig Fig NNP cord-014597-66vd2mdu 1525 13 . . . cord-014597-66vd2mdu 1526 1 1 1 LS cord-014597-66vd2mdu 1526 2 . . . cord-014597-66vd2mdu 1527 1 The the DT cord-014597-66vd2mdu 1527 2 A2UCOE a2ucoe NN cord-014597-66vd2mdu 1527 3 ® ® VBP cord-014597-66vd2mdu 1527 4 -hCMV -hcmv XX cord-014597-66vd2mdu 1527 5 / / NFP cord-014597-66vd2mdu 1527 6 gpCMV gpcmv NN cord-014597-66vd2mdu 1527 7 constructs construct NNS cord-014597-66vd2mdu 1527 8 were be VBD cord-014597-66vd2mdu 1527 9 the the DT cord-014597-66vd2mdu 1527 10 next next JJ cord-014597-66vd2mdu 1527 11 efficacious efficacious JJ cord-014597-66vd2mdu 1527 12 but but CC cord-014597-66vd2mdu 1527 13 2-fold 2-fold CD cord-014597-66vd2mdu 1527 14 lower low JJR cord-014597-66vd2mdu 1527 15 than than IN cord-014597-66vd2mdu 1527 16 the the DT cord-014597-66vd2mdu 1527 17 Rps3 Rps3 NNP cord-014597-66vd2mdu 1527 18 UCOE UCOE NNP cord-014597-66vd2mdu 1528 1 ® ® NNP cord-014597-66vd2mdu 1528 2 vectors vector NNS cord-014597-66vd2mdu 1528 3 . . . cord-014597-66vd2mdu 1529 1 The the DT cord-014597-66vd2mdu 1529 2 SFFV SFFV NNP cord-014597-66vd2mdu 1529 3 promoter promoter NN cord-014597-66vd2mdu 1529 4 linked link VBN cord-014597-66vd2mdu 1529 5 with with IN cord-014597-66vd2mdu 1529 6 either either DT cord-014597-66vd2mdu 1529 7 of of IN cord-014597-66vd2mdu 1529 8 the the DT cord-014597-66vd2mdu 1529 9 two two CD cord-014597-66vd2mdu 1529 10 UCOE UCOE NNP cord-014597-66vd2mdu 1530 1 ® ® NNP cord-014597-66vd2mdu 1530 2 s s NNP cord-014597-66vd2mdu 1530 3 was be VBD cord-014597-66vd2mdu 1530 4 the the DT cord-014597-66vd2mdu 1530 5 least least JJS cord-014597-66vd2mdu 1530 6 effective effective JJ cord-014597-66vd2mdu 1530 7 with with IN cord-014597-66vd2mdu 1530 8 expression expression NN cord-014597-66vd2mdu 1530 9 levels level NNS cord-014597-66vd2mdu 1531 1 17-fold 17-fold JJ cord-014597-66vd2mdu 1531 2 lower low JJR cord-014597-66vd2mdu 1531 3 than than IN cord-014597-66vd2mdu 1531 4 the the DT cord-014597-66vd2mdu 1531 5 Rps3-CMV rps3-cmv NN cord-014597-66vd2mdu 1531 6 constructs construct NNS cord-014597-66vd2mdu 1531 7 . . . cord-014597-66vd2mdu 1532 1 The the DT cord-014597-66vd2mdu 1532 2 Rps3 Rps3 NNP cord-014597-66vd2mdu 1532 3 UCOE UCOE NNP cord-014597-66vd2mdu 1532 4 ® ® . cord-014597-66vd2mdu 1533 1 -gpCMV -gpCMV : cord-014597-66vd2mdu 1533 2 / / SYM cord-014597-66vd2mdu 1533 3 hCMV hcmv NN cord-014597-66vd2mdu 1533 4 constructs construct NNS cord-014597-66vd2mdu 1533 5 are be VBP cord-014597-66vd2mdu 1533 6 now now RB cord-014597-66vd2mdu 1533 7 being be VBG cord-014597-66vd2mdu 1533 8 further further RB cord-014597-66vd2mdu 1533 9 modified modify VBN cord-014597-66vd2mdu 1533 10 to to TO cord-014597-66vd2mdu 1533 11 include include VB cord-014597-66vd2mdu 1533 12 elements element NNS cord-014597-66vd2mdu 1533 13 that that WDT cord-014597-66vd2mdu 1533 14 will will MD cord-014597-66vd2mdu 1533 15 provide provide VB cord-014597-66vd2mdu 1533 16 optimal optimal JJ cord-014597-66vd2mdu 1533 17 post post JJ cord-014597-66vd2mdu 1533 18 - - JJ cord-014597-66vd2mdu 1533 19 transcriptional transcriptional JJ cord-014597-66vd2mdu 1533 20 pre pre JJ cord-014597-66vd2mdu 1533 21 - - JJ cord-014597-66vd2mdu 1533 22 mRNA mrna JJ cord-014597-66vd2mdu 1533 23 processing processing NN cord-014597-66vd2mdu 1533 24 ( ( -LRB- cord-014597-66vd2mdu 1533 25 splicing splicing NN cord-014597-66vd2mdu 1533 26 , , , cord-014597-66vd2mdu 1533 27 polyadenylation polyadenylation NN cord-014597-66vd2mdu 1533 28 , , , cord-014597-66vd2mdu 1533 29 transcription transcription NN cord-014597-66vd2mdu 1533 30 termination termination NN cord-014597-66vd2mdu 1533 31 , , , cord-014597-66vd2mdu 1533 32 mRNA mrna NN cord-014597-66vd2mdu 1533 33 stability stability NN cord-014597-66vd2mdu 1533 34 ) ) -RRB- cord-014597-66vd2mdu 1533 35 thereby thereby RB cord-014597-66vd2mdu 1533 36 maximising maximise VBG cord-014597-66vd2mdu 1533 37 stable stable JJ cord-014597-66vd2mdu 1533 38 cytoplasmic cytoplasmic JJ cord-014597-66vd2mdu 1533 39 transgene transgene NN cord-014597-66vd2mdu 1533 40 mRNA mrna NN cord-014597-66vd2mdu 1533 41 levels level NNS cord-014597-66vd2mdu 1533 42 and and CC cord-014597-66vd2mdu 1533 43 protein protein NN cord-014597-66vd2mdu 1533 44 production production NN cord-014597-66vd2mdu 1533 45 . . . cord-014597-66vd2mdu 1534 1 In in IN cord-014597-66vd2mdu 1534 2 the the DT cord-014597-66vd2mdu 1534 3 last last JJ cord-014597-66vd2mdu 1534 4 20 20 CD cord-014597-66vd2mdu 1534 5 years year NNS cord-014597-66vd2mdu 1534 6 , , , cord-014597-66vd2mdu 1534 7 growing grow VBG cord-014597-66vd2mdu 1534 8 number number NN cord-014597-66vd2mdu 1534 9 of of IN cord-014597-66vd2mdu 1534 10 innovator innovator NN cord-014597-66vd2mdu 1534 11 biologics biologic NNS cord-014597-66vd2mdu 1534 12 and and CC cord-014597-66vd2mdu 1534 13 biosimilars biosimilar NNS cord-014597-66vd2mdu 1534 14 have have VBP cord-014597-66vd2mdu 1534 15 formed form VBN cord-014597-66vd2mdu 1534 16 a a DT cord-014597-66vd2mdu 1534 17 competitive competitive JJ cord-014597-66vd2mdu 1534 18 environment environment NN cord-014597-66vd2mdu 1534 19 , , , cord-014597-66vd2mdu 1534 20 where where WRB cord-014597-66vd2mdu 1534 21 speed speed NN cord-014597-66vd2mdu 1534 22 and and CC cord-014597-66vd2mdu 1534 23 efficiency efficiency NN cord-014597-66vd2mdu 1534 24 of of IN cord-014597-66vd2mdu 1534 25 generating generate VBG cord-014597-66vd2mdu 1534 26 robust robust JJ cord-014597-66vd2mdu 1534 27 and and CC cord-014597-66vd2mdu 1534 28 highly highly RB cord-014597-66vd2mdu 1534 29 productive productive JJ cord-014597-66vd2mdu 1534 30 cell cell NN cord-014597-66vd2mdu 1534 31 lines line NNS cord-014597-66vd2mdu 1534 32 needs need VBZ cord-014597-66vd2mdu 1534 33 to to TO cord-014597-66vd2mdu 1534 34 be be VB cord-014597-66vd2mdu 1534 35 improved improve VBN cord-014597-66vd2mdu 1534 36 continuously continuously RB cord-014597-66vd2mdu 1534 37 . . . cord-014597-66vd2mdu 1535 1 Through through IN cord-014597-66vd2mdu 1535 2 various various JJ cord-014597-66vd2mdu 1535 3 advances advance NNS cord-014597-66vd2mdu 1535 4 , , , cord-014597-66vd2mdu 1535 5 especially especially RB cord-014597-66vd2mdu 1535 6 in in IN cord-014597-66vd2mdu 1535 7 media medium NNS cord-014597-66vd2mdu 1535 8 development development NN cord-014597-66vd2mdu 1535 9 and and CC cord-014597-66vd2mdu 1535 10 process process NN cord-014597-66vd2mdu 1535 11 optimization optimization NN cord-014597-66vd2mdu 1535 12 , , , cord-014597-66vd2mdu 1535 13 product product NN cord-014597-66vd2mdu 1535 14 titers titer NNS cord-014597-66vd2mdu 1535 15 as as RB cord-014597-66vd2mdu 1535 16 high high JJ cord-014597-66vd2mdu 1535 17 as as IN cord-014597-66vd2mdu 1535 18 10 10 CD cord-014597-66vd2mdu 1535 19 g g NN cord-014597-66vd2mdu 1535 20 / / SYM cord-014597-66vd2mdu 1535 21 L L NNP cord-014597-66vd2mdu 1535 22 were be VBD cord-014597-66vd2mdu 1535 23 achieved achieve VBN cord-014597-66vd2mdu 1535 24 in in IN cord-014597-66vd2mdu 1535 25 the the DT cord-014597-66vd2mdu 1535 26 pharmaceutical pharmaceutical NN cord-014597-66vd2mdu 1535 27 industry industry NN cord-014597-66vd2mdu 1535 28 ( ( -LRB- cord-014597-66vd2mdu 1535 29 Kim Kim NNP cord-014597-66vd2mdu 1535 30 et et NNP cord-014597-66vd2mdu 1535 31 al al NNP cord-014597-66vd2mdu 1535 32 . . NNP cord-014597-66vd2mdu 1535 33 , , , cord-014597-66vd2mdu 1535 34 2012 2012 CD cord-014597-66vd2mdu 1535 35 ) ) -RRB- cord-014597-66vd2mdu 1535 36 for for IN cord-014597-66vd2mdu 1535 37 standard standard JJ cord-014597-66vd2mdu 1535 38 products product NNS cord-014597-66vd2mdu 1535 39 such such JJ cord-014597-66vd2mdu 1535 40 as as IN cord-014597-66vd2mdu 1535 41 monoclonal monoclonal JJ cord-014597-66vd2mdu 1535 42 antibodies antibody NNS cord-014597-66vd2mdu 1535 43 . . . cord-014597-66vd2mdu 1536 1 Nevertheless nevertheless RB cord-014597-66vd2mdu 1536 2 , , , cord-014597-66vd2mdu 1536 3 other other JJ cord-014597-66vd2mdu 1536 4 proteins protein NNS cord-014597-66vd2mdu 1537 1 e.g. e.g. IN cord-014597-66vd2mdu 1537 2 bispecific bispecific NNP cord-014597-66vd2mdu 1537 3 antibodies antibody NNS cord-014597-66vd2mdu 1537 4 , , , cord-014597-66vd2mdu 1537 5 Fc Fc NNP cord-014597-66vd2mdu 1537 6 - - HYPH cord-014597-66vd2mdu 1537 7 fusion fusion NN cord-014597-66vd2mdu 1537 8 proteins protein NNS cord-014597-66vd2mdu 1537 9 or or CC cord-014597-66vd2mdu 1537 10 Fab fab JJ cord-014597-66vd2mdu 1537 11 - - HYPH cord-014597-66vd2mdu 1537 12 related relate VBN cord-014597-66vd2mdu 1537 13 products product NNS cord-014597-66vd2mdu 1537 14 are be VBP cord-014597-66vd2mdu 1537 15 difficult difficult JJ cord-014597-66vd2mdu 1537 16 - - HYPH cord-014597-66vd2mdu 1537 17 to to TO cord-014597-66vd2mdu 1537 18 - - HYPH cord-014597-66vd2mdu 1537 19 express express VB cord-014597-66vd2mdu 1537 20 ( ( -LRB- cord-014597-66vd2mdu 1537 21 DTE DTE NNP cord-014597-66vd2mdu 1537 22 ) ) -RRB- cord-014597-66vd2mdu 1537 23 in in IN cord-014597-66vd2mdu 1537 24 Chinese chinese JJ cord-014597-66vd2mdu 1537 25 Hamster Hamster NNP cord-014597-66vd2mdu 1537 26 Ovary Ovary NNP cord-014597-66vd2mdu 1537 27 ( ( -LRB- cord-014597-66vd2mdu 1537 28 CHO CHO NNP cord-014597-66vd2mdu 1537 29 ) ) -RRB- cord-014597-66vd2mdu 1537 30 and and CC cord-014597-66vd2mdu 1537 31 may may MD cord-014597-66vd2mdu 1537 32 result result VB cord-014597-66vd2mdu 1537 33 in in IN cord-014597-66vd2mdu 1537 34 delays delay NNS cord-014597-66vd2mdu 1537 35 or or CC cord-014597-66vd2mdu 1537 36 even even RB cord-014597-66vd2mdu 1537 37 in in IN cord-014597-66vd2mdu 1537 38 termination termination NN cord-014597-66vd2mdu 1537 39 of of IN cord-014597-66vd2mdu 1537 40 the the DT cord-014597-66vd2mdu 1537 41 cell cell NN cord-014597-66vd2mdu 1537 42 line line NN cord-014597-66vd2mdu 1537 43 development development NN cord-014597-66vd2mdu 1537 44 process process NN cord-014597-66vd2mdu 1537 45 . . . cord-014597-66vd2mdu 1538 1 We -PRON- PRP cord-014597-66vd2mdu 1538 2 developed develop VBD cord-014597-66vd2mdu 1538 3 a a DT cord-014597-66vd2mdu 1538 4 new new JJ cord-014597-66vd2mdu 1538 5 robust robust JJ cord-014597-66vd2mdu 1538 6 pool pool NN cord-014597-66vd2mdu 1538 7 generation generation NN cord-014597-66vd2mdu 1538 8 approach approach NN cord-014597-66vd2mdu 1538 9 ( ( -LRB- cord-014597-66vd2mdu 1538 10 CLD CLD NNP cord-014597-66vd2mdu 1538 11 2.0 2.0 CD cord-014597-66vd2mdu 1538 12 ) ) -RRB- cord-014597-66vd2mdu 1538 13 addressing address VBG cord-014597-66vd2mdu 1538 14 both both DT cord-014597-66vd2mdu 1538 15 , , , cord-014597-66vd2mdu 1538 16 easy easy JJ cord-014597-66vd2mdu 1538 17 - - HYPH cord-014597-66vd2mdu 1538 18 and and CC cord-014597-66vd2mdu 1538 19 difficult difficult JJ cord-014597-66vd2mdu 1538 20 - - HYPH cord-014597-66vd2mdu 1538 21 to to TO cord-014597-66vd2mdu 1538 22 - - HYPH cord-014597-66vd2mdu 1538 23 express express NN cord-014597-66vd2mdu 1538 24 molecules molecule NNS cord-014597-66vd2mdu 1538 25 , , , cord-014597-66vd2mdu 1538 26 while while IN cord-014597-66vd2mdu 1538 27 reducing reduce VBG cord-014597-66vd2mdu 1538 28 timelines timeline NNS cord-014597-66vd2mdu 1538 29 down down RB cord-014597-66vd2mdu 1538 30 to to IN cord-014597-66vd2mdu 1538 31 5 5 CD cord-014597-66vd2mdu 1538 32 months month NNS cord-014597-66vd2mdu 1538 33 ( ( -LRB- cord-014597-66vd2mdu 1538 34 CLD CLD NNP cord-014597-66vd2mdu 1538 35 standard standard NN cord-014597-66vd2mdu 1538 36 = = SYM cord-014597-66vd2mdu 1538 37 6 6 CD cord-014597-66vd2mdu 1538 38 months month NNS cord-014597-66vd2mdu 1538 39 ) ) -RRB- cord-014597-66vd2mdu 1538 40 , , , cord-014597-66vd2mdu 1538 41 improving improve VBG cord-014597-66vd2mdu 1538 42 reliability reliability NN cord-014597-66vd2mdu 1538 43 of of IN cord-014597-66vd2mdu 1538 44 cell cell NN cord-014597-66vd2mdu 1538 45 line line NN cord-014597-66vd2mdu 1538 46 development development NN cord-014597-66vd2mdu 1538 47 as as RB cord-014597-66vd2mdu 1538 48 well well RB cord-014597-66vd2mdu 1538 49 as as IN cord-014597-66vd2mdu 1538 50 clearly clearly RB cord-014597-66vd2mdu 1538 51 increasing increase VBG cord-014597-66vd2mdu 1538 52 obtained obtain VBN cord-014597-66vd2mdu 1538 53 titers titer NNS cord-014597-66vd2mdu 1538 54 . . . cord-014597-66vd2mdu 1539 1 In in IN cord-014597-66vd2mdu 1539 2 order order NN cord-014597-66vd2mdu 1539 3 to to TO cord-014597-66vd2mdu 1539 4 create create VB cord-014597-66vd2mdu 1539 5 stable stable JJ cord-014597-66vd2mdu 1539 6 cell cell NN cord-014597-66vd2mdu 1539 7 lines line NNS cord-014597-66vd2mdu 1539 8 , , , cord-014597-66vd2mdu 1539 9 we -PRON- PRP cord-014597-66vd2mdu 1539 10 transfected transfecte VBD cord-014597-66vd2mdu 1539 11 our -PRON- PRP$ cord-014597-66vd2mdu 1539 12 CHO CHO NNP cord-014597-66vd2mdu 1539 13 DG44 DG44 NNP cord-014597-66vd2mdu 1539 14 host host NN cord-014597-66vd2mdu 1539 15 cells cell NNS cord-014597-66vd2mdu 1539 16 by by IN cord-014597-66vd2mdu 1539 17 electroporation electroporation NN cord-014597-66vd2mdu 1539 18 . . . cord-014597-66vd2mdu 1540 1 Cells cell NNS cord-014597-66vd2mdu 1540 2 processed process VBN cord-014597-66vd2mdu 1540 3 using use VBG cord-014597-66vd2mdu 1540 4 the the DT cord-014597-66vd2mdu 1540 5 standard standard JJ cord-014597-66vd2mdu 1540 6 approach approach NN cord-014597-66vd2mdu 1540 7 were be VBD cord-014597-66vd2mdu 1540 8 cultivated cultivate VBN cord-014597-66vd2mdu 1540 9 in in IN cord-014597-66vd2mdu 1540 10 selective selective JJ cord-014597-66vd2mdu 1540 11 medium medium NN cord-014597-66vd2mdu 1540 12 or or CC cord-014597-66vd2mdu 1540 13 medium medium NN cord-014597-66vd2mdu 1540 14 containing contain VBG cord-014597-66vd2mdu 1540 15 additional additional JJ cord-014597-66vd2mdu 1540 16 2.5 2.5 CD cord-014597-66vd2mdu 1540 17 nM nM NNP cord-014597-66vd2mdu 1540 18 methotrexate methotrexate NNP cord-014597-66vd2mdu 1540 19 ( ( -LRB- cord-014597-66vd2mdu 1540 20 MTX MTX NNP cord-014597-66vd2mdu 1540 21 ) ) -RRB- cord-014597-66vd2mdu 1540 22 for for IN cord-014597-66vd2mdu 1540 23 three three CD cord-014597-66vd2mdu 1540 24 weeks week NNS cord-014597-66vd2mdu 1540 25 . . . cord-014597-66vd2mdu 1541 1 After after IN cord-014597-66vd2mdu 1541 2 an an DT cord-014597-66vd2mdu 1541 3 amplification amplification NN cord-014597-66vd2mdu 1541 4 step step NN cord-014597-66vd2mdu 1541 5 with with IN cord-014597-66vd2mdu 1541 6 30 30 CD cord-014597-66vd2mdu 1541 7 nM nm NN cord-014597-66vd2mdu 1541 8 MTX MTX NNP cord-014597-66vd2mdu 1541 9 for for IN cord-014597-66vd2mdu 1541 10 three three CD cord-014597-66vd2mdu 1541 11 weeks week NNS cord-014597-66vd2mdu 1541 12 , , , cord-014597-66vd2mdu 1541 13 stable stable JJ cord-014597-66vd2mdu 1541 14 individual individual JJ cord-014597-66vd2mdu 1541 15 cell cell NN cord-014597-66vd2mdu 1541 16 pools pool NNS cord-014597-66vd2mdu 1541 17 were be VBD cord-014597-66vd2mdu 1541 18 expanded expand VBN cord-014597-66vd2mdu 1541 19 and and CC cord-014597-66vd2mdu 1541 20 clones clone NNS cord-014597-66vd2mdu 1541 21 were be VBD cord-014597-66vd2mdu 1541 22 generated generate VBN cord-014597-66vd2mdu 1541 23 by by IN cord-014597-66vd2mdu 1541 24 FACS FACS NNP cord-014597-66vd2mdu 1541 25 - - HYPH cord-014597-66vd2mdu 1541 26 sorting sorting NN cord-014597-66vd2mdu 1541 27 . . . cord-014597-66vd2mdu 1542 1 Clones clone NNS cord-014597-66vd2mdu 1542 2 were be VBD cord-014597-66vd2mdu 1542 3 analyzed analyze VBN cord-014597-66vd2mdu 1542 4 for for IN cord-014597-66vd2mdu 1542 5 growth growth NN cord-014597-66vd2mdu 1542 6 performance performance NN cord-014597-66vd2mdu 1542 7 and and CC cord-014597-66vd2mdu 1542 8 product product NN cord-014597-66vd2mdu 1542 9 concentration concentration NN cord-014597-66vd2mdu 1542 10 in in IN cord-014597-66vd2mdu 1542 11 fed fed NNP cord-014597-66vd2mdu 1542 12 - - HYPH cord-014597-66vd2mdu 1542 13 batch batch NN cord-014597-66vd2mdu 1542 14 studies study NNS cord-014597-66vd2mdu 1542 15 . . . cord-014597-66vd2mdu 1543 1 In in IN cord-014597-66vd2mdu 1543 2 our -PRON- PRP$ cord-014597-66vd2mdu 1543 3 new new JJ cord-014597-66vd2mdu 1543 4 CLD CLD NNP cord-014597-66vd2mdu 1543 5 2.0 2.0 CD cord-014597-66vd2mdu 1543 6 approach approach NN cord-014597-66vd2mdu 1543 7 , , , cord-014597-66vd2mdu 1543 8 we -PRON- PRP cord-014597-66vd2mdu 1543 9 increased increase VBD cord-014597-66vd2mdu 1543 10 MTX MTX NNP cord-014597-66vd2mdu 1543 11 concentrations concentration NNS cord-014597-66vd2mdu 1543 12 ( ( -LRB- cord-014597-66vd2mdu 1543 13 2.5 2.5 CD cord-014597-66vd2mdu 1543 14 nM nm NN cord-014597-66vd2mdu 1543 15 , , , cord-014597-66vd2mdu 1543 16 5 5 CD cord-014597-66vd2mdu 1543 17 nM nm NN cord-014597-66vd2mdu 1543 18 and and CC cord-014597-66vd2mdu 1543 19 10 10 CD cord-014597-66vd2mdu 1543 20 nM nm NN cord-014597-66vd2mdu 1543 21 MTX MTX NNP cord-014597-66vd2mdu 1543 22 ) ) -RRB- cord-014597-66vd2mdu 1543 23 during during IN cord-014597-66vd2mdu 1543 24 the the DT cord-014597-66vd2mdu 1543 25 first first JJ cord-014597-66vd2mdu 1543 26 selection selection NN cord-014597-66vd2mdu 1543 27 phase phase NN cord-014597-66vd2mdu 1543 28 of of IN cord-014597-66vd2mdu 1543 29 three three CD cord-014597-66vd2mdu 1543 30 weeks week NNS cord-014597-66vd2mdu 1543 31 . . . cord-014597-66vd2mdu 1544 1 Afterwards afterwards RB cord-014597-66vd2mdu 1544 2 we -PRON- PRP cord-014597-66vd2mdu 1544 3 omitted omit VBD cord-014597-66vd2mdu 1544 4 the the DT cord-014597-66vd2mdu 1544 5 30 30 CD cord-014597-66vd2mdu 1544 6 nM nm NN cord-014597-66vd2mdu 1544 7 MTX MTX NNP cord-014597-66vd2mdu 1544 8 amplification amplification NN cord-014597-66vd2mdu 1544 9 step step NN cord-014597-66vd2mdu 1544 10 . . . cord-014597-66vd2mdu 1545 1 Thereby thereby RB cord-014597-66vd2mdu 1545 2 , , , cord-014597-66vd2mdu 1545 3 pool pool NN cord-014597-66vd2mdu 1545 4 generation generation NN cord-014597-66vd2mdu 1545 5 finished finish VBD cord-014597-66vd2mdu 1545 6 four four CD cord-014597-66vd2mdu 1545 7 weeks week NNS cord-014597-66vd2mdu 1545 8 earlier early RBR cord-014597-66vd2mdu 1545 9 than than IN cord-014597-66vd2mdu 1545 10 in in IN cord-014597-66vd2mdu 1545 11 the the DT cord-014597-66vd2mdu 1545 12 standard standard JJ cord-014597-66vd2mdu 1545 13 approach approach NN cord-014597-66vd2mdu 1545 14 . . . cord-014597-66vd2mdu 1546 1 To to TO cord-014597-66vd2mdu 1546 2 evaluate evaluate VB cord-014597-66vd2mdu 1546 3 the the DT cord-014597-66vd2mdu 1546 4 stability stability NN cord-014597-66vd2mdu 1546 5 of of IN cord-014597-66vd2mdu 1546 6 cell cell NN cord-014597-66vd2mdu 1546 7 clones clone NNS cord-014597-66vd2mdu 1546 8 derived derive VBN cord-014597-66vd2mdu 1546 9 from from IN cord-014597-66vd2mdu 1546 10 Mini Mini NNP cord-014597-66vd2mdu 1546 11 Pools Pools NNP cord-014597-66vd2mdu 1546 12 ( ( -LRB- cord-014597-66vd2mdu 1546 13 MPs MPs NNP cord-014597-66vd2mdu 1546 14 ) ) -RRB- cord-014597-66vd2mdu 1546 15 generated generate VBD cord-014597-66vd2mdu 1546 16 according accord VBG cord-014597-66vd2mdu 1546 17 to to IN cord-014597-66vd2mdu 1546 18 the the DT cord-014597-66vd2mdu 1546 19 CLD CLD NNP cord-014597-66vd2mdu 1546 20 2.0 2.0 CD cord-014597-66vd2mdu 1546 21 approach approach NN cord-014597-66vd2mdu 1546 22 , , , cord-014597-66vd2mdu 1546 23 stability stability NN cord-014597-66vd2mdu 1546 24 studies study NNS cord-014597-66vd2mdu 1546 25 were be VBD cord-014597-66vd2mdu 1546 26 performed perform VBN cord-014597-66vd2mdu 1546 27 for for IN cord-014597-66vd2mdu 1546 28 eight eight CD cord-014597-66vd2mdu 1546 29 weeks week NNS cord-014597-66vd2mdu 1546 30 , , , cord-014597-66vd2mdu 1546 31 including include VBG cord-014597-66vd2mdu 1546 32 stability stability NN cord-014597-66vd2mdu 1546 33 fed feed VBD cord-014597-66vd2mdu 1546 34 batches batch NNS cord-014597-66vd2mdu 1546 35 at at IN cord-014597-66vd2mdu 1546 36 t=2 t=2 CD cord-014597-66vd2mdu 1546 37 weeks week NNS cord-014597-66vd2mdu 1546 38 and and CC cord-014597-66vd2mdu 1546 39 t=8 t=8 JJ cord-014597-66vd2mdu 1546 40 weeks week NNS cord-014597-66vd2mdu 1546 41 . . . cord-014597-66vd2mdu 1547 1 Altogether altogether RB cord-014597-66vd2mdu 1547 2 three three CD cord-014597-66vd2mdu 1547 3 different different JJ cord-014597-66vd2mdu 1547 4 proteins protein NNS cord-014597-66vd2mdu 1547 5 of of IN cord-014597-66vd2mdu 1547 6 interest interest NN cord-014597-66vd2mdu 1547 7 with with IN cord-014597-66vd2mdu 1547 8 six six CD cord-014597-66vd2mdu 1547 9 cell cell NN cord-014597-66vd2mdu 1547 10 clones clone NNS cord-014597-66vd2mdu 1547 11 each each DT cord-014597-66vd2mdu 1547 12 were be VBD cord-014597-66vd2mdu 1547 13 tested test VBN cord-014597-66vd2mdu 1547 14 . . . cord-014597-66vd2mdu 1548 1 We -PRON- PRP cord-014597-66vd2mdu 1548 2 adapted adapt VBD cord-014597-66vd2mdu 1548 3 our -PRON- PRP$ cord-014597-66vd2mdu 1548 4 cell cell NN cord-014597-66vd2mdu 1548 5 line line NN cord-014597-66vd2mdu 1548 6 development development NN cord-014597-66vd2mdu 1548 7 process process NN cord-014597-66vd2mdu 1548 8 by by IN cord-014597-66vd2mdu 1548 9 increasing increase VBG cord-014597-66vd2mdu 1548 10 the the DT cord-014597-66vd2mdu 1548 11 initial initial JJ cord-014597-66vd2mdu 1548 12 selection selection NN cord-014597-66vd2mdu 1548 13 during during IN cord-014597-66vd2mdu 1548 14 the the DT cord-014597-66vd2mdu 1548 15 first first JJ cord-014597-66vd2mdu 1548 16 selection selection NN cord-014597-66vd2mdu 1548 17 phase phase NN cord-014597-66vd2mdu 1548 18 , , , cord-014597-66vd2mdu 1548 19 thereby thereby RB cord-014597-66vd2mdu 1548 20 allowing allow VBG cord-014597-66vd2mdu 1548 21 the the DT cord-014597-66vd2mdu 1548 22 omission omission NN cord-014597-66vd2mdu 1548 23 of of IN cord-014597-66vd2mdu 1548 24 the the DT cord-014597-66vd2mdu 1548 25 30 30 CD cord-014597-66vd2mdu 1548 26 nM nm NN cord-014597-66vd2mdu 1548 27 MTX MTX NNP cord-014597-66vd2mdu 1548 28 amplification amplification NN cord-014597-66vd2mdu 1548 29 step step NN cord-014597-66vd2mdu 1548 30 . . . cord-014597-66vd2mdu 1549 1 We -PRON- PRP cord-014597-66vd2mdu 1549 2 observed observe VBD cord-014597-66vd2mdu 1549 3 that that IN cord-014597-66vd2mdu 1549 4 the the DT cord-014597-66vd2mdu 1549 5 capacity capacity NN cord-014597-66vd2mdu 1549 6 of of IN cord-014597-66vd2mdu 1549 7 amplifiability amplifiability NN cord-014597-66vd2mdu 1549 8 varied varied JJ cord-014597-66vd2mdu 1549 9 for for IN cord-014597-66vd2mdu 1549 10 different different JJ cord-014597-66vd2mdu 1549 11 products product NNS cord-014597-66vd2mdu 1549 12 . . . cord-014597-66vd2mdu 1550 1 Cell cell NN cord-014597-66vd2mdu 1550 2 lines line NNS cord-014597-66vd2mdu 1550 3 with with IN cord-014597-66vd2mdu 1550 4 a a DT cord-014597-66vd2mdu 1550 5 protein protein NN cord-014597-66vd2mdu 1550 6 titer titer NN cord-014597-66vd2mdu 1550 7 ranging range VBG cord-014597-66vd2mdu 1550 8 from from IN cord-014597-66vd2mdu 1550 9 > > XX cord-014597-66vd2mdu 1550 10 1 1 CD cord-014597-66vd2mdu 1550 11 g g NN cord-014597-66vd2mdu 1550 12 / / SYM cord-014597-66vd2mdu 1550 13 L l NN cord-014597-66vd2mdu 1550 14 to to IN cord-014597-66vd2mdu 1550 15 1.5 1.5 CD cord-014597-66vd2mdu 1550 16 g g NN cord-014597-66vd2mdu 1550 17 / / SYM cord-014597-66vd2mdu 1550 18 L L NNP cord-014597-66vd2mdu 1550 19 ( ( -LRB- cord-014597-66vd2mdu 1550 20 DTE DTE NNP cord-014597-66vd2mdu 1550 21 ) ) -RRB- cord-014597-66vd2mdu 1550 22 in in IN cord-014597-66vd2mdu 1550 23 shake shake NN cord-014597-66vd2mdu 1550 24 flask flask NN cord-014597-66vd2mdu 1550 25 fed feed VBN cord-014597-66vd2mdu 1550 26 - - HYPH cord-014597-66vd2mdu 1550 27 batch batch NN cord-014597-66vd2mdu 1550 28 showed show VBD cord-014597-66vd2mdu 1550 29 to to TO cord-014597-66vd2mdu 1550 30 be be VB cord-014597-66vd2mdu 1550 31 more more RBR cord-014597-66vd2mdu 1550 32 susceptible susceptible JJ cord-014597-66vd2mdu 1550 33 to to IN cord-014597-66vd2mdu 1550 34 increased increase VBN cord-014597-66vd2mdu 1550 35 initial initial JJ cord-014597-66vd2mdu 1550 36 MTX MTX NNP cord-014597-66vd2mdu 1550 37 levels level NNS cord-014597-66vd2mdu 1550 38 and and CC cord-014597-66vd2mdu 1550 39 were be VBD cord-014597-66vd2mdu 1550 40 thus thus RB cord-014597-66vd2mdu 1550 41 not not RB cord-014597-66vd2mdu 1550 42 amplifiable amplifiable JJ cord-014597-66vd2mdu 1550 43 with with IN cord-014597-66vd2mdu 1550 44 30 30 CD cord-014597-66vd2mdu 1550 45 nM nm NN cord-014597-66vd2mdu 1550 46 MTX MTX NNP cord-014597-66vd2mdu 1550 47 . . . cord-014597-66vd2mdu 1551 1 In in IN cord-014597-66vd2mdu 1551 2 contrast contrast NN cord-014597-66vd2mdu 1551 3 , , , cord-014597-66vd2mdu 1551 4 cell cell NN cord-014597-66vd2mdu 1551 5 lines line NNS cord-014597-66vd2mdu 1551 6 with with IN cord-014597-66vd2mdu 1551 7 high high JJ cord-014597-66vd2mdu 1551 8 protein protein NN cord-014597-66vd2mdu 1551 9 titer titer NN cord-014597-66vd2mdu 1551 10 > > XX cord-014597-66vd2mdu 1552 1 1.5 1.5 CD cord-014597-66vd2mdu 1552 2 g g NN cord-014597-66vd2mdu 1552 3 / / SYM cord-014597-66vd2mdu 1552 4 L L NNP cord-014597-66vd2mdu 1552 5 were be VBD cord-014597-66vd2mdu 1552 6 observed observe VBN cord-014597-66vd2mdu 1552 7 to to TO cord-014597-66vd2mdu 1552 8 adapt adapt VB cord-014597-66vd2mdu 1552 9 to to IN cord-014597-66vd2mdu 1552 10 30 30 CD cord-014597-66vd2mdu 1552 11 nM nm NN cord-014597-66vd2mdu 1552 12 MTX MTX NNP cord-014597-66vd2mdu 1552 13 easily easily RB cord-014597-66vd2mdu 1552 14 and and CC cord-014597-66vd2mdu 1552 15 were be VBD cord-014597-66vd2mdu 1552 16 amplifiable amplifiable JJ cord-014597-66vd2mdu 1552 17 . . . cord-014597-66vd2mdu 1553 1 Finale finale NN cord-014597-66vd2mdu 1553 2 shake shake NN cord-014597-66vd2mdu 1553 3 flask flask NN cord-014597-66vd2mdu 1553 4 fed feed VBN cord-014597-66vd2mdu 1553 5 - - HYPH cord-014597-66vd2mdu 1553 6 batch batch NN cord-014597-66vd2mdu 1553 7 data datum NNS cord-014597-66vd2mdu 1553 8 with with IN cord-014597-66vd2mdu 1553 9 CLD CLD NNP cord-014597-66vd2mdu 1553 10 2.0 2.0 CD cord-014597-66vd2mdu 1553 11 clones clone NNS cord-014597-66vd2mdu 1553 12 of of IN cord-014597-66vd2mdu 1553 13 highexpressing highexpresse VBG cord-014597-66vd2mdu 1553 14 products product NNS cord-014597-66vd2mdu 1553 15 showed show VBD cord-014597-66vd2mdu 1553 16 comparable comparable JJ cord-014597-66vd2mdu 1553 17 titers titer NNS cord-014597-66vd2mdu 1553 18 to to IN cord-014597-66vd2mdu 1553 19 clones clone NNS cord-014597-66vd2mdu 1553 20 from from IN cord-014597-66vd2mdu 1553 21 the the DT cord-014597-66vd2mdu 1553 22 standard standard JJ cord-014597-66vd2mdu 1553 23 approach approach NN cord-014597-66vd2mdu 1553 24 . . . cord-014597-66vd2mdu 1554 1 CLD CLD NNP cord-014597-66vd2mdu 1554 2 2.0 2.0 CD cord-014597-66vd2mdu 1554 3 clone clone NN cord-014597-66vd2mdu 1554 4 titers titer NNS cord-014597-66vd2mdu 1554 5 for for IN cord-014597-66vd2mdu 1554 6 DTE DTE NNP cord-014597-66vd2mdu 1554 7 proteins protein NNS cord-014597-66vd2mdu 1554 8 revealed reveal VBN cord-014597-66vd2mdu 1554 9 in in IN cord-014597-66vd2mdu 1554 10 average average JJ cord-014597-66vd2mdu 1554 11 a a DT cord-014597-66vd2mdu 1554 12 2.0-fold 2.0-fold CD cord-014597-66vd2mdu 1554 13 increase increase NN cord-014597-66vd2mdu 1554 14 compared compare VBN cord-014597-66vd2mdu 1554 15 to to IN cord-014597-66vd2mdu 1554 16 clones clone NNS cord-014597-66vd2mdu 1554 17 generated generate VBN cord-014597-66vd2mdu 1554 18 in in IN cord-014597-66vd2mdu 1554 19 the the DT cord-014597-66vd2mdu 1554 20 standard standard JJ cord-014597-66vd2mdu 1554 21 approach approach NN cord-014597-66vd2mdu 1554 22 . . . cord-014597-66vd2mdu 1555 1 Titers titer NNS cord-014597-66vd2mdu 1555 2 of of IN cord-014597-66vd2mdu 1555 3 top top JJ cord-014597-66vd2mdu 1555 4 producing produce VBG cord-014597-66vd2mdu 1555 5 clones clone NNS cord-014597-66vd2mdu 1555 6 were be VBD cord-014597-66vd2mdu 1555 7 in in IN cord-014597-66vd2mdu 1555 8 a a DT cord-014597-66vd2mdu 1555 9 range range NN cord-014597-66vd2mdu 1555 10 of of IN cord-014597-66vd2mdu 1555 11 1.8 1.8 CD cord-014597-66vd2mdu 1555 12 g g NN cord-014597-66vd2mdu 1555 13 / / SYM cord-014597-66vd2mdu 1555 14 L l NN cord-014597-66vd2mdu 1555 15 to to IN cord-014597-66vd2mdu 1555 16 to to IN cord-014597-66vd2mdu 1555 17 2.7 2.7 CD cord-014597-66vd2mdu 1555 18 g g NN cord-014597-66vd2mdu 1555 19 / / SYM cord-014597-66vd2mdu 1555 20 L L NNP cord-014597-66vd2mdu 1555 21 ( ( -LRB- cord-014597-66vd2mdu 1555 22 Fig Fig NNP cord-014597-66vd2mdu 1555 23 . . . cord-014597-66vd2mdu 1555 24 1 1 CD cord-014597-66vd2mdu 1555 25 ) ) -RRB- cord-014597-66vd2mdu 1555 26 . . . cord-014597-66vd2mdu 1556 1 Furthermore furthermore RB cord-014597-66vd2mdu 1556 2 , , , cord-014597-66vd2mdu 1556 3 stability stability NN cord-014597-66vd2mdu 1556 4 data datum NNS cord-014597-66vd2mdu 1556 5 of of IN cord-014597-66vd2mdu 1556 6 CLD2.0 cld2.0 JJ cord-014597-66vd2mdu 1556 7 cell cell NN cord-014597-66vd2mdu 1556 8 clones clone NNS cord-014597-66vd2mdu 1556 9 from from IN cord-014597-66vd2mdu 1556 10 different different JJ cord-014597-66vd2mdu 1556 11 DTE DTE NNP cord-014597-66vd2mdu 1556 12 products product NNS cord-014597-66vd2mdu 1556 13 showed show VBD cord-014597-66vd2mdu 1556 14 a a DT cord-014597-66vd2mdu 1556 15 stable stable JJ cord-014597-66vd2mdu 1556 16 specific specific JJ cord-014597-66vd2mdu 1556 17 productivity productivity NN cord-014597-66vd2mdu 1556 18 in in IN cord-014597-66vd2mdu 1556 19 a a DT cord-014597-66vd2mdu 1556 20 range range NN cord-014597-66vd2mdu 1556 21 of of IN cord-014597-66vd2mdu 1556 22 + + SYM cord-014597-66vd2mdu 1556 23 /-15 /-15 CD cord-014597-66vd2mdu 1556 24 % % NN cord-014597-66vd2mdu 1556 25 over over IN cord-014597-66vd2mdu 1556 26 eight eight CD cord-014597-66vd2mdu 1556 27 weeks week NNS cord-014597-66vd2mdu 1556 28 cultivation cultivation NN cord-014597-66vd2mdu 1556 29 . . . cord-014597-66vd2mdu 1557 1 Fed Fed NNP cord-014597-66vd2mdu 1557 2 - - HYPH cord-014597-66vd2mdu 1557 3 batch batch NN cord-014597-66vd2mdu 1557 4 titer titer NN cord-014597-66vd2mdu 1557 5 from from IN cord-014597-66vd2mdu 1557 6 t=2 t=2 JJ cord-014597-66vd2mdu 1557 7 weeks week NNS cord-014597-66vd2mdu 1557 8 and and CC cord-014597-66vd2mdu 1557 9 t=8 t=8 DT cord-014597-66vd2mdu 1557 10 weeks week NNS cord-014597-66vd2mdu 1557 11 were be VBD cord-014597-66vd2mdu 1557 12 in in IN cord-014597-66vd2mdu 1557 13 a a DT cord-014597-66vd2mdu 1557 14 normal normal JJ cord-014597-66vd2mdu 1557 15 range range NN cord-014597-66vd2mdu 1557 16 of of IN cord-014597-66vd2mdu 1557 17 + + NN cord-014597-66vd2mdu 1557 18 /-20 /-20 CD cord-014597-66vd2mdu 1557 19 % % NN cord-014597-66vd2mdu 1557 20 of of IN cord-014597-66vd2mdu 1557 21 the the DT cord-014597-66vd2mdu 1557 22 standard standard JJ cord-014597-66vd2mdu 1557 23 30 30 CD cord-014597-66vd2mdu 1557 24 nM nm CD cord-014597-66vd2mdu 1557 25 projects project NNS cord-014597-66vd2mdu 1557 26 . . . cord-014597-66vd2mdu 1558 1 Our -PRON- PRP$ cord-014597-66vd2mdu 1558 2 results result NNS cord-014597-66vd2mdu 1558 3 demonstrate demonstrate VBP cord-014597-66vd2mdu 1558 4 that that IN cord-014597-66vd2mdu 1558 5 CLD CLD NNP cord-014597-66vd2mdu 1558 6 2.0 2.0 CD cord-014597-66vd2mdu 1558 7 is be VBZ cord-014597-66vd2mdu 1558 8 a a DT cord-014597-66vd2mdu 1558 9 robust robust JJ cord-014597-66vd2mdu 1558 10 and and CC cord-014597-66vd2mdu 1558 11 reliable reliable JJ cord-014597-66vd2mdu 1558 12 process process NN cord-014597-66vd2mdu 1558 13 for for IN cord-014597-66vd2mdu 1558 14 standard standard JJ cord-014597-66vd2mdu 1558 15 products product NNS cord-014597-66vd2mdu 1558 16 ( ( -LRB- cord-014597-66vd2mdu 1558 17 mAb mab NN cord-014597-66vd2mdu 1558 18 ) ) -RRB- cord-014597-66vd2mdu 1558 19 and and CC cord-014597-66vd2mdu 1558 20 DTE DTE NNP cord-014597-66vd2mdu 1558 21 proteins protein NNS cord-014597-66vd2mdu 1558 22 . . . cord-014597-66vd2mdu 1559 1 With with IN cord-014597-66vd2mdu 1559 2 our -PRON- PRP$ cord-014597-66vd2mdu 1559 3 new new JJ cord-014597-66vd2mdu 1559 4 process process NN cord-014597-66vd2mdu 1559 5 , , , cord-014597-66vd2mdu 1559 6 we -PRON- PRP cord-014597-66vd2mdu 1559 7 were be VBD cord-014597-66vd2mdu 1559 8 able able JJ cord-014597-66vd2mdu 1559 9 to to TO cord-014597-66vd2mdu 1559 10 increase increase VB cord-014597-66vd2mdu 1559 11 titer titer NN cord-014597-66vd2mdu 1559 12 of of IN cord-014597-66vd2mdu 1559 13 difficult difficult JJ cord-014597-66vd2mdu 1559 14 - - HYPH cord-014597-66vd2mdu 1559 15 to to TO cord-014597-66vd2mdu 1559 16 - - HYPH cord-014597-66vd2mdu 1559 17 express express VB cord-014597-66vd2mdu 1559 18 proteins protein NNS cord-014597-66vd2mdu 1559 19 up up IN cord-014597-66vd2mdu 1559 20 to to IN cord-014597-66vd2mdu 1559 21 200 200 CD cord-014597-66vd2mdu 1559 22 % % NN cord-014597-66vd2mdu 1559 23 . . . cord-014597-66vd2mdu 1560 1 By by IN cord-014597-66vd2mdu 1560 2 omitting omit VBG cord-014597-66vd2mdu 1560 3 the the DT cord-014597-66vd2mdu 1560 4 amplification amplification NN cord-014597-66vd2mdu 1560 5 step step NN cord-014597-66vd2mdu 1560 6 ( ( -LRB- cord-014597-66vd2mdu 1560 7 30 30 CD cord-014597-66vd2mdu 1560 8 nM nm NN cord-014597-66vd2mdu 1560 9 MTX MTX NNP cord-014597-66vd2mdu 1560 10 ) ) -RRB- cord-014597-66vd2mdu 1560 11 96 96 CD cord-014597-66vd2mdu 1560 12 % % NN cord-014597-66vd2mdu 1560 13 of of IN cord-014597-66vd2mdu 1560 14 generated generate VBN cord-014597-66vd2mdu 1560 15 clones clone NNS cord-014597-66vd2mdu 1560 16 were be VBD cord-014597-66vd2mdu 1560 17 stable stable JJ cord-014597-66vd2mdu 1560 18 over over IN cord-014597-66vd2mdu 1560 19 eight eight CD cord-014597-66vd2mdu 1560 20 weeks week NNS cord-014597-66vd2mdu 1560 21 cultivation cultivation NN cord-014597-66vd2mdu 1560 22 time time NN cord-014597-66vd2mdu 1560 23 . . . cord-014597-66vd2mdu 1561 1 Additionally additionally RB cord-014597-66vd2mdu 1561 2 using use VBG cord-014597-66vd2mdu 1561 3 the the DT cord-014597-66vd2mdu 1561 4 CLD2.0 cld2.0 JJ cord-014597-66vd2mdu 1561 5 approach approach NN cord-014597-66vd2mdu 1561 6 , , , cord-014597-66vd2mdu 1561 7 the the DT cord-014597-66vd2mdu 1561 8 time time NN cord-014597-66vd2mdu 1561 9 line line NN cord-014597-66vd2mdu 1561 10 from from IN cord-014597-66vd2mdu 1561 11 DNA DNA NNP cord-014597-66vd2mdu 1561 12 to to IN cord-014597-66vd2mdu 1561 13 RCB RCB NNP cord-014597-66vd2mdu 1561 14 was be VBD cord-014597-66vd2mdu 1561 15 reduced reduce VBN cord-014597-66vd2mdu 1561 16 to to IN cord-014597-66vd2mdu 1561 17 5 5 CD cord-014597-66vd2mdu 1561 18 months month NNS cord-014597-66vd2mdu 1561 19 . . . cord-014597-66vd2mdu 1562 1 Background Background NNP cord-014597-66vd2mdu 1562 2 CHO CHO NNP cord-014597-66vd2mdu 1562 3 cells cell NNS cord-014597-66vd2mdu 1562 4 have have VBP cord-014597-66vd2mdu 1562 5 become become VBN cord-014597-66vd2mdu 1562 6 the the DT cord-014597-66vd2mdu 1562 7 most most RBS cord-014597-66vd2mdu 1562 8 popular popular JJ cord-014597-66vd2mdu 1562 9 platform platform NN cord-014597-66vd2mdu 1562 10 for for IN cord-014597-66vd2mdu 1562 11 production production NN cord-014597-66vd2mdu 1562 12 of of IN cord-014597-66vd2mdu 1562 13 therapeutic therapeutic JJ cord-014597-66vd2mdu 1562 14 proteins protein NNS cord-014597-66vd2mdu 1562 15 [ [ -LRB- cord-014597-66vd2mdu 1562 16 1 1 CD cord-014597-66vd2mdu 1562 17 ] ] -RRB- cord-014597-66vd2mdu 1562 18 . . . cord-014597-66vd2mdu 1563 1 However however RB cord-014597-66vd2mdu 1563 2 , , , cord-014597-66vd2mdu 1563 3 the the DT cord-014597-66vd2mdu 1563 4 generation generation NN cord-014597-66vd2mdu 1563 5 of of IN cord-014597-66vd2mdu 1563 6 high high JJ cord-014597-66vd2mdu 1563 7 - - HYPH cord-014597-66vd2mdu 1563 8 producer producer NN cord-014597-66vd2mdu 1563 9 cells cell NNS cord-014597-66vd2mdu 1563 10 is be VBZ cord-014597-66vd2mdu 1563 11 a a DT cord-014597-66vd2mdu 1563 12 time time NN cord-014597-66vd2mdu 1563 13 - - HYPH cord-014597-66vd2mdu 1563 14 consuming consume VBG cord-014597-66vd2mdu 1563 15 and and CC cord-014597-66vd2mdu 1563 16 labor labor NN cord-014597-66vd2mdu 1563 17 - - HYPH cord-014597-66vd2mdu 1563 18 intensive intensive JJ cord-014597-66vd2mdu 1563 19 process process NN cord-014597-66vd2mdu 1563 20 that that WDT cord-014597-66vd2mdu 1563 21 requires require VBZ cord-014597-66vd2mdu 1563 22 the the DT cord-014597-66vd2mdu 1563 23 screening screening NN cord-014597-66vd2mdu 1563 24 of of IN cord-014597-66vd2mdu 1563 25 large large JJ cord-014597-66vd2mdu 1563 26 amount amount NN cord-014597-66vd2mdu 1563 27 of of IN cord-014597-66vd2mdu 1563 28 cells cell NNS cord-014597-66vd2mdu 1563 29 to to TO cord-014597-66vd2mdu 1563 30 get get VB cord-014597-66vd2mdu 1563 31 a a DT cord-014597-66vd2mdu 1563 32 clone clone NN cord-014597-66vd2mdu 1563 33 of of IN cord-014597-66vd2mdu 1563 34 high high JJ cord-014597-66vd2mdu 1563 35 titer titer NN cord-014597-66vd2mdu 1563 36 and and CC cord-014597-66vd2mdu 1563 37 stability stability NN cord-014597-66vd2mdu 1563 38 . . . cord-014597-66vd2mdu 1564 1 Since since IN cord-014597-66vd2mdu 1564 2 the the DT cord-014597-66vd2mdu 1564 3 expression expression NN cord-014597-66vd2mdu 1564 4 titer titer NN cord-014597-66vd2mdu 1564 5 and and CC cord-014597-66vd2mdu 1564 6 stability stability NN cord-014597-66vd2mdu 1564 7 of of IN cord-014597-66vd2mdu 1564 8 clone clone NN cord-014597-66vd2mdu 1564 9 is be VBZ cord-014597-66vd2mdu 1564 10 highly highly RB cord-014597-66vd2mdu 1564 11 dependent dependent JJ cord-014597-66vd2mdu 1564 12 on on IN cord-014597-66vd2mdu 1564 13 the the DT cord-014597-66vd2mdu 1564 14 site site NN cord-014597-66vd2mdu 1564 15 of of IN cord-014597-66vd2mdu 1564 16 integration integration NN cord-014597-66vd2mdu 1564 17 , , , cord-014597-66vd2mdu 1564 18 we -PRON- PRP cord-014597-66vd2mdu 1564 19 demonstrated demonstrate VBD cord-014597-66vd2mdu 1564 20 a a DT cord-014597-66vd2mdu 1564 21 new new JJ cord-014597-66vd2mdu 1564 22 cell cell NN cord-014597-66vd2mdu 1564 23 line line NN cord-014597-66vd2mdu 1564 24 development development NN cord-014597-66vd2mdu 1564 25 strategy strategy NN cord-014597-66vd2mdu 1564 26 by by IN cord-014597-66vd2mdu 1564 27 using use VBG cord-014597-66vd2mdu 1564 28 NGS NGS NNP cord-014597-66vd2mdu 1564 29 to to TO cord-014597-66vd2mdu 1564 30 identify identify VB cord-014597-66vd2mdu 1564 31 the the DT cord-014597-66vd2mdu 1564 32 integration integration NN cord-014597-66vd2mdu 1564 33 site site NN cord-014597-66vd2mdu 1564 34 and and CC cord-014597-66vd2mdu 1564 35 using use VBG cord-014597-66vd2mdu 1564 36 CRISPR CRISPR NNP cord-014597-66vd2mdu 1564 37 / / SYM cord-014597-66vd2mdu 1564 38 Cas9 Cas9 NNP cord-014597-66vd2mdu 1564 39 to to TO cord-014597-66vd2mdu 1564 40 generate generate VB cord-014597-66vd2mdu 1564 41 the the DT cord-014597-66vd2mdu 1564 42 target target NN cord-014597-66vd2mdu 1564 43 integrated integrate VBN cord-014597-66vd2mdu 1564 44 high high JJ cord-014597-66vd2mdu 1564 45 producing produce VBG cord-014597-66vd2mdu 1564 46 cell cell NN cord-014597-66vd2mdu 1564 47 lines line NNS cord-014597-66vd2mdu 1564 48 [ [ -LRB- cord-014597-66vd2mdu 1564 49 1 1 CD cord-014597-66vd2mdu 1564 50 , , , cord-014597-66vd2mdu 1564 51 2 2 CD cord-014597-66vd2mdu 1564 52 ] ] -RRB- cord-014597-66vd2mdu 1564 53 . . . cord-014597-66vd2mdu 1565 1 To to TO cord-014597-66vd2mdu 1565 2 identify identify VB cord-014597-66vd2mdu 1565 3 the the DT cord-014597-66vd2mdu 1565 4 high high JJ cord-014597-66vd2mdu 1565 5 expression expression NN cord-014597-66vd2mdu 1565 6 sites site NNS cord-014597-66vd2mdu 1565 7 in in IN cord-014597-66vd2mdu 1565 8 the the DT cord-014597-66vd2mdu 1565 9 CHO CHO NNP cord-014597-66vd2mdu 1565 10 cells cell NNS cord-014597-66vd2mdu 1565 11 , , , cord-014597-66vd2mdu 1565 12 we -PRON- PRP cord-014597-66vd2mdu 1565 13 employed employ VBD cord-014597-66vd2mdu 1565 14 NGS NGS NNP cord-014597-66vd2mdu 1565 15 to to TO cord-014597-66vd2mdu 1565 16 analyze analyze VB cord-014597-66vd2mdu 1565 17 the the DT cord-014597-66vd2mdu 1565 18 integration integration NN cord-014597-66vd2mdu 1565 19 sites site NNS cord-014597-66vd2mdu 1565 20 of of IN cord-014597-66vd2mdu 1565 21 a a DT cord-014597-66vd2mdu 1565 22 high high JJ cord-014597-66vd2mdu 1565 23 producing produce VBG cord-014597-66vd2mdu 1565 24 cell cell NN cord-014597-66vd2mdu 1565 25 line line NN cord-014597-66vd2mdu 1565 26 ( ( -LRB- cord-014597-66vd2mdu 1565 27 titer titer NN cord-014597-66vd2mdu 1565 28 > > XX cord-014597-66vd2mdu 1565 29 3g 3g NNP cord-014597-66vd2mdu 1565 30 / / SYM cord-014597-66vd2mdu 1565 31 L L NNP cord-014597-66vd2mdu 1565 32 ) ) -RRB- cord-014597-66vd2mdu 1565 33 . . . cord-014597-66vd2mdu 1566 1 The the DT cord-014597-66vd2mdu 1566 2 pair pair NN cord-014597-66vd2mdu 1566 3 - - HYPH cord-014597-66vd2mdu 1566 4 end end NN cord-014597-66vd2mdu 1566 5 reads read VBZ cord-014597-66vd2mdu 1566 6 with with IN cord-014597-66vd2mdu 1566 7 one one CD cord-014597-66vd2mdu 1566 8 read read NN cord-014597-66vd2mdu 1566 9 mapped map VBN cord-014597-66vd2mdu 1566 10 to to IN cord-014597-66vd2mdu 1566 11 the the DT cord-014597-66vd2mdu 1566 12 vector vector NN cord-014597-66vd2mdu 1566 13 and and CC cord-014597-66vd2mdu 1566 14 the the DT cord-014597-66vd2mdu 1566 15 other other JJ cord-014597-66vd2mdu 1566 16 read read NN cord-014597-66vd2mdu 1566 17 mapped map VBN cord-014597-66vd2mdu 1566 18 to to IN cord-014597-66vd2mdu 1566 19 the the DT cord-014597-66vd2mdu 1566 20 CHO CHO NNP cord-014597-66vd2mdu 1566 21 reference reference NN cord-014597-66vd2mdu 1566 22 genome genome NN cord-014597-66vd2mdu 1566 23 are be VBP cord-014597-66vd2mdu 1566 24 extracted extract VBN cord-014597-66vd2mdu 1566 25 to to TO cord-014597-66vd2mdu 1566 26 identify identify VB cord-014597-66vd2mdu 1566 27 the the DT cord-014597-66vd2mdu 1566 28 integration integration NN cord-014597-66vd2mdu 1566 29 sites site NNS cord-014597-66vd2mdu 1566 30 . . . cord-014597-66vd2mdu 1567 1 To to TO cord-014597-66vd2mdu 1567 2 test test VB cord-014597-66vd2mdu 1567 3 the the DT cord-014597-66vd2mdu 1567 4 expression expression NN cord-014597-66vd2mdu 1567 5 activity activity NN cord-014597-66vd2mdu 1567 6 of of IN cord-014597-66vd2mdu 1567 7 the the DT cord-014597-66vd2mdu 1567 8 integration integration NN cord-014597-66vd2mdu 1567 9 sites site NNS cord-014597-66vd2mdu 1567 10 , , , cord-014597-66vd2mdu 1567 11 we -PRON- PRP cord-014597-66vd2mdu 1567 12 employed employ VBD cord-014597-66vd2mdu 1567 13 CRISPR CRISPR NNP cord-014597-66vd2mdu 1567 14 / / SYM cord-014597-66vd2mdu 1567 15 Cas9 Cas9 NNP cord-014597-66vd2mdu 1567 16 to to TO cord-014597-66vd2mdu 1567 17 specifically specifically RB cord-014597-66vd2mdu 1567 18 integrate integrate VB cord-014597-66vd2mdu 1567 19 the the DT cord-014597-66vd2mdu 1567 20 antibody antibody NN cord-014597-66vd2mdu 1567 21 gene gene NN cord-014597-66vd2mdu 1567 22 into into IN cord-014597-66vd2mdu 1567 23 CHO CHO NNP cord-014597-66vd2mdu 1567 24 genome genome NN cord-014597-66vd2mdu 1567 25 for for IN cord-014597-66vd2mdu 1567 26 expression expression NN cord-014597-66vd2mdu 1567 27 . . . cord-014597-66vd2mdu 1568 1 Our -PRON- PRP$ cord-014597-66vd2mdu 1568 2 data datum NNS cord-014597-66vd2mdu 1568 3 showed show VBD cord-014597-66vd2mdu 1568 4 4 4 CD cord-014597-66vd2mdu 1568 5 integration integration NN cord-014597-66vd2mdu 1568 6 sites site NNS cord-014597-66vd2mdu 1568 7 are be VBP cord-014597-66vd2mdu 1568 8 in in IN cord-014597-66vd2mdu 1568 9 the the DT cord-014597-66vd2mdu 1568 10 high high JJ cord-014597-66vd2mdu 1568 11 producing produce VBG cord-014597-66vd2mdu 1568 12 cell cell NN cord-014597-66vd2mdu 1568 13 line line NN cord-014597-66vd2mdu 1568 14 . . . cord-014597-66vd2mdu 1569 1 Among among IN cord-014597-66vd2mdu 1569 2 the the DT cord-014597-66vd2mdu 1569 3 4 4 CD cord-014597-66vd2mdu 1569 4 integration integration NN cord-014597-66vd2mdu 1569 5 site site NN cord-014597-66vd2mdu 1569 6 , , , cord-014597-66vd2mdu 1569 7 IS1 is1 NN cord-014597-66vd2mdu 1569 8 integration integration NN cord-014597-66vd2mdu 1569 9 site site NN cord-014597-66vd2mdu 1569 10 was be VBD cord-014597-66vd2mdu 1569 11 tested test VBN cord-014597-66vd2mdu 1569 12 by by IN cord-014597-66vd2mdu 1569 13 CRISPR/ CRISPR/ NNP cord-014597-66vd2mdu 1569 14 Cas9 Cas9 NNP cord-014597-66vd2mdu 1569 15 for for IN cord-014597-66vd2mdu 1569 16 target target NN cord-014597-66vd2mdu 1569 17 integration integration NN cord-014597-66vd2mdu 1569 18 of of IN cord-014597-66vd2mdu 1569 19 antibody antibody NN cord-014597-66vd2mdu 1569 20 gene gene NN cord-014597-66vd2mdu 1569 21 for for IN cord-014597-66vd2mdu 1569 22 expression expression NN cord-014597-66vd2mdu 1569 23 . . . cord-014597-66vd2mdu 1570 1 The the DT cord-014597-66vd2mdu 1570 2 IS1target IS1target NNP cord-014597-66vd2mdu 1570 3 integrated integrate VBD cord-014597-66vd2mdu 1570 4 cell cell NN cord-014597-66vd2mdu 1570 5 pool pool NN cord-014597-66vd2mdu 1570 6 present present VBP cord-014597-66vd2mdu 1570 7 higher high JJR cord-014597-66vd2mdu 1570 8 expression expression NN cord-014597-66vd2mdu 1570 9 titer titer NN cord-014597-66vd2mdu 1570 10 than than IN cord-014597-66vd2mdu 1570 11 cell cell NN cord-014597-66vd2mdu 1570 12 pool pool NN cord-014597-66vd2mdu 1570 13 generated generate VBN cord-014597-66vd2mdu 1570 14 by by IN cord-014597-66vd2mdu 1570 15 target target NN cord-014597-66vd2mdu 1570 16 integration integration NN cord-014597-66vd2mdu 1570 17 into into IN cord-014597-66vd2mdu 1570 18 other other JJ cord-014597-66vd2mdu 1570 19 integration integration NN cord-014597-66vd2mdu 1570 20 sites site NNS cord-014597-66vd2mdu 1570 21 ( ( -LRB- cord-014597-66vd2mdu 1570 22 Fig Fig NNP cord-014597-66vd2mdu 1570 23 . . . cord-014597-66vd2mdu 1570 24 1a 1a CD cord-014597-66vd2mdu 1570 25 ) ) -RRB- cord-014597-66vd2mdu 1570 26 . . . cord-014597-66vd2mdu 1571 1 The the DT cord-014597-66vd2mdu 1571 2 single single JJ cord-014597-66vd2mdu 1571 3 cell cell NN cord-014597-66vd2mdu 1571 4 clones clone NNS cord-014597-66vd2mdu 1571 5 derived derive VBN cord-014597-66vd2mdu 1571 6 from from IN cord-014597-66vd2mdu 1571 7 IS1-target is1-target DT cord-014597-66vd2mdu 1571 8 integrated integrated JJ cord-014597-66vd2mdu 1571 9 cell cell NN cord-014597-66vd2mdu 1571 10 pool pool NN cord-014597-66vd2mdu 1571 11 had have VBD cord-014597-66vd2mdu 1571 12 low low JJ cord-014597-66vd2mdu 1571 13 copy copy NN cord-014597-66vd2mdu 1571 14 number number NN cord-014597-66vd2mdu 1571 15 of of IN cord-014597-66vd2mdu 1571 16 GOI GOI NNP cord-014597-66vd2mdu 1571 17 ( ( -LRB- cord-014597-66vd2mdu 1571 18 Fig fig NN cord-014597-66vd2mdu 1571 19 . . . cord-014597-66vd2mdu 1571 20 1b 1b CD cord-014597-66vd2mdu 1571 21 ) ) -RRB- cord-014597-66vd2mdu 1571 22 . . . cord-014597-66vd2mdu 1572 1 After after IN cord-014597-66vd2mdu 1572 2 normalization normalization NN cord-014597-66vd2mdu 1572 3 with with IN cord-014597-66vd2mdu 1572 4 copy copy JJ cord-014597-66vd2mdu 1572 5 numbers number NNS cord-014597-66vd2mdu 1572 6 , , , cord-014597-66vd2mdu 1572 7 the the DT cord-014597-66vd2mdu 1572 8 single single JJ cord-014597-66vd2mdu 1572 9 cell cell NN cord-014597-66vd2mdu 1572 10 clones clone NNS cord-014597-66vd2mdu 1572 11 derived derive VBN cord-014597-66vd2mdu 1572 12 from from IN cord-014597-66vd2mdu 1572 13 IS1-target is1-target DT cord-014597-66vd2mdu 1572 14 integrated integrated JJ cord-014597-66vd2mdu 1572 15 cell cell NN cord-014597-66vd2mdu 1572 16 pool pool NN cord-014597-66vd2mdu 1572 17 showed show VBD cord-014597-66vd2mdu 1572 18 high high JJ cord-014597-66vd2mdu 1572 19 titer titer NN cord-014597-66vd2mdu 1572 20 per per IN cord-014597-66vd2mdu 1572 21 copy copy NN cord-014597-66vd2mdu 1572 22 ( ( -LRB- cord-014597-66vd2mdu 1572 23 123~583 123~583 CD cord-014597-66vd2mdu 1572 24 mg mg NNP cord-014597-66vd2mdu 1572 25 / / SYM cord-014597-66vd2mdu 1572 26 L L NNP cord-014597-66vd2mdu 1572 27 / / SYM cord-014597-66vd2mdu 1572 28 copy copy NN cord-014597-66vd2mdu 1572 29 ) ) -RRB- cord-014597-66vd2mdu 1573 1 ( ( -LRB- cord-014597-66vd2mdu 1573 2 Fig Fig NNP cord-014597-66vd2mdu 1573 3 . . . cord-014597-66vd2mdu 1573 4 1c 1c CD cord-014597-66vd2mdu 1573 5 ) ) -RRB- cord-014597-66vd2mdu 1573 6 . . . cord-014597-66vd2mdu 1574 1 This this DT cord-014597-66vd2mdu 1574 2 study study NN cord-014597-66vd2mdu 1574 3 demonstrated demonstrate VBD cord-014597-66vd2mdu 1574 4 the the DT cord-014597-66vd2mdu 1574 5 generation generation NN cord-014597-66vd2mdu 1574 6 of of IN cord-014597-66vd2mdu 1574 7 high high RB cord-014597-66vd2mdu 1574 8 - - HYPH cord-014597-66vd2mdu 1574 9 producing produce VBG cord-014597-66vd2mdu 1574 10 cell cell NN cord-014597-66vd2mdu 1574 11 lines line NNS cord-014597-66vd2mdu 1574 12 by by IN cord-014597-66vd2mdu 1574 13 CRISPR CRISPR NNP cord-014597-66vd2mdu 1574 14 / / SYM cord-014597-66vd2mdu 1574 15 Cas9 Cas9 NNP cord-014597-66vd2mdu 1574 16 mediated mediate VBN cord-014597-66vd2mdu 1574 17 target target NN cord-014597-66vd2mdu 1574 18 integration integration NN cord-014597-66vd2mdu 1574 19 . . . cord-014597-66vd2mdu 1575 1 This this DT cord-014597-66vd2mdu 1575 2 approach approach NN cord-014597-66vd2mdu 1575 3 will will MD cord-014597-66vd2mdu 1575 4 cost cost VB cord-014597-66vd2mdu 1575 5 less less JJR cord-014597-66vd2mdu 1575 6 time time NN cord-014597-66vd2mdu 1575 7 and and CC cord-014597-66vd2mdu 1575 8 labor labor NN cord-014597-66vd2mdu 1575 9 than than IN cord-014597-66vd2mdu 1575 10 traditional traditional JJ cord-014597-66vd2mdu 1575 11 method method NN cord-014597-66vd2mdu 1575 12 . . . cord-014597-66vd2mdu 1576 1 The the DT cord-014597-66vd2mdu 1576 2 active active JJ cord-014597-66vd2mdu 1576 3 integration integration NN cord-014597-66vd2mdu 1576 4 site site NN cord-014597-66vd2mdu 1576 5 will will MD cord-014597-66vd2mdu 1576 6 serve serve VB cord-014597-66vd2mdu 1576 7 as as IN cord-014597-66vd2mdu 1576 8 a a DT cord-014597-66vd2mdu 1576 9 platform platform NN cord-014597-66vd2mdu 1576 10 like like IN cord-014597-66vd2mdu 1576 11 a a DT cord-014597-66vd2mdu 1576 12 cassette cassette NN cord-014597-66vd2mdu 1576 13 player player NN cord-014597-66vd2mdu 1576 14 for for IN cord-014597-66vd2mdu 1576 15 therapeutic therapeutic JJ cord-014597-66vd2mdu 1576 16 antibody antibody NN cord-014597-66vd2mdu 1576 17 production production NN cord-014597-66vd2mdu 1576 18 . . . cord-014597-66vd2mdu 1577 1 Background Background NNP cord-014597-66vd2mdu 1577 2 CHO CHO NNP cord-014597-66vd2mdu 1577 3 , , , cord-014597-66vd2mdu 1577 4 HEK HEK NNP cord-014597-66vd2mdu 1577 5 and and CC cord-014597-66vd2mdu 1577 6 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1577 7 are be VBP cord-014597-66vd2mdu 1577 8 the the DT cord-014597-66vd2mdu 1577 9 dominant dominant JJ cord-014597-66vd2mdu 1577 10 host host NN cord-014597-66vd2mdu 1577 11 cells cell NNS cord-014597-66vd2mdu 1577 12 for for IN cord-014597-66vd2mdu 1577 13 biologics biologic NNS cord-014597-66vd2mdu 1577 14 drug drug NN cord-014597-66vd2mdu 1577 15 production production NN cord-014597-66vd2mdu 1577 16 . . . cord-014597-66vd2mdu 1578 1 Achieving achieve VBG cord-014597-66vd2mdu 1578 2 high high JJ cord-014597-66vd2mdu 1578 3 level level NN cord-014597-66vd2mdu 1578 4 of of IN cord-014597-66vd2mdu 1578 5 recombinant recombinant JJ cord-014597-66vd2mdu 1578 6 protein protein NN cord-014597-66vd2mdu 1578 7 production production NN cord-014597-66vd2mdu 1578 8 by by IN cord-014597-66vd2mdu 1578 9 these these DT cord-014597-66vd2mdu 1578 10 cell cell NN cord-014597-66vd2mdu 1578 11 lines line NNS cord-014597-66vd2mdu 1578 12 still still RB cord-014597-66vd2mdu 1578 13 remains remain VBZ cord-014597-66vd2mdu 1578 14 a a DT cord-014597-66vd2mdu 1578 15 challenge challenge NN cord-014597-66vd2mdu 1578 16 . . . cord-014597-66vd2mdu 1579 1 In in IN cord-014597-66vd2mdu 1579 2 order order NN cord-014597-66vd2mdu 1579 3 to to TO cord-014597-66vd2mdu 1579 4 understand understand VB cord-014597-66vd2mdu 1579 5 the the DT cord-014597-66vd2mdu 1579 6 potential potential JJ cord-014597-66vd2mdu 1579 7 roles role NNS cord-014597-66vd2mdu 1579 8 of of IN cord-014597-66vd2mdu 1579 9 lipids lipid NNS cord-014597-66vd2mdu 1579 10 in in IN cord-014597-66vd2mdu 1579 11 protein protein NN cord-014597-66vd2mdu 1579 12 production production NN cord-014597-66vd2mdu 1579 13 , , , cord-014597-66vd2mdu 1579 14 secretion secretion NN cord-014597-66vd2mdu 1579 15 , , , cord-014597-66vd2mdu 1579 16 vesicular vesicular JJ cord-014597-66vd2mdu 1579 17 transport transport NN cord-014597-66vd2mdu 1579 18 and and CC cord-014597-66vd2mdu 1579 19 energy energy NN cord-014597-66vd2mdu 1579 20 metabolism metabolism NN cord-014597-66vd2mdu 1579 21 , , , cord-014597-66vd2mdu 1579 22 we -PRON- PRP cord-014597-66vd2mdu 1579 23 coupled couple VBD cord-014597-66vd2mdu 1579 24 high high JJ cord-014597-66vd2mdu 1579 25 - - HYPH cord-014597-66vd2mdu 1579 26 throughput throughput NN cord-014597-66vd2mdu 1579 27 transcriptomics transcriptomic NNS cord-014597-66vd2mdu 1579 28 and and CC cord-014597-66vd2mdu 1579 29 lipidomics lipidomics NNP cord-014597-66vd2mdu 1579 30 technologies technology NNS cord-014597-66vd2mdu 1579 31 . . . cord-014597-66vd2mdu 1580 1 Quantitative quantitative JJ cord-014597-66vd2mdu 1580 2 lipidomics lipidomic NNS cord-014597-66vd2mdu 1580 3 is be VBZ cord-014597-66vd2mdu 1580 4 an an DT cord-014597-66vd2mdu 1580 5 emerging emerge VBG cord-014597-66vd2mdu 1580 6 ' ' `` cord-014597-66vd2mdu 1580 7 omics omic NNS cord-014597-66vd2mdu 1580 8 technology technology NN cord-014597-66vd2mdu 1580 9 which which WDT cord-014597-66vd2mdu 1580 10 can can MD cord-014597-66vd2mdu 1580 11 help help VB cord-014597-66vd2mdu 1580 12 us -PRON- PRP cord-014597-66vd2mdu 1580 13 understand understand VB cord-014597-66vd2mdu 1580 14 the the DT cord-014597-66vd2mdu 1580 15 physiological physiological JJ cord-014597-66vd2mdu 1580 16 limitations limitation NNS cord-014597-66vd2mdu 1580 17 of of IN cord-014597-66vd2mdu 1580 18 each each DT cord-014597-66vd2mdu 1580 19 cell cell NN cord-014597-66vd2mdu 1580 20 line line NN cord-014597-66vd2mdu 1580 21 . . . cord-014597-66vd2mdu 1581 1 The the DT cord-014597-66vd2mdu 1581 2 two two CD cord-014597-66vd2mdu 1581 3 types type NNS cord-014597-66vd2mdu 1581 4 of of IN cord-014597-66vd2mdu 1581 5 major major JJ cord-014597-66vd2mdu 1581 6 lipid lipid NN cord-014597-66vd2mdu 1581 7 groups group NNS cord-014597-66vd2mdu 1581 8 in in IN cord-014597-66vd2mdu 1581 9 cells cell NNS cord-014597-66vd2mdu 1581 10 are be VBP cord-014597-66vd2mdu 1581 11 non non JJ cord-014597-66vd2mdu 1581 12 - - JJ cord-014597-66vd2mdu 1581 13 polar polar JJ cord-014597-66vd2mdu 1581 14 and and CC cord-014597-66vd2mdu 1581 15 polar polar JJ cord-014597-66vd2mdu 1581 16 lipids lipid NNS cord-014597-66vd2mdu 1581 17 . . . cord-014597-66vd2mdu 1582 1 Polar polar JJ cord-014597-66vd2mdu 1582 2 lipids lipid NNS cord-014597-66vd2mdu 1582 3 such such JJ cord-014597-66vd2mdu 1582 4 as as IN cord-014597-66vd2mdu 1582 5 glycerophospholipids glycerophospholipid NNS cord-014597-66vd2mdu 1582 6 ( ( -LRB- cord-014597-66vd2mdu 1582 7 PLs pl NNS cord-014597-66vd2mdu 1582 8 ) ) -RRB- cord-014597-66vd2mdu 1582 9 include include VBP cord-014597-66vd2mdu 1582 10 phosphatidylethanolamine phosphatidylethanolamine JJ cord-014597-66vd2mdu 1582 11 ( ( -LRB- cord-014597-66vd2mdu 1582 12 PE PE NNP cord-014597-66vd2mdu 1582 13 ) ) -RRB- cord-014597-66vd2mdu 1582 14 , , , cord-014597-66vd2mdu 1582 15 phosphatidylcholine phosphatidylcholine NN cord-014597-66vd2mdu 1582 16 ( ( -LRB- cord-014597-66vd2mdu 1582 17 PC pc NN cord-014597-66vd2mdu 1582 18 ) ) -RRB- cord-014597-66vd2mdu 1582 19 , , , cord-014597-66vd2mdu 1582 20 phosphatidylinositol phosphatidylinositol JJ cord-014597-66vd2mdu 1582 21 ( ( -LRB- cord-014597-66vd2mdu 1582 22 PI PI NNP cord-014597-66vd2mdu 1582 23 ) ) -RRB- cord-014597-66vd2mdu 1582 24 , , , cord-014597-66vd2mdu 1582 25 phosphatidylserine phosphatidylserine NN cord-014597-66vd2mdu 1582 26 ( ( -LRB- cord-014597-66vd2mdu 1582 27 PS PS NNP cord-014597-66vd2mdu 1582 28 ) ) -RRB- cord-014597-66vd2mdu 1582 29 , , , cord-014597-66vd2mdu 1582 30 phosphatidylglycerol phosphatidylglycerol NNP cord-014597-66vd2mdu 1582 31 ( ( -LRB- cord-014597-66vd2mdu 1582 32 PG PG NNP cord-014597-66vd2mdu 1582 33 ) ) -RRB- cord-014597-66vd2mdu 1582 34 , , , cord-014597-66vd2mdu 1582 35 and and CC cord-014597-66vd2mdu 1582 36 phosphatidic phosphatidic JJ cord-014597-66vd2mdu 1582 37 acid acid NN cord-014597-66vd2mdu 1582 38 ( ( -LRB- cord-014597-66vd2mdu 1582 39 PA PA NNP cord-014597-66vd2mdu 1582 40 ) ) -RRB- cord-014597-66vd2mdu 1582 41 . . . cord-014597-66vd2mdu 1583 1 In in IN cord-014597-66vd2mdu 1583 2 this this DT cord-014597-66vd2mdu 1583 3 study study NN cord-014597-66vd2mdu 1583 4 ; ; : cord-014597-66vd2mdu 1583 5 we -PRON- PRP cord-014597-66vd2mdu 1583 6 integrated integrate VBD cord-014597-66vd2mdu 1583 7 two two CD cord-014597-66vd2mdu 1583 8 dimensional dimensional JJ cord-014597-66vd2mdu 1583 9 high high JJ cord-014597-66vd2mdu 1583 10 performance performance NN cord-014597-66vd2mdu 1583 11 thin thin JJ cord-014597-66vd2mdu 1583 12 layer layer NN cord-014597-66vd2mdu 1583 13 chromatography chromatography NN cord-014597-66vd2mdu 1583 14 ( ( -LRB- cord-014597-66vd2mdu 1583 15 2D 2D NNP cord-014597-66vd2mdu 1583 16 - - HYPH cord-014597-66vd2mdu 1583 17 HPTLC HPTLC NNP cord-014597-66vd2mdu 1583 18 ) ) -RRB- cord-014597-66vd2mdu 1583 19 and and CC cord-014597-66vd2mdu 1583 20 mass mass NN cord-014597-66vd2mdu 1583 21 spectrometry spectrometry NN cord-014597-66vd2mdu 1583 22 ( ( -LRB- cord-014597-66vd2mdu 1583 23 MS MS NNP cord-014597-66vd2mdu 1583 24 ) ) -RRB- cord-014597-66vd2mdu 1583 25 lipid lipid NN cord-014597-66vd2mdu 1583 26 analysis analysis NN cord-014597-66vd2mdu 1583 27 of of IN cord-014597-66vd2mdu 1583 28 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1583 29 , , , cord-014597-66vd2mdu 1583 30 CHO CHO NNP cord-014597-66vd2mdu 1583 31 , , , cord-014597-66vd2mdu 1583 32 and and CC cord-014597-66vd2mdu 1583 33 HEK HEK NNP cord-014597-66vd2mdu 1583 34 cell cell NN cord-014597-66vd2mdu 1583 35 lines line NNS cord-014597-66vd2mdu 1583 36 to to TO cord-014597-66vd2mdu 1583 37 understand understand VB cord-014597-66vd2mdu 1583 38 the the DT cord-014597-66vd2mdu 1583 39 major major JJ cord-014597-66vd2mdu 1583 40 differences difference NNS cord-014597-66vd2mdu 1583 41 in in IN cord-014597-66vd2mdu 1583 42 the the DT cord-014597-66vd2mdu 1583 43 lipid lipid NN cord-014597-66vd2mdu 1583 44 content content NN cord-014597-66vd2mdu 1583 45 of of IN cord-014597-66vd2mdu 1583 46 these these DT cord-014597-66vd2mdu 1583 47 hosts host NNS cord-014597-66vd2mdu 1583 48 . . . cord-014597-66vd2mdu 1584 1 Bligh Bligh NNP cord-014597-66vd2mdu 1584 2 - - HYPH cord-014597-66vd2mdu 1584 3 Dyer Dyer NNP cord-014597-66vd2mdu 1584 4 method method NN cord-014597-66vd2mdu 1584 5 was be VBD cord-014597-66vd2mdu 1584 6 used use VBN cord-014597-66vd2mdu 1584 7 to to TO cord-014597-66vd2mdu 1584 8 extract extract VB cord-014597-66vd2mdu 1584 9 the the DT cord-014597-66vd2mdu 1584 10 lipids lipid NNS cord-014597-66vd2mdu 1584 11 and and CC cord-014597-66vd2mdu 1584 12 extracts extract NNS cord-014597-66vd2mdu 1584 13 were be VBD cord-014597-66vd2mdu 1584 14 analyzed analyze VBN cord-014597-66vd2mdu 1584 15 by by IN cord-014597-66vd2mdu 1584 16 HP HP NNP cord-014597-66vd2mdu 1584 17 - - HYPH cord-014597-66vd2mdu 1584 18 TLC TLC NNP cord-014597-66vd2mdu 1584 19 and and CC cord-014597-66vd2mdu 1584 20 MS MS NNP cord-014597-66vd2mdu 1584 21 . . . cord-014597-66vd2mdu 1585 1 The the DT cord-014597-66vd2mdu 1585 2 polar polar JJ cord-014597-66vd2mdu 1585 3 lipids lipid NNS cord-014597-66vd2mdu 1585 4 were be VBD cord-014597-66vd2mdu 1585 5 separated separate VBN cord-014597-66vd2mdu 1585 6 into into IN cord-014597-66vd2mdu 1585 7 different different JJ cord-014597-66vd2mdu 1585 8 categories category NNS cord-014597-66vd2mdu 1585 9 by by IN cord-014597-66vd2mdu 1585 10 2-D 2-d JJ cord-014597-66vd2mdu 1585 11 HP HP NNP cord-014597-66vd2mdu 1585 12 - - HYPH cord-014597-66vd2mdu 1585 13 TLC TLC NNP cord-014597-66vd2mdu 1585 14 using use VBG cord-014597-66vd2mdu 1585 15 a a DT cord-014597-66vd2mdu 1585 16 CHCl CHCl NNS cord-014597-66vd2mdu 1585 17 3 3 CD cord-014597-66vd2mdu 1585 18 -MeOH -MeOH NNS cord-014597-66vd2mdu 1585 19 - - HYPH cord-014597-66vd2mdu 1585 20 H h NN cord-014597-66vd2mdu 1585 21 2 2 CD cord-014597-66vd2mdu 1585 22 O o NN cord-014597-66vd2mdu 1585 23 ( ( -LRB- cord-014597-66vd2mdu 1585 24 71:25:2.5 71:25:2.5 NNP cord-014597-66vd2mdu 1585 25 , , , cord-014597-66vd2mdu 1585 26 v v NNP cord-014597-66vd2mdu 1585 27 / / SYM cord-014597-66vd2mdu 1585 28 v v NN cord-014597-66vd2mdu 1585 29 / / SYM cord-014597-66vd2mdu 1585 30 v v NN cord-014597-66vd2mdu 1585 31 ) ) -RRB- cord-014597-66vd2mdu 1585 32 solvent solvent NN cord-014597-66vd2mdu 1585 33 system system NN cord-014597-66vd2mdu 1585 34 in in IN cord-014597-66vd2mdu 1585 35 the the DT cord-014597-66vd2mdu 1585 36 first first JJ cord-014597-66vd2mdu 1585 37 dimension dimension NN cord-014597-66vd2mdu 1585 38 and and CC cord-014597-66vd2mdu 1585 39 a a DT cord-014597-66vd2mdu 1585 40 CHCl CHCl NNS cord-014597-66vd2mdu 1585 41 3 3 CD cord-014597-66vd2mdu 1585 42 -MeOH -meoh CD cord-014597-66vd2mdu 1585 43 - - HYPH cord-014597-66vd2mdu 1585 44 Acetic acetic JJ cord-014597-66vd2mdu 1585 45 acid acid NN cord-014597-66vd2mdu 1585 46 - - HYPH cord-014597-66vd2mdu 1585 47 H h NN cord-014597-66vd2mdu 1585 48 2 2 CD cord-014597-66vd2mdu 1585 49 O o NN cord-014597-66vd2mdu 1585 50 ( ( -LRB- cord-014597-66vd2mdu 1585 51 76:9:12:2 76:9:12:2 NNP cord-014597-66vd2mdu 1585 52 , , , cord-014597-66vd2mdu 1585 53 v v NN cord-014597-66vd2mdu 1585 54 / / SYM cord-014597-66vd2mdu 1585 55 v v NN cord-014597-66vd2mdu 1585 56 / / SYM cord-014597-66vd2mdu 1585 57 v v NN cord-014597-66vd2mdu 1585 58 / / SYM cord-014597-66vd2mdu 1585 59 v v NN cord-014597-66vd2mdu 1585 60 ) ) -RRB- cord-014597-66vd2mdu 1585 61 solvent solvent NN cord-014597-66vd2mdu 1585 62 system system NN cord-014597-66vd2mdu 1585 63 in in IN cord-014597-66vd2mdu 1585 64 the the DT cord-014597-66vd2mdu 1585 65 second second JJ cord-014597-66vd2mdu 1585 66 dimension dimension NN cord-014597-66vd2mdu 1585 67 . . . cord-014597-66vd2mdu 1586 1 Non non JJ cord-014597-66vd2mdu 1586 2 - - JJ cord-014597-66vd2mdu 1586 3 polar polar JJ cord-014597-66vd2mdu 1586 4 lipids lipid NNS cord-014597-66vd2mdu 1586 5 were be VBD cord-014597-66vd2mdu 1586 6 separated separate VBN cord-014597-66vd2mdu 1586 7 by by IN cord-014597-66vd2mdu 1586 8 1-D 1-d CD cord-014597-66vd2mdu 1586 9 HPTLC HPTLC NNP cord-014597-66vd2mdu 1586 10 using use VBG cord-014597-66vd2mdu 1586 11 hexane hexane NN cord-014597-66vd2mdu 1586 12 - - HYPH cord-014597-66vd2mdu 1586 13 diethyl diethyl JJ cord-014597-66vd2mdu 1586 14 ether ether NN cord-014597-66vd2mdu 1586 15 - - HYPH cord-014597-66vd2mdu 1586 16 acetic acetic NN cord-014597-66vd2mdu 1586 17 acid acid NN cord-014597-66vd2mdu 1586 18 . . . cord-014597-66vd2mdu 1587 1 2,7-dichlorofluorescein 2,7-dichlorofluorescein CD cord-014597-66vd2mdu 1587 2 dye dye NN cord-014597-66vd2mdu 1587 3 was be VBD cord-014597-66vd2mdu 1587 4 used use VBN cord-014597-66vd2mdu 1587 5 to to TO cord-014597-66vd2mdu 1587 6 visualize visualize VB cord-014597-66vd2mdu 1587 7 both both DT cord-014597-66vd2mdu 1587 8 polar polar JJ cord-014597-66vd2mdu 1587 9 and and CC cord-014597-66vd2mdu 1587 10 non non JJ cord-014597-66vd2mdu 1587 11 - - JJ cord-014597-66vd2mdu 1587 12 polar polar JJ cord-014597-66vd2mdu 1587 13 lipids lipid NNS cord-014597-66vd2mdu 1587 14 . . . cord-014597-66vd2mdu 1588 1 Further further JJ cord-014597-66vd2mdu 1588 2 detailed detailed JJ cord-014597-66vd2mdu 1588 3 analysis analysis NN cord-014597-66vd2mdu 1588 4 was be VBD cord-014597-66vd2mdu 1588 5 performed perform VBN cord-014597-66vd2mdu 1588 6 on on IN cord-014597-66vd2mdu 1588 7 a a DT cord-014597-66vd2mdu 1588 8 QqQ QqQ NNP cord-014597-66vd2mdu 1588 9 mass mass NN cord-014597-66vd2mdu 1588 10 spectrometer spectrometer NN cord-014597-66vd2mdu 1588 11 ( ( -LRB- cord-014597-66vd2mdu 1588 12 Thermo Thermo NNP cord-014597-66vd2mdu 1588 13 TSQ TSQ NNP cord-014597-66vd2mdu 1588 14 VANTAGE VANTAGE NNP cord-014597-66vd2mdu 1588 15 , , , cord-014597-66vd2mdu 1588 16 San San NNP cord-014597-66vd2mdu 1588 17 Jose Jose NNP cord-014597-66vd2mdu 1588 18 , , , cord-014597-66vd2mdu 1588 19 CA CA NNP cord-014597-66vd2mdu 1588 20 ) ) -RRB- cord-014597-66vd2mdu 1588 21 using use VBG cord-014597-66vd2mdu 1588 22 negative negative JJ cord-014597-66vd2mdu 1588 23 - - HYPH cord-014597-66vd2mdu 1588 24 ion ion NN cord-014597-66vd2mdu 1588 25 and and CC cord-014597-66vd2mdu 1588 26 positive positive JJ cord-014597-66vd2mdu 1588 27 - - HYPH cord-014597-66vd2mdu 1588 28 ion ion NN cord-014597-66vd2mdu 1588 29 ESI ESI NNP cord-014597-66vd2mdu 1588 30 modes mode NNS cord-014597-66vd2mdu 1588 31 as as RB cord-014597-66vd2mdu 1588 32 well well RB cord-014597-66vd2mdu 1588 33 as as IN cord-014597-66vd2mdu 1588 34 negative negative JJ cord-014597-66vd2mdu 1588 35 - - HYPH cord-014597-66vd2mdu 1588 36 ion ion NN cord-014597-66vd2mdu 1588 37 ESI ESI NNP cord-014597-66vd2mdu 1588 38 mode mode NN cord-014597-66vd2mdu 1588 39 in in IN cord-014597-66vd2mdu 1588 40 the the DT cord-014597-66vd2mdu 1588 41 presence presence NN cord-014597-66vd2mdu 1588 42 of of IN cord-014597-66vd2mdu 1588 43 lithium lithium NN cord-014597-66vd2mdu 1588 44 hydroxide hydroxide NN cord-014597-66vd2mdu 1588 45 . . . cord-014597-66vd2mdu 1589 1 In in IN cord-014597-66vd2mdu 1589 2 this this DT cord-014597-66vd2mdu 1589 3 study study NN cord-014597-66vd2mdu 1589 4 , , , cord-014597-66vd2mdu 1589 5 quantitative quantitative JJ cord-014597-66vd2mdu 1589 6 lipidomics lipidomic NNS cord-014597-66vd2mdu 1589 7 was be VBD cord-014597-66vd2mdu 1589 8 coupled couple VBN cord-014597-66vd2mdu 1589 9 with with IN cord-014597-66vd2mdu 1589 10 transcriptomics transcriptomic NNS cord-014597-66vd2mdu 1589 11 to to TO cord-014597-66vd2mdu 1589 12 further further RB cord-014597-66vd2mdu 1589 13 understand understand VB cord-014597-66vd2mdu 1589 14 the the DT cord-014597-66vd2mdu 1589 15 physiological physiological JJ cord-014597-66vd2mdu 1589 16 pathways pathway NNS cord-014597-66vd2mdu 1589 17 of of IN cord-014597-66vd2mdu 1589 18 HEK HEK NNP cord-014597-66vd2mdu 1589 19 , , , cord-014597-66vd2mdu 1589 20 CHO CHO NNP cord-014597-66vd2mdu 1589 21 - - HYPH cord-014597-66vd2mdu 1589 22 M M NNP cord-014597-66vd2mdu 1589 23 and and CC cord-014597-66vd2mdu 1589 24 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1589 25 cells cell NNS cord-014597-66vd2mdu 1589 26 . . . cord-014597-66vd2mdu 1590 1 Initial initial JJ cord-014597-66vd2mdu 1590 2 HP HP NNP cord-014597-66vd2mdu 1590 3 - - HYPH cord-014597-66vd2mdu 1590 4 TLC TLC NNP cord-014597-66vd2mdu 1590 5 analysis analysis NN cord-014597-66vd2mdu 1590 6 indicated indicate VBD cord-014597-66vd2mdu 1590 7 that that IN cord-014597-66vd2mdu 1590 8 major major JJ cord-014597-66vd2mdu 1590 9 lipids lipid NNS cord-014597-66vd2mdu 1590 10 in in IN cord-014597-66vd2mdu 1590 11 these these DT cord-014597-66vd2mdu 1590 12 industrial industrial JJ cord-014597-66vd2mdu 1590 13 cell cell NN cord-014597-66vd2mdu 1590 14 lines line NNS cord-014597-66vd2mdu 1590 15 were be VBD cord-014597-66vd2mdu 1590 16 PE PE NNP cord-014597-66vd2mdu 1590 17 and and CC cord-014597-66vd2mdu 1590 18 PC pc NN cord-014597-66vd2mdu 1590 19 . . . cord-014597-66vd2mdu 1591 1 Other other JJ cord-014597-66vd2mdu 1591 2 polar polar JJ cord-014597-66vd2mdu 1591 3 lipids lipid NNS cord-014597-66vd2mdu 1591 4 such such JJ cord-014597-66vd2mdu 1591 5 as as IN cord-014597-66vd2mdu 1591 6 PI PI NNP cord-014597-66vd2mdu 1591 7 , , , cord-014597-66vd2mdu 1591 8 PS PS NNP cord-014597-66vd2mdu 1591 9 , , , cord-014597-66vd2mdu 1591 10 PG PG NNP cord-014597-66vd2mdu 1591 11 , , , cord-014597-66vd2mdu 1591 12 PA PA NNP cord-014597-66vd2mdu 1591 13 , , , cord-014597-66vd2mdu 1591 14 and and CC cord-014597-66vd2mdu 1591 15 SM SM NNP cord-014597-66vd2mdu 1591 16 were be VBD cord-014597-66vd2mdu 1591 17 lower low JJR cord-014597-66vd2mdu 1591 18 compared compare VBN cord-014597-66vd2mdu 1591 19 to to IN cord-014597-66vd2mdu 1591 20 PC pc NN cord-014597-66vd2mdu 1591 21 and and CC cord-014597-66vd2mdu 1591 22 PE PE NNP cord-014597-66vd2mdu 1591 23 in in IN cord-014597-66vd2mdu 1591 24 exponential exponential JJ cord-014597-66vd2mdu 1591 25 and and CC cord-014597-66vd2mdu 1591 26 stationary stationary JJ cord-014597-66vd2mdu 1591 27 phases phase NNS cord-014597-66vd2mdu 1591 28 of of IN cord-014597-66vd2mdu 1591 29 each each DT cord-014597-66vd2mdu 1591 30 cell cell NN cord-014597-66vd2mdu 1591 31 line line NN cord-014597-66vd2mdu 1591 32 . . . cord-014597-66vd2mdu 1592 1 Figure figure NN cord-014597-66vd2mdu 1592 2 1 1 CD cord-014597-66vd2mdu 1592 3 represents represent VBZ cord-014597-66vd2mdu 1592 4 2D 2d JJ cord-014597-66vd2mdu 1592 5 HP HP NNP cord-014597-66vd2mdu 1592 6 - - HYPH cord-014597-66vd2mdu 1592 7 TLC TLC NNP cord-014597-66vd2mdu 1592 8 results result NNS cord-014597-66vd2mdu 1592 9 of of IN cord-014597-66vd2mdu 1592 10 HEK HEK NNP cord-014597-66vd2mdu 1592 11 with with IN cord-014597-66vd2mdu 1592 12 the the DT cord-014597-66vd2mdu 1592 13 relative relative JJ cord-014597-66vd2mdu 1592 14 quantitation quantitation NN cord-014597-66vd2mdu 1592 15 of of IN cord-014597-66vd2mdu 1592 16 polar polar JJ cord-014597-66vd2mdu 1592 17 lipids lipid NNS cord-014597-66vd2mdu 1592 18 . . . cord-014597-66vd2mdu 1593 1 In in IN cord-014597-66vd2mdu 1593 2 order order NN cord-014597-66vd2mdu 1593 3 to to TO cord-014597-66vd2mdu 1593 4 investigate investigate VB cord-014597-66vd2mdu 1593 5 the the DT cord-014597-66vd2mdu 1593 6 lipid lipid NN cord-014597-66vd2mdu 1593 7 subgroups subgroup NNS cord-014597-66vd2mdu 1593 8 , , , cord-014597-66vd2mdu 1593 9 shotgun shotgun NN cord-014597-66vd2mdu 1593 10 MS MS NNP cord-014597-66vd2mdu 1593 11 analysis analysis NN cord-014597-66vd2mdu 1593 12 was be VBD cord-014597-66vd2mdu 1593 13 conducted conduct VBN cord-014597-66vd2mdu 1593 14 for for IN cord-014597-66vd2mdu 1593 15 both both CC cord-014597-66vd2mdu 1593 16 exponential exponential JJ cord-014597-66vd2mdu 1593 17 and and CC cord-014597-66vd2mdu 1593 18 stationary stationary JJ cord-014597-66vd2mdu 1593 19 growth growth NN cord-014597-66vd2mdu 1593 20 phases phase NNS cord-014597-66vd2mdu 1593 21 of of IN cord-014597-66vd2mdu 1593 22 the the DT cord-014597-66vd2mdu 1593 23 three three CD cord-014597-66vd2mdu 1593 24 cell cell NN cord-014597-66vd2mdu 1593 25 lines line NNS cord-014597-66vd2mdu 1593 26 . . . cord-014597-66vd2mdu 1594 1 MS MS NNP cord-014597-66vd2mdu 1594 2 analysis analysis NN cord-014597-66vd2mdu 1594 3 indicated indicate VBD cord-014597-66vd2mdu 1594 4 that that IN cord-014597-66vd2mdu 1594 5 lysophosphatidylethanolamine lysophosphatidylethanolamine NNP cord-014597-66vd2mdu 1594 6 ( ( -LRB- cord-014597-66vd2mdu 1594 7 LPE LPE NNP cord-014597-66vd2mdu 1594 8 ) ) -RRB- cord-014597-66vd2mdu 1594 9 and and CC cord-014597-66vd2mdu 1594 10 lyso lyso NN cord-014597-66vd2mdu 1594 11 - - HYPH cord-014597-66vd2mdu 1594 12 phosphatidylcholine phosphatidylcholine NNP cord-014597-66vd2mdu 1594 13 ( ( -LRB- cord-014597-66vd2mdu 1594 14 LPC LPC NNP cord-014597-66vd2mdu 1594 15 ) ) -RRB- cord-014597-66vd2mdu 1594 16 amounts amount NNS cord-014597-66vd2mdu 1594 17 were be VBD cord-014597-66vd2mdu 1594 18 4 4 CD cord-014597-66vd2mdu 1594 19 -10 -10 NN cord-014597-66vd2mdu 1594 20 fold fold JJ cord-014597-66vd2mdu 1594 21 and and CC cord-014597-66vd2mdu 1594 22 2 2 CD cord-014597-66vd2mdu 1594 23 - - SYM cord-014597-66vd2mdu 1594 24 4 4 CD cord-014597-66vd2mdu 1594 25 fold fold VBP cord-014597-66vd2mdu 1594 26 higher higher RBR cord-014597-66vd2mdu 1594 27 in in IN cord-014597-66vd2mdu 1594 28 HEK HEK NNP cord-014597-66vd2mdu 1594 29 cells cell NNS cord-014597-66vd2mdu 1594 30 compared compare VBN cord-014597-66vd2mdu 1594 31 to to IN cord-014597-66vd2mdu 1594 32 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1594 33 and and CC cord-014597-66vd2mdu 1594 34 CHO CHO NNP cord-014597-66vd2mdu 1594 35 cell cell NN cord-014597-66vd2mdu 1594 36 lines line NNS cord-014597-66vd2mdu 1594 37 . . . cord-014597-66vd2mdu 1595 1 Sphingomyelin Sphingomyelin NNP cord-014597-66vd2mdu 1595 2 ( ( -LRB- cord-014597-66vd2mdu 1595 3 SM SM NNP cord-014597-66vd2mdu 1595 4 ) ) -RRB- cord-014597-66vd2mdu 1595 5 was be VBD cord-014597-66vd2mdu 1595 6 another another DT cord-014597-66vd2mdu 1595 7 lipid lipid NN cord-014597-66vd2mdu 1595 8 subgroup subgroup NN cord-014597-66vd2mdu 1595 9 that that WDT cord-014597-66vd2mdu 1595 10 was be VBD cord-014597-66vd2mdu 1595 11 shown show VBN cord-014597-66vd2mdu 1595 12 to to TO cord-014597-66vd2mdu 1595 13 have have VB cord-014597-66vd2mdu 1595 14 a a DT cord-014597-66vd2mdu 1595 15 major major JJ cord-014597-66vd2mdu 1595 16 difference difference NN cord-014597-66vd2mdu 1595 17 between between IN cord-014597-66vd2mdu 1595 18 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1595 19 and and CC cord-014597-66vd2mdu 1595 20 other other JJ cord-014597-66vd2mdu 1595 21 mammalian mammalian JJ cord-014597-66vd2mdu 1595 22 cell cell NN cord-014597-66vd2mdu 1595 23 lines line NNS cord-014597-66vd2mdu 1595 24 . . . cord-014597-66vd2mdu 1596 1 SM SM NNP cord-014597-66vd2mdu 1596 2 was be VBD cord-014597-66vd2mdu 1596 3 30 30 CD cord-014597-66vd2mdu 1596 4 - - SYM cord-014597-66vd2mdu 1596 5 65 65 CD cord-014597-66vd2mdu 1596 6 fold fold VB cord-014597-66vd2mdu 1596 7 lower lower RBR cord-014597-66vd2mdu 1596 8 in in IN cord-014597-66vd2mdu 1596 9 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1596 10 cell cell NN cord-014597-66vd2mdu 1596 11 line line NN cord-014597-66vd2mdu 1596 12 compared compare VBN cord-014597-66vd2mdu 1596 13 to to IN cord-014597-66vd2mdu 1596 14 CHO CHO NNP cord-014597-66vd2mdu 1596 15 and and CC cord-014597-66vd2mdu 1596 16 HEK HEK NNP cord-014597-66vd2mdu 1596 17 . . . cord-014597-66vd2mdu 1597 1 To to TO cord-014597-66vd2mdu 1597 2 understand understand VB cord-014597-66vd2mdu 1597 3 these these DT cord-014597-66vd2mdu 1597 4 metabolic metabolic JJ cord-014597-66vd2mdu 1597 5 differences difference NNS cord-014597-66vd2mdu 1597 6 , , , cord-014597-66vd2mdu 1597 7 transcriptomics transcriptomic NNS cord-014597-66vd2mdu 1597 8 analysis analysis NN cord-014597-66vd2mdu 1597 9 using use VBG cord-014597-66vd2mdu 1597 10 Illumina Illumina NNP cord-014597-66vd2mdu 1597 11 HighSeq HighSeq NNP cord-014597-66vd2mdu 1597 12 and and CC cord-014597-66vd2mdu 1597 13 Gene Gene NNP cord-014597-66vd2mdu 1597 14 Expression Expression NNP cord-014597-66vd2mdu 1597 15 Omnibus Omnibus NNP cord-014597-66vd2mdu 1597 16 was be VBD cord-014597-66vd2mdu 1597 17 conducted conduct VBN cord-014597-66vd2mdu 1597 18 on on IN cord-014597-66vd2mdu 1597 19 these these DT cord-014597-66vd2mdu 1597 20 mammalian mammalian JJ cord-014597-66vd2mdu 1597 21 cells cell NNS cord-014597-66vd2mdu 1597 22 . . . cord-014597-66vd2mdu 1598 1 The the DT cord-014597-66vd2mdu 1598 2 Kyoto Kyoto NNP cord-014597-66vd2mdu 1598 3 Encyclopedia Encyclopedia NNP cord-014597-66vd2mdu 1598 4 of of IN cord-014597-66vd2mdu 1598 5 Genes Genes NNPS cord-014597-66vd2mdu 1598 6 and and CC cord-014597-66vd2mdu 1598 7 Genomes Genomes NNPS cord-014597-66vd2mdu 1598 8 ( ( -LRB- cord-014597-66vd2mdu 1598 9 KEGG KEGG NNP cord-014597-66vd2mdu 1598 10 ) ) -RRB- cord-014597-66vd2mdu 1598 11 database database NN cord-014597-66vd2mdu 1598 12 was be VBD cord-014597-66vd2mdu 1598 13 used use VBN cord-014597-66vd2mdu 1598 14 to to TO cord-014597-66vd2mdu 1598 15 map map VB cord-014597-66vd2mdu 1598 16 the the DT cord-014597-66vd2mdu 1598 17 transcriptomics transcriptomics NNP cord-014597-66vd2mdu 1598 18 data datum NNS cord-014597-66vd2mdu 1598 19 to to IN cord-014597-66vd2mdu 1598 20 the the DT cord-014597-66vd2mdu 1598 21 lipid lipid NN cord-014597-66vd2mdu 1598 22 synthetic synthetic JJ cord-014597-66vd2mdu 1598 23 pathways pathway NNS cord-014597-66vd2mdu 1598 24 . . . cord-014597-66vd2mdu 1599 1 Transcriptomics Transcriptomics NNP cord-014597-66vd2mdu 1599 2 data data NN cord-014597-66vd2mdu 1599 3 mapping mapping NN cord-014597-66vd2mdu 1599 4 to to IN cord-014597-66vd2mdu 1599 5 KEGG KEGG NNP cord-014597-66vd2mdu 1599 6 pathways pathway NNS cord-014597-66vd2mdu 1599 7 demonstrated demonstrate VBD cord-014597-66vd2mdu 1599 8 that that IN cord-014597-66vd2mdu 1599 9 differences difference NNS cord-014597-66vd2mdu 1599 10 in in IN cord-014597-66vd2mdu 1599 11 LPE LPE NNP cord-014597-66vd2mdu 1599 12 and and CC cord-014597-66vd2mdu 1599 13 LPC LPC NNP cord-014597-66vd2mdu 1599 14 pathways pathway NNS cord-014597-66vd2mdu 1599 15 correlate correlate VBP cord-014597-66vd2mdu 1599 16 with with IN cord-014597-66vd2mdu 1599 17 the the DT cord-014597-66vd2mdu 1599 18 expression expression NN cord-014597-66vd2mdu 1599 19 profiles profile NNS cord-014597-66vd2mdu 1599 20 of of IN cord-014597-66vd2mdu 1599 21 secretory secretory JJ cord-014597-66vd2mdu 1599 22 phospholipase phospholipase NN cord-014597-66vd2mdu 1599 23 A2 A2 NNP cord-014597-66vd2mdu 1599 24 ( ( -LRB- cord-014597-66vd2mdu 1599 25 sPLA2 sPLA2 NNP cord-014597-66vd2mdu 1599 26 ) ) -RRB- cord-014597-66vd2mdu 1599 27 , , , cord-014597-66vd2mdu 1599 28 lysophospholipid lysophospholipid NNP cord-014597-66vd2mdu 1599 29 acyltransferase acyltransferase NNP cord-014597-66vd2mdu 1599 30 ( ( -LRB- cord-014597-66vd2mdu 1599 31 LPEAT LPEAT NNP cord-014597-66vd2mdu 1599 32 ) ) -RRB- cord-014597-66vd2mdu 1599 33 , , , cord-014597-66vd2mdu 1599 34 lysophosphatidylcholine lysophosphatidylcholine NNP cord-014597-66vd2mdu 1599 35 acyltransferase acyltransferase NNP cord-014597-66vd2mdu 1599 36 ( ( -LRB- cord-014597-66vd2mdu 1599 37 LPCAT LPCAT NNP cord-014597-66vd2mdu 1599 38 ) ) -RRB- cord-014597-66vd2mdu 1599 39 , , , cord-014597-66vd2mdu 1599 40 and and CC cord-014597-66vd2mdu 1599 41 lysophospholipase lysophospholipase NNP cord-014597-66vd2mdu 1599 42 ( ( -LRB- cord-014597-66vd2mdu 1599 43 LYPLA LYPLA NNP cord-014597-66vd2mdu 1599 44 ) ) -RRB- cord-014597-66vd2mdu 1600 1 [ [ -LRB- cord-014597-66vd2mdu 1600 2 1 1 CD cord-014597-66vd2mdu 1600 3 ] ] -RRB- cord-014597-66vd2mdu 1600 4 . . . cord-014597-66vd2mdu 1601 1 The the DT cord-014597-66vd2mdu 1601 2 HP HP NNP cord-014597-66vd2mdu 1601 3 - - HYPH cord-014597-66vd2mdu 1601 4 TLC TLC NNP cord-014597-66vd2mdu 1601 5 and and CC cord-014597-66vd2mdu 1601 6 LC LC NNP cord-014597-66vd2mdu 1601 7 / / SYM cord-014597-66vd2mdu 1601 8 MS MS NNP cord-014597-66vd2mdu 1601 9 findings finding NNS cord-014597-66vd2mdu 1601 10 demonstrated demonstrate VBD cord-014597-66vd2mdu 1601 11 that that IN cord-014597-66vd2mdu 1601 12 high high JJ cord-014597-66vd2mdu 1601 13 levels level NNS cord-014597-66vd2mdu 1601 14 of of IN cord-014597-66vd2mdu 1601 15 LPE LPE NNP cord-014597-66vd2mdu 1601 16 and and CC cord-014597-66vd2mdu 1601 17 LPC LPC NNP cord-014597-66vd2mdu 1601 18 existed exist VBD cord-014597-66vd2mdu 1601 19 in in IN cord-014597-66vd2mdu 1601 20 the the DT cord-014597-66vd2mdu 1601 21 HEK HEK NNP cord-014597-66vd2mdu 1601 22 cell cell NN cord-014597-66vd2mdu 1601 23 line line NN cord-014597-66vd2mdu 1601 24 and and CC cord-014597-66vd2mdu 1601 25 low low JJ cord-014597-66vd2mdu 1601 26 levels level NNS cord-014597-66vd2mdu 1601 27 of of IN cord-014597-66vd2mdu 1601 28 SM SM NNP cord-014597-66vd2mdu 1601 29 were be VBD cord-014597-66vd2mdu 1601 30 observed observe VBN cord-014597-66vd2mdu 1601 31 in in IN cord-014597-66vd2mdu 1601 32 the the DT cord-014597-66vd2mdu 1601 33 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1601 34 cell cell NN cord-014597-66vd2mdu 1601 35 line line NN cord-014597-66vd2mdu 1601 36 . . . cord-014597-66vd2mdu 1602 1 Coupling couple VBG cord-014597-66vd2mdu 1602 2 lipidomics lipidomic NNS cord-014597-66vd2mdu 1602 3 with with IN cord-014597-66vd2mdu 1602 4 transcriptomics transcriptomic NNS cord-014597-66vd2mdu 1602 5 provides provide VBZ cord-014597-66vd2mdu 1602 6 us -PRON- PRP cord-014597-66vd2mdu 1602 7 with with IN cord-014597-66vd2mdu 1602 8 an an DT cord-014597-66vd2mdu 1602 9 improved improved JJ cord-014597-66vd2mdu 1602 10 understanding understanding NN cord-014597-66vd2mdu 1602 11 of of IN cord-014597-66vd2mdu 1602 12 the the DT cord-014597-66vd2mdu 1602 13 physiological physiological JJ cord-014597-66vd2mdu 1602 14 differences difference NNS cord-014597-66vd2mdu 1602 15 across across IN cord-014597-66vd2mdu 1602 16 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 1602 17 , , , cord-014597-66vd2mdu 1602 18 CHO CHO NNP cord-014597-66vd2mdu 1602 19 , , , cord-014597-66vd2mdu 1602 20 and and CC cord-014597-66vd2mdu 1602 21 HEK HEK NNP cord-014597-66vd2mdu 1602 22 cell cell NN cord-014597-66vd2mdu 1602 23 lines line NNS cord-014597-66vd2mdu 1602 24 that that WDT cord-014597-66vd2mdu 1602 25 could could MD cord-014597-66vd2mdu 1602 26 be be VB cord-014597-66vd2mdu 1602 27 used use VBN cord-014597-66vd2mdu 1602 28 to to TO cord-014597-66vd2mdu 1602 29 guide guide VB cord-014597-66vd2mdu 1602 30 cell cell NN cord-014597-66vd2mdu 1602 31 engineering engineering NN cord-014597-66vd2mdu 1602 32 efforts effort NNS cord-014597-66vd2mdu 1602 33 with with IN cord-014597-66vd2mdu 1602 34 the the DT cord-014597-66vd2mdu 1602 35 goal goal NN cord-014597-66vd2mdu 1602 36 of of IN cord-014597-66vd2mdu 1602 37 increasing increase VBG cord-014597-66vd2mdu 1602 38 the the DT cord-014597-66vd2mdu 1602 39 recombinant recombinant JJ cord-014597-66vd2mdu 1602 40 protein protein NN cord-014597-66vd2mdu 1602 41 expression expression NN cord-014597-66vd2mdu 1602 42 capabilities capability NNS cord-014597-66vd2mdu 1602 43 of of IN cord-014597-66vd2mdu 1602 44 these these DT cord-014597-66vd2mdu 1602 45 three three CD cord-014597-66vd2mdu 1602 46 cell cell NN cord-014597-66vd2mdu 1602 47 lines line NNS cord-014597-66vd2mdu 1602 48 . . . cord-014597-66vd2mdu 1603 1 Biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 1603 2 are be VBP cord-014597-66vd2mdu 1603 3 a a DT cord-014597-66vd2mdu 1603 4 class class NN cord-014597-66vd2mdu 1603 5 of of IN cord-014597-66vd2mdu 1603 6 biological biological JJ cord-014597-66vd2mdu 1603 7 macromolecules macromolecule NNS cord-014597-66vd2mdu 1603 8 that that WDT cord-014597-66vd2mdu 1603 9 include include VBP cord-014597-66vd2mdu 1603 10 antibodies antibody NNS cord-014597-66vd2mdu 1603 11 and and CC cord-014597-66vd2mdu 1603 12 antibody antibody NN cord-014597-66vd2mdu 1603 13 derivatives derivative NNS cord-014597-66vd2mdu 1603 14 , , , cord-014597-66vd2mdu 1603 15 generally generally RB cord-014597-66vd2mdu 1603 16 produced produce VBN cord-014597-66vd2mdu 1603 17 from from IN cord-014597-66vd2mdu 1603 18 cultured cultured JJ cord-014597-66vd2mdu 1603 19 mammalian mammalian JJ cord-014597-66vd2mdu 1603 20 cell cell NN cord-014597-66vd2mdu 1603 21 lines line NNS cord-014597-66vd2mdu 1603 22 via via IN cord-014597-66vd2mdu 1603 23 secretion secretion NN cord-014597-66vd2mdu 1603 24 directly directly RB cord-014597-66vd2mdu 1603 25 into into IN cord-014597-66vd2mdu 1603 26 the the DT cord-014597-66vd2mdu 1603 27 media medium NNS cord-014597-66vd2mdu 1603 28 . . . cord-014597-66vd2mdu 1604 1 Manufacturing manufacture VBG cord-014597-66vd2mdu 1604 2 at at IN cord-014597-66vd2mdu 1604 3 MedImmune MedImmune NNP cord-014597-66vd2mdu 1604 4 requires require VBZ cord-014597-66vd2mdu 1604 5 the the DT cord-014597-66vd2mdu 1604 6 generation generation NN cord-014597-66vd2mdu 1604 7 of of IN cord-014597-66vd2mdu 1604 8 Chinese chinese JJ cord-014597-66vd2mdu 1604 9 hamster hamster NN cord-014597-66vd2mdu 1604 10 ovary ovary NN cord-014597-66vd2mdu 1604 11 ( ( -LRB- cord-014597-66vd2mdu 1604 12 CHO CHO NNP cord-014597-66vd2mdu 1604 13 ) ) -RRB- cord-014597-66vd2mdu 1604 14 clonal clonal JJ cord-014597-66vd2mdu 1604 15 cell cell NN cord-014597-66vd2mdu 1604 16 lines line NNS cord-014597-66vd2mdu 1604 17 capable capable JJ cord-014597-66vd2mdu 1604 18 of of IN cord-014597-66vd2mdu 1604 19 producing produce VBG cord-014597-66vd2mdu 1604 20 the the DT cord-014597-66vd2mdu 1604 21 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 1604 22 product product NN cord-014597-66vd2mdu 1604 23 at at IN cord-014597-66vd2mdu 1604 24 commercially commercially RB cord-014597-66vd2mdu 1604 25 relevant relevant JJ cord-014597-66vd2mdu 1604 26 quantities quantity NNS cord-014597-66vd2mdu 1604 27 with with IN cord-014597-66vd2mdu 1604 28 optimal optimal JJ cord-014597-66vd2mdu 1604 29 product product NN cord-014597-66vd2mdu 1604 30 quality quality NN cord-014597-66vd2mdu 1604 31 . . . cord-014597-66vd2mdu 1605 1 The the DT cord-014597-66vd2mdu 1605 2 isolation isolation NN cord-014597-66vd2mdu 1605 3 of of IN cord-014597-66vd2mdu 1605 4 cell cell NN cord-014597-66vd2mdu 1605 5 clones clone NNS cord-014597-66vd2mdu 1605 6 based base VBN cord-014597-66vd2mdu 1605 7 on on IN cord-014597-66vd2mdu 1605 8 random random JJ cord-014597-66vd2mdu 1605 9 single single JJ cord-014597-66vd2mdu 1605 10 cell cell NN cord-014597-66vd2mdu 1605 11 deposition deposition NN cord-014597-66vd2mdu 1605 12 via via IN cord-014597-66vd2mdu 1605 13 fluorescence fluorescence NN cord-014597-66vd2mdu 1605 14 activated activate VBN cord-014597-66vd2mdu 1605 15 cell cell NN cord-014597-66vd2mdu 1605 16 sorting sorting NN cord-014597-66vd2mdu 1605 17 ( ( -LRB- cord-014597-66vd2mdu 1605 18 FACS FACS NNP cord-014597-66vd2mdu 1605 19 ) ) -RRB- cord-014597-66vd2mdu 1605 20 provides provide VBZ cord-014597-66vd2mdu 1605 21 a a DT cord-014597-66vd2mdu 1605 22 heterogeneous heterogeneous JJ cord-014597-66vd2mdu 1605 23 panel panel NN cord-014597-66vd2mdu 1605 24 of of IN cord-014597-66vd2mdu 1605 25 expressers expresser NNS cord-014597-66vd2mdu 1605 26 . . . cord-014597-66vd2mdu 1606 1 We -PRON- PRP cord-014597-66vd2mdu 1606 2 hypothesize hypothesize VBP cord-014597-66vd2mdu 1606 3 that that IN cord-014597-66vd2mdu 1606 4 the the DT cord-014597-66vd2mdu 1606 5 application application NN cord-014597-66vd2mdu 1606 6 of of IN cord-014597-66vd2mdu 1606 7 FACS FACS NNP cord-014597-66vd2mdu 1606 8 to to TO cord-014597-66vd2mdu 1606 9 provide provide VB cord-014597-66vd2mdu 1606 10 an an DT cord-014597-66vd2mdu 1606 11 additional additional JJ cord-014597-66vd2mdu 1606 12 sorting sorting NN cord-014597-66vd2mdu 1606 13 step step NN cord-014597-66vd2mdu 1606 14 based base VBN cord-014597-66vd2mdu 1606 15 on on IN cord-014597-66vd2mdu 1606 16 desirable desirable JJ cord-014597-66vd2mdu 1606 17 cell cell NN cord-014597-66vd2mdu 1606 18 attributes attribute NNS cord-014597-66vd2mdu 1606 19 that that WDT cord-014597-66vd2mdu 1606 20 correlate correlate VBP cord-014597-66vd2mdu 1606 21 with with IN cord-014597-66vd2mdu 1606 22 productivity productivity NN cord-014597-66vd2mdu 1606 23 , , , cord-014597-66vd2mdu 1606 24 product product NN cord-014597-66vd2mdu 1606 25 quality quality NN cord-014597-66vd2mdu 1606 26 or or CC cord-014597-66vd2mdu 1606 27 cell cell NN cord-014597-66vd2mdu 1606 28 growth growth NN cord-014597-66vd2mdu 1606 29 attributes attribute NNS cord-014597-66vd2mdu 1606 30 could could MD cord-014597-66vd2mdu 1606 31 lead lead VB cord-014597-66vd2mdu 1606 32 to to IN cord-014597-66vd2mdu 1606 33 the the DT cord-014597-66vd2mdu 1606 34 isolation isolation NN cord-014597-66vd2mdu 1606 35 of of IN cord-014597-66vd2mdu 1606 36 higher high JJR cord-014597-66vd2mdu 1606 37 producing produce VBG cord-014597-66vd2mdu 1606 38 cell cell NN cord-014597-66vd2mdu 1606 39 lines line NNS cord-014597-66vd2mdu 1606 40 with with IN cord-014597-66vd2mdu 1606 41 enhanced enhanced JJ cord-014597-66vd2mdu 1606 42 product product NN cord-014597-66vd2mdu 1606 43 quality quality NN cord-014597-66vd2mdu 1606 44 attributes attribute NNS cord-014597-66vd2mdu 1606 45 . . . cord-014597-66vd2mdu 1607 1 A a DT cord-014597-66vd2mdu 1607 2 panel panel NN cord-014597-66vd2mdu 1607 3 of of IN cord-014597-66vd2mdu 1607 4 20 20 CD cord-014597-66vd2mdu 1607 5 cell cell NN cord-014597-66vd2mdu 1607 6 lines line NNS cord-014597-66vd2mdu 1607 7 expressing express VBG cord-014597-66vd2mdu 1607 8 a a DT cord-014597-66vd2mdu 1607 9 model model NN cord-014597-66vd2mdu 1607 10 recombinant recombinant JJ cord-014597-66vd2mdu 1607 11 monoclonal monoclonal JJ cord-014597-66vd2mdu 1607 12 antibody antibody NN cord-014597-66vd2mdu 1607 13 were be VBD cord-014597-66vd2mdu 1607 14 characterised characterise VBN cord-014597-66vd2mdu 1607 15 in in IN cord-014597-66vd2mdu 1607 16 terms term NNS cord-014597-66vd2mdu 1607 17 of of IN cord-014597-66vd2mdu 1607 18 growth growth NN cord-014597-66vd2mdu 1607 19 , , , cord-014597-66vd2mdu 1607 20 productivity productivity NN cord-014597-66vd2mdu 1607 21 , , , cord-014597-66vd2mdu 1607 22 intracellular intracellular JJ cord-014597-66vd2mdu 1607 23 recombinant recombinant JJ cord-014597-66vd2mdu 1607 24 protein protein NN cord-014597-66vd2mdu 1607 25 and and CC cord-014597-66vd2mdu 1607 26 mRNA mrna NN cord-014597-66vd2mdu 1607 27 amounts amount NNS cord-014597-66vd2mdu 1607 28 . . . cord-014597-66vd2mdu 1608 1 Assays assay NNS cord-014597-66vd2mdu 1608 2 were be VBD cord-014597-66vd2mdu 1608 3 also also RB cord-014597-66vd2mdu 1608 4 developed develop VBN cord-014597-66vd2mdu 1608 5 to to TO cord-014597-66vd2mdu 1608 6 investigate investigate VB cord-014597-66vd2mdu 1608 7 cell cell NN cord-014597-66vd2mdu 1608 8 attributes attribute NNS cord-014597-66vd2mdu 1608 9 using use VBG cord-014597-66vd2mdu 1608 10 the the DT cord-014597-66vd2mdu 1608 11 commercially commercially RB cord-014597-66vd2mdu 1608 12 available available JJ cord-014597-66vd2mdu 1608 13 ImageStream ImageStream NNP cord-014597-66vd2mdu 1608 14 instrument instrument NN cord-014597-66vd2mdu 1608 15 , , , cord-014597-66vd2mdu 1608 16 an an DT cord-014597-66vd2mdu 1608 17 imaging imaging NN cord-014597-66vd2mdu 1608 18 flow flow NN cord-014597-66vd2mdu 1608 19 cytometer cytometer NN cord-014597-66vd2mdu 1608 20 , , , cord-014597-66vd2mdu 1608 21 which which WDT cord-014597-66vd2mdu 1608 22 enables enable VBZ cord-014597-66vd2mdu 1608 23 the the DT cord-014597-66vd2mdu 1608 24 investigation investigation NN cord-014597-66vd2mdu 1608 25 of of IN cord-014597-66vd2mdu 1608 26 cellular cellular JJ cord-014597-66vd2mdu 1608 27 characteristics characteristic NNS cord-014597-66vd2mdu 1608 28 that that WDT cord-014597-66vd2mdu 1608 29 correlate correlate VBP cord-014597-66vd2mdu 1608 30 with with IN cord-014597-66vd2mdu 1608 31 cell cell NN cord-014597-66vd2mdu 1608 32 productivity productivity NN cord-014597-66vd2mdu 1608 33 at at IN cord-014597-66vd2mdu 1608 34 the the DT cord-014597-66vd2mdu 1608 35 single single JJ cord-014597-66vd2mdu 1608 36 cell cell NN cord-014597-66vd2mdu 1608 37 level level NN cord-014597-66vd2mdu 1608 38 . . . cord-014597-66vd2mdu 1609 1 Characterisation Characterisation NNP cord-014597-66vd2mdu 1609 2 revealed reveal VBD cord-014597-66vd2mdu 1609 3 the the DT cord-014597-66vd2mdu 1609 4 cell cell NN cord-014597-66vd2mdu 1609 5 lines line NNS cord-014597-66vd2mdu 1609 6 exhibited exhibit VBD cord-014597-66vd2mdu 1609 7 a a DT cord-014597-66vd2mdu 1609 8 range range NN cord-014597-66vd2mdu 1609 9 of of IN cord-014597-66vd2mdu 1609 10 values value NNS cord-014597-66vd2mdu 1609 11 for for IN cord-014597-66vd2mdu 1609 12 productivity productivity NN cord-014597-66vd2mdu 1609 13 , , , cord-014597-66vd2mdu 1609 14 growth growth NN cord-014597-66vd2mdu 1609 15 , , , cord-014597-66vd2mdu 1609 16 and and CC cord-014597-66vd2mdu 1609 17 intracellular intracellular JJ cord-014597-66vd2mdu 1609 18 ( ( -LRB- cord-014597-66vd2mdu 1609 19 IC IC NNP cord-014597-66vd2mdu 1609 20 ) ) -RRB- cord-014597-66vd2mdu 1609 21 antibody antibody NN cord-014597-66vd2mdu 1609 22 mRNA mRNA NNP cord-014597-66vd2mdu 1609 23 and and CC cord-014597-66vd2mdu 1609 24 protein protein NN cord-014597-66vd2mdu 1609 25 expression expression NN cord-014597-66vd2mdu 1609 26 , , , cord-014597-66vd2mdu 1609 27 ideal ideal JJ cord-014597-66vd2mdu 1609 28 for for IN cord-014597-66vd2mdu 1609 29 further further JJ cord-014597-66vd2mdu 1609 30 ImageStream ImageStream NNP cord-014597-66vd2mdu 1609 31 characterisation characterisation NN cord-014597-66vd2mdu 1609 32 . . . cord-014597-66vd2mdu 1610 1 Western western JJ cord-014597-66vd2mdu 1610 2 blot blot NN cord-014597-66vd2mdu 1610 3 and and CC cord-014597-66vd2mdu 1610 4 qRT qRT NNP cord-014597-66vd2mdu 1610 5 - - HYPH cord-014597-66vd2mdu 1610 6 PCR PCR NNP cord-014597-66vd2mdu 1610 7 analysis analysis NN cord-014597-66vd2mdu 1610 8 demonstrated demonstrate VBD cord-014597-66vd2mdu 1610 9 that that IN cord-014597-66vd2mdu 1610 10 final final JJ cord-014597-66vd2mdu 1610 11 titre titre NN cord-014597-66vd2mdu 1610 12 correlated correlate VBN cord-014597-66vd2mdu 1610 13 with with IN cord-014597-66vd2mdu 1610 14 both both DT cord-014597-66vd2mdu 1610 15 IC IC NNP cord-014597-66vd2mdu 1610 16 heavy heavy JJ cord-014597-66vd2mdu 1610 17 chain chain NN cord-014597-66vd2mdu 1611 1 ( ( -LRB- cord-014597-66vd2mdu 1611 2 HC HC NNP cord-014597-66vd2mdu 1611 3 ) ) -RRB- cord-014597-66vd2mdu 1611 4 protein protein NNP cord-014597-66vd2mdu 1611 5 and and CC cord-014597-66vd2mdu 1611 6 mRNA mrna NN cord-014597-66vd2mdu 1611 7 amounts amount NNS cord-014597-66vd2mdu 1611 8 ( ( -LRB- cord-014597-66vd2mdu 1611 9 Pearson Pearson NNP cord-014597-66vd2mdu 1611 10 Correlation Correlation NNP cord-014597-66vd2mdu 1611 11 Coefficient Coefficient NNP cord-014597-66vd2mdu 1611 12 ( ( -LRB- cord-014597-66vd2mdu 1611 13 PCC PCC NNP cord-014597-66vd2mdu 1611 14 ) ) -RRB- cord-014597-66vd2mdu 1611 15 = = SYM cord-014597-66vd2mdu 1611 16 0.70 0.70 CD cord-014597-66vd2mdu 1611 17 and and CC cord-014597-66vd2mdu 1611 18 PCC PCC NNP cord-014597-66vd2mdu 1611 19 = = SYM cord-014597-66vd2mdu 1611 20 0.80 0.80 CD cord-014597-66vd2mdu 1611 21 , , , cord-014597-66vd2mdu 1611 22 respectively respectively RB cord-014597-66vd2mdu 1611 23 ) ) -RRB- cord-014597-66vd2mdu 1611 24 . . . cord-014597-66vd2mdu 1612 1 To to TO cord-014597-66vd2mdu 1612 2 assess assess VB cord-014597-66vd2mdu 1612 3 productivity productivity NN cord-014597-66vd2mdu 1612 4 at at IN cord-014597-66vd2mdu 1612 5 the the DT cord-014597-66vd2mdu 1612 6 single single JJ cord-014597-66vd2mdu 1612 7 cell cell NN cord-014597-66vd2mdu 1612 8 level level NN cord-014597-66vd2mdu 1612 9 , , , cord-014597-66vd2mdu 1612 10 assays assay NNS cord-014597-66vd2mdu 1612 11 multiplexing multiplexe VBG cord-014597-66vd2mdu 1612 12 IC IC NNP cord-014597-66vd2mdu 1612 13 HC HC NNP cord-014597-66vd2mdu 1612 14 protein protein NN cord-014597-66vd2mdu 1612 15 and and CC cord-014597-66vd2mdu 1612 16 mRNA mrna NN cord-014597-66vd2mdu 1612 17 with with IN cord-014597-66vd2mdu 1612 18 cell cell NN cord-014597-66vd2mdu 1612 19 attributes attribute NNS cord-014597-66vd2mdu 1612 20 were be VBD cord-014597-66vd2mdu 1612 21 therefore therefore RB cord-014597-66vd2mdu 1612 22 developed develop VBN cord-014597-66vd2mdu 1612 23 . . . cord-014597-66vd2mdu 1613 1 Initial initial JJ cord-014597-66vd2mdu 1613 2 assay assay NN cord-014597-66vd2mdu 1613 3 development development NN cord-014597-66vd2mdu 1613 4 focusing focus VBG cord-014597-66vd2mdu 1613 5 on on IN cord-014597-66vd2mdu 1613 6 HC HC NNP cord-014597-66vd2mdu 1613 7 mRNA mRNA NNP cord-014597-66vd2mdu 1613 8 and and CC cord-014597-66vd2mdu 1613 9 protein protein NN cord-014597-66vd2mdu 1613 10 amounts amount NNS cord-014597-66vd2mdu 1613 11 has have VBZ cord-014597-66vd2mdu 1613 12 revealed reveal VBN cord-014597-66vd2mdu 1613 13 interesting interesting JJ cord-014597-66vd2mdu 1613 14 results result NNS cord-014597-66vd2mdu 1613 15 ; ; : cord-014597-66vd2mdu 1613 16 four four CD cord-014597-66vd2mdu 1613 17 cell cell NN cord-014597-66vd2mdu 1613 18 lines line NNS cord-014597-66vd2mdu 1613 19 displayed display VBD cord-014597-66vd2mdu 1613 20 two two CD cord-014597-66vd2mdu 1613 21 distinct distinct JJ cord-014597-66vd2mdu 1613 22 populations population NNS cord-014597-66vd2mdu 1613 23 , , , cord-014597-66vd2mdu 1613 24 one one CD cord-014597-66vd2mdu 1613 25 producing produce VBG cord-014597-66vd2mdu 1613 26 the the DT cord-014597-66vd2mdu 1613 27 antibody antibody NN cord-014597-66vd2mdu 1613 28 and and CC cord-014597-66vd2mdu 1613 29 another another DT cord-014597-66vd2mdu 1613 30 nonexpressing nonexpressing NN cord-014597-66vd2mdu 1613 31 population population NN cord-014597-66vd2mdu 1613 32 . . . cord-014597-66vd2mdu 1614 1 The the DT cord-014597-66vd2mdu 1614 2 ratio ratio NN cord-014597-66vd2mdu 1614 3 of of IN cord-014597-66vd2mdu 1614 4 these these DT cord-014597-66vd2mdu 1614 5 populations population NNS cord-014597-66vd2mdu 1614 6 varied varied JJ cord-014597-66vd2mdu 1614 7 amongst amongst IN cord-014597-66vd2mdu 1614 8 the the DT cord-014597-66vd2mdu 1614 9 cell cell NN cord-014597-66vd2mdu 1614 10 lines line NNS cord-014597-66vd2mdu 1614 11 . . . cord-014597-66vd2mdu 1615 1 Images image NNS cord-014597-66vd2mdu 1615 2 obtained obtain VBN cord-014597-66vd2mdu 1615 3 from from IN cord-014597-66vd2mdu 1615 4 the the DT cord-014597-66vd2mdu 1615 5 ImageStream ImageStream NNP cord-014597-66vd2mdu 1615 6 have have VBP cord-014597-66vd2mdu 1615 7 shown show VBN cord-014597-66vd2mdu 1615 8 the the DT cord-014597-66vd2mdu 1615 9 cellular cellular JJ cord-014597-66vd2mdu 1615 10 localization localization NN cord-014597-66vd2mdu 1615 11 and and CC cord-014597-66vd2mdu 1615 12 expression expression NN cord-014597-66vd2mdu 1615 13 of of IN cord-014597-66vd2mdu 1615 14 HC HC NNP cord-014597-66vd2mdu 1615 15 and and CC cord-014597-66vd2mdu 1615 16 LC LC NNP cord-014597-66vd2mdu 1615 17 message message NN cord-014597-66vd2mdu 1615 18 and and CC cord-014597-66vd2mdu 1615 19 protein protein NN cord-014597-66vd2mdu 1615 20 ( ( -LRB- cord-014597-66vd2mdu 1615 21 Fig Fig NNP cord-014597-66vd2mdu 1615 22 . . . cord-014597-66vd2mdu 1615 23 1 1 CD cord-014597-66vd2mdu 1615 24 ) ) -RRB- cord-014597-66vd2mdu 1615 25 . . . cord-014597-66vd2mdu 1616 1 For for IN cord-014597-66vd2mdu 1616 2 both both DT cord-014597-66vd2mdu 1616 3 message message NN cord-014597-66vd2mdu 1616 4 and and CC cord-014597-66vd2mdu 1616 5 protein protein NN cord-014597-66vd2mdu 1616 6 , , , cord-014597-66vd2mdu 1616 7 HC HC NNP cord-014597-66vd2mdu 1616 8 and and CC cord-014597-66vd2mdu 1616 9 LC LC NNP cord-014597-66vd2mdu 1616 10 colocalize colocalize NN cord-014597-66vd2mdu 1616 11 in in IN cord-014597-66vd2mdu 1616 12 the the DT cord-014597-66vd2mdu 1616 13 cell cell NN cord-014597-66vd2mdu 1616 14 . . . cord-014597-66vd2mdu 1617 1 Whether whether IN cord-014597-66vd2mdu 1617 2 there there EX cord-014597-66vd2mdu 1617 3 is be VBZ cord-014597-66vd2mdu 1617 4 any any DT cord-014597-66vd2mdu 1617 5 relationship relationship NN cord-014597-66vd2mdu 1617 6 between between IN cord-014597-66vd2mdu 1617 7 IC IC NNP cord-014597-66vd2mdu 1617 8 HC HC NNP cord-014597-66vd2mdu 1617 9 protein protein NN cord-014597-66vd2mdu 1617 10 and and CC cord-014597-66vd2mdu 1617 11 cell cell NN cord-014597-66vd2mdu 1617 12 attributes attribute NNS cord-014597-66vd2mdu 1617 13 at at IN cord-014597-66vd2mdu 1617 14 the the DT cord-014597-66vd2mdu 1617 15 single single JJ cord-014597-66vd2mdu 1617 16 cell cell NN cord-014597-66vd2mdu 1617 17 level level NN cord-014597-66vd2mdu 1617 18 was be VBD cord-014597-66vd2mdu 1617 19 then then RB cord-014597-66vd2mdu 1617 20 also also RB cord-014597-66vd2mdu 1617 21 investigated investigate VBN cord-014597-66vd2mdu 1617 22 , , , cord-014597-66vd2mdu 1617 23 as as RB cord-014597-66vd2mdu 1617 24 well well RB cord-014597-66vd2mdu 1617 25 as as IN cord-014597-66vd2mdu 1617 26 correlations correlation NNS cord-014597-66vd2mdu 1617 27 with with IN cord-014597-66vd2mdu 1617 28 cell cell NN cord-014597-66vd2mdu 1617 29 culture culture NN cord-014597-66vd2mdu 1617 30 parameters parameter NNS cord-014597-66vd2mdu 1617 31 at at IN cord-014597-66vd2mdu 1617 32 the the DT cord-014597-66vd2mdu 1617 33 population population NN cord-014597-66vd2mdu 1617 34 level level NN cord-014597-66vd2mdu 1617 35 . . . cord-014597-66vd2mdu 1618 1 At at IN cord-014597-66vd2mdu 1618 2 the the DT cord-014597-66vd2mdu 1618 3 population population NN cord-014597-66vd2mdu 1618 4 level level NN cord-014597-66vd2mdu 1618 5 , , , cord-014597-66vd2mdu 1618 6 correlations correlation NNS cord-014597-66vd2mdu 1618 7 were be VBD cord-014597-66vd2mdu 1618 8 found find VBN cord-014597-66vd2mdu 1618 9 between between IN cord-014597-66vd2mdu 1618 10 titre titre NN cord-014597-66vd2mdu 1618 11 and and CC cord-014597-66vd2mdu 1618 12 IC IC NNP cord-014597-66vd2mdu 1618 13 HC HC NNP cord-014597-66vd2mdu 1618 14 protein protein NN cord-014597-66vd2mdu 1618 15 and and CC cord-014597-66vd2mdu 1618 16 mRNA mRNA NNP cord-014597-66vd2mdu 1618 17 ( ( -LRB- cord-014597-66vd2mdu 1618 18 PCC PCC NNP cord-014597-66vd2mdu 1618 19 = = SYM cord-014597-66vd2mdu 1618 20 0.84 0.84 CD cord-014597-66vd2mdu 1618 21 and and CC cord-014597-66vd2mdu 1618 22 PCC PCC NNP cord-014597-66vd2mdu 1618 23 = = SYM cord-014597-66vd2mdu 1618 24 0.79 0.79 CD cord-014597-66vd2mdu 1618 25 , , , cord-014597-66vd2mdu 1618 26 respectively respectively RB cord-014597-66vd2mdu 1618 27 ) ) -RRB- cord-014597-66vd2mdu 1618 28 confirming confirm VBG cord-014597-66vd2mdu 1618 29 the the DT cord-014597-66vd2mdu 1618 30 data datum NNS cord-014597-66vd2mdu 1618 31 obtained obtain VBN cord-014597-66vd2mdu 1618 32 by by IN cord-014597-66vd2mdu 1618 33 western western JJ cord-014597-66vd2mdu 1618 34 blot blot NN cord-014597-66vd2mdu 1618 35 and and CC cord-014597-66vd2mdu 1618 36 qRT qRT NNP cord-014597-66vd2mdu 1618 37 - - HYPH cord-014597-66vd2mdu 1618 38 PCR PCR NNP cord-014597-66vd2mdu 1618 39 analysis analysis NN cord-014597-66vd2mdu 1618 40 . . . cord-014597-66vd2mdu 1619 1 A a DT cord-014597-66vd2mdu 1619 2 panel panel NN cord-014597-66vd2mdu 1619 3 of of IN cord-014597-66vd2mdu 1619 4 20 20 CD cord-014597-66vd2mdu 1619 5 cell cell NN cord-014597-66vd2mdu 1619 6 lines line NNS cord-014597-66vd2mdu 1619 7 has have VBZ cord-014597-66vd2mdu 1619 8 been be VBN cord-014597-66vd2mdu 1619 9 characterised characterise VBN cord-014597-66vd2mdu 1619 10 at at IN cord-014597-66vd2mdu 1619 11 the the DT cord-014597-66vd2mdu 1619 12 population population NN cord-014597-66vd2mdu 1619 13 level level NN cord-014597-66vd2mdu 1619 14 and and CC cord-014597-66vd2mdu 1619 15 show show VBP cord-014597-66vd2mdu 1619 16 a a DT cord-014597-66vd2mdu 1619 17 wide wide JJ cord-014597-66vd2mdu 1619 18 range range NN cord-014597-66vd2mdu 1619 19 of of IN cord-014597-66vd2mdu 1619 20 antibody antibody NN cord-014597-66vd2mdu 1619 21 expression expression NN cord-014597-66vd2mdu 1619 22 profiles profile NNS cord-014597-66vd2mdu 1619 23 at at IN cord-014597-66vd2mdu 1619 24 both both CC cord-014597-66vd2mdu 1619 25 the the DT cord-014597-66vd2mdu 1619 26 mRNA mrna NN cord-014597-66vd2mdu 1619 27 and and CC cord-014597-66vd2mdu 1619 28 protein protein NN cord-014597-66vd2mdu 1619 29 level level NN cord-014597-66vd2mdu 1619 30 . . . cord-014597-66vd2mdu 1620 1 In in IN cord-014597-66vd2mdu 1620 2 parallel parallel NN cord-014597-66vd2mdu 1620 3 , , , cord-014597-66vd2mdu 1620 4 assays assay NNS cord-014597-66vd2mdu 1620 5 have have VBP cord-014597-66vd2mdu 1620 6 been be VBN cord-014597-66vd2mdu 1620 7 developed develop VBN cord-014597-66vd2mdu 1620 8 for for IN cord-014597-66vd2mdu 1620 9 the the DT cord-014597-66vd2mdu 1620 10 ImageStream ImageStream NNP cord-014597-66vd2mdu 1620 11 to to TO cord-014597-66vd2mdu 1620 12 measure measure VB cord-014597-66vd2mdu 1620 13 HC HC NNP cord-014597-66vd2mdu 1620 14 and and CC cord-014597-66vd2mdu 1620 15 LC LC NNP cord-014597-66vd2mdu 1620 16 message message NN cord-014597-66vd2mdu 1620 17 and and CC cord-014597-66vd2mdu 1620 18 protein protein NN cord-014597-66vd2mdu 1620 19 amounts amount NNS cord-014597-66vd2mdu 1620 20 at at IN cord-014597-66vd2mdu 1620 21 the the DT cord-014597-66vd2mdu 1620 22 single single JJ cord-014597-66vd2mdu 1620 23 cell cell NN cord-014597-66vd2mdu 1620 24 level level NN cord-014597-66vd2mdu 1620 25 . . . cord-014597-66vd2mdu 1621 1 Protein protein NN cord-014597-66vd2mdu 1621 2 and and CC cord-014597-66vd2mdu 1621 3 message message NN cord-014597-66vd2mdu 1621 4 quantification quantification NN cord-014597-66vd2mdu 1621 5 with with IN cord-014597-66vd2mdu 1621 6 the the DT cord-014597-66vd2mdu 1621 7 ImageStream ImageStream NNP cord-014597-66vd2mdu 1621 8 are be VBP cord-014597-66vd2mdu 1621 9 consistent consistent JJ cord-014597-66vd2mdu 1621 10 with with IN cord-014597-66vd2mdu 1621 11 more more JJR cord-014597-66vd2mdu 1621 12 traditional traditional JJ cord-014597-66vd2mdu 1621 13 approaches approach NNS cord-014597-66vd2mdu 1621 14 , , , cord-014597-66vd2mdu 1621 15 such such JJ cord-014597-66vd2mdu 1621 16 as as IN cord-014597-66vd2mdu 1621 17 western western JJ cord-014597-66vd2mdu 1621 18 blots blot NNS cord-014597-66vd2mdu 1621 19 and and CC cord-014597-66vd2mdu 1621 20 qRT qRT NNP cord-014597-66vd2mdu 1621 21 - - HYPH cord-014597-66vd2mdu 1621 22 PCR PCR NNP cord-014597-66vd2mdu 1621 23 , , , cord-014597-66vd2mdu 1621 24 that that WDT cord-014597-66vd2mdu 1621 25 operate operate VBP cord-014597-66vd2mdu 1621 26 at at IN cord-014597-66vd2mdu 1621 27 the the DT cord-014597-66vd2mdu 1621 28 population population NN cord-014597-66vd2mdu 1621 29 level level NN cord-014597-66vd2mdu 1621 30 . . . cord-014597-66vd2mdu 1622 1 The the DT cord-014597-66vd2mdu 1622 2 developed develop VBN cord-014597-66vd2mdu 1622 3 assays assay NNS cord-014597-66vd2mdu 1622 4 are be VBP cord-014597-66vd2mdu 1622 5 now now RB cord-014597-66vd2mdu 1622 6 being be VBG cord-014597-66vd2mdu 1622 7 used use VBN cord-014597-66vd2mdu 1622 8 to to TO cord-014597-66vd2mdu 1622 9 investigate investigate VB cord-014597-66vd2mdu 1622 10 single single JJ cord-014597-66vd2mdu 1622 11 cell cell NN cord-014597-66vd2mdu 1622 12 productivity productivity NN cord-014597-66vd2mdu 1622 13 attributes attribute NNS cord-014597-66vd2mdu 1622 14 and and CC cord-014597-66vd2mdu 1622 15 for for IN cord-014597-66vd2mdu 1622 16 the the DT cord-014597-66vd2mdu 1622 17 isolation isolation NN cord-014597-66vd2mdu 1622 18 of of IN cord-014597-66vd2mdu 1622 19 more more JJR cord-014597-66vd2mdu 1622 20 productive productive JJ cord-014597-66vd2mdu 1622 21 clones clone NNS cord-014597-66vd2mdu 1622 22 . . . cord-014597-66vd2mdu 1623 1 Background Background NNP cord-014597-66vd2mdu 1623 2 Productivity Productivity NNP cord-014597-66vd2mdu 1623 3 and and CC cord-014597-66vd2mdu 1623 4 stability stability NN cord-014597-66vd2mdu 1623 5 are be VBP cord-014597-66vd2mdu 1623 6 key key JJ cord-014597-66vd2mdu 1623 7 factors factor NNS cord-014597-66vd2mdu 1623 8 for for IN cord-014597-66vd2mdu 1623 9 the the DT cord-014597-66vd2mdu 1623 10 selection selection NN cord-014597-66vd2mdu 1623 11 of of IN cord-014597-66vd2mdu 1623 12 cell cell NN cord-014597-66vd2mdu 1623 13 line line NN cord-014597-66vd2mdu 1623 14 in in IN cord-014597-66vd2mdu 1623 15 protein protein NN cord-014597-66vd2mdu 1623 16 drugs drug NNS cord-014597-66vd2mdu 1623 17 production production NN cord-014597-66vd2mdu 1623 18 . . . cord-014597-66vd2mdu 1624 1 Large large JJ cord-014597-66vd2mdu 1624 2 amount amount NN cord-014597-66vd2mdu 1624 3 of of IN cord-014597-66vd2mdu 1624 4 target target NN cord-014597-66vd2mdu 1624 5 gene gene NN cord-014597-66vd2mdu 1624 6 integrated integrate VBN cord-014597-66vd2mdu 1624 7 in in IN cord-014597-66vd2mdu 1624 8 cell cell NN cord-014597-66vd2mdu 1624 9 genome genome NN cord-014597-66vd2mdu 1624 10 could could MD cord-014597-66vd2mdu 1624 11 lead lead VB cord-014597-66vd2mdu 1624 12 to to IN cord-014597-66vd2mdu 1624 13 the the DT cord-014597-66vd2mdu 1624 14 instability instability NN cord-014597-66vd2mdu 1624 15 of of IN cord-014597-66vd2mdu 1624 16 production production NN cord-014597-66vd2mdu 1624 17 . . . cord-014597-66vd2mdu 1625 1 Therefore therefore RB cord-014597-66vd2mdu 1625 2 , , , cord-014597-66vd2mdu 1625 3 cells cell NNS cord-014597-66vd2mdu 1625 4 with with IN cord-014597-66vd2mdu 1625 5 low low JJ cord-014597-66vd2mdu 1625 6 copies copy NNS cord-014597-66vd2mdu 1625 7 of of IN cord-014597-66vd2mdu 1625 8 target target NN cord-014597-66vd2mdu 1625 9 gene gene NN cord-014597-66vd2mdu 1625 10 integrated integrate VBN cord-014597-66vd2mdu 1625 11 in in IN cord-014597-66vd2mdu 1625 12 high high JJ cord-014597-66vd2mdu 1625 13 yield yield NN cord-014597-66vd2mdu 1625 14 sites site NNS cord-014597-66vd2mdu 1625 15 could could MD cord-014597-66vd2mdu 1625 16 be be VB cord-014597-66vd2mdu 1625 17 an an DT cord-014597-66vd2mdu 1625 18 ideal ideal JJ cord-014597-66vd2mdu 1625 19 production production NN cord-014597-66vd2mdu 1625 20 cells cell NNS cord-014597-66vd2mdu 1625 21 for for IN cord-014597-66vd2mdu 1625 22 manufacturing manufacturing NN cord-014597-66vd2mdu 1625 23 . . . cord-014597-66vd2mdu 1626 1 It -PRON- PRP cord-014597-66vd2mdu 1626 2 has have VBZ cord-014597-66vd2mdu 1626 3 been be VBN cord-014597-66vd2mdu 1626 4 known know VBN cord-014597-66vd2mdu 1626 5 that that IN cord-014597-66vd2mdu 1626 6 the the DT cord-014597-66vd2mdu 1626 7 transposon transposon NN cord-014597-66vd2mdu 1626 8 system system NN cord-014597-66vd2mdu 1626 9 can can MD cord-014597-66vd2mdu 1626 10 control control VB cord-014597-66vd2mdu 1626 11 the the DT cord-014597-66vd2mdu 1626 12 integrated integrate VBN cord-014597-66vd2mdu 1626 13 copy copy NN cord-014597-66vd2mdu 1626 14 number number NN cord-014597-66vd2mdu 1626 15 of of IN cord-014597-66vd2mdu 1626 16 target target NN cord-014597-66vd2mdu 1626 17 gene gene NN cord-014597-66vd2mdu 1626 18 and and CC cord-014597-66vd2mdu 1626 19 can can MD cord-014597-66vd2mdu 1626 20 generate generate VB cord-014597-66vd2mdu 1626 21 high high JJ cord-014597-66vd2mdu 1626 22 yield yield NN cord-014597-66vd2mdu 1626 23 producing produce VBG cord-014597-66vd2mdu 1626 24 cells cell NNS cord-014597-66vd2mdu 1626 25 , , , cord-014597-66vd2mdu 1626 26 it -PRON- PRP cord-014597-66vd2mdu 1626 27 could could MD cord-014597-66vd2mdu 1626 28 be be VB cord-014597-66vd2mdu 1626 29 a a DT cord-014597-66vd2mdu 1626 30 great great JJ cord-014597-66vd2mdu 1626 31 approach approach NN cord-014597-66vd2mdu 1626 32 to to TO cord-014597-66vd2mdu 1626 33 generate generate VB cord-014597-66vd2mdu 1626 34 stable stable JJ cord-014597-66vd2mdu 1626 35 high high JJ cord-014597-66vd2mdu 1626 36 yield yield NN cord-014597-66vd2mdu 1626 37 producing produce VBG cord-014597-66vd2mdu 1626 38 cell cell NN cord-014597-66vd2mdu 1626 39 lines line NNS cord-014597-66vd2mdu 1626 40 carrying carry VBG cord-014597-66vd2mdu 1626 41 low low JJ cord-014597-66vd2mdu 1626 42 copies copy NNS cord-014597-66vd2mdu 1626 43 of of IN cord-014597-66vd2mdu 1626 44 target target NN cord-014597-66vd2mdu 1626 45 gene gene NN cord-014597-66vd2mdu 1626 46 through through IN cord-014597-66vd2mdu 1626 47 transposon transposon NN cord-014597-66vd2mdu 1626 48 system system NN cord-014597-66vd2mdu 1626 49 . . . cord-014597-66vd2mdu 1627 1 We -PRON- PRP cord-014597-66vd2mdu 1627 2 intended intend VBD cord-014597-66vd2mdu 1627 3 to to TO cord-014597-66vd2mdu 1627 4 develop develop VB cord-014597-66vd2mdu 1627 5 a a DT cord-014597-66vd2mdu 1627 6 platform platform NN cord-014597-66vd2mdu 1627 7 to to TO cord-014597-66vd2mdu 1627 8 generate generate VB cord-014597-66vd2mdu 1627 9 high high JJ cord-014597-66vd2mdu 1627 10 yield yield NN cord-014597-66vd2mdu 1627 11 producing produce VBG cord-014597-66vd2mdu 1627 12 cell cell NN cord-014597-66vd2mdu 1627 13 lines line NNS cord-014597-66vd2mdu 1627 14 carrying carry VBG cord-014597-66vd2mdu 1627 15 1 1 CD cord-014597-66vd2mdu 1627 16 - - SYM cord-014597-66vd2mdu 1627 17 2 2 CD cord-014597-66vd2mdu 1627 18 copy copy NN cord-014597-66vd2mdu 1627 19 of of IN cord-014597-66vd2mdu 1627 20 the the DT cord-014597-66vd2mdu 1627 21 integrated integrated JJ cord-014597-66vd2mdu 1627 22 target target NN cord-014597-66vd2mdu 1627 23 gene gene NN cord-014597-66vd2mdu 1627 24 using use VBG cord-014597-66vd2mdu 1627 25 transposon transposon NN cord-014597-66vd2mdu 1627 26 system system NN cord-014597-66vd2mdu 1627 27 . . . cord-014597-66vd2mdu 1628 1 Two two CD cord-014597-66vd2mdu 1628 2 CHO CHO NNP cord-014597-66vd2mdu 1628 3 cell cell NN cord-014597-66vd2mdu 1628 4 lines line NNS cord-014597-66vd2mdu 1628 5 , , , cord-014597-66vd2mdu 1628 6 CHO CHO NNP cord-014597-66vd2mdu 1628 7 - - HYPH cord-014597-66vd2mdu 1628 8 S S NNP cord-014597-66vd2mdu 1628 9 cells cell NNS cord-014597-66vd2mdu 1628 10 and and CC cord-014597-66vd2mdu 1628 11 DXB11 DXB11 NNP cord-014597-66vd2mdu 1628 12 cells cell NNS cord-014597-66vd2mdu 1628 13 , , , cord-014597-66vd2mdu 1628 14 have have VBP cord-014597-66vd2mdu 1628 15 been be VBN cord-014597-66vd2mdu 1628 16 applied apply VBN cord-014597-66vd2mdu 1628 17 . . . cord-014597-66vd2mdu 1629 1 Cells cell NNS cord-014597-66vd2mdu 1629 2 were be VBD cord-014597-66vd2mdu 1629 3 co co VBN cord-014597-66vd2mdu 1629 4 - - VBN cord-014597-66vd2mdu 1629 5 transfected transfecte VBN cord-014597-66vd2mdu 1629 6 with with IN cord-014597-66vd2mdu 1629 7 transposon transposon NN cord-014597-66vd2mdu 1629 8 and and CC cord-014597-66vd2mdu 1629 9 target target NN cord-014597-66vd2mdu 1629 10 gene gene NN cord-014597-66vd2mdu 1629 11 expression expression NN cord-014597-66vd2mdu 1629 12 plasmids plasmid NNS cord-014597-66vd2mdu 1629 13 . . . cord-014597-66vd2mdu 1630 1 After after IN cord-014597-66vd2mdu 1630 2 drug drug NN cord-014597-66vd2mdu 1630 3 selection selection NN cord-014597-66vd2mdu 1630 4 , , , cord-014597-66vd2mdu 1630 5 the the DT cord-014597-66vd2mdu 1630 6 cell cell NN cord-014597-66vd2mdu 1630 7 pool pool NN cord-014597-66vd2mdu 1630 8 with with IN cord-014597-66vd2mdu 1630 9 highest high JJS cord-014597-66vd2mdu 1630 10 productivity productivity NN cord-014597-66vd2mdu 1630 11 per per IN cord-014597-66vd2mdu 1630 12 target target NN cord-014597-66vd2mdu 1630 13 gene gene NN cord-014597-66vd2mdu 1630 14 copy copy NN cord-014597-66vd2mdu 1630 15 was be VBD cord-014597-66vd2mdu 1630 16 applied apply VBN cord-014597-66vd2mdu 1630 17 to to IN cord-014597-66vd2mdu 1630 18 single single JJ cord-014597-66vd2mdu 1630 19 cell cell NN cord-014597-66vd2mdu 1630 20 cloning cloning NN cord-014597-66vd2mdu 1630 21 . . . cord-014597-66vd2mdu 1631 1 The the DT cord-014597-66vd2mdu 1631 2 productivity productivity NN cord-014597-66vd2mdu 1631 3 and and CC cord-014597-66vd2mdu 1631 4 copy copy NN cord-014597-66vd2mdu 1631 5 number number NN cord-014597-66vd2mdu 1631 6 of of IN cord-014597-66vd2mdu 1631 7 cell cell NN cord-014597-66vd2mdu 1631 8 clones clone NNS cord-014597-66vd2mdu 1631 9 were be VBD cord-014597-66vd2mdu 1631 10 determined determine VBN cord-014597-66vd2mdu 1631 11 , , , cord-014597-66vd2mdu 1631 12 and and CC cord-014597-66vd2mdu 1631 13 the the DT cord-014597-66vd2mdu 1631 14 stability stability NN cord-014597-66vd2mdu 1631 15 of of IN cord-014597-66vd2mdu 1631 16 cell cell NN cord-014597-66vd2mdu 1631 17 clones clone NNS cord-014597-66vd2mdu 1631 18 was be VBD cord-014597-66vd2mdu 1631 19 analysed analyse VBN cord-014597-66vd2mdu 1631 20 after after IN cord-014597-66vd2mdu 1631 21 culture culture NN cord-014597-66vd2mdu 1631 22 of of IN cord-014597-66vd2mdu 1631 23 about about RB cord-014597-66vd2mdu 1631 24 60 60 CD cord-014597-66vd2mdu 1631 25 generations generation NNS cord-014597-66vd2mdu 1631 26 . . . cord-014597-66vd2mdu 1632 1 In in IN cord-014597-66vd2mdu 1632 2 the the DT cord-014597-66vd2mdu 1632 3 stable stable JJ cord-014597-66vd2mdu 1632 4 pools pool NNS cord-014597-66vd2mdu 1632 5 of of IN cord-014597-66vd2mdu 1632 6 CHO CHO NNP cord-014597-66vd2mdu 1632 7 - - HYPH cord-014597-66vd2mdu 1632 8 S S NNP cord-014597-66vd2mdu 1632 9 and and CC cord-014597-66vd2mdu 1632 10 DXB11 DXB11 NNP cord-014597-66vd2mdu 1632 11 cells cell NNS cord-014597-66vd2mdu 1632 12 , , , cord-014597-66vd2mdu 1632 13 the the DT cord-014597-66vd2mdu 1632 14 productivities productivity NNS cord-014597-66vd2mdu 1632 15 per per IN cord-014597-66vd2mdu 1632 16 integrated integrate VBN cord-014597-66vd2mdu 1632 17 target target NN cord-014597-66vd2mdu 1632 18 gene gene NN cord-014597-66vd2mdu 1632 19 copy copy NN cord-014597-66vd2mdu 1632 20 were be VBD cord-014597-66vd2mdu 1632 21 about about RB cord-014597-66vd2mdu 1632 22 11 11 CD cord-014597-66vd2mdu 1632 23 - - SYM cord-014597-66vd2mdu 1632 24 13 13 CD cord-014597-66vd2mdu 1632 25 mg mg NNP cord-014597-66vd2mdu 1632 26 / / SYM cord-014597-66vd2mdu 1632 27 L L NNP cord-014597-66vd2mdu 1632 28 / / SYM cord-014597-66vd2mdu 1632 29 copy copy NN cord-014597-66vd2mdu 1632 30 and and CC cord-014597-66vd2mdu 1632 31 68 68 CD cord-014597-66vd2mdu 1632 32 - - SYM cord-014597-66vd2mdu 1632 33 75 75 CD cord-014597-66vd2mdu 1632 34 mg mg NNP cord-014597-66vd2mdu 1632 35 / / SYM cord-014597-66vd2mdu 1632 36 L L NNP cord-014597-66vd2mdu 1632 37 / / SYM cord-014597-66vd2mdu 1632 38 copy copy VBP cord-014597-66vd2mdu 1632 39 in in IN cord-014597-66vd2mdu 1632 40 a a DT cord-014597-66vd2mdu 1632 41 batch batch NN cord-014597-66vd2mdu 1632 42 culture culture NN cord-014597-66vd2mdu 1632 43 , , , cord-014597-66vd2mdu 1632 44 respectively respectively RB cord-014597-66vd2mdu 1632 45 . . . cord-014597-66vd2mdu 1633 1 After after IN cord-014597-66vd2mdu 1633 2 single single JJ cord-014597-66vd2mdu 1633 3 cell cell NN cord-014597-66vd2mdu 1633 4 cloning cloning NN cord-014597-66vd2mdu 1633 5 , , , cord-014597-66vd2mdu 1633 6 the the DT cord-014597-66vd2mdu 1633 7 integrated integrated JJ cord-014597-66vd2mdu 1633 8 copy copy NN cord-014597-66vd2mdu 1633 9 numbers number NNS cord-014597-66vd2mdu 1633 10 in in IN cord-014597-66vd2mdu 1633 11 most most JJS cord-014597-66vd2mdu 1633 12 cell cell NN cord-014597-66vd2mdu 1633 13 clones clone NNS cord-014597-66vd2mdu 1633 14 were be VBD cord-014597-66vd2mdu 1633 15 less less JJR cord-014597-66vd2mdu 1633 16 than than IN cord-014597-66vd2mdu 1633 17 three three CD cord-014597-66vd2mdu 1633 18 copies copy NNS cord-014597-66vd2mdu 1633 19 per per IN cord-014597-66vd2mdu 1633 20 cell cell NN cord-014597-66vd2mdu 1633 21 . . . cord-014597-66vd2mdu 1634 1 In in IN cord-014597-66vd2mdu 1634 2 CHO CHO NNP cord-014597-66vd2mdu 1634 3 - - HYPH cord-014597-66vd2mdu 1634 4 S S NNP cord-014597-66vd2mdu 1634 5 and and CC cord-014597-66vd2mdu 1634 6 DXB11 DXB11 NNP cord-014597-66vd2mdu 1634 7 cell cell NN cord-014597-66vd2mdu 1634 8 clones clone NNS cord-014597-66vd2mdu 1634 9 , , , cord-014597-66vd2mdu 1634 10 the the DT cord-014597-66vd2mdu 1634 11 productivities productivity NNS cord-014597-66vd2mdu 1634 12 per per IN cord-014597-66vd2mdu 1634 13 integrated integrate VBN cord-014597-66vd2mdu 1634 14 target target NN cord-014597-66vd2mdu 1634 15 gene gene NN cord-014597-66vd2mdu 1634 16 copy copy NN cord-014597-66vd2mdu 1634 17 were be VBD cord-014597-66vd2mdu 1634 18 20 20 CD cord-014597-66vd2mdu 1634 19 - - SYM cord-014597-66vd2mdu 1634 20 60 60 CD cord-014597-66vd2mdu 1634 21 mg mg NNP cord-014597-66vd2mdu 1634 22 / / SYM cord-014597-66vd2mdu 1634 23 L L NNP cord-014597-66vd2mdu 1634 24 / / SYM cord-014597-66vd2mdu 1634 25 copy copy NN cord-014597-66vd2mdu 1634 26 and and CC cord-014597-66vd2mdu 1634 27 60 60 CD cord-014597-66vd2mdu 1634 28 - - SYM cord-014597-66vd2mdu 1634 29 150 150 CD cord-014597-66vd2mdu 1634 30 mg mg NNP cord-014597-66vd2mdu 1634 31 / / SYM cord-014597-66vd2mdu 1634 32 L L NNP cord-014597-66vd2mdu 1634 33 / / SYM cord-014597-66vd2mdu 1634 34 copy copy VBP cord-014597-66vd2mdu 1634 35 in in IN cord-014597-66vd2mdu 1634 36 a a DT cord-014597-66vd2mdu 1634 37 batch batch NN cord-014597-66vd2mdu 1634 38 culture culture NN cord-014597-66vd2mdu 1634 39 , , , cord-014597-66vd2mdu 1634 40 respectively respectively RB cord-014597-66vd2mdu 1634 41 . . . cord-014597-66vd2mdu 1635 1 The the DT cord-014597-66vd2mdu 1635 2 productivity productivity NN cord-014597-66vd2mdu 1635 3 per per IN cord-014597-66vd2mdu 1635 4 integrated integrate VBN cord-014597-66vd2mdu 1635 5 target target NN cord-014597-66vd2mdu 1635 6 gene gene NN cord-014597-66vd2mdu 1635 7 in in IN cord-014597-66vd2mdu 1635 8 cell cell NN cord-014597-66vd2mdu 1635 9 clones clone NNS cord-014597-66vd2mdu 1635 10 developed develop VBN cord-014597-66vd2mdu 1635 11 by by IN cord-014597-66vd2mdu 1635 12 the the DT cord-014597-66vd2mdu 1635 13 transposon transposon NN cord-014597-66vd2mdu 1635 14 system system NN cord-014597-66vd2mdu 1635 15 was be VBD cord-014597-66vd2mdu 1635 16 much much RB cord-014597-66vd2mdu 1635 17 higher high JJR cord-014597-66vd2mdu 1635 18 than than IN cord-014597-66vd2mdu 1635 19 that that DT cord-014597-66vd2mdu 1635 20 in in IN cord-014597-66vd2mdu 1635 21 cell cell NN cord-014597-66vd2mdu 1635 22 clones clone NNS cord-014597-66vd2mdu 1635 23 developed develop VBN cord-014597-66vd2mdu 1635 24 by by IN cord-014597-66vd2mdu 1635 25 random random JJ cord-014597-66vd2mdu 1635 26 integration integration NN cord-014597-66vd2mdu 1635 27 ( ( -LRB- cord-014597-66vd2mdu 1635 28 Fig Fig NNP cord-014597-66vd2mdu 1635 29 . . . cord-014597-66vd2mdu 1635 30 1a 1a CD cord-014597-66vd2mdu 1635 31 and and CC cord-014597-66vd2mdu 1635 32 b b LS cord-014597-66vd2mdu 1635 33 ) ) -RRB- cord-014597-66vd2mdu 1635 34 . . . cord-014597-66vd2mdu 1636 1 To to TO cord-014597-66vd2mdu 1636 2 evaluate evaluate VB cord-014597-66vd2mdu 1636 3 the the DT cord-014597-66vd2mdu 1636 4 productivity productivity NN cord-014597-66vd2mdu 1636 5 stability stability NN cord-014597-66vd2mdu 1636 6 of of IN cord-014597-66vd2mdu 1636 7 cell cell NN cord-014597-66vd2mdu 1636 8 clones clone NNS cord-014597-66vd2mdu 1636 9 developed develop VBN cord-014597-66vd2mdu 1636 10 by by IN cord-014597-66vd2mdu 1636 11 the the DT cord-014597-66vd2mdu 1636 12 transposon transposon NN cord-014597-66vd2mdu 1636 13 system system NN cord-014597-66vd2mdu 1636 14 , , , cord-014597-66vd2mdu 1636 15 ten ten CD cord-014597-66vd2mdu 1636 16 cell cell NN cord-014597-66vd2mdu 1636 17 clones clone NNS cord-014597-66vd2mdu 1636 18 at at IN cord-014597-66vd2mdu 1636 19 generation generation NN cord-014597-66vd2mdu 1636 20 0 0 CD cord-014597-66vd2mdu 1636 21 , , , cord-014597-66vd2mdu 1636 22 30 30 CD cord-014597-66vd2mdu 1636 23 , , , cord-014597-66vd2mdu 1636 24 60 60 CD cord-014597-66vd2mdu 1636 25 , , , cord-014597-66vd2mdu 1636 26 and and CC cord-014597-66vd2mdu 1636 27 100 100 CD cord-014597-66vd2mdu 1636 28 were be VBD cord-014597-66vd2mdu 1636 29 applied apply VBN cord-014597-66vd2mdu 1636 30 in in IN cord-014597-66vd2mdu 1636 31 the the DT cord-014597-66vd2mdu 1636 32 analysis analysis NN cord-014597-66vd2mdu 1636 33 . . . cord-014597-66vd2mdu 1637 1 Of of IN cord-014597-66vd2mdu 1637 2 interest interest NN cord-014597-66vd2mdu 1637 3 , , , cord-014597-66vd2mdu 1637 4 about about RB cord-014597-66vd2mdu 1637 5 80 80 CD cord-014597-66vd2mdu 1637 6 % % NN cord-014597-66vd2mdu 1637 7 of of IN cord-014597-66vd2mdu 1637 8 cell cell NN cord-014597-66vd2mdu 1637 9 clones clone NNS cord-014597-66vd2mdu 1637 10 were be VBD cord-014597-66vd2mdu 1637 11 stable stable JJ cord-014597-66vd2mdu 1637 12 at at IN cord-014597-66vd2mdu 1637 13 generation generation NN cord-014597-66vd2mdu 1637 14 60 60 CD cord-014597-66vd2mdu 1637 15 , , , cord-014597-66vd2mdu 1637 16 but but CC cord-014597-66vd2mdu 1637 17 lost lose VBD cord-014597-66vd2mdu 1637 18 the the DT cord-014597-66vd2mdu 1637 19 productivity productivity NN cord-014597-66vd2mdu 1637 20 at at IN cord-014597-66vd2mdu 1637 21 generation generation NN cord-014597-66vd2mdu 1637 22 100 100 CD cord-014597-66vd2mdu 1638 1 ( ( -LRB- cord-014597-66vd2mdu 1638 2 Fig Fig NNP cord-014597-66vd2mdu 1638 3 . . . cord-014597-66vd2mdu 1638 4 1c 1c NNP cord-014597-66vd2mdu 1638 5 ) ) -RRB- cord-014597-66vd2mdu 1638 6 , , , cord-014597-66vd2mdu 1638 7 implying imply VBG cord-014597-66vd2mdu 1638 8 the the DT cord-014597-66vd2mdu 1638 9 most most JJS cord-014597-66vd2mdu 1638 10 cell cell NN cord-014597-66vd2mdu 1638 11 clones clone NNS cord-014597-66vd2mdu 1638 12 could could MD cord-014597-66vd2mdu 1638 13 maintain maintain VB cord-014597-66vd2mdu 1638 14 the the DT cord-014597-66vd2mdu 1638 15 stability stability NN cord-014597-66vd2mdu 1638 16 within within IN cord-014597-66vd2mdu 1638 17 2 2 CD cord-014597-66vd2mdu 1638 18 months month NNS cord-014597-66vd2mdu 1638 19 . . . cord-014597-66vd2mdu 1639 1 Using use VBG cord-014597-66vd2mdu 1639 2 the the DT cord-014597-66vd2mdu 1639 3 optimized optimize VBN cord-014597-66vd2mdu 1639 4 conditions condition NNS cord-014597-66vd2mdu 1639 5 of of IN cord-014597-66vd2mdu 1639 6 the the DT cord-014597-66vd2mdu 1639 7 transposon transposon NN cord-014597-66vd2mdu 1639 8 system system NN cord-014597-66vd2mdu 1639 9 to to TO cord-014597-66vd2mdu 1639 10 develop develop VB cord-014597-66vd2mdu 1639 11 the the DT cord-014597-66vd2mdu 1639 12 stable stable JJ cord-014597-66vd2mdu 1639 13 gene gene NN cord-014597-66vd2mdu 1639 14 expression expression NN cord-014597-66vd2mdu 1639 15 cells cell NNS cord-014597-66vd2mdu 1639 16 , , , cord-014597-66vd2mdu 1639 17 the the DT cord-014597-66vd2mdu 1639 18 productivity productivity NN cord-014597-66vd2mdu 1639 19 per per IN cord-014597-66vd2mdu 1639 20 integrated integrate VBN cord-014597-66vd2mdu 1639 21 target target NN cord-014597-66vd2mdu 1639 22 gene gene NN cord-014597-66vd2mdu 1639 23 was be VBD cord-014597-66vd2mdu 1639 24 higher high JJR cord-014597-66vd2mdu 1639 25 than than IN cord-014597-66vd2mdu 1639 26 random random JJ cord-014597-66vd2mdu 1639 27 integration integration NN cord-014597-66vd2mdu 1639 28 . . . cord-014597-66vd2mdu 1640 1 These these DT cord-014597-66vd2mdu 1640 2 results result NNS cord-014597-66vd2mdu 1640 3 suggested suggest VBD cord-014597-66vd2mdu 1640 4 that that IN cord-014597-66vd2mdu 1640 5 our -PRON- PRP$ cord-014597-66vd2mdu 1640 6 platform platform NN cord-014597-66vd2mdu 1640 7 is be VBZ cord-014597-66vd2mdu 1640 8 capable capable JJ cord-014597-66vd2mdu 1640 9 to to TO cord-014597-66vd2mdu 1640 10 develop develop VB cord-014597-66vd2mdu 1640 11 high high JJ cord-014597-66vd2mdu 1640 12 yield yield NN cord-014597-66vd2mdu 1640 13 producing produce VBG cord-014597-66vd2mdu 1640 14 cells cell NNS cord-014597-66vd2mdu 1640 15 with with IN cord-014597-66vd2mdu 1640 16 1 1 CD cord-014597-66vd2mdu 1640 17 - - SYM cord-014597-66vd2mdu 1640 18 2 2 CD cord-014597-66vd2mdu 1640 19 copy copy NN cord-014597-66vd2mdu 1640 20 of of IN cord-014597-66vd2mdu 1640 21 integrated integrated JJ cord-014597-66vd2mdu 1640 22 target target NN cord-014597-66vd2mdu 1640 23 antibody antibody NN cord-014597-66vd2mdu 1640 24 gene gene NN cord-014597-66vd2mdu 1640 25 and and CC cord-014597-66vd2mdu 1640 26 can can MD cord-014597-66vd2mdu 1640 27 be be VB cord-014597-66vd2mdu 1640 28 applied apply VBN cord-014597-66vd2mdu 1640 29 to to TO cord-014597-66vd2mdu 1640 30 identify identify VB cord-014597-66vd2mdu 1640 31 high high JJ cord-014597-66vd2mdu 1640 32 yield yield NN cord-014597-66vd2mdu 1640 33 integration integration NN cord-014597-66vd2mdu 1640 34 sites site NNS cord-014597-66vd2mdu 1640 35 . . . cord-014597-66vd2mdu 1641 1 Background Background NNP cord-014597-66vd2mdu 1641 2 Mammalian mammalian JJ cord-014597-66vd2mdu 1641 3 cells cell NNS cord-014597-66vd2mdu 1641 4 show show VBP cord-014597-66vd2mdu 1641 5 an an DT cord-014597-66vd2mdu 1641 6 inefficient inefficient JJ cord-014597-66vd2mdu 1641 7 metabolism metabolism NN cord-014597-66vd2mdu 1641 8 characterized characterize VBN cord-014597-66vd2mdu 1641 9 by by IN cord-014597-66vd2mdu 1641 10 high high JJ cord-014597-66vd2mdu 1641 11 glucose glucose NN cord-014597-66vd2mdu 1641 12 uptake uptake NN cord-014597-66vd2mdu 1641 13 and and CC cord-014597-66vd2mdu 1641 14 the the DT cord-014597-66vd2mdu 1641 15 production production NN cord-014597-66vd2mdu 1641 16 of of IN cord-014597-66vd2mdu 1641 17 high high JJ cord-014597-66vd2mdu 1641 18 amounts amount NNS cord-014597-66vd2mdu 1641 19 of of IN cord-014597-66vd2mdu 1641 20 lactate lactate NN cord-014597-66vd2mdu 1641 21 , , , cord-014597-66vd2mdu 1641 22 a a DT cord-014597-66vd2mdu 1641 23 widely widely RB cord-014597-66vd2mdu 1641 24 known know VBN cord-014597-66vd2mdu 1641 25 growth growth NN cord-014597-66vd2mdu 1641 26 inhibition inhibition NN cord-014597-66vd2mdu 1641 27 by by IN cord-014597-66vd2mdu 1641 28 - - HYPH cord-014597-66vd2mdu 1641 29 product product NN cord-014597-66vd2mdu 1641 30 [ [ -LRB- cord-014597-66vd2mdu 1641 31 1 1 CD cord-014597-66vd2mdu 1641 32 ] ] -RRB- cord-014597-66vd2mdu 1641 33 . . . cord-014597-66vd2mdu 1642 1 Recently recently RB cord-014597-66vd2mdu 1642 2 , , , cord-014597-66vd2mdu 1642 3 we -PRON- PRP cord-014597-66vd2mdu 1642 4 have have VBP cord-014597-66vd2mdu 1642 5 observed observe VBN cord-014597-66vd2mdu 1642 6 a a DT cord-014597-66vd2mdu 1642 7 different different JJ cord-014597-66vd2mdu 1642 8 glucose glucose NN cord-014597-66vd2mdu 1642 9 - - HYPH cord-014597-66vd2mdu 1642 10 lactate lactate NN cord-014597-66vd2mdu 1642 11 metabolism metabolism NN cord-014597-66vd2mdu 1642 12 in in IN cord-014597-66vd2mdu 1642 13 some some DT cord-014597-66vd2mdu 1642 14 cell cell NN cord-014597-66vd2mdu 1642 15 lines line NNS cord-014597-66vd2mdu 1642 16 . . . cord-014597-66vd2mdu 1643 1 While while IN cord-014597-66vd2mdu 1643 2 some some DT cord-014597-66vd2mdu 1643 3 cell cell NN cord-014597-66vd2mdu 1643 4 lines line NNS cord-014597-66vd2mdu 1643 5 are be VBP cord-014597-66vd2mdu 1643 6 unable unable JJ cord-014597-66vd2mdu 1643 7 to to TO cord-014597-66vd2mdu 1643 8 metabolize metabolize VB cord-014597-66vd2mdu 1643 9 lactate lactate NN cord-014597-66vd2mdu 1643 10 , , , cord-014597-66vd2mdu 1643 11 others other NNS cord-014597-66vd2mdu 1643 12 can can MD cord-014597-66vd2mdu 1643 13 co co VB cord-014597-66vd2mdu 1643 14 - - VB cord-014597-66vd2mdu 1643 15 metabolize metabolize VB cord-014597-66vd2mdu 1643 16 simultaneously simultaneously RB cord-014597-66vd2mdu 1643 17 glucose glucose NN cord-014597-66vd2mdu 1643 18 and and CC cord-014597-66vd2mdu 1643 19 lactate lactate NN cord-014597-66vd2mdu 1643 20 under under IN cord-014597-66vd2mdu 1643 21 certain certain JJ cord-014597-66vd2mdu 1643 22 culture culture NN cord-014597-66vd2mdu 1643 23 conditions condition NNS cord-014597-66vd2mdu 1643 24 , , , cord-014597-66vd2mdu 1643 25 even even RB cord-014597-66vd2mdu 1643 26 during during IN cord-014597-66vd2mdu 1643 27 the the DT cord-014597-66vd2mdu 1643 28 exponential exponential JJ cord-014597-66vd2mdu 1643 29 growth growth NN cord-014597-66vd2mdu 1643 30 phase phase NN cord-014597-66vd2mdu 1643 31 [ [ -LRB- cord-014597-66vd2mdu 1643 32 2 2 CD cord-014597-66vd2mdu 1643 33 ] ] -RRB- cord-014597-66vd2mdu 1643 34 . . . cord-014597-66vd2mdu 1644 1 These these DT cord-014597-66vd2mdu 1644 2 metabolic metabolic JJ cord-014597-66vd2mdu 1644 3 differences difference NNS cord-014597-66vd2mdu 1644 4 between between IN cord-014597-66vd2mdu 1644 5 different different JJ cord-014597-66vd2mdu 1644 6 mammalian mammalian JJ cord-014597-66vd2mdu 1644 7 cell cell NN cord-014597-66vd2mdu 1644 8 lines line NNS cord-014597-66vd2mdu 1644 9 ( ( -LRB- cord-014597-66vd2mdu 1644 10 CHO CHO NNP cord-014597-66vd2mdu 1644 11 , , , cord-014597-66vd2mdu 1644 12 HEK293 HEK293 NNP cord-014597-66vd2mdu 1644 13 and and CC cord-014597-66vd2mdu 1644 14 hybridoma hybridoma NN cord-014597-66vd2mdu 1644 15 ) ) -RRB- cord-014597-66vd2mdu 1644 16 have have VBP cord-014597-66vd2mdu 1644 17 been be VBN cord-014597-66vd2mdu 1644 18 studied study VBN cord-014597-66vd2mdu 1644 19 by by IN cord-014597-66vd2mdu 1644 20 means mean NNS cord-014597-66vd2mdu 1644 21 of of IN cord-014597-66vd2mdu 1644 22 Flux Flux NNP cord-014597-66vd2mdu 1644 23 Balance Balance NNP cord-014597-66vd2mdu 1644 24 Analysis Analysis NNP cord-014597-66vd2mdu 1644 25 ( ( -LRB- cord-014597-66vd2mdu 1644 26 FBA FBA NNP cord-014597-66vd2mdu 1644 27 ) ) -RRB- cord-014597-66vd2mdu 1644 28 . . . cord-014597-66vd2mdu 1645 1 Three three CD cord-014597-66vd2mdu 1645 2 different different JJ cord-014597-66vd2mdu 1645 3 cell cell NN cord-014597-66vd2mdu 1645 4 lines line NNS cord-014597-66vd2mdu 1645 5 were be VBD cord-014597-66vd2mdu 1645 6 cultured culture VBN cord-014597-66vd2mdu 1645 7 in in IN cord-014597-66vd2mdu 1645 8 a a DT cord-014597-66vd2mdu 1645 9 2-liter 2-liter CD cord-014597-66vd2mdu 1645 10 bioreactor bioreactor NN cord-014597-66vd2mdu 1645 11 : : : cord-014597-66vd2mdu 1645 12 CHO CHO NNP cord-014597-66vd2mdu 1645 13 - - HYPH cord-014597-66vd2mdu 1645 14 S S NNP cord-014597-66vd2mdu 1645 15 , , , cord-014597-66vd2mdu 1645 16 HEK293SF HEK293SF NNP cord-014597-66vd2mdu 1645 17 and and CC cord-014597-66vd2mdu 1645 18 hybridoma hybridoma NN cord-014597-66vd2mdu 1645 19 KB-26.5 KB-26.5 NNS cord-014597-66vd2mdu 1645 20 . . . cord-014597-66vd2mdu 1646 1 For for IN cord-014597-66vd2mdu 1646 2 the the DT cord-014597-66vd2mdu 1646 3 FBA FBA NNP cord-014597-66vd2mdu 1646 4 , , , cord-014597-66vd2mdu 1646 5 two two CD cord-014597-66vd2mdu 1646 6 adapted adapt VBN cord-014597-66vd2mdu 1646 7 genome genome NN cord-014597-66vd2mdu 1646 8 - - HYPH cord-014597-66vd2mdu 1646 9 scale scale NN cord-014597-66vd2mdu 1646 10 metabolic metabolic JJ cord-014597-66vd2mdu 1646 11 models model NNS cord-014597-66vd2mdu 1646 12 were be VBD cord-014597-66vd2mdu 1646 13 used use VBN cord-014597-66vd2mdu 1646 14 : : : cord-014597-66vd2mdu 1646 15 a a DT cord-014597-66vd2mdu 1646 16 reconstruction reconstruction NN cord-014597-66vd2mdu 1646 17 of of IN cord-014597-66vd2mdu 1646 18 Mus Mus NNP cord-014597-66vd2mdu 1646 19 musculus musculus NN cord-014597-66vd2mdu 1646 20 for for IN cord-014597-66vd2mdu 1646 21 CHO CHO NNP cord-014597-66vd2mdu 1646 22 and and CC cord-014597-66vd2mdu 1646 23 hybridoma hybridoma NN cord-014597-66vd2mdu 1646 24 [ [ -LRB- cord-014597-66vd2mdu 1646 25 3 3 CD cord-014597-66vd2mdu 1646 26 ] ] -RRB- cord-014597-66vd2mdu 1646 27 , , , cord-014597-66vd2mdu 1646 28 and and CC cord-014597-66vd2mdu 1646 29 a a DT cord-014597-66vd2mdu 1646 30 reconstruction reconstruction NN cord-014597-66vd2mdu 1646 31 of of IN cord-014597-66vd2mdu 1646 32 Human human JJ cord-014597-66vd2mdu 1646 33 metabolic metabolic JJ cord-014597-66vd2mdu 1646 34 model model NN cord-014597-66vd2mdu 1646 35 ( ( -LRB- cord-014597-66vd2mdu 1646 36 Recon Recon NNP cord-014597-66vd2mdu 1646 37 2 2 CD cord-014597-66vd2mdu 1646 38 ) ) -RRB- cord-014597-66vd2mdu 1646 39 for for IN cord-014597-66vd2mdu 1646 40 HEK293 HEK293 NNP cord-014597-66vd2mdu 1646 41 [ [ -LRB- cord-014597-66vd2mdu 1646 42 4 4 CD cord-014597-66vd2mdu 1646 43 ] ] -RRB- cord-014597-66vd2mdu 1646 44 . . . cord-014597-66vd2mdu 1647 1 In in IN cord-014597-66vd2mdu 1647 2 cultures culture NNS cord-014597-66vd2mdu 1647 3 where where WRB cord-014597-66vd2mdu 1647 4 pH pH NNP cord-014597-66vd2mdu 1647 5 was be VBD cord-014597-66vd2mdu 1647 6 not not RB cord-014597-66vd2mdu 1647 7 controlled control VBN cord-014597-66vd2mdu 1647 8 , , , cord-014597-66vd2mdu 1647 9 two two CD cord-014597-66vd2mdu 1647 10 different different JJ cord-014597-66vd2mdu 1647 11 metabolic metabolic JJ cord-014597-66vd2mdu 1647 12 phases phase NNS cord-014597-66vd2mdu 1647 13 were be VBD cord-014597-66vd2mdu 1647 14 observed observe VBN cord-014597-66vd2mdu 1647 15 for for IN cord-014597-66vd2mdu 1647 16 CHO CHO NNP cord-014597-66vd2mdu 1647 17 and and CC cord-014597-66vd2mdu 1647 18 HEK293 HEK293 NNP cord-014597-66vd2mdu 1647 19 cells cell NNS cord-014597-66vd2mdu 1647 20 . . . cord-014597-66vd2mdu 1648 1 During during IN cord-014597-66vd2mdu 1648 2 the the DT cord-014597-66vd2mdu 1648 3 first first JJ cord-014597-66vd2mdu 1648 4 phase phase NN cord-014597-66vd2mdu 1648 5 both both DT cord-014597-66vd2mdu 1648 6 cell cell NN cord-014597-66vd2mdu 1648 7 lines line NNS cord-014597-66vd2mdu 1648 8 produced produce VBD cord-014597-66vd2mdu 1648 9 large large JJ cord-014597-66vd2mdu 1648 10 amounts amount NNS cord-014597-66vd2mdu 1648 11 of of IN cord-014597-66vd2mdu 1648 12 lactate lactate NN cord-014597-66vd2mdu 1648 13 as as IN cord-014597-66vd2mdu 1648 14 a a DT cord-014597-66vd2mdu 1648 15 consequence consequence NN cord-014597-66vd2mdu 1648 16 of of IN cord-014597-66vd2mdu 1648 17 the the DT cord-014597-66vd2mdu 1648 18 high high JJ cord-014597-66vd2mdu 1648 19 glucose glucose NN cord-014597-66vd2mdu 1648 20 consumption consumption NN cord-014597-66vd2mdu 1648 21 rates rate NNS cord-014597-66vd2mdu 1648 22 . . . cord-014597-66vd2mdu 1649 1 Interestingly interestingly RB cord-014597-66vd2mdu 1649 2 , , , cord-014597-66vd2mdu 1649 3 when when WRB cord-014597-66vd2mdu 1649 4 pH pH NNP cord-014597-66vd2mdu 1649 5 dropped drop VBD cord-014597-66vd2mdu 1649 6 below below IN cord-014597-66vd2mdu 1649 7 6.8 6.8 CD cord-014597-66vd2mdu 1649 8 , , , cord-014597-66vd2mdu 1649 9 due due JJ cord-014597-66vd2mdu 1649 10 to to IN cord-014597-66vd2mdu 1649 11 acid acid JJ cord-014597-66vd2mdu 1649 12 lactic lactic JJ cord-014597-66vd2mdu 1649 13 secretion secretion NN cord-014597-66vd2mdu 1649 14 and and CC cord-014597-66vd2mdu 1649 15 accumulation accumulation NN cord-014597-66vd2mdu 1649 16 , , , cord-014597-66vd2mdu 1649 17 a a DT cord-014597-66vd2mdu 1649 18 second second JJ cord-014597-66vd2mdu 1649 19 metabolic metabolic JJ cord-014597-66vd2mdu 1649 20 phase phase NN cord-014597-66vd2mdu 1649 21 was be VBD cord-014597-66vd2mdu 1649 22 identified identify VBN cord-014597-66vd2mdu 1649 23 , , , cord-014597-66vd2mdu 1649 24 in in IN cord-014597-66vd2mdu 1649 25 which which WDT cord-014597-66vd2mdu 1649 26 concomitant concomitant JJ cord-014597-66vd2mdu 1649 27 consumption consumption NN cord-014597-66vd2mdu 1649 28 of of IN cord-014597-66vd2mdu 1649 29 glucose glucose NN cord-014597-66vd2mdu 1649 30 and and CC cord-014597-66vd2mdu 1649 31 lactate lactate NN cord-014597-66vd2mdu 1649 32 was be VBD cord-014597-66vd2mdu 1649 33 observed observe VBN cord-014597-66vd2mdu 1649 34 even even RB cord-014597-66vd2mdu 1649 35 during during IN cord-014597-66vd2mdu 1649 36 the the DT cord-014597-66vd2mdu 1649 37 exponential exponential JJ cord-014597-66vd2mdu 1649 38 growth growth NN cord-014597-66vd2mdu 1649 39 phase phase NN cord-014597-66vd2mdu 1649 40 . . . cord-014597-66vd2mdu 1650 1 Conversely conversely RB cord-014597-66vd2mdu 1650 2 , , , cord-014597-66vd2mdu 1650 3 hybridoma hybridoma NN cord-014597-66vd2mdu 1650 4 cells cell NNS cord-014597-66vd2mdu 1650 5 were be VBD cord-014597-66vd2mdu 1650 6 unable unable JJ cord-014597-66vd2mdu 1650 7 to to TO cord-014597-66vd2mdu 1650 8 co co VB cord-014597-66vd2mdu 1650 9 - - VB cord-014597-66vd2mdu 1650 10 consume consume VB cord-014597-66vd2mdu 1650 11 lactate lactate NN cord-014597-66vd2mdu 1650 12 and and CC cord-014597-66vd2mdu 1650 13 glucose glucose NN cord-014597-66vd2mdu 1650 14 simultaneously simultaneously RB cord-014597-66vd2mdu 1650 15 even even RB cord-014597-66vd2mdu 1650 16 under under IN cord-014597-66vd2mdu 1650 17 noncontrolled noncontrolled JJ cord-014597-66vd2mdu 1650 18 pH pH NNP cord-014597-66vd2mdu 1650 19 conditions condition NNS cord-014597-66vd2mdu 1650 20 . . . cord-014597-66vd2mdu 1651 1 Therefore therefore RB cord-014597-66vd2mdu 1651 2 , , , cord-014597-66vd2mdu 1651 3 the the DT cord-014597-66vd2mdu 1651 4 hybridoma hybridoma NN cord-014597-66vd2mdu 1651 5 physiological physiological JJ cord-014597-66vd2mdu 1651 6 data datum NNS cord-014597-66vd2mdu 1651 7 used use VBN cord-014597-66vd2mdu 1651 8 for for IN cord-014597-66vd2mdu 1651 9 the the DT cord-014597-66vd2mdu 1651 10 FBA FBA NNP cord-014597-66vd2mdu 1651 11 corresponded correspond VBD cord-014597-66vd2mdu 1651 12 to to IN cord-014597-66vd2mdu 1651 13 only only RB cord-014597-66vd2mdu 1651 14 phase phase NN cord-014597-66vd2mdu 1651 15 1 1 CD cord-014597-66vd2mdu 1651 16 of of IN cord-014597-66vd2mdu 1651 17 pHcontrolled phcontrolle VBN cord-014597-66vd2mdu 1651 18 cultures culture NNS cord-014597-66vd2mdu 1651 19 . . . cord-014597-66vd2mdu 1652 1 A a DT cord-014597-66vd2mdu 1652 2 summary summary NN cord-014597-66vd2mdu 1652 3 of of IN cord-014597-66vd2mdu 1652 4 the the DT cord-014597-66vd2mdu 1652 5 main main JJ cord-014597-66vd2mdu 1652 6 cell cell NN cord-014597-66vd2mdu 1652 7 growth growth NN cord-014597-66vd2mdu 1652 8 and and CC cord-014597-66vd2mdu 1652 9 metabolic metabolic JJ cord-014597-66vd2mdu 1652 10 parameters parameter NNS cord-014597-66vd2mdu 1652 11 obtained obtain VBN cord-014597-66vd2mdu 1652 12 from from IN cord-014597-66vd2mdu 1652 13 the the DT cord-014597-66vd2mdu 1652 14 different different JJ cord-014597-66vd2mdu 1652 15 experiments experiment NNS cord-014597-66vd2mdu 1652 16 performed perform VBN cord-014597-66vd2mdu 1652 17 is be VBZ cord-014597-66vd2mdu 1652 18 presented present VBN cord-014597-66vd2mdu 1652 19 in in IN cord-014597-66vd2mdu 1652 20 Table Table NNP cord-014597-66vd2mdu 1652 21 1 1 CD cord-014597-66vd2mdu 1652 22 . . . cord-014597-66vd2mdu 1653 1 FBA FBA NNP cord-014597-66vd2mdu 1653 2 shows show VBZ cord-014597-66vd2mdu 1653 3 ( ( -LRB- cord-014597-66vd2mdu 1653 4 Fig Fig NNP cord-014597-66vd2mdu 1653 5 . . . cord-014597-66vd2mdu 1653 6 1 1 CD cord-014597-66vd2mdu 1653 7 for for IN cord-014597-66vd2mdu 1653 8 HEK293 HEK293 NNP cord-014597-66vd2mdu 1653 9 cell cell NN cord-014597-66vd2mdu 1653 10 culture culture NN cord-014597-66vd2mdu 1653 11 ) ) -RRB- cord-014597-66vd2mdu 1653 12 that that IN cord-014597-66vd2mdu 1653 13 lactate lactate NN cord-014597-66vd2mdu 1653 14 is be VBZ cord-014597-66vd2mdu 1653 15 produced produce VBN cord-014597-66vd2mdu 1653 16 in in IN cord-014597-66vd2mdu 1653 17 phase phase NN cord-014597-66vd2mdu 1653 18 1 1 CD cord-014597-66vd2mdu 1653 19 because because IN cord-014597-66vd2mdu 1653 20 pyruvate pyruvate NNP cord-014597-66vd2mdu 1653 21 has have VBZ cord-014597-66vd2mdu 1653 22 to to TO cord-014597-66vd2mdu 1653 23 be be VB cord-014597-66vd2mdu 1653 24 converted convert VBN cord-014597-66vd2mdu 1653 25 to to IN cord-014597-66vd2mdu 1653 26 lactate lactate NN cord-014597-66vd2mdu 1653 27 to to TO cord-014597-66vd2mdu 1653 28 fulfill fulfill VB cord-014597-66vd2mdu 1653 29 the the DT cord-014597-66vd2mdu 1653 30 NADH NADH NNP cord-014597-66vd2mdu 1653 31 regeneration regeneration NN cord-014597-66vd2mdu 1653 32 in in IN cord-014597-66vd2mdu 1653 33 the the DT cord-014597-66vd2mdu 1653 34 cytoplasm cytoplasm NN cord-014597-66vd2mdu 1653 35 and and CC cord-014597-66vd2mdu 1653 36 only only RB cord-014597-66vd2mdu 1653 37 a a DT cord-014597-66vd2mdu 1653 38 small small JJ cord-014597-66vd2mdu 1653 39 amount amount NN cord-014597-66vd2mdu 1653 40 of of IN cord-014597-66vd2mdu 1653 41 pyruvate pyruvate NN cord-014597-66vd2mdu 1653 42 can can MD cord-014597-66vd2mdu 1653 43 be be VB cord-014597-66vd2mdu 1653 44 transported transport VBN cord-014597-66vd2mdu 1653 45 into into IN cord-014597-66vd2mdu 1653 46 TCA TCA NNP cord-014597-66vd2mdu 1653 47 through through IN cord-014597-66vd2mdu 1653 48 Acetyl Acetyl NNP cord-014597-66vd2mdu 1653 49 - - HYPH cord-014597-66vd2mdu 1653 50 CoA. CoA. NNP cord-014597-66vd2mdu 1653 51 Cell Cell NNP cord-014597-66vd2mdu 1653 52 metabolism metabolism NN cord-014597-66vd2mdu 1653 53 in in IN cord-014597-66vd2mdu 1653 54 phase phase NN cord-014597-66vd2mdu 1653 55 1 1 CD cord-014597-66vd2mdu 1653 56 is be VBZ cord-014597-66vd2mdu 1653 57 highly highly RB cord-014597-66vd2mdu 1653 58 inefficient inefficient JJ cord-014597-66vd2mdu 1653 59 , , , cord-014597-66vd2mdu 1653 60 as as IN cord-014597-66vd2mdu 1653 61 the the DT cord-014597-66vd2mdu 1653 62 majority majority NN cord-014597-66vd2mdu 1653 63 of of IN cord-014597-66vd2mdu 1653 64 the the DT cord-014597-66vd2mdu 1653 65 carbon carbon NN cord-014597-66vd2mdu 1653 66 source source NN cord-014597-66vd2mdu 1653 67 is be VBZ cord-014597-66vd2mdu 1653 68 not not RB cord-014597-66vd2mdu 1653 69 used use VBN cord-014597-66vd2mdu 1653 70 for for IN cord-014597-66vd2mdu 1653 71 the the DT cord-014597-66vd2mdu 1653 72 generation generation NN cord-014597-66vd2mdu 1653 73 of of IN cord-014597-66vd2mdu 1653 74 energy energy NN cord-014597-66vd2mdu 1653 75 nor nor CC cord-014597-66vd2mdu 1653 76 biomass biomass NN cord-014597-66vd2mdu 1653 77 . . . cord-014597-66vd2mdu 1654 1 In in IN cord-014597-66vd2mdu 1654 2 phase phase NN cord-014597-66vd2mdu 1654 3 2 2 CD cord-014597-66vd2mdu 1654 4 , , , cord-014597-66vd2mdu 1654 5 in in IN cord-014597-66vd2mdu 1654 6 which which WDT cord-014597-66vd2mdu 1654 7 mitochondrial mitochondrial JJ cord-014597-66vd2mdu 1654 8 LDH LDH NNP cord-014597-66vd2mdu 1654 9 was be VBD cord-014597-66vd2mdu 1654 10 considered consider VBN cord-014597-66vd2mdu 1654 11 , , , cord-014597-66vd2mdu 1654 12 TCA TCA NNP cord-014597-66vd2mdu 1654 13 fluxes flux NNS cord-014597-66vd2mdu 1654 14 could could MD cord-014597-66vd2mdu 1654 15 be be VB cord-014597-66vd2mdu 1654 16 maintained maintain VBN cord-014597-66vd2mdu 1654 17 as as IN cord-014597-66vd2mdu 1654 18 in in IN cord-014597-66vd2mdu 1654 19 phase phase NN cord-014597-66vd2mdu 1654 20 1 1 CD cord-014597-66vd2mdu 1654 21 at at IN cord-014597-66vd2mdu 1654 22 the the DT cord-014597-66vd2mdu 1654 23 maximal maximal JJ cord-014597-66vd2mdu 1654 24 rate rate NN cord-014597-66vd2mdu 1654 25 encountered encounter VBN cord-014597-66vd2mdu 1654 26 ; ; : cord-014597-66vd2mdu 1654 27 hence hence RB cord-014597-66vd2mdu 1654 28 , , , cord-014597-66vd2mdu 1654 29 the the DT cord-014597-66vd2mdu 1654 30 energy energy NN cord-014597-66vd2mdu 1654 31 available available JJ cord-014597-66vd2mdu 1654 32 for for IN cord-014597-66vd2mdu 1654 33 cells cell NNS cord-014597-66vd2mdu 1654 34 to to TO cord-014597-66vd2mdu 1654 35 grow grow VB cord-014597-66vd2mdu 1654 36 was be VBD cord-014597-66vd2mdu 1654 37 similar similar JJ cord-014597-66vd2mdu 1654 38 in in IN cord-014597-66vd2mdu 1654 39 both both DT cord-014597-66vd2mdu 1654 40 phases phase NNS cord-014597-66vd2mdu 1654 41 , , , cord-014597-66vd2mdu 1654 42 obtaining obtain VBG cord-014597-66vd2mdu 1654 43 similar similar JJ cord-014597-66vd2mdu 1654 44 growth growth NN cord-014597-66vd2mdu 1654 45 rate rate NN cord-014597-66vd2mdu 1654 46 . . . cord-014597-66vd2mdu 1655 1 Two two CD cord-014597-66vd2mdu 1655 2 different different JJ cord-014597-66vd2mdu 1655 3 glucose glucose NN cord-014597-66vd2mdu 1655 4 and and CC cord-014597-66vd2mdu 1655 5 lactate lactate NN cord-014597-66vd2mdu 1655 6 metabolism metabolism NN cord-014597-66vd2mdu 1655 7 behaviors behavior NNS cord-014597-66vd2mdu 1655 8 have have VBP cord-014597-66vd2mdu 1655 9 been be VBN cord-014597-66vd2mdu 1655 10 observed observe VBN cord-014597-66vd2mdu 1655 11 in in IN cord-014597-66vd2mdu 1655 12 CHO CHO NNP cord-014597-66vd2mdu 1655 13 and and CC cord-014597-66vd2mdu 1655 14 HEK293 HEK293 NNP cord-014597-66vd2mdu 1655 15 cultures culture NNS cord-014597-66vd2mdu 1655 16 depending depend VBG cord-014597-66vd2mdu 1655 17 on on IN cord-014597-66vd2mdu 1655 18 the the DT cord-014597-66vd2mdu 1655 19 culture culture NN cord-014597-66vd2mdu 1655 20 conditions condition NNS cord-014597-66vd2mdu 1655 21 : : : cord-014597-66vd2mdu 1655 22 phase phase NN cord-014597-66vd2mdu 1655 23 1 1 CD cord-014597-66vd2mdu 1655 24 ) ) -RRB- cord-014597-66vd2mdu 1655 25 glucose glucose NN cord-014597-66vd2mdu 1655 26 consumption consumption NN cord-014597-66vd2mdu 1655 27 and and CC cord-014597-66vd2mdu 1655 28 lactate lactate NN cord-014597-66vd2mdu 1655 29 production production NN cord-014597-66vd2mdu 1655 30 , , , cord-014597-66vd2mdu 1655 31 and and CC cord-014597-66vd2mdu 1655 32 phase phase NN cord-014597-66vd2mdu 1655 33 2 2 CD cord-014597-66vd2mdu 1655 34 ) ) -RRB- cord-014597-66vd2mdu 1655 35 glucose glucose NN cord-014597-66vd2mdu 1655 36 and and CC cord-014597-66vd2mdu 1655 37 lactate lactate VB cord-014597-66vd2mdu 1655 38 simultaneous simultaneous JJ cord-014597-66vd2mdu 1655 39 consumption consumption NN cord-014597-66vd2mdu 1655 40 . . . cord-014597-66vd2mdu 1656 1 In in IN cord-014597-66vd2mdu 1656 2 contrast contrast NN cord-014597-66vd2mdu 1656 3 , , , cord-014597-66vd2mdu 1656 4 only only RB cord-014597-66vd2mdu 1656 5 phase phase NN cord-014597-66vd2mdu 1656 6 1 1 CD cord-014597-66vd2mdu 1656 7 was be VBD cord-014597-66vd2mdu 1656 8 observed observe VBN cord-014597-66vd2mdu 1656 9 in in IN cord-014597-66vd2mdu 1656 10 hybridoma hybridoma NN cord-014597-66vd2mdu 1656 11 cultures culture NNS cord-014597-66vd2mdu 1656 12 even even RB cord-014597-66vd2mdu 1656 13 when when WRB cord-014597-66vd2mdu 1656 14 pH pH NNP cord-014597-66vd2mdu 1656 15 was be VBD cord-014597-66vd2mdu 1656 16 non non JJ cord-014597-66vd2mdu 1656 17 - - VBN cord-014597-66vd2mdu 1656 18 controlled control VBN cord-014597-66vd2mdu 1656 19 . . . cord-014597-66vd2mdu 1657 1 FBA FBA NNP cord-014597-66vd2mdu 1657 2 showed show VBD cord-014597-66vd2mdu 1657 3 that that IN cord-014597-66vd2mdu 1657 4 TCA TCA NNP cord-014597-66vd2mdu 1657 5 fluxes flux NNS cord-014597-66vd2mdu 1657 6 in in IN cord-014597-66vd2mdu 1657 7 phase phase NN cord-014597-66vd2mdu 1657 8 1 1 CD cord-014597-66vd2mdu 1657 9 and and CC cord-014597-66vd2mdu 1657 10 phase phase NN cord-014597-66vd2mdu 1657 11 2 2 CD cord-014597-66vd2mdu 1657 12 were be VBD cord-014597-66vd2mdu 1657 13 similar similar JJ cord-014597-66vd2mdu 1657 14 , , , cord-014597-66vd2mdu 1657 15 obtaining obtain VBG cord-014597-66vd2mdu 1657 16 similar similar JJ cord-014597-66vd2mdu 1657 17 cell cell NN cord-014597-66vd2mdu 1657 18 growth growth NN cord-014597-66vd2mdu 1657 19 rate rate NN cord-014597-66vd2mdu 1657 20 , , , cord-014597-66vd2mdu 1657 21 but but CC cord-014597-66vd2mdu 1657 22 glucose glucose NN cord-014597-66vd2mdu 1657 23 uptake uptake NN cord-014597-66vd2mdu 1657 24 rate rate NN cord-014597-66vd2mdu 1657 25 was be VBD cord-014597-66vd2mdu 1657 26 much much RB cord-014597-66vd2mdu 1657 27 lower low JJR cord-014597-66vd2mdu 1657 28 in in IN cord-014597-66vd2mdu 1657 29 phase phase NN cord-014597-66vd2mdu 1657 30 2 2 CD cord-014597-66vd2mdu 1657 31 due due IN cord-014597-66vd2mdu 1657 32 to to IN cord-014597-66vd2mdu 1657 33 the the DT cord-014597-66vd2mdu 1657 34 lactate lactate NN cord-014597-66vd2mdu 1657 35 co co NN cord-014597-66vd2mdu 1657 36 - - NN cord-014597-66vd2mdu 1657 37 consumption consumption NN cord-014597-66vd2mdu 1657 38 . . . cord-014597-66vd2mdu 1658 1 Some some DT cord-014597-66vd2mdu 1658 2 authors author NNS cord-014597-66vd2mdu 1658 3 hypothesize hypothesize VBP cord-014597-66vd2mdu 1658 4 that that IN cord-014597-66vd2mdu 1658 5 cells cell NNS cord-014597-66vd2mdu 1658 6 metabolize metabolize VBP cord-014597-66vd2mdu 1658 7 extracellular extracellular JJ cord-014597-66vd2mdu 1658 8 lactate lactate NN cord-014597-66vd2mdu 1658 9 as as IN cord-014597-66vd2mdu 1658 10 a a DT cord-014597-66vd2mdu 1658 11 strategy strategy NN cord-014597-66vd2mdu 1658 12 for for IN cord-014597-66vd2mdu 1658 13 pH pH NNP cord-014597-66vd2mdu 1658 14 detoxification detoxification NN cord-014597-66vd2mdu 1658 15 [ [ -LRB- cord-014597-66vd2mdu 1658 16 2 2 CD cord-014597-66vd2mdu 1658 17 ] ] -RRB- cord-014597-66vd2mdu 1658 18 . . . cord-014597-66vd2mdu 1659 1 Glucose glucose NN cord-014597-66vd2mdu 1659 2 and and CC cord-014597-66vd2mdu 1659 3 lactate lactate NN cord-014597-66vd2mdu 1659 4 co co NN cord-014597-66vd2mdu 1659 5 - - NN cord-014597-66vd2mdu 1659 6 metabolization metabolization NN cord-014597-66vd2mdu 1659 7 resulted result VBD cord-014597-66vd2mdu 1659 8 in in IN cord-014597-66vd2mdu 1659 9 a a DT cord-014597-66vd2mdu 1659 10 better well RBR cord-014597-66vd2mdu 1659 11 - - HYPH cord-014597-66vd2mdu 1659 12 balanced balanced JJ cord-014597-66vd2mdu 1659 13 cell cell NN cord-014597-66vd2mdu 1659 14 metabolism metabolism NN cord-014597-66vd2mdu 1659 15 , , , cord-014597-66vd2mdu 1659 16 as as IN cord-014597-66vd2mdu 1659 17 can can MD cord-014597-66vd2mdu 1659 18 be be VB cord-014597-66vd2mdu 1659 19 seen see VBN cord-014597-66vd2mdu 1659 20 from from IN cord-014597-66vd2mdu 1659 21 the the DT cord-014597-66vd2mdu 1659 22 metabolic metabolic JJ cord-014597-66vd2mdu 1659 23 fluxes flux NNS cord-014597-66vd2mdu 1659 24 calculated calculate VBN cord-014597-66vd2mdu 1659 25 , , , cord-014597-66vd2mdu 1659 26 with with IN cord-014597-66vd2mdu 1659 27 minor minor JJ cord-014597-66vd2mdu 1659 28 effects effect NNS cord-014597-66vd2mdu 1659 29 on on IN cord-014597-66vd2mdu 1659 30 cell cell NN cord-014597-66vd2mdu 1659 31 growth growth NN cord-014597-66vd2mdu 1659 32 . . . cord-014597-66vd2mdu 1660 1 The the DT cord-014597-66vd2mdu 1660 2 observation observation NN cord-014597-66vd2mdu 1660 3 of of IN cord-014597-66vd2mdu 1660 4 glucose glucose NN cord-014597-66vd2mdu 1660 5 and and CC cord-014597-66vd2mdu 1660 6 lactate lactate NN cord-014597-66vd2mdu 1660 7 co co NN cord-014597-66vd2mdu 1660 8 - - JJ cord-014597-66vd2mdu 1660 9 consumption consumption JJ cord-014597-66vd2mdu 1660 10 metabolic metabolic JJ cord-014597-66vd2mdu 1660 11 behavior behavior NN cord-014597-66vd2mdu 1660 12 and and CC cord-014597-66vd2mdu 1660 13 its -PRON- PRP$ cord-014597-66vd2mdu 1660 14 deeper deep JJR cord-014597-66vd2mdu 1660 15 study study NN cord-014597-66vd2mdu 1660 16 and and CC cord-014597-66vd2mdu 1660 17 characterization characterization NN cord-014597-66vd2mdu 1660 18 could could MD cord-014597-66vd2mdu 1660 19 open open VB cord-014597-66vd2mdu 1660 20 the the DT cord-014597-66vd2mdu 1660 21 door door NN cord-014597-66vd2mdu 1660 22 of of IN cord-014597-66vd2mdu 1660 23 novel novel NN cord-014597-66vd2mdu 1660 24 culturing culturing NN cord-014597-66vd2mdu 1660 25 strategies strategy NNS cord-014597-66vd2mdu 1660 26 with with IN cord-014597-66vd2mdu 1660 27 the the DT cord-014597-66vd2mdu 1660 28 aim aim NN cord-014597-66vd2mdu 1660 29 of of IN cord-014597-66vd2mdu 1660 30 increasing increase VBG cord-014597-66vd2mdu 1660 31 bioprocesses bioprocesse NNS cord-014597-66vd2mdu 1660 32 productivity productivity NN cord-014597-66vd2mdu 1660 33 . . . cord-014597-66vd2mdu 1661 1 Background Background NNP cord-014597-66vd2mdu 1661 2 Transient transient JJ cord-014597-66vd2mdu 1661 3 protein protein NN cord-014597-66vd2mdu 1661 4 expression expression NN cord-014597-66vd2mdu 1661 5 in in IN cord-014597-66vd2mdu 1661 6 mammalian mammalian JJ cord-014597-66vd2mdu 1661 7 cell cell NN cord-014597-66vd2mdu 1661 8 lines line NNS cord-014597-66vd2mdu 1661 9 has have VBZ cord-014597-66vd2mdu 1661 10 gained gain VBN cord-014597-66vd2mdu 1661 11 increasing increase VBG cord-014597-66vd2mdu 1661 12 relevance relevance NN cord-014597-66vd2mdu 1661 13 as as IN cord-014597-66vd2mdu 1661 14 it -PRON- PRP cord-014597-66vd2mdu 1661 15 enables enable VBZ cord-014597-66vd2mdu 1661 16 fast fast JJ cord-014597-66vd2mdu 1661 17 and and CC cord-014597-66vd2mdu 1661 18 flexible flexible JJ cord-014597-66vd2mdu 1661 19 production production NN cord-014597-66vd2mdu 1661 20 of of IN cord-014597-66vd2mdu 1661 21 high high JJ cord-014597-66vd2mdu 1661 22 - - HYPH cord-014597-66vd2mdu 1661 23 quality quality NN cord-014597-66vd2mdu 1661 24 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 1661 25 protein protein NN cord-014597-66vd2mdu 1661 26 . . . cord-014597-66vd2mdu 1662 1 Considerable considerable JJ cord-014597-66vd2mdu 1662 2 efforts effort NNS cord-014597-66vd2mdu 1662 3 have have VBP cord-014597-66vd2mdu 1662 4 thus thus RB cord-014597-66vd2mdu 1662 5 been be VBN cord-014597-66vd2mdu 1662 6 made make VBN cord-014597-66vd2mdu 1662 7 to to TO cord-014597-66vd2mdu 1662 8 overcome overcome VB cord-014597-66vd2mdu 1662 9 existing exist VBG cord-014597-66vd2mdu 1662 10 limiting limit VBG cord-014597-66vd2mdu 1662 11 aspects aspect NNS cord-014597-66vd2mdu 1662 12 of of IN cord-014597-66vd2mdu 1662 13 transient transient JJ cord-014597-66vd2mdu 1662 14 gene gene NN cord-014597-66vd2mdu 1662 15 expression expression NN cord-014597-66vd2mdu 1662 16 systems system NNS cord-014597-66vd2mdu 1662 17 , , , cord-014597-66vd2mdu 1662 18 in in IN cord-014597-66vd2mdu 1662 19 terms term NNS cord-014597-66vd2mdu 1662 20 of of IN cord-014597-66vd2mdu 1662 21 cell cell NN cord-014597-66vd2mdu 1662 22 lines line NNS cord-014597-66vd2mdu 1662 23 , , , cord-014597-66vd2mdu 1662 24 cell cell NN cord-014597-66vd2mdu 1662 25 culture culture NN cord-014597-66vd2mdu 1662 26 - - HYPH cord-014597-66vd2mdu 1662 27 based base VBN cord-014597-66vd2mdu 1662 28 systems system NNS cord-014597-66vd2mdu 1662 29 , , , cord-014597-66vd2mdu 1662 30 and and CC cord-014597-66vd2mdu 1662 31 protein protein NN cord-014597-66vd2mdu 1662 32 production production NN cord-014597-66vd2mdu 1662 33 in in IN cord-014597-66vd2mdu 1662 34 a a DT cord-014597-66vd2mdu 1662 35 cost cost NN cord-014597-66vd2mdu 1662 36 - - HYPH cord-014597-66vd2mdu 1662 37 effective effective JJ cord-014597-66vd2mdu 1662 38 manner manner NN cord-014597-66vd2mdu 1662 39 . . . cord-014597-66vd2mdu 1663 1 Milligram milligram NN cord-014597-66vd2mdu 1663 2 amounts amount NNS cord-014597-66vd2mdu 1663 3 of of IN cord-014597-66vd2mdu 1663 4 protein protein NN cord-014597-66vd2mdu 1663 5 per per IN cord-014597-66vd2mdu 1663 6 liter liter NN cord-014597-66vd2mdu 1663 7 can can MD cord-014597-66vd2mdu 1663 8 be be VB cord-014597-66vd2mdu 1663 9 produced produce VBN cord-014597-66vd2mdu 1663 10 within within IN cord-014597-66vd2mdu 1663 11 several several JJ cord-014597-66vd2mdu 1663 12 days day NNS cord-014597-66vd2mdu 1663 13 , , , cord-014597-66vd2mdu 1663 14 allowing allow VBG cord-014597-66vd2mdu 1663 15 a a DT cord-014597-66vd2mdu 1663 16 significant significant JJ cord-014597-66vd2mdu 1663 17 shortening shortening NN cord-014597-66vd2mdu 1663 18 of of IN cord-014597-66vd2mdu 1663 19 the the DT cord-014597-66vd2mdu 1663 20 bioproduction bioproduction NN cord-014597-66vd2mdu 1663 21 process process NN cord-014597-66vd2mdu 1663 22 in in IN cord-014597-66vd2mdu 1663 23 comparison comparison NN cord-014597-66vd2mdu 1663 24 to to IN cord-014597-66vd2mdu 1663 25 protein protein NN cord-014597-66vd2mdu 1663 26 production production NN cord-014597-66vd2mdu 1663 27 from from IN cord-014597-66vd2mdu 1663 28 stable stable JJ cord-014597-66vd2mdu 1663 29 clones clone NNS cord-014597-66vd2mdu 1663 30 . . . cord-014597-66vd2mdu 1664 1 To to TO cord-014597-66vd2mdu 1664 2 ensure ensure VB cord-014597-66vd2mdu 1664 3 the the DT cord-014597-66vd2mdu 1664 4 robustness robustness NN cord-014597-66vd2mdu 1664 5 of of IN cord-014597-66vd2mdu 1664 6 the the DT cord-014597-66vd2mdu 1664 7 process process NN cord-014597-66vd2mdu 1664 8 , , , cord-014597-66vd2mdu 1664 9 it -PRON- PRP cord-014597-66vd2mdu 1664 10 is be VBZ cord-014597-66vd2mdu 1664 11 essential essential JJ cord-014597-66vd2mdu 1664 12 to to TO cord-014597-66vd2mdu 1664 13 have have VB cord-014597-66vd2mdu 1664 14 a a DT cord-014597-66vd2mdu 1664 15 reliable reliable JJ cord-014597-66vd2mdu 1664 16 and and CC cord-014597-66vd2mdu 1664 17 easy easy JJ cord-014597-66vd2mdu 1664 18 - - HYPH cord-014597-66vd2mdu 1664 19 to to IN cord-014597-66vd2mdu 1664 20 - - HYPH cord-014597-66vd2mdu 1664 21 use use NN cord-014597-66vd2mdu 1664 22 transfection transfection NN cord-014597-66vd2mdu 1664 23 method method NN cord-014597-66vd2mdu 1664 24 . . . cord-014597-66vd2mdu 1665 1 To to TO cord-014597-66vd2mdu 1665 2 palliate palliate VB cord-014597-66vd2mdu 1665 3 for for IN cord-014597-66vd2mdu 1665 4 the the DT cord-014597-66vd2mdu 1665 5 need need NN cord-014597-66vd2mdu 1665 6 of of IN cord-014597-66vd2mdu 1665 7 a a DT cord-014597-66vd2mdu 1665 8 reliable reliable JJ cord-014597-66vd2mdu 1665 9 transfection transfection NN cord-014597-66vd2mdu 1665 10 reagent reagent NN cord-014597-66vd2mdu 1665 11 , , , cord-014597-66vd2mdu 1665 12 we -PRON- PRP cord-014597-66vd2mdu 1665 13 developed develop VBD cord-014597-66vd2mdu 1666 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 1666 2 ® ® NNPS cord-014597-66vd2mdu 1666 3 , , , cord-014597-66vd2mdu 1666 4 the the DT cord-014597-66vd2mdu 1666 5 only only JJ cord-014597-66vd2mdu 1666 6 commercially commercially RB cord-014597-66vd2mdu 1666 7 available available JJ cord-014597-66vd2mdu 1666 8 PEI PEI NNP cord-014597-66vd2mdu 1666 9 optimised optimise VBD cord-014597-66vd2mdu 1666 10 for for IN cord-014597-66vd2mdu 1666 11 mid mid JJ cord-014597-66vd2mdu 1666 12 to to IN cord-014597-66vd2mdu 1666 13 large large JJ cord-014597-66vd2mdu 1666 14 - - HYPH cord-014597-66vd2mdu 1666 15 scale scale NN cord-014597-66vd2mdu 1666 16 transient transient JJ cord-014597-66vd2mdu 1666 17 protein protein NN cord-014597-66vd2mdu 1666 18 production production NN cord-014597-66vd2mdu 1666 19 during during IN cord-014597-66vd2mdu 1666 20 process process NN cord-014597-66vd2mdu 1666 21 development development NN cord-014597-66vd2mdu 1666 22 . . . cord-014597-66vd2mdu 1667 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 1668 1 ® ® NNP cord-014597-66vd2mdu 1668 2 is be VBZ cord-014597-66vd2mdu 1668 3 a a DT cord-014597-66vd2mdu 1668 4 non non JJ cord-014597-66vd2mdu 1668 5 - - JJ cord-014597-66vd2mdu 1668 6 polydiperse polydiperse JJ cord-014597-66vd2mdu 1668 7 and and CC cord-014597-66vd2mdu 1668 8 fully fully RB cord-014597-66vd2mdu 1668 9 - - HYPH cord-014597-66vd2mdu 1668 10 characterised characterise VBN cord-014597-66vd2mdu 1668 11 polymer polymer NN cord-014597-66vd2mdu 1668 12 that that WDT cord-014597-66vd2mdu 1668 13 has have VBZ cord-014597-66vd2mdu 1668 14 become become VBN cord-014597-66vd2mdu 1668 15 the the DT cord-014597-66vd2mdu 1668 16 gold gold NN cord-014597-66vd2mdu 1668 17 PEI PEI NNP cord-014597-66vd2mdu 1668 18 standard standard NN cord-014597-66vd2mdu 1668 19 due due IN cord-014597-66vd2mdu 1668 20 to to IN cord-014597-66vd2mdu 1668 21 its -PRON- PRP$ cord-014597-66vd2mdu 1668 22 reliability reliability NN cord-014597-66vd2mdu 1668 23 , , , cord-014597-66vd2mdu 1668 24 reproducibility reproducibility NN cord-014597-66vd2mdu 1668 25 in in IN cord-014597-66vd2mdu 1668 26 high high JJ cord-014597-66vd2mdu 1668 27 DNA dna NN cord-014597-66vd2mdu 1668 28 delivery delivery NN cord-014597-66vd2mdu 1668 29 efficiency efficiency NN cord-014597-66vd2mdu 1668 30 and and CC cord-014597-66vd2mdu 1668 31 in in IN cord-014597-66vd2mdu 1668 32 ensuing ensue VBG cord-014597-66vd2mdu 1668 33 high high JJ cord-014597-66vd2mdu 1668 34 protein protein NN cord-014597-66vd2mdu 1668 35 production production NN cord-014597-66vd2mdu 1668 36 yields yield NNS cord-014597-66vd2mdu 1668 37 . . . cord-014597-66vd2mdu 1669 1 Here here RB cord-014597-66vd2mdu 1669 2 , , , cord-014597-66vd2mdu 1669 3 we -PRON- PRP cord-014597-66vd2mdu 1669 4 present present VBP cord-014597-66vd2mdu 1669 5 experimental experimental JJ cord-014597-66vd2mdu 1669 6 data datum NNS cord-014597-66vd2mdu 1669 7 showing show VBG cord-014597-66vd2mdu 1669 8 the the DT cord-014597-66vd2mdu 1669 9 benefits benefit NNS cord-014597-66vd2mdu 1669 10 of of IN cord-014597-66vd2mdu 1669 11 using use VBG cord-014597-66vd2mdu 1669 12 PEIpro PEIpro NNP cord-014597-66vd2mdu 1669 13 ® ® NNP cord-014597-66vd2mdu 1669 14 for for IN cord-014597-66vd2mdu 1669 15 protein protein NN cord-014597-66vd2mdu 1669 16 production production NN cord-014597-66vd2mdu 1669 17 in in IN cord-014597-66vd2mdu 1669 18 comparison comparison NN cord-014597-66vd2mdu 1669 19 to to IN cord-014597-66vd2mdu 1669 20 other other JJ cord-014597-66vd2mdu 1669 21 PEIs pei NNS cord-014597-66vd2mdu 1669 22 . . . cord-014597-66vd2mdu 1670 1 We -PRON- PRP cord-014597-66vd2mdu 1670 2 further further RB cord-014597-66vd2mdu 1670 3 demonstrate demonstrate VBP cord-014597-66vd2mdu 1670 4 compatibility compatibility NN cord-014597-66vd2mdu 1670 5 of of IN cord-014597-66vd2mdu 1670 6 using use VBG cord-014597-66vd2mdu 1670 7 PEIpro PEIpro NNP cord-014597-66vd2mdu 1670 8 ® ® NNP cord-014597-66vd2mdu 1670 9 for for IN cord-014597-66vd2mdu 1670 10 recombinant recombinant JJ cord-014597-66vd2mdu 1670 11 protein protein NN cord-014597-66vd2mdu 1670 12 production production NN cord-014597-66vd2mdu 1670 13 in in IN cord-014597-66vd2mdu 1670 14 most most RBS cord-014597-66vd2mdu 1670 15 commonly commonly RB cord-014597-66vd2mdu 1670 16 used use VBN cord-014597-66vd2mdu 1670 17 chemicallydefined chemicallydefined JJ cord-014597-66vd2mdu 1670 18 media medium NNS cord-014597-66vd2mdu 1670 19 . . . cord-014597-66vd2mdu 1671 1 Materiel materiel NN cord-014597-66vd2mdu 1671 2 and and CC cord-014597-66vd2mdu 1671 3 methods method NNS cord-014597-66vd2mdu 1671 4 Suspension Suspension NNP cord-014597-66vd2mdu 1671 5 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1671 6 and and CC cord-014597-66vd2mdu 1671 7 CHO CHO NNP cord-014597-66vd2mdu 1671 8 cells cell NNS cord-014597-66vd2mdu 1671 9 were be VBD cord-014597-66vd2mdu 1671 10 cultured culture VBN cord-014597-66vd2mdu 1671 11 in in IN cord-014597-66vd2mdu 1671 12 shaker shaker NN cord-014597-66vd2mdu 1671 13 flasks flask NNS cord-014597-66vd2mdu 1671 14 in in IN cord-014597-66vd2mdu 1671 15 various various JJ cord-014597-66vd2mdu 1671 16 synthetic synthetic JJ cord-014597-66vd2mdu 1671 17 media medium NNS cord-014597-66vd2mdu 1671 18 , , , cord-014597-66vd2mdu 1671 19 as as IN cord-014597-66vd2mdu 1671 20 listed list VBN cord-014597-66vd2mdu 1671 21 in in IN cord-014597-66vd2mdu 1671 22 Table Table NNP cord-014597-66vd2mdu 1671 23 1 1 CD cord-014597-66vd2mdu 1671 24 . . . cord-014597-66vd2mdu 1672 1 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1673 1 and and CC cord-014597-66vd2mdu 1673 2 CHO CHO NNP cord-014597-66vd2mdu 1673 3 cells cell NNS cord-014597-66vd2mdu 1673 4 were be VBD cord-014597-66vd2mdu 1673 5 resuspended resuspend VBN cord-014597-66vd2mdu 1673 6 at at IN cord-014597-66vd2mdu 1673 7 1×10 1×10 CD cord-014597-66vd2mdu 1673 8 6 6 CD cord-014597-66vd2mdu 1673 9 cells cell NNS cord-014597-66vd2mdu 1673 10 / / SYM cord-014597-66vd2mdu 1673 11 ml ml NNS cord-014597-66vd2mdu 1673 12 of of IN cord-014597-66vd2mdu 1673 13 serum serum NN cord-014597-66vd2mdu 1673 14 - - HYPH cord-014597-66vd2mdu 1673 15 free free JJ cord-014597-66vd2mdu 1673 16 medium medium NN cord-014597-66vd2mdu 1673 17 , , , cord-014597-66vd2mdu 1673 18 on on IN cord-014597-66vd2mdu 1673 19 the the DT cord-014597-66vd2mdu 1673 20 day day NN cord-014597-66vd2mdu 1673 21 before before IN cord-014597-66vd2mdu 1673 22 transfection transfection NN cord-014597-66vd2mdu 1673 23 . . . cord-014597-66vd2mdu 1674 1 Cells cell NNS cord-014597-66vd2mdu 1674 2 were be VBD cord-014597-66vd2mdu 1674 3 transfected transfecte VBN cord-014597-66vd2mdu 1674 4 with with IN cord-014597-66vd2mdu 1674 5 0.5 0.5 CD cord-014597-66vd2mdu 1674 6 - - SYM cord-014597-66vd2mdu 1674 7 1 1 CD cord-014597-66vd2mdu 1674 8 mg mg NN cord-014597-66vd2mdu 1674 9 of of IN cord-014597-66vd2mdu 1674 10 plasmid plasmid NN cord-014597-66vd2mdu 1674 11 DNA dna NN cord-014597-66vd2mdu 1674 12 encoding encoding NN cord-014597-66vd2mdu 1674 13 for for IN cord-014597-66vd2mdu 1674 14 the the DT cord-014597-66vd2mdu 1674 15 Luciferase Luciferase NNP cord-014597-66vd2mdu 1674 16 gene gene NN cord-014597-66vd2mdu 1674 17 reporter reporter NN cord-014597-66vd2mdu 1674 18 using use VBG cord-014597-66vd2mdu 1674 19 PEIpro PEIpro NNP cord-014597-66vd2mdu 1674 20 ® ® NNPS cord-014597-66vd2mdu 1674 21 , , , cord-014597-66vd2mdu 1674 22 PEI PEI NNP cord-014597-66vd2mdu 1674 23 " " `` cord-014597-66vd2mdu 1674 24 Max Max NNP cord-014597-66vd2mdu 1674 25 " " '' cord-014597-66vd2mdu 1674 26 and and CC cord-014597-66vd2mdu 1674 27 L L NNP cord-014597-66vd2mdu 1674 28 - - HYPH cord-014597-66vd2mdu 1674 29 PEI PEI NNP cord-014597-66vd2mdu 1674 30 25 25 CD cord-014597-66vd2mdu 1674 31 kDa kDa NNS cord-014597-66vd2mdu 1675 1 ( ( -LRB- cord-014597-66vd2mdu 1675 2 Polysciences Polysciences NNP cord-014597-66vd2mdu 1675 3 , , , cord-014597-66vd2mdu 1675 4 Warrington Warrington NNP cord-014597-66vd2mdu 1675 5 , , , cord-014597-66vd2mdu 1675 6 PA PA NNP cord-014597-66vd2mdu 1675 7 ) ) -RRB- cord-014597-66vd2mdu 1675 8 resuspended resuspend VBD cord-014597-66vd2mdu 1675 9 at at IN cord-014597-66vd2mdu 1675 10 1 1 CD cord-014597-66vd2mdu 1675 11 mg mg NNP cord-014597-66vd2mdu 1675 12 / / SYM cord-014597-66vd2mdu 1675 13 ml ml NN cord-014597-66vd2mdu 1675 14 according accord VBG cord-014597-66vd2mdu 1675 15 to to IN cord-014597-66vd2mdu 1675 16 the the DT cord-014597-66vd2mdu 1675 17 manufacturer manufacturer NN cord-014597-66vd2mdu 1675 18 's 's POS cord-014597-66vd2mdu 1675 19 recommendation recommendation NN cord-014597-66vd2mdu 1675 20 . . . cord-014597-66vd2mdu 1676 1 Protein protein NN cord-014597-66vd2mdu 1676 2 expression expression NN cord-014597-66vd2mdu 1676 3 of of IN cord-014597-66vd2mdu 1676 4 the the DT cord-014597-66vd2mdu 1676 5 luciferase luciferase NN cord-014597-66vd2mdu 1676 6 reporter reporter NN cord-014597-66vd2mdu 1676 7 gene gene NN cord-014597-66vd2mdu 1676 8 was be VBD cord-014597-66vd2mdu 1676 9 assayed assay VBN cord-014597-66vd2mdu 1676 10 48 48 CD cord-014597-66vd2mdu 1676 11 hours hour NNS cord-014597-66vd2mdu 1676 12 post post NN cord-014597-66vd2mdu 1676 13 - - NN cord-014597-66vd2mdu 1676 14 transfection transfection NN cord-014597-66vd2mdu 1676 15 by by IN cord-014597-66vd2mdu 1676 16 affinity affinity NN cord-014597-66vd2mdu 1676 17 chromatography chromatography NN cord-014597-66vd2mdu 1676 18 using use VBG cord-014597-66vd2mdu 1676 19 protein protein NN cord-014597-66vd2mdu 1676 20 G G NNP cord-014597-66vd2mdu 1676 21 ( ( -LRB- cord-014597-66vd2mdu 1676 22 HPLC HPLC NNP cord-014597-66vd2mdu 1676 23 ) ) -RRB- cord-014597-66vd2mdu 1676 24 . . . cord-014597-66vd2mdu 1677 1 Comparison comparison NN cord-014597-66vd2mdu 1677 2 of of IN cord-014597-66vd2mdu 1677 3 PEIpro PEIpro NNP cord-014597-66vd2mdu 1678 1 ® ® VB cord-014597-66vd2mdu 1678 2 to to IN cord-014597-66vd2mdu 1678 3 other other JJ cord-014597-66vd2mdu 1678 4 commercially commercially RB cord-014597-66vd2mdu 1678 5 available available JJ cord-014597-66vd2mdu 1678 6 PEIs pei NNS cord-014597-66vd2mdu 1678 7 was be VBD cord-014597-66vd2mdu 1678 8 achieved achieve VBN cord-014597-66vd2mdu 1678 9 by by IN cord-014597-66vd2mdu 1678 10 transfecting transfecte VBG cord-014597-66vd2mdu 1678 11 suspension suspension NN cord-014597-66vd2mdu 1679 1 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1679 2 and and CC cord-014597-66vd2mdu 1679 3 CHO CHO NNP cord-014597-66vd2mdu 1679 4 cells cell NNS cord-014597-66vd2mdu 1679 5 with with IN cord-014597-66vd2mdu 1679 6 plasmid plasmid NN cord-014597-66vd2mdu 1679 7 DNA dna NN cord-014597-66vd2mdu 1679 8 encoding encoding NN cord-014597-66vd2mdu 1679 9 for for IN cord-014597-66vd2mdu 1679 10 the the DT cord-014597-66vd2mdu 1679 11 luciferase luciferase NN cord-014597-66vd2mdu 1679 12 gene gene NN cord-014597-66vd2mdu 1679 13 reporter reporter NN cord-014597-66vd2mdu 1679 14 . . . cord-014597-66vd2mdu 1680 1 Luciferase luciferase NN cord-014597-66vd2mdu 1680 2 production production NN cord-014597-66vd2mdu 1680 3 yields yield NNS cord-014597-66vd2mdu 1680 4 obtained obtain VBN cord-014597-66vd2mdu 1680 5 in in IN cord-014597-66vd2mdu 1680 6 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1680 7 and and CC cord-014597-66vd2mdu 1680 8 CHO CHO NNP cord-014597-66vd2mdu 1680 9 cells cell NNS cord-014597-66vd2mdu 1680 10 were be VBD cord-014597-66vd2mdu 1680 11 at at IN cord-014597-66vd2mdu 1680 12 least least JJS cord-014597-66vd2mdu 1680 13 respectively respectively RB cord-014597-66vd2mdu 1680 14 5-fold 5-fold CD cord-014597-66vd2mdu 1680 15 and and CC cord-014597-66vd2mdu 1680 16 10-fold 10-fold JJ cord-014597-66vd2mdu 1680 17 higher high JJR cord-014597-66vd2mdu 1680 18 when when WRB cord-014597-66vd2mdu 1680 19 using use VBG cord-014597-66vd2mdu 1680 20 a a DT cord-014597-66vd2mdu 1680 21 similar similar JJ cord-014597-66vd2mdu 1680 22 amount amount NN cord-014597-66vd2mdu 1680 23 of of IN cord-014597-66vd2mdu 1680 24 PEIpro PEIpro NNP cord-014597-66vd2mdu 1680 25 in in IN cord-014597-66vd2mdu 1680 26 comparison comparison NN cord-014597-66vd2mdu 1680 27 to to IN cord-014597-66vd2mdu 1680 28 the the DT cord-014597-66vd2mdu 1680 29 other other JJ cord-014597-66vd2mdu 1680 30 PEIs pei NNS cord-014597-66vd2mdu 1680 31 ( ( -LRB- cord-014597-66vd2mdu 1680 32 Fig fig NN cord-014597-66vd2mdu 1680 33 . . . cord-014597-66vd2mdu 1680 34 1 1 CD cord-014597-66vd2mdu 1680 35 ) ) -RRB- cord-014597-66vd2mdu 1680 36 . . . cord-014597-66vd2mdu 1681 1 Furthermore furthermore RB cord-014597-66vd2mdu 1681 2 , , , cord-014597-66vd2mdu 1681 3 PEIpro PEIpro NNP cord-014597-66vd2mdu 1681 4 ® ® NNP cord-014597-66vd2mdu 1681 5 was be VBD cord-014597-66vd2mdu 1681 6 the the DT cord-014597-66vd2mdu 1681 7 only only JJ cord-014597-66vd2mdu 1681 8 PEI PEI NNP cord-014597-66vd2mdu 1681 9 that that WDT cord-014597-66vd2mdu 1681 10 led lead VBD cord-014597-66vd2mdu 1681 11 to to IN cord-014597-66vd2mdu 1681 12 similar similar JJ cord-014597-66vd2mdu 1681 13 luciferase luciferase NN cord-014597-66vd2mdu 1681 14 production production NN cord-014597-66vd2mdu 1681 15 yields yield NNS cord-014597-66vd2mdu 1681 16 when when WRB cord-014597-66vd2mdu 1681 17 decreasing decrease VBG cord-014597-66vd2mdu 1681 18 the the DT cord-014597-66vd2mdu 1681 19 amount amount NN cord-014597-66vd2mdu 1681 20 of of IN cord-014597-66vd2mdu 1681 21 plasmid plasmid NN cord-014597-66vd2mdu 1681 22 DNA dna NN cord-014597-66vd2mdu 1681 23 per per IN cord-014597-66vd2mdu 1681 24 Liter liter NN cord-014597-66vd2mdu 1681 25 of of IN cord-014597-66vd2mdu 1681 26 cell cell NN cord-014597-66vd2mdu 1681 27 culture culture NN cord-014597-66vd2mdu 1681 28 . . . cord-014597-66vd2mdu 1682 1 Conversely conversely RB cord-014597-66vd2mdu 1682 2 , , , cord-014597-66vd2mdu 1682 3 at at IN cord-014597-66vd2mdu 1682 4 least least JJS cord-014597-66vd2mdu 1682 5 1 1 CD cord-014597-66vd2mdu 1682 6 mg mg NN cord-014597-66vd2mdu 1682 7 of of IN cord-014597-66vd2mdu 1682 8 plasmid plasmid NN cord-014597-66vd2mdu 1682 9 DNA dna NN cord-014597-66vd2mdu 1682 10 and and CC cord-014597-66vd2mdu 1682 11 4-fold 4-fold CD cord-014597-66vd2mdu 1682 12 more more JJR cord-014597-66vd2mdu 1682 13 of of IN cord-014597-66vd2mdu 1682 14 PEI PEI NNP cord-014597-66vd2mdu 1682 15 " " `` cord-014597-66vd2mdu 1682 16 Max Max NNP cord-014597-66vd2mdu 1682 17 " " '' cord-014597-66vd2mdu 1682 18 and and CC cord-014597-66vd2mdu 1682 19 L L NNP cord-014597-66vd2mdu 1682 20 - - HYPH cord-014597-66vd2mdu 1682 21 PEI PEI NNP cord-014597-66vd2mdu 1682 22 25 25 CD cord-014597-66vd2mdu 1682 23 kDa kDa NNPS cord-014597-66vd2mdu 1682 24 were be VBD cord-014597-66vd2mdu 1682 25 needed need VBN cord-014597-66vd2mdu 1682 26 to to TO cord-014597-66vd2mdu 1682 27 obtain obtain VB cord-014597-66vd2mdu 1682 28 a a DT cord-014597-66vd2mdu 1682 29 similar similar JJ cord-014597-66vd2mdu 1682 30 Luciferase Luciferase NNP cord-014597-66vd2mdu 1682 31 expression expression NN cord-014597-66vd2mdu 1682 32 range range NN cord-014597-66vd2mdu 1682 33 in in IN cord-014597-66vd2mdu 1682 34 both both CC cord-014597-66vd2mdu 1682 35 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1682 36 and and CC cord-014597-66vd2mdu 1682 37 CHO CHO NNP cord-014597-66vd2mdu 1682 38 cells cell NNS cord-014597-66vd2mdu 1682 39 . . . cord-014597-66vd2mdu 1683 1 We -PRON- PRP cord-014597-66vd2mdu 1683 2 further further RB cord-014597-66vd2mdu 1683 3 assessed assess VBD cord-014597-66vd2mdu 1683 4 the the DT cord-014597-66vd2mdu 1683 5 compatibility compatibility NN cord-014597-66vd2mdu 1683 6 and and CC cord-014597-66vd2mdu 1683 7 versatility versatility NN cord-014597-66vd2mdu 1683 8 of of IN cord-014597-66vd2mdu 1683 9 PEIpro PEIpro NNP cord-014597-66vd2mdu 1684 1 ® ® VBN cord-014597-66vd2mdu 1684 2 by by IN cord-014597-66vd2mdu 1684 3 measuring measure VBG cord-014597-66vd2mdu 1684 4 protein protein NN cord-014597-66vd2mdu 1684 5 production production NN cord-014597-66vd2mdu 1684 6 yields yield NNS cord-014597-66vd2mdu 1684 7 obtained obtain VBN cord-014597-66vd2mdu 1684 8 in in IN cord-014597-66vd2mdu 1684 9 most most RBS cord-014597-66vd2mdu 1684 10 commonly commonly RB cord-014597-66vd2mdu 1684 11 used use VBN cord-014597-66vd2mdu 1684 12 animal animal NN cord-014597-66vd2mdu 1684 13 - - HYPH cord-014597-66vd2mdu 1684 14 free free JJ cord-014597-66vd2mdu 1684 15 synthetic synthetic JJ cord-014597-66vd2mdu 1684 16 media medium NNS cord-014597-66vd2mdu 1684 17 . . . cord-014597-66vd2mdu 1685 1 As as IN cord-014597-66vd2mdu 1685 2 shown show VBN cord-014597-66vd2mdu 1685 3 in in IN cord-014597-66vd2mdu 1685 4 Fig Fig NNP cord-014597-66vd2mdu 1685 5 . . . cord-014597-66vd2mdu 1686 1 2 2 LS cord-014597-66vd2mdu 1686 2 , , , cord-014597-66vd2mdu 1686 3 PEIpro PEIpro NNP cord-014597-66vd2mdu 1686 4 ® ® NNP cord-014597-66vd2mdu 1686 5 leads lead NNS cord-014597-66vd2mdu 1686 6 to to IN cord-014597-66vd2mdu 1686 7 high high JJ cord-014597-66vd2mdu 1686 8 protein protein NN cord-014597-66vd2mdu 1686 9 production production NN cord-014597-66vd2mdu 1686 10 yieds yied NNS cord-014597-66vd2mdu 1686 11 in in IN cord-014597-66vd2mdu 1686 12 several several JJ cord-014597-66vd2mdu 1686 13 commercially commercially RB cord-014597-66vd2mdu 1686 14 avaialble avaialble JJ cord-014597-66vd2mdu 1686 15 media medium NNS cord-014597-66vd2mdu 1686 16 formulations formulation NNS cord-014597-66vd2mdu 1686 17 for for IN cord-014597-66vd2mdu 1686 18 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1686 19 anc anc NNP cord-014597-66vd2mdu 1686 20 CHO CHO NNP cord-014597-66vd2mdu 1686 21 cell cell NN cord-014597-66vd2mdu 1686 22 lines line NNS cord-014597-66vd2mdu 1686 23 . . . cord-014597-66vd2mdu 1687 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 1688 1 ® ® NNP cord-014597-66vd2mdu 1688 2 is be VBZ cord-014597-66vd2mdu 1688 3 the the DT cord-014597-66vd2mdu 1688 4 only only JJ cord-014597-66vd2mdu 1688 5 fully fully RB cord-014597-66vd2mdu 1688 6 characterised characterise VBN cord-014597-66vd2mdu 1688 7 PEI PEI NNP cord-014597-66vd2mdu 1688 8 transfection transfection NN cord-014597-66vd2mdu 1688 9 reagent reagent NN cord-014597-66vd2mdu 1688 10 that that WDT cord-014597-66vd2mdu 1688 11 is be VBZ cord-014597-66vd2mdu 1688 12 suitable suitable JJ cord-014597-66vd2mdu 1688 13 for for IN cord-014597-66vd2mdu 1688 14 reliable reliable JJ cord-014597-66vd2mdu 1688 15 and and CC cord-014597-66vd2mdu 1688 16 reproducible reproducible JJ cord-014597-66vd2mdu 1688 17 recombinant recombinant JJ cord-014597-66vd2mdu 1688 18 protein protein NN cord-014597-66vd2mdu 1688 19 production production NN cord-014597-66vd2mdu 1688 20 , , , cord-014597-66vd2mdu 1688 21 irrespective irrespective RB cord-014597-66vd2mdu 1688 22 of of IN cord-014597-66vd2mdu 1688 23 the the DT cord-014597-66vd2mdu 1688 24 scale scale NN cord-014597-66vd2mdu 1688 25 of of IN cord-014597-66vd2mdu 1688 26 production production NN cord-014597-66vd2mdu 1688 27 and and CC cord-014597-66vd2mdu 1688 28 of of IN cord-014597-66vd2mdu 1688 29 the the DT cord-014597-66vd2mdu 1688 30 type type NN cord-014597-66vd2mdu 1688 31 of of IN cord-014597-66vd2mdu 1688 32 adherent adherent NN cord-014597-66vd2mdu 1688 33 and and CC cord-014597-66vd2mdu 1688 34 suspension suspension NN cord-014597-66vd2mdu 1688 35 cell cell NN cord-014597-66vd2mdu 1688 36 culture culture NN cord-014597-66vd2mdu 1688 37 system system NN cord-014597-66vd2mdu 1688 38 . . . cord-014597-66vd2mdu 1689 1 Fig Fig NNP cord-014597-66vd2mdu 1689 2 . . . cord-014597-66vd2mdu 1689 3 1 1 CD cord-014597-66vd2mdu 1689 4 ( ( -LRB- cord-014597-66vd2mdu 1689 5 abstract abstract JJ cord-014597-66vd2mdu 1689 6 P-274 p-274 NN cord-014597-66vd2mdu 1689 7 ) ) -RRB- cord-014597-66vd2mdu 1689 8 . . . cord-014597-66vd2mdu 1690 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 1690 2 ® ® NNP cord-014597-66vd2mdu 1690 3 requires require VBZ cord-014597-66vd2mdu 1690 4 less less RBR cord-014597-66vd2mdu 1690 5 reagent reagent JJ cord-014597-66vd2mdu 1690 6 and and CC cord-014597-66vd2mdu 1690 7 similar similar JJ cord-014597-66vd2mdu 1690 8 to to IN cord-014597-66vd2mdu 1690 9 lower low JJR cord-014597-66vd2mdu 1690 10 DNA dna NN cord-014597-66vd2mdu 1690 11 amount amount NN cord-014597-66vd2mdu 1690 12 compared compare VBN cord-014597-66vd2mdu 1690 13 to to IN cord-014597-66vd2mdu 1690 14 other other JJ cord-014597-66vd2mdu 1690 15 PEIs pei NNS cord-014597-66vd2mdu 1690 16 . . . cord-014597-66vd2mdu 1691 1 Suspension suspension NN cord-014597-66vd2mdu 1691 2 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1691 3 and and CC cord-014597-66vd2mdu 1691 4 CHO CHO NNP cord-014597-66vd2mdu 1691 5 cells cell NNS cord-014597-66vd2mdu 1691 6 were be VBD cord-014597-66vd2mdu 1691 7 seeded seed VBN cord-014597-66vd2mdu 1691 8 at at IN cord-014597-66vd2mdu 1691 9 1×10 1×10 CD cord-014597-66vd2mdu 1691 10 6 6 CD cord-014597-66vd2mdu 1691 11 cells cell NNS cord-014597-66vd2mdu 1691 12 / / SYM cord-014597-66vd2mdu 1691 13 mL ml NN cord-014597-66vd2mdu 1691 14 in in IN cord-014597-66vd2mdu 1691 15 serum serum NN cord-014597-66vd2mdu 1691 16 free free JJ cord-014597-66vd2mdu 1691 17 medium medium NN cord-014597-66vd2mdu 1691 18 and and CC cord-014597-66vd2mdu 1691 19 transfected transfecte VBN cord-014597-66vd2mdu 1691 20 with with IN cord-014597-66vd2mdu 1691 21 PEIpro PEIpro NNP cord-014597-66vd2mdu 1691 22 ® ® NNPS cord-014597-66vd2mdu 1691 23 , , , cord-014597-66vd2mdu 1691 24 PEI PEI NNP cord-014597-66vd2mdu 1691 25 " " `` cord-014597-66vd2mdu 1691 26 Max Max NNP cord-014597-66vd2mdu 1691 27 " " '' cord-014597-66vd2mdu 1691 28 and and CC cord-014597-66vd2mdu 1691 29 L L NNP cord-014597-66vd2mdu 1691 30 - - HYPH cord-014597-66vd2mdu 1691 31 PEI PEI NNP cord-014597-66vd2mdu 1691 32 25 25 CD cord-014597-66vd2mdu 1691 33 kDa kDa NNS cord-014597-66vd2mdu 1692 1 ( ( -LRB- cord-014597-66vd2mdu 1692 2 Polysciences Polysciences NNP cord-014597-66vd2mdu 1692 3 , , , cord-014597-66vd2mdu 1692 4 Warrington Warrington NNP cord-014597-66vd2mdu 1692 5 , , , cord-014597-66vd2mdu 1692 6 PA PA NNP cord-014597-66vd2mdu 1692 7 ) ) -RRB- cord-014597-66vd2mdu 1692 8 resuspended resuspend VBD cord-014597-66vd2mdu 1692 9 at at IN cord-014597-66vd2mdu 1692 10 1 1 CD cord-014597-66vd2mdu 1692 11 mg mg NNP cord-014597-66vd2mdu 1692 12 / / SYM cord-014597-66vd2mdu 1692 13 ml ml NN cord-014597-66vd2mdu 1692 14 . . . cord-014597-66vd2mdu 1693 1 Luciferase Luciferase NNP cord-014597-66vd2mdu 1693 2 expression expression NN cord-014597-66vd2mdu 1693 3 was be VBD cord-014597-66vd2mdu 1693 4 assayed assay VBN cord-014597-66vd2mdu 1693 5 48 48 CD cord-014597-66vd2mdu 1693 6 h h NN cord-014597-66vd2mdu 1693 7 after after IN cord-014597-66vd2mdu 1693 8 transfection transfection NN cord-014597-66vd2mdu 1693 9 using use VBG cord-014597-66vd2mdu 1693 10 a a DT cord-014597-66vd2mdu 1693 11 conventional conventional JJ cord-014597-66vd2mdu 1693 12 luciferase luciferase NN cord-014597-66vd2mdu 1693 13 assay assay NN cord-014597-66vd2mdu 1693 14 Fig Fig NNP cord-014597-66vd2mdu 1693 15 . . . cord-014597-66vd2mdu 1693 16 2 2 LS cord-014597-66vd2mdu 1693 17 ( ( -LRB- cord-014597-66vd2mdu 1693 18 abstract abstract JJ cord-014597-66vd2mdu 1693 19 P-274 p-274 NN cord-014597-66vd2mdu 1693 20 ) ) -RRB- cord-014597-66vd2mdu 1693 21 . . . cord-014597-66vd2mdu 1694 1 PEIpro PEIpro NNP cord-014597-66vd2mdu 1695 1 ® ® NNP cord-014597-66vd2mdu 1695 2 is be VBZ cord-014597-66vd2mdu 1695 3 optimized optimize VBN cord-014597-66vd2mdu 1695 4 for for IN cord-014597-66vd2mdu 1695 5 transfection transfection NN cord-014597-66vd2mdu 1695 6 of of IN cord-014597-66vd2mdu 1695 7 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1695 8 and and CC cord-014597-66vd2mdu 1695 9 CHO CHO NNP cord-014597-66vd2mdu 1695 10 cells cell NNS cord-014597-66vd2mdu 1695 11 in in IN cord-014597-66vd2mdu 1695 12 several several JJ cord-014597-66vd2mdu 1695 13 specific specific JJ cord-014597-66vd2mdu 1695 14 synthetic synthetic JJ cord-014597-66vd2mdu 1695 15 culture culture NN cord-014597-66vd2mdu 1695 16 media medium NNS cord-014597-66vd2mdu 1695 17 . . . cord-014597-66vd2mdu 1696 1 Suspension suspension NN cord-014597-66vd2mdu 1696 2 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1696 3 and and CC cord-014597-66vd2mdu 1696 4 CHO CHO NNP cord-014597-66vd2mdu 1696 5 cells cell NNS cord-014597-66vd2mdu 1696 6 were be VBD cord-014597-66vd2mdu 1696 7 seeded seed VBN cord-014597-66vd2mdu 1696 8 following follow VBG cord-014597-66vd2mdu 1696 9 the the DT cord-014597-66vd2mdu 1696 10 recommended recommend VBN cord-014597-66vd2mdu 1696 11 protocol protocol NN cord-014597-66vd2mdu 1696 12 in in IN cord-014597-66vd2mdu 1696 13 serum serum NN cord-014597-66vd2mdu 1696 14 - - HYPH cord-014597-66vd2mdu 1696 15 free free JJ cord-014597-66vd2mdu 1696 16 media medium NNS cord-014597-66vd2mdu 1696 17 and and CC cord-014597-66vd2mdu 1696 18 transfected transfecte VBN cord-014597-66vd2mdu 1696 19 with with IN cord-014597-66vd2mdu 1696 20 PEIpro PEIpro NNP cord-014597-66vd2mdu 1697 1 ® ® VB cord-014597-66vd2mdu 1697 2 using use VBG cord-014597-66vd2mdu 1697 3 the the DT cord-014597-66vd2mdu 1697 4 standard standard JJ cord-014597-66vd2mdu 1697 5 conditions condition NNS cord-014597-66vd2mdu 1697 6 . . . cord-014597-66vd2mdu 1698 1 IgG3-Fc IgG3-Fc NNP cord-014597-66vd2mdu 1699 1 production production NN cord-014597-66vd2mdu 1699 2 was be VBD cord-014597-66vd2mdu 1699 3 assayed assay VBN cord-014597-66vd2mdu 1699 4 48 48 CD cord-014597-66vd2mdu 1699 5 h h NN cord-014597-66vd2mdu 1699 6 after after IN cord-014597-66vd2mdu 1699 7 transfection transfection NN cord-014597-66vd2mdu 1699 8 using use VBG cord-014597-66vd2mdu 1699 9 protein protein NN cord-014597-66vd2mdu 1699 10 G g NN cord-014597-66vd2mdu 1699 11 affinity affinity NN cord-014597-66vd2mdu 1699 12 quantification quantification NN cord-014597-66vd2mdu 1699 13 ( ( -LRB- cord-014597-66vd2mdu 1699 14 HPLC HPLC NNP cord-014597-66vd2mdu 1699 15 ) ) -RRB- cord-014597-66vd2mdu 1699 16 Monoclonal monoclonal JJ cord-014597-66vd2mdu 1699 17 antibodies antibody NNS cord-014597-66vd2mdu 1699 18 ( ( -LRB- cord-014597-66vd2mdu 1699 19 MAbs MAbs NNP cord-014597-66vd2mdu 1699 20 ) ) -RRB- cord-014597-66vd2mdu 1699 21 , , , cord-014597-66vd2mdu 1699 22 which which WDT cord-014597-66vd2mdu 1699 23 are be VBP cord-014597-66vd2mdu 1699 24 widely widely RB cord-014597-66vd2mdu 1699 25 used use VBN cord-014597-66vd2mdu 1699 26 in in IN cord-014597-66vd2mdu 1699 27 anticancer anticancer JJ cord-014597-66vd2mdu 1699 28 therapies therapy NNS cord-014597-66vd2mdu 1699 29 , , , cord-014597-66vd2mdu 1699 30 are be VBP cord-014597-66vd2mdu 1699 31 mainly mainly RB cord-014597-66vd2mdu 1699 32 produced produce VBN cord-014597-66vd2mdu 1699 33 by by IN cord-014597-66vd2mdu 1699 34 mammalian mammalian JJ cord-014597-66vd2mdu 1699 35 cell cell NN cord-014597-66vd2mdu 1699 36 lines line NNS cord-014597-66vd2mdu 1699 37 . . . cord-014597-66vd2mdu 1700 1 MAb MAb NNS cord-014597-66vd2mdu 1700 2 conjugation conjugation NN cord-014597-66vd2mdu 1700 3 to to IN cord-014597-66vd2mdu 1700 4 biological biological JJ cord-014597-66vd2mdu 1700 5 molecules molecule NNS cord-014597-66vd2mdu 1700 6 for for IN cord-014597-66vd2mdu 1700 7 enhancing enhance VBG cord-014597-66vd2mdu 1700 8 their -PRON- PRP$ cord-014597-66vd2mdu 1700 9 antitumor antitumor JJ cord-014597-66vd2mdu 1700 10 activity activity NN cord-014597-66vd2mdu 1700 11 offers offer VBZ cord-014597-66vd2mdu 1700 12 a a DT cord-014597-66vd2mdu 1700 13 new new JJ cord-014597-66vd2mdu 1700 14 powerful powerful JJ cord-014597-66vd2mdu 1700 15 tool tool NN cord-014597-66vd2mdu 1700 16 for for IN cord-014597-66vd2mdu 1700 17 anticancer anticancer JJ cord-014597-66vd2mdu 1700 18 therapies therapy NNS cord-014597-66vd2mdu 1700 19 . . . cord-014597-66vd2mdu 1701 1 We -PRON- PRP cord-014597-66vd2mdu 1701 2 have have VBP cord-014597-66vd2mdu 1701 3 assessed assess VBN cord-014597-66vd2mdu 1701 4 the the DT cord-014597-66vd2mdu 1701 5 production production NN cord-014597-66vd2mdu 1701 6 of of IN cord-014597-66vd2mdu 1701 7 commercially commercially RB cord-014597-66vd2mdu 1701 8 approved approve VBN cord-014597-66vd2mdu 1701 9 anti anti JJ cord-014597-66vd2mdu 1701 10 - - JJ cord-014597-66vd2mdu 1701 11 HER2 her2 JJ cord-014597-66vd2mdu 1701 12 therapeutic therapeutic JJ cord-014597-66vd2mdu 1701 13 antibody antibody NN cord-014597-66vd2mdu 1701 14 Trastuzumab Trastuzumab NNP cord-014597-66vd2mdu 1701 15 ( ( -LRB- cord-014597-66vd2mdu 1701 16 Tzmb Tzmb NNP cord-014597-66vd2mdu 1701 17 ) ) -RRB- cord-014597-66vd2mdu 1701 18 [ [ -LRB- cord-014597-66vd2mdu 1701 19 1 1 CD cord-014597-66vd2mdu 1701 20 ] ] -RRB- cord-014597-66vd2mdu 1701 21 and and CC cord-014597-66vd2mdu 1701 22 also also RB cord-014597-66vd2mdu 1701 23 its -PRON- PRP$ cord-014597-66vd2mdu 1701 24 fusion fusion NN cord-014597-66vd2mdu 1701 25 with with IN cord-014597-66vd2mdu 1701 26 interferon interferon NN cord-014597-66vd2mdu 1701 27 - - HYPH cord-014597-66vd2mdu 1701 28 α2b α2b JJ cord-014597-66vd2mdu 1701 29 ( ( -LRB- cord-014597-66vd2mdu 1701 30 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1701 31 ) ) -RRB- cord-014597-66vd2mdu 1701 32 . . . cord-014597-66vd2mdu 1702 1 Two two CD cord-014597-66vd2mdu 1702 2 cloning clone VBG cord-014597-66vd2mdu 1702 3 strategies strategy NNS cord-014597-66vd2mdu 1702 4 consisting consist VBG cord-014597-66vd2mdu 1702 5 in in IN cord-014597-66vd2mdu 1702 6 transfecting transfecte VBG cord-014597-66vd2mdu 1702 7 CHO CHO NNP cord-014597-66vd2mdu 1702 8 - - HYPH cord-014597-66vd2mdu 1702 9 S S NNP cord-014597-66vd2mdu 1702 10 and and CC cord-014597-66vd2mdu 1702 11 HEK293 HEK293 NNP cord-014597-66vd2mdu 1702 12 cell cell NN cord-014597-66vd2mdu 1702 13 lines line NNS cord-014597-66vd2mdu 1702 14 with with IN cord-014597-66vd2mdu 1702 15 two two CD cord-014597-66vd2mdu 1702 16 bicistronic bicistronic JJ cord-014597-66vd2mdu 1702 17 or or CC cord-014597-66vd2mdu 1702 18 with with IN cord-014597-66vd2mdu 1702 19 a a DT cord-014597-66vd2mdu 1702 20 single single JJ cord-014597-66vd2mdu 1702 21 tricistronic tricistronic JJ cord-014597-66vd2mdu 1702 22 plasmids plasmid NNS cord-014597-66vd2mdu 1702 23 have have VBP cord-014597-66vd2mdu 1702 24 been be VBN cord-014597-66vd2mdu 1702 25 assessed assess VBN cord-014597-66vd2mdu 1702 26 . . . cord-014597-66vd2mdu 1703 1 The the DT cord-014597-66vd2mdu 1703 2 in in FW cord-014597-66vd2mdu 1703 3 vitro vitro FW cord-014597-66vd2mdu 1703 4 efficacy efficacy NN cord-014597-66vd2mdu 1703 5 of of IN cord-014597-66vd2mdu 1703 6 both both DT cord-014597-66vd2mdu 1703 7 antibodies antibody NNS cord-014597-66vd2mdu 1703 8 has have VBZ cord-014597-66vd2mdu 1703 9 been be VBN cord-014597-66vd2mdu 1703 10 tested test VBN cord-014597-66vd2mdu 1703 11 and and CC cord-014597-66vd2mdu 1703 12 compared compare VBN cord-014597-66vd2mdu 1703 13 side side NN cord-014597-66vd2mdu 1703 14 by by IN cord-014597-66vd2mdu 1703 15 side side NN cord-014597-66vd2mdu 1703 16 . . . cord-014597-66vd2mdu 1704 1 Tzmb Tzmb NNP cord-014597-66vd2mdu 1704 2 heavy heavy JJ cord-014597-66vd2mdu 1704 3 and and CC cord-014597-66vd2mdu 1704 4 light light JJ cord-014597-66vd2mdu 1704 5 chains chain NNS cord-014597-66vd2mdu 1704 6 were be VBD cord-014597-66vd2mdu 1704 7 cloned clone VBN cord-014597-66vd2mdu 1704 8 in in IN cord-014597-66vd2mdu 1704 9 two two CD cord-014597-66vd2mdu 1704 10 bicistronic bicistronic JJ cord-014597-66vd2mdu 1704 11 plasmids plasmid NNS cord-014597-66vd2mdu 1704 12 ( ( -LRB- cord-014597-66vd2mdu 1704 13 pIRESpuro3 pIRESpuro3 NNPS cord-014597-66vd2mdu 1704 14 and and CC cord-014597-66vd2mdu 1704 15 pIRESneo3 pIRESneo3 NNP cord-014597-66vd2mdu 1704 16 , , , cord-014597-66vd2mdu 1704 17 Clontech Clontech NNP cord-014597-66vd2mdu 1704 18 ) ) -RRB- cord-014597-66vd2mdu 1704 19 and and CC cord-014597-66vd2mdu 1704 20 in in IN cord-014597-66vd2mdu 1704 21 a a DT cord-014597-66vd2mdu 1704 22 tricistronic tricistronic JJ cord-014597-66vd2mdu 1704 23 plasmid plasmid NN cord-014597-66vd2mdu 1704 24 derived derive VBN cord-014597-66vd2mdu 1704 25 from from IN cord-014597-66vd2mdu 1704 26 pIRESpuro3 pIRESpuro3 NNP cord-014597-66vd2mdu 1704 27 . . . cord-014597-66vd2mdu 1705 1 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1705 2 was be VBD cord-014597-66vd2mdu 1705 3 spliced splice VBN cord-014597-66vd2mdu 1705 4 to to IN cord-014597-66vd2mdu 1705 5 Tzmb Tzmb NNP cord-014597-66vd2mdu 1705 6 heavy heavy JJ cord-014597-66vd2mdu 1705 7 chain chain NN cord-014597-66vd2mdu 1705 8 by by IN cord-014597-66vd2mdu 1705 9 overlap overlap NN cord-014597-66vd2mdu 1705 10 extension extension NN cord-014597-66vd2mdu 1705 11 PCR PCR NNP cord-014597-66vd2mdu 1705 12 and and CC cord-014597-66vd2mdu 1705 13 the the DT cord-014597-66vd2mdu 1705 14 resulting result VBG cord-014597-66vd2mdu 1705 15 Tzmb Tzmb NNP cord-014597-66vd2mdu 1705 16 - - HYPH cord-014597-66vd2mdu 1705 17 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1705 18 fusion fusion NN cord-014597-66vd2mdu 1705 19 protein protein NN cord-014597-66vd2mdu 1705 20 was be VBD cord-014597-66vd2mdu 1705 21 also also RB cord-014597-66vd2mdu 1705 22 cloned clone VBN cord-014597-66vd2mdu 1705 23 in in IN cord-014597-66vd2mdu 1705 24 the the DT cord-014597-66vd2mdu 1705 25 expression expression NN cord-014597-66vd2mdu 1705 26 vectors vector NNS cord-014597-66vd2mdu 1705 27 in in IN cord-014597-66vd2mdu 1705 28 the the DT cord-014597-66vd2mdu 1705 29 same same JJ cord-014597-66vd2mdu 1705 30 way way NN cord-014597-66vd2mdu 1705 31 than than IN cord-014597-66vd2mdu 1705 32 non non JJ cord-014597-66vd2mdu 1705 33 - - JJ cord-014597-66vd2mdu 1705 34 modified modified JJ cord-014597-66vd2mdu 1705 35 Tzmb Tzmb NNP cord-014597-66vd2mdu 1705 36 . . . cord-014597-66vd2mdu 1706 1 Selected select VBN cord-014597-66vd2mdu 1706 2 cell cell NN cord-014597-66vd2mdu 1706 3 pools pool NNS cord-014597-66vd2mdu 1706 4 were be VBD cord-014597-66vd2mdu 1706 5 cultured culture VBN cord-014597-66vd2mdu 1706 6 in in IN cord-014597-66vd2mdu 1706 7 125 125 CD cord-014597-66vd2mdu 1706 8 ml ml NN cord-014597-66vd2mdu 1706 9 shake shake NN cord-014597-66vd2mdu 1706 10 flasks flask NNS cord-014597-66vd2mdu 1706 11 containing contain VBG cord-014597-66vd2mdu 1706 12 SFMTransfx sfmtransfx NN cord-014597-66vd2mdu 1706 13 supplemented supplement VBN cord-014597-66vd2mdu 1706 14 with with IN cord-014597-66vd2mdu 1706 15 10 10 CD cord-014597-66vd2mdu 1706 16 % % NN cord-014597-66vd2mdu 1706 17 v v NN cord-014597-66vd2mdu 1706 18 / / SYM cord-014597-66vd2mdu 1706 19 v v NN cord-014597-66vd2mdu 1706 20 of of IN cord-014597-66vd2mdu 1706 21 Cell Cell NNP cord-014597-66vd2mdu 1706 22 Boost Boost NNP cord-014597-66vd2mdu 1706 23 5 5 CD cord-014597-66vd2mdu 1706 24 ( ( -LRB- cord-014597-66vd2mdu 1706 25 HyClone HyClone NNP cord-014597-66vd2mdu 1706 26 ) ) -RRB- cord-014597-66vd2mdu 1706 27 , , , cord-014597-66vd2mdu 1706 28 4 4 CD cord-014597-66vd2mdu 1706 29 mM mm CD cord-014597-66vd2mdu 1706 30 of of IN cord-014597-66vd2mdu 1706 31 GlutaMAX GlutaMAX NNP cord-014597-66vd2mdu 1707 1 ( ( -LRB- cord-014597-66vd2mdu 1707 2 Gibco Gibco NNP cord-014597-66vd2mdu 1707 3 ) ) -RRB- cord-014597-66vd2mdu 1707 4 and and CC cord-014597-66vd2mdu 1707 5 2 2 CD cord-014597-66vd2mdu 1707 6 μg μg NN cord-014597-66vd2mdu 1707 7 / / SYM cord-014597-66vd2mdu 1707 8 ml ml NNS cord-014597-66vd2mdu 1707 9 of of IN cord-014597-66vd2mdu 1707 10 puromycin puromycin NNS cord-014597-66vd2mdu 1707 11 and and CC cord-014597-66vd2mdu 1707 12 also also RB cord-014597-66vd2mdu 1707 13 with with IN cord-014597-66vd2mdu 1707 14 700 700 CD cord-014597-66vd2mdu 1707 15 μg μg NNP cord-014597-66vd2mdu 1707 16 / / SYM cord-014597-66vd2mdu 1707 17 ml ml CC cord-014597-66vd2mdu 1707 18 neomycin neomycin NN cord-014597-66vd2mdu 1707 19 in in IN cord-014597-66vd2mdu 1707 20 the the DT cord-014597-66vd2mdu 1707 21 case case NN cord-014597-66vd2mdu 1707 22 of of IN cord-014597-66vd2mdu 1707 23 the the DT cord-014597-66vd2mdu 1707 24 cells cell NNS cord-014597-66vd2mdu 1707 25 transfected transfecte VBN cord-014597-66vd2mdu 1707 26 with with IN cord-014597-66vd2mdu 1707 27 pIRES pIRES NNP cord-014597-66vd2mdu 1707 28 - - HYPH cord-014597-66vd2mdu 1707 29 neo3 neo3 NNP cord-014597-66vd2mdu 1707 30 . . . cord-014597-66vd2mdu 1708 1 Cells cell NNS cord-014597-66vd2mdu 1708 2 were be VBD cord-014597-66vd2mdu 1708 3 cultivated cultivate VBN cord-014597-66vd2mdu 1708 4 in in IN cord-014597-66vd2mdu 1708 5 the the DT cord-014597-66vd2mdu 1708 6 same same JJ cord-014597-66vd2mdu 1708 7 conditions condition NNS cord-014597-66vd2mdu 1708 8 as as IN cord-014597-66vd2mdu 1708 9 described describe VBN cord-014597-66vd2mdu 1708 10 elsewhere elsewhere RB cord-014597-66vd2mdu 1708 11 [ [ -LRB- cord-014597-66vd2mdu 1708 12 2 2 CD cord-014597-66vd2mdu 1708 13 ] ] -RRB- cord-014597-66vd2mdu 1708 14 . . . cord-014597-66vd2mdu 1709 1 Purified purify VBN cord-014597-66vd2mdu 1709 2 products product NNS cord-014597-66vd2mdu 1709 3 ( ( -LRB- cord-014597-66vd2mdu 1709 4 using use VBG cord-014597-66vd2mdu 1709 5 protein protein NN cord-014597-66vd2mdu 1709 6 A a DT cord-014597-66vd2mdu 1709 7 chromatography chromatography NN cord-014597-66vd2mdu 1709 8 ( ( -LRB- cord-014597-66vd2mdu 1709 9 HiTrap HiTrap NNP cord-014597-66vd2mdu 1709 10 MabSelect MabSelect NNP cord-014597-66vd2mdu 1710 1 Sure sure UH cord-014597-66vd2mdu 1710 2 , , , cord-014597-66vd2mdu 1710 3 ÄKTA ÄKTA NNP cord-014597-66vd2mdu 1710 4 Avant Avant NNP cord-014597-66vd2mdu 1710 5 150 150 CD cord-014597-66vd2mdu 1710 6 ) ) -RRB- cord-014597-66vd2mdu 1710 7 ) ) -RRB- cord-014597-66vd2mdu 1710 8 were be VBD cord-014597-66vd2mdu 1710 9 quantified quantify VBN cord-014597-66vd2mdu 1710 10 by by IN cord-014597-66vd2mdu 1710 11 both both CC cord-014597-66vd2mdu 1710 12 ELISA ELISA NNP cord-014597-66vd2mdu 1710 13 and and CC cord-014597-66vd2mdu 1710 14 SDS SDS NNP cord-014597-66vd2mdu 1710 15 - - HYPH cord-014597-66vd2mdu 1710 16 PAGE PAGE NNP cord-014597-66vd2mdu 1710 17 . . . cord-014597-66vd2mdu 1711 1 Antigen antigen NN cord-014597-66vd2mdu 1711 2 binding binding JJ cord-014597-66vd2mdu 1711 3 test test NN cord-014597-66vd2mdu 1711 4 was be VBD cord-014597-66vd2mdu 1711 5 performed perform VBN cord-014597-66vd2mdu 1711 6 in in IN cord-014597-66vd2mdu 1711 7 Sk Sk NNP cord-014597-66vd2mdu 1711 8 - - HYPH cord-014597-66vd2mdu 1711 9 br-3 br-3 NNP cord-014597-66vd2mdu 1711 10 breast breast NN cord-014597-66vd2mdu 1711 11 cancer cancer NN cord-014597-66vd2mdu 1711 12 cell cell NN cord-014597-66vd2mdu 1711 13 line line NN cord-014597-66vd2mdu 1711 14 by by IN cord-014597-66vd2mdu 1711 15 means mean NNS cord-014597-66vd2mdu 1711 16 of of IN cord-014597-66vd2mdu 1711 17 flow flow NN cord-014597-66vd2mdu 1711 18 cytometry cytometry NN cord-014597-66vd2mdu 1711 19 analysis analysis NN cord-014597-66vd2mdu 1711 20 . . . cord-014597-66vd2mdu 1712 1 The the DT cord-014597-66vd2mdu 1712 2 biological biological JJ cord-014597-66vd2mdu 1712 3 activity activity NN cord-014597-66vd2mdu 1712 4 of of IN cord-014597-66vd2mdu 1712 5 the the DT cord-014597-66vd2mdu 1712 6 different different JJ cord-014597-66vd2mdu 1712 7 candidates candidate NNS cord-014597-66vd2mdu 1712 8 was be VBD cord-014597-66vd2mdu 1712 9 tested test VBN cord-014597-66vd2mdu 1712 10 with with IN cord-014597-66vd2mdu 1712 11 MTT MTT NNP cord-014597-66vd2mdu 1712 12 assay assay NN cord-014597-66vd2mdu 1712 13 . . . cord-014597-66vd2mdu 1713 1 Both both CC cord-014597-66vd2mdu 1713 2 Tzmb Tzmb NNP cord-014597-66vd2mdu 1713 3 and and CC cord-014597-66vd2mdu 1713 4 the the DT cord-014597-66vd2mdu 1713 5 fusion fusion NN cord-014597-66vd2mdu 1713 6 protein protein NN cord-014597-66vd2mdu 1713 7 Tzmb Tzmb NNP cord-014597-66vd2mdu 1713 8 - - HYPH cord-014597-66vd2mdu 1713 9 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1713 10 have have VBP cord-014597-66vd2mdu 1713 11 been be VBN cord-014597-66vd2mdu 1713 12 successfully successfully RB cord-014597-66vd2mdu 1713 13 expressed express VBN cord-014597-66vd2mdu 1713 14 in in IN cord-014597-66vd2mdu 1713 15 CHO CHO NNP cord-014597-66vd2mdu 1713 16 - - HYPH cord-014597-66vd2mdu 1713 17 S S NNP cord-014597-66vd2mdu 1713 18 and and CC cord-014597-66vd2mdu 1713 19 HEK293 HEK293 NNP cord-014597-66vd2mdu 1713 20 , , , cord-014597-66vd2mdu 1713 21 which which WDT cord-014597-66vd2mdu 1713 22 use use VBP cord-014597-66vd2mdu 1713 23 for for IN cord-014597-66vd2mdu 1713 24 heterologous heterologous JJ cord-014597-66vd2mdu 1713 25 protein protein NN cord-014597-66vd2mdu 1713 26 expression expression NN cord-014597-66vd2mdu 1713 27 have have VBP cord-014597-66vd2mdu 1713 28 previously previously RB cord-014597-66vd2mdu 1713 29 been be VBN cord-014597-66vd2mdu 1713 30 optimized optimize VBN cord-014597-66vd2mdu 1713 31 in in IN cord-014597-66vd2mdu 1713 32 prior prior JJ cord-014597-66vd2mdu 1713 33 works work NNS cord-014597-66vd2mdu 1713 34 [ [ -LRB- cord-014597-66vd2mdu 1713 35 3 3 CD cord-014597-66vd2mdu 1713 36 ] ] -RRB- cord-014597-66vd2mdu 1713 37 . . . cord-014597-66vd2mdu 1714 1 The the DT cord-014597-66vd2mdu 1714 2 tricistronic tricistronic JJ cord-014597-66vd2mdu 1714 3 strategy strategy NN cord-014597-66vd2mdu 1714 4 resulted result VBD cord-014597-66vd2mdu 1714 5 in in IN cord-014597-66vd2mdu 1714 6 the the DT cord-014597-66vd2mdu 1714 7 most most RBS cord-014597-66vd2mdu 1714 8 efficient efficient JJ cord-014597-66vd2mdu 1714 9 , , , cord-014597-66vd2mdu 1714 10 showing show VBG cord-014597-66vd2mdu 1714 11 a a DT cord-014597-66vd2mdu 1714 12 3.5fold 3.5fold CD cord-014597-66vd2mdu 1714 13 increase increase NN cord-014597-66vd2mdu 1714 14 in in IN cord-014597-66vd2mdu 1714 15 terms term NNS cord-014597-66vd2mdu 1714 16 of of IN cord-014597-66vd2mdu 1714 17 productivity productivity NN cord-014597-66vd2mdu 1714 18 with with IN cord-014597-66vd2mdu 1714 19 respect respect NN cord-014597-66vd2mdu 1714 20 to to IN cord-014597-66vd2mdu 1714 21 the the DT cord-014597-66vd2mdu 1714 22 bicistronic bicistronic JJ cord-014597-66vd2mdu 1714 23 double double JJ cord-014597-66vd2mdu 1714 24 - - HYPH cord-014597-66vd2mdu 1714 25 transfection transfection NN cord-014597-66vd2mdu 1714 26 for for IN cord-014597-66vd2mdu 1714 27 Tzmb Tzmb NNP cord-014597-66vd2mdu 1714 28 in in IN cord-014597-66vd2mdu 1714 29 CHO CHO NNP cord-014597-66vd2mdu 1714 30 - - HYPH cord-014597-66vd2mdu 1714 31 S S NNP cord-014597-66vd2mdu 1714 32 cells cell NNS cord-014597-66vd2mdu 1714 33 and and CC cord-014597-66vd2mdu 1714 34 a a DT cord-014597-66vd2mdu 1714 35 5-fold 5-fold CD cord-014597-66vd2mdu 1714 36 increase increase NN cord-014597-66vd2mdu 1714 37 in in IN cord-014597-66vd2mdu 1714 38 HEK293 HEK293 NNP cord-014597-66vd2mdu 1714 39 cells cell NNS cord-014597-66vd2mdu 1714 40 ( ( -LRB- cord-014597-66vd2mdu 1714 41 Fig fig NN cord-014597-66vd2mdu 1714 42 . . . cord-014597-66vd2mdu 1714 43 1a 1a CD cord-014597-66vd2mdu 1714 44 ) ) -RRB- cord-014597-66vd2mdu 1714 45 . . . cord-014597-66vd2mdu 1715 1 In in IN cord-014597-66vd2mdu 1715 2 the the DT cord-014597-66vd2mdu 1715 3 case case NN cord-014597-66vd2mdu 1715 4 of of IN cord-014597-66vd2mdu 1715 5 Tzmb Tzmb NNP cord-014597-66vd2mdu 1715 6 - - HYPH cord-014597-66vd2mdu 1715 7 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1715 8 , , , cord-014597-66vd2mdu 1715 9 the the DT cord-014597-66vd2mdu 1715 10 tricistronic tricistronic NNP cord-014597-66vd2mdu 1715 11 strategy strategy NN cord-014597-66vd2mdu 1715 12 also also RB cord-014597-66vd2mdu 1715 13 allowed allow VBD cord-014597-66vd2mdu 1715 14 to to TO cord-014597-66vd2mdu 1715 15 achieve achieve VB cord-014597-66vd2mdu 1715 16 higher high JJR cord-014597-66vd2mdu 1715 17 productivities productivity NNS cord-014597-66vd2mdu 1715 18 than than IN cord-014597-66vd2mdu 1715 19 the the DT cord-014597-66vd2mdu 1715 20 bicistronic bicistronic JJ cord-014597-66vd2mdu 1715 21 one one CD cord-014597-66vd2mdu 1715 22 ( ( -LRB- cord-014597-66vd2mdu 1715 23 Fig Fig NNP cord-014597-66vd2mdu 1715 24 . . . cord-014597-66vd2mdu 1715 25 1b 1b CD cord-014597-66vd2mdu 1715 26 ) ) -RRB- cord-014597-66vd2mdu 1715 27 . . . cord-014597-66vd2mdu 1716 1 Regarding regard VBG cord-014597-66vd2mdu 1716 2 the the DT cord-014597-66vd2mdu 1716 3 differences difference NNS cord-014597-66vd2mdu 1716 4 of of IN cord-014597-66vd2mdu 1716 5 specific specific JJ cord-014597-66vd2mdu 1716 6 productivity productivity NN cord-014597-66vd2mdu 1716 7 between between IN cord-014597-66vd2mdu 1716 8 both both DT cord-014597-66vd2mdu 1716 9 cell cell NN cord-014597-66vd2mdu 1716 10 lines line NNS cord-014597-66vd2mdu 1716 11 tested test VBN cord-014597-66vd2mdu 1716 12 , , , cord-014597-66vd2mdu 1716 13 HEK293 HEK293 NNP cord-014597-66vd2mdu 1716 14 emerged emerge VBD cord-014597-66vd2mdu 1716 15 as as IN cord-014597-66vd2mdu 1716 16 the the DT cord-014597-66vd2mdu 1716 17 best good JJS cord-014597-66vd2mdu 1716 18 production production NN cord-014597-66vd2mdu 1716 19 host host NN cord-014597-66vd2mdu 1716 20 candidate candidate NN cord-014597-66vd2mdu 1716 21 , , , cord-014597-66vd2mdu 1716 22 for for IN cord-014597-66vd2mdu 1716 23 the the DT cord-014597-66vd2mdu 1716 24 two two CD cord-014597-66vd2mdu 1716 25 tested test VBN cord-014597-66vd2mdu 1716 26 strategies strategy NNS cord-014597-66vd2mdu 1716 27 ( ( -LRB- cord-014597-66vd2mdu 1716 28 tricistronic tricistronic NNP cord-014597-66vd2mdu 1716 29 and and CC cord-014597-66vd2mdu 1716 30 bicistronic bicistronic NNP cord-014597-66vd2mdu 1716 31 ) ) -RRB- cord-014597-66vd2mdu 1716 32 and and CC cord-014597-66vd2mdu 1716 33 for for IN cord-014597-66vd2mdu 1716 34 the the DT cord-014597-66vd2mdu 1716 35 two two CD cord-014597-66vd2mdu 1716 36 produced produce VBN cord-014597-66vd2mdu 1716 37 proteins protein NNS cord-014597-66vd2mdu 1716 38 , , , cord-014597-66vd2mdu 1716 39 showing show VBG cord-014597-66vd2mdu 1716 40 a a DT cord-014597-66vd2mdu 1716 41 1.5-fold 1.5-fold CD cord-014597-66vd2mdu 1716 42 increase increase NN cord-014597-66vd2mdu 1716 43 in in IN cord-014597-66vd2mdu 1716 44 terms term NNS cord-014597-66vd2mdu 1716 45 of of IN cord-014597-66vd2mdu 1716 46 productivity productivity NN cord-014597-66vd2mdu 1716 47 with with IN cord-014597-66vd2mdu 1716 48 respect respect NN cord-014597-66vd2mdu 1716 49 to to IN cord-014597-66vd2mdu 1716 50 CHO CHO NNP cord-014597-66vd2mdu 1716 51 - - HYPH cord-014597-66vd2mdu 1716 52 S S NNP cord-014597-66vd2mdu 1716 53 cells cell NNS cord-014597-66vd2mdu 1716 54 for for IN cord-014597-66vd2mdu 1716 55 Tzmb Tzmb NNP cord-014597-66vd2mdu 1716 56 using use VBG cord-014597-66vd2mdu 1716 57 the the DT cord-014597-66vd2mdu 1716 58 tricistronic tricistronic NNP cord-014597-66vd2mdu 1716 59 strategy strategy NN cord-014597-66vd2mdu 1716 60 . . . cord-014597-66vd2mdu 1717 1 Tzmb Tzmb NNP cord-014597-66vd2mdu 1717 2 and and CC cord-014597-66vd2mdu 1717 3 Tzmb Tzmb NNP cord-014597-66vd2mdu 1717 4 - - HYPH cord-014597-66vd2mdu 1717 5 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1717 6 were be VBD cord-014597-66vd2mdu 1717 7 analysed analyse VBN cord-014597-66vd2mdu 1717 8 in in IN cord-014597-66vd2mdu 1717 9 terms term NNS cord-014597-66vd2mdu 1717 10 of of IN cord-014597-66vd2mdu 1717 11 their -PRON- PRP$ cord-014597-66vd2mdu 1717 12 antigen antigen NN cord-014597-66vd2mdu 1717 13 binding bind VBG cord-014597-66vd2mdu 1717 14 capacity capacity NN cord-014597-66vd2mdu 1717 15 , , , cord-014597-66vd2mdu 1717 16 and and CC cord-014597-66vd2mdu 1717 17 both both DT cord-014597-66vd2mdu 1717 18 were be VBD cord-014597-66vd2mdu 1717 19 find find JJ cord-014597-66vd2mdu 1717 20 to to TO cord-014597-66vd2mdu 1717 21 efficiently efficiently RB cord-014597-66vd2mdu 1717 22 bind bind VB cord-014597-66vd2mdu 1717 23 to to IN cord-014597-66vd2mdu 1717 24 HER2 HER2 NNP cord-014597-66vd2mdu 1717 25 + + CC cord-014597-66vd2mdu 1718 1 Skbr-3 skbr-3 JJ cord-014597-66vd2mdu 1718 2 cells cell NNS cord-014597-66vd2mdu 1718 3 ( ( -LRB- cord-014597-66vd2mdu 1718 4 Fig Fig NNP cord-014597-66vd2mdu 1718 5 . . . cord-014597-66vd2mdu 1718 6 1c 1c CD cord-014597-66vd2mdu 1718 7 ) ) -RRB- cord-014597-66vd2mdu 1718 8 . . . cord-014597-66vd2mdu 1719 1 Thus thus RB cord-014597-66vd2mdu 1719 2 , , , cord-014597-66vd2mdu 1719 3 the the DT cord-014597-66vd2mdu 1719 4 antibody antibody NN cord-014597-66vd2mdu 1719 5 affinity affinity NN cord-014597-66vd2mdu 1719 6 to to IN cord-014597-66vd2mdu 1719 7 HER2 HER2 NNP cord-014597-66vd2mdu 1719 8 antigen antigen NN cord-014597-66vd2mdu 1719 9 has have VBZ cord-014597-66vd2mdu 1719 10 not not RB cord-014597-66vd2mdu 1719 11 been be VBN cord-014597-66vd2mdu 1719 12 affected affect VBN cord-014597-66vd2mdu 1719 13 when when WRB cord-014597-66vd2mdu 1719 14 fused fuse VBN cord-014597-66vd2mdu 1719 15 to to IN cord-014597-66vd2mdu 1719 16 INF INF NNP cord-014597-66vd2mdu 1719 17 - - HYPH cord-014597-66vd2mdu 1719 18 α2b α2b JJ cord-014597-66vd2mdu 1719 19 . . . cord-014597-66vd2mdu 1720 1 Finally finally RB cord-014597-66vd2mdu 1720 2 , , , cord-014597-66vd2mdu 1720 3 antiproliferative antiproliferative JJ cord-014597-66vd2mdu 1720 4 activity activity NN cord-014597-66vd2mdu 1720 5 of of IN cord-014597-66vd2mdu 1720 6 Tzmb Tzmb NNP cord-014597-66vd2mdu 1720 7 and and CC cord-014597-66vd2mdu 1720 8 Tzmb Tzmb NNP cord-014597-66vd2mdu 1720 9 - - HYPH cord-014597-66vd2mdu 1720 10 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1720 11 were be VBD cord-014597-66vd2mdu 1720 12 assessed assess VBN cord-014597-66vd2mdu 1720 13 on on IN cord-014597-66vd2mdu 1720 14 the the DT cord-014597-66vd2mdu 1720 15 same same JJ cord-014597-66vd2mdu 1720 16 Sk Sk NNP cord-014597-66vd2mdu 1720 17 - - HYPH cord-014597-66vd2mdu 1720 18 br-3 br-3 NNP cord-014597-66vd2mdu 1720 19 cells cell NNS cord-014597-66vd2mdu 1720 20 . . . cord-014597-66vd2mdu 1721 1 At at IN cord-014597-66vd2mdu 1721 2 a a DT cord-014597-66vd2mdu 1721 3 concentration concentration NN cord-014597-66vd2mdu 1721 4 of of IN cord-014597-66vd2mdu 1721 5 500 500 CD cord-014597-66vd2mdu 1721 6 nM nm CD cord-014597-66vd2mdu 1721 7 of of IN cord-014597-66vd2mdu 1721 8 Tzmb Tzmb NNP cord-014597-66vd2mdu 1721 9 , , , cord-014597-66vd2mdu 1721 10 and and CC cord-014597-66vd2mdu 1721 11 after after IN cord-014597-66vd2mdu 1721 12 a a DT cord-014597-66vd2mdu 1721 13 72-hour 72-hour CD cord-014597-66vd2mdu 1721 14 incubation incubation NN cord-014597-66vd2mdu 1721 15 , , , cord-014597-66vd2mdu 1721 16 Sk Sk NNP cord-014597-66vd2mdu 1721 17 - - HYPH cord-014597-66vd2mdu 1721 18 br-3 br-3 NNP cord-014597-66vd2mdu 1721 19 cells cell NNS cord-014597-66vd2mdu 1721 20 presented present VBD cord-014597-66vd2mdu 1721 21 a a DT cord-014597-66vd2mdu 1721 22 83 83 CD cord-014597-66vd2mdu 1721 23 % % NN cord-014597-66vd2mdu 1721 24 growth growth NN cord-014597-66vd2mdu 1721 25 with with IN cord-014597-66vd2mdu 1721 26 respect respect NN cord-014597-66vd2mdu 1721 27 to to IN cord-014597-66vd2mdu 1721 28 the the DT cord-014597-66vd2mdu 1721 29 untreated untreated JJ cord-014597-66vd2mdu 1721 30 control control NN cord-014597-66vd2mdu 1721 31 . . . cord-014597-66vd2mdu 1722 1 However however RB cord-014597-66vd2mdu 1722 2 , , , cord-014597-66vd2mdu 1722 3 no no DT cord-014597-66vd2mdu 1722 4 antiproliferative antiproliferative JJ cord-014597-66vd2mdu 1722 5 effect effect NN cord-014597-66vd2mdu 1722 6 was be VBD cord-014597-66vd2mdu 1722 7 observed observe VBN cord-014597-66vd2mdu 1722 8 for for IN cord-014597-66vd2mdu 1722 9 Tzmb Tzmb NNP cord-014597-66vd2mdu 1722 10 - - HYPH cord-014597-66vd2mdu 1722 11 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1723 1 ( ( -LRB- cord-014597-66vd2mdu 1723 2 Fig Fig NNP cord-014597-66vd2mdu 1723 3 . . . cord-014597-66vd2mdu 1723 4 1d 1d CD cord-014597-66vd2mdu 1723 5 ) ) -RRB- cord-014597-66vd2mdu 1723 6 . . . cord-014597-66vd2mdu 1724 1 The the DT cord-014597-66vd2mdu 1724 2 tricistronic tricistronic NNP cord-014597-66vd2mdu 1724 3 strategy strategy NN cord-014597-66vd2mdu 1724 4 provides provide VBZ cord-014597-66vd2mdu 1724 5 higher high JJR cord-014597-66vd2mdu 1724 6 productivity productivity NN cord-014597-66vd2mdu 1724 7 yields yield NNS cord-014597-66vd2mdu 1724 8 in in IN cord-014597-66vd2mdu 1724 9 HEK293 HEK293 NNP cord-014597-66vd2mdu 1724 10 and and CC cord-014597-66vd2mdu 1724 11 CHO CHO NNP cord-014597-66vd2mdu 1724 12 - - HYPH cord-014597-66vd2mdu 1724 13 S S NNP cord-014597-66vd2mdu 1724 14 cell cell NN cord-014597-66vd2mdu 1724 15 lines line NNS cord-014597-66vd2mdu 1724 16 for for IN cord-014597-66vd2mdu 1724 17 both both DT cord-014597-66vd2mdu 1724 18 recombinant recombinant JJ cord-014597-66vd2mdu 1724 19 proteins protein NNS cord-014597-66vd2mdu 1724 20 ( ( -LRB- cord-014597-66vd2mdu 1724 21 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1724 22 and and CC cord-014597-66vd2mdu 1724 23 Tzmb Tzmb NNP cord-014597-66vd2mdu 1724 24 - - HYPH cord-014597-66vd2mdu 1724 25 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1724 26 ) ) -RRB- cord-014597-66vd2mdu 1724 27 . . . cord-014597-66vd2mdu 1725 1 Regarding regard VBG cord-014597-66vd2mdu 1725 2 which which WDT cord-014597-66vd2mdu 1725 3 cell cell NN cord-014597-66vd2mdu 1725 4 line line NN cord-014597-66vd2mdu 1725 5 is be VBZ cord-014597-66vd2mdu 1725 6 the the DT cord-014597-66vd2mdu 1725 7 best good JJS cord-014597-66vd2mdu 1725 8 production production NN cord-014597-66vd2mdu 1725 9 host host NN cord-014597-66vd2mdu 1725 10 candidate candidate NN cord-014597-66vd2mdu 1725 11 , , , cord-014597-66vd2mdu 1725 12 HEK293 HEK293 NNP cord-014597-66vd2mdu 1725 13 achieved achieve VBD cord-014597-66vd2mdu 1725 14 higher high JJR cord-014597-66vd2mdu 1725 15 productivity productivity NN cord-014597-66vd2mdu 1725 16 than than IN cord-014597-66vd2mdu 1725 17 CHO CHO NNP cord-014597-66vd2mdu 1725 18 - - HYPH cord-014597-66vd2mdu 1725 19 S S NNP cord-014597-66vd2mdu 1725 20 cells cell NNS cord-014597-66vd2mdu 1725 21 for for IN cord-014597-66vd2mdu 1725 22 the the DT cord-014597-66vd2mdu 1725 23 two two CD cord-014597-66vd2mdu 1725 24 proteins protein NNS cord-014597-66vd2mdu 1725 25 tested test VBN cord-014597-66vd2mdu 1725 26 . . . cord-014597-66vd2mdu 1726 1 All all DT cord-014597-66vd2mdu 1726 2 constructions construction NNS cord-014597-66vd2mdu 1726 3 performed perform VBN cord-014597-66vd2mdu 1726 4 preserved preserve VBD cord-014597-66vd2mdu 1726 5 the the DT cord-014597-66vd2mdu 1726 6 binding bind VBG cord-014597-66vd2mdu 1726 7 affinity affinity NN cord-014597-66vd2mdu 1726 8 to to IN cord-014597-66vd2mdu 1726 9 its -PRON- PRP$ cord-014597-66vd2mdu 1726 10 antigen antigen NN cord-014597-66vd2mdu 1726 11 , , , cord-014597-66vd2mdu 1726 12 Trastuzumab Trastuzumab NNP cord-014597-66vd2mdu 1726 13 and and CC cord-014597-66vd2mdu 1726 14 Tzmb Tzmb NNP cord-014597-66vd2mdu 1726 15 - - HYPH cord-014597-66vd2mdu 1726 16 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1726 17 bind bind VBP cord-014597-66vd2mdu 1726 18 efficiently efficiently RB cord-014597-66vd2mdu 1726 19 to to IN cord-014597-66vd2mdu 1726 20 the the DT cord-014597-66vd2mdu 1726 21 HER2 HER2 NNP cord-014597-66vd2mdu 1726 22 antigen antigen NN cord-014597-66vd2mdu 1726 23 present present NN cord-014597-66vd2mdu 1726 24 in in IN cord-014597-66vd2mdu 1726 25 Skbr-3 Skbr-3 NNP cord-014597-66vd2mdu 1726 26 cells cell NNS cord-014597-66vd2mdu 1726 27 . . . cord-014597-66vd2mdu 1727 1 Finally finally RB cord-014597-66vd2mdu 1727 2 , , , cord-014597-66vd2mdu 1727 3 Tzmb Tzmb NNP cord-014597-66vd2mdu 1727 4 - - HYPH cord-014597-66vd2mdu 1727 5 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1727 6 does do VBZ cord-014597-66vd2mdu 1727 7 not not RB cord-014597-66vd2mdu 1727 8 present present VB cord-014597-66vd2mdu 1727 9 an an DT cord-014597-66vd2mdu 1727 10 improved improve VBN cord-014597-66vd2mdu 1727 11 antiproliferative antiproliferative JJ cord-014597-66vd2mdu 1727 12 effect effect NN cord-014597-66vd2mdu 1727 13 with with IN cord-014597-66vd2mdu 1727 14 respect respect NN cord-014597-66vd2mdu 1727 15 to to IN cord-014597-66vd2mdu 1727 16 Trastuzumab Trastuzumab NNP cord-014597-66vd2mdu 1727 17 when when WRB cord-014597-66vd2mdu 1727 18 compared compare VBN cord-014597-66vd2mdu 1727 19 by by IN cord-014597-66vd2mdu 1727 20 means mean NNS cord-014597-66vd2mdu 1727 21 of of IN cord-014597-66vd2mdu 1727 22 an an DT cord-014597-66vd2mdu 1727 23 in in FW cord-014597-66vd2mdu 1727 24 vitro vitro FW cord-014597-66vd2mdu 1727 25 assay assay NN cord-014597-66vd2mdu 1727 26 . . . cord-014597-66vd2mdu 1728 1 The the DT cord-014597-66vd2mdu 1728 2 genetic genetic JJ cord-014597-66vd2mdu 1728 3 engineering engineering NN cord-014597-66vd2mdu 1728 4 of of IN cord-014597-66vd2mdu 1728 5 patient patient NN cord-014597-66vd2mdu 1728 6 - - HYPH cord-014597-66vd2mdu 1728 7 specific specific JJ cord-014597-66vd2mdu 1728 8 T t NN cord-014597-66vd2mdu 1728 9 cells cell NNS cord-014597-66vd2mdu 1728 10 with with IN cord-014597-66vd2mdu 1728 11 lentiviral lentiviral JJ cord-014597-66vd2mdu 1728 12 vectors vector NNS cord-014597-66vd2mdu 1728 13 ( ( -LRB- cord-014597-66vd2mdu 1728 14 LVV LVV NNP cord-014597-66vd2mdu 1728 15 ) ) -RRB- cord-014597-66vd2mdu 1728 16 expressing express VBG cord-014597-66vd2mdu 1728 17 chimeric chimeric JJ cord-014597-66vd2mdu 1728 18 antigen antigen NN cord-014597-66vd2mdu 1728 19 receptors receptor NNS cord-014597-66vd2mdu 1728 20 ( ( -LRB- cord-014597-66vd2mdu 1728 21 CAR car NN cord-014597-66vd2mdu 1728 22 ) ) -RRB- cord-014597-66vd2mdu 1728 23 for for IN cord-014597-66vd2mdu 1728 24 late late JJ cord-014597-66vd2mdu 1728 25 phase phase NN cord-014597-66vd2mdu 1728 26 clinical clinical JJ cord-014597-66vd2mdu 1728 27 trials trial NNS cord-014597-66vd2mdu 1728 28 requires require VBZ cord-014597-66vd2mdu 1728 29 the the DT cord-014597-66vd2mdu 1728 30 large large JJ cord-014597-66vd2mdu 1728 31 - - HYPH cord-014597-66vd2mdu 1728 32 scale scale NN cord-014597-66vd2mdu 1728 33 manufacture manufacture NN cord-014597-66vd2mdu 1728 34 of of IN cord-014597-66vd2mdu 1728 35 high high JJ cord-014597-66vd2mdu 1728 36 - - HYPH cord-014597-66vd2mdu 1728 37 titer titer NN cord-014597-66vd2mdu 1728 38 vector vector NN cord-014597-66vd2mdu 1728 39 stocks stock NNS cord-014597-66vd2mdu 1728 40 . . . cord-014597-66vd2mdu 1729 1 The the DT cord-014597-66vd2mdu 1729 2 state state NN cord-014597-66vd2mdu 1729 3 - - HYPH cord-014597-66vd2mdu 1729 4 of of IN cord-014597-66vd2mdu 1729 5 - - HYPH cord-014597-66vd2mdu 1729 6 the the DT cord-014597-66vd2mdu 1729 7 - - HYPH cord-014597-66vd2mdu 1729 8 art art NN cord-014597-66vd2mdu 1729 9 production production NN cord-014597-66vd2mdu 1729 10 of of IN cord-014597-66vd2mdu 1729 11 LVV LVV NNP cord-014597-66vd2mdu 1729 12 is be VBZ cord-014597-66vd2mdu 1729 13 based base VBN cord-014597-66vd2mdu 1729 14 on on IN cord-014597-66vd2mdu 1729 15 10-to 10-to CD cord-014597-66vd2mdu 1729 16 40layer 40layer CD cord-014597-66vd2mdu 1729 17 cell cell NN cord-014597-66vd2mdu 1729 18 factories factory NNS cord-014597-66vd2mdu 1729 19 transiently transiently RB cord-014597-66vd2mdu 1729 20 transfected transfecte VBN cord-014597-66vd2mdu 1729 21 in in IN cord-014597-66vd2mdu 1729 22 the the DT cord-014597-66vd2mdu 1729 23 presence presence NN cord-014597-66vd2mdu 1729 24 of of IN cord-014597-66vd2mdu 1729 25 serum serum NN cord-014597-66vd2mdu 1729 26 . . . cord-014597-66vd2mdu 1730 1 This this DT cord-014597-66vd2mdu 1730 2 manufacturing manufacturing NN cord-014597-66vd2mdu 1730 3 process process NN cord-014597-66vd2mdu 1730 4 is be VBZ cord-014597-66vd2mdu 1730 5 extremely extremely RB cord-014597-66vd2mdu 1730 6 limited limit VBN cord-014597-66vd2mdu 1730 7 by by IN cord-014597-66vd2mdu 1730 8 its -PRON- PRP$ cord-014597-66vd2mdu 1730 9 labor labor NN cord-014597-66vd2mdu 1730 10 intensity intensity NN cord-014597-66vd2mdu 1730 11 , , , cord-014597-66vd2mdu 1730 12 open open JJ cord-014597-66vd2mdu 1730 13 - - HYPH cord-014597-66vd2mdu 1730 14 system system NN cord-014597-66vd2mdu 1730 15 handling handling NN cord-014597-66vd2mdu 1730 16 operations operation NNS cord-014597-66vd2mdu 1730 17 , , , cord-014597-66vd2mdu 1730 18 its -PRON- PRP$ cord-014597-66vd2mdu 1730 19 requirements requirement NNS cord-014597-66vd2mdu 1730 20 for for IN cord-014597-66vd2mdu 1730 21 significant significant JJ cord-014597-66vd2mdu 1730 22 incubator incubator NN cord-014597-66vd2mdu 1730 23 space space NN cord-014597-66vd2mdu 1730 24 plus plus CC cord-014597-66vd2mdu 1730 25 costs cost NNS cord-014597-66vd2mdu 1730 26 and and CC cord-014597-66vd2mdu 1730 27 patience patience NN cord-014597-66vd2mdu 1730 28 risk risk NN cord-014597-66vd2mdu 1730 29 due due JJ cord-014597-66vd2mdu 1730 30 to to IN cord-014597-66vd2mdu 1730 31 presence presence NN cord-014597-66vd2mdu 1730 32 of of IN cord-014597-66vd2mdu 1730 33 serum serum NN cord-014597-66vd2mdu 1730 34 . . . cord-014597-66vd2mdu 1731 1 To to TO cord-014597-66vd2mdu 1731 2 circumvent circumvent VB cord-014597-66vd2mdu 1731 3 these these DT cord-014597-66vd2mdu 1731 4 limitations limitation NNS cord-014597-66vd2mdu 1731 5 , , , cord-014597-66vd2mdu 1731 6 this this DT cord-014597-66vd2mdu 1731 7 study study NN cord-014597-66vd2mdu 1731 8 aims aim VBZ cord-014597-66vd2mdu 1731 9 to to TO cord-014597-66vd2mdu 1731 10 develop develop VB cord-014597-66vd2mdu 1731 11 a a DT cord-014597-66vd2mdu 1731 12 stable stable JJ cord-014597-66vd2mdu 1731 13 and and CC cord-014597-66vd2mdu 1731 14 serum serum NN cord-014597-66vd2mdu 1731 15 - - HYPH cord-014597-66vd2mdu 1731 16 free free JJ cord-014597-66vd2mdu 1731 17 process process NN cord-014597-66vd2mdu 1731 18 to to TO cord-014597-66vd2mdu 1731 19 produce produce VB cord-014597-66vd2mdu 1731 20 LVV LVV NNP cord-014597-66vd2mdu 1731 21 with with IN cord-014597-66vd2mdu 1731 22 PEI PEI NNP cord-014597-66vd2mdu 1731 23 - - HYPH cord-014597-66vd2mdu 1731 24 mediated mediate VBN cord-014597-66vd2mdu 1731 25 transfection transfection NN cord-014597-66vd2mdu 1731 26 . . . cord-014597-66vd2mdu 1732 1 In in IN cord-014597-66vd2mdu 1732 2 addition addition NN cord-014597-66vd2mdu 1732 3 , , , cord-014597-66vd2mdu 1732 4 this this DT cord-014597-66vd2mdu 1732 5 study study NN cord-014597-66vd2mdu 1732 6 also also RB cord-014597-66vd2mdu 1732 7 focuses focus VBZ cord-014597-66vd2mdu 1732 8 on on IN cord-014597-66vd2mdu 1732 9 the the DT cord-014597-66vd2mdu 1732 10 development development NN cord-014597-66vd2mdu 1732 11 of of IN cord-014597-66vd2mdu 1732 12 a a DT cord-014597-66vd2mdu 1732 13 a a DT cord-014597-66vd2mdu 1732 14 c c NN cord-014597-66vd2mdu 1732 15 b b NN cord-014597-66vd2mdu 1732 16 d d NNP cord-014597-66vd2mdu 1732 17 Fig Fig NNP cord-014597-66vd2mdu 1732 18 . . . cord-014597-66vd2mdu 1733 1 1 1 LS cord-014597-66vd2mdu 1733 2 ( ( -LRB- cord-014597-66vd2mdu 1733 3 abstract abstract NNP cord-014597-66vd2mdu 1733 4 P-276 P-276 NNP cord-014597-66vd2mdu 1733 5 ) ) -RRB- cord-014597-66vd2mdu 1733 6 . . . cord-014597-66vd2mdu 1734 1 Expression expression NN cord-014597-66vd2mdu 1734 2 of of IN cord-014597-66vd2mdu 1734 3 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1734 4 ( ( -LRB- cord-014597-66vd2mdu 1734 5 a a LS cord-014597-66vd2mdu 1734 6 ) ) -RRB- cord-014597-66vd2mdu 1734 7 and and CC cord-014597-66vd2mdu 1735 1 Trastuzumab Trastuzumab NNP cord-014597-66vd2mdu 1735 2 - - HYPH cord-014597-66vd2mdu 1735 3 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1735 4 ( ( -LRB- cord-014597-66vd2mdu 1735 5 b b NN cord-014597-66vd2mdu 1735 6 ) ) -RRB- cord-014597-66vd2mdu 1735 7 from from IN cord-014597-66vd2mdu 1735 8 bicistronic bicistronic JJ cord-014597-66vd2mdu 1735 9 strategy strategy NN cord-014597-66vd2mdu 1735 10 ( ( -LRB- cord-014597-66vd2mdu 1735 11 BC BC NNP cord-014597-66vd2mdu 1735 12 ) ) -RRB- cord-014597-66vd2mdu 1735 13 and and CC cord-014597-66vd2mdu 1735 14 tricistronic tricistronic NNP cord-014597-66vd2mdu 1735 15 strategy strategy NN cord-014597-66vd2mdu 1735 16 ( ( -LRB- cord-014597-66vd2mdu 1735 17 TRI TRI NNP cord-014597-66vd2mdu 1735 18 ) ) -RRB- cord-014597-66vd2mdu 1735 19 with with IN cord-014597-66vd2mdu 1735 20 CHO CHO NNP cord-014597-66vd2mdu 1735 21 - - HYPH cord-014597-66vd2mdu 1735 22 S S NNP cord-014597-66vd2mdu 1735 23 and and CC cord-014597-66vd2mdu 1735 24 HEK293 HEK293 NNP cord-014597-66vd2mdu 1735 25 cells cell NNS cord-014597-66vd2mdu 1735 26 . . . cord-014597-66vd2mdu 1736 1 Relative relative JJ cord-014597-66vd2mdu 1736 2 specific specific JJ cord-014597-66vd2mdu 1736 3 productivity productivity NN cord-014597-66vd2mdu 1736 4 units unit NNS cord-014597-66vd2mdu 1736 5 are be VBP cord-014597-66vd2mdu 1736 6 used use VBN cord-014597-66vd2mdu 1736 7 for for IN cord-014597-66vd2mdu 1736 8 comparing compare VBG cord-014597-66vd2mdu 1736 9 the the DT cord-014597-66vd2mdu 1736 10 different different JJ cord-014597-66vd2mdu 1736 11 strategies strategy NNS cord-014597-66vd2mdu 1736 12 . . . cord-014597-66vd2mdu 1737 1 c c NNP cord-014597-66vd2mdu 1737 2 Antigen Antigen NNP cord-014597-66vd2mdu 1737 3 binding bind VBG cord-014597-66vd2mdu 1737 4 analysis analysis NN cord-014597-66vd2mdu 1737 5 of of IN cord-014597-66vd2mdu 1737 6 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1737 7 and and CC cord-014597-66vd2mdu 1737 8 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1737 9 - - HYPH cord-014597-66vd2mdu 1737 10 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1737 11 . . . cord-014597-66vd2mdu 1738 1 d d NNP cord-014597-66vd2mdu 1739 1 Antiproliferative antiproliferative JJ cord-014597-66vd2mdu 1739 2 activity activity NN cord-014597-66vd2mdu 1739 3 of of IN cord-014597-66vd2mdu 1739 4 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1739 5 and and CC cord-014597-66vd2mdu 1739 6 Trastuzumab Trastuzumab NNPS cord-014597-66vd2mdu 1739 7 - - HYPH cord-014597-66vd2mdu 1739 8 IFNα2b IFNα2b NNP cord-014597-66vd2mdu 1739 9 on on IN cord-014597-66vd2mdu 1739 10 Sk Sk NNP cord-014597-66vd2mdu 1739 11 - - HYPH cord-014597-66vd2mdu 1739 12 br-3 br-3 NNP cord-014597-66vd2mdu 1739 13 cells cell NNS cord-014597-66vd2mdu 1739 14 production production NN cord-014597-66vd2mdu 1739 15 system system NN cord-014597-66vd2mdu 1739 16 not not RB cord-014597-66vd2mdu 1739 17 only only RB cord-014597-66vd2mdu 1739 18 using use VBG cord-014597-66vd2mdu 1739 19 a a DT cord-014597-66vd2mdu 1739 20 GFP GFP NNP cord-014597-66vd2mdu 1739 21 marker marker NN cord-014597-66vd2mdu 1739 22 but but CC cord-014597-66vd2mdu 1739 23 also also RB cord-014597-66vd2mdu 1739 24 a a DT cord-014597-66vd2mdu 1739 25 therapeutically therapeutically RB cord-014597-66vd2mdu 1739 26 relevant relevant JJ cord-014597-66vd2mdu 1739 27 transgene transgene NN cord-014597-66vd2mdu 1739 28 ( ( -LRB- cord-014597-66vd2mdu 1739 29 CD20-CAR CD20-CAR NNP cord-014597-66vd2mdu 1739 30 ) ) -RRB- cord-014597-66vd2mdu 1739 31 [ [ -LRB- cord-014597-66vd2mdu 1739 32 1 1 CD cord-014597-66vd2mdu 1739 33 ] ] -RRB- cord-014597-66vd2mdu 1739 34 . . . cord-014597-66vd2mdu 1740 1 Therefore therefore RB cord-014597-66vd2mdu 1740 2 , , , cord-014597-66vd2mdu 1740 3 three three CD cord-014597-66vd2mdu 1740 4 different different JJ cord-014597-66vd2mdu 1740 5 cell cell NN cord-014597-66vd2mdu 1740 6 lines line NNS cord-014597-66vd2mdu 1740 7 ( ( -LRB- cord-014597-66vd2mdu 1740 8 HEK HEK NNP cord-014597-66vd2mdu 1740 9 293 293 CD cord-014597-66vd2mdu 1740 10 , , , cord-014597-66vd2mdu 1740 11 293 293 CD cord-014597-66vd2mdu 1740 12 T t NN cord-014597-66vd2mdu 1740 13 , , , cord-014597-66vd2mdu 1740 14 293FT 293FT NNP cord-014597-66vd2mdu 1740 15 ) ) -RRB- cord-014597-66vd2mdu 1740 16 were be VBD cord-014597-66vd2mdu 1740 17 investigated investigate VBN cord-014597-66vd2mdu 1740 18 concerning concern VBG cord-014597-66vd2mdu 1740 19 their -PRON- PRP$ cord-014597-66vd2mdu 1740 20 productivity productivity NN cord-014597-66vd2mdu 1740 21 of of IN cord-014597-66vd2mdu 1740 22 LVV LVV NNP cord-014597-66vd2mdu 1740 23 and and CC cord-014597-66vd2mdu 1740 24 their -PRON- PRP$ cord-014597-66vd2mdu 1740 25 growing grow VBG cord-014597-66vd2mdu 1740 26 behavior behavior NN cord-014597-66vd2mdu 1740 27 in in IN cord-014597-66vd2mdu 1740 28 the the DT cord-014597-66vd2mdu 1740 29 in in IN cord-014597-66vd2mdu 1740 30 - - HYPH cord-014597-66vd2mdu 1740 31 house house NN cord-014597-66vd2mdu 1740 32 serum serum NN cord-014597-66vd2mdu 1740 33 - - HYPH cord-014597-66vd2mdu 1740 34 free free JJ cord-014597-66vd2mdu 1740 35 medium medium JJ cord-014597-66vd2mdu 1740 36 TransMACS transmac NNS cord-014597-66vd2mdu 1740 37 . . . cord-014597-66vd2mdu 1741 1 As as IN cord-014597-66vd2mdu 1741 2 part part NN cord-014597-66vd2mdu 1741 3 of of IN cord-014597-66vd2mdu 1741 4 this this DT cord-014597-66vd2mdu 1741 5 , , , cord-014597-66vd2mdu 1741 6 Design Design NNP cord-014597-66vd2mdu 1741 7 of of IN cord-014597-66vd2mdu 1741 8 Experiment Experiment NNP cord-014597-66vd2mdu 1741 9 was be VBD cord-014597-66vd2mdu 1741 10 used use VBN cord-014597-66vd2mdu 1741 11 to to TO cord-014597-66vd2mdu 1741 12 investigate investigate VB cord-014597-66vd2mdu 1741 13 the the DT cord-014597-66vd2mdu 1741 14 optimal optimal JJ cord-014597-66vd2mdu 1741 15 conditions condition NNS cord-014597-66vd2mdu 1741 16 for for IN cord-014597-66vd2mdu 1741 17 PEI/ pei/ JJ cord-014597-66vd2mdu 1741 18 DNA dna NN cord-014597-66vd2mdu 1741 19 - - HYPH cord-014597-66vd2mdu 1741 20 transfection transfection NN cord-014597-66vd2mdu 1741 21 . . . cord-014597-66vd2mdu 1742 1 Furthermore furthermore RB cord-014597-66vd2mdu 1742 2 , , , cord-014597-66vd2mdu 1742 3 this this DT cord-014597-66vd2mdu 1742 4 statistical statistical JJ cord-014597-66vd2mdu 1742 5 approach approach NN cord-014597-66vd2mdu 1742 6 was be VBD cord-014597-66vd2mdu 1742 7 used use VBN cord-014597-66vd2mdu 1742 8 focusing focus VBG cord-014597-66vd2mdu 1742 9 an an DT cord-014597-66vd2mdu 1742 10 ideal ideal JJ cord-014597-66vd2mdu 1742 11 ratio ratio NN cord-014597-66vd2mdu 1742 12 between between IN cord-014597-66vd2mdu 1742 13 the the DT cord-014597-66vd2mdu 1742 14 3rd 3rd JJ cord-014597-66vd2mdu 1742 15 generation generation NN cord-014597-66vd2mdu 1742 16 plasmids plasmid NNS cord-014597-66vd2mdu 1742 17 ( ( -LRB- cord-014597-66vd2mdu 1742 18 transfer transfer NN cord-014597-66vd2mdu 1742 19 plasmid plasmid NN cord-014597-66vd2mdu 1742 20 CD20-CAR CD20-CAR NNP cord-014597-66vd2mdu 1742 21 or or CC cord-014597-66vd2mdu 1742 22 GFP GFP NNP cord-014597-66vd2mdu 1742 23 , , , cord-014597-66vd2mdu 1742 24 envelope envelope NN cord-014597-66vd2mdu 1742 25 plasmid plasmid NN cord-014597-66vd2mdu 1742 26 , , , cord-014597-66vd2mdu 1742 27 packaging packaging NN cord-014597-66vd2mdu 1742 28 plasmids plasmid NNS cord-014597-66vd2mdu 1742 29 ) ) -RRB- cord-014597-66vd2mdu 1742 30 . . . cord-014597-66vd2mdu 1743 1 In in IN cord-014597-66vd2mdu 1743 2 addition addition NN cord-014597-66vd2mdu 1743 3 , , , cord-014597-66vd2mdu 1743 4 different different JJ cord-014597-66vd2mdu 1743 5 enhancers enhancer NNS cord-014597-66vd2mdu 1743 6 ( ( -LRB- cord-014597-66vd2mdu 1743 7 sodium sodium NN cord-014597-66vd2mdu 1743 8 butyrate butyrate NN cord-014597-66vd2mdu 1743 9 , , , cord-014597-66vd2mdu 1743 10 lithium lithium NN cord-014597-66vd2mdu 1743 11 acetate acetate NN cord-014597-66vd2mdu 1743 12 , , , cord-014597-66vd2mdu 1743 13 caffeine caffeine NN cord-014597-66vd2mdu 1743 14 , , , cord-014597-66vd2mdu 1743 15 trichostatin trichostatin NNP cord-014597-66vd2mdu 1743 16 A A NNP cord-014597-66vd2mdu 1743 17 , , , cord-014597-66vd2mdu 1743 18 cholesterol cholesterol NN cord-014597-66vd2mdu 1743 19 , , , cord-014597-66vd2mdu 1743 20 hydroxyurea hydroxyurea NNP cord-014597-66vd2mdu 1743 21 , , , cord-014597-66vd2mdu 1743 22 valproic valproic NN cord-014597-66vd2mdu 1743 23 acid acid NN cord-014597-66vd2mdu 1743 24 ) ) -RRB- cord-014597-66vd2mdu 1743 25 were be VBD cord-014597-66vd2mdu 1743 26 investigated investigate VBN cord-014597-66vd2mdu 1743 27 concerning concern VBG cord-014597-66vd2mdu 1743 28 their -PRON- PRP$ cord-014597-66vd2mdu 1743 29 effects effect NNS cord-014597-66vd2mdu 1743 30 on on IN cord-014597-66vd2mdu 1743 31 productivity productivity NN cord-014597-66vd2mdu 1743 32 comparing compare VBG cord-014597-66vd2mdu 1743 33 HEK HEK NNP cord-014597-66vd2mdu 1743 34 cultures culture NNS cord-014597-66vd2mdu 1743 35 producing produce VBG cord-014597-66vd2mdu 1743 36 LVV lvv NN cord-014597-66vd2mdu 1743 37 encoding encode VBG cord-014597-66vd2mdu 1743 38 for for IN cord-014597-66vd2mdu 1743 39 GFP gfp NN cord-014597-66vd2mdu 1743 40 - - HYPH cord-014597-66vd2mdu 1743 41 marker marker NN cord-014597-66vd2mdu 1743 42 or or CC cord-014597-66vd2mdu 1743 43 CD20-CAR cd20-car NN cord-014597-66vd2mdu 1743 44 . . . cord-014597-66vd2mdu 1744 1 Concerning concern VBG cord-014597-66vd2mdu 1744 2 productivity productivity NN cord-014597-66vd2mdu 1744 3 and and CC cord-014597-66vd2mdu 1744 4 growing grow VBG cord-014597-66vd2mdu 1744 5 behavior behavior NN cord-014597-66vd2mdu 1744 6 , , , cord-014597-66vd2mdu 1744 7 HEK HEK NNP cord-014597-66vd2mdu 1744 8 293 293 CD cord-014597-66vd2mdu 1744 9 T T NNP cord-014597-66vd2mdu 1744 10 was be VBD cord-014597-66vd2mdu 1744 11 the the DT cord-014597-66vd2mdu 1744 12 favored favored JJ cord-014597-66vd2mdu 1744 13 cell cell NN cord-014597-66vd2mdu 1744 14 line line NN cord-014597-66vd2mdu 1744 15 for for IN cord-014597-66vd2mdu 1744 16 our -PRON- PRP$ cord-014597-66vd2mdu 1744 17 serum serum NN cord-014597-66vd2mdu 1744 18 - - HYPH cord-014597-66vd2mdu 1744 19 free free JJ cord-014597-66vd2mdu 1744 20 LV LV NNP cord-014597-66vd2mdu 1744 21 manufacturing manufacturing NN cord-014597-66vd2mdu 1744 22 process process NN cord-014597-66vd2mdu 1744 23 . . . cord-014597-66vd2mdu 1745 1 In in IN cord-014597-66vd2mdu 1745 2 addition addition NN cord-014597-66vd2mdu 1745 3 , , , cord-014597-66vd2mdu 1745 4 an an DT cord-014597-66vd2mdu 1745 5 additive additive NN cord-014597-66vd2mdu 1745 6 screen screen NN cord-014597-66vd2mdu 1745 7 revealed reveal VBD cord-014597-66vd2mdu 1745 8 that that IN cord-014597-66vd2mdu 1745 9 sodium sodium NN cord-014597-66vd2mdu 1745 10 butyrate butyrate NN cord-014597-66vd2mdu 1745 11 alone alone RB cord-014597-66vd2mdu 1745 12 had have VBD cord-014597-66vd2mdu 1745 13 the the DT cord-014597-66vd2mdu 1745 14 most most RBS cord-014597-66vd2mdu 1745 15 promising promising JJ cord-014597-66vd2mdu 1745 16 effect effect NN cord-014597-66vd2mdu 1745 17 on on IN cord-014597-66vd2mdu 1745 18 both both DT cord-014597-66vd2mdu 1745 19 GFP GFP NNP cord-014597-66vd2mdu 1745 20 - - HYPH cord-014597-66vd2mdu 1745 21 LVV LVV NNP cord-014597-66vd2mdu 1745 22 and and CC cord-014597-66vd2mdu 1745 23 CD20-CAR CD20-CAR NNP cord-014597-66vd2mdu 1745 24 - - HYPH cord-014597-66vd2mdu 1745 25 LVV LVV NNP cord-014597-66vd2mdu 1745 26 production production NN cord-014597-66vd2mdu 1745 27 . . . cord-014597-66vd2mdu 1746 1 After after IN cord-014597-66vd2mdu 1746 2 PEI PEI NNP cord-014597-66vd2mdu 1746 3 / / SYM cord-014597-66vd2mdu 1746 4 DNA dna NN cord-014597-66vd2mdu 1746 5 titration titration NN cord-014597-66vd2mdu 1746 6 , , , cord-014597-66vd2mdu 1746 7 we -PRON- PRP cord-014597-66vd2mdu 1746 8 finally finally RB cord-014597-66vd2mdu 1746 9 could could MD cord-014597-66vd2mdu 1746 10 increase increase VB cord-014597-66vd2mdu 1746 11 LVV LVV NNP cord-014597-66vd2mdu 1746 12 productivity productivity NN cord-014597-66vd2mdu 1746 13 by by IN cord-014597-66vd2mdu 1746 14 lowering lower VBG cord-014597-66vd2mdu 1746 15 PEI PEI NNP cord-014597-66vd2mdu 1746 16 / / SYM cord-014597-66vd2mdu 1746 17 DNA dna NN cord-014597-66vd2mdu 1746 18 amount amount NN cord-014597-66vd2mdu 1746 19 at at IN cord-014597-66vd2mdu 1746 20 higher high JJR cord-014597-66vd2mdu 1746 21 cell cell NN cord-014597-66vd2mdu 1746 22 densities density NNS cord-014597-66vd2mdu 1746 23 referred refer VBN cord-014597-66vd2mdu 1746 24 to to IN cord-014597-66vd2mdu 1746 25 our -PRON- PRP$ cord-014597-66vd2mdu 1746 26 standard standard JJ cord-014597-66vd2mdu 1746 27 transfection transfection NN cord-014597-66vd2mdu 1746 28 protocol protocol NN cord-014597-66vd2mdu 1746 29 . . . cord-014597-66vd2mdu 1747 1 Furthermore furthermore RB cord-014597-66vd2mdu 1747 2 , , , cord-014597-66vd2mdu 1747 3 the the DT cord-014597-66vd2mdu 1747 4 titration titration NN cord-014597-66vd2mdu 1747 5 for for IN cord-014597-66vd2mdu 1747 6 the the DT cord-014597-66vd2mdu 1747 7 optimal optimal JJ cord-014597-66vd2mdu 1747 8 plasmid plasmid NN cord-014597-66vd2mdu 1747 9 ration ration NN cord-014597-66vd2mdu 1747 10 revealed reveal VBN cord-014597-66vd2mdu 1747 11 , , , cord-014597-66vd2mdu 1747 12 that that IN cord-014597-66vd2mdu 1747 13 for for IN cord-014597-66vd2mdu 1747 14 large large JJ cord-014597-66vd2mdu 1747 15 transfer transfer NN cord-014597-66vd2mdu 1747 16 constructs construct VBZ cord-014597-66vd2mdu 1747 17 higher high JJR cord-014597-66vd2mdu 1747 18 amounts amount NNS cord-014597-66vd2mdu 1747 19 of of IN cord-014597-66vd2mdu 1747 20 transfer transfer NN cord-014597-66vd2mdu 1747 21 plasmid plasmid NN cord-014597-66vd2mdu 1747 22 are be VBP cord-014597-66vd2mdu 1747 23 required require VBN cord-014597-66vd2mdu 1747 24 than than IN cord-014597-66vd2mdu 1747 25 for for IN cord-014597-66vd2mdu 1747 26 smaller small JJR cord-014597-66vd2mdu 1747 27 constructs construct NNS cord-014597-66vd2mdu 1747 28 to to TO cord-014597-66vd2mdu 1747 29 achieve achieve VB cord-014597-66vd2mdu 1747 30 a a DT cord-014597-66vd2mdu 1747 31 high high JJ cord-014597-66vd2mdu 1747 32 productivity productivity NN cord-014597-66vd2mdu 1747 33 ( ( -LRB- cord-014597-66vd2mdu 1747 34 Fig fig NN cord-014597-66vd2mdu 1747 35 . . . cord-014597-66vd2mdu 1747 36 1 1 CD cord-014597-66vd2mdu 1747 37 ) ) -RRB- cord-014597-66vd2mdu 1747 38 . . . cord-014597-66vd2mdu 1748 1 The the DT cord-014597-66vd2mdu 1748 2 outcome outcome NN cord-014597-66vd2mdu 1748 3 of of IN cord-014597-66vd2mdu 1748 4 these these DT cord-014597-66vd2mdu 1748 5 experiments experiment NNS cord-014597-66vd2mdu 1748 6 enabled enable VBD cord-014597-66vd2mdu 1748 7 the the DT cord-014597-66vd2mdu 1748 8 development development NN cord-014597-66vd2mdu 1748 9 of of IN cord-014597-66vd2mdu 1748 10 a a DT cord-014597-66vd2mdu 1748 11 robust robust JJ cord-014597-66vd2mdu 1748 12 HEK293 HEK293 NNP cord-014597-66vd2mdu 1748 13 T t NN cord-014597-66vd2mdu 1748 14 based base VBN cord-014597-66vd2mdu 1748 15 process process NN cord-014597-66vd2mdu 1748 16 to to TO cord-014597-66vd2mdu 1748 17 produce produce VB cord-014597-66vd2mdu 1748 18 clinical clinical JJ cord-014597-66vd2mdu 1748 19 relevant relevant JJ cord-014597-66vd2mdu 1748 20 LVV LVV NNP cord-014597-66vd2mdu 1748 21 under under IN cord-014597-66vd2mdu 1748 22 serumfree serumfree JJ cord-014597-66vd2mdu 1748 23 conditions condition NNS cord-014597-66vd2mdu 1748 24 . . . cord-014597-66vd2mdu 1749 1 Furthermore furthermore RB cord-014597-66vd2mdu 1749 2 , , , cord-014597-66vd2mdu 1749 3 it -PRON- PRP cord-014597-66vd2mdu 1749 4 provides provide VBZ cord-014597-66vd2mdu 1749 5 an an DT cord-014597-66vd2mdu 1749 6 insight insight NN cord-014597-66vd2mdu 1749 7 how how WRB cord-014597-66vd2mdu 1749 8 therapeutic therapeutic JJ cord-014597-66vd2mdu 1749 9 genes gene NNS cord-014597-66vd2mdu 1749 10 and and CC cord-014597-66vd2mdu 1749 11 the the DT cord-014597-66vd2mdu 1749 12 expression expression NN cord-014597-66vd2mdu 1749 13 of of IN cord-014597-66vd2mdu 1749 14 its -PRON- PRP$ cord-014597-66vd2mdu 1749 15 transgene transgene NN cord-014597-66vd2mdu 1749 16 can can MD cord-014597-66vd2mdu 1749 17 influence influence VB cord-014597-66vd2mdu 1749 18 cell cell NN cord-014597-66vd2mdu 1749 19 productivity productivity NN cord-014597-66vd2mdu 1749 20 . . . cord-014597-66vd2mdu 1750 1 led lead VBN cord-014597-66vd2mdu 1750 2 to to IN cord-014597-66vd2mdu 1750 3 a a DT cord-014597-66vd2mdu 1750 4 vast vast JJ cord-014597-66vd2mdu 1750 5 increase increase NN cord-014597-66vd2mdu 1750 6 in in IN cord-014597-66vd2mdu 1750 7 productivity productivity NN cord-014597-66vd2mdu 1750 8 , , , cord-014597-66vd2mdu 1750 9 CHO CHO NNP cord-014597-66vd2mdu 1750 10 cells cell NNS cord-014597-66vd2mdu 1750 11 yield yield VBP cord-014597-66vd2mdu 1750 12 less less JJR cord-014597-66vd2mdu 1750 13 than than IN cord-014597-66vd2mdu 1750 14 other other JJ cord-014597-66vd2mdu 1750 15 expression expression NN cord-014597-66vd2mdu 1750 16 systems system NNS cord-014597-66vd2mdu 1750 17 like like IN cord-014597-66vd2mdu 1750 18 yeast yeast NN cord-014597-66vd2mdu 1750 19 or or CC cord-014597-66vd2mdu 1750 20 bacteria bacteria NNS cord-014597-66vd2mdu 1750 21 [ [ -LRB- cord-014597-66vd2mdu 1750 22 1 1 CD cord-014597-66vd2mdu 1750 23 ] ] -RRB- cord-014597-66vd2mdu 1750 24 . . . cord-014597-66vd2mdu 1751 1 To to TO cord-014597-66vd2mdu 1751 2 improve improve VB cord-014597-66vd2mdu 1751 3 yields yield NNS cord-014597-66vd2mdu 1751 4 and and CC cord-014597-66vd2mdu 1751 5 find find VB cord-014597-66vd2mdu 1751 6 beneficial beneficial JJ cord-014597-66vd2mdu 1751 7 bioprocess bioprocess NN cord-014597-66vd2mdu 1751 8 phenotypes phenotype NNS cord-014597-66vd2mdu 1751 9 , , , cord-014597-66vd2mdu 1751 10 genetic genetic JJ cord-014597-66vd2mdu 1751 11 engineering engineering NN cord-014597-66vd2mdu 1751 12 plays play VBZ cord-014597-66vd2mdu 1751 13 an an DT cord-014597-66vd2mdu 1751 14 essential essential JJ cord-014597-66vd2mdu 1751 15 role role NN cord-014597-66vd2mdu 1751 16 in in IN cord-014597-66vd2mdu 1751 17 recent recent JJ cord-014597-66vd2mdu 1751 18 research research NN cord-014597-66vd2mdu 1751 19 . . . cord-014597-66vd2mdu 1752 1 The the DT cord-014597-66vd2mdu 1752 2 miR-23 mir-23 NN cord-014597-66vd2mdu 1752 3 cluster cluster NN cord-014597-66vd2mdu 1752 4 with with IN cord-014597-66vd2mdu 1752 5 its -PRON- PRP$ cord-014597-66vd2mdu 1752 6 genomic genomic JJ cord-014597-66vd2mdu 1752 7 paralogues paralogue NNS cord-014597-66vd2mdu 1752 8 ( ( -LRB- cord-014597-66vd2mdu 1752 9 miR-23a miR-23a NNP cord-014597-66vd2mdu 1752 10 and and CC cord-014597-66vd2mdu 1752 11 miR-23b miR-23b NNP cord-014597-66vd2mdu 1752 12 ) ) -RRB- cord-014597-66vd2mdu 1752 13 was be VBD cord-014597-66vd2mdu 1752 14 first first RB cord-014597-66vd2mdu 1752 15 identified identify VBN cord-014597-66vd2mdu 1752 16 as as IN cord-014597-66vd2mdu 1752 17 differentially differentially RB cord-014597-66vd2mdu 1752 18 expressed express VBN cord-014597-66vd2mdu 1752 19 during during IN cord-014597-66vd2mdu 1752 20 temperature temperature NN cord-014597-66vd2mdu 1752 21 shift shift NN cord-014597-66vd2mdu 1752 22 , , , cord-014597-66vd2mdu 1752 23 suggesting suggest VBG cord-014597-66vd2mdu 1752 24 its -PRON- PRP$ cord-014597-66vd2mdu 1752 25 role role NN cord-014597-66vd2mdu 1752 26 in in IN cord-014597-66vd2mdu 1752 27 proliferation proliferation NN cord-014597-66vd2mdu 1752 28 and and CC cord-014597-66vd2mdu 1752 29 productivity productivity NN cord-014597-66vd2mdu 1752 30 [ [ -LRB- cord-014597-66vd2mdu 1752 31 2 2 CD cord-014597-66vd2mdu 1752 32 ] ] -RRB- cord-014597-66vd2mdu 1752 33 . . . cord-014597-66vd2mdu 1753 1 The the DT cord-014597-66vd2mdu 1753 2 common common JJ cord-014597-66vd2mdu 1753 3 approach approach NN cord-014597-66vd2mdu 1753 4 to to TO cord-014597-66vd2mdu 1753 5 deplete deplete VB cord-014597-66vd2mdu 1753 6 miRNAs miRNAs NNP cord-014597-66vd2mdu 1753 7 is be VBZ cord-014597-66vd2mdu 1753 8 the the DT cord-014597-66vd2mdu 1753 9 use use NN cord-014597-66vd2mdu 1753 10 of of IN cord-014597-66vd2mdu 1753 11 a a DT cord-014597-66vd2mdu 1753 12 sponge sponge NN cord-014597-66vd2mdu 1753 13 decoy decoy NN cord-014597-66vd2mdu 1753 14 which which WDT cord-014597-66vd2mdu 1753 15 , , , cord-014597-66vd2mdu 1753 16 requires require VBZ cord-014597-66vd2mdu 1753 17 the the DT cord-014597-66vd2mdu 1753 18 introduction introduction NN cord-014597-66vd2mdu 1753 19 of of IN cord-014597-66vd2mdu 1753 20 reporter reporter NN cord-014597-66vd2mdu 1753 21 genes gene NNS cord-014597-66vd2mdu 1753 22 . . . cord-014597-66vd2mdu 1754 1 As as IN cord-014597-66vd2mdu 1754 2 an an DT cord-014597-66vd2mdu 1754 3 alternative alternative NN cord-014597-66vd2mdu 1754 4 this this DT cord-014597-66vd2mdu 1754 5 work work NN cord-014597-66vd2mdu 1754 6 aims aim VBZ cord-014597-66vd2mdu 1754 7 to to TO cord-014597-66vd2mdu 1754 8 knockdown knockdown VB cord-014597-66vd2mdu 1754 9 miRNA miRNA NNP cord-014597-66vd2mdu 1754 10 expression expression NN cord-014597-66vd2mdu 1754 11 using use VBG cord-014597-66vd2mdu 1754 12 the the DT cord-014597-66vd2mdu 1754 13 recently recently RB cord-014597-66vd2mdu 1754 14 developed develop VBN cord-014597-66vd2mdu 1754 15 CRISPR CRISPR NNP cord-014597-66vd2mdu 1754 16 / / SYM cord-014597-66vd2mdu 1754 17 Cas9 Cas9 NNP cord-014597-66vd2mdu 1754 18 system system NN cord-014597-66vd2mdu 1754 19 which which WDT cord-014597-66vd2mdu 1754 20 does do VBZ cord-014597-66vd2mdu 1754 21 not not RB cord-014597-66vd2mdu 1754 22 require require VB cord-014597-66vd2mdu 1754 23 a a DT cord-014597-66vd2mdu 1754 24 reporter reporter NN cord-014597-66vd2mdu 1754 25 transcript transcript NN cord-014597-66vd2mdu 1754 26 . . . cord-014597-66vd2mdu 1755 1 This this DT cord-014597-66vd2mdu 1755 2 system system NN cord-014597-66vd2mdu 1755 3 consists consist VBZ cord-014597-66vd2mdu 1755 4 of of IN cord-014597-66vd2mdu 1755 5 two two CD cord-014597-66vd2mdu 1755 6 main main JJ cord-014597-66vd2mdu 1755 7 components component NNS cord-014597-66vd2mdu 1755 8 : : : cord-014597-66vd2mdu 1755 9 the the DT cord-014597-66vd2mdu 1755 10 single single JJ cord-014597-66vd2mdu 1755 11 guide guide NN cord-014597-66vd2mdu 1755 12 RNA RNA NNP cord-014597-66vd2mdu 1755 13 ( ( -LRB- cord-014597-66vd2mdu 1755 14 sgRNA sgRNA VBG cord-014597-66vd2mdu 1755 15 ) ) -RRB- cord-014597-66vd2mdu 1755 16 and and CC cord-014597-66vd2mdu 1755 17 an an DT cord-014597-66vd2mdu 1755 18 endonuclease endonuclease NN cord-014597-66vd2mdu 1755 19 ( ( -LRB- cord-014597-66vd2mdu 1755 20 Cas9 Cas9 NNP cord-014597-66vd2mdu 1755 21 ) ) -RRB- cord-014597-66vd2mdu 1755 22 which which WDT cord-014597-66vd2mdu 1755 23 induces induce VBZ cord-014597-66vd2mdu 1755 24 double double JJ cord-014597-66vd2mdu 1755 25 strand strand NN cord-014597-66vd2mdu 1755 26 breaks break NNS cord-014597-66vd2mdu 1755 27 ( ( -LRB- cord-014597-66vd2mdu 1755 28 DSBs dsb NNS cord-014597-66vd2mdu 1755 29 ) ) -RRB- cord-014597-66vd2mdu 1755 30 . . . cord-014597-66vd2mdu 1756 1 These these DT cord-014597-66vd2mdu 1756 2 DSBs dsb NNS cord-014597-66vd2mdu 1756 3 can can MD cord-014597-66vd2mdu 1756 4 result result VB cord-014597-66vd2mdu 1756 5 in in IN cord-014597-66vd2mdu 1756 6 insertion insertion NN cord-014597-66vd2mdu 1756 7 or or CC cord-014597-66vd2mdu 1756 8 deletion deletion NN cord-014597-66vd2mdu 1756 9 ( ( -LRB- cord-014597-66vd2mdu 1756 10 indels indel NNS cord-014597-66vd2mdu 1756 11 ) ) -RRB- cord-014597-66vd2mdu 1756 12 of of IN cord-014597-66vd2mdu 1756 13 base base NN cord-014597-66vd2mdu 1756 14 pairs pair NNS cord-014597-66vd2mdu 1756 15 which which WDT cord-014597-66vd2mdu 1756 16 can can MD cord-014597-66vd2mdu 1756 17 disrupt disrupt VB cord-014597-66vd2mdu 1756 18 miRNA miRNA NNP cord-014597-66vd2mdu 1756 19 function function NN cord-014597-66vd2mdu 1756 20 and and CC cord-014597-66vd2mdu 1756 21 processing processing NN cord-014597-66vd2mdu 1756 22 [ [ -LRB- cord-014597-66vd2mdu 1756 23 3 3 CD cord-014597-66vd2mdu 1756 24 ] ] -RRB- cord-014597-66vd2mdu 1756 25 . . . cord-014597-66vd2mdu 1757 1 A a DT cord-014597-66vd2mdu 1757 2 CHO CHO NNP cord-014597-66vd2mdu 1757 3 - - HYPH cord-014597-66vd2mdu 1757 4 K1 K1 NNP cord-014597-66vd2mdu 1757 5 cell cell NN cord-014597-66vd2mdu 1757 6 line line NN cord-014597-66vd2mdu 1757 7 stably stably RB cord-014597-66vd2mdu 1757 8 expressing express VBG cord-014597-66vd2mdu 1757 9 an an DT cord-014597-66vd2mdu 1757 10 IgG igg NN cord-014597-66vd2mdu 1757 11 was be VBD cord-014597-66vd2mdu 1757 12 used use VBN cord-014597-66vd2mdu 1757 13 for for IN cord-014597-66vd2mdu 1757 14 knockdown knockdown NN cord-014597-66vd2mdu 1757 15 experiments experiment NNS cord-014597-66vd2mdu 1757 16 . . . cord-014597-66vd2mdu 1758 1 SgRNAs sgrna NNS cord-014597-66vd2mdu 1758 2 were be VBD cord-014597-66vd2mdu 1758 3 designed design VBN cord-014597-66vd2mdu 1758 4 to to TO cord-014597-66vd2mdu 1758 5 target target VB cord-014597-66vd2mdu 1758 6 the the DT cord-014597-66vd2mdu 1758 7 seed seed NN cord-014597-66vd2mdu 1758 8 region region NN cord-014597-66vd2mdu 1758 9 of of IN cord-014597-66vd2mdu 1758 10 each each DT cord-014597-66vd2mdu 1758 11 miRNA miRNA NNP cord-014597-66vd2mdu 1758 12 member member NN cord-014597-66vd2mdu 1758 13 and and CC cord-014597-66vd2mdu 1758 14 stable stable JJ cord-014597-66vd2mdu 1758 15 mixed mixed JJ cord-014597-66vd2mdu 1758 16 populations population NNS cord-014597-66vd2mdu 1758 17 were be VBD cord-014597-66vd2mdu 1758 18 generated generate VBN cord-014597-66vd2mdu 1758 19 ( ( -LRB- cord-014597-66vd2mdu 1758 20 Fig Fig NNP cord-014597-66vd2mdu 1758 21 . . . cord-014597-66vd2mdu 1758 22 1a 1a CD cord-014597-66vd2mdu 1758 23 ) ) -RRB- cord-014597-66vd2mdu 1758 24 . . . cord-014597-66vd2mdu 1759 1 Total total JJ cord-014597-66vd2mdu 1759 2 RNA RNA NNP cord-014597-66vd2mdu 1759 3 form form NN cord-014597-66vd2mdu 1759 4 each each DT cord-014597-66vd2mdu 1759 5 mixed mixed JJ cord-014597-66vd2mdu 1759 6 population population NN cord-014597-66vd2mdu 1759 7 was be VBD cord-014597-66vd2mdu 1759 8 reverse reverse RB cord-014597-66vd2mdu 1759 9 transcribed transcribe VBN cord-014597-66vd2mdu 1759 10 into into IN cord-014597-66vd2mdu 1759 11 cDNA cdna NN cord-014597-66vd2mdu 1759 12 using use VBG cord-014597-66vd2mdu 1759 13 miRNA miRNA NNP cord-014597-66vd2mdu 1759 14 specific specific JJ cord-014597-66vd2mdu 1759 15 stemloop stemloop JJ cord-014597-66vd2mdu 1759 16 primers primer NNS cord-014597-66vd2mdu 1759 17 . . . cord-014597-66vd2mdu 1760 1 The the DT cord-014597-66vd2mdu 1760 2 expression expression NN cord-014597-66vd2mdu 1760 3 was be VBD cord-014597-66vd2mdu 1760 4 quantified quantify VBN cord-014597-66vd2mdu 1760 5 by by IN cord-014597-66vd2mdu 1760 6 RT RT NNP cord-014597-66vd2mdu 1760 7 - - HYPH cord-014597-66vd2mdu 1760 8 qPCR qPCR NNP cord-014597-66vd2mdu 1760 9 . . . cord-014597-66vd2mdu 1761 1 To to TO cord-014597-66vd2mdu 1761 2 further further RB cord-014597-66vd2mdu 1761 3 analyse analyse VB cord-014597-66vd2mdu 1761 4 the the DT cord-014597-66vd2mdu 1761 5 range range NN cord-014597-66vd2mdu 1761 6 of of IN cord-014597-66vd2mdu 1761 7 indels indel NNS cord-014597-66vd2mdu 1762 1 the the DT cord-014597-66vd2mdu 1762 2 miR-23a miR-23a NNP cord-014597-66vd2mdu 1762 3 and and CC cord-014597-66vd2mdu 1762 4 miR-23b miR-23b NNP cord-014597-66vd2mdu 1762 5 clusters cluster NNS cord-014597-66vd2mdu 1762 6 were be VBD cord-014597-66vd2mdu 1762 7 amplified amplify VBN cord-014597-66vd2mdu 1762 8 by by IN cord-014597-66vd2mdu 1762 9 a a DT cord-014597-66vd2mdu 1762 10 standard standard JJ cord-014597-66vd2mdu 1762 11 high high JJ cord-014597-66vd2mdu 1762 12 - - HYPH cord-014597-66vd2mdu 1762 13 fidelity fidelity NN cord-014597-66vd2mdu 1762 14 PCR PCR NNP cord-014597-66vd2mdu 1762 15 . . . cord-014597-66vd2mdu 1763 1 Amplicons amplicon NNS cord-014597-66vd2mdu 1763 2 were be VBD cord-014597-66vd2mdu 1763 3 cloned clone VBN cord-014597-66vd2mdu 1763 4 into into IN cord-014597-66vd2mdu 1763 5 pCR pCR NNP cord-014597-66vd2mdu 1763 6 TM TM NNP cord-014597-66vd2mdu 1763 7 -TOPO -TOPO . cord-014597-66vd2mdu 1764 1 ® ® LS cord-014597-66vd2mdu 1764 2 vector vector NN cord-014597-66vd2mdu 1764 3 and and CC cord-014597-66vd2mdu 1764 4 positive positive JJ cord-014597-66vd2mdu 1764 5 clones clone NNS cord-014597-66vd2mdu 1764 6 were be VBD cord-014597-66vd2mdu 1764 7 analysed analyse VBN cord-014597-66vd2mdu 1764 8 by by IN cord-014597-66vd2mdu 1764 9 Sanger Sanger NNP cord-014597-66vd2mdu 1764 10 sequencing sequencing NN cord-014597-66vd2mdu 1764 11 . . . cord-014597-66vd2mdu 1765 1 Cell cell NN cord-014597-66vd2mdu 1765 2 growth growth NN cord-014597-66vd2mdu 1765 3 was be VBD cord-014597-66vd2mdu 1765 4 monitored monitor VBN cord-014597-66vd2mdu 1765 5 using use VBG cord-014597-66vd2mdu 1765 6 ViaCount ViaCount NNP cord-014597-66vd2mdu 1765 7 TM TM NNP cord-014597-66vd2mdu 1765 8 viability viability NN cord-014597-66vd2mdu 1765 9 stain stain NN cord-014597-66vd2mdu 1765 10 on on IN cord-014597-66vd2mdu 1765 11 a a DT cord-014597-66vd2mdu 1765 12 Guava Guava NNP cord-014597-66vd2mdu 1765 13 TM TM NNP cord-014597-66vd2mdu 1765 14 benchtop benchtop NN cord-014597-66vd2mdu 1765 15 flow flow NN cord-014597-66vd2mdu 1765 16 cytometer cytometer NN cord-014597-66vd2mdu 1765 17 . . . cord-014597-66vd2mdu 1766 1 Productivity productivity NN cord-014597-66vd2mdu 1766 2 was be VBD cord-014597-66vd2mdu 1766 3 assessed assess VBN cord-014597-66vd2mdu 1766 4 by by IN cord-014597-66vd2mdu 1766 5 ELISA ELISA NNP cord-014597-66vd2mdu 1766 6 . . . cord-014597-66vd2mdu 1767 1 Students student NNS cord-014597-66vd2mdu 1767 2 t t NN cord-014597-66vd2mdu 1767 3 - - HYPH cord-014597-66vd2mdu 1767 4 test test NN cord-014597-66vd2mdu 1767 5 was be VBD cord-014597-66vd2mdu 1767 6 used use VBN cord-014597-66vd2mdu 1767 7 for for IN cord-014597-66vd2mdu 1767 8 statistical statistical JJ cord-014597-66vd2mdu 1767 9 analysis analysis NN cord-014597-66vd2mdu 1767 10 . . . cord-014597-66vd2mdu 1768 1 It -PRON- PRP cord-014597-66vd2mdu 1768 2 was be VBD cord-014597-66vd2mdu 1768 3 shown show VBN cord-014597-66vd2mdu 1768 4 that that IN cord-014597-66vd2mdu 1768 5 miRNA miRNA NNP cord-014597-66vd2mdu 1768 6 expression expression NN cord-014597-66vd2mdu 1768 7 was be VBD cord-014597-66vd2mdu 1768 8 significantly significantly RB cord-014597-66vd2mdu 1768 9 reduced reduce VBN cord-014597-66vd2mdu 1768 10 in in IN cord-014597-66vd2mdu 1768 11 mixed mixed JJ cord-014597-66vd2mdu 1768 12 populations population NNS cord-014597-66vd2mdu 1768 13 . . . cord-014597-66vd2mdu 1769 1 A a DT cord-014597-66vd2mdu 1769 2 knockdown knockdown NN cord-014597-66vd2mdu 1769 3 up up IN cord-014597-66vd2mdu 1769 4 to to TO cord-014597-66vd2mdu 1769 5 95 95 CD cord-014597-66vd2mdu 1769 6 % % NN cord-014597-66vd2mdu 1769 7 was be VBD cord-014597-66vd2mdu 1769 8 achieved achieve VBN cord-014597-66vd2mdu 1769 9 for for IN cord-014597-66vd2mdu 1769 10 miR-23a miR-23a NNP cord-014597-66vd2mdu 1769 11 , , , cord-014597-66vd2mdu 1769 12 miR-23b miR-23b NNP cord-014597-66vd2mdu 1769 13 and and CC cord-014597-66vd2mdu 1769 14 miR-24 miR-24 VBD cord-014597-66vd2mdu 1769 15 . . . cord-014597-66vd2mdu 1770 1 The the DT cord-014597-66vd2mdu 1770 2 knockdown knockdown NN cord-014597-66vd2mdu 1770 3 in in IN cord-014597-66vd2mdu 1770 4 miR-27a miR-27a NNP cord-014597-66vd2mdu 1770 5 and and CC cord-014597-66vd2mdu 1770 6 miR-27b miR-27b NNP cord-014597-66vd2mdu 1770 7 expression expression NN cord-014597-66vd2mdu 1770 8 was be VBD cord-014597-66vd2mdu 1770 9 considerably considerably RB cord-014597-66vd2mdu 1770 10 less less JJR cord-014597-66vd2mdu 1770 11 -between -between $ cord-014597-66vd2mdu 1770 12 70 70 CD cord-014597-66vd2mdu 1770 13 - - SYM cord-014597-66vd2mdu 1770 14 90 90 CD cord-014597-66vd2mdu 1770 15 % % NN cord-014597-66vd2mdu 1770 16 ( ( -LRB- cord-014597-66vd2mdu 1770 17 n=3 n=3 NN cord-014597-66vd2mdu 1770 18 , , , cord-014597-66vd2mdu 1770 19 * * NFP cord-014597-66vd2mdu 1770 20 P p NN cord-014597-66vd2mdu 1770 21 ≤ ≤ NN cord-014597-66vd2mdu 1770 22 0.05 0.05 CD cord-014597-66vd2mdu 1770 23 , , , cord-014597-66vd2mdu 1771 1 * * NFP cord-014597-66vd2mdu 1771 2 * * NFP cord-014597-66vd2mdu 1771 3 P p NN cord-014597-66vd2mdu 1771 4 ≤ ≤ NN cord-014597-66vd2mdu 1771 5 0.01 0.01 CD cord-014597-66vd2mdu 1771 6 , , , cord-014597-66vd2mdu 1772 1 * * NFP cord-014597-66vd2mdu 1772 2 * * NFP cord-014597-66vd2mdu 1772 3 * * NFP cord-014597-66vd2mdu 1772 4 P p NN cord-014597-66vd2mdu 1772 5 ≤ ≤ NN cord-014597-66vd2mdu 1772 6 0.001 0.001 CD cord-014597-66vd2mdu 1772 7 ) ) -RRB- cord-014597-66vd2mdu 1773 1 ( ( -LRB- cord-014597-66vd2mdu 1773 2 Fig Fig NNP cord-014597-66vd2mdu 1773 3 . . . cord-014597-66vd2mdu 1773 4 1b 1b CD cord-014597-66vd2mdu 1773 5 ) ) -RRB- cord-014597-66vd2mdu 1773 6 . . . cord-014597-66vd2mdu 1774 1 Furthermore furthermore RB cord-014597-66vd2mdu 1774 2 , , , cord-014597-66vd2mdu 1774 3 it -PRON- PRP cord-014597-66vd2mdu 1774 4 was be VBD cord-014597-66vd2mdu 1774 5 shown show VBN cord-014597-66vd2mdu 1774 6 that that IN cord-014597-66vd2mdu 1774 7 various various JJ cord-014597-66vd2mdu 1774 8 sizes size NNS cord-014597-66vd2mdu 1774 9 of of IN cord-014597-66vd2mdu 1774 10 indels indel NNS cord-014597-66vd2mdu 1774 11 were be VBD cord-014597-66vd2mdu 1774 12 generated generate VBN cord-014597-66vd2mdu 1774 13 by by IN cord-014597-66vd2mdu 1774 14 targeting target VBG cord-014597-66vd2mdu 1774 15 the the DT cord-014597-66vd2mdu 1774 16 seed seed NN cord-014597-66vd2mdu 1774 17 region region NN cord-014597-66vd2mdu 1774 18 . . . cord-014597-66vd2mdu 1775 1 Smaller small JJR cord-014597-66vd2mdu 1775 2 indels indel NNS cord-014597-66vd2mdu 1775 3 ( ( -LRB- cord-014597-66vd2mdu 1775 4 +1/ +1/ NNP cord-014597-66vd2mdu 1775 5 +2/-1/-2 +2/-1/-2 NNP cord-014597-66vd2mdu 1775 6 bps bp NNS cord-014597-66vd2mdu 1775 7 ) ) -RRB- cord-014597-66vd2mdu 1775 8 seemed seem VBD cord-014597-66vd2mdu 1775 9 to to TO cord-014597-66vd2mdu 1775 10 be be VB cord-014597-66vd2mdu 1775 11 more more RBR cord-014597-66vd2mdu 1775 12 common common JJ cord-014597-66vd2mdu 1775 13 but but CC cord-014597-66vd2mdu 1775 14 larger large JJR cord-014597-66vd2mdu 1775 15 deletions deletion NNS cord-014597-66vd2mdu 1775 16 were be VBD cord-014597-66vd2mdu 1775 17 detected detect VBN cord-014597-66vd2mdu 1775 18 as as RB cord-014597-66vd2mdu 1775 19 well well RB cord-014597-66vd2mdu 1776 1 ( ( -LRB- cord-014597-66vd2mdu 1776 2 Fig Fig NNP cord-014597-66vd2mdu 1776 3 . . . cord-014597-66vd2mdu 1776 4 1c 1c CD cord-014597-66vd2mdu 1776 5 ) ) -RRB- cord-014597-66vd2mdu 1776 6 . . . cord-014597-66vd2mdu 1777 1 MiR-23a MiR-23a NNP cord-014597-66vd2mdu 1777 2 , , , cord-014597-66vd2mdu 1777 3 miR-23b miR-23b NNP cord-014597-66vd2mdu 1777 4 and and CC cord-014597-66vd2mdu 1777 5 miR-27b miR-27b NNP cord-014597-66vd2mdu 1777 6 showed show VBD cord-014597-66vd2mdu 1777 7 increased increased JJ cord-014597-66vd2mdu 1777 8 viability viability NN cord-014597-66vd2mdu 1777 9 in in IN cord-014597-66vd2mdu 1777 10 late late JJ cord-014597-66vd2mdu 1777 11 stages stage NNS cord-014597-66vd2mdu 1777 12 of of IN cord-014597-66vd2mdu 1777 13 the the DT cord-014597-66vd2mdu 1777 14 culture culture NN cord-014597-66vd2mdu 1777 15 . . . cord-014597-66vd2mdu 1778 1 Depletion depletion NN cord-014597-66vd2mdu 1778 2 of of IN cord-014597-66vd2mdu 1778 3 miR-27a miR-27a NNP cord-014597-66vd2mdu 1778 4 reduced reduce VBN cord-014597-66vd2mdu 1778 5 growth growth NN cord-014597-66vd2mdu 1778 6 significantly significantly RB cord-014597-66vd2mdu 1778 7 whereas whereas IN cord-014597-66vd2mdu 1778 8 knockdown knockdown NN cord-014597-66vd2mdu 1778 9 of of IN cord-014597-66vd2mdu 1778 10 miR-24 mir-24 CC cord-014597-66vd2mdu 1778 11 showed show VBD cord-014597-66vd2mdu 1778 12 increased increase VBN cord-014597-66vd2mdu 1778 13 proliferation proliferation NN cord-014597-66vd2mdu 1778 14 as as RB cord-014597-66vd2mdu 1778 15 well well RB cord-014597-66vd2mdu 1778 16 as as IN cord-014597-66vd2mdu 1778 17 boosting boost VBG cord-014597-66vd2mdu 1778 18 IgG igg NN cord-014597-66vd2mdu 1778 19 titers titer NNS cord-014597-66vd2mdu 1778 20 ( ( -LRB- cord-014597-66vd2mdu 1778 21 Table Table NNP cord-014597-66vd2mdu 1778 22 1 1 CD cord-014597-66vd2mdu 1778 23 ) ) -RRB- cord-014597-66vd2mdu 1778 24 . . . cord-014597-66vd2mdu 1779 1 In in IN cord-014597-66vd2mdu 1779 2 this this DT cord-014597-66vd2mdu 1779 3 work work NN cord-014597-66vd2mdu 1779 4 , , , cord-014597-66vd2mdu 1779 5 we -PRON- PRP cord-014597-66vd2mdu 1779 6 have have VBP cord-014597-66vd2mdu 1779 7 shown show VBN cord-014597-66vd2mdu 1779 8 that that IN cord-014597-66vd2mdu 1779 9 CRISPR CRISPR NNP cord-014597-66vd2mdu 1779 10 / / SYM cord-014597-66vd2mdu 1779 11 Cas9 Cas9 NNP cord-014597-66vd2mdu 1779 12 can can MD cord-014597-66vd2mdu 1779 13 be be VB cord-014597-66vd2mdu 1779 14 successfully successfully RB cord-014597-66vd2mdu 1779 15 applied apply VBN cord-014597-66vd2mdu 1779 16 as as IN cord-014597-66vd2mdu 1779 17 a a DT cord-014597-66vd2mdu 1779 18 tool tool NN cord-014597-66vd2mdu 1779 19 to to TO cord-014597-66vd2mdu 1779 20 knockdown knockdown VB cord-014597-66vd2mdu 1779 21 miRNA miRNA NNP cord-014597-66vd2mdu 1779 22 expression expression NN cord-014597-66vd2mdu 1779 23 in in IN cord-014597-66vd2mdu 1779 24 CHO CHO NNP cord-014597-66vd2mdu 1779 25 cells cell NNS cord-014597-66vd2mdu 1779 26 . . . cord-014597-66vd2mdu 1780 1 The the DT cord-014597-66vd2mdu 1780 2 data datum NNS cord-014597-66vd2mdu 1780 3 was be VBD cord-014597-66vd2mdu 1780 4 generated generate VBN cord-014597-66vd2mdu 1780 5 using use VBG cord-014597-66vd2mdu 1780 6 mixed mixed JJ cord-014597-66vd2mdu 1780 7 pools pool NNS cord-014597-66vd2mdu 1780 8 and and CC cord-014597-66vd2mdu 1780 9 it -PRON- PRP cord-014597-66vd2mdu 1780 10 remains remain VBZ cord-014597-66vd2mdu 1780 11 to to TO cord-014597-66vd2mdu 1780 12 be be VB cord-014597-66vd2mdu 1780 13 established establish VBN cord-014597-66vd2mdu 1780 14 if if IN cord-014597-66vd2mdu 1780 15 both both DT cord-014597-66vd2mdu 1780 16 alleles allele NNS cord-014597-66vd2mdu 1780 17 can can MD cord-014597-66vd2mdu 1780 18 be be VB cord-014597-66vd2mdu 1780 19 successfully successfully RB cord-014597-66vd2mdu 1780 20 targeted target VBN cord-014597-66vd2mdu 1780 21 e.g. e.g. RB cord-014597-66vd2mdu 1780 22 using use VBG cord-014597-66vd2mdu 1780 23 nextgeneration nextgeneration NN cord-014597-66vd2mdu 1780 24 sequencing sequencing NN cord-014597-66vd2mdu 1780 25 of of IN cord-014597-66vd2mdu 1780 26 individual individual JJ cord-014597-66vd2mdu 1780 27 clones clone NNS cord-014597-66vd2mdu 1780 28 . . . cord-014597-66vd2mdu 1781 1 Background background NN cord-014597-66vd2mdu 1781 2 Chinese chinese JJ cord-014597-66vd2mdu 1781 3 hamster hamster NN cord-014597-66vd2mdu 1781 4 ovary ovary NN cord-014597-66vd2mdu 1781 5 ( ( -LRB- cord-014597-66vd2mdu 1781 6 CHO CHO NNP cord-014597-66vd2mdu 1781 7 ) ) -RRB- cord-014597-66vd2mdu 1781 8 cells cell NNS cord-014597-66vd2mdu 1781 9 are be VBP cord-014597-66vd2mdu 1781 10 the the DT cord-014597-66vd2mdu 1781 11 most most RBS cord-014597-66vd2mdu 1781 12 widely widely RB cord-014597-66vd2mdu 1781 13 used use VBN cord-014597-66vd2mdu 1781 14 host host NN cord-014597-66vd2mdu 1781 15 cell cell NN cord-014597-66vd2mdu 1781 16 line line NN cord-014597-66vd2mdu 1781 17 for for IN cord-014597-66vd2mdu 1781 18 the the DT cord-014597-66vd2mdu 1781 19 production production NN cord-014597-66vd2mdu 1781 20 of of IN cord-014597-66vd2mdu 1781 21 therapeutic therapeutic JJ cord-014597-66vd2mdu 1781 22 antibodies antibody NNS cord-014597-66vd2mdu 1781 23 . . . cord-014597-66vd2mdu 1782 1 Pre pre JJ cord-014597-66vd2mdu 1782 2 - - JJ cord-014597-66vd2mdu 1782 3 and and CC cord-014597-66vd2mdu 1782 4 posttranslational posttranslational JJ cord-014597-66vd2mdu 1782 5 modifications modification NNS cord-014597-66vd2mdu 1782 6 and and CC cord-014597-66vd2mdu 1782 7 optimization optimization NN cord-014597-66vd2mdu 1782 8 of of IN cord-014597-66vd2mdu 1782 9 culture culture NN cord-014597-66vd2mdu 1782 10 methods method NNS cord-014597-66vd2mdu 1782 11 contributed contribute VBD cord-014597-66vd2mdu 1782 12 to to TO cord-014597-66vd2mdu 1782 13 increase increase VB cord-014597-66vd2mdu 1782 14 the the DT cord-014597-66vd2mdu 1782 15 productivity productivity NN cord-014597-66vd2mdu 1782 16 , , , cord-014597-66vd2mdu 1782 17 resulting result VBG cord-014597-66vd2mdu 1782 18 in in IN cord-014597-66vd2mdu 1782 19 a a DT cord-014597-66vd2mdu 1782 20 very very RB cord-014597-66vd2mdu 1782 21 high high JJ cord-014597-66vd2mdu 1782 22 titre titre NN cord-014597-66vd2mdu 1782 23 [ [ -LRB- cord-014597-66vd2mdu 1782 24 1 1 CD cord-014597-66vd2mdu 1782 25 , , , cord-014597-66vd2mdu 1782 26 2 2 CD cord-014597-66vd2mdu 1782 27 ] ] -RRB- cord-014597-66vd2mdu 1782 28 . . . cord-014597-66vd2mdu 1783 1 However however RB cord-014597-66vd2mdu 1783 2 , , , cord-014597-66vd2mdu 1783 3 it -PRON- PRP cord-014597-66vd2mdu 1783 4 has have VBZ cord-014597-66vd2mdu 1783 5 been be VBN cord-014597-66vd2mdu 1783 6 pointed point VBN cord-014597-66vd2mdu 1783 7 out out RP cord-014597-66vd2mdu 1783 8 that that IN cord-014597-66vd2mdu 1783 9 the the DT cord-014597-66vd2mdu 1783 10 intracellular intracellular JJ cord-014597-66vd2mdu 1783 11 secretion secretion NN cord-014597-66vd2mdu 1783 12 process process NN cord-014597-66vd2mdu 1783 13 is be VBZ cord-014597-66vd2mdu 1783 14 a a DT cord-014597-66vd2mdu 1783 15 bottleneck bottleneck NN cord-014597-66vd2mdu 1783 16 in in IN cord-014597-66vd2mdu 1783 17 the the DT cord-014597-66vd2mdu 1783 18 production production NN cord-014597-66vd2mdu 1783 19 of of IN cord-014597-66vd2mdu 1783 20 therapeutic therapeutic JJ cord-014597-66vd2mdu 1783 21 antibodies antibody NNS cord-014597-66vd2mdu 1783 22 [ [ -LRB- cord-014597-66vd2mdu 1783 23 3 3 CD cord-014597-66vd2mdu 1783 24 ] ] -RRB- cord-014597-66vd2mdu 1783 25 . . . cord-014597-66vd2mdu 1784 1 In in IN cord-014597-66vd2mdu 1784 2 addition addition NN cord-014597-66vd2mdu 1784 3 , , , cord-014597-66vd2mdu 1784 4 the the DT cord-014597-66vd2mdu 1784 5 details detail NNS cord-014597-66vd2mdu 1784 6 of of IN cord-014597-66vd2mdu 1784 7 the the DT cord-014597-66vd2mdu 1784 8 process process NN cord-014597-66vd2mdu 1784 9 of of IN cord-014597-66vd2mdu 1784 10 secretion secretion NN cord-014597-66vd2mdu 1784 11 of of IN cord-014597-66vd2mdu 1784 12 humanized humanize VBN cord-014597-66vd2mdu 1784 13 recombinant recombinant JJ cord-014597-66vd2mdu 1784 14 antibodies antibody NNS cord-014597-66vd2mdu 1784 15 from from IN cord-014597-66vd2mdu 1784 16 CHO CHO NNP cord-014597-66vd2mdu 1784 17 cells cell NNS cord-014597-66vd2mdu 1784 18 have have VBP cord-014597-66vd2mdu 1784 19 not not RB cord-014597-66vd2mdu 1784 20 been be VBN cord-014597-66vd2mdu 1784 21 well well RB cord-014597-66vd2mdu 1784 22 investigated investigate VBN cord-014597-66vd2mdu 1784 23 . . . cord-014597-66vd2mdu 1785 1 In in IN cord-014597-66vd2mdu 1785 2 this this DT cord-014597-66vd2mdu 1785 3 study study NN cord-014597-66vd2mdu 1785 4 , , , cord-014597-66vd2mdu 1785 5 we -PRON- PRP cord-014597-66vd2mdu 1785 6 thus thus RB cord-014597-66vd2mdu 1785 7 analysed analyse VBD cord-014597-66vd2mdu 1785 8 the the DT cord-014597-66vd2mdu 1785 9 detailed detailed JJ cord-014597-66vd2mdu 1785 10 process process NN cord-014597-66vd2mdu 1785 11 of of IN cord-014597-66vd2mdu 1785 12 secretion secretion NN cord-014597-66vd2mdu 1785 13 of of IN cord-014597-66vd2mdu 1785 14 therapeutic therapeutic JJ cord-014597-66vd2mdu 1785 15 antibodies antibody NNS cord-014597-66vd2mdu 1785 16 using use VBG cord-014597-66vd2mdu 1785 17 CHO CHO NNP cord-014597-66vd2mdu 1785 18 cell cell NN cord-014597-66vd2mdu 1785 19 lines line NNS cord-014597-66vd2mdu 1785 20 , , , cord-014597-66vd2mdu 1785 21 which which WDT cord-014597-66vd2mdu 1785 22 have have VBP cord-014597-66vd2mdu 1785 23 already already RB cord-014597-66vd2mdu 1785 24 been be VBN cord-014597-66vd2mdu 1785 25 established establish VBN cord-014597-66vd2mdu 1785 26 as as IN cord-014597-66vd2mdu 1785 27 high high JJ cord-014597-66vd2mdu 1785 28 producers producer NNS cord-014597-66vd2mdu 1785 29 , , , cord-014597-66vd2mdu 1785 30 with with IN cord-014597-66vd2mdu 1785 31 the the DT cord-014597-66vd2mdu 1785 32 aim aim NN cord-014597-66vd2mdu 1785 33 of of IN cord-014597-66vd2mdu 1785 34 obtaining obtain VBG cord-014597-66vd2mdu 1785 35 information information NN cord-014597-66vd2mdu 1785 36 for for IN cord-014597-66vd2mdu 1785 37 the the DT cord-014597-66vd2mdu 1785 38 more more RBR cord-014597-66vd2mdu 1785 39 rational rational JJ cord-014597-66vd2mdu 1785 40 and and CC cord-014597-66vd2mdu 1785 41 efficient efficient JJ cord-014597-66vd2mdu 1785 42 establishment establishment NN cord-014597-66vd2mdu 1785 43 of of IN cord-014597-66vd2mdu 1785 44 high high JJ cord-014597-66vd2mdu 1785 45 - - HYPH cord-014597-66vd2mdu 1785 46 producer producer NN cord-014597-66vd2mdu 1785 47 cells cell NNS cord-014597-66vd2mdu 1785 48 . . . cord-014597-66vd2mdu 1786 1 We -PRON- PRP cord-014597-66vd2mdu 1786 2 performed perform VBD cord-014597-66vd2mdu 1786 3 1 1 CD cord-014597-66vd2mdu 1786 4 ) ) -RRB- cord-014597-66vd2mdu 1786 5 chase chase NN cord-014597-66vd2mdu 1786 6 assay assay NN cord-014597-66vd2mdu 1786 7 , , , cord-014597-66vd2mdu 1786 8 2 2 CD cord-014597-66vd2mdu 1786 9 ) ) -RRB- cord-014597-66vd2mdu 1786 10 immunofluorescent immunofluorescent NNP cord-014597-66vd2mdu 1786 11 microscopy microscopy NNP cord-014597-66vd2mdu 1786 12 observation observation NN cord-014597-66vd2mdu 1786 13 , , , cord-014597-66vd2mdu 1786 14 and and CC cord-014597-66vd2mdu 1786 15 3 3 LS cord-014597-66vd2mdu 1786 16 ) ) -RRB- cord-014597-66vd2mdu 1786 17 size size NN cord-014597-66vd2mdu 1786 18 exclusion exclusion NN cord-014597-66vd2mdu 1786 19 chromatography chromatography NN cord-014597-66vd2mdu 1786 20 ( ( -LRB- cord-014597-66vd2mdu 1786 21 SEC SEC NNP cord-014597-66vd2mdu 1786 22 ) ) -RRB- cord-014597-66vd2mdu 1786 23 analysis analysis NN cord-014597-66vd2mdu 1786 24 to to TO cord-014597-66vd2mdu 1786 25 investigate investigate VB cord-014597-66vd2mdu 1786 26 the the DT cord-014597-66vd2mdu 1786 27 duration duration NN cord-014597-66vd2mdu 1786 28 of of IN cord-014597-66vd2mdu 1786 29 secretion secretion NN cord-014597-66vd2mdu 1786 30 , , , cord-014597-66vd2mdu 1786 31 bottleneck bottleneck NN cord-014597-66vd2mdu 1786 32 position position NN cord-014597-66vd2mdu 1786 33 , , , cord-014597-66vd2mdu 1786 34 and and CC cord-014597-66vd2mdu 1786 35 formation formation NN cord-014597-66vd2mdu 1786 36 of of IN cord-014597-66vd2mdu 1786 37 recombinant recombinant JJ cord-014597-66vd2mdu 1786 38 IgG IgG NNP cord-014597-66vd2mdu 1786 39 , , , cord-014597-66vd2mdu 1786 40 respectively respectively RB cord-014597-66vd2mdu 1786 41 . . . cord-014597-66vd2mdu 1787 1 High high JJ cord-014597-66vd2mdu 1787 2 - - HYPH cord-014597-66vd2mdu 1787 3 producer producer NN cord-014597-66vd2mdu 1787 4 CHO CHO NNP cord-014597-66vd2mdu 1787 5 cells cell NNS cord-014597-66vd2mdu 1787 6 expressing express VBG cord-014597-66vd2mdu 1787 7 humanized humanize VBN cord-014597-66vd2mdu 1787 8 IgG1 igg1 NN cord-014597-66vd2mdu 1788 1 [ [ -LRB- cord-014597-66vd2mdu 1788 2 4 4 CD cord-014597-66vd2mdu 1788 3 ] ] -RRB- cord-014597-66vd2mdu 1788 4 and and CC cord-014597-66vd2mdu 1788 5 IgG3 IgG3 NNP cord-014597-66vd2mdu 1788 6 were be VBD cord-014597-66vd2mdu 1788 7 used use VBN cord-014597-66vd2mdu 1788 8 . . . cord-014597-66vd2mdu 1789 1 For for IN cord-014597-66vd2mdu 1789 2 the the DT cord-014597-66vd2mdu 1789 3 chase chase NN cord-014597-66vd2mdu 1789 4 assay assay NN cord-014597-66vd2mdu 1789 5 , , , cord-014597-66vd2mdu 1789 6 cells cell NNS cord-014597-66vd2mdu 1789 7 were be VBD cord-014597-66vd2mdu 1789 8 cultivated cultivate VBN cord-014597-66vd2mdu 1789 9 in in IN cord-014597-66vd2mdu 1789 10 shake shake NN cord-014597-66vd2mdu 1789 11 flasks flask NNS cord-014597-66vd2mdu 1789 12 with with IN cord-014597-66vd2mdu 1789 13 serum serum NN cord-014597-66vd2mdu 1789 14 - - HYPH cord-014597-66vd2mdu 1789 15 free free JJ cord-014597-66vd2mdu 1789 16 medium medium NN cord-014597-66vd2mdu 1789 17 containing contain VBG cord-014597-66vd2mdu 1789 18 50 50 CD cord-014597-66vd2mdu 1789 19 μg μg NNS cord-014597-66vd2mdu 1789 20 / / SYM cord-014597-66vd2mdu 1789 21 ml ml NN cord-014597-66vd2mdu 1789 22 cycloheximide cycloheximide NN cord-014597-66vd2mdu 1789 23 ( ( -LRB- cord-014597-66vd2mdu 1789 24 CHX CHX NNP cord-014597-66vd2mdu 1789 25 ) ) -RRB- cord-014597-66vd2mdu 1789 26 to to TO cord-014597-66vd2mdu 1789 27 stop stop VB cord-014597-66vd2mdu 1789 28 nascent nascent JJ cord-014597-66vd2mdu 1789 29 peptide peptide NN cord-014597-66vd2mdu 1789 30 synthesis synthesis NN cord-014597-66vd2mdu 1789 31 . . . cord-014597-66vd2mdu 1790 1 The the DT cord-014597-66vd2mdu 1790 2 amounts amount NNS cord-014597-66vd2mdu 1790 3 of of IN cord-014597-66vd2mdu 1790 4 IgG igg NN cord-014597-66vd2mdu 1790 5 both both DT cord-014597-66vd2mdu 1790 6 remaining remain VBG cord-014597-66vd2mdu 1790 7 in in IN cord-014597-66vd2mdu 1790 8 the the DT cord-014597-66vd2mdu 1790 9 cell cell NN cord-014597-66vd2mdu 1790 10 and and CC cord-014597-66vd2mdu 1790 11 secreted secrete VBD cord-014597-66vd2mdu 1790 12 into into IN cord-014597-66vd2mdu 1790 13 the the DT cord-014597-66vd2mdu 1790 14 medium medium NN cord-014597-66vd2mdu 1790 15 at at IN cord-014597-66vd2mdu 1790 16 each each DT cord-014597-66vd2mdu 1790 17 time time NN cord-014597-66vd2mdu 1790 18 point point NN cord-014597-66vd2mdu 1790 19 were be VBD cord-014597-66vd2mdu 1790 20 measured measure VBN cord-014597-66vd2mdu 1790 21 by by IN cord-014597-66vd2mdu 1790 22 quantitative quantitative JJ cord-014597-66vd2mdu 1790 23 western western JJ cord-014597-66vd2mdu 1790 24 blotting blotting NN cord-014597-66vd2mdu 1790 25 . . . cord-014597-66vd2mdu 1791 1 For for IN cord-014597-66vd2mdu 1791 2 immunofluorescent immunofluorescent NNP cord-014597-66vd2mdu 1791 3 microscopy microscopy NNP cord-014597-66vd2mdu 1791 4 observation observation NN cord-014597-66vd2mdu 1791 5 , , , cord-014597-66vd2mdu 1791 6 cells cell NNS cord-014597-66vd2mdu 1791 7 were be VBD cord-014597-66vd2mdu 1791 8 cultivated cultivate VBN cord-014597-66vd2mdu 1791 9 on on IN cord-014597-66vd2mdu 1791 10 coverslips coverslip NNS cord-014597-66vd2mdu 1791 11 with with IN cord-014597-66vd2mdu 1791 12 CHX CHX NNP cord-014597-66vd2mdu 1791 13 for for IN cord-014597-66vd2mdu 1791 14 4 4 CD cord-014597-66vd2mdu 1791 15 h. h. NNP cord-014597-66vd2mdu 1791 16 Immunofluorescent Immunofluorescent NNP cord-014597-66vd2mdu 1791 17 staining stain VBG cord-014597-66vd2mdu 1791 18 against against IN cord-014597-66vd2mdu 1791 19 the the DT cord-014597-66vd2mdu 1791 20 recombinant recombinant JJ cord-014597-66vd2mdu 1791 21 IgG igg NN cord-014597-66vd2mdu 1791 22 , , , cord-014597-66vd2mdu 1791 23 endoplasmic endoplasmic NN cord-014597-66vd2mdu 1791 24 reticulum reticulum NN cord-014597-66vd2mdu 1791 25 ( ( -LRB- cord-014597-66vd2mdu 1791 26 ER ER NNP cord-014597-66vd2mdu 1791 27 ) ) -RRB- cord-014597-66vd2mdu 1791 28 , , , cord-014597-66vd2mdu 1791 29 and and CC cord-014597-66vd2mdu 1791 30 Golgi Golgi NNP cord-014597-66vd2mdu 1791 31 apparatus apparatus NN cord-014597-66vd2mdu 1791 32 was be VBD cord-014597-66vd2mdu 1791 33 performed perform VBN cord-014597-66vd2mdu 1791 34 after after IN cord-014597-66vd2mdu 1791 35 chemical chemical JJ cord-014597-66vd2mdu 1791 36 fixation fixation NN cord-014597-66vd2mdu 1791 37 . . . cord-014597-66vd2mdu 1792 1 For for IN cord-014597-66vd2mdu 1792 2 SEC SEC NNP cord-014597-66vd2mdu 1792 3 , , , cord-014597-66vd2mdu 1792 4 cells cell NNS cord-014597-66vd2mdu 1792 5 cultured culture VBN cord-014597-66vd2mdu 1792 6 with with IN cord-014597-66vd2mdu 1792 7 CHX CHX NNP cord-014597-66vd2mdu 1792 8 were be VBD cord-014597-66vd2mdu 1792 9 re re VBN cord-014597-66vd2mdu 1792 10 - - VBN cord-014597-66vd2mdu 1792 11 suspended suspend VBN cord-014597-66vd2mdu 1792 12 in in IN cord-014597-66vd2mdu 1792 13 a a DT cord-014597-66vd2mdu 1792 14 buffer buffer NN cord-014597-66vd2mdu 1792 15 containing contain VBG cord-014597-66vd2mdu 1792 16 tritonX-100 tritonX-100 NNS cord-014597-66vd2mdu 1792 17 and and CC cord-014597-66vd2mdu 1792 18 injected inject VBD cord-014597-66vd2mdu 1792 19 into into IN cord-014597-66vd2mdu 1792 20 a a DT cord-014597-66vd2mdu 1792 21 column column NN cord-014597-66vd2mdu 1792 22 . . . cord-014597-66vd2mdu 1793 1 The the DT cord-014597-66vd2mdu 1793 2 amount amount NN cord-014597-66vd2mdu 1793 3 of of IN cord-014597-66vd2mdu 1793 4 IgG igg NN cord-014597-66vd2mdu 1793 5 in in IN cord-014597-66vd2mdu 1793 6 each each DT cord-014597-66vd2mdu 1793 7 fraction fraction NN cord-014597-66vd2mdu 1793 8 was be VBD cord-014597-66vd2mdu 1793 9 measured measure VBN cord-014597-66vd2mdu 1793 10 by by IN cord-014597-66vd2mdu 1793 11 quantitative quantitative JJ cord-014597-66vd2mdu 1793 12 western western JJ cord-014597-66vd2mdu 1793 13 blotting blotting NN cord-014597-66vd2mdu 1793 14 . . . cord-014597-66vd2mdu 1794 1 The the DT cord-014597-66vd2mdu 1794 2 amount amount NN cord-014597-66vd2mdu 1794 3 of of IN cord-014597-66vd2mdu 1794 4 IgG3 igg3 NN cord-014597-66vd2mdu 1794 5 in in IN cord-014597-66vd2mdu 1794 6 the the DT cord-014597-66vd2mdu 1794 7 supernatant supernatant NN cord-014597-66vd2mdu 1794 8 increased increase VBD cord-014597-66vd2mdu 1794 9 until until IN cord-014597-66vd2mdu 1794 10 4 4 CD cord-014597-66vd2mdu 1794 11 - - SYM cord-014597-66vd2mdu 1794 12 6 6 CD cord-014597-66vd2mdu 1794 13 h h NN cord-014597-66vd2mdu 1794 14 after after IN cord-014597-66vd2mdu 1794 15 the the DT cord-014597-66vd2mdu 1794 16 inhibition inhibition NN cord-014597-66vd2mdu 1794 17 of of IN cord-014597-66vd2mdu 1794 18 protein protein NN cord-014597-66vd2mdu 1794 19 synthesis synthesis NN cord-014597-66vd2mdu 1794 20 by by IN cord-014597-66vd2mdu 1794 21 CHX CHX NNP cord-014597-66vd2mdu 1794 22 ; ; : cord-014597-66vd2mdu 1794 23 however however RB cord-014597-66vd2mdu 1794 24 , , , cord-014597-66vd2mdu 1794 25 it -PRON- PRP cord-014597-66vd2mdu 1794 26 hardly hardly RB cord-014597-66vd2mdu 1794 27 changed change VBD cord-014597-66vd2mdu 1794 28 thereafter thereafter RB cord-014597-66vd2mdu 1795 1 ( ( -LRB- cord-014597-66vd2mdu 1795 2 Fig Fig NNP cord-014597-66vd2mdu 1795 3 . . NNP cord-014597-66vd2mdu 1795 4 1 1 CD cord-014597-66vd2mdu 1795 5 , , , cord-014597-66vd2mdu 1795 6 upper upper JJ cord-014597-66vd2mdu 1795 7 panel panel NN cord-014597-66vd2mdu 1795 8 ) ) -RRB- cord-014597-66vd2mdu 1795 9 . . . cord-014597-66vd2mdu 1796 1 At at IN cord-014597-66vd2mdu 1796 2 this this DT cord-014597-66vd2mdu 1796 3 point point NN cord-014597-66vd2mdu 1796 4 in in IN cord-014597-66vd2mdu 1796 5 time time NN cord-014597-66vd2mdu 1796 6 , , , cord-014597-66vd2mdu 1796 7 however however RB cord-014597-66vd2mdu 1796 8 , , , cord-014597-66vd2mdu 1796 9 around around RB cord-014597-66vd2mdu 1796 10 40 40 CD cord-014597-66vd2mdu 1796 11 % % NN cord-014597-66vd2mdu 1796 12 of of IN cord-014597-66vd2mdu 1796 13 IgG IgG NNP cord-014597-66vd2mdu 1796 14 still still RB cord-014597-66vd2mdu 1796 15 remained remain VBD cord-014597-66vd2mdu 1796 16 in in IN cord-014597-66vd2mdu 1796 17 the the DT cord-014597-66vd2mdu 1796 18 cells cell NNS cord-014597-66vd2mdu 1796 19 ( ( -LRB- cord-014597-66vd2mdu 1796 20 Fig Fig NNP cord-014597-66vd2mdu 1796 21 . . NNP cord-014597-66vd2mdu 1796 22 1 1 CD cord-014597-66vd2mdu 1796 23 , , , cord-014597-66vd2mdu 1796 24 lower low JJR cord-014597-66vd2mdu 1796 25 panel panel NN cord-014597-66vd2mdu 1796 26 ) ) -RRB- cord-014597-66vd2mdu 1796 27 , , , cord-014597-66vd2mdu 1796 28 meaning mean VBG cord-014597-66vd2mdu 1796 29 that that IN cord-014597-66vd2mdu 1796 30 all all DT cord-014597-66vd2mdu 1796 31 of of IN cord-014597-66vd2mdu 1796 32 the the DT cord-014597-66vd2mdu 1796 33 synthesized synthesize VBN cord-014597-66vd2mdu 1796 34 IgG igg NN cord-014597-66vd2mdu 1796 35 could could MD cord-014597-66vd2mdu 1796 36 not not RB cord-014597-66vd2mdu 1796 37 be be VB cord-014597-66vd2mdu 1796 38 secreted secrete VBN cord-014597-66vd2mdu 1796 39 into into IN cord-014597-66vd2mdu 1796 40 the the DT cord-014597-66vd2mdu 1796 41 medium medium NN cord-014597-66vd2mdu 1796 42 and and CC cord-014597-66vd2mdu 1796 43 remained remain VBD cord-014597-66vd2mdu 1796 44 in in IN cord-014597-66vd2mdu 1796 45 the the DT cord-014597-66vd2mdu 1796 46 cells cell NNS cord-014597-66vd2mdu 1796 47 for for IN cord-014597-66vd2mdu 1796 48 several several JJ cord-014597-66vd2mdu 1796 49 hours hour NNS cord-014597-66vd2mdu 1796 50 . . . cord-014597-66vd2mdu 1797 1 This this DT cord-014597-66vd2mdu 1797 2 result result NN cord-014597-66vd2mdu 1797 3 was be VBD cord-014597-66vd2mdu 1797 4 almost almost RB cord-014597-66vd2mdu 1797 5 the the DT cord-014597-66vd2mdu 1797 6 same same JJ cord-014597-66vd2mdu 1797 7 as as IN cord-014597-66vd2mdu 1797 8 that that DT cord-014597-66vd2mdu 1797 9 of of IN cord-014597-66vd2mdu 1797 10 studies study NNS cord-014597-66vd2mdu 1797 11 using use VBG cord-014597-66vd2mdu 1797 12 IgG1-expressing igg1-expressing NN cord-014597-66vd2mdu 1797 13 cells cell NNS cord-014597-66vd2mdu 1797 14 [ [ -LRB- cord-014597-66vd2mdu 1797 15 5 5 CD cord-014597-66vd2mdu 1797 16 , , , cord-014597-66vd2mdu 1797 17 6 6 CD cord-014597-66vd2mdu 1797 18 ] ] -RRB- cord-014597-66vd2mdu 1797 19 . . . cord-014597-66vd2mdu 1798 1 The the DT cord-014597-66vd2mdu 1798 2 localization localization NN cord-014597-66vd2mdu 1798 3 of of IN cord-014597-66vd2mdu 1798 4 IgG igg NN cord-014597-66vd2mdu 1798 5 in in IN cord-014597-66vd2mdu 1798 6 the the DT cord-014597-66vd2mdu 1798 7 cells cell NNS cord-014597-66vd2mdu 1798 8 was be VBD cord-014597-66vd2mdu 1798 9 checked check VBN cord-014597-66vd2mdu 1798 10 before before IN cord-014597-66vd2mdu 1798 11 and and CC cord-014597-66vd2mdu 1798 12 after after IN cord-014597-66vd2mdu 1798 13 the the DT cord-014597-66vd2mdu 1798 14 addition addition NN cord-014597-66vd2mdu 1798 15 of of IN cord-014597-66vd2mdu 1798 16 CHX CHX NNP cord-014597-66vd2mdu 1798 17 , , , cord-014597-66vd2mdu 1798 18 with with IN cord-014597-66vd2mdu 1798 19 the the DT cord-014597-66vd2mdu 1798 20 results result NNS cord-014597-66vd2mdu 1798 21 showing show VBG cord-014597-66vd2mdu 1798 22 that that IN cord-014597-66vd2mdu 1798 23 IgG1 IgG1 NNP cord-014597-66vd2mdu 1798 24 remained remain VBD cord-014597-66vd2mdu 1798 25 in in IN cord-014597-66vd2mdu 1798 26 the the DT cord-014597-66vd2mdu 1798 27 ER er NN cord-014597-66vd2mdu 1798 28 and and CC cord-014597-66vd2mdu 1798 29 was be VBD cord-014597-66vd2mdu 1798 30 hardly hardly RB cord-014597-66vd2mdu 1798 31 seen see VBN cord-014597-66vd2mdu 1798 32 in in IN cord-014597-66vd2mdu 1798 33 the the DT cord-014597-66vd2mdu 1798 34 Golgi Golgi NNP cord-014597-66vd2mdu 1798 35 apparatus apparatus NN cord-014597-66vd2mdu 1798 36 [ [ -LRB- cord-014597-66vd2mdu 1798 37 5 5 CD cord-014597-66vd2mdu 1798 38 ] ] -RRB- cord-014597-66vd2mdu 1798 39 [ [ -LRB- cord-014597-66vd2mdu 1798 40 6 6 CD cord-014597-66vd2mdu 1798 41 ] ] -RRB- cord-014597-66vd2mdu 1798 42 [ [ -LRB- cord-014597-66vd2mdu 1798 43 7 7 CD cord-014597-66vd2mdu 1798 44 ] ] -RRB- cord-014597-66vd2mdu 1798 45 ; ; : cord-014597-66vd2mdu 1798 46 IgG IgG NNP cord-014597-66vd2mdu 1798 47 did do VBD cord-014597-66vd2mdu 1798 48 not not RB cord-014597-66vd2mdu 1798 49 seem seem VB cord-014597-66vd2mdu 1798 50 to to TO cord-014597-66vd2mdu 1798 51 be be VB cord-014597-66vd2mdu 1798 52 efficiently efficiently RB cord-014597-66vd2mdu 1798 53 transported transport VBN cord-014597-66vd2mdu 1798 54 to to IN cord-014597-66vd2mdu 1798 55 the the DT cord-014597-66vd2mdu 1798 56 Golgi Golgi NNP cord-014597-66vd2mdu 1798 57 apparatus apparatus NN cord-014597-66vd2mdu 1798 58 . . . cord-014597-66vd2mdu 1799 1 The the DT cord-014597-66vd2mdu 1799 2 SEC SEC NNP cord-014597-66vd2mdu 1799 3 experiment experiment NN cord-014597-66vd2mdu 1799 4 showed show VBD cord-014597-66vd2mdu 1799 5 that that IN cord-014597-66vd2mdu 1799 6 most most JJS cord-014597-66vd2mdu 1799 7 of of IN cord-014597-66vd2mdu 1799 8 the the DT cord-014597-66vd2mdu 1799 9 IgG1 IgG1 NNP cord-014597-66vd2mdu 1799 10 remaining remain VBG cord-014597-66vd2mdu 1799 11 in in IN cord-014597-66vd2mdu 1799 12 the the DT cord-014597-66vd2mdu 1799 13 cell cell NN cord-014597-66vd2mdu 1799 14 seemed seem VBD cord-014597-66vd2mdu 1799 15 to to TO cord-014597-66vd2mdu 1799 16 form form VB cord-014597-66vd2mdu 1799 17 full full JJ cord-014597-66vd2mdu 1799 18 - - HYPH cord-014597-66vd2mdu 1799 19 sized sized JJ cord-014597-66vd2mdu 1799 20 antibodies antibody NNS cord-014597-66vd2mdu 1799 21 [ [ -LRB- cord-014597-66vd2mdu 1799 22 5 5 CD cord-014597-66vd2mdu 1799 23 , , , cord-014597-66vd2mdu 1799 24 6 6 CD cord-014597-66vd2mdu 1799 25 ] ] -RRB- cord-014597-66vd2mdu 1799 26 , , , cord-014597-66vd2mdu 1799 27 but but CC cord-014597-66vd2mdu 1799 28 it -PRON- PRP cord-014597-66vd2mdu 1799 29 could could MD cord-014597-66vd2mdu 1799 30 not not RB cord-014597-66vd2mdu 1799 31 be be VB cord-014597-66vd2mdu 1799 32 secreted secrete VBN cord-014597-66vd2mdu 1799 33 despite despite IN cord-014597-66vd2mdu 1799 34 this this DT cord-014597-66vd2mdu 1799 35 . . . cord-014597-66vd2mdu 1800 1 The the DT cord-014597-66vd2mdu 1800 2 high high JJ cord-014597-66vd2mdu 1800 3 - - HYPH cord-014597-66vd2mdu 1800 4 producer producer NN cord-014597-66vd2mdu 1800 5 cells cell NNS cord-014597-66vd2mdu 1800 6 could could MD cord-014597-66vd2mdu 1800 7 not not RB cord-014597-66vd2mdu 1800 8 secrete secrete VB cord-014597-66vd2mdu 1800 9 all all DT cord-014597-66vd2mdu 1800 10 of of IN cord-014597-66vd2mdu 1800 11 the the DT cord-014597-66vd2mdu 1800 12 synthesized synthesize VBN cord-014597-66vd2mdu 1800 13 IgG igg NN cord-014597-66vd2mdu 1800 14 , , , cord-014597-66vd2mdu 1800 15 and and CC cord-014597-66vd2mdu 1800 16 around around RB cord-014597-66vd2mdu 1800 17 40 40 CD cord-014597-66vd2mdu 1800 18 % % NN cord-014597-66vd2mdu 1800 19 of of IN cord-014597-66vd2mdu 1800 20 IgG igg NN cord-014597-66vd2mdu 1800 21 remained remain VBD cord-014597-66vd2mdu 1800 22 in in IN cord-014597-66vd2mdu 1800 23 the the DT cord-014597-66vd2mdu 1800 24 cells cell NNS cord-014597-66vd2mdu 1800 25 for for IN cord-014597-66vd2mdu 1800 26 several several JJ cord-014597-66vd2mdu 1800 27 hours hour NNS cord-014597-66vd2mdu 1800 28 . . . cord-014597-66vd2mdu 1801 1 This this DT cord-014597-66vd2mdu 1801 2 incomplete incomplete JJ cord-014597-66vd2mdu 1801 3 secretion secretion NN cord-014597-66vd2mdu 1801 4 is be VBZ cord-014597-66vd2mdu 1801 5 a a DT cord-014597-66vd2mdu 1801 6 common common JJ cord-014597-66vd2mdu 1801 7 phenomenon phenomenon NN cord-014597-66vd2mdu 1801 8 among among IN cord-014597-66vd2mdu 1801 9 CHO CHO NNP cord-014597-66vd2mdu 1801 10 cells cell NNS cord-014597-66vd2mdu 1801 11 producing produce VBG cord-014597-66vd2mdu 1801 12 different different JJ cord-014597-66vd2mdu 1801 13 types type NNS cord-014597-66vd2mdu 1801 14 of of IN cord-014597-66vd2mdu 1801 15 recombinant recombinant JJ cord-014597-66vd2mdu 1801 16 IgG. IgG. NNP cord-014597-66vd2mdu 1802 1 The the DT cord-014597-66vd2mdu 1802 2 IgG igg NN cord-014597-66vd2mdu 1802 3 could could MD cord-014597-66vd2mdu 1802 4 not not RB cord-014597-66vd2mdu 1802 5 be be VB cord-014597-66vd2mdu 1802 6 transported transport VBN cord-014597-66vd2mdu 1802 7 from from IN cord-014597-66vd2mdu 1802 8 the the DT cord-014597-66vd2mdu 1802 9 ER ER NNP cord-014597-66vd2mdu 1802 10 to to IN cord-014597-66vd2mdu 1802 11 the the DT cord-014597-66vd2mdu 1802 12 Golgi Golgi NNP cord-014597-66vd2mdu 1802 13 despite despite IN cord-014597-66vd2mdu 1802 14 its -PRON- PRP$ cord-014597-66vd2mdu 1802 15 formation formation NN cord-014597-66vd2mdu 1802 16 of of IN cord-014597-66vd2mdu 1802 17 fullsized fullsized JJ cord-014597-66vd2mdu 1802 18 antibodies antibody NNS cord-014597-66vd2mdu 1802 19 . . . cord-014597-66vd2mdu 1803 1 Solving solve VBG cord-014597-66vd2mdu 1803 2 this this DT cord-014597-66vd2mdu 1803 3 bottleneck bottleneck NN cord-014597-66vd2mdu 1803 4 in in IN cord-014597-66vd2mdu 1803 5 the the DT cord-014597-66vd2mdu 1803 6 transportation transportation NN cord-014597-66vd2mdu 1803 7 of of IN cord-014597-66vd2mdu 1803 8 IgG igg NN cord-014597-66vd2mdu 1803 9 from from IN cord-014597-66vd2mdu 1803 10 the the DT cord-014597-66vd2mdu 1803 11 ER ER NNP cord-014597-66vd2mdu 1803 12 to to IN cord-014597-66vd2mdu 1803 13 the the DT cord-014597-66vd2mdu 1803 14 Golgi Golgi NNP cord-014597-66vd2mdu 1803 15 and/or and/or CC cord-014597-66vd2mdu 1803 16 achieving achieve VBG cord-014597-66vd2mdu 1803 17 more more RBR cord-014597-66vd2mdu 1803 18 efficient efficient JJ cord-014597-66vd2mdu 1803 19 glycosylation glycosylation NN cord-014597-66vd2mdu 1803 20 of of IN cord-014597-66vd2mdu 1803 21 IgG igg NN cord-014597-66vd2mdu 1803 22 after after IN cord-014597-66vd2mdu 1803 23 the the DT cord-014597-66vd2mdu 1803 24 formation formation NN cord-014597-66vd2mdu 1803 25 of of IN cord-014597-66vd2mdu 1803 26 full full JJ cord-014597-66vd2mdu 1803 27 - - HYPH cord-014597-66vd2mdu 1803 28 sized sized JJ cord-014597-66vd2mdu 1803 29 antibodies antibody NNS cord-014597-66vd2mdu 1803 30 might may MD cord-014597-66vd2mdu 1803 31 be be VB cord-014597-66vd2mdu 1803 32 the the DT cord-014597-66vd2mdu 1803 33 next next JJ cord-014597-66vd2mdu 1803 34 target target NN cord-014597-66vd2mdu 1803 35 to to TO cord-014597-66vd2mdu 1803 36 improve improve VB cord-014597-66vd2mdu 1803 37 productivity productivity NN cord-014597-66vd2mdu 1803 38 . . . cord-014597-66vd2mdu 1804 1 Background background NN cord-014597-66vd2mdu 1804 2 Humanized Humanized NNP cord-014597-66vd2mdu 1804 3 monoclonal monoclonal JJ cord-014597-66vd2mdu 1804 4 antibodies antibody NNS cord-014597-66vd2mdu 1804 5 ( ( -LRB- cord-014597-66vd2mdu 1804 6 mAbs mAbs NNP cord-014597-66vd2mdu 1804 7 ) ) -RRB- cord-014597-66vd2mdu 1804 8 are be VBP cord-014597-66vd2mdu 1804 9 among among IN cord-014597-66vd2mdu 1804 10 the the DT cord-014597-66vd2mdu 1804 11 most most RBS cord-014597-66vd2mdu 1804 12 promising promising JJ cord-014597-66vd2mdu 1804 13 drugs drug NNS cord-014597-66vd2mdu 1804 14 , , , cord-014597-66vd2mdu 1804 15 but but CC cord-014597-66vd2mdu 1804 16 defined define VBN cord-014597-66vd2mdu 1804 17 strategies strategy NNS cord-014597-66vd2mdu 1804 18 for for IN cord-014597-66vd2mdu 1804 19 their -PRON- PRP$ cord-014597-66vd2mdu 1804 20 modification modification NN cord-014597-66vd2mdu 1804 21 are be VBP cord-014597-66vd2mdu 1804 22 still still RB cord-014597-66vd2mdu 1804 23 not not RB cord-014597-66vd2mdu 1804 24 available available JJ cord-014597-66vd2mdu 1804 25 . . . cord-014597-66vd2mdu 1805 1 Our -PRON- PRP$ cord-014597-66vd2mdu 1805 2 work work NN cord-014597-66vd2mdu 1805 3 deals deal NNS cord-014597-66vd2mdu 1805 4 with with IN cord-014597-66vd2mdu 1805 5 humanization humanization NN cord-014597-66vd2mdu 1805 6 of of IN cord-014597-66vd2mdu 1805 7 murine murine JJ cord-014597-66vd2mdu 1805 8 mAb2/ mAb2/ NNS cord-014597-66vd2mdu 1805 9 3H6 3h6 CD cord-014597-66vd2mdu 1805 10 . . . cord-014597-66vd2mdu 1806 1 The the DT cord-014597-66vd2mdu 1806 2 superhumanization superhumanization NN cord-014597-66vd2mdu 1806 3 approach approach NN cord-014597-66vd2mdu 1806 4 leads lead VBZ cord-014597-66vd2mdu 1806 5 to to IN cord-014597-66vd2mdu 1806 6 a a DT cord-014597-66vd2mdu 1806 7 loss loss NN cord-014597-66vd2mdu 1806 8 of of IN cord-014597-66vd2mdu 1806 9 binding bind VBG cord-014597-66vd2mdu 1806 10 affinity affinity NN cord-014597-66vd2mdu 1806 11 which which WDT cord-014597-66vd2mdu 1806 12 was be VBD cord-014597-66vd2mdu 1806 13 partially partially RB cord-014597-66vd2mdu 1806 14 restored restore VBN cord-014597-66vd2mdu 1806 15 by by IN cord-014597-66vd2mdu 1806 16 a a DT cord-014597-66vd2mdu 1806 17 single single JJ cord-014597-66vd2mdu 1806 18 human human NN cord-014597-66vd2mdu 1806 19 - - HYPH cord-014597-66vd2mdu 1806 20 to to IN cord-014597-66vd2mdu 1806 21 - - HYPH cord-014597-66vd2mdu 1806 22 mouse mouse NN cord-014597-66vd2mdu 1806 23 backmutation backmutation NN cord-014597-66vd2mdu 1806 24 ( ( -LRB- cord-014597-66vd2mdu 1806 25 T98hR t98hr NN cord-014597-66vd2mdu 1806 26 ) ) -RRB- cord-014597-66vd2mdu 1806 27 . . . cord-014597-66vd2mdu 1807 1 [ [ -LRB- cord-014597-66vd2mdu 1807 2 1 1 CD cord-014597-66vd2mdu 1807 3 ] ] -RRB- cord-014597-66vd2mdu 1808 1 This this DT cord-014597-66vd2mdu 1808 2 residue residue NN cord-014597-66vd2mdu 1808 3 was be VBD cord-014597-66vd2mdu 1808 4 selected select VBN cord-014597-66vd2mdu 1808 5 by by IN cord-014597-66vd2mdu 1808 6 synergistic synergistic JJ cord-014597-66vd2mdu 1808 7 combination combination NN cord-014597-66vd2mdu 1808 8 of of IN cord-014597-66vd2mdu 1808 9 sequence sequence NN cord-014597-66vd2mdu 1808 10 analyses analysis NNS cord-014597-66vd2mdu 1808 11 of of IN cord-014597-66vd2mdu 1808 12 antibody antibody NN cord-014597-66vd2mdu 1808 13 framework framework NN cord-014597-66vd2mdu 1808 14 regions region NNS cord-014597-66vd2mdu 1808 15 and and CC cord-014597-66vd2mdu 1808 16 structural structural JJ cord-014597-66vd2mdu 1808 17 information information NN cord-014597-66vd2mdu 1808 18 using use VBG cord-014597-66vd2mdu 1808 19 novel novel NN cord-014597-66vd2mdu 1808 20 in in IN cord-014597-66vd2mdu 1808 21 silico silico NN cord-014597-66vd2mdu 1808 22 simulations simulation NNS cord-014597-66vd2mdu 1808 23 . . . cord-014597-66vd2mdu 1809 1 For for IN cord-014597-66vd2mdu 1809 2 structural structural JJ cord-014597-66vd2mdu 1809 3 stabilization stabilization NN cord-014597-66vd2mdu 1809 4 , , , cord-014597-66vd2mdu 1809 5 a a DT cord-014597-66vd2mdu 1809 6 conglomeration conglomeration NN cord-014597-66vd2mdu 1809 7 of of IN cord-014597-66vd2mdu 1809 8 tyrosine tyrosine NN cord-014597-66vd2mdu 1809 9 residues residue NNS cord-014597-66vd2mdu 1809 10 surrounding surround VBG cord-014597-66vd2mdu 1809 11 T98hR t98hr PRP cord-014597-66vd2mdu 1809 12 was be VBD cord-014597-66vd2mdu 1809 13 identified identify VBN cord-014597-66vd2mdu 1809 14 , , , cord-014597-66vd2mdu 1809 15 the the DT cord-014597-66vd2mdu 1809 16 so so RB cord-014597-66vd2mdu 1809 17 called call VBN cord-014597-66vd2mdu 1809 18 " " `` cord-014597-66vd2mdu 1809 19 tyrosine tyrosine NN cord-014597-66vd2mdu 1809 20 cage cage NN cord-014597-66vd2mdu 1809 21 " " '' cord-014597-66vd2mdu 1809 22 . . . cord-014597-66vd2mdu 1810 1 [ [ -LRB- cord-014597-66vd2mdu 1810 2 2 2 LS cord-014597-66vd2mdu 1810 3 ] ] -RRB- cord-014597-66vd2mdu 1810 4 Analysis Analysis NNP cord-014597-66vd2mdu 1810 5 of of IN cord-014597-66vd2mdu 1810 6 the the DT cord-014597-66vd2mdu 1810 7 " " `` cord-014597-66vd2mdu 1810 8 tyrosine tyrosine NN cord-014597-66vd2mdu 1810 9 cage cage NN cord-014597-66vd2mdu 1810 10 " " '' cord-014597-66vd2mdu 1810 11 was be VBD cord-014597-66vd2mdu 1810 12 done do VBN cord-014597-66vd2mdu 1810 13 by by IN cord-014597-66vd2mdu 1810 14 alanine alanine NN cord-014597-66vd2mdu 1810 15 scanning scanning NN cord-014597-66vd2mdu 1810 16 mutations mutation NNS cord-014597-66vd2mdu 1810 17 with with IN cord-014597-66vd2mdu 1810 18 a a DT cord-014597-66vd2mdu 1810 19 double double JJ cord-014597-66vd2mdu 1810 20 mutation mutation NN cord-014597-66vd2mdu 1810 21 variant variant NN cord-014597-66vd2mdu 1810 22 T98hR t98hr NN cord-014597-66vd2mdu 1810 23 + + CC cord-014597-66vd2mdu 1810 24 Y27hA y27ha NN cord-014597-66vd2mdu 1810 25 ( ( -LRB- cord-014597-66vd2mdu 1810 26 BM09 BM09 NNP cord-014597-66vd2mdu 1810 27 ) ) -RRB- cord-014597-66vd2mdu 1810 28 and and CC cord-014597-66vd2mdu 1810 29 a a DT cord-014597-66vd2mdu 1810 30 triple triple JJ cord-014597-66vd2mdu 1810 31 mutation mutation NN cord-014597-66vd2mdu 1810 32 variant variant NN cord-014597-66vd2mdu 1810 33 T98hR t98hr XX cord-014597-66vd2mdu 1811 1 + + CC cord-014597-66vd2mdu 1812 1 Y27hA y27ha NN cord-014597-66vd2mdu 1813 1 + + CC cord-014597-66vd2mdu 1814 1 Y32hA y32ha NN cord-014597-66vd2mdu 1814 2 ( ( -LRB- cord-014597-66vd2mdu 1814 3 BM10 BM10 NNP cord-014597-66vd2mdu 1814 4 ) ) -RRB- cord-014597-66vd2mdu 1814 5 . . . cord-014597-66vd2mdu 1815 1 In in IN cord-014597-66vd2mdu 1815 2 a a DT cord-014597-66vd2mdu 1815 3 recent recent JJ cord-014597-66vd2mdu 1815 4 series series NN cord-014597-66vd2mdu 1815 5 of of IN cord-014597-66vd2mdu 1815 6 experiments experiment NNS cord-014597-66vd2mdu 1815 7 we -PRON- PRP cord-014597-66vd2mdu 1815 8 tried try VBD cord-014597-66vd2mdu 1815 9 to to TO cord-014597-66vd2mdu 1815 10 enhance enhance VB cord-014597-66vd2mdu 1815 11 binding bind VBG cord-014597-66vd2mdu 1815 12 affinity affinity NN cord-014597-66vd2mdu 1815 13 by by IN cord-014597-66vd2mdu 1815 14 three three CD cord-014597-66vd2mdu 1815 15 new new JJ cord-014597-66vd2mdu 1815 16 variants variant NNS cord-014597-66vd2mdu 1815 17 with with IN cord-014597-66vd2mdu 1815 18 backmutations backmutation NNS cord-014597-66vd2mdu 1815 19 in in IN cord-014597-66vd2mdu 1815 20 the the DT cord-014597-66vd2mdu 1815 21 variable variable JJ cord-014597-66vd2mdu 1815 22 light light JJ cord-014597-66vd2mdu 1815 23 chain chain NN cord-014597-66vd2mdu 1815 24 ( ( -LRB- cord-014597-66vd2mdu 1815 25 VL VL NNP cord-014597-66vd2mdu 1815 26 ) ) -RRB- cord-014597-66vd2mdu 1815 27 . . . cord-014597-66vd2mdu 1816 1 Originating originate VBG cord-014597-66vd2mdu 1816 2 from from IN cord-014597-66vd2mdu 1816 3 T98hR t98hr NN cord-014597-66vd2mdu 1816 4 , , , cord-014597-66vd2mdu 1816 5 residues residue NNS cord-014597-66vd2mdu 1816 6 in in IN cord-014597-66vd2mdu 1816 7 the the DT cord-014597-66vd2mdu 1816 8 VL VL NNP cord-014597-66vd2mdu 1816 9 were be VBD cord-014597-66vd2mdu 1816 10 selected select VBN cord-014597-66vd2mdu 1816 11 based base VBN cord-014597-66vd2mdu 1816 12 on on IN cord-014597-66vd2mdu 1816 13 their -PRON- PRP$ cord-014597-66vd2mdu 1816 14 spatial spatial JJ cord-014597-66vd2mdu 1816 15 proximity proximity NN cord-014597-66vd2mdu 1816 16 to to IN cord-014597-66vd2mdu 1816 17 the the DT cord-014597-66vd2mdu 1816 18 CDR3 CDR3 NNP cord-014597-66vd2mdu 1816 19 loop loop NN cord-014597-66vd2mdu 1816 20 of of IN cord-014597-66vd2mdu 1816 21 the the DT cord-014597-66vd2mdu 1816 22 variable variable JJ cord-014597-66vd2mdu 1816 23 heavy heavy JJ cord-014597-66vd2mdu 1816 24 chain chain NN cord-014597-66vd2mdu 1816 25 . . . cord-014597-66vd2mdu 1817 1 Affinity affinity NN cord-014597-66vd2mdu 1817 2 improvement improvement NN cord-014597-66vd2mdu 1817 3 of of IN cord-014597-66vd2mdu 1817 4 T98hR t98hr NN cord-014597-66vd2mdu 1817 5 was be VBD cord-014597-66vd2mdu 1817 6 evaluated evaluate VBN cord-014597-66vd2mdu 1817 7 by by IN cord-014597-66vd2mdu 1817 8 VL VL NNP cord-014597-66vd2mdu 1817 9 - - HYPH cord-014597-66vd2mdu 1817 10 double double JJ cord-014597-66vd2mdu 1817 11 backmutation backmutation NN cord-014597-66vd2mdu 1817 12 variants variant NNS cord-014597-66vd2mdu 1818 1 T98hR t98hr NN cord-014597-66vd2mdu 1819 1 + + CC cord-014597-66vd2mdu 1820 1 F46lL F46lL NNP cord-014597-66vd2mdu 1820 2 ( ( -LRB- cord-014597-66vd2mdu 1820 3 SU01 SU01 NNP cord-014597-66vd2mdu 1820 4 ) ) -RRB- cord-014597-66vd2mdu 1821 1 and and CC cord-014597-66vd2mdu 1821 2 T98hR t98hr NN cord-014597-66vd2mdu 1821 3 + + SYM cord-014597-66vd2mdu 1821 4 Q49lS Q49lS NNP cord-014597-66vd2mdu 1821 5 ( ( -LRB- cord-014597-66vd2mdu 1821 6 SU02 SU02 NNP cord-014597-66vd2mdu 1821 7 ) ) -RRB- cord-014597-66vd2mdu 1821 8 and and CC cord-014597-66vd2mdu 1821 9 a a DT cord-014597-66vd2mdu 1821 10 triple triple JJ cord-014597-66vd2mdu 1821 11 backmutation backmutation NN cord-014597-66vd2mdu 1821 12 variant variant NN cord-014597-66vd2mdu 1821 13 T98hR t98hr CD cord-014597-66vd2mdu 1821 14 + + CC cord-014597-66vd2mdu 1822 1 F46lL F46lL NNP cord-014597-66vd2mdu 1823 1 + + CC cord-014597-66vd2mdu 1823 2 Q49lS Q49lS NNP cord-014597-66vd2mdu 1823 3 ( ( -LRB- cord-014597-66vd2mdu 1823 4 SU03 SU03 NNP cord-014597-66vd2mdu 1823 5 ) ) -RRB- cord-014597-66vd2mdu 1823 6 . . . cord-014597-66vd2mdu 1824 1 All all DT cord-014597-66vd2mdu 1824 2 five five CD cord-014597-66vd2mdu 1824 3 variants variant NNS cord-014597-66vd2mdu 1824 4 were be VBD cord-014597-66vd2mdu 1824 5 expressed express VBN cord-014597-66vd2mdu 1824 6 transiently transiently RB cord-014597-66vd2mdu 1824 7 in in IN cord-014597-66vd2mdu 1824 8 HEK293 HEK293 NNP cord-014597-66vd2mdu 1824 9 - - HYPH cord-014597-66vd2mdu 1824 10 6E 6E NNP cord-014597-66vd2mdu 1824 11 cells cell NNS cord-014597-66vd2mdu 1824 12 and and CC cord-014597-66vd2mdu 1824 13 binding bind VBG cord-014597-66vd2mdu 1824 14 affinities affinity NNS cord-014597-66vd2mdu 1824 15 were be VBD cord-014597-66vd2mdu 1824 16 investigated investigate VBN cord-014597-66vd2mdu 1824 17 in in IN cord-014597-66vd2mdu 1824 18 two two CD cord-014597-66vd2mdu 1824 19 individual individual JJ cord-014597-66vd2mdu 1824 20 settings setting NNS cord-014597-66vd2mdu 1824 21 with with IN cord-014597-66vd2mdu 1824 22 bio bio NN cord-014597-66vd2mdu 1824 23 - - NN cord-014597-66vd2mdu 1824 24 layer layer NN cord-014597-66vd2mdu 1824 25 interferometry interferometry NN cord-014597-66vd2mdu 1824 26 . . . cord-014597-66vd2mdu 1825 1 In in IN cord-014597-66vd2mdu 1825 2 the the DT cord-014597-66vd2mdu 1825 3 first first JJ cord-014597-66vd2mdu 1825 4 approach approach NN cord-014597-66vd2mdu 1825 5 concentrated concentrated JJ cord-014597-66vd2mdu 1825 6 cell cell NN cord-014597-66vd2mdu 1825 7 culture culture NN cord-014597-66vd2mdu 1825 8 supernatants supernatant NNS cord-014597-66vd2mdu 1825 9 were be VBD cord-014597-66vd2mdu 1825 10 directly directly RB cord-014597-66vd2mdu 1825 11 applied apply VBN cord-014597-66vd2mdu 1825 12 and and CC cord-014597-66vd2mdu 1825 13 mAbs mAbs NNP cord-014597-66vd2mdu 1825 14 were be VBD cord-014597-66vd2mdu 1825 15 captured capture VBN cord-014597-66vd2mdu 1825 16 on on IN cord-014597-66vd2mdu 1825 17 protein protein NN cord-014597-66vd2mdu 1825 18 A a DT cord-014597-66vd2mdu 1825 19 tips tip NNS cord-014597-66vd2mdu 1825 20 , , , cord-014597-66vd2mdu 1825 21 blocked block VBN cord-014597-66vd2mdu 1825 22 with with IN cord-014597-66vd2mdu 1825 23 3D6scFv 3D6scFv NNS cord-014597-66vd2mdu 1825 24 - - HYPH cord-014597-66vd2mdu 1825 25 Fc Fc NNP cord-014597-66vd2mdu 1825 26 and and CC cord-014597-66vd2mdu 1825 27 the the DT cord-014597-66vd2mdu 1825 28 association association NN cord-014597-66vd2mdu 1825 29 and and CC cord-014597-66vd2mdu 1825 30 dissociation dissociation NN cord-014597-66vd2mdu 1825 31 of of IN cord-014597-66vd2mdu 1825 32 2F5 2f5 CD cord-014597-66vd2mdu 1825 33 IgG igg NN cord-014597-66vd2mdu 1825 34 was be VBD cord-014597-66vd2mdu 1825 35 measured measure VBN cord-014597-66vd2mdu 1825 36 . . . cord-014597-66vd2mdu 1826 1 For for IN cord-014597-66vd2mdu 1826 2 the the DT cord-014597-66vd2mdu 1826 3 second second JJ cord-014597-66vd2mdu 1826 4 approach approach NN cord-014597-66vd2mdu 1826 5 , , , cord-014597-66vd2mdu 1826 6 the the DT cord-014597-66vd2mdu 1826 7 culture culture NN cord-014597-66vd2mdu 1826 8 supernatants supernatant NNS cord-014597-66vd2mdu 1826 9 were be VBD cord-014597-66vd2mdu 1826 10 purified purify VBN cord-014597-66vd2mdu 1826 11 and and CC cord-014597-66vd2mdu 1826 12 the the DT cord-014597-66vd2mdu 1826 13 affinity affinity NN cord-014597-66vd2mdu 1826 14 was be VBD cord-014597-66vd2mdu 1826 15 determined determine VBN cord-014597-66vd2mdu 1826 16 with with IN cord-014597-66vd2mdu 1826 17 streptavidin streptavidin JJ cord-014597-66vd2mdu 1826 18 biosensors biosensor NNS cord-014597-66vd2mdu 1826 19 . . . cord-014597-66vd2mdu 1827 1 First first RB cord-014597-66vd2mdu 1827 2 , , , cord-014597-66vd2mdu 1827 3 biotinylated biotinylate VBD cord-014597-66vd2mdu 1827 4 2F5 2f5 CD cord-014597-66vd2mdu 1827 5 IgG igg NN cord-014597-66vd2mdu 1827 6 was be VBD cord-014597-66vd2mdu 1827 7 bound bind VBN cord-014597-66vd2mdu 1827 8 and and CC cord-014597-66vd2mdu 1827 9 then then RB cord-014597-66vd2mdu 1827 10 the the DT cord-014597-66vd2mdu 1827 11 association association NN cord-014597-66vd2mdu 1827 12 / / SYM cord-014597-66vd2mdu 1827 13 dissociation dissociation NN cord-014597-66vd2mdu 1827 14 of of IN cord-014597-66vd2mdu 1827 15 the the DT cord-014597-66vd2mdu 1827 16 purified purify VBN cord-014597-66vd2mdu 1827 17 3H6 3h6 CD cord-014597-66vd2mdu 1827 18 variants variant NNS cord-014597-66vd2mdu 1827 19 was be VBD cord-014597-66vd2mdu 1827 20 measured measure VBN cord-014597-66vd2mdu 1827 21 . . . cord-014597-66vd2mdu 1828 1 Affinity affinity NN cord-014597-66vd2mdu 1828 2 evaluation evaluation NN cord-014597-66vd2mdu 1828 3 of of IN cord-014597-66vd2mdu 1828 4 concentrated concentrated JJ cord-014597-66vd2mdu 1828 5 culture culture NN cord-014597-66vd2mdu 1828 6 supernatants supernatant NNS cord-014597-66vd2mdu 1828 7 with with IN cord-014597-66vd2mdu 1828 8 protein protein NN cord-014597-66vd2mdu 1828 9 A a DT cord-014597-66vd2mdu 1828 10 sensor sensor NN cord-014597-66vd2mdu 1828 11 tips tip NNS cord-014597-66vd2mdu 1828 12 showed show VBD cord-014597-66vd2mdu 1828 13 a a DT cord-014597-66vd2mdu 1828 14 decrease decrease NN cord-014597-66vd2mdu 1828 15 of of IN cord-014597-66vd2mdu 1828 16 binding bind VBG cord-014597-66vd2mdu 1828 17 affinity affinity NN cord-014597-66vd2mdu 1828 18 of of IN cord-014597-66vd2mdu 1828 19 BM09 BM09 NNP cord-014597-66vd2mdu 1828 20 and and CC cord-014597-66vd2mdu 1828 21 a a DT cord-014597-66vd2mdu 1828 22 loss loss NN cord-014597-66vd2mdu 1828 23 of of IN cord-014597-66vd2mdu 1828 24 binding binding NN cord-014597-66vd2mdu 1828 25 of of IN cord-014597-66vd2mdu 1828 26 BM10 BM10 NNP cord-014597-66vd2mdu 1828 27 . . . cord-014597-66vd2mdu 1829 1 The the DT cord-014597-66vd2mdu 1829 2 protein protein NN cord-014597-66vd2mdu 1829 3 A a DT cord-014597-66vd2mdu 1829 4 measurement measurement NN cord-014597-66vd2mdu 1829 5 showed show VBD cord-014597-66vd2mdu 1829 6 an an DT cord-014597-66vd2mdu 1829 7 increased increase VBN cord-014597-66vd2mdu 1829 8 binding binding NN cord-014597-66vd2mdu 1829 9 strength strength NN cord-014597-66vd2mdu 1829 10 of of IN cord-014597-66vd2mdu 1829 11 SU01 SU01 NNP cord-014597-66vd2mdu 1829 12 , , , cord-014597-66vd2mdu 1829 13 SU02 SU02 NNP cord-014597-66vd2mdu 1829 14 and and CC cord-014597-66vd2mdu 1829 15 SU03 SU03 NNP cord-014597-66vd2mdu 1829 16 compared compare VBN cord-014597-66vd2mdu 1829 17 to to IN cord-014597-66vd2mdu 1829 18 su3H6 su3h6 CD cord-014597-66vd2mdu 1829 19 and and CC cord-014597-66vd2mdu 1829 20 BM07 BM07 NNP cord-014597-66vd2mdu 1829 21 . . . cord-014597-66vd2mdu 1830 1 SU01 SU01 NNP cord-014597-66vd2mdu 1830 2 and and CC cord-014597-66vd2mdu 1830 3 SU03 SU03 NNP cord-014597-66vd2mdu 1830 4 result result VBP cord-014597-66vd2mdu 1830 5 in in IN cord-014597-66vd2mdu 1830 6 a a DT cord-014597-66vd2mdu 1830 7 higher high JJR cord-014597-66vd2mdu 1830 8 binding bind VBG cord-014597-66vd2mdu 1830 9 affinity affinity NN cord-014597-66vd2mdu 1830 10 compared compare VBN cord-014597-66vd2mdu 1830 11 to to IN cord-014597-66vd2mdu 1830 12 SU02 SU02 NNP cord-014597-66vd2mdu 1830 13 . . . cord-014597-66vd2mdu 1831 1 These these DT cord-014597-66vd2mdu 1831 2 results result NNS cord-014597-66vd2mdu 1831 3 can can MD cord-014597-66vd2mdu 1831 4 be be VB cord-014597-66vd2mdu 1831 5 confirmed confirm VBN cord-014597-66vd2mdu 1831 6 with with IN cord-014597-66vd2mdu 1831 7 purified purify VBN cord-014597-66vd2mdu 1831 8 variants variant NNS cord-014597-66vd2mdu 1831 9 by by IN cord-014597-66vd2mdu 1831 10 the the DT cord-014597-66vd2mdu 1831 11 streptavidin streptavidin NNP cord-014597-66vd2mdu 1831 12 bio bio NNP cord-014597-66vd2mdu 1831 13 - - HYPH cord-014597-66vd2mdu 1831 14 assay assay NN cord-014597-66vd2mdu 1831 15 ( ( -LRB- cord-014597-66vd2mdu 1831 16 Fig Fig NNP cord-014597-66vd2mdu 1831 17 . . . cord-014597-66vd2mdu 1831 18 1 1 CD cord-014597-66vd2mdu 1831 19 ) ) -RRB- cord-014597-66vd2mdu 1831 20 . . . cord-014597-66vd2mdu 1832 1 Alanine alanine NN cord-014597-66vd2mdu 1832 2 scanning scanning NN cord-014597-66vd2mdu 1832 3 of of IN cord-014597-66vd2mdu 1832 4 the the DT cord-014597-66vd2mdu 1832 5 tyrosine tyrosine NN cord-014597-66vd2mdu 1832 6 cage cage NN cord-014597-66vd2mdu 1832 7 demonstrated demonstrate VBD cord-014597-66vd2mdu 1832 8 a a DT cord-014597-66vd2mdu 1832 9 reduction reduction NN cord-014597-66vd2mdu 1832 10 of of IN cord-014597-66vd2mdu 1832 11 binding bind VBG cord-014597-66vd2mdu 1832 12 affinity affinity NN cord-014597-66vd2mdu 1832 13 ( ( -LRB- cord-014597-66vd2mdu 1832 14 BM09 BM09 NNP cord-014597-66vd2mdu 1832 15 ) ) -RRB- cord-014597-66vd2mdu 1832 16 and and CC cord-014597-66vd2mdu 1832 17 a a DT cord-014597-66vd2mdu 1832 18 severe severe JJ cord-014597-66vd2mdu 1832 19 loss loss NN cord-014597-66vd2mdu 1832 20 of of IN cord-014597-66vd2mdu 1832 21 binding bind VBG cord-014597-66vd2mdu 1832 22 ( ( -LRB- cord-014597-66vd2mdu 1832 23 BM10 BM10 NNP cord-014597-66vd2mdu 1832 24 ) ) -RRB- cord-014597-66vd2mdu 1832 25 , , , cord-014597-66vd2mdu 1832 26 concluding conclude VBG cord-014597-66vd2mdu 1832 27 that that IN cord-014597-66vd2mdu 1832 28 the the DT cord-014597-66vd2mdu 1832 29 tyrosine tyrosine NN cord-014597-66vd2mdu 1832 30 cage cage NN cord-014597-66vd2mdu 1832 31 plays play VBZ cord-014597-66vd2mdu 1832 32 an an DT cord-014597-66vd2mdu 1832 33 important important JJ cord-014597-66vd2mdu 1832 34 role role NN cord-014597-66vd2mdu 1832 35 for for IN cord-014597-66vd2mdu 1832 36 supporting support VBG cord-014597-66vd2mdu 1832 37 a a DT cord-014597-66vd2mdu 1832 38 correct correct JJ cord-014597-66vd2mdu 1832 39 CDR cdr NN cord-014597-66vd2mdu 1832 40 loop loop NN cord-014597-66vd2mdu 1832 41 conformation conformation NN cord-014597-66vd2mdu 1832 42 . . . cord-014597-66vd2mdu 1833 1 Further further JJ cord-014597-66vd2mdu 1833 2 affinity affinity NN cord-014597-66vd2mdu 1833 3 improvement improvement NN cord-014597-66vd2mdu 1833 4 of of IN cord-014597-66vd2mdu 1833 5 the the DT cord-014597-66vd2mdu 1833 6 single single JJ cord-014597-66vd2mdu 1833 7 mutation mutation NN cord-014597-66vd2mdu 1833 8 variant variant NN cord-014597-66vd2mdu 1833 9 T98hR t98hr PRP cord-014597-66vd2mdu 1833 10 could could MD cord-014597-66vd2mdu 1833 11 have have VB cord-014597-66vd2mdu 1833 12 been be VBN cord-014597-66vd2mdu 1833 13 reached reach VBN cord-014597-66vd2mdu 1833 14 via via IN cord-014597-66vd2mdu 1833 15 mutations mutation NNS cord-014597-66vd2mdu 1833 16 in in IN cord-014597-66vd2mdu 1833 17 the the DT cord-014597-66vd2mdu 1833 18 VL VL NNP cord-014597-66vd2mdu 1833 19 . . . cord-014597-66vd2mdu 1834 1 It -PRON- PRP cord-014597-66vd2mdu 1834 2 demonstrates demonstrate VBZ cord-014597-66vd2mdu 1834 3 the the DT cord-014597-66vd2mdu 1834 4 underestimated underestimated JJ cord-014597-66vd2mdu 1834 5 role role NN cord-014597-66vd2mdu 1834 6 of of IN cord-014597-66vd2mdu 1834 7 the the DT cord-014597-66vd2mdu 1834 8 VL VL NNP cord-014597-66vd2mdu 1834 9 for for IN cord-014597-66vd2mdu 1834 10 the the DT cord-014597-66vd2mdu 1834 11 interaction interaction NN cord-014597-66vd2mdu 1834 12 with with IN cord-014597-66vd2mdu 1834 13 its -PRON- PRP$ cord-014597-66vd2mdu 1834 14 binding bind VBG cord-014597-66vd2mdu 1834 15 partner partner NN cord-014597-66vd2mdu 1834 16 . . . cord-014597-66vd2mdu 1835 1 Although although IN cord-014597-66vd2mdu 1835 2 CHO CHO NNP cord-014597-66vd2mdu 1835 3 cells cell NNS cord-014597-66vd2mdu 1835 4 are be VBP cord-014597-66vd2mdu 1835 5 a a DT cord-014597-66vd2mdu 1835 6 major major JJ cord-014597-66vd2mdu 1835 7 expression expression NN cord-014597-66vd2mdu 1835 8 system system NN cord-014597-66vd2mdu 1835 9 for for IN cord-014597-66vd2mdu 1835 10 production production NN cord-014597-66vd2mdu 1835 11 of of IN cord-014597-66vd2mdu 1835 12 recombinant recombinant JJ cord-014597-66vd2mdu 1835 13 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 1835 14 , , , cord-014597-66vd2mdu 1835 15 the the DT cord-014597-66vd2mdu 1835 16 molecular molecular JJ cord-014597-66vd2mdu 1835 17 and and CC cord-014597-66vd2mdu 1835 18 cellular cellular JJ cord-014597-66vd2mdu 1835 19 background background NN cord-014597-66vd2mdu 1835 20 characterizing characterize VBG cord-014597-66vd2mdu 1835 21 a a DT cord-014597-66vd2mdu 1835 22 high high JJ cord-014597-66vd2mdu 1835 23 producer producer NN cord-014597-66vd2mdu 1835 24 is be VBZ cord-014597-66vd2mdu 1835 25 largely largely RB cord-014597-66vd2mdu 1835 26 unknown unknown JJ cord-014597-66vd2mdu 1835 27 . . . cord-014597-66vd2mdu 1836 1 It -PRON- PRP cord-014597-66vd2mdu 1836 2 has have VBZ cord-014597-66vd2mdu 1836 3 been be VBN cord-014597-66vd2mdu 1836 4 observed observe VBN cord-014597-66vd2mdu 1836 5 that that IN cord-014597-66vd2mdu 1836 6 in in IN cord-014597-66vd2mdu 1836 7 producer producer NN cord-014597-66vd2mdu 1836 8 cell cell NN cord-014597-66vd2mdu 1836 9 lines line NNS cord-014597-66vd2mdu 1836 10 important important JJ cord-014597-66vd2mdu 1836 11 signaling signal VBG cord-014597-66vd2mdu 1836 12 pathways pathway NNS cord-014597-66vd2mdu 1836 13 like like IN cord-014597-66vd2mdu 1836 14 the the DT cord-014597-66vd2mdu 1836 15 Akt Akt NNP cord-014597-66vd2mdu 1836 16 - - HYPH cord-014597-66vd2mdu 1836 17 signaling signaling NN cord-014597-66vd2mdu 1836 18 are be VBP cord-014597-66vd2mdu 1836 19 altered alter VBN cord-014597-66vd2mdu 1836 20 in in IN cord-014597-66vd2mdu 1836 21 characteristical characteristical JJ cord-014597-66vd2mdu 1836 22 ways way NNS cord-014597-66vd2mdu 1836 23 . . . cord-014597-66vd2mdu 1837 1 Thus thus RB cord-014597-66vd2mdu 1837 2 analyzing analyze VBG cord-014597-66vd2mdu 1837 3 according accord VBG cord-014597-66vd2mdu 1837 4 signaling signal VBG cord-014597-66vd2mdu 1837 5 events event NNS cord-014597-66vd2mdu 1837 6 should should MD cord-014597-66vd2mdu 1837 7 lead lead VB cord-014597-66vd2mdu 1837 8 to to IN cord-014597-66vd2mdu 1837 9 identification identification NN cord-014597-66vd2mdu 1837 10 of of IN cord-014597-66vd2mdu 1837 11 key key JJ cord-014597-66vd2mdu 1837 12 elements element NNS cord-014597-66vd2mdu 1837 13 characterizing characterize VBG cord-014597-66vd2mdu 1837 14 high high JJ cord-014597-66vd2mdu 1837 15 producer producer NN cord-014597-66vd2mdu 1837 16 cells cell NNS cord-014597-66vd2mdu 1837 17 . . . cord-014597-66vd2mdu 1838 1 To to TO cord-014597-66vd2mdu 1838 2 investigate investigate VB cord-014597-66vd2mdu 1838 3 this this DT cord-014597-66vd2mdu 1838 4 , , , cord-014597-66vd2mdu 1838 5 our -PRON- PRP$ cord-014597-66vd2mdu 1838 6 emphasis emphasis NN cord-014597-66vd2mdu 1838 7 lies lie VBZ cord-014597-66vd2mdu 1838 8 on on IN cord-014597-66vd2mdu 1838 9 the the DT cord-014597-66vd2mdu 1838 10 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1838 11 status status NN cord-014597-66vd2mdu 1838 12 of of IN cord-014597-66vd2mdu 1838 13 involved involved JJ cord-014597-66vd2mdu 1838 14 proteins protein NNS cord-014597-66vd2mdu 1838 15 as as IN cord-014597-66vd2mdu 1838 16 reversible reversible JJ cord-014597-66vd2mdu 1838 17 switches switch NNS cord-014597-66vd2mdu 1838 18 in in IN cord-014597-66vd2mdu 1838 19 all all DT cord-014597-66vd2mdu 1838 20 signaling signal VBG cord-014597-66vd2mdu 1838 21 pathways pathway NNS cord-014597-66vd2mdu 1838 22 . . . cord-014597-66vd2mdu 1839 1 We -PRON- PRP cord-014597-66vd2mdu 1839 2 aimed aim VBD cord-014597-66vd2mdu 1839 3 to to TO cord-014597-66vd2mdu 1839 4 establish establish VB cord-014597-66vd2mdu 1839 5 a a DT cord-014597-66vd2mdu 1839 6 workflow workflow NN cord-014597-66vd2mdu 1839 7 for for IN cord-014597-66vd2mdu 1839 8 CHO CHO NNP cord-014597-66vd2mdu 1839 9 - - HYPH cord-014597-66vd2mdu 1839 10 specific specific JJ cord-014597-66vd2mdu 1839 11 phosphoproteomics phosphoproteomic NNS cord-014597-66vd2mdu 1839 12 and and CC cord-014597-66vd2mdu 1839 13 focused focus VBD cord-014597-66vd2mdu 1839 14 on on IN cord-014597-66vd2mdu 1839 15 IGF IGF NNP cord-014597-66vd2mdu 1839 16 signaling signaling NN cord-014597-66vd2mdu 1839 17 , , , cord-014597-66vd2mdu 1839 18 as as IN cord-014597-66vd2mdu 1839 19 cell cell NN cord-014597-66vd2mdu 1839 20 culture culture NN cord-014597-66vd2mdu 1839 21 media medium NNS cord-014597-66vd2mdu 1839 22 often often RB cord-014597-66vd2mdu 1839 23 are be VBP cord-014597-66vd2mdu 1839 24 supplemented supplement VBN cord-014597-66vd2mdu 1839 25 with with IN cord-014597-66vd2mdu 1839 26 this this DT cord-014597-66vd2mdu 1839 27 growth growth NN cord-014597-66vd2mdu 1839 28 factor factor NN cord-014597-66vd2mdu 1839 29 . . . cord-014597-66vd2mdu 1840 1 Two two CD cord-014597-66vd2mdu 1840 2 producer producer NN cord-014597-66vd2mdu 1840 3 cell cell NN cord-014597-66vd2mdu 1840 4 lines line NNS cord-014597-66vd2mdu 1840 5 and and CC cord-014597-66vd2mdu 1840 6 the the DT cord-014597-66vd2mdu 1840 7 according accord VBG cord-014597-66vd2mdu 1840 8 parental parental JJ cord-014597-66vd2mdu 1840 9 cells cell NNS cord-014597-66vd2mdu 1840 10 were be VBD cord-014597-66vd2mdu 1840 11 cultivated cultivate VBN cord-014597-66vd2mdu 1840 12 in in IN cord-014597-66vd2mdu 1840 13 a a DT cord-014597-66vd2mdu 1840 14 stable stable JJ cord-014597-66vd2mdu 1840 15 isotope isotope NN cord-014597-66vd2mdu 1840 16 labeling labeling NN cord-014597-66vd2mdu 1840 17 with with IN cord-014597-66vd2mdu 1840 18 amino amino JJ cord-014597-66vd2mdu 1840 19 acids acid NNS cord-014597-66vd2mdu 1840 20 in in IN cord-014597-66vd2mdu 1840 21 cell cell NN cord-014597-66vd2mdu 1840 22 culture culture NN cord-014597-66vd2mdu 1840 23 ( ( -LRB- cord-014597-66vd2mdu 1840 24 SILAC SILAC NNP cord-014597-66vd2mdu 1840 25 ) ) -RRB- cord-014597-66vd2mdu 1840 26 experiment experiment NN cord-014597-66vd2mdu 1840 27 , , , cord-014597-66vd2mdu 1840 28 followed follow VBN cord-014597-66vd2mdu 1840 29 by by IN cord-014597-66vd2mdu 1840 30 quantitative quantitative JJ cord-014597-66vd2mdu 1840 31 MS MS NNP cord-014597-66vd2mdu 1840 32 phosphoproteomic phosphoproteomic NNP cord-014597-66vd2mdu 1840 33 analysis analysis NN cord-014597-66vd2mdu 1840 34 including include VBG cord-014597-66vd2mdu 1840 35 CHOspecific CHOspecific NNP cord-014597-66vd2mdu 1840 36 data data NN cord-014597-66vd2mdu 1840 37 evaluation evaluation NN cord-014597-66vd2mdu 1840 38 . . . cord-014597-66vd2mdu 1841 1 The the DT cord-014597-66vd2mdu 1841 2 chosen choose VBN cord-014597-66vd2mdu 1841 3 CHO CHO NNP cord-014597-66vd2mdu 1841 4 cell cell NN cord-014597-66vd2mdu 1841 5 lines line NNS cord-014597-66vd2mdu 1841 6 were be VBD cord-014597-66vd2mdu 1841 7 cultivated cultivate VBN cord-014597-66vd2mdu 1841 8 in in IN cord-014597-66vd2mdu 1841 9 triplicates triplicate NNS cord-014597-66vd2mdu 1841 10 in in IN cord-014597-66vd2mdu 1841 11 SILAC SILAC NNP cord-014597-66vd2mdu 1841 12 media medium NNS cord-014597-66vd2mdu 1841 13 containing contain VBG cord-014597-66vd2mdu 1841 14 isotopically isotopically RB cord-014597-66vd2mdu 1841 15 - - HYPH cord-014597-66vd2mdu 1841 16 labeled label VBN cord-014597-66vd2mdu 1841 17 lysine lysine NN cord-014597-66vd2mdu 1841 18 / / SYM cord-014597-66vd2mdu 1841 19 arginine arginine NN cord-014597-66vd2mdu 1841 20 ( ( -LRB- cord-014597-66vd2mdu 1841 21 hLys hLys NNP cord-014597-66vd2mdu 1841 22 / / SYM cord-014597-66vd2mdu 1841 23 hArg hArg NNP cord-014597-66vd2mdu 1841 24 ) ) -RRB- cord-014597-66vd2mdu 1841 25 and and CC cord-014597-66vd2mdu 1841 26 in in IN cord-014597-66vd2mdu 1841 27 parallel parallel NN cord-014597-66vd2mdu 1841 28 in in IN cord-014597-66vd2mdu 1841 29 identical identical JJ cord-014597-66vd2mdu 1841 30 standard standard JJ cord-014597-66vd2mdu 1841 31 media medium NNS cord-014597-66vd2mdu 1841 32 ( ( -LRB- cord-014597-66vd2mdu 1841 33 lLys lLys NNP cord-014597-66vd2mdu 1841 34 / / SYM cord-014597-66vd2mdu 1841 35 lArg lArg NNP cord-014597-66vd2mdu 1841 36 , , , cord-014597-66vd2mdu 1841 37 TCX10D tcx10d NN cord-014597-66vd2mdu 1841 38 , , , cord-014597-66vd2mdu 1841 39 Xell Xell NNP cord-014597-66vd2mdu 1841 40 ) ) -RRB- cord-014597-66vd2mdu 1841 41 . . . cord-014597-66vd2mdu 1842 1 Cell cell NN cord-014597-66vd2mdu 1842 2 density density NN cord-014597-66vd2mdu 1842 3 , , , cord-014597-66vd2mdu 1842 4 viability viability NN cord-014597-66vd2mdu 1842 5 , , , cord-014597-66vd2mdu 1842 6 metabolism metabolism NN cord-014597-66vd2mdu 1842 7 and and CC cord-014597-66vd2mdu 1842 8 cell cell NN cord-014597-66vd2mdu 1842 9 cycle cycle NN cord-014597-66vd2mdu 1842 10 distribution distribution NN cord-014597-66vd2mdu 1842 11 were be VBD cord-014597-66vd2mdu 1842 12 monitored monitor VBN cord-014597-66vd2mdu 1842 13 during during IN cord-014597-66vd2mdu 1842 14 50 50 CD cord-014597-66vd2mdu 1842 15 ml ml NN cord-014597-66vd2mdu 1842 16 batch batch NN cord-014597-66vd2mdu 1842 17 culture culture NN cord-014597-66vd2mdu 1842 18 for for IN cord-014597-66vd2mdu 1842 19 7 7 CD cord-014597-66vd2mdu 1842 20 - - SYM cord-014597-66vd2mdu 1842 21 8 8 CD cord-014597-66vd2mdu 1842 22 days day NNS cord-014597-66vd2mdu 1842 23 . . . cord-014597-66vd2mdu 1843 1 At at IN cord-014597-66vd2mdu 1843 2 day day NN cord-014597-66vd2mdu 1843 3 3.25 3.25 CD cord-014597-66vd2mdu 1843 4 IGF IGF NNP cord-014597-66vd2mdu 1843 5 was be VBD cord-014597-66vd2mdu 1843 6 added add VBN cord-014597-66vd2mdu 1843 7 into into IN cord-014597-66vd2mdu 1843 8 hLys hLys NNP cord-014597-66vd2mdu 1843 9 / / SYM cord-014597-66vd2mdu 1843 10 hArg hArg NNP cord-014597-66vd2mdu 1843 11 cultures culture NNS cord-014597-66vd2mdu 1843 12 . . . cord-014597-66vd2mdu 1844 1 5 5 CD cord-014597-66vd2mdu 1844 2 min min NNS cord-014597-66vd2mdu 1844 3 later later RB cord-014597-66vd2mdu 1844 4 a a DT cord-014597-66vd2mdu 1844 5 part part NN cord-014597-66vd2mdu 1844 6 of of IN cord-014597-66vd2mdu 1844 7 the the DT cord-014597-66vd2mdu 1844 8 cells cell NNS cord-014597-66vd2mdu 1844 9 was be VBD cord-014597-66vd2mdu 1844 10 harvested harvest VBN cord-014597-66vd2mdu 1844 11 . . . cord-014597-66vd2mdu 1845 1 For for IN cord-014597-66vd2mdu 1845 2 MS MS NNP cord-014597-66vd2mdu 1845 3 analysis analysis NN cord-014597-66vd2mdu 1845 4 IGF IGF NNP cord-014597-66vd2mdu 1845 5 - - HYPH cord-014597-66vd2mdu 1845 6 treated treat VBN cord-014597-66vd2mdu 1845 7 ( ( -LRB- cord-014597-66vd2mdu 1845 8 hLys hLys NNP cord-014597-66vd2mdu 1845 9 / / SYM cord-014597-66vd2mdu 1845 10 hArg hArg NNP cord-014597-66vd2mdu 1845 11 cultures culture NNS cord-014597-66vd2mdu 1845 12 ) ) -RRB- cord-014597-66vd2mdu 1845 13 and and CC cord-014597-66vd2mdu 1845 14 control control NN cord-014597-66vd2mdu 1845 15 cultures culture NNS cord-014597-66vd2mdu 1845 16 ( ( -LRB- cord-014597-66vd2mdu 1845 17 lLys lLys NNP cord-014597-66vd2mdu 1845 18 / / SYM cord-014597-66vd2mdu 1845 19 lArg lArg NNP cord-014597-66vd2mdu 1845 20 cultures culture NNS cord-014597-66vd2mdu 1845 21 ) ) -RRB- cord-014597-66vd2mdu 1845 22 were be VBD cord-014597-66vd2mdu 1845 23 combined combine VBN cord-014597-66vd2mdu 1845 24 . . . cord-014597-66vd2mdu 1846 1 The the DT cord-014597-66vd2mdu 1846 2 following follow VBG cord-014597-66vd2mdu 1846 3 MS MS NNP cord-014597-66vd2mdu 1846 4 sample sample NN cord-014597-66vd2mdu 1846 5 preparation preparation NN cord-014597-66vd2mdu 1846 6 workflow workflow NN cord-014597-66vd2mdu 1846 7 included include VBD cord-014597-66vd2mdu 1846 8 digestion digestion NN cord-014597-66vd2mdu 1846 9 of of IN cord-014597-66vd2mdu 1846 10 whole whole JJ cord-014597-66vd2mdu 1846 11 protein protein NN cord-014597-66vd2mdu 1846 12 lysate lysate NN cord-014597-66vd2mdu 1846 13 and and CC cord-014597-66vd2mdu 1846 14 phosphopeptide phosphopeptide NN cord-014597-66vd2mdu 1846 15 enrichment enrichment NN cord-014597-66vd2mdu 1846 16 via via IN cord-014597-66vd2mdu 1846 17 TIO TIO NNP cord-014597-66vd2mdu 1846 18 2beads 2beads CD cord-014597-66vd2mdu 1846 19 . . . cord-014597-66vd2mdu 1847 1 NanoLC NanoLC NNP cord-014597-66vd2mdu 1847 2 - - HYPH cord-014597-66vd2mdu 1847 3 ESI ESI NNP cord-014597-66vd2mdu 1848 1 -Orbitrap -orbitrap IN cord-014597-66vd2mdu 1848 2 MS MS NNP cord-014597-66vd2mdu 1848 3 ( ( -LRB- cord-014597-66vd2mdu 1848 4 Q Q NNP cord-014597-66vd2mdu 1848 5 Exactive Exactive NNP cord-014597-66vd2mdu 1848 6 Plus Plus NNP cord-014597-66vd2mdu 1848 7 , , , cord-014597-66vd2mdu 1848 8 Thermo Thermo NNP cord-014597-66vd2mdu 1848 9 Fisher Fisher NNP cord-014597-66vd2mdu 1848 10 Scientific Scientific NNP cord-014597-66vd2mdu 1848 11 ) ) -RRB- cord-014597-66vd2mdu 1848 12 of of IN cord-014597-66vd2mdu 1848 13 phosphopeptides phosphopeptides NNP cord-014597-66vd2mdu 1848 14 was be VBD cord-014597-66vd2mdu 1848 15 excecuted excecute VBN cord-014597-66vd2mdu 1848 16 with with IN cord-014597-66vd2mdu 1848 17 subsequent subsequent JJ cord-014597-66vd2mdu 1848 18 identification identification NN cord-014597-66vd2mdu 1848 19 and and CC cord-014597-66vd2mdu 1848 20 quantification quantification NN cord-014597-66vd2mdu 1848 21 in in IN cord-014597-66vd2mdu 1848 22 MaxQuant MaxQuant NNP cord-014597-66vd2mdu 1848 23 [ [ -LRB- cord-014597-66vd2mdu 1848 24 1 1 CD cord-014597-66vd2mdu 1848 25 ] ] -RRB- cord-014597-66vd2mdu 1848 26 . . . cord-014597-66vd2mdu 1849 1 In in IN cord-014597-66vd2mdu 1849 2 addition addition NN cord-014597-66vd2mdu 1849 3 to to IN cord-014597-66vd2mdu 1849 4 SILAC SILAC NNP cord-014597-66vd2mdu 1849 5 quantification quantification NN cord-014597-66vd2mdu 1849 6 of of IN cord-014597-66vd2mdu 1849 7 H H NNP cord-014597-66vd2mdu 1849 8 / / SYM cord-014597-66vd2mdu 1849 9 L L NNP cord-014597-66vd2mdu 1849 10 ratios ratio NNS cord-014597-66vd2mdu 1849 11 for for IN cord-014597-66vd2mdu 1849 12 investigation investigation NN cord-014597-66vd2mdu 1849 13 of of IN cord-014597-66vd2mdu 1849 14 IGF IGF NNP cord-014597-66vd2mdu 1849 15 effects effect NNS cord-014597-66vd2mdu 1849 16 , , , cord-014597-66vd2mdu 1849 17 aquired aquire VBN cord-014597-66vd2mdu 1849 18 data datum NNS cord-014597-66vd2mdu 1849 19 was be VBD cord-014597-66vd2mdu 1849 20 also also RB cord-014597-66vd2mdu 1849 21 used use VBN cord-014597-66vd2mdu 1849 22 to to TO cord-014597-66vd2mdu 1849 23 perform perform VB cord-014597-66vd2mdu 1849 24 label label NN cord-014597-66vd2mdu 1849 25 - - HYPH cord-014597-66vd2mdu 1849 26 free free JJ cord-014597-66vd2mdu 1849 27 quantification quantification NN cord-014597-66vd2mdu 1849 28 ( ( -LRB- cord-014597-66vd2mdu 1849 29 LFQ LFQ NNP cord-014597-66vd2mdu 1849 30 ) ) -RRB- cord-014597-66vd2mdu 1849 31 in in IN cord-014597-66vd2mdu 1849 32 MaxQuant MaxQuant NNP cord-014597-66vd2mdu 1849 33 [ [ -LRB- cord-014597-66vd2mdu 1849 34 1 1 CD cord-014597-66vd2mdu 1849 35 ] ] -RRB- cord-014597-66vd2mdu 1850 1 for for IN cord-014597-66vd2mdu 1850 2 comparison comparison NN cord-014597-66vd2mdu 1850 3 of of IN cord-014597-66vd2mdu 1850 4 cell cell NN cord-014597-66vd2mdu 1850 5 lines line NNS cord-014597-66vd2mdu 1850 6 . . . cord-014597-66vd2mdu 1851 1 Statistical statistical JJ cord-014597-66vd2mdu 1851 2 significance significance NN cord-014597-66vd2mdu 1851 3 was be VBD cord-014597-66vd2mdu 1851 4 calculated calculate VBN cord-014597-66vd2mdu 1851 5 via via IN cord-014597-66vd2mdu 1851 6 t t NN cord-014597-66vd2mdu 1851 7 - - HYPH cord-014597-66vd2mdu 1851 8 test test NN cord-014597-66vd2mdu 1851 9 ( ( -LRB- cord-014597-66vd2mdu 1851 10 p<0.05 p<0.05 NNP cord-014597-66vd2mdu 1851 11 ) ) -RRB- cord-014597-66vd2mdu 1851 12 or or CC cord-014597-66vd2mdu 1851 13 ANOVA ANOVA NNP cord-014597-66vd2mdu 1851 14 ( ( -LRB- cord-014597-66vd2mdu 1851 15 permutation permutation NN cord-014597-66vd2mdu 1851 16 - - HYPH cord-014597-66vd2mdu 1851 17 based base VBN cord-014597-66vd2mdu 1851 18 FDR<0.05 fdr<0.05 CD cord-014597-66vd2mdu 1851 19 ) ) -RRB- cord-014597-66vd2mdu 1851 20 in in IN cord-014597-66vd2mdu 1851 21 Perseus Perseus NNP cord-014597-66vd2mdu 1851 22 [ [ -LRB- cord-014597-66vd2mdu 1851 23 2 2 CD cord-014597-66vd2mdu 1851 24 ] ] -RRB- cord-014597-66vd2mdu 1851 25 . . . cord-014597-66vd2mdu 1852 1 Results result VBZ cord-014597-66vd2mdu 1852 2 IGF IGF NNP cord-014597-66vd2mdu 1852 3 effects effect NNS cord-014597-66vd2mdu 1852 4 on on IN cord-014597-66vd2mdu 1852 5 growth growth NN cord-014597-66vd2mdu 1852 6 and and CC cord-014597-66vd2mdu 1852 7 production production NN cord-014597-66vd2mdu 1853 1 The the DT cord-014597-66vd2mdu 1853 2 IGF IGF NNP cord-014597-66vd2mdu 1853 3 treatment treatment NN cord-014597-66vd2mdu 1853 4 resulted result VBD cord-014597-66vd2mdu 1853 5 in in IN cord-014597-66vd2mdu 1853 6 a a DT cord-014597-66vd2mdu 1853 7 prolonged prolonged JJ cord-014597-66vd2mdu 1853 8 viability viability NN cord-014597-66vd2mdu 1853 9 for for IN cord-014597-66vd2mdu 1853 10 all all DT cord-014597-66vd2mdu 1853 11 cell cell NN cord-014597-66vd2mdu 1853 12 lines line NNS cord-014597-66vd2mdu 1853 13 . . . cord-014597-66vd2mdu 1854 1 However however RB cord-014597-66vd2mdu 1854 2 , , , cord-014597-66vd2mdu 1854 3 an an DT cord-014597-66vd2mdu 1854 4 increased increase VBN cord-014597-66vd2mdu 1854 5 VCD vcd NN cord-014597-66vd2mdu 1854 6 was be VBD cord-014597-66vd2mdu 1854 7 only only RB cord-014597-66vd2mdu 1854 8 observed observe VBN cord-014597-66vd2mdu 1854 9 for for IN cord-014597-66vd2mdu 1854 10 producer producer NN cord-014597-66vd2mdu 1854 11 cell cell NN cord-014597-66vd2mdu 1854 12 line line NN cord-014597-66vd2mdu 1854 13 1 1 CD cord-014597-66vd2mdu 1854 14 , , , cord-014597-66vd2mdu 1854 15 yielding yield VBG cord-014597-66vd2mdu 1854 16 in in IN cord-014597-66vd2mdu 1854 17 an an DT cord-014597-66vd2mdu 1854 18 enhanced enhance VBN cord-014597-66vd2mdu 1854 19 integral integral NN cord-014597-66vd2mdu 1854 20 of of IN cord-014597-66vd2mdu 1854 21 VCD vcd NN cord-014597-66vd2mdu 1854 22 ( ( -LRB- cord-014597-66vd2mdu 1854 23 IVCD IVCD NNP cord-014597-66vd2mdu 1854 24 ) ) -RRB- cord-014597-66vd2mdu 1854 25 . . . cord-014597-66vd2mdu 1855 1 For for IN cord-014597-66vd2mdu 1855 2 the the DT cord-014597-66vd2mdu 1855 3 parental parental JJ cord-014597-66vd2mdu 1855 4 cells cell NNS cord-014597-66vd2mdu 1855 5 growth growth NN cord-014597-66vd2mdu 1855 6 was be VBD cord-014597-66vd2mdu 1855 7 inhibited inhibit VBN cord-014597-66vd2mdu 1855 8 by by IN cord-014597-66vd2mdu 1855 9 IGF IGF NNP cord-014597-66vd2mdu 1855 10 , , , cord-014597-66vd2mdu 1855 11 although although IN cord-014597-66vd2mdu 1855 12 S s NN cord-014597-66vd2mdu 1855 13 - - HYPH cord-014597-66vd2mdu 1855 14 phase phase NN cord-014597-66vd2mdu 1855 15 cells cell NNS cord-014597-66vd2mdu 1855 16 were be VBD cord-014597-66vd2mdu 1855 17 enriched enrich VBN cord-014597-66vd2mdu 1855 18 at at IN cord-014597-66vd2mdu 1855 19 least least JJS cord-014597-66vd2mdu 1855 20 temporary temporary JJ cord-014597-66vd2mdu 1855 21 ( ( -LRB- cord-014597-66vd2mdu 1855 22 Fig fig NN cord-014597-66vd2mdu 1855 23 . . . cord-014597-66vd2mdu 1855 24 1a 1a CD cord-014597-66vd2mdu 1855 25 ) ) -RRB- cord-014597-66vd2mdu 1855 26 . . . cord-014597-66vd2mdu 1856 1 Regarding regard VBG cord-014597-66vd2mdu 1856 2 antibody antibody NN cord-014597-66vd2mdu 1856 3 production production NN cord-014597-66vd2mdu 1856 4 IGF IGF NNP cord-014597-66vd2mdu 1856 5 led lead VBD cord-014597-66vd2mdu 1856 6 to to IN cord-014597-66vd2mdu 1856 7 a a DT cord-014597-66vd2mdu 1856 8 decreased decrease VBN cord-014597-66vd2mdu 1856 9 qP qP NNP cord-014597-66vd2mdu 1856 10 and and CC cord-014597-66vd2mdu 1856 11 product product NN cord-014597-66vd2mdu 1856 12 titer titer NN cord-014597-66vd2mdu 1856 13 , , , cord-014597-66vd2mdu 1856 14 concomitantly concomitantly RB cord-014597-66vd2mdu 1856 15 with with IN cord-014597-66vd2mdu 1856 16 an an DT cord-014597-66vd2mdu 1856 17 increase increase NN cord-014597-66vd2mdu 1856 18 in in IN cord-014597-66vd2mdu 1856 19 S s NN cord-014597-66vd2mdu 1856 20 - - HYPH cord-014597-66vd2mdu 1856 21 phase phase NN cord-014597-66vd2mdu 1856 22 cells cell NNS cord-014597-66vd2mdu 1856 23 ( ( -LRB- cord-014597-66vd2mdu 1856 24 Fig fig NN cord-014597-66vd2mdu 1856 25 . . . cord-014597-66vd2mdu 1856 26 _SP cord-014597-66vd2mdu 1856 27 1a 1a CD cord-014597-66vd2mdu 1856 28 ) ) -RRB- cord-014597-66vd2mdu 1856 29 . . . cord-014597-66vd2mdu 1857 1 This this DT cord-014597-66vd2mdu 1857 2 inverse inverse JJ cord-014597-66vd2mdu 1857 3 correlation correlation NN cord-014597-66vd2mdu 1857 4 of of IN cord-014597-66vd2mdu 1857 5 proliferation proliferation NN cord-014597-66vd2mdu 1857 6 and and CC cord-014597-66vd2mdu 1857 7 cell cell NN cord-014597-66vd2mdu 1857 8 specific specific JJ cord-014597-66vd2mdu 1857 9 productivity productivity NN cord-014597-66vd2mdu 1857 10 is be VBZ cord-014597-66vd2mdu 1857 11 known know VBN cord-014597-66vd2mdu 1857 12 from from IN cord-014597-66vd2mdu 1857 13 different different JJ cord-014597-66vd2mdu 1857 14 productivity productivity NN cord-014597-66vd2mdu 1857 15 enhancing enhance VBG cord-014597-66vd2mdu 1857 16 molecules molecule NNS cord-014597-66vd2mdu 1857 17 , , , cord-014597-66vd2mdu 1857 18 like like IN cord-014597-66vd2mdu 1857 19 butyrate butyrate NN cord-014597-66vd2mdu 1857 20 [ [ -LRB- cord-014597-66vd2mdu 1857 21 3 3 CD cord-014597-66vd2mdu 1857 22 ] ] -RRB- cord-014597-66vd2mdu 1857 23 . . . cord-014597-66vd2mdu 1858 1 MS MS NNP cord-014597-66vd2mdu 1858 2 investigation investigation NN cord-014597-66vd2mdu 1858 3 of of IN cord-014597-66vd2mdu 1858 4 signaling signal VBG cord-014597-66vd2mdu 1858 5 events event NNS cord-014597-66vd2mdu 1858 6 The the DT cord-014597-66vd2mdu 1858 7 phosphoproteomic phosphoproteomic JJ cord-014597-66vd2mdu 1858 8 experiment experiment NN cord-014597-66vd2mdu 1858 9 resulted result VBD cord-014597-66vd2mdu 1858 10 in in IN cord-014597-66vd2mdu 1858 11 the the DT cord-014597-66vd2mdu 1858 12 identification identification NN cord-014597-66vd2mdu 1858 13 of of IN cord-014597-66vd2mdu 1858 14 10.485 10.485 CD cord-014597-66vd2mdu 1858 15 class class NN cord-014597-66vd2mdu 1858 16 I i NN cord-014597-66vd2mdu 1858 17 - - HYPH cord-014597-66vd2mdu 1858 18 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1858 19 sites site NNS cord-014597-66vd2mdu 1858 20 . . . cord-014597-66vd2mdu 1859 1 Statistical statistical JJ cord-014597-66vd2mdu 1859 2 evaluation evaluation NN cord-014597-66vd2mdu 1859 3 of of IN cord-014597-66vd2mdu 1859 4 phosphopeptide phosphopeptide JJ cord-014597-66vd2mdu 1859 5 abundances abundance NNS cord-014597-66vd2mdu 1859 6 in in IN cord-014597-66vd2mdu 1859 7 Perseus Perseus NNP cord-014597-66vd2mdu 1859 8 showed show VBD cord-014597-66vd2mdu 1859 9 up up RP cord-014597-66vd2mdu 1859 10 144 144 CD cord-014597-66vd2mdu 1859 11 significant significant JJ cord-014597-66vd2mdu 1859 12 differences difference NNS cord-014597-66vd2mdu 1859 13 between between IN cord-014597-66vd2mdu 1859 14 the the DT cord-014597-66vd2mdu 1859 15 cell cell NN cord-014597-66vd2mdu 1859 16 lines line NNS cord-014597-66vd2mdu 1859 17 and and CC cord-014597-66vd2mdu 1859 18 led lead VBD cord-014597-66vd2mdu 1859 19 to to IN cord-014597-66vd2mdu 1859 20 producer producer NN cord-014597-66vd2mdu 1859 21 vs. vs. FW cord-014597-66vd2mdu 1859 22 parental parental JJ cord-014597-66vd2mdu 1859 23 classifications classification NNS cord-014597-66vd2mdu 1859 24 ( ( -LRB- cord-014597-66vd2mdu 1859 25 Fig Fig NNP cord-014597-66vd2mdu 1859 26 . . . cord-014597-66vd2mdu 1859 27 1b 1b CD cord-014597-66vd2mdu 1859 28 ) ) -RRB- cord-014597-66vd2mdu 1859 29 . . . cord-014597-66vd2mdu 1860 1 The the DT cord-014597-66vd2mdu 1860 2 quantitative quantitative JJ cord-014597-66vd2mdu 1860 3 evaluation evaluation NN cord-014597-66vd2mdu 1860 4 via via IN cord-014597-66vd2mdu 1860 5 SILAC SILAC NNP cord-014597-66vd2mdu 1860 6 yielded yield VBD cord-014597-66vd2mdu 1860 7 in in IN cord-014597-66vd2mdu 1860 8 about about RB cord-014597-66vd2mdu 1860 9 2.408 2.408 CD cord-014597-66vd2mdu 1860 10 quantifiable quantifiable JJ cord-014597-66vd2mdu 1860 11 phosphosites phosphosite NNS cord-014597-66vd2mdu 1860 12 in in IN cord-014597-66vd2mdu 1860 13 at at RB cord-014597-66vd2mdu 1860 14 least least RBS cord-014597-66vd2mdu 1860 15 6 6 CD cord-014597-66vd2mdu 1860 16 biological biological JJ cord-014597-66vd2mdu 1860 17 replicates replicate NNS cord-014597-66vd2mdu 1860 18 . . . cord-014597-66vd2mdu 1861 1 Rapid rapid JJ cord-014597-66vd2mdu 1861 2 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1861 3 changes change NNS cord-014597-66vd2mdu 1861 4 after after IN cord-014597-66vd2mdu 1861 5 growth growth NN cord-014597-66vd2mdu 1861 6 factor factor NN cord-014597-66vd2mdu 1861 7 treatment treatment NN cord-014597-66vd2mdu 1861 8 indicated indicate VBD cord-014597-66vd2mdu 1861 9 signaling signal VBG cord-014597-66vd2mdu 1861 10 towards towards IN cord-014597-66vd2mdu 1861 11 protein protein NN cord-014597-66vd2mdu 1861 12 synthesis synthesis NN cord-014597-66vd2mdu 1861 13 , , , cord-014597-66vd2mdu 1861 14 cell cell NN cord-014597-66vd2mdu 1861 15 cycle cycle NN cord-014597-66vd2mdu 1861 16 and and CC cord-014597-66vd2mdu 1861 17 regulation regulation NN cord-014597-66vd2mdu 1861 18 of of IN cord-014597-66vd2mdu 1861 19 actin actin NN cord-014597-66vd2mdu 1861 20 cytoskeleton cytoskeleton NN cord-014597-66vd2mdu 1861 21 amongst amongst IN cord-014597-66vd2mdu 1861 22 others other NNS cord-014597-66vd2mdu 1861 23 . . . cord-014597-66vd2mdu 1862 1 For for IN cord-014597-66vd2mdu 1862 2 201 201 CD cord-014597-66vd2mdu 1862 3 phosphosites phosphosite NNS cord-014597-66vd2mdu 1862 4 significantly significantly RB cord-014597-66vd2mdu 1862 5 different different JJ cord-014597-66vd2mdu 1862 6 H H NNP cord-014597-66vd2mdu 1862 7 / / SYM cord-014597-66vd2mdu 1862 8 L l NN cord-014597-66vd2mdu 1862 9 ratios ratio NNS cord-014597-66vd2mdu 1862 10 were be VBD cord-014597-66vd2mdu 1862 11 calculated calculate VBN cord-014597-66vd2mdu 1862 12 between between IN cord-014597-66vd2mdu 1862 13 the the DT cord-014597-66vd2mdu 1862 14 two two CD cord-014597-66vd2mdu 1862 15 groups group NNS cord-014597-66vd2mdu 1862 16 parental parental JJ cord-014597-66vd2mdu 1862 17 vs. vs. NN cord-014597-66vd2mdu 1862 18 producer producer NN cord-014597-66vd2mdu 1862 19 , , , cord-014597-66vd2mdu 1862 20 four four CD cord-014597-66vd2mdu 1862 21 of of IN cord-014597-66vd2mdu 1862 22 them -PRON- PRP cord-014597-66vd2mdu 1862 23 are be VBP cord-014597-66vd2mdu 1862 24 listed list VBN cord-014597-66vd2mdu 1863 1 ( ( -LRB- cord-014597-66vd2mdu 1863 2 Table table NN cord-014597-66vd2mdu 1863 3 1 1 CD cord-014597-66vd2mdu 1863 4 ) ) -RRB- cord-014597-66vd2mdu 1863 5 . . . cord-014597-66vd2mdu 1864 1 The the DT cord-014597-66vd2mdu 1864 2 workflow workflow NN cord-014597-66vd2mdu 1864 3 to to TO cord-014597-66vd2mdu 1864 4 study study VB cord-014597-66vd2mdu 1864 5 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1864 6 states state NNS cord-014597-66vd2mdu 1864 7 revealed reveal VBD cord-014597-66vd2mdu 1864 8 differences difference NNS cord-014597-66vd2mdu 1864 9 in in IN cord-014597-66vd2mdu 1864 10 the the DT cord-014597-66vd2mdu 1864 11 related related JJ cord-014597-66vd2mdu 1864 12 cell cell NN cord-014597-66vd2mdu 1864 13 lines line NNS cord-014597-66vd2mdu 1864 14 and and CC cord-014597-66vd2mdu 1864 15 gave give VBD cord-014597-66vd2mdu 1864 16 insights insight NNS cord-014597-66vd2mdu 1864 17 into into IN cord-014597-66vd2mdu 1864 18 signal signal NN cord-014597-66vd2mdu 1864 19 transduction transduction NN cord-014597-66vd2mdu 1864 20 as as IN cord-014597-66vd2mdu 1864 21 a a DT cord-014597-66vd2mdu 1864 22 response response NN cord-014597-66vd2mdu 1864 23 on on IN cord-014597-66vd2mdu 1864 24 IGF IGF NNP cord-014597-66vd2mdu 1864 25 . . . cord-014597-66vd2mdu 1865 1 On on IN cord-014597-66vd2mdu 1865 2 the the DT cord-014597-66vd2mdu 1865 3 one one CD cord-014597-66vd2mdu 1865 4 hand hand NN cord-014597-66vd2mdu 1865 5 , , , cord-014597-66vd2mdu 1865 6 IGF IGF NNP cord-014597-66vd2mdu 1865 7 - - HYPH cord-014597-66vd2mdu 1865 8 treatment treatment NN cord-014597-66vd2mdu 1865 9 resulted result VBD cord-014597-66vd2mdu 1865 10 in in IN cord-014597-66vd2mdu 1865 11 a a DT cord-014597-66vd2mdu 1865 12 fast fast JJ cord-014597-66vd2mdu 1865 13 and and CC cord-014597-66vd2mdu 1865 14 widespread widespread JJ cord-014597-66vd2mdu 1865 15 upregulation upregulation NN cord-014597-66vd2mdu 1865 16 of of IN cord-014597-66vd2mdu 1865 17 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1865 18 sites site NNS cord-014597-66vd2mdu 1865 19 within within IN cord-014597-66vd2mdu 1865 20 Aktand Aktand NNP cord-014597-66vd2mdu 1865 21 MAPK MAPK NNP cord-014597-66vd2mdu 1865 22 - - HYPH cord-014597-66vd2mdu 1865 23 signaling signal VBG cord-014597-66vd2mdu 1865 24 . . . cord-014597-66vd2mdu 1866 1 On on IN cord-014597-66vd2mdu 1866 2 the the DT cord-014597-66vd2mdu 1866 3 other other JJ cord-014597-66vd2mdu 1866 4 hand hand NN cord-014597-66vd2mdu 1866 5 , , , cord-014597-66vd2mdu 1866 6 a a DT cord-014597-66vd2mdu 1866 7 different different JJ cord-014597-66vd2mdu 1866 8 phosphorylation phosphorylation NN cord-014597-66vd2mdu 1866 9 status status NN cord-014597-66vd2mdu 1866 10 for for IN cord-014597-66vd2mdu 1866 11 producer producer NN cord-014597-66vd2mdu 1866 12 compared compare VBN cord-014597-66vd2mdu 1866 13 to to IN cord-014597-66vd2mdu 1866 14 parental parental JJ cord-014597-66vd2mdu 1866 15 cell cell NN cord-014597-66vd2mdu 1866 16 lines line NNS cord-014597-66vd2mdu 1866 17 uncovered uncover VBD cord-014597-66vd2mdu 1866 18 distinctions distinction NNS cord-014597-66vd2mdu 1866 19 in in IN cord-014597-66vd2mdu 1866 20 biological biological JJ cord-014597-66vd2mdu 1866 21 processes process NNS cord-014597-66vd2mdu 1866 22 like like IN cord-014597-66vd2mdu 1866 23 RNA RNA NNP cord-014597-66vd2mdu 1866 24 - - : cord-014597-66vd2mdu 1866 25 and and CC cord-014597-66vd2mdu 1866 26 DNA dna NN cord-014597-66vd2mdu 1866 27 - - HYPH cord-014597-66vd2mdu 1866 28 binding binding NN cord-014597-66vd2mdu 1866 29 and and CC cord-014597-66vd2mdu 1866 30 regulation regulation NN cord-014597-66vd2mdu 1866 31 of of IN cord-014597-66vd2mdu 1866 32 cytoskeleton cytoskeleton NN cord-014597-66vd2mdu 1866 33 . . . cord-014597-66vd2mdu 1867 1 In in IN cord-014597-66vd2mdu 1867 2 sum sum NN cord-014597-66vd2mdu 1867 3 , , , cord-014597-66vd2mdu 1867 4 our -PRON- PRP$ cord-014597-66vd2mdu 1867 5 sucessfully sucessfully RB cord-014597-66vd2mdu 1867 6 established establish VBN cord-014597-66vd2mdu 1867 7 phosphoproteomic phosphoproteomic JJ cord-014597-66vd2mdu 1867 8 approach approach NN cord-014597-66vd2mdu 1867 9 allows allow VBZ cord-014597-66vd2mdu 1867 10 to to TO cord-014597-66vd2mdu 1867 11 detect detect VB cord-014597-66vd2mdu 1867 12 important important JJ cord-014597-66vd2mdu 1867 13 signaling signal VBG cord-014597-66vd2mdu 1867 14 key key JJ cord-014597-66vd2mdu 1867 15 players player NNS cord-014597-66vd2mdu 1867 16 in in IN cord-014597-66vd2mdu 1867 17 CHO CHO NNP cord-014597-66vd2mdu 1867 18 cells cell NNS cord-014597-66vd2mdu 1867 19 that that WDT cord-014597-66vd2mdu 1867 20 subsequently subsequently RB cord-014597-66vd2mdu 1867 21 can can MD cord-014597-66vd2mdu 1867 22 be be VB cord-014597-66vd2mdu 1867 23 targeted target VBN cord-014597-66vd2mdu 1867 24 through through IN cord-014597-66vd2mdu 1867 25 cell cell NN cord-014597-66vd2mdu 1867 26 engineering engineering NN cord-014597-66vd2mdu 1867 27 or or CC cord-014597-66vd2mdu 1867 28 small small JJ cord-014597-66vd2mdu 1867 29 molecule molecule NN cord-014597-66vd2mdu 1867 30 treatment treatment NN cord-014597-66vd2mdu 1867 31 . . . cord-014597-66vd2mdu 1868 1 To to TO cord-014597-66vd2mdu 1868 2 improve improve VB cord-014597-66vd2mdu 1868 3 antibody antibody NN cord-014597-66vd2mdu 1868 4 production production NN cord-014597-66vd2mdu 1868 5 in in IN cord-014597-66vd2mdu 1868 6 the the DT cord-014597-66vd2mdu 1868 7 CHO CHO NNP cord-014597-66vd2mdu 1868 8 cell cell NN cord-014597-66vd2mdu 1868 9 expression expression NN cord-014597-66vd2mdu 1868 10 system system NN cord-014597-66vd2mdu 1868 11 , , , cord-014597-66vd2mdu 1868 12 it -PRON- PRP cord-014597-66vd2mdu 1868 13 seems seem VBZ cord-014597-66vd2mdu 1868 14 to to TO cord-014597-66vd2mdu 1868 15 be be VB cord-014597-66vd2mdu 1868 16 useful useful JJ cord-014597-66vd2mdu 1868 17 to to TO cord-014597-66vd2mdu 1868 18 up up IN cord-014597-66vd2mdu 1868 19 - - : cord-014597-66vd2mdu 1868 20 or or CC cord-014597-66vd2mdu 1868 21 downregulate downregulate VB cord-014597-66vd2mdu 1868 22 gene gene NN cord-014597-66vd2mdu 1868 23 expression expression NN cord-014597-66vd2mdu 1868 24 including include VBG cord-014597-66vd2mdu 1868 25 antibody antibody NN cord-014597-66vd2mdu 1868 26 folding folding NN cord-014597-66vd2mdu 1868 27 , , , cord-014597-66vd2mdu 1868 28 secretion secretion NN cord-014597-66vd2mdu 1868 29 , , , cord-014597-66vd2mdu 1868 30 and and CC cord-014597-66vd2mdu 1868 31 cell cell NN cord-014597-66vd2mdu 1868 32 metabolism metabolism NN cord-014597-66vd2mdu 1868 33 . . . cord-014597-66vd2mdu 1869 1 Many many JJ cord-014597-66vd2mdu 1869 2 cell cell NN cord-014597-66vd2mdu 1869 3 engineering engineering NN cord-014597-66vd2mdu 1869 4 approaches approach NNS cord-014597-66vd2mdu 1869 5 , , , cord-014597-66vd2mdu 1869 6 including include VBG cord-014597-66vd2mdu 1869 7 gene gene NN cord-014597-66vd2mdu 1869 8 introduction introduction NN cord-014597-66vd2mdu 1869 9 , , , cord-014597-66vd2mdu 1869 10 knockout knockout NN cord-014597-66vd2mdu 1869 11 and and CC cord-014597-66vd2mdu 1869 12 knockdown knockdown NN cord-014597-66vd2mdu 1869 13 , , , cord-014597-66vd2mdu 1869 14 have have VBP cord-014597-66vd2mdu 1869 15 been be VBN cord-014597-66vd2mdu 1869 16 employed employ VBN cord-014597-66vd2mdu 1869 17 to to TO cord-014597-66vd2mdu 1869 18 enhance enhance VB cord-014597-66vd2mdu 1869 19 recombinant recombinant JJ cord-014597-66vd2mdu 1869 20 antibody antibody NN cord-014597-66vd2mdu 1869 21 production production NN cord-014597-66vd2mdu 1869 22 [ [ -LRB- cord-014597-66vd2mdu 1869 23 1 1 CD cord-014597-66vd2mdu 1869 24 ] ] -RRB- cord-014597-66vd2mdu 1869 25 . . . cord-014597-66vd2mdu 1870 1 However however RB cord-014597-66vd2mdu 1870 2 , , , cord-014597-66vd2mdu 1870 3 identifying identify VBG cord-014597-66vd2mdu 1870 4 production production NN cord-014597-66vd2mdu 1870 5 enhancer enhancer NN cord-014597-66vd2mdu 1870 6 genes gene NNS cord-014597-66vd2mdu 1870 7 is be VBZ cord-014597-66vd2mdu 1870 8 the the DT cord-014597-66vd2mdu 1870 9 rate rate NN cord-014597-66vd2mdu 1870 10 - - HYPH cord-014597-66vd2mdu 1870 11 limiting limit VBG cord-014597-66vd2mdu 1870 12 step step NN cord-014597-66vd2mdu 1870 13 for for IN cord-014597-66vd2mdu 1870 14 CHO CHO NNP cord-014597-66vd2mdu 1870 15 cell cell NN cord-014597-66vd2mdu 1870 16 engineering engineering NN cord-014597-66vd2mdu 1870 17 , , , cord-014597-66vd2mdu 1870 18 because because IN cord-014597-66vd2mdu 1870 19 the the DT cord-014597-66vd2mdu 1870 20 conventional conventional JJ cord-014597-66vd2mdu 1870 21 method method NN cord-014597-66vd2mdu 1870 22 requires require VBZ cord-014597-66vd2mdu 1870 23 a a DT cord-014597-66vd2mdu 1870 24 series series NN cord-014597-66vd2mdu 1870 25 of of IN cord-014597-66vd2mdu 1870 26 experiments experiment NNS cord-014597-66vd2mdu 1870 27 including include VBG cord-014597-66vd2mdu 1870 28 genomic genomic JJ cord-014597-66vd2mdu 1870 29 integration integration NN cord-014597-66vd2mdu 1870 30 of of IN cord-014597-66vd2mdu 1870 31 the the DT cord-014597-66vd2mdu 1870 32 tested test VBN cord-014597-66vd2mdu 1870 33 genes gene NNS cord-014597-66vd2mdu 1870 34 , , , cord-014597-66vd2mdu 1870 35 selection selection NN cord-014597-66vd2mdu 1870 36 of of IN cord-014597-66vd2mdu 1870 37 stable stable JJ cord-014597-66vd2mdu 1870 38 cell cell NN cord-014597-66vd2mdu 1870 39 clones clone NNS cord-014597-66vd2mdu 1870 40 and and CC cord-014597-66vd2mdu 1870 41 cell cell NN cord-014597-66vd2mdu 1870 42 culture culture NN cord-014597-66vd2mdu 1870 43 experiments experiment NNS cord-014597-66vd2mdu 1870 44 of of IN cord-014597-66vd2mdu 1870 45 several several JJ cord-014597-66vd2mdu 1870 46 clones clone NNS cord-014597-66vd2mdu 1870 47 . . . cord-014597-66vd2mdu 1871 1 In in IN cord-014597-66vd2mdu 1871 2 this this DT cord-014597-66vd2mdu 1871 3 study study NN cord-014597-66vd2mdu 1871 4 , , , cord-014597-66vd2mdu 1871 5 we -PRON- PRP cord-014597-66vd2mdu 1871 6 propose propose VBP cord-014597-66vd2mdu 1871 7 an an DT cord-014597-66vd2mdu 1871 8 approach approach NN cord-014597-66vd2mdu 1871 9 for for IN cord-014597-66vd2mdu 1871 10 rapid rapid JJ cord-014597-66vd2mdu 1871 11 evaluation evaluation NN cord-014597-66vd2mdu 1871 12 of of IN cord-014597-66vd2mdu 1871 13 production production NN cord-014597-66vd2mdu 1871 14 enhancer enhancer NN cord-014597-66vd2mdu 1871 15 genes gene NNS cord-014597-66vd2mdu 1871 16 based base VBN cord-014597-66vd2mdu 1871 17 on on IN cord-014597-66vd2mdu 1871 18 an an DT cord-014597-66vd2mdu 1871 19 episomal episomal JJ cord-014597-66vd2mdu 1871 20 expression expression NN cord-014597-66vd2mdu 1871 21 system system NN cord-014597-66vd2mdu 1871 22 . . . cord-014597-66vd2mdu 1872 1 Plasmid plasmid NN cord-014597-66vd2mdu 1872 2 vector vector NN cord-014597-66vd2mdu 1872 3 carrying carry VBG cord-014597-66vd2mdu 1872 4 the the DT cord-014597-66vd2mdu 1872 5 Epstein Epstein NNP cord-014597-66vd2mdu 1872 6 - - HYPH cord-014597-66vd2mdu 1872 7 Barr Barr NNP cord-014597-66vd2mdu 1872 8 virus virus NN cord-014597-66vd2mdu 1872 9 ( ( -LRB- cord-014597-66vd2mdu 1872 10 EBV EBV NNP cord-014597-66vd2mdu 1872 11 ) ) -RRB- cord-014597-66vd2mdu 1872 12 encoded encode VBD cord-014597-66vd2mdu 1872 13 nuclear nuclear JJ cord-014597-66vd2mdu 1872 14 antigen antigen NN cord-014597-66vd2mdu 1872 15 1 1 CD cord-014597-66vd2mdu 1873 1 ( ( -LRB- cord-014597-66vd2mdu 1873 2 EBNA1 EBNA1 NNP cord-014597-66vd2mdu 1873 3 ) ) -RRB- cord-014597-66vd2mdu 1873 4 was be VBD cord-014597-66vd2mdu 1873 5 transfected transfecte VBN cord-014597-66vd2mdu 1873 6 into into IN cord-014597-66vd2mdu 1873 7 CHO CHO NNP cord-014597-66vd2mdu 1873 8 cell cell NN cord-014597-66vd2mdu 1873 9 line line NN cord-014597-66vd2mdu 1873 10 producing produce VBG cord-014597-66vd2mdu 1873 11 IgG1 IgG1 NNP cord-014597-66vd2mdu 1873 12 antibody antibody NN cord-014597-66vd2mdu 1873 13 . . . cord-014597-66vd2mdu 1874 1 After after IN cord-014597-66vd2mdu 1874 2 G418 G418 NNPS cord-014597-66vd2mdu 1874 3 selection selection NN cord-014597-66vd2mdu 1874 4 and and CC cord-014597-66vd2mdu 1874 5 single single JJ cord-014597-66vd2mdu 1874 6 colony colony NN cord-014597-66vd2mdu 1874 7 isolation isolation NN cord-014597-66vd2mdu 1874 8 , , , cord-014597-66vd2mdu 1874 9 EBNA1 EBNA1 NNS cord-014597-66vd2mdu 1874 10 expression expression NN cord-014597-66vd2mdu 1874 11 was be VBD cord-014597-66vd2mdu 1874 12 checked check VBN cord-014597-66vd2mdu 1874 13 with with IN cord-014597-66vd2mdu 1874 14 capillary capillary JJ cord-014597-66vd2mdu 1874 15 electrophoresis electrophoresis NN cord-014597-66vd2mdu 1874 16 system system NN cord-014597-66vd2mdu 1874 17 Wes Wes NNP cord-014597-66vd2mdu 1874 18 ( ( -LRB- cord-014597-66vd2mdu 1874 19 ProteinSimple ProteinSimple NNP cord-014597-66vd2mdu 1874 20 ) ) -RRB- cord-014597-66vd2mdu 1874 21 . . . cord-014597-66vd2mdu 1875 1 EBV EBV NNP cord-014597-66vd2mdu 1875 2 EBNA1-antibody EBNA1-antibody NNP cord-014597-66vd2mdu 1875 3 ( ( -LRB- cord-014597-66vd2mdu 1875 4 1EB12 1EB12 NNS cord-014597-66vd2mdu 1875 5 ) ) -RRB- cord-014597-66vd2mdu 1875 6 was be VBD cord-014597-66vd2mdu 1875 7 used use VBN cord-014597-66vd2mdu 1875 8 for for IN cord-014597-66vd2mdu 1875 9 detection detection NN cord-014597-66vd2mdu 1875 10 as as IN cord-014597-66vd2mdu 1875 11 the the DT cord-014597-66vd2mdu 1875 12 primary primary JJ cord-014597-66vd2mdu 1875 13 antibody antibody NN cord-014597-66vd2mdu 1875 14 . . . cord-014597-66vd2mdu 1876 1 The the DT cord-014597-66vd2mdu 1876 2 expression expression NN cord-014597-66vd2mdu 1876 3 vector vector NN cord-014597-66vd2mdu 1876 4 for for IN cord-014597-66vd2mdu 1876 5 the the DT cord-014597-66vd2mdu 1876 6 gene gene NN cord-014597-66vd2mdu 1876 7 of of IN cord-014597-66vd2mdu 1876 8 interest interest NN cord-014597-66vd2mdu 1876 9 was be VBD cord-014597-66vd2mdu 1876 10 prepared prepare VBN cord-014597-66vd2mdu 1876 11 by by IN cord-014597-66vd2mdu 1876 12 inserting insert VBG cord-014597-66vd2mdu 1876 13 1508 1508 CD cord-014597-66vd2mdu 1876 14 bp bp NNP cord-014597-66vd2mdu 1876 15 of of IN cord-014597-66vd2mdu 1876 16 an an DT cord-014597-66vd2mdu 1876 17 oriP orip CD cord-014597-66vd2mdu 1876 18 DNA dna NN cord-014597-66vd2mdu 1876 19 sequence sequence NN cord-014597-66vd2mdu 1876 20 into into IN cord-014597-66vd2mdu 1876 21 a a DT cord-014597-66vd2mdu 1876 22 plasmid plasmid NN cord-014597-66vd2mdu 1876 23 vector vector NN cord-014597-66vd2mdu 1876 24 carrying carry VBG cord-014597-66vd2mdu 1876 25 CAG CAG NNP cord-014597-66vd2mdu 1876 26 promoter promoter NN cord-014597-66vd2mdu 1876 27 , , , cord-014597-66vd2mdu 1876 28 resulting result VBG cord-014597-66vd2mdu 1876 29 in in IN cord-014597-66vd2mdu 1876 30 the the DT cord-014597-66vd2mdu 1876 31 pOTC potc NN cord-014597-66vd2mdu 1876 32 vector vector NN cord-014597-66vd2mdu 1876 33 . . . cord-014597-66vd2mdu 1877 1 PEI PEI NNP cord-014597-66vd2mdu 1877 2 max max NNP cord-014597-66vd2mdu 1877 3 ( ( -LRB- cord-014597-66vd2mdu 1877 4 Polysciences Polysciences NNP cord-014597-66vd2mdu 1877 5 , , , cord-014597-66vd2mdu 1877 6 Inc. Inc. NNP cord-014597-66vd2mdu 1877 7 ) ) -RRB- cord-014597-66vd2mdu 1877 8 and and CC cord-014597-66vd2mdu 1877 9 BalanCD BalanCD NNP cord-014597-66vd2mdu 1877 10 Transfectory Transfectory NNP cord-014597-66vd2mdu 1877 11 CHO CHO NNP cord-014597-66vd2mdu 1877 12 ( ( -LRB- cord-014597-66vd2mdu 1877 13 Irvine Irvine NNP cord-014597-66vd2mdu 1877 14 Scientific Scientific NNP cord-014597-66vd2mdu 1877 15 ) ) -RRB- cord-014597-66vd2mdu 1877 16 were be VBD cord-014597-66vd2mdu 1877 17 used use VBN cord-014597-66vd2mdu 1877 18 for for IN cord-014597-66vd2mdu 1877 19 the the DT cord-014597-66vd2mdu 1877 20 transfection transfection NN cord-014597-66vd2mdu 1877 21 . . . cord-014597-66vd2mdu 1878 1 The the DT cord-014597-66vd2mdu 1878 2 number number NN cord-014597-66vd2mdu 1878 3 of of IN cord-014597-66vd2mdu 1878 4 viable viable JJ cord-014597-66vd2mdu 1878 5 cells cell NNS cord-014597-66vd2mdu 1878 6 and and CC cord-014597-66vd2mdu 1878 7 GFP gfp NN cord-014597-66vd2mdu 1878 8 - - HYPH cord-014597-66vd2mdu 1878 9 positive positive JJ cord-014597-66vd2mdu 1878 10 cells cell NNS cord-014597-66vd2mdu 1878 11 were be VBD cord-014597-66vd2mdu 1878 12 counted count VBN cord-014597-66vd2mdu 1878 13 using use VBG cord-014597-66vd2mdu 1878 14 Countess Countess NNP cord-014597-66vd2mdu 1878 15 II II NNP cord-014597-66vd2mdu 1878 16 FL FL NNP cord-014597-66vd2mdu 1878 17 Automated Automated NNP cord-014597-66vd2mdu 1878 18 Cell Cell NNP cord-014597-66vd2mdu 1878 19 Counter Counter NNP cord-014597-66vd2mdu 1878 20 ( ( -LRB- cord-014597-66vd2mdu 1878 21 Thermo Thermo NNP cord-014597-66vd2mdu 1878 22 Fisher Fisher NNP cord-014597-66vd2mdu 1878 23 Scientific Scientific NNP cord-014597-66vd2mdu 1878 24 ) ) -RRB- cord-014597-66vd2mdu 1878 25 . . . cord-014597-66vd2mdu 1879 1 The the DT cord-014597-66vd2mdu 1879 2 transfected transfecte VBN cord-014597-66vd2mdu 1879 3 cells cell NNS cord-014597-66vd2mdu 1879 4 were be VBD cord-014597-66vd2mdu 1879 5 cultured culture VBN cord-014597-66vd2mdu 1879 6 in in IN cord-014597-66vd2mdu 1879 7 CELLSTAR CELLSTAR NNP cord-014597-66vd2mdu 1879 8 CELLreactor CELLreactor NNP cord-014597-66vd2mdu 1879 9 tubes tube NNS cord-014597-66vd2mdu 1879 10 . . . cord-014597-66vd2mdu 1880 1 The the DT cord-014597-66vd2mdu 1880 2 tubes tube NNS cord-014597-66vd2mdu 1880 3 were be VBD cord-014597-66vd2mdu 1880 4 incubated incubate VBN cord-014597-66vd2mdu 1880 5 in in IN cord-014597-66vd2mdu 1880 6 a a DT cord-014597-66vd2mdu 1880 7 Climo Climo NNP cord-014597-66vd2mdu 1880 8 - - HYPH cord-014597-66vd2mdu 1880 9 shaker shaker NN cord-014597-66vd2mdu 1880 10 ISF1-X ISF1-X NNP cord-014597-66vd2mdu 1880 11 ( ( -LRB- cord-014597-66vd2mdu 1880 12 Kuhner Kuhner NNP cord-014597-66vd2mdu 1880 13 ) ) -RRB- cord-014597-66vd2mdu 1880 14 . . . cord-014597-66vd2mdu 1881 1 Antibody antibody NN cord-014597-66vd2mdu 1881 2 production production NN cord-014597-66vd2mdu 1881 3 was be VBD cord-014597-66vd2mdu 1881 4 measured measure VBN cord-014597-66vd2mdu 1881 5 using use VBG cord-014597-66vd2mdu 1881 6 biolayer biolayer NN cord-014597-66vd2mdu 1881 7 interferometry interferometry NN cord-014597-66vd2mdu 1881 8 with with IN cord-014597-66vd2mdu 1881 9 an an DT cord-014597-66vd2mdu 1881 10 Octet octet NN cord-014597-66vd2mdu 1881 11 QK QK NNP cord-014597-66vd2mdu 1881 12 system system NN cord-014597-66vd2mdu 1881 13 ( ( -LRB- cord-014597-66vd2mdu 1881 14 Fortebio Fortebio NNP cord-014597-66vd2mdu 1881 15 ) ) -RRB- cord-014597-66vd2mdu 1881 16 . . . cord-014597-66vd2mdu 1882 1 We -PRON- PRP cord-014597-66vd2mdu 1882 2 constructed construct VBD cord-014597-66vd2mdu 1882 3 four four CD cord-014597-66vd2mdu 1882 4 CHO CHO NNP cord-014597-66vd2mdu 1882 5 cell cell NN cord-014597-66vd2mdu 1882 6 lines line NNS cord-014597-66vd2mdu 1882 7 stably stably RB cord-014597-66vd2mdu 1882 8 expressing express VBG cord-014597-66vd2mdu 1882 9 EBNA1 EBNA1 NNS cord-014597-66vd2mdu 1882 10 , , , cord-014597-66vd2mdu 1882 11 termed term VBD cord-014597-66vd2mdu 1882 12 IgG1-EB01 IgG1-EB01 NNPS cord-014597-66vd2mdu 1882 13 to to IN cord-014597-66vd2mdu 1882 14 EB04 EB04 NNP cord-014597-66vd2mdu 1882 15 . . . cord-014597-66vd2mdu 1883 1 In in IN cord-014597-66vd2mdu 1883 2 capillary capillary JJ cord-014597-66vd2mdu 1883 3 electrophoresis electrophoresis NN cord-014597-66vd2mdu 1883 4 analysis analysis NN cord-014597-66vd2mdu 1883 5 , , , cord-014597-66vd2mdu 1883 6 we -PRON- PRP cord-014597-66vd2mdu 1883 7 observed observe VBD cord-014597-66vd2mdu 1883 8 a a DT cord-014597-66vd2mdu 1883 9 clear clear JJ cord-014597-66vd2mdu 1883 10 peak peak NN cord-014597-66vd2mdu 1883 11 corresponding correspond VBG cord-014597-66vd2mdu 1883 12 to to IN cord-014597-66vd2mdu 1883 13 the the DT cord-014597-66vd2mdu 1883 14 EBNA1 EBNA1 NNS cord-014597-66vd2mdu 1883 15 expression expression NN cord-014597-66vd2mdu 1883 16 in in IN cord-014597-66vd2mdu 1883 17 all all DT cord-014597-66vd2mdu 1883 18 four four CD cord-014597-66vd2mdu 1883 19 cell cell NN cord-014597-66vd2mdu 1883 20 lines line NNS cord-014597-66vd2mdu 1883 21 . . . cord-014597-66vd2mdu 1884 1 We -PRON- PRP cord-014597-66vd2mdu 1884 2 tested test VBD cord-014597-66vd2mdu 1884 3 the the DT cord-014597-66vd2mdu 1884 4 transfection transfection NN cord-014597-66vd2mdu 1884 5 efficiency efficiency NN cord-014597-66vd2mdu 1884 6 by by IN cord-014597-66vd2mdu 1884 7 pOTC pOTC NNS cord-014597-66vd2mdu 1884 8 - - HYPH cord-014597-66vd2mdu 1884 9 GFP gfp NN cord-014597-66vd2mdu 1884 10 plasmids plasmid NNS cord-014597-66vd2mdu 1884 11 . . . cord-014597-66vd2mdu 1885 1 In in IN cord-014597-66vd2mdu 1885 2 the the DT cord-014597-66vd2mdu 1885 3 best good JJS cord-014597-66vd2mdu 1885 4 transfection transfection NN cord-014597-66vd2mdu 1885 5 condition condition NN cord-014597-66vd2mdu 1885 6 , , , cord-014597-66vd2mdu 1885 7 PEI PEI NNP cord-014597-66vd2mdu 1885 8 / / SYM cord-014597-66vd2mdu 1885 9 DNA dna NN cord-014597-66vd2mdu 1885 10 ratio ratio NN cord-014597-66vd2mdu 1885 11 of of IN cord-014597-66vd2mdu 1885 12 1/1 1/1 CD cord-014597-66vd2mdu 1885 13 , , , cord-014597-66vd2mdu 1885 14 IgG1-EB01 IgG1-EB01 NNP cord-014597-66vd2mdu 1885 15 cell cell NN cord-014597-66vd2mdu 1885 16 showed show VBD cord-014597-66vd2mdu 1885 17 the the DT cord-014597-66vd2mdu 1885 18 highest high JJS cord-014597-66vd2mdu 1885 19 GFP gfp NN cord-014597-66vd2mdu 1885 20 - - HYPH cord-014597-66vd2mdu 1885 21 positive positive JJ cord-014597-66vd2mdu 1885 22 cell cell NN cord-014597-66vd2mdu 1885 23 number number NN cord-014597-66vd2mdu 1885 24 ( ( -LRB- cord-014597-66vd2mdu 1885 25 1.07×10 1.07×10 CD cord-014597-66vd2mdu 1885 26 7 7 CD cord-014597-66vd2mdu 1885 27 cell cell NN cord-014597-66vd2mdu 1885 28 / / SYM cord-014597-66vd2mdu 1885 29 mL ml NN cord-014597-66vd2mdu 1885 30 ) ) -RRB- cord-014597-66vd2mdu 1885 31 and and CC cord-014597-66vd2mdu 1885 32 transfection transfection NN cord-014597-66vd2mdu 1885 33 efficiency efficiency NN cord-014597-66vd2mdu 1885 34 ( ( -LRB- cord-014597-66vd2mdu 1885 35 95 95 CD cord-014597-66vd2mdu 1885 36 % % NN cord-014597-66vd2mdu 1885 37 ) ) -RRB- cord-014597-66vd2mdu 1885 38 among among IN cord-014597-66vd2mdu 1885 39 the the DT cord-014597-66vd2mdu 1885 40 four four CD cord-014597-66vd2mdu 1885 41 cell cell NN cord-014597-66vd2mdu 1885 42 lines line NNS cord-014597-66vd2mdu 1885 43 . . . cord-014597-66vd2mdu 1886 1 Therefore therefore RB cord-014597-66vd2mdu 1886 2 , , , cord-014597-66vd2mdu 1886 3 IgG1-EB01 IgG1-EB01 NNP cord-014597-66vd2mdu 1886 4 cell cell NN cord-014597-66vd2mdu 1886 5 lines line NNS cord-014597-66vd2mdu 1886 6 were be VBD cord-014597-66vd2mdu 1886 7 selected select VBN cord-014597-66vd2mdu 1886 8 for for IN cord-014597-66vd2mdu 1886 9 further further JJ cord-014597-66vd2mdu 1886 10 study study NN cord-014597-66vd2mdu 1886 11 . . . cord-014597-66vd2mdu 1887 1 After after IN cord-014597-66vd2mdu 1887 2 the the DT cord-014597-66vd2mdu 1887 3 transfection transfection NN cord-014597-66vd2mdu 1887 4 , , , cord-014597-66vd2mdu 1887 5 the the DT cord-014597-66vd2mdu 1887 6 number number NN cord-014597-66vd2mdu 1887 7 of of IN cord-014597-66vd2mdu 1887 8 GFP gfp NN cord-014597-66vd2mdu 1887 9 - - HYPH cord-014597-66vd2mdu 1887 10 positive positive JJ cord-014597-66vd2mdu 1887 11 cells cell NNS cord-014597-66vd2mdu 1887 12 continued continue VBD cord-014597-66vd2mdu 1887 13 to to TO cord-014597-66vd2mdu 1887 14 increase increase VB cord-014597-66vd2mdu 1887 15 even even RB cord-014597-66vd2mdu 1887 16 after after IN cord-014597-66vd2mdu 1887 17 the the DT cord-014597-66vd2mdu 1887 18 passage passage NN cord-014597-66vd2mdu 1887 19 ( ( -LRB- cord-014597-66vd2mdu 1887 20 Fig Fig NNP cord-014597-66vd2mdu 1887 21 . . . cord-014597-66vd2mdu 1887 22 1 1 CD cord-014597-66vd2mdu 1887 23 ) ) -RRB- cord-014597-66vd2mdu 1887 24 , , , cord-014597-66vd2mdu 1887 25 suggesting suggest VBG cord-014597-66vd2mdu 1887 26 that that IN cord-014597-66vd2mdu 1887 27 the the DT cord-014597-66vd2mdu 1887 28 pOTC potc CD cord-014597-66vd2mdu 1887 29 - - HYPH cord-014597-66vd2mdu 1887 30 GFP gfp NN cord-014597-66vd2mdu 1887 31 plasmid plasmid NN cord-014597-66vd2mdu 1887 32 was be VBD cord-014597-66vd2mdu 1887 33 stably stably RB cord-014597-66vd2mdu 1887 34 retained retain VBN cord-014597-66vd2mdu 1887 35 and and CC cord-014597-66vd2mdu 1887 36 replicated replicate VBN cord-014597-66vd2mdu 1887 37 by by IN cord-014597-66vd2mdu 1887 38 EBNA1 EBNA1 NNP cord-014597-66vd2mdu 1887 39 / / SYM cord-014597-66vd2mdu 1887 40 oriP orip CD cord-014597-66vd2mdu 1887 41 system system NN cord-014597-66vd2mdu 1887 42 in in IN cord-014597-66vd2mdu 1887 43 IgG1-EB01 IgG1-EB01 NNP cord-014597-66vd2mdu 1887 44 cell cell NN cord-014597-66vd2mdu 1887 45 lines line NNS cord-014597-66vd2mdu 1887 46 . . . cord-014597-66vd2mdu 1888 1 In in IN cord-014597-66vd2mdu 1888 2 preliminary preliminary JJ cord-014597-66vd2mdu 1888 3 experiments experiment NNS cord-014597-66vd2mdu 1888 4 , , , cord-014597-66vd2mdu 1888 5 we -PRON- PRP cord-014597-66vd2mdu 1888 6 introduced introduce VBD cord-014597-66vd2mdu 1888 7 three three CD cord-014597-66vd2mdu 1888 8 genes gene NNS cord-014597-66vd2mdu 1888 9 , , , cord-014597-66vd2mdu 1888 10 MDH2 MDH2 NNP cord-014597-66vd2mdu 1888 11 , , , cord-014597-66vd2mdu 1888 12 GSS GSS NNP cord-014597-66vd2mdu 1888 13 and and CC cord-014597-66vd2mdu 1888 14 GCLM GCLM NNP cord-014597-66vd2mdu 1888 15 , , , cord-014597-66vd2mdu 1888 16 into into IN cord-014597-66vd2mdu 1888 17 IgG1-EB01 IgG1-EB01 NNP cord-014597-66vd2mdu 1888 18 cell cell NN cord-014597-66vd2mdu 1888 19 lines line NNS cord-014597-66vd2mdu 1888 20 . . . cord-014597-66vd2mdu 1889 1 Cotransfection cotransfection NN cord-014597-66vd2mdu 1889 2 of of IN cord-014597-66vd2mdu 1889 3 these these DT cord-014597-66vd2mdu 1889 4 three three CD cord-014597-66vd2mdu 1889 5 genes gene NNS cord-014597-66vd2mdu 1889 6 led lead VBD cord-014597-66vd2mdu 1889 7 to to IN cord-014597-66vd2mdu 1889 8 an an DT cord-014597-66vd2mdu 1889 9 increase increase NN cord-014597-66vd2mdu 1889 10 in in IN cord-014597-66vd2mdu 1889 11 IgG1 igg1 CD cord-014597-66vd2mdu 1889 12 production production NN cord-014597-66vd2mdu 1889 13 from from IN cord-014597-66vd2mdu 1889 14 287±18 287±18 CD cord-014597-66vd2mdu 1889 15 mg mg NNP cord-014597-66vd2mdu 1889 16 / / SYM cord-014597-66vd2mdu 1889 17 L L NNP cord-014597-66vd2mdu 1889 18 ( ( -LRB- cord-014597-66vd2mdu 1889 19 control control NN cord-014597-66vd2mdu 1889 20 ) ) -RRB- cord-014597-66vd2mdu 1889 21 to to IN cord-014597-66vd2mdu 1889 22 334±21 334±21 CD cord-014597-66vd2mdu 1889 23 mg mg NNP cord-014597-66vd2mdu 1889 24 / / SYM cord-014597-66vd2mdu 1889 25 L L NNP cord-014597-66vd2mdu 1889 26 at at IN cord-014597-66vd2mdu 1889 27 day day NN cord-014597-66vd2mdu 1889 28 8 8 CD cord-014597-66vd2mdu 1889 29 ( ( -LRB- cord-014597-66vd2mdu 1889 30 P<0.05 P<0.05 NNS cord-014597-66vd2mdu 1889 31 , , , cord-014597-66vd2mdu 1889 32 t t NN cord-014597-66vd2mdu 1889 33 - - HYPH cord-014597-66vd2mdu 1889 34 test test NN cord-014597-66vd2mdu 1889 35 , , , cord-014597-66vd2mdu 1889 36 n=3 n=3 NN cord-014597-66vd2mdu 1889 37 ) ) -RRB- cord-014597-66vd2mdu 1889 38 . . . cord-014597-66vd2mdu 1890 1 This this DT cord-014597-66vd2mdu 1890 2 result result NN cord-014597-66vd2mdu 1890 3 suggests suggest VBZ cord-014597-66vd2mdu 1890 4 that that IN cord-014597-66vd2mdu 1890 5 these these DT cord-014597-66vd2mdu 1890 6 three three CD cord-014597-66vd2mdu 1890 7 genes gene NNS cord-014597-66vd2mdu 1890 8 work work VBP cord-014597-66vd2mdu 1890 9 as as IN cord-014597-66vd2mdu 1890 10 production production NN cord-014597-66vd2mdu 1890 11 enhancer enhancer NN cord-014597-66vd2mdu 1890 12 genes gene NNS cord-014597-66vd2mdu 1890 13 . . . cord-014597-66vd2mdu 1891 1 Conventional conventional JJ cord-014597-66vd2mdu 1891 2 methods method NNS cord-014597-66vd2mdu 1891 3 based base VBN cord-014597-66vd2mdu 1891 4 on on IN cord-014597-66vd2mdu 1891 5 stable stable JJ cord-014597-66vd2mdu 1891 6 cells cell NNS cord-014597-66vd2mdu 1891 7 take take VBP cord-014597-66vd2mdu 1891 8 up up IN cord-014597-66vd2mdu 1891 9 to to TO cord-014597-66vd2mdu 1891 10 6 6 CD cord-014597-66vd2mdu 1891 11 months month NNS cord-014597-66vd2mdu 1891 12 to to TO cord-014597-66vd2mdu 1891 13 determine determine VB cord-014597-66vd2mdu 1891 14 whether whether IN cord-014597-66vd2mdu 1891 15 the the DT cord-014597-66vd2mdu 1891 16 gene gene NN cord-014597-66vd2mdu 1891 17 of of IN cord-014597-66vd2mdu 1891 18 interest interest NN cord-014597-66vd2mdu 1891 19 is be VBZ cord-014597-66vd2mdu 1891 20 beneficial beneficial JJ cord-014597-66vd2mdu 1891 21 for for IN cord-014597-66vd2mdu 1891 22 recombinant recombinant JJ cord-014597-66vd2mdu 1891 23 IgG1 igg1 CD cord-014597-66vd2mdu 1891 24 production production NN cord-014597-66vd2mdu 1891 25 . . . cord-014597-66vd2mdu 1892 1 In in IN cord-014597-66vd2mdu 1892 2 contrast contrast NN cord-014597-66vd2mdu 1892 3 , , , cord-014597-66vd2mdu 1892 4 identification identification NN cord-014597-66vd2mdu 1892 5 of of IN cord-014597-66vd2mdu 1892 6 production production NN cord-014597-66vd2mdu 1892 7 enhancer enhancer NN cord-014597-66vd2mdu 1892 8 genes gene NNS cord-014597-66vd2mdu 1892 9 is be VBZ cord-014597-66vd2mdu 1892 10 achievable achievable JJ cord-014597-66vd2mdu 1892 11 within within IN cord-014597-66vd2mdu 1892 12 10 10 CD cord-014597-66vd2mdu 1892 13 days day NNS cord-014597-66vd2mdu 1892 14 by by IN cord-014597-66vd2mdu 1892 15 our -PRON- PRP$ cord-014597-66vd2mdu 1892 16 proposed propose VBN cord-014597-66vd2mdu 1892 17 method method NN cord-014597-66vd2mdu 1892 18 based base VBN cord-014597-66vd2mdu 1892 19 on on IN cord-014597-66vd2mdu 1892 20 EBNA1 EBNA1 NNS cord-014597-66vd2mdu 1892 21 / / SYM cord-014597-66vd2mdu 1892 22 oriP orip CD cord-014597-66vd2mdu 1892 23 system system NN cord-014597-66vd2mdu 1892 24 . . . cord-014597-66vd2mdu 1893 1 The the DT cord-014597-66vd2mdu 1893 2 proposed propose VBN cord-014597-66vd2mdu 1893 3 method method NN cord-014597-66vd2mdu 1893 4 makes make VBZ cord-014597-66vd2mdu 1893 5 it -PRON- PRP cord-014597-66vd2mdu 1893 6 possible possible JJ cord-014597-66vd2mdu 1893 7 to to TO cord-014597-66vd2mdu 1893 8 evaluate evaluate VB cord-014597-66vd2mdu 1893 9 production production NN cord-014597-66vd2mdu 1893 10 enhancer enhancer NN cord-014597-66vd2mdu 1893 11 genes gene NNS cord-014597-66vd2mdu 1893 12 in in IN cord-014597-66vd2mdu 1893 13 a a DT cord-014597-66vd2mdu 1893 14 rapid rapid JJ cord-014597-66vd2mdu 1893 15 manner manner NN cord-014597-66vd2mdu 1893 16 . . . cord-014597-66vd2mdu 1894 1 The the DT cord-014597-66vd2mdu 1894 2 proposed propose VBN cord-014597-66vd2mdu 1894 3 method method NN cord-014597-66vd2mdu 1894 4 is be VBZ cord-014597-66vd2mdu 1894 5 a a DT cord-014597-66vd2mdu 1894 6 promising promising JJ cord-014597-66vd2mdu 1894 7 approach approach NN cord-014597-66vd2mdu 1894 8 to to TO cord-014597-66vd2mdu 1894 9 identify identify VB cord-014597-66vd2mdu 1894 10 genes gene NNS cord-014597-66vd2mdu 1894 11 enhancing enhance VBG cord-014597-66vd2mdu 1894 12 recombinant recombinant JJ cord-014597-66vd2mdu 1894 13 antibody antibody NN cord-014597-66vd2mdu 1894 14 production production NN cord-014597-66vd2mdu 1894 15 . . . cord-014597-66vd2mdu 1895 1 Background background NN cord-014597-66vd2mdu 1895 2 2 2 CD cord-014597-66vd2mdu 1895 3 G G NNP cord-014597-66vd2mdu 1895 4 UNic UNic NNP cord-014597-66vd2mdu 1895 5 ™ ™ NN cord-014597-66vd2mdu 1895 6 ( ( -LRB- cord-014597-66vd2mdu 1895 7 2GUN 2gun LS cord-014597-66vd2mdu 1895 8 ) ) -RRB- cord-014597-66vd2mdu 1895 9 technology technology NN cord-014597-66vd2mdu 1895 10 comprises comprise VBZ cord-014597-66vd2mdu 1895 11 a a DT cord-014597-66vd2mdu 1895 12 set set NN cord-014597-66vd2mdu 1895 13 of of IN cord-014597-66vd2mdu 1895 14 protected protect VBN cord-014597-66vd2mdu 1895 15 genetic genetic JJ cord-014597-66vd2mdu 1895 16 elements element NNS cord-014597-66vd2mdu 1895 17 that that WDT cord-014597-66vd2mdu 1895 18 improve improve VBP cord-014597-66vd2mdu 1895 19 protein protein NN cord-014597-66vd2mdu 1895 20 production production NN cord-014597-66vd2mdu 1895 21 by by IN cord-014597-66vd2mdu 1895 22 acting act VBG cord-014597-66vd2mdu 1895 23 on on IN cord-014597-66vd2mdu 1895 24 transcription transcription NN cord-014597-66vd2mdu 1895 25 as as RB cord-014597-66vd2mdu 1895 26 well well RB cord-014597-66vd2mdu 1895 27 as as IN cord-014597-66vd2mdu 1895 28 on on IN cord-014597-66vd2mdu 1895 29 translation translation NN cord-014597-66vd2mdu 1895 30 . . . cord-014597-66vd2mdu 1896 1 The the DT cord-014597-66vd2mdu 1896 2 elements element NNS cord-014597-66vd2mdu 1896 3 can can MD cord-014597-66vd2mdu 1896 4 either either CC cord-014597-66vd2mdu 1896 5 be be VB cord-014597-66vd2mdu 1896 6 inserted insert VBN cord-014597-66vd2mdu 1896 7 into into IN cord-014597-66vd2mdu 1896 8 existing exist VBG cord-014597-66vd2mdu 1896 9 ( ( -LRB- cord-014597-66vd2mdu 1896 10 platform platform NN cord-014597-66vd2mdu 1896 11 ) ) -RRB- cord-014597-66vd2mdu 1896 12 vectors vector NNS cord-014597-66vd2mdu 1896 13 or or CC cord-014597-66vd2mdu 1896 14 be be VB cord-014597-66vd2mdu 1896 15 provided provide VBN cord-014597-66vd2mdu 1896 16 as as IN cord-014597-66vd2mdu 1896 17 complete complete JJ cord-014597-66vd2mdu 1896 18 ready ready JJ cord-014597-66vd2mdu 1896 19 - - HYPH cord-014597-66vd2mdu 1896 20 to to IN cord-014597-66vd2mdu 1896 21 - - HYPH cord-014597-66vd2mdu 1896 22 use use NN cord-014597-66vd2mdu 1896 23 vectors vector NNS cord-014597-66vd2mdu 1896 24 . . . cord-014597-66vd2mdu 1897 1 The the DT cord-014597-66vd2mdu 1897 2 technology technology NN cord-014597-66vd2mdu 1897 3 can can MD cord-014597-66vd2mdu 1897 4 be be VB cord-014597-66vd2mdu 1897 5 used use VBN cord-014597-66vd2mdu 1897 6 in in IN cord-014597-66vd2mdu 1897 7 stable stable JJ cord-014597-66vd2mdu 1897 8 and and CC cord-014597-66vd2mdu 1897 9 in in IN cord-014597-66vd2mdu 1897 10 transient transient JJ cord-014597-66vd2mdu 1897 11 transfection transfection NN cord-014597-66vd2mdu 1897 12 to to TO cord-014597-66vd2mdu 1897 13 boost boost VB cord-014597-66vd2mdu 1897 14 protein protein NN cord-014597-66vd2mdu 1897 15 production production NN cord-014597-66vd2mdu 1897 16 for for IN cord-014597-66vd2mdu 1897 17 product product NN cord-014597-66vd2mdu 1897 18 development development NN cord-014597-66vd2mdu 1897 19 and and CC cord-014597-66vd2mdu 1897 20 is be VBZ cord-014597-66vd2mdu 1897 21 being be VBG cord-014597-66vd2mdu 1897 22 applied apply VBN cord-014597-66vd2mdu 1897 23 in in IN cord-014597-66vd2mdu 1897 24 CLD CLD NNP cord-014597-66vd2mdu 1897 25 for for IN cord-014597-66vd2mdu 1897 26 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 1897 27 proteins protein NNS cord-014597-66vd2mdu 1897 28 . . . cord-014597-66vd2mdu 1898 1 In in IN cord-014597-66vd2mdu 1898 2 combination combination NN cord-014597-66vd2mdu 1898 3 with with IN cord-014597-66vd2mdu 1898 4 antibiotic antibiotic JJ cord-014597-66vd2mdu 1898 5 selection selection NN cord-014597-66vd2mdu 1898 6 or or CC cord-014597-66vd2mdu 1898 7 DHFR DHFR NNP cord-014597-66vd2mdu 1898 8 selection selection NN cord-014597-66vd2mdu 1898 9 , , , cord-014597-66vd2mdu 1898 10 2GUN 2GUN NNP cord-014597-66vd2mdu 1898 11 technology technology NN cord-014597-66vd2mdu 1898 12 routinely routinely RB cord-014597-66vd2mdu 1898 13 results result VBZ cord-014597-66vd2mdu 1898 14 in in IN cord-014597-66vd2mdu 1898 15 2 2 CD cord-014597-66vd2mdu 1898 16 - - SYM cord-014597-66vd2mdu 1898 17 3 3 CD cord-014597-66vd2mdu 1898 18 fold fold VB cord-014597-66vd2mdu 1898 19 increase increase NN cord-014597-66vd2mdu 1898 20 in in IN cord-014597-66vd2mdu 1898 21 expression expression NN cord-014597-66vd2mdu 1898 22 of of IN cord-014597-66vd2mdu 1898 23 client client NN cord-014597-66vd2mdu 1898 24 antibodies antibody NNS cord-014597-66vd2mdu 1898 25 or or CC cord-014597-66vd2mdu 1898 26 fusion fusion NN cord-014597-66vd2mdu 1898 27 proteins protein NNS cord-014597-66vd2mdu 1898 28 , , , cord-014597-66vd2mdu 1898 29 both both CC cord-014597-66vd2mdu 1898 30 in in IN cord-014597-66vd2mdu 1898 31 pools pool NNS cord-014597-66vd2mdu 1898 32 and and CC cord-014597-66vd2mdu 1898 33 after after IN cord-014597-66vd2mdu 1898 34 clonal clonal JJ cord-014597-66vd2mdu 1898 35 selection selection NN cord-014597-66vd2mdu 1898 36 . . . cord-014597-66vd2mdu 1899 1 Previously previously RB cord-014597-66vd2mdu 1899 2 , , , cord-014597-66vd2mdu 1899 3 we -PRON- PRP cord-014597-66vd2mdu 1899 4 have have VBP cord-014597-66vd2mdu 1899 5 successfully successfully RB cord-014597-66vd2mdu 1899 6 combined combine VBN cord-014597-66vd2mdu 1899 7 2GUN 2gun CD cord-014597-66vd2mdu 1899 8 technology technology NN cord-014597-66vd2mdu 1899 9 with with IN cord-014597-66vd2mdu 1899 10 glutamine glutamine NN cord-014597-66vd2mdu 1899 11 synthetase synthetase NN cord-014597-66vd2mdu 1899 12 ( ( -LRB- cord-014597-66vd2mdu 1899 13 GS GS NNP cord-014597-66vd2mdu 1899 14 ) ) -RRB- cord-014597-66vd2mdu 1899 15 selection selection NN cord-014597-66vd2mdu 1899 16 and and CC cord-014597-66vd2mdu 1899 17 the the DT cord-014597-66vd2mdu 1899 18 CHO CHO NNP cord-014597-66vd2mdu 1899 19 GS GS NNP cord-014597-66vd2mdu 1899 20 null null NN cord-014597-66vd2mdu 1899 21 cells cell NNS cord-014597-66vd2mdu 1899 22 of of IN cord-014597-66vd2mdu 1899 23 Horizon Horizon NNP cord-014597-66vd2mdu 1899 24 Discovery Discovery NNP cord-014597-66vd2mdu 1899 25 , , , cord-014597-66vd2mdu 1899 26 resulting result VBG cord-014597-66vd2mdu 1899 27 in in IN cord-014597-66vd2mdu 1899 28 clonal clonal JJ cord-014597-66vd2mdu 1899 29 cell cell NN cord-014597-66vd2mdu 1899 30 lines line NNS cord-014597-66vd2mdu 1899 31 producing produce VBG cord-014597-66vd2mdu 1899 32 > > XX cord-014597-66vd2mdu 1900 1 6 6 CD cord-014597-66vd2mdu 1900 2 g g NN cord-014597-66vd2mdu 1900 3 / / SYM cord-014597-66vd2mdu 1900 4 L l NN cord-014597-66vd2mdu 1900 5 of of IN cord-014597-66vd2mdu 1900 6 a a DT cord-014597-66vd2mdu 1900 7 biosimilar biosimilar NNP cord-014597-66vd2mdu 1900 8 mAb mab NN cord-014597-66vd2mdu 1900 9 in in IN cord-014597-66vd2mdu 1900 10 fed fed NNP cord-014597-66vd2mdu 1900 11 - - HYPH cord-014597-66vd2mdu 1900 12 batch batch NN cord-014597-66vd2mdu 1900 13 assay assay NN cord-014597-66vd2mdu 1900 14 . . . cord-014597-66vd2mdu 1901 1 Here here RB cord-014597-66vd2mdu 1901 2 we -PRON- PRP cord-014597-66vd2mdu 1901 3 present present VBP cord-014597-66vd2mdu 1901 4 data datum NNS cord-014597-66vd2mdu 1901 5 on on IN cord-014597-66vd2mdu 1901 6 the the DT cord-014597-66vd2mdu 1901 7 successful successful JJ cord-014597-66vd2mdu 1901 8 application application NN cord-014597-66vd2mdu 1901 9 of of IN cord-014597-66vd2mdu 1901 10 the the DT cord-014597-66vd2mdu 1901 11 2GUN 2GUN NNP cord-014597-66vd2mdu 1901 12 technology technology NN cord-014597-66vd2mdu 1901 13 for for IN cord-014597-66vd2mdu 1901 14 the the DT cord-014597-66vd2mdu 1901 15 enhanced enhanced JJ cord-014597-66vd2mdu 1901 16 expression expression NN cord-014597-66vd2mdu 1901 17 of of IN cord-014597-66vd2mdu 1901 18 a a DT cord-014597-66vd2mdu 1901 19 large large JJ cord-014597-66vd2mdu 1901 20 ( ( -LRB- cord-014597-66vd2mdu 1901 21 > > NFP cord-014597-66vd2mdu 1901 22 300 300 CD cord-014597-66vd2mdu 1901 23 kDa kDa NNPS cord-014597-66vd2mdu 1901 24 ) ) -RRB- cord-014597-66vd2mdu 1901 25 human human JJ cord-014597-66vd2mdu 1901 26 heterotrimeric heterotrimeric NNP cord-014597-66vd2mdu 1901 27 glycoprotein glycoprotein NN cord-014597-66vd2mdu 1901 28 , , , cord-014597-66vd2mdu 1901 29 a a DT cord-014597-66vd2mdu 1901 30 renowned renowned JJ cord-014597-66vd2mdu 1901 31 difficult difficult JJ cord-014597-66vd2mdu 1901 32 - - HYPH cord-014597-66vd2mdu 1901 33 to to TO cord-014597-66vd2mdu 1901 34 - - HYPH cord-014597-66vd2mdu 1901 35 express express VB cord-014597-66vd2mdu 1901 36 ( ( -LRB- cord-014597-66vd2mdu 1901 37 DTE DTE NNP cord-014597-66vd2mdu 1901 38 ) ) -RRB- cord-014597-66vd2mdu 1901 39 protein protein NN cord-014597-66vd2mdu 1901 40 . . . cord-014597-66vd2mdu 1902 1 All all DT cord-014597-66vd2mdu 1902 2 expression expression NN cord-014597-66vd2mdu 1902 3 vectors vector NNS cord-014597-66vd2mdu 1902 4 comprised comprise VBD cord-014597-66vd2mdu 1902 5 a a DT cord-014597-66vd2mdu 1902 6 hCMV hcmv NN cord-014597-66vd2mdu 1902 7 promoter promoter NN cord-014597-66vd2mdu 1902 8 and and CC cord-014597-66vd2mdu 1902 9 BGH BGH NNP cord-014597-66vd2mdu 1902 10 polyadenylation polyadenylation NN cord-014597-66vd2mdu 1902 11 sequence sequence NN cord-014597-66vd2mdu 1902 12 in in IN cord-014597-66vd2mdu 1902 13 the the DT cord-014597-66vd2mdu 1902 14 expression expression NN cord-014597-66vd2mdu 1902 15 cassettes cassette NNS cord-014597-66vd2mdu 1902 16 for for IN cord-014597-66vd2mdu 1902 17 the the DT cord-014597-66vd2mdu 1902 18 gene gene NN cord-014597-66vd2mdu 1902 19 of of IN cord-014597-66vd2mdu 1902 20 interest interest NN cord-014597-66vd2mdu 1902 21 , , , cord-014597-66vd2mdu 1902 22 and and CC cord-014597-66vd2mdu 1902 23 a a DT cord-014597-66vd2mdu 1902 24 selection selection NN cord-014597-66vd2mdu 1902 25 marker marker NN cord-014597-66vd2mdu 1902 26 gene gene NN cord-014597-66vd2mdu 1902 27 with with IN cord-014597-66vd2mdu 1902 28 SV40 SV40 NNP cord-014597-66vd2mdu 1902 29 promoter promoter NN cord-014597-66vd2mdu 1902 30 and and CC cord-014597-66vd2mdu 1902 31 SV40 SV40 NNP cord-014597-66vd2mdu 1902 32 polyadenylation polyadenylation NN cord-014597-66vd2mdu 1902 33 sequence sequence NN cord-014597-66vd2mdu 1902 34 . . . cord-014597-66vd2mdu 1903 1 2 2 LS cord-014597-66vd2mdu 1903 2 G G NNP cord-014597-66vd2mdu 1903 3 UNic UNic NNP cord-014597-66vd2mdu 1903 4 ™ ™ NN cord-014597-66vd2mdu 1903 5 Vectors Vectors NNP cord-014597-66vd2mdu 1903 6 also also RB cord-014597-66vd2mdu 1903 7 contained contain VBD cord-014597-66vd2mdu 1903 8 genetic genetic JJ cord-014597-66vd2mdu 1903 9 elements element NNS cord-014597-66vd2mdu 1903 10 ( ( -LRB- cord-014597-66vd2mdu 1903 11 2 2 CD cord-014597-66vd2mdu 1903 12 G G NNP cord-014597-66vd2mdu 1903 13 UNic UNic NNP cord-014597-66vd2mdu 1903 14 ™ ™ NN cord-014597-66vd2mdu 1903 15 technology technology NN cord-014597-66vd2mdu 1903 16 , , , cord-014597-66vd2mdu 1903 17 ProteoNic ProteoNic NNP cord-014597-66vd2mdu 1903 18 ) ) -RRB- cord-014597-66vd2mdu 1903 19 . . . cord-014597-66vd2mdu 1904 1 CHO CHO NNP cord-014597-66vd2mdu 1904 2 GS GS NNP cord-014597-66vd2mdu 1904 3 null null NN cord-014597-66vd2mdu 1904 4 cells cell NNS cord-014597-66vd2mdu 1904 5 ( ( -LRB- cord-014597-66vd2mdu 1904 6 Horizon Horizon NNP cord-014597-66vd2mdu 1904 7 Discovery Discovery NNP cord-014597-66vd2mdu 1904 8 ) ) -RRB- cord-014597-66vd2mdu 1904 9 were be VBD cord-014597-66vd2mdu 1904 10 transfected transfecte VBN cord-014597-66vd2mdu 1904 11 in in IN cord-014597-66vd2mdu 1904 12 duplicate duplicate NN cord-014597-66vd2mdu 1904 13 with with IN cord-014597-66vd2mdu 1904 14 Reference reference NN cord-014597-66vd2mdu 1904 15 or or CC cord-014597-66vd2mdu 1904 16 2GUN 2gun JJ cord-014597-66vd2mdu 1904 17 expression expression NN cord-014597-66vd2mdu 1904 18 vectors vector NNS cord-014597-66vd2mdu 1904 19 and and CC cord-014597-66vd2mdu 1904 20 selected select VBN cord-014597-66vd2mdu 1904 21 in in IN cord-014597-66vd2mdu 1904 22 media medium NNS cord-014597-66vd2mdu 1904 23 lacking lack VBG cord-014597-66vd2mdu 1904 24 glutamine glutamine NN cord-014597-66vd2mdu 1904 25 and and CC cord-014597-66vd2mdu 1904 26 containing contain VBG cord-014597-66vd2mdu 1904 27 the the DT cord-014597-66vd2mdu 1904 28 appropriate appropriate JJ cord-014597-66vd2mdu 1904 29 antibiotics antibiotic NNS cord-014597-66vd2mdu 1904 30 . . . cord-014597-66vd2mdu 1905 1 The the DT cord-014597-66vd2mdu 1905 2 bulk bulk JJ cord-014597-66vd2mdu 1905 3 pools pool NNS cord-014597-66vd2mdu 1905 4 were be VBD cord-014597-66vd2mdu 1905 5 seeded seed VBN cord-014597-66vd2mdu 1905 6 at at IN cord-014597-66vd2mdu 1905 7 equal equal JJ cord-014597-66vd2mdu 1905 8 viable viable JJ cord-014597-66vd2mdu 1905 9 cell cell NN cord-014597-66vd2mdu 1905 10 density density NN cord-014597-66vd2mdu 1905 11 after after IN cord-014597-66vd2mdu 1905 12 obtaining obtain VBG cord-014597-66vd2mdu 1905 13 maximum maximum JJ cord-014597-66vd2mdu 1905 14 viability viability NN cord-014597-66vd2mdu 1905 15 and and CC cord-014597-66vd2mdu 1905 16 cultured culture VBN cord-014597-66vd2mdu 1905 17 for for IN cord-014597-66vd2mdu 1905 18 9 9 CD cord-014597-66vd2mdu 1905 19 days day NNS cord-014597-66vd2mdu 1905 20 without without IN cord-014597-66vd2mdu 1905 21 feeding feed VBG cord-014597-66vd2mdu 1905 22 ( ( -LRB- cord-014597-66vd2mdu 1905 23 batch batch NN cord-014597-66vd2mdu 1905 24 ) ) -RRB- cord-014597-66vd2mdu 1905 25 . . . cord-014597-66vd2mdu 1906 1 Expression expression NN cord-014597-66vd2mdu 1906 2 of of IN cord-014597-66vd2mdu 1906 3 the the DT cord-014597-66vd2mdu 1906 4 target target NN cord-014597-66vd2mdu 1906 5 protein protein NN cord-014597-66vd2mdu 1906 6 in in IN cord-014597-66vd2mdu 1906 7 cell cell NN cord-014597-66vd2mdu 1906 8 culture culture NN cord-014597-66vd2mdu 1906 9 supernatants supernatant NNS cord-014597-66vd2mdu 1906 10 of of IN cord-014597-66vd2mdu 1906 11 stable stable JJ cord-014597-66vd2mdu 1906 12 bulk bulk JJ cord-014597-66vd2mdu 1906 13 pools pool NNS cord-014597-66vd2mdu 1906 14 was be VBD cord-014597-66vd2mdu 1906 15 measured measure VBN cord-014597-66vd2mdu 1906 16 by by IN cord-014597-66vd2mdu 1906 17 ELISA ELISA NNP cord-014597-66vd2mdu 1906 18 . . . cord-014597-66vd2mdu 1907 1 The the DT cord-014597-66vd2mdu 1907 2 three three CD cord-014597-66vd2mdu 1907 3 protein protein NN cord-014597-66vd2mdu 1907 4 subunit subunit NN cord-014597-66vd2mdu 1907 5 genes gene NNS cord-014597-66vd2mdu 1907 6 were be VBD cord-014597-66vd2mdu 1907 7 expressed express VBN cord-014597-66vd2mdu 1907 8 from from IN cord-014597-66vd2mdu 1907 9 vectors vector NNS cord-014597-66vd2mdu 1907 10 with with IN cord-014597-66vd2mdu 1907 11 different different JJ cord-014597-66vd2mdu 1907 12 selection selection NN cord-014597-66vd2mdu 1907 13 markers marker NNS cord-014597-66vd2mdu 1907 14 . . . cord-014597-66vd2mdu 1908 1 In in IN cord-014597-66vd2mdu 1908 2 the the DT cord-014597-66vd2mdu 1908 3 Reference reference NN cord-014597-66vd2mdu 1908 4 constructs construct NNS cord-014597-66vd2mdu 1908 5 ( ( -LRB- cord-014597-66vd2mdu 1908 6 without without IN cord-014597-66vd2mdu 1908 7 2GUN 2GUN NNP cord-014597-66vd2mdu 1908 8 ) ) -RRB- cord-014597-66vd2mdu 1908 9 , , , cord-014597-66vd2mdu 1908 10 the the DT cord-014597-66vd2mdu 1908 11 α α NNP cord-014597-66vd2mdu 1908 12 , , , cord-014597-66vd2mdu 1908 13 β β NN cord-014597-66vd2mdu 1908 14 , , , cord-014597-66vd2mdu 1908 15 and and CC cord-014597-66vd2mdu 1908 16 γ γ NN cord-014597-66vd2mdu 1908 17 chains chain NNS cord-014597-66vd2mdu 1908 18 were be VBD cord-014597-66vd2mdu 1908 19 expressed express VBN cord-014597-66vd2mdu 1908 20 from from IN cord-014597-66vd2mdu 1908 21 vectors vector NNS cord-014597-66vd2mdu 1908 22 with with IN cord-014597-66vd2mdu 1908 23 marker marker NN cord-014597-66vd2mdu 1908 24 genes gene NNS cord-014597-66vd2mdu 1908 25 for for IN cord-014597-66vd2mdu 1908 26 zeocin zeocin NNS cord-014597-66vd2mdu 1908 27 , , , cord-014597-66vd2mdu 1908 28 blasticidin blasticidin NNP cord-014597-66vd2mdu 1908 29 , , , cord-014597-66vd2mdu 1908 30 and and CC cord-014597-66vd2mdu 1908 31 GS GS NNP cord-014597-66vd2mdu 1908 32 , , , cord-014597-66vd2mdu 1908 33 respectively respectively RB cord-014597-66vd2mdu 1908 34 . . . cord-014597-66vd2mdu 1909 1 A a DT cord-014597-66vd2mdu 1909 2 similar similar JJ cord-014597-66vd2mdu 1909 3 3 3 CD cord-014597-66vd2mdu 1909 4 vector vector NN cord-014597-66vd2mdu 1909 5 combination combination NN cord-014597-66vd2mdu 1909 6 was be VBD cord-014597-66vd2mdu 1909 7 also also RB cord-014597-66vd2mdu 1909 8 generated generate VBN cord-014597-66vd2mdu 1909 9 with with IN cord-014597-66vd2mdu 1909 10 2GUN 2gun CD cord-014597-66vd2mdu 1909 11 elements element NNS cord-014597-66vd2mdu 1909 12 integrated integrate VBN cord-014597-66vd2mdu 1909 13 in in IN cord-014597-66vd2mdu 1909 14 each each DT cord-014597-66vd2mdu 1909 15 vector vector NN cord-014597-66vd2mdu 1909 16 . . . cord-014597-66vd2mdu 1910 1 In in IN cord-014597-66vd2mdu 1910 2 addition addition NN cord-014597-66vd2mdu 1910 3 , , , cord-014597-66vd2mdu 1910 4 2 2 CD cord-014597-66vd2mdu 1910 5 vectors vector NNS cord-014597-66vd2mdu 1910 6 with with IN cord-014597-66vd2mdu 1910 7 2 2 CD cord-014597-66vd2mdu 1910 8 subunits subunit NNS cord-014597-66vd2mdu 1910 9 ( ( -LRB- cord-014597-66vd2mdu 1910 10 γ γ NN cord-014597-66vd2mdu 1910 11 - - HYPH cord-014597-66vd2mdu 1910 12 α α NN cord-014597-66vd2mdu 1910 13 and and CC cord-014597-66vd2mdu 1910 14 α α NN cord-014597-66vd2mdu 1910 15 - - HYPH cord-014597-66vd2mdu 1910 16 γ γ NNP cord-014597-66vd2mdu 1910 17 ) ) -RRB- cord-014597-66vd2mdu 1910 18 , , , cord-014597-66vd2mdu 1910 19 each each DT cord-014597-66vd2mdu 1910 20 with with IN cord-014597-66vd2mdu 1910 21 a a DT cord-014597-66vd2mdu 1910 22 separate separate JJ cord-014597-66vd2mdu 1910 23 2GUN 2gun CD cord-014597-66vd2mdu 1910 24 element element NN cord-014597-66vd2mdu 1910 25 , , , cord-014597-66vd2mdu 1910 26 promoter promoter NN cord-014597-66vd2mdu 1910 27 and and CC cord-014597-66vd2mdu 1910 28 polyadenylation polyadenylation NN cord-014597-66vd2mdu 1910 29 signal signal NN cord-014597-66vd2mdu 1910 30 , , , cord-014597-66vd2mdu 1910 31 were be VBD cord-014597-66vd2mdu 1910 32 generated generate VBN cord-014597-66vd2mdu 1910 33 with with IN cord-014597-66vd2mdu 1910 34 a a DT cord-014597-66vd2mdu 1910 35 GS GS NNP cord-014597-66vd2mdu 1910 36 marker marker NN cord-014597-66vd2mdu 1910 37 gene gene NN cord-014597-66vd2mdu 1910 38 . . . cord-014597-66vd2mdu 1911 1 CHO CHO NNP cord-014597-66vd2mdu 1911 2 GS GS NNP cord-014597-66vd2mdu 1911 3 -/cells -/cells NNP cord-014597-66vd2mdu 1911 4 were be VBD cord-014597-66vd2mdu 1911 5 transfected transfecte VBN cord-014597-66vd2mdu 1911 6 with with IN cord-014597-66vd2mdu 1911 7 the the DT cord-014597-66vd2mdu 1911 8 4 4 CD cord-014597-66vd2mdu 1911 9 appropriate appropriate JJ cord-014597-66vd2mdu 1911 10 vector vector NN cord-014597-66vd2mdu 1911 11 combinations combination NNS cord-014597-66vd2mdu 1911 12 in in IN cord-014597-66vd2mdu 1911 13 equimolar equimolar JJ cord-014597-66vd2mdu 1911 14 ratios ratio NNS cord-014597-66vd2mdu 1911 15 and and CC cord-014597-66vd2mdu 1911 16 selected select VBN cord-014597-66vd2mdu 1911 17 in in IN cord-014597-66vd2mdu 1911 18 bulk bulk NN cord-014597-66vd2mdu 1911 19 in in IN cord-014597-66vd2mdu 1911 20 medium medium JJ cord-014597-66vd2mdu 1911 21 lacking lack VBG cord-014597-66vd2mdu 1911 22 glutamine glutamine NN cord-014597-66vd2mdu 1911 23 and and CC cord-014597-66vd2mdu 1911 24 1 1 CD cord-014597-66vd2mdu 1911 25 or or CC cord-014597-66vd2mdu 1911 26 2 2 CD cord-014597-66vd2mdu 1911 27 antibiotics antibiotic NNS cord-014597-66vd2mdu 1911 28 . . . cord-014597-66vd2mdu 1912 1 The the DT cord-014597-66vd2mdu 1912 2 2-vector 2-vector CD cord-014597-66vd2mdu 1912 3 transfected transfecte VBD cord-014597-66vd2mdu 1912 4 cell cell NN cord-014597-66vd2mdu 1912 5 pools pool NNS cord-014597-66vd2mdu 1912 6 recovered recover VBD cord-014597-66vd2mdu 1912 7 first first RB cord-014597-66vd2mdu 1912 8 , , , cord-014597-66vd2mdu 1912 9 due due IN cord-014597-66vd2mdu 1912 10 to to IN cord-014597-66vd2mdu 1912 11 the the DT cord-014597-66vd2mdu 1912 12 presence presence NN cord-014597-66vd2mdu 1912 13 of of IN cord-014597-66vd2mdu 1912 14 only only RB cord-014597-66vd2mdu 1912 15 1 1 CD cord-014597-66vd2mdu 1912 16 antibiotic antibiotic NN cord-014597-66vd2mdu 1912 17 in in IN cord-014597-66vd2mdu 1912 18 the the DT cord-014597-66vd2mdu 1912 19 medium medium NN cord-014597-66vd2mdu 1912 20 ( ( -LRB- cord-014597-66vd2mdu 1912 21 Fig Fig NNP cord-014597-66vd2mdu 1912 22 . . . cord-014597-66vd2mdu 1912 23 1a 1a CD cord-014597-66vd2mdu 1912 24 ) ) -RRB- cord-014597-66vd2mdu 1912 25 . . . cord-014597-66vd2mdu 1913 1 The the DT cord-014597-66vd2mdu 1913 2 pools pool NNS cord-014597-66vd2mdu 1913 3 transfected transfecte VBN cord-014597-66vd2mdu 1913 4 with with IN cord-014597-66vd2mdu 1913 5 three three CD cord-014597-66vd2mdu 1913 6 2GUN 2gun CD cord-014597-66vd2mdu 1913 7 vectors vector NNS cord-014597-66vd2mdu 1913 8 recovered recover VBN cord-014597-66vd2mdu 1913 9 to to TO cord-014597-66vd2mdu 1913 10 maximum maximum VB cord-014597-66vd2mdu 1913 11 viability viability NN cord-014597-66vd2mdu 1913 12 just just RB cord-014597-66vd2mdu 1913 13 a a DT cord-014597-66vd2mdu 1913 14 few few JJ cord-014597-66vd2mdu 1913 15 days day NNS cord-014597-66vd2mdu 1913 16 after after IN cord-014597-66vd2mdu 1913 17 the the DT cord-014597-66vd2mdu 1913 18 2-vector 2-vector CD cord-014597-66vd2mdu 1913 19 2GUN 2gun CD cord-014597-66vd2mdu 1913 20 pools pool NNS cord-014597-66vd2mdu 1913 21 . . . cord-014597-66vd2mdu 1914 1 Recovery recovery NN cord-014597-66vd2mdu 1914 2 of of IN cord-014597-66vd2mdu 1914 3 the the DT cord-014597-66vd2mdu 1914 4 Reference Reference NNP cord-014597-66vd2mdu 1914 5 pools pool NNS cord-014597-66vd2mdu 1914 6 took take VBD cord-014597-66vd2mdu 1914 7 up up RP cord-014597-66vd2mdu 1914 8 to to IN cord-014597-66vd2mdu 1914 9 a a DT cord-014597-66vd2mdu 1914 10 week week NN cord-014597-66vd2mdu 1914 11 longer long RBR cord-014597-66vd2mdu 1914 12 than than IN cord-014597-66vd2mdu 1914 13 the the DT cord-014597-66vd2mdu 1914 14 2GUN 2gun JJ cord-014597-66vd2mdu 1914 15 pools pool NNS cord-014597-66vd2mdu 1914 16 . . . cord-014597-66vd2mdu 1915 1 Production production NN cord-014597-66vd2mdu 1915 2 of of IN cord-014597-66vd2mdu 1915 3 each each DT cord-014597-66vd2mdu 1915 4 pool pool NN cord-014597-66vd2mdu 1915 5 was be VBD cord-014597-66vd2mdu 1915 6 assessed assess VBN cord-014597-66vd2mdu 1915 7 in in IN cord-014597-66vd2mdu 1915 8 a a DT cord-014597-66vd2mdu 1915 9 batch batch NN cord-014597-66vd2mdu 1915 10 production production NN cord-014597-66vd2mdu 1915 11 run run NN cord-014597-66vd2mdu 1915 12 in in IN cord-014597-66vd2mdu 1915 13 shaker shaker NN cord-014597-66vd2mdu 1915 14 flasks flask NNS cord-014597-66vd2mdu 1915 15 . . . cord-014597-66vd2mdu 1916 1 All all DT cord-014597-66vd2mdu 1916 2 2-vector 2-vector CD cord-014597-66vd2mdu 1916 3 2GUN 2gun CD cord-014597-66vd2mdu 1916 4 pools pool NNS cord-014597-66vd2mdu 1916 5 which which WDT cord-014597-66vd2mdu 1916 6 recovered recover VBD cord-014597-66vd2mdu 1916 7 first first RB cord-014597-66vd2mdu 1916 8 produced produce VBD cord-014597-66vd2mdu 1916 9 titers titer NNS cord-014597-66vd2mdu 1916 10 around around IN cord-014597-66vd2mdu 1916 11 0.1 0.1 CD cord-014597-66vd2mdu 1916 12 g g NN cord-014597-66vd2mdu 1916 13 / / SYM cord-014597-66vd2mdu 1916 14 L L NNP cord-014597-66vd2mdu 1916 15 , , , cord-014597-66vd2mdu 1916 16 which which WDT cord-014597-66vd2mdu 1916 17 is be VBZ cord-014597-66vd2mdu 1916 18 almost almost RB cord-014597-66vd2mdu 1916 19 10-fold 10-fold JJ cord-014597-66vd2mdu 1916 20 higher high JJR cord-014597-66vd2mdu 1916 21 as as IN cord-014597-66vd2mdu 1916 22 compared compare VBN cord-014597-66vd2mdu 1916 23 to to IN cord-014597-66vd2mdu 1916 24 the the DT cord-014597-66vd2mdu 1916 25 production production NN cord-014597-66vd2mdu 1916 26 by by IN cord-014597-66vd2mdu 1916 27 Reference reference NN cord-014597-66vd2mdu 1916 28 pools pool NNS cord-014597-66vd2mdu 1916 29 ( ( -LRB- cord-014597-66vd2mdu 1916 30 Fig fig NN cord-014597-66vd2mdu 1916 31 . . . cord-014597-66vd2mdu 1916 32 1b 1b CD cord-014597-66vd2mdu 1916 33 ) ) -RRB- cord-014597-66vd2mdu 1916 34 . . . cord-014597-66vd2mdu 1917 1 The the DT cord-014597-66vd2mdu 1917 2 highest high JJS cord-014597-66vd2mdu 1917 3 titers titer NNS cord-014597-66vd2mdu 1917 4 of of IN cord-014597-66vd2mdu 1917 5 0.5 0.5 CD cord-014597-66vd2mdu 1917 6 g g NN cord-014597-66vd2mdu 1917 7 / / SYM cord-014597-66vd2mdu 1917 8 L L NNP cord-014597-66vd2mdu 1917 9 were be VBD cord-014597-66vd2mdu 1917 10 obtained obtain VBN cord-014597-66vd2mdu 1917 11 in in IN cord-014597-66vd2mdu 1917 12 the the DT cord-014597-66vd2mdu 1917 13 3-vector 3-vector CD cord-014597-66vd2mdu 1917 14 2GUN 2gun CD cord-014597-66vd2mdu 1917 15 pools pool NNS cord-014597-66vd2mdu 1917 16 . . . cord-014597-66vd2mdu 1918 1 These these DT cord-014597-66vd2mdu 1918 2 data datum NNS cord-014597-66vd2mdu 1918 3 show show VBP cord-014597-66vd2mdu 1918 4 that that IN cord-014597-66vd2mdu 1918 5 the the DT cord-014597-66vd2mdu 1918 6 2 2 CD cord-014597-66vd2mdu 1918 7 G G NNP cord-014597-66vd2mdu 1918 8 UNic UNic NNP cord-014597-66vd2mdu 1918 9 ™ ™ VBD cord-014597-66vd2mdu 1918 10 genetic genetic JJ cord-014597-66vd2mdu 1918 11 elements element NNS cord-014597-66vd2mdu 1918 12 can can MD cord-014597-66vd2mdu 1918 13 be be VB cord-014597-66vd2mdu 1918 14 successfully successfully RB cord-014597-66vd2mdu 1918 15 used use VBN cord-014597-66vd2mdu 1918 16 to to TO cord-014597-66vd2mdu 1918 17 obtain obtain VB cord-014597-66vd2mdu 1918 18 a a DT cord-014597-66vd2mdu 1918 19 significant significant JJ cord-014597-66vd2mdu 1918 20 increase increase NN cord-014597-66vd2mdu 1918 21 in in IN cord-014597-66vd2mdu 1918 22 the the DT cord-014597-66vd2mdu 1918 23 titer titer NN cord-014597-66vd2mdu 1918 24 of of IN cord-014597-66vd2mdu 1918 25 difficult difficult JJ cord-014597-66vd2mdu 1918 26 - - HYPH cord-014597-66vd2mdu 1918 27 to to TO cord-014597-66vd2mdu 1918 28 - - HYPH cord-014597-66vd2mdu 1918 29 express express NN cord-014597-66vd2mdu 1918 30 proteins protein NNS cord-014597-66vd2mdu 1918 31 . . . cord-014597-66vd2mdu 1919 1 Similar similar JJ cord-014597-66vd2mdu 1919 2 results result NNS cord-014597-66vd2mdu 1919 3 have have VBP cord-014597-66vd2mdu 1919 4 been be VBN cord-014597-66vd2mdu 1919 5 obtained obtain VBN cord-014597-66vd2mdu 1919 6 with with IN cord-014597-66vd2mdu 1919 7 other other JJ cord-014597-66vd2mdu 1919 8 DTE DTE NNP cord-014597-66vd2mdu 1919 9 proteins protein NNS cord-014597-66vd2mdu 1919 10 , , , cord-014597-66vd2mdu 1919 11 including include VBG cord-014597-66vd2mdu 1919 12 fc fc NN cord-014597-66vd2mdu 1919 13 - - HYPH cord-014597-66vd2mdu 1919 14 fusion fusion NN cord-014597-66vd2mdu 1919 15 proteins protein NNS cord-014597-66vd2mdu 1919 16 and and CC cord-014597-66vd2mdu 1919 17 bi bi JJ cord-014597-66vd2mdu 1919 18 - - JJ cord-014597-66vd2mdu 1919 19 specific specific JJ cord-014597-66vd2mdu 1919 20 antibodies antibody NNS cord-014597-66vd2mdu 1919 21 ( ( -LRB- cord-014597-66vd2mdu 1919 22 not not RB cord-014597-66vd2mdu 1919 23 shown show VBN cord-014597-66vd2mdu 1919 24 ) ) -RRB- cord-014597-66vd2mdu 1919 25 . . . cord-014597-66vd2mdu 1920 1 The the DT cord-014597-66vd2mdu 1920 2 expression expression NN cord-014597-66vd2mdu 1920 3 of of IN cord-014597-66vd2mdu 1920 4 a a DT cord-014597-66vd2mdu 1920 5 large large JJ cord-014597-66vd2mdu 1920 6 , , , cord-014597-66vd2mdu 1920 7 glycosylated glycosylated JJ cord-014597-66vd2mdu 1920 8 multimeric multimeric NN cord-014597-66vd2mdu 1920 9 difficult difficult JJ cord-014597-66vd2mdu 1920 10 to to TO cord-014597-66vd2mdu 1920 11 express express VB cord-014597-66vd2mdu 1920 12 protein protein NN cord-014597-66vd2mdu 1920 13 can can MD cord-014597-66vd2mdu 1920 14 be be VB cord-014597-66vd2mdu 1920 15 increased increase VBN cord-014597-66vd2mdu 1920 16 more more JJR cord-014597-66vd2mdu 1920 17 than than IN cord-014597-66vd2mdu 1920 18 ten ten CD cord-014597-66vd2mdu 1920 19 - - HYPH cord-014597-66vd2mdu 1920 20 fold fold NN cord-014597-66vd2mdu 1920 21 in in IN cord-014597-66vd2mdu 1920 22 CHO CHO NNP cord-014597-66vd2mdu 1920 23 GS GS NNP cord-014597-66vd2mdu 1920 24 pools pool NNS cord-014597-66vd2mdu 1920 25 by by IN cord-014597-66vd2mdu 1920 26 application application NN cord-014597-66vd2mdu 1920 27 of of IN cord-014597-66vd2mdu 1920 28 2 2 CD cord-014597-66vd2mdu 1920 29 G G NNP cord-014597-66vd2mdu 1920 30 UNic UNic NNP cord-014597-66vd2mdu 1920 31 ™ ™ VBD cord-014597-66vd2mdu 1920 32 genetic genetic JJ cord-014597-66vd2mdu 1920 33 elements element NNS cord-014597-66vd2mdu 1920 34 . . . cord-014597-66vd2mdu 1921 1 The the DT cord-014597-66vd2mdu 1921 2 highest high JJS cord-014597-66vd2mdu 1921 3 expression expression NN cord-014597-66vd2mdu 1921 4 of of IN cord-014597-66vd2mdu 1921 5 is be VBZ cord-014597-66vd2mdu 1921 6 obtained obtain VBN cord-014597-66vd2mdu 1921 7 using use VBG cord-014597-66vd2mdu 1921 8 a a DT cord-014597-66vd2mdu 1921 9 separate separate JJ cord-014597-66vd2mdu 1921 10 vector vector NN cord-014597-66vd2mdu 1921 11 for for IN cord-014597-66vd2mdu 1921 12 each each DT cord-014597-66vd2mdu 1921 13 subunit subunit NN cord-014597-66vd2mdu 1921 14 . . . cord-014597-66vd2mdu 1922 1 Characterization characterization NN cord-014597-66vd2mdu 1922 2 of of IN cord-014597-66vd2mdu 1922 3 antibody antibody NN cord-014597-66vd2mdu 1922 4 - - HYPH cord-014597-66vd2mdu 1922 5 producing produce VBG cord-014597-66vd2mdu 1922 6 CHO CHO NNP cord-014597-66vd2mdu 1922 7 cells cell NNS cord-014597-66vd2mdu 1922 8 with with IN cord-014597-66vd2mdu 1922 9 chromosome chromosome NN cord-014597-66vd2mdu 1922 10 aneuploidy aneuploidy NN cord-014597-66vd2mdu 1923 1 Noriko Noriko NNP cord-014597-66vd2mdu 1923 2 Yamano Yamano NNP cord-014597-66vd2mdu 1923 3 1,2 1,2 CD cord-014597-66vd2mdu 1923 4 , , , cord-014597-66vd2mdu 1923 5 Sho Sho NNP cord-014597-66vd2mdu 1923 6 Tanaka Tanaka NNP cord-014597-66vd2mdu 1923 7 Background Background NNP cord-014597-66vd2mdu 1923 8 Chinese chinese JJ cord-014597-66vd2mdu 1923 9 hamster hamster NN cord-014597-66vd2mdu 1923 10 ovary ovary NN cord-014597-66vd2mdu 1923 11 ( ( -LRB- cord-014597-66vd2mdu 1923 12 CHO CHO NNP cord-014597-66vd2mdu 1923 13 ) ) -RRB- cord-014597-66vd2mdu 1923 14 cells cell NNS cord-014597-66vd2mdu 1923 15 are be VBP cord-014597-66vd2mdu 1923 16 commonly commonly RB cord-014597-66vd2mdu 1923 17 used use VBN cord-014597-66vd2mdu 1923 18 as as IN cord-014597-66vd2mdu 1923 19 host host NN cord-014597-66vd2mdu 1923 20 cells cell NNS cord-014597-66vd2mdu 1923 21 to to TO cord-014597-66vd2mdu 1923 22 produce produce VB cord-014597-66vd2mdu 1923 23 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 1923 24 . . . cord-014597-66vd2mdu 1924 1 However however RB cord-014597-66vd2mdu 1924 2 , , , cord-014597-66vd2mdu 1924 3 the the DT cord-014597-66vd2mdu 1924 4 number number NN cord-014597-66vd2mdu 1924 5 of of IN cord-014597-66vd2mdu 1924 6 chromosomes chromosome NNS cord-014597-66vd2mdu 1924 7 in in IN cord-014597-66vd2mdu 1924 8 CHO CHO NNP cord-014597-66vd2mdu 1924 9 cells cell NNS cord-014597-66vd2mdu 1924 10 varies vary VBZ cord-014597-66vd2mdu 1924 11 . . . cord-014597-66vd2mdu 1925 1 Previously previously RB cord-014597-66vd2mdu 1925 2 , , , cord-014597-66vd2mdu 1925 3 DG44-SC20 DG44-SC20 NNP cord-014597-66vd2mdu 1925 4 and and CC cord-014597-66vd2mdu 1925 5 DG44-SC39 dg44-sc39 JJ cord-014597-66vd2mdu 1925 6 cell cell NN cord-014597-66vd2mdu 1925 7 lines line NNS cord-014597-66vd2mdu 1925 8 with with IN cord-014597-66vd2mdu 1925 9 modal modal JJ cord-014597-66vd2mdu 1925 10 chromosome chromosome NN cord-014597-66vd2mdu 1925 11 numbers number NNS cord-014597-66vd2mdu 1925 12 of of IN cord-014597-66vd2mdu 1925 13 20 20 CD cord-014597-66vd2mdu 1925 14 and and CC cord-014597-66vd2mdu 1925 15 39 39 CD cord-014597-66vd2mdu 1925 16 were be VBD cord-014597-66vd2mdu 1925 17 isolated isolate VBN cord-014597-66vd2mdu 1925 18 from from IN cord-014597-66vd2mdu 1925 19 parental parental JJ cord-014597-66vd2mdu 1925 20 CHO CHO NNP cord-014597-66vd2mdu 1925 21 - - HYPH cord-014597-66vd2mdu 1925 22 DG44 DG44 NNP cord-014597-66vd2mdu 1925 23 cells cell NNS cord-014597-66vd2mdu 1925 24 , , , cord-014597-66vd2mdu 1925 25 from from IN cord-014597-66vd2mdu 1925 26 which which WDT cord-014597-66vd2mdu 1925 27 IgG3-expressing igg3-expresse VBG cord-014597-66vd2mdu 1925 28 cell cell NN cord-014597-66vd2mdu 1925 29 lines line NNS cord-014597-66vd2mdu 1925 30 named name VBN cord-014597-66vd2mdu 1925 31 IgG3-SC20 IgG3-SC20 NNP cord-014597-66vd2mdu 1925 32 and and CC cord-014597-66vd2mdu 1925 33 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1925 34 were be VBD cord-014597-66vd2mdu 1925 35 established establish VBN cord-014597-66vd2mdu 1925 36 , , , cord-014597-66vd2mdu 1925 37 respectively respectively RB cord-014597-66vd2mdu 1925 38 . . . cord-014597-66vd2mdu 1926 1 The the DT cord-014597-66vd2mdu 1926 2 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1926 3 cell cell NN cord-014597-66vd2mdu 1926 4 pool pool NN cord-014597-66vd2mdu 1926 5 showed show VBD cord-014597-66vd2mdu 1926 6 a a DT cord-014597-66vd2mdu 1926 7 higher higher RBR cord-014597-66vd2mdu 1926 8 specific specific JJ cord-014597-66vd2mdu 1926 9 IgG3 igg3 NN cord-014597-66vd2mdu 1926 10 production production NN cord-014597-66vd2mdu 1926 11 rate rate NN cord-014597-66vd2mdu 1926 12 than than IN cord-014597-66vd2mdu 1926 13 the the DT cord-014597-66vd2mdu 1926 14 IgG3-SC20 IgG3-SC20 `` cord-014597-66vd2mdu 1926 15 cell cell NN cord-014597-66vd2mdu 1926 16 pool pool NN cord-014597-66vd2mdu 1926 17 [ [ -LRB- cord-014597-66vd2mdu 1926 18 1 1 CD cord-014597-66vd2mdu 1926 19 ] ] -RRB- cord-014597-66vd2mdu 1926 20 . . . cord-014597-66vd2mdu 1927 1 Even even RB cord-014597-66vd2mdu 1927 2 though though IN cord-014597-66vd2mdu 1927 3 all all DT cord-014597-66vd2mdu 1927 4 of of IN cord-014597-66vd2mdu 1927 5 the the DT cord-014597-66vd2mdu 1927 6 IgG3-SC20 IgG3-SC20 NNP cord-014597-66vd2mdu 1927 7 clones clone NNS cord-014597-66vd2mdu 1927 8 and and CC cord-014597-66vd2mdu 1927 9 half half NN cord-014597-66vd2mdu 1927 10 of of IN cord-014597-66vd2mdu 1927 11 the the DT cord-014597-66vd2mdu 1927 12 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1927 13 clones clone NNS cord-014597-66vd2mdu 1927 14 contained contain VBD cord-014597-66vd2mdu 1927 15 the the DT cord-014597-66vd2mdu 1927 16 same same JJ cord-014597-66vd2mdu 1927 17 number number NN cord-014597-66vd2mdu 1927 18 of of IN cord-014597-66vd2mdu 1927 19 vector vector NN cord-014597-66vd2mdu 1927 20 integration integration NN cord-014597-66vd2mdu 1927 21 sites site NNS cord-014597-66vd2mdu 1927 22 ( ( -LRB- cord-014597-66vd2mdu 1927 23 single single JJ cord-014597-66vd2mdu 1927 24 integration integration NN cord-014597-66vd2mdu 1927 25 site site NN cord-014597-66vd2mdu 1927 26 ) ) -RRB- cord-014597-66vd2mdu 1927 27 , , , cord-014597-66vd2mdu 1927 28 IgG igg NN cord-014597-66vd2mdu 1927 29 - - HYPH cord-014597-66vd2mdu 1927 30 SC39 SC39 NNP cord-014597-66vd2mdu 1927 31 cell cell NN cord-014597-66vd2mdu 1927 32 clones clone NNS cord-014597-66vd2mdu 1927 33 produced produce VBD cord-014597-66vd2mdu 1927 34 more more JJR cord-014597-66vd2mdu 1927 35 IgG3 igg3 NN cord-014597-66vd2mdu 1927 36 following follow VBG cord-014597-66vd2mdu 1927 37 the the DT cord-014597-66vd2mdu 1927 38 culture culture NN cord-014597-66vd2mdu 1927 39 of of IN cord-014597-66vd2mdu 1927 40 single single JJ cord-014597-66vd2mdu 1927 41 - - HYPH cord-014597-66vd2mdu 1927 42 cell cell NN cord-014597-66vd2mdu 1927 43 clones clone NNS cord-014597-66vd2mdu 1927 44 than than IN cord-014597-66vd2mdu 1927 45 any any DT cord-014597-66vd2mdu 1927 46 of of IN cord-014597-66vd2mdu 1927 47 the the DT cord-014597-66vd2mdu 1927 48 IgG3-SC20 IgG3-SC20 NNP cord-014597-66vd2mdu 1927 49 clones clone NNS cord-014597-66vd2mdu 1927 50 [ [ -LRB- cord-014597-66vd2mdu 1927 51 1 1 CD cord-014597-66vd2mdu 1927 52 ] ] -RRB- cord-014597-66vd2mdu 1927 53 . . . cord-014597-66vd2mdu 1928 1 In in IN cord-014597-66vd2mdu 1928 2 this this DT cord-014597-66vd2mdu 1928 3 study study NN cord-014597-66vd2mdu 1928 4 , , , cord-014597-66vd2mdu 1928 5 we -PRON- PRP cord-014597-66vd2mdu 1928 6 performed perform VBD cord-014597-66vd2mdu 1928 7 transcriptome transcriptome NN cord-014597-66vd2mdu 1928 8 analysis analysis NN cord-014597-66vd2mdu 1928 9 to to TO cord-014597-66vd2mdu 1928 10 investigate investigate VB cord-014597-66vd2mdu 1928 11 the the DT cord-014597-66vd2mdu 1928 12 characteristics characteristic NNS cord-014597-66vd2mdu 1928 13 of of IN cord-014597-66vd2mdu 1928 14 high high JJ cord-014597-66vd2mdu 1928 15 - - HYPH cord-014597-66vd2mdu 1928 16 producer producer NN cord-014597-66vd2mdu 1928 17 cells cell NNS cord-014597-66vd2mdu 1928 18 with with IN cord-014597-66vd2mdu 1928 19 chromosome chromosome NN cord-014597-66vd2mdu 1928 20 aneuploidy aneuploidy NN cord-014597-66vd2mdu 1928 21 . . . cord-014597-66vd2mdu 1929 1 Transcriptome Transcriptome NNP cord-014597-66vd2mdu 1929 2 analyses analysis NNS cord-014597-66vd2mdu 1929 3 using use VBG cord-014597-66vd2mdu 1929 4 amplified amplify VBN cord-014597-66vd2mdu 1929 5 fragment fragment NN cord-014597-66vd2mdu 1929 6 length length NN cord-014597-66vd2mdu 1929 7 polymorphism polymorphism NN cord-014597-66vd2mdu 1929 8 ( ( -LRB- cord-014597-66vd2mdu 1929 9 AFLP)-based aflp)-based JJ cord-014597-66vd2mdu 1929 10 high high JJ cord-014597-66vd2mdu 1929 11 - - HYPH cord-014597-66vd2mdu 1929 12 coverage coverage NN cord-014597-66vd2mdu 1929 13 expression expression NN cord-014597-66vd2mdu 1929 14 profiling profiling NN cord-014597-66vd2mdu 1929 15 ( ( -LRB- cord-014597-66vd2mdu 1929 16 HiCEP HiCEP NNP cord-014597-66vd2mdu 1929 17 ) ) -RRB- cord-014597-66vd2mdu 1929 18 and and CC cord-014597-66vd2mdu 1930 1 de de NNP cord-014597-66vd2mdu 1930 2 novo novo NNP cord-014597-66vd2mdu 1930 3 mRNA mRNA NNP cord-014597-66vd2mdu 1930 4 - - HYPH cord-014597-66vd2mdu 1930 5 seq seq NNP cord-014597-66vd2mdu 1930 6 were be VBD cord-014597-66vd2mdu 1930 7 performed perform VBN cord-014597-66vd2mdu 1930 8 on on IN cord-014597-66vd2mdu 1930 9 DG44-SC20 DG44-SC20 NNP cord-014597-66vd2mdu 1930 10 , , , cord-014597-66vd2mdu 1930 11 DG44-SC39 DG44-SC39 NNP cord-014597-66vd2mdu 1930 12 , , , cord-014597-66vd2mdu 1930 13 IgG3-SC20 IgG3-SC20 '' cord-014597-66vd2mdu 1930 14 and and CC cord-014597-66vd2mdu 1930 15 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1930 16 . . . cord-014597-66vd2mdu 1931 1 To to TO cord-014597-66vd2mdu 1931 2 compare compare VB cord-014597-66vd2mdu 1931 3 cell cell NN cord-014597-66vd2mdu 1931 4 lines line NNS cord-014597-66vd2mdu 1931 5 with with IN cord-014597-66vd2mdu 1931 6 different different JJ cord-014597-66vd2mdu 1931 7 numbers number NNS cord-014597-66vd2mdu 1931 8 of of IN cord-014597-66vd2mdu 1931 9 chromosomes chromosome NNS cord-014597-66vd2mdu 1931 10 , , , cord-014597-66vd2mdu 1931 11 transcriptome transcriptome NN cord-014597-66vd2mdu 1931 12 data datum NNS cord-014597-66vd2mdu 1931 13 from from IN cord-014597-66vd2mdu 1931 14 mRNA mRNA NNP cord-014597-66vd2mdu 1931 15 - - HYPH cord-014597-66vd2mdu 1931 16 seq seq NNP cord-014597-66vd2mdu 1931 17 were be VBD cord-014597-66vd2mdu 1931 18 adjusted adjust VBN cord-014597-66vd2mdu 1931 19 for for IN cord-014597-66vd2mdu 1931 20 cell cell NN cord-014597-66vd2mdu 1931 21 number number NN cord-014597-66vd2mdu 1931 22 using use VBG cord-014597-66vd2mdu 1931 23 RNA RNA NNP cord-014597-66vd2mdu 1931 24 reference reference NN cord-014597-66vd2mdu 1931 25 materials material NNS cord-014597-66vd2mdu 1931 26 ( ( -LRB- cord-014597-66vd2mdu 1931 27 NMIJ NMIJ NNP cord-014597-66vd2mdu 1931 28 CRM CRM NNP cord-014597-66vd2mdu 1931 29 6204-a 6204-a CD cord-014597-66vd2mdu 1931 30 ; ; : cord-014597-66vd2mdu 1931 31 National National NNP cord-014597-66vd2mdu 1931 32 Institute Institute NNP cord-014597-66vd2mdu 1931 33 of of IN cord-014597-66vd2mdu 1931 34 Advanced Advanced NNP cord-014597-66vd2mdu 1931 35 Industrial Industrial NNP cord-014597-66vd2mdu 1931 36 Science Science NNP cord-014597-66vd2mdu 1931 37 and and CC cord-014597-66vd2mdu 1931 38 Technology Technology NNP cord-014597-66vd2mdu 1931 39 ) ) -RRB- cord-014597-66vd2mdu 1931 40 mixed mix VBN cord-014597-66vd2mdu 1931 41 at at IN cord-014597-66vd2mdu 1931 42 equal equal JJ cord-014597-66vd2mdu 1931 43 amounts amount NNS cord-014597-66vd2mdu 1931 44 per per IN cord-014597-66vd2mdu 1931 45 cell cell NN cord-014597-66vd2mdu 1931 46 . . . cord-014597-66vd2mdu 1932 1 Pathways pathway NNS cord-014597-66vd2mdu 1932 2 related relate VBN cord-014597-66vd2mdu 1932 3 to to IN cord-014597-66vd2mdu 1932 4 differentially differentially RB cord-014597-66vd2mdu 1932 5 expressed express VBN cord-014597-66vd2mdu 1932 6 genes gene NNS cord-014597-66vd2mdu 1932 7 were be VBD cord-014597-66vd2mdu 1932 8 searched search VBN cord-014597-66vd2mdu 1932 9 using use VBG cord-014597-66vd2mdu 1932 10 KeyMolnet KeyMolnet NNP cord-014597-66vd2mdu 1932 11 ( ( -LRB- cord-014597-66vd2mdu 1932 12 KM KM NNP cord-014597-66vd2mdu 1932 13 Data Data NNP cord-014597-66vd2mdu 1932 14 ) ) -RRB- cord-014597-66vd2mdu 1932 15 . . . cord-014597-66vd2mdu 1933 1 High high JJ cord-014597-66vd2mdu 1933 2 - - HYPH cord-014597-66vd2mdu 1933 3 chromosome chromosome NN cord-014597-66vd2mdu 1933 4 - - HYPH cord-014597-66vd2mdu 1933 5 number number NN cord-014597-66vd2mdu 1933 6 CHO CHO NNP cord-014597-66vd2mdu 1933 7 cells cell NNS cord-014597-66vd2mdu 1933 8 showed show VBD cord-014597-66vd2mdu 1933 9 larger large JJR cord-014597-66vd2mdu 1933 10 cell cell NN cord-014597-66vd2mdu 1933 11 diameters diameter NNS cord-014597-66vd2mdu 1933 12 , , , cord-014597-66vd2mdu 1933 13 as as IN cord-014597-66vd2mdu 1933 14 determined determine VBN cord-014597-66vd2mdu 1933 15 by by IN cord-014597-66vd2mdu 1933 16 Vi Vi NNP cord-014597-66vd2mdu 1933 17 - - HYPH cord-014597-66vd2mdu 1933 18 cell cell NN cord-014597-66vd2mdu 1933 19 ( ( -LRB- cord-014597-66vd2mdu 1933 20 Beckman Beckman NNP cord-014597-66vd2mdu 1933 21 Coulter Coulter NNP cord-014597-66vd2mdu 1933 22 ) ) -RRB- cord-014597-66vd2mdu 1933 23 measurement measurement NN cord-014597-66vd2mdu 1933 24 . . . cord-014597-66vd2mdu 1934 1 The the DT cord-014597-66vd2mdu 1934 2 predicted predict VBN cord-014597-66vd2mdu 1934 3 volume volume NN cord-014597-66vd2mdu 1934 4 ratios ratio NNS cord-014597-66vd2mdu 1934 5 , , , cord-014597-66vd2mdu 1934 6 based base VBN cord-014597-66vd2mdu 1934 7 on on IN cord-014597-66vd2mdu 1934 8 these these DT cord-014597-66vd2mdu 1934 9 diameters diameter NNS cord-014597-66vd2mdu 1934 10 , , , cord-014597-66vd2mdu 1934 11 are be VBP cord-014597-66vd2mdu 1934 12 2.24 2.24 CD cord-014597-66vd2mdu 1935 1 ( ( -LRB- cord-014597-66vd2mdu 1935 2 DG44-SC39 DG44-SC39 NNP cord-014597-66vd2mdu 1935 3 : : : cord-014597-66vd2mdu 1935 4 DG44-SC20 DG44-SC20 NNP cord-014597-66vd2mdu 1935 5 ) ) -RRB- cord-014597-66vd2mdu 1935 6 and and CC cord-014597-66vd2mdu 1935 7 1.59 1.59 CD cord-014597-66vd2mdu 1935 8 ( ( -LRB- cord-014597-66vd2mdu 1935 9 IgG3-SC39 igg3-sc39 CD cord-014597-66vd2mdu 1935 10 : : : cord-014597-66vd2mdu 1935 11 IgG3-SC20 IgG3-SC20 '' cord-014597-66vd2mdu 1935 12 ) ) -RRB- cord-014597-66vd2mdu 1935 13 . . . cord-014597-66vd2mdu 1936 1 The the DT cord-014597-66vd2mdu 1936 2 levels level NNS cord-014597-66vd2mdu 1936 3 of of IN cord-014597-66vd2mdu 1936 4 β β NN cord-014597-66vd2mdu 1936 5 - - HYPH cord-014597-66vd2mdu 1936 6 actin actin NN cord-014597-66vd2mdu 1936 7 and and CC cord-014597-66vd2mdu 1936 8 the the DT cord-014597-66vd2mdu 1936 9 products product NNS cord-014597-66vd2mdu 1936 10 of of IN cord-014597-66vd2mdu 1936 11 most most JJS cord-014597-66vd2mdu 1936 12 other other JJ cord-014597-66vd2mdu 1936 13 genes gene NNS cord-014597-66vd2mdu 1936 14 that that WDT cord-014597-66vd2mdu 1936 15 were be VBD cord-014597-66vd2mdu 1936 16 detected detect VBN cord-014597-66vd2mdu 1936 17 by by IN cord-014597-66vd2mdu 1936 18 mRNA mRNA NNP cord-014597-66vd2mdu 1936 19 - - HYPH cord-014597-66vd2mdu 1936 20 seq seq NNP cord-014597-66vd2mdu 1936 21 differed differ VBD cord-014597-66vd2mdu 1936 22 by by IN cord-014597-66vd2mdu 1936 23 approximately approximately RB cord-014597-66vd2mdu 1936 24 20 20 CD cord-014597-66vd2mdu 1936 25 % % NN cord-014597-66vd2mdu 1936 26 in in IN cord-014597-66vd2mdu 1936 27 the the DT cord-014597-66vd2mdu 1936 28 comparison comparison NN cord-014597-66vd2mdu 1936 29 between between IN cord-014597-66vd2mdu 1936 30 SC39 SC39 NNP cord-014597-66vd2mdu 1936 31 and and CC cord-014597-66vd2mdu 1936 32 SC20 SC20 NNP cord-014597-66vd2mdu 1937 1 ( ( -LRB- cord-014597-66vd2mdu 1937 2 SC39 SC39 NNP cord-014597-66vd2mdu 1937 3 > > XX cord-014597-66vd2mdu 1937 4 SC20 SC20 NNP cord-014597-66vd2mdu 1937 5 ) ) -RRB- cord-014597-66vd2mdu 1937 6 . . . cord-014597-66vd2mdu 1938 1 Based base VBN cord-014597-66vd2mdu 1938 2 on on IN cord-014597-66vd2mdu 1938 3 the the DT cord-014597-66vd2mdu 1938 4 analysis analysis NN cord-014597-66vd2mdu 1938 5 of of IN cord-014597-66vd2mdu 1938 6 gene gene NN cord-014597-66vd2mdu 1938 7 expression expression NN cord-014597-66vd2mdu 1938 8 levels level NNS cord-014597-66vd2mdu 1938 9 per per IN cord-014597-66vd2mdu 1938 10 cell cell NN cord-014597-66vd2mdu 1938 11 volume volume NN cord-014597-66vd2mdu 1938 12 , , , cord-014597-66vd2mdu 1938 13 approximately approximately RB cord-014597-66vd2mdu 1938 14 90 90 CD cord-014597-66vd2mdu 1938 15 % % NN cord-014597-66vd2mdu 1938 16 of of IN cord-014597-66vd2mdu 1938 17 detected detect VBN cord-014597-66vd2mdu 1938 18 genes gene NNS cord-014597-66vd2mdu 1938 19 showed show VBD cord-014597-66vd2mdu 1938 20 lower low JJR cord-014597-66vd2mdu 1938 21 expression expression NN cord-014597-66vd2mdu 1938 22 in in IN cord-014597-66vd2mdu 1938 23 both both DT cord-014597-66vd2mdu 1938 24 DG44-SC39 dg44-sc39 NN cord-014597-66vd2mdu 1938 25 and and CC cord-014597-66vd2mdu 1938 26 IgG3-SC39 igg3-sc39 CD cord-014597-66vd2mdu 1938 27 compared compare VBN cord-014597-66vd2mdu 1938 28 with with IN cord-014597-66vd2mdu 1938 29 the the DT cord-014597-66vd2mdu 1938 30 levels level NNS cord-014597-66vd2mdu 1938 31 in in IN cord-014597-66vd2mdu 1938 32 DG44-SC20 DG44-SC20 NNP cord-014597-66vd2mdu 1938 33 and and CC cord-014597-66vd2mdu 1938 34 IgG3-SC20 IgG3-SC20 NNP cord-014597-66vd2mdu 1938 35 , , , cord-014597-66vd2mdu 1938 36 respectively respectively RB cord-014597-66vd2mdu 1938 37 . . . cord-014597-66vd2mdu 1939 1 In in IN cord-014597-66vd2mdu 1939 2 addition addition NN cord-014597-66vd2mdu 1939 3 , , , cord-014597-66vd2mdu 1939 4 the the DT cord-014597-66vd2mdu 1939 5 number number NN cord-014597-66vd2mdu 1939 6 of of IN cord-014597-66vd2mdu 1939 7 genes gene NNS cord-014597-66vd2mdu 1939 8 whose whose WP$ cord-014597-66vd2mdu 1939 9 expression expression NN cord-014597-66vd2mdu 1939 10 level level NN cord-014597-66vd2mdu 1939 11 was be VBD cord-014597-66vd2mdu 1939 12 decreased decrease VBN cord-014597-66vd2mdu 1939 13 in in IN cord-014597-66vd2mdu 1939 14 IgG3-SC39 igg3-sc39 CD cord-014597-66vd2mdu 1939 15 compared compare VBN cord-014597-66vd2mdu 1939 16 with with IN cord-014597-66vd2mdu 1939 17 that that DT cord-014597-66vd2mdu 1939 18 in in IN cord-014597-66vd2mdu 1939 19 DG44-SC39 dg44-sc39 NN cord-014597-66vd2mdu 1939 20 was be VBD cord-014597-66vd2mdu 1939 21 larger large JJR cord-014597-66vd2mdu 1939 22 than than IN cord-014597-66vd2mdu 1939 23 those those DT cord-014597-66vd2mdu 1939 24 showing show VBG cord-014597-66vd2mdu 1939 25 the the DT cord-014597-66vd2mdu 1939 26 opposite opposite JJ cord-014597-66vd2mdu 1939 27 pattern pattern NN cord-014597-66vd2mdu 1939 28 . . . cord-014597-66vd2mdu 1940 1 The the DT cord-014597-66vd2mdu 1940 2 results result NNS cord-014597-66vd2mdu 1940 3 of of IN cord-014597-66vd2mdu 1940 4 the the DT cord-014597-66vd2mdu 1940 5 comparisons comparison NNS cord-014597-66vd2mdu 1940 6 between between IN cord-014597-66vd2mdu 1940 7 IgG3-SC20 igg3-sc20 $ cord-014597-66vd2mdu 1940 8 and and CC cord-014597-66vd2mdu 1940 9 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1940 10 indicate indicate VBP cord-014597-66vd2mdu 1940 11 that that IN cord-014597-66vd2mdu 1940 12 differentially differentially RB cord-014597-66vd2mdu 1940 13 expressed express VBN cord-014597-66vd2mdu 1940 14 genes gene NNS cord-014597-66vd2mdu 1940 15 were be VBD cord-014597-66vd2mdu 1940 16 mainly mainly RB cord-014597-66vd2mdu 1940 17 related relate VBN cord-014597-66vd2mdu 1940 18 to to IN cord-014597-66vd2mdu 1940 19 cell cell NN cord-014597-66vd2mdu 1940 20 growth growth NN cord-014597-66vd2mdu 1940 21 ( ( -LRB- cord-014597-66vd2mdu 1940 22 e.g. e.g. RB cord-014597-66vd2mdu 1940 23 Myc Myc NNP cord-014597-66vd2mdu 1940 24 , , , cord-014597-66vd2mdu 1940 25 SMAD SMAD NNP cord-014597-66vd2mdu 1940 26 ) ) -RRB- cord-014597-66vd2mdu 1940 27 , , , cord-014597-66vd2mdu 1940 28 apoptosis apoptosis NN cord-014597-66vd2mdu 1940 29 ( ( -LRB- cord-014597-66vd2mdu 1940 30 e.g. e.g. DT cord-014597-66vd2mdu 1940 31 Caspase Caspase NNP cord-014597-66vd2mdu 1940 32 ) ) -RRB- cord-014597-66vd2mdu 1940 33 , , , cord-014597-66vd2mdu 1940 34 lipid lipid NN cord-014597-66vd2mdu 1940 35 metabolism metabolism NN cord-014597-66vd2mdu 1940 36 ( ( -LRB- cord-014597-66vd2mdu 1940 37 e.g. e.g. RB cord-014597-66vd2mdu 1940 38 SREBP SREBP NNP cord-014597-66vd2mdu 1940 39 , , , cord-014597-66vd2mdu 1940 40 PPARγ PPARγ NNS cord-014597-66vd2mdu 1940 41 ) ) -RRB- cord-014597-66vd2mdu 1940 42 and and CC cord-014597-66vd2mdu 1940 43 epigenetic epigenetic JJ cord-014597-66vd2mdu 1940 44 histone histone NN cord-014597-66vd2mdu 1940 45 modification modification NN cord-014597-66vd2mdu 1940 46 ( ( -LRB- cord-014597-66vd2mdu 1940 47 e.g. e.g. RB cord-014597-66vd2mdu 1940 48 BRCA BRCA NNP cord-014597-66vd2mdu 1940 49 , , , cord-014597-66vd2mdu 1940 50 HAT HAT NNP cord-014597-66vd2mdu 1940 51 ) ) -RRB- cord-014597-66vd2mdu 1940 52 pathways pathway NNS cord-014597-66vd2mdu 1940 53 . . . cord-014597-66vd2mdu 1941 1 The the DT cord-014597-66vd2mdu 1941 2 mRNA mRNA NNP cord-014597-66vd2mdu 1941 3 levels level NNS cord-014597-66vd2mdu 1941 4 of of IN cord-014597-66vd2mdu 1941 5 Myc Myc NNP cord-014597-66vd2mdu 1941 6 , , , cord-014597-66vd2mdu 1941 7 SMAD SMAD NNP cord-014597-66vd2mdu 1941 8 , , , cord-014597-66vd2mdu 1941 9 Caspase Caspase NNP cord-014597-66vd2mdu 1941 10 , , , cord-014597-66vd2mdu 1941 11 BRCA BRCA NNP cord-014597-66vd2mdu 1941 12 and and CC cord-014597-66vd2mdu 1941 13 HAT HAT NNP cord-014597-66vd2mdu 1941 14 related relate VBN cord-014597-66vd2mdu 1941 15 genes gene NNS cord-014597-66vd2mdu 1941 16 were be VBD cord-014597-66vd2mdu 1941 17 lower low JJR cord-014597-66vd2mdu 1941 18 in in IN cord-014597-66vd2mdu 1941 19 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1941 20 , , , cord-014597-66vd2mdu 1941 21 while while IN cord-014597-66vd2mdu 1941 22 those those DT cord-014597-66vd2mdu 1941 23 of of IN cord-014597-66vd2mdu 1941 24 SREBP SREBP NNP cord-014597-66vd2mdu 1941 25 and and CC cord-014597-66vd2mdu 1941 26 PPARγ PPARγ NNS cord-014597-66vd2mdu 1941 27 related related JJ cord-014597-66vd2mdu 1941 28 genes gene NNS cord-014597-66vd2mdu 1941 29 were be VBD cord-014597-66vd2mdu 1941 30 higher high JJR cord-014597-66vd2mdu 1941 31 in in IN cord-014597-66vd2mdu 1941 32 IgG3-SC39 IgG3-SC39 NNP cord-014597-66vd2mdu 1941 33 . . . cord-014597-66vd2mdu 1942 1 The the DT cord-014597-66vd2mdu 1942 2 effects effect NNS cord-014597-66vd2mdu 1942 3 of of IN cord-014597-66vd2mdu 1942 4 these these DT cord-014597-66vd2mdu 1942 5 pathways pathway NNS cord-014597-66vd2mdu 1942 6 on on IN cord-014597-66vd2mdu 1942 7 antibody antibody NN cord-014597-66vd2mdu 1942 8 production production NN cord-014597-66vd2mdu 1942 9 should should MD cord-014597-66vd2mdu 1942 10 be be VB cord-014597-66vd2mdu 1942 11 examined examine VBN cord-014597-66vd2mdu 1942 12 in in IN cord-014597-66vd2mdu 1942 13 future future NN cord-014597-66vd2mdu 1942 14 . . . cord-014597-66vd2mdu 1943 1 In in IN cord-014597-66vd2mdu 1943 2 this this DT cord-014597-66vd2mdu 1943 3 study study NN cord-014597-66vd2mdu 1943 4 , , , cord-014597-66vd2mdu 1943 5 we -PRON- PRP cord-014597-66vd2mdu 1943 6 found find VBD cord-014597-66vd2mdu 1943 7 that that IN cord-014597-66vd2mdu 1943 8 high high JJ cord-014597-66vd2mdu 1943 9 - - HYPH cord-014597-66vd2mdu 1943 10 chromosome chromosome NN cord-014597-66vd2mdu 1943 11 - - HYPH cord-014597-66vd2mdu 1943 12 number number NN cord-014597-66vd2mdu 1943 13 CHO CHO NNP cord-014597-66vd2mdu 1943 14 cells cell NNS cord-014597-66vd2mdu 1943 15 have have VBP cord-014597-66vd2mdu 1943 16 lower low JJR cord-014597-66vd2mdu 1943 17 amounts amount NNS cord-014597-66vd2mdu 1943 18 of of IN cord-014597-66vd2mdu 1943 19 mRNA mrna NN cord-014597-66vd2mdu 1943 20 relative relative JJ cord-014597-66vd2mdu 1943 21 to to IN cord-014597-66vd2mdu 1943 22 their -PRON- PRP$ cord-014597-66vd2mdu 1943 23 volume volume NN cord-014597-66vd2mdu 1943 24 . . . cord-014597-66vd2mdu 1944 1 A a DT cord-014597-66vd2mdu 1944 2 reduction reduction NN cord-014597-66vd2mdu 1944 3 per per IN cord-014597-66vd2mdu 1944 4 unit unit NN cord-014597-66vd2mdu 1944 5 volume volume NN cord-014597-66vd2mdu 1944 6 in in IN cord-014597-66vd2mdu 1944 7 the the DT cord-014597-66vd2mdu 1944 8 expression expression NN cord-014597-66vd2mdu 1944 9 of of IN cord-014597-66vd2mdu 1944 10 genes gene NNS cord-014597-66vd2mdu 1944 11 that that WDT cord-014597-66vd2mdu 1944 12 are be VBP cord-014597-66vd2mdu 1944 13 required require VBN cord-014597-66vd2mdu 1944 14 for for IN cord-014597-66vd2mdu 1944 15 survival survival NN cord-014597-66vd2mdu 1944 16 might may MD cord-014597-66vd2mdu 1944 17 generate generate VB cord-014597-66vd2mdu 1944 18 additional additional JJ cord-014597-66vd2mdu 1944 19 energy energy NN cord-014597-66vd2mdu 1944 20 for for IN cord-014597-66vd2mdu 1944 21 recombinant recombinant JJ cord-014597-66vd2mdu 1944 22 protein protein NN cord-014597-66vd2mdu 1944 23 production production NN cord-014597-66vd2mdu 1944 24 in in IN cord-014597-66vd2mdu 1944 25 high high JJ cord-014597-66vd2mdu 1944 26 - - HYPH cord-014597-66vd2mdu 1944 27 chromosome chromosome NN cord-014597-66vd2mdu 1944 28 - - HYPH cord-014597-66vd2mdu 1944 29 number number NN cord-014597-66vd2mdu 1944 30 cells cell NNS cord-014597-66vd2mdu 1944 31 . . . cord-014597-66vd2mdu 1945 1 From from IN cord-014597-66vd2mdu 1945 2 an an DT cord-014597-66vd2mdu 1945 3 evolutionary evolutionary JJ cord-014597-66vd2mdu 1945 4 perspective perspective NN cord-014597-66vd2mdu 1945 5 , , , cord-014597-66vd2mdu 1945 6 an an DT cord-014597-66vd2mdu 1945 7 increased increase VBN cord-014597-66vd2mdu 1945 8 set set NN cord-014597-66vd2mdu 1945 9 of of IN cord-014597-66vd2mdu 1945 10 chromosomes chromosome NNS cord-014597-66vd2mdu 1945 11 underlies underlie VBZ cord-014597-66vd2mdu 1945 12 rapid rapid JJ cord-014597-66vd2mdu 1945 13 evolutionary evolutionary JJ cord-014597-66vd2mdu 1945 14 adaptation adaptation NN cord-014597-66vd2mdu 1945 15 . . . cord-014597-66vd2mdu 1946 1 Although although IN cord-014597-66vd2mdu 1946 2 there there EX cord-014597-66vd2mdu 1946 3 are be VBP cord-014597-66vd2mdu 1946 4 issues issue NNS cord-014597-66vd2mdu 1946 5 to to TO cord-014597-66vd2mdu 1946 6 be be VB cord-014597-66vd2mdu 1946 7 considered consider VBN cord-014597-66vd2mdu 1946 8 , , , cord-014597-66vd2mdu 1946 9 such such JJ cord-014597-66vd2mdu 1946 10 as as IN cord-014597-66vd2mdu 1946 11 stability stability NN cord-014597-66vd2mdu 1946 12 , , , cord-014597-66vd2mdu 1946 13 there there EX cord-014597-66vd2mdu 1946 14 may may MD cord-014597-66vd2mdu 1946 15 also also RB cord-014597-66vd2mdu 1946 16 be be VB cord-014597-66vd2mdu 1946 17 advantages advantage NNS cord-014597-66vd2mdu 1946 18 to to IN cord-014597-66vd2mdu 1946 19 using use VBG cord-014597-66vd2mdu 1946 20 high high JJ cord-014597-66vd2mdu 1946 21 - - HYPH cord-014597-66vd2mdu 1946 22 chromosome chromosome NN cord-014597-66vd2mdu 1946 23 - - HYPH cord-014597-66vd2mdu 1946 24 number number NN cord-014597-66vd2mdu 1946 25 aneuploid aneuploid JJ cord-014597-66vd2mdu 1946 26 CHO CHO NNP cord-014597-66vd2mdu 1946 27 cells cell NNS cord-014597-66vd2mdu 1946 28 as as IN cord-014597-66vd2mdu 1946 29 a a DT cord-014597-66vd2mdu 1946 30 production production NN cord-014597-66vd2mdu 1946 31 host host NN cord-014597-66vd2mdu 1946 32 cells cell NNS cord-014597-66vd2mdu 1946 33 of of IN cord-014597-66vd2mdu 1946 34 recombinant recombinant JJ cord-014597-66vd2mdu 1946 35 proteins protein NNS cord-014597-66vd2mdu 1946 36 . . . cord-014597-66vd2mdu 1947 1 Background Background NNP cord-014597-66vd2mdu 1947 2 Human human JJ cord-014597-66vd2mdu 1947 3 growth growth NN cord-014597-66vd2mdu 1947 4 factors factor NNS cord-014597-66vd2mdu 1947 5 have have VBP cord-014597-66vd2mdu 1947 6 an an DT cord-014597-66vd2mdu 1947 7 enormous enormous JJ cord-014597-66vd2mdu 1947 8 therapeutic therapeutic JJ cord-014597-66vd2mdu 1947 9 potential potential NN cord-014597-66vd2mdu 1947 10 . . . cord-014597-66vd2mdu 1948 1 Among among IN cord-014597-66vd2mdu 1948 2 them -PRON- PRP cord-014597-66vd2mdu 1948 3 , , , cord-014597-66vd2mdu 1948 4 the the DT cord-014597-66vd2mdu 1948 5 bone bone NN cord-014597-66vd2mdu 1948 6 morphogenetic morphogenetic JJ cord-014597-66vd2mdu 1948 7 protein-2 protein-2 . cord-014597-66vd2mdu 1948 8 ( ( -LRB- cord-014597-66vd2mdu 1948 9 BMP-2 BMP-2 NNP cord-014597-66vd2mdu 1948 10 ) ) -RRB- cord-014597-66vd2mdu 1948 11 can can MD cord-014597-66vd2mdu 1948 12 induce induce VB cord-014597-66vd2mdu 1948 13 de de FW cord-014597-66vd2mdu 1948 14 novo novo NNP cord-014597-66vd2mdu 1948 15 bone bone NN cord-014597-66vd2mdu 1948 16 formation formation NN cord-014597-66vd2mdu 1948 17 endowing endow VBG cord-014597-66vd2mdu 1948 18 the the DT cord-014597-66vd2mdu 1948 19 protein protein NN cord-014597-66vd2mdu 1948 20 a a DT cord-014597-66vd2mdu 1948 21 high high JJ cord-014597-66vd2mdu 1948 22 therapeutic therapeutic JJ cord-014597-66vd2mdu 1948 23 potential potential NN cord-014597-66vd2mdu 1948 24 . . . cord-014597-66vd2mdu 1949 1 However however RB cord-014597-66vd2mdu 1949 2 , , , cord-014597-66vd2mdu 1949 3 finding find VBG cord-014597-66vd2mdu 1949 4 a a DT cord-014597-66vd2mdu 1949 5 suitable suitable JJ cord-014597-66vd2mdu 1949 6 recombinant recombinant JJ cord-014597-66vd2mdu 1949 7 production production NN cord-014597-66vd2mdu 1949 8 system system NN cord-014597-66vd2mdu 1949 9 for for IN cord-014597-66vd2mdu 1949 10 such such PDT cord-014597-66vd2mdu 1949 11 a a DT cord-014597-66vd2mdu 1949 12 protein protein NN cord-014597-66vd2mdu 1949 13 still still RB cord-014597-66vd2mdu 1949 14 remains remain VBZ cord-014597-66vd2mdu 1949 15 a a DT cord-014597-66vd2mdu 1949 16 challenge challenge NN cord-014597-66vd2mdu 1949 17 . . . cord-014597-66vd2mdu 1950 1 Recombinant recombinant JJ cord-014597-66vd2mdu 1950 2 expression expression NN cord-014597-66vd2mdu 1950 3 of of IN cord-014597-66vd2mdu 1950 4 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1950 5 was be VBD cord-014597-66vd2mdu 1950 6 investigated investigate VBN cord-014597-66vd2mdu 1950 7 in in IN cord-014597-66vd2mdu 1950 8 transiently transiently RB cord-014597-66vd2mdu 1950 9 transfected transfecte VBN cord-014597-66vd2mdu 1950 10 HEK-293 hek-293 JJ cord-014597-66vd2mdu 1950 11 cells cell NNS cord-014597-66vd2mdu 1950 12 and and CC cord-014597-66vd2mdu 1950 13 in in IN cord-014597-66vd2mdu 1950 14 stable stable JJ cord-014597-66vd2mdu 1950 15 clones clone NNS cord-014597-66vd2mdu 1950 16 established establish VBN cord-014597-66vd2mdu 1950 17 in in IN cord-014597-66vd2mdu 1950 18 CHO CHO NNP cord-014597-66vd2mdu 1950 19 - - HYPH cord-014597-66vd2mdu 1950 20 K1 K1 NNP cord-014597-66vd2mdu 1950 21 cells cell NNS cord-014597-66vd2mdu 1950 22 cultivated cultivate VBN cord-014597-66vd2mdu 1950 23 in in IN cord-014597-66vd2mdu 1950 24 ExCell ExCell NNP cord-014597-66vd2mdu 1950 25 and and CC cord-014597-66vd2mdu 1950 26 Pro pro JJ cord-014597-66vd2mdu 1950 27 - - JJ cord-014597-66vd2mdu 1950 28 CHO5 cho5 JJ cord-014597-66vd2mdu 1950 29 medium medium NN cord-014597-66vd2mdu 1950 30 , , , cord-014597-66vd2mdu 1950 31 respectively respectively RB cord-014597-66vd2mdu 1950 32 . . . cord-014597-66vd2mdu 1951 1 Protein protein NN cord-014597-66vd2mdu 1951 2 stability stability NN cord-014597-66vd2mdu 1951 3 and and CC cord-014597-66vd2mdu 1951 4 interaction interaction NN cord-014597-66vd2mdu 1951 5 of of IN cord-014597-66vd2mdu 1951 6 the the DT cord-014597-66vd2mdu 1951 7 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1951 8 with with IN cord-014597-66vd2mdu 1951 9 the the DT cord-014597-66vd2mdu 1951 10 producer producer NN cord-014597-66vd2mdu 1951 11 cells cell NNS cord-014597-66vd2mdu 1951 12 were be VBD cord-014597-66vd2mdu 1951 13 investigated investigate VBN cord-014597-66vd2mdu 1951 14 in in IN cord-014597-66vd2mdu 1951 15 vitro vitro FW cord-014597-66vd2mdu 1951 16 using use VBG cord-014597-66vd2mdu 1951 17 commercially commercially RB cord-014597-66vd2mdu 1951 18 available available JJ cord-014597-66vd2mdu 1951 19 rhBMP2 rhbmp2 NN cord-014597-66vd2mdu 1951 20 . . . cord-014597-66vd2mdu 1952 1 In in IN cord-014597-66vd2mdu 1952 2 addition addition NN cord-014597-66vd2mdu 1952 3 , , , cord-014597-66vd2mdu 1952 4 we -PRON- PRP cord-014597-66vd2mdu 1952 5 investigated investigate VBD cord-014597-66vd2mdu 1952 6 a a DT cord-014597-66vd2mdu 1952 7 cell cell NN cord-014597-66vd2mdu 1952 8 - - HYPH cord-014597-66vd2mdu 1952 9 free free JJ cord-014597-66vd2mdu 1952 10 protein protein NN cord-014597-66vd2mdu 1952 11 synthesis synthesis NN cord-014597-66vd2mdu 1952 12 system system NN cord-014597-66vd2mdu 1952 13 harboring harbor VBG cord-014597-66vd2mdu 1952 14 translocationally translocationally RB cord-014597-66vd2mdu 1952 15 active active JJ cord-014597-66vd2mdu 1952 16 microsomal microsomal JJ cord-014597-66vd2mdu 1952 17 structures structure NNS cord-014597-66vd2mdu 1952 18 , , , cord-014597-66vd2mdu 1952 19 hence hence RB cord-014597-66vd2mdu 1952 20 having have VBG cord-014597-66vd2mdu 1952 21 the the DT cord-014597-66vd2mdu 1952 22 potential potential NN cord-014597-66vd2mdu 1952 23 to to TO cord-014597-66vd2mdu 1952 24 perform perform VB cord-014597-66vd2mdu 1952 25 post post JJ cord-014597-66vd2mdu 1952 26 - - JJ cord-014597-66vd2mdu 1952 27 translational translational JJ cord-014597-66vd2mdu 1952 28 modifications modification NNS cord-014597-66vd2mdu 1952 29 , , , cord-014597-66vd2mdu 1952 30 as as IN cord-014597-66vd2mdu 1952 31 an an DT cord-014597-66vd2mdu 1952 32 alternative alternative JJ cord-014597-66vd2mdu 1952 33 production production NN cord-014597-66vd2mdu 1952 34 method method NN cord-014597-66vd2mdu 1952 35 . . . cord-014597-66vd2mdu 1953 1 We -PRON- PRP cord-014597-66vd2mdu 1953 2 showed show VBD cord-014597-66vd2mdu 1953 3 that that IN cord-014597-66vd2mdu 1953 4 growth growth NN cord-014597-66vd2mdu 1953 5 rates rate NNS cord-014597-66vd2mdu 1953 6 and and CC cord-014597-66vd2mdu 1953 7 viabilities viability NNS cord-014597-66vd2mdu 1953 8 of of IN cord-014597-66vd2mdu 1953 9 the the DT cord-014597-66vd2mdu 1953 10 rhBMP2producing rhBMP2producing NNP cord-014597-66vd2mdu 1953 11 cells cell NNS cord-014597-66vd2mdu 1953 12 were be VBD cord-014597-66vd2mdu 1953 13 similar similar JJ cord-014597-66vd2mdu 1953 14 to to IN cord-014597-66vd2mdu 1953 15 those those DT cord-014597-66vd2mdu 1953 16 of of IN cord-014597-66vd2mdu 1953 17 the the DT cord-014597-66vd2mdu 1953 18 parent parent NN cord-014597-66vd2mdu 1953 19 cell cell NN cord-014597-66vd2mdu 1953 20 line line NN cord-014597-66vd2mdu 1953 21 , , , cord-014597-66vd2mdu 1953 22 while while IN cord-014597-66vd2mdu 1953 23 entry entry NN cord-014597-66vd2mdu 1953 24 into into IN cord-014597-66vd2mdu 1953 25 the the DT cord-014597-66vd2mdu 1953 26 death death NN cord-014597-66vd2mdu 1953 27 phase phase NN cord-014597-66vd2mdu 1953 28 was be VBD cord-014597-66vd2mdu 1953 29 delayed delay VBN cord-014597-66vd2mdu 1953 30 in in IN cord-014597-66vd2mdu 1953 31 case case NN cord-014597-66vd2mdu 1953 32 of of IN cord-014597-66vd2mdu 1953 33 the the DT cord-014597-66vd2mdu 1953 34 recombinant recombinant JJ cord-014597-66vd2mdu 1953 35 cells cell NNS cord-014597-66vd2mdu 1953 36 . . . cord-014597-66vd2mdu 1954 1 The the DT cord-014597-66vd2mdu 1954 2 maximum maximum JJ cord-014597-66vd2mdu 1954 3 rhBMP2 rhbmp2 NN cord-014597-66vd2mdu 1954 4 concentration concentration NN cord-014597-66vd2mdu 1954 5 detected detect VBN cord-014597-66vd2mdu 1954 6 in in IN cord-014597-66vd2mdu 1954 7 the the DT cord-014597-66vd2mdu 1954 8 culture culture NN cord-014597-66vd2mdu 1954 9 supernatant supernatant NN cord-014597-66vd2mdu 1954 10 was be VBD cord-014597-66vd2mdu 1954 11 low low JJ cord-014597-66vd2mdu 1954 12 for for IN cord-014597-66vd2mdu 1954 13 stable stable JJ cord-014597-66vd2mdu 1954 14 clones clone NNS cord-014597-66vd2mdu 1954 15 but but CC cord-014597-66vd2mdu 1954 16 can can MD cord-014597-66vd2mdu 1954 17 be be VB cord-014597-66vd2mdu 1954 18 greatly greatly RB cord-014597-66vd2mdu 1954 19 improved improve VBN cord-014597-66vd2mdu 1954 20 combining combine VBG cord-014597-66vd2mdu 1954 21 the the DT cord-014597-66vd2mdu 1954 22 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1954 23 cells cell NNS cord-014597-66vd2mdu 1954 24 transient transient JJ cord-014597-66vd2mdu 1954 25 expression expression NN cord-014597-66vd2mdu 1954 26 system system NN cord-014597-66vd2mdu 1954 27 and and CC cord-014597-66vd2mdu 1954 28 batch batch NN cord-014597-66vd2mdu 1954 29 reactor reactor NN cord-014597-66vd2mdu 1954 30 cultivation cultivation NN cord-014597-66vd2mdu 1954 31 which which WDT cord-014597-66vd2mdu 1954 32 reflects reflect VBZ cord-014597-66vd2mdu 1954 33 a a DT cord-014597-66vd2mdu 1954 34 better well JJR cord-014597-66vd2mdu 1954 35 compatibility compatibility NN cord-014597-66vd2mdu 1954 36 of of IN cord-014597-66vd2mdu 1954 37 the the DT cord-014597-66vd2mdu 1954 38 codon codon NN cord-014597-66vd2mdu 1954 39 usage usage NN cord-014597-66vd2mdu 1954 40 in in IN cord-014597-66vd2mdu 1954 41 the the DT cord-014597-66vd2mdu 1954 42 human human JJ cord-014597-66vd2mdu 1954 43 cells cell NNS cord-014597-66vd2mdu 1954 44 ( ( -LRB- cord-014597-66vd2mdu 1954 45 Table table NN cord-014597-66vd2mdu 1954 46 1 1 CD cord-014597-66vd2mdu 1954 47 ) ) -RRB- cord-014597-66vd2mdu 1954 48 . . . cord-014597-66vd2mdu 1955 1 hBMP2 hBMP2 NNP cord-014597-66vd2mdu 1956 1 protein protein NN cord-014597-66vd2mdu 1956 2 is be VBZ cord-014597-66vd2mdu 1956 3 sensitive sensitive JJ cord-014597-66vd2mdu 1956 4 to to IN cord-014597-66vd2mdu 1956 5 slightly slightly RB cord-014597-66vd2mdu 1956 6 acidic acidic JJ cord-014597-66vd2mdu 1956 7 pH ph NN cord-014597-66vd2mdu 1956 8 and and CC cord-014597-66vd2mdu 1956 9 to to IN cord-014597-66vd2mdu 1956 10 a a DT cord-014597-66vd2mdu 1956 11 lesser less JJR cord-014597-66vd2mdu 1956 12 extend extend NN cord-014597-66vd2mdu 1956 13 to to IN cord-014597-66vd2mdu 1956 14 proteases protease NNS cord-014597-66vd2mdu 1956 15 ( ( -LRB- cord-014597-66vd2mdu 1956 16 Fig Fig NNP cord-014597-66vd2mdu 1956 17 . . . cord-014597-66vd2mdu 1956 18 1a 1a CD cord-014597-66vd2mdu 1956 19 ) ) -RRB- cord-014597-66vd2mdu 1956 20 and and CC cord-014597-66vd2mdu 1956 21 binds bind VBZ cord-014597-66vd2mdu 1956 22 to to IN cord-014597-66vd2mdu 1956 23 both both DT cord-014597-66vd2mdu 1956 24 producers producer NNS cord-014597-66vd2mdu 1956 25 cell cell NN cord-014597-66vd2mdu 1956 26 lines line NNS cord-014597-66vd2mdu 1956 27 ( ( -LRB- cord-014597-66vd2mdu 1956 28 Fig fig NN cord-014597-66vd2mdu 1956 29 . . . cord-014597-66vd2mdu 1956 30 1b 1b CD cord-014597-66vd2mdu 1956 31 ) ) -RRB- cord-014597-66vd2mdu 1957 1 -All -All : cord-014597-66vd2mdu 1958 1 this this DT cord-014597-66vd2mdu 1958 2 could could MD cord-014597-66vd2mdu 1958 3 incidentally incidentally RB cord-014597-66vd2mdu 1958 4 contribute contribute VB cord-014597-66vd2mdu 1958 5 to to IN cord-014597-66vd2mdu 1958 6 the the DT cord-014597-66vd2mdu 1958 7 low low JJ cord-014597-66vd2mdu 1958 8 product product NN cord-014597-66vd2mdu 1958 9 titers titer NNS cord-014597-66vd2mdu 1958 10 . . . cord-014597-66vd2mdu 1959 1 Cell cell NN cord-014597-66vd2mdu 1959 2 - - HYPH cord-014597-66vd2mdu 1959 3 free free JJ cord-014597-66vd2mdu 1959 4 protein protein NN cord-014597-66vd2mdu 1959 5 synthesis synthesis NN cord-014597-66vd2mdu 1959 6 has have VBZ cord-014597-66vd2mdu 1959 7 been be VBN cord-014597-66vd2mdu 1959 8 proposed propose VBN cord-014597-66vd2mdu 1959 9 as as IN cord-014597-66vd2mdu 1959 10 alternative alternative NN cord-014597-66vd2mdu 1959 11 for for IN cord-014597-66vd2mdu 1959 12 " " `` cord-014597-66vd2mdu 1959 13 difficult difficult JJ cord-014597-66vd2mdu 1959 14 - - HYPH cord-014597-66vd2mdu 1959 15 to to TO cord-014597-66vd2mdu 1959 16 - - HYPH cord-014597-66vd2mdu 1959 17 express express VB cord-014597-66vd2mdu 1959 18 " " '' cord-014597-66vd2mdu 1959 19 proteins protein NNS cord-014597-66vd2mdu 1959 20 . . . cord-014597-66vd2mdu 1960 1 Since since IN cord-014597-66vd2mdu 1960 2 native native JJ cord-014597-66vd2mdu 1960 3 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1960 4 is be VBZ cord-014597-66vd2mdu 1960 5 glycosylated glycosylate VBN cord-014597-66vd2mdu 1960 6 , , , cord-014597-66vd2mdu 1960 7 a a DT cord-014597-66vd2mdu 1960 8 cell cell NN cord-014597-66vd2mdu 1960 9 - - HYPH cord-014597-66vd2mdu 1960 10 free free JJ cord-014597-66vd2mdu 1960 11 system system NN cord-014597-66vd2mdu 1960 12 based base VBN cord-014597-66vd2mdu 1960 13 on on IN cord-014597-66vd2mdu 1960 14 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 1960 15 cell cell NN cord-014597-66vd2mdu 1960 16 lysates lysate NNS cord-014597-66vd2mdu 1960 17 is be VBZ cord-014597-66vd2mdu 1960 18 required require VBN cord-014597-66vd2mdu 1960 19 for for IN cord-014597-66vd2mdu 1960 20 its -PRON- PRP$ cord-014597-66vd2mdu 1960 21 production production NN cord-014597-66vd2mdu 1960 22 . . . cord-014597-66vd2mdu 1961 1 CHO CHO NNP cord-014597-66vd2mdu 1961 2 cell cell NN cord-014597-66vd2mdu 1961 3 lysates lysate NNS cord-014597-66vd2mdu 1961 4 were be VBD cord-014597-66vd2mdu 1961 5 chosen choose VBN cord-014597-66vd2mdu 1961 6 , , , cord-014597-66vd2mdu 1961 7 since since IN cord-014597-66vd2mdu 1961 8 they -PRON- PRP cord-014597-66vd2mdu 1961 9 had have VBD cord-014597-66vd2mdu 1961 10 previously previously RB cord-014597-66vd2mdu 1961 11 been be VBN cord-014597-66vd2mdu 1961 12 established establish VBN cord-014597-66vd2mdu 1961 13 as as IN cord-014597-66vd2mdu 1961 14 the the DT cord-014597-66vd2mdu 1961 15 most most RBS cord-014597-66vd2mdu 1961 16 productive productive JJ cord-014597-66vd2mdu 1961 17 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 1961 18 system system NN cord-014597-66vd2mdu 1961 19 in in IN cord-014597-66vd2mdu 1961 20 our -PRON- PRP$ cord-014597-66vd2mdu 1961 21 hands hand NNS cord-014597-66vd2mdu 1961 22 [ [ -LRB- cord-014597-66vd2mdu 1961 23 1 1 CD cord-014597-66vd2mdu 1961 24 ] ] -RRB- cord-014597-66vd2mdu 1961 25 , , , cord-014597-66vd2mdu 1961 26 while while IN cord-014597-66vd2mdu 1961 27 concomitantly concomitantly RB cord-014597-66vd2mdu 1961 28 enabling enable VBG cord-014597-66vd2mdu 1961 29 a a DT cord-014597-66vd2mdu 1961 30 direct direct JJ cord-014597-66vd2mdu 1961 31 comparison comparison NN cord-014597-66vd2mdu 1961 32 to to IN cord-014597-66vd2mdu 1961 33 the the DT cord-014597-66vd2mdu 1961 34 production production NN cord-014597-66vd2mdu 1961 35 of of IN cord-014597-66vd2mdu 1961 36 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1961 37 in in IN cord-014597-66vd2mdu 1961 38 stable stable JJ cord-014597-66vd2mdu 1961 39 clones clone NNS cord-014597-66vd2mdu 1961 40 established establish VBN cord-014597-66vd2mdu 1961 41 in in IN cord-014597-66vd2mdu 1961 42 CHO CHO NNP cord-014597-66vd2mdu 1961 43 - - HYPH cord-014597-66vd2mdu 1961 44 K1 K1 NNP cord-014597-66vd2mdu 1961 45 . . . cord-014597-66vd2mdu 1962 1 The the DT cord-014597-66vd2mdu 1962 2 ability ability NN cord-014597-66vd2mdu 1962 3 to to TO cord-014597-66vd2mdu 1962 4 perform perform VB cord-014597-66vd2mdu 1962 5 post post JJ cord-014597-66vd2mdu 1962 6 - - JJ cord-014597-66vd2mdu 1962 7 translational translational JJ cord-014597-66vd2mdu 1962 8 modifications modification NNS cord-014597-66vd2mdu 1962 9 is be VBZ cord-014597-66vd2mdu 1962 10 a a DT cord-014597-66vd2mdu 1962 11 major major JJ cord-014597-66vd2mdu 1962 12 advantage advantage NN cord-014597-66vd2mdu 1962 13 of of IN cord-014597-66vd2mdu 1962 14 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 1962 15 systems system NNS cord-014597-66vd2mdu 1962 16 . . . cord-014597-66vd2mdu 1963 1 The the DT cord-014597-66vd2mdu 1963 2 CHO CHO NNP cord-014597-66vd2mdu 1963 3 lysates lysate NNS cord-014597-66vd2mdu 1963 4 prepared prepare VBN cord-014597-66vd2mdu 1963 5 by by IN cord-014597-66vd2mdu 1963 6 the the DT cord-014597-66vd2mdu 1963 7 protocol protocol NN cord-014597-66vd2mdu 1963 8 used use VBN cord-014597-66vd2mdu 1963 9 here here RB cord-014597-66vd2mdu 1963 10 have have VBP cord-014597-66vd2mdu 1963 11 previously previously RB cord-014597-66vd2mdu 1963 12 been be VBN cord-014597-66vd2mdu 1963 13 shown show VBN cord-014597-66vd2mdu 1963 14 to to TO cord-014597-66vd2mdu 1963 15 contain contain VB cord-014597-66vd2mdu 1963 16 significant significant JJ cord-014597-66vd2mdu 1963 17 amounts amount NNS cord-014597-66vd2mdu 1963 18 of of IN cord-014597-66vd2mdu 1963 19 endogenous endogenous JJ cord-014597-66vd2mdu 1963 20 microsomes microsome NNS cord-014597-66vd2mdu 1963 21 derived derive VBN cord-014597-66vd2mdu 1963 22 from from IN cord-014597-66vd2mdu 1963 23 the the DT cord-014597-66vd2mdu 1963 24 endoplasmatic endoplasmatic JJ cord-014597-66vd2mdu 1963 25 reticulum reticulum NN cord-014597-66vd2mdu 1963 26 during during IN cord-014597-66vd2mdu 1963 27 lysis lysis NN cord-014597-66vd2mdu 1963 28 [ [ -LRB- cord-014597-66vd2mdu 1963 29 2 2 CD cord-014597-66vd2mdu 1963 30 ] ] -RRB- cord-014597-66vd2mdu 1963 31 . . . cord-014597-66vd2mdu 1964 1 To to TO cord-014597-66vd2mdu 1964 2 enforce enforce VB cord-014597-66vd2mdu 1964 3 translocation translocation NN cord-014597-66vd2mdu 1964 4 of of IN cord-014597-66vd2mdu 1964 5 the the DT cord-014597-66vd2mdu 1964 6 target target NN cord-014597-66vd2mdu 1964 7 protein protein NN cord-014597-66vd2mdu 1964 8 into into IN cord-014597-66vd2mdu 1964 9 the the DT cord-014597-66vd2mdu 1964 10 microsomal microsomal NNP cord-014597-66vd2mdu 1964 11 structures structure NNS cord-014597-66vd2mdu 1964 12 , , , cord-014597-66vd2mdu 1964 13 a a DT cord-014597-66vd2mdu 1964 14 melittin melittin NNP cord-014597-66vd2mdu 1964 15 signal signal NN cord-014597-66vd2mdu 1964 16 peptide peptide NN cord-014597-66vd2mdu 1964 17 was be VBD cord-014597-66vd2mdu 1964 18 fused fuse VBN cord-014597-66vd2mdu 1964 19 to to IN cord-014597-66vd2mdu 1964 20 the the DT cord-014597-66vd2mdu 1964 21 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1964 22 cDNA cdna NN cord-014597-66vd2mdu 1964 23 . . . cord-014597-66vd2mdu 1965 1 The the DT cord-014597-66vd2mdu 1965 2 glycosylation glycosylation NN cord-014597-66vd2mdu 1965 3 of of IN cord-014597-66vd2mdu 1965 4 the the DT cord-014597-66vd2mdu 1965 5 protein protein NN cord-014597-66vd2mdu 1965 6 was be VBD cord-014597-66vd2mdu 1965 7 assessed assess VBN cord-014597-66vd2mdu 1965 8 by by IN cord-014597-66vd2mdu 1965 9 enzymatic enzymatic JJ cord-014597-66vd2mdu 1965 10 treatment treatment NN cord-014597-66vd2mdu 1965 11 ( ( -LRB- cord-014597-66vd2mdu 1965 12 PNGase PNGase NNP cord-014597-66vd2mdu 1965 13 , , , cord-014597-66vd2mdu 1965 14 EndoH EndoH NNP cord-014597-66vd2mdu 1965 15 ) ) -RRB- cord-014597-66vd2mdu 1965 16 and and CC cord-014597-66vd2mdu 1965 17 confirmed confirm VBD cord-014597-66vd2mdu 1965 18 using use VBG cord-014597-66vd2mdu 1965 19 14 14 CD cord-014597-66vd2mdu 1965 20 C c NN cord-014597-66vd2mdu 1965 21 - - HYPH cord-014597-66vd2mdu 1965 22 mannose mannose NN cord-014597-66vd2mdu 1965 23 for for IN cord-014597-66vd2mdu 1965 24 the the DT cord-014597-66vd2mdu 1965 25 de de NNP cord-014597-66vd2mdu 1965 26 novo novo NNP cord-014597-66vd2mdu 1965 27 protein protein NNP cord-014597-66vd2mdu 1965 28 synthesis synthesis NN cord-014597-66vd2mdu 1965 29 . . . cord-014597-66vd2mdu 1966 1 Upon upon IN cord-014597-66vd2mdu 1966 2 cell cell NN cord-014597-66vd2mdu 1966 3 - - HYPH cord-014597-66vd2mdu 1966 4 free free JJ cord-014597-66vd2mdu 1966 5 protein protein NN cord-014597-66vd2mdu 1966 6 synthesis synthesis NN cord-014597-66vd2mdu 1966 7 , , , cord-014597-66vd2mdu 1966 8 the the DT cord-014597-66vd2mdu 1966 9 hBMP2 hbmp2 NN cord-014597-66vd2mdu 1966 10 yield yield NN cord-014597-66vd2mdu 1966 11 was be VBD cord-014597-66vd2mdu 1966 12 100-fold 100-fold CD cord-014597-66vd2mdu 1966 13 higher high JJR cord-014597-66vd2mdu 1966 14 than than IN cord-014597-66vd2mdu 1966 15 the the DT cord-014597-66vd2mdu 1966 16 best good JJS cord-014597-66vd2mdu 1966 17 one one CD cord-014597-66vd2mdu 1966 18 in in IN cord-014597-66vd2mdu 1966 19 the the DT cord-014597-66vd2mdu 1966 20 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 1966 21 cells cell NNS cord-014597-66vd2mdu 1966 22 . . . cord-014597-66vd2mdu 1967 1 The the DT cord-014597-66vd2mdu 1967 2 difference difference NN cord-014597-66vd2mdu 1967 3 becomes become VBZ cord-014597-66vd2mdu 1967 4 even even RB cord-014597-66vd2mdu 1967 5 more more RBR cord-014597-66vd2mdu 1967 6 dramatic dramatic JJ cord-014597-66vd2mdu 1967 7 , , , cord-014597-66vd2mdu 1967 8 when when WRB cord-014597-66vd2mdu 1967 9 productivities productivity NNS cord-014597-66vd2mdu 1967 10 are be VBP cord-014597-66vd2mdu 1967 11 considered consider VBN cord-014597-66vd2mdu 1967 12 ( ( -LRB- cord-014597-66vd2mdu 1967 13 Table table NN cord-014597-66vd2mdu 1967 14 1 1 CD cord-014597-66vd2mdu 1967 15 ) ) -RRB- cord-014597-66vd2mdu 1967 16 , , , cord-014597-66vd2mdu 1967 17 i.e. i.e. FW cord-014597-66vd2mdu 1967 18 the the DT cord-014597-66vd2mdu 1967 19 fact fact NN cord-014597-66vd2mdu 1967 20 that that IN cord-014597-66vd2mdu 1967 21 maximum maximum JJ cord-014597-66vd2mdu 1967 22 product product NN cord-014597-66vd2mdu 1967 23 titers titer NNS cord-014597-66vd2mdu 1967 24 are be VBP cord-014597-66vd2mdu 1967 25 reached reach VBN cord-014597-66vd2mdu 1967 26 within within IN cord-014597-66vd2mdu 1967 27 3 3 CD cord-014597-66vd2mdu 1967 28 h h NN cord-014597-66vd2mdu 1967 29 in in IN cord-014597-66vd2mdu 1967 30 the the DT cord-014597-66vd2mdu 1967 31 cellfree cellfree NNP cord-014597-66vd2mdu 1967 32 system system NN cord-014597-66vd2mdu 1967 33 compared compare VBN cord-014597-66vd2mdu 1967 34 to to IN cord-014597-66vd2mdu 1967 35 120 120 CD cord-014597-66vd2mdu 1967 36 h h NN cord-014597-66vd2mdu 1967 37 in in IN cord-014597-66vd2mdu 1967 38 the the DT cord-014597-66vd2mdu 1967 39 cell cell NN cord-014597-66vd2mdu 1967 40 - - HYPH cord-014597-66vd2mdu 1967 41 based base VBN cord-014597-66vd2mdu 1967 42 ones one NNS cord-014597-66vd2mdu 1967 43 . . . cord-014597-66vd2mdu 1968 1 This this DT cord-014597-66vd2mdu 1968 2 demonstrates demonstrate VBZ cord-014597-66vd2mdu 1968 3 that that IN cord-014597-66vd2mdu 1968 4 the the DT cord-014597-66vd2mdu 1968 5 cell cell NN cord-014597-66vd2mdu 1968 6 - - HYPH cord-014597-66vd2mdu 1968 7 free free JJ cord-014597-66vd2mdu 1968 8 expression expression NN cord-014597-66vd2mdu 1968 9 system system NN cord-014597-66vd2mdu 1968 10 is be VBZ cord-014597-66vd2mdu 1968 11 most most RBS cord-014597-66vd2mdu 1968 12 suitable suitable JJ cord-014597-66vd2mdu 1968 13 compared compare VBN cord-014597-66vd2mdu 1968 14 to to IN cord-014597-66vd2mdu 1968 15 mammalian mammalian JJ cord-014597-66vd2mdu 1968 16 cell cell NN cord-014597-66vd2mdu 1968 17 expression expression NN cord-014597-66vd2mdu 1968 18 method method NN cord-014597-66vd2mdu 1968 19 for for IN cord-014597-66vd2mdu 1968 20 the the DT cord-014597-66vd2mdu 1968 21 production production NN cord-014597-66vd2mdu 1968 22 of of IN cord-014597-66vd2mdu 1968 23 glycosylated glycosylated JJ cord-014597-66vd2mdu 1968 24 human human JJ cord-014597-66vd2mdu 1968 25 BMP2 BMP2 NNP cord-014597-66vd2mdu 1968 26 ( ( -LRB- cord-014597-66vd2mdu 1968 27 Table table NN cord-014597-66vd2mdu 1968 28 1 1 CD cord-014597-66vd2mdu 1968 29 ) ) -RRB- cord-014597-66vd2mdu 1968 30 [ [ -LRB- cord-014597-66vd2mdu 1968 31 3 3 CD cord-014597-66vd2mdu 1968 32 ] ] -RRB- cord-014597-66vd2mdu 1968 33 . . . cord-014597-66vd2mdu 1969 1 Human human JJ cord-014597-66vd2mdu 1969 2 growth growth NN cord-014597-66vd2mdu 1969 3 factors factor NNS cord-014597-66vd2mdu 1969 4 are be VBP cord-014597-66vd2mdu 1969 5 complex complex JJ cord-014597-66vd2mdu 1969 6 molecules molecule NNS cord-014597-66vd2mdu 1969 7 , , , cord-014597-66vd2mdu 1969 8 which which WDT cord-014597-66vd2mdu 1969 9 make make VBP cord-014597-66vd2mdu 1969 10 their -PRON- PRP$ cord-014597-66vd2mdu 1969 11 production production NN cord-014597-66vd2mdu 1969 12 in in IN cord-014597-66vd2mdu 1969 13 mammalian mammalian JJ cord-014597-66vd2mdu 1969 14 cells cell NNS cord-014597-66vd2mdu 1969 15 desirable desirable JJ cord-014597-66vd2mdu 1969 16 . . . cord-014597-66vd2mdu 1970 1 However however RB cord-014597-66vd2mdu 1970 2 , , , cord-014597-66vd2mdu 1970 3 low low JJ cord-014597-66vd2mdu 1970 4 product product NN cord-014597-66vd2mdu 1970 5 titers titer NNS cord-014597-66vd2mdu 1970 6 caused cause VBN cord-014597-66vd2mdu 1970 7 by by IN cord-014597-66vd2mdu 1970 8 a a DT cord-014597-66vd2mdu 1970 9 variety variety NN cord-014597-66vd2mdu 1970 10 of of IN cord-014597-66vd2mdu 1970 11 both both DT cord-014597-66vd2mdu 1970 12 cell cell NN cord-014597-66vd2mdu 1970 13 and and CC cord-014597-66vd2mdu 1970 14 process process NN cord-014597-66vd2mdu 1970 15 related relate VBN cord-014597-66vd2mdu 1970 16 effects effect NNS cord-014597-66vd2mdu 1970 17 may may MD cord-014597-66vd2mdu 1970 18 hinder hinder VB cord-014597-66vd2mdu 1970 19 the the DT cord-014597-66vd2mdu 1970 20 development development NN cord-014597-66vd2mdu 1970 21 of of IN cord-014597-66vd2mdu 1970 22 highly highly RB cord-014597-66vd2mdu 1970 23 productive productive JJ cord-014597-66vd2mdu 1970 24 processes process NNS cord-014597-66vd2mdu 1970 25 . . . cord-014597-66vd2mdu 1971 1 In in IN cord-014597-66vd2mdu 1971 2 such such JJ cord-014597-66vd2mdu 1971 3 cases case NNS cord-014597-66vd2mdu 1971 4 , , , cord-014597-66vd2mdu 1971 5 cell cell NN cord-014597-66vd2mdu 1971 6 - - HYPH cord-014597-66vd2mdu 1971 7 free free JJ cord-014597-66vd2mdu 1971 8 protein protein NN cord-014597-66vd2mdu 1971 9 production production NN cord-014597-66vd2mdu 1971 10 using use VBG cord-014597-66vd2mdu 1971 11 CHO CHO NNP cord-014597-66vd2mdu 1971 12 cell cell NN cord-014597-66vd2mdu 1971 13 lysates lysate NNS cord-014597-66vd2mdu 1971 14 containing contain VBG cord-014597-66vd2mdu 1971 15 endogenous endogenous JJ cord-014597-66vd2mdu 1971 16 microsomes microsome NNS cord-014597-66vd2mdu 1971 17 for for IN cord-014597-66vd2mdu 1971 18 posttranslational posttranslational JJ cord-014597-66vd2mdu 1971 19 processing processing NN cord-014597-66vd2mdu 1971 20 , , , cord-014597-66vd2mdu 1971 21 may may MD cord-014597-66vd2mdu 1971 22 eventually eventually RB cord-014597-66vd2mdu 1971 23 present present VB cord-014597-66vd2mdu 1971 24 an an DT cord-014597-66vd2mdu 1971 25 attractive attractive JJ cord-014597-66vd2mdu 1971 26 alternative alternative NN cord-014597-66vd2mdu 1971 27 . . . cord-014597-66vd2mdu 1972 1 In in IN cord-014597-66vd2mdu 1972 2 particular particular JJ cord-014597-66vd2mdu 1972 3 since since IN cord-014597-66vd2mdu 1972 4 these these DT cord-014597-66vd2mdu 1972 5 lysates lysate NNS cord-014597-66vd2mdu 1972 6 can can MD cord-014597-66vd2mdu 1972 7 be be VB cord-014597-66vd2mdu 1972 8 used use VBN cord-014597-66vd2mdu 1972 9 under under IN cord-014597-66vd2mdu 1972 10 tightly tightly RB cord-014597-66vd2mdu 1972 11 controlled control VBN cord-014597-66vd2mdu 1972 12 conditions condition NNS cord-014597-66vd2mdu 1972 13 assuring assure VBG cord-014597-66vd2mdu 1972 14 a a DT cord-014597-66vd2mdu 1972 15 higher high JJR cord-014597-66vd2mdu 1972 16 degree degree NN cord-014597-66vd2mdu 1972 17 of of IN cord-014597-66vd2mdu 1972 18 reproducibility reproducibility NN cord-014597-66vd2mdu 1972 19 , , , cord-014597-66vd2mdu 1972 20 than than IN cord-014597-66vd2mdu 1972 21 , , , cord-014597-66vd2mdu 1972 22 e.g. e.g. IN cord-014597-66vd2mdu 1972 23 transient transient JJ cord-014597-66vd2mdu 1972 24 transfection transfection NN cord-014597-66vd2mdu 1972 25 systems system NNS cord-014597-66vd2mdu 1972 26 . . . cord-014597-66vd2mdu 1973 1 Cell cell NN cord-014597-66vd2mdu 1973 2 - - HYPH cord-014597-66vd2mdu 1973 3 free free JJ cord-014597-66vd2mdu 1973 4 systems system NNS cord-014597-66vd2mdu 1973 5 are be VBP cord-014597-66vd2mdu 1973 6 known know VBN cord-014597-66vd2mdu 1973 7 to to TO cord-014597-66vd2mdu 1973 8 circumvent circumvent VB cord-014597-66vd2mdu 1973 9 typical typical JJ cord-014597-66vd2mdu 1973 10 bottlenecks bottleneck NNS cord-014597-66vd2mdu 1973 11 of of IN cord-014597-66vd2mdu 1973 12 cellbased cellbased JJ cord-014597-66vd2mdu 1973 13 ones one NNS cord-014597-66vd2mdu 1973 14 , , , cord-014597-66vd2mdu 1973 15 e.g. e.g. DT cord-014597-66vd2mdu 1973 16 metabolic metabolic JJ cord-014597-66vd2mdu 1973 17 regulation regulation NN cord-014597-66vd2mdu 1973 18 and and CC cord-014597-66vd2mdu 1973 19 cell cell NN cord-014597-66vd2mdu 1973 20 maintenance maintenance NN cord-014597-66vd2mdu 1973 21 mechanisms mechanism NNS cord-014597-66vd2mdu 1973 22 . . . cord-014597-66vd2mdu 1974 1 In in IN cord-014597-66vd2mdu 1974 2 consequence consequence NN cord-014597-66vd2mdu 1974 3 , , , cord-014597-66vd2mdu 1974 4 the the DT cord-014597-66vd2mdu 1974 5 production production NN cord-014597-66vd2mdu 1974 6 of of IN cord-014597-66vd2mdu 1974 7 a a DT cord-014597-66vd2mdu 1974 8 recombinant recombinant JJ cord-014597-66vd2mdu 1974 9 protein protein NN cord-014597-66vd2mdu 1974 10 is be VBZ cord-014597-66vd2mdu 1974 11 neither neither CC cord-014597-66vd2mdu 1974 12 inhibited inhibit VBN cord-014597-66vd2mdu 1974 13 by by IN cord-014597-66vd2mdu 1974 14 its -PRON- PRP$ cord-014597-66vd2mdu 1974 15 accumulation accumulation NN cord-014597-66vd2mdu 1974 16 nor nor CC cord-014597-66vd2mdu 1974 17 by by IN cord-014597-66vd2mdu 1974 18 any any DT cord-014597-66vd2mdu 1974 19 interaction interaction NN cord-014597-66vd2mdu 1974 20 with with IN cord-014597-66vd2mdu 1974 21 the the DT cord-014597-66vd2mdu 1974 22 cells cell NNS cord-014597-66vd2mdu 1974 23 , , , cord-014597-66vd2mdu 1974 24 e.g. e.g. RB cord-014597-66vd2mdu 1974 25 through through IN cord-014597-66vd2mdu 1974 26 the the DT cord-014597-66vd2mdu 1974 27 activation activation NN cord-014597-66vd2mdu 1974 28 of of IN cord-014597-66vd2mdu 1974 29 inhibitory inhibitory JJ cord-014597-66vd2mdu 1974 30 signaling signal VBG cord-014597-66vd2mdu 1974 31 pathways pathway NNS cord-014597-66vd2mdu 1974 32 . . . cord-014597-66vd2mdu 1975 1 core core NN cord-014597-66vd2mdu 1975 2 . . . cord-014597-66vd2mdu 1976 1 Preliminary preliminary JJ cord-014597-66vd2mdu 1976 2 studies study NNS cord-014597-66vd2mdu 1976 3 showed show VBD cord-014597-66vd2mdu 1976 4 that that IN cord-014597-66vd2mdu 1976 5 the the DT cord-014597-66vd2mdu 1976 6 corresponding correspond VBG cord-014597-66vd2mdu 1976 7 polyplexes polyplexes NN cord-014597-66vd2mdu 1976 8 , , , cord-014597-66vd2mdu 1976 9 but but CC cord-014597-66vd2mdu 1976 10 also also RB cord-014597-66vd2mdu 1976 11 some some DT cord-014597-66vd2mdu 1976 12 of of IN cord-014597-66vd2mdu 1976 13 the the DT cord-014597-66vd2mdu 1976 14 cells cell NNS cord-014597-66vd2mdu 1976 15 that that WDT cord-014597-66vd2mdu 1976 16 came come VBD cord-014597-66vd2mdu 1976 17 into into IN cord-014597-66vd2mdu 1976 18 contact contact NN cord-014597-66vd2mdu 1976 19 with with IN cord-014597-66vd2mdu 1976 20 them -PRON- PRP cord-014597-66vd2mdu 1976 21 , , , cord-014597-66vd2mdu 1976 22 became become VBD cord-014597-66vd2mdu 1976 23 magnetic magnetic JJ cord-014597-66vd2mdu 1976 24 and and CC cord-014597-66vd2mdu 1976 25 were be VBD cord-014597-66vd2mdu 1976 26 manageable manageable JJ cord-014597-66vd2mdu 1976 27 by by IN cord-014597-66vd2mdu 1976 28 magnetic magnetic JJ cord-014597-66vd2mdu 1976 29 fields field NNS cord-014597-66vd2mdu 1976 30 [ [ -LRB- cord-014597-66vd2mdu 1976 31 1 1 CD cord-014597-66vd2mdu 1976 32 ] ] -RRB- cord-014597-66vd2mdu 1976 33 [ [ -LRB- cord-014597-66vd2mdu 1976 34 2 2 CD cord-014597-66vd2mdu 1976 35 ] ] -RRB- cord-014597-66vd2mdu 1976 36 [ [ -LRB- cord-014597-66vd2mdu 1976 37 3 3 CD cord-014597-66vd2mdu 1976 38 ] ] -RRB- cord-014597-66vd2mdu 1976 39 . . . cord-014597-66vd2mdu 1977 1 Here here RB cord-014597-66vd2mdu 1977 2 , , , cord-014597-66vd2mdu 1977 3 we -PRON- PRP cord-014597-66vd2mdu 1977 4 present present VBP cord-014597-66vd2mdu 1977 5 a a DT cord-014597-66vd2mdu 1977 6 characterization characterization NN cord-014597-66vd2mdu 1977 7 of of IN cord-014597-66vd2mdu 1977 8 the the DT cord-014597-66vd2mdu 1977 9 influence influence NN cord-014597-66vd2mdu 1977 10 of of IN cord-014597-66vd2mdu 1977 11 structure structure NN cord-014597-66vd2mdu 1977 12 and and CC cord-014597-66vd2mdu 1977 13 composition composition NN cord-014597-66vd2mdu 1977 14 on on IN cord-014597-66vd2mdu 1977 15 the the DT cord-014597-66vd2mdu 1977 16 function function NN cord-014597-66vd2mdu 1977 17 of of IN cord-014597-66vd2mdu 1977 18 these these DT cord-014597-66vd2mdu 1977 19 polymers polymer NNS cord-014597-66vd2mdu 1977 20 using use VBG cord-014597-66vd2mdu 1977 21 a a DT cord-014597-66vd2mdu 1977 22 library library NN cord-014597-66vd2mdu 1977 23 of of IN cord-014597-66vd2mdu 1977 24 highly highly RB cord-014597-66vd2mdu 1977 25 homogeneous homogeneous JJ cord-014597-66vd2mdu 1977 26 , , , cord-014597-66vd2mdu 1977 27 paramagnetic paramagnetic JJ cord-014597-66vd2mdu 1977 28 nano nano NN cord-014597-66vd2mdu 1977 29 - - HYPH cord-014597-66vd2mdu 1977 30 stars star NNS cord-014597-66vd2mdu 1977 31 with with IN cord-014597-66vd2mdu 1977 32 varied varied JJ cord-014597-66vd2mdu 1977 33 arm arm NN cord-014597-66vd2mdu 1977 34 lengths length NNS cord-014597-66vd2mdu 1977 35 and and CC cord-014597-66vd2mdu 1977 36 densities density NNS cord-014597-66vd2mdu 1977 37 [ [ -LRB- cord-014597-66vd2mdu 1977 38 4 4 CD cord-014597-66vd2mdu 1977 39 ] ] -RRB- cord-014597-66vd2mdu 1977 40 . . . cord-014597-66vd2mdu 1978 1 The the DT cord-014597-66vd2mdu 1978 2 paramagnetic paramagnetic JJ cord-014597-66vd2mdu 1978 3 nano nano NN cord-014597-66vd2mdu 1978 4 - - HYPH cord-014597-66vd2mdu 1978 5 stars star NNS cord-014597-66vd2mdu 1978 6 library library NN cord-014597-66vd2mdu 1978 7 was be VBD cord-014597-66vd2mdu 1978 8 synthesized synthesize VBN cord-014597-66vd2mdu 1978 9 by by IN cord-014597-66vd2mdu 1978 10 coating coat VBG cord-014597-66vd2mdu 1978 11 maghemite maghemite VBN cord-014597-66vd2mdu 1978 12 nanoparticles nanoparticle NNS cord-014597-66vd2mdu 1978 13 ( ( -LRB- cord-014597-66vd2mdu 1978 14 γ γ NN cord-014597-66vd2mdu 1978 15 - - HYPH cord-014597-66vd2mdu 1978 16 Fe Fe NNP cord-014597-66vd2mdu 1978 17 2 2 CD cord-014597-66vd2mdu 1978 18 O o NN cord-014597-66vd2mdu 1978 19 3 3 CD cord-014597-66vd2mdu 1978 20 ) ) -RRB- cord-014597-66vd2mdu 1978 21 with with IN cord-014597-66vd2mdu 1978 22 a a DT cord-014597-66vd2mdu 1978 23 thin thin JJ cord-014597-66vd2mdu 1978 24 silica silica NN cord-014597-66vd2mdu 1978 25 - - HYPH cord-014597-66vd2mdu 1978 26 shell shell NN cord-014597-66vd2mdu 1978 27 functionalized functionalize VBN cord-014597-66vd2mdu 1978 28 with with IN cord-014597-66vd2mdu 1978 29 an an DT cord-014597-66vd2mdu 1978 30 atomic atomic JJ cord-014597-66vd2mdu 1978 31 transfer transfer NN cord-014597-66vd2mdu 1978 32 radical radical JJ cord-014597-66vd2mdu 1978 33 polymerization polymerization NN cord-014597-66vd2mdu 1978 34 ( ( -LRB- cord-014597-66vd2mdu 1978 35 ATRP ATRP NNP cord-014597-66vd2mdu 1978 36 ) ) -RRB- cord-014597-66vd2mdu 1978 37 initiator initiator NN cord-014597-66vd2mdu 1978 38 . . . cord-014597-66vd2mdu 1979 1 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 1979 2 arms arm NNS cord-014597-66vd2mdu 1979 3 were be VBD cord-014597-66vd2mdu 1979 4 grown grow VBN cord-014597-66vd2mdu 1979 5 from from IN cord-014597-66vd2mdu 1979 6 the the DT cord-014597-66vd2mdu 1979 7 core core NN cord-014597-66vd2mdu 1979 8 particles particle NNS cord-014597-66vd2mdu 1979 9 via via IN cord-014597-66vd2mdu 1979 10 ATRP ATRP NNP cord-014597-66vd2mdu 1979 11 . . . cord-014597-66vd2mdu 1980 1 In in IN cord-014597-66vd2mdu 1980 2 one one CD cord-014597-66vd2mdu 1980 3 case case NN cord-014597-66vd2mdu 1980 4 , , , cord-014597-66vd2mdu 1980 5 the the DT cord-014597-66vd2mdu 1980 6 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 1980 7 arms arm NNS cord-014597-66vd2mdu 1980 8 was be VBD cord-014597-66vd2mdu 1980 9 end end NN cord-014597-66vd2mdu 1980 10 - - HYPH cord-014597-66vd2mdu 1980 11 capped cap VBN cord-014597-66vd2mdu 1980 12 with with IN cord-014597-66vd2mdu 1980 13 PDEGMA PDEGMA NNP cord-014597-66vd2mdu 1980 14 blocks block NNS cord-014597-66vd2mdu 1980 15 produced produce VBN cord-014597-66vd2mdu 1980 16 during during IN cord-014597-66vd2mdu 1980 17 a a DT cord-014597-66vd2mdu 1980 18 second second JJ cord-014597-66vd2mdu 1980 19 ATRP ATRP NNP cord-014597-66vd2mdu 1980 20 step step NN cord-014597-66vd2mdu 1980 21 . . . cord-014597-66vd2mdu 1981 1 All all DT cord-014597-66vd2mdu 1981 2 nanostars nanostar NNS cord-014597-66vd2mdu 1981 3 were be VBD cord-014597-66vd2mdu 1981 4 characterized characterize VBN cord-014597-66vd2mdu 1981 5 by by IN cord-014597-66vd2mdu 1981 6 size size NN cord-014597-66vd2mdu 1981 7 exclusion exclusion NN cord-014597-66vd2mdu 1981 8 chromatography chromatography NN cord-014597-66vd2mdu 1981 9 and and CC cord-014597-66vd2mdu 1981 10 thermogravimetry thermogravimetry NNP cord-014597-66vd2mdu 1981 11 to to TO cord-014597-66vd2mdu 1981 12 calculate calculate VB cord-014597-66vd2mdu 1981 13 number number NN cord-014597-66vd2mdu 1981 14 and and CC cord-014597-66vd2mdu 1981 15 length length NN cord-014597-66vd2mdu 1981 16 of of IN cord-014597-66vd2mdu 1981 17 the the DT cord-014597-66vd2mdu 1981 18 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 1981 19 arms arm NNS cord-014597-66vd2mdu 1981 20 . . . cord-014597-66vd2mdu 1982 1 The the DT cord-014597-66vd2mdu 1982 2 core core NN cord-014597-66vd2mdu 1982 3 diameter diameter NN cord-014597-66vd2mdu 1982 4 was be VBD cord-014597-66vd2mdu 1982 5 determined determine VBN cord-014597-66vd2mdu 1982 6 by by IN cord-014597-66vd2mdu 1982 7 transmission transmission NN cord-014597-66vd2mdu 1982 8 electron electron NN cord-014597-66vd2mdu 1982 9 microscopy microscopy NN cord-014597-66vd2mdu 1982 10 and and CC cord-014597-66vd2mdu 1982 11 dynamic dynamic JJ cord-014597-66vd2mdu 1982 12 light light JJ cord-014597-66vd2mdu 1982 13 scattering scattering NN cord-014597-66vd2mdu 1982 14 ( ( -LRB- cord-014597-66vd2mdu 1982 15 DLS DLS NNP cord-014597-66vd2mdu 1982 16 ) ) -RRB- cord-014597-66vd2mdu 1982 17 . . . cord-014597-66vd2mdu 1983 1 The the DT cord-014597-66vd2mdu 1983 2 different different JJ cord-014597-66vd2mdu 1983 3 variants variant NNS cord-014597-66vd2mdu 1983 4 ( ( -LRB- cord-014597-66vd2mdu 1983 5 Table table NN cord-014597-66vd2mdu 1983 6 1 1 CD cord-014597-66vd2mdu 1983 7 ) ) -RRB- cord-014597-66vd2mdu 1983 8 were be VBD cord-014597-66vd2mdu 1983 9 analyzed analyze VBN cord-014597-66vd2mdu 1983 10 for for IN cord-014597-66vd2mdu 1983 11 their -PRON- PRP$ cord-014597-66vd2mdu 1983 12 ability ability NN cord-014597-66vd2mdu 1983 13 to to TO cord-014597-66vd2mdu 1983 14 complex complex VB cord-014597-66vd2mdu 1983 15 pDNA pdna RB cord-014597-66vd2mdu 1983 16 ( ( -LRB- cord-014597-66vd2mdu 1983 17 pEGFP pEGFP NNP cord-014597-66vd2mdu 1983 18 - - HYPH cord-014597-66vd2mdu 1983 19 N1 N1 NNP cord-014597-66vd2mdu 1983 20 ) ) -RRB- cord-014597-66vd2mdu 1983 21 using use VBG cord-014597-66vd2mdu 1983 22 various various JJ cord-014597-66vd2mdu 1983 23 physicochemical physicochemical JJ cord-014597-66vd2mdu 1983 24 methods method NNS cord-014597-66vd2mdu 1983 25 ( ( -LRB- cord-014597-66vd2mdu 1983 26 DLS DLS NNP cord-014597-66vd2mdu 1983 27 , , , cord-014597-66vd2mdu 1983 28 Zeta Zeta NNP cord-014597-66vd2mdu 1983 29 sizer sizer NN cord-014597-66vd2mdu 1983 30 ) ) -RRB- cord-014597-66vd2mdu 1983 31 . . . cord-014597-66vd2mdu 1984 1 Transfection transfection NN cord-014597-66vd2mdu 1984 2 efficiency efficiency NN cord-014597-66vd2mdu 1984 3 / / SYM cord-014597-66vd2mdu 1984 4 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 1984 5 in in IN cord-014597-66vd2mdu 1984 6 CHO CHO NNP cord-014597-66vd2mdu 1984 7 - - HYPH cord-014597-66vd2mdu 1984 8 K1 K1 NNP cord-014597-66vd2mdu 1984 9 cells cell NNS cord-014597-66vd2mdu 1984 10 were be VBD cord-014597-66vd2mdu 1984 11 determined determine VBN cord-014597-66vd2mdu 1984 12 by by IN cord-014597-66vd2mdu 1984 13 flow flow NN cord-014597-66vd2mdu 1984 14 cytometry cytometry NN cord-014597-66vd2mdu 1984 15 . . . cord-014597-66vd2mdu 1985 1 Transfected transfected JJ cord-014597-66vd2mdu 1985 2 cells cell NNS cord-014597-66vd2mdu 1985 3 were be VBD cord-014597-66vd2mdu 1985 4 placed place VBN cord-014597-66vd2mdu 1985 5 in in IN cord-014597-66vd2mdu 1985 6 a a DT cord-014597-66vd2mdu 1985 7 magnetic magnetic JJ cord-014597-66vd2mdu 1985 8 field field NN cord-014597-66vd2mdu 1985 9 and and CC cord-014597-66vd2mdu 1985 10 the the DT cord-014597-66vd2mdu 1985 11 influence influence NN cord-014597-66vd2mdu 1985 12 of of IN cord-014597-66vd2mdu 1985 13 the the DT cord-014597-66vd2mdu 1985 14 polymer polymer NN cord-014597-66vd2mdu 1985 15 architecture architecture NN cord-014597-66vd2mdu 1985 16 on on IN cord-014597-66vd2mdu 1985 17 the the DT cord-014597-66vd2mdu 1985 18 magnetic magnetic JJ cord-014597-66vd2mdu 1985 19 separation separation NN cord-014597-66vd2mdu 1985 20 was be VBD cord-014597-66vd2mdu 1985 21 investigated investigate VBN cord-014597-66vd2mdu 1985 22 . . . cord-014597-66vd2mdu 1986 1 Nonparametric Nonparametric NNP cord-014597-66vd2mdu 1986 2 Spearman Spearman NNP cord-014597-66vd2mdu 1986 3 analysis analysis NN cord-014597-66vd2mdu 1986 4 was be VBD cord-014597-66vd2mdu 1986 5 used use VBN cord-014597-66vd2mdu 1986 6 to to TO cord-014597-66vd2mdu 1986 7 correlate correlate VB cord-014597-66vd2mdu 1986 8 between between IN cord-014597-66vd2mdu 1986 9 arm arm NN cord-014597-66vd2mdu 1986 10 length length NN cord-014597-66vd2mdu 1986 11 / / SYM cord-014597-66vd2mdu 1986 12 arm arm NN cord-014597-66vd2mdu 1986 13 densities density NNS cord-014597-66vd2mdu 1986 14 , , , cord-014597-66vd2mdu 1986 15 magnetic magnetic JJ cord-014597-66vd2mdu 1986 16 properties property NNS cord-014597-66vd2mdu 1986 17 of of IN cord-014597-66vd2mdu 1986 18 the the DT cord-014597-66vd2mdu 1986 19 cells cell NNS cord-014597-66vd2mdu 1986 20 and and CC cord-014597-66vd2mdu 1986 21 transfection transfection NN cord-014597-66vd2mdu 1986 22 efficiency efficiency NN cord-014597-66vd2mdu 1986 23 . . . cord-014597-66vd2mdu 1987 1 Based base VBN cord-014597-66vd2mdu 1987 2 on on IN cord-014597-66vd2mdu 1987 3 the the DT cord-014597-66vd2mdu 1987 4 hydrodynamic hydrodynamic JJ cord-014597-66vd2mdu 1987 5 radii radius NNS cord-014597-66vd2mdu 1987 6 of of IN cord-014597-66vd2mdu 1987 7 the the DT cord-014597-66vd2mdu 1987 8 polyplexes polyplexe NNS cord-014597-66vd2mdu 1987 9 , , , cord-014597-66vd2mdu 1987 10 the the DT cord-014597-66vd2mdu 1987 11 investigated investigate VBN cord-014597-66vd2mdu 1987 12 nano nano NN cord-014597-66vd2mdu 1987 13 - - HYPH cord-014597-66vd2mdu 1987 14 stars star NNS cord-014597-66vd2mdu 1987 15 could could MD cord-014597-66vd2mdu 1987 16 be be VB cord-014597-66vd2mdu 1987 17 divided divide VBN cord-014597-66vd2mdu 1987 18 into into IN cord-014597-66vd2mdu 1987 19 three three CD cord-014597-66vd2mdu 1987 20 subgroups subgroup NNS cord-014597-66vd2mdu 1987 21 ( ( -LRB- cord-014597-66vd2mdu 1987 22 Table table NN cord-014597-66vd2mdu 1987 23 1 1 CD cord-014597-66vd2mdu 1987 24 ) ) -RRB- cord-014597-66vd2mdu 1987 25 . . . cord-014597-66vd2mdu 1988 1 Middle middle JJ cord-014597-66vd2mdu 1988 2 , , , cord-014597-66vd2mdu 1988 3 but but CC cord-014597-66vd2mdu 1988 4 also also RB cord-014597-66vd2mdu 1988 5 high high JJ cord-014597-66vd2mdu 1988 6 arm arm NN cord-014597-66vd2mdu 1988 7 density density NN cord-014597-66vd2mdu 1988 8 nano nano NN cord-014597-66vd2mdu 1988 9 - - HYPH cord-014597-66vd2mdu 1988 10 stars star NNS cord-014597-66vd2mdu 1988 11 formed form VBD cord-014597-66vd2mdu 1988 12 smaller small JJR cord-014597-66vd2mdu 1988 13 polyplexes polyplexe NNS cord-014597-66vd2mdu 1988 14 with with IN cord-014597-66vd2mdu 1988 15 hydrodynamic hydrodynamic JJ cord-014597-66vd2mdu 1988 16 radii radius NNS cord-014597-66vd2mdu 1988 17 ≤ ≤ NNP cord-014597-66vd2mdu 1988 18 300 300 CD cord-014597-66vd2mdu 1988 19 nm nm NN cord-014597-66vd2mdu 1988 20 , , , cord-014597-66vd2mdu 1988 21 a a DT cord-014597-66vd2mdu 1988 22 size size NN cord-014597-66vd2mdu 1988 23 that that WDT cord-014597-66vd2mdu 1988 24 is be VBZ cord-014597-66vd2mdu 1988 25 considered consider VBN cord-014597-66vd2mdu 1988 26 suitable suitable JJ cord-014597-66vd2mdu 1988 27 for for IN cord-014597-66vd2mdu 1988 28 endocytosis endocytosis NN cord-014597-66vd2mdu 1988 29 and and CC cord-014597-66vd2mdu 1988 30 transfection transfection NN cord-014597-66vd2mdu 1988 31 . . . cord-014597-66vd2mdu 1989 1 Transfection transfection NN cord-014597-66vd2mdu 1989 2 efficiencies efficiency NNS cord-014597-66vd2mdu 1989 3 and and CC cord-014597-66vd2mdu 1989 4 cytotoxicities cytotoxicity NNS cord-014597-66vd2mdu 1989 5 varied vary VBN cord-014597-66vd2mdu 1989 6 systematically systematically RB cord-014597-66vd2mdu 1989 7 with with IN cord-014597-66vd2mdu 1989 8 the the DT cord-014597-66vd2mdu 1989 9 nano nano NN cord-014597-66vd2mdu 1989 10 - - HYPH cord-014597-66vd2mdu 1989 11 stars star NNS cord-014597-66vd2mdu 1989 12 architecture architecture NN cord-014597-66vd2mdu 1989 13 , , , cord-014597-66vd2mdu 1989 14 with with IN cord-014597-66vd2mdu 1989 15 viability viability NN cord-014597-66vd2mdu 1989 16 showing show VBG cord-014597-66vd2mdu 1989 17 a a DT cord-014597-66vd2mdu 1989 18 more more RBR cord-014597-66vd2mdu 1989 19 pronounced pronounced JJ cord-014597-66vd2mdu 1989 20 dependency dependency NN cord-014597-66vd2mdu 1989 21 on on IN cord-014597-66vd2mdu 1989 22 the the DT cord-014597-66vd2mdu 1989 23 characteristics characteristic NNS cord-014597-66vd2mdu 1989 24 of of IN cord-014597-66vd2mdu 1989 25 the the DT cord-014597-66vd2mdu 1989 26 transfection transfection NN cord-014597-66vd2mdu 1989 27 agent agent NN cord-014597-66vd2mdu 1989 28 than than IN cord-014597-66vd2mdu 1989 29 the the DT cord-014597-66vd2mdu 1989 30 transfection transfection NN cord-014597-66vd2mdu 1989 31 efficiency efficiency NN cord-014597-66vd2mdu 1989 32 itself -PRON- PRP cord-014597-66vd2mdu 1989 33 . . . cord-014597-66vd2mdu 1990 1 The the DT cord-014597-66vd2mdu 1990 2 arm arm NN cord-014597-66vd2mdu 1990 3 density density NN cord-014597-66vd2mdu 1990 4 was be VBD cord-014597-66vd2mdu 1990 5 particularly particularly RB cord-014597-66vd2mdu 1990 6 important important JJ cord-014597-66vd2mdu 1990 7 , , , cord-014597-66vd2mdu 1990 8 with with IN cord-014597-66vd2mdu 1990 9 values value NNS cord-014597-66vd2mdu 1990 10 of of IN cord-014597-66vd2mdu 1990 11 approximately approximately RB cord-014597-66vd2mdu 1990 12 0.06 0.06 CD cord-014597-66vd2mdu 1990 13 arms/ arms/ CD cord-014597-66vd2mdu 1990 14 nm nm NN cord-014597-66vd2mdu 1990 15 2 2 CD cord-014597-66vd2mdu 1990 16 yielding yield VBG cord-014597-66vd2mdu 1990 17 the the DT cord-014597-66vd2mdu 1990 18 best good JJS cord-014597-66vd2mdu 1990 19 results result NNS cord-014597-66vd2mdu 1990 20 ( ( -LRB- cord-014597-66vd2mdu 1990 21 Fig fig NN cord-014597-66vd2mdu 1990 22 . . . cord-014597-66vd2mdu 1990 23 1a 1a CD cord-014597-66vd2mdu 1990 24 ) ) -RRB- cord-014597-66vd2mdu 1990 25 . . . cord-014597-66vd2mdu 1991 1 The the DT cord-014597-66vd2mdu 1991 2 end end NN cord-014597-66vd2mdu 1991 3 - - HYPH cord-014597-66vd2mdu 1991 4 capping cap VBG cord-014597-66vd2mdu 1991 5 the the DT cord-014597-66vd2mdu 1991 6 polycation polycation NN cord-014597-66vd2mdu 1991 7 arms arm NNS cord-014597-66vd2mdu 1991 8 with with IN cord-014597-66vd2mdu 1991 9 PDEGMA PDEGMA NNP cord-014597-66vd2mdu 1991 10 significantly significantly RB cord-014597-66vd2mdu 1991 11 improved improve VBD cord-014597-66vd2mdu 1991 12 the the DT cord-014597-66vd2mdu 1991 13 serum serum NN cord-014597-66vd2mdu 1991 14 compatibility compatibility NN cord-014597-66vd2mdu 1991 15 ( ( -LRB- cord-014597-66vd2mdu 1991 16 Fig fig NN cord-014597-66vd2mdu 1991 17 . . . cord-014597-66vd2mdu 1991 18 1b 1b CD cord-014597-66vd2mdu 1991 19 ) ) -RRB- cord-014597-66vd2mdu 1991 20 . . . cord-014597-66vd2mdu 1992 1 The the DT cord-014597-66vd2mdu 1992 2 gene gene NN cord-014597-66vd2mdu 1992 3 delivery delivery NN cord-014597-66vd2mdu 1992 4 potential potential NN cord-014597-66vd2mdu 1992 5 of of IN cord-014597-66vd2mdu 1992 6 a a DT cord-014597-66vd2mdu 1992 7 given give VBN cord-014597-66vd2mdu 1992 8 nano nano NN cord-014597-66vd2mdu 1992 9 - - HYPH cord-014597-66vd2mdu 1992 10 star star NN cord-014597-66vd2mdu 1992 11 and and CC cord-014597-66vd2mdu 1992 12 its -PRON- PRP$ cord-014597-66vd2mdu 1992 13 ability ability NN cord-014597-66vd2mdu 1992 14 to to TO cord-014597-66vd2mdu 1992 15 render render VB cord-014597-66vd2mdu 1992 16 the the DT cord-014597-66vd2mdu 1992 17 cells cell NNS cord-014597-66vd2mdu 1992 18 magnetic magnetic JJ cord-014597-66vd2mdu 1992 19 did do VBD cord-014597-66vd2mdu 1992 20 not not RB cord-014597-66vd2mdu 1992 21 correlate correlate VB cord-014597-66vd2mdu 1992 22 . . . cord-014597-66vd2mdu 1993 1 Although although IN cord-014597-66vd2mdu 1993 2 , , , cord-014597-66vd2mdu 1993 3 compared compare VBN cord-014597-66vd2mdu 1993 4 to to IN cord-014597-66vd2mdu 1993 5 the the DT cord-014597-66vd2mdu 1993 6 non non JJ cord-014597-66vd2mdu 1993 7 - - JJ cord-014597-66vd2mdu 1993 8 separated separated JJ cord-014597-66vd2mdu 1993 9 cells cell NNS cord-014597-66vd2mdu 1993 10 , , , cord-014597-66vd2mdu 1993 11 EGFP EGFP NNP cord-014597-66vd2mdu 1993 12 - - HYPH cord-014597-66vd2mdu 1993 13 expressing express VBG cord-014597-66vd2mdu 1993 14 cells cell NNS cord-014597-66vd2mdu 1993 15 were be VBD cord-014597-66vd2mdu 1993 16 consistently consistently RB cord-014597-66vd2mdu 1993 17 more more RBR cord-014597-66vd2mdu 1993 18 frequent frequent JJ cord-014597-66vd2mdu 1993 19 in in IN cord-014597-66vd2mdu 1993 20 the the DT cord-014597-66vd2mdu 1993 21 magnetic magnetic JJ cord-014597-66vd2mdu 1993 22 cell cell NN cord-014597-66vd2mdu 1993 23 fraction fraction NN cord-014597-66vd2mdu 1993 24 , , , cord-014597-66vd2mdu 1993 25 while while IN cord-014597-66vd2mdu 1993 26 the the DT cord-014597-66vd2mdu 1993 27 non non JJ cord-014597-66vd2mdu 1993 28 - - JJ cord-014597-66vd2mdu 1993 29 magnetic magnetic JJ cord-014597-66vd2mdu 1993 30 fraction fraction NN cord-014597-66vd2mdu 1993 31 was be VBD cord-014597-66vd2mdu 1993 32 slightly slightly RB cord-014597-66vd2mdu 1993 33 depleted deplete VBN cord-014597-66vd2mdu 1993 34 . . . cord-014597-66vd2mdu 1994 1 When when WRB cord-014597-66vd2mdu 1994 2 the the DT cord-014597-66vd2mdu 1994 3 EGFP EGFP NNP cord-014597-66vd2mdu 1994 4 - - HYPH cord-014597-66vd2mdu 1994 5 expressing express VBG cord-014597-66vd2mdu 1994 6 cells cell NNS cord-014597-66vd2mdu 1994 7 were be VBD cord-014597-66vd2mdu 1994 8 further further RB cord-014597-66vd2mdu 1994 9 divided divide VBN cord-014597-66vd2mdu 1994 10 into into IN cord-014597-66vd2mdu 1994 11 low low JJ cord-014597-66vd2mdu 1994 12 , , , cord-014597-66vd2mdu 1994 13 middle middle JJ cord-014597-66vd2mdu 1994 14 and and CC cord-014597-66vd2mdu 1994 15 high high JJ cord-014597-66vd2mdu 1994 16 producers producer NNS cord-014597-66vd2mdu 1994 17 , , , cord-014597-66vd2mdu 1994 18 a a DT cord-014597-66vd2mdu 1994 19 statistically statistically RB cord-014597-66vd2mdu 1994 20 significant significant JJ cord-014597-66vd2mdu 1994 21 shift shift NN cord-014597-66vd2mdu 1994 22 towards towards IN cord-014597-66vd2mdu 1994 23 the the DT cord-014597-66vd2mdu 1994 24 high high JJ cord-014597-66vd2mdu 1994 25 producers producer NNS cord-014597-66vd2mdu 1994 26 was be VBD cord-014597-66vd2mdu 1994 27 observed observe VBN cord-014597-66vd2mdu 1994 28 in in IN cord-014597-66vd2mdu 1994 29 the the DT cord-014597-66vd2mdu 1994 30 magnetic magnetic JJ cord-014597-66vd2mdu 1994 31 cell cell NN cord-014597-66vd2mdu 1994 32 fraction fraction NN cord-014597-66vd2mdu 1994 33 ( ( -LRB- cord-014597-66vd2mdu 1994 34 Fig Fig NNP cord-014597-66vd2mdu 1994 35 . . . cord-014597-66vd2mdu 1994 36 1c 1c CD cord-014597-66vd2mdu 1994 37 ) ) -RRB- cord-014597-66vd2mdu 1994 38 . . . cord-014597-66vd2mdu 1995 1 A a DT cord-014597-66vd2mdu 1995 2 nonparametric nonparametric JJ cord-014597-66vd2mdu 1995 3 Spearman Spearman NNP cord-014597-66vd2mdu 1995 4 correlation correlation NN cord-014597-66vd2mdu 1995 5 analysis analysis NN cord-014597-66vd2mdu 1995 6 was be VBD cord-014597-66vd2mdu 1995 7 used use VBN cord-014597-66vd2mdu 1995 8 to to TO cord-014597-66vd2mdu 1995 9 statistically statistically RB cord-014597-66vd2mdu 1995 10 evaluate evaluate VB cord-014597-66vd2mdu 1995 11 possible possible JJ cord-014597-66vd2mdu 1995 12 links link NNS cord-014597-66vd2mdu 1995 13 between between IN cord-014597-66vd2mdu 1995 14 the the DT cord-014597-66vd2mdu 1995 15 molecular molecular JJ cord-014597-66vd2mdu 1995 16 characteristics characteristic NNS cord-014597-66vd2mdu 1995 17 of of IN cord-014597-66vd2mdu 1995 18 the the DT cord-014597-66vd2mdu 1995 19 nano nano NN cord-014597-66vd2mdu 1995 20 - - HYPH cord-014597-66vd2mdu 1995 21 stars star NNS cord-014597-66vd2mdu 1995 22 , , , cord-014597-66vd2mdu 1995 23 the the DT cord-014597-66vd2mdu 1995 24 physicochemical physicochemical JJ cord-014597-66vd2mdu 1995 25 properties property NNS cord-014597-66vd2mdu 1995 26 of of IN cord-014597-66vd2mdu 1995 27 the the DT cord-014597-66vd2mdu 1995 28 corresponding correspond VBG cord-014597-66vd2mdu 1995 29 polyplexes polyplexe NNS cord-014597-66vd2mdu 1995 30 , , , cord-014597-66vd2mdu 1995 31 the the DT cord-014597-66vd2mdu 1995 32 transfection transfection NN cord-014597-66vd2mdu 1995 33 conditions condition NNS cord-014597-66vd2mdu 1995 34 , , , cord-014597-66vd2mdu 1995 35 and and CC cord-014597-66vd2mdu 1995 36 the the DT cord-014597-66vd2mdu 1995 37 cellular cellular JJ cord-014597-66vd2mdu 1995 38 reactions reaction NNS cord-014597-66vd2mdu 1995 39 . . . cord-014597-66vd2mdu 1996 1 The the DT cord-014597-66vd2mdu 1996 2 resulting result VBG cord-014597-66vd2mdu 1996 3 correlogram correlogram NN cord-014597-66vd2mdu 1996 4 is be VBZ cord-014597-66vd2mdu 1996 5 shown show VBN cord-014597-66vd2mdu 1996 6 in in IN cord-014597-66vd2mdu 1996 7 Fig Fig NNP cord-014597-66vd2mdu 1996 8 . . . cord-014597-66vd2mdu 1997 1 1d 1d NNP cord-014597-66vd2mdu 1997 2 . . . cord-014597-66vd2mdu 1998 1 Transfection transfection NN cord-014597-66vd2mdu 1998 2 agents agent NNS cord-014597-66vd2mdu 1998 3 with with IN cord-014597-66vd2mdu 1998 4 magnetic magnetic JJ cord-014597-66vd2mdu 1998 5 properties property NNS cord-014597-66vd2mdu 1998 6 enlarge enlarge VBP cord-014597-66vd2mdu 1998 7 the the DT cord-014597-66vd2mdu 1998 8 toolbox toolbox NN cord-014597-66vd2mdu 1998 9 for for IN cord-014597-66vd2mdu 1998 10 studying study VBG cord-014597-66vd2mdu 1998 11 non non JJ cord-014597-66vd2mdu 1998 12 - - JJ cord-014597-66vd2mdu 1998 13 viral viral JJ cord-014597-66vd2mdu 1998 14 gene gene NN cord-014597-66vd2mdu 1998 15 delivery delivery NN cord-014597-66vd2mdu 1998 16 , , , cord-014597-66vd2mdu 1998 17 since since IN cord-014597-66vd2mdu 1998 18 cellular cellular JJ cord-014597-66vd2mdu 1998 19 magnetism magnetism NN cord-014597-66vd2mdu 1998 20 is be VBZ cord-014597-66vd2mdu 1998 21 added add VBN cord-014597-66vd2mdu 1998 22 as as IN cord-014597-66vd2mdu 1998 23 a a DT cord-014597-66vd2mdu 1998 24 new new JJ cord-014597-66vd2mdu 1998 25 parameter parameter NN cord-014597-66vd2mdu 1998 26 . . . cord-014597-66vd2mdu 1999 1 This this DT cord-014597-66vd2mdu 1999 2 allows allow VBZ cord-014597-66vd2mdu 1999 3 , , , cord-014597-66vd2mdu 1999 4 inter inter NNP cord-014597-66vd2mdu 1999 5 alia alia NNP cord-014597-66vd2mdu 1999 6 , , , cord-014597-66vd2mdu 1999 7 a a DT cord-014597-66vd2mdu 1999 8 distinction distinction NN cord-014597-66vd2mdu 1999 9 between between IN cord-014597-66vd2mdu 1999 10 mere mere JJ cord-014597-66vd2mdu 1999 11 cellular cellular JJ cord-014597-66vd2mdu 1999 12 interaction interaction NN cord-014597-66vd2mdu 1999 13 and and CC cord-014597-66vd2mdu 1999 14 actual actual JJ cord-014597-66vd2mdu 1999 15 uptake uptake NN cord-014597-66vd2mdu 1999 16 , , , cord-014597-66vd2mdu 1999 17 which which WDT cord-014597-66vd2mdu 1999 18 is be VBZ cord-014597-66vd2mdu 1999 19 otherwise otherwise RB cord-014597-66vd2mdu 1999 20 difficult difficult JJ cord-014597-66vd2mdu 1999 21 . . . cord-014597-66vd2mdu 2000 1 Viability viability NN cord-014597-66vd2mdu 2000 2 showed show VBD cord-014597-66vd2mdu 2000 3 a a DT cord-014597-66vd2mdu 2000 4 much much RB cord-014597-66vd2mdu 2000 5 more more RBR cord-014597-66vd2mdu 2000 6 pronounced pronounced JJ cord-014597-66vd2mdu 2000 7 dependency dependency NN cord-014597-66vd2mdu 2000 8 on on IN cord-014597-66vd2mdu 2000 9 the the DT cord-014597-66vd2mdu 2000 10 characteristics characteristic NNS cord-014597-66vd2mdu 2000 11 of of IN cord-014597-66vd2mdu 2000 12 the the DT cord-014597-66vd2mdu 2000 13 transfection transfection NN cord-014597-66vd2mdu 2000 14 agent agent NN cord-014597-66vd2mdu 2000 15 / / SYM cord-014597-66vd2mdu 2000 16 polyplex polyplex NN cord-014597-66vd2mdu 2000 17 than than IN cord-014597-66vd2mdu 2000 18 the the DT cord-014597-66vd2mdu 2000 19 transfection transfection NN cord-014597-66vd2mdu 2000 20 efficiency efficiency NN cord-014597-66vd2mdu 2000 21 itself -PRON- PRP cord-014597-66vd2mdu 2000 22 , , , cord-014597-66vd2mdu 2000 23 which which WDT cord-014597-66vd2mdu 2000 24 should should MD cord-014597-66vd2mdu 2000 25 be be VB cord-014597-66vd2mdu 2000 26 taken take VBN cord-014597-66vd2mdu 2000 27 into into IN cord-014597-66vd2mdu 2000 28 account account NN cord-014597-66vd2mdu 2000 29 during during IN cord-014597-66vd2mdu 2000 30 method method NN cord-014597-66vd2mdu 2000 31 optimization optimization NN cord-014597-66vd2mdu 2000 32 . . . cord-014597-66vd2mdu 2001 1 End end NN cord-014597-66vd2mdu 2001 2 - - HYPH cord-014597-66vd2mdu 2001 3 capping cap VBG cord-014597-66vd2mdu 2001 4 the the DT cord-014597-66vd2mdu 2001 5 polycationic polycationic NNP cord-014597-66vd2mdu 2001 6 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 2001 7 - - HYPH cord-014597-66vd2mdu 2001 8 arms arm NNS cord-014597-66vd2mdu 2001 9 with with IN cord-014597-66vd2mdu 2001 10 PDEGMA PDEGMA NNP cord-014597-66vd2mdu 2001 11 - - HYPH cord-014597-66vd2mdu 2001 12 blocks block NNS cord-014597-66vd2mdu 2001 13 improved improve VBD cord-014597-66vd2mdu 2001 14 the the DT cord-014597-66vd2mdu 2001 15 compatibility compatibility NN cord-014597-66vd2mdu 2001 16 of of IN cord-014597-66vd2mdu 2001 17 the the DT cord-014597-66vd2mdu 2001 18 polycationic polycationic NNP cord-014597-66vd2mdu 2001 19 nano nano NNP cord-014597-66vd2mdu 2001 20 - - HYPH cord-014597-66vd2mdu 2001 21 stars star NNS cord-014597-66vd2mdu 2001 22 with with IN cord-014597-66vd2mdu 2001 23 serum serum NN cord-014597-66vd2mdu 2001 24 components component NNS cord-014597-66vd2mdu 2001 25 . . . cord-014597-66vd2mdu 2002 1 In in IN cord-014597-66vd2mdu 2002 2 future future NN cord-014597-66vd2mdu 2002 3 optimized optimize VBN cord-014597-66vd2mdu 2002 4 , , , cord-014597-66vd2mdu 2002 5 blood blood NN cord-014597-66vd2mdu 2002 6 - - HYPH cord-014597-66vd2mdu 2002 7 compatible compatible JJ cord-014597-66vd2mdu 2002 8 , , , cord-014597-66vd2mdu 2002 9 nano nano NN cord-014597-66vd2mdu 2002 10 - - HYPH cord-014597-66vd2mdu 2002 11 stars star NNS cord-014597-66vd2mdu 2002 12 , , , cord-014597-66vd2mdu 2002 13 which which WDT cord-014597-66vd2mdu 2002 14 can can MD cord-014597-66vd2mdu 2002 15 be be VB cord-014597-66vd2mdu 2002 16 retained retain VBN cord-014597-66vd2mdu 2002 17 / / SYM cord-014597-66vd2mdu 2002 18 directed direct VBN cord-014597-66vd2mdu 2002 19 by by IN cord-014597-66vd2mdu 2002 20 magnetic magnetic JJ cord-014597-66vd2mdu 2002 21 fields field NNS cord-014597-66vd2mdu 2002 22 , , , cord-014597-66vd2mdu 2002 23 could could MD cord-014597-66vd2mdu 2002 24 become become VB cord-014597-66vd2mdu 2002 25 options option NNS cord-014597-66vd2mdu 2002 26 for for IN cord-014597-66vd2mdu 2002 27 non non JJ cord-014597-66vd2mdu 2002 28 - - JJ cord-014597-66vd2mdu 2002 29 viral viral JJ cord-014597-66vd2mdu 2002 30 gene gene NN cord-014597-66vd2mdu 2002 31 delivery delivery NN cord-014597-66vd2mdu 2002 32 in in IN cord-014597-66vd2mdu 2002 33 vivo vivo NNP cord-014597-66vd2mdu 2002 34 . . . cord-014597-66vd2mdu 2003 1 The the DT cord-014597-66vd2mdu 2003 2 increasing increase VBG cord-014597-66vd2mdu 2003 3 demand demand NN cord-014597-66vd2mdu 2003 4 for for IN cord-014597-66vd2mdu 2003 5 monoclonal monoclonal JJ cord-014597-66vd2mdu 2003 6 antibodies antibody NNS cord-014597-66vd2mdu 2003 7 has have VBZ cord-014597-66vd2mdu 2003 8 necessitated necessitate VBN cord-014597-66vd2mdu 2003 9 the the DT cord-014597-66vd2mdu 2003 10 need need NN cord-014597-66vd2mdu 2003 11 to to TO cord-014597-66vd2mdu 2003 12 increase increase VB cord-014597-66vd2mdu 2003 13 the the DT cord-014597-66vd2mdu 2003 14 productivity productivity NN cord-014597-66vd2mdu 2003 15 of of IN cord-014597-66vd2mdu 2003 16 current current JJ cord-014597-66vd2mdu 2003 17 industrial industrial JJ cord-014597-66vd2mdu 2003 18 cell cell NN cord-014597-66vd2mdu 2003 19 lines line NNS cord-014597-66vd2mdu 2003 20 . . . cord-014597-66vd2mdu 2004 1 In in IN cord-014597-66vd2mdu 2004 2 our -PRON- PRP$ cord-014597-66vd2mdu 2004 3 earlier early JJR cord-014597-66vd2mdu 2004 4 study study NN cord-014597-66vd2mdu 2004 5 [ [ -LRB- cord-014597-66vd2mdu 2004 6 1 1 CD cord-014597-66vd2mdu 2004 7 ] ] -RRB- cord-014597-66vd2mdu 2004 8 , , , cord-014597-66vd2mdu 2004 9 we -PRON- PRP cord-014597-66vd2mdu 2004 10 had have VBD cord-014597-66vd2mdu 2004 11 shown show VBN cord-014597-66vd2mdu 2004 12 that that DT cord-014597-66vd2mdu 2004 13 treatment treatment NN cord-014597-66vd2mdu 2004 14 with with IN cord-014597-66vd2mdu 2004 15 ER er NN cord-014597-66vd2mdu 2004 16 - - HYPH cord-014597-66vd2mdu 2004 17 stress stress NN cord-014597-66vd2mdu 2004 18 inducer inducer NN cord-014597-66vd2mdu 2004 19 , , , cord-014597-66vd2mdu 2004 20 Tunicamycin Tunicamycin NNP cord-014597-66vd2mdu 2004 21 significantly significantly RB cord-014597-66vd2mdu 2004 22 increased increase VBD cord-014597-66vd2mdu 2004 23 the the DT cord-014597-66vd2mdu 2004 24 titers titer NNS cord-014597-66vd2mdu 2004 25 and and CC cord-014597-66vd2mdu 2004 26 productivity productivity NN cord-014597-66vd2mdu 2004 27 in in IN cord-014597-66vd2mdu 2004 28 recombinant recombinant JJ cord-014597-66vd2mdu 2004 29 CHO CHO NNP cord-014597-66vd2mdu 2004 30 cell cell NN cord-014597-66vd2mdu 2004 31 lines line NNS cord-014597-66vd2mdu 2004 32 with with IN cord-014597-66vd2mdu 2004 33 a a DT cord-014597-66vd2mdu 2004 34 simultaneous simultaneous JJ cord-014597-66vd2mdu 2004 35 upregulation upregulation NN cord-014597-66vd2mdu 2004 36 of of IN cord-014597-66vd2mdu 2004 37 many many JJ cord-014597-66vd2mdu 2004 38 genes gene NNS cord-014597-66vd2mdu 2004 39 from from IN cord-014597-66vd2mdu 2004 40 the the DT cord-014597-66vd2mdu 2004 41 unfolded unfolded JJ cord-014597-66vd2mdu 2004 42 protein protein NN cord-014597-66vd2mdu 2004 43 response response NN cord-014597-66vd2mdu 2004 44 pathway pathway NN cord-014597-66vd2mdu 2004 45 ( ( -LRB- cord-014597-66vd2mdu 2004 46 UPR UPR NNP cord-014597-66vd2mdu 2004 47 ) ) -RRB- cord-014597-66vd2mdu 2004 48 . . . cord-014597-66vd2mdu 2005 1 However however RB cord-014597-66vd2mdu 2005 2 the the DT cord-014597-66vd2mdu 2005 3 loss loss NN cord-014597-66vd2mdu 2005 4 in in IN cord-014597-66vd2mdu 2005 5 cell cell NN cord-014597-66vd2mdu 2005 6 viability viability NN cord-014597-66vd2mdu 2005 7 prevented prevent VBD cord-014597-66vd2mdu 2005 8 a a DT cord-014597-66vd2mdu 2005 9 sustained sustained JJ cord-014597-66vd2mdu 2005 10 increase increase NN cord-014597-66vd2mdu 2005 11 in in IN cord-014597-66vd2mdu 2005 12 titers titer NNS cord-014597-66vd2mdu 2005 13 . . . cord-014597-66vd2mdu 2006 1 In in IN cord-014597-66vd2mdu 2006 2 the the DT cord-014597-66vd2mdu 2006 3 current current JJ cord-014597-66vd2mdu 2006 4 study study NN cord-014597-66vd2mdu 2006 5 we -PRON- PRP cord-014597-66vd2mdu 2006 6 explore explore VBP cord-014597-66vd2mdu 2006 7 the the DT cord-014597-66vd2mdu 2006 8 effect effect NN cord-014597-66vd2mdu 2006 9 of of IN cord-014597-66vd2mdu 2006 10 varying vary VBG cord-014597-66vd2mdu 2006 11 concentrations concentration NNS cord-014597-66vd2mdu 2006 12 of of IN cord-014597-66vd2mdu 2006 13 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2006 14 and and CC cord-014597-66vd2mdu 2006 15 treatment treatment NN cord-014597-66vd2mdu 2006 16 times time NNS cord-014597-66vd2mdu 2006 17 , , , cord-014597-66vd2mdu 2006 18 such such JJ cord-014597-66vd2mdu 2006 19 as as IN cord-014597-66vd2mdu 2006 20 to to TO cord-014597-66vd2mdu 2006 21 modulate modulate VB cord-014597-66vd2mdu 2006 22 the the DT cord-014597-66vd2mdu 2006 23 increase increase NN cord-014597-66vd2mdu 2006 24 in in IN cord-014597-66vd2mdu 2006 25 protein protein NN cord-014597-66vd2mdu 2006 26 folding folding NN cord-014597-66vd2mdu 2006 27 capacity capacity NN cord-014597-66vd2mdu 2006 28 while while IN cord-014597-66vd2mdu 2006 29 preventing prevent VBG cord-014597-66vd2mdu 2006 30 induction induction NN cord-014597-66vd2mdu 2006 31 of of IN cord-014597-66vd2mdu 2006 32 apoptosis apoptosis NN cord-014597-66vd2mdu 2006 33 . . . cord-014597-66vd2mdu 2007 1 Anti anti JJ cord-014597-66vd2mdu 2007 2 - - JJ cord-014597-66vd2mdu 2007 3 rhesus rhesus JJ cord-014597-66vd2mdu 2007 4 IgG igg NN cord-014597-66vd2mdu 2007 5 - - HYPH cord-014597-66vd2mdu 2007 6 secreting secrete VBG cord-014597-66vd2mdu 2007 7 CHO CHO NNP cord-014597-66vd2mdu 2007 8 cells cell NNS cord-014597-66vd2mdu 2007 9 [ [ -LRB- cord-014597-66vd2mdu 2007 10 2 2 CD cord-014597-66vd2mdu 2007 11 ] ] -RRB- cord-014597-66vd2mdu 2007 12 were be VBD cord-014597-66vd2mdu 2007 13 cultured culture VBN cord-014597-66vd2mdu 2007 14 in in IN cord-014597-66vd2mdu 2007 15 SF SF NNP cord-014597-66vd2mdu 2007 16 - - HYPH cord-014597-66vd2mdu 2007 17 CDM CDM NNP cord-014597-66vd2mdu 2007 18 in in IN cord-014597-66vd2mdu 2007 19 125 125 CD cord-014597-66vd2mdu 2007 20 mL ml NN cord-014597-66vd2mdu 2007 21 shake shake NN cord-014597-66vd2mdu 2007 22 flasks flask NNS cord-014597-66vd2mdu 2007 23 . . . cord-014597-66vd2mdu 2008 1 The the DT cord-014597-66vd2mdu 2008 2 cells cell NNS cord-014597-66vd2mdu 2008 3 were be VBD cord-014597-66vd2mdu 2008 4 treated treat VBN cord-014597-66vd2mdu 2008 5 with with IN cord-014597-66vd2mdu 2008 6 varying vary VBG cord-014597-66vd2mdu 2008 7 concentrations concentration NNS cord-014597-66vd2mdu 2008 8 ( ( -LRB- cord-014597-66vd2mdu 2008 9 30 30 CD cord-014597-66vd2mdu 2008 10 - - SYM cord-014597-66vd2mdu 2008 11 500 500 CD cord-014597-66vd2mdu 2008 12 ng ng NN cord-014597-66vd2mdu 2008 13 / / SYM cord-014597-66vd2mdu 2008 14 mL ml NN cord-014597-66vd2mdu 2008 15 ) ) -RRB- cord-014597-66vd2mdu 2008 16 of of IN cord-014597-66vd2mdu 2008 17 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2008 18 in in IN cord-014597-66vd2mdu 2008 19 a a DT cord-014597-66vd2mdu 2008 20 batch batch NN cord-014597-66vd2mdu 2008 21 culture culture NN cord-014597-66vd2mdu 2008 22 . . . cord-014597-66vd2mdu 2009 1 Further further RB cord-014597-66vd2mdu 2009 2 , , , cord-014597-66vd2mdu 2009 3 the the DT cord-014597-66vd2mdu 2009 4 effect effect NN cord-014597-66vd2mdu 2009 5 of of IN cord-014597-66vd2mdu 2009 6 treatment treatment NN cord-014597-66vd2mdu 2009 7 with with IN cord-014597-66vd2mdu 2009 8 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2009 9 for for IN cord-014597-66vd2mdu 2009 10 short short JJ cord-014597-66vd2mdu 2009 11 periods period NNS cord-014597-66vd2mdu 2009 12 of of IN cord-014597-66vd2mdu 2009 13 time time NN cord-014597-66vd2mdu 2009 14 ( ( -LRB- cord-014597-66vd2mdu 2009 15 24 24 CD cord-014597-66vd2mdu 2009 16 hrs hrs NN cord-014597-66vd2mdu 2009 17 ) ) -RRB- cord-014597-66vd2mdu 2009 18 was be VBD cord-014597-66vd2mdu 2009 19 also also RB cord-014597-66vd2mdu 2009 20 evaluated evaluate VBN cord-014597-66vd2mdu 2009 21 . . . cord-014597-66vd2mdu 2010 1 IgG IgG NNP cord-014597-66vd2mdu 2010 2 titers titers NNP cord-014597-66vd2mdu 2010 3 and and CC cord-014597-66vd2mdu 2010 4 mRNA mRNA NNP cord-014597-66vd2mdu 2010 5 expression expression NN cord-014597-66vd2mdu 2010 6 levels level NNS cord-014597-66vd2mdu 2010 7 were be VBD cord-014597-66vd2mdu 2010 8 quantified quantify VBN cord-014597-66vd2mdu 2010 9 using use VBG cord-014597-66vd2mdu 2010 10 ELISA ELISA NNP cord-014597-66vd2mdu 2010 11 and and CC cord-014597-66vd2mdu 2010 12 qRT qRT NNP cord-014597-66vd2mdu 2010 13 - - HYPH cord-014597-66vd2mdu 2010 14 PCR PCR NNP cord-014597-66vd2mdu 2010 15 ( ( -LRB- cord-014597-66vd2mdu 2010 16 Illumina Illumina NNP cord-014597-66vd2mdu 2010 17 ) ) -RRB- cord-014597-66vd2mdu 2010 18 , , , cord-014597-66vd2mdu 2010 19 respectively respectively RB cord-014597-66vd2mdu 2010 20 . . . cord-014597-66vd2mdu 2011 1 Results result NNS cord-014597-66vd2mdu 2011 2 CHO CHO NNP cord-014597-66vd2mdu 2011 3 cells cell NNS cord-014597-66vd2mdu 2011 4 were be VBD cord-014597-66vd2mdu 2011 5 treated treat VBN cord-014597-66vd2mdu 2011 6 with with IN cord-014597-66vd2mdu 2011 7 different different JJ cord-014597-66vd2mdu 2011 8 concentrations concentration NNS cord-014597-66vd2mdu 2011 9 of of IN cord-014597-66vd2mdu 2011 10 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2011 11 and and CC cord-014597-66vd2mdu 2011 12 cultured culture VBN cord-014597-66vd2mdu 2011 13 in in IN cord-014597-66vd2mdu 2011 14 a a DT cord-014597-66vd2mdu 2011 15 batch batch NN cord-014597-66vd2mdu 2011 16 for for IN cord-014597-66vd2mdu 2011 17 8 8 CD cord-014597-66vd2mdu 2011 18 days day NNS cord-014597-66vd2mdu 2011 19 ( ( -LRB- cord-014597-66vd2mdu 2011 20 referred refer VBN cord-014597-66vd2mdu 2011 21 as as IN cord-014597-66vd2mdu 2011 22 Continuous continuous JJ cord-014597-66vd2mdu 2011 23 treatment treatment NN cord-014597-66vd2mdu 2011 24 / / SYM cord-014597-66vd2mdu 2011 25 CTE CTE NNP cord-014597-66vd2mdu 2011 26 ) ) -RRB- cord-014597-66vd2mdu 2011 27 . . . cord-014597-66vd2mdu 2012 1 Figure figure NN cord-014597-66vd2mdu 2012 2 1a 1a CD cord-014597-66vd2mdu 2012 3 presents present VBZ cord-014597-66vd2mdu 2012 4 the the DT cord-014597-66vd2mdu 2012 5 maximum maximum JJ cord-014597-66vd2mdu 2012 6 VCD vcd NN cord-014597-66vd2mdu 2012 7 and and CC cord-014597-66vd2mdu 2012 8 % % NN cord-014597-66vd2mdu 2012 9 drop drop NN cord-014597-66vd2mdu 2012 10 in in IN cord-014597-66vd2mdu 2012 11 viability viability NN cord-014597-66vd2mdu 2012 12 under under IN cord-014597-66vd2mdu 2012 13 treatment treatment NN cord-014597-66vd2mdu 2012 14 . . . cord-014597-66vd2mdu 2013 1 A a DT cord-014597-66vd2mdu 2013 2 dose dose NN cord-014597-66vd2mdu 2013 3 - - HYPH cord-014597-66vd2mdu 2013 4 dependent dependent JJ cord-014597-66vd2mdu 2013 5 inhibitory inhibitory JJ cord-014597-66vd2mdu 2013 6 effect effect NN cord-014597-66vd2mdu 2013 7 is be VBZ cord-014597-66vd2mdu 2013 8 observed observe VBN cord-014597-66vd2mdu 2013 9 on on IN cord-014597-66vd2mdu 2013 10 growth growth NN cord-014597-66vd2mdu 2013 11 and and CC cord-014597-66vd2mdu 2013 12 viability viability NN cord-014597-66vd2mdu 2013 13 of of IN cord-014597-66vd2mdu 2013 14 cells cell NNS cord-014597-66vd2mdu 2013 15 in in IN cord-014597-66vd2mdu 2013 16 CTE CTE NNP cord-014597-66vd2mdu 2013 17 - - HYPH cord-014597-66vd2mdu 2013 18 cultures culture NNS cord-014597-66vd2mdu 2013 19 , , , cord-014597-66vd2mdu 2013 20 with with IN cord-014597-66vd2mdu 2013 21 minimal minimal JJ cord-014597-66vd2mdu 2013 22 inhibition inhibition NN cord-014597-66vd2mdu 2013 23 as as IN cord-014597-66vd2mdu 2013 24 lower low JJR cord-014597-66vd2mdu 2013 25 concentrations concentration NNS cord-014597-66vd2mdu 2013 26 . . . cord-014597-66vd2mdu 2014 1 Contrastingly contrastingly RB cord-014597-66vd2mdu 2014 2 , , , cord-014597-66vd2mdu 2014 3 IgG igg NN cord-014597-66vd2mdu 2014 4 titers titer NNS cord-014597-66vd2mdu 2014 5 ( ( -LRB- cord-014597-66vd2mdu 2014 6 Fig Fig NNP cord-014597-66vd2mdu 2014 7 . . . cord-014597-66vd2mdu 2014 8 1b 1b LS cord-014597-66vd2mdu 2014 9 ) ) -RRB- cord-014597-66vd2mdu 2014 10 were be VBD cord-014597-66vd2mdu 2014 11 higher high JJR cord-014597-66vd2mdu 2014 12 in in IN cord-014597-66vd2mdu 2014 13 treated treat VBN cord-014597-66vd2mdu 2014 14 cultures culture NNS cord-014597-66vd2mdu 2014 15 w.r.t w.r.t JJ cord-014597-66vd2mdu 2014 16 . . . cord-014597-66vd2mdu 2014 17 control control NN cord-014597-66vd2mdu 2014 18 in in IN cord-014597-66vd2mdu 2014 19 initial initial JJ cord-014597-66vd2mdu 2014 20 phase phase NN cord-014597-66vd2mdu 2014 21 of of IN cord-014597-66vd2mdu 2014 22 the the DT cord-014597-66vd2mdu 2014 23 cultures culture NNS cord-014597-66vd2mdu 2014 24 at at IN cord-014597-66vd2mdu 2014 25 all all PDT cord-014597-66vd2mdu 2014 26 the the DT cord-014597-66vd2mdu 2014 27 concentrations concentration NNS cord-014597-66vd2mdu 2014 28 of of IN cord-014597-66vd2mdu 2014 29 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2014 30 . . . cord-014597-66vd2mdu 2015 1 The the DT cord-014597-66vd2mdu 2015 2 per per IN cord-014597-66vd2mdu 2015 3 - - HYPH cord-014597-66vd2mdu 2015 4 cell cell NN cord-014597-66vd2mdu 2015 5 productivity productivity NN cord-014597-66vd2mdu 2015 6 ( ( -LRB- cord-014597-66vd2mdu 2015 7 Fig Fig NNP cord-014597-66vd2mdu 2015 8 . . . cord-014597-66vd2mdu 2015 9 1c 1c NNP cord-014597-66vd2mdu 2015 10 ) ) -RRB- cord-014597-66vd2mdu 2015 11 also also RB cord-014597-66vd2mdu 2015 12 showed show VBD cord-014597-66vd2mdu 2015 13 a a DT cord-014597-66vd2mdu 2015 14 significant significant JJ cord-014597-66vd2mdu 2015 15 increase increase NN cord-014597-66vd2mdu 2015 16 w.r.t w.r.t JJ cord-014597-66vd2mdu 2015 17 control control NN cord-014597-66vd2mdu 2015 18 at at IN cord-014597-66vd2mdu 2015 19 all all PDT cord-014597-66vd2mdu 2015 20 the the DT cord-014597-66vd2mdu 2015 21 concentrations concentration NNS cord-014597-66vd2mdu 2015 22 of of IN cord-014597-66vd2mdu 2015 23 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2015 24 . . . cord-014597-66vd2mdu 2016 1 However however RB cord-014597-66vd2mdu 2016 2 , , , cord-014597-66vd2mdu 2016 3 the the DT cord-014597-66vd2mdu 2016 4 increased increase VBN cord-014597-66vd2mdu 2016 5 productivity productivity NN cord-014597-66vd2mdu 2016 6 due due IN cord-014597-66vd2mdu 2016 7 to to IN cord-014597-66vd2mdu 2016 8 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2016 9 was be VBD cord-014597-66vd2mdu 2016 10 not not RB cord-014597-66vd2mdu 2016 11 sustained sustain VBN cord-014597-66vd2mdu 2016 12 and and CC cord-014597-66vd2mdu 2016 13 levels level NNS cord-014597-66vd2mdu 2016 14 become become VBP cord-014597-66vd2mdu 2016 15 similar similar JJ cord-014597-66vd2mdu 2016 16 to to TO cord-014597-66vd2mdu 2016 17 control control NN cord-014597-66vd2mdu 2016 18 after after IN cord-014597-66vd2mdu 2016 19 day day NN cord-014597-66vd2mdu 2016 20 3 3 CD cord-014597-66vd2mdu 2016 21 ( ( -LRB- cord-014597-66vd2mdu 2016 22 data datum NNS cord-014597-66vd2mdu 2016 23 not not RB cord-014597-66vd2mdu 2016 24 shown show VBN cord-014597-66vd2mdu 2016 25 ) ) -RRB- cord-014597-66vd2mdu 2016 26 . . . cord-014597-66vd2mdu 2017 1 To to TO cord-014597-66vd2mdu 2017 2 prevent prevent VB cord-014597-66vd2mdu 2017 3 loss loss NN cord-014597-66vd2mdu 2017 4 of of IN cord-014597-66vd2mdu 2017 5 viability viability NN cord-014597-66vd2mdu 2017 6 due due IN cord-014597-66vd2mdu 2017 7 to to IN cord-014597-66vd2mdu 2017 8 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2017 9 , , , cord-014597-66vd2mdu 2017 10 the the DT cord-014597-66vd2mdu 2017 11 effect effect NN cord-014597-66vd2mdu 2017 12 of of IN cord-014597-66vd2mdu 2017 13 short short JJ cord-014597-66vd2mdu 2017 14 - - HYPH cord-014597-66vd2mdu 2017 15 term term NN cord-014597-66vd2mdu 2017 16 treatment treatment NN cord-014597-66vd2mdu 2017 17 ( ( -LRB- cord-014597-66vd2mdu 2017 18 STE STE NNP cord-014597-66vd2mdu 2017 19 ) ) -RRB- cord-014597-66vd2mdu 2017 20 with with IN cord-014597-66vd2mdu 2017 21 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2017 22 was be VBD cord-014597-66vd2mdu 2017 23 explored explore VBN cord-014597-66vd2mdu 2017 24 . . . cord-014597-66vd2mdu 2018 1 Cells cell NNS cord-014597-66vd2mdu 2018 2 treated treat VBN cord-014597-66vd2mdu 2018 3 with with IN cord-014597-66vd2mdu 2018 4 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2018 5 for for IN cord-014597-66vd2mdu 2018 6 24 24 CD cord-014597-66vd2mdu 2018 7 hours hour NNS cord-014597-66vd2mdu 2018 8 were be VBD cord-014597-66vd2mdu 2018 9 harvested harvest VBN cord-014597-66vd2mdu 2018 10 ( ( -LRB- cord-014597-66vd2mdu 2018 11 corresponding correspond VBG cord-014597-66vd2mdu 2018 12 to to IN cord-014597-66vd2mdu 2018 13 day day NN cord-014597-66vd2mdu 2018 14 2 2 CD cord-014597-66vd2mdu 2018 15 of of IN cord-014597-66vd2mdu 2018 16 CTE CTE NNP cord-014597-66vd2mdu 2018 17 cultures culture NNS cord-014597-66vd2mdu 2018 18 ) ) -RRB- cord-014597-66vd2mdu 2018 19 and and CC cord-014597-66vd2mdu 2018 20 inoculated inoculate VBN cord-014597-66vd2mdu 2018 21 in in IN cord-014597-66vd2mdu 2018 22 fresh fresh JJ cord-014597-66vd2mdu 2018 23 media medium NNS cord-014597-66vd2mdu 2018 24 . . . cord-014597-66vd2mdu 2019 1 The the DT cord-014597-66vd2mdu 2019 2 STE STE NNP cord-014597-66vd2mdu 2019 3 - - HYPH cord-014597-66vd2mdu 2019 4 cultures culture NNS cord-014597-66vd2mdu 2019 5 showed show VBD cord-014597-66vd2mdu 2019 6 improved improved JJ cord-014597-66vd2mdu 2019 7 viability viability NN cord-014597-66vd2mdu 2019 8 and and CC cord-014597-66vd2mdu 2019 9 higher high JJR cord-014597-66vd2mdu 2019 10 maximum maximum JJ cord-014597-66vd2mdu 2019 11 VCD vcd NN cord-014597-66vd2mdu 2019 12 as as IN cord-014597-66vd2mdu 2019 13 compared compare VBN cord-014597-66vd2mdu 2019 14 to to IN cord-014597-66vd2mdu 2019 15 CTE CTE NNP cord-014597-66vd2mdu 2019 16 - - HYPH cord-014597-66vd2mdu 2019 17 cultures culture NNS cord-014597-66vd2mdu 2019 18 ( ( -LRB- cord-014597-66vd2mdu 2019 19 Fig Fig NNP cord-014597-66vd2mdu 2019 20 . . . cord-014597-66vd2mdu 2019 21 1a 1a CD cord-014597-66vd2mdu 2019 22 ) ) -RRB- cord-014597-66vd2mdu 2019 23 . . . cord-014597-66vd2mdu 2020 1 The the DT cord-014597-66vd2mdu 2020 2 fold fold JJ cord-014597-66vd2mdu 2020 3 increase increase NN cord-014597-66vd2mdu 2020 4 in in IN cord-014597-66vd2mdu 2020 5 IgG igg NN cord-014597-66vd2mdu 2020 6 titers titer NNS cord-014597-66vd2mdu 2020 7 was be VBD cord-014597-66vd2mdu 2020 8 not not RB cord-014597-66vd2mdu 2020 9 sustained sustain VBN cord-014597-66vd2mdu 2020 10 beyond beyond IN cord-014597-66vd2mdu 2020 11 day day NN cord-014597-66vd2mdu 2020 12 1 1 CD cord-014597-66vd2mdu 2020 13 - - SYM cord-014597-66vd2mdu 2020 14 2 2 CD cord-014597-66vd2mdu 2020 15 in in IN cord-014597-66vd2mdu 2020 16 STEcultures steculture NNS cord-014597-66vd2mdu 2021 1 ( ( -LRB- cord-014597-66vd2mdu 2021 2 Fig Fig NNP cord-014597-66vd2mdu 2021 3 . . . cord-014597-66vd2mdu 2021 4 1d 1d CD cord-014597-66vd2mdu 2021 5 ) ) -RRB- cord-014597-66vd2mdu 2022 1 but but CC cord-014597-66vd2mdu 2022 2 significant significant JJ cord-014597-66vd2mdu 2022 3 increase increase NN cord-014597-66vd2mdu 2022 4 in in IN cord-014597-66vd2mdu 2022 5 productivity productivity NN cord-014597-66vd2mdu 2022 6 was be VBD cord-014597-66vd2mdu 2022 7 seen see VBN cord-014597-66vd2mdu 2022 8 in in IN cord-014597-66vd2mdu 2022 9 the the DT cord-014597-66vd2mdu 2022 10 initial initial JJ cord-014597-66vd2mdu 2022 11 phase phase NN cord-014597-66vd2mdu 2022 12 ( ( -LRB- cord-014597-66vd2mdu 2022 13 Fig Fig NNP cord-014597-66vd2mdu 2022 14 . . . cord-014597-66vd2mdu 2022 15 1e 1e LS cord-014597-66vd2mdu 2022 16 ) ) -RRB- cord-014597-66vd2mdu 2022 17 . . . cord-014597-66vd2mdu 2023 1 Further further RB cord-014597-66vd2mdu 2023 2 , , , cord-014597-66vd2mdu 2023 3 the the DT cord-014597-66vd2mdu 2023 4 cells cell NNS cord-014597-66vd2mdu 2023 5 were be VBD cord-014597-66vd2mdu 2023 6 adapted adapt VBN cord-014597-66vd2mdu 2023 7 over over IN cord-014597-66vd2mdu 2023 8 25 25 CD cord-014597-66vd2mdu 2023 9 continuous continuous JJ cord-014597-66vd2mdu 2023 10 generations generation NNS cord-014597-66vd2mdu 2023 11 under under IN cord-014597-66vd2mdu 2023 12 30ng 30ng NN cord-014597-66vd2mdu 2023 13 / / SYM cord-014597-66vd2mdu 2023 14 mL ml NN cord-014597-66vd2mdu 2023 15 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2023 16 . . . cord-014597-66vd2mdu 2024 1 The the DT cord-014597-66vd2mdu 2024 2 adapted adapt VBN cord-014597-66vd2mdu 2024 3 cells cell NNS cord-014597-66vd2mdu 2024 4 had have VBD cord-014597-66vd2mdu 2024 5 overall overall RB cord-014597-66vd2mdu 2024 6 1.3-fold 1.3-fold CD cord-014597-66vd2mdu 2024 7 higher high JJR cord-014597-66vd2mdu 2024 8 productivity productivity NN cord-014597-66vd2mdu 2024 9 , , , cord-014597-66vd2mdu 2024 10 as as IN cord-014597-66vd2mdu 2024 11 compared compare VBN cord-014597-66vd2mdu 2024 12 to to TO cord-014597-66vd2mdu 2024 13 control control VB cord-014597-66vd2mdu 2024 14 ( ( -LRB- cord-014597-66vd2mdu 2024 15 Fig Fig NNP cord-014597-66vd2mdu 2024 16 . . . cord-014597-66vd2mdu 2024 17 1f 1f CD cord-014597-66vd2mdu 2024 18 ) ) -RRB- cord-014597-66vd2mdu 2024 19 , , , cord-014597-66vd2mdu 2024 20 in in IN cord-014597-66vd2mdu 2024 21 a a DT cord-014597-66vd2mdu 2024 22 batch batch NN cord-014597-66vd2mdu 2024 23 culture culture NN cord-014597-66vd2mdu 2024 24 . . . cord-014597-66vd2mdu 2025 1 To to TO cord-014597-66vd2mdu 2025 2 understand understand VB cord-014597-66vd2mdu 2025 3 the the DT cord-014597-66vd2mdu 2025 4 molecular molecular JJ cord-014597-66vd2mdu 2025 5 basis basis NN cord-014597-66vd2mdu 2025 6 of of IN cord-014597-66vd2mdu 2025 7 increase increase NN cord-014597-66vd2mdu 2025 8 in in IN cord-014597-66vd2mdu 2025 9 productivity productivity NN cord-014597-66vd2mdu 2025 10 , , , cord-014597-66vd2mdu 2025 11 mRNA mrna NN cord-014597-66vd2mdu 2025 12 expression expression NN cord-014597-66vd2mdu 2025 13 level level NN cord-014597-66vd2mdu 2025 14 of of IN cord-014597-66vd2mdu 2025 15 key key JJ cord-014597-66vd2mdu 2025 16 genes gene NNS cord-014597-66vd2mdu 2025 17 was be VBD cord-014597-66vd2mdu 2025 18 determined determine VBN cord-014597-66vd2mdu 2025 19 . . . cord-014597-66vd2mdu 2026 1 XBP1s XBP1s NNP cord-014597-66vd2mdu 2026 2 is be VBZ cord-014597-66vd2mdu 2026 3 a a DT cord-014597-66vd2mdu 2026 4 transcription transcription NN cord-014597-66vd2mdu 2026 5 factor factor NN cord-014597-66vd2mdu 2026 6 involved involve VBN cord-014597-66vd2mdu 2026 7 in in IN cord-014597-66vd2mdu 2026 8 activation activation NN cord-014597-66vd2mdu 2026 9 of of IN cord-014597-66vd2mdu 2026 10 chaperones chaperone NNS cord-014597-66vd2mdu 2026 11 ( ( -LRB- cord-014597-66vd2mdu 2026 12 like like IN cord-014597-66vd2mdu 2026 13 Grp78 Grp78 NNP cord-014597-66vd2mdu 2026 14 , , , cord-014597-66vd2mdu 2026 15 Calreticulin Calreticulin NNP cord-014597-66vd2mdu 2026 16 ) ) -RRB- cord-014597-66vd2mdu 2026 17 and and CC cord-014597-66vd2mdu 2026 18 apoptotic apoptotic JJ cord-014597-66vd2mdu 2026 19 genes gene NNS cord-014597-66vd2mdu 2026 20 ( ( -LRB- cord-014597-66vd2mdu 2026 21 such such JJ cord-014597-66vd2mdu 2026 22 as as IN cord-014597-66vd2mdu 2026 23 CHOP CHOP NNP cord-014597-66vd2mdu 2026 24 ) ) -RRB- cord-014597-66vd2mdu 2026 25 . . . cord-014597-66vd2mdu 2027 1 Significant significant JJ cord-014597-66vd2mdu 2027 2 increase increase NN cord-014597-66vd2mdu 2027 3 in in IN cord-014597-66vd2mdu 2027 4 the the DT cord-014597-66vd2mdu 2027 5 levels level NNS cord-014597-66vd2mdu 2027 6 of of IN cord-014597-66vd2mdu 2027 7 calreticulin calreticulin NNP cord-014597-66vd2mdu 2027 8 was be VBD cord-014597-66vd2mdu 2027 9 seen see VBN cord-014597-66vd2mdu 2027 10 on on IN cord-014597-66vd2mdu 2027 11 treatment treatment NN cord-014597-66vd2mdu 2027 12 with with IN cord-014597-66vd2mdu 2027 13 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2027 14 ( ( -LRB- cord-014597-66vd2mdu 2027 15 Fig Fig NNP cord-014597-66vd2mdu 2027 16 . . . cord-014597-66vd2mdu 2027 17 1 1 CD cord-014597-66vd2mdu 2027 18 g g NN cord-014597-66vd2mdu 2027 19 ) ) -RRB- cord-014597-66vd2mdu 2027 20 . . . cord-014597-66vd2mdu 2028 1 Both both CC cord-014597-66vd2mdu 2028 2 XBP1s XBP1s NNP cord-014597-66vd2mdu 2028 3 and and CC cord-014597-66vd2mdu 2029 1 Grp78 Grp78 NNP cord-014597-66vd2mdu 2029 2 were be VBD cord-014597-66vd2mdu 2029 3 marginally marginally RB cord-014597-66vd2mdu 2029 4 induced induce VBN cord-014597-66vd2mdu 2029 5 when when WRB cord-014597-66vd2mdu 2029 6 treated treat VBN cord-014597-66vd2mdu 2029 7 with with IN cord-014597-66vd2mdu 2029 8 30ng 30ng NN cord-014597-66vd2mdu 2029 9 / / SYM cord-014597-66vd2mdu 2029 10 mL ml NN cord-014597-66vd2mdu 2029 11 of of IN cord-014597-66vd2mdu 2029 12 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2029 13 in in IN cord-014597-66vd2mdu 2029 14 both both DT cord-014597-66vd2mdu 2029 15 CTE CTE NNP cord-014597-66vd2mdu 2029 16 - - HYPH cord-014597-66vd2mdu 2029 17 and and CC cord-014597-66vd2mdu 2029 18 STE STE NNP cord-014597-66vd2mdu 2029 19 - - HYPH cord-014597-66vd2mdu 2029 20 cultures culture NNS cord-014597-66vd2mdu 2029 21 ( ( -LRB- cord-014597-66vd2mdu 2029 22 Fig Fig NNP cord-014597-66vd2mdu 2029 23 . . . cord-014597-66vd2mdu 2029 24 1h 1h CD cord-014597-66vd2mdu 2029 25 ) ) -RRB- cord-014597-66vd2mdu 2029 26 , , , cord-014597-66vd2mdu 2029 27 and and CC cord-014597-66vd2mdu 2029 28 significantly significantly RB cord-014597-66vd2mdu 2029 29 up up RB cord-014597-66vd2mdu 2029 30 - - HYPH cord-014597-66vd2mdu 2029 31 regulated regulate VBN cord-014597-66vd2mdu 2029 32 when when WRB cord-014597-66vd2mdu 2029 33 treated treat VBN cord-014597-66vd2mdu 2029 34 with with IN cord-014597-66vd2mdu 2029 35 500ng 500ng NNP cord-014597-66vd2mdu 2029 36 / / SYM cord-014597-66vd2mdu 2029 37 mL ml NN cord-014597-66vd2mdu 2029 38 of of IN cord-014597-66vd2mdu 2029 39 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2029 40 . . . cord-014597-66vd2mdu 2030 1 The the DT cord-014597-66vd2mdu 2030 2 CHOP chop NN cord-014597-66vd2mdu 2030 3 mRNA mrna NN cord-014597-66vd2mdu 2030 4 levels level NNS cord-014597-66vd2mdu 2030 5 also also RB cord-014597-66vd2mdu 2030 6 increase increase VBP cord-014597-66vd2mdu 2030 7 with with IN cord-014597-66vd2mdu 2030 8 increasing increase VBG cord-014597-66vd2mdu 2030 9 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2030 10 concentrations concentration NNS cord-014597-66vd2mdu 2030 11 , , , cord-014597-66vd2mdu 2030 12 with with IN cord-014597-66vd2mdu 2030 13 levels level NNS cord-014597-66vd2mdu 2030 14 in in IN cord-014597-66vd2mdu 2030 15 STE STE NNP cord-014597-66vd2mdu 2030 16 - - HYPH cord-014597-66vd2mdu 2030 17 cultures culture NNS cord-014597-66vd2mdu 2030 18 lower low JJR cord-014597-66vd2mdu 2030 19 than than IN cord-014597-66vd2mdu 2030 20 CTE CTE NNP cord-014597-66vd2mdu 2030 21 - - HYPH cord-014597-66vd2mdu 2030 22 cultures culture NNS cord-014597-66vd2mdu 2030 23 ( ( -LRB- cord-014597-66vd2mdu 2030 24 Fig Fig NNP cord-014597-66vd2mdu 2030 25 . . . cord-014597-66vd2mdu 2030 26 1h 1h CD cord-014597-66vd2mdu 2030 27 ) ) -RRB- cord-014597-66vd2mdu 2030 28 . . . cord-014597-66vd2mdu 2031 1 The the DT cord-014597-66vd2mdu 2031 2 results result NNS cord-014597-66vd2mdu 2031 3 suggest suggest VBP cord-014597-66vd2mdu 2031 4 that that IN cord-014597-66vd2mdu 2031 5 UPR UPR NNP cord-014597-66vd2mdu 2031 6 induction induction NN cord-014597-66vd2mdu 2031 7 may may MD cord-014597-66vd2mdu 2031 8 be be VB cord-014597-66vd2mdu 2031 9 important important JJ cord-014597-66vd2mdu 2031 10 to to TO cord-014597-66vd2mdu 2031 11 increase increase VB cord-014597-66vd2mdu 2031 12 productivity productivity NN cord-014597-66vd2mdu 2031 13 in in IN cord-014597-66vd2mdu 2031 14 these these DT cord-014597-66vd2mdu 2031 15 CTE CTE NNP cord-014597-66vd2mdu 2031 16 / / SYM cord-014597-66vd2mdu 2031 17 STE STE NNP cord-014597-66vd2mdu 2031 18 - - HYPH cord-014597-66vd2mdu 2031 19 cultures culture NNS cord-014597-66vd2mdu 2031 20 . . . cord-014597-66vd2mdu 2032 1 Note note VB cord-014597-66vd2mdu 2032 2 that that IN cord-014597-66vd2mdu 2032 3 , , , cord-014597-66vd2mdu 2032 4 tunicamycin tunicamycin NNP cord-014597-66vd2mdu 2032 5 had have VBD cord-014597-66vd2mdu 2032 6 no no DT cord-014597-66vd2mdu 2032 7 effect effect NN cord-014597-66vd2mdu 2032 8 on on IN cord-014597-66vd2mdu 2032 9 the the DT cord-014597-66vd2mdu 2032 10 expression expression NN cord-014597-66vd2mdu 2032 11 levels level NNS cord-014597-66vd2mdu 2032 12 of of IN cord-014597-66vd2mdu 2032 13 IgG igg NN cord-014597-66vd2mdu 2032 14 heavy heavy JJ cord-014597-66vd2mdu 2032 15 - - HYPH cord-014597-66vd2mdu 2032 16 chain chain NN cord-014597-66vd2mdu 2032 17 , , , cord-014597-66vd2mdu 2032 18 thus thus RB cord-014597-66vd2mdu 2032 19 eliminating eliminate VBG cord-014597-66vd2mdu 2032 20 the the DT cord-014597-66vd2mdu 2032 21 involvement involvement NN cord-014597-66vd2mdu 2032 22 of of IN cord-014597-66vd2mdu 2032 23 IgGHC IgGHC NNP cord-014597-66vd2mdu 2032 24 - - HYPH cord-014597-66vd2mdu 2032 25 mRNA mRNA NNP cord-014597-66vd2mdu 2032 26 in in IN cord-014597-66vd2mdu 2032 27 increasing increase VBG cord-014597-66vd2mdu 2032 28 productivity productivity NN cord-014597-66vd2mdu 2032 29 ( ( -LRB- cord-014597-66vd2mdu 2032 30 Fig Fig NNP cord-014597-66vd2mdu 2032 31 . . . cord-014597-66vd2mdu 2032 32 1i 1i LS cord-014597-66vd2mdu 2032 33 ) ) -RRB- cord-014597-66vd2mdu 2032 34 . . . cord-014597-66vd2mdu 2033 1 Tunicamycin Tunicamycin NNP cord-014597-66vd2mdu 2033 2 induced induce VBN cord-014597-66vd2mdu 2033 3 ER ER NNP cord-014597-66vd2mdu 2033 4 - - HYPH cord-014597-66vd2mdu 2033 5 stress stress NN cord-014597-66vd2mdu 2033 6 increased increase VBD cord-014597-66vd2mdu 2033 7 productivity productivity NN cord-014597-66vd2mdu 2033 8 in in IN cord-014597-66vd2mdu 2033 9 the the DT cord-014597-66vd2mdu 2033 10 initial initial JJ cord-014597-66vd2mdu 2033 11 phase phase NN cord-014597-66vd2mdu 2033 12 of of IN cord-014597-66vd2mdu 2033 13 the the DT cord-014597-66vd2mdu 2033 14 culture culture NN cord-014597-66vd2mdu 2033 15 and and CC cord-014597-66vd2mdu 2033 16 enhanced enhance VBN cord-014597-66vd2mdu 2033 17 UPR UPR NNP cord-014597-66vd2mdu 2033 18 - - HYPH cord-014597-66vd2mdu 2033 19 mediated mediate VBN cord-014597-66vd2mdu 2033 20 folding folding NN cord-014597-66vd2mdu 2033 21 capacity capacity NN cord-014597-66vd2mdu 2033 22 can can MD cord-014597-66vd2mdu 2033 23 be be VB cord-014597-66vd2mdu 2033 24 attributed attribute VBN cord-014597-66vd2mdu 2033 25 as as IN cord-014597-66vd2mdu 2033 26 one one CD cord-014597-66vd2mdu 2033 27 of of IN cord-014597-66vd2mdu 2033 28 the the DT cord-014597-66vd2mdu 2033 29 reasons reason NNS cord-014597-66vd2mdu 2033 30 for for IN cord-014597-66vd2mdu 2033 31 it -PRON- PRP cord-014597-66vd2mdu 2033 32 . . . cord-014597-66vd2mdu 2034 1 At at IN cord-014597-66vd2mdu 2034 2 lower low JJR cord-014597-66vd2mdu 2034 3 concentrations concentration NNS cord-014597-66vd2mdu 2034 4 of of IN cord-014597-66vd2mdu 2034 5 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2034 6 , , , cord-014597-66vd2mdu 2034 7 a a DT cord-014597-66vd2mdu 2034 8 fine fine JJ cord-014597-66vd2mdu 2034 9 balance balance NN cord-014597-66vd2mdu 2034 10 between between IN cord-014597-66vd2mdu 2034 11 optimum optimum JJ cord-014597-66vd2mdu 2034 12 UPR UPR NNP cord-014597-66vd2mdu 2034 13 induction induction NN cord-014597-66vd2mdu 2034 14 and and CC cord-014597-66vd2mdu 2034 15 apoptosis apoptosis NN cord-014597-66vd2mdu 2034 16 can can MD cord-014597-66vd2mdu 2034 17 be be VB cord-014597-66vd2mdu 2034 18 achieved achieve VBN cord-014597-66vd2mdu 2034 19 , , , cord-014597-66vd2mdu 2034 20 as as IN cord-014597-66vd2mdu 2034 21 seen see VBN cord-014597-66vd2mdu 2034 22 in in IN cord-014597-66vd2mdu 2034 23 30ng 30ng NN cord-014597-66vd2mdu 2034 24 / / SYM cord-014597-66vd2mdu 2034 25 mL ml NN cord-014597-66vd2mdu 2034 26 tunicamycin tunicamycin NNS cord-014597-66vd2mdu 2034 27 STE STE NNP cord-014597-66vd2mdu 2034 28 - - HYPH cord-014597-66vd2mdu 2034 29 cultures culture NNS cord-014597-66vd2mdu 2034 30 . . . cord-014597-66vd2mdu 2035 1 In in IN cord-014597-66vd2mdu 2035 2 summary summary NN cord-014597-66vd2mdu 2035 3 , , , cord-014597-66vd2mdu 2035 4 this this DT cord-014597-66vd2mdu 2035 5 study study NN cord-014597-66vd2mdu 2035 6 demonstrates demonstrate VBZ cord-014597-66vd2mdu 2035 7 an an DT cord-014597-66vd2mdu 2035 8 alternate alternate JJ cord-014597-66vd2mdu 2035 9 approach approach NN cord-014597-66vd2mdu 2035 10 to to TO cord-014597-66vd2mdu 2035 11 enhance enhance VB cord-014597-66vd2mdu 2035 12 productivity productivity NN cord-014597-66vd2mdu 2035 13 of of IN cord-014597-66vd2mdu 2035 14 current current JJ cord-014597-66vd2mdu 2035 15 industrial industrial JJ cord-014597-66vd2mdu 2035 16 cell cell NN cord-014597-66vd2mdu 2035 17 lines line NNS cord-014597-66vd2mdu 2035 18 . . . cord-014597-66vd2mdu 2036 1 Background background NN cord-014597-66vd2mdu 2036 2 Chinese chinese JJ cord-014597-66vd2mdu 2036 3 hamster hamster NN cord-014597-66vd2mdu 2036 4 ovary ovary NN cord-014597-66vd2mdu 2036 5 ( ( -LRB- cord-014597-66vd2mdu 2036 6 CHO CHO NNP cord-014597-66vd2mdu 2036 7 ) ) -RRB- cord-014597-66vd2mdu 2036 8 cells cell NNS cord-014597-66vd2mdu 2036 9 have have VBP cord-014597-66vd2mdu 2036 10 been be VBN cord-014597-66vd2mdu 2036 11 widely widely RB cord-014597-66vd2mdu 2036 12 used use VBN cord-014597-66vd2mdu 2036 13 for for IN cord-014597-66vd2mdu 2036 14 the the DT cord-014597-66vd2mdu 2036 15 large large JJ cord-014597-66vd2mdu 2036 16 - - HYPH cord-014597-66vd2mdu 2036 17 scale scale NN cord-014597-66vd2mdu 2036 18 production production NN cord-014597-66vd2mdu 2036 19 of of IN cord-014597-66vd2mdu 2036 20 biopharmaceuticals biopharmaceutical NNS cord-014597-66vd2mdu 2036 21 [ [ -LRB- cord-014597-66vd2mdu 2036 22 1 1 CD cord-014597-66vd2mdu 2036 23 ] ] -RRB- cord-014597-66vd2mdu 2036 24 . . . cord-014597-66vd2mdu 2037 1 To to TO cord-014597-66vd2mdu 2037 2 construct construct VB cord-014597-66vd2mdu 2037 3 antibody antibody NN cord-014597-66vd2mdu 2037 4 - - HYPH cord-014597-66vd2mdu 2037 5 producing produce VBG cord-014597-66vd2mdu 2037 6 CHO CHO NNP cord-014597-66vd2mdu 2037 7 cells cell NNS cord-014597-66vd2mdu 2037 8 , , , cord-014597-66vd2mdu 2037 9 exogenous exogenous JJ cord-014597-66vd2mdu 2037 10 genes gene NNS cord-014597-66vd2mdu 2037 11 encoding encode VBG cord-014597-66vd2mdu 2037 12 antibodies antibody NNS cord-014597-66vd2mdu 2037 13 are be VBP cord-014597-66vd2mdu 2037 14 usually usually RB cord-014597-66vd2mdu 2037 15 integrated integrate VBN cord-014597-66vd2mdu 2037 16 into into IN cord-014597-66vd2mdu 2037 17 unspecified unspecified JJ cord-014597-66vd2mdu 2037 18 regions region NNS cord-014597-66vd2mdu 2037 19 of of IN cord-014597-66vd2mdu 2037 20 chromosomes chromosome NNS cord-014597-66vd2mdu 2037 21 ( ( -LRB- cord-014597-66vd2mdu 2037 22 random random JJ cord-014597-66vd2mdu 2037 23 integration integration NN cord-014597-66vd2mdu 2037 24 ) ) -RRB- cord-014597-66vd2mdu 2037 25 . . . cord-014597-66vd2mdu 2038 1 However however RB cord-014597-66vd2mdu 2038 2 , , , cord-014597-66vd2mdu 2038 3 the the DT cord-014597-66vd2mdu 2038 4 chromatin chromatin NN cord-014597-66vd2mdu 2038 5 structure structure NN cord-014597-66vd2mdu 2038 6 differs differ VBZ cord-014597-66vd2mdu 2038 7 depending depend VBG cord-014597-66vd2mdu 2038 8 on on IN cord-014597-66vd2mdu 2038 9 the the DT cord-014597-66vd2mdu 2038 10 location location NN cord-014597-66vd2mdu 2038 11 of of IN cord-014597-66vd2mdu 2038 12 the the DT cord-014597-66vd2mdu 2038 13 chromosomal chromosomal JJ cord-014597-66vd2mdu 2038 14 region region NN cord-014597-66vd2mdu 2038 15 , , , cord-014597-66vd2mdu 2038 16 which which WDT cord-014597-66vd2mdu 2038 17 affects affect VBZ cord-014597-66vd2mdu 2038 18 the the DT cord-014597-66vd2mdu 2038 19 expression expression NN cord-014597-66vd2mdu 2038 20 level level NN cord-014597-66vd2mdu 2038 21 of of IN cord-014597-66vd2mdu 2038 22 the the DT cord-014597-66vd2mdu 2038 23 gene gene NN cord-014597-66vd2mdu 2038 24 of of IN cord-014597-66vd2mdu 2038 25 interest interest NN cord-014597-66vd2mdu 2038 26 [ [ -LRB- cord-014597-66vd2mdu 2038 27 2 2 CD cord-014597-66vd2mdu 2038 28 ] ] -RRB- cord-014597-66vd2mdu 2038 29 . . . cord-014597-66vd2mdu 2039 1 Recently recently RB cord-014597-66vd2mdu 2039 2 , , , cord-014597-66vd2mdu 2039 3 gene gene NN cord-014597-66vd2mdu 2039 4 - - HYPH cord-014597-66vd2mdu 2039 5 targeting target VBG cord-014597-66vd2mdu 2039 6 methods method NNS cord-014597-66vd2mdu 2039 7 that that WDT cord-014597-66vd2mdu 2039 8 enable enable VBP cord-014597-66vd2mdu 2039 9 site site NN cord-014597-66vd2mdu 2039 10 - - HYPH cord-014597-66vd2mdu 2039 11 specific specific JJ cord-014597-66vd2mdu 2039 12 integration integration NN cord-014597-66vd2mdu 2039 13 of of IN cord-014597-66vd2mdu 2039 14 expression expression NN cord-014597-66vd2mdu 2039 15 vectors vector NNS cord-014597-66vd2mdu 2039 16 have have VBP cord-014597-66vd2mdu 2039 17 been be VBN cord-014597-66vd2mdu 2039 18 developed develop VBN cord-014597-66vd2mdu 2039 19 . . . cord-014597-66vd2mdu 2040 1 However however RB cord-014597-66vd2mdu 2040 2 , , , cord-014597-66vd2mdu 2040 3 the the DT cord-014597-66vd2mdu 2040 4 regions region NNS cord-014597-66vd2mdu 2040 5 that that WDT cord-014597-66vd2mdu 2040 6 are be VBP cord-014597-66vd2mdu 2040 7 most most RBS cord-014597-66vd2mdu 2040 8 efficient efficient JJ cord-014597-66vd2mdu 2040 9 for for IN cord-014597-66vd2mdu 2040 10 exogenous exogenous JJ cord-014597-66vd2mdu 2040 11 gene gene NN cord-014597-66vd2mdu 2040 12 expression expression NN cord-014597-66vd2mdu 2040 13 have have VBP cord-014597-66vd2mdu 2040 14 not not RB cord-014597-66vd2mdu 2040 15 been be VBN cord-014597-66vd2mdu 2040 16 clarified clarify VBN cord-014597-66vd2mdu 2040 17 . . . cord-014597-66vd2mdu 2041 1 We -PRON- PRP cord-014597-66vd2mdu 2041 2 previously previously RB cord-014597-66vd2mdu 2041 3 constructed construct VBD cord-014597-66vd2mdu 2041 4 a a DT cord-014597-66vd2mdu 2041 5 CHO CHO NNP cord-014597-66vd2mdu 2041 6 genomic genomic JJ cord-014597-66vd2mdu 2041 7 bacterial bacterial JJ cord-014597-66vd2mdu 2041 8 artificial artificial JJ cord-014597-66vd2mdu 2041 9 chromosome chromosome NN cord-014597-66vd2mdu 2041 10 ( ( -LRB- cord-014597-66vd2mdu 2041 11 BAC BAC NNP cord-014597-66vd2mdu 2041 12 ) ) -RRB- cord-014597-66vd2mdu 2041 13 library library NN cord-014597-66vd2mdu 2041 14 generated generate VBN cord-014597-66vd2mdu 2041 15 from from IN cord-014597-66vd2mdu 2041 16 the the DT cord-014597-66vd2mdu 2041 17 recombinant recombinant JJ cord-014597-66vd2mdu 2041 18 CHO CHO NNP cord-014597-66vd2mdu 2041 19 - - HYPH cord-014597-66vd2mdu 2041 20 DG44 DG44 NNP cord-014597-66vd2mdu 2041 21 cell cell NN cord-014597-66vd2mdu 2041 22 line line NN cord-014597-66vd2mdu 2041 23 . . . cord-014597-66vd2mdu 2042 1 It -PRON- PRP cord-014597-66vd2mdu 2042 2 was be VBD cord-014597-66vd2mdu 2042 3 expected expect VBN cord-014597-66vd2mdu 2042 4 to to TO cord-014597-66vd2mdu 2042 5 cover cover VB cord-014597-66vd2mdu 2042 6 the the DT cord-014597-66vd2mdu 2042 7 entire entire JJ cord-014597-66vd2mdu 2042 8 CHO CHO NNP cord-014597-66vd2mdu 2042 9 genome genome NN cord-014597-66vd2mdu 2042 10 five five CD cord-014597-66vd2mdu 2042 11 times time NNS cord-014597-66vd2mdu 2042 12 . . . cord-014597-66vd2mdu 2043 1 The the DT cord-014597-66vd2mdu 2043 2 20 20 CD cord-014597-66vd2mdu 2043 3 chromosomes chromosome NNS cord-014597-66vd2mdu 2043 4 in in IN cord-014597-66vd2mdu 2043 5 CHO CHO NNP cord-014597-66vd2mdu 2043 6 - - HYPH cord-014597-66vd2mdu 2043 7 DG44 DG44 NNP cord-014597-66vd2mdu 2043 8 cells cell NNS cord-014597-66vd2mdu 2043 9 were be VBD cord-014597-66vd2mdu 2043 10 aligned align VBN cord-014597-66vd2mdu 2043 11 in in IN cord-014597-66vd2mdu 2043 12 decreasing decrease VBG cord-014597-66vd2mdu 2043 13 order order NN cord-014597-66vd2mdu 2043 14 of of IN cord-014597-66vd2mdu 2043 15 size size NN cord-014597-66vd2mdu 2043 16 and and CC cord-014597-66vd2mdu 2043 17 assigned assign VBN cord-014597-66vd2mdu 2043 18 letters letter NNS cord-014597-66vd2mdu 2043 19 from from IN cord-014597-66vd2mdu 2043 20 A a NN cord-014597-66vd2mdu 2043 21 to to IN cord-014597-66vd2mdu 2043 22 T T NNP cord-014597-66vd2mdu 2043 23 [ [ -LRB- cord-014597-66vd2mdu 2043 24 3 3 CD cord-014597-66vd2mdu 2043 25 ] ] -RRB- cord-014597-66vd2mdu 2043 26 . . . cord-014597-66vd2mdu 2044 1 Three three CD cord-014597-66vd2mdu 2044 2 hundred hundred CD cord-014597-66vd2mdu 2044 3 and and CC cord-014597-66vd2mdu 2044 4 four four CD cord-014597-66vd2mdu 2044 5 BAC BAC NNP cord-014597-66vd2mdu 2044 6 clones clone NNS cord-014597-66vd2mdu 2044 7 were be VBD cord-014597-66vd2mdu 2044 8 mapped map VBN cord-014597-66vd2mdu 2044 9 to to IN cord-014597-66vd2mdu 2044 10 every every DT cord-014597-66vd2mdu 2044 11 chromosome chromosome NN cord-014597-66vd2mdu 2044 12 of of IN cord-014597-66vd2mdu 2044 13 CHO CHO NNP cord-014597-66vd2mdu 2044 14 - - HYPH cord-014597-66vd2mdu 2044 15 DG44 DG44 NNP cord-014597-66vd2mdu 2044 16 . . . cord-014597-66vd2mdu 2045 1 Among among IN cord-014597-66vd2mdu 2045 2 the the DT cord-014597-66vd2mdu 2045 3 karyotypes karyotype NNS cord-014597-66vd2mdu 2045 4 of of IN cord-014597-66vd2mdu 2045 5 CHO CHO NNP cord-014597-66vd2mdu 2045 6 - - HYPH cord-014597-66vd2mdu 2045 7 DG44 DG44 NNP cord-014597-66vd2mdu 2045 8 , , , cord-014597-66vd2mdu 2045 9 CHO CHO NNP cord-014597-66vd2mdu 2045 10 - - HYPH cord-014597-66vd2mdu 2045 11 K1 K1 NNP cord-014597-66vd2mdu 2045 12 and and CC cord-014597-66vd2mdu 2045 13 primary primary JJ cord-014597-66vd2mdu 2045 14 Chinese chinese JJ cord-014597-66vd2mdu 2045 15 hamster hamster NN cord-014597-66vd2mdu 2045 16 cells cell NNS cord-014597-66vd2mdu 2045 17 , , , cord-014597-66vd2mdu 2046 1 chromosomes chromosome NNS cord-014597-66vd2mdu 2046 2 A A NNP cord-014597-66vd2mdu 2046 3 and and CC cord-014597-66vd2mdu 2046 4 B b NN cord-014597-66vd2mdu 2046 5 are be VBP cord-014597-66vd2mdu 2046 6 considered consider VBN cord-014597-66vd2mdu 2046 7 as as IN cord-014597-66vd2mdu 2046 8 the the DT cord-014597-66vd2mdu 2046 9 sole sole NN cord-014597-66vd2mdu 2046 10 paired pair VBN cord-014597-66vd2mdu 2046 11 chromosomes chromosome NNS cord-014597-66vd2mdu 2046 12 corresponding correspond VBG cord-014597-66vd2mdu 2046 13 to to IN cord-014597-66vd2mdu 2046 14 chromosome chromosome NN cord-014597-66vd2mdu 2046 15 1 1 CD cord-014597-66vd2mdu 2046 16 in in IN cord-014597-66vd2mdu 2046 17 primary primary JJ cord-014597-66vd2mdu 2046 18 Chinese chinese JJ cord-014597-66vd2mdu 2046 19 hamster hamster NN cord-014597-66vd2mdu 2046 20 cells cell NNS cord-014597-66vd2mdu 2046 21 . . . cord-014597-66vd2mdu 2047 1 Hence hence RB cord-014597-66vd2mdu 2047 2 , , , cord-014597-66vd2mdu 2047 3 chromosomes chromosome VBZ cord-014597-66vd2mdu 2047 4 A a NN cord-014597-66vd2mdu 2047 5 and and CC cord-014597-66vd2mdu 2047 6 B b NN cord-014597-66vd2mdu 2047 7 are be VBP cord-014597-66vd2mdu 2047 8 considered consider VBN cord-014597-66vd2mdu 2047 9 to to TO cord-014597-66vd2mdu 2047 10 be be VB cord-014597-66vd2mdu 2047 11 stable stable JJ cord-014597-66vd2mdu 2047 12 [ [ -LRB- cord-014597-66vd2mdu 2047 13 4 4 CD cord-014597-66vd2mdu 2047 14 ] ] -RRB- cord-014597-66vd2mdu 2047 15 . . . cord-014597-66vd2mdu 2048 1 In in IN cord-014597-66vd2mdu 2048 2 this this DT cord-014597-66vd2mdu 2048 3 study study NN cord-014597-66vd2mdu 2048 4 , , , cord-014597-66vd2mdu 2048 5 we -PRON- PRP cord-014597-66vd2mdu 2048 6 constructed construct VBD cord-014597-66vd2mdu 2048 7 antibody antibody NN cord-014597-66vd2mdu 2048 8 - - HYPH cord-014597-66vd2mdu 2048 9 producing produce VBG cord-014597-66vd2mdu 2048 10 cells cell NNS cord-014597-66vd2mdu 2048 11 by by IN cord-014597-66vd2mdu 2048 12 using use VBG cord-014597-66vd2mdu 2048 13 a a DT cord-014597-66vd2mdu 2048 14 gene gene NN cord-014597-66vd2mdu 2048 15 - - HYPH cord-014597-66vd2mdu 2048 16 targeting targeting NN cord-014597-66vd2mdu 2048 17 method method NN cord-014597-66vd2mdu 2048 18 , , , cord-014597-66vd2mdu 2048 19 which which WDT cord-014597-66vd2mdu 2048 20 focused focus VBD cord-014597-66vd2mdu 2048 21 on on IN cord-014597-66vd2mdu 2048 22 the the DT cord-014597-66vd2mdu 2048 23 stable stable JJ cord-014597-66vd2mdu 2048 24 chromosomes chromosome NNS cord-014597-66vd2mdu 2048 25 . . . cord-014597-66vd2mdu 2049 1 A a DT cord-014597-66vd2mdu 2049 2 gene gene NN cord-014597-66vd2mdu 2049 3 map map NN cord-014597-66vd2mdu 2049 4 of of IN cord-014597-66vd2mdu 2049 5 chromosome chromosome NN cord-014597-66vd2mdu 2049 6 1 1 CD cord-014597-66vd2mdu 2049 7 was be VBD cord-014597-66vd2mdu 2049 8 constructed construct VBN cord-014597-66vd2mdu 2049 9 by by IN cord-014597-66vd2mdu 2049 10 combining combine VBG cord-014597-66vd2mdu 2049 11 the the DT cord-014597-66vd2mdu 2049 12 BAC bac NN cord-014597-66vd2mdu 2049 13 - - HYPH cord-014597-66vd2mdu 2049 14 fluorescence fluorescence NN cord-014597-66vd2mdu 2049 15 in in IN cord-014597-66vd2mdu 2049 16 situ situ NN cord-014597-66vd2mdu 2049 17 hybridization hybridization NN cord-014597-66vd2mdu 2049 18 ( ( -LRB- cord-014597-66vd2mdu 2049 19 FISH)-based fish)-based JJ cord-014597-66vd2mdu 2049 20 chromosome chromosome NN cord-014597-66vd2mdu 2049 21 physical physical JJ cord-014597-66vd2mdu 2049 22 map map NN cord-014597-66vd2mdu 2049 23 and and CC cord-014597-66vd2mdu 2049 24 sequence sequence NN cord-014597-66vd2mdu 2049 25 data datum NNS cord-014597-66vd2mdu 2049 26 of of IN cord-014597-66vd2mdu 2049 27 mapped map VBN cord-014597-66vd2mdu 2049 28 BAC BAC NNP cord-014597-66vd2mdu 2049 29 clones clone NNS cord-014597-66vd2mdu 2049 30 . . . cord-014597-66vd2mdu 2050 1 The the DT cord-014597-66vd2mdu 2050 2 sequences sequence NNS cord-014597-66vd2mdu 2050 3 of of IN cord-014597-66vd2mdu 2050 4 BAC BAC NNP cord-014597-66vd2mdu 2050 5 clones clone NNS cord-014597-66vd2mdu 2050 6 were be VBD cord-014597-66vd2mdu 2050 7 searched search VBN cord-014597-66vd2mdu 2050 8 by by IN cord-014597-66vd2mdu 2050 9 BLAST blast NN cord-014597-66vd2mdu 2050 10 with with IN cord-014597-66vd2mdu 2050 11 NCBI NCBI NNP cord-014597-66vd2mdu 2050 12 and and CC cord-014597-66vd2mdu 2050 13 CHOgenome.org CHOgenome.org NNP cord-014597-66vd2mdu 2050 14 databases database NNS cord-014597-66vd2mdu 2050 15 . . . cord-014597-66vd2mdu 2051 1 Three three CD cord-014597-66vd2mdu 2051 2 different different JJ cord-014597-66vd2mdu 2051 3 regions region NNS cord-014597-66vd2mdu 2051 4 on on IN cord-014597-66vd2mdu 2051 5 chromosomes chromosome NNS cord-014597-66vd2mdu 2051 6 A a NN cord-014597-66vd2mdu 2051 7 and and CC cord-014597-66vd2mdu 2051 8 B B NNP cord-014597-66vd2mdu 2051 9 were be VBD cord-014597-66vd2mdu 2051 10 selected select VBN cord-014597-66vd2mdu 2051 11 based base VBN cord-014597-66vd2mdu 2051 12 on on IN cord-014597-66vd2mdu 2051 13 CHO CHO NNP cord-014597-66vd2mdu 2051 14 genomic genomic JJ cord-014597-66vd2mdu 2051 15 BAC BAC NNP cord-014597-66vd2mdu 2051 16 library library NN cord-014597-66vd2mdu 2051 17 sequences sequence NNS cord-014597-66vd2mdu 2051 18 as as IN cord-014597-66vd2mdu 2051 19 target target NN cord-014597-66vd2mdu 2051 20 sites site NNS cord-014597-66vd2mdu 2051 21 . . . cord-014597-66vd2mdu 2052 1 CHO CHO NNP cord-014597-66vd2mdu 2052 2 - - HYPH cord-014597-66vd2mdu 2052 3 K1 K1 NNP cord-014597-66vd2mdu 2052 4 cells cell NNS cord-014597-66vd2mdu 2052 5 were be VBD cord-014597-66vd2mdu 2052 6 stably stably RB cord-014597-66vd2mdu 2052 7 transfected transfecte VBN cord-014597-66vd2mdu 2052 8 by by IN cord-014597-66vd2mdu 2052 9 lipofection lipofection NN cord-014597-66vd2mdu 2052 10 . . . cord-014597-66vd2mdu 2053 1 The the DT cord-014597-66vd2mdu 2053 2 target target NN cord-014597-66vd2mdu 2053 3 sequences sequence NNS cord-014597-66vd2mdu 2053 4 were be VBD cord-014597-66vd2mdu 2053 5 broken break VBN cord-014597-66vd2mdu 2053 6 using use VBG cord-014597-66vd2mdu 2053 7 the the DT cord-014597-66vd2mdu 2053 8 clustered cluster VBN cord-014597-66vd2mdu 2053 9 regularly regularly RB cord-014597-66vd2mdu 2053 10 interspaced interspace VBD cord-014597-66vd2mdu 2053 11 short short JJ cord-014597-66vd2mdu 2053 12 palindromic palindromic JJ cord-014597-66vd2mdu 2053 13 repeats repeat NNS cord-014597-66vd2mdu 2054 1 ( ( -LRB- cord-014597-66vd2mdu 2054 2 CRISPR)/CRISPR CRISPR)/CRISPR NNP cord-014597-66vd2mdu 2054 3 - - HYPH cord-014597-66vd2mdu 2054 4 associated associate VBN cord-014597-66vd2mdu 2054 5 protein protein NN cord-014597-66vd2mdu 2054 6 9 9 CD cord-014597-66vd2mdu 2054 7 ( ( -LRB- cord-014597-66vd2mdu 2054 8 Cas9 Cas9 NNP cord-014597-66vd2mdu 2054 9 ) ) -RRB- cord-014597-66vd2mdu 2054 10 system system NN cord-014597-66vd2mdu 2054 11 and and CC cord-014597-66vd2mdu 2054 12 humanized humanize VBN cord-014597-66vd2mdu 2054 13 IgG1 IgG1 NNP cord-014597-66vd2mdu 2054 14 genes gene NNS cord-014597-66vd2mdu 2054 15 were be VBD cord-014597-66vd2mdu 2054 16 integrated integrate VBN cord-014597-66vd2mdu 2054 17 by by IN cord-014597-66vd2mdu 2054 18 non non JJ cord-014597-66vd2mdu 2054 19 - - JJ cord-014597-66vd2mdu 2054 20 homologous homologous JJ cord-014597-66vd2mdu 2054 21 end end NN cord-014597-66vd2mdu 2054 22 joining join VBG cord-014597-66vd2mdu 2054 23 recombination recombination NN cord-014597-66vd2mdu 2054 24 . . . cord-014597-66vd2mdu 2055 1 Transfection transfection NN cord-014597-66vd2mdu 2055 2 without without IN cord-014597-66vd2mdu 2055 3 using use VBG cord-014597-66vd2mdu 2055 4 the the DT cord-014597-66vd2mdu 2055 5 CRISPR/ CRISPR/ NNP cord-014597-66vd2mdu 2055 6 Cas9 Cas9 NNP cord-014597-66vd2mdu 2055 7 system system NN cord-014597-66vd2mdu 2055 8 was be VBD cord-014597-66vd2mdu 2055 9 also also RB cord-014597-66vd2mdu 2055 10 performed perform VBN cord-014597-66vd2mdu 2055 11 . . . cord-014597-66vd2mdu 2056 1 These these DT cord-014597-66vd2mdu 2056 2 cell cell NN cord-014597-66vd2mdu 2056 3 pools pool NNS cord-014597-66vd2mdu 2056 4 were be VBD cord-014597-66vd2mdu 2056 5 cultivated cultivate VBN cord-014597-66vd2mdu 2056 6 for for IN cord-014597-66vd2mdu 2056 7 six six CD cord-014597-66vd2mdu 2056 8 days day NNS cord-014597-66vd2mdu 2056 9 with with IN cord-014597-66vd2mdu 2056 10 serum serum NN cord-014597-66vd2mdu 2056 11 - - HYPH cord-014597-66vd2mdu 2056 12 supplemented supplement VBN cord-014597-66vd2mdu 2056 13 medium medium NN cord-014597-66vd2mdu 2056 14 , , , cord-014597-66vd2mdu 2056 15 and and CC cord-014597-66vd2mdu 2056 16 their -PRON- PRP$ cord-014597-66vd2mdu 2056 17 levels level NNS cord-014597-66vd2mdu 2056 18 of of IN cord-014597-66vd2mdu 2056 19 antibody antibody NN cord-014597-66vd2mdu 2056 20 productivity productivity NN cord-014597-66vd2mdu 2056 21 were be VBD cord-014597-66vd2mdu 2056 22 evaluated evaluate VBN cord-014597-66vd2mdu 2056 23 by by IN cord-014597-66vd2mdu 2056 24 ELISA ELISA NNP cord-014597-66vd2mdu 2056 25 . . . cord-014597-66vd2mdu 2057 1 Copy copy JJ cord-014597-66vd2mdu 2057 2 number number NN cord-014597-66vd2mdu 2057 3 analysis analysis NN cord-014597-66vd2mdu 2057 4 was be VBD cord-014597-66vd2mdu 2057 5 also also RB cord-014597-66vd2mdu 2057 6 performed perform VBN cord-014597-66vd2mdu 2057 7 using use VBG cord-014597-66vd2mdu 2057 8 real real JJ cord-014597-66vd2mdu 2057 9 - - HYPH cord-014597-66vd2mdu 2057 10 time time NN cord-014597-66vd2mdu 2057 11 PCR PCR NNP cord-014597-66vd2mdu 2057 12 . . . cord-014597-66vd2mdu 2058 1 Results result NNS cord-014597-66vd2mdu 2058 2 and and CC cord-014597-66vd2mdu 2058 3 discussion discussion NN cord-014597-66vd2mdu 2058 4 Construction construction NN cord-014597-66vd2mdu 2058 5 of of IN cord-014597-66vd2mdu 2058 6 gene gene NN cord-014597-66vd2mdu 2058 7 map map NN cord-014597-66vd2mdu 2058 8 of of IN cord-014597-66vd2mdu 2058 9 chromosome chromosome NN cord-014597-66vd2mdu 2058 10 1 1 CD cord-014597-66vd2mdu 2058 11 : : : cord-014597-66vd2mdu 2059 1 Eighty eighty CD cord-014597-66vd2mdu 2059 2 - - HYPH cord-014597-66vd2mdu 2059 3 three three CD cord-014597-66vd2mdu 2059 4 BAC BAC NNP cord-014597-66vd2mdu 2059 5 clones clone NNS cord-014597-66vd2mdu 2059 6 were be VBD cord-014597-66vd2mdu 2059 7 mapped map VBN cord-014597-66vd2mdu 2059 8 onto onto IN cord-014597-66vd2mdu 2059 9 chromosomes chromosome NNS cord-014597-66vd2mdu 2059 10 A a NN cord-014597-66vd2mdu 2059 11 and and CC cord-014597-66vd2mdu 2059 12 B b NN cord-014597-66vd2mdu 2059 13 ( ( -LRB- cord-014597-66vd2mdu 2059 14 each each DT cord-014597-66vd2mdu 2059 15 clone clone NN cord-014597-66vd2mdu 2059 16 contained contain VBD cord-014597-66vd2mdu 2059 17 100 100 CD cord-014597-66vd2mdu 2059 18 - - SYM cord-014597-66vd2mdu 2059 19 150 150 CD cord-014597-66vd2mdu 2059 20 kb kb NNS cord-014597-66vd2mdu 2059 21 of of IN cord-014597-66vd2mdu 2059 22 the the DT cord-014597-66vd2mdu 2059 23 CHO CHO NNP cord-014597-66vd2mdu 2059 24 genome genome NN cord-014597-66vd2mdu 2059 25 sequence sequence NN cord-014597-66vd2mdu 2059 26 ) ) -RRB- cord-014597-66vd2mdu 2059 27 . . . cord-014597-66vd2mdu 2060 1 As as IN cord-014597-66vd2mdu 2060 2 a a DT cord-014597-66vd2mdu 2060 3 result result NN cord-014597-66vd2mdu 2060 4 of of IN cord-014597-66vd2mdu 2060 5 annotations annotation NNS cord-014597-66vd2mdu 2060 6 of of IN cord-014597-66vd2mdu 2060 7 83 83 CD cord-014597-66vd2mdu 2060 8 BAC BAC NNP cord-014597-66vd2mdu 2060 9 clone clone NN cord-014597-66vd2mdu 2060 10 sequences sequence NNS cord-014597-66vd2mdu 2060 11 , , , cord-014597-66vd2mdu 2060 12 91 91 CD cord-014597-66vd2mdu 2060 13 genes gene NNS cord-014597-66vd2mdu 2060 14 were be VBD cord-014597-66vd2mdu 2060 15 mapped map VBN cord-014597-66vd2mdu 2060 16 on on IN cord-014597-66vd2mdu 2060 17 chromosome chromosome NN cord-014597-66vd2mdu 2060 18 1 1 CD cord-014597-66vd2mdu 2060 19 . . . cord-014597-66vd2mdu 2061 1 Investigation investigation NN cord-014597-66vd2mdu 2061 2 of of IN cord-014597-66vd2mdu 2061 3 the the DT cord-014597-66vd2mdu 2061 4 differences difference NNS cord-014597-66vd2mdu 2061 5 of of IN cord-014597-66vd2mdu 2061 6 productivity productivity NN cord-014597-66vd2mdu 2061 7 among among IN cord-014597-66vd2mdu 2061 8 antibodyproducing antibodyproduce VBG cord-014597-66vd2mdu 2061 9 cells cell NNS cord-014597-66vd2mdu 2061 10 that that WDT cord-014597-66vd2mdu 2061 11 were be VBD cord-014597-66vd2mdu 2061 12 constructed construct VBN cord-014597-66vd2mdu 2061 13 by by IN cord-014597-66vd2mdu 2061 14 chromosome chromosome NN cord-014597-66vd2mdu 2061 15 1 1 CD cord-014597-66vd2mdu 2061 16 targeting targeting NN cord-014597-66vd2mdu 2061 17 and/or and/or CC cord-014597-66vd2mdu 2061 18 random random JJ cord-014597-66vd2mdu 2061 19 integration integration NN cord-014597-66vd2mdu 2061 20 : : : cord-014597-66vd2mdu 2061 21 Cell cell NN cord-014597-66vd2mdu 2061 22 growth growth NN cord-014597-66vd2mdu 2061 23 was be VBD cord-014597-66vd2mdu 2061 24 not not RB cord-014597-66vd2mdu 2061 25 affected affect VBN cord-014597-66vd2mdu 2061 26 by by IN cord-014597-66vd2mdu 2061 27 the the DT cord-014597-66vd2mdu 2061 28 gene gene NN cord-014597-66vd2mdu 2061 29 targeting target VBG cord-014597-66vd2mdu 2061 30 site site NN cord-014597-66vd2mdu 2061 31 . . . cord-014597-66vd2mdu 2062 1 The the DT cord-014597-66vd2mdu 2062 2 specific specific JJ cord-014597-66vd2mdu 2062 3 production production NN cord-014597-66vd2mdu 2062 4 rates rate NNS cord-014597-66vd2mdu 2062 5 of of IN cord-014597-66vd2mdu 2062 6 antibodyproducing antibodyproduce VBG cord-014597-66vd2mdu 2062 7 cell cell NN cord-014597-66vd2mdu 2062 8 pools pool NNS cord-014597-66vd2mdu 2062 9 constructed construct VBN cord-014597-66vd2mdu 2062 10 by by IN cord-014597-66vd2mdu 2062 11 gene gene NN cord-014597-66vd2mdu 2062 12 targeting targeting NN cord-014597-66vd2mdu 2062 13 of of IN cord-014597-66vd2mdu 2062 14 chromosome chromosome NN cord-014597-66vd2mdu 2062 15 1 1 CD cord-014597-66vd2mdu 2062 16 were be VBD cord-014597-66vd2mdu 2062 17 higher high JJR cord-014597-66vd2mdu 2062 18 than than IN cord-014597-66vd2mdu 2062 19 those those DT cord-014597-66vd2mdu 2062 20 of of IN cord-014597-66vd2mdu 2062 21 the the DT cord-014597-66vd2mdu 2062 22 cell cell NN cord-014597-66vd2mdu 2062 23 pool pool NN cord-014597-66vd2mdu 2062 24 constructed construct VBN cord-014597-66vd2mdu 2062 25 by by IN cord-014597-66vd2mdu 2062 26 random random JJ cord-014597-66vd2mdu 2062 27 integration integration NN cord-014597-66vd2mdu 2062 28 . . . cord-014597-66vd2mdu 2063 1 All all DT cord-014597-66vd2mdu 2063 2 cell cell NN cord-014597-66vd2mdu 2063 3 pools pool NNS cord-014597-66vd2mdu 2063 4 constructed construct VBN cord-014597-66vd2mdu 2063 5 by by IN cord-014597-66vd2mdu 2063 6 gene gene NN cord-014597-66vd2mdu 2063 7 targeting targeting NN cord-014597-66vd2mdu 2063 8 showed show VBD cord-014597-66vd2mdu 2063 9 lower low JJR cord-014597-66vd2mdu 2063 10 copy copy NN cord-014597-66vd2mdu 2063 11 numbers number NNS cord-014597-66vd2mdu 2063 12 of of IN cord-014597-66vd2mdu 2063 13 heavy heavy JJ cord-014597-66vd2mdu 2063 14 chain chain NN cord-014597-66vd2mdu 2063 15 and and CC cord-014597-66vd2mdu 2063 16 light light JJ cord-014597-66vd2mdu 2063 17 chain chain NN cord-014597-66vd2mdu 2063 18 in in IN cord-014597-66vd2mdu 2063 19 genomic genomic JJ cord-014597-66vd2mdu 2063 20 DNA dna NN cord-014597-66vd2mdu 2063 21 than than IN cord-014597-66vd2mdu 2063 22 those those DT cord-014597-66vd2mdu 2063 23 in in IN cord-014597-66vd2mdu 2063 24 the the DT cord-014597-66vd2mdu 2063 25 cell cell NN cord-014597-66vd2mdu 2063 26 pool pool NN cord-014597-66vd2mdu 2063 27 constructed construct VBN cord-014597-66vd2mdu 2063 28 by by IN cord-014597-66vd2mdu 2063 29 random random JJ cord-014597-66vd2mdu 2063 30 integration integration NN cord-014597-66vd2mdu 2063 31 , , , cord-014597-66vd2mdu 2063 32 despite despite IN cord-014597-66vd2mdu 2063 33 showing show VBG cord-014597-66vd2mdu 2063 34 high high JJ cord-014597-66vd2mdu 2063 35 productivity productivity NN cord-014597-66vd2mdu 2063 36 . . . cord-014597-66vd2mdu 2064 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2064 2 results result NNS cord-014597-66vd2mdu 2064 3 indicate indicate VBP cord-014597-66vd2mdu 2064 4 that that IN cord-014597-66vd2mdu 2064 5 high high JJ cord-014597-66vd2mdu 2064 6 productivity productivity NN cord-014597-66vd2mdu 2064 7 of of IN cord-014597-66vd2mdu 2064 8 the the DT cord-014597-66vd2mdu 2064 9 cells cell NNS cord-014597-66vd2mdu 2064 10 constructed construct VBN cord-014597-66vd2mdu 2064 11 by by IN cord-014597-66vd2mdu 2064 12 gene gene NN cord-014597-66vd2mdu 2064 13 targeting targeting NN cord-014597-66vd2mdu 2064 14 of of IN cord-014597-66vd2mdu 2064 15 chromosome chromosome NN cord-014597-66vd2mdu 2064 16 1 1 CD cord-014597-66vd2mdu 2064 17 does do VBZ cord-014597-66vd2mdu 2064 18 not not RB cord-014597-66vd2mdu 2064 19 depend depend VB cord-014597-66vd2mdu 2064 20 on on IN cord-014597-66vd2mdu 2064 21 the the DT cord-014597-66vd2mdu 2064 22 increase increase NN cord-014597-66vd2mdu 2064 23 of of IN cord-014597-66vd2mdu 2064 24 the the DT cord-014597-66vd2mdu 2064 25 antibody antibody NN cord-014597-66vd2mdu 2064 26 copy copy NN cord-014597-66vd2mdu 2064 27 number number NN cord-014597-66vd2mdu 2064 28 , , , cord-014597-66vd2mdu 2064 29 and and CC cord-014597-66vd2mdu 2064 30 that that IN cord-014597-66vd2mdu 2064 31 the the DT cord-014597-66vd2mdu 2064 32 environments environment NNS cord-014597-66vd2mdu 2064 33 around around IN cord-014597-66vd2mdu 2064 34 these these DT cord-014597-66vd2mdu 2064 35 target target NN cord-014597-66vd2mdu 2064 36 regions region NNS cord-014597-66vd2mdu 2064 37 are be VBP cord-014597-66vd2mdu 2064 38 suitable suitable JJ cord-014597-66vd2mdu 2064 39 for for IN cord-014597-66vd2mdu 2064 40 exogenous exogenous JJ cord-014597-66vd2mdu 2064 41 gene gene NN cord-014597-66vd2mdu 2064 42 expression expression NN cord-014597-66vd2mdu 2064 43 . . . cord-014597-66vd2mdu 2065 1 The the DT cord-014597-66vd2mdu 2065 2 approach approach NN cord-014597-66vd2mdu 2065 3 of of IN cord-014597-66vd2mdu 2065 4 using use VBG cord-014597-66vd2mdu 2065 5 gene gene NN cord-014597-66vd2mdu 2065 6 targeting target VBG cord-014597-66vd2mdu 2065 7 to to IN cord-014597-66vd2mdu 2065 8 chromosome chromosome NN cord-014597-66vd2mdu 2065 9 1 1 CD cord-014597-66vd2mdu 2065 10 may may MD cord-014597-66vd2mdu 2065 11 be be VB cord-014597-66vd2mdu 2065 12 promising promise VBG cord-014597-66vd2mdu 2065 13 for for IN cord-014597-66vd2mdu 2065 14 constructing construct VBG cord-014597-66vd2mdu 2065 15 antibodyproducing antibodyproduce VBG cord-014597-66vd2mdu 2065 16 cells cell NNS cord-014597-66vd2mdu 2065 17 . . . cord-014597-66vd2mdu 2066 1 Retroviral retroviral NN cord-014597-66vd2mdu 2066 2 vectors vector NNS cord-014597-66vd2mdu 2066 3 have have VBP cord-014597-66vd2mdu 2066 4 been be VBN cord-014597-66vd2mdu 2066 5 widely widely RB cord-014597-66vd2mdu 2066 6 used use VBN cord-014597-66vd2mdu 2066 7 as as IN cord-014597-66vd2mdu 2066 8 gene gene NN cord-014597-66vd2mdu 2066 9 delivery delivery NN cord-014597-66vd2mdu 2066 10 tools tool NNS cord-014597-66vd2mdu 2066 11 in in IN cord-014597-66vd2mdu 2066 12 various various JJ cord-014597-66vd2mdu 2066 13 biotechnology biotechnology NN cord-014597-66vd2mdu 2066 14 fields field NNS cord-014597-66vd2mdu 2066 15 . . . cord-014597-66vd2mdu 2067 1 However however RB cord-014597-66vd2mdu 2067 2 , , , cord-014597-66vd2mdu 2067 3 the the DT cord-014597-66vd2mdu 2067 4 random random JJ cord-014597-66vd2mdu 2067 5 integration integration NN cord-014597-66vd2mdu 2067 6 feature feature NN cord-014597-66vd2mdu 2067 7 of of IN cord-014597-66vd2mdu 2067 8 retroviral retroviral JJ cord-014597-66vd2mdu 2067 9 vectors vector NNS cord-014597-66vd2mdu 2067 10 seems seem VBZ cord-014597-66vd2mdu 2067 11 to to TO cord-014597-66vd2mdu 2067 12 cause cause VB cord-014597-66vd2mdu 2067 13 problems problem NNS cord-014597-66vd2mdu 2067 14 such such JJ cord-014597-66vd2mdu 2067 15 as as IN cord-014597-66vd2mdu 2067 16 insertional insertional JJ cord-014597-66vd2mdu 2067 17 mutagenesis mutagenesis NN cord-014597-66vd2mdu 2067 18 and and CC cord-014597-66vd2mdu 2067 19 gene gene NN cord-014597-66vd2mdu 2067 20 silencing silencing NN cord-014597-66vd2mdu 2067 21 . . . cord-014597-66vd2mdu 2068 1 We -PRON- PRP cord-014597-66vd2mdu 2068 2 previously previously RB cord-014597-66vd2mdu 2068 3 demonstrated demonstrate VBD cord-014597-66vd2mdu 2068 4 Cre Cre NNP cord-014597-66vd2mdu 2068 5 - - HYPH cord-014597-66vd2mdu 2068 6 mediated mediate VBN cord-014597-66vd2mdu 2068 7 retroviral retroviral NN cord-014597-66vd2mdu 2068 8 transgene transgene NN cord-014597-66vd2mdu 2068 9 insertion insertion NN cord-014597-66vd2mdu 2068 10 into into IN cord-014597-66vd2mdu 2068 11 a a DT cord-014597-66vd2mdu 2068 12 pre pre JJ cord-014597-66vd2mdu 2068 13 - - JJ cord-014597-66vd2mdu 2068 14 determined determined JJ cord-014597-66vd2mdu 2068 15 site site NN cord-014597-66vd2mdu 2068 16 of of IN cord-014597-66vd2mdu 2068 17 the the DT cord-014597-66vd2mdu 2068 18 founder founder NN cord-014597-66vd2mdu 2068 19 cells cell NNS cord-014597-66vd2mdu 2068 20 using use VBG cord-014597-66vd2mdu 2068 21 integrasedefective integrasedefective JJ cord-014597-66vd2mdu 2068 22 retroviral retroviral NN cord-014597-66vd2mdu 2068 23 vectors vector NNS cord-014597-66vd2mdu 2068 24 ( ( -LRB- cord-014597-66vd2mdu 2068 25 IDRVs IDRVs NNP cord-014597-66vd2mdu 2068 26 ) ) -RRB- cord-014597-66vd2mdu 2068 27 , , , cord-014597-66vd2mdu 2068 28 where where WRB cord-014597-66vd2mdu 2068 29 a a DT cord-014597-66vd2mdu 2068 30 Cre cre JJ cord-014597-66vd2mdu 2068 31 expression expression NN cord-014597-66vd2mdu 2068 32 plasmid plasmid NN cord-014597-66vd2mdu 2068 33 was be VBD cord-014597-66vd2mdu 2068 34 transfected transfecte VBN cord-014597-66vd2mdu 2068 35 into into IN cord-014597-66vd2mdu 2068 36 the the DT cord-014597-66vd2mdu 2068 37 cells cell NNS cord-014597-66vd2mdu 2068 38 prior prior RB cord-014597-66vd2mdu 2068 39 to to IN cord-014597-66vd2mdu 2068 40 retroviral retroviral JJ cord-014597-66vd2mdu 2068 41 transduction transduction NN cord-014597-66vd2mdu 2068 42 [ [ -LRB- cord-014597-66vd2mdu 2068 43 1 1 CD cord-014597-66vd2mdu 2068 44 ] ] -RRB- cord-014597-66vd2mdu 2068 45 . . . cord-014597-66vd2mdu 2069 1 Recently recently RB cord-014597-66vd2mdu 2069 2 , , , cord-014597-66vd2mdu 2069 3 we -PRON- PRP cord-014597-66vd2mdu 2069 4 reported report VBD cord-014597-66vd2mdu 2069 5 novel novel JJ cord-014597-66vd2mdu 2069 6 hybrid hybrid NN cord-014597-66vd2mdu 2069 7 IDRVs idrv NNS cord-014597-66vd2mdu 2069 8 ( ( -LRB- cord-014597-66vd2mdu 2069 9 Cre Cre NNP cord-014597-66vd2mdu 2069 10 - - HYPH cord-014597-66vd2mdu 2069 11 IDRVs IDRVs NNP cord-014597-66vd2mdu 2069 12 ) ) -RRB- cord-014597-66vd2mdu 2070 1 incorporating incorporate VBG cord-014597-66vd2mdu 2070 2 bioactive bioactive JJ cord-014597-66vd2mdu 2070 3 Cre Cre NNP cord-014597-66vd2mdu 2070 4 recombinase recombinase NN cord-014597-66vd2mdu 2070 5 protein protein NN cord-014597-66vd2mdu 2070 6 , , , cord-014597-66vd2mdu 2070 7 and and CC cord-014597-66vd2mdu 2070 8 validated validate VBD cord-014597-66vd2mdu 2070 9 site site NN cord-014597-66vd2mdu 2070 10 - - HYPH cord-014597-66vd2mdu 2070 11 specific specific JJ cord-014597-66vd2mdu 2070 12 gene gene NN cord-014597-66vd2mdu 2070 13 integration integration NN cord-014597-66vd2mdu 2070 14 of of IN cord-014597-66vd2mdu 2070 15 an an DT cord-014597-66vd2mdu 2070 16 scFv scFv NNP cord-014597-66vd2mdu 2070 17 - - HYPH cord-014597-66vd2mdu 2070 18 Fc Fc NNP cord-014597-66vd2mdu 2070 19 antibody antibody NN cord-014597-66vd2mdu 2070 20 expression expression NN cord-014597-66vd2mdu 2070 21 unit unit NN cord-014597-66vd2mdu 2070 22 into into IN cord-014597-66vd2mdu 2070 23 the the DT cord-014597-66vd2mdu 2070 24 Chinese chinese JJ cord-014597-66vd2mdu 2070 25 hamster hamster NN cord-014597-66vd2mdu 2070 26 ovary ovary NN cord-014597-66vd2mdu 2070 27 ( ( -LRB- cord-014597-66vd2mdu 2070 28 CHO CHO NNP cord-014597-66vd2mdu 2070 29 ) ) -RRB- cord-014597-66vd2mdu 2070 30 cell cell NN cord-014597-66vd2mdu 2070 31 genome genome NN cord-014597-66vd2mdu 2070 32 [ [ -LRB- cord-014597-66vd2mdu 2070 33 2 2 CD cord-014597-66vd2mdu 2070 34 ] ] -RRB- cord-014597-66vd2mdu 2070 35 . . . cord-014597-66vd2mdu 2071 1 We -PRON- PRP cord-014597-66vd2mdu 2071 2 also also RB cord-014597-66vd2mdu 2071 3 developed develop VBD cord-014597-66vd2mdu 2071 4 an an DT cord-014597-66vd2mdu 2071 5 accumulative accumulative JJ cord-014597-66vd2mdu 2071 6 site site NN cord-014597-66vd2mdu 2071 7 - - HYPH cord-014597-66vd2mdu 2071 8 specific specific JJ cord-014597-66vd2mdu 2071 9 gene gene NN cord-014597-66vd2mdu 2071 10 integration integration NN cord-014597-66vd2mdu 2071 11 system system NN cord-014597-66vd2mdu 2071 12 , , , cord-014597-66vd2mdu 2071 13 which which WDT cord-014597-66vd2mdu 2071 14 enables enable VBZ cord-014597-66vd2mdu 2071 15 repeated repeat VBN cord-014597-66vd2mdu 2071 16 integration integration NN cord-014597-66vd2mdu 2071 17 of of IN cord-014597-66vd2mdu 2071 18 multiple multiple JJ cord-014597-66vd2mdu 2071 19 transgenes transgene NNS cord-014597-66vd2mdu 2071 20 into into IN cord-014597-66vd2mdu 2071 21 a a DT cord-014597-66vd2mdu 2071 22 pre pre JJ cord-014597-66vd2mdu 2071 23 - - JJ cord-014597-66vd2mdu 2071 24 determined determined JJ cord-014597-66vd2mdu 2071 25 locus locus NN cord-014597-66vd2mdu 2071 26 of of IN cord-014597-66vd2mdu 2071 27 the the DT cord-014597-66vd2mdu 2071 28 cell cell NN cord-014597-66vd2mdu 2071 29 genome genome NN cord-014597-66vd2mdu 2071 30 [ [ -LRB- cord-014597-66vd2mdu 2071 31 3 3 CD cord-014597-66vd2mdu 2071 32 ] ] -RRB- cord-014597-66vd2mdu 2071 33 . . . cord-014597-66vd2mdu 2072 1 Here here RB cord-014597-66vd2mdu 2072 2 , , , cord-014597-66vd2mdu 2072 3 we -PRON- PRP cord-014597-66vd2mdu 2072 4 attempted attempt VBD cord-014597-66vd2mdu 2072 5 repeated repeated JJ cord-014597-66vd2mdu 2072 6 integration integration NN cord-014597-66vd2mdu 2072 7 of of IN cord-014597-66vd2mdu 2072 8 transgenes transgene NNS cord-014597-66vd2mdu 2072 9 using use VBG cord-014597-66vd2mdu 2072 10 Cre Cre NNP cord-014597-66vd2mdu 2072 11 - - HYPH cord-014597-66vd2mdu 2072 12 IDRVs IDRVs NNP cord-014597-66vd2mdu 2072 13 . . . cord-014597-66vd2mdu 2073 1 A a DT cord-014597-66vd2mdu 2073 2 viral viral JJ cord-014597-66vd2mdu 2073 3 vector vector NN cord-014597-66vd2mdu 2073 4 plasmid plasmid NN cord-014597-66vd2mdu 2073 5 ( ( -LRB- cord-014597-66vd2mdu 2073 6 pQMSCV pQMSCV NNP cord-014597-66vd2mdu 2073 7 / / SYM cord-014597-66vd2mdu 2073 8 HD[scFv HD[scFv NNP cord-014597-66vd2mdu 2073 9 - - HYPH cord-014597-66vd2mdu 2073 10 Fc Fc NNP cord-014597-66vd2mdu 2073 11 ] ] -RRB- cord-014597-66vd2mdu 2073 12 ) ) -RRB- cord-014597-66vd2mdu 2074 1 encoding encode VBG cord-014597-66vd2mdu 2074 2 reporter reporter NN cord-014597-66vd2mdu 2074 3 genes gene NNS cord-014597-66vd2mdu 2074 4 and and CC cord-014597-66vd2mdu 2074 5 an an DT cord-014597-66vd2mdu 2074 6 scFv scFv NNP cord-014597-66vd2mdu 2074 7 - - HYPH cord-014597-66vd2mdu 2074 8 Fc Fc NNP cord-014597-66vd2mdu 2074 9 expression expression NN cord-014597-66vd2mdu 2074 10 unit unit NN cord-014597-66vd2mdu 2074 11 flanked flank VBN cord-014597-66vd2mdu 2074 12 with with IN cord-014597-66vd2mdu 2074 13 wild wild JJ cord-014597-66vd2mdu 2074 14 - - HYPH cord-014597-66vd2mdu 2074 15 type type NN cord-014597-66vd2mdu 2074 16 and and CC cord-014597-66vd2mdu 2074 17 mutant mutant JJ cord-014597-66vd2mdu 2074 18 loxPs loxp NNS cord-014597-66vd2mdu 2074 19 was be VBD cord-014597-66vd2mdu 2074 20 constructed construct VBN cord-014597-66vd2mdu 2074 21 for for IN cord-014597-66vd2mdu 2074 22 the the DT cord-014597-66vd2mdu 2074 23 production production NN cord-014597-66vd2mdu 2074 24 of of IN cord-014597-66vd2mdu 2074 25 IDRVs idrvs PRP cord-014597-66vd2mdu 2074 26 . . . cord-014597-66vd2mdu 2075 1 Cre Cre NNP cord-014597-66vd2mdu 2075 2 - - HYPH cord-014597-66vd2mdu 2075 3 IDRVs idrv NNS cord-014597-66vd2mdu 2075 4 were be VBD cord-014597-66vd2mdu 2075 5 produced produce VBN cord-014597-66vd2mdu 2075 6 described describe VBN cord-014597-66vd2mdu 2075 7 previously previously RB cord-014597-66vd2mdu 2075 8 [ [ -LRB- cord-014597-66vd2mdu 2075 9 2 2 CD cord-014597-66vd2mdu 2075 10 ] ] -RRB- cord-014597-66vd2mdu 2075 11 . . . cord-014597-66vd2mdu 2076 1 Results result NNS cord-014597-66vd2mdu 2076 2 and and CC cord-014597-66vd2mdu 2076 3 discussion discussion NN cord-014597-66vd2mdu 2076 4 Figure figure NN cord-014597-66vd2mdu 2076 5 1a 1a NN cord-014597-66vd2mdu 2076 6 shows show VBZ cord-014597-66vd2mdu 2076 7 a a DT cord-014597-66vd2mdu 2076 8 schematic schematic JJ cord-014597-66vd2mdu 2076 9 drawing drawing NN cord-014597-66vd2mdu 2076 10 of of IN cord-014597-66vd2mdu 2076 11 each each DT cord-014597-66vd2mdu 2076 12 round round NN cord-014597-66vd2mdu 2076 13 of of IN cord-014597-66vd2mdu 2076 14 targeted target VBN cord-014597-66vd2mdu 2076 15 transgene transgene NN cord-014597-66vd2mdu 2076 16 integration integration NN cord-014597-66vd2mdu 2076 17 using use VBG cord-014597-66vd2mdu 2076 18 Cre Cre NNP cord-014597-66vd2mdu 2076 19 - - HYPH cord-014597-66vd2mdu 2076 20 IDRVs IDRVs NNP cord-014597-66vd2mdu 2076 21 harboring harbor VBG cord-014597-66vd2mdu 2076 22 an an DT cord-014597-66vd2mdu 2076 23 scFv scFv NNP cord-014597-66vd2mdu 2076 24 - - HYPH cord-014597-66vd2mdu 2076 25 Fc Fc NNP cord-014597-66vd2mdu 2076 26 expression expression NN cord-014597-66vd2mdu 2076 27 unit unit NN cord-014597-66vd2mdu 2076 28 . . . cord-014597-66vd2mdu 2077 1 ( ( -LRB- cord-014597-66vd2mdu 2077 2 Fig Fig NNP cord-014597-66vd2mdu 2077 3 . . . cord-014597-66vd2mdu 2077 4 1b 1b CD cord-014597-66vd2mdu 2077 5 ) ) -RRB- cord-014597-66vd2mdu 2077 6 . . . cord-014597-66vd2mdu 2078 1 Genomic genomic JJ cord-014597-66vd2mdu 2078 2 DNA dna NN cord-014597-66vd2mdu 2078 3 extracted extract VBN cord-014597-66vd2mdu 2078 4 from from IN cord-014597-66vd2mdu 2078 5 the the DT cord-014597-66vd2mdu 2078 6 cells cell NNS cord-014597-66vd2mdu 2078 7 were be VBD cord-014597-66vd2mdu 2078 8 subjected subject VBN cord-014597-66vd2mdu 2078 9 to to IN cord-014597-66vd2mdu 2078 10 PCR PCR NNP cord-014597-66vd2mdu 2078 11 using use VBG cord-014597-66vd2mdu 2078 12 specific specific JJ cord-014597-66vd2mdu 2078 13 primer primer NN cord-014597-66vd2mdu 2078 14 pairs pair NNS cord-014597-66vd2mdu 2078 15 α α NN cord-014597-66vd2mdu 2078 16 and and CC cord-014597-66vd2mdu 2078 17 β β NN cord-014597-66vd2mdu 2078 18 , , , cord-014597-66vd2mdu 2078 19 and and CC cord-014597-66vd2mdu 2078 20 γ γ NN cord-014597-66vd2mdu 2078 21 and and CC cord-014597-66vd2mdu 2078 22 δ δ NN cord-014597-66vd2mdu 2078 23 to to TO cord-014597-66vd2mdu 2078 24 confirm confirm VB cord-014597-66vd2mdu 2078 25 site site NN cord-014597-66vd2mdu 2078 26 - - HYPH cord-014597-66vd2mdu 2078 27 specific specific JJ cord-014597-66vd2mdu 2078 28 integration integration NN cord-014597-66vd2mdu 2078 29 . . . cord-014597-66vd2mdu 2079 1 DNA dna NN cord-014597-66vd2mdu 2079 2 fragments fragment NNS cord-014597-66vd2mdu 2079 3 with with IN cord-014597-66vd2mdu 2079 4 expected expect VBN cord-014597-66vd2mdu 2079 5 sizes size NNS cord-014597-66vd2mdu 2079 6 were be VBD cord-014597-66vd2mdu 2079 7 amplified amplify VBN cord-014597-66vd2mdu 2079 8 in in IN cord-014597-66vd2mdu 2079 9 each each DT cord-014597-66vd2mdu 2079 10 cell cell NN cord-014597-66vd2mdu 2079 11 clone clone NN cord-014597-66vd2mdu 2079 12 ( ( -LRB- cord-014597-66vd2mdu 2079 13 Fig Fig NNP cord-014597-66vd2mdu 2079 14 . . . cord-014597-66vd2mdu 2079 15 1c 1c CD cord-014597-66vd2mdu 2079 16 ) ) -RRB- cord-014597-66vd2mdu 2079 17 . . . cord-014597-66vd2mdu 2080 1 These these DT cord-014597-66vd2mdu 2080 2 results result NNS cord-014597-66vd2mdu 2080 3 indicate indicate VBP cord-014597-66vd2mdu 2080 4 that that IN cord-014597-66vd2mdu 2080 5 site site NN cord-014597-66vd2mdu 2080 6 - - HYPH cord-014597-66vd2mdu 2080 7 specific specific JJ cord-014597-66vd2mdu 2080 8 repeated repeat VBN cord-014597-66vd2mdu 2080 9 integration integration NN cord-014597-66vd2mdu 2080 10 was be VBD cord-014597-66vd2mdu 2080 11 achieved achieve VBN cord-014597-66vd2mdu 2080 12 using use VBG cord-014597-66vd2mdu 2080 13 Cre Cre NNP cord-014597-66vd2mdu 2080 14 - - HYPH cord-014597-66vd2mdu 2080 15 IDRVs IDRVs NNP cord-014597-66vd2mdu 2080 16 . . . cord-014597-66vd2mdu 2081 1 In in IN cord-014597-66vd2mdu 2081 2 contrast contrast NN cord-014597-66vd2mdu 2081 3 , , , cord-014597-66vd2mdu 2081 4 scFv scFv NNP cord-014597-66vd2mdu 2081 5 - - HYPH cord-014597-66vd2mdu 2081 6 Fc Fc NNP cord-014597-66vd2mdu 2081 7 productivity productivity NN cord-014597-66vd2mdu 2081 8 in in IN cord-014597-66vd2mdu 2081 9 CHO CHO NNP cord-014597-66vd2mdu 2081 10 / / SYM cord-014597-66vd2mdu 2081 11 HD[scFv HD[scFv NNP cord-014597-66vd2mdu 2081 12 - - HYPH cord-014597-66vd2mdu 2081 13 Fc]×2 Fc]×2 NNP cord-014597-66vd2mdu 2081 14 cells cell NNS cord-014597-66vd2mdu 2081 15 was be VBD cord-014597-66vd2mdu 2081 16 slightly slightly RB cord-014597-66vd2mdu 2081 17 decreased decrease VBN cord-014597-66vd2mdu 2081 18 compared compare VBN cord-014597-66vd2mdu 2081 19 with with IN cord-014597-66vd2mdu 2081 20 that that DT cord-014597-66vd2mdu 2081 21 of of IN cord-014597-66vd2mdu 2081 22 CHO CHO NNP cord-014597-66vd2mdu 2081 23 / / SYM cord-014597-66vd2mdu 2081 24 NE[scFv NE[scFv NNP cord-014597-66vd2mdu 2082 1 -Fc]×1 -Fc]×1 NFP cord-014597-66vd2mdu 2082 2 ( ( -LRB- cord-014597-66vd2mdu 2082 3 data datum NNS cord-014597-66vd2mdu 2082 4 not not RB cord-014597-66vd2mdu 2082 5 shown show VBN cord-014597-66vd2mdu 2082 6 ) ) -RRB- cord-014597-66vd2mdu 2082 7 . . . cord-014597-66vd2mdu 2083 1 Although although IN cord-014597-66vd2mdu 2083 2 the the DT cord-014597-66vd2mdu 2083 3 reason reason NN cord-014597-66vd2mdu 2083 4 remains remain VBZ cord-014597-66vd2mdu 2083 5 unclear unclear JJ cord-014597-66vd2mdu 2083 6 , , , cord-014597-66vd2mdu 2083 7 repeat repeat VB cord-014597-66vd2mdu 2083 8 - - HYPH cord-014597-66vd2mdu 2083 9 induced induce VBN cord-014597-66vd2mdu 2083 10 gene gene NN cord-014597-66vd2mdu 2083 11 silencing silencing NN cord-014597-66vd2mdu 2083 12 might may MD cord-014597-66vd2mdu 2083 13 occur occur VB cord-014597-66vd2mdu 2083 14 due due IN cord-014597-66vd2mdu 2083 15 to to TO cord-014597-66vd2mdu 2083 16 tandem tandem JJ cord-014597-66vd2mdu 2083 17 repeat repeat NN cord-014597-66vd2mdu 2083 18 structure structure NN cord-014597-66vd2mdu 2083 19 of of IN cord-014597-66vd2mdu 2083 20 expression expression NN cord-014597-66vd2mdu 2083 21 units unit NNS cord-014597-66vd2mdu 2083 22 . . . cord-014597-66vd2mdu 2084 1 We -PRON- PRP cord-014597-66vd2mdu 2084 2 reported report VBD cord-014597-66vd2mdu 2084 3 improved improve VBN cord-014597-66vd2mdu 2084 4 recombinant recombinant JJ cord-014597-66vd2mdu 2084 5 antibody antibody NN cord-014597-66vd2mdu 2084 6 production production NN cord-014597-66vd2mdu 2084 7 using use VBG cord-014597-66vd2mdu 2084 8 a a DT cord-014597-66vd2mdu 2084 9 production production NN cord-014597-66vd2mdu 2084 10 enhancer enhancer NN cord-014597-66vd2mdu 2084 11 element element NN cord-014597-66vd2mdu 2084 12 [ [ -LRB- cord-014597-66vd2mdu 2084 13 4 4 CD cord-014597-66vd2mdu 2084 14 ] ] -RRB- cord-014597-66vd2mdu 2084 15 . . . cord-014597-66vd2mdu 2085 1 Such such JJ cord-014597-66vd2mdu 2085 2 a a DT cord-014597-66vd2mdu 2085 3 cis cis JJ cord-014597-66vd2mdu 2085 4 - - HYPH cord-014597-66vd2mdu 2085 5 regulatory regulatory JJ cord-014597-66vd2mdu 2085 6 element element NN cord-014597-66vd2mdu 2085 7 might may MD cord-014597-66vd2mdu 2085 8 be be VB cord-014597-66vd2mdu 2085 9 a a DT cord-014597-66vd2mdu 2085 10 feasible feasible JJ cord-014597-66vd2mdu 2085 11 approach approach NN cord-014597-66vd2mdu 2085 12 to to TO cord-014597-66vd2mdu 2085 13 enhance enhance VB cord-014597-66vd2mdu 2085 14 the the DT cord-014597-66vd2mdu 2085 15 productivity productivity NN cord-014597-66vd2mdu 2085 16 . . . cord-014597-66vd2mdu 2086 1 We -PRON- PRP cord-014597-66vd2mdu 2086 2 demonstrated demonstrate VBD cord-014597-66vd2mdu 2086 3 site site NN cord-014597-66vd2mdu 2086 4 - - HYPH cord-014597-66vd2mdu 2086 5 specific specific JJ cord-014597-66vd2mdu 2086 6 repeated repeat VBN cord-014597-66vd2mdu 2086 7 transgene transgene NN cord-014597-66vd2mdu 2086 8 integration integration NN cord-014597-66vd2mdu 2086 9 into into IN cord-014597-66vd2mdu 2086 10 a a DT cord-014597-66vd2mdu 2086 11 pre pre JJ cord-014597-66vd2mdu 2086 12 - - JJ cord-014597-66vd2mdu 2086 13 determined determined JJ cord-014597-66vd2mdu 2086 14 chromosomal chromosomal JJ cord-014597-66vd2mdu 2086 15 locus locus NN cord-014597-66vd2mdu 2086 16 using use VBG cord-014597-66vd2mdu 2086 17 Cre Cre NNP cord-014597-66vd2mdu 2086 18 - - HYPH cord-014597-66vd2mdu 2086 19 IDRVs IDRVs NNP cord-014597-66vd2mdu 2086 20 for for IN cord-014597-66vd2mdu 2086 21 the the DT cord-014597-66vd2mdu 2086 22 production production NN cord-014597-66vd2mdu 2086 23 of of IN cord-014597-66vd2mdu 2086 24 an an DT cord-014597-66vd2mdu 2086 25 scFv scFv NNP cord-014597-66vd2mdu 2086 26 - - HYPH cord-014597-66vd2mdu 2086 27 Fc Fc NNP cord-014597-66vd2mdu 2086 28 antibody antibody NN cord-014597-66vd2mdu 2086 29 . . . cord-014597-66vd2mdu 2087 1 If if IN cord-014597-66vd2mdu 2087 2 lipids lipid NNS cord-014597-66vd2mdu 2087 3 role role NN cord-014597-66vd2mdu 2087 4 in in IN cord-014597-66vd2mdu 2087 5 the the DT cord-014597-66vd2mdu 2087 6 cell cell NN cord-014597-66vd2mdu 2087 7 have have VBP cord-014597-66vd2mdu 2087 8 been be VBN cord-014597-66vd2mdu 2087 9 reduced reduce VBN cord-014597-66vd2mdu 2087 10 for for IN cord-014597-66vd2mdu 2087 11 a a DT cord-014597-66vd2mdu 2087 12 long long JJ cord-014597-66vd2mdu 2087 13 time time NN cord-014597-66vd2mdu 2087 14 to to IN cord-014597-66vd2mdu 2087 15 cell cell NN cord-014597-66vd2mdu 2087 16 membrane membrane NN cord-014597-66vd2mdu 2087 17 formation formation NN cord-014597-66vd2mdu 2087 18 , , , cord-014597-66vd2mdu 2087 19 it -PRON- PRP cord-014597-66vd2mdu 2087 20 is be VBZ cord-014597-66vd2mdu 2087 21 now now RB cord-014597-66vd2mdu 2087 22 understood understand VBN cord-014597-66vd2mdu 2087 23 that that IN cord-014597-66vd2mdu 2087 24 lipids lipid NNS cord-014597-66vd2mdu 2087 25 plays play VBZ cord-014597-66vd2mdu 2087 26 also also RB cord-014597-66vd2mdu 2087 27 a a DT cord-014597-66vd2mdu 2087 28 role role NN cord-014597-66vd2mdu 2087 29 into into IN cord-014597-66vd2mdu 2087 30 energy energy NN cord-014597-66vd2mdu 2087 31 metabolism metabolism NN cord-014597-66vd2mdu 2087 32 , , , cord-014597-66vd2mdu 2087 33 vesicular vesicular JJ cord-014597-66vd2mdu 2087 34 transport transport NN cord-014597-66vd2mdu 2087 35 , , , cord-014597-66vd2mdu 2087 36 membrane membrane NN cord-014597-66vd2mdu 2087 37 structure structure NN cord-014597-66vd2mdu 2087 38 , , , cord-014597-66vd2mdu 2087 39 dynamics dynamic NNS cord-014597-66vd2mdu 2087 40 and and CC cord-014597-66vd2mdu 2087 41 signaling signaling NN cord-014597-66vd2mdu 2087 42 . . . cord-014597-66vd2mdu 2088 1 However however RB cord-014597-66vd2mdu 2088 2 , , , cord-014597-66vd2mdu 2088 3 the the DT cord-014597-66vd2mdu 2088 4 exact exact JJ cord-014597-66vd2mdu 2088 5 mechanism mechanism NN cord-014597-66vd2mdu 2088 6 of of IN cord-014597-66vd2mdu 2088 7 how how WRB cord-014597-66vd2mdu 2088 8 compositional compositional JJ cord-014597-66vd2mdu 2088 9 complexity complexity NN cord-014597-66vd2mdu 2088 10 affects affect VBZ cord-014597-66vd2mdu 2088 11 cell cell NN cord-014597-66vd2mdu 2088 12 homeostasis homeostasis NN cord-014597-66vd2mdu 2088 13 remains remain VBZ cord-014597-66vd2mdu 2088 14 unclear unclear JJ cord-014597-66vd2mdu 2088 15 . . . cord-014597-66vd2mdu 2089 1 Thanks thank NNS cord-014597-66vd2mdu 2089 2 to to IN cord-014597-66vd2mdu 2089 3 recent recent JJ cord-014597-66vd2mdu 2089 4 advances advance NNS cord-014597-66vd2mdu 2089 5 in in IN cord-014597-66vd2mdu 2089 6 mass mass NN cord-014597-66vd2mdu 2089 7 spectrometry spectrometry NN cord-014597-66vd2mdu 2089 8 , , , cord-014597-66vd2mdu 2089 9 it -PRON- PRP cord-014597-66vd2mdu 2089 10 is be VBZ cord-014597-66vd2mdu 2089 11 now now RB cord-014597-66vd2mdu 2089 12 possible possible JJ cord-014597-66vd2mdu 2089 13 to to TO cord-014597-66vd2mdu 2089 14 study study VB cord-014597-66vd2mdu 2089 15 a a DT cord-014597-66vd2mdu 2089 16 wide wide JJ cord-014597-66vd2mdu 2089 17 range range NN cord-014597-66vd2mdu 2089 18 of of IN cord-014597-66vd2mdu 2089 19 lipids lipid NNS cord-014597-66vd2mdu 2089 20 , , , cord-014597-66vd2mdu 2089 21 providing provide VBG cord-014597-66vd2mdu 2089 22 a a DT cord-014597-66vd2mdu 2089 23 better well JJR cord-014597-66vd2mdu 2089 24 understanding understanding NN cord-014597-66vd2mdu 2089 25 of of IN cord-014597-66vd2mdu 2089 26 lipid lipid NN cord-014597-66vd2mdu 2089 27 homeostasis homeostasis NN cord-014597-66vd2mdu 2089 28 in in IN cord-014597-66vd2mdu 2089 29 high high JJ cord-014597-66vd2mdu 2089 30 performance performance NN cord-014597-66vd2mdu 2089 31 cell cell NN cord-014597-66vd2mdu 2089 32 culture culture NN cord-014597-66vd2mdu 2089 33 processes process NNS cord-014597-66vd2mdu 2089 34 . . . cord-014597-66vd2mdu 2090 1 The the DT cord-014597-66vd2mdu 2090 2 purpose purpose NN cord-014597-66vd2mdu 2090 3 of of IN cord-014597-66vd2mdu 2090 4 this this DT cord-014597-66vd2mdu 2090 5 work work NN cord-014597-66vd2mdu 2090 6 was be VBD cord-014597-66vd2mdu 2090 7 to to TO cord-014597-66vd2mdu 2090 8 develop develop VB cord-014597-66vd2mdu 2090 9 a a DT cord-014597-66vd2mdu 2090 10 robust robust JJ cord-014597-66vd2mdu 2090 11 lipidomics lipidomic NNS cord-014597-66vd2mdu 2090 12 method method NN cord-014597-66vd2mdu 2090 13 applied apply VBN cord-014597-66vd2mdu 2090 14 to to IN cord-014597-66vd2mdu 2090 15 mammalian mammalian JJ cord-014597-66vd2mdu 2090 16 cell cell NN cord-014597-66vd2mdu 2090 17 cultures culture NNS cord-014597-66vd2mdu 2090 18 in in IN cord-014597-66vd2mdu 2090 19 a a DT cord-014597-66vd2mdu 2090 20 three three CD cord-014597-66vd2mdu 2090 21 step step NN cord-014597-66vd2mdu 2090 22 method method NN cord-014597-66vd2mdu 2090 23 : : : cord-014597-66vd2mdu 2090 24 extraction extraction NN cord-014597-66vd2mdu 2090 25 , , , cord-014597-66vd2mdu 2090 26 separation separation NN cord-014597-66vd2mdu 2090 27 and and CC cord-014597-66vd2mdu 2090 28 detection detection NN cord-014597-66vd2mdu 2090 29 ( ( -LRB- cord-014597-66vd2mdu 2090 30 Fig Fig NNP cord-014597-66vd2mdu 2090 31 . . . cord-014597-66vd2mdu 2090 32 1 1 CD cord-014597-66vd2mdu 2090 33 ) ) -RRB- cord-014597-66vd2mdu 2090 34 . . . cord-014597-66vd2mdu 2091 1 Both both DT cord-014597-66vd2mdu 2091 2 Matyash Matyash NNP cord-014597-66vd2mdu 2091 3 [ [ -LRB- cord-014597-66vd2mdu 2091 4 1 1 CD cord-014597-66vd2mdu 2091 5 ] ] -RRB- cord-014597-66vd2mdu 2091 6 and and CC cord-014597-66vd2mdu 2091 7 Folch Folch NNP cord-014597-66vd2mdu 2091 8 [ [ -LRB- cord-014597-66vd2mdu 2091 9 2 2 CD cord-014597-66vd2mdu 2091 10 ] ] -RRB- cord-014597-66vd2mdu 2091 11 extraction extraction NN cord-014597-66vd2mdu 2091 12 method method NN cord-014597-66vd2mdu 2091 13 were be VBD cord-014597-66vd2mdu 2091 14 performed perform VBN cord-014597-66vd2mdu 2091 15 on on IN cord-014597-66vd2mdu 2091 16 our -PRON- PRP$ cord-014597-66vd2mdu 2091 17 cells cell NNS cord-014597-66vd2mdu 2091 18 to to TO cord-014597-66vd2mdu 2091 19 reach reach VB cord-014597-66vd2mdu 2091 20 the the DT cord-014597-66vd2mdu 2091 21 highest high JJS cord-014597-66vd2mdu 2091 22 yield yield NN cord-014597-66vd2mdu 2091 23 . . . cord-014597-66vd2mdu 2092 1 Two two CD cord-014597-66vd2mdu 2092 2 separation separation NN cord-014597-66vd2mdu 2092 3 techniques technique NNS cord-014597-66vd2mdu 2092 4 were be VBD cord-014597-66vd2mdu 2092 5 also also RB cord-014597-66vd2mdu 2092 6 tested test VBN cord-014597-66vd2mdu 2092 7 : : : cord-014597-66vd2mdu 2092 8 hydrophilic hydrophilic JJ cord-014597-66vd2mdu 2092 9 interaction interaction NN cord-014597-66vd2mdu 2092 10 liquid liquid NN cord-014597-66vd2mdu 2092 11 chromatography chromatography NN cord-014597-66vd2mdu 2092 12 ( ( -LRB- cord-014597-66vd2mdu 2092 13 HILIC HILIC NNP cord-014597-66vd2mdu 2092 14 ) ) -RRB- cord-014597-66vd2mdu 2092 15 and and CC cord-014597-66vd2mdu 2092 16 reverse reverse VB cord-014597-66vd2mdu 2092 17 phase phase NN cord-014597-66vd2mdu 2092 18 chromatography chromatography NN cord-014597-66vd2mdu 2092 19 . . . cord-014597-66vd2mdu 2093 1 Finally finally RB cord-014597-66vd2mdu 2093 2 lipid lipid NN cord-014597-66vd2mdu 2093 3 classes class NNS cord-014597-66vd2mdu 2093 4 ' ' POS cord-014597-66vd2mdu 2093 5 identification identification NN cord-014597-66vd2mdu 2093 6 was be VBD cord-014597-66vd2mdu 2093 7 achieved achieve VBN cord-014597-66vd2mdu 2093 8 by by IN cord-014597-66vd2mdu 2093 9 tandem tandem JJ cord-014597-66vd2mdu 2093 10 mass mass NN cord-014597-66vd2mdu 2093 11 spectrometry spectrometry NN cord-014597-66vd2mdu 2093 12 analysis analysis NN cord-014597-66vd2mdu 2093 13 thanks thank NNS cord-014597-66vd2mdu 2093 14 to to IN cord-014597-66vd2mdu 2093 15 structure structure NN cord-014597-66vd2mdu 2093 16 - - HYPH cord-014597-66vd2mdu 2093 17 specific specific JJ cord-014597-66vd2mdu 2093 18 fragmentation fragmentation NN cord-014597-66vd2mdu 2093 19 ions ion NNS cord-014597-66vd2mdu 2093 20 . . . cord-014597-66vd2mdu 2094 1 The the DT cord-014597-66vd2mdu 2094 2 yield yield NN cord-014597-66vd2mdu 2094 3 obtained obtain VBN cord-014597-66vd2mdu 2094 4 with with IN cord-014597-66vd2mdu 2094 5 Matyash Matyash NNP cord-014597-66vd2mdu 2094 6 extraction extraction NN cord-014597-66vd2mdu 2094 7 method method NN cord-014597-66vd2mdu 2094 8 was be VBD cord-014597-66vd2mdu 2094 9 higher high JJR cord-014597-66vd2mdu 2094 10 than than IN cord-014597-66vd2mdu 2094 11 with with IN cord-014597-66vd2mdu 2094 12 Folch Folch NNP cord-014597-66vd2mdu 2094 13 method method NN cord-014597-66vd2mdu 2094 14 for for IN cord-014597-66vd2mdu 2094 15 each each DT cord-014597-66vd2mdu 2094 16 lipid lipid NN cord-014597-66vd2mdu 2094 17 class class NN cord-014597-66vd2mdu 2094 18 tested test VBN cord-014597-66vd2mdu 2094 19 . . . cord-014597-66vd2mdu 2095 1 Besides besides RB cord-014597-66vd2mdu 2095 2 , , , cord-014597-66vd2mdu 2095 3 Matyash Matyash NNP cord-014597-66vd2mdu 2095 4 method method NN cord-014597-66vd2mdu 2095 5 presents present VBZ cord-014597-66vd2mdu 2095 6 also also RB cord-014597-66vd2mdu 2095 7 the the DT cord-014597-66vd2mdu 2095 8 advantage advantage NN cord-014597-66vd2mdu 2095 9 to to TO cord-014597-66vd2mdu 2095 10 be be VB cord-014597-66vd2mdu 2095 11 less less RBR cord-014597-66vd2mdu 2095 12 toxic toxic JJ cord-014597-66vd2mdu 2095 13 and and CC cord-014597-66vd2mdu 2095 14 suitable suitable JJ cord-014597-66vd2mdu 2095 15 for for IN cord-014597-66vd2mdu 2095 16 high high JJ cord-014597-66vd2mdu 2095 17 throughput throughput NN cord-014597-66vd2mdu 2095 18 analysis analysis NN cord-014597-66vd2mdu 2095 19 since since IN cord-014597-66vd2mdu 2095 20 the the DT cord-014597-66vd2mdu 2095 21 organic organic JJ cord-014597-66vd2mdu 2095 22 layer layer NN cord-014597-66vd2mdu 2095 23 is be VBZ cord-014597-66vd2mdu 2095 24 above above IN cord-014597-66vd2mdu 2095 25 the the DT cord-014597-66vd2mdu 2095 26 aqueous aqueous JJ cord-014597-66vd2mdu 2095 27 layer layer NN cord-014597-66vd2mdu 2095 28 . . . cord-014597-66vd2mdu 2096 1 Lipids lipid NNS cord-014597-66vd2mdu 2096 2 separation separation NN cord-014597-66vd2mdu 2096 3 by by IN cord-014597-66vd2mdu 2096 4 HILIC HILIC NNP cord-014597-66vd2mdu 2096 5 is be VBZ cord-014597-66vd2mdu 2096 6 based base VBN cord-014597-66vd2mdu 2096 7 on on IN cord-014597-66vd2mdu 2096 8 their -PRON- PRP$ cord-014597-66vd2mdu 2096 9 polar polar JJ cord-014597-66vd2mdu 2096 10 head head NN cord-014597-66vd2mdu 2096 11 . . . cord-014597-66vd2mdu 2097 1 Since since IN cord-014597-66vd2mdu 2097 2 lipid lipid NN cord-014597-66vd2mdu 2097 3 classes class NNS cord-014597-66vd2mdu 2097 4 are be VBP cord-014597-66vd2mdu 2097 5 defined define VBN cord-014597-66vd2mdu 2097 6 by by IN cord-014597-66vd2mdu 2097 7 polar polar JJ cord-014597-66vd2mdu 2097 8 head head NN cord-014597-66vd2mdu 2097 9 , , , cord-014597-66vd2mdu 2097 10 the the DT cord-014597-66vd2mdu 2097 11 lipids lipid NNS cord-014597-66vd2mdu 2097 12 are be VBP cord-014597-66vd2mdu 2097 13 eluted elute VBN cord-014597-66vd2mdu 2097 14 class class NN cord-014597-66vd2mdu 2097 15 by by IN cord-014597-66vd2mdu 2097 16 class class NN cord-014597-66vd2mdu 2097 17 , , , cord-014597-66vd2mdu 2097 18 making make VBG cord-014597-66vd2mdu 2097 19 their -PRON- PRP$ cord-014597-66vd2mdu 2097 20 identification identification NN cord-014597-66vd2mdu 2097 21 easier easy JJR cord-014597-66vd2mdu 2097 22 . . . cord-014597-66vd2mdu 2098 1 The the DT cord-014597-66vd2mdu 2098 2 separation separation NN cord-014597-66vd2mdu 2098 3 of of IN cord-014597-66vd2mdu 2098 4 lipids lipid NNS cord-014597-66vd2mdu 2098 5 by by IN cord-014597-66vd2mdu 2098 6 reverse reverse JJ cord-014597-66vd2mdu 2098 7 phase phase NN cord-014597-66vd2mdu 2098 8 was be VBD cord-014597-66vd2mdu 2098 9 correct correct JJ cord-014597-66vd2mdu 2098 10 but but CC cord-014597-66vd2mdu 2098 11 the the DT cord-014597-66vd2mdu 2098 12 method method NN cord-014597-66vd2mdu 2098 13 is be VBZ cord-014597-66vd2mdu 2098 14 longer long JJR cord-014597-66vd2mdu 2098 15 and and CC cord-014597-66vd2mdu 2098 16 we -PRON- PRP cord-014597-66vd2mdu 2098 17 observed observe VBD cord-014597-66vd2mdu 2098 18 a a DT cord-014597-66vd2mdu 2098 19 massive massive JJ cord-014597-66vd2mdu 2098 20 carryover carryover NN cord-014597-66vd2mdu 2098 21 of of IN cord-014597-66vd2mdu 2098 22 triglycerides triglyceride NNS cord-014597-66vd2mdu 2098 23 on on IN cord-014597-66vd2mdu 2098 24 the the DT cord-014597-66vd2mdu 2098 25 column column NN cord-014597-66vd2mdu 2098 26 . . . cord-014597-66vd2mdu 2099 1 Finally finally RB cord-014597-66vd2mdu 2099 2 each each DT cord-014597-66vd2mdu 2099 3 lipid lipid NN cord-014597-66vd2mdu 2099 4 class class NN cord-014597-66vd2mdu 2099 5 was be VBD cord-014597-66vd2mdu 2099 6 screened screen VBN cord-014597-66vd2mdu 2099 7 in in IN cord-014597-66vd2mdu 2099 8 MS MS NNP cord-014597-66vd2mdu 2099 9 / / SYM cord-014597-66vd2mdu 2099 10 MS MS NNP cord-014597-66vd2mdu 2099 11 parent parent NN cord-014597-66vd2mdu 2099 12 ion ion NN cord-014597-66vd2mdu 2099 13 mode mode NN cord-014597-66vd2mdu 2099 14 . . . cord-014597-66vd2mdu 2100 1 Target Target NNP cord-014597-66vd2mdu 2100 2 daughter daughter NN cord-014597-66vd2mdu 2100 3 ion ion NN cord-014597-66vd2mdu 2100 4 was be VBD cord-014597-66vd2mdu 2100 5 set set VBN cord-014597-66vd2mdu 2100 6 according accord VBG cord-014597-66vd2mdu 2100 7 to to IN cord-014597-66vd2mdu 2100 8 the the DT cord-014597-66vd2mdu 2100 9 lipid lipid NN cord-014597-66vd2mdu 2100 10 class class NN cord-014597-66vd2mdu 2100 11 structure structure NN cord-014597-66vd2mdu 2100 12 and and CC cord-014597-66vd2mdu 2100 13 fragmentation fragmentation NN cord-014597-66vd2mdu 2100 14 pattern pattern NN cord-014597-66vd2mdu 2100 15 . . . cord-014597-66vd2mdu 2101 1 This this DT cord-014597-66vd2mdu 2101 2 detection detection NN cord-014597-66vd2mdu 2101 3 technique technique NN cord-014597-66vd2mdu 2101 4 enabled enable VBD cord-014597-66vd2mdu 2101 5 the the DT cord-014597-66vd2mdu 2101 6 identification identification NN cord-014597-66vd2mdu 2101 7 of of IN cord-014597-66vd2mdu 2101 8 50 50 CD cord-014597-66vd2mdu 2101 9 different different JJ cord-014597-66vd2mdu 2101 10 lipids lipid NNS cord-014597-66vd2mdu 2101 11 . . . cord-014597-66vd2mdu 2102 1 To to TO cord-014597-66vd2mdu 2102 2 ensure ensure VB cord-014597-66vd2mdu 2102 3 the the DT cord-014597-66vd2mdu 2102 4 absolute absolute JJ cord-014597-66vd2mdu 2102 5 quantification quantification NN cord-014597-66vd2mdu 2102 6 of of IN cord-014597-66vd2mdu 2102 7 the the DT cord-014597-66vd2mdu 2102 8 detected detect VBN cord-014597-66vd2mdu 2102 9 lipids lipid NNS cord-014597-66vd2mdu 2102 10 and and CC cord-014597-66vd2mdu 2102 11 to to TO cord-014597-66vd2mdu 2102 12 guarantee guarantee VB cord-014597-66vd2mdu 2102 13 comparable comparable JJ cord-014597-66vd2mdu 2102 14 results result NNS cord-014597-66vd2mdu 2102 15 between between IN cord-014597-66vd2mdu 2102 16 batches batch NNS cord-014597-66vd2mdu 2102 17 labeled label VBN cord-014597-66vd2mdu 2102 18 internal internal JJ cord-014597-66vd2mdu 2102 19 standard standard NN cord-014597-66vd2mdu 2102 20 were be VBD cord-014597-66vd2mdu 2102 21 added add VBN cord-014597-66vd2mdu 2102 22 prior prior RB cord-014597-66vd2mdu 2102 23 to to IN cord-014597-66vd2mdu 2102 24 extraction extraction NN cord-014597-66vd2mdu 2102 25 . . . cord-014597-66vd2mdu 2103 1 This this DT cord-014597-66vd2mdu 2103 2 method method NN cord-014597-66vd2mdu 2103 3 was be VBD cord-014597-66vd2mdu 2103 4 optimized optimize VBN cord-014597-66vd2mdu 2103 5 in in IN cord-014597-66vd2mdu 2103 6 a a DT cord-014597-66vd2mdu 2103 7 stepwise stepwise JJ cord-014597-66vd2mdu 2103 8 process process NN cord-014597-66vd2mdu 2103 9 to to TO cord-014597-66vd2mdu 2103 10 ensure ensure VB cord-014597-66vd2mdu 2103 11 a a DT cord-014597-66vd2mdu 2103 12 sensitive sensitive JJ cord-014597-66vd2mdu 2103 13 and and CC cord-014597-66vd2mdu 2103 14 selective selective JJ cord-014597-66vd2mdu 2103 15 measurement measurement NN cord-014597-66vd2mdu 2103 16 of of IN cord-014597-66vd2mdu 2103 17 the the DT cord-014597-66vd2mdu 2103 18 lipids lipid NNS cord-014597-66vd2mdu 2103 19 . . . cord-014597-66vd2mdu 2104 1 Lipids lipid NNS cord-014597-66vd2mdu 2104 2 were be VBD cord-014597-66vd2mdu 2104 3 extracted extract VBN cord-014597-66vd2mdu 2104 4 by by IN cord-014597-66vd2mdu 2104 5 Matyash Matyash NNP cord-014597-66vd2mdu 2104 6 method method NN cord-014597-66vd2mdu 2104 7 , , , cord-014597-66vd2mdu 2104 8 separated separate VBN cord-014597-66vd2mdu 2104 9 by by IN cord-014597-66vd2mdu 2104 10 HILIC HILIC NNP cord-014597-66vd2mdu 2104 11 and and CC cord-014597-66vd2mdu 2104 12 detected detect VBN cord-014597-66vd2mdu 2104 13 by by IN cord-014597-66vd2mdu 2104 14 tandem tandem JJ cord-014597-66vd2mdu 2104 15 mass mass NN cord-014597-66vd2mdu 2104 16 spectrometry spectrometry NN cord-014597-66vd2mdu 2104 17 . . . cord-014597-66vd2mdu 2105 1 This this DT cord-014597-66vd2mdu 2105 2 method method NN cord-014597-66vd2mdu 2105 3 is be VBZ cord-014597-66vd2mdu 2105 4 suitable suitable JJ cord-014597-66vd2mdu 2105 5 for for IN cord-014597-66vd2mdu 2105 6 both both DT cord-014597-66vd2mdu 2105 7 in in IN cord-014597-66vd2mdu 2105 8 process process NN cord-014597-66vd2mdu 2105 9 sample sample NN cord-014597-66vd2mdu 2105 10 lipid lipid NN cord-014597-66vd2mdu 2105 11 analysis analysis NN cord-014597-66vd2mdu 2105 12 providing provide VBG cord-014597-66vd2mdu 2105 13 information information NN cord-014597-66vd2mdu 2105 14 on on IN cord-014597-66vd2mdu 2105 15 the the DT cord-014597-66vd2mdu 2105 16 cell cell NN cord-014597-66vd2mdu 2105 17 lipid lipid NN cord-014597-66vd2mdu 2105 18 content content NN cord-014597-66vd2mdu 2105 19 , , , cord-014597-66vd2mdu 2105 20 and and CC cord-014597-66vd2mdu 2105 21 for for IN cord-014597-66vd2mdu 2105 22 harvest harvest NN cord-014597-66vd2mdu 2105 23 samples sample NNS cord-014597-66vd2mdu 2105 24 , , , cord-014597-66vd2mdu 2105 25 enabling enable VBG cord-014597-66vd2mdu 2105 26 to to TO cord-014597-66vd2mdu 2105 27 follow follow VB cord-014597-66vd2mdu 2105 28 the the DT cord-014597-66vd2mdu 2105 29 lipid lipid NN cord-014597-66vd2mdu 2105 30 release release NN cord-014597-66vd2mdu 2105 31 during during IN cord-014597-66vd2mdu 2105 32 the the DT cord-014597-66vd2mdu 2105 33 different different JJ cord-014597-66vd2mdu 2105 34 harvest harvest NN cord-014597-66vd2mdu 2105 35 steps step NNS cord-014597-66vd2mdu 2105 36 . . . cord-014597-66vd2mdu 2106 1 This this DT cord-014597-66vd2mdu 2106 2 non non JJ cord-014597-66vd2mdu 2106 3 - - JJ cord-014597-66vd2mdu 2106 4 targeted targeted JJ cord-014597-66vd2mdu 2106 5 lipidomic lipidomic JJ cord-014597-66vd2mdu 2106 6 quantitation quantitation NN cord-014597-66vd2mdu 2106 7 method method NN cord-014597-66vd2mdu 2106 8 will will MD cord-014597-66vd2mdu 2106 9 enable enable VB cord-014597-66vd2mdu 2106 10 us -PRON- PRP cord-014597-66vd2mdu 2106 11 to to TO cord-014597-66vd2mdu 2106 12 better well RBR cord-014597-66vd2mdu 2106 13 control control VB cord-014597-66vd2mdu 2106 14 lipid lipid NN cord-014597-66vd2mdu 2106 15 synthesis synthesis NN cord-014597-66vd2mdu 2106 16 during during IN cord-014597-66vd2mdu 2106 17 biopharmaceutical biopharmaceutical JJ cord-014597-66vd2mdu 2106 18 fed fed NNP cord-014597-66vd2mdu 2106 19 batch batch NN cord-014597-66vd2mdu 2106 20 production production NN cord-014597-66vd2mdu 2106 21 through through IN cord-014597-66vd2mdu 2106 22 clone clone NN cord-014597-66vd2mdu 2106 23 selection selection NN cord-014597-66vd2mdu 2106 24 , , , cord-014597-66vd2mdu 2106 25 metabolomics metabolomic NNS cord-014597-66vd2mdu 2106 26 studies study NNS cord-014597-66vd2mdu 2106 27 and and CC cord-014597-66vd2mdu 2106 28 harvest harvest VB cord-014597-66vd2mdu 2106 29 development development NN cord-014597-66vd2mdu 2106 30 . . . cord-014597-66vd2mdu 2107 1 Background Background NNP cord-014597-66vd2mdu 2107 2 Human human JJ cord-014597-66vd2mdu 2107 3 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2107 4 stem stem NN cord-014597-66vd2mdu 2107 5 / / SYM cord-014597-66vd2mdu 2107 6 stromal stromal NN cord-014597-66vd2mdu 2107 7 cells cell NNS cord-014597-66vd2mdu 2107 8 ( ( -LRB- cord-014597-66vd2mdu 2107 9 hMSC hmsc NN cord-014597-66vd2mdu 2107 10 ) ) -RRB- cord-014597-66vd2mdu 2107 11 can can MD cord-014597-66vd2mdu 2107 12 easily easily RB cord-014597-66vd2mdu 2107 13 be be VB cord-014597-66vd2mdu 2107 14 isolated isolate VBN cord-014597-66vd2mdu 2107 15 from from IN cord-014597-66vd2mdu 2107 16 e.g. e.g. JJ cord-014597-66vd2mdu 2107 17 bone bone NN cord-014597-66vd2mdu 2107 18 marrow marrow NN cord-014597-66vd2mdu 2107 19 , , , cord-014597-66vd2mdu 2107 20 fat fat JJ cord-014597-66vd2mdu 2107 21 tissue tissue NN cord-014597-66vd2mdu 2107 22 or or CC cord-014597-66vd2mdu 2107 23 umbilical umbilical JJ cord-014597-66vd2mdu 2107 24 cord cord NN cord-014597-66vd2mdu 2107 25 blood blood NN cord-014597-66vd2mdu 2107 26 and and CC cord-014597-66vd2mdu 2107 27 are be VBP cord-014597-66vd2mdu 2107 28 therefore therefore RB cord-014597-66vd2mdu 2107 29 a a DT cord-014597-66vd2mdu 2107 30 central central JJ cord-014597-66vd2mdu 2107 31 player player NN cord-014597-66vd2mdu 2107 32 in in IN cord-014597-66vd2mdu 2107 33 regenerative regenerative JJ cord-014597-66vd2mdu 2107 34 medicine medicine NN cord-014597-66vd2mdu 2107 35 , , , cord-014597-66vd2mdu 2107 36 gene gene NN cord-014597-66vd2mdu 2107 37 therapy therapy NN cord-014597-66vd2mdu 2107 38 and and CC cord-014597-66vd2mdu 2107 39 cell cell NN cord-014597-66vd2mdu 2107 40 therapy therapy NN cord-014597-66vd2mdu 2107 41 [ [ -LRB- cord-014597-66vd2mdu 2107 42 1 1 CD cord-014597-66vd2mdu 2107 43 ] ] -RRB- cord-014597-66vd2mdu 2107 44 [ [ -LRB- cord-014597-66vd2mdu 2107 45 2 2 CD cord-014597-66vd2mdu 2107 46 ] ] -RRB- cord-014597-66vd2mdu 2107 47 [ [ -LRB- cord-014597-66vd2mdu 2107 48 3 3 CD cord-014597-66vd2mdu 2107 49 ] ] -RRB- cord-014597-66vd2mdu 2107 50 . . . cord-014597-66vd2mdu 2108 1 The the DT cord-014597-66vd2mdu 2108 2 necessary necessary JJ cord-014597-66vd2mdu 2108 3 gene gene NN cord-014597-66vd2mdu 2108 4 shuttle shuttle NN cord-014597-66vd2mdu 2108 5 is be VBZ cord-014597-66vd2mdu 2108 6 mainly mainly RB cord-014597-66vd2mdu 2108 7 provided provide VBN cord-014597-66vd2mdu 2108 8 by by IN cord-014597-66vd2mdu 2108 9 viruses virus NNS cord-014597-66vd2mdu 2108 10 associated associate VBN cord-014597-66vd2mdu 2108 11 with with IN cord-014597-66vd2mdu 2108 12 diseases disease NNS cord-014597-66vd2mdu 2108 13 , , , cord-014597-66vd2mdu 2108 14 like like IN cord-014597-66vd2mdu 2108 15 retrovirus retrovirus NN cord-014597-66vd2mdu 2108 16 or or CC cord-014597-66vd2mdu 2108 17 adenovirus adenovirus NN cord-014597-66vd2mdu 2108 18 [ [ -LRB- cord-014597-66vd2mdu 2108 19 4 4 CD cord-014597-66vd2mdu 2108 20 ] ] -RRB- cord-014597-66vd2mdu 2108 21 [ [ -LRB- cord-014597-66vd2mdu 2108 22 5 5 CD cord-014597-66vd2mdu 2108 23 ] ] -RRB- cord-014597-66vd2mdu 2108 24 [ [ -LRB- cord-014597-66vd2mdu 2108 25 6 6 CD cord-014597-66vd2mdu 2108 26 ] ] -RRB- cord-014597-66vd2mdu 2108 27 [ [ -LRB- cord-014597-66vd2mdu 2108 28 7 7 CD cord-014597-66vd2mdu 2108 29 ] ] -RRB- cord-014597-66vd2mdu 2108 30 . . . cord-014597-66vd2mdu 2109 1 These these DT cord-014597-66vd2mdu 2109 2 possible possible JJ cord-014597-66vd2mdu 2109 3 pathogen pathogen NN cord-014597-66vd2mdu 2109 4 viruses virus NNS cord-014597-66vd2mdu 2109 5 demand demand VBP cord-014597-66vd2mdu 2109 6 for for IN cord-014597-66vd2mdu 2109 7 high high JJ cord-014597-66vd2mdu 2109 8 safety safety NN cord-014597-66vd2mdu 2109 9 standards standard NNS cord-014597-66vd2mdu 2109 10 . . . cord-014597-66vd2mdu 2110 1 Also also RB cord-014597-66vd2mdu 2110 2 , , , cord-014597-66vd2mdu 2110 3 they -PRON- PRP cord-014597-66vd2mdu 2110 4 are be VBP cord-014597-66vd2mdu 2110 5 prone prone JJ cord-014597-66vd2mdu 2110 6 to to IN cord-014597-66vd2mdu 2110 7 genomic genomic JJ cord-014597-66vd2mdu 2110 8 alterations alteration NNS cord-014597-66vd2mdu 2110 9 and and CC cord-014597-66vd2mdu 2110 10 there there EX cord-014597-66vd2mdu 2110 11 is be VBZ cord-014597-66vd2mdu 2110 12 the the DT cord-014597-66vd2mdu 2110 13 possibility possibility NN cord-014597-66vd2mdu 2110 14 of of IN cord-014597-66vd2mdu 2110 15 virus virus NN cord-014597-66vd2mdu 2110 16 inactivation inactivation NN cord-014597-66vd2mdu 2110 17 , , , cord-014597-66vd2mdu 2110 18 triggered trigger VBD cord-014597-66vd2mdu 2110 19 due due IN cord-014597-66vd2mdu 2110 20 to to IN cord-014597-66vd2mdu 2110 21 pre pre VB cord-014597-66vd2mdu 2110 22 - - JJ cord-014597-66vd2mdu 2110 23 existing existing JJ cord-014597-66vd2mdu 2110 24 immunity immunity NN cord-014597-66vd2mdu 2110 25 in in IN cord-014597-66vd2mdu 2110 26 the the DT cord-014597-66vd2mdu 2110 27 patient patient NN cord-014597-66vd2mdu 2110 28 [ [ -LRB- cord-014597-66vd2mdu 2110 29 8 8 CD cord-014597-66vd2mdu 2110 30 ] ] -RRB- cord-014597-66vd2mdu 2110 31 [ [ -LRB- cord-014597-66vd2mdu 2110 32 9 9 CD cord-014597-66vd2mdu 2110 33 ] ] -RRB- cord-014597-66vd2mdu 2110 34 [ [ -LRB- cord-014597-66vd2mdu 2110 35 10 10 CD cord-014597-66vd2mdu 2110 36 ] ] -RRB- cord-014597-66vd2mdu 2110 37 . . . cord-014597-66vd2mdu 2111 1 In in IN cord-014597-66vd2mdu 2111 2 this this DT cord-014597-66vd2mdu 2111 3 context context NN cord-014597-66vd2mdu 2111 4 , , , cord-014597-66vd2mdu 2111 5 the the DT cord-014597-66vd2mdu 2111 6 Autographa Autographa NNP cord-014597-66vd2mdu 2111 7 californica californica NN cord-014597-66vd2mdu 2111 8 multicapsid multicapsid NNP cord-014597-66vd2mdu 2111 9 nucleopolyhedrovirus nucleopolyhedrovirus NNP cord-014597-66vd2mdu 2111 10 ( ( -LRB- cord-014597-66vd2mdu 2111 11 AcMNPV AcMNPV NNP cord-014597-66vd2mdu 2111 12 ) ) -RRB- cord-014597-66vd2mdu 2111 13 is be VBZ cord-014597-66vd2mdu 2111 14 a a DT cord-014597-66vd2mdu 2111 15 safe safe JJ cord-014597-66vd2mdu 2111 16 alternative alternative NN cord-014597-66vd2mdu 2111 17 . . . cord-014597-66vd2mdu 2112 1 The the DT cord-014597-66vd2mdu 2112 2 virus virus NN cord-014597-66vd2mdu 2112 3 replication replication NN cord-014597-66vd2mdu 2112 4 is be VBZ cord-014597-66vd2mdu 2112 5 hostspecific hostspecific JJ cord-014597-66vd2mdu 2112 6 for for IN cord-014597-66vd2mdu 2112 7 insects insect NNS cord-014597-66vd2mdu 2112 8 [ [ -LRB- cord-014597-66vd2mdu 2112 9 11 11 CD cord-014597-66vd2mdu 2112 10 ] ] -RRB- cord-014597-66vd2mdu 2112 11 , , , cord-014597-66vd2mdu 2112 12 but but CC cord-014597-66vd2mdu 2112 13 it -PRON- PRP cord-014597-66vd2mdu 2112 14 is be VBZ cord-014597-66vd2mdu 2112 15 known know VBN cord-014597-66vd2mdu 2112 16 since since IN cord-014597-66vd2mdu 2112 17 the the DT cord-014597-66vd2mdu 2112 18 mid-90s mid-90 NNS cord-014597-66vd2mdu 2112 19 , , , cord-014597-66vd2mdu 2112 20 that that IN cord-014597-66vd2mdu 2112 21 a a DT cord-014597-66vd2mdu 2112 22 temporary temporary JJ cord-014597-66vd2mdu 2112 23 transduction transduction NN cord-014597-66vd2mdu 2112 24 of of IN cord-014597-66vd2mdu 2112 25 mammalian mammalian JJ cord-014597-66vd2mdu 2112 26 cells cell NNS cord-014597-66vd2mdu 2112 27 is be VBZ cord-014597-66vd2mdu 2112 28 possible possible JJ cord-014597-66vd2mdu 2112 29 [ [ -LRB- cord-014597-66vd2mdu 2112 30 12 12 CD cord-014597-66vd2mdu 2112 31 ] ] -RRB- cord-014597-66vd2mdu 2112 32 . . . cord-014597-66vd2mdu 2113 1 Some some DT cord-014597-66vd2mdu 2113 2 modifications modification NNS cord-014597-66vd2mdu 2113 3 of of IN cord-014597-66vd2mdu 2113 4 the the DT cord-014597-66vd2mdu 2113 5 virus virus NN cord-014597-66vd2mdu 2113 6 increased increase VBD cord-014597-66vd2mdu 2113 7 the the DT cord-014597-66vd2mdu 2113 8 applicability applicability NN cord-014597-66vd2mdu 2113 9 in in IN cord-014597-66vd2mdu 2113 10 stem stem NN cord-014597-66vd2mdu 2113 11 cells cell NNS cord-014597-66vd2mdu 2113 12 . . . cord-014597-66vd2mdu 2114 1 Pseudotyping pseudotype VBG cord-014597-66vd2mdu 2114 2 the the DT cord-014597-66vd2mdu 2114 3 virus virus NN cord-014597-66vd2mdu 2114 4 with with IN cord-014597-66vd2mdu 2114 5 the the DT cord-014597-66vd2mdu 2114 6 vesicular vesicular JJ cord-014597-66vd2mdu 2114 7 stomatitis stomatitis NN cord-014597-66vd2mdu 2114 8 glycoprotein glycoprotein NN cord-014597-66vd2mdu 2114 9 ( ( -LRB- cord-014597-66vd2mdu 2114 10 VSV VSV NNP cord-014597-66vd2mdu 2114 11 - - HYPH cord-014597-66vd2mdu 2114 12 G G NNP cord-014597-66vd2mdu 2114 13 ) ) -RRB- cord-014597-66vd2mdu 2114 14 led lead VBD cord-014597-66vd2mdu 2114 15 to to IN cord-014597-66vd2mdu 2114 16 an an DT cord-014597-66vd2mdu 2114 17 expansion expansion NN cord-014597-66vd2mdu 2114 18 of of IN cord-014597-66vd2mdu 2114 19 the the DT cord-014597-66vd2mdu 2114 20 transducable transducable JJ cord-014597-66vd2mdu 2114 21 cell cell NN cord-014597-66vd2mdu 2114 22 [ [ -LRB- cord-014597-66vd2mdu 2114 23 13 13 CD cord-014597-66vd2mdu 2114 24 , , , cord-014597-66vd2mdu 2114 25 14 14 CD cord-014597-66vd2mdu 2114 26 ] ] -RRB- cord-014597-66vd2mdu 2114 27 and and CC cord-014597-66vd2mdu 2114 28 the the DT cord-014597-66vd2mdu 2114 29 integration integration NN cord-014597-66vd2mdu 2114 30 of of IN cord-014597-66vd2mdu 2114 31 the the DT cord-014597-66vd2mdu 2114 32 woodchuck woodchuck NNP cord-014597-66vd2mdu 2114 33 hepatitis hepatitis NNP cord-014597-66vd2mdu 2114 34 virus virus NN cord-014597-66vd2mdu 2114 35 post post JJ cord-014597-66vd2mdu 2114 36 - - JJ cord-014597-66vd2mdu 2114 37 transcriptional transcriptional JJ cord-014597-66vd2mdu 2114 38 regulatory regulatory JJ cord-014597-66vd2mdu 2114 39 element element NN cord-014597-66vd2mdu 2114 40 ( ( -LRB- cord-014597-66vd2mdu 2114 41 WPRE WPRE NNP cord-014597-66vd2mdu 2114 42 ) ) -RRB- cord-014597-66vd2mdu 2114 43 prolonged prolong VBD cord-014597-66vd2mdu 2114 44 the the DT cord-014597-66vd2mdu 2114 45 recombinant recombinant JJ cord-014597-66vd2mdu 2114 46 protein protein NN cord-014597-66vd2mdu 2114 47 expression expression NN cord-014597-66vd2mdu 2114 48 [ [ -LRB- cord-014597-66vd2mdu 2114 49 15 15 CD cord-014597-66vd2mdu 2114 50 , , , cord-014597-66vd2mdu 2114 51 16 16 CD cord-014597-66vd2mdu 2114 52 ] ] -RRB- cord-014597-66vd2mdu 2114 53 . . . cord-014597-66vd2mdu 2115 1 For for IN cord-014597-66vd2mdu 2115 2 achieving achieve VBG cord-014597-66vd2mdu 2115 3 a a DT cord-014597-66vd2mdu 2115 4 baculovirus baculovirus NN cord-014597-66vd2mdu 2115 5 - - HYPH cord-014597-66vd2mdu 2115 6 induced induce VBN cord-014597-66vd2mdu 2115 7 differentiation differentiation NN cord-014597-66vd2mdu 2115 8 of of IN cord-014597-66vd2mdu 2115 9 hMSCs hMSCs NNP cord-014597-66vd2mdu 2115 10 , , , cord-014597-66vd2mdu 2115 11 the the DT cord-014597-66vd2mdu 2115 12 promotor promotor NN cord-014597-66vd2mdu 2115 13 and and CC cord-014597-66vd2mdu 2115 14 the the DT cord-014597-66vd2mdu 2115 15 expression expression NN cord-014597-66vd2mdu 2115 16 strength strength NN cord-014597-66vd2mdu 2115 17 of of IN cord-014597-66vd2mdu 2115 18 the the DT cord-014597-66vd2mdu 2115 19 recombinant recombinant JJ cord-014597-66vd2mdu 2115 20 protein protein NN cord-014597-66vd2mdu 2115 21 are be VBP cord-014597-66vd2mdu 2115 22 crucial crucial JJ cord-014597-66vd2mdu 2115 23 factors factor NNS cord-014597-66vd2mdu 2115 24 . . . cord-014597-66vd2mdu 2116 1 Still still RB cord-014597-66vd2mdu 2116 2 , , , cord-014597-66vd2mdu 2116 3 there there EX cord-014597-66vd2mdu 2116 4 are be VBP cord-014597-66vd2mdu 2116 5 still still RB cord-014597-66vd2mdu 2116 6 few few JJ cord-014597-66vd2mdu 2116 7 comparative comparative JJ cord-014597-66vd2mdu 2116 8 promotor promotor NN cord-014597-66vd2mdu 2116 9 studies study NNS cord-014597-66vd2mdu 2116 10 [ [ -LRB- cord-014597-66vd2mdu 2116 11 17 17 CD cord-014597-66vd2mdu 2116 12 , , , cord-014597-66vd2mdu 2116 13 18 18 CD cord-014597-66vd2mdu 2116 14 ] ] -RRB- cord-014597-66vd2mdu 2116 15 . . . cord-014597-66vd2mdu 2117 1 However however RB cord-014597-66vd2mdu 2117 2 , , , cord-014597-66vd2mdu 2117 3 a a DT cord-014597-66vd2mdu 2117 4 successful successful JJ cord-014597-66vd2mdu 2117 5 virus virus NN cord-014597-66vd2mdu 2117 6 uptake uptake NN cord-014597-66vd2mdu 2117 7 is be VBZ cord-014597-66vd2mdu 2117 8 the the DT cord-014597-66vd2mdu 2117 9 prerequisite prerequisite NN cord-014597-66vd2mdu 2117 10 for for IN cord-014597-66vd2mdu 2117 11 a a DT cord-014597-66vd2mdu 2117 12 successful successful JJ cord-014597-66vd2mdu 2117 13 protein protein NN cord-014597-66vd2mdu 2117 14 expression expression NN cord-014597-66vd2mdu 2117 15 . . . cord-014597-66vd2mdu 2118 1 We -PRON- PRP cord-014597-66vd2mdu 2118 2 therefore therefore RB cord-014597-66vd2mdu 2118 3 investigated investigate VBD cord-014597-66vd2mdu 2118 4 factors factor NNS cord-014597-66vd2mdu 2118 5 significantly significantly RB cord-014597-66vd2mdu 2118 6 influencing influence VBG cord-014597-66vd2mdu 2118 7 the the DT cord-014597-66vd2mdu 2118 8 transduction transduction NN cord-014597-66vd2mdu 2118 9 process process NN cord-014597-66vd2mdu 2118 10 by by IN cord-014597-66vd2mdu 2118 11 applying apply VBG cord-014597-66vd2mdu 2118 12 design design NN cord-014597-66vd2mdu 2118 13 of of IN cord-014597-66vd2mdu 2118 14 experiments experiment NNS cord-014597-66vd2mdu 2118 15 ( ( -LRB- cord-014597-66vd2mdu 2118 16 s. s. NNP cord-014597-66vd2mdu 2118 17 Fig Fig NNP cord-014597-66vd2mdu 2118 18 . . . cord-014597-66vd2mdu 2118 19 1a 1a CD cord-014597-66vd2mdu 2118 20 ) ) -RRB- cord-014597-66vd2mdu 2118 21 . . . cord-014597-66vd2mdu 2119 1 The the DT cord-014597-66vd2mdu 2119 2 experimental experimental JJ cord-014597-66vd2mdu 2119 3 design design NN cord-014597-66vd2mdu 2119 4 comprises comprise VBZ cord-014597-66vd2mdu 2119 5 a a DT cord-014597-66vd2mdu 2119 6 two two CD cord-014597-66vd2mdu 2119 7 level level NN cord-014597-66vd2mdu 2119 8 factorial factorial NN cord-014597-66vd2mdu 2119 9 screening screening NN cord-014597-66vd2mdu 2119 10 , , , cord-014597-66vd2mdu 2119 11 set set NN cord-014597-66vd2mdu 2119 12 - - HYPH cord-014597-66vd2mdu 2119 13 up up NN cord-014597-66vd2mdu 2119 14 using use VBG cord-014597-66vd2mdu 2119 15 Design Design NNP cord-014597-66vd2mdu 2119 16 Expert expert NN cord-014597-66vd2mdu 2119 17 V9.For V9.For NNP cord-014597-66vd2mdu 2120 1 the the DT cord-014597-66vd2mdu 2120 2 transduction transduction NN cord-014597-66vd2mdu 2120 3 60,000 60,000 CD cord-014597-66vd2mdu 2120 4 c c NN cord-014597-66vd2mdu 2120 5 / / SYM cord-014597-66vd2mdu 2120 6 cm cm NNP cord-014597-66vd2mdu 2120 7 2 2 CD cord-014597-66vd2mdu 2120 8 were be VBD cord-014597-66vd2mdu 2120 9 seeded seed VBN cord-014597-66vd2mdu 2120 10 in in IN cord-014597-66vd2mdu 2120 11 24-well 24-well CD cord-014597-66vd2mdu 2120 12 plates plate NNS cord-014597-66vd2mdu 2120 13 with with IN cord-014597-66vd2mdu 2120 14 DMEM DMEM NNP cord-014597-66vd2mdu 2120 15 + + CC cord-014597-66vd2mdu 2120 16 10 10 CD cord-014597-66vd2mdu 2120 17 % % NN cord-014597-66vd2mdu 2120 18 FCS FCS NNP cord-014597-66vd2mdu 2120 19 and and CC cord-014597-66vd2mdu 2120 20 incubated incubate VBN cord-014597-66vd2mdu 2120 21 overnight overnight RB cord-014597-66vd2mdu 2120 22 at at IN cord-014597-66vd2mdu 2120 23 37 37 CD cord-014597-66vd2mdu 2120 24 ° ° NN cord-014597-66vd2mdu 2120 25 C c NN cord-014597-66vd2mdu 2120 26 , , , cord-014597-66vd2mdu 2120 27 8 8 CD cord-014597-66vd2mdu 2120 28 % % NN cord-014597-66vd2mdu 2120 29 CO co NN cord-014597-66vd2mdu 2120 30 2 2 CD cord-014597-66vd2mdu 2120 31 and and CC cord-014597-66vd2mdu 2120 32 humidified humidified JJ cord-014597-66vd2mdu 2120 33 atmosphere atmosphere NN cord-014597-66vd2mdu 2120 34 . . . cord-014597-66vd2mdu 2121 1 The the DT cord-014597-66vd2mdu 2121 2 recombinant recombinant JJ cord-014597-66vd2mdu 2121 3 baculovirus baculovirus NN cord-014597-66vd2mdu 2121 4 using use VBG cord-014597-66vd2mdu 2121 5 an an DT cord-014597-66vd2mdu 2121 6 integrated integrate VBN cord-014597-66vd2mdu 2121 7 EF1α EF1α NNP cord-014597-66vd2mdu 2121 8 promoter promoter NN cord-014597-66vd2mdu 2121 9 to to TO cord-014597-66vd2mdu 2121 10 control control VB cord-014597-66vd2mdu 2121 11 GFP GFP NNP cord-014597-66vd2mdu 2121 12 expression expression NN cord-014597-66vd2mdu 2121 13 , , , cord-014597-66vd2mdu 2121 14 described describe VBN cord-014597-66vd2mdu 2121 15 elsewhere elsewhere RB cord-014597-66vd2mdu 2121 16 [ [ -LRB- cord-014597-66vd2mdu 2121 17 18 18 CD cord-014597-66vd2mdu 2121 18 ] ] -RRB- cord-014597-66vd2mdu 2121 19 , , , cord-014597-66vd2mdu 2121 20 was be VBD cord-014597-66vd2mdu 2121 21 diluted dilute VBN cord-014597-66vd2mdu 2121 22 to to IN cord-014597-66vd2mdu 2121 23 the the DT cord-014597-66vd2mdu 2121 24 respective respective JJ cord-014597-66vd2mdu 2121 25 concentrations concentration NNS cord-014597-66vd2mdu 2121 26 in in IN cord-014597-66vd2mdu 2121 27 the the DT cord-014597-66vd2mdu 2121 28 different different JJ cord-014597-66vd2mdu 2121 29 surrounding surround VBG cord-014597-66vd2mdu 2121 30 fluids fluid NNS cord-014597-66vd2mdu 2121 31 . . . cord-014597-66vd2mdu 2122 1 After after IN cord-014597-66vd2mdu 2122 2 discarding discard VBG cord-014597-66vd2mdu 2122 3 the the DT cord-014597-66vd2mdu 2122 4 cultivation cultivation NN cord-014597-66vd2mdu 2122 5 medium medium NN cord-014597-66vd2mdu 2122 6 of of IN cord-014597-66vd2mdu 2122 7 the the DT cord-014597-66vd2mdu 2122 8 hMSC hmsc NN cord-014597-66vd2mdu 2122 9 - - HYPH cord-014597-66vd2mdu 2122 10 TERT TERT NNP cord-014597-66vd2mdu 2122 11 , , , cord-014597-66vd2mdu 2122 12 1 1 CD cord-014597-66vd2mdu 2122 13 mL ml NN cord-014597-66vd2mdu 2122 14 of of IN cord-014597-66vd2mdu 2122 15 virus virus NN cord-014597-66vd2mdu 2122 16 containing contain VBG cord-014597-66vd2mdu 2122 17 solution solution NN cord-014597-66vd2mdu 2122 18 was be VBD cord-014597-66vd2mdu 2122 19 added add VBN cord-014597-66vd2mdu 2122 20 to to IN cord-014597-66vd2mdu 2122 21 the the DT cord-014597-66vd2mdu 2122 22 cells cell NNS cord-014597-66vd2mdu 2122 23 . . . cord-014597-66vd2mdu 2123 1 The the DT cord-014597-66vd2mdu 2123 2 following follow VBG cord-014597-66vd2mdu 2123 3 incubation incubation NN cord-014597-66vd2mdu 2123 4 was be VBD cord-014597-66vd2mdu 2123 5 varied varied JJ cord-014597-66vd2mdu 2123 6 in in IN cord-014597-66vd2mdu 2123 7 duration duration NN cord-014597-66vd2mdu 2123 8 before before IN cord-014597-66vd2mdu 2123 9 replacing replace VBG cord-014597-66vd2mdu 2123 10 the the DT cord-014597-66vd2mdu 2123 11 virus virus NN cord-014597-66vd2mdu 2123 12 solution solution NN cord-014597-66vd2mdu 2123 13 with with IN cord-014597-66vd2mdu 2123 14 growth growth NN cord-014597-66vd2mdu 2123 15 medium medium NN cord-014597-66vd2mdu 2123 16 and and CC cord-014597-66vd2mdu 2123 17 an an DT cord-014597-66vd2mdu 2123 18 incubation incubation NN cord-014597-66vd2mdu 2123 19 overnight overnight RB cord-014597-66vd2mdu 2123 20 . . . cord-014597-66vd2mdu 2124 1 24 24 CD cord-014597-66vd2mdu 2124 2 h h NN cord-014597-66vd2mdu 2124 3 post post NN cord-014597-66vd2mdu 2124 4 transduction transduction NN cord-014597-66vd2mdu 2124 5 ( ( -LRB- cord-014597-66vd2mdu 2124 6 hpt hpt NNP cord-014597-66vd2mdu 2124 7 ) ) -RRB- cord-014597-66vd2mdu 2124 8 the the DT cord-014597-66vd2mdu 2124 9 cells cell NNS cord-014597-66vd2mdu 2124 10 were be VBD cord-014597-66vd2mdu 2124 11 washed wash VBN cord-014597-66vd2mdu 2124 12 with with IN cord-014597-66vd2mdu 2124 13 PBS PBS NNP cord-014597-66vd2mdu 2124 14 , , , cord-014597-66vd2mdu 2124 15 trypsinized trypsinize VBN cord-014597-66vd2mdu 2124 16 with with IN cord-014597-66vd2mdu 2124 17 100 100 CD cord-014597-66vd2mdu 2124 18 μL μL NNP cord-014597-66vd2mdu 2124 19 Trypsin Trypsin NNP cord-014597-66vd2mdu 2124 20 / / SYM cord-014597-66vd2mdu 2124 21 EDTA EDTA NNP cord-014597-66vd2mdu 2124 22 and and CC cord-014597-66vd2mdu 2124 23 incubated incubate VBN cord-014597-66vd2mdu 2124 24 for for IN cord-014597-66vd2mdu 2124 25 5 5 CD cord-014597-66vd2mdu 2124 26 min min NN cord-014597-66vd2mdu 2124 27 at at IN cord-014597-66vd2mdu 2124 28 37 37 CD cord-014597-66vd2mdu 2124 29 ° ° NN cord-014597-66vd2mdu 2124 30 C c NN cord-014597-66vd2mdu 2124 31 . . . cord-014597-66vd2mdu 2125 1 Trypsination trypsination NN cord-014597-66vd2mdu 2125 2 was be VBD cord-014597-66vd2mdu 2125 3 then then RB cord-014597-66vd2mdu 2125 4 stopped stop VBN cord-014597-66vd2mdu 2125 5 applying apply VBG cord-014597-66vd2mdu 2125 6 100 100 CD cord-014597-66vd2mdu 2125 7 μL μl CD cord-014597-66vd2mdu 2125 8 soybean soybean NN cord-014597-66vd2mdu 2125 9 trypsin trypsin NN cord-014597-66vd2mdu 2125 10 inhibitor inhibitor NN cord-014597-66vd2mdu 2125 11 and and CC cord-014597-66vd2mdu 2125 12 the the DT cord-014597-66vd2mdu 2125 13 cells cell NNS cord-014597-66vd2mdu 2125 14 were be VBD cord-014597-66vd2mdu 2125 15 analyzed analyze VBN cord-014597-66vd2mdu 2125 16 using use VBG cord-014597-66vd2mdu 2125 17 flow flow NN cord-014597-66vd2mdu 2125 18 cytometry cytometry NN cord-014597-66vd2mdu 2125 19 . . . cord-014597-66vd2mdu 2126 1 As as IN cord-014597-66vd2mdu 2126 2 shown show VBN cord-014597-66vd2mdu 2126 3 in in IN cord-014597-66vd2mdu 2126 4 Fig Fig NNP cord-014597-66vd2mdu 2126 5 . . . cord-014597-66vd2mdu 2127 1 1a 1a LS cord-014597-66vd2mdu 2127 2 , , , cord-014597-66vd2mdu 2127 3 the the DT cord-014597-66vd2mdu 2127 4 virus virus NN cord-014597-66vd2mdu 2127 5 concentration concentration NN cord-014597-66vd2mdu 2127 6 and and CC cord-014597-66vd2mdu 2127 7 incubation incubation NN cord-014597-66vd2mdu 2127 8 time time NN cord-014597-66vd2mdu 2127 9 exert exert VB cord-014597-66vd2mdu 2127 10 the the DT cord-014597-66vd2mdu 2127 11 highest high JJS cord-014597-66vd2mdu 2127 12 influence influence NN cord-014597-66vd2mdu 2127 13 on on IN cord-014597-66vd2mdu 2127 14 the the DT cord-014597-66vd2mdu 2127 15 transduction transduction NN cord-014597-66vd2mdu 2127 16 efficiency efficiency NN cord-014597-66vd2mdu 2127 17 . . . cord-014597-66vd2mdu 2128 1 Obviously obviously RB cord-014597-66vd2mdu 2128 2 , , , cord-014597-66vd2mdu 2128 3 a a DT cord-014597-66vd2mdu 2128 4 higher high JJR cord-014597-66vd2mdu 2128 5 concentration concentration NN cord-014597-66vd2mdu 2128 6 of of IN cord-014597-66vd2mdu 2128 7 viral viral JJ cord-014597-66vd2mdu 2128 8 particles particle NNS cord-014597-66vd2mdu 2128 9 and and CC cord-014597-66vd2mdu 2128 10 longer long JJR cord-014597-66vd2mdu 2128 11 incubation incubation NN cord-014597-66vd2mdu 2128 12 of of IN cord-014597-66vd2mdu 2128 13 cells cell NNS cord-014597-66vd2mdu 2128 14 with with IN cord-014597-66vd2mdu 2128 15 virus virus NN cord-014597-66vd2mdu 2128 16 increases increase VBZ cord-014597-66vd2mdu 2128 17 the the DT cord-014597-66vd2mdu 2128 18 probability probability NN cord-014597-66vd2mdu 2128 19 for for IN cord-014597-66vd2mdu 2128 20 hits hit NNS cord-014597-66vd2mdu 2128 21 between between IN cord-014597-66vd2mdu 2128 22 cells cell NNS cord-014597-66vd2mdu 2128 23 and and CC cord-014597-66vd2mdu 2128 24 virus virus NN cord-014597-66vd2mdu 2128 25 particles particle NNS cord-014597-66vd2mdu 2128 26 . . . cord-014597-66vd2mdu 2129 1 Additionally additionally RB cord-014597-66vd2mdu 2129 2 , , , cord-014597-66vd2mdu 2129 3 the the DT cord-014597-66vd2mdu 2129 4 surrounding surround VBG cord-014597-66vd2mdu 2129 5 fluid fluid NN cord-014597-66vd2mdu 2129 6 can can MD cord-014597-66vd2mdu 2129 7 have have VB cord-014597-66vd2mdu 2129 8 a a DT cord-014597-66vd2mdu 2129 9 negative negative JJ cord-014597-66vd2mdu 2129 10 impact impact NN cord-014597-66vd2mdu 2129 11 on on IN cord-014597-66vd2mdu 2129 12 the the DT cord-014597-66vd2mdu 2129 13 transduction transduction NN cord-014597-66vd2mdu 2129 14 . . . cord-014597-66vd2mdu 2130 1 This this DT cord-014597-66vd2mdu 2130 2 is be VBZ cord-014597-66vd2mdu 2130 3 due due JJ cord-014597-66vd2mdu 2130 4 to to IN cord-014597-66vd2mdu 2130 5 the the DT cord-014597-66vd2mdu 2130 6 interaction interaction NN cord-014597-66vd2mdu 2130 7 of of IN cord-014597-66vd2mdu 2130 8 medium medium JJ cord-014597-66vd2mdu 2130 9 components component NNS cord-014597-66vd2mdu 2130 10 with with IN cord-014597-66vd2mdu 2130 11 the the DT cord-014597-66vd2mdu 2130 12 baculovirus baculovirus NN cord-014597-66vd2mdu 2130 13 . . . cord-014597-66vd2mdu 2131 1 Therefore therefore RB cord-014597-66vd2mdu 2131 2 , , , cord-014597-66vd2mdu 2131 3 PBS PBS NNP cord-014597-66vd2mdu 2131 4 containing contain VBG cord-014597-66vd2mdu 2131 5 Ca Ca NNP cord-014597-66vd2mdu 2131 6 2 2 CD cord-014597-66vd2mdu 2131 7 + + SYM cord-014597-66vd2mdu 2131 8 & & CC cord-014597-66vd2mdu 2131 9 Mg Mg NNP cord-014597-66vd2mdu 2131 10 2 2 CD cord-014597-66vd2mdu 2132 1 + + UH cord-014597-66vd2mdu 2132 2 is be VBZ cord-014597-66vd2mdu 2132 3 recommended recommend VBN cord-014597-66vd2mdu 2132 4 as as IN cord-014597-66vd2mdu 2132 5 surrounding surround VBG cord-014597-66vd2mdu 2132 6 fluid fluid NN cord-014597-66vd2mdu 2132 7 for for IN cord-014597-66vd2mdu 2132 8 transduction transduction NN cord-014597-66vd2mdu 2132 9 experiments experiment NNS cord-014597-66vd2mdu 2132 10 . . . cord-014597-66vd2mdu 2133 1 In in IN cord-014597-66vd2mdu 2133 2 Fig Fig NNP cord-014597-66vd2mdu 2133 3 . . . cord-014597-66vd2mdu 2134 1 1B 1B NNP cord-014597-66vd2mdu 2134 2 , , , cord-014597-66vd2mdu 2134 3 the the DT cord-014597-66vd2mdu 2134 4 transduction transduction NN cord-014597-66vd2mdu 2134 5 conditions condition NNS cord-014597-66vd2mdu 2134 6 resulting result VBG cord-014597-66vd2mdu 2134 7 in in IN cord-014597-66vd2mdu 2134 8 the the DT cord-014597-66vd2mdu 2134 9 highest high JJS cord-014597-66vd2mdu 2134 10 percentage percentage NN cord-014597-66vd2mdu 2134 11 of of IN cord-014597-66vd2mdu 2134 12 GFP+ GFP+ NNP cord-014597-66vd2mdu 2134 13 cells cell NNS cord-014597-66vd2mdu 2134 14 are be VBP cord-014597-66vd2mdu 2134 15 displayed display VBN cord-014597-66vd2mdu 2134 16 : : : cord-014597-66vd2mdu 2134 17 150 150 CD cord-014597-66vd2mdu 2134 18 virus virus NN cord-014597-66vd2mdu 2134 19 particles particle NNS cord-014597-66vd2mdu 2134 20 per per IN cord-014597-66vd2mdu 2134 21 cell cell NN cord-014597-66vd2mdu 2134 22 ( ( -LRB- cord-014597-66vd2mdu 2134 23 PPC PPC NNP cord-014597-66vd2mdu 2134 24 ) ) -RRB- cord-014597-66vd2mdu 2134 25 and and CC cord-014597-66vd2mdu 2134 26 an an DT cord-014597-66vd2mdu 2134 27 incubation incubation NN cord-014597-66vd2mdu 2134 28 time time NN cord-014597-66vd2mdu 2134 29 of of IN cord-014597-66vd2mdu 2134 30 5 5 CD cord-014597-66vd2mdu 2134 31 h h NN cord-014597-66vd2mdu 2134 32 with with IN cord-014597-66vd2mdu 2134 33 hMSC hmsc NN cord-014597-66vd2mdu 2134 34 - - HYPH cord-014597-66vd2mdu 2134 35 TERT tert NN cord-014597-66vd2mdu 2134 36 . . . cord-014597-66vd2mdu 2135 1 The the DT cord-014597-66vd2mdu 2135 2 experiments experiment NNS cord-014597-66vd2mdu 2135 3 show show VBP cord-014597-66vd2mdu 2135 4 , , , cord-014597-66vd2mdu 2135 5 that that IN cord-014597-66vd2mdu 2135 6 especially especially RB cord-014597-66vd2mdu 2135 7 the the DT cord-014597-66vd2mdu 2135 8 virus virus NN cord-014597-66vd2mdu 2135 9 concentration concentration NN cord-014597-66vd2mdu 2135 10 and and CC cord-014597-66vd2mdu 2135 11 the the DT cord-014597-66vd2mdu 2135 12 incubation incubation NN cord-014597-66vd2mdu 2135 13 time time NN cord-014597-66vd2mdu 2135 14 of of IN cord-014597-66vd2mdu 2135 15 cells cell NNS cord-014597-66vd2mdu 2135 16 with with IN cord-014597-66vd2mdu 2135 17 virus virus NN cord-014597-66vd2mdu 2135 18 influence influence NN cord-014597-66vd2mdu 2135 19 the the DT cord-014597-66vd2mdu 2135 20 transduction transduction NN cord-014597-66vd2mdu 2135 21 efficiency efficiency NN cord-014597-66vd2mdu 2135 22 . . . cord-014597-66vd2mdu 2136 1 Based base VBN cord-014597-66vd2mdu 2136 2 on on IN cord-014597-66vd2mdu 2136 3 the the DT cord-014597-66vd2mdu 2136 4 results result NNS cord-014597-66vd2mdu 2136 5 of of IN cord-014597-66vd2mdu 2136 6 the the DT cord-014597-66vd2mdu 2136 7 screening screening NN cord-014597-66vd2mdu 2136 8 , , , cord-014597-66vd2mdu 2136 9 further further JJ cord-014597-66vd2mdu 2136 10 optimization optimization NN cord-014597-66vd2mdu 2136 11 of of IN cord-014597-66vd2mdu 2136 12 the the DT cord-014597-66vd2mdu 2136 13 transduction transduction NN cord-014597-66vd2mdu 2136 14 conditions condition NNS cord-014597-66vd2mdu 2136 15 will will MD cord-014597-66vd2mdu 2136 16 be be VB cord-014597-66vd2mdu 2136 17 done do VBN cord-014597-66vd2mdu 2136 18 using use VBG cord-014597-66vd2mdu 2136 19 a a DT cord-014597-66vd2mdu 2136 20 face face NN cord-014597-66vd2mdu 2136 21 centered center VBN cord-014597-66vd2mdu 2136 22 central central JJ cord-014597-66vd2mdu 2136 23 composite composite JJ cord-014597-66vd2mdu 2136 24 design design NN cord-014597-66vd2mdu 2136 25 with with IN cord-014597-66vd2mdu 2136 26 PBS PBS NNP cord-014597-66vd2mdu 2136 27 containing contain VBG cord-014597-66vd2mdu 2136 28 Ca Ca NNP cord-014597-66vd2mdu 2136 29 2 2 CD cord-014597-66vd2mdu 2137 1 + + CC cord-014597-66vd2mdu 2138 1 & & CC cord-014597-66vd2mdu 2138 2 Mg Mg NNP cord-014597-66vd2mdu 2138 3 2 2 CD cord-014597-66vd2mdu 2138 4 + + SYM cord-014597-66vd2mdu 2138 5 as as IN cord-014597-66vd2mdu 2138 6 surrounding surround VBG cord-014597-66vd2mdu 2138 7 fluid fluid NN cord-014597-66vd2mdu 2138 8 and and CC cord-014597-66vd2mdu 2138 9 at at IN cord-014597-66vd2mdu 2138 10 an an DT cord-014597-66vd2mdu 2138 11 incubation incubation NN cord-014597-66vd2mdu 2138 12 temperature temperature NN cord-014597-66vd2mdu 2138 13 of of IN cord-014597-66vd2mdu 2138 14 37 37 CD cord-014597-66vd2mdu 2138 15 ° ° NN cord-014597-66vd2mdu 2138 16 C c NN cord-014597-66vd2mdu 2138 17 . . . cord-014597-66vd2mdu 2139 1 Background background NN cord-014597-66vd2mdu 2139 2 Breast breast NN cord-014597-66vd2mdu 2139 3 cancer cancer NN cord-014597-66vd2mdu 2139 4 is be VBZ cord-014597-66vd2mdu 2139 5 the the DT cord-014597-66vd2mdu 2139 6 second second JJ cord-014597-66vd2mdu 2139 7 main main JJ cord-014597-66vd2mdu 2139 8 cause cause NN cord-014597-66vd2mdu 2139 9 of of IN cord-014597-66vd2mdu 2139 10 cancer cancer NN cord-014597-66vd2mdu 2139 11 related relate VBN cord-014597-66vd2mdu 2139 12 deaths death NNS cord-014597-66vd2mdu 2139 13 for for IN cord-014597-66vd2mdu 2139 14 women woman NNS cord-014597-66vd2mdu 2139 15 worldwide worldwide RB cord-014597-66vd2mdu 2139 16 and and CC cord-014597-66vd2mdu 2139 17 among among IN cord-014597-66vd2mdu 2139 18 them -PRON- PRP cord-014597-66vd2mdu 2139 19 the the DT cord-014597-66vd2mdu 2139 20 triple triple JJ cord-014597-66vd2mdu 2139 21 negative negative JJ cord-014597-66vd2mdu 2139 22 subtype subtype NN cord-014597-66vd2mdu 2139 23 ( ( -LRB- cord-014597-66vd2mdu 2139 24 TNBC TNBC NNP cord-014597-66vd2mdu 2139 25 ) ) -RRB- cord-014597-66vd2mdu 2139 26 represents represent VBZ cord-014597-66vd2mdu 2139 27 a a DT cord-014597-66vd2mdu 2139 28 clinical clinical JJ cord-014597-66vd2mdu 2139 29 challenge challenge NN cord-014597-66vd2mdu 2139 30 by by IN cord-014597-66vd2mdu 2139 31 being be VBG cord-014597-66vd2mdu 2139 32 associated associate VBN cord-014597-66vd2mdu 2139 33 with with IN cord-014597-66vd2mdu 2139 34 high high JJ cord-014597-66vd2mdu 2139 35 mortality mortality NN cord-014597-66vd2mdu 2139 36 and and CC cord-014597-66vd2mdu 2139 37 having have VBG cord-014597-66vd2mdu 2139 38 no no DT cord-014597-66vd2mdu 2139 39 effective effective JJ cord-014597-66vd2mdu 2139 40 therapies therapy NNS cord-014597-66vd2mdu 2139 41 against against IN cord-014597-66vd2mdu 2139 42 it -PRON- PRP cord-014597-66vd2mdu 2139 43 [ [ -LRB- cord-014597-66vd2mdu 2139 44 1 1 CD cord-014597-66vd2mdu 2139 45 ] ] -RRB- cord-014597-66vd2mdu 2139 46 , , , cord-014597-66vd2mdu 2139 47 [ [ -LRB- cord-014597-66vd2mdu 2139 48 2 2 CD cord-014597-66vd2mdu 2139 49 ] ] -RRB- cord-014597-66vd2mdu 2139 50 . . . cord-014597-66vd2mdu 2140 1 Accordingly accordingly RB cord-014597-66vd2mdu 2140 2 , , , cord-014597-66vd2mdu 2140 3 there there EX cord-014597-66vd2mdu 2140 4 is be VBZ cord-014597-66vd2mdu 2140 5 an an DT cord-014597-66vd2mdu 2140 6 urgent urgent JJ cord-014597-66vd2mdu 2140 7 need need NN cord-014597-66vd2mdu 2140 8 to to TO cord-014597-66vd2mdu 2140 9 design design VB cord-014597-66vd2mdu 2140 10 new new JJ cord-014597-66vd2mdu 2140 11 and and CC cord-014597-66vd2mdu 2140 12 more more RBR cord-014597-66vd2mdu 2140 13 effective effective JJ cord-014597-66vd2mdu 2140 14 drugs drug NNS cord-014597-66vd2mdu 2140 15 to to TO cord-014597-66vd2mdu 2140 16 treat treat VB cord-014597-66vd2mdu 2140 17 breast breast NN cord-014597-66vd2mdu 2140 18 cancer cancer NN cord-014597-66vd2mdu 2140 19 . . . cord-014597-66vd2mdu 2141 1 Notch notch NN cord-014597-66vd2mdu 2141 2 signaling signaling NN cord-014597-66vd2mdu 2141 3 is be VBZ cord-014597-66vd2mdu 2141 4 an an DT cord-014597-66vd2mdu 2141 5 evolutionary evolutionary JJ cord-014597-66vd2mdu 2141 6 conserved conserved JJ cord-014597-66vd2mdu 2141 7 cell cell NN cord-014597-66vd2mdu 2141 8 - - HYPH cord-014597-66vd2mdu 2141 9 to to IN cord-014597-66vd2mdu 2141 10 - - HYPH cord-014597-66vd2mdu 2141 11 cell cell NN cord-014597-66vd2mdu 2141 12 communication communication NN cord-014597-66vd2mdu 2141 13 pathway pathway NN cord-014597-66vd2mdu 2141 14 crucial crucial JJ cord-014597-66vd2mdu 2141 15 during during IN cord-014597-66vd2mdu 2141 16 embryonic embryonic JJ cord-014597-66vd2mdu 2141 17 and and CC cord-014597-66vd2mdu 2141 18 breast breast NN cord-014597-66vd2mdu 2141 19 development development NN cord-014597-66vd2mdu 2141 20 and and CC cord-014597-66vd2mdu 2141 21 tissue tissue NN cord-014597-66vd2mdu 2141 22 homeostasis homeostasis NN cord-014597-66vd2mdu 2141 23 . . . cord-014597-66vd2mdu 2142 1 This this DT cord-014597-66vd2mdu 2142 2 pathway pathway NN cord-014597-66vd2mdu 2142 3 is be VBZ cord-014597-66vd2mdu 2142 4 often often RB cord-014597-66vd2mdu 2142 5 hyper hyper RB cord-014597-66vd2mdu 2142 6 - - JJ cord-014597-66vd2mdu 2142 7 activated activate VBN cord-014597-66vd2mdu 2142 8 by by IN cord-014597-66vd2mdu 2142 9 overexpression overexpression NN cord-014597-66vd2mdu 2142 10 of of IN cord-014597-66vd2mdu 2142 11 Notch notch NN cord-014597-66vd2mdu 2142 12 receptors receptor NNS cord-014597-66vd2mdu 2142 13 and/or and/or CC cord-014597-66vd2mdu 2142 14 its -PRON- PRP$ cord-014597-66vd2mdu 2142 15 ligands ligand NNS cord-014597-66vd2mdu 2142 16 in in IN cord-014597-66vd2mdu 2142 17 several several JJ cord-014597-66vd2mdu 2142 18 types type NNS cord-014597-66vd2mdu 2142 19 of of IN cord-014597-66vd2mdu 2142 20 cancers cancer NNS cord-014597-66vd2mdu 2142 21 , , , cord-014597-66vd2mdu 2142 22 such such JJ cord-014597-66vd2mdu 2142 23 as as IN cord-014597-66vd2mdu 2142 24 breast breast NN cord-014597-66vd2mdu 2142 25 cancer cancer NN cord-014597-66vd2mdu 2142 26 ( ( -LRB- cord-014597-66vd2mdu 2142 27 TNBC TNBC NNP cord-014597-66vd2mdu 2142 28 included include VBD cord-014597-66vd2mdu 2142 29 ) ) -RRB- cord-014597-66vd2mdu 2142 30 , , , cord-014597-66vd2mdu 2142 31 where where WRB cord-014597-66vd2mdu 2142 32 it -PRON- PRP cord-014597-66vd2mdu 2142 33 contributes contribute VBZ cord-014597-66vd2mdu 2142 34 to to IN cord-014597-66vd2mdu 2142 35 its -PRON- PRP$ cord-014597-66vd2mdu 2142 36 development development NN cord-014597-66vd2mdu 2142 37 , , , cord-014597-66vd2mdu 2142 38 progression progression NN cord-014597-66vd2mdu 2142 39 and and CC cord-014597-66vd2mdu 2142 40 drug drug NN cord-014597-66vd2mdu 2142 41 resistance resistance NN cord-014597-66vd2mdu 2142 42 [ [ -LRB- cord-014597-66vd2mdu 2142 43 3 3 CD cord-014597-66vd2mdu 2142 44 ] ] -RRB- cord-014597-66vd2mdu 2142 45 , , , cord-014597-66vd2mdu 2142 46 [ [ -LRB- cord-014597-66vd2mdu 2142 47 4 4 CD cord-014597-66vd2mdu 2142 48 ] ] -RRB- cord-014597-66vd2mdu 2142 49 , , , cord-014597-66vd2mdu 2142 50 [ [ -LRB- cord-014597-66vd2mdu 2142 51 5 5 CD cord-014597-66vd2mdu 2142 52 ] ] -RRB- cord-014597-66vd2mdu 2142 53 . . . cord-014597-66vd2mdu 2143 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2143 2 aim aim NN cord-014597-66vd2mdu 2143 3 is be VBZ cord-014597-66vd2mdu 2143 4 to to TO cord-014597-66vd2mdu 2143 5 generate generate VB cord-014597-66vd2mdu 2143 6 a a DT cord-014597-66vd2mdu 2143 7 function function NN cord-014597-66vd2mdu 2143 8 blocking block VBG cord-014597-66vd2mdu 2143 9 antibody antibody NN cord-014597-66vd2mdu 2143 10 against against IN cord-014597-66vd2mdu 2143 11 the the DT cord-014597-66vd2mdu 2143 12 Notch Notch NNP cord-014597-66vd2mdu 2143 13 Delta Delta NNP cord-014597-66vd2mdu 2143 14 - - HYPH cord-014597-66vd2mdu 2143 15 like-1 like-1 NNP cord-014597-66vd2mdu 2143 16 ( ( -LRB- cord-014597-66vd2mdu 2143 17 DLL1 DLL1 NNP cord-014597-66vd2mdu 2143 18 ) ) -RRB- cord-014597-66vd2mdu 2143 19 ligand ligand NN cord-014597-66vd2mdu 2143 20 with with IN cord-014597-66vd2mdu 2143 21 therapeutic therapeutic JJ cord-014597-66vd2mdu 2143 22 efficacy efficacy NN cord-014597-66vd2mdu 2143 23 against against IN cord-014597-66vd2mdu 2143 24 breast breast NN cord-014597-66vd2mdu 2143 25 cancer cancer NN cord-014597-66vd2mdu 2143 26 . . . cord-014597-66vd2mdu 2144 1 Materials material NNS cord-014597-66vd2mdu 2144 2 and and CC cord-014597-66vd2mdu 2144 3 methods method NNS cord-014597-66vd2mdu 2144 4 DNA dna NN cord-014597-66vd2mdu 2144 5 of of IN cord-014597-66vd2mdu 2144 6 human human JJ cord-014597-66vd2mdu 2144 7 DLL1 DLL1 NNP cord-014597-66vd2mdu 2144 8 full full JJ cord-014597-66vd2mdu 2144 9 length length NN cord-014597-66vd2mdu 2144 10 extracellular extracellular JJ cord-014597-66vd2mdu 2144 11 domain domain NN cord-014597-66vd2mdu 2144 12 ( ( -LRB- cord-014597-66vd2mdu 2144 13 DLL1-ECD DLL1-ECD NNP cord-014597-66vd2mdu 2144 14 ) ) -RRB- cord-014597-66vd2mdu 2144 15 and and CC cord-014597-66vd2mdu 2144 16 a a DT cord-014597-66vd2mdu 2144 17 truncated truncated JJ cord-014597-66vd2mdu 2144 18 version version NN cord-014597-66vd2mdu 2144 19 , , , cord-014597-66vd2mdu 2144 20 containing contain VBG cord-014597-66vd2mdu 2144 21 the the DT cord-014597-66vd2mdu 2144 22 minimal minimal JJ cord-014597-66vd2mdu 2144 23 binding bind VBG cord-014597-66vd2mdu 2144 24 region region NN cord-014597-66vd2mdu 2144 25 to to IN cord-014597-66vd2mdu 2144 26 the the DT cord-014597-66vd2mdu 2144 27 Notch Notch NNP cord-014597-66vd2mdu 2144 28 receptor receptor NN cord-014597-66vd2mdu 2144 29 ( ( -LRB- cord-014597-66vd2mdu 2144 30 DLL1-EGF3 DLL1-EGF3 NNP cord-014597-66vd2mdu 2144 31 ) ) -RRB- cord-014597-66vd2mdu 2144 32 , , , cord-014597-66vd2mdu 2144 33 were be VBD cord-014597-66vd2mdu 2144 34 cloned clone VBN cord-014597-66vd2mdu 2144 35 into into IN cord-014597-66vd2mdu 2144 36 pFUSE pfuse NN cord-014597-66vd2mdu 2144 37 - - HYPH cord-014597-66vd2mdu 2144 38 Fc1-IgG1 fc1-igg1 NN cord-014597-66vd2mdu 2144 39 , , , cord-014597-66vd2mdu 2144 40 and and CC cord-014597-66vd2mdu 2144 41 expressed express VBD cord-014597-66vd2mdu 2144 42 in in IN cord-014597-66vd2mdu 2144 43 HEK293E6cells hek293e6cell NNS cord-014597-66vd2mdu 2144 44 . . . cord-014597-66vd2mdu 2145 1 Recombinant recombinant JJ cord-014597-66vd2mdu 2145 2 proteins protein NNS cord-014597-66vd2mdu 2145 3 were be VBD cord-014597-66vd2mdu 2145 4 purified purify VBN cord-014597-66vd2mdu 2145 5 from from IN cord-014597-66vd2mdu 2145 6 culture culture NN cord-014597-66vd2mdu 2145 7 media medium NNS cord-014597-66vd2mdu 2145 8 by by IN cord-014597-66vd2mdu 2145 9 Protein Protein NNP cord-014597-66vd2mdu 2145 10 - - HYPH cord-014597-66vd2mdu 2145 11 A a DT cord-014597-66vd2mdu 2145 12 affinity affinity NN cord-014597-66vd2mdu 2145 13 and and CC cord-014597-66vd2mdu 2145 14 size size NN cord-014597-66vd2mdu 2145 15 exclusion exclusion NN cord-014597-66vd2mdu 2145 16 chromatography chromatography NN cord-014597-66vd2mdu 2145 17 . . . cord-014597-66vd2mdu 2146 1 The the DT cord-014597-66vd2mdu 2146 2 human human JJ cord-014597-66vd2mdu 2146 3 scFv scFv HYPH cord-014597-66vd2mdu 2146 4 phage phage NN cord-014597-66vd2mdu 2146 5 display display NN cord-014597-66vd2mdu 2147 1 Tomlinson Tomlinson NNP cord-014597-66vd2mdu 2147 2 I+J I+J NNP cord-014597-66vd2mdu 2147 3 library library NN cord-014597-66vd2mdu 2147 4 was be VBD cord-014597-66vd2mdu 2147 5 used use VBN cord-014597-66vd2mdu 2147 6 to to TO cord-014597-66vd2mdu 2147 7 select select VB cord-014597-66vd2mdu 2147 8 specific specific JJ cord-014597-66vd2mdu 2147 9 scFv scfv NN cord-014597-66vd2mdu 2147 10 against against IN cord-014597-66vd2mdu 2147 11 peptides peptide NNS cord-014597-66vd2mdu 2147 12 targeting target VBG cord-014597-66vd2mdu 2147 13 DLL1 dll1 JJ cord-014597-66vd2mdu 2147 14 binding bind VBG cord-014597-66vd2mdu 2147 15 regions region NNS cord-014597-66vd2mdu 2147 16 to to IN cord-014597-66vd2mdu 2147 17 Notch notch NN cord-014597-66vd2mdu 2147 18 . . . cord-014597-66vd2mdu 2148 1 The the DT cord-014597-66vd2mdu 2148 2 binding bind VBG cord-014597-66vd2mdu 2148 3 ability ability NN cord-014597-66vd2mdu 2148 4 and and CC cord-014597-66vd2mdu 2148 5 specificity specificity NN cord-014597-66vd2mdu 2148 6 of of IN cord-014597-66vd2mdu 2148 7 the the DT cord-014597-66vd2mdu 2148 8 selected select VBN cord-014597-66vd2mdu 2148 9 scFv scfv JJ cord-014597-66vd2mdu 2148 10 clones clone NNS cord-014597-66vd2mdu 2148 11 was be VBD cord-014597-66vd2mdu 2148 12 evaluated evaluate VBN cord-014597-66vd2mdu 2148 13 by by IN cord-014597-66vd2mdu 2148 14 scFv scfv NN cord-014597-66vd2mdu 2148 15 - - HYPH cord-014597-66vd2mdu 2148 16 on on IN cord-014597-66vd2mdu 2148 17 - - HYPH cord-014597-66vd2mdu 2148 18 Phage phage NN cord-014597-66vd2mdu 2148 19 ELISA ELISA NNP cord-014597-66vd2mdu 2148 20 . . . cord-014597-66vd2mdu 2149 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2149 2 strategy strategy NN cord-014597-66vd2mdu 2149 3 allowed allow VBD cord-014597-66vd2mdu 2149 4 us -PRON- PRP cord-014597-66vd2mdu 2149 5 to to TO cord-014597-66vd2mdu 2149 6 obtain obtain VB cord-014597-66vd2mdu 2149 7 20 20 CD cord-014597-66vd2mdu 2149 8 mg mg NNS cord-014597-66vd2mdu 2149 9 of of IN cord-014597-66vd2mdu 2149 10 pure pure JJ cord-014597-66vd2mdu 2149 11 ( ( -LRB- cord-014597-66vd2mdu 2149 12 > > NFP cord-014597-66vd2mdu 2149 13 95 95 CD cord-014597-66vd2mdu 2149 14 % % NN cord-014597-66vd2mdu 2149 15 ) ) -RRB- cord-014597-66vd2mdu 2149 16 and and CC cord-014597-66vd2mdu 2149 17 stable stable JJ cord-014597-66vd2mdu 2149 18 DLL1-ECD DLL1-ECD NNP cord-014597-66vd2mdu 2149 19 - - HYPH cord-014597-66vd2mdu 2149 20 FC FC NNP cord-014597-66vd2mdu 2149 21 as as IN cord-014597-66vd2mdu 2149 22 confirmed confirm VBN cord-014597-66vd2mdu 2149 23 by by IN cord-014597-66vd2mdu 2149 24 SDS SDS NNP cord-014597-66vd2mdu 2149 25 PAGE PAGE NNP cord-014597-66vd2mdu 2149 26 and and CC cord-014597-66vd2mdu 2149 27 thermofluor thermofluor NNP cord-014597-66vd2mdu 2149 28 assay assay NN cord-014597-66vd2mdu 2149 29 . . . cord-014597-66vd2mdu 2150 1 DLL1-EGF3-FC dll1-egf3-fc JJ cord-014597-66vd2mdu 2150 2 yield yield NN cord-014597-66vd2mdu 2150 3 was be VBD cord-014597-66vd2mdu 2150 4 very very RB cord-014597-66vd2mdu 2150 5 low low JJ cord-014597-66vd2mdu 2150 6 and and CC cord-014597-66vd2mdu 2150 7 buffer buffer NN cord-014597-66vd2mdu 2150 8 screenings screening NNS cord-014597-66vd2mdu 2150 9 are be VBP cord-014597-66vd2mdu 2150 10 ongoing ongoing JJ cord-014597-66vd2mdu 2150 11 to to TO cord-014597-66vd2mdu 2150 12 optimize optimize VB cord-014597-66vd2mdu 2150 13 protein protein NN cord-014597-66vd2mdu 2150 14 stability stability NN cord-014597-66vd2mdu 2150 15 . . . cord-014597-66vd2mdu 2151 1 Functional functional JJ cord-014597-66vd2mdu 2151 2 studies study NNS cord-014597-66vd2mdu 2151 3 performed perform VBN cord-014597-66vd2mdu 2151 4 in in IN cord-014597-66vd2mdu 2151 5 human human JJ cord-014597-66vd2mdu 2151 6 breast breast NN cord-014597-66vd2mdu 2151 7 cancer cancer NN cord-014597-66vd2mdu 2152 1 MCF7 MCF7 NNP cord-014597-66vd2mdu 2152 2 cells cell NNS cord-014597-66vd2mdu 2152 3 showed show VBD cord-014597-66vd2mdu 2152 4 that that IN cord-014597-66vd2mdu 2152 5 both both DT cord-014597-66vd2mdu 2152 6 ligands ligand NNS cord-014597-66vd2mdu 2152 7 are be VBP cord-014597-66vd2mdu 2152 8 biologically biologically RB cord-014597-66vd2mdu 2152 9 active active JJ cord-014597-66vd2mdu 2152 10 as as IN cord-014597-66vd2mdu 2152 11 they -PRON- PRP cord-014597-66vd2mdu 2152 12 increased increase VBD cord-014597-66vd2mdu 2152 13 the the DT cord-014597-66vd2mdu 2152 14 expression expression NN cord-014597-66vd2mdu 2152 15 of of IN cord-014597-66vd2mdu 2152 16 the the DT cord-014597-66vd2mdu 2152 17 Notch notch NN cord-014597-66vd2mdu 2152 18 - - HYPH cord-014597-66vd2mdu 2152 19 dependent dependent JJ cord-014597-66vd2mdu 2152 20 genes gene NNS cord-014597-66vd2mdu 2152 21 HES-1 HES-1 NNP cord-014597-66vd2mdu 2152 22 , , , cord-014597-66vd2mdu 2152 23 HEY HEY NNP cord-014597-66vd2mdu 2152 24 - - HYPH cord-014597-66vd2mdu 2152 25 L l NN cord-014597-66vd2mdu 2152 26 and and CC cord-014597-66vd2mdu 2152 27 HEY-1 hey-1 RB cord-014597-66vd2mdu 2152 28 . . . cord-014597-66vd2mdu 2153 1 Recombinant recombinant JJ cord-014597-66vd2mdu 2153 2 DLL1 DLL1 NNP cord-014597-66vd2mdu 2153 3 and and CC cord-014597-66vd2mdu 2153 4 peptides peptide NNS cord-014597-66vd2mdu 2153 5 were be VBD cord-014597-66vd2mdu 2153 6 used use VBN cord-014597-66vd2mdu 2153 7 to to TO cord-014597-66vd2mdu 2153 8 select select VB cord-014597-66vd2mdu 2153 9 for for IN cord-014597-66vd2mdu 2153 10 monoclonal monoclonal JJ cord-014597-66vd2mdu 2153 11 antibodies antibody NNS cord-014597-66vd2mdu 2153 12 by by IN cord-014597-66vd2mdu 2153 13 Phage Phage NNP cord-014597-66vd2mdu 2153 14 Display Display NNP cord-014597-66vd2mdu 2153 15 . . . cord-014597-66vd2mdu 2154 1 After after IN cord-014597-66vd2mdu 2154 2 three three CD cord-014597-66vd2mdu 2154 3 rounds round NNS cord-014597-66vd2mdu 2154 4 of of IN cord-014597-66vd2mdu 2154 5 panning pan VBG cord-014597-66vd2mdu 2154 6 with with IN cord-014597-66vd2mdu 2154 7 DLL1 DLL1 NNP cord-014597-66vd2mdu 2154 8 peptides peptide NNS cord-014597-66vd2mdu 2154 9 we -PRON- PRP cord-014597-66vd2mdu 2154 10 identified identify VBD cord-014597-66vd2mdu 2154 11 13 13 CD cord-014597-66vd2mdu 2154 12 scFv scfv JJ cord-014597-66vd2mdu 2154 13 positive positive JJ cord-014597-66vd2mdu 2154 14 clones clone NNS cord-014597-66vd2mdu 2154 15 , , , cord-014597-66vd2mdu 2154 16 2 2 CD cord-014597-66vd2mdu 2154 17 of of IN cord-014597-66vd2mdu 2154 18 which which WDT cord-014597-66vd2mdu 2154 19 presented present VBD cord-014597-66vd2mdu 2154 20 high high JJ cord-014597-66vd2mdu 2154 21 affinity affinity NN cord-014597-66vd2mdu 2154 22 to to IN cord-014597-66vd2mdu 2154 23 DLL1-ECD DLL1-ECD NNP cord-014597-66vd2mdu 2154 24 - - HYPH cord-014597-66vd2mdu 2154 25 FC FC NNP cord-014597-66vd2mdu 2154 26 . . . cord-014597-66vd2mdu 2155 1 Currently currently RB cord-014597-66vd2mdu 2155 2 we -PRON- PRP cord-014597-66vd2mdu 2155 3 are be VBP cord-014597-66vd2mdu 2155 4 performing perform VBG cord-014597-66vd2mdu 2155 5 more more JJR cord-014597-66vd2mdu 2155 6 phage phage NN cord-014597-66vd2mdu 2155 7 display display NN cord-014597-66vd2mdu 2155 8 selections selection NNS cord-014597-66vd2mdu 2155 9 to to TO cord-014597-66vd2mdu 2155 10 increase increase VB cord-014597-66vd2mdu 2155 11 the the DT cord-014597-66vd2mdu 2155 12 number number NN cord-014597-66vd2mdu 2155 13 of of IN cord-014597-66vd2mdu 2155 14 positive positive JJ cord-014597-66vd2mdu 2155 15 clones clone NNS cord-014597-66vd2mdu 2155 16 . . . cord-014597-66vd2mdu 2156 1 scFv scFv NNP cord-014597-66vd2mdu 2156 2 with with IN cord-014597-66vd2mdu 2156 3 higher high JJR cord-014597-66vd2mdu 2156 4 affinities affinity NNS cord-014597-66vd2mdu 2156 5 will will MD cord-014597-66vd2mdu 2156 6 be be VB cord-014597-66vd2mdu 2156 7 reformatted reformatte VBN cord-014597-66vd2mdu 2156 8 into into IN cord-014597-66vd2mdu 2156 9 IgGs IgGs NNP cord-014597-66vd2mdu 2156 10 and and CC cord-014597-66vd2mdu 2156 11 their -PRON- PRP$ cord-014597-66vd2mdu 2156 12 ability ability NN cord-014597-66vd2mdu 2156 13 to to TO cord-014597-66vd2mdu 2156 14 inhibit inhibit VB cord-014597-66vd2mdu 2156 15 the the DT cord-014597-66vd2mdu 2156 16 Notch Notch NNP cord-014597-66vd2mdu 2156 17 pathway pathway NN cord-014597-66vd2mdu 2156 18 will will MD cord-014597-66vd2mdu 2156 19 be be VB cord-014597-66vd2mdu 2156 20 evaluated evaluate VBN cord-014597-66vd2mdu 2156 21 . . . cord-014597-66vd2mdu 2157 1 The the DT cord-014597-66vd2mdu 2157 2 anti anti JJ cord-014597-66vd2mdu 2157 3 - - JJ cord-014597-66vd2mdu 2157 4 oncogenic oncogenic JJ cord-014597-66vd2mdu 2157 5 effects effect NNS cord-014597-66vd2mdu 2157 6 of of IN cord-014597-66vd2mdu 2157 7 anti anti JJ cord-014597-66vd2mdu 2157 8 - - JJ cord-014597-66vd2mdu 2157 9 DLL1 dll1 JJ cord-014597-66vd2mdu 2157 10 IgGs iggs NN cord-014597-66vd2mdu 2157 11 will will MD cord-014597-66vd2mdu 2157 12 be be VB cord-014597-66vd2mdu 2157 13 assessed assess VBN cord-014597-66vd2mdu 2157 14 in in IN cord-014597-66vd2mdu 2157 15 breast breast NN cord-014597-66vd2mdu 2157 16 cancer cancer NN cord-014597-66vd2mdu 2157 17 cells cell NNS cord-014597-66vd2mdu 2157 18 in in IN cord-014597-66vd2mdu 2157 19 viability viability NN cord-014597-66vd2mdu 2157 20 / / SYM cord-014597-66vd2mdu 2157 21 apoptosis apoptosis NN cord-014597-66vd2mdu 2157 22 , , , cord-014597-66vd2mdu 2157 23 proliferation proliferation NN cord-014597-66vd2mdu 2157 24 , , , cord-014597-66vd2mdu 2157 25 migration migration NN cord-014597-66vd2mdu 2157 26 , , , cord-014597-66vd2mdu 2157 27 and and CC cord-014597-66vd2mdu 2157 28 invasion invasion NN cord-014597-66vd2mdu 2157 29 assays assay NNS cord-014597-66vd2mdu 2157 30 . . . cord-014597-66vd2mdu 2158 1 An an DT cord-014597-66vd2mdu 2158 2 anti anti JJ cord-014597-66vd2mdu 2158 3 - - JJ cord-014597-66vd2mdu 2158 4 DLL1 dll1 JJ cord-014597-66vd2mdu 2158 5 IgG igg NN cord-014597-66vd2mdu 2158 6 with with IN cord-014597-66vd2mdu 2158 7 therapeutic therapeutic JJ cord-014597-66vd2mdu 2158 8 efficacy efficacy NN cord-014597-66vd2mdu 2158 9 against against IN cord-014597-66vd2mdu 2158 10 breast breast NN cord-014597-66vd2mdu 2158 11 cancer cancer NN cord-014597-66vd2mdu 2158 12 will will MD cord-014597-66vd2mdu 2158 13 demonstrate demonstrate VB cord-014597-66vd2mdu 2158 14 that that IN cord-014597-66vd2mdu 2158 15 targeting target VBG cord-014597-66vd2mdu 2158 16 DLL1 DLL1 NNP cord-014597-66vd2mdu 2158 17 could could MD cord-014597-66vd2mdu 2158 18 be be VB cord-014597-66vd2mdu 2158 19 one one CD cord-014597-66vd2mdu 2158 20 of of IN cord-014597-66vd2mdu 2158 21 the the DT cord-014597-66vd2mdu 2158 22 key key JJ cord-014597-66vd2mdu 2158 23 factors factor NNS cord-014597-66vd2mdu 2158 24 for for IN cord-014597-66vd2mdu 2158 25 successfully successfully RB cord-014597-66vd2mdu 2158 26 targeting target VBG cord-014597-66vd2mdu 2158 27 breast breast NN cord-014597-66vd2mdu 2158 28 cancer cancer NN cord-014597-66vd2mdu 2158 29 . . . cord-014597-66vd2mdu 2159 1 Recombinant recombinant JJ cord-014597-66vd2mdu 2159 2 adeno adeno NN cord-014597-66vd2mdu 2159 3 - - HYPH cord-014597-66vd2mdu 2159 4 associated associate VBN cord-014597-66vd2mdu 2159 5 virus virus NN cord-014597-66vd2mdu 2159 6 ( ( -LRB- cord-014597-66vd2mdu 2159 7 rAAV rAAV NNP cord-014597-66vd2mdu 2159 8 ) ) -RRB- cord-014597-66vd2mdu 2159 9 approaches approach NNS cord-014597-66vd2mdu 2159 10 have have VBP cord-014597-66vd2mdu 2159 11 an an DT cord-014597-66vd2mdu 2159 12 outstanding outstanding JJ cord-014597-66vd2mdu 2159 13 reputation reputation NN cord-014597-66vd2mdu 2159 14 in in IN cord-014597-66vd2mdu 2159 15 gene gene NN cord-014597-66vd2mdu 2159 16 therapy therapy NN cord-014597-66vd2mdu 2159 17 and and CC cord-014597-66vd2mdu 2159 18 are be VBP cord-014597-66vd2mdu 2159 19 evaluated evaluate VBN cord-014597-66vd2mdu 2159 20 for for IN cord-014597-66vd2mdu 2159 21 cancer cancer NN cord-014597-66vd2mdu 2159 22 therapy therapy NN cord-014597-66vd2mdu 2159 23 [ [ -LRB- cord-014597-66vd2mdu 2159 24 1 1 CD cord-014597-66vd2mdu 2159 25 ] ] -RRB- cord-014597-66vd2mdu 2159 26 . . . cord-014597-66vd2mdu 2160 1 Advantages advantage NNS cord-014597-66vd2mdu 2160 2 include include VBP cord-014597-66vd2mdu 2160 3 long long JJ cord-014597-66vd2mdu 2160 4 - - HYPH cord-014597-66vd2mdu 2160 5 term term NN cord-014597-66vd2mdu 2160 6 gene gene NN cord-014597-66vd2mdu 2160 7 expression expression NN cord-014597-66vd2mdu 2160 8 , , , cord-014597-66vd2mdu 2160 9 targeting target VBG cord-014597-66vd2mdu 2160 10 of of IN cord-014597-66vd2mdu 2160 11 dividing divide VBG cord-014597-66vd2mdu 2160 12 and and CC cord-014597-66vd2mdu 2160 13 non non JJ cord-014597-66vd2mdu 2160 14 - - JJ cord-014597-66vd2mdu 2160 15 dividing dividing JJ cord-014597-66vd2mdu 2160 16 cells cell NNS cord-014597-66vd2mdu 2160 17 , , , cord-014597-66vd2mdu 2160 18 and and CC cord-014597-66vd2mdu 2160 19 low low JJ cord-014597-66vd2mdu 2160 20 immunogenicity immunogenicity NN cord-014597-66vd2mdu 2160 21 . . . cord-014597-66vd2mdu 2161 1 Established established JJ cord-014597-66vd2mdu 2161 2 rAAV raav NN cord-014597-66vd2mdu 2161 3 production production NN cord-014597-66vd2mdu 2161 4 utilizes utilize VBZ cord-014597-66vd2mdu 2161 5 triple triple JJ cord-014597-66vd2mdu 2161 6 transfection transfection NN cord-014597-66vd2mdu 2161 7 of of IN cord-014597-66vd2mdu 2161 8 adherent adherent JJ cord-014597-66vd2mdu 2161 9 HEK HEK NNP cord-014597-66vd2mdu 2161 10 293 293 CD cord-014597-66vd2mdu 2161 11 cells cell NNS cord-014597-66vd2mdu 2161 12 , , , cord-014597-66vd2mdu 2161 13 which which WDT cord-014597-66vd2mdu 2161 14 hardly hardly RB cord-014597-66vd2mdu 2161 15 meets meet VBZ cord-014597-66vd2mdu 2161 16 product product NN cord-014597-66vd2mdu 2161 17 yield yield NN cord-014597-66vd2mdu 2161 18 requirements requirement NNS cord-014597-66vd2mdu 2161 19 for for IN cord-014597-66vd2mdu 2161 20 clinical clinical JJ cord-014597-66vd2mdu 2161 21 applications application NNS cord-014597-66vd2mdu 2161 22 . . . cord-014597-66vd2mdu 2162 1 We -PRON- PRP cord-014597-66vd2mdu 2162 2 transferred transfer VBD cord-014597-66vd2mdu 2162 3 the the DT cord-014597-66vd2mdu 2162 4 AAV AAV NNP cord-014597-66vd2mdu 2162 5 production production NN cord-014597-66vd2mdu 2162 6 system system NN cord-014597-66vd2mdu 2162 7 to to IN cord-014597-66vd2mdu 2162 8 HEK HEK NNP cord-014597-66vd2mdu 2162 9 293-F 293-F NNP cord-014597-66vd2mdu 2162 10 suspension suspension NN cord-014597-66vd2mdu 2162 11 cells cell NNS cord-014597-66vd2mdu 2162 12 . . . cord-014597-66vd2mdu 2163 1 This this DT cord-014597-66vd2mdu 2163 2 process process NN cord-014597-66vd2mdu 2163 3 is be VBZ cord-014597-66vd2mdu 2163 4 scalable scalable JJ cord-014597-66vd2mdu 2163 5 and and CC cord-014597-66vd2mdu 2163 6 uses use VBZ cord-014597-66vd2mdu 2163 7 serum serum NN cord-014597-66vd2mdu 2163 8 - - HYPH cord-014597-66vd2mdu 2163 9 free free JJ cord-014597-66vd2mdu 2163 10 media medium NNS cord-014597-66vd2mdu 2163 11 streamlining streamline VBG cord-014597-66vd2mdu 2163 12 downstream downstream JJ cord-014597-66vd2mdu 2163 13 procedures procedure NNS cord-014597-66vd2mdu 2163 14 . . . cord-014597-66vd2mdu 2164 1 After after IN cord-014597-66vd2mdu 2164 2 optimization optimization NN cord-014597-66vd2mdu 2164 3 of of IN cord-014597-66vd2mdu 2164 4 transfection transfection NN cord-014597-66vd2mdu 2164 5 efficiencies efficiency NNS cord-014597-66vd2mdu 2164 6 and and CC cord-014597-66vd2mdu 2164 7 shaker shaker NN cord-014597-66vd2mdu 2164 8 cultivations cultivation NNS cord-014597-66vd2mdu 2164 9 , , , cord-014597-66vd2mdu 2164 10 we -PRON- PRP cord-014597-66vd2mdu 2164 11 produced produce VBD cord-014597-66vd2mdu 2164 12 titers titer NNS cord-014597-66vd2mdu 2164 13 of of IN cord-014597-66vd2mdu 2164 14 1×10 1×10 CD cord-014597-66vd2mdu 2164 15 5 5 CD cord-014597-66vd2mdu 2164 16 viral viral JJ cord-014597-66vd2mdu 2164 17 genomes genome NNS cord-014597-66vd2mdu 2164 18 per per IN cord-014597-66vd2mdu 2164 19 cell cell NN cord-014597-66vd2mdu 2164 20 in in IN cord-014597-66vd2mdu 2164 21 a a DT cord-014597-66vd2mdu 2164 22 2 2 CD cord-014597-66vd2mdu 2164 23 l l NN cord-014597-66vd2mdu 2164 24 bioreactor bioreactor NN cord-014597-66vd2mdu 2164 25 . . . cord-014597-66vd2mdu 2165 1 The the DT cord-014597-66vd2mdu 2165 2 suspension suspension NN cord-014597-66vd2mdu 2165 3 adapted adapt VBD cord-014597-66vd2mdu 2165 4 HEK HEK NNP cord-014597-66vd2mdu 2165 5 - - HYPH cord-014597-66vd2mdu 2165 6 FreeStyle FreeStyle NNP cord-014597-66vd2mdu 2165 7 293-F 293-f CD cord-014597-66vd2mdu 2165 8 cell cell NN cord-014597-66vd2mdu 2165 9 line line NN cord-014597-66vd2mdu 2165 10 was be VBD cord-014597-66vd2mdu 2165 11 used use VBN cord-014597-66vd2mdu 2165 12 for for IN cord-014597-66vd2mdu 2165 13 the the DT cord-014597-66vd2mdu 2165 14 experiments experiment NNS cord-014597-66vd2mdu 2165 15 in in IN cord-014597-66vd2mdu 2165 16 chemically chemically RB cord-014597-66vd2mdu 2165 17 defined define VBN cord-014597-66vd2mdu 2165 18 animal animal NN cord-014597-66vd2mdu 2165 19 component component NN cord-014597-66vd2mdu 2165 20 free free JJ cord-014597-66vd2mdu 2165 21 media medium NNS cord-014597-66vd2mdu 2165 22 ( ( -LRB- cord-014597-66vd2mdu 2165 23 HEK HEK NNP cord-014597-66vd2mdu 2165 24 - - HYPH cord-014597-66vd2mdu 2165 25 TF TF NNP cord-014597-66vd2mdu 2165 26 , , , cord-014597-66vd2mdu 2165 27 HEK HEK NNP cord-014597-66vd2mdu 2165 28 - - HYPH cord-014597-66vd2mdu 2165 29 GM GM NNP cord-014597-66vd2mdu 2165 30 ( ( -LRB- cord-014597-66vd2mdu 2165 31 Xell Xell NNP cord-014597-66vd2mdu 2165 32 AG AG NNP cord-014597-66vd2mdu 2165 33 ) ) -RRB- cord-014597-66vd2mdu 2165 34 , , , cord-014597-66vd2mdu 2165 35 Freestyle Freestyle NNP cord-014597-66vd2mdu 2165 36 F17 F17 NNP cord-014597-66vd2mdu 2165 37 ( ( -LRB- cord-014597-66vd2mdu 2165 38 Thermo Thermo NNP cord-014597-66vd2mdu 2165 39 Fisher Fisher NNP cord-014597-66vd2mdu 2165 40 Scientific Scientific NNP cord-014597-66vd2mdu 2165 41 ) ) -RRB- cord-014597-66vd2mdu 2165 42 ) ) -RRB- cord-014597-66vd2mdu 2165 43 . . . cord-014597-66vd2mdu 2166 1 Samples sample NNS cord-014597-66vd2mdu 2166 2 for for IN cord-014597-66vd2mdu 2166 3 viable viable JJ cord-014597-66vd2mdu 2166 4 cell cell NN cord-014597-66vd2mdu 2166 5 density density NN cord-014597-66vd2mdu 2166 6 and and CC cord-014597-66vd2mdu 2166 7 viabilities viability NNS cord-014597-66vd2mdu 2166 8 were be VBD cord-014597-66vd2mdu 2166 9 taken take VBN cord-014597-66vd2mdu 2166 10 daily daily RB cord-014597-66vd2mdu 2166 11 and and CC cord-014597-66vd2mdu 2166 12 analyzed analyze VBD cord-014597-66vd2mdu 2166 13 using use VBG cord-014597-66vd2mdu 2166 14 an an DT cord-014597-66vd2mdu 2166 15 automated automate VBN cord-014597-66vd2mdu 2166 16 cell cell NN cord-014597-66vd2mdu 2166 17 counting counting NN cord-014597-66vd2mdu 2166 18 system system NN cord-014597-66vd2mdu 2166 19 ( ( -LRB- cord-014597-66vd2mdu 2166 20 CEDEX CEDEX NNP cord-014597-66vd2mdu 2166 21 , , , cord-014597-66vd2mdu 2166 22 Roche Roche NNP cord-014597-66vd2mdu 2166 23 Diagnostics Diagnostics NNP cord-014597-66vd2mdu 2166 24 ) ) -RRB- cord-014597-66vd2mdu 2166 25 . . . cord-014597-66vd2mdu 2167 1 Transient transient JJ cord-014597-66vd2mdu 2167 2 transfection transfection NN cord-014597-66vd2mdu 2167 3 of of IN cord-014597-66vd2mdu 2167 4 3×10 3×10 CD cord-014597-66vd2mdu 2167 5 6 6 CD cord-014597-66vd2mdu 2167 6 cells cell NNS cord-014597-66vd2mdu 2167 7 / / SYM cord-014597-66vd2mdu 2167 8 ml ml NNS cord-014597-66vd2mdu 2167 9 was be VBD cord-014597-66vd2mdu 2167 10 carried carry VBN cord-014597-66vd2mdu 2167 11 out out RP cord-014597-66vd2mdu 2167 12 with with IN cord-014597-66vd2mdu 2167 13 polyethylenimine polyethylenimine NNP cord-014597-66vd2mdu 2167 14 Max Max NNP cord-014597-66vd2mdu 2167 15 in in IN cord-014597-66vd2mdu 2167 16 a a DT cord-014597-66vd2mdu 2167 17 1:4 1:4 CD cord-014597-66vd2mdu 2167 18 DNA DNA NNP cord-014597-66vd2mdu 2167 19 - - HYPH cord-014597-66vd2mdu 2167 20 PEI PEI NNP cord-014597-66vd2mdu 2167 21 ratio ratio NN cord-014597-66vd2mdu 2167 22 ( ( -LRB- cord-014597-66vd2mdu 2167 23 w w NNP cord-014597-66vd2mdu 2167 24 / / SYM cord-014597-66vd2mdu 2167 25 w w NN cord-014597-66vd2mdu 2167 26 ) ) -RRB- cord-014597-66vd2mdu 2167 27 with with IN cord-014597-66vd2mdu 2167 28 2 2 CD cord-014597-66vd2mdu 2167 29 μg μg NN cord-014597-66vd2mdu 2167 30 DNA DNA NNP cord-014597-66vd2mdu 2167 31 . . . cord-014597-66vd2mdu 2168 1 Three three CD cord-014597-66vd2mdu 2168 2 plasmids plasmid NNS cord-014597-66vd2mdu 2168 3 ( ( -LRB- cord-014597-66vd2mdu 2168 4 pGOI pgoi FW cord-014597-66vd2mdu 2168 5 , , , cord-014597-66vd2mdu 2168 6 pRepCap pRepCap NNP cord-014597-66vd2mdu 2168 7 , , , cord-014597-66vd2mdu 2168 8 pHelper pHelper NNP cord-014597-66vd2mdu 2168 9 ) ) -RRB- cord-014597-66vd2mdu 2168 10 were be VBD cord-014597-66vd2mdu 2168 11 applied apply VBN cord-014597-66vd2mdu 2168 12 in in IN cord-014597-66vd2mdu 2168 13 a a DT cord-014597-66vd2mdu 2168 14 molar molar JJ cord-014597-66vd2mdu 2168 15 1:1:1 1:1:1 CD cord-014597-66vd2mdu 2168 16 ratio ratio NN cord-014597-66vd2mdu 2168 17 ( ( -LRB- cord-014597-66vd2mdu 2168 18 Fig Fig NNP cord-014597-66vd2mdu 2168 19 . . . cord-014597-66vd2mdu 2168 20 1a 1a CD cord-014597-66vd2mdu 2168 21 ) ) -RRB- cord-014597-66vd2mdu 2168 22 . . . cord-014597-66vd2mdu 2169 1 Pretests pretest NNS cord-014597-66vd2mdu 2169 2 were be VBD cord-014597-66vd2mdu 2169 3 performed perform VBN cord-014597-66vd2mdu 2169 4 in in IN cord-014597-66vd2mdu 2169 5 orbital orbital JJ cord-014597-66vd2mdu 2169 6 shaking shake VBG cord-014597-66vd2mdu 2169 7 tube tube NN cord-014597-66vd2mdu 2169 8 spin spin NN cord-014597-66vd2mdu 2169 9 bioreactors bioreactor NNS cord-014597-66vd2mdu 2169 10 . . . cord-014597-66vd2mdu 2170 1 For for IN cord-014597-66vd2mdu 2170 2 scale scale NN cord-014597-66vd2mdu 2170 3 - - HYPH cord-014597-66vd2mdu 2170 4 up up RP cord-014597-66vd2mdu 2170 5 , , , cord-014597-66vd2mdu 2170 6 batch batch NN cord-014597-66vd2mdu 2170 7 processes process NNS cord-014597-66vd2mdu 2170 8 were be VBD cord-014597-66vd2mdu 2170 9 carried carry VBN cord-014597-66vd2mdu 2170 10 out out RP cord-014597-66vd2mdu 2170 11 in in IN cord-014597-66vd2mdu 2170 12 125 125 CD cord-014597-66vd2mdu 2170 13 ml ml NN cord-014597-66vd2mdu 2170 14 shake shake NN cord-014597-66vd2mdu 2170 15 flasks flask NNS cord-014597-66vd2mdu 2170 16 as as RB cord-014597-66vd2mdu 2170 17 well well RB cord-014597-66vd2mdu 2170 18 as as IN cord-014597-66vd2mdu 2170 19 in in IN cord-014597-66vd2mdu 2170 20 2 2 CD cord-014597-66vd2mdu 2170 21 l l NN cord-014597-66vd2mdu 2170 22 stirred stir VBD cord-014597-66vd2mdu 2170 23 bioreactors bioreactor NNS cord-014597-66vd2mdu 2170 24 at at IN cord-014597-66vd2mdu 2170 25 30 30 CD cord-014597-66vd2mdu 2170 26 % % NN cord-014597-66vd2mdu 2170 27 air air NN cord-014597-66vd2mdu 2170 28 saturation saturation NN cord-014597-66vd2mdu 2170 29 and and CC cord-014597-66vd2mdu 2170 30 pH ph NN cord-014597-66vd2mdu 2170 31 7.1 7.1 CD cord-014597-66vd2mdu 2170 32 . . . cord-014597-66vd2mdu 2171 1 Transfection transfection NN cord-014597-66vd2mdu 2171 2 efficiencies efficiency NNS cord-014597-66vd2mdu 2171 3 and and CC cord-014597-66vd2mdu 2171 4 rAAV raav NN cord-014597-66vd2mdu 2171 5 production production NN cord-014597-66vd2mdu 2171 6 were be VBD cord-014597-66vd2mdu 2171 7 quantified quantify VBN cord-014597-66vd2mdu 2171 8 by by IN cord-014597-66vd2mdu 2171 9 flow flow NN cord-014597-66vd2mdu 2171 10 cytometry cytometry NN cord-014597-66vd2mdu 2171 11 using use VBG cord-014597-66vd2mdu 2171 12 a a DT cord-014597-66vd2mdu 2171 13 GOI GOI NNP cord-014597-66vd2mdu 2171 14 coding code VBG cord-014597-66vd2mdu 2171 15 for for IN cord-014597-66vd2mdu 2171 16 a a DT cord-014597-66vd2mdu 2171 17 fluorescent fluorescent JJ cord-014597-66vd2mdu 2171 18 protein protein NN cord-014597-66vd2mdu 2171 19 and and CC cord-014597-66vd2mdu 2171 20 qPCR qpcr NN cord-014597-66vd2mdu 2171 21 of of IN cord-014597-66vd2mdu 2171 22 genomic genomic JJ cord-014597-66vd2mdu 2171 23 copies copy NNS cord-014597-66vd2mdu 2171 24 , , , cord-014597-66vd2mdu 2171 25 respectively respectively RB cord-014597-66vd2mdu 2171 26 . . . cord-014597-66vd2mdu 2172 1 By by IN cord-014597-66vd2mdu 2172 2 optimizing optimize VBG cord-014597-66vd2mdu 2172 3 the the DT cord-014597-66vd2mdu 2172 4 DNA dna NN cord-014597-66vd2mdu 2172 5 amount amount NN cord-014597-66vd2mdu 2172 6 for for IN cord-014597-66vd2mdu 2172 7 transfection transfection NN cord-014597-66vd2mdu 2172 8 of of IN cord-014597-66vd2mdu 2172 9 293-F 293-f CD cord-014597-66vd2mdu 2172 10 cells cell NNS cord-014597-66vd2mdu 2172 11 more more JJR cord-014597-66vd2mdu 2172 12 than than IN cord-014597-66vd2mdu 2172 13 90 90 CD cord-014597-66vd2mdu 2172 14 % % NN cord-014597-66vd2mdu 2172 15 of of IN cord-014597-66vd2mdu 2172 16 the the DT cord-014597-66vd2mdu 2172 17 cells cell NNS cord-014597-66vd2mdu 2172 18 were be VBD cord-014597-66vd2mdu 2172 19 reproducibly reproducibly RB cord-014597-66vd2mdu 2172 20 transfected transfecte VBN cord-014597-66vd2mdu 2172 21 . . . cord-014597-66vd2mdu 2173 1 Batch batch NN cord-014597-66vd2mdu 2173 2 cultivations cultivation NNS cord-014597-66vd2mdu 2173 3 in in IN cord-014597-66vd2mdu 2173 4 shaker shaker NN cord-014597-66vd2mdu 2173 5 flasks flask NNS cord-014597-66vd2mdu 2173 6 revealed reveal VBD cord-014597-66vd2mdu 2173 7 that that IN cord-014597-66vd2mdu 2173 8 rAAV rAAV NNP cord-014597-66vd2mdu 2173 9 were be VBD cord-014597-66vd2mdu 2173 10 produced produce VBN cord-014597-66vd2mdu 2173 11 in in IN cord-014597-66vd2mdu 2173 12 the the DT cord-014597-66vd2mdu 2173 13 first first JJ cord-014597-66vd2mdu 2173 14 24 24 CD cord-014597-66vd2mdu 2173 15 - - SYM cord-014597-66vd2mdu 2173 16 96 96 CD cord-014597-66vd2mdu 2173 17 h h NN cord-014597-66vd2mdu 2173 18 after after IN cord-014597-66vd2mdu 2173 19 transfection transfection NN cord-014597-66vd2mdu 2173 20 . . . cord-014597-66vd2mdu 2174 1 Figure figure NN cord-014597-66vd2mdu 2174 2 1b 1b CD cord-014597-66vd2mdu 2174 3 shows show VBZ cord-014597-66vd2mdu 2174 4 viable viable JJ cord-014597-66vd2mdu 2174 5 cell cell NN cord-014597-66vd2mdu 2174 6 densities density NNS cord-014597-66vd2mdu 2174 7 and and CC cord-014597-66vd2mdu 2174 8 viabilities viability NNS cord-014597-66vd2mdu 2174 9 in in IN cord-014597-66vd2mdu 2174 10 relation relation NN cord-014597-66vd2mdu 2174 11 to to IN cord-014597-66vd2mdu 2174 12 the the DT cord-014597-66vd2mdu 2174 13 genomic genomic JJ cord-014597-66vd2mdu 2174 14 titer titer NN cord-014597-66vd2mdu 2174 15 . . . cord-014597-66vd2mdu 2175 1 Genomic genomic JJ cord-014597-66vd2mdu 2175 2 titers titer NNS cord-014597-66vd2mdu 2175 3 were be VBD cord-014597-66vd2mdu 2175 4 determined determine VBN cord-014597-66vd2mdu 2175 5 from from IN cord-014597-66vd2mdu 2175 6 raw raw JJ cord-014597-66vd2mdu 2175 7 cell cell NN cord-014597-66vd2mdu 2175 8 extracts extract NNS cord-014597-66vd2mdu 2175 9 and and CC cord-014597-66vd2mdu 2175 10 up up IN cord-014597-66vd2mdu 2175 11 to to TO cord-014597-66vd2mdu 2175 12 10 10 CD cord-014597-66vd2mdu 2175 13 9 9 CD cord-014597-66vd2mdu 2175 14 copies copy NNS cord-014597-66vd2mdu 2175 15 / / SYM cord-014597-66vd2mdu 2175 16 ml ml NNS cord-014597-66vd2mdu 2175 17 were be VBD cord-014597-66vd2mdu 2175 18 repetitively repetitively RB cord-014597-66vd2mdu 2175 19 achievable achievable JJ cord-014597-66vd2mdu 2175 20 . . . cord-014597-66vd2mdu 2176 1 A a DT cord-014597-66vd2mdu 2176 2 decrease decrease NN cord-014597-66vd2mdu 2176 3 in in IN cord-014597-66vd2mdu 2176 4 viability viability NN cord-014597-66vd2mdu 2176 5 marked mark VBD cord-014597-66vd2mdu 2176 6 the the DT cord-014597-66vd2mdu 2176 7 decline decline NN cord-014597-66vd2mdu 2176 8 in in IN cord-014597-66vd2mdu 2176 9 genomic genomic JJ cord-014597-66vd2mdu 2176 10 copies copy NNS cord-014597-66vd2mdu 2176 11 per per IN cord-014597-66vd2mdu 2176 12 ml ml NN cord-014597-66vd2mdu 2176 13 showing show VBG cord-014597-66vd2mdu 2176 14 that that IN cord-014597-66vd2mdu 2176 15 a a DT cord-014597-66vd2mdu 2176 16 prolongation prolongation NN cord-014597-66vd2mdu 2176 17 of of IN cord-014597-66vd2mdu 2176 18 the the DT cord-014597-66vd2mdu 2176 19 process process NN cord-014597-66vd2mdu 2176 20 e.g. e.g. RB cord-014597-66vd2mdu 2176 21 by by IN cord-014597-66vd2mdu 2176 22 addition addition NN cord-014597-66vd2mdu 2176 23 of of IN cord-014597-66vd2mdu 2176 24 a a DT cord-014597-66vd2mdu 2176 25 feed feed NN cord-014597-66vd2mdu 2176 26 would would MD cord-014597-66vd2mdu 2176 27 probably probably RB cord-014597-66vd2mdu 2176 28 not not RB cord-014597-66vd2mdu 2176 29 increase increase VB cord-014597-66vd2mdu 2176 30 yield yield NN cord-014597-66vd2mdu 2176 31 . . . cord-014597-66vd2mdu 2177 1 In in IN cord-014597-66vd2mdu 2177 2 a a DT cord-014597-66vd2mdu 2177 3 first first JJ cord-014597-66vd2mdu 2177 4 scale scale NN cord-014597-66vd2mdu 2177 5 - - HYPH cord-014597-66vd2mdu 2177 6 up up NN cord-014597-66vd2mdu 2177 7 , , , cord-014597-66vd2mdu 2177 8 the the DT cord-014597-66vd2mdu 2177 9 rAAV rAAV NNP cord-014597-66vd2mdu 2177 10 production production NN cord-014597-66vd2mdu 2177 11 was be VBD cord-014597-66vd2mdu 2177 12 transferred transfer VBN cord-014597-66vd2mdu 2177 13 to to IN cord-014597-66vd2mdu 2177 14 a a DT cord-014597-66vd2mdu 2177 15 2 2 CD cord-014597-66vd2mdu 2177 16 l l NN cord-014597-66vd2mdu 2177 17 bioreactor bioreactor NN cord-014597-66vd2mdu 2177 18 ( ( -LRB- cord-014597-66vd2mdu 2177 19 Fig Fig NNP cord-014597-66vd2mdu 2177 20 . . . cord-014597-66vd2mdu 2177 21 1c 1c CD cord-014597-66vd2mdu 2177 22 ) ) -RRB- cord-014597-66vd2mdu 2177 23 . . . cord-014597-66vd2mdu 2178 1 Transfection transfection NN cord-014597-66vd2mdu 2178 2 efficiencies efficiency NNS cord-014597-66vd2mdu 2178 3 in in IN cord-014597-66vd2mdu 2178 4 bioreactors bioreactor NNS cord-014597-66vd2mdu 2178 5 of of IN cord-014597-66vd2mdu 2178 6 up up IN cord-014597-66vd2mdu 2178 7 to to TO cord-014597-66vd2mdu 2178 8 55 55 CD cord-014597-66vd2mdu 2178 9 % % NN cord-014597-66vd2mdu 2178 10 were be VBD cord-014597-66vd2mdu 2178 11 comparable comparable JJ cord-014597-66vd2mdu 2178 12 to to IN cord-014597-66vd2mdu 2178 13 that that DT cord-014597-66vd2mdu 2178 14 obtained obtain VBN cord-014597-66vd2mdu 2178 15 in in IN cord-014597-66vd2mdu 2178 16 a a DT cord-014597-66vd2mdu 2178 17 simultaneous simultaneous JJ cord-014597-66vd2mdu 2178 18 shaker shaker NN cord-014597-66vd2mdu 2178 19 flask flask NN cord-014597-66vd2mdu 2178 20 experiment experiment NN cord-014597-66vd2mdu 2178 21 . . . cord-014597-66vd2mdu 2179 1 Transfection transfection NN cord-014597-66vd2mdu 2179 2 efficiencies efficiency NNS cord-014597-66vd2mdu 2179 3 were be VBD cord-014597-66vd2mdu 2179 4 lower low JJR cord-014597-66vd2mdu 2179 5 compared compare VBN cord-014597-66vd2mdu 2179 6 to to IN cord-014597-66vd2mdu 2179 7 prior prior JJ cord-014597-66vd2mdu 2179 8 experiments experiment NNS cord-014597-66vd2mdu 2179 9 due due JJ cord-014597-66vd2mdu 2179 10 to to IN cord-014597-66vd2mdu 2179 11 controlled control VBN cord-014597-66vd2mdu 2179 12 conditions condition NNS cord-014597-66vd2mdu 2179 13 in in IN cord-014597-66vd2mdu 2179 14 the the DT cord-014597-66vd2mdu 2179 15 bioreactor bioreactor NN cord-014597-66vd2mdu 2179 16 . . . cord-014597-66vd2mdu 2180 1 Nonetheless nonetheless RB cord-014597-66vd2mdu 2180 2 the the DT cord-014597-66vd2mdu 2180 3 titer titer NN cord-014597-66vd2mdu 2180 4 with with IN cord-014597-66vd2mdu 2180 5 up up IN cord-014597-66vd2mdu 2180 6 to to TO cord-014597-66vd2mdu 2180 7 1×10 1×10 CD cord-014597-66vd2mdu 2180 8 5 5 CD cord-014597-66vd2mdu 2180 9 genomic genomic JJ cord-014597-66vd2mdu 2180 10 copies copy NNS cord-014597-66vd2mdu 2180 11 per per IN cord-014597-66vd2mdu 2180 12 cell cell NN cord-014597-66vd2mdu 2180 13 was be VBD cord-014597-66vd2mdu 2180 14 elevated elevate VBN cord-014597-66vd2mdu 2180 15 compared compare VBN cord-014597-66vd2mdu 2180 16 to to IN cord-014597-66vd2mdu 2180 17 that that DT cord-014597-66vd2mdu 2180 18 of of IN cord-014597-66vd2mdu 2180 19 shaker shaker NN cord-014597-66vd2mdu 2180 20 flasks flask NNS cord-014597-66vd2mdu 2180 21 . . . cord-014597-66vd2mdu 2181 1 First first JJ cord-014597-66vd2mdu 2181 2 experiments experiment NNS cord-014597-66vd2mdu 2181 3 with with IN cord-014597-66vd2mdu 2181 4 293-F 293-f CD cord-014597-66vd2mdu 2181 5 cells cell NNS cord-014597-66vd2mdu 2181 6 in in IN cord-014597-66vd2mdu 2181 7 HEK HEK NNP cord-014597-66vd2mdu 2181 8 TF TF NNP cord-014597-66vd2mdu 2181 9 medium medium NN cord-014597-66vd2mdu 2181 10 showed show VBD cord-014597-66vd2mdu 2181 11 promising promising JJ cord-014597-66vd2mdu 2181 12 results result NNS cord-014597-66vd2mdu 2181 13 of of IN cord-014597-66vd2mdu 2181 14 transferring transfer VBG cord-014597-66vd2mdu 2181 15 rAAV raav NN cord-014597-66vd2mdu 2181 16 production production NN cord-014597-66vd2mdu 2181 17 from from IN cord-014597-66vd2mdu 2181 18 the the DT cord-014597-66vd2mdu 2181 19 adherent adherent JJ cord-014597-66vd2mdu 2181 20 system system NN cord-014597-66vd2mdu 2181 21 to to IN cord-014597-66vd2mdu 2181 22 suspension suspension NN cord-014597-66vd2mdu 2181 23 . . . cord-014597-66vd2mdu 2182 1 After after IN cord-014597-66vd2mdu 2182 2 improvement improvement NN cord-014597-66vd2mdu 2182 3 of of IN cord-014597-66vd2mdu 2182 4 transfections transfection NNS cord-014597-66vd2mdu 2182 5 by by IN cord-014597-66vd2mdu 2182 6 the the DT cord-014597-66vd2mdu 2182 7 adjustment adjustment NN cord-014597-66vd2mdu 2182 8 of of IN cord-014597-66vd2mdu 2182 9 DNA dna NN cord-014597-66vd2mdu 2182 10 amounts amount NNS cord-014597-66vd2mdu 2182 11 in in IN cord-014597-66vd2mdu 2182 12 small small JJ cord-014597-66vd2mdu 2182 13 scale scale NN cord-014597-66vd2mdu 2182 14 experiments experiment NNS cord-014597-66vd2mdu 2182 15 , , , cord-014597-66vd2mdu 2182 16 AAV AAV NNP cord-014597-66vd2mdu 2182 17 production production NN cord-014597-66vd2mdu 2182 18 was be VBD cord-014597-66vd2mdu 2182 19 analyzed analyze VBN cord-014597-66vd2mdu 2182 20 in in IN cord-014597-66vd2mdu 2182 21 shaker shaker NN cord-014597-66vd2mdu 2182 22 flasks flask NNS cord-014597-66vd2mdu 2182 23 . . . cord-014597-66vd2mdu 2183 1 The the DT cord-014597-66vd2mdu 2183 2 batch batch NN cord-014597-66vd2mdu 2183 3 process process NN cord-014597-66vd2mdu 2183 4 showed show VBD cord-014597-66vd2mdu 2183 5 an an DT cord-014597-66vd2mdu 2183 6 expected expect VBN cord-014597-66vd2mdu 2183 7 increase increase NN cord-014597-66vd2mdu 2183 8 in in IN cord-014597-66vd2mdu 2183 9 cell cell NN cord-014597-66vd2mdu 2183 10 density density NN cord-014597-66vd2mdu 2183 11 with with IN cord-014597-66vd2mdu 2183 12 low low JJ cord-014597-66vd2mdu 2183 13 variability variability NN cord-014597-66vd2mdu 2183 14 between between IN cord-014597-66vd2mdu 2183 15 biological biological JJ cord-014597-66vd2mdu 2183 16 replicates replicate NNS cord-014597-66vd2mdu 2183 17 ( ( -LRB- cord-014597-66vd2mdu 2183 18 Fig Fig NNP cord-014597-66vd2mdu 2183 19 . . . cord-014597-66vd2mdu 2183 20 1b 1b CD cord-014597-66vd2mdu 2183 21 ) ) -RRB- cord-014597-66vd2mdu 2183 22 . . . cord-014597-66vd2mdu 2184 1 The the DT cord-014597-66vd2mdu 2184 2 genomic genomic JJ cord-014597-66vd2mdu 2184 3 titer titer NN cord-014597-66vd2mdu 2184 4 increased increase VBD cord-014597-66vd2mdu 2184 5 according accord VBG cord-014597-66vd2mdu 2184 6 to to IN cord-014597-66vd2mdu 2184 7 the the DT cord-014597-66vd2mdu 2184 8 viable viable JJ cord-014597-66vd2mdu 2184 9 cell cell NN cord-014597-66vd2mdu 2184 10 density density NN cord-014597-66vd2mdu 2184 11 until until IN cord-014597-66vd2mdu 2184 12 day day NN cord-014597-66vd2mdu 2184 13 four four CD cord-014597-66vd2mdu 2184 14 where where WRB cord-014597-66vd2mdu 2184 15 a a DT cord-014597-66vd2mdu 2184 16 sudden sudden JJ cord-014597-66vd2mdu 2184 17 drop drop NN cord-014597-66vd2mdu 2184 18 started start VBD cord-014597-66vd2mdu 2184 19 . . . cord-014597-66vd2mdu 2185 1 This this DT cord-014597-66vd2mdu 2185 2 observation observation NN cord-014597-66vd2mdu 2185 3 was be VBD cord-014597-66vd2mdu 2185 4 made make VBN cord-014597-66vd2mdu 2185 5 for for IN cord-014597-66vd2mdu 2185 6 AAV AAV NNP cord-014597-66vd2mdu 2185 7 productions production NNS cord-014597-66vd2mdu 2185 8 in in IN cord-014597-66vd2mdu 2185 9 HEK HEK NNP cord-014597-66vd2mdu 2185 10 - - HYPH cord-014597-66vd2mdu 2185 11 TF TF NNP cord-014597-66vd2mdu 2185 12 , , , cord-014597-66vd2mdu 2185 13 HEK HEK NNP cord-014597-66vd2mdu 2185 14 - - HYPH cord-014597-66vd2mdu 2185 15 GM GM NNP cord-014597-66vd2mdu 2185 16 and and CC cord-014597-66vd2mdu 2185 17 Freestyle Freestyle NNP cord-014597-66vd2mdu 2185 18 F17 F17 NNP cord-014597-66vd2mdu 2185 19 medium medium NN cord-014597-66vd2mdu 2185 20 . . . cord-014597-66vd2mdu 2186 1 For for IN cord-014597-66vd2mdu 2186 2 optimal optimal JJ cord-014597-66vd2mdu 2186 3 yields yield NNS cord-014597-66vd2mdu 2186 4 , , , cord-014597-66vd2mdu 2186 5 we -PRON- PRP cord-014597-66vd2mdu 2186 6 assume assume VBP cord-014597-66vd2mdu 2186 7 that that IN cord-014597-66vd2mdu 2186 8 a a DT cord-014597-66vd2mdu 2186 9 slight slight JJ cord-014597-66vd2mdu 2186 10 decrease decrease NN cord-014597-66vd2mdu 2186 11 in in IN cord-014597-66vd2mdu 2186 12 viability viability NN cord-014597-66vd2mdu 2186 13 marks mark VBZ cord-014597-66vd2mdu 2186 14 the the DT cord-014597-66vd2mdu 2186 15 point point NN cord-014597-66vd2mdu 2186 16 in in IN cord-014597-66vd2mdu 2186 17 time time NN cord-014597-66vd2mdu 2186 18 for for IN cord-014597-66vd2mdu 2186 19 harvest harvest NN cord-014597-66vd2mdu 2186 20 . . . cord-014597-66vd2mdu 2187 1 From from IN cord-014597-66vd2mdu 2187 2 optimized optimize VBN cord-014597-66vd2mdu 2187 3 protocols protocol NNS cord-014597-66vd2mdu 2187 4 , , , cord-014597-66vd2mdu 2187 5 a a DT cord-014597-66vd2mdu 2187 6 batch batch NN cord-014597-66vd2mdu 2187 7 process process NN cord-014597-66vd2mdu 2187 8 in in IN cord-014597-66vd2mdu 2187 9 a a DT cord-014597-66vd2mdu 2187 10 2 2 CD cord-014597-66vd2mdu 2187 11 l l NN cord-014597-66vd2mdu 2187 12 bioreactor bioreactor NN cord-014597-66vd2mdu 2187 13 was be VBD cord-014597-66vd2mdu 2187 14 carried carry VBN cord-014597-66vd2mdu 2187 15 out out RP cord-014597-66vd2mdu 2187 16 . . . cord-014597-66vd2mdu 2188 1 Interestingly interestingly RB cord-014597-66vd2mdu 2188 2 the the DT cord-014597-66vd2mdu 2188 3 bioreactor bioreactor NN cord-014597-66vd2mdu 2188 4 cultivation cultivation NN cord-014597-66vd2mdu 2188 5 resulted result VBD cord-014597-66vd2mdu 2188 6 in in IN cord-014597-66vd2mdu 2188 7 lower low JJR cord-014597-66vd2mdu 2188 8 overall overall JJ cord-014597-66vd2mdu 2188 9 viable viable JJ cord-014597-66vd2mdu 2188 10 cell cell NN cord-014597-66vd2mdu 2188 11 densities density NNS cord-014597-66vd2mdu 2188 12 but but CC cord-014597-66vd2mdu 2188 13 in in IN cord-014597-66vd2mdu 2188 14 higher high JJR cord-014597-66vd2mdu 2188 15 genomic genomic JJ cord-014597-66vd2mdu 2188 16 copies copy NNS cord-014597-66vd2mdu 2188 17 per per IN cord-014597-66vd2mdu 2188 18 cell cell NN cord-014597-66vd2mdu 2188 19 compared compare VBN cord-014597-66vd2mdu 2188 20 to to IN cord-014597-66vd2mdu 2188 21 shaker shaker NN cord-014597-66vd2mdu 2188 22 flasks flask NNS cord-014597-66vd2mdu 2188 23 ( ( -LRB- cord-014597-66vd2mdu 2188 24 Fig Fig NNP cord-014597-66vd2mdu 2188 25 . . . cord-014597-66vd2mdu 2188 26 1c 1c CD cord-014597-66vd2mdu 2188 27 ) ) -RRB- cord-014597-66vd2mdu 2188 28 . . . cord-014597-66vd2mdu 2189 1 These these DT cord-014597-66vd2mdu 2189 2 results result NNS cord-014597-66vd2mdu 2189 3 are be VBP cord-014597-66vd2mdu 2189 4 comparable comparable JJ cord-014597-66vd2mdu 2189 5 to to IN cord-014597-66vd2mdu 2189 6 already already RB cord-014597-66vd2mdu 2189 7 published publish VBN cord-014597-66vd2mdu 2189 8 data datum NNS cord-014597-66vd2mdu 2189 9 for for IN cord-014597-66vd2mdu 2189 10 suspension suspension NN cord-014597-66vd2mdu 2189 11 cells cell NNS cord-014597-66vd2mdu 2189 12 [ [ -LRB- cord-014597-66vd2mdu 2189 13 2 2 CD cord-014597-66vd2mdu 2189 14 ] ] -RRB- cord-014597-66vd2mdu 2189 15 . . . cord-014597-66vd2mdu 2190 1 Subsequent subsequent JJ cord-014597-66vd2mdu 2190 2 optimization optimization NN cord-014597-66vd2mdu 2190 3 of of IN cord-014597-66vd2mdu 2190 4 the the DT cord-014597-66vd2mdu 2190 5 bioreactor bioreactor NN cord-014597-66vd2mdu 2190 6 protocol protocol NN cord-014597-66vd2mdu 2190 7 will will MD cord-014597-66vd2mdu 2190 8 lead lead VB cord-014597-66vd2mdu 2190 9 to to IN cord-014597-66vd2mdu 2190 10 further further JJ cord-014597-66vd2mdu 2190 11 increase increase VB cord-014597-66vd2mdu 2190 12 in in IN cord-014597-66vd2mdu 2190 13 rAAV raav JJ cord-014597-66vd2mdu 2190 14 yield yield NN cord-014597-66vd2mdu 2190 15 . . . cord-014597-66vd2mdu 2191 1 Genethon Genethon NNP cord-014597-66vd2mdu 2191 2 and and CC cord-014597-66vd2mdu 2191 3 Pall Pall NNP cord-014597-66vd2mdu 2191 4 have have VBP cord-014597-66vd2mdu 2191 5 collaborated collaborate VBN cord-014597-66vd2mdu 2191 6 to to TO cord-014597-66vd2mdu 2191 7 assess assess VB cord-014597-66vd2mdu 2191 8 Pall Pall NNP cord-014597-66vd2mdu 2191 9 's 's POS cord-014597-66vd2mdu 2191 10 single single JJ cord-014597-66vd2mdu 2191 11 - - HYPH cord-014597-66vd2mdu 2191 12 use use NN cord-014597-66vd2mdu 2191 13 iCELLis iCELLis NNP cord-014597-66vd2mdu 2191 14 fixed fix VBN cord-014597-66vd2mdu 2191 15 - - HYPH cord-014597-66vd2mdu 2191 16 bed bed NN cord-014597-66vd2mdu 2191 17 bioreactor bioreactor NN cord-014597-66vd2mdu 2191 18 for for IN cord-014597-66vd2mdu 2191 19 viral viral JJ cord-014597-66vd2mdu 2191 20 vector vector NN cord-014597-66vd2mdu 2191 21 production production NN cord-014597-66vd2mdu 2191 22 . . . cord-014597-66vd2mdu 2192 1 Clinical clinical JJ cord-014597-66vd2mdu 2192 2 use use NN cord-014597-66vd2mdu 2192 3 of of IN cord-014597-66vd2mdu 2192 4 gene gene NN cord-014597-66vd2mdu 2192 5 therapies therapy NNS cord-014597-66vd2mdu 2192 6 to to TO cord-014597-66vd2mdu 2192 7 treat treat VB cord-014597-66vd2mdu 2192 8 formerly formerly RB cord-014597-66vd2mdu 2192 9 incurable incurable JJ cord-014597-66vd2mdu 2192 10 genetic genetic JJ cord-014597-66vd2mdu 2192 11 diseases disease NNS cord-014597-66vd2mdu 2192 12 is be VBZ cord-014597-66vd2mdu 2192 13 advancing advance VBG cord-014597-66vd2mdu 2192 14 rapidly rapidly RB cord-014597-66vd2mdu 2192 15 . . . cord-014597-66vd2mdu 2193 1 Viral viral JJ cord-014597-66vd2mdu 2193 2 vectors vector NNS cord-014597-66vd2mdu 2193 3 are be VBP cord-014597-66vd2mdu 2193 4 an an DT cord-014597-66vd2mdu 2193 5 important important JJ cord-014597-66vd2mdu 2193 6 tool tool NN cord-014597-66vd2mdu 2193 7 for for IN cord-014597-66vd2mdu 2193 8 introducing introduce VBG cord-014597-66vd2mdu 2193 9 genes gene NNS cord-014597-66vd2mdu 2193 10 into into IN cord-014597-66vd2mdu 2193 11 target target NN cord-014597-66vd2mdu 2193 12 cells cell NNS cord-014597-66vd2mdu 2193 13 . . . cord-014597-66vd2mdu 2194 1 Many many JJ cord-014597-66vd2mdu 2194 2 gene gene NN cord-014597-66vd2mdu 2194 3 therapies therapy NNS cord-014597-66vd2mdu 2194 4 have have VBP cord-014597-66vd2mdu 2194 5 been be VBN cord-014597-66vd2mdu 2194 6 developed develop VBN cord-014597-66vd2mdu 2194 7 using use VBG cord-014597-66vd2mdu 2194 8 adherent adherent JJ cord-014597-66vd2mdu 2194 9 cells cell NNS cord-014597-66vd2mdu 2194 10 in in IN cord-014597-66vd2mdu 2194 11 2-dimensional 2-dimensional JJ cord-014597-66vd2mdu 2194 12 flatware flatware NN cord-014597-66vd2mdu 2194 13 or or CC cord-014597-66vd2mdu 2194 14 roller roller NN cord-014597-66vd2mdu 2194 15 bottles bottle NNS cord-014597-66vd2mdu 2194 16 but but CC cord-014597-66vd2mdu 2194 17 using use VBG cord-014597-66vd2mdu 2194 18 these these DT cord-014597-66vd2mdu 2194 19 technologies technology NNS cord-014597-66vd2mdu 2194 20 to to TO cord-014597-66vd2mdu 2194 21 reach reach VB cord-014597-66vd2mdu 2194 22 commercial commercial JJ cord-014597-66vd2mdu 2194 23 - - HYPH cord-014597-66vd2mdu 2194 24 scale scale NN cord-014597-66vd2mdu 2194 25 production production NN cord-014597-66vd2mdu 2194 26 represents represent VBZ cord-014597-66vd2mdu 2194 27 a a DT cord-014597-66vd2mdu 2194 28 significant significant JJ cord-014597-66vd2mdu 2194 29 challenge challenge NN cord-014597-66vd2mdu 2194 30 . . . cord-014597-66vd2mdu 2195 1 The the DT cord-014597-66vd2mdu 2195 2 iCELLis iCELLis NNP cord-014597-66vd2mdu 2195 3 bioreactor bioreactor NN cord-014597-66vd2mdu 2195 4 enables enable VBZ cord-014597-66vd2mdu 2195 5 large large JJ cord-014597-66vd2mdu 2195 6 - - HYPH cord-014597-66vd2mdu 2195 7 scale scale NN cord-014597-66vd2mdu 2195 8 viral viral JJ cord-014597-66vd2mdu 2195 9 vector vector NN cord-014597-66vd2mdu 2195 10 production production NN cord-014597-66vd2mdu 2195 11 by by IN cord-014597-66vd2mdu 2195 12 providing provide VBG cord-014597-66vd2mdu 2195 13 a a DT cord-014597-66vd2mdu 2195 14 3-dimensional 3-dimensional CD cord-014597-66vd2mdu 2195 15 matrix matrix NN cord-014597-66vd2mdu 2195 16 for for IN cord-014597-66vd2mdu 2195 17 cell cell NN cord-014597-66vd2mdu 2195 18 growth growth NN cord-014597-66vd2mdu 2195 19 in in IN cord-014597-66vd2mdu 2195 20 a a DT cord-014597-66vd2mdu 2195 21 compact compact JJ cord-014597-66vd2mdu 2195 22 configuration configuration NN cord-014597-66vd2mdu 2195 23 ( ( -LRB- cord-014597-66vd2mdu 2195 24 Fig Fig NNP cord-014597-66vd2mdu 2195 25 . . . cord-014597-66vd2mdu 2195 26 1 1 CD cord-014597-66vd2mdu 2195 27 ) ) -RRB- cord-014597-66vd2mdu 2195 28 . . . cord-014597-66vd2mdu 2196 1 Up up IN cord-014597-66vd2mdu 2196 2 to to TO cord-014597-66vd2mdu 2196 3 500 500 CD cord-014597-66vd2mdu 2196 4 m m CD cord-014597-66vd2mdu 2196 5 2 2 CD cord-014597-66vd2mdu 2196 6 of of IN cord-014597-66vd2mdu 2196 7 surface surface NN cord-014597-66vd2mdu 2196 8 area area NN cord-014597-66vd2mdu 2196 9 is be VBZ cord-014597-66vd2mdu 2196 10 available available JJ cord-014597-66vd2mdu 2196 11 in in IN cord-014597-66vd2mdu 2196 12 a a DT cord-014597-66vd2mdu 2196 13 compact compact JJ cord-014597-66vd2mdu 2196 14 bioreactor bioreactor NN cord-014597-66vd2mdu 2196 15 measuring measure VBG cord-014597-66vd2mdu 2196 16 88 88 CD cord-014597-66vd2mdu 2196 17 mm mm NNS cord-014597-66vd2mdu 2196 18 in in IN cord-014597-66vd2mdu 2196 19 diameter diameter NN cord-014597-66vd2mdu 2196 20 in in IN cord-014597-66vd2mdu 2196 21 a a DT cord-014597-66vd2mdu 2196 22 total total JJ cord-014597-66vd2mdu 2196 23 volume volume NN cord-014597-66vd2mdu 2196 24 of of IN cord-014597-66vd2mdu 2196 25 75 75 CD cord-014597-66vd2mdu 2196 26 L l NN cord-014597-66vd2mdu 2196 27 with with IN cord-014597-66vd2mdu 2196 28 pH ph NN cord-014597-66vd2mdu 2196 29 , , , cord-014597-66vd2mdu 2196 30 DO do VB cord-014597-66vd2mdu 2196 31 and and CC cord-014597-66vd2mdu 2196 32 temperature temperature NN cord-014597-66vd2mdu 2196 33 control control NN cord-014597-66vd2mdu 2196 34 . . . cord-014597-66vd2mdu 2197 1 A a DT cord-014597-66vd2mdu 2197 2 key key JJ cord-014597-66vd2mdu 2197 3 feature feature NN cord-014597-66vd2mdu 2197 4 of of IN cord-014597-66vd2mdu 2197 5 the the DT cord-014597-66vd2mdu 2197 6 iCELLis iCELLis NNP cord-014597-66vd2mdu 2197 7 bioreactor bioreactor NN cord-014597-66vd2mdu 2197 8 is be VBZ cord-014597-66vd2mdu 2197 9 that that IN cord-014597-66vd2mdu 2197 10 it -PRON- PRP cord-014597-66vd2mdu 2197 11 scales scale VBZ cord-014597-66vd2mdu 2197 12 by by IN cord-014597-66vd2mdu 2197 13 increasing increase VBG cord-014597-66vd2mdu 2197 14 the the DT cord-014597-66vd2mdu 2197 15 diameter diameter NN cord-014597-66vd2mdu 2197 16 of of IN cord-014597-66vd2mdu 2197 17 the the DT cord-014597-66vd2mdu 2197 18 fixed fix VBN cord-014597-66vd2mdu 2197 19 - - HYPH cord-014597-66vd2mdu 2197 20 bed bed NN cord-014597-66vd2mdu 2197 21 while while IN cord-014597-66vd2mdu 2197 22 keeping keep VBG cord-014597-66vd2mdu 2197 23 the the DT cord-014597-66vd2mdu 2197 24 height height NN cord-014597-66vd2mdu 2197 25 constant constant JJ cord-014597-66vd2mdu 2197 26 with with IN cord-014597-66vd2mdu 2197 27 no no DT cord-014597-66vd2mdu 2197 28 change change NN cord-014597-66vd2mdu 2197 29 in in IN cord-014597-66vd2mdu 2197 30 aspect aspect NN cord-014597-66vd2mdu 2197 31 ratios ratio NNS cord-014597-66vd2mdu 2197 32 . . . cord-014597-66vd2mdu 2198 1 The the DT cord-014597-66vd2mdu 2198 2 height height NN cord-014597-66vd2mdu 2198 3 of of IN cord-014597-66vd2mdu 2198 4 the the DT cord-014597-66vd2mdu 2198 5 fixed fix VBN cord-014597-66vd2mdu 2198 6 - - HYPH cord-014597-66vd2mdu 2198 7 bed bed NN cord-014597-66vd2mdu 2198 8 can can MD cord-014597-66vd2mdu 2198 9 be be VB cord-014597-66vd2mdu 2198 10 varied varied JJ cord-014597-66vd2mdu 2198 11 ( ( -LRB- cord-014597-66vd2mdu 2198 12 2 2 CD cord-014597-66vd2mdu 2198 13 , , , cord-014597-66vd2mdu 2198 14 4 4 CD cord-014597-66vd2mdu 2198 15 and and CC cord-014597-66vd2mdu 2198 16 10 10 CD cord-014597-66vd2mdu 2198 17 cm cm NNS cord-014597-66vd2mdu 2198 18 ) ) -RRB- cord-014597-66vd2mdu 2198 19 as as RB cord-014597-66vd2mdu 2198 20 well well RB cord-014597-66vd2mdu 2198 21 as as IN cord-014597-66vd2mdu 2198 22 density density NN cord-014597-66vd2mdu 2198 23 of of IN cord-014597-66vd2mdu 2198 24 carrier carrier NN cord-014597-66vd2mdu 2198 25 packing packing NN cord-014597-66vd2mdu 2198 26 ( ( -LRB- cord-014597-66vd2mdu 2198 27 96 96 CD cord-014597-66vd2mdu 2198 28 gm gm NNP cord-014597-66vd2mdu 2198 29 / / SYM cord-014597-66vd2mdu 2198 30 L L NNP cord-014597-66vd2mdu 2198 31 or or CC cord-014597-66vd2mdu 2198 32 144 144 CD cord-014597-66vd2mdu 2198 33 gm gm NNP cord-014597-66vd2mdu 2198 34 / / SYM cord-014597-66vd2mdu 2198 35 L L NNP cord-014597-66vd2mdu 2198 36 ) ) -RRB- cord-014597-66vd2mdu 2198 37 . . . cord-014597-66vd2mdu 2199 1 The the DT cord-014597-66vd2mdu 2199 2 iCELLis iCELLis NNP cord-014597-66vd2mdu 2199 3 system system NN cord-014597-66vd2mdu 2199 4 comes come VBZ cord-014597-66vd2mdu 2199 5 in in IN cord-014597-66vd2mdu 2199 6 two two CD cord-014597-66vd2mdu 2199 7 formats format NNS cord-014597-66vd2mdu 2199 8 , , , cord-014597-66vd2mdu 2199 9 the the DT cord-014597-66vd2mdu 2199 10 iCELLis iCELLis NNP cord-014597-66vd2mdu 2199 11 Nano Nano NNP cord-014597-66vd2mdu 2199 12 bioreactor bioreactor NN cord-014597-66vd2mdu 2199 13 ( ( -LRB- cord-014597-66vd2mdu 2199 14 0.53 0.53 CD cord-014597-66vd2mdu 2199 15 - - SYM cord-014597-66vd2mdu 2199 16 4.0 4.0 CD cord-014597-66vd2mdu 2199 17 m m CD cord-014597-66vd2mdu 2199 18 2 2 CD cord-014597-66vd2mdu 2199 19 ) ) -RRB- cord-014597-66vd2mdu 2199 20 and and CC cord-014597-66vd2mdu 2199 21 the the DT cord-014597-66vd2mdu 2199 22 iCELLis iCELLis NNP cord-014597-66vd2mdu 2199 23 500 500 CD cord-014597-66vd2mdu 2199 24 bioreactor bioreactor NN cord-014597-66vd2mdu 2199 25 ( ( -LRB- cord-014597-66vd2mdu 2199 26 66 66 CD cord-014597-66vd2mdu 2199 27 - - SYM cord-014597-66vd2mdu 2199 28 500 500 CD cord-014597-66vd2mdu 2199 29 m m CD cord-014597-66vd2mdu 2199 30 2 2 CD cord-014597-66vd2mdu 2199 31 ) ) -RRB- cord-014597-66vd2mdu 2199 32 . . . cord-014597-66vd2mdu 2200 1 Processes process NNS cord-014597-66vd2mdu 2200 2 developed develop VBN cord-014597-66vd2mdu 2200 3 in in IN cord-014597-66vd2mdu 2200 4 the the DT cord-014597-66vd2mdu 2200 5 bench bench NN cord-014597-66vd2mdu 2200 6 top top NN cord-014597-66vd2mdu 2200 7 iCELLis iCELLis NNP cord-014597-66vd2mdu 2200 8 Nano Nano NNP cord-014597-66vd2mdu 2200 9 bioreactor bioreactor NN cord-014597-66vd2mdu 2200 10 can can MD cord-014597-66vd2mdu 2200 11 be be VB cord-014597-66vd2mdu 2200 12 directly directly RB cord-014597-66vd2mdu 2200 13 transferred transfer VBN cord-014597-66vd2mdu 2200 14 to to IN cord-014597-66vd2mdu 2200 15 the the DT cord-014597-66vd2mdu 2200 16 corresponding corresponding JJ cord-014597-66vd2mdu 2200 17 iCELLis iCELLis NNP cord-014597-66vd2mdu 2200 18 500 500 CD cord-014597-66vd2mdu 2200 19 system system NN cord-014597-66vd2mdu 2200 20 . . . cord-014597-66vd2mdu 2201 1 The the DT cord-014597-66vd2mdu 2201 2 iCELLis iCELLis NNP cord-014597-66vd2mdu 2201 3 Nano Nano NNP cord-014597-66vd2mdu 2201 4 bioreactor bioreactor NN cord-014597-66vd2mdu 2201 5 enables enable VBZ cord-014597-66vd2mdu 2201 6 an an DT cord-014597-66vd2mdu 2201 7 efficient efficient JJ cord-014597-66vd2mdu 2201 8 platform platform NN cord-014597-66vd2mdu 2201 9 for for IN cord-014597-66vd2mdu 2201 10 process process NN cord-014597-66vd2mdu 2201 11 optimization optimization NN cord-014597-66vd2mdu 2201 12 . . . cord-014597-66vd2mdu 2201 13 _SP cord-014597-66vd2mdu 2202 1 The the DT cord-014597-66vd2mdu 2202 2 Genethon Genethon NNP cord-014597-66vd2mdu 2203 1 rAAV-8 raav-8 LS cord-014597-66vd2mdu 2203 2 process process NN cord-014597-66vd2mdu 2203 3 was be VBD cord-014597-66vd2mdu 2203 4 transferred transfer VBN cord-014597-66vd2mdu 2203 5 to to IN cord-014597-66vd2mdu 2203 6 an an DT cord-014597-66vd2mdu 2203 7 iCELLis iCELLis NNP cord-014597-66vd2mdu 2203 8 Nano Nano NNP cord-014597-66vd2mdu 2203 9 bioreactor bioreactor NN cord-014597-66vd2mdu 2203 10 0.8 0.8 CD cord-014597-66vd2mdu 2203 11 m m CD cord-014597-66vd2mdu 2203 12 2 2 CD cord-014597-66vd2mdu 2203 13 ( ( -LRB- cord-014597-66vd2mdu 2203 14 2 2 CD cord-014597-66vd2mdu 2203 15 cm cm NN cord-014597-66vd2mdu 2203 16 bed bed NN cord-014597-66vd2mdu 2203 17 height height NN cord-014597-66vd2mdu 2203 18 , , , cord-014597-66vd2mdu 2203 19 144 144 CD cord-014597-66vd2mdu 2203 20 gm gm NNP cord-014597-66vd2mdu 2203 21 / / SYM cord-014597-66vd2mdu 2203 22 L l NN cord-014597-66vd2mdu 2203 23 density density NN cord-014597-66vd2mdu 2203 24 ) ) -RRB- cord-014597-66vd2mdu 2203 25 bioreactor bioreactor NN cord-014597-66vd2mdu 2203 26 using use VBG cord-014597-66vd2mdu 2203 27 FreeStyle FreeStyle NNP cord-014597-66vd2mdu 2203 28 media medium NNS cord-014597-66vd2mdu 2203 29 . . . cord-014597-66vd2mdu 2204 1 The the DT cord-014597-66vd2mdu 2204 2 initial initial JJ cord-014597-66vd2mdu 2204 3 iCELLis iCELLis NNP cord-014597-66vd2mdu 2204 4 Nano Nano NNP cord-014597-66vd2mdu 2204 5 process process NN cord-014597-66vd2mdu 2204 6 was be VBD cord-014597-66vd2mdu 2204 7 established establish VBN cord-014597-66vd2mdu 2204 8 as as IN cord-014597-66vd2mdu 2204 9 ( ( -LRB- cord-014597-66vd2mdu 2204 10 1 1 CD cord-014597-66vd2mdu 2204 11 ) ) -RRB- cord-014597-66vd2mdu 2204 12 seed seed NN cord-014597-66vd2mdu 2204 13 on on IN cord-014597-66vd2mdu 2204 14 Day day NN cord-014597-66vd2mdu 2204 15 1 1 CD cord-014597-66vd2mdu 2204 16 , , , cord-014597-66vd2mdu 2204 17 ( ( -LRB- cord-014597-66vd2mdu 2204 18 2 2 LS cord-014597-66vd2mdu 2204 19 ) ) -RRB- cord-014597-66vd2mdu 2204 20 transfect transfect VB cord-014597-66vd2mdu 2204 21 at at IN cord-014597-66vd2mdu 2204 22 Day day NN cord-014597-66vd2mdu 2204 23 5 5 CD cord-014597-66vd2mdu 2204 24 , , , cord-014597-66vd2mdu 2204 25 ( ( -LRB- cord-014597-66vd2mdu 2204 26 3 3 LS cord-014597-66vd2mdu 2204 27 ) ) -RRB- cord-014597-66vd2mdu 2204 28 harvest harvest NN cord-014597-66vd2mdu 2204 29 at at IN cord-014597-66vd2mdu 2204 30 Day day NN cord-014597-66vd2mdu 2204 31 8 8 CD cord-014597-66vd2mdu 2204 32 and and CC cord-014597-66vd2mdu 2204 33 yielded yield VBD cord-014597-66vd2mdu 2204 34 < < NNP cord-014597-66vd2mdu 2204 35 1x 1x CD cord-014597-66vd2mdu 2204 36 10 10 CD cord-014597-66vd2mdu 2204 37 9 9 CD cord-014597-66vd2mdu 2204 38 vp vp NNP cord-014597-66vd2mdu 2204 39 / / SYM cord-014597-66vd2mdu 2204 40 cm cm NNP cord-014597-66vd2mdu 2204 41 2 2 CD cord-014597-66vd2mdu 2204 42 ( ( -LRB- cord-014597-66vd2mdu 2204 43 n=3 n=3 NN cord-014597-66vd2mdu 2204 44 ) ) -RRB- cord-014597-66vd2mdu 2204 45 . . . cord-014597-66vd2mdu 2205 1 Media Media NNP cord-014597-66vd2mdu 2205 2 exchange exchange NN cord-014597-66vd2mdu 2205 3 , , , cord-014597-66vd2mdu 2205 4 cell cell NN cord-014597-66vd2mdu 2205 5 density density NN cord-014597-66vd2mdu 2205 6 at at IN cord-014597-66vd2mdu 2205 7 transfection transfection NN cord-014597-66vd2mdu 2205 8 , , , cord-014597-66vd2mdu 2205 9 pDNA pdna JJ cord-014597-66vd2mdu 2205 10 / / SYM cord-014597-66vd2mdu 2205 11 cell cell NN cord-014597-66vd2mdu 2205 12 ratio ratio NN cord-014597-66vd2mdu 2205 13 , , , cord-014597-66vd2mdu 2205 14 and and CC cord-014597-66vd2mdu 2205 15 lysis lysis NN cord-014597-66vd2mdu 2205 16 method method NN cord-014597-66vd2mdu 2205 17 were be VBD cord-014597-66vd2mdu 2205 18 then then RB cord-014597-66vd2mdu 2205 19 changed change VBN cord-014597-66vd2mdu 2205 20 to to TO cord-014597-66vd2mdu 2205 21 determine determine VB cord-014597-66vd2mdu 2205 22 the the DT cord-014597-66vd2mdu 2205 23 effect effect NN cord-014597-66vd2mdu 2205 24 on on IN cord-014597-66vd2mdu 2205 25 productivity productivity NN cord-014597-66vd2mdu 2205 26 . . . cord-014597-66vd2mdu 2206 1 The the DT cord-014597-66vd2mdu 2206 2 modified modified JJ cord-014597-66vd2mdu 2206 3 process process NN cord-014597-66vd2mdu 2206 4 was be VBD cord-014597-66vd2mdu 2206 5 then then RB cord-014597-66vd2mdu 2206 6 scaled scale VBN cord-014597-66vd2mdu 2206 7 from from IN cord-014597-66vd2mdu 2206 8 0.8 0.8 CD cord-014597-66vd2mdu 2206 9 m m CD cord-014597-66vd2mdu 2206 10 2 2 CD cord-014597-66vd2mdu 2206 11 to to IN cord-014597-66vd2mdu 2206 12 4.0 4.0 CD cord-014597-66vd2mdu 2206 13 m m CD cord-014597-66vd2mdu 2206 14 2 2 CD cord-014597-66vd2mdu 2206 15 ( ( -LRB- cord-014597-66vd2mdu 2206 16 10 10 CD cord-014597-66vd2mdu 2206 17 cm cm NN cord-014597-66vd2mdu 2206 18 bed bed NN cord-014597-66vd2mdu 2206 19 height height NN cord-014597-66vd2mdu 2206 20 , , , cord-014597-66vd2mdu 2206 21 144 144 CD cord-014597-66vd2mdu 2206 22 gm gm NNP cord-014597-66vd2mdu 2206 23 / / SYM cord-014597-66vd2mdu 2206 24 L l NN cord-014597-66vd2mdu 2206 25 density density NN cord-014597-66vd2mdu 2206 26 ) ) -RRB- cord-014597-66vd2mdu 2207 1 iCELLis iCELLis NNP cord-014597-66vd2mdu 2207 2 Nano Nano NNP cord-014597-66vd2mdu 2207 3 bioreactor bioreactor NN cord-014597-66vd2mdu 2207 4 . . . cord-014597-66vd2mdu 2208 1 -Media -Media NNP cord-014597-66vd2mdu 2209 1 : : : cord-014597-66vd2mdu 2209 2 A a DT cord-014597-66vd2mdu 2209 3 media media NN cord-014597-66vd2mdu 2209 4 exchange exchange NN cord-014597-66vd2mdu 2209 5 at at IN cord-014597-66vd2mdu 2209 6 5 5 CD cord-014597-66vd2mdu 2209 7 hours hour NNS cord-014597-66vd2mdu 2209 8 post post NN cord-014597-66vd2mdu 2209 9 transfection transfection NN cord-014597-66vd2mdu 2209 10 with with IN cord-014597-66vd2mdu 2209 11 DMEM DMEM NNP cord-014597-66vd2mdu 2209 12 substituted substitute VBN cord-014597-66vd2mdu 2209 13 for for IN cord-014597-66vd2mdu 2209 14 FreeStyle FreeStyle NNP cord-014597-66vd2mdu 2209 15 medium medium NN cord-014597-66vd2mdu 2209 16 resulted result VBD cord-014597-66vd2mdu 2209 17 in in IN cord-014597-66vd2mdu 2209 18 an an DT cord-014597-66vd2mdu 2209 19 8x 8x CD cord-014597-66vd2mdu 2209 20 increase increase NN cord-014597-66vd2mdu 2209 21 in in IN cord-014597-66vd2mdu 2209 22 specific specific JJ cord-014597-66vd2mdu 2209 23 productivity productivity NN cord-014597-66vd2mdu 2209 24 . . . cord-014597-66vd2mdu 2210 1 1 1 LS cord-014597-66vd2mdu 2211 1 ( ( -LRB- cord-014597-66vd2mdu 2211 2 abstract abstract NNP cord-014597-66vd2mdu 2211 3 P-349 P-349 NNP cord-014597-66vd2mdu 2211 4 ) ) -RRB- cord-014597-66vd2mdu 2211 5 . . . cord-014597-66vd2mdu 2212 1 a a DT cord-014597-66vd2mdu 2212 2 Schematic schematic JJ cord-014597-66vd2mdu 2212 3 overview overview NN cord-014597-66vd2mdu 2212 4 of of IN cord-014597-66vd2mdu 2212 5 rAAV raav NN cord-014597-66vd2mdu 2212 6 production production NN cord-014597-66vd2mdu 2212 7 in in IN cord-014597-66vd2mdu 2212 8 HEK293 HEK293 NNP cord-014597-66vd2mdu 2212 9 cells cell NNS cord-014597-66vd2mdu 2212 10 with with IN cord-014597-66vd2mdu 2212 11 triple triple JJ cord-014597-66vd2mdu 2212 12 - - HYPH cord-014597-66vd2mdu 2212 13 transfection transfection NN cord-014597-66vd2mdu 2212 14 system system NN cord-014597-66vd2mdu 2212 15 . . . cord-014597-66vd2mdu 2213 1 b b LS cord-014597-66vd2mdu 2213 2 Viable viable JJ cord-014597-66vd2mdu 2213 3 cell cell NN cord-014597-66vd2mdu 2213 4 densities density NNS cord-014597-66vd2mdu 2213 5 ( ( -LRB- cord-014597-66vd2mdu 2213 6 VCD VCD NNP cord-014597-66vd2mdu 2213 7 ) ) -RRB- cord-014597-66vd2mdu 2213 8 , , , cord-014597-66vd2mdu 2213 9 viabilities viability NNS cord-014597-66vd2mdu 2213 10 and and CC cord-014597-66vd2mdu 2213 11 genomic genomic JJ cord-014597-66vd2mdu 2213 12 copies copy NNS cord-014597-66vd2mdu 2213 13 per per IN cord-014597-66vd2mdu 2213 14 ml ml NN cord-014597-66vd2mdu 2213 15 ( ( -LRB- cord-014597-66vd2mdu 2213 16 GC GC NNP cord-014597-66vd2mdu 2213 17 ) ) -RRB- cord-014597-66vd2mdu 2213 18 of of IN cord-014597-66vd2mdu 2213 19 a a DT cord-014597-66vd2mdu 2213 20 rAAV raav JJ cord-014597-66vd2mdu 2213 21 production production NN cord-014597-66vd2mdu 2213 22 with with IN cord-014597-66vd2mdu 2213 23 293-F 293-f CD cord-014597-66vd2mdu 2213 24 batch batch NN cord-014597-66vd2mdu 2213 25 cultivations cultivation NNS cord-014597-66vd2mdu 2213 26 in in IN cord-014597-66vd2mdu 2213 27 shaker shaker NN cord-014597-66vd2mdu 2213 28 flasks flask NNS cord-014597-66vd2mdu 2213 29 . . . cord-014597-66vd2mdu 2214 1 Genomic genomic JJ cord-014597-66vd2mdu 2214 2 copies copy NNS cord-014597-66vd2mdu 2214 3 per per IN cord-014597-66vd2mdu 2214 4 ml ml NNS cord-014597-66vd2mdu 2214 5 refer refer NN cord-014597-66vd2mdu 2214 6 to to IN cord-014597-66vd2mdu 2214 7 the the DT cord-014597-66vd2mdu 2214 8 titer titer NN cord-014597-66vd2mdu 2214 9 determined determine VBN cord-014597-66vd2mdu 2214 10 in in IN cord-014597-66vd2mdu 2214 11 1 1 CD cord-014597-66vd2mdu 2214 12 ml ml NN cord-014597-66vd2mdu 2214 13 culture culture NN cord-014597-66vd2mdu 2214 14 volume volume NN cord-014597-66vd2mdu 2214 15 . . . cord-014597-66vd2mdu 2215 1 Error error NN cord-014597-66vd2mdu 2215 2 bars bar NNS cord-014597-66vd2mdu 2215 3 represent represent VBP cord-014597-66vd2mdu 2215 4 biological biological JJ cord-014597-66vd2mdu 2215 5 and and CC cord-014597-66vd2mdu 2215 6 technical technical JJ cord-014597-66vd2mdu 2215 7 duplicate duplicate JJ cord-014597-66vd2mdu 2215 8 measurements measurement NNS cord-014597-66vd2mdu 2215 9 of of IN cord-014597-66vd2mdu 2215 10 samples sample NNS cord-014597-66vd2mdu 2215 11 . . . cord-014597-66vd2mdu 2216 1 c c LS cord-014597-66vd2mdu 2216 2 Viable viable JJ cord-014597-66vd2mdu 2216 3 cell cell NN cord-014597-66vd2mdu 2216 4 densities density NNS cord-014597-66vd2mdu 2216 5 and and CC cord-014597-66vd2mdu 2216 6 genomic genomic JJ cord-014597-66vd2mdu 2216 7 copies copy NNS cord-014597-66vd2mdu 2216 8 per per IN cord-014597-66vd2mdu 2216 9 cell cell NN cord-014597-66vd2mdu 2216 10 of of IN cord-014597-66vd2mdu 2216 11 a a DT cord-014597-66vd2mdu 2216 12 rAAV raav NN cord-014597-66vd2mdu 2216 13 production production NN cord-014597-66vd2mdu 2216 14 with with IN cord-014597-66vd2mdu 2216 15 293-F 293-f CD cord-014597-66vd2mdu 2216 16 batch batch NN cord-014597-66vd2mdu 2216 17 cultivation cultivation NN cord-014597-66vd2mdu 2216 18 in in IN cord-014597-66vd2mdu 2216 19 a a DT cord-014597-66vd2mdu 2216 20 2 2 CD cord-014597-66vd2mdu 2216 21 l l NN cord-014597-66vd2mdu 2216 22 bioreactor bioreactor NN cord-014597-66vd2mdu 2216 23 . . . cord-014597-66vd2mdu 2217 1 For for IN cord-014597-66vd2mdu 2217 2 reasons reason NNS cord-014597-66vd2mdu 2217 3 of of IN cord-014597-66vd2mdu 2217 4 comparability comparability NN cord-014597-66vd2mdu 2217 5 between between IN cord-014597-66vd2mdu 2217 6 shaker shaker NN cord-014597-66vd2mdu 2217 7 and and CC cord-014597-66vd2mdu 2217 8 bioreactor bioreactor NN cord-014597-66vd2mdu 2217 9 data datum NNS cord-014597-66vd2mdu 2217 10 genomic genomic JJ cord-014597-66vd2mdu 2217 11 copies copy NNS cord-014597-66vd2mdu 2217 12 are be VBP cord-014597-66vd2mdu 2217 13 given give VBN cord-014597-66vd2mdu 2217 14 per per IN cord-014597-66vd2mdu 2217 15 cell cell NN cord-014597-66vd2mdu 2217 16 . . . cord-014597-66vd2mdu 2218 1 Error error NN cord-014597-66vd2mdu 2218 2 bars bar NNS cord-014597-66vd2mdu 2218 3 represent represent VBP cord-014597-66vd2mdu 2218 4 technical technical JJ cord-014597-66vd2mdu 2218 5 duplicate duplicate JJ cord-014597-66vd2mdu 2218 6 measurements measurement NNS cord-014597-66vd2mdu 2218 7 of of IN cord-014597-66vd2mdu 2218 8 samples sample NNS cord-014597-66vd2mdu 2218 9 -Cell -Cell JJR cord-014597-66vd2mdu 2218 10 density density NN cord-014597-66vd2mdu 2218 11 at at IN cord-014597-66vd2mdu 2218 12 transfection transfection NN cord-014597-66vd2mdu 2218 13 : : : cord-014597-66vd2mdu 2219 1 Cells cell NNS cord-014597-66vd2mdu 2219 2 were be VBD cord-014597-66vd2mdu 2219 3 seeded seed VBN cord-014597-66vd2mdu 2219 4 at at IN cord-014597-66vd2mdu 2219 5 6,000 6,000 CD cord-014597-66vd2mdu 2219 6 cells cell NNS cord-014597-66vd2mdu 2219 7 / / SYM cord-014597-66vd2mdu 2219 8 cm cm NN cord-014597-66vd2mdu 2219 9 2 2 CD cord-014597-66vd2mdu 2219 10 and and CC cord-014597-66vd2mdu 2219 11 reached reach VBD cord-014597-66vd2mdu 2219 12 200,000 200,000 CD cord-014597-66vd2mdu 2219 13 cells cell NNS cord-014597-66vd2mdu 2219 14 / / SYM cord-014597-66vd2mdu 2219 15 cm cm NN cord-014597-66vd2mdu 2219 16 2 2 CD cord-014597-66vd2mdu 2219 17 at at IN cord-014597-66vd2mdu 2219 18 Day day NN cord-014597-66vd2mdu 2219 19 5 5 CD cord-014597-66vd2mdu 2219 20 which which WDT cord-014597-66vd2mdu 2219 21 was be VBD cord-014597-66vd2mdu 2219 22 determined determine VBN cord-014597-66vd2mdu 2219 23 to to TO cord-014597-66vd2mdu 2219 24 be be VB cord-014597-66vd2mdu 2219 25 the the DT cord-014597-66vd2mdu 2219 26 optimal optimal JJ cord-014597-66vd2mdu 2219 27 cell cell NN cord-014597-66vd2mdu 2219 28 density density NN cord-014597-66vd2mdu 2219 29 for for IN cord-014597-66vd2mdu 2219 30 transfection transfection NN cord-014597-66vd2mdu 2219 31 . . . cord-014597-66vd2mdu 2220 1 -pDNA -pDNA . cord-014597-66vd2mdu 2221 1 /cell /cell NNP cord-014597-66vd2mdu 2221 2 ratio ratio NN cord-014597-66vd2mdu 2221 3 : : : cord-014597-66vd2mdu 2222 1 Reducing reduce VBG cord-014597-66vd2mdu 2222 2 pDNA pdna RB cord-014597-66vd2mdu 2222 3 by by IN cord-014597-66vd2mdu 2222 4 50 50 CD cord-014597-66vd2mdu 2222 5 % % NN cord-014597-66vd2mdu 2222 6 had have VBD cord-014597-66vd2mdu 2222 7 no no DT cord-014597-66vd2mdu 2222 8 significant significant JJ cord-014597-66vd2mdu 2222 9 effect effect NN cord-014597-66vd2mdu 2222 10 on on IN cord-014597-66vd2mdu 2222 11 productivity productivity NN cord-014597-66vd2mdu 2222 12 . . . cord-014597-66vd2mdu 2223 1 -Lysis -lysis NN cord-014597-66vd2mdu 2224 1 : : : cord-014597-66vd2mdu 2224 2 Use Use NNP cord-014597-66vd2mdu 2224 3 of of IN cord-014597-66vd2mdu 2224 4 Trion Trion NNP cord-014597-66vd2mdu 2224 5 x-100 x-100 NNS cord-014597-66vd2mdu 2224 6 at at IN cord-014597-66vd2mdu 2224 7 0.5 0.5 CD cord-014597-66vd2mdu 2224 8 % % NN cord-014597-66vd2mdu 2224 9 with with IN cord-014597-66vd2mdu 2224 10 100 100 CD cord-014597-66vd2mdu 2224 11 mM mm CD cord-014597-66vd2mdu 2224 12 NaCl nacl NN cord-014597-66vd2mdu 2224 13 at at IN cord-014597-66vd2mdu 2224 14 pH pH NNP cord-014597-66vd2mdu 2224 15 8 8 CD cord-014597-66vd2mdu 2224 16 resulted result VBD cord-014597-66vd2mdu 2224 17 in in IN cord-014597-66vd2mdu 2224 18 > > XX cord-014597-66vd2mdu 2224 19 100 100 CD cord-014597-66vd2mdu 2224 20 % % NN cord-014597-66vd2mdu 2224 21 virus virus NN cord-014597-66vd2mdu 2224 22 recovery recovery NN cord-014597-66vd2mdu 2224 23 compared compare VBN cord-014597-66vd2mdu 2224 24 to to IN cord-014597-66vd2mdu 2224 25 sampled sample VBN cord-014597-66vd2mdu 2224 26 carriers carrier NNS cord-014597-66vd2mdu 2224 27 . . . cord-014597-66vd2mdu 2225 1 -Scaling -scale VBG cord-014597-66vd2mdu 2225 2 : : : cord-014597-66vd2mdu 2225 3 Specific specific JJ cord-014597-66vd2mdu 2225 4 productivity productivity NN cord-014597-66vd2mdu 2225 5 was be VBD cord-014597-66vd2mdu 2225 6 maintained maintain VBN cord-014597-66vd2mdu 2225 7 as as IN cord-014597-66vd2mdu 2225 8 the the DT cord-014597-66vd2mdu 2225 9 system system NN cord-014597-66vd2mdu 2225 10 was be VBD cord-014597-66vd2mdu 2225 11 scaled scale VBN cord-014597-66vd2mdu 2225 12 from from IN cord-014597-66vd2mdu 2225 13 0.8 0.8 CD cord-014597-66vd2mdu 2225 14 m m CD cord-014597-66vd2mdu 2225 15 2 2 CD cord-014597-66vd2mdu 2225 16 to to IN cord-014597-66vd2mdu 2225 17 4.0 4.0 CD cord-014597-66vd2mdu 2225 18 m m CD cord-014597-66vd2mdu 2225 19 2 2 CD cord-014597-66vd2mdu 2225 20 . . . cord-014597-66vd2mdu 2226 1 -Overall -overall UH cord-014597-66vd2mdu 2226 2 , , , cord-014597-66vd2mdu 2226 3 an an DT cord-014597-66vd2mdu 2226 4 average average JJ cord-014597-66vd2mdu 2226 5 yield yield NN cord-014597-66vd2mdu 2226 6 of of IN cord-014597-66vd2mdu 2226 7 4x10 4x10 CD cord-014597-66vd2mdu 2226 8 13 13 CD cord-014597-66vd2mdu 2226 9 VG VG NNP cord-014597-66vd2mdu 2226 10 / / SYM cord-014597-66vd2mdu 2226 11 m m NN cord-014597-66vd2mdu 2226 12 2 2 CD cord-014597-66vd2mdu 2226 13 was be VBD cord-014597-66vd2mdu 2226 14 achieved achieve VBN cord-014597-66vd2mdu 2226 15 . . . cord-014597-66vd2mdu 2227 1 The the DT cord-014597-66vd2mdu 2227 2 iCELLis iCELLis NNP cord-014597-66vd2mdu 2227 3 technology technology NN cord-014597-66vd2mdu 2227 4 is be VBZ cord-014597-66vd2mdu 2227 5 being be VBG cord-014597-66vd2mdu 2227 6 adopted adopt VBN cord-014597-66vd2mdu 2227 7 widely widely RB cord-014597-66vd2mdu 2227 8 for for IN cord-014597-66vd2mdu 2227 9 viral viral JJ cord-014597-66vd2mdu 2227 10 vector vector NN cord-014597-66vd2mdu 2227 11 production production NN cord-014597-66vd2mdu 2227 12 . . . cord-014597-66vd2mdu 2228 1 Transferring transfer VBG cord-014597-66vd2mdu 2228 2 a a DT cord-014597-66vd2mdu 2228 3 process process NN cord-014597-66vd2mdu 2228 4 to to IN cord-014597-66vd2mdu 2228 5 the the DT cord-014597-66vd2mdu 2228 6 iCELLis iCELLis NNP cord-014597-66vd2mdu 2228 7 Nano Nano NNP cord-014597-66vd2mdu 2228 8 bioreactor bioreactor NN cord-014597-66vd2mdu 2228 9 can can MD cord-014597-66vd2mdu 2228 10 be be VB cord-014597-66vd2mdu 2228 11 easily easily RB cord-014597-66vd2mdu 2228 12 achieved achieve VBN cord-014597-66vd2mdu 2228 13 and and CC cord-014597-66vd2mdu 2228 14 once once RB cord-014597-66vd2mdu 2228 15 in in IN cord-014597-66vd2mdu 2228 16 place place NN cord-014597-66vd2mdu 2228 17 can can MD cord-014597-66vd2mdu 2228 18 be be VB cord-014597-66vd2mdu 2228 19 optimized optimize VBN cord-014597-66vd2mdu 2228 20 to to TO cord-014597-66vd2mdu 2228 21 provide provide VB cord-014597-66vd2mdu 2228 22 significant significant JJ cord-014597-66vd2mdu 2228 23 productivity productivity NN cord-014597-66vd2mdu 2228 24 increases increase NNS cord-014597-66vd2mdu 2228 25 and and CC cord-014597-66vd2mdu 2228 26 cost cost NN cord-014597-66vd2mdu 2228 27 savings saving NNS cord-014597-66vd2mdu 2228 28 such such JJ cord-014597-66vd2mdu 2228 29 as as IN cord-014597-66vd2mdu 2228 30 reduced reduce VBN cord-014597-66vd2mdu 2228 31 pDNA pdna RB cord-014597-66vd2mdu 2228 32 . . . cord-014597-66vd2mdu 2229 1 The the DT cord-014597-66vd2mdu 2229 2 iCELLis iCELLis NNP cord-014597-66vd2mdu 2229 3 Nano Nano NNP cord-014597-66vd2mdu 2229 4 bioreactor bioreactor NN cord-014597-66vd2mdu 2229 5 is be VBZ cord-014597-66vd2mdu 2229 6 an an DT cord-014597-66vd2mdu 2229 7 efficient efficient JJ cord-014597-66vd2mdu 2229 8 bench bench NN cord-014597-66vd2mdu 2229 9 - - HYPH cord-014597-66vd2mdu 2229 10 top top NN cord-014597-66vd2mdu 2229 11 system system NN cord-014597-66vd2mdu 2229 12 the the DT cord-014597-66vd2mdu 2229 13 results result NNS cord-014597-66vd2mdu 2229 14 of of IN cord-014597-66vd2mdu 2229 15 which which WDT cord-014597-66vd2mdu 2229 16 can can MD cord-014597-66vd2mdu 2229 17 be be VB cord-014597-66vd2mdu 2229 18 readily readily RB cord-014597-66vd2mdu 2229 19 scaled scale VBN cord-014597-66vd2mdu 2229 20 to to IN cord-014597-66vd2mdu 2229 21 the the DT cord-014597-66vd2mdu 2229 22 iCELLis iCELLis NNP cord-014597-66vd2mdu 2229 23 500 500 CD cord-014597-66vd2mdu 2229 24 system system NN cord-014597-66vd2mdu 2229 25 . . . cord-014597-66vd2mdu 2230 1 Background Background NNP cord-014597-66vd2mdu 2230 2 TissUse TissUse NNP cord-014597-66vd2mdu 2230 3 Multi Multi NNP cord-014597-66vd2mdu 2230 4 - - HYPH cord-014597-66vd2mdu 2230 5 Organ Organ NNP cord-014597-66vd2mdu 2230 6 - - HYPH cord-014597-66vd2mdu 2230 7 Chip Chip NNP cord-014597-66vd2mdu 2230 8 ( ( -LRB- cord-014597-66vd2mdu 2230 9 MOC MOC NNP cord-014597-66vd2mdu 2230 10 ) ) -RRB- cord-014597-66vd2mdu 2230 11 platform platform NN cord-014597-66vd2mdu 2230 12 contributes contribute VBZ cord-014597-66vd2mdu 2230 13 to to IN cord-014597-66vd2mdu 2230 14 the the DT cord-014597-66vd2mdu 2230 15 ongoing ongoing JJ cord-014597-66vd2mdu 2230 16 advancement advancement NN cord-014597-66vd2mdu 2230 17 in in IN cord-014597-66vd2mdu 2230 18 systemic systemic JJ cord-014597-66vd2mdu 2230 19 substance substance NN cord-014597-66vd2mdu 2230 20 testing testing NN cord-014597-66vd2mdu 2230 21 in in IN cord-014597-66vd2mdu 2230 22 vitro vitro FW cord-014597-66vd2mdu 2230 23 . . . cord-014597-66vd2mdu 2231 1 Current current JJ cord-014597-66vd2mdu 2231 2 in in IN cord-014597-66vd2mdu 2231 3 vitro vitro FW cord-014597-66vd2mdu 2231 4 and and CC cord-014597-66vd2mdu 2231 5 animal animal NN cord-014597-66vd2mdu 2231 6 tests test NNS cord-014597-66vd2mdu 2231 7 for for IN cord-014597-66vd2mdu 2231 8 drug drug NN cord-014597-66vd2mdu 2231 9 development development NN cord-014597-66vd2mdu 2231 10 are be VBP cord-014597-66vd2mdu 2231 11 failing fail VBG cord-014597-66vd2mdu 2231 12 to to TO cord-014597-66vd2mdu 2231 13 emulate emulate VB cord-014597-66vd2mdu 2231 14 the the DT cord-014597-66vd2mdu 2231 15 systemic systemic JJ cord-014597-66vd2mdu 2231 16 organ organ NN cord-014597-66vd2mdu 2231 17 complexity complexity NN cord-014597-66vd2mdu 2231 18 of of IN cord-014597-66vd2mdu 2231 19 the the DT cord-014597-66vd2mdu 2231 20 human human JJ cord-014597-66vd2mdu 2231 21 body body NN cord-014597-66vd2mdu 2231 22 and and CC cord-014597-66vd2mdu 2231 23 , , , cord-014597-66vd2mdu 2231 24 therefore therefore RB cord-014597-66vd2mdu 2231 25 , , , cord-014597-66vd2mdu 2231 26 often often RB cord-014597-66vd2mdu 2231 27 do do VBP cord-014597-66vd2mdu 2231 28 not not RB cord-014597-66vd2mdu 2231 29 accurately accurately RB cord-014597-66vd2mdu 2231 30 predict predict VB cord-014597-66vd2mdu 2231 31 drug drug NN cord-014597-66vd2mdu 2231 32 toxicity toxicity NN cord-014597-66vd2mdu 2231 33 . . . cord-014597-66vd2mdu 2232 1 Especially especially RB cord-014597-66vd2mdu 2232 2 , , , cord-014597-66vd2mdu 2232 3 cardiotoxicity cardiotoxicity NN cord-014597-66vd2mdu 2232 4 is be VBZ cord-014597-66vd2mdu 2232 5 one one CD cord-014597-66vd2mdu 2232 6 of of IN cord-014597-66vd2mdu 2232 7 the the DT cord-014597-66vd2mdu 2232 8 main main JJ cord-014597-66vd2mdu 2232 9 reasons reason NNS cord-014597-66vd2mdu 2232 10 why why WRB cord-014597-66vd2mdu 2232 11 new new JJ cord-014597-66vd2mdu 2232 12 compounds compound NNS cord-014597-66vd2mdu 2232 13 are be VBP cord-014597-66vd2mdu 2232 14 failing fail VBG cord-014597-66vd2mdu 2232 15 in in IN cord-014597-66vd2mdu 2232 16 clinical clinical JJ cord-014597-66vd2mdu 2232 17 trials trial NNS cord-014597-66vd2mdu 2232 18 . . . cord-014597-66vd2mdu 2233 1 Therefore therefore RB cord-014597-66vd2mdu 2233 2 , , , cord-014597-66vd2mdu 2233 3 we -PRON- PRP cord-014597-66vd2mdu 2233 4 aimed aim VBD cord-014597-66vd2mdu 2233 5 to to TO cord-014597-66vd2mdu 2233 6 establish establish VB cord-014597-66vd2mdu 2233 7 an an DT cord-014597-66vd2mdu 2233 8 autologous autologous JJ cord-014597-66vd2mdu 2233 9 dynamic dynamic JJ cord-014597-66vd2mdu 2233 10 multiorgan multiorgan NN cord-014597-66vd2mdu 2233 11 - - HYPH cord-014597-66vd2mdu 2233 12 device device NN cord-014597-66vd2mdu 2233 13 integrating integrate VBG cord-014597-66vd2mdu 2233 14 cardiomyocytes cardiomyocyte NNS cord-014597-66vd2mdu 2233 15 for for IN cord-014597-66vd2mdu 2233 16 substance substance NN cord-014597-66vd2mdu 2233 17 testing testing NN cord-014597-66vd2mdu 2233 18 . . . cord-014597-66vd2mdu 2234 1 Generic generic JJ cord-014597-66vd2mdu 2234 2 2D 2d NN cord-014597-66vd2mdu 2234 3 monolayer monolayer NN cord-014597-66vd2mdu 2234 4 and and CC cord-014597-66vd2mdu 2234 5 3D 3D NNP cord-014597-66vd2mdu 2234 6 suspension suspension NN cord-014597-66vd2mdu 2234 7 iPSC iPSC NNP cord-014597-66vd2mdu 2234 8 derived derive VBN cord-014597-66vd2mdu 2234 9 cardiomyocytes cardiomyocyte NNS cord-014597-66vd2mdu 2234 10 differentiation differentiation NN cord-014597-66vd2mdu 2234 11 protocols protocol NNS cord-014597-66vd2mdu 2234 12 were be VBD cord-014597-66vd2mdu 2234 13 established establish VBN cord-014597-66vd2mdu 2234 14 . . . cord-014597-66vd2mdu 2235 1 Beating beat VBG cord-014597-66vd2mdu 2235 2 cardiomyocytes cardiomyocyte NNS cord-014597-66vd2mdu 2235 3 were be VBD cord-014597-66vd2mdu 2235 4 first first RB cord-014597-66vd2mdu 2235 5 seen see VBN cord-014597-66vd2mdu 2235 6 on on IN cord-014597-66vd2mdu 2235 7 day day NN cord-014597-66vd2mdu 2235 8 8 8 CD cord-014597-66vd2mdu 2235 9 in in IN cord-014597-66vd2mdu 2235 10 monolayer monolayer NN cord-014597-66vd2mdu 2235 11 as as RB cord-014597-66vd2mdu 2235 12 well well RB cord-014597-66vd2mdu 2235 13 as as IN cord-014597-66vd2mdu 2235 14 in in IN cord-014597-66vd2mdu 2235 15 spheroid spheroid NN cord-014597-66vd2mdu 2235 16 culture culture NN cord-014597-66vd2mdu 2235 17 . . . cord-014597-66vd2mdu 2236 1 Cardiomyocytes cardiomyocyte NNS cord-014597-66vd2mdu 2236 2 show show VBP cord-014597-66vd2mdu 2236 3 up up RP cord-014597-66vd2mdu 2236 4 to to TO cord-014597-66vd2mdu 2236 5 64 64 CD cord-014597-66vd2mdu 2236 6 % % NN cord-014597-66vd2mdu 2236 7 cardiac cardiac NN cord-014597-66vd2mdu 2236 8 troponin troponin VBD cord-014597-66vd2mdu 2236 9 T T NNP cord-014597-66vd2mdu 2236 10 positive positive JJ cord-014597-66vd2mdu 2236 11 cells cell NNS cord-014597-66vd2mdu 2236 12 and and CC cord-014597-66vd2mdu 2236 13 44 44 CD cord-014597-66vd2mdu 2236 14 % % NN cord-014597-66vd2mdu 2236 15 myosin myosin NN cord-014597-66vd2mdu 2236 16 heavy heavy JJ cord-014597-66vd2mdu 2236 17 chain chain NN cord-014597-66vd2mdu 2236 18 positive positive JJ cord-014597-66vd2mdu 2236 19 cells cell NNS cord-014597-66vd2mdu 2236 20 by by IN cord-014597-66vd2mdu 2236 21 flow flow NN cord-014597-66vd2mdu 2236 22 cytometry cytometry NN cord-014597-66vd2mdu 2236 23 ( ( -LRB- cord-014597-66vd2mdu 2236 24 Fig fig NN cord-014597-66vd2mdu 2236 25 . . . cord-014597-66vd2mdu 2236 26 1 1 CD cord-014597-66vd2mdu 2236 27 g g NN cord-014597-66vd2mdu 2236 28 , , , cord-014597-66vd2mdu 2236 29 h h NNP cord-014597-66vd2mdu 2236 30 ) ) -RRB- cord-014597-66vd2mdu 2236 31 . . . cord-014597-66vd2mdu 2237 1 Myosin myosin NN cord-014597-66vd2mdu 2237 2 II II NNP cord-014597-66vd2mdu 2237 3 heavy heavy JJ cord-014597-66vd2mdu 2237 4 chain chain NN cord-014597-66vd2mdu 2237 5 , , , cord-014597-66vd2mdu 2237 6 α α NN cord-014597-66vd2mdu 2237 7 - - HYPH cord-014597-66vd2mdu 2237 8 actinin actinin NNP cord-014597-66vd2mdu 2237 9 , , , cord-014597-66vd2mdu 2237 10 myosin myosin NN cord-014597-66vd2mdu 2237 11 9/10 9/10 CD cord-014597-66vd2mdu 2237 12 , , , cord-014597-66vd2mdu 2237 13 myosin myosin NN cord-014597-66vd2mdu 2237 14 11 11 CD cord-014597-66vd2mdu 2237 15 and and CC cord-014597-66vd2mdu 2237 16 caldesmon caldesmon JJ cord-014597-66vd2mdu 2237 17 expression expression NN cord-014597-66vd2mdu 2237 18 was be VBD cord-014597-66vd2mdu 2237 19 shown show VBN cord-014597-66vd2mdu 2237 20 by by IN cord-014597-66vd2mdu 2237 21 immunohistochemistry immunohistochemistry FW cord-014597-66vd2mdu 2237 22 ( ( -LRB- cord-014597-66vd2mdu 2237 23 Fig Fig NNP cord-014597-66vd2mdu 2237 24 . . . cord-014597-66vd2mdu 2237 25 1a 1a CD cord-014597-66vd2mdu 2237 26 - - HYPH cord-014597-66vd2mdu 2237 27 d d NN cord-014597-66vd2mdu 2237 28 ) ) -RRB- cord-014597-66vd2mdu 2237 29 . . . cord-014597-66vd2mdu 2238 1 Due due IN cord-014597-66vd2mdu 2238 2 to to IN cord-014597-66vd2mdu 2238 3 the the DT cord-014597-66vd2mdu 2238 4 exclusion exclusion NN cord-014597-66vd2mdu 2238 5 of of IN cord-014597-66vd2mdu 2238 6 a a DT cord-014597-66vd2mdu 2238 7 lactate lactate NN cord-014597-66vd2mdu 2238 8 enrichment enrichment NN cord-014597-66vd2mdu 2238 9 of of IN cord-014597-66vd2mdu 2238 10 cardiomyocytes cardiomyocyte NNS cord-014597-66vd2mdu 2238 11 , , , cord-014597-66vd2mdu 2238 12 cardiac cardiac JJ cord-014597-66vd2mdu 2238 13 fibroblasts fibroblast NNS cord-014597-66vd2mdu 2238 14 are be VBP cord-014597-66vd2mdu 2238 15 also also RB cord-014597-66vd2mdu 2238 16 expressed express VBN cord-014597-66vd2mdu 2238 17 in in IN cord-014597-66vd2mdu 2238 18 the the DT cord-014597-66vd2mdu 2238 19 spheroids spheroid NNS cord-014597-66vd2mdu 2238 20 shown show VBN cord-014597-66vd2mdu 2238 21 by by IN cord-014597-66vd2mdu 2238 22 vimentin vimentin NN cord-014597-66vd2mdu 2238 23 staining staining NN cord-014597-66vd2mdu 2238 24 . . . cord-014597-66vd2mdu 2239 1 Those those DT cord-014597-66vd2mdu 2239 2 cardiac cardiac JJ cord-014597-66vd2mdu 2239 3 fibroblasts fibroblast NNS cord-014597-66vd2mdu 2239 4 lead lead VBP cord-014597-66vd2mdu 2239 5 to to IN cord-014597-66vd2mdu 2239 6 a a DT cord-014597-66vd2mdu 2239 7 physiological physiological JJ cord-014597-66vd2mdu 2239 8 heterologous heterologous JJ cord-014597-66vd2mdu 2239 9 cell cell NN cord-014597-66vd2mdu 2239 10 population population NN cord-014597-66vd2mdu 2239 11 similar similar JJ cord-014597-66vd2mdu 2239 12 to to IN cord-014597-66vd2mdu 2239 13 the the DT cord-014597-66vd2mdu 2239 14 human human JJ cord-014597-66vd2mdu 2239 15 heart heart NN cord-014597-66vd2mdu 2239 16 . . . cord-014597-66vd2mdu 2240 1 Beating beat VBG cord-014597-66vd2mdu 2240 2 spheroids spheroid NNS cord-014597-66vd2mdu 2240 3 were be VBD cord-014597-66vd2mdu 2240 4 cultivated cultivate VBN cord-014597-66vd2mdu 2240 5 for for IN cord-014597-66vd2mdu 2240 6 7 7 CD cord-014597-66vd2mdu 2240 7 days day NNS cord-014597-66vd2mdu 2240 8 under under IN cord-014597-66vd2mdu 2240 9 dynamic dynamic JJ cord-014597-66vd2mdu 2240 10 culture culture NN cord-014597-66vd2mdu 2240 11 conditions condition NNS cord-014597-66vd2mdu 2240 12 in in IN cord-014597-66vd2mdu 2240 13 the the DT cord-014597-66vd2mdu 2240 14 Multi Multi NNP cord-014597-66vd2mdu 2240 15 - - NNP cord-014597-66vd2mdu 2240 16 Organ Organ NNP cord-014597-66vd2mdu 2240 17 - - HYPH cord-014597-66vd2mdu 2240 18 Chip Chip NNP cord-014597-66vd2mdu 2240 19 . . . cord-014597-66vd2mdu 2241 1 The the DT cord-014597-66vd2mdu 2241 2 integrated integrate VBN cord-014597-66vd2mdu 2241 3 on on IN cord-014597-66vd2mdu 2241 4 - - HYPH cord-014597-66vd2mdu 2241 5 chip chip NN cord-014597-66vd2mdu 2241 6 micropump micropump NN cord-014597-66vd2mdu 2241 7 provides provide VBZ cord-014597-66vd2mdu 2241 8 physiological physiological JJ cord-014597-66vd2mdu 2241 9 - - HYPH cord-014597-66vd2mdu 2241 10 like like JJ cord-014597-66vd2mdu 2241 11 pulsatile pulsatile JJ cord-014597-66vd2mdu 2241 12 circulation circulation NN cord-014597-66vd2mdu 2241 13 at at IN cord-014597-66vd2mdu 2241 14 a a DT cord-014597-66vd2mdu 2241 15 microliter microliter JJ cord-014597-66vd2mdu 2241 16 scale scale NN cord-014597-66vd2mdu 2241 17 and and CC cord-014597-66vd2mdu 2241 18 leads lead VBZ cord-014597-66vd2mdu 2241 19 to to IN cord-014597-66vd2mdu 2241 20 better well JJR cord-014597-66vd2mdu 2241 21 nutrition nutrition NN cord-014597-66vd2mdu 2241 22 and and CC cord-014597-66vd2mdu 2241 23 oxygen oxygen NN cord-014597-66vd2mdu 2241 24 supply supply NN cord-014597-66vd2mdu 2241 25 . . . cord-014597-66vd2mdu 2242 1 The the DT cord-014597-66vd2mdu 2242 2 next next JJ cord-014597-66vd2mdu 2242 3 significant significant JJ cord-014597-66vd2mdu 2242 4 step step NN cord-014597-66vd2mdu 2242 5 is be VBZ cord-014597-66vd2mdu 2242 6 to to TO cord-014597-66vd2mdu 2242 7 combine combine VB cord-014597-66vd2mdu 2242 8 multiple multiple JJ cord-014597-66vd2mdu 2242 9 autologous autologous JJ cord-014597-66vd2mdu 2242 10 3D 3d JJ cord-014597-66vd2mdu 2242 11 organ organ NN cord-014597-66vd2mdu 2242 12 equivalents equivalent NNS cord-014597-66vd2mdu 2242 13 in in IN cord-014597-66vd2mdu 2242 14 our -PRON- PRP$ cord-014597-66vd2mdu 2242 15 Multi multi JJ cord-014597-66vd2mdu 2242 16 - - HYPH cord-014597-66vd2mdu 2242 17 Organ Organ NNP cord-014597-66vd2mdu 2242 18 - - HYPH cord-014597-66vd2mdu 2242 19 Chip Chip NNP cord-014597-66vd2mdu 2242 20 using use VBG cord-014597-66vd2mdu 2242 21 iPSC ipsc JJ cord-014597-66vd2mdu 2242 22 differentiation differentiation NN cord-014597-66vd2mdu 2242 23 technology technology NN cord-014597-66vd2mdu 2242 24 . . . cord-014597-66vd2mdu 2243 1 Differentiating differentiate VBG cord-014597-66vd2mdu 2243 2 all all DT cord-014597-66vd2mdu 2243 3 cell cell NN cord-014597-66vd2mdu 2243 4 types type NNS cord-014597-66vd2mdu 2243 5 from from IN cord-014597-66vd2mdu 2243 6 one one CD cord-014597-66vd2mdu 2243 7 iPSC ipsc JJ cord-014597-66vd2mdu 2243 8 donor donor NN cord-014597-66vd2mdu 2243 9 is be VBZ cord-014597-66vd2mdu 2243 10 crucial crucial JJ cord-014597-66vd2mdu 2243 11 to to TO cord-014597-66vd2mdu 2243 12 overcome overcome VB cord-014597-66vd2mdu 2243 13 source source NN cord-014597-66vd2mdu 2243 14 and and CC cord-014597-66vd2mdu 2243 15 rejection rejection NN cord-014597-66vd2mdu 2243 16 problems problem NNS cord-014597-66vd2mdu 2243 17 . . . cord-014597-66vd2mdu 2244 1 Combining combine VBG cord-014597-66vd2mdu 2244 2 our -PRON- PRP$ cord-014597-66vd2mdu 2244 3 Multi multi JJ cord-014597-66vd2mdu 2244 4 - - HYPH cord-014597-66vd2mdu 2244 5 Organ Organ NNP cord-014597-66vd2mdu 2244 6 - - HYPH cord-014597-66vd2mdu 2244 7 Chip Chip NNP cord-014597-66vd2mdu 2244 8 platform platform NN cord-014597-66vd2mdu 2244 9 with with IN cord-014597-66vd2mdu 2244 10 iPSC ipsc JJ cord-014597-66vd2mdu 2244 11 differentiation differentiation NN cord-014597-66vd2mdu 2244 12 technology technology NN cord-014597-66vd2mdu 2244 13 will will MD cord-014597-66vd2mdu 2244 14 eventually eventually RB cord-014597-66vd2mdu 2244 15 lead lead VB cord-014597-66vd2mdu 2244 16 to to IN cord-014597-66vd2mdu 2244 17 a a DT cord-014597-66vd2mdu 2244 18 personalized personalized JJ cord-014597-66vd2mdu 2244 19 system system NN cord-014597-66vd2mdu 2244 20 for for IN cord-014597-66vd2mdu 2244 21 drug drug NN cord-014597-66vd2mdu 2244 22 and and CC cord-014597-66vd2mdu 2244 23 substance substance NN cord-014597-66vd2mdu 2244 24 testing testing NN cord-014597-66vd2mdu 2244 25 . . . cord-014597-66vd2mdu 2245 1 Lab lab NN cord-014597-66vd2mdu 2245 2 as as IN cord-014597-66vd2mdu 2245 3 a a DT cord-014597-66vd2mdu 2245 4 service service NN cord-014597-66vd2mdu 2245 5 -automated -automated CD cord-014597-66vd2mdu 2245 6 cell cell NN cord-014597-66vd2mdu 2245 7 - - HYPH cord-014597-66vd2mdu 2245 8 based base VBN cord-014597-66vd2mdu 2245 9 assays assay NNS cord-014597-66vd2mdu 2245 10 Lena Lena NNP cord-014597-66vd2mdu 2245 11 Schober Schober NNP cord-014597-66vd2mdu 2245 12 , , , cord-014597-66vd2mdu 2245 13 Moriz Moriz NNP cord-014597-66vd2mdu 2245 14 Walter Walter NNP cord-014597-66vd2mdu 2245 15 , , , cord-014597-66vd2mdu 2245 16 Andrea Andrea NNP cord-014597-66vd2mdu 2245 17 Traube Traube NNP cord-014597-66vd2mdu 2245 18 Laboratory Laboratory NNP cord-014597-66vd2mdu 2245 19 Automation Automation NNP cord-014597-66vd2mdu 2245 20 and and CC cord-014597-66vd2mdu 2245 21 Biomanufacturing Biomanufacturing NNP cord-014597-66vd2mdu 2245 22 Engineering Engineering NNP cord-014597-66vd2mdu 2245 23 , , , cord-014597-66vd2mdu 2245 24 Fraunhofer Fraunhofer NNP cord-014597-66vd2mdu 2245 25 IPA IPA NNP cord-014597-66vd2mdu 2245 26 , , , cord-014597-66vd2mdu 2246 1 Stuttgart Stuttgart NNP cord-014597-66vd2mdu 2246 2 , , , cord-014597-66vd2mdu 2246 3 Germany Germany NNP cord-014597-66vd2mdu 2246 4 Correspondence Correspondence NNP cord-014597-66vd2mdu 2246 5 : : : cord-014597-66vd2mdu 2247 1 Lena Lena NNP cord-014597-66vd2mdu 2247 2 Schober Schober NNP cord-014597-66vd2mdu 2247 3 ( ( -LRB- cord-014597-66vd2mdu 2247 4 lena.schober@ipa.fraunhofer.de lena.schober@ipa.fraunhofer.de NNP cord-014597-66vd2mdu 2247 5 ) ) -RRB- cord-014597-66vd2mdu 2248 1 BMC BMC NNP cord-014597-66vd2mdu 2248 2 Proceedings Proceedings NNP cord-014597-66vd2mdu 2248 3 2018 2018 CD cord-014597-66vd2mdu 2248 4 , , , cord-014597-66vd2mdu 2249 1 12(Suppl 12(suppl CD cord-014597-66vd2mdu 2249 2 1):P-365 1):p-365 CD cord-014597-66vd2mdu 2250 1 Background background NN cord-014597-66vd2mdu 2251 1 The the DT cord-014597-66vd2mdu 2251 2 use use NN cord-014597-66vd2mdu 2251 3 of of IN cord-014597-66vd2mdu 2251 4 cell cell NN cord-014597-66vd2mdu 2251 5 - - HYPH cord-014597-66vd2mdu 2251 6 based base VBN cord-014597-66vd2mdu 2251 7 assays assay NNS cord-014597-66vd2mdu 2251 8 in in IN cord-014597-66vd2mdu 2251 9 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 2251 10 industry industry NN cord-014597-66vd2mdu 2251 11 and and CC cord-014597-66vd2mdu 2251 12 academic academic JJ cord-014597-66vd2mdu 2251 13 research research NN cord-014597-66vd2mdu 2251 14 is be VBZ cord-014597-66vd2mdu 2251 15 a a DT cord-014597-66vd2mdu 2251 16 growing grow VBG cord-014597-66vd2mdu 2251 17 trend trend NN cord-014597-66vd2mdu 2251 18 that that WDT cord-014597-66vd2mdu 2251 19 is be VBZ cord-014597-66vd2mdu 2251 20 a a DT cord-014597-66vd2mdu 2251 21 driving drive VBG cord-014597-66vd2mdu 2251 22 force force NN cord-014597-66vd2mdu 2251 23 to to TO cord-014597-66vd2mdu 2251 24 reduce reduce VB cord-014597-66vd2mdu 2251 25 costs cost NNS cord-014597-66vd2mdu 2251 26 for for IN cord-014597-66vd2mdu 2251 27 drug drug NN cord-014597-66vd2mdu 2251 28 development development NN cord-014597-66vd2mdu 2251 29 . . . cord-014597-66vd2mdu 2252 1 Academic academic JJ cord-014597-66vd2mdu 2252 2 research research NN cord-014597-66vd2mdu 2252 3 is be VBZ cord-014597-66vd2mdu 2252 4 gaining gain VBG cord-014597-66vd2mdu 2252 5 information information NN cord-014597-66vd2mdu 2252 6 about about IN cord-014597-66vd2mdu 2252 7 intracellular intracellular JJ cord-014597-66vd2mdu 2252 8 targets target NNS cord-014597-66vd2mdu 2252 9 or or CC cord-014597-66vd2mdu 2252 10 functional functional JJ cord-014597-66vd2mdu 2252 11 mechanisms mechanism NNS cord-014597-66vd2mdu 2252 12 through through IN cord-014597-66vd2mdu 2252 13 the the DT cord-014597-66vd2mdu 2252 14 variety variety NN cord-014597-66vd2mdu 2252 15 of of IN cord-014597-66vd2mdu 2252 16 different different JJ cord-014597-66vd2mdu 2252 17 assays assay NNS cord-014597-66vd2mdu 2252 18 . . . cord-014597-66vd2mdu 2253 1 These these DT cord-014597-66vd2mdu 2253 2 benefits benefit NNS cord-014597-66vd2mdu 2253 3 can can MD cord-014597-66vd2mdu 2253 4 be be VB cord-014597-66vd2mdu 2253 5 used use VBN cord-014597-66vd2mdu 2253 6 in in IN cord-014597-66vd2mdu 2253 7 preclinical preclinical JJ cord-014597-66vd2mdu 2253 8 studies study NNS cord-014597-66vd2mdu 2253 9 and and CC cord-014597-66vd2mdu 2253 10 furthermore furthermore RB cord-014597-66vd2mdu 2253 11 costly costly JJ cord-014597-66vd2mdu 2253 12 late late JJ cord-014597-66vd2mdu 2253 13 - - HYPH cord-014597-66vd2mdu 2253 14 stage stage NN cord-014597-66vd2mdu 2253 15 drug drug NN cord-014597-66vd2mdu 2253 16 failures failure NNS cord-014597-66vd2mdu 2253 17 may may MD cord-014597-66vd2mdu 2253 18 be be VB cord-014597-66vd2mdu 2253 19 reduced reduce VBN cord-014597-66vd2mdu 2253 20 by by IN cord-014597-66vd2mdu 2253 21 the the DT cord-014597-66vd2mdu 2253 22 use use NN cord-014597-66vd2mdu 2253 23 of of IN cord-014597-66vd2mdu 2253 24 cell cell NN cord-014597-66vd2mdu 2253 25 - - HYPH cord-014597-66vd2mdu 2253 26 based base VBN cord-014597-66vd2mdu 2253 27 assays assay NNS cord-014597-66vd2mdu 2253 28 . . . cord-014597-66vd2mdu 2254 1 The the DT cord-014597-66vd2mdu 2254 2 use use NN cord-014597-66vd2mdu 2254 3 of of IN cord-014597-66vd2mdu 2254 4 automated automate VBN cord-014597-66vd2mdu 2254 5 systems system NNS cord-014597-66vd2mdu 2254 6 is be VBZ cord-014597-66vd2mdu 2254 7 also also RB cord-014597-66vd2mdu 2254 8 in in IN cord-014597-66vd2mdu 2254 9 great great JJ cord-014597-66vd2mdu 2254 10 demand demand NN cord-014597-66vd2mdu 2254 11 and and CC cord-014597-66vd2mdu 2254 12 will will MD cord-014597-66vd2mdu 2254 13 change change VB cord-014597-66vd2mdu 2254 14 the the DT cord-014597-66vd2mdu 2254 15 testing testing NN cord-014597-66vd2mdu 2254 16 of of IN cord-014597-66vd2mdu 2254 17 substances substance NNS cord-014597-66vd2mdu 2254 18 and and CC cord-014597-66vd2mdu 2254 19 research research NN cord-014597-66vd2mdu 2254 20 activities activity NNS cord-014597-66vd2mdu 2254 21 . . . cord-014597-66vd2mdu 2255 1 Nevertheless nevertheless RB cord-014597-66vd2mdu 2255 2 , , , cord-014597-66vd2mdu 2255 3 there there EX cord-014597-66vd2mdu 2255 4 are be VBP cord-014597-66vd2mdu 2255 5 a a DT cord-014597-66vd2mdu 2255 6 lot lot NN cord-014597-66vd2mdu 2255 7 of of IN cord-014597-66vd2mdu 2255 8 barriers barrier NNS cord-014597-66vd2mdu 2255 9 at at IN cord-014597-66vd2mdu 2255 10 the the DT cord-014597-66vd2mdu 2255 11 moment moment NN cord-014597-66vd2mdu 2255 12 limiting limit VBG cord-014597-66vd2mdu 2255 13 the the DT cord-014597-66vd2mdu 2255 14 successful successful JJ cord-014597-66vd2mdu 2255 15 application application NN cord-014597-66vd2mdu 2255 16 of of IN cord-014597-66vd2mdu 2255 17 automated automate VBN cord-014597-66vd2mdu 2255 18 systems system NNS cord-014597-66vd2mdu 2255 19 in in IN cord-014597-66vd2mdu 2255 20 this this DT cord-014597-66vd2mdu 2255 21 field field NN cord-014597-66vd2mdu 2255 22 . . . cord-014597-66vd2mdu 2256 1 By by IN cord-014597-66vd2mdu 2256 2 the the DT cord-014597-66vd2mdu 2256 3 lack lack NN cord-014597-66vd2mdu 2256 4 of of IN cord-014597-66vd2mdu 2256 5 flexibility flexibility NN cord-014597-66vd2mdu 2256 6 and and CC cord-014597-66vd2mdu 2256 7 the the DT cord-014597-66vd2mdu 2256 8 demand demand NN cord-014597-66vd2mdu 2256 9 for for IN cord-014597-66vd2mdu 2256 10 skilled skilled JJ cord-014597-66vd2mdu 2256 11 computer computer NN cord-014597-66vd2mdu 2256 12 scientists scientist NNS cord-014597-66vd2mdu 2256 13 & & CC cord-014597-66vd2mdu 2256 14 engineers engineer NNS cord-014597-66vd2mdu 2256 15 just just RB cord-014597-66vd2mdu 2256 16 the the DT cord-014597-66vd2mdu 2256 17 two two CD cord-014597-66vd2mdu 2256 18 main main JJ cord-014597-66vd2mdu 2256 19 aspects aspect NNS cord-014597-66vd2mdu 2256 20 stated state VBN cord-014597-66vd2mdu 2256 21 by by IN cord-014597-66vd2mdu 2256 22 experts expert NNS cord-014597-66vd2mdu 2256 23 shall shall MD cord-014597-66vd2mdu 2256 24 be be VB cord-014597-66vd2mdu 2256 25 mentioned mention VBN cord-014597-66vd2mdu 2256 26 . . . cord-014597-66vd2mdu 2257 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2257 2 strong strong JJ cord-014597-66vd2mdu 2257 3 background background NN cord-014597-66vd2mdu 2257 4 on on IN cord-014597-66vd2mdu 2257 5 automated automated JJ cord-014597-66vd2mdu 2257 6 cell cell NN cord-014597-66vd2mdu 2257 7 culture culture NN cord-014597-66vd2mdu 2257 8 technologies technology NNS cord-014597-66vd2mdu 2257 9 and and CC cord-014597-66vd2mdu 2257 10 expertise expertise NN cord-014597-66vd2mdu 2257 11 , , , cord-014597-66vd2mdu 2257 12 gained gain VBN cord-014597-66vd2mdu 2257 13 in in IN cord-014597-66vd2mdu 2257 14 several several JJ cord-014597-66vd2mdu 2257 15 projects project NNS cord-014597-66vd2mdu 2257 16 , , , cord-014597-66vd2mdu 2257 17 let let VB cord-014597-66vd2mdu 2257 18 us -PRON- PRP cord-014597-66vd2mdu 2257 19 rethink rethink VB cord-014597-66vd2mdu 2257 20 the the DT cord-014597-66vd2mdu 2257 21 overall overall JJ cord-014597-66vd2mdu 2257 22 process process NN cord-014597-66vd2mdu 2257 23 chain chain NN cord-014597-66vd2mdu 2257 24 and and CC cord-014597-66vd2mdu 2257 25 overcome overcome VB cord-014597-66vd2mdu 2257 26 established establish VBD cord-014597-66vd2mdu 2257 27 principles principle NNS cord-014597-66vd2mdu 2257 28 . . . cord-014597-66vd2mdu 2258 1 A a DT cord-014597-66vd2mdu 2258 2 new new JJ cord-014597-66vd2mdu 2258 3 service service NN cord-014597-66vd2mdu 2258 4 orientated orientate VBN cord-014597-66vd2mdu 2258 5 platform platform NN cord-014597-66vd2mdu 2258 6 for for IN cord-014597-66vd2mdu 2258 7 the the DT cord-014597-66vd2mdu 2258 8 execution execution NN cord-014597-66vd2mdu 2258 9 of of IN cord-014597-66vd2mdu 2258 10 cell cell NN cord-014597-66vd2mdu 2258 11 - - HYPH cord-014597-66vd2mdu 2258 12 based base VBN cord-014597-66vd2mdu 2258 13 assays assay NNS cord-014597-66vd2mdu 2258 14 that that WDT cord-014597-66vd2mdu 2258 15 are be VBP cord-014597-66vd2mdu 2258 16 commonly commonly RB cord-014597-66vd2mdu 2258 17 used use VBN cord-014597-66vd2mdu 2258 18 will will MD cord-014597-66vd2mdu 2258 19 be be VB cord-014597-66vd2mdu 2258 20 introduced introduce VBN cord-014597-66vd2mdu 2258 21 . . . cord-014597-66vd2mdu 2259 1 The the DT cord-014597-66vd2mdu 2259 2 main main JJ cord-014597-66vd2mdu 2259 3 idea idea NN cord-014597-66vd2mdu 2259 4 is be VBZ cord-014597-66vd2mdu 2259 5 to to TO cord-014597-66vd2mdu 2259 6 give give VB cord-014597-66vd2mdu 2259 7 access access NN cord-014597-66vd2mdu 2259 8 to to IN cord-014597-66vd2mdu 2259 9 automated automate VBN cord-014597-66vd2mdu 2259 10 infrastructure infrastructure NN cord-014597-66vd2mdu 2259 11 for for IN cord-014597-66vd2mdu 2259 12 academic academic JJ cord-014597-66vd2mdu 2259 13 research research NN cord-014597-66vd2mdu 2259 14 or or CC cord-014597-66vd2mdu 2259 15 spin spin NN cord-014597-66vd2mdu 2259 16 - - HYPH cord-014597-66vd2mdu 2259 17 offs off NNS cord-014597-66vd2mdu 2259 18 which which WDT cord-014597-66vd2mdu 2259 19 can can MD cord-014597-66vd2mdu 2259 20 not not RB cord-014597-66vd2mdu 2259 21 afford afford VB cord-014597-66vd2mdu 2259 22 the the DT cord-014597-66vd2mdu 2259 23 special special JJ cord-014597-66vd2mdu 2259 24 infrastructure infrastructure NN cord-014597-66vd2mdu 2259 25 . . . cord-014597-66vd2mdu 2259 26 _SP cord-014597-66vd2mdu 2260 1 Nowadays nowadays RB cord-014597-66vd2mdu 2260 2 it -PRON- PRP cord-014597-66vd2mdu 2260 3 is be VBZ cord-014597-66vd2mdu 2260 4 known know VBN cord-014597-66vd2mdu 2260 5 that that IN cord-014597-66vd2mdu 2260 6 the the DT cord-014597-66vd2mdu 2260 7 development development NN cord-014597-66vd2mdu 2260 8 of of IN cord-014597-66vd2mdu 2260 9 inhibitory inhibitory JJ cord-014597-66vd2mdu 2260 10 antibodies antibody NNS cord-014597-66vd2mdu 2260 11 by by IN cord-014597-66vd2mdu 2260 12 hemophiliac hemophiliac NN cord-014597-66vd2mdu 2260 13 patients patient NNS cord-014597-66vd2mdu 2260 14 is be VBZ cord-014597-66vd2mdu 2260 15 closely closely RB cord-014597-66vd2mdu 2260 16 related relate VBN cord-014597-66vd2mdu 2260 17 with with IN cord-014597-66vd2mdu 2260 18 immunogenic immunogenic JJ cord-014597-66vd2mdu 2260 19 epitopes epitope NNS cord-014597-66vd2mdu 2260 20 present present JJ cord-014597-66vd2mdu 2260 21 in in IN cord-014597-66vd2mdu 2260 22 the the DT cord-014597-66vd2mdu 2260 23 coagulation coagulation NN cord-014597-66vd2mdu 2260 24 factors factor NNS cord-014597-66vd2mdu 2260 25 . . . cord-014597-66vd2mdu 2261 1 These these DT cord-014597-66vd2mdu 2261 2 proteins protein NNS cord-014597-66vd2mdu 2261 3 are be VBP cord-014597-66vd2mdu 2261 4 produced produce VBN cord-014597-66vd2mdu 2261 5 in in IN cord-014597-66vd2mdu 2261 6 hamsters hamster NNS cord-014597-66vd2mdu 2261 7 cells cell NNS cord-014597-66vd2mdu 2261 8 [ [ -LRB- cord-014597-66vd2mdu 2261 9 1 1 CD cord-014597-66vd2mdu 2261 10 -4 -4 CD cord-014597-66vd2mdu 2261 11 ] ] -RRB- cord-014597-66vd2mdu 2261 12 which which WDT cord-014597-66vd2mdu 2261 13 insert insert VBP cord-014597-66vd2mdu 2261 14 a a DT cord-014597-66vd2mdu 2261 15 different different JJ cord-014597-66vd2mdu 2261 16 posttranslational posttranslational JJ cord-014597-66vd2mdu 2261 17 modification modification NN cord-014597-66vd2mdu 2261 18 profile profile NN cord-014597-66vd2mdu 2261 19 when when WRB cord-014597-66vd2mdu 2261 20 compared compare VBN cord-014597-66vd2mdu 2261 21 with with IN cord-014597-66vd2mdu 2261 22 the the DT cord-014597-66vd2mdu 2261 23 human human JJ cord-014597-66vd2mdu 2261 24 profile profile NN cord-014597-66vd2mdu 2261 25 . . . cord-014597-66vd2mdu 2262 1 Patients patient NNS cord-014597-66vd2mdu 2262 2 with with IN cord-014597-66vd2mdu 2262 3 high high JJ cord-014597-66vd2mdu 2262 4 - - HYPH cord-014597-66vd2mdu 2262 5 titer titer NN cord-014597-66vd2mdu 2262 6 / / SYM cord-014597-66vd2mdu 2262 7 high high RB cord-014597-66vd2mdu 2262 8 - - HYPH cord-014597-66vd2mdu 2262 9 responding respond VBG cord-014597-66vd2mdu 2262 10 inhibitors inhibitor NNS cord-014597-66vd2mdu 2262 11 must must MD cord-014597-66vd2mdu 2262 12 be be VB cord-014597-66vd2mdu 2262 13 treated treat VBN cord-014597-66vd2mdu 2262 14 with with IN cord-014597-66vd2mdu 2262 15 bypassing bypass VBG cord-014597-66vd2mdu 2262 16 agents agent NNS cord-014597-66vd2mdu 2262 17 that that WDT cord-014597-66vd2mdu 2262 18 can can MD cord-014597-66vd2mdu 2262 19 achieve achieve VB cord-014597-66vd2mdu 2262 20 hemostasis hemostasis NN cord-014597-66vd2mdu 2262 21 . . . cord-014597-66vd2mdu 2263 1 Activated activate VBN cord-014597-66vd2mdu 2263 2 factor factor NN cord-014597-66vd2mdu 2263 3 VII vii NN cord-014597-66vd2mdu 2263 4 ( ( -LRB- cord-014597-66vd2mdu 2263 5 FVIIa FVIIa NNS cord-014597-66vd2mdu 2263 6 ) ) -RRB- cord-014597-66vd2mdu 2263 7 is be VBZ cord-014597-66vd2mdu 2263 8 an an DT cord-014597-66vd2mdu 2263 9 attractive attractive JJ cord-014597-66vd2mdu 2263 10 candidate candidate NN cord-014597-66vd2mdu 2263 11 for for IN cord-014597-66vd2mdu 2263 12 hemostasis hemostasis NN cord-014597-66vd2mdu 2263 13 , , , cord-014597-66vd2mdu 2263 14 independent independent JJ cord-014597-66vd2mdu 2263 15 of of IN cord-014597-66vd2mdu 2263 16 FVIII FVIII NNP cord-014597-66vd2mdu 2263 17 / / SYM cord-014597-66vd2mdu 2263 18 FIX fix NN cord-014597-66vd2mdu 2263 19 , , , cord-014597-66vd2mdu 2263 20 making make VBG cord-014597-66vd2mdu 2263 21 this this DT cord-014597-66vd2mdu 2263 22 coagulation coagulation NN cord-014597-66vd2mdu 2263 23 factor factor NN cord-014597-66vd2mdu 2263 24 an an DT cord-014597-66vd2mdu 2263 25 alternative alternative NN cord-014597-66vd2mdu 2263 26 for for IN cord-014597-66vd2mdu 2263 27 hemophilia hemophilia NN cord-014597-66vd2mdu 2263 28 patients patient NNS cord-014597-66vd2mdu 2263 29 with with IN cord-014597-66vd2mdu 2263 30 inhibitory inhibitory JJ cord-014597-66vd2mdu 2263 31 antibodies antibody NNS cord-014597-66vd2mdu 2263 32 . . . cord-014597-66vd2mdu 2264 1 However however RB cord-014597-66vd2mdu 2264 2 recombinant recombinant JJ cord-014597-66vd2mdu 2264 3 factor factor NN cord-014597-66vd2mdu 2264 4 VII VII NNP cord-014597-66vd2mdu 2264 5 is be VBZ cord-014597-66vd2mdu 2264 6 produced produce VBN cord-014597-66vd2mdu 2264 7 in in IN cord-014597-66vd2mdu 2264 8 BHK-21 BHK-21 NNP cord-014597-66vd2mdu 2264 9 cells cell NNS cord-014597-66vd2mdu 2264 10 ( ( -LRB- cord-014597-66vd2mdu 2264 11 Baby Baby NNP cord-014597-66vd2mdu 2264 12 hamster hamster NN cord-014597-66vd2mdu 2264 13 kidney kidney NN cord-014597-66vd2mdu 2264 14 cells cell NNS cord-014597-66vd2mdu 2264 15 ) ) -RRB- cord-014597-66vd2mdu 2264 16 and and CC cord-014597-66vd2mdu 2264 17 as as RB cord-014597-66vd2mdu 2264 18 well well RB cord-014597-66vd2mdu 2264 19 as as IN cord-014597-66vd2mdu 2264 20 the the DT cord-014597-66vd2mdu 2264 21 others other NNS cord-014597-66vd2mdu 2264 22 coagulation coagulation NN cord-014597-66vd2mdu 2264 23 factors factor NNS cord-014597-66vd2mdu 2264 24 , , , cord-014597-66vd2mdu 2264 25 it -PRON- PRP cord-014597-66vd2mdu 2264 26 may may MD cord-014597-66vd2mdu 2264 27 contain contain VB cord-014597-66vd2mdu 2264 28 immunogenic immunogenic JJ cord-014597-66vd2mdu 2264 29 epitopes epitope NNS cord-014597-66vd2mdu 2264 30 [ [ -LRB- cord-014597-66vd2mdu 2264 31 5 5 CD cord-014597-66vd2mdu 2264 32 -7 -7 CD cord-014597-66vd2mdu 2264 33 ] ] -RRB- cord-014597-66vd2mdu 2264 34 . . . cord-014597-66vd2mdu 2265 1 In in IN cord-014597-66vd2mdu 2265 2 this this DT cord-014597-66vd2mdu 2265 3 context context NN cord-014597-66vd2mdu 2265 4 , , , cord-014597-66vd2mdu 2265 5 becomes become VBZ cord-014597-66vd2mdu 2265 6 extremely extremely RB cord-014597-66vd2mdu 2265 7 important important JJ cord-014597-66vd2mdu 2265 8 to to TO cord-014597-66vd2mdu 2265 9 produce produce VB cord-014597-66vd2mdu 2265 10 recombinant recombinant JJ cord-014597-66vd2mdu 2265 11 proteins protein NNS cord-014597-66vd2mdu 2265 12 with with IN cord-014597-66vd2mdu 2265 13 complex complex JJ cord-014597-66vd2mdu 2265 14 posttranslational posttranslational JJ cord-014597-66vd2mdu 2265 15 modifications modification NNS cord-014597-66vd2mdu 2265 16 in in IN cord-014597-66vd2mdu 2265 17 a a DT cord-014597-66vd2mdu 2265 18 cell cell NN cord-014597-66vd2mdu 2265 19 line line NN cord-014597-66vd2mdu 2265 20 not not RB cord-014597-66vd2mdu 2265 21 yet yet RB cord-014597-66vd2mdu 2265 22 used use VBN cord-014597-66vd2mdu 2265 23 [ [ -LRB- cord-014597-66vd2mdu 2265 24 8 8 CD cord-014597-66vd2mdu 2265 25 -10 -10 NN cord-014597-66vd2mdu 2265 26 ] ] -RRB- cord-014597-66vd2mdu 2265 27 . . . cord-014597-66vd2mdu 2266 1 We -PRON- PRP cord-014597-66vd2mdu 2266 2 have have VBP cord-014597-66vd2mdu 2266 3 been be VBN cord-014597-66vd2mdu 2266 4 using use VBG cord-014597-66vd2mdu 2266 5 the the DT cord-014597-66vd2mdu 2266 6 Sk Sk NNP cord-014597-66vd2mdu 2266 7 - - HYPH cord-014597-66vd2mdu 2266 8 Hep-1 Hep-1 NNP cord-014597-66vd2mdu 2266 9 human human JJ cord-014597-66vd2mdu 2266 10 cell cell NN cord-014597-66vd2mdu 2266 11 line line NN cord-014597-66vd2mdu 2266 12 for for IN cord-014597-66vd2mdu 2266 13 the the DT cord-014597-66vd2mdu 2266 14 production production NN cord-014597-66vd2mdu 2266 15 of of IN cord-014597-66vd2mdu 2266 16 recombinant recombinant JJ cord-014597-66vd2mdu 2266 17 FVII FVII NNP cord-014597-66vd2mdu 2266 18 . . . cord-014597-66vd2mdu 2267 1 To to TO cord-014597-66vd2mdu 2267 2 generate generate VB cord-014597-66vd2mdu 2267 3 the the DT cord-014597-66vd2mdu 2267 4 recombinant recombinant JJ cord-014597-66vd2mdu 2267 5 cell cell NN cord-014597-66vd2mdu 2267 6 line line NN cord-014597-66vd2mdu 2267 7 we -PRON- PRP cord-014597-66vd2mdu 2267 8 have have VBP cord-014597-66vd2mdu 2267 9 used use VBN cord-014597-66vd2mdu 2267 10 a a DT cord-014597-66vd2mdu 2267 11 bicistronic bicistronic JJ cord-014597-66vd2mdu 2267 12 lentiviral lentiviral JJ cord-014597-66vd2mdu 2267 13 vector vector NN cord-014597-66vd2mdu 2267 14 , , , cord-014597-66vd2mdu 2267 15 1054-GFP 1054-gfp CD cord-014597-66vd2mdu 2267 16 , , , cord-014597-66vd2mdu 2267 17 containing contain VBG cord-014597-66vd2mdu 2267 18 a a DT cord-014597-66vd2mdu 2267 19 FVII FVII NNP cord-014597-66vd2mdu 2267 20 gene gene NN cord-014597-66vd2mdu 2267 21 and and CC cord-014597-66vd2mdu 2267 22 the the DT cord-014597-66vd2mdu 2267 23 GFP GFP NNP cord-014597-66vd2mdu 2267 24 selection selection NN cord-014597-66vd2mdu 2267 25 marker marker NN cord-014597-66vd2mdu 2267 26 gene gene NN cord-014597-66vd2mdu 2267 27 . . . cord-014597-66vd2mdu 2268 1 A a DT cord-014597-66vd2mdu 2268 2 master master NN cord-014597-66vd2mdu 2268 3 cell cell NN cord-014597-66vd2mdu 2268 4 bank bank NN cord-014597-66vd2mdu 2268 5 and and CC cord-014597-66vd2mdu 2268 6 a a DT cord-014597-66vd2mdu 2268 7 work work NN cord-014597-66vd2mdu 2268 8 cell cell NN cord-014597-66vd2mdu 2268 9 bank bank NN cord-014597-66vd2mdu 2268 10 were be VBD cord-014597-66vd2mdu 2268 11 generated generate VBN cord-014597-66vd2mdu 2268 12 in in IN cord-014597-66vd2mdu 2268 13 GMP GMP NNP cord-014597-66vd2mdu 2268 14 conditions condition NNS cord-014597-66vd2mdu 2268 15 . . . cord-014597-66vd2mdu 2269 1 The the DT cord-014597-66vd2mdu 2269 2 rFVII rfvii NN cord-014597-66vd2mdu 2269 3 analyses analysis NNS cord-014597-66vd2mdu 2269 4 were be VBD cord-014597-66vd2mdu 2269 5 made make VBN cord-014597-66vd2mdu 2269 6 by by IN cord-014597-66vd2mdu 2269 7 ELISA ELISA NNP cord-014597-66vd2mdu 2269 8 assay assay NN cord-014597-66vd2mdu 2269 9 , , , cord-014597-66vd2mdu 2269 10 western western JJ cord-014597-66vd2mdu 2269 11 blot blot NN cord-014597-66vd2mdu 2269 12 , , , cord-014597-66vd2mdu 2269 13 gene gene NN cord-014597-66vd2mdu 2269 14 expression expression NN cord-014597-66vd2mdu 2269 15 quantification quantification NN cord-014597-66vd2mdu 2269 16 and and CC cord-014597-66vd2mdu 2269 17 biological biological JJ cord-014597-66vd2mdu 2269 18 activity activity NN cord-014597-66vd2mdu 2269 19 using use VBG cord-014597-66vd2mdu 2269 20 the the DT cord-014597-66vd2mdu 2269 21 Prothrombin Prothrombin NNP cord-014597-66vd2mdu 2269 22 Time Time NNP cord-014597-66vd2mdu 2269 23 ( ( -LRB- cord-014597-66vd2mdu 2269 24 PT PT NNP cord-014597-66vd2mdu 2269 25 ) ) -RRB- cord-014597-66vd2mdu 2269 26 assay assay NN cord-014597-66vd2mdu 2269 27 . . . cord-014597-66vd2mdu 2270 1 rFVII rFVII NNP cord-014597-66vd2mdu 2270 2 purification purification NN cord-014597-66vd2mdu 2270 3 by by IN cord-014597-66vd2mdu 2270 4 affinity affinity NN cord-014597-66vd2mdu 2270 5 chromatography chromatography NN cord-014597-66vd2mdu 2270 6 using use VBG cord-014597-66vd2mdu 2270 7 VIISelect VIISelect NNP cord-014597-66vd2mdu 2270 8 ( ( -LRB- cord-014597-66vd2mdu 2270 9 GE GE NNP cord-014597-66vd2mdu 2270 10 ) ) -RRB- cord-014597-66vd2mdu 2270 11 column column NN cord-014597-66vd2mdu 2270 12 . . . cord-014597-66vd2mdu 2271 1 After after IN cord-014597-66vd2mdu 2271 2 purification purification NN cord-014597-66vd2mdu 2271 3 the the DT cord-014597-66vd2mdu 2271 4 rFVII rfvii NN cord-014597-66vd2mdu 2271 5 was be VBD cord-014597-66vd2mdu 2271 6 formulated formulate VBN cord-014597-66vd2mdu 2271 7 and and CC cord-014597-66vd2mdu 2271 8 dry dry JJ cord-014597-66vd2mdu 2271 9 froze freeze VBN cord-014597-66vd2mdu 2271 10 to to TO cord-014597-66vd2mdu 2271 11 be be VB cord-014597-66vd2mdu 2271 12 used use VBN cord-014597-66vd2mdu 2271 13 in in IN cord-014597-66vd2mdu 2271 14 in in IN cord-014597-66vd2mdu 2271 15 vivo vivo NN cord-014597-66vd2mdu 2271 16 experiments experiment NNS cord-014597-66vd2mdu 2271 17 . . . cord-014597-66vd2mdu 2272 1 In in IN cord-014597-66vd2mdu 2272 2 static static JJ cord-014597-66vd2mdu 2272 3 conditions condition NNS cord-014597-66vd2mdu 2272 4 Sk Sk NNP cord-014597-66vd2mdu 2272 5 - - HYPH cord-014597-66vd2mdu 2272 6 Hep-1 Hep-1 NNP cord-014597-66vd2mdu 2272 7 cells cell NNS cord-014597-66vd2mdu 2272 8 showed show VBD cord-014597-66vd2mdu 2272 9 , , , cord-014597-66vd2mdu 2272 10 for for IN cord-014597-66vd2mdu 2272 11 a a DT cord-014597-66vd2mdu 2272 12 period period NN cord-014597-66vd2mdu 2272 13 of of IN cord-014597-66vd2mdu 2272 14 6 6 CD cord-014597-66vd2mdu 2272 15 months month NNS cord-014597-66vd2mdu 2272 16 , , , cord-014597-66vd2mdu 2272 17 a a DT cord-014597-66vd2mdu 2272 18 stable stable JJ cord-014597-66vd2mdu 2272 19 FVII FVII NNP cord-014597-66vd2mdu 2272 20 production production NN cord-014597-66vd2mdu 2272 21 with with IN cord-014597-66vd2mdu 2272 22 an an DT cord-014597-66vd2mdu 2272 23 average average NN cord-014597-66vd2mdu 2272 24 of of IN cord-014597-66vd2mdu 2272 25 8,03 8,03 CD cord-014597-66vd2mdu 2272 26 IU IU NNP cord-014597-66vd2mdu 2272 27 / / , cord-014597-66vd2mdu 2272 28 mL ml NN cord-014597-66vd2mdu 2272 29 of of IN cord-014597-66vd2mdu 2272 30 FVII FVII NNP cord-014597-66vd2mdu 2272 31 , , , cord-014597-66vd2mdu 2272 32 83 83 CD cord-014597-66vd2mdu 2272 33 % % NN cord-014597-66vd2mdu 2272 34 of of IN cord-014597-66vd2mdu 2272 35 cell cell NN cord-014597-66vd2mdu 2272 36 viability viability NN cord-014597-66vd2mdu 2272 37 and and CC cord-014597-66vd2mdu 2272 38 77 77 CD cord-014597-66vd2mdu 2272 39 % % NN cord-014597-66vd2mdu 2272 40 of of IN cord-014597-66vd2mdu 2272 41 cells cell NNS cord-014597-66vd2mdu 2272 42 expressing express VBG cord-014597-66vd2mdu 2272 43 the the DT cord-014597-66vd2mdu 2272 44 GFP GFP NNP cord-014597-66vd2mdu 2272 45 gene gene NN cord-014597-66vd2mdu 2272 46 . . . cord-014597-66vd2mdu 2273 1 After after IN cord-014597-66vd2mdu 2273 2 purification purification NN cord-014597-66vd2mdu 2273 3 with with IN cord-014597-66vd2mdu 2273 4 VIISelect viiselect JJ cord-014597-66vd2mdu 2273 5 column column NN cord-014597-66vd2mdu 2273 6 it -PRON- PRP cord-014597-66vd2mdu 2273 7 was be VBD cord-014597-66vd2mdu 2273 8 possible possible JJ cord-014597-66vd2mdu 2273 9 observe observe VB cord-014597-66vd2mdu 2273 10 a a DT cord-014597-66vd2mdu 2273 11 recover recover NN cord-014597-66vd2mdu 2273 12 of of IN cord-014597-66vd2mdu 2273 13 65 65 CD cord-014597-66vd2mdu 2273 14 % % NN cord-014597-66vd2mdu 2273 15 of of IN cord-014597-66vd2mdu 2273 16 the the DT cord-014597-66vd2mdu 2273 17 purified purify VBN cord-014597-66vd2mdu 2273 18 protein protein NN cord-014597-66vd2mdu 2273 19 with with IN cord-014597-66vd2mdu 2273 20 95 95 CD cord-014597-66vd2mdu 2273 21 % % NN cord-014597-66vd2mdu 2273 22 degree degree NN cord-014597-66vd2mdu 2273 23 of of IN cord-014597-66vd2mdu 2273 24 purity purity NN cord-014597-66vd2mdu 2273 25 ( ( -LRB- cord-014597-66vd2mdu 2273 26 Fig Fig NNP cord-014597-66vd2mdu 2273 27 . . . cord-014597-66vd2mdu 2273 28 1 1 CD cord-014597-66vd2mdu 2273 29 ) ) -RRB- cord-014597-66vd2mdu 2273 30 . . . cord-014597-66vd2mdu 2274 1 This this DT cord-014597-66vd2mdu 2274 2 recombinant recombinant JJ cord-014597-66vd2mdu 2274 3 purified purify VBN cord-014597-66vd2mdu 2274 4 FVII FVII NNP cord-014597-66vd2mdu 2274 5 is be VBZ cord-014597-66vd2mdu 2274 6 being be VBG cord-014597-66vd2mdu 2274 7 used use VBN cord-014597-66vd2mdu 2274 8 in in IN cord-014597-66vd2mdu 2274 9 in in IN cord-014597-66vd2mdu 2274 10 vivo vivo NN cord-014597-66vd2mdu 2274 11 experiments experiment NNS cord-014597-66vd2mdu 2274 12 to to TO cord-014597-66vd2mdu 2274 13 determine determine VB cord-014597-66vd2mdu 2274 14 the the DT cord-014597-66vd2mdu 2274 15 pharmacokinetics pharmacokinetic NNS cord-014597-66vd2mdu 2274 16 parameters parameter NNS cord-014597-66vd2mdu 2274 17 and and CC cord-014597-66vd2mdu 2274 18 to to TO cord-014597-66vd2mdu 2274 19 evaluate evaluate VB cord-014597-66vd2mdu 2274 20 the the DT cord-014597-66vd2mdu 2274 21 posttranslation posttranslation NN cord-014597-66vd2mdu 2274 22 modifications modification NNS cord-014597-66vd2mdu 2274 23 profile profile RB cord-014597-66vd2mdu 2274 24 . . . cord-014597-66vd2mdu 2275 1 In in IN cord-014597-66vd2mdu 2275 2 conclusion conclusion NN cord-014597-66vd2mdu 2275 3 , , , cord-014597-66vd2mdu 2275 4 this this DT cord-014597-66vd2mdu 2275 5 study study NN cord-014597-66vd2mdu 2275 6 reports report VBZ cord-014597-66vd2mdu 2275 7 the the DT cord-014597-66vd2mdu 2275 8 use use NN cord-014597-66vd2mdu 2275 9 of of IN cord-014597-66vd2mdu 2275 10 Sk Sk NNP cord-014597-66vd2mdu 2275 11 - - HYPH cord-014597-66vd2mdu 2275 12 Hep-1 Hep-1 NNP cord-014597-66vd2mdu 2275 13 cell cell NN cord-014597-66vd2mdu 2275 14 line line NN cord-014597-66vd2mdu 2275 15 for for IN cord-014597-66vd2mdu 2275 16 high high JJ cord-014597-66vd2mdu 2275 17 - - HYPH cord-014597-66vd2mdu 2275 18 level level NN cord-014597-66vd2mdu 2275 19 production production NN cord-014597-66vd2mdu 2275 20 of of IN cord-014597-66vd2mdu 2275 21 recombinant recombinant JJ cord-014597-66vd2mdu 2275 22 factor factor NN cord-014597-66vd2mdu 2275 23 VII VII NNP cord-014597-66vd2mdu 2275 24 . . . cord-014597-66vd2mdu 2276 1 These these DT cord-014597-66vd2mdu 2276 2 cells cell NNS cord-014597-66vd2mdu 2276 3 have have VBP cord-014597-66vd2mdu 2276 4 proven prove VBN cord-014597-66vd2mdu 2276 5 to to TO cord-014597-66vd2mdu 2276 6 be be VB cord-014597-66vd2mdu 2276 7 effective effective JJ cord-014597-66vd2mdu 2276 8 in in IN cord-014597-66vd2mdu 2276 9 the the DT cord-014597-66vd2mdu 2276 10 production production NN cord-014597-66vd2mdu 2276 11 of of IN cord-014597-66vd2mdu 2276 12 recombinant recombinant JJ cord-014597-66vd2mdu 2276 13 protein protein NN cord-014597-66vd2mdu 2276 14 and and CC cord-014597-66vd2mdu 2276 15 can can MD cord-014597-66vd2mdu 2276 16 be be VB cord-014597-66vd2mdu 2276 17 used use VBN cord-014597-66vd2mdu 2276 18 as as IN cord-014597-66vd2mdu 2276 19 a a DT cord-014597-66vd2mdu 2276 20 new new JJ cord-014597-66vd2mdu 2276 21 platform platform NN cord-014597-66vd2mdu 2276 22 for for IN cord-014597-66vd2mdu 2276 23 the the DT cord-014597-66vd2mdu 2276 24 production production NN cord-014597-66vd2mdu 2276 25 of of IN cord-014597-66vd2mdu 2276 26 recombinant recombinant JJ cord-014597-66vd2mdu 2276 27 proteins protein NNS cord-014597-66vd2mdu 2276 28 . . . cord-014597-66vd2mdu 2277 1 Fig Fig NNP cord-014597-66vd2mdu 2277 2 . . . cord-014597-66vd2mdu 2277 3 1 1 CD cord-014597-66vd2mdu 2277 4 ( ( -LRB- cord-014597-66vd2mdu 2277 5 abstract abstract NNP cord-014597-66vd2mdu 2277 6 P-366 P-366 NNP cord-014597-66vd2mdu 2277 7 ) ) -RRB- cord-014597-66vd2mdu 2277 8 . . . cord-014597-66vd2mdu 2278 1 a a DT cord-014597-66vd2mdu 2278 2 Determination determination NN cord-014597-66vd2mdu 2278 3 of of IN cord-014597-66vd2mdu 2278 4 protein protein NN cord-014597-66vd2mdu 2278 5 yield yield NN cord-014597-66vd2mdu 2278 6 of of IN cord-014597-66vd2mdu 2278 7 EGFR EGFR NNP cord-014597-66vd2mdu 2278 8 ( ( -LRB- cord-014597-66vd2mdu 2278 9 Epidermal epidermal JJ cord-014597-66vd2mdu 2278 10 growth growth NN cord-014597-66vd2mdu 2278 11 factor factor NN cord-014597-66vd2mdu 2278 12 receptor receptor NN cord-014597-66vd2mdu 2278 13 ) ) -RRB- cord-014597-66vd2mdu 2278 14 synthesized synthesize VBN cord-014597-66vd2mdu 2278 15 in in IN cord-014597-66vd2mdu 2278 16 a a DT cord-014597-66vd2mdu 2278 17 CHO CHO NNP cord-014597-66vd2mdu 2278 18 CECF CECF NNP cord-014597-66vd2mdu 2278 19 system system NN cord-014597-66vd2mdu 2278 20 . . . cord-014597-66vd2mdu 2279 1 Analysis analysis NN cord-014597-66vd2mdu 2279 2 of of IN cord-014597-66vd2mdu 2279 3 EGFR EGFR NNP cord-014597-66vd2mdu 2279 4 protein protein NN cord-014597-66vd2mdu 2279 5 yield yield NN cord-014597-66vd2mdu 2279 6 obtained obtain VBN cord-014597-66vd2mdu 2279 7 in in IN cord-014597-66vd2mdu 2279 8 a a DT cord-014597-66vd2mdu 2279 9 various various JJ cord-014597-66vd2mdu 2279 10 batches batch NNS cord-014597-66vd2mdu 2279 11 of of IN cord-014597-66vd2mdu 2279 12 CECF CECF NNP cord-014597-66vd2mdu 2279 13 formatted format VBN cord-014597-66vd2mdu 2279 14 reaction reaction NN cord-014597-66vd2mdu 2279 15 . . . cord-014597-66vd2mdu 2280 1 CECF CECF NNP cord-014597-66vd2mdu 2280 2 synthesis synthesis NN cord-014597-66vd2mdu 2280 3 was be VBD cord-014597-66vd2mdu 2280 4 performed perform VBN cord-014597-66vd2mdu 2280 5 in in IN cord-014597-66vd2mdu 2280 6 the the DT cord-014597-66vd2mdu 2280 7 presence presence NN cord-014597-66vd2mdu 2280 8 of of IN cord-014597-66vd2mdu 2280 9 14 14 CD cord-014597-66vd2mdu 2280 10 C c NN cord-014597-66vd2mdu 2280 11 leucine leucine NN cord-014597-66vd2mdu 2280 12 for for IN cord-014597-66vd2mdu 2280 13 radio radio NN cord-014597-66vd2mdu 2280 14 labeling labeling NN cord-014597-66vd2mdu 2280 15 of of IN cord-014597-66vd2mdu 2280 16 target target NN cord-014597-66vd2mdu 2280 17 proteins protein NNS cord-014597-66vd2mdu 2280 18 . . . cord-014597-66vd2mdu 2281 1 Radio radio NN cord-014597-66vd2mdu 2281 2 labeled label VBD cord-014597-66vd2mdu 2281 3 proteins protein NNS cord-014597-66vd2mdu 2281 4 were be VBD cord-014597-66vd2mdu 2281 5 precipitated precipitate VBN cord-014597-66vd2mdu 2281 6 using use VBG cord-014597-66vd2mdu 2281 7 TCA TCA NNP cord-014597-66vd2mdu 2281 8 followed follow VBN cord-014597-66vd2mdu 2281 9 by by IN cord-014597-66vd2mdu 2281 10 scintillation scintillation NN cord-014597-66vd2mdu 2281 11 measurement measurement NN cord-014597-66vd2mdu 2281 12 . . . cord-014597-66vd2mdu 2282 1 b b LS cord-014597-66vd2mdu 2282 2 Detection detection NN cord-014597-66vd2mdu 2282 3 of of IN cord-014597-66vd2mdu 2282 4 radio radio NN cord-014597-66vd2mdu 2282 5 labeled label VBN cord-014597-66vd2mdu 2282 6 EGFR EGFR NNP cord-014597-66vd2mdu 2282 7 by by IN cord-014597-66vd2mdu 2282 8 autoradiography autoradiography NNP cord-014597-66vd2mdu 2282 9 . . . cord-014597-66vd2mdu 2283 1 A a DT cord-014597-66vd2mdu 2283 2 no no DT cord-014597-66vd2mdu 2283 3 template template NN cord-014597-66vd2mdu 2283 4 control control NN cord-014597-66vd2mdu 2283 5 ( ( -LRB- cord-014597-66vd2mdu 2283 6 NTC NTC NNP cord-014597-66vd2mdu 2283 7 ) ) -RRB- cord-014597-66vd2mdu 2283 8 was be VBD cord-014597-66vd2mdu 2283 9 prepared prepare VBN cord-014597-66vd2mdu 2283 10 containing contain VBG cord-014597-66vd2mdu 2283 11 no no DT cord-014597-66vd2mdu 2283 12 EGFR EGFR NNP cord-014597-66vd2mdu 2283 13 DNA dna NN cord-014597-66vd2mdu 2283 14 template template NN cord-014597-66vd2mdu 2283 15 Background Background NNP cord-014597-66vd2mdu 2283 16 Emergence Emergence NNP cord-014597-66vd2mdu 2283 17 of of IN cord-014597-66vd2mdu 2283 18 stem stem NN cord-014597-66vd2mdu 2283 19 cell cell NN cord-014597-66vd2mdu 2283 20 - - HYPH cord-014597-66vd2mdu 2283 21 based base VBN cord-014597-66vd2mdu 2283 22 regenerative regenerative JJ cord-014597-66vd2mdu 2283 23 medicine medicine NN cord-014597-66vd2mdu 2283 24 recently recently RB cord-014597-66vd2mdu 2283 25 leaded lead VBD cord-014597-66vd2mdu 2283 26 to to IN cord-014597-66vd2mdu 2283 27 the the DT cord-014597-66vd2mdu 2283 28 necessity necessity NN cord-014597-66vd2mdu 2283 29 to to TO cord-014597-66vd2mdu 2283 30 reach reach VB cord-014597-66vd2mdu 2283 31 a a DT cord-014597-66vd2mdu 2283 32 sustained sustained JJ cord-014597-66vd2mdu 2283 33 production production NN cord-014597-66vd2mdu 2283 34 of of IN cord-014597-66vd2mdu 2283 35 such such JJ cord-014597-66vd2mdu 2283 36 cells cell NNS cord-014597-66vd2mdu 2283 37 [ [ -LRB- cord-014597-66vd2mdu 2283 38 1 1 CD cord-014597-66vd2mdu 2283 39 ] ] -RRB- cord-014597-66vd2mdu 2283 40 . . . cord-014597-66vd2mdu 2284 1 Hence hence RB cord-014597-66vd2mdu 2284 2 , , , cord-014597-66vd2mdu 2284 3 new new JJ cord-014597-66vd2mdu 2284 4 bioreactors bioreactor NNS cord-014597-66vd2mdu 2284 5 and and CC cord-014597-66vd2mdu 2284 6 carriers carrier NNS cord-014597-66vd2mdu 2284 7 were be VBD cord-014597-66vd2mdu 2284 8 designed design VBN cord-014597-66vd2mdu 2284 9 for for IN cord-014597-66vd2mdu 2284 10 cell cell NN cord-014597-66vd2mdu 2284 11 expansion expansion NN cord-014597-66vd2mdu 2284 12 . . . cord-014597-66vd2mdu 2285 1 However however RB cord-014597-66vd2mdu 2285 2 , , , cord-014597-66vd2mdu 2285 3 to to TO cord-014597-66vd2mdu 2285 4 meet meet VB cord-014597-66vd2mdu 2285 5 this this DT cord-014597-66vd2mdu 2285 6 increasing increase VBG cord-014597-66vd2mdu 2285 7 demand demand NN cord-014597-66vd2mdu 2285 8 , , , cord-014597-66vd2mdu 2285 9 improvement improvement NN cord-014597-66vd2mdu 2285 10 of of IN cord-014597-66vd2mdu 2285 11 both both CC cord-014597-66vd2mdu 2285 12 quality quality NN cord-014597-66vd2mdu 2285 13 and and CC cord-014597-66vd2mdu 2285 14 quantity quantity NN cord-014597-66vd2mdu 2285 15 of of IN cord-014597-66vd2mdu 2285 16 stem stem NN cord-014597-66vd2mdu 2285 17 cells cell NNS cord-014597-66vd2mdu 2285 18 remains remain VBZ cord-014597-66vd2mdu 2285 19 necessary necessary JJ cord-014597-66vd2mdu 2285 20 . . . cord-014597-66vd2mdu 2286 1 Soft soft JJ cord-014597-66vd2mdu 2286 2 biocompatible biocompatible JJ cord-014597-66vd2mdu 2286 3 microcarriers microcarrier NNS cord-014597-66vd2mdu 2286 4 mimicking mimic VBG cord-014597-66vd2mdu 2286 5 extracellular extracellular JJ cord-014597-66vd2mdu 2286 6 matrix matrix NN cord-014597-66vd2mdu 2286 7 in in IN cord-014597-66vd2mdu 2286 8 term term NN cord-014597-66vd2mdu 2286 9 of of IN cord-014597-66vd2mdu 2286 10 structure structure NN cord-014597-66vd2mdu 2286 11 and and CC cord-014597-66vd2mdu 2286 12 stiffness stiffness NN cord-014597-66vd2mdu 2286 13 should should MD cord-014597-66vd2mdu 2286 14 be be VB cord-014597-66vd2mdu 2286 15 of of IN cord-014597-66vd2mdu 2286 16 valuable valuable JJ cord-014597-66vd2mdu 2286 17 utility utility NN cord-014597-66vd2mdu 2286 18 as as IN cord-014597-66vd2mdu 2286 19 substrate substrate NN cord-014597-66vd2mdu 2286 20 stiffness stiffness NN cord-014597-66vd2mdu 2286 21 strongly strongly RB cord-014597-66vd2mdu 2286 22 influence influence VBP cord-014597-66vd2mdu 2286 23 in in IN cord-014597-66vd2mdu 2286 24 vitro vitro FW cord-014597-66vd2mdu 2286 25 stem stem NN cord-014597-66vd2mdu 2286 26 cell cell NN cord-014597-66vd2mdu 2286 27 fate fate NN cord-014597-66vd2mdu 2286 28 and and CC cord-014597-66vd2mdu 2286 29 differentiation differentiation NN cord-014597-66vd2mdu 2286 30 [ [ -LRB- cord-014597-66vd2mdu 2286 31 2 2 CD cord-014597-66vd2mdu 2286 32 , , , cord-014597-66vd2mdu 2286 33 3 3 CD cord-014597-66vd2mdu 2286 34 ] ] -RRB- cord-014597-66vd2mdu 2286 35 . . . cord-014597-66vd2mdu 2287 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2287 2 expertise expertise NN cord-014597-66vd2mdu 2287 3 in in IN cord-014597-66vd2mdu 2287 4 the the DT cord-014597-66vd2mdu 2287 5 field field NN cord-014597-66vd2mdu 2287 6 of of IN cord-014597-66vd2mdu 2287 7 microbeads microbead NNS cord-014597-66vd2mdu 2287 8 design design NN cord-014597-66vd2mdu 2287 9 using use VBG cord-014597-66vd2mdu 2287 10 jetcutting jetcutte VBG cord-014597-66vd2mdu 2287 11 technology technology NN cord-014597-66vd2mdu 2287 12 [ [ -LRB- cord-014597-66vd2mdu 2287 13 4 4 CD cord-014597-66vd2mdu 2287 14 ] ] -RRB- cord-014597-66vd2mdu 2287 15 enabled enable VBD cord-014597-66vd2mdu 2287 16 us -PRON- PRP cord-014597-66vd2mdu 2287 17 to to TO cord-014597-66vd2mdu 2287 18 engineer engineer VB cord-014597-66vd2mdu 2287 19 + + CC cord-014597-66vd2mdu 2287 20 /-200 /-200 . cord-014597-66vd2mdu 2287 21 μm μm NN cord-014597-66vd2mdu 2287 22 alginate alginate NN cord-014597-66vd2mdu 2287 23 beads bead NNS cord-014597-66vd2mdu 2287 24 of of IN cord-014597-66vd2mdu 2287 25 various various JJ cord-014597-66vd2mdu 2287 26 G g NN cord-014597-66vd2mdu 2287 27 / / SYM cord-014597-66vd2mdu 2287 28 M M NNP cord-014597-66vd2mdu 2287 29 monomer monomer NN cord-014597-66vd2mdu 2287 30 ratio ratio NN cord-014597-66vd2mdu 2287 31 . . . cord-014597-66vd2mdu 2288 1 We -PRON- PRP cord-014597-66vd2mdu 2288 2 used use VBD cord-014597-66vd2mdu 2288 3 jetcutter jetcutter NNP cord-014597-66vd2mdu 2288 4 ( ( -LRB- cord-014597-66vd2mdu 2288 5 geniaLab geniaLab NNP cord-014597-66vd2mdu 2288 6 Gmbh Gmbh NNP cord-014597-66vd2mdu 2288 7 ) ) -RRB- cord-014597-66vd2mdu 2288 8 with with IN cord-014597-66vd2mdu 2288 9 100 100 CD cord-014597-66vd2mdu 2288 10 μm μm NN cord-014597-66vd2mdu 2288 11 nozzle nozzle NN cord-014597-66vd2mdu 2288 12 at at IN cord-014597-66vd2mdu 2288 13 max max NN cord-014597-66vd2mdu 2288 14 speed speed NN cord-014597-66vd2mdu 2288 15 12000 12000 CD cord-014597-66vd2mdu 2288 16 rpm rpm NN cord-014597-66vd2mdu 2288 17 . . . cord-014597-66vd2mdu 2289 1 Alginate alginate NN cord-014597-66vd2mdu 2289 2 solutions solution NNS cord-014597-66vd2mdu 2289 3 with with IN cord-014597-66vd2mdu 2289 4 concentrations concentration NNS cord-014597-66vd2mdu 2289 5 2 2 CD cord-014597-66vd2mdu 2289 6 % % NN cord-014597-66vd2mdu 2289 7 to to TO cord-014597-66vd2mdu 2289 8 4 4 CD cord-014597-66vd2mdu 2289 9 % % NN cord-014597-66vd2mdu 2289 10 were be VBD cord-014597-66vd2mdu 2289 11 gelifyed gelifye VBN cord-014597-66vd2mdu 2289 12 in in IN cord-014597-66vd2mdu 2289 13 2 2 CD cord-014597-66vd2mdu 2289 14 % % NN cord-014597-66vd2mdu 2289 15 CaCl2 cacl2 NN cord-014597-66vd2mdu 2289 16 EtOH EtOH NNP cord-014597-66vd2mdu 2289 17 50 50 CD cord-014597-66vd2mdu 2289 18 % % NN cord-014597-66vd2mdu 2289 19 solution solution NN cord-014597-66vd2mdu 2289 20 . . . cord-014597-66vd2mdu 2290 1 Alginates Alginates NNP cord-014597-66vd2mdu 2290 2 with with IN cord-014597-66vd2mdu 2290 3 estimated estimate VBN cord-014597-66vd2mdu 2290 4 viscosity viscosity NN cord-014597-66vd2mdu 2290 5 ( ( -LRB- cord-014597-66vd2mdu 2290 6 @1 @1 : cord-014597-66vd2mdu 2290 7 % % NN cord-014597-66vd2mdu 2290 8 ) ) -RRB- cord-014597-66vd2mdu 2290 9 from from IN cord-014597-66vd2mdu 2290 10 30 30 CD cord-014597-66vd2mdu 2290 11 to to IN cord-014597-66vd2mdu 2290 12 720 720 CD cord-014597-66vd2mdu 2290 13 mPa mPa NNS cord-014597-66vd2mdu 2290 14 were be VBD cord-014597-66vd2mdu 2290 15 tested test VBN cord-014597-66vd2mdu 2290 16 . . . cord-014597-66vd2mdu 2291 1 A a DT cord-014597-66vd2mdu 2291 2 further further JJ cord-014597-66vd2mdu 2291 3 surface surface NN cord-014597-66vd2mdu 2291 4 treatment treatment NN cord-014597-66vd2mdu 2291 5 with with IN cord-014597-66vd2mdu 2291 6 gelatine gelatine NN cord-014597-66vd2mdu 2291 7 ( ( -LRB- cord-014597-66vd2mdu 2291 8 0,1 0,1 CD cord-014597-66vd2mdu 2291 9 % % NN cord-014597-66vd2mdu 2291 10 , , , cord-014597-66vd2mdu 2291 11 1 1 CD cord-014597-66vd2mdu 2291 12 % % NN cord-014597-66vd2mdu 2291 13 ) ) -RRB- cord-014597-66vd2mdu 2291 14 and and CC cord-014597-66vd2mdu 2291 15 poly poly NNP cord-014597-66vd2mdu 2291 16 - - HYPH cord-014597-66vd2mdu 2291 17 L l NN cord-014597-66vd2mdu 2291 18 - - HYPH cord-014597-66vd2mdu 2291 19 lysine lysine NN cord-014597-66vd2mdu 2291 20 ( ( -LRB- cord-014597-66vd2mdu 2291 21 0,1 0,1 CD cord-014597-66vd2mdu 2291 22 % % NN cord-014597-66vd2mdu 2291 23 ) ) -RRB- cord-014597-66vd2mdu 2291 24 was be VBD cord-014597-66vd2mdu 2291 25 carried carry VBN cord-014597-66vd2mdu 2291 26 out out RP cord-014597-66vd2mdu 2291 27 to to TO cord-014597-66vd2mdu 2291 28 reach reach VB cord-014597-66vd2mdu 2291 29 an an DT cord-014597-66vd2mdu 2291 30 optimal optimal JJ cord-014597-66vd2mdu 2291 31 cell cell NN cord-014597-66vd2mdu 2291 32 anchoring anchoring NN cord-014597-66vd2mdu 2291 33 of of IN cord-014597-66vd2mdu 2291 34 human human JJ cord-014597-66vd2mdu 2291 35 adiposederived adiposederive VBN cord-014597-66vd2mdu 2291 36 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2291 37 stem stem NN cord-014597-66vd2mdu 2291 38 cells cell NNS cord-014597-66vd2mdu 2291 39 ( ( -LRB- cord-014597-66vd2mdu 2291 40 ATCC ATCC NNP cord-014597-66vd2mdu 2291 41 - - HYPH cord-014597-66vd2mdu 2291 42 PSC-500 PSC-500 NNP cord-014597-66vd2mdu 2291 43 - - HYPH cord-014597-66vd2mdu 2291 44 011 011 CD cord-014597-66vd2mdu 2291 45 ) ) -RRB- cord-014597-66vd2mdu 2291 46 in in IN cord-014597-66vd2mdu 2291 47 MesemPro MesemPro NNP cord-014597-66vd2mdu 2291 48 RS rs NN cord-014597-66vd2mdu 2291 49 medium medium NN cord-014597-66vd2mdu 2291 50 ( ( -LRB- cord-014597-66vd2mdu 2291 51 Gibco Gibco NNP cord-014597-66vd2mdu 2291 52 ) ) -RRB- cord-014597-66vd2mdu 2291 53 . . . cord-014597-66vd2mdu 2292 1 Jetcutter Jetcutter NNP cord-014597-66vd2mdu 2292 2 technology technology NN cord-014597-66vd2mdu 2292 3 allowed allow VBD cord-014597-66vd2mdu 2292 4 us -PRON- PRP cord-014597-66vd2mdu 2292 5 to to TO cord-014597-66vd2mdu 2292 6 obtain obtain VB cord-014597-66vd2mdu 2292 7 alginate alginate NN cord-014597-66vd2mdu 2292 8 microcarriers microcarrier NNS cord-014597-66vd2mdu 2292 9 with with IN cord-014597-66vd2mdu 2292 10 a a DT cord-014597-66vd2mdu 2292 11 good good JJ cord-014597-66vd2mdu 2292 12 homogeneity homogeneity NN cord-014597-66vd2mdu 2292 13 in in IN cord-014597-66vd2mdu 2292 14 size size NN cord-014597-66vd2mdu 2292 15 around around IN cord-014597-66vd2mdu 2292 16 200 200 CD cord-014597-66vd2mdu 2292 17 μm μm NNS cord-014597-66vd2mdu 2292 18 and and CC cord-014597-66vd2mdu 2292 19 sphericity sphericity NN cord-014597-66vd2mdu 2292 20 comparable comparable JJ cord-014597-66vd2mdu 2292 21 to to IN cord-014597-66vd2mdu 2292 22 commercial commercial JJ cord-014597-66vd2mdu 2292 23 carriers carrier NNS cord-014597-66vd2mdu 2292 24 ( ( -LRB- cord-014597-66vd2mdu 2292 25 Table table NN cord-014597-66vd2mdu 2292 26 1 1 CD cord-014597-66vd2mdu 2292 27 ) ) -RRB- cord-014597-66vd2mdu 2292 28 . . . cord-014597-66vd2mdu 2293 1 Best good JJS cord-014597-66vd2mdu 2293 2 adhesion adhesion NN cord-014597-66vd2mdu 2293 3 of of IN cord-014597-66vd2mdu 2293 4 human human JJ cord-014597-66vd2mdu 2293 5 adipose adipose NN cord-014597-66vd2mdu 2293 6 - - HYPH cord-014597-66vd2mdu 2293 7 derived derive VBN cord-014597-66vd2mdu 2293 8 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2293 9 stem stem NN cord-014597-66vd2mdu 2293 10 cells cell NNS cord-014597-66vd2mdu 2293 11 was be VBD cord-014597-66vd2mdu 2293 12 obtained obtain VBN cord-014597-66vd2mdu 2293 13 on on IN cord-014597-66vd2mdu 2293 14 0,1 0,1 CD cord-014597-66vd2mdu 2293 15 % % NN cord-014597-66vd2mdu 2293 16 gelatine gelatine NN cord-014597-66vd2mdu 2293 17 coated coat VBN cord-014597-66vd2mdu 2293 18 alginate alginate NN cord-014597-66vd2mdu 2293 19 carriers carrier NNS cord-014597-66vd2mdu 2293 20 ( ( -LRB- cord-014597-66vd2mdu 2293 21 Fig fig NN cord-014597-66vd2mdu 2293 22 . . NNP cord-014597-66vd2mdu 2293 23 1 1 CD cord-014597-66vd2mdu 2293 24 ) ) -RRB- cord-014597-66vd2mdu 2293 25 . . . cord-014597-66vd2mdu 2294 1 We -PRON- PRP cord-014597-66vd2mdu 2294 2 observed observe VBD cord-014597-66vd2mdu 2294 3 limited limited JJ cord-014597-66vd2mdu 2294 4 apoptosis apoptosis NN cord-014597-66vd2mdu 2294 5 and and CC cord-014597-66vd2mdu 2294 6 human human JJ cord-014597-66vd2mdu 2294 7 adipose adipose NN cord-014597-66vd2mdu 2294 8 - - HYPH cord-014597-66vd2mdu 2294 9 derived derive VBN cord-014597-66vd2mdu 2294 10 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2294 11 cells cell NNS cord-014597-66vd2mdu 2294 12 stemness stemness JJ cord-014597-66vd2mdu 2294 13 was be VBD cord-014597-66vd2mdu 2294 14 conserved conserve VBN cord-014597-66vd2mdu 2294 15 after after IN cord-014597-66vd2mdu 2294 16 14 14 CD cord-014597-66vd2mdu 2294 17 days day NNS cord-014597-66vd2mdu 2294 18 in in IN cord-014597-66vd2mdu 2294 19 culture culture NN cord-014597-66vd2mdu 2294 20 ( ( -LRB- cord-014597-66vd2mdu 2294 21 data datum NNS cord-014597-66vd2mdu 2294 22 not not RB cord-014597-66vd2mdu 2294 23 shown show VBN cord-014597-66vd2mdu 2294 24 ) ) -RRB- cord-014597-66vd2mdu 2294 25 . . . cord-014597-66vd2mdu 2295 1 Cellular cellular JJ cord-014597-66vd2mdu 2295 2 bioassays bioassay NNS cord-014597-66vd2mdu 2295 3 developed develop VBD cord-014597-66vd2mdu 2295 4 with with IN cord-014597-66vd2mdu 2295 5 functionally functionally RB cord-014597-66vd2mdu 2295 6 immortalized immortalize VBN cord-014597-66vd2mdu 2295 7 cell cell NN cord-014597-66vd2mdu 2295 8 lines line NNS cord-014597-66vd2mdu 2295 9 Aileen Aileen NNP cord-014597-66vd2mdu 2295 10 Bleisch Bleisch NNP cord-014597-66vd2mdu 2295 11 1 1 CD cord-014597-66vd2mdu 2295 12 , , , cord-014597-66vd2mdu 2295 13 Aleksandra Aleksandra NNP cord-014597-66vd2mdu 2295 14 Velkova Velkova NNP cord-014597-66vd2mdu 2295 15 3 3 CD cord-014597-66vd2mdu 2295 16 , , , cord-014597-66vd2mdu 2295 17 Tom Tom NNP cord-014597-66vd2mdu 2295 18 Wahlicht Wahlicht NNP cord-014597-66vd2mdu 2295 19 2 2 CD cord-014597-66vd2mdu 2295 20 , , , cord-014597-66vd2mdu 2295 21 Dagmar Dagmar NNP cord-014597-66vd2mdu 2295 22 Wirth Wirth NNP cord-014597-66vd2mdu 2295 23 2 2 CD cord-014597-66vd2mdu 2295 24 , , , cord-014597-66vd2mdu 2295 25 Tobias Tobias NNP cord-014597-66vd2mdu 2295 26 May May NNP cord-014597-66vd2mdu 2295 27 1 1 CD cord-014597-66vd2mdu 2295 28 1 1 CD cord-014597-66vd2mdu 2295 29 InSCREENeX inscreenex NN cord-014597-66vd2mdu 2295 30 GmbH GmbH NNP cord-014597-66vd2mdu 2295 31 , , , cord-014597-66vd2mdu 2295 32 Braunschweig Braunschweig NNP cord-014597-66vd2mdu 2295 33 , , , cord-014597-66vd2mdu 2295 34 Germany Germany NNP cord-014597-66vd2mdu 2295 35 ; ; : cord-014597-66vd2mdu 2295 36 2 2 CD cord-014597-66vd2mdu 2295 37 MSYS MSYS NNP cord-014597-66vd2mdu 2295 38 , , , cord-014597-66vd2mdu 2295 39 Helmholtz Helmholtz NNP cord-014597-66vd2mdu 2295 40 Centre Centre NNP cord-014597-66vd2mdu 2295 41 for for IN cord-014597-66vd2mdu 2295 42 Infection Infection NNP cord-014597-66vd2mdu 2295 43 Research Research NNP cord-014597-66vd2mdu 2295 44 , , , cord-014597-66vd2mdu 2295 45 Braunschweig Braunschweig NNP cord-014597-66vd2mdu 2295 46 , , , cord-014597-66vd2mdu 2295 47 Germany Germany NNP cord-014597-66vd2mdu 2295 48 ; ; : cord-014597-66vd2mdu 2295 49 3 3 CD cord-014597-66vd2mdu 2295 50 Greiner Greiner NNP cord-014597-66vd2mdu 2295 51 Bio Bio NNP cord-014597-66vd2mdu 2295 52 - - HYPH cord-014597-66vd2mdu 2295 53 One one CD cord-014597-66vd2mdu 2295 54 GmbH GmbH NNP cord-014597-66vd2mdu 2295 55 , , , cord-014597-66vd2mdu 2295 56 Frickenhausen Frickenhausen NNP cord-014597-66vd2mdu 2295 57 , , , cord-014597-66vd2mdu 2295 58 Germany Germany NNP cord-014597-66vd2mdu 2295 59 BMC BMC NNP cord-014597-66vd2mdu 2295 60 Proceedings Proceedings NNP cord-014597-66vd2mdu 2295 61 2018 2018 CD cord-014597-66vd2mdu 2295 62 , , , cord-014597-66vd2mdu 2296 1 12(Suppl 12(suppl CD cord-014597-66vd2mdu 2296 2 1):P-381 1):p-381 CD cord-014597-66vd2mdu 2297 1 Background background VB cord-014597-66vd2mdu 2297 2 A a DT cord-014597-66vd2mdu 2297 3 major major JJ cord-014597-66vd2mdu 2297 4 challenge challenge NN cord-014597-66vd2mdu 2297 5 of of IN cord-014597-66vd2mdu 2297 6 current current JJ cord-014597-66vd2mdu 2297 7 research research NN cord-014597-66vd2mdu 2297 8 is be VBZ cord-014597-66vd2mdu 2297 9 the the DT cord-014597-66vd2mdu 2297 10 limited limited JJ cord-014597-66vd2mdu 2297 11 availability availability NN cord-014597-66vd2mdu 2297 12 of of IN cord-014597-66vd2mdu 2297 13 physiologically physiologically RB cord-014597-66vd2mdu 2297 14 relevant relevant JJ cord-014597-66vd2mdu 2297 15 cells cell NNS cord-014597-66vd2mdu 2297 16 [ [ -LRB- cord-014597-66vd2mdu 2297 17 1 1 CD cord-014597-66vd2mdu 2297 18 ] ] -RRB- cord-014597-66vd2mdu 2297 19 . . . cord-014597-66vd2mdu 2298 1 Thus thus RB cord-014597-66vd2mdu 2298 2 the the DT cord-014597-66vd2mdu 2298 3 development development NN cord-014597-66vd2mdu 2298 4 of of IN cord-014597-66vd2mdu 2298 5 relevant relevant JJ cord-014597-66vd2mdu 2298 6 cellular cellular JJ cord-014597-66vd2mdu 2298 7 bioassays bioassay NNS cord-014597-66vd2mdu 2298 8 that that WDT cord-014597-66vd2mdu 2298 9 are be VBP cord-014597-66vd2mdu 2298 10 robust robust JJ cord-014597-66vd2mdu 2298 11 , , , cord-014597-66vd2mdu 2298 12 reproducible reproducible JJ cord-014597-66vd2mdu 2298 13 and and CC cord-014597-66vd2mdu 2298 14 scalable scalable JJ cord-014597-66vd2mdu 2298 15 is be VBZ cord-014597-66vd2mdu 2298 16 hindered hinder VBN cord-014597-66vd2mdu 2298 17 . . . cord-014597-66vd2mdu 2299 1 To to TO cord-014597-66vd2mdu 2299 2 overcome overcome VB cord-014597-66vd2mdu 2299 3 current current JJ cord-014597-66vd2mdu 2299 4 limitations limitation NNS cord-014597-66vd2mdu 2299 5 we -PRON- PRP cord-014597-66vd2mdu 2299 6 developed develop VBD cord-014597-66vd2mdu 2299 7 an an DT cord-014597-66vd2mdu 2299 8 immortalization immortalization NN cord-014597-66vd2mdu 2299 9 strategy strategy NN cord-014597-66vd2mdu 2299 10 allowing allow VBG cord-014597-66vd2mdu 2299 11 the the DT cord-014597-66vd2mdu 2299 12 efficient efficient JJ cord-014597-66vd2mdu 2299 13 and and CC cord-014597-66vd2mdu 2299 14 reproducible reproducible JJ cord-014597-66vd2mdu 2299 15 establishment establishment NN cord-014597-66vd2mdu 2299 16 of of IN cord-014597-66vd2mdu 2299 17 novel novel JJ cord-014597-66vd2mdu 2299 18 cell cell NN cord-014597-66vd2mdu 2299 19 lines line NNS cord-014597-66vd2mdu 2299 20 showing show VBG cord-014597-66vd2mdu 2299 21 an an DT cord-014597-66vd2mdu 2299 22 in in IN cord-014597-66vd2mdu 2299 23 vivo vivo NN cord-014597-66vd2mdu 2299 24 - - HYPH cord-014597-66vd2mdu 2299 25 like like JJ cord-014597-66vd2mdu 2299 26 phenotype phenotype NN cord-014597-66vd2mdu 2299 27 . . . cord-014597-66vd2mdu 2300 1 The the DT cord-014597-66vd2mdu 2300 2 main main JJ cord-014597-66vd2mdu 2300 3 feature feature NN cord-014597-66vd2mdu 2300 4 of of IN cord-014597-66vd2mdu 2300 5 our -PRON- PRP$ cord-014597-66vd2mdu 2300 6 CI ci NN cord-014597-66vd2mdu 2300 7 - - HYPH cord-014597-66vd2mdu 2300 8 SCREEN screen NN cord-014597-66vd2mdu 2300 9 technology technology NN cord-014597-66vd2mdu 2300 10 is be VBZ cord-014597-66vd2mdu 2300 11 the the DT cord-014597-66vd2mdu 2300 12 ability ability NN cord-014597-66vd2mdu 2300 13 to to TO cord-014597-66vd2mdu 2300 14 combine combine VB cord-014597-66vd2mdu 2300 15 the the DT cord-014597-66vd2mdu 2300 16 advantage advantage NN cord-014597-66vd2mdu 2300 17 of of IN cord-014597-66vd2mdu 2300 18 cell cell NN cord-014597-66vd2mdu 2300 19 linesthe linesthe DT cord-014597-66vd2mdu 2300 20 unlimited unlimited JJ cord-014597-66vd2mdu 2300 21 cell cell NN cord-014597-66vd2mdu 2300 22 supplywith supplywith NN cord-014597-66vd2mdu 2300 23 the the DT cord-014597-66vd2mdu 2300 24 advantage advantage NN cord-014597-66vd2mdu 2300 25 of of IN cord-014597-66vd2mdu 2300 26 primary primary JJ cord-014597-66vd2mdu 2300 27 cellsthe cellsthe DT cord-014597-66vd2mdu 2300 28 physiological physiological JJ cord-014597-66vd2mdu 2300 29 relevance relevance NN cord-014597-66vd2mdu 2300 30 . . . cord-014597-66vd2mdu 2301 1 Using use VBG cord-014597-66vd2mdu 2301 2 this this DT cord-014597-66vd2mdu 2301 3 technology technology NN cord-014597-66vd2mdu 2301 4 we -PRON- PRP cord-014597-66vd2mdu 2301 5 have have VBP cord-014597-66vd2mdu 2301 6 immortalized immortalize VBN cord-014597-66vd2mdu 2301 7 , , , cord-014597-66vd2mdu 2301 8 amongst amongst IN cord-014597-66vd2mdu 2301 9 others other NNS cord-014597-66vd2mdu 2301 10 , , , cord-014597-66vd2mdu 2301 11 a a DT cord-014597-66vd2mdu 2301 12 human human JJ cord-014597-66vd2mdu 2301 13 osteoblast osteoblast JJ cord-014597-66vd2mdu 2301 14 cell cell NN cord-014597-66vd2mdu 2301 15 line line NN cord-014597-66vd2mdu 2301 16 ( ( -LRB- cord-014597-66vd2mdu 2301 17 CI CI NNP cord-014597-66vd2mdu 2301 18 - - HYPH cord-014597-66vd2mdu 2301 19 huOB huOB NNP cord-014597-66vd2mdu 2301 20 ) ) -RRB- cord-014597-66vd2mdu 2301 21 [ [ -LRB- cord-014597-66vd2mdu 2301 22 2 2 CD cord-014597-66vd2mdu 2301 23 ] ] -RRB- cord-014597-66vd2mdu 2301 24 . . . cord-014597-66vd2mdu 2302 1 In in IN cord-014597-66vd2mdu 2302 2 the the DT cord-014597-66vd2mdu 2302 3 present present JJ cord-014597-66vd2mdu 2302 4 study study NN cord-014597-66vd2mdu 2302 5 , , , cord-014597-66vd2mdu 2302 6 the the DT cord-014597-66vd2mdu 2302 7 in in IN cord-014597-66vd2mdu 2302 8 vivo vivo NN cord-014597-66vd2mdu 2302 9 - - HYPH cord-014597-66vd2mdu 2302 10 like like JJ cord-014597-66vd2mdu 2302 11 phenotype phenotype NN cord-014597-66vd2mdu 2302 12 and and CC cord-014597-66vd2mdu 2302 13 functionality functionality NN cord-014597-66vd2mdu 2302 14 of of IN cord-014597-66vd2mdu 2302 15 the the DT cord-014597-66vd2mdu 2302 16 novel novel JJ cord-014597-66vd2mdu 2302 17 CI CI NNP cord-014597-66vd2mdu 2302 18 - - HYPH cord-014597-66vd2mdu 2302 19 huOB huOB NNP cord-014597-66vd2mdu 2302 20 was be VBD cord-014597-66vd2mdu 2302 21 examined examine VBN cord-014597-66vd2mdu 2302 22 . . . cord-014597-66vd2mdu 2303 1 Therefore therefore RB cord-014597-66vd2mdu 2303 2 , , , cord-014597-66vd2mdu 2303 3 CI CI NNP cord-014597-66vd2mdu 2303 4 - - HYPH cord-014597-66vd2mdu 2303 5 huOB huOB NNP cord-014597-66vd2mdu 2303 6 cells cell NNS cord-014597-66vd2mdu 2303 7 were be VBD cord-014597-66vd2mdu 2303 8 used use VBN cord-014597-66vd2mdu 2303 9 to to TO cord-014597-66vd2mdu 2303 10 develop develop VB cord-014597-66vd2mdu 2303 11 a a DT cord-014597-66vd2mdu 2303 12 3D 3d JJ cord-014597-66vd2mdu 2303 13 cell cell NN cord-014597-66vd2mdu 2303 14 culture culture NN cord-014597-66vd2mdu 2303 15 model model NN cord-014597-66vd2mdu 2303 16 by by IN cord-014597-66vd2mdu 2303 17 using use VBG cord-014597-66vd2mdu 2303 18 the the DT cord-014597-66vd2mdu 2303 19 magnetic magnetic JJ cord-014597-66vd2mdu 2303 20 3D 3D NNP cord-014597-66vd2mdu 2303 21 bioprinting bioprinting NNP cord-014597-66vd2mdu 2303 22 technology technology NNP cord-014597-66vd2mdu 2303 23 ( ( -LRB- cord-014597-66vd2mdu 2303 24 Nano3D Nano3D NNP cord-014597-66vd2mdu 2303 25 Biosciences Biosciences NNP cord-014597-66vd2mdu 2303 26 , , , cord-014597-66vd2mdu 2303 27 Houston Houston NNP cord-014597-66vd2mdu 2303 28 , , , cord-014597-66vd2mdu 2303 29 TX TX NNP cord-014597-66vd2mdu 2303 30 , , , cord-014597-66vd2mdu 2303 31 USA USA NNP cord-014597-66vd2mdu 2303 32 ) ) -RRB- cord-014597-66vd2mdu 2303 33 [ [ -LRB- cord-014597-66vd2mdu 2303 34 3 3 CD cord-014597-66vd2mdu 2303 35 ] ] -RRB- cord-014597-66vd2mdu 2303 36 . . . cord-014597-66vd2mdu 2304 1 The the DT cord-014597-66vd2mdu 2304 2 CI CI NNP cord-014597-66vd2mdu 2304 3 - - HYPH cord-014597-66vd2mdu 2304 4 huOB huOB NNP cord-014597-66vd2mdu 2304 5 cell cell NN cord-014597-66vd2mdu 2304 6 line line NN cord-014597-66vd2mdu 2304 7 was be VBD cord-014597-66vd2mdu 2304 8 recently recently RB cord-014597-66vd2mdu 2304 9 described describe VBN cord-014597-66vd2mdu 2304 10 and and CC cord-014597-66vd2mdu 2304 11 cultivated cultivate VBN cord-014597-66vd2mdu 2304 12 in in IN cord-014597-66vd2mdu 2304 13 huOB huOB NNP cord-014597-66vd2mdu 2304 14 Maintenance Maintenance NNP cord-014597-66vd2mdu 2304 15 Medium medium NN cord-014597-66vd2mdu 2304 16 ( ( -LRB- cord-014597-66vd2mdu 2304 17 InSCREENeX inscreenex NN cord-014597-66vd2mdu 2304 18 , , , cord-014597-66vd2mdu 2304 19 Germany Germany NNP cord-014597-66vd2mdu 2304 20 ) ) -RRB- cord-014597-66vd2mdu 2304 21 . . . cord-014597-66vd2mdu 2305 1 For for IN cord-014597-66vd2mdu 2305 2 spheroid spheroid NN cord-014597-66vd2mdu 2305 3 creation creation NN cord-014597-66vd2mdu 2305 4 CI CI NNP cord-014597-66vd2mdu 2305 5 - - HYPH cord-014597-66vd2mdu 2305 6 huOBs huOBs NNP cord-014597-66vd2mdu 2305 7 were be VBD cord-014597-66vd2mdu 2305 8 grown grow VBN cord-014597-66vd2mdu 2305 9 in in IN cord-014597-66vd2mdu 2305 10 a a DT cord-014597-66vd2mdu 2305 11 monolayer monolayer NN cord-014597-66vd2mdu 2305 12 , , , cord-014597-66vd2mdu 2305 13 magnetized magnetize VBN cord-014597-66vd2mdu 2305 14 by by IN cord-014597-66vd2mdu 2305 15 adding add VBG cord-014597-66vd2mdu 2305 16 a a DT cord-014597-66vd2mdu 2305 17 magnetic magnetic JJ cord-014597-66vd2mdu 2305 18 nanoparticle nanoparticle NN cord-014597-66vd2mdu 2305 19 assembly assembly NN cord-014597-66vd2mdu 2305 20 ( ( -LRB- cord-014597-66vd2mdu 2305 21 NanoShuttle NanoShuttle NNP cord-014597-66vd2mdu 2305 22 , , , cord-014597-66vd2mdu 2305 23 NS NS NNP cord-014597-66vd2mdu 2305 24 , , , cord-014597-66vd2mdu 2305 25 Nano3D Nano3D NNP cord-014597-66vd2mdu 2305 26 Biosciences Biosciences NNP cord-014597-66vd2mdu 2305 27 , , , cord-014597-66vd2mdu 2305 28 Houston Houston NNP cord-014597-66vd2mdu 2305 29 , , , cord-014597-66vd2mdu 2305 30 TX TX NNP cord-014597-66vd2mdu 2305 31 , , , cord-014597-66vd2mdu 2305 32 USA USA NNP cord-014597-66vd2mdu 2305 33 ) ) -RRB- cord-014597-66vd2mdu 2305 34 at at IN cord-014597-66vd2mdu 2305 35 a a DT cord-014597-66vd2mdu 2305 36 concentration concentration NN cord-014597-66vd2mdu 2305 37 of of IN cord-014597-66vd2mdu 2305 38 4μl 4μl JJ cord-014597-66vd2mdu 2305 39 NS NS NNP cord-014597-66vd2mdu 2305 40 / / SYM cord-014597-66vd2mdu 2305 41 cm cm NNP cord-014597-66vd2mdu 2305 42 2 2 CD cord-014597-66vd2mdu 2305 43 growth growth NN cord-014597-66vd2mdu 2305 44 area area NN cord-014597-66vd2mdu 2305 45 . . . cord-014597-66vd2mdu 2306 1 After after IN cord-014597-66vd2mdu 2306 2 an an DT cord-014597-66vd2mdu 2306 3 overnight overnight JJ cord-014597-66vd2mdu 2306 4 incubation incubation NN cord-014597-66vd2mdu 2306 5 magnetized magnetize VBD cord-014597-66vd2mdu 2306 6 CI CI NNP cord-014597-66vd2mdu 2306 7 - - HYPH cord-014597-66vd2mdu 2306 8 huOB huOB NNP cord-014597-66vd2mdu 2306 9 were be VBD cord-014597-66vd2mdu 2306 10 detached detach VBN cord-014597-66vd2mdu 2306 11 and and CC cord-014597-66vd2mdu 2306 12 seeded seed VBN cord-014597-66vd2mdu 2306 13 into into IN cord-014597-66vd2mdu 2306 14 Cellstar Cellstar NNP cord-014597-66vd2mdu 2306 15 ® ® . cord-014597-66vd2mdu 2306 16 Cell cell NN cord-014597-66vd2mdu 2306 17 - - HYPH cord-014597-66vd2mdu 2306 18 Repellent Repellent NNP cord-014597-66vd2mdu 2306 19 96-well 96-well CD cord-014597-66vd2mdu 2306 20 plates plate NNS cord-014597-66vd2mdu 2307 1 ( ( -LRB- cord-014597-66vd2mdu 2307 2 Greiner Greiner NNP cord-014597-66vd2mdu 2307 3 Bio Bio NNP cord-014597-66vd2mdu 2307 4 - - HYPH cord-014597-66vd2mdu 2307 5 One One NNP cord-014597-66vd2mdu 2307 6 , , , cord-014597-66vd2mdu 2307 7 Frickenhausen Frickenhausen NNP cord-014597-66vd2mdu 2307 8 , , , cord-014597-66vd2mdu 2307 9 Germany Germany NNP cord-014597-66vd2mdu 2307 10 ) ) -RRB- cord-014597-66vd2mdu 2307 11 . . . cord-014597-66vd2mdu 2308 1 With with IN cord-014597-66vd2mdu 2308 2 the the DT cord-014597-66vd2mdu 2308 3 help help NN cord-014597-66vd2mdu 2308 4 of of IN cord-014597-66vd2mdu 2308 5 mild mild JJ cord-014597-66vd2mdu 2308 6 magnetic magnetic JJ cord-014597-66vd2mdu 2308 7 forces force NNS cord-014597-66vd2mdu 2308 8 cells cell NNS cord-014597-66vd2mdu 2308 9 were be VBD cord-014597-66vd2mdu 2308 10 printed print VBN cord-014597-66vd2mdu 2308 11 into into IN cord-014597-66vd2mdu 2308 12 spheroids spheroid NNS cord-014597-66vd2mdu 2308 13 within within IN cord-014597-66vd2mdu 2308 14 2h 2h CD cord-014597-66vd2mdu 2308 15 . . . cord-014597-66vd2mdu 2309 1 These these DT cord-014597-66vd2mdu 2309 2 consist consist VBP cord-014597-66vd2mdu 2309 3 of of IN cord-014597-66vd2mdu 2309 4 1.000 1.000 CD cord-014597-66vd2mdu 2309 5 - - SYM cord-014597-66vd2mdu 2309 6 50.000 50.000 CD cord-014597-66vd2mdu 2309 7 cells cell NNS cord-014597-66vd2mdu 2309 8 and and CC cord-014597-66vd2mdu 2309 9 were be VBD cord-014597-66vd2mdu 2309 10 cultured culture VBN cord-014597-66vd2mdu 2309 11 for for IN cord-014597-66vd2mdu 2309 12 a a DT cord-014597-66vd2mdu 2309 13 period period NN cord-014597-66vd2mdu 2309 14 of of IN cord-014597-66vd2mdu 2309 15 up up IN cord-014597-66vd2mdu 2309 16 to to TO cord-014597-66vd2mdu 2309 17 50 50 CD cord-014597-66vd2mdu 2309 18 days day NNS cord-014597-66vd2mdu 2309 19 . . . cord-014597-66vd2mdu 2310 1 The the DT cord-014597-66vd2mdu 2310 2 cell cell NN cord-014597-66vd2mdu 2310 3 viability viability NN cord-014597-66vd2mdu 2310 4 was be VBD cord-014597-66vd2mdu 2310 5 analyzed analyze VBN cord-014597-66vd2mdu 2310 6 by by IN cord-014597-66vd2mdu 2310 7 a a DT cord-014597-66vd2mdu 2310 8 Propidium Propidium NNP cord-014597-66vd2mdu 2310 9 iodide iodide NN cord-014597-66vd2mdu 2310 10 ( ( -LRB- cord-014597-66vd2mdu 2310 11 PI PI NNP cord-014597-66vd2mdu 2310 12 ) ) -RRB- cord-014597-66vd2mdu 2310 13 and and CC cord-014597-66vd2mdu 2310 14 Calcein Calcein NNP cord-014597-66vd2mdu 2310 15 AM am VBP cord-014597-66vd2mdu 2310 16 staining stain VBG cord-014597-66vd2mdu 2310 17 . . . cord-014597-66vd2mdu 2311 1 To to TO cord-014597-66vd2mdu 2311 2 improve improve VB cord-014597-66vd2mdu 2311 3 spheroid spheroid NN cord-014597-66vd2mdu 2311 4 functionality functionality NN cord-014597-66vd2mdu 2311 5 spheroids spheroid NNS cord-014597-66vd2mdu 2311 6 were be VBD cord-014597-66vd2mdu 2311 7 cultivated cultivate VBN cord-014597-66vd2mdu 2311 8 with with IN cord-014597-66vd2mdu 2311 9 huOB huOB NNP cord-014597-66vd2mdu 2311 10 Differentiation Differentiation NNP cord-014597-66vd2mdu 2311 11 Medium Medium NNP cord-014597-66vd2mdu 2311 12 ( ( -LRB- cord-014597-66vd2mdu 2311 13 InSCREENeX inscreenex NN cord-014597-66vd2mdu 2311 14 , , , cord-014597-66vd2mdu 2311 15 Germany Germany NNP cord-014597-66vd2mdu 2311 16 ) ) -RRB- cord-014597-66vd2mdu 2311 17 . . . cord-014597-66vd2mdu 2312 1 " " `` cord-014597-66vd2mdu 2312 2 Mini mini JJ cord-014597-66vd2mdu 2312 3 bone bone NN cord-014597-66vd2mdu 2312 4 " " '' cord-014597-66vd2mdu 2312 5 tissue tissue NN cord-014597-66vd2mdu 2312 6 functionality functionality NN cord-014597-66vd2mdu 2312 7 and and CC cord-014597-66vd2mdu 2312 8 thus thus RB cord-014597-66vd2mdu 2312 9 mineralization mineralization NN cord-014597-66vd2mdu 2312 10 was be VBD cord-014597-66vd2mdu 2312 11 analyzed analyze VBN cord-014597-66vd2mdu 2312 12 by by IN cord-014597-66vd2mdu 2312 13 an an DT cord-014597-66vd2mdu 2312 14 alkaline alkaline JJ cord-014597-66vd2mdu 2312 15 phosphatase phosphatase NN cord-014597-66vd2mdu 2312 16 ( ( -LRB- cord-014597-66vd2mdu 2312 17 alkaline alkaline JJ cord-014597-66vd2mdu 2312 18 phosphatase phosphatase NN cord-014597-66vd2mdu 2312 19 activity activity NN cord-014597-66vd2mdu 2312 20 ) ) -RRB- cord-014597-66vd2mdu 2312 21 and and CC cord-014597-66vd2mdu 2312 22 an an DT cord-014597-66vd2mdu 2312 23 alizarin alizarin JJ cord-014597-66vd2mdu 2312 24 red red JJ cord-014597-66vd2mdu 2312 25 S s NN cord-014597-66vd2mdu 2312 26 Staining Staining NNP cord-014597-66vd2mdu 2312 27 ( ( -LRB- cord-014597-66vd2mdu 2312 28 Ca Ca NNP cord-014597-66vd2mdu 2312 29 2 2 CD cord-014597-66vd2mdu 2312 30 + + SYM cord-014597-66vd2mdu 2312 31 deposits deposit NNS cord-014597-66vd2mdu 2312 32 ) ) -RRB- cord-014597-66vd2mdu 2312 33 . . . cord-014597-66vd2mdu 2313 1 The the DT cord-014597-66vd2mdu 2313 2 combination combination NN cord-014597-66vd2mdu 2313 3 of of IN cord-014597-66vd2mdu 2313 4 CI CI NNP cord-014597-66vd2mdu 2313 5 - - HYPH cord-014597-66vd2mdu 2313 6 huOB huOB NNP cord-014597-66vd2mdu 2313 7 cells cell NNS cord-014597-66vd2mdu 2313 8 with with IN cord-014597-66vd2mdu 2313 9 the the DT cord-014597-66vd2mdu 2313 10 magnetic magnetic JJ cord-014597-66vd2mdu 2313 11 3D 3D NNP cord-014597-66vd2mdu 2313 12 bioprinting bioprinting NNP cord-014597-66vd2mdu 2313 13 technology technology NN cord-014597-66vd2mdu 2313 14 enabled enable VBD cord-014597-66vd2mdu 2313 15 the the DT cord-014597-66vd2mdu 2313 16 establishment establishment NN cord-014597-66vd2mdu 2313 17 of of IN cord-014597-66vd2mdu 2313 18 reproducible reproducible JJ cord-014597-66vd2mdu 2313 19 and and CC cord-014597-66vd2mdu 2313 20 consistent consistent JJ cord-014597-66vd2mdu 2313 21 3D 3d JJ cord-014597-66vd2mdu 2313 22 spheroids spheroid NNS cord-014597-66vd2mdu 2313 23 . . . cord-014597-66vd2mdu 2314 1 Single single JJ cord-014597-66vd2mdu 2314 2 spheroids spheroid NNS cord-014597-66vd2mdu 2314 3 per per IN cord-014597-66vd2mdu 2314 4 well well RB cord-014597-66vd2mdu 2314 5 were be VBD cord-014597-66vd2mdu 2314 6 formed form VBN cord-014597-66vd2mdu 2314 7 independent independent JJ cord-014597-66vd2mdu 2314 8 of of IN cord-014597-66vd2mdu 2314 9 the the DT cord-014597-66vd2mdu 2314 10 amount amount NN cord-014597-66vd2mdu 2314 11 of of IN cord-014597-66vd2mdu 2314 12 cells cell NNS cord-014597-66vd2mdu 2314 13 ( ( -LRB- cord-014597-66vd2mdu 2314 14 1.000 1.000 CD cord-014597-66vd2mdu 2314 15 - - SYM cord-014597-66vd2mdu 2314 16 50.000 50.000 CD cord-014597-66vd2mdu 2314 17 cells cell NNS cord-014597-66vd2mdu 2314 18 ) ) -RRB- cord-014597-66vd2mdu 2315 1 ( ( -LRB- cord-014597-66vd2mdu 2315 2 Fig Fig NNP cord-014597-66vd2mdu 2315 3 . . . cord-014597-66vd2mdu 2315 4 1a 1a CD cord-014597-66vd2mdu 2315 5 ) ) -RRB- cord-014597-66vd2mdu 2315 6 . . . cord-014597-66vd2mdu 2316 1 Formed form VBN cord-014597-66vd2mdu 2316 2 spheroids spheroid NNS cord-014597-66vd2mdu 2316 3 were be VBD cord-014597-66vd2mdu 2316 4 stable stable JJ cord-014597-66vd2mdu 2316 5 for for IN cord-014597-66vd2mdu 2316 6 a a DT cord-014597-66vd2mdu 2316 7 culture culture NN cord-014597-66vd2mdu 2316 8 period period NN cord-014597-66vd2mdu 2316 9 of of IN cord-014597-66vd2mdu 2316 10 up up IN cord-014597-66vd2mdu 2316 11 to to TO cord-014597-66vd2mdu 2316 12 50 50 CD cord-014597-66vd2mdu 2316 13 days day NNS cord-014597-66vd2mdu 2316 14 ( ( -LRB- cord-014597-66vd2mdu 2316 15 Fig fig NN cord-014597-66vd2mdu 2316 16 . . . cord-014597-66vd2mdu 2316 17 1b 1b CD cord-014597-66vd2mdu 2316 18 ) ) -RRB- cord-014597-66vd2mdu 2316 19 . . . cord-014597-66vd2mdu 2317 1 Neither neither DT cord-014597-66vd2mdu 2317 2 cell cell NN cord-014597-66vd2mdu 2317 3 death death NN cord-014597-66vd2mdu 2317 4 nor nor CC cord-014597-66vd2mdu 2317 5 cell cell NN cord-014597-66vd2mdu 2317 6 proliferation proliferation NN cord-014597-66vd2mdu 2317 7 were be VBD cord-014597-66vd2mdu 2317 8 observed observe VBN cord-014597-66vd2mdu 2317 9 in in IN cord-014597-66vd2mdu 2317 10 the the DT cord-014597-66vd2mdu 2317 11 bioprinted bioprinte VBN cord-014597-66vd2mdu 2317 12 spheroids spheroid NNS cord-014597-66vd2mdu 2317 13 which which WDT cord-014597-66vd2mdu 2317 14 is be VBZ cord-014597-66vd2mdu 2317 15 indicated indicate VBN cord-014597-66vd2mdu 2317 16 by by IN cord-014597-66vd2mdu 2317 17 the the DT cord-014597-66vd2mdu 2317 18 stable stable JJ cord-014597-66vd2mdu 2317 19 size size NN cord-014597-66vd2mdu 2317 20 of of IN cord-014597-66vd2mdu 2317 21 the the DT cord-014597-66vd2mdu 2317 22 spheroids spheroid NNS cord-014597-66vd2mdu 2317 23 throughout throughout IN cord-014597-66vd2mdu 2317 24 the the DT cord-014597-66vd2mdu 2317 25 cultivation cultivation NN cord-014597-66vd2mdu 2317 26 ( ( -LRB- cord-014597-66vd2mdu 2317 27 Fig Fig NNP cord-014597-66vd2mdu 2317 28 . . . cord-014597-66vd2mdu 2317 29 1c 1c CD cord-014597-66vd2mdu 2317 30 ) ) -RRB- cord-014597-66vd2mdu 2317 31 . . . cord-014597-66vd2mdu 2318 1 After after IN cord-014597-66vd2mdu 2318 2 treatment treatment NN cord-014597-66vd2mdu 2318 3 with with IN cord-014597-66vd2mdu 2318 4 a a DT cord-014597-66vd2mdu 2318 5 differentiation differentiation NN cord-014597-66vd2mdu 2318 6 stimulus stimulus NN cord-014597-66vd2mdu 2318 7 the the DT cord-014597-66vd2mdu 2318 8 3D 3D NNP cord-014597-66vd2mdu 2318 9 bioprinted bioprinted NNP cord-014597-66vd2mdu 2318 10 spheroids spheroid NNS cord-014597-66vd2mdu 2318 11 became become VBD cord-014597-66vd2mdu 2318 12 fully fully RB cord-014597-66vd2mdu 2318 13 functional functional JJ cord-014597-66vd2mdu 2318 14 " " '' cord-014597-66vd2mdu 2318 15 mini mini JJ cord-014597-66vd2mdu 2318 16 bones bone NNS cord-014597-66vd2mdu 2318 17 " " '' cord-014597-66vd2mdu 2318 18 . . . cord-014597-66vd2mdu 2319 1 This this DT cord-014597-66vd2mdu 2319 2 was be VBD cord-014597-66vd2mdu 2319 3 highlighted highlight VBN cord-014597-66vd2mdu 2319 4 by by IN cord-014597-66vd2mdu 2319 5 the the DT cord-014597-66vd2mdu 2319 6 alkaline alkaline JJ cord-014597-66vd2mdu 2319 7 phosphatase phosphatase NN cord-014597-66vd2mdu 2319 8 activity activity NN cord-014597-66vd2mdu 2319 9 and and CC cord-014597-66vd2mdu 2319 10 the the DT cord-014597-66vd2mdu 2319 11 Ca Ca NNP cord-014597-66vd2mdu 2319 12 2 2 CD cord-014597-66vd2mdu 2319 13 + + SYM cord-014597-66vd2mdu 2319 14 deposits deposit NNS cord-014597-66vd2mdu 2319 15 within within IN cord-014597-66vd2mdu 2319 16 the the DT cord-014597-66vd2mdu 2319 17 3D 3D NNP cord-014597-66vd2mdu 2319 18 bioprinted bioprinte VBN cord-014597-66vd2mdu 2319 19 spheroids spheroid NNS cord-014597-66vd2mdu 2319 20 ( ( -LRB- cord-014597-66vd2mdu 2319 21 Fig Fig NNP cord-014597-66vd2mdu 2319 22 . . NNP cord-014597-66vd2mdu 2319 23 1d 1d NNP cord-014597-66vd2mdu 2319 24 , , , cord-014597-66vd2mdu 2319 25 e e LS cord-014597-66vd2mdu 2319 26 ) ) -RRB- cord-014597-66vd2mdu 2319 27 . . . cord-014597-66vd2mdu 2320 1 Taken take VBN cord-014597-66vd2mdu 2320 2 together together RB cord-014597-66vd2mdu 2320 3 , , , cord-014597-66vd2mdu 2320 4 these these DT cord-014597-66vd2mdu 2320 5 results result NNS cord-014597-66vd2mdu 2320 6 demonstrated demonstrate VBD cord-014597-66vd2mdu 2320 7 that that IN cord-014597-66vd2mdu 2320 8 the the DT cord-014597-66vd2mdu 2320 9 functional functional JJ cord-014597-66vd2mdu 2320 10 immortalization immortalization NN cord-014597-66vd2mdu 2320 11 technology technology NN cord-014597-66vd2mdu 2320 12 provides provide VBZ cord-014597-66vd2mdu 2320 13 physiologically physiologically RB cord-014597-66vd2mdu 2320 14 relevant relevant JJ cord-014597-66vd2mdu 2320 15 cells cell NNS cord-014597-66vd2mdu 2320 16 in in IN cord-014597-66vd2mdu 2320 17 sufficient sufficient JJ cord-014597-66vd2mdu 2320 18 numbers number NNS cord-014597-66vd2mdu 2320 19 and and CC cord-014597-66vd2mdu 2320 20 that that IN cord-014597-66vd2mdu 2320 21 the the DT cord-014597-66vd2mdu 2320 22 magnetic magnetic JJ cord-014597-66vd2mdu 2320 23 3D 3D NNP cord-014597-66vd2mdu 2320 24 Bioprinting Bioprinting NNP cord-014597-66vd2mdu 2320 25 technology technology NN cord-014597-66vd2mdu 2320 26 enabled enable VBD cord-014597-66vd2mdu 2320 27 a a DT cord-014597-66vd2mdu 2320 28 fast fast JJ cord-014597-66vd2mdu 2320 29 , , , cord-014597-66vd2mdu 2320 30 consistent consistent JJ cord-014597-66vd2mdu 2320 31 cell cell NN cord-014597-66vd2mdu 2320 32 aggregation aggregation NN cord-014597-66vd2mdu 2320 33 and and CC cord-014597-66vd2mdu 2320 34 the the DT cord-014597-66vd2mdu 2320 35 formation formation NN cord-014597-66vd2mdu 2320 36 of of IN cord-014597-66vd2mdu 2320 37 stable stable JJ cord-014597-66vd2mdu 2320 38 uniform uniform JJ cord-014597-66vd2mdu 2320 39 spheroids spheroid NNS cord-014597-66vd2mdu 2320 40 . . . cord-014597-66vd2mdu 2321 1 Importantly importantly RB cord-014597-66vd2mdu 2321 2 , , , cord-014597-66vd2mdu 2321 3 these these DT cord-014597-66vd2mdu 2321 4 immortalized immortalize VBN cord-014597-66vd2mdu 2321 5 cells cell NNS cord-014597-66vd2mdu 2321 6 are be VBP cord-014597-66vd2mdu 2321 7 capable capable JJ cord-014597-66vd2mdu 2321 8 to to TO cord-014597-66vd2mdu 2321 9 differentiate differentiate VB cord-014597-66vd2mdu 2321 10 when when WRB cord-014597-66vd2mdu 2321 11 a a DT cord-014597-66vd2mdu 2321 12 suitable suitable JJ cord-014597-66vd2mdu 2321 13 stimulus stimulus NN cord-014597-66vd2mdu 2321 14 is be VBZ cord-014597-66vd2mdu 2321 15 provided provide VBN cord-014597-66vd2mdu 2321 16 . . . cord-014597-66vd2mdu 2322 1 For for IN cord-014597-66vd2mdu 2322 2 differentiation differentiation NN cord-014597-66vd2mdu 2322 3 into into IN cord-014597-66vd2mdu 2322 4 mini mini JJ cord-014597-66vd2mdu 2322 5 bones bone NNS cord-014597-66vd2mdu 2322 6 , , , cord-014597-66vd2mdu 2322 7 3D 3d JJ cord-014597-66vd2mdu 2322 8 spheroid spheroid NN cord-014597-66vd2mdu 2322 9 cultivation cultivation NN cord-014597-66vd2mdu 2322 10 and and CC cord-014597-66vd2mdu 2322 11 additional additional JJ cord-014597-66vd2mdu 2322 12 stimulation stimulation NN cord-014597-66vd2mdu 2322 13 by by IN cord-014597-66vd2mdu 2322 14 small small JJ cord-014597-66vd2mdu 2322 15 molecules molecule NNS cord-014597-66vd2mdu 2322 16 are be VBP cord-014597-66vd2mdu 2322 17 required require VBN cord-014597-66vd2mdu 2322 18 . . . cord-014597-66vd2mdu 2323 1 The the DT cord-014597-66vd2mdu 2323 2 combination combination NN cord-014597-66vd2mdu 2323 3 of of IN cord-014597-66vd2mdu 2323 4 physiologically physiologically RB cord-014597-66vd2mdu 2323 5 relevant relevant JJ cord-014597-66vd2mdu 2323 6 cell cell NN cord-014597-66vd2mdu 2323 7 systems system NNS cord-014597-66vd2mdu 2323 8 with with IN cord-014597-66vd2mdu 2323 9 three three CD cord-014597-66vd2mdu 2323 10 dimensional dimensional JJ cord-014597-66vd2mdu 2323 11 culturing culturing NN cord-014597-66vd2mdu 2323 12 will will MD cord-014597-66vd2mdu 2323 13 help help VB cord-014597-66vd2mdu 2323 14 to to TO cord-014597-66vd2mdu 2323 15 generate generate VB cord-014597-66vd2mdu 2323 16 in in IN cord-014597-66vd2mdu 2323 17 vitro vitro FW cord-014597-66vd2mdu 2323 18 test test NN cord-014597-66vd2mdu 2323 19 systems system NNS cord-014597-66vd2mdu 2323 20 which which WDT cord-014597-66vd2mdu 2323 21 closely closely RB cord-014597-66vd2mdu 2323 22 resemble resemble VBP cord-014597-66vd2mdu 2323 23 the the DT cord-014597-66vd2mdu 2323 24 in in IN cord-014597-66vd2mdu 2323 25 vivo vivo NN cord-014597-66vd2mdu 2323 26 physiology physiology NN cord-014597-66vd2mdu 2323 27 and and CC cord-014597-66vd2mdu 2323 28 thereby thereby RB cord-014597-66vd2mdu 2323 29 supporting support VBG cord-014597-66vd2mdu 2323 30 future future JJ cord-014597-66vd2mdu 2323 31 drug drug NN cord-014597-66vd2mdu 2323 32 discovery discovery NN cord-014597-66vd2mdu 2323 33 approaches approach NNS cord-014597-66vd2mdu 2323 34 . . . cord-014597-66vd2mdu 2324 1 Fig Fig NNP cord-014597-66vd2mdu 2324 2 . . . cord-014597-66vd2mdu 2324 3 1 1 CD cord-014597-66vd2mdu 2324 4 ( ( -LRB- cord-014597-66vd2mdu 2324 5 abstract abstract NNP cord-014597-66vd2mdu 2324 6 P-381 P-381 NNP cord-014597-66vd2mdu 2324 7 ) ) -RRB- cord-014597-66vd2mdu 2324 8 . . . cord-014597-66vd2mdu 2325 1 Characterization characterization NN cord-014597-66vd2mdu 2325 2 of of IN cord-014597-66vd2mdu 2325 3 spheroid spheroid NN cord-014597-66vd2mdu 2325 4 " " `` cord-014597-66vd2mdu 2325 5 mini mini JJ cord-014597-66vd2mdu 2325 6 bones bone NNS cord-014597-66vd2mdu 2325 7 " " '' cord-014597-66vd2mdu 2325 8 . . . cord-014597-66vd2mdu 2326 1 a a DT cord-014597-66vd2mdu 2326 2 Different different JJ cord-014597-66vd2mdu 2326 3 number number NN cord-014597-66vd2mdu 2326 4 ( ( -LRB- cord-014597-66vd2mdu 2326 5 1.000 1.000 CD cord-014597-66vd2mdu 2326 6 - - SYM cord-014597-66vd2mdu 2326 7 50.000 50.000 CD cord-014597-66vd2mdu 2326 8 cells cell NNS cord-014597-66vd2mdu 2326 9 ) ) -RRB- cord-014597-66vd2mdu 2326 10 of of IN cord-014597-66vd2mdu 2326 11 CI CI NNP cord-014597-66vd2mdu 2326 12 - - HYPH cord-014597-66vd2mdu 2326 13 huOB huOB NNP cord-014597-66vd2mdu 2326 14 cells cell NNS cord-014597-66vd2mdu 2326 15 were be VBD cord-014597-66vd2mdu 2326 16 printed print VBN cord-014597-66vd2mdu 2326 17 into into IN cord-014597-66vd2mdu 2326 18 spheroids spheroid NNS cord-014597-66vd2mdu 2326 19 . . . cord-014597-66vd2mdu 2327 1 b b LS cord-014597-66vd2mdu 2327 2 20.000 20.000 CD cord-014597-66vd2mdu 2327 3 CI CI NNP cord-014597-66vd2mdu 2327 4 - - HYPH cord-014597-66vd2mdu 2327 5 huOBs huOBs NNP cord-014597-66vd2mdu 2327 6 were be VBD cord-014597-66vd2mdu 2327 7 printed print VBN cord-014597-66vd2mdu 2327 8 into into IN cord-014597-66vd2mdu 2327 9 spheroids spheroid NNS cord-014597-66vd2mdu 2327 10 and and CC cord-014597-66vd2mdu 2327 11 cultivated cultivate VBN cord-014597-66vd2mdu 2327 12 for for IN cord-014597-66vd2mdu 2327 13 indicated indicate VBN cord-014597-66vd2mdu 2327 14 time time NN cord-014597-66vd2mdu 2327 15 points point NNS cord-014597-66vd2mdu 2327 16 . . . cord-014597-66vd2mdu 2328 1 c c NNP cord-014597-66vd2mdu 2329 1 For for IN cord-014597-66vd2mdu 2329 2 analyzing analyze VBG cord-014597-66vd2mdu 2329 3 spheroid spheroid NN cord-014597-66vd2mdu 2329 4 sizes size NNS cord-014597-66vd2mdu 2329 5 , , , cord-014597-66vd2mdu 2329 6 pictures picture NNS cord-014597-66vd2mdu 2329 7 were be VBD cord-014597-66vd2mdu 2329 8 taken take VBN cord-014597-66vd2mdu 2329 9 and and CC cord-014597-66vd2mdu 2329 10 quantified quantify VBN cord-014597-66vd2mdu 2329 11 by by IN cord-014597-66vd2mdu 2330 1 ImageJ. ImageJ. NNP cord-014597-66vd2mdu 2330 2 ( ( -LRB- cord-014597-66vd2mdu 2330 3 D D NNP cord-014597-66vd2mdu 2330 4 / / SYM cord-014597-66vd2mdu 2330 5 E e NN cord-014597-66vd2mdu 2330 6 ) ) -RRB- cord-014597-66vd2mdu 2330 7 20.000 20.000 CD cord-014597-66vd2mdu 2330 8 CI CI NNP cord-014597-66vd2mdu 2330 9 - - HYPH cord-014597-66vd2mdu 2330 10 huOB huOB NNP cord-014597-66vd2mdu 2330 11 cells cell NNS cord-014597-66vd2mdu 2330 12 were be VBD cord-014597-66vd2mdu 2330 13 printed print VBN cord-014597-66vd2mdu 2330 14 into into IN cord-014597-66vd2mdu 2330 15 spheroids spheroid NNS cord-014597-66vd2mdu 2330 16 and and CC cord-014597-66vd2mdu 2330 17 cultivated cultivate VBN cord-014597-66vd2mdu 2330 18 with with IN cord-014597-66vd2mdu 2330 19 ( ( -LRB- cord-014597-66vd2mdu 2330 20 huOB huOB NNP cord-014597-66vd2mdu 2330 21 Differentiation Differentiation NNP cord-014597-66vd2mdu 2330 22 Medium Medium NNP cord-014597-66vd2mdu 2330 23 ) ) -RRB- cord-014597-66vd2mdu 2330 24 or or CC cord-014597-66vd2mdu 2330 25 without without IN cord-014597-66vd2mdu 2330 26 a a DT cord-014597-66vd2mdu 2330 27 differentiation differentiation NN cord-014597-66vd2mdu 2330 28 stimulus stimulus NN cord-014597-66vd2mdu 2330 29 for for IN cord-014597-66vd2mdu 2330 30 two two CD cord-014597-66vd2mdu 2330 31 weeks week NNS cord-014597-66vd2mdu 2330 32 . . . cord-014597-66vd2mdu 2331 1 Afterwards afterwards RB cord-014597-66vd2mdu 2331 2 , , , cord-014597-66vd2mdu 2331 3 bioprinted bioprinted JJ cord-014597-66vd2mdu 2331 4 spheroids spheroid NNS cord-014597-66vd2mdu 2331 5 were be VBD cord-014597-66vd2mdu 2331 6 sectioned section VBN cord-014597-66vd2mdu 2331 7 by by IN cord-014597-66vd2mdu 2331 8 a a DT cord-014597-66vd2mdu 2331 9 cryo cryo NN cord-014597-66vd2mdu 2331 10 microtome microtome NN cord-014597-66vd2mdu 2331 11 and and CC cord-014597-66vd2mdu 2331 12 d d LS cord-014597-66vd2mdu 2331 13 stained stain VBN cord-014597-66vd2mdu 2331 14 for for IN cord-014597-66vd2mdu 2331 15 Ca Ca NNP cord-014597-66vd2mdu 2331 16 2 2 CD cord-014597-66vd2mdu 2331 17 + + SYM cord-014597-66vd2mdu 2331 18 deposits deposit NNS cord-014597-66vd2mdu 2331 19 ( ( -LRB- cord-014597-66vd2mdu 2331 20 Alizarin Alizarin NNP cord-014597-66vd2mdu 2331 21 Red Red NNP cord-014597-66vd2mdu 2331 22 S S NNP cord-014597-66vd2mdu 2331 23 ) ) -RRB- cord-014597-66vd2mdu 2331 24 or or CC cord-014597-66vd2mdu 2331 25 e e LS cord-014597-66vd2mdu 2331 26 stained stain VBN cord-014597-66vd2mdu 2331 27 for for IN cord-014597-66vd2mdu 2331 28 alkaline alkaline JJ cord-014597-66vd2mdu 2331 29 phosphatase phosphatase NN cord-014597-66vd2mdu 2331 30 activity activity NN cord-014597-66vd2mdu 2331 31 CRISPR CRISPR NNP cord-014597-66vd2mdu 2331 32 / / , cord-014597-66vd2mdu 2331 33 cas9 cas9 XX cord-014597-66vd2mdu 2331 34 , , , cord-014597-66vd2mdu 2331 35 a a DT cord-014597-66vd2mdu 2331 36 novel novel JJ cord-014597-66vd2mdu 2331 37 genomic genomic JJ cord-014597-66vd2mdu 2331 38 tool tool NN cord-014597-66vd2mdu 2331 39 to to TO cord-014597-66vd2mdu 2331 40 knock knock VB cord-014597-66vd2mdu 2331 41 down down RP cord-014597-66vd2mdu 2331 42 microRNA microRNA NNP cord-014597-66vd2mdu 2331 43 in in IN cord-014597-66vd2mdu 2331 44 vitro vitro FW cord-014597-66vd2mdu 2331 45 and and CC cord-014597-66vd2mdu 2331 46 in in IN cord-014597-66vd2mdu 2331 47 vivo vivo NNP cord-014597-66vd2mdu 2331 48 Degrontagged degrontagge VBN cord-014597-66vd2mdu 2331 49 dCas9 dCas9 NNP cord-014597-66vd2mdu 2331 50 / / SYM cord-014597-66vd2mdu 2331 51 Cpf1 Cpf1 NNP cord-014597-66vd2mdu 2331 52 Effectors Effectors NNP cord-014597-66vd2mdu 2331 53 for for IN cord-014597-66vd2mdu 2331 54 Multi multi JJ cord-014597-66vd2mdu 2331 55 - - JJ cord-014597-66vd2mdu 2331 56 directional directional JJ cord-014597-66vd2mdu 2331 57 Drug drug NN cord-014597-66vd2mdu 2331 58 - - HYPH cord-014597-66vd2mdu 2331 59 inducible inducible JJ cord-014597-66vd2mdu 2331 60 control control NN cord-014597-66vd2mdu 2331 61 of of IN cord-014597-66vd2mdu 2331 62 Synthetic Synthetic NNP cord-014597-66vd2mdu 2331 63 Gene Gene NNP cord-014597-66vd2mdu 2331 64 Regulation Regulation NNP cord-014597-66vd2mdu 2331 65 Assessing assess VBG cord-014597-66vd2mdu 2331 66 the the DT cord-014597-66vd2mdu 2331 67 Variability Variability NNP cord-014597-66vd2mdu 2331 68 of of IN cord-014597-66vd2mdu 2331 69 an an DT cord-014597-66vd2mdu 2331 70 Innovator Innovator NNP cord-014597-66vd2mdu 2331 71 Molecule Molecule NNP cord-014597-66vd2mdu 2331 72 N N NNP cord-014597-66vd2mdu 2331 73 - - HYPH cord-014597-66vd2mdu 2331 74 Glycan Glycan NNP cord-014597-66vd2mdu 2331 75 Profile Profile NNP cord-014597-66vd2mdu 2331 76 Correct correct VB cord-014597-66vd2mdu 2331 77 primary primary JJ cord-014597-66vd2mdu 2331 78 structure structure NN cord-014597-66vd2mdu 2331 79 assessment assessment NN cord-014597-66vd2mdu 2331 80 and and CC cord-014597-66vd2mdu 2331 81 extensive extensive JJ cord-014597-66vd2mdu 2331 82 glyco glyco NNP cord-014597-66vd2mdu 2331 83 - - HYPH cord-014597-66vd2mdu 2331 84 profiling profiling NN cord-014597-66vd2mdu 2331 85 of of IN cord-014597-66vd2mdu 2331 86 cetuximab cetuximab NNS cord-014597-66vd2mdu 2331 87 by by IN cord-014597-66vd2mdu 2331 88 a a DT cord-014597-66vd2mdu 2331 89 combination combination NN cord-014597-66vd2mdu 2331 90 of of IN cord-014597-66vd2mdu 2331 91 intact intact JJ cord-014597-66vd2mdu 2331 92 , , , cord-014597-66vd2mdu 2331 93 middle middle NN cord-014597-66vd2mdu 2331 94 - - HYPH cord-014597-66vd2mdu 2331 95 up up NN cord-014597-66vd2mdu 2331 96 , , , cord-014597-66vd2mdu 2331 97 middle middle NN cord-014597-66vd2mdu 2331 98 - - HYPH cord-014597-66vd2mdu 2331 99 down down NN cord-014597-66vd2mdu 2331 100 and and CC cord-014597-66vd2mdu 2331 101 bottom bottom NN cord-014597-66vd2mdu 2331 102 - - HYPH cord-014597-66vd2mdu 2331 103 up up NN cord-014597-66vd2mdu 2331 104 ESI ESI NNP cord-014597-66vd2mdu 2331 105 and and CC cord-014597-66vd2mdu 2331 106 MALDI MALDI NNP cord-014597-66vd2mdu 2331 107 mass mass NN cord-014597-66vd2mdu 2331 108 spectrometry spectrometry NN cord-014597-66vd2mdu 2331 109 techniques technique NNS cord-014597-66vd2mdu 2331 110 2D 2D NNP cord-014597-66vd2mdu 2331 111 - - HYPH cord-014597-66vd2mdu 2331 112 DIGE dige NN cord-014597-66vd2mdu 2331 113 screening screening NN cord-014597-66vd2mdu 2331 114 of of IN cord-014597-66vd2mdu 2331 115 high high JJ cord-014597-66vd2mdu 2331 116 productive productive JJ cord-014597-66vd2mdu 2331 117 CHO CHO NNP cord-014597-66vd2mdu 2331 118 cells cell NNS cord-014597-66vd2mdu 2331 119 under under IN cord-014597-66vd2mdu 2331 120 glucoselimitation glucoselimitation NN cord-014597-66vd2mdu 2331 121 -basic -basic HYPH cord-014597-66vd2mdu 2331 122 changes change NNS cord-014597-66vd2mdu 2331 123 in in IN cord-014597-66vd2mdu 2331 124 the the DT cord-014597-66vd2mdu 2331 125 proteome proteome NN cord-014597-66vd2mdu 2331 126 equipment equipment NN cord-014597-66vd2mdu 2331 127 and and CC cord-014597-66vd2mdu 2331 128 hints hint NNS cord-014597-66vd2mdu 2331 129 for for IN cord-014597-66vd2mdu 2331 130 epigenetic epigenetic JJ cord-014597-66vd2mdu 2331 131 effects effect NNS cord-014597-66vd2mdu 2331 132 Dependence dependence NN cord-014597-66vd2mdu 2331 133 on on IN cord-014597-66vd2mdu 2331 134 Glucose Glucose NNP cord-014597-66vd2mdu 2331 135 Limitation Limitation NNP cord-014597-66vd2mdu 2331 136 of of IN cord-014597-66vd2mdu 2331 137 the the DT cord-014597-66vd2mdu 2331 138 pCO2 pCO2 NNP cord-014597-66vd2mdu 2331 139 Influences Influences NNPS cord-014597-66vd2mdu 2331 140 on on IN cord-014597-66vd2mdu 2331 141 CHO CHO NNP cord-014597-66vd2mdu 2331 142 Cell Cell NNP cord-014597-66vd2mdu 2331 143 Growth Growth NNP cord-014597-66vd2mdu 2331 144 , , , cord-014597-66vd2mdu 2331 145 Metabolism metabolism NN cord-014597-66vd2mdu 2331 146 and and CC cord-014597-66vd2mdu 2331 147 IgG IgG NNP cord-014597-66vd2mdu 2331 148 Production Production NNP cord-014597-66vd2mdu 2331 149 Fcgalactosylation Fcgalactosylation NNP cord-014597-66vd2mdu 2331 150 modulates modulate VBZ cord-014597-66vd2mdu 2331 151 antibody antibody NN cord-014597-66vd2mdu 2331 152 - - HYPH cord-014597-66vd2mdu 2331 153 dependent dependent JJ cord-014597-66vd2mdu 2331 154 cellular cellular JJ cord-014597-66vd2mdu 2331 155 cytotoxicity cytotoxicity NN cord-014597-66vd2mdu 2331 156 of of IN cord-014597-66vd2mdu 2331 157 therapeutic therapeutic JJ cord-014597-66vd2mdu 2331 158 antibodies antibody NNS cord-014597-66vd2mdu 2332 1 Fc Fc NNP cord-014597-66vd2mdu 2332 2 glycans glycan NNS cord-014597-66vd2mdu 2332 3 of of IN cord-014597-66vd2mdu 2332 4 therapeutic therapeutic JJ cord-014597-66vd2mdu 2332 5 antibodies antibody NNS cord-014597-66vd2mdu 2332 6 as as IN cord-014597-66vd2mdu 2332 7 critical critical JJ cord-014597-66vd2mdu 2332 8 quality quality NN cord-014597-66vd2mdu 2332 9 attributes attribute VBZ cord-014597-66vd2mdu 2332 10 Development Development NNP cord-014597-66vd2mdu 2332 11 of of IN cord-014597-66vd2mdu 2332 12 an an DT cord-014597-66vd2mdu 2332 13 automated automated JJ cord-014597-66vd2mdu 2332 14 , , , cord-014597-66vd2mdu 2332 15 multiwell multiwell NNP cord-014597-66vd2mdu 2332 16 plate plate NN cord-014597-66vd2mdu 2332 17 based base VBN cord-014597-66vd2mdu 2332 18 screening screening NN cord-014597-66vd2mdu 2332 19 system system NN cord-014597-66vd2mdu 2332 20 for for IN cord-014597-66vd2mdu 2332 21 suspension suspension NN cord-014597-66vd2mdu 2332 22 cell cell NN cord-014597-66vd2mdu 2332 23 culture culture NN cord-014597-66vd2mdu 2333 1 Global global JJ cord-014597-66vd2mdu 2333 2 cancer cancer NN cord-014597-66vd2mdu 2333 3 statistics statistic NNS cord-014597-66vd2mdu 2333 4 Remission remission NN cord-014597-66vd2mdu 2333 5 of of IN cord-014597-66vd2mdu 2333 6 disseminated disseminate VBN cord-014597-66vd2mdu 2333 7 cancer cancer NN cord-014597-66vd2mdu 2333 8 after after IN cord-014597-66vd2mdu 2333 9 systemic systemic JJ cord-014597-66vd2mdu 2333 10 oncolytic oncolytic VBN cord-014597-66vd2mdu 2333 11 virotherapy virotherapy NN cord-014597-66vd2mdu 2334 1 Screening screen VBG cord-014597-66vd2mdu 2334 2 different different JJ cord-014597-66vd2mdu 2334 3 host host NN cord-014597-66vd2mdu 2334 4 cell cell NN cord-014597-66vd2mdu 2334 5 lines line NNS cord-014597-66vd2mdu 2334 6 for for IN cord-014597-66vd2mdu 2334 7 the the DT cord-014597-66vd2mdu 2334 8 dynamic dynamic JJ cord-014597-66vd2mdu 2334 9 production production NN cord-014597-66vd2mdu 2334 10 of of IN cord-014597-66vd2mdu 2334 11 measles measle NNS cord-014597-66vd2mdu 2334 12 virus virus NN cord-014597-66vd2mdu 2335 1 Beitrag Beitrag NNP cord-014597-66vd2mdu 2335 2 zur zur NNP cord-014597-66vd2mdu 2335 3 kollektiven kollektiven NNP cord-014597-66vd2mdu 2335 4 Behandlung Behandlung NNP cord-014597-66vd2mdu 2335 5 pharmakologischer pharmakologischer NNP cord-014597-66vd2mdu 2336 1 Reihenversuche reihenversuche NN cord-014597-66vd2mdu 2337 1 A a DT cord-014597-66vd2mdu 2337 2 simple simple JJ cord-014597-66vd2mdu 2337 3 method method NN cord-014597-66vd2mdu 2337 4 of of IN cord-014597-66vd2mdu 2337 5 estimating estimate VBG cord-014597-66vd2mdu 2337 6 fifty fifty CD cord-014597-66vd2mdu 2337 7 per per IN cord-014597-66vd2mdu 2337 8 cent cent NN cord-014597-66vd2mdu 2337 9 endpoints endpoint NNS cord-014597-66vd2mdu 2337 10 Webinar Webinar NNP cord-014597-66vd2mdu 2337 11 : : : cord-014597-66vd2mdu 2337 12 ambr15 ambr15 NN cord-014597-66vd2mdu 2337 13 as as IN cord-014597-66vd2mdu 2337 14 a a DT cord-014597-66vd2mdu 2337 15 sedimentation sedimentation NN cord-014597-66vd2mdu 2337 16 - - HYPH cord-014597-66vd2mdu 2337 17 perfusion perfusion NN cord-014597-66vd2mdu 2337 18 model model NN cord-014597-66vd2mdu 2337 19 for for IN cord-014597-66vd2mdu 2337 20 cultivation cultivation NN cord-014597-66vd2mdu 2337 21 characteristics characteristic NNS cord-014597-66vd2mdu 2337 22 and and CC cord-014597-66vd2mdu 2337 23 product product NN cord-014597-66vd2mdu 2337 24 quality quality NN cord-014597-66vd2mdu 2337 25 prediction prediction NN cord-014597-66vd2mdu 2337 26 De De NNP cord-014597-66vd2mdu 2337 27 novo novo NNP cord-014597-66vd2mdu 2337 28 " " `` cord-014597-66vd2mdu 2337 29 high high JJ cord-014597-66vd2mdu 2337 30 density density NN cord-014597-66vd2mdu 2337 31 perfusion perfusion NN cord-014597-66vd2mdu 2337 32 medium medium NN cord-014597-66vd2mdu 2337 33 : : : cord-014597-66vd2mdu 2337 34 increased increase VBN cord-014597-66vd2mdu 2337 35 productivity productivity NN cord-014597-66vd2mdu 2337 36 and and CC cord-014597-66vd2mdu 2337 37 reduced reduce VBN cord-014597-66vd2mdu 2337 38 perfusion perfusion NN cord-014597-66vd2mdu 2337 39 rates rate NNS cord-014597-66vd2mdu 2338 1 A a DT cord-014597-66vd2mdu 2338 2 high high RB cord-014597-66vd2mdu 2338 3 - - HYPH cord-014597-66vd2mdu 2338 4 yielding yield VBG cord-014597-66vd2mdu 2338 5 CHO CHO NNP cord-014597-66vd2mdu 2338 6 transient transient JJ cord-014597-66vd2mdu 2338 7 system system NN cord-014597-66vd2mdu 2338 8 : : : cord-014597-66vd2mdu 2338 9 Co co NN cord-014597-66vd2mdu 2338 10 - - NN cord-014597-66vd2mdu 2338 11 expression expression NN cord-014597-66vd2mdu 2338 12 of of IN cord-014597-66vd2mdu 2338 13 genes gene NNS cord-014597-66vd2mdu 2338 14 encoding encode VBG cord-014597-66vd2mdu 2338 15 EBNA-1 EBNA-1 NNP cord-014597-66vd2mdu 2338 16 and and CC cord-014597-66vd2mdu 2338 17 GS GS NNP cord-014597-66vd2mdu 2338 18 enhances enhance VBZ cord-014597-66vd2mdu 2338 19 transient transient JJ cord-014597-66vd2mdu 2338 20 protein protein NN cord-014597-66vd2mdu 2338 21 expression expression NN cord-014597-66vd2mdu 2339 1 An an DT cord-014597-66vd2mdu 2339 2 integrated integrated JJ cord-014597-66vd2mdu 2339 3 vector vector NN cord-014597-66vd2mdu 2339 4 system system NN cord-014597-66vd2mdu 2339 5 for for IN cord-014597-66vd2mdu 2339 6 the the DT cord-014597-66vd2mdu 2339 7 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 2339 8 expression expression NN cord-014597-66vd2mdu 2339 9 of of IN cord-014597-66vd2mdu 2339 10 antibodies antibody NNS cord-014597-66vd2mdu 2339 11 or or CC cord-014597-66vd2mdu 2339 12 their -PRON- PRP$ cord-014597-66vd2mdu 2339 13 fragments fragment NNS cord-014597-66vd2mdu 2339 14 after after IN cord-014597-66vd2mdu 2339 15 selection selection NN cord-014597-66vd2mdu 2339 16 from from IN cord-014597-66vd2mdu 2339 17 phage phage NN cord-014597-66vd2mdu 2339 18 display display NN cord-014597-66vd2mdu 2339 19 libraries library NNS cord-014597-66vd2mdu 2339 20 Towards towards IN cord-014597-66vd2mdu 2339 21 the the DT cord-014597-66vd2mdu 2339 22 development development NN cord-014597-66vd2mdu 2339 23 of of IN cord-014597-66vd2mdu 2339 24 a a DT cord-014597-66vd2mdu 2339 25 surface surface NN cord-014597-66vd2mdu 2339 26 plasmon plasmon NN cord-014597-66vd2mdu 2339 27 resonance resonance NN cord-014597-66vd2mdu 2339 28 assay assay NN cord-014597-66vd2mdu 2339 29 to to TO cord-014597-66vd2mdu 2339 30 evaluate evaluate VB cord-014597-66vd2mdu 2339 31 the the DT cord-014597-66vd2mdu 2339 32 glycosylation glycosylation NN cord-014597-66vd2mdu 2339 33 pattern pattern NN cord-014597-66vd2mdu 2339 34 of of IN cord-014597-66vd2mdu 2339 35 monoclonal monoclonal JJ cord-014597-66vd2mdu 2339 36 antibodies antibody NNS cord-014597-66vd2mdu 2339 37 using use VBG cord-014597-66vd2mdu 2339 38 the the DT cord-014597-66vd2mdu 2339 39 extracellular extracellular JJ cord-014597-66vd2mdu 2339 40 domains domain NNS cord-014597-66vd2mdu 2339 41 of of IN cord-014597-66vd2mdu 2339 42 CD16a CD16a NNP cord-014597-66vd2mdu 2339 43 and and CC cord-014597-66vd2mdu 2339 44 CD64 CD64 NNP cord-014597-66vd2mdu 2339 45 Biotinylation Biotinylation NNP cord-014597-66vd2mdu 2339 46 of of IN cord-014597-66vd2mdu 2339 47 the the DT cord-014597-66vd2mdu 2339 48 Fc Fc NNP cord-014597-66vd2mdu 2339 49 gamma gamma NN cord-014597-66vd2mdu 2339 50 receptor receptor NN cord-014597-66vd2mdu 2339 51 ectodomains ectodomain NNS cord-014597-66vd2mdu 2339 52 by by IN cord-014597-66vd2mdu 2339 53 mammalian mammalian JJ cord-014597-66vd2mdu 2339 54 cell cell NN cord-014597-66vd2mdu 2339 55 co co NN cord-014597-66vd2mdu 2339 56 - - NN cord-014597-66vd2mdu 2339 57 transfection transfection JJ cord-014597-66vd2mdu 2339 58 : : : cord-014597-66vd2mdu 2339 59 application application NN cord-014597-66vd2mdu 2339 60 to to IN cord-014597-66vd2mdu 2339 61 the the DT cord-014597-66vd2mdu 2339 62 development development NN cord-014597-66vd2mdu 2339 63 of of IN cord-014597-66vd2mdu 2339 64 a a DT cord-014597-66vd2mdu 2339 65 surface surface NN cord-014597-66vd2mdu 2339 66 plasmon plasmon JJ cord-014597-66vd2mdu 2339 67 resonance resonance NN cord-014597-66vd2mdu 2339 68 - - HYPH cord-014597-66vd2mdu 2339 69 based base VBN cord-014597-66vd2mdu 2339 70 assay assay NN cord-014597-66vd2mdu 2339 71 ambr ambr NNP cord-014597-66vd2mdu 2339 72 ™ ™ NNP cord-014597-66vd2mdu 2339 73 Mini mini JJ cord-014597-66vd2mdu 2339 74 - - HYPH cord-014597-66vd2mdu 2339 75 bioreactor bioreactor NN cord-014597-66vd2mdu 2339 76 as as IN cord-014597-66vd2mdu 2339 77 a a DT cord-014597-66vd2mdu 2339 78 High High NNP cord-014597-66vd2mdu 2339 79 - - HYPH cord-014597-66vd2mdu 2339 80 Throughput throughput NN cord-014597-66vd2mdu 2339 81 Tool tool NN cord-014597-66vd2mdu 2339 82 for for IN cord-014597-66vd2mdu 2339 83 Culture Culture NNP cord-014597-66vd2mdu 2339 84 Process Process NNP cord-014597-66vd2mdu 2339 85 Development Development NNP cord-014597-66vd2mdu 2339 86 to to TO cord-014597-66vd2mdu 2339 87 Accelerate accelerate VB cord-014597-66vd2mdu 2339 88 Transfer Transfer NNP cord-014597-66vd2mdu 2339 89 to to IN cord-014597-66vd2mdu 2339 90 Stainless Stainless NNP cord-014597-66vd2mdu 2339 91 Steel Steel NNP cord-014597-66vd2mdu 2339 92 Manufacturing Manufacturing NNP cord-014597-66vd2mdu 2339 93 Scale scale NN cord-014597-66vd2mdu 2340 1 : : : cord-014597-66vd2mdu 2340 2 Comparability comparability NN cord-014597-66vd2mdu 2340 3 study study NN cord-014597-66vd2mdu 2340 4 from from IN cord-014597-66vd2mdu 2340 5 Process Process NNP cord-014597-66vd2mdu 2340 6 Performance Performance NNP cord-014597-66vd2mdu 2340 7 to to IN cord-014597-66vd2mdu 2340 8 Product Product NNP cord-014597-66vd2mdu 2340 9 Quality quality NN cord-014597-66vd2mdu 2340 10 Attributes Attributes NNPS cord-014597-66vd2mdu 2340 11 Maximizing maximize VBG cord-014597-66vd2mdu 2340 12 binding bind VBG cord-014597-66vd2mdu 2340 13 capacity capacity NN cord-014597-66vd2mdu 2340 14 for for IN cord-014597-66vd2mdu 2340 15 protein protein NN cord-014597-66vd2mdu 2340 16 A a DT cord-014597-66vd2mdu 2340 17 chromatography chromatography NN cord-014597-66vd2mdu 2340 18 Protein Protein NNP cord-014597-66vd2mdu 2340 19 Glycosylation Glycosylation NNP cord-014597-66vd2mdu 2340 20 and and CC cord-014597-66vd2mdu 2340 21 its -PRON- PRP$ cord-014597-66vd2mdu 2340 22 Role role NN cord-014597-66vd2mdu 2340 23 in in IN cord-014597-66vd2mdu 2340 24 Protein Protein NNP cord-014597-66vd2mdu 2340 25 Folding Folding NNP cord-014597-66vd2mdu 2340 26 Afucosylated Afucosylated NNP cord-014597-66vd2mdu 2340 27 antibodies antibody NNS cord-014597-66vd2mdu 2340 28 increase increase VBP cord-014597-66vd2mdu 2340 29 activation activation NN cord-014597-66vd2mdu 2340 30 of of IN cord-014597-66vd2mdu 2340 31 FcγRIIIa fcγriiia NN cord-014597-66vd2mdu 2340 32 - - HYPH cord-014597-66vd2mdu 2340 33 dependent dependent JJ cord-014597-66vd2mdu 2340 34 signaling signal VBG cord-014597-66vd2mdu 2340 35 components component NNS cord-014597-66vd2mdu 2340 36 to to TO cord-014597-66vd2mdu 2340 37 intensify intensify VB cord-014597-66vd2mdu 2340 38 processes process NNS cord-014597-66vd2mdu 2340 39 promoting promote VBG cord-014597-66vd2mdu 2340 40 ADCC ADCC NNP cord-014597-66vd2mdu 2340 41 Sialic Sialic NNP cord-014597-66vd2mdu 2340 42 Acids Acids NNPS cord-014597-66vd2mdu 2340 43 and and CC cord-014597-66vd2mdu 2340 44 other other JJ cord-014597-66vd2mdu 2340 45 Nonulosonic Nonulosonic NNP cord-014597-66vd2mdu 2340 46 Acids Acids NNPS cord-014597-66vd2mdu 2340 47 Production Production NNP cord-014597-66vd2mdu 2340 48 of of IN cord-014597-66vd2mdu 2340 49 antibody antibody NN cord-014597-66vd2mdu 2340 50 in in IN cord-014597-66vd2mdu 2340 51 insect insect NN cord-014597-66vd2mdu 2340 52 cells cell NNS cord-014597-66vd2mdu 2340 53 Suitability suitability NN cord-014597-66vd2mdu 2340 54 and and CC cord-014597-66vd2mdu 2340 55 perspectives perspective NNS cord-014597-66vd2mdu 2340 56 on on IN cord-014597-66vd2mdu 2340 57 using use VBG cord-014597-66vd2mdu 2340 58 recombinant recombinant JJ cord-014597-66vd2mdu 2340 59 insect insect NN cord-014597-66vd2mdu 2340 60 cells cell NNS cord-014597-66vd2mdu 2340 61 for for IN cord-014597-66vd2mdu 2340 62 the the DT cord-014597-66vd2mdu 2340 63 production production NN cord-014597-66vd2mdu 2340 64 of of IN cord-014597-66vd2mdu 2340 65 virus virus NN cord-014597-66vd2mdu 2340 66 - - HYPH cord-014597-66vd2mdu 2340 67 like like JJ cord-014597-66vd2mdu 2340 68 particles particle NNS cord-014597-66vd2mdu 2340 69 Cloning clone VBG cord-014597-66vd2mdu 2340 70 of of IN cord-014597-66vd2mdu 2340 71 cDNA cdna NN cord-014597-66vd2mdu 2340 72 and and CC cord-014597-66vd2mdu 2340 73 characterization characterization NN cord-014597-66vd2mdu 2340 74 of of IN cord-014597-66vd2mdu 2340 75 anti anti JJ cord-014597-66vd2mdu 2340 76 - - JJ cord-014597-66vd2mdu 2340 77 RNase rnase JJ cord-014597-66vd2mdu 2340 78 A a DT cord-014597-66vd2mdu 2340 79 monoclonal monoclonal JJ cord-014597-66vd2mdu 2340 80 antibody antibody NN cord-014597-66vd2mdu 2340 81 3A21 3a21 CD cord-014597-66vd2mdu 2340 82 Production production NN cord-014597-66vd2mdu 2340 83 of of IN cord-014597-66vd2mdu 2340 84 functional functional JJ cord-014597-66vd2mdu 2340 85 antibody antibody NN cord-014597-66vd2mdu 2340 86 Fab fab JJ cord-014597-66vd2mdu 2340 87 fragment fragment NN cord-014597-66vd2mdu 2340 88 by by IN cord-014597-66vd2mdu 2340 89 recombinant recombinant JJ cord-014597-66vd2mdu 2340 90 insect insect NN cord-014597-66vd2mdu 2340 91 cells cell NNS cord-014597-66vd2mdu 2340 92 Optimization optimization NN cord-014597-66vd2mdu 2340 93 of of IN cord-014597-66vd2mdu 2340 94 HEK-293S hek-293s JJ cord-014597-66vd2mdu 2340 95 cell cell NN cord-014597-66vd2mdu 2340 96 cultures culture NNS cord-014597-66vd2mdu 2340 97 for for IN cord-014597-66vd2mdu 2340 98 the the DT cord-014597-66vd2mdu 2340 99 production production NN cord-014597-66vd2mdu 2340 100 of of IN cord-014597-66vd2mdu 2340 101 adenoviral adenoviral JJ cord-014597-66vd2mdu 2340 102 vectors vector NNS cord-014597-66vd2mdu 2340 103 in in IN cord-014597-66vd2mdu 2340 104 bioreactors bioreactor NNS cord-014597-66vd2mdu 2340 105 using use VBG cord-014597-66vd2mdu 2340 106 on on IN cord-014597-66vd2mdu 2340 107 - - HYPH cord-014597-66vd2mdu 2340 108 line line NN cord-014597-66vd2mdu 2340 109 OUR our PRP$ cord-014597-66vd2mdu 2340 110 measurements measurement NNS cord-014597-66vd2mdu 2340 111 Enhancing enhance VBG cord-014597-66vd2mdu 2340 112 heterologous heterologous JJ cord-014597-66vd2mdu 2340 113 protein protein NN cord-014597-66vd2mdu 2340 114 expression expression NN cord-014597-66vd2mdu 2340 115 and and CC cord-014597-66vd2mdu 2340 116 secretion secretion NN cord-014597-66vd2mdu 2340 117 in in IN cord-014597-66vd2mdu 2340 118 HEK293 HEK293 NNP cord-014597-66vd2mdu 2340 119 cells cell NNS cord-014597-66vd2mdu 2340 120 by by IN cord-014597-66vd2mdu 2340 121 means mean NNS cord-014597-66vd2mdu 2340 122 of of IN cord-014597-66vd2mdu 2340 123 combination combination NN cord-014597-66vd2mdu 2340 124 of of IN cord-014597-66vd2mdu 2340 125 CMV CMV NNP cord-014597-66vd2mdu 2340 126 promoter promoter NN cord-014597-66vd2mdu 2340 127 and and CC cord-014597-66vd2mdu 2340 128 IFNα2 ifnα2 JJ cord-014597-66vd2mdu 2340 129 signal signal NN cord-014597-66vd2mdu 2340 130 peptide peptide NN cord-014597-66vd2mdu 2340 131 HEK293 HEK293 NNP cord-014597-66vd2mdu 2340 132 cell cell NN cord-014597-66vd2mdu 2340 133 culture culture NN cord-014597-66vd2mdu 2340 134 media medium NNS cord-014597-66vd2mdu 2340 135 study study NN cord-014597-66vd2mdu 2340 136 towards towards IN cord-014597-66vd2mdu 2340 137 bioprocess bioprocess NN cord-014597-66vd2mdu 2340 138 optimization optimization NN cord-014597-66vd2mdu 2340 139 : : : cord-014597-66vd2mdu 2340 140 animal animal NN cord-014597-66vd2mdu 2340 141 derived derive VBN cord-014597-66vd2mdu 2340 142 component component NN cord-014597-66vd2mdu 2340 143 free free JJ cord-014597-66vd2mdu 2340 144 and and CC cord-014597-66vd2mdu 2340 145 animal animal NN cord-014597-66vd2mdu 2340 146 derived derive VBN cord-014597-66vd2mdu 2340 147 component component NN cord-014597-66vd2mdu 2340 148 containing contain VBG cord-014597-66vd2mdu 2340 149 platforms platform NNS cord-014597-66vd2mdu 2340 150 Comparison comparison NN cord-014597-66vd2mdu 2340 151 of of IN cord-014597-66vd2mdu 2340 152 control control NN cord-014597-66vd2mdu 2340 153 strategies strategy NNS cord-014597-66vd2mdu 2340 154 for for IN cord-014597-66vd2mdu 2340 155 fed fed JJ cord-014597-66vd2mdu 2340 156 - - HYPH cord-014597-66vd2mdu 2340 157 batch batch NN cord-014597-66vd2mdu 2340 158 culture culture NN cord-014597-66vd2mdu 2340 159 of of IN cord-014597-66vd2mdu 2340 160 hybridoma hybridoma NN cord-014597-66vd2mdu 2340 161 cells cell NNS cord-014597-66vd2mdu 2340 162 based base VBN cord-014597-66vd2mdu 2340 163 on on IN cord-014597-66vd2mdu 2340 164 on on IN cord-014597-66vd2mdu 2340 165 - - HYPH cord-014597-66vd2mdu 2340 166 line line NN cord-014597-66vd2mdu 2340 167 monitoring monitoring NN cord-014597-66vd2mdu 2340 168 of of IN cord-014597-66vd2mdu 2340 169 oxygen oxygen NN cord-014597-66vd2mdu 2340 170 uptake uptake NN cord-014597-66vd2mdu 2340 171 rate rate NN cord-014597-66vd2mdu 2340 172 , , , cord-014597-66vd2mdu 2340 173 optical optical JJ cord-014597-66vd2mdu 2340 174 cell cell NN cord-014597-66vd2mdu 2340 175 density density NN cord-014597-66vd2mdu 2340 176 and and CC cord-014597-66vd2mdu 2340 177 glucose glucose NN cord-014597-66vd2mdu 2340 178 concentration concentration NN cord-014597-66vd2mdu 2340 179 Continuous Continuous NNP cord-014597-66vd2mdu 2340 180 bioprocessing bioprocessing NN cord-014597-66vd2mdu 2340 181 : : : cord-014597-66vd2mdu 2340 182 The the DT cord-014597-66vd2mdu 2340 183 real real JJ cord-014597-66vd2mdu 2340 184 thing thing NN cord-014597-66vd2mdu 2340 185 this this DT cord-014597-66vd2mdu 2340 186 time time NN cord-014597-66vd2mdu 2340 187 ? ? . cord-014597-66vd2mdu 2341 1 mAbs mAbs NNP cord-014597-66vd2mdu 2341 2 White white JJ cord-014597-66vd2mdu 2341 3 paper paper NN cord-014597-66vd2mdu 2341 4 on on IN cord-014597-66vd2mdu 2341 5 continuous continuous JJ cord-014597-66vd2mdu 2341 6 bioprocessing bioprocesse VBG cord-014597-66vd2mdu 2341 7 FDA FDA NNP cord-014597-66vd2mdu 2341 8 Perspective Perspective NNP cord-014597-66vd2mdu 2341 9 on on IN cord-014597-66vd2mdu 2341 10 Continuous Continuous NNP cord-014597-66vd2mdu 2341 11 Manufacturing Manufacturing NNP cord-014597-66vd2mdu 2341 12 . . . cord-014597-66vd2mdu 2342 1 IFPAC IFPAC NNP cord-014597-66vd2mdu 2342 2 Annu Annu NNP cord-014597-66vd2mdu 2342 3 . . . cord-014597-66vd2mdu 2343 1 Meet meet VB cord-014597-66vd2mdu 2343 2 Screening Screening NNP cord-014597-66vd2mdu 2343 3 and and CC cord-014597-66vd2mdu 2343 4 Assessment Assessment NNP cord-014597-66vd2mdu 2343 5 of of IN cord-014597-66vd2mdu 2343 6 Performance Performance NNP cord-014597-66vd2mdu 2343 7 and and CC cord-014597-66vd2mdu 2343 8 Molecule Molecule NNP cord-014597-66vd2mdu 2343 9 Quality Quality NNP cord-014597-66vd2mdu 2343 10 Attributes Attributes NNPS cord-014597-66vd2mdu 2343 11 of of IN cord-014597-66vd2mdu 2343 12 Industrial Industrial NNP cord-014597-66vd2mdu 2343 13 Cell Cell NNP cord-014597-66vd2mdu 2343 14 Lines line NNS cord-014597-66vd2mdu 2343 15 across across IN cord-014597-66vd2mdu 2343 16 Different different JJ cord-014597-66vd2mdu 2343 17 Fed Fed NNP cord-014597-66vd2mdu 2343 18 - - HYPH cord-014597-66vd2mdu 2343 19 Batch Batch NNP cord-014597-66vd2mdu 2343 20 Systems Systems NNPS cord-014597-66vd2mdu 2343 21 Amanullah Amanullah NNP cord-014597-66vd2mdu 2343 22 : : : cord-014597-66vd2mdu 2344 1 Quantitative quantitative JJ cord-014597-66vd2mdu 2344 2 modeling modeling NN cord-014597-66vd2mdu 2344 3 of of IN cord-014597-66vd2mdu 2344 4 viable viable JJ cord-014597-66vd2mdu 2344 5 cell cell NN cord-014597-66vd2mdu 2344 6 density density NN cord-014597-66vd2mdu 2344 7 , , , cord-014597-66vd2mdu 2344 8 cell cell NN cord-014597-66vd2mdu 2344 9 size size NN cord-014597-66vd2mdu 2344 10 , , , cord-014597-66vd2mdu 2344 11 intracellular intracellular JJ cord-014597-66vd2mdu 2344 12 conductivity conductivity NN cord-014597-66vd2mdu 2344 13 , , , cord-014597-66vd2mdu 2344 14 and and CC cord-014597-66vd2mdu 2344 15 membrane membrane NN cord-014597-66vd2mdu 2344 16 capacitance capacitance NN cord-014597-66vd2mdu 2344 17 in in IN cord-014597-66vd2mdu 2344 18 batch batch NN cord-014597-66vd2mdu 2344 19 and and CC cord-014597-66vd2mdu 2344 20 fed fed JJ cord-014597-66vd2mdu 2344 21 - - HYPH cord-014597-66vd2mdu 2344 22 batch batch NN cord-014597-66vd2mdu 2344 23 CHO CHO NNP cord-014597-66vd2mdu 2344 24 processes process NNS cord-014597-66vd2mdu 2344 25 using use VBG cord-014597-66vd2mdu 2344 26 dielectric dielectric NN cord-014597-66vd2mdu 2344 27 spectroscopy spectroscopy NN cord-014597-66vd2mdu 2344 28 Optimal Optimal NNP cord-014597-66vd2mdu 2344 29 and and CC cord-014597-66vd2mdu 2344 30 consistent consistent JJ cord-014597-66vd2mdu 2344 31 protein protein NN cord-014597-66vd2mdu 2344 32 glycosylation glycosylation NN cord-014597-66vd2mdu 2344 33 in in IN cord-014597-66vd2mdu 2344 34 mammcalian mammcalian JJ cord-014597-66vd2mdu 2344 35 cell cell NN cord-014597-66vd2mdu 2344 36 culture culture NN cord-014597-66vd2mdu 2344 37 Journal Journal NNP cord-014597-66vd2mdu 2344 38 of of IN cord-014597-66vd2mdu 2344 39 laboratory laboratory NNP cord-014597-66vd2mdu 2344 40 automation automation NN cord-014597-66vd2mdu 2344 41 . . . cord-014597-66vd2mdu 2345 1 Designs design NNS cord-014597-66vd2mdu 2345 2 and and CC cord-014597-66vd2mdu 2345 3 Concept Concept NNP cord-014597-66vd2mdu 2345 4 - - HYPH cord-014597-66vd2mdu 2345 5 Reliance Reliance NNP cord-014597-66vd2mdu 2345 6 of of IN cord-014597-66vd2mdu 2345 7 a a DT cord-014597-66vd2mdu 2345 8 Fully fully RB cord-014597-66vd2mdu 2345 9 Automated Automated NNP cord-014597-66vd2mdu 2345 10 High High NNP cord-014597-66vd2mdu 2345 11 Content Content NNP cord-014597-66vd2mdu 2345 12 Screening Screening NNP cord-014597-66vd2mdu 2345 13 Platform Platform NNP cord-014597-66vd2mdu 2345 14 Mini Mini NNP cord-014597-66vd2mdu 2345 15 - - HYPH cord-014597-66vd2mdu 2345 16 bioreactor bioreactor NN cord-014597-66vd2mdu 2345 17 as as IN cord-014597-66vd2mdu 2345 18 a a DT cord-014597-66vd2mdu 2345 19 highthroughput highthroughput NN cord-014597-66vd2mdu 2345 20 tool tool NN cord-014597-66vd2mdu 2345 21 for for IN cord-014597-66vd2mdu 2345 22 culture culture NN cord-014597-66vd2mdu 2345 23 process process NN cord-014597-66vd2mdu 2345 24 development development NN cord-014597-66vd2mdu 2345 25 to to TO cord-014597-66vd2mdu 2345 26 accelerate accelerate VB cord-014597-66vd2mdu 2345 27 transfer transfer NN cord-014597-66vd2mdu 2345 28 to to IN cord-014597-66vd2mdu 2345 29 stainless stainless JJ cord-014597-66vd2mdu 2345 30 steel steel NN cord-014597-66vd2mdu 2345 31 manufacturing manufacturing NN cord-014597-66vd2mdu 2345 32 scale scale NN cord-014597-66vd2mdu 2345 33 : : : cord-014597-66vd2mdu 2345 34 comparability comparability NN cord-014597-66vd2mdu 2345 35 study study NN cord-014597-66vd2mdu 2345 36 from from IN cord-014597-66vd2mdu 2345 37 process process NN cord-014597-66vd2mdu 2345 38 performance performance NN cord-014597-66vd2mdu 2345 39 to to TO cord-014597-66vd2mdu 2345 40 product product NN cord-014597-66vd2mdu 2345 41 quality quality NN cord-014597-66vd2mdu 2345 42 attributes attribute VBZ cord-014597-66vd2mdu 2345 43 Perfusion perfusion NN cord-014597-66vd2mdu 2345 44 media medium NNS cord-014597-66vd2mdu 2345 45 development development NN cord-014597-66vd2mdu 2345 46 using use VBG cord-014597-66vd2mdu 2345 47 cell cell NN cord-014597-66vd2mdu 2345 48 settling settle VBG cord-014597-66vd2mdu 2345 49 in in IN cord-014597-66vd2mdu 2345 50 automated automated JJ cord-014597-66vd2mdu 2345 51 cell cell NN cord-014597-66vd2mdu 2345 52 culture culture NN cord-014597-66vd2mdu 2345 53 system system NN cord-014597-66vd2mdu 2345 54 Model model NN cord-014597-66vd2mdu 2345 55 - - HYPH cord-014597-66vd2mdu 2345 56 based base VBN cord-014597-66vd2mdu 2345 57 Design Design NNP cord-014597-66vd2mdu 2345 58 of of IN cord-014597-66vd2mdu 2345 59 Process Process NNP cord-014597-66vd2mdu 2345 60 Strategies Strategies NNPS cord-014597-66vd2mdu 2345 61 for for IN cord-014597-66vd2mdu 2345 62 Cell cell NN cord-014597-66vd2mdu 2345 63 Culture culture NN cord-014597-66vd2mdu 2345 64 Bioprocesses Bioprocesses NNP cord-014597-66vd2mdu 2345 65 : : : cord-014597-66vd2mdu 2345 66 State state NN cord-014597-66vd2mdu 2345 67 of of IN cord-014597-66vd2mdu 2345 68 the the DT cord-014597-66vd2mdu 2345 69 Art Art NNP cord-014597-66vd2mdu 2345 70 and and CC cord-014597-66vd2mdu 2345 71 New New NNP cord-014597-66vd2mdu 2345 72 Perspectives Perspectives NNPS cord-014597-66vd2mdu 2345 73 Model Model NNP cord-014597-66vd2mdu 2345 74 - - HYPH cord-014597-66vd2mdu 2345 75 based base VBN cord-014597-66vd2mdu 2345 76 strategy strategy NN cord-014597-66vd2mdu 2345 77 for for IN cord-014597-66vd2mdu 2345 78 cell cell NN cord-014597-66vd2mdu 2345 79 culture culture NN cord-014597-66vd2mdu 2345 80 seed seed NN cord-014597-66vd2mdu 2345 81 train train NN cord-014597-66vd2mdu 2345 82 layout layout NN cord-014597-66vd2mdu 2345 83 verified verify VBN cord-014597-66vd2mdu 2345 84 at at IN cord-014597-66vd2mdu 2345 85 lab lab NN cord-014597-66vd2mdu 2345 86 scale scale NN cord-014597-66vd2mdu 2346 1 Hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 2346 2 stimulus stimulus NN cord-014597-66vd2mdu 2346 3 study study NN cord-014597-66vd2mdu 2346 4 discloses disclose VBZ cord-014597-66vd2mdu 2346 5 benefits benefit NNS cord-014597-66vd2mdu 2346 6 in in IN cord-014597-66vd2mdu 2346 7 ATP ATP NNP cord-014597-66vd2mdu 2346 8 supply supply NN cord-014597-66vd2mdu 2346 9 and and CC cord-014597-66vd2mdu 2346 10 reveals reveal VBZ cord-014597-66vd2mdu 2346 11 miRNA miRNA NNP cord-014597-66vd2mdu 2346 12 / / SYM cord-014597-66vd2mdu 2346 13 mRNA mRNA NNP cord-014597-66vd2mdu 2346 14 targets target VBZ cord-014597-66vd2mdu 2346 15 to to TO cord-014597-66vd2mdu 2346 16 improve improve VB cord-014597-66vd2mdu 2346 17 recombinant recombinant JJ cord-014597-66vd2mdu 2346 18 protein protein NN cord-014597-66vd2mdu 2346 19 production production NN cord-014597-66vd2mdu 2346 20 of of IN cord-014597-66vd2mdu 2346 21 CHO CHO NNP cord-014597-66vd2mdu 2346 22 cells cell NNS cord-014597-66vd2mdu 2346 23 Effects effect NNS cord-014597-66vd2mdu 2346 24 of of IN cord-014597-66vd2mdu 2346 25 osmoprotectant osmoprotectant JJ cord-014597-66vd2mdu 2346 26 compounds compound NNS cord-014597-66vd2mdu 2346 27 on on IN cord-014597-66vd2mdu 2346 28 NCAM NCAM NNP cord-014597-66vd2mdu 2346 29 polysialylation polysialylation NN cord-014597-66vd2mdu 2346 30 under under IN cord-014597-66vd2mdu 2346 31 hyperosmotic hyperosmotic JJ cord-014597-66vd2mdu 2346 32 stress stress NN cord-014597-66vd2mdu 2346 33 and and CC cord-014597-66vd2mdu 2346 34 elevated elevate VBN cord-014597-66vd2mdu 2346 35 pCO pco CD cord-014597-66vd2mdu 2346 36 2 2 CD cord-014597-66vd2mdu 2346 37 Evaluating evaluate VBG cord-014597-66vd2mdu 2346 38 the the DT cord-014597-66vd2mdu 2346 39 bottlenecks bottleneck NNS cord-014597-66vd2mdu 2346 40 of of IN cord-014597-66vd2mdu 2346 41 recombinant recombinant JJ cord-014597-66vd2mdu 2346 42 IgM IgM NNP cord-014597-66vd2mdu 2346 43 production production NN cord-014597-66vd2mdu 2346 44 in in IN cord-014597-66vd2mdu 2346 45 mammalian mammalian JJ cord-014597-66vd2mdu 2346 46 cells cell NNS cord-014597-66vd2mdu 2346 47 IgM IgM NNP cord-014597-66vd2mdu 2346 48 characterization characterization NN cord-014597-66vd2mdu 2346 49 directly directly RB cord-014597-66vd2mdu 2346 50 performed perform VBN cord-014597-66vd2mdu 2346 51 in in IN cord-014597-66vd2mdu 2346 52 crude crude JJ cord-014597-66vd2mdu 2346 53 culture culture NN cord-014597-66vd2mdu 2346 54 supernatants supernatant NNS cord-014597-66vd2mdu 2346 55 by by IN cord-014597-66vd2mdu 2346 56 a a DT cord-014597-66vd2mdu 2346 57 new new JJ cord-014597-66vd2mdu 2346 58 simple simple JJ cord-014597-66vd2mdu 2346 59 electrophoretic electrophoretic JJ cord-014597-66vd2mdu 2346 60 method method NN cord-014597-66vd2mdu 2346 61 Effect effect NN cord-014597-66vd2mdu 2346 62 of of IN cord-014597-66vd2mdu 2346 63 culture culture NN cord-014597-66vd2mdu 2347 1 pH pH NNP cord-014597-66vd2mdu 2347 2 on on IN cord-014597-66vd2mdu 2347 3 erythropoietin erythropoietin NN cord-014597-66vd2mdu 2347 4 production production NN cord-014597-66vd2mdu 2347 5 by by IN cord-014597-66vd2mdu 2347 6 Chinese chinese JJ cord-014597-66vd2mdu 2347 7 hamster hamster NN cord-014597-66vd2mdu 2347 8 ovary ovary NN cord-014597-66vd2mdu 2347 9 cells cell NNS cord-014597-66vd2mdu 2347 10 grown grow VBN cord-014597-66vd2mdu 2347 11 in in IN cord-014597-66vd2mdu 2347 12 suspension suspension NN cord-014597-66vd2mdu 2347 13 at at IN cord-014597-66vd2mdu 2347 14 32.5 32.5 CD cord-014597-66vd2mdu 2347 15 and and CC cord-014597-66vd2mdu 2347 16 37.0 37.0 CD cord-014597-66vd2mdu 2347 17 ° ° NN cord-014597-66vd2mdu 2347 18 C C NNP cord-014597-66vd2mdu 2347 19 Enhancing Enhancing NNP cord-014597-66vd2mdu 2347 20 Protein Protein NNP cord-014597-66vd2mdu 2347 21 Expression Expression NNP cord-014597-66vd2mdu 2347 22 in in IN cord-014597-66vd2mdu 2347 23 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 2347 24 Cells cell NNS cord-014597-66vd2mdu 2347 25 by by IN cord-014597-66vd2mdu 2347 26 Lowering lower VBG cord-014597-66vd2mdu 2347 27 Culture culture NN cord-014597-66vd2mdu 2347 28 Temperature temperature NN cord-014597-66vd2mdu 2347 29 Relationship relationship NN cord-014597-66vd2mdu 2347 30 between between IN cord-014597-66vd2mdu 2347 31 tissue tissue NN cord-014597-66vd2mdu 2347 32 plasminogen plasminogen NN cord-014597-66vd2mdu 2347 33 activator activator NN cord-014597-66vd2mdu 2347 34 production production NN cord-014597-66vd2mdu 2347 35 and and CC cord-014597-66vd2mdu 2347 36 specific specific JJ cord-014597-66vd2mdu 2347 37 growth growth NN cord-014597-66vd2mdu 2347 38 rate rate NN cord-014597-66vd2mdu 2347 39 in in IN cord-014597-66vd2mdu 2347 40 Chinese chinese JJ cord-014597-66vd2mdu 2347 41 Hamster Hamster NNP cord-014597-66vd2mdu 2347 42 Ovary Ovary NNP cord-014597-66vd2mdu 2347 43 cells cell NNS cord-014597-66vd2mdu 2347 44 cultured culture VBN cord-014597-66vd2mdu 2347 45 in in IN cord-014597-66vd2mdu 2347 46 mannose mannose NN cord-014597-66vd2mdu 2347 47 at at IN cord-014597-66vd2mdu 2347 48 low low JJ cord-014597-66vd2mdu 2347 49 temperature temperature NN cord-014597-66vd2mdu 2348 1 A a DT cord-014597-66vd2mdu 2348 2 quantitative quantitative JJ cord-014597-66vd2mdu 2348 3 proteomic proteomic JJ cord-014597-66vd2mdu 2348 4 analysis analysis NN cord-014597-66vd2mdu 2348 5 of of IN cord-014597-66vd2mdu 2348 6 cellular cellular JJ cord-014597-66vd2mdu 2348 7 responses response NNS cord-014597-66vd2mdu 2348 8 to to IN cord-014597-66vd2mdu 2348 9 high high JJ cord-014597-66vd2mdu 2348 10 glucose glucose NN cord-014597-66vd2mdu 2348 11 media medium NNS cord-014597-66vd2mdu 2348 12 in in IN cord-014597-66vd2mdu 2348 13 Chinese chinese JJ cord-014597-66vd2mdu 2348 14 hamster hamster NN cord-014597-66vd2mdu 2348 15 ovary ovary NN cord-014597-66vd2mdu 2348 16 cells cell NNS cord-014597-66vd2mdu 2349 1 Process process NN cord-014597-66vd2mdu 2349 2 analytical analytical JJ cord-014597-66vd2mdu 2349 3 technologies technology NNS cord-014597-66vd2mdu 2349 4 in in IN cord-014597-66vd2mdu 2349 5 the the DT cord-014597-66vd2mdu 2349 6 pharmaceutical pharmaceutical NN cord-014597-66vd2mdu 2349 7 industry industry NN cord-014597-66vd2mdu 2349 8 : : : cord-014597-66vd2mdu 2349 9 the the DT cord-014597-66vd2mdu 2349 10 FDA FDA NNP cord-014597-66vd2mdu 2349 11 's 's POS cord-014597-66vd2mdu 2349 12 PAT PAT NNP cord-014597-66vd2mdu 2349 13 initiative initiative NN cord-014597-66vd2mdu 2349 14 Effects effect NNS cord-014597-66vd2mdu 2349 15 of of IN cord-014597-66vd2mdu 2349 16 ammonium ammonium NN cord-014597-66vd2mdu 2349 17 and and CC cord-014597-66vd2mdu 2349 18 lactate lactate NN cord-014597-66vd2mdu 2349 19 on on IN cord-014597-66vd2mdu 2349 20 growth growth NN cord-014597-66vd2mdu 2349 21 and and CC cord-014597-66vd2mdu 2349 22 metabolism metabolism NN cord-014597-66vd2mdu 2349 23 of of IN cord-014597-66vd2mdu 2349 24 a a DT cord-014597-66vd2mdu 2349 25 recombinant recombinant JJ cord-014597-66vd2mdu 2349 26 Chinese chinese JJ cord-014597-66vd2mdu 2349 27 hamster hamster NN cord-014597-66vd2mdu 2349 28 ovary ovary NN cord-014597-66vd2mdu 2349 29 cell cell NN cord-014597-66vd2mdu 2349 30 culture culture NN cord-014597-66vd2mdu 2349 31 Glycosylation Glycosylation NNP cord-014597-66vd2mdu 2349 32 in in IN cord-014597-66vd2mdu 2349 33 Cell Cell NNP cord-014597-66vd2mdu 2349 34 Culture Culture NNP cord-014597-66vd2mdu 2349 35 Structural structural JJ cord-014597-66vd2mdu 2349 36 mechanism mechanism NN cord-014597-66vd2mdu 2349 37 of of IN cord-014597-66vd2mdu 2349 38 high high JJ cord-014597-66vd2mdu 2349 39 affinity affinity NN cord-014597-66vd2mdu 2349 40 FcgammaRI FcgammaRI NNP cord-014597-66vd2mdu 2349 41 recognition recognition NN cord-014597-66vd2mdu 2349 42 of of IN cord-014597-66vd2mdu 2349 43 immunoglobulin immunoglobulin NN cord-014597-66vd2mdu 2349 44 G G NNP cord-014597-66vd2mdu 2349 45 Inhibition inhibition NN cord-014597-66vd2mdu 2349 46 of of IN cord-014597-66vd2mdu 2349 47 glycosylation glycosylation NN cord-014597-66vd2mdu 2349 48 on on IN cord-014597-66vd2mdu 2349 49 a a DT cord-014597-66vd2mdu 2349 50 camelid camelid NN cord-014597-66vd2mdu 2349 51 antibody antibody NN cord-014597-66vd2mdu 2349 52 uniquely uniquely RB cord-014597-66vd2mdu 2349 53 affects affect VBZ cord-014597-66vd2mdu 2349 54 its -PRON- PRP$ cord-014597-66vd2mdu 2349 55 FcγRI FcγRI NNP cord-014597-66vd2mdu 2349 56 binding bind VBG cord-014597-66vd2mdu 2349 57 activity activity NN cord-014597-66vd2mdu 2349 58 Investigation Investigation NNP cord-014597-66vd2mdu 2349 59 of of IN cord-014597-66vd2mdu 2349 60 CHO CHO NNP cord-014597-66vd2mdu 2349 61 Secretome Secretome NNP cord-014597-66vd2mdu 2349 62 : : : cord-014597-66vd2mdu 2349 63 Potential potential JJ cord-014597-66vd2mdu 2349 64 Way way NN cord-014597-66vd2mdu 2349 65 to to TO cord-014597-66vd2mdu 2349 66 Improve improve VB cord-014597-66vd2mdu 2349 67 Recombinant Recombinant NNP cord-014597-66vd2mdu 2349 68 Protein Protein NNP cord-014597-66vd2mdu 2349 69 Production Production NNP cord-014597-66vd2mdu 2349 70 from from IN cord-014597-66vd2mdu 2349 71 Bioprocess Bioprocess NNP cord-014597-66vd2mdu 2349 72 Bladder Bladder NNP cord-014597-66vd2mdu 2349 73 cancer cancer NN cord-014597-66vd2mdu 2350 1 cell cell NN cord-014597-66vd2mdu 2350 2 - - HYPH cord-014597-66vd2mdu 2350 3 derived derive VBN cord-014597-66vd2mdu 2350 4 exosomes exosome NNS cord-014597-66vd2mdu 2350 5 inhibit inhibit NN cord-014597-66vd2mdu 2350 6 tumor tumor NN cord-014597-66vd2mdu 2350 7 cell cell NN cord-014597-66vd2mdu 2350 8 apoptosis apoptosis NN cord-014597-66vd2mdu 2350 9 and and CC cord-014597-66vd2mdu 2350 10 induce induce VB cord-014597-66vd2mdu 2350 11 cell cell NN cord-014597-66vd2mdu 2350 12 proliferation proliferation NN cord-014597-66vd2mdu 2350 13 in in IN cord-014597-66vd2mdu 2350 14 vitro vitro FW cord-014597-66vd2mdu 2350 15 Exploring explore VBG cord-014597-66vd2mdu 2350 16 Packaged package VBN cord-014597-66vd2mdu 2350 17 Microvesicle Microvesicle NNP cord-014597-66vd2mdu 2350 18 Proteome Proteome NNP cord-014597-66vd2mdu 2350 19 Composition Composition NNP cord-014597-66vd2mdu 2350 20 of of IN cord-014597-66vd2mdu 2350 21 Chinese chinese JJ cord-014597-66vd2mdu 2350 22 Hamster Hamster NNP cord-014597-66vd2mdu 2350 23 Ovary Ovary NNP cord-014597-66vd2mdu 2350 24 Secretome Secretome NNP cord-014597-66vd2mdu 2350 25 Glycome Glycome NNP cord-014597-66vd2mdu 2350 26 mapping mapping NN cord-014597-66vd2mdu 2350 27 on on IN cord-014597-66vd2mdu 2350 28 DNA dna NN cord-014597-66vd2mdu 2350 29 sequencing sequencing NN cord-014597-66vd2mdu 2350 30 equipment equipment NN cord-014597-66vd2mdu 2350 31 Iron iron NN cord-014597-66vd2mdu 2350 32 ( ( -LRB- cord-014597-66vd2mdu 2350 33 III III NNP cord-014597-66vd2mdu 2350 34 ) ) -RRB- cord-014597-66vd2mdu 2351 1 citrate citrate NNP cord-014597-66vd2mdu 2351 2 inhibits inhibit VBZ cord-014597-66vd2mdu 2351 3 polyethylenimine polyethylenimine NNP cord-014597-66vd2mdu 2351 4 - - HYPH cord-014597-66vd2mdu 2351 5 mediated mediate VBN cord-014597-66vd2mdu 2351 6 transient transient JJ cord-014597-66vd2mdu 2351 7 transfection transfection NN cord-014597-66vd2mdu 2351 8 of of IN cord-014597-66vd2mdu 2351 9 Chinese chinese JJ cord-014597-66vd2mdu 2351 10 hamster hamster NN cord-014597-66vd2mdu 2351 11 ovary ovary NN cord-014597-66vd2mdu 2351 12 cells cell NNS cord-014597-66vd2mdu 2351 13 in in IN cord-014597-66vd2mdu 2351 14 serum serum NN cord-014597-66vd2mdu 2351 15 - - HYPH cord-014597-66vd2mdu 2351 16 free free JJ cord-014597-66vd2mdu 2351 17 medium medium NN cord-014597-66vd2mdu 2351 18 Efficient efficient JJ cord-014597-66vd2mdu 2351 19 high high JJ cord-014597-66vd2mdu 2351 20 - - HYPH cord-014597-66vd2mdu 2351 21 throughput throughput NN cord-014597-66vd2mdu 2351 22 biological biological JJ cord-014597-66vd2mdu 2351 23 process process NN cord-014597-66vd2mdu 2351 24 characterization characterization NN cord-014597-66vd2mdu 2351 25 Scale scale NN cord-014597-66vd2mdu 2351 26 - - HYPH cord-014597-66vd2mdu 2351 27 up up NN cord-014597-66vd2mdu 2351 28 of of IN cord-014597-66vd2mdu 2351 29 a a DT cord-014597-66vd2mdu 2351 30 stirred stir VBN cord-014597-66vd2mdu 2351 31 single single JJ cord-014597-66vd2mdu 2351 32 - - HYPH cord-014597-66vd2mdu 2351 33 use use NN cord-014597-66vd2mdu 2351 34 bioreactor bioreactor NN cord-014597-66vd2mdu 2351 35 family family NN cord-014597-66vd2mdu 2351 36 Quality quality NN cord-014597-66vd2mdu 2351 37 control control NN cord-014597-66vd2mdu 2351 38 : : : cord-014597-66vd2mdu 2351 39 ER er NN cord-014597-66vd2mdu 2351 40 - - HYPH cord-014597-66vd2mdu 2351 41 associated associate VBN cord-014597-66vd2mdu 2351 42 degradation degradation NN cord-014597-66vd2mdu 2351 43 : : : cord-014597-66vd2mdu 2351 44 protein protein NN cord-014597-66vd2mdu 2351 45 quality quality NN cord-014597-66vd2mdu 2351 46 control control NN cord-014597-66vd2mdu 2351 47 and and CC cord-014597-66vd2mdu 2351 48 beyond beyond IN cord-014597-66vd2mdu 2352 1 Pharmacological pharmacological JJ cord-014597-66vd2mdu 2352 2 targeting targeting NN cord-014597-66vd2mdu 2352 3 of of IN cord-014597-66vd2mdu 2352 4 endoplasmic endoplasmic NN cord-014597-66vd2mdu 2352 5 reticulum reticulum NN cord-014597-66vd2mdu 2352 6 stress stress NN cord-014597-66vd2mdu 2352 7 signaling signal VBG cord-014597-66vd2mdu 2352 8 in in IN cord-014597-66vd2mdu 2352 9 cancer cancer NN cord-014597-66vd2mdu 2352 10 When when WRB cord-014597-66vd2mdu 2352 11 ER ER NNP cord-014597-66vd2mdu 2352 12 stress stress NN cord-014597-66vd2mdu 2352 13 reaches reach VBZ cord-014597-66vd2mdu 2352 14 a a DT cord-014597-66vd2mdu 2352 15 dead dead JJ cord-014597-66vd2mdu 2352 16 end end NN cord-014597-66vd2mdu 2352 17 Oxidative oxidative JJ cord-014597-66vd2mdu 2352 18 stress stress NN cord-014597-66vd2mdu 2352 19 and and CC cord-014597-66vd2mdu 2352 20 antioxidant antioxidant NN cord-014597-66vd2mdu 2352 21 defense defense NN cord-014597-66vd2mdu 2353 1 The the DT cord-014597-66vd2mdu 2353 2 antioxidant antioxidant JJ cord-014597-66vd2mdu 2353 3 edaravone edaravone NN cord-014597-66vd2mdu 2353 4 attenuates attenuate VBZ cord-014597-66vd2mdu 2353 5 ER er NN cord-014597-66vd2mdu 2353 6 - - HYPH cord-014597-66vd2mdu 2353 7 stress stress NN cord-014597-66vd2mdu 2353 8 - - HYPH cord-014597-66vd2mdu 2353 9 mediated mediate VBN cord-014597-66vd2mdu 2353 10 cardiac cardiac JJ cord-014597-66vd2mdu 2353 11 apoptosis apoptosis NN cord-014597-66vd2mdu 2353 12 and and CC cord-014597-66vd2mdu 2353 13 dysfunction dysfunction NN cord-014597-66vd2mdu 2353 14 in in IN cord-014597-66vd2mdu 2353 15 rats rat NNS cord-014597-66vd2mdu 2353 16 with with IN cord-014597-66vd2mdu 2353 17 autoimmune autoimmune JJ cord-014597-66vd2mdu 2353 18 myocarditis myocarditis NN cord-014597-66vd2mdu 2353 19 Advanced Advanced NNP cord-014597-66vd2mdu 2353 20 Process Process NNP cord-014597-66vd2mdu 2353 21 and and CC cord-014597-66vd2mdu 2353 22 Control Control NNP cord-014597-66vd2mdu 2353 23 Strategies Strategies NNPS cord-014597-66vd2mdu 2353 24 for for IN cord-014597-66vd2mdu 2353 25 Bioreactors bioreactor NNS cord-014597-66vd2mdu 2353 26 . . . cord-014597-66vd2mdu 2354 1 Book Book NNP cord-014597-66vd2mdu 2354 2 chapter chapter NN cord-014597-66vd2mdu 2354 3 Model Model NNP cord-014597-66vd2mdu 2354 4 - - HYPH cord-014597-66vd2mdu 2354 5 based base VBN cord-014597-66vd2mdu 2354 6 strategy strategy NN cord-014597-66vd2mdu 2354 7 for for IN cord-014597-66vd2mdu 2354 8 cell cell NN cord-014597-66vd2mdu 2354 9 culture culture NN cord-014597-66vd2mdu 2354 10 seed seed NN cord-014597-66vd2mdu 2354 11 train train NN cord-014597-66vd2mdu 2354 12 layout layout NN cord-014597-66vd2mdu 2354 13 verified verify VBN cord-014597-66vd2mdu 2354 14 at at IN cord-014597-66vd2mdu 2354 15 lab lab NN cord-014597-66vd2mdu 2354 16 scale scale NN cord-014597-66vd2mdu 2354 17 Seed seed NN cord-014597-66vd2mdu 2354 18 train train NN cord-014597-66vd2mdu 2354 19 optimization optimization NN cord-014597-66vd2mdu 2354 20 for for IN cord-014597-66vd2mdu 2354 21 cell cell NN cord-014597-66vd2mdu 2354 22 culture culture NN cord-014597-66vd2mdu 2354 23 . . . cord-014597-66vd2mdu 2355 1 Chapter chapter NN cord-014597-66vd2mdu 2355 2 High high JJ cord-014597-66vd2mdu 2355 3 Cell Cell NNP cord-014597-66vd2mdu 2355 4 Density density NN cord-014597-66vd2mdu 2355 5 Cultivation Cultivation NNP cord-014597-66vd2mdu 2355 6 of of IN cord-014597-66vd2mdu 2355 7 Human Human NNP cord-014597-66vd2mdu 2355 8 Leukemia Leukemia NNP cord-014597-66vd2mdu 2355 9 T T NNP cord-014597-66vd2mdu 2355 10 Cells cell NNS cord-014597-66vd2mdu 2355 11 ( ( -LRB- cord-014597-66vd2mdu 2355 12 Jurkat Jurkat NNP cord-014597-66vd2mdu 2355 13 Cells Cells NNP cord-014597-66vd2mdu 2355 14 ) ) -RRB- cord-014597-66vd2mdu 2355 15 in in IN cord-014597-66vd2mdu 2355 16 Semipermeable Semipermeable NNP cord-014597-66vd2mdu 2355 17 Polyelectrolyte Polyelectrolyte NNP cord-014597-66vd2mdu 2355 18 Microcapsules Microcapsules NNP cord-014597-66vd2mdu 2355 19 . . . cord-014597-66vd2mdu 2356 1 Eng Eng NNP cord-014597-66vd2mdu 2356 2 . . . cord-014597-66vd2mdu 2357 1 Life Life NNP cord-014597-66vd2mdu 2357 2 Sci Sci NNP cord-014597-66vd2mdu 2357 3 Cell Cell NNP cord-014597-66vd2mdu 2357 4 retention retention NN cord-014597-66vd2mdu 2357 5 by by IN cord-014597-66vd2mdu 2357 6 encapsulation encapsulation NN cord-014597-66vd2mdu 2357 7 for for IN cord-014597-66vd2mdu 2357 8 the the DT cord-014597-66vd2mdu 2357 9 cultivation cultivation NN cord-014597-66vd2mdu 2357 10 of of IN cord-014597-66vd2mdu 2357 11 Jurkat Jurkat NNP cord-014597-66vd2mdu 2357 12 cells cell NNS cord-014597-66vd2mdu 2357 13 in in IN cord-014597-66vd2mdu 2357 14 fixed fix VBN cord-014597-66vd2mdu 2357 15 and and CC cord-014597-66vd2mdu 2357 16 fluidized fluidized JJ cord-014597-66vd2mdu 2357 17 bed bed NN cord-014597-66vd2mdu 2357 18 reactors reactor NNS cord-014597-66vd2mdu 2358 1 The the DT cord-014597-66vd2mdu 2358 2 role role NN cord-014597-66vd2mdu 2358 3 of of IN cord-014597-66vd2mdu 2358 4 interleukin-2 interleukin-2 NN cord-014597-66vd2mdu 2358 5 during during IN cord-014597-66vd2mdu 2358 6 homeostasis homeostasis NN cord-014597-66vd2mdu 2358 7 and and CC cord-014597-66vd2mdu 2358 8 activation activation NN cord-014597-66vd2mdu 2358 9 of of IN cord-014597-66vd2mdu 2358 10 the the DT cord-014597-66vd2mdu 2358 11 immune immune JJ cord-014597-66vd2mdu 2358 12 system system NN cord-014597-66vd2mdu 2358 13 Creating create VBG cord-014597-66vd2mdu 2358 14 a a DT cord-014597-66vd2mdu 2358 15 Biomimetic Biomimetic NNP cord-014597-66vd2mdu 2358 16 Microenvironment Microenvironment NNP cord-014597-66vd2mdu 2358 17 for for IN cord-014597-66vd2mdu 2358 18 the the DT cord-014597-66vd2mdu 2358 19 Ex Ex NNP cord-014597-66vd2mdu 2358 20 Vivo Vivo NNP cord-014597-66vd2mdu 2358 21 Expansion Expansion NNP cord-014597-66vd2mdu 2358 22 of of IN cord-014597-66vd2mdu 2358 23 Primary Primary NNP cord-014597-66vd2mdu 2358 24 Human Human NNP cord-014597-66vd2mdu 2359 1 The the DT cord-014597-66vd2mdu 2359 2 Era Era NNP cord-014597-66vd2mdu 2359 3 of of IN cord-014597-66vd2mdu 2359 4 Digital Digital NNP cord-014597-66vd2mdu 2359 5 Biomanufacturing Biomanufacturing NNP cord-014597-66vd2mdu 2360 1 The the DT cord-014597-66vd2mdu 2360 2 Multivariate Multivariate NNP cord-014597-66vd2mdu 2360 3 Normal normal JJ cord-014597-66vd2mdu 2360 4 Distribution distribution NN cord-014597-66vd2mdu 2360 5 Recovery Recovery NNP cord-014597-66vd2mdu 2360 6 from from IN cord-014597-66vd2mdu 2360 7 rabies rabies NN cord-014597-66vd2mdu 2360 8 : : : cord-014597-66vd2mdu 2361 1 A a DT cord-014597-66vd2mdu 2361 2 call call NN cord-014597-66vd2mdu 2361 3 to to IN cord-014597-66vd2mdu 2361 4 arms arm NNS cord-014597-66vd2mdu 2362 1 The the DT cord-014597-66vd2mdu 2362 2 role role NN cord-014597-66vd2mdu 2362 3 of of IN cord-014597-66vd2mdu 2362 4 vaccination vaccination NN cord-014597-66vd2mdu 2362 5 in in IN cord-014597-66vd2mdu 2362 6 rabies rabies NN cord-014597-66vd2mdu 2362 7 prevention prevention NN cord-014597-66vd2mdu 2363 1 Eliminating eliminate VBG cord-014597-66vd2mdu 2363 2 canine canine JJ cord-014597-66vd2mdu 2363 3 rabies rabie NNS cord-014597-66vd2mdu 2363 4 , , , cord-014597-66vd2mdu 2363 5 the the DT cord-014597-66vd2mdu 2363 6 principal principal JJ cord-014597-66vd2mdu 2363 7 source source NN cord-014597-66vd2mdu 2363 8 of of IN cord-014597-66vd2mdu 2363 9 human human JJ cord-014597-66vd2mdu 2363 10 infection infection NN cord-014597-66vd2mdu 2363 11 : : : cord-014597-66vd2mdu 2363 12 What what WP cord-014597-66vd2mdu 2363 13 will will MD cord-014597-66vd2mdu 2363 14 it -PRON- PRP cord-014597-66vd2mdu 2363 15 take take VB cord-014597-66vd2mdu 2363 16 ? ? . cord-014597-66vd2mdu 2364 1 Rabies rabies NN cord-014597-66vd2mdu 2364 2 virus virus NN cord-014597-66vd2mdu 2364 3 - - HYPH cord-014597-66vd2mdu 2364 4 like like JJ cord-014597-66vd2mdu 2364 5 particles particle NNS cord-014597-66vd2mdu 2364 6 expressed express VBN cord-014597-66vd2mdu 2364 7 in in IN cord-014597-66vd2mdu 2364 8 HEK293 HEK293 NNP cord-014597-66vd2mdu 2364 9 cells cell NNS cord-014597-66vd2mdu 2364 10 Immunogenic immunogenic JJ cord-014597-66vd2mdu 2364 11 virus virus NN cord-014597-66vd2mdu 2364 12 - - HYPH cord-014597-66vd2mdu 2364 13 like like JJ cord-014597-66vd2mdu 2364 14 particles particle NNS cord-014597-66vd2mdu 2364 15 continuously continuously RB cord-014597-66vd2mdu 2364 16 expressed express VBN cord-014597-66vd2mdu 2364 17 in in IN cord-014597-66vd2mdu 2364 18 mammalian mammalian JJ cord-014597-66vd2mdu 2364 19 cells cell NNS cord-014597-66vd2mdu 2364 20 as as IN cord-014597-66vd2mdu 2364 21 a a DT cord-014597-66vd2mdu 2364 22 veterinary veterinary JJ cord-014597-66vd2mdu 2364 23 rabies rabies NN cord-014597-66vd2mdu 2364 24 vaccine vaccine NN cord-014597-66vd2mdu 2364 25 candidate candidate NN cord-014597-66vd2mdu 2364 26 An an DT cord-014597-66vd2mdu 2364 27 avian avian JJ cord-014597-66vd2mdu 2364 28 cell cell NN cord-014597-66vd2mdu 2364 29 line line NN cord-014597-66vd2mdu 2364 30 designed design VBN cord-014597-66vd2mdu 2364 31 for for IN cord-014597-66vd2mdu 2364 32 production production NN cord-014597-66vd2mdu 2364 33 of of IN cord-014597-66vd2mdu 2364 34 highly highly RB cord-014597-66vd2mdu 2364 35 attenuated attenuated JJ cord-014597-66vd2mdu 2364 36 viruses virus NNS cord-014597-66vd2mdu 2364 37 A a DT cord-014597-66vd2mdu 2364 38 chemically chemically RB cord-014597-66vd2mdu 2364 39 defined define VBN cord-014597-66vd2mdu 2364 40 production production NN cord-014597-66vd2mdu 2364 41 process process NN cord-014597-66vd2mdu 2364 42 for for IN cord-014597-66vd2mdu 2364 43 highly highly RB cord-014597-66vd2mdu 2364 44 attenuated attenuate VBN cord-014597-66vd2mdu 2364 45 poxviruses poxvirus NNS cord-014597-66vd2mdu 2365 1 A a DT cord-014597-66vd2mdu 2365 2 genotype genotype NN cord-014597-66vd2mdu 2365 3 of of IN cord-014597-66vd2mdu 2365 4 modified modify VBN cord-014597-66vd2mdu 2365 5 vaccinia vaccinia NN cord-014597-66vd2mdu 2365 6 Ankara Ankara NNP cord-014597-66vd2mdu 2365 7 ( ( -LRB- cord-014597-66vd2mdu 2365 8 MVA MVA NNP cord-014597-66vd2mdu 2365 9 ) ) -RRB- cord-014597-66vd2mdu 2365 10 that that WDT cord-014597-66vd2mdu 2365 11 facilitates facilitate VBZ cord-014597-66vd2mdu 2365 12 replication replication NN cord-014597-66vd2mdu 2365 13 in in IN cord-014597-66vd2mdu 2365 14 suspension suspension NN cord-014597-66vd2mdu 2365 15 cultures culture NNS cord-014597-66vd2mdu 2365 16 in in IN cord-014597-66vd2mdu 2365 17 chemically chemically RB cord-014597-66vd2mdu 2365 18 defined define VBN cord-014597-66vd2mdu 2365 19 medium medium NN cord-014597-66vd2mdu 2365 20 Easy easy JJ cord-014597-66vd2mdu 2365 21 and and CC cord-014597-66vd2mdu 2365 22 efficient efficient JJ cord-014597-66vd2mdu 2365 23 protocols protocol NNS cord-014597-66vd2mdu 2365 24 for for IN cord-014597-66vd2mdu 2365 25 working work VBG cord-014597-66vd2mdu 2365 26 with with IN cord-014597-66vd2mdu 2365 27 recombinant recombinant JJ cord-014597-66vd2mdu 2365 28 vaccinia vaccinia NN cord-014597-66vd2mdu 2365 29 virus virus NN cord-014597-66vd2mdu 2365 30 MVA MVA NNP cord-014597-66vd2mdu 2365 31 Large large JJ cord-014597-66vd2mdu 2365 32 - - HYPH cord-014597-66vd2mdu 2365 33 scale scale NN cord-014597-66vd2mdu 2365 34 transfection transfection NN cord-014597-66vd2mdu 2365 35 of of IN cord-014597-66vd2mdu 2365 36 mammalian mammalian JJ cord-014597-66vd2mdu 2365 37 cells cell NNS cord-014597-66vd2mdu 2365 38 for for IN cord-014597-66vd2mdu 2365 39 the the DT cord-014597-66vd2mdu 2365 40 fast fast JJ cord-014597-66vd2mdu 2365 41 production production NN cord-014597-66vd2mdu 2365 42 of of IN cord-014597-66vd2mdu 2365 43 recombinant recombinant JJ cord-014597-66vd2mdu 2365 44 protein protein NN cord-014597-66vd2mdu 2365 45 Recombinant recombinant JJ cord-014597-66vd2mdu 2365 46 protein protein NN cord-014597-66vd2mdu 2365 47 production production NN cord-014597-66vd2mdu 2365 48 by by IN cord-014597-66vd2mdu 2365 49 large large JJ cord-014597-66vd2mdu 2365 50 - - HYPH cord-014597-66vd2mdu 2365 51 scale scale NN cord-014597-66vd2mdu 2365 52 transient transient JJ cord-014597-66vd2mdu 2365 53 gene gene NN cord-014597-66vd2mdu 2365 54 expression expression NN cord-014597-66vd2mdu 2365 55 in in IN cord-014597-66vd2mdu 2365 56 mammalian mammalian JJ cord-014597-66vd2mdu 2365 57 cells cell NNS cord-014597-66vd2mdu 2365 58 : : : cord-014597-66vd2mdu 2365 59 state state NN cord-014597-66vd2mdu 2365 60 of of IN cord-014597-66vd2mdu 2365 61 the the DT cord-014597-66vd2mdu 2365 62 art art NN cord-014597-66vd2mdu 2365 63 and and CC cord-014597-66vd2mdu 2365 64 future future JJ cord-014597-66vd2mdu 2365 65 perspectives perspective NNS cord-014597-66vd2mdu 2365 66 High high JJ cord-014597-66vd2mdu 2365 67 density density NN cord-014597-66vd2mdu 2365 68 transfection transfection NN cord-014597-66vd2mdu 2365 69 with with IN cord-014597-66vd2mdu 2365 70 HEK HEK NNP cord-014597-66vd2mdu 2365 71 293 293 CD cord-014597-66vd2mdu 2365 72 cells cell NNS cord-014597-66vd2mdu 2365 73 allows allow VBZ cord-014597-66vd2mdu 2365 74 doubling double VBG cord-014597-66vd2mdu 2365 75 of of IN cord-014597-66vd2mdu 2365 76 transient transient JJ cord-014597-66vd2mdu 2365 77 titers titer NNS cord-014597-66vd2mdu 2365 78 and and CC cord-014597-66vd2mdu 2365 79 removes remove VBZ cord-014597-66vd2mdu 2365 80 need need NN cord-014597-66vd2mdu 2365 81 for for IN cord-014597-66vd2mdu 2365 82 a a DT cord-014597-66vd2mdu 2365 83 priori priori FW cord-014597-66vd2mdu 2365 84 DNA dna NN cord-014597-66vd2mdu 2365 85 complex complex JJ cord-014597-66vd2mdu 2365 86 formation formation NN cord-014597-66vd2mdu 2365 87 with with IN cord-014597-66vd2mdu 2365 88 PEI PEI NNP cord-014597-66vd2mdu 2365 89 Regulation Regulation NNP cord-014597-66vd2mdu 2365 90 of of IN cord-014597-66vd2mdu 2365 91 recombinant recombinant JJ cord-014597-66vd2mdu 2365 92 protein protein NN cord-014597-66vd2mdu 2365 93 expression expression NN cord-014597-66vd2mdu 2365 94 during during IN cord-014597-66vd2mdu 2365 95 CHOBRI CHOBRI NNP cord-014597-66vd2mdu 2365 96 / / SYM cord-014597-66vd2mdu 2365 97 rcTA rcTA NNP cord-014597-66vd2mdu 2365 98 pool pool NN cord-014597-66vd2mdu 2365 99 generation generation NN cord-014597-66vd2mdu 2365 100 increases increase VBZ cord-014597-66vd2mdu 2365 101 productivity productivity NN cord-014597-66vd2mdu 2365 102 and and CC cord-014597-66vd2mdu 2365 103 stability stability NN cord-014597-66vd2mdu 2365 104 QC QC NNP cord-014597-66vd2mdu 2365 105 , , , cord-014597-66vd2mdu 2365 106 Canada Canada NNP cord-014597-66vd2mdu 2365 107 ; ; : cord-014597-66vd2mdu 2365 108 2 2 CD cord-014597-66vd2mdu 2365 109 Department Department NNP cord-014597-66vd2mdu 2365 110 of of IN cord-014597-66vd2mdu 2365 111 microbiology microbiology NN cord-014597-66vd2mdu 2365 112 , , , cord-014597-66vd2mdu 2365 113 infectiology infectiology NN cord-014597-66vd2mdu 2365 114 and and CC cord-014597-66vd2mdu 2365 115 immunology immunology NN cord-014597-66vd2mdu 2366 1 The the DT cord-014597-66vd2mdu 2366 2 cumate cumate NN cord-014597-66vd2mdu 2366 3 gene gene NN cord-014597-66vd2mdu 2366 4 - - HYPH cord-014597-66vd2mdu 2366 5 switch switch NN cord-014597-66vd2mdu 2366 6 : : : cord-014597-66vd2mdu 2366 7 a a DT cord-014597-66vd2mdu 2366 8 system system NN cord-014597-66vd2mdu 2366 9 for for IN cord-014597-66vd2mdu 2366 10 regulated regulated JJ cord-014597-66vd2mdu 2366 11 expression expression NN cord-014597-66vd2mdu 2366 12 in in IN cord-014597-66vd2mdu 2366 13 mammalian mammalian JJ cord-014597-66vd2mdu 2366 14 cells cell NNS cord-014597-66vd2mdu 2366 15 Rapid rapid JJ cord-014597-66vd2mdu 2366 16 protein protein NN cord-014597-66vd2mdu 2366 17 production production NN cord-014597-66vd2mdu 2366 18 from from IN cord-014597-66vd2mdu 2366 19 stable stable JJ cord-014597-66vd2mdu 2366 20 CHO CHO NNP cord-014597-66vd2mdu 2366 21 cell cell NN cord-014597-66vd2mdu 2366 22 pools pool NNS cord-014597-66vd2mdu 2366 23 using use VBG cord-014597-66vd2mdu 2366 24 plasmid plasmid NN cord-014597-66vd2mdu 2366 25 vector vector NN cord-014597-66vd2mdu 2366 26 and and CC cord-014597-66vd2mdu 2366 27 the the DT cord-014597-66vd2mdu 2366 28 cumate cumate NNP cord-014597-66vd2mdu 2366 29 gene gene NN cord-014597-66vd2mdu 2366 30 - - HYPH cord-014597-66vd2mdu 2366 31 switch switch NN cord-014597-66vd2mdu 2366 32 Christoph Christoph NNP cord-014597-66vd2mdu 2366 33 Zehe Zehe NNP cord-014597-66vd2mdu 2366 34 Sartorius Sartorius NNP cord-014597-66vd2mdu 2366 35 Stedim Stedim NNP cord-014597-66vd2mdu 2366 36 Cellca Cellca NNP cord-014597-66vd2mdu 2366 37 GmbH GmbH NNP cord-014597-66vd2mdu 2366 38 , , , cord-014597-66vd2mdu 2366 39 88471 88471 CD cord-014597-66vd2mdu 2366 40 Laupheim Laupheim NNP cord-014597-66vd2mdu 2366 41 Animal Animal NNP cord-014597-66vd2mdu 2366 42 Cell Cell NNP cord-014597-66vd2mdu 2366 43 Technology Technology NNP cord-014597-66vd2mdu 2366 44 : : : cord-014597-66vd2mdu 2367 1 From from IN cord-014597-66vd2mdu 2367 2 Target Target NNP cord-014597-66vd2mdu 2367 3 to to IN cord-014597-66vd2mdu 2368 1 Market Market NNP cord-014597-66vd2mdu 2368 2 Recent recent JJ cord-014597-66vd2mdu 2368 3 advances advance NNS cord-014597-66vd2mdu 2368 4 in in IN cord-014597-66vd2mdu 2368 5 mammalian mammalian JJ cord-014597-66vd2mdu 2368 6 protein protein NN cord-014597-66vd2mdu 2368 7 production production NN cord-014597-66vd2mdu 2368 8 Molecular Molecular NNP cord-014597-66vd2mdu 2368 9 mechanisms mechanism NNS cord-014597-66vd2mdu 2368 10 of of IN cord-014597-66vd2mdu 2368 11 RNA RNA NNP cord-014597-66vd2mdu 2368 12 interference interference NN cord-014597-66vd2mdu 2368 13 . . . cord-014597-66vd2mdu 2369 1 Annual annual JJ cord-014597-66vd2mdu 2369 2 review review NN cord-014597-66vd2mdu 2369 3 of of IN cord-014597-66vd2mdu 2369 4 biophysics biophysics NNP cord-014597-66vd2mdu 2369 5 Ribosome Ribosome NNP cord-014597-66vd2mdu 2369 6 profiling profiling NN cord-014597-66vd2mdu 2369 7 - - HYPH cord-014597-66vd2mdu 2369 8 guided guide VBN cord-014597-66vd2mdu 2369 9 depletion depletion NN cord-014597-66vd2mdu 2369 10 of of IN cord-014597-66vd2mdu 2369 11 an an DT cord-014597-66vd2mdu 2369 12 mRNA mRNA NNP cord-014597-66vd2mdu 2369 13 increases increase VBZ cord-014597-66vd2mdu 2369 14 cell cell NN cord-014597-66vd2mdu 2369 15 growth growth NN cord-014597-66vd2mdu 2369 16 rate rate NN cord-014597-66vd2mdu 2369 17 and and CC cord-014597-66vd2mdu 2369 18 protein protein NN cord-014597-66vd2mdu 2369 19 secretion secretion NN cord-014597-66vd2mdu 2370 1 Ubiquitous Ubiquitous NNP cord-014597-66vd2mdu 2370 2 Chromatin Chromatin NNP cord-014597-66vd2mdu 2370 3 - - HYPH cord-014597-66vd2mdu 2370 4 opening open VBG cord-014597-66vd2mdu 2370 5 Elements element NNS cord-014597-66vd2mdu 2370 6 ( ( -LRB- cord-014597-66vd2mdu 2370 7 UCOEs ucoe NNS cord-014597-66vd2mdu 2370 8 ) ) -RRB- cord-014597-66vd2mdu 2370 9 : : : cord-014597-66vd2mdu 2371 1 Applications application NNS cord-014597-66vd2mdu 2371 2 in in IN cord-014597-66vd2mdu 2371 3 biomanufacturing biomanufacturing NN cord-014597-66vd2mdu 2371 4 and and CC cord-014597-66vd2mdu 2371 5 gene gene NN cord-014597-66vd2mdu 2371 6 therapy therapy NN cord-014597-66vd2mdu 2372 1 The the DT cord-014597-66vd2mdu 2372 2 art art NN cord-014597-66vd2mdu 2372 3 of of IN cord-014597-66vd2mdu 2372 4 CHO CHO NNP cord-014597-66vd2mdu 2372 5 cell cell NN cord-014597-66vd2mdu 2372 6 engineering engineering NN cord-014597-66vd2mdu 2372 7 : : : cord-014597-66vd2mdu 2373 1 A a DT cord-014597-66vd2mdu 2373 2 comprehensive comprehensive JJ cord-014597-66vd2mdu 2373 3 retrospect retrospect NN cord-014597-66vd2mdu 2373 4 and and CC cord-014597-66vd2mdu 2373 5 future future JJ cord-014597-66vd2mdu 2373 6 perspectives perspective NNS cord-014597-66vd2mdu 2374 1 A a DT cord-014597-66vd2mdu 2374 2 novel novel NN cord-014597-66vd2mdu 2374 3 Bxb1 Bxb1 NNP cord-014597-66vd2mdu 2374 4 integrase integrase NN cord-014597-66vd2mdu 2374 5 RMCE RMCE NNP cord-014597-66vd2mdu 2374 6 system system NN cord-014597-66vd2mdu 2374 7 for for IN cord-014597-66vd2mdu 2374 8 high high JJ cord-014597-66vd2mdu 2374 9 fidelity fidelity NN cord-014597-66vd2mdu 2374 10 site site NN cord-014597-66vd2mdu 2374 11 - - HYPH cord-014597-66vd2mdu 2374 12 specific specific JJ cord-014597-66vd2mdu 2374 13 integration integration NN cord-014597-66vd2mdu 2374 14 of of IN cord-014597-66vd2mdu 2374 15 mAb mab JJ cord-014597-66vd2mdu 2374 16 expression expression NN cord-014597-66vd2mdu 2374 17 cassette cassette NN cord-014597-66vd2mdu 2374 18 in in IN cord-014597-66vd2mdu 2374 19 CHO CHO NNP cord-014597-66vd2mdu 2374 20 Cells Cells NNP cord-014597-66vd2mdu 2374 21 High High NNP cord-014597-66vd2mdu 2374 22 - - HYPH cord-014597-66vd2mdu 2374 23 troughput troughput NN cord-014597-66vd2mdu 2374 24 Lipidomic Lipidomic NNP cord-014597-66vd2mdu 2374 25 and and CC cord-014597-66vd2mdu 2374 26 Transcriptomic Transcriptomic NNP cord-014597-66vd2mdu 2374 27 Analysis Analysis NNP cord-014597-66vd2mdu 2374 28 to to TO cord-014597-66vd2mdu 2374 29 Compare compare VB cord-014597-66vd2mdu 2375 1 SP2/0 SP2/0 NNP cord-014597-66vd2mdu 2375 2 , , , cord-014597-66vd2mdu 2375 3 CHO CHO NNP cord-014597-66vd2mdu 2375 4 , , , cord-014597-66vd2mdu 2375 5 and and CC cord-014597-66vd2mdu 2375 6 HEK-293 HEK-293 NNP cord-014597-66vd2mdu 2375 7 Mammalian Mammalian NNP cord-014597-66vd2mdu 2375 8 Cell Cell NNP cord-014597-66vd2mdu 2375 9 Lines Lines NNP cord-014597-66vd2mdu 2375 10 Single single JJ cord-014597-66vd2mdu 2375 11 cell cell NN cord-014597-66vd2mdu 2375 12 characterisation characterisation NN cord-014597-66vd2mdu 2375 13 of of IN cord-014597-66vd2mdu 2375 14 Chinese chinese JJ cord-014597-66vd2mdu 2375 15 hamster hamster NN cord-014597-66vd2mdu 2375 16 ovary ovary NN cord-014597-66vd2mdu 2375 17 ( ( -LRB- cord-014597-66vd2mdu 2375 18 CHO CHO NNP cord-014597-66vd2mdu 2375 19 ) ) -RRB- cord-014597-66vd2mdu 2375 20 cells cell NNS cord-014597-66vd2mdu 2375 21 Eva Eva NNP cord-014597-66vd2mdu 2375 22 Pekle Pekle NNP cord-014597-66vd2mdu 2375 23 1,2 1,2 CD cord-014597-66vd2mdu 2375 24 , , , cord-014597-66vd2mdu 2375 25 Guglielmo Guglielmo NNP cord-014597-66vd2mdu 2375 26 Rosignoli Rosignoli NNP cord-014597-66vd2mdu 2376 1 1 1 LS cord-014597-66vd2mdu 2376 2 Generation generation NN cord-014597-66vd2mdu 2376 3 of of IN cord-014597-66vd2mdu 2376 4 stable stable JJ cord-014597-66vd2mdu 2376 5 Chinese chinese JJ cord-014597-66vd2mdu 2376 6 hamster hamster NN cord-014597-66vd2mdu 2376 7 ovary ovary NN cord-014597-66vd2mdu 2376 8 pools pool NNS cord-014597-66vd2mdu 2376 9 yielding yield VBG cord-014597-66vd2mdu 2376 10 antibody antibody NN cord-014597-66vd2mdu 2376 11 titers titer NNS cord-014597-66vd2mdu 2376 12 of of IN cord-014597-66vd2mdu 2376 13 up up IN cord-014597-66vd2mdu 2376 14 to to TO cord-014597-66vd2mdu 2376 15 7.6 7.6 CD cord-014597-66vd2mdu 2376 16 g g NN cord-014597-66vd2mdu 2376 17 / / SYM cord-014597-66vd2mdu 2376 18 L l NN cord-014597-66vd2mdu 2376 19 using use VBG cord-014597-66vd2mdu 2376 20 the the DT cord-014597-66vd2mdu 2376 21 piggyBac piggybac JJ cord-014597-66vd2mdu 2376 22 transposon transposon NN cord-014597-66vd2mdu 2376 23 system system NN cord-014597-66vd2mdu 2376 24 Comparison Comparison NNP cord-014597-66vd2mdu 2376 25 of of IN cord-014597-66vd2mdu 2376 26 three three CD cord-014597-66vd2mdu 2376 27 transposons transposon NNS cord-014597-66vd2mdu 2376 28 for for IN cord-014597-66vd2mdu 2376 29 the the DT cord-014597-66vd2mdu 2376 30 generation generation NN cord-014597-66vd2mdu 2376 31 of of IN cord-014597-66vd2mdu 2376 32 highly highly RB cord-014597-66vd2mdu 2376 33 productive productive JJ cord-014597-66vd2mdu 2376 34 recombinant recombinant JJ cord-014597-66vd2mdu 2376 35 CHO CHO NNP cord-014597-66vd2mdu 2376 36 cell cell NN cord-014597-66vd2mdu 2376 37 pools pool NNS cord-014597-66vd2mdu 2376 38 and and CC cord-014597-66vd2mdu 2376 39 cell cell NN cord-014597-66vd2mdu 2376 40 lines line NNS cord-014597-66vd2mdu 2376 41 Effects effect NNS cord-014597-66vd2mdu 2376 42 of of IN cord-014597-66vd2mdu 2376 43 ammonia ammonia NN cord-014597-66vd2mdu 2376 44 and and CC cord-014597-66vd2mdu 2376 45 lactate lactate NN cord-014597-66vd2mdu 2376 46 on on IN cord-014597-66vd2mdu 2376 47 hybridoma hybridoma NN cord-014597-66vd2mdu 2376 48 growth growth NN cord-014597-66vd2mdu 2376 49 , , , cord-014597-66vd2mdu 2376 50 metabolism metabolism NN cord-014597-66vd2mdu 2376 51 , , , cord-014597-66vd2mdu 2376 52 and and CC cord-014597-66vd2mdu 2376 53 antibody antibody NN cord-014597-66vd2mdu 2376 54 production production NN cord-014597-66vd2mdu 2376 55 Lactate lactate NN cord-014597-66vd2mdu 2376 56 and and CC cord-014597-66vd2mdu 2376 57 glucose glucose NN cord-014597-66vd2mdu 2376 58 concomitant concomitant JJ cord-014597-66vd2mdu 2376 59 consumption consumption NN cord-014597-66vd2mdu 2376 60 as as IN cord-014597-66vd2mdu 2376 61 a a DT cord-014597-66vd2mdu 2376 62 self self NN cord-014597-66vd2mdu 2376 63 - - HYPH cord-014597-66vd2mdu 2376 64 regulated regulate VBN cord-014597-66vd2mdu 2376 65 pH pH NNP cord-014597-66vd2mdu 2376 66 detoxification detoxification NN cord-014597-66vd2mdu 2376 67 mechanism mechanism NN cord-014597-66vd2mdu 2376 68 in in IN cord-014597-66vd2mdu 2376 69 HEK293 HEK293 NNP cord-014597-66vd2mdu 2376 70 cell cell NN cord-014597-66vd2mdu 2376 71 cultures culture NNS cord-014597-66vd2mdu 2377 1 Flux flux NN cord-014597-66vd2mdu 2377 2 balance balance NN cord-014597-66vd2mdu 2377 3 analysis analysis NN cord-014597-66vd2mdu 2377 4 of of IN cord-014597-66vd2mdu 2377 5 CHO CHO NNP cord-014597-66vd2mdu 2377 6 cells cell NNS cord-014597-66vd2mdu 2377 7 before before RB cord-014597-66vd2mdu 2377 8 and and CC cord-014597-66vd2mdu 2377 9 after after IN cord-014597-66vd2mdu 2377 10 a a DT cord-014597-66vd2mdu 2377 11 metabolic metabolic JJ cord-014597-66vd2mdu 2377 12 switch switch NN cord-014597-66vd2mdu 2377 13 from from IN cord-014597-66vd2mdu 2377 14 lactate lactate NN cord-014597-66vd2mdu 2377 15 production production NN cord-014597-66vd2mdu 2377 16 to to IN cord-014597-66vd2mdu 2377 17 consumption consumption NN cord-014597-66vd2mdu 2377 18 Reducing reduce VBG cord-014597-66vd2mdu 2377 19 Recon Recon NNP cord-014597-66vd2mdu 2377 20 2 2 CD cord-014597-66vd2mdu 2377 21 for for IN cord-014597-66vd2mdu 2377 22 steady steady JJ cord-014597-66vd2mdu 2377 23 - - HYPH cord-014597-66vd2mdu 2377 24 state state NN cord-014597-66vd2mdu 2377 25 flux flux NN cord-014597-66vd2mdu 2377 26 analysis analysis NN cord-014597-66vd2mdu 2377 27 of of IN cord-014597-66vd2mdu 2377 28 HEK HEK NNP cord-014597-66vd2mdu 2377 29 cell cell NN cord-014597-66vd2mdu 2377 30 culture culture NN cord-014597-66vd2mdu 2378 1 Trastuzumab Trastuzumab NNP cord-014597-66vd2mdu 2378 2 -Mechanism -mechanism NN cord-014597-66vd2mdu 2378 3 of of IN cord-014597-66vd2mdu 2378 4 action action NN cord-014597-66vd2mdu 2378 5 and and CC cord-014597-66vd2mdu 2378 6 use use NN cord-014597-66vd2mdu 2378 7 in in IN cord-014597-66vd2mdu 2378 8 clinical clinical JJ cord-014597-66vd2mdu 2378 9 practice practice NN cord-014597-66vd2mdu 2378 10 HEK293 HEK293 NNP cord-014597-66vd2mdu 2378 11 cell cell NN cord-014597-66vd2mdu 2378 12 culture culture NN cord-014597-66vd2mdu 2378 13 media medium NNS cord-014597-66vd2mdu 2378 14 study study NN cord-014597-66vd2mdu 2378 15 towards towards IN cord-014597-66vd2mdu 2378 16 bioprocess bioprocess NN cord-014597-66vd2mdu 2378 17 optimization optimization NN cord-014597-66vd2mdu 2378 18 : : : cord-014597-66vd2mdu 2378 19 Animal animal NN cord-014597-66vd2mdu 2378 20 derived derive VBN cord-014597-66vd2mdu 2378 21 component component NN cord-014597-66vd2mdu 2378 22 free free JJ cord-014597-66vd2mdu 2378 23 and and CC cord-014597-66vd2mdu 2378 24 animal animal NN cord-014597-66vd2mdu 2378 25 derived derive VBN cord-014597-66vd2mdu 2378 26 component component NN cord-014597-66vd2mdu 2378 27 containing contain VBG cord-014597-66vd2mdu 2378 28 platforms platform NNS cord-014597-66vd2mdu 2378 29 Enhancing enhance VBG cord-014597-66vd2mdu 2378 30 heterologous heterologous JJ cord-014597-66vd2mdu 2378 31 protein protein NN cord-014597-66vd2mdu 2378 32 expression expression NN cord-014597-66vd2mdu 2378 33 and and CC cord-014597-66vd2mdu 2378 34 secretion secretion NN cord-014597-66vd2mdu 2378 35 in in IN cord-014597-66vd2mdu 2378 36 HEK293 HEK293 NNP cord-014597-66vd2mdu 2378 37 cells cell NNS cord-014597-66vd2mdu 2378 38 by by IN cord-014597-66vd2mdu 2378 39 means mean NNS cord-014597-66vd2mdu 2378 40 of of IN cord-014597-66vd2mdu 2378 41 combination combination NN cord-014597-66vd2mdu 2378 42 of of IN cord-014597-66vd2mdu 2378 43 CMV CMV NNP cord-014597-66vd2mdu 2378 44 promoter promoter NN cord-014597-66vd2mdu 2378 45 and and CC cord-014597-66vd2mdu 2378 46 IFNα2 ifnα2 JJ cord-014597-66vd2mdu 2378 47 signal signal NN cord-014597-66vd2mdu 2378 48 peptide peptide NN cord-014597-66vd2mdu 2378 49 Production Production NNP cord-014597-66vd2mdu 2378 50 of of IN cord-014597-66vd2mdu 2378 51 lentiviral lentiviral JJ cord-014597-66vd2mdu 2378 52 vectors vector NNS cord-014597-66vd2mdu 2379 1 References reference NNS cord-014597-66vd2mdu 2379 2 1 1 CD cord-014597-66vd2mdu 2379 3 . . . cord-014597-66vd2mdu 2380 1 Wurm Wurm NNP cord-014597-66vd2mdu 2380 2 F F NNP cord-014597-66vd2mdu 2380 3 M M NNP cord-014597-66vd2mdu 2380 4 : : : cord-014597-66vd2mdu 2380 5 Production production NN cord-014597-66vd2mdu 2380 6 of of IN cord-014597-66vd2mdu 2380 7 recombinant recombinant JJ cord-014597-66vd2mdu 2380 8 protein protein NN cord-014597-66vd2mdu 2380 9 therapeutics therapeutic NNS cord-014597-66vd2mdu 2380 10 in in IN cord-014597-66vd2mdu 2380 11 cultivated cultivate VBN cord-014597-66vd2mdu 2380 12 mamammalian mamammalian NN cord-014597-66vd2mdu 2380 13 cells cell NNS cord-014597-66vd2mdu 2380 14 Initial initial JJ cord-014597-66vd2mdu 2380 15 identification identification NN cord-014597-66vd2mdu 2380 16 of of IN cord-014597-66vd2mdu 2380 17 low low JJ cord-014597-66vd2mdu 2380 18 temperature temperature NN cord-014597-66vd2mdu 2380 19 and and CC cord-014597-66vd2mdu 2380 20 culture culture NN cord-014597-66vd2mdu 2380 21 stage stage NN cord-014597-66vd2mdu 2380 22 induction induction NN cord-014597-66vd2mdu 2380 23 of of IN cord-014597-66vd2mdu 2380 24 miRNA miRNA NNP cord-014597-66vd2mdu 2380 25 expression expression NN cord-014597-66vd2mdu 2380 26 in in IN cord-014597-66vd2mdu 2380 27 suspension suspension NN cord-014597-66vd2mdu 2380 28 CHO CHO NNP cord-014597-66vd2mdu 2380 29 - - HYPH cord-014597-66vd2mdu 2380 30 K1 K1 NNP cord-014597-66vd2mdu 2380 31 cells cell NNS cord-014597-66vd2mdu 2380 32 Small small JJ cord-014597-66vd2mdu 2380 33 indels indel NNS cord-014597-66vd2mdu 2380 34 induced induce VBN cord-014597-66vd2mdu 2380 35 by by IN cord-014597-66vd2mdu 2380 36 CRISPR CRISPR NNP cord-014597-66vd2mdu 2380 37 / / SYM cord-014597-66vd2mdu 2380 38 Cas9 Cas9 NNP cord-014597-66vd2mdu 2380 39 in in IN cord-014597-66vd2mdu 2380 40 the the DT cord-014597-66vd2mdu 2380 41 5 5 CD cord-014597-66vd2mdu 2380 42 ' ' '' cord-014597-66vd2mdu 2380 43 region region NN cord-014597-66vd2mdu 2380 44 of of IN cord-014597-66vd2mdu 2380 45 microRNA microRNA NNP cord-014597-66vd2mdu 2380 46 lead lead NN cord-014597-66vd2mdu 2380 47 to to IN cord-014597-66vd2mdu 2380 48 its -PRON- PRP$ cord-014597-66vd2mdu 2380 49 depletion depletion NN cord-014597-66vd2mdu 2380 50 and and CC cord-014597-66vd2mdu 2380 51 Drosha Drosha NNP cord-014597-66vd2mdu 2380 52 processing processing NN cord-014597-66vd2mdu 2380 53 retardance retardance NN cord-014597-66vd2mdu 2380 54 Production production NN cord-014597-66vd2mdu 2380 55 of of IN cord-014597-66vd2mdu 2380 56 recombinant recombinant JJ cord-014597-66vd2mdu 2380 57 protein protein NN cord-014597-66vd2mdu 2380 58 therapeutics therapeutic NNS cord-014597-66vd2mdu 2380 59 in in IN cord-014597-66vd2mdu 2380 60 cultivated cultivate VBN cord-014597-66vd2mdu 2380 61 mammalian mammalian JJ cord-014597-66vd2mdu 2380 62 cells cell NNS cord-014597-66vd2mdu 2380 63 Improved improve VBN cord-014597-66vd2mdu 2380 64 antibody antibody NN cord-014597-66vd2mdu 2380 65 production production NN cord-014597-66vd2mdu 2380 66 in in IN cord-014597-66vd2mdu 2380 67 Chinese chinese JJ cord-014597-66vd2mdu 2380 68 hamster hamster NN cord-014597-66vd2mdu 2380 69 ovary ovary NN cord-014597-66vd2mdu 2380 70 cells cell NNS cord-014597-66vd2mdu 2380 71 by by IN cord-014597-66vd2mdu 2380 72 ATF4 ATF4 NNP cord-014597-66vd2mdu 2380 73 overexpression overexpression NN cord-014597-66vd2mdu 2381 1 The the DT cord-014597-66vd2mdu 2381 2 vesicle vesicle NN cord-014597-66vd2mdu 2381 3 - - HYPH cord-014597-66vd2mdu 2381 4 trafficking traffic VBG cord-014597-66vd2mdu 2381 5 protein protein NN cord-014597-66vd2mdu 2381 6 munc18b munc18b NNP cord-014597-66vd2mdu 2381 7 increases increase VBZ cord-014597-66vd2mdu 2381 8 the the DT cord-014597-66vd2mdu 2381 9 secretory secretory JJ cord-014597-66vd2mdu 2381 10 capacity capacity NN cord-014597-66vd2mdu 2381 11 of of IN cord-014597-66vd2mdu 2381 12 mammalian mammalian JJ cord-014597-66vd2mdu 2381 13 cells cell NNS cord-014597-66vd2mdu 2381 14 Rapid rapid JJ cord-014597-66vd2mdu 2381 15 evaluation evaluation NN cord-014597-66vd2mdu 2381 16 of of IN cord-014597-66vd2mdu 2381 17 N n CD cord-014597-66vd2mdu 2381 18 - - HYPH cord-014597-66vd2mdu 2381 19 glycosylation glycosylation NN cord-014597-66vd2mdu 2381 20 status status NN cord-014597-66vd2mdu 2381 21 of of IN cord-014597-66vd2mdu 2381 22 antibodies antibody NNS cord-014597-66vd2mdu 2381 23 with with IN cord-014597-66vd2mdu 2381 24 chemiluminescent chemiluminescent NN cord-014597-66vd2mdu 2381 25 lectin lectin NN cord-014597-66vd2mdu 2381 26 - - HYPH cord-014597-66vd2mdu 2381 27 binding bind VBG cord-014597-66vd2mdu 2381 28 assay assay NN cord-014597-66vd2mdu 2382 1 Intracellular Intracellular NNP cord-014597-66vd2mdu 2382 2 secretion secretion NN cord-014597-66vd2mdu 2382 3 pathway pathway NN cord-014597-66vd2mdu 2382 4 analysis analysis NN cord-014597-66vd2mdu 2382 5 for for IN cord-014597-66vd2mdu 2382 6 constructing construct VBG cord-014597-66vd2mdu 2382 7 highly highly RB cord-014597-66vd2mdu 2382 8 producible producible JJ cord-014597-66vd2mdu 2382 9 engineered engineer VBN cord-014597-66vd2mdu 2382 10 CHO CHO NNP cord-014597-66vd2mdu 2382 11 cells cell NNS cord-014597-66vd2mdu 2382 12 . . . cord-014597-66vd2mdu 2383 1 16th 16th NNP cord-014597-66vd2mdu 2383 2 annual annual NNP cord-014597-66vd2mdu 2383 3 peptalk peptalk NNP cord-014597-66vd2mdu 2383 4 Intracellular Intracellular NNP cord-014597-66vd2mdu 2383 5 secretion secretion NN cord-014597-66vd2mdu 2383 6 analysis analysis NN cord-014597-66vd2mdu 2383 7 of of IN cord-014597-66vd2mdu 2383 8 therapeutic therapeutic JJ cord-014597-66vd2mdu 2383 9 antibodies antibody NNS cord-014597-66vd2mdu 2383 10 in in IN cord-014597-66vd2mdu 2383 11 engineered engineer VBN cord-014597-66vd2mdu 2383 12 high high RB cord-014597-66vd2mdu 2383 13 - - HYPH cord-014597-66vd2mdu 2383 14 producible producible JJ cord-014597-66vd2mdu 2383 15 CHO CHO NNP cord-014597-66vd2mdu 2383 16 cells cell NNS cord-014597-66vd2mdu 2383 17 Analysis Analysis NNP cord-014597-66vd2mdu 2383 18 of of IN cord-014597-66vd2mdu 2383 19 intracellular intracellular JJ cord-014597-66vd2mdu 2383 20 recombinant recombinant JJ cord-014597-66vd2mdu 2383 21 IgG igg NN cord-014597-66vd2mdu 2383 22 secretion secretion NN cord-014597-66vd2mdu 2383 23 in in IN cord-014597-66vd2mdu 2383 24 engineered engineer VBN cord-014597-66vd2mdu 2383 25 CHO CHO NNP cord-014597-66vd2mdu 2383 26 cells cell NNS cord-014597-66vd2mdu 2383 27 . . . cord-014597-66vd2mdu 2384 1 The the DT cord-014597-66vd2mdu 2384 2 29th 29th JJ cord-014597-66vd2mdu 2384 3 annual annual JJ cord-014597-66vd2mdu 2384 4 and and CC cord-014597-66vd2mdu 2384 5 international international JJ cord-014597-66vd2mdu 2384 6 meeting meeting NN cord-014597-66vd2mdu 2384 7 of of IN cord-014597-66vd2mdu 2384 8 the the DT cord-014597-66vd2mdu 2384 9 Japanese Japanese NNP cord-014597-66vd2mdu 2384 10 Association Association NNP cord-014597-66vd2mdu 2384 11 for for IN cord-014597-66vd2mdu 2384 12 animal animal NN cord-014597-66vd2mdu 2384 13 cell cell NN cord-014597-66vd2mdu 2384 14 technology technology NN cord-014597-66vd2mdu 2384 15 Humanization Humanization NNP cord-014597-66vd2mdu 2384 16 strategies strategy NNS cord-014597-66vd2mdu 2384 17 for for IN cord-014597-66vd2mdu 2384 18 an an DT cord-014597-66vd2mdu 2384 19 anti anti JJ cord-014597-66vd2mdu 2384 20 - - JJ cord-014597-66vd2mdu 2384 21 idiotypic idiotypic JJ cord-014597-66vd2mdu 2384 22 antibody antibody NN cord-014597-66vd2mdu 2384 23 mimicking mimic VBG cord-014597-66vd2mdu 2384 24 HIV HIV NNP cord-014597-66vd2mdu 2384 25 - - HYPH cord-014597-66vd2mdu 2384 26 I I NNP cord-014597-66vd2mdu 2384 27 gp41 gp41 NNP cord-014597-66vd2mdu 2384 28 Antibody Antibody NNP cord-014597-66vd2mdu 2384 29 humanization humanization NN cord-014597-66vd2mdu 2384 30 by by IN cord-014597-66vd2mdu 2384 31 molecular molecular JJ cord-014597-66vd2mdu 2384 32 dynamics dynamic NNS cord-014597-66vd2mdu 2384 33 simulations simulation NNS cord-014597-66vd2mdu 2384 34 - - HYPH cord-014597-66vd2mdu 2384 35 in in IN cord-014597-66vd2mdu 2384 36 - - HYPH cord-014597-66vd2mdu 2384 37 silico silico NN cord-014597-66vd2mdu 2384 38 guided guide VBN cord-014597-66vd2mdu 2384 39 selection selection NN cord-014597-66vd2mdu 2384 40 of of IN cord-014597-66vd2mdu 2384 41 critical critical JJ cord-014597-66vd2mdu 2384 42 backmutations backmutation NNS cord-014597-66vd2mdu 2384 43 MaxQuant MaxQuant NNP cord-014597-66vd2mdu 2384 44 enables enable VBZ cord-014597-66vd2mdu 2384 45 high high JJ cord-014597-66vd2mdu 2384 46 peptide peptide NN cord-014597-66vd2mdu 2384 47 identification identification NN cord-014597-66vd2mdu 2384 48 rates rate NNS cord-014597-66vd2mdu 2384 49 , , , cord-014597-66vd2mdu 2384 50 individualized individualized JJ cord-014597-66vd2mdu 2384 51 p.p.b.-range p.p.b.-range IN cord-014597-66vd2mdu 2384 52 mass mass NN cord-014597-66vd2mdu 2384 53 accuracies accuracy NNS cord-014597-66vd2mdu 2384 54 and and CC cord-014597-66vd2mdu 2384 55 proteome proteome NN cord-014597-66vd2mdu 2384 56 - - HYPH cord-014597-66vd2mdu 2384 57 wide wide JJ cord-014597-66vd2mdu 2384 58 protein protein NN cord-014597-66vd2mdu 2384 59 quantification quantification NN cord-014597-66vd2mdu 2385 1 The the DT cord-014597-66vd2mdu 2385 2 Perseus Perseus NNP cord-014597-66vd2mdu 2385 3 computational computational JJ cord-014597-66vd2mdu 2385 4 platform platform NN cord-014597-66vd2mdu 2385 5 for for IN cord-014597-66vd2mdu 2385 6 comprehensive comprehensive JJ cord-014597-66vd2mdu 2385 7 analysis analysis NN cord-014597-66vd2mdu 2385 8 of of IN cord-014597-66vd2mdu 2386 1 ( ( -LRB- cord-014597-66vd2mdu 2386 2 prote)omics prote)omics NNP cord-014597-66vd2mdu 2386 3 data datum NNS cord-014597-66vd2mdu 2386 4 Hoffrogge hoffrogge NN cord-014597-66vd2mdu 2386 5 : : : cord-014597-66vd2mdu 2386 6 Label label NN cord-014597-66vd2mdu 2386 7 - - HYPH cord-014597-66vd2mdu 2386 8 free free JJ cord-014597-66vd2mdu 2386 9 protein protein NN cord-014597-66vd2mdu 2386 10 quantification quantification NN cord-014597-66vd2mdu 2386 11 of of IN cord-014597-66vd2mdu 2386 12 sodium sodium NN cord-014597-66vd2mdu 2386 13 butyrate butyrate NN cord-014597-66vd2mdu 2386 14 treated treat VBD cord-014597-66vd2mdu 2386 15 CHO CHO NNP cord-014597-66vd2mdu 2386 16 cells cell NNS cord-014597-66vd2mdu 2386 17 by by IN cord-014597-66vd2mdu 2386 18 ESI ESI NNP cord-014597-66vd2mdu 2386 19 - - HYPH cord-014597-66vd2mdu 2386 20 UHR UHR NNP cord-014597-66vd2mdu 2386 21 - - HYPH cord-014597-66vd2mdu 2386 22 TOF TOF NNP cord-014597-66vd2mdu 2386 23 - - HYPH cord-014597-66vd2mdu 2386 24 MS MS NNP cord-014597-66vd2mdu 2387 1 The the DT cord-014597-66vd2mdu 2387 2 art art NN cord-014597-66vd2mdu 2387 3 of of IN cord-014597-66vd2mdu 2387 4 CHO CHO NNP cord-014597-66vd2mdu 2387 5 cell cell NN cord-014597-66vd2mdu 2387 6 engineering engineering NN cord-014597-66vd2mdu 2387 7 : : : cord-014597-66vd2mdu 2387 8 a a DT cord-014597-66vd2mdu 2387 9 comprehensive comprehensive JJ cord-014597-66vd2mdu 2387 10 retrospect retrospect NN cord-014597-66vd2mdu 2387 11 and and CC cord-014597-66vd2mdu 2387 12 future future JJ cord-014597-66vd2mdu 2387 13 perspectives perspective NNS cord-014597-66vd2mdu 2387 14 GS GS NNP cord-014597-66vd2mdu 2387 15 system system NN cord-014597-66vd2mdu 2387 16 for for IN cord-014597-66vd2mdu 2387 17 increased increased JJ cord-014597-66vd2mdu 2387 18 expression expression NN cord-014597-66vd2mdu 2387 19 of of IN cord-014597-66vd2mdu 2387 20 difficult difficult JJ cord-014597-66vd2mdu 2387 21 - - HYPH cord-014597-66vd2mdu 2387 22 to to TO cord-014597-66vd2mdu 2387 23 - - HYPH cord-014597-66vd2mdu 2387 24 express express NN cord-014597-66vd2mdu 2387 25 proteins protein NNS cord-014597-66vd2mdu 2388 1 The the DT cord-014597-66vd2mdu 2388 2 Netherlands Netherlands NNP cord-014597-66vd2mdu 2388 3 Correspondence Correspondence NNP cord-014597-66vd2mdu 2388 4 : : : cord-014597-66vd2mdu 2388 5 Maurice Maurice NNP cord-014597-66vd2mdu 2388 6 van van NNP cord-014597-66vd2mdu 2388 7 der der NNP cord-014597-66vd2mdu 2388 8 Heijden Heijden NNP cord-014597-66vd2mdu 2388 9 ( ( -LRB- cord-014597-66vd2mdu 2388 10 heijden@proteonic.nl heijden@proteonic.nl '' cord-014597-66vd2mdu 2388 11 ) ) -RRB- cord-014597-66vd2mdu 2389 1 BMC BMC NNP cord-014597-66vd2mdu 2389 2 Proceedings Proceedings NNP cord-014597-66vd2mdu 2389 3 Increased increase VBD cord-014597-66vd2mdu 2389 4 recombinant recombinant JJ cord-014597-66vd2mdu 2389 5 protein protein NN cord-014597-66vd2mdu 2389 6 production production NN cord-014597-66vd2mdu 2389 7 owing owe VBG cord-014597-66vd2mdu 2389 8 to to IN cord-014597-66vd2mdu 2389 9 expanded expand VBN cord-014597-66vd2mdu 2389 10 opportunities opportunity NNS cord-014597-66vd2mdu 2389 11 for for IN cord-014597-66vd2mdu 2389 12 vector vector NN cord-014597-66vd2mdu 2389 13 integration integration NN cord-014597-66vd2mdu 2389 14 in in IN cord-014597-66vd2mdu 2389 15 high high JJ cord-014597-66vd2mdu 2389 16 chromosome chromosome NN cord-014597-66vd2mdu 2389 17 number number NN cord-014597-66vd2mdu 2389 18 Chinese chinese JJ cord-014597-66vd2mdu 2389 19 hamster hamster NN cord-014597-66vd2mdu 2389 20 ovary ovary NN cord-014597-66vd2mdu 2389 21 cells cell NNS cord-014597-66vd2mdu 2389 22 IRES IRES NNP cord-014597-66vd2mdu 2389 23 - - HYPH cord-014597-66vd2mdu 2389 24 mediated mediate VBN cord-014597-66vd2mdu 2389 25 translation translation NN cord-014597-66vd2mdu 2389 26 of of IN cord-014597-66vd2mdu 2389 27 membrane membrane NN cord-014597-66vd2mdu 2389 28 proteins protein NNS cord-014597-66vd2mdu 2389 29 and and CC cord-014597-66vd2mdu 2389 30 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 2389 31 in in IN cord-014597-66vd2mdu 2389 32 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 2389 33 cell cell NN cord-014597-66vd2mdu 2389 34 - - HYPH cord-014597-66vd2mdu 2389 35 free free JJ cord-014597-66vd2mdu 2389 36 systems system NNS cord-014597-66vd2mdu 2389 37 Cell cell NN cord-014597-66vd2mdu 2389 38 - - HYPH cord-014597-66vd2mdu 2389 39 free free JJ cord-014597-66vd2mdu 2389 40 protein protein NN cord-014597-66vd2mdu 2389 41 expression expression NN cord-014597-66vd2mdu 2389 42 based base VBN cord-014597-66vd2mdu 2389 43 on on IN cord-014597-66vd2mdu 2389 44 extracts extract NNS cord-014597-66vd2mdu 2389 45 from from IN cord-014597-66vd2mdu 2389 46 CHO CHO NNP cord-014597-66vd2mdu 2389 47 cells cell NNS cord-014597-66vd2mdu 2389 48 Comparison comparison NN cord-014597-66vd2mdu 2389 49 of of IN cord-014597-66vd2mdu 2389 50 cell cell NN cord-014597-66vd2mdu 2389 51 - - HYPH cord-014597-66vd2mdu 2389 52 based base VBN cord-014597-66vd2mdu 2389 53 vs. vs. IN cord-014597-66vd2mdu 2389 54 cell cell NN cord-014597-66vd2mdu 2389 55 - - HYPH cord-014597-66vd2mdu 2389 56 free free JJ cord-014597-66vd2mdu 2389 57 mammalian mammalian JJ cord-014597-66vd2mdu 2389 58 systems system NNS cord-014597-66vd2mdu 2389 59 for for IN cord-014597-66vd2mdu 2389 60 the the DT cord-014597-66vd2mdu 2389 61 production production NN cord-014597-66vd2mdu 2389 62 of of IN cord-014597-66vd2mdu 2389 63 a a DT cord-014597-66vd2mdu 2389 64 recombinant recombinant JJ cord-014597-66vd2mdu 2389 65 human human JJ cord-014597-66vd2mdu 2389 66 bone bone NN cord-014597-66vd2mdu 2389 67 morphogenic morphogenic JJ cord-014597-66vd2mdu 2389 68 growth growth NN cord-014597-66vd2mdu 2389 69 factor factor NN cord-014597-66vd2mdu 2389 70 . . . cord-014597-66vd2mdu 2390 1 Eng Eng NNP cord-014597-66vd2mdu 2390 2 Dual dual JJ cord-014597-66vd2mdu 2390 3 - - HYPH cord-014597-66vd2mdu 2390 4 responsive responsive JJ cord-014597-66vd2mdu 2390 5 magnetic magnetic JJ cord-014597-66vd2mdu 2390 6 core core NN cord-014597-66vd2mdu 2390 7 - - HYPH cord-014597-66vd2mdu 2390 8 shell shell NN cord-014597-66vd2mdu 2390 9 nanoparticles nanoparticle NNS cord-014597-66vd2mdu 2390 10 for for IN cord-014597-66vd2mdu 2390 11 nonviral nonviral JJ cord-014597-66vd2mdu 2390 12 gene gene NN cord-014597-66vd2mdu 2390 13 delivery delivery NN cord-014597-66vd2mdu 2390 14 and and CC cord-014597-66vd2mdu 2390 15 cell cell NN cord-014597-66vd2mdu 2390 16 separation separation NN cord-014597-66vd2mdu 2390 17 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 2390 18 - - HYPH cord-014597-66vd2mdu 2390 19 grafted graft VBN cord-014597-66vd2mdu 2390 20 core core NN cord-014597-66vd2mdu 2390 21 - - HYPH cord-014597-66vd2mdu 2390 22 shell shell NN cord-014597-66vd2mdu 2390 23 - - HYPH cord-014597-66vd2mdu 2390 24 corona corona NN cord-014597-66vd2mdu 2390 25 particles particle NNS cord-014597-66vd2mdu 2390 26 for for IN cord-014597-66vd2mdu 2390 27 nonviral nonviral JJ cord-014597-66vd2mdu 2390 28 gene gene NN cord-014597-66vd2mdu 2390 29 delivery delivery NN cord-014597-66vd2mdu 2390 30 and and CC cord-014597-66vd2mdu 2390 31 magnetic magnetic JJ cord-014597-66vd2mdu 2390 32 cell cell NN cord-014597-66vd2mdu 2390 33 separation separation NN cord-014597-66vd2mdu 2390 34 Influence influence NN cord-014597-66vd2mdu 2390 35 of of IN cord-014597-66vd2mdu 2390 36 polyplex polyplex NNP cord-014597-66vd2mdu 2390 37 formation formation NN cord-014597-66vd2mdu 2390 38 on on IN cord-014597-66vd2mdu 2390 39 the the DT cord-014597-66vd2mdu 2390 40 performance performance NN cord-014597-66vd2mdu 2390 41 of of IN cord-014597-66vd2mdu 2390 42 starshaped starshaped NNP cord-014597-66vd2mdu 2390 43 polycationic polycationic NNP cord-014597-66vd2mdu 2390 44 transfection transfection NN cord-014597-66vd2mdu 2390 45 agents agent NNS cord-014597-66vd2mdu 2390 46 for for IN cord-014597-66vd2mdu 2390 47 mammalian mammalian JJ cord-014597-66vd2mdu 2390 48 cells cell NNS cord-014597-66vd2mdu 2390 49 Systematic systematic JJ cord-014597-66vd2mdu 2390 50 Study Study NNP cord-014597-66vd2mdu 2390 51 of of IN cord-014597-66vd2mdu 2390 52 a a DT cord-014597-66vd2mdu 2390 53 Library Library NNP cord-014597-66vd2mdu 2390 54 of of IN cord-014597-66vd2mdu 2390 55 PDMAEMA PDMAEMA NNP cord-014597-66vd2mdu 2390 56 - - HYPH cord-014597-66vd2mdu 2390 57 Based Based NNP cord-014597-66vd2mdu 2390 58 , , , cord-014597-66vd2mdu 2390 59 Superparamagnetic Superparamagnetic NNP cord-014597-66vd2mdu 2390 60 Nano Nano NNP cord-014597-66vd2mdu 2390 61 - - HYPH cord-014597-66vd2mdu 2390 62 Stars Stars NNP cord-014597-66vd2mdu 2390 63 for for IN cord-014597-66vd2mdu 2390 64 the the DT cord-014597-66vd2mdu 2390 65 Transfection Transfection NNP cord-014597-66vd2mdu 2390 66 of of IN cord-014597-66vd2mdu 2390 67 CHO CHO NNP cord-014597-66vd2mdu 2390 68 - - HYPH cord-014597-66vd2mdu 2390 69 K1 K1 NNP cord-014597-66vd2mdu 2390 70 Cells Cells NNPS cord-014597-66vd2mdu 2390 71 Systems Systems NNPS cord-014597-66vd2mdu 2390 72 biology biology NN cord-014597-66vd2mdu 2390 73 of of IN cord-014597-66vd2mdu 2390 74 unfolded unfold VBN cord-014597-66vd2mdu 2390 75 protein protein NN cord-014597-66vd2mdu 2390 76 response response NN cord-014597-66vd2mdu 2390 77 in in IN cord-014597-66vd2mdu 2390 78 recombinant recombinant JJ cord-014597-66vd2mdu 2390 79 CHO CHO NNP cord-014597-66vd2mdu 2390 80 cells cell NNS cord-014597-66vd2mdu 2390 81 Dynamics dynamic NNS cord-014597-66vd2mdu 2390 82 of of IN cord-014597-66vd2mdu 2390 83 unfolded unfold VBN cord-014597-66vd2mdu 2390 84 protein protein NN cord-014597-66vd2mdu 2390 85 response response NN cord-014597-66vd2mdu 2390 86 in in IN cord-014597-66vd2mdu 2390 87 recombinant recombinant JJ cord-014597-66vd2mdu 2390 88 CHO CHO NNP cord-014597-66vd2mdu 2390 89 cells cell NNS cord-014597-66vd2mdu 2390 90 Cells cell NNS cord-014597-66vd2mdu 2390 91 were be VBD cord-014597-66vd2mdu 2390 92 transfected transfecte VBN cord-014597-66vd2mdu 2390 93 with with IN cord-014597-66vd2mdu 2390 94 NP@(PDMAEMA NP@(PDMAEMA NNP cord-014597-66vd2mdu 2390 95 1037 1037 CD cord-014597-66vd2mdu 2390 96 ) ) -RRB- cord-014597-66vd2mdu 2391 1 46 46 CD cord-014597-66vd2mdu 2392 1 ( ( -LRB- cord-014597-66vd2mdu 2392 2 N N NNP cord-014597-66vd2mdu 2392 3 / / SYM cord-014597-66vd2mdu 2392 4 P P NNP cord-014597-66vd2mdu 2392 5 15 15 CD cord-014597-66vd2mdu 2392 6 ) ) -RRB- cord-014597-66vd2mdu 2392 7 , , , cord-014597-66vd2mdu 2392 8 separated separate VBD cord-014597-66vd2mdu 2392 9 24 24 CD cord-014597-66vd2mdu 2392 10 h h NN cord-014597-66vd2mdu 2392 11 post post NN cord-014597-66vd2mdu 2392 12 transfection transfection NN cord-014597-66vd2mdu 2392 13 ( ( -LRB- cord-014597-66vd2mdu 2392 14 t t NN cord-014597-66vd2mdu 2392 15 = = SYM cord-014597-66vd2mdu 2392 16 0 0 NFP cord-014597-66vd2mdu 2392 17 ) ) -RRB- cord-014597-66vd2mdu 2392 18 by by IN cord-014597-66vd2mdu 2392 19 magnetically magnetically RB cord-014597-66vd2mdu 2392 20 - - HYPH cord-014597-66vd2mdu 2392 21 assisted assist VBN cord-014597-66vd2mdu 2392 22 cell cell NN cord-014597-66vd2mdu 2392 23 sorting sorting NN cord-014597-66vd2mdu 2392 24 and and CC cord-014597-66vd2mdu 2392 25 placed place VBN cord-014597-66vd2mdu 2392 26 into into IN cord-014597-66vd2mdu 2392 27 separated separated JJ cord-014597-66vd2mdu 2392 28 cultures culture NNS cord-014597-66vd2mdu 2392 29 . . . cord-014597-66vd2mdu 2393 1 The the DT cord-014597-66vd2mdu 2393 2 bars bar NNS cord-014597-66vd2mdu 2393 3 represent represent VBP cord-014597-66vd2mdu 2393 4 the the DT cord-014597-66vd2mdu 2393 5 overall overall JJ cord-014597-66vd2mdu 2393 6 transfection transfection NN cord-014597-66vd2mdu 2393 7 efficiency efficiency NN cord-014597-66vd2mdu 2393 8 . . . cord-014597-66vd2mdu 2394 1 Distribution distribution NN cord-014597-66vd2mdu 2394 2 of of IN cord-014597-66vd2mdu 2394 3 low low JJ cord-014597-66vd2mdu 2394 4 ( ( -LRB- cord-014597-66vd2mdu 2394 5 light light JJ cord-014597-66vd2mdu 2394 6 green green JJ cord-014597-66vd2mdu 2394 7 ) ) -RRB- cord-014597-66vd2mdu 2394 8 , , , cord-014597-66vd2mdu 2394 9 middle middle JJ cord-014597-66vd2mdu 2394 10 ( ( -LRB- cord-014597-66vd2mdu 2394 11 green green JJ cord-014597-66vd2mdu 2394 12 ) ) -RRB- cord-014597-66vd2mdu 2394 13 , , , cord-014597-66vd2mdu 2394 14 and and CC cord-014597-66vd2mdu 2394 15 high high JJ cord-014597-66vd2mdu 2394 16 ( ( -LRB- cord-014597-66vd2mdu 2394 17 dark dark JJ cord-014597-66vd2mdu 2394 18 green green JJ cord-014597-66vd2mdu 2394 19 ) ) -RRB- cord-014597-66vd2mdu 2394 20 producers producer NNS cord-014597-66vd2mdu 2394 21 within within IN cord-014597-66vd2mdu 2394 22 the the DT cord-014597-66vd2mdu 2394 23 EGFP EGFP NNP cord-014597-66vd2mdu 2394 24 - - HYPH cord-014597-66vd2mdu 2394 25 expressing express VBG cord-014597-66vd2mdu 2394 26 cell cell NN cord-014597-66vd2mdu 2394 27 fraction fraction NN cord-014597-66vd2mdu 2394 28 . . . cord-014597-66vd2mdu 2395 1 Data datum NNS cord-014597-66vd2mdu 2395 2 represent represent VBP cord-014597-66vd2mdu 2395 3 one one CD cord-014597-66vd2mdu 2395 4 experiment experiment NN cord-014597-66vd2mdu 2395 5 carried carry VBN cord-014597-66vd2mdu 2395 6 out out RP cord-014597-66vd2mdu 2395 7 in in IN cord-014597-66vd2mdu 2395 8 duplicate duplicate NN cord-014597-66vd2mdu 2395 9 , , , cord-014597-66vd2mdu 2395 10 with with IN cord-014597-66vd2mdu 2395 11 random random JJ cord-014597-66vd2mdu 2395 12 experimental experimental JJ cord-014597-66vd2mdu 2395 13 error error NN cord-014597-66vd2mdu 2395 14 shown show VBN cord-014597-66vd2mdu 2395 15 . . . cord-014597-66vd2mdu 2396 1 d d LS cord-014597-66vd2mdu 2396 2 Correlogram Correlogram NNP cord-014597-66vd2mdu 2396 3 between between IN cord-014597-66vd2mdu 2396 4 the the DT cord-014597-66vd2mdu 2396 5 molecular molecular JJ cord-014597-66vd2mdu 2396 6 characteristics characteristic NNS cord-014597-66vd2mdu 2396 7 of of IN cord-014597-66vd2mdu 2396 8 the the DT cord-014597-66vd2mdu 2396 9 nano nano NN cord-014597-66vd2mdu 2396 10 - - HYPH cord-014597-66vd2mdu 2396 11 stars star NNS cord-014597-66vd2mdu 2396 12 ( ( -LRB- cord-014597-66vd2mdu 2396 13 core core NN cord-014597-66vd2mdu 2396 14 diameter diameter NN cord-014597-66vd2mdu 2396 15 , , , cord-014597-66vd2mdu 2396 16 arm arm NN cord-014597-66vd2mdu 2396 17 density density NN cord-014597-66vd2mdu 2396 18 , , , cord-014597-66vd2mdu 2396 19 arm arm NN cord-014597-66vd2mdu 2396 20 length length NN cord-014597-66vd2mdu 2396 21 , , , cord-014597-66vd2mdu 2396 22 number number NN cord-014597-66vd2mdu 2396 23 of of IN cord-014597-66vd2mdu 2396 24 monomeric monomeric JJ cord-014597-66vd2mdu 2396 25 units unit NNS cord-014597-66vd2mdu 2396 26 per per IN cord-014597-66vd2mdu 2396 27 nano nano JJ cord-014597-66vd2mdu 2396 28 - - HYPH cord-014597-66vd2mdu 2396 29 star star NN cord-014597-66vd2mdu 2396 30 ) ) -RRB- cord-014597-66vd2mdu 2396 31 , , , cord-014597-66vd2mdu 2396 32 the the DT cord-014597-66vd2mdu 2396 33 physicochemical physicochemical JJ cord-014597-66vd2mdu 2396 34 properties property NNS cord-014597-66vd2mdu 2396 35 of of IN cord-014597-66vd2mdu 2396 36 the the DT cord-014597-66vd2mdu 2396 37 corresponding correspond VBG cord-014597-66vd2mdu 2396 38 polyplexes polyplexes JJ cord-014597-66vd2mdu 2396 39 ( ( -LRB- cord-014597-66vd2mdu 2396 40 hydrodynamic hydrodynamic JJ cord-014597-66vd2mdu 2396 41 radius radius NN cord-014597-66vd2mdu 2396 42 , , , cord-014597-66vd2mdu 2396 43 zeta zeta NNP cord-014597-66vd2mdu 2396 44 potential potential NN cord-014597-66vd2mdu 2396 45 ) ) -RRB- cord-014597-66vd2mdu 2396 46 , , , cord-014597-66vd2mdu 2396 47 the the DT cord-014597-66vd2mdu 2396 48 transfection transfection NN cord-014597-66vd2mdu 2396 49 conditions condition NNS cord-014597-66vd2mdu 2396 50 ( ( -LRB- cord-014597-66vd2mdu 2396 51 N N NNP cord-014597-66vd2mdu 2396 52 / / SYM cord-014597-66vd2mdu 2396 53 P p NN cord-014597-66vd2mdu 2396 54 ratio ratio NN cord-014597-66vd2mdu 2396 55 , , , cord-014597-66vd2mdu 2396 56 amount amount NN cord-014597-66vd2mdu 2396 57 of of IN cord-014597-66vd2mdu 2396 58 polymer polymer NN cord-014597-66vd2mdu 2396 59 ) ) -RRB- cord-014597-66vd2mdu 2396 60 , , , cord-014597-66vd2mdu 2396 61 and and CC cord-014597-66vd2mdu 2396 62 the the DT cord-014597-66vd2mdu 2396 63 cellular cellular JJ cord-014597-66vd2mdu 2396 64 reactions reaction NNS cord-014597-66vd2mdu 2396 65 ( ( -LRB- cord-014597-66vd2mdu 2396 66 transfection transfection NN cord-014597-66vd2mdu 2396 67 efficiency efficiency NN cord-014597-66vd2mdu 2396 68 , , , cord-014597-66vd2mdu 2396 69 magnetism magnetism NN cord-014597-66vd2mdu 2396 70 , , . cord-014597-66vd2mdu 2397 1 viability viability NN cord-014597-66vd2mdu 2397 2 ) ) -RRB- cord-014597-66vd2mdu 2397 3 Production production NN cord-014597-66vd2mdu 2397 4 of of IN cord-014597-66vd2mdu 2397 5 recombinant recombinant JJ cord-014597-66vd2mdu 2397 6 protein protein NN cord-014597-66vd2mdu 2397 7 therapeutics therapeutic NNS cord-014597-66vd2mdu 2397 8 in in IN cord-014597-66vd2mdu 2397 9 cultivated cultivate VBN cord-014597-66vd2mdu 2397 10 mammalian mammalian JJ cord-014597-66vd2mdu 2397 11 cells cell NNS cord-014597-66vd2mdu 2397 12 Position position VBP cord-014597-66vd2mdu 2397 13 effects effect NNS cord-014597-66vd2mdu 2397 14 on on IN cord-014597-66vd2mdu 2397 15 eukaryotic eukaryotic JJ cord-014597-66vd2mdu 2397 16 gene gene NN cord-014597-66vd2mdu 2397 17 expression expression NN cord-014597-66vd2mdu 2397 18 Bacterial bacterial JJ cord-014597-66vd2mdu 2397 19 artificial artificial JJ cord-014597-66vd2mdu 2397 20 chromosome chromosome NN cord-014597-66vd2mdu 2397 21 library library NN cord-014597-66vd2mdu 2397 22 for for IN cord-014597-66vd2mdu 2397 23 genome genome NN cord-014597-66vd2mdu 2397 24 - - HYPH cord-014597-66vd2mdu 2397 25 wide wide JJ cord-014597-66vd2mdu 2397 26 analysis analysis NN cord-014597-66vd2mdu 2397 27 of of IN cord-014597-66vd2mdu 2397 28 Chinese chinese JJ cord-014597-66vd2mdu 2397 29 hamster hamster NN cord-014597-66vd2mdu 2397 30 ovary ovary NN cord-014597-66vd2mdu 2397 31 cells cell NNS cord-014597-66vd2mdu 2397 32 Construction Construction NNP cord-014597-66vd2mdu 2397 33 of of IN cord-014597-66vd2mdu 2397 34 BAC BAC NNP cord-014597-66vd2mdu 2397 35 - - HYPH cord-014597-66vd2mdu 2397 36 based base VBN cord-014597-66vd2mdu 2397 37 physical physical JJ cord-014597-66vd2mdu 2397 38 map map NN cord-014597-66vd2mdu 2397 39 and and CC cord-014597-66vd2mdu 2397 40 analysis analysis NN cord-014597-66vd2mdu 2397 41 of of IN cord-014597-66vd2mdu 2397 42 chromosome chromosome NN cord-014597-66vd2mdu 2397 43 rearrangement rearrangement NN cord-014597-66vd2mdu 2397 44 in in IN cord-014597-66vd2mdu 2397 45 Chinese chinese JJ cord-014597-66vd2mdu 2397 46 hamster hamster NN cord-014597-66vd2mdu 2397 47 ovary ovary NN cord-014597-66vd2mdu 2397 48 cell cell NN cord-014597-66vd2mdu 2397 49 lines line NNS cord-014597-66vd2mdu 2397 50 Suguru Suguru NNP cord-014597-66vd2mdu 2397 51 Imanishi Imanishi NNP cord-014597-66vd2mdu 2397 52 1 1 CD cord-014597-66vd2mdu 2397 53 , , , cord-014597-66vd2mdu 2397 54 Akira Akira NNP cord-014597-66vd2mdu 2397 55 Ito Ito NNP cord-014597-66vd2mdu 2397 56 1 1 CD cord-014597-66vd2mdu 2397 57 , , , cord-014597-66vd2mdu 2397 58 Masamichi Masamichi NNP cord-014597-66vd2mdu 2397 59 Kamihira Kamihira NNP cord-014597-66vd2mdu 2398 1 1,2 1,2 CD cord-014597-66vd2mdu 2398 2 1 1 CD cord-014597-66vd2mdu 2398 3 Department Department NNP cord-014597-66vd2mdu 2398 4 of of IN cord-014597-66vd2mdu 2398 5 Chemical Chemical NNP cord-014597-66vd2mdu 2398 6 Engineering Engineering NNP cord-014597-66vd2mdu 2398 7 Cre Cre NNP cord-014597-66vd2mdu 2398 8 recombinase recombinase NN cord-014597-66vd2mdu 2398 9 - - HYPH cord-014597-66vd2mdu 2398 10 mediated mediate VBN cord-014597-66vd2mdu 2398 11 sitespecific sitespecific NN cord-014597-66vd2mdu 2398 12 modification modification NN cord-014597-66vd2mdu 2398 13 of of IN cord-014597-66vd2mdu 2398 14 a a DT cord-014597-66vd2mdu 2398 15 cellular cellular JJ cord-014597-66vd2mdu 2398 16 genome genome NN cord-014597-66vd2mdu 2398 17 using use VBG cord-014597-66vd2mdu 2398 18 an an DT cord-014597-66vd2mdu 2398 19 integrasedefective integrasedefective JJ cord-014597-66vd2mdu 2398 20 retroviral retroviral NN cord-014597-66vd2mdu 2398 21 vector vector NN cord-014597-66vd2mdu 2398 22 Targeted target VBN cord-014597-66vd2mdu 2398 23 transgene transgene NN cord-014597-66vd2mdu 2398 24 insertion insertion NN cord-014597-66vd2mdu 2398 25 into into IN cord-014597-66vd2mdu 2398 26 the the DT cord-014597-66vd2mdu 2398 27 CHO CHO NNP cord-014597-66vd2mdu 2398 28 cell cell NN cord-014597-66vd2mdu 2398 29 genome genome NN cord-014597-66vd2mdu 2398 30 using use VBG cord-014597-66vd2mdu 2398 31 Cre Cre NNP cord-014597-66vd2mdu 2398 32 recombinase recombinase NN cord-014597-66vd2mdu 2398 33 - - HYPH cord-014597-66vd2mdu 2398 34 incorporating incorporate VBG cord-014597-66vd2mdu 2398 35 integrase integrase JJ cord-014597-66vd2mdu 2398 36 - - HYPH cord-014597-66vd2mdu 2398 37 defective defective JJ cord-014597-66vd2mdu 2398 38 retroviral retroviral NN cord-014597-66vd2mdu 2398 39 vectors vector NNS cord-014597-66vd2mdu 2398 40 An an DT cord-014597-66vd2mdu 2398 41 accumulative accumulative JJ cord-014597-66vd2mdu 2398 42 site site NN cord-014597-66vd2mdu 2398 43 - - HYPH cord-014597-66vd2mdu 2398 44 specific specific JJ cord-014597-66vd2mdu 2398 45 gene gene NN cord-014597-66vd2mdu 2398 46 integration integration NN cord-014597-66vd2mdu 2398 47 system system NN cord-014597-66vd2mdu 2398 48 using use VBG cord-014597-66vd2mdu 2398 49 Cre Cre NNP cord-014597-66vd2mdu 2398 50 recombinase recombinase NN cord-014597-66vd2mdu 2398 51 - - HYPH cord-014597-66vd2mdu 2398 52 mediated mediate VBN cord-014597-66vd2mdu 2398 53 cassette cassette NN cord-014597-66vd2mdu 2398 54 exchange exchange NN cord-014597-66vd2mdu 2398 55 Improved improve VBN cord-014597-66vd2mdu 2398 56 recombinant recombinant JJ cord-014597-66vd2mdu 2398 57 antibody antibody NN cord-014597-66vd2mdu 2398 58 production production NN cord-014597-66vd2mdu 2398 59 by by IN cord-014597-66vd2mdu 2398 60 CHO CHO NNP cord-014597-66vd2mdu 2398 61 cells cell NNS cord-014597-66vd2mdu 2398 62 using use VBG cord-014597-66vd2mdu 2398 63 a a DT cord-014597-66vd2mdu 2398 64 production production NN cord-014597-66vd2mdu 2398 65 enhancer enhancer NN cord-014597-66vd2mdu 2398 66 DNA dna NN cord-014597-66vd2mdu 2398 67 element element NN cord-014597-66vd2mdu 2398 68 with with IN cord-014597-66vd2mdu 2398 69 repeated repeat VBN cord-014597-66vd2mdu 2398 70 transgene transgene NN cord-014597-66vd2mdu 2398 71 integration integration NN cord-014597-66vd2mdu 2398 72 at at IN cord-014597-66vd2mdu 2398 73 a a DT cord-014597-66vd2mdu 2398 74 predetermined predetermine VBN cord-014597-66vd2mdu 2398 75 chromosomal chromosomal JJ cord-014597-66vd2mdu 2398 76 site site NN cord-014597-66vd2mdu 2398 77 Lipid lipid NN cord-014597-66vd2mdu 2398 78 extraction extraction NN cord-014597-66vd2mdu 2398 79 by by IN cord-014597-66vd2mdu 2398 80 methyl methyl NN cord-014597-66vd2mdu 2398 81 - - HYPH cord-014597-66vd2mdu 2398 82 tert tert NN cord-014597-66vd2mdu 2398 83 - - HYPH cord-014597-66vd2mdu 2398 84 butyl butyl NN cord-014597-66vd2mdu 2398 85 ether ether NN cord-014597-66vd2mdu 2398 86 for for IN cord-014597-66vd2mdu 2398 87 high high JJ cord-014597-66vd2mdu 2398 88 - - HYPH cord-014597-66vd2mdu 2398 89 throughput throughput NN cord-014597-66vd2mdu 2398 90 lipidomics lipidomic NNS cord-014597-66vd2mdu 2399 1 A a DT cord-014597-66vd2mdu 2399 2 simple simple JJ cord-014597-66vd2mdu 2399 3 method method NN cord-014597-66vd2mdu 2399 4 for for IN cord-014597-66vd2mdu 2399 5 the the DT cord-014597-66vd2mdu 2399 6 isolation isolation NN cord-014597-66vd2mdu 2399 7 and and CC cord-014597-66vd2mdu 2399 8 purification purification NN cord-014597-66vd2mdu 2399 9 of of IN cord-014597-66vd2mdu 2399 10 total total JJ cord-014597-66vd2mdu 2399 11 lipids lipid NNS cord-014597-66vd2mdu 2399 12 from from IN cord-014597-66vd2mdu 2399 13 animal animal NN cord-014597-66vd2mdu 2399 14 tissues tissue NNS cord-014597-66vd2mdu 2399 15 Using use VBG cord-014597-66vd2mdu 2399 16 Baculovirus Baculovirus NNP cord-014597-66vd2mdu 2399 17 as as IN cord-014597-66vd2mdu 2399 18 a a DT cord-014597-66vd2mdu 2399 19 gene gene NN cord-014597-66vd2mdu 2399 20 shuttle shuttle NN cord-014597-66vd2mdu 2399 21 in in IN cord-014597-66vd2mdu 2399 22 hMSC hmsc NN cord-014597-66vd2mdu 2399 23 : : : cord-014597-66vd2mdu 2399 24 optimization optimization NN cord-014597-66vd2mdu 2399 25 of of IN cord-014597-66vd2mdu 2399 26 transduction transduction NN cord-014597-66vd2mdu 2399 27 efficacy efficacy NN cord-014597-66vd2mdu 2399 28 Gundula Gundula NNP cord-014597-66vd2mdu 2399 29 Sprick Sprick NNP cord-014597-66vd2mdu 2399 30 1 1 CD cord-014597-66vd2mdu 2399 31 Clinical clinical JJ cord-014597-66vd2mdu 2399 32 applications application NNS cord-014597-66vd2mdu 2399 33 of of IN cord-014597-66vd2mdu 2399 34 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2399 35 stem stem NN cord-014597-66vd2mdu 2399 36 cells cell NNS cord-014597-66vd2mdu 2400 1 Concise concise JJ cord-014597-66vd2mdu 2400 2 review review NN cord-014597-66vd2mdu 2400 3 : : : cord-014597-66vd2mdu 2401 1 Mesenchymal Mesenchymal NNS cord-014597-66vd2mdu 2401 2 stem stem VBP cord-014597-66vd2mdu 2401 3 cell cell NN cord-014597-66vd2mdu 2401 4 treatment treatment NN cord-014597-66vd2mdu 2401 5 of of IN cord-014597-66vd2mdu 2401 6 the the DT cord-014597-66vd2mdu 2401 7 complications complication NNS cord-014597-66vd2mdu 2401 8 of of IN cord-014597-66vd2mdu 2401 9 diabetes diabetes NN cord-014597-66vd2mdu 2401 10 mellitus mellitus NN cord-014597-66vd2mdu 2401 11 Wharton Wharton NNP cord-014597-66vd2mdu 2401 12 's 's POS cord-014597-66vd2mdu 2401 13 Jelly Jelly NNP cord-014597-66vd2mdu 2401 14 - - HYPH cord-014597-66vd2mdu 2401 15 Derived derive VBN cord-014597-66vd2mdu 2401 16 Mesenchymal Mesenchymal NNP cord-014597-66vd2mdu 2401 17 Stromal Stromal NNP cord-014597-66vd2mdu 2401 18 Cells Cells NNP cord-014597-66vd2mdu 2401 19 as as IN cord-014597-66vd2mdu 2401 20 a a DT cord-014597-66vd2mdu 2401 21 Promising promise VBG cord-014597-66vd2mdu 2401 22 Cellular Cellular NNP cord-014597-66vd2mdu 2401 23 Therapeutic therapeutic JJ cord-014597-66vd2mdu 2401 24 Strategy Strategy NNP cord-014597-66vd2mdu 2401 25 for for IN cord-014597-66vd2mdu 2401 26 the the DT cord-014597-66vd2mdu 2401 27 Management Management NNP cord-014597-66vd2mdu 2401 28 of of IN cord-014597-66vd2mdu 2401 29 Graft graft NN cord-014597-66vd2mdu 2401 30 - - HYPH cord-014597-66vd2mdu 2401 31 versus versus IN cord-014597-66vd2mdu 2401 32 - - HYPH cord-014597-66vd2mdu 2401 33 Host Host NNP cord-014597-66vd2mdu 2401 34 Disease Disease NNP cord-014597-66vd2mdu 2401 35 Gene Gene NNP cord-014597-66vd2mdu 2401 36 therapy therapy NN cord-014597-66vd2mdu 2401 37 : : : cord-014597-66vd2mdu 2401 38 twenty twenty CD cord-014597-66vd2mdu 2401 39 - - HYPH cord-014597-66vd2mdu 2401 40 first first JJ cord-014597-66vd2mdu 2401 41 century century NN cord-014597-66vd2mdu 2401 42 medicine medicine NN cord-014597-66vd2mdu 2401 43 State state NN cord-014597-66vd2mdu 2401 44 - - HYPH cord-014597-66vd2mdu 2401 45 of of IN cord-014597-66vd2mdu 2401 46 - - HYPH cord-014597-66vd2mdu 2401 47 the the DT cord-014597-66vd2mdu 2401 48 - - HYPH cord-014597-66vd2mdu 2401 49 art art NN cord-014597-66vd2mdu 2401 50 gene gene NN cord-014597-66vd2mdu 2401 51 - - HYPH cord-014597-66vd2mdu 2401 52 based base VBN cord-014597-66vd2mdu 2401 53 therapies therapy NNS cord-014597-66vd2mdu 2401 54 : : : cord-014597-66vd2mdu 2402 1 the the DT cord-014597-66vd2mdu 2402 2 road road NN cord-014597-66vd2mdu 2402 3 ahead ahead RB cord-014597-66vd2mdu 2402 4 Viral viral JJ cord-014597-66vd2mdu 2402 5 vectors vector NNS cord-014597-66vd2mdu 2402 6 : : : cord-014597-66vd2mdu 2402 7 a a DT cord-014597-66vd2mdu 2402 8 look look NN cord-014597-66vd2mdu 2402 9 back back RB cord-014597-66vd2mdu 2402 10 and and CC cord-014597-66vd2mdu 2402 11 ahead ahead RB cord-014597-66vd2mdu 2402 12 on on IN cord-014597-66vd2mdu 2402 13 gene gene NN cord-014597-66vd2mdu 2402 14 transfer transfer NN cord-014597-66vd2mdu 2402 15 technology technology NN cord-014597-66vd2mdu 2402 16 Basic basic JJ cord-014597-66vd2mdu 2402 17 Biology Biology NNP cord-014597-66vd2mdu 2402 18 of of IN cord-014597-66vd2mdu 2402 19 Adeno Adeno NNP cord-014597-66vd2mdu 2402 20 - - HYPH cord-014597-66vd2mdu 2402 21 Associated Associated NNP cord-014597-66vd2mdu 2402 22 Virus Virus NNP cord-014597-66vd2mdu 2402 23 ( ( -LRB- cord-014597-66vd2mdu 2402 24 AAV AAV NNP cord-014597-66vd2mdu 2402 25 ) ) -RRB- cord-014597-66vd2mdu 2402 26 Vectors Vectors NNP cord-014597-66vd2mdu 2402 27 Used use VBN cord-014597-66vd2mdu 2402 28 in in IN cord-014597-66vd2mdu 2402 29 Gene Gene NNP cord-014597-66vd2mdu 2402 30 Therapy Therapy NNP cord-014597-66vd2mdu 2402 31 Biosafety Biosafety NNP cord-014597-66vd2mdu 2402 32 challenges challenge VBZ cord-014597-66vd2mdu 2402 33 for for IN cord-014597-66vd2mdu 2402 34 use use NN cord-014597-66vd2mdu 2402 35 of of IN cord-014597-66vd2mdu 2402 36 lentiviral lentiviral JJ cord-014597-66vd2mdu 2402 37 vectors vector NNS cord-014597-66vd2mdu 2402 38 in in IN cord-014597-66vd2mdu 2402 39 gene gene NN cord-014597-66vd2mdu 2402 40 therapy therapy NN cord-014597-66vd2mdu 2402 41 Adenoviral Adenoviral NNP cord-014597-66vd2mdu 2402 42 vector vector NN cord-014597-66vd2mdu 2402 43 - - HYPH cord-014597-66vd2mdu 2402 44 mediated mediate VBN cord-014597-66vd2mdu 2402 45 gene gene NN cord-014597-66vd2mdu 2402 46 therapy therapy NN cord-014597-66vd2mdu 2402 47 for for IN cord-014597-66vd2mdu 2402 48 gliomas glioma NNS cord-014597-66vd2mdu 2402 49 : : : cord-014597-66vd2mdu 2403 1 coming come VBG cord-014597-66vd2mdu 2403 2 of of IN cord-014597-66vd2mdu 2403 3 age age NN cord-014597-66vd2mdu 2403 4 Manufacturing manufacturing NN cord-014597-66vd2mdu 2403 5 of of IN cord-014597-66vd2mdu 2403 6 viral viral JJ cord-014597-66vd2mdu 2403 7 vectors vector NNS cord-014597-66vd2mdu 2403 8 for for IN cord-014597-66vd2mdu 2403 9 gene gene NN cord-014597-66vd2mdu 2403 10 therapy therapy NN cord-014597-66vd2mdu 2403 11 : : : cord-014597-66vd2mdu 2404 1 part part NN cord-014597-66vd2mdu 2404 2 I. I. NNP cord-014597-66vd2mdu 2404 3 Upstream Upstream NNP cord-014597-66vd2mdu 2404 4 processing process VBG cord-014597-66vd2mdu 2404 5 The the DT cord-014597-66vd2mdu 2404 6 complete complete JJ cord-014597-66vd2mdu 2404 7 DNA dna NN cord-014597-66vd2mdu 2404 8 sequence sequence NN cord-014597-66vd2mdu 2404 9 of of IN cord-014597-66vd2mdu 2404 10 Autographa Autographa NNP cord-014597-66vd2mdu 2404 11 californica californica NNP cord-014597-66vd2mdu 2404 12 nuclear nuclear JJ cord-014597-66vd2mdu 2404 13 polyhedrosis polyhedrosis NN cord-014597-66vd2mdu 2404 14 virus virus NN cord-014597-66vd2mdu 2404 15 Efficient efficient JJ cord-014597-66vd2mdu 2404 16 gene gene NN cord-014597-66vd2mdu 2404 17 transfer transfer NN cord-014597-66vd2mdu 2404 18 into into IN cord-014597-66vd2mdu 2404 19 human human JJ cord-014597-66vd2mdu 2404 20 hepatocytes hepatocyte NNS cord-014597-66vd2mdu 2404 21 by by IN cord-014597-66vd2mdu 2404 22 baculovirus baculovirus NN cord-014597-66vd2mdu 2404 23 vectors vector NNS cord-014597-66vd2mdu 2404 24 Efficient Efficient NNP cord-014597-66vd2mdu 2404 25 Transduction Transduction NNP cord-014597-66vd2mdu 2404 26 of of IN cord-014597-66vd2mdu 2404 27 Mammalian mammalian JJ cord-014597-66vd2mdu 2404 28 Cells Cells NNPS cord-014597-66vd2mdu 2404 29 by by IN cord-014597-66vd2mdu 2404 30 a a DT cord-014597-66vd2mdu 2404 31 Recombinant Recombinant NNP cord-014597-66vd2mdu 2404 32 Baculovirus Baculovirus NNP cord-014597-66vd2mdu 2404 33 Having have VBG cord-014597-66vd2mdu 2404 34 the the DT cord-014597-66vd2mdu 2404 35 Vesicular Vesicular NNP cord-014597-66vd2mdu 2404 36 Stomatitis Stomatitis NNP cord-014597-66vd2mdu 2404 37 Virus Virus NNP cord-014597-66vd2mdu 2404 38 G g NN cord-014597-66vd2mdu 2404 39 Glycoprotein glycoprotein NN cord-014597-66vd2mdu 2404 40 Recombinant recombinant JJ cord-014597-66vd2mdu 2404 41 baculoviruses baculoviruse NNS cord-014597-66vd2mdu 2404 42 as as IN cord-014597-66vd2mdu 2404 43 mammalian mammalian JJ cord-014597-66vd2mdu 2404 44 cell cell NN cord-014597-66vd2mdu 2404 45 gene gene NN cord-014597-66vd2mdu 2404 46 - - HYPH cord-014597-66vd2mdu 2404 47 delivery delivery NN cord-014597-66vd2mdu 2404 48 vectors vector NNS cord-014597-66vd2mdu 2405 1 Post post JJ cord-014597-66vd2mdu 2405 2 - - JJ cord-014597-66vd2mdu 2405 3 transcriptional transcriptional JJ cord-014597-66vd2mdu 2405 4 regulatory regulatory JJ cord-014597-66vd2mdu 2405 5 element element NN cord-014597-66vd2mdu 2405 6 boosts boost VBZ cord-014597-66vd2mdu 2405 7 baculovirusmediated baculovirusmediated JJ cord-014597-66vd2mdu 2405 8 gene gene NN cord-014597-66vd2mdu 2405 9 expression expression NN cord-014597-66vd2mdu 2405 10 in in IN cord-014597-66vd2mdu 2405 11 vertebrate vertebrate JJ cord-014597-66vd2mdu 2405 12 cells cell NNS cord-014597-66vd2mdu 2406 1 Baculoviral Baculoviral NNP cord-014597-66vd2mdu 2406 2 Vector Vector NNP cord-014597-66vd2mdu 2406 3 - - HYPH cord-014597-66vd2mdu 2406 4 Mediated mediate VBN cord-014597-66vd2mdu 2406 5 Transient Transient NNP cord-014597-66vd2mdu 2406 6 and and CC cord-014597-66vd2mdu 2406 7 Stable stable JJ cord-014597-66vd2mdu 2406 8 Transgene transgene NN cord-014597-66vd2mdu 2406 9 Expression expression NN cord-014597-66vd2mdu 2406 10 in in IN cord-014597-66vd2mdu 2406 11 Human Human NNP cord-014597-66vd2mdu 2406 12 Embryonic Embryonic NNP cord-014597-66vd2mdu 2406 13 Stem stem NN cord-014597-66vd2mdu 2406 14 Cells cell NNS cord-014597-66vd2mdu 2407 1 Systematic systematic JJ cord-014597-66vd2mdu 2407 2 comparison comparison NN cord-014597-66vd2mdu 2407 3 of of IN cord-014597-66vd2mdu 2407 4 constitutive constitutive JJ cord-014597-66vd2mdu 2407 5 promoters promoter NNS cord-014597-66vd2mdu 2407 6 and and CC cord-014597-66vd2mdu 2407 7 the the DT cord-014597-66vd2mdu 2407 8 doxycycline doxycycline NN cord-014597-66vd2mdu 2407 9 - - HYPH cord-014597-66vd2mdu 2407 10 inducible inducible JJ cord-014597-66vd2mdu 2407 11 promoter promoter NN cord-014597-66vd2mdu 2407 12 Baculovirus Baculovirus NNP cord-014597-66vd2mdu 2407 13 - - HYPH cord-014597-66vd2mdu 2407 14 induced induce VBN cord-014597-66vd2mdu 2407 15 recombinant recombinant JJ cord-014597-66vd2mdu 2407 16 protein protein NN cord-014597-66vd2mdu 2407 17 expression expression NN cord-014597-66vd2mdu 2407 18 in in IN cord-014597-66vd2mdu 2407 19 human human JJ cord-014597-66vd2mdu 2407 20 mesenchymal mesenchymal JJ cord-014597-66vd2mdu 2407 21 stromal stromal JJ cord-014597-66vd2mdu 2407 22 stem stem NN cord-014597-66vd2mdu 2407 23 cells cell NNS cord-014597-66vd2mdu 2407 24 : : : cord-014597-66vd2mdu 2407 25 A a DT cord-014597-66vd2mdu 2407 26 promoter promoter NN cord-014597-66vd2mdu 2407 27 study study NN cord-014597-66vd2mdu 2407 28 Triple Triple NNP cord-014597-66vd2mdu 2407 29 - - HYPH cord-014597-66vd2mdu 2407 30 Negative negative JJ cord-014597-66vd2mdu 2407 31 Breast Breast NNP cord-014597-66vd2mdu 2407 32 Cancer Cancer NNP cord-014597-66vd2mdu 2407 33 : : : cord-014597-66vd2mdu 2408 1 An an DT cord-014597-66vd2mdu 2408 2 Unmet unmet JJ cord-014597-66vd2mdu 2408 3 Medical Medical NNP cord-014597-66vd2mdu 2408 4 Need need NN cord-014597-66vd2mdu 2408 5 The the DT cord-014597-66vd2mdu 2408 6 therapeutic therapeutic JJ cord-014597-66vd2mdu 2408 7 monoclonal monoclonal JJ cord-014597-66vd2mdu 2408 8 antibody antibody NN cord-014597-66vd2mdu 2408 9 market market NN cord-014597-66vd2mdu 2408 10 . . . cord-014597-66vd2mdu 2409 1 mabs mabs NNP cord-014597-66vd2mdu 2409 2 A a DT cord-014597-66vd2mdu 2409 3 monoclonal monoclonal JJ cord-014597-66vd2mdu 2409 4 Antibody Antibody NNP cord-014597-66vd2mdu 2409 5 against against IN cord-014597-66vd2mdu 2409 6 Human Human NNP cord-014597-66vd2mdu 2409 7 Notch1 Notch1 NNP cord-014597-66vd2mdu 2409 8 Ligand Ligand NNP cord-014597-66vd2mdu 2409 9 - - HYPH cord-014597-66vd2mdu 2409 10 Binding Binding NNP cord-014597-66vd2mdu 2409 11 Domain Domain NNP cord-014597-66vd2mdu 2409 12 Depletes deplete VBZ cord-014597-66vd2mdu 2409 13 Subpopulation Subpopulation NNP cord-014597-66vd2mdu 2409 14 of of IN cord-014597-66vd2mdu 2409 15 Putative Putative NNP cord-014597-66vd2mdu 2409 16 Breast Breast NNP cord-014597-66vd2mdu 2409 17 Cancer Cancer NNP cord-014597-66vd2mdu 2410 1 Stem stem NN cord-014597-66vd2mdu 2410 2 - - HYPH cord-014597-66vd2mdu 2410 3 like like JJ cord-014597-66vd2mdu 2410 4 Cells cell NNS cord-014597-66vd2mdu 2410 5 Notch Notch NNP cord-014597-66vd2mdu 2410 6 activation activation NN cord-014597-66vd2mdu 2410 7 stimulates stimulate VBZ cord-014597-66vd2mdu 2410 8 migration migration NN cord-014597-66vd2mdu 2410 9 of of IN cord-014597-66vd2mdu 2410 10 breast breast NN cord-014597-66vd2mdu 2410 11 cancer cancer NN cord-014597-66vd2mdu 2410 12 cells cell NNS cord-014597-66vd2mdu 2410 13 and and CC cord-014597-66vd2mdu 2410 14 promotes promote VBZ cord-014597-66vd2mdu 2410 15 tumor tumor NN cord-014597-66vd2mdu 2410 16 growth growth NN cord-014597-66vd2mdu 2410 17 Notch notch NN cord-014597-66vd2mdu 2410 18 - - HYPH cord-014597-66vd2mdu 2410 19 out out NN cord-014597-66vd2mdu 2410 20 for for IN cord-014597-66vd2mdu 2410 21 breast breast NN cord-014597-66vd2mdu 2410 22 cancer cancer NN cord-014597-66vd2mdu 2410 23 therapies therapy NNS cord-014597-66vd2mdu 2411 1 AAV AAV NNP cord-014597-66vd2mdu 2411 2 production production NN cord-014597-66vd2mdu 2411 3 in in IN cord-014597-66vd2mdu 2411 4 suspension suspension NN cord-014597-66vd2mdu 2411 5 : : : cord-014597-66vd2mdu 2411 6 evaluation evaluation NN cord-014597-66vd2mdu 2411 7 of of IN cord-014597-66vd2mdu 2411 8 different different JJ cord-014597-66vd2mdu 2411 9 cell cell NN cord-014597-66vd2mdu 2411 10 culture culture NN cord-014597-66vd2mdu 2411 11 media medium NNS cord-014597-66vd2mdu 2411 12 and and CC cord-014597-66vd2mdu 2411 13 scale scale NN cord-014597-66vd2mdu 2411 14 - - HYPH cord-014597-66vd2mdu 2411 15 up up NN cord-014597-66vd2mdu 2411 16 potential potential JJ cord-014597-66vd2mdu 2411 17 Modular modular JJ cord-014597-66vd2mdu 2411 18 adeno adeno NN cord-014597-66vd2mdu 2411 19 - - HYPH cord-014597-66vd2mdu 2411 20 associated associate VBN cord-014597-66vd2mdu 2411 21 virus virus NN cord-014597-66vd2mdu 2411 22 ( ( -LRB- cord-014597-66vd2mdu 2411 23 rAAV rAAV NNP cord-014597-66vd2mdu 2411 24 ) ) -RRB- cord-014597-66vd2mdu 2411 25 vectors vector NNS cord-014597-66vd2mdu 2411 26 used use VBN cord-014597-66vd2mdu 2411 27 for for IN cord-014597-66vd2mdu 2411 28 cellular cellular JJ cord-014597-66vd2mdu 2411 29 virusdirected virusdirected JJ cord-014597-66vd2mdu 2411 30 enzyme enzyme NN cord-014597-66vd2mdu 2411 31 prodrug prodrug NN cord-014597-66vd2mdu 2411 32 therapy therapy NN cord-014597-66vd2mdu 2411 33 Production production NN cord-014597-66vd2mdu 2411 34 of of IN cord-014597-66vd2mdu 2411 35 Recombinant Recombinant NNP cord-014597-66vd2mdu 2411 36 Adenoassociated Adenoassociated NNP cord-014597-66vd2mdu 2411 37 Virus Virus NNP cord-014597-66vd2mdu 2411 38 Vectors vector NNS cord-014597-66vd2mdu 2411 39 Using use VBG cord-014597-66vd2mdu 2411 40 Suspension Suspension NNP cord-014597-66vd2mdu 2411 41 HEK293 HEK293 NNP cord-014597-66vd2mdu 2411 42 Cells Cells NNPS cord-014597-66vd2mdu 2411 43 and and CC cord-014597-66vd2mdu 2411 44 Continuous continuous JJ cord-014597-66vd2mdu 2411 45 Harvest Harvest NNP cord-014597-66vd2mdu 2411 46 of of IN cord-014597-66vd2mdu 2411 47 Vector Vector NNP cord-014597-66vd2mdu 2411 48 From from IN cord-014597-66vd2mdu 2411 49 the the DT cord-014597-66vd2mdu 2411 50 Culture Culture NNP cord-014597-66vd2mdu 2411 51 Media medium NNS cord-014597-66vd2mdu 2411 52 for for IN cord-014597-66vd2mdu 2411 53 GMP GMP NNP cord-014597-66vd2mdu 2411 54 FIX FIX NNP cord-014597-66vd2mdu 2411 55 and and CC cord-014597-66vd2mdu 2411 56 FLT1 FLT1 NNP cord-014597-66vd2mdu 2411 57 Clinical Clinical NNP cord-014597-66vd2mdu 2411 58 Vector Vector NNP cord-014597-66vd2mdu 2411 59 Development Development NNP cord-014597-66vd2mdu 2411 60 of of IN cord-014597-66vd2mdu 2411 61 a a DT cord-014597-66vd2mdu 2411 62 cost cost NN cord-014597-66vd2mdu 2411 63 - - HYPH cord-014597-66vd2mdu 2411 64 efficient efficient JJ cord-014597-66vd2mdu 2411 65 scalable scalable JJ cord-014597-66vd2mdu 2411 66 production production NN cord-014597-66vd2mdu 2411 67 process process NN cord-014597-66vd2mdu 2411 68 for for IN cord-014597-66vd2mdu 2411 69 RAAV-8 RAAV-8 NNP cord-014597-66vd2mdu 2411 70 based base VBN cord-014597-66vd2mdu 2411 71 gene gene NN cord-014597-66vd2mdu 2411 72 therapy therapy NN cord-014597-66vd2mdu 2411 73 by by IN cord-014597-66vd2mdu 2411 74 transfection transfection NN cord-014597-66vd2mdu 2411 75 of of IN cord-014597-66vd2mdu 2411 76 Hek-293 Hek-293 NNP cord-014597-66vd2mdu 2411 77 cells cell NNS cord-014597-66vd2mdu 2411 78 Simon Simon NNP cord-014597-66vd2mdu 2411 79 Arias Arias NNP cord-014597-66vd2mdu 2411 80 2 2 CD cord-014597-66vd2mdu 2411 81 , , , cord-014597-66vd2mdu 2411 82 Mustapha Mustapha NNP cord-014597-66vd2mdu 2411 83 Hohoud Hohoud NNP cord-014597-66vd2mdu 2411 84 1 1 CD cord-014597-66vd2mdu 2411 85 , , , cord-014597-66vd2mdu 2411 86 Roel Roel NNP cord-014597-66vd2mdu 2411 87 Lievrouw Lievrouw NNP cord-014597-66vd2mdu 2411 88 1 1 CD cord-014597-66vd2mdu 2411 89 , , , cord-014597-66vd2mdu 2411 90 Fabien Fabien NNP cord-014597-66vd2mdu 2411 91 Moncaubeig Moncaubeig NNP cord-014597-66vd2mdu 2411 92 1 1 CD cord-014597-66vd2mdu 2412 1 B-1120 B-1120 NNP cord-014597-66vd2mdu 2412 2 Brussels Brussels NNP cord-014597-66vd2mdu 2412 3 , , , cord-014597-66vd2mdu 2412 4 Belgium Belgium NNP cord-014597-66vd2mdu 2412 5 ; ; : cord-014597-66vd2mdu 2412 6 2 2 CD cord-014597-66vd2mdu 2412 7 Généthon Généthon NNP cord-014597-66vd2mdu 2412 8 , , , cord-014597-66vd2mdu 2412 9 Rue Rue NNP cord-014597-66vd2mdu 2412 10 de de NNP cord-014597-66vd2mdu 2412 11 l'Internationale l'Internationale NNP cord-014597-66vd2mdu 2412 12 1 1 CD cord-014597-66vd2mdu 2412 13 Cell Cell NNP cord-014597-66vd2mdu 2412 14 - - HYPH cord-014597-66vd2mdu 2412 15 Free Free NNP cord-014597-66vd2mdu 2412 16 Systems Systems NNPS cord-014597-66vd2mdu 2412 17 Based base VBN cord-014597-66vd2mdu 2412 18 on on IN cord-014597-66vd2mdu 2412 19 CHO CHO NNP cord-014597-66vd2mdu 2412 20 Cell Cell NNP cord-014597-66vd2mdu 2412 21 Lysates Lysates NNP cord-014597-66vd2mdu 2412 22 : : : cord-014597-66vd2mdu 2413 1 Optimization Optimization NNP cord-014597-66vd2mdu 2413 2 Strategies Strategies NNPS cord-014597-66vd2mdu 2413 3 , , , cord-014597-66vd2mdu 2413 4 Synthesis Synthesis NNP cord-014597-66vd2mdu 2413 5 of of IN cord-014597-66vd2mdu 2413 6 " " `` cord-014597-66vd2mdu 2413 7 Difficult difficult JJ cord-014597-66vd2mdu 2413 8 - - HYPH cord-014597-66vd2mdu 2413 9 to to IN cord-014597-66vd2mdu 2413 10 - - HYPH cord-014597-66vd2mdu 2413 11 Express Express NNP cord-014597-66vd2mdu 2413 12 " " `` cord-014597-66vd2mdu 2413 13 Proteins Proteins NNPS cord-014597-66vd2mdu 2413 14 and and CC cord-014597-66vd2mdu 2413 15 Future Future NNP cord-014597-66vd2mdu 2413 16 Perspectives Perspectives NNPS cord-014597-66vd2mdu 2413 17 Cell cell NN cord-014597-66vd2mdu 2413 18 - - HYPH cord-014597-66vd2mdu 2413 19 free free JJ cord-014597-66vd2mdu 2413 20 protein protein NN cord-014597-66vd2mdu 2413 21 expression expression NN cord-014597-66vd2mdu 2413 22 based base VBN cord-014597-66vd2mdu 2413 23 on on IN cord-014597-66vd2mdu 2413 24 extracts extract NNS cord-014597-66vd2mdu 2413 25 from from IN cord-014597-66vd2mdu 2413 26 CHO CHO NNP cord-014597-66vd2mdu 2413 27 cells cell NNS cord-014597-66vd2mdu 2413 28 Comparison comparison NN cord-014597-66vd2mdu 2413 29 of of IN cord-014597-66vd2mdu 2413 30 cell cell NN cord-014597-66vd2mdu 2413 31 - - HYPH cord-014597-66vd2mdu 2413 32 based base VBN cord-014597-66vd2mdu 2413 33 vs. vs. IN cord-014597-66vd2mdu 2413 34 cell cell NN cord-014597-66vd2mdu 2413 35 - - HYPH cord-014597-66vd2mdu 2413 36 free free JJ cord-014597-66vd2mdu 2413 37 mammalian mammalian JJ cord-014597-66vd2mdu 2413 38 systems system NNS cord-014597-66vd2mdu 2413 39 for for IN cord-014597-66vd2mdu 2413 40 the the DT cord-014597-66vd2mdu 2413 41 production production NN cord-014597-66vd2mdu 2413 42 of of IN cord-014597-66vd2mdu 2413 43 a a DT cord-014597-66vd2mdu 2413 44 recombinant recombinant JJ cord-014597-66vd2mdu 2413 45 human human JJ cord-014597-66vd2mdu 2413 46 bone bone NN cord-014597-66vd2mdu 2413 47 morphogenic morphogenic JJ cord-014597-66vd2mdu 2413 48 growth growth NN cord-014597-66vd2mdu 2413 49 factor factor NN cord-014597-66vd2mdu 2413 50 IRES IRES NNP cord-014597-66vd2mdu 2413 51 - - HYPH cord-014597-66vd2mdu 2413 52 Mediated mediate VBN cord-014597-66vd2mdu 2413 53 Translation translation NN cord-014597-66vd2mdu 2413 54 of of IN cord-014597-66vd2mdu 2413 55 Membrane Membrane NNP cord-014597-66vd2mdu 2413 56 Proteins Proteins NNPS cord-014597-66vd2mdu 2413 57 and and CC cord-014597-66vd2mdu 2413 58 Glycoproteins Glycoproteins NNPS cord-014597-66vd2mdu 2413 59 in in IN cord-014597-66vd2mdu 2413 60 Production production NN cord-014597-66vd2mdu 2413 61 of of IN cord-014597-66vd2mdu 2413 62 recombinant recombinant JJ cord-014597-66vd2mdu 2413 63 factor factor NN cord-014597-66vd2mdu 2413 64 VII vii NN cord-014597-66vd2mdu 2413 65 in in IN cord-014597-66vd2mdu 2413 66 Sk Sk NNP cord-014597-66vd2mdu 2413 67 - - HYPH cord-014597-66vd2mdu 2413 68 Hep-1 Hep-1 NNP cord-014597-66vd2mdu 2413 69 human human JJ cord-014597-66vd2mdu 2413 70 cell cell NN cord-014597-66vd2mdu 2413 71 line line NN cord-014597-66vd2mdu 2413 72 ZIP zip NN cord-014597-66vd2mdu 2413 73 14049 14049 CD cord-014597-66vd2mdu 2413 74 - - SYM cord-014597-66vd2mdu 2413 75 900 900 CD cord-014597-66vd2mdu 2413 76 , , , cord-014597-66vd2mdu 2413 77 Brazil Brazil NNP cord-014597-66vd2mdu 2413 78 ; ; : cord-014597-66vd2mdu 2413 79 3 3 CD cord-014597-66vd2mdu 2413 80 Department Department NNP cord-014597-66vd2mdu 2413 81 of of IN cord-014597-66vd2mdu 2413 82 Clinical Clinical NNP cord-014597-66vd2mdu 2413 83 , , , cord-014597-66vd2mdu 2413 84 Toxicological toxicological JJ cord-014597-66vd2mdu 2413 85 and and CC cord-014597-66vd2mdu 2413 86 Food Food NNP cord-014597-66vd2mdu 2413 87 Science Science NNP cord-014597-66vd2mdu 2413 88 Analysis Analysis NNP cord-014597-66vd2mdu 2413 89 , , , cord-014597-66vd2mdu 2413 90 Faculty Faculty NNP cord-014597-66vd2mdu 2413 91 of of IN cord-014597-66vd2mdu 2413 92 Pharmaceutical Pharmaceutical NNP cord-014597-66vd2mdu 2413 93 Sciences Sciences NNPS cord-014597-66vd2mdu 2413 94 of of IN cord-014597-66vd2mdu 2413 95 Ribeirão Ribeirão NNP cord-014597-66vd2mdu 2413 96 Preto Preto NNP cord-014597-66vd2mdu 2413 97 Human Human NNP cord-014597-66vd2mdu 2413 98 cell cell NN cord-014597-66vd2mdu 2413 99 lines line NNS cord-014597-66vd2mdu 2413 100 for for IN cord-014597-66vd2mdu 2413 101 the the DT cord-014597-66vd2mdu 2413 102 production production NN cord-014597-66vd2mdu 2413 103 of of IN cord-014597-66vd2mdu 2413 104 recombinant recombinant JJ cord-014597-66vd2mdu 2413 105 proteins protein NNS cord-014597-66vd2mdu 2413 106 : : : cord-014597-66vd2mdu 2413 107 on on IN cord-014597-66vd2mdu 2413 108 the the DT cord-014597-66vd2mdu 2413 109 horizon horizon NN cord-014597-66vd2mdu 2413 110 Production Production NNP cord-014597-66vd2mdu 2413 111 of of IN cord-014597-66vd2mdu 2413 112 recombinant recombinant JJ cord-014597-66vd2mdu 2413 113 protein protein NN cord-014597-66vd2mdu 2413 114 therapeutics therapeutic NNS cord-014597-66vd2mdu 2413 115 in in IN cord-014597-66vd2mdu 2413 116 cultivated cultivate VBN cord-014597-66vd2mdu 2413 117 mammalian mammalian JJ cord-014597-66vd2mdu 2413 118 cells cell NNS cord-014597-66vd2mdu 2414 1 Recombinant recombinant JJ cord-014597-66vd2mdu 2414 2 protein protein NN cord-014597-66vd2mdu 2414 3 therapeutics therapeutic NNS cord-014597-66vd2mdu 2414 4 from from IN cord-014597-66vd2mdu 2414 5 cho cho NNP cord-014597-66vd2mdu 2414 6 cells cell NNS cord-014597-66vd2mdu 2414 7 -20 -20 CD cord-014597-66vd2mdu 2414 8 years year NNS cord-014597-66vd2mdu 2414 9 and and CC cord-014597-66vd2mdu 2414 10 counting count VBG cord-014597-66vd2mdu 2414 11 Establishment Establishment NNP cord-014597-66vd2mdu 2414 12 of of IN cord-014597-66vd2mdu 2414 13 a a DT cord-014597-66vd2mdu 2414 14 cell cell NN cord-014597-66vd2mdu 2414 15 line line NN cord-014597-66vd2mdu 2414 16 expressing express VBG cord-014597-66vd2mdu 2414 17 recombinant recombinant JJ cord-014597-66vd2mdu 2414 18 factor factor NN cord-014597-66vd2mdu 2414 19 VII vii NN cord-014597-66vd2mdu 2414 20 and and CC cord-014597-66vd2mdu 2414 21 its -PRON- PRP$ cord-014597-66vd2mdu 2414 22 subsequent subsequent JJ cord-014597-66vd2mdu 2414 23 conversion conversion NN cord-014597-66vd2mdu 2414 24 to to IN cord-014597-66vd2mdu 2414 25 active active JJ cord-014597-66vd2mdu 2414 26 form form NN cord-014597-66vd2mdu 2414 27 FVIIa FVIIa NNS cord-014597-66vd2mdu 2414 28 through through IN cord-014597-66vd2mdu 2414 29 hepsin hepsin NNP cord-014597-66vd2mdu 2414 30 by by IN cord-014597-66vd2mdu 2414 31 genetic genetic JJ cord-014597-66vd2mdu 2414 32 engineering engineering NN cord-014597-66vd2mdu 2414 33 method method NN cord-014597-66vd2mdu 2414 34 Expression expression NN cord-014597-66vd2mdu 2414 35 and and CC cord-014597-66vd2mdu 2414 36 fast fast JJ cord-014597-66vd2mdu 2414 37 preparation preparation NN cord-014597-66vd2mdu 2414 38 of of IN cord-014597-66vd2mdu 2414 39 biologically biologically RB cord-014597-66vd2mdu 2414 40 active active JJ cord-014597-66vd2mdu 2414 41 recombinant recombinant JJ cord-014597-66vd2mdu 2414 42 human human JJ cord-014597-66vd2mdu 2414 43 coagulation coagulation NN cord-014597-66vd2mdu 2414 44 factor factor NN cord-014597-66vd2mdu 2414 45 VII vii NN cord-014597-66vd2mdu 2414 46 in in IN cord-014597-66vd2mdu 2414 47 CHO CHO NNP cord-014597-66vd2mdu 2414 48 - - HYPH cord-014597-66vd2mdu 2414 49 K1 K1 NNP cord-014597-66vd2mdu 2414 50 cells cell NNS cord-014597-66vd2mdu 2414 51 Implications implication NNS cord-014597-66vd2mdu 2414 52 of of IN cord-014597-66vd2mdu 2414 53 the the DT cord-014597-66vd2mdu 2414 54 presence presence NN cord-014597-66vd2mdu 2414 55 of of IN cord-014597-66vd2mdu 2414 56 N N NNP cord-014597-66vd2mdu 2414 57 - - HYPH cord-014597-66vd2mdu 2414 58 glycolylneuraminic glycolylneuraminic NN cord-014597-66vd2mdu 2414 59 acid acid NN cord-014597-66vd2mdu 2414 60 in in IN cord-014597-66vd2mdu 2414 61 recombinant recombinant JJ cord-014597-66vd2mdu 2414 62 therapeutic therapeutic JJ cord-014597-66vd2mdu 2414 63 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 2415 1 Uniquely uniquely RB cord-014597-66vd2mdu 2415 2 human human JJ cord-014597-66vd2mdu 2415 3 evolution evolution NN cord-014597-66vd2mdu 2415 4 of of IN cord-014597-66vd2mdu 2415 5 sialic sialic JJ cord-014597-66vd2mdu 2415 6 acid acid NN cord-014597-66vd2mdu 2415 7 genetics genetic NNS cord-014597-66vd2mdu 2415 8 and and CC cord-014597-66vd2mdu 2415 9 biology biology NN cord-014597-66vd2mdu 2415 10 Production production NN cord-014597-66vd2mdu 2415 11 platforms platform NNS cord-014597-66vd2mdu 2415 12 for for IN cord-014597-66vd2mdu 2415 13 biotherapeutic biotherapeutic JJ cord-014597-66vd2mdu 2415 14 glycoproteins glycoprotein NNS cord-014597-66vd2mdu 2415 15 . . . cord-014597-66vd2mdu 2416 1 Occurrence occurrence NN cord-014597-66vd2mdu 2416 2 , , , cord-014597-66vd2mdu 2416 3 impact impact NN cord-014597-66vd2mdu 2416 4 , , , cord-014597-66vd2mdu 2416 5 and and CC cord-014597-66vd2mdu 2416 6 challenges challenge NNS cord-014597-66vd2mdu 2416 7 of of IN cord-014597-66vd2mdu 2416 8 non non JJ cord-014597-66vd2mdu 2416 9 - - JJ cord-014597-66vd2mdu 2416 10 human human JJ cord-014597-66vd2mdu 2416 11 sialylation sialylation NN cord-014597-66vd2mdu 2416 12 Human Human NNP cord-014597-66vd2mdu 2416 13 cells cell NNS cord-014597-66vd2mdu 2416 14 : : : cord-014597-66vd2mdu 2416 15 new new JJ cord-014597-66vd2mdu 2416 16 platform platform NN cord-014597-66vd2mdu 2416 17 for for IN cord-014597-66vd2mdu 2416 18 recombinant recombinant JJ cord-014597-66vd2mdu 2416 19 therapeutic therapeutic JJ cord-014597-66vd2mdu 2416 20 protein protein NN cord-014597-66vd2mdu 2416 21 production production NN cord-014597-66vd2mdu 2416 22 Therapeutic therapeutic JJ cord-014597-66vd2mdu 2416 23 glycoprotein glycoprotein NN cord-014597-66vd2mdu 2416 24 production production NN cord-014597-66vd2mdu 2416 25 in in IN cord-014597-66vd2mdu 2416 26 mammalian mammalian JJ cord-014597-66vd2mdu 2416 27 cells cell NNS cord-014597-66vd2mdu 2417 1 Masthering masthere VBG cord-014597-66vd2mdu 2417 2 industrialization industrialization NN cord-014597-66vd2mdu 2417 3 of of IN cord-014597-66vd2mdu 2417 4 cell cell NN cord-014597-66vd2mdu 2417 5 therapy therapy NN cord-014597-66vd2mdu 2417 6 products product NNS cord-014597-66vd2mdu 2418 1 Tissue tissue NN cord-014597-66vd2mdu 2418 2 cells cell NNS cord-014597-66vd2mdu 2418 3 feel feel VBP cord-014597-66vd2mdu 2418 4 and and CC cord-014597-66vd2mdu 2418 5 respond respond VBP cord-014597-66vd2mdu 2418 6 to to IN cord-014597-66vd2mdu 2418 7 the the DT cord-014597-66vd2mdu 2418 8 stiffness stiffness NN cord-014597-66vd2mdu 2418 9 of of IN cord-014597-66vd2mdu 2418 10 their -PRON- PRP$ cord-014597-66vd2mdu 2418 11 substrate substrate NN cord-014597-66vd2mdu 2418 12 Matrix Matrix NNP cord-014597-66vd2mdu 2418 13 elasticity elasticity NN cord-014597-66vd2mdu 2418 14 directs direct VBZ cord-014597-66vd2mdu 2418 15 stem stem NN cord-014597-66vd2mdu 2418 16 cell cell NN cord-014597-66vd2mdu 2418 17 Lineage lineage NN cord-014597-66vd2mdu 2418 18 specification specification NN cord-014597-66vd2mdu 2418 19 Continuous continuous JJ cord-014597-66vd2mdu 2418 20 cider cider NN cord-014597-66vd2mdu 2418 21 fermentation fermentation NN cord-014597-66vd2mdu 2418 22 with with IN cord-014597-66vd2mdu 2418 23 co co JJ cord-014597-66vd2mdu 2418 24 - - JJ cord-014597-66vd2mdu 2418 25 immobilized immobilize VBN cord-014597-66vd2mdu 2418 26 yeast yeast NN cord-014597-66vd2mdu 2418 27 and and CC cord-014597-66vd2mdu 2418 28 Leuconostoc Leuconostoc NNP cord-014597-66vd2mdu 2418 29 oenos oenos NN cord-014597-66vd2mdu 2418 30 cells cell VBZ cord-014597-66vd2mdu 2418 31 Eternity eternity NN cord-014597-66vd2mdu 2418 32 and and CC cord-014597-66vd2mdu 2418 33 functionality functionality NN cord-014597-66vd2mdu 2418 34 -rational -rational JJ cord-014597-66vd2mdu 2418 35 access access NN cord-014597-66vd2mdu 2418 36 to to IN cord-014597-66vd2mdu 2418 37 physiologically physiologically RB cord-014597-66vd2mdu 2418 38 relevant relevant JJ cord-014597-66vd2mdu 2418 39 cell cell NN cord-014597-66vd2mdu 2418 40 lines line NNS cord-014597-66vd2mdu 2418 41 Generation generation NN cord-014597-66vd2mdu 2418 42 and and CC cord-014597-66vd2mdu 2418 43 characterization characterization NN cord-014597-66vd2mdu 2418 44 of of IN cord-014597-66vd2mdu 2418 45 two two CD cord-014597-66vd2mdu 2418 46 immortalized immortalize VBN cord-014597-66vd2mdu 2418 47 human human JJ cord-014597-66vd2mdu 2418 48 osteoblastic osteoblastic JJ cord-014597-66vd2mdu 2418 49 cell cell NN cord-014597-66vd2mdu 2418 50 lines line NNS cord-014597-66vd2mdu 2418 51 useful useful JJ cord-014597-66vd2mdu 2418 52 for for IN cord-014597-66vd2mdu 2418 53 epigenetic epigenetic JJ cord-014597-66vd2mdu 2418 54 studies study NNS cord-014597-66vd2mdu 2418 55 Biocompatibility Biocompatibility NNP cord-014597-66vd2mdu 2418 56 of of IN cord-014597-66vd2mdu 2418 57 NanoShuttleTM NanoShuttleTM NNP cord-014597-66vd2mdu 2418 58 and and CC cord-014597-66vd2mdu 2419 1 the the DT cord-014597-66vd2mdu 2419 2 magnetic magnetic JJ cord-014597-66vd2mdu 2419 3 field field NN cord-014597-66vd2mdu 2419 4 in in IN cord-014597-66vd2mdu 2419 5 magnetic magnetic JJ cord-014597-66vd2mdu 2419 6 3D 3D NNP cord-014597-66vd2mdu 2419 7 bioprinting bioprinting NNP cord-014597-66vd2mdu 2419 8 Publisher Publisher NNP cord-014597-66vd2mdu 2419 9 's 's POS cord-014597-66vd2mdu 2419 10 Note Note NNP cord-014597-66vd2mdu 2419 11 Springer Springer NNP cord-014597-66vd2mdu 2419 12 Nature Nature NNP cord-014597-66vd2mdu 2419 13 remains remain VBZ cord-014597-66vd2mdu 2419 14 neutral neutral JJ cord-014597-66vd2mdu 2419 15 with with IN cord-014597-66vd2mdu 2419 16 regard regard NN cord-014597-66vd2mdu 2419 17 to to IN cord-014597-66vd2mdu 2419 18 jurisdictional jurisdictional JJ cord-014597-66vd2mdu 2419 19 claims claim NNS cord-014597-66vd2mdu 2419 20 in in IN cord-014597-66vd2mdu 2419 21 published publish VBN cord-014597-66vd2mdu 2419 22 maps map NNS cord-014597-66vd2mdu 2419 23 and and CC cord-014597-66vd2mdu 2419 24 institutional institutional JJ cord-014597-66vd2mdu 2419 25 affiliations affiliation NNS cord-014597-66vd2mdu 2420 1 We -PRON- PRP cord-014597-66vd2mdu 2420 2 accept accept VBP cord-014597-66vd2mdu 2420 3 pre pre JJ cord-014597-66vd2mdu 2420 4 - - JJ cord-014597-66vd2mdu 2420 5 submission submission JJ cord-014597-66vd2mdu 2420 6 inquiries inquiry NNS cord-014597-66vd2mdu 2421 1 • • NNP cord-014597-66vd2mdu 2422 1 Our -PRON- PRP$ cord-014597-66vd2mdu 2422 2 selector selector NN cord-014597-66vd2mdu 2422 3 tool tool NN cord-014597-66vd2mdu 2422 4 helps help VBZ cord-014597-66vd2mdu 2422 5 you -PRON- PRP cord-014597-66vd2mdu 2422 6 to to TO cord-014597-66vd2mdu 2422 7 find find VB cord-014597-66vd2mdu 2422 8 the the DT cord-014597-66vd2mdu 2422 9 most most RBS cord-014597-66vd2mdu 2422 10 relevant relevant JJ cord-014597-66vd2mdu 2422 11 journal journal NN cord-014597-66vd2mdu 2423 1 • • NNP cord-014597-66vd2mdu 2424 1 We -PRON- PRP cord-014597-66vd2mdu 2424 2 provide provide VBP cord-014597-66vd2mdu 2424 3 round round IN cord-014597-66vd2mdu 2424 4 the the DT cord-014597-66vd2mdu 2424 5 clock clock NN cord-014597-66vd2mdu 2424 6 customer customer NN cord-014597-66vd2mdu 2424 7 support support NN cord-014597-66vd2mdu 2425 1 • • NNP cord-014597-66vd2mdu 2426 1 Convenient convenient JJ cord-014597-66vd2mdu 2426 2 online online JJ cord-014597-66vd2mdu 2426 3 submission submission NN cord-014597-66vd2mdu 2427 1 • • NNP cord-014597-66vd2mdu 2428 1 Thorough thorough JJ cord-014597-66vd2mdu 2428 2 peer peer NN cord-014597-66vd2mdu 2428 3 review review NN cord-014597-66vd2mdu 2429 1 • • NNP cord-014597-66vd2mdu 2430 1 Inclusion inclusion NN cord-014597-66vd2mdu 2430 2 in in IN cord-014597-66vd2mdu 2430 3 PubMed PubMed NNP cord-014597-66vd2mdu 2430 4 and and CC cord-014597-66vd2mdu 2430 5 all all DT cord-014597-66vd2mdu 2430 6 major major JJ cord-014597-66vd2mdu 2430 7 indexing indexing NN cord-014597-66vd2mdu 2430 8 services service NNS cord-014597-66vd2mdu 2431 1 • • NNP cord-014597-66vd2mdu 2432 1 Maximum maximum JJ cord-014597-66vd2mdu 2432 2 visibility visibility NN cord-014597-66vd2mdu 2432 3 for for IN cord-014597-66vd2mdu 2432 4 your -PRON- PRP$ cord-014597-66vd2mdu 2432 5 research research NN cord-014597-66vd2mdu 2432 6 Submit submit VB cord-014597-66vd2mdu 2432 7 your -PRON- PRP$ cord-014597-66vd2mdu 2432 8 manuscript manuscript NN cord-014597-66vd2mdu 2432 9 at at IN cord-014597-66vd2mdu 2432 10 www www NNP cord-014597-66vd2mdu 2432 11 Submit submit VB cord-014597-66vd2mdu 2432 12 your -PRON- PRP$ cord-014597-66vd2mdu 2432 13 next next JJ cord-014597-66vd2mdu 2432 14 manuscript manuscript NN cord-014597-66vd2mdu 2432 15 to to IN cord-014597-66vd2mdu 2432 16 BioMed BioMed NNP cord-014597-66vd2mdu 2432 17 Central Central NNP cord-014597-66vd2mdu 2432 18 and and CC cord-014597-66vd2mdu 2432 19 we -PRON- PRP cord-014597-66vd2mdu 2432 20 will will MD cord-014597-66vd2mdu 2432 21 help help VB cord-014597-66vd2mdu 2432 22 you -PRON- PRP cord-014597-66vd2mdu 2432 23 at at IN cord-014597-66vd2mdu 2432 24 every every DT cord-014597-66vd2mdu 2432 25 step step NN cord-014597-66vd2mdu 2433 1 Authors author NNS cord-014597-66vd2mdu 2433 2 thankfully thankfully RB cord-014597-66vd2mdu 2433 3 acknowledge acknowledge VBP cord-014597-66vd2mdu 2433 4 the the DT cord-014597-66vd2mdu 2433 5 Biotechnology Biotechnology NNP cord-014597-66vd2mdu 2433 6 and and CC cord-014597-66vd2mdu 2433 7 Biological Biological NNP cord-014597-66vd2mdu 2433 8 Sciences Sciences NNPS cord-014597-66vd2mdu 2433 9 Research Research NNP cord-014597-66vd2mdu 2433 10 Council Council NNP cord-014597-66vd2mdu 2433 11 for for IN cord-014597-66vd2mdu 2433 12 funding fund VBG cord-014597-66vd2mdu 2433 13 this this DT cord-014597-66vd2mdu 2433 14 research research NN cord-014597-66vd2mdu 2433 15 work work NN cord-014597-66vd2mdu 2433 16 . . . cord-014597-66vd2mdu 2434 1 SNS SNS NNP cord-014597-66vd2mdu 2434 2 thanks thank NNS cord-014597-66vd2mdu 2434 3 ESACT ESACT NNP cord-014597-66vd2mdu 2434 4 2017 2017 CD cord-014597-66vd2mdu 2434 5 for for IN cord-014597-66vd2mdu 2434 6 providing provide VBG cord-014597-66vd2mdu 2434 7 her -PRON- PRP cord-014597-66vd2mdu 2434 8 with with IN cord-014597-66vd2mdu 2434 9 the the DT cord-014597-66vd2mdu 2434 10 opportunity opportunity NN cord-014597-66vd2mdu 2434 11 to to TO cord-014597-66vd2mdu 2434 12 present present VB cord-014597-66vd2mdu 2434 13 her -PRON- PRP$ cord-014597-66vd2mdu 2434 14 work work NN cord-014597-66vd2mdu 2434 15 at at IN cord-014597-66vd2mdu 2434 16 the the DT cord-014597-66vd2mdu 2434 17 meeting meeting NN cord-014597-66vd2mdu 2434 18 . . . cord-014597-66vd2mdu 2435 1 We -PRON- PRP cord-014597-66vd2mdu 2435 2 would would MD cord-014597-66vd2mdu 2435 3 like like VB cord-014597-66vd2mdu 2435 4 to to TO cord-014597-66vd2mdu 2435 5 thank thank VB cord-014597-66vd2mdu 2435 6 Moritz Moritz NNP cord-014597-66vd2mdu 2435 7 Frei Frei NNP cord-014597-66vd2mdu 2435 8 for for IN cord-014597-66vd2mdu 2435 9 his -PRON- PRP$ cord-014597-66vd2mdu 2435 10 support support NN cord-014597-66vd2mdu 2435 11 for for IN cord-014597-66vd2mdu 2435 12 the the DT cord-014597-66vd2mdu 2435 13 generation generation NN cord-014597-66vd2mdu 2435 14 of of IN cord-014597-66vd2mdu 2435 15 the the DT cord-014597-66vd2mdu 2435 16 NGS NGS NNP cord-014597-66vd2mdu 2435 17 transcriptomics transcriptomics NNPS cord-014597-66vd2mdu 2435 18 data datum NNS cord-014597-66vd2mdu 2435 19 . . . cord-014597-66vd2mdu 2435 20 _SP cord-014597-66vd2mdu 2436 1 Many many JJ cord-014597-66vd2mdu 2436 2 thanks thank NNS cord-014597-66vd2mdu 2436 3 to to IN cord-014597-66vd2mdu 2436 4 Valentine Valentine NNP cord-014597-66vd2mdu 2436 5 Chevallier Chevallier NNP cord-014597-66vd2mdu 2436 6 for for IN cord-014597-66vd2mdu 2436 7 her -PRON- PRP$ cord-014597-66vd2mdu 2436 8 precious precious JJ cord-014597-66vd2mdu 2436 9 advices advice NNS cord-014597-66vd2mdu 2436 10 , , , cord-014597-66vd2mdu 2436 11 to to IN cord-014597-66vd2mdu 2436 12 Stefanos Stefanos NNP cord-014597-66vd2mdu 2436 13 Grammatikos Grammatikos NNP cord-014597-66vd2mdu 2436 14 for for IN cord-014597-66vd2mdu 2436 15 his -PRON- PRP$ cord-014597-66vd2mdu 2436 16 support support NN cord-014597-66vd2mdu 2436 17 and and CC cord-014597-66vd2mdu 2436 18 to to IN cord-014597-66vd2mdu 2436 19 the the DT cord-014597-66vd2mdu 2436 20 whole whole JJ cord-014597-66vd2mdu 2436 21 Upstream Upstream NNP cord-014597-66vd2mdu 2436 22 Process Process NNP cord-014597-66vd2mdu 2436 23 Sciences Sciences NNPS cord-014597-66vd2mdu 2436 24 team team NN cord-014597-66vd2mdu 2436 25 . . . cord-014597-66vd2mdu 2437 1 We -PRON- PRP cord-014597-66vd2mdu 2437 2 thank thank VBP cord-014597-66vd2mdu 2437 3 David David NNP cord-014597-66vd2mdu 2437 4 Bruehlmann Bruehlmann NNP cord-014597-66vd2mdu 2437 5 and and CC cord-014597-66vd2mdu 2437 6 Thomas Thomas NNP cord-014597-66vd2mdu 2437 7 Vuillemin Vuillemin NNP cord-014597-66vd2mdu 2437 8 from from IN cord-014597-66vd2mdu 2437 9 Merck Merck NNP cord-014597-66vd2mdu 2437 10 ( ( -LRB- cord-014597-66vd2mdu 2437 11 Vevey Vevey NNP cord-014597-66vd2mdu 2437 12 , , , cord-014597-66vd2mdu 2437 13 Switzerland Switzerland NNP cord-014597-66vd2mdu 2437 14 ) ) -RRB- cord-014597-66vd2mdu 2437 15 for for IN cord-014597-66vd2mdu 2437 16 providing provide VBG cord-014597-66vd2mdu 2437 17 the the DT cord-014597-66vd2mdu 2437 18 IgG IgG NNP cord-014597-66vd2mdu 2437 19 glycan glycan NN cord-014597-66vd2mdu 2437 20 variants variant NNS cord-014597-66vd2mdu 2437 21 and and CC cord-014597-66vd2mdu 2437 22 the the DT cord-014597-66vd2mdu 2437 23 2-AB 2-ab CD cord-014597-66vd2mdu 2437 24 - - HYPH cord-014597-66vd2mdu 2437 25 UPLC UPLC NNP cord-014597-66vd2mdu 2437 26 glycan glycan NN cord-014597-66vd2mdu 2437 27 data datum NNS cord-014597-66vd2mdu 2437 28 . . . cord-014597-66vd2mdu 2438 1 Polyplus polyplus NN cord-014597-66vd2mdu 2438 2 - - HYPH cord-014597-66vd2mdu 2438 3 transfection transfection NN cord-014597-66vd2mdu 2438 4 would would MD cord-014597-66vd2mdu 2438 5 like like VB cord-014597-66vd2mdu 2438 6 to to TO cord-014597-66vd2mdu 2438 7 thank thank VB cord-014597-66vd2mdu 2438 8 Généthon Généthon NNP cord-014597-66vd2mdu 2438 9 for for IN cord-014597-66vd2mdu 2438 10 their -PRON- PRP$ cord-014597-66vd2mdu 2438 11 kindly kindly RB cord-014597-66vd2mdu 2438 12 provided provide VBN cord-014597-66vd2mdu 2438 13 data datum NNS cord-014597-66vd2mdu 2438 14 . . . cord-014597-66vd2mdu 2439 1 Acknowledgements acknowledgement NNS cord-014597-66vd2mdu 2439 2 Asmita Asmita NNP cord-014597-66vd2mdu 2439 3 Mukerji Mukerji NNP cord-014597-66vd2mdu 2439 4 , , , cord-014597-66vd2mdu 2439 5 Reetesh Reetesh NNP cord-014597-66vd2mdu 2439 6 PM PM NNP cord-014597-66vd2mdu 2439 7 , , , cord-014597-66vd2mdu 2439 8 Sasi Sasi NNP cord-014597-66vd2mdu 2439 9 Kumar Kumar NNP cord-014597-66vd2mdu 2439 10 K K NNP cord-014597-66vd2mdu 2439 11 , , , cord-014597-66vd2mdu 2439 12 Pilot Pilot NNP cord-014597-66vd2mdu 2439 13 plant plant NN cord-014597-66vd2mdu 2439 14 team team NN cord-014597-66vd2mdu 2439 15 _SP cord-014597-66vd2mdu 2439 16 Acknowledgment Acknowledgment NNP cord-014597-66vd2mdu 2439 17 to to IN cord-014597-66vd2mdu 2439 18 Cedric Cedric NNP cord-014597-66vd2mdu 2439 19 Allier Allier NNP cord-014597-66vd2mdu 2439 20 from from IN cord-014597-66vd2mdu 2439 21 CEA CEA NNP cord-014597-66vd2mdu 2439 22 Leti Leti NNP cord-014597-66vd2mdu 2439 23 , , , cord-014597-66vd2mdu 2439 24 Grenoble Grenoble NNP cord-014597-66vd2mdu 2439 25 , , , cord-014597-66vd2mdu 2439 26 France France NNP cord-014597-66vd2mdu 2439 27 . . . cord-014597-66vd2mdu 2440 1 We -PRON- PRP cord-014597-66vd2mdu 2440 2 would would MD cord-014597-66vd2mdu 2440 3 like like VB cord-014597-66vd2mdu 2440 4 to to TO cord-014597-66vd2mdu 2440 5 thank thank VB cord-014597-66vd2mdu 2440 6 A. A. NNP cord-014597-66vd2mdu 2440 7 Schemel Schemel NNP cord-014597-66vd2mdu 2440 8 and and CC cord-014597-66vd2mdu 2440 9 A. A. NNP cord-014597-66vd2mdu 2440 10 Ehrlich Ehrlich NNP cord-014597-66vd2mdu 2440 11 for for IN cord-014597-66vd2mdu 2440 12 technical technical JJ cord-014597-66vd2mdu 2440 13 assistance assistance NN cord-014597-66vd2mdu 2440 14 . . . cord-014597-66vd2mdu 2441 1 The the DT cord-014597-66vd2mdu 2441 2 authors author NNS cord-014597-66vd2mdu 2441 3 would would MD cord-014597-66vd2mdu 2441 4 like like VB cord-014597-66vd2mdu 2441 5 to to TO cord-014597-66vd2mdu 2441 6 mention mention VB cord-014597-66vd2mdu 2441 7 that that IN cord-014597-66vd2mdu 2441 8 this this DT cord-014597-66vd2mdu 2441 9 research research NN cord-014597-66vd2mdu 2441 10 was be VBD cord-014597-66vd2mdu 2441 11 supported support VBN cord-014597-66vd2mdu 2441 12 by by IN cord-014597-66vd2mdu 2441 13 the the DT cord-014597-66vd2mdu 2441 14 FI FI NNP cord-014597-66vd2mdu 2441 15 - - HYPH cord-014597-66vd2mdu 2441 16 DGR DGR NNP cord-014597-66vd2mdu 2441 17 ( ( -LRB- cord-014597-66vd2mdu 2441 18 2017 2017 CD cord-014597-66vd2mdu 2441 19 ) ) -RRB- cord-014597-66vd2mdu 2441 20 from from IN cord-014597-66vd2mdu 2441 21 Spanish Spanish NNP cord-014597-66vd2mdu 2441 22 Government Government NNP cord-014597-66vd2mdu 2441 23 and and CC cord-014597-66vd2mdu 2441 24 the the DT cord-014597-66vd2mdu 2441 25 project project NN cord-014597-66vd2mdu 2441 26 was be VBD cord-014597-66vd2mdu 2441 27 led lead VBN cord-014597-66vd2mdu 2441 28 by by IN cord-014597-66vd2mdu 2441 29 Prof. Prof. NNP cord-014597-66vd2mdu 2441 30 Jordi Jordi NNP cord-014597-66vd2mdu 2441 31 Joan Joan NNP cord-014597-66vd2mdu 2441 32 Cairó Cairó NNP cord-014597-66vd2mdu 2441 33 Badillo Badillo NNP cord-014597-66vd2mdu 2441 34 . . . cord-014597-66vd2mdu 2442 1 The the DT cord-014597-66vd2mdu 2442 2 authors author NNS cord-014597-66vd2mdu 2442 3 want want VBP cord-014597-66vd2mdu 2442 4 to to TO cord-014597-66vd2mdu 2442 5 thank thank VB cord-014597-66vd2mdu 2442 6 the the DT cord-014597-66vd2mdu 2442 7 Biotech Biotech NNP cord-014597-66vd2mdu 2442 8 Process Process NNP cord-014597-66vd2mdu 2442 9 Sciences Sciences NNPS cord-014597-66vd2mdu 2442 10 team team NN cord-014597-66vd2mdu 2442 11 at at IN cord-014597-66vd2mdu 2442 12 Merck Merck NNP cord-014597-66vd2mdu 2442 13 in in IN cord-014597-66vd2mdu 2442 14 Corsier Corsier NNP cord-014597-66vd2mdu 2442 15 - - HYPH cord-014597-66vd2mdu 2442 16 sur sur FW cord-014597-66vd2mdu 2442 17 - - HYPH cord-014597-66vd2mdu 2442 18 Vevey Vevey NNP cord-014597-66vd2mdu 2442 19 for for IN cord-014597-66vd2mdu 2442 20 their -PRON- PRP$ cord-014597-66vd2mdu 2442 21 support support NN cord-014597-66vd2mdu 2442 22 and and CC cord-014597-66vd2mdu 2442 23 also also RB cord-014597-66vd2mdu 2442 24 the the DT cord-014597-66vd2mdu 2442 25 members member NNS cord-014597-66vd2mdu 2442 26 of of IN cord-014597-66vd2mdu 2442 27 the the DT cord-014597-66vd2mdu 2442 28 Morbidelli Morbidelli NNP cord-014597-66vd2mdu 2442 29 group group NN cord-014597-66vd2mdu 2442 30 at at IN cord-014597-66vd2mdu 2442 31 ETH ETH NNP cord-014597-66vd2mdu 2442 32 Zürich Zürich NNP cord-014597-66vd2mdu 2442 33 for for IN cord-014597-66vd2mdu 2442 34 their -PRON- PRP$ cord-014597-66vd2mdu 2442 35 input input NN cord-014597-66vd2mdu 2442 36 and and CC cord-014597-66vd2mdu 2442 37 collaboration collaboration NN cord-014597-66vd2mdu 2442 38 . . . cord-014597-66vd2mdu 2443 1 Authors author NNS cord-014597-66vd2mdu 2443 2 would would MD cord-014597-66vd2mdu 2443 3 like like VB cord-014597-66vd2mdu 2443 4 to to TO cord-014597-66vd2mdu 2443 5 thank thank VB cord-014597-66vd2mdu 2443 6 Dr. Dr. NNP cord-014597-66vd2mdu 2443 7 Benjamin Benjamin NNP cord-014597-66vd2mdu 2443 8 Youn Youn NNP cord-014597-66vd2mdu 2443 9 in in IN cord-014597-66vd2mdu 2443 10 Manufacturing Manufacturing NNP cord-014597-66vd2mdu 2443 11 Science Science NNP cord-014597-66vd2mdu 2443 12 and and CC cord-014597-66vd2mdu 2443 13 Technology Technology NNP cord-014597-66vd2mdu 2443 14 ( ( -LRB- cord-014597-66vd2mdu 2443 15 MSAT MSAT NNP cord-014597-66vd2mdu 2443 16 ) ) -RRB- cord-014597-66vd2mdu 2443 17 at at IN cord-014597-66vd2mdu 2443 18 BioMarin BioMarin NNP cord-014597-66vd2mdu 2443 19 for for IN cord-014597-66vd2mdu 2443 20 his -PRON- PRP$ cord-014597-66vd2mdu 2443 21 help help NN cord-014597-66vd2mdu 2443 22 on on IN cord-014597-66vd2mdu 2443 23 coding code VBG cord-014597-66vd2mdu 2443 24 the the DT cord-014597-66vd2mdu 2443 25 Excel Excel NNP cord-014597-66vd2mdu 2443 26 Macro Macro NNP cord-014597-66vd2mdu 2443 27 program program NN cord-014597-66vd2mdu 2443 28 for for IN cord-014597-66vd2mdu 2443 29 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 2443 30 , , , cord-014597-66vd2mdu 2443 31 and and CC cord-014597-66vd2mdu 2443 32 Dr. Dr. NNP cord-014597-66vd2mdu 2443 33 Donald Donald NNP cord-014597-66vd2mdu 2443 34 L. L. NNP cord-014597-66vd2mdu 2443 35 Traul Traul NNP cord-014597-66vd2mdu 2443 36 from from IN cord-014597-66vd2mdu 2443 37 TAP TAP NNP cord-014597-66vd2mdu 2443 38 Biosystems Biosystems NNP cord-014597-66vd2mdu 2443 39 ( ( -LRB- cord-014597-66vd2mdu 2443 40 now now RB cord-014597-66vd2mdu 2443 41 part part NN cord-014597-66vd2mdu 2443 42 of of IN cord-014597-66vd2mdu 2443 43 the the DT cord-014597-66vd2mdu 2443 44 Sartorius Sartorius NNP cord-014597-66vd2mdu 2443 45 Stedim Stedim NNP cord-014597-66vd2mdu 2443 46 Biotech Biotech NNP cord-014597-66vd2mdu 2443 47 Group Group NNP cord-014597-66vd2mdu 2443 48 ) ) -RRB- cord-014597-66vd2mdu 2443 49 for for IN cord-014597-66vd2mdu 2443 50 his -PRON- PRP$ cord-014597-66vd2mdu 2443 51 assistance assistance NN cord-014597-66vd2mdu 2443 52 on on IN cord-014597-66vd2mdu 2443 53 AMBR15 AMBR15 NNP cord-014597-66vd2mdu 2443 54 operations operation NNS cord-014597-66vd2mdu 2443 55 . . . cord-014597-66vd2mdu 2444 1 Thanks thank NNS cord-014597-66vd2mdu 2444 2 to to IN cord-014597-66vd2mdu 2444 3 the the DT cord-014597-66vd2mdu 2444 4 bioreactor bioreactor NN cord-014597-66vd2mdu 2444 5 team team NN cord-014597-66vd2mdu 2444 6 of of IN cord-014597-66vd2mdu 2444 7 Dustin Dustin NNP cord-014597-66vd2mdu 2444 8 Davis Davis NNP cord-014597-66vd2mdu 2444 9 , , , cord-014597-66vd2mdu 2444 10 Amer Amer NNP cord-014597-66vd2mdu 2444 11 Al Al NNP cord-014597-66vd2mdu 2444 12 - - HYPH cord-014597-66vd2mdu 2444 13 Lozi Lozi NNP cord-014597-66vd2mdu 2444 14 , , , cord-014597-66vd2mdu 2444 15 and and CC cord-014597-66vd2mdu 2444 16 Jana Jana NNP cord-014597-66vd2mdu 2444 17 Mahadevan Mahadevan NNP cord-014597-66vd2mdu 2444 18 . . . cord-014597-66vd2mdu 2445 1 We -PRON- PRP cord-014597-66vd2mdu 2445 2 _SP cord-014597-66vd2mdu 2445 3 Organic Organic NNP cord-014597-66vd2mdu 2445 4 Vaccines Vaccines NNPS cord-014597-66vd2mdu 2445 5 TM TM NNP cord-014597-66vd2mdu 2445 6 and and CC cord-014597-66vd2mdu 2445 7 the the DT cord-014597-66vd2mdu 2445 8 NIH NIH NNP cord-014597-66vd2mdu 2445 9 , , , cord-014597-66vd2mdu 2445 10 who who WP cord-014597-66vd2mdu 2445 11 kindly kindly RB cord-014597-66vd2mdu 2445 12 provided provide VBD cord-014597-66vd2mdu 2445 13 to to IN cord-014597-66vd2mdu 2445 14 Univercells Univercells NNP cord-014597-66vd2mdu 2445 15 . . . cord-014597-66vd2mdu 2446 1 We -PRON- PRP cord-014597-66vd2mdu 2446 2 thank thank VBP cord-014597-66vd2mdu 2446 3 Polymun Polymun NNP cord-014597-66vd2mdu 2446 4 Scientific Scientific NNP cord-014597-66vd2mdu 2446 5 Immunbiologische Immunbiologische NNP cord-014597-66vd2mdu 2446 6 Forschung Forschung NNP cord-014597-66vd2mdu 2446 7 GmbH GmbH NNP cord-014597-66vd2mdu 2446 8 for for IN cord-014597-66vd2mdu 2446 9 providing provide VBG cord-014597-66vd2mdu 2446 10 the the DT cord-014597-66vd2mdu 2446 11 antibodies antibody NNS cord-014597-66vd2mdu 2446 12 IgM103 IgM103 NNP cord-014597-66vd2mdu 2446 13 , , , cord-014597-66vd2mdu 2446 14 IgM104 IgM104 NNP cord-014597-66vd2mdu 2446 15 and and CC cord-014597-66vd2mdu 2446 16 IgM617 IgM617 NNP cord-014597-66vd2mdu 2446 17 as as IN cord-014597-66vd2mdu 2446 18 a a DT cord-014597-66vd2mdu 2446 19 kind kind JJ cord-014597-66vd2mdu 2446 20 gift gift NN cord-014597-66vd2mdu 2446 21 . . . cord-014597-66vd2mdu 2447 1 This this DT cord-014597-66vd2mdu 2447 2 Allison Allison NNP cord-014597-66vd2mdu 2447 3 Kurz Kurz NNP cord-014597-66vd2mdu 2447 4 and and CC cord-014597-66vd2mdu 2447 5 Gian Gian NNP cord-014597-66vd2mdu 2447 6 Andrea Andrea NNP cord-014597-66vd2mdu 2447 7 Signorell Signorell NNP cord-014597-66vd2mdu 2447 8 , , , cord-014597-66vd2mdu 2447 9 Genedata Genedata NNP cord-014597-66vd2mdu 2447 10 AG AG NNP cord-014597-66vd2mdu 2447 11 , , , cord-014597-66vd2mdu 2447 12 Basel Basel NNP cord-014597-66vd2mdu 2447 13 , , , cord-014597-66vd2mdu 2447 14 Switzerland Switzerland NNP cord-014597-66vd2mdu 2447 15 Allison Allison NNP cord-014597-66vd2mdu 2447 16 Kurz Kurz NNP cord-014597-66vd2mdu 2447 17 , , , cord-014597-66vd2mdu 2447 18 Gian Gian NNP cord-014597-66vd2mdu 2447 19 Andrea Andrea NNP cord-014597-66vd2mdu 2447 20 Signorell Signorell NNP cord-014597-66vd2mdu 2447 21 , , , cord-014597-66vd2mdu 2447 22 Genedata Genedata NNP cord-014597-66vd2mdu 2447 23 , , , cord-014597-66vd2mdu 2447 24 Basel Basel NNP cord-014597-66vd2mdu 2447 25 , , , cord-014597-66vd2mdu 2447 26 Switzerland Switzerland NNP cord-014597-66vd2mdu 2447 27 . . . cord-014597-66vd2mdu 2448 1 Allison Allison NNP cord-014597-66vd2mdu 2448 2 Kurz Kurz NNP cord-014597-66vd2mdu 2448 3 , , , cord-014597-66vd2mdu 2448 4 Gian Gian NNP cord-014597-66vd2mdu 2448 5 Andrea Andrea NNP cord-014597-66vd2mdu 2448 6 Signorell Signorell NNP cord-014597-66vd2mdu 2448 7 , , , cord-014597-66vd2mdu 2448 8 Genedata Genedata NNP cord-014597-66vd2mdu 2448 9 AG AG NNP cord-014597-66vd2mdu 2448 10 High high JJ cord-014597-66vd2mdu 2448 11 glucose glucose NN cord-014597-66vd2mdu 2448 12 concentration concentration NN cord-014597-66vd2mdu 2448 13 and and CC cord-014597-66vd2mdu 2448 14 low low JJ cord-014597-66vd2mdu 2448 15 specific specific JJ cord-014597-66vd2mdu 2448 16 cell cell NN cord-014597-66vd2mdu 2448 17 growth growth NN cord-014597-66vd2mdu 2448 18 rate rate NN cord-014597-66vd2mdu 2448 19 improve improve VBP cord-014597-66vd2mdu 2448 20 specific specific JJ cord-014597-66vd2mdu 2448 21 r r NN cord-014597-66vd2mdu 2448 22 - - HYPH cord-014597-66vd2mdu 2448 23 tPA tpa NN cord-014597-66vd2mdu 2448 24 productivity productivity NN cord-014597-66vd2mdu 2448 25 in in IN cord-014597-66vd2mdu 2448 26 chemostat chemostat NN cord-014597-66vd2mdu 2448 27 culture culture NN cord-014597-66vd2mdu 2448 28 of of IN cord-014597-66vd2mdu 2448 29 CHO CHO NNP cord-014597-66vd2mdu 2448 30 Acknowledgements Acknowledgements NNP cord-014597-66vd2mdu 2448 31 R. R. NNP cord-014597-66vd2mdu 2448 32 Boraston Boraston NNP cord-014597-66vd2mdu 2448 33 for for IN cord-014597-66vd2mdu 2448 34 photographs photograph NNS cord-014597-66vd2mdu 2448 35 in in IN cord-014597-66vd2mdu 2448 36 Fig Fig NNP cord-014597-66vd2mdu 2448 37 . . . cord-014597-66vd2mdu 2449 1 1 1 LS cord-014597-66vd2mdu 2449 2 . . . cord-014597-66vd2mdu 2450 1 We -PRON- PRP cord-014597-66vd2mdu 2450 2 acknowledge acknowledge VBP cord-014597-66vd2mdu 2450 3 Atum Atum NNP cord-014597-66vd2mdu 2450 4 for for IN cord-014597-66vd2mdu 2450 5 their -PRON- PRP$ cord-014597-66vd2mdu 2450 6 contributions contribution NNS cord-014597-66vd2mdu 2450 7 to to IN cord-014597-66vd2mdu 2450 8 vector vector NN cord-014597-66vd2mdu 2450 9 design design NN cord-014597-66vd2mdu 2450 10 and and CC cord-014597-66vd2mdu 2450 11 construction construction NN cord-014597-66vd2mdu 2450 12 . . . cord-014597-66vd2mdu 2451 1 Austrian Austrian NNP cord-014597-66vd2mdu 2451 2 BMWFW BMWFW NNP cord-014597-66vd2mdu 2451 3 , , , cord-014597-66vd2mdu 2451 4 BMVIT BMVIT NNP cord-014597-66vd2mdu 2451 5 , , , cord-014597-66vd2mdu 2451 6 SFG SFG NNP cord-014597-66vd2mdu 2451 7 , , , cord-014597-66vd2mdu 2451 8 Standortagentur Standortagentur NNP cord-014597-66vd2mdu 2451 9 Tirol Tirol NNP cord-014597-66vd2mdu 2451 10 , , , cord-014597-66vd2mdu 2451 11 Government Government NNP cord-014597-66vd2mdu 2451 12 of of IN cord-014597-66vd2mdu 2451 13 Lower Lower NNP cord-014597-66vd2mdu 2451 14 Austria Austria NNP cord-014597-66vd2mdu 2451 15 and and CC cord-014597-66vd2mdu 2451 16 Business Business NNP cord-014597-66vd2mdu 2451 17 Agency Agency NNP cord-014597-66vd2mdu 2451 18 Vienna Vienna NNP cord-014597-66vd2mdu 2451 19 through through IN cord-014597-66vd2mdu 2451 20 the the DT cord-014597-66vd2mdu 2451 21 Austrian austrian JJ cord-014597-66vd2mdu 2451 22 FFG FFG NNP cord-014597-66vd2mdu 2451 23 - - HYPH cord-014597-66vd2mdu 2451 24 COMET COMET NNP cord-014597-66vd2mdu 2451 25 - - HYPH cord-014597-66vd2mdu 2451 26 K2 K2 NNP cord-014597-66vd2mdu 2451 27 . . . cord-014597-66vd2mdu 2452 1 This this DT cord-014597-66vd2mdu 2452 2 research research NN cord-014597-66vd2mdu 2452 3 is be VBZ cord-014597-66vd2mdu 2452 4 supported support VBN cord-014597-66vd2mdu 2452 5 by by IN cord-014597-66vd2mdu 2452 6 SFI SFI NNP cord-014597-66vd2mdu 2452 7 Grant Grant NNP cord-014597-66vd2mdu 2452 8 13 13 CD cord-014597-66vd2mdu 2453 1 /IA/1841 /IA/1841 NFP cord-014597-66vd2mdu 2453 2 . . . cord-014597-66vd2mdu 2453 3 _SP cord-014597-66vd2mdu 2454 1 Financial financial JJ cord-014597-66vd2mdu 2454 2 support support NN cord-014597-66vd2mdu 2454 3 of of IN cord-014597-66vd2mdu 2454 4 the the DT cord-014597-66vd2mdu 2454 5 Austrian Austrian NNP cord-014597-66vd2mdu 2454 6 Science Science NNP cord-014597-66vd2mdu 2454 7 Fund Fund NNP cord-014597-66vd2mdu 2454 8 ( ( -LRB- cord-014597-66vd2mdu 2454 9 FWF FWF NNP cord-014597-66vd2mdu 2454 10 ; ; , cord-014597-66vd2mdu 2454 11 grant grant NN cord-014597-66vd2mdu 2454 12 number number NN cord-014597-66vd2mdu 2454 13 P p NN cord-014597-66vd2mdu 2454 14 25056 25056 CD cord-014597-66vd2mdu 2454 15 ) ) -RRB- cord-014597-66vd2mdu 2454 16 is be VBZ cord-014597-66vd2mdu 2454 17 gratefully gratefully RB cord-014597-66vd2mdu 2454 18 acknowledged acknowledge VBN cord-014597-66vd2mdu 2454 19 . . . cord-014597-66vd2mdu 2455 1 We -PRON- PRP cord-014597-66vd2mdu 2455 2 would would MD cord-014597-66vd2mdu 2455 3 like like VB cord-014597-66vd2mdu 2455 4 to to TO cord-014597-66vd2mdu 2455 5 thank thank VB cord-014597-66vd2mdu 2455 6 the the DT cord-014597-66vd2mdu 2455 7 Australian Australian NNP cord-014597-66vd2mdu 2455 8 Institute Institute NNP cord-014597-66vd2mdu 2455 9 for for IN cord-014597-66vd2mdu 2455 10 Bioengineering Bioengineering NNP cord-014597-66vd2mdu 2455 11 and and CC cord-014597-66vd2mdu 2455 12 Nanotechnology Nanotechnology NNP cord-014597-66vd2mdu 2455 13 , , , cord-014597-66vd2mdu 2455 14 University University NNP cord-014597-66vd2mdu 2455 15 of of IN cord-014597-66vd2mdu 2455 16 Queensland Queensland NNP cord-014597-66vd2mdu 2455 17 - - HYPH cord-014597-66vd2mdu 2455 18 Brisbane Brisbane NNP cord-014597-66vd2mdu 2455 19 , , , cord-014597-66vd2mdu 2455 20 Australia Australia NNP cord-014597-66vd2mdu 2455 21 ( ( -LRB- cord-014597-66vd2mdu 2455 22 AIBN AIBN NNP cord-014597-66vd2mdu 2455 23 ) ) -RRB- cord-014597-66vd2mdu 2455 24 for for IN cord-014597-66vd2mdu 2455 25 providing provide VBG cord-014597-66vd2mdu 2455 26 the the DT cord-014597-66vd2mdu 2455 27 CHO CHO NNP cord-014597-66vd2mdu 2455 28 clones clone NNS cord-014597-66vd2mdu 2455 29 . . . cord-014597-66vd2mdu 2456 1 This this DT cord-014597-66vd2mdu 2456 2 research research NN cord-014597-66vd2mdu 2456 3 is be VBZ cord-014597-66vd2mdu 2456 4 partially partially RB cord-014597-66vd2mdu 2456 5 supported support VBN cord-014597-66vd2mdu 2456 6 by by IN cord-014597-66vd2mdu 2456 7 the the DT cord-014597-66vd2mdu 2456 8 developing develop VBG cord-014597-66vd2mdu 2456 9 key key JJ cord-014597-66vd2mdu 2456 10 technologies technology NNS cord-014597-66vd2mdu 2456 11 for for IN cord-014597-66vd2mdu 2456 12 discovering discover VBG cord-014597-66vd2mdu 2456 13 and and CC cord-014597-66vd2mdu 2456 14 manufacturing manufacturing NN cord-014597-66vd2mdu 2456 15 pharmaceuticals pharmaceutical NNS cord-014597-66vd2mdu 2456 16 used use VBN cord-014597-66vd2mdu 2456 17 for for IN cord-014597-66vd2mdu 2456 18 next next JJ cord-014597-66vd2mdu 2456 19 - - HYPH cord-014597-66vd2mdu 2456 20 generation generation NN cord-014597-66vd2mdu 2456 21 treatments treatment NNS cord-014597-66vd2mdu 2456 22 and and CC cord-014597-66vd2mdu 2456 23 diagnoses diagnosis NNS cord-014597-66vd2mdu 2456 24 both both DT cord-014597-66vd2mdu 2456 25 from from IN cord-014597-66vd2mdu 2456 26 METI METI NNP cord-014597-66vd2mdu 2456 27 and and CC cord-014597-66vd2mdu 2456 28 AMED AMED NNP cord-014597-66vd2mdu 2456 29 , , , cord-014597-66vd2mdu 2456 30 Japan Japan NNP cord-014597-66vd2mdu 2456 31 . . . cord-014597-66vd2mdu 2456 32 _SP cord-014597-66vd2mdu 2457 1 This this DT cord-014597-66vd2mdu 2457 2 work work NN cord-014597-66vd2mdu 2457 3 was be VBD cord-014597-66vd2mdu 2457 4 supported support VBN cord-014597-66vd2mdu 2457 5 in in IN cord-014597-66vd2mdu 2457 6 part part NN cord-014597-66vd2mdu 2457 7 by by IN cord-014597-66vd2mdu 2457 8 grants grant NNS cord-014597-66vd2mdu 2457 9 for for IN cord-014597-66vd2mdu 2457 10 developing develop VBG cord-014597-66vd2mdu 2457 11 key key JJ cord-014597-66vd2mdu 2457 12 technologies technology NNS cord-014597-66vd2mdu 2457 13 for for IN cord-014597-66vd2mdu 2457 14 discovering discover VBG cord-014597-66vd2mdu 2457 15 and and CC cord-014597-66vd2mdu 2457 16 manufacturing manufacturing NN cord-014597-66vd2mdu 2457 17 pharmaceuticals pharmaceutical NNS cord-014597-66vd2mdu 2457 18 used use VBN cord-014597-66vd2mdu 2457 19 for for IN cord-014597-66vd2mdu 2457 20 next next JJ cord-014597-66vd2mdu 2457 21 - - HYPH cord-014597-66vd2mdu 2457 22 generation generation NN cord-014597-66vd2mdu 2457 23 treatment treatment NN cord-014597-66vd2mdu 2457 24 and and CC cord-014597-66vd2mdu 2457 25 diagnoses diagnosis NNS cord-014597-66vd2mdu 2457 26 , , , cord-014597-66vd2mdu 2457 27 both both CC cord-014597-66vd2mdu 2457 28 from from IN cord-014597-66vd2mdu 2457 29 the the DT cord-014597-66vd2mdu 2457 30 Ministry Ministry NNP cord-014597-66vd2mdu 2457 31 of of IN cord-014597-66vd2mdu 2457 32 Economy Economy NNP cord-014597-66vd2mdu 2457 33 , , , cord-014597-66vd2mdu 2457 34 Trade Trade NNP cord-014597-66vd2mdu 2457 35 and and CC cord-014597-66vd2mdu 2457 36 Industry Industry NNP cord-014597-66vd2mdu 2457 37 ( ( -LRB- cord-014597-66vd2mdu 2457 38 METI METI NNP cord-014597-66vd2mdu 2457 39 ) ) -RRB- cord-014597-66vd2mdu 2457 40 , , , cord-014597-66vd2mdu 2457 41 Japan Japan NNP cord-014597-66vd2mdu 2457 42 and and CC cord-014597-66vd2mdu 2457 43 from from IN cord-014597-66vd2mdu 2457 44 the the DT cord-014597-66vd2mdu 2457 45 Japan Japan NNP cord-014597-66vd2mdu 2457 46 Agency Agency NNP cord-014597-66vd2mdu 2457 47 for for IN cord-014597-66vd2mdu 2457 48 Medical Medical NNP cord-014597-66vd2mdu 2457 49 Research Research NNP cord-014597-66vd2mdu 2457 50 and and CC cord-014597-66vd2mdu 2457 51 Developments Developments NNPS cord-014597-66vd2mdu 2457 52 ( ( -LRB- cord-014597-66vd2mdu 2457 53 AMED AMED NNP cord-014597-66vd2mdu 2457 54 ) ) -RRB- cord-014597-66vd2mdu 2457 55 . . . cord-014597-66vd2mdu 2458 1 Many many JJ cord-014597-66vd2mdu 2458 2 thanks thank NNS cord-014597-66vd2mdu 2458 3 Stefanos Stefanos NNP cord-014597-66vd2mdu 2458 4 Grammatikos Grammatikos NNP cord-014597-66vd2mdu 2458 5 for for IN cord-014597-66vd2mdu 2458 6 his -PRON- PRP$ cord-014597-66vd2mdu 2458 7 support support NN cord-014597-66vd2mdu 2458 8 and and CC cord-014597-66vd2mdu 2458 9 to to IN cord-014597-66vd2mdu 2458 10 the the DT cord-014597-66vd2mdu 2458 11 whole whole JJ cord-014597-66vd2mdu 2458 12 Upstream Upstream NNP cord-014597-66vd2mdu 2458 13 Process Process NNP cord-014597-66vd2mdu 2458 14 Sciences Sciences NNPS cord-014597-66vd2mdu 2458 15 team team NN cord-014597-66vd2mdu 2458 16 . . . cord-014597-66vd2mdu 2459 1 The the DT cord-014597-66vd2mdu 2459 2 authors author NNS cord-014597-66vd2mdu 2459 3 thank thank VBP cord-014597-66vd2mdu 2459 4 the the DT cord-014597-66vd2mdu 2459 5 Hessen Hessen NNP cord-014597-66vd2mdu 2459 6 State State NNP cord-014597-66vd2mdu 2459 7 Ministry Ministry NNP cord-014597-66vd2mdu 2459 8 of of IN cord-014597-66vd2mdu 2459 9 Higher Higher NNP cord-014597-66vd2mdu 2459 10 Education Education NNP cord-014597-66vd2mdu 2459 11 , , , cord-014597-66vd2mdu 2459 12 Research Research NNP cord-014597-66vd2mdu 2459 13 and and CC cord-014597-66vd2mdu 2459 14 the the DT cord-014597-66vd2mdu 2459 15 Arts art NNS cord-014597-66vd2mdu 2459 16 within within IN cord-014597-66vd2mdu 2459 17 the the DT cord-014597-66vd2mdu 2459 18 Hessen Hessen NNP cord-014597-66vd2mdu 2459 19 initiative initiative NN cord-014597-66vd2mdu 2459 20 for for IN cord-014597-66vd2mdu 2459 21 scientific scientific JJ cord-014597-66vd2mdu 2459 22 and and CC cord-014597-66vd2mdu 2459 23 economic economic JJ cord-014597-66vd2mdu 2459 24 excellence excellence NN cord-014597-66vd2mdu 2459 25 ( ( -LRB- cord-014597-66vd2mdu 2459 26 LOEWE LOEWE NNP cord-014597-66vd2mdu 2459 27 Program Program NNP cord-014597-66vd2mdu 2459 28 ) ) -RRB- cord-014597-66vd2mdu 2459 29 for for IN cord-014597-66vd2mdu 2459 30 the the DT cord-014597-66vd2mdu 2459 31 financial financial JJ cord-014597-66vd2mdu 2459 32 support support NN cord-014597-66vd2mdu 2459 33 . . . cord-014597-66vd2mdu 2459 34 _SP cord-014597-66vd2mdu 2460 1 The the DT cord-014597-66vd2mdu 2460 2 authors author NNS cord-014597-66vd2mdu 2460 3 thank thank VBP cord-014597-66vd2mdu 2460 4 Xell Xell NNP cord-014597-66vd2mdu 2460 5 AG AG NNP cord-014597-66vd2mdu 2460 6 , , , cord-014597-66vd2mdu 2460 7 Bielefeld Bielefeld NNP cord-014597-66vd2mdu 2460 8 , , , cord-014597-66vd2mdu 2460 9 for for IN cord-014597-66vd2mdu 2460 10 providing provide VBG cord-014597-66vd2mdu 2460 11 HEK HEK NNP cord-014597-66vd2mdu 2460 12 serum serum NN cord-014597-66vd2mdu 2460 13 - - HYPH cord-014597-66vd2mdu 2460 14 free free JJ cord-014597-66vd2mdu 2460 15 media medium NNS cord-014597-66vd2mdu 2460 16 ( ( -LRB- cord-014597-66vd2mdu 2460 17 HEK HEK NNP cord-014597-66vd2mdu 2460 18 GM GM NNP cord-014597-66vd2mdu 2460 19 and and CC cord-014597-66vd2mdu 2460 20 HEK HEK NNP cord-014597-66vd2mdu 2460 21 TF TF NNP cord-014597-66vd2mdu 2460 22 ) ) -RRB- cord-014597-66vd2mdu 2460 23 and and CC cord-014597-66vd2mdu 2460 24 for for IN cord-014597-66vd2mdu 2460 25 fruitful fruitful JJ cord-014597-66vd2mdu 2460 26 discussions discussion NNS cord-014597-66vd2mdu 2460 27 . . . cord-014597-66vd2mdu 2461 1 The the DT cord-014597-66vd2mdu 2461 2 authors author NNS cord-014597-66vd2mdu 2461 3 would would MD cord-014597-66vd2mdu 2461 4 like like VB cord-014597-66vd2mdu 2461 5 to to TO cord-014597-66vd2mdu 2461 6 thank thank VB cord-014597-66vd2mdu 2461 7 Dana Dana NNP cord-014597-66vd2mdu 2461 8 Wenzel Wenzel NNP cord-014597-66vd2mdu 2461 9 for for IN cord-014597-66vd2mdu 2461 10 CHO CHO NNP cord-014597-66vd2mdu 2461 11 lysate lysate NN cord-014597-66vd2mdu 2461 12 preparation preparation NN cord-014597-66vd2mdu 2461 13 ( ( -LRB- cord-014597-66vd2mdu 2461 14 Fraunhofer Fraunhofer NNP cord-014597-66vd2mdu 2461 15 IZI IZI NNP cord-014597-66vd2mdu 2461 16 , , , cord-014597-66vd2mdu 2461 17 Potsdam Potsdam NNP cord-014597-66vd2mdu 2461 18 - - HYPH cord-014597-66vd2mdu 2461 19 Golm Golm NNP cord-014597-66vd2mdu 2461 20 , , , cord-014597-66vd2mdu 2461 21 Germany Germany NNP cord-014597-66vd2mdu 2461 22 ) ) -RRB- cord-014597-66vd2mdu 2461 23 . . . cord-014597-66vd2mdu 2462 1 This this DT cord-014597-66vd2mdu 2462 2 work work NN cord-014597-66vd2mdu 2462 3 is be VBZ cord-014597-66vd2mdu 2462 4 supported support VBN cord-014597-66vd2mdu 2462 5 by by IN cord-014597-66vd2mdu 2462 6 the the DT cord-014597-66vd2mdu 2462 7 European European NNP cord-014597-66vd2mdu 2462 8 Regional Regional NNP cord-014597-66vd2mdu 2462 9 Development Development NNP cord-014597-66vd2mdu 2462 10 Fund Fund NNP cord-014597-66vd2mdu 2462 11 ( ( -LRB- cord-014597-66vd2mdu 2462 12 EFRE EFRE NNP cord-014597-66vd2mdu 2462 13 ) ) -RRB- cord-014597-66vd2mdu 2462 14 and and CC cord-014597-66vd2mdu 2462 15 the the DT cord-014597-66vd2mdu 2462 16 German German NNP cord-014597-66vd2mdu 2462 17 Ministry Ministry NNP cord-014597-66vd2mdu 2462 18 of of IN cord-014597-66vd2mdu 2462 19 Education Education NNP cord-014597-66vd2mdu 2462 20 and and CC cord-014597-66vd2mdu 2462 21 Research Research NNP cord-014597-66vd2mdu 2462 22 ( ( -LRB- cord-014597-66vd2mdu 2462 23 BMBF BMBF NNP cord-014597-66vd2mdu 2462 24 , , , cord-014597-66vd2mdu 2462 25 No no NN cord-014597-66vd2mdu 2462 26 . . NN cord-014597-66vd2mdu 2462 27 031B0078A 031b0078a CD cord-014597-66vd2mdu 2462 28 ) ) -RRB- cord-014597-66vd2mdu 2462 29 . . . cord-014597-66vd2mdu 2463 1 The the DT cord-014597-66vd2mdu 2463 2 authors author NNS cord-014597-66vd2mdu 2463 3 acknowledge acknowledge VBP cord-014597-66vd2mdu 2463 4 São São NNP cord-014597-66vd2mdu 2463 5 Paulo Paulo NNP cord-014597-66vd2mdu 2463 6 Research Research NNP cord-014597-66vd2mdu 2463 7 Foundation Foundation NNP cord-014597-66vd2mdu 2463 8 -FAPESP -FAPESP . cord-014597-66vd2mdu 2464 1 ( ( -LRB- cord-014597-66vd2mdu 2464 2 2015/ 2015/ CD cord-014597-66vd2mdu 2464 3 19017 19017 CD cord-014597-66vd2mdu 2464 4 - - SYM cord-014597-66vd2mdu 2464 5 6 6 CD cord-014597-66vd2mdu 2464 6 ) ) -RRB- cord-014597-66vd2mdu 2464 7 , , , cord-014597-66vd2mdu 2464 8 Centro Centro NNP cord-014597-66vd2mdu 2464 9 de de NNP cord-014597-66vd2mdu 2464 10 Pesquisa Pesquisa NNP cord-014597-66vd2mdu 2464 11 , , , cord-014597-66vd2mdu 2464 12 Inovação Inovação NNP cord-014597-66vd2mdu 2464 13 e e NN cord-014597-66vd2mdu 2464 14 Difusão Difusão NNP cord-014597-66vd2mdu 2464 15 ( ( -LRB- cord-014597-66vd2mdu 2464 16 CEPID CEPID NNP cord-014597-66vd2mdu 2464 17 ) ) -RRB- cord-014597-66vd2mdu 2464 18 , , , cord-014597-66vd2mdu 2464 19 and and CC cord-014597-66vd2mdu 2464 20 National National NNP cord-014597-66vd2mdu 2464 21 Institute Institute NNP cord-014597-66vd2mdu 2464 22 of of IN cord-014597-66vd2mdu 2464 23 Science Science NNP cord-014597-66vd2mdu 2464 24 and and CC cord-014597-66vd2mdu 2464 25 Technology Technology NNP cord-014597-66vd2mdu 2464 26 in in IN cord-014597-66vd2mdu 2464 27 Stem Stem NNP cord-014597-66vd2mdu 2464 28 Cell Cell NNP cord-014597-66vd2mdu 2464 29 and and CC cord-014597-66vd2mdu 2464 30 Cell Cell NNP cord-014597-66vd2mdu 2464 31 Therapy Therapy NNP cord-014597-66vd2mdu 2464 32 -INCTC -INCTC . cord-014597-66vd2mdu 2464 33 for for IN cord-014597-66vd2mdu 2464 34 financial financial JJ cord-014597-66vd2mdu 2464 35 support support NN cord-014597-66vd2mdu 2464 36 . . . cord-014597-66vd2mdu 2465 1 This this DT cord-014597-66vd2mdu 2465 2 work work NN cord-014597-66vd2mdu 2465 3 was be VBD cord-014597-66vd2mdu 2465 4 supported support VBN cord-014597-66vd2mdu 2465 5 by by IN cord-014597-66vd2mdu 2465 6 grants grant NNS cord-014597-66vd2mdu 2465 7 from from IN cord-014597-66vd2mdu 2465 8 the the DT cord-014597-66vd2mdu 2465 9 Niedersächsisches Niedersächsisches NNP cord-014597-66vd2mdu 2465 10 Ministerium Ministerium NNP cord-014597-66vd2mdu 2465 11 für für IN cord-014597-66vd2mdu 2465 12 Wissenschaft Wissenschaft NNP cord-014597-66vd2mdu 2466 1 und und IN cord-014597-66vd2mdu 2466 2 Kultur Kultur NNP cord-014597-66vd2mdu 2466 3 ( ( -LRB- cord-014597-66vd2mdu 2466 4 80029155 80029155 CD cord-014597-66vd2mdu 2466 5 ) ) -RRB- cord-014597-66vd2mdu 2466 6 and and CC cord-014597-66vd2mdu 2466 7 the the DT cord-014597-66vd2mdu 2466 8 German German NNP cord-014597-66vd2mdu 2466 9 Ministry Ministry NNP cord-014597-66vd2mdu 2466 10 for for IN cord-014597-66vd2mdu 2466 11 Economic Economic NNP cord-014597-66vd2mdu 2466 12 Affairs Affairs NNPS cord-014597-66vd2mdu 2466 13 and and CC cord-014597-66vd2mdu 2466 14 Energy Energy NNP cord-014597-66vd2mdu 2466 15 ( ( -LRB- cord-014597-66vd2mdu 2466 16 IGF IGF NNP cord-014597-66vd2mdu 2466 17 16153 16153 CD cord-014597-66vd2mdu 2466 18 N n CD cord-014597-66vd2mdu 2466 19 ) ) -RRB- cord-014597-66vd2mdu 2466 20 . . . cord-014597-66vd2mdu 2467 1 The the DT cord-014597-66vd2mdu 2467 2 infrastructure infrastructure NN cord-014597-66vd2mdu 2467 3 which which WDT cord-014597-66vd2mdu 2467 4 was be VBD cord-014597-66vd2mdu 2467 5 modularly modularly RB cord-014597-66vd2mdu 2467 6 built build VBN cord-014597-66vd2mdu 2467 7 up up RP cord-014597-66vd2mdu 2467 8 , , , cord-014597-66vd2mdu 2467 9 consists consist VBZ cord-014597-66vd2mdu 2467 10 of of IN cord-014597-66vd2mdu 2467 11 automated automate VBN cord-014597-66vd2mdu 2467 12 liquid liquid NN cord-014597-66vd2mdu 2467 13 handling handling NN cord-014597-66vd2mdu 2467 14 robots robot NNS cord-014597-66vd2mdu 2467 15 , , , cord-014597-66vd2mdu 2467 16 plate plate NN cord-014597-66vd2mdu 2467 17 and and CC cord-014597-66vd2mdu 2467 18 tube tube NN cord-014597-66vd2mdu 2467 19 handling handle VBG cord-014597-66vd2mdu 2467 20 robots robot NNS cord-014597-66vd2mdu 2467 21 as as RB cord-014597-66vd2mdu 2467 22 well well RB cord-014597-66vd2mdu 2467 23 as as IN cord-014597-66vd2mdu 2467 24 incubators incubator NNS cord-014597-66vd2mdu 2467 25 , , , cord-014597-66vd2mdu 2467 26 refrigerator refrigerator NN cord-014597-66vd2mdu 2467 27 and and CC cord-014597-66vd2mdu 2467 28 analysis analysis NN cord-014597-66vd2mdu 2467 29 systems system NNS cord-014597-66vd2mdu 2467 30 as as IN cord-014597-66vd2mdu 2467 31 for for IN cord-014597-66vd2mdu 2467 32 example example NN cord-014597-66vd2mdu 2467 33 an an DT cord-014597-66vd2mdu 2467 34 imaging imaging NN cord-014597-66vd2mdu 2467 35 system system NN cord-014597-66vd2mdu 2467 36 . . . cord-014597-66vd2mdu 2468 1 The the DT cord-014597-66vd2mdu 2468 2 aim aim NN cord-014597-66vd2mdu 2468 3 is be VBZ cord-014597-66vd2mdu 2468 4 to to TO cord-014597-66vd2mdu 2468 5 address address VB cord-014597-66vd2mdu 2468 6 the the DT cord-014597-66vd2mdu 2468 7 need need NN cord-014597-66vd2mdu 2468 8 on on IN cord-014597-66vd2mdu 2468 9 reproducibility reproducibility NN cord-014597-66vd2mdu 2468 10 and and CC cord-014597-66vd2mdu 2468 11 reliability reliability NN cord-014597-66vd2mdu 2468 12 of of IN cord-014597-66vd2mdu 2468 13 results result NNS cord-014597-66vd2mdu 2468 14 and and CC cord-014597-66vd2mdu 2468 15 to to TO cord-014597-66vd2mdu 2468 16 offer offer VB cord-014597-66vd2mdu 2468 17 access access NN cord-014597-66vd2mdu 2468 18 to to IN cord-014597-66vd2mdu 2468 19 a a DT cord-014597-66vd2mdu 2468 20 maximal maximal RB cord-014597-66vd2mdu 2468 21 controlled control VBN cord-014597-66vd2mdu 2468 22 and and CC cord-014597-66vd2mdu 2468 23 automated automate VBN cord-014597-66vd2mdu 2468 24 environment environment NN cord-014597-66vd2mdu 2468 25 . . . cord-014597-66vd2mdu 2469 1 With with IN cord-014597-66vd2mdu 2469 2 the the DT cord-014597-66vd2mdu 2469 3 help help NN cord-014597-66vd2mdu 2469 4 of of IN cord-014597-66vd2mdu 2469 5 a a DT cord-014597-66vd2mdu 2469 6 web web NN cord-014597-66vd2mdu 2469 7 - - HYPH cord-014597-66vd2mdu 2469 8 based base VBN cord-014597-66vd2mdu 2469 9 configurator configurator NN cord-014597-66vd2mdu 2469 10 assay assay NN cord-014597-66vd2mdu 2469 11 selection selection NN cord-014597-66vd2mdu 2469 12 as as RB cord-014597-66vd2mdu 2469 13 well well RB cord-014597-66vd2mdu 2469 14 as as IN cord-014597-66vd2mdu 2469 15 parameterization parameterization NN cord-014597-66vd2mdu 2469 16 of of IN cord-014597-66vd2mdu 2469 17 the the DT cord-014597-66vd2mdu 2469 18 assays assay NNS cord-014597-66vd2mdu 2469 19 can can MD cord-014597-66vd2mdu 2469 20 be be VB cord-014597-66vd2mdu 2469 21 done do VBN cord-014597-66vd2mdu 2469 22 in in IN cord-014597-66vd2mdu 2469 23 an an DT cord-014597-66vd2mdu 2469 24 easy easy JJ cord-014597-66vd2mdu 2469 25 way way NN cord-014597-66vd2mdu 2469 26 . . . cord-014597-66vd2mdu 2470 1 After after IN cord-014597-66vd2mdu 2470 2 the the DT cord-014597-66vd2mdu 2470 3 order order NN cord-014597-66vd2mdu 2470 4 process process NN cord-014597-66vd2mdu 2470 5 , , , cord-014597-66vd2mdu 2470 6 test test NN cord-014597-66vd2mdu 2470 7 items item NNS cord-014597-66vd2mdu 2470 8 can can MD cord-014597-66vd2mdu 2470 9 be be VB cord-014597-66vd2mdu 2470 10 shipped ship VBN cord-014597-66vd2mdu 2470 11 to to IN cord-014597-66vd2mdu 2470 12 the the DT cord-014597-66vd2mdu 2470 13 lab lab NN cord-014597-66vd2mdu 2470 14 . . . cord-014597-66vd2mdu 2471 1 Assays assay NNS cord-014597-66vd2mdu 2471 2 will will MD cord-014597-66vd2mdu 2471 3 be be VB cord-014597-66vd2mdu 2471 4 executed execute VBN cord-014597-66vd2mdu 2471 5 on on IN cord-014597-66vd2mdu 2471 6 the the DT cord-014597-66vd2mdu 2471 7 fully fully RB cord-014597-66vd2mdu 2471 8 automated automate VBN cord-014597-66vd2mdu 2471 9 platform platform NN cord-014597-66vd2mdu 2471 10 . . . cord-014597-66vd2mdu 2472 1 By by IN cord-014597-66vd2mdu 2472 2 capturing capture VBG cord-014597-66vd2mdu 2472 3 in in IN cord-014597-66vd2mdu 2472 4 process process NN cord-014597-66vd2mdu 2472 5 data datum NNS cord-014597-66vd2mdu 2472 6 as as RB cord-014597-66vd2mdu 2472 7 well well RB cord-014597-66vd2mdu 2472 8 as as IN cord-014597-66vd2mdu 2472 9 environmental environmental JJ cord-014597-66vd2mdu 2472 10 conditions condition NNS cord-014597-66vd2mdu 2472 11 , , , cord-014597-66vd2mdu 2472 12 a a DT cord-014597-66vd2mdu 2472 13 real real JJ cord-014597-66vd2mdu 2472 14 complete complete JJ cord-014597-66vd2mdu 2472 15 data data NN cord-014597-66vd2mdu 2472 16 set set NN cord-014597-66vd2mdu 2472 17 is be VBZ cord-014597-66vd2mdu 2472 18 leading lead VBG cord-014597-66vd2mdu 2472 19 to to IN cord-014597-66vd2mdu 2472 20 comprehensively comprehensively RB cord-014597-66vd2mdu 2472 21 results result NNS cord-014597-66vd2mdu 2472 22 . . . cord-014597-66vd2mdu 2473 1 As as RB cord-014597-66vd2mdu 2473 2 soon soon RB cord-014597-66vd2mdu 2473 3 as as IN cord-014597-66vd2mdu 2473 4 results result NNS cord-014597-66vd2mdu 2473 5 are be VBP cord-014597-66vd2mdu 2473 6 available available JJ cord-014597-66vd2mdu 2473 7 during during IN cord-014597-66vd2mdu 2473 8 the the DT cord-014597-66vd2mdu 2473 9 process process NN cord-014597-66vd2mdu 2473 10 , , , cord-014597-66vd2mdu 2473 11 the the DT cord-014597-66vd2mdu 2473 12 view view NN cord-014597-66vd2mdu 2473 13 and and CC cord-014597-66vd2mdu 2473 14 analysing analysing NN cord-014597-66vd2mdu 2473 15 can can MD cord-014597-66vd2mdu 2473 16 be be VB cord-014597-66vd2mdu 2473 17 done do VBN cord-014597-66vd2mdu 2473 18 in in IN cord-014597-66vd2mdu 2473 19 a a DT cord-014597-66vd2mdu 2473 20 secure secure JJ cord-014597-66vd2mdu 2473 21 cloud cloud NN cord-014597-66vd2mdu 2473 22 . . . cord-014597-66vd2mdu 2474 1 The the DT cord-014597-66vd2mdu 2474 2 service service NN cord-014597-66vd2mdu 2474 3 can can MD cord-014597-66vd2mdu 2474 4 be be VB cord-014597-66vd2mdu 2474 5 used use VBN cord-014597-66vd2mdu 2474 6 for for IN cord-014597-66vd2mdu 2474 7 single single JJ cord-014597-66vd2mdu 2474 8 experiments experiment NNS cord-014597-66vd2mdu 2474 9 in in IN cord-014597-66vd2mdu 2474 10 low low JJ cord-014597-66vd2mdu 2474 11 throughput throughput NN cord-014597-66vd2mdu 2474 12 applications application NNS cord-014597-66vd2mdu 2474 13 and and CC cord-014597-66vd2mdu 2474 14 is be VBZ cord-014597-66vd2mdu 2474 15 therefore therefore RB cord-014597-66vd2mdu 2474 16 a a DT cord-014597-66vd2mdu 2474 17 benefit benefit NN cord-014597-66vd2mdu 2474 18 for for IN cord-014597-66vd2mdu 2474 19 labs lab NNS cord-014597-66vd2mdu 2474 20 which which WDT cord-014597-66vd2mdu 2474 21 can can MD cord-014597-66vd2mdu 2474 22 not not RB cord-014597-66vd2mdu 2474 23 afford afford VB cord-014597-66vd2mdu 2474 24 automated automate VBN cord-014597-66vd2mdu 2474 25 infrastructure infrastructure NN cord-014597-66vd2mdu 2474 26 or or CC cord-014597-66vd2mdu 2474 27 the the DT cord-014597-66vd2mdu 2474 28 staff staff NN cord-014597-66vd2mdu 2474 29 for for IN cord-014597-66vd2mdu 2474 30 the the DT cord-014597-66vd2mdu 2474 31 maintenance maintenance NN cord-014597-66vd2mdu 2474 32 for for IN cord-014597-66vd2mdu 2474 33 such such JJ cord-014597-66vd2mdu 2474 34 platforms platform NNS cord-014597-66vd2mdu 2474 35 . . . cord-014597-66vd2mdu 2475 1 Extensive extensive JJ cord-014597-66vd2mdu 2475 2 monitoring monitoring NN cord-014597-66vd2mdu 2475 3 and and CC cord-014597-66vd2mdu 2475 4 data datum NNS cord-014597-66vd2mdu 2475 5 capturing capture VBG cord-014597-66vd2mdu 2475 6 during during IN cord-014597-66vd2mdu 2475 7 the the DT cord-014597-66vd2mdu 2475 8 run run NN cord-014597-66vd2mdu 2475 9 leads lead VBZ cord-014597-66vd2mdu 2475 10 to to IN cord-014597-66vd2mdu 2475 11 a a DT cord-014597-66vd2mdu 2475 12 gapless gapless JJ cord-014597-66vd2mdu 2475 13 data data NN cord-014597-66vd2mdu 2475 14 trail trail NN cord-014597-66vd2mdu 2475 15 and and CC cord-014597-66vd2mdu 2475 16 the the DT cord-014597-66vd2mdu 2475 17 possibility possibility NN cord-014597-66vd2mdu 2475 18 of of IN cord-014597-66vd2mdu 2475 19 detailed detailed JJ cord-014597-66vd2mdu 2475 20 result result NN cord-014597-66vd2mdu 2475 21 analysis analysis NN cord-014597-66vd2mdu 2475 22 . . . cord-014597-66vd2mdu 2476 1 Due due IN cord-014597-66vd2mdu 2476 2 to to IN cord-014597-66vd2mdu 2476 3 automated automate VBN cord-014597-66vd2mdu 2476 4 processing processing NN cord-014597-66vd2mdu 2476 5 the the DT cord-014597-66vd2mdu 2476 6 reproducibility reproducibility NN cord-014597-66vd2mdu 2476 7 is be VBZ cord-014597-66vd2mdu 2476 8 increased increase VBN cord-014597-66vd2mdu 2476 9 associated associate VBN cord-014597-66vd2mdu 2476 10 with with IN cord-014597-66vd2mdu 2476 11 direct direct JJ cord-014597-66vd2mdu 2476 12 reduction reduction NN cord-014597-66vd2mdu 2476 13 of of IN cord-014597-66vd2mdu 2476 14 costs cost NNS cord-014597-66vd2mdu 2476 15 and and CC cord-014597-66vd2mdu 2476 16 time time NN cord-014597-66vd2mdu 2476 17 . . . cord-014597-66vd2mdu 2477 1 The the DT cord-014597-66vd2mdu 2477 2 centralized centralized JJ cord-014597-66vd2mdu 2477 3 service service NN cord-014597-66vd2mdu 2477 4 paired pair VBN cord-014597-66vd2mdu 2477 5 with with IN cord-014597-66vd2mdu 2477 6 specific specific JJ cord-014597-66vd2mdu 2477 7 know know VB cord-014597-66vd2mdu 2477 8 - - HYPH cord-014597-66vd2mdu 2477 9 how how NN cord-014597-66vd2mdu 2477 10 allows allow VBZ cord-014597-66vd2mdu 2477 11 up up RB cord-014597-66vd2mdu 2477 12 - - HYPH cord-014597-66vd2mdu 2477 13 scaling scaling NN cord-014597-66vd2mdu 2477 14 of of IN cord-014597-66vd2mdu 2477 15 processes process NNS cord-014597-66vd2mdu 2477 16 at at IN cord-014597-66vd2mdu 2477 17 any any DT cord-014597-66vd2mdu 2477 18 time time NN cord-014597-66vd2mdu 2477 19 . . . cord-014597-66vd2mdu 2478 1 The the DT cord-014597-66vd2mdu 2478 2 web web NN cord-014597-66vd2mdu 2478 3 - - HYPH cord-014597-66vd2mdu 2478 4 based base VBN cord-014597-66vd2mdu 2478 5 interface interface NN cord-014597-66vd2mdu 2478 6 provides provide VBZ cord-014597-66vd2mdu 2478 7 a a DT cord-014597-66vd2mdu 2478 8 flexible flexible JJ cord-014597-66vd2mdu 2478 9 guidance guidance NN cord-014597-66vd2mdu 2478 10 for for IN cord-014597-66vd2mdu 2478 11 the the DT cord-014597-66vd2mdu 2478 12 user user NN cord-014597-66vd2mdu 2478 13 and and CC cord-014597-66vd2mdu 2478 14 the the DT cord-014597-66vd2mdu 2478 15 online online JJ cord-014597-66vd2mdu 2478 16 order order NN cord-014597-66vd2mdu 2478 17 gives give VBZ cord-014597-66vd2mdu 2478 18 24/7 24/7 RP cord-014597-66vd2mdu 2478 19 access access NN cord-014597-66vd2mdu 2478 20 on on IN cord-014597-66vd2mdu 2478 21 the the DT cord-014597-66vd2mdu 2478 22 infrastructure infrastructure NN cord-014597-66vd2mdu 2478 23 , , , cord-014597-66vd2mdu 2478 24 leading lead VBG cord-014597-66vd2mdu 2478 25 to to IN cord-014597-66vd2mdu 2478 26 a a DT cord-014597-66vd2mdu 2478 27 fast fast JJ cord-014597-66vd2mdu 2478 28 reliable reliable JJ cord-014597-66vd2mdu 2478 29 result result NN cord-014597-66vd2mdu 2478 30 generation generation NN cord-014597-66vd2mdu 2478 31 . . . cord-014597-66vd2mdu 2479 1 Furthermore furthermore RB cord-014597-66vd2mdu 2479 2 the the DT cord-014597-66vd2mdu 2479 3 secure secure JJ cord-014597-66vd2mdu 2479 4 interaction interaction NN cord-014597-66vd2mdu 2479 5 with with IN cord-014597-66vd2mdu 2479 6 additional additional JJ cord-014597-66vd2mdu 2479 7 services service NNS cord-014597-66vd2mdu 2479 8 e.g. e.g. IN cord-014597-66vd2mdu 2479 9 other other JJ cord-014597-66vd2mdu 2479 10 specific specific JJ cord-014597-66vd2mdu 2479 11 data data NN cord-014597-66vd2mdu 2479 12 analysis analysis NN cord-014597-66vd2mdu 2479 13 tool tool NN cord-014597-66vd2mdu 2479 14 is be VBZ cord-014597-66vd2mdu 2479 15 possible possible JJ cord-014597-66vd2mdu 2479 16 . . . cord-014597-66vd2mdu 2480 1 This this DT cord-014597-66vd2mdu 2480 2 dynamic dynamic JJ cord-014597-66vd2mdu 2480 3 access access NN cord-014597-66vd2mdu 2480 4 to to IN cord-014597-66vd2mdu 2480 5 automation automation NN cord-014597-66vd2mdu 2480 6 offers offer VBZ cord-014597-66vd2mdu 2480 7 high high JJ cord-014597-66vd2mdu 2480 8 flexibility flexibility NN cord-014597-66vd2mdu 2480 9 for for IN cord-014597-66vd2mdu 2480 10 low low JJ cord-014597-66vd2mdu 2480 11 throughput throughput NN cord-014597-66vd2mdu 2480 12 experiments experiment NNS cord-014597-66vd2mdu 2480 13 and and CC cord-014597-66vd2mdu 2480 14 will will MD cord-014597-66vd2mdu 2480 15 push push VB cord-014597-66vd2mdu 2480 16 high high JJ cord-014597-66vd2mdu 2480 17 quality quality NN cord-014597-66vd2mdu 2480 18 research research NN cord-014597-66vd2mdu 2480 19 and and CC cord-014597-66vd2mdu 2480 20 drug drug NN cord-014597-66vd2mdu 2480 21 development development NN cord-014597-66vd2mdu 2480 22 in in IN cord-014597-66vd2mdu 2480 23 early early JJ cord-014597-66vd2mdu 2480 24 stage stage NN cord-014597-66vd2mdu 2480 25 . . . cord-014597-66vd2mdu 2481 1 Development development NN cord-014597-66vd2mdu 2481 2 of of IN cord-014597-66vd2mdu 2481 3 alternative alternative JJ cord-014597-66vd2mdu 2481 4 animal animal NN cord-014597-66vd2mdu 2481 5 cell cell NN cord-014597-66vd2mdu 2481 6 technology technology NN cord-014597-66vd2mdu 2481 7 platforms platform NNS cord-014597-66vd2mdu 2481 8 : : : cord-014597-66vd2mdu 2482 1 CHO CHO NNP cord-014597-66vd2mdu 2482 2 based base VBN cord-014597-66vd2mdu 2482 3 cell cell NN cord-014597-66vd2mdu 2482 4 - - HYPH cord-014597-66vd2mdu 2482 5 free free JJ cord-014597-66vd2mdu 2482 6 protein protein NN cord-014597-66vd2mdu 2482 7 synthesis synthesis NN cord-014597-66vd2mdu 2482 8 systems system NNS cord-014597-66vd2mdu 2482 9 for for IN cord-014597-66vd2mdu 2482 10 the the DT cord-014597-66vd2mdu 2482 11 production production NN cord-014597-66vd2mdu 2482 12 of of IN cord-014597-66vd2mdu 2482 13 " " `` cord-014597-66vd2mdu 2482 14 difficult difficult JJ cord-014597-66vd2mdu 2482 15 - - HYPH cord-014597-66vd2mdu 2482 16 to to TO cord-014597-66vd2mdu 2482 17 - - HYPH cord-014597-66vd2mdu 2482 18 express express VB cord-014597-66vd2mdu 2482 19 " " '' cord-014597-66vd2mdu 2482 20 proteins protein NNS cord-014597-66vd2mdu 2482 21 Lena Lena NNP cord-014597-66vd2mdu 2482 22 Thoring Thoring NNP cord-014597-66vd2mdu 2482 23 1 1 CD cord-014597-66vd2mdu 2482 24 , , , cord-014597-66vd2mdu 2483 1 2 2 LS cord-014597-66vd2mdu 2483 2 Background Background NNP cord-014597-66vd2mdu 2483 3 Nowadays nowadays RB cord-014597-66vd2mdu 2483 4 , , , cord-014597-66vd2mdu 2483 5 animal animal NN cord-014597-66vd2mdu 2483 6 cell cell NN cord-014597-66vd2mdu 2483 7 technologies technology NNS cord-014597-66vd2mdu 2483 8 are be VBP cord-014597-66vd2mdu 2483 9 commonly commonly RB cord-014597-66vd2mdu 2483 10 used use VBN cord-014597-66vd2mdu 2483 11 for for IN cord-014597-66vd2mdu 2483 12 a a DT cord-014597-66vd2mdu 2483 13 broad broad JJ cord-014597-66vd2mdu 2483 14 range range NN cord-014597-66vd2mdu 2483 15 of of IN cord-014597-66vd2mdu 2483 16 medical medical JJ cord-014597-66vd2mdu 2483 17 and and CC cord-014597-66vd2mdu 2483 18 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 2483 19 applications application NNS cord-014597-66vd2mdu 2483 20 . . . cord-014597-66vd2mdu 2484 1 One one CD cord-014597-66vd2mdu 2484 2 main main JJ cord-014597-66vd2mdu 2484 3 topic topic NN cord-014597-66vd2mdu 2484 4 of of IN cord-014597-66vd2mdu 2484 5 these these DT cord-014597-66vd2mdu 2484 6 technologies technology NNS cord-014597-66vd2mdu 2484 7 is be VBZ cord-014597-66vd2mdu 2484 8 the the DT cord-014597-66vd2mdu 2484 9 production production NN cord-014597-66vd2mdu 2484 10 of of IN cord-014597-66vd2mdu 2484 11 proteins protein NNS cord-014597-66vd2mdu 2484 12 used use VBN cord-014597-66vd2mdu 2484 13 for for IN cord-014597-66vd2mdu 2484 14 therapeutical therapeutical JJ cord-014597-66vd2mdu 2484 15 purposes purpose NNS cord-014597-66vd2mdu 2484 16 . . . cord-014597-66vd2mdu 2485 1 These these DT cord-014597-66vd2mdu 2485 2 in in IN cord-014597-66vd2mdu 2485 3 vivo vivo NN cord-014597-66vd2mdu 2485 4 production production NN cord-014597-66vd2mdu 2485 5 processes process NNS cord-014597-66vd2mdu 2485 6 are be VBP cord-014597-66vd2mdu 2485 7 often often RB cord-014597-66vd2mdu 2485 8 time time NN cord-014597-66vd2mdu 2485 9 consuming consume VBG cord-014597-66vd2mdu 2485 10 and and CC cord-014597-66vd2mdu 2485 11 limited limit VBN cord-014597-66vd2mdu 2485 12 in in IN cord-014597-66vd2mdu 2485 13 production production NN cord-014597-66vd2mdu 2485 14 of of IN cord-014597-66vd2mdu 2485 15 so so RB cord-014597-66vd2mdu 2485 16 called call VBN cord-014597-66vd2mdu 2485 17 " " `` cord-014597-66vd2mdu 2485 18 difficult difficult JJ cord-014597-66vd2mdu 2485 19 - - HYPH cord-014597-66vd2mdu 2485 20 to to TO cord-014597-66vd2mdu 2485 21 - - HYPH cord-014597-66vd2mdu 2485 22 express express VB cord-014597-66vd2mdu 2485 23 " " '' cord-014597-66vd2mdu 2485 24 proteins protein NNS cord-014597-66vd2mdu 2485 25 including include VBG cord-014597-66vd2mdu 2485 26 the the DT cord-014597-66vd2mdu 2485 27 pharmaceutical pharmaceutical JJ cord-014597-66vd2mdu 2485 28 relevant relevant JJ cord-014597-66vd2mdu 2485 29 class class NN cord-014597-66vd2mdu 2485 30 of of IN cord-014597-66vd2mdu 2485 31 membrane membrane NN cord-014597-66vd2mdu 2485 32 proteins protein NNS cord-014597-66vd2mdu 2485 33 . . . cord-014597-66vd2mdu 2486 1 To to TO cord-014597-66vd2mdu 2486 2 overcome overcome VB cord-014597-66vd2mdu 2486 3 these these DT cord-014597-66vd2mdu 2486 4 issues issue NNS cord-014597-66vd2mdu 2486 5 , , , cord-014597-66vd2mdu 2486 6 novel novel JJ cord-014597-66vd2mdu 2486 7 cell cell NN cord-014597-66vd2mdu 2486 8 - - HYPH cord-014597-66vd2mdu 2486 9 free free JJ cord-014597-66vd2mdu 2486 10 protein protein NN cord-014597-66vd2mdu 2486 11 synthesis synthesis NN cord-014597-66vd2mdu 2486 12 platforms platform NNS cord-014597-66vd2mdu 2486 13 were be VBD cord-014597-66vd2mdu 2486 14 developed develop VBN cord-014597-66vd2mdu 2486 15 based base VBN cord-014597-66vd2mdu 2486 16 on on IN cord-014597-66vd2mdu 2486 17 the the DT cord-014597-66vd2mdu 2486 18 industrial industrial JJ cord-014597-66vd2mdu 2486 19 working working NN cord-014597-66vd2mdu 2486 20 horse horse NN cord-014597-66vd2mdu 2486 21 CHO CHO NNP cord-014597-66vd2mdu 2486 22 cells cell NNS cord-014597-66vd2mdu 2486 23 [ [ -LRB- cord-014597-66vd2mdu 2486 24 1 1 CD cord-014597-66vd2mdu 2486 25 ] ] -RRB- cord-014597-66vd2mdu 2486 26 . . . cord-014597-66vd2mdu 2487 1 Cell cell NN cord-014597-66vd2mdu 2487 2 lysates lysate NNS cord-014597-66vd2mdu 2487 3 provide provide VBP cord-014597-66vd2mdu 2487 4 a a DT cord-014597-66vd2mdu 2487 5 basis basis NN cord-014597-66vd2mdu 2487 6 for for IN cord-014597-66vd2mdu 2487 7 this this DT cord-014597-66vd2mdu 2487 8 technology technology NN cord-014597-66vd2mdu 2487 9 by by IN cord-014597-66vd2mdu 2487 10 including include VBG cord-014597-66vd2mdu 2487 11 all all DT cord-014597-66vd2mdu 2487 12 components component NNS cord-014597-66vd2mdu 2487 13 of of IN cord-014597-66vd2mdu 2487 14 the the DT cord-014597-66vd2mdu 2487 15 translational translational JJ cord-014597-66vd2mdu 2487 16 machinery machinery NN cord-014597-66vd2mdu 2487 17 and and CC cord-014597-66vd2mdu 2487 18 enabling enable VBG cord-014597-66vd2mdu 2487 19 protein protein NN cord-014597-66vd2mdu 2487 20 production production NN cord-014597-66vd2mdu 2487 21 within within IN cord-014597-66vd2mdu 2487 22 a a DT cord-014597-66vd2mdu 2487 23 few few JJ cord-014597-66vd2mdu 2487 24 hours hour NNS cord-014597-66vd2mdu 2487 25 . . . cord-014597-66vd2mdu 2488 1 Microsomal Microsomal NNP cord-014597-66vd2mdu 2488 2 structures structure NNS cord-014597-66vd2mdu 2488 3 present present JJ cord-014597-66vd2mdu 2488 4 in in IN cord-014597-66vd2mdu 2488 5 CHO CHO NNP cord-014597-66vd2mdu 2488 6 cell cell NN cord-014597-66vd2mdu 2488 7 lysates lysate NNS cord-014597-66vd2mdu 2488 8 enable enable VBP cord-014597-66vd2mdu 2488 9 posttranslational posttranslational JJ cord-014597-66vd2mdu 2488 10 modification modification NN cord-014597-66vd2mdu 2488 11 of of IN cord-014597-66vd2mdu 2488 12 target target NN cord-014597-66vd2mdu 2488 13 proteins protein NNS cord-014597-66vd2mdu 2488 14 and and CC cord-014597-66vd2mdu 2488 15 insertion insertion NN cord-014597-66vd2mdu 2488 16 of of IN cord-014597-66vd2mdu 2488 17 membrane membrane NN cord-014597-66vd2mdu 2488 18 proteins protein NNS cord-014597-66vd2mdu 2488 19 into into IN cord-014597-66vd2mdu 2488 20 lipid lipid NN cord-014597-66vd2mdu 2488 21 bilayer bilayer NN cord-014597-66vd2mdu 2488 22 . . . cord-014597-66vd2mdu 2489 1 In in IN cord-014597-66vd2mdu 2489 2 this this DT cord-014597-66vd2mdu 2489 3 study study NN cord-014597-66vd2mdu 2489 4 a a DT cord-014597-66vd2mdu 2489 5 cell cell NN cord-014597-66vd2mdu 2489 6 - - HYPH cord-014597-66vd2mdu 2489 7 free free JJ cord-014597-66vd2mdu 2489 8 protein protein NN cord-014597-66vd2mdu 2489 9 synthesis synthesis NN cord-014597-66vd2mdu 2489 10 platform platform NN cord-014597-66vd2mdu 2489 11 was be VBD cord-014597-66vd2mdu 2489 12 developed develop VBN cord-014597-66vd2mdu 2489 13 based base VBN cord-014597-66vd2mdu 2489 14 on on IN cord-014597-66vd2mdu 2489 15 a a DT cord-014597-66vd2mdu 2489 16 combination combination NN cord-014597-66vd2mdu 2489 17 of of IN cord-014597-66vd2mdu 2489 18 CHO CHO NNP cord-014597-66vd2mdu 2489 19 cell cell NN cord-014597-66vd2mdu 2489 20 lysates lysate NNS cord-014597-66vd2mdu 2489 21 and and CC cord-014597-66vd2mdu 2489 22 a a DT cord-014597-66vd2mdu 2489 23 continuous continuous JJ cord-014597-66vd2mdu 2489 24 exchange exchange NN cord-014597-66vd2mdu 2489 25 reaction reaction NN cord-014597-66vd2mdu 2489 26 format format NN cord-014597-66vd2mdu 2489 27 . . . cord-014597-66vd2mdu 2490 1 The the DT cord-014597-66vd2mdu 2490 2 continuous continuous JJ cord-014597-66vd2mdu 2490 3 exchange exchange NN cord-014597-66vd2mdu 2490 4 reactor reactor NN cord-014597-66vd2mdu 2490 5 consists consist VBZ cord-014597-66vd2mdu 2490 6 of of IN cord-014597-66vd2mdu 2490 7 a a DT cord-014597-66vd2mdu 2490 8 twochamber twochamber NN cord-014597-66vd2mdu 2490 9 system system NN cord-014597-66vd2mdu 2490 10 , , , cord-014597-66vd2mdu 2490 11 a a DT cord-014597-66vd2mdu 2490 12 reaction reaction NN cord-014597-66vd2mdu 2490 13 and and CC cord-014597-66vd2mdu 2490 14 a a DT cord-014597-66vd2mdu 2490 15 feeding feeding NN cord-014597-66vd2mdu 2490 16 chamber chamber NN cord-014597-66vd2mdu 2490 17 , , , cord-014597-66vd2mdu 2490 18 separated separate VBN cord-014597-66vd2mdu 2490 19 by by IN cord-014597-66vd2mdu 2490 20 a a DT cord-014597-66vd2mdu 2490 21 semipermeable semipermeable JJ cord-014597-66vd2mdu 2490 22 membrane membrane NN cord-014597-66vd2mdu 2490 23 . . . cord-014597-66vd2mdu 2491 1 Due due IN cord-014597-66vd2mdu 2491 2 to to IN cord-014597-66vd2mdu 2491 3 concentration concentration NN cord-014597-66vd2mdu 2491 4 gradients gradient NNS cord-014597-66vd2mdu 2491 5 , , , cord-014597-66vd2mdu 2491 6 energy energy NN cord-014597-66vd2mdu 2491 7 components component NNS cord-014597-66vd2mdu 2491 8 can can MD cord-014597-66vd2mdu 2491 9 diffuse diffuse VB cord-014597-66vd2mdu 2491 10 to to IN cord-014597-66vd2mdu 2491 11 the the DT cord-014597-66vd2mdu 2491 12 reaction reaction NN cord-014597-66vd2mdu 2491 13 chamber chamber NN cord-014597-66vd2mdu 2491 14 , , , cord-014597-66vd2mdu 2491 15 while while IN cord-014597-66vd2mdu 2491 16 inhibitory inhibitory JJ cord-014597-66vd2mdu 2491 17 byproducts byproduct NNS cord-014597-66vd2mdu 2491 18 are be VBP cord-014597-66vd2mdu 2491 19 continuously continuously RB cord-014597-66vd2mdu 2491 20 removed remove VBN cord-014597-66vd2mdu 2491 21 . . . cord-014597-66vd2mdu 2492 1 Different different JJ cord-014597-66vd2mdu 2492 2 classes class NNS cord-014597-66vd2mdu 2492 3 of of IN cord-014597-66vd2mdu 2492 4 proteins protein NNS cord-014597-66vd2mdu 2492 5 were be VBD cord-014597-66vd2mdu 2492 6 selected select VBN cord-014597-66vd2mdu 2492 7 to to TO cord-014597-66vd2mdu 2492 8 evaluate evaluate VB cord-014597-66vd2mdu 2492 9 the the DT cord-014597-66vd2mdu 2492 10 quality quality NN cord-014597-66vd2mdu 2492 11 of of IN cord-014597-66vd2mdu 2492 12 the the DT cord-014597-66vd2mdu 2492 13 CHO CHO NNP cord-014597-66vd2mdu 2492 14 CECF CECF NNP cord-014597-66vd2mdu 2492 15 system system NN cord-014597-66vd2mdu 2492 16 including include VBG cord-014597-66vd2mdu 2492 17 a a DT cord-014597-66vd2mdu 2492 18 transmembrane transmembrane NN cord-014597-66vd2mdu 2492 19 receptor receptor NN cord-014597-66vd2mdu 2492 20 , , , cord-014597-66vd2mdu 2492 21 a a DT cord-014597-66vd2mdu 2492 22 single single JJ cord-014597-66vd2mdu 2492 23 chain chain NN cord-014597-66vd2mdu 2492 24 variable variable NN cord-014597-66vd2mdu 2492 25 fragment fragment NN cord-014597-66vd2mdu 2492 26 and and CC cord-014597-66vd2mdu 2492 27 an an DT cord-014597-66vd2mdu 2492 28 ion ion NN cord-014597-66vd2mdu 2492 29 channel channel NN cord-014597-66vd2mdu 2492 30 . . . cord-014597-66vd2mdu 2493 1 Cell cell NN cord-014597-66vd2mdu 2493 2 - - HYPH cord-014597-66vd2mdu 2493 3 free free JJ cord-014597-66vd2mdu 2493 4 protein protein NN cord-014597-66vd2mdu 2493 5 synthesis synthesis NN cord-014597-66vd2mdu 2493 6 was be VBD cord-014597-66vd2mdu 2493 7 performed perform VBN cord-014597-66vd2mdu 2493 8 in in IN cord-014597-66vd2mdu 2493 9 the the DT cord-014597-66vd2mdu 2493 10 presence presence NN cord-014597-66vd2mdu 2493 11 of of IN cord-014597-66vd2mdu 2493 12 14 14 CD cord-014597-66vd2mdu 2493 13 C c NN cord-014597-66vd2mdu 2493 14 leucine leucine NN cord-014597-66vd2mdu 2493 15 for for IN cord-014597-66vd2mdu 2493 16 radio radio NN cord-014597-66vd2mdu 2493 17 labeling labeling NN cord-014597-66vd2mdu 2493 18 of of IN cord-014597-66vd2mdu 2493 19 synthesized synthesize VBN cord-014597-66vd2mdu 2493 20 proteins protein NNS cord-014597-66vd2mdu 2493 21 . . . cord-014597-66vd2mdu 2494 1 Protein protein NN cord-014597-66vd2mdu 2494 2 yield yield NN cord-014597-66vd2mdu 2494 3 was be VBD cord-014597-66vd2mdu 2494 4 quantified quantify VBN cord-014597-66vd2mdu 2494 5 by by IN cord-014597-66vd2mdu 2494 6 TCA TCA NNP cord-014597-66vd2mdu 2494 7 precipitation precipitation NN cord-014597-66vd2mdu 2494 8 of of IN cord-014597-66vd2mdu 2494 9 radio radio NN cord-014597-66vd2mdu 2494 10 labeled label VBN cord-014597-66vd2mdu 2494 11 proteins protein NNS cord-014597-66vd2mdu 2494 12 followed follow VBN cord-014597-66vd2mdu 2494 13 by by IN cord-014597-66vd2mdu 2494 14 scintillation scintillation NN cord-014597-66vd2mdu 2494 15 measurement measurement NN cord-014597-66vd2mdu 2494 16 and and CC cord-014597-66vd2mdu 2494 17 molecular molecular JJ cord-014597-66vd2mdu 2494 18 mass mass NN cord-014597-66vd2mdu 2494 19 was be VBD cord-014597-66vd2mdu 2494 20 detected detect VBN cord-014597-66vd2mdu 2494 21 by by IN cord-014597-66vd2mdu 2494 22 autoradiography autoradiography NNP cord-014597-66vd2mdu 2494 23 . . . cord-014597-66vd2mdu 2495 1 Posttranslational posttranslational JJ cord-014597-66vd2mdu 2495 2 modifications modification NNS cord-014597-66vd2mdu 2495 3 and and CC cord-014597-66vd2mdu 2495 4 activities activity NNS cord-014597-66vd2mdu 2495 5 of of IN cord-014597-66vd2mdu 2495 6 proteins protein NNS cord-014597-66vd2mdu 2495 7 were be VBD cord-014597-66vd2mdu 2495 8 estimated estimate VBN cord-014597-66vd2mdu 2495 9 by by IN cord-014597-66vd2mdu 2495 10 kinase kinase NN cord-014597-66vd2mdu 2495 11 assays assay NNS cord-014597-66vd2mdu 2495 12 , , , cord-014597-66vd2mdu 2495 13 ELISA ELISA NNP cord-014597-66vd2mdu 2495 14 , , , cord-014597-66vd2mdu 2495 15 endoglycosidase endoglycosidase NN cord-014597-66vd2mdu 2495 16 treatment treatment NN cord-014597-66vd2mdu 2495 17 and and CC cord-014597-66vd2mdu 2495 18 electrophysiological electrophysiological JJ cord-014597-66vd2mdu 2495 19 measurements measurement NNS cord-014597-66vd2mdu 2495 20 . . . cord-014597-66vd2mdu 2496 1 The the DT cord-014597-66vd2mdu 2496 2 demonstrated demonstrate VBN cord-014597-66vd2mdu 2496 3 results result NNS cord-014597-66vd2mdu 2496 4 showed show VBD cord-014597-66vd2mdu 2496 5 a a DT cord-014597-66vd2mdu 2496 6 protein protein NN cord-014597-66vd2mdu 2496 7 production production NN cord-014597-66vd2mdu 2496 8 of of IN cord-014597-66vd2mdu 2496 9 up up IN cord-014597-66vd2mdu 2496 10 to to IN cord-014597-66vd2mdu 2496 11 around around IN cord-014597-66vd2mdu 2496 12 1 1 CD cord-014597-66vd2mdu 2496 13 g g NN cord-014597-66vd2mdu 2496 14 / / SYM cord-014597-66vd2mdu 2496 15 l l NN cord-014597-66vd2mdu 2496 16 while while IN cord-014597-66vd2mdu 2496 17 detecting detect VBG cord-014597-66vd2mdu 2496 18 correct correct JJ cord-014597-66vd2mdu 2496 19 molecular molecular JJ cord-014597-66vd2mdu 2496 20 weights weight NNS cord-014597-66vd2mdu 2496 21 by by IN cord-014597-66vd2mdu 2496 22 autoradiography autoradiography NNP cord-014597-66vd2mdu 2496 23 . . . cord-014597-66vd2mdu 2497 1 Analysis analysis NN cord-014597-66vd2mdu 2497 2 of of IN cord-014597-66vd2mdu 2497 3 the the DT cord-014597-66vd2mdu 2497 4 productivity productivity NN cord-014597-66vd2mdu 2497 5 using use VBG cord-014597-66vd2mdu 2497 6 different different JJ cord-014597-66vd2mdu 2497 7 lysate lysate NN cord-014597-66vd2mdu 2497 8 batches batch NNS cord-014597-66vd2mdu 2497 9 by by IN cord-014597-66vd2mdu 2497 10 the the DT cord-014597-66vd2mdu 2497 11 production production NN cord-014597-66vd2mdu 2497 12 of of IN cord-014597-66vd2mdu 2497 13 the the DT cord-014597-66vd2mdu 2497 14 membrane membrane NN cord-014597-66vd2mdu 2497 15 protein protein NN cord-014597-66vd2mdu 2497 16 EGFR EGFR NNP cord-014597-66vd2mdu 2497 17 revealed reveal VBD cord-014597-66vd2mdu 2497 18 only only RB cord-014597-66vd2mdu 2497 19 minimal minimal JJ cord-014597-66vd2mdu 2497 20 batch batch NN cord-014597-66vd2mdu 2497 21 - - HYPH cord-014597-66vd2mdu 2497 22 to to IN cord-014597-66vd2mdu 2497 23 - - HYPH cord-014597-66vd2mdu 2497 24 batch batch NN cord-014597-66vd2mdu 2497 25 variations variation NNS cord-014597-66vd2mdu 2497 26 ( ( -LRB- cord-014597-66vd2mdu 2497 27 Fig Fig NNP cord-014597-66vd2mdu 2497 28 . . . cord-014597-66vd2mdu 2497 29 1a 1a CD cord-014597-66vd2mdu 2497 30 ) ) -RRB- cord-014597-66vd2mdu 2497 31 . . . cord-014597-66vd2mdu 2498 1 Posttranslational posttranslational JJ cord-014597-66vd2mdu 2498 2 modifications modification NNS cord-014597-66vd2mdu 2498 3 of of IN cord-014597-66vd2mdu 2498 4 proteins protein NNS cord-014597-66vd2mdu 2498 5 , , , cord-014597-66vd2mdu 2498 6 including include VBG cord-014597-66vd2mdu 2498 7 phosphorylation phosphorylation NN cord-014597-66vd2mdu 2498 8 and and CC cord-014597-66vd2mdu 2498 9 glycosylation glycosylation NN cord-014597-66vd2mdu 2498 10 , , , cord-014597-66vd2mdu 2498 11 were be VBD cord-014597-66vd2mdu 2498 12 detected detect VBN cord-014597-66vd2mdu 2498 13 using use VBG cord-014597-66vd2mdu 2498 14 western western JJ cord-014597-66vd2mdu 2498 15 blot blot NN cord-014597-66vd2mdu 2498 16 and and CC cord-014597-66vd2mdu 2498 17 autoradiography autoradiography NN cord-014597-66vd2mdu 2498 18 ( ( -LRB- cord-014597-66vd2mdu 2498 19 Fig Fig NNP cord-014597-66vd2mdu 2498 20 . . . cord-014597-66vd2mdu 2498 21 1b 1b CD cord-014597-66vd2mdu 2498 22 ) ) -RRB- cord-014597-66vd2mdu 2498 23 . . . cord-014597-66vd2mdu 2499 1 Evaluation evaluation NN cord-014597-66vd2mdu 2499 2 of of IN cord-014597-66vd2mdu 2499 3 localization localization NN cord-014597-66vd2mdu 2499 4 of of IN cord-014597-66vd2mdu 2499 5 membrane membrane NN cord-014597-66vd2mdu 2499 6 embedded embed VBN cord-014597-66vd2mdu 2499 7 eYFP eYFP NNP cord-014597-66vd2mdu 2499 8 fusion fusion NN cord-014597-66vd2mdu 2499 9 proteins protein NNS cord-014597-66vd2mdu 2499 10 by by IN cord-014597-66vd2mdu 2499 11 confocal confocal JJ cord-014597-66vd2mdu 2499 12 laser laser NN cord-014597-66vd2mdu 2499 13 scanning scanning NN cord-014597-66vd2mdu 2499 14 microscopy microscopy NNS cord-014597-66vd2mdu 2499 15 resulted result VBN cord-014597-66vd2mdu 2499 16 in in IN cord-014597-66vd2mdu 2499 17 the the DT cord-014597-66vd2mdu 2499 18 detection detection NN cord-014597-66vd2mdu 2499 19 of of IN cord-014597-66vd2mdu 2499 20 proteins protein NNS cord-014597-66vd2mdu 2499 21 in in IN cord-014597-66vd2mdu 2499 22 the the DT cord-014597-66vd2mdu 2499 23 microsomal microsomal NNP cord-014597-66vd2mdu 2499 24 fraction fraction NN cord-014597-66vd2mdu 2499 25 of of IN cord-014597-66vd2mdu 2499 26 CHO CHO NNP cord-014597-66vd2mdu 2499 27 cell cell NN cord-014597-66vd2mdu 2499 28 lysate lysate NN cord-014597-66vd2mdu 2499 29 . . . cord-014597-66vd2mdu 2500 1 Produced produce VBN cord-014597-66vd2mdu 2500 2 single single JJ cord-014597-66vd2mdu 2500 3 chain chain NN cord-014597-66vd2mdu 2500 4 variable variable NN cord-014597-66vd2mdu 2500 5 fragments fragment NNS cord-014597-66vd2mdu 2500 6 showed show VBD cord-014597-66vd2mdu 2500 7 binding bind VBG cord-014597-66vd2mdu 2500 8 specificity specificity NN cord-014597-66vd2mdu 2500 9 in in IN cord-014597-66vd2mdu 2500 10 ELISA ELISA NNP cord-014597-66vd2mdu 2500 11 experiments experiment NNS cord-014597-66vd2mdu 2500 12 . . . cord-014597-66vd2mdu 2501 1 The the DT cord-014597-66vd2mdu 2501 2 activity activity NN cord-014597-66vd2mdu 2501 3 of of IN cord-014597-66vd2mdu 2501 4 synthesized synthesize VBN cord-014597-66vd2mdu 2501 5 ion ion NN cord-014597-66vd2mdu 2501 6 channels channel NNS cord-014597-66vd2mdu 2501 7 was be VBD cord-014597-66vd2mdu 2501 8 underlined underline VBN cord-014597-66vd2mdu 2501 9 by by IN cord-014597-66vd2mdu 2501 10 electrophysiological electrophysiological JJ cord-014597-66vd2mdu 2501 11 measurements measurement NNS cord-014597-66vd2mdu 2501 12 and and CC cord-014597-66vd2mdu 2501 13 detected detect VBD cord-014597-66vd2mdu 2501 14 single single JJ cord-014597-66vd2mdu 2501 15 channel channel NN cord-014597-66vd2mdu 2501 16 activities activity NNS cord-014597-66vd2mdu 2501 17 . . . cord-014597-66vd2mdu 2502 1 A a DT cord-014597-66vd2mdu 2502 2 cell cell NN cord-014597-66vd2mdu 2502 3 - - HYPH cord-014597-66vd2mdu 2502 4 free free JJ cord-014597-66vd2mdu 2502 5 system system NN cord-014597-66vd2mdu 2502 6 based base VBN cord-014597-66vd2mdu 2502 7 on on IN cord-014597-66vd2mdu 2502 8 CHO CHO NNP cord-014597-66vd2mdu 2502 9 cell cell NN cord-014597-66vd2mdu 2502 10 lysates lysate NNS cord-014597-66vd2mdu 2502 11 for for IN cord-014597-66vd2mdu 2502 12 high high JJ cord-014597-66vd2mdu 2502 13 yield yield NN cord-014597-66vd2mdu 2502 14 production production NN cord-014597-66vd2mdu 2502 15 of of IN cord-014597-66vd2mdu 2502 16 proteins protein NNS cord-014597-66vd2mdu 2502 17 was be VBD cord-014597-66vd2mdu 2502 18 developed develop VBN cord-014597-66vd2mdu 2502 19 that that WDT cord-014597-66vd2mdu 2502 20 provides provide VBZ cord-014597-66vd2mdu 2502 21 a a DT cord-014597-66vd2mdu 2502 22 platform platform NN cord-014597-66vd2mdu 2502 23 for for IN cord-014597-66vd2mdu 2502 24 efficient efficient JJ cord-014597-66vd2mdu 2502 25 production production NN cord-014597-66vd2mdu 2502 26 of of IN cord-014597-66vd2mdu 2502 27 " " `` cord-014597-66vd2mdu 2502 28 difficult difficult JJ cord-014597-66vd2mdu 2502 29 - - HYPH cord-014597-66vd2mdu 2502 30 to to TO cord-014597-66vd2mdu 2502 31 - - HYPH cord-014597-66vd2mdu 2502 32 express express VB cord-014597-66vd2mdu 2502 33 " " '' cord-014597-66vd2mdu 2502 34 proteins protein NNS cord-014597-66vd2mdu 2502 35 . . . cord-014597-66vd2mdu 2503 1 The the DT cord-014597-66vd2mdu 2503 2 combination combination NN cord-014597-66vd2mdu 2503 3 of of IN cord-014597-66vd2mdu 2503 4 a a DT cord-014597-66vd2mdu 2503 5 CHO CHO NNP cord-014597-66vd2mdu 2503 6 lysate lysate NN cord-014597-66vd2mdu 2503 7 based base VBN cord-014597-66vd2mdu 2503 8 cell cell NN cord-014597-66vd2mdu 2503 9 - - HYPH cord-014597-66vd2mdu 2503 10 free free JJ cord-014597-66vd2mdu 2503 11 system system NN cord-014597-66vd2mdu 2503 12 and and CC cord-014597-66vd2mdu 2503 13 a a DT cord-014597-66vd2mdu 2503 14 continuous continuous JJ cord-014597-66vd2mdu 2503 15 exchange exchange NN cord-014597-66vd2mdu 2503 16 cell cell NN cord-014597-66vd2mdu 2503 17 - - HYPH cord-014597-66vd2mdu 2503 18 free free JJ cord-014597-66vd2mdu 2503 19 system system NN cord-014597-66vd2mdu 2503 20 leads lead VBZ cord-014597-66vd2mdu 2503 21 to to TO cord-014597-66vd2mdu 2503 22 be be VB cord-014597-66vd2mdu 2503 23 a a DT cord-014597-66vd2mdu 2503 24 highly highly RB cord-014597-66vd2mdu 2503 25 efficient efficient JJ cord-014597-66vd2mdu 2503 26 production production NN cord-014597-66vd2mdu 2503 27 system system NN cord-014597-66vd2mdu 2503 28 for for IN cord-014597-66vd2mdu 2503 29 various various JJ cord-014597-66vd2mdu 2503 30 classes class NNS cord-014597-66vd2mdu 2503 31 of of IN cord-014597-66vd2mdu 2503 32 " " `` cord-014597-66vd2mdu 2503 33 difficult difficult JJ cord-014597-66vd2mdu 2503 34 - - HYPH cord-014597-66vd2mdu 2503 35 to to TO cord-014597-66vd2mdu 2503 36 - - HYPH cord-014597-66vd2mdu 2503 37 express express VB cord-014597-66vd2mdu 2503 38 " " '' cord-014597-66vd2mdu 2503 39 proteins protein NNS cord-014597-66vd2mdu 2503 40 . . . cord-014597-66vd2mdu 2504 1 This this DT cord-014597-66vd2mdu 2504 2 approach approach NN cord-014597-66vd2mdu 2504 3 opens open VBZ cord-014597-66vd2mdu 2504 4 up up RP cord-014597-66vd2mdu 2504 5 a a DT cord-014597-66vd2mdu 2504 6 fast fast JJ cord-014597-66vd2mdu 2504 7 and and CC cord-014597-66vd2mdu 2504 8 cost cost NN cord-014597-66vd2mdu 2504 9 - - HYPH cord-014597-66vd2mdu 2504 10 effective effective JJ cord-014597-66vd2mdu 2504 11 process process NN cord-014597-66vd2mdu 2504 12 pipeline pipeline NN cord-014597-66vd2mdu 2504 13 for for IN cord-014597-66vd2mdu 2504 14 the the DT cord-014597-66vd2mdu 2504 15 production production NN cord-014597-66vd2mdu 2504 16 of of IN cord-014597-66vd2mdu 2504 17 " " `` cord-014597-66vd2mdu 2504 18 difficult difficult JJ cord-014597-66vd2mdu 2504 19 - - HYPH cord-014597-66vd2mdu 2504 20 to to TO cord-014597-66vd2mdu 2504 21 - - HYPH cord-014597-66vd2mdu 2504 22 express express VB cord-014597-66vd2mdu 2504 23 " " '' cord-014597-66vd2mdu 2504 24 proteins protein NNS cord-014597-66vd2mdu 2504 25 and and CC cord-014597-66vd2mdu 2504 26 shows show VBZ cord-014597-66vd2mdu 2504 27 a a DT cord-014597-66vd2mdu 2504 28 high high JJ cord-014597-66vd2mdu 2504 29 potential potential NN cord-014597-66vd2mdu 2504 30 for for IN cord-014597-66vd2mdu 2504 31 industrial industrial JJ cord-014597-66vd2mdu 2504 32 applications application NNS cord-014597-66vd2mdu 2504 33 including include VBG cord-014597-66vd2mdu 2504 34 screening screening NN cord-014597-66vd2mdu 2504 35 technologies technology NNS cord-014597-66vd2mdu 2504 36 , , , cord-014597-66vd2mdu 2504 37 protein protein NN cord-014597-66vd2mdu 2504 38 structure structure NN cord-014597-66vd2mdu 2504 39 determination determination NN cord-014597-66vd2mdu 2504 40 and and CC cord-014597-66vd2mdu 2504 41 just just RB cord-014597-66vd2mdu 2504 42 - - HYPH cord-014597-66vd2mdu 2504 43 in in IN cord-014597-66vd2mdu 2504 44 - - HYPH cord-014597-66vd2mdu 2504 45 time time NN cord-014597-66vd2mdu 2504 46 protein protein NN cord-014597-66vd2mdu 2504 47 production production NN cord-014597-66vd2mdu 2504 48 processes process NNS cord-014597-66vd2mdu 2504 49 . . .