1430003 1..14 UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) UvA-DARE (Digital Academic Repository) Citation analysis of the scientific publications of Britton Chance in ISI citation indexes Li, L.Z.; Leydesdorff, L.; Nioka, S.; Sun, N.; Garfield, E. DOI 10.1142/S1793545814300031 Publication date 2014 Document Version Final published version Published in Journal of Innovative Optical Health Sciences Link to publication Citation for published version (APA): Li, L. Z., Leydesdorff, L., Nioka, S., Sun, N., & Garfield, E. (2014). Citation analysis of the scientific publications of Britton Chance in ISI citation indexes. 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Download date:06 Apr 2021 https://doi.org/10.1142/S1793545814300031 https://dare.uva.nl/personal/pure/en/publications/citation-analysis-of-the-scientific-publications-of-britton-chance-in-isi-citation-indexes(bf03b40b-d2f1-4484-b3a0-fe942b73c1f3).html https://doi.org/10.1142/S1793545814300031 Citation analysis of the scienti¯c publications of Britton Chance in ISI citation indexes Lin Z. Li*,†,||, Loet Leydesdor®‡, Shoko Nioka†, Nannan Sun*,†, § and Eugene Gar¯eld¶ *Department of Radiology, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA †Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation Department of Biochemistry and Biophysics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA ‡University of Amsterdam Amsterdam School of Communications Research (ASCoR), Netherlands § Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074, P. R. China ¶Institute for Scienti¯c Information — Thomson Reuters Philadelphia, PA 19130, USA ||linli@mail.med.upenn.edu Received 4 March 2014 Accepted 4 March 2014 Published 2 April 2014 Britton Chance was a pioneer in many scienti¯c ¯elds such as enzymatic reaction kinetics, bioenergetics, metabolism, in vivo NMR, and biophotonics. As an engineer, physical chemist, physicist, physiologist, biophysicist, biochemist, innovator and educator, he had worked in diversi¯ed ¯elds over extended periods between 1926 until his death in 2010, at the age of 97. In order to illustrate his scienti¯c career and great impact on research from a new perspective, we employ scientometric analysis tools to analyze the publications of Britton Chance with data downloaded from the ISI Citation Indexes in April 2013. We included articles, reviews and proceeding papers but excluded meeting abstracts. In total, we obtained 1023 publication records with 1236 authors in 266 journals with 17,114 citations from 1945 to 2013. We show the annual publications and citations that Britton Chance received from 1945 to 2013, and generate HistCite maps on the basis of the global citations (GCS) and local (self) citations (LCS) to show the citation relationships among the top-30 publications of Britton Chance. Metabolism and the This is an Open Access article published by World Scienti¯c Publishing Company. It is distributed under the terms of the Creative Commons Attribution 3.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited. Journal of Innovative Optical Health Sciences Vol. 7, No. 2 (2014) 1430003 (14 pages) #.c The Authors DOI: 10.1142/S1793545814300031 1430003-1 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . http://dx.doi.org/10.1142/S1793545814300031 development of physical methods to probe it appear to be the connecting thread of the lifelong research of Britton Chance. Furthermore, we generate the journal map and co-authorship map to show the broad scope of research topics and collaborators and the high impacts of the scienti¯c oeuvre of Britton Chance ranging from physics, engineering, chemistry and biology to medicine. Keywords: Scientometric analysis; impact; HistCite; citation tree; metabolism; mitochondria. 1. Introduction to Britton Chance Britton Chance (1913–2010), one of the most out- standing scientists in the world in the 20th century, had been a legendary ¯gure in the history of science. He was famous for his enthusiasm in sailing due to his family tradition, which brought him the rare experience of catching a big, over 400 lb blue marlin in Caribbean Sea, an Olympic Gold Medal for 5.5 m boat sailing in 1952, and a couple of world cham- pionships of sailing in 1960s. However, his talent, enthusiasm and fame were far more distinguished in science. As a teenager, he invented an optoelectric device for ship autosteering, which was later tested satisfactorily for large commercial ships such as the Texas Sun and New England Star in 1930s. Along with these testing trips, he was admitted to the Trinity College of Cambridge University in late 1930s under the mentorship of Glenn Millikan, the son of the Nobel Laureate Robert A. Millikan, who measured the charge of the electron. Eventually, he graduated with two PhDs, one in Physical Chem- istry from the University of Pennsylvania in 1940, and one in Physiology from the University of Cambridge in 1942. His PhD thesis was on devel- oping a fast mini stop-°ow device for measuring the kinetics of enzymatic reactions. With such a device, he achieved the ¯rst experimental, quantitative demonstration of the existence of Michaelis-Menten enzyme–substrate complex in early 1940s. He was also highly skillful with circuits and electronics. From 1941–1946, he was recruited to the Radiation Lab in MIT for developing advanced radar systems including anti-aircraft radar SCR584 and airborne radar bomber sight used for ¯ghting against Nazi during World War II. He quickly rose to be a member of Steering Committee of the Radiation Lab, leading a large group of physicists with over 200 people. His group taught Presper Eckert how to make key circuits and overcome some technical problems for ENIAC, the world 1st general purpose electronic digital computer at the University of Pennsylvania in 1946. From 1940s till 2010 except a couple of short term leaves, he stayed in the Johnson Research Foundation, Department of Biochemistry and Biophysics at the University of Pennsylvania for seven decades. From 2006 to 2010, he spent half a year annually in research institutions in Asian countries and regions such as Singapore, Mainland China and Taiwan to conduct research and education, helping the development of biopho- tonics in those places. His eight decades of scienti¯c research (1926– 2010) culminated into numerous scienti¯c dis- coveries and technological inventions. He had advanced many frontier research ¯elds at the time with both the development of new methods/devices and their applications to key biological questions. Apart from the aforementioned enzyme kinetics studies with his mini stop-°ow device, in 1950s, Chance invented the dual-wavelength spectropho- tometer which has been widely used for studying turbid biological samples around the world until today. He applied this instrument to extensive in- vestigations on the electron transport in mitochon- drial respiration, redox cofactors and metabolic control mechanisms. In 1960s, he ¯rst discovered the electronic tunneling process in biological sys- tems. In 1970s, he identi¯ed hydrogen peroxide released by the respiratory chain in mitochondria. From 1970s to early 1980s, he developed the 3D cryogenic redox scanner for imaging tissue redox state and its heterogeneity at submillimeter resol- ution. In the 1970–1980s, he was also a key player in developing in vivo31 P-NMR spectroscopy for bioe- nergetics studies and using X-ray spectroscopy to elucidate the structure–function relation of biomo- lecules. Since late 1980s, Prof Chance and his col- laborators had founded the ¯eld of biophotonics by developing in vivo NIR spectroscopy and imaging methods, mainly based on hemoglobin absorption, time-resolved spectroscopy, photon di®usion, etc. These methods have been widely applied in both laboratory and clinic studies for the measurement of blood oxygenation, volume, and °ow, brain activi- ties, muscle functions and cancer detections and diagnosis. The new research directions he developed L. Z. Li et al. 1430003-2 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . during the last decade of his life includes developing novel molecular beacons for cancer diagnosis and therapy, predicting cancer aggressiveness by redox scanning, and developing an oral optical metabol- ometer to detect nutritional status in human sub- jects. The latter two directions completed the circle of his scienti¯c research since 1950s by utilizing intrinsic optical signals from mitochondria. Among many honors and awards1 he has received are the memberships of national academies of sci- ences from six countries including United States, Italy, United Kingdom, Sweden, Germany and Argentina; over 10 honorary PhD and MD degrees; US National Medal of Sciences (1974); The Gold Medal for Distinguished Service to Medicine, College of Physicians, USA (1987); The Gold Medal of the Society of Magnetic Resonance in Medicine, USA (1988); The Benjamin Franklin Medal for Dis- tinguished Achievement in the Sciences, American Philosophical Society (1990); The Christopher Columbus Discovery Award in Biomedical Research, National Institutes of Health, USA (1992); The In- ternational Society for Optical Engineering (SPIE) Lifetime Achievement Award (2005); The Gold Medal of American Roentgen Ray Society (2006); Distinguished Achievement Award of American Aging Association (2006). Due to his tireless e®ort in promoting scienti¯c exchange and collaboration between the East and the West, Chance received the Friendship Award from the State Administration of Foreign Experts A®airs of China in 2008. He was further recognized in 2009 with the International Science and Technology Cooperation Award, which is China's highest national honor given to foreign scientists. In 2013, Chance was inducted into the Innovators Walk of Fame at the University City Science Center, Philadelphia. 2. Scientometric Analysis To commemorate a great scholar and carry on his/ her legacy to future generations, scientometric analysis can be used in addition to anecdotal stories. Scientometric analyses have been utilized to evalu- ate the achievements of scholars,2 and usually these scholars have a focus within a speci¯c ¯eld. Here we employed several tools to evaluate the scienti¯c contribution of Britton Chance whose career span- ning multiple disciplines. Our analysis was based on a dataset downloaded from the ISI Citation Indexes in April, 2013. Articles, reviews and proceeding papers were included with no meeting abstracts. We obtained 1023 publication records in total from 1945 to 2013 including 1236 authors in 266 journals with 17,114 citations. Publication periods. We try to correlate the annual publication pro¯le of Chance with his research activities. In these 67 years between 1945 and 2012 (age 32–97), average of 15.3 papers were published with 255 citations annually. Note that these numbers underestimate his published manu- scripts, because many of his manuscripts were published in places not indexed by ISI Citation Indexes yet. His publications during his graduate studies were not covered by ISI. Moreover, during the time before World War II ended in 1945, he worked in the area of electronic engineering in a secret mission at Radiation Laboratory, thus, most of his works were not published in academic journals. Figure 1 shows the annual number of published manuscripts from 1945–2012. At a glance, there are seven periods of Gaussian distributions over the whole time, and each one seems to represent roughly main subjects of his works. The publi- cations of these periods went up and down, and we found that, for quite a few occasions, the publi- cations of new ideas changed the research direction of Chance and boosted his publication records. The ¯rst Gaussian period (1945–1956, peak at 1952) includes a number of applications of the micro stop-°ow method to enzyme–substrate kinetics3–5 and the development of dual beam spectrometer6 enabling the study of turbid biological samples. With those apparatuses, Chance was active himself in several areas as well as he helped many other research works in various ¯elds of physiology, chemistry, biochemistry, enzymology, etc. In 1947, Chance was the ¯rst to identify catalase compound I as an intermediate in the reaction of hydrogen peroxide and catalase.7 In 1955, he published a landmark paper series with G.R. Williams on res- piratory enzymes in oxidative phosphorylation.8–11 Chance ¯nally set his life work into the mitochon- drial biochemistry. The second period (1957–1968) contains a peak at 1959 with the key publications of Chance's life- long work on metabolic control mechanisms.12–17 The function of mitochondrial energy metabolism was well understood by the kinetic experiments of substrate and products relationships using the Citation analysis of the scienti¯c publications of Britton Chance 1430003-3 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . double beam spectrometer. The peak at 1959 also came after the ¯rst observation of mitochondrial NADH °uorescence18 by him and Baltsche®sky in 1958 and coincided with the ¯rst observation of tissue NADH °uorescence19 by Chance and Jobsis in 1959. Chance et al. published in 1962 the ¯rst in vivo observation of NAD(P)H °uorescence and redox state from the brain and kidney.20–22 As we can see with his work on NADH °uorescence, Chance started with mitochondria followed by tis- sue and in vivo studies. This group of papers laid down a milestone for bioenergetics research and Chance's later work on the translational and clinical studies. From 1962–1968, Chance continued mito- chondrial bioenergetics research on Complex I to IV with optical spectrometers and °uorometers of cytochromes and NADH. His publication peaked again in 1966 coinciding with another landmark discovery by him and DeVoult on the ¯rst exper- imental observation of quantum mechanical electron tunneling in biological system.23 The importance of this work was recognized later on by a conference of the Royal Society on quantum catalysis in enzymes in 2005.24 During the valley of 1967–1968, Chance and coworkers identi¯ed oxidized °avoproteins (Fp including FAD) as another source of intrinsic °uor- escence from mitochondria,25–27 which contributed to another rebound of publications in the following years. The 3rd broad period of Chance publication curve from 1969–1977 appears to have the 2nd largest publication peak with studies ranging from NADH, °avoproteins, cytochoromes, calcium uptake to hydrogen peroxide generation. The use of oxidized °avoproteins together with NADH makes the in vivo measurement of redox status (Fp/NADH or Fp/ (FpþNADH)) possible by the °uorescence spec- troscopy and imaging. Therefore Chance et al. developed this idea and technologies into transla- tional researches by inventing NADH °uorometery, °ying spot technology and cryogenic NADH/Fp redox scanning, etc. Still now, these are the only °uorescence signals used clinically, mainly for can- cer detection. Chance wrote in his unpublished autobiography regarding the importance of his dis- covery of the °uorescence of NADH and Fp from mitochondria both in vivo and ex vivo: \. . .This was perhaps the most important discovery of my career because, for the ¯rst time, we could obtain optical signals from living mitochondrial tissues. A series of papers, exploring this discovery in the liver, kidney, adrenal gland, and brain, opened a new ¯eld of metabolic research. . .." Indeed, since 1950s Chance kept publishing on NADH and Fig. 1. The annual number of publications of Britton Chance from 1945–2012. Graph reproduced from ISI Citation Indexes (accessed in April, 2013 excluding meeting abstracts) with modi¯cations. There were seven periods I–VII as described in the text. L. Z. Li et al. 1430003-4 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . °avoproteins throughout the rest of his life. The work on NADH and °avoproteins, along with his other research work including the studies on cyto- chromes,28–30 discovery of the calcium uptake by mitochondria and its e®ects on bioenergetics,31 discovery of hydrogen peroxide generation by mitochondria,32 etc., really drove the publication of Chance onto a new level in the subsequent years until late 1970s, with about 20 papers annually. The 4th period in 1978–1981 is only 4 years, and it is the beginning of three important new directions of publications. The ¯rst direction of new publi- cations marked the beginning of Chance's e®ort in developing 31P-NMR techniques for bioenergetics studies in organs and human body.33–36 Chance funded himself to make an NMR machine for studying phosphorous energetics in human subjects including his own leg in vivo.33,37 The second new direction of publications was about the chemilumi- nescence38–40 emitted by the lipid peroxidation process in biological systems, which was the con- tinuation of the interest of Chance on metabolism, redox reactions and free radicals. Chance published his studies on chemiluminescence from late 1970s to mid 1990s. He and coworkers probably provided one of the early experimental evidences for the generation of singlet oxygen in biological pro- cesses.41–43 The third source of new publications was the studies44–48 by Chance and Power et al. using synchrotron radiation X-ray spectroscopy to illustrate structure–function relation for biomole- cules including cytochrome oxidase, myoglobin, glyoxalase, etc. The 5th period of Chance publication (1982– 1989) has the highest peak in 1987 with an annual publication of 32 papers. That was on average two papers per three week at the age of 74. That was the period when Chance and Leigh et al. had made signi¯cant progress in developing in vivo NMR for bioenergetics and applying it to diseases. From 1984 to 1987, every year Chance and Leigh coauthored 10–15 papers according to the ISI Science Citation indexes. Other sources of contributions include the chemiluminescence studies and the synchrotron radiation studies aforementioned. After the peak in 1987, Chance publication lowered to 15 in 1990. In 1988, Chance and Leigh et al. initiated time- resolved measurements on hemoglobin and myo- globin in tissues.49,50 Chance then published with M. S. Patterson and B. C. Wilson the work on time- resolved optical spectroscopy,51 which made it possible to measure scattering and absorption coe±cients in biological tissue. This paper was revolutionary for optical ¯elds because it gave birth to the di®usive biomedical photonics. The last two Gaussian periods of Chance publi- cation (1990–1999 and 2000–2010) are truly optical and more translational periods of Chance's work. Chance, as a founding father of modern biopho- tonics, had collaborated with A. Yodh and a num- ber of researchers since 1990s to develop NIR spectroscopy and imaging, including time resolved spectroscopy, photon di®usion tomography (PDT), phased array and their biomedical applications to study brain (fNIR), muscle and various diseases such as breast cancer.52–63 Chance et al. also inte- grated NIR spectroscopy/imaging with magnetic resonance imaging.58,64 Since 2002, Chance had publications with Zheng and Glickson et al. on molecular beacons, nanoparticles and photo- dynamic therapy.65–69 His publication rebounded in 1991 and maintained an average publication of about 18 papers annually for 15 years until 2005. In 2006, Chance ran out of his research funding and since then he was invited to teach and conduct research in Singapore, Mainland China and Taiwan half of the time each year, while Li and Xu were maintaining his redox scanning lab at the Univer- sity of Pennsylvania. His publication went down but was still maintained at about eight papers on average per year until 2010. During this period of time, he and his coworkers investigated on the development of optical imaging biomarkers for cancer diagnosis and tumor metastatic poten- tial,70–73 stem cell stemness74 and a metabol- ometer75 for monitoring human nutritional status. Chance worked on research till the last few days of his life. Li et al. remembered discussing research data with him in the hospital room three days before his passing away. Citation trends. The annual citations of the Chance publications shown in Fig. 2 exhibited 4 rising (R) phases and 2 leveling (L) phases. The 1st rising phase (R1) from 1947 till 1958, increasing with about 20 citations per year, is presumably based on his studies on enzyme kinetics and pio- neering work on oxidative phosphorylation. The phase R2 from 1959 to 1972 has the steepest slope (� 60 citations per year) among the four R phases, indicating his scienti¯c in°uence expanded at the fastest pace during these years. This expansion of fame should be signi¯cantly contributed by his Citation analysis of the scienti¯c publications of Britton Chance 1430003-5 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . previous work on the stop-°ow measurement of enzyme–substrate kinetics. Indeed, \when Manfred Eigen won the [Nobel] prize in 1967 for his tem- perature jump method that could dissect chemical reactions even more ¯nely than Brit's stopped °ow approach, he publicly regretted not being able to share the honor with Britton Chance" (Gottfried Schatz, 2011 http://www.med.upenn.edu/biocbiop/ chance/symposium/schatz/schatz talk.html). For Britton Chance, this was also a period with im- portant new discoveries that were nothing short of importance compared to his ¯rst experimental demonstration of the existence of Michaelis-Menten enzyme–substrate complex. He and his coworkers developed the dual-beam spectrometer for biological studies and characterized theelectron-transport chain and bioenergetic process in mitochondrial oxidative phosphorylation. They discovered the °uorescence of NADH and °avoproteins from mitochondria and translated these methods to tissue in vivo with many clinical applications. They also discovered the electron-tunneling in biological systems, and ident- i¯ed the calcium uptake and hydrogen peroxide generation by mitochondria. In 1974, Britton Chance was awarded the US National Medal of Sciences. The ¯rst leveling phase L1 corresponds to 1973–1976. The third rising R3 phase from 1976 to 1996 includes the original development of phos- phorous NMR and di®usive optical spectroscopy and imaging methods, with a slope similar to that of ¯rst phase, followed by the leveling phase L2 from 1997–2001 with over 1500 citations per year on average. The rising phase R4 is from 2002 to 2012 with a slope of 30 citations per year higher than that of R1 and R3. HistCite analysis. Figures 3 and 4 show the citation analysis results from HistCiteTM for top 30 papers with the highest global citations and local citations, respectively. The local citations refer to the citations only by the papers published by Chance himself. The citation relationships among these papers are displayed in these two ¯gures. The detailed paper information and the number of citations are also listed in the order of publication years from the oldest to the latest. For global citation analysis, there are six papers cited by over 1000 times. The No. 1 highest cited paper76 is a review by Chance et al. in 1979 on hydrogen peroxide metabolism in mammalian organs, with nearly 4000 citations. The fourth highest cited paper77 is also about hydrogen per- oxide, i.e., its generation by mitochondria, general Fig. 2. The annual citations of publications of Britton Chance from 1947–2013. Graph reproduced from ISI Citation Indexes (accessed in April, 2013 excluding meeting abstracts) with modi¯cations. R: rising phase; L: leveling phase as described in the text. L. Z. Li et al. 1430003-6 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . F ig . 3 . C it a ti o n tr ee a n d ta b le fr o m th e g lo b a l ci ta ti o n a n a ly si s o n th e p u b li ca ti o n s o f B ri tt o n C h a n ce b y H is tC it e. T h e a rr o w fr o m A to B in d ic a te s A ci ti n g B . Citation analysis of the scienti¯c publications of Britton Chance 1430003-7 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . F ig . 4 . C it a ti o n tr ee a n d ta b le fr o m th e lo ca l ci ta ti o n a n a ly si s o n th e p u b li ca ti o n s o f B ri tt o n C h a n ce b y H is tC it e. T h e a rr o w fr o m A to B in d ic a te s A ci ti n g B . L. Z. Li et al. 1430003-8 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . Fig. 5. Journal maps of Britton Chance publications. The size of sphere is proportional to number of publications. Fig. 6. Top journals with most publications from Britton Chance. Citation analysis of the scienti¯c publications of Britton Chance 1430003-9 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . properties and e®ects. The second78 and ¯fth8 highest cited papers are both about mitochondrial respirat- ory chain and oxidative phosphorylation. The third highest cited paper79 is about assays of catalases and peroxidases. The sixth highest cited paper51 is about the time-resolved optical spectroscopy marking the beginning of photon-di®usion spec- troscopy and imaging. Among the top 30 globally most cited papers, 4 are about enzyme assay and kinetic studies, 1 about dual beam spectrometer, 13 about mitochondrial oxidative phosphorylation, 5 about NIR imaging and spectroscopy (biophotonics), 1 about in vivo 31P-NMR, 1 about electron tunneling, 1 about calcium ion uptake by mitochondrion, 5 about hydrogen peroxide. For local citation analysis, three of the top six highest globally cited papers remain in the top six. They are two papers on respiratory chain/oxidative phosphorylation8,78 and one on time-resolved opti- cal spectroscopy.51 The other three ranked within Fig. 7. Coauthor maps. All coauthors with more than 1 publication with Britton Chance. The size of sphere is proportional to the number of papers. L. Z. Li et al. 1430003-10 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . the top six locally cited are all on respiratory chain/ oxidative phosphorylation.10,80,81 Among the top 30 locally most cited papers, 4 papers are about enzyme assay and kinetic studies, 1 about dual beam spec- trometer, 16 about mitochondrial respiration and redox state, 1 about calcium ion uptake by mito- chondrion, 5 about NIR imaging and spectroscopy (biophotonics), 4 about in vivo 31P-NMR. It appears that the studies on mitochondrial metabolism and the related development of optical techniques are most-often cited by Chance himself. From the LCS map (Fig. 4) we can see that these work form the center of the citation tree, with biophotonics and NMR bioenergetics as side lobes linked to the center. This relationship indicates mitochondrial metab- olism as a central basis of Chance research rationale and a long-term pursued research goal. During the last 20 years of his life, Chance appeared to have diversi¯ed his research and moved away from this research focus by developing new techniques such as in vivo NIR spectroscopy and imaging. Nevertheless, these new methods, although with many novel ap- plications beyond mitochondrial metabolism, are important for probing and understanding about tis- sue metabolism. Diversity of research ¯elds and collaborators. Figure 5 shows the journal maps of Chance publi- cations. The size of sphere is proportional to the logarithm of the number of publications. Among the 266 journals, Chance has published in this ISI database, the leading journals include Journal of Biological Chemistry, Proceedings of National Academy of Sciences (PNAS), Nature, Review of Scienti¯c Instrumentation, Journal Biomedical Optics, Science, Journal of Applied Physiology, Analytical Biochemistry, New England Journal of Medicine, Physics in Medicine and Biology, Brain Research, Medicine & Science in Sports & Exercise, NMR in Biomedicine, and so on. From these journal titles (only a portion of journal titles shown in Fig. 5), we can see that the research of Chance covered multiple disciplines ranging from physics, engineering, biology to medicine. Figure 6 provides more detailed information about the top 19 journals with most publications from Chance. Impressively there are 92 papers in Journal of Biological Chem- istry, 37 in PNAS, 27 in Nature and 16 in Science. Figure 7 is the coauthor map showing all coauthors with more than 1 publication with Chance. The size of sphere is proportional to the number of papers. We can see S. Nioka, J. S. Leigh, A. Yodh as the top 3 coauthors with the most coauthored papers with Britton Chance. 3. Discussion and Summary Note that all the above analysis and discussion are based on the 1023 records collected by ISI citation database in April, 2013. Our own collection of Brit- ton Chance's publication record, which is still an ongoing process, showed over 1500 manuscripts. We may perform additional analysis on this database once it is complete. This may provide a more com- plete picture about his research activity. Further- more, considering the tremendously diversi¯ed multi-disciplinary research conducted by Britton Chance, we can only cover some major research topics we are familiar with. The scientometric methods we used have a limited number of angles of perspectives. It is highly possible we fail to disclose many interesting or meaningful connections among the research publications by Chance and his research activities. In summary, we have presented the ¯rst scien- tometric analysis on a world preeminent scholar Britton Chance, whose research spanned multiple disciplines from physics, engineering, biology to medicine. We try to understand the pro¯les of his annual publications and citations by correlating them with his research activities. We have also summarized some key research areas that Britton Chance had focused and exerted great impact on. Among the diversi¯ed research studies Chance had conducted, metabolism and the development of physical methods to probe it appeared to be the central thread that connected all the dots. We also note that Chance had many excellent collaborators from very diversi¯ed ¯elds of science throughout his life, and that had enabled him to make such a great amount of publications with tremendous impact on science. References 1. L. Z. Li, S. Nioka, K. A. Kang, \Dedication: Britton Chance, M.D., Ph.D., D.Sc.," Adv. Exp. Med. Biol. 765, v–xiv (2013). 2. L. Leydesdor®, \Eugene Gar¯eld and algorithmic historiography: Co-words, co-authors, and journal names," Ann Library Inform. Stud. 57, 248–260 (2010). Citation analysis of the scienti¯c publications of Britton Chance 1430003-11 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . 3. B. Chance, J. Brainerd, F. Cajori, G. Millikan, \The kinetics of the enzyme-substrate compound of per- oxidase and their relation to the Michaelis theory," Science 92, 455 (1940). 4. B. Chance, \The kinteics of the enzyme-substrate compound of peroxidase," J. Biol. Chem. 151, 553– 577 (1943). 5. H. Theorell, B. Chance, \Studies on liver alcohol dehydrogenase. II. The kinetics of the compound of horse liver alcohol dehydrogenase and reduced diphosphopyridine nucleotide," Acta Chem. Scand. 5, 1127–1144 (1951). 6. B. Chance, \Rapid and sensitive spectropho- tometry. III. A double beam apparatus," Rev. Sci. Instrum. 22, 634–638 (1951). 7. B. Chance, \An intermediate compound in the catalase-hydrogen peroxide reaction," Acta Chem. Scand. 1, 236–267 (1947). 8. B. Chance, G. R. Williams, \Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization," J. Biol. Chem. 217, 383–393 (1955). 9. B. Chance, G. R. Williams, \Respiratory enzymes in oxidative phosphorylation. II. Di®erence spectra," J. Biol. Chem. 217, 395–407 (1955). 10. B. Chance, G. R. Williams, \Respiratory enzymes in oxidative phosphorylation. III. The steady state," J. Biol. Chem. 217, 409–427 (1955). 11. B. Chance, G. R. Williams, \Respiratory enzymes in oxidative phosphorylation. IV. The respiratory chain," J. Biol. Chem. 217, 429–438 (1955). 12. B. Chance, B. Hess, \Metabolic control mechanisms. IV. The e®ect of glucose upon the steady state of respiratory enzymes in the ascites cell," J. Biol. Chem. 234, 2421–2427 (1959). 13. B. Chance, B. Hess, \Metabolic control mechanisms. III. Kinetics of oxygen utilization in ascites tumor cells," J. Biol. Chem. 234, 2416–2420 (1959). 14. B. Chance, B. Hess, \Metabolic control mechanisms. II. Crossover phenomena in mitochondria of ascites tumor cells," J. Biol. Chem. 234, 2413–2415 (1959). 15. B. Chance, B. Hess, \Metabolic control mechanisms. I. Electron transfer in the mammalian cell," J. Biol. Chem. 234, 2404–2412 (1959). 16. B. Chance, D. Gar¯nkel, J. Higgins, B. Hess, \Metabolic control mechanisms. V. A solution for the equations representing interaction between gly- colysis and respiration in ascites tumor cells," J. Biol. Chem. 235, 2426–2439 (1960). 17. B. Hess, B. Chance, \Metabolic control mechanisms. VI. chemical events after glucose addition to ascites tumor cells," J. Biol. Chem. 236, 239–246 (1961). 18. B. Chance, H. Baltsche®sky, \Respiratory enzymes in oxidative phosphorylation. VII. Binding of intramitochondrial reduced pyridine nucleotide," J. Biol. Chem. 233, 736–739 (1958). 19. B. Chance, F. Jobsis, \Changes in °uorescence in a frog sartorius muscle following a twitch," Nature 184, 195–196 (1959). 20. B. Chance, B. Schoener, P. Cohen, F. Jobsis, \Localized °uorometry of oxidation-reduction states of intracellular pyridine nucleotide in brain and kidney cortex of anesthetized rat," Science 136, 325 (1962). 21. B. Chance, P. Cohen, F. Jobsis, B. Schoener, \Intracellular oxidation-reduction states in vivo," Science 137, 499–508 (1962). 22. B. Chance, B. Schoener, \Correlation of oxidation- reduction changes of intracellular reduced pyridine nucleotide and changes in electroencephalogram of the rat in anoxia," Nature 195, 956–958 (1962). 23. D. DeVault, B. Chance, \Studies of photosynthesis using a pulsed laser. I. Temperature dependence of cytochrome oxidation rate in chromatium. Evidence for tunneling," Biophys. J. 6, 825–847 (1966). 24. N. S. Scrutton, M. J. Sutcli®e, P. Leslie Dutton, \Quantum catalysis in enzymes: Beyond the tran- sition state theory paradigm. A Discussion Meeting held at the Royal Society on 14 and 15 November 2005," J. R. Soc. Interface / the R. Soc. 3, 465–469 (2006). 25. B. Chance, L. Ernster, P. B. Garland, C. P. Lee, P. A. Light, T. Ohnishi, C. I. Ragan, D. Wong, \Flavoproteins of the mitochondrial respiratory chain," Proc. Natl. Acad. Sci. USA 57, 1498–1505 (1967). 26. P. B. Garland, B. Chance, L. Ernster, C. P. Lee, D. Wong, \Flavoproteins of mitochondrial fatty acid oxidation," Proc. Natl. Acad. Sci. USA 58, 1696– 1702 (1967). 27. I. Hassinen, B. Chance, \Oxidation-reduction prop- erties of the mitochondrial °avoprotein chain," Bio- chem. Biophys. Res. Commun. 31, 895–900 (1968). 28. M. V. Gilmour, M. R. Lemberg, B. Chance, \Cytochrome oxidase and its derivatives. IX. Spec- trophotometric studies on the rapid reaction of fer- rous cytochrome c oxidase with molecular oxygen under conditions of complete and partial oxy- genation," BBA — Bioenergetics 172, 37–51 (1969). 29. B. Chance, \Cytochromes: Chemical and structural aspects," Science 159, 654–658 (1968). 30. B. Chance, C. Saronio, J. S. Leigh Jr, \Functional intermediates in the reaction of membrane bound cytochrome oxidase with oxygen," J. Biol. Chem. 250, 9226–9237 (1975). 31. B. Chance, \The energy-linked reaction of calcium with mitochondria," J. Biol. Chem. 240, 2729–2748 (1965). 32. G. Loschen, L. Floh�e, B. Chance, \Respiratory chain linked H2O2 production in pigeon heart mitochondria," FEBS Lett. 18, 261–264 (1971). L. Z. Li et al. 1430003-12 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . 33. B. Chance, S. Ele®, J. S. Leigh, Jr., \Noninvasive, nondestructive approaches to cell bioenergetics," Proc. Natl. Acad. Sci. USA 77, 7430–7434 (1980). 34. P. B. Garlick, G. K. Radda, P. J. Seeley, B. Chance, \Phosphorus NMR studies on perfused heart," Biochem. Biophy. Res. Commun. 74, 1256–1262 (1977). 35. B. Chance, G. Radda, P. J. Seeley, I. Silver, Y. Nakase, M. Bond, G. McDonald, \31P NMR of excised and in situ brain tissues," in NMR and Biochemistry: A Symposium Honoring Mildred Cohn, S. Opella & P. Lu, Eds., pp. 269–281, Marcel Dekker, Inc., New York (1979). 36. A. C. McLaughlin, H. Takeda, B. Chance, \Rapid ATP assays in perfused mouse liver by 31P NMR," Proc. Natl. Acad. Sci. USA 76, 5445–5449 (1979). 37. J. Cohen, \Scientists who fund themselves," Science 279, 178–181 (1998). 38. A. Boveris, B. Chance et al., \Enhancement of the chemiluminescence of perfused rat liver and of iso- lated mitochondria and microsomes by hydro- peroxides," Adv. Exp. Med. Biol. 2, 975–984 (1978). 39. A. Boveris, E. Cadenas, R. Reiter, M. Filipkowski, Y. Nakase, B. Chance, \Organ chemiluminescence: Noninvasive assay for oxidative radical reactions," Proc. Natl. Acad. Sci. USA 77, 347–351 (1980). 40. E. Cadenas, A. I. Varsavsky, A. Boveris, B. Chance, \Low level chemiluminescence of the cytochrome c-catalyzed decomposition of hydrogen peroxide," FEBS Lett. 113, 141–144 (1980). 41. E. Cadenas, R. P. Daniele, B. Chance, \Low level chemiluminescence of alveolar macrophages: Spec- tral evidence for singlet oxygen generation," FEBS Lett. 123, 225–228 (1981). 42. A. Greer, \Christopher Foote's discovery of the role of singlet oxygen [ 1O2 ( 1�g)] in photosensitized oxidation reactions," Acc. Chem. Res. 39, 797–804 (2006). 43. M. J. Thomas, P. S. Shirley, C. C. Hedrick, L. R. DeChatelet, \Role of free radical processes in stimulated human polymorphonuclear leukocytes", Biochemistry 25, 8042–8048 (1986). 44. L. Powers, W. E. Blumberg, B. Chance, C. H. Barlow, J. Leigh, J. S., J. Smith, T. Yonetani, S. Vik, \Structure and function of copper atoms in cytochrome oxidase," Adv. Exp. Med. Biol. 2, 863– 871 (1978). 45. L. Powers, W. E. Blumberg, B. Chance, C. H. Barlow, J. S. Leigh, Jr., J. Smith, T. Yonetani, S. Vik, J. Peisach, \The nature of the copper atoms of cytochrome c oxidase as studied by optical and x-ray absorption edge spectroscopy," Biochim. Biophys. Acta 546, 520–538 (1979). 46. J. Peisach, L. Powers, W. E. Blumberg, B. Chance, \Stellacyanin. Studies of the metal-binding site using x-ray absorption spectroscopy," Biophys. J. 38, 277–285 (1982). 47. B. Chance, R. Fischetti, L. Powers, \Structure and kinetics of the photoproduct of carboxymyoglobin at low temperatures: An X-ray absorption study," Biochemistry 22, 3820–3829 (1983). 48. L. Garcia-Iniguez, L. Powers, B. Chance, S. Sellin, B. Mannervik, A. S. Mildvan, \X-ray absorption studies of the Zn 2þ site of glyoxalase I," Biochem- istry 23, 685–689 (1984). 49. B. Chance, J. S. Leigh, H. Miyake, D. S. Smith, S. Nioka, R. Greenfeld, M. Finander, K. Kaufmann, W. Levy, M. Young, \Comparison of time-resolved and -unresolved measurements of deoxyhemoglobin in brain," Proc. Natl. Acad. Sci. USA 85, 4971–4975 (1988). 50. B. Chance, S. Nioka, J. Kent, K. McCully, M. Fountain, R. Greenfeld, G. Holtom, \Time-resolved spectroscopy of hemoglobin and myoglobin in rest- ing and ischemic muscle," Anal. Biochem. 174, 698– 707 (1988). 51. M. S. Patterson, B. Chance, B. C. Wilson, \Time resolved re°ectance and transmittance for the non- invasive measurement of tissue optical properties," Appl. Opt. 28, 2331–2336 (1989). 52. M. A. O'Leary, D. A. Boas, B. Chance, A. G. Yodh, \Refraction of di®use photon density waves," Phys. Rev. Lett. 69, 2658–2661 (1992). 53. D. A. Boas, M. A. O'Leary, B. Chance, A. G. Yodh, \Scattering of di®use photon density waves by spherical inhomogeneities within turbid media: Analytic solution and applications," Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994). 54. X. Li, B. Beauvoit, R. White, S. Nioka, B. Chance, A. G. Yodh, Optical Tomography, Photon Mi- gration, and Spectroscopy of Tissue and Model Media: Theory, Human Studies, and Instrumenta- tion Tumor Localization Using Fluorescence of Indocyanine Green(ICG) in Rat Models, Vol. 789 SPIE, San Jose, CA, USA (1995). 55. A. Yodh, B. Chance, \Spectroscopy and imaging with di®using light," Phys. Today 48, 34–40 (1995). 56. X. D. Li, T. Durduran, A. G. Yodh, B. Chance, D. N. Pattanayak, \Di®raction tomography for bio- chemical imaging with di®use-photon density waves," Opt. Lett. 22, 573–575 (1997). 57. V. Ntziachristos, X. Ma, A. G. Yodh, B. Chance, OSA Trends in Optics and Photonics, E. M. Sevick- Muraca, J. A. Izatt, M. N. Ediger, Eds., Quanti- tation of Functional Motor Cortex Activity using Time-Resolved Spatially Localized NIR Spec- troscopy, pp. 200–204, Optical Society of America, Washington, DC (1998). 58. V. Ntziachristos, A. G. Yodh, M. D. Schnall, B. Chance, \MRI-guided di®use optical spectroscopy Citation analysis of the scienti¯c publications of Britton Chance 1430003-13 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . of malignant and benign breast lesions," Neoplasia 4, 347–354 (2002). 59. G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, 3rd, A. G. Yodh, \Time-dependent blood °ow and oxygenation in human skeletal muscles measured with noninvasive near-infrared di®use optical spectroscopies," J. Biomed. Opt. 10, 024027 (2005). 60. X. Intes, B. Chance, M. J. Holboke, A. G. Yodh, \Interfering di®usive photon-density waves with an absorbing-°uorescent inhomogeneity," Opt. Express 8, 223–231 (2001). 61. A. Villringer, B. Chance, \Non-invasive optical spectroscopy and imaging of human brain function," Trends Neurosci. 20, 435–442 (1997). 62. D. M. Mancini, L. Bolinger, H. Li, K. Kendrick, B. Chance, J. R. Wilson, \Validation of near-infrared spectroscopy in humans," J. Appl. Physiol. 77, 2740–2747 (1994). 63. E. M. Sevick, B. Chance, J. Leigh, S. Nioka, M. Maris, \Quantitation of time- and frequency-resolved opti- cal spectra for the determination of tissue oxy- genation," Anal. Biochem. 195, 330–351 (1991). 64. V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, \Concurrent MRI and di®use optical tom- ography of breast after indocyanine green enhancement," Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000). 65. G. Zheng, H. Li, K. Yang, D. Blessington, K. Licha, S. Lund-Katz, B. Chance, J. D. Glickson, \Tricarbocyanine cholesteryl laurates labeled LDL: New near infrared °uorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia," Bioorg. Med. Chem. Lett. 12, 1485–1488 (2002). 66. M. Zhang, Z. Zhang, D. Blessington, H. Li, T. M. Busch, V. Madrak, J. Miles, B. Chance, J. D. Glickson, G. Zheng, \Pyropheophorbide 2-deox- yglucosamide: A new photosensitizer targeting glu- cose transporters," Bioconjug. Chem. 14, 709–714 (2003). 67. J. Chen, K. Ste®lova, M. J. Niedre, B. C. Wilson, B. Chance, J. D. Glickson, G. Zheng, \Protease-trig- gered photosensitizing beacon based on singlet oxygen quenching and activation," J. Am. Chem. Soc. 126, 11450–11451 (2004). 68. Z. Zhang, D. Blessington, H. Li, T. M. Busch, J. Glickson, Q. Luo, B. Chance, G. Zheng, \Redox ratio of mitochondria as an indicator for the re- sponse of photodynamic therapy," J. Biomed. Opt. 9, 772–778 (2004). 69. Z. Zhang, H. Li, Q. Liu, L. Zhou, M. Zhang, Q. Luo, J. Glickson, B. Chance, G. Zheng, \Metabolic imaging of tumors using intrinsic and extrinsic °u- orescent markers," Biosens. Bioelectron. 20, 643– 650 (2004). 70. L. Z. Li, R. Zhou, H. N. Xu, L. Moon, T. Zhong, E. J. Kim, H. Qiao, R. Reddy, D. Leeper, B. Chance, J. D. Glickson, \Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential," Proc. Natl. Acad. Sci. USA 106, 6608– 6613 (2009). 71. L. Z. J. Li, R. Zhou, T. Zhong, L. Moon, E. J. Kim, H. Qiao, S. Pickup, M. J. Hendrix, D. Leeper, B. Chance, J. D. Glickson, \Predicting melanoma metastatic potential by optical and magnetic res- onance imaging," Adv. Exp. Med. Biol. 599, 67–78 (2007). 72. H. N. Xu, S. Nioka, J. D. Glickson, B. Chance, L. Z. Li, \Quantitative mitochondrial redox imaging of breast cancer metastatic potential," J. Biomed. Opt. 15, 036010 (2010). 73. H. N. Xu, J. Tchou, B. Chance, L. Z. Li, \Imaging the redox states of human breast cancer core biopsies," Adv. Exp. Med. Biol. 765, 343–349 (2013). 74. H. N. Xu, R. C. Addis, D. F. Goings, S. Nioka, B. Chance, J. D. Gearhart, L. Z. Li, \Imaging redox state heterogeneity within individual embryonic stem cell colonies," J. Innov. Opt. Health Sci. 4, 279–288 (2011). 75. J.-R. Horng, S. Nioka, A. Quo, B. Chance, \A novel time-shared °uorometer gives the mitochondrial redox state as the ratio of two components of the respiratory chain of the animal and human buccal cavity with quantitative measures of the redox energy state," J. Innov. Opt. Health Sci. 3, 235–245 (2010). 76. B. Chance, H. Sies, A. Boveris, \Hydroperoxide metabolism in mammalian organs," Physiol. Rev. 59, 527–605 (1979). 77. A. Boveris, B. Chance, \The mitochondrial gener- ation of hydrogen peroxide. General properties and e®ect of hyperbaric oxygen," Biochem. J. 134, 707– 716 (1973). 78. B. Chance, G. R. Williams, \The respiratory chain and oxidative phosphorylation," Adv. Enzymol. Relat. Subj. Biochem. 17, 65–134 (1956). 79. B. Chance, A. C. Maehly, \Assay of catalases and peroxidases," Methods Enzymol. 2, 764–775 (1955). 80. B. Chance, \Spectra and reaction kinetics of res- piratory pigments of homogenized and intact cells," Nature 169, 215–221 (1952). 81. B. Chance, \Spectrophotometry of intracellular res- piratory pigments," Science 120, 767–775 (1954). L. Z. Li et al. 1430003-14 J. I nn ov . O pt . H ea lt h S ci . 2 01 4. 07 . D ow nl oa de d fr om w w w .w or ld sc ie nt if ic .c om by U N IV E R S IT Y O F A M S T E R D A M o n 12 /1 6/ 14 . F or p er so na l us e on ly . Citation analysis of the scientific publications of Britton Chance in ISI citation indexes 1. Introduction to Britton Chance 2. Scientometric Analysis 3. Discussion and Summary References