cord-002895-z82e7z2v	2018	Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The comparative transcriptional profile of SPF White Leghorn chicken embryos (one control and one infected at 18 days, harvested 72 hpi) was determined using the Chicken Innate and Adaptive Immune Responses RT 2 Profiler Array (QIAGEN Inc., Germantown, MD, United States) as an initial screen to select for immune genes in the embryo that are differentially expressed during infection since studies have not been performed previously.
cord-003444-dmpoy0b1	2019	
cord-003898-y6zpvw84	2019	title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications The aim of this study was to utilize RNA sequencing (RNAseq) technology to not only reveal the hNEC responses (from multiple individuals) against influenza infection, but also to identify those genes with high magnitude changes to serve as potential reference markers of the innate responses of influenza infection. After deriving the transcriptomes by RNAseq, we then further investigated whether the changes in expression of genes resulted in alterations in secretory cytokines and chemokines early in the infection of hNECs. Initially, we detected significant reductions in multiple cytokines at 8 hpi, with the exception of IL-15 which was increased ( Figure S2 ). In conclusion, RNAseq technology allowed us to accurately quantify the magnitude of gene expression changes, as well as the relevant enriched pathways during H3N2 influenza virus infection of hNECs, which can serve as a baseline for future clinical studies.
cord-004518-jd1wxobz	2007	
cord-005607-b1a39hhw	2000	Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation.¶The body relies on the inflammatory response for protection. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage.¶It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. Endothelial cells, mesothelial cells, fibroblasts and epithelial cells are also all involved not only with their capacity to drive the inflammatory response through mediator generation but also in innate immune defences including through the production of antimicrobial proteins.
cord-007375-hqmyund4	2007	
cord-009836-7o6htufh	2006	
cord-015021-pol2qm74	1994	It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events.
cord-015147-h0o0yqv8	2014	Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis.
cord-015910-d9gxew91	2005	Binding of the transcription factors is implicated in activation of a wide range of genes associated with inflammation and the immune response, including those encoding cytokines, cytokine receptors, cell adhesion molecules, acute-phase proteins, and growth factors (Schreck, Rieber, & Baeurerle, 1991) (Fig. 4 ) . While inflammation may be exerting deleterious effects most obviously in patients, people on the borderline of health and disease living in the general population Table 4 Nutrients Commonly Used in Immunonutrient Supplements and Their Potential Mode of Action • n-3 polyunsaturated fatty acids: act as anti-inflammatory agents and reverse immunosuppression • Sulfur amino acids and their precursors: enhance antioxidant status via GSH synthesis • Glutamine: nutrient for immune cells, improves gut barrier function, precursor for GSH • Arginine: stimulates nitric oxide and growth hormone production, improves helper T-cell numbers • Nucleotides: RNA and DNA precursors, improve T-cell function may also require nutritional modulation of ongoing inflammatory processes.
cord-016713-pw4f8asc	2013	The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al.
cord-017817-ztp7w9yh	2018	Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] .
cord-017838-fbotc479	2010	Thus, electroporation-mediated DNA vaccination represents a promising new strategy for the elicitation of strong immune responses directed against the expressed antigen(s) and not the vector, and ongoing studies are currently underway to optimize the working parameters of this technique. [26] demonstrated in mice that upon electroporative treatment, the delivery of a weakly immunogenic hepatitis B virus (HBV) surface antigen (Hbs Ag) DNA vaccine resulted in an increased humoral immune response, characterized by rapid onset and higher titers of anti-Hbs Ag antibodies. In addition, the authors observed in the same study that the potency of an HIV gag pDNA vaccine was increased as shown by the lower dosage of DNA required to induce higher antigen-specific antibody levels and increased CD8 + T cell responses. [31] have demonstrated that gene electrotransfer efficiently increased the cellular immune response both in mice and rhesus macaques vaccinated with a plasmid encoding a nonstructural region of hepatitis C virus (HCV).
cord-018254-v8syiwie	2012	This act authorized more than 1.5 billion US dollars in grants to state and local governments and healthcare facilities to improve planning, training, detection, and response capacity as well as funding to expand the federal Strategic National Stockpile of medications and vaccines and upgrade food inspection capacity and CDC facilities that deal with public health threats. In addition to the central role the LRN played in detecting and responding to the 2001 anthrax letter event, the commitment to infrastructure support and standardized platform testing capacity within the LRN has also proven extremely bene fi cial in assisting with more rapid and broader deployment of tests developed in response to other emerging public health threats such as the 2003 Severe Acute Respiratory Syndrome (SARS) and the 2009 H1N1 avian in fl uenza pandemic.
cord-018265-twp33bb6	2007	
cord-018475-h8qwxdtn	2007	With the erosion of strict borders between countries (particularly in the European Union) and even world regions (since the fall of the Soviet bloc), the advance and portability of high-tech weaponry including biological, chemical, and nuclear hazards, and the ease and speed of communication through the Internet and telephones for purposes of recruitment, training, and planning terror attacks -terrorists now have a global playing field in which even small groups of individuals can motivate, plan, and enact mass terrorist events. Governments and media must work together preparing ahead of time on how to communicate calmly in such crises in a manner that will offer useful preventative measures, minimize the potential negative effects of psychosocial contagions (including citizenry becoming noncompliant and aggressive), prevent mass sociogenic illness from occurring, and prevent overwhelming of the medical systems by those whose emotional state has put them in need of medical care.
cord-018839-yfaji9cv	2017	
cord-018937-5yo4rfml	2015	Disaster is defi ned as any event that causes "a serious disruption of the functioning of a community or a society involving widespread human, material, economic or environmental losses and impacts, which exceeds the ability of the affected community or society to cope using its own resources" [ 1 ] . The Incident Command System (ICS) provides a structure to enable agencies with different legal, jurisdictional, and functional responsibilities to coordinate, plan, and interact effectively on scene [ 11 ] . During a disaster, it is extremely important to establish a unifi ed command, because it enables all responsible agencies to manage and coordinate an incident together by establishing a common approach and a single IAP. It is defi ned as second incident caused by the terrorists, following the fi rst event, with the goal of striking the fi rst responders that are on scene.
cord-021175-0ikkl3hk	2018	
cord-021424-kocwsyi7	2009	This activation process includes widespread changes in the gene expression profi le of the cells with hundreds of genes being either switched on or off in response to signals generated from the pathogen-detecting TLRs. The response of individual genes has been studied in minute detail for a handful of genes and while this has produced an understanding of some aspects of host response to infection it by no means gives us the total picture. Studies in both animal models and human populations have shown that infectious disease and the response of the host to a specifi c infection also has a complex genetic component ( Clementi and Di Gianantonio, 2006 ; Lipoldova and Demant, 2006 ; Marquet et al., 1996 ; Mira et al., 2004 ) . Expression profi ling studies have been used to investigate the differences in the host response to pathogenic and nonpathogenic strains of specifi c infectious agents.
cord-021966-5m21bsrw	2009	Because a number of proteins produced in isolation by recombinant methods have been observed to elicit lower immune responses than do natural infections or live attenuated vaccines, the development and use of adjuvants to optimize recombinant vaccine immunogenicity represent an important parallel area for future exploration. Modern molecular biology and biochemistry have provided numerous options for vaccine immunogen presentation, including recombinant proteins (and recombinant virus-like particles (VLPs)), synthetic proteins, protein-polysaccharide conjugates, and gene delivery systems (recombinant viral vectors, or DNA vaccines) >> Is the antigen of interest sufficiently immunogenic on its own, or is augmentation of the desired immune response by conjugation to a specific carrier or addition of an adjuvant necessary to elicit a sufficient and sufficiently durable immune response in individuals in the target population for vaccination?
cord-021980-ddau5fu3	2015	
cord-022076-zpn2h9mt	2009	
cord-022252-9yiuuye3	2013	A few viruses are remarkable because they cause no pathological changes at all in the cell, even during a productive infection in which infectious virus particles are produced. Primary consideration will be given to those substances which are produced under ecologically significant conditions (i.e. in the natural host or relevant animal model) and cause (also in biologically relevant systems) damage to cells or tissues thereby contributing to disease. Here we consider toxins which act on extracellular substances and are responsible for many of the main features of the diseases caused by the infecting organism. Circulating immune complexes are also deposited in the walls of small blood vessels in the skin and elsewhere, where they may induce inflammatory changes.* The prodromal rashes seen in exanthematous virus infections and in hepatitis B are probably caused in this way.
cord-022435-pztn9075	2009	Domestically, the Department of Family and Community Services (FaCS) coordinated government policy and delivery of assistance to Australians and their families affected by the crisis. A clear lesson from Bali was the extent to which overseas events can resonate at the local community level, underlining the importance of domestic and state/territory agencies being activated early in response to a major overseas crisis. • clarify the roles of agencies and non-government organisations in crisis responses; • review links between Australian government and state disaster plans; and • identify and rectify any gaps in interagency coordination arrangements. One of the lessons of the Australian Government''s FMD simulation, Exercise Minotaur (see http://www.affa.gov.au/exerciseminotaur), was the need for agencies to look at human resource capacity in a number of key areas, particularly that of skilled and trained technical employees.
cord-022592-g7rmzsv5	2016	14, 15, [27] [28] [29] [30] [31] [32] [33] Prematurity, low birth weight (especially infants weighing less than 1,000 g), male sex, a maternal vaginal culture positive for group B streptococcus (GBS), prolonged rupture of membranes, maternal intrapartum fever, and chorioamnionitis are strongly associated with an increased risk for early-onset sepsis. In addition to the initial inflammatory response including complement activation, molecular detection of PAMPs promotes IL-1β and IL-6 production, which in turn increases the production of multiple other innate proteins that possess valuable immune function and serve to reduce pathogen load. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network
cord-022888-dnsdg04n	2009	Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery.
cord-023055-ntbvmssh	2004	Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures.
cord-023143-fcno330z	2004	Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells.
cord-023935-o2ffxgnn	2011	SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response.
cord-024571-vlklgd3x	2019	
cord-026949-nu46ok9w	2020	
cord-026960-g844u7xg	2020	To address this limitation, this paper proposes an adaptive response matching network (ARM) to better model the matching relationship in multi-turn conversations. Specifically, the Dual-encoder model [8] used two LSTMs to generate the embeddings for the utterances and candidate response respectively to compute the matching score. Deep attention model (DAM) [20] proposed self-attention and cross-attention to construct semantic representations at different granularity, and the multirepresentation fusion network (MRFN) [13] has further applied multiple representation strategies for utterances and fused them in the final step to compute the matching scores. Few of them studied how to adapt the matching model to different types of utterances and how to incorporate the domain knowledge in a more general way, which is the focus of our paper. Although a few models have been proposed to solve the problem of multi-turn response selection [2, 13, 17, 20] , none of them studied how to directly adapt the matching mechanisms to different utterance types.
cord-029598-qwpya4ox	2020	The task force used its collective expertise to develop four key mitigation strategies, described in detail below, to reinforce staff wellness throughout the crisis: Wellness Rounds, a Wellness Consult Service, an advanced mental health intervention program known as Wellness Plus, and a central Wellness Resource Hub with Wellness Rooms on frontline floors. We established a consult service (Figure 1 ) where any clinical unit or individual can connect directly with a member of the Wellness Response Team for evaluation, triage, and recommendations to improve mental health and well-being. When triggered, the individual is escorted to one of the unit-level Wellness Rooms or the central Wellness Resource Hub (see below) where an experienced clinician (typically a physician or other prescriber) completes a thorough mental health assessment, including identifying an immediate therapeutic intervention and appropriate followup.
cord-030999-27wennun	2020	
cord-031081-szqrjxq2	2020	In conjunction with these articles, we hope that this conceptual framework will provide a point of departure for researchers seeking to enhance the understanding of how consumers and markets collectively respond over the short term and long term to threats that disrupt consumers'' routines, lives, or even the fabric of society. Our goal is not to provide a comprehensive review of existing literature, but rather a guide to researchers seeking to increase our collective understanding of how consumers and markets together respond over short and long durations to threats that disrupt their very being. The findings of this article suggest that economic recessions, pandemics, and terror threats can affect subjective life expectancy for some consumers, leading to different financial and health decisions than they might make otherwise, as well as potentially impacting their mental health.
cord-031885-by4cujyy	2020	
cord-032600-lldbjm77	2020	2 Second-generation efforts employed more characterized materials, such as the biodegradable synthetic polymer poly (D,L-lactic-co-glycolic acid) (PLGA), which is a widely investigated nanoparticle adjuvant for controlled and effective delivery of vaccine antigens, including synthetic peptides. 32 Thus, pathogen-mimicking nanoparticles can be engineered to enhance the immune response by controlling when and where vaccine components are delivered intracellularly to APCs. 15 A plethora of particulate delivery systems for immunoengineering have been developed, which are summarized further in this review. Recently, we have combined such engineering and rational vaccine design approaches to develop a nanoparticle-based adjuvant and antigen-delivery system designed to be active in human newborns and infants. Furthermore, such formulations hold substantial potential for early life immunization by serving as a dual antigen/adjuvant delivery system that mimics the enhanced neonatal innate and adaptive immune responses elicited by the live Bacille Calmette-Guerin (BCG) vaccine.
cord-033714-rz5unqaz	2020	The visualization of informal settlements in many COVID-19 discussions, however, is of homogenous highdensity inner-city shacks, with insufficient attention given to lowerdensity settlements (more likely to have urban agriculture) that may also face health and economic emergencies. (46) The wealth of grassroots responses to COVID-19 is elaborated by the International Institute for Environment and Development (IIED), which has drawn on experiences from across its partners in the global South, who provide evidence of local groups stepping in to reduce health risks and provide emergency access to food and hygiene. Meanwhile, the vast majority of urban poor communities (85%) reported government-provided "palliatives" intended for the vulnerable had not reached them." (68) Similar findings are evident in Brazil where, for example, low-income favela residents in São Paulo are not receiving the monthly emergency basic income payment (worth US$ 115), despite the shutdown by the city authorities of informal trading on 15 April 2020. Local response in health emergencies: key considerations for addressing the COVID-19 pandemic in informal urban settlements
cord-126015-zc7u3g34	2020	To better understand what impact these genetic variants in immune response genes may have in the differences observed in the immune response to SARS-CoV-2, a quantitative analysis of a dynamical systems model that considers both, the magnitude of viral growth, and the subsequent innate and adaptive response required to achieve control of infection is considered. To better understand what impact these genetic variants in immune response genes may have in the differences observed in the immune response to SARS-CoV-2, a quantitative analysis of a dynamical systems model that considers both, the magnitude of viral growth, and the subsequent innate and adaptive response required to achieve control of infection is considered. The HLA genes exhibit extreme allelic polymorphisms and present viral peptides on host HLA molecules to T cells to trigger an adaptive immune response. A quantitative approach relating differences in cytokine levels and polymorphisms in the immune response pathways may help identify patients at risk of severe disease.
cord-216972-migs9rxb	2020	Through a forced choice lab study task (n=19) and in the wild deployment (n=18) of a notificationdialog experiment on smartphones, we show that people become more accurate and faster at option selection as they develop an interface habit. The contribution of the current paper comes from providing quantitative evidence of how the process of forming and disrupting habits affects user performance in a forced choice interaction task, similar to those seen in notification dialogs or alert boxes. The current research contributes key insight on fundamental user behaviours by quantifying how the process of habit formation and disruption through design affect the speed and accuracy of interactions. The experimental evidence of study 1 shows that, like other habits, allowing participants to form interface habits leads to significant gains in performance, as users became both more accurate and quicker at selecting the desired option.
cord-252568-b8sbvy0g	2017	There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. However, many NPs have been shown to stimulate immune responses, including cell recruitment, activation of antigen (Ag)-presenting cells (APCs), and induction of cytokine and chemokine release. Among the vaccines targeting extracellular bacteria and toxin, two were formulated with lipopolysaccharide (LPS) in glycopeptide Ag. The use of glycoantigen and LPS can trigger an intense response through TLR4 and B cell receptor activation; the presence of gold NPs (AuNPs) may have minimal influence on this response. To understand the possible uses of MeNPs as platforms for vaccines against infectious diseases, analysis is needed of the impact of different physicochemical characteristics of NPs on the innate immune response (Figure 1) .
cord-255725-7l9lk9x2	2011	
cord-257027-q2y7fewk	2011	Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. The publication of the Haemophilus influenzae genome, the first pathogen to have its complete genome sequence published as a result of an approach to genome analysis using new technologies of high-throughput sequencing (5) , has opened the mind of scientists to a range of new possible approaches to the study of microorganisms and has marked the beginning of a new era in vaccine development: the identification of pathogen candidate antigens based on the knowledge of the genome of the pathogen and on the understanding of microbial biology and host-pathogen interactions, an approach called reverse vaccinology (6) .
cord-257167-rz4r5sj7	2006	SY1-3-11-3 SAD: A novel kinase implicated in phosphoproteome at the presynaptic active zone Toshihisa Ohtsuka Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama, Japan SAD is a serine/threonine kianse, which has been shown to regulate various neuronal functions during development, including clustering synaptic vesicles, maturation of synapses, and axon/dendrite polarization: these have recently been revealed by genetic studies in C. The results suggest that EAAT4 plays a major role in regulating the concentration of CF transmitters, possibly glutamate, in the route of its extrasynaptic diffusion, and determining the degree of CF-induced inhibition of GABA release from BCs depending on the regional difference of EAAT4 expression in postsynaptic PCs. Chitoshi Takayama 1 , Yoshiro Inoue 1 1 Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo, Japan GABA mediates inhibitory transmission in the adult central nervous system (CNS).
cord-257722-7rmzaau4	2019	
cord-263315-g7os15m1	2018	
cord-264159-e9071tyv	2020	
cord-266204-ipa017wz	2018	
cord-266750-41gth6o0	2020	A better understanding of this relationship can inform the development of evidencebased management strategies in these patients and limit admissions to overcrowded ICUs. To demonstrate and further define these developing theories on the coagulative and inflammatory risks associated with the surgical treatment of trauma patients with COVID-19, we will present an unexpected outcome on such a patient at our institution. In addition, the hypercoagulable state secondary to COVID-19 and the inflammatory load of intramedullary reaming, fat emboli, and pulmonary embolism resulted in a "second hit" that may have cumulatively pushed our patient past a "tipping point" and into respiratory failure (Fig. 4) . The level of cytokine response, hypercoagulability, and pulmonary dysfunction associated with the COVID-19 virus may predispose to a catastrophic "second hit" after even low-energy trauma. Careful consideration and risk/benefit analysis, including preoperative evaluation of systemic inflammation and respiratory status, is paramount in patients with COVID-19 presenting with orthopaedic trauma injuries.
cord-269943-g77qe5ml	2020	
cord-270469-lle32mha	2012	
cord-271250-ywb26cq6	2019	In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. Intact MyD88 signaling in each of the three types of APCs (DCs, macrophages and B cells) is essential for robust activity of TLR ligand-based vaccine adjuvants (PorB, a TLR2 ligand and CpG, a TLR9 ligand) such as induction of in vivo cytokine responses, germinal center (GC) formation and antibody production [49] . A combination adjuvant consisting of poly(I:C), a host defense peptide and PCEP when delivered intranasally transiently induces production of chemokines and cytokines in murine respiratory tissues, which promotes infiltration and activation of DCs, macrophages, and neutrophils to generate improved mucosal and systemic immune responses [55] .
cord-272512-gevrlcvy	2009	
cord-273479-kira7mz6	2004	
cord-274027-ovdhnajp	2020	
cord-276628-uxsjyezo	2019	TCR stimulation leads to a variety of functional responses, such as cytolysis, cytokine production, regulatory effects, and even phagocytosis and antigen presentation, that depend on the activation of receptors and coreceptors. γδ T cells also express various cytokine receptors that contribute to their activation (IL-2R, IL-15R, IL-23R, etc.) and-fine tune their functional responses. SLC11A1 is a divalent metal transporter that is thought to be expressed only in myeloid and macrophage cells; it is important in effective responses against intracellular bacterial infections [49À51]. Follow-up functional assays examined their cell type specificity, induced cytokine responses, and benefit in various infectious disease models [110, 112] . Yamoa polysaccharides activate γδ T as well other immune cells, such as monocytes, and, when given in vivo, enhance protection from infection [110] . Porcine γδ T cells: possible roles on the innate and adaptive immune responses following virus infection
cord-278397-u33x4jaw	2018	Recent efforts have focused on identifying relevant immune surveillance sensors and components of downstream signaling-Toll-like receptors (TLRs) and their cognate ligands, cytosolic sensing of RNA (primary mediated by the RIG-I/IPS-1 axis), cytosolic sensing of DNA (primary mediated by the cGAS/STING axis), and the inflammasome pathway (primary mediated by NOD-like receptors; NLRs) (Broz and Monack, 2013; Kieser and Kagan, 2017; Kumar et al., 2011a ). It has also been suggested that chronic cGAS/STING activation induced by self DNA may be responsible for induction of aberrant inflammatory diseases like systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and polyarthritis (Barber, 2015; Crowl et al., 2017) . Use of DNA damage induced agents like 7,12-dimethylbenz-α-anthracene (DMBA) has helped shed light on the underlying events initiate the DNA damage-induced immune response via cytosolic DNA sensing pathway and implicates nucleosome leakage in eliciting cGAS/STING-dependent signal activation via recognition of self-DNA (Barber, 2015) .
cord-278938-bmahwxbn	2020	
cord-280605-2i4gk7et	2020	
cord-281437-cb3u1s7s	2019	
cord-281883-l9yshyc7	2009	
cord-284845-on97zu6w	2016	Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. As emerging viral infections often result in severe illness including respiratory failure [severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza] and multiorgan failure [Ebola virus disease (EVD)], understanding complex pathogenesis of these infections is required for effective vaccine and therapeutic design and for improved patient care. Specifically, detailed natural history studies merging multiple data streams including OMICS approaches (high-throughput gene expression and kinomics) and focused translational investigations utilizing relevant models that can be validated to human disease are needed to clarify disease pathogenesis, advance therapeutic discovery, and facilitate regulatory approval.
cord-285778-80baxwgc	2014	Some innate mechanisms require no induction and are completely non-specific, whereas others are inducible and involve broad receptor-mediated recognition of a limited number of pathogen-associated or damage-associated molecular patterns (PAMPs/DAMPs). When invaders breach anatomical and physiological barriers, innate leukocytes start to take action as a result of pattern recognition mediated by the binding of PRMs to PAMPs furnished by pathogens and to DAMPs emanating from damaged host cells. If the pathogen manages to enter the underlying cell layer, mechanisms mediated by complement and innate leukocytes are induced due to relatively broad recognition of PAMPs. If a more targeted, pathogen-specific response becomes necessary, elements of innate immunity then facilitate induction of highly specific adaptive responses initiated by engagement of the antigen receptors of B, Th or Tc lymphocytes. Innate leukocytes activated by the binding of PRRs to PAMPs provided by the attacking pathogen, or to DAMPs present due to host cell injury or death, work quickly to eliminate the invader using the mechanisms of inflammation, phagocytosis and target cell lysis.
cord-285982-1a5u7uux	2009	The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Development in this area has greatly advanced over the years and human clinical trials of DNA vaccines have now been conducted against various infectious pathogens including the malaria parasite, dengue viruses, cytomegalovirus (CMV), Ebola virus, seasonal influenza viruses, avian or pandemic influenza viruses, West Nile virus (WMV), SARS coronavirus, hepatitis B virus, and HIV. Because the process of antigen production by host cells after DNA vaccination mimics the production of antigens during a natural infection, the resulting immune response is thought to be similar to the type induced by pathogens. Lastly, the first human clinical trial of a DNA vaccine formulated with Vaxfectin ® has been completed with plasmids that encode pandemic influenza virus antigens (H5N1).
cord-286072-kgpvdb42	2020	
cord-287396-18p171nr	2014	Other meta-analysis studies, examining the immune response to Salmonella typhimurium, combine microarray information with data such as serum cytokine measurements or microbiota differences. typhimurium will be discussed in the section ''''Overall value of transcriptomics in important infectious swine diseases.'''' In addition, whole genome microarrays were used to study pig response to Haemophilus parasuis infection by Zhao et al. In 2010, Xiao and collaborators performed a 3'' tag digital gene expression (DGE) analysis of the porcine lung transcriptome on pigs infected with the PRRS virus (Xiao et al. Most pig immune studies conducted to identify host response to common porcine pathogens or to immune response stimulators such as LPS or PMA/ionomycin described in this review provide gene expression data from a single tissue or isolated cell type, and this at a limited number of times post-infection/stimulation. Recently, such a meta-analysis was performed by combining results of several microarray-based pig immune studies to find PRRS-specific responses (Badaoui et al.
cord-288868-qfdxri93	2005	Thus, the use of reverse genetics enables rapid production of a reference vaccine virus in response to the emergence of a new influenza variant [15 ,16] . Activation of DCs increases their ability to process and present antigen and to attract and activate T cells through cytokine secretion; consequently, several cytokines are 414 Host-pathogen interactions Table 1 Human TLR agonists used as adjuvants in vaccine formulations in clinical trials or licensed vaccines a . When viral vehicles (vaccinia or adenovirus) were compared with loaded DCs in terms of their ability to overcome established tolerance and induce immune responses in a transgenic mouse model, the viral formulations were able to do so, whereas DCs required repeated administration of TLR agonists or irrelevant virus, or removal of suppressive CD4 + CD25 + Treg cells [54 ] . A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease
cord-289961-7q2wkwrf	2017	Exploiting the same transport mechanisms aimed at detaining viruses, nanoparticle vaccines can effectively target immune cells in lymph nodes, delivering antigens or adjuvants following administration in peripheral tissues [13, 141, 142] (Fig. 3A) . Given the privilege of nanocarriers in lymphatic transport, nanoparticles have been shown to enhance the delivery of target antigens to lymph nodes and resident immune cells for processing and immune activation. In their animal study, strong anti-ovalbumin humoral response was observed [13] , highlighting the benefit of nanoparticle-mediated lymph node delivery on enhancing antigen processing. These virus-like particles showed high immunogenicity in both murine and avian models and enhanced anti-viral IgA and IgG titers and cellular immune responses in comparison to free protein antigens and a commercial WIV vaccine [155] . Not only can nanoparticle vaccines enhance humoral responses against target antigens, they have been shown to promote cell-based immunity as well as immunological memory.
cord-290264-pv7ijdnx	2020	1 This piece will dig deeper into biodefense policy as well as suggest specific actions that the data science community can take to contribute to COVID-19 resilience, response, and recovery efforts. Starting at the top and looking more deeply into risk and resilience in the United States, much of the policy stems from the Homeland Security Presidential Directive 21, which outlines the policy and strategy for public health and medical preparedness. This outbreak is past the point of prevention, and the response must now focus on minimizing the effects as people get sick. A toolset that I have personally used over the years for rapid development and deployment is CommCare by Dimagi, and they have already built a toolkit and guide specifically for COVID-19 outbreak response. 8 My last trip during that outbreak focused upon rebuilding local infrastructure to enable the local health systems to get back to full operation, including the possibility of an Ebola-infected patient presenting and seeking care.
cord-292983-msuluuuu	2020	In particular, self-amplifying RNA (saRNA) derived from alphavirus expression vectors has shown to be very efficient to induce humoral and cellular responses against many antigens in preclinical models, being superior to non-replicating mRNA and DNA. In particular, self-amplifying RNA (saRNA) derived from alphavirus expression vectors has shown to be very efficient to induce humoral and cellular responses against many antigens in preclinical models, being superior to non-replicating mRNA and DNA. This type of LNP-delivered saRNA vaccines, named SAM (for self-amplifying mRNA) platform, have shown great potential to generate immune responses against influenza virus [20] [21] [22] and Toxoplasma gondii [23] . Despite the fact that the ta-RNA system was able to induce good immune responses in vivo against influenza virus HA, it did not outperform vaccination with a single saRNA molecule expressing the same antigen.
cord-293893-ibca88xu	2020	
cord-296886-0bma2749	2014	
cord-297776-k38jssr0	2020	gene expression, we report significant transcriptional upregulation of multiple genes associated with activation of ER sensors IRE1, ATF6, and PERK, such as Edem1, Hspa5 (encoding BiP protein), and Ddit3 (encoding CHOP), in response to virus replication, with the most robust response detected in cells infected with the wild-type or DUBmut virus infection (Fig. 5B, C, and D) . Overall, these differential gene expression analyses in macrophages reveal similar host responses to the wild-type and DUBmut viruses that include activation of UPR pathways and proinflammatory genes, whereas a distinct transcriptional profile during infection with the EndoUmut virus is predominately defined by a focused, robust antiviral response. The results presented here, and from studies of the MERS-CoV dORF3-5 mutant virus (26) Upon infection of a BMDM with EndoUmut, host double-stranded RNA (dsRNA) sensors (including MDA5, PKR, and OAS) are activated, resulting in robust transcription of type I IFN genes and rapid induction of apoptosis, the latter of which precludes the development of a potent inflammatory response.
cord-297834-me1ajoyb	2014	The immune response is energetically expensive for wild animals, thus the findings of experimental studies will be critical for understanding the ecoimmunology of reservoir hosts of hantaviruses [6, 7] , and experiments using wild rodents in natural or semi-natural environments [8, 9] will be required to validate laboratory findings. Currently, three laboratory infection systems have been developed to study hantavirus infections of reservoir hosts: Seoul virus (SEOV) infection of the Norway rat (Rattus norvegicus), Puumala virus (PUUV) infection of the bank vole (Myodes glareolus), and Sin Nombre virus (SNV) infection of the deer mouse (Peromyscus maniculatus) [12, 14, 16] . Experimental data have also shown that patterns of the expression of genes related to the immune response are different in infected males and females [32] , and it is likely these differences have important roles in hantavirus ecology.
cord-298525-hhcfrjrn	2018	The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light, which not only serves as a major determination of retinal image quality [1, 2] , but also provides an important metric of autonomic nervous system function [3] . The response latency, maximum constriction and pupil escape, and the corresponding constriction parameters (MCV, MCA and RCA; relative constriction amplitude) are dependent on the actions of the sphincter muscle and on the function of retinal photoreceptors, as well as the time consumed in the afferent and efferent pathway. The ability of pupillometry to detect subtle changes in pupillary reaction even when pupils are constricted has potential clinical significance and may provide a useful tool in the early detection, monitoring and management of brain injuries [89] .
cord-298668-ry49o0xj	2020	
cord-302082-aaokc182	2011	
cord-303319-v3iyur78	2019	
cord-303674-0xo2fiop	2019	In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. In this review, we discuss current advances and advantages of edible systems based on plants, algae, yeast, insect cells, and lactic acid bacteria and of the intradermal immunization route. Subsequently, the antigen(s) can be incorporated into different edible systems, as plants, algae, insects, or yeasts, or used for intradermal formulations to induce a mucosal protective response. Remarkably, some preclinical studies based on orally administrated Saccharomyces cerevisiae and developed for different infectious agents, such as HPV and Actinobacillus pleuropneumoniae, showed that this delivery system is able to induce a protective mucosal and a systemic immune response [68] [69] [70] . Another vaccine delivery route capable of triggering both systemic and mucosal immunities is the intradermal route, in which the antigen is delivered through the skin using recently developed self-administrable devices.
cord-305263-fgwf6wy3	2012	
cord-307202-iz1bo218	2014	Current asthma management involves a step-up and step-down approach based on asthma control with a large degree of heterogeneity in responses to the main drug classes currently in use: β(2)-adrenergic receptor agonists, corticosteroids, and leukotriene modifiers. Human studies have identified elevated numbers of cells expressing IL13 mRNA in the bronchial tissue of atopic and nonatopic asthmatic subjects [50] ; administration of recombinant IL13 in mouse lungs resulted in an increase in airway mucus secretion, development of subepithelial fibrosis, airway hyper-responsiveness (AHR), and eosinophilic airway inflammation-that is, several key features of the human disease [51] . While methods of stratifying asthma patients to specific treatments based on nongenetic factors such as clinical outcomes, cellular measures, or protein biomarkers have shown some success, a large body of work has investigated the potential of genetic markers as predictors of patient responses to existing therapies, i.e., pharmacogenetics.
cord-307229-wjx90xki	2020	
cord-309161-ceahghs1	2020	
cord-311331-l7dehit8	2020	The development of subunit vaccines without risk are considered as an essential need in combination with adequate delivery systems to obtain desired cell and humoral immune responses against infectious diseases. The characteristics of the nanoparticles have allowed targeting desired antigen-presenting cells to improve immunization strategies to induce protection. This chapter focuses on the nanoparticle-based vaccine formulations and the approaches used to realize efficient delivery of vaccines in order to induce host protective immunity against infectious diseases. The combination of the vaccine with the adjuvant or delivery system should be safe, stable, and have the ability to induce long-lived memory B and T cell responses, preferably with a single dose and a maximum of two doses and be free from strict storage requirements [9] . NPs have become an alternative to targeting vaccine delivery to immune cells, improving vaccine efficacy with slow release, easy antigen uptake, and induction of humoral and cellular responses [8] .
cord-311811-nrodyagi	2019	
cord-311823-85wj08gr	2008	
cord-314104-dkm8396y	2020	
cord-318272-spt0oea0	2020	''Nanovaccines'' have been explored to elicit a strong immune response with the advantages of nano-sized range, high antigen loading, enhanced immunogenicity, controlled antigen presentation, more retention in lymph nodes and promote patient compliance by a lower frequency of dosing. The role of different nanovaccines in activating various arms of immunity with an intent to abate the use of frequent booster doses as vaccines for tuberculosis, malaria, HIV (human immunodeficiency virus), influenza, and cancer are discussed. Polyanhydride-based nanoparticles encapsulating F1-V antigen when administered intranasally induced an immune response that persisted for 23 weeks and elicited a high anti-F1-V IgG1 antibody response post-vaccination and conferred long-lived protective immunity against Yersinia pestis infections compared to recombinant F1-V antigen [47] . Another interesting strategy for developing personalized biomimetic cancer nanovaccines is the use of cancer cell membrane coated virus for increased adjuvanticity, infectivity and oncolytic activities to generate a strong anti-tumor immune response.
cord-318599-drvjr7gq	2020	
cord-319448-gt6uqfrl	2003	
cord-320431-0877trhh	2020	In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Besides this innate "rapid response team, " the polarized epithelium of the human airways is also able to transport and apically release immunoglobulins that carry a J-chain (joining chain) by using its poly Ig receptor (pIgR) (145) (146) (147) that is expressed by all non-stratified epithelial cells (Figure 2) . After contact for example with HDM extracts, representing a major source of asthma associated allergens, TLR4 dependent activation of NFκB and protease induced injuries in airway epithelial cells lead to secretion of chemokines and cytokines like thymic stromal lymphopoietin (TSLP), GM-CSF, IL-25, and IL-33 (211) (212) (213) (214) (215) .
cord-322913-sq9mq6f1	2020	
cord-324143-ztj6o4ob	2020	
cord-324788-echu0zmf	2009	
cord-328935-mn8r972x	2015	Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. However, a recent study showed that an inactivated reassortant RV strain (CDC-9 strain) formulated with aluminum phosphate and administered systemically in gnotobiotic pigs resulted in induction of serum IgG antibody titers, coinciding with partial protection against shedding and diarrhea, suggesting that adjuvant may have stimulated local specific (gut IgA antibodies) or nonspecific immune responses, which were not assessed in this study (Wang et al., 2010) . Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs
cord-330583-ltkpt80u	2019	
cord-332838-i8fjwzm6	2008	Our choice of pathogens and authors has therefore resulted in reviews that cover many different types of infectious disease and a breadth of immune responses. The relationship between innate immune responses and viral success in the host population is also discussed by Drs Jessica Weaver and Stuart Isaacs (University of Pennsylvania School of Medicine) (6) with respect to monkeypox virus. Several of the reviews in this volume discuss the important role of T cells in viral, bacterial, and parasite emerging infections. For example, CD8 1 T cells play a major role in protective immunity during Plasmodium liver stage infection, as described by Dr Fidel Zavala and colleagues (Johns Hopkins University) (16) in their review of malaria immunity. While T cells can play a key role in protective immunity, they can also mediate considerable pathogenic effects. Dr Alan Rothman and colleagues (University of Massachusetts Medical School) (18) discuss the impact of T-cell responses on dengue virus infections.
cord-335871-zieuc7vk	2020	
cord-339694-sp212tai	2016	
cord-339935-tguhrqvz	2020	
cord-342317-m6axi18k	2020	
cord-343896-c40fry35	2020	
cord-344297-qqohijqi	2015	title: The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. [18] we used Affymetrix wholegenome chicken microarrays to examine the tracheal gene expression profiles of a line of birds known to be susceptible to IBV infection (line 15I) and a line known to show resistance (line N). Gene expression differences found in the susceptible 15I line between infected and control birds over days 2, 3 and 4 post infection were analysed, with a view to examining the innate host response to infection by IBV. Gene expression seen during the host response to IBV infection in the trachea of susceptible birds. Genes found to be differentially expressed between susceptible and resistant lines in response to IBV infection in the trachea.
cord-344985-3mu9rrql	2020	
cord-354790-xx6imhzb	2016	
cord-355541-5sctqkwr	2005