niryuu/sni-each-converted huggingface dataset:
Paragraph: Lipid rafts are micro-domains of ordered lipids (L o phase) in biological membranes. The L o phase of cellular membranes can be isolated from disordered lipids (L d phase) after treatment with 1 % Triton X-100 at 4°C in which the L o phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with<5 mM methyl-ß-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multilamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein-cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the L o phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context. 
 Title: Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells
Output: False
Paragraph: Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structureeactivity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates. 
 Title: Therapeutic potential of coumarins as antiviral agents
Output: True
Paragraph: Background: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. Methods: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. Results: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. Conclusions: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. 
 Title: Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis
Output: False
Paragraph: The analysis of T cell receptor diversity provides a clinically relevant and sensitive marker of repertoire loss, gain, or skewing. Spectratyping is a broadly utilized technique to measure global TCR diversity by the analysis of the lengths of CDR3 fragments in each Vβ family. However the common use of large numbers of T cells to obtain a global view of TCR Vβ CDR3 diversity has restricted spectratyping analyses when limited T-cell numbers are available in clinical setting, such as following transplant regimens. We here demonstrate that one hundred thousand T cells are sufficient to obtain a robust, highly reproducible measure of the global TCR Vβ repertoire diversity among twenty Vβ families in human peripheral blood. We also show that use of lower cell number results not in a dwindling of observed diversity but rather in non-reproducible patterns in replicate spectratypes. Finally, we report here a simple to use but sensitive method to quantify repertoire divergence in patient samples by comparison to a standard repertoire profile we generated from fifteen normal donors. We provide examples using this method to statistically evaluate the changes in the global TCR Vβ repertoire diversity that may take place during T subset immune reconstitution after hematopoietic stem cell transplantation or after immune modulating therapies. TCR Vβ CDR3 repertoire diversity in human peripheral blood; spectratype; immune reconstitution; hematopoietic stem cell transplantation Corresponding author: Sarfraz A. Memon, M.D., Experimental Transplantation and Immunology Branch, 
 Title: Quantitative Analysis of T Cell Receptor Diversity in Clinical Samples of Human Peripheral Blood
Output: False
Paragraph: Integrative Physiology, a section of the journal Frontiers in Physiology ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation. 
 Title: A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems
Output: True
Paragraph: This data article informs about Chiropteran diversity, new records, ecosystem services and possible pathogen carriers in fragmented forests (sub-divided by utility corridors, man-made structures, untouched and secondary plantations) within districts Setiu (Setiu Research Station), Hulu Terengganu (Saok and Lasir waterfalls) and Besut (Gunung Tebu Forest Reserve) of state Terengganu, Peninsular Malaysia. These bats were captured using harp traps and mist nets that were set 10 m apart across flyways, streams and less cluttered trees in the 50 m Â 50 m transect zones (identified at each site). All animals were distinguished by morphology and gender before their release at the site of capture. The data comprise of five bat family groups Hipposideridae, Megadermatidae, Pteropodidae, Rhinolophidae and Vespertilionidae. It is interesting to note that untouched Saok Waterfalls is home to wide variety of bats listed (68.8%), followed by secondary forests of Gunung Tebu Forest Reserve (24.8%), untouched Lasir Waterfalls (4.8%) and lastly, Setiu Research Station as least favored (1.6%). Chiroptera like Cynopterus brachyotis (n ¼ 23, 37.7%), Hipposideros bicolor (n ¼ 6, 9.8%) and Scotophilus kuhli (n ¼ 6, 9.8%) were most dominant in the checklist whereas Hipposideros armiger, 
 Title: Linkages between Chiropteran diversity and ecosystem services for sustainable fragmented forest conservation
Output: True
Paragraph: The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, "respiratory droplet" transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease. 
 Title: What was the primary mode of smallpox transmission? Implications for biodefense
Output: False
Paragraph: Diarrhoeic faeces from about 500 dogs were examined by negative stain electron microscopy. As well as parvovims, and some of the other recognised viral causes of gastroenteritis, unusual "viruslike" particles were observed in about 8% of the samples. The particles were spherical, 100 nm to 300 nm in diameter, and surrounded by a thick wall penetrated by numerous pores. An additional 74 samples of normal faeces yielded no "virus-like" particles. We do not know the nature of these particles. 
 Title: Shedding of "virus-like' ' particles in canine faeces
Output: False
Paragraph: Diarrhea represents one of the most frequent disorders in dogs. In puppies, degradation of feces quality is associated with a reduced daily weight gain and an increased risk of death. Prevention of diarrhea in puppies requires a global approach encompassing enteropathogens, environment and management practices especially when housed in groups. The purpose of this study was to determine prevalence of enteropathogens in puppies in breeding kennels and to identify risk factors of diarrhea. Two hundred and sixty six puppies (between 5 and 14 weeks of age) from 29 French breeding kennels were included. For each kennel, data about environment, management of the kennel and puppies' characteristics (age, sex and breed) were collected. For each puppy, fecal consistency and fecal excretion of enteropathogens (viruses and parasites) was evaluated. At least one enteropathogen was identified in 77.1% of puppies and 24.8% of puppies presented abnormal feces. The main risk factor of weaning diarrhea was fecal excretion of canine parvovirus type 2 (odds ratio = 5; confidence interval 95%: 1.7-14.7). A targeted sanitary and medical prophylaxis against canine parvovirus type 2 should be implemented to decrease risk of weaning diarrhea. 
 Title: Risk factors of weaning diarrhea in puppies housed in breeding kennels-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/)
Output: True
Paragraph: We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996-2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8-19.8), 2.9 (1.0-5.0), and 11.9 (8.3-15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries. 
 Title: Influenza-associated Deaths in Tropical Singapore Influenza-associated Deaths in Tropical Singapore
Output: True
Paragraph: Object-induced three-way object concept Attribute-induced three-way attribute concept Discernibility attribute set a b s t r a c t Three-way concept analysis is a newly proposed area of formal concept analysis from which one can obtain both the inclusion decision and the exclusion decision. In general, given a context, some attributes may not be essential in three-way concept analysis, such as forming three-way concept lattice. So in this paper, we study the attribute reductions of three-way concept lattices in order to make the data easily be understood. Firstly, based on different criteria generated from object-induced three-way concept (OEconcept), four kinds of attribute reductions are proposed. The four reductions together embody different characteristics of a formal context and can be used in different occasions. Secondly, we discuss their relationships, including their advantages and disadvantages and the relationships among consistent sets and among the cores. Thirdly, based on attribute-induced three-way concept (AE-concept), we also give four attribute-induced three-way attribute reductions and discuss their relationships. Finally, the approaches to computing these attribute reductions are presented and the obtained results are demonstrated and verified by an empirical case. In this paper, we systematically investigate the attribute reductions of threeway concept lattices which enriches the study of formal concept analysis. 
 Title: Knowle dge-Base d Systems The attribute reductions of three-way concept lattices
Output: True
Paragraph: In this second part of the chapter on underutilized spices, nine spices are discussed briefl y. They are mango ginger, fragrant pandan, pink pepper, rue, sumac, savory and wasabi. Morphology, chemical composition, medicinal and culinary uses are given briefl y in each of these spices. In addition short notes on 12 lesser known spices are provided; these are blue fenugreek, boldo leaves, chameleon plant, cicely, cresses, epazote, fi nger root, gale, lemon myrtle, Mexican pepper leaf, Tasmanian pepper and water pepper. 
 Title: Other herbs and spices: mango ginger to wasabi
Output: False
Paragraph: In this study, we compare the development of infection and/or disease in Beagle dogs intradermally infected with Leishmania chagasi, in the presence or absence of Lutzomyia longipalpis saliva, with those of intravenously infected animals. Spleen samples of all the animals inoculated with parasites had positive polymerase chain reaction tests for Leishmania DNA. Positive spleen cultures for Leishmania were detected earlier (P ≤ 0.018) and were more frequent (five out of the five animals) in intravenously infected animals than in the intradermally infected animals, in presence (two out of the six animals) or absence (three out of the five animals) of salivary gland lysate of L. longipalpis. Significant increase in serum antibodies against Leishmania was observed only in the intravenously infected group (P = 0.004). In addition, dogs with infection confirmed by isolation of amastigotes or detection of parasite DNA were, nevertheless, negative for anti-Leishmania antibodies up to 5 months or more after infection. Only animals of the intravenously infected group developed progressive decreases in hematocrit (Pearson r = −0.8076, P = 0.0026) and hemoglobin (Pearson r = −0.8403, P = 0.0012) during the infection period. No significant difference in the course of infection was observed between groups of intradermally infected animals. M. Paranhos-Silva et al. / Veterinary Parasitology 114 (2003) 97-111 inoculation of dogs with Leishmania produces an asymptomatic form of infection. It also fails to show an advantage in using L. longipalpis saliva as an infection-enhancing agent in experimental canine leishmaniasis. 
 Title: A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva
Output: True
Paragraph: Objectives: To improve diagnosis as part of laboratory surveillance in Taiwan, influenza-like illness (ILI) surveillance was conducted using a new multiplex PCR assay (FilmArray) and the results compared to those of conventional methods The study was performed during the winter months. Methods: Throat swabs from patients with an ILI presenting to physicians in sentinel practices were collected during the 2016-2017 influenza season. Results: A total of 52 samples tested positive by FilmArray Respiratory Panel. Forty percent were influenza A virus, and subtype H3N2 virus was the major epidemic strain. However, nearly 60% of ILI cases seen at sentinel sites were caused by non-influenza pathogens. The results of the FilmArray assay and cell culture were identical, and this assay was more sensitive than a rapid influenza diagnostic test. Genetic analyses revealed new influenza A H3N2 variants belonging to a novel subclade 3C.2a2. Conclusions: The FilmArray assay facilitates urgent testing and laboratory surveillance for common viral and bacterial respiratory pathogens. This study demonstrated the use of a highly sensitive assay using clinical samples that is feasible for application worldwide. This may lead to an increased rate of diagnosis of viral infections and to improved patient outcomes, and in particular to a reduction in the overuse of antibiotics and antivirals. 
 Title: Surveillance of upper respiratory infections using a new multiplex PCR assay compared to conventional methods during the influenza season in Taiwan
Output: False
Paragraph: Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL, and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Based on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate. 
 Title: S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic Diarrhea Virus Is an Important Determinant of Virulence in Piglets
Output: False
Paragraph: Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination. 
 Title: Lipid-Based Particles: versatile Delivery Systems for Mucosal vaccination against infection
Output: False
Paragraph: Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of anti-norovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection. . Accession Codes. The coordinates and structure factors for norovirus 3CL protease in complex with inhibitors have been deposited to the Protein Databank with the accession codes NVpro:17 (4XBB), NVPro:44-h (4XBC) and NVPro:44-o (4XBD). We initially focused on the design of peptidyl transition state inhibitors of NV 3CLpro that incorporate in their structure a recognition element (a peptidyl fragment) that is congruent with the known substrate specificity of the enzyme (vide supra) and a warhead (aldehyde or α-ketoamide), latent warhead (bisulfite adduct) or transition state mimic (α- Kankanamalage et al. The synthesized compounds were evaluated for their inhibitory activity against NV 3CLpro, as well as their anti-norovirus activity in a cell-based replicon system, as previously Kankanamalage et al. In order to evaluate the specific interactions between the enzyme and the αhydroxyphosphonate inhibitors, inhibitor 17 was incubated with NV 3CLpro in Tris buffer, pH 8.0. Surprisingly, the enzyme-inhibitor complex formed corresponded to the complex formed between aldehyde 16 and 3CL protease. The formation of this complex indicates initial non-enzymatic (buffer)-or enzyme-catalyzed conversion of α-hydroxyphosphonate 17 to the corresponding aldehyde 16, followed by the formation of a tetrahedral adduct with the active site cysteine (Cys139). Studies aimed at ascertaining the validity of this hypothesis are in progress. The ensemble of hydrogen bonding and hydrophobic interactions Kankanamalage et al.  
 Title: Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic, Cell- Based, and In Vivo Studies
Output: False
Paragraph: Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5 + TCF1 + CD8 + T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5 + CD8 + T cell expansion in an IL-27-and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8 + T cells. We found that CD8 + T cell-intrinsic IL-27 signaling safeguards the ability of TCF1 hi cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer. 
 Title: IL-27 promotes the expansion of self-renewing CD8 + T cells in persistent viral infection
Output: False
Paragraph: Recent years have seen the development of numerous methodologies for reconstructing transmission trees in infectious disease outbreaks from densely sampled whole genome sequence data. However, a fundamental and as of yet poorly addressed limitation of such approaches is the requirement for genetic diversity to arise on epidemiological timescales. Specifically, the position of infected individuals in a transmission tree can only be resolved by genetic data if mutations have accumulated between the sampled pathogen genomes. To quantify and compare the useful genetic diversity expected from genetic data in different pathogen outbreaks, we introduce here the concept of 'transmission divergence', defined as the number of mutations separating whole genome sequences sampled from transmission pairs. Using parameter values obtained by literature review, we simulate outbreak scenarios alongside sequence evolution using two models described in the literature to describe transmission divergence of ten major outbreak-causing pathogens. We find that while mean values vary significantly between the pathogens considered, their transmission divergence is generally very low, with many outbreaks characterised by large numbers of genetically identical transmission pairs. We describe the impact of transmission divergence on our ability to reconstruct outbreaks using two outbreak reconstruction tools, the R packages outbreaker and phybreak, and demonstrate that, in agreement with previous observations, genetic sequence data of rapidly evolving pathogens such as RNA viruses can provide valuable information on individual transmission events. Conversely, sequence data of pathogens with lower mean transmission divergence, including Streptococcus pneumoniae, Shigella sonnei and Clostridium difficile, provide little to no information about individual transmission events. Our results highlight the informational limitations of genetic sequence data in certain outbreak scenarios, and demonstrate the need to expand the toolkit of outbreak reconstruction tools to integrate other types of epidemiological data. The increasing availability of genetic sequence data has sparked an interest in using pathogen whole genome sequences to reconstruct the history of individual transmission events PLOS Pathogens | https://doi. 
 Title: When are pathogen genome sequences informative of transmission events?
Output: True
Paragraph: Background: The population of dogs and cats passing through rescue shelters may be subject to compromised welfare and increased susceptibility to disease. Little information exists to describe this population, its dynamics and associated management practices. The aim of this study was to carry out a census of un-owned cats and dogs in the UK in 2010, and to document the origins, destinations, husbandry and costs associated with the care of these animals. 
 Title: Demographics and economic burden of un-owned cats and dogs in the UK: results of a 2010 census Stavisky et al. Demographics and economic burden of un-owned cats and dogs in the UK: results of a 2010 census
Output: True
Paragraph: Miller virulent strain of transmissible gastroenteritis virus (TGEV) were generated and characterized. In a cell culture immunofluorescence (CCIF) assay, three MAbs directed against peplomer protein (E 2) had perinuclear fluorescence and four unclassified MAbs showed cell membrane fluorescence. Six of these seven MAbs neutralized both attenuated and virulent TGEV, and the seventh (an unclassified MAb) neutralized only the latter virus. Two MAbs able to bind the cell membrane of infected cells had low neutralizing antibody titers (8 to 72) but were able to distinguish between virulent and attenuated TGEV (9-to 72-fold differences in neutralizing titers). Two E 2-specific MAbs had higher neutralizing antibody titers (782 to 34,117) and showed 4-to 13-fold differences in titers against the attenuated and virulent TGEV strains. Five MAbs which were specific for nucleocapsid (N) protein had cytoplasmic, particulate fluorescence in CCIF, and did not neutralize TGEV. Comparison of CCIF antibody titers of MAbs to the virulent and attenuated strains of TGEV indicated that differences existed in titers of most E 2 and all N-specific MAbs, with titers consistently higher against virulent TGEV (homologous strain). Hyperimmune antisera prepared in gnotobiotic pigs against the attenuated, virulent and a recent isolate ofTGEV immunoprecipitated the 3 major structural proteins of both the attenuated and virulent TGEV strains. Relative mot. wt. differences in the E 1 and E 2 proteins between the two virus strains were revealed using either the hyperimmune pig sera or MAbs. In addition to the 48 K N protein, a 44 K protein was coimmunoprecipitated by the hyperimmune sera and MAbs, but mainly from lysates of attenuated TGEV. 
 Title: Monoclonal antibodies to a virulent strain of transmissible gastroenteritis virus: comparison of reactivity with virulent and attenuated virus
Output: False
Paragraph: The Global Polio Laboratory Network (GPLN) began building in the late 1980s on a 3-tiered structure of 146 laboratories with different and complementary technical and support capacities (poliovirus isolation, molecular strain characterization including sequencing, quality assurance, and research). The purpose of this network is to provide timely and accurate laboratory results to the Global Polio Eradication Initiative. Deeply integrated with field case-based surveillance, it ultimately provides molecular epidemiological data from polioviruses used to inform programmatic and immunization activities. This network of global coverage requires substantial investments in laboratory infrastructure, equipment, supplies, reagents, quality assurance, staffing and training, often in resource-limited settings. The GPLN has not only developed country capacities, but it also serves as a model to other global laboratory networks for vaccinepreventable diseases that will endure after the polio eradication goal is achieved. Leveraging lessons learned during past 27 years, the authors discuss options for transitioning GPLN assets to support control of other viral vaccine-preventable, emerging, and reemerging diseases. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 IGO (CC BY 3.0 IGO) License (https://creativecommons.org/licenses/by/3.0/igo/) which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 
 Title: The Global Polio Laboratory Network as a Platform for the Viral Vaccine-Preventable and Emerging Diseases Laboratory Networks HHS Public Access
Output: True
Paragraph: Theiler's murine encephalomyelitis virus (TMEV) and other neurotropic virus infections result in degeneration of each component of the neuron: apoptosis of the cell body, axonal (Wallerian) degeneration, and dendritic and synaptic pathology. In general, axonal degeneration is detrimental for hosts. However, axonal degeneration can be beneficial in the case of infection with neurotropic viruses that spread in the CNS using axonal transport. C57BL/Wld S (Wld S , Wallerian degeneration slow mutant) mice are protected from axonal degeneration. Wld S mice infected with the neurovirulent GDVII strain of TMEV are more resistant to virus infection than wild-type mice, suggesting that axonal preservation contributes to the resistance. By contrast, infection with the less virulent Daniels strain of TMEV results in high levels of virus propagation in the CNS, suggesting that prolonged survival of axons in Wld S mice favors virus spread. Thus, axonal degeneration might be a beneficial self-destruct mechanism that limits the spread of neurotropic viruses, in the case of less virulent virus infection. We hypothesize that neurons use 'built-in' self-destruct protection machinery (compartmental neurodegeneration) against neurotropic virus infection, since the CNS is an immunologically privileged site. Early induction of apoptosis in the neuronal cell body limits virus replication. Wallerian degeneration of the axon prevents axonal transport of virus. Dendritic and synaptic degeneration blocks virus transmission at synapses. Thus, the balance between neurodegeneration and virus propagation may be taken into account in the future design of neuroprotective therapy. Neurons are the transmitting cells of the nervous system and communicate by chemical and electrical means. A neuron can be divided into different components: cell body (soma), a longer cell process called an axon, branching processes called dendrites and synapses. A neuron transmits information via the axon, which terminates at a synapse for conveying ongoing signals, while dendrites integrate incoming signals. Since axons as well as their neuronal cell bodies do not usually regenerate in the CNS, axonal damage often results in permanent neurological deficits. Axonal degeneration in the CNS can be seen in several neurological conditions, such as neurodegenerative diseases (e.g., amyotrophic lateral sclerosis and neuroaxonal dystrophy) [1], traumatic lesions and infections [2] [3] [4] [5] . 
 Title: Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection NIH Public Access
Output: False
Paragraph: Multiple sclerosis (MS) is the prototypic inflammatory disease of the central nervous system (CNS) characterized by multifocal areas of demyelination, axonal damage, activation of glial cells, and immune cell infiltration. Despite intensive years of research, the etiology of this neurological disorder remains elusive. Nevertheless, the abundance of immune cells such as T lymphocytes and their products in CNS lesions of MS patients supports the notion that MS is an immune-mediated disorder. An important body of evidence gathered from MS animal models such as experimental autoimmune encephalomyelitis (EAE), points to the central contribution of CD4 T lymphocytes in disease pathogenesis. Both Th1 (producing interferon-γ) and Th17 (producing interleukin 17) CD4 T lymphocytes targeting CNS self-antigens have been implicated in MS and EAE pathobiology. Moreover, several publications suggest that CD8 T lymphocytes also participate in the development of MS lesions. The migration of activated T lymphocytes from the periphery into the CNS has been identified as a crucial step in the formation of MS lesions. Several factors promote such T cell extravasation including: molecules (e.g., cell adhesion molecules) implicated in the T cell-blood brain barrier interaction, and chemokines produced by neural cells. Finally, once in the CNS, T lymphocytes need to be reactivated by local antigen presenting cells prior to enter the parenchyma where they can initiate damage. Further investigations will be necessary to elucidate the impact of environmental factors (e.g., gut microbiota) and CNS intrinsic properties (e.g., microglial activation) on this inflammatory neurological disease. 
 Title: Multiple Sclerosis and T Lymphocytes: An Entangled Story
Output: True
Paragraph: Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules. 
 Title: The VIZIER project: Preparedness against pathogenic RNA viruses
Output: False
Paragraph: Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies-either where volunteers are infected with a disease or where existing cases are recruited-in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens-influenza and norovirus-as well as Ebola virus disease. 
 Title: Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry
Output: True
Paragraph: Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. The TCI device was a hydrogel patch (antigen-free) applied to the left brachial medial skin of 22 healthy volunteers for 48 h. Next, the hydrogel patch, containing 2 mg tetanus toxoid (TT) and 2 mg diphtheria toxoid (DT) as the TCI formulation, was applied to 27 healthy volunteers for 24 h and some volunteers were vaccinated again by TCI formulation. For safety assessment, the patch application site was observed to assess local adverse events, and systemic adverse events were determined by a blood test. The antigen-free hydrogel patch and TCI formulation containing TT and DT did not induce local or systemic severe adverse events. For vaccine efficacy estimation, toxoid-specific serum antibody titers were determined by ELISA and the toxin-neutralizing activity of the induced antibody was evaluated in a passive-challenge experiment. The anti-TT IgG titer and the anti-DT IgG titer increased, and a significant effect was detected by paired t-test. The antibody titers were maintained at higher level than that before vaccination for at least 1 year. Moreover, toxoid-specific antibodies were produced by the second vaccination in some subjects. Antibodies induced by application of the TCI formulation neutralized the toxin and prevented toxic death in mice. In addition, changes in the skin condition due to application of the TCI formulation were observed under in vivo confocal Raman spectroscopy. The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases. 
 Title: Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria
Output: True
Paragraph: Background: Emerging infectious diseases pose a significant risk to public health. Methods for rapid detection of pathogens are needed to effectively treat these diseases. Recently, we developed new methods for the rapid determination of viral RNA sequences, RDV ver1.0 and ver2.0. We demonstrated that these methods were able to simultaneously detect cDNA fragments of many different viruses without using sequence specific primers. However, some species of viruses, including the Yokose virus (YOKV), a flavivirus, could not be detected using the conventional procedures. Objective: The RDV method was further modified to reduce the candidate PCR primer sets. Study design: Primer sets were reduced to 256 sets in the improved RDV ver3.0, and theoretically, all viral cDNA fragments ligated by two kinds of adaptors after digestion by two restriction enzymes could be amplified in the PCR step for direct sequencing. Results: We succeeded in obtaining 118 YOKV cDNA fragments of the 141 sequence fragments. The cDNA fragments covered diverse range of viral genome. Conclusion: We were able to reduce the combinations of PCR primer sets used in the RDV method. This RDV method ver3.0 has a potential to detect viral cDNA fragments of both known and unknown RNA viruses rapidly and conveniently. 
 Title: Ligation-mediated amplification for effective rapid determination of viral RNA sequences (RDV)
Output: True
Paragraph: This study investigates the impacts of high-speed rail (HSR) on domestic air transportation in China using a new comprehensive modeling framework utilizing both demand and supply perspectives. For the first time the assessment was conducted using an improved panel regression model by taking into account of the detailed opening schedules of various HSR services during the period 2001-2014. The research findings reveal that the deployed HSR services have a significant substitutional effect on domestic air transportation in China, but the effect varies across different HSR routes, travel distance and city type. Specifically, the research found a decrease in domestic passengers of 28.2%, in flights of 24.6% and in seat capacity of 27.9% after the introduction of HSR services. The impacts are found much stronger among those air routes that connect major hub within a distance range of 500 to 800 km. The uneven nature of the impact can be seen in the different experiences of selected cities. For example, air travel declined approximately 45% after commencement of the Wuhan-Guangzhou HSR, whereas it fell by 34% after the opening of the Beijing-Shanghai HSR. http://dx. 
 Title: Impacts of high-speed rail on domestic air transportation in China
Output: True
Paragraph: Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre' syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR − / − ) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR − / − mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans. 
 Title: ARTICLE In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine
Output: True
Paragraph: In many biological systems, proteins interact with other organic molecules to produce indispensable functions, in which molecular recognition phenomena are essential. Proteins have kept or gained their functions during molecular evolution. Their functions seem to be flexible, and a few amino acid substitutions sometimes cause drastic changes in function. In order to monitor and predict such drastic changes in the early stages in target populations, we need to identify patterns of structural changes during molecular evolution causing decreases or increases in the binding affinity of protein complexes. In previous work, we developed a likelihood-based index to quantify the degree to which a sequence fits a given structure. This index was named the sequence-structure fitness (SSF) and is calculated empirically based on amino acid preferences and pairwise interactions in the structural environment present in template structures. In the present work, we used the SSF to develop an index to measure the binding affinity of protein-protein complexes defined as the log likelihood ratio, contrasting the fitness of the sequences to the structure of the complex and that of the uncomplexed proteins. We applied the developed index to the complexes formed between influenza A hemagglutinin (HA) and four antibodies. The antibody-antigen binding region of HA is under strong selection pressure by the host immune system. Hence, examination of the long-term adaptation of HA to the four antibodies could reveal the strategy of the molecular evolution of HA. Two antibodies cover the HA receptor-binding region, while the other two bind away from the receptor-binding region. By focusing on branches with a significant decline in binding ability, we could detect key amino acid replacements and investigate the mechanism via conditional probabilities. The contrast between the adaptations to the two types of antibodies suggests that the virus adapts to the immune system at the cost of structural change. 
 Title: A Likelihood-based Index of Protein-Protein Binding Affinities with Application to Influenza HA Escape from Antibodies
Output: False