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                <text>Predicting peptide structures in native proteins from physical simulations of fragments.</text>
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                <text>Vincent A. Voelz, M Scott Shell, Ken A. Dill</text>
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                <text>It has long been proposed that much of the information encoding how a protein folds is contained locally in the peptide chain. Here we present a large-scale simulation study designed to examine the extent to which conformations of peptide fragments in water predict native conformations in proteins. We perform replica exchange molecular dynamics (REMD) simulations of 872 8-mer, 12-mer, and 16-mer peptide fragments from 13 proteins using the AMBER 96 force field and the OBC implicit solvent model. To analyze the simulations, we compute various contact-based metrics, such as contact probability, and then apply Bayesian classifier methods to infer which metastable contacts are likely to be native vs. non-native. We find that a simple measure, the observed contact probability, is largely more predictive of a peptide's native structure in the protein than combinations of metrics or multi-body components. Our best classification model is a logistic regression model that can achieve up to 63% correct classifications for 8-mers, 71% for 12-mers, and 76% for 16-mers. We validate these results on fragments of a protein outside our training set. We conclude that local structure provides information to solve some but not all of the conformational search problem. These results help improve our understanding of folding mechanisms, and have implications for improving physics-based conformational sampling and structure prediction using all-atom molecular simulations.</text>
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                <text>DOI: 10.1371/journal.pcbi.1000281</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of US swine origin influenza A H3N2v virus.</text>
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                <text>Simon Cauchemez, Scott Epperson, Matthew Biggerstaff, David Swerdlow, Lyn Finelli, Neil M. Ferguson</text>
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                <text>BACKGROUND:Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS:Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS:We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.</text>
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                <text>DOI: 10.1371/journal.pmed.1001399</text>
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                <text>PLoS Medicine</text>
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                <text>Feature selection methods for identifying genetic determinants of host species in RNA viruses.</text>
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                <text>Ricardo Águas, Neil M. Ferguson</text>
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                <text>Despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. RNA viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen--as reflected by the recent emergence of SARS and Influenza for example. Here, we show how feature selection techniques can be used to reliably classify viral sequences by host species, and to identify the crucial minority of host-specific sites in pathogen genomic data. The variability in alleles at those sites can be translated into prediction probabilities that a particular pathogen isolate is adapted to a given host. We illustrate the power of these methods by: 1) identifying the sites explaining SARS coronavirus differences between human, bat and palm civet samples; 2) showing how cross species jumps of rabies virus among bat populations can be readily identified; and 3) de novo identification of likely functional influenza host discriminant markers.</text>
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                <text>DOI: 10.1371/journal.pcbi.1003254</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>A k-mer-based method for the identification of phenotype-associated genomic biomarkers and predicting phenotypes of sequenced bacteria.</text>
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                <text>Erki Aun, Age Brauer, Veljo Kisand, Tanel Tenson, Maido Remm</text>
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                <text>We have developed an easy-to-use and memory-efficient method called PhenotypeSeeker that (a) identifies phenotype-specific k-mers, (b) generates a k-mer-based statistical model for predicting a given phenotype and (c) predicts the phenotype from the sequencing data of a given bacterial isolate. The method was validated on 167 Klebsiella pneumoniae isolates (virulence), 200 Pseudomonas aeruginosa isolates (ciprofloxacin resistance) and 459 Clostridium difficile isolates (azithromycin resistance). The phenotype prediction models trained from these datasets obtained the F1-measure of 0.88 on the K. pneumoniae test set, 0.88 on the P. aeruginosa test set and 0.97 on the C. difficile test set. The F1-measures were the same for assembled sequences and raw sequencing data; however, building the model from assembled genomes is significantly faster. On these datasets, the model building on a mid-range Linux server takes approximately 3 to 5 hours per phenotype if assembled genomes are used and 10 hours per phenotype if raw sequencing data are used. The phenotype prediction from assembled genomes takes less than one second per isolate. Thus, PhenotypeSeeker should be well-suited for predicting phenotypes from large sequencing datasets. PhenotypeSeeker is implemented in Python programming language, is open-source software and is available at GitHub (https://github.com/bioinfo-ut/PhenotypeSeeker/).</text>
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                <text>DOI: 10.1371/journal.pcbi.1006434</text>
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                <text>IL-12 RB1 genetic variants contribute to human susceptibility to severe acute respiratory syndrome infection among Chinese.</text>
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              <elementText elementTextId="972">
                <text>Fang Tang, Wei Liu, Fang Zhang, Zhong-Tao Xin, Mao-Ti Wei, Pan-He Zhang, Hong Yang, Hinh Ly, Wu-Chun Cao</text>
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            <description>An account of the resource</description>
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              <elementText elementTextId="973">
                <text>BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of interleukin (IL)-12 receptor B1 (IL-12RB1) affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in Chinese SARS patients and healthy controls. The genotypes of 4SNPs on IL-12 RB1 gene, +705A/G,+1158T/C, +1196G/C and +1664 C/T, were determined by PCR-RFLP. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm. RESULTS: Comparison between patients and close contacts showed that individuals with the +1664 C/T (CT and TT) genotype had a 2.09-fold (95% confidence interval [CI], 1.90-7.16) and 2.34-fold (95% CI, 1.79-13.37) increased risk of developing SARS, respectively. For any of the other three polymorphisms, however, no significant difference can be detected in allele or genotype frequencies between patients and controls. Additionally, estimation of the frequencies of multiple-locus haplotypes revealed potential risk haplotypes (GCCT) for SARS infection. CONCLUSIONS: Our data indicate that genetic variants of IL12RB1confer genetic susceptibility to SARS infection, but not necessary associated with the progression of the disease in Chinese population.</text>
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                <text>2008</text>
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              <elementText elementTextId="975">
                <text>DOI: 10.1371/journal.pone.0002183</text>
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              <elementText elementTextId="976">
                <text>PLoS ONE</text>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
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              <elementText elementTextId="977">
                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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            <elementTextContainer>
              <elementText elementTextId="979">
                <text>EN</text>
              </elementText>
            </elementTextContainer>
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  <item itemId="104" public="1" featured="0">
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
                </elementText>
              </elementTextContainer>
            </element>
          </elementContainer>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
    </itemType>
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      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
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              <elementText elementTextId="980">
                <text>SARS: systematic review of treatment effects.</text>
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          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="981">
                <text>Lauren J. Stockman, Richard Bellamy, Paul Garner</text>
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          <element elementId="41">
            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="982">
                <text>BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="983">
                <text>2006</text>
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          <element elementId="43">
            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
            <elementTextContainer>
              <elementText elementTextId="984">
                <text>DOI: 10.1371/journal.pmed.0030343</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="985">
                <text>PLoS Medicine</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="986">
                <text>Public Library of Science (PLoS)</text>
              </elementText>
            </elementTextContainer>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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              <elementText elementTextId="987">
                <text>Medicine</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="44">
            <name>Language</name>
            <description>A language of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="988">
                <text>EN</text>
              </elementText>
            </elementTextContainer>
          </element>
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  <item itemId="105" public="1" featured="0">
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                <elementText elementTextId="1">
                  <text>Coronavirus</text>
                </elementText>
              </elementTextContainer>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
              <elementTextContainer>
                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
                </elementText>
              </elementTextContainer>
            </element>
          </elementContainer>
        </elementSet>
      </elementSetContainer>
    </collection>
    <itemType itemTypeId="1">
      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
    </itemType>
    <elementSetContainer>
      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
            <elementTextContainer>
              <elementText elementTextId="989">
                <text>Communicable disease control in China: From Mao to now</text>
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          </element>
          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="990">
                <text>David Hipgrave</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="41">
            <name>Description</name>
            <description>An account of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="991">
                <text>China’s progress on communicable disease control (CDC) in the 30 years after establishment of the People’s Republic in 1949 is widely regarded as remarkable. Life expectancy soared by around 30 years, infant mortality plummeted and smallpox, sexually transmitted diseases and many other infections were either eliminated or decreased massively in incidence, largely as a result of CDC. By the mid-1970s, China was already undergoing the epidemiologic transition, years ahead of other nations of similar economic status. These early successes can be attributed initially to population mobilization, mass campaigns and a focus on sanitation, hygiene, clean water and clean delivery, and occurred despite political instability and slow economic progress. The 10-year Cultural Revolution from 1966 brought many hardships, but also clinical care and continuing public health programs to the masses through community-funded medical schemes and the establishment of community-based health workers. These people-focused approaches broke down with China’s market reforms from 1980. Village doctors turned to private practice as community funding ceased, and the attention paid to rural public health declined. CDC relied on vertical programs, some of them successful (such as elimination of lymphatic filariasis and child immunisation), but others (such as control of schistosomiasis and tuberculosis) demonstrating only intermittent progress due to failed strategies or reliance on support by the poorest governments and health workers, who could not or would not collaborate. In addition, China’s laissez-faire approach to public health placed it at great risk, as evidenced by the outbreak in 2003 of the Severe Acute Respiratory Syndrome. Since then, major changes to disease reporting, the priority given to CDC including through major new domestic resources and reform of China’s health system offer encouragement for CDC. While decentralized funding and varying quality diagnosis, reporting and treatment of infectious diseases remain major challenges, national priority on CDC in China is high.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="992">
                <text>2011</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="49">
            <name>Subject</name>
            <description>The topic of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="993">
                <text>China, progress, Communicable disease control</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="43">
            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
            <elementTextContainer>
              <elementText elementTextId="994">
                <text>DOI: </text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="995">
                <text>Journal of Global Health</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="996">
                <text>Edinburgh University Global Health Society</text>
              </elementText>
            </elementTextContainer>
          </element>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
            <elementTextContainer>
              <elementText elementTextId="997">
                <text>Public aspects of medicine, Medicine</text>
              </elementText>
            </elementTextContainer>
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            <description>A language of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="998">
                <text>EN</text>
              </elementText>
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  <item itemId="106" public="1" featured="0">
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
              <elementTextContainer>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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          <element elementId="50">
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                <text>Ethical Perspectives on the Middle East Respiratory Syndrome Coronavirus Epidemic in Korea</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1000">
                <text>Ock-Joo KIM</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="41">
            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="1001">
                <text>Ethical considerations are essential in planning for and responding to outbreaks of infectious diseases. During the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Republic of Korea in 2015, serious challenges emerged regarding important ethical issues, such as transparency and the protection of privacy. The development of bioethics in Korea has been influenced by individualistic perspectives applied in clinical contexts, leading to a paucity of ethical perspectives relevant to population-level phenomena such as outbreaks. Alternative theories of public health ethics include the perspectives of relational autonomy and the patient as victim and vector. Public health actions need to incorporate clear and systematic procedures founded upon ethical principles. The MERS-CoV epidemic in Korea created significant public support for more aggressive early interventions in future outbreaks. This trend makes it all the more imperative for ethical principles and procedures to be implemented in future planning and responses to outbreaks in order to promote perceptions of legitimacy and civic participation.</text>
              </elementText>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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              <elementText elementTextId="1002">
                <text>2016</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="49">
            <name>Subject</name>
            <description>The topic of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1003">
                <text>Middle East respiratory syndrome coronavirus, Public Health, Ethics, ethical principles, epidemic, Republic of Korea</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="43">
            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="1004">
                <text>DOI: 10.3961/jpmph.16.013</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="1005">
                <text>Journal of Preventive Medicine and Public Health</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
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              <elementText elementTextId="1006">
                <text>Korean Society for Preventive Medicine</text>
              </elementText>
            </elementTextContainer>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Public aspects of medicine, Medicine</text>
              </elementText>
            </elementTextContainer>
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            <description>A language of the resource</description>
            <elementTextContainer>
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                <text>EN</text>
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  <item itemId="107" public="1" featured="0">
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              <name>Title</name>
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                  <text>Coronavirus</text>
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              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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        <name>Dublin Core</name>
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          <element elementId="50">
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              <elementText elementTextId="1009">
                <text>Inhibition of enterovirus 71 (EV-71) infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.</text>
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          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1010">
                <text>Chee Wah Tan, Yoke-Fun Chan, Kooi Mow Sim, Eng Lee Tan, Chit Laa Poh</text>
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          <element elementId="41">
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            <description>An account of the resource</description>
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              <elementText elementTextId="1011">
                <text>Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50) values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1012">
                <text>2012</text>
              </elementText>
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                <text>Pentamers not found in the universal proteome can enhance antigen specific immune responses and adjuvant vaccines.</text>
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                <text>Ami Patel, Jessica C Dong, Brett Trost, Jason S Richardson, Sarah Tohme, Shawn Babiuk, Anthony Kusalik, Sam K.P. Kung, Gary P. Kobinger</text>
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                <text>Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.</text>
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                <text>DOI: 10.1371/journal.pone.0043802</text>
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