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                  <text>Dominio científico: Coronavirus</text>
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                <text>Epigenetic Landscape during Coronavirus Infection</text>
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                <text>Alexandra Schäfer, Ralph S. Baric</text>
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                <text>Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.</text>
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                <text>coronaviruses, epigenetics, Systems Biology</text>
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                <text>DOI: 10.3390/pathogens6010008</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins</text>
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                <text>Beth N. Licitra, Gerald E. Duhamel, Gary R. Whittaker</text>
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                <text>Canine enteric coronavirus (CCoV) is an alphacoronavirus infecting dogs that is closely related to enteric coronaviruses of cats and pigs. While CCoV has traditionally caused mild gastro-intestinal clinical signs, there are increasing reports of lethal CCoV infections in dogs, with evidence of both gastrointestinal and systemic viral dissemination. Consequently, CCoV is now considered to be an emerging infectious disease of dogs. In addition to the two known serotypes of CCoV, novel recombinant variants of CCoV have been found containing spike protein N-terminal domains (NTDs) that are closely related  to those of feline and porcine strains. The increase in disease severity in dogs and the emergence of novel CCoVs can be attributed to the high level of recombination within the spike gene that can occur during infection by more than one CCoV type in the same host.</text>
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                <text>canine coronavirus, viral pathogenesis, spike protein, recombination</text>
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                <text>DOI: 10.3390/v6083363</text>
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                <text>Viruses</text>
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                <text>Microbiology</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>A Review of Novel Coronavirus, cause of Middle East Respiratory Syndrome</text>
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                <text>Katayoun Vahdat, Azam Amini, Akram Najafi, Mohammad Javad Haeri‌nejad</text>
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                <text>Abstract Background: Isolation of a novel virus belonging to coronavirdae family in September 2012, from patients in Middle East who had died of an acute respiratory illness &amp; renal failure lead to researches on this new virus. Here, a brief review to summarize the events of scientific findings of this new emerging virus. Material and Methods: This review is based on a comprehensive search of three databases (Pubmed, Embase and Cochrane) and WHO reports. The searched keywords were new coronavirus, Middle East, acute respieratory distress syndrom &amp; Saudi Arabia. Results: Due to novelty of virus only limited papers exist on searched databases, so only 50 papers were identified which after omitting repeated case reports, papers related to SARS and updated WHO reports, 30 papers were finally reviewed. Conclusion: WHO recommendation is evaluation of all patients with acute respiratory illness and history of travel to Saudi Arabia or other countries where this novel virus is epidemic.</text>
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                <text>2014</text>
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                <text>Acute Respirototy Distress Syndrom -  Middle East - New coronavirus- Saudi Arabia</text>
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                <text>DOI: </text>
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            <description>A related resource from which the described resource is derived</description>
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                <text>Iranian South Medical Journal</text>
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                <text>Bushehr University of Medical Sciences</text>
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                <text>Medicine (General)</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>How conserved are the conserved 16S-rRNA regions?</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Marcel Martinez-Porchas, Enrique Villalpando-Canchola, Luis Enrique Ortiz Suarez, Francisco Vargas-Albores</text>
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                <text>The 16S rRNA gene has been used as master key for studying prokaryotic diversity in almost every environment. Despite the claim of several researchers to have the best universal primers, the reality is that no primer has been demonstrated to be truly universal. This suggests that conserved regions of the gene may not be as conserved as expected. The aim of this study was to evaluate the conservation degree of the so-called conserved regions flanking the hypervariable regions of the 16S rRNA gene. Data contained in SILVA database (release 123) were used for the study. Primers reported as matches of each conserved region were assembled to form contigs; sequences sizing 12 nucleotides (12-mers) were extracted from these contigs and searched into the entire set of SILVA sequences. Frequency analysis shown that extreme regions, 1 and 10, registered the lowest frequencies. 12-mer frequencies revealed segments of contigs that were not as conserved as expected (≤90%). Fragments corresponding to the primer contigs 3, 4, 5b and 6a were recovered from all sequences in SILVA database. Nucleotide frequency analysis in each consensus demonstrated that only a small fraction of these so-called conserved regions is truly conserved in non-redundant sequences. It could be concluded that conserved regions of the 16S rRNA gene exhibit considerable variation that has to be considered when using this gene as biomarker.</text>
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                <text>2017</text>
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                <text>Kmers, Biodiversity, Conserved regions 16S, Primer design</text>
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                <text>DOI: 10.7717/peerj.3036</text>
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                <text>PeerJ Inc.</text>
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      <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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            <description>A name given to the resource</description>
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                <text>Epidemiology of severe acute respiratory syndrome Hospital Santa Cruz / RS - Brazil</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Marcelo Carneiro</text>
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            <description>An account of the resource</description>
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                <text>.</text>
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                <text>2013</text>
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                <text>DOI: 10.17058/reci.v3i2.3999</text>
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            <description>A related resource from which the described resource is derived</description>
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                <text>Revista de Epidemiologia e Controle de Infecção</text>
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                <text>Universidade de Santa Cruz do Sul</text>
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                <text>Internal medicine, Infectious and parasitic diseases, Medicine</text>
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            <description>A language of the resource</description>
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                <text>PT</text>
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              <name>Title</name>
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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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                  <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>
        <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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            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Anna Lundin, Ronald Dijkman, Tomas Bergström, Nina Kann, Beata Adamiak, Charles Hannoun, Eveline Kindler, Hulda  R. Jonsdottir, Doreen Muth, Joeri Kint, Maria Forlenza, Marcel A. Müller, Christian Drosten, Volker Thiel, Edward Trybala</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="4306">
                <text>Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.</text>
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                <text>2014</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="4308">
                <text>DOI: 10.1371/journal.ppat.1004166</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="4309">
                <text>PLoS Pathogens</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="4310">
                <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="4311">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
            </elementTextContainer>
          </element>
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            <name>Language</name>
            <description>A language of the resource</description>
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              <elementText elementTextId="4312">
                <text>EN</text>
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              <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>
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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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      <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>
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                <text>Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4296">
                <text>Yu Chen, Ceyang Su, Min Ke, Xu Jin, Lirong Xu, Zhou Zhang, Andong Wu, Ying Sun, Zhouning Yang, Po Tien, Tero Ahola, Yi Liang, Xinqi Liu, Deyin Guo</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="4297">
                <text>The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.</text>
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            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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                <text>2011</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="4299">
                <text>DOI: 10.1371/journal.ppat.1002294</text>
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            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="4300">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="4301">
                <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="4302">
                <text>Biology (General), Immunologic diseases. Allergy</text>
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            </elementTextContainer>
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            <name>Language</name>
            <description>A language of the resource</description>
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              <elementText elementTextId="4303">
                <text>EN</text>
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        <src>https://www.socictopen.socict.org/files/original/1452088d5192b6f01cfe06ca51cd8245.pdf</src>
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          <name>Dublin Core</name>
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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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>
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              </elementTextContainer>
            </element>
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    <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>
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        <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>
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                <text>Anatomy of the epidemiological literature on the 2003 SARS outbreaks in Hong Kong and Toronto: a time-stratified review.</text>
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            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4287">
                <text>Weijia Xing, Gilles Hejblum, Gabriel M. Leung, Alain-Jacques Valleron</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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                <text>BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p</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>
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                <text>2010</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="4290">
                <text>DOI: 10.1371/journal.pmed.1000272</text>
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            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="4291">
                <text>PLoS Medicine</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="4292">
                <text>Public Library of Science (PLoS)</text>
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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>Medicine</text>
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            <name>Language</name>
            <description>A language of the resource</description>
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                <text>EN</text>
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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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                  <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>
        <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>
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              <elementText elementTextId="4277">
                <text>Enhanced regulatory sequence prediction using gapped k-mer features.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4278">
                <text>Mahmoud Ghandi, Dong Won Lee, Morteza Mohammad-Noori, Michael A Beer</text>
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          <element elementId="41">
            <name>Description</name>
            <description>An account of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4279">
                <text>Oligomers of length k, or k-mers, are convenient and widely used features for modeling the properties and functions of DNA and protein sequences. However, k-mers suffer from the inherent limitation that if the parameter k is increased to resolve longer features, the probability of observing any specific k-mer becomes very small, and k-mer counts approach a binary variable, with most k-mers absent and a few present once. Thus, any statistical learning approach using k-mers as features becomes susceptible to noisy training set k-mer frequencies once k becomes large. To address this problem, we introduce alternative feature sets using gapped k-mers, a new classifier, gkm-SVM, and a general method for robust estimation of k-mer frequencies. To make the method applicable to large-scale genome wide applications, we develop an efficient tree data structure for computing the kernel matrix. We show that compared to our original kmer-SVM and alternative approaches, our gkm-SVM predicts functional genomic regulatory elements and tissue specific enhancers with significantly improved accuracy, increasing the precision by up to a factor of two. We then show that gkm-SVM consistently outperforms kmer-SVM on human ENCODE ChIP-seq datasets, and further demonstrate the general utility of our method using a Naïve-Bayes classifier. Although developed for regulatory sequence analysis, these methods can be applied to any sequence classification problem.</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>
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                <text>2014</text>
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            </elementTextContainer>
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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="4281">
                <text>DOI: 10.1371/journal.pcbi.1003711</text>
              </elementText>
            </elementTextContainer>
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                <text>Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.</text>
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                <text>DOI: 10.1371/journal.pmed.0030027</text>
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                <text>PLoS Medicine</text>
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