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Sample records for sars coronavirus synergy

  1. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

    NARCIS (Netherlands)

    ter Meulen, Jan; Bakker, Alexander B. H.; van den Brink, Edward N.; Weverling, Gerrit J.; Martina, Byron E. E.; Haagmans, Bart L.; Kuiken, Thijs; de Kruif, John; Preiser, Wolfgang; Spaan, Willy; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

    2004-01-01

    SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal

  2. An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-Reactivity with SARS Coronavirus

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    David M Patrick

    2006-01-01

    Full Text Available BACKGROUND: In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV.

  3. Bioinformatics analysis of SARS coronavirus genome polymorphism

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    Pavlović-Lažetić Gordana M

    2004-05-01

    Full Text Available Abstract Background We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP, insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. Results The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with "regular" isolates (no insertions / deletions except for 5' and 3' ends, the B-group of isolates with "long insertions", and the C-group of isolates with "many individual" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH. The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones. Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. Conclusions The comparative study of SARS-CoV isolates provides essential information for genome

  4. The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.

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    Susanne Pfefferle

    2011-10-01

    Full Text Available Coronaviruses (CoVs are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS in 2002/2003 has demonstrated human vulnerability to (Coronavirus CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B as interaction partners of the CoV non-structural protein 1 (Nsp1. These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.

  5. Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum

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    K.-Y. Hwa

    2008-01-01

    Full Text Available Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV. The spike (S protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937 and D08 (residues 942–951 were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502 stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.

  6. About Coronavirus

    Science.gov (United States)

    ... Coronaviruses Symptoms and Diagnosis Transmission Prevention and Treatment Human Coronavirus Types SARS-CoV MERS-CoV Resources and References About Coronaviruses Recommend on Facebook Tweet Share Compartir Symptoms and Diagnosis Lists illnesses ...

  7. Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology

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    Blom Nikolaj

    2004-06-01

    Full Text Available Abstract Background Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS, efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR, transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Conclusions Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: http://www.cbs.dtu.dk/services/NetCorona/.

  8. Reverse genetics of SARS-related coronavirus using vaccinia virus-based recombination.

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    Sjoerd H E van den Worm

    Full Text Available Severe acute respiratory syndrome (SARS is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV. Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs. In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E. Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.

  9. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.

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    Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A; Zhu, Guangjian; Epstein, Jonathan H; Mazet, Jonna K; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li

    2013-11-28

    The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

  10. The SARS-unique domain (SUD of SARS coronavirus contains two macrodomains that bind G-quadruplexes.

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    Jinzhi Tan

    2009-05-01

    Full Text Available Since the outbreak of severe acute respiratory syndrome (SARS in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV, the non-structural proteins (Nsps, have been determined. However, within the large Nsp3 (1922 amino-acid residues, the structure and function of the so-called SARS-unique domain (SUD have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 ("SUD(core" of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 A resolution, respectively revealed that SUD(core forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 3'-nontranslated regions of mRNAs coding for certain host-cell proteins

  11. Excretion and detection of SARS coronavirus and its nucleic acid from digestive system

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    Wang, Xin-Wei; Li, Jin-Song; Guo, Ting-Kai; Zhen, Bei; Kong, Qing-Xin; Yi, Bin; Li, Zhong; Song, Nong; Jin, Min; Wu, Xiao-Ming; Xiao, Wen-Jun; Zhu, Xiu-Mei; Gu, Chang-Qing; Yin, Jing; Wei, Wei; Yao, Wei; Liu, Chao; Li, Jian-Feng; Ou, Guo-Rong; Wang, Min-Nian; Fang, Tong-Yu; Wang, Gui-Jie; Qiu, Yao-Hui; Wu, Huai-Huan; Chao, Fu-Huan; Li, Jun-Wen

    2005-01-01

    AIM: To study whether severe acute respiratory syndrome coronavirus (SARS-CoV) could be excreted from digestive system. METHODS: Cell culture and semi-nested RT-PCR were used to detect SARS-CoV and its RNA from 21 stool and urine samples, and a kind of electropositive filter media particles was used to concentrate the virus in 10 sewage samples from two hospitals receiving SARS patients in Beijing in China. RESULTS: It was demonstrated that there was no live SARS-CoV in all samples collected, but the RNA of SARS-CoV could be detected in seven stool samples from SARS patients with any one of the symptoms of fever, malaise, cough, or dyspnea, in 10 sewage samples before disinfection and 3 samples after disinfection from the two hospitals. The RNA could not be detected in urine and stool samples from patients recovered from SARS. CONCLUSION: Nucleic acid of SARS-CoV can be excreted through the stool of patients into sewage system, and the possibility of SARS-CoV transmitting through digestive system cannot be excluded. PMID:16038039

  12. The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus

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    McDermott, Jason E.; Mitchell, Hugh D.; Gralinski, Lisa E.; Eisfeld, Amie J.; Josset, Laurence; Bankhead, Armand; Neumann, Gabriele; Tilton, Susan C.; Schäfer, Alexandra; Li, Chengjun; Fan, Shufang; McWeeney, Shannon; Baric, Ralph S.; Katze, Michael G.; Waters, Katrina M.

    2016-09-23

    The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ antiimmune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine, tumor necrosis factor alpha (TNFα), promote pathogenesis through a parallel feed-forward circuit that promotes inflammation. These results are consistent with previous studies showing the role of over-stimulation of the inflammatory response to SARS-CoV in pathogenesis. We conclude that the critical balance between immune response and inflammation can be manipulated to improve the outcome of the infection. Further, our study provides two potential therapeutic strategies for mitigating the effects of SARS-CoV infection, and may provide insight into treatment strategies for Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

  13. Automated extraction protocol for quantification of SARS-Coronavirus RNA in serum: an evaluation study

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    Lui Wing-bong

    2006-02-01

    Full Text Available Abstract Background We have previously developed a test for the diagnosis and prognostic assessment of the severe acute respiratory syndrome (SARS based on the detection of the SARS-coronavirus RNA in serum by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR. In this study, we evaluated the feasibility of automating the serum RNA extraction procedure in order to increase the throughput of the assay. Methods An automated nucleic acid extraction platform using the MagNA Pure LC instrument (Roche Diagnostics was evaluated. We developed a modified protocol in compliance with the recommended biosafety guidelines from the World Health Organization based on the use of the MagNA Pure total nucleic acid large volume isolation kit for the extraction of SARS-coronavirus RNA. The modified protocol was compared with a column-based extraction kit (QIAamp viral RNA mini kit, Qiagen for quantitative performance, analytical sensitivity and precision. Results The newly developed automated protocol was shown to be free from carry-over contamination and have comparable performance with other standard protocols and kits designed for the MagNA Pure LC instrument. However, the automated method was found to be less sensitive, less precise and led to consistently lower serum SARS-coronavirus concentrations when compared with the column-based extraction method. Conclusion As the diagnostic efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is critically associated with the analytical sensitivity and quantitative performance contributed both by the RNA extraction and RT-PCR components of the test, we recommend the use of the column-based manual RNA extraction method.

  14. Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

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    Zhao Ping; Cao Jie; Zhao Lanjuan; Qin Zhaolin; Ke Jinshan; Pan Wei; Ren Hao; Yu Jianguo; Qi Zhongtian

    2005-01-01

    The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5α and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobulins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD8 + CTL responses to N protein. The study shows that N protein of SARS-CoV not only is an important B cell immunogen, but also can elicit broad-based cellular immune responses. The results indicate that the N protein may be of potential value in vaccine development for specific prophylaxis and treatment against SARS

  15. Crystallization and diffraction analysis of the SARS coronavirus nsp10–nsp16 complex

    International Nuclear Information System (INIS)

    Debarnot, Claire; Imbert, Isabelle; Ferron, François; Gluais, Laure; Varlet, Isabelle; Papageorgiou, Nicolas; Bouvet, Mickaël; Lescar, Julien; Decroly, Etienne; Canard, Bruno

    2011-01-01

    The expression, purification and crystallization of the SARS coronavirus nsp16 RNA-cap AdoMet-dependent (nucleoside-2′O)-methyltransferase in complex with its activating factor nsp10 are reported. To date, the SARS coronavirus is the only known highly pathogenic human coronavirus. In 2003, it was responsible for a large outbreak associated with a 10% fatality rate. This positive RNA virus encodes a large replicase polyprotein made up of 16 gene products (nsp1–16), amongst which two methyltransferases, nsp14 and nsp16, are involved in viral mRNA cap formation. The crystal structure of nsp16 is unknown. Nsp16 is an RNA-cap AdoMet-dependent (nucleoside-2′-O-)-methyltransferase that is only active in the presence of nsp10. In this paper, the expression, purification and crystallization of nsp10 in complex with nsp16 are reported. The crystals diffracted to a resolution of 1.9 Å resolution and crystal structure determination is in progress

  16. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.

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    Kèvin Knoops

    2008-09-01

    Full Text Available Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV, replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200-300 nm, and "vesicle packets" apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this "replication network" will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.

  17. Dynamics of SARS-coronavirus HR2 domain in the prefusion and transition states

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    McReynolds, Susanna; Jiang, Shaokai; Rong, Lijun; Caffrey, Michael

    2009-12-01

    The envelope glycoproteins S1 and S2 of severe acute respiratory syndrome coronavirus (SARS-CoV) mediate viral entry by conformational change from a prefusion state to a postfusion state that enables fusion of the viral and target membranes. In this work we present the characterization of the dynamic properties of the SARS-CoV S2-HR2 domain (residues 1141-1193 of S) in the prefusion and newly discovered transition states by NMR 15N relaxation studies. The dynamic properties of the different states, which are stabilized under different experimental conditions, extend the current model of viral membrane fusion and give insight into the design of structure-based antagonists of SARS-CoV in particular, as well as other enveloped viruses such as HIV.

  18. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

    International Nuclear Information System (INIS)

    Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian

    2007-01-01

    The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection

  19. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.

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    Anjeanette Roberts

    2007-01-01

    Full Text Available No single animal model for severe acute respiratory syndrome (SARS reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15 that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15, duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as

  20. Structure and inhibition of the SARS coronavirus envelope protein ion channel.

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    Konstantin Pervushin

    2009-07-01

    Full Text Available The envelope (E protein from coronaviruses is a small polypeptide that contains at least one alpha-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA, but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV that the transmembrane domain of E protein (ETM forms pentameric alpha-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular alpha-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293 cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA, but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.

  1. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

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    I-Chueh Huang

    2011-01-01

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  2. Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS coronavirus

    International Nuclear Information System (INIS)

    Ricagno, Stéfano; Coutard, Bruno; Grisel, Sacha; Brémond, Nicolas; Dalle, Karen; Tocque, Fabienne; Campanacci, Valérie; Lichière, Julie; Lantez, Violaine; Debarnot, Claire; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre

    2006-01-01

    Crystals of Nsp15 from the aetiological agent of SARS have been grown at room temperature. Crystals have cubic symmetry and diffract to a maximum resolution of 2.7 Å. The non-structural protein Nsp15 from the aetiological agent of SARS (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. This enzyme plays an essential role in viral replication and transcription since a mutation in the related H229E human coronavirus nsp15 gene can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has been cloned and expressed in Escherichia coli with an N-terminal hexahistidine tag and has been purified to homogeneity. The protein was subsequently crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of the apoenzyme were obtained from 100 nl nanodrops. They belong to space group P4 1 32 or P4 3 32, with unit-cell parameters a = b = c = 166.8 Å. Diffraction data were collected to a maximum resolution of 2.7 Å

  3. Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS coronavirus

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    Ricagno, Stéfano; Coutard, Bruno; Grisel, Sacha; Brémond, Nicolas; Dalle, Karen; Tocque, Fabienne; Campanacci, Valérie; Lichière, Julie; Lantez, Violaine; Debarnot, Claire; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre, E-mail: marie-pierre.egloff@afmb.univ-mrs.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, Ecole Supérieure d’Ingénieurs de Luminy-Case 925, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

    2006-04-01

    Crystals of Nsp15 from the aetiological agent of SARS have been grown at room temperature. Crystals have cubic symmetry and diffract to a maximum resolution of 2.7 Å. The non-structural protein Nsp15 from the aetiological agent of SARS (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. This enzyme plays an essential role in viral replication and transcription since a mutation in the related H229E human coronavirus nsp15 gene can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has been cloned and expressed in Escherichia coli with an N-terminal hexahistidine tag and has been purified to homogeneity. The protein was subsequently crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of the apoenzyme were obtained from 100 nl nanodrops. They belong to space group P4{sub 1}32 or P4{sub 3}32, with unit-cell parameters a = b = c = 166.8 Å. Diffraction data were collected to a maximum resolution of 2.7 Å.

  4. SARS-Coronavirus ancestor's foot-prints in South-East Asian bat colonies and the refuge theory.

    Science.gov (United States)

    Gouilh, Meriadeg Ar; Puechmaille, Sébastien J; Gonzalez, Jean-Paul; Teeling, Emma; Kittayapong, Pattamaporn; Manuguerra, Jean-Claude

    2011-10-01

    One of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. In the case of the emergence of SevereAcute Respiratory Syndrome Coronavirus (SARS-CoV), several studies have shown coronavirus diversity in bats as well as the existence of SARS-CoV infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. To elucidate the biogeographic origin of SARS-CoV and investigate the role that bats played in its emergence, we amplified coronavirus sequences from bat species captured throughout Thailand and assessed the phylogenetic relationships to each other and to other published coronavirus sequences. To this end, RdRp sequence of Coronavirinae was targeted by RT-PCR in non-invasive samples from bats collected in Thailand. Two new coronaviruses were detected in two bat species: one Betacoronavirus in Hipposideros larvatus and one Alphacoronavirus in Hipposiderosarmiger. Interestingly, these viruses from South-East Asia are related to those previously detected in Africa (Betacoronavirus-b) or in Europe (Alphacoronavirus & Betacoronavirus-b). These findings illuminate the origin and the evolutionary history of the SARS-CoV group found in bats by pushing forward the hypothesis of a Betacoronavirus spill-over from Hipposideridae to Rhinolophidae and then from Rhinolophidae to civets and Human. All reported Betacoronaviruses-b (SARS-CoV group) of Hipposideridae and Rhinolophidae respectively cluster in two groups despite their broad geographic distribution and the sympatry of their hosts, which is in favor of an ancient and genetically independent evolution of Betacoronavirus-b clusters in these families. Moreover, despite its probable pathogenicity, we found that a Betacoronavirus-b can persistently infect a medium-sized hipposiderid bat colony. These findings illustrate the importance of the host

  5. Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.

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    Jean Kaoru Millet

    Full Text Available BACKGROUND: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S. There are still many unknowns on the implication of cellular factors that regulate the entry process. METHODOLOGY/PRINCIPAL FINDINGS: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion. CONCLUSIONS/SIGNIFICANCE: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.

  6. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

    Science.gov (United States)

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-12-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.'' Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Analysis of intraviral protein-protein interactions of the SARS coronavirus ORFeome.

    Directory of Open Access Journals (Sweden)

    Albrecht von Brunn

    2007-05-01

    Full Text Available The severe acute respiratory syndrome coronavirus (SARS-CoV genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies.

  8. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

    Directory of Open Access Journals (Sweden)

    Weber Friedemann

    2006-03-01

    Full Text Available Abstract Background SARS coronavirus (SARS-CoV is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. Results A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. Conclusion Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

  9. Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge

    Directory of Open Access Journals (Sweden)

    Chen Liangan

    2005-01-01

    Full Text Available Abstract Objective The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. Methods The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [DLCO] Findings Of all the subjects, 81.2% (311 of 383 patients tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients were suffering from lung diffusion abnormities (DLCO Interpretation The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.

  10. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1

    Science.gov (United States)

    Ma-Lauer, Yue; Carbajo-Lozoya, Javier; Müller, Marcel A.; Deng, Wen; Lei, Jian; Meyer, Benjamin; Kusov, Yuri; von Brunn, Brigitte; Bairad, Dev Raj; Hünten, Sabine; Drosten, Christian; Hermeking, Heiko; Leonhardt, Heinrich; Mann, Matthias; Hilgenfeld, Rolf; von Brunn, Albrecht

    2016-01-01

    Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PLpro), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PLpros from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PLpro fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PLpro alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes. PMID:27519799

  11. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

    Directory of Open Access Journals (Sweden)

    Taisheng Li

    2006-12-01

    Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

  12. Identification of a new human coronavirus

    NARCIS (Netherlands)

    van der Hoek, Lia; Pyrc, Krzysztof; Jebbink, Maarten F.; Vermeulen-Oost, Wilma; Berkhout, Ron J. M.; Wolthers, Katja C.; Wertheim-van Dillen, Pauline M. E.; Kaandorp, Jos; Spaargaren, Joke; Berkhout, Ben

    2004-01-01

    Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus was

  13. The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein

    International Nuclear Information System (INIS)

    Kumar, Purnima; Gunalan, Vithiagaran; Liu Boping; Chow, Vincent T.K.; Druce, Julian; Birch, Chris; Catton, Mike; Fielding, Burtram C.; Tan, Yee-Joo; Lal, Sunil K.

    2007-01-01

    Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a severe outbreak in several regions of the world in 2003. The SARS-CoV genome is predicted to contain 14 functional open reading frames (ORFs). The first ORF (1a and 1b) encodes a large polyprotein that is cleaved into nonstructural proteins (nsp). The other ORFs encode for four structural proteins (spike, membrane, nucleocapsid and envelope) as well as eight SARS-CoV-specific accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b and 9b). In this report we have cloned the predicted nsp8 gene and the ORF6 gene of the SARS-CoV and studied their abilities to interact with each other. We expressed the two proteins as fusion proteins in the yeast two-hybrid system to demonstrate protein-protein interactions and tested the same using a yeast genetic cross. Further the strength of the interaction was measured by challenging growth of the positive interaction clones on increasing gradients of 2-amino trizole. The interaction was then verified by expressing both proteins separately in-vitro in a coupled-transcription translation system and by coimmunoprecipitation in mammalian cells. Finally, colocalization experiments were performed in SARS-CoV infected Vero E6 mammalian cells to confirm the nsp8-ORF6 interaction. To the best of our knowledge, this is the first report of the interaction between a SARS-CoV accessory protein and nsp8 and our findings suggest that ORF6 protein may play a role in virus replication

  14. Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501

    DEFF Research Database (Denmark)

    Røder, Gustav; Kristensen, Ole; Kastrup, Jette S

    2008-01-01

    , the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) has been determined at high resolution (1.87 A). The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making...

  15. HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

    International Nuclear Information System (INIS)

    Tsao, Y.-P.; Lin, J.-Y.; Jan, J.-T.; Leng, C.-H.; Chu, C.-C.; Yang, Y.-C.; Chen, S.-L.

    2006-01-01

    The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be First identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-γ stimulation of blood CD8 + T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS

  16. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion

    International Nuclear Information System (INIS)

    Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R.

    2009-01-01

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.

  17. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

    Directory of Open Access Journals (Sweden)

    Jianhua Sui

    2008-11-01

    Full Text Available Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S protein of animal and human SARS coronaviruses (SARS-CoVs during and between two zoonotic transfers (2002/03 and 2003/04 are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID "hot spot" in a light chain CDR (complementarity determining region alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural

  18. The Severe Acute Respiratory Syndrome (SARS-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein

    Directory of Open Access Journals (Sweden)

    Tan Yee-Joo

    2005-02-01

    Full Text Available Abstract Background A recent publication reported that a tyrosine-dependent sorting signal, present in cytoplasmic tail of the spike protein of most coronaviruses, mediates the intracellular retention of the spike protein. This motif is missing from the spike protein of the severe acute respiratory syndrome-coronavirus (SARS-CoV, resulting in high level of surface expression of the spike protein when it is expressed on its own in vitro. Presentation of the hypothesis It has been shown that the severe acute respiratory syndrome-coronavirus genome contains open reading frames that encode for proteins with no homologue in other coronaviruses. One of them is the 3a protein, which is expressed during infection in vitro and in vivo. The 3a protein, which contains a tyrosine-dependent sorting signal in its cytoplasmic domain, is expressed on the cell surface and can undergo internalization. In addition, 3a can bind to the spike protein and through this interaction, it may be able to cause the spike protein to become internalized, resulting in a decrease in its surface expression. Testing the hypothesis The effects of 3a on the internalization of cell surface spike protein can be examined biochemically and the significance of the interplay between these two viral proteins during viral infection can be studied using reverse genetics methodology. Implication of the hypothesis If this hypothesis is proven, it will indicate that the severe acute respiratory syndrome-coronavirus modulates the surface expression of the spike protein via a different mechanism from other coronaviruses. The interaction between 3a and S, which are expressed from separate subgenomic RNA, would be important for controlling the trafficking properties of S. The cell surface expression of S in infected cells significantly impacts viral assembly, viral spread and viral pathogenesis. Modulation by this unique pathway could confer certain advantages during the replication of the severe

  19. Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups

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    He Shao-Heng

    2006-10-01

    Full Text Available Abstract Background It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS coronavirus (CoV is the cause of the SARS outbreak worldwide. The spike (S protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. Results By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163 in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24% of positively selected sites was located in receptor-binding domain (RBD than in heptad repeat (HR1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208, and a greater percentage (25% of these sites occurred in HR1–HR2 region than in RBD in 03-early

  20. Selection of SARS-Coronavirus-specific B cell epitopes by phage peptide library screening and evaluation of the immunological effect of epitope-based peptides on mice

    International Nuclear Information System (INIS)

    Yu Hua; Jiang Lifang; Fang Danyun; Yan Huijun; Zhou Jingjiao; Zhou Junmei; Liang Yu; Gao Yang; Zhao, Wei; Long Beiguo

    2007-01-01

    Antibodies to SARS-Coronavirus (SARS-CoV)-specific B cell epitopes might recognize the pathogen and interrupt its adherence to and penetration of host cells. Hence, these epitopes could be useful for diagnosis and as vaccine constituents. Using the phage-displayed peptide library screening method and purified Fab fragments of immunoglobulin G (IgG Fab) from normal human sera and convalescent sera from SARS-CoV-infected patients as targets, 11 B cell epitopes of SARS-CoV spike glycoprotein (S protein) and membrane protein (M protein) were screened. After a bioinformatics tool was used to analyze these epitopes, four epitope-based S protein dodecapeptides corresponding to the predominant epitopes were chosen for synthesis. Their antigenic specificities and immunogenicities were studied in vitro and in vivo. Flow cytometry and ELISPOT analysis of lymphocytes as well as a serologic analysis of antibody showed that these peptides could trigger a rapid, highly effective, and relatively safe immune response in BALB/c mice. These findings might aid development of SARS diagnostics and vaccines. Moreover, the role of S and M proteins as important surface antigens is confirmed

  1. Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion

    International Nuclear Information System (INIS)

    Petit, Chad M.; Melancon, Jeffrey M.; Chouljenko, Vladimir N.; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

    2005-01-01

    The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion

  2. False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid Enzyme-Linked Immunosorbent Assay Due to HCoV-OC43 and HCoV-229E Rectified by Western Blotting with Recombinant SARS-CoV Spike Polypeptide

    OpenAIRE

    Woo, Patrick C. Y.; Lau, Susanna K. P.; Wong, Beatrice H. L.; Chan, Kwok-Hung; Hui, Wai-Ting; Kwan, Grace S. W.; Peiris, J. S. Malik; Couch, Robert B.; Yuen, Kwok-Yung

    2004-01-01

    Using paired serum samples obtained from patients with illness associated with increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in anti...

  3. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

  4. Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion

    International Nuclear Information System (INIS)

    Petit, Chad M.; Chouljenko, Vladimir N.; Iyer, Arun; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

    2007-01-01

    The SARS-coronavirus (SARS-CoV) is the etiological agent of the severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. The cytoplasmic portion of the S glycoprotein contains four cysteine-rich amino acid clusters. Individual cysteine clusters were altered via cysteine-to-alanine amino acid replacement and the modified S glycoproteins were tested for their transport to cell-surfaces and ability to cause cell fusion in transient transfection assays. Mutagenesis of the cysteine cluster I, located immediately proximal to the predicted transmembrane, domain did not appreciably reduce cell-surface expression, although S-mediated cell fusion was reduced by more than 50% in comparison to the wild-type S. Similarly, mutagenesis of the cysteine cluster II located adjacent to cluster I reduced S-mediated cell fusion by more than 60% compared to the wild-type S, while cell-surface expression was reduced by less than 20%. Mutagenesis of cysteine clusters III and IV did not appreciably affect S cell-surface expression or S-mediated cell fusion. The wild-type S was palmitoylated as evidenced by the efficient incorporation of 3 H-palmitic acid in wild-type S molecules. S glycoprotein palmitoylation was significantly reduced for mutant glycoproteins having cluster I and II cysteine changes, but was largely unaffected for cysteine cluster III and IV mutants. These results show that the S cytoplasmic domain is palmitoylated and that palmitoylation of the membrane proximal cysteine clusters I and II may be important for S-mediated cell fusion

  5. A study on antigenicity and receptor-binding ability of fragment 450-650 of the spike protein of SARS coronavirus

    International Nuclear Information System (INIS)

    Zhao Jincun; Wang Wei; Yuan Zhihong; Jia Rujing; Zhao Zhendong; Xu Xiaojun; Lv Ping; Zhang Yan; Jiang Chengyu; Gao Xiaoming

    2007-01-01

    The spike (S) protein of SARS coronavirus (SARS-CoV) is responsible for viral binding with ACE2 molecules. Its receptor-binding motif (S-RBM) is located between residues 424 and 494, which folds into 2 anti-parallel β-sheets, β5 and β6. We have previously demonstrated that fragment 450-650 of the S protein (S450-650) is predominantly recognized by convalescent sera of SARS patients. The N-terminal 60 residues (450-510) of the S450-650 fragment covers the entire β6 strand of S-RBM. In the present study, we demonstrate that patient sera predominantly recognized 2 linear epitopes outside the β6 fragment, while the mouse antisera, induced by immunization of BALB/c mice with recombinant S450-650, mainly recognized the β6 strand-containing region. Unlike patient sera, however, the mouse antisera were unable to inhibit the infectivity of S protein-expressing (SARS-CoV-S) pseudovirus. Fusion protein between green fluorescence protein (GFP) and S450-650 (S450-650-GFP) was able to stain Vero E6 cells and deletion of the β6 fragment rendered the fusion product (S511-650-GFP) unable to do so. Similarly, recombinant S450-650, but not S511-650, was able to block the infection of Vero E6 cells by the SARS-CoV-S pseudovirus. Co-precipitation experiments confirmed that S450-650 was able to specifically bind with ACE2 molecules in lysate of Vero E6 cells. However, the ability of S450-510, either alone or in fusion with GFP, to bind with ACE2 was significantly poorer compared with S450-650. Our data suggest a possibility that, although the β6 strand alone is able to bind with ACE2 with relatively high affinity, residues outside the S-RBM could also assist the receptor binding of SARS-CoV-S protein

  6. Solution structure of the c-terminal dimerization domain of SARS coronavirus nucleocapsid protein solved by the SAIL-NMR method.

    Science.gov (United States)

    Takeda, Mitsuhiro; Chang, Chung-ke; Ikeya, Teppei; Güntert, Peter; Chang, Yuan-hsiang; Hsu, Yen-lan; Huang, Tai-huang; Kainosho, Masatsune

    2008-07-18

    The C-terminal domain (CTD) of the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP) contains a potential RNA-binding region in its N-terminal portion and also serves as a dimerization domain by forming a homodimer with a molecular mass of 28 kDa. So far, the structure determination of the SARS-CoV NP CTD in solution has been impeded by the poor quality of NMR spectra, especially for aromatic resonances. We have recently developed the stereo-array isotope labeling (SAIL) method to overcome the size problem of NMR structure determination by utilizing a protein exclusively composed of stereo- and regio-specifically isotope-labeled amino acids. Here, we employed the SAIL method to determine the high-quality solution structure of the SARS-CoV NP CTD by NMR. The SAIL protein yielded less crowded and better resolved spectra than uniform (13)C and (15)N labeling, and enabled the homodimeric solution structure of this protein to be determined. The NMR structure is almost identical with the previously solved crystal structure, except for a disordered putative RNA-binding domain at the N-terminus. Studies of the chemical shift perturbations caused by the binding of single-stranded DNA and mutational analyses have identified the disordered region at the N-termini as the prime site for nucleic acid binding. In addition, residues in the beta-sheet region also showed significant perturbations. Mapping of the locations of these residues onto the helical model observed in the crystal revealed that these two regions are parts of the interior lining of the positively charged helical groove, supporting the hypothesis that the helical oligomer may form in solution.

  7. The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.

    Directory of Open Access Journals (Sweden)

    Rinki Minakshi

    2009-12-01

    Full Text Available The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR, which includes the inositol-requiring enzyme 1 (IRE-1, activating transcription factor 6 (ATF6 and PKR-like ER kinase (PERK pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1 increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha and inhibitory effects of a dominant-negative form of eIF2alpha on GRP78 promoter activity, (2 increased translation of activating transcription factor 4 (ATF4 mRNA, and (3 ATF4-dependent activation of the C/EBP homologous protein (CHOP gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1 degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.

  8. Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species.

    Science.gov (United States)

    Yu, Meng; Stevens, Vicky; Berry, Jody D; Crameri, Gary; McEachern, Jennifer; Tu, Changchun; Shi, Zhengli; Liang, Guodong; Weingartl, Hana; Cardosa, Jane; Eaton, Bryan T; Wang, Lin-Fa

    2008-02-29

    Knowledge of immunodominant regions in major viral antigens is important for rational design of effective vaccines and diagnostic tests. Although there have been many reports of such work done for SARS-CoV, these were mainly focused on the immune responses of humans and mice. In this study, we aim to search for and compare immunodominant regions of the spike (S) and nucleocapsid (N) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and horse. Twelve overlapping recombinant protein fragments were produced in Escherichia coli, six each for the S and N proteins, which covered the entire coding region of the two proteins. Using a membrane-strip based Western blot approach, the reactivity of each antigen fragment against a panel of animal sera was determined. Immunodominant regions containing linear epitopes, which reacted with sera from all the species tested, were identified for both proteins. The S3 fragment (aa 402-622) and the N4 fragment (aa 220-336) were the most immunodominant among the six S and N fragments, respectively. Antibodies raised against the S3 fragment were able to block the binding of a panel of S-specific monoclonal antibodies (mAb) to SARS-CoV in ELISA, further demonstrating the immunodominance of this region. Based on these findings, one-step competition ELISAs were established which were able to detect SARS-CoV antibodies from human and at least seven different animal species. Considering that a large number of animal species are known to be susceptible to SARS-CoV, these assays will be a useful tool to trace the origin and transmission of SARS-CoV and to minimise the risk of animal-to-human transmission.

  9. SYNERGY OF OPTICAL AND SAR DATA FOR MAPPING AND MONITORING MANGROVES

    Directory of Open Access Journals (Sweden)

    A. K. Monzon

    2016-06-01

    Full Text Available Quantitative information on mangrove cover extents is essential in producing relevant resource management plans and conservation strategies. In the Philippines, mangrove rehabilitation was made a priority in relation to disaster risk response and mitigation following the calamities in the coastal communities during typhoon Haiyan/Yolanda; hence, baseline information on the extent of remaining mangrove cover was essential for effective site interventions. Although mangrove cover maps for the country already exists, analysis of mangrove cover changes were limited to the application of fixed annual deforestation rates due to the challenge of acquiring consistent temporal cloud-free optical satellite data over large landscapes. This study presents an initial analysis of SAR and optical imagery combined with field-based observations for detecting mangrove cover extent and changes through a straightforward graphical approach. The analysis is part of a larger study evaluating the synergistic use of time-series L-band SAR and optical data for mapping and monitoring of mangroves. Image segmentation was implemented on the 25-meter ALOS/PALSAR image mosaics, in which the generated objects were subjected to statistical analysis using the software R. In combination with selected Landsat bands, the class statistics from the image bands were used to generate decision trees and thresholds for the hierarchical image classification. The results were compared with global mangrove cover dataset and validated using collected ground truth data. This study developed an integrated replicable approach for analyzing future radar and optical datasets, essential in national level mangrove cover change monitoring and assessment for long-term conservation targets and strategies.

  10. Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

    Science.gov (United States)

    Yount, Boyd; Roberts, Rhonda S.; Lindesmith, Lisa; Baric, Ralph S.

    2006-08-01

    Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses. regulation | systems biology | vaccine design

  11. The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis

    NARCIS (Netherlands)

    Bogaards, Johannes Antonie; Putter, Hein; Jan Weverling, Gerrit; ter Meulen, Jan; Goudsmit, Jaap

    2007-01-01

    BACKGROUND: Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that

  12. Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

    International Nuclear Information System (INIS)

    Chou, Te-hui W.; Wang, Shixia; Sakhatskyy, Pavlo V.; Mboudoudjeck, Innocent; Lawrence, John M.; Huang Song; Coley, Scott; Yang Baoan; Li Jiaming; Zhu Qingyu; Lu Shan

    2005-01-01

    Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV

  13. Feline and canine coronaviruses: common genetic and pathobiological features.

    Science.gov (United States)

    Le Poder, Sophie

    2011-01-01

    A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

  14. Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

    Directory of Open Access Journals (Sweden)

    Sophie Le Poder

    2011-01-01

    Full Text Available A new human coronavirus responsible for severe acute respiratory syndrome (SARS was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

  15. Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein

    International Nuclear Information System (INIS)

    Duquerroy, Stephane; Vigouroux, Armelle; Rottier, Peter J.M.; Rey, Felix A.; Jan Bosch, Berend

    2005-01-01

    The coronavirus spike glycoprotein is a class I membrane fusion protein with two characteristic heptad repeat regions (HR1 and HR2) in its ectodomain. Here, we report the X-ray structure of a previously characterized HR1/HR2 complex of the severe acute respiratory syndrome coronavirus spike protein. As expected, the HR1 and HR2 segments are organized in antiparallel orientations within a rod-like molecule. The HR1 helices form an exceptionally long (120 A) internal coiled coil stabilized by hydrophobic and polar interactions. A striking arrangement of conserved asparagine and glutamine residues of HR1 propagates from two central chloride ions, providing hydrogen-bonding 'zippers' that strongly constrain the path of the HR2 main chain, forcing it to adopt an extended conformation at either end of a short HR2 α-helix

  16. A molecular arms race between host innate antiviral response and emerging human coronaviruses.

    Science.gov (United States)

    Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

    2016-02-01

    Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

  17. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-01-01

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

  18. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin

    Science.gov (United States)

    Kumaki, Yohichi; Wandersee, Miles K.; Smith, Aaron J.; Zhou, Yanchen; Simmons, Graham; Nelson, Nathan M.; Bailey, Kevin W.; Vest, Zachary G.; Li, Joseph K.-K.; Chan, Paul Kay-Sheung; Smee, Donald F.; Barnard, Dale L.

    2011-01-01

    Urtica dioica agglutinin (UDA) is a small plant monomeric lectin, 8.7 kDa in size, with an N-acetylglucosamine specificity that inhibits viruses from Nidovirales in vitro. In the current study, we first examined the efficacy of UDA on the replication of different SARS-CoV strains in Vero 76 cells. UDA inhibited virus replication in a dose-dependent manner and reduced virus yields of the Urbani strain by 90% at 1.1 ± 0.4 µg/ml in Vero 76 cells. Then, UDA was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. BALB/c mice were infected with two LD50 (575 PFU) of virus for 4 hours before the mice were treated intraperitoneally with UDA at 20, 10, 5 or 0 mg/kg/day for 4 days. Treatment with UDA at 5 mg/kg significantly protected the mice against a lethal infection with mouse-adapted SARS-CoV (p<0.001), but did not significantly reduce virus lung titers. All virus-infected mice receiving UDA treatments were also significantly protected against weight loss (p<0.001). UDA also effectively reduced lung pathology scores. At day 6 after virus exposure, all groups of mice receiving UDA had much lower lung weights than did the placebo-treated mice. Thus, our data suggest that UDA treatment of SARS infection in mice leads to a substantial therapeutic effect that protects mice against death and weight loss. Furthermore, the mode of action of UDA in vitro was further investigated using live SARS-CoV Urbani strain virus and retroviral particles pseudotyped with SARS-CoV spike (S). UDA specifically inhibited the replication of live SARS-CoV or SARS-CoV pseudotyped virus when added just before, but not after, adsorption. These data suggested that UDA likely inhibits SARS-CoV infection by targeting early stages of the replication cycle, namely, adsorption or penetration. In addition, we demonstrated that UDA neutralizes the virus infectivity, presumably by binding to the SARS-CoV spike (S) glycoprotein. Finally, the target molecule for inhibition of virus

  20. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin.

    Science.gov (United States)

    Kumaki, Yohichi; Wandersee, Miles K; Smith, Aaron J; Zhou, Yanchen; Simmons, Graham; Nelson, Nathan M; Bailey, Kevin W; Vest, Zachary G; Li, Joseph K-K; Chan, Paul Kay-Sheung; Smee, Donald F; Barnard, Dale L

    2011-04-01

    Urtica dioica agglutinin (UDA) is a small plant monomeric lectin, 8.7 kDa in size, with an N-acetylglucosamine specificity that inhibits viruses from Nidovirales in vitro. In the current study, we first examined the efficacy of UDA on the replication of different SARS-CoV strains in Vero 76 cells. UDA inhibited virus replication in a dose-dependent manner and reduced virus yields of the Urbani strain by 90% at 1.1 ± 0.4 μg/ml in Vero 76 cells. Then, UDA was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. BALB/c mice were infected with two LD50 (575 PFU) of virus for 4 h before the mice were treated intraperitoneally with UDA at 20, 10, 5 or 0 mg/kg/day for 4 days. Treatment with UDA at 5 mg/kg significantly protected the mice against a lethal infection with mouse-adapted SARS-CoV (p < 0.001), but did not significantly reduce virus lung titers. All virus-infected mice receiving UDA treatments were also significantly protected against weight loss (p < 0.001). UDA also effectively reduced lung pathology scores. At day 6 after virus exposure, all groups of mice receiving UDA had much lower lung weights than did the placebo-treated mice. Thus, our data suggest that UDA treatment of SARS infection in mice leads to a substantial therapeutic effect that protects mice against death and weight loss. Furthermore, the mode of action of UDA in vitro was further investigated using live SARS-CoV Urbani strain virus and retroviral particles pseudotyped with SARS-CoV spike (S). UDA specifically inhibited the replication of live SARS-CoV or SARS-CoV pseudotyped virus when added just before, but not after, adsorption. These data suggested that UDA likely inhibits SARS-CoV infection by targeting early stages of the replication cycle, namely, adsorption or penetration. In addition, we demonstrated that UDA neutralizes the virus infectivity, presumably by binding to the SARS-CoV spike (S) glycoprotein. Finally, the target molecule for the inhibition of virus

  1. Cytoplasmic tail of coronavirus spike protein has intracellular

    Indian Academy of Sciences (India)

    https://www.ias.ac.in/article/fulltext/jbsc/042/02/0231-0244. Keywords. Coronavirus spike protein trafficking; cytoplasmic tail signal; endoplasmic reticulum–Golgi intermediate complex; lysosome. Abstract. Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spikeprotein is ...

  2. Imaging in severe acute respiratory syndrome (SARS)

    International Nuclear Information System (INIS)

    Antonio, G.E.; Wong, K.T.; Chu, W.C.W.; Hui, D.S.C.; Cheng, F.W.T.; Yuen, E.H.Y.; Chung, S.S.C.; Fok, T.F.; Sung, J.J.Y.; Ahuja, A.T.

    2003-01-01

    Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review

  3. HTCC: Broad Range Inhibitor of Coronavirus Entry.

    Directory of Open Access Journals (Sweden)

    Aleksandra Milewska

    Full Text Available To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1 circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl-3-trimethylammonium chitosan chloride (HTCC, and its hydrophobically-modified derivative (HM-HTCC as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.

  4. Bats and SARS

    Centers for Disease Control (CDC) Podcasts

    Bats are a natural reservoir for emerging viruses, among them henipaviruses and rabies virus variants. Dr. Nina Marano, Chief, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC, explains connection between horseshoe bats and SARS coronavirus transmission.

  5. Bats and SARS

    Centers for Disease Control (CDC) Podcasts

    2006-11-08

    Bats are a natural reservoir for emerging viruses, among them henipaviruses and rabies virus variants. Dr. Nina Marano, Chief, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC, explains connection between horseshoe bats and SARS coronavirus transmission.  Created: 11/8/2006 by Emerging Infectious Diseases.   Date Released: 11/17/2006.

  6. Characterization of a novel coronavirus associated with severe acute respiratory syndrome

    NARCIS (Netherlands)

    P.A. Rota (Paul); M.S. Oberste (Steven); S.S. Monroe (Stephan); W.A. Nix (Allan); R. Campagnoli (Ray); J.P. Icenogle (Joseph); S. Penaranda; B. Bankamp (Bettina); K. Maher (Kaija); M.H. Chen (Min-hsin); S. Tong (Suxiong); A. Tamin (Azaibi); L. Lowe (Luis); M. Frace (Michael); J.L. DeRisi (Joseph); Q. Chen (Qi); D. Wang (David); D.D. Erdman (Dean); T.C. Peret (Teresa); C. Burns (Cara); T.G. Ksiazek (Thomas); P.E. Rollin (Pierre); A. Sanchez (Berenguer); S. Liffick (Stephanie); B. Holloway (Brian); J. Limor (Josef); K. McCaustland (Karen); M. Olsen-Rasmussen (Mellissa); S. Gunther; A.D.M.E. Osterhaus (Albert); C. Drosten (Christian); M.A. Pallansch (Mark); L.J. Anderson (Larry); W.J. Belline; R.A.M. Fouchier (Ron)

    2003-01-01

    textabstractIn March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The

  7. Coronavirus Infection and Diversity in Bats in the Australasian Region.

    Science.gov (United States)

    Smith, C S; de Jong, C E; Meers, J; Henning, J; Wang, L- F; Field, H E

    2016-03-01

    Following the SARS outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. This study sought to identify the diversity and prevalence of coronaviruses in bats in the Australasian region. We identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. We did not detect any SARS-like betacoronaviruses, despite targeting rhinolophid bats, the putative natural host taxa. Our findings support the virus-host co-evolution hypothesis, with the detection of Miniopterus bat coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel betacoronavirus genotype from Pteropus alecto which is most closely related to Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the Philippines. We also detected possible cross-species transmission of bat coronaviruses, and the apparent enteric tropism of these viruses. Thus, our findings are consistent with a scenario wherein the current diversity and host specificity of coronaviruses reflects co-evolution with the occasional host shift.

  8. Evidence for an ancestral association of human coronavirus 229E with bats

    Czech Academy of Sciences Publication Activity Database

    Corman, V. M.; Baldwin, H. J.; Tateno, A. F.; Zerbinati, R. M.; Annan, A.; Owusu, M.; Nkrumah, E. E.; Maganga, G. D.; Oppong, S.; Adu-Sarkodie, Y.; Vallo, Peter; da Silva Filho, L. V. R. F.; Leroy, E. M.; Thiel, V.; van der Hoek, L.; Poon, L. L. M.; Tschapka, M.; Drosten, C.; Drexler, J. F.

    2015-01-01

    Roč. 89, č. 23 (2015), s. 11858-11870 ISSN 0022-538X Institutional support: RVO:68081766 Keywords : respiratory syndrome coronavirus * SARS-coronavirus * genomic characterization * dromedary camels * clinical impact * virus * children * protein * spike * classification Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 4.606, year: 2015

  9. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  10. Genetic Characteristics of Coronaviruses from Korean Bats in 2016.

    Science.gov (United States)

    Lee, Saemi; Jo, Seong-Deok; Son, Kidong; An, Injung; Jeong, Jipseol; Wang, Seung-Jun; Kim, Yongkwan; Jheong, Weonhwa; Oem, Jae-Ku

    2018-01-01

    Bats have increasingly been recognized as the natural reservoir of severe acute respiratory syndrome (SARS), coronavirus, and other coronaviruses found in mammals. However, little research has been conducted on bat coronaviruses in South Korea. In this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in South Korea. RT-PCR and sequencing were performed for specific coronavirus genes to identify the bat coronaviruses in different bat samples. Coronaviruses were detected in 2.7% (18/672) of the samples: 13 oral swabs from one species of the family Rhinolophidae, and four fecal samples and one carcass (intestine) from three species of the family Vespertiliodae. To determine the genetic relationships of the 18 sequences obtained in this study and previously known coronaviruses, the nucleotide sequences of a 392-nt region of the RNA-dependent RNA polymerase (RdRp) gene were analyzed phylogenetically. Thirteen sequences belonging to SARS-like betacoronaviruses showed the highest nucleotide identity (97.1-99.7%) with Bat-CoV-JTMC15 reported in China. The other five sequences were most similar to MERS-like betacoronaviruses. Four nucleotide sequences displayed the highest identity (94.1-95.1%) with Bat-CoV-HKU5 from Hong Kong. The one sequence from a carcass showed the highest nucleotide identity (99%) with Bat-CoV-SC2013 from China. These results suggest that careful surveillance of coronaviruses from bats should be continued, because animal and human infections may result from the genetic variants present in bat coronavirus reservoirs.

  11. SARS – Koch´Postulates proved.

    Indian Academy of Sciences (India)

    SARS – Koch´Postulates proved. Novel coronavirus identified from fluids of patients. Virus cultured in Vero cell line. Sera of patients have antibodies to virus. Cultured virus produces disease in Macaque monkeys. -produces specific immune response; -isolated virus is SARS CoV; -pathology similar to human.

  12. Simultaneous Genomic Detection of Multiple Enteric Bacterial and Viral Pathogens, Including Sars-CoV and RVFV

    National Research Council Canada - National Science Library

    Payne, S; Peters, C. J. (Clarence James), 1940; Makino, S; Oliver, K; Weiss, C; Kornguth, S; Carruthers, L; Chin, R

    2004-01-01

    ...) associated with the SARS-associated coronavirus (SARS-CoV) and Rift Valley Fever Virus (RVFV) has been developed. This system is based upon the Luminex xMAP" System, a multiplexed assay platform that combines high sample throughput...

  13. SARS – virus jumps species

    Indian Academy of Sciences (India)

    SARS – virus jumps species. Coronavirus reshuffles genes; Rotteir et al, Rotterdam showed the virus to jump from cats to mouse cells after single gene mutation ? Human disease due to virus jumping from wild or domestic animals; Present favourite animal - the cat; - edible or domestic.

  14. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

    has been shown by serologic and virological methods to infect coyotes. Dual infection with canine coronavirus and canine parvovirus causes fatal... attenuation and characteristics of a coronavirus-like agent. Am. J. Vet. Res. 34:145-150. Mebus, C.A., Stair, E.L., Rhodes, M.B., and Twiehaus, M.J. 1973b

  15. Genome organization of the SARS-CoV

    DEFF Research Database (Denmark)

    Xu, Jing; Hu, Jianfei; Wang, Jing

    2003-01-01

    Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or devel......Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available...

  16. Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Grum-Tokars, Valerie [Northwestern Univ., Chicago, IL (United States); Zhou, Ya [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Turlington, Mark [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Saldanha, S. Adrian [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Chase, Peter [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Eggler, Aimee [Purdue Univ., West Lafayette, IN (United States); Dawson, Eric S. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Baez-Santos, Yahira M. [Purdue Univ., West Lafayette, IN (United States); Tomar, Sakshi [Purdue Univ., West Lafayette, IN (United States); Mielech, Anna M. [Loyola Univ. Medical Center, Maywood, IL (United States); Baker, Susan C. [Loyola Univ. Medical Center, Maywood, IL (United States); Lindsley, Craig W. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Hodder, Peter [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Mesecar, Andrew [Purdue Univ., West Lafayette, IN (United States); Stauffer, Shaun R. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States)

    2012-12-11

    A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). But, unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure–activity relationships within S1', S1, and S2enzyme binding pockets. Moreover, the X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

  17. Mosaic Evolution of the Severe Acute Respiratory Syndrome Coronavirus

    Science.gov (United States)

    Stavrinides, John; Guttman, David S.

    2004-01-01

    Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans. PMID:14671089

  18. Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients

    DEFF Research Database (Denmark)

    Wu, Y P; Liu, Z H; Wei, R

    2009-01-01

    Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS-type pneum......Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS......-type pneumonia and the SARS-specific IgG response. Sixteen patients with SARS, 19 patients with community-acquired pneumonia (CAP) (Streptococcus pneumonia) and 16 healthy control subjects were enrolled in the study. Plasma SP-D and anti-SARS-CoV N protein IgG were measured using ELISA. SP-D was significantly...... elevated in SARS-type pneumonia [median (95% CI), 453 (379-963) ng/ml versus controls 218 (160-362) ng/ml, P protein IgG (r(2) = 0.5995, P = 0.02). The possible re-emergence of SARS or SARS-like infections suggests a need...

  19. Identification of Alpha and Beta Coronavirus in Wildlife Species in France: Bats, Rodents, Rabbits, and Hedgehogs

    Directory of Open Access Journals (Sweden)

    Elodie Monchatre-Leroy

    2017-11-01

    Full Text Available Coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV and Middle East Respiratory Syndrome-coronavirus (MERS-CoV, are known to cross the species barrier and eventually to move from wildlife to humans. Knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. This study explored the presence of coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs, and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The results obtained suggest the circulation of potentially evolving virus strains, with the potential to cross the species barrier.

  20. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kailang; Li, Weikai; Peng, Guiqing; Li, Fang; (Harvard-Med); (UMM-MED)

    2010-03-04

    NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.

  1. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture

    NARCIS (Netherlands)

    A.H. de Wilde (Adriaan); D. Jochmans (Dirk); C.C. Posthuma (Clara); J.C. Zevenhoven-Dobbe (Jessika); S. van Nieuwkoop (Stefan); T.M. Bestebroer (Theo); B.G. van den Hoogen (Bernadette); J. Neyts; E.J. Snijder (Eric)

    2014-01-01

    textabstractCoronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar

  2. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    International Nuclear Information System (INIS)

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-01-01

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

  3. Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus▿

    OpenAIRE

    Jung, Kwonil; Alekseev, Konstantin P.; Zhang, Xinsheng; Cheon, Doo-Sung; Vlasova, Anastasia N.; Saif, Linda J.

    2007-01-01

    The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] ...

  4. Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CL(pro)

    Energy Technology Data Exchange (ETDEWEB)

    Bacha,U.; Barilla, J.; Gabelli, S.; Kiso, Y.; Amzel, L.; Freire, E.

    2008-01-01

    Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CLpro (Mpro), which is highly conserved among all coronaviruses. Here 3CLpro derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CLpro with Ki's as low as 300 nm. The crystal structure of the complex of one of the compounds with 3CLpro indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.

  5. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences

    Czech Academy of Sciences Publication Activity Database

    Drexler, J. F.; Gloza-Rausch, F.; Glende, J.; Corman, V. M.; Muth, D.; Goettsche, M.; Seebens, A.; Niedrig, M.; Pfefferle, S.; Yordanov, S.; Zhelyazkov, L.; Hermanns, U.; Vallo, Peter; Lukashev, A.; Müller, M. A.; Deng, H.; Herrler, G.; Drosten, C.

    2010-01-01

    Roč. 84, č. 21 (2010), s. 11336-11349 ISSN 0022-538X Institutional research plan: CEZ:AV0Z60930519 Keywords : cross-species transmission * SARS-like coronavirus es * reservoir hosts * horseshoe bats Subject RIV: EE - Microbiology, Virology Impact factor: 5.189, year: 2010

  6. Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair

    DEFF Research Database (Denmark)

    Knudsen, T B; Kledal, T N; Andersen, O

    2003-01-01

    current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious...

  7. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition

    International Nuclear Information System (INIS)

    Versteeg, Gijs A.; Bredenbeek, Peter J.; Worm, Sjoerd H.E. van den; Spaan, Willy J.M.

    2007-01-01

    Many viruses encode antagonists to prevent interferon (IFN) induction. Infection of fibroblasts with the murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) did not result in nuclear translocation of interferon-regulatory factor 3 (IRF3), a key transcription factor involved in IFN induction, and induction of IFN mRNA transcription. Furthermore, MHV and SARS-CoV infection could not prevent IFN induction by poly (I:C) or Sendai virus, suggesting that these CoVs do not inactivate IRF3-mediated transcription regulation, but apparently prevent detection of replicative RNA by cellular sensory molecules. Our data indicate that shielding of viral RNA to host cell sensors might be the main general mechanism for coronaviruses to prevent IFN induction

  8. Understanding synergy.

    Science.gov (United States)

    Geary, Nori

    2013-02-01

    Analysis of the interactive effects of combinations of hormones or other manipulations with qualitatively similar individual effects is an important topic in basic and clinical endocrinology as well as other branches of basic and clinical research related to integrative physiology. Functional, as opposed to mechanistic, analyses of interactions rely on the concept of synergy, which can be defined qualitatively as a cooperative action or quantitatively as a supra-additive effect according to some metric for the addition of different dose-effect curves. Unfortunately, dose-effect curve addition is far from straightforward; rather, it requires the development of an axiomatic mathematical theory. I review the mathematical soundness, face validity, and utility of the most frequently used approaches to supra-additive synergy. These criteria highlight serious problems in the two most common synergy approaches, response additivity and Loewe additivity, which is the basis of the isobole and related response surface approaches. I conclude that there is no adequate, generally applicable, supra-additive synergy metric appropriate for endocrinology or any other field of basic and clinical integrative physiology. I recommend that these metrics be abandoned in favor of the simpler definition of synergy as a cooperative, i.e., nonantagonistic, effect. This simple definition avoids mathematical difficulties, is easily applicable, meets regulatory requirements for combination therapy development, and suffices to advance phenomenological basic research to mechanistic studies of interactions and clinical combination therapy research.

  9. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  10. SARS-CoV related Betacoronavirus and diverse Alphacoronavirus members found in western old-world.

    Science.gov (United States)

    Ar Gouilh, Meriadeg; Puechmaille, Sébastien J; Diancourt, Laure; Vandenbogaert, Mathias; Serra-Cobo, Jordi; Lopez Roïg, Marc; Brown, Paul; Moutou, François; Caro, Valérie; Vabret, Astrid; Manuguerra, Jean-Claude

    2018-04-01

    The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Differential sensitivity of bat cells to infection by enveloped RNA viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.

    Directory of Open Access Journals (Sweden)

    Markus Hoffmann

    Full Text Available Bats (Chiroptera host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat or Yangochiroptera (genera Carollia and Tadarida for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV, a porcine coronavirus, or to infection mediated by the Spike (S protein of SARS-coronavirus (SARS-CoV incorporated into pseudotypes based on vesicular stomatitis virus (VSV. The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3 were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.

  12. Detection of Coronaviruses in Bats of Various Species in Italy

    Directory of Open Access Journals (Sweden)

    Maria B. Boniotti

    2013-10-01

    Full Text Available Bats are natural reservoirs for many mammalian coronaviruses, which have received renewed interest after the discovery of the severe acute respiratory syndrome (SARS and the Middle East respiratory syndrome (MERS CoV in humans. This study describes the identification and molecular characterization of alphacoronaviruses and betacoronaviruses in bats in Italy, from 2010 to 2012. Sixty-nine faecal samples and 126 carcasses were tested using pan-coronavirus RT-PCR. Coronavirus RNAs were detected in seven faecal samples and nine carcasses. A phylogenetic analysis of RNA-dependent RNA polymerase sequence fragments aided in identifying two alphacoronaviruses from Kuhl’s pipistrelle (Pipistrellus kuhlii, three clade 2b betacoronaviruses from lesser horseshoe bats (Rhinolophus hipposideros, and 10 clade 2c betacoronaviruses from Kuhl’s pipistrelle, common noctule (Nyctalus noctula, and Savi’s pipistrelle (Hypsugo savii. This study fills a substantive gap in the knowledge on bat-CoV ecology in Italy, and extends the current knowledge on clade 2c betacoronaviruses with new sequences obtained from bats that have not been previously described as hosts of these viruses.

  13. Genetic diversity of coronaviruses in bats in Lao PDR and Cambodia.

    Science.gov (United States)

    Lacroix, Audrey; Duong, Veasna; Hul, Vibol; San, Sorn; Davun, Hull; Omaliss, Keo; Chea, Sokha; Hassanin, Alexandre; Theppangna, Watthana; Silithammavong, Soubanh; Khammavong, Kongsy; Singhalath, Sinpakone; Greatorex, Zoe; Fine, Amanda E; Goldstein, Tracey; Olson, Sarah; Joly, Damien O; Keatts, Lucy; Dussart, Philippe; Afelt, Aneta; Frutos, Roger; Buchy, Philippe

    2017-03-01

    South-East Asia is a hot spot for emerging zoonotic diseases, and bats have been recognized as hosts for a large number of zoonotic viruses such as Severe Acute Respiratory Syndrome (SARS), responsible for acute respiratory syndrome outbreaks. Thus, it is important to expand our knowledge of the presence of viruses in bats which could represent a risk to humans. Coronaviruses (CoVs) have been reported in bat species from Thailand, China, Indonesia, Taiwan and the Philippines. However no such work was conducted in Cambodia or Lao PDR. Between 2010 and 2013, 1965 bats were therefore sampled at interfaces with human populations in these two countries. They were tested for the presence of coronavirus by consensus reverse transcription-PCR assay. A total of 93 samples (4.7%) from 17 genera of bats tested positive. Sequence analysis revealed the presence of potentially 37 and 56 coronavirus belonging to alpha-coronavirus (αCoV) and beta-CoV (βCoV), respectively. The βCoVs group is known to include some coronaviruses highly pathogenic to human, such as SARS-CoV and MERS-CoV. All coronavirus sequences generated from frugivorous bats (family Pteropodidae) (n=55) clustered with other bat βCoVs of lineage D, whereas one coronavirus from Pipistrellus coromandra fell in the lineage C of βCoVs which also includes the MERS-CoV. αCoVs were all detected in various genera of insectivorous bats and clustered with diverse bat αCoV sequences previously published. A closely related strain of PEDV, responsible for severe diarrhea in pigs (PEDV-CoV), was detected in 2 Myotis bats. We highlighted the presence and the high diversity of coronaviruses circulating in bats from Cambodia and Lao PDR. Three new bat genera and species were newly identified as host of coronaviruses, namely Macroglossus sp., Megaerops niphanae and Myotis horsfieldii. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.

    Directory of Open Access Journals (Sweden)

    Eveline Kindler

    2017-02-01

    Full Text Available Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I. This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU activity is key to prevent early induction of double-stranded RNA (dsRNA host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

  15. Involvement of Autophagy in Coronavirus Replication

    Directory of Open Access Journals (Sweden)

    Paul Britton

    2012-11-01

    Full Text Available Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3 in coronavirus replication.

  16. High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.

    Science.gov (United States)

    Irigoyen, Nerea; Firth, Andrew E; Jones, Joshua D; Chung, Betty Y-W; Siddell, Stuart G; Brierley, Ian

    2016-02-01

    Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global "snap-shot" of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal

  17. High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.

    Directory of Open Access Journals (Sweden)

    Nerea Irigoyen

    2016-02-01

    Full Text Available Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV, are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global "snap-shot" of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59, a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the

  18. Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies

    Science.gov (United States)

    Geller, Chloé; Varbanov, Mihayl; Duval, Raphaël E.

    2012-01-01

    The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the

  19. Human coronavirus NL63, France

    NARCIS (Netherlands)

    Vabret, Astrid; Mourez, Thomas; Dina, Julia; van der Hoek, Lia; Gouarin, Stéphanie; Petitjean, Joëlle; Brouard, Jacques; Freymuth, François

    2005-01-01

    The human coronavirus NL63 (HCoV-NL63) was first identified in The Netherlands, and its circulation in France has not been investigated. We studied HCoV-NL63 infection in hospitalized children diagnosed with respiratory tract infections. From November 2002 to April 2003, we evaluated 300 respiratory

  20. SARS - Diagnosis

    Indian Academy of Sciences (India)

    SARS - Diagnosis. Mainly by exclusion of known causes of atypical pneumonia; * X ray Chest; * PCR on body fluids- primers defined by WHO centres available from website.-ve result does not exclude SARS. * Sequencing of amplicons; * Viral Cultures – demanding; * Antibody tests.

  1. Biodiversity impact of host interferon-stimulated-gene-product 15 on the coronavirus Papain-like protease deISGylase functions

    Science.gov (United States)

    Coronaviruses are single-stranded, positive sense RNA viruses whose members have severe impact on human health and cause significant economic hardships. Some pertinent examples include severe acute and Middle East respiratory syndromes (SARS-CoV; MERS-CoV), porcine epidemic diarrhea virus (PEDV), an...

  2. The emerging novel Middle East respiratory syndrome coronavirus: The “knowns” and “unknowns”

    Directory of Open Access Journals (Sweden)

    Jasper Fuk-Woo Chan

    2013-07-01

    Full Text Available A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012 (HCoV-EMC and recently renamed Middle East respiratory syndrome coronavirus (MERS-CoV, that is phylogenetically closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in 2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a severe acute respiratory syndrome (SARS-like infection in humans. The first laboratory-confirmed case, which involved a 60-year-old man from Bisha, the Kingdom of Saudi Arabia (KSA, who died of rapidly progressive community-acquired pneumonia and acute renal failure, was announced by the World Health Organization (WHO on September 23, 2012. Since then, a total of 70 cases, including 39 fatalities, have been reported in the Middle East and Europe. Recent clusters involving epidemiologically-linked household contacts and hospital contacts in the Middle East, Europe, and Africa strongly suggested possible human-to-human transmission. Clinical and laboratory research data generated in the past few months have provided new insights into the possible animal reservoirs, transmissibility, and virulence of MERS-CoV, and the optimal laboratory diagnostic options and potential antiviral targets for MERS-CoV-associated infection.

  3. Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.

    Science.gov (United States)

    Qu, Xiu-Xia; Hao, Pei; Song, Xi-Jun; Jiang, Si-Ming; Liu, Yan-Xia; Wang, Pei-Gang; Rao, Xi; Song, Huai-Dong; Wang, Sheng-Yue; Zuo, Yu; Zheng, Ai-Hua; Luo, Min; Wang, Hua-Lin; Deng, Fei; Wang, Han-Zhong; Hu, Zhi-Hong; Ding, Ming-Xiao; Zhao, Guo-Ping; Deng, Hong-Kui

    2005-08-19

    Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.

  4. Transmission of Middle East respiratory syndrome coronavirus ...

    African Journals Online (AJOL)

    ... hand hygiene, and cough etiquette, would minimize the infection rate among HCPs. The required consumables for maintaining hand hygiene should be readily available to all HCPs. Keywords: Middle East respiratory syndrome coronavirus (MERS-CoV), Systematic review, healthcareassociated infections, Coronaviruses ...

  5. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly, from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...

  6. Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fang (UMM)

    2008-09-23

    It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

  7. Molecular mechanisms of severe acute respiratory syndrome (SARS

    Directory of Open Access Journals (Sweden)

    Zabel Peter

    2005-01-01

    Full Text Available Abstract Severe acute respiratory syndrome (SARS is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

  8. BIOLOGICAL CLONING OF A BOVINE CORONAVIRUS ISOLATE

    OpenAIRE

    Betancourt, A; Rodríguez, Edisleidy; Relova, Damarys; Barrera, Maritza

    2008-01-01

    Con el objetivo de obtener un aislado de Coronavirus bovino clonado biológicamente se adaptó el aislado VB73/04 a la multiplicación en la línea celular MDBK. Este aislado indujo la formación de placas, las cuales resultaron homogéneas después del clonaje biológico. La población viral obtenida fue identificada como Coronavirus bovino por RT-PCR y Seroneutralización. In order to obtain a biologically cloned bovine coronavirus isolate, the isolate VB73/04 was adapted to multiplication in MDBK...

  9. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy

    Directory of Open Access Journals (Sweden)

    Kliger Yossef

    2003-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV, whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2 is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41 differs in length, and has no sequence homology with S2. Results Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1 an N-terminal leucine/isoleucine zipper-like sequence, and (2 a C-terminal heptad repeat located upstream of (3 an aromatic residue-rich region juxtaposed to the (4 transmembrane segment. Conclusions This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.

  10. A patient with asymptomatic severe acute respiratory syndrome (SARS) and antigenemia from the 2003-2004 community outbreak of SARS in Guangzhou, China.

    Science.gov (United States)

    Che, Xiao-yan; Di, Biao; Zhao, Guo-ping; Wang, Ya-di; Qiu, Li-wen; Hao, Wei; Wang, Ming; Qin, Peng-zhe; Liu, Yu-fei; Chan, Kwok-hong; Cheng, Vincent C C; Yuen, Kwok-yung

    2006-07-01

    An asymptomatic case of severe acute respiratory syndrome (SARS) occurred early in 2004, during a community outbreak of SARS in Guangzhou, China. This was the first time that a case of asymptomatic SARS was noted in an individual with antigenemia and seroconversion. The asymptomatic case patient and the second index case patient with SARS in the 2003-2004 outbreak both worked in the same restaurant, where they served palm civets, which were found to carry SARS-associated coronaviruses. Epidemiological information and laboratory findings suggested that the findings for the patient with asymptomatic infection, together with the findings from previously reported serological analyses of handlers of wild animals and the 4 index case patients from the 2004 community outbreak, reflected a likely intermediate phase of animal-to-human transmission of infection, rather than a case of human-to-human transmission. This intermediate phase may be a critical stage for virus evolution and disease prevention.

  11. Comparative properties of feline coronaviruses in vitro.

    OpenAIRE

    McKeirnan, A J; Evermann, J F; Davis, E V; Ott, R L

    1987-01-01

    Two feline coronaviruses were characterized to determine their biological properties in vitro and their antigenic relatedness to a previously recognized feline infectious peritonitis virus and canine coronavirus. The viruses, designated WSU 79-1146 and WSU 79-1683, were shown to have comparable growth curves with the prototype feline infectious peritonitis virus. Treatment of the feline infectious peritonitis virus strains with 0.25% trypsin indicated that they were relatively resistant to pr...

  12. Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

    Energy Technology Data Exchange (ETDEWEB)

    Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

    2010-01-01

    Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

  13. LHC-ILC synergy

    CERN Document Server

    Godbole, Rohini M

    2006-01-01

    I will begin by making a few general comments on the synergy between the Large Hadron Collider (LHC) which will go in action in 2007 and the International Linear Collider (ILC) which is under planning. I will then focus on the synergy between the LHC and the PLC option at the ILC, which is expected to be realised in the later stages of the ILC program. In this I will cover the possible synergy in the Higgs sector (with and without CP violation), in the determination of the anomalous vector boson couplings and last but not the least, in the search for extra dimensions and radions.

  14. Unraveling the Mysteries of Middle East Respiratory Syndrome Coronavirus

    Centers for Disease Control (CDC) Podcasts

    2014-03-11

    Dr. Aron Hall, a CDC coronavirus epidemiologist, discusses Middle East Respiratory Syndrome Coronavirus.  Created: 3/11/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/11/2014.

  15. Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus

    OpenAIRE

    Woo, Patrick C. Y.; Lau, Susanna K. P.; Lam, Carol S. F.; Lau, Candy C. Y.; Tsang, Alan K. L.; Lau, John H. N.; Bai, Ru; Teng, Jade L. L.; Tsang, Chris C. C.; Wang, Ming; Zheng, Bo-Jian; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2012-01-01

    Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sp...

  16. Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair

    DEFF Research Database (Denmark)

    Knudsen, T B; Kledal, T N; Andersen, O

    2003-01-01

    Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its...... disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common...... to the members of the coronavirus family, a model for host cell-virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain...

  17. Seeds and Synergies

    International Development Research Centre (IDRC) Digital Library (Canada)

    'Seeds and Synergies presents inspiring evidence of change in practice and policy ... Seeds of inspiration: breathing new life into the formal agricultural research .... and Urban Development and Poverty Alleviation and Agricultural Commodity ...

  18. Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS coronavirus

    Directory of Open Access Journals (Sweden)

    Júlia Vergara-Alert

    2017-06-01

    Full Text Available Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013–2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV, which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV, associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.

  19. Synergy in supramolecular chemistry

    CERN Document Server

    Nabeshima, Tatsuya

    2014-01-01

    Synergy and Cooperativity in Multi-metal Supramolecular Systems, T. NabeshimaHierarchically Assembled Titanium Helicates, Markus AlbrechtSupramolecular Hosts and Catalysts Formed by Self-assembly of Multinuclear Zinc Complexes in Aqueous Solution, Shin AokiSupramolecular Assemblies Based on Interionic Interactions, H. MaedaSupramolecular Synergy in the Formation and Function of Guanosine Quadruplexes, Jeffery T. DavisOn-Surface Chirality in Porous Self-Assembled Monolayers at Liquid-Solid Interface, Kazukuni Tahar

  20. A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

    Directory of Open Access Journals (Sweden)

    Berkhout Ben

    2005-02-01

    Full Text Available Abstract Background Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43 and 229E (HCoV-229E, SARS associated coronavirus (SARS-CoV and the recently identified human coronavirus NL63 (HCoV-NL63. In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. Methods Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. Results Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. Conclusions Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

  1. The role of viral population diversity in adaptation of bovine coronavirus to new host environments.

    Directory of Open Access Journals (Sweden)

    Monica K Borucki

    Full Text Available The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing and 38,000×(Illumina. The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were "selected" from a pre-existing pool rather than through de novo mutation and subsequent population fixation.

  2. Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease

    Science.gov (United States)

    Kim, Yunjeong; Mandadapu, Sivakoteswara Rao; Groutas, William C.; Chang, Kyeong-Ok

    2012-01-01

    Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC50 in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems. PMID:23219425

  3. Coronavirus infection, ER stress and Apoptosis

    Directory of Open Access Journals (Sweden)

    TO SING eFUNG

    2014-06-01

    Full Text Available The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER. Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR, a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus-host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP kinases activation, autophagy, apoptosis and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.

  4. Achieving a golden mean: mechanisms by which coronaviruses ensure synthesis of the correct stoichiometric ratios of viral proteins.

    Science.gov (United States)

    Plant, Ewan P; Rakauskaite, Rasa; Taylor, Deborah R; Dinman, Jonathan D

    2010-05-01

    In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.

  5. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.

    Directory of Open Access Journals (Sweden)

    Ji'an Pan

    Full Text Available Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12 provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

  6. Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang (UMMC)

    2012-12-10

    The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

  7. The lessons of SARS in Hong Kong.

    Science.gov (United States)

    Lai, Thomas Sik To; Yu, Wai Cho

    2010-02-01

    Severe acute respiratory syndrome (SARS) is a novel coronavirus infection which broke out in Hong Kong in March 2003. Princess Margaret Hospital was designated to manage this new, mysterious and serious disease. Healthcare workers had to work under extremely stressful and often risky conditions to care for patients. Despite manpower and equipment reinforcements, staff infection occurred as a result of bodily exhaustion, working in an unfamiliar environment and lapses in infection control. Patients suffered even more, not only due to physical discomfort, but also because of the fear of isolation and death away from family and friends. Health authorities learnt their lessons in the outbreak and formulated emergency plans for future infectious disease epidemics. The healthcare infrastructure has been examined and upgraded with regard to intensive care capacity, infection control measures, professional training, manpower deployment, staff facilities, and stockpiling of drugs and personal protective equipment.

  8. Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein

    OpenAIRE

    Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R.

    2012-01-01

    This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for non-invasive receptor mediated gene delivery to na...

  9. MERS-coronavirus: From discovery to intervention

    NARCIS (Netherlands)

    W. Widagdo; N.M.A. Okba (Nisreen); V. Stalin Raj; B.L. Haagmans (Bart)

    2017-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. Here we describe the current epidemiological picture of MERS-CoV, focusing on humans

  10. Coronavirus infection of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Horzinek, M C; Rottier, P J

    1995-01-01

    Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

  11. Dynamics of the coronavirus replicative structures

    NARCIS (Netherlands)

    Hagemeijer, M.C.

    2011-01-01

    Coronaviruses (CoV) are positive-strand RNA (+RNA) viruses that are important infectious agents in both animals and man. Upon infection, CoVs generate large multicomponent protein complexes, consisting of 16 nonstructural proteins (nsp’s) and yet to be identified cellular proteins, dedicated to the

  12. Canine coronaviruses: Epidemiology, evolution and pathobiology

    NARCIS (Netherlands)

    Decaro, N.

    2009-01-01

    Coronaviruses (CoVs; order Nidovirales, family Coronaviridae) are viruses exceptionally prone to genetic evolution through the continual accumulation of mutations and by homologous recombination between related members. CoVs are organised into three antigenic groups of which group 1 is subdivided in

  13. Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9

    OpenAIRE

    Wei, Pengfei; Cai, Zelang; Hua, Jinwen; Yu, Weijia; Chen, Jiajie; Kang, Kang; Qiu, Congling; Ye, Lanlan; Hu, Jiayun; Ji, Kunmei

    2016-01-01

    Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China’s infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) e...

  14. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Nielsen, M; Lamberth, K

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...... of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design....

  15. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly, from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...... of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design....

  16. Coronavirus infections in horses in Saudi Arabia and Oman.

    Science.gov (United States)

    Hemida, M G; Chu, D K W; Perera, R A P M; Ko, R L W; So, R T Y; Ng, B C Y; Chan, S M S; Chu, S; Alnaeem, A A; Alhammadi, M A; Webby, R J; Poon, L L M; Balasuriya, U B R; Peiris, M

    2017-12-01

    Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT-PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT-PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross-reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections. © 2017 Blackwell Verlag GmbH.

  17. Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double recombination between feline coronavirus type I and canine coronavirus

    NARCIS (Netherlands)

    Horzinek, M.C.; Herrewegh, A.A.; Rottier, P.J.M.; Groot, R.J. de

    1998-01-01

    Recent evidence suggests that the type II feline coronavirus (FCoV) strains 79-1146 and 79-1683 have arisen from a homologous RNA recombination event between FCoV type I and canine coronavirus (CCV). In both cases, the template switch apparently took place between the S and M genes, giving rise to

  18. Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses.

    Science.gov (United States)

    Agnihothram, Sudhakar; Gopal, Robin; Yount, Boyd L; Donaldson, Eric F; Menachery, Vineet D; Graham, Rachel L; Scobey, Trevor D; Gralinski, Lisa E; Denison, Mark R; Zambon, Maria; Baric, Ralph S

    2014-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.  Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.  Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.  Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.

  19. Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

    Science.gov (United States)

    Jiang, Shibo; Bottazzi, Maria Elena; Du, Lanying; Lustigman, Sara; Tseng, Chien-Te Kent; Curti, Elena; Jones, Kathryn; Zhan, Bin; Hotez, Peter J

    2013-01-01

    A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years. PMID:23252385

  20. Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

    Energy Technology Data Exchange (ETDEWEB)

    Pak, J.; Sharon, C; Satkunarajah, M; Thierry, C; Cameron, C; Kelvin, D; Seetharaman, J; Cochrane, A; Plummer, F; et. al.

    2009-01-01

    The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.

  1. Infection control for SARS in a tertiary neonatal centre.

    Science.gov (United States)

    Ng, P C; So, K W; Leung, T F; Cheng, F W T; Lyon, D J; Wong, W; Cheung, K L; Fung, K S C; Lee, C H; Li, A M; Hon, K L E; Li, C K; Fok, T F

    2003-09-01

    The Severe Acute Respiratory Syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus, which can readily spread in the healthcare setting. A recent community outbreak in Hong Kong infected a significant number of pregnant women who subsequently required emergency caesarean section for deteriorating maternal condition and respiratory failure. As no neonatal clinician has any experience in looking after these high risk infants, stringent infection control measures for prevention of cross infection between patients and staff are important to safeguard the wellbeing of the work force and to avoid nosocomial spread of SARS within the neonatal unit. This article describes the infection control and patient triage policy of the neonatal unit at the Prince of Wales Hospital, Hong Kong. We hope this information is useful in helping other units to formulate their own infection control plans according to their own unit configuration and clinical needs.

  2. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses.

    Science.gov (United States)

    Wu, Kailang; Chen, Lang; Peng, Guiqing; Zhou, Wenbo; Pennell, Christopher A; Mansky, Louis M; Geraghty, Robert J; Li, Fang

    2011-06-01

    How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.

  3. Synergies between energy supply networks

    DEFF Research Database (Denmark)

    Wu, Jianzhnog; Yan, Jinyue; Desideri, Umberto

    2017-01-01

    Energy system integration uses a whole-system approach to optimize the synergies between energy supply networks to facilitate and coordinate the grid integration of distributed energy resources while enabling the synergies and conflicts between the local distribution networks and the national lev...... and integration of local renewables including solar energy wind geothermal waste heat and biomass is presented.......Energy system integration uses a whole-system approach to optimize the synergies between energy supply networks to facilitate and coordinate the grid integration of distributed energy resources while enabling the synergies and conflicts between the local distribution networks and the national level...... objectives to be understood and optimally coordinated. The latest research on the network coupling technologies analysis of synergies between energy supply networks and optimal use of synergies in network operation is discussed. A diagram on the possible interactions between different energy networks...

  4. Keynote presentation : SAR systems

    NARCIS (Netherlands)

    Halsema, D. van; Otten, M.P.G.; Maas, A.P.M.; Bolt, R.J.; Anitori, L.

    2011-01-01

    Synthetic Aperture Radar (SAR) systems are becoming increasingly important sensors in as well the military environment as in the civilian market. In this keynote presentation an overview will be given over more than 2 decades of SAR system∼ and SAR application development at TNO in the Netherlands.

  5. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  6. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  7. Hand Grasping Synergies As Biometrics.

    Science.gov (United States)

    Patel, Vrajeshri; Thukral, Poojita; Burns, Martin K; Florescu, Ionut; Chandramouli, Rajarathnam; Vinjamuri, Ramana

    2017-01-01

    Recently, the need for more secure identity verification systems has driven researchers to explore other sources of biometrics. This includes iris patterns, palm print, hand geometry, facial recognition, and movement patterns (hand motion, gait, and eye movements). Identity verification systems may benefit from the complexity of human movement that integrates multiple levels of control (neural, muscular, and kinematic). Using principal component analysis, we extracted spatiotemporal hand synergies (movement synergies) from an object grasping dataset to explore their use as a potential biometric. These movement synergies are in the form of joint angular velocity profiles of 10 joints. We explored the effect of joint type, digit, number of objects, and grasp type. In its best configuration, movement synergies achieved an equal error rate of 8.19%. While movement synergies can be integrated into an identity verification system with motion capture ability, we also explored a camera-ready version of hand synergies-postural synergies. In this proof of concept system, postural synergies performed well, but only when specific postures were chosen. Based on these results, hand synergies show promise as a potential biometric that can be combined with other hand-based biometrics for improved security.

  8. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection.

    Directory of Open Access Journals (Sweden)

    Tomoki Yoshikawa

    2010-01-01

    Full Text Available Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV. Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NFkappaB, activator protein (AP-1, and interferon regulatory factor (IRF-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i., resulting in the activation of many antiviral genes, including interferon (IFN-beta, -lambdas, inflammatory mediators, and many IFN-stimulated genes (ISGs. We also showed, for the first time, that IFN-beta and IFN-lambdas were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.

  9. From silos to synergy.

    Science.gov (United States)

    Treadwell, Janet; Levermann, Laurie; Soffar, Gail; Giardino, Angelo

    2007-08-01

    Texas Children's Health Plan (TCHP) redesigned its approach to care management in an effort to provide support for member-centric care and the medical home. The changes in process and structure focused on connecting information and programs to promote care for members in a collaborative manner and taking advantage of the synergy between staff, programming, and the physician practices serving health plan membership. The results brought about an improvement in job satisfaction, positive change in the medical-loss ratio, and new innovations to support preventive and chronic care service delivery needs of the TCHP membership.

  10. Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug Design

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Xiaoyu; Yu, Hongwei; Yang, Haitao; Xue, Fei; Wu, Zhixin; Shen, Wei; Li, Jun; Zhou, Zhe; Ding, Yi; Zhao, Qi; Zhang, Xuejun C.; Liao, Ming; Bartlam, Mark; Rao, Zihe (SCAU); (Tsinghua); (Chinese Aca. Sci.)

    2008-07-21

    Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M{sup pro}), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) MP{sup pro} and a severe acute respiratory syndrome CoV (SARS-CoV) M{sup pro} mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M{sup pro}. A monomeric form of IBV M{sup pro} was identified for the first time in CoV M{sup pro} structures. A comparison of these two structures to other available M{sup pro} structures provides new insights for the design of substrate-based inhibitors targeting CoV M{sup pro}s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M{sup pro} and was found to demonstrate in vitro inactivation of IBV M{sup pro} and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M{sup pro}.

  11. Altered pathogenesis of porcine respiratory coronavirus in pigs due to immunosuppressive effects of dexamethasone: implications for corticosteroid use in treatment of severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Jung, Kwonil; Alekseev, Konstantin P; Zhang, Xinsheng; Cheon, Doo-Sung; Vlasova, Anastasia N; Saif, Linda J

    2007-12-01

    The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-gamma)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-gamma-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans

  12. Yeast based small molecule screen for inhibitors of SARS-CoV.

    Directory of Open Access Journals (Sweden)

    Matthew Frieman

    Full Text Available Severe acute respiratory coronavirus (SARS-CoV emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.

  13. A Typical Synergy

    Science.gov (United States)

    van Noort, Thomas; Achten, Peter; Plasmeijer, Rinus

    We present a typical synergy between dynamic types (dynamics) and generalised algebraic datatypes (GADTs). The former provides a clean approach to integrating dynamic typing in a statically typed language. It allows values to be wrapped together with their type in a uniform package, deferring type unification until run time using a pattern match annotated with the desired type. The latter allows for the explicit specification of constructor types, as to enforce their structural validity. In contrast to ADTs, GADTs are heterogeneous structures since each constructor type is implicitly universally quantified. Unfortunately, pattern matching only enforces structural validity and does not provide instantiation information on polymorphic types. Consequently, functions that manipulate such values, such as a type-safe update function, are cumbersome due to boilerplate type representation administration. In this paper we focus on improving such functions by providing a new GADT annotation via a natural synergy with dynamics. We formally define the semantics of the annotation and touch on novel other applications of this technique such as type dispatching and enforcing type equality invariants on GADT values.

  14. [SARS: a new emergency in the world health].

    Science.gov (United States)

    Calza, Leonardo; Manfredi, Roberto; Verucchi, Gabriella; Chiodo, Francesco

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is a new life-threatening respiratory disease which has its origins in Guangdong province, China, where the earliest known cases were identified in November 2002. Since then, probable cases of SARS have been reported in 30 countries and the current cumulative number of cases is 8,240 with 745 deaths and a global fatality rate of 9%. The most frequently involved areas include China, Hong Kong, Singapore, Canada, Vietnam and Philippines. Most cases of SARS to date have occurred in young adults and this disease appears to spread most commonly by close person-to-person contact, involving exposure to infectious droplets and body fluids. This transmission pattern generally involves household members, health care workers and international travellers, while a large and sudden cluster of almost simultaneous cases in an housing estate of Hong Kong has raised the possibility of transmission from an environmental source. The most common presenting symptoms are fever, malaise, non-productive cough and dyspnea, associated with pulmonary interstitial infiltrates on chest radiography. A novel coronavirus is associated with this outbreak, and the laboratory evidences indicate that this virus has an etiologic role in SARS, but the role of other concurrent viral agents (such as metapneumovirus) identified in these patients requires further investigation.

  15. Hand Grasping Synergies As Biometrics

    Directory of Open Access Journals (Sweden)

    Ramana Vinjamuri

    2017-05-01

    Full Text Available Recently, the need for more secure identity verification systems has driven researchers to explore other sources of biometrics. This includes iris patterns, palm print, hand geometry, facial recognition, and movement patterns (hand motion, gait, and eye movements. Identity verification systems may benefit from the complexity of human movement that integrates multiple levels of control (neural, muscular, and kinematic. Using principal component analysis, we extracted spatiotemporal hand synergies (movement synergies from an object grasping dataset to explore their use as a potential biometric. These movement synergies are in the form of joint angular velocity profiles of 10 joints. We explored the effect of joint type, digit, number of objects, and grasp type. In its best configuration, movement synergies achieved an equal error rate of 8.19%. While movement synergies can be integrated into an identity verification system with motion capture ability, we also explored a camera-ready version of hand synergies—postural synergies. In this proof of concept system, postural synergies performed well, but only when specific postures were chosen. Based on these results, hand synergies show promise as a potential biometric that can be combined with other hand-based biometrics for improved security.

  16. Evidence supporting a zoonotic origin of human coronavirus strain NL63.

    Science.gov (United States)

    Huynh, Jeremy; Li, Shimena; Yount, Boyd; Smith, Alexander; Sturges, Leslie; Olsen, John C; Nagel, Juliet; Johnson, Joshua B; Agnihothram, Sudhakar; Gates, J Edward; Frieman, Matthew B; Baric, Ralph S; Donaldson, Eric F

    2012-12-01

    The relationship between bats and coronaviruses (CoVs) has received considerable attention since the severe acute respiratory syndrome (SARS)-like CoV was identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then, several bats throughout the world have been shown to shed CoV sequences, and presumably CoVs, in the feces; however, no bat CoVs have been isolated from nature. Moreover, there are very few bat cell lines or reagents available for investigating CoV replication in bat cells or for isolating bat CoVs adapted to specific bat species. Here, we show by molecular clock analysis that alphacoronavirus (α-CoV) sequences derived from the North American tricolored bat (Perimyotis subflavus) are predicted to share common ancestry with human CoV (HCoV)-NL63, with the most recent common ancestor between these viruses occurring approximately 563 to 822 years ago. Further, we developed immortalized bat cell lines from the lungs of this bat species to determine if these cells were capable of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains replicated inefficiently, HCoV-NL63 replicated for multiple passages in the immortalized lung cells from this bat species. These observations support the hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic transmission cycles that may allow some CoVs to readily circulate and exchange genetic material between strains found in bats and other mammals, including humans.

  17. Geneva international synergies

    CERN Multimedia

    2010-01-01

    Geneva has a long history of hosting international organizations, which is part of the reason why CERN is here, and it makes the canton an ideal place to forge links between such organizations. Over recent weeks, CERN has signed agreements with the ITU, WIPO and the WMO. At first sight, there may not seem to be much common ground between CERN and, say, the World Meteorological Organization, but scratch the surface, and you’ll soon find a common thread. All of these organizations have a vocation to stimulate technological innovation, and together we’re stronger.   Let’s start with ITU, the International Telecommunications Union. There, the synergies are evident. When ITU organized the World Summit on the Information Society in 2003, CERN provided a significant side event examining the Role of Science in the Information Society. The current agreement builds on that, allowing our two organizations to work together on important societal issues such as the extension of b...

  18. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.

    Science.gov (United States)

    Woo, Patrick C Y; Lau, Susanna K P; Lam, Carol S F; Lau, Candy C Y; Tsang, Alan K L; Lau, John H N; Bai, Ru; Teng, Jade L L; Tsang, Chris C C; Wang, Ming; Zheng, Bo-Jian; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2012-04-01

    Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.

  19. An empirical InSAR-optical fusion approach to mapping vegetation canopy height

    Science.gov (United States)

    Wayne S. Walker; Josef M. Kellndorfer; Elizabeth LaPoint; Michael Hoppus; James Westfall

    2007-01-01

    Exploiting synergies afforded by a host of recently available national-scale data sets derived from interferometric synthetic aperture radar (InSAR) and passive optical remote sensing, this paper describes the development of a novel empirical approach for the provision of regional- to continental-scale estimates of vegetation canopy height. Supported by data from the...

  20. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

    Full Text Available Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP, can arise through mutation of FECV to FIP virus (FIPV. The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for

  1. Diagnostic Methods for Feline Coronavirus: A Review

    Directory of Open Access Journals (Sweden)

    Saeed Sharif

    2010-01-01

    Full Text Available Feline coronaviruses (FCoVs are found throughout the world. Infection with FCoV can result in a diverse range of signs from clinically inapparent infections to a highly fatal disease called feline infectious peritonitis (FIP. FIP is one of the most serious viral diseases of cats. While there is neither an effective vaccine, nor a curative treatment for FIP, a diagnostic protocol for FCoV would greatly assist in the management and control of the virus. Clinical findings in FIP are non-specific and not helpful in making a differential diagnosis. Haematological and biochemical abnormalities in FIP cases are also non-specific. The currently available serological tests have low specificity and sensitivity for detection of active infection and cross-react with FCoV strains of low pathogenicity, the feline enteric coronaviruses (FECV. Reverse transcriptase polymerase chain reaction (RT-PCR has been used to detect FCoV and is rapid and sensitive, but results must be interpreted in the context of clinical findings. At present, a definitive diagnosis of FIP can be established only by histopathological examination of biopsies. This paper describes and compares diagnostic methods for FCoVs and includes a brief account of the virus biology, epidemiology, and pathogenesis.

  2. SYNERGY EFFECTS IN WORK TEAMS

    OpenAIRE

    Raluca C. Zoltan

    2014-01-01

    Today’s organization increasingly utilizes all kind of teams in order to surpass their competitors through flexibility, adaptability and innovation, features which are seen to characterize the teams. For this purpose, the concept of synergy in teams’ activity is often mentioned as the prime reason for which collective work is considered to be superior comparative with individual work. But what exactly does it mean? The present paper aims to shed some light on the concept of synergy in work te...

  3. Antibody response to equine coronavirus in horses inoculated with a bovine coronavirus vaccine.

    Science.gov (United States)

    Nemoto, Manabu; Kanno, Toru; Bannai, Hiroshi; Tsujimura, Koji; Yamanaka, Takashi; Kokado, Hiroshi

    2017-11-17

    A vaccine for equine coronavirus (ECoV) is so far unavailable. Bovine coronavirus (BCoV) is antigenically related to ECoV; it is therefore possible that BCoV vaccine will induce antibodies against ECoV in horses. This study investigated antibody response to ECoV in horses inoculated with BCoV vaccine. Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. This study showed that BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether antibodies provided by BCoV vaccine are effective against ECoV, and therefore ECoV challenge studies are needed to evaluate efficacy of the vaccine in the future.

  4. Coronavirus 229E-related pneumonia in immunocompromised patients.

    Science.gov (United States)

    Pene, Frédéric; Merlat, Annabelle; Vabret, Astrid; Rozenberg, Flore; Buzyn, Agnès; Dreyfus, François; Cariou, Alain; Freymuth, François; Lebon, Pierre

    2003-10-01

    Coronaviruses strains 229E and OC43 have been associated with various respiratory illnesses ranging from the self-resolving common cold to severe pneumonia. Although chronic underlying conditions are major determinants of severe respiratory virus infections, few data about coronavirus-related pneumonia in immunocompromised patients are available. Here we report 2 well-documented cases of pneumonia related to coronavirus 229E, each with a different clinical presentation. Diagnosis was made on the basis of viral culture and electron microscopy findings that exhibited typical crown-like particles and through amplification of the viral genome by reverse transcriptase-polymerase chain reaction. On the basis of this report, coronaviruses should be considered as potential causative microorganisms of pneumonia in immunocompromised patients.

  5. Molecular and pathological identification of feline coronavirus type I

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-06-05

    Jun 5, 2012 ... In this study, we described the isolation and molecular characterization of .... fecv2b) designed in the regions of S-protein gene were used to differentiate ..... The molecular dynamics of feline coronaviruses. Vet. Microbiol.

  6. Spike Protein Fusion Peptide and Feline Coronavirus Virulence

    Science.gov (United States)

    Chang, Hui-Wen; Egberink, Herman F.; Halpin, Rebecca; Spiro, David J.

    2012-01-01

    Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically. PMID:22709821

  7. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara

    2015-10-15

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR\\'s ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  8. Forest Biomass Mapping From Lidar and Radar Synergies

    Science.gov (United States)

    Sun, Guoqing; Ranson, K. Jon; Guo, Z.; Zhang, Z.; Montesano, P.; Kimes, D.

    2011-01-01

    The use of lidar and radar instruments to measure forest structure attributes such as height and biomass at global scales is being considered for a future Earth Observation satellite mission, DESDynI (Deformation, Ecosystem Structure, and Dynamics of Ice). Large footprint lidar makes a direct measurement of the heights of scatterers in the illuminated footprint and can yield accurate information about the vertical profile of the canopy within lidar footprint samples. Synthetic Aperture Radar (SAR) is known to sense the canopy volume, especially at longer wavelengths and provides image data. Methods for biomass mapping by a combination of lidar sampling and radar mapping need to be developed. In this study, several issues in this respect were investigated using aircraft borne lidar and SAR data in Howland, Maine, USA. The stepwise regression selected the height indices rh50 and rh75 of the Laser Vegetation Imaging Sensor (LVIS) data for predicting field measured biomass with a R(exp 2) of 0.71 and RMSE of 31.33 Mg/ha. The above-ground biomass map generated from this regression model was considered to represent the true biomass of the area and used as a reference map since no better biomass map exists for the area. Random samples were taken from the biomass map and the correlation between the sampled biomass and co-located SAR signature was studied. The best models were used to extend the biomass from lidar samples into all forested areas in the study area, which mimics a procedure that could be used for the future DESDYnI Mission. It was found that depending on the data types used (quad-pol or dual-pol) the SAR data can predict the lidar biomass samples with R2 of 0.63-0.71, RMSE of 32.0-28.2 Mg/ha up to biomass levels of 200-250 Mg/ha. The mean biomass of the study area calculated from the biomass maps generated by lidar- SAR synergy 63 was within 10% of the reference biomass map derived from LVIS data. The results from this study are preliminary, but do show the

  9. [Epidemiological perspectives on SARS and avian influenza].

    Science.gov (United States)

    del Rey Calero, Juan

    2004-01-01

    SARS is a respiratory infection caused by Coronavirus (Nidoviruses, RNA) from which 3 groups are known. Group 1 affects dogs, cats, pigs, and the human agent is 229 E. Group 2 affects bovines or rodents, and the human agent is OC43. And group 3 corresponds to the avian pathology.... The epidemics emerged on February 2003 in Guangdong, South China, due to consumption of exotic animals (Civeta, etc.), and it spread through interperson contagion to other regions in Asia, America and Europe. Incubation period is about 2-7 days. Transmission Of the virus is person-to person, but also by excretions and residual water. Basic reproductive rate is 2 to 4, and it is considered that 2.7 persons are infected from the initial case. In June 2003, SARS affected over 8,000 people and 774 were killed. Mortality approaches to 10%, and it is higher among older people rising up to 50% in those aged over 65 years. It is important to quickly establish action protocols regarding clinical, epidemiological and prevention aspects. Avian influenza is an infection caused by type A Influenza Orthomixovirus, in which migration birds and wild ducks are the main reservoir. Avian viruses correspond to H5, H7, H9. In 1997 it was observed that type AH5N1 jumped interspecies barrier and affected 18 humans, and 6 of them died. At the end of 2003 and in 2004 this type of poultry flu was described in Asia. FAO has emphasized that sacrifice of chicken in affected farms is the most effective measure to fight against the disease. It has also been established suppression of imports from these countries. There is no evidence on interperson contagion from chicken contagion, nor on food-borne contagion to humans.

  10. European Surveillance for Pantropic Canine Coronavirus

    Science.gov (United States)

    Cordonnier, Nathalie; Demeter, Zoltan; Egberink, Herman; Elia, Gabriella; Grellet, Aurélien; Le Poder, Sophie; Mari, Viviana; Martella, Vito; Ntafis, Vasileios; von Reitzenstein, Marcela; Rottier, Peter J.; Rusvai, Miklos; Shields, Shelly; Xylouri, Eftychia; Xu, Zach; Buonavoglia, Canio

    2013-01-01

    Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5′ end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains. PMID:23100349

  11. The persistent prevalence and evolution of cross-family recombinant coronavirus GCCDC1 among a bat population: a two-year follow-up.

    Science.gov (United States)

    Obameso, Joseph O; Li, Hong; Jia, Hao; Han, Min; Zhu, Shiyan; Huang, Canping; Zhao, Yuhui; Zhao, Min; Bai, Yu; Yuan, Fei; Zhao, Honglan; Peng, Xia; Xu, Wen; Tan, Wenjie; Zhao, Yingze; Yuen, Kwok-Yung; Liu, William J; Lu, Lin; Gao, George F

    2017-12-01

    Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.

  12. Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis.

    Science.gov (United States)

    Tekes, G; Thiel, H-J

    2016-01-01

    Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV). The review summarizes our current knowledge of the genome and proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike) protein S and the five accessory proteins. We also review the current classification of FCoVs into distinct serotypes and biotypes, cellular receptors of FCoVs and their presumed role in viral virulence, and discuss other aspects of FIPV-induced pathogenesis. Our current knowledge of genetic differences between FECVs and FIPVs has been mainly based on comparative sequence analyses that revealed "discriminatory" mutations that are present in FIPVs but not in FECVs. Most of these mutations result in amino acid substitutions in the S protein and these may have a critical role in the switch from FECV to FIPV. In most cases, the precise roles of these mutations in the molecular pathogenesis of FIP have not been tested experimentally in the natural host, mainly due to the lack of suitable experimental tools including genetically engineered virus mutants. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies. © 2016 Elsevier Inc. All rights reserved.

  13. Mesodynamics in the SARS nucleocapsid measured by NMR field cycling

    Energy Technology Data Exchange (ETDEWEB)

    Clarkson, Michael W.; Lei Ming; Eisenmesser, Elan Z.; Labeikovsky, Wladimir [MS009 Brandeis University, Department of Biochemistry and Howard Hughes Medical Institute (United States); Redfield, Alfred [MS009 Brandeis University, Department of Biochemistry (United States)], E-mail: redfield@brandeis.edu; Kern, Dorothee [MS009 Brandeis University, Department of Biochemistry and Howard Hughes Medical Institute (United States)], E-mail: dkern@brandeis.edu

    2009-09-15

    Protein motions on all timescales faster than molecular tumbling are encoded in the spectral density. The dissection of complex protein dynamics is typically performed using relaxation rates determined at high and ultra-high field. Here we expand this range of the spectral density to low fields through field cycling using the nucleocapsid protein of the SARS coronavirus as a model system. The field-cycling approach enables site-specific measurements of R{sub 1} at low fields with the sensitivity and resolution of a high-field magnet. These data, together with high-field relaxation and heteronuclear NOE, provide evidence for correlated rigid-body motions of the entire {beta}-hairpin, and corresponding motions of adjacent loops with a time constant of 0.8 ns (mesodynamics). MD simulations substantiate these findings and provide direct verification of the time scale and collective nature of these motions.

  14. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara; Rockwood, Alyn; Ghanem, Bernard

    2015-01-01

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR's ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  15. Emergence of pathogenic coronaviruses in cats by homologous recombination between feline and canine coronaviruses.

    Directory of Open Access Journals (Sweden)

    Yutaka Terada

    Full Text Available Type II feline coronavirus (FCoV emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV. In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3'-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5'-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.

  16. Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus

    Directory of Open Access Journals (Sweden)

    Mark W. Jackwood

    2011-09-01

    Full Text Available Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.

  17. Synergy disclosures in mergers and acquisitions

    NARCIS (Netherlands)

    M.D.R.P. Dutordoir (Marie); P.G.J. Roosenboom (Peter); M. Teixeira de Vasconcelos (Manuel)

    2013-01-01

    textabstractWe examine bidding firms’ motives for disclosing a synergy forecast when announcing a merger or acquisition. Our sample consists of 1,990 M&A deals, of which 345 announce synergy estimates. Our results suggest that synergy disclosures serve to obtain a more favorable market reception for

  18. Entrepreneurial Creativity through Motivational Synergy.

    Science.gov (United States)

    Amabile, Teresa M.

    1997-01-01

    Defines and describes entrepreneurial creativity, which is the generation and implementation of novel, appropriate ideas to establish a new venture. Discusses the need for motivational synergy, which results when strong levels of personal interest and involvement are combined with the promise of rewards that confirm competence. (Author/CR)

  19. Coronaviruses in brain tissue from patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Dessau, R B; Lisby, G; Frederiksen, J L

    2001-01-01

    Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E...... and three PCR assays with primers specific for the nucleocapsid protein of human coronavirus strain OC43 were performed. Sporadic positive PCR assays were observed in both patients and controls in some of the PCR assays. However, these results were not reproducible and there was no difference...... in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study....

  20. Genotyping coronaviruses associated with feline infectious peritonitis.

    Science.gov (United States)

    Lewis, Catherine S; Porter, Emily; Matthews, David; Kipar, Anja; Tasker, Séverine; Helps, Christopher R; Siddell, Stuart G

    2015-06-01

    Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP. © 2015 The Authors.

  1. Coronavirus 3CL(pro) proteinase cleavage sites: Possible relevance to SARS virus pathology

    DEFF Research Database (Denmark)

    Kiemer, Lars; Lund, Ole; Brunak, Søren

    2004-01-01

    the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection...

  2. The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Zhong, Fei; Chow, Vincent T K

    2007-01-01

    Da glycosylated protein. It was not secreted in the presence of tunicamycin and was detected as a 130 kDa protein in the cell lysate. The purified S-protein bound to Vero but not 293T cells and was itself recognized by lung surfactant protein D (SP-D), a collectin found in the lung alveoli. The binding required...

  3. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  4. Crop Classification by Polarimetric SAR

    DEFF Research Database (Denmark)

    Skriver, Henning; Svendsen, Morten Thougaard; Nielsen, Flemming

    1999-01-01

    Polarimetric SAR-data of agricultural fields have been acquired by the Danish polarimetric L- and C-band SAR (EMISAR) during a number of missions at the Danish agricultural test site Foulum during 1995. The data are used to study the classification potential of polarimetric SAR data using...

  5. SYNERGY EFFECTS IN WORK TEAMS

    Directory of Open Access Journals (Sweden)

    Raluca C. ZOLTAN

    2014-06-01

    Full Text Available Today’s organization increasingly utilizes all kind of teams in order to surpass their competitors through flexibility, adaptability and innovation, features which are seen to characterize the teams. For this purpose, the concept of synergy in teams’ activity is often mentioned as the prime reason for which collective work is considered to be superior comparative with individual work. But what exactly does it mean? The present paper aims to shed some light on the concept of synergy in work teams and its positive effects, namely, the social consequences of collective work such as social compensation, social indispensability, social comparison, social identity, but also its negative effects, such as free-riding, social loafing and sucker effect. These are important group phenomena that managers should be aware of because they have a major impact on team performance, and consequently, on organization performance.

  6. An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus

    Directory of Open Access Journals (Sweden)

    Ian M. Mackay

    2017-12-01

    Full Text Available The human coronaviruses (CoV include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV—the Middle East Respiratory Syndrome (MERS-CoV—was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

  7. Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, Kanchan; Palaninathan, Satheesh; Alcantara, Joanna Maria Ortiz; Yi, Lillian Li; Guarino, Linda; Sacchettini, James C.; Kao, C. Cheng (TAM)

    2008-03-31

    The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA-processing enzymes that are unusual for RNA viruses, including Nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. We solved the structure of a catalytically inactive mutant version of Nsp15, which was crystallized as a hexamer. The structure contains unreported flexibility in the active site of each subunit. Substitutions in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at purines as well as pyrimidines. Mutations that targeted the residues involved in subunit interactions generally resulted in the formation of catalytically inactive monomers. The RNA-binding residues were mapped by a method linking reversible cross-linking, RNA affinity purification, and peptide fingerprinting. Alanine substitution of several residues in the RNA-contacting portion of Nsp15 did not affect hexamer formation but decreased the affinity of RNA binding and reduced endonuclease activity. This suggests a model for Nsp15 hexamer interaction with RNA.

  8. Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells

    International Nuclear Information System (INIS)

    Qin Zhaoling; Zhao Ping; Zhang Xiaolian; Yu Jianguo; Cao Mingmei; Zhao Lanjuan; Luan Jie; Qi Zhongtian

    2004-01-01

    Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and SARS-CoV S RNA transcripts were found significantly reduced, and the expression of SARS-CoV S glycoprotein was strongly inhibited in those cells co-transfected with either EGFP- or S-specific siRNAs. Our findings demonstrated that the S-specific siRNAs used in this study were able to specifically and effectively inhibit SARS-CoV S glycoprotein expression in cultured cells through blocking the accumulation of S mRNA, which may provide an approach for studies on the functions of SARS-CoV S gene and development of novel prophylactic or therapeutic agents for SARS-CoV

  9. Discovery of novel bat coronaviruses in south China that use the same receptor as MERS coronavirus.

    Science.gov (United States)

    Luo, Chu-Ming; Wang, Ning; Yang, Xing-Lou; Liu, Hai-Zhou; Zhang, Wei; Li, Bei; Hu, Ben; Peng, Cheng; Geng, Qi-Bin; Zhu, Guang-Jian; Li, Fang; Shi, Zheng-Li

    2018-04-18

    Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs, which belong to the same species as MERS-CoV, have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus HKU4 , Pipistrellus pipistrellus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io , from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein--protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs might have acquired their spike genes from a DPP4-recognizing bat HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV. IMPORTANCE Previous studies suggested that the Middle East respiratory syndrome coronavirus (MERS-CoV) may have originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses (BetaCoVs) in eight bat species. We provide the evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus HKU4. Our study expands the host

  10. [Surveillance on severe acute respiratory syndrome associated coronavirus in animals at a live animal market of Guangzhou in 2004].

    Science.gov (United States)

    Wang, Ming; Jing, Huai-qi; Xu, Hui-fang; Jiang, Xiu-gao; Kan, Biao; Liu, Qi-yong; Wan, Kang-lin; Cui, Bu-yun; Zheng, Han; Cui, Zhi-gang; Yan, Mei-ying; Liang, Wei-li; Wang, Hong-xia; Qi, Xiao-bao; Li, Zhen-jun; Li, Ma-chao; Chen, Kai; Zhang, En-min; Zhang, Shou-yin; Hai, Rong; Yu, Dong-zheng; Xu, Jian-guo

    2005-02-01

    To study the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV) like virus in animals at a live animal market of Guanzhou in 2004 before and after culling of wild animal action taken by the local authority, in order to predict the re-emerging of SARS from animal originals in this region. Animals at live animal market were sampled for rectal and throat swabs in triplicate. A single step realtime reverse transcription-polymerase chain reaction (RT-PCR) diagnostic kit was performed for screening SARS-CoV like virus, the manual nested RT- PCR and DNA sequencing were performed for confirmation. Only specimens which tested positive for both of the N and P genes by nested RT-PCR were scored as positive. In 31 animals sampled in January 5 2004 before culling of wild animals at Guangdong Province, including 20 cats (Felis catus), 5 red fox (Vulpes vulpes) and 6 Lesser rice field rats (Rattus losea), 8 (25.8%) animals were tested positive for SARS-CoV like virus by RT-PCR methods, of which 4 cats, 3 red fox and one Lesser rice field rats were included. However, two weeks after culling of animals and disinfection of the market were implemented, in 119 animals sampled in January 20 2004, including 6 rabbits (Oryctolagus cuniculus), 13 cats, 46 red jungle fowl (Gallus gallus), 13 spotbill duck (Anas platyrhynchos), 10 greylag goose (Anser anser), 31 Chinese francolin (Franclinus pintadeanus), only rectal swab from one greylag goose was tested positive for SARS-CoV like virus. Furthermore, in 102 animals that including 14 greylag gooses, 3 cats, 5 rabbits, 9 spotbill duck (Anaspoecilorhyncha), 2 Chinese francolin (Franclinus pintadeanus), 8 common pheasant (Phasianus colchicus), 6 pigeons, 9 Chinese muntjac (Muntiacus reevesi), 19 wild boar (Sus scrofa), 16 Lesser rice field rats, 5 dogs, 1 mink (Mustela vison), 3 goats, 2 green peafowl (Pavo muticus) sampled in April, May, June, July, August and November, only rectal swab from one pig was tested positive

  11. Data Analytics for SAR

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, David Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Calef, Matthew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-02

    We assess the ability of variants of anomalous change detection (ACD) to identify human activity associated with large outdoor music festivals as they are seen from synthetic aperture radar (SAR) imagery collected by the Sentinel-1 satellite constellation. We found that, with appropriate feature vectors, ACD using random-forest machine learning was most effective at identifying changes associated with the human activity.

  12. [Nosocomial infections due to human coronaviruses in the newborn].

    Science.gov (United States)

    Gagneur, A; Legrand, M C; Picard, B; Baron, R; Talbot, P J; de Parscau, L; Sizun, J

    2002-01-01

    Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive nasopharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

  13. Cross host transmission in the emergence of MERS coronavirus

    NARCIS (Netherlands)

    C.B.E.M. Reusken (Chantal); V.S. Raj (Stalin); M.P.G. Koopmans D.V.M. (Marion); B.L. Haagmans (Bart)

    2016-01-01

    textabstractCoronaviruses (CoVs) able to infect humans emerge through cross-host transmission from animals. There is substantial evidence that the recent Middle East respiratory syndrome (MERS)-CoV outbreak is fueled by zoonotic transmission from dromedary camels. This is largely based on the fact

  14. Tissue Distribution of the MERS-Coronavirus Receptor in Bats

    NARCIS (Netherlands)

    W. Widagdo; L. Begeman (Lineke); D. Schipper (Debby); P.R.W.A. van Run (Peter); Cunningham, A.A. (Andrew A); Kley, N. (Nils); C.B.E.M. Reusken (Chantal); B.L. Haagmans (Bart); J.M.A. van den Brand (Judith)

    2017-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor.The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism.Apart from

  15. Tissue Distribution of the MERS-Coronavirus Receptor in Bats

    NARCIS (Netherlands)

    Widagdo, W; Begeman, Lineke; Schipper, Debby; van Run, Peter R; Cunningham, Andrew A; Kley, Nils; Reusken, Chantal B E M; Haagmans, Bart L; van den Brand, Judith M A

    2017-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary

  16. Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus

    NARCIS (Netherlands)

    Vergara-Alert, Júlia; van den Brand, Judith M A; Widagdo, W; Muñoz, Marta; Raj, V Stalin; Schipper, Debby; Solanes, David; Cordón, Ivan; Bensaid, Albert; Haagmans, Bart L; Segalés, Joaquim

    Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs.

  17. Transmission of MERS-coronavirus in household contacts

    NARCIS (Netherlands)

    Drosten, Christian; Meyer, Benjamin; Müller, Marcel A; Corman, Victor M; Al-Masri, Malak; Hossain, Raheela; Madani, Hosam; Sieberg, Andrea; Bosch, Berend Jan|info:eu-repo/dai/nl/273306049; Lattwein, Erik; Alhakeem, Raafat F; Assiri, Abdullah M; Hajomar, Waleed; Albarrak, Ali M; Al-Tawfiq, Jaffar A; Zumla, Alimuddin I; Memish, Ziad A

    2014-01-01

    BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index

  18. Renin-angiotensin system in human coronavirus pathogenesis

    NARCIS (Netherlands)

    Wevers, Brigitte A.; van der Hoek, Lia

    2010-01-01

    Although initially considered relatively harmless pathogens, human coronaviruses (HCoVs) are nowadays known to be associated with more severe clinical complications. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified species HCoV-NL63

  19. Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers

    NARCIS (Netherlands)

    Cong, Yingying; Kriegenburg, Franziska; de Haan, Cornelis A. M.; Reggiori, Fulvio

    2017-01-01

    Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down

  20. Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing.

    Directory of Open Access Journals (Sweden)

    Lance D Eckerle

    2010-05-01

    Full Text Available Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN in nonstructural protein 14 (nsp14 of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication

  1. Bistatic SAR: Proof of Concept.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

    2014-10-01

    Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

  2. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Ratia, Kiira; Pegan, Scott; Takayama, Jun; Sleeman, Katrina; Coughlin, Melissa; Baliji, Surendranath; Chaudhuri, Rima; Fu, Wentao; Prabhakar, Bellur S.; Johnson, Michael E.; Baker, Susan C.; Ghosh, Arun K.; Mesecar, Andrew D. (Loyola); (Purdue); (UIC)

    2008-10-27

    We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and ISG15 conjugates and plays a significant role in helping SARS-CoV evade the human immune system. We screened a structurally diverse library of 50,080 compounds for inhibitors of PLpro and discovered a noncovalent lead inhibitor with an IC{sub 50} value of 20 {mu}M, which was improved to 600 nM via synthetic optimization. The resulting compound, GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an EC{sub 50} of 15 {mu}M and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site. These findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs.

  3. Coronavirus infection in mink (Mustela vison). Serological evidence of infection with a coronavirus related to transmissible gastroenteritis virus and porcine epidemic diarrhea virus

    DEFF Research Database (Denmark)

    Have, P; Moving, V; Svansson, V

    1992-01-01

    Antibodies to a transmissible gastroenteritis virus (TGEV)-related coronavirus have been demonstrated in mink sera by indirect immunofluorescence, peroxidase-linked antibody assays and immunoblotting. This is the first serological evidence of a specific coronavirus infection in mink. The putative...

  4. Toward a Formal Model of Cognitive Synergy

    OpenAIRE

    Goertzel, Ben

    2017-01-01

    "Cognitive synergy" refers to a dynamic in which multiple cognitive processes, cooperating to control the same cognitive system, assist each other in overcoming bottlenecks encountered during their internal processing. Cognitive synergy has been posited as a key feature of real-world general intelligence, and has been used explicitly in the design of the OpenCog cognitive architecture. Here category theory and related concepts are used to give a formalization of the cognitive synergy concept....

  5. Coronavirus-like particles in laboratory rabbits with different syndromes in The Netherlands (Coronavirus-like particles in rabbits).

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); J.S. Teppema; G. van Steenis (Bert)

    1982-01-01

    textabstractVirus-like particles were identified from the plasma of rabbits which developed pleural effusion disease after inoculation with different strains of Treponema pallidum. These particles were considered coronavirus-like on the basis of their size, morphology, and buoyant density. Clinical

  6. Infrastructures for healthcare: From synergy to reverse synergy.

    Science.gov (United States)

    Langhoff, Tue Odd; Amstrup, Mikkel Hvid; Mørck, Peter; Bjørn, Pernille

    2018-03-01

    The Danish General Practitioners Database has over more than a decade developed into a large-scale successful information infrastructure supporting medical research in Denmark. Danish general practitioners produce the data, by coding all patient consultations according to a certain set of classifications, on the entire Danish population. However, in the Autumn of 2014, the system was temporarily shut down due to a lawsuit filed by two general practitioners. In this article, we ask why and identify a political struggle concerning authority, control, and autonomy related to a transformation of the fundamental ontology of the information infrastructure. We explore how the transformed ontology created cracks in the inertia of the information infrastructure damaging the long-term sustainability. We propose the concept of reverse synergy as the awareness of negative impacts occurring when uncritically adding new actors or purposes to a system without due consideration to the nature of the infrastructure. We argue that while long-term information infrastructures are dynamic by nature and constantly impacted by actors joining or leaving the project, each activity of adding new actors must take reverse synergy into account, if not to risk breaking down the fragile nature of otherwise successful information infrastructures supporting research on healthcare.

  7. Bistatic sAR data processing algorithms

    CERN Document Server

    Qiu, Xiaolan; Hu, Donghui

    2013-01-01

    Synthetic Aperture Radar (SAR) is critical for remote sensing. It works day and night, in good weather or bad. Bistatic SAR is a new kind of SAR system, where the transmitter and receiver are placed on two separate platforms. Bistatic SAR is one of the most important trends in SAR development, as the technology renders SAR more flexible and safer when used in military environments. Imaging is one of the most difficult and important aspects of bistatic SAR data processing. Although traditional SAR signal processing is fully developed, bistatic SAR has a more complex system structure, so sign

  8. Cultural synergy in information institutions

    CERN Document Server

    Smiraglia, Richard P

    2014-01-01

    Cultural forces govern a synergistic relationship among information institutions that shapes their roles collectively and individually. Cultural synergy is the combination of perception- and behavior-shaping knowledge within, between, and among groups. Our hyperlinked era makes information-sharing among institutions critically important for scholarship as well as for the advancement of humankind. Information institutions are those that have, or share in, the mission to preserve, conserve, and disseminate information objects and their informative content. A central idea is the notion of social

  9. Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009-2012.

    Science.gov (United States)

    Sipulwa, Lenata A; Ongus, Juliette R; Coldren, Rodney L; Bulimo, Wallace D

    2016-02-01

    Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV-OC43 and three HCoV-229E. There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children.

  10. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  11. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.; Qian, Zhaohui; Holmes, Kathryn V.; Li, Fang (Cornell); (UMM-MED); (Colorado)

    2011-09-28

    Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.

  12. Synergy in RF Current Drive

    International Nuclear Information System (INIS)

    Dumont, R.J.; Giruzzi, G.

    2005-01-01

    Auxiliary methods for efficient non-inductive current drive in tokamaks generally involve the interaction of externally driven waves with superthermal electrons. Among the possible schemes, Lower Hybrid (LH) and Electron Cyclotron (EC) current drive have been so far the most successful. An interesting aspect of their combined use is the fact that since they involve possibly overlapping domains in velocity and configuration spaces, a synergy between them is expected for appropriate parameters. The signature of this effect, significant improvement of the EC current drive efficiency, results from a favorable interplay of the quasilinear diffusions induced by both waves. Recently, improvements of the EC current drive efficiency in the range of 2-4 have been measured in fully non-inductive discharges in the Tore Supra tokamak, providing the first clear evidence of this effect in steady-state conditions. We present here the experimental aspects of these discharges. The associated kinetic modeling and current state of understanding of the LH-EC synergy phenomenon are also discussed. (authors)

  13. Synergy in RF Current Drive

    International Nuclear Information System (INIS)

    Dumont, R.J.; Giruzzi, G.

    2005-01-01

    Auxiliary methods for efficient non-inductive current drive in tokamaks generally involve the interaction of externally driven waves with superthermal electrons. Among the possible schemes, Lower Hybrid (LH) and Electron Cyclotron (EC) current drive have been so far the most successful. An interesting aspect of their combined use is the fact that since they involve possibly overlapping domains in velocity and configuration spaces, a synergy between them is expected for appropriate parameters. The signature of this effect, significant improvement of the EC current drive efficiency, results from a favorable interplay of the quasilinear diffusions induced by both waves. Recently, improvements of the EC current drive efficiency in the range of 2-4 have been measured in fully non-inductive discharges in the Tore Supra tokamak, providing the first clear evidence of this effect in steady-state conditions. We present here the experimental aspects of these discharges. The associated kinetic modeling and current state of understanding of the LH-EC synergy phenomenon are also discussed

  14. Chimeric exchange of coronavirus nsp5 proteases (3CLpro) identifies common and divergent regulatory determinants of protease activity.

    Science.gov (United States)

    Stobart, Christopher C; Sexton, Nicole R; Munjal, Havisha; Lu, Xiaotao; Molland, Katrina L; Tomar, Sakshi; Mesecar, Andrew D; Denison, Mark R

    2013-12-01

    Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.

  15. Systematic synergy modeling: understanding drug synergy from a systems biology perspective.

    Science.gov (United States)

    Chen, Di; Liu, Xi; Yang, Yiping; Yang, Hongjun; Lu, Peng

    2015-09-16

    Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose-response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

  16. Differences between kinematic synergies and muscle synergies during two-digit grasping

    Directory of Open Access Journals (Sweden)

    Michele eTagliabue

    2015-03-01

    Full Text Available The large number of mechanical degrees of freedom of the hand is not fully exploited during actual movements such as grasping. Usually, angular movements in various joints tend to be coupled, and EMG activities in different hand muscles tend to be correlated. The occurrence of covariation in the former was termed kinematic synergies, in the latter muscle synergies. This study addresses two questions: (i Whether kinematic and muscle synergies can simultaneously accommodate for kinematic and kinetic constraints. (ii If so, whether there is an interrelation between kinematic and muscle synergies. We used a reach-grasp-and-pull paradigm and recorded the hand kinematics as well as 8 surface EMGs. Subjects had to either perform a precision grip or side grip and had to modify their grip force in order to displace an object against a low or high load. The analysis was subdivided into three epochs: reach, grasp-and-pull, and static hold. Principal component analysis (PCA, temporal or static was performed separately for all three epochs, in the kinematic and in the EMG domain. PCA revealed that (i Kinematic- and muscle-synergies can simultaneously accommodate kinematic (grip type and kinetic task constraints (load condition. (ii Upcoming grip and load conditions of the grasp are represented in kinematic- and muscle-synergies already during reach. Phase plane plots of the principal muscle-synergy against the principal kinematic synergy revealed (iii that the muscle-synergy is linked (correlated, and in phase advance to the kinematic synergy during reach and during grasp-and-pull. Furthermore (iv, pair-wise correlations of EMGs during hold suggest that muscle-synergies are (in part implemented by coactivation of muscles through common input. Together, these results suggest that kinematic synergies have (at least in part their origin not just in muscular activation, but in synergiestic muscle activation. In short: kinematic synergies may result from muscle

  17. Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-XL Protein▿

    Science.gov (United States)

    Tan, Ying-Xim; Tan, Timothy H. P.; Lee, Marvin J.-R.; Tham, Puay-Yoke; Gunalan, Vithiagaran; Druce, Julian; Birch, Chris; Catton, Mike; Fu, Nai Yang; Yu, Victor C.; Tan, Yee-Joo

    2007-01-01

    The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell lines. In this study, we show that the overexpression of Bcl-XL, a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-XL and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-XL was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-XL. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-XL are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-XL also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-XL at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments. PMID:17428862

  18. A rare cause of acute flaccid paralysis: Human coronaviruses

    OpenAIRE

    Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir

    2015-01-01

    Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common ...

  19. Prevalence of Korean cats with natural feline coronavirus infections

    Directory of Open Access Journals (Sweden)

    Lee Myoung-Heon

    2011-09-01

    Full Text Available Abstract Background Feline coronavirus is comprised of two pathogenic biotypes consisting of feline infectious peritonitis virus (FIPV and feline enteric coronavirus (FECV, which are both divided into two serotypes. To examine the prevalence of Korean cats infected with feline coronavirus (FCoV type I and II, fecal samples were obtained from 212 cats (107 pet and 105 feral in 2009. Results Fourteen cats were FCoV-positive, including infections with type I FCoV (n = 8, type II FCoV (n = 4, and types I and II co-infection (n = 2. Low seroprevalences (13.7%, 29/212 of FCoV were identified in chronically ill cats (19.3%, 16/83 and healthy cats (10.1%, 13/129. Conclusions Although the prevalence of FCoV infection was not high in comparison to other countries, there was a higher prevalence of type I FCoV in Korean felines. The prevalence of FCoV antigen and antibody in Korean cats are expected to gradually increase due to the rising numbers of stray and companion cats.

  20. Cultural Synergy and Organizational Change

    DEFF Research Database (Denmark)

    Strøbæk, Pernille Solveig; Vogt, Joachim

    2013-01-01

    This paper explores informal codes and rhythms of social behavior at work and their relation to organizational change and wellbeing. After a merger within a public service organization we organized 8 focus groups of 2-3 clerical or academic employees within a head office and a division office (N...... = 21). Word counts of ‘I’ and ‘we’ revealed that people sharing pre-merger organizational background (homogeneous groups) used ‘we’ more often than heterogeneous groups. Head office employees were concerned with workload and social code, whereas division office employees mainly discussed meetings......, commitment, and office space. Organizational background rather than office cultures guided these differences. We found that in a merged organization cultural synergies are possible to create if practical and social values for employees are offered. Thus, interesting new ways to transform problems...

  1. PHARUS : PHased ARray Universal SAR

    NARCIS (Netherlands)

    Paquay, M.H.A.; Vermeulen, B.C.B.; Koomen, P.J.; Hoogeboom, P.; Snoeij, P.; Pouwels, H.

    1996-01-01

    In the Netherlands, a polarimetric C-band aircraft SAR (Synthetic Aperture Radar) has been developed. The project is called PHARUS, an acronm for PHased ARray Universal SAR. This instrument serves remote sensing applications. The antenna system contains 48 active modules (expandable to 96). A module

  2. How infectious is SARS virus

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. How infectious is SARS virus. Influenza: 1 patient infects ten people. SARS: 1 patient infects 2-4 people. Incubation period 10 days. Are there `silent´ cases ? Is quarantine enough ? How will it behave if and when it returns ?

  3. Marine parameters from synergy of optical and radar satellite data

    Science.gov (United States)

    Lehner, S.; Hoja, D.; Schulz-Stellenfleth, J.

    In 2001 the European Space Agency ESA will launch the earth observation satellite ENVISAT. It will carry several instruments that provide new opportunities to measure oceanographic variables. Together, they represent the main measurement techniques of satellite oceanography, and complement each other in an ideal manner. These instruments are to be used in synergy to: Improve the analysis of measured wind and ocean wave fields, and thereby improve weather forecasting at weather centers; Determine the extent and variables of sea ice and develop a five-day sea ice prediction model, to support maritime shipping and offshore activities; Monitor and map sediment and suspended matter transport in coastal regions, especially in areas with large river estuaries, which greatly affects shipping lanes, harbors, and dredging activities; Monitor hydrobiological and bio-geochemical variables related to water quality in coastal regions and large inland waters, which affects ecology, coastal development, aquaculture, drinking water supplies, and tourism. To prepare the oceanographic community to make best use of the ENVISAT sensors in the pre-launch phase, existing algorithms to derive marine parameters are used and validated using data from the ERS SAR, the ERS RA, SeaWiFS and IRS MOS sensors now in operation. Derived products are used to address problems that can best be tackled using the synergy of radar and optical data, such as the effect of surface slicks on radar wind measurements, of sea state on ocean color, of wind and waves on the resuspension of suspended matter, and of wind and waves on sea ice variables.

  4. The coronavirus spike protein : mechanisms of membrane fusion and virion incorporation

    NARCIS (Netherlands)

    Bosch, B.J.

    2004-01-01

    The coronavirus spike protein is a membrane-anchored glycoprotein responsible for virus-cell attachment and membrane fusion, prerequisites for a successful virus infection. In this thesis, two aspects are described regarding the molecular biology of the coronavirus spike protein: its membrane fusion

  5. On the biased nucleotide composition of the human coronavirus RNA genome

    NARCIS (Netherlands)

    Berkhout, Ben; van Hemert, Formijn

    2015-01-01

    We investigated the nucleotide composition of the RNA genome of the six human coronaviruses. Some general coronavirus characteristics were apparent (e.g. high U, low C count), but we also detected species-specific signatures. Most strikingly, the high U and low C proportions are quite variable and

  6. Molecular epidemiology of bovine coronavirus on the basis of comparative analyses of the S gene

    DEFF Research Database (Denmark)

    Liu, Lihong; Hägglund, Sara; Hakhverdyan, Mikhayil

    2006-01-01

    Bovine coronavirus (BCoV), a group 2 member of the genus Coronavirus in the family Coronaviridae, is an important pathogen in cattle worldwide. It causes diarrhea in adult animals (winter dysentery), as well as enteric and respiratory diseases in calves. The annual occurrence of BCoV epidemics...

  7. Human Coronaviruses 229E and NL63: Close Yet Still So Far

    NARCIS (Netherlands)

    Dijkman, Ronald; van der Hoek, Lia

    2009-01-01

    HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence

  8. Bistatic SAR: Imagery & Image Products.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

    2014-10-01

    While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

  9. Isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14, from domestic rabbits.

    Science.gov (United States)

    Lau, Susanna K P; Woo, Patrick C Y; Yip, Cyril C Y; Fan, Rachel Y Y; Huang, Yi; Wang, Ming; Guo, Rongtong; Lam, Carol S F; Tsang, Alan K L; Lai, Kenneth K Y; Chan, Kwok-Hung; Che, Xiao-Yan; Zheng, Bo-Jian; Yuen, Kwok-Yung

    2012-05-01

    We describe the isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by reverse transcriptase PCR (RT-PCR), with a viral load of up to 10(8) copies/ml. RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic effects. Northern blotting confirmed the production of subgenomic mRNAs coding for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a transcription regulatory sequence, 5'-UCUAAAC-3'. Phylogenetic analysis showed that RbCoV HKU14 formed a distinct branch among Betacoronavirus subgroup A coronaviruses, being most closely related to but separate from the species Betacoronavirus 1. A comparison of the conserved replicase domains showed that RbCoV HKU14 possessed N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.

  10. Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease

    International Nuclear Information System (INIS)

    Erles, Kerstin; Toomey, Crista; Brooks, Harriet W.; Brownlie, Joe

    2003-01-01

    An investigation into the causes of canine infectious respiratory disease was carried out in a large rehoming kennel. Tissue samples taken from the respiratory tract of diseased dogs were tested for the presence of coronaviruses using RT-PCR with conserved primers for the polymerase gene. Sequence analysis of four positive samples showed the presence of a coronavirus with high similarity to both bovine and human coronavirus (strain OC43) in their polymerase and spike genes, whereas there was a low similarity to comparable genes in the enteric canine coronavirus. This canine respiratory coronavirus (CRCV) was detected by RT-PCR in 32/119 tracheal and 20/119 lung samples, with the highest prevalence being detected in dogs with mild clinical symptoms. Serological analysis showed that the presence of antibodies against CRCV on the day of entry into the kennel decreased the risk of developing respiratory disease

  11. Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

    Directory of Open Access Journals (Sweden)

    Gary R. Whittaker

    2012-06-01

    Full Text Available Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.

  12. Expression, purification and crystallization of the SARS-CoV macro domain

    International Nuclear Information System (INIS)

    Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre

    2006-01-01

    The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2 1 , with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å

  13. Expression, purification and crystallization of the SARS-CoV macro domain

    Energy Technology Data Exchange (ETDEWEB)

    Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre, E-mail: marie-pierre.egloff@afmb.univ-mrs.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, UMR 6098-Case 932, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

    2006-04-01

    The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å.

  14. Coronavirus minus-strand RNA synthesis and effect of cycloheximide on coronavirus RNA synthesis

    International Nuclear Information System (INIS)

    Sawicki, S.G.; Sawicki, D.L.

    1986-01-01

    The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fold-greater titers of infectious virus and delayed the detachment of cells from the monolayer which permitted viral RNA synthesis to be studied conveniently until at least 10 h postinfection. Seven species of poly(A)-containing viral RNAs were synthesized at early and late times infection, in nonequal but constant ratios. MHV minus-strand RNA synthesis was first detected at about 3 h after infection and was found exclusively in the viral replicative intermediates and was not detected in 60S single-stranded form in infected cells. Early in the replication cycle, from 45 to 65% of the [ 3 H]uridine pulse-labeled RF core of purified MHV replicative intermediates was in minus-strand RNA. The rate of minus-strand synthesis peaked at 5 to 6 h postinfection and then declined to about 20% of the maximum rate. The addition of cycloheximide before 3 h postinfection prevented viral RNA synthesis, whereas the addition of cycloheximide after viral RNA synthesis had begun resulted in the inhibition of viral RNA synthesis. The synthesis of both genome and subgenomic mRNAs and of viral minus strands required continued protein synthesis, and minis-strand RNA synthesis was three- to fourfold more sensitive to inhibition of cycloheximide than was plus-strand synthesis

  15. Synergy cycles in the Norwegian innovation system: The relation between synergy and cycle values

    OpenAIRE

    Inga Ivanova; Oivind Strand; Loet Leydesdorff

    2014-01-01

    The knowledge base of an economy measured in terms of Triple Helix relations can be analyzed in terms of mutual information among geographical, sectorial, and size distributions of firms as dimensions of the probabilistic entropy. The resulting synergy values of a TH system provide static snapshots. In this study, we add the time dimension and analyze the synergy dynamics using the Norwegian innovation system as an example. The synergy among the three dimensions can be mapped as a set of part...

  16. Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

    Science.gov (United States)

    Al-Mulla, Hawaa M N; Turrell, Lauren; Smith, Nicola M; Payne, Luke; Baliji, Surendranath; Züst, Roland; Thiel, Volker; Baker, Susan C; Siddell, Stuart G; Neuman, Benjamin W

    2014-04-01

    Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None

  17. Managing Tensions And Forging Creative Synergies Between ...

    African Journals Online (AJOL)

    Managing Tensions And Forging Creative Synergies Between Indigenous And Modern Settlement Planning Concepts And Practices: Lessons For The Design And Planning For Sustainable Settlements And Built-Forms In Southern Africa.

  18. Sensory Synergy as Environmental Input Integration

    Directory of Open Access Journals (Sweden)

    Fady eAlnajjar

    2015-01-01

    Full Text Available The development of a method to feed proper environmental inputs back to the central nervous system (CNS remains one of the challenges in achieving natural movement when part of the body is replaced with an artificial device. Muscle synergies are widely accepted as a biologically plausible interpretation of the neural dynamics between the CNS and the muscular system. Yet the sensorineural dynamics of environmental feedback to the CNS has not been investigated in detail. In this study, we address this issue by exploring the concept of sensory synergy. In contrast to muscle synergy, we hypothesize that sensory synergy plays an essential role in integrating the overall environmental inputs to provide low-dimensional information to the CNS. We assume that sensor synergy and muscle synergy communicate using these low-dimensional signals. To examine our hypothesis, we conducted posture control experiments involving lateral disturbance with 9 healthy participants. Proprioceptive information represented by the changes on muscle lengths were estimated by using the musculoskeletal model analysis software SIMM. Changes on muscles lengths were then used to compute sensory synergies. The experimental results indicate that the environmental inputs were translated into the two dimensional signals and used to move the upper limb to the desired position immediately after the lateral disturbance. Participants who showed high skill in posture control were found to be likely to have a strong correlation between sensory and muscle signaling as well as high coordination between the utilized sensory synergies. These results suggest the importance of integrating environmental inputs into suitable low-dimensional signals before providing them to the CNS. This mechanism should be essential when designing the prosthesis’ sensory system to make the controller simpler

  19. Coevolution: A synergy in biology and ecology

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2015-06-01

    Full Text Available Synergy refers to that in an open and complex system consisting of a large number of subsystems, far from equilibrium, its subsystems interact in a nonlinear way to produce synergistic effects and thus make the system generate a self-organization structure in space/time with certain functions. Biologists and ecologists, tend to use coevolution/coadaptation to represent the terminology "synergy". Coevolution and research methodology were briefly discussed in present paper.

  20. Sensory synergy as environmental input integration.

    Science.gov (United States)

    Alnajjar, Fady; Itkonen, Matti; Berenz, Vincent; Tournier, Maxime; Nagai, Chikara; Shimoda, Shingo

    2014-01-01

    The development of a method to feed proper environmental inputs back to the central nervous system (CNS) remains one of the challenges in achieving natural movement when part of the body is replaced with an artificial device. Muscle synergies are widely accepted as a biologically plausible interpretation of the neural dynamics between the CNS and the muscular system. Yet the sensorineural dynamics of environmental feedback to the CNS has not been investigated in detail. In this study, we address this issue by exploring the concept of sensory synergy. In contrast to muscle synergy, we hypothesize that sensory synergy plays an essential role in integrating the overall environmental inputs to provide low-dimensional information to the CNS. We assume that sensor synergy and muscle synergy communicate using these low-dimensional signals. To examine our hypothesis, we conducted posture control experiments involving lateral disturbance with nine healthy participants. Proprioceptive information represented by the changes on muscle lengths were estimated by using the musculoskeletal model analysis software SIMM. Changes on muscles lengths were then used to compute sensory synergies. The experimental results indicate that the environmental inputs were translated into the two dimensional signals and used to move the upper limb to the desired position immediately after the lateral disturbance. Participants who showed high skill in posture control were found to be likely to have a strong correlation between sensory and muscle signaling as well as high coordination between the utilized sensory synergies. These results suggest the importance of integrating environmental inputs into suitable low-dimensional signals before providing them to the CNS. This mechanism should be essential when designing the prosthesis' sensory system to make the controller simpler.

  1. Rapid detection of MERS coronavirus-like viruses in bats: pote1ntial for tracking MERS coronavirus transmission and animal origin.

    Science.gov (United States)

    Woo, Patrick C Y; Lau, Susanna K P; Chen, Yixin; Wong, Emily Y M; Chan, Kwok-Hung; Chen, Honglin; Zhang, Libiao; Xia, Ningshao; Yuen, Kwok-Yung

    2018-03-07

    Recently, we developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for diagnosis of MERS coronavirus (MERS-CoV) in humans and dromedary camels. In this study, we examined the usefulness of this assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 (Ty-BatCoV-HKU4) RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19.0%) of 21 Pipistrellus bat CoV HKU5 (Pi-BatCoV-HKU5) RNA-positive alimentary samples of Pipistrellus abramus. There was significantly more Ty-BatCoV-HKU4 RNA-positive alimentary samples than Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive by the rapid MERS-CoV nucleocapsid protein detection assay (P < 0.001 by Chi-square test). The rapid assay was tested negative in all 51 alimentary samples RNA-positive for alphacoronaviruses (Rhinolophus bat CoV HKU2, Myotis bat CoV HKU6, Miniopterus bat CoV HKU8 and Hipposideros batCoV HKU10) and 32 alimentary samples positive for lineage B (SARS-related Rhinolophus bat CoV HKU3) and lineage D (Rousettus bat CoV HKU9) betacoronaviruses. No significant difference was observed between the viral loads of Ty-BatCoV-HKU4/Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive and negative by the rapid test (Mann-Witney U test). The rapid MERS-CoV nucleocapsid protein detection assay is able to rapidly detect lineage C betacoronaviruses in bats. It detected significantly more Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5 because MERS-CoV is more closely related to Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5. This assay will facilitate rapid on-site mass screening of animal samples for ancestors of MERS-CoV and tracking transmission in the related bat species.

  2. Coordinate induction of IFN-α and -γ by SARS-CoV also in the absence of virus replication

    International Nuclear Information System (INIS)

    Castilletti, Concetta; Bordi, Licia; Lalle, Eleonora; Rozera, Gabriella; Poccia, Fabrizio; Agrati, Chiara; Abbate, Isabella; Capobianchi, Maria R.

    2005-01-01

    Background:: Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV, characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication. This study is aimed at investigating the capability of SARS-CoV to activate IFN-α and -γ expression in lymphomonocytes (PBMC) from healthy donors, evaluating whether viral replication is necessary for this activation. Results:: SARS-CoV virus is able to induce both IFN-α and -γ mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being the most effective. The time course curve indicated that IFN-α mRNA induction peaked at 24 h.p.i,. whereas IFN-γ mRNA was still increasing at 48 h.p.i. Released IFN (both types) reached a plateau after 24-48 h.p.i. and remained rather stable over a 5-day period. A transient peak of negative strand viral RNA was detected after 1-2 days of infection, but neither infectious virus progeny yield nor newly produced viral genomic RNA could be evidenced in infected cultures, even after prolonged observation time (up to 13 days). Cocultivation of PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than exposure to live virus in eliciting IFN-α and -γ induction. A combination of IFN-α and -γ strongly inhibited SARS-CoV replication in Vero cells, while the single cytokines were much less effective. Conclusions:: This study provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate induction of IFN-α and -γ gene expression. Virus replication is not necessary for IFN induction since efficient IFN expression could be obtained also by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells. Concomitant activation of IFN-α and -γ gene expression by SARS-CoV in vivo may be relevant for the pathogenesis of the disease, both for the possible

  3. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

    Directory of Open Access Journals (Sweden)

    Damon Deming

    2006-12-01

    Full Text Available In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge.Using Venezuelan equine encephalitis virus replicon particles (VRP expressing the 2003 epidemic Urbani SARS-CoV strain spike (S glycoprotein (VRP-S or the nucleocapsid (N protein from the same strain (VRP-N, we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic

  4. The Paradox of Feline Coronavirus Pathogenesis: A Review

    Directory of Open Access Journals (Sweden)

    Luciana Wanderley Myrrha

    2011-01-01

    Full Text Available Feline coronavirus (FCoV is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP. Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.

  5. Greenhouses and their humanizing synergies

    Science.gov (United States)

    Haeuplik-Meusburger, Sandra; Paterson, Carrie; Schubert, Daniel; Zabel, Paul

    2014-03-01

    Greenhouses in space will require advanced technical systems of automatic watering, soil-less cultivation, artificial lighting, and computerized observation of plants. Functions discussed for plants in space habitats include physical/health requirements and human psychology, social cohesion, as well as the complex sensorial benefits of plants for humans. The authors consider the role of plants in long-term space missions historically since 1971 (Salyut 1) and propose a set of priorities to be considered within the design requirements for greenhouses and constructed environments given a range of benefits associated with plant-human relationships. They cite recent research into the use of greenhouses in extreme environments to reveal the relative importance of greenhouses for people living in isolated locations. Additionally, they put forward hypotheses about where greenhouses might factor into several strata of human health. In a recent design-in-use study of astronauts' experiences in space habitats discussed in Architecture for Astronauts (Springer Press 2011) it was found that besides the basic advantages for life support there are clearly additional "side benefits" for habitability and physical wellbeing, and thus long-term mission success. The authors have composed several key theses regarding the need to promote plant-human relationships in space, including areas where synergy and symbiosis occur. They cite new comprehensive research into the early US Space Program to reveal where programmatic requirements could be added to space architecture to increase the less quantifiable benefits to astronauts of art, recreation, and poetic engagement with their existential condition of estrangement from the planet. Specifically in terms of the technological requirements, the authors propose the integration of a new greenhouse subsystem component into space greenhouses—the Mobile Plant Cultivation Subsystem—a portable, personal greenhouse that can be integrated

  6. SAR calculation using FDTD simulations

    OpenAIRE

    Ferro, Francisco Nabais; Pinto, Guilherme Taveira; Pinho, Pedro

    2009-01-01

    The main intend of this work, is to determinate the Specific Absorption Rate (SAR) on human head tissues exposed to radiation caused by sources of 900 and 1800MHz, since those are the typical frequencies for mobile communications systems nowadays. In order to determinate the SAR, has been used the FDTD (Finite Difference Time Domain), which is a numeric method in time domain, obtained from the Maxwell equations in differential mode. In order to do this, a computational model from the human he...

  7. Ribonucleocapsid Formation of SARS-COV Through Molecular Action of the N-Terminal Domain of N Protein

    Energy Technology Data Exchange (ETDEWEB)

    Saikatendu, K.S.; Joseph, J.S.; Subramanian, V.; Neuman, B.W.; Buchmeier, M.J.; Stevens, R.C.; Kuhn, P.; /Scripps Res. Inst.

    2007-07-12

    Conserved amongst all coronaviruses are four structural proteins, the matrix (M), small envelope (E) and spike (S) that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in their lumen. The N terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C-terminus of N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17A (monoclinic) and 1.85 A (cubic) respectively, solved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the beta-sheet core. The functionally important positively charged beta-hairpin protrudes out of the core and is oriented similar to that in the IBV N-NTD and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggest a common mode of RNA recognition, but probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs hints that they employ different modes of both RNA recognition as well as oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.

  8. Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

    Science.gov (United States)

    Suderman, M. T.; McCarthy, M.; Mossell, E.; Watts, D. M.; Peters, C. J.; Shope, R.; Goodwin, T. J.

    2006-01-01

    A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

  9. Mechanism for Controlling the Dimer-Monomer Switch and Coupling Dimerization to Catalysis of the Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease

    Energy Technology Data Exchange (ETDEWEB)

    Shi,J.; Sivaraman, J.; Song, J.

    2008-01-01

    Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 Angstroms . Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 310-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.

  10. Crystal structure of Middle East respiratory syndrome coronavirus helicase.

    Directory of Open Access Journals (Sweden)

    Wei Hao

    2017-06-01

    Full Text Available Middle East respiratory syndrome coronavirus (MERS-CoV remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.

  11. Coronavirus envelope (E) protein remains at the site of assembly

    International Nuclear Information System (INIS)

    Venkatagopalan, Pavithra; Daskalova, Sasha M.; Lopez, Lisa A.; Dolezal, Kelly A.; Hogue, Brenda G.

    2015-01-01

    Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly. - Highlights: • Mouse hepatitis coronavirus (MHV-CoV) E protein localizes in the ERGIC and Golgi. • MHV-CoV E does not transport to the cell surface. • MHV-CoV can be genetically engineered with a tetracysteine tag appended to E. • First FRAP and correlative light electron microscopy of a CoV E protein. • Live-cell imaging shows that E is mobile in ERGIC/Golgi membranes

  12. Vacuolating encephalitis in mice infected by human coronavirus OC43

    International Nuclear Information System (INIS)

    Jacomy, Helene; Talbot, Pierre J.

    2003-01-01

    Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals

  13. Pathogenic characteristics of persistent feline enteric coronavirus infection in cats

    Science.gov (United States)

    Vogel, Liesbeth; Van der Lubben, Mariken; Te Lintelo, Eddie G.; Bekker, Cornelis P.J.; Geerts, Tamara; Schuijff, Leontine S.; Grinwis, Guy C.M.; Egberink, Herman F.; Rottier, Peter J.M.

    2010-01-01

    Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed. PMID:20663472

  14. Coronavirus envelope (E) protein remains at the site of assembly

    Energy Technology Data Exchange (ETDEWEB)

    Venkatagopalan, Pavithra [The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287-5401 (United States); School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401 (United States); Microbiology Graduate Program, Arizona State University, Tempe, AZ 85287-5401 (United States); Daskalova, Sasha M. [The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287-5401 (United States); Department of Biochemistry and Chemistry, Arizona State University, Tempe, AZ 85287-5401 (United States); Lopez, Lisa A. [The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287-5401 (United States); School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401 (United States); Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, AZ 85287-5401 (United States); Dolezal, Kelly A. [The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287-5401 (United States); School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401 (United States); Microbiology Graduate Program, Arizona State University, Tempe, AZ 85287-5401 (United States); Hogue, Brenda G., E-mail: Brenda.Hogue@asu.edu [The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287-5401 (United States); School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401 (United States)

    2015-04-15

    Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly. - Highlights: • Mouse hepatitis coronavirus (MHV-CoV) E protein localizes in the ERGIC and Golgi. • MHV-CoV E does not transport to the cell surface. • MHV-CoV can be genetically engineered with a tetracysteine tag appended to E. • First FRAP and correlative light electron microscopy of a CoV E protein. • Live-cell imaging shows that E is mobile in ERGIC/Golgi membranes.

  15. What is missing? An operational inundation mapping framework by SAR data

    Science.gov (United States)

    Shen, X.; Anagnostou, E. N.; Zeng, Z.; Kettner, A.; Hong, Y.

    2017-12-01

    Compared to optical sensors, synthetic aperture radar (SAR) works all-day all-weather. In addition, its spatial resolution does not decrease with the height of the platform and is thus applicable to a range of important studies. However, existing studies did not address the operational demands of real-time inundation mapping. The direct proof is that no water body product exists for any SAR-based satellites. Then what is missing between science and products? Automation and quality. What makes it so difficult to develop an operational inundation mapping technique based on SAR data? Spectrum-wise, unlike optical water indices such as MNDWI, AWEI etc., where a relative constant threshold may apply across acquisition of images, regions and sensors, the threshold to separate water from non-water pixels in each SAR images has to be individually chosen. The optimization of the threshold is the first obstacle to the automation of the SAR data algorithm. Morphologically, the quality and reliability of the results have been compromised by over-detection caused by smooth surface and shadowing area, the noise-like speckle and under-detection caused by strong-scatter disturbance. In this study, we propose a three-step framework that addresses all aforementioned issues of operational inundation mapping by SAR data. The framework consists of 1) optimization of Wishart distribution parameters of single/dual/fully-polarized SAR data, 2) morphological removal of over-detection, and 3) machine-learning based removal of under-detection. The framework utilizes not only the SAR data, but also the synergy of digital elevation model (DEM), and optical sensor-based products of fine resolution, including the water probability map, land cover classification map (optional), and river width. The framework has been validated throughout multiple areas in different parts of the world using different satellite SAR data and globally available ancillary data products. Therefore, it has the potential

  16. Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Gralinski, Lisa E.; Mitchell, Hugh D.; Dinnon, Kenneth H.; Leist, Sarah R.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Stratton, Kelly G.; Cockrell, Adam S.; Debbink, Kari; Sims, Amy C.; Waters, Katrina M.; Baric, Ralph S.; Fernandez-Sesma, Ana

    2017-11-15

    ABSTRACT

    Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2'O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures andin vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2'O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting.

    IMPORTANCECoronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that

  17. Robustness of muscle synergies during visuomotor adaptation

    Directory of Open Access Journals (Sweden)

    Reinhard eGentner

    2013-09-01

    Full Text Available During visuomotor adaptation a novel mapping between visual targets and motor commands is gradually acquired. How muscle activation patterns are affected by this process is an open question. We tested whether the structure of muscle synergies is preserved during adaptation to a visuomotor rotation. Eight subjects applied targeted isometric forces on a handle instrumented with a force transducer while electromyographic (EMG activity was recorded from 13 shoulder and elbow muscles. The recorded forces were mapped into horizontal displacements of a virtual sphere with simulated mass, elasticity, and damping. The task consisted of moving the sphere to a target at one of eight equally spaced directions. Subjects performed three baseline blocks of 32 trials, followed by six blocks with a 45° CW rotation applied to the planar force, and finally three wash-out blocks without the perturbation. The sphere position at 100 ms after movement onset revealed significant directional error at the beginning of the rotation, a gradual learning in subsequent blocks, and aftereffects at the beginning of the wash-out. The change in initial force direction was closely related to the change in directional tuning of the initial EMG activity of most muscles. Throughout the experiment muscle synergies extracted using a non-negative matrix factorization algorithm from the muscle patterns recorded during the baseline blocks could reconstruct the muscle patterns of all other blocks with an accuracy significantly higher than chance indicating structural robustness. In addition, the synergies extracted from individual blocks remained similar to the baseline synergies throughout the experiment. Thus synergy structure is robust during visuomotor adaptation suggesting that changes in muscle patterns are obtained by rotating the directional tuning of the synergy recruitment.

  18. Muscle synergy space: learning model to create an optimal muscle synergy.

    Science.gov (United States)

    Alnajjar, Fady; Wojtara, Tytus; Kimura, Hidenori; Shimoda, Shingo

    2013-01-01

    Muscle redundancy allows the central nervous system (CNS) to choose a suitable combination of muscles from a number of options. This flexibility in muscle combinations allows for efficient behaviors to be generated in daily life. The computational mechanism of choosing muscle combinations, however, remains a long-standing challenge. One effective method of choosing muscle combinations is to create a set containing the muscle combinations of only efficient behaviors, and then to choose combinations from that set. The notion of muscle synergy, which was introduced to divide muscle activations into a lower-dimensional synergy space and time-dependent variables, is a suitable tool relevant to the discussion of this issue. The synergy space defines the suitable combinations of muscles, and time-dependent variables vary in lower-dimensional space to control behaviors. In this study, we investigated the mechanism the CNS may use to define the appropriate region and size of the synergy space when performing skilled behavior. Two indices were introduced in this study, one is the synergy stability index (SSI) that indicates the region of the synergy space, the other is the synergy coordination index (SCI) that indicates the size of the synergy space. The results on automatic posture response experiments show that SSI and SCI are positively correlated with the balance skill of the participants, and they are tunable by behavior training. These results suggest that the CNS has the ability to create optimal sets of efficient behaviors by optimizing the size of the synergy space at the appropriate region through interacting with the environment.

  19. Identification of Aminopeptidase N as a Cellular Receptor for Human Coronavirus-229E

    Science.gov (United States)

    1992-05-12

    hemagglutinating encephalomyelitis virus (HEV), canine coronavirus (CCV), cat FIPV and feline enteric corona virus (FECV), human CVLPs, mouse...While the cat , dog and pig serve as natural hosts for the other coronavirus group 1 viruses , feline infectious peritonitis virus (FIPV), canine...3 2 . Virus Receptors ••••••••.••••••.....•................ 20 3. Viruses Which Cause Common Colds

  20. Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency

    OpenAIRE

    Szczawinska‐Poplonyk, Aleksandra; Jonczyk‐Potoczna, Katarzyna; Breborowicz, Anna; Bartkowska‐Sniatkowska, Alicja; Figlerowicz, Magdalena

    2012-01-01

    Please cite this paper as: Szczawinska‐Poplonyk et al. (2012) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12059. Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high‐risk patients with underlying conditions, particularl...

  1. Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia

    OpenAIRE

    Amer, Alazawy; Siti Suri, Arshad; Abdul Rahman, Omar; Mohd, Hair Bejo; Faruku, Bande; Saeed, Sharif; Tengku Azmi, Tengku Ibrahim

    2012-01-01

    Abstract Background Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first...

  2. Wave directional spectrum from SAR imagery

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

    Gaussian smoothed SAR image spectra have been evaluated from 512 x 512 pixel subscenes of image mode ERS-1 SAR scenes off Goa, Visakhapatnam, Paradeep and Portugal. The two recently acquired scenes off Portugal showed the signature of swell...

  3. Novel Polarimetric SAR Interferometry Algorithms, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Polarimetric radar interferometry (PolInSAR) is a new SAR imaging mode that is rapidly becoming an important technique for bare earth topographic mapping, tree...

  4. Crystal Structure of a Monomeric Form of Severe Acute Respiratory Syndrome Coronavirus Endonuclease Nsp15 Suggests a Role for Hexamerization As An Allosteric Switch

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, J.S.; Saikatendu, K.S.; Subramanian, V.; Neuman, B.W.; Buchmeier, M.J.; Stevens, R.C.; Kuhn, P.; /Scripps Res. Inst.

    2007-07-09

    Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn{sup 2+}-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335) determined to a resolution of 2.9 Angstroms. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by {approx}120 degrees into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.

  5. SAR matrices: automated extraction of information-rich SAR tables from large compound data sets.

    Science.gov (United States)

    Wassermann, Anne Mai; Haebel, Peter; Weskamp, Nils; Bajorath, Jürgen

    2012-07-23

    We introduce the SAR matrix data structure that is designed to elucidate SAR patterns produced by groups of structurally related active compounds, which are extracted from large data sets. SAR matrices are systematically generated and sorted on the basis of SAR information content. Matrix generation is computationally efficient and enables processing of large compound sets. The matrix format is reminiscent of SAR tables, and SAR patterns revealed by different categories of matrices are easily interpretable. The structural organization underlying matrix formation is more flexible than standard R-group decomposition schemes. Hence, the resulting matrices capture SAR information in a comprehensive manner.

  6. Human synergy in the rotten banana

    DEFF Research Database (Denmark)

    Svensson, Christian Franklin

    Counter-activity and synergy canbe viewed as a renaissance when recapturing the human potentials in civil society. The paper discusses employees' navigations and their imaginings of the future both relating to social enterprises and civil society and relating to the municipality as a rural area....

  7. The effect of aging on respiratory synergy.

    Science.gov (United States)

    Kweon, Migyoung; Son, Sung Min; Kwon, Yong Hyun

    2015-04-01

    [Purpose] The purpose of this study was to investigate the effect of aging on respiratory synergy, through the comparison of an elderly group and a young group, to help further understanding of postural control in the elderly. [Subjects and Methods] Ten community-dwelling elderly subjects and ten young subjects performed standing under two different respiratory conditions: quiet breathing and apnea. Center of foot pressure displacement and joint angular movements of the head, trunk, pelvis, hips, knees and ankles were measured. [Results] The results of this study showed that the elderly group had a respiratory synergy different from that of the young group. The elderly group in quiet stance used significantly more hip and pelvis movements when compensating for respiratory disturbance than standing with apnea, while the young group used significantly more whole body segments. There were no differences in angular displacements in the quiet stance between the elderly and the young groups. [Conclusion] The elderly group demonstrated a respiratory synergy pattern different from that of the young group. The findings indicate that aging changes the respiratory synergy pattern and this change is not due to decreased functioning of the ankle joint alone.

  8. IT Portfolio Selection and IT Synergy

    Science.gov (United States)

    Cho, Woo Je

    2010-01-01

    This dissertation consists of three chapters. The primary objectives of this dissertation are: (1) to provide a methodological framework of IT (Information Technology) portfolio management, and (2) to identify the effect of IT synergy on IT portfolio selection of a firm. The first chapter presents a methodological framework for IT project…

  9. Synergy between phenothiazines and oxacillin against clinical ...

    African Journals Online (AJOL)

    Methods: Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and oxacillin was investigated using Checkerboard (microbroth dilution) technique. Results: We found that all S. aureus strains, regardless of their susceptibility to oxacillin, ...

  10. Synergy between indigenous knowledge systems, modern health ...

    African Journals Online (AJOL)

    ... the people of this country should harness a synergy between indigenous health care systems, scientific research and modern health care methods. This article attempts to address the historical evolution of health care methods in South Africa, its effect on the community as well as challenges facing the health professions.

  11. Synergies between nonproliferation regimes: A pragmatic approach

    International Nuclear Information System (INIS)

    Findlay, Trevor; Meier, Oliver

    2001-01-01

    Full text: With the recent progress in establishing international nonproliferation regimes, the question of synergies between different verification and monitoring regimes is becoming more acute. Three multilateral and universal nonproliferation organisations covering safeguards on civil nuclear materials, nuclear testing, and chemical weapons are up and running. A regime on biological weapons is under negotiation. Several regional organisations concerned with monitoring nonproliferation commitments in the nuclear field are in place; others are being established. Past discussions on synergies between these regimes have suffered from being too far-reaching. These discussions often have not reflected adequately the political difficulties of cooperation between regimes with different membership, scope and institutional set-up. This paper takes a pragmatic look at exploiting synergies and identifies some potential and real overlaps in the work between different verification regimes. It argues for a bottom-up approach and identifies building blocks for collaboration between verification regimes. By realising such, more limited potential for cooperation, the ground could be prepared for exploiting other synergies between these regimes. (author)

  12. Convolutional Neural Networks for SAR Image Segmentation

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Nobel-Jørgensen, Morten

    2015-01-01

    Segmentation of Synthetic Aperture Radar (SAR) images has several uses, but it is a difficult task due to a number of properties related to SAR images. In this article we show how Convolutional Neural Networks (CNNs) can easily be trained for SAR image segmentation with good results. Besides...

  13. Precision Rectification of Airborne SAR Image

    DEFF Research Database (Denmark)

    Dall, Jørgen; Liao, M.; Zhang, Zhe

    1997-01-01

    A simple and direct procedure for the rectification of a certain class of airborne SAR data is presented. The relief displacements of SAR data are effectively removed by means of a digital elevation model and the image is transformed to the ground coordinate system. SAR data from the Danish EMISAR...

  14. Novel coronavirus and astrovirus in Delaware Bay shorebirds.

    Directory of Open Access Journals (Sweden)

    Kirsi S Honkavuori

    Full Text Available Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds.Analysis of shorebird fecal samples indicated the presence of a novel astrovirus and coronavirus. A sanderling sample yielded sequences with distant homology to avian nephritis virus 1, an astrovirus associated with acute nephritis in poultry. A ruddy turnstone sample yielded sequences with homology to deltacoronaviruses.Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.

  15. Muscle Synergy-Driven Robust Motion Control.

    Science.gov (United States)

    Min, Kyuengbo; Iwamoto, Masami; Kakei, Shinji; Kimpara, Hideyuki

    2018-04-01

    Humans are able to robustly maintain desired motion and posture under dynamically changing circumstances, including novel conditions. To accomplish this, the brain needs to optimize the synergistic control between muscles against external dynamic factors. However, previous related studies have usually simplified the control of multiple muscles using two opposing muscles, which are minimum actuators to simulate linear feedback control. As a result, they have been unable to analyze how muscle synergy contributes to motion control robustness in a biological system. To address this issue, we considered a new muscle synergy concept used to optimize the synergy between muscle units against external dynamic conditions, including novel conditions. We propose that two main muscle control policies synergistically control muscle units to maintain the desired motion against external dynamic conditions. Our assumption is based on biological evidence regarding the control of multiple muscles via the corticospinal tract. One of the policies is the group control policy (GCP), which is used to control muscle group units classified based on functional similarities in joint control. This policy is used to effectively resist external dynamic circumstances, such as disturbances. The individual control policy (ICP) assists the GCP in precisely controlling motion by controlling individual muscle units. To validate this hypothesis, we simulated the reinforcement of the synergistic actions of the two control policies during the reinforcement learning of feedback motion control. Using this learning paradigm, the two control policies were synergistically combined to result in robust feedback control under novel transient and sustained disturbances that did not involve learning. Further, by comparing our data to experimental data generated by human subjects under the same conditions as those of the simulation, we showed that the proposed synergy concept may be used to analyze muscle synergy

  16. Team synergies in sport: Theory and measures

    Directory of Open Access Journals (Sweden)

    Duarte Araújo

    2016-09-01

    Full Text Available Individual players act as a coherent unit during team sports performance, forming a team synergy. A synergy is a collective property of a task-specific organization of individuals, such that the degrees of freedom of each individual in the system are coupled, enabling the degrees of freedom of different individuals to co-regulate each other. Here, we present an explanation for the emergence of such collective behaviors, indicating how these can be assessed and understood through the measurement of key system properties that exist, considering the contribution of each individual and beyond These include: to (i dimensional compression, a process resulting in independent degree of freedom being coupled so that the synergy has fewer degrees of freedom than the set of components from which it arises; (ii reciprocal compensation, if one element do not produce its function, other elements should display changes in their contributions so that task goals are still attained; (iii interpersonal linkages, the specific contribution of each element to a group task; and (iv, degeneracy, structurally different components performing a similar, but not necessarily identical, function with respect to context. A primary goal of our analysis is to highlight the principles and tools required to understand coherent and dynamic team behaviors, as well as the performance conditions that make such team synergies possible, through perceptual attunement to shared affordances in individual performers. A key conclusion is that teams can be trained to perceive how to use and share specific affordances, explaining how individual’s behaviours self-organize into a group synergy.Ecological dynamics explanations of team behaviors can transit beyond mere ratification of sport performance, providing a comprehensive conceptual framework to guide the implementation of diagnostic measures by sport scientists, sport psychologists and performance analysts.

  17. Discovery of a novel bottlenose dolphin coronavirus reveals a distinct species of marine mammal coronavirus in Gammacoronavirus.

    Science.gov (United States)

    Woo, Patrick C Y; Lau, Susanna K P; Lam, Carol S F; Tsang, Alan K L; Hui, Suk-Wai; Fan, Rachel Y Y; Martelli, Paolo; Yuen, Kwok-Yung

    2014-01-01

    While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (Tursiops aduncus), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22-positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 × 10(3) to 1 × 10(5) copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (Ks) to the number of nonsynonymous substitutions per nonsynonymous site (Ka) in multiple regions of the genome, especially the S gene (Ka/Ks ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species, Cetacean coronavirus, in Gammacoronavirus, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species, Avian coronavirus, in Gammacoronavirus.

  18. Polarimetric scattering and SAR information retrieval

    CERN Document Server

    Jin, Ya-Qiu

    2013-01-01

    Taking an innovative look at Synthetic Aperture Radar (SAR), this practical reference fully covers new developments in SAR and its various methodologies and enables readers to interpret SAR imagery An essential reference on polarimetric Synthetic Aperture Radar (SAR), this book uses scattering theory and radiative transfer theory as a basis for its treatment of topics. It is organized to include theoretical scattering models and SAR data analysis techniques, and presents cutting-edge research on theoretical modelling of terrain surface. The book includes quantitative app

  19. Stalking SARS: CDC at Work

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about the SARS outbreak and how CDC worked to solve the mystery.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  20. Motor synergies and the equilibrium-point hypothesis.

    Science.gov (United States)

    Latash, Mark L

    2010-07-01

    The article offers a way to unite three recent developments in the field of motor control and coordination: (1) The notion of synergies is introduced based on the principle of motor abundance; (2) The uncontrolled manifold hypothesis is described as offering a computational framework to identify and quantify synergies; and (3) The equilibrium-point hypothesis is described for a single muscle, single joint, and multijoint systems. Merging these concepts into a single coherent scheme requires focusing on control variables rather than performance variables. The principle of minimal final action is formulated as the guiding principle within the referent configuration hypothesis. Motor actions are associated with setting two types of variables by a controller, those that ultimately define average performance patterns and those that define associated synergies. Predictions of the suggested scheme are reviewed, such as the phenomenon of anticipatory synergy adjustments, quick actions without changes in synergies, atypical synergies, and changes in synergies with practice. A few models are briefly reviewed.

  1. Dietary antioxidant synergy in chemical and biological systems.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2017-07-24

    Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

  2. Sensors and OBIA synergy for operational monitoring of surface water

    Science.gov (United States)

    Masson, Eric; Thenard, Lucas

    2010-05-01

    , frequent drought period and now with foreseen climate change impacts. This third case will demonstrate the efficiency of SPOT 5 programming in synergy with OBIA methodology to assess the evolution of dam surface water within a complete water cycle (i.e. 2008-09). In all those three cases image segmentation and classification algorithms developed with e-Cognition 8 software allow an easy to use implementation of simple to highly sophisticate OBIA rulsets fully operational in batch processes. Finally this contribution foresees the new opportunity of integration of Worldview 2 multispectral imagery (i.e. 8 bands) including its "coastal" band that will also find an application in continental surface water bathymetry. Worldview 2 is a recently launch satellite (e.g. October 2009) that starts to collect earth observation data since January 2010. It is therefore a promising new remote sensing tool to develop operational hydrology in combination high resolution SAR imagery and OBIA methodology. This contribution will conclude on the strong potential for operationalisation in hydrology and water resources management that recent and future sensors and image analysis methodologies are offering to water management and decision makers.

  3. Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation

    International Nuclear Information System (INIS)

    Yeung, Y.-S.; Yip, C.-W.; Hon, C.-C.; Chow, Ken Y.C.; Ma, Iris C.M.; Zeng Fanya; Leung, Frederick C.C.

    2008-01-01

    We have previously demonstrated that over-expression of spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) or its C-terminal subunit (S2) is sufficient to induce apoptosis in vitro. To further investigate the possible roles of S2 in SARS-CoV-induced apoptosis and pathogenesis of SARS, we characterized the host expression profiles induced upon S2 over-expression in Vero E6 cells by oligonucleotide microarray analysis. Possible activation of mitochondrial apoptotic pathway in S2 expressing cells was suggested, as evidenced by the up-regulation of cytochrome c and down-regulation of the Bcl-2 family anti-apoptotic members. Inhibition of Bcl-2-related anti-apoptotic pathway was further supported by the diminution of S2-induced apoptosis in Vero E6 cells over-expressing Bcl-xL. In addition, modulation of CCN E2 and CDKN 1A implied the possible control of cell cycle arrest at G1/S phase. This study is expected to extend our understanding on the pathogenesis of SARS at a molecular level

  4. Active sensor synergy for arctic cloud microphysics

    Directory of Open Access Journals (Sweden)

    Sato Kaori

    2018-01-01

    Full Text Available In this study, we focus on the retrieval of liquid and ice-phase cloud microphysics from spaceborne and ground-based lidar-cloud radar synergy. As an application of the cloud retrieval algorithm developed for the EarthCARE satellite mission (JAXA-ESA [1], the derived statistics of cloud microphysical properties in high latitudes and their relation to the Arctic climate are investigated.

  5. Postural Hand Synergies during Environmental Constraint Exploitation

    Directory of Open Access Journals (Sweden)

    Cosimo Della Santina

    2017-08-01

    Full Text Available Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings.

  6. Scientific Synergy between LSST and Euclid

    Science.gov (United States)

    Rhodes, Jason; Nichol, Robert C.; Aubourg, Éric; Bean, Rachel; Boutigny, Dominique; Bremer, Malcolm N.; Capak, Peter; Cardone, Vincenzo; Carry, Benoît; Conselice, Christopher J.; Connolly, Andrew J.; Cuillandre, Jean-Charles; Hatch, N. A.; Helou, George; Hemmati, Shoubaneh; Hildebrandt, Hendrik; Hložek, Renée; Jones, Lynne; Kahn, Steven; Kiessling, Alina; Kitching, Thomas; Lupton, Robert; Mandelbaum, Rachel; Markovic, Katarina; Marshall, Phil; Massey, Richard; Maughan, Ben J.; Melchior, Peter; Mellier, Yannick; Newman, Jeffrey A.; Robertson, Brant; Sauvage, Marc; Schrabback, Tim; Smith, Graham P.; Strauss, Michael A.; Taylor, Andy; Von Der Linden, Anja

    2017-12-01

    Euclid and the Large Synoptic Survey Telescope (LSST) are poised to dramatically change the astronomy landscape early in the next decade. The combination of high-cadence, deep, wide-field optical photometry from LSST with high-resolution, wide-field optical photometry, and near-infrared photometry and spectroscopy from Euclid will be powerful for addressing a wide range of astrophysical questions. We explore Euclid/LSST synergy, ignoring the political issues associated with data access to focus on the scientific, technical, and financial benefits of coordination. We focus primarily on dark energy cosmology, but also discuss galaxy evolution, transient objects, solar system science, and galaxy cluster studies. We concentrate on synergies that require coordination in cadence or survey overlap, or would benefit from pixel-level co-processing that is beyond the scope of what is currently planned, rather than scientific programs that could be accomplished only at the catalog level without coordination in data processing or survey strategies. We provide two quantitative examples of scientific synergies: the decrease in photo-z errors (benefiting many science cases) when high-resolution Euclid data are used for LSST photo-z determination, and the resulting increase in weak-lensing signal-to-noise ratio from smaller photo-z errors. We briefly discuss other areas of coordination, including high-performance computing resources and calibration data. Finally, we address concerns about the loss of independence and potential cross-checks between the two missions and the potential consequences of not collaborating.

  7. Predicting synergy in atomic layer etching

    Energy Technology Data Exchange (ETDEWEB)

    Kanarik, Keren J. [Lam Research Corp., Fremont, CA (United States); Tan, Samantha [Lam Research Corp., Fremont, CA (United States); Yang, Wenbing [Lam Research Corp., Fremont, CA (United States); Kim, Taeseung [Lam Research Corp., Fremont, CA (United States); Lill, Thorsten [Lam Research Corp., Fremont, CA (United States); Kabansky, Alexander [Lam Research Corp., Fremont, CA (United States); Hudson, Eric A. [Lam Research Corp., Fremont, CA (United States); Ohba, Tomihito [Lam Research Corp., Fremont, CA (United States); Nojiri, Kazuo [Lam Research Corp., Fremont, CA (United States); Yu, Jengyi [Lam Research Corp., Fremont, CA (United States); Wise, Rich [Lam Research Corp., Fremont, CA (United States); Berry, Ivan L. [Lam Research Corp., Fremont, CA (United States); Pan, Yang [Lam Research Corp., Fremont, CA (United States); Marks, Jeffrey [Lam Research Corp., Fremont, CA (United States); Gottscho, Richard A. [Lam Research Corp., Fremont, CA (United States)

    2017-03-27

    Atomic layer etching (ALE) is a multistep process used today in manufacturing for removing ultrathin layers of material. In this article, the authors report on ALE of Si, Ge, C, W, GaN, and SiO2 using a directional (anisotropic) plasma-enhanced approach. The authors analyze these systems by defining an “ALE synergy” parameter which quantifies the degree to which a process approaches the ideal ALE regime. This parameter is inspired by the ion-neutral synergy concept introduced in the 1979 paper by Coburn and Winters. ALE synergy is related to the energetics of underlying surface interactions and is understood in terms of energy criteria for the energy barriers involved in the reactions. Synergistic behavior is observed for all of the systems studied, with each exhibiting behavior unique to the reactant–material combination. By systematically studying atomic layer etching of a group of materials, the authors show that ALE synergy scales with the surface binding energy of the bulk material. This insight explains why some materials are more or less amenable to the directional ALE approach. Furthermore, they conclude that ALE is both simpler to understand than conventional plasma etch processing and is applicable to metals, semiconductors, and dielectrics.

  8. Genomic Analysis and Surveillance of the Coronavirus Dominant in Ducks in China.

    Directory of Open Access Journals (Sweden)

    Qing-Ye Zhuang

    Full Text Available The genetic diversity, evolution, distribution, and taxonomy of some coronaviruses dominant in birds other than chickens remain enigmatic. In this study we sequenced the genome of a newly identified coronavirus dominant in ducks (DdCoV, and performed a large-scale surveillance of coronaviruses in chickens and ducks using a conserved RT-PCR assay. The viral genome harbors a tandem repeat which is rare in vertebrate RNA viruses. The repeat is homologous to some proteins of various cellular organisms, but its origin remains unknown. Many substitutions, insertions, deletions, and some frameshifts and recombination events have occurred in the genome of the DdCoV, as compared with the coronavirus dominant in chickens (CdCoV. The distances between DdCoV and CdCoV are large enough to separate them into different species within the genus Gammacoronavirus. Our surveillance demonstrated that DdCoVs and CdCoVs belong to different lineages and occupy different ecological niches, further supporting that they should be classified into different species. Our surveillance also demonstrated that DdCoVs and CdCoVs are prevalent in live poultry markets in some regions of China. In conclusion, this study shed novel insight into the genetic diversity, evolution, distribution, and taxonomy of the coronaviruses circulating in chickens and ducks.

  9. Structure of the C-terminal domain of nsp4 from feline coronavirus

    International Nuclear Information System (INIS)

    Manolaridis, Ioannis; Wojdyla, Justyna A.; Panjikar, Santosh; Snijder, Eric J.; Gorbalenya, Alexander E.; Berglind, Hanna; Nordlund, Pär; Coutard, Bruno; Tucker, Paul A.

    2009-01-01

    The structure of the cytosolic C-terminal domain of nonstructural protein 4 from feline coronavirus has been determined and analyzed. Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4 3 . The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions

  10. Structure of the C-terminal domain of nsp4 from feline coronavirus

    Energy Technology Data Exchange (ETDEWEB)

    Manolaridis, Ioannis; Wojdyla, Justyna A.; Panjikar, Santosh [EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg (Germany); Snijder, Eric J.; Gorbalenya, Alexander E. [Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden (Netherlands); Berglind, Hanna; Nordlund, Pär [Division of Biophysics, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, Karolinska Institute, SE-171 77 Stockholm (Sweden); Coutard, Bruno [Laboratoire Architecture et Fonction des Macromolécules Biologiques, UMR 6098, AFMB-CNRS-ESIL, Case 925, 163 Avenue de Luminy, 13288 Marseille (France); Tucker, Paul A., E-mail: tucker@embl-hamburg.de [EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg (Germany)

    2009-08-01

    The structure of the cytosolic C-terminal domain of nonstructural protein 4 from feline coronavirus has been determined and analyzed. Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4{sub 3}. The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions.

  11. [Prevalence and clinical characteristics of coronavirus NL63 infection in children hospitalized for acute lower respiratory tract infections in Changsha].

    Science.gov (United States)

    Zhang, Fei; Zhang, Bing; Xie, Zhi-Ping; Gao, Han-Chun; Zhao, Xin; Zhong, Li-Li; Zhou, Qiong-Hua; Hou, Yun-De; Duan, Zhao-Jun

    2012-04-01

    The main objective of this study was to explore the prevalence and clinical characteristics of human coronavirus NL63 infection in hospitalized children with acute lower respiratory tract infection (ALRTI) in Changsha. Nasopharyngeal aspirates (NPA) samples were collected from 1185 hospitalized children with ALRTI at the People's Hospital of Hunan province, between September 2008 and October 2010. Reverse transcriptase polymerase chain reaction (RT-PCR) was employed to screen for coronavirus NL63, which is a 255 bp fragment of a part of N gene. All positive amplification products were confirmed by sequencing and compared with those in GenBank. The overall frequency of coronavirus NL63 infection was 0.8%, 6 (60%) out of the coronavirus NL63 positive patients were detected in summer, 2 in autumn, 1 in spring and winter, respectively. The patients were from 2 months to two and a half years old. The clinical diagnosis was bronchopneumonia (60%), bronchiolitis (30%), and acute laryngotracheal bronchitis (10%). Four of the 10 cases had critical illness, 4 cases had underlying diseases, and 7 cases had mixed infection with other viruses. The homogeneity of coronavirus NL63 with those published in the GenBank at nucleotide levels was 97%-100%. Coronavirus NL63 infection exists in hospitalized children with acute lower respiratory tract infection in Changsha. Coronavirus NL63 infections are common in children under 3 years of age. There is significant difference in the infection rate between the boys and the girls: the boys had higher rate than the girls. The peak of prevalence of the coronavirus NL63 was in summer. A single genetic lineage of coronavirus NL63 was revealed in human subjects in Changsha. Coronavirus NL63 may also be one of the lower respiratory pathogen in China.

  12. SARS and Population Health Technology

    OpenAIRE

    Eysenbach, Gunther

    2003-01-01

    The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smar...

  13. SARS-related perceptions in Hong Kong.

    Science.gov (United States)

    Lau, Joseph T F; Yang, Xilin; Pang, Ellie; Tsui, H Y; Wong, Eric; Wing, Yun Kwok

    2005-03-01

    To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and approximately equals 70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and approximately equals 40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.

  14. Coronaviruses in guano from Pteropus medius bats in Peradeniya, Sri Lanka.

    Science.gov (United States)

    Kudagammana, H D W S; Thevanesam, V; Chu, D K W; Eriyagama, N B; Peiris, J S M; Noordeen, F

    2018-03-02

    Bats are a unique group of mammals well suited to be hosts for emerging viruses. With current rates of deforestation and urbanization, redistribution of bat habitats to urban and suburban areas may bring bats into closer contact with livestock and humans. Common flying fox, Pteropus medius (previously known as Pteropus giganteus), forms large communal roosts on treetops, often in close proximity to human habitation in Sri Lanka. This report describes the detection of coronavirus RNA in P. medius bat guano collected in Peradeniya, Sri Lanka. These viruses had >97% nucleotide identity with coronaviruses detected in Cynopterus sphinx, Scotophilus heathii and S. kuhlii bats in Thailand. Pteropus medius is widespread in Asia and appears to excrete group D coronaviruses, which are hitherto confined to bats; however, these findings may have public health implications in the future. © 2018 Blackwell Verlag GmbH.

  15. Human Coronaviruses 229E and NL63: Close Yet Still So Far

    Directory of Open Access Journals (Sweden)

    Ronald Dijkman

    2009-04-01

    Full Text Available HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.

  16. Synergies of the Liberalization of the Railway Transport Market

    Directory of Open Access Journals (Sweden)

    Panák Michal

    2017-01-01

    Full Text Available The liberalization of transport market brings various effects, which in the context of the assessment of synergies can affect in different ways the company, a customer as such, and transport undertakings operating on the railway transport market as well. This paper provides an innovative perspective on the relationship between liberalization and synergy, defining new types of synergies that have not yet been monitored in the conditions of railway transport. This approach is interesting because of the possibility of assessing the operation of railway undertakings in the open transport market. The eminent is characteristic of integration type synergies and emergence type synergies in relation to railway transport, as well as the breakdown of synergies in relation to the customer and carrier.

  17. SARS-related Perceptions in Hong Kong

    OpenAIRE

    Lau, Joseph T.F.; Yang, Xilin; Pang, Ellie; Tsui, H.Y.; Wong, Eric; Wing, Yun Kwok

    2005-01-01

    To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means o...

  18. SAR system development for UAV multicopter platforms

    OpenAIRE

    Escartin Martínez, Antonio

    2015-01-01

    SAR system development for UAV multicopter platforms This thesis describes the optimization of a synthetic aperture radar (SAR) at X-band and its integration into an unmanned aerial vehicle (UAV) of type octocopter. For such optimization the SAR system functionality was extended from singlepol to fulpol and it has been optimized at hardware level in order to improve its quality against noise figure. After its integration into the octocopter platform, its features has been used in order to ...

  19. Proteomic analysis of purified coronavirus infectious bronchitis virus particles

    Directory of Open Access Journals (Sweden)

    Shu Dingming

    2010-06-01

    Full Text Available Abstract Background Infectious bronchitis virus (IBV is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. Results Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%, molecular chaperone (18%, macromolcular biosynthesis proteins (17%, cytoskeletal proteins (15%, signal transport proteins (15%, protein degradation (8%, chromosome associated proteins (2%, ribosomal proteins (2%, and other function proteins (3%. Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. Conclusions The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.

  20. Suppression of feline coronavirus replication in vitro by cyclosporin A

    Directory of Open Access Journals (Sweden)

    Tanaka Yoshikazu

    2012-04-01

    Full Text Available Abstract The feline infectious peritonitis virus (FIPV is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA, an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT to bind cellular cyclophilins (CyP, dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP but not CyP did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.

  1. Can Measured Synergy Excitations Accurately Construct Unmeasured Muscle Excitations?

    Science.gov (United States)

    Bianco, Nicholas A; Patten, Carolynn; Fregly, Benjamin J

    2018-01-01

    Accurate prediction of muscle and joint contact forces during human movement could improve treatment planning for disorders such as osteoarthritis, stroke, Parkinson's disease, and cerebral palsy. Recent studies suggest that muscle synergies, a low-dimensional representation of a large set of muscle electromyographic (EMG) signals (henceforth called "muscle excitations"), may reduce the redundancy of muscle excitation solutions predicted by optimization methods. This study explores the feasibility of using muscle synergy information extracted from eight muscle EMG signals (henceforth called "included" muscle excitations) to accurately construct muscle excitations from up to 16 additional EMG signals (henceforth called "excluded" muscle excitations). Using treadmill walking data collected at multiple speeds from two subjects (one healthy, one poststroke), we performed muscle synergy analysis on all possible subsets of eight included muscle excitations and evaluated how well the calculated time-varying synergy excitations could construct the remaining excluded muscle excitations (henceforth called "synergy extrapolation"). We found that some, but not all, eight-muscle subsets yielded synergy excitations that achieved >90% extrapolation variance accounted for (VAF). Using the top 10% of subsets, we developed muscle selection heuristics to identify included muscle combinations whose synergy excitations achieved high extrapolation accuracy. For 3, 4, and 5 synergies, these heuristics yielded extrapolation VAF values approximately 5% lower than corresponding reconstruction VAF values for each associated eight-muscle subset. These results suggest that synergy excitations obtained from experimentally measured muscle excitations can accurately construct unmeasured muscle excitations, which could help limit muscle excitations predicted by muscle force optimizations.

  2. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013.

    Science.gov (United States)

    Hemida, M G; Perera, R A; Wang, P; Alhammadi, M A; Siu, L Y; Li, M; Poon, L L; Saif, L; Alnaeem, A; Peiris, M

    2013-12-12

    In Saudi Arabia, including regions of Riyadh and Al Ahsa, pseudoparticle neutralisation (ppNT) and microneutralisation (MNT) tests detected no antibodies to Middle East Respiratory Syndrome coronavirus (MERS-CoV) in sheep (n= 100), goats (n= 45), cattle (n= 50) and chickens (n= 240). Dromedary camels however, had a high prevalence of MERS-CoV antibodies. Bovine coronavirus (BCoV) infected sera from cattle had no cross-reactivity in MERS-CoV ppNT or MNT, while many dromedary camels’ sera reacted to both BCoV and MERS-CoV. Some nevertheless displayed specific serologic reaction profiles to MERS-CoV.

  3. Genetic variation of the human α-2-Heremans-Schmid glycoprotein (AHSG gene associated with the risk of SARS-CoV infection.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zhu

    Full Text Available Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV. α-2-Heremans-Schmid Glycoprotein (AHSG, which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A is an ω-oxidase that inactivates Leukotriene B4 (LTB4 in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD maps of these two genes were built with Haploview using data on CHB+JPT (version 2 from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51; rs4917 (AOR 1.84; 95% CI 1.02-3.34; and rs3794987 (AOR 2.01; 95% CI 1.10-3.68. To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30-2.04 was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37-2.09. The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS

  4. Biomimetic microstructures for photonic and fluidic synergies

    Science.gov (United States)

    Vasileiou, Maria; Mpatzaka, Theodora; Alexandropoulos, Dimitris; Vainos, Nikolaos A.

    2017-08-01

    Nature-inspired micro- and nano-structures offer a unique platform for the development of novel synergetic systems combining photonic and microfluidic functionalities. In this context, we examine the paradigm of butterfly Vanessa cardui and develop artificial diffractive microstructures inspired by its natural designs. Softlithographic and nanoimprint protocols are developed to replicate surfaces of natural specimens. Further to their optical behavior, interphases tailored by such microstructures exhibit enhanced hydrophobic properties, as compared to their planar counterparts made of the same materials. Such synergies exploited by new design approaches pave the way to prospective optofluidic, lab-on-chip and sensing applications.

  5. Sentinel-3 SAR Altimetry Toolbox

    Science.gov (United States)

    Benveniste, Jerome; Lucas, Bruno; DInardo, Salvatore

    2015-04-01

    The prime objective of the SEOM (Scientific Exploitation of Operational Missions) element is to federate, support and expand the large international research community that the ERS, ENVISAT and the Envelope programmes have build up over the last 20 years for the future European operational Earth Observation missions, the Sentinels. Sentinel-3 builds directly on a proven heritage of ERS-2 and Envisat, and CryoSat-2, with a dual-frequency (Ku and C band) advanced Synthetic Aperture Radar Altimeter (SRAL) that provides measurements at a resolution of ~300m in SAR mode along track. Sentinel-3 will provide exact measurements of sea-surface height along with accurate topography measurements over sea ice, ice sheets, rivers and lakes. The first of the two Sentinels is expected to be launched in early 2015. The current universal altimetry toolbox is BRAT (Basic Radar Altimetry Toolbox) which can read all previous and current altimetry mission's data, but it does not have the capabilities to read the upcoming Sentinel-3 L1 and L2 products. ESA will endeavour to develop and supply this capability to support the users of the future Sentinel-3 SAR Altimetry Mission. BRAT is a collection of tools and tutorial documents designed to facilitate the processing of radar altimetry data. This project started in 2005 from the joint efforts of ESA (European Space Agency) and CNES (Centre National d'Etudes Spatiales), and it is freely available at http://earth.esa.int/brat. The tools enable users to interact with the most common altimetry data formats, the BratGUI is the front-end for the powerful command line tools that are part of the BRAT suite. BRAT can also be used in conjunction with Matlab/IDL (via reading routines) or in C/C++/Fortran via a programming API, allowing the user to obtain desired data, bypassing the data-formatting hassle. BRAT can be used simply to visualise data quickly, or to translate the data into other formats such as netCDF, ASCII text files, KML (Google Earth

  6. Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavius molecules

    International Nuclear Information System (INIS)

    Wu, H.-Y.; Guy, James S.; Yoo, Dongwan; Vlasak, Reinhard; Urbach, Ena; Brian, David A.

    2003-01-01

    5' and 3' UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5' UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5' UTR and adjacent 289-nt sequences, and 3' UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3' UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5' and 3' replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members

  7. Alberta industrial synergy CO2 programs initiative

    International Nuclear Information System (INIS)

    Yildirim, E.

    1998-01-01

    The various industrial sectors within Alberta produce about 350,000 tonnes of CO 2 per day. This presentation was concerned with how this large volume and high concentration of CO 2 can be used in industrial and agricultural applications, because every tonne of CO 2 used for such purposes is a tonne that does not end up in the atmosphere. There is a good potential for an industrial synergy between the producers and users of CO 2 . The Alberta Industrial Synergy CO 2 Programs Initiative was established to ultimately achieve a balance between the producers of CO 2 and the users of CO 2 by creating ways to use the massive quantities of CO 2 produced by Alberta's hydrocarbon-based economy. The Alberta CO 2 Research Steering Committee was created to initiate and support CO 2 programs such as: (1) CO 2 use in enhanced oil recovery, (2) creation of a CO 2 production inventory, (3) survey of CO 2 users and potential users, (4) investigation of process issues such as power generation, oil sands and cement manufacturing, and (5) biofixation by plants, (6) other disposal options (e.g. in depleted oil and gas reservoirs, in aquifers, in tailings ponds, in coal beds). The single most important challenge was identified as 'rationalizing the formation of the necessary infrastructure'. Failing to do that will greatly impede efforts directed towards CO 2 utilization

  8. Geometric calibration of ERS satellite SAR images

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    2001-01-01

    Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...

  9. PHARUS: A C-band Airborne SAR

    NARCIS (Netherlands)

    Hoogeboom, P.; Koomen, P.J.; Pouwels, H.; Snoeij, P.

    1990-01-01

    In The Netherlands a plan to design aircraft and build a polarimetric C-band SAR system of a novel design, called PHARUS (PHased Array Universal SAR) is carried out by three institutes. These institutes are the Physics and Electronics Laboratory TNO in The Hague (prime contractor and project

  10. Experimental inoculation of equine coronavirus into Japanese draft horses.

    Science.gov (United States)

    Nemoto, Manabu; Oue, Yasuhiro; Morita, Yoshinori; Kanno, Toru; Kinoshita, Yuta; Niwa, Hidekazu; Ueno, Takanori; Katayama, Yoshinari; Bannai, Hiroshi; Tsujimura, Koji; Yamanaka, Takashi; Kondo, Takashi

    2014-12-01

    Recently, outbreaks associated with equine coronavirus (ECoV) have occurred in Japan and the United States. While ECoV is likely to be pathogenic to horses, it has not been shown that experimental inoculation of horses with ECoV produces clinical signs of disease. In this study, we inoculated three Japanese draft horses with an ECoV-positive diarrheic fecal sample to confirm infection after inoculation and to investigate the clinical course and virus shedding patterns of ECoV. Virus neutralization tests showed that all three horses became infected with ECoV. Two of the three horses developed clinical signs similar to those observed during ECoV outbreaks, including fever, anorexia, and gastrointestinal dysfunction. All horses excreted a large amount of virus into their feces for more than 9 days after inoculation regardless of the presence or absence of clinical signs, which suggests that feces are an important source of ECoV infection. ECoV was also detected in nasal swabs from all horses, suggesting that respiratory transmission of ECoV may occur. Both symptomatic horses developed viremia, while the asymptomatic horse did not. White blood cell counts and serum amyloid A concentrations changed relative to the clinical condition of the inoculated horses; these may be useful markers for monitoring the clinical status of horses infected with ECoV. This is the first report of induction of clinical signs of ECoV infection in horses by experimental inoculation. These clinical and virological findings should aid further investigation of the pathogenesis of ECoV.

  11. Human coronavirus and severe acute respiratory infection in Southern Brazil.

    Science.gov (United States)

    Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

    2016-05-01

    Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

  12. Managing Risk and Synergies R&D-Collaborations

    DEFF Research Database (Denmark)

    Mahnke, Volker; Overby, Mikkel Lucas

    2004-01-01

    &D collaborations simultaneously. We use modern portfolio theory as an analogy to show how companies active in mobile telecommunication manage risks and create synergies by simultaneously engaging in several inter-firm collaborations.Keywords: Portfolio theory, risk, synergy, R&D collaboration, mobile commerce...

  13. Tapping Geography's Potential for Synergy with Creative Instructional Approaches

    Science.gov (United States)

    Conway-Gomez, Kristen; Williams, Nikki; Atkinson-Palombo, Carol; Ahlqvist, Ola; Kim, Eje; Morgan, Miranda

    2011-01-01

    We define synergy, explain its importance within the context of rapidly changing academia, and provide examples of how geographic educators have used creative instructional approaches to create synergies. Both the content of geography and some of the instructional approaches used by geographic educators support the discipline's ability to deliver…

  14. Does Synergy Exist in Nursing? A Concept Analysis.

    Science.gov (United States)

    Witges, Kim A; Scanlan, Judith M

    2015-01-01

    The aim is to analyze the concept of synergy, particularly as the concept applies to teamwork, and determine if the concept has utility in improving the work environment for nurses. Tackling nursing shortages that result from a poor work environment is a priority for many nurse leaders. Producing synergy among teams may be an effective strategy in enhancing the work environment. However, the understanding of synergy and the ability to produce synergy among teams has been seldom highlighted or discussed within nursing literature. Walker and Avant's approach was used to guide this concept analysis of synergy. Literature searches involved databases (PsycInfo, Medline, Cumulative Index for Nursing and Allied Health Literature [CINAHL], and Scopus), Internet search engines (Google), and hand searches. The analysis suggests that synergy is an outcome of the successful collaboration of the following three attributes: group cohesion, the pursuit of a common goal, and the achievement of a positive gain, considerably more than what was thought possible by the group. The foundation for this accomplishment requires an underlying feeling of special importance, the acknowledgment of each member's role, and open communication and dialogue among members. Nursing leaders would benefit from a broader understanding of synergy, and the mindful application and utility of synergy as an outcome of effective teamwork among nurses. © 2014 Wiley Periodicals, Inc.

  15. Synergy: a framework for leadership development and transformation.

    Science.gov (United States)

    Pacini, Christine M

    2005-06-01

    The Synergy Model has been adopted as an organizing framework for nursing practice, education, and leadership at Clarian Health Partners, Inc. of Indiana. This article describes the evolution of educational programs at Clarian, in concert with the implementation of the Synergy Model. Philosophical and operational changes in staff orientation, professional development, and management development are described.

  16. Muscle synergies evoked by microstimulation are preferentially encoded during behavior

    Directory of Open Access Journals (Sweden)

    Simon Alexander Overduin

    2014-03-01

    Full Text Available Electrical microstimulation studies provide some of the most direct evidence for the neural representation of muscle synergies. These synergies, i.e. coordinated activations of groups of muscles, have been proposed as building blocks for the construction of motor behaviors by the nervous system. Intraspinal or intracortical microstimulation has been shown to evoke muscle patterns that can be resolved into a small set of synergies similar to those seen in natural behavior. However, questions remain about the validity of microstimulation as a probe of neural function, particularly given the relatively long trains of supratheshold stimuli used in these studies. Here, we examined whether muscle synergies evoked during intracortical microstimulation in two rhesus macaques were similarly encoded by nearby motor cortical units during a purely voluntary behavior involving object reach, grasp, and carry movements. At each microstimulation site we identified the synergy most strongly evoked among those extracted from muscle patterns evoked over all microstimulation sites. For each cortical unit recorded at the same microstimulation site, we then identified the synergy most strongly encoded among those extracted from muscle patterns recorded during the voluntary behavior. We found that the synergy most strongly evoked at an intracortical microstimulation site matched the synergy most strongly encoded by proximal units more often than expected by chance. These results suggest a common neural substrate for microstimulation-evoked motor responses and for the generation of muscle patterns during natural behaviors.

  17. Deep learning for SAR image formation

    Science.gov (United States)

    Mason, Eric; Yonel, Bariscan; Yazici, Birsen

    2017-04-01

    The recent success of deep learning has lead to growing interest in applying these methods to signal processing problems. This paper explores the applications of deep learning to synthetic aperture radar (SAR) image formation. We review deep learning from a perspective relevant to SAR image formation. Our objective is to address SAR image formation in the presence of uncertainties in the SAR forward model. We present a recurrent auto-encoder network architecture based on the iterative shrinkage thresholding algorithm (ISTA) that incorporates SAR modeling. We then present an off-line training method using stochastic gradient descent and discuss the challenges and key steps of learning. Lastly, we show experimentally that our method can be used to form focused images in the presence of phase uncertainties. We demonstrate that the resulting algorithm has faster convergence and decreased reconstruction error than that of ISTA.

  18. Distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229E in bats, Ghana

    Czech Academy of Sciences Publication Activity Database

    Pfefferle, S.; Oppong, S.; Drexler, J. F.; Gloza-Rausch, F.; Ipsen, A.; Seebens, A.; Müller, M. A.; Annan, A.; Vallo, Peter; Adu-Sarkodie, Y.; Kruppa, T. F.; Drosten, C.

    2009-01-01

    Roč. 15, č. 9 (2009), s. 1377-1384 ISSN 1080-6040 Grant - others:German Ministry of Education and Research(XE) SSPE-CT-2005-022639; FP7(XE) INFRASTRUCTURES-2008-No 228292; Bundesamt für Bevölkerungsschutz und Katastrophenhilfe(DE) BBK-F-440-00-1 Institutional research plan: CEZ:AV0Z60930519 Keywords : SARS-like * phylogenetic analysis * RNA * gastroenteritis * prevalence * diversity Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 6.794, year: 2009

  19. A reverse genetics system for avian coronavirus infectious bronchitis virus based on targeted RNA recombination

    NARCIS (Netherlands)

    van Beurden, Steven J; Berends, Alinda J; Krämer-Kühl, Annika; Spekreijse, Dieuwertje; Chénard, Gilles; Philipp, Hans-Christian; Mundt, Egbert; Rottier, Peter J M; Verheije, M Hélène

    2017-01-01

    BACKGROUND: Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens that causes severe economic losses in the poultry industry worldwide. Major advances in the study of the molecular biology of IBV have resulted from the development of reverse genetics systems for

  20. MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983-1997

    NARCIS (Netherlands)

    Müller, Marcel A; Corman, Victor Max; Jores, Joerg; Meyer, Benjamin; Younan, Mario; Liljander, Anne; Bosch, Berend-Jan; Lattwein, Erik; Hilali, Mosaad; Musa, Bakri E; Bornstein, Set; Drosten, Christian

    2014-01-01

    To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)-seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main

  1. Human Infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013

    NARCIS (Netherlands)

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Watson, Simon J.; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend Jan|info:eu-repo/dai/nl/273306049; Beer, Martin; Müller, Marcel A.; Kellam, Paul; Drosten, Christian

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species

  2. Middle East respiratory syndrome coronavirus in dromedary camels: An outbreak investigation

    NARCIS (Netherlands)

    B.L. Haagmans (Bart); S.H.S. Al Dhahiry (Said); C.B.E.M. Reusken (Chantal); V.S. Raj (Stalin); M. Galiano (Monica); R.H. Myers (Richard); G-J. Godeke (Gert-Jan); M. Jonges (Marcel); E. Farag (Elmoubasher); A. Diab (Ayman); H. Ghobashy (Hazem); F. Alhajri (Farhoud); M. Al-Thani (Mohamed); S.A. Al-Marri (Salih); H.E. Al Romaihi (Hamad); A. Al Khal (Abdullatif); A. Bermingham (Alison); A.D.M.E. Osterhaus (Albert); M.M. AlHajri (Mohd); M.P.G. Koopmans D.V.M. (Marion)

    2014-01-01

    textabstractBackground: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar

  3. Antibodies against MERS coronavirus in dromedaries, United Arab Emirates, 2003 and 2013

    NARCIS (Netherlands)

    Meyer, Benjamin; Müller, Marcel A.; Corman, Victor M.; Reusken, Chantal B E M; Ritz, Daniel; Godeke, Gert Jan; Lattwein, Erik; Kallies, Stephan; Siemens, Artem; van Beek, Janko; Drexler, Jan F.; Muth, Doreen; Bosch, Berend Jan; Wernery, Ulrich; Koopmans, Marion P G; Wernery, Renate; Drosten, Christian

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary

  4. Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses

    NARCIS (Netherlands)

    Rabouw, Huib H; Langereis, Martijn A; Knaap, Robert C M; Dalebout, Tim J; Canton, Javier; Sola, Isabel; Enjuanes, Luis; Bredenbeek, Peter J; Kikkert, Marjolein; de Groot, Raoul J; van Kuppeveld, Frank J M

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I

  5. A Structural analysis of M protein in coronavirus assembly and morphology

    DEFF Research Database (Denmark)

    W. Neuman, Benjamin; Kiss, Gabriella; H. Kunding, Andreas

    2011-01-01

    The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy...... protein functions to promote virus assembly....

  6. Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus

    NARCIS (Netherlands)

    Kusters, J G; Jager, E J; Niesters, H G; van der Zeijst, B A

    1990-01-01

    Under laboratory conditions coronaviruses were shown to have a high frequency of recombination. In The Netherlands, vaccination against infectious bronchitis virus (IBV) is performed with vaccines that contain several life-attenuated virus strains. These highly effective vaccines may create ideal

  7. Evidence for an Ancestral Association of Human Coronavirus 229E with Bats

    NARCIS (Netherlands)

    Corman, Victor Max; Baldwin, Heather J.; Tateno, Adriana Fumie; Zerbinati, Rodrigo Melim; Annan, Augustina; Owusu, Michael; Nkrumah, Evans Ewald; Maganga, Gael Darren; Oppong, Samuel; Adu-Sarkodie, Yaw; Vallo, Peter; da Silva Filho, Luiz Vicente Ribeiro Ferreira; Leroy, Eric M.; Thiel, Volker; van der Hoek, Lia; Poon, Leo L. M.; Tschapka, Marco; Drosten, Christian; Drexler, Jan Felix

    2015-01-01

    We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related

  8. Seroprevalence and risk factors for infection with equine coronavirus in healthy horses in the USA

    NARCIS (Netherlands)

    Kooijman, L.J.; James, K.; Mapes, S.M.; Theelen, M.J.P.; Pusterla, N.

    2017-01-01

    Equine coronavirus (ECoV) is considered an enteric pathogen of foals and has only recently been associated with infections in adult horses. Seroprevalence data is needed to better understand the epidemiology of ECoV in adult horses, evaluate diagnostic modalities and develop preventive measures. The

  9. Clinical, hematological, and biochemical findings in puppies with coronavirus and parvovirus enteritis

    Science.gov (United States)

    Castro, Tatiana X.; Cubel Garcia, Rita de Cássia N.; Gonçalves, Luciana P. S.; Costa, Erika M.; Marcello, Gracy C.G.; Labarthe, Norma V.; Mendes-de-Almeida, Flavya

    2013-01-01

    The clinical and laboratory findings in puppies naturally infected with canine coronavirus (CCoV) and/or canine parvovirus (CPV) were compared with findings in uninfected puppies. Lymphopenia was the only parameter related to CCoV infection that was statistically significant; vomiting, anorexia, lethargy, hemorrhagic fluid diarrhea, leukopenia, lymphopenia, thrombocytopenia, hypoglycemia, and hypoproteinemia were correlated with CPV infection. PMID:24155496

  10. Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

    KAUST Repository

    Kandeel, Mahmoud; Al-Taher, Abdulla; Li, Huifang; Schwingenschlö gl, Udo; Alnazawi, Mohamed

    2018-01-01

    Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs

  11. Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus

    NARCIS (Netherlands)

    Ulasli, M.; Verheije, M.H.; de Haan, C.A.M.; Reggiori, F.M.

    2011-01-01

    Coronaviruses (CoV) are enveloped positive-strand RNA viruses that induce different membrane rearrangements in infected cells in order to efficiently replicate and assemble. The origin, the protein composition and the function of these structures are not well established. To shed further light on

  12. Middle East Respiratory Syndrome Coronavirus Antibodies in Dromedary Camels, Bangladesh, 2015

    Science.gov (United States)

    Islam, Ariful; Rostal, Melinda K.; Islam, Shariful; Rahman, Mohammed Ziaur; Hossain, Mohammed Enayet; Uzzaman, Mohammed Salim; Munster, Vincent J.; Peiris, Malik; Flora, Meerjady Sabrina; Rahman, Mahmudur; Daszak, Peter

    2018-01-01

    Dromedary camels are bred domestically and imported into Bangladesh. In 2015, of 55 camels tested for Middle East respiratory syndrome coronavirus in Dhaka, 17 (31%) were seropositive, including 1 bred locally. None were PCR positive. The potential for infected camels in urban markets could have public health implications and warrants further investigation. PMID:29664373

  13. The first complete genome sequences of clinical isolates of human coronavirus 229E

    NARCIS (Netherlands)

    Farsani, Seyed Mohammad Jazaeri; Dijkman, Ronald; Jebbink, Maarten F.; Goossens, Herman; Ieven, Margareta; Deijs, Martin; Molenkamp, Richard; van der Hoek, Lia

    2012-01-01

    Human coronavirus 229E has been identified in the mid-1960s, yet still only one full-genome sequence is available. This full-length sequence has been determined from the cDNA-clone Inf-1 that is based on the lab-adapted strain VR-740. Lab-adaptation might have resulted in genomic changes, due to

  14. SARS: systematic review of treatment effects.

    Directory of Open Access Journals (Sweden)

    Lauren J Stockman

    2006-09-01

    Full Text Available 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

  15. Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction

    Directory of Open Access Journals (Sweden)

    Huang Jun

    2012-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction. Results We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A, lysine (K or aspartic acid (D, respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously. Conclusions We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.

  16. Pains and Gains from China’s Experiences with Emerging Epidemics: From SARS to H7N9

    Directory of Open Access Journals (Sweden)

    Pengfei Wei

    2016-01-01

    Full Text Available Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS- coronavirus (Cov, H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China’s infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1 enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2 prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3 increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.

  17. SARS and population health technology.

    Science.gov (United States)

    Eysenbach, Gunther

    2003-01-01

    The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smart homes. In the context of an outbreak or bioterrorism attack, such technologies may help to gather intelligence and detect diseases early, and communicate and exchange information electronically worldwide. Some of the technologies brought forward during the SARS epidemic may have been primarily motivated by marketing efforts, or were more directed towards reassuring people that "something is being done," ie, fighting an "epidemic of fear." To understand "fear epidemiology" is important because early warning systems monitoring data from a large number of people may not be able to discriminate between a biological epidemic and an epidemic of fear. The need for critical evaluation of all of these technologies is stressed.

  18. Muscle synergy analysis in children with cerebral palsy

    Science.gov (United States)

    Tang, Lu; Li, Fei; Cao, Shuai; Zhang, Xu; Wu, De; Chen, Xiang

    2015-08-01

    Objective. To explore the mechanism of lower extremity dysfunction of cerebral palsy (CP) children through muscle synergy analysis. Approach. Twelve CP children were involved in this study, ten adults (AD) and eight typically developed (TD) children were recruited as a control group. Surface electromyographic (sEMG) signals were collected bilaterally from eight lower limb muscles of the subjects during forward walking at a comfortable speed. A nonnegative matrix factorization algorithm was used to extract muscle synergies. In view of muscle synergy differences in number, structure and symmetry, a model named synergy comprehensive assessment (SCA) was proposed to quantify the abnormality of muscle synergies. Main results. There existed larger variations between the muscle synergies of the CP group and the AD group in contrast with the TD group. Fewer mature synergies were recruited in the CP group, and many abnormal synergies specific to the CP group appeared. Specifically, CP children were found to recruit muscle synergies with a larger difference in structure and symmetry between two legs of one subject and different subjects. The proposed SCA scale demonstrated its great potential to quantitatively assess the lower-limb motor dysfunction of CP children. SCA scores of the CP group (57.00 ± 16.78) were found to be significantly less (p < 0.01) than that of the control group (AD group: 95.74 ± 2.04; TD group: 84.19 ± 11.76). Significance. The innovative quantitative results of this study can help us to better understand muscle synergy abnormality in CP children, which is related to their motor dysfunction and even the physiological change in their nervous system.

  19. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

    International Nuclear Information System (INIS)

    He Yuxian; Zhou Yusen; Liu Shuwen; Kou Zhihua; Li Wenhui; Farzan, Michael; Jiang Shibo

    2004-01-01

    The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, respectively. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS

  20. The Philosophy of Modern Scientific Knowledge: the Language of Synergy and the Synergy of Language

    Directory of Open Access Journals (Sweden)

    Larisa Kiyashchenko

    2011-04-01

    Full Text Available The issue of the formation of present-day scientific knowledge is viewed in the paper through the prism of language. Language is seen here not merely as an external form vis-a-vis the content of scientific knowledge, but rather as the mode of emergence and existence of scientific knowledge as a certain reality (Shverev 2001: 509,  the one that evolves as a result of cognitive and communicative practices in transdisciplinary studies. The mutual influence of the language of synergy and the synergy of language leads to a new unity of scientific experience and gives rise to the philosophy of transdisciplinarity (Киященко 2006: 17. 

  1. Pedagogical Synergy: Linking Assessment, Curriculum, and Instruction

    Directory of Open Access Journals (Sweden)

    Caro Rolheiser

    2010-05-01

    Full Text Available This paper describes the evolution of attempts to build coherence and capacity in an Ontario school district, focusing on the development of literacy strategies in all of the district’s elementary and secondary schools. In reviewing case studies in four elementary schools, the authors have identified three key elements (instruction, curriculum, and assessment as the key dimensions which have the greatest influence on student achievement. The authors of this paper present a new construct, pedagogical synergy, in which those three elements are combined. Improvements can occur at both the district and school levels when there are horizontal and reciprocal strategies for building capacity and increasing coherence. It is the mutual support between district and schools that provides the power in this new concept.

  2. Implementation synergies that exploit situational knowledge strategically

    DEFF Research Database (Denmark)

    Quitzau, Maj-Britt; Petersen, Jens-Phillip

    This paper illustrates how strategic and situated forms of knowledge may increase capacity to implement energy strategies in local urban development projects. Through analysis of front runner implementation projects, we show that the involved planners utilize situational learning processes...... strategically to develop more viable implementation trajectories. These findings resonate well with relational and network orienteered research in contemporary planning theory. In the selected case studies, we can see that planners deliberately seek to extend traditional planning approaches, like e.......g. regulation, with broader context‐specific learning processes. In doing so, we argue that – what we call – an implementation synergy is established by interlacing different forms of situational knowledge with strategic knowledge about how to reach a desired energy target. In conclusion, the paper identifies...

  3. SAR and LIDAR fusion: experiments and applications

    Science.gov (United States)

    Edwards, Matthew C.; Zaugg, Evan C.; Bradley, Joshua P.; Bowden, Ryan D.

    2013-05-01

    In recent years ARTEMIS, Inc. has developed a series of compact, versatile Synthetic Aperture Radar (SAR) systems which have been operated on a variety of small manned and unmanned aircraft. The multi-frequency-band SlimSAR has demonstrated a variety of capabilities including maritime and littoral target detection, ground moving target indication, polarimetry, interferometry, change detection, and foliage penetration. ARTEMIS also continues to build upon the radar's capabilities through fusion with other sensors, such as electro-optical and infrared camera gimbals and light detection and ranging (LIDAR) devices. In this paper we focus on experiments and applications employing SAR and LIDAR fusion. LIDAR is similar to radar in that it transmits a signal which, after being reflected or scattered by a target area, is recorded by the sensor. The differences are that a LIDAR uses a laser as a transmitter and optical sensors as a receiver, and the wavelengths used exhibit a very different scattering phenomenology than the microwaves used in radar, making SAR and LIDAR good complementary technologies. LIDAR is used in many applications including agriculture, archeology, geo-science, and surveying. Some typical data products include digital elevation maps of a target area and features and shapes extracted from the data. A set of experiments conducted to demonstrate the fusion of SAR and LIDAR data include a LIDAR DEM used in accurately processing the SAR data of a high relief area (mountainous, urban). Also, feature extraction is used in improving geolocation accuracy of the SAR and LIDAR data.

  4. First full length sequences of the S gene of European isolates reveal further diversity among turkey coronaviruses.

    OpenAIRE

    2011-01-01

    Abstract An increasing incidence of enteric disorders clinically evocative of the poult enteritis complex has been observed in turkeys in France since 2003. Using a newly designed real-time RT-PCR assay specific for the nucleocapsid (N) gene of infectious bronchitis virus (IBV) and turkey coronaviruses (TCoV), coronaviruses were identified in 37 % of the intestinal samples collected from diseased turkey flocks. The full length Spike (S) gene of these viruses was amplified, cloned a...

  5. Coronavirus gene 7 counteracts host defenses and modulates virus virulence.

    Directory of Open Access Journals (Sweden)

    Jazmina L G Cruz

    2011-06-01

    Full Text Available Transmissible gastroenteritis virus (TGEV genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7. Both the mutant and the parental (rTGEV-wt viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c, a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the

  6. Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

    Science.gov (United States)

    Chang, Chung-ke; Chen, Chia-Min Michael; Chiang, Ming-hui; Hsu, Yen-lan; Huang, Tai-huang

    2013-01-01

    The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

  7. Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

    Directory of Open Access Journals (Sweden)

    Chung-ke Chang

    Full Text Available The nucleocapsid (N phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD. A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

  8. On the synergy of SMAP, AMSR2 AND SENTINEL-1 for retrieving soil moisture

    Science.gov (United States)

    Santi, E.; Paloscia, S.; Pettinato, S.; Brocca, L.; Ciabatta, L.; Entekhabi, D.

    2018-03-01

    An algorithm for retrieving soil moisture content (SMC) from synergic use of both active and passive microwave acquisitions is presented. The algorithm takes advantage of the integration of microwave data from SMAP, Sentinel-1 and AMSR2 for overcoming the SMAP radar failure and obtaining a SMC product at enhanced resolution (0.1° × 0.1°) and improved accuracy with respect to the original SMAP radiometric SMC product. A disaggregation technique based on the Smoothing filter based intensity modulation (SFIM) allows combining the radiometric and SAR data. Disaggregated microwave data are used as inputs of an Artificial Neural Networks (ANN) based algorithm, which is able to exploit the synergy between active and passive acquisitions. The algorithm is defined, trained and tested using the SMEX02 experimental dataset and data simulated by forward electromagnetic models based on the Radiative Transfer Theory. Then the algorithm is adapted to satellite data and tested using one year of SMAP, AMSR2 and Sentinel-1 co-located data on a flat agricultural area located in the Po Valley, in northern Italy. Spatially distributed SMC values at 0.1° × 0.1° resolution generated by the Soil Water Balance Model (SWBM) are considered as reference for this purpose. The synergy of SMAP, Sentinel-1 and AMSR2 allowed increasing the correlation between estimated and reference SMC from R ≅ 0.68 of the SMAP based retrieval up to R ≅ 0.86 of the combination SMAP + Sentinel-1 + AMSR2. The corresponding Root Mean Square Error (RMSE) decreased from RMSE ≅ 0.04 m3/m3 to RMSE ≅ 0.024 m3/m3.

  9. Anticipatory synergy adjustments reflect individual performance of feedforward force control.

    Science.gov (United States)

    Togo, Shunta; Imamizu, Hiroshi

    2016-10-06

    We grasp and dexterously manipulate an object through multi-digit synergy. In the framework of the uncontrolled manifold (UCM) hypothesis, multi-digit synergy is defined as the coordinated control mechanism of fingers to stabilize variable important for task success, e.g., total force. Previous studies reported anticipatory synergy adjustments (ASAs) that correspond to a drop of the synergy index before a quick change of the total force. The present study compared ASA's properties with individual performances of feedforward force control to investigate a relationship of those. Subjects performed a total finger force production task that consisted of a phase in which subjects tracked target line with visual information and a phase in which subjects produced total force pulse without visual information. We quantified their multi-digit synergy through UCM analysis and observed significant ASAs before producing total force pulse. The time of the ASA initiation and the magnitude of the drop of the synergy index were significantly correlated with the error of force pulse, but not with the tracking error. Almost all subjects showed a significant increase of the variance that affected the total force. Our study directly showed that ASA reflects the individual performance of feedforward force control independently of target-tracking performance and suggests that the multi-digit synergy was weakened to adjust the multi-digit movements based on a prediction error so as to reduce the future error. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Synergy as a rationale for phage therapy using phage cocktails.

    Science.gov (United States)

    Schmerer, Matthew; Molineux, Ian J; Bull, James J

    2014-01-01

    Where phages are used to treat bacterial contaminations and infections, multiple phages are typically applied at once as a cocktail. When two or more phages in the cocktail attack the same bacterium, the combination may produce better killing than any single phage (synergy) or the combination may be worse than the best single phage (interference). Synergy is of obvious utility, especially if it can be predicted a priori, but it remains poorly documented with few examples known. This study addresses synergy in which one phage improves adsorption by a second phage. It first presents evidence of synergy from an experimental system of two phages and a mucoid E. coli host. The synergy likely stems from a tailspike enzyme produced by one of the phages. We then offer mathematical models and simulations to understand the dynamics of synergy and the enhanced magnitude of bacterial control possible. The models and observations complement each other and suggest that synergy may be of widespread utility and may be predictable from easily observed phenotypes.

  11. How valid are claims for synergy in published clinical studies?

    Science.gov (United States)

    Ocana, A; Amir, E; Yeung, C; Seruga, B; Tannock, I F

    2012-08-01

    Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies. We searched PubMed using the terms 'synergy' or 'synergistic' and 'cancer' to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial. Eighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P=0.25, chi-squared test). Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.

  12. Muscle synergies during bench press are reliable across days.

    Science.gov (United States)

    Kristiansen, Mathias; Samani, Afshin; Madeleine, Pascal; Hansen, Ernst Albin

    2016-10-01

    Muscle synergies have been investigated during different types of human movement using nonnegative matrix factorization. However, there are not any reports available on the reliability of the method. To evaluate between-day reliability, 21 subjects performed bench press, in two test sessions separated by approximately 7days. The movement consisted of 3 sets of 8 repetitions at 60% of the three repetition maximum in bench press. Muscle synergies were extracted from electromyography data of 13 muscles, using nonnegative matrix factorization. To evaluate between-day reliability, we performed a cross-correlation analysis and a cross-validation analysis, in which the synergy components extracted in the first test session were recomputed, using the fixed synergy components from the second test session. Two muscle synergies accounted for >90% of the total variance, and reflected the concentric and eccentric phase, respectively. The cross-correlation values were strong to very strong (r-values between 0.58 and 0.89), while the cross-validation values ranged from substantial to almost perfect (ICC3, 1 values between 0.70 and 0.95). The present findings revealed that the same general structure of the muscle synergies was present across days and the extraction of muscle synergies is thus deemed reliable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Wave directional spectrum from SAR imagery

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

    < 2m and the zero-crossing period during the satellite overpass is small (< 6s, �O�O < 60m). We therefore utilized the visit of one of the authors (Sarma) to the Southampton Oceanographic Centre, U.K., to procure two ERS-1 digital image mode SAR...-dimensional FFT as well as a computer program for downloading SAR data from CCT. Finally we owe a debt of gratitude to J C da Silva, Southampton Oceanographic Centre, U K for sharing some of his SAR data with us. References Allan T. D. (Ed) (1983...

  14. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  15. The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

    Science.gov (United States)

    Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

    2017-07-25

    Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

  16. Identifying SARS-CoV membrane protein amino acid residues linked to virus-like particle assembly.

    Directory of Open Access Journals (Sweden)

    Ying-Tzu Tseng

    Full Text Available Severe acute respiratory syndrome coronavirus (SARS-CoV membrane (M proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs when coexpressed with SARS-CoV nucleocapsid (N protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219 is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.

  17. AUTOMATIC INTERPRETATION OF HIGH RESOLUTION SAR IMAGES: FIRST RESULTS OF SAR IMAGE SIMULATION FOR SINGLE BUILDINGS

    Directory of Open Access Journals (Sweden)

    J. Tao

    2012-09-01

    Full Text Available Due to the all-weather data acquisition capabilities, high resolution space borne Synthetic Aperture Radar (SAR plays an important role in remote sensing applications like change detection. However, because of the complex geometric mapping of buildings in urban areas, SAR images are often hard to interpret. SAR simulation techniques ease the visual interpretation of SAR images, while fully automatic interpretation is still a challenge. This paper presents a method for supporting the interpretation of high resolution SAR images with simulated radar images using a LiDAR digital surface model (DSM. Line features are extracted from the simulated and real SAR images and used for matching. A single building model is generated from the DSM and used for building recognition in the SAR image. An application for the concept is presented for the city centre of Munich where the comparison of the simulation to the TerraSAR-X data shows a good similarity. Based on the result of simulation and matching, special features (e.g. like double bounce lines, shadow areas etc. can be automatically indicated in SAR image.

  18. Combined DEM Extration Method from StereoSAR and InSAR

    Science.gov (United States)

    Zhao, Z.; Zhang, J. X.; Duan, M. Y.; Huang, G. M.; Yang, S. C.

    2015-06-01

    A pair of SAR images acquired from different positions can be used to generate digital elevation model (DEM). Two techniques exploiting this characteristic have been introduced: stereo SAR and interferometric SAR. They permit to recover the third dimension (topography) and, at the same time, to identify the absolute position (geolocation) of pixels included in the imaged area, thus allowing the generation of DEMs. In this paper, StereoSAR and InSAR combined adjustment model are constructed, and unify DEM extraction from InSAR and StereoSAR into the same coordinate system, and then improve three dimensional positioning accuracy of the target. We assume that there are four images 1, 2, 3 and 4. One pair of SAR images 1,2 meet the required conditions for InSAR technology, while the other pair of SAR images 3,4 can form stereo image pairs. The phase model is based on InSAR rigorous imaging geometric model. The master image 1 and the slave image 2 will be used in InSAR processing, but the slave image 2 is only used in the course of establishment, and the pixels of the slave image 2 are relevant to the corresponding pixels of the master image 1 through image coregistration coefficient, and it calculates the corresponding phase. It doesn't require the slave image in the construction of the phase model. In Range-Doppler (RD) model, the range equation and Doppler equation are a function of target geolocation, while in the phase equation, the phase is also a function of target geolocation. We exploit combined adjustment model to deviation of target geolocation, thus the problem of target solution is changed to solve three unkonwns through seven equations. The model was tested for DEM extraction under spaceborne InSAR and StereoSAR data and compared with InSAR and StereoSAR methods respectively. The results showed that the model delivered a better performance on experimental imagery and can be used for DEM extraction applications.

  19. Monitoring informal settlements using SAR polarimetry

    CSIR Research Space (South Africa)

    Kleynhans, W

    2012-10-01

    Full Text Available for settlement mapping and detection has remained largely unexplored in Southern Africa. The objective of this study is to investigate the possible role that SAR polarimetry could play in the monitoring of informal settlements....

  20. Work session on the SAR. Pt. 2

    International Nuclear Information System (INIS)

    Burkart, K.

    1980-01-01

    The present paper contains the tables of the contribution of K. Burkart 'Work Session on the SAR' to the IAEA Interregional Training Course held in Sept/Oct. 1980 at the Kernforschungszentrum Karlsruhe. (RW)

  1. Image based SAR product simulation for analysis

    Science.gov (United States)

    Domik, G.; Leberl, F.

    1987-01-01

    SAR product simulation serves to predict SAR image gray values for various flight paths. Input typically consists of a digital elevation model and backscatter curves. A new method is described of product simulation that employs also a real SAR input image for image simulation. This can be denoted as 'image-based simulation'. Different methods to perform this SAR prediction are presented and advantages and disadvantages discussed. Ascending and descending orbit images from NASA's SIR-B experiment were used for verification of the concept: input images from ascending orbits were converted into images from a descending orbit; the results are compared to the available real imagery to verify that the prediction technique produces meaningful image data.

  2. Attribute Learning for SAR Image Classification

    Directory of Open Access Journals (Sweden)

    Chu He

    2017-04-01

    Full Text Available This paper presents a classification approach based on attribute learning for high spatial resolution Synthetic Aperture Radar (SAR images. To explore the representative and discriminative attributes of SAR images, first, an iterative unsupervised algorithm is designed to cluster in the low-level feature space, where the maximum edge response and the ratio of mean-to-variance are included; a cross-validation step is applied to prevent overfitting. Second, the most discriminative clustering centers are sorted out to construct an attribute dictionary. By resorting to the attribute dictionary, a representation vector describing certain categories in the SAR image can be generated, which in turn is used to perform the classifying task. The experiments conducted on TerraSAR-X images indicate that those learned attributes have strong visual semantics, which are characterized by bright and dark spots, stripes, or their combinations. The classification method based on these learned attributes achieves better results.

  3. SARS Patients and Their Close Contacts

    Science.gov (United States)

    ... Outreach Workers VIII. Infection Control for Laboratory and Pathology Procedures IX. Occupational Health Issues Appendix I1 Appendix ... SARS was recognized as a global threat in March 2003, after first appearing in Southern China in ...

  4. Multiple Input - Multiple Output (MIMO) SAR

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  5. Association of RANTES with the replication of severe acute respiratory syndrome coronavirus in THP-1 cells.

    Science.gov (United States)

    Li, D; Wu, N; Yao, H; Bader, A; Brockmeyer, Norbert H; Altmeyer, P

    2005-03-29

    Severe acute respiratory syndrome (SARS) is a novel infectious disease which is characterized by an overaggressive immune response. Chemokines are important inflammatory mediators and regulate disease due to viral infection. In previous study, we found that SARS-CoV has the ability to replicate in mononuclear cells. In present work, we sought to characterize the replication of SARS-CoV at the presence of RANTES in THP-1 cells. To determine whether RANTES play an role in the process of SARS, THP-1 cells were incubated with heat-inactivated SARS-CoV and ELISA was used to test RANTES levels in the supernatants; Then the effect of dexamethasone on the induced secretion was evaluated. Real-time PCR was used to investigate the effort of RANTES on the replication of SARS-CoV in vitro. Macrophages, induced by THP-1 cells, were used as cell model. Inactive SARS-CoV could induce THP-1 cells secret RANTES and this increase effect could not be suppressed by DXM. RANTES itself could inhibit the replication of SARS-CoV in THP-1 cells when it was added into the culture before or at the same time with the virus; No inhibition effect was shown when RANTES were added into the culture after SARS-CoV infected the cells.

  6. SAR Ambiguity Study for the Cassini Radar

    Science.gov (United States)

    Hensley, Scott; Im, Eastwood; Johnson, William T. K.

    1993-01-01

    The Cassini Radar's synthetic aperture radar (SAR) ambiguity analysis is unique with respect to other spaceborne SAR ambiguity analyses owing to the non-orbiting spacecraft trajectory, asymmetric antenna pattern, and burst mode of data collection. By properly varying the pointing, burst mode timing, and radar parameters along the trajectory this study shows that the signal-to-ambiguity ratio of better than 15 dB can be achieved for all images obtained by the Cassini Radar.

  7. Estimating Elevation Angles From SAR Crosstalk

    Science.gov (United States)

    Freeman, Anthony

    1994-01-01

    Scheme for processing polarimetric synthetic-aperture-radar (SAR) image data yields estimates of elevation angles along radar beam to target resolution cells. By use of estimated elevation angles, measured distances along radar beam to targets (slant ranges), and measured altitude of aircraft carrying SAR equipment, one can estimate height of target terrain in each resolution cell. Monopulselike scheme yields low-resolution topographical data.

  8. Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin.

    Science.gov (United States)

    Barnard, Dale L; Day, Craig W; Bailey, Kevin; Heiner, Matthew; Montgomery, Robert; Lauridsen, Larry; Winslow, Scott; Hoopes, Justin; Li, Joseph K-K; Lee, Jongdae; Carson, Dennis A; Cottam, Howard B; Sidwell, Robert W

    2006-08-01

    Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a replication model for severe acute respiratory syndrome (SARS) infections (Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K., Packard, M., Shieh, W.J., Zaki, S., Murphy, B., 2004. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in the respiratory tract of mice. J. Virol. 78, 3572-3577). Ribavirin given at 75 mg/kg 4 h prior to virus exposure and then given twice daily for 3 days beginning at day 0 was found to increase virus lung titers and extend the length of time that virus could be detected in the lungs of mice. Other IMP dehydrogenase inhibitors administered near maximum tolerated doses using the same dosing regimen as for ribavirin were found to slightly enhance virus replication in the lungs. In addition, ribavirin treatment seemed also to promote the production of pro-inflammatory cytokines 4 days after cessation of treatment, although after 3 days of treatment ribavirin inhibited pro-inflammatory cytokine production in infected mice, significantly reducing the levels of the cytokines IL-1alpha, interleukin-5 (IL-5), monocyte chemotactic protein-1 (MCP-1), and granulocyte-macrophage colony stimulating factor (GM-CSF). These findings suggest that ribavirin may actually contribute to the pathogenesis of SARS-CoV by prolonging and/or enhancing viral replication in the lungs. By not inhibiting viral replication in the lungs of infected mice, ribavirin treatment may have provided a continual source of stimulation for the inflammatory response

  9. Exploiting Laboratory and Heliophysics Plasma Synergies

    Directory of Open Access Journals (Sweden)

    Jill Dahlburg

    2010-05-01

    Full Text Available Recent advances in space-based heliospheric observations, laboratory experimentation, and plasma simulation codes are creating an exciting new cross-disciplinary opportunity for understanding fast energy release and transport mechanisms in heliophysics and laboratory plasma dynamics, which had not been previously accessible. This article provides an overview of some new observational, experimental, and computational assets, and discusses current and near-term activities towards exploitation of synergies involving those assets. This overview does not claim to be comprehensive, but instead covers mainly activities closely associated with the authors’ interests and reearch. Heliospheric observations reviewed include the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI on the National Aeronautics and Space Administration (NASA Solar Terrestrial Relations Observatory (STEREO mission, the first instrument to provide remote sensing imagery observations with spatial continuity extending from the Sun to the Earth, and the Extreme-ultraviolet Imaging Spectrometer (EIS on the Japanese Hinode spacecraft that is measuring spectroscopically physical parameters of the solar atmosphere towards obtaining plasma temperatures, densities, and mass motions. The Solar Dynamics Observatory (SDO and the upcoming Solar Orbiter with the Heliospheric Imager (SoloHI on-board will also be discussed. Laboratory plasma experiments surveyed include the line-tied magnetic reconnection experiments at University of Wisconsin (relevant to coronal heating magnetic flux tube observations and simulations, and a dynamo facility under construction there; the Space Plasma Simulation Chamber at the Naval Research Laboratory that currently produces plasmas scalable to ionospheric and magnetospheric conditions and in the future also will be suited to study the physics of the solar corona; the Versatile Toroidal Facility at the Massachusetts Institute of Technology that

  10. SARS: Key factors in crisis management.

    Science.gov (United States)

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  11. Food synergies for improving bioavailability of micronutrients from plant foods.

    Science.gov (United States)

    Nair, K Madhavan; Augustine, Little Flower

    2018-01-01

    Plant foods are endowed with micronutrients but an understanding of bioavailability is essential in countries primarily dependent on plant based foods. Bioavailability depends majorly on food synergies. This review examines the nature of certain food synergies and methods to screen and establish it as a strategy to control micronutrient deficiency in the populations. Strong evidence on the synergistic effect of inclusion of vitamin C rich fruits and non-vegetarian foods in enhancing the bioavailability of iron has been demonstrated. Fat is found to be synergistic for vitamin A absorption. Red wine and protein have been explored for zinc absorption and effect of fat has been studied for vitamin D. Methods for screening of bioavailability, and biomarkers to demonstrate the synergistic effects of foods are required. Translation of food synergy as a strategy requires adaptation to the context and popularization of intelligent food synergies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Target Choice and Unique Synergies in Global Mobile Telephony

    DEFF Research Database (Denmark)

    Claussen, Jörg; Köhler, Rebecca; Kretschmer, Tobias

    2018-01-01

    their foresight to select specific targets: First, they lower integration costs by selecting geographically close targets. This effect is stronger when buyer and target are in the same country, but only if the market is not so concentrated that it provokes regulatory interventions. Second, they select targets......The success of acquisitions rests on detecting and realizing unique synergies between buyer and target through their dyadic relationships. We study the role of unique dyad-specific synergies in the selection of takeover targets in the global mobile telecommunications industry. Firms use...... that can be acquired at a modest bid premium because they have asymmetric bargaining power. Finally, they select targets which can generate significant synergies due to technological synergies. Our work expands the existing target selection literature by studying dyad-specific factors within a single...

  13. Field Synergy Principle for Energy Conservation Analysis and Application

    Directory of Open Access Journals (Sweden)

    Qun Chen

    2010-01-01

    Full Text Available Optimization of mass and energy transfer process is critical to improve energy efficiency. In this contribution we introduce the field synergy principle as a unified principle for analyzing and improving the performance of the transfer process. Three field synergy numbers are introduced for heat, mass, and momentum transfer, respectively, and three cases are demonstrated for validation. The results indicate that the field synergy numbers will increase when reducing the angle between the velocity vector and the temperature gradient or the species concentration gradient fields in the convective heat or mass transfer, and the overall heat or mass transfer capability is therefore enhanced. In fluid flows, it will reduce the fluid flow drag to decrease the synergy number between the velocity and the velocity gradient fields over the entire domain and to decrease the product between the fluid viscosity and the velocity gradient at the boundary simultaneously.

  14. Generational Differences in Work-Family Conflict and Synergy

    Directory of Open Access Journals (Sweden)

    Nicholas J. Beutell

    2013-06-01

    Full Text Available This paper examines differences in work-family conflict and synergy among the four generational groups represented in the contemporary workforce: Generation Y Generation X, Baby Boomers, and Matures using data from the 2008 National Study of the Changing Workforce (n = 3,502. Significant generational differences were found for work-family conflict (work interfering with family and family interfering with work but not for work-family synergy. Mental health and job pressure were the best predictors of work interfering with family conflict for each generational group. Work-family synergy presented a more complex picture. Work-family conflict and synergy were significantly related to job, marital, and life satisfaction. Implications and directions for future research are discussed.

  15. Future Combat Systems (FCS) Creates Cannon and Mortar Synergy

    National Research Council Canada - National Science Library

    Beard, Kirby; James, Jeff; Tolbert, Vincent J

    2008-01-01

    .... The NLOS-C is one of the eight MGVs. Program Manager FCS (Brigade Combat Team (PM FCS(BCT)) is leveraging previous and current research and development efforts to create synergy between cannons and mortars, without duplication of effort...

  16. Generational differences in work-family conflict and synergy.

    Science.gov (United States)

    Beutell, Nicholas J

    2013-06-19

    This paper examines differences in work-family conflict and synergy among the four generational groups represented in the contemporary workforce: Generation Y Generation X, Baby Boomers, and Matures using data from the 2008 National Study of the Changing Workforce (n = 3,502). Significant generational differences were found for work-family conflict (work interfering with family and family interfering with work) but not for work-family synergy. Mental health and job pressure were the best predictors of work interfering with family conflict for each generational group. Work-family synergy presented a more complex picture. Work-family conflict and synergy were significantly related to job, marital, and life satisfaction. Implications and directions for future research are discussed.

  17. Ethnic diversity and knowledge synergies: Rethinking the interrelations

    DEFF Research Database (Denmark)

    Lauring, Jakob

    2005-01-01

    desire to see ethnical diversity as productive. Theoretical reviews and empirical research have indicated that the link between diversity and knowledge synergy cannot be taken for granted. This article argues that some theoretical rethinking of managerial strategies toward cultural diversity...

  18. Generational Differences in Work-Family Conflict and Synergy

    Science.gov (United States)

    Beutell, Nicholas J.

    2013-01-01

    This paper examines differences in work-family conflict and synergy among the four generational groups represented in the contemporary workforce: Generation Y Generation X, Baby Boomers, and Matures using data from the 2008 National Study of the Changing Workforce (n = 3,502). Significant generational differences were found for work-family conflict (work interfering with family and family interfering with work) but not for work-family synergy. Mental health and job pressure were the best predictors of work interfering with family conflict for each generational group. Work-family synergy presented a more complex picture. Work-family conflict and synergy were significantly related to job, marital, and life satisfaction. Implications and directions for future research are discussed. PMID:23783221

  19. The efficacy of Elekta Synergy image-guided radiotherapy

    International Nuclear Information System (INIS)

    Takamatsu, Shigeyuki; Takanaka, Tsuyoshi; Kumano, Tomoyasu

    2008-01-01

    We evaluated the efficacy of Elekta Synergy image-guided radiotherapy (IGRT) system equipped with cone beam CT (CBCT) for high accuracy radiation therapy. In cases set up with body marking who had large set up error could be adjusted by this system within 1 mm error. IGRT with CBCT correction provided precise set up. Elekta Synergy IGRT system is useful for high accuracy set up and will facilitate novel precise radiotherapy techniques. (author)

  20. Generational Differences in Work-Family Conflict and Synergy

    OpenAIRE

    Beutell, Nicholas

    2013-01-01

    This paper examines differences in work-family conflict and synergy among the four generational groups represented in the contemporary workforce: Generation Y Generation X, Baby Boomers, and Matures using data from the 2008 National Study of the Changing Workforce (n = 3,502). Significant generational differences were found for work-family conflict (work interfering with family and family interfering with work) but not for work-family synergy. Mental health and job pressure were the best pred...

  1. Synergy optimization and operation management on syndicate complementary knowledge cooperation

    Science.gov (United States)

    Tu, Kai-Jan

    2014-10-01

    The number of multi enterprises knowledge cooperation has grown steadily, as a result of global innovation competitions. I have conducted research based on optimization and operation studies in this article, and gained the conclusion that synergy management is effective means to break through various management barriers and solve cooperation's chaotic systems. Enterprises must communicate system vision and access complementary knowledge. These are crucial considerations for enterprises to exert their optimization and operation knowledge cooperation synergy to meet global marketing challenges.

  2. Solar + Storage Synergies for Managing Commercial-Customer Demand Charges

    Energy Technology Data Exchange (ETDEWEB)

    Gagnon, Pieter J. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Govindarajan, Anand [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bird, Lori A. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, Naim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-10-24

    We study the synergies between behind-the-meter solar and storage in reducing commercial-customer demand charges. This follows two previous studies that examined demand charge savings for stand-alone solar in both the residential and commercial sectors. In this study we show that solar and storage show consistent synergies for demand charge management, that the magnitude of reductions are highly customer-specific, and that the magnitude of savings is influenced by the design of the electricity tariff.

  3. Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication

    Directory of Open Access Journals (Sweden)

    Chih-Chun Wen

    2011-10-01

    Full Text Available Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (龍膽 lóng dǎn; the dried rhizome of Gentiana scabra, Dioscoreae Rhizoma (山藥 shān yào; the tuber of Dioscorea batatas, Cassiae Semen (決明子 jué míng zǐ; the dried seed of Cassia tora and Loranthi Ramus (桑寄生 sāng jì shēng; the dried stem, with leaf of Taxillus chinensis (designated as GSH, DBM, CTH and TCH, respectively, and two from Rhizoma Cibotii (狗脊 gǒu jǐ; the dried rhizome of Cibotium barometz (designated as CBE and CBM, were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50 and 50% of viral replication (EC50 were determined. The resulting selective index values (SI=CC50/EC50 of the most effective extracts CBE, GSH, DBM, CTH and TCH were>59.4,> 57.5,> 62.1,> 59.4, and>92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39 μg/ml and 44 μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics.

  4. E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity

    International Nuclear Information System (INIS)

    Vlasak, R.; Luytjes, W.; Leider, J.; Spaan, W.; Palese, P.

    1988-01-01

    In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with [ 3 H]DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the esterase/receptor-destroying activity of BCV is associated with the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possible during virus entry or uncoating

  5. The Middle East respiratory syndrome coronavirus (MERS-CoV does not replicate in Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Emmie de Wit

    Full Text Available In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.

  6. E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity

    Energy Technology Data Exchange (ETDEWEB)

    Vlasak, R.; Luytjes, W.; Leider, J.; Spaan, W.; Palese, P.

    1988-12-01

    In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with (/sup 3/H)DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the esterase/receptor-destroying activity of BCV is associated with the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possible during virus entry or uncoating.

  7. Nuclear energy and its synergies with renewable energies; Le nucleaire dans ses synergies avec les renouvelables

    Energy Technology Data Exchange (ETDEWEB)

    Carre, F. [CEA Saclay, DEN, 91 - Gif-sur-Yvette (France); Mermilliod, N. [CEA Grenoble, Dir. de la Recherche Technologique, 38 (France); Devezeaux De Lavergne, J.G. [CEA Saclay, Dir. de l' Institut de tecchnico-economie des systemes energetiques I-tese, 91 - Gif-sur-Yvette (France); Durand, S. [CEA Grenoble, European Institute of Technology -KIC InnoEnergy, 38 (France)

    2011-05-15

    France has the ambition to become a world leader in both nuclear industry and in renewable energies. 3 types of synergies between nuclear power and renewable energies are highlighted. First, nuclear power can be used as a low-carbon energy to produce the equipment required to renewable energy production for instance photovoltaic cells. Secondly, to benefit from the complementary features of both energies: continuous/intermittency of the production, centralized/local production. The future development of smart grids will help to do that. Thirdly, to use nuclear energy to produce massively hydrogen from water and synthetic fuels from biomass. (A.C.)

  8. Global mental health and neuroscience: potential synergies.

    Science.gov (United States)

    Stein, Dan J; He, Yanling; Phillips, Anthony; Sahakian, Barbara J; Williams, John; Patel, Vikram

    2015-02-01

    Global mental health has emerged as an important specialty. It has drawn attention to the burden of mental illness and to the relative gap in mental health research and services around the world. Global mental health has raised the question of whether this gap is a developmental issue, a health issue, a human rights issue, or a combination of these issues-and it has raised awareness of the need to develop new approaches for building capacity, mobilising resources, and closing the research and treatment gap. Translational neuroscience has also advanced. It comprises an important conceptual approach to understanding the neurocircuitry and molecular basis of mental disorders, to rethinking how best to undertake research on the aetiology, assessment, and treatment of these disorders, with the ultimate aim to develop entirely new approaches to prevention and intervention. Some apparent contrasts exist between these fields; global mental health emphasises knowledge translation, moving away from the bedside to a focus on health systems, whereas translational neuroscience emphasises molecular neuroscience, focusing on transitions between the bench and bedside. Meanwhile, important opportunities exist for synergy between the two paradigms, to ensure that present opportunities in mental health research and services are maximised. Here, we review the approaches of global mental health and clinical neuroscience to diagnosis, pathogenesis, and intervention, and make recommendations for facilitating an integration of these two perspectives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Achieving biopolymer synergy in systems chemistry.

    Science.gov (United States)

    Bai, Yushi; Chotera, Agata; Taran, Olga; Liang, Chen; Ashkenasy, Gonen; Lynn, David G

    2018-05-31

    Synthetic and materials chemistry initiatives have enabled the translation of the macromolecular functions of biology into synthetic frameworks. These explorations into alternative chemistries of life attempt to capture the versatile functionality and adaptability of biopolymers in new orthogonal scaffolds. Information storage and transfer, however, so beautifully represented in the central dogma of biology, require multiple components functioning synergistically. Over a single decade, the emerging field of systems chemistry has begun to catalyze the construction of mutualistic biopolymer networks, and this review begins with the foundational small-molecule-based dynamic chemical networks and peptide amyloid-based dynamic physical networks on which this effort builds. The approach both contextualizes the versatile approaches that have been developed to enrich chemical information in synthetic networks and highlights the properties of amyloids as potential alternative genetic elements. The successful integration of both chemical and physical networks through β-sheet assisted replication processes further informs the synergistic potential of these networks. Inspired by the cooperative synergies of nucleic acids and proteins in biology, synthetic nucleic-acid-peptide chimeras are now being explored to extend their informational content. With our growing range of synthetic capabilities, structural analyses, and simulation technologies, this foundation is radically extending the structural space that might cross the Darwinian threshold for the origins of life as well as creating an array of alternative systems capable of achieving the progressive growth of novel informational materials.

  10. Muscle synergy extraction during arm reaching movements at different speeds.

    Science.gov (United States)

    Sabzevari, Vahid Reza; Jafari, Amir Homayoun; Boostani, Reza

    2017-01-01

    Muscle synergy is the activation of a group of muscles that contribute to a particular movement. The goal of the present study is to examine the hypothesis that human reaching movements at different speeds share similar muscle synergies and to investigate the kinesiology basis and innervation of muscles. Electromyographic activity from six muscles of the upper limb and shoulder girdle were recorded during three movements at different speeds, i.e. slow, moderate and fast. The effect of window length on the RMS signal of the EMG was analyzed and then EMG envelope signals were decomposed using non-negative matrix factorization. For each of the ten subjects, three synergies were extracted which accounted for at least 99% of the VAF. For each movement, the muscle synergies and muscle activation coefficients of all participants were clustered in to three partitions. Investigation showed a high similarity and dependency of cluster members due to the cosine similarity and mutual information in muscle synergy clustering. For further verification, the EMG envelope signals for all subjects were reconstructed. The results indicated a lower reconstruction error using the center of the muscle synergy clusters in comparison with the average of the activation coefficients, which confirms the current research's hypothesis.

  11. What is synergy? The Saariselkä agreement revisited.

    Science.gov (United States)

    Tang, Jing; Wennerberg, Krister; Aittokallio, Tero

    2015-01-01

    Many biological or chemical agents when combined interact with each other and produce a synergistic response that cannot be predicted based on the single agent responses alone. However, depending on the postulated null hypothesis of non-interaction, one may end up in different interpretations of synergy. Two popular reference models for null hypothesis include the Bliss independence model and the Loewe additivity model, each of which is formulated from different perspectives. During the last century, there has been an intensive debate on the suitability of these synergy models, both of which are theoretically justified and also in practice supported by different schools of scientists. More than 20 years ago, there was a community effort to make a consensus on the terminology one should use when claiming synergy. The agreement was formulated at a conference held in Saariselkä, Finland in 1992, stating that one should use the terms Bliss synergy or Loewe synergy to avoid ambiguity in the underlying models. We review the theoretical relationships between these models and argue that one should combine the advantages of both models to provide a more consistent definition of synergy and antagonism.

  12. Factors Influencing Emergency Nurses' Burnout During an Outbreak of Middle East Respiratory Syndrome Coronavirus in Korea

    OpenAIRE

    Kim, Ji Soo; Choi, Jeong Sil

    2016-01-01

    Purpose: Emergency department (ED) nurses suffer from persistent stress after experiencing the traumatic event of exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), which can subsequently lead to burnout. This study aimed to assess ED nurses' burnout level during an outbreak of MERS-CoV and to identify influencing factors in order to provide basic information for lowering and preventing the level of burnout. Methods: Study participants were ED nurses working in eight hosp...

  13. Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture.

    OpenAIRE

    Harrison , Sally; Tarpey , Ian; Rothwell , Lisa; Kasier , Pete; Hiscox , Julian

    2007-01-01

    Abstract The avian coronavirus infectious bronchitis virus (IBV) is a major economic pathogen of domestic poultry which, despite vaccination, causes mortality and significant losses in production. During replication of the RNA genome there is a high frequency of mutation and recombination which has given rise to many strains of IBV and results in the potential for new and emerging strains. Currently the live-attenuated vaccine gives poor cross strain immunity. Effective antivira...

  14. Discovery of a novel canine respiratory coronavirus support genetic recombination among betacoronavirus1.

    Science.gov (United States)

    Lu, Shuai; Wang, Yanqun; Chen, Yingzhu; Wu, Bingjie; Qin, Kun; Zhao, Jincun; Lou, Yongliang; Tan, Wenjie

    2017-06-02

    Although canine respiratory coronavirus (CRCoV) is an important respiratory pathogen that is prevalent in many countries, only one complete genome sequence of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses and recombination have rarely been conducted, as small numbers of samples and limited genomic characterization have previously prevented further analyses. Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based on complete genome of all available coronaviruses consistently show that CRCoV BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV, forming a separate clade that split off early from other Betacoronavirus 1. Based on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S) gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV-B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage around the world for a long time. Recombinant events among Betacoronavirus 1 may have implications for CRCoV transmissibility. All these findings provide further information regarding the origin of CRCoV. Copyright © 2017. Published by Elsevier B.V.

  15. Genome-wide analysis of codon usage bias in Bovine Coronavirus

    OpenAIRE

    Castells, Mat?as; Victoria, Mat?as; Colina, Rodney; Musto, H?ctor; Cristina, Juan

    2017-01-01

    Background Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host?s immune system and evolution. Methods We performed a comprehensive analysis of co...

  16. Inactivation of surrogate coronaviruses on hard surfaces by health care germicides.

    Science.gov (United States)

    Hulkower, Rachel L; Casanova, Lisa M; Rutala, William A; Weber, David J; Sobsey, Mark D

    2011-06-01

    In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  17. Bovine coronavirus in naturally andexperimentally exposed calves; viralshedding and the potential for transmission

    OpenAIRE

    Oma, Veslemøy Sunniva; Tråven, Madeleine; Alenius, S.; Myrmel, Mette; Stokstad, Maria

    2016-01-01

    Background Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis t...

  18. Genetic diversity of bats coronaviruses in the Atlantic Forest hotspot biome, Brazil.

    Science.gov (United States)

    Góes, Luiz Gustavo Bentim; Campos, Angélica Cristine de Almeida; Carvalho, Cristiano de; Ambar, Guilherme; Queiroz, Luzia Helena; Cruz-Neto, Ariovaldo Pereira; Munir, Muhammad; Durigon, Edison Luiz

    2016-10-01

    Bats are notorious reservoirs of genetically-diverse and high-profile pathogens, and are playing crucial roles in the emergence and re-emergence of viruses, both in human and in animals. In this report, we identified and characterized previously unknown and diverse genetic clusters of bat coronaviruses in the Atlantic Forest Biome, Brazil. These results highlight the virus richness of bats and their possible roles in the public health. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts.

    Science.gov (United States)

    Okusaga, Olaoluwa; Yolken, Robert H; Langenberg, Patricia; Lapidus, Manana; Arling, Timothy A; Dickerson, Faith B; Scrandis, Debra A; Severance, Emily; Cabassa, Johanna A; Balis, Theodora; Postolache, Teodor T

    2011-04-01

    Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson's χ² tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic symptoms during mood episodes. Seropositivity for influenza A (p=0.004), B (pmood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p=0.001) and history of psychotic symptoms (p=0.005). The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Coronavirus in Pigs: Significance and Presentation of Swine Epidemic Diarrhea Virus (PEDV in Colombia

    Directory of Open Access Journals (Sweden)

    Ricardo Piñeros

    2015-05-01

    Full Text Available The article seeks to study general aspects of the main coronaviruses affecting pigs, their presentation in Colombia, and particular aspects of porcine epidemic diarrhea virus (PEDV, emerging in different countries and generating a great impact on the health and economy of the swine industry. The main coronaviruses affecting swine are porcine transmissible gastroenteritis virus (TGEV, porcine respiratory coronavirus (PRCV, porcine hemagglutinating encephalomyelitis virus (PHEV, PEDV, and porcine deltacoronavirus (PDCoV. Long ago in Colombia there had been reports of TGEV and PRCV associated with the importation of animals from the United States, which was controlled in the infected farms and in quarantine units. PEDV was first detected in Colombia in mid-March 2014; the Colombian Agricultural Institute issued a health alert in Neiva (Huila, Fusagasugá and Silvania (Cundinamarca, and Puerto López (Meta due to the unusual presentation of epidemic vomiting and diarrhea in young and adult animals, abortion in pregnant sows, with high mortality rates (up to 100% in animals during the first week of age. At present the disease has been reported in other municipalities of the country as well as in different countries with similar clinical conditions and mortality rates in pigs with high economic losses for the swine sector.

  1. Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.

    Science.gov (United States)

    Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi

    2017-02-01

    Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis-transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis-transisomerase active sites of Cyps might be required for FCoV replication.

  2. Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function.

    Science.gov (United States)

    Jaimes, Javier A; Whittaker, Gary R

    2018-04-01

    Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). The FCoV spike (S) protein is considered the viral regulator for binding and entry to the cell. This protein is also involved in FCoV tropism and virulence, as well as in the switch from enteric disease to FIP. This regulation is carried out by spike's major functions: receptor binding and virus-cell membrane fusion. In this review, we address important aspects in FCoV genetics, replication and pathogenesis, focusing on the role of S. To better understand this, FCoV S protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63) S structure. We describe the specific structural characteristics of the FCoV S, in comparison with other coronavirus spikes. We also revise the biochemical events needed for FCoV S activation and its relation to the structural features of the protein. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

    Science.gov (United States)

    Licitra, Beth N.; Millet, Jean K.; Regan, Andrew D.; Hamilton, Brian S.; Rinaldi, Vera D.; Duhamel, Gerald E.

    2013-01-01

    Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses. PMID:23763835

  4. Feline Coronavirus 3c Protein: A Candidate for a Virulence Marker?

    Directory of Open Access Journals (Sweden)

    A. S. Hora

    2016-01-01

    Full Text Available Feline infectious peritonitis virus (FIPV is highly virulent and responsible for the highly fatal disease feline infectious peritonitis (FIP, whereas feline enteric coronavirus (FECV is widespread among the feline population and typically causes asymptomatic infections. Some candidates for genetic markers capable of differentiating these two pathotypes of a unique virus (feline coronavirus have been proposed by several studies. In the present survey, in order to search for markers that can differentiate FECV and FIPV, several clones of the 3a–c, E, and M genes were sequenced from samples obtained from cats with or without FIP. All genes showed genetic diversity and suggested the presence of FCoV mutant spectrum capable of producing a virulent pathotype in an individual-specific way. In addition, all the feline coronavirus FIPV strains demonstrated a truncated 3c protein, and the 3c gene was the only observed pathotypic marker for FCoVs, showing that 3c gene is a candidate marker for the distinction between the two pathotypes when the mutant spectrum is taken into account.

  5. Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

    Science.gov (United States)

    Weber, David J; Rutala, William A; Fischer, William A; Kanamori, Hajime; Sickbert-Bennett, Emily E

    2016-05-02

    Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Use of SAR data for proliferation monitoring

    International Nuclear Information System (INIS)

    Lafitte, M.; Robin, J.P.

    2013-01-01

    Synthetic Aperture Radar (SAR) is an active and coherent system. SAR images are complex data which contain both amplitude and phase information. The analysis of single SAR data required a very good experience and a good understanding of SAR geometry regarding layover, shadowing, texture and speckle. Image analyst can depicts and describes most of the facilities related to nuclear proliferation and weapons of mass destruction (WMD). The Amplitude Change Detection (ACD) technique consists of a combination of two or three SAR amplitude data acquired with similar orbit and frequency parameters on different dates. That technique provides a very good overview of the changes and particularly regarding vehicles activity and constructions ongoing within the area of interest over the monitoring period. One of the particularities of the SAR systems is to be coherent. The phase of a single image is not exploitable. Thus when two or more SAR data have been acquired with identical orbit and frequency parameters, the phases shift are indicators of changes such as structural changes, terrain subsidence or motion. The Multi-Temporal Coherence (MTC) product merged the two type of information previously detailed: the ACD and coherence analysis. It consists of the combination of two amplitude images and the corresponding coherence computed image. The MTC image may highlights changes between two states of a target which on the ACD analysis appeared unchanged. EUSC uses the difference interferometry techniques in order to estimate volumes that have changed between two acquisition dates. The paper is followed by the slides of the presentation. (A.C.)

  7. Synergy for a Strong Future FY 2008

    International Nuclear Information System (INIS)

    Devore, L.; Chrzanowski, P.

    2008-01-01

    Lawrence Livermore National Security, LLC is committed to delivering the best combination of scientific research, technology development, business management, and safe, secure operations in support of Lawrence Livermore National Laboratory's critical national security mission. LLNS was formed specifically to manage LLNL for the Department of Energy's National Nuclear Security Administration. LLNS consists of a team of five organizations renowned for their expertise and accomplishments throughout the U.S. nuclear weapons complex and beyond - Bechtel National, University of California, Babcock and Wilcox, Washington Division of URS Corporation, and Battelle. Bechtel is the nation's largest engineering and construction firm and a leader in project management. The University of California is the world's largest public research institution. Babcock and Wilcox and the Washington Division of URS Corporation are top nuclear facilities contractors and between them manage four of DOE's five safest sites. Battelle is a global leader in science and technology development and commercialization. The LLNS Board of Governors provides oversight for the management of the Laboratory and holds the Director and LLNS President responsible for the Laboratory's performance. The Board has seven standing committees that assist in assessing Laboratory performance and monitoring risks and internal controls. Through the Board of Governors, the Laboratory can reach back to LLNS partner organizations to help ensure that it fulfills its national security mission with excellence in scientific research, technology development, business management, and safe, secure operations. LLNS assumed management of LLNL on October 1, 2007. This report highlights LLNS accomplishments in FY2008, its first year as the Laboratory's managing contractor. It is clear that LLNS and the Laboratory have exploited numerous synergies inherent in their relationship - for example, science and engineering, mission and

  8. Cleavage of group 1 coronavirus spike proteins: how furin cleavage is traded off against heparan sulfate binding upon cell culture adaptation

    NARCIS (Netherlands)

    Haan, de C.A.M.; Haijema, B.J.; Schellen, P.; Wichgers Schreur, P.J.; Lintelo, te E.; Vennema, H.; Rottier, P.J.M.

    2008-01-01

    A longstanding enigmatic feature of the group 1 coronaviruses is the uncleaved phenotype of their spike protein, an exceptional property among class I fusion proteins. Here, however, we show that some group 1 coronavirus spike proteins carry a furin enzyme recognition motif and can actually be

  9. Lack of association between infection with a novel human coronavirus (HCoV), HCoV-NH, and Kawasaki disease in Taiwan

    NARCIS (Netherlands)

    Chang, Luan-Yin; Chiang, Bor-Luen; Kao, Chuan-Liang; Wu, Mei-Hwan; Chen, Pei-Jer; Berkhout, Ben; Yang, Hui-Ching; Huang, Li-Min

    2006-01-01

    We investigated whether infection with a novel human coronavirus (HCoV), called "New Haven coronavirus" (HCoV-NH)--which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63--is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were

  10. Dissection of protein interactomics highlights microRNA synergy.

    Science.gov (United States)

    Zhu, Wenliang; Zhao, Yilei; Xu, Yingqi; Sun, Yong; Wang, Zhe; Yuan, Wei; Du, Zhimin

    2013-01-01

    Despite a large amount of microRNAs (miRNAs) have been validated to play crucial roles in human biology and disease, there is little systematic insight into the nature and scale of the potential synergistic interactions executed by miRNAs themselves. Here we established an integrated parameter synergy score to determine miRNA synergy, by combining the two mechanisms for miRNA-miRNA interactions, miRNA-mediated gene co-regulation and functional association between target gene products, into one single parameter. Receiver operating characteristic (ROC) analysis indicated that synergy score accurately identified the gene ontology-defined miRNA synergy (AUC = 0.9415, psynergy, implying poor expectancy of widespread synergy. However, targeting more key genes made two miRNAs more likely to act synergistically. Compared to other miRNAs, miR-21 was a highly exceptional case due to frequent appearance in the top synergistic miRNA pairs. This result highlighted its essential role in coordinating or strengthening physiological and pathological functions of other miRNAs. The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis. The novel approach established in this study enables easy and effective identification of condition-restricted potent miRNA synergy simply by concentrating the available protein interactomics and miRNA-target interaction data into a single parameter synergy score. Our results may be important for understanding synergistic gene regulation by miRNAs and may have significant implications for miRNA combination therapy of cardiovascular disease.

  11. Prehension synergies and control with referent hand configurations.

    Science.gov (United States)

    Latash, Mark L; Friedman, Jason; Kim, Sun Wook; Feldman, Anatol G; Zatsiorsky, Vladimir M

    2010-04-01

    We used the framework of the equilibrium-point hypothesis (in its updated form based on the notion of referent configuration) to investigate the multi-digit synergies at two levels of a hypothetical hierarchy involved in prehensile actions. Synergies were analyzed at the thumb-virtual finger (VF) level (VF is an imaginary digit with the mechanical action equivalent to that of the four actual fingers) and at the individual finger level. The subjects performed very quick vertical movements of a handle into a target. A load could be attached off-center to provide a pronation or supination torque. In a few trials, the handle was unexpectedly fixed to the table and the digits slipped off the sensors. In such trials, the hand stopped at a higher vertical position and rotated into pronation or supination depending on the expected torque. The aperture showed non-monotonic changes with a large, fast decrease and further increase, ending up with a smaller distance between the thumb and the fingers as compared to unperturbed trials. Multi-digit synergies were quantified using indices of co-variation between digit forces and moments of force across unperturbed trials. Prior to the lifting action, high synergy indices were observed at the individual finger level while modest indices were observed at the thumb-VF level. During the lifting action, the synergies at the individual finger level disappeared while the synergy indices became higher at the thumb-VF level. The results support the basic premise that, within a given task, setting a referent configuration may be described with a few referent values of variables that influence the equilibrium state, to which the system is attracted. Moreover, the referent configuration hypothesis can help interpret the data related to the trade-off between synergies at different hierarchical levels.

  12. TerraSAR-X InSAR multipass analysis on Venice, Italy)

    Science.gov (United States)

    Nitti, D. O.; Nutricato, R.; Bovenga, F.; Refice, A.; Chiaradia, M. T.; Guerriero, L.

    2009-09-01

    The TerraSAR-X (copyright) mission, launched in 2007, carries a new X-band Synthetic Aperture Radar (SAR) sensor optimally suited for SAR interferometry (InSAR), thus allowing very promising application of InSAR techniques for the risk assessment on areas with hydrogeological instability and especially for multi-temporal analysis, such as Persistent Scatterer Interferometry (PSI) techniques, originally developed at Politecnico di Milano. The SPINUA (Stable Point INterferometry over Unurbanised Areas) technique is a PSI processing methodology which has originally been developed with the aim of detection and monitoring of coherent PS targets in non or scarcely-urbanized areas. The main goal of the present work is to describe successful applications of the SPINUA PSI technique in processing X-band data. Venice has been selected as test site since it is in favorable settings for PSI investigations (urban area containing many potential coherent targets such as buildings) and in view of the availability of a long temporal series of TerraSAR-X stripmap acquisitions (27 scenes in all). The Venice Lagoon is affected by land sinking phenomena, whose origins are both natural and man-induced. The subsidence of Venice has been intensively studied for decades by determining land displacements through traditional monitoring techniques (leveling and GPS) and, recently, by processing stacks of ERS/ENVISAT SAR data. The present work is focused on an independent assessment of application of PSI techniques to TerraSAR-X stripmap data for monitoring the stability of the Venice area. Thanks to its orbital repeat cycle of only 11 days, less than a third of ERS/ENVISAT C-band missions, the maximum displacement rate that can be unambiguously detected along the Line-of-Sight (LOS) with TerraSAR-X SAR data through PSI techniques is expected to be about twice the corresponding value of ESA C-band missions, being directly proportional to the sensor wavelength and inversely proportional to the

  13. Accelerated Scientific InSAR Processing, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Neva Ridge Technologies proposes to develop a suite of software tools for the analysis of SAR and InSAR data, focused on having a robust and adopted capability well...

  14. Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

    Directory of Open Access Journals (Sweden)

    Manabu Watanabe

    2010-01-01

    Full Text Available We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR σ∘ under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the σ∘ difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that σ∘ and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

  15. Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

    Directory of Open Access Journals (Sweden)

    Shimada Masanobu

    2010-01-01

    Full Text Available Abstract We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

  16. Infrastructure monitoring with spaceborne SAR sensors

    CERN Document Server

    ANGHEL, ANDREI; CACOVEANU, REMUS

    2017-01-01

    This book presents a novel non-intrusive infrastructure monitoring technique based on the detection and tracking of scattering centers in spaceborne SAR images. The methodology essentially consists of refocusing each available SAR image on an imposed 3D point cloud associated to the envisaged infrastructure element and identifying the reliable scatterers to be monitored by means of four dimensional (4D) tomography. The methodology described in this book provides a new perspective on infrastructure monitoring with spaceborne SAR images, is based on a standalone processing chain, and brings innovative technical aspects relative to conventional approaches. The book is intended primarily for professionals and researchers working in the area of critical infrastructure monitoring by radar remote sensing.

  17. Explosive spreading on complex networks: The role of synergy.

    Science.gov (United States)

    Liu, Quan-Hui; Wang, Wei; Tang, Ming; Zhou, Tao; Lai, Ying-Cheng

    2017-04-01

    In spite of the vast literature on spreading dynamics on complex networks, the role of local synergy, i.e., the interaction of elements that when combined produce a total effect greater than the sum of the individual elements, has been studied but only for irreversible spreading dynamics. Reversible spreading dynamics are ubiquitous but their interplay with synergy has remained unknown. To fill this knowledge gap, we articulate a model to incorporate local synergistic effect into the classical susceptible-infected-susceptible process, in which the probability for a susceptible node to become infected through an infected neighbor is enhanced when the neighborhood of the latter contains a number of infected nodes. We derive master equations incorporating the synergistic effect, with predictions that agree well with the numerical results. A striking finding is that when a parameter characterizing the strength of the synergy reinforcement effect is above a critical value, the steady-state density of the infected nodes versus the basic transmission rate exhibits an explosively increasing behavior and a hysteresis loop emerges. In fact, increasing the synergy strength can promote the spreading and reduce the invasion and persistence thresholds of the hysteresis loop. A physical understanding of the synergy promoting explosive spreading and the associated hysteresis behavior can be obtained through a mean-field analysis.

  18. PRF Ambiguity Detrmination for Radarsat ScanSAR System

    Science.gov (United States)

    Jin, Michael Y.

    1998-01-01

    PRF ambiguity is a potential problem for a spaceborne SAR operated at high frequencies. For a strip mode SAR, there were several approaches to solve this problem. This paper, however, addresses PRF ambiguity determination algorithms suitable for a burst mode SAR system such as the Radarsat ScanSAR. The candidate algorithms include the wavelength diversity algorithm, range look cross correlation algorithm, and multi-PRF algorithm.

  19. Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23

    Directory of Open Access Journals (Sweden)

    Patrick C. Y. Woo

    2016-05-01

    Full Text Available Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23 from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3% and 59 (100% of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001. Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV, respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1.

  20. Resource synergy in stream periphyton communities

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Walter [University of Illinois, Urbana-Champaign; Fanta, S.E. [University of Illinois; Roberts, Brian J [ORNL; Francoeur, Steven N. [Eastern Michigan University, Ypsilanti, MI

    2011-03-01

    1. Light and nutrients play pivotal roles in determining the growth of autotrophs, yet the potential for synergistic interactions between the two resources in algal communities is poorly understood, especially in stream ecosystems. In this study, light and phosphorus were manipulated in large experimental streams to examine resource colimitation and synergy in stream periphyton. 2. Whole-stream metabolism was simultaneously limited by light and phosphorus. Increasing the supply of either light or phosphorus resulted in significant increases in primary production and the transformation of the streams from heterotrophy to autotrophy. 3. Resource-driven changes in periphyton community structure occurred in concert with changes in production. Algal assemblages in highly shaded streams were composed primarily of small diatoms such as Achnanthidium minutissima, whereas larger diatoms such as Melosira varians predominated at higher irradiances. Phosphorus enrichment had relatively little effect on assemblage structure, but it did substantially diminish the abundance of Meridion circulare, a diatom whose mucilaginous colonies were conspicuously abundant in phosphorus-poor, high-light streams. Bacterial biomass declined relative to algal biomass with increases in primary productivity, regardless of whether the increases were caused by light or phosphorus. 4. Synergistic effects on primary production appeared to occur because the availability of one resource facilitated the utilization of the other. Light increased the abundance of large diatoms, which are known to convert high concentrations of nutrients into primary production more effectively than smaller taxa. Phosphorus enrichment led to the replacement of Meridion circulare by non-mucilaginous taxa in phosphorus-enriched streams, and we hypothesize that this change enabled more efficient use of light in photosynthesis. Higher ratios of chlorophyll a : biomass in phosphorus-enriched streams may have also led to more

  1. SARS Risk Perception, Knowledge, Precautions, and Information Sources, the Netherlands

    Science.gov (United States)

    Aro, Arja R.; Oenema, Anke; de Zwart, Onno; Richardus, Jan Hendrik; Bishop, George D.

    2004-01-01

    Severe acute respiratory syndrome (SARS)–related risk perceptions, knowledge, precautionary actions, and information sources were studied in the Netherlands during the 2003 SARS outbreak. Although respondents were highly aware of the SARS outbreak, the outbreak did not result in unnecessary precautionary actions or fears. PMID:15496256

  2. Science data collection with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Woelders, Kim; Madsen, Søren Nørvang

    1996-01-01

    Discusses examples on the use of polarimetric SAR in a number of Earth science studies. The studies are presently being conducted by the Danish Center for Remote Sensing. A few studies of the European Space Agency's EMAC programme are also discussed. The Earth science objectives are presented......, and the potential of polarimetric SAR is discussed and illustrated with data collected by the Danish airborne EMISAR system during a number of experiments in 1994 and 1995. The presentation will include samples of data acquired for the different studies...

  3. Satellite sar detection of hurricane helene (2006)

    DEFF Research Database (Denmark)

    Ju, Lian; Cheng, Yongcun; Xu, Qing

    2013-01-01

    In this paper, the wind structure of hurricane Helene (2006) over the Atlantic Ocean is investigated from a C-band RADARSAT-1 synthetic aperture radar (SAR) image acquired on 20 September 2006. First, the characteristics, e.g., the center, scale and area of the hurricane eye (HE) are determined. ...... observations from the stepped frequency microwave radiometer (SFMR) on NOAA P3 aircraft. All the results show the capability of hurricane monitoring by satellite SAR. Copyright © 2013 by the International Society of Offshore and Polar Engineers (ISOPE)....

  4. The planned Alaska SAR Facility - An overview

    Science.gov (United States)

    Carsey, Frank; Weeks, Wilford

    1987-01-01

    The Alaska SAR Facility (ASF) is described in an overview fashion. The facility consists of three major components, a Receiving Ground System, a SAR Processing System and an Analysis and Archiving System; the ASF Program also has a Science Working Team and the requisite management and operations systems. The ASF is now an approved and fully funded activity; detailed requirements and science background are presented for the facility to be implemented for data from the European ERS-1, the Japanese ERS-1 and Radarsat.

  5. Geologic mapping in Greenland with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Madsen, Søren Nørvang; Brooks, C. K.

    1995-01-01

    The application of synthetic aperture radar (SAR) for geologic mapping in Greenland is investigated by the Danish Center for Remote Sensing (DCRS) in co-operation with the Danish Lithosphere Centre (DLC). In 1994 a pilot project was conducted in East Greenland. The Danish airborne SAR, EMISAR...... mapping is complicated by an extreme topography leading to massive shadowing, foreshortening and layover. An artifact characterised by high cross-polarisation is observed behind many sharp mountain ridges. A multi-reflection hypothesis has been investigated without finding the ultimate proof...

  6. Cultural effect on synergy realization in cross-border acquisitions

    DEFF Research Database (Denmark)

    Wang, Daojuan; Hain, Daniel; Dao, Li Thuy

    2017-01-01

    This study examines two levels of cultural differences - national and organizational on synergy realization simultaneously by considering two critical implementation factors as the moderators: pre-acquisition due diligence and post-acquisition coordination efforts. Meanwhile, we argue cultural...... by Nordic companies. Results show that both national and organizational cultural differences only exert negative impact on realization of Type-2 synergy which is more implicit/intangible, less predictable, usually tacit-knowledge intensive and/or complementary, but no impact on realization of Type-1 synergy...... which is explicit/tangible, more predictable, less tacit-knowledge intensive, and/or based on cost reduction and similarity. Meanwhile, national cultural differences generate stronger negative effect at higher level of significance than that of organizational cultural differences. Moreover, proactive...

  7. The quest for synergy when developing the urban fringe

    DEFF Research Database (Denmark)

    Hansen, Jesper Rohr; Engberg, Lars A.

    How can planning policies related to urban fringe development and disadvantaged neighbourhoods create synergy? This question is approached and answered by various research fields and explored on various urban-planning levels, displaying case-studies related to urban regeneration, post......-industrial and suburban development and urban fringe literature. The present paper adds to these discussions by analysing two case-studies in Denmark in which local government pursue traditional urban-growth strategies in urban-fringe development - a post-industrial harbour and a large suburb, located just outside...... analyses this synergy by first describing the legislative, interventionist and financial context for urban-growth strategies deployed in the cases. On this background, the paper explores synergy potential related to policy as well as private-sector actors (local businesses, social housing organizations...

  8. Handwriting: three-dimensional kinetic synergies in circle drawing movements.

    Science.gov (United States)

    Hooke, Alexander W; Karol, Sohit; Park, Jaebum; Kim, Yoon Hyuk; Shim, Jae Kun

    2012-07-01

    The purpose of this study was to investigate central nervous system (CNS) strategies for controlling multifinger forces during a circle-drawing task. Subjects drew 30 concentric, discontinuous clockwise and counter clockwise circles, at self and experimenter-set paces. The three-dimensional trajectory of the pen's center of mass and the three-dimensional forces and moments of force at each contact between the hand and the pen were recorded. Uncontrolled Manifold Analysis was used to quantify the synergies between pen-hand contact forces in radial, tangential and vertical directions. Results showed that synergies in the radial and tangential components were significantly stronger than in the vertical component. Synergies in the clockwise direction were significantly stronger than the counterclockwise direction in the radial and vertical components. Pace was found to be insignificant under any condition.

  9. Nuclear and Renewable Energy Synergies Workshop: Report of Proceedings

    International Nuclear Information System (INIS)

    Ruth, M.; Antkowiak, M.; Gossett, S.

    2011-01-01

    Two of the major challenges the U.S. energy sector faces are greenhouse gas emissions and oil that is both imported and potentially reaching a peak (the point at which maximum extraction is reached). Interest in development of both renewable and nuclear energy has been strong because both have potential for overcoming these challenges. Research in both energy sources is ongoing, but relatively little research has focused on the potential benefits of combining nuclear and renewable energy. In September 2011, the Joint Institute for Strategic Energy Analysis (JISEA) convened the Nuclear and Renewable Energy Synergies Workshop at the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) to identify potential synergies and strategic leveraging opportunities between nuclear energy and renewable energy. Industry, government, and academic thought leaders gathered to identify potential broad categories of synergies and brainstorm topic areas for additional analysis and research and development (R and D). This report records the proceedings and outcomes of the workshop.

  10. Computational modeling of the bat HKU4 coronavirus 3CLpro inhibitors as a tool for the development of antivirals against the emerging Middle East respiratory syndrome (MERS) coronavirus.

    Science.gov (United States)

    Abuhammad, Areej; Al-Aqtash, Rua'a A; Anson, Brandon J; Mesecar, Andrew D; Taha, Mutasem O

    2017-11-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that poses a major challenge to clinical management. The 3C-like protease (3CL pro ) is essential for viral replication and thus represents a potential target for antiviral drug development. Presently, very few data are available on MERS-CoV 3CL pro inhibition by small molecules. We conducted extensive exploration of the pharmacophoric space of a recently identified set of peptidomimetic inhibitors of the bat HKU4-CoV 3CL pro . HKU4-CoV 3CL pro shares high sequence identity (81%) with the MERS-CoV enzyme and thus represents a potential surrogate model for anti-MERS drug discovery. We used 2 well-established methods: Quantitative structure-activity relationship (QSAR)-guided modeling and docking-based comparative intermolecular contacts analysis. The established pharmacophore models highlight structural features needed for ligand recognition and revealed important binding-pocket regions involved in 3CL pro -ligand interactions. The best models were used as 3D queries to screen the National Cancer Institute database for novel nonpeptidomimetic 3CL pro inhibitors. The identified hits were tested for HKU4-CoV and MERS-CoV 3CL pro inhibition. Two hits, which share the phenylsulfonamide fragment, showed moderate inhibitory activity against the MERS-CoV 3CL pro and represent a potential starting point for the development of novel anti-MERS agents. To the best of our knowledge, this is the first pharmacophore modeling study supported by in vitro validation on the MERS-CoV 3CL pro . MERS-CoV is an emerging virus that is closely related to the bat HKU4-CoV. 3CL pro is a potential drug target for coronavirus infection. HKU4-CoV 3CL pro is a useful surrogate model for the identification of MERS-CoV 3CL pro enzyme inhibitors. dbCICA is a very robust modeling method for hit identification. The phenylsulfonamide scaffold represents a potential starting point for MERS coronavirus 3CL pro inhibitors

  11. Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

    Directory of Open Access Journals (Sweden)

    Anna Lundin

    2014-05-01

    Full Text Available 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.

  12. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

    Science.gov (United States)

    Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-12-01

    One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

  13. Synergy Maps: exploring compound combinations using network-based visualization.

    Science.gov (United States)

    Lewis, Richard; Guha, Rajarshi; Korcsmaros, Tamás; Bender, Andreas

    2015-01-01

    The phenomenon of super-additivity of biological response to compounds applied jointly, termed synergy, has the potential to provide many therapeutic benefits. Therefore, high throughput screening of compound combinations has recently received a great deal of attention. Large compound libraries and the feasibility of all-pairs screening can easily generate large, information-rich datasets. Previously, these datasets have been visualized using either a heat-map or a network approach-however these visualizations only partially represent the information encoded in the dataset. A new visualization technique for pairwise combination screening data, termed "Synergy Maps", is presented. In a Synergy Map, information about the synergistic interactions of compounds is integrated with information about their properties (chemical structure, physicochemical properties, bioactivity profiles) to produce a single visualization. As a result the relationships between compound and combination properties may be investigated simultaneously, and thus may afford insight into the synergy observed in the screen. An interactive web app implementation, available at http://richlewis42.github.io/synergy-maps, has been developed for public use, which may find use in navigating and filtering larger scale combination datasets. This tool is applied to a recent all-pairs dataset of anti-malarials, tested against Plasmodium falciparum, and a preliminary analysis is given as an example, illustrating the disproportionate synergism of histone deacetylase inhibitors previously described in literature, as well as suggesting new hypotheses for future investigation. Synergy Maps improve the state of the art in compound combination visualization, by simultaneously representing individual compound properties and their interactions. The web-based tool allows straightforward exploration of combination data, and easier identification of correlations between compound properties and interactions.

  14. SARS knowledge, perceptions, and behaviors: a comparison between Finns and the Dutch during the SARS outbreak in 2003

    NARCIS (Netherlands)

    Vartti, A.M.; Oenema, A.; Schreck, M.; Uutela, A.; Zwart, de O.; Brug, J.; Aro, A.R.

    2009-01-01

    BACKGROUND: The SARS outbreak served to test both local and international outbreak management and risk communication practices. PURPOSE: The study compares SARS knowledge, perceptions, behaviors, and information between Finns and the Dutch during the SARS outbreak in 2003. METHOD: The participants

  15. Design and realization of an active SAR calibrator for TerraSAR-X

    Science.gov (United States)

    Dummer, Georg; Lenz, Rainer; Lutz, Benjamin; Kühl, Markus; Müller-Glaser, Klaus D.; Wiesbeck, Werner

    2005-10-01

    TerraSAR-X is a new earth observing satellite which will be launched in spring 2006. It carries a high resolution X-band SAR sensor. For high image data quality, accurate ground calibration targets are necessary. This paper describes a novel system concept for an active and highly integrated, digitally controlled SAR system calibrator. A total of 16 active transponder and receiver systems and 17 receiver only systems will be fabricated for a calibration campaign. The calibration units serve for absolute radiometric calibration of the SAR image data. Additionally, they are equipped with an extra receiver path for two dimensional satellite antenna pattern recognition. The calibrator is controlled by a dedicated digital Electronic Control Unit (ECU). The different voltages needed by the calibrator and the ECU are provided by the third main unit called Power Management Unit (PMU).

  16. Synergy in spreading processes: from exploitative to explorative foraging strategies.

    Science.gov (United States)

    Pérez-Reche, Francisco J; Ludlam, Jonathan J; Taraskin, Sergei N; Gilligan, Christopher A

    2011-05-27

    An epidemiological model which incorporates synergistic effects that allow the infectivity and/or susceptibility of hosts to be dependent on the number of infected neighbors is proposed. Constructive synergy induces an exploitative behavior which results in a rapid invasion that infects a large number of hosts. Interfering synergy leads to a slower and sparser explorative foraging strategy that traverses larger distances by infecting fewer hosts. The model can be mapped to a dynamical bond percolation with spatial correlations that affect the mechanism of spread but do not influence the critical behavior of epidemics. © 2011 American Physical Society

  17. Synergies between renewable energy and fresh water production. Scoping study

    Energy Technology Data Exchange (ETDEWEB)

    Geurts, F.; Noothout, P.; Schaap, A. [Ecofys Netherlands, Utrecht (Netherlands)

    2011-02-15

    The IEA Implementing Agreement for Renewable Energy Technology Deployment (IEA-RETD) investigated the opportunities for coupling renewable energy systems with fresh water supply systems. The four main conclusions of the scoping study, carried out by Ecofys, are: (1) Fresh water production based on desalination technologies provide most options for synergies with renewable energy production; (2) Linking desalination to renewable sources is currently not economically viable; (3) There is a large potential for small scale (decentralised) desalination plants; (4) Current commercially-sized desalination technologies are in need of a constant operation point. Reverse osmosis and thermal membrane technologies might give future synergies as deferrable load.

  18. SAR Image Classification Based on Its Texture Features

    Institute of Scientific and Technical Information of China (English)

    LI Pingxiang; FANG Shenghui

    2003-01-01

    SAR images not only have the characteristics of all-ay, all-eather, but also provide object information which is different from visible and infrared sensors. However, SAR images have some faults, such as more speckles and fewer bands. The authors conducted the experiments of texture statistics analysis on SAR image features in order to improve the accuracy of SAR image interpretation.It is found that the texture analysis is an effective method for improving the accuracy of the SAR image interpretation.

  19. CFAR Edge Detector for Polarimetric SAR Images

    DEFF Research Database (Denmark)

    Schou, Jesper; Skriver, Henning; Nielsen, Allan Aasbjerg

    2003-01-01

    Finding the edges between different regions in an image is one of the fundamental steps of image analysis, and several edge detectors suitable for the special statistics of synthetic aperture radar (SAR) intensity images have previously been developed. In this paper, a new edge detector for polar...

  20. Discovery and SAR of hydantoin TACE inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wensheng; Guo, Zhuyan; Orth, Peter; Madison, Vincent; Chen, Lei; Dai, Chaoyang; Feltz, Robert J.; Girijavallabhan, Vinay M.; Kim, Seong Heon; Kozlowski, Joseph A.; Lavey, Brian J.; Li, Dansu; Lundell, Daniel; Niu, Xiaoda; Piwinski, John J.; Popovici-Muller, Janeta; Rizvi, Razia; Rosner, Kristin E.; Shankar, Bandarpalle B.; Shih, Neng-Yang; Siddiqui, M.A.; Sun, J.; Tong, L.; Umland, S.; Wong, M.K.; Yang, D.Y.; Zhou, G. (Merck)

    2010-09-03

    We disclose inhibitors of TNF-{alpha} converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.

  1. Relevant Scatterers Characterization in SAR Images

    Science.gov (United States)

    Chaabouni, Houda; Datcu, Mihai

    2006-11-01

    Recognizing scenes in a single look meter resolution Synthetic Aperture Radar (SAR) images, requires the capability to identify relevant signal signatures in condition of variable image acquisition geometry, arbitrary objects poses and configurations. Among the methods to detect relevant scatterers in SAR images, we can mention the internal coherence. The SAR spectrum splitted in azimuth generates a series of images which preserve high coherence only for particular object scattering. The detection of relevant scatterers can be done by correlation study or Independent Component Analysis (ICA) methods. The present article deals with the state of the art for SAR internal correlation analysis and proposes further extensions using elements of inference based on information theory applied to complex valued signals. The set of azimuth looks images is analyzed using mutual information measures and an equivalent channel capacity is derived. The localization of the "target" requires analysis in a small image window, thus resulting in imprecise estimation of the second order statistics of the signal. For a better precision, a Hausdorff measure is introduced. The method is applied to detect and characterize relevant objects in urban areas.

  2. Digital demodulator for wide bandwidth SAR

    DEFF Research Database (Denmark)

    Jørgensen, Jørn Hjelm

    2000-01-01

    A novel approach to the design of efficient digital quadrature demodulators for wide bandwidth SAR systems is described. Efficiency is obtained by setting the intermediate frequency to 1/4 the ADC sampling frequency. One channel is made filter-free by synchronizing the local oscillator...

  3. Offshore wind mapping Mediterranean area using SAR

    DEFF Research Database (Denmark)

    Calaudi, Rosamaria; Arena, Felice; Badger, Merete

    2013-01-01

    Satellite observations of the ocean surface, for example from Synthetic Aperture Radars (SAR), provide information about the spatial wind variability over large areas. This is of special interest in the Mediterranean Sea, where spatial wind information is only provided by sparse buoys, often with...

  4. The Seamless SAR Archive (SSARA) Project and Other SAR Activities at UNAVCO

    Science.gov (United States)

    Baker, S.; Crosby, C. J.; Meertens, C. M.; Fielding, E. J.; Bryson, G.; Buechler, B.; Nicoll, J.; Baru, C.

    2014-12-01

    The seamless synthetic aperture radar archive (SSARA) implements a seamless distributed access system for SAR data and derived data products (i.e. interferograms). SSARA provides a unified application programming interface (API) for SAR data search and results at the Alaska Satellite Facility and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives. Interest from the international community has prompted an effort to incorporate ESA's Virtual Archive 4 Geohazard Supersites and Natural Laboratories (GSNL) collections and other archives into the federated query service. SSARA also provides Digital Elevation Model access for topographic correction via a simple web service through OpenTopography and tropospheric correction products through JPL's OSCAR service. Additionally, UNAVCO provides data storage capabilities for WInSAR PIs with approved TerraSAR-X and ALOS-2 proposals which allows easier distribution to US collaborators on associated proposals and facilitates data access through the SSARA web services. Further work is underway to incorporate federated data discovery for GSNL across SAR, GPS, and seismic datasets provided by web services from SSARA, GSAC, and COOPEUS.

  5. Isolation of avian infectious bronchitis coronavirus from domestic peafowl (Pavo cristatus) and teal (Anas).

    Science.gov (United States)

    Liu, Shengwang; Chen, Jianfei; Chen, Jinding; Kong, Xiangang; Shao, Yuhao; Han, Zongxi; Feng, Li; Cai, Xuehui; Gu, Shoulin; Liu, Ming

    2005-03-01

    Coronavirus-like viruses, designated peafowl/China/LKQ3/2003 (pf/CH/LKQ3/03) and teal/China/LDT3/2003 (tl/CH/LDT3/03), were isolated from a peafowl and a teal during virological surveillance in Guangdong province, China. Partial genomic sequence analysis showed that these isolates had the S-3-M-5-N gene order that is typical of avian coronaviruses. The spike, membrane and nucleocapsid protein genes of pf/CH/LKQ3/03 had >99 % identity to those of the avian infectious bronchitis coronavirus H120 vaccine strain (Massachusetts serotype) and other Massachusetts serotype isolates. Furthermore, when pf/CH/LKQ3/03 was inoculated experimentally into chickens (specific-pathogen-free), no disease signs were apparent. tl/CH/LDT3/03 had a spike protein gene with 95 % identity to that of a Chinese infectious bronchitis virus (IBV) isolate, although more extensive sequencing revealed the possibility that this strain may have undergone recombination. When inoculated into chickens, tl/CH/LDT3/03 resulted in the death of birds from nephritis. Taken together, this information suggests that pf/CH/LKQ3/03 might be a revertant, attenuated vaccine IBV strain, whereas tl/CH/LDT3/03 is a nephropathogenic field IBV strain, generated through recombination. The replication and non-pathogenic nature of IBV in domestic peafowl and teal under field conditions raises questions as to the role of these hosts as carriers of IBV and the potential that they may have to transmit virus to susceptible chicken populations.

  6. Establishment of feline intestinal epithelial cell cultures for the propagation and study of feline enteric coronaviruses

    Science.gov (United States)

    2013-01-01

    Feline infectious peritonitis (FIP) is the most feared infectious cause of death in cats, induced by feline infectious peritonitis virus (FIPV). This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV). To date, feline coronavirus (FCoV) research has been hampered by the lack of susceptible cell lines for the propagation of serotype I FCoVs. In this study, long-term feline intestinal epithelial cell cultures were established from primary ileocytes and colonocytes by simian virus 40 (SV40) T-antigen- and human Telomerase Reverse Transcriptase (hTERT)-induced immortalization. Subsequently, these cultures were evaluated for their usability in FCoV research. Firstly, the replication capacity of the serotype II strains WSU 79–1683 and WSU 79–1146 was studied in the continuous cultures as was done for the primary cultures. In accordance with the results obtained in primary cultures, FCoV WSU 79–1683 still replicated significantly more efficient compared to FCoV WSU 79–1146 in both continuous cultures. In addition, the cultures were inoculated with faecal suspensions from healthy cats and with faecal or tissue suspensions from FIP cats. The cultures were susceptible to infection with different serotype I enteric strains and two of these strains were further propagated. No infection was seen in cultures inoculated with FIPV tissue homogenates. In conclusion, a new reliable model for FCoV investigation and growth of enteric field strains was established. In contrast to FIPV strains, FECVs showed a clear tropism for intestinal epithelial cells, giving an explanation for the observation that FECV is the main pathotype circulating among cats. PMID:23964891

  7. Spaceborne Differential SAR Interferometry: Data Analysis Tools for Deformation Measurement

    Directory of Open Access Journals (Sweden)

    Michele Crosetto

    2011-02-01

    Full Text Available This paper is focused on spaceborne Differential Interferometric SAR (DInSAR for land deformation measurement and monitoring. In the last two decades several DInSAR data analysis procedures have been proposed. The objective of this paper is to describe the DInSAR data processing and analysis tools developed at the Institute of Geomatics in almost ten years of research activities. Four main DInSAR analysis procedures are described, which range from the standard DInSAR analysis based on a single interferogram to more advanced Persistent Scatterer Interferometry (PSI approaches. These different procedures guarantee a sufficient flexibility in DInSAR data processing. In order to provide a technical insight into these analysis procedures, a whole section discusses their main data processing and analysis steps, especially those needed in PSI analyses. A specific section is devoted to the core of our PSI analysis tools: the so-called 2+1D phase unwrapping procedure, which couples a 2D phase unwrapping, performed interferogram-wise, with a kind of 1D phase unwrapping along time, performed pixel-wise. In the last part of the paper, some examples of DInSAR results are discussed, which were derived by standard DInSAR or PSI analyses. Most of these results were derived from X-band SAR data coming from the TerraSAR-X and CosmoSkyMed sensors.

  8. SAR Raw Data Generation for Complex Airport Scenes

    Directory of Open Access Journals (Sweden)

    Jia Li

    2014-10-01

    Full Text Available The method of generating the SAR raw data of complex airport scenes is studied in this paper. A formulation of the SAR raw signal model of airport scenes is given. Via generating the echoes from the background, aircrafts and buildings, respectively, the SAR raw data of the unified SAR imaging geometry is obtained from their vector additions. The multipath scattering and the shadowing between the background and different ground covers of standing airplanes and buildings are analyzed. Based on the scattering characteristics, coupling scattering models and SAR raw data models of different targets are given, respectively. A procedure is given to generate the SAR raw data of airport scenes. The SAR images from the simulated raw data demonstrate the validity of the proposed method.

  9. ANALYSIS OF MULTIPATH PIXELS IN SAR IMAGES

    Directory of Open Access Journals (Sweden)

    J. W. Zhao

    2016-06-01

    Full Text Available As the received radar signal is the sum of signal contributions overlaid in one single pixel regardless of the travel path, the multipath effect should be seriously tackled as the multiple bounce returns are added to direct scatter echoes which leads to ghost scatters. Most of the existing solution towards the multipath is to recover the signal propagation path. To facilitate the signal propagation simulation process, plenty of aspects such as sensor parameters, the geometry of the objects (shape, location, orientation, mutual position between adjacent buildings and the physical parameters of the surface (roughness, correlation length, permittivitywhich determine the strength of radar signal backscattered to the SAR sensor should be given in previous. However, it's not practical to obtain the highly detailed object model in unfamiliar area by field survey as it's a laborious work and time-consuming. In this paper, SAR imaging simulation based on RaySAR is conducted at first aiming at basic understanding of multipath effects and for further comparison. Besides of the pre-imaging simulation, the product of the after-imaging, which refers to radar images is also taken into consideration. Both Cosmo-SkyMed ascending and descending SAR images of Lupu Bridge in Shanghai are used for the experiment. As a result, the reflectivity map and signal distribution map of different bounce level are simulated and validated by 3D real model. The statistic indexes such as the phase stability, mean amplitude, amplitude dispersion, coherence and mean-sigma ratio in case of layover are analyzed with combination of the RaySAR output.

  10. New challenges for a SAR toolbox

    International Nuclear Information System (INIS)

    Loreaux, P.; Quin, G.

    2013-01-01

    High resolution multi-frequency synthetic aperture radar (SAR) imagery, available since early 2008, brings all weather capability and day/night operability in support of safeguards verification. Today, a combined approach of high resolution optical and radar imagery in monitoring exercise would enable looking at any area of interest on daily basis. One of the challenges is the co-registration of SAR images acquired with different acquisition mode and also with different optical images. We show in this paper the on-going research work to find a general co-register method and an automatic tool to detect changes. Before having an operational co-register tool, a method to find automatically tie points between SAR images acquired with different acquisition mode and with optical images has to be developed. Concerning an automatic change detection method we can conclude that the study of the Harmonic mean, Geometric mean and Arithmetic mean, enables several applications like change detection for SAR imagery. Thus, we developed the MAGMA (Method for Arithmetic and Geometric Means Analysis) change detection method. As shown in this paper, the MAGMA method improves the Maximum Likelihood techniques like GLRT, using Information-Theory concepts to detect changes between SAR amplitude images. The major improvement consists in a lower false detection rate, especially in low amplitude areas. The second improvement consists in a better location of the changes in clearly delimited areas, which enables precise interpretations. Results presented here reveal the potential of high resolution radar imagery for a baseline description of some sites, change detection based on repeat pass imagery acquisitions and site specific constraints in coherent change detection due to cover conditions. (A.C.)

  11. Cooperation of an RNA Packaging Signal and a Viral Envelope Protein in Coronavirus RNA Packaging

    OpenAIRE

    Narayanan, Krishna; Makino, Shinji

    2001-01-01

    Murine coronavirus mouse hepatitis virus (MHV) produces a genome-length mRNA, mRNA 1, and six or seven species of subgenomic mRNAs in infected cells. Among these mRNAs, only mRNA 1 is efficiently packaged into MHV particles. MHV N protein binds to all MHV mRNAs, whereas envelope M protein interacts only with mRNA 1. This M protein-mRNA 1 interaction most probably determines the selective packaging of mRNA 1 into MHV particles. A short cis-acting MHV RNA packaging signal is necessary and suffi...

  12. Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning

    Directory of Open Access Journals (Sweden)

    Atkins John F

    2010-01-01

    Full Text Available Abstract Background Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community. Results Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae, Reoviridae, Rhabdoviridae and Coronaviridae, respectively.

  13. Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

    Science.gov (United States)

    Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

    2012-04-02

    This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

  14. syNErgy: A Case Study in Workforce Curriculum Development

    Science.gov (United States)

    Killingsworth, John; Grosskopf, Kevin R.

    2013-01-01

    With high unemployment and structural changes to industry, workforce development in the United States is a growing concern. Many semiskilled workers lack knowledge, skills, and abilities to be competitive for reemployment to green jobs. Nebraska's syNErgy research grant was introduced to address the training needs of unemployed and underemployed…

  15. Practice effects on intra-team synergies in football teams.

    Science.gov (United States)

    Silva, Pedro; Chung, Dante; Carvalho, Thiago; Cardoso, Tiago; Davids, Keith; Araújo, Duarte; Garganta, Júlio

    2016-04-01

    Developing synchronised player movements for fluent competitive match play is a common goal for coaches of team games. An ecological dynamics approach advocates that intra-team synchronization is governed by locally created information, which specifies shared affordances responsible for synergy formation. To verify this claim we evaluated coordination tendencies in two newly-formed teams of recreational players during association football practice games, weekly, for fifteen weeks (thirteen matches). We investigated practice effects on two central features of synergies in sports teams - dimensional compression and reciprocal compensation here captured through near in-phase modes of coordination and time delays between coupled players during forward and backwards movements on field while attacking and defending. Results verified that synergies were formed and dissolved rapidly as a result of the dynamic creation of informational properties, perceived as shared affordances among performers. Practising once a week led to small improvements in the readjustment delays between co-positioning team members, enabling faster regulation of coordinated team actions. Mean values of the number of player and team synergies displayed only limited improvements, possibly due to the timescales of practice. No relationship between improvements in dimensional compression and reciprocal compensation were found for number of shots, amount of ball possession and number of ball recoveries made. Findings open up new perspectives for monitoring team coordination processes in sport. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Synergies of multiple remote sensing data sources for REDD+ monitoring

    NARCIS (Netherlands)

    Sy, de V.; Herold, M.; Achard, F.; Asner, G.P.; Held, A.; Kellndorfer, J.; Verbesselt, J.

    2012-01-01

    Remote sensing technologies can provide objective, practical and cost-effective solutions for developing and maintaining REDD+ monitoring systems. This paper reviews the potential and status of available remote sensing data sources with a focus on different forest information products and synergies

  17. Academic Entrepreneurship and Traditional Academic Duties: Synergy or Rivalry?

    Science.gov (United States)

    De Silva, Muthu

    2016-01-01

    This study investigates the influence of academic entrepreneurship on traditional academic duties carried out in a resource-constrained environment, particularly focusing on whether there is synergy or rivalry between these two activities. Using qualitative evidence, we discover that there are funding, resource, knowledge and skill and networking…

  18. Possible causes of dry pea synergy to corn

    Science.gov (United States)

    Dry pea improves corn yield and tolerance to weed interference compared with soybean, spring wheat, or canola as preceding crops. To understand this synergy between dry pea and corn, we examined growth and nutrient concentration of corn following dry pea or soybean in sequence. Each corn plot was ...

  19. The synergy of creativity and critical thinking in engineering design

    DEFF Research Database (Denmark)

    Spuzic, Sead; Narayanan, Ramadas; Adriansen, Hanne Kirstine

    2016-01-01

    framework. It has been widely recognised that engineering design encompasses two ways of thinkingdcreative and critical. A central argument that the synergy of creativity and criticality is significantly enhanced by connecting true interdisciplinary augmentation with the fine arts is discussed along...

  20. Co-location synergies : specialized versus diverse logistics concentration areas

    NARCIS (Netherlands)

    Heuvel, van den F.P.; Langen, de P.W.; Donselaar, van K.H.; Fransoo, J.C.

    2012-01-01

    Purpose: The purpose of this paper is to contribute to the understanding of spatial concentration of logistics firms by empirically analyzing synergies through co-location and investigating whether co-location of logistics establishments in specialized logistics concentration areas results in

  1. Proximity matters : synergies through co-location of logistics establishments

    NARCIS (Netherlands)

    Heuvel, van den F.P.; Langen, de P.W.; Donselaar, van K.H.; Fransoo, J.C.

    2012-01-01

    Purpose: The purpose of this paper is to contribute to the understanding of spatial concentration of logistics firms by empirically analyzing synergies through co-location and investigating whether spatial concentration of logistics activities indeed results in classical agglomeration economies as

  2. A measure of internal synergy of the collective system

    Directory of Open Access Journals (Sweden)

    Novikov V.A.

    2013-12-01

    Full Text Available Background: The authors examine the methodology of HRM personnel management based on ratings. Proposed to represent a collective system that uses a matrix of pair relations as a system of linear differential equations. The condition of auto generation of an autonomous system can be determined by the application of the Laplace transformation to the system. This condition mainly depends on the main eigenvalue of dating relationships matrix. Assuming the oscillation frequency is straightly proportional to the system's synergy rating, a special algorithm of comparative evaluation of several collective systems was suggested. Methods: The calculation of the rating of internal synergies is based on the representation of the collective system as a system of linear differential equations, the coefficients of which are obtained by questionnaire survey of all members of the team. Internal representation of the system's synergism as a stimulation of an autonomous system allows using the eigenvector of the system as a measure of internal synergies. Results: The result of this method is the rating of members of interacting collective systems in terms of their contribution to the self-organization sharing behavior.  Conclusions:  Using a matrix of pair relations allows without direct programming and only using MathCad determines the measure of internal synergy of a collective system.  

  3. Human and veterinary medicine: the priority for public health synergies

    Directory of Open Access Journals (Sweden)

    Adriano Mantovani

    2008-12-01

    Full Text Available The concepts of ‘one medicine’ and 'one ‘health’ are supported and visualised as a tree (medicine, placed on the fertile soil (basic sciences, which divides into the two major branches of human and veterinary medicine, connected by the large branch of public health; minor branches (specialisations depart from the three larger ones. The synergy between human and veterinary medicine is not only a must for public health, but also implies ethical considerations. The basic reasons requiring synergy are found in the common sharing of the environment, in the use of animal products by humans, in the common culture and in the many problems to be faced together. The long list of adversities requiring synergy is topped by zoonoses (intended both in the classic and in the extended sense and food safety that extends to many other items connected with nutrition, environment, human/animal coexistence and the management of public health; the entire quality of human life is affected. Human and veterinary medicine have a strong cultural background (many subject matters in common, but unfortunately the undergraduate and postgraduate education programme (with few important exceptions do not offer training in cooperation. The synergy between human and veterinary medicines is an indicator of 'good public health practice' and any obstacles to this collaboration should be identified and eliminated. The logo for a public health founded on synergy is drawn as an umbrella formed by the medical and veterinary activities, protecting the population (consumers and producers, the animals and their products and the environment from the possible adversities linked to health.

  4. Characterizing and estimating noise in InSAR and InSAR time series with MODIS

    Science.gov (United States)

    Barnhart, William D.; Lohman, Rowena B.

    2013-01-01

    InSAR time series analysis is increasingly used to image subcentimeter displacement rates of the ground surface. The precision of InSAR observations is often affected by several noise sources, including spatially correlated noise from the turbulent atmosphere. Under ideal scenarios, InSAR time series techniques can substantially mitigate these effects; however, in practice the temporal distribution of InSAR acquisitions over much of the world exhibit seasonal biases, long temporal gaps, and insufficient acquisitions to confidently obtain the precisions desired for tectonic research. Here, we introduce a technique for constraining the magnitude of errors expected from atmospheric phase delays on the ground displacement rates inferred from an InSAR time series using independent observations of precipitable water vapor from MODIS. We implement a Monte Carlo error estimation technique based on multiple (100+) MODIS-based time series that sample date ranges close to the acquisitions times of the available SAR imagery. This stochastic approach allows evaluation of the significance of signals present in the final time series product, in particular their correlation with topography and seasonality. We find that topographically correlated noise in individual interferograms is not spatially stationary, even over short-spatial scales (<10 km). Overall, MODIS-inferred displacements and velocities exhibit errors of similar magnitude to the variability within an InSAR time series. We examine the MODIS-based confidence bounds in regions with a range of inferred displacement rates, and find we are capable of resolving velocities as low as 1.5 mm/yr with uncertainties increasing to ∼6 mm/yr in regions with higher topographic relief.

  5. A novel computational framework for deducing muscle synergies from experimental joint moments

    Directory of Open Access Journals (Sweden)

    Anantharaman eGopalakrishnan

    2014-12-01

    Full Text Available Prior experimental studies have hypothesized the existence of a ‘muscle synergy’ based control scheme for producing limb movements and locomotion in vertebrates. Such synergies have been suggested to consist of fixed muscle grouping schemes with the co-activation of all muscles in a synergy resulting in limb movement. Quantitative representations of these groupings (termed muscle weightings and their control signals (termed synergy controls have traditionally been derived by the factorization of experimentally measured EMG. This study presents a novel approach for deducing these weightings and controls from inverse dynamic joint moments that are computed from an alternative set of experimental measurements – movement kinematics and kinetics. This technique was applied to joint moments for healthy human walking at 0.7 and 1.7 m/s, and two sets of ‘simulated’ synergies were computed based on two different criteria (1 synergies were required to minimize errors between experimental and simulated joint moments in a musculoskeletal model (pure-synergy solution (2 along with minimizing joint moment errors, synergies also minimized muscle activation levels (optimal-synergy solution. On comparing the two solutions, it was observed that the introduction of optimality requirements (optimal-synergy to a control strategy solely aimed at reproducing the joint moments (pure-synergy did not necessitate major changes in the muscle grouping within synergies or the temporal profiles of synergy control signals. Synergies from both the simulated solutions exhibited many similarities to EMG derived synergies from a previously published study, thus implying that the analysis of the two different types of experimental data reveals similar, underlying synergy structures.

  6. Differential expression of the MERS-coronavirus receptor in the upper respiratory tract of humans and dromedary camels

    NARCIS (Netherlands)

    Widagdo, W; Raj, V Stalin; Schipper, Debby; Kolijn, Kimberley; van Leenders, Geert J L H; Bosch, Berend J; Bensaid, Albert; Segalés, Joaquim; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koopmans, Marion P; van den Brand, Judith M A; Haagmans, Bart L

    Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor - dipeptidyl peptidase 4 (DPP4) - is expressed in the upper respiratory tract epithelium of camels but not

  7. Middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies

    NARCIS (Netherlands)

    F. Song (Fei); R. Fux (Robert); L.B.V. Provacia (Lisette); A. Volz (Asisa); M. Eickmann; S. Becker (Stephan); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); G. Suttera (Gerd)

    2013-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic

  8. Evaluation of bovine coronavirus antibody levels, virus shedding, and respiratory disease incidence throughout the beef cattle production cycle

    Science.gov (United States)

    Objective- Determine how levels of serum antibody to bovine coronavirus (BCV) are related to virus shedding patterns and respiratory disease incidence in beef calves at various production stages. Animals- 890 crossbred beef calves from four separately managed herds at the U.S. Meat Animal Research C...

  9. Clinico-epidemiological characteristics of acute respiratory infections caused by coronavirus OC43, NL63 and 229E.

    Science.gov (United States)

    Reina, J; López-Causapé, C; Rojo-Molinero, E; Rubio, R

    2014-12-01

    Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia : a nationwide, cross-sectional, serological study

    NARCIS (Netherlands)

    Müller, Marcel A; Meyer, Benjamin; Corman, Victor M; Al-Masri, Malak; Turkestani, Abdulhafeez; Ritz, Daniel; Sieberg, Andrea; Aldabbagh, Souhaib; Bosch, Berend-J; Lattwein, Erik; Alhakeem, Raafat F; Assiri, Abdullah M; Albarrak, Ali M; Al-Shangiti, Ali M; Al-Tawfiq, Jaffar A; Wikramaratna, Paul; Alrabeeah, Abdullah A; Drosten, Christian; Memish, Ziad A

    2015-01-01

    BACKGROUND: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such

  11. Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis.

    Science.gov (United States)

    Sharmin, Refat; Islam, Abul B M M K

    2016-01-01

    MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein's antigenic sites are found to be conserved with those in HKU4 and HKU5. This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity.

  12. Assembly of spikes into coronavirus particles is mediated by the carboxy-terminal domain of the spike protein

    NARCIS (Netherlands)

    Godeke, G J; de Haan, Cornelis A M; Rossen, J W; Vennema, H; Rottier, P J

    The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. Here we demonstrate that incorporation is mediated by the short carboxy-terminal segment comprising the transmembrane and

  13. Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions.

    Science.gov (United States)

    Rodak, L; Babiuk, L A; Acres, S D

    1982-07-01

    The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.

  14. Isolation and characterization of current human coronavirus strains in primary human epithelial cell cultures reveal differences in target cell tropism

    NARCIS (Netherlands)

    Dijkman, Ronald; Jebbink, Maarten F.; Koekkoek, Sylvie M.; Deijs, Martin; Jónsdóttir, Hulda R.; Molenkamp, Richard; Ieven, Margareta; Goossens, Herman; Thiel, Volker; van der Hoek, Lia

    2013-01-01

    The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in

  15. Spaceborne Polarimetric SAR Interferometry: Performance Analysis and Mission Concepts

    Directory of Open Access Journals (Sweden)

    Shane R. Cloude

    2005-12-01

    Full Text Available We investigate multichannel imaging radar systems employing coherent combinations of polarimetry and interferometry (Pol-InSAR. Such systems are well suited for the extraction of bio- and geophysical parameters by evaluating the combined scattering from surfaces and volumes. This combination leads to several important differences between the design of Pol-InSAR sensors and conventional single polarisation SAR interferometers. We first highlight these differences and then investigate the Pol-InSAR performance of two proposed spaceborne SAR systems (ALOS/PalSAR and TerraSAR-L operating in repeat-pass mode. For this, we introduce the novel concept of a phase tube which enables (1 a quantitative assessment of the Pol-InSAR performance, (2 a comparison between different sensor configurations, and (3 an optimization of the instrument settings for different Pol-InSAR applications. The phase tube may hence serve as an interface between system engineers and application-oriented scientists. The performance analysis reveals major limitations for even moderate levels of temporal decorrelation. Such deteriorations may be avoided in single-pass sensor configurations and we demonstrate the potential benefits from the use of future bi- and multistatic SAR interferometers.

  16. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Synthesis and processing of structural and intracellular proteins of two enteric coronaviruses

    International Nuclear Information System (INIS)

    Sardinia, L.M.

    1985-01-01

    The synthesis and processing of virus-specific proteins of two economically important enteric coronaviruses, bovine enteric coronavirus (BCV) and transmissible gastroenteritis virus (TGEV), were studied at the molecular level. To determine the time of appearance of virus-specific proteins, virus-infected cells were labeled with 35 S-methionine at various times during infection, immunoprecipitated with specific hyperimmune ascitic fluid, and analyzed by SDS-polyacrylamide gel electrophoresis. The peak of BCV protein synthesis was found to be at 12 hours postinfection (hpi). The appearance of all virus-specific protein was coordinated. In contrast, the peak of TGEV protein synthesis was at 8 hpi, but the nucleocapsid proteins was present as early as 4 hpi. Virus-infected cells were treated with tunicamycin to ascertain the types of glycosidic linkages of the glycoproteins. The peplomer proteins of both viruses were sensitive to inhibition by tunicamycin indicating that they possessed N-linked carbohydrates. The matrix protein of TGEV was similarly affected. The matrix protein of BCV, however, was resistant to tunicamycin treatment and, therefore, has O-linked carbohydrates. Only the nucleocapsid protein of both viruses is phosphorylated as detected by radiolabeling with 32 P-orthophosphate. Pulse-chase studies and comparison of intracellular and virion proteins were done to detect precursor-product relationships

  18. Biochemical and biophysical characterization of the transmissible gastroenteritis coronavirus fusion core

    International Nuclear Information System (INIS)

    Ma Guangpeng; Feng Youjun; Gao Feng; Wang Jinzi; Liu Cheng; Li Yijing

    2005-01-01

    Transmissible gastroenteritis coronavirus (TGEV) is one of the most destructive agents, responsible for the enteric infections that are lethal for suckling piglets, causing enormous economic loss to the porcine fostering industry every year. Although it has been known that TGEV spiker protein is essential for the viral entry for many years, the detail knowledge of the TGEV fusion protein core is still very limited. Here, we report that TGEV fusion core (HR1-SGGRGG-HR2), in vitro expressed in GST prokaryotic expression system, shares the typical properties of the trimer of coiled-coil heterodimer (six α-helix bundle), which has been confirmed by a combined series of biochemical and biophysical evidences including size exclusion chromatography (gel-filtration), chemical crossing, and circular diagram. The 3D homologous structure model presents its most likely structure, extremely similar to those of the coronaviruses documented. Taken together, TGEV spiker protein belongs to the class I fusion protein, characterized by the existence of two heptad-repeat (HR) regions, HR1 and HR2, and the present knowledge about the truncated TGEV fusion protein core may facilitate in the design of the small molecule or polypeptide drugs targeting the membrane fusion between TGEV and its host

  19. Novel coronaviruses, astroviruses, adenoviruses and circoviruses in insectivorous bats from northern China.

    Science.gov (United States)

    Han, H-J; Wen, H-L; Zhao, L; Liu, J-W; Luo, L-M; Zhou, C-M; Qin, X-R; Zhu, Y-L; Liu, M-M; Qi, R; Li, W-Q; Yu, H; Yu, X-J

    2017-12-01

    Bats are considered as the reservoirs of several emerging infectious disease, and novel viruses are continually found in bats all around the world. Studies conducted in southern China found that bats carried a variety of viruses. However, few studies have been conducted on bats in northern China, which harbours a diversity of endemic insectivorous bats. It is important to understand the prevalence and diversity of viruses circulating in bats in northern China. In this study, a total of 145 insectivorous bats representing six species were collected from northern China and screened with degenerate primers for viruses belonging to six families, including coronaviruses, astroviruses, hantaviruses, paramyxoviruses, adenoviruses and circoviruses. Our study found that four of the viruses screened for were positive and the overall detection rates for astroviruses, coronaviruses, adenoviruses and circoviruses in bats were 21.4%, 15.9%, 20% and 37.2%, respectively. In addition, we found that bats in northern China harboured a diversity of novel viruses. Common Serotine (Eptesicus serotinu), Fringed long-footed Myotis (Myotis fimriatus) and Peking Myotis (Myotis pequinius) were investigated in China for the first time. Our study provided new information on the ecology and phylogeny of bat-borne viruses. © 2017 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

  20. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

    2016-11-28

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

  1. Survey of feline leukemia virus and feline coronaviruses in captive neotropical wild felids from Southern Brazil.

    Science.gov (United States)

    Guimaraes, Ana M S; Brandão, Paulo E; de Moraes, Wanderlei; Cubas, Zalmir S; Santos, Leonilda C; Villarreal, Laura Y B; Robes, Rogério R; Coelho, Fabiana M; Resende, Mauricio; Santos, Renata C F; Oliveira, Rosangela C; Yamaguti, Mauricio; Marques, Lucas M; Neto, Renata L; Buzinhani, Melissa; Marques, Regina; Messick, Joanne B; Biondo, Alexander W; Timenetsky, Jorge

    2009-06-01

    A total of 57 captive neotropical felids (one Leopardus geoffroyi, 14 Leopardus pardalis, 17 Leopardus wiedii, 22 Leopardus tigrinus, and three Puma yagouaroundi) from the Itaipu Binacional Wildlife Research Center (Refúgio Bela Vista, Southern Brazil) were anesthetized for blood collection. Feces samples were available for 44 animals, including one L. geoffroyi, eight L. pardalis, 14 L. wiedii, 20 L. tigrinus, and one P. yagouaroundi. Total DNA and RNA were extracted from blood and feces, respectively, using commercial kits. Blood DNA samples were evaluated by polymerase chain reaction (PCR) for feline leukemia virus (FeLV) proviral DNA, whereas reverse transcriptase-PCR was run on fecal samples for detection of coronavirus RNA. None of the samples were positive for coronaviruses. A male L. pardalis and a female L. tigrinus were positive for FeLV proviral DNA, and identities of PCR products were confirmed by sequencing. This is the first evidence of FeLV proviral DNA in these species in Southern Brazil.

  2. Mutation of the S and 3c genes in genomes of feline coronaviruses.

    Science.gov (United States)

    Oguma, Keisuke; Ohno, Megumi; Yoshida, Mayuko; Sentsui, Hiroshi

    2018-05-17

    Feline coronavirus (FCoV) is classified into two biotypes based on its pathogenicity in cats: a feline enteric coronavirus of low pathogenicity and a highly virulent feline infectious peritonitis virus. It has been suspected that FCoV alters its biotype via mutations in the viral genome. The S and 3c genes of FCoV have been considered the candidates for viral pathogenicity conversion. In the present study, FCoVs were analyzed for the frequency and location of mutations in the S and 3c genes from faecal samples of cats in an animal shelter and the faeces, effusions, and tissues of cats that were referred to veterinary hospitals. Our results indicated that approximately 95% FCoVs in faeces did not carry mutations in the two genes. However, 80% FCoVs in effusion samples exhibited mutations in the S and 3c genes with remainder displaying a mutation in the S or 3c gene. It was also suggested that mutational analysis of the 3c gene could be useful for studying the horizontal transmission of FCoVs in multi-cat environments.

  3. Federated query services provided by the Seamless SAR Archive project

    Science.gov (United States)

    Baker, S.; Bryson, G.; Buechler, B.; Meertens, C. M.; Crosby, C. J.; Fielding, E. J.; Nicoll, J.; Youn, C.; Baru, C.

    2013-12-01

    The NASA Advancing Collaborative Connections for Earth System Science (ACCESS) seamless synthetic aperture radar (SAR) archive (SSARA) project is a 2-year collaboration between UNAVCO, the Alaska Satellite Facility (ASF), the Jet Propulsion Laboratory (JPL), and OpenTopography at the San Diego Supercomputer Center (SDSC) to design and implement a seamless distributed access system for SAR data and derived data products (i.e. interferograms). A major milestone for the first year of the SSARA project was a unified application programming interface (API) for SAR data search and results at ASF and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives (http://www.unavco.org/ws/brokered/ssara/sar/search). A command line client that utilizes this new service is provided as an open source utility for the community on GitHub (https://github.com/bakerunavco/SSARA). Further API development and enhancements added more InSAR specific keywords and quality control parameters (Doppler centroid, faraday rotation, InSAR stack size, and perpendicular baselines). To facilitate InSAR processing, the federated query service incorporated URLs for DEM (from OpenTopography) and tropospheric corrections (from the JPL OSCAR service) in addition to the URLs for SAR data. This federated query service will provide relevant QC metadata for selecting pairs of SAR data for InSAR processing and all the URLs necessary for interferogram generation. Interest from the international community has prompted an effort to incorporate other SAR data archives (the ESA Virtual Archive 4 and the DLR TerraSAR-X_SSC Geohazard Supersites and Natural Laboratories collections) into the federated query service which provide data for researchers outside the US and North America.

  4. Broad-Spectrum Inhibitors against 3C-Like Proteases of Feline Coronaviruses and Feline Caliciviruses

    Science.gov (United States)

    Shivanna, Vinay; Narayanan, Sanjeev; Prior, Allan M.; Weerasekara, Sahani; Hua, Duy H.; Kankanamalage, Anushka C. Galasiti; Groutas, William C.; Chang, Kyeong-Ok

    2015-01-01

    ABSTRACT Feline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities. IMPORTANCE Feline infectious peritonitis virus (FIPV) is the leading cause of death in young cats

  5. Estimating the Doppler centroid of SAR data

    DEFF Research Database (Denmark)

    Madsen, Søren Nørvang

    1989-01-01

    attractive properties. An evaluation based on an existing SEASAT processor is reported. The time-domain algorithms are shown to be extremely efficient with respect to requirements on calculations and memory, and hence they are well suited to real-time systems where the Doppler estimation is based on raw SAR......After reviewing frequency-domain techniques for estimating the Doppler centroid of synthetic-aperture radar (SAR) data, the author describes a time-domain method and highlights its advantages. In particular, a nonlinear time-domain algorithm called the sign-Doppler estimator (SDE) is shown to have...... data. For offline processors where the Doppler estimation is performed on processed data, which removes the problem of partial coverage of bright targets, the ΔE estimator and the CDE (correlation Doppler estimator) algorithm give similar performance. However, for nonhomogeneous scenes it is found...

  6. SAR Target Recognition via Supervised Discriminative Dictionary Learning and Sparse Representation of the SAR-HOG Feature

    Directory of Open Access Journals (Sweden)

    Shengli Song

    2016-08-01

    Full Text Available Automatic target recognition (ATR in synthetic aperture radar (SAR images plays an important role in both national defense and civil applications. Although many methods have been proposed, SAR ATR is still very challenging due to the complex application environment. Feature extraction and classification are key points in SAR ATR. In this paper, we first design a novel feature, which is a histogram of oriented gradients (HOG-like feature for SAR ATR (called SAR-HOG. Then, we propose a supervised discriminative dictionary learning (SDDL method to learn a discriminative dictionary for SAR ATR and propose a strategy to simplify the optimization problem. Finally, we propose a SAR ATR classifier based on SDDL and sparse representation (called SDDLSR, in which both the reconstruction error and the classification error are considered. Extensive experiments are performed on the MSTAR database under standard operating conditions and extended operating conditions. The experimental results show that SAR-HOG can reliably capture the structures of targets in SAR images, and SDDL can further capture subtle differences among the different classes. By virtue of the SAR-HOG feature and SDDLSR, the proposed method achieves the state-of-the-art performance on MSTAR database. Especially for the extended operating conditions (EOC scenario “Training 17 ∘ —Testing 45 ∘ ”, the proposed method improves remarkably with respect to the previous works.

  7. Premises and Limitations in Defining and Measuring Synergy from M&As

    Directory of Open Access Journals (Sweden)

    Aevoae George Marian

    2017-01-01

    Full Text Available Mergers and acquisitions are performed worldwide mainly because of synergy. Although many invoke the term synergy as the key motivation of why they engage in M&As, research has led us to understand that it is not very clear in terms of what it actually is. In the scientific literature, synergy is mostly defined as being “2+2=5”. Thus, we first thought that it can only be a positive effect. But, latter on, we found out that synergy is not only positive, it can be negative as well, known as negative synergy or dyssynergy. The purpose of this paper is to shed some light on what is synergy, how can we quantify and classify it and why acquiring firms tend to pay more for the target firm. We believe that there is a link between the amount of premium paid for a target firm and the expectations for synergy.

  8. Exo-exo synergy between Cel6A and Cel7A from Hypocrea jecorina

    DEFF Research Database (Denmark)

    Badino, Silke Flindt; Christensen, Stefan Jarl; Kari, Jeppe

    2017-01-01

    Synergy between cellulolytic enzymes is essential in both natural and industrial breakdown of biomass. In addition to synergy between endo- and exo-lytic enzymes, a lesser known but equally conspicuous synergy occurs among exo-acting, processive cellobiohydrolases (CBHs) such as Cel7A and Cel6A...... from Hypocrea jecorina. We studied this system using microcrystalline cellulose as substrate and found a degree of synergy between 1.3 and 2.2 depending on the experimental conditions. Synergy between enzyme variants without the carbohydrate binding module (CBM) and its linker was strongly reduced...... compared to the wild types. One plausible interpretation of this is that exo-exo synergy depends on the targeting role of the CBM. Many earlier works have proposed that exo-exo synergy was caused by an auxiliary endo-lytic activity of Cel6A. However, biochemical data from different assays suggested...

  9. Inter- and Intrasubject Similarity of Muscle Synergies During Bench Press With Slow and Fast Velocity.

    Science.gov (United States)

    Samani, Afshin; Kristiansen, Mathias

    2018-01-01

    We investigated the effect of low and high bar velocity on inter- and intrasubject similarity of muscle synergies during bench press. A total of 13 trained male subjects underwent two exercise conditions: a slow- and a fast-velocity bench press. Surface electromyography was recorded from 13 muscles, and muscle synergies were extracted using a nonnegative matrix factorization algorithm. The intrasubject similarity across conditions and intersubject similarity within conditions were computed for muscle synergy vectors and activation coefficients. Two muscle synergies were sufficient to describe the dataset variability. For the second synergy activation coefficient, the intersubject similarity within the fast-velocity condition was greater than the intrasubject similarity of the activation coefficient across the conditions. An opposite pattern was observed for the first muscle synergy vector. We concluded that the activation coefficients are robust within conditions, indicating a robust temporal pattern of muscular activity across individuals, but the muscle synergy vector seemed to be individually assigned.

  10. Simple test of synergy between ampicillin and vancomycin for resistant strains of Enterococcus faecium.

    Science.gov (United States)

    Green, M; Barbadora, K; Wadowsky, R M

    1994-11-01

    The combination of ampicillin and vancomycin kills some but not all strains of ampicillin- and vancomycin-resistant Enterococcus faecium. We compared a simple test for synergy utilizing a commercially available microdilution susceptibility system with time-kill studies and determined acceptable breakpoints for this test for 20 strains of ampicillin- and vancomycin-resistant E. faecium. The combination of ampicillin and vancomycin was tested for synergy by time-kill, broth macrodilution, and broth microdilution procedures. Repeat testing of isolates by macro- and microdilution synergy methods yielded MICs that were within one twofold dilution of each other for both intra- and intertest comparisons. Synergy was always detected by time-kill studies when the MIC of ampicillin in the combination synergy screen was 16 micrograms/ml in the combination microdilution synergy screen. The determination of the synergy by the broth microdilution procedure appears to be simple, convenient, and accurate.

  11. SAR Product Improvements and Enhancements - SARprises

    Science.gov (United States)

    2013-09-30

    paper on current fields at Orkney, Scotland, was accepted for publication in IEEE - TGARS and is currently in press (available on IEEE Xplore as Early...Sea surface velocity vector retrieval using dual-beam interferometry: First demonstration, IEEE TGARS, 43, 2494- 2502, 2005. [2] Chapron, B., F...Bight by airborne along-track interferometric SAR, Proc. IGARSS 2002, 1822-1824, IEEE , 2002. [4] Bjerklie, D.M., S.L. Dingman, C.J. Vorosmarty, C.H

  12. The Radiometric Measurement Quantity for SAR Images

    OpenAIRE

    Döring, Björn J.; Schwerdt, Marco

    2013-01-01

    A Synthetic Aperture Radar (SAR) system measures among other quantities the terrain radar reflectivity. After image calibration, the pixel intensities are commonly expressed in terms of radar cross sections (for point targets) or as backscatter coefficients (for distributed targets), which are directly related. This paper argues that pixel intensities are not generally proportional to radar cross section or derived physical quantities. The paper further proposes to replace the inaccurate term...

  13. Atmospheric Phase Delay in Sentinel SAR Interferometry

    Science.gov (United States)

    Krishnakumar, V.; Monserrat, O.; Crosetto, M.; Crippa, B.

    2018-04-01

    The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR) Interferometry (InSAR) has been a widely used geodetic technique for observing the Earth's surface, especially for mapping the Earth's topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth's atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere) are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC) of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR). To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET) and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC) images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate height and deformation

  14. ATMOSPHERIC PHASE DELAY IN SENTINEL SAR INTERFEROMETRY

    Directory of Open Access Journals (Sweden)

    V. Krishnakumar

    2018-04-01

    Full Text Available The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR Interferometry (InSAR has been a widely used geodetic technique for observing the Earth’s surface, especially for mapping the Earth’s topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth’s atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR. To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate

  15. Multiplier-free filters for wideband SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Christensen, Erik Lintz

    2001-01-01

    This paper derives a set of parameters to be optimized when designing filters for digital demodulation and range prefiltering in SAR systems. Aiming at an implementation in field programmable gate arrays (FPGAs), an approach for the design of multiplier-free filters is outlined. Design results...... are presented in terms of filter complexity and performance. One filter has been coded in VHDL and preliminary results indicate that the filter can meet a 2 GHz input sample rate....

  16. Feature-Based Nonlocal Polarimetric SAR Filtering

    Directory of Open Access Journals (Sweden)

    Xiaoli Xing

    2017-10-01

    Full Text Available Polarimetric synthetic aperture radar (PolSAR images are inherently contaminated by multiplicative speckle noise, which complicates the image interpretation and image analyses. To reduce the speckle effect, several adaptive speckle filters have been developed based on the weighted average of the similarity measures commonly depending on the model or probability distribution, which are often affected by the distribution parameters and modeling texture components. In this paper, a novel filtering method introduces the coefficient of variance ( CV and Pauli basis (PB to measure the similarity, and the two features are combined with the framework of the nonlocal mean filtering. The CV is used to describe the complexity of various scenes and distinguish the scene heterogeneity; moreover, the Pauli basis is able to express the polarimetric information in PolSAR image processing. This proposed filtering combines the CV and Pauli basis to improve the estimation accuracy of the similarity weights. Then, the similarity of the features is deduced according to the test statistic. Subsequently, the filtering is proceeded by using the nonlocal weighted estimation. The performance of the proposed filter is tested with the simulated images and real PolSAR images, which are acquired by AIRSAR system and ESAR system. The qualitative and quantitative experiments indicate the validity of the proposed method by comparing with the widely-used despeckling methods.

  17. The flexion synergy, mother of all synergies and father of new models of gait

    Directory of Open Access Journals (Sweden)

    Jacques eDuysens

    2013-03-01

    Full Text Available Recently there has been a growing interest in the modular organization of leg movements, in particular those related to locomotion. One of the basic modules involves the flexion of the leg during swing and it was shown that this module is already present in neonates (Dominici, et al. 2011. In this paper, we question how these finding build upon the original work by Sherrington, who proposed that the flexor reflex is the basic building block of the flexion during swing phase. Similarly, the relation between the flexor reflex and the withdrawal reflex modules of Schouenborg et al. (1994 will be discussed. It will be argued that there is large overlap between these notions on modules and the older concepts of reflexes. In addition, it will be shown that there is a great flexibility in the expression of some of these modules during gait, thereby allowing for a phase-dependent modulation of the appropriate responses. In particular, the end of the stance phase is a period when the flexor synergy is facilitated. It is proposed that this is linked to the activation of circuitry that is responsible for the generation of locomotor patterns (CPG, central pattern generator. More specifically, it is suggested that the responses in that period relate to the activation of a flexor burst generator. The latter structure forms the core of a new asymmetric model of the CPG. This activation is controlled by afferent input (facilitation by a broad range of afferents, suppression by load afferent input. Meanwhile, many of these physiologic features have found their way in the control of very flexible walking bipedal robots.

  18. Polarimetric SAR image classification based on discriminative dictionary learning model

    Science.gov (United States)

    Sang, Cheng Wei; Sun, Hong

    2018-03-01

    Polarimetric SAR (PolSAR) image classification is one of the important applications of PolSAR remote sensing. It is a difficult high-dimension nonlinear mapping problem, the sparse representations based on learning overcomplete dictionary have shown great potential to solve such problem. The overcomplete dictionary plays an important role in PolSAR image classification, however for PolSAR image complex scenes, features shared by different classes will weaken the discrimination of learned dictionary, so as to degrade classification performance. In this paper, we propose a novel overcomplete dictionary learning model to enhance the discrimination of dictionary. The learned overcomplete dictionary by the proposed model is more discriminative and very suitable for PolSAR classification.

  19. Low-SAR metamaterial-inspired printed monopole antenna

    Science.gov (United States)

    Hossain, M. I.; Faruque, M. R. I.; Islam, M. T.; Ali, M. T.

    2017-01-01

    In this paper, a low-SAR metamaterial-embedded planar monopole antenna is introduced for a wireless communication system. A printed monopole antenna is designed for modern mobile, which operates in GSM, UMTS, LTE, WLAN, and Bluetooth frequency bands. A metamaterial structure is designed to use in the mobile handset with a multi-band printed monopole antenna. The finite integration technique of the CST microwave studio is used in this study. The measurement of antenna performances is taken in an anechoic chamber, and the SAR values are measured using COMOSAR system. The results indicate that metamaterial structure leads to reduce SAR without affecting antenna performance significantly. According to the measured results, the metamaterial attachment leads to reduce 87.7% peak SAR, 68.2% 1-g SAR, and 46.78% 10-g SAR compared to antenna without metamaterial.

  20. Monitoring Building Deformation with InSAR: Experiments and Validation

    Science.gov (United States)

    Yang, Kui; Yan, Li; Huang, Guoman; Chen, Chu; Wu, Zhengpeng

    2016-01-01

    Synthetic Aperture Radar Interferometry (InSAR) techniques are increasingly applied for monitoring land subsidence. The advantages of InSAR include high accuracy and the ability to cover large areas; nevertheless, research validating the use of InSAR on building deformation is limited. In this paper, we test the monitoring capability of the InSAR in experiments using two landmark buildings; the Bohai Building and the China Theater, located in Tianjin, China. They were selected as real examples to compare InSAR and leveling approaches for building deformation. Ten TerraSAR-X images spanning half a year were used in Permanent Scatterer InSAR processing. These extracted InSAR results were processed considering the diversity in both direction and spatial distribution, and were compared with true leveling values in both Ordinary Least Squares (OLS) regression and measurement of error analyses. The detailed experimental results for the Bohai Building and the China Theater showed a high correlation between InSAR results and the leveling values. At the same time, the two Root Mean Square Error (RMSE) indexes had values of approximately 1 mm. These analyses show that a millimeter level of accuracy can be achieved by means of InSAR technique when measuring building deformation. We discuss the differences in accuracy between OLS regression and measurement of error analyses, and compare the accuracy index of leveling in order to propose InSAR accuracy levels appropriate for monitoring buildings deformation. After assessing the advantages and limitations of InSAR techniques in monitoring buildings, further applications are evaluated. PMID:27999403