Science.gov

Sample records for human polyomavirus workshop

  1. The Role of Merkel Cell Polyomavirus and Other Human Polyomaviruses in Emerging Hallmarks of Cancer

    PubMed Central

    Moens, Ugo; Rasheed, Kashif; Abdulsalam, Ibrahim; Sveinbjørnsson, Baldur

    2015-01-01

    Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals, including humans. All polyomaviruses encode the large T-antigen and small t-antigen proteins that share conserved functional domains, comprising binding motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. At present, 13 different human polyomaviruses are known, and for some of them their large T-antigen and small t-antigen have been shown to possess oncogenic properties in cell culture and animal models, while similar functions are assumed for the large T- and small t-antigen of other human polyomaviruses. However, so far the Merkel cell polyomavirus seems to be the only human polyomavirus associated with cancer. The large T- and small t-antigen exert their tumorigenic effects through classical hallmarks of cancer: inhibiting tumor suppressors, activating tumor promoters, preventing apoptosis, inducing angiogenesis and stimulating metastasis. This review elaborates on the putative roles of human polyomaviruses in some of the emerging hallmarks of cancer. The reciprocal interactions between human polyomaviruses and the immune system response are discussed, a plausible role of polyomavirus-encoded and polyomavirus-induced microRNA in cancer is described, and the effect of polyomaviruses on energy homeostasis and exosomes is explored. Therapeutic strategies against these emerging hallmarks of cancer are also suggested. PMID:25866902

  2. Merkel Cell Polyomavirus and Two Novel Polyomaviruses Are Chronically Shed from Human Skin

    PubMed Central

    Schowalter, Rachel M.; Pastrana, Diana V.; Pumphrey, Katherine A.; Moyer, Adam L.; Buck, Christopher B.

    2010-01-01

    Summary Mounting evidence supports the concept that Merkel cell polyomavirus (MCV) is a causal factor underlying most cases of a highly lethal form of skin cancer known as Merkel cell carcinoma. To explore the possibility that polyomaviruses commonly infect healthy human skin, we developed an improved rolling circle amplification (RCA) technique to isolate circular DNA viral genomes from skin swab specimens. Complete MCV genomes were recovered from 14/35 (40%) healthy adults, providing the first full-length, apparently wild-type cloned genomes for this polyomavirus species. RCA analysis also revealed the existence of two previously unknown polyomavirus species that we name human polyomavirus-6 (HPyV6) and HPyV7. Biochemical experiments show that polyomavirus DNA is shed from the skin in the form of assembled virions. A pilot serological study indicates that infection or co-infection with the three skin-tropic polyomaviruses is very common. Thus, at least three polyomavirus species are constituents of the human skin microbiome. PMID:20542254

  3. Survey for human polyomaviruses in cancer

    PubMed Central

    Toptan, Tuna; Yousem, Samuel A.; Ho, Jonhan; Matsushima, Yuki; Stabile, Laura P.; Fernández-Figueras, Maria-Teresa; Bhargava, Rohit; Ryo, Akihide; Moore, Patrick S.; Chang, Yuan

    2016-01-01

    Over the past 8 years, the discovery of 11 new human polyomaviruses (HPyVs) has revived interest in this DNA tumor virus family. Although HPyV infection is widespread and largely asymptomatic, one of these HPyVs, Merkel cell polyomavirus (MCV), is a bona fide human tumor virus. JC virus (JCV), BK virus, HPyV7, and trichodysplasia-spinulosa virus (TSV) can cause nonneoplastic diseases in the setting of immunosuppression. Few specific reagents are available to study the biology of the newly discovered HPyVs. We developed a pan-HPyV-screening method using a cocktail of 3 antibodies that, when combined, recognize T antigen proteins of all HPyVs. We validated detection characteristics of the antibody cocktail by immunoblotting and immunohistochemistry and screened 1,184 cases, including well-defined diseases and tumor tissue microarrays. This assay robustly detected MCV, TSV, JCV, and HPyV7 in etiologically related diseases. We further identified WU polyomavirus in a case of chronic lymphocytic lymphoma-associated bronchitis. Except for scattered, incidentally infected cells in 5% of lung squamous cell carcinomas and colon adenocarcinomas, a broad panel of tumor tissues was largely negative for infection by any HPyV. This method eliminates known HPyVs as suspected causes of cancers investigated in this study. Pan-HPyV survey can be applied to identify diseases associated with recently discovered polyomaviruses. PMID:27034991

  4. Reactivation of human polyomaviruses in immunocompromised states

    PubMed Central

    Wiedinger, Kari; Bitsaktsis, Constantine; Chang, Sulie

    2014-01-01

    Infection with various human polyomaviruses (HPyVs) is prevalent, with rates as high as 80% within the general population. Primary infection occurs during childhood through respiratory or urino-oral transmission. While the majority of individuals exhibit asymptomatic latent infection, those immunocompromised persons are at risk for viral reactivation and disease progression, resulting in conditions such as progressive multifocal leukoencephalopathy (PML), trichodysplasia spinulosa, Merkel cell carcinoma, and polyomavirus associated nephropathy. Individuals with altered immune systems due to HIV, organ transplantation, lymphoproliferative diseases, and monoclonal antibody therapy are particularly susceptible to reactivation of vrarious HPyVs . While the specific factors that induce lytic infection have yet to be defined, it is evident that dysfunctional host cellular immune responses allow active infection to occur. Immunosuppressant conditions, such as in chronic alcohol abuse, may serve as added risk factors for reactivation of HPyVs. Since the human HPyV family is rapidly expanding, continuing studies are needed to characterize the role that known and newly discovered HPyVs play in human disease. PMID:24481784

  5. Human Polyomavirus Reactivation: Disease Pathogenesis and Treatment Approaches

    PubMed Central

    De Gascun, Cillian F.; Carr, Michael J.

    2013-01-01

    JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host. PMID:23737811

  6. Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines.

    PubMed

    Moens, Ugo; Van Ghelue, Marijke; Ludvigsen, Maria; Korup-Schulz, Sarah; Ehlers, Bernhard

    2015-08-01

    Recently, 11 new human polyomaviruses (HPyVs) have been isolated and named KI, WU, Merkel cell polyomavirus (MCPyV), HPyV6,  -7,  -9,  -10 and  -12, Trichodysplasia spinulosa-associated polyomavirus (TSPyV), STLPyV and NJPyV-2013. Little is known about cell tropism of the novel HPyVs, and cell cultures allowing virus propagation are lacking. Because viral tropism partially depends on the interaction of cellular transcription factors with the viral promoter, we monitored the promoter activity of all known HPyVs. Therefore, we compared the relative early and late promoter activity of the BK polyomavirus (BKPyV) (WW strain) with the corresponding activities of the other HPyVs in 10 different cell lines derived from brain, colon, kidney, liver, lung, the oral cavity and skin. Our results show that the BKPyV, MCPyV, TSPyV and HPyV12 early promoters displayed the strongest activity in most cell lines tested, while the remaining HPyV had relative low early promoter activity. HPyV12 showed the highest late promoter activity of all HPyVs in most cell lines, but also the BKPyV, MCPyV and TSPyV late promoters belonged to the stronger ones among HPyVs. The HPyVs with weak early promoter activity had in general also weak late promoter activity, except for HPyV10 whose late promoter was relatively strong in six of the 10 cell lines. A 20 bp deletion in the promoter of an HPyV12 variant significantly affected both early and late promoter activity in most cell lines. In conclusion, our findings suggest which cell lines may be suitable for virus propagation and may give an indication of the cell tropism of the HPyVs.

  7. Detection of Human Polyomavirus 7 in human thymic epithelial tumors

    PubMed Central

    Rennspiess, Dorit; Pujari, Sreedhar; Keijzers, Marlies; Abdul-Hamid, Myrurgia A.; Hochstenbag, Monique; Dingemans, Anne-Marie; Kurz, Anna Kordelia; Speel, Ernst-Jan; Haugg, Anke; Pastrana, Diana V.; Buck, Christopher B.; De Baets, Marc H.; zur Hausen, Axel

    2014-01-01

    Introduction Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Since murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors. Methods HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-PCR and immuno-histochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested. Results HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC large T antigen (LTAg) expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. 40% of the 20 hyperplastic thymi were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative. Conclusions The presence of HPyV7-DNA and LTAg expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG. PMID:25526237

  8. Hamburger polyomaviruses

    PubMed Central

    Peretti, Alberto; FitzGerald, Peter C.; Bliskovsky, Valery

    2015-01-01

    Epidemiological studies have suggested that consumption of beef may correlate with an increased risk of colorectal cancer. One hypothesis to explain this proposed link might be the presence of a carcinogenic infectious agent capable of withstanding cooking. Polyomaviruses are a ubiquitous family of thermostable non-enveloped DNA viruses that are known to be carcinogenic. Using virion enrichment, rolling circle amplification (RCA) and next-generation sequencing, we searched for polyomaviruses in meat samples purchased from several supermarkets. Ground beef samples were found to contain three polyomavirus species. One species, bovine polyomavirus 1 (BoPyV1), was originally discovered as a contaminant in laboratory FCS. A previously unknown species, BoPyV2, occupies the same clade as human Merkel cell polyomavirus and raccoon polyomavirus, both of which are carcinogenic in their native hosts. A third species, BoPyV3, is related to human polyomaviruses 6 and 7. Examples of additional DNA virus families, including herpesviruses, adenoviruses, circoviruses and gyroviruses were also detected either in ground beef samples or in comparison samples of ground pork and ground chicken. The results suggest that the virion enrichment/RCA approach is suitable for random detection of essentially any DNA virus with a detergent-stable capsid. It will be important for future studies to address the possibility that animal viruses commonly found in food might be associated with disease. PMID:25568187

  9. The oncogenic potential of BK-polyomavirus is linked to viral integration into the human genome.

    PubMed

    Kenan, Daniel J; Mieczkowski, Piotr A; Burger-Calderon, Raquel; Singh, Harsharan K; Nickeleit, Volker

    2015-11-01

    It has been suggested that BK-polyomavirus is linked to oncogenesis via high expression levels of large T-antigen in some urothelial neoplasms arising following kidney transplantation. However, a causal association between BK-polyomavirus, large T-antigen expression and oncogenesis has never been demonstrated in humans. Here we describe an investigation using high-throughput sequencing of tumour DNA obtained from an urothelial carcinoma arising in a renal allograft. We show that a novel BK-polyomavirus strain, named CH-1, is integrated into exon 26 of the myosin-binding protein C1 gene (MYBPC1) on chromosome 12 in tumour cells but not in normal renal cells. Integration of the BK-polyomavirus results in a number of discrete alterations in viral gene expression, including: (a) disruption of VP1 protein expression and robust expression of large T-antigen; (b) preclusion of viral replication; and (c) deletions in the non-coding control region (NCCR), with presumed alterations in promoter feedback loops. Viral integration disrupts one MYBPC1 gene copy and likely alters its expression. Circular episomal BK-polyomavirus gene sequences are not found, and the renal allograft shows no productive polyomavirus infection or polyomavirus nephropathy. These findings support the hypothesis that integration of polyomaviruses is essential to tumourigenesis. It is likely that dysregulation of large T-antigen, with persistent over-expression in non-lytic cells, promotes cell growth, genetic instability and neoplastic transformation.

  10. High diversity of human polyomaviruses in environmental and clinical samples in Argentina: Detection of JC, BK, Merkel-cell, Malawi, and human 6 and 7 polyomaviruses.

    PubMed

    Torres, Carolina; Barrios, Melina Elizabeth; Cammarata, Robertina Viviana; Cisterna, Daniel Marcelo; Estrada, Tatiana; Martini Novas, Sergio; Cahn, Pedro; Blanco Fernández, María Dolores; Mbayed, Viviana Andrea

    2016-01-15

    New human polyomaviruses have been recently described. The aim of this work was to detect and characterize human polyomaviruses circulating in Argentina by recovering viruses from environmental and sewage samples and evaluating their potential role as viral indicators of human waste contamination. Analysis was performed in a wider context including viruses from clinical samples from an immunocompromised population. River water and sewage samples were analyzed as a strategy to study the molecular epidemiology of viruses excreted by millions of people. Samples belonged to the Matanza-Riachuelo River (2005-2006: n=25 and 2012: n=20) and sewage from Buenos Aires city and suburbs (2011 and 2013: n=24). Viral detection was performed by PCR and the amplified viral genomes were characterized by phylogenetic analysis. Polyomaviruses were detected in 95.8% of sewage samples, identifying BKPyV (87.5%), JCPyV (83.3%), MCPyV (8.3%) and HPyV6 (8.3%). Besides, one sample collected in 2009 resulted positive for HPyV7. In 2005-2006, polyomaviruses were detected in 84.0% of river water samples, with the highest detection for MCPyV (52.0%), followed by BKPyV (44.0%), JCPyV (20.0%) and MWPyV (4.0%). In 2012, polyomaviruses were detected in 85.0% of river samples, finding JCPyV (85.0%), BKPyV (75.0%), MCPyV (25.0%) and HPyV6 (25.0%). Also, polyomaviruses, including JCPyV, BKPyV and MCPyV, were detected in 63.2% of urine samples from patients infected with HIV (n=19). Characterization indicated the coexistence of different genotypes and variants for each virus, particularly in sewage. MCPyV sequences (the only sequences from Argentina) formed a monophyletic group with the single sequence available for South America (French Guiana). The high level of detection and viral diversity found by environmental surveillance, which involved the characterization of viruses not previously described in South America, reinforces the usefulness of this approach to monitor viral contamination and

  11. High diversity of human polyomaviruses in environmental and clinical samples in Argentina: Detection of JC, BK, Merkel-cell, Malawi, and human 6 and 7 polyomaviruses.

    PubMed

    Torres, Carolina; Barrios, Melina Elizabeth; Cammarata, Robertina Viviana; Cisterna, Daniel Marcelo; Estrada, Tatiana; Martini Novas, Sergio; Cahn, Pedro; Blanco Fernández, María Dolores; Mbayed, Viviana Andrea

    2016-01-15

    New human polyomaviruses have been recently described. The aim of this work was to detect and characterize human polyomaviruses circulating in Argentina by recovering viruses from environmental and sewage samples and evaluating their potential role as viral indicators of human waste contamination. Analysis was performed in a wider context including viruses from clinical samples from an immunocompromised population. River water and sewage samples were analyzed as a strategy to study the molecular epidemiology of viruses excreted by millions of people. Samples belonged to the Matanza-Riachuelo River (2005-2006: n=25 and 2012: n=20) and sewage from Buenos Aires city and suburbs (2011 and 2013: n=24). Viral detection was performed by PCR and the amplified viral genomes were characterized by phylogenetic analysis. Polyomaviruses were detected in 95.8% of sewage samples, identifying BKPyV (87.5%), JCPyV (83.3%), MCPyV (8.3%) and HPyV6 (8.3%). Besides, one sample collected in 2009 resulted positive for HPyV7. In 2005-2006, polyomaviruses were detected in 84.0% of river water samples, with the highest detection for MCPyV (52.0%), followed by BKPyV (44.0%), JCPyV (20.0%) and MWPyV (4.0%). In 2012, polyomaviruses were detected in 85.0% of river samples, finding JCPyV (85.0%), BKPyV (75.0%), MCPyV (25.0%) and HPyV6 (25.0%). Also, polyomaviruses, including JCPyV, BKPyV and MCPyV, were detected in 63.2% of urine samples from patients infected with HIV (n=19). Characterization indicated the coexistence of different genotypes and variants for each virus, particularly in sewage. MCPyV sequences (the only sequences from Argentina) formed a monophyletic group with the single sequence available for South America (French Guiana). The high level of detection and viral diversity found by environmental surveillance, which involved the characterization of viruses not previously described in South America, reinforces the usefulness of this approach to monitor viral contamination and

  12. In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

    PubMed Central

    Barth, Heidi; Solis, Morgane; Kack-Kack, Wallys; Soulier, Eric; Velay, Aurélie; Fafi-Kremer, Samira

    2016-01-01

    Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned. PMID:27782080

  13. First Detection of Human Papillomaviruses and Human Polyomaviruses in River Waters in Italy.

    PubMed

    Iaconelli, M; Petricca, S; Libera, S Della; Di Bonito, P; La Rosa, G

    2015-12-01

    Waterborne exposure to human viruses is possible through contact with contaminated water environments and can result in infections associated with a wide range of illnesses, including gastrointestinal, respiratory, ear, ocular, and skin infections. Recently, the occurrence in water environments of two groups of human viruses-both known with oncogenic potential, human polyomaviruses (HPyVs) and papillomaviruses (HPVs)-has been reported worldwide. These viruses, responsible for highly prevalent infections worldwide, have recently been proposed as potentially emerging waterborne pathogens. The objective of the present study was to examine the occurrence of HPyVs and HPVs in surface waters, by monitoring two rivers in Northwestern Italy, by nested PCR assays and sequencing. HPyVs (JC, BK, and Merkel cell polyomavirus) were detected in 10/25 (40%) samples. HPVs (HPV8, 17, 21, 25, 32, 80, 99, 105, and putative new HPVs) were identified in 14/25 (56%) river samples. The number of HPV DNA copies in waters was measured by quantitative real-time PCR. To our knowledge, this is the first detection and quantification of HPVs in surface waters. The possibility that HPyVs and HPVs can be transmitted by the waterborne route deserves to be explored in future studies. PMID:26049729

  14. First Detection of Human Papillomaviruses and Human Polyomaviruses in River Waters in Italy.

    PubMed

    Iaconelli, M; Petricca, S; Libera, S Della; Di Bonito, P; La Rosa, G

    2015-12-01

    Waterborne exposure to human viruses is possible through contact with contaminated water environments and can result in infections associated with a wide range of illnesses, including gastrointestinal, respiratory, ear, ocular, and skin infections. Recently, the occurrence in water environments of two groups of human viruses-both known with oncogenic potential, human polyomaviruses (HPyVs) and papillomaviruses (HPVs)-has been reported worldwide. These viruses, responsible for highly prevalent infections worldwide, have recently been proposed as potentially emerging waterborne pathogens. The objective of the present study was to examine the occurrence of HPyVs and HPVs in surface waters, by monitoring two rivers in Northwestern Italy, by nested PCR assays and sequencing. HPyVs (JC, BK, and Merkel cell polyomavirus) were detected in 10/25 (40%) samples. HPVs (HPV8, 17, 21, 25, 32, 80, 99, 105, and putative new HPVs) were identified in 14/25 (56%) river samples. The number of HPV DNA copies in waters was measured by quantitative real-time PCR. To our knowledge, this is the first detection and quantification of HPVs in surface waters. The possibility that HPyVs and HPVs can be transmitted by the waterborne route deserves to be explored in future studies.

  15. Human BK Polyomavirus-The Potential for Head and Neck Malignancy and Disease.

    PubMed

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-07-08

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

  16. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    PubMed Central

    Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian

    2014-01-01

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC. PMID:24978434

  17. Comparative Inactivation of Murine Norovirus, Human Adenovirus, and Human JC Polyomavirus by Chlorine in Seawater

    PubMed Central

    de Abreu Corrêa, Adriana; Carratala, Anna; Barardi, Celia Regina Monte; Calvo, Miquel; Bofill-Mas, Sílvia

    2012-01-01

    Viruses excreted by humans affect the commercial and recreational use of coastal water. Shellfish produced in contaminated waters have been linked to many episodes and outbreaks of viral gastroenteritis, as well as other food-borne diseases worldwide. The risk can be reduced by appropriate treatment following harvesting and by depuration. The kinetics of inactivation of murine norovirus 1 and human adenovirus 2 in natural and artificial seawater by free available chlorine was studied by quantifying genomic copies (GC) using quantitative PCR and infectious viral particles (PFU). Human JC polyomavirus Mad4 kinetics were evaluated by quantitative PCR. DNase or RNase were used to eliminate free genomes and assess potential viral infectivity when molecular detection was performed. At 30 min of assay, human adenovirus 2 showed 2.6- and 2.7-log10 GC reductions and a 2.3- and 2.4-log10 PFU reductions in natural and artificial seawater, respectively, and infectious viral particles were still observed at the end of the assay. When DNase was used prior to the nucleic acid extraction the kinetic of inactivation obtained by quantitative PCR was statistically equivalent to the one observed by infectivity assays. For murine norovirus 1, 2.5, and 3.5-log10 GC reductions were observed in natural and artificial seawater, respectively, while no viruses remained infectious after 30 min of contact with chlorine. Regarding JC polyomavirus Mad4, 1.5- and 1.1-log10 GC reductions were observed after 30 min of contact time. No infectivity assays were conducted for this virus. The results obtained provide data that might be applicable to seawater used in shellfish depuration. PMID:22773637

  18. Genome Sequence of a Central Chimpanzee-Associated Polyomavirus Related to BK and JC Polyomaviruses, Pan troglodytes troglodytes Polyomavirus 1.

    PubMed

    Madinda, Nadège F; Robbins, Martha M; Boesch, Christophe; Leendertz, Fabian H; Ehlers, Bernhard; Calvignac-Spencer, Sébastien

    2015-09-03

    We amplified and sequenced the genome of a polyomavirus infecting a central chimpanzee (Pan troglodytes troglodytes). This virus, which is closely related to BK and JC polyomaviruses, may help shed a new light on these human pathogens' evolutionary history.

  19. Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus.

    PubMed

    Haley, Sheila A; O'Hara, Bethany A; Nelson, Christian D S; Brittingham, Frances L P; Henriksen, Kammi J; Stopa, Edward G; Atwood, Walter J

    2015-08-01

    The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal α2,6-linked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. PMID:26056932

  20. Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

    PubMed Central

    Haley, Sheila A.; O'Hara, Bethany A.; Nelson, Christian D.S.; Brittingham, Frances L.P.; Henriksen, Kammi J.; Stopa, Edward G.; Atwood, Walter J.

    2016-01-01

    The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal α2,6–linked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. PMID:26056932

  1. Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells.

    PubMed

    Tylden, Garth D; Hirsch, Hans H; Rinaldo, Christine Hanssen

    2015-01-01

    BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 to 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV; previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary human renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 h reduced icBKPyV similarly to treatment from 2 to 72 h postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC viability, mean selectivity indices at 50 and 90% inhibition (SI50 and SI90) calculated for cellular DNA replication were 2.7 and 2.9, respectively, those for mitochondrial activity were 8.9 and 10.4, those for total ATP were 8.6 and 8.2, and those for membrane integrity were 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations of ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results.

  2. Polyomaviruses of Nonhuman Primates: Implications for Research

    PubMed Central

    Simon, Meredith A

    2008-01-01

    Polyomaviruses are a family of small nonenveloped DNA viruses that infect birds and mammals. At least 7 nonhuman primate polyomaviruses that occur in macaques, African green monkeys, marmosets baboons, and chimpanzees have been described, as well as 4 polyomaviruses that occur in humans. Simian virus 40 (SV40), which infects macaques, was the first nonhuman primate polyomavirus identified as a contaminant of early polio vaccines. Primate polyomaviruses cause inapparent primary infections but persist in the host and can cause severe disease in situations of immunocompromise. This review describes the primate polyomaviruses, and the diseases associated with the viruses of macaques. In macaques, the greatest current concerns are the potential confounding of study results by polyomavirus infections and the zoonotic potential of SV40. PMID:19793457

  3. Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) in non small cell lung cancer.

    PubMed

    Joh, Joongho; Jenson, A Bennett; Moore, Grace D; Rezazedeh, Arash; Slone, Stephen P; Ghim, Shin-je; Kloecker, Goetz H

    2010-12-01

    Certain types of human papillomavirus (HPV) induce cancers, especially cervical cancers in women. A meta-analysis of the literature suggests that HPV is also associated with 20%-25% of non small cell lung carcinoma (NSCLC). Merkel cell Polyomavirus (MCPyV) causes most Merkel cell carcinomas in immunocompromised hosts, and is associated with some squamous carcinomas of skin in immunocompetent individuals. Since both oncogenic viruses appear to involve the tonsils and, therefore, have clear access to the lungs, we examined that the possible association of HPV and MCPyV infections with lung cancers, especially, NSCLC. DNAs were extracted from 51 frozen tissues from 30 lung cancer patients, and examined for the presence of HPV and MCPyV by PCR and DNA sequencing analysis. Clinical data was correlated with the viral status. HPVs were only detected in 5 adenocarcinomas (16.7% of all lung cancers examined). Three were positive for HPV-16, 1 for HPV-11 and 1 had an unknown HPV type DNA. None was identified in benign tissue. MCPyV DNA was detected in 5 NSCLCs (16.7%). Three of the 5 were identified in squamous carcinomas, 1 in adenocarcinoma, and 1 in an unspecified NSCLC. Two additional samples were positive for MCPyV DNA within benign adjacent lung tissue only. In one adenocarcinoma, HPV-11 was identified in an adenocarcinoma, and MCPyV DNA was detected in the adjacent "benign" tissue. HPV and MCPyV were directly associated with 33.3% of NSCLC. Further studies are necessary to determine if polyomavirus and papillomavirus are necessary risk factors for some cases of NSCLC.

  4. Molecular characterization of the first polyomavirus from a New World primate: squirrel monkey polyomavirus.

    PubMed

    Verschoor, Ernst J; Groenewoud, Marlous J; Fagrouch, Zahra; Kewalapat, Aruna; van Gessel, Sabine; Kik, Marja J L; Heeney, Jonathan L

    2008-01-01

    DNA samples from a variety of New World monkeys were screened by using a broad-spectrum PCR targeting the VP1 gene of polyomaviruses. This resulted in the characterization of the first polyomavirus from a New World primate. This virus naturally infects squirrel monkeys (Saimiri sp.) and is provisionally named squirrel monkey polyomavirus (SquiPyV). The complete genome of SquiPyV is 5,075 bp in length, and encodes the small T and large T antigens and the three structural proteins VP1, VP2 and VP3. Interestingly, the late region also encodes a putative agnoprotein, a feature that it shares with other polyomaviruses from humans, baboons and African green monkeys. Comparison with other polyomaviruses revealed limited sequence similarity to any other polyomavirus, and phylogenetic analysis of the VP1 gene confirmed its uniqueness.

  5. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    PubMed Central

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens; Albrecht, Eva; Gieger, Christian; Khademi, Mohsen; Lima Bomfim, Izaura; Fogdell-Hahn, Anna; Link, Jenny; Alfredsson, Lars; Søndergaard, Helle Bach; Hillert, Jan; Oturai, Annette B.; Hemme, Bernhard

    2014-01-01

    JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50–60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10−15) and controls (OR = 0.53, p = 2×10−5). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10−5). The German dataset confirmed these findings (OR = 0.54, p = 1×10−4 and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays

  6. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    PubMed

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens; Albrecht, Eva; Gieger, Christian; Khademi, Mohsen; Lima Bomfim, Izaura; Fogdell-Hahn, Anna; Link, Jenny; Alfredsson, Lars; Søndergaard, Helle Bach; Hillert, Jan; Oturai, Annette B; Hemmer, Bernhard; Hemme, Bernhard; Kockum, Ingrid; Olsson, Tomas

    2014-04-01

    JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10(-5)). The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4) and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the

  7. Complete Genome Sequence of a Novel Human WU Polyomavirus Isolate Associated with Acute Respiratory Infection

    PubMed Central

    Dehority, Walter N.; Schwalm, Kurt C.; Young, Jesse M.; Gross, Stephen M.; Schroth, Gary P.; Young, Stephen A.

    2016-01-01

    We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, NM040708, collected from a patient with an acute respiratory infection in New Mexico. The double-stranded DNA (dsDNA) genome of NM040708 is 5,229 bp in length and differs from the WUPyV reference with accession no. NC_009539 by 6 nucleotides and 2 amino acids. PMID:27151782

  8. Detection of Human-Derived Fecal Pollution in Environmental Waters by Use of a PCR-Based Human Polyomavirus Assay▿

    PubMed Central

    McQuaig, Shannon M.; Scott, Troy M.; Harwood, Valerie J.; Farrah, Samuel R.; Lukasik, Jerzy O.

    2006-01-01

    Regulatory agencies mandate the use of fecal coliforms, Escherichia coli or Enterococcus spp., as microbial indicators of recreational water quality. These indicators of fecal pollution do not identify the specific sources of pollution and at times underestimate health risks associated with recreational water use. This study proposes the use of human polyomaviruses (HPyVs), which are widespread among human populations, as indicators of human fecal pollution. A method was developed to concentrate and extract HPyV DNA from environmental water samples and then to amplify it by nested PCR. HPyVs were detected in as little as 1 μl of sewage and were not amplified from dairy cow or pig wastes. Environmental water samples were screened for the presence of HPyVs and two additional markers of human fecal pollution: the Enterococcus faecium esp gene and the 16S rRNA gene of human-associated Bacteroides. The presence of human-specific indicators of fecal pollution was compared to fecal coliform and Enterococcus concentrations. HPyVs were detected in 19 of 20 (95%) samples containing the E. faecium esp gene and Bacteroides human markers. Weak or no correlation was observed between the presence/absence of human-associated indicators and counts of indicator bacteria. The sensitivity, specificity, and correlation with other human-associated markers suggest that the HPyV assay could be a useful predictor of human fecal pollution in environmental waters and an important component of the microbial-source-tracking “toolbox.” PMID:16997988

  9. Distribution of human polyomaviruses, adenoviruses, and hepatitis E virus in the environment and in a drinking-water treatment plant.

    PubMed

    Albinana-Gimenez, Nestor; Clemente-Casares, Pilar; Bofill-Mas, Silvia; Hundesa, Ayalkibet; Ribas, Ferran; Girones, Rosina

    2006-12-01

    Large numbers of viruses are excreted in human feces and urine, which even at low concentrations may cause illness when ingested. Some of these viruses have not been traditionally monitored in terms of waterborne diseases and are considered emergent viruses, such as hepatitis E virus (HEV) and JC and BK polyomavirus (JCPyV and BKPyV). The high prevalence of human adenoviruses (HAdV) and polyomaviruses, which both show DNA genomes, in sewage from widely divergent areas has suggested the relevance of evaluating these viruses as possible indicators of viral contamination. The concentration of these viruses was analyzed in sewage and river water and after treatment in a drinking-water treatment plant including chlorination, flocculation, ozonation, and granulate active carbon (GAC) filtration. Samples of GAC-filtered water were collected before a second chlorination treatment. The river used as a source of fresh water presented an average concentration of 2.6 x 10(1) JCPyV and 4 x 10(2) HAdV GC (genome copies)/L. A removal of 2 logarithms (99%) of HAdV and JCPyV was observed in the drinking-water treatment plant. All the GAC-filtered water samples studied contained HAdV, with a mean value of 4.3 HAdV GC/L. HEV strains belonging to genotype 3 were frequently detected in low concentrations in urban sewage and in biosolids or sewage containing swine feces but not in the river water samples studied. The detection of viruses by molecular techniques is useful for genetically describe emergent viruses in community wastewaters and water supplies. Quantification of JCPyV and HAdV using quantitative real-time PCR (QPCR) may be useful for evaluating virus removal efficiency in water treatment plants and as an index of the virological quality of water and of the potential presence of human viruses.

  10. JC Polyomavirus Infection of Primary Human Renal Epithelial Cells Is Controlled by a Type I IFN-Induced Response

    PubMed Central

    Assetta, Benedetta; De Cecco, Marco; O’Hara, Bethany

    2016-01-01

    ABSTRACT The JC and BK human polyomaviruses (JCPyV and BKPyV, respectively) establish lifelong persistent infections in the kidney. In immunosuppressed individuals, JCPyV causes progressive multifocal leukoencephalopathy (PML), a fatal neurodegenerative disease, and BKPyV causes polyomavirus-associated nephropathy (PVN). In this study, we compared JCPyV and BKPyV infections in primary human renal proximal tubule epithelial (HRPTE) cells. JCPyV established a persistent infection, but BKPyV killed the cells in 15 days. To identify the cellular factors responsible for controlling JCPyV infection and promoting viral persistence, we profiled the transcriptomes of JCPyV- and BKPyV-infected cells at several time points postinfection. We found that infection with both viruses induced interferon production but that interferon-stimulated genes (ISGs) were only activated in the JCPyV-infected cells. Phosphorylated STAT1 and IRF9, which are responsible for inducing ISGs, translocated to the nucleus of JCPyV-infected cells but did not in BKPyV-infected cells. In BKPyV-infected cells, two critical suppressors of cytokine signaling, SOCS3 and SOCS1, were induced. Infection with BKPyV but not JCPyV caused reorganization of PML bodies that are associated with inactivating antiviral responses. Blockade of the interferon receptor and neutralization of soluble interferon alpha (IFN-α) and IFN-β partially alleviated the block to JCPyV infection, leading to enhanced infectivity. Our results show that a type I IFN response contributes to the establishment of persistent infection by JCPyV in HRPTE cells. PMID:27381292

  11. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

    PubMed

    Rinaldo, Christine Hanssen; Gosert, Rainer; Bernhoff, Eva; Finstad, Solrun; Hirsch, Hans H

    2010-11-01

    Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC(90)) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC(90)s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells in vitro.

  12. Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy.

    PubMed

    Jelcic, Ivan; Combaluzier, Benoit; Jelcic, Ilijas; Faigle, Wolfgang; Senn, Luzia; Reinhart, Brenda J; Ströh, Luisa; Nitsch, Roger M; Stehle, Thilo; Sospedra, Mireia; Grimm, Jan; Martin, Roland

    2015-09-23

    In immunocompromised individuals, JC polyomavirus (JCPyV) may mutate and gain access to the central nervous system resulting in progressive multifocal leukoencephalopathy (PML), an often fatal opportunistic infection for which no treatments are currently available. Despite recent progress, the contribution of JCPyV-specific humoral immunity to controlling asymptomatic infection throughout life and to eliminating JCPyV from the brain is poorly understood. We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti-VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show "recognition holes"; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell repertoire of individuals who recovered from PML could be a source for the molecular cloning of broadly neutralizing antibodies for passive immunization. We generated a series of memory B cell-derived JCPyV VP1-specific human monoclonal antibodies from HDs and a patient with NAT-associated PML-immune reconstitution inflammatory syndrome (IRIS). These antibodies exhibited diverse binding affinity, cross-reactivity with the closely related BK polyomavirus, recognition of PML-causing VP1 variants, and JCPyV neutralization. Almost all antibodies with exquisite specificity for JCPyV, neutralizing activity, recognition of all tested JCPyV PML variants, and high affinity were derived from one patient who had recovered from PML. These antibodies are promising drug candidates for the development of a treatment of PML. PMID:26400911

  13. Human Genome Diversity workshop 1

    SciTech Connect

    1992-12-31

    The Human Genome Diversity Project (HGD) is an international interdisciplinary program whose goal is to reveal as much as possible about the current state of genetic diversity among humans and the processes that were responsible for that diversity. Classical premolecular techniques have already proved that a significant component of human genetic variability lies within populations rather than among them. New molecular techniques will permit a dramatic increase in the resolving power of genetic analysis at the population level. Recent social changes in many parts of the world threaten the identity of a number of populations that may be extremely important for understanding human evolutionary history. It is therefore urgent to conduct research on human variation in these areas, while there is still time. The plan is to identify the most representative descendants of ancestral human populations worldwide and then to preserve genetic records of these populations. This is a report of the Population Genetics Workshop (Workshop 1), the first of three to be held to plan HGD, which was focused on sampling strategies and analytic methods from population genetics. The topics discussed were sampling and population structure; analysis of populations; drift versus natural selection; modeling migration and population subdivision; and population structure and subdivision.

  14. Human Reliability Program Workshop

    SciTech Connect

    Landers, John; Rogers, Erin; Gerke, Gretchen

    2014-05-18

    A Human Reliability Program (HRP) is designed to protect national security as well as worker and public safety by continuously evaluating the reliability of those who have access to sensitive materials, facilities, and programs. Some elements of a site HRP include systematic (1) supervisory reviews, (2) medical and psychological assessments, (3) management evaluations, (4) personnel security reviews, and (4) training of HRP staff and critical positions. Over the years of implementing an HRP, the Department of Energy (DOE) has faced various challenges and overcome obstacles. During this 4-day activity, participants will examine programs that mitigate threats to nuclear security and the insider threat to include HRP, Nuclear Security Culture (NSC) Enhancement, and Employee Assistance Programs. The focus will be to develop an understanding of the need for a systematic HRP and to discuss challenges and best practices associated with mitigating the insider threat.

  15. Novel polyomavirus detected in the feces of a chimpanzee by nested broad-spectrum PCR.

    PubMed

    Johne, Reimar; Enderlein, Dirk; Nieper, Hermann; Müller, Hermann

    2005-03-01

    In order to screen for new polyomaviruses in samples derived from various animal species, degenerated PCR primer pairs were constructed. By using a nested PCR protocol, the sensitive detection of nine different polyomavirus genomes was demonstrated. The screening of field samples revealed the presence of a new polyomavirus, tentatively designated chimpanzee polyomavirus (ChPyV), in the feces of a juvenile chimpanzee (Pan troglodytes). Analysis of the region encoding the major capsid protein VP1 revealed a unique insertion in the EF loop of the protein and showed that ChPyV is a distinct virus related to the monkey polyomavirus B-lymphotropic polyomavirus and the human polyomavirus JC polyomavirus. PMID:15731285

  16. Novel Polyomavirus Detected in the Feces of a Chimpanzee by Nested Broad-Spectrum PCR

    PubMed Central

    Johne, Reimar; Enderlein, Dirk; Nieper, Hermann; Müller, Hermann

    2005-01-01

    In order to screen for new polyomaviruses in samples derived from various animal species, degenerated PCR primer pairs were constructed. By using a nested PCR protocol, the sensitive detection of nine different polyomavirus genomes was demonstrated. The screening of field samples revealed the presence of a new polyomavirus, tentatively designated chimpanzee polyomavirus (ChPyV), in the feces of a juvenile chimpanzee (Pan troglodytes). Analysis of the region encoding the major capsid protein VP1 revealed a unique insertion in the EF loop of the protein and showed that ChPyV is a distinct virus related to the monkey polyomavirus B-lymphotropic polyomavirus and the human polyomavirus JC polyomavirus. PMID:15731285

  17. Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under natalizumab treatment.

    PubMed

    Pietropaolo, Valeria; Bellizzi, Anna; Anzivino, Elena; Iannetta, Marco; Zingaropoli, Maria Antonella; Rodio, Donatella Maria; Morreale, Manuela; Pontecorvo, Simona; Francia, Ada; Vullo, Vincenzo; Palamara, Anna Teresa; Ciardi, Maria Rosa

    2015-12-01

    In the last years, the treatment of multiple sclerosis (MS) patients with natalizumab has been associated with the occurrence of progressive multifocal leukoencephalopathy (PML) caused by human polyomavirus JC (JCV). Here, we have shown a significant correlation between patients with JC viruria and positive JC-specific antibody response and patients without JCV-specific antibodies after 1 year of natalizumab (p = 0.0006). Furthermore, JCV-specific quantitative PCR on urine and plasma samples, collected at the enrollment (t0) and every 4 months (t1, t2, t3) in the first year and at two time points (t4 and t5) in the second year of natalizumab treatment, indicated the prevalence of JC viremia rather than JC viruria only in the second year of treatment (p = 0.04). Moreover, the analysis of JCV non-coding control region (NCCR) sequences in peripheral blood mononuclear cells of patients with JC-specific antibodies after 12 natalizumab infusions (t3) revealed the presence of rearranged sequences, whereas the prevalence of genotypes 1A, 1B, and 4 was detected in these patients by VP1 sequence analysis. In summary, JC viruria evaluation seems to be useful to identify early those patients who do not already develop a humoral immune response against JCV. It may also be interesting to study the JCV NCCR rearrangements since they could give us new insights on the onset of neuro-invasive viral variants. PMID:25930159

  18. Crystallographic and Glycan Microarray Analysis of Human Polyomavirus 9 VP1 Identifies N-Glycolyl Neuraminic Acid as a Receptor Candidate

    PubMed Central

    Khan, Zaigham Mahmood; Liu, Yan; Neu, Ursula; Gilbert, Michel; Ehlers, Bernhard

    2014-01-01

    ABSTRACT Human polyomavirus 9 (HPyV9) is a closely related homologue of simian B-lymphotropic polyomavirus (LPyV). In order to define the architecture and receptor binding properties of HPyV9, we solved high-resolution crystal structures of its major capsid protein, VP1, in complex with three putative oligosaccharide receptors identified by glycan microarray screening. Comparison of the properties of HPyV9 VP1 with the known structure and glycan-binding properties of LPyV VP1 revealed that both viruses engage short sialylated oligosaccharides, but small yet important differences in specificity were detected. Surprisingly, HPyV9 VP1 preferentially binds sialyllactosamine compounds terminating in 5-N-glycolyl neuraminic acid (Neu5Gc) over those terminating in 5-N-acetyl neuraminic acid (Neu5Ac), whereas LPyV does not exhibit such a preference. The structural analysis demonstrated that HPyV9 makes specific contacts, via hydrogen bonds, with the extra hydroxyl group present in Neu5Gc. An equivalent hydrogen bond cannot be formed by LPyV VP1. IMPORTANCE The most common sialic acid in humans is 5-N-acetyl neuraminic acid (Neu5Ac), but various modifications give rise to more than 50 different sialic acid variants that decorate the cell surface. Unlike most mammals, humans cannot synthesize the sialic acid variant 5-N-glycolyl neuraminic acid (Neu5Gc) due to a gene defect. Humans can, however, still acquire this compound from dietary sources. The role of Neu5Gc in receptor engagement and in defining viral tropism is only beginning to emerge, and structural analyses defining the differences in specificity for Neu5Ac and Neu5Gc are still rare. Using glycan microarray screening and high-resolution protein crystallography, we have examined the receptor specificity of a recently discovered human polyomavirus, HPyV9, and compared it to that of the closely related simian polyomavirus LPyV. Our study highlights critical differences in the specificities of both viruses

  19. Polycyclic aromatic hydrocarbons-induced ROS accumulation enhances mutagenic potential of T-antigen from human polyomavirus JC.

    PubMed

    Wilk, Anna; Waligórski, Piotr; Lassak, Adam; Vashistha, Himanshu; Lirette, David; Tate, David; Zea, Arnold H; Koochekpour, Shahriar; Rodriguez, Paulo; Meggs, Leonard G; Estrada, John J; Ochoa, Augusto; Reiss, Krzysztof

    2013-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are the products of incomplete combustion of organic materials, which are present in cigarette smoke, deep-fried food, and in natural crude oil. Since PAH-metabolites form DNA adducts and cause oxidative DNA damage, we asked if these environmental carcinogens could affect transforming potential of the human Polyomavirus JC oncoprotein, T-antigen (JCV T-antigen). We extracted DMSO soluble PAHs from Deepwater Horizon oil spill in the Gulf of Mexico (oil-PAHs), and detected several carcinogenic PAHs. The oil-PAHs were tested in exponentially growing cultures of normal mouse fibroblasts (R508), and in R508 stably expressing JCV T-antigen (R508/T). The oil-PAHs were cytotoxic only at relatively high doses (1:50-1:100 dilution), and at 1:500 dilution the growth and cell survival rates were practically unaffected. This non-toxic dose triggered however, a significant accumulation of reactive oxygen species (ROS), caused oxidative DNA damage and the formation of DNA double strand breaks (DSBs). Although oil-PAHs induced similar levels of DNA damage in R508 and R508/T cells, only T-antigen expressing cells demonstrated inhibition of high fidelity DNA repair by homologous recombination (HRR). In contrast, low-fidelity repair by non-homologous end joining (NHEJ) was unaffected. This potential mutagenic shift between DNA repair mechanisms was accompanied by a significant increase in clonal growth of R508/T cells chronically exposed to low doses of the oil-PAHs. Our results indicate for the first time carcinogenic synergy in which oil-PAHs trigger oxidative DNA damage and JCV T-antigen compromises DNA repair fidelity. PMID:23558788

  20. BK polyomavirus: emerging pathogen.

    PubMed

    Bennett, Shauna M; Broekema, Nicole M; Imperiale, Michael J

    2012-08-01

    BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols. PMID:22402031

  1. New Insights on Human Polyomavirus JC and Pathogenesis of Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Bellizzi, Anna; Anzivino, Elena; Rodio, Donatella Maria; Palamara, Anna Teresa; Nencioni, Lucia; Pietropaolo, Valeria

    2013-01-01

    John Cunningham virus (JCV) is a member of the Polyomaviridae family. It was first isolated from the brain of a patient with Hodgkin disease in 1971, and since then the etiological agent of the progressive multifocal leukoencephalopathy (PML) was considered. Until the human immunodeficiency virus (HIV) pandemic, PML was rare: in fact HIV-induced immunodeficiency is the most common predisposing factor accounting for 85% of all instances of PML. This data led to intense research on JCV infection and resulted in better understanding of epidemiology and clinic-pathologic spectrum. Recently, cases of PML have been observed after the introduction of monoclonal antibodies, such as natalizumab, rituximab, efalizumab, and infliximab, in the treatment of autoimmune disease, underlining the important role of host immunity in PML pathogenesis. In this review current understanding of the JCV infection and the new findings relating to the pathogenesis of PML has been comprehensively revised, focusing our attention on the interaction between the cellular and viral molecular pathways implicated in the JCV infection and the modulating role of host immune surveillance in the viral reactivation from a latent state. PMID:23690827

  2. Complete Sequence of the Smallest Polyomavirus Genome, Giant Guitarfish (Rhynchobatus djiddensis) Polyomavirus 1.

    PubMed

    Dill, Jennifer A; Ng, Terry F F; Camus, Alvin C

    2016-01-01

    Polyomaviruses are known to infect mammals and birds. Deep sequencing and metagenomic analysis identified the first polyomavirus from a cartilaginous fish, the giant guitarfish (Rhynchobatus djiddensis). Giant guitarfish polyomavirus 1 (GfPyV1) has typical polyomavirus genome organization, but is the smallest polyomavirus genome (3.96 kb) described to date. PMID:27198025

  3. Complete Sequence of the Smallest Polyomavirus Genome, Giant Guitarfish (Rhynchobatus djiddensis) Polyomavirus 1

    PubMed Central

    Dill, Jennifer A.

    2016-01-01

    Polyomaviruses are known to infect mammals and birds. Deep sequencing and metagenomic analysis identified the first polyomavirus from a cartilaginous fish, the giant guitarfish (Rhynchobatus djiddensis). Giant guitarfish polyomavirus 1 (GfPyV1) has typical polyomavirus genome organization, but is the smallest polyomavirus genome (3.96 kb) described to date. PMID:27198025

  4. Natural History of Polyomaviruses in Men: The HPV Infection in Men (HIM) Study

    PubMed Central

    Hampras, Shalaka S.; Giuliano, Anna R.; Lin, Hui-Yi; Fisher, Kate J.; Abrahamsen, Martha E.; McKay-Chopin, Sandrine; Gheit, Tarik; Tommasino, Massimo; Rollison, Dana E.

    2015-01-01

    Background. Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa–associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study. Methods. Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction. Results. MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03–4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01–6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively. Conclusion. MCPyV infection is highly prevalent in adults, with age and race being predisposing factors. PMID:25387582

  5. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

    PubMed Central

    Siebrasse, Erica A.; Nguyen, Nang L.; Willby, Melisa J.; Erdman, Dean D.; Menegus, Marilyn A.

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. PMID:26691850

  6. Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: preliminary results.

    PubMed

    Nardis, Chiara; Anzivino, Elena; Bellizzi, Anna; Rodio, Donatella M; De Pità, Ornella; Chiarini, Fernanda; Pietropaolo, Valeria

    2012-12-01

    Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter-related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life-threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real-time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non-coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non-pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow-up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise. PMID:22422468

  7. ENVIRONMENTAL-HUMAN HEALTH INTERCONNECTIONS: A WORKSHOP REPORT

    EPA Science Inventory

    A Pellston Workshop jointly sponsored by SETAC and SOT to discuss this topic of "Interconnections" was held in June, 2000 in Snowbird, Utah. This workshop was motivated by a deep concern shared by many human health, environmental, and social scientists for the interconnections, ...

  8. Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran.

    PubMed

    Yahyapour, Yousef; Sadeghi, Farzin; Alizadeh, Ahad; Rajabnia, Ramazan; Siadati, Sepideh

    2016-10-01

    Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 non-cancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and non-cancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non-cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 × 10(-5) ± 2.4 × 10(-5) and 6.0 × 10(-6) ± 1.3 × 10(-5) per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01-6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.

  9. Epidemiologic studies of polyomaviruses and cancer: previous findings, methodologic challenges and future directions.

    PubMed

    Rollison, Dana E M

    2006-01-01

    Polyomavirus infection became the focus of epidemiologic studies of cancer several decades ago, soon after the discovery of simian virus 40 (SV40) in 1960 and its ability to induce tumors in experimentally infected animals in 1961. Between 1963 and 2003, eight case-control and eleven cohort studies investigated the possible associations between polyomavirus infection and multiple types of cancer, including lymphoma, brain tumors, and mesothelioma. Two of these studies included measures of infection with the human polyomaviruses, JC virus and BK virus. Overall, the results from these studies were mostly null, although limitations in study design and exposure assessment complicate their interpretation. This chapter includes a review of results from previous epidemiologic studies of polyomavirus infection and human cancer, discussion of the methodologic challenges in study design, and proposed future directions for epidemiologic research.

  10. The Ancient Evolutionary History of Polyomaviruses.

    PubMed

    Buck, Christopher B; Van Doorslaer, Koenraad; Peretti, Alberto; Geoghegan, Eileen M; Tisza, Michael J; An, Ping; Katz, Joshua P; Pipas, James M; McBride, Alison A; Camus, Alvin C; McDermott, Alexa J; Dill, Jennifer A; Delwart, Eric; Ng, Terry F F; Farkas, Kata; Austin, Charlotte; Kraberger, Simona; Davison, William; Pastrana, Diana V; Varsani, Arvind

    2016-04-01

    Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae. PMID:27093155

  11. The Ancient Evolutionary History of Polyomaviruses

    PubMed Central

    Buck, Christopher B.; Van Doorslaer, Koenraad; Peretti, Alberto; Geoghegan, Eileen M.; Tisza, Michael J.; An, Ping; Katz, Joshua P.; Pipas, James M.; McBride, Alison A.; Camus, Alvin C.; McDermott, Alexa J.; Dill, Jennifer A.; Delwart, Eric; Ng, Terry F. F.; Farkas, Kata; Austin, Charlotte; Kraberger, Simona; Davison, William; Pastrana, Diana V.; Varsani, Arvind

    2016-01-01

    Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae. PMID:27093155

  12. The Ancient Evolutionary History of Polyomaviruses.

    PubMed

    Buck, Christopher B; Van Doorslaer, Koenraad; Peretti, Alberto; Geoghegan, Eileen M; Tisza, Michael J; An, Ping; Katz, Joshua P; Pipas, James M; McBride, Alison A; Camus, Alvin C; McDermott, Alexa J; Dill, Jennifer A; Delwart, Eric; Ng, Terry F F; Farkas, Kata; Austin, Charlotte; Kraberger, Simona; Davison, William; Pastrana, Diana V; Varsani, Arvind

    2016-04-01

    Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae.

  13. Report of the second Human Genome Diversity workshop

    SciTech Connect

    1992-12-31

    The Second Human Genome Diversity Workshop was successfully held at Penn State University from October 29--31, 1992. The Workshop was essentially organized around 7 groups, each comprising approximately 10 participants, representing the sampling issues in different regions of the world. These groups worked independently, using a common format provided by the organizers; this was adjusted as needed by the individual groups. The Workshop began with a presentation of the mandate to the participants, and of the procedures to be followed during the workshop. Dr. Feldman presented a summary of the results from the First Workshop. He and the other organizers also presented brief comments giving their perspective on the objectives of the Second Workshop. Dr. Julia Bodmer discussed the study of European genetic diversity, especially in the context of the HLA experience there, and of plans to extend such studies in the coming years. She also discussed surveys of world HLA laboratories in regard to resources related to Human Genome Diversity. Dr. Mark Weiss discussed the relevance of nonhuman primate studies for understanding how demographic processes, such as mate exchange between local groups, affected the local dispersion of genetic variation. Primate population geneticists have some relevant experience in interpreting variation at this local level, in particular, with various DNA fingerprinting methods. This experience may be relevant to the Human Genome Diversity Project, in terms of practical and statistical issues.

  14. Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions: Workshop Report

    NASA Technical Reports Server (NTRS)

    Race, Margaret S. (Editor); Johnson, James E. (Editor); Spry, James A. (Editor); Siegel, Bette; Conley, Catharine A.

    2015-01-01

    This report on Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions summarizes the presentations, deliberations and findings of a workshop at NASA Ames Research Center, March 24-26, 2015, which was attended by more than 100 participants representing a diverse mix of science, engineering, technology, and policy areas. The main objective of the three-day workshop was to identify specific knowledge gaps that need to be addressed to make incremental progress towards the development of NASA Procedural Requirements (NPRs) for Planetary Protection during human missions to Mars.

  15. Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in São Paulo, Brazil.

    PubMed

    Urbano, Paulo Roberto Palma; Oliveira, Renato Reis; Romano, Camila Malta; Pannuti, Claudio Sergio; Fink, Maria Cristina Domingues da Silva

    2016-01-01

    The objective of this study was to evaluate the prevalence, genotypic characterization, and determination of the patterns of shedding of human polyomavirus JC (JCPyV) and BK (BKPyV) in consecutive urine samples collected from healthy adults. Urine samples collected monthly over a 6 month period were screened by polymerase chain reaction (PCR) with two sets of primers complementary to the VP1 protein region specific for the JCPyV or BKPyV genome. The viral load of JCPyV and BKPyV in positive samples was determined by quantitative real time PCR. Seventy-one healthy individuals (ages between 18 and 65) were included in the study. Polyomavirus DNA urinary shedding was identified in 44 (62%) of the 71 individuals evaluated: BKPyV only in 16 (22.5%); JCPyV only in 19 (26.7%); and both in 9 (12.7%). Among the 28 individuals shedding JCPyV, the shedding was nearly continuous in 13 (46.4%) and sporadic in 15 (53.6%), whereas all BKPyV shedding was sporadic. A total of 45 (19 BKPyV and 26 JCPyV) strains were identified. Of the BKPyV strains, individuals were observed that excreted all genotypes except genotype 3 and the JCPyV strains, excretion of 5 different genotypes. Evaluating the age of individuals who excrete JCPyV and BKPyV, mostly are young adults, with a slight increase with increasing age and observing the viral load can not draw any parallel between the increase or decrease of age or excreted genotype as there was a wide variation both in the excretion of BKPyV and JCPyV. The high occurrence of isolated or simultaneous urinary shedding of JCPyV and BKPyV in healthy individuals merits further study.

  16. Exposure to raccoon polyomavirus (RacPyV) in free-ranging North American raccoons (Procyon lotor).

    PubMed

    Church, M E; Dela Cruz, F N; Estrada, M; Leutenegger, C M; Pesavento, P A; Woolard, K D

    2016-02-01

    There is evidence that raccoon polyomavirus is causative for neuroglial brain tumors in the western United States. It is unknown if infection is limited to geographic locales where tumors have been reported or is widespread, like human polyomaviruses. We demonstrate raccoons in western, eastern and midwestern states have been exposed to RacPyV by detection of antibodies to capsid protein, VP1. While raccoons in eastern and midwestern states are seropositive, exposure is lower than in the western states. Additionally, across geographic areas seropositivity is higher in older as compared to younger raccoons, similar to polyomavirus exposure in humans. Serum titers are significantly higher in raccoons with tumors compared to raccoons without. Unlike polyomavirus-associated diseases in humans, we did not detect significant sequence variation between tumor and non-tumor tissue in raccoons with tumors compared to those without tumors. This warrants further investigation into co-morbid diseases or genetic susceptibility studies of the host. PMID:26802526

  17. Exposure to raccoon polyomavirus (RacPyV) in free-ranging North American raccoons (Procyon lotor).

    PubMed

    Church, M E; Dela Cruz, F N; Estrada, M; Leutenegger, C M; Pesavento, P A; Woolard, K D

    2016-02-01

    There is evidence that raccoon polyomavirus is causative for neuroglial brain tumors in the western United States. It is unknown if infection is limited to geographic locales where tumors have been reported or is widespread, like human polyomaviruses. We demonstrate raccoons in western, eastern and midwestern states have been exposed to RacPyV by detection of antibodies to capsid protein, VP1. While raccoons in eastern and midwestern states are seropositive, exposure is lower than in the western states. Additionally, across geographic areas seropositivity is higher in older as compared to younger raccoons, similar to polyomavirus exposure in humans. Serum titers are significantly higher in raccoons with tumors compared to raccoons without. Unlike polyomavirus-associated diseases in humans, we did not detect significant sequence variation between tumor and non-tumor tissue in raccoons with tumors compared to those without tumors. This warrants further investigation into co-morbid diseases or genetic susceptibility studies of the host.

  18. DOE Human Genome Program contractor-grantee workshop

    SciTech Connect

    1996-01-01

    This volume contains the proceedings for the DOE Human Genome Program`s Contractor-Grantee Workshop V held in Sante Fe, New Mexico January 28, February 1, 1996. Presentations were divided into sessions entitled Sequencing; Mapping; Informatics; Ethical, Legal, and Social Issues; and Infrastructure. Reports of individual projects described herein are separately indexed and abstracted for the database.

  19. Fourth international workshop on human chromosome 5. Final progress report

    SciTech Connect

    McPherson, J.D.

    1996-12-31

    The Fourth International Workshop on Human Chromosome 5 was held in Manchester, UK on November 9--10, 1996 and was hosted by the University of Manchester. The major goals of the workshop were: (1) to collate the various genetic, cytogenetic and physical maps of human chromosome 5; (2) to integrate these maps and identify/correct discrepancies between them wherever possible; (3) to catalogue the sequence-ready contigs of the chromosome; (4) to co-ordinate the various sequencing efforts to avoid future duplication; (5) to establish the first (to the author`s knowledge) web site for the human chromosome 5 community which contains the above information in a readily accessible form.

  20. DOE/FDA/EPA: Workshop on methylmercury and human health

    SciTech Connect

    Moskowitz, P.D.; Saroff, L.; Bolger, M.; Cicmanec, J.; Durkee, S.

    1994-12-31

    In the US the general population is exposed to methylmercury (MeHg) principally through the consumption of fish. There is continuing discussion about the sources of this form of mercury (Hg), the magnitudes and trends in exposures to consumers, and the significance of the sources and their contributions to human health. In response to these discussions, the US Department of Energy, the US Food and Drug Administration, and the US Environmental Protection Agency cosponsored a two-day workshop to discuss data and methods available for characterizing the risk to human health presented by MeHg. This workshop was attended by 45 individuals representing various Federal and state organizations and interested stakeholders. The agenda covered: Agency interests; probabilistic approach to risk assessment; emission sources; atmospheric transport; biogeochemical cycling; exposure assessment; health effects of MeHg; and research needs.

  1. The third international workshop of human chromosome 5. Final report

    SciTech Connect

    1994-12-31

    The Third International Workshop on Human Chromosome 5 was held in Laguna Beach, California, March 5-8, 1994. The pace at which new mapping information has been published in the last year make almost any report outdated before publication. Much of the information in this report and the most recent data from the Human chromosome 5 Genome Center at U.C. Irvine on the physical map of chromosome 5 are accessible via a WWW server. For most loci referred to in this report that can be detected by Polymerase Chain Reaction, the sequences of the oligonucleotide primers are available and some primer sequences are provided in this report.

  2. Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study

    PubMed Central

    Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria

    2016-01-01

    Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients. PMID:27242700

  3. Quantitative Proteomic Analysis of Enriched Nuclear Fractions from BK Polyomavirus-Infected Primary Renal Proximal Tubule Epithelial Cells.

    PubMed

    Justice, Joshua L; Verhalen, Brandy; Kumar, Ranjit; Lefkowitz, Elliot J; Imperiale, Michael J; Jiang, Mengxi

    2015-10-01

    Polyomaviruses are a family of small DNA viruses that are associated with a number of severe human diseases, particularly in immunocompromised individuals. The detailed virus-host interactions during lytic polyomavirus infection are not fully understood. Here, we report the first nuclear proteomic study with BK polyomavirus (BKPyV) in a primary renal proximal tubule epithelial cell culture system using stable isotope labeling by amino acids in cell culture (SILAC) proteomic profiling coupled with liquid chromatography-tandem mass spectrometry. We demonstrated the feasibility of SILAC labeling in these primary cells and subsequently performed reciprocal labeling-infection experiments to identify proteins that are altered by BKPyV infection. Our analyses revealed specific proteins that are significantly up- or down-regulated in the infected nuclear proteome. The genes encoding many of these proteins were not identified in a previous microarray study, suggesting that differential regulation of these proteins may be independent of transcriptional control. Western blotting experiments verified the SILAC proteomic findings. Finally, pathway and network analyses indicated that the host cell DNA damage response signaling and DNA repair pathways are among the cellular processes most affected at the protein level during polyomavirus infection. Our study provides a comprehensive view of the host nuclear proteomic changes during polyomavirus lytic infection and suggests potential novel host factors required for a productive polyomavirus infection.

  4. Quantitative Proteomic Analysis of Enriched Nuclear Fractions from BK Polyomavirus-infected Primary Renal Proximal Tubule Epithelial Cells

    PubMed Central

    Justice, Joshua L.; Verhalen, Brandy; Kumar, Ranjit; Lefkowitz, Elliot J.; Imperiale, Michael J.; Jiang, Mengxi

    2016-01-01

    Polyomaviruses are a family of small DNA viruses that are associated with a number of severe human diseases, particularly in immunocompromised individuals. The detailed virus-host interactions during lytic polyomavirus infection are not fully understood. Here we report the first nuclear proteomic study with BK polyomavirus (BKPyV) in a primary renal proximal tubule epithelial cell culture system using stable isotope labeling by amino acids in cell culture (SILAC) proteomic profiling coupled with LC-MS/MS. We demonstrated the feasibility of SILAC labeling in these primary cells and subsequently performed reciprocal labeling-infection experiments to identify proteins that are altered by BKPyV infection. Our analyses revealed specific proteins that are significantly up- or down-regulated in the infected nuclear proteome. The genes encoding many of these proteins were not identified in a previous microarray study, suggesting that differential regulation of these proteins may be independent of transcriptional control. Western blotting experiments verified the SILAC proteomic findings. Finally, pathway and network analyses indicated that the host cell DNA damage response signaling and DNA repair pathways are among the cellular processes most affected at the protein level during polyomavirus infection. Our study provides a comprehensive view of the host nuclear proteomic changes during polyomavirus lytic infection and suggests potential novel host factors required for a productive polyomavirus infection. PMID:26354146

  5. Workshop on Science and the Human Exploration of Mars

    NASA Technical Reports Server (NTRS)

    Duke, M. B. (Editor)

    2001-01-01

    The exploration of Mars will be a multi-decadal activity. Currently, a scientific program is underway, sponsored by NASA's Office of Space Science in the United States, in collaboration with international partners France, Italy, and the European Space Agency. Plans exist for the continuation of this robotic program through the first automated return of Martian samples in 2014. Mars is also a prime long-term objective for human exploration, and within NASA, efforts are being made to provide the best integration of the robotic program and future human exploration missions. From the perspective of human exploration missions, it is important to understand the scientific objectives of human missions, in order to design the appropriate systems, tools, and operational capabilities to maximize science on those missions. In addition, data from the robotic missions can provide critical environmental data - surface morphology, materials composition, evaluations of potential toxicity of surface materials, radiation, electrical and other physical properties of the Martian environment, and assessments of the probability that humans would encounter Martian life forms. Understanding of the data needs can lead to the definition of experiments that can be done in the near-term that will make the design of human missions more effective. This workshop was convened to begin a dialog between the scientific community that is central to the robotic exploration mission program and a set of experts in systems and technologies that are critical to human exploration missions. The charge to the workshop was to develop an understanding of the types of scientific exploration that would be best suited to the human exploration missions and the capabilities and limitations of human explorers in undertaking science on those missions.

  6. Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by immune-mediated diseases under treatment with biologics: an observational study

    PubMed Central

    2013-01-01

    Background Progressive multifocal leukoencephalopathy (PML) onset, caused by Polyomavirus JC (JCPyV) in patients affected by immune-mediated diseases during biological treatment, raised concerns about the safety profile of these agents. Therefore, the aims of this study were the JCPyV reactivation monitoring and the noncoding control region (NCCR) and viral protein 1 (VP1) analysis in patients affected by different immune-mediated diseases and treated with biologics. Methods We performed JCPyV-specific quantitative PCR of biological samples collected at moment of recruitment (t0) and every 4 months (t1, t2, t3, t4). Subsequently, rearrangements’ analysis of NCCR and VP1 was carried out. Data were analyzed using χ2 test. Results Results showed that at t0 patients with chronic inflammatory rheumatic diseases presented a JCPyV load in the urine significantly higher (p≤0.05) than in patients with multiple sclerosis (MS) and Crohn’s disease (CD). It can also be observed a significant association between JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04) in MS patients. Finally, NCCR analysis showed the presence of an archetype-like sequence in all urine samples, whereas a rearranged NCCR Type IR was found in colon-rectal biopsies collected from 2 CD patients after 16 months of infliximab. Furthermore, sequences isolated from peripheral blood mononuclear cells (PBMCs) of 2 MS patients with JCPyV antibody at t0 and t3, showed a NCCR Type IIR with a duplication of a 98 bp unit and a 66 bp insert, resulting in a boxB deletion and 37 T to G transversion into the Spi-B binding site. In all patients, a prevalence of genotypes 1A and 1B, the predominant JCPyV genotypes in Europe, was observed. Conclusions It has been important to understand whether the specific inflammatory scenario in different immune-mediated diseases could affect JCPyV reactivation from latency, in particular from kidneys. Moreover, for a more accurate PML risk stratification

  7. Report on the Second International Workshop on Human Chromosome 9

    SciTech Connect

    Kwiatkowski, D.J.; Armour, J.; Bale, A.E.

    1993-12-31

    The Second International Workshop on Human Chromosome 9 was held in Chatham, Massachusetts on April 18--20, 1993. Fifty-three abstracts were received and the data presented on posters. The purpose of the meeting was to bring together all interested investigators working on the map of chromosome 9, many of whom had disease-specific interests. After a brief presentation of interests and highlighted results, the meeting broke up into the following subgroups for production of consensus maps: 9p; 9cen-q32; 9q32 ter. A global mapping group also met. Reports of each of these working groups is presented in the summary.

  8. Polyomavirus and Naturally Occuring Neuroglial Tumors in Raccoons (Procyon Lotor).

    PubMed

    Pesavento, Patricia A; Brostoff, Terza; Church, Molly E; Dela Cruz, Florante N; Woolard, Kevin D

    2016-01-01

    Polyomavirus (PyV) infections are widespread in human populations and, although generally associated with silent persistence, rarely cause severe disease. Among diseases convincingly associated with natural PyV infections of humans, there are remarkably different tissue tropisms and outcomes, including progressive multifocal leukoencephalopathy, transient or progressive nephropathy, and cancer. The variable character and unpredictable outcomes of infection attest to large gaps in our basic understanding of PyV biology. In particular, the rich history of research demonstrating the oncogenic potential of PyVs in laboratory animals begs the question of why cancer is not more often associated with infection. Raccoon polyomavirus (RacPyV), discovered in 2010, is consistently identified in neuroglial tumors in free-ranging raccoons in the western United States. Exposure to RacPyV is widespread, and RacPyV is detected in tissues of raccoons without tumors. Studying the relationship of RacPyV with its natural host is a unique opportunity to uncover cogent cellular targets and protein interactions between the virus and its host. Our hypothesis is that RacPyV, as an intact episome, alters cellular pathways within neural progenitor cells and drives oncogenesis. PMID:26912716

  9. Polyomavirus and Naturally Occuring Neuroglial Tumors in Raccoons (Procyon Lotor).

    PubMed

    Pesavento, Patricia A; Brostoff, Terza; Church, Molly E; Dela Cruz, Florante N; Woolard, Kevin D

    2016-01-01

    Polyomavirus (PyV) infections are widespread in human populations and, although generally associated with silent persistence, rarely cause severe disease. Among diseases convincingly associated with natural PyV infections of humans, there are remarkably different tissue tropisms and outcomes, including progressive multifocal leukoencephalopathy, transient or progressive nephropathy, and cancer. The variable character and unpredictable outcomes of infection attest to large gaps in our basic understanding of PyV biology. In particular, the rich history of research demonstrating the oncogenic potential of PyVs in laboratory animals begs the question of why cancer is not more often associated with infection. Raccoon polyomavirus (RacPyV), discovered in 2010, is consistently identified in neuroglial tumors in free-ranging raccoons in the western United States. Exposure to RacPyV is widespread, and RacPyV is detected in tissues of raccoons without tumors. Studying the relationship of RacPyV with its natural host is a unique opportunity to uncover cogent cellular targets and protein interactions between the virus and its host. Our hypothesis is that RacPyV, as an intact episome, alters cellular pathways within neural progenitor cells and drives oncogenesis.

  10. WU and KI Polyomaviruses in Respiratory Samples from Allogeneic Hematopoietic Cell Transplant Recipients

    PubMed Central

    Campbell, Angela P.; Guthrie, Katherine A.; Wright, Nancy L.; Englund, Janet A.; Corey, Lawrence; Boeckh, Michael

    2012-01-01

    Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death. PMID:23017213

  11. 76 FR 50221 - International Workshop on Alternative Methods for Human and Veterinary Rabies Vaccine Testing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... scientific experts from government, industry, and academia to review these methods and to define efforts... HUMAN SERVICES International Workshop on Alternative Methods for Human and Veterinary Rabies Vaccine... Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) announces...

  12. Exposing the Molecular Machinery of BK Polyomavirus.

    PubMed

    Buck, Christopher B

    2016-04-01

    BK polyomavirus (BKV) is an opportunistic pathogen that poses a serious threat to organ transplant recipients. In this issue of Structure, Hurdiss and colleagues' (Hurdiss et al., 2016) beautiful new high-resolution cryo-EM reconstruction of BKV provides a structural roadmap for the ongoing development of therapeutic antibodies and vaccines targeting this potentially deadly virus. The study also serves as a platform for exploring the basic biology of virion assembly and infectious entry. PMID:27050683

  13. How Polyomaviruses Exploit the ERAD Machinery to Cause Infection

    PubMed Central

    Dupzyk, Allison; Tsai, Billy

    2016-01-01

    To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases. PMID:27589785

  14. How Polyomaviruses Exploit the ERAD Machinery to Cause Infection.

    PubMed

    Dupzyk, Allison; Tsai, Billy

    2016-01-01

    To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases. PMID:27589785

  15. Workshop meeting report Organs-on-Chips: human disease models.

    PubMed

    van de Stolpe, Anja; den Toonder, Jaap

    2013-09-21

    The concept of "Organs-on-Chips" has recently evolved and has been described as 3D (mini-) organs or tissues consisting of multiple and different cell types interacting with each other under closely controlled conditions, grown in a microfluidic chip, and mimicking the complex structures and cellular interactions in and between different cell types and organs in vivo, enabling the real time monitoring of cellular processes. In combination with the emerging iPSC (induced pluripotent stem cell) field this development offers unprecedented opportunities to develop human in vitro models for healthy and diseased organ tissues, enabling the investigation of fundamental mechanisms in disease development, drug toxicity screening, drug target discovery and drug development, and the replacement of animal testing. Capturing the genetic background of the iPSC donor in the organ or disease model carries the promise to move towards "in vitro clinical trials", reducing costs for drug development and furthering the concept of personalized medicine and companion diagnostics. During the Lorentz workshop (Leiden, September 2012) an international multidisciplinary group of experts discussed the current state of the art, available and emerging technologies, applications and how to proceed in the field. Organ-on-a-chip platform technologies are expected to revolutionize cell biology in general and drug development in particular. PMID:23645172

  16. New areas of focus at workshop on human diseases involving DNA repair deficiency and premature aging.

    PubMed

    Kraemer, Kenneth H; Sander, Miriam; Bohr, Vilhelm A

    2007-02-01

    Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). An important feature of this workshop was the participation of representatives from xeroderma pigmentosum (XP), Cockayne Syndrome (CS) and trichothiodystrophy (TTD) family support groups. Studies presented at the workshop described important new insights into the phenotypic complexity of XP, CS and TTD, renewed focus on the neurological manifestations of each of these diseases, as well as keen interest in the role of oxidative stress and mitochondrial dysfunction in neurodegenerative processes and normal and/or premature aging. This workshop report summarizes some of the presentations and outcomes of the workshop.

  17. Distribution, characterization and significance of polyomavirus genomic sequences in tumors of the brain and its covering.

    PubMed

    Delbue, Serena; Pagani, Elisabetta; Guerini, Franca R; Agliardi, Cristina; Mancuso, Roberta; Borghi, Elisa; Rossi, Francesca; Boldorini, Renzo; Veggiani, Claudia; Car, Pier Giorgio; Ferrante, Pasquale

    2005-11-01

    The etiology of brain tumors and meningiomas is still unknown. Several factors have been considered, such as genetic predisposition and environmental risk factors, but the hypothesis that one or more infectious agents may play a role in tumor pathogenesis has also been investigated. Therefore, emphasis was placed on the neurooncogenic family Polyomaviridae and the presence of human polyomavirus DNA sequences and JCV mRNA were examined in malignant human brain biopsies. Italian patients affected with different types of neoplasias of the brain and its covering were enrolled. The patients underwent surgical tumor excision and the presence of the polyomavirus genome in biopsy and other body fluids was evaluated by PCR. In addition, the genomic organization of JCV was examined in depth, with the aim of providing information on genotype distribution and TCR rearrangements in the population affected with intracranial neoplasms. On the whole, polyomavirus DNA was found in 50% of the biopsy specimens studied, JC virus DNA and BK virus DNA were amplified in 40.6% mainly glioblastomas and 9.4% of the tissue specimens, respectively, while none of the biopsy specimens tested contained Simian virus 40 DNA. Genotype 1 and Mad 4 TCR organization were the most frequent in the population enrolled. Although a cause and effect was not demonstrated and the specific role of the viruses remains unknown, the findings appear to confirm the hypothesis that JCV and BKV could be important co-factors in tumor pathogenesis.

  18. Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease.

    PubMed Central

    Vallbracht, A.; Löhler, J.; Gossmann, J.; Glück, T.; Petersen, D.; Gerth, H. J.; Gencic, M.; Dörries, K.

    1993-01-01

    A 27-year-old man with hemophilia type A and acquired immunodeficiency syndrome developed a subacute meningoencephalitis, associated with a normotensive internal hydrocephalus, 14 weeks before his death. From cerebrospinal fluid and brain autopsy material, a virus could be isolated and was classified by Southern blot analysis and restriction endonuclease reactions as the human polyomavirus BK. The postmortem findings of polyomavirus antigen and BK virus DNA in various cell types of the kidneys, lungs, and central nervous system strongly suggest that BK virus was the causative agent of a tubulointerstitial nephropathy, an interstitial desquamative pneumonitis, and a subacute meningoencephalitis with accentuation of the ventricular and meningeal surfaces of the brain. Besides distinctive cytopathic effects, the presence of intranuclear inclusions was a prominent histopathological feature. Therefore, the human polyomavirus BK should be regarded as a new candidate on the still growing list of opportunistic pathogens in acquired immunodeficiency syndrome. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8391217

  19. The Human Liver Proteome Project (HLPP) Workshop August 2008, Amsterdam, The Netherlands

    PubMed Central

    Beretta, Laura

    2015-01-01

    An HLPP workshop was held in conjunction with the 7th HUPO 2008 World Congress in Amsterdam, The Netherlands. The workshop was chaired by Laura Beretta (Fred Hutchinson Cancer Research Center (FHCRC)) and Xiaohong Qian (Beijing Proteome Research Center (BPRC)). The workshop was organized in three sessions: Session 1: The Human Proteome Project: the liver perspective, moderated by John Bergeron (McGill University); Session 2: The comparative analysis of the liver and plasma proteomes, moderated by Young-Ki Paik (Yonsei University) and Session 3: Opportunities for the study of liver diseases within the HLPP, moderated by Chantal Housset (INSERM, France). PMID:19862759

  20. Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops.

    PubMed

    Fleury, Maxime J J; Nicol, Jérôme T J; Samimi, Mahtab; Arnold, Françoise; Cazal, Raphael; Ballaire, Raphaelle; Mercey, Olivier; Gonneville, Hélène; Combelas, Nicolas; Vautherot, Jean-Francois; Moreau, Thierry; Lorette, Gérard; Coursaget, Pierre; Touzé, Antoine

    2015-01-01

    Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust polyclonal antibody response against the major capsid protein (VP1). However, the polyomavirus VP1 capsid protein epitopes have not been identified to date. The aim of this study was to identify the neutralizing epitopes of the MCPyV capsid. For this goal, four VP1 mutants were generated by insertional mutagenesis in the BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190, and 296-297, respectively. The reactivity of these mutants and wild-type VLPs was then investigated with anti-VP1 monoclonal antibodies and anti-MCPyV positive human sera. The findings together suggest that immunodominant conformational neutralizing epitopes are present at the surface of the MCPyV VLPs and are clustered within BC and EF loops. PMID:25812141

  1. Report of the first international workshop on human chromosome 14 mapping 1993

    SciTech Connect

    Cox, D.W.

    1995-06-01

    The first International Workshop on Human Chromosome 14 mapping was held at Novotel in Toronto, Canada on June 9-12, 1993. There were 23 participants from nine countries. The goals of the workshop were to compile physical maps and a consensus linkage map, to consolidate available data on disease loci, to catalogue and facilitate distribution of resources and to encourage new collaborations and data sharing.

  2. Merkel cell polyomavirus small T antigen is oncogenic in transgenic mice

    PubMed Central

    Harms, Paul W.; Vozheiko, Tracy D.; Weick, Jack W.; Wilbert, Dawn M.; Saunders, Thomas L.; Ermilov, Alexandre N.; Bichakjian, Christopher K.; Johnson, Timothy M.; Imperiale, Michael J.; Dlugosz, Andrzej A.

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare and deadly neuroendocrine skin tumor frequently associated with clonal integration of a polyomavirus, MCPyV, and MCC tumor cells express putative polyomavirus oncoproteins small T antigen (sTAg) and truncated large T antigen (tLTAg). Here, we show robust transforming activity of sTAg in vivo in a panel of transgenic mouse models. Epithelia of pre-term sTAg-expressing embryos exhibited hyperplasia, impaired differentiation, increased proliferation and apoptosis, and activation of a DNA damage response. Epithelial transformation did not require sTAg interaction with the PP2A protein complex, a tumor suppressor in some other polyomavirus transformation models, but was strictly dependent on a recently-described sTAg domain that binds Fbxw7, the substrate-binding component of the SCF ubiquitin ligase complex. Postnatal induction of sTAg using a Cre-inducible transgene also led to epithelial transformation with development of lesions resembling squamous cell carcinoma in situ and elevated expression of Fbxw7 target proteins. Our data establish that expression of MCPyV sTAg alone is sufficient for rapid neoplastic transformation in vivo, implicating sTAg as an oncogenic driver in MCC and perhaps other human malignancies. Moreover, the loss of transforming activity following mutation of the sTAg Fbxw7 binding domain identifies this domain as crucial for in vivo transformation. PMID:25313532

  3. A Novel Polyomavirus (Goose Hemorrhagic Polyomavirus) Is the Agent of Hemorrhagic Nephritis Enteritis of Geese

    PubMed Central

    Guerin, Jean-Luc; Gelfi, Jacqueline; Dubois, Luc; Vuillaume, Aimé; Boucraut-Baralon, Corine; Pingret, Jean-Luc

    2000-01-01

    We have identified the etiological agent of hemorrhagic nephritis enteritis of geese (HNEG), a fatal disease of European geese. HNEG has been recognized in almost all goose breeding areas, with an epizootic pattern, and up to now, the infectious agent has remained unknown. In order to identify the causative agent, infected tissues from HNEG-affected geese were inoculated to 1-day-old goslings, which then developed clinical signs typical of HNEG. Tissue homogenates from these birds were subjected to Freon extraction followed by sucrose density gradient ultracentrifugation. The resulting main band was examined by electron microscopy and consisted of spherical, naked, papovavirus-like particles approximately 45 nm in diameter. The virus was isolated and propagated in goose kidney cell primary culture. Tissue- or culture-purified virus allowed the experimental reproduction of the disease in goslings. Random PCR amplification of viral nucleic acid produced a 1,175-bp fragment which was shown to be associated with field samples collected from geese affected by HNEG on commercial farms in France. Sequence analysis of the PCR product revealed a unique open reading frame, showing 63 to 72% amino acid similarity with the major capsid protein (VP1) of several polyomaviruses. Finally, based on phylogenetic analysis, we conclude that the causative agent of HNEG is closely related to but clearly distinct from other polyomaviruses; we thus have named this newly identified virus Goose hemorrhagic polyomavirus. PMID:10775588

  4. Expression and purification of recombinant polyomavirus VP2 protein and its interactions with polyomavirus proteins

    NASA Technical Reports Server (NTRS)

    Cai, X.; Chang, D.; Rottinghaus, S.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Recombinant polyomavirus VP2 protein was expressed in Escherichia coli (RK1448), using the recombinant expression system pFPYV2. Recombinant VP2 was purified to near homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroelution, and Extracti-Gel chromatography. Polyclonal serum to this protein which reacted specifically with recombinant VP2 as well as polyomavirus virion VP2 and VP3 on Western blots (immunoblots) was produced. Purified VP2 was used to establish an in vitro protein-protein interaction assay with polyomavirus structural proteins and purified recombinant VP1. Recombinant VP2 interacted with recombinant VP1, virion VP1, and the four virion histones. Recombinant VP1 coimmunoprecipitated with recombinant VP2 or truncated VP2 (delta C12VP2), which lacked the carboxy-terminal 12 amino acids. These experiments confirmed the interaction between VP1 and VP2 and revealed that the carboxyterminal 12 amino acids of VP2 and VP3 were not necessary for formation of this interaction. In vivo VP1-VP2 interaction study accomplished by cotransfection of COS-7 cells with VP2 and truncated VP1 (delta N11VP1) lacking the nuclear localization signal demonstrated that VP2 was capable of translocating delta N11VP1 into the nucleus. These studies suggest that complexes of VP1 and VP2 may be formed in the cytoplasm and cotransported to the nucleus for virion assembly to occur.

  5. Human Genome Diversity Project. Summary of planning workshop 3(B): Ethical and human-rights implications

    SciTech Connect

    1993-12-31

    The third planning workshop of the Human Genome Diversity Project was held on the campus of the US National Institutes of Health in Bethesda, Maryland, from February 16 through February 18, 1993. The second day of the workshop was devoted to an exploration of the ethical and human-rights implications of the Project. This open meeting centered on three roundtables, involving 12 invited participants, and the resulting discussions among all those present. Attendees and their affiliations are listed in the attached Appendix A. The discussion was guided by a schedule and list of possible issues, distributed to all present and attached as Appendix B. This is a relatively complete, and thus lengthy, summary of the comments at the meeting. The beginning of the summary sets out as conclusions some issues on which there appeared to be widespread agreement, but those conclusions are not intended to serve as a set of detailed recommendations. The meeting organizer is distributing his recommendations in a separate memorandum; recommendations from others who attended the meeting are welcome and will be distributed by the meeting organizer to the participants and to the Project committee.

  6. Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

    PubMed Central

    Berlingieri, M T; Portella, G; Grieco, M; Santoro, M; Fusco, A

    1988-01-01

    Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene. Images PMID:2838744

  7. Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders

    SciTech Connect

    1995-12-31

    These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for their roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.

  8. The polyomavirus BK agnoprotein co-localizes with lipid droplets

    SciTech Connect

    Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David; Lorentz, Pascal; Rinaldo, Christine H.; Hirsch, Hans H.

    2010-04-10

    Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function.

  9. Efficient propagation of archetype BK and JC polyomaviruses.

    PubMed

    Broekema, Nicole M; Imperiale, Michael J

    2012-01-20

    BKPyV and JCPyV are closely related, ubiquitous human pathogens that cause disease in immunocompromised patients. The DNA sequence of the regulatory regions distinguishes two forms of these viruses, designated archetype and rearranged. Although cell culture systems exist for rearranged BKPyV and JCPyV, currently there is no robust cell culture system to study the archetype viruses. Large T antigen (TAg) is a virally encoded protein required to initiate viral DNA synthesis. Because archetype virus produces undetectable levels of TAg, we hypothesized that TAg overexpression would stimulate archetype virus replication. Efficient propagation of the archetype forms of BKPyV and JCPyV was observed in 293TT cells, human embryonic kidney cells overexpressing SV40 TAg. Importantly, the archetypal structure of the regulatory region was maintained during viral growth. Significant replication was not observed for Merkel cell, KI, or WU polyomaviruses. 293TT cells provide a means of propagating archetype BKPyV and JCPyV for detailed study.

  10. The polyomavirus BK agnoprotein co-localizes with lipid droplets.

    PubMed

    Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David; Lorentz, Pascal; Rinaldo, Christine H; Hirsch, Hans H

    2010-04-10

    Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function. PMID:20138326

  11. Report on the COSPAR Workshop on Refining Planetary Protection Requirements for Human Missions

    NASA Astrophysics Data System (ADS)

    Spry, James Andrew; Rummel, John; Conley, Catharine; Race, Margaret; Kminek, Gerhard; Siegel, Bette

    2016-07-01

    A human mission to Mars has been the driving long-term goal for the development of the Global Exploration Roadmap by the International Space Exploration Coordination Group. Additionally, multiple national space agencies and commercial organizations have published similar plans and aspirations for human missions beyond LEO. The current COSPAR planetary protection "Guidelines for Human Missions to Mars" were developed in a series of workshops in the early 2000s and adopted into COSPAR policy at the Montreal Assembly in 2008. With changes and maturation in mission architecture concepts and hardware capabilities, the holding of a workshop provided an opportunity for timely review of these guidelines and their interpretation within current frameworks provided by ISECG and others. The COSPAR Workshop on Refining Planetary Protection Requirements for Human Missions was held in the US in spring 2016 to evaluate recent efforts and activities in the context of current COSPAR policy, as well as collect inputs from the various organizations considering crewed exploration missions to Mars and precursor robotic missions focused on surface material properties and environmental challenges. The workshop also considered potential updates to the COSPAR policy for human missions across a range of planetary destinations. This paper will report on those deliberations.

  12. Human Factors of Flight-deck Automation: NASA/Industry Workshop

    NASA Technical Reports Server (NTRS)

    Boehm-Davis, D. A.; Curry, R. E.; Wiener, E. L.; Harrison, R. L.

    1981-01-01

    The scope of automation, the benefits of automation, and automation-induced problems were discussed at a workshop held to determine whether those functions previously performed manually on the flight deck of commercial aircraft should always be automated in view of various human factors. Issues which require research for resolution were identified. The research questions developed are presented.

  13. Report of the Second International Workshop on Human Chromosome 5 Mapping

    SciTech Connect

    Westbrook, C.A.; Neuman, W.L.; McPherson, J.; Wasmuth, J.; Camper, S.; Plaetke, R.; Williamson, R.

    1993-12-31

    This report describes the accomplishments of the Second International Workshop on Human Chromosome 5 as was held May 11--13,1992 at the University of Chicago. Included in the report are abstract of individual presentations and a consensus map of the chromosome.

  14. Workshop on Mars 2001: Integrated Science in Preparation for Sample Return and Human Exploration

    NASA Technical Reports Server (NTRS)

    Marshall, John (Editor); Weitz, Cathy (Editor)

    1999-01-01

    The Workshop on Mars 2001: Integrated Science in Preparation for Sample Return and Human Exploration was held on October 2-4, 1999, at the Lunar and Planetary Institute in Houston, Texas. The workshop was sponsored by the Lunar and Planetary Institute, the Mars Program Office of the Jet Propulsion Laboratory, and the National Aeronautics and Space Administration. The three-day meeting was attended by 133 scientists whose purpose was to share results from recent missions, to share plans for the 2001 mission, and to come to an agreement on a landing site for this mission.

  15. Detection of novel polyomaviruses in fruit bats in Indonesia.

    PubMed

    Kobayashi, Shintaro; Sasaki, Michihito; Nakao, Ryo; Setiyono, Agus; Handharyani, Ekowati; Orba, Yasuko; Rahmadani, Ibnu; Taha, Siswatiana; Adiani, Sri; Subangkit, Mawar; Nakamura, Ichiro; Kimura, Takashi; Sawa, Hirofumi

    2015-04-01

    Bats are an important natural reservoir for a variety of viral pathogens, including polyomaviruses (PyVs). The aims of this study were: (i) to determine which PyVs are present in bats in Indonesia and (ii) to analyze the evolutionary relationships between bat PyVs and other known PyVs. Using broad-spectrum polymerase chain reaction (PCR)-based assays, we screened PyV DNA isolated from spleen samples from 82 wild fruit bats captured in Indonesia. Fragments of the PyV genome were detected in 10 of the 82 spleen samples screened, and eight full-length viral genome sequences were obtained using an inverse PCR method. A phylogenetic analysis of eight whole viral genome sequences showed that BatPyVs form two distinct genetic clusters within the proposed genus Orthopolyomavirus that are genetically different from previously described BatPyVs. Interestingly, one group of BatPyVs is genetically related to the primate PyVs, including human PyV9 and trichodysplasia spinulosa-associated PyV. This study has identified the presence of novel PyVs in fruit bats in Indonesia and provides genetic information about these BatPyVs.

  16. Diagnostic Assays for Polyomavirus JC and Progressive Multifocal Leukoencephalopathy

    PubMed Central

    White, Martyn K.; Sariyer, Ilker K.; Gordon, Jennifer; Delbue, Serena; Pietropaolo, Valeria; Berger, Joseph R.; Khalili, Kamel

    2016-01-01

    SUMMARY Progressive multifocal leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system (CNS) for which effective therapies are lacking. It is caused by the replication of polyomavirus JC (JCV) in the oligodendrocytes and astrocytes leading to their cytolytic death and loss of myelin from the subcortical white matter. While the virus is very common in human populations worldwide, the incidence of the disease is very low and confined almost exclusively to individuals with some form of immunological dysfunction. However, the number of people who constitute the at-risk population is growing larger and includes individuals with HIV-1/AIDS and patients receiving immunomodulatory therapies such as multiple sclerosis patients treated with natalizumab. Further adding to the public health significance of this disease are the difficulties encountered in the diagnosis of PML and the lack of useful biomarkers for PML progression. In this review, we examine the diagnostic assays that are available for different aspects of the JCV life cycle, their usefulness and drawbacks, and the prospects for improvements. PMID:26663440

  17. An enhancer of recombination in polyomavirus DNA.

    PubMed Central

    Gendron, D; Delbecchi, L; Bourgaux-Ramoisy, D; Bourgaux, P

    1996-01-01

    Previous work from this laboratory has indicated that intramolecular homologous recombination of polyomavirus (Py) DNA is dependent upon promoter structure or function. In this report, we demonstrate that Py DNA contains not two but three binding sites for transcription factor YY1, all located on the late side of viral origin of replication (ori) and the third well within the VP1 coding sequence. This third site (Y3), which may or may not play a role in transcription regulation, is immediately adjacent to a previously described recombination hot spot (S1/S2). We found that Py replicons carrying an altered Y3 site recombined in a manner suggesting partial inactivation of the S1/S hot spot. Point mutations precluding the binding of YY1 to Y3 in vitro depressed hot spot activity in vivo; however, of the two reciprocal products reflecting recombination at this spot, only that carrying the mutated Y3 site arose at a reduced rate. These results are interpreted in light of a model assuming that recombination occurs within a transcriptionally active viral chromatin tethered to the nuclear matrix by YY1. PMID:8676502

  18. Affordable Exploration of Mars: Recommendations from a Community Workshop on Sustainable Initial Human Missions

    NASA Technical Reports Server (NTRS)

    Thronson, Harley; Carberry, Chris; Cassady, R. J.; Cooke, Doug; Hopkins, Joshua; Perino, Maria A.; Kirkpatrick, Jim; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

    2013-01-01

    There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop.

  19. Human factors of flight-deck automation - Report on a NASA-industry workshop

    NASA Technical Reports Server (NTRS)

    Boehm-Davis, D. A.; Curry, R. E.; Harrison, R. L.; Wiener, E. L.

    1983-01-01

    The scope of automation, the benefits of automation, and automation-induced problems were discussed at a workshop held to determine whether those functions previously performed manually on the flight deck of commercial aircraft should always be automated in view of various human factors. Issues which require research for resolution were identified. The research questions developed are presented. Previously announced in STAR as N81-16022

  20. Polyomavirus origin for DNA replication comprises multiple genetic elements.

    PubMed Central

    Muller, W J; Mueller, C R; Mes, A M; Hassell, J A

    1983-01-01

    To define the minimal cis-acting sequences required for polyomavirus DNA replication (ori), we constructed a number of polyomavirus-plasmid recombinants and measured their replicative capacity after transfection of a permissive mouse cell line capable of providing polyomavirus large T antigen in trans (MOP cells). Recombinant plasmids containing a 251-base-pair fragment of noncoding viral DNA replicate efficiently in MOP cells. Mutational analyses of these viral sequences revealed that they can be physically separated into two genetic elements. One of these elements, termed the core, contains an adenine-thymine-rich area, a 32-base-pair guanine-cytosine-rich palindrome, and a large T antigen binding site, and likely includes the site from which bidirectional DNA replication initiates. The other, termed beta, is located adjacent to the core near the late region and is devoid of outstanding sequence features. Surprisingly, another sequence element named alpha, located adjacent to beta but outside the borders of the 251-base-pair fragment, can functionally substitute for beta. This sequence too contains no readily recognized sequence features and possesses no obvious homology to the beta element. The three elements together occupy a contiguous noncoding stretch of DNA no more than 345 base pairs in length in the order alpha, beta, and core. These results indicate that the polyomavirus origin for DNA replication comprises multiple genetic elements. Images PMID:6312083

  1. Asymmetric Assembly of Merkel Cell Polyomavirus Large T-Antigen Origin Binding Domains at the Viral Origin

    SciTech Connect

    C Harrison; G Meinke; H Kwun; H Rogalin; P Phelan; P Bullock; Y Chang; P Moore; A Bohm

    2011-12-31

    The double-stranded DNA polyomavirus Merkel cell polyomavirus (MCV) causes Merkel cell carcinoma, an aggressive but rare human skin cancer that most often affects immunosuppressed and elderly persons. As in other polyomaviruses, the large T-antigen of MCV recognizes the viral origin of replication by binding repeating G(A/G)GGC pentamers. The spacing, number, orientation, and necessity of repeats for viral replication differ, however, from other family members such as SV40 and murine polyomavirus. We report here the 2.9 {angstrom} crystal structure of the MCV large T-antigen origin binding domain (OBD) in complex with a DNA fragment from the MCV origin of replication. Consistent with replication data showing that three of the G(A/G)GGC-like binding sites near the center of the origin are required for replication, the crystal structure contains three copies of the OBD. This stoichiometry was verified using isothermal titration calorimetry. The affinity for G(A/G)GGC-containing double-stranded DNA was found to be {approx} 740 nM, approximately 8-fold weaker than the equivalent domain in SV40 for the analogous region of the SV40 origin. The difference in affinity is partially attributable to DNA-binding residue Lys331 (Arg154 in SV40). In contrast to SV40, a small protein-protein interface is observed between MCV OBDs when bound to the central region of the origin. This protein-protein interface is reminiscent of that seen in bovine papilloma virus E1 protein. Mutational analysis indicates, however, that this interface contributes little to DNA binding energy.

  2. Asymmetric assembly of Merkel cell polyomavirus large T-antigen origin binding domains at the viral origin.

    PubMed

    Harrison, Celia J; Meinke, Gretchen; Kwun, Hyun Jin; Rogalin, Henry; Phelan, Paul J; Bullock, Peter A; Chang, Yuan; Moore, Patrick S; Bohm, Andrew

    2011-06-17

    The double-stranded DNA polyomavirus Merkel cell polyomavirus (MCV) causes Merkel cell carcinoma, an aggressive but rare human skin cancer that most often affects immunosuppressed and elderly persons. As in other polyomaviruses, the large T-antigen of MCV recognizes the viral origin of replication by binding repeating G(A/G)GGC pentamers. The spacing, number, orientation, and necessity of repeats for viral replication differ, however, from other family members such as SV40 and murine polyomavirus. We report here the 2.9 Å crystal structure of the MCV large T-antigen origin binding domain (OBD) in complex with a DNA fragment from the MCV origin of replication. Consistent with replication data showing that three of the G(A/G)GGC-like binding sites near the center of the origin are required for replication, the crystal structure contains three copies of the OBD. This stoichiometry was verified using isothermal titration calorimetry. The affinity for G(A/G)GGC-containing double-stranded DNA was found to be ~740 nM, approximately 8-fold weaker than the equivalent domain in SV40 for the analogous region of the SV40 origin. The difference in affinity is partially attributable to DNA-binding residue Lys331 (Arg154 in SV40). In contrast to SV40, a small protein-protein interface is observed between MCV OBDs when bound to the central region of the origin. This protein-protein interface is reminiscent of that seen in bovine papilloma virus E1 protein. Mutational analysis indicates, however, that this interface contributes little to DNA binding energy.

  3. Host range and cell cycle activation properties of polyomavirus large T-antigen mutants defective in pRB binding

    SciTech Connect

    Freund, R.; Bauer, P.H.; Benjamin, T.L.; Crissman, H.A.; Bradbury, E.M. |

    1994-11-01

    The authors have examined the growth properties of polyomavirus large T-antigen mutants that ar unable to bind pRB, the product of the retinoblastoma tumor suppressor gene. These mutants grow poorly on primary mouse cells yet grow well on NIH 3T3 and other established mouse cell lines. Preinfection of primary baby mouse kidney (BMK) epithelial cells with wild-type simian virus 40 renders these cells permissive to growth of pRB-binding polyomavirus mutants. Conversely, NIH 3T3 cells transfected by and expressing wild-type human pRB become nonpermissive. Primary fibroblasts for mouse embryos that carry a homozygous knockout of the RB gene are permissive, while those from normal littermates are nonpermissive. The host range of polyomavirus pRB-binding mutants is thus determined by expression or lack of expression of functional pRB by the host. These results demonstrate the importance of pRB binding by large T antigen for productive viral infection in primary cells. Failure of pRB-binding mutants to grow well in BMK cells correlates with their failure to induce progression from G{sub 0} or G{sub 1} through the S phase of the cell cycle. Time course studies show delayed synthesis and lower levels of accumulation of large T antigen, viral DNA, and VP1 in mutant compared with wild-type virus-infected BMK cells. These results support a model in which productive infection by polyomavirus in normal mouse cells is tightly coupled to the induction and progression of the cell cycle. 48 refs., 6 figs., 5 tabs.

  4. New Structural Insights into the Genome and Minor Capsid Proteins of BK Polyomavirus using Cryo-Electron Microscopy.

    PubMed

    Hurdiss, Daniel L; Morgan, Ethan L; Thompson, Rebecca F; Prescott, Emma L; Panou, Margarita M; Macdonald, Andrew; Ranson, Neil A

    2016-04-01

    BK polyomavirus is the causative agent of several diseases in transplant patients and the immunosuppressed. In order to better understand the structure and life cycle of BK, we produced infectious virions and VP1-only virus-like particles in cell culture, and determined their three-dimensional structures using cryo-electron microscopy (EM) and single-particle image processing. The resulting 7.6-Å resolution structure of BK and 9.1-Å resolution of the virus-like particles are the highest-resolution cryo-EM structures of any polyomavirus. These structures confirm that the architecture of the major structural protein components of these human polyomaviruses are similar to previous structures from other hosts, but give new insight into the location and role of the enigmatic minor structural proteins, VP2 and VP3. We also observe two shells of electron density, which we attribute to a structurally ordered part of the viral genome, and discrete contacts between this density and both VP1 and the minor capsid proteins.

  5. Association between the JC polyomavirus infection and male infertility.

    PubMed

    Comar, Manola; Zanotta, Nunzia; Croci, Eleonora; Murru, Immacolata; Marci, Roberto; Pancaldi, Cecilia; Dolcet, Ornella; Luppi, Stefania; Martinelli, Monica; Giolo, Elena; Ricci, Giuseppe; Tognon, Mauro

    2012-01-01

    In recent years the incidence of male infertility has increased. Many risk factors have been taken into consideration, including viral infections. Investigations into viral agents and male infertility have mainly been focused on human papillomaviruses, while no reports have been published on polyomaviruses and male infertility. The aim of this study was to verify whether JC virus and BK virus are associated with male infertility. Matched semen and urine samples from 106 infertile males and 100 fertile males, as controls, were analyzed. Specific PCR analyses were carried out to detect and quantify large T (Tag) coding sequences of JCV and BKV. DNA sequencing, carried out in Tag JCV-positive samples, was addressed to viral protein 1 (VP1) coding sequences. The prevalence of JCV Tag sequences in semen and urine samples from infertile males was 34% (72/212), whereas the BKV prevalence was 0.94% (2/212). Specifically, JCV Tag sequences were detected in 24.5% (26/106) of semen and 43.4% (46/106) of urine samples from infertile men. In semen and urine samples from controls the prevalence was 11% and 28%, respectively. A statistically significant difference (p<0.05) in JCV prevalence was disclosed in semen and urine samples of cases vs. controls. A higher JC viral DNA load was detected in samples from infertile males than in controls. In samples from infertile males the JC virus type 2 strain, subtype 2b, was more prevalent than ubiquitous type 1. JCV type 2 strain infection has been found to be associated with male infertility. These data suggest that the JC virus should be taken into consideration as an infectious agent which is responsible for male infertility.

  6. CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology.

    PubMed

    Engel, Pablo; Boumsell, Laurence; Balderas, Robert; Bensussan, Armand; Gattei, Valter; Horejsi, Vaclav; Jin, Bo-Quan; Malavasi, Fabio; Mortari, Frank; Schwartz-Albiez, Reinhard; Stockinger, Hannes; van Zelm, Menno C; Zola, Heddy; Clark, Georgina

    2015-11-15

    CD (cluster of differentiation) Ags are cell surface molecules expressed on leukocytes and other cells relevant for the immune system. CD nomenclature has been universally adopted by the scientific community and is officially approved by the International Union of Immunological Societies and sanctioned by the World Health Organization. It provides a unified designation system for mAbs, as well as for the cell surface molecules that they recognize. This nomenclature was established by the Human Leukocyte Differentiation Antigens Workshops. In addition to defining the CD nomenclature, these workshops have been instrumental in identifying and determining the expression and function of cell surface molecules. Over the past 30 y, the data generated by the 10 Human Leukocyte Differentiation Antigens Workshops have led to the characterization and formal designation of more than 400 molecules. CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stages. mAbs against these molecules have proven to be essential for biomedical research and diagnosis, as well as in biotechnology. More recently, they have been recognized as invaluable tools for the treatment of several malignancies and autoimmune diseases. In this article, we describe how the CD nomenclature was established, present the official updated list of CD molecules, and provide a rationale for their usefulness in the 21st century. PMID:26546687

  7. Merkel Cell Polyomavirus Small T Antigen Targets the NEMO Adaptor Protein To Disrupt Inflammatory Signaling

    PubMed Central

    Griffiths, David A.; Abdul-Sada, Hussein; Knight, Laura M.; Jackson, Brian R.; Richards, Kathryn; Prescott, Emma L.; Peach, A. Howard S.; Blair, G. Eric

    2013-01-01

    Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKβ-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aβ, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell. PMID:24109239

  8. Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

    PubMed Central

    Jaworska, Joanna S; Comber, M; Auer, C; Van Leeuwen, C J

    2003-01-01

    The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling. PMID:12896859

  9. 75 FR 29775 - Food Labeling Workshop; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... HUMAN SERVICES Food and Drug Administration Food Labeling Workshop; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration... ``Food Labeling Workshop.'' This public workshop is intended to provide information about FDA...

  10. Identification of a Novel Polyomavirus in a Pancreatic Transplant Recipient With Retinal Blindness and Vasculitic Myopathy

    PubMed Central

    Mishra, Nischay; Pereira, Marcus; Rhodes, Roy H.; An, Ping; Pipas, James M.; Jain, Komal; Kapoor, Amit; Briese, Thomas; Faust, Phyllis L.; Lipkin, W. Ian

    2014-01-01

    Background. A 33 year-old pancreatic transplant recipient developed weakness, retinal blindness, and necrotic plaques on her face, scalp, and hands. Methods. A muscle biopsy was analyzed by light and electron microscopy and high-throughput nucleic acid sequencing. Results. The biopsy revealed microthrombosis and viral particles in swollen endothelial cell nuclei. High-throughput sequencing of nucleic acid revealed a novel polyomavirus. In situ hybridization confirmed the presence of the polyomavirus in endothelial cells at sites of myositis and cutaneous necrosis. Conclusions. New Jersey polyomavirus (NJPyV-2013) is a novel polyomavirus that may have tropism for vascular endothelial cells. PMID:24795478

  11. Probiotics in human milk and probiotic supplementation in infant nutrition: a workshop report.

    PubMed

    Bergmann, Henrike; Rodríguez, Juan Miguel; Salminen, Seppo; Szajewska, Hania

    2014-10-14

    Probiotics in human milk are a very recent field of research, as the existence of the human milk microbiome was discovered only about a decade ago. Current research is focusing on bacterial diversity and the influence of the maternal environment as well as the mode of delivery on human milk microbiota, the pathways of bacterial transfer to milk ducts, possible benefits of specific bacterial strains for the treatment of mastitis in mothers, and disease prevention in children. Recent advances in the assessment of early host-microbe interactions suggest that early colonisation may have an impact on later health. This review article summarises a scientific workshop on probiotics in human milk and their implications for infant health as well as future perspectives for infant feeding.

  12. The Science and Issues of Human DNA Polymorphisms: A Training Workshop for High School Biology Teachers

    SciTech Connect

    Micklos, David A.

    2006-10-30

    This project achieved its goal of implementing a nationwide training program to introduce high school biology teachers to the key uses and societal implications of human DNA polymorphisms. The 2.5-day workshop introduced high school biology faculty to a laboratory-based unit on human DNA polymorphisms â which provides a uniquely personal perspective on the science and Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. As proposed, 12 workshops were conducted at venues across the United States. The workshops were attended by 256 high school faculty, exceeding proposed attendance of 240 by 7%. Each workshop mixed theoretical, laboratory, and computer work with practical and ethical implications. Program participants learned simplified lab techniques for amplifying three types of chromosomal polymorphisms: an Alu insertion (PV92), a VNTR (pMCT118/D1S80), and single nucleotide polymorphisms (SNPs) in the mitochondrial control region. These polymorphisms illustrate the use of DNA variations in disease diagnosis, forensic biology, and identity testing - and provide a starting point for discussing the uses and potential abuses of genetic technology. Participants also learned how to use their Alu and mitochondrial data as an entrée to human population genetics and evolution. Our work to simplify lab techniques for amplifying human DNA polymorphisms in educational settings culminated with the release in 1998 of three Advanced Technology (AT) PCR kits by Carolina Biological Supply Company, the nationâÂÂs oldest educational science supplier. The kits use a simple 30-minute method to isolate template DNA from hair sheaths or buccal cells and streamlined PCR chemistry based on Pharmacia Ready-To-Go Beads, which incorporate Taq polymerase, deoxynucleotide triphosphates, and buffer in a freeze-dried pellet. These kits have greatly simplified teacher implementation of human PCR labs, and their use is growing at a rapid pace. Sales of human

  13. The Science and Issues of Human DNA Polymoprhisms: A Training Workshop for High School Biology Teachers

    SciTech Connect

    David. A Micklos

    2006-10-30

    This project achieved its goal of implementing a nationwide training program to introduce high school biology teachers to the key uses and societal implications of human DNA polymorphisms. The 2.5-day workshop introduced high school biology faculty to a laboratory-based unit on human DNA polymorphisms – which provides a uniquely personal perspective on the science and Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. As proposed, 12 workshops were conducted at venues across the United States. The workshops were attended by 256 high school faculty, exceeding proposed attendance of 240 by 7%. Each workshop mixed theoretical, laboratory, and computer work with practical and ethical implications. Program participants learned simplified lab techniques for amplifying three types of chromosomal polymorphisms: an Alu insertion (PV92), a VNTR (pMCT118/D1S80), and single nucleotide polymorphisms (SNPs) in the mitochondrial control region. These polymorphisms illustrate the use of DNA variations in disease diagnosis, forensic biology, and identity testing - and provide a starting point for discussing the uses and potential abuses of genetic technology. Participants also learned how to use their Alu and mitochondrial data as an entrée to human population genetics and evolution. Our work to simplify lab techniques for amplifying human DNA polymorphisms in educational settings culminated with the release in 1998 of three Advanced Technology (AT) PCR kits by Carolina Biological Supply Company, the nation’s oldest educational science supplier. The kits use a simple 30-minute method to isolate template DNA from hair sheaths or buccal cells and streamlined PCR chemistry based on Pharmacia Ready-To-Go Beads, which incorporate Taq polymerase, deoxynucleotide triphosphates, and buffer in a freeze-dried pellet. These kits have greatly simplified teacher implementation of human PCR labs, and their use is growing at a rapid pace. Sales of human polymorphism

  14. Individuals infected with JC polyomavirus do not present detectable JC virus DNA in oropharyngeal fluids.

    PubMed

    Matos, Ana; Duque, Vitor; Luxo, Cristina; Meliço-Silvestre, António; Major, Eugene O

    2012-04-01

    JC virus (JCV) is ubiquitous in the human population. Primary infection normally occurs during childhood and is followed by a lifelong persistent infection. The main mode of transmission remains unknown. Several authors have hypothesized that JCV transmission occurs through the respiratory route, and that respiratory secretions could represent a possible source of viral particles. The present study intended to evaluate oropharyngeal fluids from patients infected with JCV, in order to ascertain if respiratory secretions could indeed constitute a source of exposure to this polyomavirus. Oropharyngeal washing samples from 25 patients co-infected with JCV and human immunodeficiency virus type 1 were evaluated for the presence of JCV DNA. Regardless of the titre of antibodies or the presence of viral urinary excretion, JCV genome was not detected in oropharyngeal samples collected from any of the patients infected with JCV included in this study, which may suggest that oropharyngeal fluids are an unlikely source for JCV infection.

  15. Workshop on Critical Issues in Microgravity Fluids, Transport, and Reaction Processes in Advanced Human Support Technology

    NASA Technical Reports Server (NTRS)

    Chiaramonte, Francis P.; Joshi, Jitendra A.

    2004-01-01

    This workshop was designed to bring the experts from the Advanced Human Support Technologies communities together to identify the most pressing and fruitful areas of research where success hinges on collaborative research between the two communities. Thus an effort was made to bring together experts in both advanced human support technologies and microgravity fluids, transport and reaction processes. Expertise was drawn from academia, national laboratories, and the federal government. The intent was to bring about a thorough exchange of ideas and develop recommendations to address the significant open design and operation issues for human support systems that are affected by fluid physics, transport and reaction processes. This report provides a summary of key discussions, findings, and recommendations.

  16. Human factors issues in the use of artificial intelligence in air traffic control. October 1990 Workshop

    NASA Technical Reports Server (NTRS)

    Hockaday, Stephen; Kuhlenschmidt, Sharon (Editor)

    1991-01-01

    The objective of the workshop was to explore the role of human factors in facilitating the introduction of artificial intelligence (AI) to advanced air traffic control (ATC) automation concepts. AI is an umbrella term which is continually expanding to cover a variety of techniques where machines are performing actions taken based upon dynamic, external stimuli. AI methods can be implemented using more traditional programming languages such as LISP or PROLOG, or they can be implemented using state-of-the-art techniques such as object-oriented programming, neural nets (hardware or software), and knowledge based expert systems. As this technology advances and as increasingly powerful computing platforms become available, the use of AI to enhance ATC systems can be realized. Substantial efforts along these lines are already being undertaken at the FAA Technical Center, NASA Ames Research Center, academic institutions, industry, and elsewhere. Although it is clear that the technology is ripe for bringing computer automation to ATC systems, the proper scope and role of automation are not at all apparent. The major concern is how to combine human controllers with computer technology. A wide spectrum of options exists, ranging from using automation only to provide extra tools to augment decision making by human controllers to turning over moment-by-moment control to automated systems and using humans as supervisors and system managers. Across this spectrum, it is now obvious that the difficulties that occur when tying human and automated systems together must be resolved so that automation can be introduced safely and effectively. The focus of the workshop was to further explore the role of injecting AI into ATC systems and to identify the human factors that need to be considered for successful application of the technology to present and future ATC systems.

  17. Diagnostic methods for and clinical pictures of polyomavirus primary infections in children, Finland.

    PubMed

    Chen, Tingting; Tanner, Laura; Simell, Ville; Hedman, Lea; Mäkinen, Marjaana; Sadeghi, Mohammadreza; Veijola, Riitta; Hyöty, Heikki; Ilonen, Jorma; Knip, Mikael; Toppari, Jorma; Simell, Olli; Söderlund-Venermo, Maria; Hedman, Klaus

    2014-04-01

    We used comprehensive serodiagnostic methods (IgM, IgG, and IgG avidity) and PCR to study Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus infections in children observed from infancy to adolescence. Comparing seroconversion intervals with previous and subsequent intervals, we found that primary infections with these 2 viruses were asymptomatic in childhood.

  18. Characterization of Monoclonal Antibodies Specific for the Merkel Cell Polyomavirus Capsid

    PubMed Central

    Pastrana, Diana V.; Pumphrey, Katherine A.; Çuburu, Nicolas; Schowalter, Rachel M.; Buck, Christopher B.

    2010-01-01

    Merkel cell polyomavirus (MCV) has been implicated as a causative agent in Merkel cell carcinoma. Robust polyclonal antibody responses against MCV have been documented in human subjects, but monoclonal antibodies (mAbs) specific for the VP1 capsid protein have not yet been characterized. We generated 12 mAbs capable of binding recombinant MCV virus-like particles. The use of a short immunogenic priming schedule was important for production of the mAbs. Ten of the 12 mAbs were highly effective for immunofluorescent staining of cells expressing capsid proteins. An overlapping set of 10 mAbs were able to neutralize the infectivity of MCV-based reporter vectors, with 50% effective doses in the low picomolar range. Three mAbs interfered with the binding of MCV virus-like particles to cells. This panel of anti-capsid antibodies should provide a useful set of tools for the study of MCV. PMID:20598728

  19. Characterization of novel polyomaviruses from Bornean and Sumatran orang-utans.

    PubMed

    Groenewoud, Marlous J; Fagrouch, Zahra; van Gessel, Sabine; Niphuis, Henk; Bulavaite, Aiste; Warren, Kristin S; Heeney, Jonathan L; Verschoor, Ernst J

    2010-03-01

    Serological screening of sera from orang-utans demonstrated a high percentage of sera that cross-reacted with antigens of the polyomavirus (PyV) simian virus 40. Analysis of archival DNA samples from 71 Bornean and eight Sumatran orang-utans with a broad-spectrum PCR assay resulted in the detection of PyV infections in 11 animals from both species. Sequence analysis of the amplicons revealed considerable differences between the PyVs from Bornean and Sumatran orang-utans. The genome from two PyVs, one from each species, was therefore amplified and sequenced. Both viral genomes revealed a characteristic PyV architecture, but lacked an obvious agnogene. Neighbour-joining analysis positioned the viruses in a large cluster together with viruses from bats, bovines, rodents and several primate PyVs from chimpanzees, African green monkeys, squirrel monkeys and the human Merkel cell PyV.

  20. Naturally Arising Strains of Polyomaviruses with Severely Attenuated MicroRNA Expression

    PubMed Central

    Chen, Chun Jung; Burke, James M.; Kincaid, Rodney P.; Azarm, Kristopher D.; Mireles, Noel; Butel, Janet S.

    2014-01-01

    ABSTRACT Several different polyomaviruses (PyVs) encode microRNAs (miRNAs) that regulate viral as well as host gene expression. However, the functions of polyomaviral miRNAs, particularly during in vivo infection, remain poorly understood. Here we identify rare naturally arising PyVs that are severely attenuated or null for miRNA expression. We identify hypomorphic or null strains for miRNA expression from rhesus macaque simian virus 40 (SV40) and human JC virus. These strains were isolated from immunocompromised hosts and derive from insertions or deletions in the viral DNA that preserve the amino acid reading frame of opposing-strand large T antigen gene. Characterization of the SV40 miRNA hypomorph, K661, shows that it is inhibited at the early miRNA biogenesis step of Drosha-mediated processing. Despite having a nonrearranged enhancer, which a previous study has shown renders some PyVs more susceptible to the autoregulatory activities of the miRNA, restoring miRNA expression to K661 has little effect on virus growth in either immortalized or primary monkey kidney cells. Thus, in addition to any effect of accompanying genomic elements, these results suggest that the cellular context also determines susceptibility to PyV miRNA-mediated effects. Combined, these results demonstrate that polyomaviruses lacking miRNAs can arise infrequently and that the functional importance of polyomaviral miRNAs is context dependent, consistent with an activity connected to the immune status of the host. IMPORTANCE Diverse virus families encode miRNAs, yet much remains unknown about viral miRNA function and contribution to the infectious cycle. Polyomaviruses (PyVs) are small DNA viruses, long known to be important as etiological agents of rare diseases and valuable models of DNA virus infection. Here, in immunosuppressed hosts, we uncover rare naturally arising variants of different PyVs that have lost the ability to express miRNAs. This represents some of the only known natural

  1. Antarctic Exploration Parallels for Future Human Planetary Exploration: A Workshop Report

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J. (Editor)

    2002-01-01

    Four Antarctic explorers were invited to a workshop at Johnson Space Center (JSC) to provide expert assessments of NASA's current understanding of future human exploration missions beyond low Earth orbit. These explorers had been on relatively sophisticated, extensive Antarctic expeditions with sparse or nonexistent support infrastructure in the period following World War II through the end of the International Geophysical Year. Their experience was similar to that predicted for early Mars or other planetary exploration missions. For example: one Antarctic a expedition lasted two years with only one planned resupply mission and contingency plans for no resupply missions should sea ice prevent a ship from reaching them; several traverses across Antarctica measured more than 1000 total miles, required several months to complete, and were made without maps (because they did not exist) and with only a few aerial photos of the route; and the crews of six to 15 were often international in composition. At JSC, the explorers were given tours of development, training, and scientific facilities, as well as documentation at operational scenarios for future planetary exploration. This report records their observations about these facilities and plans in answers to a series of questions provided to them before the workshop.

  2. Workshop on human health impacts of halogenated biphenyls and related compounds.

    PubMed Central

    Kamrin, M A; Fischer, L J

    1991-01-01

    A workshop on the Human Health Impacts of Halogenated Biphenyls and Related Compounds was held to assess the state of current research on these chemicals and to make recommendations for future studies. Participants discussed results from laboratory animal experiments on PCBs, PBBs, dioxins, and dibenzofurans which demonstrate a common mode of toxicological action while also revealing large variations in toxicological potency both within and between these chemical families. These variations demonstrate the importance of congener-specific analyses in future studies of effects of exposure to these compounds. Results from epidemiological studies of environmentally exposed adult and pediatric populations from the U.S., Japan, and Taiwan and occupationally exposed cohorts from around the world were considered. It was concluded that available evidence did not demonstrate serious adverse effects such as cancer, in exposed adult cohorts but did provide indications of possible neurobehavioral effects in children exposed in utero. In addition, workshop participants described newly developed markers of exposure and techniques for assessing endocrinological, immunological, and neurological effects and suggested these be applied to epidemiological studies of the effects of polyhalogenated compounds. Other recommendations included identification of other cohorts and development of a large registry of exposed individuals; performance of detailed studies of reproductive function and outcomes in exposed populations; and follow up of neurobehavioral effects in offspring of exposed women. PMID:1674906

  3. Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

    PubMed

    Hill, Sarah C; Murphy, Aisling A; Cotten, Matthew; Palser, Anne L; Benson, Phillip; Lesellier, Sandrine; Gormley, Eamonn; Richomme, Céline; Grierson, Sylvia; Bhuachalla, Deirdre Ni; Chambers, Mark; Kellam, Paul; Boschiroli, María-Laura; Ehlers, Bernhard; Jarvis, Michael A; Pybus, Oliver G

    2015-06-01

    Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups. PMID:25626684

  4. Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae

    PubMed Central

    Hill, Sarah C.; Murphy, Aisling A.; Cotten, Matthew; Palser, Anne L.; Benson, Phillip; Lesellier, Sandrine; Gormley, Eamonn; Richomme, Céline; Grierson, Sylvia; Bhuachalla, Deirdre Ni; Chambers, Mark; Kellam, Paul; Boschiroli, María-Laura

    2015-01-01

    Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups. PMID:25626684

  5. Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

    PubMed

    Hill, Sarah C; Murphy, Aisling A; Cotten, Matthew; Palser, Anne L; Benson, Phillip; Lesellier, Sandrine; Gormley, Eamonn; Richomme, Céline; Grierson, Sylvia; Bhuachalla, Deirdre Ni; Chambers, Mark; Kellam, Paul; Boschiroli, María-Laura; Ehlers, Bernhard; Jarvis, Michael A; Pybus, Oliver G

    2015-06-01

    Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.

  6. Summary Report: State-of-the-Science Workshop on Chemically-Induced Mouse Lung Tumors: Applications to Human Health Assessments

    EPA Science Inventory

    The EPA hosted a two-day, state-of-the-science workshop which covered a broad range of evidence from human, animal, and in vitro studies with a focus on specific chemicals (ethylbenzene, naphthalene, and styrene) that cause lung tumors in mice and are implicated in a proposed spe...

  7. BK and JC polyomavirus infections in Tunisian renal transplant recipients.

    PubMed

    Boukoum, Hanen; Nahdi, Imen; Sahtout, Wissal; Skiri, Habib; Aloui, Sabra; Achour, Abdelatif; Segondy, Michel; Aouni, Mahjoub

    2015-10-01

    The aim of this prospective study was to investigate the rate of BK (BKPyV) and JC (JCPyV) polyomavirus infections and their influence on allograft function in Tunisian renal transplant recipients. A total of 72 renal transplant recipients were studied. BKPyV and JCPyV were detected and quantified by real-time PCR in urine and plasma. Demographic and laboratory characteristics were collected for each patient. Polyomavirus DNAuria was detected in 54 (75%) of renal transplant recipients: 26 (36%) had BKPyV DNAuria, 20 (28%) had JCPyV DNAuria, and 8 (11%) had a dual BKPyV/JCPyV DNAuria. BKPyV DNAemia was detected in four (5.5%) patients, whereas no patient had JCPyV viremia. More than 70% of BKPyV and JCPyV infections started within the first 3 months post-transplant. The risk for positive DNAemia was observed in patients with DNAuria level >10(7) copies/ml. BK Polyomavirus-associated nephropathy (BKPyVAN) was observed in two patients. This study highlights the high frequency of BKPyV and JCPyV viruria during the first year post-transplant with the highest incidence observed in the third month. We identified several risk factors that were associated with BKV DNAuria including age, sex of patients, and the use of tacrolimus instead of cyclosporine A at month 3. The use of cyclosporine A instead of tacrolimus was identified as risk factor for JCV viruria in month 3. No statistical difference in the allograft function was found between BKPyV and/or JCPyV infected and uninfected patients.

  8. Interplay of Cellular and Humoral Immune Responses against BK Virus in Kidney Transplant Recipients with Polyomavirus Nephropathy

    PubMed Central

    Chen, Yiping; Trofe, Jennifer; Gordon, Jennifer; Du Pasquier, Renaud A.; Roy-Chaudhury, Prabir; Kuroda, Marcelo J.; Woodle, E. Steve; Khalili, Kamel; Koralnik, Igor J.

    2006-01-01

    Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1p44, and VP1p108. Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1p44) and 5 of 10 (VP1p108) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1p44 were more abundant than against VP1p108 in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1p36 and VP1p100. A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses. PMID:16537617

  9. Gene Regulation and Quality Control in Murine Polyomavirus Infection

    PubMed Central

    Carmichael, Gordon G.

    2016-01-01

    Murine polyomavirus (MPyV) infects mouse cells and is highly oncogenic in immunocompromised hosts and in other rodents. Its genome is a small, circular DNA molecule of just over 5000 base pairs and it encodes only seven polypeptides. While seemingly simply organized, this virus has adopted an unusual genome structure and some unusual uses of cellular quality control pathways that, together, allow an amazingly complex and varied pattern of gene regulation. In this review we discuss how MPyV leverages these various pathways to control its life cycle. PMID:27763514

  10. One Health approach to identify research needs in bovine and human babesioses: workshop report

    PubMed Central

    2010-01-01

    Background Babesia are emerging health threats to humans and animals in the United States. A collaborative effort of multiple disciplines to attain optimal health for people, animals and our environment, otherwise known as the One Health concept, was taken during a research workshop held in April 2009 to identify gaps in scientific knowledge regarding babesioses. The impetus for this analysis was the increased risk for outbreaks of bovine babesiosis, also known as Texas cattle fever, associated with the re-infestation of the U.S. by cattle fever ticks. Results The involvement of wildlife in the ecology of cattle fever ticks jeopardizes the ability of state and federal agencies to keep the national herd free of Texas cattle fever. Similarly, there has been a progressive increase in the number of cases of human babesiosis over the past 25 years due to an increase in the white-tailed deer population. Human babesiosis due to cattle-associated Babesia divergens and Babesia divergens-like organisms have begun to appear in residents of the United States. Research needs for human and bovine babesioses were identified and are presented herein. Conclusions The translation of this research is expected to provide veterinary and public health systems with the tools to mitigate the impact of bovine and human babesioses. However, economic, political, and social commitments are urgently required, including increased national funding for animal and human Babesia research, to prevent the re-establishment of cattle fever ticks and the increasing problem of human babesiosis in the United States. PMID:20377902

  11. 76 FR 60505 - Food Defense Workshop; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... HUMAN SERVICES Food and Drug Administration Food Defense Workshop; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA), Office of... M. Kerr Food & Agricultural Products Center (FAPC), is announcing a public workshop entitled...

  12. Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop

    PubMed Central

    Rodriguez, Blanca; Carusi, Annamaria; Abi-Gerges, Najah; Ariga, Rina; Britton, Oliver; Bub, Gil; Bueno-Orovio, Alfonso; Burton, Rebecca A.B.; Carapella, Valentina; Cardone-Noott, Louie; Daniels, Matthew J.; Davies, Mark R.; Dutta, Sara; Ghetti, Andre; Grau, Vicente; Harmer, Stephen; Kopljar, Ivan; Lambiase, Pier; Lu, Hua Rong; Lyon, Aurore; Minchole, Ana; Muszkiewicz, Anna; Oster, Julien; Paci, Michelangelo; Passini, Elisa; Severi, Stefano; Taggart, Peter; Tinker, Andy; Valentin, Jean-Pierre; Varro, Andras; Wallman, Mikael; Zhou, Xin

    2016-01-01

    Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting. PMID:26622055

  13. Mycobacterium genavense and avian polyomavirus co-infection in a European goldfinch (Carduelis carduelis).

    PubMed

    Manarolla, G; Liandris, E; Pisoni, G; Moroni, P; Piccinini, R; Rampin, T

    2007-10-01

    Systemic mycobacteriosis associated with avian polyomavirus infection was diagnosed histologically in an 8-year-old, captive European goldfinch with a history of nervous signs. Severe mycobacterial lesions were observed in the central nervous system, lungs, cervical air sacs and adrenal glands, without involvement of the gastrointestinal tract. In addition to mycobacteriosis, intranuclear inclusions, typical of polyomavirus, were identified in the adrenal glands. Polymerase chain reaction assays were used to identify Mycobacterium genavense and finch polyomavirus as the causative agents. The absence of involvement of the gastrointestinal tract and the severity of the lesions in the respiratory tract suggested that inhalation may have been the primary route of infection with M. genavense.

  14. Polyomavirus infection in budgerigars (Melopsittacus undulatus): clinical and aetiological studies.

    PubMed

    Krautwald, M E; Müller, H; Kaleta, E F

    1989-08-01

    In order to get insight into the aetiology of French Moult (FM) and Budgerigar Fledgling Disease (BFD), and to determine relationships between the two diseases, 298 budgerigars from 49 different breeding flocks were examined. From all birds with BFD and from several birds with FM, viruses were isolated which produced characteristic cytopathic changes in chicken embryo fibroblasts. They were insensitive to chloroform treatment, and their replication was inhibited in the presence of 5-iododeoxyuridine. One of these isolates, from a bird exhibiting clinical signs of BFD, was determined by biochemical and biophysical methods to be a polyomavirus (BFDV). Nestling budgerigars 3 to 10 days of age, were inoculated with this BFDV isolate. They developed an acute systemic disease with high mortality rates, similar to naturally occurring infections. In this regard, BFDV differs markedly from all the other polyomaviruses known until now which only cause clinically asymptomatic, persistent infections in their natural hosts. Most of the birds examined with clinical signs of BFD or FM exhibited low titers of antibodies neutralizing the BFDV isolate, whereas in clinically healthy birds from flocks that never had any problems with FM or BFD, no antibodies against BFDV could be detected. On account of the results of our experiments described here we suspect that FM might be a milder, more protracted form of a BFDV infection. PMID:2552708

  15. A case of primary JC polyomavirus infection-associated nephropathy.

    PubMed

    Lautenschlager, I; Jahnukainen, T; Kardas, P; Lohi, J; Auvinen, E; Mannonen, L; Dumoulin, A; Hirsch, H H; Jalanko, H

    2014-12-01

    A 15-year-old boy with a posterior urethral valve received a deceased donor kidney transplant (KT) in March 2011. Basiliximab induction followed by tacrolimus-based triple medication was used as immunosuppression. Eleven months after KT, the graft function deteriorated and the biopsy demonstrated interstitial nephritis suggestive of acute rejection. BK polyomavirus (BKPyV) surveillance in urine and plasma was negative. The patient received methylprednisolone pulses and anti-thymocyte globulin. Immunohistochemistry was positive for simian virus 40 (SV40) large T-antigen (LTag) in the biopsies, and quantitative polymerase chain reaction for JC polyomavirus (JCPyV) indicated high viral loads in urine and borderline levels in plasma. Immunosuppression was reduced and follow-up biopsies showed tubular atrophy and interstitial fibrosis. Two years after KT, antibody-mediated rejection resulted in graft loss and return to hemodialysis. Retrospective serologic work-up indicated a primary JCPyV infection with seroconversion first for IgM, followed by IgG, but no indication of BKPyV infection. In the SV40 LTag positive biopsies, JCPyV deoxyribonucleic acid (DNA) with archetype noncoding control region was detected, while BKPyV DNA was undetectable. To the best of our knowledge, this is the first reported case of primary JCPyV infection as the cause of PyV-associated nephropathy in KT. PMID:25359127

  16. Characterization of the DNA binding properties of polyomavirus capsid protein

    NASA Technical Reports Server (NTRS)

    Chang, D.; Cai, X.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    The DNA binding properties of the polyomavirus structural proteins VP1, VP2, and VP3 were studied by Southwestern analysis. The major viral structural protein VP1 and host-contributed histone proteins of polyomavirus virions were shown to exhibit DNA binding activity, but the minor capsid proteins VP2 and VP3 failed to bind DNA. The N-terminal first five amino acids (Ala-1 to Lys-5) were identified as the VP1 DNA binding domain by genetic and biochemical approaches. Wild-type VP1 expressed in Escherichia coli (RK1448) exhibited DNA binding activity, but the N-terminal truncated VP1 mutants (lacking Ala-1 to Lys-5 and Ala-1 to Cys-11) failed to bind DNA. The synthetic peptide (Ala-1 to Cys-11) was also shown to have an affinity for DNA binding. Site-directed mutagenesis of the VP1 gene showed that the point mutations at Pro-2, Lys-3, and Arg-4 on the VP1 molecule did not affect DNA binding properties but that the point mutation at Lys-5 drastically reduced DNA binding affinity. The N-terminal (Ala-1 to Lys-5) region of VP1 was found to be essential and specific for DNA binding, while the DNA appears to be non-sequence specific. The DNA binding domain and the nuclear localization signal are located in the same N-terminal region.

  17. Reporting of the third international workshop on human chromosome 22 mapping

    SciTech Connect

    Emanuel, B.S.; Buetow, K.; Nussbaum, R.; Scambler, P; Lipinski, M.; Overton, C.

    1992-12-31

    The third international workshop on the mapping of human chromosome 22 was held at the Sugarloaf Conference Center in Philadelphia Pennsylvania USA from September 17--20, 1992. It was organized by Beverly S. Emanuel of Children`s Hospital of Philadelphia and the Human Genome Center for Chromosome 22. The highlights of the conference included the discussion of the chromosome 22 gene at the Ewings Sarcoma breakpoint, the identification of a polymorphic TG/CA repeat containing locus tightly linked to the NF2 gene, the isolation of a candidate tumor suppressor locus for meningioma, the isolation of numerous as yet uncharacterized new cDNAs for chromosome 22 and the progress which has been made on generating physical and genetic maps of the chromosome. There is a new genetic map comprised of 16 short tandem repeat polymorphism (STRP) markers of which 12 have greater than 70% heterozygosity (Fig. 1). It was decided that the next meeting should be held in 18 months and it will be organized by Peter Scambler in the United Kingdom.

  18. Rapid detection of trichodysplasia spinulosa-associated polyomavirus in skin biopsy specimen.

    PubMed

    Urbano, Paulo Roberto P; Pannuti, Cláudio Sérgio; Pierrotti, Ligia C; David-Neto, Elias; Romano, Camila Malta

    2014-07-24

    Trichodysplasia spinulosa-associated polyomavirus (TSV) is responsible for a rare skin cancer. Using metagenomic approaches, we determined the complete genome sequence of a TSV first detected in Brazil in spicules of an immunocompromised patient suspected to have trichodysplasia spinulosa.

  19. Merkel cell polyomavirus small T antigen mRNA level is increased following in vivo UV-radiation.

    PubMed

    Mogha, Ariane; Fautrel, Alain; Mouchet, Nicolas; Guo, Na; Corre, Sébastien; Adamski, Henri; Watier, Eric; Misery, Laurent; Galibert, Marie-Dominique

    2010-07-02

    Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer involving Merkel cells. Recently, a new human polyomavirus was implicated in MCC, being present in 80% of the samples analyzed. In virus-positive MCC, the Merkel cell polyomavirus (MCPyV) is clonally integrated into the patients DNA, and carries mutations in its large T antigen, leading to a truncated protein. In non-symptomatic tissue MCPyV can reside at very low levels. MCC is also associated with older age, immunosuppression and sun exposure. However, the link with solar exposure remains unknown, as the precise mechanism and steps involved between time of infection by MCPyV and the development of MCC. We thus investigated the potential impact of solar simulated radiation (SSR) on MCPyV transcriptional activity. We screened skin samples of 20 healthy patients enrolled in a photodermatological protocol based on in vivo-administered 2 and 4 J/cm(2) SSR. Two patients were infected with two new variants of MCPyV, present in their episomal form and RT-QPCR analyses on SSR-irradiated skin samples showed a specific and unique dose-dependent increase of MCPyV small t antigen transcript. A luciferase based in vitro assay confirmed that small t promoter is indeed UV-inducible. These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure.

  20. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    PubMed

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.

  1. Accelerating the development of 21st-century toxicology: outcome of a Human Toxicology Project Consortium workshop.

    PubMed

    Stephens, Martin L; Barrow, Craig; Andersen, Melvin E; Boekelheide, Kim; Carmichael, Paul L; Holsapple, Michael P; Lafranconi, Mark

    2012-02-01

    The U.S. National Research Council (NRC) report on "Toxicity Testing in the 21st century" calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to "toxicity pathways," i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report's implementation, the Human Toxicology Project Consortium hosted a workshop on 9-10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities.

  2. Report of the first international workshop on human chromosome 8 mapping. Final report

    SciTech Connect

    Wood, S.; Ben Othmane, K.; Bergerheim, U.S.R.

    1993-12-31

    The first international chromosome 8 workshop was held in Vancouver, Canada May 2--4, 1993. The conference was attended by 23 participants from Australia, Canada, Germany, the Netherlands, Sweden, the United Kingdom and the US. Twenty three abstracts are included from this workshop. The workshop was supported by CGAT/CTAG (Canadian Genome Analysis & Technology Program/Programme Canadien de Technologie & D`Analyse du Genome) as well as by travel funds allocated by the National Institutes of Health and the Department of Energy of the United States and by agencies within the countries of overseas participants. The goals of the workshop were to evaluate new locus assignments, review new data obtained for previously assigned loci, develop a consensus marker order for chromosome 8, assess and integrate physical mapping information, identify resources and foster collaboration.

  3. Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK.

    PubMed

    Randhawa, P; Pastrana, D V; Zeng, G; Huang, Y; Shapiro, R; Sood, P; Puttarajappa, C; Berger, M; Hariharan, S; Buck, C B

    2015-04-01

    Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

  4. Workshop 7 (synthesis): towards a recycling society: systems approach to small-scale reuse of human waste.

    PubMed

    Rahman, A; Drangert, J O

    2001-01-01

    Population increase and growing quantities of human excreta create serious problems and high risks for people's health. Alternative solutions are becoming crucial to improve urban living conditions, and to shorten water and nutrient flows into circulation of used water and nutrient in human excreta. The speakers presented a wide range of experiences of "closing the loops" and thereby turning potential waste into productive use. The focus of the workshop deliberations was on simplifying the hygienisation of urine and faeces and the reuse in food production by using urine-diverting toilets, as well as innovative ways to recycle sewage after various stages of treatment.

  5. The Human Dimension of Teacher Education [for the 21st Century]. Proceedings of the Annual Summer Workshop of the North Central Accrediting Association and the American Association of Colleges for Teacher Education (37th, Muncie, Indiana, July-August, 1984).

    ERIC Educational Resources Information Center

    Jones, Donald W., Ed.

    This document contains written summaries of workshop activities which took place at the 1984 summer workshop sponsored by the North Central Association of Colleges and Schools. The theme of the workshop was "The Human Dimension of Teacher Education for the 21st Century." Following a description of the background, structure, and objectives of the…

  6. Advanced Technologies for Robotic Exploration Leading to Human Exploration: Results from the SpaceOps 2015 Workshop

    NASA Technical Reports Server (NTRS)

    Lupisella, Mark L.; Mueller, Thomas

    2016-01-01

    This paper will provide a summary and analysis of the SpaceOps 2015 Workshop all-day session on "Advanced Technologies for Robotic Exploration, Leading to Human Exploration", held at Fucino Space Center, Italy on June 12th, 2015. The session was primarily intended to explore how robotic missions and robotics technologies more generally can help lead to human exploration missions. The session included a wide range of presentations that were roughly grouped into (1) broader background, conceptual, and high-level operations concepts presentations such as the International Space Exploration Coordination Group Roadmap, followed by (2) more detailed narrower presentations such as rover autonomy and communications. The broader presentations helped to provide context and specific technical hooks, and helped lay a foundation for the narrower presentations on more specific challenges and technologies, as well as for the discussion that followed. The discussion that followed the presentations touched on key questions, themes, actions and potential international collaboration opportunities. Some of the themes that were touched on were (1) multi-agent systems, (2) decentralized command and control, (3) autonomy, (4) low-latency teleoperations, (5) science operations, (6) communications, (7) technology pull vs. technology push, and (8) the roles and challenges of operations in early human architecture and mission concept formulation. A number of potential action items resulted from the workshop session, including: (1) using CCSDS as a further collaboration mechanism for human mission operations, (2) making further contact with subject matter experts, (3) initiating informal collaborative efforts to allow for rapid and efficient implementation, and (4) exploring how SpaceOps can support collaboration and information exchange with human exploration efforts. This paper will summarize the session and provide an overview of the above subjects as they emerged from the SpaceOps 2015

  7. Genome Sequences of Polyomaviruses from the Wild-Living Red Colobus (Piliocolobus badius) and Western Chimpanzee (Pan troglodytes verus)

    PubMed Central

    Ben Salem, Nicole; Leendertz, Fabian H.

    2016-01-01

    We identified with PCR and sequencing the full genomes of the recently discovered Pan troglodytes verus polyomavirus 8 and Piliocolobus badius polyomavirus 2 in a western chimpanzee and a western red colobus free-ranging in Taï National Park of Côte d’Ivoire. PMID:27738028

  8. Polyomavirus BK Induces Inflammation via Up-regulation of CXCL10 at Translation Levels in Renal Transplant Patients with Nephropathy.

    PubMed

    Kariminik, Ashraf; Dabiri, Shahriar; Yaghobi, Ramin

    2016-08-01

    Polyomavirus BK-associated nephropathy (BKAN) is an important mechanism for renal losing after kidney transplantation. It seems that Polyomavirus BK can induce nephropathy by direct cell lysis and stimulation of the immune system and induction of inflammation. CXCL10 is a pro-inflammatory cytokine which stimulates the migration and activation of immune cells to the infected sites. Therefore, the aim of the current study was to evaluate the messenger RNA (mRNA) and protein levels of CXCL10 in the Polyomavirus BK-infected and Polyomavirus BK-non-infected post renal transplanted nephropathic patients in comparison to healthy controls. In this cross-sectional study, Polyomavirus BK-infected post renal transplanted nephropathic patients, Polyomavirus BK-non-infected post renal transplanted nephropathic patients, and healthy controls were enrolled to evaluate mRNA and protein levels of CXCL10 by real-time PCR and ELISA techniques, respectively. mRNA levels of CXCL10 were not significantly different among participants, while serum levels of CXCL10 were significantly elevated in the Polyomavirus BK-infected patients when compared to non-infected patients as well as controls and in non-infected patients when compared to healthy controls. Due to the results, it seems that Polyomavirus BK may potentially induce renal losing through stimulation of inflammation via increasing translation of CXCL10, as a pro-inflammatory chemokine.

  9. Differential Sensitivity of Mouse Epithelial Tissues to the Polyomavirus Middle T Oncogene

    PubMed Central

    Cecena, Grace; Wen, Fang; Cardiff, Robert D.; Oshima, Robert G.

    2006-01-01

    To determine how different epithelial cell types respond to the same oncogenic stimulation, we have used a modified human keratin 18 gene to conditionally express the polyomavirus middle T antigen (PyMT) oncogene in simple epithelial tissues of transgenic mice. Activation of PyMT expression by transgenic Cre recombinase in mammary epithelial cells resulted in carcinomas in all bitransgenic females. PyMT expression induced by K18-driven Cre in internal epithelial organs resulted in pancreatic acinar metaplasia and ductal dysplasia with remarkable desmoplastic stromal responses in all 25 bitransgenic mice. Hepatoma formation with altered lipid metabolism and gastric adenocarcinoma occurred in 96 and 54% of these mice, respectively. Elevated PyMT RNA expression also correlated with intraepithelial neoplasia in the prostate. Activated Erk2 was found in mammary tumors, pancreatic tissues, and affected livers. Hes1 RNA, a target of Notch signaling that has been implicated downstream of Ras pathway activation, was elevated in pancreatic and liver lesions. The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals. PMID:16400032

  10. NASA Workshop on Technology for Human Robotic Exploration and Development of Space

    NASA Technical Reports Server (NTRS)

    Mankins, J. C.; Marzwell, N.; Mullins, C. A.; Christensen, C. B.; Howell, J. T.; O'Neil, D. A.

    2004-01-01

    Continued constrained budgets and growing interests in the industrialization and development of space requires NASA to seize every opportunity for assuring the maximum return on space infrastructure investments. This workshop provided an excellent forum for reviewing, evaluating, and updating pertinent strategic planning, identifying advanced concepts and high-risk/high-leverage research and technology requirements, developing strategies and roadmaps, and establishing approaches, methodologies, modeling, and tools for facilitating the commercial development of space and supporting diverse exploration and scientific missions. Also, the workshop addressed important topic areas including revolutionary space systems requiring investments in innovative advanced technologies; achieving transformational space operations through the insertion of new technologies; revolutionary science in space through advanced systems and new technologies enabling experiments to go anytime to any location; and, innovative and ambitious concepts and approaches essential for promoting advancements in space transportation. Details concerning the workshop process, structure, and results are contained in the ensuing report.

  11. Does polyomavirus infection interfere with bladder cancer fluorescence in situ hybridization?

    PubMed

    Hossain, Deloar; Hull, David; Kalantarpour, Fatemeh; Maitlen, Rebecca; Qian, Junqi; Bostwick, David G

    2014-03-01

    Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection. PMID:24006232

  12. Does polyomavirus infection interfere with bladder cancer fluorescence in situ hybridization?

    PubMed

    Hossain, Deloar; Hull, David; Kalantarpour, Fatemeh; Maitlen, Rebecca; Qian, Junqi; Bostwick, David G

    2014-03-01

    Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection.

  13. Summary of the International Workshop of Dietary Sodium and Human Health in China and the United States.

    PubMed

    Alderman, Michael H

    2009-09-01

    The idea for a workshop focused on sodium and health was generated by the editors of the American Journal of Hypertension and the Chinese Journal of Hypertension as part of their emerging collaboration. It reflects a belief that scientists and clinicians interested in blood pressure and its related conditions would profit from more effective communication and interaction. Salt was chosen as a central topic because of its multiple physiological and pathological effects, its importance to human health, its role in elevating blood pressure, the unresolved scientific issues, and the absence of an agreed public health response regarding dietary sodium. In addition, much current clinical and population research has begun to shed light on how the interaction of genetics, environment, and diet determines the impact of sodium intake on human health and disease. Surprisingly, given the often passionate professional interest, there has been no regular forum dedicated to an exchange of new knowledge and current research findings. The biomedical literature provides strong evidence that investigators around the world are generating important new findings that increase understanding of how dietary sodium may relate to both health and disease. Given the widely shared need and interest, the workshop's organizers hope that the experience in Xi'an will lead to the appearance of regular working meetings on sodium and human disease on the international scientific schedule. The ultimate goal is for this scientific discourse to lead to evidence-based programs for population salt consumption that will contribute to the betterment of human health.

  14. Summary of the International Workshop of Dietary Sodium and Human Health in China and the United States.

    PubMed

    Alderman, Michael H

    2009-09-01

    The idea for a workshop focused on sodium and health was generated by the editors of the American Journal of Hypertension and the Chinese Journal of Hypertension as part of their emerging collaboration. It reflects a belief that scientists and clinicians interested in blood pressure and its related conditions would profit from more effective communication and interaction. Salt was chosen as a central topic because of its multiple physiological and pathological effects, its importance to human health, its role in elevating blood pressure, the unresolved scientific issues, and the absence of an agreed public health response regarding dietary sodium. In addition, much current clinical and population research has begun to shed light on how the interaction of genetics, environment, and diet determines the impact of sodium intake on human health and disease. Surprisingly, given the often passionate professional interest, there has been no regular forum dedicated to an exchange of new knowledge and current research findings. The biomedical literature provides strong evidence that investigators around the world are generating important new findings that increase understanding of how dietary sodium may relate to both health and disease. Given the widely shared need and interest, the workshop's organizers hope that the experience in Xi'an will lead to the appearance of regular working meetings on sodium and human disease on the international scientific schedule. The ultimate goal is for this scientific discourse to lead to evidence-based programs for population salt consumption that will contribute to the betterment of human health. PMID:19701162

  15. Proposed Methodology for Developing a National Strategy for Human Resource Development: Lessons Learned from a NNSA Workshop

    SciTech Connect

    Elkhamri, Oksana O.; Frazar, Sarah L.; Essner, Jonathan; Vergino, Eileen; Bissani, Mo; Apt, Kenneth E.; McClelland-Kerr, John; Mininni, Margot; VanSickle, Matthew; Kovacic, Donald

    2009-10-07

    This paper describes a recent National Nuclear Security Administration (NNSA) workshop on Human Resource Development, which was focused on the potential methodology for developing a National Human Resource strategy for nuclear power in emerging nuclear states. The need for indigenous human resource development (HRD) has been singled out as a key milestone by the International Atomic Energy Agency (IAEA) in its 2007 Milestones document. A number of countries considering nuclear energy have reiterated this need for experts and specialists to support a national nuclear program that is sustainable and secure. Many have expressed concern over how best to assure the long-term availability of crucial human resource, how to approach the workforce planning process, and how to determine the key elements of developing a national strategy.

  16. 75 FR 25281 - Food Protection Workshop; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-07

    ... HUMAN SERVICES Food and Drug Administration Food Protection Workshop; Public Workshop AGENCY: Food and Drug Administration, HHS. ] ACTION: Notice of public workshop. SUMMARY: The Food and Drug... with the University of Arkansas (UA) Institute of Food Science and Engineering, is announcing a...

  17. 77 FR 12313 - Food Labeling Workshop; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... HUMAN SERVICES Food and Drug Administration Food Labeling Workshop; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA... University (OSU), Robert M. Kerr Food & Agricultural Products Center (FAPC), is announcing a public...

  18. Report of the Fourth International Workshop on human X chromosome mapping 1993

    SciTech Connect

    Schlessinger, D.; Mandel, J.L.; Monaco, A.P.; Nelson, D.L.; Willard, H.F.

    1993-12-31

    Vigorous interactive efforts by the X chromosome community have led to accelerated mapping in the last six months. Seventy-five participants from 12 countries around the globe contributed progress reports to the Fourth International X Chromosome Workshop, at St. Louis, MO, May 9-12, 1993. It became clear that well over half the chromosome is now covered by YAC contigs that are being extended, verified, and aligned by their content of STSs and other markers placed by cytogenetic or linkage mapping techniques. The major aim of the workshop was to assemble the consensus map that appears in this report, summarizing both consensus order and YAC contig information.

  19. Modulation of a Pore in the Capsid of JC Polyomavirus Reduces Infectivity and Prevents Exposure of the Minor Capsid Proteins

    PubMed Central

    Nelson, Christian D. S.; Ströh, Luisa J.; Gee, Gretchen V.; O'Hara, Bethany A.; Stehle, Thilo

    2015-01-01

    ABSTRACT JC polyomavirus (JCPyV) infection of immunocompromised individuals results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). The viral capsid of JCPyV is composed primarily of the major capsid protein virus protein 1 (VP1), and pentameric arrangement of VP1 monomers results in the formation of a pore at the 5-fold axis of symmetry. While the presence of this pore is conserved among polyomaviruses, its functional role in infection or assembly is unknown. Here, we investigate the role of the 5-fold pore in assembly and infection of JCPyV by generating a panel of mutant viruses containing amino acid substitutions of the residues lining this pore. Multicycle growth assays demonstrated that the fitness of all mutants was reduced compared to that of the wild-type virus. Bacterial expression of VP1 pentamers containing substitutions to residues lining the 5-fold pore did not affect pentamer assembly or prevent association with the VP2 minor capsid protein. The X-ray crystal structures of selected pore mutants contained subtle changes to the 5-fold pore, and no other changes to VP1 were observed. Pore mutant pseudoviruses were not deficient in assembly, packaging of the minor capsid proteins, or binding to cells or in transport to the host cell endoplasmic reticulum. Instead, these mutant viruses were unable to expose VP2 upon arrival to the endoplasmic reticulum, a step that is critical for infection. This study demonstrated that the 5-fold pore is an important structural feature of JCPyV and that minor modifications to this structure have significant impacts on infectious entry. IMPORTANCE JCPyV is an important human pathogen that causes a severe neurological disease in immunocompromised individuals. While the high-resolution X-ray structure of the major capsid protein of JCPyV has been solved, the importance of a major structural feature of the capsid, the 5-fold pore, remains poorly understood. This pore is conserved across

  20. REPORT ON WORKSHOP ON SUSTAINABILITY AND INDUSTRY: ENERGY, MATERIAL CONSUMPTION, AND HUMAN BEHAVIOR

    EPA Science Inventory

    The purpose of the Workshop was to begin a process by which the leaders of the Council for Chemical Research, industry, academia, and government focus on sustainability and devote substantial resources to advancing issues that will improve the sustainability of industry and socie...

  1. Report of the fifth international workshop on human X chromosome mapping

    SciTech Connect

    Willard, H.F.; Cremers, F.; Mandel, J.L.; Monaco, A.P.; Nelson, D.L.; Schlessinger, D.

    1994-12-31

    A high-quality integrated genetic and physical map of the X chromosome from telomere to telomere, based primarily on YACs formatted with probes and STSs, is increasingly close to reality. At the Fifth International X Chromosome Workshop, organized by A.M. Poustka and D. Schlessinger in Heidelberg, Germany, April 24--27, 1994, substantial progress was recorded on extension and refinement of the physical map, on the integration of genetic and cytogenetic data, on attempts to use the map to direct gene searches, and on nascent large-scale sequencing efforts. This report summarizes physical and genetic mapping information presented at the workshop and/or published since the reports of the fourth International X Chromosome Workshop. The principle aim of the workshop was to derive a consensus map of the chromosome, in terms of physical contigs emphasizing the location of genes and microsatellite markers. The resulting map is presented and updates previous versions. This report also updates the list of highly informative microsatellites. The text highlights the working state of the map, the genes known to reside on the X, and the progress toward integration of various types of data.

  2. International Coordination of Large-Scale Human Induced Pluripotent Stem Cell Initiatives: Wellcome Trust and ISSCR Workshops White Paper

    PubMed Central

    Soares, Filipa A.C.; Sheldon, Michael; Rao, Mahendra; Mummery, Christine; Vallier, Ludovic

    2014-01-01

    There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here. PMID:25496616

  3. Simultaneous BK Polyomavirus (BKPyV)-associated nephropathy and hemorrhagic cystitis after living donor kidney transplantation.

    PubMed

    Helanterä, Ilkka; Hirsch, Hans H; Wernli, Marion; Ortiz, Fernanda; Lempinen, Marko; Räisänen-Sokolowski, Anne; Auvinen, Eeva; Mannonen, Laura; Lautenschlager, Irmeli

    2016-03-01

    BK polyomavirus (BKPyV) commonly reactivates after kidney transplantation, and can cause polyomavirus-associated nephropathy (PyVAN), whereas after allogeneic stem cell transplantation the most frequent manifestation of BKPyV is polyomavirus-associated hemorrhagic cystitis (PyVHC). Despite high-level BKPyV replication in both, the pathogenesis and manifestation of both BKPyV entities appears to differ substantially. We describe an unusual case of simultaneous PyVAN and PyVHC presenting with acute symptoms in a BKPyV-IgG positive recipient eight months after kidney transplantation from a haploidentical living donor, who was BKPyV-IgG negative. Symptoms of cystitis and viremia subsided rapidly after reduction of immunosuppression. PMID:26771744

  4. Identification of a Novel Cetacean Polyomavirus from a Common Dolphin (Delphinus delphis) with Tracheobronchitis

    PubMed Central

    Anthony, Simon J.; St. Leger, Judy A.; Navarrete-Macias, Isamara; Nilson, Erica; Sanchez-Leon, Maria; Liang, Eliza; Seimon, Tracie; Jain, Komal; Karesh, William; Daszak, Peter; Briese, Thomas; Lipkin, W. Ian

    2013-01-01

    A female short-beaked common dolphin calf was found stranded in San Diego, California in October 2010, presenting with multifocal ulcerative lesions in the trachea and bronchi. Viral particles suggestive of polyomavirus were detected by EM, and subsequently confirmed by PCR and sequencing. Full genome sequencing (Ion Torrent) revealed a circular dsDNA genome of 5,159 bp that was shown to form a distinct lineage within the genus Polyomavirus based on phylogenetic analysis of the early and late transcriptomes. Viral infection and distribution in laryngeal mucosa was characterised using in-situ hybridisation, and apoptosis observed in the virus-infected region. These results demonstrate that polyomaviruses can be associated with respiratory disease in cetaceans, and expand our knowledge of their diversity and clinical significance in marine mammals. PMID:23874559

  5. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    SciTech Connect

    Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke; Ito, Hideki; Shimonohara, Nozomi; Tsuji, Takahiro; Nakajima, Noriko; Suzuki, Yoshio; Matsuo, Koma; Nakagawa, Hidemi; Sata, Tetsutaro; Katano, Harutaka

    2010-03-15

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  6. Pathology of goose haemorrhagic polyomavirus infection in goose embryos.

    PubMed

    Bernáth, Sándor; Farsang, Attila; Kovács, Andrea; Nagy, Edith; Dobos-Kovács, Mihály

    2006-02-01

    Goose embryos were infected with goose haemorrhagic polyomavirus (GHPV) onto the chorioallantoic membrane (CAM) in order to examine the effect of GHPV on the embryos and to obtain data on whether embryos could develop into infected, virus-shedding goslings, as well as to present an accurate biological method for virus titration. The reported method of infection could offer a possibility to express the virus titre as the median embryo infective dose (EID(50)). As a special pathological feature of the disease, extensive cerebral haemorrhages were observed, which protruded the skullcap in many cases. Some embryos infected with 10(1.25) or 10(0.25) EID(50)/0.2 ml were able to hatch; however, they were in poor physical condition and died by post-hatching day 4 showing haemorrhagic nephritis and enteritis of geese. Virus shedding was revealed by polymerase chain reaction. The ability of some of the infected goose embryos to hatch may indicate the potency of GHPV to spread vertically, although this needs further study for confirmation.

  7. Polyomavirus associated nephropathy after kidney and pancreas transplantation: case report.

    PubMed

    Gracin, Sonja; Vojtusek, Ivana Kovacević; Vidas, Zeljko; Knotek, Mladen; Skelin, Ika Kardum; Ljubanović, Danica

    2010-06-01

    Polyomavirus virus associated nephropathy (PVAN) is an important cause of graft failure in the renal transplant population. The prevalence of PVAN has increased from 1% to 10% in the past decade, leading to loss of transplanted organ in 30% to 80% of cases. In the absence of specific antiviral drugs, early detection of disease and modification/reduction of immunosuppressive regimen is currently the cornerstone of therapy. In the setting of multiorgan transplantation, like simultaneous pancreas and kidney transplantation (SPKT), diagnosis and therapy of PVAN can be even more challenging problem. We report a first described case of PVAN in patient after SPKT in Croatia. Patient is a 32 years old Caucasian male with type 1 diabetes mellitus and end stage renal failure, diagnosed for PVAN 6 month after SPKT. Patient was treated with reduced immunosuppressive regimen. At 32 month follow up, patient has preserved kidney and pancreas function with estimated glomerular filtration (eGFR) rate of 91 mL/min and no signs of PVAN on his 2 year protocol kidney biopsy.

  8. JC polyomavirus mutants escape antibody-mediated neutralization.

    PubMed

    Ray, Upasana; Cinque, Paola; Gerevini, Simonetta; Longo, Valeria; Lazzarin, Adriano; Schippling, Sven; Martin, Roland; Buck, Christopher B; Pastrana, Diana V

    2015-09-23

    JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing "blind spots" (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed markedly increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML.

  9. Molecular networks involved in the immune control of BK polyomavirus.

    PubMed

    Girmanova, Eva; Brabcova, Irena; Klema, Jiri; Hribova, Petra; Wohlfartova, Mariana; Skibova, Jelena; Viklicky, Ondrej

    2012-01-01

    BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%-80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%-10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n = 11), infected asymptomatic patients (n = 9), and patients with BK virus nephropathy (n = 10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P < 0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P < 0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.

  10. Building the Human Vaccines Project: strategic management recommendations and summary report of the 15-16 July 2014 business workshop.

    PubMed

    Schenkelberg, Theodore; Kieny, Marie-Paule; Bianco, A E; Koff, Wayne C

    2015-05-01

    The Human Vaccines Project is a bold new initiative, with the goal of solving the principal scientific problem impeding vaccine development for infectious diseases and cancers: the generation of specific, broad, potent and durable immune responses in humans. In the July 2014 workshop, 20 leaders from the public and private sectors came together to give input on strategic business issues for the creation of the Human Vaccines Project. Participants recommended the Project to be established as a nonprofit public-private partnership, structured as a global R&D consortium closely engaged with industrial partners, and located/affiliated with one or more major academic centers conducting vaccine R&D. If successful, participants concluded that the Project could greatly accelerate the development of new and improved vaccines, with the potential to transform disease prevention in the 21st century.

  11. Building the Human Vaccines Project: strategic management recommendations and summary report of the 15-16 July 2014 business workshop.

    PubMed

    Schenkelberg, Theodore; Kieny, Marie-Paule; Bianco, A E; Koff, Wayne C

    2015-05-01

    The Human Vaccines Project is a bold new initiative, with the goal of solving the principal scientific problem impeding vaccine development for infectious diseases and cancers: the generation of specific, broad, potent and durable immune responses in humans. In the July 2014 workshop, 20 leaders from the public and private sectors came together to give input on strategic business issues for the creation of the Human Vaccines Project. Participants recommended the Project to be established as a nonprofit public-private partnership, structured as a global R&D consortium closely engaged with industrial partners, and located/affiliated with one or more major academic centers conducting vaccine R&D. If successful, participants concluded that the Project could greatly accelerate the development of new and improved vaccines, with the potential to transform disease prevention in the 21st century. PMID:25673514

  12. CONCLUSIONS AND RECOMMENDATIONS OF THE EXPERT PANEL: TECHNICAL WORKSHOP ON HUMAN MILK SURVEILLANCE AND BIOMONITORING FOR ENVIRONMENTAL CHEMICALS IN THE UNITED STATES

    EPA Science Inventory

    The Technical Workshop focused on questions related to interpretation of information gathered from human milk biomonitoring studies. Biomonitoring can measure a person’s exposure to a chemical in his/her tissue. Human milk is a unique biological matrix for biomonitoring because i...

  13. Polyomavirus nephropathy - recent pathological diagnostic problems and the report from the 2011 Banff meeting.

    PubMed

    Nishi, Shinichi

    2012-07-01

    Polyomavirus nephropathy (PVN) is a cause of renal allograft dysfunction. Early detection of pathological abnormalities is not easy even in cases with urine decoy cells or polyomavirus viremia. A pathological classification for PVN was proposed by the Banff PVN working group, although the availability of the proposed schema has not been extensively evaluated in the clinical field. At the Banff meeting in 2011, the PVN working group reported the results of the evaluation on interobserver reproducibility and a clinicopathological study of PVN stages and renal outcome. Fair or good reproducibility was noted, although the PVN classification required further modification. PMID:22747469

  14. Risk of squamous cell skin cancer after organ transplant associated with antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2) variants.

    PubMed

    Madeleine, Margaret M; Carter, Joseph J; Johnson, Lisa G; Wipf, Gregory C; Davis, Connie; Berg, Daniel; Nelson, Karen; Daling, Janet R; Schwartz, Stephen M; Galloway, Denise A

    2014-10-01

    Squamous cell skin cancer (SCSC) disproportionately affects organ transplant recipients, and may be related to increased viral replication in the setting of immune suppression. We conducted a nested case-control study among transplant recipients to determine whether SCSC is associated with antibodies to cutaneous human papillomaviruses (HPV), to genes associated with a rare genetic susceptibility to HPV (TMC6/TMC8), or to human polyomaviruses (HPyV). Cases (n = 149) had histologically confirmed SCSC, and controls (n = 290) were individually matched to cases on time since transplant, type of transplant, gender, and race. All subjects had serum drawn immediately prior to transplant surgery. Antibodies to 25 cutaneous HPVs and six HPyVs were assayed by detection of binding to virus-like particles, and 11 TMC6/8 variants were genotyped. After correction for multiple comparisons, only antibodies to HPV37 were associated with SCSC (OR 2.0, 95% CI 1.2-3.4). Common genetic variants of TMC6/8 were not associated with SCSC, but three variants in TMC8 (rs12452890, rs412611, and rs7208422) were associated with greater seropositivity for species 2 betapapillomaviruses among controls. This study suggests that some betaHPVs, but not polyomaviruses, may play a role in the excess risk of SCSC among transplant recipients.

  15. Avian Polyomavirus Genome Sequences Recovered from Parrots in Captive Breeding Facilities in Poland

    PubMed Central

    Dayaram, Anisha; Piasecki, Tomasz; Chrząstek, Klaudia; White, Robyn; Julian, Laurel; van Bysterveldt, Katherine

    2015-01-01

    Eight genomes of avian polyomaviruses (APVs) were recovered and sequenced from deceased Psittacula eupatria, Psittacula krameri, and Melopsittacus undulatus from various breeding facilities in Poland. Of these APV-positive samples, six had previously tested positive for beak and feather disease virus (BFDV) and/or parrot hepatitis B virus (PHBV). PMID:26404592

  16. Avian Polyomavirus Genome Sequences Recovered from Parrots in Captive Breeding Facilities in Poland.

    PubMed

    Dayaram, Anisha; Piasecki, Tomasz; Chrząstek, Klaudia; White, Robyn; Julian, Laurel; van Bysterveldt, Katherine; Varsani, Arvind

    2015-01-01

    Eight genomes of avian polyomaviruses (APVs) were recovered and sequenced from deceased Psittacula eupatria, Psittacula krameri, and Melopsittacus undulatus from various breeding facilities in Poland. Of these APV-positive samples, six had previously tested positive for beak and feather disease virus (BFDV) and/or parrot hepatitis B virus (PHBV). PMID:26404592

  17. DOE Human Genome Program: Contractor-Grantee Workshop IV, November 13--17, 1994, Santa Fe, New Mexico

    SciTech Connect

    Not Available

    1994-10-01

    This volume contains the proceedings of the fourth Contractor-Grantee Workshop for the Department of Energy (DOE) Human Genome Program. Of the 204 abstracts in this book, some 200 describe the genome research of DOE-funded grantees and contractors located at the multidisciplinary centers at Lawrence Berkeley Laboratory, Lawrence Livermore National Laboratory, and Los Alamos National Laboratory; other DOE-supported laboratories; and more than 54 universities, research organizations, and companies in the United States and abroad. Included are 16 abstracts from ongoing projects in the Ethical, Legal, and Social Issues (ELSI) component, an area that continues to attract considerable attention from a wide variety of interested parties. Three abstracts summarize work in the new Microbial Genome Initiative launched this year by the Office of Health and Environmental Research (OHER) to provide genome sequence and mapping data on industrially important microorganisms and those that live under extreme conditions. Many of the projects will be discussed at plenary sessions held throughout the workshop, and all are represented in the poster sessions.

  18. Bottlenecks in deriving definitive hematopoietic stem cells from human pluripotent stem cells: a CIRM mini-symposium and workshop report.

    PubMed

    Shepard, Kelly A; Talib, Sohel

    2014-07-01

    On August 29, 2013, the California Institute for Regenerative Medicine (CIRM) convened a small group of investigators in San Francisco, CA, to discuss a longstanding challenge in the stem cell field: the inability to derive fully functional, definitive hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs). To date, PSC-derived HSCs have been deficient in their developmental potential and their ability to self-renew and engraft upon transplantation. Tasked with identifying key challenges to overcoming this "HSC bottleneck", workshop participants identified critical knowledge gaps in two key areas: (a) understanding the ontogeny of human HSCs, and (b) understanding of the intrinsic and extrinsic factors that govern HSC behavior and function. They agreed that development of new methods and tools is critical for addressing these knowledge gaps. These include molecular profiling of key HSC properties, development of new model systems/assays for predicting and assessing HSC function, and novel technological advancements for manipulating cell culture conditions and genetic programs. The workshop produced tangible advances, including providing a current definition of the nature and challenge of the HSC bottleneck and identifying key mechanistic studies of HSC biology that should be prioritized for future funding initiatives (e.g., including higher risk approaches that have potential for high gain).

  19. BK virus infection activates the TNFα/TNF receptor system in Polyomavirus-associated nephropathy.

    PubMed

    Ribeiro, Andrea; Merkle, Monika; Motamedi, Nasim; Nitschko, Hans; Köppel, Simone; Wörnle, Markus

    2016-01-01

    Polyomavirus-associated nephropathy due to BK virus infection (BKVAN) is recognized as an important cause of significant kidney transplant dysfunction often leading to renal graft loss. The activation of innate immune defense mechanisms during BKVAN is still poorly understood and an altered regulation of inflammatory mediators by resident kidney cells upon viral infection can be expected to contribute to the onset and progression of disease. TNFα interacting with its receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), is largely accepted to be involved in viral responses, exhibiting both proinflammatory and immunosuppressive effects. Our aim was to examine the expressions of TNFα and TNFR1 and 2 in human collecting duct epithelial cells (HCDC) after infection with BKV as well as to study the effect of TNFα and poly(I:C), a synthetic analog of viral RNA, on the expressions of TNF receptors and proinflammatory cytokines and chemokines in HCDC. Quantitative RT-PCR analyses showed a downregulation of TNFα and an upregulation of both TNFR1 and 2 upon exposure of HCDC to the BK virus. TNFα stimulation induced the expressions of IL-6, IL-8, RANTES, and TNFR2. Poly(I:C) upregulated the expressions of both TNFR1 and TNFR2, a response that could be effectively blocked by siRNA to TLR3 and RIG-I, two double-stranded (ds) RNA receptors of the innate immune system. Poly(I:C)-dependent expression of TNFR2 but not TNFR1 was enhanced by TNFα. Taken together, our results suggest an involvement of TNF/TNFR system in virus-associated nephropathy.

  20. Dialogue with Asia's Rural Man. A Report of the Development of Human Resources in Rural Asia Workshop (DHRRAW) (Swanganivas, Thailand, August 4-25, 1974).

    ERIC Educational Resources Information Center

    Ledesma, Antonio L., Comp.; And Others

    General objective of the workshop was to provide a forum for Asian rural leaders in which they could discern the significance and implication of crucial processes by which human potentialities are harnessed for the integral growth of rural peoples and communities. The central question addressed was how to combine economic growth with social…

  1. 78 FR 33849 - Battery-Powered Medical Devices Workshop: Challenges and Opportunities; Public Workshop; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ... HUMAN SERVICES Food and Drug Administration Battery-Powered Medical Devices Workshop: Challenges and... following public workshop entitled ``Battery-Powered Medical Devices Workshop: Challenges and Opportunities''. The purpose of this workshop is to create awareness of the challenges related to...

  2. Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan

    PubMed Central

    2014-01-01

    Background A challenge in human genome research is how to describe the populations being studied. The use of improper and/or imprecise terms has the potential to both generate and reinforce prejudices and to diminish the clinical value of the research. The issue of population descriptors has not attracted enough academic attention outside North America and Europe. In January 2012, we held a two-day workshop, the first of its kind in Japan, to engage in interdisciplinary dialogue between scholars in the humanities, social sciences, medical sciences, and genetics to begin an ongoing discussion of the social and ethical issues associated with population descriptors. Discussion Through the interdisciplinary dialogue, we confirmed that the issue of race, ethnicity and genetic research has not been extensively discussed in certain Asian communities and other regions. We have found, for example, the continued use of the problematic term, “Mongoloid” or continental terms such as “European,” “African,” and “Asian,” as population descriptors in genetic studies. We, therefore, introduce guidelines for reporting human genetic studies aimed at scientists and researchers in these regions. Conclusion We need to anticipate the various potential social and ethical problems entailed in population descriptors. Scientists have a social responsibility to convey their research findings outside of their communities as accurately as possible, and to consider how the public may perceive and respond to the descriptors that appear in research papers and media articles. PMID:24758583

  3. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

    PubMed Central

    2012-01-01

    Background Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset of HPV

  4. Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States.

    PubMed

    Dela Cruz, Florante N; Giannitti, Federico; Li, Linlin; Woods, Leslie W; Del Valle, Luis; Delwart, Eric; Pesavento, Patricia A

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.

  5. Common features of polyomavirus mutants selected on PCC4 embryonal carcinoma cells.

    PubMed Central

    Melin, F; Pinon, H; Reiss, C; Kress, C; Montreau, N; Blangy, D

    1985-01-01

    The genomic rearrangements of six polyomavirus mutants selected on PCC4 embryonal carcinoma cells have been compared and their common characteristics pointed out. All mutants show a duplication which includes at least the adenovirus type 5 (Ad5) E1A-like enhancer core sequence plus a deletion of variable size and location. The presence of the second enhancer core sequence, the SV40-like enhancer, is not required for expression of the PyEC PCC4 phenotype. Two of these mutants are also able to express polyomavirus T antigen on F9 and LT1 cells. Multiadaptation seems to require the duplication of the Ad5 E1A-like core sequence, the maintenance of the SV40-like core sequence and a local change in DNA stability. PMID:2992943

  6. Novel Polyomavirus associated with Brain Tumors in Free-Ranging Raccoons, Western United States

    PubMed Central

    Dela Cruz, Florante N.; Giannitti, Federico; Li, Linlin; Woods, Leslie W.; Del Valle, Luis; Delwart, Eric

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010–May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons. PMID:23260029

  7. Safety and efficacy of an inactivated Carbopol-adjuvanted goose haemorrhagic polyomavirus vaccine for domestic geese.

    PubMed

    Gelfi, Jacqueline; Pappalardo, Michael; Claverys, Carine; Peralta, Brigitte; Guerin, Jean-Luc

    2010-04-01

    Haemorrhagic nephritis enteritis of the goose (HNEG) is an epizootic viral disease in domestic geese. The causal agent is a polyomavirus, namely goose haemorrhagic polyomavirus. To help control the disease, an inactivated vaccine was developed, based on viral particles produced in goose kidney cells. Viral material was quantified using real-time quantitative polymerase chain reaction, inactivated with beta-propiolactone and adjuvanted with Carbopol, an acrylic acid polymer. Carbopol proved to be more immunogenic than aluminium hydroxide and was totally safe when administered to young goslings and breeders alike. Carbopol-adjuvanted vaccine induced a high serological response. Moreover, goslings hatched from vaccinated breeders were protected against viral challenge, indicating that maternally-derived neutralizing antibodies (MDA) were efficiently transferred. MDA were still detectable 15 days post-hatch. Clinical trials will be necessary to accurately evaluate a vaccine-based HNEG control strategy under field conditions.

  8. Small and middle T antigens contribute to lytic and abortive polyomavirus infection

    SciTech Connect

    Tuerler, H.; Salomon, C.

    1985-02-01

    Using three different polyomavirus hr-t mutants and two polyomavirus mlT mutants, the authors studied induction of S-phase by mutants and wild-type virus in quiescent mouse kidney cells, mouse 3T6 cells, and FR 3T3 cells. At different times after infection, they measured the proportion of T-antigen-positive cells, the incorporation of (/sup 3/H)thymidine, the proportion of DNA-synthesizing cells, and the increase in total DNA, RNA, and protein content of the cultures. In permissive mouse cells, they also determined the amount of viral DNA and the proportion of viral capsid-producing cells. In polyomavirus hr-t mutant-infected cultures, the onset of host DNA replication was delayed by several hours, and a smaller proportion of T-antigen-positive cells entered S-phase than in wild-type-infected cultures. Of the two polyomavirus mlT mutants studied, dl-23 behaved similarly to wild-type virus in many, but not all, parameters tested. The poorly replicating but well-transforming mutant dl-8 was able to induce S-phase, and (in permissive cells) progeny virus production, in only about one-third of the T-antigen-positive cells. From the experiments, the authors concluded that mutations affecting small and middle T-antigen cause a reduction in the proportion of cells responding to virus infection and a prolongation of the early phase, i.e., the period before cells center S-phase. In hr-t mutant-infected mouse 3T6 cells, production of viral DNA was <10% of that in wild-type-infected cultures; low hr-t progeny production in 3T6 cells was therefore largely due to poor viral DNA replication.

  9. Polyomavirus large T antigen binds symmetrical repeats at the viral origin in an asymmetrical manner.

    PubMed

    Harrison, Celia; Jiang, Tao; Banerjee, Pubali; Meinke, Gretchen; D'Abramo, Claudia M; Schaffhausen, Brian; Bohm, Andrew

    2013-12-01

    Polyomaviruses have repeating sequences at their origins of replication that bind the origin-binding domain of virus-encoded large T antigen. In murine polyomavirus, the central region of the origin contains four copies (P1 to P4) of the sequence G(A/G)GGC. They are arranged as a pair of inverted repeats with a 2-bp overlap between the repeats at the center. In contrast to simian virus 40 (SV40), where the repeats are nonoverlapping and all four repeats can be simultaneously occupied, the crystal structure of the four central murine polyomavirus sequence repeats in complex with the polyomavirus origin-binding domain reveals that only three of the four repeats (P1, P2, and P4) are occupied. Isothermal titration calorimetry confirms that the stoichiometry is the same in solution as in the crystal structure. Consistent with these results, mutation of the third repeat has little effect on DNA replication in vivo. Thus, the apparent 2-fold symmetry within the DNA repeats is not carried over to the protein-DNA complex. Flanking sequences, such as the AT-rich region, are known to be important for DNA replication. When the orientation of the central region was reversed with respect to these flanking regions, the origin was still able to replicate and the P3 sequence (now located at the P2 position with respect to the flanking regions) was again dispensable. This highlights the critical importance of the precise sequence of the region containing the pentamers in replication.

  10. KI and WU polyomaviruses and CD4+ cell counts in HIV-1-infected patients, Italy.

    PubMed

    Babakir-Mina, Muhammed; Ciccozzi, Massimo; Farchi, Francesca; Bergallo, Massimiliano; Cavallo, Rossana; Adorno, Gaspare; Perno, Carlo Federico; Ciotti, Marco

    2010-09-01

    To investigate an association between KI and WU polyomavirus (KIPyV and WUPyV) infections and CD4+ cell counts, we tested HIV-1-positive patients and blood donors. No association was found between cell counts and virus infections in HIV-1-positive patients. Frequency of KIPyV infection was similar for both groups. WUPyV was more frequent in HIV-1-positive patients.

  11. Cooperation of structural proteins during late events in the life cycle of polyomavirus.

    PubMed Central

    Forstová, J; Krauzewicz, N; Wallace, S; Street, A J; Dilworth, S M; Beard, S; Griffin, B E

    1993-01-01

    The polyomavirus minor late capsid antigen, VP2, is myristylated on its N-terminal glycine, this modification being required for efficient infection of mouse cells. To study further the functions of this antigen, as well as those of the other minor late antigen, VP3, recombinant baculoviruses carrying genes for VP1, VP2, and VP3 have been constructed and the corresponding proteins have been synthesized in insect cells. A monoclonal antibody recognizing VP1, alpha-PyVP1-A, and two monoclonal antibodies against the common region of VP2 and VP3, alpha-PyVP2/3-A and alpha-PyVP2/3-B, have been generated. Reactions of antibodies with antigens were characterized by indirect immunofluorescence, immunoprecipitation, and immunoblot analysis. Immunofluorescent staining of mouse cells infected with polyomavirus showed all antigens to be localized in nuclei. When the late polyomavirus proteins were expressed separately in insect cells, however, only VP1 was efficiently transported into the nucleus; VP2 was localized discretely around the outside of the nucleus, and VP3 exhibited a diffused staining pattern in the cytoplasm. Coexpression of VP2, or VP3, with VP1 restored nuclear localization. Immunoprecipitation of infected mouse cells with either anti-VP1 or anti-VP2/3 antibodies precipitated complexes containing all three species, consistent with the notion that VP1 is necessary for efficient transport of VP2 and VP3 into the nucleus. Purified empty capsid-like particles, formed in nuclei of insect cells coinfected with all three baculoviruses, contained VP2 and VP3 proteins in amounts comparable to those found in empty capsids purified from mouse cells infected with wild-type polyomavirus. Two-dimensional gel analysis of VP1 species revealed that coexpression with VP2 affects posttranslational modification of VP1. Images PMID:8382302

  12. The polyomavirus enhancer activates chromatin accessibility on integration into the HPRT gene.

    PubMed Central

    Pikaart, M; Feng, J; Villeponteau, B

    1992-01-01

    Recent studies suggest that enhancers may increase the accessibility of chromatin to transcription factors. To test the effects of a viral enhancer on chromatin accessibility, we have inserted minigenes with or without the polyomavirus enhancer into the third exon of the hypoxanthine phosphoribosyltransferase (HPRT) gene by homologous recombination and have prepared high-resolution maps of gene accessibility by using a novel polymerase chain reaction assay for DNase I sensitivity. In its native state, we find that the HPRT gene has low sensitivity to DNase I in fibrosarcoma cells. Insertion of the polyomavirus enhancer and neo reporter gene into exon 3 confers altered HPRT DNase I sensitivity for several kilobases on either side of the enhancer. The changes in DNase I sensitivity peak near the enhancer and decline with distance from the enhancer. The increase in HPRT DNase I sensitivity persisted when the tk promoter was deleted from the inserted construct but disappeared when the enhancer was deleted. These experiments identify the polyomavirus enhancer as a cis-acting initiator of chromatin accessibility. Images PMID:1333045

  13. Polyomavirus JC Urinary Shedding in Kidney and Liver Transplant Recipients Associated With Reduced Creatinine Clearance

    PubMed Central

    Kusne, Shimon; Vilchez, Regis A.; Zanwar, Preeti; Quiroz, Jorge; Mazur, Marek J.; Heilman, Raymond L.; Mulligan, David; Butel, Janet S.

    2012-01-01

    Background. Polyomavirus reactivation can cause significant morbidity in solid organ transplant recipients, particularly BK virus (BKV) in kidney transplant patients. Less is known about dynamics of John Cunningham virus (JCV) in nonkidney organ transplant patients. Methods. We examined the frequency of urinary shedding of polyomaviruses BKV and JCV and their relationship to creatinine clearance (CrCl) in a longitudinal study of 41 kidney and 33 liver transplant recipients. Results. Any polyomavirus urinary shedding was more frequent in liver than kidney recipients (64% vs 39%; P = .03). JCV was excreted more frequently by liver than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (69% vs 52%). Mean JCV loads were significantly higher than those of BKV in both patient groups (P < .0001). Lower mean CrCl values were significantly associated with JCV shedding in both kidney and liver recipients (P < .001). Conclusions. These findings suggest that BKV and JCV display different patterns of reactivation and shedding in kidney and liver transplant patients and that JCV may have a role in renal dysfunction in some solid organ transplant recipients. PMID:22802433

  14. Identification of an avian polyomavirus associated with Adélie penguins (Pygoscelis adeliae).

    PubMed

    Varsani, Arvind; Porzig, Elizabeth L; Jennings, Scott; Kraberger, Simona; Farkas, Kata; Julian, Laurel; Massaro, Melanie; Ballard, Grant; Ainley, David G

    2015-04-01

    Little is known about viruses associated with Antarctic animals, although they are probably widespread. We recovered a novel polyomavirus from Adélie penguin (Pygoscelis adeliae) faecal matter sampled in a subcolony at Cape Royds, Ross Island, Antarctica. The 4988 nt Adélie penguin polyomavirus (AdPyV) has a typical polyomavirus genome organization with three ORFs that encoded capsid proteins on the one strand and two non-structural protein-coding ORFs on the complementary strand. The genome of AdPyV shared ~60 % pairwise identity with all avipolyomaviruses. Maximum-likelihood phylogenetic analysis of the large T-antigen (T-Ag) amino acid sequences showed that the T-Ag of AdPyV clustered with those of avipolyomaviruses, sharing between 48 and 52 % identities. Only three viruses associated with Adélie penguins have been identified at a genomic level, avian influenza virus subtype H11N2 from the Antarctic Peninsula and, respectively, Pygoscelis adeliae papillomavirus and AdPyV from capes Crozier and Royds on Ross Island.

  15. Identification of an avian polyomavirus associated with Adélie penguins (Pygoscelis adeliae).

    PubMed

    Varsani, Arvind; Porzig, Elizabeth L; Jennings, Scott; Kraberger, Simona; Farkas, Kata; Julian, Laurel; Massaro, Melanie; Ballard, Grant; Ainley, David G

    2015-04-01

    Little is known about viruses associated with Antarctic animals, although they are probably widespread. We recovered a novel polyomavirus from Adélie penguin (Pygoscelis adeliae) faecal matter sampled in a subcolony at Cape Royds, Ross Island, Antarctica. The 4988 nt Adélie penguin polyomavirus (AdPyV) has a typical polyomavirus genome organization with three ORFs that encoded capsid proteins on the one strand and two non-structural protein-coding ORFs on the complementary strand. The genome of AdPyV shared ~60 % pairwise identity with all avipolyomaviruses. Maximum-likelihood phylogenetic analysis of the large T-antigen (T-Ag) amino acid sequences showed that the T-Ag of AdPyV clustered with those of avipolyomaviruses, sharing between 48 and 52 % identities. Only three viruses associated with Adélie penguins have been identified at a genomic level, avian influenza virus subtype H11N2 from the Antarctic Peninsula and, respectively, Pygoscelis adeliae papillomavirus and AdPyV from capes Crozier and Royds on Ross Island. PMID:25537375

  16. Potential human health effects of acid rain: report of a workshop.

    PubMed

    Goyer, R A; Bachmann, J; Clarkson, T W; Ferris, B G; Graham, J; Mushak, P; Perl, D P; Rall, D P; Schlesinger, R; Sharpe, W

    1985-05-01

    This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time.

  17. Potential human health effects of acid rain: report of a workshop

    PubMed Central

    Goyer, Robert A.; Bachmann, John; Clarkson, Thomas W.; Ferris, Benjamin G.; Graham, Judith; Mushak, Paul; Perl, Daniel P.; Rall, David P.; Schlesinger, Richard; Sharpe, William; Wood, John M.

    1985-01-01

    This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time. PMID:3896772

  18. The KIND Workshop Leader's Guide.

    ERIC Educational Resources Information Center

    Sirch, Willow Ann

    The National Association for Humane and Environmental Education (NAHEE) produces this workshop guide which offers a scripted workshop with handouts for elementary educators interested in sharing curriculum-based activities dedicated to helping young people develop values of kindness and respect toward people, animals, and the Earth. This guide…

  19. Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses.

    PubMed

    Carney, Daniel W; Nelson, Christian D S; Ferris, Bennett D; Stevens, Julia P; Lipovsky, Alex; Kazakov, Teymur; DiMaio, Daniel; Atwood, Walter J; Sello, Jason K

    2014-09-01

    Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry.

  20. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  1. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

    PubMed

    Satyanarayana, G; Marty, F M; Tan, C S

    2014-08-01

    BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.

  2. The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Lednicky, John A.; Keitel, Wendy A.; Poston, David G.; White, Zoe S.; Peng, RongSheng; Liu, Zhensheng; Mehta, Satish K.; Pierson, Duane L.; Rooney, Cliona M.; Vilchez, Regis A.; Smith, E. O'Brian; Butel, Janet S.

    2003-01-01

    Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (P<.03). JCV and BKV virurias were 46.7% and 0%, respectively. JCV shedding was age dependent and occurred commonly in individuals >or=40 years old (P<.03). Seasonal variation was observed in shedding of EBV and JCV, but there was no correlation among shedding of EBV, CMV, and JCV (P>.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

  3. Possible antiviral effect of ciprofloxacin treatment on polyomavirus BK replication and analysis of non-coding control region sequences

    PubMed Central

    2013-01-01

    Acute renal dysfunction (ARD) is a common complication in renal transplant recipients. Multiple factors contribute to ARD development, including acute rejection and microbial infections. Many viral infections after kidney transplantation result from reactivation of “latent” viruses in the host or from the graft, such as the human Polyomavirus BK (BKV). We report the case of a 39 year-old recipient of a 2nd kidney graft who experienced BKV reactivation after a second episode of acute humoral rejection. A 10-day treatment with the quinolone antibiotic ciprofloxacin was administered with an increase of immunosuppressive therapy despite the active BKV replication. Real Time PCR analysis performed after treatment with ciprofloxacin, unexpectedly showed clearance of BK viremia and regression of BK viruria. During the follow-up, BK viremia persisted undetectable while viruria decreased further and disappeared after 3 months. BKV non-coding control region sequence analysis from all positive samples always showed the presence of archetypal sequences, with two single-nucleotide substitutions and one nucleotide deletion that, interestingly, were all representative of the subtype/subgroup I/b-1 we identified by the viral protein 1 sequencing analysis. We report the potential effect of the quinolone antibiotic ciprofloxacin in the decrease of the BKV load in both blood and urine. PMID:24004724

  4. Possible antiviral effect of ciprofloxacin treatment on polyomavirus BK replication and analysis of non-coding control region sequences.

    PubMed

    Umbro, Ilaria; Anzivino, Elena; Tinti, Francesca; Zavatto, Assunta; Bellizzi, Anna; Rodio, Donatella Maria; Mancini, Carlo; Pietropaolo, Valeria; Mitterhofer, Anna Paola

    2013-01-01

    Acute renal dysfunction (ARD) is a common complication in renal transplant recipients. Multiple factors contribute to ARD development, including acute rejection and microbial infections. Many viral infections after kidney transplantation result from reactivation of "latent" viruses in the host or from the graft, such as the human Polyomavirus BK (BKV). We report the case of a 39 year-old recipient of a 2nd kidney graft who experienced BKV reactivation after a second episode of acute humoral rejection. A 10-day treatment with the quinolone antibiotic ciprofloxacin was administered with an increase of immunosuppressive therapy despite the active BKV replication. Real Time PCR analysis performed after treatment with ciprofloxacin, unexpectedly showed clearance of BK viremia and regression of BK viruria. During the follow-up, BK viremia persisted undetectable while viruria decreased further and disappeared after 3 months.BKV non-coding control region sequence analysis from all positive samples always showed the presence of archetypal sequences, with two single-nucleotide substitutions and one nucleotide deletion that, interestingly, were all representative of the subtype/subgroup I/b-1 we identified by the viral protein 1 sequencing analysis.We report the potential effect of the quinolone antibiotic ciprofloxacin in the decrease of the BKV load in both blood and urine.

  5. Possible antiviral effect of ciprofloxacin treatment on polyomavirus BK replication and analysis of non-coding control region sequences.

    PubMed

    Umbro, Ilaria; Anzivino, Elena; Tinti, Francesca; Zavatto, Assunta; Bellizzi, Anna; Rodio, Donatella Maria; Mancini, Carlo; Pietropaolo, Valeria; Mitterhofer, Anna Paola

    2013-01-01

    Acute renal dysfunction (ARD) is a common complication in renal transplant recipients. Multiple factors contribute to ARD development, including acute rejection and microbial infections. Many viral infections after kidney transplantation result from reactivation of "latent" viruses in the host or from the graft, such as the human Polyomavirus BK (BKV). We report the case of a 39 year-old recipient of a 2nd kidney graft who experienced BKV reactivation after a second episode of acute humoral rejection. A 10-day treatment with the quinolone antibiotic ciprofloxacin was administered with an increase of immunosuppressive therapy despite the active BKV replication. Real Time PCR analysis performed after treatment with ciprofloxacin, unexpectedly showed clearance of BK viremia and regression of BK viruria. During the follow-up, BK viremia persisted undetectable while viruria decreased further and disappeared after 3 months.BKV non-coding control region sequence analysis from all positive samples always showed the presence of archetypal sequences, with two single-nucleotide substitutions and one nucleotide deletion that, interestingly, were all representative of the subtype/subgroup I/b-1 we identified by the viral protein 1 sequencing analysis.We report the potential effect of the quinolone antibiotic ciprofloxacin in the decrease of the BKV load in both blood and urine. PMID:24004724

  6. Distinct BK polyomavirus non-coding control region (NCCR) variants in oral fluids of HIV- associated Salivary Gland Disease patients.

    PubMed

    Burger-Calderon, Raquel; Ramsey, Kathy J; Dolittle-Hall, Janet M; Seaman, William T; Jeffers-Francis, Liesl K; Tesfu, Daniel; Nickeleit, Volker; Webster-Cyriaque, Jennifer

    2016-06-01

    HIV-associated Salivary Gland Disease (HIVSGD) is among the most common salivary gland-associated complications in HIV positive individuals and was associated with the small DNA tumorvirus BK polyomavirus (BKPyV). The BKPyV non-coding control region (NCCR) is the main determinant of viral replication and rearranges readily. This study analyzed the BKPyV NCCR architecture and viral loads of 35 immunosuppressed individuals. Throatwash samples from subjects diagnosed with HIVSGD and urine samples from transplant patients were BKPyV positive and yielded BKPyV NCCR sequences. 94.7% of the BKPyV HIVSGD NCCRs carried a rearranged OPQPQQS block arrangement, suggesting a distinct architecture among this sample set. BKPyV from HIV positive individuals without HIVSGD harbored NCCR block sequences that were distinct from OPQPQQS. Cloned HIVSGD BKPyV isolates displayed active promoters and efficient replication capability in human salivary gland cells. The unique HIVSGD NCCR architecture may represent a potentially significant oral-tropic BKPyV substrain.

  7. COINFECTION OF CALIFORNIA SEA LION ADENOVIRUS 1 AND A NOVEL POLYOMAVIRUS IN A HAWAIIAN MONK SEAL (NEOMONACHUS SCHAUINSLANDI).

    PubMed

    Cortés-Hinojosa, Galaxia; Doescher, Bethany; Kinsel, Michael; Lednicky, John; Loeb, Julia; Waltzek, Thomas; Wellehan, James F X

    2016-06-01

    The Hawaiian monk seal (Neomonachus schauinslandi) is an endangered species. Here, we present a clinical case of a 26-yr-old male Hawaiian monk seal (HMS) kept in an aquarium with a history of intermittent anorexia and evidence of renal disease. Histologic examination revealed eosinophilic intranuclear inclusions in the liver. Conventional nested PCR protocols were used to test for viruses, and it tested positive for adenovirus and polyomavirus, and negative for herpesvirus. The adenovirus partial polymerase gene is 100% homologous to that of California sea lion adenovirus 1 (CSLAdV-1). CSLAdV-1 causes viral hepatitis in CSL, and has recently been reported in different species of otariids in an aquarium in Japan ( Otaria flavescens and Arctocephalus pusillus ) and a sequence from Spain has been submitted in NCBI as Otaria flavescens adenovirus-1. The polyomavirus in this animal is a novel virus, and is the first polyomavirus discovered in Hawaiian monk seals. This new virus is designated Hawaiian monk seal polyomavirus (HMSPyV-1), and is 83% homologous to California sea lion Polyomavirus-1 (CSLPyV-1). This is the first report of viral coinfection in a HMS and clinical significance in this case remains unclear but may be associated with advanced age. PMID:27468013

  8. COINFECTION OF CALIFORNIA SEA LION ADENOVIRUS 1 AND A NOVEL POLYOMAVIRUS IN A HAWAIIAN MONK SEAL (NEOMONACHUS SCHAUINSLANDI).

    PubMed

    Cortés-Hinojosa, Galaxia; Doescher, Bethany; Kinsel, Michael; Lednicky, John; Loeb, Julia; Waltzek, Thomas; Wellehan, James F X

    2016-06-01

    The Hawaiian monk seal (Neomonachus schauinslandi) is an endangered species. Here, we present a clinical case of a 26-yr-old male Hawaiian monk seal (HMS) kept in an aquarium with a history of intermittent anorexia and evidence of renal disease. Histologic examination revealed eosinophilic intranuclear inclusions in the liver. Conventional nested PCR protocols were used to test for viruses, and it tested positive for adenovirus and polyomavirus, and negative for herpesvirus. The adenovirus partial polymerase gene is 100% homologous to that of California sea lion adenovirus 1 (CSLAdV-1). CSLAdV-1 causes viral hepatitis in CSL, and has recently been reported in different species of otariids in an aquarium in Japan ( Otaria flavescens and Arctocephalus pusillus ) and a sequence from Spain has been submitted in NCBI as Otaria flavescens adenovirus-1. The polyomavirus in this animal is a novel virus, and is the first polyomavirus discovered in Hawaiian monk seals. This new virus is designated Hawaiian monk seal polyomavirus (HMSPyV-1), and is 83% homologous to California sea lion Polyomavirus-1 (CSLPyV-1). This is the first report of viral coinfection in a HMS and clinical significance in this case remains unclear but may be associated with advanced age.

  9. Chromosome 19 International Workshop

    SciTech Connect

    Pericak-Vance, M.A. . Medical Center); Ropers, H.H. . Dept. of Human Genetics); Carrano, A.J. )

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  10. MAKING SENSE OF HUMAN BIOMONITORING DATA: FINDINGS AND RECOMMENDATIONS OF A WORKSHOP

    EPA Science Inventory

    The ability to measure chemicals in humans (often termed biomonitoring) is far outpacing the ability to reliably interpret these data for public health purposes, creating a major knowledge gap. Until this gap is filled, the great promise of routinely using biomonitoring data to s...

  11. Human-Centred Design Workshops in Collaborative Strategic Design Projects: An Educational and Professional Comparison

    ERIC Educational Resources Information Center

    Liem, Andre; Sanders, Elizabeth B.-N.

    2013-01-01

    It has been found that the implementation of Human-centred Design (HCD) methods in the Fuzzy Front-End is not likely to lead to diversification in educational product planning exercises, where time lines are short and executors lack experience. Companies, interested to collaborate with Master-level Industrial Design students on strategic design…

  12. Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta.

    PubMed

    Simon-Santamaria, Jaione; Rinaldo, Christine Hanssen; Kardas, Piotr; Li, Ruomei; Malovic, Ivana; Elvevold, Kjetil; McCourt, Peter; Smedsrød, Bård; Hirsch, Hans H; Sørensen, Karen Kristine

    2014-01-01

    Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and

  13. Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

    PubMed Central

    Simon-Santamaria, Jaione; Rinaldo, Christine Hanssen; Kardas, Piotr; Li, Ruomei; Malovic, Ivana; Elvevold, Kjetil; McCourt, Peter; Smedsrød, Bård

    2014-01-01

    Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and

  14. The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI.

    PubMed

    Dawes, C; Pedersen, A M L; Villa, A; Ekström, J; Proctor, G B; Vissink, A; Aframian, D; McGowan, R; Aliko, A; Narayana, N; Sia, Y W; Joshi, R K; Jensen, S B; Kerr, A R; Wolff, A

    2015-06-01

    This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food bolus, swallowing and speaking. Saliva provides the fluid in which solid tastants may dissolve and distributes tastants around the mouth to the locations of the taste buds. The hypotonic unstimulated saliva facilitates taste recognition. Salivary amylase is involved in digestion of starches. Saliva acts as a buffer to protect oral, pharyngeal and oesophageal mucosae from orally ingested acid or acid regurgitated from the stomach. Saliva protects the teeth against acid by contributing to the acquired enamel pellicle, which forms a renewable lubricant between opposing tooth surfaces, by being supersaturated with respect to tooth mineral, by containing bicarbonate as a buffer and urea and by facilitating clearance of acidic materials from the mouth. Saliva contains many antibacterial, antiviral and antifungal agents which modulate the oral microbial flora in different ways. Saliva also facilitates the healing of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body.

  15. The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI.

    PubMed

    Dawes, C; Pedersen, A M L; Villa, A; Ekström, J; Proctor, G B; Vissink, A; Aframian, D; McGowan, R; Aliko, A; Narayana, N; Sia, Y W; Joshi, R K; Jensen, S B; Kerr, A R; Wolff, A

    2015-06-01

    This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food bolus, swallowing and speaking. Saliva provides the fluid in which solid tastants may dissolve and distributes tastants around the mouth to the locations of the taste buds. The hypotonic unstimulated saliva facilitates taste recognition. Salivary amylase is involved in digestion of starches. Saliva acts as a buffer to protect oral, pharyngeal and oesophageal mucosae from orally ingested acid or acid regurgitated from the stomach. Saliva protects the teeth against acid by contributing to the acquired enamel pellicle, which forms a renewable lubricant between opposing tooth surfaces, by being supersaturated with respect to tooth mineral, by containing bicarbonate as a buffer and urea and by facilitating clearance of acidic materials from the mouth. Saliva contains many antibacterial, antiviral and antifungal agents which modulate the oral microbial flora in different ways. Saliva also facilitates the healing of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body. PMID:25841068

  16. Mutations in the putative calcium-binding domain of polyomavirus VP1 affect capsid assembly

    NASA Technical Reports Server (NTRS)

    Haynes, J. I. 2nd; Chang, D.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    Calcium ions appear to play a major role in maintaining the structural integrity of the polyomavirus and are likely involved in the processes of viral uncoating and assembly. Previous studies demonstrated that a VP1 fragment extending from Pro-232 to Asp-364 has calcium-binding capabilities. This fragment contains an amino acid stretch from Asp-266 to Glu-277 which is quite similar in sequence to the amino acids that make up the calcium-binding EF hand structures found in many proteins. To assess the contribution of this domain to polyomavirus structural integrity, the effects of mutations in this region were examined by transfecting mutated viral DNA into susceptible cells. Immunofluorescence studies indicated that although viral protein synthesis occurred normally, infective viral progeny were not produced in cells transfected with polyomavirus genomes encoding either a VP1 molecule lacking amino acids Thr-262 through Gly-276 or a VP1 molecule containing a mutation of Asp-266 to Ala. VP1 molecules containing the deletion mutation were unable to bind 45Ca in an in vitro assay. Upon expression in Escherichia coli and purification by immunoaffinity chromatography, wild-type VP1 was isolated as pentameric, capsomere-like structures which could be induced to form capsid-like structures upon addition of CaCl2, consistent with previous studies. However, although VP1 containing the point mutation was isolated as pentamers which were indistinguishable from wild-type VP1 pentamers, addition of CaCl2 did not result in their assembly into capsid-like structures. Immunogold labeling and electron microscopy studies of transfected mammalian cells provided in vivo evidence that a mutation in this region affects the process of viral assembly.

  17. JC polyomavirus nephropathy confirmed by using an in-house polymerase chain reaction method.

    PubMed

    Querido, S; Jorge, C; Sousa, H; Birne, R; Matias, P; Weigert, A; Adragão, T; Bruges, M; Ramos, S; Santos, M; Paixão, P; Curran, M D; Machado, D

    2015-10-01

    We report the case of an isolated JC virus (JCV) infection, without co-infection by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney transplantation. Clinical suspicion followed the observation of a decrease in estimated glomerular filtration rate (eGFR) and a renal allograft biopsy revealing polyomavirus-associated tubulointerstitial nephritis and positivity for SV40. An in-house real-time polymerase chain reaction assay, targeting the presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis. Thirteen months after diagnosis, and following therapeutic measures, eGFR remains stable. PMID:26215933

  18. 75 FR 58411 - Center for Veterinary Medicine eSubmitter Workshop; Public Workshop; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... HUMAN SERVICES Food and Drug Administration Center for Veterinary Medicine eSubmitter Workshop; Public...: ``Center for Veterinary Medicine (CVM) eSubmitter Workshop.'' The purpose of the public workshop is to..., Center for Veterinary Medicine (HFV-100), Food and Drug Administration, 7520 Standish Pl., Rockville,...

  19. Interobserver agreement for Polyomavirus nephropathy grading in renal allografts using the working proposal from the 10th Banff Conference on Allograft Pathology.

    PubMed

    Sar, Aylin; Worawichawong, Suchin; Benediktsson, Hallgrimur; Zhang, Jianguo; Yilmaz, Serdar; Trpkov, Kiril

    2011-12-01

    A classification schema for grading Polyomavirus nephropathy was proposed at the 2009 Banff allograft meeting. The schema included 3 stages of Polyomavirus nephropathy: early (stage A), florid (stage B), and late sclerosing (stage C). Grading categories for histologic viral load levels were also proposed. To examine the applicability and the interobserver agreement of the proposed Polyomavirus nephropathy grading schema, we evaluated 24 renal allograft biopsies with confirmed Polyomavirus nephropathy by histology and SV40. Four renal pathologists independently scored the Polyomavirus nephropathy stage (A, B, or C), without knowledge of the clinical history. Viral load was scored as a percent of tubules exhibiting viral replication, using either a 3-tier viral load score (1: ≤1%; 2: >1%-10%; 3: >10%) or a 4-tier score (1: ≤1%; 2: >1%-≤5%; 3: >5%-15%; 4: >15%). The κ score for the Polyomavirus nephropathy stage was 0.47 (95% confidence interval, 0.35-0.60; P < .001). There was a substantial agreement using both the 3-tier and the 4-tier scoring for the viral load (Kendall concordance coefficients, 0.72 and 0.76, respectively; P < .001 for both). A better complete agreement was found using the 3-tier viral load score. In this first attempt to evaluate the interobserver reproducibility of the proposed Polyomavirus nephropathy classifying schema, we demonstrated moderate κ agreement in assessing the Polyomavirus nephropathy stage and a substantial agreement in scoring the viral load level. The proposed grading schema can be applied in routine allograft biopsy practice for grading the Polyomavirus nephropathy stage and the viral load level. PMID:21733554

  20. Breaking Barriers: A Workshop Series in Human Relations Skills Based Upon Liberated Parents/Liberated Children. (Experimental Edition - Revised).

    ERIC Educational Resources Information Center

    Faber, Adele; Mazlish, Elaine

    This is one of a series of Education for Parenthood manuals developed for use in Salvation Army demonstration programs in parenthood education. This guide presents discussion plans for eight workshop sessions based on the book, "Liberated Parents/Liberated Children." The course was designed to help teenagers (1) become aware of typical negative…

  1. Detection of trichodysplasia spinulosa-associated polyomavirus in a fatal case of myocarditis in a seven-month-old girl.

    PubMed

    Tsuzuki, Shinya; Fukumoto, Hitomi; Mine, Sohtaro; Sato, Noriko; Mochizuki, Makoto; Hasegawa, Hideki; Sekizuka, Tsuyoshi; Kuroda, Makoto; Matsushita, Takeji; Katano, Harutaka

    2014-01-01

    Trichodysplasia spinulosa-associated polyomavirus (TSV) was identified in a seven-month-old girl with myocarditis. The number of TSV genomes detected was higher in the heart than in the other organs. The full-length TSV genome was cloned from the heart. This suggests a possible role of TSV infection in the pathogenesis of myocarditis in infants. PMID:25197415

  2. Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus.

    PubMed

    You, John; O'Hara, Samantha D; Velupillai, Palanivel; Castle, Sherry; Levery, Steven; Garcea, Robert L; Benjamin, Thomas

    2015-10-01

    Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus. PMID:26474471

  3. Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

    PubMed

    Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

    2015-01-01

    Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. PMID:25542476

  4. Anion homeostasis is important for non-lytic release of BK polyomavirus from infected cells

    PubMed Central

    Evans, Gareth L.; Caller, Laura G.; Foster, Victoria; Crump, Colin M.

    2015-01-01

    BK polyomavirus (BKPyV) is a member of a family of potentially oncogenic viruses, whose reactivation can cause severe pathological conditions in transplant patients, leading to graft rejection. As with many non-enveloped viruses, it is assumed that virus release occurs through lysis of the host cell. We now show the first evidence for a non-lytic release pathway for BKPyV and that this pathway can be blocked by the anion channel inhibitor DIDS. Our data show a dose-dependent effect of DIDS on the release of BKPyV virions. We also observed an accumulation of viral capsids in large LAMP-1-positive acidic organelles within the cytoplasm of cells upon DIDS treatment, suggesting potential late endosome or lysosome-related compartments are involved in non-lytic BKPyV release. These data highlight a novel mechanism by which polyomaviruses can be released from infected cells in an active and non-lytic manner, and that anion homeostasis regulation is important in this pathway. PMID:26246492

  5. Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor

    NASA Astrophysics Data System (ADS)

    Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung

    2014-01-01

    In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

  6. [Sequencing and analysis of the complete genome sequence of WU polyomavirus in Fuzhou, China].

    PubMed

    Xiu, Wen-qiong; Shen, Xiao-na; Liu, Guang-hua; Xie, Jian-feng; Kang, Yu-lan; Wang, Mei-ai; Zhang, Wen-qing; Weng, Qi-zhu; Yan, Yan-sheng

    2011-03-01

    WU polyomavirus (WUPyV), a new member of the genus Polyomavirus in the family Polyomaviridae, is recently found in patients with respiratory tract infections. In our study, the complete genome of the two WUPyV isolates (FZ18, FZTF) were sequenced and deposited in GenBank (accession nos. FJ890981, FJ890982). The two sequences of the WUPyV isolates in this study varied little from each other. Compared with other complete genome sequences of WUPyV in GenBank (strain B0, S1-S4, CLFF, accession nos. EF444549, EF444550, EF444551, EF444552, EF444553, EU296475 respectively), the sequence length in nucleotides is 5228bp, 1bp shorter than the known sequences. The deleted base pair was at nucleotide position 4536 in the non-coding region of large T antigen (LTAg). The genome of the WUPyV encoded for five proteins. They were three capsid proteins: VP2, VP1, VP3 and LTAg, small T antigen (STAg), respectively. To investigate whether these nucleotide sequences had any unique features, we compared the genome sequence of the 2 WUPyV isolates in Fuzhou, China to those documented in the GenBank database by using PHYLIP software version 3.65 and the neighbor-joining method. The 2 WUPyV strains in our study were clustered together. Strain FZTF was more closed to the reference strain B0 of Australian than strain FZ18. PMID:21528542

  7. Variable frequency of polyomavirus SV40 and herpesvirus EBV in lymphomas from two different urban population groups in Houston, Texas

    PubMed Central

    Toracchio, Sonia; Kozinetz, Claudia A.; Killen, Deanna E.; Sheehan, Andrea M.; Banez, Eugenio I.; Ittmann, Michael M.; Sroller, Vojtech; Butel, Janet S.

    2009-01-01

    Background Studies have reported differing frequencies of detection of polyomavirus simian virus 40 (SV40) in association with human lymphomas. Objective We addressed the hypothesis that SV40 positivity in lymphomas can vary among sampled populations. Study design Archival paraffin-embedded lymphoma specimens (n=171) from patients at two urban hospitals in Houston, Texas, USA, were analyzed following a cross-sectional study design. Extracted DNAs were characterized by quantitative polymerase chain reaction for the cellular RNase P gene and for SV40 and herpesvirus Epstein-Barr virus (EBV) sequences. Results Patient characteristics of the two study populations differed significantly whereas the classification of tumor types studied did not. SV40 DNA was detected more frequently in lymphomas from the public hospital population (10/44, 23%) than in lymphomas from the veterans’ hospital (VAMC) (4/127, 3%; P < 0.0001). EBV detection in lymphomas also differed between the two groups (17/44, 39% vs. 23/127, 18%; P = 0.01). SV40 positivity was associated with a younger age category of VAMC lymphoma patients (P = 0.02). Expression of T-antigen was detected by immunohistochemistry in half of lymphomas that contained SV40 DNA. Variation was observed in the quality and quantity of DNA recovered from paraffin-embedded specimens, but there was no difference in recoveries of DNA from samples from the two hospitals. Conclusions This study demonstrated that, in a direct comparison, the prevalence of SV40 DNA in lymphomas can differ significantly between groups with different demographic distributions. PMID:19631582

  8. Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model

    PubMed Central

    Geng, Xuehui; Shuda, Yoko; Ostrowski, Stephen M.; Lukianov, Stefan; Jenkins, Frank J.; Honda, Kord; Maricich, Stephen M.; Moore, Patrick S.; Chang, Yuan

    2015-01-01

    Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT and Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting. PMID:26544690

  9. Sequences flanking the pentanucleotide T-antigen binding sites in the polyomavirus core origin help determine selectivity of DNA replication.

    PubMed Central

    Li, L; Li, B L; Hock, M; Wang, E; Folk, W R

    1995-01-01

    Replication of the genomes of the polyomaviruses requires two virus-specified elements, the cis-acting origin of DNA replication, with its auxiliary DNA elements, and the trans-acting viral large tumor antigen (T antigen). Appropriate interactions between them initiate the assembly of a replication complex which, together with cellular proteins, is responsible for primer synthesis and DNA chain elongation. The organization of cis-acting elements within the origins of the polyomaviruses which replicate in mammalian cells is conserved; however, these origins are sufficiently distinct that the T antigen of one virus may function inefficiently or not at all to initiate replication at the origin of another virus. We have studied the basis for such replication selectivity between the murine polyomavirus T antigen and the primate lymphotropic polyomavirus origin. The murine polyomavirus T antigen is capable of carrying out the early steps of the assembly of an initiation complex at the lymphotropic papovavirus origin, including binding to and deformation of origin sequences in vitro. However, the T antigen inefficiently unwinds the origin, and unwinding is influenced by sequences flanking the T antigen pentanucleotide binding sites on the late side of the viral core origin. These same sequences contribute to the replication selectivity observed in vivo and in vitro, suggesting that the inefficient unwinding is the cause of the replication defect. These observations suggest a mechanism by which origins of DNA replication can evolve replication selectivity and by which the function of diverse cellular origins might be temporally activated during the S phase of the eukaryotic cell cycle. PMID:7494263

  10. Women's Workshop.

    ERIC Educational Resources Information Center

    Karelius, Karen

    The Women's Workshop Notebook is the tool used in the nine-week course designed for the mature woman returning to school at Antelope Valley College. The notebook exercises along with the group interaction and instruction stress the importance of personal assessment of strengths, weaknesses, dreams, deliberations and life history in…

  11. Wordland Workshop.

    ERIC Educational Resources Information Center

    Perlish, Harvey Neil

    Can and should the preschool child learn to read? To answer this and related questions, a study was conducted to determine the effectiveness of a television program and parental home assistance in teaching reading skills to three-year-old children. For five days a week over a 39-week period, an experimental group watched "Wordland Workshop," a…

  12. Winter Workshop.

    ERIC Educational Resources Information Center

    Council of Outdoor Educators of Quebec, Montreal.

    Materials on 11 topics presented at a winter workshop for Quebec outdoor educators have been compiled into this booklet. Action story, instant replay, shoe factory, sound and action, and find an object to fit the description are described and recommended as group dynamic activities. Directions for five games (Superlative Selection; Data…

  13. 77 FR 43827 - International Workshop on Alternative Methods for Leptospira

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... HUMAN SERVICES International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing... for the Evaluation of Alternative Toxicological Methods (NICEATM) announces an ``International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the...

  14. Tiny T antigen: an autonomous polyomavirus T antigen amino-terminal domain.

    PubMed Central

    Riley, M I; Yoo, W; Mda, N Y; Folk, W R

    1997-01-01

    Three mRNAs from the murine polyomavirus early region encode the three well-characterized tumor antigens. We report the existence of a fourth alternatively spliced mRNA which encodes a fourth tumor antigen, tiny T antigen, which comprises the amino-terminal domain common to all of the T antigens but is extended by six unique amino acid residues. The amount of tiny T antigen in infected cells is small because of its short half-life. Tiny T antigen stimulates the ATPase activity of Hsc70, most likely because of its DnaJ-like motif. The common amino-terminal domain may interface with chaperone complexes to assist the T antigens in carrying out their diverse functions of replication, transcription, and transformation in the appropriate cellular compartments. PMID:9223500

  15. Identification of amino acid sequences in the polyomavirus capsid proteins that serve as nuclear localization signals

    NASA Technical Reports Server (NTRS)

    Chang, D.; Haynes, J. I. Jr; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    The molecular mechanism participating in the transport of newly synthesized proteins from the cytoplasm to the nucleus in mammalian cells is poorly understood. Recently, the nuclear localization signal sequences (NLS) of many nuclear proteins have been identified, and most have been found to be composed of a highly basic amino acid stretch. A genetic "subtractive" and a biochemical "additive" approach were used in our studies to identify the NLS's of the polyomavirus structural capsid proteins. An NLS was identified at the N-terminus (Ala1-Pro-Lys-Arg-Lys-Ser-Gly-Val-Ser-Lys-Cys11) of the major capsid protein VP1 and at the C-terminus (Glu307 -Glu-Asp-Gly-Pro-Glu-Lys-Lys-Lys-Arg-Arg-Leu318) of the VP2/VP3 minor capsid proteins.

  16. Infectious Offspring: How Birds Acquire and Transmit an Avian Polyomavirus in the Wild

    PubMed Central

    Potti, Jaime; Blanco, Guillermo; Lemus, Jesús Á.; Canal, David

    2007-01-01

    Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an ‘upwards vertical’ route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care. PMID:18060070

  17. Goose Hemorrhagic polyomavirus detection in geese using real-time PCR assay.

    PubMed

    Leon, Olivier; Corrand, Léni; Bich, Tran Ngoc; Le Minor, Odile; Lemaire, Mylène; Guérin, Jean-Luc

    2013-12-01

    Goose hemorrhagic polyomavirus (GHPV) is the viral agent of hemorrhagic nephritis enteritis of geese (HNEG), a lethal disease of goslings. Although death is the most common outcome, geese that recover from HNEG are persistently infected. Here, we present the development of real-time SYBR Green real-time PCR targeted to GHPV and its use to assess the prevalence of GHPV infection in French geese flocks. When compared with classical end-point PCR, real-time PCR revealed a much better sensitivity and equivalent specificity. Real-time PCR could, therefore, be considered a gold standard for the detection of GHPV. Results of field investigations evidenced a very high prevalence of GHPV infections in French geese, largely associated with healthy carriage.

  18. Identification of a nuclear localization sequence in the polyomavirus capsid protein VP2

    NASA Technical Reports Server (NTRS)

    Chang, D.; Haynes, J. I. 2nd; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    A nuclear localization signal (NLS) has been identified in the C-terminal (Glu307-Glu-Asp-Gly-Pro-Gln-Lys-Lys-Lys-Arg-Arg-Leu318) amino acid sequence of the polyomavirus minor capsid protein VP2. The importance of this amino acid sequence for nuclear transport of newly synthesized VP2 was demonstrated by a genetic "subtractive" study using the constructs pSG5VP2 (expressing full-length VP2) and pSG5 delta 3VP2 (expressing truncated VP2, lacking amino acids Glu307-Leu318). These constructs were transfected into COS-7 cells, and the intracellular localization of the VP2 protein was determined by indirect immunofluorescence. These studies revealed that the full-length VP2 was localized in the nucleus, while the truncated VP2 protein was localized in the cytoplasm and not transported to the nucleus. A biochemical "additive" approach was also used to determine whether this sequence could target nonnuclear proteins to the nucleus. A synthetic peptide identical to VP2 amino acids Glu307-Leu318 was cross-linked to the nonnuclear proteins bovine serum albumin (BSA) or immunoglobulin G (IgG). The conjugates were then labeled with fluorescein isothiocyanate and microinjected into the cytoplasm of NIH 3T6 cells. Both conjugates localized in the nucleus of the microinjected cells, whereas unconjugated BSA and IgG remained in the cytoplasm. Taken together, these genetic subtractive and biochemical additive approaches have identified the C-terminal sequence of polyoma-virus VP2 (containing amino acids Glu307-Leu318) as the NLS of this protein.

  19. Human health risk assessment based on trace metals in suspended air particulates, surface dust, and floor dust from e-waste recycling workshops in Hong Kong, China.

    PubMed

    Lau, Winifred Ka Yan; Liang, Peng; Man, Yu Bon; Chung, Shan Shan; Wong, Ming Hung

    2014-03-01

    This study investigated health risks exerted on electronic waste (e-waste) recycling workers exposed to cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), mercury (Hg), and zinc (Zn) in Hong Kong. E-waste recycling workshops were classified into eight working areas: 1 = office, 2 = repair, 3 = dismantling, 4 = storage, 5 = desoldering, 6 = loading, 7 = cable shredding, and 8 = chemical waste. The aforementioned metal concentrations were analyzed in suspended air particulates, surface dust and floor dust collected from the above study areas in five workshops. Elevated Pb levels were measured in dismantling and desoldering areas (582 and 486 μg/100 cm(2) in surface and 3,610 and 19,172 mg/kg in floor dust, respectively). Blood lead levels of 10 and 39.5 μg/dl were estimated using United States Environmental Protection Agency's Adult Lead Model as a result of exposure to the floor dust from these two areas. Human health risk assessments were conducted to evaluate cancer and noncancer risks resulting from exposure to floor dust through the combined pathways of ingestion, dermal contact, and inhalation. Findings indicated that workers may be exposed to cancer risks above the acceptable range at 147 in a million at the 95th percentile in the dismantling area. Workers should be informed of associated risks to safeguard their health. PMID:24288065

  20. Human health risk assessment based on trace metals in suspended air particulates, surface dust, and floor dust from e-waste recycling workshops in Hong Kong, China.

    PubMed

    Lau, Winifred Ka Yan; Liang, Peng; Man, Yu Bon; Chung, Shan Shan; Wong, Ming Hung

    2014-03-01

    This study investigated health risks exerted on electronic waste (e-waste) recycling workers exposed to cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), mercury (Hg), and zinc (Zn) in Hong Kong. E-waste recycling workshops were classified into eight working areas: 1 = office, 2 = repair, 3 = dismantling, 4 = storage, 5 = desoldering, 6 = loading, 7 = cable shredding, and 8 = chemical waste. The aforementioned metal concentrations were analyzed in suspended air particulates, surface dust and floor dust collected from the above study areas in five workshops. Elevated Pb levels were measured in dismantling and desoldering areas (582 and 486 μg/100 cm(2) in surface and 3,610 and 19,172 mg/kg in floor dust, respectively). Blood lead levels of 10 and 39.5 μg/dl were estimated using United States Environmental Protection Agency's Adult Lead Model as a result of exposure to the floor dust from these two areas. Human health risk assessments were conducted to evaluate cancer and noncancer risks resulting from exposure to floor dust through the combined pathways of ingestion, dermal contact, and inhalation. Findings indicated that workers may be exposed to cancer risks above the acceptable range at 147 in a million at the 95th percentile in the dismantling area. Workers should be informed of associated risks to safeguard their health.

  1. The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites.

    PubMed

    Ly, Thai Yen; Walsh, Noreen M; Pasternak, Sylvia

    2012-04-01

    Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with

  2. Creating Fantastic PI Workshops

    SciTech Connect

    Biedermann, Laura B.; Clark, Blythe G.; Colbert, Rachel S.; Dagel, Amber Lynn; Gupta, Vipin P.; Hibbs, Michael R.; Perkins, David Nikolaus; West, Roger Derek

    2015-10-01

    The goal of this SAND report is to provide guidance for other groups hosting workshops and peerto-peer learning events at Sandia. Thus this SAND report provides detail about our team structure, how we brainstormed workshop topics and developed the workshop structure. A Workshop “Nuts and Bolts” section provides our timeline and check-list for workshop activities. The survey section provides examples of the questions we asked and how we adapted the workshop in response to the feedback.

  3. 77 FR 59404 - Food Defense; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-27

    ... HUMAN SERVICES Food and Drug Administration Food Defense; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA), Office... University (OSU), Robert M. Kerr Food & Agricultural Products Center (FAPC), is announcing a public...

  4. 75 FR 21007 - Food Labeling; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ... HUMAN SERVICES Food and Drug Administration Food Labeling; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA), Office... University (OSU), Robert M. Kerr Food & Agricultural Products Center (FAPC), is announcing a public...

  5. KI and WU Polyomaviruses and CD4+ Cell Counts in HIV-1–infected Patients, Italy

    PubMed Central

    Babakir-Mina, Muhammed; Ciccozzi, Massimo; Farchi, Francesca; Bergallo, Massimiliano; Cavallo, Rossana; Adorno, Gaspare; Perno, Carlo Federico

    2010-01-01

    To investigate an association between KI and WU polyomavirus (KIPyV and WUPyV) infections and CD4+ cell counts, we tested HIV-1–positive patients and blood donors. No association was found between cell counts and virus infections in HIV-1–positive patients. Frequency of KIPyV infection was similar for both groups. WUPyV was more frequent in HIV-1–positive patients. PMID:20735940

  6. Silver-enhanced in situ hybridization for detection of polyomavirus DNA in patients with BK virus nephropathy.

    PubMed

    Fritzsche, Florian R; Pianca, Silvio; Gaspert, Ariana; Varga, Zsuzsanna; Wang, Lin; Farrell, Michael P; Chen, Xiao-Bo; Hirsch, Hans H; Springer, Erik; Fehr, Thomas; Myles, Jonathan; Tubbs, Raymond; Moch, Holger

    2011-06-01

    BK virus nephropathy is not an infrequent complication of renal transplantation associated with high rates of graft loss. Although antibodies against SV40 antigen detect different viruses of the polyomavirus family, immunohistochemistry is widely used to confirm the diagnosis of BK virus nephropathy in renal biopsies. Here we aimed to validate the novel silver-enhanced in situ hybridization (SISH) technique for the automated detection of BK virus in renal transplant biopsies. Two different patient cohorts were included. Twenty-nine consecutive patients suspicious for BK virus infection were investigated by SISH and chromogenic in situ hybridization. An additional 26 renal biopsies positive by SV40 immunohistochemistry from 19 patients were analyzed by SISH. Polyomavirus DNA serum levels, as determined by nested PCR analysis, were available for all of these patients. The presence of BK virus DNA in renal tubular cells was identified in 5 of the suspicious cases by both, SISH and chromogenic in situ hybridization . One additional patient was only positive in the SISH. In the second cohort, SISH was positive in all SV40 positive biopsies, but SISH signals were less extensive than SV40 immunohistochemistry. Our results show that the BK virus SISH is an ancillary tool for the detection of polyomavirus DNA in renal biopsies using bright-field microscopy. However, its diagnostic value in comparison with standard immunohistochemistry seems to be limited.

  7. PEA1 and PEA3 enhancer elements are primary components of the polyomavirus late transcription initiator element.

    PubMed Central

    Yoo, W; Martin, M E; Folk, W R

    1991-01-01

    The circular polyomavirus genome is transcribed from divergent promoter regions. Early mRNAs are initiated from a transcription complex formed at a TATA motif, the site of binding of transcription factor TFIID. Early transcription is promoted at a distance by the viral enhancer, which includes DNA motifs bound by cellular proteins of the PEA1 and PEA3 families of transcription activators. In contrast, the predominant viral late mRNAs are initiated within the viral enhancer, which lacks a TATA motif, near the PEA1 and PEA3 DNA motifs. Here, we demonstrate that these PEA1 and PEA3 binding sites are primary components of an autonomous transcription initiator element (Inr). They cause transcription of most polyomavirus late mRNAs and can direct the transcription of heterologous reporter genes. Alternative roles of these DNA motifs as activators of early mRNA transcription and as an initiator element for late mRNA transcription help explain how polyomavirus gene expression is regulated during lytic growth and provides a model for cellular transcription during development. Images PMID:1654447

  8. Temporal and geographic clustering of polyomavirus-associated olfactory tumors in 10 free-ranging raccoons (Procyon lotor).

    PubMed

    Giannitti, F; Higgins, R J; Pesavento, P A; Dela Cruz, F; Clifford, D L; Piazza, M; Parker Struckhoff, A; Del Valle, L; Bollen, A W; Puschner, B; Kerr, E; Gelberg, H; Mete, A; McGraw, S; Woods, L W

    2014-07-01

    Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

  9. 78 FR 12763 - Fecal Microbiota for Transplantation; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... HUMAN SERVICES Food and Drug Administration Fecal Microbiota for Transplantation; Public Workshop AGENCY... ``Fecal Microbiota for Transplantation.'' The purpose of the public workshop is to exchange information... fecal microbiota for transplantation (FMT). ] Date and Time: The public workshop will be held on May...

  10. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    PubMed

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  11. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    PubMed

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  12. Merkel Cell Polyomavirus Small T Antigen Mediates Microtubule Destabilization To Promote Cell Motility and Migration

    PubMed Central

    Knight, Laura M.; Stakaityte, Gabriele; Wood, Jennifer, J.; Abdul-Sada, Hussein; Griffiths, David A.; Howell, Gareth J.; Wheat, Rachel; Blair, G. Eric; Steven, Neil M.; Macdonald, Andrew; Blackbourn, David J.

    2014-01-01

    ABSTRACT Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or replication, to date, no studies have investigated any potential link between MCPyV T antigen expression and the highly metastatic nature of MCC. Here we use a quantitative proteomic approach to show that MCPyV ST promotes differential expression of cellular proteins implicated in microtubule-associated cytoskeletal organization and dynamics. Intriguingly, we demonstrate that MCPyV ST expression promotes microtubule destabilization, leading to a motile and migratory phenotype. We further highlight the essential role of the microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilization and cell motility and implicate the cellular phosphatase catalytic subunit protein phosphatase 4C (PP4C) in the regulation of this process. These findings suggest a possible molecular mechanism for the highly metastatic phenotype associated with MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer with a high metastatic potential. However, the molecular mechanisms leading to virally induced cancer development have yet to be fully elucidated. In particular, no studies have investigated any potential link between the virus and the highly metastatic nature of MCC. We demonstrate that the MCPyV small tumor antigen (ST) promotes the destabilization of the host cell microtubule network, which leads to a more motile and migratory cell phenotype. We further show that MCPyV ST induces this process by regulating the phosphorylation status of the cellular microtubule

  13. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    PubMed

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge.

  14. Analysis of human mini-exome sequencing data from Genetic Analysis Workshop 17 using a Bayesian hierarchical mixture model

    PubMed Central

    2011-01-01

    Next-generation sequencing technologies are rapidly changing the field of genetic epidemiology and enabling exploration of the full allele frequency spectrum underlying complex diseases. Although sequencing technologies have shifted our focus toward rare genetic variants, statistical methods traditionally used in genetic association studies are inadequate for estimating effects of low minor allele frequency variants. Four our study we use the Genetic Analysis Workshop 17 data from 697 unrelated individuals (genotypes for 24,487 autosomal variants from 3,205 genes). We apply a Bayesian hierarchical mixture model to identify genes associated with a simulated binary phenotype using a transformed genotype design matrix weighted by allele frequencies. A Metropolis Hasting algorithm is used to jointly sample each indicator variable and additive genetic effect pair from its conditional posterior distribution, and remaining parameters are sampled by Gibbs sampling. This method identified 58 genes with a posterior probability greater than 0.8 for being associated with the phenotype. One of these 58 genes, PIK3C2B was correctly identified as being associated with affected status based on the simulation process. This project demonstrates the utility of Bayesian hierarchical mixture models using a transformed genotype matrix to detect genes containing rare and common variants associated with a binary phenotype. PMID:22373180

  15. Characterization of heavy metals and brominated flame retardants in the indoor and outdoor dust of e-waste workshops: implication for on-site human exposure.

    PubMed

    Xu, Feng; Liu, Yangcheng; Wang, Junxia; Zhang, Gang; Zhang, Wei; Liu, Lili; Wang, Jinfu; Pan, Bishu; Lin, Kuangfei

    2015-04-01

    Forty-four indoor and outdoor dust samples were collected from e-waste workshops and were analyzed to characterize the heavy metals and brominated flame retardants (BFRs) as well as on-site human exposure. The results showed that the most abundant Polybrominated diphenyl ethers (PBDE) congener from three sites was deca-BDE, and it was penta-BDE for the other site. A significant and positive association was found between BDE-209 and decabromodiphenyl ethane (DBDPE). The high percentage of nona-BDE indicated the debromination of deca-BDE during e-waste recycling. The ratio comparison of BDE-47 to (BDE-100 + BDE-99) indicated that the outdoor dust went through more physiochemical processes. The enrichment factors for Cu and Pb were high in both the indoor and outdoor samples. Cd significantly exceeded the Chinese soil guideline grade III. The PCA results combined with the enrichment factor (EF) values suggested common sources and behaviours of Cu, Pb and Sb in the indoor dust. Co, Cr, Ni, Zn and Mn in the outdoor samples were more likely affected by crust. Strong correlations were found only for Pb and Sb with polybrominated diphenyl ethers (PBDEs). The hazard index for on-site human exposure to Pb was at a chronic risk. Despite the low deleterious risk of BFRs, concern should be given to DBDPE; the chronic toxicity of which is not known.

  16. 77 FR 43846 - Food and Drug Administration Pediatric Medical Devices Workshop; Notice of Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Pediatric Medical Devices... Administration's (FDA) Office of Orphan Products Development is announcing the following workshop: FDA Pediatric Medical Devices Workshop. This meeting is intended to focus on challenges in pediatric device...

  17. 77 FR 14813 - Public Workshop on Minimal Residual Disease; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... HUMAN SERVICES Food and Drug Administration Public Workshop on Minimal Residual Disease; Public Workshop... residual disease (MRD) as a biomarker for evaluating new drugs for the treatment of acute lymphoblastic...., a measurable characteristic that is predictive of disease outcome) that can be used to...

  18. TECHNICAL WORKSHOP ON HUMAN MILK SURVEILLANCE AND RESEARCH ON ENVIRONMENTAL CHEMICALS IN THE U.S.: AN OVERVIEW

    EPA Science Inventory

    Interest in human milk research and monitoring for environmental chemicals is growing, and as studies of chemicals in human milk are initiated, it is of the utmost importance that these studies be conducted using harmonized methods. Due to numerous limitations in previous studies...

  19. Determining the Solar Inactivation Rate of BK Polyomavirus by Molecular Beacon.

    PubMed

    Reano, Dane C; Yates, Marylynn V

    2016-07-01

    The application of molecular beacons (MB) that bind to precise sequences of mRNA provides a near-universal approach in detecting evidence of viral replication. Here, we demonstrate the detection of BK Polyomavirus (BKPyV), an emerging indicator of microbiological water quality, by a quantum dot-based MB. The MB allowed us to rapidly characterize the inactivation rate of BKPyV following exposure to a solar simulator (kobs = 0.578 ± 0.024 h(-1), R(2) = 0.92). Results were validated through a traditional cell-culture assay with immunofluorescence detection (kobs = 0.568 ± 0.011 h(-1), R(2) = 0.97), which exhibited a strong correlation to MB data (R(2) = 0.93). Obtaining solar inactivation rates for BKPyV demonstrates the first use of a MB in characterizing a microbiological inactivation profile and helps assess the appropriateness of adopting BKPyV as an indicator organism for water quality.

  20. Determining the Solar Inactivation Rate of BK Polyomavirus by Molecular Beacon.

    PubMed

    Reano, Dane C; Yates, Marylynn V

    2016-07-01

    The application of molecular beacons (MB) that bind to precise sequences of mRNA provides a near-universal approach in detecting evidence of viral replication. Here, we demonstrate the detection of BK Polyomavirus (BKPyV), an emerging indicator of microbiological water quality, by a quantum dot-based MB. The MB allowed us to rapidly characterize the inactivation rate of BKPyV following exposure to a solar simulator (kobs = 0.578 ± 0.024 h(-1), R(2) = 0.92). Results were validated through a traditional cell-culture assay with immunofluorescence detection (kobs = 0.568 ± 0.011 h(-1), R(2) = 0.97), which exhibited a strong correlation to MB data (R(2) = 0.93). Obtaining solar inactivation rates for BKPyV demonstrates the first use of a MB in characterizing a microbiological inactivation profile and helps assess the appropriateness of adopting BKPyV as an indicator organism for water quality. PMID:27269231

  1. Molecular characterization of avian polyomavirus isolated from psittacine birds based on the whole genome sequence analysis.

    PubMed

    Katoh, Hiroshi; Ohya, Kenji; Une, Yumi; Yamaguchi, Tsuyoshi; Fukushi, Hideto

    2009-07-01

    Seven avian polyomaviruses (APVs) were isolated from seven psittacine birds of four species. Their whole genome sequences were genetically analyzed. Comparing with the sequence of BFDV1 strain, nucleotide substitutions in the sequences of seven APV isolates were found at 63 loci and a high level of conservation of amino acid sequence in each viral protein (VP1, VP2, VP3, VP4, and t/T antigen) was predicted. An A-to-T nucleotide substitution was observed in non-control region of all seven APV sequences in comparison with BFDV1 strain. Two C-to-T nucleotide substitutions were also detected in non-coding regions of one isolate. A phylogenetic analysis of the whole genome sequences indicated that the sequences from the same species of bird were closely related. APV has been reported to have distinct tropism for cell cultures of various avian species. The present study indicated that a single amino acid substitution at position 221 in VP2 was essential for propagating in chicken embryonic fibroblast culture and this substitution was promoted by propagation on budgerigar embryonic fibroblast culture. For two isolates, three serial amino acids appeared to be deleted in VP4. However, this deletion had little effect on virus propagation.

  2. The association between polyomavirus BK strains and BKV viruria in liver transplant recipients

    PubMed Central

    Wang, Robert Y. L.; Li, Yi-Jung; Lee, Wei-Chen; Wu, Hsin-Hsu; Lin, Chan-Yu; Lee, Cheng-Chia; Chen, Yung-Chang; Hung, Cheng-Chieh; Yang, Chih-Wei; Tian, Ya-Chung

    2016-01-01

    BK virus (BKV) is a polyomavirus that cause of allograft dysfunction among kidney transplant recipients. The role of BKV infection in non-renal solid organ transplant recipients is not well understood neither for the relationship between various BKV strains with occurrence of BKV viral viruria. This study aimed to understand the prevalence of BKV infection and identified of BKV various strains in the urine of liver transplant recipients. There was not significant difference of renal outcome between high BKV viruria and low BKV viruria in the liver transplant recipients. The WW-non-coding control region (NCCR) BKV detected in urine was associated with higher urinary BKV load, whereas the Dunlop-NCCR BKV was detected in the urine of low urinary BKV load. An in vitro cultivation system demonstrated that WW-BKV strain exhibiting the higher viral DNA replication efficiency and higher BKV load. Altogether, this is the first study to demonstrate the impact of BKV strains on the occurrence of BK viruria in the liver transplant recipients. PMID:27338010

  3. Evaluation of the Gastrointestinal Tract as Potential Route of Primary Polyomavirus Infection in Mice

    PubMed Central

    Huang, Gang; Zeng, Gang; Huang, Yuchen; Ramaswami, Bala; Randhawa, Parmjeet

    2016-01-01

    Background Detection of Polyomavirus (PyV) DNA in metropolitan rivers worldwide has led to the suggestion that primary viral infection can occur by the oral route. The aim of this study was to test this notion experimentally. Methods Mouse PyV (MPyV) was used to infect C57BL/6J mice by the nasal or intragastric route. Viral load kinetics was studied 3, 7, 10, 14, 21 and 28 days post-infection (dpi) using quantitative PCR. Results Following nasal infection, MPyV DNA was readily detected in many organs including lung, heart, aorta, colon, and stool with viral loads in the range of 103–106 copies/mg wet weight that peaked 7–10 dpi. Complete viral clearance occurred in the serum and kidney by 28 dpi, while clearance in other organs was partial with a 10–100 fold decrease in viral load. In contrast, following intragastric infection peak detection of PyV was delayed to 21 dpi, and viral loads were up to 3 logs lower. There was no detectable virus in the heart, colon, or stool. Conclusions The intragastric route of MPyV infection is successful, not as efficacious as the respiratory route, and associated with delayed viral dissemination as well as a lower peak MPyV load in individual organs. PMID:26939117

  4. The Distinctive Mutational Spectra of Polyomavirus-Negative Merkel Cell Carcinoma

    PubMed Central

    Verhaegen, Monique Elise; Robinson, Dan R.; Wu, Yi-Mi; Dhanasekaran, Saravana Mohan; Palanisamy, Nallasivam; Siddiqui, Javed; Cao, Xuhong; Su, Fengyun; Wang, Rui; Xiao, Hong; Kunju, Lakshmi P.; Mehra, Rohit; Tomlins, Scott A.; Fullen, Douglas Randall; Bichakjian, Christopher Keram; Johnson, Timothy M.; Dlugosz, Andrzej Antoni; Chinnaiyan, Arul M.

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine tumor. Merkel cell polyomavirus (MCPyV) may contribute to tumorigenesis in a subset of tumors via inhibition of tumor suppressors such as retinoblastoma (RB1) by mutated viral T-antigens, but the molecular pathogenesis of MCPyV-negative MCC is largely unexplored. Through our MI-ONCOSEQ precision oncology study we performed integrative sequencing on two cases of MCPyV-negative MCC, as well as a validation cohort of 14 additional MCC cases (n=16). In addition to previously identified mutations in TP53, RB1, and PIK3CA, we discovered activating mutations of oncogenes including HRAS and loss-of-function mutations in PRUNE2 and NOTCH family genes in MCPyV-negative MCC. MCPyV-negative tumors also displayed high overall mutation burden (10.09 +/− 2.32 mutations per Mb) and were characterized by a prominent UV-signature pattern with C > T transitions comprising 85% of mutations. In contrast, mutation burden was low in MCPyV-positive tumors (0.40 +/− 0.09 mutations per Mb) and lacked a UV signature. These findings suggest a potential ontologic dichotomy in MCC, characterized by either viral-dependent or UV-dependent tumorigenic pathways. PMID:26238782

  5. Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer

    PubMed Central

    Keller, Xavier Etienne; Kardas, Piotr; Acevedo, Claudio; Sais, Giovanni; Poyet, Cédric; Banzola, Irina; Mortezavi, Ashkan; Seifert, Burkhardt; Sulser, Tullio

    2015-01-01

    Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as important inflammatory pathogens in prostate cancer. Here, we evaluated whether the preoperative antibody response to BKPyV large T antigen (LTag) and viral capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in 226 patients undergoing radical prostatectomy for primary prostate cancer. Essentially, the multivariate Cox regression analysis revealed that preoperative seropositivity to BKPyV LTag significantly reduced the risk of biochemical recurrence, independently of established predictors of biochemical recurrence such as tumor stage, Gleason score and surgical margin status. The predictive accuracy of the regression model was denotatively increased by the inclusion of the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine gene expression profile upon assessment of the cellular immune response elicited by LTag. Taken together, our findings suggest that the BKPyV LTag serology may serve as a prognostic factor in prostate cancer. If validated in additional studies, this biomarker may allow for better treatment decisions after radical prostatectomy. Finally, the favorable outcome of LTag seropositive patients may provide a potential opportunity for novel therapeutic approaches targeting a viral antigen. PMID:25749042

  6. Laboratory reporting accuracy of polymerase chain reaction testing for avian polyomavirus.

    PubMed

    Fitzgerald, Brenna; Olsen, Geoff; Speer, Brian

    2013-03-01

    Polymerase chain reaction (PCR) assays are available for detection of birds infected with avian polyomavirus (APV). Several laboratories offer this diagnostic assay in the United States, but little information is available regarding assay sensitivity, specificity, and accuracy. In this study, known APV-positive and APV-negative samples (each n = 10, 5 undiluted and 5 diluted) were sent to 5 commercial laboratories. A significant difference in reporting accuracy was found among laboratories, most notably for dilute APV-positive samples. Two out of 5 laboratories provided 100% accurate results, 1 had an accuracy of 90%, and 2 reported 80% and 75% accuracy, respectively. The accuracies of the last 2 laboratories were negatively affected by test sensitivities of 60% and 50%, respectively. These findings show that although accurate results were reported by most laboratories, both false-positive and false-negative results were reported by at least 3 laboratories, and false-negative results reported for dilute APV-positive samples predominated. These study findings illustrate a need for veterinary diagnostic laboratories to institute improved voluntary quality control measures.

  7. Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression

    PubMed Central

    Bhatia, Kishor; Goedert, James J.; Modali, Rama; Preiss, Liliana; Ayers, Leona W.

    2010-01-01

    Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (P≤0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis, and longer survival (P≤0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV. PMID:19551862

  8. Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

    PubMed Central

    Cioni, M.; Leboeuf, C.; Comoli, P.; Ginevri, F.

    2016-01-01

    Uncontrolled BK polyomavirus (BKPyV) replication in kidney transplant recipients (KTRs) causes polyomavirus‐associated nephropathy and allograft loss. Reducing immunosuppression is associated with clearing viremia and nephropathy and increasing BKPyV‐specific T cell responses in most patients; however, current immunoassays have limited sensitivity, target mostly CD4+ T cells, and largely fail to predict onset and clearance of BKPyV replication. To characterize BKPyV‐specific CD8+ T cells, bioinformatics were used to predict 9mer epitopes in the early viral gene region (EVGR) presented by 14 common HLAs in Europe and North America. Thirty‐nine EVGR epitopes were experimentally confirmed by interferon‐γ enzyme‐linked immunospot assays in at least 30% of BKPyV IgG–seropositive healthy participants. Most 9mers clustered in domains, and some were presented by more than one HLA class I, as typically seen for immunodominant epitopes. Specific T cell binding using MHC class I streptamers was demonstrated for 21 of 39 (54%) epitopes. In a prospective cohort of 118 pediatric KTRs, 19 patients protected or recovering from BKPyV viremia were experimentally tested, and 13 epitopes were validated. Single HLA mismatches were not associated with viremia, suggesting that failing immune control likely involves multiple factors including maintenance immunosuppression. Combining BKPyV load and T cell assays using immunodominant epitopes may help in evaluating risk and reducing immunosuppression and may lead to safe adoptive T cell transfer. PMID:26663765

  9. [Clinical significance of monitoring BK polyomavirus in patients after hematopoietic stem cell transplantation].

    PubMed

    Yin, Chang-Xin; Jiang, Qian-Li; He, Han; Yu, Guo-Pan; Xu, Yue; Meng, Fan-Yi; Yang, Mo

    2012-02-01

    This study was aimed to establish a method for rapid detecting BK polyomavirus (BKV) and to investigate the feasibility and value used in leukemia patients undergoing hematopoietic stem cell transplantation. Primers were designed according to BKV gene sequence; the quantitative standards for BKV and a real-time fluorescent quantitative PCR for BKV were established. The BKV level in urine samples from 36 patients after hematopoietic stem cell transplantation were detected by established method. The results showed that the standard of reconstructed plasmid and real time fluorescent quantitative PCR method were successfully established, its good specificity, sensitivity and stability were confirmed by experiments. BKV was found in 55.56% of urine samples, and the BKV load in urine was 2.46 × 10(4) - 7.8 × 10(9) copy/ml. It is concluded that the establishment of real-time fluorescent quantitative PCR for BKV detection provides a method for early diagnosis of the patients with hemorrhagic cystitis after hematopoietic stem cell transplantation.

  10. BK polyomavirus reactivation after reduced-intensity double umbilical cord blood cell transplantation.

    PubMed

    Satyanarayana, Gowri; Hammond, Sarah P; Broge, Thomas A; Mackenzie, Matthew R; Viscidi, Raphael; Politikos, Ioannis; Koralnik, Igor J; Cutler, Corey S; Ballen, Karen; Boussiotis, Vassiliki; Marty, Francisco M; Tan, Chen Sabrina

    2015-03-01

    Serial serum samples from 27 patients who underwent double umbilical cord blood transplantation (dUCBT) were analyzed for BK polyomavirus (BKPyV) DNA by real-time PCR and BKPyV-specific immune globulin by ELISA. Clinical data were collected on all patients. All pre-transplant sera had detectable anti-BKPyV IgG. Fifteen patients (56%) had detectable serum BKPyV DNA (median 8.9 × 10(4) copies/ml; range 4.1 × 10(3)-7.9 × 10(6) copies/ml) a median of 40 days (range, 27-733 days) after dUCBT, with highest viral loads on Day 100 assessment. The cumulative probability of developing BKPyV viremia by Day 100 was 0.52 (95% CI, 0.33-0.71). Six of 15 patients with BKPyV viremia experienced hemorrhagic cystitis by Day 100. By Day 100, there was a trend towards higher BKPyV viral loads in sera of patients with hemorrhagic cystitis than in those BKPyV viremic patients without hemorrhagic cystitis (p = 0.06). BKPyV viremia was associated with significantly higher anti-BKPyV IgM values at 6 months post-dUCBT (P = 0.003). BKPyV viremia occurs early after dUBCT and is associated with a detectable humoral immune response by 6 months post-dUBCT.

  11. Whole genome sequence of a goose haemorrhagic polyomavirus detected in Hungary.

    PubMed

    Fehér, Enikő; Lengyel, György; Dán, Adám; Farkas, Szilvia L; Bányai, Krisztián

    2014-06-01

    Goose haemorrhagic polyomavirus (GHPV) provoke haemorrhagic nephritis and enteritis of domestic geese. Outbreaks were detected in European countries and caused economic losses for goose keepers. Domestic ducks may be infected with GHPV without any signs typical for geese. The genomic organisation of some isolates was described but the gene functions and the pathomechanisms of the virus was not precisely defined. Here we describe the genome sequence and structure of GHPV of a goose from a Hungarian goose flock showing characteristics of the haemorrhagic nephritis and enteritis. The GHPV genome investigated in this study was 5252 bp long and was very similar (99% nucleotide identity) to sequences deposited in the GenBank. All the whole GHPV genomes possess the same ORFs in length, including the VP1, VP2, VP3, ORF-X, t and T tumour antigens. Amino acid changes are detected mainly in the putative ORF-X region. Data about the GHPV genome imply a conserved genomic structure among isolates from different countries. Genomic and epidemiological studies may help vaccine development efforts and identify potential heterologous reservoirs of GHPV.

  12. NASA/HAA Advanced Rotorcraft Technology and Tilt Rotor Workshops. Volume 4: Flight Control Avionics Systems and Human Factors

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Helicopter user needs, technology requirements and status, and proposed research and development action are summarized. It is divided into three sections: flight dynamics and control; all weather operations; and human factors.

  13. Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer.

    PubMed Central

    Kamachi, Y; Ogawa, E; Asano, M; Ishida, S; Murakami, Y; Satake, M; Ito, Y; Shigesada, K

    1990-01-01

    We have previously identified a protein factor, PEBP2 (polyomavirus enhancer-binding protein), in the nuclear extract from mouse NIH 3T3 cells which binds to the sequence motif, PEA2, located within the polyomavirus enhancer A element. Upon cellular transformation with activated oncogene c-Ha-ras, this factor frequently undergoes drastic molecular modifications into an altered form having a considerably reduced molecular size. In this study, the altered form, PEBP3, was purified to near homogeneity. The purified PEBP3 comprised two sets of families of polypeptides, alpha-1 to alpha-4 and beta-1 to beta-2, which were 30 to 35 kilodaltons and 20 to 25 kilodaltons in size, respectively. Both kinds of polypeptides possessed DNA-binding activities with exactly the same sequence specificity. Individual alpha or beta polypeptides complexed with DNA showed faster gel mobilities than did PEBP3. However, the original gel retardation pattern was restored when alpha and beta polypeptides were mixed together in any arbitrary pair. These observation along with the results of UV- and chemical-cross-linking studies led us to conclude that PEBP3 is a heterodimer of alpha and beta subunits, potentially having a divalent DNA-binding activity. Furthermore, PEBP3 was found to bind a second, hitherto-unnoticed site of the polyomavirus enhancer that is located within the B element and coincides with the sequence previously known as the simian virus 40 enhancer core homology. From comparison of this and the original binding sites, the consensus sequence for PEBP3 was defined to be PuACCPuCA. These findings provided new insights into the biological significance of PEBP3 and PEBP2. Images PMID:2168969

  14. Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer.

    PubMed

    Kamachi, Y; Ogawa, E; Asano, M; Ishida, S; Murakami, Y; Satake, M; Ito, Y; Shigesada, K

    1990-10-01

    We have previously identified a protein factor, PEBP2 (polyomavirus enhancer-binding protein), in the nuclear extract from mouse NIH 3T3 cells which binds to the sequence motif, PEA2, located within the polyomavirus enhancer A element. Upon cellular transformation with activated oncogene c-Ha-ras, this factor frequently undergoes drastic molecular modifications into an altered form having a considerably reduced molecular size. In this study, the altered form, PEBP3, was purified to near homogeneity. The purified PEBP3 comprised two sets of families of polypeptides, alpha-1 to alpha-4 and beta-1 to beta-2, which were 30 to 35 kilodaltons and 20 to 25 kilodaltons in size, respectively. Both kinds of polypeptides possessed DNA-binding activities with exactly the same sequence specificity. Individual alpha or beta polypeptides complexed with DNA showed faster gel mobilities than did PEBP3. However, the original gel retardation pattern was restored when alpha and beta polypeptides were mixed together in any arbitrary pair. These observation along with the results of UV- and chemical-cross-linking studies led us to conclude that PEBP3 is a heterodimer of alpha and beta subunits, potentially having a divalent DNA-binding activity. Furthermore, PEBP3 was found to bind a second, hitherto-unnoticed site of the polyomavirus enhancer that is located within the B element and coincides with the sequence previously known as the simian virus 40 enhancer core homology. From comparison of this and the original binding sites, the consensus sequence for PEBP3 was defined to be PuACCPuCA. These findings provided new insights into the biological significance of PEBP3 and PEBP2. PMID:2168969

  15. Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21.

    PubMed

    Kazem, Siamaque; van der Meijden, Els; Wang, Richard C; Rosenberg, Arlene S; Pope, Elena; Benoit, Taylor; Fleckman, Philip; Feltkamp, Mariet C W

    2014-01-01

    Trichodysplasia spinulosa (TS) is a proliferative skin disease observed in severely immunocompromized patients. It is characterized by papule and trichohyalin-rich spicule formation, epidermal acanthosis and distention of dysmorphic hair follicles overpopulated by inner root sheath cells (IRS). TS probably results from active infection with the TS-associated polyomavirus (TSPyV), as indicated by high viral-load, virus protein expression and particle formation. The underlying pathogenic mechanism imposed by TSPyV infection has not been solved yet. By analogy with other polyomaviruses, such as the Merkel cell polyomavirus associated with Merkel cell carcinoma, we hypothesized that TSPyV T-antigen promotes proliferation of infected IRS cells. Therefore, we analyzed TS biopsy sections for markers of cell proliferation (Ki-67) and cell cycle regulation (p16ink4a, p21waf, pRB, phosphorylated pRB), and the putatively transforming TSPyV early large tumor (LT) antigen. Intense Ki-67 staining was detected especially in the margins of TS hair follicles, which colocalized with TSPyV LT-antigen detection. In this area, staining was also noted for pRB and particularly phosphorylated pRB, as well as p16ink4a and p21waf. Healthy control hair follicles did not or hardly stained for these markers. Trichohyalin was particularly detected in the center of TS follicles that stained negative for Ki-67 and TSPyV LT-antigen. In summary, we provide evidence for clustering of TSPyV LT-antigen-expressing and proliferating cells in the follicle margins that overproduce negative cell cycle regulatory proteins. These data are compatible with a scenario of TSPyV T-antigen-mediated cell cycle progression, potentially creating a pool of proliferating cells that enable viral DNA replication and drive papule and spicule formation.

  16. Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma

    NASA Technical Reports Server (NTRS)

    Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.

    2002-01-01

    Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.

  17. Workshop introduction

    SciTech Connect

    Streeper, Charles

    2010-01-01

    The Department of Energy's National Nuclear Security Administration's Global Threat Reduction Initiative (GTRI) has three subprograms that directly reduce the nuclear/radiological threat; Convert (Highly Enriched Uranium), Protect (Facilities), and Remove (Materials). The primary mission of the Off-Site Source Recovery Project (OSRP) falls under the 'Remove' subset. The purpose of this workshop is to provide a venue for joint-technical collaboration between the OSRP and the Nuclear Radiation Safety Service (NRSS). Eisenhower's Atoms for Peace initiative and the Soviet equivalent both promoted the spread of the paradoxical (peaceful and harmful) properties of the atom. The focus of nonproliferation efforts has been rightly dedicated to fissile materials and the threat they pose. Continued emphasis on radioactive materials must also be encouraged. An unquantifiable threat still exists in the prolific quantity of sealed radioactive sources (sources) spread worldwide. It does not appear that the momentum of the evolution in the numerous beneficial applications of radioactive sources will subside in the near future. Numerous expert studies have demonstrated the potentially devastating economic and psychological impacts of terrorist use of a radiological dispersal or emitting device. The development of such a weapon, from the acquisition of the material to the technical knowledge needed to develop and use it, is straightforward. There are many documented accounts worldwide of accidental and purposeful diversions of radioactive materials from regulatory control. The burden of securing sealed sources often falls upon the source owner, who may not have a disposal pathway once the source reaches the end of its useful life. This disposal problem is exacerbated by some source owners not having the resources to safely and compliantly store them. US Nuclear Regulatory Commission (NRC) data suggests that, in the US alone, there are tens of thousands of high-activity (IAEA

  18. Human polyomavirus JCV late leader peptide region contains important regulatory elements

    SciTech Connect

    Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh |; Khalili, Kamel; Safak, Mahmut . E-mail: msafak@temple.edu

    2006-05-25

    Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader peptide region, indicating the critical importance of these two protected regions in JCV regulation. Altogether, these findings suggest that the late leader peptide region contains important regulatory elements to which transcription factors bind and contribute to the JCV gene regulation and replication.

  19. Mars exploration study workshop 2

    NASA Technical Reports Server (NTRS)

    Duke, Michael B.; Budden, Nancy Ann

    1993-01-01

    A year-long NASA-wide study effort has led to the development of an innovative strategy for the human exploration of Mars. The latest Mars Exploration Study Workshop 2 advanced a design reference mission (DRM) that significantly reduces the perceived high costs, complex infrastructure, and long schedules associated with previous Mars scenarios. This surface-oriented philosophy emphasizes the development of high-leveraging surface technologies in lieu of concentrating exclusively on space transportation technologies and development strategies. As a result of the DRM's balanced approach to mission and crew risk, element commonality, and technology development, human missions to Mars can be accomplished without the need for complex assembly operations in low-Earth orbit. This report, which summarizes the Mars Exploration Study Workshop held at the Ames Research Center on May 24-25, 1993, provides an overview of the status of the Mars Exploration Study, material presented at the workshop, and discussions of open items being addressed by the study team. The workshop assembled three teams of experts to discuss cost, dual-use technology, and international involvement, and to generate a working group white paper addressing these issues. The three position papers which were generated are included in section three of this publication.

  20. Stillbirth Classification—Developing an International Consensus for Research: Executive Summary of a National Institute of Child Health and Human Development Workshop

    PubMed Central

    Reddy, Uma M.; Goldenberg, Robert; Silver, Robert; Smith, Gordon C. S.; Pauli, Richard M.; Wapner, Ronald J.; Gardosi, Jason; Pinar, Halit; Grafe, Marjorie; Kupferminc, Michael; Varli, Ingela Hulthén; Erwich, Jan Jaap H. M.; Fretts, Ruth C.; Willinger, Marian

    2009-01-01

    Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22–24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed. Experts developed evidence-based characteristics of maternal, fetal, and placental conditions to attribute a condition as a cause of stillbirth. These conditions include infection, maternal medical conditions, antiphospholipid syndrome, heritable thrombophilias, red cell alloimmunization, platelet alloimmunization, congenital malformations, chromosomal abnormalities including confined placental mosaicism, fetomaternal hemorrhage, placental and umbilical cord abnormalities including vasa previa and placental abruption, complications of multifetal gestation, and uterine complications. In all cases, owing to lack of sufficient knowledge about disease states and normal development, there will be a degree of uncertainty regarding whether a specific condition was indeed the cause of death. PMID:19888051

  1. Could Workshops Become Obsolete?

    ERIC Educational Resources Information Center

    Riscalla, Louise

    1974-01-01

    The author discusses some of the limitations of the use of sheltered workshops and behavior modification in vocational rehabilitation for the handicapped and promotes the possibility of on-the-job training as an alternative to sheltered workshops. (EA)

  2. IPHE Infrastructure Workshop Proceedings

    SciTech Connect

    2010-02-01

    This proceedings contains information from the IPHE Infrastructure Workshop, a two-day interactive workshop held on February 25-26, 2010, to explore the market implementation needs for hydrogen fueling station development.

  3. Report from the Light Water Reactor Sustainability Workshop on Advanced Instrumentation, Information, and Control Systems and Human-System Interface Technologies

    SciTech Connect

    Bruce P. Hallbert; J. J. Persensky; Carol Smidts; Tunc Aldemir; Joseph Naser

    2009-08-01

    . As an initial step in accomplishing this effort, the Light Water Reactor Sustainability Workshop on Advanced Instrumentation, Information, and Control Systems and Human-System Interface Technologies was held March 20–21, 2009, in Columbus, Ohio, to enable industry stakeholders and researchers in identification of the nuclear industry’s needs in the areas of future I&C technologies and corresponding technology gaps and research capabilities. Approaches for collaboration to bridge or fill the technology gaps were presented and R&D activities and priorities recommended. This report documents the presentations and discussions of the workshop and is intended to serve as a basis for the plan under development to achieve the goals of the I&C research pathway.

  4. GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant human Growth Hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, t...

  5. Designing Effective Workshops. Workshop Resource Manual.

    ERIC Educational Resources Information Center

    Braus, Judy A.; Monroe, Martha C.

    This booklet is one in a series of resource manuals to help teacher educators conduct environmental education (EE) teacher workshops or promote EE programs. This unit offers background information and strategies for designing and leading teacher education workshops and programs and benefits those unfamiliar with adult education methods and…

  6. ICP-MS Workshop

    SciTech Connect

    Carman, April J.; Eiden, Gregory C.

    2014-11-01

    This is a short document that explains the materials that will be transmitted to LLNL and DNN HQ regarding the ICP-MS Workshop held at PNNL June 17-19th. The goal of the information is to pass on to LLNL information regarding the planning and preparations for the Workshop at PNNL in preparation of the SIMS workshop at LLNL.

  7. Thematic Issue: Workshops.

    ERIC Educational Resources Information Center

    Kirby, Michael, Ed.

    1978-01-01

    The articles in this publication trace the historical development of the theatre workshop, explain the relationship between the workshop and experimental theatre, and analyze the ways in which current drama workshops teach and develop the dramatic skills of the participants. The topics discussed include the special skills, production-oriented, and…

  8. Phylogenetic and structural analysis of merkel cell polyomavirus VP1 in Brazilian samples.

    PubMed

    Baez, Camila F; Diaz, Nuria C; Venceslau, Marianna T; Luz, Flávio B; Guimarães, Maria Angelica A M; Zalis, Mariano G; Varella, Rafael B

    2016-08-01

    Our understanding of the phylogenetic and structural characteristics of the Merkel Cell Polyomavirus (MCPyV) is increasing but still scarce, especially in samples originating from South America. In order to investigate the properties of MCPyV circulating in the continent in more detail, MCPyV Viral Protein 1 (VP1) sequences from five basal cell carcinoma (BCC) and four saliva samples from Brazilian individuals were evaluated from the phylogenetic and structural standpoint, along with all complete MCPyV VP1 sequences available at Genbank database so far. The VP1 phylogenetic analysis confirmed the previously reported pattern of geographic distribution of MCPyV genotypes and the complexity of the South-American clade. The nine Brazilian samples were equally distributed in the South-American (3 saliva samples); North American/European (2 BCC and 1 saliva sample); and in the African clades (3 BCC). The classification of mutations according to the functional regions of VP1 protein revealed a differentiated pattern for South-American sequences, with higher number of mutations on the neutralizing epitope loops and lower on the region of C-terminus, responsible for capsid formation, when compared to other continents. In conclusion, the phylogenetic analysis showed that the distribution of Brazilian VP1 sequences agrees with the ethnic composition of the country, indicating that VP1 can be successfully used for MCPyV phylogenetic studies. Finally, the structural analysis suggests that some mutations could have impact on the protein folding, membrane binding or antibody escape, and therefore they should be further studied. PMID:27173789

  9. Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.

    PubMed Central

    Guo, Z S; DePamphilis, M L

    1992-01-01

    The origins of DNA replication (ori) in simian virus 40 (SV40) and polyomavirus (Py) contain an auxiliary component (aux-2) composed of multiple transcription factor binding sites. To determine whether this component stimulated replication by binding specific transcription factors, aux-2 was replaced by synthetic oligonucleotides that bound a single transcription factor. Sp1 and T-antigen (T-ag) sites, which exist in the natural SV40 aux-2 sequence, provided approximately 75 and approximately 20%, respectively, of aux-2 activity when transfected into monkey cells. In cell extracts, only T-ag sites were active. AP1 binding sites could replace completely either SV40 or Py aux-2. Mutations that eliminated AP1 binding also eliminated AP1 stimulation of replication. Yeast GAL4 binding sites that strongly stimulated transcription in the presence of GAL4 proteins failed to stimulate SV40 DNA replication, although they did partially replace Py aux-2. Stimulation required the presence of proteins consisting of the GAL4 DNA binding domain fused to specific activation domains such as VP16 or c-Jun. These data demonstrate a clear role for transcription factors with specific activation domains in activating both SV40 and Py ori. However, no correlation was observed between the ability of specific proteins to stimulate promoter activity and their ability to stimulate origin activity. We propose that only transcription factors whose specific activation domains can interact with the T-ag initiation complex can stimulate SV40 and Py ori-core activity. Images PMID:1317005

  10. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  11. Visual detection of goose haemorrhagic polyomavirus in geese and ducks by loop-mediated isothermal amplification.

    PubMed

    Woźniakowski, Grzegorz; Tarasiuk, Karolina

    2015-01-01

    Goose haemorrhagic polyomavirus (GHPV) is an aetiological agent of haemorrhagic nephritis and enteritis of geese occurring in geese (Anser anser). GHPV may also infect Muscovy ducks (Carina mochata) and mule ducks. Early detection of GHPV is important to isolate the infected birds from the rest of the flock thus limiting infection transmission. The current diagnosis of haemorrhagic nephritis and enteritis of geese is based on virus isolation, histopathological examination, haemagglutination inhibition assay, ELISA and polymerase chain reaction (PCR). Recently, real-time PCR assay was developed which considerably improved detection of GHPV. In spite of many advantages, these methods are still time-consuming and inaccessible for laboratories with limited access to ELISA plate readers or PCR thermocyclers. The aim of our study was to develop loop-mediated isothermal amplification (LAMP) that may be conducted in a water bath. Two pairs of specific primers complementary to VP1 gene of GHPV were designed. The results of GHPV LAMP were recorded under ultraviolet light. Our study showed LAMP was able to specifically amplify VP1 fragment of a GHPV without cross-reactivity with other pathogens of geese and ducks. LAMP detected as little as 1.5 pg of DNA extracted from a GHPV standard strain (150 pg/µl). The optimized LAMP was used to examine 18 field specimens collected from dead and clinically diseased geese and ducks aged from 1 to 12 weeks. The positive signal for GHPV was detected in three out of 18 (16.6%) specimens. These results were reproducible and consistent with those of four real-time PCR. To the best of our knowledge this is the first report on LAMP application for the GHPV detection.

  12. Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): Reproducibility of Polyomavirus Immunohistochemistry in Kidney Allografts

    PubMed Central

    Adam, Benjamin; Randhawa, Parmjeet; Chan, Samantha; Zeng, Gang; Regele, Heinz; Kushner, Yael B.; Colvin, Robert B.; Reeve, Jeff; Mengel, Michael

    2014-01-01

    Immunohistochemistry is the gold standard for diagnosing (positive versus negative) polyomavirus BK (BKV) nephropathy and has the potential for disease staging based on staining intensity and quantification of infected cells. This multicenter trial evaluated the reproducibility of BKV immunohistochemistry among 81 pathologists at 60 institutions. Participants stained tissue microarray slides and scored them for staining intensity and percentage of positive nuclei. Staining protocol details and evaluation scores were collected online. Slides were returned for centralized panel re-evaluation and kappa statistics were calculated. Individual assessment of staining intensity and percentage was more reproducible than combined scoring. Inter-institutional reproducibility was moderate for staining intensity (κ=0.49) and percentage (κ=0.42), fair for combined (κ=0.25), and best for simple positive/negative scoring (κ=0.63). Inter-observer reproducibility was substantial for intensity (κ=0.74), percentage (κ=0.66), and positive/negative (κ=0.67), and moderate for combined scoring (κ=0.43). Inter-laboratory reproducibility was fair for intensity (κ=0.37), percentage (κ=0.40), and combined (κ=0.24), but substantial for positive/negative scoring (κ=0.78). BKV RNA copies/cell correlated with staining intensity (r=0.56) and percentage (r=0.62). These results indicate that BKV immunohistochemistry is reproducible between observers but scoring should be simplified to a single-feature schema. Standardization of tissue processing and staining protocols would further improve inter-laboratory reproducibility. PMID:25091177

  13. Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

    PubMed

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-10-31

    MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

  14. JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection

    PubMed Central

    Wharton, Keith A.; Quigley, Catherine; Themeles, Marian; Dunstan, Robert W.; Doyle, Kathryn; Cahir-McFarland, Ellen; Wei, Jing; Buko, Alex; Reid, Carl E.; Sun, Chao; Carmillo, Paul; Sur, Gargi; Carulli, John P.; Mansfield, Keith G.; Westmoreland, Susan V.; Staugaitis, Susan M.; Fox, Robert J.; Meier, Werner; Goelz, Susan E.

    2016-01-01

    Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML. Sequence analysis of lesional brain tissue identified PML-associated viral mutations in regulatory (non-coding control region) DNA, capsid protein VP1, and the regulatory agnoprotein, as well as 9 novel mutations in capsid protein VP2, indicating rampant viral evolution. Nine samples, including three gross PML lesions and normal-appearing adjacent tissues, were characterized by histopathology and subject to quantitative genomic, proteomic, and molecular localization analyses. We observed a striking correlation between the spatial extent of demyelination, axonal destruction, and dispersion of JCV along white matter myelin sheath. Our observations in this case, as well as in a case of PML-like disease in an immunocompromised rhesus macaque, suggest that long-range spread of polyomavirus and axonal destruction in PML might involve extracellular association between virus and the white matter myelin sheath. PMID:27191595

  15. Applied antineutrino physics workshop.

    SciTech Connect

    Lund, James C.

    2008-01-01

    This workshop is the fourth one of a series that includes the Neutrino Geophysics Conference at Honolulu, Hawaii, which I attended in 2005. This workshop was organized by the Astro-Particle and Cosmology laboratory in the recently opened Condoret building of the University of Paris. More information, including copies of the presentations, on the workshop is available on the website: www.apc.univ-paris7.fr/AAP2007/. The workshop aims at opening neutrino physics to various fields such that it can be applied in geosciences, nuclear industry (reactor and spent fuel monitoring) and non-proliferation. The workshop was attended by over 60 people from Europe, USA, Asia and Brazil. The meeting was also attended by representatives of the Comprehensive nuclear-Test Ban Treaty (CTBT) and the International Atomic Energy Agency (IAEA). The workshop also included a workshop dinner on board of a river boat sailing the Seine river.

  16. BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP‐12

    PubMed Central

    Yakhontova, K.; Lu, M.; Manzetti, J.

    2015-01-01

    BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV‐specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)‐ and calcineurin‐inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR–SP6‐kinase activation. Sirolimus inhibition was rapid and effective up to 24 h postinfection during viral early gene expression, but not thereafter, during viral late gene expression. The mTORC‐1 kinase inhibitor torin‐1 showed a similar inhibition profile, supporting the notion that early steps of BKPyV replication depend on mTOR activity. Cyclosporine A also inhibited BKPyV replication, while tacrolimus activated BKPyV replication and reversed sirolimus inhibition. FK binding protein 12kda (FKBP‐12) siRNA knockdown abrogated sirolimus inhibition and increased BKPyV replication similar to adding tacrolimus. Thus, sirolimus and tacrolimus exert opposite effects on BKPyV replication in renal tubular epithelial cells by a mechanism involving FKBP‐12 as common target. Immunosuppressive drugs may therefore contribute directly to the risk of BKPyV replication and nephropathy besides suppressing T cell functions. The data provide rationales for clinical trials aiming at reducing the risk of BKPyV replication and disease in kidney transplantation. PMID:26639422

  17. Prevalence of Papillomaviruses, Polyomaviruses, and Herpesviruses in Triple-Negative and Inflammatory Breast Tumors from Algeria Compared with Other Types of Breast Cancer Tumors

    PubMed Central

    Corbex, Marilys; Bouzbid, Sabiha; Traverse-Glehen, Alexandra; Aouras, Hayette; McKay-Chopin, Sandrine; Carreira, Christine; Lankar, Abdelaziz; Tommasino, Massimo; Gheit, Tarik

    2014-01-01

    Background The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC) and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups. Materials and Methods One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria) to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses) using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology. Results Viral DNA was found in 22 (17.9%) of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type) than non-IBC tumors (30% vs. 13%, p<0.04). Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009). Conclusions Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative). While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings. PMID:25478862

  18. 75 FR 51829 - Public Workshop on Medical Devices and Nanotechnology: Manufacturing, Characterization, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... HUMAN SERVICES Food and Drug Administration Public Workshop on Medical Devices and Nanotechnology...) is announcing a public workshop entitled ``Medical Devices & Nanotechnology: Manufacturing... brief statement that describes your experience or expertise with nanotechnology. There will be a...

  19. 76 FR 55068 - Mobile Medical Applications Draft Guidance; Public Workshop; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... FR 50231). The document announced a public workshop entitled ``Mobile ] Medical Applications Draft... HUMAN SERVICES Food and Drug Administration Mobile Medical Applications Draft Guidance; Public Workshop... transcripts of the meeting?'' This document corrects that error. FOR FURTHER INFORMATION CONTACT: Joyce...

  20. 1981 NRC/BNL/IEEE standards workshop on human factors and nuclear safety. The man-machine interface and human reliability: an assessment and projection

    SciTech Connect

    Hall, R.E.; Fragola, J.R.; Luckas, W.J. Jr.

    1981-09-01

    The role of the human in the safety of nuclear power plant operations was addressed in a meeting held in Myrtle Beach, SC in August 1981. Presentation were made on Control Room reviews, safety parameter display systems, the integration of human factors in the entire design process, and the use of automated control features. A need was shown for the development of a taxonomy or model to structure future data gathering and the need for models and data to address the issue of cognitive behavior. The primary effect of this behavior on risk was identified. Discussion sessions on the human impact on reliability, and control room design and evaluation were included. (ACR)

  1. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults

    PubMed Central

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2015-01-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. PMID:26563978

  2. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

    PubMed

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2016-02-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

  3. Epidemiology of Environmental Exposures and Human Autoimmune Diseases: Findings from a National Institute of Environmental Health Sciences Expert Panel Workshop

    PubMed Central

    Alfredsson, Lars; Costenbader, Karen H.; Kamen, Diane L.; Nelson, Lorene; Norris, Jill M.; De Roos, Anneclaire J.

    2012-01-01

    Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future. PMID:22739348

  4. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.

    PubMed

    Miller, Frederick W; Alfredsson, Lars; Costenbader, Karen H; Kamen, Diane L; Nelson, Lorene M; Norris, Jill M; De Roos, Anneclaire J

    2012-12-01

    Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.

  5. Modeling and Simulation for Safeguards and Nonproliferation Workshop

    SciTech Connect

    Gilligan, Kimberly V.; Kirk, Bernadette Lugue

    2015-01-01

    The Modeling and Simulation for Safeguards and Nonproliferation Workshop was held December 15–18, 2014, at Oak Ridge National Laboratory. This workshop was made possible by the Next Generation Safeguards Initiative Human Capital Development (NGSI HCD) Program. The idea of the workshop was to move beyond the tried-and-true boot camp training of nonproliferation concepts to spend several days on the unique perspective of applying modeling and simulation (M&S) solutions to safeguards challenges.

  6. Solar education project workshop

    SciTech Connect

    Smith, J.B.

    1980-10-31

    A summary of proceedings of the Solar Education Project Workshop is presented. The workshop had as its focus the dissemination of curriculum materials developed by the Solar Energy Project of the New York State Department of Education under the sponsorship of the US Department of Energy. It includes, in addition to presentations by speakers and workshop leaders, specific comments from participants regarding materials available and energy-related activities underway in their respective states and suggested strategies from them for ongoing dissemination efforts.

  7. Lunar Commercialization Workshop

    NASA Technical Reports Server (NTRS)

    Martin, Gary L.

    2008-01-01

    This slide presentation describes the goals and rules of the workshop on Lunar Commercialization. The goal of the workshop is to explore the viability of using public-private partnerships to open the new space frontier. The bulk of the workshop was a team competition to create a innovative business plan for the commercialization of the moon. The public private partnership concept is reviewed, and the open architecture as an infrastructure for potential external cooperation. Some possible lunar commercialization elements are reviewed.

  8. Fermilab Cryogenic Workshop Report

    SciTech Connect

    Hassenzahl, W. V.

    1980-06-18

    A workshop to discuss recent pressing problems experienced in the operation of helium refrigerators at the national laboratories was proposed by DOE. Early in 1980 it was decided that the workshop should be held at the Fermi National Accelerator Laboratory (Fermilab). The reasoning behind the selection of Fermilab included the proposed initial tests of the Central Liquefier, the recently experienced problems with refrigeration systems at Fermilab, and the fact that a previous workshop had been held at the Brookhaven National Laboratory, which, at present, would be the other logical choice for the workshop.

  9. Alternate fusion fuels workshop

    SciTech Connect

    Not Available

    1981-06-01

    The workshop was organized to focus on a specific confinement scheme: the tokamak. The workshop was divided into two parts: systems and physics. The topics discussed in the systems session were narrowly focused on systems and engineering considerations in the tokamak geometry. The workshop participants reviewed the status of system studies, trade-offs between d-t and d-d based reactors and engineering problems associated with the design of a high-temperature, high-field reactor utilizing advanced fuels. In the physics session issues were discussed dealing with high-beta stability, synchrotron losses and transport in alternate fuel systems. The agenda for the workshop is attached.

  10. Thermal Barrier Coating Workshop

    NASA Technical Reports Server (NTRS)

    Brindley, W. J. (Compiler); Lee, W. Y. (Compiler); Goedjen, J. G. (Compiler); Dapkunas, S. J. (Compiler)

    1995-01-01

    This document contains the agenda and presentation abstracts for the Thermal Barrier Coating Workshop, sponsored by NASA, DOE, and NIST. The workshop covered thermal barrier coating (TBC) issues related to applications, processing, properties, and modeling. The intent of the workshop was to highlight the state of knowledge on TBC's and to identify critical gaps in knowledge that may hinder TBC use in advanced applications. The workshop goals were achieved through presentations by 22 speakers representing industry, academia, and government as well as through extensive discussion periods.

  11. CARE 3 User's Workshop

    NASA Technical Reports Server (NTRS)

    1988-01-01

    A user's workshop for CARE 3, a reliability assessment tool designed and developed especially for the evaluation of high reliability fault tolerant digital systems, was held at NASA Langley Research Center on October 6 to 7, 1987. The main purpose of the workshop was to assess the evolutionary status of CARE 3. The activities of the workshop are documented and papers are included by user's of CARE 3 and NASA. Features and limitations of CARE 3 and comparisons to other tools are presented. The conclusions to a workshop questionaire are also discussed.

  12. Sixth International Microgravity Combustion Workshop

    NASA Technical Reports Server (NTRS)

    Sacksteder, Kurt (Compiler)

    2001-01-01

    This conference proceedings document is a compilation of papers presented orally or as poster displays to the Sixth International Microgravity Combustion Workshop held in Cleveland, Ohio on May 22-24, 2001. The purpose of the workshop is to present and exchange research results from theoretical and experimental work in combustion science using the reduced-gravity environment as a research tool. The results are contributed by researchers funded by NASA throughout the United States at universities, industry and government research agencies, and by researchers from international partner countries that are also participating in the microgravity combustion science research discipline. These research results are intended for use by public and private sector organizations for academic purposes, for the development of technologies needed for Human Exploration and Development of Space, and to improve Earth-bound combustion and fire-safety related technologies.

  13. Nuclear thermal propulsion workshop overview

    NASA Technical Reports Server (NTRS)

    Clark, John S.

    1991-01-01

    NASA is planning an Exploration Technology Program as part of the Space Exploration Initiative to return U.S. astronauts to the moon, conduct intensive robotic exploration of the moon and Mars, and to conduct a piloted mission to Mars by 2019. Nuclear Propulsion is one of the key technology thrust for the human mission to Mars. The workshop addresses NTP (Nuclear Thermal Rocket) technologies with purpose to: assess the state-of-the-art of nuclear propulsion concepts; assess the potential benefits of the concepts for the mission to Mars; identify critical, enabling technologies; lay-out (first order) technology development plans including facility requirements; and estimate the cost of developing these technologies to flight-ready status. The output from the workshop will serve as a data base for nuclear propulsion project planning.

  14. Fifth International Microgravity Combustion Workshop

    NASA Technical Reports Server (NTRS)

    Sacksteder, Kurt (Compiler)

    1999-01-01

    This conference proceedings document is a compilation of 120 papers presented orally or as poster displays to the Fifth International Microgravity Combustion Workshop held in Cleveland, Ohio on May 18-20, 1999. The purpose of the workshop is to present and exchange research results from theoretical and experimental work in combustion science using the reduced-gravity environment as a research tool. The results are contributed by researchers funded by NASA throughout the United States at universities, industry and government research agencies, and by researchers from at least eight international partner countries that are also participating in the microgravity combustion science research discipline. These research results are intended for use by public and private sector organizations for academic purposes, for the development of technologies needed for the Human Exploration and Development of Space, and to improve Earth-bound combustion and fire-safety related technologies.

  15. Characterization of the non-coding control region of polyomavirus KI isolated from nasopharyngeal samples from patients with respiratory symptoms or infection and from blood from healthy blood donors in Norway.

    PubMed

    Song, Xiaobo; Van Ghelue, Marijke; Ludvigsen, Maria; Nordbø, Svein Arne; Ehlers, Bernhard; Moens, Ugo

    2016-07-01

    Seroepidemiological studies showed that the human polyomavirus KI (KIPyV) is common in the human population, with age-specific seroprevalence ranging from 40-90 %. Genome epidemiological analyses demonstrated that KIPyV DNA is predominantly found in respiratory tract samples of immunocompromised individuals and children suffering from respiratory diseases, but viral sequences have also been detected in brain, tonsil, lymphoid tissue studies, plasma, blood and faeces. Little is known about the sequence variation in the non-coding control region of KIPyV variants residing in different sites of the human body and whether specific strains dominate in certain parts of the world. In this study, we sequenced the non-coding control region (NCCR) of naturally occurring KIPyV variants in nasopharyngeal samples from patients with respiratory symptoms or infection and in blood from healthy donors in Norway. In total 86 sequences were obtained, 44 of which were identical to the original isolated Stockholm 60 variant. The remaining NCCRs contained one or several mutations, none of them previously reported. The same mutations were detected in NCCRs amplified from blood and nasopharyngeal samples. Some patients had different variants in their specimens. Transient transfection studies in HEK293 cells with a luciferase reporter plasmid demonstrated that some single mutations had a significant effect on the relative early and late promoter strength compared with the Stockholm 60 promoter. The effect of the NCCR mutations on viral replication and possible virulence properties remains to be established. PMID:27031170

  16. Efficacy of recombinant human interleukin 7 in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy.

    PubMed

    Gasnault, Jacques; de Goër de Herve, Marie-Ghislaine; Michot, Jean-Marie; Hendel-Chavez, Houria; Seta, Vannina; Mazet, Anne-Aurélie; Croughs, Thérèse; Stankoff, Bruno; Bourhis, Jean-Henri; Lambotte, Olivier; Delfraissy, Jean-François; Taoufik, Yassine

    2014-09-01

    In this study, we report the case of a patient with profound lymphopenia after allogenic bone marrow transplantation who developed severe progressive multifocal leukoencephalopathy. Single-agent recombinant human interleukin-7 therapy was associated with restoration of anti-John Cunningham polyomavirus (JCV) T-cell responses, JCV clearance from cerebrospinal fluid, and a dramatic clinical improvement. PMID:25734144

  17. Astrobiology Workshop: Leadership in Astrobiology

    NASA Technical Reports Server (NTRS)

    DeVincenzi, D. (Editor); Briggs, G.; Cohen, M.; Cuzzi, J.; DesMarais, D.; Harper, L.; Morrison, D.; Pohorille, A.

    1996-01-01

    Astrobiology is defined in the 1996 NASA Strategic Plan as 'The study of the living universe.' At NASA's Ames Research Center, this endeavor encompasses the use of space to understand life's origin, evolution, and destiny in the universe. Life's origin refers to understanding the origin of life in the context of the origin and diversity of planetary systems. Life's evolution refers to understanding how living systems have adapted to Earth's changing environment, to the all-pervasive force of gravity, and how they may adapt to environments beyond Earth. Life's destiny refers to making long-term human presence in space a reality, and laying the foundation for understanding and managing changes in Earth's environment. The first Astrobiology Workshop brought together a diverse group of researchers to discuss the following general questions: Where and how are other habitable worlds formed? How does life originate? How have the Earth and its biosphere influenced each other over time? Can terrestrial life be sustained beyond our planet? How can we expand the human presence to Mars? The objectives of the Workshop included: discussing the scope of astrobiology, strengthening existing efforts for the study of life in the universe, identifying new cross-disciplinary programs with the greatest potential for scientific return, and suggesting steps needed to bring this program to reality. Ames has been assigned the lead role for astrobiology by NASA in recognition of its strong history of leadership in multidisciplinary research in the space, Earth, and life sciences and its pioneering work in studies of the living universe. This initial science workshop was established to lay the foundation for what is to become a national effort in astrobiology, with anticipated participation by the university community, other NASA centers, and other agencies. This workshop (the first meeting of its kind ever held) involved life, Earth, and space scientists in a truly interdisciplinary sharing

  18. Immunity to Polyomavirus BK Infection: Immune Monitoring to Regulate the Balance between Risk of BKV Nephropathy and Induction of Alloimmunity

    PubMed Central

    Cioni, Michela; Basso, Sabrina; Gagliardone, Chiara; Potenza, Leonardo; Verrina, Enrico; Luppi, Mario; Zecca, Marco; Ghiggeri, Gian Marco; Ginevri, Fabrizio

    2013-01-01

    Polyomavirus BK-associated nephropathy (PyVAN) is the main infectious cause of allograft damage after kidney transplantation. A number of studies revealed an association between the presence of BKV-specific cellular immunity and BK viral clearance, with patients failing to recover specific T cells progressing to PyVAN. Evolution to allograft dysfunction can be prevented by restoration of BKV-specific immunity through a stepwise reduction of maintenance immunosuppressive drugs. Prospective monitoring of BK viral load and specific immunity, together with B-cell alloimmune surveillance, may allow a targeted modification/reduction of immunosuppression, with the aim of obtaining viral clearance while preventing graft injury due to deposition of de novo donor-specific HLA antibodies and late/chronic antibody-mediated allograft injury. Innovative, immune-based therapies may further contribute to BKV infection prevention and control. PMID:24000288

  19. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis

    PubMed Central

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-01-01

    AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS. PMID:26722657

  20. 78 FR 67168 - Sixth Annual Sentinel Initiative; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Sixth Annual Sentinel Initiative; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug...

  1. 76 FR 62419 - Science of Abuse Liability Assessment; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    .... SUPPLEMENTARY INFORMATION: In the Federal Register of January 27, 2010 (75 FR 4400), FDA announced the... HUMAN SERVICES Food and Drug Administration Science of Abuse Liability Assessment; Public Workshop... Food and Drug Administration (FDA) is announcing a public workshop to discuss the science of...

  2. Poetry Workshop. Holiday Snapshots.

    ERIC Educational Resources Information Center

    Cullinan, Bee

    1999-01-01

    This article describes a poetry workshop to create a snapshot of unique moments in family history during the holidays. The workshop includes a working on a family photo poetry poster and participating in extension activities (e.g., writing personal poetry notebooks). A reproducible offers a holiday album of poetry snapshots. (SM)

  3. Sensors Workshop summary report

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A review of the efforts of three workshops is presented. The presentation describes those technological developments that would contribute most to sensor subsystem optimization and improvement of NASA's data acquisition capabilities, and summarizes the recommendations of the sensor technology panels from the most recent workshops.

  4. Warehouse Sanitation Workshop Handbook.

    ERIC Educational Resources Information Center

    Food and Drug Administration (DHHS/PHS), Washington, DC.

    This workshop handbook contains information and reference materials on proper food warehouse sanitation. The materials have been used at Food and Drug Administration (FDA) food warehouse sanitation workshops, and are selected by the FDA for use by food warehouse operators and for training warehouse sanitation employees. The handbook is divided…

  5. Diaper industry workshop report

    SciTech Connect

    Not Available

    1991-05-01

    The report is the product of a one-day workshop on the diaper industry that was sponsored by the U.S. EPA. Four topics covered during the workshop were public health and safety, recycling, composting, and product life cycle analysis. The primary objective of the workshop was to identify areas within the diaper industry that need further research in order to lessen the adverse impacts that diapers have on the environment. Summaries of each of the four topics as well as summaries of discussion comments and research needs identified during the workshop are included in the report. A large number of research ideas were generated during the workshop. These ideas included determining the health risks associated with handling diapers, developing methods for improving the recyclability of plastics used in diapers, determining where diaper-related life cycle analysis should begin and end, and determining the economic viability of composting.

  6. 75 FR 51467 - ASK (Assess Specific Kinds of CHILDREN Challenges for Neurologic Devices) Study Children Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... HUMAN SERVICES Food and Drug Administration ASK (Assess Specific Kinds of CHILDREN Challenges for Neurologic Devices) Study Children Workshop; Public Workshop; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop; request for comments. SUMMARY: The Food and...

  7. Merkel Cell Carcinoma: A Virus-Induced Human Cancer

    PubMed Central

    Chang, Yuan; Moore, Patrick S.

    2013-01-01

    Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC. PMID:21942528

  8. New findings about trichodysplasia spinulosa-associated polyomavirus (TSPyV)--novel qPCR detects TSPyV-DNA in blood samples.

    PubMed

    Urbano, Paulo R; Nali, Luiz H S; Bicalho, Camila S; Pierrotti, Ligia C; David-Neto, Elias; Pannuti, Cláudio S; Romano, Camila M

    2016-02-01

    A new real-time PCR assay for trichodysplasia spinulosa-associated polyomavirus (TSPyV) DNA detection was designed, and blood samples from kidney transplant recipients and healthy individuals were screened. TSPyV-DNA was not detected in blood from healthy individuals, but 26.8% of kidney recipients presented TSPyV-DNA. This is the first report of TSPyV viremia.

  9. Conference report: interdisciplinary workshop in the philosophy of medicine: parentalism and trust.

    PubMed

    Bullock, Emma; Gergel, Tania; Kingma, Elselijn

    2015-06-01

    On 13 June 2014, the Centre for the Humanities and Health at King's College London hosted a 1-day workshop on 'parentalism and trust'. This workshop was the sixth in a series of workshops whose aim is to provide a new model for high-quality open interdisciplinary engagement between medical professionals and philosophers. This report briefly describes the workshop methodology and the discussions on the day.

  10. Computer Aided Drafting Workshop. Workshop Booklet.

    ERIC Educational Resources Information Center

    Goetsch, David L.

    This mini-course and article are presentations from a workshop on computer-aided drafting. The purpose of the mini-course is to assist drafting instructors in updating their occupational knowledge to include computer-aided drafting (CAD). Topics covered in the course include general computer information, the computer in drafting, CAD terminology,…

  11. Workshop by Design: Planning a Workshop.

    ERIC Educational Resources Information Center

    Spencer, Dorothy; Parsons, A. Chapman

    In an Ohio Library Association guide for planning workshops, detailed instructions are given for forming a committee, holding meetings, selecting and paying the speaker, and developing the program. Budgets and fees are discussed along with information on federal funding. Practical guidance is also provided about equipment, table arrangements,…

  12. On-site and off-site atmospheric PBDEs in an electronic dismantling workshop in south China: gas-particle partitioning and human exposure assessment.

    PubMed

    An, Taicheng; Zhang, Delin; Li, Guiying; Mai, Bixian; Fu, Jiamo

    2011-12-01

    Gas samples and total suspended particle during work and off work time were investigated on-site and off-site electronic waste dismantling workshop (I- and O-EWDW), then compared with plastic recycling workshop (PRW) and waste incineration plant (WIP). TSP concentrations and total PBDE were 0.36-2.21 mg/m(3) and 27-2975 ng/m(3) at different workshops, respectively. BDE-47, -99, and -209 were major ∑PBDE congeners at I-EWDW and WIP, while BDE-209 was only dominant congener in PRW and control sites during work time and all sites during off work time. The gas-particle partitioning result was well correlated with the subcooled liquid vapor pressure for all samples, except for WIP and I-EDWD, at park during work time, and residential area during off work time. The predicted urban curve fitted well with measured φ values at O-DEWD during work time, whereas it was slightly overestimated or underestimated for others. Exposure assessment revealed the highest exposure site was I-EDWD.

  13. Nuclear Innovation Workshops Report

    SciTech Connect

    Jackson, John Howard; Allen, Todd Randall; Hildebrandt, Philip Clay; Baker, Suzanne Hobbs

    2015-09-01

    The Nuclear Innovation Workshops were held at six locations across the United States on March 3-5, 2015. The data collected during these workshops has been analyzed and sorted to bring out consistent themes toward enhancing innovation in nuclear energy. These themes include development of a test bed and demonstration platform, improved regulatory processes, improved communications, and increased public-private partnerships. This report contains a discussion of the workshops and resulting themes. Actionable steps are suggested at the end of the report. This revision has a small amount of the data in Appendix C removed in order to avoid potential confusion.

  14. Ocean margins workshop

    SciTech Connect

    1990-12-31

    The Department of Energy (DOE) is announcing the refocusing of its marine research program to emphasize the study of ocean margins and their role in modulating, controlling, and driving Global Change phenomena. This is a proposal to conduct a workshop that will establish priorities and an implementation plan for a new research initiative by the Department of Energy on the ocean margins. The workshop will be attended by about 70 scientists who specialize in ocean margin research. The workshop will be held in the Norfolk, Virginia area in late June 1990.

  15. Soil Moisture Workshop

    NASA Technical Reports Server (NTRS)

    Heilman, J. L. (Editor); Moore, D. G. (Editor); Schmugge, T. J. (Editor); Friedman, D. B. (Editor)

    1978-01-01

    The Soil Moisture Workshop was held at the United States Department of Agriculture National Agricultural Library in Beltsville, Maryland on January 17-19, 1978. The objectives of the Workshop were to evaluate the state of the art of remote sensing of soil moisture; examine the needs of potential users; and make recommendations concerning the future of soil moisture research and development. To accomplish these objectives, small working groups were organized in advance of the Workshop to prepare position papers. These papers served as the basis for this report.

  16. Biomedical Polar Research Workshop Minutes

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This workshop was conducted to provide a background of NASA and National Science Foundation goals, an overview of previous and current biomedical research, and a discussion about areas of potential future joint activities. The objectives of the joint research were: (1) to develop an understanding of the physiological, psychological, and behavioral alterations and adaptations to extreme environments of the polar regions; (2) to ensure the health, well-being, and performance of humans in these environments; and (3) to promote the application of biomedical research to improve the quality of life in all environments.

  17. 76 FR 64353 - Buy Quiet Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... HUMAN SERVICES Centers for Disease Control and Prevention Buy Quiet Workshop AGENCY: National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC... Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention...

  18. From Workshop to Classroom: Bridging GIS Success

    ERIC Educational Resources Information Center

    Stonier, Francis; Hong, Jung Eun

    2016-01-01

    This article shares the first-time geographic information system (GIS) experiences of two advanced placement human geography classes. The teacher had participated in a summer GIS workshop and then brought those skills into her classroom for the students' benefit. Eighteen students shared their experiences researching their family history, working…

  19. Workshop overview: Arsenic research and risk assessment

    SciTech Connect

    Sams, Reeder Wolf, Douglas C.; Ramasamy, Santhini; Ohanian, Ed; Chen, Jonathan; Lowit, Anna

    2007-08-01

    The chronic exposure of humans through consumption of high levels of inorganic arsenic (iAs)-contaminated drinking water is associated with skin lesions, peripheral vascular disease, hypertension, and cancers. Additionally, humans are exposed to organic arsenicals when used as pesticides and herbicides (e.g., monomethylarsonic acid, dimethylarsinic acid (DMA{sup V}) also known as cacodylic acid). Extensive research has been conducted to characterize the adverse health effects that result from exposure to iAs and its metabolites to describe the biological pathway(s) that lead to adverse health effects. To further this effort, on May 31, 2006, the United States Environmental Protection Agency (USEPA) sponsored a meeting entitled 'Workshop on Arsenic Research and Risk Assessment'. The invited participants from government agencies, academia, independent research organizations and consultants were asked to present their current research. The overall focus of these research efforts has been to determine the potential human health risks due to environmental exposures to arsenicals. Pursuant in these efforts is the elucidation of a mode of action for arsenicals. This paper provides a brief overview of the workshop goals, regulatory context for arsenical research, mode of action (MOA) analysis in human health risk assessment, and the application of MOA analysis for iAs and DMA{sup V}. Subsequent papers within this issue will present the research discussed at the workshop, ensuing discussions, and conclusions of the workshop.

  20. TCGA Workshop: Genomics and Biology of Glioblastoma Multiforme (GBM) - TCGA

    Cancer.gov

    The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) held a workshop entitled, “Genomics and Biology of Glioblastoma Multiforme (GBM),” to review the initial GBM data from the TCGA pilot project.

  1. The Career Development Workshop

    ERIC Educational Resources Information Center

    Marsh, P. J.

    1973-01-01

    This article describes a career planning workshop for managers and its purpose is to support and accelerate the process of individual development without organizational coercion or manipulation. (Author/RK)

  2. Transportation Management Workshop: Proceedings

    SciTech Connect

    Not Available

    1993-10-01

    This report is a compilation of discussions presented at the Transportation Management Workshop held in Gaithersburg, Maryland. Topics include waste packaging, personnel training, robotics, transportation routing, certification, containers, and waste classification.

  3. An Aerospace Workshop

    ERIC Educational Resources Information Center

    Hill, Bill

    1972-01-01

    Describes the 16-day, 10,000 mile national tour of the nation's major aerospace research and development centers by 65 students enrolled in Central Washington State College's Summer Aerospace Workshop. (Author/MB)

  4. Special parallel processing workshop

    SciTech Connect

    1994-12-01

    This report contains viewgraphs from the Special Parallel Processing Workshop. These viewgraphs deal with topics such as parallel processing performance, message passing, queue structure, and other basic concept detailing with parallel processing.

  5. Complex Flow Workshop Report

    SciTech Connect

    none,

    2012-05-01

    This report documents findings from a workshop on the impacts of complex wind flows in and out of wind turbine environments, the research needs, and the challenges of meteorological and engineering modeling at regional, wind plant, and wind turbine scales.

  6. Highly Autonomous Systems Workshop

    NASA Technical Reports Server (NTRS)

    Doyle, R.; Rasmussen, R.; Man, G.; Patel, K.

    1998-01-01

    It is our aim by launching a series of workshops on the topic of highly autonomous systems to reach out to the larger community interested in technology development for remotely deployed systems, particularly those for exploration.

  7. Successful Workshop Planning.

    ERIC Educational Resources Information Center

    Gates, Barbara A.

    1980-01-01

    Offers suggestions concerning important elements in planning workshops: organization of committees, program planning, definition of topic and purpose, statement of objectives, the audience, format, timing, site selection, registration, publicity, speaker selection, contracts, budgets, and evaluation questionnaires. (FM)

  8. Cybernetics and Workshop Design.

    ERIC Educational Resources Information Center

    Eckstein, Daniel G.

    1979-01-01

    Cybernetic sessions allow for the investigation of several variables concurrently, resulting in a large volume of input compacted into a concise time frame. Three session questions are reproduced to illustrate the variety of ideas generated relative to workshop design. (Author)

  9. ISIS Workshops Using Virtualization

    NASA Astrophysics Data System (ADS)

    Becker, K. J.; Becker, T. L.

    2015-06-01

    ISIS workshops are now using virtualization technology to improve the user experience and create a stable, consistent and useful ISIS installation for educational purposes as well as future processing needs.

  10. Workshop: Teaching Primitive Arts.

    ERIC Educational Resources Information Center

    Jordison, Jerry

    1999-01-01

    Discusses the concrete and spiritual aspects of teaching workshops on survival skills or primitive arts. Gives details on lostproofing, or ways to teach a child not to get lost in the outdoors; building a survival shelter; and wilderness cooking. (CDS)

  11. Kepler Mission IYA Teacher Professional Development Workshops

    NASA Astrophysics Data System (ADS)

    Devore, E. K.; Harman, P.; Gould, A. D.; Koch, D.

    2009-12-01

    NASA's Kepler Mission conducted six teacher professional development workshops on the search for Earth-size in the habitable zone of Sun-like stars. The Kepler Mission launched in March, 2009. As a part of International Year of Astronomy 2009, this series of one-day workshops were designed and presented for middle and high school teachers, and science center and planetarium educators prior to and after the launch. The professional development workshops were designed using the best practices and principals from the National Science Education Standards and similar documents. Sharing the outcome of our plans, strategies and formative evaluation results can be of use to other Education and Public Outreach practitioners who plan similar trainings. Each event was supported by a Kepler team scientist, two Education & Public Outreach staff and local hosts. The workshops combined a science content lecture and discussion, making models, kinesthetic activities, and interpretation of transit data. The emphasis was on inquiry-based instruction and supported science education standards in grades 7-12. Participants’ kit included an orrery, optical sensor and software to demonstrate transit detection. The workshop plan, teaching strategies, and lessons learned from evaluation will be discussed. Future events are planned. Kepler's Education and Public Outreach program is jointly conducted by the SETI Institute and Lawrence Hall of Science at UC Berkeley in close coordination with the Kepler Mission at NASA Ames Research Center. The IYA Kepler Teacher Professional Development workshops were supported by NASA Grants to the E. DeVore, SETI Institute NAG2-6066 Kepler Education and Public Outreach and NNX08BA74G, IYA Kepler Mission Pre-launch Workshops. Teachers participate in human orrery.

  12. Workshop I: Gender Studies

    NASA Astrophysics Data System (ADS)

    Hennessey, Eden; Kurup, Anitha; Meza-Montes, Lilia; Shastri, Prajval; Ghose, Shohini

    2015-12-01

    Participants in the Gender Studies workshop of the 5th IUPAP International Conference on Women in Physics discussed the gender question in science practice from a policy perspective, informed by investigations from the social science disciplines. The workshop's three sessions—"Equity and Education: Examining Gender Stigma in Science," "A Comparative Study of Women Scientists and Engineers: Experiences in India and the US," and "Toward Gender Equity Through Policy: Characterizing the Social Impact of Interventions—are summarized, and the resulting recommendations presented.

  13. OEXP Analysis Tools Workshop

    NASA Technical Reports Server (NTRS)

    Garrett, L. Bernard; Wright, Robert L.; Badi, Deborah; Findlay, John T.

    1988-01-01

    This publication summarizes the software needs and available analysis tools presented at the OEXP Analysis Tools Workshop held at the NASA Langley Research Center, Hampton, Virginia on June 21 to 22, 1988. The objective of the workshop was to identify available spacecraft system (and subsystem) analysis and engineering design tools, and mission planning and analysis software that could be used for various NASA Office of Exploration (code Z) studies, specifically lunar and Mars missions.

  14. Industrial Fuel Flexibility Workshop

    SciTech Connect

    none,

    2006-09-01

    On September 28, 2006, in Washington, DC, ITP and Booz Allen Hamilton conducted a fuel flexibility workshop with attendance from various stakeholder groups. Workshop participants included representatives from the petrochemical, refining, food and beverage, steel and metals, pulp and paper, cement and glass manufacturing industries; as well as representatives from industrial boiler manufacturers, technology providers, energy and waste service providers, the federal government and national laboratories, and developers and financiers.

  15. Space Mechanisms Technology Workshop

    NASA Technical Reports Server (NTRS)

    Oswald, Fred B. (Editor)

    2002-01-01

    The Mechanical Components Branch at NASA Glenn Research Center hosted a workshop on Tuesday, May 14, 2002, to discuss space mechanisms technology. The theme for this workshop was 'Working in the Cold,' a focus on space mechanisms that must operate at low temperatures. We define 'cold' as below -60C (210 K), such as would be found near the equator of Mars. However, we are also concerned with much colder temperatures such as in permanently dark craters of the Moon (about 40 K).

  16. Space Mechanisms Technology Workshop

    NASA Technical Reports Server (NTRS)

    Oswald, Fred B. (Editor)

    2001-01-01

    The Mechanical Components Branch at NASA Glenn Research Center hosted a workshop to discuss the state of drive systems technology needed for space exploration. The Workshop was held Thursday, November 2, 2000. About 70 space mechanisms experts shared their experiences from working in this field and considered technology development that will be needed to support future space exploration in the next 10 to 30 years.

  17. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    PubMed

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

  18. An International Workshop on Primary Science. Report on the Primary Science Workshop Held after the Conference in Science and Technology Education and Future Human Needs (Bangalore, India, August 1985).

    ERIC Educational Resources Information Center

    Harlen, Wynne, Comp.

    A conference on science and technology and future human needs was attended by over 300 science educators from 64 countries. Educators with particular interest in primary science and technology education extended their stay for an additional seminar. This report highlights the events of that seminar. Contents include: (1) recent and on-going work…

  19. International Lighting in Controlled Environments Workshop

    NASA Technical Reports Server (NTRS)

    Tibbits, Ted W. (Editor)

    1994-01-01

    Lighting is a central and critical aspect of control in environmental research for plant research and is gaining recognition as a significant factor to control carefully for animal and human research. Thus this workshop was convened to reevaluate the technology that is available today and to work toward developing guidelines for the most effective use of lighting in controlled environments with emphasis on lighting for plants but also to initiate interest in the development of improved guidelines for human and animal research.

  20. Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing

    PubMed Central

    Garren, Seth B.; Kondaveeti, Yuvabharath; Duff, Michael O.; Carmichael, Gordon G.

    2015-01-01

    Mouse polyomavirus (MPyV) lytically infects mouse cells, transforms rat cells in culture, and is highly oncogenic in rodents. We have used deep sequencing to follow MPyV infection of mouse NIH3T6 cells at various times after infection and analyzed both the viral and cellular transcriptomes. Alignment of sequencing reads to the viral genome illustrated the transcriptional profile of the early-to-late switch with both early-strand and late-strand RNAs being transcribed at all time points. A number of novel insights into viral gene expression emerged from these studies, including the demonstration of widespread RNA editing of viral transcripts at late times in infection. By late times in infection, 359 host genes were seen to be significantly upregulated and 857 were downregulated. Gene ontology analysis indicated transcripts involved in translation, metabolism, RNA processing, DNA methylation, and protein turnover were upregulated while transcripts involved in extracellular adhesion, cytoskeleton, zinc finger binding, SH3 domain, and GTPase activation were downregulated. The levels of a number of long noncoding RNAs were also altered. The long noncoding RNA MALAT1, which is involved in splicing speckles and used as a marker in many late-stage cancers, was noticeably downregulated, while several other abundant noncoding RNAs were strongly upregulated. We discuss these results in light of what is currently known about the MPyV life cycle and its effects on host cell growth and metabolism. PMID:26407100

  1. Aphidicolin-resistant polyomavirus and subgenomic cellular DNA synthesis occur early in the differentiation of cultured myoblasts to myotubes.

    PubMed Central

    DePolo, N J; Villarreal, L P

    1993-01-01

    Small DNA viruses have been historically used as probes of cellular control mechanisms of DNA replication, gene expression, and differentiation. Polyomavirus (Py) DNA replication is known to be linked to differentiation of may cells, including myoblasts. In this report, we use this linkage in myoblasts to simultaneously examine (i) cellular differentiation control of Py DNA replication and (ii) an unusual type of cellular and Py DNA synthesis during differentiation. Early proposals that DNA synthesis was involved in the induced differentiation of myoblasts to myotubes were apparently disproved by reliance on inhibitors of DNA synthesis (cytosine arabinoside and aphidicolin), which indicated that mitosis and DNA replication are not necessary for differentiation. Theoretical problems with the accessibility of inactive chromatin to trans-acting factors led us to reexamine possible involvement of DNA replication in myoblast differentiation. We show here that Py undergoes novel aphidicolin-resistant net DNA synthesis under specific conditions early in induced differentiation of myoblasts (following delayed aphidicolin addition). Under similar conditions, we also examined uninfected myoblast DNA synthesis, and we show that soon after differentiation induction, a period of aphidicolin-resistant cellular DNA synthesis can also be observed. This drug-resistant DNA synthesis appears to be subgenomic, not contributing to mitosis, and more representative of polyadenylated than of nonpolyadenylated RNA. These results renew the possibility that DNA synthesis plays a role in myoblast differentiation and suggest that the linkage of Py DNA synthesis to differentiation may involve a qualitative cellular alteration in Py DNA replication. Images PMID:8389922

  2. Prevalence and genetic characterization of avian polyomavirus and psittacine beak and feather disease virus isolated from budgerigars in Mainland China.

    PubMed

    Zhuang, Qingye; Chen, Jiming; Mushtaq, Muhammad Hassan; Chen, Jie; Liu, Shuo; Hou, Guangyu; Li, Jinping; Huang, Baoxu; Jiang, Wenming

    2012-01-01

    Budgerigar fledgling disease (BFD) and psittacine beak and feather disease (PBFD) are caused by avian polyomavirus (APV) and psittacine beak and feather disease virus (PBFDV), respectively. These diseases frequently infect psittacine birds and result in similar clinical manifestations. In this study, we observed the prevalence of PBFDV infection and a dual infection of APV and PBFDV in a budgerigar (Melopsittacus undulatus) in Mainland China for the first time. One PBFDV isolate and two APV isolates were harvested using chicken embryos. Genetic characterization and phylogenetic analysis of the complete genome of the two APV isolates revealed nucleotide similarity ranging from 99.0% to 99.6% to other sequences in GenBank, and a 14-bp insertion was observed in the genome of one APV isolate. The results of complete genome analysis of the PBFDV isolate showed nucleotide similarity ranging from 83.0% to 95.0% with other PBFDV sequences in GenBank. Genetic characterization and phylogenetic analysis of the APV and PBFDV strains isolated in this study indicated that the isolates from China were closely related to their Japanese counterparts. The results of this study will help to identify molecular determinants and will aid further research on the prevention and control of APV and PBFD infection. PMID:22002652

  3. Antibodies to Merkel cell polyomavirus T-antigen oncoproteins reflect tumor burden in Merkel cell carcinoma patients

    PubMed Central

    Paulson, Kelly G.; Carter, Joseph J.; Johnson, Lisa G.; Cahill, Kevin W.; Iyer, Jayasri G.; Schrama, David; Becker, Juergen C.; Madeleine, Margaret M.; Nghiem, Paul; Galloway, Denise A.

    2010-01-01

    Merkel cell polyomavirus (MCPyV) is a common infectious agent that is likely involved in the etiology of most Merkel cell carcinomas (MCCs). Serum antibodies recognizing the MCPyV capsid protein, VP1, are detectable at high titer in nearly all MCC patients, and remain stable over time. Although antibodies to the viral capsid indicate prior MCPyV infection, they provide limited clinical insight into MCC because they are also detected in more than half of the general population. We investigated whether antibodies recognizing MCPyV large and small tumor-associated antigens (T-Ags) would be more specifically associated with MCC. Among 530 population control subjects, these antibodies were present in only 0.9% and were of low titer. In contrast, among 205 MCC cases, 40.5% had serum IgG antibodies that recognize a portion of T-Ag shared between small and large T-Ags. Among cases, titers of T-Ag antibodies fell rapidly (approximately 8 fold/year) in patients whose cancer did not recur, while they rose rapidly in those with progressive disease. Importantly, in several patients who developed metastases, the rise in T-Ag titer preceded clinical detection of disease spread. These results suggest that antibodies recognizing T-Ag are relatively specifically associated with MCC, do not effectively protect against disease progression, and may serve as a clinically useful indicator of disease status. PMID:20959478

  4. Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

    SciTech Connect

    Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer; Hirsch, Hans H.; Rinaldo, Christine Hanssen

    2010-03-01

    High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.

  5. Tubulointerstitial Nephritis Due to a Mutant Polyomavirus BK Virus Strain, BKV(Cin), Causing End-Stage Renal Disease

    PubMed Central

    Smith, R. D.; Galla, J. H.; Skahan, K.; Anderson, P.; Linnemann, C. C.; Ault, G. S.; Ryschkewitsch, C. F.; Stoner, G. L.

    1998-01-01

    A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG→AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity. PMID:9620396

  6. t4 Workshop Report*

    PubMed Central

    Kleensang, Andre; Maertens, Alexandra; Rosenberg, Michael; Fitzpatrick, Suzanne; Lamb, Justin; Auerbach, Scott; Brennan, Richard; Crofton, Kevin M.; Gordon, Ben; Fornace, Albert J.; Gaido, Kevin; Gerhold, David; Haw, Robin; Henney, Adriano; Ma’ayan, Avi; McBride, Mary; Monti, Stefano; Ochs, Michael F.; Pandey, Akhilesh; Sharan, Roded; Stierum, Rob; Tugendreich, Stuart; Willett, Catherine; Wittwehr, Clemens; Xia, Jianguo; Patton, Geoffrey W.; Arvidson, Kirk; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Adeleye, Yeyejide; Kanehisa, Minoru; Carmichael, Paul; Andersen, Melvin E.; Hartung, Thomas

    2014-01-01

    Summary Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation – the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as “A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants”. It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities. PMID:24127042

  7. The QED Workshop

    SciTech Connect

    Pieper, G.W.

    1994-07-01

    On May 18--20, 1994, Argonne National Laboratory hosted the QED Workshop. The workshop was supported by special funding from the Office of Naval Research. The purpose of the workshop was to assemble of a group of researchers to consider whether it is desirable and feasible to build a proof-checked encyclopedia of mathematics, with an associated facility for theorem proving and proof checking. Among the projects represented were Coq, Eves, HOL, ILF, Imps, MathPert, Mizar, NQTHM, NuPrl, OTTER, Proof Pad, Qu-Prolog, and RRL. Although the content of the QED project is highly technical rigorously proof-checked mathematics of all sorts the discussions at the workshop were rarely technical. No prepared talks or papers were given. Instead, the discussions focused primarily on such political, sociological, practical, and aesthetic questions, such as Why do it? Who are the customers? How can one get mathematicians interested? What sort of interfaces are desirable? The most important conclusion of the workshop was that QED is an idea worthy pursuing, a statement with which virtually all the participants agreed. In this document, the authors capture some of the discussions and outline suggestions for the start of a QED scientific community.

  8. 75 FR 74736 - Food Labeling Workshop; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... Time: This public workshop will be held on March 3 and 4, 2011, from 8 a.m. to 5 p.m. Location: The... employees. Seats are limited; please submit your registration as soon as possible. Workshop space will be... possible on a space available basis on the day of the public workshop beginning at 8 a.m. The cost...

  9. Cognition in Space Workshop. 1; Metrics and Models

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Fielder, Edna

    2005-01-01

    "Cognition in Space Workshop I: Metrics and Models" was the first in a series of workshops sponsored by NASA to develop an integrated research and development plan supporting human cognition in space exploration. The workshop was held in Chandler, Arizona, October 25-27, 2004. The participants represented academia, government agencies, and medical centers. This workshop addressed the following goal of the NASA Human System Integration Program for Exploration: to develop a program to manage risks due to human performance and human error, specifically ones tied to cognition. Risks range from catastrophic error to degradation of efficiency and failure to accomplish mission goals. Cognition itself includes memory, decision making, initiation of motor responses, sensation, and perception. Four subgoals were also defined at the workshop as follows: (1) NASA needs to develop a human-centered design process that incorporates standards for human cognition, human performance, and assessment of human interfaces; (2) NASA needs to identify and assess factors that increase risks associated with cognition; (3) NASA needs to predict risks associated with cognition; and (4) NASA needs to mitigate risk, both prior to actual missions and in real time. This report develops the material relating to these four subgoals.

  10. Report on the Consensus Workshop on Formaldehyde.

    PubMed Central

    1984-01-01

    The Consensus Workshop on Formaldehyde consisted of bringing together scientists from academia, government, industry and public interest groups to address some important toxicological questions concerning the health effects of formaldehyde. The participants in the workshop, the Executive Panel which coordinated the meeting, and the questions posed, all were chosen through a broadly based nomination process in order to achieve as comprehensive a consensus as possible. The subcommittees considered the toxicological problems associated with formaldehyde in the areas of exposure, epidemiology, carcinogenicity/histology/genotoxicity, immunology/sensitization/irritation, structure activity/biochemistry/metabolism, reproduction/teratology, behavior/neurotoxicity/psychology and risk estimation. Some questions considered included the possible human carcinogenicity of formaldehyde, as well as other human health effects, and the interpretation of pathology induced by formaldehyde. These reports, plus introductory material on the procedures used in setting up the Consensus Workshop are presented here. Additionally, there is included a listing of the data base that was made available to the panel chairmen prior to the meeting and was readily accessible to the participants during their deliberations in the meeting. This data base, since it was computerized, was also capable of being searched for important terms. These materials were supplemented by information brought by the panelists. The workshop has defined the consensus concerning a number of major points in formaldehyde toxicology and has identified a number of major deficits in understanding which are important guides to future research. PMID:6525992

  11. Space Station Workstation Technology Workshop Report

    NASA Technical Reports Server (NTRS)

    Moe, K. L.; Emerson, C. M.; Eike, D. R.; Malone, T. B.

    1985-01-01

    This report describes the results of a workshop conducted at Goddard Space Flight Center (GSFC) to identify current and anticipated trends in human-computer interface technology that may influence the design or operation of a space station workstation. The workshop was attended by approximately 40 persons from government and academia who were selected for their expertise in some aspect of human-machine interaction research. The focus of the workshop was a 1 1/2 brainstorming/forecasting session in which the attendees were assigned to interdisciplinary working groups and instructed to develop predictions for each of the following technology areas: (1) user interface, (2) resource management, (3) control language, (4) data base systems, (5) automatic software development, (6) communications, (7) training, and (8) simulation. This report is significant in that it provides a unique perspective on workstation design for the space station. This perspective, which is characterized by a major emphasis on user requirements, should be most valuable to Phase B contractors involved in design development of the space station workstation. One of the more compelling results of the workshop is the recognition that no major technological breakthroughs are required to implement the current workstation concept. What is required is the creative application of existing knowledge and technology.

  12. Space Station Workstation Technology Workshop Report

    NASA Astrophysics Data System (ADS)

    Moe, K. L.; Emerson, C. M.; Eike, D. R.; Malone, T. B.

    1985-03-01

    This report describes the results of a workshop conducted at Goddard Space Flight Center (GSFC) to identify current and anticipated trends in human-computer interface technology that may influence the design or operation of a space station workstation. The workshop was attended by approximately 40 persons from government and academia who were selected for their expertise in some aspect of human-machine interaction research. The focus of the workshop was a 1 1/2 brainstorming/forecasting session in which the attendees were assigned to interdisciplinary working groups and instructed to develop predictions for each of the following technology areas: (1) user interface, (2) resource management, (3) control language, (4) data base systems, (5) automatic software development, (6) communications, (7) training, and (8) simulation. This report is significant in that it provides a unique perspective on workstation design for the space station. This perspective, which is characterized by a major emphasis on user requirements, should be most valuable to Phase B contractors involved in design development of the space station workstation. One of the more compelling results of the workshop is the recognition that no major technological breakthroughs are required to implement the current workstation concept. What is required is the creative application of existing knowledge and technology.

  13. Measurement control workshop instructional materials

    SciTech Connect

    Gibbs, Philip; Crawford, Cary; McGinnis, Brent

    2014-04-01

    A workshop to teach the essential elements of an effective nuclear materials control and accountability (MC&A) programs are outlined, along with the modes of Instruction, and the roles and responsibilities of participants in the workshop.

  14. Thin film solar cell workshop

    NASA Technical Reports Server (NTRS)

    Armstrong, Joe; Jeffrey, Frank

    1993-01-01

    A summation of responses to questions posed to the thin-film solar cell workshop and the ensuing discussion is provided. Participants in the workshop included photovoltaic manufacturers (both thin film and crystalline), cell performance investigators, and consumers.

  15. Workshop on Molecular Animation

    PubMed Central

    Bromberg, Sarina; Chiu, Wah; Ferrin, Thomas E.

    2011-01-01

    Summary February 25–26, 2010, in San Francisco, the Resource for Biocomputing, Visualization and Informatics (RBVI) and the National Center for Macromolecular Imaging (NCMI) hosted a molecular animation workshop for 21 structural biologists, molecular animators, and creators of molecular visualization software. Molecular animation aims to visualize scientific understanding of biomolecular processes and structures. The primary goal of the workshop was to identify the necessary tools for: producing high quality molecular animations, understanding complex molecular and cellular structures, creating publication supplementary materials and conference presentations, and teaching science to students and the public. Another use of molecular animation emerged in the workshop: helping to focus scientific inquiry about the motions of molecules and enhancing informal communication within and between laboratories. PMID:20947014

  16. Workshop on molecular animation.

    PubMed

    Bromberg, Sarina; Chiu, Wah; Ferrin, Thomas E

    2010-10-13

    From February 25 to 26, 2010, in San Francisco, the Resource for Biocomputing, Visualization, and Informatics (RBVI) and the National Center for Macromolecular Imaging (NCMI) hosted a molecular animation workshop for 21 structural biologists, molecular animators, and creators of molecular visualization software. Molecular animation aims to visualize scientific understanding of biomolecular processes and structures. The primary goal of the workshop was to identify the necessary tools for producing high-quality molecular animations, understanding complex molecular and cellular structures, creating publication supplementary materials and conference presentations, and teaching science to students and the public. Another use of molecular animation emerged in the workshop: helping to focus scientific inquiry about the motions of molecules and enhancing informal communication within and between laboratories.

  17. Final Scientific EFNUDAT Workshop

    ScienceCinema

    None

    2016-07-12

    The Final Scientific EFNUDAT Workshop - organized by the CERN/EN-STI group on behalf of n_TOF Collaboration - will be held at CERN, Geneva (Switzerland) from 30 August to 2 September 2010 inclusive.EFNUDAT website: http://www.efnudat.euTopics of interest include: Data evaluationCross section measurementsExperimental techniquesUncertainties and covariancesFission propertiesCurrent and future facilities  International Advisory Committee: C. Barreau (CENBG, France)T. Belgya (IKI KFKI, Hungary)E. Gonzalez (CIEMAT, Spain)F. Gunsing (CEA, France)F.-J. Hambsch (IRMM, Belgium)A. Junghans (FZD, Germany)R. Nolte (PTB, Germany)S. Pomp (TSL UU, Sweden) Workshop Organizing Committee: Enrico Chiaveri (Chairman)Marco CalvianiSamuel AndriamonjeEric BerthoumieuxCarlos GuerreroRoberto LositoVasilis Vlachoudis Workshop Assistant: Géraldine Jean

  18. European Stroke Science Workshop

    PubMed Central

    Mattle, Heinrich P.; Brainin, Michael; Chamorro, Angel; Diener, Hans Christoph; Hacke, Werner; Leys, Didier; Norrving, Bo; Ward, Nick

    2012-01-01

    The European Stroke Organisation (ESO) held its first European Stroke Science Workshop in Garmisch-Partenkirchen, Germany (15-17 December 2011). Stroke experts based in Europe were invited to present and discuss their current research. The scope of the workshop was to review the most recent findings of selected topics in stroke, to exchange ideas, to stimulate new research and to enhance collaboration between European stroke research groups. Seven scientific sessions were held, each starting with a keynote lecture to review the state of the art of the given topic, followed by 4 or 5 short presentations by experts. They were asked to limit their presentations to 10 slides containing only recent information. The meeting was organized by the executive committee of the ESO (Heinrich Mattle, chairman, Michael Brainin, Angel Chamorro, Werner Hacke, Didier Leys) and supported by the European Stroke Conference (Michael Hennerici). In this article we summarize the main contents of this successful workshop. PMID:22836350

  19. Final Scientific EFNUDAT Workshop

    SciTech Connect

    2010-11-09

    The Final Scientific EFNUDAT Workshop - organized by the CERN/EN-STI group on behalf of n_TOF Collaboration - will be held at CERN, Geneva (Switzerland) from 30 August to 2 September 2010 inclusive.EFNUDAT website: http://www.efnudat.euTopics of interest include: Data evaluationCross section measurementsExperimental techniquesUncertainties and covariancesFission propertiesCurrent and future facilities  International Advisory Committee: C. Barreau (CENBG, France)T. Belgya (IKI KFKI, Hungary)E. Gonzalez (CIEMAT, Spain)F. Gunsing (CEA, France)F.-J. Hambsch (IRMM, Belgium)A. Junghans (FZD, Germany)R. Nolte (PTB, Germany)S. Pomp (TSL UU, Sweden) Workshop Organizing Committee: Enrico Chiaveri (Chairman)Marco CalvianiSamuel AndriamonjeEric BerthoumieuxCarlos GuerreroRoberto LositoVasilis Vlachoudis Workshop Assistant: Géraldine Jean

  20. The Astronomy Workshop

    NASA Astrophysics Data System (ADS)

    Hamilton, D. P.; Asbury, M. L.

    1999-09-01

    The Astronomy Workshop (http://janus.astro.umd.edu) is an interactive online astronomy resource developed and maintained at the University of Maryland for use by students, educators and the general public. The Astronomy Workshop has been extensively tested and used successfully at many different levels, including High School and Junior High School science classes, University introductory astronomy courses, and University intermediate and advanced astronomy courses. Some topics currently covered in the Astronomy Workshop are: Animated Orbits of Planets and Moons: The orbits of the nine planets and 63 known planetary satellites are shown in animated, to-scale drawings. The orbiting bodies move at their correct relative speeds about their parent, which is rendered as an attractive, to-scale gif image. Solar System Collisions: This most popular of our applications shows what happens when an asteroid or comet with user-defined size and speed impacts a given planet. The program calculates many effects, including the country impacted (if Earth is the target), energy of explosion, crater size, and magnitude of the ``planetquake'' generated. It also displays a relevant image (e.g. terrestrial crater, lunar crater, etc.). Scale of the Universe: Travel away from the Earth at a chosen speed and see how long it takes to reach other planets, stars and galaxies. This tool helps students visualize astronomical distances in an intuitive way. Scientific Notation: Students are interactively guided through conversions between scientific notation and regular numbers. Orbital Simulations: These tools allow the student to investigate different aspects of the three-body problem of celestial mechanics. Astronomy Workshop Bulletin Board: Get innovative teaching ideas and read about in-class experiences with the Astronomy Workshop. Share your ideas with other educators by posting on the Bulletin Board. Funding for the Astronomy Workshop is provided by NSF.

  1. The Astronomy Workshop

    NASA Astrophysics Data System (ADS)

    Hamilton, D. P.; Asbury, M. L.; Proctor, A.

    2001-12-01

    The Astronomy Workshop (http://janus.astro.umd.edu) is an interactive online astronomy resource developed, and maintained at the University of Maryland, for use by students, educators and the general public. The Astronomy Workshop has been extensively tested and used successfully at many different levels, including High School and Junior High School science classes, University introductory astronomy courses, and University intermediate and advanced astronomy courses. Some topics currently covered in the Astronomy Workshop are: Animated Orbits of Planets and Moons: The orbits of the nine planets and 91 known planetary satellites are shown in animated, to-scale drawings. The orbiting bodies move at their correct relative speeds about their parent, which is rendered as an attractive, to-scale gif image. Solar System Collisions: This most popular of our applications shows what happens when an asteroid or comet with user-defined size and speed impacts a given planet. The program calculates many effects, including the country impacted (if Earth is the target), energy of the explosion, crater size, magnitude of the planetquake generated. It also displays a relevant image (e.g. terrestrial crater, lunar crater, etc.). Planetary and Satellite Data Calculators: These tools allow the user to easily calculate physical data for all of the planets or satellites simultaneously, making comparison very easy. Orbital Simulations: These tools allow the student to investigate different aspects of the three-body problem of celestial mechanics. Astronomy Workshop Bulletin Board: Get innovative teaching ideas and read about in-class experiences with the Astronomy Workshop. Share your ideas with other educators by posting on the Bulletin Board. Funding for the Astronomy Workshop is provided by the National Science Foundation.

  2. The Astronomy Workshop

    NASA Astrophysics Data System (ADS)

    Hamilton, D. P.; Asbury, M. L.

    2000-05-01

    The Astronomy Workshop (http://janus.astro.umd.edu) is an interactive online astronomy resource developed and maintained at the University of Maryland for use by students, educators and the general public. The Astronomy Workshop has been extensively tested and used successfully at many different levels, including High School and Junior High School science classes, University introductory astronomy courses, and University intermediate and advanced astronomy courses. Some topics currently covered in the Astronomy Workshop are: ANIMATED ORBITS OF PLANETS AND MOONS: The orbits of the nine planets and 63 known planetary satellites are shown in animated, to-scale drawings. The orbiting bodies move at their correct relative speeds about their parent, which is rendered as an attractive, to-scale gif image. SOLAR SYSTEM COLLISIONS: This most popular of our applications shows what happens when an asteroid or comet with user-defined size and speed impacts a given planet. The program calculates many effects, including the country impacted (if Earth is the target), energy of explosion, crater size, and magnitude of the ``planetquake'' generated. It also displays a relevant image (e.g. terrestrial crater, lunar crater, etc.). SCALE OF THE UNIVERSE: Travel away from the Earth at a chosen speed and see how long it takes to reach other planets, stars and galaxies. This tool helps students visualize astronomical distances in an intuitive way. SCIENTIFIC NOTATION: Students are interactively guided through conversions between scientific notation and regular numbers. ORBITAL SIMULATIONS: These tools allow the student to investigate different aspects of the three-body problem of celestial mechanics. ASTRONOMY WORKSHOP BULLETIN BOARD: Get innovative teaching ideas and read about in-class experiences with the Astronomy Workshop. Share your ideas with other educators by posting on the Bulletin Board. Funding for the Astronomy Workshop is provided by NSF.

  3. The Astronomy Workshop

    NASA Astrophysics Data System (ADS)

    Hamilton, D. P.; Asbury, M. L.

    1999-12-01

    The Astronomy Workshop (http://janus.astro.umd.edu) is an interactive online astronomy resource developed and maintained at the University of Maryland for use by students, educators and the general public. The Astronomy Workshop has been extensively tested and used successfully at many different levels, including High School and Junior High School science classes, University introductory astronomy courses, and University intermediate and advanced astronomy courses. Some topics currently covered in the Astronomy Workshop are: Animated Orbits of Planets and Moons: The orbits of the nine planets and 63 known planetary satellites are shown in animated, to-scale drawings. The orbiting bodies move at their correct relative speeds about their parent, which is rendered as an attractive, to-scale gif image. Solar System Collisions: This most popular of our applications shows what happens when an asteroid or comet with user-defined size and speed impacts a given planet. The program calculates many effects, including the country impacted (if Earth is the target), energy of explosion, crater size, and magnitude of the ``planetquake'' generated. It also displays a relevant image (e.g. terrestrial crater, lunar crater, etc.). Scale of the Universe: Travel away from the Earth at a chosen speed and see how long it takes to reach other planets, stars and galaxies. This tool helps students visualize astronomical distances in an intuitive way. Scientific Notation: Students are interactively guided through conversions between scientific notation and regular numbers. Orbital Simulations: These tools allow the student to investigate different aspects of the three-body problem of celestial mechanics. Astronomy Workshop Bulletin Board: Get innovative teaching ideas and read about in-class experiences with the Astronomy Workshop. Share your ideas with other educators by posting on the Bulletin Board. Funding for the Astronomy Workshop is provided by NSF.

  4. Genesis of a workshop

    NASA Astrophysics Data System (ADS)

    Bourgeois, François

    2015-11-01

    The LHC Electronics Review Board was created in 1994 to advise the LHC experiments Committee LHCC on rationalization measures in the fields of design, manufacture and operation of electronic systems for LHC experiments. To this end, the LERB found appropriate to launch a series of topical workshops in order to allow for open discussions on the issues at stake. This paper recalls related events and decisions that occurred between 1985 and the approval of the LHC in 1995. The LERB terms of reference and the outcome of the first workshop are presented.

  5. Magnetic Suspension Technology Workshop

    NASA Technical Reports Server (NTRS)

    Keckler, Claude R. (Editor); Groom, Nelson J. (Editor); Britcher, Colin P. (Editor)

    1993-01-01

    In order to identify the state of magnetic suspension technology in such areas as rotating systems, pointing of experiments or subsystems, payload isolation, and superconducting materials, a workshop on Magnetic Suspension Technology was held at the Langley Research Center in Hampton, Virginia, on 2-4 Feb. 1988. The workshop included five technical sessions in which a total of 24 papers were presented. The technical sessions covered the areas of pointing, isolation, and measurement, rotating systems, modeling and control, and superconductors. A list of attendees is provided.

  6. Production of a recombinant capsid protein VP1 from a newly described polyomavirus (RacPyV) for downstream use in virus characterization.

    PubMed

    Church, Molly E; Dela Cruz, Florante N; Kim, Kevin; Persiani, Michele; Woods, Leslie W; Pesavento, Patricia A; Woolard, Kevin D

    2016-06-01

    Here we describe the methods for production of a recombinant viral capsid protein and subsequent use in an indirect enzyme linked immunosorbent assay (ELISA), and for use in production of a rabbit polyclonal antibody. These reagents were utilized in development and optimization of an ELISA, which established the extent of exposure of free ranging raccoons to a newly described polyomavirus (RacPyV) [1]. Production of a polyclonal antibody has allowed for further characterization of RacPyV, including immunohistochemistry and immunocytochemistry techniques, in order to answer questions about pathogenesis of this virus. PMID:26955649

  7. New Perspectives on Human Problem Solving

    ERIC Educational Resources Information Center

    Goldstone, Robert L.; Pizlo, Zygmunt

    2009-01-01

    In November 2008 at Purdue University, the 2nd Workshop on Human Problem Solving was held. This workshop, which was a natural continuation of the first workshop devoted almost exclusively to optimization problems, addressed a wider range of topics that reflect the scope of the "Journal of Problem Solving." The workshop was attended by 35…

  8. Preventive Maintenance Workshop.

    ERIC Educational Resources Information Center

    Ontario Ministry of the Environment, Toronto.

    This manual was developed for use at workshops designed to upgrade the knowledge of experienced water and wastewater treatment plant operators. The course consists of lecture-discussions and hands-on activities. Each of the lessons has clearly stated behavioral objectives to tell the trainee what he should know or do after completing a topic.…

  9. Fourth Airborne Geoscience Workshop

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The focus of the workshop was on how the airborne community can assist in achieving the goals of the Global Change Research Program. The many activities that employ airborne platforms and sensors were discussed: platforms and instrument development; airborne oceanography; lidar research; SAR measurements; Doppler radar; laser measurements; cloud physics; airborne experiments; airborne microwave measurements; and airborne data collection.

  10. Physics Teachers Workshop

    SciTech Connect

    Huggins, DaNel; Calhoun, John; Palmer, Alyson; Thorpe, Steve; Vanderveen, Anne

    2011-01-01

    INL is looking for the nation's top high school physics teachers to attend our July workshop in Idaho Falls. Participants get to learn from nuclear researchers, tour facilities including a research reactor and interact with peers from across the country. You can learn more about INL projects at http://www.facebook.com/idahonationallaboratory

  11. Space Processing Workshop

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Gravitational effects on electrodeposition were studied on the KC-135 aircraft parabolic flight paths. An experiment to investigate the effect of the hyperthermal atomic oxygen atmosphere on sensitive surfaces was flown on Space Shuttle Flight STS-18. A participant list and schedule for the Fluids Experiment System (FES) Workshop are given.

  12. Child Nutrition. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Hayden, Jacqueline; Eastman, Wayne; Aird, Laura Dutil; McCrea, Nadine L.

    2002-01-01

    Four workshops focus on nutrition for infants and children in child care settings. Articles are: (1) "Nutrition and Child Development: Global Perspectives" (Jacqueline Hayden); (2) "Working with Families around Nutritional Issues" (Wayne Eastman); (3) "Breastfeeding Promotion in Child Care" (Laura Dutil Aird); and (4) "Food as Shared…

  13. World without Workshops.

    ERIC Educational Resources Information Center

    Winkley, William M.

    1985-01-01

    The author examines the history of segregation for blind and handicapped persons and the relationship of segregation to social attitudes and opportunities. He also questions the relevance of sheltered workshops today. The El Paso Lighthouse "enclave with industry" program is presented as one model for moving toward a "natural proportion"…

  14. Pump Operation Workshop.

    ERIC Educational Resources Information Center

    Ontario Ministry of the Environment, Toronto.

    This manual was developed for use at workshops designed as an extension of training for water and wastewater treatment personnel. The course consists of lecture-discussions and hands-on activities. Each of the lessons in this document has clearly stated behavioral objectives to tell the trainee what he should know or do after completing that…

  15. Writing Workshop in Preschool

    ERIC Educational Resources Information Center

    King, Kelly A.

    2012-01-01

    Preschoolers may be novices in the area of writing but, as this article highlights, they are indeed writers. In a year-long ethnography of preschoolers during structured writing time the teacher/researcher explored how students adapted to a writing workshop format. Students participated in daily journal writing and sharing, and weekly conference…

  16. Radiation Source Replacement Workshop

    SciTech Connect

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

  17. Microwave Workshop for Windows.

    ERIC Educational Resources Information Center

    White, Colin

    1998-01-01

    "Microwave Workshop for Windows" consists of three programs that act as teaching aid and provide a circuit design utility within the field of microwave engineering. The first program is a computer representation of a graphical design tool; the second is an accurate visual and analytical representation of a microwave test bench; the third is a more…

  18. Dynamic defense workshop :

    SciTech Connect

    Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.

    2013-02-01

    On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-art work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.

  19. Flywheel energy storage workshop

    SciTech Connect

    O`Kain, D.; Carmack, J.

    1995-12-31

    Since the November 1993 Flywheel Workshop, there has been a major surge of interest in Flywheel Energy Storage. Numerous flywheel programs have been funded by the Advanced Research Projects Agency (ARPA), by the Department of Energy (DOE) through the Hybrid Vehicle Program, and by private investment. Several new prototype systems have been built and are being tested. The operational performance characteristics of flywheel energy storage are being recognized as attractive for a number of potential applications. Programs are underway to develop flywheels for cars, buses, boats, trains, satellites, and for electric utility applications such as power quality, uninterruptible power supplies, and load leveling. With the tremendous amount of flywheel activity during the last two years, this workshop should again provide an excellent opportunity for presentation of new information. This workshop is jointly sponsored by ARPA and DOE to provide a review of the status of current flywheel programs and to provide a forum for presentation of new flywheel technology. Technology areas of interest include flywheel applications, flywheel systems, design, materials, fabrication, assembly, safety & containment, ball bearings, magnetic bearings, motor/generators, power electronics, mounting systems, test procedures, and systems integration. Information from the workshop will help guide ARPA & DOE planning for future flywheel programs. This document is comprised of detailed viewgraphs.

  20. Dance Education Workshop

    ERIC Educational Resources Information Center

    Hanna, Judith Lynne

    2002-01-01

    Dance education in the USA has a new window of opportunity to reach every child in academic schools. The National Education Goals now recognize dance as a core subject, such as, e.g. language. To take advantage of this development, the "Intelligent Moves--Partnering Dance & Education K-12" workshop for teachers was held as part of the Vail Valley…

  1. Adolescent Development: Workshop II.

    ERIC Educational Resources Information Center

    Keng, Chiam Heng; And Others

    Workshops concerning adolescent development explored problems of adolescents, schooling and adolescence, preparation for adulthood, leisure and recreation, as well as values, culture, and change in relation to the development of youth. The discussion of adolescents' problems identified major problem areas, (emphasizing problems of communicating…

  2. Workshop on Molecular Evolution

    NASA Technical Reports Server (NTRS)

    Cummings, Michael P.

    2004-01-01

    Molecular evolution has become the nexus of many areas of biological research. It both brings together and enriches such areas as biochemistry, molecular biology, microbiology, population genetics, systematics, developmental biology, genomics, bioinformatics, in vitro evolution, and molecular ecology. The Workshop provides an important contribution to these fields in that it promotes interdisciplinary research and interaction, and thus provides a glue that sticks together disparate fields. Due to the wide range of fields addressed by the study of molecular evolution, it is difficult to offer a comprehensive course in a university setting. It is rare for a single institution to maintain expertise in all necessary areas. In contrast, the Workshop is uniquely able to provide necessary breadth and depth by utilizing a large number of faculty with appropriate expertise. Furthermore, the flexible nature of the Workshop allows for rapid adaptation to changes in the dynamic field of molecular evolution. For example, the 2003 Workshop included recently emergent research areas of molecular evolution of development and genomics.

  3. Workshop on Cosmogenic Nuclides

    NASA Technical Reports Server (NTRS)

    Reedy, R. C. (Editor); Englert, P. (Editor)

    1986-01-01

    Abstracts of papers presented at the Workshop on Cosmogenic Nuclides are compiled. The major topic areas covered include: new techniques for measuring nuclides such as tandem accelerator and resonance mass spectrometry; solar modulation of cosmic rays; pre-irradiation histories of extraterrestrial materials; terrestrial studies; simulations and cross sections; nuclide production rate calculations; and meteoritic nuclides.

  4. Parent Conferences. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Duffy, Roslyn; And Others

    1997-01-01

    Presents six workshop sessions on parent conferences: (1) "Parents' Perspectives on Conferencing" (R. Duffy); (2) "Three Way Conferences" (G. Zeller); (3) "Conferencing with Parents of Infants" (K. Albrecht); (4) "Conferencing with Parents of School-Agers" (L. G. Miller); (5) "Cross Cultural Conferences" (J. Gonzalez-Mena); and (6) "Working with…

  5. Polar Ozone Workshop. Abstracts

    NASA Technical Reports Server (NTRS)

    Aikin, Arthur C.

    1988-01-01

    Results of the proceedings of the Polar Ozone Workshop held in Snowmass, CO, on May 9 to 13, 1988 are given. Topics covered include ozone depletion, ozonometry, polar meteorology, polar stratospheric clouds, remote sensing of trace gases, atmospheric chemistry and dynamical simulations.

  6. Mentoring. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Scallan-Berl, Patricia; Moguil, Leslie; Nyman, Sessy I.; Mercado, Miriam Mercado

    2003-01-01

    This workshop presents information on mentoring relationships within child care settings. Articles are: (1) "Mentoring Teachers...A Partnership in Learning" (Patricia Scallan-Berl); (2) "The Potential Gains of Peer Mentoring among Children" (Leslie Moguil); (3) "Mentoring Advocates in the Context of Early Childhood Education" (Sessy Nyman); and…

  7. African Outreach Workshop 1974.

    ERIC Educational Resources Information Center

    Schmidt, Nancy J.

    This report discusses the 1974 African Outreach Workshop planned and coordinated by the African Studies Program at the University of Illinois at Urbana-Champaign. Its major aim was to assist teachers in developing curriculum units on African using materials available in their local community. A second aim was for the African Studies Program to…

  8. Physics Teachers Workshop

    ScienceCinema

    Huggins, DaNel; Calhoun, John; Palmer, Alyson; Thorpe, Steve; Vanderveen, Anne

    2016-07-12

    INL is looking for the nation's top high school physics teachers to attend our July workshop in Idaho Falls. Participants get to learn from nuclear researchers, tour facilities including a research reactor and interact with peers from across the country. You can learn more about INL projects at http://www.facebook.com/idahonationallaboratory

  9. Synthetic Vision Workshop 2

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J. (Compiler)

    1999-01-01

    The second NASA sponsored Workshop on Synthetic/Enhanced Vision (S/EV) Display Systems was conducted January 27-29, 1998 at the NASA Langley Research Center. The purpose of this workshop was to provide a forum for interested parties to discuss topics in the Synthetic Vision (SV) element of the NASA Aviation Safety Program and to encourage those interested parties to participate in the development, prototyping, and implementation of S/EV systems that enhance aviation safety. The SV element addresses the potential safety benefits of synthetic/enhanced vision display systems for low-end general aviation aircraft, high-end general aviation aircraft (business jets), and commercial transports. Attendance at this workshop consisted of about 112 persons including representatives from industry, the FAA, and other government organizations (NOAA, NIMA, etc.). The workshop provided opportunities for interested individuals to give presentations on the state of the art in potentially applicable systems, as well as to discuss areas of research that might be considered for inclusion within the Synthetic Vision Element program to contribute to the reduction of the fatal aircraft accident rate. Panel discussions on topical areas such as databases, displays, certification issues, and sensors were conducted, with time allowed for audience participation.

  10. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    PubMed

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction. PMID:25703592

  11. BrainMap `95 workshop

    SciTech Connect

    1995-12-31

    The fourth annual BrainMap workshop was held at La Mansion del Rio Hotel in San Antonio December 3--4, 1995. The conference title was ``Human Brain Mapping and Modeling.`` The meeting was attended by 137 registered participants and 30 observers from 82 institutions representing 12 countries. The meeting focused on the technical issues associated with brain mapping and modeling. A total of 23 papers were presented covering the following topics: spatial normalization and registration; functional image analysis; metanalysis and modeling; and new horizons in biological databases. The full program with abstracts was available on the Research Imaging Center`s web site. A book will be published by John Wiley and Sons prior to the end of 1998.

  12. International workshop of chromosome 19

    SciTech Connect

    Pericak-Vance, M.A. . Div. of Neurology); Carrano, A.J. )

    1991-09-16

    This document summarizes the workshop on physical and genetic mapping of chromosome 19. The first session discussed the major disease loci found on the chromosome. The second session concentrated on reference families, markers and linkage maps. The third session concentrated on radiation hybrid mapping, somatic cell hybrid panels, macro restriction maps and YACs, followed by cDNA and long range physical maps. The fourth session concentrated on compiling consensus genetic and physical maps as well as discussing regions of conflict. The final session dealt with the LLNL cosmid contig database and comparative mapping of homologous regions of the human and mouse genomes, and ended with a discussion of resource sharing. 18 refs., 2 figs. (MHB)

  13. Inter- and Intralaboratory Comparison of JC Polyomavirus Antibody Testing Using Two Different Virus-Like Particle-Based Assays

    PubMed Central

    Kardas, Piotr; Sadeghi, Mohammadreza; Weissbach, Fabian H.; Chen, Tingting; Hedman, Lea; Auvinen, Eeva; Hedman, Klaus

    2014-01-01

    JC polyomavirus (JCPyV) can cause progressive multifocal leukoencephalopathy (PML), a debilitating, often fatal brain disease in immunocompromised patients. JCPyV-seropositive multiple sclerosis (MS) patients treated with natalizumab have a 2- to 10-fold increased risk of developing PML. Therefore, JCPyV serology has been recommended for PML risk stratification. However, different antibody tests may not be equivalent. To study intra- and interlaboratory variability, sera from 398 healthy blood donors were compared in 4 independent enzyme-linked immunoassay (ELISA) measurements generating >1,592 data points. Three data sets (Basel1, Basel2, and Basel3) used the same basic protocol but different JCPyV virus-like particle (VLP) preparations and introduced normalization to a reference serum. The data sets were also compared with an independent method using biotinylated VLPs (Helsinki1). VLP preadsorption reducing ≥35% activity was used to identify seropositive sera. The results indicated that Basel1, Basel2, Basel3, and Helsinki1 were similar regarding overall data distribution (P = 0.79) and seroprevalence (58.0, 54.5, 54.8, and 53.5%, respectively; P = 0.95). However, intra-assay intralaboratory comparison yielded 3.7% to 12% discordant results, most of which were close to the cutoff (0.080 < optical density [OD] < 0.250) according to Bland-Altman analysis. Introduction of normalization improved overall performance and reduced discordance. The interlaboratory interassay comparison between Basel3 and Helsinki1 revealed only 15 discordant results, 14 (93%) of which were close to the cutoff. Preadsorption identified specificities of 99.44% and 97.78% and sensitivities of 99.54% and 95.87% for Basel3 and Helsinki1, respectively. Thus, normalization to a preferably WHO-approved reference serum, duplicate testing, and preadsorption for samples around the cutoff may be necessary for reliable JCPyV serology and PML risk stratification. PMID:25253664

  14. Progressive renal failure due to renal infiltration by BK polyomavirus and leukaemic cells: which is the culprit?

    PubMed

    Sangala, Nicholas; Dewdney, Alex; Marley, Nicholas; Cranfield, Tanya; Venkat-Raman, Gopalakrishnan

    2011-02-01

    Renal infiltration with leukaemic cells is a common finding in patients suffering with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft failure in renal transplant recipients but rarely causes significant disease in native kidneys. In the few reports where leukaemic infiltration of the kidney has led to significant renal impairment, the pathological process causing renal dysfunction is not identified on biopsy. In these cases, it is unclear whether BK polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual pathologies in a patient with Binet stage C CLL and deteriorating renal function where renal biopsy reveals leukaemic infiltration of the kidney occurring alongside BKV nephropathy. The relative importance of each pathology in relation to the rapid decline to end-stage renal failure remains unclear, but the presence of both pathologies appears to impart a poor prognosis. Additionally, we describe the novel histological finding of loss of tubular integrity resulting in tubular infiltration and occlusion by leukaemic cells. It is possible that the patient with advanced CLL is at particular risk of BK activation, and the presence of BK nephropathy may compromise tubular integrity allowing leukaemic cell infiltration and obstruction of tubules. This case bares remarkable resemblance to the first and only other report of its kind in the literature. It is not clear how available immunocytochemistry for polyoma infection is outside transplant centres, and it is possible that BK nephropathy is being under-diagnosed in patients with CLL in the context of declining renal function. At present, the combination of BKV nephropathy and leukaemic infiltration represents a management conundrum and the prognosis is poor. Further research is required in order to better understand the pathological process and therefore develop management strategies.

  15. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication.

    PubMed

    Schmidt, T; Adam, C; Hirsch, H H; Janssen, M W W; Wolf, M; Dirks, J; Kardas, P; Ahlenstiel-Grunow, T; Pape, L; Rohrer, T; Fliser, D; Sester, M; Sester, U

    2014-06-01

    BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during childhood, but may cause nephropathy in kidney transplant recipients. However, there is only limited knowledge on BKPyV-specific immunity in children and adults, and its role in BKPyV-replication and disease posttransplant. We therefore characterized BKPyV-specific immunity from 122 immunocompetent individuals (1-84 years), 38 adult kidney recipients with (n = 14) and without BKPyV-associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood samples were stimulated with overlapping peptides of BKPyV large-T antigen and VP1 followed by flow-cytometric analysis of activated CD4 T cells expressing interferon-γ, IL-2 and tumor necrosis factor-α. Antibody-levels were determined using enzyme-linked immunosorbent assay. Both BKPyV-IgG levels and BKPyV-specific CD4 T cell frequencies were age-dependent (p = 0.0059) with maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%). Transplant recipients showed a significantly higher BKPyV-specific T cell prevalence (57.9%) compared to age-matched controls (21.7%) or HD patients (28%, p = 0.017). Clinically relevant BKPyV-replication was associated with elevated frequencies of BKPyV-specific T cells (p = 0.0002), but decreased percentage of cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV-specific cellular immunity reflects phases of active BKPyV-replication either after primary infection in childhood or during reactivation after transplantation. Combined analysis of BKPyV-specific T cell functionality and viral loads may improve individual risk assessment.

  16. Correlation between DNA methyltransferases expression and Epstein-Barr virus, JC polyomavirus and Helicobacter pylori infections in gastric carcinomas.

    PubMed

    Ksiaa, F; Ziadi, S; Gacem, R B; Dhiab, M B; Trimeche, M

    2014-01-01

    It' is accepted that aberrant expression of DNA methyltransferases (DNMTs) is responsible for hypermethylation in genes. However, there are limited data related to factors inducing aberrant expression of DNMTs. A total of 43 surgically resected gastrc carcinomas (GC) samples were analysed. Using immunohistochemistry assay we have determined expression level of DNMT1 and 3b. The presence of H.pylori was evaluated by histology, whereas JC polyomavirus (JCV) and Epstein-Barr virus (EBV) detection were carried out by PCR and in situ hybridization techniques, respectively. High expression of DNMT1 and 3b were detected in 46.5% and 53.5% of GC cases, respectively. Co-expression of DNMT1 and 3b were found in 37.2% of cases. Using different techniques, H. pylori, JCV and EBV were detected in 55.8%, 32.6% and 9%, respectively. Moreover, in 37% of cases, we noted the presence of JCV and/or EBV infections. H.pylori co-infection was found in 64.3% (9/14) of JCV positive cases and in 50% of EBV positive GC, without a reliable significant relationship. Correlation analyses have showed a marked increase in DNMT1 expression in EBV associated GC (P= 0.02). Also, co-expression of DNMT1 and 3b was significantly associated with EBV infection in GC (P=0.05). Similarly, JCV associated GC mostly displayed DNMT1 positive status, but the difference did not reach the significant threshold. Nevertheless, infection with JCV and/or EBV was significantly correlated with increased expression of DNMT1 in GC (P= 0.05). Our study suggests that EBV and JCV infections in GC correlated with deregulation of DNA methyltransferases. PMID:25341997

  17. The Affording Mars Workshop: Background and Recommendations

    NASA Technical Reports Server (NTRS)

    Thronson, Harley A.; Carberry, Christopher

    2014-01-01

    A human mission to Mars is the stated "ultimate" goal for NASA and is widely believed by the public to be the most compelling destination for America's space program. However, widely cited enormous costs - perhaps as much as a trillion dollars for a many-decade campaign - seem to be an impossible hurdle, although political and budget instability over many years may be equally challenging. More recently, a handful of increasingly detailed architectures for initial Mars missions have been developed by commercial companies that have estimated costs much less than widely believed and roughly comparable with previous major human space flight programs: the Apollo Program, the International Space Station, and the space shuttle. Several of these studies are listed in the bibliography to the workshop report. As a consequence of these new scenarios, beginning in spring, 2013 a multiinstitutional planning team began developing the content and invitee list for a winter workshop that would critically assess concepts, initiatives, technology priorities, and programmatic options to reduce significantly the costs of human exploration of Mars. The output of the workshop - findings and recommendations - would be presented in a number of forums and discussed with national leaders in human space flight. It would also be made available to potential international partners. This workshop was planned from the start to be the first in a series. Subsequent meetings, conferences, and symposia will concentrate on topics not able to be covered in December. In addition, to make progress in short meeting, a handful of ground rules were adopted by the planning team and agreed to by the participants. Perhaps the two most notable such ground rules were (1) the Space Launch System (SLS) and Orion would be available during the time frame considered by the participants and (2) the International Space Station (ISS) would remain the early linchpin in preparing for Mars exploration over the coming decade

  18. UVI Cyber-security Workshop Workshop Analysis.

    SciTech Connect

    Kuykendall, Tommie G.; Allsop, Jacob Lee; Anderson, Benjamin Robert; Boumedine, Marc; Carter, Cedric; Galvin, Seanmichael Yurko; Gonzalez, Oscar; Lee, Wellington K.; Lin, Han Wei; Morris, Tyler Jake; Nauer, Kevin S.; Potts, Beth A.; Ta, Kim Thanh; Trasti, Jennifer; White, David R.

    2015-07-08

    The cybersecurity consortium, which was established by DOE/NNSA’s Minority Serving Institutions Partnerships Program (MSIPP), allows students from any of the partner schools (13 HBCUs, two national laboratories, and a public school district) to have all consortia options available to them, to create career paths and to open doors to DOE sites and facilities to student members of the consortium. As a part of this year consortium activities, Sandia National Laboratories and the University of Virgin Islands conducted a week long cyber workshop that consisted of three courses; Digital Forensics and Malware Analysis, Python Programming, and ThunderBird Cup. These courses are designed to enhance cyber defense skills and promote learning within STEM related fields.

  19. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells.

    PubMed

    Parolini, Ornella; Alviano, Francesco; Bagnara, Gian Paolo; Bilic, Grozdana; Bühring, Hans-Jörg; Evangelista, Marco; Hennerbichler, Simone; Liu, Bing; Magatti, Marta; Mao, Ning; Miki, Toshio; Marongiu, Fabio; Nakajima, Hideaki; Nikaido, Toshio; Portmann-Lanz, C Bettina; Sankar, Venkatachalam; Soncini, Maddalena; Stadler, Guido; Surbek, Daniel; Takahashi, Tsuneo A; Redl, Heinz; Sakuragawa, Norio; Wolbank, Susanne; Zeisberger, Steffen; Zisch, Andreas; Strom, Stephen C

    2008-02-01

    Placental tissue draws great interest as a source of cells for regenerative medicine because of the phenotypic plasticity of many of the cell types isolated from this tissue. Furthermore, placenta, which is involved in maintaining fetal tolerance, contains cells that display immunomodulatory properties. These two features could prove useful for future cell therapy-based clinical applications. Placental tissue is readily available and easily procured without invasive procedures, and its use does not elicit ethical debate. Numerous reports describing stem cells from different parts of the placenta, using nearly as numerous isolation and characterization procedures, have been published. Considering the complexity of the placenta, an urgent need exists to define, as clearly as possible, the region of origin and methods of isolation of cells derived from this tissue. On March 23-24, 2007, the first international Workshop on Placenta Derived Stem Cells was held in Brescia, Italy. Most of the research published in this area focuses on mesenchymal stromal cells isolated from various parts of the placenta or epithelial cells isolated from amniotic membrane. The aim of this review is to summarize and provide the state of the art of research in this field, addressing aspects such as cell isolation protocols and characteristics of these cells, as well as providing preliminary indications of the possibilities for use of these cells in future clinical applications. PMID:17975221

  20. 76 FR 52954 - Workshop: Advancing Research on Mixtures; New Perspectives and Approaches for Predicting Adverse...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Workshop: Advancing Research on Mixtures; New Perspectives and Approaches for Predicting... ``Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health...

  1. Magnet measurement workshop

    SciTech Connect

    1986-12-01

    This report covers the deliberations of the participants the workshop and some subsequent contributions. Section III, the report of the rotating coil group, includes a summary table of the major measuring systems in use today, with separate sections on each. Section IV is the summary report of the group that addressed other measuring techniques. Because one of the limits of all the techniques being considered is electronic data acquisition, Section V addresses this topic. A set of issues relevant to magnetic field measurements of SSC dipoles was raised and addressed during the workshop. These are included as Section VI. Section VII includes a complete list of attendees with their addresses and a separate list of the members of the two working groups.

  2. Rayleigh Scattering Diagnostics Workshop

    NASA Technical Reports Server (NTRS)

    Seasholtz, Richard (Compiler)

    1996-01-01

    The Rayleigh Scattering Diagnostics Workshop was held July 25-26, 1995 at the NASA Lewis Research Center in Cleveland, Ohio. The purpose of the workshop was to foster timely exchange of information and expertise acquired by researchers and users of laser based Rayleigh scattering diagnostics for aerospace flow facilities and other applications. This Conference Publication includes the 12 technical presentations and transcriptions of the two panel discussions. The first panel was made up of 'users' of optical diagnostics, mainly in aerospace test facilities, and its purpose was to assess areas of potential applications of Rayleigh scattering diagnostics. The second panel was made up of active researchers in Rayleigh scattering diagnostics, and its purpose was to discuss the direction of future work.

  3. Mars Surface Mission Workshop

    NASA Technical Reports Server (NTRS)

    Duke, M. B. (Editor)

    1997-01-01

    A workshop was held at the Lunar and Planetary Institute on September 4-5, 1997, to address the surface elements of the Mars Reference Mission now being reviewed by NASA. The workshop considered the current reference mission and addressed the types of activities that would be expected for science and resource exploration and facilities operations. A set of activities was defined that can be used to construct "vignettes" of the surface mission. These vignettes can form the basis for describing the importance of the surface mission, for illustrating aspects of the surface mission, and for allowing others to extend and revise these initial ideas. The topic is rich with opportunities for additional conceptualization. It is recommended that NASA consider supporting university design teams to conduct further analysis of the possibilities.

  4. Modified Composite Materials Workshop

    NASA Technical Reports Server (NTRS)

    Dicus, D. L. (Compiler)

    1978-01-01

    The reduction or elimination of the hazard which results from accidental release of graphite fibers from composite materials was studied at a workshop. At the workshop, groups were organized to consider six topics: epoxy modifications, epoxy replacement, fiber modifications, fiber coatings and new fibers, hybrids, and fiber release testing. Because of the time required to develop a new material and acquire a design data base, most of the workers concluded that a modified composite material would require about four to five years of development and testing before it could be applied to aircraft structures. The hybrid working group considered that some hybrid composites which reduce the risk of accidental fiber release might be put into service over the near term. The fiber release testing working group recommended a coordinated effort to define a suitable laboratory test.

  5. (Acid rain workshop)

    SciTech Connect

    Turner, R.S.

    1990-12-05

    The traveler presented a paper entitled Susceptibility of Asian Ecosystems to Soil-Mediated Acid Rain Damage'' at the Second Workshop on Acid Rain in Asia. The workshop was organized by the Asian Institute of Technology (Bangkok, Thailand), Argonne National Laboratory (Argonne, Illinois), and Resource Management Associates (Madison, Wisconsin) and was sponsored by the US Department of Energy, the United Nations Environment Program, the United Nations Economic and Social Commission for Asia and the Pacific, and the World Bank. Papers presented on the first day discussed how the experience gained with acid rain in North America and Europe might be applied to the Asian situation. Papers describing energy use projections, sulfur emissions, and effects of acid rain in several Asian countries were presented on the second day. The remaining time was allotted to discussion, planning, and writing plans for a future research program.

  6. Composites Damage Tolerance Workshop

    NASA Technical Reports Server (NTRS)

    Gregg, Wayne

    2006-01-01

    The Composite Damage Tolerance Workshop included participants from NASA, academia, and private industry. The objectives of the workshop were to begin dialogue in order to establish a working group within the Agency, create awareness of damage tolerance requirements for Constellation, and discuss potential composite hardware for the Crew Launch Vehicle (CLV) Upper Stage (US) and Crew Module. It was proposed that a composites damage tolerance working group be created that acts within the framework of the existing NASA Fracture Control Methodology Panel. The working group charter would be to identify damage tolerance gaps and obstacles for implementation of composite structures into manned space flight systems and to develop strategies and recommendations to overcome these obstacles.

  7. PREFACE: Collapse Calderas Workshop

    NASA Astrophysics Data System (ADS)

    Gottsmann, Jo; Aguirre-Diaz, Gerardo

    2008-10-01

    Caldera-formation is one of the most awe-inspiring and powerful displays of nature's force. Resultant deposits may cover vast areas and significantly alter the immediate topography. Post-collapse activity may include resurgence, unrest, intra-caldera volcanism and potentially the start of a new magmatic cycle, perhaps eventually leading to renewed collapse. Since volcanoes and their eruptions are the surface manifestation of magmatic processes, calderas provide key insights into the generation and evolution of large-volume silicic magma bodies in the Earth's crust. Despite their potentially ferocious nature, calderas play a crucial role in modern society's life. Collapse calderas host essential economic deposits and supply power for many via the exploitation of geothermal reservoirs, and thus receive considerable scientific, economic and industrial attention. Calderas also attract millions of visitors world-wide with their spectacular scenic displays. To build on the outcomes of the 2005 calderas workshop in Tenerife (Spain) and to assess the most recent advances on caldera research, a follow-up meeting was proposed to be held in Mexico in 2008. This abstract volume presents contributions to the 2nd Calderas Workshop held at Hotel Misión La Muralla, Querétaro, Mexico, 19-25 October 2008. The title of the workshop `Reconstructing the evolution of collapse calderas: Magma storage, mobilisation and eruption' set the theme for five days of presentations and discussions, both at the venue as well as during visits to the surrounding calderas of Amealco, Amazcala and Huichapan. The multi-disciplinary workshop was attended by more than 40 scientist from North, Central and South America, Europe, Australia and Asia. Contributions covered five thematic topics: geology, geochemistry/petrology, structural analysis/modelling, geophysics, and hazards. The workshop was generously supported by the International Association of Volcanology and the Chemistry of The Earth's Interior

  8. Imaging Sciences Workshop Proceedings

    SciTech Connect

    Candy, J.V.

    1996-11-21

    This report contains the proceedings of the Imaging Sciences Workshop sponsored by C.A.S.LS., the Center for Advanced Signal & Image Sciences. The Center, established primarily to provide a forum where researchers can freely exchange ideas on the signal and image sciences in a comfortable intellectual environment, has grown over the last two years with the opening of a Reference Library (located in Building 272). The Technical Program for the 1996 Workshop include a variety of efforts in the Imaging Sciences including applications in the Microwave Imaging, highlighted by the Micro-Impulse Radar (MIR) system invented at LLNL, as well as other applications in this area. Special sessions organized by various individuals in Speech, Acoustic Ocean Imaging, Radar Ocean Imaging, Ultrasonic Imaging, and Optical Imaging discuss various applica- tions of real world problems. For the more theoretical, sessions on Imaging Algorithms and Computed Tomography were organized as well as for the more pragmatic featuring a session on Imaging Systems.

  9. Research needs to better understand Lake Ontario ecosystem function: A workshop summary

    USGS Publications Warehouse

    Stewart, Thomas J.; Rudstam, Lars G.; Watkins, James M.; Johnson, Timothy B.; Weidel, Brian C.; Koops, Marten A.

    2016-01-01

    Lake Ontario investigators discussed and interpreted published and unpublished information during two workshops to assess our current understanding of Lake Ontario ecosystem function and to identify research needs to guide future research and monitoring activities. The purpose of this commentary is to summarize key investigative themes and hypotheses that emerged from the workshops. The outcomes of the workshop discussions are organized under four themes: spatial linkages and interactions, drivers of primary production, trophic transfer, and human interactions.

  10. Interdisciplinary workshop in the philosophy of medicine: medical knowledge, medical duties

    PubMed Central

    Kingma, Elselijn

    2014-01-01

    Abstract On 27 September 2013, the Centre for the Humanities and Health (CHH) at King's College London hosted a 1‐day workshop on ‘Medical knowledge, Medical Duties’. This workshop was the fifth in a series of five workshops whose aim is to provide a new model for high‐quality, open interdisciplinary engagement between medical professionals and philosophers. This report identifies the key points of discussion raised throughout the day and the methodology employed. PMID:25470528

  11. Workshop II: Physics Education

    NASA Astrophysics Data System (ADS)

    Horton, Renee; Milner-Bolotin, Marina

    2015-12-01

    Participants in the Physics Education Workshop at the 5th IUPAP International Conference on Women in Physics heard about, among other topics, a study exploring why students have difficulty with concepts related to magnetism (and whether explicitly evoking gender affects the results), work in Europe to develop materials to help teachers implement inquiry-based science education, and the use of peer instruction and online collaboration to help teacher-candidates develop questioning skills.

  12. Workshop on Harmonic Oscillators

    NASA Technical Reports Server (NTRS)

    Han, D. (Editor); Kim, Y. S. (Editor); Zachary, W. W. (Editor)

    1993-01-01

    Proceedings of a workshop on Harmonic Oscillators held at the College Park Campus of the University of Maryland on March 25 - 28, 1992 are presented. The harmonic oscillator formalism is playing an important role in many branches of physics. This is the simplest mathematical device which can connect the basic principle of physics with what is observed in the real world. The harmonic oscillator is the bridge between pure and applied physics.

  13. Unmanned Aerospace Vehicle Workshop

    SciTech Connect

    Vitko, J. Jr.

    1995-04-01

    The Unmanned Aerospace Vehicle (UAV) Workshop concentrated on reviewing and refining the science experiments planned for the UAV Demonstration Flights (UDF) scheduled at the Oklahoma Cloud and Radiation Testbed (CART) in April 1994. These experiments were focused around the following sets of parameters: Clear sky, daylight; Clear-sky, night-to-day transition; Clear sky - improve/validate the accuracy of radiative fluxes derived from satellite-based measurements; Daylight, clouds of opportunity; and, Daylight, broken clouds.

  14. Imaging sciences workshop

    SciTech Connect

    Candy, J.V.

    1994-11-15

    This workshop on the Imaging Sciences sponsored by Lawrence Livermore National Laboratory contains short abstracts/articles submitted by speakers. The topic areas covered include the following: Astronomical Imaging; biomedical imaging; vision/image display; imaging hardware; imaging software; Acoustic/oceanic imaging; microwave/acoustic imaging; computed tomography; physical imaging; imaging algorithms. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  15. Discovery management workshop

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Two dozen participants assembled under the direction of the NASA Solar System Exploration Division (SEED) April 13-15, 1993. Participants supported the goals of cheaper and faster solar system exploration. The workshop concluded that the Discovery Program concept and goals are viable. Management concerns are articulated in the final report. Appendix A includes lists of participants in alphabetical order, by functional area, and by organization type. Appendix B includes the agenda for the meeting.

  16. The urban perspectives of acid rain. Workshop summary

    SciTech Connect

    Tonn, B.E.

    1993-06-04

    This report documents discussions held during a workshop an Urban Perspective of Acid Rain. The workshop was sponsored by the Office of the Director, National Acid Precipitation Assessment Program (NAPAP). NAPAP anticipates giving increased emphasis to the benefits in urban areas of emissions reductions. The goal of this informal, exploratory workshop was to serve as a first step towards identifying pollutant monitoring, and research and assessment needs to help answer, from an urban perspective, the two key questions posed to NAPAP by Congress: (1) what are the costs, benefits, and effectiveness of the acid rain control program, and (2) what reductions in deposition, rates are needed in order to prevent adverse effects? The workshop addressed research activities needed to respond to these questions. The discussions focused. sequentially, on data needs, data and model availability, and data and modeling gaps. The discussions concentrated on four areas of effects: human health, materials, urban forests, and visibility.

  17. Exozodiacal Dust Workshop

    NASA Technical Reports Server (NTRS)

    Backman, D. E. (Editor); Caroff, L. J. (Editor); Sandford, S. A. (Editor); Wooden, D. H. (Editor)

    1998-01-01

    The purpose of the workshop was to understand what effect circumstellar dust clouds will have on NASA's proposed Terrestrial Planet Finder (TPF) mission's ability to search for terrestrial-sized planets orbiting stars in the solar neighborhood. The workshop participants reviewed the properties of TPF, summarized what is known about the local zodiacal cloud and about exozodiacal clouds, and determined what additional knowledge must be obtained to help design TPF for maximum effectiveness within its cost constraint. Recommendations were made for ways to obtain that additional knowledge, at minimum cost. The workshop brought together approximately 70 scientists, from four different countries. The active participants included astronomers involved in the study of the local zodiacal cloud, in the formation of stars and planetary systems, and in the technologies and techniques of ground- and space-based infrared interferometry. During the course of the meeting, 15 invited talks and 20 contributed poster papers were presented, and there were four working sessions. This is a collection of the invited talks, contributed poster papers, and summaries of the working sessions.

  18. Marine Multichannel Seismology Workshop

    NASA Astrophysics Data System (ADS)

    Detrick, Bob

    1984-04-01

    The multichannel seismic (MCS) reflection technique, developed by the oil industry for petroleum exploration in sedimentary basins, has proven to be a powerful tool for imaging subsurface geology in a wide variety of tectonic settings at a scale suitable for detailed investigations of geological structures and processes. In the ocean basins, MCS studies have provided new insight into the tectonic history of rifted and convergent continental margins, the structure of the oceanic crust and midocean ridges, and the sedimentation history and paleoceanography of deep ocean basins. MCS techniques have thus developed into an important tool for marine geological and geophysical research.The National Science Foundation recently sponsored a Workshop on the Future of Academic Marine Multichannel Seismology in the United States, held in Boulder, Colo., on March 19-20, 1984, to review the current state of marine academic MCS in the United States and to make recommendations on the facilities and funding required to meet future scientific needs. The workshop, which was convened by Brian T.R. Lewis of the University of Washington, included 19 scientists representing the major U.S. oceanographic institutions with interests in marine seismic work. This article summarizes the major recommendations developed at this workshop, which have been included in a more comprehensive report entitled ‘A National Plan for Marine Multichannel Seismology,’ which has been submitted to the National Science Foundation for future publication.

  19. 2014 Penn State Bioinorganic Workshop

    SciTech Connect

    Golbeck, John

    2015-10-01

    The 3rd Penn State Bioinorganic Workshop took place in early June 2014 and was combined with the 3rd Penn State Frontiers in Metallobiochemistry Symposium. The workshop was even larger than the 2nd Penn State Bioinorganic Workshop we offered in 2012. It had even more participants (162 rather than 123 in 2012). Like the 2012 workshop, the 2014 workshop had three parts. The first part consisted of 16 90-minute lectures presented by faculty experts on the topic of their expertise (see below). Based on the suggestions from the 2012 workshop, we have recorded all 16 lectures professionally and make them available to the entire bioinorganic community via online streaming. In addition, hard copies of the recordings are available as backup.

  20. Proceedings of the 2013 A.S.P.E.N. Research workshop: the interface between nutrition and the gut microbiome: implications and applications for human health [corrected].

    PubMed

    Alverdy, John; Gilbert, Jack; DeFazio, Jennifer R; Sadowsky, Michael J; Chang, Eugene B; Morowitz, Michael J; Teitelbaum, Daniel H

    2014-02-01

    The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high-resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross-reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.-sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease. PMID:24379111

  1. Urban guideway transit workshop: Proceedings

    SciTech Connect

    Larsen, H. )

    1992-03-01

    On March 20--21, 1991, EPRI sponsored a workshop on urban guideway transit. The purpose of this workshop was to provide utility managers with increased knowledge about urban guideway transit options, public policy regarding transit, and the effect of transit options on utility operations. With this information utilities should be better prepared to make decisions about transit development in their service areas. The workshop also provided EPRI with ideas and information for developing an R D project plan for urban guideway transit.

  2. Workshop on Radio Transients

    NASA Astrophysics Data System (ADS)

    Croft, Steve; Gaensler, Bryan

    2012-04-01

    abstract-type="normal">SummaryWe are entering a new era in the study of variable and transient radio sources. This workshop discussed the instruments and the strategies employed to study those sources, how they are identified and classified, how results from different surveys can be compared, and how radio observations tie in with those at other wavelengths. The emphasis was on learning what common ground there is between the plethora of on-going projects, how methods and code can be shared, and how best practices regarding survey strategy could be adopted. The workshop featured the four topics below. Each topic commenced with a fairly brief introductory talk, which then developed into discussion. By way of preparation, participants had been invited to upload and discuss one slide per topic to a wiki ahead of the workshop. 1. Telescopes, instrumentation and survey strategy. New radio facilities and on-going projects (including upgrades) are both studying the variability of the radio sky, and searching for transients. The discussion first centred on the status of those facilities, and on projects with a time-domain focus, both ongoing and planned, before turning to factors driving choices of instrumentation, such as phased array versus single pixel feeds, the field of view, spatial and time resolution, frequency and bandwidth, depth, area, and cadence of the surveys. 2. Detection, pipelines, and classification. The workshop debated (a) the factors that influence decisions to study variability in the (u,v) plane, in images, or in catalogues, (b) whether, and how much, pipeline code could potentially be shared between one project and another, and which software packages are best for different approaches, (c) how data are stored and later accessed, and (d) how transients and variables are defined and classified. 3. Statistics, interpretation, and synthesis. It then discussed how (i) the choice of facility and strategy and (ii) detection and classification schemes

  3. Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

    PubMed Central

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future. PMID:26184314

  4. Optical Network Testbeds Workshop

    SciTech Connect

    Joe Mambretti

    2007-06-01

    This is the summary report of the third annual Optical Networking Testbed Workshop (ONT3), which brought together leading members of the international advanced research community to address major challenges in creating next generation communication services and technologies. Networking research and development (R&D) communities throughout the world continue to discover new methods and technologies that are enabling breakthroughs in advanced communications. These discoveries are keystones for building the foundation of the future economy, which requires the sophisticated management of extremely large qualities of digital information through high performance communications. This innovation is made possible by basic research and experiments within laboratories and on specialized testbeds. Initial network research and development initiatives are driven by diverse motives, including attempts to solve existing complex problems, the desire to create powerful new technologies that do not exist using traditional methods, and the need to create tools to address specific challenges, including those mandated by large scale science or government agency mission agendas. Many new discoveries related to communications technologies transition to wide-spread deployment through standards organizations and commercialization. These transition paths allow for new communications capabilities that drive many sectors of the digital economy. In the last few years, networking R&D has increasingly focused on advancing multiple new capabilities enabled by next generation optical networking. Both US Federal networking R&D and other national R&D initiatives, such as those organized by the National Institute of Information and Communications Technology (NICT) of Japan are creating optical networking technologies that allow for new, powerful communication services. Among the most promising services are those based on new types of multi-service or hybrid networks, which use new optical networking

  5. Mars Sample Quarantine Protocol Workshop

    NASA Technical Reports Server (NTRS)

    DeVincenzi, Donald L. (Editor); Bagby, John (Editor); Race, Margaret (Editor); Rummel, John (Editor)

    1999-01-01

    The Mars Sample Quarantine Protocol (QP) Workshop was convened to deal with three specific aspects of the initial handling of a returned Mars sample: 1) biocontainment, to prevent uncontrolled release of sample material into the terrestrial environment; 2) life detection, to examine the sample for evidence of live organisms; and 3) biohazard testing, to determine if the sample poses any threat to terrestrial life forms and the Earth's biosphere. During the first part of the Workshop, several tutorials were presented on topics related to the workshop in order to give all participants a common basis in the technical areas necessary to achieve the objectives of the Workshop.

  6. Life Support and Habitation and Planetary Protection Workshop

    NASA Technical Reports Server (NTRS)

    Hogan, John A. (Editor); Race, Margaret S. (Editor); Fisher, John W. (Editor); Joshi, Jitendra A. (Editor); Rummel, John D. (Editor)

    2006-01-01

    A workshop entitled "Life Support and Habitation and Planetary Protection Workshop" was held in Houston, Texas on April 27-29, 2005 to facilitate the development of planetary protection guidelines for future human Mars exploration missions and to identify the potential effects of these guidelines on the design and selection of related human life support, extravehicular activity and monitoring and control systems. This report provides a summary of the workshop organization, starting assumptions, working group results and recommendations. Specific result topics include the identification of research and technology development gaps, potential forward and back contaminants and pathways, mitigation alternatives, and planetary protection requirements definition needs. Participants concluded that planetary protection and science-based requirements potentially affect system design, technology trade options, development costs and mission architecture. Therefore early and regular coordination between the planetary protection, scientific, planning, engineering, operations and medical communities is needed to develop workable and effective designs for human exploration of Mars.

  7. NASA Breakthrough Propulsion Physics Workshop Proceedings

    NASA Technical Reports Server (NTRS)

    Millis, Marc G. (Editor); Williamson, Gary Scott (Editor)

    1999-01-01

    In August 1997, NASA sponsored a 3-day workshop to assess the prospects emerging from physics that may eventually lead to creating propulsion breakthroughs -the kind of breakthroughs that could revolutionize space flight and enable human voyages to other star systems. Experiments and theories were discussed regarding the coupling of gravity and electromagnetism, vacuum fluctuation energy, warp drives and wormholes, and superluminal quantum tunneling. Because the propulsion goals are presumably far from fruition, a special emphasis was to identify affordable, near-term, and credible research tasks that could make measurable progress toward these grand ambitions. This workshop was one of the first steps for the new NASA Breakthrough Propulsion Physics program led by the NASA Lewis Research Center.

  8. PD-L1 expression in the Merkel cell carcinoma microenvironment: Association with inflammation, Merkel cell polyomavirus and overall survival

    PubMed Central

    Loyo, Myriam; Kagohara, Luciane T.; Luber, Brandon S.; Wang, Hao; Xu, Haiying; Nayar, Suresh K.; Wang, Timothy S.; Sidransky, David; Anders, Robert A.; Topalian, Suzanne L.; Taube, Janis M.

    2013-01-01

    Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TILs), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1(+) tumor cells, 97% (28/29) demonstrated a geographic association with immune infiltrates. Among specimens with moderate-severe TIL intensities, 100% (29/29) demonstrated PD-L1 expression by tumor cells. Significant associations were also observed between the presence of MCPyV DNA, a brisk inflammatory response, and tumor cell PD-L1 expression: MCPyV(−) tumor cells were uniformly PD-L1(−). Taken together, these findings suggest that a local tumor-specific and potentially MCPyV-specific immune response drives tumor PD-L1 expression, similar to previous observations in melanoma and head and neck squamous cell carcinomas. In multivariate analyses, PD-L1(−) MCCs were independently associated with worse overall survival (hazard ratio 3.12; 95% CI, 1.28-7.61; p=0.012). These findings suggest that an endogenous immune response promotes PD-L1 expression in the MCC microenvironment when MCPyV is present, and provide a rationale for investigating therapies blocking PD-1/PD-L1 for patients with MCC. PMID:24416729

  9. RFI Mitigation Workshop

    NASA Astrophysics Data System (ADS)

    2010-05-01

    The increased sensitivity of passive instrumentation in radio astronomy and remote sensing and the intensifying active use of the spectrum have led to an increasing level of radio frequency interference (RFI) of the active services on the passive use of the spectrum. Advances in technology and computing have opened up new possibilities for mitigating the effects of certain classes of interference in the observing data. Interference in allocated bands always leads to data loss for the passive users of the spectrum even if interference mitigation is applied. However, interference mitigation in non-allocated spectral bands may facilitate the partial use of this spectrum for passive (non-interfering) observations. There is no generic method to mitigate all types of interference, so a multi-layered system approach may be advisable to reduce detrimental effects for a congested interference environment. Specific mitigation methods implemented at different points in the data acquisition chain will thus result in a cumulative mitigation effect on the data. This third RFI Mitigation Workshop considered RFI mitigation in radio astronomy in all its facets with the aim of facilitating the implementation of instrumental and data processing techniques. This workshop aimed to take a forward look at applications for the next generation of radio instruments, such as the SKA and its pathfinders and LOFAR, as well as considering their application to existing instruments. This workshop has been organized by ASTRON and NAIC, with support from the Engineering Forum of FP7 RadioNet, the SKA Project Development Office, and in collaboration with CRAF and IUCAF.

  10. 75 FR 42085 - Workshop To Review Initial Health Effects Draft Materials for the Ozone (O3

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... AGENCY Workshop To Review Initial Health Effects Draft Materials for the Ozone (O 3 ) Integrated Science... (O 3 ), EPA is announcing that a workshop to evaluate initial draft materials for the health effects... sections on the health effects evidence from in vivo and in vitro animal toxicology, human clinical,...

  11. 76 FR 42716 - Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-19

    ... HUMAN SERVICES Food and Drug Administration Effects of Ischemia Reperfusion Injury on Outcomes in Kidney... Food and Drug Administration (FDA) is announcing a public workshop to discuss the effects of ischemia... 7 days in advance. SUPPLEMENTARY INFORMATION: FDA is announcing a public workshop regarding...

  12. Workshop on Science and Technology Education and Productive Work. Final Report.

    ERIC Educational Resources Information Center

    Ministry of Education, Addis Ababa (Ethiopia).

    This workshop was organized as a contribution to Ethiopia's human resettlement activities necessitated by the recurrent drought. The objectives of the workshop were to: (1) appraise the relevance of basic rural technologies and identify modalities of their application; (2) develop materials in the fields of biotechnology and basic technology; (3)…

  13. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... HUMAN SERVICES Food and Drug Administration The Development and Evaluation of Next-Generation Smallpox... workshop entitled ``The Development and Evaluation of Next-Generation Smallpox Vaccines.'' The purpose of... evaluation of next-generation smallpox vaccines. The public workshop will include presentations on the...

  14. 78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... Globulin Infusions; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public... Address Hemolytic Complications of Immune Globulin Infusions.'' The purpose of the public workshop is to... complication of Immune Globulin Intravenous (IGIV) (Human) infusion. Complications of hemolysis include...

  15. 77 FR 14814 - Tobacco Product Analysis; Scientific Workshop; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... HUMAN SERVICES Food and Drug Administration Tobacco Product Analysis; Scientific Workshop; Request for.... The Food and Drug Administration (FDA), Center for Tobacco Products is announcing a scientific workshop to solicit feedback on analysis of tobacco products. The analyses of tobacco products...

  16. 78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Complex Issues in Developing Drug and Biological Products... announcing the following public workshop entitled ``Complex Issues in Developing Drug and Biological Products for Rare Diseases.'' The purpose of the public workshop is twofold: To discuss complex issues...

  17. 76 FR 17657 - Medical Device Epidemiology Network 2011: Second Annual Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ... HUMAN SERVICES Food and Drug Administration Medical Device Epidemiology Network 2011: Second Annual... Network (MDEpiNet) 2011: Second Annual Public Workshop.'' The purpose of the public workshop is to provide... establishment of a network that works with FDA experts to determine the evidence gaps and questions,...

  18. 77 FR 48160 - Division of Cardiovascular Devices 30-Day Notices and Annual Reports; Public Workshop; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-13

    ... HUMAN SERVICES Food and Drug Administration Division of Cardiovascular Devices 30-Day Notices and Annual... following public workshop entitled ``Division of Cardiovascular Devices 30-Day Notices and Annual Reports..., specifically for cardiovascular devices. DATES: Date and Time: The public workshop will be held on August...

  19. International workshop on chromosome 6. Final report, June 1, 1992--May 31, 1993

    SciTech Connect

    Trent, J.M.

    1994-02-01

    This report describes planning for and a brief description of the events concerning the First International Workshop in Human Chromosome 6 which took place June 7--9, 1992 in Ann Arbor, Michigan. The complete publication of the workshop report is slated to appear in the Journal of Cytogenetica and Cell Genetics.

  20. 78 FR 18611 - Summit on Color in Medical Imaging; Cosponsored Public Workshop; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ... HUMAN SERVICES Food and Drug Administration Summit on Color in Medical Imaging; Cosponsored Public... International Color Consortium (ICC) are announcing the following public workshop entitled ``Summit on Color in... Approaches for Dealing with Color in Medical Images.'' The purpose of the workshop is to bring together...

  1. 76 FR 34994 - Vaccine To Protect Children From Anthrax-Public Engagement Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... HUMAN SERVICES Vaccine To Protect Children From Anthrax--Public Engagement Workshop AGENCY: Office of... Biodefense Science Board's (NBSB) Anthrax Vaccine (AV) Working Group (WG) will hold a public engagement workshop on July 7, 2011, to discuss vaccine to protect children from anthrax. This meeting is open to...

  2. 76 FR 42715 - Quarantine Release Errors in Blood Establishments; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-19

    ... workshop has been planned in partnership with the Department of Health and Human Services (HHS) Office of the Assistant Secretary for Health, America's Blood Centers, and AABB. This public workshop will... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH...

  3. Melioidosis Diagnostic Workshop, 20131

    PubMed Central

    AuCoin, David; Baccam, Prasith; Baggett, Henry C.; Baird, Rob; Bhengsri, Saithip; Blaney, David D.; Brett, Paul J.; Brooks, Timothy J.G.; Brown, Katherine A.; Chantratita, Narisara; Cheng, Allen C.; Dance, David A.B.; Decuypere, Saskia; Defenbaugh, Dawn; Gee, Jay E.; Houghton, Raymond; Jorakate, Possawat; Lertmemongkolchai, Ganjana; Limmathurotsakul, Direk; Merlin, Toby L.; Mukhopadhyay, Chiranjay; Norton, Robert; Peacock, Sharon J.; Rolim, Dionne B.; Simpson, Andrew J.; Steinmetz, Ivo; Stoddard, Robyn A.; Stokes, Martha M.; Sue, David; Tuanyok, Apichai; Whistler, Toni; Wuthiekanun, Vanaporn; Walke, Henry T.

    2015-01-01

    Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions. PMID:25626057

  4. CENDI Indexing Workshop

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The CENDI Indexing Workshop held at NASA Headquarters, Two Independence Square, 300 E Street, Washington, DC, on September 21-22, 1994 focused on the following topics: machine aided indexing, indexing quality, an indexing pilot project, the MedIndEx Prototype, Department of Energy/Office of Scientific and Technical Information indexing activities, high-tech coding structures, category indexing schemes, and the Government Information Locator Service. This publication consists mostly of viewgraphs related to the above noted topics. In an appendix is a description of the Government Information Locator Service.

  5. Magnetoplasmadynamic Thruster Workshop

    NASA Technical Reports Server (NTRS)

    1991-01-01

    On May 16, 1991, the NASA Headquarters Propulsion, Power, and Energy Division and the NASA Lewis Research Center Low Thrust Propulsion Branch hosted a workshop attended by key experts in magnetoplasmadynamic (MPD) thrusters and associated sciences. The scope was limited to high power MPD thrusters suitable for major NASA space exploration missions, and its purpose was to initiate the process of increasing the expectations and prospects for MPD research, primarily by increasing the level of cooperation, interaction, and communication between parties within the MPD community.

  6. Space Weather Workshop

    NASA Technical Reports Server (NTRS)

    Gallagher, D. L.

    2004-01-01

    This workshop will focus on what space weather is about and its impact on society. An overall picture will be "painted" describing the Sun's influence through the solar wind on the near-Earth space environment, including the aurora, killer electrons at geosynchronous orbit, million ampere electric currents through the ionosphere and along magnetic field lines, and the generation of giga-Watts of natural radio waves. Reference material in the form of Internet sites will be provided so that teachers can discuss space weather in the classroom and enable students to learn more about this topic.

  7. Joint bone radiobiology workshop

    SciTech Connect

    Tomich, P.A.

    1991-01-01

    The Joint Bone Radiobiology Workshop was held on July 12--13, 1991 in Toronto, Canada. This document contains the papers presented at the meeting. The five sections were: Dose-effects, Endogenous Cofactors, Tumorigenesis, New Methods and Medical Implications. The papers covered risk assessment, tissue distribution of radionuclides, lifetime studies, biological half-lifes, the influence of age at time of exposure, tumor induction by different radionuclides, microscopic localization of radionuclides, and nuclear medicine issues including tissue distribution in the skeleton and bone marrow transplantation. (MHB)

  8. Image Registration Workshop Proceedings

    NASA Technical Reports Server (NTRS)

    LeMoigne, Jacqueline (Editor)

    1997-01-01

    Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research.

  9. Section workshop, field trips

    NASA Astrophysics Data System (ADS)

    McKnight, Diane

    The formation of a new Membership Committee to strengthen recruitment of members to the Biogeosciences Section was one of the outcomes of the “Biogeosciences on the Threshold” workshop held March 23-25, 2001. Eighteen biogeoscientists gathered near Baltimore, Maryland, to discuss future research themes, as well as the direction and structure of the new section.The Membership Committee is chaired by Max Holmes and will coordinate with AGU staff in recruiting scientists from the biogeosciences to join AGU. If you are interested in being involved in recruitment or have suggestions for groups to contact, please get in touch with Max Holmes (rholmes@mbl.edu).

  10. School Workshops on Astronomy

    NASA Astrophysics Data System (ADS)

    Molenda-Żakowicz, J.; Żakowicz, G.

    2015-03-01

    Do you want to know how to make students volunteer to stay all night long watching the stars with their telescopes freezing? Or how to inspire decent adults to prepare a `queue-list to Jupiter', wait for their turn for hours, and control that no one approaches the telescope bypassing the line? Or how to attract people of all age to forget their laziness and duties, and to get up at 3 a.m. to watch the transit of Venus? If your answer is `yes', then come and see what can be done at the School Workshops on Astronomy.

  11. Little meteorological workshop

    NASA Astrophysics Data System (ADS)

    Poler Čanić, K. Å.; Rasol, D.

    2010-09-01

    Little meteorological workshop (LMW) is a project the main goal of which is promotion and popularisation of meteorology in Croatia. The project has been taking place at the Science Festival in Zagreb since 2007 where the audience includes the general public. Since 2009 the project has been introduced as an extracurricular school activity in some primary schools where the main audience are children and teachers. Here, the methods used in the LMWs will be presented. Furthermore, the evaluation results of the LMWs that were held in schools will be shown.

  12. Martian Clouds Data Workshop

    NASA Technical Reports Server (NTRS)

    Lee, Steven (Editor)

    1987-01-01

    The major topics covered were a discussion of the structure of relational data base systems and features of the Britton Lee Relational Data Base Management System (RDBMS); a discussion of the workshop's objectives, approach, and research scenarios; and an overview of the Atmospheres Node User's Guide, which details the datasets stored on the Britton Lee, the structure of the query and data analysis system, and examples of the exact menu screens encountered. Also discussed were experience with the system, review of the system performance, and a strategy to produce queries and performance data retrievals of mutual interest. The goals were defined as examining correlations between cloud occurrence, water vapor abundance, and surface properties.

  13. Presentation Skills Workshops for Nurses.

    ERIC Educational Resources Information Center

    Kinn, S.; Kenyon, M.

    2002-01-01

    Workshops were held to prepare nurses (n=87) to present results of professional activities. One year after the course, 20 had made oral and 30 written presentations. The workshops increased their confidence and were considered practical, informal, and nonthreatening. (Contains 31 references.) (SK)

  14. 1973 Assessment Workshops: Final Report.

    ERIC Educational Resources Information Center

    Womer, Frank B.; Lehmann, Irvin J.

    Three 3-day assessment workshops were held in Boulder, Colorado from June 19-29, for personnel in the assessment field from state departments of education. Seventy-six participants from 35 states, Puerto Rico, the Virgin Islands and the District of Columbia attended. Two of the three workshops concentrated on National Assessment as one model for…

  15. A Person Centered Communication Workshop

    ERIC Educational Resources Information Center

    Boyd, John D.

    1977-01-01

    A person centered communication workshop was developed to help aspiring facilitators achieve a set of listening and responding skills with which to initiate and/or sustain facilitative interactions. The workshop has been helpful to teachers, teacher aides, counselors, speech-audiology therapists, and pupil personnel workers. (LBH)

  16. Dreissenid mussel research priorities workshop

    USGS Publications Warehouse

    Sytsma, Mark; Phillips, Stephen; Counihan, Timothy D.

    2016-01-01

    On November 4-5, 2015, a Dreissenid Mussel Research Priorities Workshop funded by the Great Northern Landscape Conservation Cooperative occurred at Portland State University. The purpose of the workshop was to update research priorities in the 2010 Quagga-Zebra Mussel Action Plan in light of the westward expansion of mussels in the United States and Canada.

  17. Burnout Workshops for Alcoholism Counselors.

    ERIC Educational Resources Information Center

    Sarata, B. P. V.

    1983-01-01

    Presents a general model for burnout workshops for alcoholism counselors, designed to involve counselors in a sequence of activities for coping adaptively. Data concerning the level and symptoms of burnout among counselors are provided. Suggestions for planning and leading a workshop are discussed. (JAC)

  18. Prescriptive Teaching Workshop Resource Manual.

    ERIC Educational Resources Information Center

    Bennett, Mildred E.; And Others

    The resource manual describes procedures for replication of a 1 year Prescriptive Teaching Workshop project, a Title III educational program designed to maintain the learning disabled elementary school child in the regular classroom with additional special workshop help in order to raise his academic achievement. Evaluation of the student is by a…

  19. Marketing Cooperative Education. A Workshop.

    ERIC Educational Resources Information Center

    Mosser, John W.; Rea, Peter J.

    This document is a guide for a workshop on marketing college cooperative education programs. The guide takes the reader/workshop participant through the marketing process, from defining needs and resources to planning a marketing campaign, implementing it, and evaluating its success. Samples and sources also are provided. Topics covered in the…

  20. Hydrogen Technology Education Workshop Proceedings

    SciTech Connect

    2002-12-01

    This document outlines activities for educating key target audiences, as suggested by workshop participants. Held December 4-5, 2002, the Hydrogen Technology Education Workshop kicked off a new education effort coordinated by the Hydrogen, Fuel Cells, & Infrastructure Technologies Program of the Office of Energy Efficiency and Renewable Energy.

  1. Manual for ERIC Awareness Workshop.

    ERIC Educational Resources Information Center

    Strohmenger, C. Todd; Lanham, Berma A.

    This manual, designed to be used with a video tape, provides information for conducting a workshop to familiarize educators with the Educational Resources Information Center (ERIC). Objectives of the workshop include: (1) to develop an understanding of the contents and structure of the ERIC database; (2) to develop an understanding of ERIC as a…

  2. Pre-Industrial Training Workshop.

    ERIC Educational Resources Information Center

    Amarillo Coll., TX.

    Participant materials are provided from a workshop to acquaint women with nontraditional careers in the skilled trades and to help them become more knowledgeable about their options in making informed career decisions. The agendas for five day-long sessions outline the scope of the workshop that emphasizes basic math skills, hands-on experiences…

  3. A Portable Computer Security Workshop

    ERIC Educational Resources Information Center

    Wagner, Paul J.; Phillips, Andrew T.

    2006-01-01

    We have developed a computer security workshop designed to instruct post-secondary instructors who want to start a course or laboratory exercise sequence in computer security. This workshop has also been used to provide computer security education to IT professionals and students. It is effective in communicating basic computer security principles…

  4. Report of the workshop on Aviation Safety/Automation Program

    NASA Technical Reports Server (NTRS)

    Morello, Samuel A. (Editor)

    1990-01-01

    As part of NASA's responsibility to encourage and facilitate active exchange of information and ideas among members of the aviation community, an Aviation Safety/Automation workshop was organized and sponsored by the Flight Management Division of NASA Langley Research Center. The one-day workshop was held on October 10, 1989, at the Sheraton Beach Inn and Conference Center in Virginia Beach, Virginia. Participants were invited from industry, government, and universities to discuss critical questions and issues concerning the rapid introduction and utilization of advanced computer-based technology into the flight deck and air traffic controller workstation environments. The workshop was attended by approximately 30 discipline experts, automation and human factors researchers, and research and development managers. The goal of the workshop was to address major issues identified by the NASA Aviation Safety/Automation Program. Here, the results of the workshop are documented. The ideas, thoughts, and concepts were developed by the workshop participants. The findings, however, have been synthesized into a final report primarily by the NASA researchers.

  5. Summaries of the Sixth Annual JPL Airborne Earth Science Workshop. Volume 1; AVIRIS Workshop

    NASA Technical Reports Server (NTRS)

    Green, Robert O. (Editor)

    1996-01-01

    This publication contains the summaries for the Sixth Annual JPL Airborne Earth Science Workshop, held in Pasadena, California, on March 4-8, 1996. The main workshop is divided into two smaller workshops as follows: (1) The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on March 4-6. The summaries for this workshop appear in Volume 1; (2) The Airborne Synthetic Aperture Radar (AIRSAR) workshop, on March 6-8. The summaries for this workshop appear in Volume 2.

  6. INTERCONNECTIONS BETWEEN HUMAN HEALTH AND ECOLOGICAL INTEGRITY

    EPA Science Inventory

    Interconnections between Human Health and Ecological Integrity emanates from a June 2000 Pellston Workshop in Snowbird, Utah, USA. Jointly sponsored by the Society of Environmental Toxicology and Chemistry (SETAC) and the Society of Toxicology (SOT), the workshop was motivated by...

  7. NASA Discovery Program Workshop

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The purpose of the workshop was to review concepts for Discover-class missions that would follow the first two missions (MESUR-Pathfinder and NEAR) of this new program. The concepts had been generated by scientists involved in NASA's Solar System Exploration Program to carry out scientifically important investigations within strict guidelines -- $150 million cap on development cost and 3 year cap on development schedule. Like the Astrophysics Small Explorers (SMEX), such 'faster and cheaper' missions could provide vitality to solar system exploration research by returning high quality data more frequently and regularly and by involving many more young researchers than normally participate directly in larger missions. An announcement of opportunity (AO) to propose a Discovery mission to NASA is expected to be released in about two years time. One purpose of the workshop was to assist Code SL in deciding how to allocate its advanced programs resources. A second, complimentary purpose was to provide the concept proposers with feedback to allow them to better prepare for the AO.

  8. Microgravity Combustion Diagnostics Workshop

    NASA Technical Reports Server (NTRS)

    Santoro, Gilbert J. (Editor); Greenberg, Paul S. (Editor); Piltch, Nancy D. (Editor)

    1988-01-01

    Through the Microgravity Science and Applications Division (MSAD) of the Office of Space Science and Applications (OSSA) at NASA Headquarters, a program entitled, Advanced Technology Development (ATD) was promulgated with the objective of providing advanced technologies that will enable the development of future microgravity science and applications experimental flight hardware. Among the ATD projects one, Microgravity Combustion Diagnostics (MCD), has the objective of developing advanced diagnostic techniques and technologies to provide nonperturbing measurements of combustion characteristics and parameters that will enhance the scientific integrity and quality of microgravity combustion experiments. As part of the approach to this project, a workshop was held on July 28 and 29, 1987, at the NASA Lewis Research Center. A small group of laser combustion diagnosticians met with a group of microgravity combustion experimenters to discuss the science requirements, the state-of-the-art of laser diagnostic technology, and plan the direction for near-, intermediate-, and long-term programs. This publication describes the proceedings of that workshop.

  9. Avian polyomavirus infection of a fledgling budgerigar (Melopsittacus undulatus) and differential diagnoses of viral inclusions in psittacine birds--case report and mini-review.

    PubMed

    Herder, Vanessa; König, Anett; Seehusen, Frauke; Wohlsein, Peter

    2011-01-01

    A two-week-old budgerigar (Melopsittacus undulatus) of an outdoor aviary died suddenly and was submitted for determination the cause of illness and death. Macroscopically, the sparsely feathered animal was in a poor body condition. Histopathological examination revealed in various mesenchymal and epithelial tissues, numerous up to 15 microm in diameter large intranuclear, amphophilic to basophilic inclusion bodies with a clearing of the centre. Additionally, a feather dysplasia and retention hyperkeratosis of feather follicles was found. Ultrastructurally, viral particles of approximately 35 nm in diameter were detected in the feather follicle epithelium. A PCR for Avian Polyomavirus on fresh skin samples was negative whereas on formalin-fixed kidney samples with a high amount of viral inclusion bodies yielded a positive result. In addition, viral inclusion body diseases, like Avian Poxvirus, Psittacine Beak and Feather disease virus, Avian Adenovirus, Psittacine Herpesvirus and papillomavirus of psittacines are summarized and compared in the present article. PMID:22059291

  10. Peptide Immunization Elicits Polyomavirus-Specific MHC Class Ib-Restricted CD8 T Cells in MHC Class Ia Allogeneic Mice

    PubMed Central

    Hofstetter, Amelia R.; Evavold, Brian D.

    2013-01-01

    Abstract Unlike the polymorphic MHC class Ia molecules, MHC class Ib molecules are oligomorphic or nonpolymorphic. We recently discovered a protective CD8 T cell response to mouse polyomavirus (MPyV) in H-2b haplotype mice that is restricted by H2-Q9, a member of the Qa-2 MHC class Ib family. Here, we demonstrate that immunization with a peptide corresponding to a virus capsid-derived peptide presented by Q9 also elicits MHC class Ib-restricted MPyV-specific CD8 T cells in mice of H-2s and H-2g7 strains. These findings support the concept that immunization with a single MHC class Ib-restricted peptide can expand CD8 T cells in MHC class Ia allogeneic hosts. PMID:23374150

  11. 1991 NASA Life Support Systems Analysis workshop

    NASA Technical Reports Server (NTRS)

    Evanich, Peggy L.; Crabb, Thomas M.; Gartrell, Charles F.

    1992-01-01

    The 1991 Life Support Systems Analysis Workshop was sponsored by NASA Headquarters' Office of Aeronautics and Space Technology (OAST) to foster communication among NASA, industrial, and academic specialists, and to integrate their inputs and disseminate information to them. The overall objective of systems analysis within the Life Support Technology Program of OAST is to identify, guide the development of, and verify designs which will increase the performance of the life support systems on component, subsystem, and system levels for future human space missions. The specific goals of this workshop were to report on the status of systems analysis capabilities, to integrate the chemical processing industry technologies, and to integrate recommendations for future technology developments related to systems analysis for life support systems. The workshop included technical presentations, discussions, and interactive planning, with time allocated for discussion of both technology status and time-phased technology development recommendations. Key personnel from NASA, industry, and academia delivered inputs and presentations on the status and priorities of current and future systems analysis methods and requirements.

  12. Sheltered Workshop Study. A Nationwide Report on Sheltered Workshops and Their Employment of Handicapped Individuals. Volume I. Workshop Survey.

    ERIC Educational Resources Information Center

    Employment and Training Administration (DOL), Washington, DC.

    Presented are results from a survey of 2,530 sheltered workshop programs serving handicapped persons. Initial sections review the historical development of workshops, federal regulations affecting workshops, and previous related studies. Data are provided on the following topics: characteristics of workshops and clients (including a table on…

  13. Disease screening of three breeding populations of adult exhibition budgerigars (Melopsittacus undulatus) in New Zealand reveals a high prevalence of a novel polyomavirus and avian malaria infection.

    PubMed

    Baron, Hamish R; Howe, Laryssa; Varsani, Arvind; Doneley, Robert J T

    2014-03-01

    Disease surveillance is vital to the management of New Zealand's endemic and threatened avian species. Three infectious agents that are potential threats to New Zealand's endemic birds include avian polyomavirus (APV), beak and feather disease virus (BFDV), and avian malaria. All three agents have been reported in New Zealand; however, possible reservoir populations have not been identified. In this communication, we report the first study of APV, BFDV, and avian malaria in introduced adult exhibition budgerigars (Melopsittacus undulatus) in New Zealand. Blood samples were collected from 90 living adult budgerigars from three breeding locations in the North Island of New Zealand. An overall APV prevalence of 22% was determined using a broad-spectrum nested PCR that amplified the major capsid protein VP1 gene of polyomavirus. Phylogenetic analysis of the VP1 gene revealed a unique isolate of APV, which had a sequence divergence of 32% to previously reported budgerigar fledgling disease strains and 33% to the recently reported New Zealand finch isolate. All of the budgerigars sampled were found to be PCR negative for BFDV, and an overall prevalence of 30% was detected by PCR for avian malaria. Sequencing revealed the presence of ubiquitous malarial strains and also the potentially destructive Plasmodium relictum strain. The results of this study suggest that both APV and avian malaria are present in New Zealand adult budgerigars, and our study highlights the need for further studies to determine whether these pathogens in captive bird populations may be a threat or spill over into New Zealand's endemic and threatened avifauna and whether prevention and control methods need to be implemented. PMID:24758122

  14. Detection of Merkel cell polyomavirus in formalin-fixed, paraffin-embedded tissue of Merkel cell carcinoma and correlation with prognosis.

    PubMed

    Andea, Aleodor A; Patel, Raj; Ponnazhagan, Selvarangan; Isayeva, Tatyana; Kumar, Sanjay; Siegal, Gene P

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare, but highly aggressive primary cutaneous malignancy, showing neuroendocrine differentiation. In 2008, a novel member of the polyomavirus family, named Merkel cell polyomavirus (MCPyV) was identified in the genome of MCC tumors raising the possibility of an involvement in its pathogenesis. Due to the rarity of this tumor and current pathology practices, the most readily available tissue is archival formalin-fixed, paraffin-embedded (FFPE) material. In this study, we evaluated the presence of MCPyV in FFPE tissue and correlated its presence with tumor progression. Representative FFPE specimens from 18 tumors belonging to 14 patients with a diagnosis of MCC spanning the period from 2003 to 2008 were retrieved. Following DNA extraction, we performed PCR amplification and sequencing with four different MCPyV-specific primer pairs mapping within the T antigen and VP1 region. Overall, we detected MCPyV amplicons in 8/18 (44.4%) analyzed tumors from 7/14 (50%) cases. Two-year survival rate and median survival for the MCPyV-positive MCCs were 48% and 22.5 months, respectively and for the negative ones 69% and 51.3 months, respectively; however, the difference did not reach statistical significance (p=0.8). There was no significant correlation between the presence of the virus and the stage at presentation; however, tumors in the head and neck area had a lower frequency of viral positivity compared to those arising in the extremities suggesting a MCPyV-independent oncogenetic pathway perhaps, dependent on UV exposure, in a subset of these cases.

  15. Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells*

    PubMed Central

    Dugan, Aisling S.; Maginnis, Melissa S.; Jordan, Joslynn A.; Gasparovic, Megan L.; Manley, Kate; Page, Rebecca; Williams, Geoffrey; Porter, Edith; O'Hara, Bethany A.; Atwood, Walter J.

    2008-01-01

    BK virus (BKV) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. The function of the innate immune system in BKV infection and pathology has not been investigated. Here we examine the role of antimicrobial defensins in BKV infection of Vero cells. Our data show that α-defensin human neutrophil protein 1 (HNP1) and human α-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. HD5 treatment of BKV reduced viral attachment to cells, whereas cellular treatment with HD5 did not. Colocalization studies indicated that HD5 interacts directly with BKV. Ultrastructural analysis revealed HD5-induced aggregation of virions. HD5 also inhibited infection of cells by other related polyomaviruses. This is the first study to demonstrate polyomavirus sensitivity to defensins. We also show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventing normal virus binding to the cell surface and uptake into cells. PMID:18782756

  16. Summaries of the 4th Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1993-01-01

    This is volume 2 of a three volume set of publications that contain the summaries for the Fourth Annual JPL Airborne Geoscience Workshop, held in Washington, D.C. on October 25-29, 1993. The main workshop is divided into three smaller workshops as follows: The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on October 25-26. The summaries for this workshop appear in Volume 1. The Thermal Infrared Multispectral Scanner (TIMS) workshop, on October 27. The summaries for this workshop appear in Volume 2. The Airborne Synthetic Aperture Radar (AIRSAR) workshop, on October 28-29. The summaries for this workshop appear in Volume 3.

  17. Summaries of the Third Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1992-01-01

    This publication contains the preliminary agenda and summaries for the Third Annual JPL Airborne Geoscience Workshop, held at the Jet Propulsion Laboratory, Pasadena, California, on 1-5 June 1992. This main workshop is divided into three smaller workshops as follows: (1) the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on June 1 and 2; the summaries for this workshop appear in Volume 1; (2) the Thermal Infrared Multispectral Scanner (TIMS) workshop, on June 3; the summaries for this workshop appear in Volume 2; and (3) the Airborne Synthetic Aperture Radar (AIRSAR) workshop, on June 4 and 5; the summaries for this workshop appear in Volume 3.

  18. Summaries of the Fifth Annual JPL Airborne Earth Science Workshop. Volume 1: AVIRIS Workshop

    NASA Technical Reports Server (NTRS)

    Green, Robert O. (Editor)

    1995-01-01

    This publication is the first of three containing summaries for the Fifth Annual JPL Airborne Earth Science Workshop, held in Pasadena, California, on January 23-26, 1995. The main workshop is divided into three smaller workshops as follows: (1) The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on January 23-24. The summaries for this workshop appear in this volume; (2) The Airborne Synthetic Aperture Radar (AIRSAR) workshop, on January 25-26. The summaries for this workshop appear in Volume 3; and (3) The Thermal Infrared Multispectral Scanner (TIMS) workshop, on January 26. The summaries for this workshop appear in Volume 2.

  19. Summaries of the Fifth Annual JPL Airborne Earth Science Workshop. Volume 2: TIMS Workshop

    NASA Technical Reports Server (NTRS)

    Realmuto, Vincent J. (Editor)

    1995-01-01

    This publication is the second volume of the summaries for the Fifth Annual JPL Airborne Earth Science Workshop, held in Pasadena, California, on January 23-26, 1995. The main workshop is divided into three smaller workshops as follows: (1) The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop on January 23-24. The summaries for this workshop appear in Volume 1; (2) The Airborne Synthetic Aperture Radar (AIRSAR) workshop on January 25-26. The summaries for this workshop appear in volume 3; and (3) The Thermal Infrared Multispectral Scanner (TIMS) workshop on January 26. The summaries for this workshop appear in this volume.

  20. Summaries of the 4th Annual JPL Airborne Geoscience Workshop. Volume 1: AVIRIS Workshop

    NASA Technical Reports Server (NTRS)

    Green, Robert O. (Editor)

    1993-01-01

    This publication contains the summaries for the Fourth Annual JPL Airborne Geoscience Workshop, held in Washington, D. C. October 25-29, 1993 The main workshop is divided into three smaller workshops as follows: The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, October 25-26 (the summaries for this workshop appear in this volume, Volume 1); The Thermal Infrared Multispectral Scanner (TMIS) workshop, on October 27 (the summaries for this workshop appear in Volume 2); and The Airborne Synthetic Aperture Radar (AIRSAR) workshop, October 28-29 (the summaries for this workshop appear in Volume 3).