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Sample records for ectodomain shedding implications

  1. Secretome analysis to elucidate metalloprotease-dependent ectodomain shedding of glycoproteins during neuronal differentiation.

    Science.gov (United States)

    Tsumagari, Kazuya; Shirakabe, Kyoko; Ogura, Mayu; Sato, Fuminori; Ishihama, Yasushi; Sehara-Fujisawa, Atsuko

    2017-02-01

    Many membrane proteins are subjected to limited proteolyses at their juxtamembrane regions, processes referred to as ectodomain shedding. Shedding ectodomains of membrane-bound ligands results in activation of downstream signaling pathways, whereas shedding those of cell adhesion molecules causes loss of cell-cell contacts. Secreted proteomics (secretomics) using high-resolution mass spectrometry would be strong tools for both comprehensive identification and quantitative measurement of membrane proteins that undergo ectodomain shedding. In this study, to elucidate the ectodomain shedding events that occur during neuronal differentiation, we establish a strategy for quantitative secretomics of glycoproteins released from differentiating neuroblastoma cells into culture medium with or without GM6001, a broad-spectrum metalloprotease inhibitor. Considering that most of transmembrane and secreted proteins are N-glycosylated, we include a process of N-glycosylated peptides enrichment as well as isotope tagging in our secretomics workflow. Our results show that differentiating N1E-115 neurons secrete numerous glycosylated polypeptides in metalloprotease-dependent manners. They are derived from cell adhesion molecules such as NCAM1, CADM1, L1CAM, various transporters and receptor proteins. These results show the landscape of ectodomain shedding and other secretory events in differentiating neurons and/or during axon elongation, which should help elucidate the mechanism of neurogenesis and the pathogenesis of neurological disorders. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  2. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK.

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    Steve Pedrini

    2005-01-01

    Full Text Available Statins are widely used cholesterol-lowering drugs that act by inhibiting HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent evidence suggests that statin use may be associated with a decreased risk for Alzheimer disease, although the mechanisms underlying this apparent risk reduction are poorly understood. One popular hypothesis for statin action is related to the drugs' ability to activate alpha-secretase-type shedding of the alpha-secretase-cleaved soluble Alzheimer amyloid precursor protein ectodomain (sAPP(alpha. Statins also inhibit the isoprenoid pathway, thereby modulating the activities of the Rho family of small GTPases-Rho A, B, and C-as well as the activities of Rac and cdc42. Rho proteins, in turn, exert many of their effects via Rho-associated protein kinases (ROCKs. Several cell-surface molecules are substrates for activated alpha-secretase-type ectodomain shedding, and regulation of shedding typically occurs via activation of protein kinase C or extracellular-signal-regulated protein kinases, or via inactivation of protein phosphatase 1 or 2A. However, the possibility that these enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved.We found that both atorvastatin and simvastatin stimulated sAPP(alpha shedding from a neuroblastoma cell line via a subcellular mechanism apparently located upstream of endocytosis. A farnesyl transferase inhibitor also increased sAPP(alpha shedding, as did a dominant negative form of ROCK1. Most conclusively, a constitutively active ROCK1 molecule inhibited statin-stimulated sAPP(alpha shedding.Together, these data suggest that statins exert their effects on shedding of sAPP(alpha from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1.

  3. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

    OpenAIRE

    Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

    2005-01-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test ...

  4. The effect of structural motifs on the ectodomain shedding of human angiotensin-converting enzyme.

    Science.gov (United States)

    Conrad, Nailah; Schwager, Sylva L U; Carmona, Adriana K; Sturrock, Edward D

    2016-12-02

    Somatic angiotensin converting enzyme (sACE) is comprised of two homologous domains (N and C domains), whereas the smaller germinal isoform (tACE) is identical to the C domain. Both isozymes share an identical stalk, transmembrane and cytoplasmic domain, and undergo ectodomain shedding by an as yet unknown protease. Here we present evidence for the role of regions distal and proximal to the cleavage site in human ACE shedding. First, because of intrinsic differences between the N and C domains, discrete secondary structures (α-helix 7 and 8) on the surface of tACE were replaced with their N domain counterparts. Surprisingly, neither α-helix 7 nor α-helix 8 proved to be an absolute requirement for shedding. In the proximal ectodomain of tACE residues H 610 -L 614 were mutated to alanines and this resulted in a decrease in ACE shedding. An N-terminal extension of this mutation caused a reduction in cellular ACE activity. More importantly, it affected the processing of the protein to the membrane, resulting in expression of an underglycosylated form of ACE. When E 608 -H 614 was mutated to the homologous region of the N domain, processing was normal and shedding only moderately decreased suggesting that this region is more crucial for the processing of ACE than it is for regulating shedding. Finally, to determine whether glycosylation of the asparagine proximal to the Pro1199-Leu polymorphism in sACE affected shedding, the equivalent P 623 L mutation in tACE was investigated. The P 623 L tACE mutant showed an increase in shedding and MALDI MS analysis of a tryptic digest indicated that N 620 WT was glycosylated. The absence of an N-linked glycan at N 620 , resulted in an even greater increase in shedding. Thus, the conformational flexibility that the leucine confers to the stalk, is increased by the lack of glycosylation reducing access of the sheddase to the cleavage site. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding

    Directory of Open Access Journals (Sweden)

    Lovestone Simon

    2007-12-01

    Full Text Available Abstract Background Shedding of the Alzheimer amyloid precursor protein (APP ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s. However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Results Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner et al (2004, phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα. Conclusion Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

  6. Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding.

    Science.gov (United States)

    Ikin, Annat F; Causevic, Mirsada; Pedrini, Steve; Benson, Lyndsey S; Buxbaum, Joseph D; Suzuki, Toshiharu; Lovestone, Simon; Higashiyama, Shigeki; Mustelin, Tomas; Burgoyne, Robert D; Gandy, Sam

    2007-12-09

    Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Rossner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPalpha. Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

  7. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

    Science.gov (United States)

    Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

    2005-08-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

  8. Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis.

    Science.gov (United States)

    Mishra, Hemant K; Ma, Jing; Walcheck, Bruce

    2017-01-01

    Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

  9. ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells.

    Science.gov (United States)

    Duan, Xiaohui; Mao, Xianhai; Sun, Weijia

    2013-03-01

    The aim of this study was to investigate the role of ADAM15 in MHC class I polypeptide-related sequence B (MICB) protein ectodomain shedding and observe whether or not gemcitabine affects MICB shedding from PANC-1 cells. In this study, immunohistochemistry of MICB and ADAM15 were performed on tumor samples obtained from 93 patients with pancreatic ductal adenocarcinoma (PDAC). The expression of MICB and ADAM15 in the PDAC tissues was significantly higher compared with that in the normal tissues of the pancreas. Statistical analysis showed a significant correlation between the expression of MICB and certain classic clinicopathological characteristics (i.e., histological grade and TNM stage). ADAM15 expression was found to correlate with lymph node metastasis and TNM stage. The Spearman's rank test suggested that the expression of MICB was inversely correlated with that of ADAM15 in PDAC tissues. Knockdown of ADAM15 in PANC-1 cells clearly upregulated MICB expression on the cellular surface and downregulated soluble MICB (sMICB) levels in the culture supernatants. A non-toxic dose of 0.5 µmol/l gemcitabine suppresses ADAM15 expression leading, at the same time, to an increase in MICB expression and a decrease in sMICB production in PANC-1 cells. The mRNA levels of MICB did not change following PANC-1 exposure to gemcitabine. Further study suggests that the suppressive effect of gemcitabine on MICB shedding in PANC-1 cells is mediated by ADAM15 downregulation. In conclusion, the results of the present study support the hypothesis that ADAM15 is involved in MICB shedding of PANC-1 cells and that gemcitabine inhibits MICB ectodomain shedding through the suppression of ADAM15.

  10. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    International Nuclear Information System (INIS)

    Roche, Julien; Louis, John M.; Aniana, Annie; Ghirlando, Rodolfo; Bax, Ad

    2015-01-01

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion

  11. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  12. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo

    2012-01-01

    ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell-surface ......ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell...

  13. Structure of the parainfluenza virus 5 (PIV5 hemagglutinin-neuraminidase (HN ectodomain.

    Directory of Open Access Journals (Sweden)

    Brett D Welch

    Full Text Available Paramyxoviruses cause a wide variety of human and animal diseases. They infect host cells using the coordinated action of two surface glycoproteins, the receptor binding protein (HN, H, or G and the fusion protein (F. HN binds sialic acid on host cells (hemagglutinin activity and hydrolyzes these receptors during viral egress (neuraminidase activity, NA. Additionally, receptor binding is thought to induce a conformational change in HN that subsequently triggers major refolding in homotypic F, resulting in fusion of virus and target cell membranes. HN is an oligomeric type II transmembrane protein with a short cytoplasmic domain and a large ectodomain comprising a long helical stalk and large globular head domain containing the enzymatic functions (NA domain. Extensive biochemical characterization has revealed that HN-stalk residues determine F specificity and activation. However, the F/HN interaction and the mechanisms whereby receptor binding regulates F activation are poorly defined. Recently, a structure of Newcastle disease virus (NDV HN ectodomain revealed the heads (NA domains in a "4-heads-down" conformation whereby two of the heads form a symmetrical interaction with two sides of the stalk. The interface includes stalk residues implicated in triggering F, and the heads sterically shield these residues from interaction with F (at least on two sides. Here we report the x-ray crystal structure of parainfluenza virus 5 (PIV5 HN ectodomain in a "2-heads-up/2-heads-down" conformation where two heads (covalent dimers are in the "down position," forming a similar interface as observed in the NDV HN ectodomain structure, and two heads are in an "up position." The structure supports a model in which the heads of HN transition from down to up upon receptor binding thereby releasing steric constraints and facilitating the interaction between critical HN-stalk residues and F.

  14. Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons.

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    Sanz, Ricardo L; Ferraro, Gino B; Girouard, Marie-Pier; Fournier, Alyson E

    2017-08-11

    IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.

  15. Hepatocyte growth factor inhibitor-2 prevents shedding of matritpase

    DEFF Research Database (Denmark)

    Larsen, Brian R; Steffensen, Simon D; Nielsen, Nis V L

    2013-01-01

    Hepatocyte growth factor activator inhibitor-2 (HAI-2) is an inhibitor of many proteases in vitro, including the membrane-bound serine protease, matriptase. Studies of knock-out mice have shown that HAI-2 is essential for placental development only in mice expressing matriptase, suggesting that HAI......-2 is important for regulation of matriptase. Previous studies have shown that recombinant expression of matriptase was unsuccessful unless co-expressed with another HAI, HAI-1. In the present study we show that when human matriptase is recombinantly expressed alone in the canine cell line MDCK......, then human matriptase mRNA can be detected and the human matriptase ectodomain is shed to the media, suggesting that matriptase expressed alone is rapidly transported through the secretory pathway and shed. Whereas matriptase expressed together with HAI-1 or HAI-2 accumulates on the plasma membrane where...

  16. Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

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    Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

    2015-03-17

    Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, Pbladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

  17. Structural model and trans-interaction of the entire ectodomain of the olfactory cell adhesion molecule

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Kristensen, Ole; Rasmussen, Kim K

    2011-01-01

    of six recombinant proteins corresponding to different regions of the ectodomain. The model is the longest experimentally based composite structural model of an entire IgCAM ectodomain. It displays an essentially linear arrangement of IgI-V, followed by bends between IgV and Fn3I and between Fn3I and Fn3...

  18. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  19. The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

    International Nuclear Information System (INIS)

    Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel; Igonet, Sebastien; Oldstone, Michael B.A.; Kunz, Stefan

    2013-01-01

    Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

  20. The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

    Energy Technology Data Exchange (ETDEWEB)

    Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland); Igonet, Sebastien; Oldstone, Michael B.A. [Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 (United States); Kunz, Stefan, E-mail: Stefan.Kunz@chuv.ch [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland)

    2013-02-05

    Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

  1. Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

    Science.gov (United States)

    Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

    2015-01-01

    No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by

  2. Deletion of thyrotropin receptor residue Asp403 in a hyperfunctioning thyroid nodule provides insight into the role of the ectodomain in ligand-induced receptor activation.

    Science.gov (United States)

    Nishihara, E; Chen, C-R; Mizutori-Sasai, Y; Ito, M; Kubota, S; Amino, N; Miyauchi, A; Rapoport, B

    2012-01-01

    Somatic mutations of the TSH receptor (TSHR) gene are the main cause of autonomously functioning thyroid nodules. Except for mutations in ectodomain residue S281, all of the numerous reported activating mutations are in the TSHR membrane-spanning region. Here, we describe a patient with a toxic adenoma with a novel heterozygous somatic mutation caused by deletion of ectodomain residue Asp403 (Del-D403). Subsequent in vitro functional studies of the Del-D403 TSHR mutation demonstrated greatly increased ligand-independent constitutive activity, 8-fold above that of the wild-type TSHR. TSH stimulation had little further effect, indicating that the mutation produced near maximal activation of the receptor. In summary, we report only the second TSHR ectodomain activating mutation (and the first ectodomain deletion mutation) responsible for development of a thyroid toxic adenoma. Because Del-D403 causes near maximal activation, our finding provides novel insight into TSHR structure and function; residue D403 is more likely to be involved in the ligand-mediated activating pathway than in the ectodomain inverse agonist property.

  3. Characterization of the ectodomain of the envelope protein of dengue virus type 4: expression, membrane association, secretion and particle formation in the absence of precursor membrane protein.

    Directory of Open Access Journals (Sweden)

    Szu-Chia Hsieh

    Full Text Available The envelope (E of dengue virus (DENV is the major target of neutralizing antibodies and vaccine development. After biosynthesis E protein forms a heterodimer with precursor membrane (prM protein. Recent reports of infection enhancement by anti-prM monoclonal antibodies (mAbs suggest anti-prM responses could be potentially harmful. Previously, we studied a series of C-terminal truncation constructs expressing DENV type 4 prM/E or E proteins and found the ectodomain of E protein alone could be recognized by all 12 mAbs tested, suggesting E protein ectodomain as a potential subunit immunogen without inducing anti-prM response. The characteristics of DENV E protein ectodomain in the absence of prM protein remains largely unknown.In this study, we investigated the expression, membrane association, glycosylation pattern, secretion and particle formation of E protein ectodomain of DENV4 in the presence or absence of prM protein. E protein ectodomain associated with membrane in or beyond trans-Golgi and contained primarily complex glycans, whereas full-length E protein associated with ER membrane and contained high mannose glycans. In the absence of prM protein, E protein ectodomain can secrete as well as form particles of approximately 49 nm in diameter, as revealed by sucrose gradient ultracentrifugation with or without detergent and electron microscopy. Mutational analysis revealed that the secretion of E protein ectodomain was affected by N-linked glycosylation and could be restored by treatment with ammonia chloride.Considering the enhancement of DENV infectivity by anti-prM antibodies, our findings provide new insights into the expression and secretion of E protein ectodomain in the absence of prM protein and contribute to future subunit vaccine design.

  4. The rice XA21 ectodomain fused to the Arabidopsis EFR cytoplasmic domain confers resistance to Xanthomonas oryzae pv. oryzae.

    Science.gov (United States)

    Thomas, Nicholas C; Oksenberg, Nir; Liu, Furong; Caddell, Daniel; Nalyvayko, Alina; Nguyen, Yen; Schwessinger, Benjamin; Ronald, Pamela C

    2018-01-01

    Rice ( Oryza sativa ) plants expressing the XA21 cell-surface receptor kinase are resistant to Xanthomonas oryzae pv. oryzae (Xoo) infection. We previously demonstrated that expressing a chimeric protein containing the ELONGATION FACTOR Tu RECEPTOR (EFR) ectodomain and the XA21 endodomain (EFR:XA21) in rice does not confer robust resistance to Xoo . To test if the XA21 ectodomain is required for Xoo resistance, we produced transgenic rice lines expressing a chimeric protein consisting of the XA21 ectodomain and EFR endodomain (XA21:EFR) and inoculated these lines with Xoo . We also tested if the XA21:EFR rice plants respond to a synthetic sulfated 21 amino acid derivative (RaxX21-sY) of the activator of XA21-mediated immunity, RaxX. We found that five independently transformed XA21:EFR rice lines displayed resistance to Xoo as measured by lesion length analysis, and showed that five lines share characteristic markers of the XA21 defense response (generation of reactive oxygen species and defense response gene expression) after treatment with RaxX21-sY. Our results indicate that expression of the XA21:EFR chimeric receptor in rice confers resistance to Xoo . These results suggest that the endodomain of the EFR and XA21 immune receptors are interchangeable and the XA21 ectodomain is the key determinant conferring robust resistance to Xoo .

  5. Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

    Science.gov (United States)

    Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

    2012-01-01

    Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

  6. Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function.

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    Jianjun Sun

    Full Text Available BACKGROUND: Cell-surface receptors play essential roles in anthrax toxin action by providing the toxin with a high-affinity anchor and self-assembly site on the plasma membrane, mediating the toxin entry into cells through endocytosis, and shifting the pH threshold for prepore-to-pore conversion of anthrax toxin protective antigen (PA to a more acidic pH, thereby inhibiting premature pore formation. Each of the two known anthrax toxin receptors, ANTXR1 and ANTXR2, has an ectodomain comprised of an N-terminal von Willebrand factor A domain (VWA, which binds PA, and an uncharacterized immunoglobulin-like domain (Ig that connects VWA to the membrane-spanning domain. Potential roles of the receptor Ig domain in anthrax toxin action have not been investigated heretofore. METHODOLOGY/PRINCIPAL FINDINGS: We expressed and purified the ANTXR2 ectodomain (R2-VWA-Ig in E. coli and showed that it contains three disulfide bonds: one in R2-VWA and two in R2-Ig. Reduction of the ectodomain inhibited functioning of the pore, as measured by K(+ release from liposomes or Chinese hamster ovary cells or by PA-mediated translocation of a model substrate across the plasma membrane. However, reduction did not affect binding of the ectodomain to PA or the transition of ectodomain-bound PA prepore to the pore conformation. The inhibitory effect depended specifically on reduction of the disulfides within R2-Ig. CONCLUSIONS/SIGNIFICANCE: We conclude that disulfide integrity within R2-Ig is essential for proper functioning of receptor-bound PA pore. This finding provides a novel venue to investigate the mechanism of anthrax toxin action and suggests new strategies for inhibiting toxin action.

  7. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  8. Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

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    Tineke W H Meijer

    Full Text Available BACKGROUND AND PURPOSE: Carbonic anhydrase IX (CAIX plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl-ureidophenyl sulfamate (S4 on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding. METHODS: SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR. RESULTS: CAIX ectodomain shedding decreased after treatment with S4 (p<0.01. S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed. CONCLUSION: As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.

  9. Ectodomain of plasmodesmata-localized protein 5 in Arabidopsis: expression, purification, crystallization and crystallographic analysis.

    Science.gov (United States)

    Wang, Xiaocui; Zhu, Peiyan; Qu, Shanshan; Zhao, Jie; Singh, Prashant K; Wang, Wei

    2017-09-01

    Plasmodesmata-localized protein 5 (PDLP5) is a cysteine-rich receptor-like protein which is localized on the plasmodesmata of Arabidopsis thaliana. Overexpression of PDLP5 can reduce the permeability of the plasmodesmata and further affect the cell-to-cell movement of viruses and macromolecules in plants. The ectodomain of PDLP5 contains two DUF26 domains; however, the function of these domains is still unknown. Here, the ectodomain of PDLP5 from Arabidopsis was cloned and overexpressed using an insect expression system and was then purified and crystallized. X-ray diffraction data were collected to 1.90 Å resolution and were indexed in space group P1, with unit-cell parameters a = 41.9, b = 48.1, c = 62.2 Å, α = 97.3, β = 103.1, γ = 99.7°. Analysis of the crystal content indicated that there are two molecules in the asymmetric unit, with a Matthews coefficient of 2.51 Å 3  Da -1 and a solvent content of 50.97%.

  10. Expression, purification and crystallization of the ectodomain of the envelope glycoprotein E2 from Bovine viral diarrhoea virus

    International Nuclear Information System (INIS)

    Iourin, Oleg; Harlos, Karl; El Omari, Kamel; Lu, Weixian; Kadlec, Jan; Iqbal, Munir; Meier, Christoph; Palmer, Andrew; Jones, Ian; Thomas, Carole; Brownlie, Joe; Grimes, Jonathan M.; Stuart, David I.

    2012-01-01

    The cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the ectodomain of BVDV E2 are described. Bovine viral diarrhoea virus (BVDV) is an economically important animal pathogen which is closely related to Hepatitis C virus. Of the structural proteins, the envelope glycoprotein E2 of BVDV is the major antigen which induces neutralizing antibodies; thus, BVDV E2 is considered as an ideal target for use in subunit vaccines. Here, the expression, purification of wild-type and mutant forms of the ectodomain of BVDV E2 and subsequent crystallization and data collection of two crystal forms grown at low and neutral pH are reported. Native and multiple-wavelength anomalous dispersion (MAD) data sets have been collected and structure determination is in progress

  11. Counter and Complicit Masculine Discourse Among Men's Shed Members.

    Science.gov (United States)

    Mackenzie, Corey S; Roger, Kerstin; Robertson, Steve; Oliffe, John L; Nurmi, Mary Anne; Urquhart, James

    2017-07-01

    Men's Sheds is a growing international movement aimed at providing men with places and activities that facilitate social connectedness. Despite Men's Sheds' focus on males, little attention has been paid to masculinities within the specific context of these settings. The current study used a gender relations framework to explore the ways in which attendees discussed Men's Sheds, with particular attention to discussions that were complicit and counter to traditional, hegemonic views of masculinity, and diverse positions in between these binaries. The data consisted of transcripts and field notes from four focus groups comprising mostly older, White, retired male members of a Canadian shed ( N = 22). The analysis revealed three overall themes: (1) focus on work, (2) independence, and (3) need for male-focused spaces. These themes and associated subthemes suggest that shed members ascribe to dominant masculine values and ideals, but also support more fluid and flexible views of masculinity. Implications are discussed for how working with an array of masculinities within the Men's Sheds movement will be helpful with respect to their future growth in Canada and internationally.

  12. An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release

    International Nuclear Information System (INIS)

    Adamik, Barbara; Islam, Aminul; Rouhani, Farshid N.; Hawari, Feras I.; Zhang Jing; Levine, Stewart J.

    2008-01-01

    The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1β-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1β-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains

  13. Middle East respiratory syndrome coronavirus (MERS-CoV viral shedding in the respiratory tract: an observational analysis with infection control implications

    Directory of Open Access Journals (Sweden)

    Ziad A. Memish

    2014-12-01

    Conclusions: Contacts cleared MERS-CoV earlier than ill patients. This finding could be related to the types of sample as well as the types of patient studied. More ill patients with significant comorbidities shed the virus for a significantly longer time. The results of this study could have critical implications for infection control guidance and its application in healthcare facilities handling positive cases.

  14. A novel Arabidopsis CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) mutant with enhanced pathogen-induced cell death and altered receptor processing.

    Science.gov (United States)

    Petutschnig, Elena K; Stolze, Marnie; Lipka, Ulrike; Kopischke, Michaela; Horlacher, Juliane; Valerius, Oliver; Rozhon, Wilfried; Gust, Andrea A; Kemmerling, Birgit; Poppenberger, Brigitte; Braus, Gerhard H; Nürnberger, Thorsten; Lipka, Volker

    2014-12-01

    Plants detect pathogens by sensing microbe-associated molecular patterns (MAMPs) through pattern recognition receptors. Pattern recognition receptor complexes also have roles in cell death control, but the underlying mechanisms are poorly understood. Here, we report isolation of cerk1-4, a novel mutant allele of the Arabidopsis chitin receptor CERK1 with enhanced defense responses. We identified cerk1-4 in a forward genetic screen with barley powdery mildew and consequently characterized it by pathogen assays, mutant crosses and analysis of defense pathways. CERK1 and CERK1-4 proteins were analyzed biochemically. The cerk1-4 mutation causes an amino acid exchange in the CERK1 ectodomain. Mutant plants maintain chitin signaling capacity but exhibit hyper-inducible salicylic acid concentrations and deregulated cell death upon pathogen challenge. In contrast to chitin signaling, the cerk1-4 phenotype does not require kinase activity and is conferred by the N-terminal part of the receptor. CERK1 undergoes ectodomain shedding, a well-known process in animal cell surface proteins. Wild-type plants contain the full-length CERK1 receptor protein as well as a soluble form of the CERK1 ectodomain, whereas cerk1-4 plants lack the N-terminal shedding product. Our work suggests that CERK1 may have a chitin-independent role in cell death control and is the first report of ectodomain shedding in plants. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  15. Counter and Complicit Masculine Discourse Among Men’s Shed Members

    Science.gov (United States)

    Mackenzie, Corey S.; Roger, Kerstin; Robertson, Steve; Oliffe, John L.; Nurmi, Mary Anne; Urquhart, James

    2017-01-01

    Men’s Sheds is a growing international movement aimed at providing men with places and activities that facilitate social connectedness. Despite Men’s Sheds’ focus on males, little attention has been paid to masculinities within the specific context of these settings. The current study used a gender relations framework to explore the ways in which attendees discussed Men’s Sheds, with particular attention to discussions that were complicit and counter to traditional, hegemonic views of masculinity, and diverse positions in between these binaries. The data consisted of transcripts and field notes from four focus groups comprising mostly older, White, retired male members of a Canadian shed (N = 22). The analysis revealed three overall themes: (1) focus on work, (2) independence, and (3) need for male-focused spaces. These themes and associated subthemes suggest that shed members ascribe to dominant masculine values and ideals, but also support more fluid and flexible views of masculinity. Implications are discussed for how working with an array of masculinities within the Men’s Sheds movement will be helpful with respect to their future growth in Canada and internationally. PMID:28068851

  16. Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method.

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    Chao-Yie Yang

    Full Text Available The interleukin-1 receptor (IL-1R is the founding member of the interleukin 1 receptor family which activates innate immune response by its binding to cytokines. Reports showed dysregulation of cytokine production leads to aberrant immune cells activation which contributes to auto-inflammatory disorders and diseases. Current therapeutic strategies focus on utilizing antibodies or chimeric cytokine biologics. The large protein-protein interaction interface between cytokine receptor and cytokine poses a challenge in identifying binding sites for small molecule inhibitor development. Based on the significant conformational change of IL-1R type 1 (IL-1R1 ectodomain upon binding to different ligands observed in crystal structures, we hypothesized that transient small molecule binding sites may exist when IL-1R1 undergoes conformational transition and thus suitable for inhibitor development. Here, we employed accelerated molecular dynamics (MD simulation to efficiently sample conformational space of IL-1R1 ectodomain. Representative IL-1R1 ectodomain conformations determined from the hierarchy cluster analysis were analyzed by the SiteMap program which leads to identify small molecule binding sites at the protein-protein interaction interface and allosteric modulator locations. The cosolvent mapping analysis using phenol as the probe molecule further confirms the allosteric modulator site as a binding hotspot. Eight highest ranked fragment molecules identified from in silico screening at the modulator site were evaluated by MD simulations. Four of them restricted the IL-1R1 dynamical motion to inactive conformational space. The strategy from this study, subject to in vitro experimental validation, can be useful to identify small molecule compounds targeting the allosteric modulator sites of IL-1R and prevent IL-1R from binding to cytokine by trapping IL-1R in inactive conformations.

  17. Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis.

    Science.gov (United States)

    Genz, Berit; Nolden, Tobias; Negatsch, Alexandra; Teifke, Jens-Peter; Conzelmann, Karl-Klaus; Finke, Stefan

    2012-01-01

    The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV- and EBLV-2). These "envelope-switched" recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The "envelope-switched" RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.

  18. Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain

    International Nuclear Information System (INIS)

    Sun, Pei-Long; Lv, Shu-Xia; Zhou, Jian-Hua; Liu, Xin-Qi

    2011-01-01

    The equine infectious anaemia virus gp45 ectodomain was cloned, expressed and crystallized. Preliminary crystallographic analysis showed that the protein belonged to space group P6 3 and contained one molecule per asymmetric unit. Like human immunodeficiency virus (HIV), equine infectious anaemia virus (EIAV) belongs to the lentivirus genus. The first successful lentiviral vaccine was developed for EIAV. Thus, EIAV may serve as a valuable model for HIV vaccine research. EIAV glycoprotein 45 (gp45) plays a similar role to gp41 in HIV by mediating virus–host membrane fusion. The gp45 ectodomain was constructed according to the structure of HIV gp41, with removal of the disulfide-bond loop region. The protein was expressed in Escherichia coli and crystallized following purification. However, most of the crystals grew as aggregates and could not be used for data collection. By extensively screening hundreds of crystals, a 2.7 Å resolution data set was collected from a single crystal. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 46.84, c = 101.61 Å, α = β = 90, γ = 120°. Molecular replacement was performed using the coordinates of various lengths of HIV gp41 as search models. A long bent helix was identified and a well defined electron-density map around the long helix was obtained. This primary model provided the starting point for further refinement

  19. Engineering of Specific Tissue Inhibitors to Block ADAM Type Metalloprotease-Mediated Mammary Neoplasia

    Science.gov (United States)

    2001-07-01

    of the shedding en- References and Notes es. First, all ectodomain shedding is inhibit- zymes. Recently TACE was shown to be 1. J. Arribas , F. Lopez...apoptosis 1s. R. Brachmann et ala , Cell 56, 691 (1989). zyme or makes the cleavage site available, in lymphoid cell (21). 16. j. Kahn et al. Cell, 92

  20. Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread

    Science.gov (United States)

    Henaux, Viviane; Samuel, Michael D.

    2011-01-01

    Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10–11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive

  1. Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Thea Bismo Strøm

    2014-01-01

    Full Text Available More than 1700 mutations in the low density lipoprotein receptor (LDLR gene have been found to cause familial hypercholesterolemia (FH. These are commonly divided into five classes based upon their effects on the structure and function of the LDLR. However, little is known about the mechanism by which mutations in the transmembrane domain of the LDLR gene cause FH. We have studied how the transmembrane mutation G805R affects the function of the LDLR. Based upon Western blot analyses of transfected HepG2 cells, mutation G805R reduced the amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum. This led to reduced amounts of the mature 160 kDa LDLR at the cell surface. However, significant amounts of a secreted 140 kDa G805R-LDLR ectodomain fragment was observed in the culture media. Treatment of the cells with the metalloproteinase inhibitor batimastat largely restored the amounts of the 120 and 160 kDa forms in cell lysates, and prevented secretion of the 140 kDa ectodomain fragment. Together, these data indicate that a metalloproteinase cleaved the ectodomain of the 120 kDa precursor G805R-LDLR in the endoplasmic reticulum. It was the presence of the polar Arg805 and not the lack of Gly805 which led to ectodomain cleavage. Arg805 also prevented γ-secretase cleavage within the transmembrane domain. It is conceivable that introducing a charged residue within the hydrophobic membrane lipid bilayer, results in less efficient incorporation of the 120 kDa G805R-LDLR in the endoplasmic reticulum membrane and makes it a substrate for metalloproteinase cleavage.

  2. X-ray Structure of the Mature Ectodomain of Phogrin

    Energy Technology Data Exchange (ETDEWEB)

    Noguera, M. E. [National Univ. of Quilmes, Buenos Aires (Argentina); Primo, M. [Univ. of Buenos Aires (Argentina); Jakoncic, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Poskus, E. [Univ. of Buenos Aires (Argentina); Solimena, M. [Dresden Univ. of Technology and Max Planck Inst. of Molecular Cell Biology and Genetics (Germany); Ermacora, M. R. [National Univ. of Quilmes and Multidisciplinary Inst. of Cellular Biology, Buenos Aires (Argentina)

    2014-11-26

    Phogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure–function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Likewise to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel β-strands packed against two α-helices. Furthermore, sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.

  3. 77 FR 53884 - Automatic Underfrequency Load Shedding and Load Shedding Plans Reliability Standards; Notice of...

    Science.gov (United States)

    2012-09-04

    ... Underfrequency Load Shedding and Load Shedding Plans Reliability Standards; Notice of Compliance Filing Take notice that on August 9, 2012, North American Electric Reliability Corporation submitted a compliance... Load Shedding Plans Reliability Standards, 139 FERC ] 61,098, (Order No. 763) (2012). Any person...

  4. Antiplectin autoantibodies in subepidermal blistering diseases

    NARCIS (Netherlands)

    Buijsrogge, J. J. A.; de Jong, M. C. J. M.; Kloosterhuis, G. J.; Vermeer, M. H.; Koster, J.; Sonnenberg, A.; Jonkman, M. F.; Pas, H. H.

    2009-01-01

    Background Hemidesmosomal proteins may become targets of autoimmunity in subepidermal blistering diseases. Well-known recognized autoantigens are the intracellular plaque protein BP230, the transmembrane BP180 and its shed ecto-domain LAD-1. Objectives To establish the prevalence of autoimmunity

  5. The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.

    Directory of Open Access Journals (Sweden)

    Vey Hadinoto

    2009-07-01

    Full Text Available To develop more detailed models of EBV persistence we have studied the dynamics of virus shedding in healthy carriers. We demonstrate that EBV shedding into saliva is continuous and rapid such that the virus level is replaced in < or =2 minutes, the average time that a normal individual swallows. Thus, the mouth is not a reservoir of virus but a conduit through which a continuous flow stream of virus passes in saliva. Consequently, virus is being shed at a much higher rate than previously thought, a level too high to be accounted for by replication in B cells in Waldeyer's ring alone. Virus shedding is relatively stable over short periods (hours-days but varies through 3.5 to 5.5 logs over longer periods, a degree of variation that also cannot be accounted for solely by replication in B cells. This variation means, contrary to what is generally believed, that the definition of high and low shedder is not so much a function of variation between individuals but within individuals over time. The dynamics of shedding describe a process governing virus production that is occurring independently < or =3 times at any moment. This process grows exponentially and is then randomly terminated. We propose that these dynamics are best explained by a model where single B cells sporadically release virus that infects anywhere from 1 to 5 epithelial cells. This infection spreads at a constant exponential rate and is terminated randomly, resulting in infected plaques of epithelial cells ranging in size from 1 to 10(5 cells. At any one time there are a very small number (< or =3 of plaques. We suggest that the final size of these plaques is a function of the rate of infectious spread within the lymphoepithelium which may be governed by the structural complexity of the tissue but is ultimately limited by the immune response.

  6. Coxiella burnetii shedding by dairy cows.

    Science.gov (United States)

    Guatteo, Raphaël; Beaudeau, François; Joly, Alain; Seegers, Henri

    2007-01-01

    While shedding routes of Coxiella burnetii are identified, the characteristics of Coxiella shedding are still widely unknown, especially in dairy cattle. However, this information is crucial to assess the natural course of Coxiella burnetii infection within a herd and then to elaborate strategies to limit the risks of transmission between animals and to humans. The present study aimed at (i) describing the characteristics of Coxiella burnetii shedding by dairy cows (in milk, vaginal mucus, faeces) in five infected dairy herds, and at (ii) investigating the possible relationships between shedding patterns and serological responses. A total of 145 cows were included in a follow-up consisting of seven concomitant samplings of milk, vaginal mucus, faeces and blood (Day 0, D7, D14, D21, D28, D63, D90). Detection and quantification of Coxiella burnetii titres were performed in milk, vaginal mucus and faeces samples using real-time PCR assay, while antibodies against Coxiella were detected using an ELISA technique. For a given shedding route, and a given periodicity (weekly or monthly), cows were gathered into different shedding kinetic patterns according to the sequence of PCR responses. Distribution of estimated titres in Coxiella burnetii was described according to shedding kinetic patterns. Coxiella burnetii shedding was found scarcely and sporadically in faeces. Vaginal mucus shedding concerned almost 50% of the cows studied and was found intermittently or sporadically, depending on the periodicity considered. Almost 40% of cows were detected as milk shedders, with two predominant shedding patterns: persistent and sporadic, regardless of the sampling periodicity. Significantly higher estimated titres in Coxiella burnetii were observed in cows with persistent shedding patterns suggesting the existence of heavy shedder cows. These latter cows were mostly, persistently highly-seropositive, suggesting that repeated serological testings could be a reliable tool to screen

  7. Role of post-translational modifications at the β-subunit ectodomain in complex association with a promiscuous plant P4-ATPase.

    Science.gov (United States)

    Costa, Sara R; Marek, Magdalena; Axelsen, Kristian B; Theorin, Lisa; Pomorski, Thomas G; López-Marqués, Rosa L

    2016-06-01

    P-type ATPases of subfamily IV (P4-ATPases) constitute a major group of phospholipid flippases that form heteromeric complexes with members of the Cdc50 (cell division control 50) protein family. Some P4-ATPases interact specifically with only one β-subunit isoform, whereas others are promiscuous and can interact with several isoforms. In the present study, we used a site-directed mutagenesis approach to assess the role of post-translational modifications at the plant ALIS5 β-subunit ectodomain in the functionality of the promiscuous plant P4-ATPase ALA2. We identified two N-glycosylated residues, Asn(181) and Asn(231) Whereas mutation of Asn(231) seems to have a small effect on P4-ATPase complex formation, mutation of evolutionarily conserved Asn(181) disrupts interaction between the two subunits. Of the four cysteine residues located in the ALIS5 ectodomain, mutation of Cys(86) and Cys(107) compromises complex association, but the mutant β-subunits still promote complex trafficking and activity to some extent. In contrast, disruption of a conserved disulfide bond between Cys(158) and Cys(172) has no effect on the P4-ATPase complex. Our results demonstrate that post-translational modifications in the β-subunit have different functional roles in different organisms, which may be related to the promiscuity of the P4-ATPase. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  8. A High-Resolution Proteomic Landscaping of Primary Human Dental Stem Cells: Identification of SHED- and PDLSC-Specific Biomarkers

    Directory of Open Access Journals (Sweden)

    Vasiliki Taraslia

    2018-01-01

    Full Text Available Dental stem cells (DSCs have emerged as a promising tool for basic research and clinical practice. A variety of adult stem cell (ASC populations can be isolated from different areas within the dental tissue, which, due to their cellular and molecular characteristics, could give rise to different outcomes when used in potential applications. In this study, we performed a high-throughput molecular comparison of two primary human adult dental stem cell (hADSC sub-populations: Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs and Periodontal Ligament Stem Cells (PDLSCs. A detailed proteomic mapping of SHEDs and PDLSCs, via employment of nano-LC tandem-mass spectrometry (MS/MS revealed 2032 identified proteins in SHEDs and 3235 in PDLSCs. In total, 1516 proteins were expressed in both populations, while 517 were unique for SHEDs and 1721 were exclusively expressed in PDLSCs. Further analysis of the recorded proteins suggested that SHEDs predominantly expressed molecules that are involved in organizing the cytoskeletal network, cellular migration and adhesion, whereas PDLSCs are highly energy-producing cells, vastly expressing proteins that are implicated in various aspects of cell metabolism and proliferation. Applying the Rho-GDI signaling pathway as a paradigm, we propose potential biomarkers for SHEDs and for PDLSCs, reflecting their unique features, properties and engaged molecular pathways.

  9. Shedding light on avian influenza H4N6 infection in mallards: modes of transmission and implications for surveillance.

    Directory of Open Access Journals (Sweden)

    Kaci K VanDalen

    Full Text Available BACKGROUND: Wild mallards (Anas platyrhychos are considered one of the primary reservoir species for avian influenza viruses (AIV. Because AIV circulating in wild birds pose an indirect threat to agriculture and human health, understanding the ecology of AIV and developing risk assessments and surveillance systems for prevention of disease is critical. METHODOLOGY/PRINCIPAL FINDINGS: In this study, mallards were experimentally infected with an H4N6 subtype of AIV by oral inoculation or contact with an H4N6 contaminated water source. Cloacal swabs, oropharyngeal swabs, fecal samples, and water samples were collected daily and tested by real-time RT-PCR (RRT-PCR for estimation of viral shedding. Fecal samples had significantly higher virus concentrations than oropharyngeal or cloacal swabs and 6 month old ducks shed significantly more viral RNA than 3 month old ducks regardless of sample type. Use of a water source contaminated by AIV infected mallards, was sufficient to transmit virus to naïve mallards, which shed AIV at higher or similar levels as orally-inoculated ducks. CONCLUSIONS: Bodies of water could serve as a transmission pathway for AIV in waterfowl. For AIV surveillance purposes, water samples and fecal samples appear to be excellent alternatives or additions to cloacal and oropharyngeal swabbing. Furthermore, duck age (even within hatch-year birds may be important when interpreting viral shedding results from experimental infections or surveillance. Differential shedding among hatch-year mallards could affect prevalence estimates, modeling of AIV spread, and subsequent risk assessments.

  10. A cross-sectional study of bacterial vaginosis, intravaginal practices and HIV genital shedding; implications for HIV transmission and women's health.

    Science.gov (United States)

    Alcaide, Maria L; Chisembele, Maureen; Malupande, Emeria; Arheart, Kristopher; Fischl, Margaret; Jones, Deborah L

    2015-11-09

    Bacterial vaginosis (BV) is associated with an increased risk of HIV transmission, and intravaginal practices (IVP) are an important risk factor for developing BV. The relationship between IVP, BV and HIV lower genital shedding, responsible for HIV transmission, has not been examined in women receiving antiretrovirals in Zambia. Cross-sectional study. Community Health Center in Lusaka, Zambia. Participants were HIV-infected women receiving antiretroviral therapy and engaging in IVP (n=128). Participants completed audio computer-administered self-interviews to assess IVP and underwent a vaginal examination. BV was diagnosed using Nugent criteria. HIV-1 lower genital shedding was assessed by measuring HIV-1 RNA in cervicovaginal lavages. Most women engaged in IVP daily (114, 89.0%) and 81 (63.3%) of the participants had BV. HIV-1 genital shedding was detected in 18 (14.2%) participants. BV was associated with daily use of IVP (prevalence ratio, PR=4.58, CI 1.26 to 16.64, p=0.02) and weekly use of traditional medicines for IVP (PR=1.33, CI 1.05 to 1.68, p=0.02). The only factor associated with HIV-1 lower genital shedding was plasma viraemia (PR=4.61, CI 2.02 to 10.54, pHIV shedding. Despite the frequency of IVP and high prevalence of BV, plasma viraemia was the primary factor associated with HIV lower genital shedding. These findings support early initiation of antiretrovirals as an HIV prevention tool. Given adverse health outcomes associated with BV, the association between frequent IVP and BV, and the powerful local norms and traditions encouraging IVP, there is a need for studies assessing culturally tailored interventions to decrease BV in high-prevalence settings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Role of post-translational modifications at the β-subunit ectodomain in complex association with a promiscuous plant P4-ATPase

    DEFF Research Database (Denmark)

    Costa, Sara; Marek, Magdalena; Axelsen, Kristian Buhl

    2016-01-01

    and can interact with several isoforms. In the present study, we used a site-directed mutagenesis approach to assess the role of post-translational modifications at the plant ALIS5 β-subunit ectodomain in the functionality of the promiscuous plant P4-ATPase ALA2. We identified two N-glycosylated residues......) compromises complex association, but the mutant β-subunits still promote complex trafficking and activity to some extent. In contrast, disruption of a conserved disulfide bond between Cys(158) and Cys(172) has no effect on the P4-ATPase complex. Our results demonstrate that post-translational modifications...

  12. Soluble CD163

    DEFF Research Database (Denmark)

    Møller, Holger J

    2012-01-01

    CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function o...

  13. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Armant, D Randall; Kilburn, Brian A; Petkova, Anelia; Edwin, Samuel S; Duniec-Dmuchowski, Zophia M; Edwards, Holly J; Romero, Roberto; Leach, Richard E

    2006-02-01

    Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts.

  14. Prevalence of fecal shedding of Salmonella organisms among captive green iguanas and potential public health implications.

    Science.gov (United States)

    Burnham, B R; Atchley, D H; DeFusco, R P; Ferris, K E; Zicarelli, J C; Lee, J H; Angulo, F J

    1998-07-01

    To determine prevalence of fecal shedding of Salmonella organisms among captive green iguanas (Iguana iguana). Cohort study. 12 captive green iguanas. Iguanas were isolated in an environmental chamber, and fecal samples were collected weekly for 10 consecutive weeks. Samples were incubated aerobically in tetrathionate broth for 18 to 24 hours. Aliquots were then transferred to Hektoen and Salmonella-Shigella agar plates and incubated for an additional 18 to 24 hours. Isolated colonies were subcultured on nutrient agar slants, and Salmonella isolates were serogrouped and serotyped. All 12 iguanas were found to be shedding Salmonella organisms at least once during the study, and multiple serotypes were isolated from 7 of the 12. Salmonella organisms were isolated from 88 of 106 (83%) fecal samples; 21 samples contained multiple Salmonella serotypes. Overall, 11 Salmonella serotypes were identified. In 74 of 100 instances, when a particular Salmonella serotype was isolated from an individual iguana, the same serotype was also isolated from a subsequent fecal sample from that iguana. Results suggested that most iguanas have a stable mixture of Salmonella serotypes in their intestinal tracts and intermittently or continuously shed Salmonella organisms in their feces. Veterinarians should advise their clients on precautions for reducing the risk of acquiring these organisms from their pets. Public health officials trying to determine whether an iguana is the source of a specific Salmonella serotype that caused infection in human patients should submit at least 3 fecal samples collected from the iguana 1 week apart for bacterial culture.

  15. Vortex Shedding Inside a Baffled Air Duct

    Science.gov (United States)

    Davis, Philip; Kenny, R. Jeremy

    2010-01-01

    Common in the operation of both segmented and un-segmented large solid rocket motors is the occurrence of vortex shedding within the motor chamber. A portion of the energy within a shed vortex is converted to acoustic energy, potentially driving the longitudinal acoustic modes of the motor in a quasi-discrete fashion. This vortex shedding-acoustic mode excitation event occurs for every Reusable Solid Rocket Motor (RSRM) operation, giving rise to subsequent axial thrust oscillations. In order to better understand this vortex shedding/acoustic mode excitation phenomena, unsteady CFD simulations were run for both a test geometry and the full scale RSRM geometry. This paper covers the results from the subscale geometry runs, which were based on work focusing on the RSRM hydrodynamics. Unsteady CFD simulation parameters, including boundary conditions and post-processing returns, are reviewed. The results were further post-processed to identify active acoustic modes and vortex shedding characteristics. Probable locations for acoustic energy generation, and subsequent acoustic mode excitation, are discussed.

  16. Goodbye, solar shed; Pfiat di, Solarstadl

    Energy Technology Data Exchange (ETDEWEB)

    Diermann, Ralph

    2012-07-01

    In southern Germany, farmers and conservationalists are fighting over new sheds equipped with photovoltaic roofs. The impending amendment of the EEG is expected to solve the conflict. The losers of the game will be the farmers as reimbursement for solar roofs on sheds will be lowered.

  17. The impact of load shedding on gender relations in heterosexual households in Mkoba north, Gweru, Zimbabwe: Implications for sustainable development

    Directory of Open Access Journals (Sweden)

    Manuku Mukoni

    2012-09-01

    Full Text Available This study explored the impact of load shedding on gender relations in heterosexual households. 20 couples were selected through judgmental sampling that was followed by network referencing; bringing the sample to 40 participants. Study was descriptive in nature. Questionnaires and interviews were used to collect data. Study reveals that load shedding have ripple effects in the social fabric of sustainable development through its impacts on gender relations. Load shedding is proving to be reproducing and maintaining gender relations of inequality, thus holding back sustainable development. Women are deprived control of areas that traditional belongs to them like the decision and control of energy use in the household giving men more power over women. Load shedding is increasing men’s time in the public sphere while women are tied more to the private sphere. For sustainable development to be achieved, household relationships should uphold the principles of sustainable development and gender equality is one of them. Empowerment of women and men in household energy uses will aid in opening up their ‘functioning space’. An understanding and appreciation of gender equality in the household will help men and women to be influential in the larger society leading to sustainable development.

  18. CRISP. Intelligent load shedding. Deliverable 1.5

    International Nuclear Information System (INIS)

    Gajic, Z.; Karlsson, D.; Ullah, N.R.; Okuboye, S.; Andrieu, C.; Carlsson, P.

    2005-08-01

    Load shedding has been used to mitigate the consequences of large disturbances in electric power systems, since the beginning of the electrification era. The way to execute the load shedding, i.e. open a circuit breaker, has hardly developed at all for a 100-year period. The modern society dependence on reliable electricity supply is continuously increasing. This means that the consequences of traditional load shedding are not acceptable. In the meantime computer and communication technology has developed tremendously. There is also a trend to use more and more intelligent control and less hardware, such as lines and generators, to provide the required level of reliability for the electric supply. Especially in power systems, and parts of power systems, comprising distributed generation, there seems to be a great potential to improve the overall cost/benefit-ratio for the desired level of reliability, by the use of intelligent load shedding. Intelligent load shedding is a means to improve power system stability, by providing an adapted load control along the distribution network, in situations where the power system otherwise would go unstable. The work with intelligent load shedding in this work package results in various technical principles of dedicated algorithms. These algorithms intend to bring a support tool for the operating system during critical situations. The main aspects are evaluating the right amount and location of power response for a given disturbance, and evaluating the right time response expected in order to comply with an acceptable stability recover. This time response is a main object in order to define appropriate ICT network enabling such a reliable implementation. A main problem of the intelligent load shedding is how to choose load to shed conveniently and quickly. There is a technical problem of finding the right level and location of the load to shed, and also an economical problem of giving incentives in order to have enough remote

  19. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R

    2008-01-01

    and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF-binding proteins......, and in epidermal growth factor receptor (EGFR) pathways, via ectodomain shedding of membrane-tethered EGFR ligands. These proteolytic events may regulate diverse cellular responses, such as altered cell differentiation, proliferation, migration, and invasion. ADAM12 may also regulate cell-cell and cell...... to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal physiology...

  20. The Role of ATP in the Regulation of NCAM Function

    DEFF Research Database (Denmark)

    Hübschmann, Martin; Skladchikova, Galina

    2008-01-01

    overlaps with the site of NCAM-FGFR interaction, and ATP is capable of disrupting NCAM-FGFR binding. This implies that NCAM signaling through FGFR can be regulated by ATP, which is supported by the observation that ATP can abrogate NCAM-induced neurite outgrowth. Finally, ATP can induce NCAM ectodomain...... shedding, possibly affecting the structural plasticity associated with learning and memory....

  1. Circadian disc shedding in Xenopus retina in vitro

    International Nuclear Information System (INIS)

    Flannery, J.G.; Fisher, S.K.

    1984-01-01

    To further examine the endogenous rhythm of disc shedding and phagocytosis observed in several species, adult Xenopus were entrained to a 12 hr light/12 hr dark cycle and then placed in constant darkness. At various times during a 3-day period of constant darkness, eyes were explanted and placed into culture medium, then processed for light and electron microscopy. A clear rhythmicity of disc shedding was observed, with pronounced peaks at the times light onset occurred in the original entrainment cycle. Modification of the HCO 3 - ion concentration in the medium was found to raise the amplitude of the peak of endogenous disc shedding. Explants maintained in culture medium containing deuterium oxide (a compound known to perturb circadian oscillators) were found to shed with a longer interval between peaks. The addition of the protein synthesis inhibitor, anisomycin, to this preparation suppressed the shedding rhythm. The action of anisomycin was investigated by autoradiographic examination of the pattern of 3 H-leucine uptake and protein synthesis by the explant. The findings suggest the presence of a circadian oscillator for rhythmic disc shedding within the amphibian eye

  2. Improved Load Shedding Scheme considering Distributed Generation

    DEFF Research Database (Denmark)

    Das, Kaushik; Nitsas, Antonios; Altin, Müfit

    2017-01-01

    With high penetration of distributed generation (DG), the conventional under-frequency load shedding (UFLS) face many challenges and may not perform as expected. This article proposes new UFLS schemes, which are designed to overcome the shortcomings of traditional load shedding scheme...

  3. Veje ind og ud af hjemløshed

    DEFF Research Database (Denmark)

    Benjaminsen, Lars; Enemark, Morten Holm

    Hjemløsheden i Danmark har været stigende i de seneste år. Denne rapport beskriver forløbene op mod hjemløshed, vejene gennem hjemløshed og chancerne for at komme ud af hjemløshed igen. På baggrund af data fra hjemløsetællingerne og fra landets herberger (§ 110-boformer) i perioden 2009-2015 anal...

  4. HydroSHEDS: A global comprehensive hydrographic dataset

    Science.gov (United States)

    Wickel, B. A.; Lehner, B.; Sindorf, N.

    2007-12-01

    The Hydrological data and maps based on SHuttle Elevation Derivatives at multiple Scales (HydroSHEDS) is an innovative product that, for the first time, provides hydrographic information in a consistent and comprehensive format for regional and global-scale applications. HydroSHEDS offers a suite of geo-referenced data sets, including stream networks, watershed boundaries, drainage directions, and ancillary data layers such as flow accumulations, distances, and river topology information. The goal of developing HydroSHEDS was to generate key data layers to support regional and global watershed analyses, hydrological modeling, and freshwater conservation planning at a quality, resolution and extent that had previously been unachievable. Available resolutions range from 3 arc-second (approx. 90 meters at the equator) to 5 minute (approx. 10 km at the equator) with seamless near-global extent. HydroSHEDS is derived from elevation data of the Shuttle Radar Topography Mission (SRTM) at 3 arc-second resolution. The original SRTM data have been hydrologically conditioned using a sequence of automated procedures. Existing methods of data improvement and newly developed algorithms have been applied, including void filling, filtering, stream burning, and upscaling techniques. Manual corrections were made where necessary. Preliminary quality assessments indicate that the accuracy of HydroSHEDS significantly exceeds that of existing global watershed and river maps. HydroSHEDS was developed by the Conservation Science Program of the World Wildlife Fund (WWF) in partnership with the U.S. Geological Survey (USGS), the International Centre for Tropical Agriculture (CIAT), The Nature Conservancy (TNC), and the Center for Environmental Systems Research (CESR) of the University of Kassel, Germany.

  5. Overexpression, crystallization and preliminary X-ray crystallographic analysis of the variable lymphocyte receptor 2913 ectodomain fused with internalin B

    International Nuclear Information System (INIS)

    Lee, Ji Yeon; Kim, Hyoun Sook; Baek, In Wha; Back, Jang Mi; Han, Mi Ra; Kong, Sun-Young; Kim, Ji Hyeon; Kirchdoerfer, Robert N.; Kim, Jae-Ouk; Cooper, Max D.; Wilson, Ian A.; Kim, Hyun-Jung; Han, Byung Woo

    2012-01-01

    The VLR2913 ectodomain fused with internalin B was crystallized and diffraction data were collected to a maximum resolution of 2.04 Å. In jawless vertebrates, variable lymphocyte receptors (VLRs) play a crucial role in the recognition of antigens as part of the adaptive immune system. Leucine-rich repeat (LRR) modules and the highly variable insert (HVI) of VLRs contribute to the specificity and diversity of antigen recognition. VLR2913, the antigen of which is not known, contains the same HVI amino-acid sequence as that of VLR RBC36, which recognizes the H-trisaccharide from human blood type O erythrocytes. Since the HVI sequence is rarely identical among all known VLRs, identification of the antigen for VLR2913 and the main contributing factors for antigen recognition based on a comparison of VLR2913 and VLR RBC36 has been attempted. To initiate and facilitate this structural approach, the ectodomain of VLR2913 was fused with the N-terminal domain of internalin B (InlB-VLR2913-ECD). Three amino-acid residues on the concave surface of the LRR modules of InlB-VLR2913-ECD were mutated, considering important residues for hydrogen bonds in the recognition of H-trisaccharide by VLR RBC36. InlB-VLR2913-ECD was overexpressed in Escherichia coli and was crystallized at 295 K using the sitting-drop vapour-diffusion method. X-ray diffraction data were collected to 2.04 Å resolution and could be indexed in the tetragonal space group P4 1 2 1 2 (or P4 3 2 1 2), with unit-cell parameters a = 91.12, b = 91.12, c = 62.87 Å. Assuming that one monomer molecule was present in the crystallographic asymmetric unit, the calculated Matthews coefficient (V M ) was 2.75 Å 3 Da −1 and the solvent content was 55.2%. Structural determination of InlB-VLR2913-ECD by molecular replacement is in progress

  6. Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yueying Liu

    2012-01-01

    Full Text Available Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA, a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

  7. Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.

    Directory of Open Access Journals (Sweden)

    Irina Lonskaya

    Full Text Available Matrix metalloproteinases (MMPs are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP, spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a β1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5, a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with β1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs. With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies

  8. Phthalate SHEDS-HT runs

    Data.gov (United States)

    U.S. Environmental Protection Agency — Inputs and outputs for SHEDS-HT runs of DiNP, DEHP, DBP. This dataset is associated with the following publication: Moreau, M., J. Leonard, K. Phillips, J. Campbell,...

  9. Numerical Simulations of Vortex Shedding in Hydraulic Turbines

    Science.gov (United States)

    Dorney, Daniel; Marcu, Bogdan

    2004-01-01

    Turbomachines for rocket propulsion applications operate with many different working fluids and flow conditions. Oxidizer boost turbines often operate in liquid oxygen, resulting in an incompressible flow field. Vortex shedding from airfoils in this flow environment can have adverse effects on both turbine performance and durability. In this study the effects of vortex shedding in a low-pressure oxidizer turbine are investigated. Benchmark results are also presented for vortex shedding behind a circular cylinder. The predicted results are compared with available experimental data.

  10. Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.

    Directory of Open Access Journals (Sweden)

    Helen M Wise

    Full Text Available Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42 with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.

  11. Load shedding scheme in the south/southeastern interconnected system

    Energy Technology Data Exchange (ETDEWEB)

    Vieira Filho, Xisto; Couri, J J.G.; Gomes, P; Almeida, P C [ELETROBRAS, Rio de Janeiro, RJ (Brazil)

    1988-12-31

    This paper presents some characteristics of the Brazilian interconnected system and discusses the load shedding scheme in its different stages considering the beginning of operation of the Itaipu power plant. The present situation of the South and Southeastern load shedding scheme combination is also commented. Finally, the interconnected system evolution and the effects on the load shedding schemes are discussed. 4 refs., 5 figs., 2 tabs.

  12. Nanoscale interfacial defect shedding in a growing nematic droplet.

    Science.gov (United States)

    Gurevich, Sebastian; Provatas, Nikolas; Rey, Alejandro

    2017-08-01

    Interfacial defect shedding is the most recent known mechanism for defect formation in a thermally driven isotropic-to-nematic phase transition. It manifests in nematic-isotropic interfaces going through an anchoring switch. Numerical computations in planar geometry established that a growing nematic droplet can undergo interfacial defect shedding, nucleating interfacial defect structures that shed into the bulk as +1/2 point defects. By extending the study of interfacial defect shedding in a growing nematic droplet to larger length and time scales, and to three dimensions, we unveil an oscillatory growth mode involving shape and anchoring transitions that results in a controllable regular distributions of point defects in planar geometry, and complex structures of disclination lines in three dimensions.

  13. Suppression of vortex shedding around a square cylinder using ...

    Indian Academy of Sciences (India)

    control of vortex shedding of square cylinders using blowing or suction. ... also showed complete suppression of vortex shedding if suction velocity falls between 0.40 .... equations such that mass balance (continuity) is satisfied simultaneously.

  14. Cell shedding from X-irradiated multicellular spheroids of human lung carcinomas

    International Nuclear Information System (INIS)

    Sakata, K.; Okada, S.; Suzuki, N.; Majima, H.

    1991-01-01

    We studied the effect of radiation on cell shedding from the surface of multicellular spheroids. Spheroids were produced from two human lung cell lines, one adenocarcinoma (LCT1) and the other small cell carcinoma (LCT2), by using a liquid overlay culture technique. The number of cells shed from both kinds of spheroids did not change significantly when they were irradiated. The number of clonogenic cells shed from both kinds of irradiated spheroids decreased sharply as the dose of irradiation increases. There were no significant differences in clonogenic cell shedding per spheroid between LCT1 and LCT2 spheroids. 400 μm spheroids were more radioresistant to inhibition of clonogenic cell shedding than 250 μm spheroids. Shed cells were more radiosensitive than speroid cells. In these experiments, we did not obtain any results indicating that radiation enchances metastasis. (orig.) [de

  15. Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1

    Directory of Open Access Journals (Sweden)

    Takako Saito

    2017-05-01

    Full Text Available Endoglin (ENG/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1 and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9. BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.

  16. Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

    Science.gov (United States)

    Spencer, LaShonda Y; Christiansen, Shawna; Wang, Chia-Hao H; Mack, Wendy J; Young, Mary; Strickler, Howard D; Anastos, Kathryn; Minkoff, Howard; Cohen, Mardge; Geenblatt, Ruth M; Karim, Roksana; Operskalski, Eva; Frederick, Toni; Homans, James D; Landay, Alan; Kovacs, Andrea

    2016-02-01

    Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV

  17. 76 FR 66220 - Automatic Underfrequency Load Shedding and Load Shedding Plans Reliability Standards

    Science.gov (United States)

    2011-10-26

    .... I. Background A. Underfrequency Load Shedding 4. An interconnected electric power system must... generation and load within an interconnected electric power system is shown in the frequency of the system.\\4... Reliability Standards for the Bulk-Power System, Order No. 693, FERC Stats. & Regs. ] 31,242, order on reh'g...

  18. Periodic cavitation shedding in a cylindrical orifice

    Energy Technology Data Exchange (ETDEWEB)

    Stanley, C.; Barber, T.; Milton, B.; Rosengarten, G. [University of New South Wales, School of Mechanical and Manufacturing Engineering, Sydney (Australia)

    2011-11-15

    Cavitation structures in a large-scale (D = 8.25 mm), plain orifice style nozzle within a unique experimental rig are investigated using high-speed visualisation and digital image processing techniques. Refractive index matching with an acrylic nozzle is achieved using aqueous sodium iodide for the test fluid. Cavitation collapse length, unsteady shedding frequency and spray angles are measured for cavitation conditions from incipient to supercavitation for a range of Reynolds numbers, for a fixed L/D ratio of 4.85. Periodic cavitation shedding was shown to occur with frequencies between 500 and 2,000 Hz for conditions in which cavitation occupied less than 30% of the nozzle length. A discontinuity in collapse length was shown to occur once the cavitation exceeded this length, coinciding with a loss of periodic shedding. A mechanism for this behaviour is discussed. Peak spray angles of approximately {theta} {approx} 14 were recorded for supercavitation conditions indicating the positive influence of cavitation bubble collapse on the jet atomisation process. (orig.)

  19. The Role of Collaborative Learning on Training and Development Practices within the Australian Men's Shed Movement: A Study of Five Men's Sheds

    Science.gov (United States)

    Cavanagh, Jillian; Southcombe, Amie; Bartram, Tim

    2014-01-01

    This study examines the role and impact of collaborative learning on training and development practices in Australian Men's Sheds. We use a case study approach, underpinned by Peters and Armstrong's theoretical framework of collaborative learning in adult education, to investigate five Men's Sheds. Semi-structured interviews were carried out with…

  20. Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

    Science.gov (United States)

    Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael

    2017-01-01

    Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV

  1. Syndecans in heart fibrosis.

    Science.gov (United States)

    Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir

    2016-09-01

    Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing

  2. Experimental investigation on cavitating flow shedding over an axisymmetric blunt body

    Science.gov (United States)

    Hu, Changli; Wang, Guoyu; Huang, Biao

    2015-03-01

    Nowadays, most researchers focus on the cavity shedding mechanisms of unsteady cavitating flows over different objects, such as 2D/3D hydrofoils, venturi-type section, axisymmetric bodies with different headforms, and so on. But few of them pay attention to the differences of cavity shedding modality under different cavitation numbers in unsteady cavitating flows over the same object. In the present study, two kinds of shedding patterns are investigated experimentally. A high speed camera system is used to observe the cavitating flows over an axisymmetric blunt body and the velocity fields are measured by a particle image velocimetry (PIV) technique in a water tunnel for different cavitation conditions. The U-type cavitating vortex shedding is observed in unsteady cavitating flows. When the cavitation number is 0.7, there is a large scale cavity rolling up and shedding, which cause the instability and dramatic fluctuation of the flows, while at cavitation number of 0.6, the detached cavities can be conjunct with the attached part to induce the break-off behavior again at the tail of the attached cavity, as a result, the final shedding is in the form of small scale cavity and keeps a relatively steady flow field. It is also found that the interaction between the re-entrant flow and the attached cavity plays an important role in the unsteady cavity shedding modality. When the attached cavity scale is insufficient to overcome the re-entrant flow, it deserves the large cavity rolling up and shedding just as that at cavitation number of 0.7. Otherwise, the re-entrant flow is defeated by large enough cavity to induce the cavity-combined process and small scale cavity vortexes shedding just as that of the cavitation number of 0.6. This research shows the details of two different cavity shedding modalities which is worthful and meaningful for the further study of unsteady cavitation.

  3. Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

    Science.gov (United States)

    Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

    2017-09-24

    We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

  4. Capacity building in indigenous men's groups and sheds across Australia.

    Science.gov (United States)

    Southcombe, Amie; Cavanagh, Jillian; Bartram, Timothy

    2015-09-01

    This article presents an investigation into capacity building, at the community level, in Aboriginal and Torres Strait Islander Men's Groups and Sheds. As safe men's spaces, Men's Groups and Sheds represent an ever-growing social, and health and well-being community service across Australia. The study is qualitative and employs 'yarning circles' (focus groups), semi-structured interviews and observations to gather data from 15 Groups/Sheds involving 45 men from urban, regional and remote communities. We found that capacity building is primarily about securing relationships between Group Leaders/Shed Co-ordinators and Government services. Capacity building establishes links to services such as Centrelink, Medicare, Department of Housing, Probation and Control, and positive outcomes such as Indigenous men securing housing and Centrelink payments. Capacity building results in better health outcomes and, educates and empowers men to improve their social, cultural, emotional and economic well-being. It helps men to better connect with family and community. The current research paves the way for countries worldwide to explore the conceptual and empirical approach of capacity building applicable to other Indigenous [and non-Indigenous] Men's Groups/Sheds. We recommend feasibilities studies, on approaches to capacity building in Indigenous Groups/Sheds, be carried out within urban, regional and remote regions across the country. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Salmonella fecal shedding and immune responses are dose- and serotype- dependent in pigs.

    Directory of Open Access Journals (Sweden)

    Renata Ivanek

    Full Text Available Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding and two non-shedding (latency and intermittent non-shedding, and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×10(6 CFU/pig and high (0.65×10(9 CFU/pig] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10-26 days longer, while intermittent non-shedding was 2-4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10-17 and 3-4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8-11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of

  6. The membrane-proximal tryptophan-rich region in the transmembrane glycoprotein ectodomain of feline immunodeficiency virus is important for cell entry

    International Nuclear Information System (INIS)

    Giannecchini, Simone; Bonci, Francesca; Pistello, Mauro; Matteucci, Donatella; Sichi, Olimpia; Rovero, Paolo; Bendinelli, Mauro

    2004-01-01

    The mechanisms whereby feline immunodeficiency virus (FIV) adsorbs and enters into susceptible cells are poorly understood. Here, we investigated the role exerted in such functions by the tryptophan (Trp)-rich motif present membrane-proximally in the ectodomain of the FIV transmembrane glycoprotein. Starting from p34TF10, which encodes the entire genome of FIV Petaluma, we produced 11 mutated clones having the Trp-rich motif scrambled or variously deleted or substituted. All mutated progenies adsorbed normally to cells, but the ones with severe disruptions of the motif failed to generate proviral DNA. In the latter mutants, proviral DNA formation was restored by providing an independent source of intact FIV envelope glycoproteins or by addition of the fusing agent polyethylene glycol, thus clearly indicating that their defect resided primarily at the level of cell entry. In addition, the replication-competent mutants exhibited a generally enhanced susceptibility to selected entry inhibitory synthetic peptides, suggestive of a reduced efficiency of the entry step

  7. Protoearth mass shedding and the origin of the moon

    Science.gov (United States)

    Boss, A. P.

    1986-01-01

    Darwin's (1980) theory of lunar formation from the earth by means of a rotationally driven dynamic fission instability is presently considered in view of viscous shear's maintenance of solid body rotation throughout the protoearth's accretion phase. Assuming the appropriateness of a polytropic account of the protoearth, it is unlikely that dynamic fission could have occurred; instantaneous spin-up following a giant impact would instead have led to mass shedding. The dynamical phenomenon of mass shedding is here explored on the basis of numerical models for a self-gravitating, axisymmetric, polytropic and dissipative protoearth. It is concluded that mass shedding from the protoearth mantle after a giant impact and explosion could have contributed substantial matter to a lunar disk.

  8. Two-Stage Load Shedding for Secondary Control in Hierarchical Operation of Islanded Microgrids

    DEFF Research Database (Denmark)

    Zhou, Quan; Li, Zhiyi; Wu, Qiuwei

    2018-01-01

    A two-stage load shedding scheme is presented to cope with the severe power deficit caused by microgrid islanding. Coordinated with the fast response of inverter-based distributed energy resources (DERs), load shedding at each stage and the resulting power flow redistribution are estimated....... The first stage of load shedding will cease rapid frequency decline in which the measured frequency deviation is employed to guide the load shedding level and process. Once a new steady-state is reached, the second stage is activated, which performs load shedding according to the priorities of loads...

  9. Review of the Phenomenon of Ice Shedding from Wind Turbine Blades

    Directory of Open Access Journals (Sweden)

    H Xue

    2016-08-01

    Full Text Available Wind power is a sustainable source of energy. However, there are certain challenges to be  overcome. One of the operational challenges is the phenomenon of ice shedding. Icing happens on wind turbine blades in cold regions. When ice grows to a certain size, it separates from the wind turbine blades resulting in the phenomenon of ice shedding. This phenomenon is of significantly dangerous for equipment and personnel in the region. Ice shedding may happen either because of vibrations or bending in blades. However, it was noticed by operators at Nygårdsfjell wind park, Narvik, Norway that ice shedding is more probable to happen when blades are stopped and turned back on. This observation reveals the fact that bending of blades (from loaded to unloaded positions allows the ice to separate and hence result in ice shedding. This can be linked to the phenomenon of icing, mechanical and adhesive properties of ice. This paper reviews above in detail.

  10. Stochastic oscillations induced by vortex shedding in wind

    DEFF Research Database (Denmark)

    Christensen, Claus

    1997-01-01

    As a fluid flows past a circular cylinder,vortices are shed alternately from each side at most values of the Reynolds number. Over a certain range of windspeeds, the periodicity in the wake is synchronized or captured by the mechanical system. The shedding abruptly deviates from the linear Strouhal...... dependence and stays constant at the mechanical natural frequency. This coupling between the velocity field and the motion of the mechanical system is referred to as the lock-in phenomenon. The lock-in phenomenon has importance in structural engineering for slightly damped slender structures exposed to wind...... in the wake is synchronized or captured by the mechanical system. The shedding abruptly deviates from the linear Strouhal dependence and stays constant at the mechanical natural frequency. This coupling between the velocity field and the motion of the mechanical system is referred to as the lock-in phenomenon...

  11. The Transition from Thick to Thin Plate Wake Physics: Whither Vortex Shedding?

    Science.gov (United States)

    Rai, Man Mohan

    2016-01-01

    The near and very near wake of a flat plate with a circular trailing edge is investigated with data from direct numerical simulations. Computations were performed for six different combinations of the Reynolds numbers based on plate thickness (D) and boundary layer momentum thickness upstream of the trailing edge (theta). Unlike the case of the cylinder, these Reynolds numbers are independent parameters for the flat plate. The separating boundary layers are turbulent in all the cases investigated. One objective of the study is to understand the changes in the wake vortex shedding process as the plate thickness is reduced (increasing theta/D). The value of D varies by a factor of 16 and that of theta by approximately 5 in the computations. Vortex shedding is vigorous in the low theta/D cases with a substantial decrease in shedding intensity in the large theta/D cases. Other shedding characteristics are also significantly altered with increasing theta/D. A visualization of the shedding process in the different cases is provided and discussed. The basic shedding mechanism is explored in depth. The effect of changing theta/D on the time-averaged, near-wake velocity statistics is also discussed. A functional relationship between the shedding frequency and the Reynolds numbers mentioned above is obtained.

  12. Men's Sheds function and philosophy: towards a framework for future research and men's health promotion.

    Science.gov (United States)

    Wilson, Nathan J; Cordier, Reinie; Doma, Kenji; Misan, Gary; Vaz, Sharmila

    2015-08-01

    The Men's Shed movement supports a range of men's health promotion initiatives. This paper examines whether a Men's Shed typology could inform future research and enable more efficient and targeted health promotion activities through Men's Sheds. The International Men's Shed Survey consisted of a cross-sectional exploration of sheds, their members, and health and social activities. Survey data about shed 'function' and 'philosophy' were analysed using descriptive and inferential statistics. A framework of Men's Sheds based on function and philosophy demonstrated that most sheds serve a primary utility function, a secondary social function, but most importantly a primary social opportunity philosophy. Sheds with a primary health philosophy participated in fewer health promotion activities when compared with sheds without a primary health philosophy. In addition to the uniform health promotion resources distributed by the Men's Shed associations, specific health promotion activities, such as prostate education, are being initiated from an individual shed level. This framework can potentially be used to enable future research and health promotion activities to be more efficiently and effectively targeted. SO WHAT? Men experience poorer health and well being outcomes than women. This framework offers a novel approach to providing targeted health promotion activities to men in an environment where it is okay to talk about men's health.

  13. Influence of particle shedding from silicone tubing on antibody stability.

    Science.gov (United States)

    Saller, Verena; Hediger, Constanze; Matilainen, Julia; Grauschopf, Ulla; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

    2018-05-01

    Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product. Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2-8, 25 and 40°C were conducted. Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo. Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability. © 2016 Royal Pharmaceutical Society.

  14. Genetic relationship between wool shedding in ewe-lambs and ewes

    Science.gov (United States)

    Interest in reducing labor costs related to shearing has led to the development of breeds that naturally shed their wool annually. This goal has been achieved by introducing hair-sheep genetics. These developments are relatively recent and thus the genetic underpinnings of wool shedding (WS) are not...

  15. Developing of the EV charging and parking shed of BIPV

    Institute of Scientific and Technical Information of China (English)

    Wu Shaobo; Wei Chuanchuan; Yu Jiang

    2013-01-01

    Building-integrated photovoltaic (BIPV) is an important application way of solar photovoltaic power. The electric vehicle (EV) charging and parking shed of BIPV is the regeneration energy intellectual integration demonstration application system collection of photovoltaic (PV) grid power,PV off-grid power,EV charging and parking shed,and any part of the functions and their combination will be engaged in practical application on demand. The paper describes the PV shed system structure and design in detail with the present of its actual photos. The shed is 50 m long and 5.5 m wide and capable of parking 18 cars. Under the control of system intellectual con-troller,the power produced by PV from sunlight will charge the parking EV car prior to charging the storage bat-tery,charging the storage battery prior to grid power,grid power at last,and charge the EV by utility grid when it is a cloudy or rainy day.

  16. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

    Science.gov (United States)

    Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L; Sanders, Eduard J; Peshu, Norbert M; Krieger, John N; Muller, Charles H; Coombs, Robert W; Fredricks, David N; Graham, Susan M

    2017-03-01

    HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

  17. Application of computational intelligence techniques for load shedding in power systems: A review

    International Nuclear Information System (INIS)

    Laghari, J.A.; Mokhlis, H.; Bakar, A.H.A.; Mohamad, Hasmaini

    2013-01-01

    Highlights: • The power system blackout history of last two decades is presented. • Conventional load shedding techniques, their types and limitations are presented. • Applications of intelligent techniques in load shedding are presented. • Intelligent techniques include ANN, fuzzy logic, ANFIS, genetic algorithm and PSO. • The discussion and comparison between these techniques are provided. - Abstract: Recent blackouts around the world question the reliability of conventional and adaptive load shedding techniques in avoiding such power outages. To address this issue, reliable techniques are required to provide fast and accurate load shedding to prevent collapse in the power system. Computational intelligence techniques, due to their robustness and flexibility in dealing with complex non-linear systems, could be an option in addressing this problem. Computational intelligence includes techniques like artificial neural networks, genetic algorithms, fuzzy logic control, adaptive neuro-fuzzy inference system, and particle swarm optimization. Research in these techniques is being undertaken in order to discover means for more efficient and reliable load shedding. This paper provides an overview of these techniques as applied to load shedding in a power system. This paper also compares the advantages of computational intelligence techniques over conventional load shedding techniques. Finally, this paper discusses the limitation of computational intelligence techniques, which restricts their usage in load shedding in real time

  18. The Gamma-Ray Burst ToolSHED is Open for Business

    Science.gov (United States)

    Giblin, Timothy W.; Hakkila, Jon; Haglin, David J.; Roiger, Richard J.

    2004-09-01

    The GRB ToolSHED, a Gamma-Ray Burst SHell for Expeditions in Data-Mining, is now online and available via a web browser to all in the scientific community. The ToolSHED is an online web utility that contains pre-processed burst attributes of the BATSE catalog and a suite of induction-based machine learning and statistical tools for classification and cluster analysis. Users create their own login account and study burst properties within user-defined multi-dimensional parameter spaces. Although new GRB attributes are periodically added to the database for user selection, the ToolSHED has a feature that allows users to upload their own burst attributes (e.g. spectral parameters, etc.) so that additional parameter spaces can be explored. A data visualization feature using GNUplot and web-based IDL has also been implemented to provide interactive plotting of user-selected session output. In an era in which GRB observations and attributes are becoming increasingly more complex, a utility such as the GRB ToolSHED may play an important role in deciphering GRB classes and understanding intrinsic burst properties.

  19. Comparison of three nonlinear models to describe long-term tag shedding by lake trout

    Science.gov (United States)

    Fabrizio, Mary C.; Swanson, Bruce L.; Schram, Stephen T.; Hoff, Michael H.

    1996-01-01

    We estimated long-term tag-shedding rates for lake trout Salvelinus namaycush using two existing models and a model we developed to account for the observed permanence of some tags. Because tag design changed over the course of the study, we examined tag-shedding rates for three types of numbered anchor tags (Floy tags FD-67, FD-67C, and FD-68BC) and an unprinted anchor tag (FD-67F). Lake trout from the Gull Island Shoal region, Lake Superior, were double-tagged, and subsequent recaptures were monitored in annual surveys conducted from 1974 to 1992. We modeled tag-shedding rates, using time at liberty and probabilities of tag shedding estimated from fish released in 1974 and 1978–1983 and later recaptured. Long-term shedding of numbered anchor tags in lake trout was best described by a nonlinear model with two parameters: an instantaneous tag-shedding rate and a constant representing the proportion of tags that were never shed. Although our estimates of annual shedding rates varied with tag type (0.300 for FD-67, 0.441 for FD-67C, and 0.656 for FD-68BC), differences were not significant. About 36% of tags remained permanently affixed to the fish. Of the numbered tags that were shed (about 64%), two mechanisms contributed to tag loss: disintegration and dislodgment. Tags from about 11% of recaptured fish had disintegrated, but most tags were dislodged. Unprinted tags were shed at a significant but low rate immediately after release, but the long-term, annual shedding rate of these tags was only 0.013. Compared with unprinted tags, numbered tags dislodged at higher annual rates; we hypothesized that this was due to the greater frictional drag associated with the larger cross-sectional area of numbered tags.

  20. Men's re-placement: Social practices in a Men's Shed.

    Science.gov (United States)

    Anstiss, David; Hodgetts, Darrin; Stolte, Ottilie

    2018-05-06

    Transitions into retirement can be difficult at the best of times. Many men find themselves having to reflect on who they are and what their lives are about. Their access to social supports and material resources are often disrupted. Men's Sheds offer a space where retired men can actively pursue wellbeing, and respond to disruption and loneliness through emplaced community practices. This paper draws on ethnographic research in a Men's Shed in Auckland, New Zealand in order to explore the social practices through which men create a shared space for themselves in which they can engage in meaningful relationships with each other. We document how participants work in concert to create a space in which they can be together through collective labour. Their emplacement in the shed affords opportunities for supported transitions into retirement and for engaging healthy lives beyond paid employment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1–Seropositive Kenyan Men

    Science.gov (United States)

    Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L.; Sanders, Eduard J.; Peshu, Norbert M.; Krieger, John N.; Muller, Charles H.; Coombs, Robert W.; Fredricks, David N.; Graham, Susan M.

    2017-01-01

    Introduction: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. Methods: We analyzed semen samples from 42 HIV-1–seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Results: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: −0.77, 95% CI: −1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Conclusion: Most of these HIV-1–infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission. PMID:27861240

  2. A bankruptcy problem approach to load-shedding in multiagent-based microgrid operation.

    Science.gov (United States)

    Kim, Hak-Man; Kinoshita, Tetsuo; Lim, Yujin; Kim, Tai-Hoon

    2010-01-01

    A microgrid is composed of distributed power generation systems (DGs), distributed energy storage devices (DSs), and loads. To maintain a specific frequency in the islanded mode as an important requirement, the control of DGs' output and charge action of DSs are used in supply surplus conditions and load-shedding and discharge action of DSs are used in supply shortage conditions. Recently, multiagent systems for autonomous microgrid operation have been studied. Especially, load-shedding, which is intentional reduction of electricity use, is a critical problem in islanded microgrid operation based on the multiagent system. Therefore, effective schemes for load-shedding are required. Meanwhile, the bankruptcy problem deals with dividing short resources among multiple agents. In order to solve the bankruptcy problem, division rules, such as the constrained equal awards rule (CEA), the constrained equal losses rule (CEL), and the random arrival rule (RA), have been used. In this paper, we approach load-shedding as a bankruptcy problem. We compare load-shedding results by above-mentioned rules in islanded microgrid operation based on wireless sensor network (WSN) as the communication link for an agent's interactions.

  3. Proteolysis of platelet receptors in humans and other species.

    Science.gov (United States)

    Qiao, Jian L; Shen, Yang; Gardiner, Elizabeth E; Andrews, Robert K

    2010-08-01

    In the past 5 years, metalloproteinase-mediated ectodomain shedding of platelet receptors has emerged as a new mechanism for modulating platelet function. By regulating surface expression of the platelet-specific receptors, glycoprotein (GP)VI that binds collagen, and GPIbalpha (the major ligand-binding subunit of the GPIb-IX-V complex) that binds von Willebrand factor (VWF) and other procoagulant and proinflammatory ligands, shedding not only irreversibly downregulates GPVI/GPIbalpha function, but generates proteolytic fragments that might be unique biomarkers or modulators in plasma. This is potentially significant because GPVI and GPIbalpha are involved in initiating thrombotic diseases such as heart attack and stroke, as well as autoimmune diseases where anti-platelet antibodies result in thrombocytopenia. Altered expression levels of GPIbalpha/GPVI are associated with both thrombotic propensity and platelet aging, suggesting an additional role in platelet clearance. Although emerging data are elucidating molecular mechanisms underlying GPIbalpha/GPVI shedding, evidence for the functional consequences of shedding in vivo, either clinically or in animal models, is far more limited. Here we consider recent published evidence for GPVI or GPIbalpha shedding in humans, nonhuman primates and mice, and whether conservation of sheddase cleavage sites across species points to a functional role for metalloproteolytic shedding in vivo.

  4. Circulation shedding in viscous starting flow past a flat plate

    International Nuclear Information System (INIS)

    Nitsche, Monika; Xu, Ling

    2014-01-01

    Numerical simulations of viscous flow past a flat plate moving in the direction normal to itself reveal details of the vortical structure of the flow. At early times, most of the vorticity is attached to the plate. This paper introduces a definition of the shed circulation at all times and shows that it indeed represents vorticity that separates and remains separated from the plate. During a large initial time period, the shed circulation satisfies the scaling laws predicted for self-similar inviscid separation. Various contributions to the circulation shedding rate are presented. The results show that during this initial time period, viscous diffusion of vorticity out of the vortex is significant but appears to be independent of the value of the Reynolds number. At later times, the departure of the shed circulation from its large Reynolds number behaviour is significantly affected by diffusive loss of vorticity through the symmetry axis. A timescale is proposed that describes when the viscous loss through the axis becomes relevant. The simulations provide benchmark results to evaluate simpler separation models such as point vortex and vortex sheet models. A comparison with vortex sheet results is included. (paper)

  5. Effects of ethanol on plasma protein shedding in the human stomach

    International Nuclear Information System (INIS)

    Brassinne, A.

    1979-01-01

    Plasma protein shedding in the stomach was measured in 23 normal individuals before and after intragastric administration of a 30% solution of ethyl alcohol. Two different methods were used to assess plasma protein shedding. The first technique utilizes [ 131 I] albumin and requires neutralization of the gastric juice. It was used in 12 subjects and failed to demonstrate any increase of plasma protein shedding under the influence of ethanol. The second technique which utilizes [ 51 Cr] chloride was used in 11 subjects. It demonstrated a significant increase of the gastric clearance of plasma protein which reached 2.5 times the control values. The [ 51 Cr] chloride technique does not require prior neutralization of gastric acidity. It is concluded that, in normal man, ethanol administration increases plasma protein shedding in the stomach when it is given in the presence of an acid gastric juice. The effect is not observed when the gastric acidity is neutralized

  6. Experimental Investigation of Vortex Shedding in High Reynolds Number Flow Over Compressor Blades in Cascade

    National Research Council Canada - National Science Library

    Lim, Choon

    2003-01-01

    .... Vortex shedding was determined to be a leading edge phenomenon as periodic shedding was only detected on the pressure side of the wake, The relationship between vortex shedding frequency and Reynolds...

  7. Community-based Men's Sheds: promoting male health, wellbeing and social inclusion in an international context.

    Science.gov (United States)

    Cordier, Reinie; Wilson, Nathan J

    2014-09-01

    Males experience greater mortality and morbidity than females in most Western countries. The Australian and Irish National Male Health Policies aim to develop a framework to address this gendered health disparity. Men's Sheds have a distinct community development philosophy and are thus identified in both policies as an ideal location to address social isolation and positively impact the health and wellbeing of males who attend. The aim of this international cross-sectional survey was to gather information about Men's Sheds, the people who attend Men's Sheds, the activities at Men's Sheds, and the social and health dimensions of Men's Sheds. Results demonstrate that Men's Sheds are contributing a dual health and social role for a range of male subgroups. In particular, Men's Sheds have an outward social focus, supporting the social and mental health needs of men; health promotion and health literacy are key features of Men's Sheds. Men's Sheds have an important role to play in addressing the gendered health disparity that males face. They serve as an exemplar to health promotion professionals of a community development context where the aims of male health policy can be actualized as one part of a wider suite of global initiatives to reduce the gendered health disparity. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.

    Science.gov (United States)

    Phipps, Warren; Saracino, Misty; Magaret, Amalia; Selke, Stacy; Remington, Mike; Huang, Meei-Li; Warren, Terri; Casper, Corey; Corey, Lawrence; Wald, Anna

    2011-01-15

    Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking. For this study, 377 healthy adults with history of symptomatic genital HSV-2 infection collected anogenital swabs for HSV-2 DNA polymerase chain reaction for at least 30 consecutive days. Time since first genital herpes episode was significantly associated with reduced genital shedding. Total HSV shedding occurred on 33.6% of days in participants <1 year, 20.6% in those 1-9 years, and 16.7% in those ≥10 years from first episode. Subclinical HSV shedding occurred on 26.2% of days among participants <1 year, 13.1% in those 1-9 years, and 9.3% in those ≥10 years from first episode. On days with HSV detection, mean quantity was 4.9 log₁₀ copies/mL for those <1 year, 4.7 log₁₀ copies/mL among those 1-9 years, and 4.6 log₁₀ copies/mL among those ≥10 years since first episode. Rates of total and subclinical HSV-2 shedding decrease after the first year following the initial clinical episode. However, viral shedding persists at high rates and copy numbers years after infection, and therefore may pose continued risk of HSV-2 transmission to sexual partners.

  9. Virus and host-specific differences in oral human herpesvirus shedding kinetics among Ugandan women and children.

    Science.gov (United States)

    Matrajt, Laura; Gantt, Soren; Mayer, Bryan T; Krantz, Elizabeth M; Orem, Jackson; Wald, Anna; Corey, Lawrence; Schiffer, Joshua T; Casper, Corey

    2017-10-12

    Human herpesviruses (HHV) establish lifelong latent infection and are transmitted primarily via shedding at mucosal surfaces. Each HHV causes a unique spectrum of disease depending on the infected individual's age and immunity. We collected weekly oral swabs from young children and mothers in 32 Ugandan households for a median of one year. We characterized kinetics of oral shedding during primary and chronic infection for each virus. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and HHV-6 were shed at high rates following primary infection. The rate of oral herpes simplex virus (HSV) shedding was lower overall, and children and mothers with chronic HSV infection had lower shedding rates than children with primary infection. CMV shedding rate and viral load were higher in children with primary infection compared to children with chronic infection, and even lower in mothers with chronic infection. HHV-6 shedding rate and viral load were similar between children with primary or chronic infection, but lower in mothers. EBV shedding rate and quantity decreased less dramatically in mothers versus children, with HIV-positive mothers shedding at a higher rate than HIV-negative mothers. Each HHV has a distinct pattern of oral shedding which depends partially on the age and immune status of the host.

  10. A Bankruptcy Problem Approach to Load-shedding in Multiagent-based Microgrid Operation

    Directory of Open Access Journals (Sweden)

    Yujin Lim

    2010-09-01

    Full Text Available A microgrid is composed of distributed power generation systems (DGs, distributed energy storage devices (DSs, and loads. To maintain a specific frequency in the islanded mode as an important requirement,  the control of DGs’ output and charge action of DSs are used in supply surplus conditions and load-shedding and discharge action of DSs are used in supply shortage conditions. Recently, multiagent systems for autonomous microgrid operation have been studied. Especially, load-shedding, which is intentional reduction of electricity use, is a critical problem in islanded microgrid operation based on the multiagent system. Therefore, effective schemes for load-shedding are required. Meanwhile, the bankruptcy problem deals with dividing short resources among multiple agents. In order to solve the bankruptcy problem, division rules, such as the constrained equal awards rule (CEA, the constrained equal losses rule (CEL, and the random arrival rule (RA, have been used. In this paper, we approach load-shedding as a bankruptcy problem. We compare load-shedding results by above-mentioned rules in islanded microgrid operation based on wireless sensor network (WSN as the communication link for an agent’s interactions.

  11. Under-Frequency Load Shedding Technique Considering Event-Based for an Islanded Distribution Network

    Directory of Open Access Journals (Sweden)

    Hasmaini Mohamad

    2016-06-01

    Full Text Available One of the biggest challenge for an islanding operation is to sustain the frequency stability. A large power imbalance following islanding would cause under-frequency, hence an appropriate control is required to shed certain amount of load. The main objective of this research is to develop an adaptive under-frequency load shedding (UFLS technique for an islanding system. The technique is designed considering an event-based which includes the moment system is islanded and a tripping of any DG unit during islanding operation. A disturbance magnitude is calculated to determine the amount of load to be shed. The technique is modeled by using PSCAD simulation tool. A simulation studies on a distribution network with mini hydro generation is carried out to evaluate the UFLS model. It is performed under different load condition: peak and base load. Results show that the load shedding technique have successfully shed certain amount of load and stabilized the system frequency.

  12. Wake shed by an accelerating carangiform fish

    Science.gov (United States)

    Ting, Shang-Chieh; Yang, Jing-Tang

    2008-11-01

    We reveal an important fact that momentum change observed in the wake of an accelerating carangiform fish does not necessarily elucidate orientations of propulsive forces produced. An accelerating Crucian Carp (Carassius auratus) was found to shed a wake with net forward fluid momentum, which seemed drag-producing. Based on Newton's law, however, an accelerating fish is expected to shed a thrust wake with net rearward fluid momentum, rather than a drag wake. The unusual wake pattern observed is considered to be resulted primarily from the effect of pressure gradient created by accelerating movements of the fish. Ambient fluids tend to be sucked into low pressure zones behind an accelerating fish, resulting in forward orientations of jets recognizable in the wake. Accordingly, as to an accelerating fish, identifying force orientations from the wake requires considering also the effect of pressure gradient.

  13. Reduction of Salmonella Shedding by Sows during Gestation in Relation to Its Fecal Microbiome

    Directory of Open Access Journals (Sweden)

    Guillaume Larivière-Gauthier

    2017-11-01

    Full Text Available Pork meat is estimated to be responsible for 10–20% of human salmonellosis cases in Europe. Control strategies at the farm could reduce contamination at the slaughterhouse. One of the targeted sectors of production is maternity, where sows could be Salmonella reservoirs. The aim of this study was to assess the dynamics of shedding of Salmonella in terms of variation in both shedding prevalence and strains excreted during gestation in Quebec’s maternity sector. The evolution of the fecal microbiota of these sows during gestation was also assessed to detect bacterial populations associated with these variations. A total of 73 sows both at the beginning and the end of the gestation were randomly selected and their fecal matter was analyzed. Salmonella detection was conducted using a method that includes two selective enrichment media (MSRV and TBG. Nine isolates per positive samples were collected. Among the 73 sows tested, 27 were shedding Salmonella. Sows in the first third of their gestation shed Salmonella significantly more frequently (21/27 than those in the last third (6/46 (χ2P < 0.05. The shedding status of 19 of the sows that were previously sampled in the first third of their gestation was followed, this time in the last third of their gestation, which confirmed reduction of shedding. Using 16S rRNA gene sequencing and qPCR, significant differences between the fecal flora of sows at the beginning and the end of the gestation, shedding Salmonella or not and with different parity number were detected. Using MaAsLin, multiple OTUs were found to be associated with the time of gestation, the status of Salmonella excretion and parity number. Some of the identified taxa could be linked to the reduction of the shedding of Salmonella at the end of gestation. In this study, we showed that the level of Salmonella shedding was variable during gestation with significantly higher shedding at the beginning rather than at the end of gestation. We

  14. Zika Virus Shedding in Semen of Symptomatic Infected Men.

    Science.gov (United States)

    Mead, Paul S; Duggal, Nisha K; Hook, Sarah A; Delorey, Mark; Fischer, Marc; Olzenak McGuire, Dana; Becksted, Heidi; Max, Ryan J; Anishchenko, Michael; Schwartz, Amy M; Tzeng, Wen-Pin; Nelson, Christina A; McDonald, Erin M; Brooks, John T; Brault, Aaron C; Hinckley, Alison F

    2018-04-12

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has been linked to adverse birth outcomes. Previous reports have shown that person-to-person transmission can occur by means of sexual contact. We conducted a prospective study involving men with symptomatic ZIKV infection to determine the frequency and duration of ZIKV shedding in semen and urine and to identify risk factors for prolonged shedding in these fluids. Specimens were obtained twice per month for 6 months after illness onset and were tested by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for ZIKV RNA and by Vero cell culture and plaque assay for infectious ZIKV. A total of 1327 semen samples from 184 men and 1038 urine samples from 183 men were obtained 14 to 304 days after illness onset. ZIKV RNA was detected in the urine of 7 men (4%) and in the semen of 60 (33%), including in semen samples from 22 of 36 men (61%) who were tested within 30 days after illness onset. ZIKV RNA shedding in semen decreased substantially during the 3 months after illness onset but continued for 281 days in 1 man (1%). Factors that were independently associated with prolonged RNA shedding included older age, less frequent ejaculation, and the presence of certain symptoms at the time of initial illness. Infectious ZIKV was isolated from 3 of 78 semen samples with detectable ZIKV RNA, all obtained within 30 days after illness onset and all with at least 7.0 log 10 ZIKV RNA copies per milliliter of semen. ZIKV RNA was commonly present in the semen of men with symptomatic ZIKV infection and persisted in some men for more than 6 months. In contrast, shedding of infectious ZIKV appeared to be much less common and was limited to the first few weeks after illness onset. (Funded by the Centers for Disease Control and Prevention.).

  15. Hot-Wire Calibration at Low Velocities: Revisiting the Vortex Shedding Method

    Directory of Open Access Journals (Sweden)

    Sohrab S. Sattarzadeh

    2013-01-01

    Full Text Available The necessity to calibrate hot-wire probes against a known velocity causes problems at low velocities, due to the inherent inaccuracy of pressure transducers at low differential pressures. The vortex shedding calibration method is in this respect a recommended technique to obtain calibration data at low velocities, due to its simplicity and accuracy. However, it has mainly been applied in a low and narrow Reynolds number range known as the laminar vortex shedding regime. Here, on the other hand, we propose to utilize the irregular vortex shedding regime and show where the probe needs to be placed with respect to the cylinder in order to obtain unambiguous calibration data.

  16. Birds shed RNA-viruses according to the pareto principle.

    Directory of Open Access Journals (Sweden)

    Mark D Jankowski

    Full Text Available A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian - pathogen (RNA-virus studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality was 0.687 (0.036 SEM, and that 22.0% (0.90 SEM of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics.

  17. Birds shed RNA-viruses according to the pareto principle.

    Science.gov (United States)

    Jankowski, Mark D; Williams, Christopher J; Fair, Jeanne M; Owen, Jennifer C

    2013-01-01

    A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian) - pathogen (RNA-virus) studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality) was 0.687 (0.036 SEM), and that 22.0% (0.90 SEM) of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics.

  18. Tubular kidney injury molecule-1 in protein-overload nephropathy

    NARCIS (Netherlands)

    van Timmeren, Mirjan M.; Bakker, Stephan J. L.; Vaidya, Vishal S.; Bailly, Veronique; Schuurs, Theo A.; Damman, Jeffrey; Stegeman, Coen A.; Bonventre, Joseph V.; van Goor, Harry

    Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and

  19. Faecal Campylobacter shedding among dogs in animal shelters across Texas.

    Science.gov (United States)

    Leahy, A M; Cummings, K J; Rodriguez-Rivera, L D; Hamer, S A; Lawhon, S D

    2017-12-01

    Epidemiologic studies on faecal Campylobacter shedding among dogs in the United States have been limited, despite evidence that the incidence of human campylobacteriosis has increased over the last decade. Our objectives were to estimate the prevalence of faecal Campylobacter shedding among shelter dogs in Texas, to estimate the specific prevalence of Campylobacter jejuni and Campylobacter coli shedding, and to identify risk factors for Campylobacter-positive status. Using a cross-sectional study design, we collected faecal samples from dogs in six animal shelters across Texas between May and December, 2014. Quantitative PCR protocols were used to detect Campylobacter in samples and to specifically identify C. jejuni and C. coli. The prevalence of faecal Campylobacter shedding among sampled dogs was 75.7% (140/185). Prevalence varied significantly by shelter (p = .03), ranging from 57% to 93%. There was a marginal association (p = .06) between abnormal faecal consistency and positive Campylobacter status, after controlling for shelter as a random effect. However, approximately 70% of Campylobacter-positive dogs had grossly normal faeces. Campylobacter prevalence did not vary significantly by age group or sex. The prevalence of C. jejuni-positive samples was 5.4% (10/185), but C. coli was not detected in any samples. Dogs are a potential source of zoonotic Campylobacter transmission. © 2017 Blackwell Verlag GmbH.

  20. Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs.

    Science.gov (United States)

    Kobinger, Gary P; Leung, Anders; Neufeld, James; Richardson, Jason S; Falzarano, Darryl; Smith, Greg; Tierney, Kevin; Patel, Ami; Weingartl, Hana M

    2011-07-15

    (See the editorial commentary by Bausch, on pages 179-81.) Reston ebolavirus was recently detected in pigs in the Philippines. Specific antibodies were found in pig farmers, indicating exposure to the virus. This important observation raises the possibility that pigs may be susceptible to Ebola virus infection, including from other species, such as Zaire ebolavirus (ZEBOV), and can transmit to other susceptible hosts. This study investigated whether ZEBOV, a species commonly reemerging in central Africa, can replicate and induce disease in pigs and can be transmitted to naive animals. Domesticated Landrace pigs were challenged through mucosal exposure with a total of 1 ×10(6) plaque-forming units of ZEBOV and monitored for virus replication, shedding, and pathogenesis. Using similar conditions, virus transmission from infected to naive animals was evaluated in a second set of pigs. Following mucosal exposure, pigs replicated ZEBOV to high titers (reaching 10(7) median tissue culture infective doses/mL), mainly in the respiratory tract, and developed severe lung pathology. Shedding from the oronasal mucosa was detected for up to 14 days after infection, and transmission was confirmed in all naive pigs cohabiting with inoculated animals. These results shed light on the susceptibility of pigs to ZEBOV infection and identify an unexpected site of virus amplification and shedding linked to transmission of infectious virus.

  1. Reinfusion of Shed Blood Following Pediatric Orthopaedic Surgery

    National Research Council Canada - National Science Library

    Blevins, Field

    1991-01-01

    .... The use of a system for salvage and reinfusion of nonwashed shed blood postoperatively is recommended as a safe method to minimize the need for homologous transfusion, especially when there is...

  2. Hjemløshed i Danmark 2011

    DEFF Research Database (Denmark)

    Lauritzen, Heidi Hesselberg; Boje-Kovacs, Bence; Benjaminsen, Lars

    Rapporten fremlægger resultaterne af den tredje nationale kortlægning af hjemløshed i Danmark og giver et ajourført billede af omfanget og karakteren af hjemløsheden. Ligesom i de to forrige optællinger blev der i kortlægningsugen (uge 6) registreret ca. 5.000 hjemløse. Sammensætningen af gruppen...

  3. Particle shedding from peristaltic pump tubing in biopharmaceutical drug product manufacturing.

    Science.gov (United States)

    Saller, Verena; Matilainen, Julia; Grauschopf, Ulla; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

    2015-04-01

    In a typical manufacturing setup for biopharmaceutical drug products, the fill and dosing pump is placed after the final sterile filtration unit in order to ensure adequate dispensing accuracy and avoid backpressure peaks. Given the sensitivity of protein molecules, peristaltic pumps are often preferred over piston pumps. However, particles may be shed from the silicone tubing employed. In this study, particle shedding and a potential turbidity increase during peristaltic pumping of water and buffer were investigated using three types of commercially available silicone tubing. In the recirculates, mainly particles of around 200 nm next to a very small fraction of particles in the lower micrometer range were found. Using 3D laser scanning microscopy, surface roughness of the inner tubing surface was found to be a determining factor for particle shedding from silicone tubing. As the propensity toward particle shedding varied between tubing types and also cannot be concluded from manufacturer's specifications, individual testing with the presented methods is recommended during tubing qualification. Choosing low abrasive tubing can help to further minimize the very low particle counts to be expected in pharmaceutical drug products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Wind Forced Variability in Eddy Formation, Eddy Shedding, and the Separation of the East Australian Current

    Science.gov (United States)

    Bull, Christopher Y. S.; Kiss, Andrew E.; Jourdain, Nicolas C.; England, Matthew H.; van Sebille, Erik

    2017-12-01

    The East Australian Current (EAC), like many other subtropical western boundary currents, is believed to be penetrating further poleward in recent decades. Previous observational and model studies have used steady state dynamics to relate changes in the westerly winds to changes in the separation behavior of the EAC. As yet, little work has been undertaken on the impact of forcing variability on the EAC and Tasman Sea circulation. Here using an eddy-permitting regional ocean model, we present a suite of simulations forced by the same time-mean fields, but with different atmospheric and remote ocean variability. These eddy-permitting results demonstrate the nonlinear response of the EAC to variable, nonstationary inhomogeneous forcing. These simulations show an EAC with high intrinsic variability and stochastic eddy shedding. We show that wind stress variability on time scales shorter than 56 days leads to increases in eddy shedding rates and southward eddy propagation, producing an increased transport and southward reach of the mean EAC extension. We adopt an energetics framework that shows the EAC extension changes to be coincident with an increase in offshore, upstream eddy variance (via increased barotropic instability) and increase in subsurface mean kinetic energy along the length of the EAC. The response of EAC separation to regional variable wind stress has important implications for both past and future climate change studies.

  5. Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Griffins O Manguro

    Full Text Available Genital ulcer disease (GUD prevalence increases in the first month of antiretroviral treatment (ART, followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2, we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation.We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment.At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period.Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation.

  6. CAD Instructor Designs Eco-Friendly Shed

    Science.gov (United States)

    Schwendau, Mark

    2013-01-01

    Dissatisfied with the options offered by big box stores--and wanting to save some money and go as green as possible--the author puts his design and construction skills to good use. In this article, he shares how he designed and built an eco-friendly shed. He says he is very pleased with the results of working with his own design, reducing waste,…

  7. [Blood conservation effect and safety of shed mediastinal blood autotransfusion after cardiac surgery].

    Science.gov (United States)

    Komiya, T; Ban, K; Yamazaki, K; Date, O; Nakamura, T; Kanzaki, Y

    1998-10-01

    Autotransfusion of shed mediastinal blood after cardiac surgery has been used to reduce risks related to homologous blood transfusions. To document the efficacy and safety of autotransfusion, we compared clinical findings of 80 patients receiving shed mediastinal blood (autotransfusion group) with those of the control group of 52 patients. The amount of the autotransfusion was limited to 800 ml, given the potentially harmful effects of shed blood transfusion. The mean transfused shed volume was 314 +/- 236 ml (S.D.). The serum levels of FDP-E, D-dimer and TAT after autotransfusion were higher in the autotransfusion group than in the control group (p = 0.01, p = 0.0004, p = 0.001, respectively). However, postoperative blood loss and the rate of reexploration for bleeding were similar in the two groups. The patients receiving blood products were fewer in the autotransfusion group than those in the control group (21% vs 44%; p = 0.005). Autotransfusion did not increase postoperative complications, including infection. Thus, although autotransfusion of mediastinal shed blood has the potential to affect hemostasis, unless the amount of autotransfusion exceeds 800 ml, it appears that this method is clinically safe and effective as a mean of blood conservation.

  8. Effect of antigen shedding on targeted delivery of immunotoxins in solid tumors from a mathematical model.

    Directory of Open Access Journals (Sweden)

    Youngshang Pak

    Full Text Available Most cancer-specific antigens used as targets of antibody-drug conjugates and immunotoxins are shed from the cell surface (Zhang & Pastan (2008 Clin. Cancer Res. 14: 7981-7986, although at widely varying rates and by different mechanisms (Dello Sbarba & Rovida (2002 Biol. Chem. 383: 69-83. Why many cancer-specific antigens are shed and how the shedding affects delivery efficiency of antibody-based protein drugs are poorly understood questions at present. Before a detailed numerical study, it was assumed that antigen shedding would reduce the efficacy of antibody-drug conjugates and immunotoxins. However, our previous study using a comprehensive mathematical model showed that antigen shedding can significantly improve the efficacy of the mesothelin-binding immunotoxin, SS1P (anti-mesothelin-Fv-PE38, and suggested that receptor shedding can be a general mechanism for enhancing the effect of inter-cellular signaling molecules. Here, we improved this model and applied it to both SS1P and another recombinant immunotoxin, LMB-2, which targets CD25. We show that the effect of antigen shedding is influenced by a number of factors including the number of antigen molecules on the cell surface and the endocytosis rate. The high shedding rate of mesothelin is beneficial for SS1P, for which the antigen is large in number and endocytosed rapidly. On the other hand, the slow shedding of CD25 is beneficial for LMB-2, for which the antigen is small in number and endocytosed slowly.

  9. Quantifying shedding of synthetic fibers from textiles; a source of microplastics released into the environment.

    Science.gov (United States)

    Carney Almroth, Bethanie M; Åström, Linn; Roslund, Sofia; Petersson, Hanna; Johansson, Mats; Persson, Nils-Krister

    2018-01-01

    Microplastics in the environment are a subject of intense research as they pose a potential threat to marine organisms. Plastic fibers from textiles have been indicated as a major source of this type of contaminant, entering the oceans via wastewater and diverse non-point sources. Their presence is also documented in terrestrial samples. In this study, the amount of microfibers shedding from synthetic textiles was measured for three materials (acrylic, nylon, polyester), knit using different gauges and techniques. All textiles were found to shed, but polyester fleece fabrics shed the greatest amounts, averaging 7360 fibers/m -2 /L -1 in one wash, compared with polyester fabrics which shed 87 fibers/m -2 /L -1 . We found that loose textile constructions shed more, as did worn fabrics, and high twist yarns are to be preferred for shed reduction. Since fiber from clothing is a potentially important source of microplastics, we suggest that smarter textile construction, prewashing and vacuum exhaustion at production sites, and use of more efficient filters in household washing machines could help mitigate this problem.

  10. Prolonged Shedding of Human Parechovirus in Feces of Young Children after Symptomatic Infection

    NARCIS (Netherlands)

    Wildenbeest, Joanne G; Benschop, Kimberley S M; Bouma-de Jongh, Saskia; Wolthers, Katja C; Pajkrt, Dasja

    2016-01-01

    After symptomatic human parechovirus (HPeV) infection in infants, the duration of (mostly asymptomatic) shedding in feces was 2-24 weeks (median 58 days). HPeV cycle threshold value could neither differentiate between symptomatic disease and asymptomatic shedding nor between severe and mild disease

  11. Reliability Constrained Priority Load Shedding for Aerospace Power System Automation

    Science.gov (United States)

    Momoh, James A.; Zhu, Jizhong; Kaddah, Sahar S.; Dolce, James L. (Technical Monitor)

    2000-01-01

    The need for improving load shedding on board the space station is one of the goals of aerospace power system automation. To accelerate the optimum load-shedding functions, several constraints must be involved. These constraints include congestion margin determined by weighted probability contingency, component/system reliability index, generation rescheduling. The impact of different faults and indices for computing reliability were defined before optimization. The optimum load schedule is done based on priority, value and location of loads. An optimization strategy capable of handling discrete decision making, such as Everett optimization, is proposed. We extended Everett method to handle expected congestion margin and reliability index as constraints. To make it effective for real time load dispatch process, a rule-based scheme is presented in the optimization method. It assists in selecting which feeder load to be shed, the location of the load, the value, priority of the load and cost benefit analysis of the load profile is included in the scheme. The scheme is tested using a benchmark NASA system consisting of generators, loads and network.

  12. Velocity measurement by vortex shedding. Contribution to the mass-flow measurement

    International Nuclear Information System (INIS)

    Martinez Piquer, T.

    1988-01-01

    The phenomenon of vortex shedding has been known for centuries and has been the subject of scientific studies for about one hundred years. It is only in the ten last years that is has been applied to the measurement of fluids velocity. In 1878 F. Strouhal observed the vortex shedding phenomenon and shown that the shedding frequency of a wire vibrating in the wind was related to the wire diameter and the wind velocity. Rayleigh, who introduced the non-dimensional Strouhal number, von Karman and Rohsko, carried out extensive work or the subject which indicated that vortex shedding could form the basis for a new type of flowmeter. The thesis describes two parallel lines of investigation which study in depth the practical applications of vortex shedding. The first one deals with the measure of velocity and it presents the novelty of a bluff body with a cross-section which has not been used until this day. This body is a circular cylinder with a two-dimensional slit along the diameter and situated in crossdirection to the fluid's stream. It possesses excellent characteristics and it is the most stable as a vortex shedder, which gives it great advantage to the rest of the shapes used until now. The detection of the vortex has been performed by measuring the pressure changes generated by the vortex on two posts situated just beside the slit. To calculate the frequency of the vortex shedding, we obtain the difference of the mentioned signals, which are the same and 180 out of phase. Finding out the period of the autocorrelation function of this signal we can estimate the velocity of the fluid. A logical equipment based on a microprocessor has been designed for the calculation using a zero-crossing time algorithm implemented in assembler language. The second line of research refers to a new method of measure mass flow. The pressure signal generated by the vortex has an intensity which is proportional to the density and to the square of the velocity. Since we have already

  13. Fuzzy Load-Shedding Strategy Considering Photovoltaic Output Fluctuation Characteristics and Static Voltage Stability

    Directory of Open Access Journals (Sweden)

    Sheng Li

    2018-03-01

    Full Text Available Based on the equilibrium point equations of a classic three-node system integrated with a large-scale photovoltaic cell (PV power plant, the impact of PV output fluctuation on the saddle-node bifurcation (SNB was derived and analyzed. When PV runs in a unity power factor and the PV output active power Ppv is not too large (several hundred MW and below, the PV output fluctuation has little effect on the SNB point position and load margin index, so that the load margin index can be calculated online using the SNB point at Ppv = 0 pu. On the other hand, the local reactive power compensation in the load center can effectively raise the load bus voltage and make the voltage stability problem become more concealed; the traditional under-voltage load-shedding (UVLS strategy only carries out load shedding when the bus voltage amplitude is below the specified value and cannot effectively maintain the system static voltage stability in some occasions. In this paper, a fuzzy load-shedding strategy considering the impact of PV output fluctuations for the large-scale PV grid-connected system was designed, taking the load bus voltage amplitude and load margin index as fuzzy input variables, and the load-shedding command as a fuzzy output variable. Nine fuzzy IF-THEN rules were extracted for the fuzzy controller and the corresponding practical calculation method of load-shedding quantity was put forward. The simulation results of the classic three-node system and IEEE 14-bus system, both with a 100 MW PV power plant, verified the effectiveness of the fuzzy load-shedding controller whose input variable load margin index was calculated using the SNB point when the PV active power output was 0. The designed fuzzy load-shedding strategy can compensate for the defect—that the traditional UVLS strategy cannot effectively guarantee the system static voltage stability—and it can be widely used in power grids integrated with PV power plants whose scales are at a

  14. Strongyle egg shedding consistency in horses on farms using selective therapy in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Martin Krarup; Haaning, Niels; Olsen, Susanne Nautrup

    2006-01-01

    Knowledge of horses that shed the same number of strongyle eggs over time can lead to the optimization of parasite control strategies. This study evaluated shedding of strongyle eggs in 424 horses on 10 farms whan a selective anthelmintic treatment regime was used over a 3-year period....

  15. INTERNAL STRUCTURE OF ASTEROIDS HAVING SURFACE SHEDDING DUE TO ROTATIONAL INSTABILITY

    Energy Technology Data Exchange (ETDEWEB)

    Hirabayashi, Masatoshi [Research Associate, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States); Sánchez, Diego Paul [Senior Research Associate, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States); Scheeres, Daniel J., E-mail: masatoshi.hirabayashi@colorado.edu [Richard Seebass Chair, Professor, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States)

    2015-07-20

    Surface shedding of an asteroid is a failure mode where surface materials fly off due to strong centrifugal forces beyond the critical spin period, while the internal structure does not deform significantly. This paper proposes a possible structure of an asteroid interior that leads to surface shedding due to rapid rotation rates. A rubble pile asteroid is modeled as a spheroid composed of a surface shell and a concentric internal core, the entire assembly called the test body. The test body is assumed to be uniformly rotating around a constant rotation axis. We also assume that while the bulk density and the friction angle are constant, the cohesion of the surface shell is different from that of the internal core. First, developing an analytical model based on limit analysis, we provide the upper and lower bounds for the actual surface shedding condition. Second, we use a Soft-sphere Discrete Element Method (SSDEM) to study dynamical deformation of the test body due to a quasi-static spin-up. In this paper we show the consistency of both approaches. Additionally, the SSDEM simulations show that the initial failure always occurs locally and not globally. In addition, as the core becomes larger, the size of lofted components becomes smaller. These results imply that if there is a strong core in a progenitor body, surface shedding is the most likely failure mode.

  16. INTERNAL STRUCTURE OF ASTEROIDS HAVING SURFACE SHEDDING DUE TO ROTATIONAL INSTABILITY

    International Nuclear Information System (INIS)

    Hirabayashi, Masatoshi; Sánchez, Diego Paul; Scheeres, Daniel J.

    2015-01-01

    Surface shedding of an asteroid is a failure mode where surface materials fly off due to strong centrifugal forces beyond the critical spin period, while the internal structure does not deform significantly. This paper proposes a possible structure of an asteroid interior that leads to surface shedding due to rapid rotation rates. A rubble pile asteroid is modeled as a spheroid composed of a surface shell and a concentric internal core, the entire assembly called the test body. The test body is assumed to be uniformly rotating around a constant rotation axis. We also assume that while the bulk density and the friction angle are constant, the cohesion of the surface shell is different from that of the internal core. First, developing an analytical model based on limit analysis, we provide the upper and lower bounds for the actual surface shedding condition. Second, we use a Soft-sphere Discrete Element Method (SSDEM) to study dynamical deformation of the test body due to a quasi-static spin-up. In this paper we show the consistency of both approaches. Additionally, the SSDEM simulations show that the initial failure always occurs locally and not globally. In addition, as the core becomes larger, the size of lofted components becomes smaller. These results imply that if there is a strong core in a progenitor body, surface shedding is the most likely failure mode

  17. Men with disabilities - A cross sectional survey of health promotion, social inclusion and participation at community Men's Sheds.

    Science.gov (United States)

    Wilson, Nathan J; Cordier, Reinie; Parsons, Richard; Vaz, Sharmila; Buchanan, Angus

    2016-01-01

    The intersections between chronicity, disability and social inequality are well understood. Novel ways to counter the social determinants of health and disability are needed. Men's Sheds are a community space where men can participate in a range of shared activities and potentially experience a health and social benefits. This cross-sectional survey was conducted to inform future research by determining who attended Men's Sheds and the range of health, social, community, and educational activities undertaken there. This paper explores the membership of people with disabilities (PWD) at Men's Sheds and the factors that predict their membership. An online survey link was sent to all known Men's Sheds internationally in 2012. Data were analyzed using descriptive and inferential (univariate and multivariate) statistics. 32.2% of international sheds and 29% of Australian sheds specifically targeted the inclusion of PWD. 80% of these sheds have significantly more members with disabilities than sheds who do no target PWD. Factors associated with greater membership of PWD included the provision of transport, social outings and promoting occupational skills. PWD are being encouraged to join and are joining Men's Sheds. This is significant as the value of participation and inclusion toward better health and wellbeing is well known. Men's Sheds offer a community space where the social determinants of chronicity and disability can potentially be countered. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Influence of On-farm pig Salmonella status on Salmonella Shedding at Slaughter.

    Science.gov (United States)

    Casanova-Higes, A; Andrés-Barranco, S; Mainar-Jaime, R C

    2017-08-01

    The risk of Salmonella shedding among pigs at slaughter with regard to their previous on-farm Salmonella status was assessed in a group of pigs from a farm from NE of Spain. A total of 202 pigs that had been serologically monitored monthly during the fattening period and from which mesenteric lymph nodes (MLN) and faecal (SFEC) samples were collected at slaughter for Salmonella isolation were included. A repeated-measures anova was used to assess the relationship between mean OD% values during the fattening period and sampling time and bacteriology on MLN and SFEC. Pigs were also grouped into four groups, that is pigs seronegative during the fattening period and Salmonella negative in MLN (group A; n = 69); pigs seronegative during the fattening period but Salmonella positive in MLN (B; n = 36); pigs seropositive at least once and Salmonella positive in MLN (C; n = 50); and pigs seropositive at least once but Salmonella negative in (D; n = 47). Pigs shedding at slaughter seroconverted much earlier and showed much higher mean OD% values than non-shedders pigs. The proportion of Salmonella shedders in groups A and D was high and similar (26.1% and 29.8%, respectively), but significantly lower than that for groups B and C. The odds of shedding Salmonella for groups B and C were 4.8 (95% CI = 1.5-15.5) and 20.9 (3.7-118) times higher, respectively, when compared to A. It was concluded that a large proportion of Salmonella seronegative pigs may shed Salmonella at slaughter, which would be likely associated to previous exposure with contaminated environments (i.e. transport and lairage). For pigs already infected at farm, the likelihood of shedding Salmonella was much higher and may depend on whether the bacterium has colonized the MLN or not. The odds of shedding Salmonella spp. were always much higher for pigs in which Salmonella was isolated from MLN. © 2016 Blackwell Verlag GmbH.

  19. Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

    Science.gov (United States)

    Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

    2017-08-03

    The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

  20. Comparison of Coxiella burnetii shedding in milk of dairy bovine, caprine, and ovine herds.

    Science.gov (United States)

    Rodolakis, A; Berri, M; Héchard, C; Caudron, C; Souriau, A; Bodier, C C; Blanchard, B; Camuset, P; Devillechaise, P; Natorp, J C; Vadet, J P; Arricau-Bouvery, N

    2007-12-01

    The shedding of Coxiella burnetii in bovine, caprine, and ovine milk was measured using PCR, in 3 herds for each species, the bulk tank milk samples of which were positive at the time of their selection. Milk samples of 95 cows, 120 goats, and 90 ewes were sampled over 16 wk, as was the bulk tank milk. The shedding of C. burnetii in vaginal mucus and feces was checked at the beginning of the experiment and 2 mo later. The clinical signs in the selected herds as well as the duration and the shedding routes differed among the 3 species. The cows were asymptomatic and shed C. burnetii almost exclusively in milk. In one of the caprine herds, abortions due to C. burnetii were reported. The goats excreted the bacteria mainly in milk. In contrast, the ewes, which came from flocks with abortions due to Q fever (C. burnetii infection), shed the bacteria mostly in feces and in vaginal mucus. This could explain why human outbreaks of Q fever are more often related to ovine flocks than to bovine herds. These excretions did not seem more frequent when the samples were taken close to parturition. The samples were taken from 0 to 421 d after parturition in bovine herds and from 5 to 119 d and 11 to 238 d after parturition in the caprine and ovine herds, respectively. The shedding in milk was sometimes intermittent, and several animals shed the bacteria but were negative by ELISA: 80% of the ewes were seronegative, underscoring the lack of sensitivity of the ELISA tests available for veterinary diagnosis. The detection of antibodies in milk seems more sensitive than it is in serum.

  1. Neural net based determination of generator-shedding requirements in electric power systems

    Energy Technology Data Exchange (ETDEWEB)

    Djukanovic, M [Electrical Engineering Inst. ' Nikola Tesla' , Belgrade (Yugoslavia); Sobajic, D J; Pao, Y -H [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Electrical Engineering and Applied Physics Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Computer Engineering and Science AI WARE Inc., Cleveland, OH (United States)

    1992-09-01

    This paper presents an application of artificial neural networks (ANN) in support of a decision-making process by power system operators directed towards the fast stabilisation of multi-machine systems. The proposed approach considers generator shedding as the most effective discrete supplementary control for improving the dynamic performance of faulted power systems and preventing instabilities. The sensitivity of the transient energy function (TEF) with respect to changes in the amount of dropped generation is used during the training phase of ANNs to assess the critical amount of generator shedding required to prevent the loss of synchronism. The learning capabilities of neural nets are used to establish complex mappings between fault information and the amount of generation to be shed, suggesting it as the control signal to the power system operator. (author)

  2. Faecal shedding of antimicrobial-resistant Clostridium difficile strains by dogs.

    Science.gov (United States)

    Álvarez-Pérez, S; Blanco, J L; Peláez, T; Lanzarot, M P; Harmanus, C; Kuijper, E; García, M E

    2015-03-01

    To longitudinally assess the shedding of antimicrobial resistant Clostridium difficile strains by clinically healthy dogs raised at breeding facilities. 18 puppies from three different litters (#1, 2 and 3) were sampled weekly from parturition to day 20-55 postpartum. Faecal samples from the mothers of litters #2 and 3 were also available for analysis. Bacterial isolates were ribotyped, tested for in vitro antimicrobial susceptibility and further characterised. C. difficile was recovered from all sampled animals of litters #1 and 2, and a third of puppies from litter #3, but marked differences in C. difficile recovery were detected in different age groups (0-100%). Recovered PCR ribotypes included 056 (22 isolates), 010 (6 isolates), 078 and 213 (2 isolates each), and 009 and 020 (1 isolate each). Different ribotypes were shed by four individual animals. Regardless of their origin and ribotype, all isolates demonstrated full resistance to levofloxacin. Additionally, all but one isolate (belonging to ribotype 078) were resistant to ertapenem, and all ribotype 010 isolates displayed high-level resistance to clindamycin, clarithromycin and erythromycin. A single ribotype 078 isolate showed metronidazole heteroresistance. Healthy dogs can shed antimicrobial-resistant C. difficile strains. © 2014 British Small Animal Veterinary Association.

  3. Toxoplasma gondii: A study of oocyst re-shedding in domestic cats.

    Science.gov (United States)

    Zulpo, Dauton Luiz; Sammi, Ana Sue; Dos Santos, Joeleni Rosa; Sasse, João Pedro; Martins, Thais Agostinho; Minutti, Ana Flávia; Cardim, Sérgio Tosi; de Barros, Luiz Daniel; Navarro, Italmar Teodorico; Garcia, João Luis

    2018-01-15

    The aim of the present study was to evaluate the re-shedding of T. gondii oocysts in cats fed tissue cysts of homologous and heterologous strains 12, 24 and 36 months after the first infection. Thirteen cats were used in the present study and were divided into four groups: G1 (n=2), G2 (n=3), G3 (n=5), and G4 (n=3). G1, G3 and G4 cats were infected with brain cysts of ME49 and G2 with TgDoveBr8, both genotype II strains of T. gondii. The G1 and G2 cats were re-infected after twelve months with brain cysts of VEG strain (genotype III), and G3 cats were re-infected with TgDoveBr1 (genotype II). The G3 cats were re-infected a third time after 24 months from the second infection, and the G4 cats were re-infected 36 months after the initial infection with cysts of the VEG strain. The cats' feces were evaluated using fecal flotation and genotyped with PCR-RFLP. The serological responses for IgM, IgA and IgG were determined by ELISA. All cats shed oocysts after the initial infection. Only one G1 cat shed oocysts when re-infected after twelve months with the VEG strain. No G2 cats excreted oocysts after the second infection with VEG. G3 cats, when re-infected after twelve months with the TgDoveBr1 strain, did not shed oocysts. However, when challenged after a third time with the VEG strain, three out of four cats shed oocysts. In the G4 group, when re-infected after thirty-six months with the VEG strain, two out of three cats shed oocysts. All oocyst samples were genotyped and characterized as the same genotype from the inoculum. Protection against oocyst re-excretion occurred in 90%, 25%, and 33.4% of cats after 12, 24, and 36 months from the initial infection, respectively. Therefore, the environmental contamination by oocysts from re-infected adult cats is only 30% lower than from kittens. In conclusion, the excretion of T. gondii oocysts was higher in experimentally re-infected cats throughout the years, especially when a heterologous strain was used. Copyright © 2017

  4. Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ran; Xie, Jun; Wu, Han; Li, Guannan; Chen, Jianzhou; Chen, Qinhua; Wang, Lian; Xu, Biao, E-mail: xubiao@medmail.com.cn

    2016-05-20

    Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4 protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular

  5. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    Science.gov (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  6. Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission.

    Science.gov (United States)

    Oma, Veslemøy Sunniva; Tråvén, Madeleine; Alenius, Stefan; Myrmel, Mette; Stokstad, Maria

    2016-06-13

    Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. A live animal experiment was conducted, with direct contact between animal groups for 24 h as challenge procedure. Four naïve calves were commingled with a group of six naturally infected calves and sequentially euthanized. Two naïve sentinel calves were commingled with the experimentally exposed group three weeks after exposure. Nasal swabs, feces, blood and tissue samples were analyzed for viral RNA by RT-qPCR, and virus isolation was performed on nasal swabs. Serum was analyzed for BCoV antibodies. The calves showed mild general signs, and the most prominent signs were from the respiratory system. The overall clinical score corresponded well with the shedding of viral RNA the first three weeks after challenge. General depression and cough were the signs that correlated best with shedding of BCoV RNA, while peak respiratory rate and peak rectal temperature appeared more than a week later than the peak shedding. Nasal shedding preceded fecal shedding, and the calves had detectable amounts of viral RNA intermittently in feces through day 35 and in nasal secretions through day 28, however virus isolation was unsuccessful from day six and day 18 from the two calves investigated. Viral RNA was not detected in blood, but was found in lymphatic tissue through day 42 after challenge. Although the calves were shedding BCoV RNA 21 days after infection the sentinel animals were not infected

  7. Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells

    International Nuclear Information System (INIS)

    Wu Hualin; Lin ChiIou; Huang Yuanli; Chen, Pin-Shern; Kuo, Cheng-Hsiang; Chen, Mei-Shing; Wu, G.C.-C.; Shi, G.-Y.; Yang, H.-Y.; Lee Hsinyu

    2008-01-01

    Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation

  8. Flavobacterium psychrophilum, invasion into and shedding by rainbow trout Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Madetoja, J.; Nyman, P.; Wiklund, T.

    2000-01-01

    The infection route of Flavobacterium psychrophilum into rainbow trout Oncorhynchus mykiss was studied using bath and cohabitation challenges as well as oral challenge with live feed as a vector. Additionally, the number of bacterial cells shed by infected fish into the surrounding water...... is discussed as an important invasion route for F. psychrophilum into the fish. The shedding rate of F. psychrophiIlun by infected fish was associated with water temperature and the mortality of the infected fish. High numbers of F. psychrophilum cells were released into the water by dead rainbow trout during...

  9. Coxiella burnetii shedding routes and antibody response after outbreaks of Q fever-induced abortion in dairy goat herds.

    Science.gov (United States)

    Rousset, Elodie; Berri, Mustapha; Durand, Benoit; Dufour, Philippe; Prigent, Myriam; Delcroix, Thibault; Touratier, Anne; Rodolakis, Annie

    2009-01-01

    Q fever is a zoonosis caused by Coxiella burnetii, a bacterium largely carried by ruminants and shed into milk, vaginal mucus, and feces. The main potential hazard to humans and animals is due to shedding of bacteria that can then persist in the environment and be aerosolized. The purpose of this study was to evaluate shedding after an outbreak of Q fever abortion in goat herds and to assess the relationship with the occurrence of abortions and antibody responses. Aborting and nonaborting goats were monitored by PCR for C. burnetii shedding 15 and 30 days after the abortion episodes. PCR analysis of all samples showed that 70% (n = 50) of the aborting and 53% (n = 70) of the nonaborting goats were positive. C. burnetii was shed into vaginal mucus, feces, and milk of 44%, 21%, and 38%, respectively, of goats that aborted and 27%, 20%, and 31%, respectively, of goats that delivered normally. Statistical comparison of these shedding results did not reveal any difference between these two groups. PCR results obtained for the vaginal and fecal routes were concordant in 81% of cases, whereas those for milk correlated with only 49% of cases with either vaginal or fecal shedding status. Serological analysis, using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and complement fixation tests, showed that at least 24% of the seronegative goats shed bacteria. Positive vaginal and fecal shedding, unlike positive milk shedding, was observed more often in animals that were weakly positive or negative by ELISA or IFA. Two opposite shedding trends were thus apparent for the milk and vaginal-fecal routes. Moreover, this study showed that a nonnegligible proportion of seronegative animals that delivered normally could excrete C. burnetii.

  10. A Bankruptcy Problem Approach to Load-shedding in Multiagent-based Microgrid Operation

    OpenAIRE

    Kim, Hak-Man; Kinoshita, Tetsuo; Lim, Yujin; Kim, Tai-Hoon

    2010-01-01

    A microgrid is composed of distributed power generation systems (DGs), distributed energy storage devices (DSs), and loads. To maintain a specific frequency in the islanded mode as an important requirement,  the control of DGs’ output and charge action of DSs are used in supply surplus conditions and load-shedding and discharge action of DSs are used in supply shortage conditions. Recently, multiagent systems for autonomous microgrid operation have been studied. Especially, load-shedding, whi...

  11. Proteomic Analysis of Leptospira interrogans Shed in Urine of Chronically Infected Hosts▿

    OpenAIRE

    Monahan, Avril M.; Callanan, John J.; Nally, Jarlath E.

    2008-01-01

    Leptospirosis is a global zoonotic disease. The causative agent, pathogenic Leptospira species, survives in the renal tubules of chronically infected hosts, from where leptospires are shed via urine into the environment. Infection of new hosts can present as an array of acute and chronic disease processes reflecting variations in host-pathogen interactions. The present study was designed to reproduce the carrier phase of infection in Rattus norvegicus, thus facilitating shedding of leptospire...

  12. Co-occurrence of Trichomonas vaginalis and bacterial vaginosis and vaginal shedding of HIV-1 RNA.

    Science.gov (United States)

    Fastring, Danielle R; Amedee, Angela; Gatski, Megan; Clark, Rebecca A; Mena, Leandro A; Levison, Judy; Schmidt, Norine; Rice, Janet; Gustat, Jeanette; Kissinger, Patricia

    2014-03-01

    Trichomonas vaginalis (TV) and bacterial vaginosis (BV) are independently associated with increased risk of vaginal shedding in HIV-positive women. Because these 2 conditions commonly co-occur, this study was undertaken to examine the association between TV/BV co-occurrence and vaginal shedding of HIV-1 RNA. HIV-positive women attending outpatient HIV clinics in 3 urban US cities underwent a clinical examination; were screened for TV, BV, Neisseria gonorrhoeae, Chlamydia trachomatis, and vulvovaginal candidiasis; and completed a behavioral survey. Women shedding HIV-1 RNA vaginally (≥50 copies/mL) were compared with women who had an undetectable (women who were TV positive and BV positive or had co-occurrence of TV/BV had higher odds of shedding vaginally when compared with women who did not have these conditions. In this sample of 373 HIV-positive women, 43.1% (n = 161) had co-occurrence of TV/BV and 33.2% (n = 124) were shedding HIV-1 RNA vaginally. The odds of shedding HIV vaginally in the presence of TV alone or BV alone and when TV/BV co-occurred were 4.07 (95% confidence interval [CI], 1.78-9.37), 5.65 (95% CI, 2.64-12.01), and 18.63 (95% CI, 6.71-51.72), respectively, when compared with women with no diagnosis of TV or BV, and after adjusting for age, antiretroviral therapy status, and plasma viral load. T. vaginalis and BV were independently and synergistically related to vaginal shedding of HIV-1 RNA. Screening and prompt treatment of these 2 conditions among HIV-positive women are important not only clinically but for HIV prevention, as well.

  13. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    Science.gov (United States)

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Inhibition of TGF-β Signaling in SHED Enhances Endothelial Differentiation.

    Science.gov (United States)

    Xu, J G; Gong, T; Wang, Y Y; Zou, T; Heng, B C; Yang, Y Q; Zhang, C F

    2018-02-01

    Low efficiency of deriving endothelial cells (ECs) from adult stem cells hampers their utilization in tissue engineering studies. The purpose of this study was to investigate whether suppression of transforming growth factor beta (TGF-β) signaling could enhance the differentiation efficiency of dental pulp-derived stem cells into ECs. We initially used vascular endothelial growth factor A (VEGF-A) to stimulate 2 dental pulp-derived stem cells (dental pulp stem cells and stem cells from human exfoliated deciduous teeth [SHED]) and compared their differentiation capacity into ECs. We further evaluated whether the vascular endothelial growth factor receptor I (VEGF-RI)-specific ligand placental growth factor-1 (PlGF-1) could mediate endothelial differentiation. Finally, we investigated whether the TGF-β signaling inhibitor SB-431542 could enhance the inductive effect of VEGF-A on endothelial differentiation, as well as the underlying mechanisms involved. ECs differentiated from dental pulp-derived stem cells exhibited the typical phenotypes of primary ECs, with SHED possessing a higher endothelial differentiation potential than dental pulp stem cells. VEGFR1-specific ligand-PLGF exerted a negligible effect on SHED-ECs differentiation. Compared with VEGF-A alone, the combination of VEGF-A and SB-431542 significantly enhanced the endothelial differentiation of SHED. The presence of SB-431542 inhibited the phosphorylation of Suppressor of Mothers Against Decapentaplegic 2/3 (SMAD2/3), allowing for VEGF-A-dependent phosphorylation and upregulation of VEGFR2. Our results indicate that the combination of VEGF-A and SB-431542 could enhance the differentiation of dental pulp-derived stem cells into endothelial cells, and this process is mediated through enhancement of VEGF-A-VEGFR2 signaling and concomitant inhibition of TGF-β-SMAD2/3 signaling.

  15. Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes

    Directory of Open Access Journals (Sweden)

    Mark G. Martens

    2009-01-01

    Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P<.01, a 78% reduction. Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P<.01, a 78% reduction. However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P<.01. Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection.

  16. Shedding of a low pathogenic avian influenza virus in a common synanthropic mammal--the cottontail rabbit.

    Directory of Open Access Journals (Sweden)

    J Jeffrey Root

    Full Text Available BACKGROUND: Cottontails (Sylvilagus spp. are common mammals throughout much of the U.S. and are often found in peridomestic settings, potentially interacting with livestock and poultry operations. If these animals are susceptible to avian influenza virus (AIV infections and shed the virus in sufficient quantities they may pose a risk for movement of avian influenza viruses between wildlife and domestic animals in certain situations. METHODOLOGY/PRINCIPAL FINDINGS: To assess the viral shedding potential of AIV in cottontails, we nasally inoculated fourteen cottontails with a low pathogenic AIV (H4N6. All inoculated cottontails shed relatively large quantities of viral RNA both nasally (≤ 10(6.94 PCR EID50 equivalents/mL and orally (≤ 10(5.09 PCR EID50 equivalents/mL. However, oral shedding tended to decline more quickly than did nasal shedding. No animals showed any obvious signs of disease throughout the study. Evidence of a serological response was found in all infected rabbits at 22 days post infection in convalescent sera. CONCLUSIONS/SIGNIFICANCE: To our knowledge, cottontails have not been previously assessed for AIV shedding. However, it was obvious that they shed AIV RNA extensively via the nasal and oral routes. This is significant, as cottontails are widely distributed throughout the U.S. and elsewhere. These mammals are often found in highly peridomestic situations, such as farms, parks, and suburban neighborhoods, often becoming habituated to human activities. Thus, if infected these mammals could easily transport AIVs short distances.

  17. The shedding activity of ADAM17 is sequestered in lipid rafts

    International Nuclear Information System (INIS)

    Tellier, Edwige; Canault, Matthias; Rebsomen, Laure; Bonardo, Bernadette; Juhan-Vague, Irene; Nalbone, Gilles; Peiretti, Franck

    2006-01-01

    The tumor necrosis factor-alpha (TNF) converting enzyme (ADAM17) is a metalloprotease-disintegrin responsible for the cleavage of several biologically active transmembrane proteins. However, the substrate specificity of ADAM17 and the regulation of its shedding activity are still poorly understood. Here, we report that during its transport through the Golgi apparatus, ADAM17 is included in cholesterol-rich membrane microdomains (lipid rafts) where its prodomain is cleaved by furin. Consequently, ADAM17 shedding activity is sequestered in lipid rafts, which is confirmed by the fact that metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. Membrane cholesterol depletion increases the ADAM17-dependent shedding of these substrates demonstrating the importance of lipid rafts in the control of this process. Furthermore, ADAM17 substrates are present in different proportions in lipid rafts, suggesting that the entry of each of these substrates in these particular membrane microdomains is specifically regulated. Our data support the idea that one of the mechanisms regulating ADAM17 substrate cleavage involves protein partitioning in lipid rafts

  18. Shedding of Japanese Encephalitis Virus in Oral Fluid of Infected Swine.

    Science.gov (United States)

    Lyons, Amy C; Huang, Yan-Jang S; Park, So Lee; Ayers, Victoria B; Hettenbach, Susan M; Higgs, Stephen; McVey, D Scott; Noronha, Leela; Hsu, Wei-Wen; Vanlandingham, Dana L

    2018-05-09

    Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne flavivirus endemic in the Asia-Pacific region. Maintenance of JEV in nature involves enzootic transmission by competent Culex mosquitoes among susceptible avian and swine species. Historically, JEV has been regarded as one of the most important arthropod-borne viruses in Southeast Asia. Oronasal shedding of JEV from infected amplification hosts was not recognized until the recent discovery of vector-free transmission of JEV among domestic pigs. In this study, oral shedding of JEV was characterized in domestic pigs and miniature swine representing the feral phenotype. A rope-based sampling method followed by the detection of viral RNA using RT-qPCR allowed the collection and detection of JEV in oral fluid samples collected from intradermally challenged animals. The results suggest that the shedding of JEV in oral fluid can be readily detected by molecular diagnostic assays at the acute phase of infection. It also demonstrates the feasibility of this technique for the diagnosis and surveillance of JEV in swine species.

  19. Shedding of the immunodominant P20 surface antigen of Eimeria bovis sporozoites.

    OpenAIRE

    Speer, C A; Whitmire, W M

    1989-01-01

    P20 is an immunodominant surface antigen of Eimeria bovis sporozoites. As parasites underwent merogony within cultured bovine monocytes and Madin-Darby bovine kidney (MDBK) cells, P20 appeared to be shed gradually by meronts and was absent in type 1 and 2 first-generation merozoites. Meronts of E. bovis appeared to shed P20 into the parasitophorous vacuole of bovine monocytes, whereas MDBK cells evidently released P20 into the culture medium or destroyed its antigenic determinant.

  20. The Role of Shed PrPc in the Neuropathogenesis of HIV Infection.

    Science.gov (United States)

    Megra, Bezawit W; Eugenin, Eliseo A; Berman, Joan W

    2017-07-01

    HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP c ) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP c (sPrP c ) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP c from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, because treatment of astrocytes with rPrP c increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from rPrP c -treated astrocytes containing factors produced in response to this treatment, but not rPrP c by itself, cause increased chemotaxis of both uninfected and HIV-infected human monocytes, suggesting a role for sPrP c in monocyte recruitment into the brain. Furthermore, we examined whether PrP c participates in glutamate uptake and found that rPrP c decreased uptake of this metabolite in astrocytes, which could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrP c shedding and the effect of this sPrP c on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrP c could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. Vortex Shedding Characteristics of the Wake of a Thin Flat Plate with a Circular Trailing Edge

    Science.gov (United States)

    Rai, Man Mohan

    2018-01-01

    The near and very near wake of a thin flat plate with a circular trailing edge are investigated with direct numerical simulations (DNS). Data obtained for two different Reynolds numbers (based on plate thickness, D) are the main focus of this study. The separating boundary layers are turbulent in both cases. An earlier investigation of one of the cases (Case F) showed shed vortices in the wake that were about 1.0 D to 4.0 D in spanwise length. Considerable variation in both the strength and frequency of these shed vortices was observed. One objective of the present investigation is to determine the important contributors to this variability in strength and frequency of shed vortices and their finite spanwise extent. Analysis of the data shows that streamwise vortices in the separating boundary layer play an important role in strengthening/weakening of the shed vortices and that high/low-speed streaks in the boundary layer are important contributors to variability in shedding frequency. Both these features of the boundary layer contribute to the finite extent of the vortices in the spanwise direction. The second plate DNS (Case G, with 40 percent of the plate thickness of Case F) shows that while shedding intensity is weaker than obtained in Case F, many of the wake features are similar to that of Case F. This is important in understanding the path to the wake of the thin plate with a sharp trailing edge where shedding is absent. Here we also test the efficacy of a functional relationship between the shedding frequency and the Reynolds numbers based on the boundary layer momentum thickness (Re (sub theta) and D (Re (sub D)); data for developing this behavioral model is from Cases F & G and five earlier DNSs of the flat plate wake.

  2. Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma

    DEFF Research Database (Denmark)

    Etzerodt, Anders; Berg, Ronan M.G.; Plovsing, Ronni R.

    2017-01-01

    CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma â €soluble CD163' (sCD163) has become a biomarker for macroph......CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma â €soluble CD163' (sCD163) has become a biomarker...

  3. Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2

    Directory of Open Access Journals (Sweden)

    Wunner William

    2006-12-01

    Full Text Available Abstract Background Matrix protein 2 (M2 is an integral tetrameric membrane protein of influenza A virus (IAV. Its ectodomain (M2e shows remarkably little diversity amongst human IAV strains. As M2e-specific antibodies (Abs have been shown to reduce the severity of infection in animals, M2e is being studied for its capability of providing protection against a broad range of IAV strains. Presently, there is little information about the concentration of M2e-specific Abs in humans. Two previous studies made use of ELISA and Western blot against M2e peptides and recombinant M2 protein as immunosorbents, respectively, and reported Ab titers to be low or undetectable. An important caveat is that these assays may not have detected all Abs capable of binding to native tetrameric M2e. Therefore, we developed an assay likely to detect all M2e tetramer-specific Abs. Results We generated a HeLa cell line that expressed full length tetrameric M2 (HeLa-M2 or empty vector (HeLa-C10 under the control of the tetracycline response element. These cell lines were then used in parallel as immunosorbents in ELISA. The assay was standardized and M2e-specific Ab titers quantified by means of purified murine or chimeric (mouse variable regions, human constant regions M2e-specific Abs in the analysis of mouse and human sera, respectively. We found that the cell-based ELISA was substantially more effective than immobilized M2e peptide in detecting M2e-specific Abs in sera of mice that had recovered from repetitive IAV infections. Still, titers remained low ( Conclusion The results provide convincing evidence that M2e-specific Ab-mediated protection is currently lacking or suboptimal in humans.

  4. Vortex Shedding in the Wake Induced by a Real Elephant Seal Whisker

    Science.gov (United States)

    Turk, Jodi; Omilion, Alexis; Zhang, Wei; Kim, Jeong-Jae; Kim, Jeong-Ju; Choi, Woo-Rak; Lee, Sang-Joon

    2017-11-01

    Biomimicry has been adopted to create innovative solutions in a vast range of applications. One such application is the design of seal-whisker-inspired flow sensors for autonomous underwater vehicles (AUVs). In dark, cramped, and unstable terrain AUVs are not able to maneuver using visual and sonar-based navigation. Hence, it is critical to use underwater flow sensors to accurately detect minute disturbances in the surroundings. Certain seal whiskers exhibit a unique undulating three-dimensional morphology that can reduce vortex induced vibrations (VIVs) if the major axis of the whisker cross-section is aligned to the inflow. This allows the seal to precisely track prey fish upstream using solely their whiskers. The current study aims to understand the effect of a real seal whisker's morphology on the vortex shedding behavior. Despite extensive studies of wake induced by scaled whisker-like models, the vortex shedding in the wake of a real seal whisker is not well understood. A series of experiments are conducted with a high-speed Particle Imaging Velocimetry (PIV) system in a water channel to examine the vortex shedding downstream from a smooth whisker and an undulating whisker at a Reynolds number of a few hundred. Results of the vortex shedding induced by real seal whiskers can provide insights on developing high-sensitivity underwater flow sensors for AUVs and other whisker-inspired structures.

  5. Evaluation of the shedding of Sarcocystis falcatula sporocysts in experimentally infected Virginia opossums (Didelphis virginiana).

    Science.gov (United States)

    Porter, R A; Ginn, P E; Dame, J B; Greiner, E C

    2001-02-26

    Five Virginia opossums (Didelphis virginiana) were fed muscles of brown-headed cowbirds (Molothrus ater) containing sarcocysts of Sarcocystis falcatula. Shedding of sporocysts was confirmed in all five opossums by fecal flotation. Counts were conducted daily for 2 weeks and then biweekly until the animals were euthanized and necropsied. The average prepatent period was 9.8 (7-16) days. The number of sporocysts shed varied greatly between the opossums with maximum mean shedding occurring at 71.6 (26-112) days post-infection (DPI). Average sporocyst production was 1480 sporocysts/gram of feces (SPG). Maximum output was 37,000 SPG. Average fecal yield in captivity was 17.5g of feces/day. Opossums shed 25,900 sporocysts/day (average) and a maximum of 647,500 sporocysts/day. All opossums shed sporocysts until time of euthanasia (46-200 DPI). Histologically, numerous sporocysts were present in the lamina propria at necropsy, primarily in the proximal half of the small intestine. Sporocysts were generally in clusters within the lamina propria of the luminal two-thirds of the villi. Sporocysts were found less frequently in the epithelium. No evidence of ongoing gametogony or other development was evident.

  6. A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

    Science.gov (United States)

    Hervé, Pierre-Louis; Raliou, Mariam; Bourdieu, Christiane; Dubuquoy, Catherine; Petit-Camurdan, Agnès; Bertho, Nicolas; Eléouët, Jean-François

    2014-01-01

    In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens. PMID:24155388

  7. A novel subnucleocapsid nanoplatform for mucosal vaccination against influenza virus that targets the ectodomain of matrix protein 2.

    Science.gov (United States)

    Hervé, Pierre-Louis; Raliou, Mariam; Bourdieu, Christiane; Dubuquoy, Catherine; Petit-Camurdan, Agnès; Bertho, Nicolas; Eléouët, Jean-François; Chevalier, Christophe; Riffault, Sabine

    2014-01-01

    In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.

  8. Laminar vortex shedding behind a cooled circular cylinder

    Czech Academy of Sciences Publication Activity Database

    Trávníček, Zdeněk; Wang, A. B.; Tu, W.Y.

    2014-01-01

    Roč. 55, č. 2 (2014), s. 1-12 ISSN 0723-4864 R&D Projects: GA ČR GA14-08888S Institutional support: RVO:61388998 Keywords : vortex shedding * cooled circular cylinder * thermal effect Subject RIV: JU - Aeronautics, Aerodynamics, Aircrafts Impact factor: 1.670, year: 2014 http://link.springer.com/journal/348/55/2/page/1

  9. The economics of energy policy in China. Implications for global climate change

    International Nuclear Information System (INIS)

    Zhongxiang Zhang

    1998-01-01

    This book is the first systematic and comprehensive attempt to deal with the economic implications of carbon abatement for the Chinese economy in the light of the economics of climate change. The book provides 1) an analysis of the Chinese energy system in order to shed light on its implications for China's future CO 2 emissions; 2) a macroeconomic analysis of CO 2 emission limits for China, using a newly-developed computable general equilibrium model of the Chinese economy; and 3) a cost-effective analysis of carbon abatement options in China's electricity sector by means of a technology-oriented dynamic optimization model. (UK)

  10. Faecal shedding of canine parvovirus after modified-live vaccination in healthy adult dogs.

    Science.gov (United States)

    Freisl, M; Speck, S; Truyen, U; Reese, S; Proksch, A-L; Hartmann, K

    2017-01-01

    Since little is known about the persistence and faecal shedding of canine parvovirus (CPV) in dogs after modified-live vaccination, diagnostic tests for CPV can be difficult to interpret in the post-vaccination period. The primary aim of this study was to determine the incidence, duration and extent of CPV vaccine virus shedding in adult dogs and to investigate related factors, including the presence of protective antibodies, increase in anti-CPV antibody titres and development of any gastrointestinal side-effects. A secondary objective was to assess prevalence of CPV field virus shedding in clinically healthy dogs due to subclinical infections. One hundred adult, healthy privately owned dogs were vaccinated with a commercial CPV-2 modified-live vaccine (MLV). Faeces were tested for the presence of CPV DNA on days 0 (prior to vaccination), 3, 7, 14, 21 and 28 by quantitative real-time PCR. Pre- and post-vaccination serum titres were determined by haemagglutination inhibition on days 0, 7 and 28. Transient excretion of CPV DNA was detected in 2.0% of dogs before vaccination. About one quarter of dogs (23.0%) shed CPV DNA during the post-vaccination period, but field and vaccine virus differentiation by VP2 gene sequencing was only successful in few samples. Faecal CPV excretion occurred despite protective serum antibody titres. Post-vaccination CPV shedding was not related to adequate antibody response after vaccination or to the occurrence of gastrointestinal side-effects. Despite individual differences, CPV DNA was detectable for up to 28 days after vaccination, although the faecal CPV DNA load in these clinically healthy dogs was very low. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Scorpion sheds 'tail' to escape: consequences and implications of autotomy in scorpions (Buthidae: Ananteris.

    Directory of Open Access Journals (Sweden)

    Camilo I Mattoni

    Full Text Available Autotomy, the voluntary shedding or detachment of a body part at a determined cleavage plane, is a common anti-predation defense mechanism in several animal taxa, including arthropods. Among arachnids, autotomy has been observed in harvestmen, mites, and spiders, always involving the loss of legs. Autotomy of the opisthosoma (abdomen was recently reported in a single species of the Neotropical buthid scorpion genus Ananteris Thorell, 1891, but few details were revealed. Based on observations in the field and laboratory, examination of material in museum collections, and scanning electron microscopy, we document autotomy of the metasoma (the hind part of the opisthosoma, or 'tail' in fourteen species of Ananteris. Autotomy is more common in males than females, and has not been observed in juveniles. When the scorpion is held by the metasoma, it is voluntarily severed at the joints between metasomal segments I and II, II and III, or III and IV, allowing the scorpion to escape. After detachment, the severed metasoma moves (twitches automatically, much like the severed tail of a lizard or the severed leg of a spider, and reacts to contact, even attempting to sting. The severed surface heals rapidly, scar tissue forming in five days. The lost metasomal segments and telson cannot be regenerated. Autotomy of the metasoma and telson results in permanent loss of the posterior part of the scorpion's digestive system (the anus is situated posteriorly on metasomal segment V and the ability to inject venom by stinging. After autotomy, scorpions do not defecate and can only capture small prey items. However, males can survive and mate successfully for up to eight months in the laboratory. In spite of diminished predation ability after autotomy, survival allows males to reproduce. Autotomy in Ananteris therefore appears to be an effective, adaptive, anti-predation escape mechanism.

  12. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    International Nuclear Information System (INIS)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1–E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed

  13. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jimin, E-mail: jimin.wang@yale.edu; Li, Yue; Modis, Yorgo, E-mail: yorgo.modis@yale.edu

    2014-04-15

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1–E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.

  14. Shedding and serological patterns of dairy cows following abortions associated with Coxiella burnetii DNA detection.

    Science.gov (United States)

    Guatteo, R; Joly, A; Beaudeau, F

    2012-03-23

    To describe both shedding and serological patterns following abortions detected as being associated with Coxiella burnetii (Cb), 24 cows experiencing an abortion due to Cb were followed over a one month period. Samples taken on the day of abortion (D0) were followed 3-fold by weekly samplings from day 14 (D14) to D28 after the abortion. Milk and vaginal mucus were collected at each weekly sampling and tested using real-time PCR while blood samples were collected 2-fold on D21 and D28 and tested using ELISA. We found a very short duration of C. burnetii shedding in vaginal mucus after abortion, highlighting the need to collect samples as rapidly as possible following an abortion to avoid false negative results. In contrast with previous results, concomitancy of vaginal and mucus shedding was frequent, especially for cows shedding a high bacterial load on DO leading to the hypothesis that the clinical onset of the infection influences the modalities of Cb shedding. Lastly, serological results indicating a lack of sensitivity to detect Cb shedder cows (especially for cows for which Ct values were high) suggest that ELISA is not a useful tool to diagnose abortions at the individual level. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Zika virus reservoirs: Implications for transmission, future outbreaks, drug and vaccine development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Raj Kalkeri

    2017-10-01

    Full Text Available Zika virus (ZIKV was recently declared as a ‘Global Health Emergency’ by the World Health Organization. Various tissue reservoirs of ZIKV in infected humans and animals models have been observed, the implications of which are not known. Compared to other Flaviviruses, sexual transmission and persistence in the genitourinary tract seem to be unique to ZIKV. ZIKV persistence and shedding in bodily secretions (e.g. saliva, semen is a concern for potential disease spread and could pose challenges in diagnosis, regulatory guidelines and drug/vaccine development. Murine and non-human primate models could be useful to study the role of tissue reservoirs in the development of prophylactic or therapeutic strategies. There is a need for meta-analysis of the ZIKV infection and virus shedding data from infected patients and ZIKV animal models, and additional research is needed to fully comprehend the long term implications of tissue reservoirs on ZIKV disease pathogenesis and biology.

  16. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

    Science.gov (United States)

    Tan, Xiahui; Khalil, Najwa; Tesarik, Candice; Vanapalli, Karunasri; Yaputra, Viki; Alkhouri, Hatem; Oliver, Brian G G; Armour, Carol L; Hughes, J Margaret

    2012-04-01

    In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

  17. In Vitro Evaluation and Mechanism Analysis of the Fiber Shedding Property of Textile Pile Debridement Materials

    Directory of Open Access Journals (Sweden)

    Yijun Fu

    2016-04-01

    Full Text Available Fiber shedding is a critical problem in biomedical textile debridement materials, which leads to infection and impairs wound healing. In this work, single fiber pull-out test was proposed as an in vitro evaluation for the fiber shedding property of a textile pile debridement material. Samples with different structural design (pile densities, numbers of ground yarns and coating times were prepared and estimated under this testing method. Results show that single fiber pull-out test offers an appropriate in vitro evaluation for the fiber shedding property of textile pile debridement materials. Pull-out force for samples without back-coating exhibited a slight escalating trend with the supplement in pile density and number of ground yarn plies, while back-coating process significantly raised the single fiber pull-out force. For fiber shedding mechanism analysis, typical pull-out behavior and failure modes of the single fiber pull-out test were analyzed in detail. Three failure modes were found in this study, i.e., fiber slippage, coating point rupture and fiber breakage. In summary, to obtain samples with desirable fiber shedding property, fabric structural design, preparation process and raw materials selection should be taken into full consideration.

  18. Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition.

    Science.gov (United States)

    Ramchandani, Meena; Selke, Stacy; Magaret, Amalia; Barnum, Gail; Huang, Meei-Li Wu; Corey, Lawrence; Wald, Anna

    2017-11-25

    Herpes simplex virus type 2 (HSV-2) is a prevalent infection with great variability in clinical and virological manifestations among individuals. This prospective cohort study aims to evaluate the natural history of HSV-2 reactivation in the genital area in the same group of women over time. Eighteen immunocompetent HSV-2 seropositive women were evaluated for viral shedding for 70 consecutive days within a median of 8 months (range 1-24 months) of HSV-2 acquisition and again approximately 2.5 years later from the original study. Participants obtained daily swabs of genital secretions for HSV PCR and recorded genital symptoms. The viral shedding rate was 29% during the initial study and 19% in the follow-up study (32% reduction, P=0.019). Subclinical shedding rate also decreased from 24% to 13% (37% reduction, P=0.032), as did the rate of days with genital lesions from 22% to 15% (33% reduction, P=0.24). The mean copy number during viral shedding remained unchanged over time at 4.8 log 10 c/mL (SD=2.0 and 1.6 during each study, respectively, P=0.33). Women with high viral shedding rates in the past were likely to continue to have high shedding rates (r=0.63, P=0.005). Despite some reduction, high viral shedding rates persist in women with genital HSV-2 greater than 2 years after acquisition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Avian bornavirus in free-ranging waterfowl: prevalence of antibodies and cloacal shedding of viral RNA.

    Science.gov (United States)

    Delnatte, Pauline; Nagy, Éva; Ojkic, Davor; Leishman, David; Crawshaw, Graham; Elias, Kyle; Smith, Dale A

    2014-07-01

    We surveyed free-ranging Canada Geese (Branta canadensis), Trumpeter Swans (Cygnus buccinator), Mute Swans (Cygnus olor), and Mallards (Anas platyrhynchos) to estimate the prevalence of antibodies to avian bornavirus (ABV) and of cloacal shedding of ABV RNA in southern Ontario, Canada. Blood samples and cloacal swabs were collected from 206 free-ranging Canada Geese, 135 Trumpeter Swans, 75 Mute Swans, and 208 Mallards at 10 main capture sites between October 2010 and May 2012. Sera were assessed for antibodies against ABV by enzyme-linked immunosorbent assay and swabs were evaluated for ABV RNA using real-time reverse-transcription PCR. Serum antibodies were detected in birds from all four species and at each sampling site. Thirteen percent of the geese caught on the Toronto Zoo site shed ABV RNA in feces compared with 0% in geese sampled at three other locations. The proportions of shedders among Mute Swans, Trumpeter Swans, and Mallards were 9%, 0%, and 0%, respectively. Birds that were shedding viral RNA were more likely to have antibodies against ABV and to have higher antibody levels than those that were not, although many birds with antibodies were not shedding. We confirmed that exposure to, or infection with, ABV is widespread in asymptomatic free-ranging waterfowl in Canada; however, the correlation between cloacal shedding, presence of antibodies, and presence of disease is not fully understood.

  20. Effect of perforation on flow past a conic cylinder at Re = 100: vortex-shedding pattern and force history

    Science.gov (United States)

    Lin, L. M.; Zhong, X. F.; Wu, Y. X.

    2017-09-01

    The flow past a circular-section cylinder with a conic shroud perforated with four holes at the peak was simulated numerically at Re=100 , considering two factors, viz. the angle of attack and the diameter of the holes. The effects of the perforated conic shroud on the vortex shedding pattern in the near wake was mainly investigated, as well as the time history of the drag and lift forces. In the investigated parameter space, three flow regimes were generally identified, corresponding to weak, moderate, and strong disturbance effects. In regime I, the wake can mainly be described by alternately shedding Kármán or Kármán-like vortices. In regime II, the spanwise vortices are obviously disturbed along the span due to the appearance of additional vorticity components and their interactions with the spanwise vortices, but still shed in synchronization along the spanwise direction. In regime III, the typical Kármán vortices partially or totally disappear, and some new vortex shedding patterns appear, such as Ω -type, obliquely shedding, and crossed spanwise vortices with opposite sign. Corresponding to these complex vortex shedding patterns in the near wake, the fluid forces no longer oscillate regularly at a single vortex shedding frequency, but rather with a lower modulation frequency and multiple amplitudes. An overview of these flow regimes is presented.

  1. Fly proof net shed for livestock: A novel concept of physical barrier for integrated management of Culicoides spp. (Diptera: Ceratopogonidae

    Directory of Open Access Journals (Sweden)

    B. W. Narladkar

    2014-11-01

    Full Text Available Aim: An age old and time tested technique of mosquito net requiring no energy, used by humans since prehistoric period was the inspiration behind this novel technique of fly proof net shed for livestock. With the aim to develop similar type of net shed for animals, which will protect them at night from biting of range of insects from Culicoides midges to mosquitoes, research was undertaken. Materials and Methods: Net shed with pitch roof (gable type was erected for use of livestock. The open inlet area was covered with 40 mesh size wire net. The roof at attic level was fitted with hurricane type of ventilator. Shed was used for animals at night hours only. vane anemometer was used for estimation of temperature and wind related parameters. Thermal humidity index (THI and air changes were calculated as per the standard formulas. Based on these parameters suitability of shed was judged. Results: It was observed that, due to netting of the shed population of Culicoides and other flies and incidences of their bites at night hours were considerably lowered. As a result, animals were found comfortable, and their body movements undertaken for wiping off these flies were significantly reduced from 196.50 to 22.16. All it accrued to increased milk yield to the tune of 18.97% in the net shed buffaloes as against control shed. Studies on suitability and comfort to animals were tested by estimating THI and air changes per hour in the net shed, which also revealed the estimates in comfortable regimen and ventilation, remained not much affected despite of netting. Other parameters studied for testing its more accuracy by taking other species of animals as kids, for them also, shed was found suitable through estimation of various physiological and behavioral parameters. Finally, the efficacy of shed was judged on the basis of cost effectiveness. Highly encouraging results on the above said parameters endorsed the effectiveness of the technique. Conclusion: A

  2. Studies on Nanoparticle Based Avian Influenza Vaccines to Present Immunogenic Epitopes of the Virus with Concentration on Ectodomain of Matrix 2 (M2e) Protein

    Science.gov (United States)

    Babapoor Dighaleh, Sankhiros

    2011-12-01

    Avian influenza is an infectious disease of avian species caused by type A influenza viruses with a significant economic impact on the poultry industry. Vaccination is the main prevention strategy in many countries worldwide. However, available vaccines elicit antibodies against two major surface protein of the virus hemagglutinin (HA) and neuraminidase (NA), where they constantly change by point mutations. Influenza viruses can also easily undergo gene reassortment. Therefore, to protect chickens against new strain of avian influenza virus, as well as control and prevent virus spread among farms, new vaccines needed to be designed which is a tedious, time consuming and expensive. Recently, conserved regions of the influenza genome have been evaluated as possible universal vaccines to eliminate constant vaccine updates based on circulating virus. In this study, peptide nanotechnology was used to generate vaccine nanoparticles that carry the highly conserved external domain of matrix 2 protein (M2e). These nanoparticles presented M2e in monomeric or tetrameric forms, designated as PSC-M2e-CH and BNSC-M2eN-CH. respectively. First, to demonstrate immunogenicity of these nanoparticles, we measured anti-M2e antibody in chickens, particularly when a high dose was applied. Prior to vaccination-challenge study, the challenge dose were determined by oculonasal inoculation of 10 6 EID50 or 107.7 EID50 of low pathogenicity AI virus HSN2 followed by measuring cloacal and tracheal virus shedding. A biphasic virus shedding pattern was observed with two peaks of virus shedding at days 4 and 8 for both tracheal and cloacal swabs. The chickens infected with 107.7 EID50 had significant virus shedding as compared with 106 EID50. Based on results of mentioned studies, a vaccination-challenge study was conducted by using 75mug of each vaccine construct per inoculation (with and without adjuvant) and higher dose of virus for challenge. BN5C-M2e-CH with adjuvant significantly reduced the

  3. Dynamics of Salmonella Shedding and Welfare of Hens in Free-Range Egg Production Systems

    Science.gov (United States)

    Gole, Vaibhav C.; Woodhouse, Rebecca; Caraguel, Charles; Moyle, Talia; Rault, Jean-Loup; Sexton, Margaret

    2016-01-01

    ABSTRACT The current study investigated the effect of environmental stressors (i.e., weather changes) on Salmonella shedding in free-range production systems and the correlations with behavioral and physiological measures (i.e., fecal glucocorticoid metabolites). This involved longitudinal and point-in-time surveys of Salmonella shedding and environmental contamination on four commercial free-range layer farms. The shedding of Salmonella was variable across free-range farms and in different seasons. There was no significant effect of season on the Salmonella prevalence during this investigation. In this study, the combined Salmonella most probable number (MPN) counts in environmental (including feces, egg belt, dust, nest box, and ramp) samples were highest in samples collected during the summer season (4th sampling, performed in February). The predominant serovars isolated during this study were Salmonella enterica serovar Mbandaka and Salmonella enterica serovar Typhimurium phage types 135 and 135a. These two phage types were involved in several egg product-related Salmonella outbreaks in humans. Multilocus variable-number tandem-repeat analysis (MLVA) results indicated that MLVA types detected from human food poisoning cases exhibited MLVA patterns similar to the strains isolated during this study. All Salmonella isolates (n = 209) were tested for 15 different genes involved in adhesion, invasion, and survival of Salmonella spp. We also observed variations for sopA, ironA, and misL. There were no positive correlations between fecal corticosterone metabolite (FCM) and Salmonella prevalence and/or shedding in feces. Also, there were no positive correlations between Salmonella prevalence and Salmonella count (log MPN) and any of the other welfare parameters. IMPORTANCE In this study, the welfare of laying hens and Salmonella shedding were compared over a prolonged period of time in field conditions. This study investigated the long-term shedding of Salmonella

  4. Dynamics of Salmonella Shedding and Welfare of Hens in Free-Range Egg Production Systems.

    Science.gov (United States)

    Gole, Vaibhav C; Woodhouse, Rebecca; Caraguel, Charles; Moyle, Talia; Rault, Jean-Loup; Sexton, Margaret; Chousalkar, Kapil

    2017-03-01

    The current study investigated the effect of environmental stressors (i.e., weather changes) on Salmonella shedding in free-range production systems and the correlations with behavioral and physiological measures (i.e., fecal glucocorticoid metabolites). This involved longitudinal and point-in-time surveys of Salmonella shedding and environmental contamination on four commercial free-range layer farms. The shedding of Salmonella was variable across free-range farms and in different seasons. There was no significant effect of season on the Salmonella prevalence during this investigation. In this study, the combined Salmonella most probable number (MPN) counts in environmental (including feces, egg belt, dust, nest box, and ramp) samples were highest in samples collected during the summer season (4th sampling, performed in February). The predominant serovars isolated during this study were Salmonella enterica serovar Mbandaka and Salmonella enterica serovar Typhimurium phage types 135 and 135a. These two phage types were involved in several egg product-related Salmonella outbreaks in humans. Multilocus variable-number tandem-repeat analysis (MLVA) results indicated that MLVA types detected from human food poisoning cases exhibited MLVA patterns similar to the strains isolated during this study. All Salmonella isolates ( n = 209) were tested for 15 different genes involved in adhesion, invasion, and survival of Salmonella spp. We also observed variations for sopA , ironA , and misL There were no positive correlations between fecal corticosterone metabolite (FCM) and Salmonella prevalence and/or shedding in feces. Also, there were no positive correlations between Salmonella prevalence and Salmonella count (log MPN) and any of the other welfare parameters. IMPORTANCE In this study, the welfare of laying hens and Salmonella shedding were compared over a prolonged period of time in field conditions. This study investigated the long-term shedding of Salmonella serovars in

  5. Vortex shedding induced by a solitary wave propagating over a submerged vertical plate

    International Nuclear Information System (INIS)

    Lin Chang; Ho, T.-C.; Chang, S.-C.; Hsieh, S.-C.; Chang, K.-A.

    2005-01-01

    Experimental study was conducted on the vortex shedding process induced by the interaction between a solitary wave and a submerged vertical plate. Particle image velocimetry (PIV) was used for quantitative velocity measurement while a particle tracing technique was used for qualitative flow visualization. Vortices are generated at the tip of each side of the plate. The largest vortices at each side of the plate eventually grow to the size of the water depth. Although the fluid motion under the solitary wave is only translatory, vortices are shed in both the upstream and downstream directions due to the interaction of the generated vortices as well as the vortices with the plate and the bottom. The process can be divided into four phases: the formation of a separated shear layer, the generation and shedding of vortices, the formation of a vertical jet, and the impingement of the jet onto the free surface. Similarity velocity profiles were found both in the separated shear layer and in the vertical jet

  6. A garment for use in the operating theatre: the effect upon bacterial shedding.

    Science.gov (United States)

    Dankert, J; Zijlstra, J B; Lubberding, H

    1979-02-01

    In operating theatres the air is mainly contaminated with bacteria shed from the human skin. The emission of bacteria can be prevented by wearing clothing of impervious material, while normal cotton clothing does not decrease the shedding of bacteria. In this study shedding of viable bacteria from 20 test-persons wearing an operating theatre suit, composed of 65% polyester and 35% cotton (Diolen), was investigated in a test-chamber and compared with that when normal clothing was worn. The use of this operating-theatre suit resulted in a significant reduction (50--75%) in the number of bacteria-carrying particles in the air of the test-chamber and in an operating room when everyone present wore this suit. A combination of the suit with knee-high boots showed a further reduction in the dispersal of colony forming units. The dispersion from female subjects wearing an operating-theatre frock was significantly higher than when wearing an operating-theatre suit.

  7. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding

    Science.gov (United States)

    Corey, Lawrence

    2015-01-01

    SUMMARY Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward. PMID:26561565

  8. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding.

    Science.gov (United States)

    Johnston, Christine; Corey, Lawrence

    2016-01-01

    Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. The economics of energy policy in China. Implications for global climate change

    Energy Technology Data Exchange (ETDEWEB)

    Zhongxiang Zhang [Groningen Univ., Dept. of Economics and Public Finance, Groningen (Netherlands)]|[Chinese Academy of Social Sciences, Centre for Environment and Development, Beijing (China)

    1998-08-01

    This book is the first systematic and comprehensive attempt to deal with the economic implications of carbon abatement for the Chinese economy in the light of the economics of climate change. The book provides 1) an analysis of the Chinese energy system in order to shed light on its implications for China`s future CO{sub 2} emissions; 2) a macroeconomic analysis of CO{sub 2} emission limits for China, using a newly-developed computable general equilibrium model of the Chinese economy; and 3) a cost-effective analysis of carbon abatement options in China`s electricity sector by means of a technology-oriented dynamic optimization model. (UK)

  10. Genital Herpes Simplex Virus Type 2 Shedding Among Adults With and Without HIV Infection in Uganda.

    Science.gov (United States)

    Phipps, Warren; Nakku-Joloba, Edith; Krantz, Elizabeth M; Selke, Stacy; Huang, Meei-Li; Kambugu, Fred; Orem, Jackson; Casper, Corey; Corey, Lawrence; Wald, Anna

    2016-02-01

    Despite the high prevalence of herpes simplex virus type 2 (HSV-2) in sub-Saharan Africa, the natural history of infection among Africans is not well characterized. We evaluated the frequency of genital HSV shedding in HIV-seropositive and HIV-seronegative men and women in Uganda. Ninety-three HSV-2-seropositive Ugandan adults collected anogenital swab specimens for HSV DNA quantification by polymerase chain reaction 3 times daily for 6 weeks. HSV-2 was detected from 2484 of 11 283 swab specimens collected (22%), with a median quantity of 4.3 log10 HSV copies/mL (range, 2.2-8.9 log10 HSV copies/mL). Genital lesions were reported on 749 of 3875 days (19%), and subclinical HSV shedding was detected from 1480 of 9113 swab specimens (16%) collected on days without lesions. Men had higher rates of total HSV shedding (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.3-2.9]; P genital lesions (RR, 2.1 [95% CI, 1.2-3.4]; P = .005), compared with women. No differences in shedding rates or lesion frequency were observed based on HIV serostatus. HSV-2 shedding frequency and quantity are high among HSV-2-seropositive adults in sub-Saharan Africa, including persons with and those without HIV infection. Shedding rates were particularly high among men, which may contribute to the high prevalence of HSV-2 and early acquisition among African women. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. A dynamical systems analysis of the kinematics of time-periodic vortex shedding past a circular cylinder

    Science.gov (United States)

    Ottino, Julio M.

    1991-01-01

    Computer flow simulation aided by dynamical systems analysis is used to investigate the kinematics of time-periodic vortex shedding past a two-dimensional circular cylinder in the context of the following general questions: (1) Is a dynamical systems viewpoint useful in the understanding of this and similar problems involving time-periodic shedding behind bluff bodies; and (2) Is it indeed possible, by adopting such a point of view, to complement previous analyses or to understand kinematical aspects of the vortex shedding process that somehow remained hidden in previous approaches. We argue that the answers to these questions are positive. Results are described.

  12. Molecular epidemiology of Avian Rotaviruses Group A and D shed by different bird species in Nigeria.

    Science.gov (United States)

    Pauly, Maude; Oni, Oluwole O; Sausy, Aurélie; Owoade, Ademola A; Adeyefa, Christopher A O; Muller, Claude P; Hübschen, Judith M; Snoeck, Chantal J

    2017-06-12

    Avian rotaviruses (RVs) cause gastrointestinal diseases of birds worldwide. However, prevalence, diversity, epidemiology and phylogeny of RVs remain largely under-investigated in Africa. Fecal samples from 349 birds (158 symptomatic, 107 asymptomatic and 84 birds without recorded health status) were screened by reverse transcription PCR to detect RV groups A and D (RVA and RVD). Partial gene sequences of VP4, VP6, VP7 and NSP4 for RVA, and of VP6 and VP7 for RVD were obtained and analyzed to infer phylogenetic relationship. Fisher's exact test and logistic regression were applied to identify factors potentially influencing virus shedding in chickens. A high prevalence of RVA (36.1%; 126/349) and RVD (31.8%; 111/349) shedding was revealed in birds. In chickens, RV shedding was age-dependent and highest RVD shedding rates were found in commercial farms. No negative health effect could be shown, and RVA and RVD shedding was significantly more likely in asymptomatic chickens: RVA/RVD were detected in 51.9/48.1% of the asymptomatic chickens, compared to 18.9/29.7% of the symptomatic chickens (p epidemiology, diversity and classification of avian RVA and RVD in Nigeria. We show that cross-species transmission of host permissive RV strains occurs when different bird species are mixed.

  13. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  14. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

  15. Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.

    Science.gov (United States)

    Hughes, K R; Harnisch, L C; Alcon-Giner, C; Mitra, S; Wright, C J; Ketskemety, J; van Sinderen, D; Watson, A J M; Hall, L J

    2017-01-01

    Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. © 2017 The Authors.

  16. Voltage Stability Control of Electrical Network Using Intelligent Load Shedding Strategy Based on Fuzzy Logic

    Directory of Open Access Journals (Sweden)

    Houda Jouini

    2010-01-01

    Full Text Available As a perspective to ensure the power system stability and to avoid the vulnerability leading to the blackouts, several preventive and curative means are adopted. In order to avoid the voltage collapse, load shedding schemes represent a suitable action to maintain the power system service quality and to control its vulnerability. In this paper, we try to propose an intelligent load shedding strategy as a new approach based on fuzzy controllers. This strategy was founded on the calculation of generated power sensitivity degree related to those injected at different network buses. During the fault phase, fuzzy controller algorithms generate monitor vectors ensuring a precalculated load shedding ratio in the purpose to reestablish the power balance and conduct the network to a new steady state.

  17. An implementation of particle swarm optimization to evaluate optimal under-voltage load shedding in competitive electricity markets

    Science.gov (United States)

    Hosseini-Bioki, M. M.; Rashidinejad, M.; Abdollahi, A.

    2013-11-01

    Load shedding is a crucial issue in power systems especially under restructured electricity environment. Market-driven load shedding in reregulated power systems associated with security as well as reliability is investigated in this paper. A technoeconomic multi-objective function is introduced to reveal an optimal load shedding scheme considering maximum social welfare. The proposed optimization problem includes maximum GENCOs and loads' profits as well as maximum loadability limit under normal and contingency conditions. Particle swarm optimization (PSO) as a heuristic optimization technique, is utilized to find an optimal load shedding scheme. In a market-driven structure, generators offer their bidding blocks while the dispatchable loads will bid their price-responsive demands. An independent system operator (ISO) derives a market clearing price (MCP) while rescheduling the amount of generating power in both pre-contingency and post-contingency conditions. The proposed methodology is developed on a 3-bus system and then is applied to a modified IEEE 30-bus test system. The obtained results show the effectiveness of the proposed methodology in implementing the optimal load shedding satisfying social welfare by maintaining voltage stability margin (VSM) through technoeconomic analyses.

  18. Cervical Shedding of HIV-1 RNA Among Women With Low Levels of Viremia While Receiving Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Neely, Michael N.; Benning, Lorie; Xu, Jiaao; Strickler, Howard D.; Greenblatt, Ruth M.; Minkoff, Howard; Young, Mary; Bremer, James; Levine, Alexandra M.; Kovacs, Andrea

    2011-01-01

    Background Among women with low o r undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. Methods We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women’s Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. Results Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). Conclusions This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners. PMID:17106279

  19. Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy.

    Science.gov (United States)

    Kwok, Hang Fai; Botkjaer, Kenneth A; Tape, Christopher J; Huang, Yanchao; McCafferty, John; Murphy, Gillian

    2014-06-01

    We previously showed that a human anti-TACE antibody, D1(A12), is a potent inhibitor of TNF-α converting enzyme (TACE) ectodomain proteolysis and has pharmacokinetic properties suitable for studies of the inhibition of TACE-dependent growth factor shedding in relation to possible therapeutic applications. However, the lack of murine TACE immunoreactivity limits pre-clinical in vivo studies to human xenograft models which are poor analogies to in situ pathology and are not considered clinically predictive. Here, to overcome these limitations, we set out to develop a 'mouse and human cross-reactive' specific anti-TACE antibody. We first re-investigated the originally selected anti-TACE ectodomain phage-display clones, and isolated a lead 'mouse-human cross-reactive' anti-TACE scFv, clone A9. We reformatted scFv-A9 into an IgG2 framework for comprehensive biochemical and cellular characterization and further demonstrated that A9 is an exosite TACE inhibitor. However, surface plasmon resonance analysis and quenched-fluorescent (QF) peptide assay indicated that IgG reformatting of A9 caused low binding affinity and an 80-fold reduction in TACE ectodomain inhibition, severely limiting its efficacy. To address this, we constructed second generation phage-display randomization libraries focused on the complementarity-determining region 3, and carried out affinity selections shuffling between human and mouse TACE ectodomain as antigen in addition to an off-rate selection to increase the chance of affinity improvement. The bespoke 'three-step' selections enabled a 100-fold affinity enhancement of A9 IgG, and also improved its IC50 in a QF peptide assay to 0.2 nM. In human and mouse cancer cell assays, matured A9 IgG showed significant cell-surface TACE inhibition as a monotherapy or combination therapy with chemotherapeutic agent. Collectively, these data suggest that we successfully developed an exosite inhibitor of TACE with sub-nanomolar affinity, which possesses both

  20. Effect of a probiotic on prevention of diarrhea and Clostridium difficile and Clostridium perfringens shedding in foals

    DEFF Research Database (Denmark)

    Schoster, Angelika; Staempfli, H R; Abrahams, M

    2015-01-01

    of incidence and duration of diarrhea and fecal shedding of Clostridium perfringens and Clostridium difficile between treatment and age groups. RESULTS: The overall incidence of diarrhea was 41 of 72 (59%) and did not differ (P = 0.37) between treatment groups. Foals treated with probiotics were more likely...... of C. perfringens shedding was 55% with no difference between treatment groups (P = 0.23). The prevalence of C. difficile shedding was 11%. CONCLUSION AND CLINICAL IMPORTANCE: There was no benefit of administering a 3-week course of probiotics, but potential adverse effects were noted. Whether...

  1. Factors associated with Salmonella shedding among equine colic patients at a veterinary teaching hospital.

    Science.gov (United States)

    Kim, L M; Morley, P S; Traub-Dargatz, J L; Salman, M D; Gentry-Weeks, C

    2001-03-01

    To evaluate factors potentially associated with fecal Salmonella shedding among equine patients hospitalized for colic at a veterinary teaching hospital and to determine the effects of probiotic treatment on fecal Salmonella shedding and clinical signs. Longitudinal study and controlled trial. 246 equine colic patients. History and medical information were obtained from patient records. Fecal and environmental samples were submitted for aerobic bacterial culture for Salmonella enterica. Fifty-one patients were treated with a commercially available probiotic; 46 were treated with a placebo. Logistic regression was used to evaluate data. Salmonella organisms were detected in feces from 23 (9%) patients at least once during hospitalization. Patients were more likely to shed Salmonella organisms if diarrhea was evident equine patients hospitalized at a veterinary teaching hospital because of colic and that pathogen monitoring in patients and the hospital environment and use of barrier nursing precautions for equine colic patients are beneficial.

  2. Extended viral shedding of a low pathogenic avian influenza virus by striped skunks (Mephitis mephitis.

    Directory of Open Access Journals (Sweden)

    J Jeffrey Root

    Full Text Available BACKGROUND: Striped skunks (Mephitis mephitis are susceptible to infection with some influenza A viruses. However, the viral shedding capability of this peri-domestic mammal and its potential role in influenza A virus ecology are largely undetermined. METHODOLOGY/PRINCIPAL FINDINGS: Striped skunks were experimentally infected with a low pathogenic (LP H4N6 avian influenza virus (AIV and monitored for 20 days post infection (DPI. All of the skunks exposed to H4N6 AIV shed large quantities of viral RNA, as detected by real-time RT-PCR and confirmed for live virus with virus isolation, from nasal washes and oral swabs (maximum ≤ 10(6.02 PCR EID50 equivalent/mL and ≤ 10(5.19 PCR EID50 equivalent/mL, respectively. Some evidence of potential fecal shedding was also noted. Following necropsy on 20 DPI, viral RNA was detected in the nasal turbinates of one individual. All treatment animals yielded evidence of a serological response by 20 DPI. CONCLUSIONS/SIGNIFICANCE: These results indicate that striped skunks have the potential to shed large quantities of viral RNA through the oral and nasal routes following exposure to a LP AIV. Considering the peri-domestic nature of these animals, along with the duration of shedding observed in this species, their presence on poultry and waterfowl operations could influence influenza A virus epidemiology. For example, this species could introduce a virus to a naive poultry flock or act as a trafficking mechanism of AIV to and from an infected poultry flock to naive flocks or wild bird populations.

  3. Genital Shedding of Herpes Simplex Virus Among Symptomatic and Asymptomatic Persons with HSV-2 Infection

    Science.gov (United States)

    Tronstein, Elizabeth; Johnston, Christine; Huang, Meei-Li; Selke, Stacy; Magaret, Amalia; Warren, Terri; Corey, Lawrence; Wald, Anna

    2011-01-01

    Context Since HSV-2 antibody tests have become commercially available, an increasing number of persons learn that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain. Objective To evaluate the virologic and clinical course of HSV genital shedding among participants with symptomatic and asymptomatic HSV-2 infection. Design, Setting and Participants Cohort of 498 immunocompetent HSV-2 seropositive persons enrolled in prospective studies of genital HSV shedding at the University of Washington Virology Research Clinic, Seattle, Washington, and Westover Heights Clinic in Portland, Oregon, between 1992 and 2008. Each participant obtained daily self-collected swabs of genital secretions for ≥ 30 days. Main Outcome Measurement The rate of viral shedding measured by quantitative real-time fluorescence polymerase chain reaction (PCR) for HSV DNA from genital swabs. Results HSV was detected on 4,753 of 23,683 days (20.1%; 95% CI, 18.3 to 22.0) in persons with symptomatic genital HSV-2 infection compared with 519 of 5,070 days (10.2%; 95% CI, 7.7 to 13.6) in persons with asymptomatic infection, pgenital viral shedding among persons with symptomatic genital HSV-2 infection compared with 85 of 519 days (16.4%; 95% CI, 11.2 to 23.9) among persons with asymptomatic infection, pgenital tract less frequently than persons with symptomatic infection, but much of the difference is attributable to less frequent genital lesions, as lesions are accompanied by frequent viral shedding. PMID:21486977

  4. A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition.

    Science.gov (United States)

    Liu, Jin; Xu, Congfeng; Hsu, Li-Chung; Luo, Yunping; Xiang, Rong; Chuang, Tsung-Hsien

    2010-02-01

    Toll-like receptors play important roles in regulating immunity against microbial infections. Toll-like receptor 8 (TLR8) belongs to a subfamily comprising TLR7, TLR8 and TLR9. Human TLR8 mediates anti-viral immunity by recognizing ssRNA viruses, and triggers potent anti-viral and antitumor immune responses upon ligation by synthetic small molecular weight ligands. Interestingly, distinct from human TLR8, mouse TLR8 was not responsive to ligand stimulation in the absence of polyT-oligodeoxynucleotides (polyT-ODN). The molecular basis for this distinct ligand recognition is still unclear. In the present study, we compared the activation of TLR8 from different species including mouse, rat, human, bovine, porcine, horse, sheep, and cat by ligand ligations. Only the TLR8s from the rodent species (i.e., mouse and rat TLR8s) failed to respond to ligand stimulation in the absence of polyT-ODN. Multiple sequence alignment analysis suggested that these two rodent TLR8s lack a five-amino-acid motif that is conserved in the non-rodent species with varied sequence. This small motif is located in an undefined region of the hTLR8 ectodomain, immediately following LRR-14. Deletion mutation analysis suggested that this motif is essential for the species-specific ligand recognition of hTLR8, whereas it is not required for self-dimerization and intracellular localization of this receptor. (c) 2009 Elsevier Ltd. All rights reserved.

  5. Acoustically levitated dancing drops: Self-excited oscillation to chaotic shedding

    Science.gov (United States)

    Lin, Po-Cheng; I, Lin

    2016-02-01

    We experimentally demonstrate self-excited oscillation and shedding of millimeter-sized water drops, acoustically levitated in a single-node standing waves cavity, by decreasing the steady acoustic wave intensity below a threshold. The perturbation of the acoustic field by drop motion is a possible source for providing an effective negative damping for sustaining the growing amplitude of the self-excited motion. Its further interplay with surface tension, drop inertia, gravity and acoustic intensities, select various self-excited modes for different size of drops and acoustic intensity. The large drop exhibits quasiperiodic motion from a vertical mode and a zonal mode with growing coupling, as oscillation amplitudes grow, until falling on the floor. For small drops, chaotic oscillations constituted by several broadened sectorial modes and corresponding zonal modes are self-excited. The growing oscillation amplitude leads to droplet shedding from the edges of highly stretched lobes, where surface tension no longer holds the rapid expanding flow.

  6. A pressure-gradient mechanism for vortex shedding in constricted channels

    Science.gov (United States)

    Boghosian, M. E.; Cassel, K. W.

    2013-01-01

    Numerical simulations of the unsteady, two-dimensional, incompressible Navier–Stokes equations are performed for a Newtonian fluid in a channel having a symmetric constriction modeled by a two-parameter Gaussian distribution on both channel walls. The Reynolds number based on inlet half-channel height and mean inlet velocity ranges from 1 to 3000. Constriction ratios based on the half-channel height of 0.25, 0.5, and 0.75 are considered. The results show that both the Reynolds number and constriction geometry have a significant effect on the behavior of the post-constriction flow field. The Navier–Stokes solutions are observed to experience a number of bifurcations: steady attached flow, steady separated flow (symmetric and asymmetric), and unsteady vortex shedding downstream of the constriction depending on the Reynolds number and constriction ratio. A sequence of events is described showing how a sustained spatially growing flow instability, reminiscent of a convective instability, leads to the vortex shedding phenomenon via a proposed streamwise pressure-gradient mechanism. PMID:24399860

  7. Emergency Load Shedding Strategy Based on Sensitivity Analysis of Relay Operation Margin against Cascading Events

    DEFF Research Database (Denmark)

    Liu, Zhou; Chen, Zhe; Sun, Haishun Sun

    2012-01-01

    the runtime emergent states of related system component. Based on sensitivity analysis between the relay operation margin and power system state variables, an optimal load shedding strategy is applied to adjust the emergent states timely before the unwanted relay operation. Load dynamics is also taken...... into account to compensate load shedding amount calculation. And the multi-agent technology is applied for the whole strategy implementation. A test system is built in real time digital simulator (RTDS) and has demonstrated the effectiveness of the proposed strategy.......In order to prevent long term voltage instability and induced cascading events, a load shedding strategy based on the sensitivity of relay operation margin to load powers is discussed and proposed in this paper. The operation margin of critical impedance backup relay is defined to identify...

  8. Coxiella burnetii Shedding Routes and Antibody Response after Outbreaks of Q Fever-Induced Abortion in Dairy Goat Herds▿

    OpenAIRE

    Rousset, Elodie; Berri, Mustapha; Durand, Benoit; Dufour, Philippe; Prigent, Myriam; Delcroix, Thibault; Touratier, Anne; Rodolakis, Annie

    2008-01-01

    Q fever is a zoonosis caused by Coxiella burnetii, a bacterium largely carried by ruminants and shed into milk, vaginal mucus, and feces. The main potential hazard to humans and animals is due to shedding of bacteria that can then persist in the environment and be aerosolized. The purpose of this study was to evaluate shedding after an outbreak of Q fever abortion in goat herds and to assess the relationship with the occurrence of abortions and antibody responses. Aborting and nonaborting goa...

  9. The Influence of Load Shedding on the Productivity of Hotel Staff in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    Henriëtte STEENKAMP

    2016-07-01

    Full Text Available In South Africa, ESCOM is the country’s main electricity supplier. Since 2008, Eskom has implemented load shedding on an ongoing basis as a result of insufficient electricity supply to meet the demands of all its customers. Owing to the fact that many organisations across South Africa are depended on electricity in order to function, previous research studies show that the wide-spread impact of load shedding has had an adverse on the sustainability of many of these organisations. Among these organisations are those based in the hospitality industry – imperative in relation to the stimulation of the national economy; directly related to tourism. Albeit the aforementioned, the sustainability of organisations in the hospitality industry is also heavily dependent on the productivity of their employees. For this research study the influence of load shedding on the productivity of the staff in the hospitality industry was investigated within one particular hotel (Hotel X based in Cape Town. Empirical research was deployed, making use of a mixed methods approach to obtain both quantitative data and qualitative data from respondents. Stemming from the findings it was found that load shedding did have an adverse influence on the productivity of staff in Hotel X, despite the fact that affordable measures were put in place to mitigate the disruptions caused by load shedding. Moreover, the latter dispensation was found to have an inadvertently adverse influence on the overall sustainability of Hotel X on the long run.

  10. A Lagrangian analysis of a two-dimensional airfoil with vortex shedding

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Doug; Cardwell, Blake; Mohseni, Kamran [Department of Aerospace Engineering Sciences, University of Colorado, Boulder, CO 80309-0429 (United States)], E-mail: Mohseni@colorado.edu

    2008-08-29

    Using invariant material manifolds and flow topology, the flow behavior and structure of flow around a two-dimensional Eppler 387 airfoil is examined with an emphasis on vortex shedding and the time-dependent reattachment profile. The examination focuses on low Reynolds number (Re = 60 000) flow at several angles of attack. Using specialized software, we identify invariant manifolds in the flow and use these structures to illuminate the process of vortex formation and the periodic behavior of the reattachment profile. Our analysis concludes with a topological view of the flow, including fixed points and a discussion of phase plots and the frequency spectrum of several key points in the flow. The behavior of invariant manifolds directly relates to the flow topology and illuminates some aspects seen in phase space during vortex shedding. Furthermore, it highlights the reattachment behavior in ways not seen before.

  11. A Lagrangian analysis of a two-dimensional airfoil with vortex shedding

    International Nuclear Information System (INIS)

    Lipinski, Doug; Cardwell, Blake; Mohseni, Kamran

    2008-01-01

    Using invariant material manifolds and flow topology, the flow behavior and structure of flow around a two-dimensional Eppler 387 airfoil is examined with an emphasis on vortex shedding and the time-dependent reattachment profile. The examination focuses on low Reynolds number (Re = 60 000) flow at several angles of attack. Using specialized software, we identify invariant manifolds in the flow and use these structures to illuminate the process of vortex formation and the periodic behavior of the reattachment profile. Our analysis concludes with a topological view of the flow, including fixed points and a discussion of phase plots and the frequency spectrum of several key points in the flow. The behavior of invariant manifolds directly relates to the flow topology and illuminates some aspects seen in phase space during vortex shedding. Furthermore, it highlights the reattachment behavior in ways not seen before

  12. Shedding of Ebola Virus Surface Glycoprotein Is a Mechanism of Self-regulation of Cellular Cytotoxicity and Has a Direct Effect on Virus Infectivity.

    Science.gov (United States)

    Dolnik, Olga; Volchkova, Valentina A; Escudero-Perez, Beatriz; Lawrence, Philip; Klenk, Hans-Dieter; Volchkov, Viktor E

    2015-10-01

    The surface glycoprotein (GP) is responsible for Ebola virus (EBOV) attachment and membrane fusion during virus entry. Surface expression of highly glycosylated GP causes marked cytotoxicity via masking of a wide range of cellular surface molecules, including integrins. Considerable amounts of surface GP are shed from virus-infected cells in a soluble truncated form by tumor necrosis factor α-converting enzyme. In this study, the role of GP shedding was investigated using a reverse genetics approach by comparing recombinant viruses possessing amino acid substitutions at the GP shedding site. Virus with an L635V substitution showed a substantial decrease in shedding, whereas a D637V substitution resulted in a striking increase in the release of shed GP. Variations in shedding efficacy correlated with observed differences in the amounts of shed GP in the medium, GP present in virus-infected cells, and GP present on virions. An increase in shedding appeared to be associated with a reduction in viral cytotoxicity, and, vice versa, the virus that shed less was more cytotoxic. An increase in shedding also resulted in a reduction in viral infectivity, whereas a decrease in shedding efficacy enhanced viral growth characteristics in vitro. Differences in shedding efficacy and, as a result, differences in the amount of mature GP available for incorporation into budding virions did not equate to differences in overall release of viral particles. Likewise, data suggest that the resulting differences in the amount of mature GP on the cell surface led to variations in the GP content of released particles and, as a consequence, in infectivity. In conclusion, fine-tuning of the levels of EBOV GP expressed at the surface of virus-infected cells via GP shedding plays an important role in EBOV replication by orchestrating the balance between optimal virion GP content and cytotoxicity caused by GP. © The Author 2015. Published by Oxford University Press on behalf of the Infectious

  13. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies.

    Directory of Open Access Journals (Sweden)

    Anna Olivieri

    2011-12-01

    Full Text Available The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1 is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1, and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  14. Power System Stability Using Decentralized Under Frequency and Voltage Load Shedding

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Silva, Filipe Faria Da; Bak, Claus Leth

    2014-01-01

    information to shed the loads with higher voltage decay first. Therefore, this approach deals with coordination of voltage and frequency information instead of independent methods. Numerical simulations which are carried out in DigSilent PowerFactory software confirm the efficiency of proposed methodology...

  15. Prolonged Leptospira Urinary Shedding in a 10-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Emilie Chow

    2012-01-01

    Full Text Available We present a case of leptospirosis in a previously healthy girl following a trip to Costa Rica. While she was clinically asymptomatic, she had spirochetes cultured from her urine six weeks following her trip. Prolonged urinary shedding following infection with Leptospira is possible in humans and often has subtle manifestations in children.

  16. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    Science.gov (United States)

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

  17. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

  18. Synthetic sex pheromone attracts the leishmaniasis vector Lutzomyia longipalpis to experimental chicken sheds treated with insecticide

    Directory of Open Access Journals (Sweden)

    Brazil Reginaldo P

    2010-03-01

    Full Text Available Abstract Background Current strategies for controlling American visceral leishmaniasis (AVL have been unable to prevent the spread of the disease across Brazil. With no effective vaccine and culling of infected dogs an unpopular and unsuccessful alternative, new tools are urgently needed to manage populations of the sand fly vector, Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae. Here, we test two potential strategies for improving L. longipalpis control using the synthetic sand fly pheromone (±-9-methylgermacrene-B: the first in conjunction with spraying of animal houses with insecticide, the second using coloured sticky traps. Results Addition of synthetic pheromone resulted in greater numbers of male and female sand flies being caught and killed at experimental chicken sheds sprayed with insecticide, compared to pheromone-less controls. Furthermore, a ten-fold increase in the amount of sex pheromone released from test sheds increased the number of females attracted and subsequently killed. Treating sheds with insecticide alone resulted in a significant decrease in numbers of males attracted to sheds (compared to pre-spraying levels, and a near significant decrease in numbers of females. However, this effect was reversed through addition of synthetic pheromone at the time of insecticide spraying, leading to an increase in number of flies attracted post-treatment. In field trials of commercially available different coloured sticky traps, yellow traps caught more males than blue traps when placed in chicken sheds. In addition, yellow traps fitted with 10 pheromone lures caught significantly more males than pheromone-less controls. However, while female sand flies showed a preference for both blue and yellow pheromone traps sticky traps over white traps in the laboratory, neither colour caught significant numbers of females in chicken sheds, either with or without pheromone. Conclusions We conclude that synthetic pheromone could

  19. Identification of shed or plucked origin of Indian peafowl (Pavo cristatus) tail feathers: preliminary findings.

    Science.gov (United States)

    Sahajpal, Vivek; Goyal, S P

    2008-06-01

    Indian Peafowl (Pavo cristatus) tail covert feathers were studied to investigate the difference between shed and plucked feathers in the context of wildlife offence cases involving the killing of the Indian national bird for the purpose of plucking feathers. Plucked feathers were distinguished from shed feathers by examining their roots under low magnification of a stereoscopic microscope. A chemical test to show the presence of blood on the roots of plucked feathers was used to corroborate the plucked origin of feathers.

  20. Sanitation and Microbiological Quality in Production Field and Fruit-Packing Shed of Persimmon and Satsuma Mandarin in Japan

    Directory of Open Access Journals (Sweden)

    Hidemi Izumi

    2008-01-01

    Full Text Available The effects of sanitation treatments including chlorination (ca 10 ppm available chlorine of agricultural water and ethyl alcohol (70% spraying on packing shed equipment on microbial contamination on fruits and the environment were determined and compared with those in conventionally managed field and packing shed in persimmon and satsuma mandarin orchards. Chlorinated water reduced the microbial counts to levels below the lower limit of detection (1.4 log CFU/ml for bacteria and 2.0 log CFU/ml for fungi in most agricultural water samples. Microbial counts of pesticide solution, which contained the agricultural water or chlorinated water for the mixture, were lower in sanitary field than in control field in both fruit orchards. The number of bacterial and mold species detected in agricultural water, chlorinated water, and pesticide solution were almost proportional to microbial counts in each sample throughout the year. The chlorination treatment of agricultural water tended to reduce the counts of mesophiles and fungi on the peel of persimmon fruit during production season. The ethyl alcohol spray treatment on packing shed equipment resulted in a substantial microbial reduction on plastic harvest basket and container in persimmon orchard and plastic harvest basket and container, gloves, scissors, and size sorter in satsuma mandarin orchard. The spray application on packing shed equipment reduced the counts of mesophiles and fungi on the peel of persimmon fruit by >1 log CFU/g. The number of satsuma mandarin packing shed equipment containing the species found on fruit peel was higher in control than in sanitary packing shed. No human pathogens such as verotoxin-producing Escherichia coli and Salmonella were detected in any of the fruit and environmental samples. These results indicate that uses of sanitizers such as chlorine for agricultural water and ethyl alcohol for packing shed equipment would be useful in a good agricultural practices

  1. Sanitation and Microbiological Quality in Production Field and Fruit-Packing Shed of Persimmon and Satsuma Mandarin in Japan

    Directory of Open Access Journals (Sweden)

    Hidemi Izumi

    2008-01-01

    Full Text Available The effects of sanitation treatments including chlorination (ca 10 ppm available chlorine of agricultural water and ethyl alcohol (70% spraying on packing shed equipment on microbial contamination on fruits and the environment were determined and compared with those in conventionally managed field and packing shed in persimmon and satsuma mandarin orchards. Chlorinated water reduced the microbial counts to levels below the lower limit of detection (1.4 log CFU/ml for bacteria and 2.0 log CFU/ml for fungi in most agricultural water samples. Microbial counts of pesticide solution, which contained the agricultural water or chlorinated water for the mixture, were lower in sanitary field than in control field in both fruit orchards. The number of bacterial and mold species detected in agricultural water, chlorinated water, and pesticide solution were almost proportional to microbial counts in each sample throughout the year. The chlorination treatment of agricultural water tended to reduce the counts of mesophiles and fungi on the peel of persimmon fruit during production season. The ethyl alcohol spray treatment on packing shed equipment resulted in a substantial microbial reduction on plastic harvest basket and container in persimmon orchard and plastic harvest basket and container, gloves, scissors, and size sorter in satsuma mandarin orchard. The spray application on packing shed equipment reduced the counts of mesophiles and fungi on the peel of persimmon fruit by 1 log CFU/g. The number of satsuma mandarin packing shed equipment containing the species found on fruit peel was higher in control than in sanitary packing shed. No human pathogens such as verotoxin-producing Escherichia coli and Salmonella were detected in any of the fruit and environmental samples. These results indicate that uses of sanitizers such as chlorine for agricultural water and ethyl alcohol for packing shed equipment would be useful in a good agricultural practices

  2. SHEDS-HT: an integrated probabilistic exposure model for prioritizing exposures to chemicals with near-field and dietary sources.

    Science.gov (United States)

    Isaacs, Kristin K; Glen, W Graham; Egeghy, Peter; Goldsmith, Michael-Rock; Smith, Luther; Vallero, Daniel; Brooks, Raina; Grulke, Christopher M; Özkaynak, Halûk

    2014-11-04

    United States Environmental Protection Agency (USEPA) researchers are developing a strategy for high-throughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologically relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. Based on probabilistic methods and algorithms developed for The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals (SHEDS-MM), a new mechanistic modeling approach has been developed to accommodate high-throughput (HT) assessment of exposure potential. In this SHEDS-HT model, the residential and dietary modules of SHEDS-MM have been operationally modified to reduce the user burden, input data demands, and run times of the higher-tier model, while maintaining critical features and inputs that influence exposure. The model has been implemented in R; the modeling framework links chemicals to consumer product categories or food groups (and thus exposure scenarios) to predict HT exposures and intake doses. Initially, SHEDS-HT has been applied to 2507 organic chemicals associated with consumer products and agricultural pesticides. These evaluations employ data from recent USEPA efforts to characterize usage (prevalence, frequency, and magnitude), chemical composition, and exposure scenarios for a wide range of consumer products. In modeling indirect exposures from near-field sources, SHEDS-HT employs a fugacity-based module to estimate concentrations in indoor environmental media. The concentration estimates, along with relevant exposure factors and human activity data, are then used by the model to rapidly generate probabilistic population distributions of near-field indirect exposures via dermal, nondietary ingestion, and inhalation pathways. Pathway-specific estimates of near-field direct exposures from consumer products are also modeled

  3. Epidemiology of Chronic Wasting Disease: PrPres Detection, Shedding and Environmental Contamination

    National Research Council Canada - National Science Library

    Lewis, Randolph V

    2005-01-01

    .... The specific goals of these studies are to develop sensitive assays for PrP(exp res) as a marker for infectivity, and use these techniques to monitor the dynamics and modes of shedding of PrP(exp res...

  4. Leading-edge vortex shedding from rotating wings

    Energy Technology Data Exchange (ETDEWEB)

    Kolomenskiy, Dmitry [Centre de Recherches Mathématiques (CRM), Department of Mathematics and Statistics, McGill University, 805 Sherbrooke W., Montreal, QC H3A 0B9 (Canada); Elimelech, Yossef [Faculty of Aerospace Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Schneider, Kai, E-mail: dkolom@gmail.com [M2P2–CNRS, Université d' Aix-Marseille, 39, rue Frédéric Joliot-Curie, F-13453 Marseille Cedex 13 (France)

    2014-06-01

    This paper presents a numerical investigation of the leading-edge vortices generated by rotating triangular wings at Reynolds number Re = 250. A series of three-dimensional numerical simulations have been carried out using a Fourier pseudo-spectral method with volume penalization. The transition from stable attachment of the leading-edge vortex to periodic vortex shedding is explored, as a function of the wing aspect ratio and the angle of attack. It is found that, in a stable configuration, the spanwise flow in the recirculation bubble past the wing is due to the centrifugal force, incompressibility and viscous stresses. For the flow outside of the bubble, an inviscid model of spanwise flow is presented. (papers)

  5. Hjemløshed i Grønland

    DEFF Research Database (Denmark)

    Hansen, Knud Erik; Andersen, Hans Thor

    Rapporten giver en beskrivelse af karakteren af hjemløsheden i Grønland. Den beskriver forholdene for tre måder at være ude i hjemløshed på i Grønland, hvordan husstande når dertil og hvilke muligheder de har for at komme ud af hjemløsheden. I rapporten indgår beskrivelser af en række personers liv...... households get homeless and their options to get out of homelessness. The report contains descriptions of how a number of people live in homelessness. The three types are: Homeless with no fixed accommodation, resettled living in resettlement housing and homeless who are long-time living with family, friends...

  6. Mucosal HSV-2 specific CD8+ T-cells represent containment of prior viral shedding rather than a correlate of future protection

    Directory of Open Access Journals (Sweden)

    Joshua Tisdell Schiffer

    2013-07-01

    Full Text Available It is largely unknown why certain infected hosts shed Herpes Simplex Virus-2 (HSV-2 more frequently and have more severe disease manifestations than others. One idea is that different density or functional capacity of tissue resident effector memory CD8+ T-cells between infected persons may explain phenotypic variability. To generate hypotheses for contrasting shedding patterns in different infected hosts, a spatial mathematical model was employed to evaluate the effects of variability in tissue resident effector memory CD8+ T-cell response, and HSV-2 replication and spread, on viral shedding rate. Model simulations suggest that high levels of CD8+ T-cells in the mucosa do not necessarily indicate a protective phenotype but rather an effective response to recent shedding. Moreover, higher CD8+ T-cell expansion rate and lower viral replication rate, which correlate with better short-term control, may have only a minor impact on long term shedding rates. Breakthrough shedding occurs under all sets of model parameter assumptions, because CD8+ T-cell levels only surpass a protective threshold in a minority of genital tract mucosal micro-regions. If CD8+ T-cell levels are artificially increased using an immunotherapeutic approach, better control of shedding is predicted to occur for at least a year. These results highlight the complex co-dependent relationship between HSV-2 and tissue resident CD8+ lymphocytes during the course of natural infection.

  7. Vortex Shedding from Tapered Cylinders at high Reynolds Numbers

    DEFF Research Database (Denmark)

    Johansson, Jens; Andersen, Michael Styrk; Christensen, Silas Sverre

    2015-01-01

    percent for strakes of circular cross section. The present paper argues that this height can be reduced for structures where the critical wind velocity for vortex shedding is in the Supercritical Reynolds number regime. The present investigations are aimed for suppressing VIV on offshore wind turbine......^5 (Supercritical). Results indicate that circular strakes with a diameter corresponding to 3 percent of the structures mean diameter can be used to efficiently reduce VIV in the Supercritical Reynolds number regime....

  8. Quantification of eDNA shedding rates from invasive bighead carp Hypophthalmichthys nobilis and silver carp Hypophthalmichthys molitrix

    Science.gov (United States)

    Klymus, Katy E.; Richter, Catherine A.; Chapman, Duane C.; Paukert, Craig P.

    2015-01-01

    Wildlife managers can more easily mitigate the effects of invasive species if action takes place before a population becomes established. Such early detection requires sensitive survey tools that can detect low numbers of individuals. Due to their high sensitivity, environmental DNA (eDNA) surveys hold promise as an early detection method for aquatic invasive species. Quantification of eDNA amounts may also provide data on species abundance and timing of an organism’s presence, allowing managers to successfully combat the spread of ecologically damaging species. To better understand the link between eDNA and an organism’s presence, it is crucial to know how eDNA is shed into the environment. Our study used quantitative PCR (qPCR) and controlled laboratory experiments to measure the amount of eDNA that two species of invasive bigheaded carps (Hypophthalmichthys nobilis and Hypophthalmichthys molitrix) shed into the water. We first measured how much eDNA a single fish sheds and the variability of these measurements. Then, in a series of manipulative lab experiments, we studied how temperature, biomass (grams of fish), and diet affect the shedding rate of eDNA by these fish. We found that eDNA amounts exhibit a positive relationship with fish biomass, and that feeding could increase the amount of eDNA shed by ten-fold, whereas water temperature did not have an effect. Our results demonstrate that quantification of eDNA may be useful for predicting carp density, as well as densities of other rare or invasive species.

  9. Herpes simplex virus-2 genital tract shedding is not predictable over months or years in infected persons.

    Directory of Open Access Journals (Sweden)

    Varsha Dhankani

    2014-11-01

    Full Text Available Herpes simplex virus-2 (HSV-2 is a chronic reactivating infection that leads to recurrent shedding episodes in the genital tract. A minority of episodes are prolonged, and associated with development of painful ulcers. However, currently, available tools poorly predict viral trajectories and timing of reactivations in infected individuals. We employed principal components analysis (PCA and singular value decomposition (SVD to interpret HSV-2 genital tract shedding time series data, as well as simulation output from a stochastic spatial mathematical model. Empirical and model-derived, time-series data gathered over >30 days consists of multiple complex episodes that could not be reduced to a manageable number of descriptive features with PCA and SVD. However, single HSV-2 shedding episodes, even those with prolonged duration and complex morphologies consisting of multiple erratic peaks, were consistently described using a maximum of four dominant features. Modeled and clinical episodes had equivalent distributions of dominant features, implying similar dynamics in real and simulated episodes. We applied linear discriminant analysis (LDA to simulation output and identified that local immune cell density at the viral reactivation site had a predictive effect on episode duration, though longer term shedding suggested chaotic dynamics and could not be predicted based on spatial patterns of immune cell density. These findings suggest that HSV-2 shedding patterns within an individual are impossible to predict over weeks or months, and that even highly complex single HSV-2 episodes can only be partially predicted based on spatial distribution of immune cell density.

  10. Causes and implications of the correlation between forest productivity and tree mortality rates

    Science.gov (United States)

    Stephenson, Nathan L.; van Mantgem, Philip J.; Bunn, Andrew G.; Bruner, Howard; Harmon, Mark E.; O'Connell, Kari B.; Urban, Dean L.; Franklin, Jerry F.

    2011-01-01

    At global and regional scales, tree mortality rates are positively correlated with forest net primary productivity (NPP). Yet causes of the correlation are unknown, in spite of potentially profound implications for our understanding of environmental controls of forest structure and dynamics and, more generally, our understanding of broad-scale environmental controls of population dynamics and ecosystem processes. Here we seek to shed light on the causes of geographic patterns in tree mortality rates, and we consider some implications of the positive correlation between mortality rates and NPP. To reach these ends, we present seven hypotheses potentially explaining the correlation, develop an approach to help distinguish among the hypotheses, and apply the approach in a case study comparing a tropical and temperate forest.

  11. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

    Science.gov (United States)

    Ogimi, Chikara; Greninger, Alexander L; Waghmare, Alpana A; Kuypers, Jane M; Shean, Ryan C; Xie, Hu; Leisenring, Wendy M; Stevens-Ayers, Terry L; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-07-15

    Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of Genome changes were consistent with the expected molecular clock of HCoV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Measurement on the cavitating vortex shedding behind rectangular obstacles

    International Nuclear Information System (INIS)

    Hegedus, F; Hos, C; Pandula, Z; Kullmann, L

    2010-01-01

    Measurement results on the cavitating vortex shedding behind sharp-edged rectangular bodies are presented, intended to provide benchmark cases for the validation of unsteady cavitation models of CFD codes. Rectangular bodies of increasing aspect ratio (1, 2, 3 and 4) were used with a constant 25mm height (12.5% blockage ratio). The water velocity in the 0.2x0.05m test section of the channel was varied between 1 and 12 m/s resulting in a Reynolds number in the range of (0.4-3.5)x105. Pressure signals were measured at several locations, notably in the wake. Dominant frequencies and Strouhal numbers are reported from cavitation-free flow (classic von Karman vortex shedding) up to supercavitation as a function of the free-stream Reynolds number. The results are in good agreement with the literature in case of the square cylinder. We experienced a slight increase of the dominant Strouhal number with increasing aspect ratio. This result is somewhat inconsistent with the literature, in which a fall of the Strouhal number can be observed at side ratio 2. This may be the consequence of the different ranges of Reynolds numbers. It was also found that between the inception of cavitation and the formation of supercavitation the Strouhal number is not affected by cavitation.

  13. Measurement on the cavitating vortex shedding behind rectangular obstacles

    Energy Technology Data Exchange (ETDEWEB)

    Hegedus, F; Hos, C; Pandula, Z; Kullmann, L, E-mail: hegedusf@hds.bme.h [Department of Hydrodynamic Systems, Budapest University of Technology and Economics Muegyetem rkp. 1, Budapest 1111 (Hungary)

    2010-08-15

    Measurement results on the cavitating vortex shedding behind sharp-edged rectangular bodies are presented, intended to provide benchmark cases for the validation of unsteady cavitation models of CFD codes. Rectangular bodies of increasing aspect ratio (1, 2, 3 and 4) were used with a constant 25mm height (12.5% blockage ratio). The water velocity in the 0.2x0.05m test section of the channel was varied between 1 and 12 m/s resulting in a Reynolds number in the range of (0.4-3.5)x105. Pressure signals were measured at several locations, notably in the wake. Dominant frequencies and Strouhal numbers are reported from cavitation-free flow (classic von Karman vortex shedding) up to supercavitation as a function of the free-stream Reynolds number. The results are in good agreement with the literature in case of the square cylinder. We experienced a slight increase of the dominant Strouhal number with increasing aspect ratio. This result is somewhat inconsistent with the literature, in which a fall of the Strouhal number can be observed at side ratio 2. This may be the consequence of the different ranges of Reynolds numbers. It was also found that between the inception of cavitation and the formation of supercavitation the Strouhal number is not affected by cavitation.

  14. Control of a coupled map lattice model for vortex shedding in the ...

    Indian Academy of Sciences (India)

    The DNL method was found to be the most efficient controller of the low-order CML model. The .... these techniques to the vortex shedding process using CML models is an additional moti- ..... near the cable vibration nodes (figure 3a). Vortex ...

  15. Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.

    Science.gov (United States)

    Bender Ignacio, Rachel A; Perti, Tara; Magaret, Amalia S; Rajagopal, Sharanya; Stevens, Claire E; Huang, Meei-Li; Selke, Stacy; Johnston, Christine; Marrazzo, Jeanne; Wald, Anna

    2015-12-15

    Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear. We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates. 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL. Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions. NCT01448616. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Boundary layer effects on the vortex shedding in a Donaldson- type hydrofoil

    International Nuclear Information System (INIS)

    Fontanals, A; Guardo, A; Egusquiza, E; Zobeiri, A; Farhat, M; Avellan, F

    2014-01-01

    Fluid - Structure Interaction (FSI) phenomena is becoming a relevant study field for the design or revamping of hydropower plants. The generalized trend of increasing flow rates and reducing rotor blades/stay vanes thickness in order to improve the efficiency of the machine together with a major push from plant owners/operators for production flexibility (partial load operation is more common nowadays) make the FSI between the vortex shedding phenomenon and the vanes/blades of the machine an area of interest. From a design point of view, the machine structure has to resist all the hydrodynamic forces generated and maintain tension stresses under the fatigue limit to ensure a machine lifetime of several decades. To accomplish that goal, designers have to assure there is no presence of strong coupling phenomena (lock-in) between the vortex shedding frequency and the eigenfrequencies of the structure. As the vortex street is directly related to the state of the boundary layer along the hydrofoil, in this paper the effect of the boundary layer on the vortex shedding in a Donaldson-type hydrofoil is studied using Computational Fluid Dynamics (CFD). The development of the boundary layer along the Donaldson trailing edge hydrofoil chord is presented under lock-off conditions. The results are validated against previously obtained experimental results. Since the Donaldson trailing edge is non-symmetric, the boundary layer velocity profiles are reported for the suction and pressure side of the hydrofoil. In addition, the effect of the Donaldson trailing edge on laminar-to-turbulent transition on both sides of the hydrofoil is studied

  17. Cancerous epithelial cell lines shed extracellular vesicles with a bimodal size distribution that is sensitive to glutamine inhibition

    International Nuclear Information System (INIS)

    Santana, Steven Michael; Kirby, Brian J; Antonyak, Marc A; Cerione, Richard A

    2014-01-01

    Extracellular shed vesicles (ESVs) facilitate a unique mode of cell–cell communication wherein vesicle uptake can induce a change in the recipient cell's state. Despite the intensity of ESV research, currently reported data represent the bulk characterization of concentrated vesicle samples with little attention paid to heterogeneity. ESV populations likely represent diversity in mechanisms of formation, cargo and size. To better understand ESV subpopulations and the signaling cascades implicated in their formation, we characterize ESV size distributions to identify subpopulations in normal and cancerous epithelial cells. We have discovered that cancer cells exhibit bimodal ESV distributions, one small-diameter and another large-diameter population, suggesting that two mechanisms may govern ESV formation, an exosome population and a cancer-specific microvesicle population. Altered glutamine metabolism in cancer is thought to fuel cancer growth but may also support metastatic niche formation through microvesicle production. We describe the role of a glutaminase inhibitor, compound 968, in ESV production. We have discovered that inhibiting glutamine metabolism significantly impairs large-diameter microvesicle production in cancer cells. (paper)

  18. Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding

    Directory of Open Access Journals (Sweden)

    Han Wu

    2018-01-01

    Full Text Available Dysfunction of endothelial progenitor cells (EPCs contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4, a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.

  19. Shedding light on solar technologies-A techno-economic assessment and its policy implications

    International Nuclear Information System (INIS)

    Peters, Michael; Schmidt, Tobias S.; Wiederkehr, David; Schneider, Malte

    2011-01-01

    Solar power technologies will have to become a major pillar in the world's future energy system to combat climate change and resource depletion. However, it is unclear which solar technology is and will prove most viable. Therefore, a comprehensive comparative assessment of solar technologies along the key quantitative and qualitative competitiveness criteria is needed. Based on a literature review and detailed techno-economic modeling for 2010 and 2020 in five locations, we provide such an assessment for the three currently leading large-scale solar technologies. We show that today these technologies cannot yet compete with conventional forms of power generation but approach competitiveness around 2020 in favorable locations. Furthermore, from a global perspective we find that none of the solar technologies emerges as a clear winner and that cost of storing energy differs by technology and can change the order of competitiveness in some instances. Importantly, the competitiveness of the different technologies varies considerably across locations due to differences in, e.g., solar resource and discount rates. Based on this analysis, we discuss policy implications with regard to fostering the diffusion of solar technologies while increasing the efficiency of policy support through an adequate geographical allocation of solar technologies. - Highlights: → We conduct a comprehensive comparative assessment of solar technologies (CSP/PV). → While solar technologies approach competitiveness in 2020, no clear winner emerges. → Solar resource and discount rate heavily impact competitiveness of solar technologies. → Adequate geographical allocation of solar technologies increases policy efficiency. → Focus on key cost down levers and strategic co-benefits of solar technologies needed.

  20. Long-term viremia and fecal shedding in pups after modified-live canine parvovirus vaccination.

    Science.gov (United States)

    Decaro, Nicola; Crescenzo, Giuseppe; Desario, Costantina; Cavalli, Alessandra; Losurdo, Michele; Colaianni, Maria Loredana; Ventrella, Gianpiero; Rizzi, Stefania; Aulicino, Stefano; Lucente, Maria Stella; Buonavoglia, Canio

    2014-06-24

    Canine parvovirus (CPV) modified live virus vaccines are able to infect vaccinated dogs replicating in the bloodstream and enteric mucosa. However, the exact duration and extent of CPV vaccine-induced viremia and fecal shedding are not known. With the aim to fill this gap, 26 dogs were administered two commercial vaccines containing a CPV-2 or CPV-2b strain and monitored for 28 days after vaccination. By using real-time PCR, vaccine-induced viremia and shedding were found to be long lasting for both vaccinal strains. Vaccinal CPV-2b shedding was detected for a shorter period than CPV-2 (12 against 19 mean days) but with greater viral loads, whereas viremia occurred for a longer period (22 against 19 mean days) and with higher titers for CPV-2b. Seroconversion appeared as early as 7 and 14 days post-vaccination for CPV-2b and CPV-2 vaccines, respectively. With no vaccine there was any diagnostic interference using in-clinic or hemagglutination test, since positive results were obtained only by fecal real-time PCR testing. The present study adds new insights into the CPV vaccine persistence in the organism and possible interference with diagnostic tests. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Longitudinal prevalence and faecal shedding of Chlamydia pecorum in sheep.

    Science.gov (United States)

    Yang, Rongchang; Jacobson, Caroline; Gardner, Graham; Carmichael, Ian; Campbell, Angus J D; Ryan, Una

    2014-09-01

    The prevalence and faecal shedding of Chlamydia spp. in sheep in Australia has not been well described. Two species-specific quantitative PCRs (qPCRs) targeting the chlamydial outer membrane protein cell surface antigen gene (ompA) were validated and used to determine the prevalence and faecal shedding of C. abortus and C. pecorum from faecal samples of lambs at three sampling times (weaning, post-weaning and pre-slaughter) from eight farms in South Australia, New South Wales, Victoria and Western Australia. A total of 3412 faecal samples were collected and screened from approximately 1189 lambs across the four states. C. abortus was not detected in any of the samples screened. The overall prevalence of C. pecorum was 1027/3412 (30.1%) and median bacterial concentrations at weaning, post-weaning and pre-slaughter were 1.8 × 10(7), 1.2 × 10(7) and 9.6 × 10(5)/g faeces, respectively. A subset of C. pecorum positive samples from each farm, (n = 48) was sequenced to confirm their identity. The present study demonstrates that C. pecorum is prevalent in Australian sheep, highlighting a need for further research on the impact of this bacterium on production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. rROP2 from Toxoplasma gondii as a potential vaccine against oocyst shedding in domestic cats

    Directory of Open Access Journals (Sweden)

    Dauton Luiz Zulpo

    Full Text Available Abstract The aim of the present study was to evaluate oocyst shedding in cats immunized by nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus were divided in three groups G1, G2 and G3 (n=4. Animals from G1 received 100 μg of rROP2 proteins plus 20 μg of Quil-A, G2 received 100 μg of BSA plus 20 μg of Quil-A, and the G3 only saline solution (control group. All treatments were done by intranasal route at days 0, 21, 42, and 63. The challenge was performed in all groups on day 70 with ≅ 800 tissue cysts of ME-49 strain by oral route. Animals from G1 shed less oocysts (86.7% than control groups. ELISA was used to detect anti-rROP2 IgG and IgA, however, there were no correlation between number of oocyst shedding by either IgG or IgA antibody levels. In the present work, in spite of lesser oocysts production in immunized group than control groups, it was not possible to associate the use of rROP2 via nostrils with protection against oocyst shedding. For the future, the use of either other recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to try improving the efficacy of this kind of vaccine.

  3. Molecular identification of a malaria merozoite surface sheddase.

    Directory of Open Access Journals (Sweden)

    Philippa K Harris

    2005-11-01

    Full Text Available Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface "sheddase," but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase. We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite.

  4. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Directory of Open Access Journals (Sweden)

    Jim Todd

    Full Text Available To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1 57 women at 70 clinic visits with clinical genital herpes; (2 39 of the same women at 46 clinic visits when asymptomatic; (3 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL, herpetic lesions, HSV shedding and other factors were examined.Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03. In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001 and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001 but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27.HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  5. Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures

    Science.gov (United States)

    Desmarets, Lowiese M. B.; Vermeulen, Ben L.; Theuns, Sebastiaan; Conceição-Neto, Nádia; Zeller, Mark; Roukaerts, Inge D. M.; Acar, Delphine D.; Olyslaegers, Dominique A. J.; Van Ranst, Marc; Matthijnssens, Jelle; Nauwynck, Hans J.

    2016-01-01

    Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28–56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8+ regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise. PMID:26822958

  6. Role of EGFR transactivation in preventing apoptosis in Pseudomonas aeruginosa-infected human corneal epithelial cells.

    Science.gov (United States)

    Zhang, Jing; Li, Hui; Wang, Jinzhao; Dong, Zheng; Mian, Shahzad; Yu, Fu-Shin X

    2004-08-01

    To determine the role of epidermal growth factor (EGF) receptor (EGFR)-mediated signaling pathways in preventing infection-induced apoptosis in human corneal epithelial cells (HCECs). Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG1478, the extracellular signal-regulated kinase (ERK) inhibitor U0126, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, the heparin-binding EGF-like growth factor (HB-EGF) antagonist CRM197, the HB-EGF neutralizing antibody, or the matrix metalloproteinase inhibitor GM6001. The activation of EGFR was analyzed by immunoprecipitation using EGFR antibodies, followed by Western blot analysis with phosphotyrosine antibody. Phosphorylation of ERK and Akt, a major substrate of PI3K, and generation of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) were determined by Western blot analysis. Apoptotic cells were characterized by positive staining of active caspase-3, loss of mitochondrial cytochrome c, and condensation of chromosomes. Apoptosis was also confirmed by measuring caspase-3 activity and assessing the generation of cleaved caspase-3 and PARP. P. aeruginosa infection of HUCL cells resulted in EGFR activation and EGFR-dependent ERK1/2 and PI3K phosphorylation. Inhibition of EGFR, ERK1/2, and PI3K activities with kinase-specific inhibitors (AG1478, U0126, and LY294002, respectively) resulted in an increase in the number of apoptotic cells, in elevated cellular caspase-3 activity, and/or in increased cleaved PARP in P. aeruginosa-infected HUCL cells or primary culture of HCECs. Blocking HB-EGF ectodomain shedding by inhibition of matrix metalloproteinase-mediated proteolysis, downregulation of HB-EGF, or neutralization of its activity retarded infection-induced EGFR transactivation and, as a consequence, increased infection-induced HUCL apoptosis. Bacterial infection of HCECs induces

  7. Role of EGFR Transactivation in Preventing Apoptosis in Pseudomonas aeruginosa–Infected Human Corneal Epithelial Cells

    Science.gov (United States)

    Zhang, Jing; Li, Hui; Wang, Jinzhao; Dong, Zheng; Mian, Shahzad; Yu, Fu-Shin X.

    2009-01-01

    PURPOSE To determine the role of epidermal growth factor (EGF) receptor (EGFR)–mediated signaling pathways in preventing infection-induced apoptosis in human corneal epithelial cells (HCECs). METHODS Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG1478, the extracellular signal-regulated kinase (ERK) inhibitor U0126, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, the heparin-binding EGF-like growth factor (HB-EGF) antagonist CRM197, the HB-EGF neutralizing antibody, or the matrix metalloproteinase inhibitor GM6001. The activation of EGFR was analyzed by immunoprecipitation using EGFR antibodies, followed by Western blot analysis with phosphotyrosine antibody. Phosphorylation of ERK and Akt, a major substrate of PI3K, and generation of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) were determined by Western blot analysis. Apoptotic cells were characterized by positive staining of active caspase-3, loss of mitochondrial cytochrome c, and condensation of chromosomes. Apoptosis was also confirmed by measuring caspase-3 activity and assessing the generation of cleaved caspase-3 and PARP. RESULTS P. aeruginosa infection of HUCL cells resulted in EGFR activation and EGFR-dependent ERK1/2 and PI3K phosphorylation. Inhibition of EGFR, ERK1/2, and PI3K activities with kinase-specific inhibitors (AG1478, U0126, and LY294002, respectively) resulted in an increase in the number of apoptotic cells, in elevated cellular caspase-3 activity, and/or in increased cleaved PARP in P. aeruginosa–infected HUCL cells or primary culture of HCECs. Blocking HB-EGF ectodomain shedding by inhibition of matrix metalloproteinase–mediated proteolysis, downregulation of HB-EGF, or neutralization of its activity retarded infection-induced EGFR transactivation and, as a consequence, increased infection-induced HUCL apoptosis

  8. Epidemiology of Chronic Wasting Disease: PrP(res) Detection, Shedding, and Environmental Contamination

    National Research Council Canada - National Science Library

    Williams, Elizabeth S; Miller, Michael W; Lewis, Randolf V; Raisbeck, Merl F; Cook, Walter W

    2004-01-01

    .... The specific goals of these studies are to develop sensitive as says for PrP(exp res) as a marker for infectivity, and use these techniques to monitor the dynamics and modes of shedding of PrP(exp res...

  9. Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant

    Directory of Open Access Journals (Sweden)

    Karin Kosulin

    2018-02-01

    Full Text Available Human adenoviruses (HAdV are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%, and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p < 0.01. In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p < 0.0001. The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.

  10. Relational Human Rights: Shed-DNA and the Identification of the Living Disappeared

    DEFF Research Database (Denmark)

    Vaisman, Noa

    2014-01-01

    forcibly abducted by the last military dictatorship in Argentina. They were raised by the perpetrators of the crime or their accomplices and kept unaware of their birth origins. TheCourt's deliberations focused on Guillermo's appeal of a lower-court decision to carry out an identity test based on his shed...

  11. Root cause analysis of oxide scale forming and shedding in high temperature reheater of a 200MW super high pressure boiler

    Science.gov (United States)

    Bo, Jiang; Hao, Weidong; Hu, Zhihong; Liu, Fuguo

    2015-12-01

    In order to solve the problem of over temperature tube-burst caused by oxide scale shedding and blocking tubes of high temperature reheater of a 200MW super high pressure power plant boiler, this paper expounds the mechanism of scale forming and shedding, and analyzes the probable causes of the tube-burst failure. The results show that the root cause of scale forming is that greater steam extraction flow after reforming of the second extraction leads to less steam flow into reheater, which causes over temperature to some of the heated tubes; and the root cause of scale shedding is that long term operation in AGC-R mode brings about great fluctuations of unit load, steam temperature and pressure, accelerating scale shedding. In conclusion, preventive measures are drawn up considering the operation mode of the unit.

  12. Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)*

    Science.gov (United States)

    Lu, Zhuoyang; Reddy, M. V. V. V. Sekhar; Liu, Jianfang; Kalichava, Ana; Liu, Jiankang; Zhang, Lei; Chen, Fang; Wang, Yun; Holthauzen, Luis Marcelo F.; White, Mark A.; Seshadrinathan, Suchithra; Zhong, Xiaoying; Ren, Gang; Rudenko, Gabby

    2016-01-01

    Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule. PMID:27621318

  13. Information report published in application of the article 145 of the rule by the Commission on economic affairs on stakes and impacts of distributed load shedding. Nr 3690

    International Nuclear Information System (INIS)

    Battistel, Marie-Noelle

    2016-01-01

    Distributed load shedding is a complex issue with actual stakes for public policy: a constrained context for public finances, and necessity to use public money in an optimal and efficient way. Even though load shedding has a positive impact on the environment, its business model presents important weaknesses and cannot survive without public subsidy. This report addresses these issues, and first defines load shedding, states the reasons for supporting distributed load shedding, discusses how the French arrangement for the valorisation of load shedding is ambitious and innovative. It also outlines and discusses the present difficulties faced by load shedding, that it could become in the future an actual lever for energy transition. The authors then examine what public authorities could do regarding the payment of load shedding by the operator to the provider, regarding returns on experience and other solutions on the short term, and regarding the promotion of innovative means of distributed load shedding which would be focused on consumers

  14. An effective Load shedding technique for micro-grids using artificial neural network and adaptive neuro-fuzzy inference system

    Directory of Open Access Journals (Sweden)

    Foday Conteh

    2017-09-01

    Full Text Available In recent years, the use of renewable energy sources in micro-grids has become an effectivemeans of power decentralization especially in remote areas where the extension of the main power gridis an impediment. Despite the huge deposit of natural resources in Africa, the continent still remains inenergy poverty. Majority of the African countries could not meet the electricity demand of their people.Therefore, the power system is prone to frequent black out as a result of either excess load to the systemor generation failure. The imbalance of power generation and load demand has been a major factor inmaintaining the stability of the power systems and is usually responsible for the under frequency andunder voltage in power systems. Currently, load shedding is the most widely used method to balancebetween load and demand in order to prevent the system from collapsing. But the conventional methodof under frequency or under voltage load shedding faces many challenges and may not perform asexpected. This may lead to over shedding or under shedding, causing system blackout or equipmentdamage. To prevent system cascade or equipment damage, appropriate amount of load must beintentionally and automatically curtailed during instability. In this paper, an effective load sheddingtechnique for micro-grids using artificial neural network and adaptive neuro-fuzzy inference system isproposed. The combined techniques take into account the actual system state and the exact amount ofload needs to be curtailed at a faster rate as compared to the conventional method. Also, this methodis able to carry out optimal load shedding for any input range other than the trained data. Simulationresults obtained from this work, corroborate the merit of this algorithm.

  15. Comparative community-level associations of helminth infections and microparasite shedding in wild long-tailed macaques in Bali, Indonesia.

    Science.gov (United States)

    Wilcox, Justin J S; Lane-Degraaf, Kelly E; Fuentes, Agustin; Hollocher, Hope

    2015-03-01

    Helminthes have the capacity to modulate host immunity, leading to positive interactions with coinfecting microparasites. This phenomenon has been primarily studied during coinfections with a narrow range of geo-helminthes and intracellular microparasites in human populations or under laboratory conditions. Far less is known regarding differences in coinfection dynamics between helminth types, the range of microparasites that might be affected or the overall community-level effects of helminth infections on microparasites in wild systems. Here, we analysed the presence/absence and abundance patterns of enteric parasites in long-tailed macaques (Macaca fascicularis) on the island of Bali, Indonesia, to assess whether naturally occurring helminth infections were associated with increased shedding of the most common intracellular (Cryptosporidium spp., Isospora spp.) and extracellular (Entamoeba spp., Giardia spp.) microparasites. We also comparatively assessed the statistical correlations of different helminth taxa with microparasite shedding to determine if there were consistent relationships between the specific helminth taxa and microparasites. Helminth infections were associated with increased shedding of both intracellular and extracellular microparasites. Platyhelminthes repeatedly displayed strong positive correlations with several microparasites; while nematodes did not. Our results indicate that helminthes can influence microparasite community shedding dynamics under wild conditions, but that trends may be driven by a narrow range of helminthes.

  16. Housing a Raspberry Pi Connected AS-1 Seismometer in a Solar-Paneled Shed

    Science.gov (United States)

    Marton, F.; Tokman, T. L.; Echreshzadeh, M.; Palaric, K. D.; Filippone, N. V.; Sivo, J.

    2016-12-01

    Last year, students working on the SeismoSTEM project at Bergen Community College successfully manufactured and assembled an AS-1 seismometer1. However, issues students encountered were not knowing where to place the TC-1 and AS-1 seismometers, nor how to configure the instruments with a computer for monitoring and measuring earthquakes. Our solution was to purchase a Raspberry Pi 3 model B, which has four USB ports and a Wi-Fi adapter. We then installed the Raspbian operating system that can run jAmaSeis, which allows for the collection and analysis of seismic data. In terms of the shed that was constructed last summer2, we installed roof shingles, as well as a ventilation system to prevent overheating. The seismometers will then be placed on a concrete slab. In the future, we plan on applying a wood varnish around the exterior of the shed, as well as gravel around the shed for water drainage as well as to make it more visually appealing. Moreover, we plan on mounting a 170-W solar panel on the roof to charge a 12-V deep cycle marine battery, which will provide electricity to the system. References: 1Tokman, T.L. et al., What's shaking? Manufacturing & assembling an AS-1 educational seismometer for undergraduate stem research, Geological Society of America Abstracts with Programs. Vol. 47, No. 7, p.524, 2015. 2Palaric, K.D., et al., Constructing a solar-powered seismic station for educational seismometers, Geological Society of America Abstracts with Programs. Vol. 47, No. 7, p.524, 2015.

  17. Adjoint sensitivity studies of loop current and eddy shedding in the Gulf of Mexico

    KAUST Repository

    Gopalakrishnan, Ganesh; Cornuelle, Bruce D.; Hoteit, Ibrahim

    2013-01-01

    Adjoint model sensitivity analyses were applied for the loop current (LC) and its eddy shedding in the Gulf of Mexico (GoM) using the MIT general circulation model (MITgcm). The circulation in the GoM is mainly driven by the energetic LC and subsequent LC eddy separation. In order to understand which ocean regions and features control the evolution of the LC, including anticyclonic warm-core eddy shedding in the GoM, forward and adjoint sensitivities with respect to previous model state and atmospheric forcing were computed using the MITgcm and its adjoint. Since the validity of the adjoint model sensitivities depends on the capability of the forward model to simulate the real LC system and the eddy shedding processes, a 5 year (2004–2008) forward model simulation was performed for the GoM using realistic atmospheric forcing, initial, and boundary conditions. This forward model simulation was compared to satellite measurements of sea-surface height (SSH) and sea-surface temperature (SST), and observed transport variability. Despite realistic mean state, standard deviations, and LC eddy shedding period, the simulated LC extension shows less variability and more regularity than the observations. However, the model is suitable for studying the LC system and can be utilized for examining the ocean influences leading to a simple, and hopefully generic LC eddy separation in the GoM. The adjoint sensitivities of the LC show influences from the Yucatan Channel (YC) flow and Loop Current Frontal Eddy (LCFE) on both LC extension and eddy separation, as suggested by earlier work. Some of the processes that control LC extension after eddy separation differ from those controlling eddy shedding, but include YC through-flow. The sensitivity remains stable for more than 30 days and moves generally upstream, entering the Caribbean Sea. The sensitivities of the LC for SST generally remain closer to the surface and move at speeds consistent with advection by the high-speed core of

  18. Adjoint sensitivity studies of loop current and eddy shedding in the Gulf of Mexico

    KAUST Repository

    Gopalakrishnan, Ganesh

    2013-07-01

    Adjoint model sensitivity analyses were applied for the loop current (LC) and its eddy shedding in the Gulf of Mexico (GoM) using the MIT general circulation model (MITgcm). The circulation in the GoM is mainly driven by the energetic LC and subsequent LC eddy separation. In order to understand which ocean regions and features control the evolution of the LC, including anticyclonic warm-core eddy shedding in the GoM, forward and adjoint sensitivities with respect to previous model state and atmospheric forcing were computed using the MITgcm and its adjoint. Since the validity of the adjoint model sensitivities depends on the capability of the forward model to simulate the real LC system and the eddy shedding processes, a 5 year (2004–2008) forward model simulation was performed for the GoM using realistic atmospheric forcing, initial, and boundary conditions. This forward model simulation was compared to satellite measurements of sea-surface height (SSH) and sea-surface temperature (SST), and observed transport variability. Despite realistic mean state, standard deviations, and LC eddy shedding period, the simulated LC extension shows less variability and more regularity than the observations. However, the model is suitable for studying the LC system and can be utilized for examining the ocean influences leading to a simple, and hopefully generic LC eddy separation in the GoM. The adjoint sensitivities of the LC show influences from the Yucatan Channel (YC) flow and Loop Current Frontal Eddy (LCFE) on both LC extension and eddy separation, as suggested by earlier work. Some of the processes that control LC extension after eddy separation differ from those controlling eddy shedding, but include YC through-flow. The sensitivity remains stable for more than 30 days and moves generally upstream, entering the Caribbean Sea. The sensitivities of the LC for SST generally remain closer to the surface and move at speeds consistent with advection by the high-speed core of

  19. Detection and characterization of diverse coccidian protozoa shed by California sea lions

    Directory of Open Access Journals (Sweden)

    Yvette A. Girard

    2016-04-01

    Full Text Available Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris. California sea lions (Zalophus californianus, whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina. In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi diagnosed with protozoal disease in Oregon (USA. Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near

  20. On vortex shedding and prediction of vortex-induced vibrations of circular cylinders

    Energy Technology Data Exchange (ETDEWEB)

    Halse, Karl Henning

    1998-12-31

    In offshore installations, many crucial components can be classified as slender marine structures: risers, mooring lines, umbilicals and cables, pipelines. This thesis studies the vortex shedding phenomenon and the problem of predicting vortex-induced vibrations of such structures. As the development of hydrocarbons move to deeper waters, the importance of accurately predicting the vortex-induced response has increased and so the need for proper response prediction methods is large. This work presents an extensive review of existing research publications about vortex shedding from circular cylinders and the vortex-induced vibrations of cylinders and the different numerical approaches to modelling the fluid flow. The response predictions from different methods are found to disagree, both in response shapes and in vibration amplitudes. This work presents a prediction method that uses a fully three-dimensional structural finite element model integrated with a laminar two-dimensional Navier-Stokes solution modelling the fluid flow. This solution is used to study the flow both around a fixed cylinder and in a flexibly mounted one-degree-of-freedom system. It is found that the vortex-shedding process (in the low Reynolds number regime) is well described by the computer program, and that the vortex-induced vibration of the flexibly mounted section do reflect the typical dynamic characteristics of lock-in oscillations. However, the exact behaviour of the experimental results found in the literature was not reproduced. The response of the three-dimensional structural model is larger than the expected difference between a mode shape and a flexibly mounted section. This is due to the use of independent hydrodynamic sections along the cylinder. The predicted response is not unrealistic, and the method is considered a powerful tool. 221 refs., 138 figs., 36 tabs.

  1. Detection and characterization of diverse coccidian protozoa shed by California sea lions

    Science.gov (United States)

    Girard, Yvette A.; Johnson, Christine K.; Fritz, Heather M.; Shapiro, Karen; Packham, Andrea E.; Melli, Ann C.; Carlson-Bremer, Daphne; Gulland, Frances M.; Rejmanek, Daniel; Conrad, Patricia A.

    2015-01-01

    Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris). California sea lions (Zalophus californianus), whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina). In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi) diagnosed with protozoal disease in Oregon (USA). Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near-shore marine

  2. Detection and characterization of diverse coccidian protozoa shed by California sea lions.

    Science.gov (United States)

    Girard, Yvette A; Johnson, Christine K; Fritz, Heather M; Shapiro, Karen; Packham, Andrea E; Melli, Ann C; Carlson-Bremer, Daphne; Gulland, Frances M; Rejmanek, Daniel; Conrad, Patricia A

    2016-04-01

    Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris). California sea lions (Zalophus californianus), whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina). In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi) diagnosed with protozoal disease in Oregon (USA). Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near-shore marine

  3. On vortex shedding and prediction of vortex-induced vibrations of circular cylinders

    Energy Technology Data Exchange (ETDEWEB)

    Halse, Karl Henning

    1997-12-31

    In offshore installations, many crucial components can be classified as slender marine structures: risers, mooring lines, umbilicals and cables, pipelines. This thesis studies the vortex shedding phenomenon and the problem of predicting vortex-induced vibrations of such structures. As the development of hydrocarbons move to deeper waters, the importance of accurately predicting the vortex-induced response has increased and so the need for proper response prediction methods is large. This work presents an extensive review of existing research publications about vortex shedding from circular cylinders and the vortex-induced vibrations of cylinders and the different numerical approaches to modelling the fluid flow. The response predictions from different methods are found to disagree, both in response shapes and in vibration amplitudes. This work presents a prediction method that uses a fully three-dimensional structural finite element model integrated with a laminar two-dimensional Navier-Stokes solution modelling the fluid flow. This solution is used to study the flow both around a fixed cylinder and in a flexibly mounted one-degree-of-freedom system. It is found that the vortex-shedding process (in the low Reynolds number regime) is well described by the computer program, and that the vortex-induced vibration of the flexibly mounted section do reflect the typical dynamic characteristics of lock-in oscillations. However, the exact behaviour of the experimental results found in the literature was not reproduced. The response of the three-dimensional structural model is larger than the expected difference between a mode shape and a flexibly mounted section. This is due to the use of independent hydrodynamic sections along the cylinder. The predicted response is not unrealistic, and the method is considered a powerful tool. 221 refs., 138 figs., 36 tabs.

  4. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

    Science.gov (United States)

    Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

    2016-01-01

    Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

  5. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Directory of Open Access Journals (Sweden)

    Stacey X Xu

    Full Text Available HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  6. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Science.gov (United States)

    Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D

    2018-01-01

    HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  7. Microparticles shed from multidrug resistant breast cancer cells provide a parallel survival pathway through immune evasion.

    Science.gov (United States)

    Jaiswal, Ritu; Johnson, Michael S; Pokharel, Deep; Krishnan, S Rajeev; Bebawy, Mary

    2017-02-06

    Breast cancer is the most frequently diagnosed cancer in women. Resident macrophages at distant sites provide a highly responsive and immunologically dynamic innate immune response against foreign infiltrates. Despite extensive characterization of the role of macrophages and other immune cells in malignant tissues, there is very little known about the mechanisms which facilitate metastatic breast cancer spread to distant sites of immunological integrity. The mechanisms by which a key healthy defense mechanism fails to protect distant sites from infiltration by metastatic cells in cancer patients remain undefined. Breast tumors, typical of many tumor types, shed membrane vesicles called microparticles (MPs), ranging in size from 0.1-1 μm in diameter. MPs serve as vectors in the intercellular transfer of functional proteins and nucleic acids and in drug sequestration. In addition, MPs are also emerging to be important players in the evasion of cancer cell immune surveillance. A comparative analysis of effects of MPs isolated from human breast cancer cells and non-malignant human brain endothelial cells were examined on THP-1 derived macrophages in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine analysis, cell chemotaxis and phagocytosis, immunolabelling, flow cytometry and confocal imaging. Student's t-test or a one-way analysis of variance (ANOVA) was used for comparison and statistical analysis. In this paper we report on the discovery of a new cellular basis for immune evasion, which is mediated by breast cancer derived MPs. MPs shed from multidrug resistant (MDR) cells were shown to selectively polarize macrophage cells to a functionally incapacitated state and facilitate their engulfment by foreign cells. We propose this mechanism may serve to physically disrupt the inherent immune response prior to cancer cell colonization whilst releasing mediators required for the recruitment of distant immune cells. These findings

  8. 40 CFR 63.305 - Alternative standards for coke oven doors equipped with sheds.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Alternative standards for coke oven doors equipped with sheds. 63.305 Section 63.305 Protection of Environment ENVIRONMENTAL PROTECTION... SOURCE CATEGORIES National Emission Standards for Coke Oven Batteries § 63.305 Alternative standards for...

  9. An investigation of the shedding of macromolecules from the Ehrlich mouse ascites tumor cell

    International Nuclear Information System (INIS)

    Edwards, E.H.

    1984-01-01

    The spontaneous release, or shedding, of cell surface components into the extracellular medium may be important in the determination of several features of the cancer cell phenotype. The release of macromolecules from the Erhlich mouse ascites tumor cell was studied under a variety of experimental conditions to elucidate the origin and the underlying mechanisms of release. The extrinsic macromolecules are a diverse group with apparent molecular weights ranging from 13,500 to 400,000 daltons. External labeling of the cell surface with tritiated 4,4'-diisothiocyano-1,2-diphenylethane-2,2-disulfonic acid ([ 3 H]H 2 DIDS) reveals a slow loss of labeled components at 4 degrees C, while at 21 degrees C and 37 degrees C an initial rapid loss is followed by a slower release. In vitro metabolic labeling with [1- 14 C]-D-glucosamine hydrochloride, D-[2- 3 H]-mannose and various [ 3 H]-L-amino acids results in the appearance of labeled macromolecules in the medium suggesting tumor, not mouse, origin. These data suggest that the extrinsic macromolecules originate from the cell surface. Macromolecules are shed by a temperature and pH sensitive process. These results suggest that a limited proteolytic digestion, or sublethal autolysis, of the cell surface may occur in this system. The macromolecules shed by the Ehrlich cell originate from the surface and are probably released by sublethal autolysis, direct secretion and a passive process

  10. EVIDENCE OF PSEUDORABIES VIRUS SHEDDING IN FERAL SWINE ( SUS SCROFA) POPULATIONS OF FLORIDA, USA.

    Science.gov (United States)

    Hernández, Felipe A; Sayler, Katherine A; Bounds, Courtney; Milleson, Michael P; Carr, Amanda N; Wisely, Samantha M

    2018-01-01

    :  Feral swine ( Sus scrofa) are a pathogen reservoir for pseudorabies virus (PrV). The virus can be fatal to wildlife and contributes to economic losses in the swine industry worldwide. National surveillance efforts in the US use serology to detect PrV-specific antibodies in feral swine populations, but PrV exposure is not a direct indicator of pathogen transmission among conspecifics or to non-suid wildlife species. We measured antibody production and the presence of PrV DNA in four tissue types from feral swine populations of Florida, US. We sampled blood, nasal, oral, and genital swabs from 551 individuals at 39 sites during 2014-16. Of the animals tested for antibody production, 224 of 436 (51%) feral swine were antibody positive while 38 of 549 feral swine (7%) tested for viral shedding were quantitative polymerase chain reaction (qPCR)-positive for PrV. The detection of PrV DNA across all the collected sample types (blood, nasal, oral, and genital [vaginal] swabs) suggested viral shedding via direct (oronasal or venereal), and potentially indirect (through carcass consumption), routes of transmission among infected and susceptible animals. Fourteen of 212 seronegative feral swine were qPCR-positive, indicating 7% false negatives in the serologic assay. Our findings suggest that serology may underestimate the actual infection risk posed by feral swine to other species and that feral swine populations in Florida are capable of shedding the virus through multiple routes.

  11. Impact of Shed/Soluble targets on the PK/PD of approved therapeutic monoclonal antibodies.

    Science.gov (United States)

    Samineni, Divya; Girish, Sandhya; Li, Chunze

    2016-12-01

    Suboptimal treatment for monoclonal antibodies (mAbs) directed against endogenous circulating soluble targets and the shed extracellular domains (ECD) of the membrane-bound targets is an important clinical concern due to the potential impact of mAbs on the in vivo efficacy and safety. Consequently, there are considerable challenges in the determination of an optimal dose and/or dosing regimen. Areas covered: This review outlines the impact of shed antigen targets from membrane-bound proteins and soluble targets on the PK and/or PD of therapeutic mAbs that have been approved in the last decade. We discuss various bioanalytical techniques that have facilitated the interpretation of the PK/PD properties of therapeutic mAbs and also considered the factors that may impact such measurements. Quantitative approaches include target-mediated PK models and bi- or tri-molecular interaction PK/PD models that describe the relationships between the antibody PK and the ensuing effects on PD biomarkers, to facilitate the mAb PK/PD characterization. Expert commentary: The proper interpretation of PK/PD relationships through the integrated PK/PD modeling and bioanalytical strategy facilitates a mechanistic understanding of the disease processes and dosing regimen optimization, thereby offering insights into developing effective therapeutic regimens. This review provides an overview of the impact of soluble targets or shed ECD on mAb PK/PD properties. We provide examples of quantitative approaches that facilitate the characterization of mAb PK/PD characteristics and their corresponding bioanalytical strategies.

  12. Epstein-Barr virus shedding by astronauts during space flight

    Science.gov (United States)

    Pierson, D. L.; Stowe, R. P.; Phillips, T. M.; Lugg, D. J.; Mehta, S. K.

    2005-01-01

    Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected from astronauts before, during, and after 10 space shuttle missions of 5-14 days duration. At one time point or another, EBV was detected in saliva from each of the astronauts. Of 1398 saliva specimens from 32 astronauts, polymerase chain reaction analysis showed that 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies from samples taken during the flights was 417 per mL, significantly greater (p<.05) than the number of viral copies from the preflight (40) and postflight (44) phases. In contrast, the control subjects shed EBV DNA with a frequency of 3.7% and mean number of EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (p<.05) greater than baseline levels. On landing day, urinary levels of cortisol and catecholamines were greater than their preflight values. In a limited study (n=5), plasma levels of substance P and other neuropeptides were also greater on landing day. Increases in the number of viral copies and in the amount of EBV-specific antibody were consistent with EBV reactivation before, during, and after space flight.

  13. HIV shedding in cervico-vaginal secretions in pregnant women.

    Science.gov (United States)

    Gardella, Barbara; Roccio, Marianna; Maccabruni, Anna; Mariani, Bianca; Panzeri, Lucia; Zara, Francesca; Spinillo, Arsenio

    2011-07-01

    The purpose of this study was to evaluate the presence of HIV-1 in cervico-vaginal secretions of pregnant as compared to non-pregnant HIV-seropositive women. We compared 43 known HIV seropositive pregnant patients versus 241 age-matched (± 2 years) control non-pregnant HIV-seropositive subjects. In pregnant patients blood and cervico-vaginal samples were obtained during each trimester of pregnancy. In control subjects the same samples were obtained at enrolment. HIV-1 RNA was measured in plasma; proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA in cervico-vaginal secretion by competitive polymerase chain reaction (cRT-PCR) and reverse transcriptase PCR. The genital shedding of HIV-DNA (22/43 as compared to 79/241, p = 0.02), and cell-free HIV-RNA detection (26/43 as compared to 72/241, p pregnant than in non pregnant women. Pregnancy correlated with a significant positive trend in the cervico-vaginal load of HIV-DNA (Spearman Rho= 0.149, p= 0.012), and cell-free HIV-RNA (Spearman Rho= 0.253, p HIV-RNA transcripts (Spearman Rho = 0.06, p= 0.31). After correction for potential confounders, first trimester pregnant women had increased rates of genital HIV- DNA (odds ratio = 1.94, 95% confidence interval = 1.01 3.78) and cell-free HIV-RNA (odds ratio = 4.07, 95% confidence interval = 1.97 8.41) detection compared to nonpregnant controls. The shedding of genital HIV was increased in pregnant compared to non pregnant subjects, even in patients with undetectable viremia. In this low-risk HIV-positive population the risks of vertical or horizontal transmissions should not be underestimated.

  14. Lagrangian Visualization and Real-Time Identification of the Vortex Shedding Time in the Wake of a Circular Cylinder

    Science.gov (United States)

    Rockwood, Matthew P.

    The flow around a circular cylinder, a canonical bluff body, has been extensively studied in the literature to determine the mechanisms that cause the formation of vortices in the cylinder wake. Understanding of these mechanisms has led to myriad attempts to control the vortices either to mitigate the oscillating forces they cause, or to augment them in order to enhance mixing in the near-wake. While these flow control techniques have been effective at low Reynolds numbers, they generally lose effectiveness or require excessive power at Reynolds numbers commonly experienced in practical applications. For this reason, new methods for identifying the locations of vortices and their shedding time could increase the effectiveness of the control techniques. In the current work, two-dimensional, two-component velocity data was collected in the wake of a circular cylinder using a planar digital particle image velocimetry (DPIV) measurement system at Reynolds numbers of 9,000 and 19,000. This experimental data, as well as two-dimensional simulation data at a Reynolds number of 150, and three-dimensional simulation data at a Reynolds number of 400, is used to calculate the finite-time Lyapunov exponent (FTLE) field. The locations of Lagrangian saddles, identified as non-parallel intersections of positive and negative time FTLE ridges, are shown to indicate the timing of von Karman vortex shedding in the wake of a circular cylinder. The Lagrangian saddle found upstream of a forming and subsequently shedding vortex is shown to clearly accelerate away from the cylinder surface as the vortex begins to shed. This provides a novel, objective method to determine the timing of vortex shedding. The saddles are impossible to track in real-time, however, since future flow field data is needed for the computation of the FTLE fields. In order to detect the Lagrangian saddle acceleration without direct access to the FTLE, the saddle dynamics are connected to measurable surface quantities

  15. Deposit Shedding in Biomass-fired Boilers: Shear Adhesion Strength Measurements

    DEFF Research Database (Denmark)

    Laxminarayan, Yashasvi; Jensen, Peter Arendt; Wu, Hao

    2016-01-01

    . Therefore, timely removal of ash deposits is essential for optimal boiler operation. In order to improve the understanding of deposit shedding in boilers, this study investigates the shear adhesion strength of biomass ash deposits on superheater tubes. Artificial biomass ash deposits were prepared...... on superheater tubes and sintered in an oven at temperatures up to 1000 °C. Subsequently, the deposits were sheared off by an electrically controlled arm, and the corresponding adhesion strength was measured. The results reveal the effect of temperature, deposit composition, sintering duration, and steel type...... on the adhesion strength....

  16. Viral shedding and emission of airborne infectious bursal disease virus from a broiler room

    NARCIS (Netherlands)

    Zhao, Y.; Aarnink, A.J.A.; Cambra-Lopez, M.; Fabri, T.

    2013-01-01

    1. The significance of airborne transmission in epidemics of infectious diseases in the livestock production industry remains unclear. The study therefore investigated the shedding route (faeces vs. exhaled air) of a vaccine strain of infectious bursal disease virus (IBDV) by broilers and the

  17. PV working with industry, Second Quarter, 1999: Shedding light on the matter

    International Nuclear Information System (INIS)

    Moon, S.; Poole, L.

    1999-01-01

    NREL PV Working With Industry is a quarterly newsletter devoted to the research, development, and deployment performed by NREL staff in concert with their industry and university partners. The Second Quarter, 1999 issue, titled ''Shedding Light on the Matter,'' focuses on the PV-related research activities of NREL's Basic Sciences Center. The editorialist is Satyen Deb, in his role as Director of the Basic Sciences Center

  18. Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

    International Nuclear Information System (INIS)

    Hore, Paromita; Zartarian, Valerie; Xue Jianping; Ozkaynak, Haluk; Wang, S.-W.; Yang, Y.-C.; Chu, P.-Ling; Sheldon, Linda; Robson, Mark; Needham, Larry; Barr, Dana; Freeman, Natalie; Georgopoulos, Panos; Lioy, Paul J.

    2006-01-01

    The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found in the

  19. Falling, flapping, flying, swimming,...: High-Re fluid-solid interactions with vortex shedding

    Science.gov (United States)

    Michelin, Sebastien Honore Roland

    The coupling between the motion of a solid body and the dynamics of the surrounding flow is essential to the understanding of a large number of engineering and physical problems, from the stability of a slender structure exposed to the wind to the locomotion of insects, birds and fishes. Because of the strong coupling on a moving boundary of the equations for the solid and fluid, the simulation of such problems is computationally challenging and expensive. This justifies the development of simplified models for the fluid-solid interactions to study their physical properties and behavior. This dissertation proposes a reduced-order model for the interaction of a sharp-edged solid body with a strongly unsteady high Reynolds number flow. In such a case, viscous forces in the fluid are often negligible compared to the fluid inertia or the pressure forces, and the thin boundary layers separate from the solid at the edges, leading to the shedding of large and persistent vortices in the solid's wake. A general two-dimensional framework is presented based on complex potential flow theory. The formation of the solid's vortical wake is accounted for by the shedding of point vortices with unsteady intensity from the solid's sharp edges, and the fluid-solid problem is reformulated exclusively as a solid-vortex interaction problem. In the case of a rigid solid body, the coupled problem is shown to reduce to a set of non-linear ordinary differential equations. This model is used to study the effect of vortex shedding on the stability of falling objects. The solid-vortex model is then generalized to study the fluttering instability and non-linear flapping dynamics of flexible plates or flags. The uttering instability and resulting flapping motion result from the competing effects of the fluid forcing and of the solid's flexural rigidity and inertia. Finally, the solid-vortex model is applied to the study of the fundamental effect of bending rigidity on the flapping performance of

  20. Cell kinetics of the marine sponge Halisarca caerulea reveal rapid cell turnover and shedding

    NARCIS (Netherlands)

    Goeij, de J.M.; Kluijver, de A.; Duyl, van F.C.; Vacelet, J.; Wijffels, R.H.; Goeij, de A.F.P.M.; Cleutjens, J.P.M.; Schutte, B.

    2009-01-01

    This study reveals the peculiar in vivo cell kinetics and cell turnover of the marine sponge Halisarca caerulea under steady-state conditions. The tropical coral reef sponge shows an extremely high proliferation activity, a short cell cycle duration and massive cell shedding. Cell turnover is

  1. NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

    Science.gov (United States)

    Tang, Li-li; Wu, Yuan-bo; Fang, Chuan-qin; Qu, Ping; Gao, Zong-liang

    2016-01-15

    Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Factors associated with fecal-shedding of Salmonella spp by horses on US operations

    Directory of Open Access Journals (Sweden)

    Losinger W.C.

    2002-01-01

    Full Text Available In a cross-sectional national study that included 972 operations with > 3 horses on 1/1/98 in 28 states in the USA, 8,417 fecal specimens were collected from horses and cultured to test for the presence of Salmonella spp. Operations were characterized as Salmonella spp-positive if at least one fecal specimen tested positive for Salmonella spp. Percentages of Salmonella spp-positive operations were computed by management and other factors (collected from operation-level questionnaires that were hypothesized to be related to fecal shedding of Salmonella spp. A logistic-regression model was constructed to identify factors associated with horses? shedding Salmonella spp in feces on an operation. The odds of an operation being Salmonella spp positive increased as the number of resident horses increased. In addition, the following factors were found to be associated with increased odds of an operation being Salmonella spp positive: horses were used primarily for breeding; operation cleanliness was characterized as poor by the data collector; and new resident equids had been added to the operation without routine quarantine.

  3. Shedding of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus from adult and pediatric bathers in marine waters

    Directory of Open Access Journals (Sweden)

    Sinigalliano Christopher D

    2011-01-01

    Full Text Available Abstract Background Staphylococcus aureus including methicillin resistant S. aureus, MRSA, are human colonizing bacteria that commonly cause opportunistic infections primarily involving the skin in otherwise healthy individuals. These infections have been linked to close contact and sharing of common facilities such as locker rooms, schools and prisons Waterborne exposure and transmission routes have not been traditionally associated with S. aureus infections. Coastal marine waters and beaches used for recreation are potential locations for the combination of high numbers of people with close contact and therefore could contribute to the exposure to and infection by these organisms. The primary aim of this study was to evaluate the amount and characteristics of the shedding of methicillin sensitive S. aureus, MSSA and MRSA by human bathers in marine waters. Results Nasal cultures were collected from bathers, and water samples were collected from two sets of pools designed to isolate and quantify MSSA and MRSA shed by adults and toddlers during exposure to marine water. A combination of selective growth media and biochemical and polymerase chain reaction analysis was used to identify and perform limited characterization of the S. aureus isolated from the water and the participants. Twelve of 15 MRSA isolates collected from the water had identical genetic characteristics as the organisms isolated from the participants exposed to that water while the remaining 3 MRSA were without matching nasal isolates from participants. The amount of S. aureus shed per person corresponded to 105 to 106 CFU per person per 15-minute bathing period, with 15 to 20% of this quantity testing positive for MRSA. Conclusions This is the first report of a comparison of human colonizing organisms with bacteria from human exposed marine water attempting to confirm that participants shed their own colonizing MSSA and MRSA into their bathing milieu. These findings clearly

  4. Experimental Investigation of Vortex Shedding in Flow Over Second-Generation, Controlled-Diffusion, Compressor Blades in Cascade

    National Research Council Canada - National Science Library

    Brown, Peter

    2002-01-01

    An investigation of vortex shedding downstream of a cascade of second-generation, controlled-diffusion, compressor stator blades, at off-design inlet-flow angles of 31, 33 and 35 degrees and Reynolds...

  5. Detection of feline coronavirus in cheetah (Acinonyx jubatus) feces by reverse transcription-nested polymerase chain reaction in cheetahs with variable frequency of viral shedding.

    Science.gov (United States)

    Gaffney, Patricia M; Kennedy, Melissa; Terio, Karen; Gardner, Ian; Lothamer, Chad; Coleman, Kathleen; Munson, Linda

    2012-12-01

    Cheetahs (Acinonyx jubatus) are a highly threatened species because of habitat loss, human conflict, and high prevalence of disease in captivity. An epidemic of feline infectious peritonitis and concern for spread of infectious disease resulted in decreased movement of cheetahs between U.S. zoological facilities for managed captive breeding. Identifying the true feline coronavirus (FCoV) infection status of cheetahs is challenging because of inconsistent correlation between seropositivity and fecal viral shedding. Because the pattern of fecal shedding of FCoV is unknown in cheetahs, this study aimed to assess the frequency of detectable fecal viral shedding in a 30-day period and to determine the most efficient fecal sampling strategy to identify cheetahs shedding FCoV. Fecal samples were collected from 16 cheetahs housed at seven zoological facilities for 30 to 46 consecutive days; the samples were evaluated for the presence of FCoV by reverse transcription-nested polymerase chain reaction (RT-nPCR). Forty-four percent (7/16) of cheetahs had detectable FCoV in feces, and the proportion of positive samples for individual animals ranged from 13 to 93%. Cheetahs shed virus persistently, intermittently, or rarely over 30-46 days. Fecal RT-nPCR results were used to calculate the probability of correctly identifying a cheetah known to shed virus given multiple hypothetical fecal collection schedules. The most efficient hypothetical fecal sample collection schedule was evaluation of five individual consecutive fecal samples, resulting in a 90% probability of identifying a known shedder. Demographic and management risk factors were not significantly associated (P cheetahs shed virus intermittently to rarely, fecal sampling schedules meant to identify all known shedders would be impractical with current tests and eradication of virus from the population unreasonable. Managing the captive population as endemically infected with FCoV may be a more feasible approach.

  6. EPA's SHEDS-multimedia model: children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data

    Science.gov (United States)

    The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cum...

  7. Characterizing cycle-to-cycle variations of the shedding cycle in the turbulent wake of a normal flat plate using generalized phase averages

    Science.gov (United States)

    Martinuzzi, Robert

    2016-11-01

    Quasi-periodic vortex shedding in the turbulent wake of a thin-flat plate placed normal to a uniform stream at Reynolds number of 6700 is investigated based on Particle Image Velocimetry experiments. The wake structure and vortex formation are characterized using a generalized phase average (GPA), a refinement of the triple decomposition of Reynolds and Hussain (1970) incorporating elements of mean-field theory (Stuart, 1958). The resulting analysis highlights the importance of cycle-to-cycle variations in characterizing vortex formation, wake topology and the residual turbulent Reynolds Stresses. For example, it is shown that during high-amplitude cycles vorticity is strongly concentrated within the well-organized shed vortices, whereas during low-amplitude cycles the shed vortices are highly distorted resulting in significant modulation of the shedding frequency. It is found that high-amplitude cycles contribute more to the coherent Reynolds stress field while the low-amplitude cycles contribute to the residual stress field. It is further shown that traditional phase-averaging techniques lead to an over-estimation of the residual stress field. Natural Sciences and Engineering Research Council of Canada.

  8. Discovery of a new strain of murine rotavirus that is consistently shed in large quantities after oral inoculation of adult mice

    International Nuclear Information System (INIS)

    McNeal, Monica M.; Belli, Janine; Basu, Mitali; Choi, Anthony H.-C.; Ward, Richard L.

    2004-01-01

    In 1990, we developed the adult mouse model for studies on active immunity against shedding of the EDIM strain of murine rotavirus. Low and inconsistent levels of EDIM shedding in some strains of adult mice, particularly those on C57BL/6 backgrounds, established the need for an alternative murine rotavirus strain for these studies. Fortuitously, such a rotavirus strain was obtained from mice housed within the conventional colony at Children's Hospital. This strain, named EMcN, was clearly distinguishable from EDIM based on electropherotype. Furthermore, sequence analyses of VP4 and VP7 genes of EMcN revealed non-identities in 5% of the amino acids of both proteins relative to EDIM but established EMcN as another G3P[16] strain of murine rotavirus. Subgroup analysis showed EMcN belonged to SG1 while EDIM was found to be non-SG1/SG2. Similarly, unlike EDIM, the EMcN strain was identified as serotype G3 based on neutralization by hyperimmune antisera developed against prototype human and simian G3 rotavirus strains. Although EDIM produced more days of diarrhea and was shed in greater quantities in neonatal BALB/c mice, EMcN was shed in much greater quantities in adult BALB/c mice. More importantly, in contrast to the EDIM strain, EMcN was shown to be consistently shed in large quantities in adult C57BL/6 mice and ko mice on this background. Therefore, it is recommended that the EMcN strain be used for future challenge studies with mice on this background

  9. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes

    Science.gov (United States)

    Oliveira, Ryan D.; Mousel, Michelle R.; Pabilonia, Kristy L.; Highland, Margaret A.; Taylor, J. Bret; Knowles, Donald P.

    2017-01-01

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007–2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such

  10. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Directory of Open Access Journals (Sweden)

    Ryan D Oliveira

    Full Text Available Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05. Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%. While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted

  11. Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

    Science.gov (United States)

    Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

    2013-01-01

    To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, pgenital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

  12. Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment

    Science.gov (United States)

    Peron, Rafaela; Vatanabe, Izabela Pereira; Manzine, Patricia Regina; Camins, Antoni

    2018-01-01

    ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review. PMID:29382156

  13. PV working with industry, Second Quarter, 1999: Shedding light on the matter

    Energy Technology Data Exchange (ETDEWEB)

    Moon, S.; Poole, L.

    1999-09-13

    NREL PV Working With Industry is a quarterly newsletter devoted to the research, development, and deployment performed by NREL staff in concert with their industry and university partners. The Second Quarter, 1999 issue, titled ''Shedding Light on the Matter,'' focuses on the PV-related research activities of NREL's Basic Sciences Center. The editorialist is Satyen Deb, in his role as Director of the Basic Sciences Center.

  14. Role of Protein Kinase C in Endothelin Converting Enzyme-1 trafficking and shedding from endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@med.monash.edu.au [Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3800 (Australia); Tochon-Danguy, Natalie; Ian Smith, A. [Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3800 (Australia)

    2010-07-23

    Research highlights: {yields} PKC activation increases the trafficking of ECE-1 to the cell surface. {yields} This in turn leads to an increase in the amount of ECE-1 shed. {yields} Only the catalytically active C-terminal region is shed from the cell surface. -- Abstract: This study aimed to determine the consequences of Protein Kinase C (PKC) mediated Endothelin Converting Enzyme-1 (ECE-1) phosphorylation and its relationship to ECE-1 expression and shedding. The proteins on the surface of EA.hy926 cells were labelled with EZ-Link NHS-SS-Biotin both prior to (control) and following stimulation by 2 {mu}M phorbol 12-myristate 13-acetate (PMA) which activates PKC. The biotinylated proteins were isolated using neutravidin beads, resolved by gel electrophoresis and analysed by western blotting using anti-ECE-1 antibodies. Significant increase in ECE-1 expression at the cell surface was observed following stimulation by PMA, compared to unstimulated control cells (170 {+-} 32.3% of control, n = 5). The ECE-1 activity (expressed as {mu}M substrate cleaved/min) was determined by monitoring the cleavage of a quenched fluorescent substrate. The specificity of cleavage was confirmed using the ECE-1 inhibitor (CGS35066). The stimulation of cells by PMA (1 {mu}M, 6 h) significantly increased the ECE-1 activity (0.28 {+-} 0.02; n = 3) compared to the control (0.07 {+-} 0.02; n = 3). This increase was prevented by prior incubation with the PKC inhibitor bisindolymaleimide (BIM; 2 {mu}M for 1 h; 0.10 {+-} 0.01; n = 3). Treatment with PMA also increased the activity of ECE-1 in the media (0.18 {+-} 0.01; n = 3) compared to control (0.08 {+-} 0.01; n = 3). In addition, this study confirmed by western immunoblotting that only the extracellular region of ECE-1 is released from the cell surface. These data indicate for the first time that PKC activation induces the trafficking and shedding of ECE to and from the cell surface, respectively.

  15. Shedding and seroprevalence of pathogenic Leptospira spp. in sheep and cattle at a New Zealand Abattoir.

    Science.gov (United States)

    Fang, F; Collins-Emerson, J M; Cullum, A; Heuer, C; Wilson, P R; Benschop, J

    2015-06-01

    A cross-sectional study was carried out on sheep and cattle slaughtered at a New Zealand abattoir from September to November 2010 to investigate the supplier-specific shedding rate, renal carriage rate and seroprevalence of leptospires. In the 2008/2009 season, this abattoir experienced three human leptospirosis cases from 20 staff, of which two were hospitalized. Urine, kidney and blood samples were collected from carcasses of 399 sheep (six suppliers, 17 slaughter lines) and 146 cattle (three suppliers, 22 slaughter lines). The urine and kidney samples were tested by quantitative real-time PCR (qPCR), while serum samples (from coagulated blood samples) were tested by microscopic agglutination test (MAT). In total, 27% (73/274; 95% CI: 18-37) of urine samples tested positive by qPCR. Species-specific shedding rates (prevalence of positive urine qPCR) were 31% (95% CI: 17-48) for sheep and 21% (95% CI: 14-30) for cattle. For 545 kidney samples tested, 145 were qPCR positive (27%; 95% CI: 17-39). The average prevalence of kidney qPCR positivity was 29% (95% CI: 17-45) for sheep and 21% (95% CI: 15-28) for cattle. Three hundred and thirty of 542 sampled sheep and cattle had antibodies against Leptospira borgpetersenii serovar Hardjobovis (Hardjobovis) and/or Leptospira interrogans serovar Pomona (Pomona), based on reciprocal MAT titre ≥1 : 48 (overall seroprevalence of 61%; 95% CI: 48-73). Seroprevalence was 57% (95% CI: 40-72) for sheep and 73% (95% CI: 59-83) for cattle. Among the seropositive animals, 41% (70/170; 95% CI: 30-54) were shedding (tested positive by urine qPCR) and 42% (137/330; 95% CI: 30-54) had renal carriage (tested positive by kidney qPCR). Some risk management options for abattoirs or farms to prevent human leptospirosis infections include vaccination of maintenance hosts, the use of personal protective equipment, and the application of urine qPCR to detect shedding status of stock as surveillance and as an alert. © 2014 Blackwell Verlag

  16. Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa.

    Directory of Open Access Journals (Sweden)

    Joshua T Schiffer

    Full Text Available A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2 in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/μL. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. Peak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

  17. Identification of two novel coccidian species shed by California sea lions (Zalophus californianus).

    Science.gov (United States)

    Carlson-Bremer, Daphne; Johnson, Christine K; Miller, Robin H; Gulland, Frances M D; Conrad, Patricia A; Wasmuth, James D; Colegrove, Kathleen M; Grigg, Michael E

    2012-04-01

    Routine fecal examination revealed novel coccidian oocysts in asymptomatic California sea lions (Zalophus californianus) in a rehabilitation facility. Coccidian oocysts were observed in fecal samples collected from 15 of 410 California sea lions admitted to The Marine Mammal Center between April 2007 and October 2009. Phylogenetic analysis using the full ITS-1 region, partial small subunit 18S rDNA sequence, and the Apicomplexa rpoB region identified 2 distinct sequence clades, referred to as Coccidia A and Coccidia B, and placed them in the Sarcocystidae, grouped with the tissue-cyst-forming coccidia. Both sequence clades resolved as individual taxa at ITS-1 and rpoB and were most closely related to Neospora caninum. Coccidia A was identified in 11 and Coccidia B in 4 of 12 sea lion oocyst samples successfully sequenced (3 of those sea lions were co-infected with both parasites). Shedding of Coccidia A oocysts was not associated with age class, sex, or stranding location, but yearlings represented the majority of shedders (8/15). This is the first study to use molecular phylogenetics to identify and describe coccidian parasites shed by a marine mammal.

  18. Comparison of Diversities of Escherichia coli O157 Shed from a Cohort of Spring-Born Beef Calves at Pasture and in Housing

    Science.gov (United States)

    Vali, Leila; Pearce, Michael C.; Wisely, Karen A.; Hamouda, Ahmed; Knight, Hazel I.; Smith, Alastair W.; Amyes, Sebastian G. B.

    2005-01-01

    A cohort of spring-born beef calves demonstrated limited genetic and phenotypic diversity of Escherichia coli O157 when kept in a state of isolation. Despite this, there was a difference in the pulsed-field gel electrophoresis and phage types of isolates shed by cattle at pasture compared with those shed by the same cattle when weaned and housed. PMID:15746371

  19. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects.

    Science.gov (United States)

    Branco, Luis M; Grove, Jessica N; Moses, Lina M; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Schoepp, Randal J; Bausch, Daniel G; Garry, Robert F

    2010-11-09

    Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene [1, 2]. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV), a filovirus that also causes hemorrhagic fever with nearly 90 percent fatality rates [3 - 5]. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW), in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. It is reasonable to expect that a narrow window exists for detection of sGP1 as the sole

  20. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

    Directory of Open Access Journals (Sweden)

    Slack Barbara E

    2011-05-01

    Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

  1. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

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

    Science.gov (United States)

    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.; hide

    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 (Por=40 years old (P.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

  3. Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE

    Directory of Open Access Journals (Sweden)

    Miguel Cavadas

    2017-10-01

    Full Text Available Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme, is responsible for cleavage (“shedding” of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents. Here, we report a role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal that iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.

  4. Nocturnal drainage wind characteristics in two converging air sheds

    International Nuclear Information System (INIS)

    Gedayloo, T.; Clements, W.E.; Barr, S.; Archuleta, J.A.

    1980-01-01

    During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 25 0 C during summer and about 20 0 C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s -1 and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin

  5. HCMV gB shares structural and functional properties with gB proteins from other herpesviruses

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Sapna [Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111 (United States); Wisner, Todd W.; Johnson, David C. [Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239 (United States); Heldwein, Ekaterina E., E-mail: katya.heldwein@tufts.edu [Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111 (United States)

    2013-01-20

    Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.

  6. Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.

    Science.gov (United States)

    Yuan, Ping; Leser, George P; Demeler, Borries; Lamb, Robert A; Jardetzky, Theodore S

    2008-09-01

    The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

  7. Risk assessment modelling of fecal shedding caused by extended-spectrum cephalosporin-resistant Escherichia coli transmitted through waste milk fed to dairy pre-weaned calves.

    Science.gov (United States)

    Awosile, Babafela B; Smith, Ben A

    2017-12-01

    Waste milk feeding is a common practice in dairy operations. Regardless of the benefits of this practice to the dairy farmers, concerns from the potential dissemination of antimicrobial-resistant bacteria through the gut and subsequent shedding by calves into the environment are increasing. In this study, we employed Monte Carlo simulation to assess the risk of shedding extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R E. coli) caused by waste milk feeding in pre-weaned calves using an exponential dose-response model fit to data for E. coli O157:H7 in cattle. Data from pertinent studies were included in our model to predict the risk of shedding. The median (5th and 95th percentiles) for the daily risk of shedding ESC-R E. coli by calves fed only contaminated waste milk was predicted to be 2.9 × 10 -3 (2.1 × 10 -3 , 3.7 × 10 -3 ), representing a median daily risk of 29 out of 10,000 calves shedding ESC-R E. coli due to exclusive feeding of waste milk containing ESC-R E. coli. This median value was reduced by 94% when accounting for the proportion of waste milk that does not contain ESC-R E. coli. The overall risk of shedding ESC-R E. coli through the pre-weaning period for farms that feed waste milk to calves was 5.7 × 10 -3 (2.4 × 10 -3 , 1.1 × 10 -2 ), representing 57 out of 10,000 calves. When accounting for the proportion of farms that do not feed waste milk, the pre-weaning period risk was reduced by 23%. By varying the prevalence of ESC-R E. coli in waste milk using values of 3, 1.5, and 1%, the daily risk of shedding decreased by factors of 50, 65, and 82%, respectively, which supports the reduction of contamination or discontinuation of feeding waste milk containing ESC-R E. coli as major mitigation measures to reduce the risk of shedding caused by ingestion of resistant bacteria. It is anticipated that the effects of antimicrobial residues in waste milk, which was not considered herein due to lack of data, would further increase risks

  8. Predictors and risk factors for the intestinal shedding of Escherichia coli O157 among working donkeys (Equus asinus) in Nigeria

    Science.gov (United States)

    Jedial, Jesse T.; Shittu, Aminu; Tambuwal, Faruk M.; Abubakar, Mikail B.; Garba, Muhammed K.; Kwaga, Jacob P.; Fasina, Folorunso O.

    2015-01-01

    Objectives Escherichia coli are an important group of bacteria in the normal gastrointestinal system but can sometimes cause infections in domestic animals and man. Donkeys are routinely used as multipurpose animal but details of burdens of potentially infectious bacteria associated with it are limited. The prevalence and associations between intestinal shedding of E. coli O157 and animal characteristics and management factors were studied among 240 randomly selected working donkeys in north-western Nigeria. Design Four local government areas, of Sokoto State in north-western Nigeria were recruited in this study. A multistage randomised cluster design was used to select subjects and donkey owners within selected zones. Confirmation of infection was based on bacterial culture, isolation and biochemical test for E. coli O157 from faecal samples. Results Of the total bacteria isolated, 203 of the 329 (61.70 per cent) were E. coli, 76 of which was E. coli serotype O157. A multivariable logistic regression model was used to examine the relation between intestinal shedding of E. coli O157 and selected variables. The analysis yielded five potential predictors of shedding: soft faeces in donkeys, Akaza and Fari ecotypes of donkey were positive predictors while maize straw as feed and sampling during the cold dry period were negative predictors. Conclusions This study concludes that controlling intestinal shedding of E. coli O157 among working donkeys in Nigeria is possible using the identified predictors in planning appropriate interventions to reduced human risk of infection. PMID:26392892

  9. Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

    Energy Technology Data Exchange (ETDEWEB)

    Hore, Paromita [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[New York City Department of Health, 253 Broadway New York, New York 10007 (United States); Zartarian, Valerie; Xue Jianping; Ozkaynak, Haluk [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Wang, S.-W.; Yang, Y.-C.; Chu, P.-Ling; Robson, Mark; Georgopoulos, Panos [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States); Sheldon, Linda [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Needham, Larry Barr, Dana [Contemporary Pesticide Laboratory, Centers for Disease Control, 4770 Buford Highway, Atlanta, GA 30341 (United States); Freeman, Natalie [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[University of Florida, Gainesville, FL 32611 (United States); Lioy, Paul J. [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]. E-mail: plioy@eohsi.rutgers.edu

    2006-08-01

    The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found

  10. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality

    DEFF Research Database (Denmark)

    Boskovski, Marko T; Yuan, Shiaulou; Pedersen, Nis Borbye

    2013-01-01

    to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either...... by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio...... of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking...

  11. Consequence of temperature changes on cercarial shedding from Galba truncatula infected with Fasciola hepatica or Paramphistomum daubneyi

    Directory of Open Access Journals (Sweden)

    Rondelaud Daniel

    2013-01-01

    Full Text Available Experimental infections of Galba truncatula (two populations with Fasciola hepatica or Paramphistomum daubneyi were carried out to study the effect of water temperature changes (3 h at a mean of 12 °C every week on cercarial shedding during the patent period. The results were compared with those of control snails infected according to the same protocol and always maintained at 20 °C. Compared to controls, a significant increase in the number of cercariae-shedding snails, a significantly longer patent period and significantly greater cercarial production were noted in temperature-challenged snails, regardless of the type of digenean infection. In contrast, the number of incompletely formed metacercariae was significantly higher in temperature-challenged snails than in controls. Incompletely formed metacercariae of F. hepatica consisted of cysts whose colour remained whitish after shedding (25.4% for temperature-challenged snails or whose dome was flattened after encystment (74.6%. Those of P. daubneyi were totally dark brown or blackish after formation. These incomplete metacercariae might originate from young differentiating cercariae within the snail body (F. hepatica or from cercariae which died just after encystment (P. daubneyi. The use of regular temperature changes for snails infected with F. hepatica or P. daubneyi must be monitored carefully during collection of metacercariae to select completely formed cysts for infecting definitive hosts.

  12. Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute.

    Science.gov (United States)

    Gibson, Jeffrey B; Maxwell, Robert A; Schweitzer, John B; Fabian, Timothy C; Proctor, Kenneth G

    2002-03-01

    The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of 100 mmHg and a HR of CO2 reactivity was preserved with blood vs. saline (all P CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.

  13. Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs.

    Science.gov (United States)

    Bernstein, David I; Bravo, Fernando J; Pullum, Derek A; Shen, Hui; Wang, Mei; Rahman, Aquilur; Glazer, Robert I; Cardin, Rhonda D

    2015-02-01

    Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases. The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated. Treatment of the acute disease with N-methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N-methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water. N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Epstein-Barr virus in oral shedding of children with multiple sclerosis

    Science.gov (United States)

    Yea, Carmen; Tellier, Raymond; Chong, Patrick; Westmacott, Garrett; Marrie, Ruth Ann; Bar-Or, Amit

    2013-01-01

    Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS). Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry. Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS. Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV. PMID:24014504

  15. Porphyromonas gingivalis-mediated shedding of extracellular matrix metalloproteinase inducer (EMMPRIN) by oral epithelial cells: a potential role in inflammatory periodontal disease.

    Science.gov (United States)

    Feldman, Mark; La, Vu Dang; Lombardo Bedran, Telma Blanca; Palomari Spolidorio, Denise Madalena; Grenier, Daniel

    2011-12-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) or CD147 is a transmembrane glycoprotein expressed by various cell types, including oral epithelial cells. Recent studies have brought evidence that EMMPRIN plays a role in periodontitis. In the present study, we investigated the effect of Porphyromonas gingivalis, a major pathogen in chronic periodontitis, on the shedding of membrane-anchored EMMPRIN and on the expression of the EMMPRIN gene by oral epithelial cells. A potential contribution of shed EMMPRIN to the inflammatory process of periodontitis was analyzed by evaluating the effect of recombinant EMMPRIN on cytokine and matrix metalloproteinase (MMP) secretion by human gingival fibroblasts. ELISA and immunofluorescence analyses revealed that P. gingivalis mediated the shedding of epithelial cell-surface EMMPRIN in a dose- and time-dependent manner. Cysteine proteinase (gingipain)-deficient P. gingivalis mutants were used to demonstrate that both Arg- and Lys-gingipain activities are involved in EMMPRIN shedding. Real-time PCR showed that P. gingivalis had no significant effect on the expression of the EMMPRIN gene in epithelial cells. Recombinant EMMPRIN induced the secretion of IL-6 and MMP-3 by gingival fibroblasts, a phenomenon that appears to involve mitogen activated protein kinases. The present study brought to light a new mechanism by which P. gingivalis can promote the inflammatory response during periodontitis. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. High Shedding Potential and Significant Individual Heterogeneity in Naturally-Infected Alpine ibex (Capra ibex With Brucella melitensis

    Directory of Open Access Journals (Sweden)

    Sébastien Lambert

    2018-05-01

    Full Text Available Wildlife reservoirs of infectious diseases raise major management issues. In Europe, brucellosis has been eradicated in domestic ruminants from most countries and wild ruminants have not been considered important reservoirs so far. However, a high prevalence of Brucella melitensis infection has been recently identified in a French population of Alpine ibex (Capra ibex, after the emergence of brucellosis was confirmed in a dairy cattle farm and two human cases. This situation raised the need to identify the factors driving the persistence of Brucella infection at high prevalence levels in this ibex population. In the present paper, we studied the shedding pattern of B. melitensis in ibex from Bargy Massif, French Alps. Bacteriological examinations (1–15 tissues/samples per individual were performed on 88 seropositive, supposedly infected and euthanized individuals. Among them, 51 (58% showed at least one positive culture, including 45 ibex with at least one Brucella isolation from a urogenital sample or a lymph node in the pelvic area (active infection in organs in the pelvic area. Among these 45 ibex, 26 (30% of the total number of necropsied animals showed at least one positive culture for a urogenital organ and were considered as being at risk of shedding the bacteria at the time of capture. We observed significant heterogeneity between sex-and-age classes: seropositive females were most at risk to excrete Brucella before the age of 5 years, possibly corresponding to abortion during the first pregnancy following infection such as reported in the domestic ruminants. The high shedding potential observed in young females may have contributed to the self-sustained maintenance of infection in this population, whereas males are supposed to play a role of transmission between spatial units through venereal transmission during mating. This heterogeneity in the shedding potential of seropositive individuals should be considered in the future to

  17. The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

    International Nuclear Information System (INIS)

    Hollier, Mark J.; Dimmock, Nigel J.

    2005-01-01

    In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, β-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell

  18. Evaluation of a menstrual cup to collect shed endometrium for in vitro studies.

    Science.gov (United States)

    Koks, C A; Dunselman, G A; de Goeij, A F; Arends, J W; Evers, J L

    1997-09-01

    To evaluate whether a menstrual cup is a suitable instrument to collect antegradely shed endometrium for in vitro studies. A prospective, descriptive, cell biological and immunohistochemical study. Tertiary care university medical center. Nine female volunteers with regular cycles. Menstrual effluent was collected with a menstrual cup. Experience with the menstrual cup was described. Cytospin specimens, frozen sections, and cultures were prepared from the obtained menstrual tissue. The acceptability of the menstrual cup. The presence and viability of endometrial tissue was evaluated using immunohistochemical staining and culture outcome. All women except one described the menstrual cup as acceptable. Menstrual effluent contained single cells, clumps of cells, and glandlike structures. After 5 days of culture, the endometrial tissue appeared to be viable. Immunohistochemistry showed positive staining for vimentin in most cytospin specimens, in all cryostat specimens, and in 10 of 17 cultures. Cytokeratin 18 stained most cytospin specimens, all cryostat specimens, and 10 of 17 cultures. Positive staining for BW495/36 was observed in most cytospin specimens, all cryostat specimens, and 11 of 17 cultures. A menstrual cup in an acceptable instrument to collect antegradely shed menstrual tissue. Menstruum contains viable endometrial tissue that can be used for in vitro studies of endometrium and endometriosis.

  19. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects

    Directory of Open Access Journals (Sweden)

    Momoh Mambu

    2010-11-01

    Full Text Available Abstract Background Lassa hemorrhagic fever (LHF is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV GP1 (sGP1 in vitro resulting from the expression of the glycoprotein complex (GPC gene 12. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV, a filovirus that also causes hemorrhagic fever with nearly 90% fatality rates 345. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH Lassa Fever Ward (LFW, in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. Results It is reasonable to expect that a narrow window exists for

  20. Application of Hybrid Meta-Heuristic Techniques for Optimal Load Shedding Planning and Operation in an Islanded Distribution Network Integrated with Distributed Generation

    Directory of Open Access Journals (Sweden)

    Jafar Jallad

    2018-05-01

    Full Text Available In a radial distribution network integrated with distributed generation (DG, frequency and voltage instability could occur due to grid disconnection, which would result in an islanded network. This paper proposes an optimal load shedding scheme to balance the electricity demand and the generated power of DGs. The integration of the Firefly Algorithm and Particle Swarm Optimization (FAPSO is proposed for the application of the planned load shedding and under frequency load shedding (UFLS scheme. In planning mode, the hybrid optimization maximizes the amount of load remaining and improves the voltage profile of load buses within allowable limits. Moreover, the hybrid optimization can be used in UFLS scheme to identify the optimal combination of loads that need to be shed from a network in operation mode. In order to assess the capabilities of the hybrid optimization, the IEEE 33-bus radial distribution system and part of the Malaysian distribution network with different types of DGs were used. The response of the proposed optimization method in planning and operation were compared with other optimization techniques. The simulation results confirmed the effectiveness of the proposed hybrid optimization in planning mode and demonstrated that the proposed UFLS scheme is quick enough to restore the system frequency without overshooting in less execution time.

  1. A vortex-shedding flowmeter based on IPMCs

    International Nuclear Information System (INIS)

    Pasquale, Giovanna Di; Pollicino, Antonino; Graziani, Salvatore; Strazzeri, Salvatore

    2016-01-01

    Ionic polymer–metal composites (IPMCs) are electroactive polymers that can be used both as sensors and actuators. They have been demonstrated for many potential applications, in wet and underwater environments. Applications in fields such as biomimetics, robotics, and aerospace, just to mention a few, have been proposed. In this paper, the sensing nature of IPMCs is used to develop a flowmeter based on the vortex shedding phenomenon. The system is described, and a model is proposed and verified. A setup has been realized, and data have been acquired for many working conditions. The performance of the sensing system has been investigated by using acquired experimental data. Water flux velocities in the range [0.38, 2.83] m s −1 have been investigated. This working range is comparable with ranges claimed for established technologies. Results show the suitability of the proposed system to work as a flowmeter. The proposed transducer is suitable for envisaged post-silicon applications, where the use of IPMCs gives the opportunity to realize a new generating polymeric flowmeter. This has potential applications in fields where properties of IPMCs such as low cost, usability, and disposability are relevant. (paper)

  2. Application of Meta-Heuristic Techniques for Optimal Load Shedding in Islanded Distribution Network with High Penetration of Solar PV Generation

    Directory of Open Access Journals (Sweden)

    Mohammad Dreidy

    2017-01-01

    Full Text Available Recently, several environmental problems are beginning to affect all aspects of life. For this reason, many governments and international agencies have expressed great interest in using more renewable energy sources (RESs. However, integrating more RESs with distribution networks resulted in several critical problems vis-à-vis the frequency stability, which might lead to a complete blackout if not properly treated. Therefore, this paper proposed a new Under Frequency Load Shedding (UFLS scheme for islanding distribution network. This scheme uses three meta-heuristics techniques, binary evolutionary programming (BEP, Binary genetic algorithm (BGA, and Binary particle swarm optimization (BPSO, to determine the optimal combination of loads that needs to be shed from the islanded distribution network. Compared with existing UFLS schemes using fixed priority loads, the proposed scheme has the ability to restore the network frequency without any overshooting. Furthermore, in terms of execution time, the simulation results show that the BEP technique is fast enough to shed the optimal combination of loads compared with BGA and BPSO techniques.

  3. Association between nasal shedding and fever that influenza A (H3N2) induces in dogs.

    Science.gov (United States)

    Song, Daesub; Moon, Hyoungjoon; Jung, Kwonil; Yeom, Minjoo; Kim, Hyekwon; Han, Sangyoon; An, Dongjun; Oh, Jinsik; Kim, Jongman; Park, Bongkyun; Kang, Bokyu

    2011-01-05

    Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV) H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing) during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5 °C (geometric mean temperature of 39.86 °C ± 0.49) were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID₅₀/ml, which was significantly higher than the viral titer detected in the non fever. The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  4. Association between nasal shedding and fever that influenza A (H3N2 induces in dogs

    Directory of Open Access Journals (Sweden)

    Oh Jinsik

    2011-01-01

    Full Text Available Abstract Background Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. Methods An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. Results The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5°C (geometric mean temperature of 39.86°C±0.49 were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID50/ml, which was significantly higher than the viral titer detected in the non fever. Conclusions The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  5. A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy

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    Masese Linnet N

    2011-11-01

    Full Text Available Abstract Background Trichomonas vaginalis has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels. Methods We conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g. Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation. Results Among 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%], 4 (13% [95% CI 4% - 30%], and 5 (16% [95% confidence interval {CI} 5% - 34%] women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7. In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45, p = 0.6. Conclusion Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.

  6. Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico.

    Directory of Open Access Journals (Sweden)

    Leticia Ferreyra-Reyes

    Full Text Available Mexico introduced inactivated polio vaccine (IPV into its routine immunization (RI schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV twice a year during national health weeks (NHW through 2015.To evaluate individual variables associated with poliovirus (PV shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts.We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV and 144 household contacts (both genders, 2 per household, children and adults between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment. We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR.We estimated adjusted hazard ratios (HR and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection.216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142; PV1 in 1.2% (n = 29, PV2 in 4.1% (n = 103, and PV3 in 1.9% (n = 48. Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42, PV2 in 21.09% (n = 54, and PV3 in 23.05% (n = 59. Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with shedding of PV2 by a household contact. All models were

  7. Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico

    Science.gov (United States)

    Ferreyra-Reyes, Leticia; Cruz-Hervert, Luis Pablo; Troy, Stephanie B.; Huang, ChunHong; Sarnquist, Clea; Delgado-Sánchez, Guadalupe; Canizales-Quintero, Sergio; Holubar, Marisa; Ferreira-Guerrero, Elizabeth; Montero-Campos, Rogelio; Rodríguez-Álvarez, Mauricio; Mongua-Rodriguez, Norma; Maldonado, Yvonne

    2017-01-01

    Background Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015. Objectives To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts. Materials and methods We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment). We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR. Analysis We estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection. Results 216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in 4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09% (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with

  8. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Science.gov (United States)

    Dewji, Nazneen N; Singer, S Jonathan; Masliah, Eliezer; Rockenstein, Edward; Kim, Mihyun; Harber, Martha; Horwood, Taylor

    2015-01-01

    β-Amyloid (Aβ) accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD). Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP) and Presenilin (PS), as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  9. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nazneen N Dewji

    Full Text Available β-Amyloid (Aβ accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD. Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP and Presenilin (PS, as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  10. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

  11. A review of Sarcocystis spp. shed by opossums (Didelphis spp. in Brazil

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    Samantha Yuri Oshiro Branco Valadas

    2016-08-01

    Full Text Available South American opossums are the definitive hosts of Sarcocystis neurona, Sarcocystis falcatula, Sarcocystis speeri and Sarcocystis lindsayi. The sporocysts of these species of Sarcocystis are morphologically similar and methods like infectivity and pathogenicity for intermediate hosts (immunodeficient mice and psittacine birds and molecular tools are used for identification. Opossums are synanthropic wild animals, and widely distributed in Brazilian territory. Previous studies have shown high environmental contamination with S. neurona sporocysts in several Brazilian regions. This paper reviews information on Sarcocystis spp. shed by various opossum species and its occurrence in Brazil.

  12. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

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    Victor Chatterjee

    Full Text Available A disintegrin and metalloproteinase15 (ADAM15 has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS. An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3' UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.

  13. Coordinated Scheme of Under-Frequency Load Shedding with Intelligent Appliances in a Cyber Physical Power System

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    Qi Wang

    2016-08-01

    Full Text Available The construction of a cyber physical system in a power grid provides more potential control strategies for the power grid. With the rapid employment of intelligent terminal equipment (e.g., smart meters and intelligent appliances in the environment of a smart grid, abundant dynamic response information could be introduced to support a secure and stable power system. Combining demand response technology with the traditional under-frequency load shedding (UFLS scheme, a new UFLS strategy-determining method involving intelligent appliances is put forward to achieve the coordinated control of quick response resources and the traditional control resources. Based on this method, intelligent appliances can be used to meet the regulatory requirements of system operation in advance and prevent significant frequency drop, thereby improving the flexibility and stability of the system. Time-domain simulation verifies the effectiveness of the scheme, which is able to mitigate frequency drop and reduce the amount of load shedding.

  14. Response to a wild poliovirus type 2 (WPV2)-shedding event following accidental exposure to WPV2, the Netherlands, April 2017.

    Science.gov (United States)

    Duizer, Erwin; Ruijs, Wilhelmina Lm; van der Weijden, Charlie P; Timen, Aura

    2017-05-25

    On 3 April 2017, a wild poliovirus type 2 (WPV2) spill occurred in a Dutch vaccine manufacturing plant. Two fully vaccinated operators with risk of exposure were advised on stringent personal hygiene and were monitored for virus shedding. Poliovirus (WPV2-MEF1) was detected in the stool of one, 4 days after exposure, later also in sewage samples. The operator was isolated at home and followed up until shedding stopped 29 days after exposure. No further transmission was detected. This article is copyright of The Authors, 2017.

  15. Coordinated control of smart microgrid during and after islanding operation to prevent under frequency load shedding using energy storage system

    International Nuclear Information System (INIS)

    Koohi-Kamali, Sam; Rahim, Nasrudin Abd

    2016-01-01

    Highlights: • A new power management system is proposed. • The novel idea of using energy storage systems to prevent under frequency load shedding is presented. • A method to estimate rate of change of frequency in islanding mode and to dispatch battery plant is introduced. • Two effective outer control loops are proposed for governor to synchronize the microgrid with main grid. • Solar photovoltaic and battery plants bring the voltage regulation ancillary service for microgrid. - Abstract: This work presents a smart microgrid consisting of diesel, photovoltaic (PV), and battery storage plants. One of the key features of smart grid is to provide a redundant high quality power for the consumers. In islanded microgrid, the under frequency and/or voltage collapse, caused by power deficiency, can lead to power outage. The current practice is to shed the load demand until the frequency and voltage are restored. However, the redundancy in supplying power has no meaning as long as the loads are shed. The main objective of this paper is to propose a power management system (PMS) that protects the microgrid against the load shedding. PMS is able to control the microgrid in both centralized and decentralized fashions. To prevent under frequency load shedding (UFLS), this work proposes using battery energy storage system (BESS) to compensate for the power mismatch in the islanded microgrid. A method is presented to estimate the rate of change of frequency and to calculate the power deficiency. The approximated value is exploited as the set-point to dispatch BESS. PV and battery plants are supposed to share the reactive power demand proportionally and thus regulate the voltage at the load bus. This work also suggests two outer control loops, namely, frequency restoration loop (FRL) and difference angle compensator (DAC). These loops ensure microgrid smooth transition from islanded mode to grid-connected mode. The microgrid is configured to investigate the effective

  16. Renewable energy the best remedy for electrical load shedding in Pakistan

    International Nuclear Information System (INIS)

    Bhutta, S.M.

    2011-01-01

    Average 33% time of daily electrical load shedding in Pakistan is most serious as it has affected all activities. Industries are crippled, commercial, official activities and daily life is being deteriorated Total loss to Export is 1.3 and oil import bill is $ 9 Billion. If appropriate actions are not taken immediately; the situation is going to get worse when people will fight for every watt of electricity. The impounding crises are not foreseen and its gravity is not yet properly realized by the decision makers. Politics and several lobbies work against construction of major projects of hydel power and baseless controversies have been created. Pakistan is blessed with abundant renewable energy i.e. 2.9 million MW solar, tidal, wind 346,000 MW and 59,000 MW potentials of hydro electricity. Analysis of the reasons for the slow and no growth of these vital renewable potentials in Pakistan indicate that there are barriers which need to be mitigated to take immediate benefits to overcome menace of load shedding. Local R and D, Design, manufacturing, installation and feasibility study capabilities are negligible. Institutional capabilities in most of the organizations can at best be ranked as average or weak. Other impediments and barriers that continue to hamper the load shedding are losses, attitude in the promotion of renewable and hydro power projects include: lack of serious attempts to mitigate the barriers, integrate the programs with profitability; inadequate evaluation of resources; non availability of reliable baseline data; and lack of coordination among the relevant agencies; weak institutional arrangements for renewable energy promotion; absence of fiscal and financing mechanisms; lack of understanding, awareness, information and outreach; uneven allocation of resources; lack of appropriate quality management, monitoring and evaluation programs; and need of attractive policy framework and legislative support, building consensus among people and provinces

  17. Patterns of faecal nematode egg shedding after treatment of sheep with a long-acting formulation of moxidectin.

    Science.gov (United States)

    Crilly, James Patrick; Jennings, Amy; Sargison, Neil

    2015-09-15

    Much of the current information on the effects of long-acting anthelmintics on nematode populations derives either from research farms or mathematical models. A survey was performed with the aim of establishing how moxidectin is currently being used on sheep farms in the south-east of Scotland. A study was undertaken on a subsection of the surveyed farms to examine the effects of long-acting moxidectin treatments in both spring and autumn on faecal nematode egg output. The survey showed that whole flock treatments of injectable 2% moxidectin were used to control sheep scab on 21% of farms. Injectable 2% moxidectin and oral moxidectin were used to control the periparturient rise in faecal nematode egg shedding by ewes on 13% and 55% of farms respectively. The effects of injectable 2% moxidectin treatment on faecal nematode egg shedding post-treatment in both the autumn and spring were investigated by faecal nematode egg counts at the time of treatment and at 2-weekly interval thereafter on eight and six farms in the autumn and spring, respectively. Faecal egg shedding recommenced at 8 weeks (autumn) and 4 weeks (spring) post-treatment. Counts increased to a peak and then declined. The mean (95% confidence interval) peak counts post-treatment were 2.8 (0.6, 5.1), 3.6 (1.7, 5.5) and 53.5 (25.1, 82.0) eggs per gram (EPG) for autumn-treated ewes, autumn-treated lambs and spring-treated ewes respectively. The spring treated sheep showed a statistically significantly earlier return to faecal egg shedding (p=0.0125, p=0.0342) compared to both other groups, statistically significantly higher peak in egg counts than the autumn treated sheep (pegg counts (p=0.0148). There was no statistically significant difference in the timing of the peak FECs between autumn and spring (p=0.211). The FECs of all groups of sheep treated with an injectable long-acting formulation of moxidectin became positive earlier than would be expected from the period of persistence given on the datasheet

  18. Deposit Shedding in Biomass-Fired Boilers: Shear Adhesion Strength Measurements

    DEFF Research Database (Denmark)

    Laxminarayan, Yashasvi; Jensen, Peter Arendt; Wu, Hao

    2017-01-01

    Ash deposition on boiler surfaces is a major problem encountered in biomass combustion. Timely removal of ash deposits is essentialfor optimal boiler operation. In order to improve the understanding of deposit shedding in boilers, this study investigates the adhesion strength of biomass ash from...... off by an electrically controlled arm, and the corresponding adhesion strength was measured. The effect of sintering temperature, sintering time, deposit composition, thermal shocks on the deposit, and steel type was investigated. The results reveal that the adhesion strength of ash deposits...... is dependent on two factors: ash melt fraction, and corrosion occurring at the deposit–tube interface. Adhesion strength increases with increasing sintering temperature, sharply increasing at the ash deformation temperature. However, sintering time, as well as the type of steel used, does not have...

  19. Replication kinetics and shedding of very virulent Marek's disease virus and vaccinal Rispens/CVI988 virus during single and mixed infections varying in order and interval between infections.

    Science.gov (United States)

    Islam, Tanzila; Walkden-Brown, Stephen W; Renz, Katrin G; Islam, A F M Fakhrul; Ralapanawe, Sithara

    2014-10-10

    Vaccination is thought to contribute to an evolution in virulence of the Marek's disease virus (MDV) as vaccines prevent disease but not infection. We investigated the effects of co-infections at various intervals between Rispens/CVI988 vaccine virus (Rispens) and very virulent MDV (vvMDV) on the replication and shedding of each virus. The experiment used 600 ISA Brown layer chickens in 24 isolators with all treatments replicated in two isolators. Chickens were vaccinated with Rispens and/or challenged with the vvMDV isolate 02LAR on days 0, 5, or 10 post hatching providing vaccination to challenge intervals (VCI) of -10, -5, 0, 5 or 10 days with the negative values indicating challenge prior to vaccination. Peripheral blood lymphocytes (PBL), feathers and isolator exhaust dust were sampled between 7 and 56 days post infection (dpi) and subjected to quantitative real-time polymerase chain reaction (qPCR) to differentiate the two viruses. Overall Rispens significantly reduced the viral load of vvMDV in PBL and feather cells and shedding in dust. Similarly vvMDV significantly reduced the viral load of Rispens in PBL and feather cells but not in dust. VCI significantly influenced these relationships having strong positive and negative associations with load of vvMDV and Rispens respectively. Differences between the two viruses and their effects on each other were greatest in PBL and feathers, and least in dust. This study expands our understanding of the interaction between pathogenic and vaccinal viruses following vaccination with imperfect vaccines and has implications for selection of appropriate samples to test for vaccination success. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Goats may experience reproductive failures and shed Coxiella burnetii at two successive parturitions after a Q fever infection.

    Science.gov (United States)

    Berri, M; Rousset, E; Champion, J L; Russo, P; Rodolakis, A

    2007-08-01

    Q fever is a zoonosis caused by the obligate intracellular bacterium, Coxiella burnetii. Aborting domestic ruminants are the main source of human infection. In January 2003, an abortion episode occurred in a dairy caprine herd where 18/60 (30%) goats experienced reproductive problems: 4/60 (7%) aborted and 14/60 (23%) had stillbirths. Serological screening for abortion-related infectious diseases suggested Q fever. The diagnosis of C. burnetii infection was confirmed with PCR based on the occurrence of C. burnetii shedding into vaginal mucus, faeces and colostrums taken after kidding from the affected animals. The pregnancy following this episode resulted in one abortion and four stillbirths; three of those goats had already experienced reproductive failure during the previous kidding season. The seroprevalence of C. burnetii infection and the bacteria shedding were investigated using both ELISA and PCR assays, respectively, during the course of the initial and subsequent kidding seasons. Serological testing, performed on the whole herd 6 weeks after the abortion episode, showed 48/60 (80%) of ELISA positive goats. PCR assay performed on both vaginal swab and milk samples showed that the bacterium was shed for almost four months after the outbreak. C. burnetii DNA was also amplified from vaginal swab and milk samples taken from goats after the second kidding season. Furthermore, the bacteria were found into 14 vaginal swabs and 12 milk samples taken from infected females at both kidding seasons.

  1. Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea.

    Science.gov (United States)

    Bin, Seo Yu; Heo, Jung Yeon; Song, Min-Suk; Lee, Jacob; Kim, Eun-Ha; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Se Mi; Kim, Young-Il; Si, Young-Jae; Lee, In-Won; Baek, Yun Hee; Choi, Won-Suk; Min, Jinsoo; Jeong, Hye Won; Choi, Young Ki

    2016-03-15

    Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients' respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. The seroprevalence and salivary shedding of herpesviruses in Behçet's syndrome and recurrent aphthous stomatitis

    Directory of Open Access Journals (Sweden)

    Noha Seoudi

    2015-06-01

    Full Text Available Background: Behçet's syndrome (BS is one of the multisystemic diseases that presents with oral ulceration and several other systemic manifestations including genital ulceration, folliculitis, erythema nodosum-like lesions, uveitis, and arthropathy. Ocular manifestation, central nervous system involvement, and gastrointestinal manifestation account for most of the complications of this disease, whereas orogenital ulceration and dermatological involvement affects the quality of life. The cause of the disease is not fully elucidated; however, herpesviruses have long been thought to play a pivotal role in the disease pathogenesis. Objective: To investigate the seroprevalence and salivary shedding of herpesviruses in BS. Method: The levels of specific immunoglobulin G in six different herpesviruses in serum samples collected from 54 BS, 28 healthy controls (HC, and 7 recurrent aphthous stomatitis (RAS patients were investigated. Salivary viral load was also quantified for these viruses in matched saliva samples using quantitative real-time polymerase chain reaction. Results: The BS had lower cytomegalovirus (CMV IgG level in comparison to HC (p=0.0226 and RAS (p=0.0450. There was statistically significant higher salivary shedding of Epstein-Barr virus (EBV in BS in comparison to HC (p=0.0052, but not RAS (p=0.3318. Conclusions: A high EBV shedding was observed in both BS and RAS and a lower level of CMV IgG was observed in BS only. The reason for the observed lower level of CMV IgG in BS is not clear. However, one explanation might be a defect in the cross-talk between innate and adaptive immune responses which was suggested by a previously described defect in the toll-like receptor 1 and 2 heterodimer formation and function, this being the initial receptor sensing of CMV.

  3. Effect of longitudinal and transverse vibrations of an upstream square cylinder on vortex shedding behind two inline square cylinders

    International Nuclear Information System (INIS)

    Patil, Pratish P; Tiwari, Shaligram

    2009-01-01

    The characteristics of unsteady wakes behind a stationary square cylinder and another upstream vibrating square cylinder have been investigated numerically with the help of a developed computational code. The effect of longitudinal as well as transverse vibrations of the upstream cylinder is studied on the coupled wake between the two cylinders, which is found to control the vortex shedding behavior behind the downstream stationary cylinder. Computations are carried out for a fixed value of Reynolds number (Re = 200) and three different values of excitation frequencies of the upstream cylinder, namely less than, equal to and greater than the natural frequency of vortex shedding corresponding to flow past a stationary square cylinder. The vortex shedding characteristics of the unsteady wakes behind the vibrating and stationary cylinders are found to differ significantly for longitudinal and transverse modes of vibration of the upstream cylinder. The wake of the downstream stationary cylinder is found to depict a synchronization behavior with the upstream cylinder vibration. The spacing between the two cylinders has been identified to be the key parameter influencing the synchronization phenomenon. The effect of cylinder spacing on the wake synchronization and the hydrodynamic forces has been examined. In addition, a comparison of the drag forces for flow past transversely vibrating square and circular cylinders for similar amplitudes and frequencies of cylinder vibration has been presented while employing the tested computational code.

  4. Quantification and determinants of the amount of respiratory syncytial virus (RSV shed using real time PCR data from a longitudinal household study [version 2; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Miriam Wathuo

    2017-03-01

    Full Text Available Background A better understanding of respiratory syncytial virus (RSV epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2 log10 ribonucleic acid (RNA copies * days. Young age (<1 year, presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

  5. Simulated browsing affects leaf shedding phenology and litter quality of oak and birch saplings

    OpenAIRE

    Palacio, Sara; Hester, A. J.; Maestro Martínez, Melchor; Millard, P.

    2013-01-01

    Herbivore effects on leaf litter can have a strong impact on ecosystem nutrient cycling. Although such effects are well described for insect herbivory, research on the impacts of browsing by mammalian herbivores on leaf litter dynamics and nutrient cycling has been more limited, particularly at the level of the individual plant. Clipping treatments (66% shoot removal twice, plus unclipped) were applied to analyse the effect of browsing on the phenology (start date and pattern of leaf shedding...

  6. Adaptive Tuning of Frequency Thresholds Using Voltage Drop Data in Decentralized Load Shedding

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Faria Da Silva, Filipe Miguel; Bak, Claus Leth

    2015-01-01

    Load shedding (LS) is the last firewall and the most expensive control action against power system blackout. In the conventional under frequency LS (UFLS) schemes, the load drop locations are already determined independently of the event location. Furthermore, the frequency thresholds of LS relays...... are prespecified and constant values which may not be a comprehensive solution for widespread range of possible events. This paper addresses the decentralized LS in which the instantaneous voltage deviation of load buses is used to determine the frequency thresholds of LS relays. The higher frequency thresholds...

  7. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

    Directory of Open Access Journals (Sweden)

    Nicola Lehners

    Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  8. Wide-range vortex shedding flowmeter for high-temperature helium gas

    Energy Technology Data Exchange (ETDEWEB)

    Baker, S.P.; Herndon, P.G.; Ennis, R.M. Jr.

    1983-01-01

    The existing design of a commercially available vortex shedding flowmeter (VSFM) was modified and optimized to produce three 4-in. and one 6-in. high-performance VSFMs for measuring helium flow in a gas-cooled fast reactor (GCFR) test loop. The project was undertaken because of the significant economic and performance advantages to be realized by using a single flowmeter capable of covering the 166:1 flow range (at 350/sup 0/C and 45:1 pressure range) of the tests. A detailed calibration in air and helium at the Colorado Engineering Experiment Station showed an accuracy of +-1% of reading for a 100:1 helium flow range and +-1.75% of reading for a 288:1 flow range in both helium and air. At an extended gas temperature of 450/sup 0/C, water cooling was necessary for reliable flowmeter operation.

  9. Shedding light on restoring respiratory function after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Warren J Alilain

    2009-10-01

    Full Text Available Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following SCI - including pharmacological and regeneration strategies. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental spinal cord injury. We also discuss how such light induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.

  10. Increased shedding of microvesicles from intimal smooth muscle cells in athero-prone areas of the human aorta: implications for understanding of the predisease stage.

    Science.gov (United States)

    Bobryshev, Yuri V; Killingsworth, Murray C; Orekhov, Alexander N

    2013-01-01

    This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage. Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta. The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001). The present study supports the concept that alterations of the arterial intima occur at the predisease stage. Copyright © 2012 S. Karger AG, Basel.

  11. Subclinical Shed of Infectious Varicella zoster Virus in Astronauts

    Science.gov (United States)

    Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.

    2007-01-01

    Aerosol borne varicella zoster virus (VZV) enters the nasopharynx and replicates in tonsillar T-cells, resulting in viremia and varicella (chickenpox). Virus then becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis (1). Decades later, as cell-mediated immunity to VZV declines (4), latent VZV can reactivate to produce zoster (shingles). Infectious VZV is present in patients with varicella or zoster, but shed of infectious virus in the absence of disease has not been shown. We previously detected VZV DNA in saliva of astronauts during and shortly after spaceflight, suggesting stress induced subclinical virus reactivation (3). We show here that VZV DNA as well as infectious virus in present in astronaut saliva. VZV DNA was detected in saliva during and after a 13-day spaceflight in 2 of 3 astronauts (Fig. panel A). Ten days before liftoff, there was a rise in serum anti-VZV antibody in subjects 1 and 2, consistent with virus reactivation. In subject 3, VZV DNA was not detected in saliva, and there was no rise in anti-VZV antibody titer. Subject 3 may have been protected from virus reactivation by having zoster DNA was detected in astronaut saliva months before spaceflight, or in saliva of 10 age/sex-matched healthy control subjects sampled on alternate days for 3 weeks (88 saliva samples). Saliva taken 2-6 days after landing from all 3 subjects was cultured on human fetal lung cells (Fig. panel B). Infectious VZV was recovered from saliva of subjects 1 and 2 on the second day after landing. Virus specificity was confirmed by antibody staining and DNA analysis which showed it to be VZV of European descent, common in the US (5). Further, both antibody staining and DNA PCR demonstrated that no HSV-1 was detected in any infected culture. This is the first report of infectious VZV shedding in the absence of clinical disease. Spaceflight presents a uniquely stressful environment which includes physical isolation and

  12. A comparative analysis on the shed vortices from the wake of finned, foam-wrapped cylinders

    Energy Technology Data Exchange (ETDEWEB)

    Khashehchi, Morteza [Department of Agro-Technology, College of Aburaihan, University of Tehran, Tehran (Iran, Islamic Republic of); Ashtiani Abdi, Iman; Hooman, Kamel, E-mail: m.khashehchi@ut.ac.ir [School of Mechanical and mining Engineering, University of Queensland, Brisbane (Australia)

    2017-08-15

    The wake characteristics behind a finned and a foam-wrapped circular cylinder has been compared in a study (Khashehchi et al 2014 Exp. Therm. Fluid Sci. 52 328–38) done by the Authors. In this paper, the shed vortices from the wake of the same cylinders have been studied. Shedding in a bluff body has an important effect on increasing the pressure drop downstream of the object. Here, we have used particle image velocimetry to investigate the detached vortices from the wake behind a foam-wrapped and a finned cylinder. The standard case of cross-flow over a bare cylinder, i.e. no surface extension, has also been tested as a benchmark. The experiments have been performed for Reynolds numbers 2000 based on the mean air velocity and the cylinder’s outer diameter. To identify the features of each aforementioned case, linear stochastic estimation has been applied to the velocity fields. Results show that unlike the fin, adding foam to the cylinder surface increases the size of detached vortices and amplifies the core strength. Moreover, foam-wrapped cylinder in contrast to the finned one produces strong three-dimensionality. Interestingly, finned cylinder’s results show less three-dimensionality compared to the bare cylinder. (paper)

  13. The kinetics of oocyst shedding and sporulation in two immunologically distinct strains of Eimeria maxima, GS and M6.

    Science.gov (United States)

    Al-Badri, Riadh; Barta, John Robert

    2012-11-01

    The kinetics of oocyst shedding and sporulation of two immunologically distinct strains of Eimeria maxima (GS and M6) were compared. Both strains had a prepatent period of approximately 120 h followed by peak oocyst shedding at 144-150 h post inoculation. Mean total oocyst output determined for each strain demonstrated that the fecundity of the M6 strain (12.8 × 10(3) ± 1.95) of E. maxima was roughly twice that of the GS strain (6.9 × 10(3) ± 3.33) when inoculated at the rate of 1,000 infective oocysts per bird. The process of oocyst sporulation was followed by repetitive sampling of sporulating oocysts at 26 °C with aeration over a 138 hour period. Sporulation was divided into five morphologically distinguishable stages whose abundance peaked at the following times during sporulation: unsporulated oocysts at 0 h; sporoblast anlagen at 18 h; sporoblasts without sporocyst walls at 22 h; and sporocysts without mature sporozoites at 38 h. The time to 50 % sporulation of E. maxima oocysts observed in the present study was approximately 53 h for both strains and all viable oocysts had completed sporulation by 60 h. In the present study, the prepatent periods, duration of oocyst shedding, and the relative kinetics of sporulation of the GS and M6 strains of E. maxima were found to be virtually identical despite the immunological distinctiveness of these two parasite strains.

  14. CHILDREN'S RESIDENTIAL EXPOSURE TO CHLORPYRIFOS: APPLICATION OF CPPAES FIELD MEASUREMENTS OF CHLORPYRIFOS AND TCPY WITHIN MENTOR/SHEDS PESTICIDES MODEL

    Science.gov (United States)

    The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, howev...

  15. Shedding Light on Eco-Innovation in Tourism: A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Maria-del-Mar Alonso-Almeida

    2016-12-01

    Full Text Available The recent global increase in the competitiveness of tourism has made the implementation of eco-innovations a differentiating element among both the destinations and companies in the sector, with quality management and contribution to sustainable development being increasingly valued. However, the eco-innovations that have been developed and implemented in tourist industries have rarely been studied. In this study, the eco-innovations that have been developed and implemented by 57 tourism businesses worldwide are analysed. The identified eco-innovations are classified by using different qualitative methodologies. The obtained results shed light on the limited development of eco-innovations in the tourism industry and the industry focuses mainly on product eco-innovations. Several examples by the tourist sub-industry and types of eco-innovation are analysed. Furthermore, this study provides practical information about measures that both businesses and governmental organisations can adopt to promote eco-innovation in the sector.

  16. Evaluation of bovine coronavirus antibody levels, virus shedding, and respiratory disease incidence throughout the beef cattle production cycle

    Science.gov (United States)

    Objective- Determine how levels of serum antibody to bovine coronavirus (BCV) are related to virus shedding patterns and respiratory disease incidence in beef calves at various production stages. Animals- 890 crossbred beef calves from four separately managed herds at the U.S. Meat Animal Research C...

  17. Cessation of clinical disease and spirochete shedding after tiamulin treatment in pigs experimentally infected with "Brachyspira hampsonii".

    Science.gov (United States)

    Wilberts, B L; Arruda, P H; Warneke, H L; Erlandson, K R; Hammer, J M; Burrough, E R

    2014-10-01

    With the emergence of "Brachyspira hampsonii" associated with swine dysentery in North America, identification of effective treatments and interventions is a pressing need. Denagard® (tiamulin hydrogen fumarate) Liquid Concentrate 12.5% is approved in the United States for treatment of dysentery caused by Brachyspira hyodysenteriae at 0.006% in the water. In this study, the effectiveness of tiamulin in resolving clinical disease, eliminating viable spirochete shedding, and reducing neutrophilic colitis following infection with either "B. hampsonii" or B. hyodysenteriae was evaluated. Seventy-eight 7-week-old crossbred pigs were divided into three groups [sham-inoculated (n = 18), "B. hampsonii"-inoculated (n = 30), and B. hyodysenteriae-inoculated (n = 30)]. Each inoculum group was divided into three subgroups which received either 0.006% tiamulin, 0.018% tiamulin, or no medication. Both levels of tiamulin resolved clinical disease within 24 h of treatment initiation, eliminated spirochete shedding within 72 h of treatment initiation, and resolved and/or prevented histologic lesions in pigs infected with either Brachyspira spp. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Large-Eddy Simulation of turbulent vortex shedding

    International Nuclear Information System (INIS)

    Archambeau, F.

    1995-06-01

    This thesis documents the development and application of a computational algorithm for Large-Eddy Simulation. Unusually, the method adopts a fully collocated variable storage arrangement and is applicable to complex, non-rectilinear geometries. A Reynolds-averaged Navier-Stokes algorithm has formed the starting point of the development, but has been modified substantially: the spatial approximation of convection is effected by an energy-conserving central-differencing scheme; a second-order time-marching Adams-Bashforth scheme has been introduced; the pressure field is determined by solving the pressure-Poisson equation; this equation is solved either by use of preconditioned Conjugate-Gradient methods or with the Generalised Minimum Residual method; two types of sub-grid scale models have been introduced and examined. The algorithm has been validated by reference to a hierarchy of unsteady flows of increasing complexity starting with unsteady lid-driven cavity flows and ending with 3-D turbulent vortex shedding behind a square prism. In the latter case, for which extensive experimental data are available, special emphasis has been put on examining the dependence of the results on mesh density, near-wall treatment and the nature of the sub-grid-scale model, one of which is an advanced dynamic model. The LES scheme is shown to return time-average and phase-averaged results which agree well with experimental data and which support the view that LES is a promising approach for unsteady flows dominated by large periodic structures. (author)

  19. Large-Eddy Simulation of turbulent vortex shedding

    Energy Technology Data Exchange (ETDEWEB)

    Archambeau, F

    1995-06-01

    This thesis documents the development and application of a computational algorithm for Large-Eddy Simulation. Unusually, the method adopts a fully collocated variable storage arrangement and is applicable to complex, non-rectilinear geometries. A Reynolds-averaged Navier-Stokes algorithm has formed the starting point of the development, but has been modified substantially: the spatial approximation of convection is effected by an energy-conserving central-differencing scheme; a second-order time-marching Adams-Bashforth scheme has been introduced; the pressure field is determined by solving the pressure-Poisson equation; this equation is solved either by use of preconditioned Conjugate-Gradient methods or with the Generalised Minimum Residual method; two types of sub-grid scale models have been introduced and examined. The algorithm has been validated by reference to a hierarchy of unsteady flows of increasing complexity starting with unsteady lid-driven cavity flows and ending with 3-D turbulent vortex shedding behind a square prism. In the latter case, for which extensive experimental data are available, special emphasis has been put on examining the dependence of the results on mesh density, near-wall treatment and the nature of the sub-grid-scale model, one of which is an advanced dynamic model. The LES scheme is shown to return time-average and phase-averaged results which agree well with experimental data and which support the view that LES is a promising approach for unsteady flows dominated by large periodic structures. (author) 87 refs.

  20. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients

    DEFF Research Database (Denmark)

    Rahbar, Elaheh; Cardenas, Jessica C; Baimukanova, Gyulnar

    2015-01-01

    of trauma patients. METHODS: Plasma samples were collected from 5 healthy consented volunteers and 22 severely injured trauma patients upon admission to the emergency department. ELISA assays were performed to quantify shed HA, HS, CS and syndecan-1 in plasma. A colloid osmometer and Electric Cell......-substrate Impedance Sensing (ECIS) system were used to measure plasma colloid osmotic pressure (COP) and cell permeability, respectively. Thrombin generation was measured using a calibrated automated thrombogram (CAT). Initial vital signs, routine laboratory values, and injury severity scores (ISS) were recorded. Non......COP (≤16 mmHg) had significantly increased syndecan-1 and HA compared to those with normal COP, which corresponded to increased cell permeability via ECIS. CS and HS did not vary between COP groups. Lastly, patients with low COP displayed reduced peak thrombin...

  1. The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men

    Directory of Open Access Journals (Sweden)

    Young Myles D

    2010-11-01

    Full Text Available Abstract Background Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men. Methods and Design The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m2; no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II and randomised to one of three groups: (1 SHED-IT Resources - provision of materials (DVD, handbooks, pedometer, tape measure with embedded behaviour change strategies to support weight loss; (2 SHED-IT Online - same materials as SHED-IT Resources plus access to and instruction on how to use the study website; (3 Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome, % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary

  2. Shack-Hartmann Electron Densitometer (SHED): An Optical System for Diagnosing Free Electron Density in Laser-Produced Plasmas

    Science.gov (United States)

    2016-11-01

    Free Electron Density in Laser-Produced Plasmas by Anthony R Valenzuela Approved for public release; distribution is...AND SUBTITLE Shack-Hartmann Electron Densitometer (SHED): An Optical System for Diagnosing Free Electron Density in Laser-Produced Plasmas 5a...SUPPLEMENTARY NOTES 14. ABSTRACT The Shack-Hartmann Electron Densitometer is a novel method to diagnose ultrashort pulse laser–produced plasmas

  3. Shed vortex structure and phase-averaged velocity statistics in symmetric/asymmetric turbulent flat plate wakes

    Science.gov (United States)

    Rai, Man Mohan

    2018-05-01

    The near wake of a flat plate is investigated via direct numerical simulations. Many earlier experimental investigations have used thin plates with sharp trailing edges and turbulent boundary layers to create the wake. This results in large θ/DTE values (θ is the boundary layer momentum thickness toward the end of the plate and DTE is the trailing edge thickness). In the present study, the emphasis is on relatively thick plates with circular trailing edges (CTEs) resulting in θ/D values less than one (D is the plate thickness and the diameter of the CTE) and vigorous vortex shedding. The Reynolds numbers based on the plate length and D are 1.255 × 106 and 10 000, respectively. Two cases are computed: one with turbulent boundary layers on both the upper and lower surfaces of the plate (statistically the same, symmetric wake, Case TT) and the other with turbulent and laminar boundary layers on the upper and lower surfaces, respectively (asymmetric case, Case TL). The data and understanding obtained are of considerable engineering interest, particularly in turbomachinery where the pressure side of an airfoil can remain laminar or transitional because of a favorable pressure gradient and the suction side is turbulent. Shed-vortex structure and phase-averaged velocity statistics obtained in the two cases are compared here. The upper negative shed vortices in Case TL (turbulent separating boundary layer) are weaker than the lower positive ones (laminar separating boundary layer) at inception (a factor of 1.27 weaker in terms of peak phase-averaged spanwise vorticity at the first appearance of a peak). The upper vortices weaken rapidly as they travel downstream. A second feature of interest in Case TL is a considerable increase in the peak phase-averaged, streamwise normal intensity (random component) with increasing streamwise distance (x/D) that occurs near the positive vortex cores. This behavior is observed for a few diameters in the near wake. This is counter to

  4. Crystal Structure of the LasA Virulence Factor from Pseudomonas aeruginosa: Substrate Specificity and Mechanism of M23 Metallopeptidases

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, James; Murphy, Loretta M.; Conners, Rebecca; Sessions, Richard B.; Gamblin, Steven J. (Wales); (Bristol Med Sci); (NIMR)

    2010-09-21

    Pseudomonas aeruginosa is an opportunist Gram-negative bacterial pathogen responsible for a wide range of infections in immunocompromized individuals and is a leading cause of mortality in cystic fibrosis patients. A number of secreted virulence factors, including various proteolytic enzymes, contribute to the establishment and maintenance of Pseudomonas infection. One such is LasA, an M23 metallopeptidase related to autolytic glycylglycine endopeptidases such as Staphylococcus aureus lysostaphin and LytM, and to DD-endopeptidases involved in entry of bacteriophage to host bacteria. LasA is implicated in a range of processes related to Pseudomonas virulence, including stimulating ectodomain shedding of the cell surface heparan sulphate proteoglycan syndecan-1 and elastin degradation in connective tissue. Here we present crystal structures of active LasA as a complex with tartrate and in the uncomplexed form. While the overall fold resembles that of the other M23 family members, the LasA active site is less constricted and utilizes a different set of metal ligands. The active site of uncomplexed LasA contains a five-coordinate zinc ion with trigonal bipyramidal geometry and two metal-bound water molecules. Using these structures as a starting point, we propose a model for substrate binding by LasA that explains its activity against a wider range of substrates than those used by related lytic enzymes, and offer a catalytic mechanism for M23 metallopeptidases consistent with available structural and mutagenesis data. Our results highlight how LasA is a structurally distinct member of this endopeptidase family, consistent with its activity against a wider range of substrates and with its multiple roles in Pseudomonas virulence.

  5. Fabrication of Micromixers Utilizing Shedding Effect Induced by Electrokinetic Instability

    International Nuclear Information System (INIS)

    Fu, L-M; Tai, C-H; Tsai, C-H; Lin, C-H; Lee, C-Y

    2006-01-01

    This paper proposes a T-shaped micromixer featuring 45 deg. parallelogram barriers within the mixing channel. The proposed device obtains a rapid mixing of two sample fluids by means of the electrokinetic instability induced by shedding effect which is produced as an appropriate intensity of DC electric field of is applied. The proposed device uses a single high-voltage power source to simultaneously drive and mix the sample fluids. The effectiveness of the mixer is characterized experimentally as a function of the applied electrical field intensity and the extent to which the parallelogram barriers obstruct the mixing channel. The experimental results indicate that the mixing performance reaches 91.2% at a cross-section located 2.3 mm downstream of the T-junction when the barriers obstruct four-fifths of the channel width and an electrical field of 300V/cm is applied. The micromixing method presented in this study provides a simple low-cost solution to mixing problems in lab-on-a-chip systems

  6. MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Mark Niedringhaus

    Full Text Available Matrix metalloproteinases (MMPs are zinc-dependent endopeptidases that are released from neurons in an activity dependent manner. Published studies suggest their activity is important to varied forms of learning and memory. At least one MMP can stimulate an increase in the size of dendritic spines, structures which represent the post synaptic component for a large number of glutamatergic synapses. This change may be associated with increased synaptic glutamate receptor incorporation, and an increased amplitude and/or frequency of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA mini excitatory post-synaptic currents (EPSCs. An associated increase in the probability of action potential occurrence would be expected. While the mechanism(s by which MMPs may influence synaptic structure and function are not completely understood, MMP dependent shedding of specific cell adhesion molecules (CAMs could play an important role. CAMs are ideally positioned to be cleaved by synaptically released MMPs, and shed N terminal domains could potentially interact with previously unengaged integrins to stimulate dendritic actin polymerization with spine expansion. In the present study, we have used multielectrode arrays (MEAs to investigate MMP and soluble CAM dependent changes in neuronal activity recorded from hippocampal cultures. We have focused on intercellular adhesion molecule-5 (ICAM-5 in particular, as this CAM is expressed on glutamatergic dendrites and shed in an MMP dependent manner. We show that chemical long-term potentiation (cLTP evoked changes in recorded activity, and the dynamics of action potential bursts in particular, are altered by MMP inhibition. A blocking antibody to β(1 integrins has a similar effect. We also show that the ectodomain of ICAM-5 can stimulate β(1 integrin dependent increases in spike counts and burst number. These results support a growing body of literature suggesting that MMPs have important effects on neuronal

  7. New perspectives to the enterotoxigenic E. coli F4 porcine infection model: Susceptibility genotypes in relation to performance, diarrhoea and bacterial shedding.

    Science.gov (United States)

    Roubos-van den Hil, Petra J; Litjens, Ralph; Oudshoorn, Anna-Katharina; Resink, Jan Willem; Smits, Coen H M

    2017-04-01

    Enterotoxigenic E. coli (ETEC), causing post-weaning diarrhoea, is a major problem in weaned piglets. Individual animal responses to ETEC infection show high variability in animal experiments. Two studies were designed to optimize the ETEC F4ac infection model in piglets by combining the genotype susceptibility with performance, diarrhoea incidence and bacterial shedding. The studies were performed with respectively 120 and 80 male piglets that were tested for susceptibility or resistance towards ETEC O149:F4ac by a DNA marker based test. Three different genotypes were observed; resistant (RR), susceptible heterozygote (RS) and susceptible homozygote (SS). Piglets, were orally infected with an inoculum suspension (containing 1.5E8 CFU/ml ETEC F4ac) at day 0, 1 and 2 of the study. Performance, diarrhoea incidence and bacterial shedding were followed for 21days. In the first week after challenge a difference in average daily gain was observed between resistant and susceptible piglets in both studies. For the complete study period no significant differences were observed. Diarrhoea incidence was significantly higher in susceptible pigs compared to the resistant pigs in the first week after challenge. Bacterial shedding was much higher in the susceptible pigs and ETEC excretion lasted longer. ETEC was hardly detected in the faecal material of the resistant pigs. In conclusion, susceptible pigs showed higher diarrhoea incidence and higher numbers of faecal ETEC shedding in the first week after challenge compared to resistant pigs. The DNA marker based test can be used to select pigs that are susceptible for ETEC for inclusion in ETEC infection model, resulting in less animals needed to perform infection studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses.

    Science.gov (United States)

    Spickler, Anna R; Trampel, Darrell W; Roth, James A

    2008-12-01

    Some avian influenza viruses may be transmissible to mammals by ingestion. Cats and dogs have been infected by H5N1 avian influenza viruses when they ate raw poultry, and two human H5N1 infections were linked to the ingestion of uncooked duck blood. The possibility of zoonotic influenza from exposure to raw poultry products raises concerns about flocks with unrecognized infections. The present review examines the onset of virus shedding and the development of clinical signs for a variety of avian influenza viruses in chickens. In experimentally infected birds, some high-pathogenicity avian influenza (HPAI) and low-pathogenicity avian influenza (LPAI) viruses can occur in faeces and respiratory secretions as early as 1 to 2 days after inoculation. Some HPAI viruses have also been found in meat 1 day after inoculation and in eggs after 3 days. There is no evidence that LPAI viruses can be found in meat, and the risk of their occurrence in eggs is poorly understood. Studies in experimentally infected birds suggest that clinical signs usually develop within a few days of virus shedding; however, some models and outbreak descriptions suggest that clinical signs may not become evident for a week or more in some H5 or H7 HPAI-infected flocks. During this time, avian influenza viruses might be found in poultry products. LPAI viruses can be shed in asymptomatically infected or minimally affected flocks, but these viruses are unlikely to cause significant human disease.

  9. Interacting with the Human Insulin Receptor

    DEFF Research Database (Denmark)

    Kidmose, Rune Thomas; Andersen, Gregers Rom

    2016-01-01

    Insulin is an essential regulator of glucose homeostasis. In this issue of Structure, Croll et al. (2016) reports a significantly improved model of the Fab-complexed IR ectodomain refined against a dataset extending to 3.3 Å.......Insulin is an essential regulator of glucose homeostasis. In this issue of Structure, Croll et al. (2016) reports a significantly improved model of the Fab-complexed IR ectodomain refined against a dataset extending to 3.3 Å....

  10. An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

    Science.gov (United States)

    Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

    2015-04-01

    In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

  11. A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain.

    Science.gov (United States)

    Larsen, Inge; Hjulsager, Charlotte Kristiane; Holm, Anders; Olsen, John Elmerdahl; Nielsen, Søren Saxmose; Nielsen, Jens Peter

    2016-01-01

    Oral treatment with antimicrobials is widely used in pig production for the control of gastrointestinal infections. Lawsonia intracellularis (LI) causes enteritis in pigs older than six weeks of age and is commonly treated with antimicrobials. The objective of this study was to evaluate the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from 37 batches of nursery pigs were included in the study. The dosage regimens were randomly allocated to each batch and initiated at presence of assumed LI-related diarrhoea. In general, all OTC doses used for the treatment of LI infection resulted in reduced diarrhoea and LI shedding after treatment. Treatment with a low dose of 5mg/kg OTC per kg body weight, however, tended to cause more watery faeces and resulted in higher odds of pigs shedding LI above detection level when compared to medium and high doses (with odds ratios of 5.5 and 8.4, respectively). No association was found between the dose of OTC and the ADG. In conclusion, a dose of 5mg OTC per kg body weight was adequate for reducing the high-level LI shedding associated with enteropathy, but a dose of 10mg OTC per kg body weight was necessary to obtain a maximum reduction in LI shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Quantifying Children's Aggregate (Dietary and Residential) Exposure and Dose to Permethin: Application and Evaluation of EPA's Probabilistic SHED-Multimedia Model

    Science.gov (United States)

    Reliable, evaluated human exposure and dose models are important for understanding the health risks from chemicals. A case study focusing on permethrin was conducted because of this insecticide’s widespread use and potential health effects. SHEDS-Multimedia was applied to estimat...

  13. Effect of von Karman Vortex Shedding on Regular and Open-slit V-gutter Stabilized Turbulent Premixed Flames

    Science.gov (United States)

    2012-04-01

    Both flame lengths shrink and large scale disruptions occur downstream with vortex shedding carrying reaction zones. Flames in both flameholders...9) the flame structure changes dramatically for both regular and open-slit V-gutter. Both flame lengths shrink and large scale disruptions occur...reduces the flame length . However, qualitatively the open-slit V-gutter appears to be more sensitive than the regular V-gutter. Both flames remain

  14. Duration of growth depression and pathogen shedding in experimentally reproduced poult enteritis syndrome.

    Science.gov (United States)

    Jindal, Naresh; Patnayak, Devi P; Ziegler, Andre F; Lago, Alfonso; Goyal, Sagar M

    2009-12-01

    An experimental study was conducted to determine the duration of growth depression and virus shedding in turkey poults after oral inoculation with intestinal contents from birds affected with poult enteritis syndrome (PES). Poults at day 14 of age were divided into four groups (groups A, B, C, and D) of 40 poults each and inoculated orally with unfiltered supernatant, filtered supernatant, sediment suspended in phosphate-buffered saline (PBS), or PBS alone (control), respectively. The poults were observed daily for clinical signs, and their growth response, pathology, and pathogen shedding were examined at 10, 20, 30, 40, and 50 days postinoculation (DPI). Body weights of eight poults in each group were recorded at each of these intervals followed by euthanasia. Dullness, depression, and diarrhea were observed in birds inoculated with supernatant or sediment suspension. All three treatments significantly reduced body weight gain of poults compared with the control group; average weight loss was 14%. Gross pathologic changes consisted of pale distended intestines with watery contents and distended ceca with frothy and watery contents. Astrovirus and rotavirus were detected in the inoculum by reverse transcription (RT)-PCR, whereas Salmonella was identified on bacterial isolation. Both viruses were detected in treated poults by RT-PCR for up to 10 and 40 DPI, respectively. Of the three treatments, sediment suspension caused maximal decrease in weight gain as well as greatest pathologic lesions followed by unfiltered supernatant and filtered supernatant. These findings suggest a role for bacteria in increasing the severity of PES. Lower weight gain in treated poults (compared with controls) at 9 wk of age also indicates that PES-affected poults may not reach normal weight at marketing, leading to economic losses for the producer.

  15. Multi-frequency response of a cylinder subjected to vortex shedding and support motions

    Energy Technology Data Exchange (ETDEWEB)

    Vikestad, Kyrre

    1998-12-31

    This thesis deals with an experimental investigation of vortex induced vibrations of a circular cylinder. The purpose of the experiment was to identify the influence from a controlled disturbance of the cylinder motions on the response caused by vortex shedding. The cylinder investigated is 2 m long and the diameter is 10 cm. The cylinder is elastically mounted in an apparatus using springs, where the foundation of one of the springs can have a harmonic motion. The apparatus is placed on a carriage in a 25 m long towing tank. Towing velocities are varied between 0.140 m/s and 0.655 m/s corresponding to reduced velocity range from 2.8 to 13.2. The still water natural frequency is 0.497 Hz, and the natural frequency in air is 0.634 Hz. The cylinder is only able to oscillate in the cross-flow direction. The support motion frequency was varied between 0.26 Hz and 1.01 Hz, and the force motion amplitude was varied using 2, 4 and 6 cm support amplitudes. Three sets of experiments were carried out: (1) Still water oscillations due to harmonic support motion excitation, support amplitude and frequencies varied, (2) Towing tests with no support motion, the velocity is varied, (3) Combined excitation: Towing tests with support motion. All possible combinations of experiments (1) and (2) are carried out. The two first experiments provide reference values for the combined excitation experiments and for verification purposes. The results reveal the ability of the external disturbance to influence the vortex shedding process both regarding frequency and the resulting response amplitudes. Results for added mass, in-line drag and damping are also obtained. The work may be of use in deep water floating petroleum production. 81 refs., 73 figs., 6 tabs.

  16. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

    Science.gov (United States)

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  17. Zika virus shedding in human milk during lactation: an unlikely source of infection?

    Directory of Open Access Journals (Sweden)

    Marta G. Cavalcanti

    2017-04-01

    Full Text Available Zika virus (ZIKV transmission through non-mosquito-dependent routes has become increasingly important since reports of sexual transmission. Breastfeeding is a potential means of ZIKV transmission, but data on this remain limited. The cases of four mothers with laboratory-proven infections are reported. No disease evolved in three of the breastfed babies despite detectable maternal viremia and viruria, the presence of viral RNA shedding, and the isolation of infective particles in one milk sample. Fever and rash in one infant of a ZIKV-infected mother proved to be related to chikungunya virus infection. The results suggest that the presence of infective particles in breast milk may not be sufficient for the efficient perinatal transmission of ZIKV.

  18. Clausius’ Disgregation: A Conceptual Relic that Sheds Light on the Second Law

    Directory of Open Access Journals (Sweden)

    Emilio Marco Pellegrino

    2015-06-01

    Full Text Available The present work analyzes the cognitive process that led Clausius towards the translation of the Second Law of Thermodynamics into mathematical expressions. We show that Clausius’ original formal expression of the Second Law was achieved by making extensive use of the concept of disgregation, a quantity which has subsequently disappeared from the thermodynamic language. Our analysis demonstrates that disgregation stands as a crucial logical step of such process and sheds light on the comprehension of such fundamental relation. The introduction of entropy—which occurred three years after the first formalization of the Second Law—was aimed at making the Second Law exploitable in practical contexts. The reasons for the disappearance of disgregation, as well as of other “pre-modern” quantities, from the thermodynamics language are discussed.

  19. Transcriptome profiling of petal abscission zone and functional analysis of an Aux/IAA family gene RhIAA16 involved in petal shedding in rose

    Directory of Open Access Journals (Sweden)

    Yuerong Gao

    2016-09-01

    Full Text Available Roses are one of the most important cut flowers among ornamental plants. Rose flower longevity is largely dependent on the timing of petal shedding occurrence. To understand the molecular mechanism underlying petal abscission in rose, we performed transcriptome profiling of the petal abscission zone during petal shedding using Illumina technology. We identified a total of 2592 differentially transcribed genes (DTGs during rose petal shedding. Gene ontology term enrichment and pathway analysis revealed that major biochemical pathways the DTGs were involved in included ethylene biosynthesis, starch degradation, superpathway of cytosolic glycolysis, pyruvate dehydrogenase and TCA cycle, photorespiration and the lactose degradation III pathway. This suggests that alterations in carbon metabolism are an important part of rose petal abscission. Among these DTGs, approximately 150 genes putatively encoding transcription factors were identified in rose abscission zone. These included zinc finger, WRKY, ERF, and Aux/IAA gene families, suggesting that petal abscission involves complex transcriptional reprogramming. Approximately 108 DTGs were related to hormone pathways, of which auxin and ethylene related DTGs were the largest groups including 52 and 41 genes, respectively. These also included 12 DTGs related to gibberellin and 6 DTGs in jasmonic acid pathway. Surprisingly, no DTGs involved in the biosynthesis/signaling of abscisic acid, cytokinin, brassinosteroid, and salicylic acid pathways were detected. Moreover, among DTGs related to auxin, we identified an Aux/IAA gene RhIAA16 that was up-regulated in response to petal shedding. Down-regulation of RhIAA16 by virus-induced gene silencing in rose promoted petal abscission, suggesting that RhIAA16 plays an important role in rose petal abscission.

  20. Antemortem diagnosis of Mycobacterium bovis infection in free-ranging African lions (Panthera leo) and implications for transmission.

    Science.gov (United States)

    Miller, Michele; Buss, Peter; Hofmeyr, Jennifer; Olea-Popelka, Francisco; Parsons, Sven; van Helden, Paul

    2015-04-01

    Diagnosis of tuberculosis in wildlife often relies on postmortem samples because of logistical challenges and lack of field-friendly techniques for live animal testing. Confirmation of infection through detection of infectious organisms is essential for studying the pathogenesis and epidemiology of disease. We describe the application of a technique to obtain respiratory samples from free-ranging living lions to facilitate detection of viable Mycobacterium bovis under field conditions. We identified M. bovis by mycobacterial culture and PCR in tracheobronchial lavage samples from 8/134 (6.0%) lions tested in Kruger National Park, South Africa. This confirms the respiratory shedding of viable M. bovis in living lions. The implications of these results are that infected lions have the potential to transmit this disease and serve as maintenance hosts.

  1. HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration

    Science.gov (United States)

    Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

    2011-01-01

    Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

  2. Implications of the single supervisory mechanism on ECB's functions and on credit institutions' activity

    Directory of Open Access Journals (Sweden)

    Teodora Cristina BARBU

    2013-03-01

    Full Text Available The European Commission's proposal launched on September 12, 2012 for conferring the European Central Bank extended powers in the field of Euro zone banking supervision has become a hotly debated topic across EU member states. Until now, there is still strong resilience of the EU countries outside the single currency area.The prospects for its practical implementation raised, however, a series of questions related to its technical feasibility. Our paper intends to shed light on some issues concerning the implications of the single monitoring mechanism on the traditional functions of the ECB, on the coexistence between supranational supervision and the national one, and on various facets of the impact that the new architecture of European banking supervision will have on the business of credit institutions, in terms of performance indicators, efficiency, risk and competition.

  3. Sodium chlorate reduces presence of Escherichia coli in feces of lambs and ewes managed in shed-lambing systems

    Science.gov (United States)

    Our objective was to establish doses of orally-administered NaClO3 that reduced presence of generic Escherichia coli in intestines of ewes and neonatal lambs managed in a shed-lambing system. Neonatal lambs (n = 32; age = 7.1 ± 1.2 d; BW = 6.8 ± 1.0 kg) and yearling ewes (n = 44; BW = 74.8 ± 5.6 kg)...

  4. Cardiorespiratory effects of venous lipid micro embolization in an experimental model of mediastinal shed blood reinfusion

    Directory of Open Access Journals (Sweden)

    Dencker Magnus

    2009-09-01

    Full Text Available Abstract Background Retransfusion of the patient's own blood during surgery is used to reduce the need for allogenic blood transfusion. It has however been found that this blood contains lipid particles, which form emboli in different organs if the blood is retransfused on the arterial side. In this study, we tested whether retransfusion of blood containing lipid micro-particles on the venous side in a porcine model will give hemodynamic effects. Methods Seven adult pigs were used. A shed blood surrogate containing 400 ml diluted blood and 5 ml radioactive triolein was produced to generate a lipid embolic load. The shed blood surrogate was rapidly ( Results A more than 30-fold increase in pulmonary vascular resistance was observed, with subsequent increase in pulmonary artery pressure, and decrease in cardiac output and arterial pressure. This response was transient, but was followed by a smaller, persistent increase in pulmonary vascular resistance. Only a small portion of the infused triolein passed the lungs, and only a small fraction could be recirculated by increasing cardiac output and pulmonary pressure. Conclusion Infusion of blood containing lipid micro-emboli on the venous side leads to acute, severe hemodynamic responses that can be life threatening. Lipid particles will be trapped in the lungs, leading to persistent effects on the pulmonary vascular resistance.

  5. Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15

    Directory of Open Access Journals (Sweden)

    Jinlan Wang

    2016-05-01

    Full Text Available Toll-like receptors (TLRs play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein–protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops and αC-helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation.

  6. Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge.

    Science.gov (United States)

    Morello, Christopher S; Kraynyak, Kimberly A; Levinson, Michael S; Chen, Zhijiang; Lee, Kuo-Fen; Spector, Deborah H

    2012-10-12

    Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Spectroscopic and thermal characterization of alternative model biomembranes from shed skins of Bothrops jararaca and Spilotis pullatus

    Directory of Open Access Journals (Sweden)

    André Rolim Baby

    2009-09-01

    Full Text Available Recently, there has been an interest in the use of shed snake skin as alternative model biomembrane for human stratum corneum. This research work presented as objective the qualitative characterization of alternative model biomembranes from Bothrops jararaca and Spilotis pullatus by FT-Raman, PAS-FTIR and DSC. The employed biophysical techniques permitted the characterization of the biomembranes from shed snake skin of B. jararaca and S. pullatus by the identification of vibrational frequencies and endothermic transitions that are similar to those of the human stratum corneum.Existe atualmente interesse no uso da muda de pele de cobra como modelos alternativos de biomembranas da pele humana. O presente trabalho apresentou como objetivo a caracterização qualitativa de modelos alternativos de biomembranas provenientes de mudas de pele de cobra da Bothrops jararaca e Spilotis pullatus por espectroscopia Raman (FT-Raman, espectroscopia fotoacústica no infravermelho (PAS-FTIR e calorimetria exploratória diferencial (DSC. As técnicas biofísicas FT-Raman, PAS-FTIR e DSC permitiram caracterizar qualitativamente os modelos alternativos de biomembranas provenientes das mudas de pele de cobra da B. jararaca e S. pullatus e identificar freqüências vibracionais e transições endotérmicas similares ao estrato córneo humano.

  8. Interaction between thermal environments and hormones affecting skin-shedding frequency in the tokay (Gekko gecko) (Gekkonidae, Lacertilia).

    Science.gov (United States)

    Chiu, K W; Sham, J S; Maderson, P F; Zucker, A H

    1986-01-01

    Effects of thyroidectomy and/or hypophysectomy on the skin-shedding frequency (SF) in the tokay Gekko gecko and of thyroid hormones on the oxygen consumption (OCR) at various temperature regimes have been determined. Surgery invariably protracted the cycle length, thus decreasing SF; the extent of these changes was temperature dependent, the higher the temperature, the less the difference. Effects of hypophysectomy on cycle length were expressed in two phases; an extended first post-operative cycle was followed by a further extended second post-operative cycle, with cycle length forming a plateau thereafter. With time, the operated tokays would die without shedding during a greatly protracted cycle. OCRs in the tokay were temperature dependent, but between 28 and 34 degrees C, no significant difference could be seen. Effects of thyroid hormones on OCR were also temperature dependent. Furthermore, tokays having higher OCR were shown to have shorter cycles and vice versa. Results showed that whatever effect hormone(s) have on SF is indirect through general metabolic changes. SF is merely a reflection of the general metabolic status of the animal. It is proposed that the role of hormone(s), those of the thyroid in particular, is to act as "fine-tuning" devices in the regulation of metabolism and, as such, of the viability of the animal.

  9. Shedding Light on Students' Technology Preferences: Implications for Academic Development

    Science.gov (United States)

    Mirriahi, Negin; Alonzo, Dennis

    2015-01-01

    This study built on previous research in 2010 to determine changes to students' current use of and expectations for future integration of technologies in their learning experience. The findings reveal a continued trend of conservative technology use amongst students but with a growing demand for more integration of technologies for assessment and…

  10. Cryogenic transmission electron microscopy nanostructural study of shed microparticles.

    Directory of Open Access Journals (Sweden)

    Liron Issman

    Full Text Available Microparticles (MPs are sub-micron membrane vesicles (100-1000 nm shed from normal and pathologic cells due to stimulation or apoptosis. MPs can be found in the peripheral blood circulation of healthy individuals, whereas elevated concentrations are found in pregnancy and in a variety of diseases. Also, MPs participate in physiological processes, e.g., coagulation, inflammation, and angiogenesis. Since their clinical properties are important, we have developed a new methodology based on nano-imaging that provides significant new data on MPs nanostructure, their composition and function. We are among the first to characterize by direct-imaging cryogenic transmitting electron microscopy (cryo-TEM the near-to-native nanostructure of MP systems isolated from different cell types and stimulation procedures. We found that there are no major differences between the MP systems we have studied, as most particles were spherical, with diameters from 200 to 400 nm. However, each MP population is very heterogeneous, showing diverse morphologies. We investigated by cryo-TEM the effects of standard techniques used to isolate and store MPs, and found that either high-g centrifugation of MPs for isolation purposes, or slow freezing to -80 °C for storage introduce morphological artifacts, which can influence MP nanostructure, and thus affect the efficiency of these particles as future diagnostic tools.

  11. Behavioural repertoire of free-range laying hens indoors and outdoors, and in relation to distance from the shed.

    Science.gov (United States)

    Thuy Diep, A; Larsen, H; Rault, J-L

    2018-04-01

    Access to an outdoor area is believed to allow free-range hens to express a greater behavioural repertoire. However, very little research has been done in this area. We hypothesised that the type and frequency of behaviours would differ between areas that vary in their characteristics and distance from the shed. This preliminary study investigated the behaviour of free-range laying hens in indoor and outdoor areas on one commercial free-range farm, through video recordings and scan sampling of focal hens, with the aim of determining their behavioural repertoire and time budget. While ranging, hens spent most of their time foraging. Indoors, hens preened and rested. Behaviour in the wintergarden showed similarities to both the indoor and outdoor areas, with preening, resting and foraging behaviours. Differences were not in the main behavioural repertoire, but rather in terms of time budget, with access to the range and wintergarden encouraging exploration. There was no difference in the types of behaviours that hens performed in the outdoor range compared with inside the shed, but access to a wintergarden and the outdoor range were favoured by the hens for foraging. © 2018 Australian Veterinary Association.

  12. Combustion heat release effects on asymmetric vortex shedding from bluff bodies

    Science.gov (United States)

    Cross, Caleb Nathaniel

    2011-07-01

    This thesis describes an investigation of oscillatory combustion processes due to vortex shedding from bluff body flame holders. The primary objective of this study was to elucidate the influence of combustion process heat release upon the Benard-von Karman (BVK) instability in reacting bluff body wakes. For this purpose, spatial and temporal heat release distributions in bluff body-stabilized combustion of liquid Jet-A fuel with high-temperature, vitiated air were characterized over a wide range of operating conditions. Two methods of fuel injection were investigated. In the first method, referred to as close-coupled fuel injection, the fuel was supplied via discrete liquid jets injected perpendicular to the cross-flowing air stream just upstream of the bluff body trailing edge, thereby limiting fuel and air mixing prior to burning. The fuel was introduced well upstream (˜0.5 m) of the bluff body in the second fuel injection mode, resulting in a well-evaporated and mixed reactants stream. The resulting BVK heat release dynamics were compared between these fuel injection modes in order to investigate their dependence upon the spatial distributions of fuel-air ratio and heat release in the reacting wake. When close-coupled fuel injection was used, the BVK heat release dynamics increased in amplitude with increasing global equivalence ratio, reaching a maximum just before globally rich blow out of the combustion process occurred. This was due to a decrease in fuel entrainment into the near-wake as the fuel spray penetrated further into the cross-flow, which reduced the local heat release and equivalence ratio (indicated by CH* and C2*/CH* chemiluminescence, respectively). As a result, the density gradient across the near-wake reaction zone decreased, resulting in less damping of vorticity due to dilatation. In addition, unburned reactants were entrained into the recirculation zone due to the injection of discrete liquid fuel jets in close proximity to the wake. This

  13. Hair shedding score may affect body temperature more than hair coat color during heat stress in weaned beef heifers.

    Science.gov (United States)

    The objective of this study was to evaluate the effect of hair shedding score and hair coat color on the vaginal temperature (VT) of calves during heat stress. Weaned Bos taurus beef heifers (n = 32; BW = 282 ± 6.4 kg) were assigned to a hair coat color class (BLACK; RED; or LIGHT, where LIGHT = yel...

  14. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    Science.gov (United States)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

  15. Shedding and serologic responses following primary and secondary inoculation of house sparrows (Passer domesticus) and European starlings (Sturnus vulgaris) with low-pathogenicity avian influenza virus.

    Science.gov (United States)

    Nemeth, Nicole M; Thomas, Nicholas O; Orahood, Darcy S; Anderson, Theodore D; Oesterle, Paul T

    2010-10-01

    Waterfowl and shorebirds are well-recognized natural reservoirs of low-pathogenicity avian influenza viruses (LPAIV); however, little is known about the role of passerines in avian influenza virus ecology. Passerines are abundant, widespread, and commonly come into contact with free-ranging birds as well as captive game birds and poultry. We inoculated and subsequently challenged house sparrows (Passer domesticus) and European starlings (Sturnus vulgaris) with wild-bird origin LPAIV H3N8 to evaluate their potential role in transmission. Oropharyngeal shedding was short lived, and was detected in more starlings (97.2%) than sparrows (47.2%; n=36 of each). Cloacal shedding was rare in both species (8.3%; n=36 of each) and no cage-mate transmission occurred. Infectious LPAIV was cultured from oropharyngeal and cloacal swabs and gastrointestinal and respiratory tissues from both species. Seroconversion was detected as early as 3 days post inoculation (d.p.i.) (16.7% of sparrows and 0% of starlings; n=6 each); 50% of these individuals seroconverted by 5 d.p.i., and nearly all birds (97%; n=35) seroconverted by 28 d.p.i. In general, pre-existing homologous immunity led to reduced shedding and increased antibody levels within 7 days of challenge. Limited shedding and lack of cage-mate transmission suggest that passerines are not significant reservoirs of LPAIV, although species differences apparently exist. Passerines readily and consistently seroconverted to LPAIV, and therefore inclusion of passerines in epidemiological studies of influenza outbreaks in wildlife and domestic animals may provide further insight into the potential involvement of passerines in avian influenza virus transmission ecology.

  16. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

    Science.gov (United States)

    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

  17. Other Perspectives for Developing Exposure Estimates: “SHEDS-Lite: Rapid Scenario-Based ExposurePredictions for Chemicals with Near-Field and Dietary Pathways”

    Science.gov (United States)

    Creative advances in exposure science are needed to support efficient and effective evaluation and management of chemical risks, particularly for chemicals in consumer products. This presentation will describe the development of EPA’s screening-level, probabilistic SHEDS-Li...

  18. Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

    Science.gov (United States)

    Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

    2017-03-08

    TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

  19. SHEDS-Multimedia Model Version 3 (a) Technical Manual; (b) User Guide; and (c) Executable File to Launch SAS Program and Install Model

    Science.gov (United States)

    Reliable models for assessing human exposures are important for understanding health risks from chemicals. The Stochastic Human Exposure and Dose Simulation model for multimedia, multi-route/pathway chemicals (SHEDS-Multimedia), developed by EPA’s Office of Research and Developm...

  20. Effect of essential oil compound on shedding and colonization of Salmonella enterica serovar Heidelberg in broilers.

    Science.gov (United States)

    Alali, W Q; Hofacre, C L; Mathis, G F; Faltys, G

    2013-03-01

    The objectives of this study were to determine the effect of an essential oil blend (EO; carvacrol, thymol, eucalyptol, lemon) administered in drinking water on the performance, mortality, water consumption, pH of crop and ceca, and Salmonella enterica serovar Heidelberg fecal shedding and colonization in broiler birds following Salmonella Heidelberg challenge and feed withdrawal. Chicks were randomly assigned to water treatments containing 0.05, 0.025, or 0.0125% EO or untreated controls. Treatments were administered in drinking water on 0 to 7 and 35 to 42 d. One-half of the chicks were challenged with Salmonella Heidelberg and placed in pens with unchallenged chicks on d 1. Performance, mortality, water consumption, and pH were determined during the 42-d study. Prevalence of Salmonella Heidelberg was determined on drag swabs (0, 14, and 42 d) and in the ceca and crops (42 d). The 0.05% EO administered in drinking water significantly (P water significantly lowered the feed conversion ratio and increased weight gain compared with controls, but did not significantly reduce Salmonella Heidelberg colonization in the crops. The EO in drinking water did not significantly reduce Salmonella Heidelberg colonization in ceca or fecal shedding in broilers. The EO used in the study may control Salmonella Heidelberg contamination in crops of broilers when administered in drinking water and therefore may reduce the potential for cross-contamination of the carcass when the birds are processed.

  1. Optimal Load Shedding and Generation Rescheduling for Overload Suppression in Large Power Systems.

    Science.gov (United States)

    Moon, Young-Hyun

    Ever-increasing size, complexity and operation costs in modern power systems have stimulated the intensive study of an optimal Load Shedding and Generator Rescheduling (LSGR) strategy in the sense of a secure and economic system operation. The conventional approach to LSGR has been based on the application of LP (Linear Programming) with the use of an approximately linearized model, and the LP algorithm is currently considered to be the most powerful tool for solving the LSGR problem. However, all of the LP algorithms presented in the literature essentially lead to the following disadvantages: (i) piecewise linearization involved in the LP algorithms requires the introduction of a number of new inequalities and slack variables, which creates significant burden to the computing facilities, and (ii) objective functions are not formulated in terms of the state variables of the adopted models, resulting in considerable numerical inefficiency in the process of computing the optimal solution. A new approach is presented, based on the development of a new linearized model and on the application of QP (Quadratic Programming). The changes in line flows as a result of changes to bus injection power are taken into account in the proposed model by the introduction of sensitivity coefficients, which avoids the mentioned second disadvantages. A precise method to calculate these sensitivity coefficients is given. A comprehensive review of the theory of optimization is included, in which results of the development of QP algorithms for LSGR as based on Wolfe's method and Kuhn -Tucker theory are evaluated in detail. The validity of the proposed model and QP algorithms has been verified and tested on practical power systems, showing the significant reduction of both computation time and memory requirements as well as the expected lower generation costs of the optimal solution as compared with those obtained from computing the optimal solution with LP. Finally, it is noted that an

  2. Model Tests of Under Frequency Load Shedding (UFLS for Connected Systems of Continental Europe

    Directory of Open Access Journals (Sweden)

    Marek Głaz

    2016-09-01

    Full Text Available The task force set up by working group System Protection and Dynamics within ENTSO-E model tests of Under Frequency Load Shedding (UFLS for connected systems of continental Europe were carried out. Over 360 simulation scenarios were performed including 16 strategies UFLS, 2 variants of load, 6 types of contingency, with and without considering the impact of dispersed generation. On the basis of calculation results conditions for improving the effectiveness of the UFLS were specified,, including recommended changes of UFLS settings, necessary to achieve this aim. The following report contains a summary description of the test method together with the presentation of selected results of summary calculations and conclusions of the study.

  3. Ebola Virus Shedding and Transmission: Review of Current Evidence.

    Science.gov (United States)

    Vetter, Pauline; Fischer, William A; Schibler, Manuel; Jacobs, Michael; Bausch, Daniel G; Kaiser, Laurent

    2016-10-15

     The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.  We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.  Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Correlates of HIV-1 genital shedding in Tanzanian women.

    Directory of Open Access Journals (Sweden)

    Clare Tanton

    2011-03-01

    Full Text Available Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania.Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load.Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load.RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

  5. Development of a wide range vortex shedding flowmeter for high temperature helium gas

    Energy Technology Data Exchange (ETDEWEB)

    Baker, S.P.; Ennis, R.M. Jr.; Herndon, P.G.

    1981-07-01

    A flowmeter was required to measure recirculating helium gas flow over a wide range of conditions in a gas-cooled fast reactor (GCFR) core flow simulator, the ORNL Core Flow Test Loop (CFTL). The flow measurement requirements of the CFTL exceeded the proven performance of any single conventional flowmeter. Therefore, a special purpose vortex shedding flowmeter (VSFM) was developed. A single flowmeter capable of meeting all the CFTL requirements would provide significant economic and performance advantages in the operation of the loop. The development, conceptual design, and final design of a modified VSFM are described. The results of extensive flow calibration of the flowmeter at the Colorado Engineering Experiment Station (CEES) are presented. The report closes with recommendations for application of the VSFM to the CFTL and for future development work.

  6. Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

    Science.gov (United States)

    Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

    2014-01-01

    Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

  7. Characterization of stormwater at selected South Carolina Department of Transportation maintenance yards and section shed facilities in Ballentine, Conway, and North Charleston, South Carolina, 2010-12

    Science.gov (United States)

    Journey, Celeste A.; Conlon, Kevin J.

    2014-01-01

    Increased impervious surfaces (driveways, parking lots, and buildings) and human activities (residential, industrial, and commercial) have been linked to substantial changes in both the quality and quantity of stormwater on a watershed scale (Brabec and others, 2002; Pitt and Maestre, 2005). Small-scale storage and equipment repair facilities increase impervious surfaces that prevent infiltration of stormwater, and these facilities accommodate activities that can introduce trace metals, organic compounds, and other contaminants to the facility’s grounds. Thus, these small facilities may contribute pollutants to the environment during storm events (U.S. Environmental Protection Agency, 1992). The South Carolina Department of Transportation (SCDOT) operates section shed and maintenance yard facilities throughout the State. Prior to this investigation, the SCDOT had no data to define the quality of stormwater leaving these facilities. To provide these data, the U.S. Geological Survey (USGS), in cooperation with the SCDOT, conducted an investigation to identify and quantify constituents that are transported in stormwater from two maintenance yards and a section shed in three different areas of South Carolina. The two maintenance yards, in North Charleston and Conway, S.C., were selected because they represent facilities where equipment and road maintenance materials are stored and complete equipment repair operations are conducted. The section shed, in Ballentine, S.C., was selected because it is a facility that stores equipment and road maintenance material. Characterization of the constituents that were transported in stormwater from these representative SCDOT maintenance facilities may be used by the SCDOT in the development of stormwater management plans for similar section shed and maintenance yard facilities throughout the State to improve stormwater quality.

  8. Mapping human interaction with the Bering Sea ecosystem: Comparing seasonal use areas, lifetime use areas, and "calorie-sheds"

    Science.gov (United States)

    Huntington, Henry P.; Ortiz, Ivonne; Noongwook, George; Fidel, Maryann; Childers, Dorothy; Morse, Muriel; Beaty, Julia; Alessa, Lilian; Kliskey, Andrew

    2013-10-01

    Alaska Native coastal communities interact with the marine environment in many ways, especially through the harvest of fish, marine mammals, and seabirds. The spatial characteristics of this interaction are often depicted in terms of subsistence use areas: the places where harvests and associated travel occur. Another way to consider the interaction is to examine the areas where harvested species range during their lifecycle or annual migratory path. In this paper, we compare seasonal subsistence use areas, lifetime subsistence use areas, and "calorie-sheds," or the area over which harvested species range. Each perspective offers useful information concerning not only the nature of human-environment interactions but also the scope for potential conflict with other human activity and the means by which such conflicts could be reduced, avoided, or otherwise addressed. Seasonal subsistence use areas can be used to manage short-term activities, such as seasonal vessel traffic during community re-supply. Lifetime subsistence use areas indicate the area required to allow hunters and fishers the flexibility to adjust to interannual variability and perhaps to adapt to a changing environment. Calorie-sheds indicate the areas about which a community may be concerned due to potential impacts on the species they harvest.

  9. Classification of temporal profiles of F4+ E. coli shedding and faecal dry matter in experimental post-weaning diarrhoea of pigs

    NARCIS (Netherlands)

    Geenen, P.L.; Meulen, van der J.; Bouma, A.; Engel, B.; Heesterbeek, J.A.P.; Jong, de M.C.M.

    2007-01-01

    Enterotoxigenic F4+ Escherichia coli can colonize the intestine of pigs and cause diarrhoea. Our primary goal was to find a discriminant rule to discriminate between F4+ E. coli shedding profiles as this may reflect differences in the infectiousness of pigs. Our secondary goal was to find a

  10. Classification of temporal profiles of F4+ E. coli shedding and faecal dry matter in experimental post-weaning diarrhoea of pigs

    NARCIS (Netherlands)

    Geenen, P.L.; Meulen, J. van der; Bouma, A.; Engel, B.; Heesterbeek, J.A.P.; Jong, M.C.M. de

    2006-01-01

    Enterotoxigenic F4+ Escherichia coli can colonize the intestine of pigs and cause diarrhoea. Our primary goal was to find a discriminant rule to discriminate between F4+ E. coli shedding profiles as this may reflect differences in the infectiousness of pigs. Our secondary goal was to find a

  11. Zebrafish models flex their muscles to shed light on muscular dystrophies.

    Science.gov (United States)

    Berger, Joachim; Currie, Peter D

    2012-11-01

    Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

  12. Cytotoxicity of accelerated white MTA and Malaysian white Portland cement on stem cells from human exfoliated deciduous teeth (SHED): An in vitro study.

    Science.gov (United States)

    Ong, Ren Ming; Luddin, Norhayati; Ahmed, Hany Mohamed Aly; Omar, Nor Shamsuria

    2012-12-01

    The aim of this study was to compare the cytotoxicity of accelerated-set white MTA (AWMTA) and accelerated-set Malaysian white PC (AMWPC) on stem cells from human exfoliated deciduous teeth (SHED). The test materials were introduced into paraffin wax moulds after mixing with calcium chloride dihydrate and sterile distilled water. Subsequently, the set cement specimens were sterilized, incubated in a prepared Dulbecco's modified Eagle medium (DMEM) for seven days. The biomarker CD166 was used for characterization of SHED using flow cytometry. The material extracts were diluted at five different concentrations and incubated for 72h with SHED. The cell viability was evaluated using Dimethylthiazol diphenyltetrazolium bromide (MTT) assay, and the data was analysed using Mann-Whitney test (P<0.05). The results showed that AWMTA revealed significantly greater cell viability at 25 and 12.5mg/ml concentrations (P<0.05). Concomitantly, AMWPC exhibited greater cell viability at concentrations <12.5mg/ml and the results were significant at 1.563mg/ml (P<0.05). Both materials demonstrated moderate cytotoxicity at 25mg/ml and slight cytotoxicity at 6.25 and 3.125mg/ml. At 1.563mg/ml, no cytotoxic activity was merely observed with AMWPC. In conclusion, AMWPC exhibited favourable and comparable cell viability to that of AWMTA, and has the potential to be used as an alternative and less costly material in dental applications. Copyright © 2012. Published by Elsevier B.V.

  13. Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway

    International Nuclear Information System (INIS)

    Yu, Shengjin; Lv, Huiming; Zhang, He; Jiang, Yu; Hong, Yu; Xia, Rongjun; Zhang, Qifang; Ju, Weiwei; Jiang, Lili; Ou, Geng; Zhang, Jinhui; Wang, Shujing; Zhang, Jianing

    2017-01-01

    Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERK) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis. - Highlights: • SDC-1 anchors VEGF-C via its HS chains. • Secreted HPA-1 from hepatocarcinoma cell cleaves HS chains of SDC-1. • The shedding of SDC-1 HS chains releases VEGF-C from SDC-1/VEGF-C complex. • LMWH inhibits VEGF-C secretion through stabilizing SDC-1/VEGF-C complex. • VEGF-C secretion from hepatocarcinoma cell facilitates LEC growth via ERK signaling.

  14. The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures

    Science.gov (United States)

    Muñoz, Manuel; Ariza, Daniel; Campos, Arturo; Martín-Montañez, Elisa; Pavía, José

    2013-01-01

    Background Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20–50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. Materials and methods Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT®, Wellspect HealthCare and ConstaVac CBC II®, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. Results Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € −51.9 to € 49.9/patient for ConstaVac CBCII). Discussion Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin cost-saving, its efficacy could be increased by

  15. Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 4. Infective doses and pathogen carriage.

    Science.gov (United States)

    Todd, Ewen C D; Greig, Judy D; Bartleson, Charles A; Michaels, Barry S

    2008-11-01

    In this article, the fourth in a series reviewing the role of food workers in foodborne outbreaks, background information on the presence of enteric pathogens in the community, the numbers of organisms required to initiate an infection, and the length of carriage are presented. Although workers have been implicated in outbreaks, they were not always aware of their infections, either because they were in the prodromic phase before symptoms began or because they were asymptomatic carriers. Pathogens of fecal, nose or throat, and skin origin are most likely to be transmitted by the hands, highlighting the need for effective hand hygiene and other barriers to pathogen contamination, such as no bare hand contact with ready-to-eat food. The pathogens most likely to be transmitted by food workers are norovirus, hepatitis A virus, Salmonella, Shigella, and Staphylococcus aureus. However, other pathogens have been implicated in worker-associated outbreaks or have the potential to be implicated. In this study, the likelihood of pathogen involvement in foodborne outbreaks where infected workers have been implicated was examined, based on infectious dose, carriage rate in the community, duration of illness, and length of pathogen excretion. Infectious dose estimates are based on volunteer studies (mostly early experiments) or data from outbreaks. Although there is considerable uncertainty associated with these data, some pathogens appear to be able to infect at doses as low as 1 to 100 units, including viruses, parasites, and some bacteria. Lengthy postsymptomatic shedding periods and excretion by asymptomatic individuals of many enteric pathogens is an important issue for the hygienic management of food workers.

  16. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the

  17. Analogies between oscillation and rotation of bodies induced or influenced by vortex shedding

    Science.gov (United States)

    Lugt, H. J.

    Vortex-induced or vortex-influenced rotation and oscillation of bodies in a parallel flow are discussed. A steady flow occurs if the body axis is parallel to the flow or if the axis of rotation is perpendicular to the flow. Flows around an oscillating body are quasi-steady only if the Strougal number is much smaller than unity. The connection between rotation and oscillation is demonstrated in terms of the autorotation of a Lanchester propeller, and conditions for stable autorotation are defined. The Riabouchinsky curve is shown to be typical of forces and torques on bodies with vortical wakes, including situations with fixed body axes perpendicular to the flow. A differential equation is formulated for rotational and oscillating bodies that shed vortices by extending the pendulum equation to include vortical effects expressed as a fifth-order polynomial.

  18. HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand.

    Science.gov (United States)

    Forhan, S E; Dunne, E F; Sternberg, M R; Whitehead, S J; Leelawiwat, W; Thepamnuay, S; Chen, C; Evans-Strickfaden, Tt; McNicholl, J M; Markowitz, L E

    2012-08-01

    We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P genital sampling, and inclusion of genital sites other than the cervix.

  19. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. Methods: WLWH between 18...

  20. Autonomous vehicles:challenges, opportunities, and future implications for transportation policies

    Institute of Scientific and Technical Information of China (English)

    Saeed Asadi Bagloee; Madjid Tavana; Mohsen Asadi; Tracey Oliver

    2016-01-01

    This study investigates the challenges and opportunities pertaining to transportation policies that may arise as a result of emerging autonomous vehicle (AV) technologies. AV technologies can decrease the trans-portation cost and increase accessibility to low-income households and persons with mobility issues. This emerg-ing technology also has far-reaching applications and implications beyond all current expectations. This paper provides a comprehensive review of the relevant literature and explores a broad spectrum of issues from safety to machine ethics. An indispensable part of a prospective AV development is communication over cars and infrastructure (connected vehicles). A major knowledge gap exists in AV technology with respect to routing behaviors. Connected-vehicle technology provides a great opportunity to imple-ment an efficient and intelligent routing system. To this end, we propose a conceptual navigation model based on a fleet of AVs that are centrally dispatched over a network seeking system optimization. This study contributes to the literature on two fronts: (i) it attempts to shed light on future opportunities as well as possible hurdles associated with AV technology;and (ii) it conceptualizes a navigation model for the AV which leads to highly efficient traffic circulations.

  1. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal.

    Science.gov (United States)

    Scavone, J L; Sterling, R C; Van Bockstaele, E J

    2013-09-17

    Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive physical and emotional symptoms. High rates of relapse and limited treatment success rates for opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving abstinence may be further complicated by poly-drug use and co-morbid mental disorders. Research over the past decade has shed light on the influence of endocannabinoids (ECs) on the opioid system. Evidence from both animal and clinical studies point toward an interaction between these two systems, and suggest that targeting the EC system may provide novel interventions for managing opiate dependence and withdrawal. This review will summarize the literature surrounding the molecular effects of cannabinoids and opioids on the locus coeruleus-norepinephrine system, a key circuit implicated in the negative sequelae of opiate addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to abstain from opiates in the clinical setting will also be presented. In summary, the present review details how cannabinoid-opioid interactions may inform novel interventions in the management of opiate dependence and withdrawal. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Circulation of Coxiella burnetii in a Naturally Infected Flock of Dairy Sheep: Shedding Dynamics, Environmental Contamination, and Genotype Diversity

    OpenAIRE

    Joulié, A.; Laroucau, K.; Bailly, X.; Prigent, M.; Gasqui, P.; Lepetitcolin, E.; Blanchard, B.; Rousset, E.; Sidi-Boumedine, K.; Jourdain, E.

    2015-01-01

    Q fever is a worldwide zoonosis caused by Coxiella burnetii. Domestic ruminants are considered to be the main reservoir. Sheep, in particular, may frequently cause outbreaks in humans. Because within-flock circulation data are essential to implementing optimal management strategies, we performed a follow-up study of a naturally infected flock of dairy sheep. We aimed to (i) describe C. burnetii shedding dynamics by sampling vaginal mucus, feces, and milk, (ii) assess circulating strain divers...

  3. Decentralized Coordination of Load Shedding and Plant Protection Considering High Share of RESs

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Silva, Filipe Miguel Faria da; Bak, Claus Leth

    2016-01-01

    variable using voltage drop data coordinated with plant protection scheme. A frequency anti stalling scheme is developed to interrupt more load feeders in case of frequency stall between consecutive set points. This time-based approach adjusts the time delay of the relay stages to disconnect the feeders...... with more voltage drop first, in order to bring the frequency back to the permissible range before the tolerable time period of plant protection relays is over. The load curtailment is stopped to avoid over LS, if the proposed algorithm recognizes that the frequency reaches the safe region in time based......This paper estimates the average Rate of Change of Frequency (ROCOF) following islanding and/or cascading event/s using inflection points of frequency profile. Moreover, a frequency collapse barrier scheme is set up by tuning the frequency set points of Load Shedding (LS) relays as a dynamic...

  4. CD62L (L-selectin) shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.

    Science.gov (United States)

    Erdoes, Gabor; Balmer, Maria L; Slack, Emma; Kocsis, Istvan; Lehmann, Lutz E; Eberle, Balthasar; Stüber, Frank; Book, Malte

    2013-01-01

    To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass. Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation. 25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p ≤ 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401). Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF

  5. CD62L (L-selectin shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.

    Directory of Open Access Journals (Sweden)

    Gabor Erdoes

    Full Text Available To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA and tumor necrosis factor alpha (TNF--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA-DR, and plasma interleukin (IL-8, soluble (sCD62L, soluble (sToll-like receptor (TLR-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively. In contrast, granulocytes (p = 0.01, but not monocytes (p = 0.057 displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001 and sTLR (p = 0.004, and decreases in monocyte HLA-DR (p<0.001, plasma sCD62L (p ≤ 0.001. In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401.Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF

  6. Implicative Algebras

    African Journals Online (AJOL)

    Tadesse

    In this paper we introduce the concept of implicative algebras which is an equivalent definition of lattice implication algebra of Xu (1993) and further we prove that it is a regular Autometrized. Algebra. Further we remark that the binary operation → on lattice implicative algebra can never be associative. Key words: Implicative ...

  7. The tryptic cleavage product of the mature form of the bovine desmoglein 1 ectodomain is one of the antigen moieties immunoprecipitated by all sera from symptomatic patients affected by a new variant of endemic pemphigus.

    Science.gov (United States)

    Abréu-Vélez, Ana María; Javier Patiño, Pablo; Montoya, Fernando; Bollag, Wendy B

    2003-01-01

    Multiple antigens are recognized by sera from patients with pemphigus foliaceus (PF). Several have been identified including keratin 59, desmocollins, envoplakin, periplakin, and desmogleins 1 and 3 (Dsg1 and Dsg3). In addition, an 80 kDa antigen was identified as the N-terminal fragment of Dsg1 using as antigen source an insoluble epidermal cell envelope preparation. However, still unsolved was the identity of the most important antigenic moiety, a 45 kDa tryptic fragment which is recognized by all sera from patients with fogo selvagem, pemphigus foliaceus, by half of pemphigus vulgaris sera and by a new variant of endemic pemphigus in E1 Bagre, Colombia that resembles Senear-Usher syndrome. Here, we report the identification of the 45 kDa conformational epitope of a soluble tryptic cleavage product from viable bovine epidermis. To elucidate the nature of this peptide, viable bovine epidermis was trypsin-digested, and glycosylated peptides were partially purified on a concanavalin A (Con-A) affinity column. This column fraction was then used as an antigen source for further immunoaffinity purification. A PF patient's serum covalently coupled to a Staphylococcus aureus protein A column was incubated with the Con-A eluted products and the immuno-isolated antigen was separated by SDS-PAGE, transferred to a membrane, and visualized with Coomassie blue, silver and amido black stains. The 45 kD band was subjected to amino acid sequence analysis revealing the sequence, EXIKFAAAXREGED, which matched the mature form of the extracellular domain of bovine Dsg1. This study confirms the biological importance of the ectodomain of Dsg1 as well as the relevance of conformational epitopes in various types of pemphigus.

  8. Vaccination against porcine parvovirus protects against disease, but does not prevent infection and virus shedding after challenge infection with a heterologous virus strain.

    Science.gov (United States)

    Jóźwik, A; Manteufel, J; Selbitz, H-J; Truyen, U

    2009-10-01

    The demonstration of field isolates of porcine parvovirus (PPV) that differ genetically and antigenically from vaccine strains of PPV raises the question of whether the broadly used inactivated vaccines can still protect sows against the novel viruses. Ten specific-pathogen-free primiparous sows were assigned to three groups and were vaccinated with one of two vaccines based on the old vaccine strains, or served as non-vaccinated controls. After insemination, all sows were challenged with the prototype genotype 2 virus, PPV-27a, on gestation day 41; fetuses were delivered on gestation day 90 and examined for virus infection. The fetuses of the vaccinated sows were protected against disease, but both the vaccinated and the non-vaccinated sows showed a marked increase in antibody titres after challenge infection, indicating replication of the challenge virus. All sows (vaccinated and non-vaccinated) shed the challenge virus for at least 10 days after infection, with no difference in the pattern or duration of virus shedding.

  9. Effect of severe weather events on the shedding of Shiga toxigenic Escherichia coli in slaughter cattle and phenotype of serogroup O157 isolates.

    Science.gov (United States)

    Stanford, Kim; Reuter, Tim; Bach, Susan J; Chui, Linda; Ma, Angela; Conrad, Cheyenne C; Tostes, Renata; McAllister, Tim A

    2017-09-01

    High-event periods (HEPs) occur sporadically when beef carcasses and meat have episodes of acute contamination with Shiga toxin-producing Escherichia coli (STEC). In this study, severe weather events were investigated as catalysts for HEPs based on PCR and isolate prevalence of seven E. coli serogroups in slaughter cattle feces. Winter ambient temperatures with daily means 10.5oC warmer or 12.3°C colder than seasonal norms (-10.4°C) most altered STEC shedding. Fecal samples yielded increased proportions (P  10 min and one also had strong biofilm-forming potential. However, this isolate lacked eae and stx genes. Severe weather can influence STEC shedding, particularly of O157, and could possibly trigger HEPs. However, our data suggest that it is unlikely for isolates to carry virulence genes and possess phenotypes capable of evading post-harvest microbiological interventions. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Peptidomics for Studying Limited Proteolysis.

    Science.gov (United States)

    Tsuchiya, Takashi; Osaki, Tsukasa; Minamino, Naoto; Sasaki, Kazuki

    2015-11-06

    Limited proteolysis is a pivotal mechanism regulating protein functions. Identifying physiologically or pathophysiologically relevant cleavage sites helps to develop molecular tools that can be used for diagnostics or therapeutics. During proteolysis of secretory and membrane proteins, part of the cleaved protein is liberated and destined to undergo degradation but should retain original cleavage sites created by proteolytic enzymes. We profiled endogenous peptides accumulated for 4 h in media conditioned by primary cultured rat cardiac fibroblasts. A total of 3916 redundant peptide sequences from 94 secretory proteins and membrane proteins served to identify limited cleavage sites, both annotated and unannotated, for signal peptide or propeptide removal, peptide hormone processing, ectodomain shedding, and regulated intramembrane proteolysis. Incorrectly predicted signal cleavage sites are found in typical proteins such as extracellular matrix proteins and the peptide hormone precursor adrenomedullin ADM. The revealed signal peptide cleavage site for ADM was experimentally verified by identifying the major molecular form of flanking proadrenomedullin N-terminal peptide. We suggest that profiling of endogenous peptides, like transcriptome sequence reads, makes sense in regular cells such as fibroblasts and that peptidomics provides insight into proteolysis-regulated protein functions.

  11. Transient Stability Improvement for Combined Heat and Power System Using Load Shedding

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Chen

    2014-01-01

    Full Text Available The purpose of the paper is to analyze and improve the transient stability of an industrial combined heat and power (CHP system in a high-tech science park in Taiwan. The CHP system installed two 161 kV/161 kV high-impendence transformers to connect with Taipower System (TPS for both decreasing the short-circuit fault current and increasing the fault critical clearing time. The transient stabilities of three types of operation modes in CHP units, 3G1S, 2G1S, and 1G1S, are analyzed. Under the 3G1S operation mode, the system frequency is immediately restored to 60 Hz after tie line tripping with the TPS. Under the 1G1S and 2G1S operation modes, the system frequencies will continuously decrease and eventually become unstable. A novel transient stability improvement approach using load shedding technique based on the change in frequency is proposed to improve the transient stability.

  12. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  13. Enhancement of Voltage Stability of DC Smart Grid During Islanded Mode by Load Shedding Scheme

    Science.gov (United States)

    Nassor, Thabit Salim; Senjyu, Tomonobu; Yona, Atsushi

    2015-10-01

    This paper presents the voltage stability of a DC smart grid based on renewable energy resources during grid connected and isolated modes. During the islanded mode the load shedding, based on the state of charge of the battery and distribution line voltage, was proposed for voltage stability and reservation of critical load power. The analyzed power system comprises a wind turbine, a photovoltaic generator, storage battery as controllable load, DC loads, and power converters. A fuzzy logic control strategy was applied for power consumption control of controllable loads and the grid-connected dual active bridge series resonant converters. The proposed DC Smart Grid operation has been verified by simulation using MATLAB® and PLECS® Blockset. The obtained results show the effectiveness of the proposed method.

  14. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears

    Directory of Open Access Journals (Sweden)

    Jonathan J. Miner

    2016-09-01

    Full Text Available Zika virus (ZIKV is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl−/−, Mertk−/−, and Axl−/−Mertk−/− double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

  15. Unsteady separation and vortex shedding from a laminar separation bubble over a bluff body

    Science.gov (United States)

    Das, S. P.; Srinivasan, U.; Arakeri, J. H.

    2013-07-01

    Boundary layers are subject to favorable and adverse pressure gradients because of both the temporal and spatial components of the pressure gradient. The adverse pressure gradient may cause the flow to separate. In a closed loop unsteady tunnel we have studied the initiation of separation in unsteady flow past a constriction (bluff body) in a channel. We have proposed two important scalings for the time when boundary layer separates. One is based on the local pressure gradient and the other is a convective time scale based on boundary layer parameters. The flow visualization using a dye injection technique shows the flow structure past the body. Nondimensional shedding frequency (Strouhal number) is calculated based on boundary layer and momentum thicknesses. Strouhal number based on the momentum thickness shows a close agreement with that for flat plate and circular cylinder.

  16. Tissue localization, shedding, virus carriage, antibody response, and aerosol transmission of porcine epidemic diarrhea virus (PEDV) following inoculation of 4 week-old feeder pigs

    Science.gov (United States)

    Porcine epidemic diarrhea virus (PEDV) emerged in the U.S. in April 2013 and caused significant losses to the swine industry. The purpose of this investigation was to determine tissue localization, shedding patterns, virus carriage, antibody response, and aerosol transmission of PEDV following inocu...

  17. Report on the investigation into the snagging of hooks and their indiscriminate shedding of slings/pennants. Phase 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    The Health and Safety Executive (HSE) initiated studies to (a) identify reasons why hooks snag on various objects and (b) into the unsolicited discharge or shedding of slings/pennants from non-loaded hooks during offshore operations with cranes. In practical testing, both Single Point Hooks and Load Closing Hooks were used. The author of the report has assumed the reader is familiar with the offshore environment and with the terminology associated with lifting equipment. The tests were recorded on video which is available from the HSE. The report includes various safety recommendations.

  18. Local Social and Environmental Impacts of Biofuels: Global Comparative Assessment and Implications for Governance

    Directory of Open Access Journals (Sweden)

    Laura German

    2011-12-01

    Full Text Available The 2000s witnessed the rapid expansion of biofuel plantations in the global South in the context of a growing trend of crop plantation expansion. This trend has been spurred by policies in the European Union, United States, Brazil, and other countries favoring the use of biofuels in the transport sector to enhance energy security and reduce carbon emissions, as well as by the desire of governments in developing countries to harness the stimulus that new commercial investments provide to the agricultural sector and to national economies. Despite these potential benefits, a number of concerns have been raised about the local social and environmental impacts of biofuel feedstock expansion. We shed light on this debate through a synthesis of findings from case studies in six biofuel producer countries of Asia, Africa, and Latin America, and a seventh paper exploring the implications of the land-use changes observed in these case studies for the climate mitigation potential of biofuels. We also explore the implications for governing the environmental impacts of biofuel feedstock production, protecting the rights of customary land users, and enabling smallholder-inclusive business models. Our analysis suggests that better governance of the sector's impacts is not the exclusive preserve of unitary sets of actors, but instead requires concerted and coordinated efforts by governments of producer and consumer countries, investors, civil society, and the financial sector to better capture the sector's potential while minimizing its social and environmental costs.

  19. Syndecans as modulators and potential pharmacological targets in cancer progression

    Directory of Open Access Journals (Sweden)

    Despoina eBarbouri

    2014-02-01

    Full Text Available Extracellular matrix (ECM components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs, a family of transmembrane heparan sulfate proteoglycans (HSPGs. Specifically, heparan sulfate (HS chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs, ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma.

  20. Longitudinal prevalence, oocyst shedding and molecular characterisation of Eimeria species in sheep across four states in Australia.

    Science.gov (United States)

    Yang, Rongchang; Jacobson, Caroline; Gardner, Graham; Carmichael, Ian; Campbell, Angus J D; Ryan, Una

    2014-10-01

    The prevalence of Eimeria in sheep in Australia has not been well described, therefore a quantitative PCR (qPCR) was developed, validated and used to study the prevalence and oocyst concentration in lamb faecal samples at three sampling periods (weaning, post-weaning and pre-slaughter) from eight farms across South Australia, New South Wales, Victoria and Western Australia. A total of 3412 faecal samples were collected from approximately 1182 lambs across the 4 states and screened for the presence of Eimeria using this qPCR at the 18S ribosomal RNA (rRNA) locus. A subset of positives was typed by sequence analysis at the 18S locus. The overall prevalence was 18.1% (95% CI 16.8-19.3%) and of the 616 positives, 118 were successfully genotyped. The prevalence of Eimeria was highest in NSW and peaked at 70% during the post-weaning period. The range of oocyst shedding per gram of faeces (g(-1)) at weaning, post-weaning and pre-slaughter overall across all states was 23-2.1×10(7), 23-1.3×10(7) and 23-2.1×10(5), respectively. Median Eimeria shedding g(-1) was higher during post-weaning (1.1×10(3)) and pre-slaughter (1.1×10(3)) than during weaning (206). The following species were identified: Eimeria crandallis, Eimeria ahsata, Eimeria ovinoidalis, Eimeria weybridgensis and Eimeria cylindrica. Of these, E. crandallis and E. ovinoidalis, the most pathogenic species in sheep were responsible for 58.5% of infections typed. This highlights a need for further research to quantify the production impacts of Eimeria in sheep. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

    Science.gov (United States)

    Chiva-Blanch, Gemma; Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Peña, Esther; Ybarra, Juan; Pou, Jose M; Badimon, Lina

    2016-07-01

    Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Investigating Ammonia Emission Sources in a Coastal Urban Air Shed Using Stable Isotope Techniques

    Science.gov (United States)

    Berner, A.; Felix, J. D. D.

    2017-12-01

    For nearly 100 years, mankind has met the food demands of a growing population by commercially producing and consuming reactive nitrogen fertilizers. So much so, that now 40-60% of the population relies on them. This increase has drastically altered the global nitrogen (N) cycle. Specifically, ammonia (NH3) emissions to the atmosphere have increased, resulting in wet and dry NHx (NH3 + NH4+) deposition products that can be substantial sources of N to sensitive ecosystems. Excess N can wreak havoc on these environments, causing soil acidification, water body eutrophication, and decreases in biodiversity. Despite these effects, NH3 remains generally unregulated in the U.S. Should policymakers elect to regulate NH3, quantification of NH3 emission sources and transport is essential. This has proven to be particularly difficult in urban regions, where ambient NH3 may result from local urban sources and/or NH3 transport from rural agricultural sources. The presented work investigates potential NH3 emission sources within a South Texas coastal urban air shed, Corpus Christi, TX, U.S.A. Previous work has shown an increasing fine particulate matter (PM2.5) trend within the region, which may be attributable to NH3 emissions from a variety of local sources, including vehicle traffic, shipping traffic, the petrochemical industry, and/or surrounding agricultural cropland and livestock. NH3 was collected monthly at a set of 8 sites within the Corpus Christi air shed, analyzed for NH3 concentration and N isotopic composition (d15N-NH3), and compared to known isotopic compositions of NH3 sources. Low and seasonally variable d15N-NH3 values are associated with varying agricultural sources (fertilizer, livestock waste, etc.), while higher and more seasonally constant d15N-NH3 values are associated with non-agricultural sources (vehicles, industry, etc.). Several other physical and chemical atmospheric components (e.g. SO2, NO2, O3, PM2.5, temperature, relative humidity) were also

  3. Effect of shed rooftype and babassu pie on the productive characteristics of meat quails

    Directory of Open Access Journals (Sweden)

    Jordane de Oliveira Borges

    2017-08-01

    Full Text Available We aimed to evaluate the effects of shed roof(SR typeand the inclusion of babassu pie (BP in rations on the productive characteristics ofmeat quailsfrom days 14 to 28 and days14 to 40. We studied 896 meatquails. The experimental design was completely randomized with a 4x4 factorial arrangement, using four types of shedroofs (fiber cement, ceramic, straw, and painted fiber cement and four rations (with 0, 5, 10, and 15% inclusion of babassu pie. The performance variables evaluated from 14 to 28 and 14 to 40 days included food intake (FI, g/bird, mean weight gain (WG, g/bird, food conversion (FC, g/g, mean live weight on day 28 (MW28, g/bird, mean live weight on day 40 (MW40, g/bird, and energy efficiency (EF; g Mcal. After slautherthe birds on day 40, we measured the carcass weight (CW and the carcass yield (CY, %, obtained for the breast (BY, legs (LGY, and wings (WINGY. We also obtained the relative weight of the heart (HRW, liver (LRW, gizzard (GRW, and intestine (IRW. To compare the economic efficiency between the experimental rations, we analyzed the cost of ration per kg of carcass (CC and determined the gross margin (GM. Between day 14 and day 28, we found that the use of SR influenced the FI28, WG28, and the MW28 of the quails (p 0.05, but it linearly improved WG28, FC28, MW28, and EF28. Between days 14 and 40, we found that SR influenced the WG40, FC40, MW40, and EF40 of the quails (p < 0.05 and that a BP increased the FI40, WG40, and MW40 in a quadratic manner. SR and BP did not affect the CW, BY, WINGY, LGY, HRW, LRW,or IRW. However, BP influenced MGRW, which increased linearly with the inclusion of BP. We concluded that a ceramic roof provides better environmental conditions than do other shed roofs. The inclusion of BP improved the performance characteristics, and it was technically feasible to include up to 15% BP in the rations of meat quails. Based on the current cost analysis, however, the inclusion of BP is economically

  4. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

    Science.gov (United States)

    Lopes-Pacheco, Miquéias

    2016-01-01

    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  5. Quantitative assessment of faecal shedding of β-lactam-resistant Escherichia coli and enterococci in dogs

    DEFF Research Database (Denmark)

    Gongora, Carmen Espinosa; Shah, Syed Qaswar Ali; Jessen, Lisbeth Rem

    2015-01-01

    Quantitative data on faecal shedding of antimicrobial resistant bacteria are crucial to assess the risk of transmission from dogs to other animals as well as humans. In this study we investigated prevalence and concentrations of β-lactam-resistant Escherichia coli and enterococci in the faeces...... of 108 dogs presenting at a veterinary hospital in Denmark. The dogs had not been treated with antimicrobials for 4 weeks prior to the study. Total E. coli and enterococci were quantified by counts on MacConkey and Slanetz-Bartley, respectively. Resistant E. coli and enterococci were counted on the same...... media containing relevant antibiotic concentrations, followed by species identification using MALDI-TOF. Ampicillin- and cefotaxime-resistant E. coli were detected in 40% and 8% of the dogs, respectively, whereas approximately 15% carried ampicillin-resistant enterococci, mainly Enterococcus faecium...

  6. Cross-domain inhibition of TACE ectodomain

    DEFF Research Database (Denmark)

    Tape, Christopher J; Willems, Sofie H; Dombernowsky, Sarah L

    2011-01-01

    Proteolytic release from the cell surface is an essential activation event for many growth factors and cytokines. TNF-a converting enzyme (TACE) is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates and is an attractive therapeutic...

  7. Same but different: Comparative modes of information processing are implicated in the construction of perceptions of autonomy support.

    Science.gov (United States)

    Lee, Rebecca Rachael; Chatzisarantis, Nikos L D

    2017-11-01

    An implicit assumption behind tenets of self-determination theory is that perceptions of autonomy support are a function of absolute modes of information processing. In this study, we examined whether comparative modes of information processing were implicated in the construction of perceptions of autonomy support. In an experimental study, we demonstrated that participants employed comparative modes of information processing in evaluating receipt of small, but not large, amounts of autonomy support. In addition, we found that social comparison processes influenced a number of outcomes that are empirically related to perceived autonomy support such as sense of autonomy, positive affect, perceived usefulness, and effort. Findings shed new light upon the processes underpinning construction of perceptions related to autonomy support and yield new insights into how to increase the predictive validity of models that use autonomy support as a determinant of motivation and psychological well-being. © 2017 The British Psychological Society.

  8. Examination of virus shedding in semen from vaccinated and from previously infected boars after experimental challenge with porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Nielsen, Thomas L.; Nielsen, Jens; Have, Per

    1997-01-01

    to the Danish pig industry. The use of a vaccination-program may be a way to avoid or reduce the problem, This study evaluates the use of two vaccines: One live, attenuated vaccine and one inactivated vaccine, A pronounced reduction in viremia and shedding of virus in semen was demonstrated by use of the live...

  9. Selective decentralized underfrequency protection. Load shedding depending on underfrequency; Selektiver dezentraler Unterfrequenzschutz. Unterfrequenzabhaengiger Lastabwurf

    Energy Technology Data Exchange (ETDEWEB)

    Worgull, Alexander; Horenkamp, Willi; Kaliwoda, Michael; Rehtanz, Christian [Technische Univ. Dortmund (Germany). Inst. fuer Energiesysteme, Energieeffizienz und Energiewirtschaft

    2013-03-11

    In the case of major disruptions, the underfrequency depending load shedding serves to restore the performance balance between generation and consumption. If a switching off of electrical consumers due to an actual underfrequency event is required, individual grid areas are separated from the residual power grid by means of a frequency relay. Normally, the disconnection from the mains takes place at the medium voltage level of the 110 kV transformer. In addition to consumers, also decentralized energy transformation plants are disconnected. Thus, the performance deficit will be enhanced, if necessary. Thus, a procedure considering the actual load situation and feed-in situation is absolutely essential in the future. The Institute of Energy Systems, Energy Efficiency and Energy Economics at the Dortmund Technical University (Dortmund, Federal Republic of Germany) develops which realizes a future-oriented selective underfrequency protection by means of smart metering systems.

  10. Vortex shedding control of circular cylinder by perforated shroud in deep water

    Directory of Open Access Journals (Sweden)

    Ozkan Gokturk M.

    2017-01-01

    Full Text Available The aim of the present study is to control the vortex shedding downstream of a circular cylinder (inner cylinder by the existence of outer perforated cylinder concentrically located around the inner cylinder in deep water. The flow characteristics downstream of concentrically placed coupled cylinders were investigated quantitatively by the Particle Image Velocimetry (PIV technique. Diameter of the outer perforated cylinder and inner cylinder were kept constant as Do=100 mm and Di=50 mm. The depth-averaged free-stream velocity was also kept constant as U=100 mm/s which corresponded to the Reynolds number of ReDo=10,000 based on the outer cylinder diameter. Experiments were conducted for six porosities (β = 0.3, 0.4, 0.5, 0.6, 0.7 and 0.8 in order to show the effect of these parameters on the flow control. Maximum values of both Reynolds shear stress, and turbulence kinetic energy, significantly decreased with the existence of outer perforated cylinder and also, the location of peak magnitudes of turbulence statistics occurred at locations further downstream compared to the bare cylinder case. The most effective control was revealed for the porosity of β=0.7.

  11. Vortex shedding control of circular cylinder by perforated shroud in deep water

    Science.gov (United States)

    Ozkan, Gokturk M.; Durhasan, Tahir; Pinar, Engin; Aksoy, Muhammed M.; Akilli, Huseyin; Sahin, Beşir

    The aim of the present study is to control the vortex shedding downstream of a circular cylinder (inner cylinder) by the existence of outer perforated cylinder concentrically located around the inner cylinder in deep water. The flow characteristics downstream of concentrically placed coupled cylinders were investigated quantitatively by the Particle Image Velocimetry (PIV) technique. Diameter of the outer perforated cylinder and inner cylinder were kept constant as Do=100 mm and Di=50 mm. The depth-averaged free-stream velocity was also kept constant as U=100 mm/s which corresponded to the Reynolds number of ReDo=10,000 based on the outer cylinder diameter. Experiments were conducted for six porosities (β = 0.3, 0.4, 0.5, 0.6, 0.7 and 0.8) in order to show the effect of these parameters on the flow control. Maximum values of both Reynolds shear stress, and turbulence kinetic energy, significantly decreased with the existence of outer perforated cylinder and also, the location of peak magnitudes of turbulence statistics occurred at locations further downstream compared to the bare cylinder case. The most effective control was revealed for the porosity of β=0.7.

  12. Lignans from the shed trunk barks of the critically endangered plant Abies beshanzuensis and their anti-neuroinflammatory activities.

    Science.gov (United States)

    Hu, Chang-Ling; Xiong, Juan; Xu, Peng; Cheng, Ke-Jun; Yang, Guo-Xun; Hu, Jin-Feng

    2017-06-01

    During a further and comprehensive phytochemical investigation on the shed trunk barks of the critically endangered plant Abies beshanzuensis, one new (1) and ten known (2-11) lignans with diverse structures were isolated. On the basis of spectroscopic methods, the new structure was established to be (7S,8R,8'R)-4'-methoxyl-α-conidendrin (1). Among the isolated lignans, (-)-matairesinol (5) and (-)-arctigenin (6) showed significant anti-neuroinflammatory activities by inhibiting the overproduction of nitric oxide in lipopolysaccharide-stimulated murine BV-2 microglial cells, with IC 50 values of 11.5 and 19.0 μM, respectively.

  13. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

    Science.gov (United States)

    Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Allogeneic stem cells derived from human exfoliated deciduous teeth (SHED for the management of periapical lesions in permanent teeth: Two case reports of a novel biologic alternative treatment

    Directory of Open Access Journals (Sweden)

    Madu Ghana Shyam Prasad

    2017-06-01

    Full Text Available Stem cells are the pluripotent cells that have the capacity to differentiate into other specialized cells. Recently, many experiments have been conducted to study the potentiality of stem cells in the tissue regeneration. We report two cases treated utilizing stem cells from human exfoliated deciduous teeth (SHED in the management of periapical lesions in permanent teeth. Two normal human deciduous teeth from children, 7‒8 years of age, were collected to isolate stem cells. Two patients, one with periapical pathology alone and the other with periapical lesion along with an open apex in young permanent teeth, were selected for the study. After initial debridement of the root canals, homing of SHED was carried out and the access cavity was sealed using glass-ionomer cement. Clinical examination after 7 days, 30 days, 90 days, 180 days and 365 days revealed no symptoms. Closure of open apex and periapical tissue healing were observed radiographically at one-month review and maintained until 365-day review. Positive response to electric pulp testing was recorded for the treated teeth from the 3- to 12-month follow-ups. The treated cases demonstrated complete resolution of periapical radiolucency in a span of 30 days, which was faster than the conventional methods. SHED could be considred effective in treating the periapical lesions and open apex in permanent teeth.

  15. The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K

    Energy Technology Data Exchange (ETDEWEB)

    Verdino, Petra; Witherden, Deborah A.; Havran, Wendy L.; Wilson, Ian A. (Scripps)

    2010-11-15

    Coxsackie and adenovirus receptor (CAR) is the primary cellular receptor for group B coxsackieviruses and most adenovirus serotypes and plays a crucial role in adenoviral gene therapy. Recent discovery of the interaction between junctional adhesion molecule-like protein (JAML) and CAR uncovered important functional roles in immunity, inflammation, and tissue homeostasis. Crystal structures of JAML ectodomain (2.2 angstroms) and its complex with CAR (2.8 angstroms) reveal an unusual immunoglobulin-domain assembly for JAML and a charged interface that confers high specificity. Biochemical and mutagenesis studies illustrate how CAR-mediated clustering of JAML recruits phosphoinositide 3-kinase (P13K) to a JAML intracellular sequence motif as delineated for the {alpha}{beta} T cell costimulatory receptor CD28. Thus, CAR and JAML are cell signaling receptors of the immune system with implications for asthma, cancer, and chronic nonhealing wounds.

  16. Interactions of the Hindgut Mucosa-Associated Microbiome with Its Host Regulate Shedding of Escherichia coli O157:H7 by Cattle.

    Science.gov (United States)

    Wang, Ou; McAllister, Tim A; Plastow, Graham; Stanford, Kim; Selinger, Brent; Guan, Le Luo

    2018-01-01

    Cattle are the primary carrier of Escherichia coli O157:H7, a foodborne human pathogen, and those shedding >10 4 CFU/gram of feces of E. coli O157:H7 are defined as supershedders (SS). This study investigated the rectoanal junction (RAJ) mucosa-associated microbiota and its relationship with host gene expression in SS and in cattle from which E. coli O157:H7 was not detected (nonshedders [NS]), aiming to elucidate the mechanisms involved in supershedding. In total, 14 phyla, 66 families, and 101 genera of RAJ mucosa-associated bacteria were identified and Firmicutes (61.5 ± 7.5%), Bacteroidetes (27.9 ± 6.4%), and Proteobacteria (5.5 ± 2.1%) were the predominant phyla. Differential abundance analysis of operational taxonomic units (OTUs) identified 2 OTUs unique to SS which were members of Bacteroides and Clostridium and 7 OTUs unique to NS which were members of Coprococcus , Prevotella , Clostridium , and Paludibacter Differential abundance analysis of predicted microbial functions (using PICRUSt [phylogenetic investigation of communities by reconstruction of unobserved states]) revealed that 3 pathways had higher abundance (log 2 fold change, 0.10 to 0.23) whereas 12 pathways had lower abundance (log 2 fold change, -0.36 to -0.20) in SS. In addition, we identified significant correlations between expression of 19 differentially expressed genes and the relative abundance of predicted microbial functions, including nucleic acid polymerization and carbohydrate and amino acid metabolism. Our findings suggest that differences in RAJ microbiota at both the compositional and functional levels may be associated with E. coli O157:H7 supershedding and that certain microbial groups and microbial functions may influence RAJ physiology of SS by affecting host gene expression. IMPORTANCE Cattle with fecal E. coli O157:H7 at >10 4 CFU per gram of feces have been defined as the supershedders, and they are responsible for the most of the E. coli O157:H7 spread into farm

  17. A study on the frictional response of reptilian shed skin

    International Nuclear Information System (INIS)

    Abdel-Aal, H A; Vargiolu, R; Zahouani, H; Mansori, M El

    2011-01-01

    Deterministic surfaces are constructs of which profile, topography and textures are integral to the function of the system they enclose. They are designed to yield a predetermined tribological response. Developing such entities relies on controlling the structure of the rubbing interface so that, not only the surface is of optimized topography, but also is able to self-adjust its tribological behaviour according to the evolution of sliding conditions. In seeking inspirations for such designs, many engineers are turning toward the biological world to study the construction and behaviour of bio-analogues, and to probe the role surface topography assumes in conditioning of frictional response. That is how a bio-analogue can self-adjust its tribological response to adapt to habitat constraints. From a tribological point of view, Squamate Reptiles, offer diverse examples where surface texturing, submicron and nano-scale features, achieves frictional regulation. In this paper, we study the frictional response of shed skin obtained from a snake (Python regius). The study employed a specially designed tribo-acoustic probe capable of measuring the coefficient of friction and detecting the acoustical behavior of the skin in vivo. The results confirm the anisotropy of the frictional response of snakes. The coefficient of friction depends on the direction of sliding: the value in forward motion is lower than that in the backward direction. Diagonal and side winding motion induces a different value of the friction coefficient. We discuss the origin of such a phenomenon in relation to surface texturing and study the energy constraints, implied by anisotropic friction, on the motion of the reptile.

  18. A study on the frictional response of reptilian shed skin

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Aal, H A [Arts et Metier ParisTech, Rue Saint Dominique BP 508, 51006 Chalons-en-Champagne (France); Vargiolu, R; Zahouani, H [Laboratoire de Tribology et Dynamique des Systemes, UMR CNRS 5513, ENI Saint Etienne - Ecole Centrale de Lyon -36 Avenue Guy de Collongue, 69131 Ecully cedex. France (France); Mansori, M El, E-mail: Hisham.abdel-aal@ensam.eu [Ecole Nationale Superieure d' Arts et Metiers, 2, cours des Arts et Metiers - 13617 Aix en Provence cedex 1 (France)

    2011-08-19

    Deterministic surfaces are constructs of which profile, topography and textures are integral to the function of the system they enclose. They are designed to yield a predetermined tribological response. Developing such entities relies on controlling the structure of the rubbing interface so that, not only the surface is of optimized topography, but also is able to self-adjust its tribological behaviour according to the evolution of sliding conditions. In seeking inspirations for such designs, many engineers are turning toward the biological world to study the construction and behaviour of bio-analogues, and to probe the role surface topography assumes in conditioning of frictional response. That is how a bio-analogue can self-adjust its tribological response to adapt to habitat constraints. From a tribological point of view, Squamate Reptiles, offer diverse examples where surface texturing, submicron and nano-scale features, achieves frictional regulation. In this paper, we study the frictional response of shed skin obtained from a snake (Python regius). The study employed a specially designed tribo-acoustic probe capable of measuring the coefficient of friction and detecting the acoustical behavior of the skin in vivo. The results confirm the anisotropy of the frictional response of snakes. The coefficient of friction depends on the direction of sliding: the value in forward motion is lower than that in the backward direction. Diagonal and side winding motion induces a different value of the friction coefficient. We discuss the origin of such a phenomenon in relation to surface texturing and study the energy constraints, implied by anisotropic friction, on the motion of the reptile.

  19. A compact, multifunctional fusion module directs cholesterol-dependent homomultimerization and syncytiogenic efficiency of reovirus p10 FAST proteins.

    Directory of Open Access Journals (Sweden)

    Tim Key

    2014-03-01

    Full Text Available The homologous p10 fusion-associated small transmembrane (FAST proteins of the avian (ARV and Nelson Bay (NBV reoviruses are the smallest known viral membrane fusion proteins, and are virulence determinants of the fusogenic reoviruses. The small size of FAST proteins is incompatible with the paradigmatic membrane fusion pathway proposed for enveloped viral fusion proteins. Understanding how these diminutive viral fusogens mediate the complex process of membrane fusion is therefore of considerable interest, from both the pathogenesis and mechanism-of-action perspectives. Using chimeric ARV/NBV p10 constructs, the 36-40-residue ectodomain was identified as the major determinant of the differing fusion efficiencies of these homologous p10 proteins. Extensive mutagenic analysis determined the ectodomain comprises two distinct, essential functional motifs. Syncytiogenesis assays, thiol-specific surface biotinylation, and liposome lipid mixing assays identified an ∼25-residue, N-terminal motif that dictates formation of a cystine loop fusion peptide in both ARV and NBV p10. Surface immunofluorescence staining, FRET analysis and cholesterol depletion/repletion studies determined the cystine loop motif is connected through a two-residue linker to a 13-residue membrane-proximal ectodomain region (MPER. The MPER constitutes a second, independent motif governing reversible, cholesterol-dependent assembly of p10 multimers in the plasma membrane. Results further indicate that: (1 ARV and NBV homomultimers segregate to distinct, cholesterol-dependent microdomains in the plasma membrane; (2 p10 homomultimerization and cholesterol-dependent microdomain localization are co-dependent; and (3 the four juxtamembrane MPER residues present in the multimerization motif dictate species-specific microdomain association and homomultimerization. The p10 ectodomain therefore constitutes a remarkably compact, multifunctional fusion module that directs syncytiogenic

  20. Dynamics of virus shedding and in situ confirmation of chelonid herpesvirus 5 in Hawaiian green turtles with Fibropapillomatosis

    Science.gov (United States)

    Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Schettle, Nelli; Ackermann, Mathias

    2015-01-01

    Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5.

  1. Dynamics of Virus Shedding and In Situ Confirmation of Chelonid Herpesvirus 5 in Hawaiian Green Turtles With Fibropapillomatosis.

    Science.gov (United States)

    Work, T M; Dagenais, J; Balazs, G H; Schettle, N; Ackermann, M

    2015-11-01

    Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5. © The Author(s) 2014.

  2. Development of a pressure based vortex-shedding meter: measuring unsteady mass-flow in variable density gases

    International Nuclear Information System (INIS)

    Ford, C L; Winroth, M; Alfredsson, P H

    2016-01-01

    An entirely pressure-based vortex-shedding meter has been designed for use in practical time-dependent flows. The meter is capable of measuring mass-flow rate in variable density gases in spite of the fact that fluid temperature is not directly measured. Unlike other vortex meters, a pressure based meter is incredibly robust and may be used in industrial type flows; an environment wholly unsuitable for hot-wires for example. The meter has been tested in a number of static and dynamic flow cases, across a range of mass-flow rates and pressures. The accuracy of the meter is typically better than about 3% in a static flow and resolves the fluctuating mass-flow with an accuracy that is better than or equivalent to a hot-wire method. (paper)

  3. Effect of a nutritional reconditioning program for thin dairy cattle on body weight, carcass quality, and fecal pathogen shedding.

    Science.gov (United States)

    Maier, Gabriele U; Hoar, Bruce R; Stull, Carolyn L; Kass, Philip H; Villanueva, Veronica; Maas, John

    2011-12-15

    To assess changes in body weight, carcass quality, and fecal pathogen shedding in cull dairy cows fed a high-energy ration for 28 or 56 days prior to slaughter. Randomized clinical trial. 31 adult Holstein dairy cows. Cows were randomly assigned to a control (immediate slaughter) group or a 28-day or 56-day feeding group. Cows in the feeding groups received a high-energy feed and were weighed every 7 days. Carcasses were evaluated by USDA employees. Fecal and blood samples were collected at the start and end of the feeding periods. Body condition score and adjusted preliminary yield grade were significantly increased in both feeding groups, compared with values for the control group; body weight, hot carcass weight, dressing percentage, and ribeye area were significantly increased after 56 days, but not after 28 days, compared with values for the control group. Average daily gain and marbling score were significantly lower after feeding for 28 days versus after 56 days. Prevalence of Escherichia coli O157:H7 shedding in feces decreased from 14% to 5.6%, but this difference was not significant. Cows seropositive for antibodies against bovine leukemia virus that had signs of lymphoma and lame cows had a low average daily gain. Net loss was $71.32/cow and $112.80/cow for the 28-day and 56-day feeding groups, respectively. Feeding market dairy cows improved body condition and carcass quality. Cows seropositive for antibodies against bovine leukemia virus that have signs of lymphoma and lame cows might be poor candidates for reconditioning.

  4. H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast Cancer.

    Science.gov (United States)

    Itai, Shunsuke; Fujii, Yuki; Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Chang, Yao-Wen; Handa, Saori; Takahashi, Maki; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

    2017-08-01

    Human epidermal growth factor receptor 2 (HER2) plays a critical role in the progression of breast cancers, and HER2 overexpression is associated with poor clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to significant survival benefits in patients with HER2-positive metastatic breast cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. Initially, we expressed the full length or ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme-linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical analyses (fourth screening). Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and clone H 2 Mab-77 (IgG 1 , kappa) was selected. Finally, immunohistochemical analyses with H 2 Mab-77 showed sensitive and specific reactions against breast cancer cells, warranting the use of H 2 Mab-77 to detect HER2 in pathological analyses of breast cancers.

  5. Men's perspectives on fall risk and fall prevention following participation in a group-based programme conducted at Men's Sheds, Australia.

    Science.gov (United States)

    Liddle, Jeannine L M; Lovarini, Meryl; Clemson, Lindy M; Jang, Haeyoung; Willis, Karen; Lord, Stephen R; Sherrington, Catherine

    2017-05-01

    Research on older men's views regarding fall prevention is limited. The purpose of this qualitative study was to explore the experiences and perspectives of older men regarding fall risk and prevention so that fall prevention programmes can better engage older men. Eleven men who had taken part in a group-based fall prevention programme called Stepping On conducted at Men's Sheds in Sydney, Australia, participated in semi-structured interviews during June and July 2015 which were audio-recorded and transcribed. Data were coded and analysed using constant comparative methods. Over-arching theoretical categories were developed into a conceptual framework linking programme context and content with effects of programme participation on men. Men's Sheds facilitated participation in the programme by being inclusive, male-friendly places, where Stepping On was programmed into regular activities and was conducted in an enjoyable, supportive atmosphere. Programme content challenged participants to think differently about themselves and their personal fall risk, and provided practical options to address fall risk. Two major themes were identified: adjusting the mindset where men adopted a more cautious mindset paying greater attention to potential fall risks, being careful, concentrating and slowing down; and changing the ways where men acted purposefully on environmental hazards at home and incorporated fall prevention exercises into their routine schedules. Practitioners can engage and support older men to address falls by better understanding men's perspectives on personal fall risk and motivations for action. © 2016 John Wiley & Sons Ltd.

  6. Understanding farmers' strategic decision-making processes and the implications for biodiversity conservation policy.

    Science.gov (United States)

    Farmar-Bowers, Quentin; Lane, Ruth

    2009-02-01

    The conservation of biodiversity is an important issue world wide and in Australia the maintenance of native biodiversity on farms makes an important contribution to overall conservation objectives. This paper seeks to explain Australian farmers' rationale for maintaining biodiversity on their farms for personal as opposed to business reasons by developing a decision-systems theory from in-depth interviews. This difference has implications for policy development. The decision-systems theory is divided into two main sections. The first section contains five parts. (1) A hierarchy of motivation stories, (2) the concept of suitability and availability of opportunities, (3) a hierarchy of three decision-systems, (4) the concept of personal career paths, (5) the concept of Lenses. The second section contains one part, a policy classification system called 'boxes of influence' that suggests how policy developers can use the information in the first section to develop new biodiversity conservation policy. The paper suggests that decision-systems theory could be used to shed new light on current trends in agriculture and become an important investigative tool for policy development concerning the conservation of biodiversity on farms.

  7. Inflammation et immunité : implications dans l’obésité et le diabète de type 2

    Directory of Open Access Journals (Sweden)

    Akhtar Khan Naim

    2006-09-01

    Full Text Available The evidences have been increasingly accumulated on the implication of inflammatory mediators like tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 in the pathological states related to insulin resistance like obesity, type 2 diabetes and atherosclerosis. There seems a link between insulin resistance and these pro-inflammatory agents, secreted by macrophages and adipocytes. Th (helper cells are differentiated into either Th1 or Th2 phenotypes. It is generally considered that Th1 phenotype is pro-inflammatory whereas Th2 phenotype exerts anti-inflammatory (protective effects. The upregulation of Th1 phenotype may aggravate these pathologies. One of the adipokines, i.e., adiponectin, and insulin act as anti-inflammatory agents. Insulin also favours the differentiation of Th cells into Th2 phenotype. TNF-α and IL-6 might counter balance the action of insulin by interfering with insulin receptor signalling in these pathological situations. The agonists of PPARα and PPARγ, and n-3 polyunsaturated fatty acids may exert an anti-inflammatory effect by shifting Th1/Th2 balance to Th2 phenotype. The factors, implicated in the secretion of inflammatory mediators are not well known, though the role of glucose-induced oxidative stress has been underlined. In this article, we shed light on the cross-talk between pro- and anti-inflammatory agents in these patho-physiological states related to insulin resistance.

  8. Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis

    DEFF Research Database (Denmark)

    Fabriek, Babs O; Møller, Holger J; Vloet, Rianka P M

    2007-01-01

    The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP...

  9. Genetic makeup of Shiga toxin-producing Escherichia coli in relation to clinical symptoms and duration of shedding: a microarray analysis of isolates from Swedish children.

    Science.gov (United States)

    Matussek, A; Jernberg, C; Einemo, I-M; Monecke, S; Ehricht, R; Engelmann, I; Löfgren, S; Mernelius, S

    2017-08-01

    Shiga toxin (Stx)-producing Escherichia coli (STECs) cause non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome, and are the primary cause of acute renal failure in children worldwide. This study investigated the correlation of genetic makeup of STEC strains as revealed by DNA microarray to clinical symptoms and the duration of STEC shedding. All STEC isolated (n = 96) from patients <10 years of age in Jönköping County, Sweden from 2003 to 2015 were included. Isolates were characterized by DNA microarray, including almost 280 genes. Clinical data were collected through a questionnaire and by reviewing medical records. Of the 96 virulence genes (including stx) in the microarray, 62 genes were present in at least one isolate. Statistically significant differences in prevalence were observed for 21 genes when comparing patients with bloody diarrhea (BD) and with non-bloody stool (18 of 21 associated with BD). Most genes encode toxins (e.g., stx2 alleles, astA, toxB), adhesion factors (i.e. espB_O157, tir, eae), or secretion factors (e.g., espA, espF, espJ, etpD, nleA, nleB, nleC, tccP). Seven genes were associated with prolonged stx shedding; the presence of three genes (lpfA, senB, and stx1) and the absence of four genes (espB_O157, espF, astA, and intI1). We found STEC genes that might predict severe disease outcome already at diagnosis. This can be used to develop diagnostic tools for risk assessment of disease outcome. Furthermore, genes associated with the duration of stx shedding were detected, enabling a possible better prediction of length of STEC carriage after infection.

  10. Unsteady flow challenges tracking performance at vortex shedding frequencies without disrupting lift mechanisms

    Science.gov (United States)

    Matthews, Megan; Sponberg, Simon

    2017-11-01

    Birds, insects, and many animals use unsteady aerodynamic mechanisms to achieve stable hovering flight. Natural environments are often characterized by unsteady flows causing animals to dynamically respond to perturbations while performing complex tasks, such as foraging. Little is known about how unsteady flow around an animal interacts with already unsteady flow in the environment or how this impacts performance. We study how the environment impacts maneuverability to reveal any coupling between body dynamics and aerodynamics for hawkmoths, Manduca sexta,tracking a 3D-printed robotic flower in a wind tunnel. We also observe the leading-edge vortex (LEV), a known lift-generating mechanism for insect flight with smoke visualization. Moths in still and unsteady air exhibit near perfect tracking at low frequencies, but tracking in the flower wake results in larger overshoot at mid-range. Smoke visualization of the flower wake shows that the dominant vortex shedding corresponds to the same frequency band as the increased overshoot. Despite the large effect on flight dynamics, the LEV remains bound to the wing and thorax throughout the wingstroke. In general, unsteady wind seems to decrease maneuverability, but LEV stability seems decoupled from changes in flight dynamics.

  11. Angiotensin converting enzyme (ACE and ACE2 bind integrins and ACE2 regulates integrin signalling.

    Directory of Open Access Journals (Sweden)

    Nicola E Clarke

    Full Text Available The angiotensin converting enzymes (ACEs are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2 is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.

  12. Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    Directory of Open Access Journals (Sweden)

    Erhard van der Vries

    Full Text Available Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15% cases with prolonged 2009 pandemic virus replication (longer than 14 days, despite antiviral therapy. In 5 out of these 11 (45% cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

  13. Strategic issues and implications for the refining and marketing sector

    International Nuclear Information System (INIS)

    Jeffe, R.A.

    1995-01-01

    Refiners have faced a challenging business environment for the past decade. During this period, the industry has made approximately $25 billion of capital expenditures primarily to comply with increased governmental mandates, faced highly volatile petroleum product prices and garnered a return to equity of only 5%. While worldwide and US refining capacity has been flat in recent years, demand for refined petroleum products has been on the upswing and domestic supplies have also increased due to improved US capacity utilization rates (76% in 1984 and 93% in 1994) and increased imports (gasoline sales up 11% since 1984). The result has been highly volatile and generally weak refining margins (net Gulf Coast crack spread ranging from ($.95)/bbl in 1984 to $1.84/bbl in 1990 and averaging $.81/bbl since 1984). In response to the sustained difficulties in the marketplace, one has recently witnessed some strategic realignment in the industry. Several of the integrated companies, frustrated with the required capital expenditures and meager returns, have decided to shed non-core, non-strategic refining assets. For the most part, these assets have been bought by independents at, by historical measures, very attractive terms. This paper will provide an overview of the economics of the refining business, discuss the recent trends in refinery M and A activity and summarize possible implications of the recent strategic realignment

  14. Dissipative flow and vortex shedding in the Painleve boundary layer of a Bose-Einstein condensate

    International Nuclear Information System (INIS)

    Aftalion, Amandine; Du Qiang; Pomeau, Yves

    2003-01-01

    This paper addresses the drag force and formation of vortices in the boundary layer of a Bose-Einstein condensate stirred by a laser beam following the experiments of C. Raman et al., Phys. Rev. Lett. 83, 2502 (1999)10.1103/PhysRevLett.83.2502. We make our analysis in the frame moving at constant speed where the beam is fixed. We find that there is always a drag around the laser beam. We also analyze the mechanism of vortex nucleation. At low velocity, there are no vortices and the drag has its origin in a wakelike phenomenon: This is a particularity of trapped systems since the density gets small in an extended region. The shedding of vortices starts only at a threshold velocity and is responsible for a large increase in drag. This critical velocity for vortex nucleation is lower than the critical velocity computed for the corresponding 2D problem at the center of the cloud

  15. The placenta shed from goats with classical scrapie is infectious to goat kids and lambs.

    Science.gov (United States)

    Schneider, David A; Madsen-Bouterse, Sally A; Zhuang, Dongyue; Truscott, Thomas C; Dassanayake, Rohana P; O'Rourke, Katherine I

    2015-08-01

    The placenta of domestic sheep plays a key role in horizontal transmission of classical scrapie. Domestic goats are frequently raised with sheep and are susceptible to classical scrapie, yet potential routes of transmission from goats to sheep are not fully defined. Sparse accumulation of disease-associated prion protein in cotyledons casts doubt about the role of the goat's placenta. Thus, relevant to mixed-herd management and scrapie-eradication efforts worldwide, we determined if the goat's placenta contains prions orally infectious to goat kids and lambs. A pooled cotyledon homogenate, prepared from the shed placenta of a goat with naturally acquired classical scrapie disease, was used to orally inoculate scrapie-naïve prion genotype-matched goat kids and scrapie-susceptible lambs raised separately in a scrapie-free environment. Transmission was detected in all four goats and in two of four sheep, which importantly identifies the goat's placenta as a risk for horizontal transmission to sheep and other goats.

  16. Epidemiology of Salmonella sp. in California cull dairy cattle: prevalence of fecal shedding and diagnostic accuracy of pooled enriched broth culture of fecal samples

    Directory of Open Access Journals (Sweden)

    Omran A. Abu Aboud

    2016-08-01

    Full Text Available Background The primary objective of this cross-sectional study was to estimate the crude, seasonal and cull-reason stratified prevalence of Salmonella fecal shedding in cull dairy cattle on seven California dairies. A secondary objective was to estimate and compare the relative sensitivity (Se and specificity (Sp for pools of 5 and 10 enriched broth cultures of fecal samples for Salmonella sp. detection. Methods Seven dairy farms located in the San Joaquin Valley of California were identified and enrolled in the study as a convenience sample. Cull cows were identified for fecal sampling once during each season between 2014 and 2015, specifically during spring, summer, fall, and winter, and 10 cows were randomly selected for fecal sampling at the day of their sale. In addition, study personnel completed a survey based on responses of the herd manager to questions related to the previous four month’s herd management. Fecal samples were frozen until testing for Salmonella. After overnight enrichment in liquid broth, pools of enrichment broth (EBP were created for 5 and 10 samples. All individual and pooled broths were cultured on selective media with putative Salmonella colonies confirmed by biochemical testing before being serogrouped and serotyped. Results A total of 249 cull cows were enrolled into the study and their fecal samples tested for Salmonella. The survey-weighted period prevalence of fecal shedding of all Salmonella sp. in the cull cow samples across all study herds and the entire study period was 3.42% (N = 249; SE 1.07. The within herd prevalence of Salmonella shed in feces did not differ over the four study seasons (P = 0.074. The Se of culture of EBP of five samples was 62.5% (SE = 17.12, which was not statistically different from the Se of culture of EBP of 10 (37.5%, SE = 17.12, P = 0.48. The Sp of culture of EBP of five samples was 95.24% (SE = 3.29 and for pools of 10 samples was 100.00% (SE = 0. There was no statistical

  17. A PROBABILISTIC EXPOSURE ASSESSMENT FOR CHILDREN WHO CONTACT CCA-TREATED PLAYSETS AND DECKS USING THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION (SHEDS) MODEL FOR THE WOOD PRESERVATIVE EXPOSURE SCENARIO

    Science.gov (United States)

    The U.S. Environmental Protection Agency has conducted a probabilistic exposure and dose assessment on the arsenic (As) and chromium (Cr) components of Chromated Copper Arsenate (CCA) using the Stochastic Human Exposure and Dose Simulation model for wood preservatives (SHEDS-Wood...

  18. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

    Directory of Open Access Journals (Sweden)

    Joep P M Derikx

    Full Text Available BACKGROUND: Intestinal ischemia-reperfusion (IR is a phenomenon related to physiological conditions (e.g. exercise, stress and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery. Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time. METHODS AND FINDINGS: In 30 patients undergoing pancreatico-duodenectomy we took advantage of the fact that in this procedure a variable length of jejunum is removed. Isolated jejunum (5 cm was subjected to 30 minutes ischemia followed by reperfusion. Intestinal Fatty Acid Binding Protein (I-FABP arteriovenous concentration differences across the bowel segment were measured before and after ischemia to assess epithelial cell damage. Tissue sections were collected after ischemia and at 25, 60 and 120 minutes reperfusion and stained with H&E, and for I-FABP and the apoptosis marker M30. Bonferroni's test was used to compare I-FABP differences. Mean (SEM arteriovenous concentration gradients of I-FABP across the jejunum revealed rapidly developing epithelial cell damage. I-FABP release significantly increased from 290 (46 pg/ml before ischemia towards 3,997 (554 pg/ml immediately after ischemia (p<0.001 and declined gradually to 1,143 (237 pg/ml within 1 hour reperfusion (p<0.001. Directly after ischemia the intestinal epithelial lining was microscopically normal, while subepithelial spaces appeared at the villus tip. However, after 25 minutes reperfusion, enterocyte M30 immunostaining was observed at the villus tip accompanied by shedding of mature enterocytes into the lumen and loss of I-FABP staining. Interestingly, within 60 minutes reperfusion the epithelial barrier resealed, while debris of apoptotic, shedded epithelial cells was observed in the lumen

  19. Shedding of leukemia-associated P24 antigen by lymphoblastoid cell lines.

    Science.gov (United States)

    Komada, Y; Ochiai, H; Shimizu, K; Azuma, E; Kamiya, H; Sakurai, M

    1987-12-01

    We report the development of a unique enzyme-linked immunosorbent assay (ELISA) which makes possible the detection of leukemia-associated P24 antigen, utilizing its ability to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4 simultaneously. Using the RCA1/SJ-9A4-ELISA, P24 antigen, as few as 50 X 10(3) cells from a common acute lymphoblastic leukemia (C-ALL) cell line could be detected. The presence of D-galactose gave complete and specific inhibition of P24 antigen binding to RCA1. Matched concentrations of D-glucose and D-sucrose had no effect on binding. The release of the P24 antigen into the culture medium by a C-ALL cell line maintained at 37 degrees C could be detected; however, no P24 antigen was present in the culture medium when the cells were maintained at 4 degrees C. Sequential analysis of the culture medium for soluble P24 antigen revealed that release of the P24 antigen associated with cell growth. Molecular sieve chromatography of concentrated culture medium indicated that shed P24 antigen was eluted in the macromolecule fraction. P24 antigen was detected in the cerebrospinal fluid (CSF) of four patients with P24 positive ALL at the time of relapse of the central nervous system (CNS) and was undetectable while in complete remission. The CSF from three patients with P24 negative ALL and three patients with aseptic meningitis had no detectable activity.

  20. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation

  1. The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

    Science.gov (United States)

    Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard

    2018-05-01

    Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Thermohaline circulation: a missing equation and its climate-change implications

    Science.gov (United States)

    Ou, Hsien-Wang

    2018-01-01

    We formulate a box model of coupled ocean-atmosphere to examine the differential fields interactive with the thermohaline circulation (THC) and their response to global warming. We discern a robust convective bound on the atmospheric heat transport, which would divide the climate regime into warm and cold branches; but unlike the saline mode of previous box models, the cold state, if allowed, has the same-signed—though weaker—density contrast and THC as the present climate, which may explain its emergence from coupled general circulation models. We underscore the nondeterminacy of the THC due to random eddy shedding and apply the fluctuation theorem to constrain the shedding rate, thus closing the problem. The derivation reveals an ocean propelled toward the maximum entropy production (MEP) on millennial timescale (termed "MEP-adjustment"), the long timescale arising from the compounding effect of microscopic fluctuations in the shedding rate and their slight probability bias. Global warming may induce hysteresis between the two branches, like that seen in GCMs, but the cold transition is far more sensitive to the moistening than the heating effects as the latter would be countered by the hydrological feedback. The uni- or bi-modality of the current state—hence whether the THC may recover after the cold transition—depends on the global-mean convective flux and may not be easily assessed due to its observed uncertainty.

  3. Characterization of the neutralization determinants of equine arteritis virus using recombinant chimeric viruses and site-specific mutagenesis of an infectious cDNA clone

    International Nuclear Information System (INIS)

    Balasuriya, Udeni B.R.; Dobbe, Jessika C.; Heidner, Hans W.; Smalley, Victoria L.; Navarrette, Andrea; Snijder, Eric J.; MacLachlan, N. James

    2004-01-01

    We have used an infectious cDNA clone of equine arteritis virus (EAV) and reverse genetics technology to further characterize the neutralization determinants in the GP5 envelope glycoprotein of the virus. We generated a panel of 20 recombinant viruses, including 10 chimeric viruses that each contained the ORF5 (which encodes GP5) of different laboratory, field, and vaccine strains of EAV, a chimeric virus containing the N-terminal ectodomain of GP5 of a European strain of porcine reproductive and respiratory syndrome virus, and 9 mutant viruses with site-specific substitutions in their GP5 proteins. The neutralization phenotype of each recombinant chimeric/mutant strain of EAV was determined with EAV-specific monoclonal antibodies and EAV strain-specific polyclonal equine antisera and compared to that of their parental viruses from which the substituted ORF5 was derived. The data unequivocally confirm that the GP5 ectodomain contains critical determinants of EAV neutralization. Furthermore, individual neutralization sites are conformationally interactive, and the interaction of GP5 with the unglycosylated membrane protein M is likely critical to expression of individual epitopes in neutralizing conformation. Substitution of individual amino acids within the GP5 ectodomain usually resulted in differences in neutralization phenotype of the recombinant viruses, analogous to differences in the neutralization phenotype of field strains of EAV and variants generated during persistent infection of EAV carrier stallions

  4. Faecal bacterial composition in dairy cows shedding Mycobacterium avium subsp. paratuberculosis in faeces in comparison with nonshedding cows.

    Science.gov (United States)

    Kaevska, Marija; Videnska, Petra; Sedlar, Karel; Bartejsova, Iva; Kralova, Alena; Slana, Iva

    2016-06-01

    The aim of this study was to determine possible differences in the faecal microbiota of dairy cows infected with Mycobacterium avium subsp. paratuberculosis (Johne's disease) in comparison with noninfected cows from the same herds. Faecal samples from cows in 4 herds were tested for M. avium subsp. paratuberculosis by real-time PCR, and faecal bacterial populations were analysed by 454 pyrosequencing of the 16S rRNA gene. The most notable differences between shedding and nonshedding cows were an increase in the genus Psychrobacter and a decrease in the genera Oscillospira, Ruminococcus, and Bifidobacterium in cows infected with M. avium subsp. paratuberculosis. The present study is the first to report the faecal microbial composition in dairy cows infected with M. avium subsp. paratuberculosis.

  5. Sporocyst size of isolates of Sarcocystis shed by the Virginia opossum (Didelphis virginiana).

    Science.gov (United States)

    Cheadle, M A; Dame, J B; Greiner, E C

    2001-02-26

    The Virginia opossum (Didelphis virginiana) is a definitive host for multiple Sarcocystis species including Sarcocystis neurona, one of the causative agents of equine protozoal myeloencephalitis (EPM), a severe, neuromuscular disease of horses. Size and morphologic characteristics of isolates of Sarcocystis shed by the opossum were examined to determine if differences were useful in discriminating between the isolates and/or species. Collections of sporocysts from 17 opossums were molecularly characterized and measured using an ocular micrometer. The mean sporocyst size of isolates of S. neurona was 10.7 microm x 7.0 microm, Sarcocystis falcatula 11.0 microm x 7.1 microm, Sarcocystis speeri 12.2 microm x 8.8 microm, 1085-like isolate 10.9 microm x 6.8 microm, and 3344-like isolate 19.4 microm x 10.5 microm. The length and width of S. speeri were statistically different (p < 0.05) from the sporocysts of other types. The length of S. neurona and S. falcatula sporocysts were statistically different (p < 0.05) from each other and the width of S. falcatula and 1085 differed (p < 0.05). The fifth sporocyst type (3344) was observed, but due to pronounced morphological characteristics, statistical analysis was not performed. There was no consistent difference between the taxa based on internal structure of the sporocyst.

  6. Navigating the gender minefield: An IPV prevention campaign sheds light on the gender gap.

    Science.gov (United States)

    Keller, Sarah N; Honea, Joy C

    2016-01-01

    This article examines how differences in male and female views about intimate partner violence (IPV) contributed to divergent responses to a prevention campaign conducted in the western USA. The study examines focus groups (n = 22) and in-depth interview data (n = 13) collected during campaign development to shed light on quantitative results indicating that women (but not men) increased their perceived severity of domestic violence and awareness of services from pre-test to post-test, while male attitudes moved in the opposite direction. Results of the qualitative study provide the basis for the authors' conclusions about why reactions differed: (1) men's unwillingness to view abuse within a gender context limits men's ability to accept the inequity in statistically demonstrated male and female roles as perpetrators and victims; (2) male resentment of existing gender stereotypes contributed to a rejection of campaign messages that utilised gender prevalence statistics to depict images showing men as perpetrators and women as victims; and (3) victim blaming attitudes contributed to resistance to empathy for victims depicted in the campaign. The authors offer suggestions for future campaigns that foster agency among both perpetrators and survivors while confronting the structural barriers to enacting change.

  7. Summertime nocturnal drainage flow in the San Mateo and Ambrosia lake air sheds of the grants basin

    International Nuclear Information System (INIS)

    Gedayloo, T.; Barr, S.; Clements, W.E.; Wilson, S.K.

    1979-01-01

    An initial study of some fundamental meteorological properties of two major air sheds in the Grants Basin of northwestern New Mexico was conducted from May 18 to September 19, 1978. Three mechanical weather stations were used in conjunction with a few vertical wind soundings to develop a data set for the summer regime. Data collected between May 18 and July 30 is analyzed to investigate nocturnal drainage flows, daytime flows, and channeling of synoptic wind. Drainage wind averaging 2.5 m s -1 was found to exist in a surface layer not greater than 200 m deep on 60% of the nights investigated. This frequently occurring drainage flow is characterized by a strong decoupling from the upper level winds. Daytime winds, on the other hand, are representative of the synoptic flow patterns suggesting a rather rapid coupling after sunrise

  8. Design and optimization of the large span dry-coal-shed latticed shell in Liyuan of Henan province

    Directory of Open Access Journals (Sweden)

    Du Wenfeng

    2017-01-01

    Full Text Available The design and optimization about the large span dry-coal-shed latticed shell in Liyuan of Henan province were studied. On the basis of the structural scheme of double-layer cylindrical reticulated shell, the optimization scheme of the folding double-layer cylindrical reticulated shell was proposed. Through the analysis of a plurality of calculation models, the optimal geometric parameters were obtained after discussing the influence of different slopes of folding lines and shell thickness on the structural bearing capacity and the amount of steel. The research results show that in the case of the same amount of steel, the ultimate bearing capacity of the double-layer folding cylindrical reticulated shell whose folding line slope is 9% and the shell thickness is about 4.4m can be increased 27.3% compared with the original design scheme.

  9. PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

    Science.gov (United States)

    Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

    2015-04-01

    PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

  10. Main: MPA4 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available t for Alzheimer's disease Alzheimer's disease: γ-secretase Taisuke Tomita Graduate School of Pharmaceutical ...ing both the entire γ-secretase complex and the ectodomain of nicastrin - We have identified novel compounds

  11. An inactivated gE-deleted pseudorabies vaccine provides complete clinical protection and reduces virus shedding against challenge by a Chinese pseudorabies variant.

    Science.gov (United States)

    Wang, Jichun; Guo, Rongli; Qiao, Yongfeng; Xu, Mengwei; Wang, Zhisheng; Liu, Yamei; Gu, Yiqi; Liu, Chang; Hou, Jibo

    2016-12-07

    Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult. An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-A B ) strain. PRV(LA-A B ) strain can reach a titer of 10 8.43 TCID 50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-A B ) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-A B strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3-4 days) was shorter than in either the challenge control (5-10 days) or groups C and D (5-6 days). The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-A B )strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-A B provides clinical

  12. High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014

    Directory of Open Access Journals (Sweden)

    Elmoubasher A. B. A. Farag

    2015-07-01

    Full Text Available Two of the earliest Middle East respiratory syndrome (MERS cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105. Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.

  13. Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

    Science.gov (United States)

    Marriott, Anthony C; Dove, Brian K; Whittaker, Catherine J; Bruce, Christine; Ryan, Kathryn A; Bean, Thomas J; Rayner, Emma; Pearson, Geoff; Taylor, Irene; Dowall, Stuart; Plank, Jenna; Newman, Edmund; Barclay, Wendy S; Dimmock, Nigel J; Easton, Andrew J; Hallis, Bassam; Silman, Nigel J; Carroll, Miles W

    2014-01-01

    Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

  14. Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09 induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu and low (102 pfu doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

  15. Prevalence and characteristics of Shiga toxin-producing Escherichia coli in finishing pigs: Implications on public health.

    Science.gov (United States)

    Cha, Wonhee; Fratamico, Pina M; Ruth, Leah E; Bowman, Andrew S; Nolting, Jacqueline M; Manning, Shannon D; Funk, Julie A

    2018-01-02

    Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, which can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. To study the epidemiology of STEC in finishing pigs and examine the potential risks they pose for human STEC infections, we conducted a longitudinal cohort study in three finishing sites. Six cohorts of pigs (2 cohorts/site, 20 pigs/cohort) were randomly selected, and fecal samples (n=898) were collected every two weeks through their finishing period. Eighty-two pigs (68.3%) shed STEC at least once, and the proportion of STEC-positive pigs varied across sites (50-97.5%) and cohorts (15-100%). Clinically important serotypes, O157:H7 (stx 2c , eae) and O26:H11 (stx 1a , eae), were recovered from two pigs at sites C and A, respectively. The most common serotype isolated was O59:H21 (stx 2e ), which was particularly prevalent in site B as it was recovered from all STEC positive pigs (n=39). Each cohort showed different patterns of STEC shedding, which were associated with the prevalent serotype. The median shedding duration of STEC in pigs was 28days, consistent with our prior study. However, among pigs shedding O59:H21 at least once, pigs in cohort B2 had a significantly longer shedding duration of 42days (P<0.05) compared to other cohorts. Stx2e was the most commonly observed stx variant in finishing pigs (93.9%), in accordance with the previous studies. Stx2e has been reported to be significantly associated with edema disease in pigs, however, the pathogenicity in humans warrants further investigations. Nonetheless, our findings affirm that pigs are an important reservoir for human STEC infections, and that the circulating serotypes in a cohort and site management factors may significantly affect the prevalence of STEC. Molecular characterization of STEC isolates and epidemiological studies to identify risk factors for shedding in pigs are strongly warranted to further address the

  16. Porcine circovirus type 2 (PCV2) vaccination is effective in reducing disease and PCV2 shedding in semen of boars concurrently infected with PCV2 and Mycoplasma hyopneumoniae

    Science.gov (United States)

    The objectives of this study were to determine if the amount of porcine circovirus type 2 (PCV2) shed in semen will be increased in boars experimentally coinfected with Mycoplasma hyopneumoniae (MHYO) and if PCV2 vaccination of the boars prior to PCV2 exposure will result in reduced PCV2 viremia and...

  17. Flowering, nectar secretion, pollen shed and insect foraging on Aquilegia vulgaris L. (Ranunculaceae

    Directory of Open Access Journals (Sweden)

    Bożena Denisow

    2012-12-01

    Full Text Available This study on blooming biology, nectar secretion, pollen production and insect visitation of Aquilegia vulgaris L. was carried out in 2009 and 2011 in Lublin. The peak of flower opening during the day was between 5.00 and 7.00 (GMT +2. The flowers are protandrous with the female phase beginning approx. on the 3rd day of anthesis. The dynamics of nectar secretion and pollen shed from anthers (progressing from the central part of the androecium outwards support the reproductive system. The amount of nectar accumulated in the spurs increased from the bud stage and was the highest in the phase with approx. ¾ of dehisced anthers, usually on the 3rd day of flower life. Then, towards the end of anthesis, the amount of secreted and accumulated nectar decreased. The number of anthers developed per flower varied from 41 to 61 (mean = 49.1. The mass of pollen per 100 anthers averaged 6.7 mg. Pollen production per flower (mean = 3.28 mg slightly varied between years and was mainly correlated with the number of developed anthers. Estimated pollen yield was 1.69 g per m2 and sugar yield 1.22 g per m2. Species from the genus Bombus were the main flower visitors, with B. terrestris being the most frequent forager.

  18. Impact response of RC rock-shed girder with sand cushion under falling load

    International Nuclear Information System (INIS)

    Bhatti, Abdul Qadir; Kishi, Norimitsu

    2010-01-01

    Research highlights: → An applicability of FE model of RC girders with sand cushion has been investigated. → Experimental and numerical results of Impact force, reaction force and displacement have been performed. → Cracks obtained from numerical models are in good agreement with the experimental ones. → Reaction force-displacement loops agree well between numerical and experimental results. → The configuration of the hysteretic loop at failure of RC girders can be approximated by a parallelogram. - Abstract: In order to establish a proper finite element model of prototype RC girder with sand element for impact response analysis, dynamic response analysis of RC girders with sand cushion subjected to impact force due to weight falling from the height of H = 2.5, 5, 7.5 and 10 m was performed to improve the state of the art of protective design for real scale rock-sheds by using LS-DYNA code. An applicability of proposed model was discussed comparing with experimental results (e.g. impact force, reaction force and displacement waves). From this study, dynamic characteristics of impact response can be better simulated by using the proposed model. As a result, when the sand cushion was set up, the impact force, reaction force, mid-span displacement waves, distribution of reaction force-displacement loops, and crack patterns obtained from the numerical analysis are in good agreement with those from the experimental results.

  19. Power transfer capability assessment of transmission interfaces with SVC and load shedding systems

    Energy Technology Data Exchange (ETDEWEB)

    Pavlovsky, V. [DMCC-Engineering, Kiev (Ukraine). Inst. of Electrodynamics; Dolzhenitsa, Y. [DMCC Engineering, Kiev (Ukraine); Ushapovskiy, K. [National Power Co. Ukrenergo, Kiev (Ukraine)

    2009-07-01

    As a result of deregulation in the power industry, energy trade and markets are pushing transmission system operators to operate their systems closer to the edge of the power transfer capability. Voltage instability and inadequate reactive power support of generators is a key factor in most major outages around the world. The ideal way to control power systems is to avoid emergencies by reliable planning and secure operation of power systems. Therefore, the accurate calculation of the power transfer capability of transmission interfaces is an important task on the planning and operation stages. This paper discussed the issue of transfer capability assessment and monitoring for interfaces with static var compensator (SVC) and load shedding schemes. It also proposed a special measure, a distance to voltage instability point, to monitor transfer capability on-line. The distance may be observed by measurement of SVC output. The paper considered the problem of optimal SVC size selection and a new approach was proposed based on P-V curves analysis. The paper discussed the problem formulation and proposed approach. A case was also presented in order to demonstrate the proposed approach on the IPS Ukraine-Crimea interface. It was concluded that the proposed approach allows the optimal rating of SVC for increasing transfers capability of transmission corridors. 12 refs., 9 figs.

  20. How counterfactuals of Red-Queen theory shed light on science and its historiography.

    Science.gov (United States)

    Dagg, Joachim L

    2017-08-01

    A historical episode of evolutionary theory, which has lead to the Red Queen theory of the evolutionary maintenance of sex, includes two striking contingencies. These are used to explore alternative what-if scenarios, in order to test some common opinions about such counterfactuals. This sheds new light on the nature of science and its historiography. One counterfactual leads to an unexpected convergence of its result to that of the actual science but, nevertheless, differs in its causal structure. The other diverges towards an incompatible alternative, but this requires further contingent choices that also diverge from actual science. The convergence in the first counterfactual is due to a horizontal transfer of knowledge. Similar transfers of knowledge are typical for innovations of actual science. This suggests that contingent choices can merge as well as fork research traditions both in actual research and counterfactual history. Neither the paths of the actual history of science nor those of its counterfactual alternatives will form a tree of exclusively diverging bifurcations, but a network instead. Convergencies in counterfactuals may, therefore, be due to the web-structure of science as much as to the aims of the historians in question. Furthermore, the difference in causal structure between the actual science and its convergent counterfactual might become diagnostic for external factors rather than internal aims forcing a historian towards convergence. Copyright © 2017 Elsevier Ltd. All rights reserved.