1,298 research outputs found

    Modeling of the effect of a thermoelectric magnetic force onto conducting particles immersed in the liquid metal

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    International audienceSimulation of a thermo-electromagnetic force which acts on a conducting particle immersed into liquid metal is performed using multi-gird multi-physics software AEQUATIO. To verify numerical solutions a model thermoelectric problem is solved using two methods. In the first one a phase function is used to indicate the phase transition whereas in the second the solid particle is described with a real frontier of a simplified shape. Numerical and analytical solutions for a model problem qualitatively agree but strong oscillations are observed in a numerical solution with a phase function. Further AEQUQTIO is applied for calculation of the velocity of a dendrite fragment observed in-situ in experiment of solidification of AlCu alloy. Numerical solution gives a good agreement with the experimental observation

    Probing the dynamics of quasicrystal growth using synchrotron live imaging

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    The dynamics of quasicrystal growth remains an unsolved problem in condensed matter. By means of synchrotron live imaging, facetted growth proceeding by the tangential motion of ledges at the solid-melt interface is clearly evidenced all along the solidification of icosahedral AlPdMn quasicrystals. The effect of interface kinetics is significant so that nucleation and free growth of new facetted grains occur in the melt when the solidification rate is increased. The evolution of these grains is explained in details, which reveals the crucial role of aluminum rejection, both in the poisoning of grain growth and driving fluid flow

    The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen

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    The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a pandemic outbreak. Most notable of these viral strains are the H5N1 highly pathogenic AI and the H7N9 low pathogenicity AI viruses, both of which have mortality rates above 30%. Understanding of their mechanisms of infection and pathobiology is key to our preparation for these and future viral strains of high consequence. AI viruses typically circulate in wild bird populations, commonly infecting waterfowl and also regularly entering commercial poultry flocks. Live poultry markets provide an ideal environment for the spread AI and potentially the selection of mutants with a greater propensity for infecting humans because of the potential for spill over from birds to humans. Pathology from these AI virus infections is associated with a dysregulated immune response, which is characterized by systemic spread of the virus, lymphopenia, and hypercytokinemia. It has been well documented that host/pathogen interactions, particularly molecules of the immune system, play a significant role in both disease susceptibility as well as disease outcome. Here, we review the immune/virus interactions in both avian and mammalian species, and provide an overview or our understanding of how immune dysregulation is driven. Understanding these susceptibility factors is critical for the development of new vaccines and therapeutics to combat the next pandemic influenza

    HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells

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    Seasonal influenza virus infections cause 290,000–650,000 deaths annually and severe morbidity in 3–5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαÎČ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαÎČ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases

    Farm-Level Risk Factors for Fish-Borne Zoonotic Trematode Infection in Integrated Small-Scale Fish Farms in Northern Vietnam

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    BACKGROUND: Northern Vietnam is an endemic region for fish-borne zoonotic trematodes (FZT), including liver and intestinal flukes. Humans acquire the FZT infection by eating raw or inadequately cooked fish. The production of FZT-free fish in aquaculture is a key component in establishing a sustainable program to prevent and control the FZT transmission to humans. Interventions in aquaculture should be based on knowledge of the main risk factors associated with FZT transmission. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal study was carried out from June 2006 to May 2007 in Nam Dinh province, Red River Delta to investigate the development and risk factors of FZT infections in freshwater cultured fish. A total of 3820 fish were sampled six times at two-month intervals from 96 fish farms. Logistic analysis with repeated measurements was used to evaluate potential risk factors based on information collected through questionnaire interviews with 61 fish farm owners. The results showed that the FZT infections significantly increased from first sampling in June to July 2006 (65%) to sixth sampling in April to May, 2007 (76%). The liver fluke, Clonorchis sinensis and different zoonotic intestinal flukes including Haplochis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus and Procerovum varium were found in sampled fish. Duration of fish cultured (sampling times), mebendazole drug self-medication of household members, presence of snails in the pond, and feeding fish with green vegetation collected outside fish farms all had a significant effect on the development of FZT prevalence in the fish. CONCLUSIONS/SIGNIFICANCE: The FZT prevalence in fish increased by 11 percentage points during a one-year culture period and the risk factors for the development of infection were identified. Results also highlight that the young fish are already highly infected when stocked into the grow-out systems. This knowledge should be incorporated into control programs of FZT transmission in integrated small-scale aquaculture nursery and grow-out systems in Vietnam

    A serological assay to detect SARS-CoV-2 seroconversion in humans

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    Development of an enzyme-linked immunosorbent assay to detect antibodies to the SARS-CoV-2 spike protein in human sera and plasma. Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.Peer reviewe

    Butyrate Transcriptionally Enhances Peptide Transporter PepT1 Expression and Activity

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    Background: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. Results: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1) promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by,2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles

    Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

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    Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius AA. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio
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