77 research outputs found

    STAT2 Mediates Innate Immunity to Dengue Virus in the Absence of STAT1 via the Type I Interferon Receptor

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    Dengue virus (DENV) is a mosquito-borne flavivirus, and symptoms of infection range from asymptomatic to the severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). High viral loads correlate with disease severity, and both type I & II interferons (IFNs) are crucial for controlling viral replication. We have previously reported that signal transducer and activator of transcription (STAT) 1-deficient mice are resistant to DENV-induced disease, but little is known about this STAT1-independent mechanism of protection. To determine the molecular basis of the STAT1-independent pathway, mice lacking STAT1, STAT2, or both STAT1 and STAT2 were infected with a virulent mouse-adapted strain of DENV2. In the first 72 hours of infection, the single-deficient mice lacking STAT1 or STAT2 possessed 50–100 fold higher levels of viral RNA than wild type mice in the serum, spleen, and other visceral tissues, but remained resistant to DENV-induced death. In contrast, the double-deficient mice exhibited the early death phenotype previously observed in type I and II IFN receptor knockout mice (AG129), indicating that STAT2 is the mediator of the STAT1-independent host defense mechanism. Further studies demonstrated that this STAT2-dependent STAT1-independent mechanism requires the type I IFN receptor, and contributes to the autocrine amplification of type I IFN expression. Examination of gene expression in the spleen and bone marrow-derived macrophages following DENV infection revealed STAT2-dependent pathways can induce the transcription of a subset of interferon stimulated genes even in the absence of STAT1. Collectively, these results help elucidate the nature of the poorly understood STAT1-independent host defense mechanism against viruses by identifying a functional type I IFN/STAT2 signaling pathway following DENV infection in vivo

    Structuring effect of tools conceptualized through initial goal fixedness for work activity

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    Analysis of work activities in nuclear industry has highlighted a new psycho-cognitive phenomenon: the structuring effect of tools (SET) sometimes leading to unexpected operating deviations; the subject is unable to perform a task concerning object A using or adapting a tool designed and presented to perform the same task concerning object B when object A is expected by the subject. Conditions to isolate and identify the SET were determined and reproduced in experiments for further analysis. Students and seven professional categories of adults (N = 77) were involved in three experimental conditions (control group, group with prior warning, group with final control) while individually performing a task with similar characteristics compared to real operating conditions and under moderate time-pressure. The results were: (1) highest performance with prior warning and (2) demonstration that academic and professional training favor the SET. After discussing different cognitive processes potentially related to the SET, we described (3) the psycho-cognitive process underlying the SET: Initial Goal Fixedness (IGF), a combination of the anchoring of the initial goal of the activity with a focus on the features of the initial goal favored by an Einstellung effect. This suggested coping with the negative effect of the SET by impeding the IGF rather than trying to increase the subjects’ awareness at the expense of their health. Extensions to other high-risk industries were discussed

    Qualitative analysis of dependability argument structure

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    Mechanical and wear properties of palm oil fuel ash reinforced aluminum metal matrix composite

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    The metal matrix composites consist of unique properties that make the materials become more attractive in a variety of industrial applications. Palm oil fuel ash (POFA) is produced from the burning of palm oil shell and husk fiber in generation plant boiler for energy generation that serve the palm oil extraction purposes. It has been discarded as agricultural industrial wastes. However, POFA contains a high percentage of hard silica (SiO2) which therefore makes it extremely valuable for manufacturing high strength composites materials including electronic, ceramic, polymer, glass, and construction materials industries. In this paper, it evaluated the use of Palm Oil Fuel Ash (POFA) particles in the production of Al-MMC in order to strengthen the properties of the base metal. Particle-size of 75 and different volume fraction of Palm Oil Fuel Ash (POFA) particles (5%, 10% and 15%) particulate-reinforced Al-MMCs are fabricated by using the stir casting method and tested for mechanical properties. The microstructure of the fabricated composite material are also studied and analyzed in this study. It was observed that the tensile and impact strength and wear resistance of the composite increased substantially as the volume fraction of reinforcing particle increased

    Bio-ethanol production from Jatropha curcus

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    Demonstration of safety in healthcare organisations

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