184 research outputs found

    NLS cycle 1 and NLS 2 base heating technical notes. Appendix 3: Preliminary cycle 1 NLS base heating environments. Cycle 1 NLS base heating environments. NLS 2 650K STME base heating environments

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    A preliminary analysis of National Launch System ascent plume induced base heating environments has been completed to support the Induced Environments Panel's objective to assist in maturing the NLS vehicle (1.5 stage and heavy launch lift vehicle) design. Environments during ascent have been determined from this analysis for a few selected locations on the engine nozzles and base heat shield for both vehicles. The environments reflect early summer 1991 configurations and performance data and conservative methodology. A more complete and thorough analysis is under way to update these environments for the cycle 1 review in January 1992

    Quasi-single helicity spectra in the Madison Symmetric Torus

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    Evidence of a self-organized collapse towards a narrow spectrum of magnetic instabilities in the Madison Symmetric Torus [R. N. Dexter, D. W. Kerst, T. W. Lovell, S. C. Prager, and J. C. Sprott, Fusion Technol. 19, 131 (1991)] reversed field pinch device is presented. In this collapsed state, dubbed quasi-single helicity (QSH), the spectrum of magnetic modes condenses spontaneously to one dominant mode more completely than ever before observed. The amplitudes of all but the largest of the m=1 modes decrease in QSH states. New results about thermal features of QSH spectra and the identification of global control parameters for their onset are also discussed

    Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection.

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    BACKGROUND: Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. METHODS: To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5-12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or alphaPD1 ligand were studied. RESULTS: Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation. CONCLUSION: In outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts

    Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

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    We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8(+) T cell-eliciting epitopes, a universal CD4(+) helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8(+) T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8(+) T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis

    An Empirical Strategy for Characterizing Bacterial Proteomes across Species in the Absence of Genomic Sequences

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    Global protein identification through current proteomics methods typically depends on the availability of sequenced genomes. In spite of increasingly high throughput sequencing technologies, this information is not available for every microorganism and rarely available for entire microbial communities. Nevertheless, the protein-level homology that exists between related bacteria makes it possible to extract biological information from the proteome of an organism or microbial community by using the genomic sequences of a near neighbor organism. Here, we demonstrate a trans-organism search strategy for determining the extent to which near-neighbor genome sequences can be applied to identify proteins in unsequenced environmental isolates. In proof of concept testing, we found that within a CLUSTAL W distance of 0.089, near-neighbor genomes successfully identified a high percentage of proteins within an organism. Application of this strategy to characterize environmental bacterial isolates lacking sequenced genomes, but having 16S rDNA sequence similarity to Shewanella resulted in the identification of 300–500 proteins in each strain. The majority of identified pathways mapped to core processes, as well as to processes unique to the Shewanellae, in particular to the presence of c-type cytochromes. Examples of core functional categories include energy metabolism, protein and nucleotide synthesis and cofactor biosynthesis, allowing classification of bacteria by observation of conserved processes. Additionally, within these core functionalities, we observed proteins involved in the alternative lactate utilization pathway, recently described in Shewanella

    Defining the Middle Corona

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    International audienceAbstract The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there
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