226 research outputs found

    Increased immunoglobulin response to [gamma]-interferon by lymphocytes from patients with systemic lupus erythematosus

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    The factors responsible for abnormal B-cell activation in systemic lupus erythematosus (SLE) are incompletely understood. This study tested the hypothesis that the abnormal B-cell activation observed in human SLE may be due to an augmented response to a helper signal. We demonstrated that non-T cells from 10 of 19 SLE patients increased IgG production in response to interferon-[gamma] (IFN-[gamma]) by a mean factor of 20.9 +/- 3.9 over resting levels, while controls stimulated a mean factor of 3.0 +/- 0.5 (P < 0.005). We found no relationship of IFN-[gamma] responsiveness to disease activity. Serotyping for HLA A, B, C, and D loci suggested that the hyperresponsiveness may be genetically linked to HLA-Cw7. We conclude that IFN-[gamma] may contribute to the development and perpetuation of SLE in a subset of patients with SLE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27486/1/0000529.pd

    Increased Oxygen Recovery from Sabatier Systems Using Plasma Pyrolysis Technology and Metal Hydride Separation

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    State-of-the-art life support carbon dioxide (CO2) reduction technology is based on the Sabatier reaction where less than 50% of the oxygen required for the crew is recovered from metabolic CO2. The reaction produces water as the primary product and methane as a byproduct. Oxygen recovery is constrained by the limited availability of reactant hydrogen. This is further exacerbated when Sabatier methane (CH4) is vented as a waste product resulting in a continuous loss of reactant hydrogen. Post-processing methane with the Plasma Pyrolysis Assembly (PPA) to recover hydrogen has the potential to dramatically increase oxygen recovery and thus drastically reduce the logistical challenges associated with oxygen resupply. The PPA decomposes methane into predominantly hydrogen and acetylene. Due to the highly unstable nature of acetylene, a separation system is necessary to purify hydrogen before it is recycled back to the Sabatier reactor. Testing and evaluation of a full-scale Third Generation PPA is reported and investigations into metal hydride hydrogen separation technology is discussed

    Crack-Like Processes Governing the Onset of Frictional Slip

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    We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

    Functional Performance of an Enabling Atmosphere Revitalization Subsystem Architecture for Deep Space Exploration Missions

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    A subsystem architecture derived from the International Space Station's (ISS) Atmosphere Revitalization Subsystem (ARS) has been functionally demonstrated. This ISS-derived architecture features re-arranged unit operations for trace contaminant control and carbon dioxide removal functions, a methane purification component as a precursor to enhance resource recovery over ISS capability, operational modifications to a water electrolysis-based oxygen generation assembly, and an alternative major atmospheric constituent monitoring concept. Results from this functional demonstration are summarized and compared to the performance observed during ground-based testing conducted on an ISS-like subsystem architecture. Considerations for further subsystem architecture and process technology development are discussed

    Evaluation of an Atmosphere Revitalization Subsystem for Deep Space Exploration Missions

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    An Atmosphere Revitalization Subsystem (ARS) suitable for deployment aboard deep space exploration mission vehicles has been developed and functionally demonstrated. This modified ARS process design architecture was derived from the International Space Station's (ISS) basic ARS. Primary functions considered in the architecture include trace contaminant control, carbon dioxide removal, carbon dioxide reduction, and oxygen generation. Candidate environmental monitoring instruments were also evaluated. The process architecture rearranges unit operations and employs equipment operational changes to reduce mass, simplify, and improve the functional performance for trace contaminant control, carbon dioxide removal, and oxygen generation. Results from integrated functional demonstration are summarized and compared to the performance observed during previous testing conducted on an ISS-like subsystem architecture and a similarly evolved process architecture. Considerations for further subsystem architecture and process technology development are discussed

    Apelin Is Required for Non-Neovascular Remodeling in the Retina

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    Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up-regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non-neovascular remodeling

    Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad

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    BACKGROUND: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. RESULTS: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. CONCLUSIONS: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.The MenAfriCar consortium, funded by the Wellcome Trust (grant number: 086546/Z/08/Z) and the Bill and Melinda Gates Foundation (grant number: 51251) supported the costs of sequencing. Kanny Diallo holds a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine (grant number: 103957/Z/14/Z). The funding sources had no role in the study design, collection, analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication. Martin Maiden was supported by the Wellcome Trust (grant number: 087622/Z/08/Z)
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