196 research outputs found

    Calculation of secondary-electron escape currents from inclined-spacecraft surfaces in a magnetic field

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    In low Earth orbit, the geomagnetic field B(vector) is strong enough that secondary electrons emitted from spacecraft surfaces have an average gyroradius much smaller than typical dimensions of large spacecraft. This implies that escape of secondaries will be strongly inhibited on surfaces which are nearly parallel to B(vector), even if a repelling electric field exists outside them. This effect is likely to make an important contribution to the current balance and hence the equilibrium potential of such surfaces, making high voltage charging of them more likely. Numerically calculated escaping secondary electron fluxes are presented for these conditions. For use in numerical spacecraft charging simulations, an analytic curve fit to these results is given which is accurate to within 3% of the emitted current

    Numerical simulation of spacecraft charging phenomena

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    A numerical simulation program is being constructed having the following features: (1) infinite circular cylindrical geometry with angle-dependence, (2) inclusion of incident particles, photoelectrons, secondary electrons, backscattered electrons, any gun emissions, and any internal current pathways including surface conductive layers, (3) quasistatic time-dependent iteration, in which sheath potential changes during particle transit times are ignored, (4) use of approximate, locally-dependent space charge density expressions in solving Poisson's equation for sheath potentials, with use of numerical orbit-following to determine surface currents, and (5) incident particle velocity distributions isotropic or beam-like, or some superposition of these. Rationales for each of these features are discussed

    Current collection in a magnetoplasma

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    The authors present a survey of a very incomplete subject, current collection in a magnetoplasma. The best-developed and simplest theories for current collection are steady-state collisionless theories, and these must be understood before departures from them can be analyzed usefully. Thus, the authors begin with a review of them. The authors include some recent numerical results which indicate that steady-state collisionless Laplace-limit currents remain substantially below the Parker-Murphy (1967) canonical upper bound out to very large electrode potentials, and approach it as a limit only very slowly if at all. Attempts to correct this theory for space-charge effects lead to potential disturbances which extend to infinite distance along the electrode's magnetic shadow, unless collisional effects are also taken into account. However, even a small amount of relative plasma drift motion, such as that involved in a typical rocket experiment, can change this conclusion fundamentally. It is widely believed that time-averaged current collection may be increased by effects of plasma turbulence, and the authors review the available evidence for and against this contention. Steady-state collisionless particle dynamics predicts the existence of a toroidal region of trapped orbits which surrounds the electrode. Light emissions from this region have been photographed, indicating that collisional ionization may also occur there, and this, and/or scattering by collisions or possibly turbulent fluctuations in this region, may also increase current collection by the electrode. The authors also discuss effects on particle motions near the electrode, associated with breakdown of magnetic insulation in the region of large electric fields near it

    Prediction of large negative shaded-side spacecraft potentials

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    A calculation by Knott, for the floating potential of a spherically symmetric synchronous-altitude satellite in eclipse, was adapted to provide simple calculations of upper bounds on negative potentials which may be achieved by electrically isolated shaded surfaces on spacecraft in sunlight. Large (approximately 60 percent) increases in predicted negative shaded-side potentials are obtained. To investigate effective potential barrier or angular momentum selection effects due to the presence of less negative sunlit-side or adjacent surface potentials, these expressions were replaced by the ion random current, which is a lower bound for convex surfaces when such effects become very severe. Further large increases in predicted negative potentials were obtained, amounting to a doubling in some cases

    Experimental and computational characterization of a modified GEC cell for dusty plasma experiments

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    A self-consistent fluid model developed for simulations of micro- gravity dusty plasma experiments has for the first time been used to model asymmetric dusty plasma experiments in a modified GEC reference cell with gravity. The numerical results are directly compared with experimental data and the experimentally determined dependence of global discharge parameters on the applied driving potential and neutral gas pressure is found to be well matched by the model. The local profiles important for dust particle transport are studied and compared with experimentally determined profiles. The radial forces in the midplane are presented for the different discharge settings. The differences between the results obtained in the modified GEC cell and the results first reported for the original GEC reference cell are pointed out

    Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPR(mt) to promote metastasis

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    By causing mitochondrial DNA (mtDNA) mutations and oxidation of mitochondrial proteins, reactive oxygen species (ROS) leads to perturbations in mitochondrial proteostasis. Several studies have linked mtDNA mutations to metastasis of cancer cells but the nature of the mtDNA species involved remains unclear. Our data suggests that no common mtDNA mutation identifies metastatic cells; rather the metastatic potential of several ROS-generating mutations is largely determined by their mtDNA genomic landscapes, which can act either as an enhancer or repressor of metastasis. However, mtDNA landscapes of all metastatic cells are characterized by activation of the SIRT/FOXO/SOD2 axis of the mitochondrial unfolded protein response (UPR(mt)). The UPR(mt) promotes a complex transcription program ultimately increasing mitochondrial integrity and fitness in response to oxidative proteotoxic stress. Using SOD2 as a surrogate marker of the UPR(mt), we found that in primary breast cancers, SOD2 is significantly increased in metastatic lesions. We propose that the ability of selected mtDNA species to activate the UPR(mt) is a process that is exploited by cancer cells to maintain mitochondrial fitness and facilitate metastasis.Oncogene advance online publication, 3 April 2017; doi:10.1038/onc.2017.52

    Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

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    While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

    Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus

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    We report a biomarker-based non-endoscopic method for detecting Barrett’s esophagus (BE), based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma (EAC). Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve (AUC)=0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals, who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 minutes. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE

    TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays

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    <p>Abstract</p> <p>Background</p> <p>High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH) analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses.</p> <p>Results</p> <p>We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances.</p> <p>Conclusions</p> <p>TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH) in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific) CRMA v2 for Affymetrix or BeadStudio's (proprietary) XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package <it>aroma.cn</it>, which is part of the Aroma Project (<url>http://www.aroma-project.org/</url>).</p
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