41 research outputs found

    LDEF Space Plasma-High Voltage Drainage Experiment post-flight results

    Get PDF
    The Space Plasma-High Voltage Drainage Experiment (SP-HVDE) was comprised of two identical experimental trays. With one tray located on the leading (ram facing, B10) edge and the other located on the trailing (wake facing, D4) edge of the Long Duration Exposure Facility (LDEF), it was possible to directly compare the effects of ram and wake spacecraft environments on charged dielectric materials. Six arrays of Kapton dielectric samples of 2 mil, 3 mil, and 5 mil thicknesses maintained at +/- 300, +/- 500, and +/- 1000 voltage bias formed the experimental matrix of each tray. In addition, each tray carried two solar cell strings, one biased at +300 volts and the other at -300 volts, to study current leakage from High Voltage Solar Arrays (HVSA). The SP-HVDE provides the first direct, long-term, in-flight measurements of average leakage current through dielectric materials under electric stress. The experiment also yields information on the long term stability of the bulk dielectric properties of such materials. Data and findings of the SP-HVDE are an extension of those from shorter term flight experiments such as the PIX-1 (Plasma Interaction Experiment) and PIX-2 and are therefore valuable in the design and evaluation of long-lived space systems with high voltage systems exposed to the low earth orbital environment. A summary of the SP-HVDE post flight analysis final report delivered to the LDEF Project Office under contract to the National Aeronautics and Space Administration is presented

    Autologous non-myeloablative hematopoietic stem cell transplantation for diffuse scleroderma

    Get PDF

    αB Crystallin Is Apically Secreted within Exosomes by Polarized Human Retinal Pigment Epithelium and Provides Neuroprotection to Adjacent Cells

    Get PDF
    αB Crystallin is a chaperone protein with anti-apoptotic and anti-inflammatory functions and has been identified as a biomarker in age-related macular degeneration. The purpose of this study was to determine whether αB crystallin is secreted from retinal pigment epithelial (RPE) cells, the mechanism of this secretory pathway and to determine whether extracellular αB crystallin can be taken up by adjacent retinal cells and provide protection from oxidant stress. We used human RPE cells to establish that αB crystallin is secreted by a non-classical pathway that involves exosomes. Evidence for the release of exosomes by RPE and localization of αB crystallin within the exosomes was achieved by immunoblot, immunofluorescence, and electron microscopic analyses. Inhibition of lipid rafts or exosomes significantly reduced αB crystallin secretion, while inhibitors of classic secretory pathways had no effect. In highly polarized RPE monolayers, αB crystallin was selectively secreted towards the apical, photoreceptor-facing side. In support, confocal microscopy established that αB crystallin was localized predominantly in the apical compartment of RPE monolayers, where it co-localized in part with exosomal marker CD63. Severe oxidative stress resulted in barrier breakdown and release of αB crystallin to the basolateral side. In normal mouse retinal sections, αB crystallin was identified in the interphotoreceptor matrix. An increased uptake of exogenous αB crystallin and protection from apoptosis by inhibition of caspase 3 and PARP activation were observed in stressed RPE cultures. αB Crystallin was taken up by photoreceptors in mouse retinal explants exposed to oxidative stress. These results demonstrate an important role for αB crystallin in maintaining and facilitating a neuroprotective outer retinal environment and may also explain the accumulation of αB crystallin in extracellular sub-RPE deposits in the stressed microenvironment in age-related macular degeneration. Thus evidence from our studies supports a neuroprotective role for αB crystallin in ocular diseases

    Mechanism of RPE Cell Death in α-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux

    Get PDF
    Absence of α-crystallins (αA and αB) in retinal pigment epithelial (RPE) cells renders them susceptible to oxidant-induced cell death. We tested the hypothesis that the protective effect of α-crystallin is mediated by changes in cellular glutathione (GSH) and elucidated the mechanism of GSH efflux. In α-crystallin overexpressing cells resistant to cell death, cellular GSH was >2 fold higher than vector control cells and this increase was seen particularly in mitochondria. The high GSH levels associated with α-crystallin overexpression were due to increased GSH biosynthesis. On the other hand, cellular GSH was decreased by 50% in murine retina lacking αA or αB crystallin. Multiple multidrug resistance protein (MRP) family isoforms were expressed in RPE, among which MRP1 was the most abundant. MRP1 was localized to the plasma membrane and inhibition of MRP1 markedly decreased GSH efflux. MRP1-suppressed cells were resistant to cell death and contained elevated intracellular GSH and GSSG. Increased GSH in MRP1-supressed cells resulted from a higher conversion of GSSG to GSH by glutathione reductase. In contrast, GSH efflux was significantly higher in MRP1 overexpressing RPE cells which also contained lower levels of cellular GSH and GSSG. Oxidative stress further increased GSH efflux with a decrease in cellular GSH and rendered cells apoptosis-prone. In conclusion, our data reveal for the first time that 1) MRP1 mediates GSH and GSSG efflux in RPE cells; 2) MRP1 inhibition renders RPE cells resistant to oxidative stress-induced cell death while MRP1 overexpression makes them susceptible and 3) the antiapoptotic function of α-crystallin in oxidatively stressed cells is mediated in part by GSH and MRP1. Our findings suggest that MRP1 and α crystallin are potential therapeutic targets in pathological retinal degenerative disorders linked to oxidative stress

    The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation

    Get PDF

    A back-illuminated 3D-stacked single-photon avalanche diode in 45nm CMOS technology, 2017 IEEE International Electron Devices Meeting (IEDM)

    No full text
    We report on the world's first back-illuminated 3D-stacked single-photon avalanche diode (SPAD) in 45nm CMOS technology. This SPAD achieves a dark count rate of 55.4cps/ÎĽm 2 , a maximum photon detection probability of 31.8% at 600nm, over 5% in the 420-920nm wavelength range, and timing jitter of 107.7ps at 2.5V excess bias voltage and room temperature. To the best of our knowledge, these are the best results ever reported for any back-illuminated 3D-stacked SPAD technology
    corecore