85 research outputs found

    The Development of Stacked Core for the Fabrication of Deep Lightweight UV-Quality Space Mirrors

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    The 2010 Decadal Survey stated that an advanced large-aperture ultraviolet, optical, near-infrared (UVOIR) telescope is required to enable the next generation of compelling astrophysics and exoplanet science; and, that present technology is not mature enough to affordably build and launch any potential UVOIR mission concept. Under Science and Technology funding, NASA's Marshall Space Flight Center (MSFC) and Exelis have developed a more cost effective process to make 4m class or larger monolithic spaceflight UV quality, low areal density, thermally and dynamically stable primary mirrors. A proof of concept 0.43m mirror was completed at Exelis optically tested at 250K at MSFC which demonstrated the ability for imaging out to 2.5 microns. The parameters and test results of this concept mirror are shown. The next phase of the program includes a 1.5m subscale mirror that will be optically and dynamically tested. The scale-up process will be discussed and the technology development path to a 4m mirror system by 2018 will be outlined

    Status of the Advanced Mirror Technology Development (AMTD) Phase 2, 1.5m ULE(Registered Trademark) Mirror

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    The Decadal Survey stated that an advanced large-aperture ultraviolet, optical, near-infrared (UVOIR) telescope is required to enable the next generation of compelling astrophysics and exoplanet science; and, that present technology is not mature enough to affordably build and launch any potential UVOIR mission concept. Under Science and Technology funding, NASA's Marshall Space Flight Center (MSFC) and Exelis have developed a more cost effective process to make up to 4m monolithic spaceflight UV quality, low areal density, thermally and dynamically stable primary mirrors. Under a Phase I program, a proof of concept mirror was completed at Exelis and tested down to 250K at MSFC which would allow imaging out to 2.5 microns. In 2014, Exelis and NASA started a Phase II program to design and build a 1.5m mirror to demonstrate lateral scalability to a 4m monolithic primary mirror. The current status of the Phase II development program will be provided along with a Phase II program summary

    Removing Orbital Debris with Lasers

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    Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

    Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy

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    It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000 CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive to acute exercise demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/memory

    Wide Field Infrared Survey Telescope (WFIRST) Observatory Overview

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    NASA's Wide Field Infrared Survey Telescope (WFIRST) is being designed to deliver unprecedented capability in dark energy and exoplanet science, and to host a technology demonstration coronagraph for exoplanet imaging and spectroscopy. The observatory design has matured since 2013; we present a comprehensive description of the observatory configuration as refined during the WFIRST Phase-A study. The observatory is based on an existing, repurposed 2.4 meter space telescope coupled with a 288 megapixel near-infrared (0.6 to 2 microns) HgCdTe focal plane array with multiple imaging and spectrographic modes. Together they deliver a 0.28 square degree field of view, which is approximately 100 times larger than the Hubble Space Telescope, and a sensitivity that enables rapid science surveys. In addition, the coronagraph technology demonstration will prove the feasibility of new techniques for exoplanet discovery, imaging, and spectral analysis. A composite truss structure meters both instruments to the telescope assembly, and the instruments and the spacecraft are flight serviceable. We present configuration changes since 2013 that improved interfaces, improved testability, and reduced technical risk. We provide an overview of our Integrated Modeling results, performed at an unprecedented level for a phase-A study, to illustrate performance margins with respect to static wavefront error, jitter, and thermal drift

    Widespread modulation of gene expression by copy number variation in skeletal muscle

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    Copy number variation (CNV) is a frequently observed deviation from the diploid state due to duplication or deletion of genomic regions. Although intensively analyzed for association with diseases and production traits, the specific mechanisms and extent by which such variations affect the phenotype are incompletely understood. We present an integrative study on CNV and genome-wide gene expression in Brazilian Bos indicus cattle. We analyzed CNVs inferred from SNP-chip data for effects on gene expression measured with RNA-seq in skeletal muscle samples of 183 steers. Local effects, where expression changes coincided with CNVs in the respective genes, were restricted to immune genes. Distal effects were attributable to several high-impact CNVs that modulated remote expression in an orchestrated and intertwined fashion. These CNVs were located in the vicinity of major skeletal muscle pathway regulators and associated genes were enriched for proteolysis, autophagy, and muscle structure development. From association analysis between CNVs and several meat quality and production traits, we found CNV-associated expression effects to also manifest at the phenotype level. Based on genome sequences of the population founders, we further demonstrate that CNVs with impact on expression and phenotype are passed on from one generation to another

    Plasticity of the Muscle Stem Cell Microenvironment

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    Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes

    The HELLP syndrome: Clinical issues and management. A Review

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    <p>Abstract</p> <p>Background</p> <p>The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence.</p> <p>Methods</p> <p>Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases.</p> <p>Results and conclusion</p> <p>About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·10<sup>9</sup>/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.</p

    Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation

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    © 2016 The Author(s) Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation. Cell death under these conditions was associated with increased caspase activity, suppression of differentiation, reductions in both creatine kinase activity and gene expression of myogenic factors; IGF-II, IGFBP-5, MyoD and myogenin. However, inhibition of caspase activity via administration of Z-VDVAD-FMK (caspase-2), Z-DEVD-FMK (caspase-3) and ZIETD-KMK (caspase 8) was without effect on cell death. By contrast, lipotoxicity associated with elevated palmitate was reduced with the MEK inhibitor PD98059, indicating palmitate induced cell death was MAPK mediated. These lipotoxic conditions were further exacerbated in the presence of inflammation via TNF-α co-administration. Addition of EPA under cytotoxic stress (TNF-α) was shown to partially rescue differentiation with enhanced myotube formation being associated with increased MyoD, myogenin, IGF-II and IGFBP-5 expression. EPA had little impact on the cell death phenotype observed in lipotoxic conditions but did show benefit in restoring differentiation under lipotoxic plus cytotoxic conditions. Under these conditions Id3 (inhibitor of differentiation) gene expression was inversely linked with survival rates, potentially indicating a novel role of EPA and Id3 in the regulation of apoptosis in lipotoxic/cytotoxic conditions. Additionally, signalling studies indicated the combination of lipo- and cyto-toxic effects on the muscle cells acted through ceramide, JNK and MAPK pathways and blocking these pathways using PD98059 (MEK inhibitor) and Fumonisin B1 (ceramide inhibitor) significantly reduced levels of cell death. These findings highlight novel pathways associated with in vitro models of lipotoxicity (palmitate-mediated) and cytotoxicity (inflammatory cytokine mediated) in the potential targeting of molecular modulators of sarcopenic obesity
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