1,013 research outputs found

    Applying Response Surface Methodology to Readiness-Based Leveling of Reparable Items

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    Reparable items play a large role in determining the readiness of United States Air Force weapon systems. Many factors characterizing flying tempo and item repair and transit time influence the level of fleet readiness. Readiness-Based Leveling (RBL) considers these factors as it seeks to maximize aircraft readiness as it allocates spare reparable items between bases and a depot. The purpose of this research was to demonstrate the validity of using response surface methodology (RSM) within the context of RBL in an effort to quantify the influences these factors have on aircraft readiness. RSM applied designed experiments and least squares regressions in developing a series of empirical models quantifying correlations between one uncontrollable and seven controllable factors and RBL\u27s output. Verification tests indicated the empirical models represented -- to a high degree -- the quantitative relationships present between the inputs and output of RBL. Although valid conclusions cannot be made from the models (a substitute input was used in place of a usual D041 input), the methodology as demonstrated is valid

    Derivation of the Exponential Distribution through an Infinite Sine Series

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    This communication provides a derivation of the often-used oneparameter exponential family of distributions based on an infinite sine series. The main results associated with this derivation are the finite approximations of the probability density function (pdf) and the cumulative distribution function (cdf) of the exact one-parameter exponential family of distributions. The limit of these finite functions are the exact pdf and cdf. Numerical examples are provided to compare and contrast the finite approximations of distributions in terms of error using the finite-based cdf and the exact standard exponential cdf. We would also note that the finite approximations of the pdf and cdf vary in terms of both shape and percentage points. In view of this, the finite pdf and cdf offer a user the flexibility to potentially provide more accurate approximations in the context of fitting distributions to data rather than approximations that are based solely on the exact exponential pdf or cdf – most notably when distributions are heavy-(right)tailed

    NASA's Space Launch System Progress Report

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    Exploration beyond Earth orbit will be an enduring legacy for future generations, as it provides a platform for science and exploration that will define new knowledge and redefine known boundaries. NASA s Space Launch System (SLS) Program, managed at the Marshall Space Flight Center, is responsible for designing and developing the first exploration-class rocket since the Apollo Program s Saturn V that sent Americans to the Moon in the 1960s and 1970s. The SLS offers a flexible design that may be configured for the Orion Multi-Purpose Crew Vehicle with associated life-support equipment and provisions for long journeys or may be outfitted with a payload fairing that will accommodate flagship science instruments and a variety of high-priority experiments. Building on legacy systems, facilities, and expertise, the SLS will have an initial lift capability of 70 tonnes (t) in 2017 and will be evolvable to 130 t after 2021. While commercial launch vehicle providers service the International Space Station market, this capability will surpass all vehicles, past and present, providing the means to do entirely new missions, such as human exploration of Mars. Building on the foundation laid by over 50 years of human and scientific space flight and on the lessons learned from the Apollo, Space Shuttle, and Constellation Programs the SLS team is delivering both technical trade studies and business case analyses to ensure that the SLS architecture will be safe, affordable, reliable, and sustainable. This panel will address the planning and progress being made by NASA s SLS Program

    Overview of the Development and Mission Application of the Advanced Electric Propulsion System (AEPS)

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    NASA remains committed to the development and demonstration of a high-power solar electric propulsion capability for the Agency. NASA is continuing to develop the 14 kilowatt Advanced Electric Propulsion System (AEPS), which has recently completed an Early Integrated System Test and System Preliminary Design Review. NASA continues to pursue Solar Electric Propulsion (SEP) Technology Demonstration Mission partners and mature high-power SEP mission concepts. The recent announcement of the development of a Power and Propulsion Element (PPE) as the first element of an evolvable human architecture to Mars has replaced the Asteroid Redirect Robotic Mission as the most probable first application of the AEPS Hall thruster system. This high-power SEP capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned-exploration architecture. This paper presents the status of the combined NASA and Aerojet AEPS development activities and updated mission concept for implementation of the AEPS hardware as part of the ion propulsion system for a PPE

    Designed Inhibitors of Insulin-Degrading Enzyme Regulate the Catabolism and Activity of Insulin

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    Background: Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged. Methodology/Principal Findings: We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resulting compounds are ∼106 times more potent than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-à-vis conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor complex reveals a novel mode of inhibition based on stabilization of IDE's “closed,” inactive conformation. We show further that pharmacological inhibition of IDE potentiates insulin signaling by a mechanism involving reduced catabolism of internalized insulin. Conclusions/Significance: The inhibitors we describe are the first to potently and selectively inhibit IDE or indeed any member of this atypical zinc-metalloprotease superfamily. The distinctive structure of IDE's active site, and the mode of action of our inhibitors, suggests that it may be possible to develop inhibitors that cross-react minimally with conventional zinc-metalloproteases. Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes

    Environmental benefits of leaving offshore infrastructure in the ocean

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    © The Ecological Society of America The removal of thousands of structures associated with oil and gas development from the world's oceans is well underway, yet the environmental impacts of this decommissioning practice remain unknown. Similar impacts will be associated with the eventual removal of offshore wind turbines. We conducted a global survey of environmental experts to guide best decommissioning practices in the North Sea, a region with a substantial removal burden. In contrast to current regulations, 94.7% of experts (36 out of 38) agreed that a more flexible case-by-case approach to decommissioning could benefit the North Sea environment. Partial removal options were considered to deliver better environmental outcomes than complete removal for platforms, but both approaches were equally supported for wind turbines. Key considerations identified for decommissioning were biodiversity enhancement, provision of reef habitat, and protection from bottom trawling, all of which are negatively affected by complete removal. We provide recommendations to guide the revision of offshore decommissioning policy, including a temporary suspension of obligatory removal

    C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity

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    An intronic GGGGCC (G4C2) hexanucleotide repeat expansion inC9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 RNA can result in five different dipeptide repeat proteins (DPR: poly GA, poly GP, poly GR, poly PA, and poly PR), which aggregate into neuronal cytoplasmic and nuclear inclusions in affected patients, however their contribution to disease pathogenesis remains controversial. We show that among the DPR proteins, expression of poly GA in a cell culture model activates programmed cell death and TDP-43 cleavage in a dose-dependent manner. Dual expression of poly GA together with other DPRs revealed that poly GP and poly PA are sequestered by poly GA, whereas poly GR and poly PR are rarely co-localised with poly GA. Dual expression of poly GA and poly PA ameliorated poly GA toxicity by inhibiting poly GA aggregation both in vitro and in vivo in the chick embryonic spinal cord. Expression of alternative codon-derived DPRs in chick embryonic spinal cord confirmed in vitro data, revealing that each of the dipeptides caused toxicity, with poly GA being the most toxic. Further, in vivo expression of G4C2 repeats of varying length caused apoptotic cell death, but failed to generate DPRs. Together, these data demonstrate that C9-related toxicity can be mediated by either RNA or DPRs. Moreover, our findings provide evidence that poly GA is a key mediator of cytotoxicity and that cross-talk between DPR proteins likely modifies their pathogenic status in C9ALS/FTD

    LSST Science Book, Version 2.0

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    A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
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