5,377 research outputs found

    Test results for composite specimens and elements containing joints and cutouts

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    A program was conducted to develop the technology for joints and cutouts in a composite fuselage that meets all design requirements of a large transport aircraft for the 1990s. An advanced trijet derivative of the DC-10 was selected as the baseline aircraft. Design and analysis of a 30-foot-long composite fuselage barrel provided a realistic basis for the test effort. The primary composite material was Hexcel F584 resin on 12 K IM6 fiber, in tape and broadgoods form. Fiberglass broadgoods were used in E-glass and S-glass fiber form in the cutout region of some panels. Additionally, injection-molded chopped graphite fiber/PEEK was used for longeron-to-frame shear clips. The test effort included four groups of test specimens, beginning with coupon specimens of mono-layer and cross-piled laminates, progressing through increasingly larger and more complex specimens, and ending with two 4- by 5-foot curved fuselage side panels. One of the side panels incorporated a transverse skin splice, while the second included two cabin window cutouts

    Alternative approaches to the legal, institutional and financial aspects of developing an inter-island electrical transmission cable system

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    This study (I) delineates three comprehensive alternative scenarios for the development, financing, construction, ownership, regulation and operation of an inter-island electric energy transmission cable systemDepartment of Planning and Economic Development, State of Hawai

    Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

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    Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced

    Coincidence between transcriptome analyses on different microarray platforms using a parametric framework

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    A parametric framework for the analysis of transcriptome data is demonstrated to yield coincident results when applied to data acquired using two different microarray platforms. Discrepancies among transcriptome studies are frequently reported, casting doubt on the reliability of collected data. The inconsistency among observations can be largely attributed to differences among the analytical frameworks employed for data analysis. The existing frameworks normalizes data against a standard determined from the data to be analyzed. In the present study, a parametric framework based on a strict model for normalization is applied to data acquired using an in-house printed chip and GeneChip. The framework is based on a common statistical characteristic of microarray data, and each data is normalized on the basis of a linear relationship with this model. In the proposed framework, the expressional changes observed and genes selected are coincident between platforms, achieving superior universality of data compared to other methods

    Association of Pre-ESRD Serum Calcium With Post-ESRD Mortality Among Incident ESRD Patients: A Cohort Study.

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    Albumin-corrected serum calcium (cSCa) decline at late stages of chronic kidney disease and rise after dialysis initiation. Although hypercalcemia is associated with higher mortality in end-stage renal disease (ESRD), there are scarce data on the impact of pre-ESRD cSCa on post-ESRD mortality. Therefore, we used a large national cohort of 21,826 US veterans who transitioned to dialysis in all US Department of Veterans Affairs health care facilities over 2009 to 2014 to examine the associations with all-cause and cause-specific post-ESRD mortality of (1) cSCa concentrations averaged over the last 6 months and (2) its rate of decline during the last 12 months before dialysis initiation. Mean concentrations and median rate of decline of cSCa were 9.3 ± 0.7 mg/dL and -0.15 (interquartile range -0.39 to 0.07) mg/dL/year, respectively. A total of 9596 patients died during the follow-up period (mean 1.9 years; total 41,541 patient-years) with an incidence rate of 23.1 per 100 patient-years. There was an independent linear association between higher cSCa with higher mortality (ptrend < 0.001). The mortality risk associated with cSCa ≥9.0 mg/dL was attenuated among active vitamin D users (pinteraction < 0.001). Patients with faster decline in cSCa showed lower mortality irrespective of baseline cSCa concentrations. These cSCa-mortality associations were stronger for noncardiovascular versus cardiovascular death. In conclusion, lower pre-ESRD cSCa and faster decline in cSCa were consistently and linearly associated with better post-ESRD survival among US veterans, especially for noncardiovascular death. Further studies are needed to determine if correcting hypocalcemia is beneficial or harmful and which intervention is preferred when indicated among patients transitioning to ESRD. © 2018 American Society for Bone and Mineral Research

    Pre-ESRD Depression and Post-ESRD Mortality in Patients with Advanced CKD Transitioning to Dialysis.

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    Background and objectivesDepression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis.Design, setting, participants, & measurementsFrom a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications.ResultsPatients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression.ConclusionPre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis

    Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

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    <p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

    Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter

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    We present a study of showers initiated by electrons, pions, kaons, and protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE scintillator-tungsten analogue hadronic calorimeter. The data were recorded at the CERN Super Proton Synchrotron in 2011. The analysis includes measurements of the calorimeter response to each particle type as well as measurements of the energy resolution and studies of the longitudinal and radial shower development for selected particles. The results are compared to Geant4 simulations (version 9.6.p02). In the study of the energy resolution we include previously published data with beam momenta from 1 GeV to 10 GeV recorded at the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table

    Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

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    A measurement of the production cross-section for top quark pairs(\ttbar) in pppp collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron ee or muon μ\mu) with large missing transverse energy and at least four jets, and dilepton (eeee, μμ\mu\mu or eμe\mu) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be 12.2±3.912.2 \pm 3.9 events and 2.5±0.62.5 \pm 0.6 events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde
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