837 research outputs found

    Wind tunnel wall interference (January 1980 - May 1988): A selected, annotated bibliography

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    This selected bibliography lists 423 entries on the subject of wall interference during testing in wind tunnels. It is the third in a series of bibliographies on the subject. The first, NASA TM-87639, August 1986, is concerned with the reduction of wall interference by the use of adaptive walls. The second, NASA TP-89066, December 1986, is on wall interference in V/STOL and high lift testing. This, the third in the series, covers the wall interference literature published during the period January 1980 through May 1988, generally excluding those topics covered in the first two parts

    Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

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    Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

    Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial

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    BACKGROUND: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. METHODS: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. CONCLUSION: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events

    Building America Best Practices Series Volume 15: 40% Whole-House Energy Savings in the Hot-Humid Climate

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    This best practices guide is the 15th in a series of guides for builders produced by PNNL for the U.S. Department of Energy’s Building America program. This guide book is a resource to help builders design and construct homes that are among the most energy-efficient available, while addressing issues such as building durability, indoor air quality, and occupant health, safety, and comfort. With the measures described in this guide, builders in the hot-humid climate can build homes that have whole-house energy savings of 40% over the Building America benchmark with no added overall costs for consumers. The best practices described in this document are based on the results of research and demonstration projects conducted by Building America’s research teams. Building America brings together the nation’s leading building scientists with over 300 production builders to develop, test, and apply innovative, energy-efficient construction practices. Building America builders have found they can build homes that meet these aggressive energy-efficiency goals at no net increased costs to the homeowners. Currently, Building America homes achieve energy savings of 40% greater than the Building America benchmark home (a home built to mid-1990s building practices roughly equivalent to the 1993 Model Energy Code). The recommendations in this document meet or exceed the requirements of the 2009 IECC and 2009 IRC and those requirements are highlighted in the text. Requirements of the 2012 IECC and 2012 IRC are also noted in text and tables throughout the guide. This document will be distributed via the DOE Building America website: www.buildingamerica.gov

    The fraction of early-type galaxies in low redshift groups and clusters of galaxies

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    We examine the fraction of early-type (and spiral) galaxies found in groups and clusters of galaxies as a function of dark matter halo mass. We use morphological classifications from the Galaxy Zoo project matched to halo masses from both the C4 cluster catalogue and the Yang et al (2007) group catalogue. We find that the fraction of early-type (or spiral) galaxies remains constant (changing by less than 10%) over three orders of magnitude in halo mass (13<log MH/Msol/h<15.8). This result is insensitive to our choice of halo mass measure, from velocity dispersions or summed optical luminosity. Furthermore, we consider the morphology-halo mass relations in bins of galaxy stellar mass M*, and find that while the trend of constant fraction remains unchanged, the early-type fraction amongst the most massive galaxies (11<log M*/Msol/h <12) is a factor of three greater than lower mass galaxies (10<logM*/Msol/h<10.7). We compare our observational results with those of simulations presented in De Lucia et al (2011), as well as previous observational analyses, and semi-analytic bulge (or disc) dominated galaxies from the Millennium Simulation. We find the simulations recover similar trends as observed, but may over-predict the abundances of the most massive bulge dominated (early-type) galaxies. Our results suggest that most morphological transformation is happening on the group scale before groups merge into massive clusters. However, we show that within each halo a morphology-density relation remains: it is summing the total fraction to a self-similar scaled radius which results in a flat morphology-halo mass relationship.Comment: 9 page, 5 figures, modified to match accepted version (MNRAS

    <i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

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    Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

    Use of a multi-level mixed methods approach to study the effectiveness of a primary care progressive return to activity protocol after acute mild traumatic brain injury/concussion in the military

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    The large number of U.S. service members diagnosed with concussion/mild traumatic brain injury each year underscores the necessity for clear and effective clinical guidance for managing concussion. Relevant research continues to emerge supporting a gradual return to pre-injury activity levels without aggravating symptoms; however, available guidance does not provide detailed standards for this return to activity process. To fill this gap, the Defense and Veterans Brain Injury Center released a recommendation for primary care providers detailing a step-wise return to unrestricted activity during the acute phase of concussion. This guidance was developed in collaboration with an interdisciplinary group of clinical, military, and academic subject matter experts using an evidence-based approach. Systematic evaluation of the guidance is critical to ensure positive patient outcomes, to discover barriers to implementation by providers, and to identify ways to improve the recommendation. Here we describe a multi-level, mixed-methods approach to evaluate the recommendation incorporating outcomes from both patients and providers. Procedures were developed to implement the study within complex but ecologically-valid settings at multiple military treatment facilities and operational medical units. Special consideration was given to anticipated challenges such as the frequent movement of military personnel, selection of appropriate design and measures, study implementation at multiple sites, and involvement of multiple service branches (Army, Navy, and Marine Corps). We conclude by emphasizing the need to consider contemporary approaches for evaluating the effectiveness of clinical guidance

    Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

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    Introduction: Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. Methods: We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Results: Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Conclusions: Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. Trial registration ClinicalTrials.gov Identifier: NCT00099710

    Protecting biodiversity in British Columbia: Recommendations for developing species at risk legislation

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    British Columbia has the greatest biological diversity of any province or territory in Canada. Yet increasing numbers of species in British Columbia are threatened with extinction. The current patchwork of provincial laws and regulations has not effectively prevented species declines. Recently, the Provincial Government has committed to enacting an endangered species law. Drawing upon our scientific and legal expertise, we offer recommendations for key features of endangered species legislation that build upon strengths and avoid weaknesses observed elsewhere. We recommend striking an independent Oversight Committee to provide recommendations about listing species, organize Recovery Teams, and monitor the efficacy of actions taken. Recovery Teams would evaluate and prioritize potential actions for individual species or groups of species that face common threats or live in a common area, based on best available evidence (including natural and social science and Indigenous Knowledge). Our recommendations focus on implementing an adaptive approach, with ongoing and transparent monitoring and reporting, to reduce delays between determining when a species is at risk and taking effective actions to save it. We urge lawmakers to include this strong evidentiary basis for species recovery as they tackle the scientific and socioeconomic challenges of building an effective species at risk Act

    Protecting biodiversity in British Columbia: Recommendations for developing species at risk legislation

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    British Columbia has the greatest biological diversity of any province or territory in Canada. Yet increasing numbers of species in British Columbia are threatened with extinction. The current patchwork of provincial laws and regulations has not effectively prevented species declines. Recently, the Provincial Government has committed to enacting an endangered species law. Drawing upon our scientific and legal expertise, we offer recommendations for key features of endangered species legislation that build upon strengths and avoid weaknesses observed elsewhere. We recommend striking an independent Oversight Committee to provide recommendations about listing species, organize Recovery Teams, and monitor the efficacy of actions taken. Recovery Teams would evaluate and prioritize potential actions for individual species or groups of species that face common threats or live in a common area, based on best available evidence (including natural and social science and Indigenous Knowledge). Our recommendations focus on implementing an adaptive approach, with ongoing and transparent monitoring and reporting, to reduce delays between determining when a species is at risk and taking effective actions to save it. We urge lawmakers to include this strong evidentiary basis for species recovery as they tackle the scientific and socioeconomic challenges of building an effective species at risk Act
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