1,720 research outputs found

    The Cerebellum and SIDS: Disordered Breathing in a Mouse Model of Developmental Cerebellar Purkinje Cell Loss during Recovery from Hypercarbia.

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    The cerebellum assists coordination of somatomotor, respiratory, and autonomic actions. Purkinje cell alterations or loss appear in sudden infant death and sudden death in epilepsy victims, possibly contributing to the fatal event. We evaluated breathing patterns in 12 wild-type (WT) and Lurcher mutant mice with 100% developmental cerebellar Purkinje cell loss under baseline (room air), and recovery from hypercapnia, a concern in sudden death events. Six mutant and six WT mice were exposed to 4-min blocks of increasing CO2 (2, 4, 6, and 8%), separated by 4-min recovery intervals in room air. Breath-by-breath patterns, including depth of breathing and end-expiratory pause (EEP) durations during recovery, were recorded. No baseline genotypic differences emerged. However, during recovery, EEP durations significantly lengthened in mutants, compared to WT mice, following the relatively low levels of CO2 exposure. Additionally, mutant mice exhibited signs of post-sigh disordered breathing during recovery following each exposure. Developmental cerebellar Purkinje cell loss significantly affects compensatory breathing patterns following mild CO2 exposure, possibly by inhibiting recovery from elevated CO2. These data implicate cerebellar Purkinje cells in the ability to recover from hypercarbia, suggesting that neuropathologic changes or loss of these cells contribute to inadequate ventilatory recovery to increased environmental CO2. Multiple disorders, including sudden infant death syndrome (SIDS) and sudden unexpected death in epilepsy (SUDEP), appear to involve both cardiorespiratory failure and loss or injury to cerebellar Purkinje cells; the findings support the concept that such neuropathology may precede and exert a prominent role in these fatal events

    Studies in discrete dynamic programming

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    Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering, 1958.Vita.Includes bibliographical references (leaf 108).by Ronald Arthur Howard.Sc.D

    Study of helicopterroll control effectiveness criteria

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    A study of helicopter roll control effectiveness based on closed-loop task performance measurement and modeling is presented. Roll control critieria are based on task margin, the excess of vehicle task performance capability over the pilot's task performance demand. Appropriate helicopter roll axis dynamic models are defined for use with analytic models for task performance. Both near-earth and up-and-away large-amplitude maneuvering phases are considered. The results of in-flight and moving-base simulation measurements are presented to support the roll control effectiveness criteria offered. This Volume contains the theoretical analysis, simulation results and criteria development

    A 4-m evolvable space telescope configured for NASA's HabEx Mission: the initial stage of LUVOIR

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    Previous papers have described our concept for a large telescope that would be assembled in space in several stages (in different configurations) over a period of fifteen to 20 years. Spreading the telescope development, launch and operations cost over 20 years would minimize the impact on NASA’s annual budget and drastically shorten the time between program start and “first light” for this space observatory. The first Stage of this Evolvable Space Telescope (EST) would consist of an instrument module located at the prime focus of three 4-meter hexagonal mirrors arranged in a semi-circle to form one-half of a 12-m segmented mirror. After several years three additional 4-m mirrors would be added to create a 12-m filled aperture. Later, twelve more 4-m mirrors will be added to this Stage 2 telescope to create a 20-m filled aperture space telescope. At each stage the telescope would have an unparalleled capability for UVOIR observations, and the results of these observations will guide the evolution of the telescope and its instruments. In this paper we describe our design concept for an initial configuration of our Evolvable Space Telescope that can meet the requirements of the 4-m version of the HabEx spacecraft currently under consideration by NASA’s Habitable Exoplanet Science and Technology Definition Team. This “Stage Zero” configuration will have only one 4-m mirror segment with the same 30-m focal length and a prime focus coronagraph with normal incidence optics to minimize polarization effects. After assembly and checkout in cis-lunar space, the telescope would transfer to a Sun-Earth L2 halo orbit and obtain high sensitivity, high resolution, high contrast UVOIR observations that address the scientific objectives of the Habitable-Exoplanet Imaging Missions

    Aircraft/island/ship/satellite intercomparison: Preliminary results from July 16, 1987

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    The First ISCCP Regional Experiment (FIRE) objective of validating and improving satellite algorithms for inferring cloud properties from satellite radiances was one of the central motivating factors in the design of the specific field experimental strategies used in the July, 1987 marine stratocumulus intensive field observations (IFO). The in situ measuring platforms were deployed to take maximum advantage of redundant measurements (for intercomparison of the in situ sensors) and to provide optimal coverage within satellite images. One of the most ambitious of these strategies was the attempt to coordinate measurements from San Nicolas Island (SNI), the R/V Pt. Sur, the meteorological aircraft, and the satellites. For the most part, this attempt was frustrated by flight restrictions in the vicinity of SNI. The exception was the mission of July 16, 1987, which achieved remarkable success in the coordination of the platforms. This presentation concerns operations conducted by the National Center for Atmospheric Research (NCAR) Electra and how data from the Electra can be integrated with and compared to data from the Pt. Sur, SNI, and the satellites. The focus is on the large-scale, integrated picture of the conditions on July 16 from the perspective of the Electra's flight operations

    CHOP links endoplasmic reticulum stress to NF-κB activation in the pathogenesis of nonalcoholic steatohepatitis

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    Free fatty acid induction of inflammation and cell death is an important feature of nonalcoholic steatohepatitis (NASH) and has been associated with disruption of the endoplasmic reticulum and activation of the Unfolded Protein Response (UPR). Following chronic UPR activation, the transcription factor CHOP (GADD153/DDIT3) triggers cell death; however, the mechanisms linking the UPR or CHOP to hepatoceullular injury and inflammation in the pathogenesis of NASH are not well understood. Using HepG2 and primary human hepatocytes, we found that CHOP induces cell death and inflammatory responses following saturated free fatty acid exposure by activating NF-κB through a pathway involving IRAK2 expression, resulting in secretion of cytokines IL-8 and TNFα directly from hepatocytes. TNFα facilitates hepatocyte death upon exposure to saturated free fatty acids and secretion of both IL-8 and TNFα contribute to inflammation. Interestingly, CHOP/NF-κB signaling is not conserved in primary rodent hepatocytes. Our studies suggest that CHOP plays a vital role in the pathophysiology of NASH through induction of secreted factors that trigger inflammation and hepatocellular death via a signaling pathway specific to human hepatocytes

    The association of remotely-sensed outdoor temperature with blood pressure levels in REGARDS: a cross-sectional study of a large, national cohort of African-American and white participants

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    <p>Abstract</p> <p>Background</p> <p>Evidence is mounting regarding the clinically significant effect of temperature on blood pressure.</p> <p>Methods</p> <p>In this cross-sectional study the authors obtained minimum and maximum temperatures and their respective previous week variances at the geographic locations of the self-reported residences of 26,018 participants from a national cohort of blacks and whites, aged 45+. Linear regression of data from 20,623 participants was used in final multivariable models to determine if these temperature measures were associated with levels of systolic or diastolic blood pressure, and whether these relations were modified by stroke-risk region, race, education, income, sex hypertensive medication status, or age.</p> <p>Results</p> <p>After adjustment for confounders, same-day maximum temperatures 20°F lower had significant associations with 1.4 mmHg (95% CI: 1.0, 1.9) higher systolic and 0.5 mmHg (95% CI: 0.3, 0.8) higher diastolic blood pressures. Same-day minimum temperatures 20°F lower had a significant association with 0.7 mmHg (95% CI: 0.3, 1.0) higher systolic blood pressures but no significant association with diastolic blood pressure differences. Maximum and minimum previous-week temperature variabilities showed significant but weak relationships with blood pressures. Parameter estimates showed effect modification of negligible magnitude.</p> <p>Conclusions</p> <p>This study found significant associations between outdoor temperature and blood pressure levels, which remained after adjustment for various confounders including season. This relationship showed negligible effect modification.</p

    Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

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    BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes
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