516 research outputs found

    A novel, cost effective escharotomy simulator and trainee assessment

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    Over the last two decades, virtual reality, haptics, simulators, robotics, and other "advanced technologies" have emerged as important innovations in medical learning and practice. In the 21st century, however, it is important to continue to develop simple teaching aids which are available to large audiences in low and middle-income countries. We present a simple 'escharotomy simulator' which has been well received, resulting in an increase in knowledge, and an increase in confidence to carry out the procedure

    Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

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    This is the final version. It was first published by Wiley in The Journal of Physiology at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.275263/abstract.Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species (ROS) generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n=40) were given water supplemented with 0.7 mmol/L NaCl (as control) or 0.7 mmol/L NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n=10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac L-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics

    Modeling and Analysis of Space Based Transceivers

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    This paper presents the tool chain, methodology, and results of an on-going study being performed jointly by Space Communication Experts at NASA Glenn Research Center (GRC), General Dynamics C4 Systems (GD), and Southwest Research Institute (SwRI). The team is evaluating the applicability and tradeoffs concerning the use of Software Defined Radio (SDR) technologies for Space missions. The Space Telecommunications Radio Systems (STRS) project is developing an approach toward building SDR-based transceivers for space communications applications based on an accompanying software architecture that can be used to implement transceivers for NASA space missions. The study is assessing the overall cost and benefit of employing SDR technologies in general, and of developing a software architecture standard for its space SDR transceivers. The study is considering the cost and benefit of existing architectures, such as the Joint Tactical Radio Systems (JTRS) Software Communications Architecture (SCA), as well as potential new space-specific architectures

    Suppression of erythropoiesis by dietary nitrate

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    In mammals, hypoxia-triggered erythropoietin release increases red blood cell mass to meet tissue oxygen demands. Using male Wistar rats, we unmask a previously unrecognized regulatory pathway of erythropoiesis involving suppressor control by the NO metabolite and ubiquitous dietary component nitrate. We find that circulating hemoglobin levels are modulated by nitrate at concentrations achievable by dietary intervention under normoxic and hypoxic conditions; a moderate dose of nitrate administered via the drinking water (7 mg NaNO3/kg body weight/d) lowered hemoglobin concentration and hematocrit after 6 d compared with nonsupplemented/NaCl-supplemented controls. The underlying mechanism is suppression of hepatic erythropoietin expression associated with the downregulation of tissue hypoxia markers, suggesting increased pO2. At higher nitrate doses, however, a partial reversal of this effect occurred; this was accompanied by increased renal erythropoietin expression and stabilization of hypoxia-inducible factors, likely brought about by the relative anemia. Thus, hepatic and renal hypoxia-sensing pathways act in concert to modulate hemoglobin in response to nitrate, converging at an optimal minimal hemoglobin concentration appropriate to the environmental/physiologic situation. Suppression of hepatic erythropoietin expression by nitrate may thus act to decrease blood viscosity while matching oxygen supply to demand, whereas renal oxygen sensing could act as a brake, averting a potentially detrimental fall in hematocrit.—Ashmore, T., Fernandez, B. O., Evans, C. E., Huang, Y., Branco-Price, C., Griffin, J. L., Johnson, R. S., Feelisch, M., and Murray, A. J. Suppression of erythropoiesis by dietary nitrate

    Multi-objective engineering shape optimization using differential evolution interfaced to the Nimrod/O tool

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    This paper presents an enhancement of the Nimrod/O optimization tool by interfacing DEMO, an external multiobjective optimization algorithm. DEMO is a variant of differential evolution – an algorithm that has attained much popularity in the research community, and this work represents the first time that true multiobjective optimizations have been performed with Nimrod/O. A modification to the DEMO code enables multiple objectives to be evaluated concurrently. With Nimrod/O’s support for parallelism, this can reduce the wall-clock time significantly for compute intensive objective function evaluations. We describe the usage and implementation of the interface and present two optimizations. The first is a two objective mathematical function in which the Pareto front is successfully found after only 30 generations. The second test case is the three-objective shape optimization of a rib-reinforced wall bracket using the Finite Element software, Code_Aster. The interfacing of the already successful packages of Nimrod/O and DEMO yields a solution that we believe can benefit a wide community, both industrial and academic

    Modular and predictable assembly of porous organic molecular crystals

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    Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

    Fluctuation Theorems for Entropy Production and Heat Dissipation in Periodically Driven Markov Chains

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    Asymptotic fluctuation theorems are statements of a Gallavotti-Cohen symmetry in the rate function of either the time-averaged entropy production or heat dissipation of a process. Such theorems have been proved for various general classes of continuous-time deterministic and stochastic processes, but always under the assumption that the forces driving the system are time independent, and often relying on the existence of a limiting ergodic distribution. In this paper we extend the asymptotic fluctuation theorem for the first time to inhomogeneous continuous-time processes without a stationary distribution, considering specifically a finite state Markov chain driven by periodic transition rates. We find that for both entropy production and heat dissipation, the usual Gallavotti-Cohen symmetry of the rate function is generalized to an analogous relation between the rate functions of the original process and its corresponding backward process, in which the trajectory and the driving protocol have been time-reversed. The effect is that spontaneous positive fluctuations in the long time average of each quantity in the forward process are exponentially more likely than spontaneous negative fluctuations in the backward process, and vice-versa, revealing that the distributions of fluctuations in universes in which time moves forward and backward are related. As an additional result, the asymptotic time-averaged entropy production is obtained as the integral of a periodic entropy production rate that generalizes the constant rate pertaining to homogeneous dynamics

    Heritability and genome-wide analyses of problematic peer relationships during childhood and adolescence

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    Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4–17 years), and a UK twin sample (TEDS, 4–11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4–11 years, 0.60 < twin-h 2 ≤ 0.71) but genetically heterogeneous from age to age (4–11 years, twin-r g = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4–12 years, 0.02<GCTA−h2Meta ≤ 0.11) though these influences become stronger in adolescence (13–17 years, 0.14<GCTA−h2ALSPAC ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10−5) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence

    Search for the Proton Decay Mode proton to neutrino K+ in Soudan 2

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    We have searched for the proton decay mode proton to neutrino K+ using the one-kiloton Soudan 2 high resolution calorimeter. Contained events obtained from a 3.56 kiloton-year fiducial exposure through June 1997 are examined for occurrence of a visible K+ track which decays at rest into mu+ nu or pi+ pi0. We found one candidate event consistent with background, yielding a limit, tau/B > 4.3 10^{31} years at 90% CL with no background subtraction.Comment: 13 pages, Latex, 3 tables and 3 figures, Accepted by Physics Letters
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