147 research outputs found

    Thermoelectric power factor under strain-induced band-alignment in the half-Heuslers NbCoSn and TiCoSb

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    Band convergence is an effective strategy to improve the thermoelectric performance of complex bandstructure thermoelectric materials. Half-Heuslers are good candidates for band convergence studies because they have multiple bands near the valence bad edge that can be converged through various band engineering approaches providing power factor improvement opportunities. Theoretical calculations to identify the outcome of band convergence employ various approximations for the carrier scattering relaxation times (the most common being the constant relaxation time approximation) due to the high computational complexity involved in extracting them accurately. Here, we compare the outcome of strain-induced band convergence under two such scattering scenarios: i) the most commonly used constant relaxation time approximation and ii) energy dependent inter- and intra-valley scattering considerations for the half-Heuslers NbCoSn and TiCoSb. We show that the outcome of band convergence on the power factor depends on the carrier scattering assumptions, as well as the temperature. For both materials examined, band convergence improves the power factor. For NbCoSn, however, band convergence becomes more beneficial as temperature increases, under both scattering relaxation time assumptions. In the case of TiCoSb, on the other hand, constant relaxation time considerations also indicate that the relative power factor improvement increases with temperature, but under the energy dependent scattering time considerations, the relative improvement weakens with temperature. This indicates that the scattering details need to be accurately considered in band convergence studies to predict more accurate trends.Comment: 21 pages, 8 figures. arXiv admin note: text overlap with arXiv:1905.0795

    PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades

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    G-protein-coupled receptors sense extracellular chemical or physical stimuli and transmit these signals to distinct trimeric G-proteins. Activated Gα-proteins route signals to interconnected effector cascades, thus regulating thresholds, amplitudes and durations of signalling. Gαs- or Gαi-coupled receptor cascades are mechanistically conserved and mediate many sensory processes, including synaptic transmission, cell proliferation and chemotaxis. Here we show that a central, conserved component of Gαs-coupled receptor cascades, the regulatory subunit type-II (RII) of protein kinase A undergoes adenosine 3′-5′-cyclic monophosphate (cAMP)-dependent binding to Gαi. Stimulation of a mammalian Gαi-coupled receptor and concomitant cAMP-RII binding to Gαi, augments the sensitivity, amplitude and duration of Gαi:βγ activity and downstream mitogen-activated protein kinase signalling, independent of protein kinase A kinase activity. The mechanism is conserved in budding yeast, causing nutrient-dependent modulation of a pheromone response. These findings suggest a direct mechanism by which coincident activation of Gαs-coupled receptors controls the precision of adaptive responses of activated Gαi-coupled receptor cascades

    Regulation of Energy Stores and Feeding by Neuronal and Peripheral CREB Activity in Drosophila

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    The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved

    Evaluation of a novel nanocrystalline hydroxyapatite paste Ostim® in comparison to Alpha-BSM® - more bone ingrowth inside the implanted material with Ostim® compared to Alpha BSM®

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the performance a newly developed nanocrystalline hydroxyapatite, OSTIM<sup>® </sup>following functional implantation in femoral sites in thirty-eight sheep for 1, 2 or 3 months. Ostim<sup>® </sup>35 was compared to an established calcium phosphate, Alpha BSM<sup>®</sup>.</p> <p>Methods</p> <p>Biomechanical testing, μ-CT analysis, histological and histomorphological analyses were conducted to compare the treatments including evaluation of bone regeneration level, material degradation, implant biomechanical characteristics.</p> <p>Results</p> <p>The micro-computed tomography (μCT) analysis and macroscopic observations showed that Ostim<sup>® </sup>seemed to diffuse easily particularly when the defects were created in a cancellous bone area. Alpha BSM<sup>® </sup>remained in the defect.</p> <p>The performance of Ostim was good in terms of mechanical properties that were similar to Alpha BSM<sup>® </sup>and the histological analysis showed that the bone regeneration was better with Ostim<sup>® </sup>than with Alpha BSM<sup>®</sup>. The histomorphometric analysis confirmed the qualitative analysis and showed more bone ingrowth inside the implanted material with Ostim<sup>® </sup>when compared to Alpha BSM <sup>® </sup>at all time points.</p> <p>Conclusions</p> <p>The successful bone healing with osseous consolidation verifies the importance of the nanocrystalline hydroxyapatite in the treatment of metaphyseal osseous volume defects in the metaphyseal spongiosa.</p

    A Linear Framework for Time-Scale Separation in Nonlinear Biochemical Systems

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    Cellular physiology is implemented by formidably complex biochemical systems with highly nonlinear dynamics, presenting a challenge for both experiment and theory. Time-scale separation has been one of the few theoretical methods for distilling general principles from such complexity. It has provided essential insights in areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors, ion channels, gene regulation and post-translational modification. In each case, internal molecular complexity has been eliminated, leading to rational algebraic expressions among the remaining components. This has yielded familiar formulas such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these calculations are all instances of a single graph-theoretic framework. Despite the biochemical nonlinearity to which it is applied, this framework is entirely linear, yet requires no approximation. We show that elimination of internal complexity is feasible when the relevant graph is strongly connected. The framework provides a new methodology with the potential to subdue combinatorial explosion at the molecular level

    Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

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    Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
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