2,937 research outputs found

    Energy Tunnels for Deicing of a Bridge Deck in Alpine Region

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    Roads and paved surfaces in cold climate are exposed to the formation of ice and snow deposition. These phenomena are related to high risks for vehicles and road users due to reduced friction. Deicing techniques are up to now mainly based on chemicals, especially salt. These substances induce chemical decay of concrete infrastructure elements and environmental harm. In order to overcome these drawbacks, the use of embedded hydraulic pipes with a hot carrier fluid below the paved surfaces has been proposed in last decades. This circuit can be part of a Ground Source Heat Pump (GSHP) system. Despite a number of examples of this technology have been proposed, very few of them included the application of energy tunnels. This paper focuses on the thermal activation of a tunnel lining in relation to an application for bridge deck deicing. A theoretical case study along an Alpine road has been considered as representative of a common situation of alternated bridges and tunnels. The numerical results show that the thermal activation of the tunnel lining can provide enough heat to keep the paved surface unfrozen even in protracted periods of low external temperatures

    Effects and Action Mechanisms of Berberine and Rhizoma coptidis on Gut Microbes and Obesity in High-Fat Diet-Fed C57BL/6J Mice

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    Gut microbes play important roles in regulating fat storage and metabolism. Rhizoma coptidis (RC) and its main active compound, berberine, have either antimicrobial or anti-obesity activities. In the present study, we hypothesize that RC exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes and berberine may be a key compound of RC. Gut microbes and glucose and lipid metabolism in high-fat diet-fed C57BL/6J (HFD) mice in vivo are investigated after RC and berberine treatments. The results show that RC (200 mg/kg) and berberine (200 mg/kg) significantly lower both body and visceral adipose weights, and reduce blood glucose and lipid levels, and decrease degradation of dietary polysaccharides in HFD mice. Both RC and berberine significantly reduce the proportions of fecal Firmicutes and Bacteroidetes to total bacteria in HFD mice. In the trial ex vivo, both RC and berberine significantly inhibit the growth of gut bacteria under aerobic and anaerobic conditions. In in vitro trials, both RC and berberine significantly inhibit the growth of Lactobacillus (a classical type of Firmicutes) under anaerobic conditions. Furthermore, both RC and berberine significantly increase fasting-induced adipose factor (Fiaf, a key protein negatively regulated by intestinal microbes) expressions in either intestinal or visceral adipose tissues. Both RC and berberine significantly increase mRNA expressions of AMPK, PGC1α, UCP2, CPT1α, and Hadhb related to mitochondrial energy metabolism, which may be driven by increased Fiaf expression. These results firstly suggest that antimicrobial activities of RC and berberine may result in decreasing degradation of dietary polysaccharides, lowering potential calorie intake, and then systemically activating Fiaf protein and related gene expressions of mitochondrial energy metabolism in visceral adipose tissues. Taken together, these action mechanisms may contribute to significant anti-obesity effects. Findings in the present study also indicate that pharmacological regulation on gut microbes can develop an anti-obesity strategy

    A low-power and high-speed True Random Number Generator using generated RTN

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    A novel True Random Number Generator (TRNG), using random telegraph noise (RTN) as the entropy source, is proposed to address speed, design area, power and cost simultaneously. For the first time, the proposed design breaks the inherent speed limitation and generates true random numbers up to 3Mbps with ultra-low power. This is over 10 times faster than the state-of-the-art RTN-TRNG. Moreover, the new design does not require selection of devices and thus avoids the use of large transistor array and laborious post-selection process. This reduces the circuit area and the cost. The proposed TRNG has been successfully validated on three different processes and they all passed the National Institute of Standards and Technology (NIST) tests, making it a suitable candidate for future cryptographically secured applications in the internet of things (IoT)

    Deciphering interplay between Salmonella invasion effectors

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    Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

    Kinetics of diffusion-controlled enzymatic reactions with charged substrates

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    The Debye-Hückel limiting law (DHL) has often been used to estimate rate constants of diffusion-controlled reactions under different ionic strengths. Two main approximations are adopted in DHL: one is that the solution of the linearized Poisson-Boltzmann equation for a spherical cavity is used to estimate the excess electrostatic free energy of a solution; the other is that details of electrostatic interactions of the solutes are neglected. This makes DHL applicable only at low ionic strengths and dilute solutions (very low substrate/solute concentrations). We show in this work that through numerical solution of the Poisson-Nernst-Planck equations, diffusion-reaction processes can be studied at a variety of conditions including realistically concentrated solutions, high ionic strength, and certainly with non-equilibrium charge distributions. Reaction rate coefficients for the acetylcholine-acetylcholinesterase system are predicted to strongly depend on both ionic strength and substrate concentration. In particular, they increase considerably with increase of substrate concentrations at a fixed ionic strength, which is open to experimental testing. This phenomenon is also verified on a simple model, and is expected to be general for electrostatically attracting enzyme-substrate systems

    An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

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    In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio

    ESD characterization of planar InGaAs devices

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    We present a comprehensive study of ESD reliability (TLP) on planar nMOSFETs with In0.53Ga0.47As as the channel material. Two types of traps are found during ESD stress. They are formed through independent mechanisms: transient Ef-lowering induced pre-existing e-traps discharging in the gate stack and hot hole induced e-traps generation through impact ionization in the InP buffer. These two types of traps explain the observed walk-out of off-state channel leakage current as well as the two-stage current conduction phenomena in the TLP measurement. The generated e-traps are permanent and can introduce detrimental conduction current harmful to the device performance. By properly selecting the buffer material, these defects can be removed

    Using genetics to understand the causal influence of higher BMI on depression

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     This is the final version. Available on open access from OUP via the DOI in this record.Background: Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women. Methods: We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to 'uncouple' the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways. Results: Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P < 0.05. Using a metabolically favourable adiposity genetic risk score, and meta-analysing data from the UK biobank and PGC, a genetically determined 1 SD higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals (OR: 1.26, 95% CI: 1.06, 1.50], P = 0.010), but with weaker statistical confidence. Conclusions: Higher BMI, with and without its adverse metabolic consequences, is likely to have a causal role in determining the likelihood of an individual developing depression.Diabetes Research and Wellness FoundationAustralian Research Training ProgramMedical Research CouncilWellcome TrustEuropean Research CouncilRoyal SocietyGillings Family FoundationDiabetes UKNational Institute for Health Research (NIHR

    Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

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    Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV
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