12,315 research outputs found

    A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase

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    This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway

    Experimental investigation of the impact of elastic turbulence on heat transfer in a serpentine channel

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    AbstractThe characteristics of convective heat transfer and fluid flow within a square cross-section serpentine channel are experimentally studied for two groups of polymeric viscoelastic fluids, shear-thinning and constant-viscosity Boger solutions. The elastic turbulence can be created by the non-linear interaction between elastic stresses generated within the flowing high-molecular-weight polymer solutions and the streamline curvature. In order to confirm elastic turbulence in this geometry, pressure drop across the serpentine channel was measured. The findings indicate that the measurements of non-dimensional pressure-drop increase approximately from 1.48 to 4.82 for viscoelastic solutions compared with the Newtonian fluid over a range of Weissenberg number from 4 to 211. The convective heat transfer enhances due to elastic turbulence by up to 200% for low polymer concentration (dilute) solutions and reaches up to 380% for higher polymer concentration (semi-dilute) solutions under creeping-flow conditions in comparison to that achieved by the equivalent Newtonian fluid flow at low Graetz number (up to 14.6). We propose a modified Weissenberg number which is able to approximately collapse the mean Nusselt number data for each solution group

    Sustainable Energy – Without the Hot Air

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    This is the electronic version of the book which is also available in hardback and paperback.We have an addiction to fossil fuels, and it’s not sustainable. The developed world gets 80% of its energy from fossil fuels; Britain, 90%. And this is unsustainable for three reasons. First, easily-accessible fossil fuels will at some point run out, so we’ll eventually have to get our energy from someplace else. Second, burning fossil fuels is having a measurable and very-probably dangerous effect on the climate. Avoiding dangerous climate change motivates an immediate change from our current use of fossil fuels. Third, even if we don’t care about climate change, a drastic reduction in Britain’s fossil fuel consumption would seem a wise move if we care about security of supply: continued rapid use of the North Sea Photo by Terry Cavner. oil and gas reserves will otherwise soon force fossil-addicted Britain to depend on imports from untrustworthy foreigners. (I hope you can hear my tongue in my cheek.) How can we get off our fossil fuel addiction? There’s no shortage of advice on how to “make a difference,” but the public is confused, uncertain whether these schemes are fixes or figleaves. People are rightly suspicious when companies tell us that buying their “green” product means we’ve “done our bit.” They are equally uneasy about national energy strategy. Are “decentralization” and “combined heat and power,” green enough, for example? The government would have us think so. But would these technologies really discharge Britain’s duties regarding climate change? Are windfarms “merely a gesture to prove our leaders’ environmental credentials”? Is nuclear power essential? We need a plan that adds up. The good news is that such plans can be made. The bad news is that implementing them will not be easy

    Sustainable Energy - without the hot air

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    The fact of global climate change is, famously, contested but, as the scientific evidence has accumulated, a broad consensus has emerged that warming of the earth is indeed happening and that this is anthropogenic. Now the main debate (we will ignore here the minority of naysayers) has moved from ‘whether’ (it is happening) to ‘what’ (to do about it); this debate is not going well, if the measure of success is practical actions, globally agreed (or even agreed on a nation-by-nation basis), to reduce the rate of emissions of greenhouse gases with the aim, ultimately, of reducing the actual amount of such gases in the atmosphere

    Quantitative analysis of regulatory flexibility under changing environmental conditions

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    The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock

    Informing investment to reduce inequalities: a modelling approach

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    Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities
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