237 research outputs found

    Individual thermal comfort prediction using classification tree model based on physiological parameters and thermal history in winter

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    Individual thermal comfort models based on physiological parameters could improve the efficiency of the personal thermal comfort control system. However, the effect of thermal history has not been fully addressed in these models. In this study, climate chamber experiments were conducted in winter using 32 subjects who have different indoor and outdoor thermal histories. Two kinds of thermal conditions were investigated: the temperature dropping (24–16 °C) and severe cold (12 °C) conditions. A simplified method using historical air temperature to quantify the thermal history was proposed and used to predict thermal comfort and thermal demand from physical or physiological parameters. Results show the accuracies of individual thermal sensation prediction was low to about 30% by using the PMV index in cold environments of this study. Base on the sensitivity and reliability of physiological responses, five local skin temperatures (at hand, calf, head, arm and thigh) and the heart rate are optimal input parameters for the individual thermal comfort model. With the proposed historical air temperature as an additional input, the general accuracies using classification tree model C5.0 were increased up by 15.5% for thermal comfort prediction and up by 29.8% for thermal demand prediction. Thus, when predicting thermal demands in winter, the factor of thermal history should be considered

    ORP2, a cholesterol transporter, regulates angiogenic signaling in endothelial cells

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    https://doi.org/10.1096/fj.202000202ROxysterol-binding protein-related protein 2 (ORP2), a cholesterol-PI(4,5)P(2)countercurrent transporter, was recently identified as a novel regulator of plasma membrane (PM) cholesterol and PI(4,5)P(2)content in HeLa cells. Here, we investigate the role of ORP2 in endothelial cell (EC) cholesterol and PI(4,5)P(2)distribution, angiogenic signaling, and angiogenesis. We show that ORP2 knock-down modifies the distribution of cholesterol accessible to a D4H probe, between late endosomes and the PM. Depletion of ORP2 from ECs inhibits their angiogenic tube formation capacity, alters the gene expression of angiogenic signaling pathways such as VEGFR2, Akt, mTOR, eNOS, and Notch, and reduces EC migration, proliferation, and cell viability. We show that ORP2 regulates the integrity of VEGFR2 at the PM in a cholesterol-dependent manner, the depletion of ORP2 resulting in proteolytic cleavage by matrix metalloproteinases, and reduced activity of VEGFR2 and its downstream signaling. We demonstrate that ORP2 depletion increases the PM PI(4,5)P(2)coincident with altered F-actin morphology, and reduces both VEGFR2 and cholesterol in buoyant raft membranes. Moreover, ORP2 knock-down suppresses the expression of the lipid raft-associated proteins VE-cadherin and caveolin-1. Analysis of the retinal microvasculature in ORP2 knock-out mice generated during this study demonstrates the subtle alterations of morphology characterized by reduced vessel length and increased density of tip cells and perpendicular sprouts. Gene expression changes in the retina suggest disturbance of sterol homeostasis, downregulation of VE-cadherin, and a putative disturbance of Notch signaling. Our data identifies ORP2 as a novel regulator of EC cholesterol and PI(4,5)P(2)homeostasis and cholesterol-dependent angiogenic signaling.Peer reviewe

    Alterations of Cardiac Protein Kinases in Cyclic Nucleotide-Dependent Signaling Pathways in Human Ischemic Heart Failure

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    ObjectivesImpaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and signaling pathways in patients with IHD with an effort to discover potential therapeutic strategies.MethodsCardiac kinase activity in IHD left ventricle (LV) and the related signaling pathways were investigated by kinomics, transcriptomics, proteomics, and integrated multi-omics approach.ResultsProtein kinase A (PKA) and protein kinase G (PKG) ranked on top in the activity shift among the cardiac kinases. In the IHD LVs, PKA activity decreased markedly compared with that of controls (62% reduction, p = 0.0034), whereas PKG activity remained stable, although the amount of PKG protein increased remarkably (65%, p = 0.003). mRNA levels of adenylate cyclases (ADCY 1, 3, 5, 9) and cAMP-hydrolysing phosphodiesterases (PDE4A, PDE4D) decreased significantly, although no statistically significant alterations were observed in that of PKGs (PRKG1 and PRKG2) and guanylate cyclases (GUCYs). The gene expression of natriuretic peptide CNP decreased remarkably, whereas those of BNP, ANP, and neprilysin increased significantly in the IHD LVs. Proteomics analysis revealed a significant reduction in protein levels of “Energy metabolism” and “Muscle contraction” in the patients. Multi-omics integration highlighted intracellular signaling by second messengers as the top enriched Reactome pathway.ConclusionThe deficiency in cAMP/PKA signaling pathway is strongly implicated in the pathogenesis of IHD. Natriuretic peptide CNP could be a potential therapeutic target for the modulation of cGMP/PKG signaling.Peer reviewe

    The Generationing of Power: A Comparison of Child-Parent and Sibling Relations in Scotland

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    The paper concentrates on an exploration of power relations within families. The paper discusses parental power in relation to legitimacy, household resources and children’s anticipated reactions of adult discipline. The nature of sibling power is highlighted before exploring the reciprocal expectations of sibling and child-parent interactions. The paper ends by suggesting that the generationing of power relations can lead to differing degrees of backstage and frontstage performances within the home

    Transfer of Health for All policy – What, how and in which direction? A two-case study

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    BACKGROUND: This article explores the transfer of World Health Organization's (WHO) policy initiative Health for All by the Year 2000 (HFA2000) into national contexts by using the changes in the public health policies of Finland and Portugal from the 1970's onward and the relationship of these changes to WHO policy development as test cases. Finland and Portugal were chosen to be compared as they represent different welfare state types and as the paradigmatic transition from the old to new public health is assumed to be related to the wider welfare state development. METHODS: The policy transfer approach is used as a conceptual tool to analyze the possible policy changes related to the adaptation of HFA into the national context. To be able to analyze not only the content but also the contextual conditions of policy transfer Kingdon's analytical framework of policy analysis is applied. CONCLUSIONS: Our analysis suggests that no significant change of health promotion policy resulted from the launch of HFA program neither in Finland nor in Portugal. Instead the changes that occurred in both countries were of incremental nature, in accordance with the earlier policy choices, and the adaptation of HFA program was mainly applied to the areas where there were national traditions

    Development Environment to Increase Efficiency of Electric Traction Motors

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