10,286 research outputs found

    The Air-temperature Response to Green/blue-infrastructure Evaluation Tool (TARGET v1.0) : an efficient and user-friendly model of city cooling

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    The adverse impacts of urban heat and global climate change are leading policymakers to consider green and blue infrastructure (GBI) for heat mitigation benefits. Though many models exist to evaluate the cooling impacts of GBI, their complexity and computational demand leaves most of them largely inaccessible to those without specialist expertise and computing facilities. Here a new model called The Air-temperature Response to Green/blue-infrastructure Evaluation Tool (TARGET) is presented. TARGET is designed to be efficient and easy to use, with fewer user-defined parameters and less model input data required than other urban climate models. TARGET can be used to model average street-level air temperature at canyon-to-block scales (e.g. 100 m resolution), meaning it can be used to assess temperature impacts of suburb-to-city-scale GBI proposals. The model aims to balance realistic representation of physical processes and computation efficiency. An evaluation against two different datasets shows that TARGET can reproduce the magnitude and patterns of both air temperature and surface temperature within suburban environments. To demonstrate the utility of the model for planners and policymakers, the results from two precinct-scale heat mitigation scenarios are presented. TARGET is available to the public, and ongoing development, including a graphical user interface, is planned for future work

    Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

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    The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

    Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

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    Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

    Do children\u27s food preferences align with dietary recommendations?

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    Objectives: To examine how Australian children\u27s reported everyday food preferences reflect dietary recommendations, and the impact of sociodemographic factors on these associations.Design:&nbsp; Cross-sectional survey.Setting/subjects: Three hundred and seventy-one parents of children aged 2&ndash;5 years, recruited from three socio-economic groups in two Australian cities, completed a survey on their child\u27s liking for 176 foods and drinks on a 5-point Likert scale in addition to demographic descriptors. Preferences were compared with the recommendations of the Dietary Guidelines for Children and Adolescents in Australia and the Australian Guide to Healthy Eating.Results:&nbsp; Foods in the Extra Foods (non-nutritious foods) and Cereals groups of the Australian Guide to Healthy Eating were highly liked (mean: 4.02 and 4.01, respectively), whilst foods in the Vegetables group were liked least (mean: 3.01). A large percentage of foods in the Cereals and Extra Foods groups were liked (64% and 56%, respectively) in contrast to the other food groups, especially Vegetables (7%). Children liked foods that were higher in sugar (r = 0.29, P &lt; 0.0001) and more energy-dense (r = 0.34, P &lt; 0.0001) but not those higher in saturated fat (r = 0.16, P = 0.03), total fat (r = 0.12, P = 0.12) or sodium (r = 0.10, P = 0.18). Sociodemographic variables (e.g. socio-economic status, parental education, children\u27s age and sex) explained little of the variation in children\u27s food preferences.Conclusions:&nbsp; Australian pre-school children\u27s food preferences align with dietary guidelines in some respects, but not others. Interventions are needed to shift children\u27s preferences away from non-nutritious foods that are high in energy density and sugar, and towards vegetables and fruits.<br /

    Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

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    Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

    Run 2 Upgrades to the CMS Level-1 Calorimeter Trigger

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    The CMS Level-1 calorimeter trigger is being upgraded in two stages to maintain performance as the LHC increases pile-up and instantaneous luminosity in its second run. In the first stage, improved algorithms including event-by-event pile-up corrections are used. New algorithms for heavy ion running have also been developed. In the second stage, higher granularity inputs and a time-multiplexed approach allow for improved position and energy resolution. Data processing in both stages of the upgrade is performed with new, Xilinx Virtex-7 based AMC cards.Comment: 10 pages, 7 figure
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