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We have identified three yeast genes, KES1, HES1 and OSH1, whose products show homology to the human oxysterol binding protein (OSBP). Mutations in these genes resulted in pleiotropic sterol-related phenotypes. These include tryptophan-transport defects and nystatin resistance, shown by double and triple mutants. In addition, mutant combinations showed small but apparently cumulative reductions in membrane ergosterol levels. The three yeast genes are also functionally related as overexpression of HES1 or KES1 alleviated the tryptophan-transport defect in kes1Δ or osh1Δ mutants, respectively. Our study implicates this new yeast gene family in ergosterol synthesis and provides comparative evidence of a role for human OSBP in cholesterol synthesis.  相似文献   
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R. V. McDonald and S. Siegel (see record 2004-10475-001) present new evidence for the idea that opioid drug-opposite responses can become conditioned to cues of initial drug onset and that they could, therefore, play a role in the development of tolerance of some drug effects and a role in the elicitation of withdrawal-like symptoms in cases in which addicted individuals are exposed to small doses of the drug they normally consume. In this comment, some puzzling features of the data are discussed, and alternative explanations are suggested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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Utilitarian and economic theories of deterrence hold that the relation of the penalty to the misdeed should be irrelevant. In 5 experiments using hypothetical cases, judgments of penalties depended on whether this relation was in kind (IK) or out of kind (OK). When victims were identifiable, IK penalties were higher than OK and preferred to OK. Subjects seemed to confuse penalties and compensation. When there were no identifiable victims (e.g., environmental damage), IK penalties were preferred, but OK penalties were higher. Here, OK judgments were more uncertain, and subjects preferred to err on the side of overpunishing. The results can be explained in terms of overgeneralization of usually useful heuristics. Alternative hypotheses concerning aggression and scale compatibility are rejected. The findings have implications for the setting of penalties in legal cases (e.g., the Exxon Valdez) and for lay theories of punishment in nonlegal settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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The thermal diffusivity of mullite-ZrO2-SiCw materials was determined from 25° to 1000°C for composites in which the ZrO2 had different amounts of monoclinic and tetragonal phase, and varying SiC w content. At 25°C the thermal diffusivity of the matrix materials increased with increasing amounts of monoclinic phase, and little or no anisotropy was seen. Composites with SiC w additions showed significant increases in thermal diffusivity and anisotropy as compared with the matrix materials. With increasing temperature, thermal diffusivities of the matrices and their respective composites decreased, and at 1000°C differences were small. Specific heat was determined from 25° to 700°C and thermal conductivity values calculated. Specific heat increased with temperature and was not composition dependent, except for one sample. Thermal conductivity values as a function of temperature followed the same trends as the thermal diffusivity values.  相似文献   
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This article explores the role of qualitative and collaborative methods when undertaking evaluation research into local community safety partnerships and neighbourhood strategies. It draws on recent examples of research and evaluation studies of regeneration and community safety programmes in a number of cities and towns in England. The discussion is set against the background of the major changes in policy relating to crime and community safety, particularly the introduction of Crime and Disorder Partnerships and their engagement with local communities. The value of qualitative methods in exploring some key questions is discussed, particularly within a collaborative approach to policy research.  相似文献   
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Water Resources Management - A traditional cost-benefit analysis of potential water interventions in a given locality is a laborious and time-intensive process. To help decision makers identify...  相似文献   
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The role of regulatory light chains (RLCs) in cardiac muscle function has been elucidated progressively over the past decade. The RLCs are among the earliest expressed markers during cardiogenesis and persist through adulthood. Failing hearts have shown reduced RLC phosphorylation levels and that restoring baseline levels of RLC phosphorylation is necessary for generating optimal force of muscle contraction. The signalling mechanisms triggering changes in RLC phosphorylation levels during disease progression remain elusive. Uncovering this information may provide insights for better management of heart failure patients. Given the cardiac chamber-specific expression of RLC isoforms, ventricular RLCs have facilitated the identification of mature ventricular cardiomyocytes, opening up possibilities of regenerative medicine. This review consolidates the standing of RLCs in cardiac development and disease and highlights knowledge gaps and potential therapeutic advancements in targeting RLCs.  相似文献   
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Pregnant rats were fed a high carbohydrate diet containing either 1% trilinolein or 1% trilinolein with 0.2% methyl sterculate from 18 day gestation to 21 day postpartum. The pups were weaned at 21 days and continued on the same diet for an additional 10 days. The microsomal stearyl CoA desaturase activities of the liver were effectively inhibited. Liver triglycerides showed increases in the saturated fatty acids concentrations at the expense of the corresponding monoenes. The concentration ofcis 6–7 octadecenoic acid was elevated. In liver phospholipids, the concentration of stearic acid was increased without a corresponding decrease in the oleic acid content. A drastic decrease in the nervonic acid (24∶1, n−9) concentration of liver sphingomyelin was observed. The lipids of the brain did not contain sterculic acid, and brain desaturase activity was unaffected. There was no significant change in the concentration of monoenoic acids from 16∶1 to 22∶1. However, nervonic acid was decreased by 32%. These results suggest that brain nervonic acid may be derived from a precursor other than oleic acid.  相似文献   
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