642 resultados para reading system
Resumo:
We diagnose forcing and climate feedbacks in benchmark sensitivity experiments with the new Met Office Hadley Centre Earth system climate model HadGEM2-ES. To identify the impact of newly-included biogeophysical and chemical processes, results are compared to a parallel set of experiments performed with these processes switched off, and different couplings with the biogeochemistry. In abrupt carbon dioxide quadrupling experiments we find that the inclusion of these processes does not alter the global climate sensitivity of the model. However, when the change in carbon dioxide is uncoupled from the vegetation, or when the model is forced with a non-carbon dioxide forcing – an increase in solar constant – new feedbacks emerge that make the climate system less sensitive to external perturbations. We identify a strong negative dust-vegetation feedback on climate change that is small in standard carbon dioxide sensitivity experiments due to the physiological/fertilization effects of carbon dioxide on plants in this model.
Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system
Resumo:
BACKGROUND: Bile acids (BAs) regulate cells by activating nuclear and membrane-bound receptors. G protein coupled bile acid receptor 1 (GpBAR1) is a membrane-bound G-protein-coupled receptor that can mediate the rapid, transcription-independent actions of BAs. Although BAs have well-known actions on motility and secretion, nothing is known about the localization and function of GpBAR1 in the gastrointestinal tract. METHODS: We generated an antibody to the C-terminus of human GpBAR1, and characterized the antibody by immunofluorescence and Western blotting of HEK293-GpBAR1-GFP cells. We localized GpBAR1 immunoreactivity (IR) and mRNA in the mouse intestine, and determined the mechanism by which BAs activate GpBAR1 to regulate intestinal motility. KEY RESULTS: The GpBAR1 antibody specifically detected GpBAR1-GFP at the plasma membrane of HEK293 cells, and interacted with proteins corresponding in mass to the GpBAR1-GFP fusion protein. GpBAR1-IR and mRNA were detected in enteric ganglia of the mouse stomach and small and large intestine, and in the muscularis externa and mucosa of the small intestine. Within the myenteric plexus of the intestine, GpBAR1-IR was localized to approximately 50% of all neurons and to >80% of inhibitory motor neurons and descending interneurons expressing nitric oxide synthase. Deoxycholic acid, a GpBAR1 agonist, caused a rapid and sustained inhibition of spontaneous phasic activity of isolated segments of ileum and colon by a neurogenic, cholinergic and nitrergic mechanism, and delayed gastrointestinal transit. CONCLUSIONS & INFERENCES: G protein coupled bile acid receptor 1 is unexpectedly expressed in enteric neurons. Bile acids activate GpBAR1 on inhibitory motor neurons to release nitric oxide and suppress motility, revealing a novel mechanism for the actions of BAs on intestinal motility.
Resumo:
G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and trafficking of GPCRs in the nervous system. It summarizes how receptor modifications influence trafficking, discusses mechanisms that regulate GPCR trafficking to and from the plasma membrane, reviews the relationship between trafficking and signaling, and considers the implications of GPCR trafficking to drug development.
Resumo:
Due to the requirement to demonstrate financial feasibility of policy proposals and scheme-specific planning obligations, development viability and development appraisal have become core themes in the English planning system. The objective of this paper is to evaluate the application of development appraisal in practice. The paper reviews the literature and the models available to assess the viability of development and analyses a sample 19 development viability appraisals to identify practice. The paper concludes that the practice of development appraisal deviates significantly from the tenets of capital budgeting theory. In particular, in addition to a propensity to oversimplify the timing of income and expenditure, the way in which debt, developer’s return and value and cost change are handled in practice illustrates a major gap between mainstream capital budgeting theory and development appraisal in practice.
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This paper analyses the quality of debate surrounding the UK’s 2011 electoral reform referendum as represented in the print media. It first considers how debate quality in the context of a referendum campaign may best be conceptualized. It then uses content analysis of media coverage to investigate three aspects of that debate: its quantity; the balance between Yes and No arguments, and the quality of reason-giving. It finds that the quantity of debate was comparable to other recent electoral reform referendums. Coverage was predominantly, but not overwhelmingly, hostile to change. The different indicators of the quality of reason-giving present a mixed picture. The paper concludes by considering how the analysis could be extended through further comparison with other cases.
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When food processors have conjectures about rival firms' responses, their profit functions can be used to estimate the degree of market power in the food system. The effects of this power are investigated analytically and through applying the results to the U.S. pork sector
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A procedure is presented for comparing hypotheses about competition that makes no parametric assumptions about cost and demand functions, can be implemented with a modicum of data, and relies on Bayesian comparisons of non-nested hypotheses. The methodology is applied to data on five of the major U.S. food industries
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This article models the interactions between safety and quality control and stage of distribution in the food marketing complex
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Prediction mechanism is necessary for human visual motion to compensate a delay of sensory-motor system. In a previous study, “proactive control” was discussed as one example of predictive function of human beings, in which motion of hands preceded the virtual moving target in visual tracking experiments. To study the roles of the positional-error correction mechanism and the prediction mechanism, we carried out an intermittently-visual tracking experiment where a circular orbit is segmented into the target-visible regions and the target-invisible regions. Main results found in this research were following. A rhythmic component appeared in the tracer velocity when the target velocity was relatively high. The period of the rhythm in the brain obtained from environmental stimuli is shortened more than 10%. The shortening of the period of rhythm in the brain accelerates the hand motion as soon as the visual information is cut-off, and causes the precedence of hand motion to the target motion. Although the precedence of the hand in the blind region is reset by the environmental information when the target enters the visible region, the hand motion precedes the target in average when the predictive mechanism dominates the error-corrective mechanism.
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An investigation is presented of a quasi-stationary convective system (QSCS) which occurred over the UK Southwest Peninsula on 21 July 2010. This system was remarkably similar in its location and structure to one which caused devastating flash flooding in the coastal village of Boscastle, Cornwall on 16 August 2004. However, in the 2010 case rainfall accumulations were around four times smaller and no flooding was recorded. The more extreme nature of the Boscastle case is shown to be related to three factors: (1) higher rain rates, associated with a warmer and moister tropospheric column and deeper convective clouds; (2) a more stationary system, due to slower evolution of the large-scale flow; and (3) distribution of the heaviest precipitation over fewer river catchments. Overall, however, the synoptic setting of the two events was broadly similar, suggesting that such conditions favour the development of QSCSs over the Southwest Peninsula. A numerical simulation of the July 2010 event was performed using a 1.5-km grid length configuration of the Met Office Unified Model. This reveals that convection was repeatedly initiated through lifting of low-level air parcels along a quasi-stationary coastal convergence line. Sensitivity tests are used to show that this convergence line was a sea breeze front which temporarily stalled along the coastline due to the retarding influence of an offshore-directed background wind component. Several deficiencies are noted in the 1.5-km model’s representation of the storm system, including delayed convective initiation; however, significant improvements are observed when the grid length is reduced to 500 m. These result in part from an improved representation of the convergence line, which enhances the associated low-level ascent allowing air parcels to more readily reach their level of free convection. The implications of this finding for forecasting convective precipitation are discussed.
Resumo:
This paper investigates the application and use of development viability models in the formation of planning policies in the UK. Particular attention is paid to three key areas; the assumed development scheme in development viability models, the use of forecasts and the debate concerning Threshold Land Value. The empirical section reports on the results of an interview survey involving the main producers of development viability models and appraisals. It is concluded that, although development viability models have intrinsic limitations associated with model composition and input uncertainties, the most significant limitations are related to the ways that they have been adapted for use in the planning system. In addition, it is suggested that the contested nature of Threshold Land Value is an example of calculative practices providing a façade of technocratic rationality in the planning system.