94 resultados para Elster, Jon
Resumo:
As low carbon technologies become more pervasive, distribution network operators are looking to support the expected changes in the demands on the low voltage networks through the smarter control of storage devices. Accurate forecasts of demand at the single household-level, or of small aggregations of households, can improve the peak demand reduction brought about through such devices by helping to plan the appropriate charging and discharging cycles. However, before such methods can be developed, validation measures are required which can assess the accuracy and usefulness of forecasts of volatile and noisy household-level demand. In this paper we introduce a new forecast verification error measure that reduces the so called “double penalty” effect, incurred by forecasts whose features are displaced in space or time, compared to traditional point-wise metrics, such as Mean Absolute Error and p-norms in general. The measure that we propose is based on finding a restricted permutation of the original forecast that minimises the point wise error, according to a given metric. We illustrate the advantages of our error measure using half-hourly domestic household electrical energy usage data recorded by smart meters and discuss the effect of the permutation restriction.
Resumo:
During the 1990s there was a major change in the state of the world's oceans. In particular, the North Atlantic underwent a rapid warming, with sea surface temperatures (SSTs) in the subpolar gyre region increasing by 1°C in just a few years. Associated with the changes in SST patterns were changes in the surface climate, in particular, a tendency for warm and dry conditions over areas of North America in all seasons, and warm springs and wet summers over areas of Europe. Here, the extent to which a climate prediction system initialized using observations of the ocean state is able to capture the observed changes in seasonal mean surface climate is investigated. Rather than examining predictions of the mid-1990s North Atlantic warming event itself, this study compares hindcasts started before and after the warming, relative to hindcasts that do not assimilate information. It is demonstrated that the hindcasts capture many aspects of the observed changes in seasonal mean surface climate, especially in North, South, and Central America and in Europe. Furthermore, the prediction system retains skill beyond the first year. Finally, it is shown that, in addition to memory of Atlantic SSTs, successfully predicting Pacific SSTs was likely important for the hindcasts to predict surface climate over North America.
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Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment for coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Since several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1, we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signalling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1-/- platelets. Activation of PECAM-1 signalling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3-K) and diminished PI3-K signalling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provides evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs.
Resumo:
OBJECTIVE: Dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. In this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. APPROACH AND RESULTS: Tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. It inhibited agonist-induced integrin αIIbβ3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. Tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. Further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cGMP levels in platelets, although phosphodiesterase activity was unaffected. Consistent with increased cGMP levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at S239. CONCLUSIONS: This study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease.
Resumo:
Global ocean circulation is an important factor in climate variability and change. In particular, changes in the strength of the Atlantic meridional overturning circulation (AMOC) have been implicated in ancient climate events, as well as in recent climate anomalies such as the rapid warming of the North Atlantic Ocean in the mid-1990s. A series of moored current meters and temperature sensors deployed in the Atlantic at 26° N known as the RAPID-MOCHA array has been used to monitor the strength of meridional overturning since 2004. The data indicate a decline in this strength over the period 2004–20123. Here, using additional observations and climate model simulations we suggest that this measured decline is not merely a short-term fluctuation, but is part of a substantial reduction in meridional overturning occurring on a decadal timescale.
Resumo:
Epidemiological and clinical trials reveal compelling evidence for the ability of dietary flavonoids to lower cardiovascular disease risk. The mechanisms of action of these polyphenolic compounds are diverse, and of particular interest is their ability to function as protein and lipid kinase inhibitors. We have previously described structure-activity studies that reinforce the possibility for using flavonoid structures as templates for drug design. In the present study, we aim to begin constructing rational screening strategies for exploiting these compounds as templates for the design of clinically relevant, antiplatelet agents. We used the platelet as a model system to dissect the structural influence of flavonoids, stilbenes, anthocyanidins, and phenolic acids on inhibition of cell signaling and function. Functional groups identified as relevant for potent inhibition of platelet function included at least 2 benzene rings, a hydroxylated B ring, a planar C ring, a C ring ketone group, and a C-2 positioned B ring. Hydroxylation of the B ring with either a catechol group or a single C-4' hydroxyl may be required for efficient inhibition of collagen-stimulated tyrosine phosphorylated proteins of 125 to 130 kDa, but may not be necessary for that of phosphotyrosine proteins at approximately 29 kDa. The removal of the C ring C-3 hydroxyl together with a hydroxylated B ring (apigenin) may confer selectivity for 37 to 38 kDa phosphotyrosine proteins. We conclude that this study may form the basis for construction of maps of flavonoid inhibitory activity on kinase targets that may allow a multitargeted therapeutic approach with analogue counterparts and parent compounds.
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The main purpose of the work described in this paper is to examine the extent to which the L2 developmental changes predicted by Kroll and Stewart's (1994) Revised Hierarchical Model (RHM) can be understood by word association response behaviour. The RHM attempts to account for the relative “strength of the links between words and concepts in each of the bilingual's languages” (Kroll, Van Hell, Tokowicz & Green, 2010, p. 373). It proposes that bilinguals with higher L2 proficiency tend to rely less on mediation, while less proficient L2 learners tend to rely on mediation and access L2 words by translating from L1 equivalents. In this paper, I present findings from a simple word association task. More proficient learners provided a greater proportion of collocational links, suggesting that they mediate less when compared to less proficient learners. The results provide tentative support for Kroll and Stewart's model
Resumo:
In the 1960s North Atlantic sea surface temperatures (SST) cooled rapidly. The magnitude of the cooling was largest in the North Atlantic subpolar gyre (SPG), and was coincident with a rapid freshening of the SPG. Here we analyze hindcasts of the 1960s North Atlantic cooling made with the UK Met Office’s decadal prediction system (DePreSys), which is initialised using observations. It is shown that DePreSys captures—with a lead time of several years—the observed cooling and freshening of the North Atlantic SPG. DePreSys also captures changes in SST over the wider North Atlantic and surface climate impacts over the wider region, such as changes in atmospheric circulation in winter and sea ice extent. We show that initialisation of an anomalously weak Atlantic Meridional Overturning Circulation (AMOC), and hence weak northward heat transport, is crucial for DePreSys to predict the magnitude of the observed cooling. Such an anomalously weak AMOC is not captured when ocean observations are not assimilated (i.e. it is not a forced response in this model). The freshening of the SPG is also dominated by ocean salt transport changes in DePreSys; in particular, the simulation of advective freshwater anomalies analogous to the Great Salinity Anomaly were key. Therefore, DePreSys suggests that ocean dynamics played an important role in the cooling of the North Atlantic in the 1960s, and that this event was predictable.
Resumo:
The central sector of the last British–Irish Ice Sheet (BIIS) was characterised by considerable complexity, both in terms of its glacial stratigraphy and geomorphological signature. This complexity is reflected by the large number and long history of papers that have attempted to decipher the glaciodynamic history of the region. Despite significant advances in our understanding, reconstructions remain hotly debated and relatively local, thereby hindering attempts to piece together BIIS dynamics. This paper seeks to address these issues by reviewing geomorphological mapping evidence of palimpsest flow signatures and providing an up-to-date stratigraphy of the region. Reconciling geomorphological and sedimentological evidence with relative and absolute dating constraints has allowed us to develop a new six-stage glacial model of ice-flow history and behaviour in the central sector of the last BIIS, with three major phases of glacial advance. This includes: I. Eastwards ice flow through prominent topographic corridors of the north Pennines; II. Cessation of the Stainmore ice flow pathway and northwards migration of the North Irish Sea Basin ice divide; III. Stagnation and retreat of the Tyne Gap Ice Stream; IV. Blackhall Wood–Gosforth Oscillation; V. Deglaciation of the Solway Lowlands; and VI. Scottish Re-advance and subsequent final retreat of ice out of the central sector of the last BIIS. The ice sheet was characterised by considerable dynamism, with flow switches, initiation (and termination) of ice streams, draw-down of ice into marine ice streams, repeated ice-marginal fluctuations and the production of large volumes of meltwater, locally impounded to form ice-dammed glacial lakes. Significantly, we tie this reconstruction to work carried out and models developed for the entire ice sheet. This therefore situates research in the central sector within contemporary understanding of how the last BIIS evolved over time.
Resumo:
As weather and climate models move toward higher resolution, there is growing excitement about potential future improvements in the understanding and prediction of atmospheric convection and its interaction with larger-scale phenomena. A meeting in January 2013 in Dartington, Devon was convened to address the best way to maximise these improvements, specifically in a UK context but with international relevance. Specific recommendations included increased convective-scale observations, high-resolution virtual laboratories, and a system of parameterization test beds with a range of complexities. The main recommendation was to facilitate the development of physically based convective parameterizations that are scale-aware, non-local, non-equilibrium, and stochastic.