984 resultados para Héloïse, 1101-1164


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Local Agenda 21 seeks the meaningful involvement of a wide range of local groups and stakeholders in the formulation and implementation of public policy and a free flow of communication and discussion between them and their respective local authorities (and other areas and levels of decision-making). This paper explores the reality of this process using case study evidence from local planning practice in Liverpool (in the north of England) and Reading (in the south of the country). It concentrates on the interaction between LA21 groups and local planning authorities around the preparation of local land use plans and other policy initiatives and the day-to-day regulation of development permits. The paper builds on ‘New Institutionalist’ theory to explore the constraints and opportunities for significant transformations in social, political and economic ‘structures’ or ‘ways of doing things’ through the LA21 process. It concludes that the two cases provide evidence of mixed success in achieving such changes in established planning practices.

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Many numerical models for weather prediction and climate studies are run at resolutions that are too coarse to resolve convection explicitly, but too fine to justify the local equilibrium assumed by conventional convective parameterizations. The Plant-Craig (PC) stochastic convective parameterization scheme, developed in this paper, solves this problem by removing the assumption that a given grid-scale situation must always produce the same sub-grid-scale convective response. Instead, for each timestep and gridpoint, one of the many possible convective responses consistent with the large-scale situation is randomly selected. The scheme requires as input the large-scale state as opposed to the instantaneous grid-scale state, but must nonetheless be able to account for genuine variations in the largescale situation. Here we investigate the behaviour of the PC scheme in three-dimensional simulations of radiative-convective equilibrium, demonstrating in particular that the necessary space-time averaging required to produce a good representation of the input large-scale state is not in conflict with the requirement to capture large-scale variations. The resulting equilibrium profiles agree well with those obtained from established deterministic schemes, and with corresponding cloud-resolving model simulations. Unlike the conventional schemes the statistics for mass flux and rainfall variability from the PC scheme also agree well with relevant theory and vary appropriately with spatial scale. The scheme is further shown to adapt automatically to changes in grid length and in forcing strength.

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RATIONALE: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively. OBJECTIVES: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease. METHODS: We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS: Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells. CONCLUSIONS: Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.

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Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of Na(V)1.5 and to induction of the late Na(+) current. We also show that the antianginal drug ranolazine can abolish CO-induced early after-depolarizations, highlighting a novel approach to the treatment of CO-induced arrhythmias.

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Direct electrochemical templating is carried out using a thin layer of a self-assembled diamond phase (QIID) of phytantriol to create a platinum film with a novel nanostructure. Small-angle X-ray scattering shows that the nanostructured platinum films are asymmetrically templated and exhibit “single diamond” morphology with Fd3m symmetry.

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Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

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Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 (PAR2) to induce alterations in contraction of airway smooth muscle that have been implicated in asthma in experimental animals. Although tryptase inhibitors are under development for treatment of asthma, little is known about the localization and function of PAR2 in human airways. We detected PAR2 expression in primary cultures of human airway smooth muscle cells using reverse transcriptase/polymerase chain reaction (RT-PCR) and immunofluorescence. The PAR2 agonists trypsin, tryptase, and an activating peptide (SLIGKV-NH2) stimulated calcium mobilization in these cells. PAR2 agonists strongly desensitized responses to a second challenge of trypsin and SLIGKV-NH2, but not to thrombin, indicating that they activate a receptor distinct from the thrombin receptors. Immunoreactive PAR2 was detected in smooth muscle, epithelium, glands, and endothelium of human bronchi. Trypsin, SLIGKV-NH2, and tryptase stimulated contraction of isolated human bronchi. Contraction was increased by removal of the epithelium and diminished by indomethacin. Thus, PAR2 is expressed by human bronchial smooth muscle where its activation mobilizes intracellular Ca2+ and induces contraction. These results are consistent with the hypothesis that PAR2 agonists, including tryptase, induce bronchoconstriction of human airway by stimulating smooth muscle contraction. PAR2 antagonists may be useful drugs to prevent bronchoconstriction.

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Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9), Met(O2)(11)]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.

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The protease activated receptor-2 (PAR-2) belongs to a family of G-protein-coupled receptors that are activated by proteolysis. Trypsin cleaves PAR-2, exposing an N-terminal tethered ligand (SLIGRL) that activates the receptor. Messenger RNA (mRNA) for PAR-2 was found in guinea pig airway tissue by reverse transcription-polymerase chain reaction, and PAR-2 was found by immunohistochemistry in airway epithelial and smooth-muscle cells. In anesthetized guinea pigs, trypsin and SLIGRL-NH(2) (given intratracheally or intravenously) caused a bronchoconstriction that was inhibited by the combination of tachykinin-NK(1) and -NK(2) receptor antagonists and was potentiated by inhibition of nitric oxide synthase (NOS). Trypsin and SLIGRL-NH(2) relaxed isolated trachea and main bronchi, and contracted intrapulmonary bronchi. Relaxation of main bronchi was abolished or reversed to contraction by removal of epithelium, administration of indomethacin, and NOS inhibition. PAR-1, PAR-3, and PAR-4 were not involved in the bronchomotor action of either trypsin or SLIGRL-NH(2), because ligands of these receptors were inactive either in vitro or in vivo, and because thrombin (a PAR-1 and PAR-3 agonist) did not show cross-desensitization with PAR-2 agonists in vivo. Thus, we have localized PAR-2 to the guinea-pig airways, and have shown that activation of PAR-2 causes multiple motor effects in these airways, including in vivo bronchoconstriction, which is in part mediated by a neural mechanism.

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Quasi-stationary convective bands can cause large localised rainfall accumulations and are often anchored by topographic features. Here, the predictability of and mechanisms causing one such band are determined using ensembles of the Met Office Unified Model at convection-permitting resolution (1.5 km grid length). The band was stationary over the UK for 3 h and produced rainfall accumulations of up to 34 mm. The amount and location of the predicted rainfall was highly variable despite only small differences between the large-scale conditions of the ensemble members. Only three of 21 members of the control ensemble produced a stationary rain band; these three had the weakest upstream winds and hence lowest Froude number. Band formation was due to the superposition of two processes: lee-side convergence resulting from flow around an upstream obstacle and thermally forced convergence resulting from elevated heating over the upstream terrain. Both mechanisms were enhanced when the Froude number was lower. By increasing the terrain height (thus reducing the Froude number), the band became more predictable. An ensemble approach is required to successfully predict the possible occurrence of such quasi-stationary convective events because the rainfall variability is largely modulated by small variations of the large-scale flow. However, high-resolution models are required to accurately resolve the small-scale interactions of the flow with the topography upon which the band formation depends. Thus, although topography provides some predictability, the quasi-stationary convective bands anchored by it are likely to remain a forecasting challenge for many years to come.

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The UK new-build housing sector is facing dual pressures to expand supply, whilst delivering against tougher planning and Building Regulation requirements; predominantly in the areas of sustainability. The sector is currently responding by significantly scaling up production and incorporating new technical solutions into new homes. This trajectory of up-scaling and technical innovation has been of research interest; but this research has primarily focus on the ‘upstream’ implications for house builders’ business models and standardised design templates. There has been little attention, though, to the potential ‘downstream’ implications of the ramping up of supply and the introduction of new technologies for build quality and defects. This paper contributes to our understanding of the ‘downstream’ implications through a synthesis of the current UK defect literature with respect to new-build housing. It is found that the prevailing emphasis in the literature is limited to the responsibility, pathology and statistical analysis of defects (and failures). The literature does not extend to how house builders individually and collectively, in practice, collect and learn from defects information. The paper concludes by describing an ongoing collaborative research programme with the National House Building Council (NHBC) to: (a) understand house builders’ localised defects analysis procedures, and their current knowledge feedback loops to inform risk management strategies; and, (b) building on this understanding, design and test action research interventions to develop new data capture, learning processes and systems to reduce targeted defects.

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We assess how effectively the current network of protected areas (PAs) across the Iberian Peninsula will conserve plant diversity under near-future (2020) climate change. We computed 3267 MAXENT environmental niche models (ENMs) at 1-km spatial resolution for known Iberian plant species under two climate scenarios (1950-2000 baseline & 2020). To predict near-future species distributions across the network of Iberian and Balearics PAs, we combined projections of species’ ENMs with simulations of propagule dispersal by using six scenarios of annual dispersal rates (no dispersal, 0.1 km, 0.5 km, 1 km, 2 km and unlimited). Mined PA grid cell values for each species were then analyzed. We forecast 3% overall floristic diversity richness loss by 2020. The habitat of regionally extant species will contract on average by 13.14%. Niche movement exceeds 1 km per annum for 30% of extant species. While the southerly range margin of northern plant species retracts northward at 8.9 km per decade, overall niche movement is more easterly and westerly than northerly. There is little expansion of the northern range margin of southern plant species even under unlimited dispersal. Regardless of propagule dispersal rate, altitudinal niche movement of +25 m per decade is strongest for northern species. Pyrenees flora is most vulnerable to near-future climate change with many northern plant species responding by shifting their range westerly and easterly rather than northerly. Northern humid habitats will be particularly vulnerable to near-future climate change. Andalusian National Parks will become important southern biodiversity refuges. With limited human intervention (particularly in the Pyrenees), we conclude that floristic diversity in Iberian PAs should withstand near-future climate change.

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The date of the Late Bronze Age Minoan eruption of the Thera volcano has provoked much debate among archaeologists, not least in a recent issue of Antiquity (‘Bronze Age catastrophe and modern controversy: dating the Santorini eruption’, March 2014). Here, the authors respond to those recent contributions, citing evidence that closes the gap between the conclusions offered by previous typological, stratigraphic and radiometric dating techniques. They reject the need to choose between alternative approaches to the problem and make a case for the synchronisation of eastern Mediterranean and Egyptian chronologies with agreement on a ‘high’ date in the late seventeenth century BC for the Thera eruption.

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Holm oak (Quercus ilex), a widespread urban street tree in the Mediterranean region, is widely used as biomonitor of persistent atmospheric pollutants, especially particulate-bound metals. By using lab- and field-based experimental approaches, we compared the leaf-level capacity for particles’ capture and retention between Q. ilex and other common Mediterranean urban trees: Quercus cerris, Platanus × hispanica, Tilia cordata and Olea europaea. All applied methods were effective in quantifying particulate capture and retention, although not univocal in ranking species performances. Distinctive morphological features of leaves led to differences in species’ ability to trap and retain particles of different size classes and to accumulate metals after exposure to traffic in an urban street. Overall, P. × hispanica and T. cordata showed the largest capture potential per unit leaf area for most model particles (Na+ and powder particles), and street-level Cu and Pb, while Q. ilex acted intermediately. After wash-off experiments, P. × hispanica leaves had the greatest retention capacity among the tested species and O. europaea the lowest. We concluded that the Platanus planting could be considered in Mediterranean urban environments due to its efficiency in accumulating and retaining airborne particulates; however, with atmospheric pollution being typically higher in winter, the evergreen Q. ilex represents a better year-round choice to mitigate the impact of airborne particulate pollutants.