Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg^2.39, His^2.43 and Glu^3.46, which makes a polar lock with T^6.37. These alignments and models provide useful tools for understanding class B GPCR function.     

Mobilising community action towards a low-carbon future: Opportunities and challenges for local government in the UK

Over the last decade the important role that local authorities can play in catalyzing community action on climate change has been repeatedly emphasised by the UK Government. The paper examines this policy context and explores the options available to local authorities in terms of reaching and engaging their communities. The type of progressive response shown by some UK local authorities is illustrated with empirical evidence gathered through a study conducted in the London Borough of Islington focusing on their recently established ‘Green Living Centre’. The results confirm interest in this major council-led community initiative, with positive attitudes expressed by the majority of those questioned in terms of the advice and information available. However, it is also clear that many participants had preexisting pro-environmental attitudes and behavioural routines. Results from a broader sample of Islington residents indicate a substantial challenge in reaching the wider community, where enthusiasm for sustainability change and interest in this type of scheme were more mixed. The prospect for local government in addressing this challenge – and their ability to trigger and capitalize upon concepts of social change at the community level towards a lower carbon future – is discussed in the final part of the paper.     

Hydro,tidal and wave energy in Australia

The three renewable energy technologies discussed in this paper are based on water, but differ markedly in terms of the size of the available potential resource, the maturity of the associated conversion technologies, the extent to which they have been exploited to date, and the current research effort being devoted to their future development. Hydro-electricity and tidal power are both very mature technologies. The exploitation of Australia's relatively limited potential for hydro-electric development began over a century ago and the opportunities for further hydro-electric development are now very restricted. The country's significant tidal power resources, on the other hand, have not been exploited for electricity generation to date, but continual assessment of the feasibility of tidal power projects has been undertaken over the past half century. Although Australia has large ocean wave energy resources, ocean wave energy conversion technology is not yet fully commercial and no commercial wave generation plants are operating in Australia. A small number of wave energy conversion devices, however, are at the pilot testing stage.     

Organizational learning: conceptual challenges from a project perspective

Do-it-yourself (DIY) is a staple element of the spare time activities of many households, but little is known about the extent to which basic repair work is carried out through DIY and about the quality of this work. Through secondary analyses of UK government data (English House Condition Survey and Family Expenditure Survey), this paper examines the scale of DIY work by owner-occupiers, how work is organized, the interrelationship of DIY work, the use of unpaid help, and the use of contractors. It considers the types of work carried out, the characteristics of those who tackle DIY or use unpaid help, the dwelling types most likely to experience DIY work, and the motivations of and constraints on those home-owners who do it. The paper concludes with a discussion on the policy implications of these findings for government and the building industry. Although most DIY work is cosmetic and does not deal with basic repair and maintenance, the sheer scale of DIY ensures that it makes a contribution to improving housing conditions. The provision of more advice, information and education by government, local authorities and the private sector could ensure that more DIY work is of better quality and that home owners give priority to essential repairs whether or not they tackle these themselves.     

Detecting and ordering salient regions

We describe an ensemble approach to learning salient regions from arbitrarily partitioned data. The partitioning comes from the distributed processing requirements of large-scale simulations. The volume of the data is such that classifiers can train only on data local to a given partition. Since the data partition reflects the needs of the simulation, the class statistics can vary from partition to partition. Some classes will likely be missing from some or even most partitions. We combine a fast ensemble learning algorithm with scaled probabilistic majority voting in order to learn an accurate classifier from such data. Since some simulations are difficult to model without a considerable number of false positive errors, and since we are essentially building a search engine for simulation data, we order predicted regions to increase the likelihood that most of the top-ranked predictions are correct (salient). Results from simulation runs of a canister being torn and from a casing being dropped show that regions of interest are successfully identified in spite of the class imbalance in the individual training sets. Lift curve analysis shows that the use of data driven ordering methods provides a statistically significant improvement over the use of the default, natural time step ordering. Significant time is saved for the end user by allowing an improved focus on areas of interest without the need to conventionally search all of the data.     

阿瑞娜大舞台演艺中心:对城市来说这既是辉煌又是一大挑战

当你在华盛顿海滨的1-395遭遇堵车时,向东面看会发现地平线上的一座建筑。由Bing Thom建筑事务所孟令强设计的阿瑞娜大舞台演艺中心的白色屋顶清晰可见,它与华盛顿市区西南部混乱的景观一样高,但比周围的建筑更具幽默感和诗意。站在街上或从海滨地铁站出来都能看到它大面积的玻璃幕墙、木头支柱和闪烁的、云一般的白色屋顶。     

Spatially resolved positron annihilation spectroscopy on friction stir weld induced defects

A friction stir welded (FSW) Al alloy sample was investigated by Doppler broadening spectroscopy (DBS) of the positron annihilation line. The spatially resolved defect distribution showed that the material in the joint zone becomes completely annealed during the welding process at the shoulder of the FSW tool, whereas at the tip, annealing is prevailed by the deterioration of the material due to the tool movement. This might be responsible for the increased probability of cracking in the heat affected zone of friction stir welds. Examination of a material pairing of steel S235 and the Al alloy Silafont36 by coincident Doppler broadening spectroscopy (CDBS) indicates the formation of annealed steel clusters in the Al alloy component of the sample. The clear visibility of Fe in the CDB spectra is explained by the very efficient trapping at the interface between steel cluster and bulk.     

Systemic inflammatory load in humans is suppressed by consumption of two formulations of dried,encapsulated juice concentrate

Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease, diabetes, and cancer. A high “inflammatory load” is defined as elevated inflammation markers in blood or other tissues. We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders (FVB) or without (FV) could impact markers of inflammatory load. Using a double‐blind, placebo‐controlled approach, 117 subjects were randomly assigned to receive placebo, FV, or FVB capsules. Blood was drawn at baseline and after 60 d of capsule consumption. We measured inflammatory markers (high sensitivity C‐Reactive Protein, Monocyte Chemotactic Protein‐1, Macrophage Inflammatory Protein 1‐β, and Regulated upon Activation, Normal T cell Expressed and Secreted), superoxide dismutase, and micronutrients (β‐carotene, vitamin C, and vitamin E). Results showed Monocyte Chemotactic Protein‐1, Macrophage Inflammatory Protein 1‐β, and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB, relative to placebo. Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti‐inflammatory properties.     

Contribution of combined sewer overflows to trace contaminant loads in urban streams

The present study examines the contribution of combined sewer overflows (CSO) to loads and concentrations of trace contaminants in receiving surface water. A simple method to assess the ratio of CSO to wastewater treatment plant (WWTP) effluents was applied to the urban River Spree in Berlin, Germany. The assessment indicated that annual loads are dominated by CSO for substances with removal in WWTP above ∼95%. Moreover, it showed that substances with high removal in WWTP can lead to concentration peaks in the river during CSO events. The calculated results could be verified based on eight years of monitoring data from the River Spree, collected between 2000 and 2007. Substances that are well removed in WWTP such as NTA (nitrilotriacetic acid) were found to occur in significantly increased concentration during CSO, while the concentration of substances that are poorly removable in WWTP such as EDTA (ethylenediaminetetraacetic acid) decreased in CSO-influenced samples due to dilution effects. The overall results indicate the potential importance of the CSO pathway of well-removable sewage-based trace contaminants to rivers. In particular, high concentrations during CSO events may be relevant for aquatic organisms. Given the results, it is suggested to include well-removable, sewage-based trace contaminants, a substance group often neglected in the past, in future studies on urban rivers in case of combined sewer systems. The presented methodology is suggested for a first assessment, since it is based solely on urban drainage data, which is available in most cities.