Low carbon housing: lessons from Elm Tree Mews

This report sets out the findings from a low carbon housing trial at Elm Tree Mews, York, and discusses the technical and policy issues that arise from it. The Government has set an ambitious target for all new housing to be zero carbon by 2016. With the application of good insulation, improved efficiencies and renewable energy, this is theoretically possible. However, there is growing concern that, in practice, even existing carbon standards are not being achieved and that this performance gap has the potential to undermine zero carbon housing policy. The report seeks to address these concerns through the detailed evaluation of a low carbon development at Elm Tree Mews. The report: * evaluates the energy/carbon performance of the dwellings prior to occupation and in use; * analyses the procurement, design and construction processes that give rise to the performance achieved; * explores the resident experience; * draws out lessons for the development of zero carbon housing and the implications for government policy; and * proposes a programme for change, designed to close the performance gap

Crystallization and preliminary X-ray analysis of the sporulation factor SpoIIAA in its native and phosphorylated forms

Sporulation in Bacillus begins with an asymmetric cell division producing two progeny with identical chromosomes but different developmental fates. As such, it is a simple example of cellular differentiation. The establishment of cell type is controlled by a series of alternate RNA polymerase sigma subunits. The first compartment-specific sigma factor is sigma (F), whose activity is controlled by SpoIIAB, an anti-sigma factor, and SpoIIAA, an anti-sigma factor antagonist which is phosphorylated by the kinase activity of SpoIIAB. Here, the preliminary crystallographic analysis of SpoIIAA and phosphorylated SpoIIAA from B. sphaericus in forms suitable for high-resolution structure determination are reported

Transcription activator structure reveals redox control of a replication initiation reaction†

Redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. Proteins regulated through redox-sensitive cysteines have been characterized but specific ‘sulphydryl switches’ in replication proteins remain to be identified. In bovine papillomavirus type-1, DNA replication begins when the viral transcription factor E2 recruits the viral initiator protein E1 to the origin of DNA replication (ori). Here we show that a novel dimerization interface in the E2 transcription activation domain is stabilized by a disulphide bond. Oxidative cross-linking via Cys57 sequesters the interaction surface between E1 and E2, preventing pre-initiation and replication initiation complex formation. Our data demonstrate that as well as a mechanism for regulating DNA binding, redox reactions can control replication by modulating the tertiary structure of critical protein factors using a specific redox sensor

Activation of the damage-associated molecular pattern receptor P2X7 induces interleukin-1B release from canine monocytes

P2X7, a damage-associated molecular pattern receptor and adenosine 5\u27-triphosphate (ATP)-gated cation channel, plays an important role in the activation of the NALP3 inflammasome and subsequent release of interleukin (IL)-1β from human monocytes; however its role in monocytes from other species including the dog remains poorly defined. This study investigated the role of P2X7 in canine monocytes, including its role in IL-1β release. A fixed-time flow cytometric assay demonstrated that activation of P2X7 by extracellular ATP induces the uptake of the organic cation, YO-PRO-12+, into peripheral blood monocytes from various dog breeds, a process impaired by the specific P2X7 antagonist, A438079. Moreover, in five different breeds, relative P2X7 function in monocytes was about half that of peripheral blood T cells but similar to that of peripheral blood B cells. Reverse transcription-PCR demonstrated the presence of P2X7, NALP3, caspase-1 and IL-1β in LPSprimed canine monocytes. Immunoblotting confirmed the presence of P2X7 in LPS-primed canine monocytes. Finally, extracellular ATP induced YO-PRO-12+ uptake into and IL-1β release from these cells, with both processes impaired by A438079. These results demonstrate that P2X7 activation induces the uptake of organic cations into and the release of IL-1β from canine monocytes. These findings indicate that P2X7 may play an important role in IL-1β-dependent processes in dogs

R270C polymorphism leads to loss of function of the canine P2X7 receptor

The relative function of the P2X7 receptor, an ATP-gated ion channel, varies between humans due to polymorphisms in the P2RX7 gene. This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relative function of P2X7 on monocytes varied between individual dogs. The canine P2RX7 gene encoded four missense polymorphisms: F103L and P452S, found in heterozygous and homozygous dosage, and R270C and R365Q, found only in heterozygous dosage. Moreover, R270C and R365Q were associated with the cocker spaniel and Labrador retriever, respectively. F103L, R270C, and R365Q but not P452S corresponded to decreased P2X7 function in monocytes but did not explain the majority of differences in P2X7 function between dogs, indicating that other factors contribute to this variability. Heterologous expression of site-directed mutants of P2X7 in human embryonic kidney-293 cells indicated that the R270C mutant was nonfunctional, the F103L and R365Q mutants had partly reduced function, and the P452S mutant functioned normally. Taken together, these data highlight that a R270C polymorphism has major functional impact on canine P2X7

Partner (dis)agreement on moving desires and the subsequent moving behaviour of couples

Residential mobility decisions are known to be made at the household level. However, most empirical analyses of residential mobility relate moving behaviour to the housing and neighbourhood satisfaction and pre-move thoughts of individuals. If partners in a couple do not share evaluations of dwelling or neighbourhood quality or do not agree on whether moving is (un)desirable, ignoring these disagreements will lead to an inaccurate assessment of the strength of the links between moving desires and actual moves. This study is one of the first to investigate disagreements in moving desires between partners and the subsequent consequences of such disagreements for moving behaviour. Drawing on British Household Panel Survey (BHPS) data, we find that disagreement about the desirability of moving is most likely where partners also disagree about the quality of their dwelling or neighbourhood. Panel logistic regression models show that the moving desires of both partners interact to affect the moving behaviour of couples. Only 7.6% of couples move if only the man desires to move, whereas 20.1% of shared moving desires lead to a subsequent move.This is the pre-peer reviewed version of the following article: Coulter, R., van Ham, M. and Feijten, P. 2012. Partner (dis)agreement on moving desires and the subsequent moving behaviour of couples. Population, Space and Place 18(1), pp. 16-30, which has been published in final form at http://dx.doi.org/10.1002/psp.700

Pharmacological and genetic characterisation of the canine P2X4 receptor

Background and Purpose: P2X4 receptors are emerging therapeutic targets for treating chronic pain and cardiovascular disease. Dogs are well-recognised natural models of human disease, but information regarding P2X4 receptors in dogs is lacking. To aid the development and validation of P2X4 receptor ligands, we have characterised and compared canine and human P2X4 receptors. Experimental Approach: Genomic DNA was extracted from whole blood samples from 101 randomly selected dogs and sequenced across the P2RX4 gene to identify potential missense variants. Recombinant canine and human P2X4 receptors tagged with Emerald GFP were expressed in 1321N1 and HEK293 cells and analysed by immunoblotting and confocal microscopy. In these cells, receptor pharmacology was characterised using nucleotide-induced Fura-2 AM measurements of intracellular Ca 2+ and known P2X4 receptor antagonists. P2X4 receptor-mediated inward currents in HEK293 cells were assessed by automated patch clamp. Key Results: No P2RX4 missense variants were identified in any canine samples. Canine and human P2X4 receptors were localised primarily to lysosomal compartments. ATP was the primary agonist of canine P2X4 receptors with near identical efficacy and potency at human receptors. 2′(3′)-O-(4-benzoylbenzoyl)-ATP, but not ADP, was a partial agonist with reduced potency for canine P2X4 receptors compared to the human orthologues. Five antagonists inhibited canine P2X4 receptors, with 1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea displaying reduced sensitivity and potency at canine P2X4 receptors. Conclusion and Implications: P2X4 receptors are highly conserved across dog pedigrees and display expression patterns and pharmacological profiles similar to human receptors, supporting validation and use of therapeutic agents for P2X4 receptor-related disease onset and management in dogs and humans

Air Freight

This study highlights the supplier selection process: identifying the vendors, requesting formal bids, evaluating bids submitted via a weighted metric process, and ultimately setting contract terms and negotiating details of the logistics process.https://corescholar.libraries.wright.edu/ms_lscm/1021/thumbnail.jp

IN-SITU MONITORING OF THE SELECTIVE LASER MELTING PROCESS VIA OPTICAL TOMOGRAPHY

Selective laser melting (SLM) is a method of additive manufacturing that has become increasingly popular in recent years for fabricating complex components, especially in the medical and aerospace industries. By fabricating components in a layerwise fashion, SLM provides users the freedom to design components based on their desired functionality rather than their manufacturability. The current state-of-the-art for SLM is limited though, as defects induced by the SLM process have proven to greatly alter the material properties of fabricated parts. In addition, traditional post-process nondestructive inspection methods have experienced significant difficulty in accurately detecting these process-induced defects. Therefore, the objective of this study is to investigate methods of processing and analysis for optical in-situ monitoring data recorded during SLM fabrication of six test samples. Four of the samples were designed with seeded (i.e., intentional) defects located at their center to serve as a reference defect signatures in the resulting in-situ data. An off-axis optical tomography (OT) sensor was used to capture near-infrared (NIR) melt pool emissions during the fabrication of each layer. Image analysis was subsequently performed using a custom squared difference (SD) operator to enhance defect signatures in the OT data. Results from the SD operator were then used to perform k-means clustering to partition the data into k relevant clusters, where the optimal number of k clusters for each image is employed as metric for detecting the onset of defects in the samples. By employing OT image data from samples containing seeded intentional defects, the k-means clustering approach was investigated as a method of defect detection for the in-situ OT images. Results showed that the SD operator is capable of elucidating anomalous signatures in the in-situ data. However, variations within the SD distributions ultimately limited detection capabilities as the output from k-means clustering was unable to accurately distinguish the seeded defects from the fused regions of material