173 research outputs found

    The uneven impact of recession on the voluntary and community sectors:Bristol and Liverpool

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    There has been much debate about the impact of recession and austerity on the voluntary and community sector over recent years. Using secondary data from the 2008 National Survey of Third Sector Organisations, Clifford et al. (2013), writing in this journal, have argued that voluntary sector organisations located in more deprived local authorities are likely to suffer most due to the combined effect of cuts in government funding in these areas and their greater dependency on statutory funding. This paper develops this argument by exploring the sector’s changing relationship with the state through an empirical analysis of the differential impact of recession and austerity on voluntary and community organisations involved in public service delivery in the two English core cities of Bristol and Liverpool. This paper highlights how the scale and unevenness of public spending cuts, the levels of voluntary sector dependency on statutory funding and the rising demands for the sector’s services in a period of recession and austerity are being experienced locally. It portrays a sector whose resilience is being severely tested and one that is being forced rapidly to restructure and reposition itself in an increasingly challenging funding environment. </jats:p

    Particle mesh simulations of the Lyman-alpha forest and the signature of Baryon Acoustic Oscillations in the intergalactic medium

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    We present a set of ultra-large particle-mesh simulations of the LyA forest targeted at understanding the imprint of baryon acoustic oscillations (BAO) in the inter-galactic medium. We use 9 dark matter only simulations which can, for the first time, simultaneously resolve the Jeans scale of the intergalactic gas while covering the large volumes required to adequately sample the acoustic feature. Mock absorption spectra are generated using the fluctuating Gunn-Peterson approximation which have approximately correct flux probability density functions (PDFs) and small-scale power spectra. On larger scales there is clear evidence in the redshift space correlation function for an acoustic feature, which matches a linear theory template with constant bias. These spectra, which we make publicly available, can be used to test pipelines, plan future experiments and model various physical effects. As an illustration we discuss the basic properties of the acoustic signal in the forest, the scaling of errors with noise and source number density, modified statistics to treat mean flux evolution and misestimation, and non-gravitational sources such as fluctuations in the photo-ionizing background and temperature fluctuations due to HeII reionization.Comment: 11 pages, 10 figures, minor changes to address referee repor

    Familial analysis of MMN in cannabis users: A case study

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    Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australi

    An investigation of mismatch negativity in current and ex-cannabis users using a feature controlled method

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    Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australi

    The Formation and Survival of Discs in a Lambda-CDM Universe

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    We study the formation of galaxies in a Lambda-CDM Universe using high resolution hydrodynamical simulations with a multiphase treatment of gas, cooling and feedback, focusing on the formation of discs. Our simulations follow eight haloes similar in mass to the Milky Way and extracted from a large cosmological simulation without restriction on spin parameter or merger history. This allows us to investigate how the final properties of the simulated galaxies correlate with the formation histories of their haloes. We find that, at z = 0, none of our galaxies contain a disc with more than 20 per cent of its total stellar mass. Four of the eight galaxies nevertheless have well-formed disc components, three have dominant spheroids and very small discs, and one is a spheroidal galaxy with no disc at all. The z = 0 spheroids are made of old stars, while discs are younger and formed from the inside-out. Neither the existence of a disc at z = 0 nor the final disc-to-total mass ratio seems to depend on the spin parameter of the halo. Discs are formed in haloes with spin parameters as low as 0.01 and as high as 0.05; galaxies with little or no disc component span the same range in spin parameter. Except for one of the simulated galaxies, all have significant discs at z > ~2, regardless of their z = 0 morphologies. Major mergers and instabilities which arise when accreting cold gas is misaligned with the stellar disc trigger a transfer of mass from the discs to the spheroids. In some cases, discs are destroyed, while in others, they survive or reform. This suggests that the survival probability of discs depends on the particular formation history of each galaxy. A realistic Lambda-CDM model will clearly require weaker star formation at high redshift and later disc assembly than occurs in our models.Comment: 14 pages, 10 figures, mn2e.cls. MNRAS in press, updated to match published versio

    Street CORNERS: Real-time Contextual Representation of Sensor Network Data for Environmental Trend Identification

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    Abstract-Sensor networks have been deployed for a range of rural and environmental applications. Wellregarded for the volume and range of data which can be obtained, wireless sensor network applications capable of using the data gathered have not been fully realized, particularly in urban settings. Street CORNERS is a wireless sensor network application which supports the contextual presentation of data gathered from an urban setting. The Street CORNERS application offers realtime data display, and provides support for predictive algorithms suitable for anticipating, detecting, and defending urban communities, among others, from environmental threats such as declining air quality and urban flash floods. Street CORNERS is presented in two parts. The network design and deployment is outlined, followed by a discussion of the design of the network application, which is involved in data preprocessing and the contextual presentation of the data gathered for trend identification

    Role of mitochondria-bound HK2 in rheumatoid arthritis fibroblast-like synoviocytes

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    BackgroundGlucose metabolism, specifically, hexokinase 2 (HK2), has a critical role in rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) phenotype. HK2 localizes not only in the cytosol but also in the mitochondria, where it protects mitochondria against stress. We hypothesize that mitochondria-bound HK2 is a key regulator of RA FLS phenotype.MethodsHK2 localization was evaluated by confocal microscopy after FLS stimulation. RA FLSs were infected with Green fluorescent protein (GFP), full-length (FL)-HK2, or HK2 lacking its mitochondrial binding motif (HK2ΔN) expressing adenovirus (Ad). RA FLS was also incubated with methyl jasmonate (MJ; 2.5 mM), tofacitinib (1 µM), or methotrexate (1 µM). RA FLS was tested for migration and invasion and gene expression. Gene associations with HK2 expression were identified by examining single-cell RNA sequencing (scRNA-seq) data from murine models of arthritis. Mice were injected with K/BxN serum and given MJ. Ad-FLHK2 or Ad-HK2ΔN was injected into the knee of wild-type mice.ResultsCobalt chloride (CoCl2) and platelet-derived growth factor (PDGF) stimulation induced HK2 mitochondrial translocation. Overexpression of the HK2 mutant and MJ incubation reversed the invasive and migrative phenotype induced by FL-HK2 after PDGF stimulation, and MJ also decreased the expression of C-X-C Motif Chemokine Ligand 1 (CXCL1) and Collagen Type I Alpha 1 Chain (COL1A1). Of interest, tofacitinib but not methotrexate had an effect on HK2 dissociation from the mitochondria. In murine models, MJ treatment significantly decreased arthritis severity, whereas HK2FL was able to induce synovial hypertrophy as opposed to HK2ΔN.ConclusionOur results suggest that mitochondrial HK2 regulates the aggressive phenotype of RA FLS. New therapeutic approaches to dissociate HK2 from mitochondria offer a safer approach than global glycolysis inhibition

    A subset of HLA-I peptides are not genomically templated: evidence for cis- and trans-spliced peptide ligands

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    The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy

    Fatal Human Infection with Rabies-related Duvenhage Virus, South Africa

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    Duvenhage virus was isolated from a patient who died of a rabieslike disease after being scratched by a bat early in 2006. This occurred ≈80 km from the site where the only other known human infection with the virus had occurred 36 years earlier
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