612 research outputs found

    Hyperholomorpic connections on coherent sheaves and stability

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    Let MM be a hyperkaehler manifold, and FF a torsion-free and reflexive coherent sheaf on MM. Assume that FF (outside of its singularities) admits a connection with a curvature which is invariant under the standard SU(2)-action on 2-forms. If the curvature is square-integrable, then FF is stable and its singularities are hyperkaehler subvarieties in MM. Such sheaves (called hyperholomorphic sheaves) are well understood. In the present paper, we study sheaves admitting a connection with SU(2)-invariant curvature which is not necessarily square-integrable. This situation arises often, for instance, when one deals with higher direct images of holomorphic bundles. We show that such sheaves are stable.Comment: 37 pages, version 11, reference updated, corrected many minor errors and typos found by the refere

    The recent and rapid spread of Themeda triandra

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    Tropical savannas cover over 20% of land surface. They sustain a high diversity of mammalian herbivores and promote frequent fires, both of which are dependent on the underlying grass composition. These habitats are typically dominated by relatively few taxa, and the evolutionary origins of the dominant grass species are largely unknown. Here, we trace the origins of the genus Themeda, which contains a number of widespread grass species dominating tropical savannas. Complete chloroplast genomes were assembled for seven samples and supplemented with chloroplast and nuclear ITS markers for 71 samples representing 18 of the 27 Themeda species. Phylogenetic analysis supports a South Asian origin for both the genus and the widespread dominant T. triandra. This species emerged ~1.5 Ma from a group that had lived in the savannas of Asia for several million years. It migrated to Australia ~1.3 Ma and to mainland Africa ~0.5 Ma, where it rapidly spread in pre-existing savannas and displaced other species. Themeda quadrivalvis, the second most widespread Themeda species, is nested within T. triandra based on whole chloroplast genomes, and may represent a recent evolution of an annual growth form that is otherwise almost indistinguishable from T. triandra. The recent spread and modern-day dominance of T. triandra highlight the dynamism of tropical grassy biomes over millennial time-scales that has not been appreciated, with dramatic shifts in species dominance in recent evolutionary times. The ensuing species replacements likely had profound effects on fire and herbivore regimes across tropical savannas

    Hybrid manager-professionals' identity work : the maintenance and hybridization of medical professionalism in managerial contexts

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    We examine the ‘identity work’ of manager–professional ‘hybrids’, specifically medical professionals in managerial roles in the British National Health Service, to maintain and hybridize their professional identity and wider professionalism in organizational and policy contexts affected by managerialist ideas. Empirically, we differentiate between ‘incidental hybrids’, who represent and protect traditional institutionalized professionalism while temporarily in hybrid roles, and ‘willing hybrids’, who developed hybrid professional–managerial identities during formative identity work or later in reaction to potential professional identity violations. Questions about willing hybrids' professional identities led them to challenge and disrupt institutionalized professionalism, and use and integrate professionalism and managerialism, creating more legitimate hybrid professionalism in their managerial context. By aligning professionalism with their personal identity, and regulating and auditing other professionals, willing hybrids also position hybrids collectively as elite within their profession

    Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate

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    Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and to treat autoimmune diseases. MMF usage, however, is limited by severe gastrointestinal toxicity that is observed in approximately 45% of MMF recipients. The active form of the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation by bacterial beta-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within the gastrointestinal tract. GUS enzymes demonstrate distinct substrate preferences based on their structural features, and gut microbial GUS enzymes that reactivate MPA have not been identified. Here, we compare the fecal microbiomes of transplant recipients receiving MMF to healthy individuals using shotgun metagenomic sequencing. We find that neither microbial composition nor the presence of specific structural classes of GUS genes are sufficient to explain the differences in MPA reactivation measured between fecal samples from the two cohorts. We next employed a GUS-specific activity-based chemical probe and targeted metaproteomics to identify and quantify the GUS proteins present in the human fecal samples. The identification of specific GUS enzymes was improved by using the metagenomics data collected from the fecal samples. We found that the presence of GUS enzymes that bind the flavin mononucleotide (FMN) is significantly correlated with efficient MPA reactivation. Furthermore, structural analysis identified motifs unique to these FMN-binding GUS enzymes that provide molecular support for their ability to process this drug glucuronide. These results indicate that FMN-binding GUS enzymes may be responsible for reactivation of MPA and could be a driving force behind MPA-induced GI toxicity.Bio-organic Synthesi

    Efficacy of azithromycin in severe asthma from the AMAZES randomised trial

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    Background:Low-dose azithromycin is an effective therapy for persistent asthma; however, its benefit in severe asthma is not defined. Methods:Participants with severe asthma were identified from the AMAZES randomised, placebo-controlled trial of long-term (48 weeks) low-dose azithromycin. Participants who met one of the following severe asthma definitions were included: 1) Global Initiative for Asthma step 4 treatment with poor asthma control (asthma control questionnaire score ≥0.75); 2) International Severe Asthma Registry definition; 3) American Thoracic Society and European Respiratory Society severe asthma definitions. The rate of total exacerbations was calculated for each subgroup and efficacy of azithromycin compared with placebo. Asthma-related quality of life was assessed before and after treatment along with adverse effects. Results:Azithromycin significantly reduced asthma exacerbations in each group. In patients meeting the American Thoracic Society and European Respiratory Society task force definition of severe asthma (n=211), the rate of exacerbations with treatment was 1.2 per person-year, which was significantly less than for placebo (2.01 per person-year), giving an incidence rate ratio (95% CI) of 0.63 (0.41, 0.96). The proportion of participants experiencing at least one asthma exacerbation was reduced by azithromycin from 64% to 49% (p=0.021). A similar beneficial treatment effect was seen in participants poorly controlled with Global Initiative for Asthma step 4 treatment and those with International Severe Asthma Registry-defined severe asthma. Azithromycin also significantly improved the quality of life in severe asthma (p<0.05). Treatment was well tolerated, with gastrointestinal symptoms being the main adverse effect. Conclusion:Long-term, low-dose azithromycin reduced asthma exacerbations and improved the quality of life in patients with severe asthma, regardless of how this was defined. These data support the addition of azithromycin as a treatment option for patients with severe asthma.Peter G. Gibson, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James ... et al

    The credibility challenge for global fluvial flood risk analysis

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    Quantifying flood hazard is an essential component of resilience planning, emergency response, and mitigation, including insurance. Traditionally undertaken at catchment and national scales, recently, efforts have intensified to estimate flood risk globally to better allow consistent and equitable decision making. Global flood hazard models are now a practical reality, thanks to improvements in numerical algorithms, global datasets, computing power, and coupled modelling frameworks. Outputs of these models are vital for consistent quantification of global flood risk and in projecting the impacts of climate change. However, the urgency of these tasks means that outputs are being used as soon as they are made available and before such methods have been adequately tested. To address this, we compare multi-probability flood hazard maps for Africa from six global models and show wide variation in their flood hazard, economic loss and exposed population estimates, which has serious implications for model credibility. While there is around 30-40% agreement in flood extent, our results show that even at continental scales, there are significant differences in hazard magnitude and spatial pattern between models, notably in deltas, arid/semi-arid zones and wetlands. This study is an important step towards a better understanding of modelling global flood hazard, which is urgently required for both current risk and climate change projections

    The PHENIX Experiment at RHIC

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    The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix
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