77 research outputs found

    Four Dimensional Superconformal Field Theories From String Theory.

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    PhDIn this work, we discuss four dimensional SCFTs which descend from string theory and M-theory. These SCFTs arise naturally from stacks of string and M- theory branes and are useful tools for studying various phenomena in four dimensional quantum eld theory. In the rst chapter we give a brief non-technical introduction and historical background to string theory and supersymmetry which motivates the study of these elds. The second chapter contains a review of background material related to supersymmetric gauge theories and conformal eld theories. In this context, we discuss anomalies and moduli spaces, and their utility in quantum eld theory. Additionally, we introduce how to construct some exotic eld theories by coupling non-Lagrangian sectors to Lagrangian theories. In the third chapter, we examine a special family of four dimensional N = 2 SCFTs that are obtained by wrapping the six dimensional (2; 0) theory on a Riemann surface. We derive some properties of these theories and discover various dualities involving them. We then give a brief introduction to the superconformal index and use it to examine the operator content of these theories. Finally we construct new N = 1 gauge theories by coupling these N = 2 theories to N = 1 matter and examining the resulting RG ows. In the fourth chapter, we discuss the problem of counting chiral primary gaugeinvariant operators in D-brane world-volume gauge theories. These theories live on a at stack of D3-branes with various transverse toric geometries. We investigate the six dimensional transverse space, as well as the moduli space and chiral ring of the world-volume theory, and nd previously unknown relationships between these elementsQueen Mary University of London Centre for Research in String Theor

    Epidemiology of Urban Canine Rabies, Santa Cruz, Bolivia, 1972ā€“1997

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    We analyzed laboratory data from 1972 to 1997 from Santa Cruz, Bolivia, to determine risk factors for laboratory canine samplesā€™ testing positive for Rabies virus (RABV). Of 9,803 samples, 50.7% tested positive for RABV; the number of cases and the percentage positive has dropped significantly since 1978. A 5- to 6-year cycle in rabies incidence was clearly apparent, though no seasonality was noted. Male dogs had significantly increased odds of testing positive for RABV (odds ratio [OR]=1.14), as did 1- to 2-year-old dogs (OR=1.73); younger and older dogs were at lower risk. Samples submitted from the poorer suburbs of the city were more likely to test positive for RABV (OR=1.71). We estimated the distribution of endemic canine rabies in an urban environment to facilitate control measures in a resource-poor environment

    Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection

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    Significance The emergence of multidrug-resistant bacteria, including uropathogenic Escherichia coli (UPEC), makes the development of targeted antivirulence therapeutics a critical focus of research. During urinary tract infections (UTIs), UPEC uses chaperoneā€“usher pathway pili tipped with an array of adhesins that recognize distinct receptors with sterochemical specificity to facilitate persistence in various tissues and habitats. We used an interdisciplinary approach driven by structural biology and synthetic glycoside chemistry to design and optimize glycomimetic inhibitors of the UPEC adhesin FmlH. These inhibitors competitively blocked FmlH in vitro, in in vivo mouse UTI models, and in ex vivo healthy human kidney tissue. This work demonstrates the utility of structure-driven drug design in the effort to develop antivirulence therapeutic compounds. </jats:p

    During a winter of storms in a small UK catchment, hydrology and water quality responses follow a clear rural-urban gradient

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    This paper presents the hydrological and water quality response from a series of extreme storm events that passed across the UK during the winter of 2013/2014, in an experimental catchment with a strong rural-urban gradient across four nested sub-catchment areas. The Ray catchment in the upper Thames basin, UK, was extensively monitored using in-situ, high-resolution (15 minute) flow and water quality instrumentation. Dissolved oxygen, ammonium, turbidity and specific conductivity are used to characterise the water quality dynamics. The impact of the Swindon sewage treatment works (SSTW) on water chemistry at the catchment outlet is considerable. Hydrological and water-quality response varies considerably during the events, with the rural catchments exhibiting a much slower hydrological response compared to urban areas. A simple hydrological model (TETIS) was developed to provide insight into water sources in nested subcatchments, highlighting the disparity of the hydrological dynamics across contrasting land-uses during events. The variation in stormwater runoff sources impacts water quality signals with urban sites contributing to dilution dynamics in ammonium, whereas the more rural site experiences a peak in ammonium during the same event. Dissolved oxygen concentrations vary on a rural-urban gradient and experience a notable sag at the Water Eaton outlet (4.4mg/l) during the events, that would have resulted in significant ecological harm had they occurred during the summer in warmer temperatures. The water-quality legacy of these storms in the wider context of the hydrological year is somewhat negligible, with markedly poorer water quality signals being observed during the summer months of 2014. Although ammonium concentrations during the events are elevated (above the ā€˜goodā€™ status threshold under the WFD), higher values are observed during spring and summer months. The high flows actually appear to flush contaminants out of the Ray and its subcatchments, though the urban sites demonstrate a resupply dynamic during interim dry periods. Data suggest winter storms following dry spells in urban catchments cause some short-lived and spatially extensive deteriorations in water quality. More chronic effects, although prolonged, are only seen downstream of SSTW. These are indicative of capacity of infrastructure being reached, and from the data do not appear to be severe enough to cause ecological harm

    Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1

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    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated Ī²-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI-tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr83 and Glu73, respectively. When Glu73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu73 residue

    The Costs, Benefits and Human Behaviours for Antimicrobial Use in Small Commercial Broiler Chicken Systems in Indonesia

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    There are growing concerns over the threat to human health from the unregulated use of antimicrobials in livestock. Broiler production is of great economic and social importance in Indonesia. This study used a structured questionnaire approach to explore the human behaviours and economic drivers associated with antimicrobial use in small commercial broiler systems in Indonesia (n = 509). The study showed that antimicrobial use was high with farmers easily able to access antimicrobials through local animal medicine, however, it was difficult for farmers to access veterinary advice on responsible antimicrobial use. The most significant finding was that the relative cost of antimicrobials was low, and farmers observed improvements in productivity rates from routine antimicrobial administration. However, farmers seldom kept detailed records on farm productivity or economic costs; this is a hurdle to undertaking a more detailed economic analysis of antimicrobial use. There is a need for further research on the cost-effectiveness of alternative methods of preventing disease and ensuring that feasible alternatives are easily available. Farm-level economics and securing the food supply chain need to be central to any future policy interventions to reduce antimicrobial use in broiler systems in Indonesia and this observation is relevant at a regional and global level.</jats:p

    Associations between motor competence and physical activity levels of children with intellectual disabilities and/or autism spectrum disorder: movement matters

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    Motor competence is important for lifelong physical activity (PA). The current study aimed to examine associations between PA and motor competence. In total, 43 children aged 7ā€“12 years with intellectual disabilities and/or autism spectrum disorder completed anthropometric measures, the Bruininks-Oseretsky Test of Motor Proficiency-2, and wore a wrist accelerometer to capture total PA, moderate-to-vigorous PA (MVPA), average acceleration, and intensity gradient. No significant associations were found between PA outcomes and motor competence. Motor competence performance was commonly ā€˜below averageā€™ or ā€˜averageā€™. The weakest subtests were upper limb coordination and strength. The strongest subtest was running speed and agility. Total weekly MVPA was 336.1 Ā± 150.3 min, higher than UK recommendations of 120-180 per week for disabled children and young people. Larger scale studies are needed to better understand the relationship between PA and motor competence. Future research should also consider the influence of environmental factors on PA in this group

    Physical activity, mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis

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    ObjectivesTo assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governmentsā€™ Coronavirus disease (COVID-19) containment responses.DesignObservational, cross-sectional.MethodsAn online survey was disseminated to adults (n = 8,425; 44.5 Ā± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9.ResultsParticipants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001).ConclusionThe initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation

    Characterizing Antimicrobial Use in the Livestock Sector in Three South East Asian Countries (Indonesia, Thailand, and Vietnam)

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    A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was high in all sectors studied, and that routine preventative use was of particular importance to broiler production systems. Misleading feed labeling was identified as a hurdle to the collection of accurate antimicrobial use data, with farmers being unaware of the antimicrobials contained in some commercial feed. Economic analysis found that the cost of antimicrobials was low relative to other farm inputs, and that farm profitability was precariously balanced. High disease and poor prices were identified as potential drivers toward economic loss. The research indicates that antimicrobial use in small-scale poultry production systems improves feed conversion ratios and overall productivity. However, data were limited to quantify adequately these potential gains and their impacts on the food supply. During the study, all countries embraced and implemented policies on better management of antimicrobial use in livestock and surveillance of antimicrobial resistance. Future policies need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region
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