20 research outputs found

    Asthma-susceptibility variants identified using probands in case-control and family-based analyses

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    <p>Abstract</p> <p>Background</p> <p>Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.</p> <p>Methods</p> <p>We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings.</p> <p>Results</p> <p>We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung.</p> <p>Conclusions</p> <p>Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.</p

    High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

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    The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

    Grant-aided flood management strategies in Scotland and England between 1994 and 2004 : drivers, policy and practice

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    This thesis investigates the nature of grant-aided flood management strategies for watercourses approved in England and Scotland between 1994 and 2004. A database of 595 grant-aided fluvial flood management strategies was established to classify the character of practice over this period. The presence or absence of 119 distinct measures of practice were placed in 10 Groups (e. g. Walls, Attenuation or Non- Structural), and used with cluster analysis to identify three types of practice: those relating to structural barriers, pumping stations and modifications to the channel. Structural measures dominated the database. Multivariate statistical analyses (principal components analysis, chi-squared tests and discriminant analysis) were used to quantify the main operational drivers upon practice. New associations were found between the presence or absence of Groups of practices and the nature of existing flood management activities, environmental designations, standard of protection, operating authority type and, most significantly, catchment characteristics. Catchment slope, size, urbanisation, base flow and wetness characteristics were found by discriminant analysis to be able to correctly predict the type of strategy in nearly 60% of cases, illustrating the degree of influence exerted by physical factors. Spatial and temporal patterns were examined. Regional patterns in flood management practice were influenced by catchment characteristics and the type of operating authority responsible. Strategies in Scotland were designed to a higher standard of protection and were proportionally more likely to involve Attenuation or Adaptation measures than their English counterparts. Invasive techniques such as those to increase conveyance, or those involving inchannel construction, decreased in frequency of implementation. Non-Structural measures and those deemed as Adaptation saw an increase in adoption over the 10- year period. Through investigation of a small sample of rejected alternatives, a rise in the appraisal of land use modifications was observed. These results illustrate a shift away from structural dominance, in line with calls for sustainable flood management.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Countrywide flood forecasting in Scotland: challenges for hydrometeorological model uncertainty and prediction

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    The Scottish Flood Forecasting Service, a new partnership between the Met Office and the Scottish Environment Protection Agency, aims to make best use of weather and river forecasting expertise in providing improved flood resilience and vigilance for emergency responders across Scotland. Flood guidance employs a blend of experience, professional assessment and input from meteorological and hydrological models. For countrywide forecasts, the CEH-developed Grid-to-Grid model is planned to be the key forecasting tool: it employs rainfall estimates from raingauges, radar and weather models to produce forecast river flows up to 5 days ahead on a 1-km grid across the Scottish mainland. Probabilistic flood forecasts, using ensemble rainfalls as input, are planned in a future phase. Use of rainfall as input to hydrological models is a challenge in Scotland, especially given the terrain and sparse radar and raingauge network coverage, and makes forecasting uncertain. However, the merged hydrological and meteorological capabilities of the new service bring tangible benefits for improved flood forecasting

    High-Confidence Glycosome Proteome for Procyclic Form <i>Trypanosoma brucei</i> by Epitope-Tag Organelle Enrichment and SILAC Proteomics

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    The glycosome of the pathogenic African trypanosome <i>Trypanosoma brucei</i> is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

    High-Confidence Glycosome Proteome for Procyclic Form <i>Trypanosoma brucei</i> by Epitope-Tag Organelle Enrichment and SILAC Proteomics

    No full text
    The glycosome of the pathogenic African trypanosome <i>Trypanosoma brucei</i> is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed
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