131 research outputs found

    A semantic web service-based architecture for the interoperability of e-government services

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    We propose a semantically-enhanced architecture to address the issues of interoperability and service integration in e-government web information systems. An architecture for a life event portal based on Semantic Web Services (SWS) is described. The architecture includes loosely-coupled modules organized in three distinct layers: User Interaction, Middleware and Web Services. The Middleware provides the semantic infrastructure for ontologies and SWS. In particular a conceptual model for integrating domain knowledge (Life Event Ontology), application knowledge (E-government Ontology) and service description (Service Ontology) is defined. The model has been applied to a use case scenario in e-government and the results of a system prototype have been reported to demonstrate some relevant features of the proposed approach

    Household Energy Efficiency – why the older owner is stalled.

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    Data shows continued failure to meet new-build targets which combined with low current retrofit works means UK housing stock consistently falls behind energy efficiency targets. The properties of concern are owned outright and occupied by pensioners. This briefing provides an overview, including the drivers, impacts and current research data finishing with clear policy advice to address the systemic causes. All the necessary infrastructure required to apply policy, regulatory and education levers already exist

    An adaptive moving mesh method for forced curve shortening flow

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    We propose a novel adaptive moving mesh method for the numerical solution of a forced curve shortening geometric evolution equation. Control of the mesh quality is obtained using a tangential mesh velocity derived from a mesh equidistribution principle, where a positive adaptivity measure or monitor function is approximately equidistributed along the evolving curve. Central finite differences are used to discretise in space the governing evolution equation for the position vector and a second-order implicit scheme is used for the temporal integration. Simulations are presented indicating the generation of meshes which resolve areas of high curvature and are of second-order accuracy. Furthermore, the new method delivers improved solution accuracy compared to the use of uniform arc-length meshes

    Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β

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    Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation

    Inheritance of DNA methylation level in healthy human tissues

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    DNA methylation (DNAm) is the covalent modification of DNA by addition of a methyl group primarily at the cytosine directly upstream of a guanine. DNAm level plays a central role in transcriptional regulation and is linked to disease. Therefore, understanding genetic and environmental influences on DNAm level in healthy tissue is an important step in the elucidation of trait and disease etiology. However, at present only a minority of easy to access human tissues and ethnicities have been investigated. Therefore, we studied DNAm level measured in five human tissues: cerebellum, frontal cortex, pons, temporal cortex and colon in either North American or South American samples. We applied a novel statistical approach to estimate the heritability attributable to genomic regions (regional heritability, ĥ²/r,g ) for DNAm level at thousands of individual DNAm sites genome-wide. In all five tissues, DNAm level was significantly associated with the local genomic region for more DNAm sites than expected by chance. Moreover, DNAm level could be predicted from the local sequence variants with an accuracy that scaled with the estimated ĥ²/r,g . Our results inform on molecular mechanisms regulating DNAm level and trait etiology in several ways. Firstly, DNAm level at DNAm sites located in genomic risk regions and measured in a tissue relevant to the disease can be influenced by the local genetic variants. Specifically, we found that genetic variation within a region associated with Fluid Intelligence was also associated with local DNAm level at the proline-rich coiled-coil 1 (PRRC1) gene in healthy temporal cortex tissue. Additionally, we replicated the finding of a Colorectal Cancer risk variant (rs4925386) associated with two DNAm sites in healthy colon tissue. More generally, we showed that DNAm sites located within a susceptibility region and measured in a relevant tissue exhibit a similar overall pattern of estimated ĥ²/r,g to DNAm sites outwith a susceptibility region. Secondly, the propensity for DNAm level to be associated with the local sequence variation differs with respect to CpG dinucleotide density and genic location. Most notably, DNAm sites located in CpG dense regions of the genome are less likely to be heritable than DNAm sites located in CpG sparse regions of the genome. Additionally, within both CpG dense and CpG sparse regions of the genome intergenic DNAm sites are more likely to be heritable than intragenic DNAm sites. Overall, our study suggests that variation in DNAm level at some DNAm sites is at least partially controlled by nuclear genetic variation. Moreover, DNAm level in healthy tissue has the potential to act as an intermediary in trait variation and etiology
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