130 research outputs found
A semantic web service-based architecture for the interoperability of e-government services
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
An adaptive moving mesh method for forced curve shortening flow
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 Ξ²
Background: Altered expression of DNA polymerase Ξ² (Pol Ξ²) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol Ξ² 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 Ξ². 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 Ξ² over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol Ξ² expression. We observed elevated expression of Pol Ξ² in stomach adenomas and thyroid follicular carcinomas, but reduced Pol Ξ² 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
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, Δ₯Β²/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 Δ₯Β²/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 Δ₯Β²/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
Neotenic phenomenon in gene expression in the skin of Foxn1- deficient (nude) mice - a projection for regenerative skin wound healing
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