131 research outputs found

    Molecular Recognition between Cadherins Studied by a Coarse-Grained Model Interacting with a Coevolutionary Potential

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    Studying the conformations involved in the dimerization of cadherins is highly relevant to understand the development of tissues and its failure, which is associated with tumors and metastases. Experimental techniques, like X-ray crystallography, can usually report only the most stable conformations, missing minority states that could nonetheless be important for the recognition mechanism. Computer simulations could be a valid complement to the experimental approach. However, standard all-atom protein models in explicit solvent are computationally too demanding to search thoroughly the conformational space of multiple chains composed of several hundreds of amino acids. To reach this goal, we resorted to a coarse-grained model in implicit solvent. The standard problem with this kind of model is to find a realistic potential to describe its interactions. We used coevolutionary information from cadherin alignments, corrected by a statistical potential, to build an interaction potential, which is agnostic about the experimental conformations of the protein. Using this model, we explored the conformational space of multichain systems and validated the results comparing with experimental data. We identified dimeric conformations that are sequence specific and that can be useful to rationalize the mechanism of recognition between cadherins

    Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

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    Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy

    Open source in South African schools : two case studies

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    One of the major problems facing schools in South Africa is the difficulty in obtaining modern, up-to-date computer facilities. This paper looks at the use of open source solutions in two government schools in South Africa to demonstrate that it is possible for schools to utilise almost any existing computer to provide effective network solutions

    Using JAIN SLEE as an Interaction and Policy Manager for Enabler-based Services in Next Generation Networks

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    The IP Multimedia Subsystem is a telecommunications framework with a standard architecture for the provision of services. While the services themselves have not been standardised, standards do exist for basic technologies that can be re-used and aggregated in order to construct more complex services. These elements are called service capabilities by the 3GPP and service enablers by the OMA, both of which are reputable standards bodies in this area. In order to provide re-usability, there is a need to manage access to the service capabilities. Also, in order to build complex services, there is a further need to be able to manage and coordinate the interactions that occur between service capabilities. The 3GPP and the OMA have separately defined network entities that are responsible for handling aspects of these requirements, and are known as a service capability interaction manager (SCIM) and a policy enforcer respectively. However, the internal structure of the SCIM and the policy enforcer have not been standardised by the relevant bodies. In addition, as the SCIM and the policy enforcer have been defined through complementary yet separate processes, there is an opportunity to unify efforts from both bodies. This paper builds on work and standards defined by the bodies, and proposes the design of an interaction manager with features borrowed from both the SCIM and the policy enforcer. To help validate the design, we have identified a platform known as JAIN SLEE which we believe conforms to the model proposed, and we discuss how JAIN SLEE can be used to implement our ideas

    Transitions towards a knowledge society: Aspectual pre-evaluation of a culture-sensitive implementation framework

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    Information and Communication Technology (ICT) is aiding the transi-tion of society into information society and ultimately knowledge society. Embedded within ICT are the cultural and philosophical undercurrents of the society in which the ICT solutions are developed, currently pre-dominantly the Western culture. The proliferation of ICT is therefore in-advertedly leading to more Westernization of the world. It is important, therefore, that ICT solutions are culture sensitive and flexible enough to be situated within different cultures. To that end, we utilize Herman Dooyeweerd’s Theory of Modal Aspects to analyze a framework we has developed for implementation of locally situated knowledge based systems, to determine its efficacy in addressing the different modal as-pects, which make up the total experience and cultural expressiveness of societies

    eServices provisioning in a community development context through a JADE MAS platform

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    A growing proliferation of ICT4D interventions has necessitated the ex-ploration of innovative solutions for the provisioning of eServices in ru-ral, marginalized communities. The challenges currently faced in these interventions include: situating the developed applications within the cultural and ethnographic context of the target communities, integrating greater levels of granularity and flexibility within the applications for in-creased context sensitivity, handling the intermittence and instability of supporting infrastructural services. These are the challenges that we address in the context of ICT4D intervention undertaken in a rural community in the Eastern Cape province of South Africa. We explore the design and implementation of a Multi-Agent System (MAS) for this community as a platform for provisioning of context-sensitive eServ-ices, and highlight some observations with regards to the applicability and adequacy of the solution
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