2,562 research outputs found

    PMH77 ANTIPSYCHOTIC METABOLIC PROPENSITY AND POLYTHERAPY: INFLUENCE ON HOSPITALIZATION

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    Partially liquid-filled hollow-core photonic crystal fiber polarizer

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    2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    3D geometric modelling of discontinuous fibre composites using a force-directed algorithm

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    A geometrical modelling scheme is presented to produce representative architectures for discontinuous fibre composites, enabling downstream modelling of mechanical properties. The model generates realistic random fibre architectures containing high filament count bundles (>3k) and high (~50%) fibre volume fractions. Fibre bundles are modelled as thin shells using a multi-dimension modelling strategy, in which fibre bundles are distributed and compacted to simulate pressure being applied from a matched mould tool. FE simulations are performed to benchmark the in-plane mechanical properties obtained from the numerical model against experimental data, with a detailed study presented to evaluate the tensile properties at various fibre volume fractions and specimen thicknesses. Tensile modulus predictions are in close agreement (less than 5% error) with experimental data at volume fractions below 45%. Ultimate tensile strength predictions are within 4.2% of the experimental data at volume fractions between 40%-55%. This is a significant improvement over existing 2D modelling approaches, as the current model offers increased levels of fidelity, capturing dominant failure mechanisms and the influence of out-of-plane fibres

    Four small puzzles that Rosetta doesn't solve

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    A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

    The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

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    Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

    A self-organized model for cell-differentiation based on variations of molecular decay rates

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    Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

    Measurement of the Negative Muon Anomalous Magnetic Moment to 0.7 ppm

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    The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 parts per million (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement of the negative muon. The result a_mu= 11 659 214(8)(3) \times 10^{-10} (0.7 ppm), where the first uncertainty is statistical and the second is sytematic, is consistend with previous measurements of the anomaly for the positive and negative muon. The average for the muon anomaly a_{mu}(exp) = 11 659 208(6) \times 10^{-10} (0.5ppm).Comment: 4 pages, 4 figures, submitted to Physical Review Letters, revised to reflect referee comments. Text further revised to reflect additional referee comments and a corrected Fig. 3 replaces the older versio

    Criteria for clinical audit of women friendly care and providers' perception in Malawi

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    Background There are two dimensions of quality of maternity care, namely quality of health outcomes and quality as perceived by clients. The feasibility of using clinical audit to assess and improve the quality of maternity care as perceived by women was studied in Malawi. Objective We sought to (a) establish standards for women friendly care and (b) explore attitudinal barriers which could impede the proper implementation of clinical audit. Methods We used evidence from Malawi national guidelines and World Health Organisation manuals to establish local standards for women friendly care in three districts. We equally conducted a survey of health care providers to explore their attitudes towards criterion based audit. Results The standards addressed different aspects of care given to women in maternity units, namely (i) reception, (ii) attitudes towards women, (iii) respect for culture, (iv) respect for women, (v) waiting time, (vi) enabling environment, (vii) provision of information, (viii) individualised care, (ix) provision of skilled attendance at birth and emergency obstetric care, (x) confidentiality, and (xi) proper management of patient information. The health providers in Malawi generally held a favourable attitude towards clinical audit: 100.0% (54/54) agreed that criterion based audit will improve the quality of care and 92.6% believed that clinical audit is a good educational tool. However, there are concerns that criterion based audit would create a feeling of blame among providers (35.2%), and that manager would use clinical audit to identify and punish providers who fail to meet standards (27.8%). Conclusion Developing standards of maternity care that are acceptable to, and valued by, women requires consideration of both the research evidence and cultural values. Clinical audit is acceptable to health professionals in Malawi although there are concerns about its negative implications to the providers
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