263 research outputs found

    Fluctuation dynamo and turbulent induction at low magnetic Prandtl numbers

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    This paper is a detailed report on a programme of simulations used to settle a long-standing issue in the dynamo theory and demonstrate that the fluctuation dynamo exists in the limit of large magnetic Reynolds number Rm>>1 and small magnetic Prandtl number Pm<<1. The dependence of the critical Rm_c vs. the hydrodynamic Reynolds number Re is obtained for 1<Re<6700. In the limit Pm<<1, Rm_c is ~3 times larger than for Pm>1. The stability curve Rm_c(Re) (and, it is argued, the nature of the dynamo) is substantially different from the case of the simulations and liquid-metal experiments with a mean flow. It is not as yet possible to determine numerically whether the growth rate is ~Rm^{1/2} in the limit Re>>Rm>>1, as should be the case if the dynamo is driven by the inertial-range motions. The magnetic-energy spectrum in the low-Pm regime is qualitatively different from the Pm>1 case and appears to develop a negative spectral slope, although current resolutions are insufficient to determine its asymptotic form. At 1<Rm<Rm_c, the magnetic fluctuations induced via the tangling by turbulence of a weak mean field are investigated and the possibility of a k^{-1} spectrum above the resistive scale is examined. At low Rm<1, the induced fluctuations are well described by the quasistatic approximation; the k^{-11/3} spectrum is confirmed for the first time in direct numerical simulations.Comment: IoP latex, 27 pages, 25 figures, 3 tables. Accepted by New J. Physic

    A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor

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    Background: Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib. Methods: This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion. Results: Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8–4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%). Conclusions: The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing

    Informed Decisions for Actions in Maternal and Newborn Health 2010–17 Report What works, why and how in maternal and newborn health

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    IDEAS is a measurement, learning and evaluation project based at the London School of Hygiene & Tropical Medicine (LSHTM). The project aims to find out “what works, why, and how” for maternal and newborn health in three low-resource settings in Nigeria, India, and Ethiopia. The IDEAS team includes 20 research and professional support staff, living in Abuja, Addis Ababa, London, and New Delhi, who have been working since 2010 with the Bill & Melinda Gates Foundation (the foundation) and with the foundation’s implementation partners

    Almost exponential maps and integrability results for a class of horizontally regular vector fields

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    We show a higher order integrability theorem for distributions generated by a family of vector fields under a horizontal regularity assumption on their coefficients. We use as chart a class of almost exponential maps which we discuss in detailsComment: arXiv admin note: material from arXiv:1106.2410v1, now three separate articles arXiv:1106.2410v2, arXiv:1201.5228, arXiv:1201.520

    Structure and Dynamics of Amyloid-β Segmental Polymorphisms

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    Conceived and designed the experiments: WB UH. Performed the experiments: WB. Analyzed the data: WB UH. Contributed reagents/materials/analysis tools: WB UH. Wrote the paper: WB UH.It is believed that amyloid-beta (Aβ) aggregates play a role in the pathogenesis of Alzheimer’s disease. Aβ molecules form β-sheet structures with multiple interaction sites. This polymorphism gives rise to differences in morphology, physico-chemical property and level of cellular toxicity. We have investigated the conformational stability of various segmental polymorphisms using molecular dynamics simulations and find that the segmental polymorphic models of Aβ retain a U-shaped architecture. Our results demonstrate the importance of inter-sheet side chain-side chain contacts, hydrophobic contacts among the strands (β1 and β2) and of salt bridges in stabilizing the aggregates. Residues in β-sheet regions have smaller fluctuation while those at the edge and loop region are more mobile. The inter-peptide salt bridges between Asp23 and Lys28 are strong compared to intra-chain salt bridge and there is an exchange of the inter-chain salt-bridge with intra-chain salt bridge. As our results suggest that Aβ exists under physiological conditions as an ensemble of distinct segmental polymorphs, it may be necessary to account in the development of therapeutics for Alzheimer’s disease the differences in structural stability and aggregation behavior of the various Aβ polymorphic forms.Yeshttp://www.plosone.org/static/editorial#pee

    Computational Modeling of Silicate Glasses: A Quantitative Structure-Property Relationship Perspective

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    This article reviews the present state of Quantitative Structure-Property Relationships (QSPR) in glass design and gives an outlook into future developments. First an overview is given of the statistical methodology, with particular emphasis to the integration of QSPR with molecular dynamics simulations to derive informative structural descriptors. Then, the potentiality of this approach as a tool for interpretative and predictive purposes is highlighted by a number of recent inspiring applications
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