3,186 research outputs found

    Space-mapping techniques applied to the optimization of a safety isolating transformer

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    Space-mapping optimization techniques allow to allign low-fidelity and high-fidelity models in order to reduce the computational time and increase the accuracy of the solution. The main idea is to build an approximate model from the difference of response between both models. Therefore the optimization process is computed on the surrogate model. In this paper, some recent approaches of space-mapping techniques such as agressive-space-mapping, output-mapping and manifold-mapping algorithms are applied to optimize a safety insulating transformer. The electric, magnetic and thermal phenomena of the device are modeled by an analytical model and a 3D finite element model. It is considered as a benchmark for multi-level optimization to test different algorithms

    Brief International Cognitive Assessment for MS (BICAMS): International Standards for Validation

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    An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1–3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS

    A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress.

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    : Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many parasite effector proteins, including perforins, adhesins, and proteases, are extensively proteolytically processed both pre- and postexocytosis. Here we report the multistage antiplasmodial activity of the aspartic protease inhibitor hydroxyl-ethyl-amine-based scaffold compound 49c. This scaffold inhibits the preexocytosis processing of several secreted rhoptry and microneme proteins by targeting the corresponding maturases plasmepsins IX (PMIX) and X (PMX), respectively. Conditional excision of PMIX revealed its crucial role in invasion, and recombinantly active PMIX and PMX cleave egress and invasion factors in a 49c-sensitive manner.<br/

    A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages

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    Critical events in the life cycle of malaria-causing parasites depend on cyclic guanosine monophosphate homeostasis by guanylyl cyclases (GCs) and phosphodiesterases, including merozoite egress or invasion of erythrocytes and gametocyte activation. These processes rely on a single GCalpha, but in the absence of known signaling receptors, how this pathway integrates distinct triggers is unknown. We show that temperature-dependent epistatic interactions between phosphodiesterases counterbalance GCalpha basal activity preventing gametocyte activation before mosquito blood feed. GCalpha interacts with two multipass membrane cofactors in schizonts and gametocytes: UGO (unique GC organizer) and SLF (signaling linking factor). While SLF regulates GCalpha basal activity, UGO is essential for GCalpha up-regulation in response to natural signals inducing merozoite egress and gametocyte activation. This work identifies a GC membrane receptor platform that senses signals triggering processes specific to an intracellular parasitic lifestyle, including host cell egress and invasion to ensure intraerythrocytic amplification and transmission to mosquitoes
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