16 research outputs found

    Least action principles and their application to constrained and task-level problems in robotics and biomechanics

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    International audienceLeast action principles provide an insightful starting point from which problems involving constraints and task-level objectives can be addressed. In this paper, the principle of least action is first treated with regard to holonomic constraints in multibody systems. A variant of this, the principle of least curvature or straightest path, is then investigated in the context of geodesic paths on constrained motion manifolds. Subsequently, task space descriptions are addressed and the operational space approach is interpreted in terms of least action. Task-level control is then applied to the problem of cost minimization. Finally, task-level optimization is formulated with respect to extremizing an objective criterion, where the criterion is interpreted as the action of the system. Examples are presented which illustrate these approaches

    Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

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    A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

    Keywords Least action · Constraints · Task-level control · Musculoskeletal system ·

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    Least action principles and their application to constrained and task-level problems in robotics and biomechanic
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