131 research outputs found

    Renewal reward perspective on linear switching diffusion systems

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    In many biological systems, the movement of individual agents is commonly characterized as having multiple qualitatively distinct behaviors that arise from various biophysical states. This is true for vesicles in intracellular transport, micro-organisms like bacteria, or animals moving within and responding to their environment. For example, in cells the movement of vesicles, organelles and other cargo are affected by their binding to and unbinding from cytoskeletal filaments such as microtubules through molecular motor proteins. A typical goal of theoretical or numerical analysis of models of such systems is to investigate the effective transport properties and their dependence on model parameters. While the effective velocity of particles undergoing switching diffusion is often easily characterized in terms of the long-time fraction of time that particles spend in each state, the calculation of the effective diffusivity is more complicated because it cannot be expressed simply in terms of a statistical average of the particle transport state at one moment of time. However, it is common that these systems are regenerative, in the sense that they can be decomposed into independent cycles marked by returns to a base state. Using decompositions of this kind, we calculate effective transport properties by computing the moments of the dynamics within each cycle and then applying renewal-reward theory. This method provides a useful alternative large-time analysis to direct homogenization for linear advection-reaction-diffusion partial differential equation models. Moreover, it applies to a general class of semi-Markov processes and certain stochastic differential equations that arise in models of intracellular transport. Applications of the proposed framework are illustrated for case studies such as mRNA transport in developing oocytes and processive cargo movement by teams of motor proteins.Comment: 35 pages, 6 figure

    Oxygen reduction reaction at La<sub>x</sub>Ca<sub>1-x</sub>MnO<sub>3</sub> nanostructures: interplay between A-site segregation and B-site valency

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    The mean activity of surface Mn sites at LaxCa1-xMnO3 nanostructures towards the oxygen reduction reaction (ORR) in alkaline solution is assessed as a function of the oxide composition. Highly active oxide nano-particles were synthesised by an ionic liquid-based route, yielding phase-pure nanoparticles, across the entire range of compositions, with sizes between 20 and 35 nm. The bulk vs. surface composition and structure are investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge spectroscopy (XANES). These techniques allow quantification of not only changes in the mean oxidation state of Mn as a function of x, but also the extent of A-site surface segregation. Both trends manifest themselves in the electrochemical responses associated with surface Mn sites in 0.1 M KOH solution. The characteristic redox signatures of Mn sites are used to estimate their effective surface number density. This parameter allows comparing, for the first time, the mean electrocatalytic activity of surface Mn sites as a function of the LaxCa1-xMnO3 composition. The ensemble of experimental data provides a consistent picture in which increasing electron density at the Mn sites leads to an increase in the ORR activity. We also demonstrate that normalisation of electrochemical activity by mass or specific surface area may result in inaccurate structure–activity correlations

    KELVIN: A Software Package for Rigorous Measurement of Statistical Evidence in Human Genetics

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    This paper describes the software package KELVIN, which supports the PPL (posterior probability of linkage) framework for the measurement of statistical evidence in human (or more generally, diploid) genetic studies. In terms of scope, KELVIN supports two-point (trait-marker or marker-marker) and multipoint linkage analysis, based on either sex-averaged or sex-specific genetic maps, with an option to allow for imprinting; trait-marker linkage disequilibrium (LD), or association analysis, in case-control data, trio data, and/or multiplex family data, with options for joint linkage and trait-marker LD or conditional LD given linkage; dichotomous trait, quantitative trait and quantitative trait threshold models; and certain types of gene-gene interactions and covariate effects. Features and data (pedigree) structures can be freely mixed and matched within analyses. The statistical framework is specifically tailored to accumulate evidence in a mathematically rigorous way across multiple data sets or data subsets while allowing for multiple sources of heterogeneity, and KELVIN itself utilizes sophisticated software engineering to provide a powerful and robust platform for studying the genetics of complex disorders

    Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

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    Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

    Long-range angular correlations on the near and away side in p&#8211;Pb collisions at

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