595 research outputs found

    Orlicz-Sobolev nematic elastomers

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    We extend the existence theorems in Barchiesi et al. (2017), for models of nematic elastomers and magnetoelasticity, to a larger class in the scale of Orlicz spaces. These models consider both an elastic term where a polyconvex energy density is composed with an unknown state variable defined in the deformed configuration, and a functional corresponding to the nematic energy (or the exchange and magnetostatic energies in magnetoelasticity) where the energy density is integrated over the deformed configuration. In order to obtain the desired compactness and lower semicontinuity, we show that the regularity requirement that maps create no new surface can still be imposed when the gradients are in an Orlicz class with an integrability just above the space dimension minus one

    A Remarkably Stable Phosphorylated Form of Ca 2+ -ATPase Prepared from Ca 2+ -loaded and Fluorescein Isothiocyanate-labeled Sarcoplasmic Reticulum Vesicles

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    After the nucleotide binding domain in sarcoplasmic reticulum Ca2+-ATPase has been derivatized with fluorescein isothiocyanate at Lys-515, ATPase phosphorylation in the presence of a calcium gradient, with Ca2+ on the lumenal side but without Ca2+ on the cytosolic side, results in the formation of a species that exhibits exceptionally low probe fluorescence (Pick, U. (1981) FEBS Lett. 123, 131-136). We show here that, as long as the free calcium concentration on the cytosolic side is kept in the nanomolar range, this low fluorescence species is remarkably stable, even when the calcium gradient is subsequently dissipated by ionophore. This species is a Ca2+-free phosphorylated species. The kinetics of Ca2+ binding to it indicates that its transport sites are exposed to the cytosolic side of the membrane and retain a high affinity for Ca2+. Thus, in the ATPase catalytic cycle, an intrinsically transient phosphorylated species with transport sites occupied but not yet occluded must also have been stabilized by fluorescein isothiocyanate (FITC), possibly mimicking ADP. The low fluorescence mainly results from a change in FITC absorption. The Ca2+-free low fluorescence FITC-ATPase species remains stable after addition of thapsigargin in the absence or presence of decavanadate, or after solubilization with dodecylmaltoside. The remarkable stability of this phosphoenzyme species and the changes in FITC spectroscopic properties are discussed in terms of a putative FITC-mediated link between the nucleotide binding domain and the phosphorylation domain in Ca2+-ATPase, and the possible formation of a transition state-like conformation with a compact cytosolic head. These findings might open a path toward structural characterization of a stable phosphorylated form of Ca2+-ATPase for the first time, and thus to further insights into the pump's mechanism

    A variational model for fracture and debonding of thin films under in-plane loadings

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    We study fracture and debonding of a thin stiff film bonded to a rigid substrate through a thin compliant layer, introducing a two-dimensional variational fracture model in brittle elasticity. Fractures are naturally distinguished between transverse cracks in the film (curves in 2D) and debonded surfaces (2D planar regions). In order to study the mechanical response of such systems under increasing loads, we formulate a dimension-reduced, rate-independent, irreversible evolution law accounting for both transverse fracture and debonding. We propose a numerical implementation based on a regularized formulation of the fracture problem via a gradient damage functional, and provide an illustration of its capabilities exploring complex crack patterns, showing a qualitative comparison with geometrically involved real life examples. Moreover, we justify the underlying dimension-reduced model in the setting of scalar-valued displacement fields by a rigorous asymptotic analysis using Γ-convergence, starting from the three-dimensional variational fracture (free-discontinuity) problem under precise scaling hypotheses on material and geometric parameters. © 2014 Elsevier Ltd

    Linear and machine learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease

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    Q1Q1Background: Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues. Methodology/principal findings: We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty. Conclusions/significance: The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance.https://orcid.org/0000-0002-8165-3198Revista Internacional - IndexadaA1N

    Estudio de peso y rendimiento en canal de las razas Sanmartinera, Cebú y sus cruces en los Llanos Orientales.

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    Evalúa el ganado Sanmartinero, Cebú y sus cruces con Charolais, en ganancia de peso, producción de carne y rendimiento en canal. Se utilizaron 18 novillos divididos en 6 grupos de 3 animales cada uno, así: Sanmartinero (SM) y Cebú (C) como razas puras, y Sm x C, C x Sm filial 2 (C x Sm F2), Sm x C F2 y Ch x C x Sm como cruces. Al destete los animales cruzados ganaron 160 gr mas por día que los puros, en el postdestete los puros ganaron mas peso por día que los cruzados. Los pesos promedios al finalizar la ceba en pasto braquiaria fueron: 436, 400, 483, 457, 431 y 468 kg y los pesos al presacrificio después de 24 horas de ayuno fueron: 399, 369, 448, 418, 395 y 429 kg para el Sm, C, Sm x C, C x Sm F2, Sm x C F2 y Ch x C x Sm, respectivamente. En el mismo orden de razas se obtuvieron los siguientes resultados: pesos promedios de las canales: 221, 216, 253, 243, 223 y 245 kg, rendimientos en canal: 55, 58, 56, 56, 56 y 57 por ciento, rendimientos en canal en base al peso vacío, sustrayendo el contenido intestinal: 61, 62, 60, 60, 62 y 62 por ciento. Se encontraron diferencias significativas para el peso de las canales entre puros y cruzados. El porcentaje promedio de la merma de los grupos postrefrigeración en 24 horas a 6 grados centígrados fue de 1.76 por ciento. En la evaluación de expendio, se presentaron diferencias significativas para el peso de los cortes de primera, segunda y tercera entre los puros y cruzadosGanado de doble propósito-Ganaderia doble proposit

    Impact of sensor-augmented pump therapy with predictive low-glucose management on hypoglycemia and glycemic control in patients with type 1 diabetes mellitus : 1-year follow-up

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    Q2Artículo original2625-2631AIMS: To describe real-life experience with sensor-augmented pump therapy with predictive low-glucose management (SAPT-PLGM), in terms of hypoglycemia and glycemic control after one year of follow-up in T1D patients with hypoglycemia as the main indication of therapy. METHODS: Retrospective cohort study under real life conditions. Baseline and one-year follow-up variables of glycemic control, hypoglycemia and glycemic variability were compared. RESULTS: Fifty patients were included, 31 on prior treatment with SAPT with low-glucose suspend (LGS) feature and 19 on multiple dose insulin injections (MDI). Mean HbA1c decreased in the MDI group (8.24%-7.08%; p = 0.0001). HbA1c change was not significant in the SAPT-LGS group. Area under the curve (AUC) below 70 mg/dl improved in both SAPT-LGS and MDI groups while AUC, %time and events below 54 mg/dl decreased in SAPT-LGS group. Glycemic variability improved in the MDI group. Less patients presented severe hypoglycemia with SAPT-PLGM in both groups, however the change was non-significant. CONCLUSIONS: Under real life conditions, SAPT-PLGM reduced metrics of hypoglycemia in patients previously treaded with MDI and SAPT-LGS without deteriorating glycemic control in SAPT-LGS patients, while improving it in patients treated with MDI

    Alelos de tiopurina metiltransferasa en población colombiana

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    La tiopurina metiltransferasa (TPMT) cataliza lainactivación de los fármacos tiopurinas (mercaptopurina,tioguanina y azatioprina) usados en el tratamiento de laleucemia linfoblástica aguda, enfermedades autoinmunes yen pacientes con órganos transplantados; no se conocensustratos endógenos de esta enzima. El polimorfismo delgen TPMT es el principal determinante de las diferenciasindividuales en cuanto a toxicidad y eficacia terapéutica deestos medicamentos. Las bases moleculares de dichopolimorfismo han sido establecidas para caucásicos, africanos,afro-americanos y asiáticos, pero no han sido estudiadasen amerindios ni mestizos latinoamericanos. En esteestudio se identificaron y determinaron en 140 voluntarioscolombianos de origen mestizo (edad promedio 27 años,51.4% hombres) las frecuencias de las cuatro variantesalélicas más comunes del gen: TPMT*2 (G238C), TPMT*3A(G460A and A719G), TPMT*3B (G460A) and TPMT*3C(A719G). Se hallaron 10 individuos heterocigotos para el alelo*3A y uno para el alelo *2; no se encontraron homocigotosmutados, ni los alelos *3B y *3C. De acuerdo con estos resultados,el 92.1% y el 7.9% de la población estudiada correspondena los fenotipos metiladores altos e intermedios,respectivamente. Esta distribución se asemeja más a la reportadaentre caucásicos, donde prevalece el alelo *3A y seencuentra el *2, que entre africanos y asiáticos, donde prevaleceel alelo *3C

    Alelos de tiopurina metiltransferasa en población colombiana

    Get PDF
    La tiopurina metiltransferasa (TPMT) cataliza lainactivación de los fármacos tiopurinas (mercaptopurina,tioguanina y azatioprina) usados en el tratamiento de laleucemia linfoblástica aguda, enfermedades autoinmunes yen pacientes con órganos transplantados; no se conocensustratos endógenos de esta enzima. El polimorfismo delgen TPMT es el principal determinante de las diferenciasindividuales en cuanto a toxicidad y eficacia terapéutica deestos medicamentos. Las bases moleculares de dichopolimorfismo han sido establecidas para caucásicos, africanos,afro-americanos y asiáticos, pero no han sido estudiadasen amerindios ni mestizos latinoamericanos. En esteestudio se identificaron y determinaron en 140 voluntarioscolombianos de origen mestizo (edad promedio 27 años,51.4% hombres) las frecuencias de las cuatro variantesalélicas más comunes del gen: TPMT*2 (G238C), TPMT*3A(G460A and A719G), TPMT*3B (G460A) and TPMT*3C(A719G). Se hallaron 10 individuos heterocigotos para el alelo*3A y uno para el alelo *2; no se encontraron homocigotosmutados, ni los alelos *3B y *3C. De acuerdo con estos resultados,el 92.1% y el 7.9% de la población estudiada correspondena los fenotipos metiladores altos e intermedios,respectivamente. Esta distribución se asemeja más a la reportadaentre caucásicos, donde prevalece el alelo *3A y seencuentra el *2, que entre africanos y asiáticos, donde prevaleceel alelo *3C
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