934 resultados para Alonso de Mella
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138 p.
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Background: Type 2 diabetes mellitus is associated with a diverse range of pathologies. The aim of the study was to determine the incidence of diabetes-related complications, the prevalence of coexistent chronic conditions and to report multimorbidity in people with type 2 diabetes living in the Basque Country. Methods: Administrative databases, in four cross sections (annually from 2007 to 2011) were consulted to analyse 149,015 individual records from patients aged >= 35 years with type 2 diabetes mellitus. The data observed were: age, sex, diabetes-related complications (annual rates of acute myocardial infarction, major amputations and avoidable hospitalisations), diabetes-related pathologies (prevalence of ischaemic heart disease, renal failure, stroke, heart failure, peripheral neuropathy, foot ulcers and diabetic retinopathy) and other unrelated pathologies (44 diseases). Results: The annual incidence for each condition progressively decreased during the four-year period: acute myocardial infarction (0.47 to 0.40%), major amputations (0.10 to 0.08%), and avoidable hospitalisations (5.85 to 5.5%). The prevalence for diabetes-related chronic pathologies was: ischaemic heart disease (11.5%), renal failure (8.4%), stroke (7.0%), heart failure (4.3%), peripheral neuropathy (1.3%), foot ulcers (2.0%) and diabetic retinopathy (7.2%). The prevalence of multimorbidity was 90.4%. The highest prevalence for other chronic conditions was 73.7% for hypertension, 13.8% for dyspepsia and 12.7% for anxiety. Conclusions: In the type 2 diabetes mellitus population living in the Basque Country, incidence rates of diabetes complications are not as high as in other places. However, they present a high prevalence of diabetes related and unrelated diseases. Multimorbidity is very common in this group, and is a factor to be taken into account to ensure correct clinical management.
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Este trabalho apresenta uma arquitetura geral para evolução de circuitos eletrônicos analógicos baseada em algoritmos genéticos. A organização lógica privilegia a interoperabilidade de seus principais componentes, incluindo a possibilidade de substituição ou melhorias internas de suas funcionalidades. A plataforma implementada utiliza evolução extrínseca, isto é, baseada em simulação de circuitos, e visa facilidade e flexibilidade para experimentação. Ela viabiliza a interconexão de diversos componentes aos nós de um circuito eletrônico que será sintetizado ou adaptado. A técnica de Algoritmos Genéticos é usada para buscar a melhor forma de interconectar os componentes para implementar a função desejada. Esta versão da plataforma utiliza o ambiente MATLAB com um toolbox de Algoritmos Genéticos e o PSpice como simulador de circuitos. Os estudos de caso realizados apresentaram resultados que demonstram a potencialidade da plataforma no desenvolvimento de circuitos eletrônicos adaptativos.
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142 p.
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270 p.
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250 p. + anexos
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180 p.
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In a multi-target complex network, the links (L-ij) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K-i, K-m, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.
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162 p.
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This paper deals with the convergence of a remote iterative learning control system subject to data dropouts. The system is composed by a set of discrete-time multiple input-multiple output linear models, each one with its corresponding actuator device and its sensor. Each actuator applies the input signals vector to its corresponding model at the sampling instants and the sensor measures the output signals vector. The iterative learning law is processed in a controller located far away of the models so the control signals vector has to be transmitted from the controller to the actuators through transmission channels. Such a law uses the measurements of each model to generate the input vector to be applied to its subsequent model so the measurements of the models have to be transmitted from the sensors to the controller. All transmissions are subject to failures which are described as a binary sequence taking value 1 or 0. A compensation dropout technique is used to replace the lost data in the transmission processes. The convergence to zero of the errors between the output signals vector and a reference one is achieved as the number of models tends to infinity.
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Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.
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We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans.
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[ES]En la problemática medioambiental generada por la contaminación atmosférica hay tres aspectos que marcan las directrices de actuación institucional: la presión social, la legislación vigente y la tecnología disponible. En cuanto a este último aspecto, la biofiltración es una tecnología eficaz, asequible y sostenible basada en la actividad biodegradadora de microorganismos específicos adheridos a la superficie de un material soporte que constituye el lecho del biofiltro. La elección de un material soporte adecuado es de especial importancia para asegurar el correcto funcionamiento de los biofiltros. Esta decisión está basada en las propiedades intrínsecas del material que deben ser analizadas previamente a su uso. En este proyecto se ha seleccionado cuales son estas propiedades básicas a partir de una revisión bibliográfica, destacando la capacidad de retención de humedad, superficie específica, porosidad, y estabilidad física y química del material. En este trabajo, también se han fijado los parámetros de control que deben ser medidos de forma rutinaria en un biofiltro para asegurar la eficacia del tratamiento de descontaminación. En base a la información bibliográfica recopilada, se ha concluido que los parámetros básicos son pH, temperatura, contenido de humedad del lecho y pérdidas de carga. A nivel experimental, se han medido las pérdidas de carga generadas en biofiltros empacados con tres materiales soportes que son de especial interés para una investigación posterior a desarrollar por el grupo Biofiltración de la Universidad del País Vasco (UPV/EHU). Durante el período de arranque inicial de los tres biofiltros, las pérdidas de carga medidas fueron muy bajas en los tres casos, aunque algo superiores cuando la alimentación era en sentido ascendente frente al flujo descendente. Sin embargo, cuando se midieron las pérdidas de carga bajo condiciones de encharcamiento del lecho, que es una de las situaciones más problemáticas en un biofiltro, todos los soportes presentaron un aumento puntual de la pérdida de carga aunque la tendencia en los días posteriores fue claramente descendente, recuperando valores de operación habituales. La comparativa del comportamiento frente a las pérdidas de carga permitió seleccionar el soporte más idóneo de los tres analizados, aunque los otros dos podrían ser alternativas viables en caso de sustitución.
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Dentre os muitos capítulos da gramática normativa, a colocação dos pronomes oblíquos átonos é um dos que mais apresenta diferenças entre o português do Brasil e o de Portugal. Neste trabalho, procuramos demonstrar que as regras poderiam ser simplificadas ou até mesmo reduzidas, com base no estudo de um corpus organizado a partir de textos formais, presentes em um dos principais veículos da mídia impressa brasileira, onde predomina a variedade padrão culta do idioma
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El trabajo consiste en el desarrollo del juego de los topos en HTML5. El objetivo del juego es golpear los topos antes de que se escondan para ir consiguiendo la mayor cantidad de puntos sin que se agoten las vidas.