105 research outputs found

    Procedimiento para el ejercicio de la clínica de pequeños animales

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    Treball presentat a la Facultat de Veterinària de la Universitat Autònoma de Barcelona.Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

    Estudio de la estructura cuaternaria de p53 y el cpmplejo p53/ADN mediante microscopía electrónica

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    Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid. Facultad de Ciencias. Departamento de Biología Molecular. Fecha de lectura: 16/04/201

    Mechanical properties and fracture behaviour of ODS Steel Friction Stir Welds at variable temperatures

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    We have assessed the microstructure and the temperature-dependent mechanical behaviour of five bead-on-plate friction stir welds of Oxide Dispersion Strengthened (ODS) steel, produced using systematic changes to the tool rotation and traverse speed. Friction stir welding can potentially retain the fine dispersion of nanoparticles, and therefore also the high-temperature strength and radiation damage resistance of these materials. Tensile testing was carried out on the MA956 base material at a range of temperatures, from room temperature up to 750 °C. The mechanical properties of the welds were investigated via tensile testing at room temperature and at 500 °C, together with micro-hardness testing. The welds exhibited similar strength and ductility to the base material at both testing temperatures as welding caused a partial loss of particle strengthening, alongside an increase in grain boundary strengthening due to a greatly refined grain size in the stir zones. The micro-hardness data revealed a trend of increasing hardness with increasing tool traverse speed or decreasing rotation speed. This was attributed to the smaller grain size and lower nanoparticle number density in the welds created with these parameters. At 500 °C, the yield stress and ultimate tensile stress of the base material and the welds decreased, due to a progressive reduction in both the Orowan-type particle strengthening and the grain boundary strengthening.</p

    System-on-Chip for Real-Time Satellite Photovoltaic Curves Telemetry

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    This paper presents a System-on-Chip design for real-time satellites photovoltaic curves telemetry. In these applications, the limitation of memory and communication bandwidth makes quite difficult to store and to transmit the whole characteristic current-voltage (I–V) curve of any solar section in real-time. The proposed solution is based on the real-time calculation of the equivalent singlediode model of the solar section. The single-diode model fits accurately the behavior of any solar panel, so once the parameters are calculated, saved, and transmitted, at any working conditions, that specific curve could be later reproduced. The system is based on a LEON3 32-bit microprocessor core implemented in a Field Programmable Gate Array. The LEON microprocessors were originally designed by the European Space Agency, Paris, France, to be used in space projects where high reliability is required. In addition, in order to design the system as simple and reliable as possible, from all the methods available in the literature to extract the five parameters of the equivalent model, the Oblique Asymptote Method has been chosen for its simplicity and precision. Finally, some experimental results are presented to demonstrate the accuracy of the final system

    Modelos para estimación de curvas de potencia de referencia aplicadas al análisis del rendimiento de aerogeneradores

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    El análisis del rendimiento de las curvas de potencia de aerogeneradores requiere un filtrado y caracterización de las mismas. Este filtrado identifica aquellos valores de la curva de potencia en los que la producción es inferior a la esperada, permitiendo analizar el rendimiento y la definición de una curva media que la caracteriza. Los métodos estáticos de filtrado y caracterización actuales presentan, en general, limitaciones en cuanto a su adaptación al comportamiento real del aerogenerador analizado para las condiciones de trabajo existentes. Requieren de la intervención de un técnico cualificado que los supervise, lo que incluye un factor de subjetividad importante y además imposibilita la aplicación de dichos métodos de trabajo en una aplicación informática autónoma. El análisis de los métodos de trabajo actuales, de sus carencias y de los requisitos necesarios para su automatización, dan lugar a nuevos métodos dinámicos de filtrado. Estos nuevos métodos de filtrado deben ser eficientes y permitir un compromiso razonable entre los resultados obtenidos manualmente y los de los algoritmos que puedan automatizar el proceso de cálculo. Los métodos dinámicos de filtrado y caracterización de curvas de potencia permiten su adaptación al comportamiento real del aerogenerador para las condiciones de trabajo existentes. En ellos previamente se analiza un modelo que morfológicamente permite caracterizar a una curva de potencia de un aerogenerador (En este caso, Distribución Normal Acumulada de Gauss). A continuación se define la ecuación correspondiente a dicho modelo y se optimizan los parámetros que la definen con el fin de ajustar el modelo al comportamiento concreto de la máquina y periodo analizados. A continuación se definen los umbrales de filtrado de la curva de referencia y se estima el Rendimiento de la máquina, (función de mérito utilizada, muy sensible a la calidad del filtrado). Se comparan las estimaciones de la función de mérito para cada método comparándolo con un óptimo, el tratamiento manual de los datos por un técnico cualificado. Finalmente, se evalúan las desviaciones de cada método respecto al óptimo y analizan las ventajas e inconvenientes de cada uno. Con esto, se define un método de estimación del rendimiento de aerogeneradores que alcanza un equilibrio entre calidad, recursos necesarios y posibilidades de automatización del proces

    Structures of SMG1-UPFs Complexes: SMG1 Contributes to Regulate UPF2-Dependent Activation of UPF1 in NMD

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    SummarySMG1, a PI3K-related kinase, plays a critical role in nonsense-mediated mRNA decay (NMD) in mammals. SMG1-mediated phosphorylation of the UPF1 helicase is an essential step during NMD initiation. Both SMG1 and UPF1 are presumably activated by UPF2, but this regulation is incompletely understood. Here we reveal that SMG1C (a complex containing SMG1, SMG8, and SMG9) contributes to regulate NMD by recruiting UPF1 and UPF2 to distinct sites in the vicinity of the kinase domain. UPF2 binds SMG1 in an UPF1-independent manner in vivo, and the SMG1C-UPF2 structure shows UPF2 recognizes the FRB domain, a region that regulates the related mTOR kinase. The molecular architectures of several SMG1C-UPFs complexes, obtained by combining electron microscopy with in vivo and in vitro interaction analyses, competition experiments, and mutations, suggest that UPF2 can be transferred to UPF1 within SMG1C, inducing UPF2-dependent conformational changes required to activate UPF1 within an SMG1C-UPF1-UPF2 complex

    Modulation of the chaperone DnaK allosterism by the nucleotide exchange factor GrpE

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    10 p.-6 fig.Hsp70 chaperones comprise two domains, the nucleotide-binding domain (Hsp70NBD), responsible for structural and functional changes in the chaperone, and the substrate-binding domain (Hsp70SBD), involved in substrate interaction. Substrate binding and release in Hsp70 is controlled by the nucleotide state of DnaKNBD, with ATP inducing the open, substrate-receptive DnaKSBD conformation, whereas ADP forces its closure. DnaK cycles between the two conformations through interaction with two cofactors, the Hsp40 co-chaperones (DnaJ in Escherichia coli) induce the ADP state, and the nucleotide exchange factors (GrpE in E. coli) induce the ATP state. X-ray crystallography showed that the GrpE dimer is a nucleotide exchange factor that works by interaction of one of its monomers with DnaKNBD. DnaKSBD location in this complex is debated; there is evidence that it interacts with the GrpE N-terminal disordered region, far from DnaKNBD. Although we confirmed this interaction using biochemical and biophysical techniques, our EM-based three-dimensional reconstruction of the DnaK-GrpE complex located DnaKSBD near DnaKNBD. This apparent discrepancy between the functional and structural results is explained by our finding that the tail region of the GrpE dimer in the DnaK-GrpE complex bends and its tip contacts DnaKSBD, whereas the DnaKNBD-DnaKSBD linker contacts the GrpE helical region. We suggest that these interactions define a more complex role for GrpE in the control of DnaK function.This work was supported in part by Spanish Ministry of Economy and Innovation Grants BFU2013-44202 (to J. M. V.), SAF2011-22988 (to O. L.), and BFU2013-47059 (to A. M.), Madrid Regional Government Grants S2013/MIT-2807 (to J. M. V.) and S2010/BMD-2316 (to O. L.), and Basque Government Grant IT709-13 (to A. M.).Peer reviewe

    Cryo-EM and the elucidation of new macromolecular structures: Random Conical Tilt revisited

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    Cryo-Electron Microscopy (cryo-EM) of macromolecular complexes is a fundamental structural biology technique which is expanding at a very fast pace. Key to its success in elucidating the three-dimensional structure of a macromolecular complex, especially of small and non-symmetric ones, is the ability to start from a low resolution map, which is subsequently refined with the actual images collected at the microscope. There are several methods to produce this first structure. Among them, Random Conical Tilt (RCT) plays a prominent role due to its unbiased nature (it can create an initial model based on experimental measurements). In this article, we revise the fundamental mathematical expressions supporting RCT, providing new expressions handling all key geometrical parameters without the need of intermediate operations, leading to improved automation and overall reliability, essential for the success of cryo-EM when analyzing new complexes. We show that the here proposed RCT workflow based on the new formulation performs very well in practical cases, requiring very few image pairs (as low as 13 image pairs in one of our examples) to obtain relevant 3D maps.We thank Dr. Llorca for his support during the acquisition of the C3b images and Dr. Shaikh for his support in the use of Spider for the RCT reconstructions. The authors would like to acknowledge economical support from the Spanish Ministry of Economy and Competitiveness through grants AIC-A-2011-0638 and BIO2013-44647-R, the Comunidad de Madrid through grant CAM (S2010/BMD-2305), as well as a postdoctoral Juan de la Cierva grant with reference JCI-2011-10185 to Javier Vargas. Vahid Abrishami is a holder of La Caixa scholarship and C.O.S. Sorzano is recipient of a Ramon y Cajal fellowship

    The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation

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    Nonsense-mediated decay (NMD) is a messenger RNA quality-control pathway triggered by SMG1-mediated phosphorylation of the NMD factor UPF1. In recent times, the RNA helicase DHX34 was found to promote mRNP remodelling, leading to activation of NMD. Here we demonstrate the mechanism by which DHX34 functions in concert with SMG1. DHX34 comprises two distinct structural units, a core that binds UPF1 and a protruding carboxy-terminal domain (CTD) that binds the SMG1 kinase, as shown using truncated forms of DHX34 and electron microscopy of the SMG1–DHX34 complex. Truncation of the DHX34 CTD does not affect binding to UPF1; however, it compromises DHX34 binding to SMG1 to affect UPF1 phosphorylation and hence abrogate NMD. Altogether, these data suggest the existence of a complex comprising SMG1, UPF1 and DHX34, with DHX34 functioning as a scaffold for UPF1 and SMG1. This complex promotes UPF1 phosphorylation leading to functional NMD
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