160 research outputs found

    Cribado de alto rendimiento (hts) de una librería de pequeñas moléculas para la identificación de moléculas anti-EBOV

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    Motivation: Ebola virus (EBOV) is considered as the prototypical pathogen of viral hemorrhagic fever, causing severe disease and mortality rates as high as 90%. The implementation of different High-Throughput Screening systems to avoid the use of BSL-4 facilities will promote the generation of lead molecules and so the development of new therapeutics for EBOV within the next few years. The goals of the present project are directed to the discovery of new antiviral drugs against EBOV by using HTS of different libraries of small compounds, some of which have previously been an excellent source of potent antiviral compounds, by the use of a retroviral pseudotype particle (pEBOV-GFP) carrying the EBOV glycoprotein (GP).  Methods: Retroviral pseudotypes were generated by the transfection with the HIV gag-pol plasmid, pCMV-Δ8.91, the EBOV GP expression construct, pCAGGS-EBOV, and the green fluorescence protein (GFP) reporter construct, pCSGW at a ratio of 1.1:0.5:0.75 (core:envelope:reporter). At we carryed out at the IBiS the screening of different libraries of small compounds of different nature. The libraries of small compounds to be screened were synthesized by: i) the Medicinal Chemistry Institute of Madrid (IQM-CSIC), ii) the Unit of Molecular Chemistry and Pharmacology of the Institute for Research in Biomedicine of Barcelona (IRB), and iii) the Group of Organic Chemistry at the Faculty of Pharmacy of the University of Seville. Antiviral activivity was evaluated by pEBOV-mediated GFP expression.  Results: After the evaluation of 60 compounds, only compounds 4, 10, 17, 23, 33, 34, 125, 126, 279, 284, 298, 372, 385, 414 and 42 showed a significant (> 50%) inhibition of pEBOV-GFP entry (50 µM), presenting values of cytotoxicity (CC50) greater than 100 mM, therefore considered safe. Compounds 21, 371, 82, despite showing optimal inhibition percentages at 50 µM, presented CC50 values lower than our 100 µM threshold and because of that they were excluded from further evaluations. Conclusions: Although the antiviral activity of molecules identified by these system has to be confirmed against the wild-type EBOV, it is a useful tool to identify anti-EBOV candidates that also solves the necessity of work in BSL-4 facilities. Compounds identified in this work could potentially represent strong hit compounds for the development of a treatment for the EBOV disease

    A Grammatical Approach to the Modeling of an Autonomous Robot

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    Virtual Worlds Generator is a grammatical model that is proposed to define virtual worlds. It integrates the diversity of sensors and interaction devices, multimodality and a virtual simulation system. Its grammar allows the definition and abstraction in symbols strings of the scenes of the virtual world, independently of the hardware that is used to represent the world or to interact with it. A case study is presented to explain how to use the proposed model to formalize a robot navigation system with multimodal perception and a hybrid control scheme of the robot. The result is an instance of the model grammar that implements the robotic system and is independent of the sensing devices used for perception and interaction. As a conclusion the Virtual Worlds Generator adds value in the simulation of virtual worlds since the definition can be done formally and independently of the peculiarities of the supporting devices

    Split-range control for improved operation of solar absorption cooling plants

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    This paper proposes the first application of a split-range control technique on a concentrating solar collector to improve an absorption plant production. Solar absorption plants have solar power availability in phase with cooling demand under design conditions. Thus, it is a powerful cooling technology in the context of renewable energy and energy efficiency. These plants need control systems to cope with solar irradiance intermittency, reject irradiation disturbances, manage fossil fuels backup systems and dump closed-loop thermal-hydraulic oscillations. In this work, control techniques are proposed and simulated in an absorption plant in Spain. The plant consists of a concentrating Fresnel solar collector connected to an absorption chiller. The objectives are to operate with 100% renewable solar energy and avoid safety defocus events while reducing temperature oscillations and control actuators effort. Firstly, the current available plant controllers are defined, then two modifications are proposed. The first modification is a split-range controller capable of manipulating both flow and defocus of the Fresnel collector, the second modification is a PI controller to substitute the original chiller on-off controller. The results compare, through validated models, the different control systems and indicate that using both proposed controllers reduces 94% of the sum of actuators effort and 43% of the integral of absolute set-point tracking error compared to the plant's factory pre-set controllers. The suggested controllers increase 66% of energy production and 63% of exergy production. Besides, the split-range technique can be extended to any concentrating solar collector control.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Finance Code 001Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 304032/2019–0Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal de Investigación (AEI) PID2019-104149RB-I00/10.13039/501100011033Consejo Europeo de Investigación (ERC) OCONTSOLAR 78905

    Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma

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    Altres ajuts: This work was supported by grants from Institut Català d'Oncologia (ICO), Instituto de Salud Carlos III (RTICC-RD12/0036/0016 and RD12/0036/0027; PI11/00740 and PI14/00647), Fundació A. BOSCH, and ajuts predoctorals VHIR.Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal (eRMS) and alveolar (aRMS). Among the cellular heterogeneity of tumors, the existence of a small fraction of cells called cancer stem cells (CSC), thought to be responsible for the onset and propagation of cancer, has been demonstrated in some neoplasia. Although the existence of CSC has been reported for eRMS, their existence in aRMS, the most malignant subtype, has not been demonstrated to date. Given the lack of suitable markers to identify this subpopulation in aRMS, we used cancer stem cell-enriched supracellular structures (spheres and holoclones) to study this subpopulation. This strategy allowed us to demonstrate the capacity of both aRMS and eRMS cells to form these structures and retain self-renewal capacity. Furthermore, cells contained in spheres and holoclones showed significant Hedgehog pathway induction, the inhibition of which (pharmacologic or genetic) impairs the formation of both holoclones and spheres. Our findings point to a crucial role of this pathway in the maintenance of these structures and suggest that Hedgehog pathway targeting in CSC may have great potential in preventing local relapses and metastases

    SHARDS: A global view of the star formation activity at z~0.84 and z~1.23

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    In this paper, we present a comprehensive analysis of star-forming galaxies (SFGs) at intermediate redshifts (z~1). We combine the ultra-deep optical spectro-photometric data from the Survey for High-z Absorption Red and Dead Sources (SHARDS) with deep UV-to-FIR observations in the GOODS-N field. Exploiting two of the 25 SHARDS medium-band filters, F687W17 and F823W17, we select [OII] emission line galaxies at z~0.84 and z~1.23 and characterize their physical properties. Their rest-frame equivalent widths (EWrf_{\mathrm{rf}}([OII])), line fluxes, luminosities, star formation rates (SFRs) and dust attenuation properties are investigated. The evolution of the EWrf_{\mathrm{rf}}([OII]) closely follows the SFR density evolution of the universe, with a trend of EWrf_{\mathrm{rf}}([OII])\propto(1+z)3^3 up to redshift z~1, followed by a possible flattening. The SF properties of the galaxies selected on the basis of their [OII] emission are compared with complementary samples of SFGs selected by their MIR and FIR emission, and also with a general mass-selected sample of galaxies at the same redshifts. We demonstrate observationally that the UVJ diagram (or, similarly, a cut in the specific SFR) is only partially able to distinguish the quiescent galaxies from the SFGs. The SFR-M_* relation is investigated for the different samples, yelding a logarithmic slope ~1, in good agreement with previous results. The dust attenuations derived from different SFR indicators (UV(1600), UV(2800), [OII], IR) are compared and show clear trends with respect to both the stellar mass and total SFR, with more massive and highly star-forming galaxies being affected by stronger dust attenuation.Comment: Replaced to match the accepted version (24 pages, 1 table, 17 figures). Published in ApJ, 812, 155 (2015): http://stacks.iop.org/0004-637X/812/15

    Las emociones en la enseñanza de las ciencias

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    En la primera parte del artículo, se incide en la importancia del estudio de las emociones desde la didáctica de las ciencias, así como en la necesidad de establecer programas de intervención metacognitivos y metaemocionales, tanto en el aprendizaje como en la formación del profesorado, para que alumnos y profesores puedan conocer sus emociones, controlarlas y autorregularlas. En la segunda parte, nos centramos en las emociones en el conocimiento didáctico del contenido del profesorado de ciencias, incluyendo algunos resultados tanto del diagnóstico emocional del profesorado, según distintas variables, como del programa de intervención de la Universidad de Extremadura.The first part of this communication highlights the importance of studying emotions in the context of science teaching. It also examines the need for programs of meta-emotional and metacognitive intervention in learning and teacher education that are aimed at both the future teachers'and their pupils' gaining awareness of, and then controlling and self-regulating, their emotions. The second part focuses on the role emotions play in science teachers' pædagogical content knowledge, with the presentation of some results concerning the University of Extremadura's intervention program and the emotional diagnosis of teachers.En la primera part de l'article, s'incideix en la importància de l'estudi de les emocions des de la didàctica de les ciències, així com en la necessitat d'establir programes d'intervenció metacognitivos i metaemocionales, tant en l'aprenentatge com en la formació del professorat, perquè alumnes i professors puguin conèixer les seves emocions, controlar-les i autorregularlas. En la segona part, ens centrem en les emocions en el coneixement didàctic del contingut del professorat de ciències, incloent alguns resultats tant del diagnòstic emocional del professorat, segons diferents variables, com del programa d'intervenció de la Universitat d'Extremadura

    Análisis de la acción tutorial en ingeniería y arquitectura. Gestión eficaz del tiempo

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    En este trabajo expondremos un análisis exhaustivo de como se ha desarrollado la acción tutorial en la Escuela Politécnica Superior de la Universidad de Alicante en el curso 2014/2015. El marcado carácter de voluntariedad de la acción tutorial en nuestro centro por parte de estudiantes y tutores permite que el trabajo se realice más satisfactoriamente tanto por parte de tutores como por parte de los estudiantes, puesto que han decidido seguir el plan por ello mismos y no como una imposición. Además expondremos nuestras experiencias en el desarrollo del Taller de Gestión Eficaz del Tiempo, taller desarrollado en nuestro centro bajo la tutela de la experta Nuria Alberquilla, que tiene entre otros muchos objetivos el aprendizaje y puesta en práctica de técnicas para realizar una gestión eficaz del tiempo, con un mejor equilibrio entre la vida académica y personal y la identificación de los principales factores externos e internos que influyen en los resultados obtenidos, y cómo mejorarlos

    Experiencias en la tutorización de enseñanzas técnicas

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    El PAT en la Escuela Politécnica está abierto a todos aquellos tutores que deseen formar parte del plan y también a todos los alumnos, que, voluntariamente pueden marcar la opción de participar en el plan en la matrícula, y también a aquellos que, a pesar de no marcar la opción en la matrícula, finalmente han decidido seguir el plan de acción tutorial. Esta característica de participación e inscripción voluntaria permite que el trabajo se realice más satisfactoriamente tanto por parte de tutores como por parte de los alumnos, puesto que han decidido seguir el plan por ello mismos y no como una imposición. Con este trabajo nos proponemos presentar nuestras experiencias en el desarrollo de la tutorización de nuestros estudiantes así como la evolución en el desarrollo de la tutorización por pares

    CSVS, a crowdsourcing database of the Spanish population genetic variability

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    The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variabilityworldwide. CSVS is also part of the GA4GH Beacon network.Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721European Union (EU)European Union (EU) 676559University Chair UAM-IIS-FJD of Genomic MedicineRamon Areces Foundatio

    Coordinación del Plan de Acción Tutorial en la Escuela Politécnica Superior

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    Al igual que en cursos anteriores en la Escuela Politécnica se desarrolla, promovido por el Vicerrectorado de Estudios, Formación y Calidad, coordinado desde el Instituto de Ciencias de la Educación, el Plan de Acción Tutorial (PAT) el cual está abierto a todos aquellos tutores que deseen formar parte del plan y también a todos los estudiantes, que, voluntariamente pueden marcar la opción de participar en el plan en la matrícula, y también a aquellos que, a pesar de no marcar la opción en la matrícula, finalmente han decidido seguir el plan de acción tutorial. Esta característica de participación e inscripción voluntaria permite que el trabajo se realice más satisfactoriamente tanto por parte de tutores como por parte de los estudiantes, puesto que han decidido seguir el plan por ello mismos y no como una imposición. Con este resumen nos proponemos presentar nuestras experiencias en el desarrollo del PAT de nuestro centro
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