592 research outputs found

    Philosophical foundations of participatory democracy in science and technology

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    En la reflexión contemporánea sobre la ciencia, y especialmente dentro del campo de trabajo que constituyen los estudios sociales de la ciencia y la tecnología o estudios CTS, uno de los debates destacados está vinculado a la pertinencia y peculiaridades de la participación pública en el contexto de la tecnociencia (un marco en el que, a los problemas generales que se asocian con la democracia participativa, habría que añadir la problemática específica del entorno científico-tecnológico). Este trabajo explorará las preguntas generales por el quién, cuándo, de qué manera o dónde participar, a la luz de la respuesta proporcionada a la cuestión más general del por qué hacerlo. En este sentido el trabajo pondrá de manifiesto cómo buena parte del debate contemporáneo ancla sus raíces en la filosofía griega, planteando la necesidad de reconocer explícitamente esta herencia y sus implicaciones en la búsqueda de una solución adecuada a las encrucijadas de la participación en el ámbito de los problemas ambientales o la regulación energética.In contemporary reflection about science, specially in social studies of science (STS studies), one of the most important debates is related to the relevance and peculiarities of public participation in technoscientific matters (a frame where we must add the specific science and technology problems to the more general ones about participatory democracy). This article explores the general questions about who, when, how or where participate, assuming as framework the answer to the most general question about why to do it. In this sense, I will argue that contemporary debate has an important classical Greek philosophy legacy, suggesting the need to recognize this legacy and their implications in order to and adequate answers to the crossroads of citizen participation before cotemporary S&T issues such as those related to energy and the environment

    SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer

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    BACKGROUND: Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC). METHODS: Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed. Finally, high affinity SUMO binding entities-based technology were used to validate our findings in a pre-clinical mouse model and in clinical HCC. FINDINGS: We found that in human hepatoma cells under hypoxic stress, LKB1 overexpression increases cell viability and aggressiveness in association with changes in LKB1 cellular localization. Moreover, by using site-directed mutagenesis, we have shown that LKB1 is SUMOylated by SUMO-2 at Lys178 hampering LKB1 nucleocytoplasmic shuttling and fueling hepatoma cell growth. Molecular modelling of SUMO modified LKB1 further confirmed steric impedance between SUMOylated LKB1 and the STe20-Related ADaptor cofactor (STRADα), involved in LKB1 export from the nucleus. Finally, we provide evidence that endogenous LKB1 is modified by SUMO in pre-clinical mouse models of HCC and clinical HCC, where LKB1 SUMOylation is higher in fast growing tumors. INTERPRETATION: Overall, SUMO-2 modification of LKB1 at Lys178 mediates LKB1 cellular localization and its oncogenic role in liver cancer. FUND: This work was supported by grants from NIH (US Department of Health and Human services)-R01AR001576-11A1 (J.M.M and M.L.M-C.), Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C), MINECO: SAF2017-87301-R and SAF2014-52097-R integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M., respectively), BFU2015-71017/BMC MINECO/FEDER, EU (to A.D.Q. and I.D.M.), BIOEF (Basque Foundation for Innovation and Health Research): EITB Maratoia BIO15/CA/014; Instituto de Salud Carlos III:PIE14/00031, integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovacion 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M), Asociación Española contra el Cáncer (T.C.D, P·F-T and M.L.M-C), Daniel Alagille award from EASL (to T.C.D), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M and M.A), La Caixa Foundation Program (to M.L.M), Programma di Ricerca Regione-Università 2007-2009 and 2011-2012, Regione Emilia-Romagna (to E.V.), Ramón Areces Foundation and the Andalusian Government (BIO-198) (A.D.Q. and I.D.M.), ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.), MINECO:SAF2015-64352-R (P.A.), Institut National du Cancer, FRANCE, INCa grant PLBIO16-251 (M.S.R.), MINECO - BFU2016-76872-R to (E.B.). Work produced with the support of a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (M.V-R). Finally, Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). Funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

    Dimerization model of the C-terminal RNA Recognition Motif of HuR

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    In PressHuman antigen R (HuR) is a ubiquitous 32kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3′ UnTranslated Regions (UTRs) of mRNAs. In addition to binding RNA molecules, the third domain (RRM3) is involved in HuR oligomerization and apoptotic signaling. The RRM3 monomer is able to dimerize, with its self-binding affinity being dependent on ionic strength. Here we provide a deeper structural insight into the nature of the encounter complexes leading to the formation of RRM3 dimers by using Brownian Dynamics and Molecular Dynamics. Our computational data show that the initial unspecific encounter follows a downhill pathway until reaching an optimum conformation stabilized by hydrophobic interactions.I.D.-M. wishes to thank the Andalusian Government (P07-CVI-02896, P11-CVI-07216 and BIO198) for financial support.Peer reviewe

    HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs

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    HuR/ELAVL1 is an RNA-binding protein involved in differentiation and stress response that acts primarily by stabilizing messenger RNA (mRNA) targets. HuR comprises three RNA recognition motifs (RRMs) where the structure and RNA binding of RRM3 and of full-length HuR remain poorly understood. Here, we report crystal structures of RRM3 free and bound to cognate RNAs. Our structural, NMR and biochemical data show that RRM3 mediates canonical RNA interactions and reveal molecular details of a dimerization interface localized on the α-helical face of RRM3. NMR and SAXS analyses indicate that the three RRMs in full-length HuR are flexibly connected in the absence of RNA, while they adopt a more compact arrangement when bound to RNA. Based on these data and crystal structures of tandem RRM1,2-RNA and our RRM3-RNA complexes, we present a structural model of RNA recognition involving all three RRM domains of full-length HuR. Mutational analysis demonstrates that RRM3 dimerization and RNA binding is required for functional activity of full-length HuR in vitro and to regulate target mRNAs levels in human cells, thus providing a fine-tuning for HuR activity in vivo.España, MINECO BFU2015-71017España, Junta de Andalucía CVI-BIO198; P11-CVI7216 to I.D.M

    Cytochrome c signalosome in mitochondria

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    Cytochrome c delicately tilts the balance between cell life (respiration) and cell death (apoptosis). Whereas cell life is governed by transient electron transfer interactions of cytochrome c inside the mitochondria, the cytoplasmic adducts of cytochrome c that lead to cell death are amazingly stable. Interestingly, the contacts of cytochrome c with its counterparts shift from the area surrounding the heme crevice for the redox complexes to the opposite molecule side when the electron flow is not necessary. The cytochrome c signalosome shows a higher level of regulation by post-translational modifications—nitration and phosphorylation—of the hemeprotein. Understanding protein interfaces, as well as protein modifications, would puzzle the mitochondrial cytochrome c-controlled pathways out and enable the design of novel drugs to silence the action of pro-survival and pro-apoptotic partners of cytochrome c.Spanish Ministry of Science and Innovation BFU2009-07190Andalusian Government BIO198 P08-CVI-387

    Música y emociones. Propuesta de intervención en el aula

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    La finalidad de este trabajo de fin de grado (TFG), cuyo título es “Música y emociones. Propuesta de intervención didáctica en el aula de 6 años”, tiene como objetivo profundizar en la importancia de la educación emocional a través del campo de la música, se abordarán los contenidos musicales desde un punto de vista lúdico, educativo y emocional ya que el desarrollo emocional es una parte fundamental del ser humano y tiene un impacto importante en el desarrollo psicológico de los niños que marcará el resto de sus días y ayudará a fomentar las relaciones tanto intrapersonales como interpersonales.The purpose of this final degree project (TFG), whose title is “Music and emotions. Proposal of didactic intervention in the 6-year-old classroom”, aims to deepen the importance of emotional education through the field of music, musical content will be addressed from a playful, educational and emotional point of view since the development Emotional is a fundamental part of the human being and has an important impact on the psychological development of children that will mark the rest of their days and help to foster both intrapersonal and interpersonal relationships.Grado en Educación Primari

    La educación emocional como medio en la mejora del clima en el aula, en 4 años

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    La finalidad de este trabajo de Fin de Grado (TFG), cuyo título es “La educación emocional como medio en la mejora del clima de aula, en 4 años.”, tiene como objetivo poner en práctica actividades de Educación Emocional donde se trabajan las competencias emocionales, en las cuales se abordan los contenidos del área I: Crecimiento en armonía, ya que a través del desarrollo emocional se fomenta el desarrollo físico, intelectual, moral, social y emocional del ser humano y tiene un impacto importante en la vida de los niños ya que marcará el resto de sus días y ayudará a fomentar las relaciones tanto intrapersonales como interpersonales, teniendo unos resultados muy positivos en el clima del aula.The purpose of this Final Degree Project (TFG), whose title is "Emotional education as a means of improving the classroom climate, in 4 years." The objective is to implement activities of Emotional Education where emotional competences are worked, in which the contents of area I: Growth in harmony are addressed, since through emotional development the physical, intellectual, moral, social and emotional development of the human being is promoted and has an important impact on the lives of children as it will mark the rest of their days and will help to promote both intrapersonal and interpersonal relationships, having very positive results in the classroom climate.Departamento de PedagogíaGrado en Educación Infanti

    Les tessel·les de vidre metàl·lic daurat de Murano emprades en mosaic; Estudi, caracterització, evolució històrica i conservació-restauració

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    Treballs Finals de Grau de Belles Arts. Facultat de Belles Arts. Universitat de Barcelona, Curs: 2019-2020, Tutor: Vila Rabella, Marta[cat] En aquest treball s’estudiarà el vidre metàl·lic daurat de Murano, des del punt de vista de la conservació i restauració, tot fent especial èmfasi, en la seva fabricació, i tècniques d’ús en mosaic i les degradacions que se’n poden derivar. Per tal de facilitar les futures intervencions en aquest tipus de material i les seves propostes d’intervenció, s’indagarà en la bibliografia disponible sobre el tema i mitjançant també la pròpia observació d’aquest material emprat en mosaic, es proposaran mètodes simples d’estudi i diagnòstic del material, ja que com és per a tots els d’aquest sector professional ben sabut, el Conservador-Restaurador gairebé mai disposa d’elevats recursos, laboratoris ni eines sofisticades de diagnosi, sinó que en nombroses ocasions ha de treballar en vers la experiència, pròpia o aliena, d’intervencions anteriors de caràcter similar i els coneixements que en tingui o als que en pugui accedir sobre el tema.[eng] The aim of this work is to study the Golden Murano Metallic Glass, from the point of view of Conservation and Restoration, with special emphasis on its manufacture, and techniques of use in mosaic and the degradations that they can derive. In order to facilitate future interventions in this type of material and its proposals for intervention, it will be an exhaustive research of the available bibliography on the subject will be investigated and through the observation of this material used in mosaic, simple methods of study and diagnosis of the material, because as is the case for all in this well-known professional sector, the Conservator-Restorer almost never has high resources, laboratories or sophisticated diagnostic tools, and finally, on many occasions has to work in verse the own or other people's experience, of previous interventions of similar nature and, of course, the knowledge that the professional has about it or to which can reach through documentary research

    Aplicación del test de Apgar para valorar la disfunción familiar en familias con niños con TDAH: protocolos de investigación

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    27 p.Objetivo: Demostrar la relación entre la disfunción familiar medida mediante el test de APGAR familiar y tener un hijo/a en edad escolar diagnosticado de TDAH. Diseño: Estudio descriptivo. Ámbito de estudio: Área urbana de Atención Primaria de Ávila durante un año. Sujetos: Niños/as de entre 6 y 14 años diagnosticados de TDAH según DSM-IV o CIE 10 pertenecientes a cuatro centros de salud de Ávila. Variables: Dependientes: Puntuación del test de APGAR Familiar. Independientes: hijo/a diagnosticado de TDAH según criterios del DSM-IV o CIE 10, tratamiento farmacológico, psicoterapia, terapia familiar, sexo y edad niño/a y padres, nivel socio económico, grupo étnico, nivel académico de los padres, tamaño y estructura familiar y ciclo vital familiar. Desarrollo: Se solicitarán los permisos necesarios. Información a los EAP. Elaboración de un protocolo y diseño de un cuaderno de recogida de datos. Reclutamiento de los pacientes por contacto telefónico con las familias y cita programada para entregar hoja de información y consentimiento informado. Entrevista individual a madre y padre y autocumplimentación del test de APGAR Familiar. Análisis de los datos obtenidos. Difusión de los resultados obtenidos. Análisis estadístico: Para la descripción de las variables cuantitativas se utilizarán las medidas de tendencia central y de dispersión, y para las variables cualitativas se utilizarán frecuencias absolutas y porcentajes. Se realizará un análisis bivariante de las variables relacionadas con la disfunción familiar. Se propone un nivel de significación estadística para p < 0.05 y el intervalo de confianza del 95%. El análisis estadístico se realizará con el paquete SPSS® v.19.0

    Centroid-Based Clustering with ab-Divergences

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    Centroid-based clustering is a widely used technique within unsupervised learning algorithms in many research fields. The success of any centroid-based clustering relies on the choice of the similarity measure under use. In recent years, most studies focused on including several divergence measures in the traditional hard k-means algorithm. In this article, we consider the problem of centroid-based clustering using the family of ab-divergences, which is governed by two parameters, a and b. We propose a new iterative algorithm, ab-k-means, giving closed-form solutions for the computation of the sided centroids. The algorithm can be fine-tuned by means of this pair of values, yielding a wide range of the most frequently used divergences. Moreover, it is guaranteed to converge to local minima for a wide range of values of the pair (a, b). Our theoretical contribution has been validated by several experiments performed with synthetic and real data and exploring the (a, b) plane. The numerical results obtained confirm the quality of the algorithm and its suitability to be used in several practical applications.MINECO TEC2017-82807-
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