640 research outputs found

    Universidad franquista: debate sobre la libertad de enseñanza (1939-1962). [Reseña]

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    Reseña de: María Ángeles SOTES ELIZALDE, Universidad franquista: debate sobre la libertad de enseñanza (1939-1962), EUNSA, Pamplona 2004, 585 pp

    Adaptive simulations, towards interactive protein-ligand modeling

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    Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations, we still lack a fast and accurate ab initio description of the binding mechanism in complex systems, available only for up-to-date techniques and requiring several hours or days of heavy computation. Such delay is one of the main limiting factors for a larger penetration of protein dynamics modeling in the pharmaceutical industry. Here we present a game-changing technology, opening up the way for fast reliable simulations of protein dynamics by combining an adaptive reinforcement learning procedure with Monte Carlo sampling in the frame of modern multi-core computational resources. We show remarkable performance in mapping the protein-ligand energy landscape, being able to reproduce the full binding mechanism in less than half an hour, or the active site induced fit in less than 5 minutes. We exemplify our method by studying diverse complex targets, including nuclear hormone receptors and GPCRs, demonstrating the potential of using the new adaptive technique in screening and lead optimization studies.We thank Drs Anders Hogner and Christoph Grebner, from AstraZeneca, and Jorge Estrada, from BSC, for fruitful discussions and feedback on the manuscript. We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by the CTQ2016-79138-R grant from the Spanish Government. D.L. acknowledges the support of SEV-2011-00067, awarded by the Spanish Government.Peer ReviewedPostprint (published version

    Stem Cells for Modeling Human Disease

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    Human pluripotent stem cells (PSCs) in the form of human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) are capable of growing indefinitely in vitro, maintaining their capacity to differentiate into the three primary germ layers: mesoderm, endoderm and ectoderm. Different protocols have been developed to differentiate PSCs into almost any cellular type with different degree of success. This technology has allowed scientists to use patient‐derived iPSCs to study the physiopathology of the disease by analyzing the phenotype of the cells derived from these iPSCs. However, control iPSCs obtained from healthy individuals will always have different genomic environment than patient\u27s iPSCs, making it difficult the interpretation of the cells phenotype. The recent appearance of specific nucleases [zinc‐finger nucleases (ZFNs), the transcription activator‐like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)] has made it possible to edit the genome of PSCs. We can now generate syngeneic hESCs or iPSCs harboring the desired mutation and comparing the emerging cells with those derived from genetically identical PSCs that will differ only in the mutated gene. In this chapter, we summarize the progress made in this field and discuss the different approaches that have been used recently for the generation of syngeneic human pluripotent cellular models for different pathologies

    The presentation of Catalan universities' linguistic reality to a transnational audience

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    This article seeks to explore critically the discourse strategies used by three Catalonian universities on their English-medium websites, directed at (prospective) transnational students, investigating how their higher education (HE) linguistic environments are portrayed. In recent decades, Catalan regained its status of lingua academica alongside Spanish; the use of Catalan in HE is regarded as vital for its long-term sustainability. In this context, efforts to attract transnational students jar with concerns raised about the hegemonic dominance of English as an academic lingua franca. After reviewing salient themes in the literature on the changing landscape of HE in Europe, we describe the linguistic and sociopolitical context of Catalonia in particular, and adopt Fairclough's three-stage discourse analysis framework to our text analysis. Texts are described and considered in terms of how they can be seen to either reproduce or challenge these emergent themes. Results show that the websites identify English as the world's undisputed academic lingua franca, and a linguistic gateway to international success. Simultaneously, the websites focus on the social and cultural significance of their local language to its foreign audience, trying to escape the risk of cultural and linguistic harmonisation that has been denounced in English as a Medium of Instruction (EMI) in other comparable contexts

    Combined effect of salinity and led lights on the yield and quality of purslane (Portulaca oleracea l.) microgreens

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    The present work aims to explore the potential to improve quality of purslane microgreens by combining water salinity and LED lighting during their cultivation. Purslane plants were grown in a growth chamber with light insulated compartments, under different lighting sources on a 16 h d-1 photoperiod\u2014fluorescent lamps (FL) and two LED treatments, including a red and blue (RB)) spectrum and a red, blue and far red (RB+IR) LED lights spectrum\u2014while providing all of them a light intensity of 150 umol m-2 s-1. Plants were exposed to two salinity treatments, by adding 0 or 80 mM NaCl. Biomass, cation and anions, total phenolics (TPC) and flavonoids content (TFC), total antioxidant capacity (TAC), total chlorophylls (Chl) and carotenoids content (Car) and fatty acids were determined. The results showed that yield was increased by 21% both in RB and RB+FR lights compared to FL and in salinity compared to non-salinity conditions. The nitrate content was reduced by 81% and 91% when microgreens were grown under RB and RB+FR, respectively, as compared to FL light, and by 9.5% under saline conditions as compared with non-salinity conditions. The lowest oxalate contents were obtained with the combinations of RB or RB+FR lighting and salinity. The content of Cl and Na in the leaves were also reduced when microgreens were grown under RB and RB+FR lights under saline conditions. Microgreens grown under RB light reached the highest TPC, while salinity reduced TFC, Chl and Car. Finally, the fatty acid content was not affected by light or salinity, but these factors slightly influenced their composition. It is concluded that the use of RB and RB+FR lights in saline conditions is of potential use in purslane microgreens production, since it improves the yield and quality of the product, reducing the content of anti-nutritional compounds

    Tratamiento de las fracturas complejas de fémur mediante enclavado intramedular encerrojado de Brooker-Wills

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    Se realiza un estudio retrospectivo de 19 pacientes con fracturas complejas de fé- mur tratados mediante el clavo bloqueado de Brooker-Wills. La causa más frecuente de dichas fracturas fueron los accidentes de tráfico. Hubo lesiones asociadas en el 63% de los casos. El tiempo medio de seguimiento fue de 27 meses. Nuestros resultados han sido evaluados mediante los criteros de Thorensen, obteniendo un 84% de resultados favorables. Hubo problemas técnicos intraoperatorios en 8 pacientes, la mayoría debidos a la penetración de la cortical femoral distal por una de las aletas. Todas las fracturas consolidaron. La mayor ventaja de este clavo la encontramos en la sencillez del bloqueo distal, lo cual supone una menor exposición a la radiación y un acortamiento del tiempo quirúrgico.A retrospective study of 19 patients with complex fermoral fractures treated with the Brooker-Wills interlocking intramedullary nail is reported. The traffic-accident was the most common cause of these fractures. Associated injuries were found in 63% of cases. The mean time follow-up period was 27 months. Results were assessed according to Thorensen's criteria. We found excellent or good results in 84% of these patients. There were intraoperative technical problems without clinical complications in 8 patients, most of them due to distal femoral cortex penetration with the pins. Union occurred in all fractures. The greatest advantage of this nail comes from the easy insertion of distal pins, providings less exposition to radiation and a shorter operative tim

    Plastia sustitutiva del LCA con tendones de la pata de ganso cuadruples

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    Se han estudiado retrospectivamente 44 casos de pacientes a los que se les realizó por vía artrocóspica una plastia sustitutiva intraticular de reconstrucción del LCA, con tendones de Semitendinoso y Recto Interno antólogos, en 4 fascículos. La edad media de los pacientes fue de 25 años. Los resultados a corto plazo (2 años) obtenidos con KT-1000 a 30 Ib han sido excelente-bueno en 40 casos y aceptable en 4 casos. Cuatro casos referían sensación de inestabilidad. Los test de Lachman y Pívot-Shift fueron positivos en 3 casos. Con el test de Lysholm se obtuvo resultado excelente-bueno en 36 casos, regular en 6 y malo en 2 casos. Este tipo de plastia presenta una baja morbilidad de la zona dadora del injerto, comparativamente con la plastia HTH patelar antóloga, y sin alteración del aparato extensor.A retrospective study of 44 patients, who underwent an arthroscopically assisted ACL (anterior cruciata ligament) reconstruction with quadrupled semitendinosus/gracilis tendon autografts was performed. The mean age was 25 years. Short term outcomes of knee stability (2 years follow-up) with KT-1000 arthrometer at 30 pounds were excellent or good in 40 cases and acceptable in 4. Pain or joint swelling were not found. Instability complaints were found in 4 cases. Lachman and Pivot-shift were found positive in 3 cases. Lysholm questionnaire scores were excellent or good in 36 cases, fair in 6 cases and per in two cases, the donor site morbidity associated with hamstring harvest seems to be minimal compared with bonepatellar tendon-bone autograft without impairment of the extensor mechanism

    Reporter Assay for Endo/Lysosomal Escape of Toxin-Based Therapeutics

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    Protein-based therapeutics with cytosolic targets are capable of exhibiting their therapeutic effect once they have escaped from the endosomes or lysosomes. In this study, the reporters—horseradish peroxidase (HRP), Alexa Fluor 488 (Alexa) and ricin A-chain (RTA)—were investigated for their capacity to monitor the endo/lysosomal escape of the ribosome-inactivating protein, saporin. The conjugates—saporin-HRP, Alexasaporin and saporin-KQ-RTA—were constructed, and the endo/lysosomal escape of these conjugates alone (lack of endo/lysosomal release) or in combination with certain structurally-specific triterpenoidal saponins (efficient endo/lysosomal escape) was characterized. HRP failed in reporting the endo/lysosomal escape of saporin. Contrastingly, Alexa Fluor 488 successfully allowed the report of the process at a toxin concentration of 1000 nM. In addition, single endo/lysosome analysis facilitated the determination of the amount of Alexasaporin released from each vesicle. RTA was also successful in reporting the endo/lysosomal escape of the enzymatically inactive mutant, saporin-KQ, but in this case, the sensitivity of the method reached a toxin concentration of 10 nM. In conclusion, the simultaneous usage of Alexa Fluor 488 and RTA as reporters may provide the possibility of monitoring the endo/lysosomal escape of protein-based therapeutics in the concentration range of 10–1000 nM. View Full-Tex

    Inestabilidad lateral crónica de tobillo: hallazgos artroscópicos y resultados tras reparación mediante técnica de Karlsson

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    ObjetivoRecoger los resultados obtenidos asociando la artroscopia diagnóstico-terapéutica a la técnica propuesta por Karlsson.Material y métodoSe revisaron retrospectivamente 11 casos tratados entre diciembre de 2004 y julio de 2009 mediante cirugía artroscópica de tobillo asociada a la técnica de Karlsson. La media de edad fue de 25 años (rango 13-45). Primero se realizó la artroscopia y posteriormente el abordaje lateral para la reparación ligamentosa. El ligamento peroneo-calcáneo se reparó en los 4 casos en que se objetivó su lesión. Se valoró la funcionalidad según la escala de la American Orthopaedic Foot and Ankle Society (AOFAS) y el grado de satisfacción subjetiva. Se recogieron las complicaciones.ResultadosTras un seguimiento medio de 11 meses, valoramos 11 pacientes cuya puntuación media según la AOFAS fue de 84 puntos. La valoración subjetiva fue excelente en 7 casos, buena en 2 y mala en 2. Como complicaciones, hubo 2 casos de síndrome de dolor regional complejo (SDRC) y un paciente tuvo que ser reintervenido con técnica de Castaing II.ConclusionesConsideramos que la asociación de la artroscopia previa a la realización de la reconstrucción para el tratamiento de la inestabilidad crónica constituye una maniobra útil para el diagnóstico de patologías articulares asociadas, aportando información importante para el pronóstico funcional de la articulación.AimsThe purpose of this study is to evaluate the result of diagnostic and therapeutic arthroscopy in association with Karlsson technique.Material And MethodsBetween 2004 and 2009, 11 patients were operated by ankle arthroscopic surgery associated with Karlsson technique. The mean age was 25 years (range 13-45). Arthroscopy was performed first and secondly the lateral approach to ligament repair. Peroneal-calcaneal ligament wasn injuried and repaired in 4 cases. AOFAS scale was used for clinical and functional evaluation, and patients were asked about subjective satisfaction. Complications were recorded.ResultsAt a mean follow-up of 11 months the mean final score was 84 points on the AOFAS scale. The subjective assessment was excellent in 7 cases, good in 2 and poor in 2. There were 2 cases of CRPS and one patient was reoperated by Castaing II technique.ConclusionsWe believe that the association of arthroscopy prior to the reconstruction is useful for associated joint lesion diagnosis, providing important information for the functional prognosis of the joint
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