178 resultados para Rif


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Nadie cuestiona que una fuente de aprendizaje es el propio ámbito de trabajo, en el que todo profesional resuelve las funciones y tareas a las que se enfrenta diariamente a partir de su formación y de su experiencia. Reconocer esta experiencia en las titulaciones de Grado es un tema aún no resuelto. Pero este reconocimiento exige un proceso de evaluación, apoyado en metodologías y herramientas fiables y válidas, a partir del cual se valide que una persona ha adquirido un determinado nivel de logro en unas competencias en el marco de una cualificación profesional determinada. A raíz de los resultados obtenidos en 2 convocatorias dirigidas al reconocimiento de la experiencia profesional en el Grado en Educación Social impartido por la UNED, este articulo lleva a cabo un análisis de carácter descriptivo y en perspectiva comparada, entre ambas ediciones (2011-12 y 2012-13), con el fin de valorar la pertinencia de este proceso y la calidad de los resultados obtenidos. Con una muestra de 421 estudiantes hemos inferido la validez del procedimiento propuesto. Además, esta realidad nos muestra cuáles son las áreas de intervención más demandadas, los puntos fuertes y débiles de estos profesionales, las competencias más y menos consolidadas de acuerdo a la titulación que se imparte, etc. Disponer de estos datos, además de favorecer el desarrollo profesional de nuestros estudiantes, aporta una información clave para perfilar mejor las competencias específicas del título, trabajar de forma coordinada y colaborativa entre el mundo académico y el profesional, a la vez que responder a un derecho de nuestros estudiantes. 

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Driving high-level transgene expression in a tumour-specific manner remains a key requirement in the development of cancer gene therapy. We have previously demonstrated the strong anticancer effects of generating abnormally high levels of intracellular NO• following the overexpression of the inducible nitric oxide synthase (iNOS) gene. Much of this work has focused on utilizing exogenously activated promoters, which have been primarily induced using X-ray radiation. Here we further examine the potential of the pE9 promoter, comprising a combination of nine CArG radio-responsive elements, to drive the iNOS transgene. Effects of X-ray irradiation on promoter activity were compared in vitro under normoxic conditions and various degrees of hypoxia. The pE9 promoter generated high-level transgene expression, comparable with that achieved using the constitutively driven cytomegalovirus promoter. Furthermore, the radio-resistance of radiation-induced fibrosarcoma-1 (RIF-1) mouse sarcoma cells exposed to 0.1 and 0.01% O2 was effectively eliminated following transfection with the pE9/iNOS construct. Significant inhibition of tumour growth was also observed in vivo following direct intratumoural injection of the pE9/iNOS construct compared to empty vector alone (P<0.001) or to a single radiation dose of 10?Gy (P<0.01). The combination of both therapies resulted in a significant 4.25 day growth delay compared to the gene therapy treatment alone (P<0.001). In summary, we have demonstrated the potential of the pE9/iNOS construct for reducing radio-resistance conferred by tumour cell hypoxia in vitro and in vivo, with greater tumour growth delay observed following the treatment with the gene therapy construct as compared with radiotherapy alone.

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BACKGROUND AIMS: Cell-based gene therapy is an alternative to viral and non-viral gene therapy. Emerging evidence suggests that mesenchymal stem cells (MSC) are able to migrate to sites of tissue injury and have immunosuppressive properties that may be useful in targeted gene therapy for sustained specific tissue engraftment. METHODS: In this study, we injected intravenously (i.v.) 1x10(6) MSC, isolated from green fluorescent protein (GFP) transgenic rats, into Rif-1 fibrosarcoma-bearing C3H/HeN mice. The MSC had been infected using a lentiviral vector to express stably the luciferase reporter gene (MSC-GFP-luci). An in vivo imaging system (IVIS 200) and Western blotting techniques were used to detect the distribution of MSC-GFP-luci in tumor-bearing animals. RESULTS: We observed that xenogenic MSC selectively migrated to the tumor site, proliferated and expressed the exogenous gene in subcutaneous fibrosarcoma transplants. No MSC distribution was detected in other organs, such as the liver, spleen, colon and kidney. We further showed that the FGF2/FGFR pathways may play a role in the directional movement of MSC to the Rif-1 fibrosarcoma. We performed in vitro co-culture and in vivo tumor growth analysis, showing that MSC did not affect the proliferation of Rif-1 cells and fibrosarcoma growth compared with an untreated control group. Finally, we demonstrated that the xenogenic MSC stably expressing inducible nitric oxide synthase (iNOS) protein transferred by a lentivirus-based system had a significant inhibitory effect on the growth of Rif-1 tumors compared with MSC alone and the non-treatment control group. CONCLUSIONS: iNOS delivered by genetically modified iNOS-MSC showed a significant anti-tumor effect both in vitro and in vivo. MSC may be used as a target gene delivery vehicle for the treatment of fibrosarcoma and other tumors

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An ideal cancer chemotherapeutic prodrug is completely inactive until metabolized by a tumour-specific enzyme, or by an enzyme that is only metabolically competent towards the prodrug under physiological conditions unique to the tumour. Human cancers, including colon, breast, lung, liver, kidney and prostate, are known to express cytochrome P450 (CYP) isoforms including 3A and 1A subfamily members. This raises the possibility that tumour CYP isoforms could be a focus for tumour-specific prodrug activation. Several approaches are reviewed, including identification of prodrugs activated by tumour-specific polymorphic CYPs, use of CYP-gene directed enzyme prodrug therapy and CYPs acting as reductases in hypoxic tumour regions. The last approach is best exemplified by AQ4N, a chemotherapeutic prodrug that is bioreductively activated by CYP3A. This study shows that freshly isolated murine T50/80 mammary carcinoma and RIF-1 fibrosarcoma 4-electron reduces AQ4N to its cytotoxic metabolite, AQ4 (T50/80 K-m = 26.7 mu M, V-max = 0.43 mu M/mg protein/min; RIF-1 K-m = 33.5 mu M, V-max = 0.42 mu M/mg protein/min) via AQM, a mono-N-oxide intermediate (T50/80 K-m = 37.5 mu M; V-max = 1.4 mu M/mg protein/min; RIF-1 K-m = 37.5 mu M; V-max = 1.2 mu M/mg protein/min). The prodrug conversion was dependent on NADPH and inhibited by air or carbon monoxide. Cyp3A mRNA and protein were both present in T50/80 carcinoma grown in vivo (RIF-1 not measured). Exposure of isolated tumour cells to anoxia (2 h) immediately after tumour excision increased cyp3A protein 2-3-fold over a 12 h period, after which time the cyp protein levels returned to the level found under aerobic conditions. Conversely, cyp3A mRNA expression showed an initial 3-fold decrease under both oxic and anoxic conditions; this returned to near basal levels after 8-24 h. These results suggest that cyp3A protein is stabilized in the absence of air, despite a decrease in cyp3A mRNA. Such a 'stabilization factor' may decrease cyp3A protein turnover without affecting the translation efficiency of cyp3A mRNA. Confirmation of the CYP activation of AQ4N bioreduction was shown with human lymphoblastoid cell microsomes transfected with CYP3A4, but not those transfected with CYP2B6 or cytochrome P450 reductase. AQ4N is also reduced to AQ4 in NADPH-fortified human renal cell carcinoma (K-m = 4 mu M, V-max = 3.5 pmol/mg protein/min) and normal kidney (K-m = 4 mu M, V-max = 4.0 pmol/mg protein/min), both previously shown to express CYP3A. Germane to the clinical potential of AQ4N is that although both normal and tumour cells are capable of reducing AQ4N to its cytotoxic species, the process requires low oxygen conditions. Hence, AQ4N metabolism should be restricted to hypoxic tumour cells. The isoform selectivity of AQ4N reduction, in addition to its air sensitivity, indicates that AQ4N haem coordination and subsequent oxygen atom transfer from the active-site-bound AQ4N is the likely mechanism of N-oxide reduction. The apparent increase in CYP3A expression under hypoxia makes this a particularly interesting application of CYPs for tumour-specific prodrug activation.

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The Cederberg Mountains (Western Cape Province, South Africa) are located within the Fynbos Biome, which exhibits some of the highest levels of species richness and endemism in the world. The region's post-glacial vegetation history, however, remains largely unknown. Presented here are high resolution pollen and microcharcoal records spanning the last 15,600 years obtained from the De Rif rock hyrax midden from the Driehoek Valley of the central Cederberg. In this region, previous pollen studies have shown muted variability in vegetation community composition during periods of globally marked climatic variability (e.g. the last glacial-interglacial transition). In our record, however, significant changes in vegetation composition are apparent. Most notably, they indicate a shift from ericaceous/restioid fynbos (present from 15,600 to 13,300 cal yr BP) to a brief, but prominent, development of proteoid fynbos at the beginning of the Holocene around 11,200 cal yr BP. This vegetation shift is associated with increased moisture at the site, and coincides with reduced fire frequency as indicated by the microcharcoal record. At 10,400 cal yr BP, there is a marked reduction in Protea-type pollen, which is replaced by thicket, characterised by Dodonaea, which became the dominant arboreal pollen type. This shift was likely the result of a long relatively fire-free period coupled with warmer and wetter climates spanning much of the early Holocene. A brief but marked decrease in water availability around 8500-8000 cal yr BP resulted in the strong decrease of Dodonaea pollen. The vegetation of the mid- to late Holocene is characterised by the increased occurrence of Asteraceae and succulent taxa, suggesting substantially drier conditions. These data give unprecedented insight into the vegetation dynamics across a period of substantial, rapid climate change, and while they confirm the presence of fynbos elements throughout the last 15,600 years, the results highlight significant fluctuations in the vegetation that were triggered by changes in both climate and fire regimes. (C) 2013 Elsevier B.V. All rights reserved.

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Ressenya del llibre Répertoire des Thèses universitaires réalisées sur les Montagnes Rifaines (Maroc) en Français, Espagnol, Anglais et Arabe. Obra de caràcter bibliogràfic que recopila 556 tesis doctorals i memòries de 3r cicle produïdes, entre altres, a Marroc, França, Espanya, Regne Unit, Holanda, Bèlgica, Suïssa, Egipte, Algèria, Estats Units, etc., i referides a la zona nord del Marroc de les que 396 són en francès, 81 en àrab, 46 en castellà, 32 en anglès i 1 en català

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Ressenya del llibre Urbanisation et urbanisme dans les montagnes rifaines (Maroc). L’obra tracta sobre la urbanització i l’urbanisme al Marroc, zona caracteritzada per la complexitat i les problemàtiques espacials, econòmiques, socials, mediambientals, legals, etc., que comporta l’explosió urbana que ha experimentat aquest país, especialment la segona meitat del segle XX

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Se presentan 100 t??tulos que configuran una selecci??n de libros para ni??os y j??venes de la literatura catalana, escogidas por su indudable calidad literaria con una pretensi??n de proponer la lectura de 100 obras recomendables para los lectores mas j??venes, entre muchas que se podr??an a??adir. En esta selecci??n han participado Josep M. Aloy, Ramon Bassa, Teresa Colomer, Pere Mart?? y Beltran, Pep Molist, Joan Portell, Miquel Ray?? y Caterina Valriu, personas de reconocido prestigio en el mundo de la literatura infantil y juvenil. En este texto se encuentran 50 de los 100 t??tulos seleccionados y en la pr??xima edici??n se presentan los siguientes 50.

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Resumen tomado parcialmente de la innovación. Se completa con una carpeta de fichas didácticas para el alumnado

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Resumen de la revista en catalán

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Resumen en catalán del autor

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Resumen de la revista en catalán. Este artículo forma parte del monográfico 'Coneixement de la ciutat'