5,179 research outputs found

    A study of the performance of a cyclic solid-liquid reactor

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    Imperial Users onl

    Direct activation of RNA polymerase III transcription by c-Myc

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    The proto-oncogene product c-Myc has a direct role in both metazoan cell growth and division. RNA polymerase III (pol III) is involved in the generation of transfer RNA and 5S ribosomal RNA, and these molecules must be produced in bulk to meet the need for protein synthesis in growing cells. We demonstrate here that c-Myc binds to TFIIIB, a pol III-specific general transcription factor, and directly activates pol III transcription. Chromatin immunoprecipitation reveals that endogenous c-Myc is present at tRNA and 5S rRNA genes in cultured mammalian cells. These results suggest that activation of pol III may have a role in the ability of c-Myc to stimulate cell growt

    Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: implications for stem cell mitosis and centrosome dynamics

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    Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells

    Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer

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    The small GTPase Rab25 has been functionally linked to tumour progression and aggressiveness in ovarian cancer and promotes invasion in three-dimensional environments. This type of migration has been shown to require the expression of the hypoxia-inducible factor 1 alpha (HIF-1α). In this report we demonstrate that Rab25 regulates HIF-1α protein expression in an oxygen independent manner in a panel of cancer cell lines. Regulation of HIF-1α protein expression by Rab25 did not require transcriptional upregulation, but was dependent on de novo protein synthesis through the Erbb2/ERK1/2 and p70S6K/mTOR pathways. Rab25 expression induced HIF-1 transcriptional activity, increased cisplatin resistance, and conferred intraperitoneal growth to the A2780 cell line in immunocompromised mice. Targeting HIF1 activity by silencing HIF-1β re-sensitised cells to cisplatin in vitro and reduced tumour formation of A2780-Rab25 expressing cells in vivo in a mouse ovarian peritoneal carcinomatosis model. Similar effects on cisplatin resistance in vitro and intraperitoneal tumourigenesis in vivo were obtained after HIF1b knockdown in the ovarian cancer cell line SKOV3, which expresses endogenous Rab25 and HIF-1α at atmospheric oxygen concentrations. Our results suggest that Rab25 tumourigenic potential and chemoresistance relies on HIF1 activity in aggressive and metastatic ovarian cancer. Targeting HIF-1 activity may potentially be effective either alone or in combination with standard chemotherapy for aggressive metastatic ovarian cancer

    A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

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    Background. Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug–radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures. Methods. We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available. Results. In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells. Conclusions. Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug–radiation combinations for GBM

    The Occupy and Indignados movement and the importance of political context: differences between occasionals and regulars in Spain and the UK

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    In this work we look into the individuals’ reasons that led Occupy protesters to participate in this movement. We interviewed Occupy participants in the UK and Spain. We wanted to find out if the reasons that lead them to participate are the same in both countries. The context of the country where the demonstration was held was taken into account, as well as the differences there may be in the reasons for participation if we consider whether they are occasional or regular participants in collective protest actions. Using a two-by-two design defined by country of demonstration and the history of mobilisation (occasional vs. regular), our results show important differences in both factors. The study contributes to the literature, highlighting the importance of analysing the context where the demonstration takes place and which motives must be underlined in order to attract participants to protests

    La educación en las familias de origen marroquí establecidas en España: retos y dificultades.

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    El estudio que presentamos forma parte de un Proyecto de Investigación, financiado por el Ministerio de Ciencia y Tecnología, que lleva por título: “La crisis de las concepciones y valores educativos de las familias inmigrantes magrebíes establecidas en España”. El propósito de este proyecto es conocer cómo se desarrolla el proceso de socialización primaria de los menores inmigrantes marroquíes que vienen a España acompañados por sus familias, así como las dificultades que tienen éstas para desarrollar la educación familiar fuera de su país de origen. Para llevar a cabo un proyecto de estas características hemos creído conveniente analizar nuestro foco de estudio desde dos perspectivas: la de los padres y madres inmigrantes marroquíes y la de los chicos y chicas marroquíes asentados en España. Así pues, esta comunicación tiene los siguientes propósitos: a) dar a conocer los elementos que condicionan de manera más significativa el proceso de socialización primaria que han de llevar a cabo las familias inmigrantes marroquíes en España; b) comprender los valores y las concepciones socioeducativas de la educación familiar que desarrollan los padres inmigrantes marroquíes; c) y, analizar las principales dificultades que se encuentran los padres marroquíes para afrontar su tarea educativa en la sociedad receptora. Con el propósito de satisfacer estas inquietudes decidimos emprender una investigación en la que se combinaran la metodología cuantitativa y la cualitativa, pensando que de ese modo podíamos obtener una visión más global de nuestro foco de estudio.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Characterization of wind-blown sediment transport with height in a highly mobile dune (SW Spain)

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    The Valdevaqueros dune is located at one of the windiest points of Europe, where the frequent occurrence of strong easterly winds has generated a highly mobile dune. Several rotating cup anemometers in vertical array and a self-designed vertical sand trap, were placed to retain the drift sands at different heights over the surface in order to determine theoretical and actual sand transport rates in the Valdevaqueros dune system. General results show that 90% of the wind-blown sand is transported within the first 20cm above the dune crest surface. Theoretical transport rates based on different empirical formulae were 0.33 to 0.78 times the in-situ sand transport rate detected, which was 2.08·10-2kgm-1s-1 under moderate wind power (mean speed ranging from 8.4 to 17.9ms-1). Analysis of different statistical grain-size parameters helped to understand sand transport distribution at different heights

    Rasgando la Piel: Tatuajes, Cuerpos y Significados

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    La modificacion corporal mediante el tatuaje se realiza con diferentes propositos y distintas motivaciones. Esta practica es muy comun en nuestra sociedad puertorriquena; no obstante, ha sido escasamente estudiada. Como resultado de esto, se desarrollo una investigacion con los objetivos de explorar la constitucion narrativa, el cambio de significado personal y social, y la percepcion de trabajadores/as sociales que subyace a la practica de tatuarse el cuerpo. Estos aspectos fueron estudiados entre personas tatuadas, no tatuadas y trabajadores/as sociales mediante la implantacion de un diseno exploratorio. Se espera que los hallazgos encontrados logren contribuir al interes en la realizacion de futuras investigaciones sobre el tipo de estigma relacionado al tatuaje y las repercusiones sociales que trae consigo

    Análisis del comportamiento del consumidor y el proceso de decisión de compra de celulares alta gama en Piura ciudad-2019

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    La presente investigación tuvo como objetivo principal determinar la relación que existe entre los factores del comportamiento del consumidor y el proceso de decisión de compra de celulares alta gama en Piura ciudad 2019. La investigación contiene en su estructura un tipo de estudio correlacional, de diseño no experimental trasversal. La población de estudio de la investigación estuvo conformada por los pobladores de la ciudad de Piura y la muestra de la investigación estuvo compuesta por 171 individuos a los cuales se les aplico una técnica de recolección de datos. Posteriormente para recolectar datos y alcanzar los objetivos se empleó un instrumento para la recolección de datos que fue: el cuestionario, el cual fue validado por tres expertos; y para la recolección de datos se empleó el Alfa de Cronbach con el programa SPSS versión 22.00; obteniendo un resultado de 0.806 en factores del comportamiento del consumidor y un 0.816 en el proceso de decisión de compra demostrando que el instrumento es confiable. Entre las principales conclusiones se presentó que los factores del comportamiento del consumidor no tienen una relación significativa con el proceso de decisión de comprar un teléfono móvil de alta gama, sin embargo, se encontró que los factores personales son un poco más favorables que los otros factores. En general se encontró que los factores culturales, sociales, personales, y psicológicos guardan una relación muy baja y no ayudan a influenciar en la toma de decisión de compra de un teléfono celular alta gama
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