340 research outputs found

    Euclid space mission: a cosmological challenge for the next 15 years

    Get PDF
    Euclid is the next ESA mission devoted to cosmology. It aims at observing most of the extragalactic sky, studying both gravitational lensing and clustering over \sim15,000 square degrees. The mission is expected to be launched in year 2020 and to last six years. The sheer amount of data of different kinds, the variety of (un)known systematic effects and the complexity of measures require efforts both in sophisticated simulations and techniques of data analysis. We review the mission main characteristics, some aspects of the the survey and highlight some of the areas of interest to this meetingComment: to appear in Proceedings IAU Symposium No. 306, 2014, "Statistical Challenges in 21st Century Cosmology", A.F. Heavens, J.-L. Starck & A. Krone-Martins, ed

    Informe del encuentro de Universidades Latinoamericanas y Europeas en pedagogía hospitalaria. Red UNITWIN-UNESCO de pedagogía hospitalaria.

    Get PDF
    El presente informe da cuenta del trabajo realizado con instituciones de Educación Superior de América Latina y Europa, representantes de Ministerios de Educación y Salud, representantes de organizaciones sin fines de lucro dedicadas a la Pedagogía Hospitalaria de Latinoamérica y El Caribe

    SITUAÇÃO DE CORPOS HÍDRICOS EM BACIAS HIDROGRÁFICAS DO RIO GRANDE DO SUL SOB A PERSPECTIVA DO ÍNDICE DE CONFORMIDADE AO ENQUADRAMENTO (ICE)

    Get PDF
    O enquadramento de corpos hídricos é um importante instrumento para o acompanhamento da situação da qualidade da água. Avaliar e informar a distância na qual os principais cursos d’água se encontram em relação às metas pretendidas pelo enquadramento constitui-se em uma forma de avaliação profícua, mas normalmente pouco realizada. Esse estudo se propõe a aplicar a metodologia do Índice de Conformidade ao Enquadramento (ICE), desenvolvida pelo Canadian Council of Ministers of the Environment, em 172 estações em 19 bacias hidrográficas no Rio Grande do Sul, no período de 2015 a 2022. O estudo considerou 13 parâmetros definidos na resolução CONAMA Nº 357/2005. Os resultados indicaram que 45% das estações observadas ficaram com índice “razoável”, seguido de 41% com índice “marginal”, com resultados comprometidos principalmente pelos parâmetros cádmio, E. coli, ferro, fósforo, manganês e OD. O ICE se mostrou uma ferramenta adequada para informar de forma eficaz aos gestores e atores envolvidos a condição dos corpos hídricos de forma geral e realizar comparações entre bacias distintas

    A review of elliptical and disc galaxy structure, and modern scaling laws

    Full text link
    A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

    HPV16 E7-Dependent Transformation Activates NHE1 through a PKA-RhoA-Iinduced Inhibition of p38alpha

    Get PDF
    Background: Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/H-+(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice.Methodology: Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1.Principal Findings: We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition.Conclusions: All together these data significantly improve our knowledge concerning the basic cellular alterations involved in oncogene-driven neoplastic transformation

    Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells

    Get PDF
    INTRODUCTION: We have shown previously that overexpression of constitutively active Akt or activation of Akt caused by constitutively active Ras or human epidermal growth factor receptor-2 (HER2) confers on breast cancer cells resistance to chemotherapy or radiotherapy. As an expanded study we here report differential responses in terms of phosphorylation and activation of Akt as a result of treatment with doxorubicin in a panel of breast cancer cell lines. METHODS: The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate. RESULTS: Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase. CONCLUSION: Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy

    Calcitriol modulates the CD46 pathway in T cells

    Get PDF
    The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNc ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS

    Identification of a potent herbal molecule for the treatment of breast cancer

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.</p> <p>Methods</p> <p>To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER<sup>+</sup>)-MCF-7 and estrogen-receptor negative (ER<sup>-</sup>)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.</p> <p>Results</p> <p>PDBD inhibits cell viability of ER<sup>+ </sup>and ER<sup>- </sup>BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER<sup>+ </sup>and ER<sup>- </sup>BCa cells.</p> <p>Conclusion</p> <p>These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.</p
    corecore