968 resultados para Gertrud von Meran, Queen of Hungary, d. 1213


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In this article we propose an exact efficient simulation algorithm for the generalized von Mises circular distribution of order two. It is an acceptance-rejection algorithm with a piecewise linear envelope based on the local extrema and the inflexion points of the generalized von Mises density of order two. We show that these points can be obtained from the roots of polynomials and degrees four and eight, which can be easily obtained by the methods of Ferrari and Weierstrass. A comparative study with the von Neumann acceptance-rejection, with the ratio-of-uniforms and with a Markov chain Monte Carlo algorithms shows that this new method is generally the most efficient.

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The mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in polycystic kidney disease (PKD). Emerging evidence suggests that phospholipase D (PLD) and its product phosphatidic acid (PA) regulate mTOR activity. In this study, we assessed in vitro the regulatory function of PLD and PA on the mTOR signaling pathway in PKD. We found that the basal level of PLD activity was elevated in PKD cells. Targeting PLD by small molecule inhibitors reduced cell proliferation and blocked mTOR signaling, whereas exogenous PA stimulated mTOR signaling and abolished the inhibitory effect of PLD on PKD cell proliferation. We also show that blocking PLD activity enhanced the sensitivity of PKD cells to rapamycin and that combining PLD inhibitors and rapamycin synergistically inhibited PKD cell proliferation. Furthermore, we demonstrate that targeting mTOR did not induce autophagy, whereas targeting PLD induced autophagosome formation. Taken together, our findings suggest that deregulated mTOR pathway activation is mediated partly by increased PLD signaling in PKD cells. Targeting PLD isoforms with pharmacological inhibitors may represent a new therapeutic strategy in PKD.

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Bicaudal-D (Bic-D), Egalitarian (Egl), microtubules and their motors form a transport machinery that localizes a remarkable diversity of mRNAs to specific cellular regions during oogenesis and embryogenesis. Bic-D family proteins also promote dynein-dependent transport of Golgi vesicles, lipid droplets, synaptic vesicles and nuclei. However, the transport of these different cargoes is still poorly understood. We searched for novel proteins that either mediate Bic-Ddependent transport processes or are transported by them. Clathrin heavy chain (Chc) co-immunopurifies with Bic-D in embryos and ovaries, and a fraction of Chc colocalizes with Bic-D. Both proteins control posterior patterning of the Drosophila oocyte and endocytosis. Although the role of Chc in endocytosis is well established, our results show that Bic-D is also needed for the elevated endocytic activity at the posterior of the oocyte. Apart fromaffecting endocytosis indirectly by its role in osk mRNA localization, Bic-D is also required to transport Chc mRNA into the oocyte and for transport and proper localization of Chc protein to the oocyte cortex, pointing to an additional,more direct role of Bic-D in the endocytic pathway. Furthermore, similar to Bic-D, Chc also contributes to proper localization of osk mRNA and to oocyte growth. However, in contrast to other endocytic components and factors of the endocytic recycling pathway, such as Rabenosyn-5 (Rbsn-5) and Rab11, Chc is needed during early stages of oogenesis (from stage 6 onwards) to localize oskmRNA correctly.Moreover,we also uncovered a novel, presumably endocytosis-independent, role of Chc in the establishment of microtubule polarity in stage 6 oocytes.

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BACKGROUND Type D (distressed) personality, the conjoint effect of negative affectivity (NA) and social inhibition (SI), predicts adverse cardiovascular outcomes, and is assessed with the 14-item Type D Scale (DS14). However, potential cross-cultural differences in Type D have not been examined yet in a direct comparison of countries. AIM To examine the cross-cultural validity of the Type D construct and its relation with cardiovascular risk factors, cardiac symptom severity, and depression/anxiety. METHODS In 22 countries, 6222 patients with ischemic heart disease (angina, 33%; myocardial infarction, 37%; or heart failure, 30%) completed the DS14 as part of the International HeartQoL Project. RESULTS Type D personality was assessed reliably across countries (αNA>.80; αSI>.74; except Russia, which was excluded from further analysis). Cross-cultural measurement equivalence was established for Type D personality at all measurement levels, as the factor-item configuration, factor loadings, and error structure were not different across countries (fit: CFI=.91; NFI=.88; RMSEA=.018), as well as across gender and diagnostic subgroups. Type D personality was more prevalent in Southern (37%) and Eastern (35%) European countries compared to Northern (24%) and Western European and English-speaking (both 27%) countries (p<.001). Type D was not confounded by cardiac symptom severity, but was associated with a higher prevalence of hypertension, smoking, sedentary lifestyle, and depression. CONCLUSION Cross-cultural measurement equivalence was demonstrated for the Type D scale in 21 countries. There is a pan-cultural relationship between Type D personality and some cardiovascular risk factors, supporting the role of Type D personality across countries and cardiac conditions.