Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0 ± 0.1 fold increase in cell migration (P < .01; n = 7). Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2 ± 0.1 fold induction at 0.1 µmol/L ivabradine (P < .01 compared to SDF-1-treated cells, n = 7). The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect

Zu den KMK-Standards im Fach Mathematik: Exemplarische Analyse einer Beispielaufgabe für ein bundesweites Zentralabitur

Eine Beispielaufgabe zu den Prüfungsanforderungen im Abitur gemäß den ländergemeinsamen Standards der KMK wird untersucht und vor dem Hintergrund der Standards und Kompetenzen diskutiert

Технологическая подготовка производства изготовления детали "Ступица" на станках с ЧПУ

В данной выпускной квалификационной работе рассмотриваются вопросы технологической подготовки производства детали "Ступица".ТПП включает в себя анализ технологичности, выбор способа получения заготовки, расчет припусков на обработку детали, проектирование технологического процесса, выбор технологического оснащения, кроме того был произведен расчет технико-экономических показателей технологического процесса и социальная ответственность на производстве.In this final qualification work, the issues of technological preparation for the production of the “Hub” part are considered. The TPP includes an analysis of manufacturability, a choice of the method for producing the workpiece, calculation of allowances for processing the part, design of the technological process, the choice of technological equipment, in addition, the calculation of technical and economic indicators technological process and social responsibility in the workplace

Tachyon Condensation on the Elliptic Curve

We use the framework of matrix factorizations to study topological B-type D-branes on the cubic curve. Specifically, we elucidate how the brane RR charges are encoded in the matrix factors, by analyzing their structure in terms of sections of vector bundles in conjunction with equivariant R-symmetry. One particular advantage of matrix factorizations is that explicit moduli dependence is built in, thus giving us full control over the open-string moduli space. It allows one to study phenomena like discontinuous jumps of the cohomology over the moduli space, as well as formation of bound states at threshold. One interesting aspect is that certain gauge symmetries inherent to the matrix formulation lead to a non-trivial global structure of the moduli space. We also investigate topological tachyon condensation, which enables us to construct, in a systematic fashion, higher-dimensional matrix factorizations out of smaller ones; this amounts to obtaining branes with higher RR charges as composites of ones with minimal charges. As an application, we explicitly construct all rank-two matrix factorizations.Comment: 69p, 6 figs, harvmac; v2: minor change

Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population

<p>Abstract</p> <p>Background</p> <p>Animal experiments have shown a protective effect of vitamin C on the formation of gallstones. Few data in humans suggest an association between reduced vitamin C intake and increased prevalence of gallstone disease. The aim of this study was to assess the possible association of regular vitamin C supplementation with gallstone prevalence.</p> <p>Methods</p> <p>An observational, population-based study of 2129 subjects aged 18-65 years randomly selected from the general population in southern Germany was conducted. Abdominal ultrasound examination, completion of a standardized questionnaire, compilation of anthropometric data and blood tests were used. Data were collected in November and December 2002. Data analysis was conducted between December 2005 and January 2006.</p> <p>Results</p> <p>Prevalence of gallstones in the study population was 7.8% (167/2129). Subjects reporting vitamin C supplementation showed a prevalence of 4.7% (11/232), whereas in subjects not reporting regular vitamin C supplementation, the prevalence was 8.2% (156/1897). Female gender, hereditary predisposition, increasing age and body-mass index (BMI) were associated with increased prevalence of gallstones. Logistic regression with backward elimination adjusted for these factors showed reduced gallstone prevalence for vitamin C supplementation (odds ratio, OR 0.34; 95% confidence interval, CI 0.14 to 0.81; P = 0.01), increased physical activity (OR 0.62; 95% CI, 0.42 to 0.94; P = 0.02), and higher total cholesterol (OR 0.65; 95% CI, 0.52 to 0.79; P < 0.001).</p> <p>Conclusion</p> <p>Regular vitamin C supplementation and, to a lesser extent, increased physical activity and total cholesterol levels are associated with a reduced prevalence of gallstones. Regular vitamin C supplementation might exert a protective effect on the development of gallstones.</p

Extragalactic chemical abundances: do HII regions and young stars tell the same story? The case of the spiral galaxy NGC 300

(Abridged) We have obtained new spectrophotometric data for 28 HII regions in the spiral galaxy NGC 300, a member of the nearby Sculptor Group. The detection of auroral lines, including [OIII]4363, [SIII]6312 and [NII]5755, has allowed us to measure electron temperatures and direct chemical abundances for the whole sample. We determine for the first time in this galaxy a radial gas-phase oxygen abundance gradient based solely on auroral lines, and obtain the following least-square solution: 12+log(O/H)=8.57-0.41 R/R25, where the galactocentric distance is expressed in terms of the isophotal radius R25. The gradient corresponds to -0.077 dex/kpc, and agrees very well with the galactocentric trend in metallicity obtained for 29 B and A supergiants in the same galaxy. The intercept of the regression for the nebular data virtually coincides with the intercept obtained from the stellar data. This allows little room for depletion of nebular oxygen onto dust grains, although in this kind of comparison we are somewhat limited by systematic uncertainties, such as those related to the atomic parameters used to derive the chemical compositions. We discuss the implications of our result with regard to strong-line abundance indicators commonly used to estimate the chemical compositions of star-forming galaxies, such as R23. By applying a few popular calibrations of these indices based on grids of photoionization models on the NGC 300 HII region fluxes we find metallicities that are higher by 0.3 dex (a factor of two) or more relative to our nebular (Te-based) and stellar ones. We confirm a metallicity dependence of the `softness' parameter eta=(O+/O++)/(S+/S++), in the sense that softer stellar continua are found at high metallicity.Comment: Accepted for publication in The Astrophysical Journa