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Future FAIR experiments have to deal with very high input rates, large track multiplicities, make full event reconstruction and selection on-line on a large dedicated computer farm equipped with heterogeneous many-core CPU/GPU compute nodes. To develop efficient and fast algorithms, which are optimized for parallel computations, is a challenge for the groups of experts dealing with the HPC computing. Here we present and discuss the status and perspectives of the data reconstruction and physics analysis software of one of the future FAIR experiments, namely, the CBM experiment.
Postface
(2015)
Enfondant l’Académie française en 1635, le cardinal de Richelieu, Premier ministre de Louis XIII, lui avait assigné deux missions : la création d’undictionnaire de langue française etl'élaboration d’une poétique, d’une théorie littéraire analogue à celles qui existaient en Italie. Assurément, il souhaitait soutenir les écrivains français et leur donner une tribune, mais cette initiative n'était cependant pas exempte de considérations politiques. Bien qu'il n'ait pas envisagé la création d’une académie artistique, Richelieu n’excluait guère, de ses préoccupations, l'art : en 1627, il rappela à Paris Simon Vouet, alors à Rome, dans l’idée de développer un art typiquement français, qui serait indépendant des influences italiennes et flamandes. Il estimait qu’un État territorial modernese définissait toutautant par son art et sa littérature que par sa langue. La fondation de l’Académie royale de peinture et de sculpture en 1648, dans le contexte tourmenté de la Fronde, par le cardinal Mazarin, successeur de Richelieu, assignait à la nouvelle institution des tâches plus complexes quoiqu'assez voisines de celles de l’Académie française. Il s'agissait non seulement de témoigner de la noblesse de la peinture et de la sculpture, mais également de prodiguer aux générations successives une formation leur assurant de réelles qualités artistiques. ...
The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is overactivated in malignant glioma and plays a key role in promoting cell survival, thereby increasing the acquired apoptosis resistance of these tumors. Here we investigated the STAT3/myeloid cell leukemia 1 (MCL1) signaling pathway as a target to overcome the resistance of glioma cells to the Bcl-2-inhibiting synthetic BH3 mimetic ABT-737. Stable lentiviral knockdown of MCL1 sensitized LN229 and U87 glioma cells to apoptotic cell death induced by single-agent treatment with ABT-737 which was associated with an early activation of DEVDase activity, cytochrome c release, and nuclear apoptosis. Similar sensitizing effects were observed when ABT-737 treatment was combined with the multikinase inhibitor sorafenib which effectively suppressed levels of phosphorylated STAT3 and MCL1 in MCL1-proficient LN229 and U87 glioma cells. In analogous fashion, these synergistic effects were observed when we combined ABT-737 with the STAT3 inhibitor WP-1066. Lentiviral knockdown of the activating transcription factor 5 combined with subsequent quantitative polymerase chain reaction analysis revealed that sorafenib-dependent suppression of MCL1 occurred at the transcriptional level but did not depend on activating transcription factor 5 which previously had been proposed to be essential for MCL1-dependent glioma cell survival. In contrast, the constitutively active STAT3 mutant STAT3-C was able to significantly enhance MCL1 levels under sorafenib treatment to retain cell survival. Collectively, these data demonstrate that sorafenib targets MCL1 in a STAT3-dependent manner, thereby sensitizing glioma cells to treatment with ABT-737. They also suggest that targeting STAT3 in combination with inducers of the intrinsic pathway of apoptosis may be a promising novel strategy for the treatment of malignant glioma.
Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.
Different types of altruistic behavior, namely help-giving, altruistic punishment, and moral courage, are identifiable and distinguishable in the literature, but little is known how they relate to each other. This is significant because understanding altruism and other-regarding behavior is important in the attempt to solve global problems of overpopulation and depletion of natural resources. Understanding the helping forms of altruism (help-giving and sharing) can be helpful, for example, when designing donation collections or recruiting volunteers. Understanding the punitive forms of altruism (moral courage and altruistic punishment) gives valuable insight on individuals participating in campaigns where there is a need to take action, for example, against polluters or governments that violate human rights. The empirical evidence presented in this dissertation demonstrate individual and cultural differences in help-giving, altruistic punishment, and morally courageous behavior. The willingness to engage in the three types of altruistic behaviors relate differently to subjectively preferred thinking style and to personality traits, both in real-life and on the Internet. The divergencies are observable between Eastern (Indian) and Western (German) cultures, where the overlap of oneself and other individuals is experienced in different levels.
The processing of pain undergoes several changes in aging that affect sensory nociceptive fibers and the endogenous neuronal inhibitory systems. So far, it is not completely clear whether age-induced modifications are associated with an increase or decrease in pain perception. In this study, we assessed the impact of age on inflammatory nociception in mice and the role of the hormonal inhibitory systems in this context. We investigated the nociceptive behavior of 12-month-old versus 6–8-week-old mice in two behavioral models of inflammatory nociception. Levels of TRP channels, and cortisol as well as cortisol targets, were measured by qPCR, ELISA, and Western blot in the differently aged mice. We observed an age-related reduction in nociceptive behavior during inflammation as well as a higher level of cortisol in the spinal cord of aged mice compared to young mice, while TRP channels were not reduced. Among potential cortisol targets, the NF-κB inhibitor protein alpha (IκBα) was increased, which might contribute to inhibition of NF-κB and a decreased expression and activity of the inducible nitric oxide synthase (iNOS). In conclusion, our results reveal a reduced nociceptive response in aged mice, which might be at least partially mediated by an augmented inflammation-induced increase in the hormonal inhibitory system involving cortisol.
Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
(2015)
Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e. particles that have grown to diameters of 10 and 15nm following nucleation, and measure their water uptake. Water uptake constrains their chemical composition. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) experiments performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from α-pinene oxidation. The hygroscopicity parameter Κ decreased with increasing particle size indicating decreasing acidity of particles. No clear effect of the sulfuric acid monomer concentrations on the hygroscopicities of 10nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15nm particles sharply decreased with decreasing sulfuric acid monomer concentrations. In 20 particular, when the concentrations of sulfuric acid was 5.1 x 106 molecules cm exp -3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured Κ of 15nm particles was 0.3 ± 0.01 close to the value reported for dimethylamine sulfate (DMAS) (Κ DMAS ~ 0.28). Furthermore, the difference in Κ between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The Κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth already at 10nm sizes.
In den letzten drei Jahrzehnten haben sich die politischen, ökonomischen, sozialen und kulturellen Strukturen unserer Welt auf verschiedenen Ebenen radikal verändert. Das Interesse am Islam ist nicht nur in wissenschaftlichen Arbeiten und Zeitschriften gestiegen, sondern auch in allen anderen westlichen Medien. Dieses Interesse wurde unter Anderem durch die Islamisch-Iranische Revolution von 1979, die Fatwa gegen den Buchautor von „Die satanischen Verse“ Salman Rushdie 1989, die Golfkriege Anfang der 90er Jahre, den Balkankonflikt als auch die Einwanderung von Migranten mit islamischem Hintergrund in Europa gefördert...
The role of social groups in making historical events succeed takes shape according to two important factors: Their ability to change and the kind of their contribution to the development of that change in a way or another. The role of social groups especially emerges at times of revolutions and their subsequent changes on the political, socioeconomic and even intellectual levels. The most active and capable group to achieve change is the group of youth and students. In the revolutionary movements in Latin America, for instance, students prominently contributed to the fall down of long-lasting totalitarian dictatorships such in Chile, Brazil and Argentina. In the Arab uprisings in 2010-2011, students‘ roles varied from one country to another based on three axes of context, networks and contentious practices. This article expands on the role of Egyptian student movement in thriving for change despite the intensified restrictions by the state and how it continued its protest under repressive circumstances as a political actor...