Der Large Hadron Collider am CERN bei Genf, Schweiz, wird Protonen bei einer Schwerpunktsenergie von 14 TeV und Luminosität von 1034 cm-2 s-1 alle 25 ns kollidieren. Dabei enstehen per Strahkreuzung ca. 20 zusätzliche Proton-Proton-Wechselwirkungen, deren überlagerte Signale vom ATLAS Detektor gemessen werden. Diese Ereignisse müssen möglichst präzise verstanden werden, um neuartige physikalische Phänomene entdecken zu können, aber auch um das Verständnis bereits bestehender Konzepte zu verbesssern, die diese weichen Wechselwirkungen quantitativ beschreiben. In Monte-Carlo (MC) Generatoren wie EPOS, PHOJET und PYTHIA sind solche phänomenologischen Modelle weicher Prozesse eingebunden. Allerdings sind sie vielfach parametrisierbar und müssen mit experimentellen Daten angepasst werden. In dieser Arbeit wurde eine neue Methode entwickelt die auf genetischen Algorithmen und verteilten Analysetechniken basiet, um diese MC-Parameter anzupassen. Sie stellt einen alternativen Ansatz zu derzeit verfügbaren Methode wie PROFESSOR dar mit dem Vorteil, dass die Suche nach geeigneten Modellparametern automatisiert ist. Die Ergebnisse wurden mit den MC-Generatoren EPOS und PHOJET und Daten von UA5 CDF, CMS und ATLAS verglichen, wobei eine Reihe von charakteristischen Verteilungen untersucht wurde. Auch Vorhersagen für LHC-Energien werden auf Generatorlevel wie auch nach kompletter ATLAS-Detektor-Simulation präsentiert. Datenvergleiche beveoruzugen nicht eindeutig eines der in die Generatoren imple- mentierten Modelle, jedoch beschreibt EPOS die untersuchten Verteilungen etwas besser. Neue Daten von ATLAS und CMS zeigen höhere Multiplizitäten als erwartet und einen schnelleren Anstieg der zentralen Multiplizität mit der Schwerpunktsen- ergie. / The Large Hadron Collider near Geneva Switzerland will ultimately collide protons(p) at a center-of-mass(sqrt(s)) energy of 14 TeV and 40 MHz bunch crossing rate with a luminosity of 10^34cm^-2s^-1. At each bunch crossing about 20 soft p-p interactions are expected to happen. In order to study new phenomena and improve our current knowledge of the physics these events must be understood. However, the physics of soft interactions are not completely known at such high energies. Different phenomenological models, trying to explain these interactions, are implemented in several Monte-Carlo (MC) programs such as PYTHIA, PHOJET and EPOS. Some parameters in such MC programs can be tuned to improve the agreement with the data. In this thesis a new method for tuning the MC programs, based on Genetic Algorithms (GA) and distributed analysis techniques have been presented. This method represents the first and fully automated MC tuning technique that is based on true MC distributions. It is an alternative to parametrization-based automatic tuning. This new method is used in finding new tunes for PYTHIA 6 and 8. These tunes are compared to the tunes found by alternative methods and found to be equivalent or better. Charged particle multiplicity, dN_{ch}/d\eta, Lorentz-invariant yield, p_{T} and distributions at various sqrt(s) are generated using default tunes of EPOS, PHOJET and the GA tunes of PYTHIA 6 and 8. These distributions are compared to measurements from UA5, CDF, CMS and ATLAS in order to investigate the best model available. Their predictions for the ATLAS detector at LHC energies have been investigated both with generator level and full detector simulation studies. Comparison with the data did not favor any model implemented in the generators, but EPOS is found to describe investigated distributions better. New data from ATLAS and CMS show higher than expected multiplicities and a faster rise with the sqrt(s) in central particle multiplicity.

Social anxiety disorder, also known as social phobia, is one of the most prevalent anxiety disorders, affecting 7-13% of subjects in the community at some time in their lives. Despite being eminently treatable, it remains largely under-recognised and, therefore, undertreated. The disorder is characterized by a fear of scrutiny by others, with sufferers experiencing excessive anxiety in social and performance situations. This excessive anxiety usually leads to avoidance behaviour that can severely affect normal daily living. With onset commonly occurring during childhood or adolescence, social anxiety disorder may disrupt normal patterns of development of social and personal relationships, often having a long-term impact on emotional stability in social or working life. If left untreated, the course of social anxiety disorder is frequently complicated with comorbid conditions, particularly major depression or substance abuse. This review assesses the size of the clinical problem by evaluating current and lifetime prevalence estimates, age of onset, risk factors and evolution of the clinical course; thereby providing the rationale for early recognition and prompt treatment.

The retrotransposon Ylt1 was described previously from the genome of the dimorphic fungus Yarrowia lipolytica. Remarkably, Ylt1 is currently the largest LTR retrotransposon reported from fungal genomes. However, little was known about its biology and its interactions with host genome. So, the aim of this work was the characterization of properties of Ylt1.Analysis of proteins encoded by Ylt1 (Gag protein and integrase) was carried out during this work. To enable their detection, both proteins were tagged with HA epitopes. The sizes of Gag protein and putative precursors of Gag protein and integrase were estimated, and a model for the proteolytic processing of the polyprotein of Ylt1 was proposed. It was shown that Gag protein of Ylt1 is about 2-fold larger than Gag proteins of other studied yeast retrotransposons. An analysis of Ylt1 expression was also performed. Production of the Ylt1 Gag protein under different conditions was analyzed by Western blotting. Expression of Ylt1 occurred on all tested carbon sources. The amount of Ylt1 decreased rapidly upon transition to stationary growth phase, in the presence of copper sulfate and under heat shock conditions. It is suggested that Ylt1 is expressed in actively growing cells, whereas stress conditions have a negative impact on its expression. Such expression pattern was not previously reported for other yeast retrotransposons. Activity of Ylt1 in vivo was characterized using an Ylt1 elements tagged with SUC2 gene of Saccharomyces cerevisiae. Mobilization of the marked Ylt1 element and its transposition from autonomous plasmid into host genome was observed in performed experiments. Obtained results strongly support the idea that Ylt1 is transpositionally active. Formation of tandem repeats by newly inserted Ylt1 elements was observed in several cases. It is suggested that integrase function was affected in this case, and that the integration was mediated by homologous recombination instead. Analysis of the Ylt1 insertion specificity and of the Ylt1 distribution in the genome of Y. lipolytica E150 was done. The remarkable sequence specificity of Ylt1 insertions, which is unusual for LTR retrotransposons, was revealed during this analysis. Also, it was shown that Ylt1 insertions are found mainly in intergenic regions, often at a significant distance (>500 bp) from the next reading frame. No association of Ylt1 insertions with tRNA genes was observed. Searches for Ylt1-related elements in the Y. lipolytica genome database were performed. The novel Ty3/gypsy element Tyl6 was found in the genome of Y. lipolytica E150. The sequence analysis of this element was carried out. It was shown that structural properties of Tyl6 resemble the properties of the Ty3 element of S. cerevisiae. However, two reading frames of Tyl6 (gag and pol) are separated by -1 frame-shift, which was not previously reported for retrotransposons of hemiascomycetous yeasts. Phylogenetic analysis placed Tyl6 within chromoviruses, and the Tse3 element of S. exiguus was shown to be the closest relative of Tyl6. The distribution of Tyl6 among Y. lipolytica strains was analyzed. Interestingly, the novel element was found only in strains derived from the strain YB423-12. The strains of independent origin included in the analysis were shown to be Tyl6-free. The same distribution was previously reported for the retrotransposon Ylt1 and for the DNA transposon Mutyl. Two models of the evolution of transposable elements in Y. lipolytica genome were proposed based on these results.

In der vorliegenden Arbeit untersuchten wir an einer europäischen Population ausgewählte Polymorphismen zweier Gene auf eine Assoziation zu IA. Beide Gene FIGF und ACE2 sind lokalisiert auf Chromosom Xp22 und stellen damit positionelle Kandidatengene dar, aber auch funktionell sind sie von Interesse, da sie v.a. in Prozesse des Gefäßwachstums (FIGF) und der Blutdruckregulierung (ACE2) involviert sind; Vorgänge also, die möglicherweise in die pathophysiologische Erklärung der IA Entstehung mit hineinspielen. In keinem der insgesamt neun analysierten Polymorphismen konnten wir jedoch eine signifikante Assoziation zu IA finden. Auch eine Analyse möglicher intra- und intergenetischer Haplotypen aller untersuchten Varianten erbrachte kein signifikantes Ergebnis.

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