Systemtests, Inbetriebnahme und erste Daten des AMIGA-Myon-Detektors für das Pierre-Auger-Observatorium

War früher ohne Erratum unter folgender URL bzw. Persistent Identifier registriert: http://dokumentix.ub.uni-siegen.de/opus/volltexte/2013/716/index.html urn:nbn:de:hbz:467-7168Investigating the energy region between 10^17 eV and 4 × 10^18 eV for primary cosmic particles will lead to a deeper understanding of the origin of cosmic rays. Effects of the transition from galactic to extragalactic origin are expected to be visible in this region. The knowledge of the composition of cosmic rays strongly depends on the hadronic interaction models, which are applied in the air shower reconstruction. Directly determining the number of muons from an air shower on ground level will improve the precision of the composition measurements by reducing the dependence on the models. The Pierre Auger Observatory is facing these challenges with an upgrade of the original detector setup. A denser sub-array of water Cherenkov detectors and a dedicated muon detector (MD) array constitute the AMIGA enhancement (Auger Muon and Infill for the Ground Array). Additional fluorescence telescopes constitute HEAT (High Elevation Auger Telescopes). Seven MD modules have been installed until mid 2012 in a first hexagon at the site of the Pierre Auger Observatory in Malargüe, Argentina. The corresponding readout electronics, and 19 more of these setups, were assembled and tested in Siegen to assure correct functionality. The detectors were incorporated in the trigger structure of the original surface detector (SD) array of the Pierre Auger Observatory and are now taking data synchronously. In the framework of this thesis, system tests have been developed, a pre-unitary cell (PUC) of seven modules has been successfully operated and their trigger has been synchronised with the SD trigger. First data from the MD have been analysed and have been combined with data from the SD.Die Erforschung der primären kosmischen Strahlung im Energiebereich von 10^17 eV bis 4 × 10^18 eV wird zu einem tieferen Verständnis ihrer Herkunft führen. Effekte, verursacht durch den Übergang von galaktischem zu extragalaktischem Ursprung der Strahlung, werden in diesem Bereich als beobachtbar erwartet. Die Erkenntnisse über die Zusammensetzung der kosmischen Strahlung hängen dabei stark vom hadronischen Interaktionsmodell ab, welches in der Luftschauerrekonstruktion verwendet wird. Ein direkter Nachweis der Anzahl der Myonen auf Bodenniveau in einem solchen Luftschauer wird die Präzision der Messungen zur Zusammensetzung der Strahlung verbessern, da er die bestehenden Abhängigkeiten von den Modellen reduzieren wird. Das Pierre Auger Observatorium begegnet diesen Herausforderungen mit einer Erweiterung des ursprünglichen Detektoraufbaus. Ein dichter gesetztes Detektorfeld von Wasser-Cherenkov-Detektoren und zusätzliche, spezielle Myon-Detektoren bilden die AMIGA Erweiterung (Auger Muon and Infill for the Ground Array). Zusätzliche Fluoreszenz-Teleskope bilden HEAT (High Elevation Auger Telescopes). Sieben Module des Myon-Detektors wurden bis Mitte 2012 in einem ersten Hexagon am Pierre Auger Observatorium in Malargüe in Argentinien installiert. Die dazugehörige Ausleseelektronik, und 19 weitere dieser Systeme, wurden in Siegen zusammengesetzt und getestet um korrekte Funktionalität zu garantieren. Die Module wurden in die Trigger-Struktur des bestehenden Oberflächen-Detektorfeldes eingebunden und nehmen nun Daten in einem synchronisierten Modus. Im Rahmen dieser Arbeit wurden Systemtests entwickelt, die ersten Module des Myon-Detektors erfolgreich in Betrieb genommen und ihr Trigger mit dem bestehenden Triggersystem synchronisiert. Erste resultierende Daten wurden mit den Daten des Oberflächen-Detektors kombiniert und analysiert

Specific differences in migratory function of myofibroblasts isolated from Crohn's disease fistulae and strictures

BACKGROUND: Recently we found that migration of colonic lamina propria fibroblasts in Crohn's disease patients (CD-CLPF) from inflamed mucosa is significantly reduced as compared to control-CLPF. The behavior of CD-CLPFs isolated from fistulae and strictures was now investigated in detail. METHODS: Initially migration assays for all CLPF cultures (CD-CLPF, fibrosis-CLPF, and fistula-CLPF) were performed in the modified 48-well Boyden chamber. Subsequently, for a migration assay more resembling the in vivo situation a 3D matrix model was developed. After seeding of cells into the 3D matrix the CLPF layer was wounded by an ERBIUM:YAG laser leading to circular cell rupture without effect on the extracellular matrix. RESULTS: In the modified Boyden chamber migration of fistula-CLPF was significantly reduced compared to CD-CLPF. This was correlated with a decrease in FAK-protein expression, whereas in migrating fibrosis-CLPF an increase in FAK-protein expression, -autophosphorylation and migratory potential was found. This was confirmed in the 3D matrix wounding assay: Fistula-CLPF migrated less than CD-CLPF, whereas fibrosis-CLPF migrated significantly more in the 3D matrix wounding assay. Between 1 to 36 hours incubation time fibrosis-CLPF always displayed increased migration ability as compared to CD-CLPF. In contrast, fistula-CLPF migratory potential was always below that of CD-CLPF. CONCLUSIONS: Myofibroblasts isolated from inflamed, fibrostenotic, or fistulized CD mucosa differ in their migratory potential both in the modified Boyden chamber as well as in a 3D matrix model. These different migratory behaviors could be an explanation for impaired or excess wound healing and subsequently for fistula and fibrosis formation

Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo

In this letter, we describe the design, synthesis, and structure–activity relationship of 5-anilinopyrazolo­[1,5-a]­pyrimidine inhibitors of CK2 kinase. Property-based optimization of early leads using the 7-oxetan-3-yl amino group led to a series of matched molecular pairs with lower lipophilicity, decreased affinity for human plasma proteins, and reduced binding to the hERG ion channel. Agents in this study were shown to modulate pAKT^S129, a direct substrate of CK2, in vitro and in vivo, and exhibited tumor growth inhibition when administered orally in a murine DLD-1 xenograft

Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization

In this paper we describe a series of 3-cyano-5-aryl-7-aminopyrazolo­[1,5-<i>a</i>]­pyrimidine hits identified by kinase-focused subset screening as starting points for the structure-based design of conformationally constrained 6-acetamido-indole inhibitors of CK2. The synthesis, SAR, and effects of this novel series on Akt signaling and cell proliferation <i>in vitro</i> are described

Discovery and Optimization of a Novel Series of Potent Mutant B‑Raf^V600E Selective Kinase Inhibitors

B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf^V600E kinase activity both in vitro and in vivo. Investigations into the structure–activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and pharmacokinetic profile. Compounds selectively inhibited B-Raf^V600E in vitro and showed preferential antiproliferative activity in mutant B-Raf^V600E cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf^V600E A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro