Zugl.: Jena, Univ., Diss., 2005 u.d.T.: Schuster, Susanne: Mein Jesus ist mir alles in allen

Dissertation--Fachbereich Philosophie und Geisteswissenschaften--Berlin--Freie Universität, 2001. / Bibliogr. p. 188-194.

Zugl.: Jena, Univ., Diss., 2005 u.d.T.: Schuster, Susanne: Mein Jesus ist mir alles in allen

Thesis (doctoral)--Universität, Mannheim, 2001. / Includes bibliographical references (p. xxiv-xliii).

No description available.

No description available.

The tetrahydroisoquinoline (THIQ) core structure is explored as a steroidomimetic nucleus with attractive pharmaceutical properties. A library was synthesised employing Pomeranz-Fritsch, Pictet-Spengler, Bischler-Napieralski strategies yielding 77 final targets, substituted at every position, for biological evaluation. Complementary strategies overcame synthetic difficulties, sometimes yielding two products in a single cyclisation. Three compounds were initially tested against a panel of 19 nuclear receptors (NRs) and exhibited broad substitution-dependent activity. 2-(4-Chlorophenyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinolin-6-ol fully inhibited every NR at 100 µM, confirming the THIQ as a lead for optimisation. Compounds were evaluated for cytotoxicity against 60 cell lines by the NCI (USA), exhibiting moderate to insignificant cytotoxicity. Three compounds showed ca. 30-90% of average growth inhibition and were selected for a five dose test. Off-target evaluation highlighted compounds with activity against glucagon-like peptide 1 secretion, calcitonin gene-related peptide receptor antagonism and with >100% inhibition against the metabotropic glutamate receptor 2. Estrogen receptor-related receptor α (ERRα), a constitutively active orphan NR, is a hormone-dependent cancer target and diethylstilboestrol (DES), a known inverse agonist, possesses similarities to THIQs. THIQs tested against ERRα revealed no general SAR rules, but showed a lower degree of efficacy in a commercial TR-FRET assay, with 1-benzyl-2-(4-chlorophenyl)-4-methyl-1,2,3,4-tetrahydroisoquinolin-6-ol showing 79% efficacy at 100 µM as an inverse agonist, being more active than DES (64% at 100 µM). Inhibition of steroidogenic enzymes like 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is an emerging approach for the treatment of HDBC, compared to other current clinical strategies. THIQs evaluated against 17β-HSD1 showed good activity in both whole cell and cell lysate assays, with the best inhibitor, 2-(4-chlorophenyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinolin-6-ol, possessing an IC50 value of 336 nM. The value of THIQ as a drug-like steroidomimetic scaffold is thus established and this work reveals straightforward strategies to optimise potency and selectivity for a range of potential targets by structural and stereochemical iteration.

Zugl.: Jena, Universiẗat, Diss., 2007/08.

On January 29-30, 2008 a squall line of thunderstorms moved through the Ohio Valley resulting in four deaths and one injury. Such events highlight the importance of accurate forecasting for public safety. Mesoscale Modeling plays an important role in any forecast of a potential squall line. The focus of this study was to examine the performance of several parameterization scheme combinations in the Weather Research and Forecasting Model version three (WRF) as they related to this event. These examinations included cloud microphysics (WRF Single-Moment 3-class, 6-class, and Goddard), cumulus parameterization (Kain-Fritsch and Bets-Miller-Janjic) and planetary boundary layer schemes (Yonsei-University and Mellor-Yamada-Janjic). A total of 12 WRF simulations were conducted for all potential scheme combinations. Data from the WRF simulations for several locations in south central Kentucky were analyzed and compared using Kentucky Mesonet observations for four locations: Bowling Green, Russellville, Murray and Liberty, KY. A fine model resolution of 1 km was used over these locations. Coarser resolutions of 3 km and 9 km were used on the outer two domains, which encompassed the Ohio and Tennessee Valleys. The model simulation performance was assessed using established statistical measures for the above four locations and by visually comparing the North American Regional Reanalysis dataset (NARR) along with modeled simulations. The most satisfactory scheme combination was the WRF Single-Moment 3-class Microphysics scheme, Kain-Fritsch cumulus parameterization scheme and Yonsei University scheme for the planetary boundary layer. The planetary boundary layer schemes were noted to have the greatest influence in determining the most satisfactory model simulations. There was limited influence from different selections of microphysics and cumulus parameterization schemes. The preferred physics parameters from these simulations were then used in six additional simulations to analyze the affect different initialization data sets have with regards to model output. Data sets used in these simulations were the Final Operational Analysis global data, North American Regional Reanalysis (3 and 6 hour) and the North American Mesoscale Model at 1, 3 and 6 hour timesteps, for a total of six simulations. More timesteps or an increase in model resolution did not materially improve the model performance.

This thesis focuses on soldering technology in microelectronics. It describes in detail the basic ways of soldering and repairs in electronics. This piece of work shows the principles of technological equipment for bulk soldering and used repairing devices. In the theoretical part of this work there are also briefly described the packages for integrated circuits that were used in the practical part of the thesis. The practical part of the thesis deals with setting of the heat profiles for hot air repair station Fritsch Mikroplacer for LQFP64, SOIC16, TSSOP14, QFN16 and DSBGA5 packages. The heat profiles for assembly and disassembly of the particular types of the packages on designed and manufactured test printed circuit board were set and tested. The resulting heat profiles are compared with the recommended heat profile of an ordinary solder paste SnAg3Cu0,5 which was used for the test. This thesis can serve as an aid for the further settings of heat profiles in other types of packages not only on Fritsch Mikroplacer devices, but also on other repairing devices of this type.