Bøger udgivet af Südwestdeutscher Verlag für Hochschulschriften AG Co. KG

This thesis describes the first systematic investigation of the relationship between lipophilicity and reactivity on the one hand and cellular accumulation and cytotoxic activity on the other hand of a new class of oxaliplatin derivatives with different substituents at position 4 of the cyclohexane ring and different leaving ligands. Furthermore, the contribution of hCTR1 and hOCT1-3 on the influx of oxaliplatin was investigated. Information regarding the influence of oxaliplatin on the expression of these transporters, as well as on their localization inside cancer cells is still limited. In contrast to the studies conducted in the past, in this study no transfected cell lines were used.

Since the dawn of evolutionary biology, it was the dream of scientists to obtain a meaningful tree of life (a phylogenetic tree). Regarding the prokaryotic universe (Bacteria and Archaea), a main question of phylogenetics is whether there exists a prokaryotic tree of life actually. Those organisms exhibit mechanisms for the direct exchange of genetic material between cells that can belong to different species (horizontal gene transfer). In this book, the GBDP framework for inferring phylogenies based on whole genomes is introduced. Furthermore, the amount of horizontal gene transfer in a common set of prokaryotic genes is investigated by using a state-of-the-art method, as well as two newly developed approaches. Additionally, a new method for species delineation is proposed that is based on the GBDP method for deriving whole genome phylogenies. In the last part of this work, several software packages are presented. CopyCat, together with AxParafit and AxPcoords, represents the first Grid-enabled software package that is optimized for large-scale cophylogenetic studies. Furthermore, MEGAN, a user-friendly software application for the analysis of metagenomic datasets is presented.

Protein microarrays are essential tools for high-throughput proteome interaction and binding kinetics analysis. Recent technical developments have resulted in approaches for the generation of protein arrays by in situ cell-free expression of DNA array templates. We combined and enhanced these ideas by creating innovative microfluidic flow cells in standard microscope slide format and such improved system efficiency, operability, robustness and controllability. An automated setup suitable for both the in situ expression as well as the interaction analysis of protein microarrays by flow-injection was designed, built and evaluated. The reflecto-interferometric principle was selected to enable high-throughput label-free imaging detection. Both, the protein microarray expression and the microarray interaction analysis could be performed sequentially in the same microfluidic flow cell - the created proteins remain in their fluidic environment and never get in contact with air. Various antibody-antigene and rabbit-sera immunization assays were proving this system to be an efficient tool for interaction screenings.