Promoter classification is the task of separating promoter from non promoter sequences. Determining promoter regions where the transcription initiation takes place is important for several reasons such as improving genome annotation and defining transcription start sites. In this study, various promoter prediction methods called ProK-means, ProSVM, and 3S1C are proposed. In ProSVM and ProK-means algorithms, structural features of DNA sequences are used to distinguish promoters from non promoters. Obtained results are compared with ProSOM which is an existing promoter prediction method. It is shown that ProSVM is able to achieve greater recall rate compared to ProSOM results. Another promoter prediction methods proposed in this study is 3S1C. The difference of the proposed technique from existing methods is using signal, similarity, structure, and context features of DNA sequences in an integrated way and a hierarchical manner. In addition to current methods related to promoter classification, the similarity feature, which compares the promoter regions between human and other species, is added to the proposed system. We show that the similarity feature improves the accuracy. To classify core promoter regions, firstly, signal, similarity, structure, and context features are extracted and then, these features are classified separately by using Support Vector Machines. Finally, output predictions are combined using multilayer perceptron. The result of 3S1C algorithm is very promising.

In Zellkulturexperimenten wurden die Effekte von Simvastatin (Prodrug), Atorvastatin, Pravastatin und dem Proteasomhemmer Lactacystin suf zwei Endothelzelllinien (CPAE und Ea.hy926) und primäre vaskuläre glatte Muskelzellen (VSMCs) bezüglich ihres Verhaltens auf die Morphologie, die Proliferation, die Viabilität und die Proteasomaktivität untersucht. Sowohl die Statine als auch Lactacystin induzierten vergleichbare morphologische Veränderungen und beeinflussten die Proliferation von CPAE-Zellen. In den eigenen Versuchen konnten durch Statine induzierte Effekte durch Mevalonat revertiert werden. Die durch Lactacystin verursachten Veränderungen wurden durch Mevalonsäure nicht beeinflusst. Wie erwartet hemmte Lactacystin in den untersuchten CPAE-Zellen signifikant die proteasomale Aktivität. Im Gegensatz dazu blieb die Proteasomaktivität nach einer Statinbehandlung unbeeinflusst. Ähnliche Ergebnisse wurden auch in den Ea.hy926 und den VSMCs deutlich. Weiterhin konnte gezeigt werden, dass sogar hohe Dosen der Statine die Aktivität der gereinigten 20S Proteasomen nicht modulieren. Aus diesen Ergebnissen lässt sich schlußfolgern, dass die ähnlichen biologischen Effekte der Statine und des Lactacystins nicht über einen gemeinsamen Mechanismus der Proteasominhibition funktionieren. / The effect of simvastatin, atrovastatin and pravastatin as well as of the proteasom inhibitor beta-clasto lactacystin was studied on morphology, proliferation viability and on proteasomaö activityin two mammalian endothelial cell lines (CPAE and Ey.hy926) and in primary vascular smooth muscle cells (VSMCs). Both statins and lactacystin induced comparable morphological changes and attenuated proliferation of CPAE. Whereas the statin-induced effects were reversed by mevalonic acid, however, the lactacystin-induced alterations were not influenced by mevalonic acid. As expected, lactacystin caused a significant loss of proteasomal activity measured in the extracts of trested cells. The extracts of statin-treated CPAEs exhibited unchanged activities. This result was also confirmed in Ea.hy926 cells and in primary rat VSMCs. It is shown, that even high dosis of statins do not modulate the activity of purified human 20S proteasomes. The conclusion was that similar biological effects of statins and the well known proteasome inhibitor lactacystin in vascular cells are not caused by a common inhibitory mechanism ofaction on the proteasome.