Автоматизация доставки, установки и обновления лицензированного программного обеспечения на базе веб-сервиса UTS Marketplace

Работа посвящена проектированию и разработке информационной системы для автоматизации процессов лицензирования и доставки программного обеспечения на устройства клиентов, его своевременного обновления и контроля за его исполнением. Разрабатываемая информационная система состоит из web-сервисов, интегрируемых с сервисом цифрового распространения программного обеспечения UTS Marketplace и кроссплатформенного desktop-клиента UTS Launcher. Результаты работы позволят в значительной мере автоматизировать бизнес-процессы компании ООО "Универсальные терминал системы".The work is devoted to the design and development of an information system for automating licensing and software delivery processes to customer devices, its timely updating and monitoring of its execution. The developed information system consists of web services that are integrated with the UTS Marketplace software digital distribution service and the UTS Launcher cross-platform desktop client. The results of the work will significantly automate the business processes of the company Universal Terminal Systems LLC

Zell- und molekularbiologische Untersuchungen eines EPO-mimetischen Peptides während der präklinischen Phase der Arzneimittelentwicklung

In this doctoral thesis BB68 was identified as a potent monomeric EPO-mimetic peptide. One of the main tasks was to characterize the in vitro effects of the monomeric peptide (BB68), of the homodimeric peptide (AGEM400) and of the multimeric form AGEM400-HES. The centre of the analysis was focused on AGEM400-HES where on the average of five peptide dimers are coupled multivalent to hydroxyethylstarch (HES). AGEM400-HES showed strong EPO-mimetic effects for all investigated parameters. The effects of AGEM400-HES on proliferation, apoptosis and differentiation of hematopoietic cells were analysed and compared to the EPO-induced effects. Dependent on the cell line AGEM400-HES induced proliferation, survival and differentiation in a dose-dependent manner and with an efficacy which is comparable to that of EPO. Experiments with primary cells of bone marrow from human and monkey confirmed the results. Further on investigations of the receptor binding showed that AGEM400-HES bound specifically to the EPO-receptor and induced same signaling pathways as EPO. AGEM400-HES caused the phosphorylation of STAT5 (JAK/STAT-signaling pathway) and of ERK1/2 (Ras/Raf-signaling pathway) in hematopoietic cell lines. After the generation of antibodies against EPO, BB68 and AGEM400 it was analysed if there were any crossreactions between the different antibodies and antigens. But no crossreactions could be detected. Both mimetic peptide forms were immunological completely different from EPO. A very sensitive ELISA for detecting AGEM400 and AGEM400-HES in human serum and rat serum respectively was developed. The detectable concentration range supposable may be in a clinical relevant range and it could be used as a verification procedure for further pharmacokinetic and clinical studies. AGEM400 is a potent and a promising candidate for a novel “EPO-therapy”. The main advantages are the possibility of a chemical synthesis, the biodegradable carrier molecule (HES) and the immunological diversity to EPO. The latter is a very interesting point regarding patients who had developed antibodies against the endogenous and the recombinant protein EPO during application of EPO. A mimetic peptide could be an alternative to correct anemia in these patients

Zell- und molekularbiologische Untersuchungen eines EPO-mimetischen Peptides während der präklinischen Phase der Arzneimittelentwicklung

In this doctoral thesis BB68 was identified as a potent monomeric EPO-mimetic peptide. One of the main tasks was to characterize the in vitro effects of the monomeric peptide (BB68), of the homodimeric peptide (AGEM400) and of the multimeric form AGEM400-HES. The centre of the analysis was focused on AGEM400-HES where on the average of five peptide dimers are coupled multivalent to hydroxyethylstarch (HES). AGEM400-HES showed strong EPO-mimetic effects for all investigated parameters. The effects of AGEM400-HES on proliferation, apoptosis and differentiation of hematopoietic cells were analysed and compared to the EPO-induced effects. Dependent on the cell line AGEM400-HES induced proliferation, survival and differentiation in a dose-dependent manner and with an efficacy which is comparable to that of EPO. Experiments with primary cells of bone marrow from human and monkey confirmed the results. Further on investigations of the receptor binding showed that AGEM400-HES bound specifically to the EPO-receptor and induced same signaling pathways as EPO. AGEM400-HES caused the phosphorylation of STAT5 (JAK/STAT-signaling pathway) and of ERK1/2 (Ras/Raf-signaling pathway) in hematopoietic cell lines. After the generation of antibodies against EPO, BB68 and AGEM400 it was analysed if there were any crossreactions between the different antibodies and antigens. But no crossreactions could be detected. Both mimetic peptide forms were immunological completely different from EPO. A very sensitive ELISA for detecting AGEM400 and AGEM400-HES in human serum and rat serum respectively was developed. The detectable concentration range supposable may be in a clinical relevant range and it could be used as a verification procedure for further pharmacokinetic and clinical studies. AGEM400 is a potent and a promising candidate for a novel “EPO-therapy”. The main advantages are the possibility of a chemical synthesis, the biodegradable carrier molecule (HES) and the immunological diversity to EPO. The latter is a very interesting point regarding patients who had developed antibodies against the endogenous and the recombinant protein EPO during application of EPO. A mimetic peptide could be an alternative to correct anemia in these patients

NMR Study of Solvation Effect on the Geometry of Proton-Bound Homodimers of Increasing Size

Hydrogen bond geometries in the proton-bound homodimers of quinoline and acridine derivatives in an aprotic polar solution have been experimentally studied using H-1 NMR at 120 K. The reported results show that an increase of the dielectric permittivity of the medium results in contraction of the N center dot center dot center dot N distance. The degree of contraction depends on the homodimer's size and its substituent-specific solvation features. Neither of these effects can be reproduced using conventional implicit solvent models employed in computational studies. In general, the N center dot center dot center dot N distance in the homodimers of pyridine, quinoline, and acridine derivatives decreases in the sequence gas phase > solid state > polar solvent