Glutathione syntethase (GS) is an enzyme that belongs to the ATP-grasp superfamily and catalyzes the second step in the biosynthesis of glutathione. GS has been purified and sequenced from a variety of biological sources; still, its exact mechanism is not fully understood. Four highly conserved residues were identified in the binding site of human GS. Additionally, the G-loop residues that close the active site during catalysis were found to be conserved. Since these residues are important for catalysis, their function was studied computationally by site-directed mutagenesis. Starting from the reported crystal structure of human GS, different conformations for the wild type and mutants were obtained using molecular dynamics technique. The key interactions between residues and ligands were detected and found to be essential for enzyme activity.

In recent years, there has been an upsurge in medical research assessing the therapeutic benefits of probiotic bacteria and growing commercial interest in food fortification with these bacteria. Probiotic bacteria such as L. acidophilus are known to be predominant Lactobacilli species in the intestinal tract of healthy humans and suggested to provide clinical health benefits such as enhancement of immunity against intestinal infections, prevention of diarrhea and hypercholesterolaemia and improvement in lactose utilization. Many studies have demonstrated the possibility of incorporating probiotic bacteria in an ice cream matrix and shown its viability can be maintained throughout the shelf life of the ice cream. However, there is limited information about the protective effect of ice cream on viability of incorporated probiotic bacteria during simulated gastric digestion using an in vitro dynamic model stomach. In phase one of this study, a preliminary study was conducted to determine the effect of air addition on the viability of L. acidophilus La-5. This was done by manufacturing low fat (4%) non-fermented ice cream mix supplemented with L. acidophilus La-5 to yield an initial population of 107cfu/g. The mix was processed with 60% and 100% overrun (OR) and stored at -10ᵒC for 90 days. The effect of air addition at different levels was tested post freezing and every 30 days throughout its shelf life of 90 days. The results showed less than one log reduction in the viable counts of L. acidophilus La-5 for both samples incorporated with 60% and 100% OR after freezing and the number of viable cells did not differ significantly (p>0.05) from day 1 to day 90. In phase two of this study, a 22 full factorial experimental design was used to evaluate whether the viscous nature of ice cream mix plays an important role in improving the survivability of L. acidophilus La-5 during simulated digestion against low pH and presence of mechanical shear and to determine whether initial inoculation level has any effect on the viability of L. acidophilus La-5 at the end of 2 hr simulated digestion. Non-fermented low fat (5%) ice cream mixes with high and low viscosity were produced by changing the amount of stabilizer/emulsifier blend and each of the two mixes were supplemented with two levels of L. acidophilus La-5 to obtain an initial population of 108cfu/g and 106cfu/g before freezing. These mixes were frozen with 60% overrun. The ice cream samples were digested for 2 hr in an in vitro model stomach called Human Gastric Simulator (HGS). This model included factors such as gastric secretions, mechanical shearing due to peristaltic contractions and temperature and pH control. No significant effect (p>0.05) of different levels of viscosity on the survivability of L. acidophilus La-5 was found during and at the end of 2 hr simulated in vitro digestion, irrespective of the difference in initial inoculation level. The initial supplementation level of L. acidophilus La-5 had a significant impact (p<0.05) on its survivability during the simulated digestion of ice cream samples, irrespective of the difference in viscosity. The log survival of L. acidophilus La-5 was on an average 3.64 log cfu/g and 4.08 log cfu/g for ice cream samples supplemented with higher and lower amount of L. acidophilus La-5, respectively at the end of 2 hr. Nevertheless, this difference in overall survival was not statistically significant (p>0.05). These studies demonstrated the efficacy of low fat non-fermented ice cream in maintaining high viable numbers of L. acidophilus La-5 throughout its tested shelf life of 90 days. In addition, protective effect of ice cream on the viability of L. acidophilus La-5 against harsh stomach conditions was observed, but this effect was not as a result of viscosity of ice cream. It was also found that an ice cream supplemented with 106cfu/g would result in a similar overall log reduction of L. acidophilus La-5 at the end of 2 hr simulated digestion compared to an ice cream supplemented with 108cfu/g. The aggressive stomach conditions had a negative impact on the survivability of L. acidophilus La-5 during digestion of all the ice cream samples, but this detrimental effect can be reduced by incorporating L. acidophilus La-5 into an ice cream matrix which would increase the opportunity of bacteria to reach the small intestine and provide the desired health benefit.

Le but de ce travail de thèse consiste à étudier les propriétés physico-chimiques des verres chalcogénures afin de pouvoir les utiliser comme membranes de capteurs chimiques destinés pour le dosage des ions Hg²⁺. Dans un premier temps, les propriétés macroscopiques des systèmes vitreux AgY-As₂S₃ (Y = Br, I), HgS-GeS₂, AgI-HgS-As₂S₃ et AgI-HgS-GeS₂, telles que les densités et les températures caractéristiques (Tg et Tc) ont été mesurées et analysées selon les compositions des verres. Puis, dans un second temps, les propriétés de transport ont été étudiés à l'aide de la spectroscopie d'impédance complexe d'une part, ou d'autre part, par des mesures de la résistivité. Ces dernières montrent que les verres de chalcogénures dopés à l'halogénure d'argent présentent deux différents régimes de transports au-dessus du seuil de percolation xc ≈ 30 ppm : (i) domaine de percolation critique, et (ii) domaine contrôlé par modificateur. Vient ensuite la troisième partie, elle consiste à déchiffrer les relations composition/structure/propriété grâce à plusieurs études structurales. Des mesures par spectroscopie Raman, par diffraction de neutrons et de rayons X haute énergie, par diffusion des neutrons sous petits angles (SANS), ainsi que des modélisations RMC/DFT et AMID ont été réalisées. Enfin, la dernière partie de ce travail était une étude préliminaire des caractéristiques des nouveaux capteurs chimiques. Il a été consacré à l'étude des relations entre la composition et la sensibilité des membranes ainsi qu'aux limites de détection qui les définissent. / The aim of the thesis is to study the physicochemical properties of the silver halide doped chalcogenide glasses for the possibility to use them as chemical sensors for quantitative analysis of Hg²⁺ ions. First, the macroscopic properties of AgY-As₂S₃ (Y = Br, I), HgS-GeS₂, AgI-HgS-As₂S₃ and AgI-HgS-GeS₂ glassy systems such as the densities and the characteristic temperatures (Tg and Tc) were measured and analyzed according to the glass compositions. Second, the transport properties were studied using complex impedance and dc conductivity. Measurements show that the silver halide doped chalcogenide glasses exhibit two drastically different ion transport regimes above the percolation threshold at xc ≈ 30 ppm : (i) critical percolation, and (ii) modifier-controlled regimes. Third, to unveil the composition/structure/property relationships, various structural studies were carried out. Raman spectroscopy, high-energy X-ray diffraction, neutron diffraction and small-angle neutron scattering experiments, together with RMC/DFT and AMID modelling were employed. Finally, the last part was a preliminary study of the characteristics of new chemical sensors. It was devoted to study the relationship between the membranes' composition and sensitivity but also detection limits.

CDAC / The introduction of languages like High Performance Fortran (HPF) which allow the programmer to indicate how the arrays used in the program have to be distributed across the local memories of a multi-computer has not completely unburdened the parallel programmer from the intricacies of these architectures. In order to tap the full potential of these architectures, the compiler has to perform this crucial task of data partitioning automatically. This would not only unburden the programmer but would make the programs more efficient since the compiler can be made more intelligent to take care of the architectural nuances. The topic of this thesis namely the automatic data partitioning deals with finding the best data partition for the various arrays used in the entire program in such a way that the cost of execution of the entire program is minimized. The compiler could resort to runtime redistribution of the arrays at various points in the program if found profitable. Several aspects of this problem have been proven to be NP-complete. Other researchers have suggested heuristic solutions to solve this problem. In this thesis we propose a genetic algorithm namely the Hierarchical Genetic Search algorithm to solve this problem.

Epithelial ovarian cancer is the sixth most common tumor disease among women and it is the leading cause of death from all types of gynecologic malignancies. The current standart of care consist of debulking surgery followed by platinum-taxane chemotherapy. Althought some patients benefit from the treatment, most eventually experience platinum-resistance and die from this disease. Immunotherapy based on application of immune checkpoint blockers represents a new treatment strategy in different cancer malignancies. However, emerging clinical data show only limited clinical efficacy of these agents in ovarian cancer patients with objective response rates of 10-15%. Therefore there is a strong need to identify a potential biomarkers, which allows to identify the group of patients, who will benefit the most from this costly treatment. The aim of my diploma thesis was to characterize the prognostic and predictive role of the immune checkpoints within the retrospective and prospective cohort of patients with high-grade serous ovarian cancer (HGSOC). Our study follows, that the expression of PD-L1 molecule and high frequencies of PD-1+ tumor infiltrating lymphocytes (TILs) in tumor microenviroment is significantly correlated with a better prognosis of patients with HGSOC. Moreover, PD-L1 and PD-1...

Mit der „Siedlungsanlage Dresden-Strehlen“ entstand zwischen 1926 und 1928 eine der bemerkenswerten Wohnanlagen in der Stadt Dresden. Sie wurde im Auftrag der „Heimstättengesellschaft Sachsen“ GmbH -HGS- nach Entwürfen des Architekten Paul Löffler errichtet. Ergänzende Wohnbauten - zwischen 1929 und 1934 realisiert - stammen von Hans Vasak. Weiterhin sind Wohnbauten des „Allgemeinen Mietbewohnerverein“ in Dresden zu nennen. Im Zusammenhang mit der Baugeschichte dieser Siedlungsanlage wird der tragische Niedergang und eine hiermit verbundene Legendenbildung vorgestellt. Die Dokumentation umfasst 42 Seiten mit 32 Abbildungen, Bebauungsplänen, Grundrisszeichnungen und bisher nicht veröffentlichten Fotos (um 1929).

Mit der „Siedlungsanlage Dresden-Strehlen“ entstand zwischen 1926 und 1928 eine der bemerkenswerten Wohnanlagen in der Stadt Dresden. Sie wurde im Auftrag der „Heimstättengesellschaft Sachsen“ GmbH -HGS- nach Entwürfen des Architekten Paul Löffler errichtet. Ergänzende Wohnbauten - zwischen 1929 und 1934 realisiert - stammen von Hans Vasak. Weiterhin sind Wohnbauten des „Allgemeinen Mietbewohnerverein“ in Dresden zu nennen. Im Zusammenhang mit der Baugeschichte dieser Siedlungsanlage wird der tragische Niedergang und eine hiermit verbundene Legendenbildung vorgestellt. Die Dokumentation umfasst 42 Seiten mit 32 Abbildungen, Bebauungsplänen, Grundrisszeichnungen und bisher nicht veröffentlichten Fotos (um 1929).

In this work the influence of solid electrolyte additives on the gas sensing properties of tin oxide layers was investigated systematically for the first time. NASICON (NAtrium, Super Ionic CONductor, Na(1+x)Zr2SixP(3-x)O12; 0 &amp;lt;= x &amp;lt;= 3) was used as a model for solid electrolyte additives. The structure of that material is ideally suitable for studies of the correlation between material parameters and the gas sensitivity of the layers. In the NASICON structure the content of mobile Na+-ions can be varied by a factor of four resulting in a simultaneous change of the ionic conductivity sigma(Na+) by approximately three orders of magnitude without considerable structural alterations. Powders of SnO2 and NASICON (x = 0; 2.2; 3) were prepared separately by means of sol-gel routes and mixed in a volume ratio of 80/20. Pastes were prepared from these powders with different compositions and screen printed on alumina substrates with a fourfold structure of thin film gold electrode combs. Four different compositions were characterised simultaneously at elevated temperatures in various gas atmospheres. The conductivity of the layers, when measured in air, decreases considerably with increasing Na+-content in the NASICON additive. This is correlated with enhanced activation energy of the electronic conductivity. The sensitivity of the layers to polar organic molecules like R-OH (alcohols), R-HO (aldehydes) and ROOH (carboxylic acids) is highly enhanced by the NASICON additive. This is observed especially on the admixtures with NASICON of high Na+-content (x = 2.2 and x = 3). On the other hand, the sensitivity to substances with mid-standing functional groups like 2-propanol or propanone can not be enhanced by NASICON additives. Furthermore the sensitivity of these composite layers to CO, H2, NH3, methane, propane, propene and toluene (all exposed as admixtures with air) is lower than the sensitivity of pure SnO2-layers. These observations are well correlated with the results of gas consumption measurements on SnO2/NASICON powders by means of FTIR spectroscopy. In spite of the lack of surface analytical data, a model of surface chemical gas reactions based on a triple phase boundary (SnO2/NASICON/gas atmosphere) was developed, which explains the experimental observations qualitatively. It is assumed that the decrease of the electronic conductivity as observed in the presence of NASICON additives with increasing Na+-content is due to an enhanced electron depletion layer. This is formed in the SnO2 grains by Na+/e- interactions across the SnO2/NASICON-interface. The enormous enhancement of the sensitivity to polar organic molecules may be due to specific nucleophilic interactions with the Na+-ions and coupled Na+/e--interactions at the triple phase reaction sites.

In this work the influence of solid electrolyte additives on the gas sensing properties of tin oxide layers was investigated systematically for the first time. NASICON (NAtrium, Super Ionic CONductor, Na(1+x)Zr2SixP(3-x)O12; 0 &amp;lt;= x &amp;lt;= 3) was used as a model for solid electrolyte additives. The structure of that material is ideally suitable for studies of the correlation between material parameters and the gas sensitivity of the layers. In the NASICON structure the content of mobile Na+-ions can be varied by a factor of four resulting in a simultaneous change of the ionic conductivity sigma(Na+) by approximately three orders of magnitude without considerable structural alterations. Powders of SnO2 and NASICON (x = 0; 2.2; 3) were prepared separately by means of sol-gel routes and mixed in a volume ratio of 80/20. Pastes were prepared from these powders with different compositions and screen printed on alumina substrates with a fourfold structure of thin film gold electrode combs. Four different compositions were characterised simultaneously at elevated temperatures in various gas atmospheres. The conductivity of the layers, when measured in air, decreases considerably with increasing Na+-content in the NASICON additive. This is correlated with enhanced activation energy of the electronic conductivity. The sensitivity of the layers to polar organic molecules like R-OH (alcohols), R-HO (aldehydes) and ROOH (carboxylic acids) is highly enhanced by the NASICON additive. This is observed especially on the admixtures with NASICON of high Na+-content (x = 2.2 and x = 3). On the other hand, the sensitivity to substances with mid-standing functional groups like 2-propanol or propanone can not be enhanced by NASICON additives. Furthermore the sensitivity of these composite layers to CO, H2, NH3, methane, propane, propene and toluene (all exposed as admixtures with air) is lower than the sensitivity of pure SnO2-layers. These observations are well correlated with the results of gas consumption measurements on SnO2/NASICON powders by means of FTIR spectroscopy. In spite of the lack of surface analytical data, a model of surface chemical gas reactions based on a triple phase boundary (SnO2/NASICON/gas atmosphere) was developed, which explains the experimental observations qualitatively. It is assumed that the decrease of the electronic conductivity as observed in the presence of NASICON additives with increasing Na+-content is due to an enhanced electron depletion layer. This is formed in the SnO2 grains by Na+/e- interactions across the SnO2/NASICON-interface. The enormous enhancement of the sensitivity to polar organic molecules may be due to specific nucleophilic interactions with the Na+-ions and coupled Na+/e--interactions at the triple phase reaction sites.