Thesis (Ph. D.)--School of Civil and Environmental Engineering, Georgia Institute of Technology, 2005. Directed by Ching-Hua Huang. / Wine, Paul, Committee Member ; Pavlostathis, Spyros, Committee Member ; Mulholland, James, Committee Member ; Yiacoumi, Sotira, Committee Member ; Huang, Ching-Hua, Committee Chair. Includes bibliographical references.

Thesis (Ph. D.)--Materials Science and Engineering, Georgia Institute of Technology, 2006. / Tannenbaum, Rina, Committee Chair ; Rosario Gerhardt, Committee Member ; Hamid Garmestani, Committee Member ; Karl Jacob, Committee Member Vita. Includes bibliographical references.

Orientadores: Claudia Herrera Tambeli, Luana Fisher / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-18T23:53:53Z (GMT). No. of bitstreams: 1 Brito_TaniaCristinaChicreAlcantarade_D.pdf: 972625 bytes, checksum: fad5a501fbd6f8e4ad43ce3d1b700242 (MD5) Previous issue date: 2011 / Resumo: Na tentativa de diminuir os efeitos colaterais de ação central associados ao uso dos analgésicos opióides, algumas estratégias têm sido desenvolvidas para que eles atuem especialmente nos receptores opióides periféricos. Nesse contexto, os receptores capa opióides são de grande interesse, uma vez que, em contraste com outros receptores opióides, sua ativação não está associada com efeitos colaterais periféricos significativos. Estudo recente, realizado em nosso laboratório demonstrou que a ativação de receptores capa opióides localizados na região da articulação temporomandibular de ratos reduz significativamente a nocicepção induzida pela administração do agente inflamatório formalina nessa mesma articulação. No entanto, ainda não havia sido investigado até então, se a ativação de receptores capa opióides localizados na região da articulação temporomandibular de ratos também diminuía a inflamação induzida pela formalina nessa mesma articulação. Nesse contexto, o objetivo deste estudo foi investigar se a ativação de receptores capa opióides localizados na região da articulação temporomandibular de ratos diminui o extravasamento plasmático e a migração de neutrófilos induzidos pela administração de formalina na articulação temporomandibular de ratos. A intensidade do extravasamento plasmático foi determinada pela concentração do corante Azul de Evans extravasado no tecido articular e a intensidade de migração de neutrófilos pela avaliação da atividade da enzima mieloperoxidase. Para avaliar as diferenças significativas entre os grupos de extravasamento plasmático e migração de neutrófilos foi usado o teste one-way ANOVA seguido do teste de Tukey e o nível de significância estatística foi p <0,05.Os dados estão expressos em valores como média ± S.E.M. A co- administração de formalina a 1,5% e U50,488 (agonista seletivo de receptor capa opióide) (50?g) reduziu significativamente o extravasamento plasmático (Média± EPM: 23,42 ?g/g ± 4,88) de forma dose dependente e reversível quando comparado com os demais grupos de 1,5?g (46,60 ?g/g; ± 5,40) e 30?g (37,60 ?g/g ±3,64). Quando o U50,488 foi administrado na articulação temporomandibular contralateral a que recebeu formalina 1,5%, ele não afetou o extravasamento plasmático. A co- administração de formalina a 1,5% e U50,488 (1,5?g) reduziu significativamente a migração de neutrófilo (1,10 ?g/mg ± 0,20) de forma dose dependente quando comparado com os demais grupos de 0,3?g (3,23?g/mg ± 0,56) e 0,75?g (2,4323 ?g/mg ± 0,42). Quando o U50,488 foi administrado na articulação temporomandibular contralateral a que recebeu formalina 1,5%, ele não afetou a migração de neutrófilos induzidos pela formalina. Este efeito antiinflamatório foi revertido pela administração prévia, na articulação temporomandibular ipsilateral, mas não contralateral, do antagonista seletivo do receptor capa opióide nor-BNI (cloridrato de nor-Binaltorfimina, 200?g). Este estudo demonstrou que a ativação local de receptores capa opióides na região da articulação temporomandibular reduz significativamente dois parâmetros importantes da inflamação, que são o extravasamento plasmático e a migração de neutrófilos, de uma forma dose-dependente e antagonista reversível. Esse efeito antiinflamatório, em conjunto com o potente efeito antinociceptivo previamente observado desse agonista capa opióide, sugere que drogas que atuem sobre os receptores capa opióides periféricos são promissoras para o tratamento da dor e da inflamação nas articulações temporomandibulares e, provavelmente, para o tratamento de outras condições de dor articular que possua componente inflamatório / Abstract: In an attempt to decrease central side effects associated with the use of opioids, some strategies have been developed by targeting peripheral opioid receptors. In this context, kappa opioid receptors are of major interest, since, in contrast to other opioid receptors, their activation is not associated with potent peripheral side effects. We have recently demonstrated that local activation of kappa opioid receptors significantly decreases formalin-induced temporomandibular joint nociception, however, whether it also decreases temporomandibular joint inflammation is not known. To address this issue, we evaluated if the selective kappa opioid receptor agonist, U50,488 (trans-(1S,2S)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] enzeneacetamide hydrochloride hydrate), administered into the temporomandibular joint decreases formalin-induced plasma extravasation and neutrophil migration. The intensity of plasma extravasation was determined by measuring the concentration of Evan's blue dye extravasated in the articular tissue and the intensity of leukocyte migration was determined by measuring Myeloperoxidase activity also in the articular tissue. Data were analyzed by ANOVA and Tukey post hoc test (p?0.05) and the results are expressed as mean ± EPM. The co-administration of 1.5% formalin with the selective kappa opiod receptor agonist U50,488 at 50 ?g significantly reduced the plasma extravasation (Mean±EPM: 23.42 ?g/g ± 4.88) compared to the other groups receiving 1.5% formalin plus U50,488 at 1.5?g (46.60 ?g/g ± 5,40) and at 30?g (37.60 ?g/g ± 3.64). When applied on the contralateral temporomandibular joint, U50,488 had no effect on formalin-induced plasma extravasation. The co-administration of 1.5% formalin with U50,488 at 1.5?g significantly reduced formalin-induced neutrophil migration (1.10 ?g/mg ±0.20) compared to the other groups receiving 1.5% formalin plus U50,488 at 0.3?g (3.23?g/mg ± 0.56) and at 0.75?g (2.43 ?g/mg ± 0.42). When applied on the contralateral temporomandibular joint, U50,488 had no effect on formalin-induced neutrophil migration. The anti-inflammatory effect of U50,488 was blocked by the ipsilateral, but not contralateral administration of the selective kapa opioid receptor antagonist nor-BNI (Nor-Binaltorphimine dihydrochloride). This study demonstrates that local activation of kappa opioid receptors decreases two important parameters of temporomandibular joint inflammation, that is, plasma extravasation and neutrophil migration, in a dose-dependent and antagonist-reversible manner. This anti-inflammatory effect taken together with the previously demonstrated potent antinociceptive effect of U50,488, suggest that drugs targeting peripheral kappa opioid receptors are promising for the treatment of inflammatory temporomandibular joint pain and probably, other articular pain conditions with an inflammatory basis / Doutorado / Fisiologia Oral / Doutor em Odontologia

Ph.D. / The research contained in this thesis was aimed at the applications of Lewis acids (metal triflate salts in particular) and Brønsted acids as catalysts for various organic synthesis reactions. The ultimate objective was to prepare combinations of the Lewis and Brønsted acids to form assisted acids. The assisted acids yield to the formation of highly acidic assisted acids which exhibit high activity as compared to the individual Lewis and Brønsted acids. A detailed literature study was undertaken, with emphasis on the applications of metal triflate salts as catalysts for various organic reactions and the applications of assisted acids. The study was motivated by the fact that metal triflate Lewis acids are thermally stable, non corrosive and water tolerant catalysts, hence can be used industrially to replace the corrosive, moisture sensitive acids as catalysts. However, metal triflates have not yet been recognised and utilised in the chemical industry. On the other hand, the active Brønsted acids such as triflic acid, H2SO4 etc. are corrosive, which restricts the type of construction material to hastelloy. However, the assisted acids composed of less corrosive Brønsted acids and metal triflate Lewis acid is desirable to address the corrosion and safety challenges. The metal triflate salts and Brønsted acids were evaluated as catalysts for etherification reactions of alcohols and olefins, Friedel-Crafts alkylation reactions phenolic substrates with isobutylene. The study showed that some dependence of the charge density to the activity, i.e. metal triflate salts such as Al(OTf)3, Zr(OTf)4 and Sc(OTf)3 with relatively high charge density were more effective in catalysing the reactions than those with relatively smaller charge density such as lanthanides, which were virtually active. The activity of Brønsted acids showed a clear dependence on the acid strength pKa, with H3PO4 giving the least activity. The assisted acids formed via a combination of metal triflate salts with mineral Brønsted acids showed a significant enhancement of the reaction rates as compared to the individual acids. This set of new combined acids was proven to be excellent catalysts for the etherification reactions, Friedel-Crafts alkylation reactions and also for the synthesis of biologically active compounds called chromans. The assisted acids as well as Al(OTf)3, and Zr(OTf)4 could be recycled at least four times without significant loss of activity. The study also showed that assisted acids could be recycled for both etherification and Friedel-Crafts reactions.

The nucleotide 2'-deoxythymidine 5'-monophosphate (thymidylate, dTMP) is phosphorylated twice to become a substrate for DNA polymerases, which copy a cell’s genetic information in advance of cell division. The main route to dTMP is mediated by the enzyme thymidylate synthase (TSase) and goes through 2'-deoxyuridine 5'-monophosphate (dUMP); dUMP’s heterocyclic aromatic pyrimidine ring loses a proton from its C5 position and gains a methylene and a hydride from the other reactant, methylene tetrahydrofolate (MTHF). In general, intricate knowledge of an enzyme’s mechanism can yield insight that leads to the development of precision-targeted inhibitors tailored exactly to thymidylate synthase. In fact, even more careful targeting could be achievable: Although E. coli TSase has served as a model system, investigators have increasingly been directing their lines of inquiry toward human TSase. A general enzymatic catalytic cascade is complex, comprising substrate binding, the chemical steps and product release; typically, the product release step is rate-limiting. TSase, however, is partially rate-limited by the chemistry portion of the process. The enzymatic mechanism has been considered for decades, yet recently has undergone a reassessment. After substrate binding – for which there is strong evidence for preference to dUMP as the first ligand in the wild-type E. coli enzyme – the important events are methylene transfer from MTHF to dUMP, proton abstraction and hydride transfer. The last of these – hydride transfer – is irreversible and rate-limiting (to a large degree without Mg2+, and to a small but noticeable degree with Mg2+). The studies described here are aimed at three therapeutically relevant questions: (a) determining the extent of negative charge accumulation at the O4 position of the hydride transfer acceptor; (b) expanding knowledge of the differential properties of E. coli and human TSase; and (c) gaining insight into the molecular origin of the drug resistance seen in a clinically relevant human TSase mutant. The properties touched on in this work include steady-state kinetics; inhibition constants toward 5-fluoro dUMP, substrate binding sequence and the temperature dependency of intrinsic hydride transfer kinetic isotope effects (KIEs). Intrinsic KIEs are a specialized measurement that permits the investigator to examine a particular hydrogen transfer step in isolation; it is achieved by labeling the bond to hydrogen broken in the reaction with protium (1H, also written as H), deuterium (2H, also written as D) or tritium (3H, also written as T). The latter is radioactive. The reaction is conducted with a mixture of two hydrogen isotopes at a time, and the extent to which the heavier isotope is disfavored against reaction is assessed; this covers multiple steps. Heavier isotopes directly participating in a chemical step react slower both because of zero-point vibrational energies if a semi-classical view is taken and because of the mass-dependence of tunneling probabilities if a quantum-mechanical view is taken. Each of the two-way isotopic comparisons mentioned above furnishes an observed KIE for that competition between two isotopes. Mathematical combination of two isotopic comparisons cancels out the effect of isotopically insensitive steps and provides rich insight into the hydride transfer alone. The ultimate result is the ratio of rate constants for the isotopologues; this ratio’s magnitude and variation with temperature report on the compactness of the active site and its resistance to thermal fluctuation, respectively. Our results reveal a possible role for E. coli asparagine 177 (N177) in the hydride transfer transition state (TS) stabilization, as revealed by its disruption in the aspartate mutant, N177D. This disruption was found to be alleviated to a high extent when the substrate was changed to dCMP, consistent with the N177 stabilizing partial negative charge at the TS for hydride transfer. This has drug design implications. Our work on human TSase underscores slightly weaker substrate binding preference, insensitivity to Mg2+ and mild alteration of hydride transfer TS when compared with E. coli TSase. Finally, analysis of the Y33H mutant of human TSase – the affected residue being remote from the active site – indicated the drug resistance was because of a higher inhibition constant for 5F-dUMP and that the hydride transfer step is disrupted, with a wider variation among donor-acceptor distances (between the two carbons involved in the hydride transfer at the TS for that step). Other researchers’ crystallographic evidence reveals greater positional uncertainty for a set of active-site side chains in the E. coli equivalent mutant. In totality, the data available implicate enzyme motions as relevant to drug binding and to catalysis for human TSase. In summary, the research described herein enriches the understanding of several aspects of the behavior of multiple TSase variants – the overall performance as seen via steady-state kinetics; the pattern of substrate binding as seen with observed KIEs for the proton abstraction step; and the efficiency of active site preparation for hydride transfer as evidenced in the temperature dependency of intrinsic hydride transfer KIEs.

No description available.

Theoretical investigation of microporous materials for adsorption and catalysis Microporous materials are defined by a presence of pores with diameter smaller than 2 nm. They comprise a large variety of materials from amorphous materials to very well defined crystalline materials like zeolites or metal organic frameworks. Microporous materials are industrially very important group of materials used for adsorption, gas capture, molecular sieving, or heterogeneous catalysis. Zeolites are by far the most important group of microporous materials due to their use as catalysts for the petroleum cracking. One of the main limitations of the zeolite use in catalysis is their limited pore size. This obstacle can be solved by use of hierarchical zeolites with a secondary mesopore network which allows overcoming the diffusion problems. The aims of this study can be divided into two parts. In the first part, the structures of two-dimensional and hierarchical zeolites were investigated theoretically to identify the structure of new materials and to obtain reliable models to study the hierarchical zeolites. In the second part, the catalytic properties of several microporous materials were modelled to explain their experimental activity. The results of this thesis were used to identify the structure of a large...

Title: Study of C-C coupling of dienes catalyzed by ruthenium (II) complexes. Author: Bc. Eva Hanikýřová Department: Department of Organic Chemistry Supervisor: Mgr. Jana Roithová, Ph.D. Abstract Transition metal catalyzed cycloadditions have contributed extensively to organic synthesis. The use of ruthenium complexes in those reactions gain importance due to their demonstrated ability in the catalytic carbon-carbon bond formations via ruthenacycle intermediates. In our studies, we have concentrated on the interaction between ruthenium (II) and alkenes using mass spectrometry with electrospray ionization. This technique allows to investigate ruthenium complexes in the ionized states, and allows to investigate these structures by using MS/MS analyse. Our experimental research was complemented by quantum chemical calculations using Density functional theory. The research leads to a more detailed understanding to Ruthenium complexes with unsaturated hydrocarbons reaction mechanism. Key words Gas-phase chemistry, Reaction mechanisms, Electrospray Ionization, Catalyst, [CpRu(CH3CN)3]PF6, Mass Spectrometry

The power transformer is a critical equipment in which the protection process is essential for modern societies where continuous electric power supplies are required. Copper corrosion problems due to the formation of sulfur deposits on the copper windings of mineral oil-filled power transformers are considered a major issue that can lead to sudden failures, and in some cases, to costly fire and explosion accidents in the power plants. These kinds of problems are still being reported regardless of available condition monitoring (CM) parameters applied in power transformers' maintenance strategy. The currently applied CM parameters are based on three different types of technologies. The first is oil analysis focuses more on measurable variables such as measuring the concentration of the corrosive sulfur compounds in the insulating oil, evaluating the oil's capability to form sulfur deposits, and measuring an increase in the concentration of specific gases. The second is on-site electrical testing focuses on the variation of the transformer's electrical properties due to the sulfur deposits. The measurable variables used in the electrical testing are Frequency Domain Spectroscopy test and Polarization/Depolarization Current test. The last is online sensor technology using Corrosive Sulfur Sensor, where the sensor's outcome data provide information about the oil's capability to form sulfur deposits. The research problem addressed is how to establish more effective CM parameters for early detection of copper corrosion problems.  The research problem is divided into three concretized research problems: What are the strengths and weaknesses of the currently applied condition monitoring parameters? Which measurable variables could be utilized to improve the currently applied condition monitoring parameters to be more effective for early detection of copper corrosion problems? And how to establish a procedure for the condition monitoring for detecting copper corrosion? Two research methodologies were applied to answer these questions, literature review and experimental work. The literature review showed significant gaps in the currently applied CM parameters for early detection of copper corrosion problems due to incomplete data of the corrosion reaction mechanism. Therefore, qualitative and quantitative investigations in the experimental work were carried out. The most important result was finding new relevant measurable variables, i.e. hydrogen sulfide gas and toluene compound, which are by-products of corrosion reaction. These measurable variables are utilized to establish more effective CM parameters for early detection of copper corrosion problems. The main conclusion of this thesis is the importance of detection corrosion problems in the initial stage by implementing more effective CM parameters to prevent catastrophic and costly failures, reduce the negative impacts on human life and the environment, and save the economic losses. Another conclusion is the importance of regularly following the measurable variables' uptrend during transformer useful life to avoid incorrect evaluation of corrosion conditions.

No description available.