Orientador: Luiz Gonzaga Gandini Junior / Banca: Ary dos Santos Pinto / Banca: Lídia Parsekian Martins / Banca: Hélio Terada / Banca: Ricardo Sampaio de Souza / Resumo: O propósito desse estudo foi avaliar os efeitos transversais nos maxilares e o crescimento mandibular ântero-posterior após terapia com aparelho ortopédico funcional. A amostra foi composta por 25 pacientes (15 do gênero masculino e 10 do gênero feminino) com má oclusão de Classe II e idade variando entre 6.9 e 11.2 anos. Os pacientes foram aleatoriamente divididos em dois grupos, grupo controle (n=11) e grupo experimental (n=14) e acompanhados longitudinalmente por 12 meses. O tratamento foi exclusivamente executado com o aparelho bionator de Balters por um período de 12 meses. O método de sobreposição, com auxílio de implantes metálicos, foi realizado na avaliação das alterações esqueléticas transversais dos maxilares, crescimento condilar e remodelação óssea da mandíbula. Os resultados mostraram que os pacientes sem tratamento exibiram um aumento significante, em largura, entre os implantes maxilares posteriores, mas a diferença entre os implantes anteriores e mandibulares não foi estatisticamente significante. A distância entre os implantes posteriores, no sentido transversal, aumentaram significantemente para os dois grupos, com o grupo bionator mostrando um aumento significativo maior do que o grupo controle. O grupo bionator também mostrou uma maior expansão entre os implantes localizado na mandíbula, porém essa diferença não foi estatisticamente significante. Com relação ao crescimento condilar, os resultados mostraram um redirecionamento do crescimento (mais posterior), e semelhante quantidade de crescimento para os dois grupos. O tratamento com o aparelho bionator produziu um crescimento e remodelação óssea maior do que o esperado nas regiões condilar e goniana da mandíbula. Sobreposição na base do crânio mostrou um deslocamento anterior da mandíbula e uma pequena ou quase ausente rotação anterior... (Resumo completo, clicar acesso eletrônico abaixo). / Abstract: The purpose of this study was to describe transverse skeletal base adaptations and mandibular growth associated with bionator therapy. The sample included 25 patients (15 males and 10 females) between 6.9 and 11.2 years of age with Class II division 1 malocclusion. The patients were randomly allocated to either a control (n=11) or treatment (n=14) group. Treatment consisted of a bionator only, and the patients were following longitudinally for approximately 12 months. Using metallic implants for superimposition, transverse skeletal base adaptations, condylar growth and mandibular remodeling changes were evaluated. The results showed that untreated Class II controls exhibit significant increases between posterior maxillary implants, but no significant changes between the anterior maxillary or mandibular implants. While posterior maxillary implants increased significantly in both groups, the treated group showed significantly greater width increases than the control group. The treated group also showed greater increases between mandibular implants, but the differences were not statistically significant. Condylar growth in perspective, the results showed significant changes in the direction (more posterior) but not in the amount of overall amount of condylar growth. The bionator appliance produced greater than expected posterior drift of landmarks in the condylar and gonial regions. Cranial base superimposition showed greater than expected anterior mandibular displacement, but little or no true mandibular forward rotation with bionator therapy. In conclusion, the bionator appliance alone produces transverse skeletal adaptations, condylar growth redirection and remodeling changes associated with mandibular rotation and displacement. / Doutor

A study was carried out to improve the flotation selectivity between galena and sphalerite during the flotation of a Cu-Pb-Zn sulphide composite ore from the Rosh Pinah Mine (Namibia). Xanthate collectors were found to be unselective for the flotation of the Rosh Pinah composite sample. It was observed that the recovery of sphalerite increased with both the recovery of galena and the concentrate mass pull. In addition, the recovery of sphalerite increased after activation with Cu(II) ions while that of galena decreased when the composite was dry ground in a mild steel mill with mild steel grinding media. However, the recovery of galena was not affected after wet milling in a stainless steel mill. The recovery of Cu(II)-activated sphalerite was independent of the milling environment (wet or dry) and grinding media. The activation of sphalerite by cuprous cyanide complexes, which are present in the recycled water, was clearly shown in this study. Both batch flotation tests and XPS analysis have confirmed that sphalerite was activated by copper(I) from the cuprous cyanide complexes. The recovery of copper(I)-activated sphalerite increased further when the composite was dry milled as compared to wet milling. Batch flotation tests have shown that the use of cyanide alone is not efficient for the depression of sphalerite due to the mineralogical texture of the Rosh Pinah ore. A large quantity of galena locked and/or attached to sphalerite was observed in the lead concentrate. Their prevalence increased with increasing particle size. The use of both cyanide and zinc sulphate improved the depression of sphalerite much better than cyanide alone. A flowsheet has been proposed to improve selectivity between galena and sphalerite in the lead flotation circuit. It includes the regrinding of the lead rougher concentrate prior to the cleaning stage due to poor liberation between galena and sphalerite. / Thesis (PhD (Metallurgical Engineering))--University of Pretoria, 2006. / Materials Science and Metallurgical Engineering / unrestricted

In this thesis, the reactivity and synthesis of methylalumoxane (MAO) via electrospray ionization mass spectrometry (ESI-MS) was investigated. The olefin polymerization catalyst [Cp2Zr(μ-Me)2AlMe2]+ [B(C6F5)4]− was also used to evaluate the efficacy of a nitrogen generator as a source for desolvation gas for ESI-MS analysis. The same catalyst was then used to study catalyst deactivation after 1-hexene addition. MAO ionizes very selectively in the presence of octamethyltrisiloxane (OMTS) to generate [Me2Al·OMTS]+ [(MeAlO)16(Me3Al)6Me]−. The advantage of this transformation was used to examine the reactivity and synthesis of MAO. The reactivity of this ion pair with other trialkyl aluminum (R3Al) components was studied both offline and in real-time. The exchanges are fast and reversible, and the methyl groups on the cation are also observed to exchange with the added R3Al species. MAO is also famously intractable to structural elucidation, consisting as it does of a complex mixture of oligomers generated from hydrolysis of pyrophoric trimethylaluminum (TMA). Synthesis of MAO was probed in real-time by ESI-MS, and the principal activated product of the benchtop synthesis was found to be the same as that observed in industrial samples, namely [(MeAlO)16(Me3Al)6Me]–. Computationally, a new sheet structure for this ion was proposed. The increasing competitiveness of nitrogen generators, which provide gas purity levels that vary inversely with flow rate, prompted an investigation of the effect of gas-phase oxygen on the speciation of ions by ESI-MS. The most reactive species studied, the reduced titanium complex [Cp2Ti(NCMe)2]+[ZnCl3]− and the olefin polymerization pre-catalyst [Cp2Zr(μ-Me)2AlMe2]+[B(C6F5)4]−, only exhibited detectable oxidation when they were rendered coordinatively unsaturated through in-source fragmentation. The catalyst [Cp2Zr(μ-Me)2AlMe2]+[B(C6F5)4]− was further studied by ESI-MS to understand better the complexities of catalyst deactivation in the polymerization of 1-hexene. I also contributed to other projects, namely the interaction of neutral donors with MAO, saturation problems in ESI-MS, and ligand substitution reaction in ruthenium complexes, and my work on all these projects are summarized in this thesis. / Graduate

In this work the influence of alkaline activator on immobilization of lead and copper in alkali-activated blast furnace slag was investigated. A total of five activators were used; sodium water glass, potassium water glass, sodium hydroxide, potassium hydroxide and sodium carbonate. The leaching test according to ČSN EN 12457-4 was used to evaluate the level of immobilization of heavy metals, the leached solutions were analyzed by ICP-OES. For a better understanding of immobilization, the selected samples were characterized by analytical methods (FTIR, XRD, SEM, XPS). It was found that the degree of immobilization Pb2+ and Cu2+ in AAS was very high, regardless of the type of alkaline activator used.

Diploma thesis studies historical bonding agents on the base of geopolymers. The aim of the thesis is to find a proper material composition, especially made of natural clay materials (kaolinite, bentinite) and their modifications (metakaoline). These bonding agents have to have a suitable type of an activator that guarantees good bonding properties. Therefore testing of various kinds of alkaline activating ingredients on the same mineral composition was done. Except of usual hydroxides and a water glass, ancient natrons (mixtures of alkaline carbonate with addition of appropriate chlorides) and a lime mash were used as the activators. From the above mentioned mixtures, series of samples (columns 20 x 20 x 100 mm) stored at the laboratory temperature were prepared. In the prepared mashes, their workableness and moulding were investigated. In the developed samples, their surface appearance was observed together with a number of efflorescence and its types. An indivisible part of the research was formed by determination of mechanical properties of the experimental columns such as a compressive strength and a tensile strength in bending. Furthermore, phase composition of the samples and its changes with a temperature increase were investigated. For these tests, XRD and TG – DTA methods were used. A multi-seat isoperbolic calorimeter was used to study hydratation that was also the important part of the general evaluation of designed mixtures.

Chapter II Abstract Human positive cofactor 4 (PC4) is a transcriptional coactivator with a highly conserved single-strand DNA (ssDNA) binding domain of unknown function. We identified PC4 as a suppressor of the oxidative mutator phenotype of the Escherichia coli fpg mutY mutant and demonstrate that this suppression requires its ssDNA binding activity. Saccharomyces cerevisiae mutants lacking their PC4 ortholog Sub1 are sensitive to hydrogen peroxide and exhibit spontaneous and peroxide-induced hypermutability. PC4 expression suppresses the peroxide sensitivity of the yeast sub1Δ mutant, suggesting that the human protein has a similar function. A role for yeast and human proteins in DNA repair is suggested by the demonstration that Sub1 acts in a peroxide resistance pathway involving Rad2 and by the physical interaction of PC4 with the human Rad2 homolog XPG. We show that XPG recruits PC4 to a bubble-containing DNA substrate with a resulting displacement of XPG and formation of a PC4-DNA complex. We discuss the possible requirement for PC4 in either global or transcription-coupled repair of oxidative DNA damage to mediate the release of XPG bound to its substrate. Chapter III Abstract Previously I established that (1) PC4 significantly suppresses oxidative mutagenesis via its single-strand DNA binding activity, (2) a partial suppression of H2O2-induced lethality was observed in a sub1Δ rad2Δ yeast double mutant compared to the sub1Δ mutant, and (3) PC4 interacts with XPG physically and functionally. These results led me to believe that suppression of oxidative mutagenesis and lethality by PC4 is partially due to its function in an XPG/Rad2-dependent pathway and through additional unidentified mechanism(s). In this chapter, I present studies aimed at investigating different DNA repair pathways in which PC4/Sub1 might participate. I address the possible roles of PC4/Sub1 in transcription-coupled repair (TCR) in terms of its binding specificity to oxidative DNA lesions and its ability to allow efficient resumption of transcription after oxidative DNA damaging treatment. To ask if PC4/Sub1 interacts with other DNA repair proteins to protect cells from oxidative DNA damage, I analyzed spontaneous mutation rates among a series of isogenic, haploid yeast mutant strains deficient of SUB1, base excision repair (BER) and/or nucleotide excision repair (NER) functions. I further analyzed genetic interactions between SUB1 and genes critical to various DNA damage avoidance/tolerance mechanisms, such as mismatch repair (MMR), homologous recombination (HR) and translesion synthesis (TLS).

Carbonic anhydrases (CAs, EC 4.2.1.1) are a class of metalloenzymes that catalyze the hydration of CO2 under physiologic conditions and are involved in many physiological and pathological processes. Modulation of CA activity, particularly CA inhibition is exploited pharmacologically for the treatment of many diseases such as cancer, glaucoma, edemas, mountain sickness. CA activation has been less frequently investigated till recently. Genetic deficiencies of several CA isozymes are reported in the literature and reflect the important role of carbonic anhydrases in human physiology and homeostasis. Activation of CA isozymes in brain have been correlated recently with spatial learning and memory. Based on these premises, activators of CA isozymes have the potential to alleviate mild dementias and to act as potential nootropic agents. In chapter 3, continuing our long-term interests towards the development of potent and selective CAAs, we carried out X-ray crystallographic studies with a small series of pyridinium histamine derivatives, previously developed as CAAs by our group. This study revealed important insights into the binding of this class of activators into the active site of CA II isozyme. A potent pyridinium histamine CAA 25i was successfully crystallized with CA II isozyme and was found to bind into the hydrophobic region of the active site, with two binding conformations being observed. This is one of the very few X-ray crystal structures of a CAA available. Based on the findings of this X-ray crystallographic study and building on our previously developed ethylene bis-imidazole CAAs, we advanced a novel series of lipophilic bis-imidazoles. Enzymatic assays carried out on purified human CA isozymes revealed several low nanomolar potent activators against various brain-relevant CA isozymes. Bis-imidazole 30e was found to be a nanomolar potent activator for CA IV, CA VA and CA IX. Due to their conjugated structure, these CAAs were also fluorescent and therefore were fully characterized in terms of photophysical properties, with several representatives proving to display very good fluorophores. The very good activation profile against several different CA isozymes, along with excellent fluorescence properties recommend these compounds as great molecular tools for elucidation of role of CA isozymes in brain physiology, as well as towards improvement of memory and learning. Focusing on inhibition of CA isozymes, it must be stressed that over the last decade a clear connection had been established between the expression of CA IX and CA XII and cancer. Since cancer is the second most common cause of death in the world, we explored the possibility to kill cancer cells via inhibition of different CA isozymes present in cancer cells. The membrane bound carbonic anhydrase IX (CA IX) isozyme represents a particularly interesting anticancer target as it is significantly overexpressed in many solid tumors as compared to normal tissues. In malign tissues this CA isozyme was found to play important role in pH homeostasis and promotes tumor cell survival, progression and metastasis. Thus, CA IX represents a potential biomarker and an appealing therapeutic target for the detection and treatment of cancer. CA IX can be targeted either through the development of small or large molecular weight, potent, and selective inhibitors or through the development of CA IX targeted drug delivery systems for selective delivery of potent chemotherapeutic agents. Building on these premises, in this dissertation, we also revealed our continuing efforts towards the development of potent and selective CA IX inhibitors along with their translation into the development of CA IX targeted drug delivery systems. In chapter 4, we designed a series of small molecular weight (MW) ureido 1,3,4-thiadiazole sulfonamide derivatives employing the “tail approach”, through the decoration of established sulfonamide CA inhibitor warheads with different tail moieties via ureido linker. The generated CAIs were tested against tumor associated CA IX and CA XII isozymes and off-target cytosolic isozymes CA I and CA II, and were revealed to be moderate to highly selective and nanomolar, even sub-nanomolar, potent CA IX inhibitors. Several potent pan-inhibitors were also identified in this section. We assessed these CAIs for their in vitro cell killing ability using MDA-MB 231 breast cancer cell line expressing CA IX and CA XII. The most efficient CAI proved to be ureido-1,3,4-thiadiazole-2-sulfonamide 69, which showed subnanomolar potency against purified human CA IX and CA XII isozymes, with good selectivity against CA I and CA II, and consistent, statistically significant cancer cell killing. In Chapter 5, continuing our efforts towards the development of potent and selective CA IX inhibitors, we designed, synthesized, characterized and evaluated a new series of PEGylated 1,3,4-thiadiazole-2-sulfonamide CAIs, bearing different PEG backbone length. We increased the PEG size from 1K to 20K, in order to better understand the impact of the PEG linker length on the in vitro cell killing ability against CA IX expressing cancer cell lines and also against a CA IX negative cell line. In vitro cell viability assays revealed the optimum PEG linker length for this type of bifunctional bis-sulfonamide CAIs in killing the tumor cells. The most efficient PEGylated CAI was found to bis-sulfonamide DTP1K 91, which showed consistent and significant cancer cell killing at concentrations of 10−100 μM across different CA IX and CA XII expressing cancer cell lines. DTP1K 91 did not affect the cell viability of CA IX negative NCI-H23 tumor cells, thus revealing a CA IX mediated cell killing for these inhibitors. In chapter 6, we decided to further explore the possibility of using CA IX as a targeting epitome for the development of a gold nanoparticle-based drug delivery system. We translated the oligoEG- and PEGylated CAI conjugates into efficient targeting ligands for gold nanoparticle decoration along with chemotherapeutic agent doxorubicin (Dox), in a novel multi-ligand gold nanoplatform designed to selectively release the drug intracellularly, in order to enhance the selective tumor drug uptake and tumor killing. We were successful in developing compatible CAI- and Dox- ligands for efficient dual functionalization of gold nanoparticles. Our optimized, CA IX targeted gold nanoplatform was found to be very efficient towards killing HT-29 tumor cells especially under hypoxic conditions, reducing the hypoxia-induced chemoresistance, thus confirmed the potentiating role of CA IX as a targeting epitome. / Pharmaceutical Sciences

No / Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (Tm). Surfactants also removed the lipid pre-transition but reduced Tm and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower Tm. The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced Tm and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The Tm and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2 mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

The work described in this thesis was aimed at understanding the reactions taking place on heating Y2O3:Eu3+ phosphor precursors in the nano particle size regime. Herein combustion syntheses to prepare nanometer sized crystallites of cubic Y2O3:Eu3+ using precursors containing sacrificial long chain alkylammonium cations (the fuel) are reported. Using this method it proved possible to produce cubic Y2O3:Eu3+ crystallites in the 20-70nm size range. The presence of CO2 bands in the infra red spectra of the surface of the cubic Y2O3:Eu3+ crystallites are also reported. These bands are identical in position to those found in [(Y, Eu)OHCO3.H2O], and are explained as arising from the spontaneous reaction of the surface of the nanometer sized particles of cubic Y2O3:Eu3+ with atmospheric CO2 and water vapour. This indicates that nanometer sized particles of cubic Y2O3:Eu3+ are thermodynamically unstable in the atmosphere and must be protected against such back reactions. This could be done with surface coatings. Precursors of the products were prepared from methanolic and ethanolic solutions and then these were fired at temperatures of 650 and 900°C. Products (samples) prepared at a temperature of 900°C were observed to be all white powders in colour. Under 254nm uv excitation the samples prepared at 650°C displayed a weak red luminescence which was in contrast to the strong red luminescence from the samples prepared at 900°C that is characteristic of the Eu3+ ion in cubic Y2O3. The strongest red luminescence comes from 1:3 material sample ratios prepared at 900°C. The understanding of the chemistry behind the reactions and the characterisation and properties of the products formed are the major aims of the work reported here.