Recent design trends in steam turbines strive for high aerodynamic loading and high aspect ratio to meet the demand of higher efficiency. These design trends together with the low structural frequency in last stage steam turbines increase the susceptibility of the turbine blades to flutter. Flutter is the self-excited and self-sustained aeroelastic instability phenomenon, which can result in rapid growth of blade vibration amplitude and eventually blade failure in a short period of time unless adequately damped. To prevent the occurrences of flutter before the operation of new steam turbines, a compromise between aeroelastic stability and stage efficiency has to be made in the steam turbine design process. Due to the high uncertainty in present flutter prediction methods, engineers use large safety margins in predicting flutter which can rule out designs with higher efficiency. The ability to predict flutter more accurately will allow engineers to push the design envelope with greater confidence and possibly create more efficient steam turbines. The present work aims to investigate the influence of tip clearance flow on the prediction of steam turbine flutter characteristics. Tip clearance flow effect is one of the critical factors in flutter analysis for the majority of aerodynamic work is done near the blade tip. Analysis of the impact of tip clearance flow on steam turbine flutter characteristics is therefore needed to formulate a more accurate aeroelastic stability prediction method in the design phase.Besides the tip leakage vortex, the induced vortices in the tip clearance flow can also influence blade flutter characteristics. However, the spatial distribution of the induced vortices cannot be resolved by URANS method for the limitation of turbulence models. The Detached-Eddy Simulation (DES) calculation is thus applied on a realistic-scale last stage steam turbine model to analyze the structure of induced vortices in the tip region. The influence of the tip leakage vortex and the induced vortices on flutter prediction are analyzed separately. The KTH Steam Turbine Flutter Test Case is used in the flutter analysis as a typical realistic-scale last stage steam turbine model. The energy method based on 3D unsteady CFD calculation is applied in the flutter analysis. Two CFD solvers, an in-house code LUFT and a commercial software ANSYS CFX, are used in the flutter analysis as verification of each other. The influence of tip leakage vortex on the steam turbine flutter prediction is analyzed by comparing the aeroelastic stability of two models: one with the tip gap and the other without the tip gap. Comparison between the flutter characteristics predicted by URANS and DES approaches is analyzed to investigate the influence of the induced vortices on blade flutter characteristics. The multiple induced vortices and their relative rotation around the tip leakage vortex in the KTH Steam Turbine Flutter Test Case are resolved by DES but not by URANS simulations. Both tip leakage vortex and induced vortices have an influence on blade loading on the rear half of the suction side near the blade tip. The flutter analysis results suggest that the tip clearance flow has a significant influence on blade aerodynamic damping at the least stable interblade phase angle (IBPA), while its influence on the overall shape of the damping curve is minor. At the least stable IBPA, the tip leakage vortex shows a stabilization effect on rotor aeroelastic stabilities while the induced vortices show a destabilization effect on it. Meanwhile, a non-linear unsteady flow behavior is observed due to the streamwise motion of induced vortices during blade oscillation, which phenomenon is only resolved in DES results.

Optimization of reproductive efficiency of both beef and dairy herds is critical for sustainability and profitability. Two separate experiments were performed to test the reproductive outcomes following early weaning of beef heifers and intrafollicular insemination in dairy cows. Early weaning is a proven way to induce precocious puberty in heifers. Heifers will experience more estrous cycles before breeding, which is associated with increased fertility. In this experiment, heifers were either subjected to early weaning and a high concentrate diet (EW; 106.5±3.4 days of age) or normal weaning (NW; 231.7±3.33 days of age) treatments. Despite no effect (P>0.15) of weaning treatment on age at puberty, EW heifers tended to have higher pregnancy rates than NW heifers. A progesterone clearance analysis revealed that EW heifers also have greater ability to metabolize progesterone. This altered progesterone metabolism could be a direct result of changes in metabolism caused by feeding a high concentrate diet after early weaning. Pregnancy rates in cattle are often lower than desired. New reproductive advances are constantly developed to improve reproductive function. A recently described possible technique is intrafollicular insemination (IFI). The objective of the second experiment was to investigate whether IFI can cause fertilization. Abattoir ovaries with dominant follicles injected with semen and incubated overnight displayed sperm in close association with granulosa cells. When synchronized cows were subjected to IFI, no pregnancies resulted. While other studies have demonstrated success with IFI, it is still unknown if fertilization is possible within the follicle of the ovary. / Master of Science

Delayed uterine clearance (DUC) is a significant problem contributing to subfertility and infertility in the mare, characterized by an accumulation of fluid and inflammatory debris in the uterine lumen following breeding events, venereal disease or an estral cycle. This syndrome is typically seen in older, multiparous mares and mares with poor reproductive tract conformation. The etiopathogenesis of DUC has not been fully elucidated but suggested causes include poor genital conformation, a cranioventrally tilted uterus, defective myometrial contractions, decreased intrauterine immune activity, inappropriate lymphatic drainage or mucus overproduction. The objective of this research was to evaluate gene expression of selected genes in endometrial tissue samples taken from three categories of mares (young fertile [YF], older clinically normal [ON] and older susceptible [OS]). The genes assayed in this research were oxytocin receptor, PGF2á receptor and progesterone receptor. The expression of each of these genes was normalized using the expression of two housekeeping genes, beta actin and ribosomal 18S RNA. Quantitative real-time polymerase chain reaction (QPCR) was used to evaluate gene expression of the selected genes. Results indicated that there was no statistically significant difference in the expression of any of the three experimental genes among any of the three categories of mares. From this research, the direction of further research regarding the pathogenesis of DUC can be made: myometrial tissues can be assayed for similar genes, the expression of other genes regulating myometrial contraction can be assayed or the expression of uterorelaxants can be studied. / Master of Science

No / PURPOSE. Epidemiologic studies have indicated that elderly people who wear multifocal spectacles have an increased risk of tripping, particularly on stairs. Yet no studies have experimentally examined how wearing multifocal spectacles affects stair and step negotiation. The purpose of this study was to determine the effects of wearing multifocal compared with single-distance vision spectacles on minimum toe clearance and risk of tripping during step negotiation in the elderly. METHODS. Nineteen healthy subjects (mean age, 71.4 years) performed a single step up to a new level (heights, 7.5, 15, and 22 cm) while wearing multifocal (bifocals and progressive addition lenses) or single-distance vision spectacles. Minimum horizontal and vertical toe clearance were assessed by analyzing data collected with a five-camera, three-dimensional motion-analysis system. RESULTS. There was no difference in mean minimum toe clearance in subjects when wearing multifocal compared with single-distance vision spectacles. However, there was greater within-subject variability in vertical toe clearance when wearing multifocal spectacles (variance ratio, 1.53; P = 0.0004). Subjects were also significantly more likely to trip when wearing multifocal compared with single-vision spectacles (one-sided Fisher's exact test P = 0.025). CONCLUSIONS. Because of increased within-subject variability in vertical toe clearance when wearing multifocal spectacles, elderly individuals may be at greater risk of falling when negotiating steps and stairs if they do not also consistently increase margins of safety (mean vertical toe clearance). This suggests that some elderly who are at high risk of falling may benefit from wearing single-distance vision rather than multifocal spectacles when walking.

No / The importance of peripheral visual cues in the control of minimum-foot-clearance during overground locomotion on a clear path was investigated. Eleven subjects walked at their natural speed whilst wearing goggles providing four different visual conditions: upper occlusion, lower occlusion, circumferential–peripheral occlusion and full vision. Results showed that under circumferential– peripheral occlusion, subjects were more cautious and increased minimum-foot-clearance and decreased walking speed and step length. The minimum-foot-clearance increase can be interpreted as a motor control strategy aiming to safely clear the ground when online visual exproprioceptive cues from the body are not available. The lack of minimum-foot-clearance increase in lower occlusion suggests that the view of a clear pathway from beyond two steps combined with visual exproprioception and optic flow in the upper field were adequate to guide gait. A suggested accompanying safety strategy of reducing the amount of variability of minimum-foot-clearance under circumferential–peripheral occlusion conditions was not found, likely due to the lack of online visual exproprioceptive cues provided by the peripheral visual field for fine-tuning foot trajectory.

As infecções são a causa mais freqüente de morbidade e mortalidade observadas tanto aguda como tardiamente nos pacientes receptores de transplante pulmonar, o que pode estar diretamente relacionado a uma deficiência no transporte mucociliar do sistema respiratório. Nosso objetivo foi avaliar a influência de dois fatores envolvidos com o transplante pulmonar sobre o transporte mucociliar de ratos: a secção e anastomose brônquica e a imunossupressão pela ciclosporina A. Setenta e dois ratos foram distribuídos aleatoriamente em cinco grupos de acordo com: i) procedimento operatório e ii) terapia a que seriam submetidos. Os resultados mostram que houve uma diminuição significativa da Freqüência de Batimento Ciliar in situ, da Transportabilidade do Muco in vitro e da Velocidade de Transporte Mucociliar in situ medidos a partir do brônquio principal esquerdo dos ratos tratados com ciclosporina A (p<0,001). A Freqüência de Batimento Ciliar in situ dos brônquios operados mostrou-se diminuída também no grupo tratado com solução salina e sacrificado no 30º dia após a operação (p=0,001). Já a Velocidade de Transporte Mucociliar in situ mostrou uma diminuição significativa em todos os grupos submetidos à secção brônquica (p<0,001). Houve um efeito sinérgico entre a terapia com ciclosporina A e a secção brônquica, causando um prejuízo ao transporte mucociliar ainda maior do que quando analisados isoladamente. Concluímos que a Velocidade de Transporte Mucociliar in situ foi agudamente prejudicada após a secção brônquica e terapia imunossupressora pela ciclosporina A, havendo diminuição da freqüência de batimento dos cílios e alteração das propriedades viscoelásticas do muco respiratório. / Infections are the most common cause of early and late morbidity and mortality in lung transplant recipient, and can be directly related to impaired mucociliary transport. Our aim was to assess the influence of bronchial section and imunossupression on mucociliary transport in rats. Seventy two rats were randomly distributed in five groups according to i) surgical procedure and ii) drug therapy. There was a significant impairment on Ciliary Beating Frequency in situ, Mucus Transportability Rate in vitro and Mucociliary Transport Speed in situ from operated bronchus of cyclosporine A-treated rats (p<0.001). Ciliary Beating Frequency from operated bronchus was also impaired in saline-treated rats that were killed on 30th postoperative day (p=0.001). Mucociliary Transport Speed was impaired in all bronchi underwent to section (p<0.001). We conclude that bronchial section and cyclosporine therapy impaired all factors analyzed. Also there was a synergic effect between cyclosporine therapy and bronchial section on ciliary beating frequency.

Malaria is one the world’s most devastating diseases. Several classes of drugs are used to treat malaria. Artemisinin combination therapy is the first line treatment of uncomplicated malaria. The artemisinin derivative, artemisone in conjunction with the Pheroid® drug delivery system, is the focus of this thesis. The impact of the Pheroid® on the bioavailability of artemisone was evaluated in vervet monkeys. The resulting artemisone plasma levels were much lower (Cmax of 47 and 114 ng/mL for reference and Pheroid® test formulations respectively) than expected for the dosages administered (60 mg/kg). The Pheroid® improved the pharmacokinetic profile of artemisone in a clinically significant manner. The metabolism of artemisone was assessed in vitro by using human and monkey liver and intestinal microsomes, and recombinant CYP3A4 enzymes. The Pheroid® inhibits the microsomal metabolism of artemisone. In addition, there is a species difference in artemisone metabolism between man and monkey since the in vitro intrinsic clearance of the reference formulation with monkey liver microsomes is ~8 fold higher in the monkey liver microsomes compared to the human liver microsomes and the estimated in vivo hepatic clearance for the monkey is almost twofold higher than in humans. Artemisone has potent antimalarial activity. Its in vitro efficacy was approximately twofold higher than that of either artesunate or dihydroartemisinin when evaluated against P. falciparum W2, D6, 7G8, TM90-C2B, TM91-C235 and TM93-C1088 parasite strains. The Pheroid® drug delivery system did not improve or inhibit the in vitro efficacy of artemisone or DHA. Artemisone (reference and Pheroid® test formulations) and metabolite M1 abruptly arrested the growth of P. falciparum W2 parasites and induced the formation of dormant ring stages in a manner similar to that of DHA. Interaction of artemisone with the p-glycoprotein (p-gp) efflux transporter was investigated. Artemisone stimulates ATPase activity in a concentration-dependent manner, whereas the Pheroid® inhibited this p-gp ATPase activity. P-gp ATPase activity stimulation was fourfold greater in human than cynomolgus monkey MDR1 expressed insect cell membranes. Artemisone alone and artemisone entrapped in Pheroid® vesicles showed moderate apical to basolateral and high basolateral to apical permeability (Papp) across Caco-2 cells. The Papp efflux ratio of artemisone and artemisone entrapped in Pheroid® vesicles were both >5, and decreased to ~1 when the p-gp inhibitor, verapamil, was added. Therefore, artemisone is a substrate for mammalian p-gp. The cytotoxic properties of Pheroid® on Caco-2 cells were assessed and the pro-Pheroid® seems to be non-toxic at concentrations of 1.25%. Vervet monkey plasma caused antibody-mediated growth inhibition of P. falciparum. Heat inactivated or protein A treatment proved useful in the elimination of the growth-inhibitory activity of the drug-free plasma. Plasma samples containing artemisone could not be analysed by the ex-vivo bioassay method. The dual labelling ROS assay did not prove to be useful in the evaluation of ROS production by artemisone and the Pheroid® delivery system. In conclusion, entrapment of artemisone in the Pheroid® delivery system improves the pharmacokinetic properties of artemisone, but does not improve or inhibit its antimalarial efficacy in vitro. The Pheroid® inhibited both the microsomal metabolism of artemisone and P-gp ATPase activity and was shown to be non-toxic at clinically usable concentrations. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Malaria is one the world’s most devastating diseases. Several classes of drugs are used to treat malaria. Artemisinin combination therapy is the first line treatment of uncomplicated malaria. The artemisinin derivative, artemisone in conjunction with the Pheroid® drug delivery system, is the focus of this thesis. The impact of the Pheroid® on the bioavailability of artemisone was evaluated in vervet monkeys. The resulting artemisone plasma levels were much lower (Cmax of 47 and 114 ng/mL for reference and Pheroid® test formulations respectively) than expected for the dosages administered (60 mg/kg). The Pheroid® improved the pharmacokinetic profile of artemisone in a clinically significant manner. The metabolism of artemisone was assessed in vitro by using human and monkey liver and intestinal microsomes, and recombinant CYP3A4 enzymes. The Pheroid® inhibits the microsomal metabolism of artemisone. In addition, there is a species difference in artemisone metabolism between man and monkey since the in vitro intrinsic clearance of the reference formulation with monkey liver microsomes is ~8 fold higher in the monkey liver microsomes compared to the human liver microsomes and the estimated in vivo hepatic clearance for the monkey is almost twofold higher than in humans. Artemisone has potent antimalarial activity. Its in vitro efficacy was approximately twofold higher than that of either artesunate or dihydroartemisinin when evaluated against P. falciparum W2, D6, 7G8, TM90-C2B, TM91-C235 and TM93-C1088 parasite strains. The Pheroid® drug delivery system did not improve or inhibit the in vitro efficacy of artemisone or DHA. Artemisone (reference and Pheroid® test formulations) and metabolite M1 abruptly arrested the growth of P. falciparum W2 parasites and induced the formation of dormant ring stages in a manner similar to that of DHA. Interaction of artemisone with the p-glycoprotein (p-gp) efflux transporter was investigated. Artemisone stimulates ATPase activity in a concentration-dependent manner, whereas the Pheroid® inhibited this p-gp ATPase activity. P-gp ATPase activity stimulation was fourfold greater in human than cynomolgus monkey MDR1 expressed insect cell membranes. Artemisone alone and artemisone entrapped in Pheroid® vesicles showed moderate apical to basolateral and high basolateral to apical permeability (Papp) across Caco-2 cells. The Papp efflux ratio of artemisone and artemisone entrapped in Pheroid® vesicles were both >5, and decreased to ~1 when the p-gp inhibitor, verapamil, was added. Therefore, artemisone is a substrate for mammalian p-gp. The cytotoxic properties of Pheroid® on Caco-2 cells were assessed and the pro-Pheroid® seems to be non-toxic at concentrations of 1.25%. Vervet monkey plasma caused antibody-mediated growth inhibition of P. falciparum. Heat inactivated or protein A treatment proved useful in the elimination of the growth-inhibitory activity of the drug-free plasma. Plasma samples containing artemisone could not be analysed by the ex-vivo bioassay method. The dual labelling ROS assay did not prove to be useful in the evaluation of ROS production by artemisone and the Pheroid® delivery system. In conclusion, entrapment of artemisone in the Pheroid® delivery system improves the pharmacokinetic properties of artemisone, but does not improve or inhibit its antimalarial efficacy in vitro. The Pheroid® inhibited both the microsomal metabolism of artemisone and P-gp ATPase activity and was shown to be non-toxic at clinically usable concentrations. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

En marge d'expériences actuelles visant à développer une méthodologie analytique sur la pharmacocinétique-pharmacodynamique de la N-acétyl-cystéine (NAC) en prévention de la néphropathie liée à l'exposition aux substances de contraste (NESC), une mesure de la clairance des substances de contraste a été mise au point comme marqueur de filtration glomérulaire (FG) étant donné que celles-ci sont totalement éliminées par FG. Ainsi, la mesure de la FG a été déterminée par la clairance de l'iohexol, substance de contraste utilisée en imagerie médicale. L'originalité de ce projet est triple: (1) mesurer la clairance de l'iohexol (Omnipaque) chez des patients recevant également de l'iodixanol (Visipaque), substance de contraste de plus en plus utilisée; (2) explorer la mesure de la clairance d'iodixanol et (3) utiliser la spectrométrie de masse couplée à la chromatographie liquide, qui depuis les dernières années s'est taillée une place de plus en plus importante, pour le dosage de l'iohexol et de l'iodixanol. Le projet actuel s'est déroulé chez 17 sujets avec divers niveaux de fonction rénale devant subir des examens d'imagerie avec des substances de contraste. Une dose-traceur d'iohexol (5 ml) a été co-administrée avec l'iodixanol (environ 95 ml). Des spécimens sanguins ont été obtenus 0, 1, 2, 3, 4, 8 et 24 heures post-imagerie pour mesurer les clairances de l'iohexol et de l'iodixanol. Le comportement des autres marqueurs conventionnels de FG, soit le taux créatinine plasmatique et la clairance de la créatinine, ainsi que la clairance de la cystatine C et la clairance d'iodixanol ont été comparés à la clairance d'iohexol. Par conséquent, un protocole scientifique par HPLC-MSD Tof a été développé afin de séparer et de quantifier les molécules iohexol et iodixanol co-administrées dans le plasma des sujets. Les mesures des taux plasmatiques de ces deux molécules ont permis de déterminer par des calculs pharmacocinétiques que la clairance de l'iohexol discrimine bien la fonction rénale des sujets avec une fonction rénale normale de ceux avec une fonction rénale diminuée. De plus, il a été démontré qu'une seule mesure post-4 heures est suffisante pour diagnostiquer l'état de la fonction rénale d'un patient qui a subi une intervention demandant une exposition aux substances de contraste. Les corrélations entre la clairance de l'iohexol et d'autres marqueurs conventionnels de FG ainsi que celle de l'iodixanol ont illustré que la clairance de la créatinine calculée soit par l'équation MDRD (r = 0,714 et p = 0,001) ou par Cockcroft et Gault (r = 0,518 et p = 0,033) et la clairance de la cystatine C (r = 0,671 et p = 0,003) corrèlaient de manière significative avec l'étalon d'or, soit la clairance de l'iohexol. C'est pourquoi, il pourrait être possible de se fier à la mesure de la clairance de l'iohexol comme meilleur marqueur de FG afin de prévenir, de diagnostiquer et de traiter la NESC. De plus, des expériences scientifiques en recherche fondamentale pourront enfin être menées pour déterminer la relation pharmacodynamique- pharmacocinétique de la N-acétylcystéine dans la prévention de la NESC à l'aide de la mesure de la clairance de l'iohexol comme marqueur fiable de la FG. Enfin, les mécanismes d'action qui interviennent dans la NESC pourront être mieux évalués.

[pt] O fluxo intenso de mercadorias entre países é uma característica marcante da globalização. Isto ocorre porque cada vez mais empresas procuram instalar unidades produtivas próximas aos mercados consumidores, enquanto que seus fornecedores situam-se em vários países. Conseqüentemente, cresce a importância do planejamento da movimentação de materiais dentro de um sistema logístico internacional. Decisões relativas à escolha dos meios de transportes, dos terminais multi-modais de carga, dos equipamentos para manuseio, das estratégias de armazenagem, da embalagem e unitização dos produtos, e de sistemas de informação, são estratégicas para o sucesso do projeto de rede. As cadeias de suprimentos projetadas pelas multinacionais automotivas são um dos os maiores exemplos de redes de fluxos internacionais de produtos. Neste contexto, a presente dissertação realiza uma análise da logística de importação de partes e peças amparadas pelos conceitos de produção, embalagem e transporte Completely-Knocked-Down (CKD) e Part-By- Part (PBP), através do estudo de caso dos projetos dos automóveis Classe A e Classe C, produzidos pela montadora DaimlerChrysler do Brasil na sua unidade produtiva localizada na cidade de Juiz de Fora. / [en] The increase of material flows between countries is a strong characteristic of globalization. It happens because more and more companies are installing production units near their main markets and their suppliers` plants can be in located in different sites around the world. Therefore the importance of supply chain planning increases into the logistics system. Decisions about warehousing, transport modes, inter-modal terminals, handling equipments, packaging, unitization and information systems are strategic for the success of the network project. The multinational automakers are one of the biggest players of the international material flow. Within this context, the present master`s thesis proposes a supply chain analysis of automotive import parts involving Completely-Knocked-Down (CKD) and Part-By-Part (PBP) production, packaging and transport concepts, by the analysis of a case study of A-Class and C-Class logistics project models assembled by DaimlerChrysler in Juiz de Fora city (Brazil).