The main goal of this research is to understand molecular mechanisms of GAA/TTC-associated genetic instability in a model eukaryotic organism, S. cerevisiae. We demonstrate that expanded GAA/TTC repeats represent a threat to eukaryotic genome integrity by triggering double-strand breaks and gross chromosomal rearrangements. The fragility potential strongly depends on the length of the tracts and orientation of the repeats relative to the replication origin and to block replication fork progression. MutSbeta complex and endonuclease activity of MutLalpha play an important role in facilitation of fragility. In addition to GAA/TTC triplex forming repeats, non-GAA polypurine polypyrimidine mirror repeats that are prone to the formation of similar structures were found to be hotspots for rearrangements in humans and other model organisms. These include H-DNA forming sequences located in the major breakpoint cluster region at BCL2, intron 21 of PKD1, and promoter region of C-MYC. Lastly, we have investigated the effect of the triplex-binding small molecules, azacyanines, on GAA-mediated fragility using the chromosomal arm loss assay. We have found that in vivo, azacyanines stimulate (GAA/TTC)-mediated arm loss in a dose dependent manner in actively dividing cells. Azacyanines treatment enhances the GAA-induced replication arrest. We discovered that also, azacyanines at concentrations that induce fragility also inhibit cell growth. Over 60% of yeast cells are arrested at G2/M stage of the cell cycle. This implies an activation of DNA-damage checkpoint response.

Introduction: This thesis examined the impact of PTSD with Major Depressive Disorder on PTSD severity among Toronto Transit Commission employees who were exposed to a workplace traumatic event, and also the predictors of PTSD severity, mental health treatment seeking, and return to work over the six month study period. Methods: This study utilized data that was collected prospectively from the APT study participants. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale respectively. Results: PTSD without MDD (N=29) and PTSD with MDD (N=37) groups were compared. The variables: depression severity (p=0.01), female (p=0.01), non-Caucasian (p=0.01), workplace related stress (p=0.02), and lifetime trauma (p=0.01) significantly predicted PTSD severity. The BPI group significantly predicted mental health treatment seeking (p<0.01) after controlling other variables. Conclusion: This study highlights the substantial risk for experiencing greater PTSD severity after a workplace traumatic event in TTC employees.

Introduction: This thesis examined the impact of PTSD with Major Depressive Disorder on PTSD severity among Toronto Transit Commission employees who were exposed to a workplace traumatic event, and also the predictors of PTSD severity, mental health treatment seeking, and return to work over the six month study period. Methods: This study utilized data that was collected prospectively from the APT study participants. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale respectively. Results: PTSD without MDD (N=29) and PTSD with MDD (N=37) groups were compared. The variables: depression severity (p=0.01), female (p=0.01), non-Caucasian (p=0.01), workplace related stress (p=0.02), and lifetime trauma (p=0.01) significantly predicted PTSD severity. The BPI group significantly predicted mental health treatment seeking (p<0.01) after controlling other variables. Conclusion: This study highlights the substantial risk for experiencing greater PTSD severity after a workplace traumatic event in TTC employees.

DNA repetitive sequences capable of adopting non-B DNA structures are a potent source of instability in eukaryotic genomes. They are strong inducers of chromosomal fragility and genome rearrangements that cause various hereditary diseases and cancers. In addition, a subset of repeats also has an ability to expand, which leads to more than 20 human genetic diseases that are collectively known as repeat expansion diseases. However, the mechanisms underlying the potential of these structure-prone motifs to break and expand are largely unknown. In this study, a systematic genome-wide screen was employed in yeast Saccharomyces cerevisiae to investigate the contributing factors of the instability of two representative non-B DNA-forming repeats: the triplex-adopting GAA/TTC tracts and the inverted repeats that can form hairpin and cruciform structures. The GAA/TTC screen revealed that DNA replication and transcription initiation are the two major pathways governing the GAA/TTC stability in yeast, as corresponding mutants strongly induce both fragility and large-scale expansions of the repeats. The inverted repeats screen and follow-up experiments revealed that both replication-dependent and -independent pathways are involved in maintaining the stability of palindromic sequences. We propose that similar mechanisms could operate in the human cells to mediate the deleterious metabolism of GAA and inverted repeats.

In order to be compliant with the Basel regulations, banks need to compute two probabilities of default (PDs): point-in-time (PIT) and through-the-cycle (TTC). The aim is to explain fluctuations in the rating system, which are expected to be affected by systematic and idiosyncratic factors. Being able to, in an objective manner, determine whether the rating system is taking the business cycle - i.e the systematic factors - into account when assigning a credit rating to an obligor is useful in order to evaluate PD-models. It is also necessary for banks in order to use their own risk parameters and models instead of standardized models, which is desirable for most banks as it could lower capital requirements. This thesis propose a new measure for the degree of PIT-ness. This measure aims to be especially useful when examining a low default portfolio. The proposed measure is built on a markovian approach of the credit rating system. In order to find a suitable measure for a low default portfolio, the proposed measure takes into account credit rating migrations, the seasonal component of the business cycle and time series analysis. An analysis were performed between two different credit portfolios in order to interpret results. The results demonstrated that the degree of PIT-ness was lower in a low default portfolio in comparison with a sampled portfolio which displayed a greater amount of rating migrations with a larger magnitude. The importance of considering relevant macroeconomic variables to represent the business cycle was mentioned amongst the most important factors to consider in order to receive reliable results given the proposed measure. / För att uppfylla Basel regelverken behöver banker beräkna två sannolikheter för fallissemang (PD): point-in-time (PIT) och through-the-cycle (TTC). Målet är att förklara fluktuationer i betygssystemet, som förväntas påverkas av systematiska och idiosynkratiska faktorer. Att på ett objektivt sätt kunna avgöra om betygssystemet tar hänsyn till affärscykeln - dvs de systematiska faktorerna - när man tilldelar en kredittagare ett kreditbetyg är användbart för att utvärdera PD-modeller. Detta är också nödvändigt för att banker ska få använda sina egna riskparametrar och modeller istället för standardiserade modeller, vilket är önskvärt för de flesta banker eftersom det kan sänka kapitalkraven. Denna avhandling föreslår ett nytt mått för att mäta graden av PIT-ness. Detta mått syftar till att vara särskilt användbart när man utvärderar en kreditportfölj med få fallissemang. Det föreslagna måttet är byggt på en Markov tillämpning på kreditbetygssystemet. För att hitta ett lämpligt mått för en kreditportfölj med få fallissemang, tar det föreslagna måttet hänsyn till kreditbetygsmigrationer, säsongskomponenten i affärscykeln och tidsserieanalys. En analys utfördes mellan två olika kreditportföljer för att tolka resultaten. Resultaten visade att graden av PIT-ness var lägre i en kreditportfölj med få fallissemang jämfört med en testportfölj som uppvisade en större mängd kreditbetygsmigrationer med en större magnitud. Vikten av att beakta relevanta makroekonomiska variabler för att representera affärscykeln nämndes bland de viktigaste faktorerna att beakta för att få tillförlitliga resultat givet det föreslagna måttet.

Nos programas de melhoramentos de soja as progênies endogâmicas são frequentemente avaliadas como possíveis cultivares. O estudo da estrutura da variação genética entre progênies de diferentes gerações de autofecundação depende da ação dos locos envolvidos e da variação do caráter sob estudo. Em soja o caráter produção de grãos (PG) é considerado o de maior importância econômica e destaca-se por apresentar herança quantitativa e ser altamente influenciada pelo ambiente. As estratégias de seleção utilizadas para o desenvolvimento de cultivares em soja poderiam ser otimizadas através do estudo da importância relativa dos componentes de variância, particularmente a proporção de variação devida à interação não alélica (epistasia). Com o objetivo de estudar a variação epistática e sua interação com ambientes (locais) para a produção de grãos em soja utilizou-se o delineamento "Triple Test Cross Modificado" (TTC) de JINKS, PERKINS e BREESE (1969). Uma amostra de 32 linhagens (Pi) derivadas de um cruzamento biparental foi cruzada com duas linhagens divergentes (L1 e L2) contrastantes para PG, derivadas da mesma população (testadores). Os experimentos de avaliação foram conduzidos no ano agrícola de 2006/2007 em dois locais (Piraciacaba e Anhembi) em delineamentos em látice triplo 10 x 10. Os tratamentos correspondiam aos 32 cruzamentos Pi x L1, 32 cruzamentos Pi x L2, 34 linhas puras (32 Pi + 2 testadores) e duas testemunhas comerciais. De acordo com a metodologia utilizada foram estudados os contrastes ( i 2i 1i P L L - + ) para avaliar a ocorrência de epistasia. Os resultados das análises individuais mostraram que a epistasia afetou a expressão da produção de grãos em ambos os locais. A análise conjunta permitiu detectar significância para locais, epistasia e interação epistasia por locais, indicando que a produção de grãos em soja é afetada pela interação não alélica (epistasia) e que esta não é consistente entre locais. O estudo do contraste ( i 2i 1i P L L - + ) das médias individuais nas análises por local e na análise conjunta indicou haver contribuição diferencial dos genótipos para a epistasia. Os resultados gerais indicam que a epistasia pode ser um componente importante para a expressão da produção de grãos de soja e, consequentemente, esta deveria ser incluída nos modelos para a decomposição dos componentes da variância genética. / In soybean breeding programs the selfing progenies are generally evaluated as possible cultivars. The study of the structure of the genetic variation among progenies in different generations of selfing depends upon the action of the loci involved and the variability of the trait under study. In soybeans, grain yield is the most important trait and it is characterized by a quantitative inheritance and highly influenced by the environment. The selection strategies used for the development of soybean cultivars could be optimized through the study of the relative importance of the variance components, in particular the proportion of the non-allelic interaction component (epistasis). In order to study the epistatic variation and its interaction with locations for grain yield in soybeans the "Modified Triple Test Cross" (TTC) method (JINKS, PERKINS e BREESE, 1969) was used. A sample of 32 inbred lines (Pi) derived from a single cross were crossed with two divergent inbred lines (L1 e L2) of the same population (testers). The experiments were carried out in the 2006/2007 growing season in two locations (Piracicaba and Anhembi) in a 10x10 triple lattice design. Entries consisted of the 32 Pi x L1 crosses, 32 Pi x L2 crosses, 34 lines (Pi + 2 testers) and 2 commercial checks. Following the methodology, the contrasts ( i 2i 1i P L L - + ) were studied in order to evaluate the occurrence of epistasis. General results showed that epistasis affected grain yield in soybeans in both locations. Significance for locations, epistasis and epistais by locations interactions were also detected in the joint analysis of variance, indicating that grain yield in soybeans is affected by the non-allelic interaction (epistasis) and that the epistasis is not consistent in different locations. A study of the contrast ( i 2i 1i P L L - + ) of individual means for each location and in the joint analyses indicated the occurrence of differential contribution of the genotypes for the epistasis. General results had demonstrated that epistasis could be an important component for the expression of grain yield in soybeans and consequently it should be included in the model for the partition of the genetic components of variance.

Nos programas de melhoramentos de soja as progênies endogâmicas são frequentemente avaliadas como possíveis cultivares. O estudo da estrutura da variação genética entre progênies de diferentes gerações de autofecundação depende da ação dos locos envolvidos e da variação do caráter sob estudo. Em soja o caráter produção de grãos (PG) é considerado o de maior importância econômica e destaca-se por apresentar herança quantitativa e ser altamente influenciada pelo ambiente. As estratégias de seleção utilizadas para o desenvolvimento de cultivares em soja poderiam ser otimizadas através do estudo da importância relativa dos componentes de variância, particularmente a proporção de variação devida à interação não alélica (epistasia). Com o objetivo de estudar a variação epistática e sua interação com ambientes (locais) para a produção de grãos em soja utilizou-se o delineamento "Triple Test Cross Modificado" (TTC) de JINKS, PERKINS e BREESE (1969). Uma amostra de 32 linhagens (Pi) derivadas de um cruzamento biparental foi cruzada com duas linhagens divergentes (L1 e L2) contrastantes para PG, derivadas da mesma população (testadores). Os experimentos de avaliação foram conduzidos no ano agrícola de 2006/2007 em dois locais (Piraciacaba e Anhembi) em delineamentos em látice triplo 10 x 10. Os tratamentos correspondiam aos 32 cruzamentos Pi x L1, 32 cruzamentos Pi x L2, 34 linhas puras (32 Pi + 2 testadores) e duas testemunhas comerciais. De acordo com a metodologia utilizada foram estudados os contrastes ( i 2i 1i P L L - + ) para avaliar a ocorrência de epistasia. Os resultados das análises individuais mostraram que a epistasia afetou a expressão da produção de grãos em ambos os locais. A análise conjunta permitiu detectar significância para locais, epistasia e interação epistasia por locais, indicando que a produção de grãos em soja é afetada pela interação não alélica (epistasia) e que esta não é consistente entre locais. O estudo do contraste ( i 2i 1i P L L - + ) das médias individuais nas análises por local e na análise conjunta indicou haver contribuição diferencial dos genótipos para a epistasia. Os resultados gerais indicam que a epistasia pode ser um componente importante para a expressão da produção de grãos de soja e, consequentemente, esta deveria ser incluída nos modelos para a decomposição dos componentes da variância genética. / In soybean breeding programs the selfing progenies are generally evaluated as possible cultivars. The study of the structure of the genetic variation among progenies in different generations of selfing depends upon the action of the loci involved and the variability of the trait under study. In soybeans, grain yield is the most important trait and it is characterized by a quantitative inheritance and highly influenced by the environment. The selection strategies used for the development of soybean cultivars could be optimized through the study of the relative importance of the variance components, in particular the proportion of the non-allelic interaction component (epistasis). In order to study the epistatic variation and its interaction with locations for grain yield in soybeans the "Modified Triple Test Cross" (TTC) method (JINKS, PERKINS e BREESE, 1969) was used. A sample of 32 inbred lines (Pi) derived from a single cross were crossed with two divergent inbred lines (L1 e L2) of the same population (testers). The experiments were carried out in the 2006/2007 growing season in two locations (Piracicaba and Anhembi) in a 10x10 triple lattice design. Entries consisted of the 32 Pi x L1 crosses, 32 Pi x L2 crosses, 34 lines (Pi + 2 testers) and 2 commercial checks. Following the methodology, the contrasts ( i 2i 1i P L L - + ) were studied in order to evaluate the occurrence of epistasis. General results showed that epistasis affected grain yield in soybeans in both locations. Significance for locations, epistasis and epistais by locations interactions were also detected in the joint analysis of variance, indicating that grain yield in soybeans is affected by the non-allelic interaction (epistasis) and that the epistasis is not consistent in different locations. A study of the contrast ( i 2i 1i P L L - + ) of individual means for each location and in the joint analyses indicated the occurrence of differential contribution of the genotypes for the epistasis. General results had demonstrated that epistasis could be an important component for the expression of grain yield in soybeans and consequently it should be included in the model for the partition of the genetic components of variance.

Extensive research has been performed on the interaction of dithiocarbonates (xanthate) with a wide variety of substrates. This study the focuses on the interaction of trithiocarbonates (TTC) with pyrite and copper. The mechanism of adsorption of the xanthate is compared to that of the TTC. For the xanthate to adsorb it is necessary for an oxidant to be present, since xanthate adsorbs via charge transfer processes (electrochemical processes). It was found by the use of cyclic voltammetry and contact angle measurements that collector adsorption of the TTC can occur in both oxidising and reducing (thus the absence of an oxidant) conditions. Neither the TTC monomer nor the dimer could be detected on the surface by the use of Raman spectroscopy. The collector species on the surface was the TTC decomposition products namely the thiol or thiolate. Electrochemical impedance spectroscopy (EIS) confirmed that the TTC can interact under oxidising and reducing conditions. EIS showed that the rate of adsorption of the collector species for anodic currents increases relatively to the rate of adsorption for cathodic currents. Different adsorption mechanisms are realised for the different polarisation conditions. It is postulated that the TTC species serves as an intermediate for the adsorption of the thiol or thiolate on the surface, ultimately rendering the surface hydrophobic. Decomposition tests, performed by employing UV/Vis spectroscopy, indicated that the TTC is very unstable between a pH of 4 and 11. The thiol or thiolate however does not readily adsorb onto the substrates (indicated by the EIS measurements). Microflotation tests confirmed the thiolate’s inability to render pyrite hydrophobic. The microflotation tests also indicated that the TTC became less effective in recovering pyrite after it was left to decompose for a couple of hours. / Dissertation (MSc (Metallurgy))--University of Pretoria, 2008. / Materials Science and Metallurgical Engineering / unrestricted

Dans un contexte de navigation visuelle en environnement ouvert et dynamique, la détection d'obstacles constitue un élément indispensable. Dans cette thèse, nous nous intéressons à la caractérisation des obstacles par le temps avant collision (TTC). Ayant montré que ce TTC peut être calculé directement dans une image à l'aide de l'échelle intrinsèque, nous avons mis au point un détecteur ainsi qu'un algorithme de suivi invariant au changement d'échelle et adapté à un environnement urbain. Ce détecteur permet d'extraire des régions d'intérêt appelées segments de crête correspondant à des formes contrastées et rectilignes dans l'image. Le suivi de ces régions d'intérêt est fondé sur un filtre à particules et permet de mesurer la variation d'échelles afin d'estimer le TTC. Enfin, nous avons étudié deux applications de navigation visuelle d'un véhicule telles que l'arrêt du véhicule avant collision et un système d'évitement réactif d'obstacles bayésien.

According to NCHRP Report 493, there are five major left turn signal indications for permitted operations in the United States. They are: Circular Green (CG), Flashing Circular Red (FCR), Flashing Red Arrow (FRA), Flashing Circular Yellow (FCY) and Flashing Yellow Arrow (FYA). The main goal of this thesis is to study the driver behavior and analyze safety of drivers for different left turn indications using a real-time driving simulator. Different signal indications alter driver behavior which influences velocity and acceleration profiles. These profiles influence vehicular emissions and hence need to be studied as well. For this purpose, different scenarios are implemented in the driving simulator. Data is analyzed using Microsoft Excel, JMP Statistical tool and MATLAB. Safety of drivers is analyzed with respect to the parameter "Time to Collision (TTC)" which is directly obtained from simulator data. Vehicular emissions and fuel consumption are calculated using VT-Micro microscopic emissions model. Graphs are plotted for TTC and total emissions. Results indicate that for a day-time scenario, FCY and FYA are the most suitable left-turning indications whereas FCR and FRA are most suitable for a night-time scenario. / Master of Science