VictorJuiz/thesis huggingface dataset:
The Study of Inhomogeneous Cosmologies Through Spacetime Matchings

Our universe is inherently inhomogeneous yet it is common in the study of cosmology to model our universe after the homogeneous and isotropic Friedmann-Lemaıtre-Roberson-Walker (FLRW) model. In this thesis spacetime matchings are applied to investigate more general inhomogeneous cosmologies. The Cheese Slice universe, constructed from matching together FLRW and Kasner regions satisfying the Darmois matching conditions, is used as a prime example of an inhomogeneous cosmology. Some observational consequences of this model are presented. The lookback time verses redshift relation is calculated using a numerical algorithm and it is shown that the relative thickness of the Kasner regions have the greatest impact on anisotropies an observer would see. The number of layers and distribution of layers play a smaller role in this regard. The relative thickness of the Kasner slice should be on the order of one ten thousandth the thickness of the FLRW regions to have the anisotropies fall within the observed CMB limit. The approach to the singularity of a spacetime matching is examined. A criterion is presented for a matched spacetime to be considered Asymptotically Velocity Term Dominated (AVTD). Both sides of the matching must be AVTD and each leaf of the respective foliations mush match as well. It is demonstrated that the open and flat Cheese Slice universe are both AVTD and the singularity is also of AVTD type. The Cheese Slice model is then examined as a braneworld construction. The possibility of a Cheese Slice brane satisfying all the energy conditions is shown. However, the embedding of such a brane into a symmetric bulk is non-trivial. The general embedding of a matched spacetime into a bulk is investigated using a Taylor series approximation of the bulk. It is found that the energy-momentum tensor of such a brane cannot have discrete jumps if the embedding does not have a corner. A 3+1+1 decomposition of the bulk spacetime is then carried out. With the spacetime being deconstructed along two preferred timelike hypersurfaces, this becomes a natural environment to discuss the matching of branes. We find that there are conditions on the matter content of the branes to be matched if an observer on the brane is to see the matching surface as a boundary surface with no additional stress energy. Matching more than two bulks is also examined and shown to allow for more general brane configurations.

Keywords: Cosmology
Advisor: Dyer, Charles C.
Sri Lankan Tamil Diaspora: Contextualizing Pre-migration and Post- migration Traumatic Events and Psychological Distress

The objective of this study was to generate a deeper understanding of the influence of pre- and post-migration traumatic experiences on refugees’ psychological distress, including historical, political and social factors. This dissertation used a multi-method design to examine the impact of trauma on the psychological well-being of refugees. Further, the design included a qualitative component to provide a contextual framework for understanding refugee psychological distress that is not limited to an analysis of a disease model alone but by also making connections to important historical, social and political events. Post-Colonial, Refugee, Trauma and Feminist theories are used as analytic lenses to explain the social structures and events contributing to refugees’ pre- and post-migration traumatic events, and psychological distress. This was an international study that spanned two continents. Sampling included 50 Sri Lankan Tamil refugee participants who lived in Chennai, India and 50 Sri Lankan refugees in Toronto, Canada. Inclusion criteria included a residency period of the last 12 months in either of the sampling sites, and participants 18 years of age or older. Participants from Toronto were recruited through social service agencies and associations, and participants from Chennai were recruited from refugee camps, and the Organization for Elam Refugee Rehabilitation. Tamil versions of the Harvard Trauma Questionnaire, the Post-Migration Living Difficulties Questionnaire, and the Symptoms Check List – 90R were utilized to measure participants’ pre- and post-migration traumatic events and psychological distress. The Harvard Trauma Questionnaire contained qualitative open-ended questions to triangulate the quantitative data in identifying and exploring the impact of contextual influences. Results showed that post-migration traumatic event scores positively predicted psychological distress, and refugee claimants living in Canada had the highest scores on pre-migration and post-migration scores. The qualitative analysis revealed themes related to civil war and resettlement as significant issues. Implications of these findings support the development of a multi-level approach within social work practice which emphasizes contextual issues, focuses on individuals, and promotes social advocacy. Recommendations for future research point to conducting longitudinal studies to assess the cumulative effects of historical, social and political factors on refugees and identify resiliencies that mobilize their capacity to survive.

Keywords: 0452
0347
Advisor: Alaggia, Ramona
OH-initiated Heterogeneous Oxidation of Atmospheric Organic Aerosols

The chemical aging of organic aerosols by OH-initiated heterogeneous oxidation was investigated using both model organic and ambient aerosol particles. Organic aerosol particles were exposed to OH radicals in an aerosol flow tube and the modification of their chemical composition and particle properties was studied. Overall, this work has shown that OH-initiated heterogeneous oxidation enhanced the degree of oxidation and the Cloud Condensation Nucleus (CCN) activity of organic aerosol particles for equivalent OH exposure timescales of a few days to a week. Aerosol Mass Spectrometer (AMS) measurements showed that the heterogeneous uptake kinetics of OH radicals onto model primary organic aerosols was efficient. The heterogeneous reaction of organic aerosols with OH led to the production of high molecular weight particle-phase species with the addition of multiple oxygenated functional groups. These results were consistent with the observed increase in particle density with OH exposure. With the exception of solid organic aerosols, the particle volume and mass of organic particles were reduced by less than 20% from OH oxidation at high OH exposures due to volatilization of particle-phase reaction products. The degree of oxidation of the organic fraction of urban ambient aerosols was significantly enhanced for an equivalent atmospheric OH exposure time of 4 days for a daily average atmospheric OH concentration of 2×106 cm-3. Ambient aerosol particles sampled from a sparsely populated, forested region were initially more oxygenated than the urban aerosol particles and did not become more oxidized from reaction with OH radicals. The modification of the hygroscopicity of model primary and secondary organic aerosols from chemical aging was investigated by measuring the CCN activity of organic aerosols exposed to OH radicals. Primary organic aerosols, initially CCN inactive, became as CCN active as secondary organic aerosols due to heterogeneous reaction, where surface tension reduction played a major role. The CCN activity for model secondary organic aerosols was also enhanced due to OH oxidation, but changes were less dramatic than for the model primary organic aerosols.

Keywords: atmospheric chemistry
hydroxyl radicals
Advisor: Abbatt, Jonathan P. D.
Categories and Evaluation Bias in Valuation of Technological Innovation

This dissertation examines the perceptual bias of investors and securities analysts (the “audience” in the stock market) in their valuation of public firms’ innovative activities. I suggest that such bias occurs because the audience views a firm’s innovation through the prism of the firm’s categorization in product markets – its industry category – which may only loosely conform to the technological interrelationship among firms in knowledge space. I explore theoretically the conditions under which evaluation bias is most likely to occur – notably, due to innovations that defy the existing categorical structure used by the audience. Based on this theoretical framework, I develop hypotheses for empirical tests. I first argue that both technological opportunities and technological threats residing outside a firm’s industry are more likely to be underestimated by the stock market than those residing within the industry. In a sample of large U.S. manufacturing firms covering the years 1980 through 2000, I collected patent data to reflect innovative activities of firms. I compare the effect of a firm’s innovative activities on its current market valuation and its future cash flows. Consistent with my predictions, I find that firms capitalizing on cross-industry opportunities are more likely to be undervalued, while firms facing cross-industry technological competition are more likely to be overvalued. I further argue that reliance on categorical identity for information cues may reduce the audience’s ability to adequately assess the value-relevance of innovations that deviate from the technological norm in an industry. By analyzing the absolute forecast errors in security analysts’ reports, I find confirming evidence that deviant innovations increase the forecast bias. I further argue and demonstrate that such bias is less prevalent for diversified firms and in industries with less stable categorical “norms,” two conditions in which the audience is less likely to rely on categorical information and more likely to employ firm-specific information. Finally, I discuss the contribution and implication of the findings to studies of categorization and value-relevance of technological innovations.

Keywords: valuation
innovation
Advisor: Silverman, Brian S.
Vascular and Metabolic Risk Factors, Carotid Atherosclerosis and Vascular Cognitive Impairment in a First Nations Population

The objectives of the thesis were to examine the associations between vascular and metabolic risk factors, carotid atherosclerosis and cognitive function in a Canadian First Nations population. Eligible individuals were ≥18 years and with First Nations status who had undergone cognitive function assessment by the Clock Drawing Test (CDT) and the Trail Making Test Parts A and B. Parts A and B were combined into an executive function score (TMT-exec). Anthropometric, vascular and metabolic risk factors were assessed by interview, clinical examinations and blood tests. Doppler ultrasonography assessed carotid atherosclerosis (carotid stenosis, plaque volume). For the 190 individuals with TMT-exec scores, obese individuals were at a 4-fold increased risk for lowered cognitive performance compared to those who were not obese (odds ratio [OR]: 3.77, 95% confidence interval [CI]: 1.46-9.72). Those having an increased waist circumference also had 5 times the risk compared to those without an increased waist circumference (OR: 5.41, 95% CI: 1.83-15.99). Individuals having the metabolic syndrome were at a 4-fold increased risk compared to those without the metabolic syndrome (OR: 3.67, 95% CI: 1.34-10.07). No other cardiovascular risk factors were associated and no associations were shown for the CDT. For TMT-exec only, individuals with elevated levels of left (LCS) and total carotid stenosis (TCS) were less likely to demonstrate lowered cognitive performance (LCS, OR: 0.47, 95% CI: 0.24-0.96; TCS, OR: 0.40, 95% CI: 0.20-0.80). In structural equation modeling, for every 1-unit change in the anthropometric factor in kg/m2, there was a 0.86-fold decrease in the percent of TCS (p<0.05). The etiology of VCI is vascular and is affected by non-traditional risk factors such as obesity. The health effects of obesity beyond traditional disease endpoints warrants further study. Mild-moderate levels of carotid stenosis are not detrimental to cognitive functioning and may additionally include acting as a mediator.

Keywords: Epidemiology
Advisor: Young, Kue
Local Likelihood for Interval-censored and Aggregated Point Process Data

The use of the local likelihood method (Tibshirani and Hastie, 1987; Loader, 1996) in the presence of interval-censored or aggregated data leads to a natural consideration of an EM-type strategy, or rather a local EM algorithm. In the thesis, we consider local EM to analyze the point process data that are either interval-censored or aggregated into regional counts. We speciﬁcally formulate local EM algorithms for density, intensity and risk estimation and implement the algorithms using a piecewise constant function. We demonstrate that the use of the piecewise constant function at the E-step explicitly results in an iteration that involves an expectation, maximization and smoothing step, or an EMS algorithm considered in Silverman, Jones, Wilson and Nychka (1990). Consequently, we reveal a previously unknown connection between local EM and the EMS algorithm. From a theoretical perspective, local EM and the EMS algorithm complement each other. Although the statistical methodology literature often characterizes EMS methods as ad hoc, local likelihood suggests otherwise as the EMS algorithm arises naturally from a local likelihood consideration in the context of point processes. Moreover, the EMS algorithm not only serves as a convenient implementation of the local EM algorithm but also provides a set of theoretical tools to better understand the role of local EM. In particular, we present results that reinforce the suggestion that the pair of local EM and penalized likelihood are analogous to that of EM and likelihood. Applications include the analysis of bivariate interval-censored data as well as disease mapping for a rare disease, lupus, in the Greater Toronto Area.

Keywords: Local likelihood
EMS algorithm
Disease mapping
Lupus
Advisor: Stafford, Jamie
Getting Behind the Grain: The Politics of Producer Opposition to GM Wheat on the Canadian Prairies

On May tenth, 2004 Monsanto announced that it would discontinue breeding and field level research of transgenic Roundup Ready (RR) wheat. This decision was heavily influenced by the widespread rejection of RR wheat by Canadian prairie producers who voiced their opposition through a diverse coalition of rural and urban organizations. With six of the nine member organizations representing rural and farm groups, this research departs from the most common representation of anti-GM movements as being urban and European-centred. This dissertation contrasts the general acceptance of Monsanto’s Roundup Ready canola just five years earlier (in the mid 90s) with the widespread opposition amongst prairie producers to RR wheat. It uses an updated version of the agrarian question and the production of nature thesis to show how capitalist relations are differentiated across place and commodities. The research finds that producer resistance to RR wheat hinged on the specificities of local histories and institutions, cultural conceptions of worth and economic fair treatment, and the character of wheat as a commodity with particular biophysical properties. The research is also concerned with the ways in which producers articulated their resistance with and through discourses of consumption, while at the same time rejecting the attempts made by proponents of RR wheat to relegate them to consuming subjects, who would best register their dissent by voting with their dollars on the market. For many prairie farm organizations, the fate of the family farm is tied up with the future of wheat farming and the capacity of farmers to collectively market their wheat in international markets. Monsanto’s vision for the future of prairie wheat crossed moral and cultural boundaries for producers and organizations that understood themselves as active subjects.

Keywords: agriculture
political economy and ecology
Advisor: Prudham, W. Scott
Modelling and Experimental Results on Stochastic Model Reduction, Protein Maturation, Macromolecular Crowding, and Time-varying Gene Expression.

Gene expression, which connects genomic information to functional units in living cells, has received substantial attention since the completion of The Human Genome Project. Quantitative characterization of gene expression will provide valuable information for understanding the behavior of living cells, and possibilities of building synthetic gene circuits to control or modify the behavior of naturally occurring cells. Many aspects of quantitative gene expression have been studied, including gene expression dynamics and noise in E. coli. The gene expression process itself is stochastic, and modelling approaches have been broadly used to study gene expression noise; however, stochastic gene expression models are usually large and time intensive to simulate. To speed up simulations, we have developed a systematic method to simplify gene expression models with fast and slow dynamics, and investigated when we can ignore the gene expression from the background genome when modelling the gene expression from plasmids. When modelling the noise in gene expression, one usually neglected aspect is the slow maturation process of fluorescent proteins, necessary for the protein to give out fluorescence after it is produced. By modelling, we show that the maturation steps can bring large changes to both the mean protein number and the noise in the model. An unstudied aspect of gene expression dynamics is the time dependent gene expression behavior in E. coli batch culture. Contrary to the usual assumption, we have found, in E. coli batch culture gene expression, that there is no steady state in terms of both the mean number of proteins and the noise. Negative feedback is thought to be able to reduce the noise in a system, and experiments have shown that negative feedback indeed suppresses the noise in gene expression, but the modelling shows that negative feedback will increase the noise. We have found that the increase of noise by feedback is due to the exclusion of extrinsic noise from the model, and that negative feedback will suppress the extrinsic noise while increasing the intrinsic noise. Living cells are crowded with macromolecules, which will, predicted by modelling, make the reaction constant time dependent. Our experimental observation has confirmed this prediction.

Keywords: Gene expression
Noise and dynamics
Advisor: McMillen, David
Functional Genomic Approaches to Study Cell Polarity Regulation by G1 Cyclins in Saccharomyces cerevisiae

In the budding yeast Saccharomyces cerevisiae, the G1-specific cyclin-dependent kinases (Cdks) Cln1-, Cln2-Cdc28 and Pcl1-, Pcl2-Pho85 are essential for ensuring that DNA replication and cell division are properly linked to cell polarity and bud morphogenesis. However, like most genes in S. cerevisiae, individual cyclin genes are not required for viability, and the phenotypes associated with deletion of any single cyclin gene tend to be subtle. My goal was to dissect the cellular roles of the G1 cyclins by systematically identifying their genetic interactions. To do this, I conducted Synthetic Genetic Array (SGA) screens using strains deleted for different combinations of cyclin genes. The results of screens with strains deleted for the G1 cyclin pairs, CLN1, CLN2, or PCL1, PCL2, confirmed a role for these cyclins in cell polarity regulation and identified novel G1 Cdk substrates, which I examined in more detail. One cell polarity regulator that showed an interesting pattern of genetic interactions with G1 cyclins was BNI1, which encodes a yeast formin protein. Overexpression of BNI1 caused an Synthetic Dosage Lethal interaction in the absence of both G1 cyclin pairs while its deletion caused synthetic lethality specifically in the absence of PCL1, PCL2. Consistent with these genetic interactions, phosphorylation of Bni1 was partially dependent on CLN1, CLN2. It has been proposed that Bni1 is regulated by intramolecular interactions. In an effort to discover how phosphorylation might affect Bni1 function, I developed assays to test for intramolecular interactions. In my experiments I found no evidence that Bni1 is regulated by intramolecular binding, as was proposed from parallels with its mouse homolog mDia1. I also found that deletion of BNI4, which encodes an adaptor protein that targets several proteins to the bud neck, results in severe growth defects in the absence of the Cdc28 cyclins Cln1 and Cln2, and overexpression of BNI4 was toxic in yeast cells lacking the Pho85 cyclins Pcl1 and Pcl2. I discovered that Bni4 was phosphorylated by Pcl1- and Pcl2-Pho85 in vitro and that phosphorylation of Bni4 was dependent on PCL1 and PCL2 in vivo. Further analysis showed that phosphorylation of Bni4 by Pcl-Pho85 is necessary for its localization to bud neck, and the bud neck structure can be disrupted by overexpressing BNI4 in pcl1pcl2 mutant cells. I propose that if Bni4 cannot be regulated by phosphorylation, it may titrate away an essential component that resides at the bud neck, thus causing catastrophic morphogenesis defects. The relationship between G1 Cdk activity and the polarity regulator Bni4 serves as a bridge to link the cell cycle machine to the regulation of cell.

Keywords: genomics
cell polarity
Advisor: Andrews, Brenda
Multidrug Resistance Protein 1 (MDR1) and Glycosphingolipids Biosynthesis: Advantages for Therapeutics

ABC drug transporter, MDR1, is a drug flippase that moves a variety of hydrophobic molecules from the inner to the outer leaflet of the plasma membrane. We have previously reported that MDR1 can function as a glycolipid flippase, being one of the mechanisms responsible for the translocation of glucosylceramide into the Golgi for neutral, but not acidic, glycosphingolipids (GSLs) synthesis. The interplay between GSLs and MDR1 could provide a whole new spectrum of innovative therapeutic options. We found that cell surface MDR1 partially co-localized with globotriaosyl ceramide (Gb3) in MDR1 transfected cells. Inhibition of GSL biosynthesis results in the loss of drug resistance and of cell surface MDR1. We speculated that an association of MDR1 and cell surface GSLs, in particular Gb3, may be functional at the cell surface, as MDR1 partitions into plasma membrane lipid rafts regulating MDR1 function. We therefore tested adamantyl Gb3 (adaGb3), a water soluble analog of Gb3, on MDR1 functions. AdaGb3 was able to inhibit MDR1-mediated rhodamine 123 drug efflux from MDR1 expressing cells, like cyclosporin A (CsA), a classical MDR1 inhibitor. AdaGb3 was also able to reverse vinblastine drug resistance in cell culture, whereas adamantyl galactosylceramide had no effect on drug resistance. The strong MDR1 reversal effects of adaGb3, as well as its favourable in vivo features make it a possible choice for inhibition of MDR1 to increase bioavailability of drugs across the intestinal epithelium (De Rosa et al., 2008). Thus, specific GSL analogs provide a new approach to MDR reversal. We have previously shown that MDR1 inhibitor CsA depletes Fabry cell lines of Gb3, the characteristic GSL accumulated in this disease, by preventing its de novo synthesis, and can also deplete Gaucher lymphoid cell lines of accumulated GlcCer (Mattocks et al., 2006). Liver and heart sections of Fabry mice treated with third generation MDR1 inhibitors showed significantly less Gb3 than liver and heart sections of untreated Fabry mice. Thus, MDR1 inhibition offers a potential alternative therapeutic approach not only for Fabry disease given the extraordinary cost of conventional enzyme replacement therapy, but also for other neutral GSL storage diseases, such as Gaucher disease.

Keywords: P-glycoprotein
Multidrug Resistance
glycosphingolipids
Fabry disease
Adamantyl Gb3
Advisor: Lingwood, Clifford A.