VictorJuiz/thesis huggingface dataset:
Novel Phases in Hetero-Epitaxial and Super-Oxygenated Thin Films of Complex Oxides

In this thesis we study structural phase transition and defect structures in complex oxide thin films induced by either heterostructuring or superoxygenation, in an effort to understand their effects on the electronic and superconducting properties. Thin films were chosen for the ability to tune the heteroepitaxial strain, as well as their large surface-to-volume ratio. We focus on two families of oxides, including the cuprate superconductors Y-Ba-Cu-O (YBCO), and the Ruddlesden-Popper iridates Sr(n+1)Ir(n)O3(n+1). We examine the effect of heteroepitaxial strain on the superconducting critical temperature (Tc) of YBa2Cu3O(7-x) (YBCO-123) thin film. Strain-induced intergrowth of CuO defect structures is seen in La(2/3)Ca(1/3)MnO3 (LCMO)/YBCO-123 bilayer films, and can account for the reduced Tc in such bilayers. Perovskite/YBCO-123/perovskite trilayers with either ferromagnetic LCMO or paramagnetic LaNiO3 (LNO) as clamping layers show similarly strong reduction of the Tc. The Tc reduction is much milder when orthorhombic PrBa2Cu3O(7-x) (PBCO) is used as clamping layers instead. These results indicate that heteroepitaxial strain, rather than long-range proximity effect, is responsible for the long length scales of Tc reduction in LCMO/YBCO-123 heterostructures. We carried out superoxygenation experiments on YBCO-123 films in order to search for novel YBCO phases. YBCO-123 films are annealed in high-pressure oxygen, in conjunction with Cu enrichment by solid-state diffusion. The annealed films show clear evidence of phase transformation to Y2Ba4Cu7O(15-x) and Y2Ba4Cu8O16, increasing with higher degree of Cu enrichment. Regions of exotic phases containing multiple CuO or Y layers are also seen in high-pressure annealed films. Our results demonstrate a novel route of synthesis towards discovering more complex YBCO phases. We also carried out superoxygenation on Sr2IrO4 (SIO) films in an attempt to metallize the iridates via hole-doping. High-pressure oxygen annealed SIO films show a progressive drop in room-temperature resistivity of up to 3 orders of magnitude, and an evolution towards metallic behavior. The post-annealed films show transformation to SrIr(1-x)O3, increasing with annealing time, pressure, and reduced film thickness. The evolution towards metallicity is attributed to phase transformation, interstitial oxygens, and Ir vacancies. The Ir vacancies in the most phase-transformed film appears to be structurally-ordered along the c-axis. Our results demonstrate a novel method for hole-doping and phase-transforming the iridates.

Keywords: Heterostructure
High Tc Superconductor
Iridate
Structural Phase Transition
Thin Film
Yttrium barium copper oxide
Advisor: Wei, John Y.T.
Characterization of Two Opposing Small RNA Pathways Required for Germline Homeostasis in Caenorhabditis elegans

Central to all small RNA pathways are the Argonaute (AGO) proteins, which interact with small RNAs to regulate gene expression in a sequence-specific manner. The characterization of AGOs across species has demonstrated that AGOs generally interact with different complements of small RNAs to perform distinct regulatory functions. In this thesis, I combined molecular biology and high-throughput sequencing to further characterize two small RNA pathways in Caenorhabditis elegans. First, I utilized the closely-related nematode species Caenorhabditis briggsae as a comparative genomics tool and determined that the CSR-1 pathway is functional in other nematode species. Next, I characterized two additional components of the CSR-1 pathway, CHP-1 and EMB-4, and implicated them in the loading of CSR-1 small RNAs and export of CSR-1 targets from the nucleus to the cytoplasm, respectively. Finally, I set out to characterize, C04F12.1, an AGO that is most closely related to CSR-1. Remarkably, I found that this AGO interacts with multiple classes of small RNAs, including the essential mir-51 family of microRNAs, which is known as the mir-100 in mammals, as well as subsets of piRNAs and CSR-1 22G-RNAs. mRNA and protein expression analyses demonstrated that C04F12.1 is broadly expressed throughout C. elegans development. Immunolocalization studies showed C04F12.1 expression predominantly in somatic tissues with dynamic nuclear localization in embryos. Genome-wide mRNA-seq data implicated C04F12.1 in silencing the expression of a large portion of germline-expressed genes. Furthermore, at elevated temperatures, C04F12.1 mutant embryos possess increased number of cells that aberrantly express germline markers. Thus, we propose a model in which C04F12.1 and its bound 22G-RNAs functions antagonistically to the CSR-1 pathway in somatic cells to silence germline gene expression and maintain somatic cell identity. Collectively, these studies have shed light on how different small RNA pathways can co-regulate mRNA targets to maintain the proper balance of gene expression.

Keywords: Argonaute
c elegans
CRISPR
microRNAs
RNAi
small RNAs
Advisor: Claycomb, Julie M
A CSR-1 guided H3K36me3 Signature Maintains Germline Gene Expression Programs In Caenorhabditis elegans

Small RNA pathways related to RNA Interference (RNAi) are prevalent in species ranging from protozoa to mammals, including humans. These pathways contribute to organismal development and cellular function and elicit their gene-regulatory impacts through diverse modes of action. The soil nematode, Caenorhabditis elegans, has emerged as a powerful system to study the endogenous activities of these pathways. In the germline, the worm has evolved an intricate network of small RNA pathways, that jointly contribute to the transmission of epigenetic information through cell divisions and across generations. This activity is necessary for the maintenance of existing germline gene expression programs, and involves the dynamic regulation of mRNA transcripts, small RNA populations, and changes to the chromatin landscape. In this thesis, I demonstrate a role for the Argonaute CSR-1 (Chromosome Segregation and RNAi defecient-1) in this process. Using genetic approaches, I demonstrate that CSR-1 licenses genes for germline expression and overcomes the silencing activity of competing small RNA pathways. I explore the mechanisms by which CSR-1 elicits its licensing activity, and identify a role for the pathway in guiding the acquisition of H3K36me3 on a genome-wide scale. Using a combination of genetic and genome-wide approaches I describe the contribution of two H3K36 methyltransferases to the CSR-1 pathway. Finally, I identify a putative self-reinforcing loop involving H3K36me3 and small RNAs that together act to reinforce an epigenetic memory of past patterns of germline gene expression. Together, these studies contribute to the understanding of how various aspects of epigenetic regulation converge to faithfully maintain existing gene expression programs in eukaryotes.

Keywords: C elegans
development
epigenetics
gene regulation
small RNA pathways
Advisor: Claycomb, Julie M
Effects of Early Embryonic Ethanol Exposure on Adult Zebrafish Social Behavior

The purpose of this thesis was two-fold: 1) to investigate preferences for various aspects of social stimuli in adult zebrafish, and 2) to investigate whether low-dose embryonic alcohol exposure affected how zebrafish responded to these various social stimuli. Control fish were exposed to different behavioral paradigms to measure responses to and preferences for various social and predator stimuli. Both male and female fish were found to prefer all-male shoals to all-female and mixed shoals, and zebrafish were able to reliably discriminate between larger shoals when ratios of 2 vs. 1 were employed. Fish avoided a moving predator image, and an elongated image of a zebrafish, which resembles a predator, and did not display a preference for yellow or red coloured fish images over control images. To test for the effects of embryonic ethanol exposure, zebrafish eggs were submerged in low concentrations of ethanol for a period of 2 hours at 24 hours post-fertilization and were tested during adulthood (4 months old onwards). Control and alcohol-exposed fish were placed in different behavioral paradigms that measured their responses to social and predator stimuli. It was found that zebrafish exposed to low doses of ethanol at 24 hours post-fertilization do not demonstrate robust differences in comparison to non-exposed control fish for any of the behaviors measured. Overall, the findings present zebrafish responses to various social stimuli, and suggest that low-dose ethanol exposure does not robustly affect social responses.

Keywords: embryonic alcohol
fetal alcohol
social behavior
zebrafish
Advisor: Gerlai, Robert
Optical Spectroscopy for Breast Cancer Risk Screening

Breast cancer (BC) has the highest mortality rate among women’s cancers worldwide, and incidence rates are rising in low- and middle-income countries (LMIC). Screening programs are well-established in most high-income countries, but there is much debate about screening frequency and the optimal screening ages. In LMIC screening infrastructure is insufficient. Optical spectroscopy (OS) can be used as a pre-screening technique to measure breast composition and predict mammographic density (MBD), a known BC risk factor. The goal of this thesis was to develop and evaluate an OS device which is portable, low cost and requires minimal operator interaction. The device was based on a research prototype used in previous studies, with two major changes: (1) a 13-laser-wavelength module replaced the broadband light source and (2) the source and detector positions were fixed within rigid holders of different sizes. The wavelengths critical for distinguishing between BC risk groups were selected using a principal components analysis of data from previous studies. Source and detector positions were chosen to match the optically-interrogated volumes of the original device via Monte Carlo simulations of photon propagation. Two versions were developed – one for women (the Cups device) and one for girls (the LEGACY device). The Cups device was evaluated in comparison with the research prototype on its ability to predict MBD. For both devices, women with high MBD could be identified from spectra with high sensitivity and specificity and correlation between mammographic percent density (MPD) and OS-predicted MPD was significant, although slightly weaker for the Cups device (r = 0.62 vs. r = 0.74). For girls, OS had been used as an objective method for distinguishing between breast development stages. Spectral analysis using only the wavelengths from the LEGACY device showed that the reduced spectral content does not affect the ability to distinguish between development stages.

Keywords: breast cancer
breast density
cancer risk
cancer screening
mammography
optical spectroscopy
Advisor: Lilge, Lothar
Planning from "Table to Dump": Analyzing the Practice of Household Food Consumption and Food Waste in Urban Indonesia

By analyzing the ways in which diverse households shop, cook, consume, and waste, this dissertation reveals the complex relationship between space, class, and social relations in the generation of household food waste in Indonesia. Several themes are explored in four empirical chapters. First, a food waste regime conceptual framework is employed to better understand unequal power relations between "modern" food provisioning infrastructures such as supermarkets, and traditional food provisioning infrastructures, specifically in relation to space restriction and predatory pricing. Secondly, the food waste regime framework is also applied to examine the role of class and privilege in determining an individual's ability to define "what is food and what is waste" within the boundaries of the household. Thirdly, the application of the conceptual framework of "distancing" articulates the role of urbanization in the spatial and mental distancing of both the food supply chain and waste management infrastructure. Finally, from a statistical perspective, the dissertation examines whether income level and where people choose to shop (for example, the type of retail) impact the amount of household food waste generated in Indonesia. Using practice theory, planners are encouraged to take a closer look at different types of retail formats to understand how space may impact consumption. This study draws upon a qualitative study of 21 upper (n=7), middle (n=7) and lower (n=7) income households in Bogor, 12 key informant interviews with government officials, traditional food vendors, supermarket managers, and a waste collector, as well as the result of a quantitative study on 323 households. To conclude, this dissertation argues that there is a need to offer infrastructural support that can protect traditional food retail and promote more sustainable food waste management. Furthermore, considerations for social and environmental justice are key in the search for a systemic and dignified solution to the issue of food waste in Indonesia.

Keywords: food consumption
food waste
Indonesia
infrastructure
planning
practice theory
Advisor: Maclaren, Virginia
Identification of Biologically Relevant Binding Targets of SH3 Domains Using a Compensatory Mutation Approach

Protein-protein interactions are crucial for cellular function. Many protein-protein interactions are mediated by peptide recognition modules (PRMs), small domains in proteins that recognize and interact with short peptide sequences in target proteins. In many systems, the interactions between PRMs and target proteins have been investigated using high-throughput methods. These studies have revealed protein-protein interaction networks where single PRMs apparently interact with dozens of different proteins. Some of these interactions may be false positives, may never occur in vivo, or may not be involved in any biological function. Thus, a key challenge arising from these studies is to identity protein-protein interactions that are “biologically relevant”. In this thesis, I define a biologically relevant interaction as one where specific disruption of the interaction can be definitively shown to cause a detectable phenotype under some genetic background or environmental condition. The goal of my work has been to design and test a generalizable approach, which I call “the compensatory mutation approach”, for determining whether particular protein-protein interactions are biologically relevant. To develop my approach, I studied the function of SH3 domains in budding yeast, Saccharomyces cerevisiae, as a model system. In particular, I focused on the SH3 domains found in two yeast proteins, Abp1p and Nbp2p. Using the compensatory mutation approach, I identified biologically relevant binding targets for both of these domains. Importantly, I showed that the biologically relevant binding targets may change depending on the phenotype tested and the assay conditions. I also demonstrated that the pathway involving Abp1p can be re-wired in such a way as to eliminate the requirement for the Abp1p SH3 domain. This study has provided the first unequivocal identification of biologically relevant targets for the Nbp2p and Abp1p SH3 domains, and established that the compensatory mutation approach can supply unique insights into the functioning of biological pathways.

Keywords: compensatory mutation approach
protein-protein interaction
SH3
Advisor: Davidson, Alan R
Work Ability and Return to Work Following a Traffic Injury

Background: Traffic injuries are a common source of work absenteeism. However, little is known about the factors associated with return to work following traffic injuries. One factor that may be a strong predictor of return to work is work ability. Objectives: 1) To determine whether modified work is a mediator of the association between work ability and return to work in a cohort of individuals injured in a traffic collision (Manuscript 3). 2) To identify factors associated with work ability by conducting a scoping review of the literature (Manuscript 1). 3) To develop a measurement model of work ability (Manuscript 2). Methods: The scoping review surveyed the literature for common measures of work ability and used the International Classification of Functioning, Disability and Heath framework to map factors associated with work ability. This informed the development of a reflective measurement model of work ability using confirmatory factor analysis. The measurement model was then used to examine the direct and indirect effect (through modified work) of work ability on return to work using a structural equation model. All analyses were conducted in a population-based incidence cohort of traffic injuries from Saskatchewan, Canada. Eligible participants for this thesis included those with acute soft tissue injuries. Work ability was measured at baseline and direct and indirect effects were studied longitudinally by examining modified work at six weeks and return to work at three months. Results: The second-order factor measurement model included four first-order factors (physical, psychological, cognitive functions, activities and participation) and 17 measured variables. The structural equation modeling suggests that work ability and modified work were positively and independently associated with return to work. However, work ability was not associated with modified work. Conclusion: This thesis supports the multidimensionality of work ability and recognizes its direct association with returning to work. This research also highlights the importance of modified work to the return to work process following a traffic injury.

Advisor: Côté, Pierre
Characterization of Tie2 signalling during acute inflammation

The inflammatory response is essential for the eradication of lipopolysaccharide (LPS) presenting microbial invaders. However, resolution is also important to prevent detrimental vascular inflammation to the host. Endothelial cells play active roles in inflammation by detecting LPS using Toll-Like Receptor 4 (TLR4), leading to the activation of Nf-κB, but also participate in the resolution of inflammation, in part, through the actions of the receptor tyrosine kinase, Tie2. The process by which Tie2 can attenuate LPS-TLR4 driven inflammation is poorly understood. The work herein centers upon the characterization of Tie2 signalling during acute inflammation. The effects of Tie2 activation using the Tie2 agonist, Vasculotide (VT), was monitored in an animal model of endotoxin induced inflammation. Activation of Tie2 resulted in reductions in vascular permeability, levels of circulating inflammatory cytokines, and the number of leukocytes at the site of inflammation following LPS stimulation, confirming the anti-inflammatory effect of Tie2 signalling following LPS-TLR4 driven acute inflammation. To investigate the crosstalk between Tie2 and TLR4, Nf-κB activation was monitored in cells expressing Tie2 mutants harboring tyrosine (Y) to phenylalanine mutations in the carboxy-terminal tyrosine residues essential for downstream Tie2 signalling. Tie2 signalling reduced LPS induced Nf-κB activation in a Y1100 and Erk1/2 dependent manner. Tie2 signalling decreased the expression of the TLR4 signalling proteins, TRAF6 and IRAK1 and preserved the expression of the Nf-κB inhibitor, IκBα, though Y1100 initiated Erk1/2 signalling. The ability of Tie2 to increase the expression of miRNA-146b-5p was investigated and found to be dependent on functioning of all three carboxy-terminal tyrosine residues. Our results show that Y1100 initiated Erk1/2 signalling is essential for the anti-inflammatory effect of Tie2 on TLR4 driven Nf-κB activation. Characterization of the role of Tie2 signalling during an inflammatory cascade will further our understanding of the biology of Tie2 and ultimately contribute to our understanding of the regulation of vascular inflammation.

Advisor: McGlade, Catherine J
Transnational Latina Feminism in Toronto, Canada, 1970s–2000s: Treading the New Avenues

Latin American women have a long history of anti-imperialist and anti-capitalist political engagement, expanding into feminist praxis with diverse women’s movements across Latin America. Following connections with the Chicana cannon and establishing connections with other racialized grassroots groups in Canada, a particular Latina feminist subjectivity emerged that complicates Canadian feminism and challenges dominant narratives of Latin American political activities. Canadian feminist historiographies regularly engage in processes of erasure that inscribes Whiteness and imperialism into the Canadian landscape. In this context, Latin American women’s agency, experience, and lives have tended to disappear—along with other racialized women—from Canadian consciousness and literature, relegating them to the perpetual and exclusive role of victims. In this dissertation, four historical junctures have been selected that illustrate the transnational praxis of Latin American women’s feminist subjectivities in the city of Toronto, Ontario, Canada. These key moments showcase complex political debates, including the political crisis in Latin America, the imposition of neo-liberal policies, political repression, and exile. Diasporic Latin American women from the 1970s to the early 2000s developed organizations that responded to the political exigencies of the times, maintaining transnational connections with women’s and feminist movements in Latin America while also creating new spaces in Canada, ultimately evolving a unique diasporic Latina feminist subjectivity. These junctures are: (1) the solidarity movement of the 1970s to the 1990s, focusing on two women’s organizations; (2) the formation of the Latin American Coalition to End Violence against Women and Children (LACEV) in the 1990s; (3) the organization of the First Latin American and Caribbean Women’s Encounter in 1995; and (4) the foundation of MUJER in 2003. These four examples are neither linear nor lacking in controversy. This study is based on a mixed methodology that includes interviews with leading activists, document analysis, and personal experience. Throughout their historical journeys, Latin American women contributed not only to the processes of democratization in their countries of origin but also to Toronto’s feminist political milieu, providing a vital contribution and translating into invaluable organizations that continue to support Latin American women’s agencies and political praxis.

Keywords: community agencies
exiles
feminist
Latin American
Toronto
women
Advisor: Bakan, Abigail