VictorJuiz/thesis huggingface dataset:
Effect of Folate Dose and Form during Pregnancy on Early- and Later-life Phenotype of the Wistar Rat Mother and Her Female Offspring

High gestational folic acid (FA, synthetic folate) programs long-term metabolic consequences in the offspring. The hypothesis of this research is that the dose and form of folate consumed during pregnancy determines the post-birth and long-term phenotype of Wistar rat mothers and female offspring through effects on central hypothalamic and peripheral energy regulatory mechanisms. Three studies were conducted. In Study 1, pregnant Wistar rat were fed an AIN-93G diet with FA at 0X, 1X (control), 2.5X, 5X, or 10X recommended levels then switched to a control diet during lactation and for 1-week post-weaning when dams were terminated to address early postpartum effects. In Study 23, pregnant dams were fed either 1X- or 5X-FA or equimolar doses of 5-methyltetrahydrofolic acid (MTHF). Mothers and female offspring were maintained on a high-fat (45% lard) diet for 19 weeks. In Study 1, FA below (0X) or above (5X, 10X) recommended intakes delayed the re-set of body weight and metabolism in dams after birth. In Study 2, both 5X doses delayed post-birth maternal weight-loss but 5X-MTHF compared to 5X-FA dams had greater post-weaning weight-gain and food intake. These effects associated with altered expression of energy regulatory genes in the hypothalamus and peripheral hormones. In Study 3, 5X-MTHF compared to 5X-FA diets increased post-weaning weight-gain and food intake in the female offspring and associated with modified central and peripheral mechanisms. Alterations in folate-mediated 1-carbon metabolism were consistently observed. In conclusion, both folate dose and form during pregnancy alter the early- and later-life phenotype of the Wistar rat mother and her female offspring via central hypothalamic and peripheral energy regulatory mechanisms. Further consideration of the amounts and forms of folates added to the food supply and pre-natal supplements is needed.

Keywords: 1 carbon metabolism
Folate
Folic acid
in utero programming
Maternal programming
Pregnancy
Advisor: Anderson, G. Harvey
Mitochondrial Dysfunction in Bipolar Disorder with a Family History of Mitochondrial Disease: From Family Genetics to Patient-derived Induced Pluripotent Stem Cell-based Neuronal Models

Bipolar disorder (BD) is a complex mood disorder with high heterogeneity and unclear pathophysiology. Mitochondrial dysfunction has been repeatedly observed in BD; however, our understanding of mitochondrial dysfunction remains incomplete due to the lack of patient stratification, nuclear and mitochondrial genomics, and patient-derived neuronal models. The objective of this thesis was to investigate mitochondrial genetics and function in BD with or without a family history of mitochondrial disease. To achieve this, we (1) identified two families, each with at least one surviving member with BD and two deceased offspring with mitochondrial disease and BD patients without family history of mitochondrial disease; (2) performed nuclear and mitochondrial genome sequencing to evaluate family genetics and; (3) developed patient-derived induced pluripotent stem cell- (iPSC-) based neuronal models to uncover mitochondrial signatures specific to BD with a family history of mitochondrial disease. Nuclear and mitochondrial genome sequencing uncovered two novel variants in two genes, NUBPL and COMT, shared amongst BD across two unrelated families. While these variants require functional validation, we showed that bi-genomic sequencing could detect novel variants. Next, we generated patient-derived iPSCs and neural progenitor cells (NPCs). Grouping the family cases by the NUBPL and COMT variants, we identified that BD with a family history of mitochondrial disease presented lower maximal respiration in the iPSCs, higher proton leak and lower total ATP levels in NPCs compared to relatives. Furthermore, BD with a family history of mitochondrial disease presented lower glycolytic markers in the iPSCs than BD without a family history of mitochondrial disease. Our study demonstrates the importance of stratifying the heterogeneous BD patients into mitochondrial-based subgroups to unveil unique signatures of mitochondrial dysfunction. While single-cell models like iPSCs and NPCs offer insights into disease pathophysiology, there is a need to develop a disease model that recapitulates the complexity of the human brain. Therefore, we developed cerebral organoids (COs) from iPSCs derived from human peripheral blood mononuclear cells (PBMCs) and demonstrated preserved mitochondrial genetics and function across PBMCs to iPSCs to COs for the first time. These COs may serve as models to further investigate the role of mitochondrial dysfunction in BD.

Keywords: Bipolar Disorder
Cerebral Organoids
Genetics
Induced Pluripotent Stem Cells
Mitochondria
Psychiatry
Advisor: Andreazza, Ana C
Urban Neoliberalism and External Partnerships in the City of Toronto's Tower Renewal Program

In 2008, the City of Toronto ('the City') adopted Tower Renewal as a municipal policy and program with the stated objective of helping to revitalize Toronto's postwar high-rise apartment buildings and surrounding neighbourhoods. These apartments were built in the post-World War II period and are predominantly privately owned. This dissertation examines the external partnerships that are being employed by the City for Tower Renewal policy development in municipal offices, and implementation in privately-owned postwar apartment buildings. These external partnerships involve planning professionals from private sector firms, non-profit sector organizations, community-based organizations, and private postwar apartment owners. The overarching argument presented in this dissertation is that Tower Renewal demonstrates the complexities and challenges of local public policy development and delivery in the governance context of urban neoliberalism. Neoliberalism is reflected in four main ways in Tower Renewal that include: (1) discourse and practice of fiscal austerity in municipal offices; (2) popularity of partnership-based policy mechanisms; (3) offloading public policy responsibilities to non-governmental actors; and, (4) the constraints and opportunities that diverse urban actors are confronted with in this new era of partnership-based governance, and within urban neoliberalism more broadly. Although external partnerships have been essential for Tower Renewal policy development and delivery since 2008, my research reveals that the participation of external actors is presently unsustainable and ineffective due to the lack of adequate public-sector financial support and incentives. Theoretically, Tower Renewal also challenges the notion of urban actors as simply passive victims of neoliberalism. Throughout this dissertation, documented are instances where diverse urban actors are strategically engaging in neoliberal policy partnerships with some success in incrementally implementing their progressive agendas. It is through establishing multi-sector policy partnerships, which strive towards more socially and environmentally progressive ends, that these urban actors are challenging neoliberalism from within. In the concluding chapter, I suggest ways to better support the involvement of non-profit and private sector actors in Tower Renewal’s external partnerships. I also recommend an alternative, more traditional approach, to the City’s current emphasis on neoliberal policy partnerships.

Keywords: community-based organizations
local governments
neoliberal governance
public policy delivery
public-private partnerships
urban revitalization
Advisor: Bunce, Susannah
Impression Formation in the Digital World

The need for impression management and identity signaling is one of the core motives behind consumer behaviors (Baumeister Leary, 1995; Gal, 2015). Researchers have studied how consumers disclose their personal attributes and consumption attitudes extensively (Han et al., 2010; Kurt et al., 2011). However, little is known about how observers respond to these social signals. In other words, the effectiveness of many impression management behaviors remains unknown. Although new technologies like social media have revolutionized people’s social lives, academic research knows little about how consumers view others in the digital age. The present dissertation examines how perceivers form impressions on presenters when different types of consumer attributes and attitudes are observed. Essay 1 focuses on public impressions of a person’s online inconsistent disclosure about themselves (e.g., a book lover who goes to night clubs frequently). I reveal that people can form not only negative impressions of the person, rooted in greater perceived inauthenticity, but also positive reactions, indicating greater perceived versatility. The moderating role of relationship closeness, perceiver traits, and implicit theories were tested. Essay 2 demonstrates that people who express valenced consumer attitudes (i.e., liking and/or disliking brands and products) are viewed more favorably than people who express neutral consumer attitudes (i.e., neither liking nor disliking brands and products). The effect is driven by dehumanization of consumers who have neutral attitudes. Within valenced consumer attitudes, positive attitudes are found to bring more favorable impression than negative attitudes. Empirical evidence was provided in a series of lab experiments and an archival dataset. The current research contributes to the impression formation literature by showing how inconsistent personal attributes influence impression favorability. It validates the conception of connectionist models that not only the content of attributes, but also the structure and associations among them, determine social impression (Kunda Thagard, 1996). The research also offers insights into consumer attitude literature (Argyriou Melewar, 2011) by demonstrating a subtle form of dehumanization induced by neutral attitudes. The literature on impression formation was reviewed, along with discussions on how online social media provides an avenue ripe for future research.

Advisor: Lee, Spike WS
Leonardelli, Geoffrey J
Multiscale Modelling of Hydrochlorination Reactions for Solar Grade Silicon Production

The rapid growth in silicon photovoltaics deployment has led to increased research focus on the energy and capital intensive refining of solar grade silicon. The most commonly implemented first step in refining of solar grade silicon involves converting metallurgical grade silicon to gaseous trichlorosilane (TCS). In order to further investigate this reactive process, the interaction of H2, HCl and relevant chlorosilanes with the Si(100)-c(4x2) surface and catalytic Cu3Si surface was investigated using atomic scale density functional theory (DFT). All molecules underwent dissociative chemisorption with HCl and SiCl2 possessing the strongest binding energies. An elementary reaction network was derived for each surface, with 27 reactions for Si (100) and 20 reactions for Cu3Si, exploring formation of all chlorosilane intermediates species from two to four atoms, five product gas species as well as surface diffusion. The activation barriers and reaction rate constants for each of these reactions were also determined. Activation barriers were significantly lower for the Cu3Si. These values were then fed into meso-scale kinetic Monte Carlo (KMC) simulations, including the effect of lateral interactions, over a temperature of 900 - 1200 K. The production of TCS on Cu3Si was at least four orders of magnitude higher than on the Si (100). The formation of TCS on Si (100) was found to have four possible routes, involving SiCl2*, SiHCl* or SiCl3* as key intermediates. The formation of SiCl* from a solid surface Si atom or the formation of SiHCl2 from SiHCl* was found to be the rate determining step (RDS) depending on pathway. The formation of TCS on Cu3Si had only one active pathway, with SiCl3* as a key intermediate and one step formation of SiCl2* from surface Si as RDS. The SiCl* adsorbate strongly disliked presence of H* or Cl* and this inactivated several predicted reactions. TCS production had higher selectivity on Cu3Si for low to mid temperatures and peaked in production rate and selectivity at 950 K. Effective activation energies were obtained for use in macroscale modeling. This work gives insight into reaction mechanisms for hydrochlorination surfaces and kinetic parameters which can be used in process optimization and development.

Advisor: Singh, Chandra V
A Study of the Influence of Global University Rankings on Institutional Strategies, Decision-Making, and Policy Choice: The Case of Four Canadian Research Universities

Since 2003, global rankings have continued to impact higher education at both the systemic and institutional levels. Emerging in an unprecedented period of intensified global economic competition in which the competitive advantage of individual countries runs on knowledge and innovation, these novel rankings have risen rapidly to the forefront of higher education policies in many countries, leading governments to institute new jurisdictional priorities for universities. In implementing rankings, universities have adopted practices and processes that sometimes have had deleterious effects for both sound educational administration and accountability (Hazelkorn, 2011). This multiple-case study examined how the senior leaders of four Canadian research universities formulate responses to their institutions standing in global university rankings.Theoretically, the topic was intellectualized through the lens of two organizational theory perspectives: institutional theory and resource dependence theory. This integrated approach led the researcher to theorize that due to the intensification of reputational advantage mediated by rankings, the four institutions under analysis would change practices, processes, and administrative structures to improve and/or sustain their positions in global rankings. Empirically, the study used a multi-method approach. Thus, data were derived from three qualitative research strategies: (i) document analysis, (ii) 15 semi-structured interviews with senior administrators of participating universities, (iii) website analysis. This provided triangulation and allowed cross-validation of findings. Data analysis revealed three primary areas wherein rankings exert direct influence: rankings-related capacity, international collaborations, and branding. Rankings additionally influence other interrelated areas: legitimacy seeking, strategic positioning, and internal accountability. Additionally, while the analytical framework has shown to have explanatory power, the study found that the leading drivers of these behaviours are isomorphism and resource dependence, with mimetic isomorphism in pursuit of legitimacy trumping rational considerations of resources. Moreover, interviews showed that the source of such nonrational conduct stems from assumptions which predispose senior administrators to overstate the importance of adopting procedures oriented to rankings. The study identifies implications of these sorts of institutional behaviours for the administrative cost of university education and diversity. Implications for policy and practice are also presented that audiences, such as higher education leaders, university administrators, and future researchers may find useful.

Keywords: accountability
Canada
global competitiveness
higher education
international university rankings
organizational theory
Advisor: Wheelahan, Leesa L
Seminars as Communities of Practice: The Structural Analysis of Four Graduate-level Seminars and the Spoken Participation Experiences of International Students in a Canadian University

Canadian universities and colleges are increasingly characterized by diversity. In academia, the number of individuals using English as an additional language (EAL) exceeds the number of scholars and students speaking English as their native language. However, previous studies have explored academic English among English monolingual speakers and many of these studies have focused on the written aspect while spoken genres such as seminars remain underexplored.This research is an embedded multiple case study that focuses on exploring the spoken participation experiences of EAL international students in four graduate-level seminars in a Canadian university. The research questions are: 1) How do four graduate-level seminar courses in Education in an English-language university differ in terms of their schematic structure, implementation, and instructor expectations for participation?; and 2) How do the EAL international student participants experience spoken participation in four graduate-level seminar courses? Each seminar course was conceptualized as a case and participants were embedded subunits of analysis. Data were collected using classroom observations, interviews, as well as physical artifacts and analyzed using genre and thematic analysis. Drawing on genre theory, community of practice, and landscape of practice, this study discussed how each instructor’s particular style of teaching and perception of their role in the classroom are reflected in the structure of each seminar course and closely associated with instructors’ different expectations for participation. These differences contributed to the confusion that student participants experienced. In addition, the international students encountered difficulties related not only to language, but challenges stemming from diverse understandings of spoken participation and classroom context-specific challenges. Thus, they perceived themselves as novice members of the community engaged in participation on the periphery as opposed to some of their classmates who were seen as more expert members. As this study highlights the varied structure of graduate seminars as well as the range of demands and participation expectations in seminars as elements that can contribute to spoken participation difficulties of international students, there are a number of implications that pertain to graduate program preparation as well as the professional development of professors in graduate programs that include international students.

Advisor: Gagné, Antoinette
Development of Copper-catalyzed Processes towards the Synthesis of Tetrahydroquinolines, Benzoxazinones and Fused Triazoles

The Lautens group has a long-standing interest in the application of transition metal catalyzed reactions in developing strategies towards synthesizing biologically relevant heterocycles. This thesis focuses on the development of various copper-catalyzed transformations that enable the efficient syntheses of tetrahydroquinoline, benzoxazinone, and fused trisubstitued triazole heterocycles. Chapter 1 describes a process to synthesize borylated tetrahydroquinoline scaffolds using a copper-catalyzed borylation of Michael acceptors in tandem with a Mannich-type cyclization. The use of Michael acceptors as π-systems in copper-catalyzed borylation reactions is well known, however their application to generate heterocycles in domino processes remains largely underdeveloped. This strategy is feasible with a broad range of Michael acceptors, and can be leveraged to generate versatile borylated tetrahydroquinoline scaffolds bearing three contiguous stereocenters in a diastereo- and enantioselective fashion. Chapter 2 details the development of a multi-step strategy enabling the synthesis of benzoxazinone scaffolds. The developed method relies on an initial selective copper-catalyzed borylation across an α,β-unsaturated ester or amide, subsequent C−B bond oxidation to generate the reactive alcohol intermediate, and a cyclization to generate the desired heterocyclic product. The application of chiral ligands in this strategy was also demonstrated, generating the benzoxazinone moiety in an enantioselective fashion. Chapter 3 focuses on the utilization of the copper-catalyzed azide alkyne cycloaddition reaction in the synthesis of trisubstituted 1,2,3-triazoles. The mechanism of the copper-catalyzed azide alkyne cycloaddition involves the generation for a nucleophilic copper-triazolide intermediate. Typically, this intermediate undergoes protodemetallation to generate 1,4-disubstituted 1,2,3-triazole compounds. However, the tethering of carbamoyl chloride functional group enables an intramolecular cyclization generating novel, fully-substituted, fused 5-acyl 1,2,3-triazoles.

Keywords: Borylation
Catalysis
Copper
CuAAC
Heterocycle
Synthesis
Advisor: Lautens, Mark
Program Domains of Trauma-Informed Practice Associated with Client Perception of Care and Staff Perceived Organizational Support: A Study of Women’s Substance Use Programs Utilizing Qualitative Comparative Analysis

Background: Trauma-informed practice (TIP) is a strength-based service delivery approach that acknowledges the widespread prevalence and impact of trauma in the lives of both the people seeking services as well as amongst its’ workforce (Harris Fallot, 2001; SAMHSA, 2014). As programs and organizations implement a TIP approach to service delivery, examining the degree to which an organization is able to integrate TIP principles into their practices and operations and how it relates to client and staff perception of care can be helpful for program evaluation. Purpose Objectives: Guided by a Knowledge Based View (KBV) of the firm (Grant, 1997; 2002; 1991) and Resource Based Theory (RBT) (Barney, 1991), this study sought to examine combinations of program domains and the degree to which they are trauma-informed that are associated with client perception of care and staff perceived organizational support. Methods: A case study design involving nine women’s substance use agencies across the province of Ontario, Canada was employed to study TIP organizational capability in six program domains. To facilitate the study of combinations of organizational capability domains that are associated with the outcomes, Qualitative Comparative Analysis (QCA) was used as the main analytic approach. Findings: QCA results indicate, that the degree to which program domains are trauma-informed may not be related to staff perceived organizational support and client perception of care outcomes as anticipated. It is possible that organizational capability in TIP has more distal and perhaps little connection to the outcomes as measured by the SPOS and OPOC. Conclusions: Although the CCTIC has utility to inform program planning and implementation for trauma-informed services, it may be challenged as a tool to evaluate the extent to which program domains are associated with client perception of care and staff perceived support. Future studies should look at replicating the CCTIC as a more refined and calibrated measure of TIP that can be readily used to evaluate TIP as it relates to provider and client experiences of care to inform policy and program evaluation.

Keywords: Client Perception
Culture
Organizational Capability
Staff Experience
Trauma-informed
Advisor: Rush, Brian
Barnsley, Jan