VictorJuiz/thesis huggingface dataset:
TRAF1 in Human Health and Disease

TRAF1 is a signaling adaptor known for its role in tumour necrosis factor receptor (TNFR)-induced cell survival. This thesis explores the role of TRAF1 in human health and several disease states, including autoimmunity, infectious disease and cancer. Genome wide association studies identified an association between single nucleotide polymorphisms (SNPs) in the TRAF1 gene with increased incidence of rheumatoid arthritis (RA) and other autoimmune diseases. I provide a compelling explanation for how this SNP could contribute to the increased incidence and severity of RA and other inflammatory diseases by presenting evidence that healthy donors with the RA-associated SNP express less TRAF1 protein but higher levels of inflammatory cytokines due to an unexpected role for TRAF1 in negatively-regulating TLR signaling. In the context of infectious disease, it had been shown that the loss of TRAF1 from chronically stimulated CD8 T cells results in desensitization of the 4-1BB signaling pathway, thereby contributing to T cell exhaustion during chronic infection. Previous results showed that IL-7 can restore TRAF1 expression in virus specific CD8 T cells in mice, rendering them sensitive to anti-4-1BB agonist therapy. I show that IL-7 therapy in antiretroviral therapy treated patients induces sustained changes in the number and phenotype of HIV-specific T cells, including increased levels of phospho-ribosomal protein S6 and increased frequency of TRAF1+ cells. TNFR family members such as CD40 play important roles in driving NF-B activation in B cell related cancers, including chronic lymphocytic leukemia (CLL). Here I present evidence that the protein kinase C related kinase, PKN1, is required to protect the pro-survival signaling adaptor TRAF1 from degradation during constitutive CD40 signaling. Accordingly, treatment of patient CLL cells with a PKN1 inhibitor lowered TRAF1 and other survival molecules and resulted in increased cell death. These findings provide proof of concept for PKN1 as a novel target for killing CLL cells. Altogether, these studies have advanced our understanding of the impact of TRAF1 in human disease as an important molecule that can limit inflammation and contribute to control of chronic viral infection. My findings also identify TRAF1 as a potential biomarker and may inform the development of a novel therapy for human B cell malignancies.

Keywords: chronic lymphocytic leukemia
HIV
human immunology
rheumatoid arthritis
TNFR
TRAF1
Advisor: Watts, Tania H
Symphonic Victimae Paschali Laudes

Symphonic Victimae Paschali Laudes is a work for full orchestra based on the Gregorian chant Victimae Paschali Laudes. The composition is approximately 14’40’’ long and fuses elements of early music (Gregorian chant, organum) and contemporary music (use of extended instrumental techniques, coloristic textures). After a serene Introduction (mm. 1-28) bringing the first notes of the Gregorian chant over harmonics on the strings, the first phrase of the Gregorian chant is presented (mm. 29-43), followed by a harmonic transition and a hectic bridge (mm. 44-75) leading to the presentation of the second phrase of the Gregorian chant (mm. 76-116). Then, sections using ideas from the beginning as well as new ideas take place (mm. 117-330), starting with melodic material from the bridge combined with “intriguing” chords fading in and out. The two first phrases of the Gregorian chant reappear with variations and over different orchestral textures. New melodic material also ensues, and the “intriguing” chords reappear bringing tension. The tension is resolved with the reappearance of the Gregorian chant (mm. 331-end), which now is stated entirely—not only the two first phrases—into a maestoso character, with parallel fifths over pedal notes within a varied orchestration. The final measures of the work (375-end) are based on the words “amen” and “alleluia”. The composition ends in a grandiose but serene manner.

Keywords: orchestra
symphonic
Victimae Paschali Laudes
Advisor: Palej, Norbert
A Posthumanist Study of Health and the Food System: Vegetal Politics in Toronto Urban Gardens in the Anthropocene

This critical qualitative study explores the ontological split between humans and nature, identified by scholars including Val Plumwood and Donna Haraway, and considers human health and the food system in the Anthropocene. I draw on posthumanist theory to investigate what happens to understandings of food systems and health if the ontological dualism in Euro-Western thought that separates humans from nature is challenged, or even undone. What is a posthumanist understanding of health in the food system? What is a posthumanist approach to food systems and health in the context of the city, during this time of rapid urbanization, environmental destruction and climate change? I engaged with gardeners who grow food in the City of Toronto and their plants. Garden visits and interviews were conducted with 23 gardeners about their growing practices, plants and conceptions of health and wellbeing. To place these growers in context I conducted key informant interviews on urban agriculture; consulted grey literature including municipal reports, seed catalogues and archival material; and implemented a survey (N=103) with a wider group of growers. Participant observation involved working in community gardens during the growing season of 2018 as part of a multispecies ethnography where plants were considered as participants of equal importance to humans. Part One explores the theoretical underpinnings and the methodology I developed to identify plant agency in gardens. Part Two presents the empirical work that investigates health, vegetal politics and plant agency in Toronto. Part Three lays out the contributions of the thesis. The theoretical contribution is a posthumanist understanding of health in the food system. The methodological contribution is a three-step approach to accounting for plant agency. The substantive contribution is about plant agency. I argue that plants are actors in the redevelopment of the Toronto’s Regent Park and that plants co-produce food sovereignty and support the ecological determinants of health. These findings contribute to an understanding of what is being called ‘vegetal politics’ and expand on definitions of health as related to food production and consumption.

Keywords: gardens
human-nature relationship
non-human agency
posthumanism
urban agriculture
Advisor: Poland, Blake
Stochastic Optimization of Covered Call Strategies

We present scenario-based stochastic optimization models to construct covered call strategies. Unlike existing studies which have tested heuristics for forming covered calls and have largely been descriptive in nature, our models prescribe the construction of optimal covered call strategies to produce either risk-return efficient or expected utility-maximized strategies. We present models where we define the sample expected return, sample risk, and sample expected utility based on the return of a covered call strategy in numerous simulated scenarios. All models we propose feature only linear constraints and either linear, quadratic, or convex objective functions. With some innovation all models we present are computationally tractable using over fifty assets and several hundred call options. In contrast to existing studies which typically focus on covered calls formed on a single asset by fully overwriting with an at-the-money or slightly out-of-the-money option, we explore covered call strategies of a more general form which include: multiple underlying assets, partial overwriting, and overwriting by simultaneously selling call options of different strike prices and maturity dates. We find that optimized covered call strategies exploit this generalized form. Popular heuristics in the literature and in practice which select strike prices based on a fixed level of moneyness or probability of exercise fail to consider the option market prices as part of the selection process. The call option market prices are critical inputs to our models. We show that expected return-maximized covered call strategies are directly linked to call risk premiums, one component of which are the option market prices. Covered calls are traditionally formed as an overlay on existing asset positions. Our analysis suggests that covered calls formed in two steps by first optimizing underlying equity positions then selecting call overwriting weights are not risk-return optimal in general. We propose optimization frameworks which construct covered call portfolios by simultaneously selecting underlying asset positions and call options to sell. We detail the implementation and testing of various models, and draw insight into the structure of optimized covered call strategies.

Keywords: Asset management
Covered calls
Operations research
Portfolio optimization
Stochastic programming
Advisor: Kwon, Roy H
‘Seamless’ Transition to Citizenship? International Student Graduates, Race, and Structural Inequities in Canada’s (Im)migration-Labour Market

Abstract Canada, like other economically-advanced nations, has gradually been implementing internationalization strategies to respond to the pressures brought on by globalization. The federal government, in 2014, launched an International Education Strategy, a university/college-led scheme to increase the number of international students to Canada. After completing Canadian postsecondary studies, they may transition to the labour market and then to permanent residence (reputedly ‘seamlessly’) via one of Canada’s economic immigration programs. This research critically analyzes the trajectory of international student graduates originating from the Caribbean and South/Southeast Asia as they navigate the labour market-immigration transition. The qualitative study is framed by theoretical perspectives drawn from anti-racist/postcolonial prisms, critique of neoliberalism, and conceptualizations of social capital and social closure to understand and interpret the lived experiences of 18 international student graduates of Ontario colleges and universities. My analysis as well as five key informants supported the conclusion that Black Caribbean and South/South Asian student migrants with Canadian credentials do not experience a seamless transition from their post-graduation phase to Canadian permanent residence (PR). The findings reveal ‘hidden’ problems behind the apparent neutrality of Canada’s points system, and protracted wait times associated with Canada’s economic immigration programs as well as the emotional and psychological pain experienced by student migrants. It also demonstrates how federal policies such as the National Occupational Classification (NOC) codes and the Labour Market Impact Assessment (LMIA) influence the transition of international student graduates. These racialized participants ‘whiten’ their resumés, and call upon various types of consultants and actors in their racial and interracial networks to circumnavigate structural inequities in obtaining employment. Not all the consultants are fully informed about immigration policy and omit crucial information or advise strategies that ‘off-ramp’ those applying for PR. Further, there are differences between applicants in their access to interracial networks necessary for obtaining employment. Finally, my study indicates that the labour market integration of Black Caribbeans and South/Southeast Asians in Canada is influenced by the complexities of gender, race, and racialization.

Keywords: Gender
Immigration
International Student Graduates
Labour Market (Work)
National Occupational Classification Codes
Race
Advisor: Muzzin, Linda J.
Does Democracy Matter? Political Change and National Identification in South Korea and Beyond

What is the relationship between political system type and preferences for national membership and belonging? Existing research suggests that preferences and institutions align. Cross-national work indicates that citizens in countries with consolidated democratic institutions have national identities that are more open and inclusive, whereas those in countries with weak democratic or authoritarian institutions tend to have more closed and exclusive national identities. But what about citizens in new(er) democracies? Do identities forged under autocratic regimes change, or are they resilient over time? Using pooled cross-sectional data on South Korean national identity between 2003 and 2015, this thesis considers whether people who were socialized under authoritarian political conditions have national identities different from those who came of age under democracy. Further, using newly collected survey and interview data, this thesis also leverages a natural experiment in institutional change to isolate the effects of both “growing up autocratic” and exposure to democratic institutions by comparing responses from native South Koreans with that of resettled North Korean migrants. The research presented here confirms the association between system type and national identity; democrats have more pluralistic and voluntarist conceptions of national membership and autocrats hold higher barriers to belonging and have more ascriptive national identities. The thesis further indicates the type of political system in which citizens are socialized determines, at least in part, their national identity. Overall, the research findings presented in this thesis make three contributions. First, it adds further evidence to existing bodies of literature which hold that institutions and individual preferences tend to align. Second, it also confirms findings from existing literature on political socialization, showing that formative years’ experiences generate attitudes that endure over the life-cycle. Third, it adds new insight and understanding of changes in South Korean national identity across generations.

Keywords: Migration
National identity
Natural Experiment
Public Opinion
Socialization
South Korea
Advisor: Wong, Joseph
"The Sky’s the Limit": On the Impossible Promise of E-learning in the Toronto District School Board

Under the banner “The Sky’s the Limit,” electronically delivered instruction (e-learning) in the Toronto District School Board (TDSB) emerged as an approach that promised expanded opportunities for students to prepare for a competitive, globalized, and networked economy. In contrast, this year-long ethnographic study on e-learning in secondary day school programs in the TDSB reveals intensified inequalities that map geographically in areas divided by class and race, serving students in schools with greater learning opportunities. By this, I refer to the concentration of e-learning students in schools that are ranked highly on the TDSB’s Learning Opportunity Index (LOI). I also show how the TDSB leverages e-learning to facilitate private–public partnership with Canadian International School (CIS), Vietnam. It is a program that accredits Vietnamese students with an Ontario Secondary School Diploma so that they better qualify for university programs abroad. In the context of these results, I argue that that the promise made by e-learning is impossible to fulfil because it is a technology that reinforces merit-based schooling systems that tend to reproduce social and cultural hierarchy. Social scientists working on educational issues have long identified how inequality is spatialized, particularly as a dynamic of exclusionary processes and inclusionary activities that reproduce hierarchies. These hierarchies condition student identity and perpetuate systems of disadvantage and violence wrought by settler colonialism, anti-Black racism, gender discrimination, and conceptions of disability within a global capitalist economy. Systems, however, are not static. Systems can be contested. While emphasizing the institutional nature of oppression, I hold schooling systems in tension with the insights of students, whose desire for a more inclusive society produces the force that makes progress possible. It is the responsibility of public education to realize this desire, for the benefit of all students. In a time of deepening cuts, education faces a crisis manufactured by social divestment, rising income inequality, and entrenchment of cultural hierarchies that discredit diversity as a value that can produce structural transformation and social justice. As an integral part of communities, schools must harness the power of people, rather than technology, to respond to this crisis.

Keywords: cultural and social geography
education
e-learning
ethnography
K-12
social justice
Advisor: Hunter, Mark
Characterizing Resting-State Brain Dynamics in Individuals with and without Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social communication as well as restricted, repetitive and stereotyped behaviours. ASD is a highly heterogeneous disorder, with a broad range of the types and severities of symptoms that can be displayed. It has been proposed that ASD is characterized by abnormal functional connectivity (FC) between brain regions, which can be defined as the correlations of functional magnetic resonance imaging (fMRI) time series between pairs of regions of interest. However, studies of FC in ASD have presented mixed results. Further, it has been suggested that there is a complex developmental trajectory of FC in ASD. Inconsistent results across studies may, in part, be related to differences in fMRI data processing strategies, as well as heterogeneity of sample characteristics. Other aspects of brain dynamics, including variability and complexity of blood oxygen-level dependent (BOLD) time series, are not well characterized in ASD. The goal of this dissertation is to analyze resting-state brain dynamics in ASD, and to address the inconsistencies in previous studies of resting-state fMRI in ASD. Study 1 involves the characterization of FC-based subtypes of ASD and typically developing (TD) participants to elucidate unique relationships between FC and behaviour. In Study 2, different fMRI data processing strategies are examined to determine the effects of these processing choices on group differences in FC in children and adolescents with and without ASD. Study 3 involves examining BOLD signal variability and complexity, and relating these metrics to structural connectivity, age, and behavioural severity. Overall, these studies reveal the importance of considering subtypes of ASD and TD individuals, the effects of preprocessing strategies, and relationships between brain dynamics and brain structure, age, and behavioural severity when analyzing resting-state brain dynamics in those with and without ASD.

Keywords: Autism spectrum disorder
Functional connectivity
Functional magnetic resonance imaging
Multivariate statistics
Resting-state
Advisor: McIntosh, Anthony R
Exploring Online Engineering Education for Sustainable Development: Reconceptualizing Curriculum at Scale

Projected growth in urban centers will require increased engineering talent and resources to facilitate the infrastructure demands of growing cities (Ibrahim et al., 2016). This study sought to understand how universities in Kenya, Rwanda and Canada were currently equipped to scale and support engineering programs on sustainable development. I travelled to Kenya and Rwanda in July of 2016, and to Canada in August and September of 2018, to study engineering programs and interview faculty members at five universities. Pinar’s (1975) method of currere was used as a theoretical framework for studying online engineering education in post-colonial contexts. The study paired the theoretical framework with a case study methodology. The study generated six themes related to scaling engineering education for sustainable development online. The themes are the engineering curriculum, online learning, accreditation, the progression from an engineering graduate to a professional, the government influences and international influences. The findings provide insights for a researcher and an educator to consider when studying and designing online engineering education for sustainable development at scale. The findings emphasize the importance of incorporating hands-on solutions in the engineering curriculum, the need to negotiate with the stakeholders from the universities, accreditation boards, local and international governments, and the importance of contextualizing the curriculum to the students and their environments. The findings also revealed the significant involvement of China in government-sponsored infrastructure projects in East Africa, the increase in the number of MOOCs on sustainable development, the importance purposefully filling academic and development spaces in a good way, and how the method of currere can be used to bridge a gap between engineering and education university departments. Further research is needed to explore how educators and researchers can develop the necessary skills to collaborate with individuals with different worldviews, understand the impact that China’s involvement in East Africa has on sustainable development and engineering education, interview other stakeholders identified by the participants, and, how future sustainable development projects will affect engineers and their environments.

Keywords: autobiography
currere
engineering
engineering education
sustainability
technology
Advisor: Brett, Clare
Necroptosis and its Interactions with Focal Adhesion Kinase (FAK) and Extracellular Receptor Kinase (ERK1/2) following Optic Nerve Injury

Glaucoma is the most prominent blinding disease in the world. It is irreversible and due to its slow progression, patients often do not notice their decreased visual field until it is too late and the damage is irreversible. Retinal ganglion cells are an essential step in the visual pathway connecting retinal photoreceptors to their targets in the brain, and they are the predominant celltype affected by glaucomatous degeneration. Although glaucoma has traditionally been associated with increased intraocular pressure, treatments designed to affect it have met with limited success. This has led to a greater recognition of the importance of intracellular deathinducing mechanisms in the disease. Due to the protracted nature of neuron death in glaucoma, apoptosis has been regarded as the disease’s primary, and therefore most studied, causative mechanism. However, recent advances have uncovered many more regulated neuron death mechanisms, of which necroptosis is a prominent member. Necroptosis activation has been detected in other central nervous system conditions, such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, as well as following ischemia in the brain and retina. The goal of this thesis is to examine the activation and role of necroptosis in the retina following optic nerve damage, a commonly used injury model to study glaucomatous neuron death. Some of thefactors associated with necroptosis have also been associated with cell-survival mechanisms,possibly contributing to aberrant cell-cycle re-entry. Therefore, the interplay between necroptosis and some prominent survival-inducing peptides is also examined. The goal `of this research is to provide a basis for future work addressing neurodegeneration as a result of glaucoma or other neurodegenerative disease.

Keywords: Extracellular Receptor Kinase 1/2
MLKL
Necroptosis
Retina
RIP Kinase
Vision
Advisor: Koeberle, Paulo D