VictorJuiz/thesis huggingface dataset:
“This Body Has Fought Hard to Be Here!” —Unearthing Mishritata: Using Drama to Map the Multiple Minoritization of Queer Desi/South Asian Young Adults in Toronto

Despite the emergence of Queer People of Colour perspectives in education research, the lives of Queer Desis/South Asians have received little attention beyond “coming out” narratives. Addressing this absence, this mixed-methods study uses a community-grounded approach and mobilizes Desi ontoepistemologies to centre storytelling. Specifically, this study explores and examines how five Queer Desi/South Asian young adults (18–35 years) understand and negotiate their identities in Toronto, Canada. Data were collected over 18 months in the form of a quantitative survey (N = 77), kathās (an extension of life stories), 20 hours of applied drama activities, and “time-pass” (meaning spending time with kin) with five participants, as well as archival research into the history of the community’s presence and activism in Toronto. Analyses yielded a rich framework of mishritata (mixedness) for examining the borderlands social location for Queer Desis/South Asians, mobilized methodologically and analytically to centre embodiment and affect as powerful sites of knowledge production. This project enriches affective ontoepistemological understandings of the quotidian lives of Queer Desi/South Asian young adults across real and imagined borders. It further illuminates how drama can be used to conceptualize new models of subjectivity, consciousness, and (un)belonging to address these concerns. Survey data and life-stories analyses yielded key “disruptions” that pushed against conventional understandings of resilience, kinship, counterspaces, and structural and systemic complicities. Using drama, participants exhibited what I term khush—an organizing strategy that extends resilience research and functions as a consciousness and practice of mishritata through three discrete sensibilities: a dunya-paar (world-crossing), a transgressive, and a strategic sensibility of unbelonging. This research calls on educators to better understand placemaking for multiply minoritized individuals living in and moving between their various communities, within and beyond sites of formal learning. By examining how drama provides a space for Queer Desis/South Asians to creatively and collaboratively engage in “truth telling” and knowledge building about their multiply minoritized experiences and future imaginings, this research contributes to the fields of ethnic studies, queer studies, borderlands studies, critical youth studies, higher education and student-development theory, applied drama/theatre, mixed methods, and community-based research.

Keywords: Applied drama methods
Desi/South Asian
Intersectionality
LGBTQ+
Mixed methods research
Queer
Advisor: Gallagher, Kathleen M
RNA-binding Proteins and RNA-DNA Hybrids Regulate Repetitive DNA Stability in Health and Disease

The preservation of genome stability is essential to proper cellular function. Repetitive DNA sequences, such as the ribosomal DNA repeats (rDNA) and transposons, represent a large portion of eukaryotic genomes. Due to their repetitive nature, these loci are prone to aberrant recombination. In fact, rDNA repeat instability and increased transposon activity are hallmarks of neurodegenerative disease. Thus, cells employ multiple mechanisms to safeguard the integrity of repetitive loci. The RNA-binding protein Ataxin-2 (Pbp1 in yeast) regulates the stability of rDNA and yeast Ty1 retrotransposons. Interestingly, the human protein (ATXN2) undergoes trinucleotide repeat expansion in the neurodegenerative diseases spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis. Here, we create yeast models of Ataxin-2-linked neurodegeneration. SCA2-modeling cells exhibit Ty1 protein aggregates, which aberrantly localize to the nucleolus and hyperactivate the degradation of non-coding RNAs transcribed from the intergenic spacer of the rDNA repeats. This induces rDNA recombination and premature aging. Thus, our yeast models suggest trinucleotide repeat expansion of Ataxin-2 represents a gain-of-function mutation that may trigger neurodegeneration through alterations to the stability of repetitive DNA, uniting the “rDNA instability” and “protein aggregation” theories of aging. In addition, we discover a new mechanism that drives the mobility of retrotransposons via RNA-DNA hybrids. RNA-DNA hybrids are duplex nucleic acid structures that form when an RNA molecule binds to its DNA template. RNA-DNA hybrids can generate a tri-nucleic acid structure known as an R-loop that is composed of the RNA-DNA hybrid and a displaced single-stranded non-template DNA. We find that RNA-DNA hybrid structures and R-loops can form on extra-chromosomal Ty1 cDNA in yeast, but these structures drive Ty1 retromobility through distinct mechanisms. Ty1-associated R-loops drive retromobility through the canonical integration pathway, while Ty1-associated RNA-cDNA hybrids drive retromobility through a non-canonical homologous recombination-dependent pathway. Thus, the structure of an RNA-DNA hybrid (duplex versus triplex) may help dictate the mechanism through which it mobilizes transposable elements. Taken together, our yeast genetic studies reveal how intergenic non-coding RNAs and protein aggregates associated with repetitive DNA loci may collaboratively drive neurodegeneration and how RNA-DNA hybrids and R-loops differentially contribute to the mobilization of transposable elements.

Keywords: Aging
Genome stability
Non-coding RNA
Repetitive DNA
Retrotransposons
Ribosomal DNA
Advisor: Mekhail, Karim
Branding the Regime: China’s Soft Regime Promotion in the post- Reform Era

Little evidence suggests that the rising China is engaged in regime promotion as did historical cases. Given the seeming non-finding, what has China been actively doing to influence other regimes? How does it do it? Why does China’s approach to regime promotion assume the particular form? This dissertation argues that China indeed does not promote its regime in the conventional sense – to proselytize its regime and instigate regime change abroad. Instead, China engages in “soft regime promotion” – the active dissemination of knowledge about its regime aimed primarily at branding the regime as successful, competent, and peculiar. In the current system, the low status of an authoritarian regime poses an existential challenge to its legitimacy and survival. Thus, status pursuit is a crucial motive behind soft regime promotion that is under-studied in the existing literature. China’s soft regime promotion corresponds to the status enhancement pathway of social creativity: it targets a reference group to its advantage, the developing countries; it shelves the factor of regime type and attaches importance to issues of state governance; and it puts a premium on the role of the state as well as a competent ruling party. China’s soft regime promotion is rooted in the regime’s self-understandings. Absent a coherent regime ideology, the Communist Party of China has come to enshrine itself as the defining feature of the regime and boasted about its achievements in governing China. China’s ideological status quo not only precludes the proselytizing of a wholesale model, but also shapes the “space of possibilities” in which agents of regime knowledge transfer “improvise” varied knowledge about the Chinese regime. China specifically engages in the conspicuous giving of regime knowledge – hosting training and exchange activities for elites from developing countries. This is done through two major channels: in the name of the state, China hosts degree education programs and training programs under the banner of foreign aid; and in the name of the Party, various formats of exchange activities have been held. Within and across both channels, variations are found in the regime knowledge transferred and the dynamics of principal-agent relationships.

Keywords: China
Democracy
Knowledge transfer
Regime promotion
Status
Advisor: Gunitsky, Seva
Shared Heuristics: How Organizational Culture Shapes Asylum Policy

What explains cross-national variation in asylum recognition rates? This is an important question that has implications for international law, public administration, and judicial politics. In many countries, bureaucratic agencies dominate the quasi-judicial process through which asylum-seekers are granted protective status (also known as refugee status determination or RSD). Refugee policy is unique in that it is the only form of migration policy that is codified into international law, Moreover, the United Nations High Commissioner actively monitors and guides implementation across the world. My study focuses on explaining developed countries with consistently high or low recognition rates. Comparing countries with varying degrees of procedural rights, influential refugee advocates, and experience hosting immigrants, my dissertation identifies the role of entrenched beliefs about asylum-seekers that stem from professional experience as the driver high recognition rates in Canada and of low recognition rates in Ireland, Japan, and South Korea. In this way, my study challenges conventional political science explanations of asylum policy that focus on international norms, political incentives, or the institutional rules of refugee status determination (RSD) procedures. Furthermore, it uses a mixed methods approach to both identify bureaucratic culture and test its effects as well as to illustrate that bureaucratic culture is not a reflection of public attitudes toward refugees.

Keywords: asylum policy
bureaucracy
immigration
refugees
Advisor: Hansen, Randall
The Ontogeny and Vulnerability of Lapatinib Drug Tolerant Persisters in HER2-positive Breast Cancer

HER2-positive breast cancer accounts for 15-20% of all breast cancer cases. Early-stage HER2-positive breast cancer is typically curable with surgery and trastuzumab/chemotherapy combinations, but most metastatic HER2-positive breast cancer inevitably recurs following treatment. Drug-tolerant persisters (DTPs) have been defined as a subpopulation of cancer cells that can survive tyrosine kinase inhibitor or chemotherapeutic agents in vitro, and two independent reports show that DTPs can subsequently acquire resistance-conferring mutations. Hence, these cells are potential reservoirs for the development of drug resistance. My work showed that a subset of HER2-positive breast cancer cell lines can give rise to DTPs after lapatinib treatment. Lapatinib DTPs showed re-wiring of the PI3K/AKT/mTORC1 pathway, such that they are more dependent on PI3K than AKT for mTORC1 activation and survival. One AKT-independent survival pathway was mediated through the transcriptional up-regulation of SGK3 in a subset of lapatinib DTPs. Transcriptional profiling revealed that two distinct transcriptional programs were activated in response to lapatinib, and these correlated with the SGK3 dependency of lapatinib DTPs. Furthermore, SGK3-dependent cell lines are uniquely sensitive to lapatinib and endocrine therapy (fulvestrant or estrogen deprivation) combinations, compared with SGK3-independent cell lines. In parallel, my work provides insight into the ontogeny of DTPs. Bar-coding experiments revealed that lapatinib DTPs are not part of a pre-existing hierarchy, but instead are generated stochastically. Nevertheless, single-cell RNA sequencing studies (scRNA-seq) in at least one HER2+ cell line (BT474), a sub-population of cells pre-exist in a DTP-like state (pre-DTPs), and enriched for multiple BT474-DTP differential expressed genes (DEGs). Antibodies against one such “pre-DTP” marker, NPY1R, enabled the prospective purification of lapatinib DTPs. NPY1R-high cells also enriched for multiple BT474-DTP markers, providing further confirmation of the presence of the pre-DTP state prior to lapatinib exposure. Intriguingly, NPY1R-high cells showed elevated basal and induced estrogen receptor transcriptional activity in response to lapatinib, compared with NPY1R-low cells. Collectively, my results support a pre-existing and stochastic model for lapatinib DTPs.

Advisor: Neel, Benjamin G.
Outcomes Following Resection for Esophageal Cancer in Ontario

Background Esophageal cancer (EC) incidence is increasing in Ontario, and there is a need to assess outcomes for this disease on a population level. This thesis sought to (1) create a cohort of patients with EC in Ontario; (2) evaluate whether surgery at regionalized thoracic centres is associated with reduced readmission following esophageal cancer resection; and (3) compare thoracic centres’ treatment patterns, surgical outcomes, and survival to non-thoracic centres for resected EC, and assess variation across thoracic centres. Methods Using linked administrative healthcare and abstracted surgical pathology data, we created the Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO) from 2002-2014, and focused on resected EC patients. Descriptive statistics and funnel plots were used to compare treatment patterns, surgical outcomes, and survival at thoracic and non-thoracic centres, and assess variation. Multivariable logistic and Cox proportional hazards models were used to evaluate whether surgery at thoracic centres was associated with readmission, postoperative mortality, and survival. Results We identified 3,880 patients who underwent surgery for EC. Of these, 3,670 survived to discharge and were included in the readmission analysis. Overall, 27.7% were readmitted within 90 days of discharge. Surgery at thoracic centres was not significantly associated with 90-day readmission. Of 3,880 resected patients, 2,213 had pathology data available and were included in the treatment patterns, surgical outcomes, and survival analysis. Compared to patients at non-thoracic centres, patients at thoracic centres received more neoadjuvant therapy, had similar margin rates and lymph node harvest, experienced lower postoperative mortality, and had similar overall survival. Across thoracic centres, neoadjuvant therapy use varied from 16.4-81.6%, positive margin rates varied from 8.2-29.6%, median lymph node harvest varied from 7-20 nodes, postoperative mortality varied from 0-18.7%, and median survival varied from 17-26 months. Conclusion We created the PRESTO database to enable EC research in Ontario. Using these data, we observed patients experienced similar outcomes at thoracic and non-thoracic centres. We also documented significant variability in treatment patterns and outcomes among thoracic centres. Further quality improvement efforts are needed for surgical EC care in Ontario. The PRESTO platform can be leveraged to initiate this quality improvement work.

Keywords: clinical epidemiology
esophageal cancer
health policy
health services research
quality improvement
surgical outcomes
Advisor: Coburn, Natalie G
Darling, Gail E
An Army with a State or a State with an Army? The Military and Post-Conflict Governance in Uganda and Rwanda

Post-conflict Uganda and Rwanda have had the experience of two distinctive political regimes, the Uganda National Resistance Movement (NRM) and the Rwandan Patriotic Front (RPF), which first struggled with the aftermath of devastating civil war. In both countries, the state had largely collapsed and became bitterly contested by belligerent factions, leaving both regimes with the challenge of re-building and consolidating state power. Both regimes were essentially led by a small group of elites who saw the military and the restoration of political order as central to post-conflict state reconstruction. However, the process of state reconstruction in both countries produced strikingly different outcomes: the emergence of a civil authoritarian regime in Uganda in which the military is clearly subordinate to the interests of the political regime, versus a military authoritarian regime in Rwanda, where the interests of the military are much more obviously paramount in how political power is structured. What accounts for this? Why did these two regimes adopt such different state-building strategies? My dissertation draws from original qualitative data collected from Uganda and Rwanda to explain strategies used by actors that win civil wars to restructure the authority and reach of the state in a new postwar society. I show how the postwar regime in Uganda inherited what I call a “residue” social structure, characterised by the persistence of resilient and well-entrenched elite interests. A key finding of my PhD dissertation is that, to gain trust and legitimise his rule, the postwar regime leader in Uganda adopted a strategy involving co-optation of, collaboration with, and concessions to these interests, which ultimately led to the creation of a broad-based system of government designed purposely to accommodate varying interests of these social groups. By contrast, the post-genocide regime in Rwanda inherited a political structure that was completely shattered--without much “residue”. To gain legitimacy, the elites within the RPF (who had won the war) exploited the political vacuum to transform what had been a guerrilla group into a strong centralised military regime, justifying the creation of a strong and cohesive military regime as a buttress against genocide.

Keywords: Civil-military relations
Elite Politics
Governance and development in Africa
Post-conflict state reconstruction
Postcolonial African state
Advisor: Handley, Antoinette
Handley, Antoinette
Autobiographical Strategies in Early Modern English, Irish, and Iberian Women's Letters (1540–1640)

Taking a comparative approach, this thesis puts into conversation the letters of writers from different language traditions. Reading the extant correspondence of four women letter-writers between 1540–1640 in England, Ireland, Spain, and Portugal, the thesis focuses on the use of the rhetorical tropes of exemplarity and exceptionality. The thesis argues that women letter-writers construct their epistolary personas as exemplary or exceptional in collaboration with their correspondents in order to increase their authorial agency. Unapologetic about their actions—beyond moments of rhetorical modesty—these writers attempt to increase support and minimize opposition by courting allies who are already in positions of influence. Their invocation of exemplarity and exceptionality is based on the writers’ autobiographical experiences, allowing them to develop epistolary personas that are effective in their correspondences. The first two chapters examine women whose correspondences position them as “exceptional” figures, both in their own letters and the letters of others. Chapter One reads the correspondence of Luisa Sigea, a humanist working at royal courts in Portugal and Spain. She invokes the praise she received from Pope Paul III for her exceptionality in her letters to further her later career. Chapter Two looks at the surviving letters of Irish clan leader Gráinne Ní Mháille. The combination of a handful of petitions by Ní Mháille in the 1590s with a large bureaucratic correspondence about her from the 1570s and ’80s illuminates the ways in which English bureaucrats’ interpretation of her actions as “exceptional” informs Ní Mháille’s own self-presentation in her petitions. The third and fourth chapters examine the letters and documents of two writers whose “exemplary” lives are constructed in negotiation with their epistolary personas. In Chapter Three, Spanish noblewoman Luisa de Carvajal y Mendoza represents her often-radical religious practices as part of the exemplary tradition of martyrs and saints, culminating in her move to London in 1605, where she hopes to evangelize Catholicism and achieve martyrdom. Chapter Four looks at Elizabeth Cary as she attempts to reconcile her recusant Catholicism with her role in a Protestant family and kingdom by positioning herself as an exemplary wife, mother, daughter, subject, and Christian.

Keywords: early modern women
England
Ireland
Spain
women letter-writers
Advisor: Magnusson, Lynne
SLOW BURN: Subversion and Escalation in Cyber Conflict and Covert Action

This thesis argues that the low intensity of cyber conflict reflects the fact that cyber operations have been primarily useful as means of subversion rather than warfare. Established wisdom that conceives of cyber conflict as a novel form of warfare defined by its speed the escalatory properties of cyber weapons. In practice, it has been marked by persistently low intensity and escalation has not occurred. This mismatch between theory and practice presents a puzzle. Subversion, in contrast, is a slow-burning and low intensity alternative to the use of force that is strategically attractive but operationally limited in effectiveness. It is strategically attractive because it promises to exert influence over competitors at lower costs and risks compared to force projection. These advantages are the result of its indirect and covert mechanism of action, which secretly undermines and manipulates an adversary’s own capabilities to produce detrimental effects against the former and erode its capacity to resist. However, this mechanism comes with three inherent constraints that limits effectiveness: subversion is slow, the intensity of effects is limited and it is unreliable. The strategic role and operational constraints of subversion explain the low intensity of cyber conflict. Cyber operations target new technologies but rely on the same operational mechanism of exploiting vulnerabilities in secret—hence they are expected to face analogous constraints. The thesis develops a grounded theory based on a structured focused comparison of a historical and contemporary case of subversion. The cases chosen are the Soviet campaign to suppress the Prague Spring and the Russian campaign to suppress the Euromaidan movement in Ukraine 2013-2018. These cases are most-similar except for the technology used. This comparison confirms expectations, showing that technological change has not altered the quality of subversion. Counterintuitively, however, the analysis reveals the operational constraints of cyber operations reinforce rather than reform its slow-burning and low intensity character. Contrary to prevailing threat perception of critical infrastructure strikes, cyber operations prove slower, more expensive and less effective than traditional sabotage operations.

Keywords: cyber conflict
cybersecurity
Czechoslovakia
grey zone
subversion
Ukraine
Advisor: Deibert, Ronald J.
Pauly, Louis W.