VictorJuiz/thesis huggingface dataset:
The Ethics of Theatre: Community, Selfhood, and Alterity in Early Modern Drama
Keywords: Drama
Ethics
Shakespeare
Theatre

This thesis explores the ethical stakes of early modern English drama at the critical intersection of religion, poetry, rhetoric, and performance studies. The theatre of the period was a site of competing sources of authority, between religious, philosophical, and poetic perspectives that advocated idealism and virtuous conduct, and rhetorical and performance practices that privileged contingency and probability. The resulting tensions were represented on the stage through various modes of alterity, through which playwrights explored the shifting power dynamics between individuals and the communities to which they belonged. My study argues that the theatre’s defining ethical position must be understood in relation to representations of exclusion in particular, whereby individuals are alienated from their respective communities based on religious, ethnic, racial, sexual, and cultural differences. Such forms of exclusion are countered by marginalized characters through the development of linguistic strategies that seek to offset their loss of authority. Each of my chapters explores different aspects of that process as represented in plays by Christopher Marlowe, William Shakespeare, and Ben Jonson. In my first chapter, I argue that damnation in Doctor Faustus constitutes a form of social exclusion that highlights the coercive mechanisms of religious community formation, which Marlowe dramatizes through what I call an aesthetics of self-conceit, a form of alienation achieved through habit formation. My second chapter looks at expressions of hatred in relation to religious communal belonging in Othello. I argue that the play highlights the ethically fraught means through which Christianity accommodates alterity within its worldview. In the third chapter, I investigate how linguistic practices, particularly religious rhetoric, destabilize political authority in Measure for Measure. My last chapter discusses Jonson’s poetry and drama, specifically the Epigrams, Poetaster, and Volpone. I argue that Jonson develops an exclusionary poetics that enables him to maintain an attachment to his idealized self-conception as a poet in an unruly theatrical environment where authority was perpetually contested between playwrights, actors, and audiences. Through my linguistic analysis of these dramatic texts, I provide new interpretive strategies for investigating the function of ethics in the early modern theatre.
The Role of HSP90C in Chloroplast Maturation and Thylakoid Protein Transport
Keywords: Chaperone
Chloroplast
Hsp90
Protein Homeostasis
Protein Translocation
Sec Translocon

The chloroplast is an organelle that has a primary role in performing photosynthesis in green plants and contains thousands of proteins. Since most chloroplast proteins are synthesized outside of the chloroplast on cytosolic ribosomes, they are imported into chloroplasts in mostly unfolded states. A protein quality control system in the chloroplast is then responsible for their correct folding, assembly, and repair, or facilitate their removal if terminally damaged. The composition and translocation process of the protein import machineries on the chloroplast envelopes and the thylakoid membranes have been studied in-depth; however, how stromal factors are involved in bridging chloroplast membrane import and thylakoid transport of thylakoid proteins is still poorly understood. In this thesis, I elucidated a role and mechanism of action for the essential plastid HSP90 family heat shock protein HSP90C in this process. Using a thylakoid lumen-localized subunit of the oxygen evolving complex, I demonstrated that PsbO1 is tightly regulated by the HSP90C complex in the stroma. By analyzing the chloroplast maturation process, the essential role of HSP90C and its ATPase activity in regulating and balancing the influx and efflux of PsbO1 fusion proteins within the stroma was demonstrated. A specific role of HSP90C in forming a guiding complex that interacts with the SEC translocation system and facilitates ATP-dependent thylakoid protein targeting and transport was proposed. These studies reveal critical roles of HSP90C in the chloroplast and thus provide new insights into the molecular mechanism of HSP90 family molecular chaperones in regulating organellar protein homeostasis.
The Development of Assays for Detecting Proximal Phosphorylation and Covalent Modification of Proteins
Keywords: Assay Development
Chemosensor
Covalent
Drug Discovery
Electrophilic Warhead
Proximal Phosphorylation

Bioassays are important tools in translational research for several disciplines including medicinal chemistry, molecular recognition and chemical biology. Achieving success in bioassays represents important milestones in many pharmaceutical pipelines and disease diagnostics, and as such, must be designed and fine-tuned to produce meaningful, robust, and reproducible results. This thesis focuses on the design and development of unique bioassays for two important medicinal chemistry fields of research. The first is the selective detection of proximally phosphorylated biomolecules, including peptides, proteins, nucleotides, and phospholipids. Proximal phosphorylation affects many cellular functions including protein localization, degradation, signalling cascades, gene expression, and the cell cycle. Importantly, the dysregulation of proximal phosphorylation motifs has been implicated in aberrant protein states, including the overactivation of kinases in oncology and protein aggregation in neurodegenerative diseases. Similarly, phosphate-induced anionic charge within phospholipid membranes is an important biomarker for mammalian cell apoptosis and can be used to selectively detect bacterial infections. To achieve this goal, a previously discovered fluorescent excimer chemosensor was characterized and next generation chemosensor libraries were designed and synthesized. Chemosensors were used for proximal phosphate detection in numerous biologically-relevant applications with a variety of assay types including fluorimetry, microscopy, polyacrylamide gels and flow cytometry. The second objective in assay development was to assess a modular electrophilic warhead platform for novel covalent inhibitors. Through nucleophilic aromatic substitution methodology, selectively derivatized polyfluorinated benzene rings were synthesized to construct an electrophilic warhead library that could be electronically and sterically tuned for specific protein interactions. To assess the inherent reactivity of the electrophilic warhead, a fluorescent chemosensor-based fluoride-release assay was developed which revealed a diverse range of intrinsic cysteine reactivities. As a proof-of-concept, the electrophilic warhead platform was applied to a clinical covalent tubulin inhibitor for improved potency and pharmacokinetic properties. The modified tubulin inhibitors were assessed in a variety of bioassays that demonstrated both the success and potential of the warhead platform. Across both objectives, the development of bioassays has produced technologies and insights that can overall benefit chemical biology, molecular recognition, and medicinal chemistry research.
Mountain Industries and Votive Dedications in Roman Aquitania and Hispania
Keywords: Aquitania
beekeeping
Hispania
mining
onomastics
silvopastoralism

This thesis investigates the participation of the local population in economic activities in areas belonging to two contiguous Roman provinces, southern Aquitania and central Hispania Tarraconensis, during a period of some three centuries (first century BCE-second century CE). During the Principate, these mostly mountainous regions saw the growth of mining and quarrying communities, but the investigation here presented includes other economic activities as well. The thesis attempts to reconstruct facets of the relationship between the Roman mining industry and several traditional economic activities in these mountain zones: pig farming, forest exploitation, and beekeeping. In areas of the Roman west where mining and quarrying were undertaken or expanded under the Romans, an analysis of cultic preferences visible in inscribed Latin votive dedications allows us to trace shifts in local economies surrounding this industry but also several others. Mountain areas, where Roman mining and quarrying communities were frequently established because of existing mineral deposits, are useful locations in which to observe economic motivations in votive dedications in a controlled, measurable way. Several mountain industries tied to their area’s unique natural resources and geography, for example, pitch production, often become visible and individualized in the votive record of such areas. Votive dedications in mining districts represent a microcosm of industrial change allowing scholars to understand hitherto unexplored features of local participation in the provincial Roman mining industry but also the attitudes of local individuals to traditional economic activities in these same districts.
Transcriptomic Characterization of Primary B Cell Acute Lymphoblastic Leukemia Identifies Novel Protein Biomarkers of High-risk Disease and Novel Mechanisms of L-asparaginase Resistance
Keywords: Cancer
Diagnosis
Genomics
Immunology
Leukemia
RNA sequencing

There is an unmet medical need to improve identification of B cell acute lymphoblastic leukemia (B-ALL) patients at high-risk (HR) for relapse, so that they can receive more aggressive or experimental therapies. Treatment with ABL-targeted therapies has improved outcomes for patients with the Philadelphia (Ph) chromosome that encodes BCR-Abl fusions. “Ph-like” ALL is also characterized by kinase activating mutations that are therapeutically targetable, but they cannot be readily identified using routine clinical methods. The overall goal of my project was to use transcriptomics and single cell immune profiling to improve identification of HR “Ph-like” ALL cases and to identify mechanisms of ALL chemo-resistance. I developed an RNA-Sequencing (RNA-seq) data analysis pipeline and identified fusion transcripts, mutations and a gene expression signature associated with Ph-like cases in a cohort of 45 “B-Other” ALL cases that lacked clinically detected mutations. I then used single cell flow and mass cytometry to show that expression patterns of five surface protein encoding genes (SPEG) robustly distinguished Ph-like cases with ABL1 or CRLF2/JAK2 mutations that promote STAT5 activation from non-Ph-like cases of “B-Other” ALL. Thus, by integrating data from several “multi-omic” approaches, I defined a novel SPEG classification method that can rapidly identify Ph-like ALL cases with targetable signaling mutations. Unfortunately, about 12% of relapsed B-ALL patients are refractory to treatment with L-asparaginase (L-asp), long used as a front-line chemotherapy for ALL cells because they lack Asparagine synthetase (ASNS) and thus require extracellular L-Asparagine. However, few studies have identified mechanisms of L-asp resistance in primary ALL cells. Through bioinformatic and in vitro approaches, I show that deregulation of ASNS expression by promoter fusions or by RAS/MAPK pathway activation promotes L-asp resistance in B-ALL. These data suggest that RAS-targeted therapies could improve outcomes for RAS-mutated ALL. Overall, my work has provided a new method that could be used for routine diagnosis of HR Ph-like ALL cases likely to have targetable signaling mutations. Additionally, I have identified RAS/MAPK signaling as a potential therapeutic target to enhance induction of remission and more effectively treat relapses in patients with RAS-mutated B-ALL.
The Role of RNF168 and Novel Genetic Vulnerabilities in BRCA1/2-mutant Cancers
Keywords: BRCA1/2
Breast Cancer
Cancer Therapy
DNA Damage Signaling Repair
Ovarian Cancer
R-loops

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) genes considerably increase breast and ovarian cancer risk. Given that tumors with these mutations have elevated genomic instability, they exhibit relative vulnerability to certain chemotherapies and targeted treatments based on poly (ADP-ribose) polymerase (PARP) inhibition. However, the molecular mechanisms that influence cancer risk and therapeutic benefit or resistance remain only partially understood. BRCA1 and BRCA2 have also been implicated in the suppression of R-loops, triple-stranded nucleic acid structures composed of a DNA:RNA hybrid and a displaced ssDNA strand. In this thesis, I report that loss of RNF168, an E3 ubiquitin ligase and DNA double-strand break (DSB) responder, remarkably protects Brca1-mutant mice against mammary tumorigenesis. I demonstrate that RNF168 deficiency results in R-loop accumulation in BRCA1/2-mutant breast and ovarian cancer cells, leading to DSBs, senescence, and loss of viability. Using interactome assays, I identified RNF168 interaction with DHX9, a helicase involved in the resolution and removal of R-loops. Mechanistically, RNF168 directly ubiquitylates DHX9 to facilitate its recruitment to R-loop-prone genomic loci. Consequently, loss of RNF168 impairs DHX9 recruitment to R-loops, thereby abrogating its ability to resolve these structures. Furthermore, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, I demonstrate that depletion of MEPCE in a BRCA1-deficient setting leads to RNA polymerase II (RNAPII) redistribution and subsequent R-loop accumulation and replication stress, contributing to transcription- replication collisions. These collisions compromise genomic integrity resulting in loss of viability of BRCA1-deficient cells. I also extend these findings to another RNAPII-regulating factor, PAF1. This study identifies a new class of synthetic lethal partners of BRCA1 that exploit the RNAPII pausing regulation and highlight the untapped potential of transcription-replication conflict-inducing factors as unique therapeutic targets for treating cancers associated with BRCA1 mutations. Together, data presented in this thesis highlight novel vulnerabilities of BRCA1/2 mutant cancers and link these vulnerabilities to fundamental molecular mechanisms that govern cancer development and progression.
The Paradox of Equity in Ontario's Public Education System: The Making of an Epistemology of Ignorance
Keywords: Education
Equity
Ignorance
Race
Racism
School

This dissertation research examines equity work in the Ontario public education system from 2009 to 2020. This work forwards the category of “equity leader” to draw attention to educators who are tasked with teaching entire school boards about equity and inclusion work. The dissertation demonstrates how school boards in Ontario profess through equity discourse, polices, and publications that they support notions of equity and inclusion, yet the barriers to equity work continue to be reproduced. Equity leaders’ experiences provide a rich platform for highlighting the paradoxical nature of equity work and systemic racism in education, and how organizations are complicit in systemic racism even while they profess to believe in equity principles. In Ontario, equity leader roles span the associate director, superintendent, principal, teacher, and consultant positions. Their daily duties include supporting equity and inclusion work from junior kindergarten to Grade 12 as well as supporting business staff and working with school communities. Through interviews with twenty-one equity leaders from the Toronto District School Board, Peel District School Board, and York Region District School Board, as well as document analysis, the study demonstrates how equity leaders do equity work in education systems that are racist and colonial. Equity leaders’ knowledge and skills demonstrate how people navigate, resist, and contend with systemic racism, and exert agency within institutions that are racist. Using Charles Mills’ racial contract conceptual framework, which posits that white supremacy is predicated upon an epistemology of ignorance and a commitment to a racial fantasyland, the multifaceted paradox of equity work is explored.
The State at the Margins: The Politics of State Social Assistance and Citizenship in Rural Kenya and Tanzania
Keywords: Cash Transfers
Citizenship
Kenya
Social Policy
Statebuilding
Tanzania

This dissertation leverages both inter-state and intra-state comparisons to interrogate why cash transfer programs in Kenya and Tanzania have had profoundly different impacts on recipients’ perceptions and practices of citizenship. First, it leverages intra-state comparisons to compare Luo communities receiving government cash transfers with those not receiving cash transfers to examine the impacts of cash transfers of citizens’ perceptions of and access to the structures of the state. It finds that cash transfers have had transformative impacts for citizens’ perceptions and practices of citizenship in Kenya but not in Tanzania. Second, it leverages inter-state comparisons amongst these Luo communities on either side of the Tanzania-Kenya border, who have a shared history language and culture, to elucidate why similar cash transfer programs have had profoundly different impacts on citizenship. This dissertation argues that the impacts of cash transfer programs are mediated by post-colonial histories of national building which structure the formal institutions through which cash transfers are implemented and the informal institutions that shape commonly held understandings of the state’s role vis-à-vis the citizen. Where citizens have been historically excluded from the central resources of the state, the state provision of cash transfers can provide citizens new avenues through which they can interact with and make demands on the state. In Tanzania, the post-colonial nation-building project created an inclusive sense of citizenship that is deeply rooted in a cohesive national identity, perceptions of community and norms of reciprocity. The introduction of means-tested cash transfer programs in Tanzania, then, did not challenge commonly held understandings of citizenship and of the state’s role vis-à-vis the citizen. In contrast, in Kenya, a post-colonial era marked by the distribution of state resources through patronage networks, exclusionary economic and political policies that discriminated based on ethnicity created an exclusive, sense of citizenship, which is directly tied to the individual and their relationship to various patrons. However, the introduction of cash transfer programs, distributed based on need rather than patronage, has led to a gradual reconceptualization of citizenship towards one rooted in reciprocal rights and duties.
Between Silence and Resistance: Kurdish Women in Colonial Turkish Prison Diyarbakir Military Prison 1980-1984
Keywords: colonial sexual violence
gender
incarceration
Kurdish women
resistance
silencing

This study traces Kurdish women’s contestation of the carceral colonial Turkish State and challenges us to re-examine Kurdish women as historical subjects. It centres on the stories of Kurdish women who were incarcerated in the Diyarbakir Military Prison (DMP) beginning on September 12, 1980 following the military coup in Turkey. The DMP’s history is currently discursively shaped by male-dominated hegemonic narratives and archives from the colonial Turkish State and the Kurdish Movement itself. In this context, Kurdish women’s stories as political prisoners demand further scholarly exploration, and I argue that they must be prioritized as academic knowledge in their own right. This dissertation deals with the issues that have largely remained outside the concerns of existing scholarship on the Kurdish women in Turkey and the larger Middle East. The main analytical concerns of this study are incarceration, gender, politics of silencing and resistance. I draw on Kurdish women prisoner’s experiences from the DMP to demonstrate prisons as micro spaces of Turkish colonialism as well as spaces of resistance and knowledge production for the Kurdish Women’s Movement. Kurdish women reconstruct themselves within these historical, colonial, carceral spaces and reconstitute their own subjectivities through their understanding of what political incarceration meant for themselves, their families, and communities. I use feminist narrative inquiry and anti-colonial feminist framework as a methodological approach to trace the stages of Kurdish women’s voice to resist both internalized gendered shame and colonial sexual violence placed within the framework of the Kurdish women’s own history decade by decade: in the 1970s leftist activist women’s adherence to anti-colonial Kurdish organizations, the specific experiences of female social silencing coupled with State’s mechanisms in Kurdistan, followed by their prison activism and participation of hunger and death strikes as resistance in DMP. This study reveals hidden voices, stories and forgotten memories of Kurdish women political prisoners and the silencing mechanism that renders their voices unheard. Finally, by returning to the site of women’s resistance in the Kurdish women’s movement 40 years ago, this thesis will serve to expand the ideological and political theories that ground the current contemporary reality. Focusing on their strategies to resist what I call revolutionary gendered resistance in the DMP, this research highlights its impact on Kurdish women’s politics.
Lean In or Don’t Lean Out? Opt-Out Framing Attenuates Gender Differences in the Decision to Compete
Keywords: Choice Architecture
Competition
Gender
Intervention
Organizational Design

Research has documented a persistent gender gap in the upper echelons of organizations, which is in part attributed to gender differences in the propensity to compete and apply for promotions. In this dissertation, I argue that, rather than being the product of “dispositional” differences between men and women, this gender gap is due to the organizational contexts or organizational designs in which competitions take place. Most competitive selection processes (e.g., promotions) require self-nomination via an application (opt-in frame), which could disadvantage women. I propose that utilizing an opt-out frame for competitive selection processes will attenuate gender differences in potential candidates’ likelihood of applying. To test the theoretical underpinnings and practical implications of employing opt-out interventions to mitigate gender inequality, I develop a comprehensive set of laboratory and field-based experiments. The findings of these experiments provide compelling evidence that this gender difference can be eliminated by changing the default framing of a competitive task from one wherein applicants must actively choose to compete to one wherein applicants are automatically enrolled in competition, but can choose to opt out. Changing the default framing affects perceptions of prevailing social norms relating to gender and competition, as well as perceptions about the performance or ability threshold that is required in order to apply. This research contributes to theory by suggesting that gender differences in competition are not absolute, and by building on the conceptualization of inequality as a macro, system-level problem. On a practical level, the findings of this research have relevance for organizations aiming to close the gender gap in career advancement.