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

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.

Keywords: Drama
Ethics
Shakespeare
Theatre
Advisor: Magnusson, Lynne
The Role of HSP90C in Chloroplast Maturation and Thylakoid Protein Transport

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.

Keywords: Chaperone
Chloroplast
Hsp90
Protein Homeostasis
Protein Translocation
Sec Translocon
Advisor: Zhao, Rongmin
What is She Hiding? Gender, Anti-blackness and the Strip-Searching of Black Women and Girls in Canada

This dissertation analyzes the legal and media archives of three cases of the strip-searching of Black women and girls in Canada. Through an extensive analysis of dominant legal and media discourses, this dissertation explores the ways in which Black women and girls are discursively constituted within the archives of the cases. The research examines the ways in which the strip- search encounter is a site of gendered and sexualized state violence that ultimately reveals the relation between the Canadian nation-state and Black women and girls. This study aims to explore but also intervene in Canada’s project of disavowing gendered anti-Black violence and asserts that this violence is not aberrational but instead, is foundational and constitutive of the Canadian nation-state. I situate these cases as part of a long and ongoing legacy of state violence and I illuminate the logics, narratives and discursive practices that naturalize the violence of the strip-search and obscure gendered anti-Black racism.

Advisor: Razack, Sherene
The Development of Assays for Detecting Proximal Phosphorylation and Covalent Modification of Proteins

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.

Keywords: Assay Development
Chemosensor
Covalent
Drug Discovery
Electrophilic Warhead
Proximal Phosphorylation
Advisor: Gunning, Patrick T.
Stability Enhancement of the Microgrid under High-depth of Penetration of Electronically-coupled Resources

This thesis introduces, develops, and evaluates an on-line (real-time) methodology to optimize (adjust) a set of pre-specified microgrid parameters, e.g., those of local controllers, to maintain stability of a microgrid subsequent to each discrete-event and a small-signal perturbation. A discrete-event changes the states and necessitates a new state-space formulation and a small-signal perturbation changes the operating point of the microgrid. The focus of this work is primarily on small-signal dynamics.A hierarchical supervisory control (SC) system, which provides power management for the microgrid, embeds the algorithms of the proposed method and enables parameter adjustment. The SC (i) identifies discrete-events and small-signal perturbations, (ii) activates and executes the corresponding algorithms accordingly, and (iii) commands the required parameters adjustment to the local controllers. The embedded tools within the SC are a Newton-based power-flow analysis, a modular state-space formulation, a cluster eigen analysis, a steepest-descent optimization, and a discrete-event supervisor. An off-grid microgrid and a multi-microgrid system, are used for the reported studies. Feasibility of the SC real-time algorithms is demonstrated based on their implementation on an FPGA hardware platform. The study results show that the proposed method can effectively enhance the microgrid stability subsequent to a set of single contingencies.

Advisor: Iravani, Reza
The Role of NLRX1 in Mitochondrial Stress

NOD-like receptors are a family of intracellular detectors of microbial and danger signals, that perform a range of functions regarding innate immunity. One member of this family, NLRX1, is the only NOD-like receptor to be localized to mitochondria. The findings in this thesis elucidate the true function of NLRX1, which is to facilitate mitophagy in response to mitochondrial stress. In situations where mitochondria are damaged beyond repair, they are engulfed and degraded through the process of mitophagy. Mitophagic clearance recycles molecular building blocks and prevents the accumulation of damaged mitochondria that can release dangerous molecules like reactive oxygen species and mitochondrial DNA and trigger apoptosis when not degraded. In Chapter 2, I investigate the functional interaction of NLRX1 with SARM1. Not only has SARM1 been implicated in apoptosis as a pro-death player, but it is also essential for the process of axonal degeneration. We show that NLRX1 modulates apoptosis through SARM1 and confirm the putative interaction and show that it is dependent on the leucine-rich repeat domain of NLRX1. We then demonstrate that NLRX1 is not involved in the axonal degeneration process that SARM1 oversees following axotomy, NGF withdrawal or vinblastine treatment. In Chapter 3, we identify a cytosolic pool of NLRX1 that is retained and stabilized outside of the mitochondria following mitochondrial stress. We then demonstrate that through interaction with an endoplasmic reticulum protein, RRBP1, NLRX1 facilitates mitophagy following depolarization and mitochondrial protein import stress. Mitophagy following import stress was not operating through the canonical pathway of PINK1-Parkin mitophagy, suggesting that the NLRX1-RRBP1 axis is independent of the canonical route. We then used exhaustive exercise to induce physiological mitophagy in mice and found that NLRX1-deficient animals had a reduced endurance capacity, accompanied by a reduction in mitophagy in the gastrocnemius muscle. Taken together, we propose that NLRX1 facilitates physiologically relevant mitophagy through RRBP1 to preserve mitochondrial and cellular homeostasis. This novel axis could be promoted in a therapeutic setting to prevent the buildup of toxic mitochondria that is commonly seen in many neurodegenerative diseases.

Advisor: Girardin, Stephen E
Mountain Industries and Votive Dedications in Roman Aquitania and Hispania

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.

Keywords: Aquitania
beekeeping
Hispania
mining
onomastics
silvopastoralism
Advisor: Bruun, Christer
The Trial of Socrates and the Idea of Athens

This dissertation proposes a new interpretation of Plato’s account of the trial of Socrates, a defining moment in the history of philosophy. Traditionally, Plato’s depiction of Socrates’ condemnation by his fellow citizens is thought to dramatize a perennial conflict between rational inquiry and uncritically received ideologies. I go beyond this traditional characterization and show that Plato’s account dramatizes a conflict at the level of ideology itself. I do this in a series of case studies that bring together the work of cultural historians and historians of philosophy. In the first chapter, I interpret Plato’s Crito in the light of the highly political genre of the Athenian funeral oration and show how, in this dialogue, Socrates’ decision to accept his death sentence exemplifies but also problematizes that genre’s vision of the ideal Athenian. In the second chapter, I argue that Socrates’ defense speech in Plato’s Apology uses the conventions of forensic oratory in a similarly subversive way, amplifying in the figure of Socrates an anxiety internal to Athenian civic identity. The third and final chapter situates my reading of the Apology and Crito within the broader context of Athenian political thought and among Plato’s other depictions of Socrates. Focusing on the Menexenus, Euthyphro, Laches, and Gorgias, it elucidates several ways that Plato uses the figure of Socrates to engage with the political mentality of his time and place. In sum, this dissertation provides new insights both into the image of Socrates received from Plato and into Plato’s political philosophy itself.

Advisor: Wohl, Victoria
Transcriptomic Characterization of Primary B Cell Acute Lymphoblastic Leukemia Identifies Novel Protein Biomarkers of High-risk Disease and Novel Mechanisms of L-asparaginase Resistance

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.

Keywords: Cancer
Diagnosis
Genomics
Immunology
Leukemia
RNA sequencing
Advisor: Guidos, Cynthia J
The Role of RNF168 and Novel Genetic Vulnerabilities in BRCA1/2-mutant Cancers

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.

Keywords: BRCA1/2
Breast Cancer
Cancer Therapy
DNA Damage Signaling Repair
Ovarian Cancer
R-loops
Advisor: Hakem, Razq
Reading the Theatre: A Lens-Based Method for Understanding Theatre Companies and their Facilities

This dissertation proposes a new way of reading and understanding theatre companies that operate their own theatre facilities (called venued theatre companies) operating in cities. This method utilizes a set of nine lenses that will dissect both a theatre company and its venue into parts that can be examined and discussed separately. These lenses are divided into three areas: Company, Building and Relationships. These areas are similarly divided into separate areas. The companies themselves are examined in terms of their History, Mandate and Operation. The theatre buildings/facilities they create and operate are examined in terms of Site, Stage, Front-of-House, and Infrastructure. A company’s relationships are considered in terms of those with its Audiences, and those with the City around it. These lenses are then applied to four not-for-profit theatre companies and their venues in Toronto: Theatre Passe Muraille at 16 Ryerson Avenue, Buddies in Bad Times at 12 Alexander Street, the Theatre Centre at 1115 Queen Street West, and Crow’s Theatre at 345 Carlaw Street. Each analysis delivers an extensive organizational and architectural history of the company and building that explains how these facilities came to be and work as they do. They will also outline the implications of choices made in theatre design and operation for the company, and for the theatre and urban ecologies around it. The dissertation continues with an analysis of what is learned from the four examples taken together, what can be understood about the construction and design of theatre facilities, and about the operations of venued theatre companies in the city of Toronto. It will conclude by discussing the implications of the COVID-19 pandemic for these companies and for theatre in general, and what it could mean for the future of theatre production in the city of Toronto.

Advisor: Johnson, Stephen