VictorJuiz/thesis huggingface dataset:
Targeting E1 Activating Enzymes through Small-Molecule Inhibition

The covalent attachment of proteins with ubiquitin and/or ubiquitin-like molecules (Ubls) is important for the maintenance of various critical biological pathways. Aberrant regulation of these protein labelling systems is often involved in the progression of diseases such as cancer and neurological disorders. To this end, targeting ubiquitin/Ubl labelling has emerged as attractive avenue in the discovery of novel drug candidates. Ubiquitin/Ubls are attached to protein substrates via a cascade of three enzymes: an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase. The main goal of this thesis is to target specific E1 enzymes with small molecule biological tools to investigate the role of these labelling systems in disease progression. First, a peptidomimetic strategy was used to target the E1 enzyme responsible for priming the Ubl SUMO, SAE. An Alanine-scan of peptides which mimic the C-terminus of SUMO proteins were used to understand which functional groups are necessary for disrupting SUMO-SAE interactions. This work concluded that mimicking the C-terminus of SUMO may not be sufficient to inhibit SAE enzymatic activity through a SUMO-competitive manner. When targeting UBA5, the E1 enzyme responsible for activating UFM1, unique structural features of this E1 were used to develop a UBA5-selective inhibitor. A thorough investigation of the mechanism by which the lead compound, 5C-Zn, elicits its activity revealed that Zn2+ is the active inhibitory species which acts through a time-dependent and irreversible mechanism. Finally, some of the Cu2+-metallated complexes from the preliminary library screen which were inactive against the human UBA5 were proven efficacious against UBA5 in Leishmanial donovani. Current research efforts now focus on determining whether the inhibitory activity is a result of the metal-coordinated complexes or Cu2+, as observed with 5C-Zn and Zn2+.

Keywords: E1 activating enzyme
inhibitor
ubiquitin
Advisor: Gunning, Patrick T
A Critical Analysis of Discourses on Knowledge and Absolute Authority in the Works of Ḥamīd al-Dīn Kirmānī and Mullā Ṣadrā Shīrāzī

The dissertation studies the mutual empowerment of epistemic and religio-political discourses in the Shīʿī contexts of the Fatimid Egypt and the Safavid Persia. Informed by the methodology of critical discourse analysis, the author investigates concepts, narratives, and arguments constituting several key texts that have contributed to the generation and development of philosophical Shiʿism that empowers the discourse of absolute authority of the imam and his representatives. The comparative study of the Ḥamīd al-Dīn Kirmānī and Mullā Ṣadrā Shīrāzī reveals the discursive continuation of the Shīʿī dynamics of knowledge and power. To demonstrate this, a large number of passages from primary texts in the original Arabic language are translated and closely analysed in terms of the concepts and narratives used. In analyzing the primary texts, the author particularly highlights the synthesis of different discourses including philosophical, Sufi, theological, and scriptural. Beginning with Kirmānī and Mullā Ṣadrā’s discourses on knowledge, the study highlights what their epistemic narratives have in common regarding the source and scope of human knowledge and to what extent they incorporate both Greek philosophy and Qurʾanic narratives of spiritual perfection.

Keywords: Hamid al-Din Kirmani
Ismailism
Mulla Sadra
Shia philsosophy
Advisor: Virani, Shafique N
REGENERATING REVOLUTION: Gender and Generation in the Sahrawi Struggle for Decolonisation

This dissertation investigates the forms of female labour that are sustaining and regenerating the political struggle for the decolonization of the Western Sahara. Since 1975, the Sahrawi national liberation movement—known as the POLISARIO Front—has been organizing itself, while in exile, into a form commensurable with the global model of the modern nation-state. In 1991, a UN mediated peace process inserted the Sahrawi struggle into what I describe as a colonial meantime. Women and youth—key targets of the POLISARIO Front’s empowerment policies—often stand for the movement’s revolutionary values as a whole. I argue that centering women’s labour into an account of revolution, nationalism and state-building reveals logics of long duree and models of female empowerment often overshadowed by the more “spectacular” and “heroic” expressions of Sahrawi women’s political action that feature prominently in dominant representations of Sahrawi nationalism. Differing significantly from globalised and modernist valorisations of women’s political agency, the model of female empowerment I highlight is one associated to the nomadic way of life that predates a Sahrawi project of revolutionary nationalism. I speak of a labour of “regeneration” rather than one of “reproduction” to foreground the political agency inherent to women’s daily work whilst also attending to intergenerational differences in political habitus. Enquiring into how Sahrawi women reckon with the contradictions produced by the conditions of a colonial meantime, I examine transformations in women’s labour of love, collective remembrance, hospitality, institutional participation, and practices of marriage/reproduction, to trace the inchoate ways in which Sahrawi women are contributing to multiply the possible futures of a revolutionary process initiated more than forty years ago.

Keywords: Decolonisation
Refugees
Revolution
Advisor: Muehlebach, Andrea
Novel Electrostatic Actuators with Applications

High-end smartphone cameras suffer from large size, high power consumption, and slow performance. These issues are mainly due to the poor performance of the voice coil motors (electromagnetic actuators) used to achieve autofocus (AF) and Optical Image Stabilization (OIS) features in these cameras. Due the superior performance of Micro-Electro-Mechanical-Systems (MEMS) electrostatic actuators over that of other actuation technologies in terms of achieving low power consumption and fast response, micro-electrostatic actuators are being pursued to achieve AF and OIS in smartphone cameras. The maximum mass load displaced by MEMS electrostatic actuators reported in the literature has been limited to 2 mg (corresponds to the mass of a single lens). However, the required mass load to be displaced in order to achieve AF and OIS is in the order of 62 mg mass which represents the mass of a typical lens barrel containing 5 lenses. In this thesis, a novel design of a MEMS piston-tube electrostatic actuator was developed to meet the actuation requirements for AF and OIS in smartphone cameras. The new design overcomes the limitations of the initial design of the piston-tube electrostatic actuator, previously developed by the author. These limitations include the generation of an insufficient out-of-plane translation stroke which is limited to only 24 µm and a low output force also limited to displacing only a 1 mg mass. Two versions of the new design were developed, fabricated, and tested. The latest version was specifically developed to meet the actuation requirements for AF and OIS in smartphone cameras. A new fabrication process, i.e. the MMDL fabrication process, was developed at the university of Toronto cleanrooms to meet the fabrication requirements for this version. The MMDL-fabricated actuator provides for 3 degrees of freedom motion and was able to translate and rotate a 62-mg lens barrel a stroke of 65.5 µm and an angle of rotation of ±0.4°, respectively. The actuator was integrated within a camera module to evaluate how well the actuator meets the requirements of the AF. The actuator achieved autofocus form 15 cm to infinity within 0.5 s, whereas high-end smartphone cameras achieve autofocus within 0.68 s.

Keywords: Autofocus
Electrostatic actuators
Large force
Large stroke
MEMS
Optical image stabilization
Advisor: Ben-Mrad, Ridha
Explanation in Chronicles of Western Europe in the Twelfth and Thirteenth Centuries

This dissertation examines the way historical writing was structured in Latin and Old French works of the late twelfth and early thirteenth centuries in Europe. Through comparative analysis of the Genesis section of Peter Comestor's Historia Scholastica with two later historical works, the Otia Imperialia of Gervase of Tilbury and the Histoire ancienne jusqu’à César, now attributed to Wauchier de Denain, this thesis argues that Comestor’s explanatory mechanisms influenced these later works in their treatment of supernatural events, their organization of historical narrative, and their descriptions of the natural world. Peter Comestor’s writing in the Historia Scholastica evinces three major goals: to preserve a continuous, seamless river of time, in which past and present are mutually intelligible and laid out in a clear order; to describe accurately a whole and seamless world, in which biblical events can be both mapped onto the known landscape of Comestor’s day and understood through the sciences of that time; and to create a seamless text, with no gaps or confusing passages. Both Wauchier de Denain and Gervase of Tilbury incorporate the content as well as the form of the Historia Scholastica, a fact which holds generic implications for these texts. The Historia’s structural adaptability made it useful to these two writers, and, I argue, may have been the cause of its popularity amongst other lay writers of history. Comestor’s work provided a template for connecting the meaning of stories and experiences with the meaning of history, and offered a means by which historical narratives could accommodate new connections to the present day. I argue that the structure of the Historia Scholastica, the material from which it drew its explanations, and its methods of explanation made it acceptable for later writers to imitate its structure and sources, and therefore made it possible and sensible for them to include material which we would not now categorize as proper to the historical genre: stories of contemporary experiences, folkloric material, and wonder tales.

Keywords: Gervase of Tilbury
Histoire ancienne jusqu’à César
Historia Scholastica
Otia Imperialia
Peter Comestor
Wauchier de Denain
Advisor: Goering, Joseph
Looking for Social Dance in Toronto's Black Population at Mid-century: A Historiography

The documentation of social dance within the lives of African-Canadians at mid-century is largely undocumented. This dissertation asks the question: Where did Toronto’s black population go to social dance during the 1950s and what is learned about African-Canadians via the lens of social dance? Through archival research I interrogate both sources and methodological approaches applied to social dance and/or African-Canadian historical work. I argue against reading African-Canadian documents and histories through dominant African-American historical narratives, proposing that historical and cultural overlaps are better understood in tandem with moments of departure into African-Canadian specificity. I look to Canadian contexts pertaining to social dance, legislation, trans-cultural exchange via black sleeping car porters on the train, leisure venues and music to inform close readings of photographs, newspapers and oral histories. This work emerges at the intersection of dance studies, Black Studies, performance studies, visual culture and cultural history and historiography. It proposes ways to contextualize doubt in archival research when verification is unavailable due to the systemic exclusion of African-Canadian and other marginalized bodies from Canada’s historical record. Through case studies my research looks at: photographs as a complex tool of equal rights advocacy; text-based documents that reveal the reinforcement of racist stereotypes through language about the black dancing body and repeated reports of discrimination in searches for “negro” and “dance” in mainstream newspapers; and oral histories as both invaluable and troubling documents that at once conceal and expose otherwise undocumented information pertaining to racism, social dance and African-Canadian heterogeneity. Despite shifting municipal, provincial and federal legislation in 1950s Toronto, leisure culture remained segregated. Alternative venues where African-Canadians gathered for social dancing include the Home Service Association, Universal Negro Improvement Association and University Settlement House (USH). While each of these spaces had unique mandates in terms of communities served, social dances at all three venues were attended by both black and non-black populations during the 1950s. These social dances are reported to have played otherwise inaccessible African-American blues and rock and roll music and resulted in repeated and ongoing interracial community gathering that was not otherwise reflected within mainstream culture. Social dance is proven to be a site of revelation about race, class, gender, generation and the African-Canadian population at mid-century.

Keywords: African-Canadian
Black Studies
Canadian History/Historiograpy
Dance Studies
Popular Culture
Social Dance
Advisor: Johnson, Stephen B
Family|Class: Race and Third-Order Immigration Policy Change in Post-War Canada

This dissertation addresses the scholarly debate about what happened to “race” as a core idea in immigrant selection policies during the shift – in Canada and elsewhere – from a nationalist-particularist policy paradigm to a liberal-universal one after World War II. The standard account of this “third-order” policy change is that race was replaced by universal human rights and equality as the main ideas according to which immigrant inclusion/exclusion is determined. Critics argue that race never truly stopped guiding immigrant selection frameworks and practices, and that racialized exclusion remains a core component of immigration policy and its implementation. I contribute to this debate by focusing on the micro-level dynamics of how the Canadian immigration bureaucracy negotiated the removal of explicitly racist clauses from immigration policy from 1952 and 1967. I adopt a discursive institutionalist framework that draws attention to how bureaucrats engage in interpretive practices that are shaped by – and shape – the repertoire of ideas present in the policymaking context. Using archival records, I examine how bureaucrats racialized potential immigrants in the policymaking context, how they linked this racialization (positive or negative) to the notion of immigrant admissibility, and whether/how racialization processes and their links to admissibility changed during the post-war era. My analysis yields three main findings. First, it shows that bureaucrats used the idea of race to construct differences between groups not just in terms of innate biological differences, but also in terms of class and status. Second, I reveal two mechanisms (“recasting” and “crossing individuals”) by which immigration bureaucrats changed the relative salience of these two components of the idea of race and show how these affected individual and group-level admissibility. Finally, I modify the punctuated equilibrium account of this post-war policy shift, which highlights bureaucratic resistance to exogenous pressures for change. I do this by showing how the substantive content of universalized entry categories in the 1967 Immigration Regulations emerged endogenously through the interpretive practices of immigration bureaucrats. The dissertation concludes by outlining the implications of these findings for scholarship on immigration, race and nation; immigration policy theory; and the role of states in boundary change processes.

Keywords: Class
Discursive institutionalism
Immigration Policy
Race
Status
Symbolic boundaries
Advisor: Korteweg, Anna
The HLD Framework for Complex Fluids with Polydisperse Nonionic Surfectants

Polydisperse ethoxylated nonionic surfactants are among the most common surfactants used in the formulation of a variety of products because of their mildness and low toxicity. To design complex fluids such as microemulsions and micelle-laden ionotropic hydrogels, it is important to understand the hydrophilic-lipophilic nature of these surfactants and their impact on the surfactant-oil-water (SOW) and surfactant-water (SW) phase behavior. In this work, this nature was determined via the characteristic curvature (Cc) parameter of the Hydrophilic-LipophilicDifference (HLD) framework. A simple and rapid method based on emulsion stability, was introduced for the determination of Cc of polydisperse surfactant samples. The measured values of Cc were consistent among different methodologies and technicians. The HLD framework, originally designed for SOW systems, was extended to SW systems with the objective of predicting the cloud point (CP) of ethoxylated surfactants. The HLD framework was successful in predicting the CP of pure ethoxylated surfactants, but failed to predict the CP of polydisperse surfactants. A liquid-liquid extraction method was then introduced to remove the more hydrophobic fraction of the polydisperse mixture, which allowed the surfactants to reach the CP expected for pure alkyl ethoxylates. The CP of the ethoxylated surfactants was then shown to dominate the behavior of surfactant-water-polymer (SWP) systems, where the polymer was gellan gum. Micelles of ethoxylated surfactants were laden in gellan gum systems that could produce strong gels in the presence of artificial tear fluid. These formulations allowed for an increased solubilization capacity of dexamethasone in the hydrogel, as well as an increase in the release time from 2 hours (no surfactant) to approximately 2 days (with surfactants). The extended drug release was then explained by the association of micelles to gellan gum repeating units.

Keywords: HLD
hydrogel
micelle-laden
nonionic
polydisperse
surfactant
Advisor: Acosta, Edgar
"Fragments of cloth, bits of cotton, lumps of earth:" Lists in American Literature, 1851-1956

This project traces literary catalogues through roughly a century of American literature and takes seriously the list as a distinct and rhetorically significant aesthetic category. While inventories and enumerations are typically meant to regulate and organize information, when housed within literature they behave quite differently. Literary lists can be overwhelming and boring; they can arrest narrative progression and ask us to pause for a moment of meticulous accounting. In the first chapter, I argue that Herman Melville’s Moby-Dick; or, The Whale leaves the reader awash in a world teeming with whale facts and figures. These “oceanic” lists, I assert, toggle somewhere between the metaphorical and the literal, playing at a scientific certainty that is ultimately left unfulfilled. Chapter Two reimagines Walt Whitman’s catalogues in “Song of Myself” as initiating a rhetorical oscillation between the singular and plural, a process that works to repopulate the cultural representation of America with subjects who have traditionally been excluded or marginalized. In Chapter Three I position Gertrude Stein’s Tender Buttons as a collection of everyday objects left suspended somewhere between utility and aesthetics, and in Chapter Four I re-envision William Faulkner as an author-carpenter who builds a six-sided narrative “coffin” with his rotating list of characters in As I Lay Dying. In Chapter Five, I argue that James Agee reaches for an ethical relation with human beings through obsessive catalogues of their material things in Let Us Now Praise Famous Men, and my concluding chapter argues that Allen Ginsberg’s “Howl” enacts what I call an “aesthetic unrest” through its insistent crowding and overwhelming amount of activity. Contrary to what some scholars identify as the list’s potentially dangerous cultural function, I argue that literary lists perform a kind of strange oscillation: a restless tension that sits unresolved and ultimately registers an ethical engagement with otherness itself. Because these lists are so fundamentally strange, I conclude, they encourage us to reconsider not only that which is familiar and comforting, but also the ideological grounds upon which those distinctions rest.

Keywords: Aesthetics
American Literature
Critical Theory
Ethics
Lists
Modernism
Advisor: Cobb, MIchael
Le marchand et l'érudit. L'écriture du voyage asiatique chez Jean-Baptiste Tavernier et Jean Thévenot

Cette thèse explore les modalités de représentation des différences culturelles dans les imprimés de Jean-Baptiste Tavernier et de Jean Thévenot, deux voyageurs français qui se rendent au Levant, en Perse et en Inde au milieu du XVIIe siècle. Notre étude compare deux expériences différentes du voyage – le voyage « commercial » et le voyage « érudit » –, suivant trois axes conceptuels : les représentations de l’espace, des manifestations corporelles et de l’altérité religieuse. Ce découpage du corpus principal est enrichi par des comparaisons ponctuelles avec un corpus secondaire contemporain. La réflexion proposée se déploie dans deux directions, textuelle et contextuelle. En nous inspirant du modèle analytique de Terence Cave, qui cible les aspects « troublés » des textes (Pré-histoires. Textes troublés au seuil de la modernité), nous avons privilégié les mécanismes d’écriture qui mettent à mal le postulat d’un témoignage purement référentiel. Parmi ces dispositifs, nous nous sommes concentrée sur les développements hypothétiques, les descriptions par la négative, les anecdotes héroïsantes, ou encore les prises de position ambivalentes qui révèlent l’instabilité de ces textes. Ce regard microscopique sur le fonctionnement de l’écriture du voyage permet de récupérer des nuances du texte qui échappent aux ouvrages de synthèse sur le genre viatique, et de reconstituer ainsi une certaine mobilité des attitudes et des réflexions sur l’altérité. Il permet également de déconstruire certains stéréotypes de la critique traditionnelle, portant sur les degrés d’ethnocentrisme des auteurs et sur le caractère prosaïque de leur témoignage. Les analyses rapprochées du corpus sont enchâssées dans une perspective historique plus large, qui tient compte non seulement de la doxa de l’époque, mais aussi du contexte de publication des récits et du rôle des divers rédacteurs, ainsi que de la complexité des rapports entre les milieux protestant et catholique durant la période qui précède la révocation de l’édit de Nantes. Cette étude s’appuie entre autres sur des textes rares ou inédits, édités ici pour la première fois (comme la version intégrale de la Défense du Sr. Chappuzeau, contre une Satire intitulée l’Esprit de Mr. Arnauld). Ces textes nourrissent notre réflexion et démontrent à leur tour que les écrits relatifs au voyage sont loin d’avoir épuisé leur lot de « singularitez ».

Keywords: Jean-Baptiste Tavernier
Jean ThĂŠvenot
LittĂŠrature de voyage
Voyageurs franรงais en Orient
XVIIe siĂ¨cle
Advisor: Holtz, GrĂŠgoire
Le Huenen, Roland