VictorJuiz/thesis huggingface dataset:
Arterial and Venous Identity during Angiogenesis in Health and Diabetes

Background: Vascular complications of diabetes are due in part to impaired angiogenesis. The extent to which these problems are due to disturbed identification of newly formed endothelial cells (EC) as ‘arterial’ or ‘venous’ (i.e. AV specification), recruitment of perivascular cells (PVC), or perturbed growth factor expression, had not been addressed. Methods Results: Using microvascular preparations from type-I diabetes (T1D) and non-diabetic animals transplanted into T1D and non-diabetic hosts, we show that mice T1D have impaired vessel AV specification, displaying ubiquitous expression of arterial marker ephrin-B2, loss of hierarchical organization, and reduced PVC coverage. Blockage of PVC recruitment in normoglycemic mice did not affect blood flow, but recapitulated the vascular immaturity of T1D, implicating PVCs in AV-specification. The latter occurred with downregulated Jagged1 and Notch3, key modulators of EC-PVC interactions. Co-cultures showed that PVCs induce arterial identity by increasing ephrin-B2, while decreasing venous marker eph-B4. This was antagonized by hyperglycemia or by inhibiting Jagged1 in EC. Vessel sprouting and consequent loss of AV identity was also dependent on hepatocyte growth factor (HGF) secreted from PVCs, with HGF levels decreased in T1D. Vessel anastomosis and implant perfusion was delayed in T1D,suggesting a role for HGF in inosculation. Finally, EC exposed to pulsatile stretch (mimicking pulsatile flow) upregulated platelet-derived growth factor-b (PDGFb), which was blunted by hyperglycemia. Importantly, microvessels from mice with T1D displayed normal PVC coverage, hierarchical organization and Jagged1/Notch3 expression after implantation into non-diabetic hosts, indicating no ‘metabolic memory’. Conclusion: We show that AV identity is impaired in T1D, due to abnormal PVC recruitment, dysregulated expression of HGF (by PVC) and PDGFb (by EC). These findings are associated with disordered Jagged1-Notch3 signaling, and lead to ineffective vascular connections with the host, which can be normalized in non-diabetic hosts.

Keywords: Arterial and venous identity
Diabetes
ECs/PVCs
HGF
notch signaling
PDGF
Advisor: Vasconcelos, Sara
Husain, Mansoor
Burlesque Natural Philosophers: Eighteenth-Century Satires of Science and Social Innovation

Abstract This dissertation examines the socio-political underpinnings of the satires about science that proliferated in British literature from 1660 to 1800. Most scholarship on the topic assumes that frequent literary assaults reflected a prevailing scepticism about science, and this assumption continues to prejudice analyses of satires like The Virtuoso (1676), Blazing World (1668), and the Memoirs of Martinus Scriblerus (pub.1741). However, science was widely embraced as a reliable mode of investigation, and people were generally enthusiastic about it. Why then are there so many farcical natural philosophers in eighteenth century literature and so few respectable ones? I argue that the satirical virtuoso served as a focal point for new forms of social conflict. His zeal for scientific innovation registered broader, often unacknowledged, anxieties about Englandâ s emerging cultural of innovation. Thus, burlesque natural philosophers, who strive to topple traditional hierarchies of knowledge, serve as proxies for the dynamic middle orders, who were seen to threaten traditional social hierarchies. The dissertation is composed of five case studies focusing on different moments of intersection between science and social hierarchies. The first study is of Margaret Cavendish, whose fantastical travelogue Blazing World and its companion treatise on Experimental Natural Philosophy (1668) articulate the perceived link between epistemic and political revolution in a manner that most eighteenth-century satires merely imply. Next I examine Dr. John Woodward, perpetual butt of the Scriblerian group, whose satires fashioned him as an embodiment of social ambition and cultural degeneration. I then discuss three scientific parodies by Henry Fielding and how they reflected the growing presence of science in popular culture. The fourth chapter is on the surprising prevalence of science in oriental tales, and how stories like Rasselas (1759) and Vathek (1786) used the imaginative east to reflect on prospective technological advances like manned flight and large-scale engineering projects. The final chapter, on Elizabeth Hamiltonâ s anti-Jacobin novel Memoirs of Modern Philosophers (1800), explores the paradox of late-century conservatives who embraced scientific and economic progress, but who continued to regard such progress as threatening traditional social structures.

Keywords: British
Eighteenth Century
Restoration
Satire
Science
Advisor: Keymer, Thomas
On the Effectiveness and Challenges of Electrosynthesis Strategies in Escherichia coli

Conventional bioprocesses that aim to convert CO2 to fuels and chemicals do so through a supply chain that begins with agricultural products such as corn, intermediaries like dextrose, and eventually produce chemicals by fermentation. However, it has long been desired that bioprocesses be established to convert CO2 point source emissions to chemicals. Fundamentally, this is a thermodynamics problem since the use of CO2 as a feedstock requires an efficient mechanism to deliver energy to produce chemicals. The focus of this work is to examine several strategies for microbial electrosynthesis, the delivery of electrical energy to microbial cell factories, for producing chemicals. The study encompasses four areas type of microbial electrosynthesis and the results are summarized here: 1) Experimental work was performed to evaluate the affect of neutral red mediated charge transfer in mutant strains of Escherichia coli for the purpose of producing succinic acid. The results of this task showed wild-type cells exhibited the greatest molar increase in succinate yield with an 89% increase while an ldhA deficient strain showed 40% increase. The lack of direct charge transfer was implicated as the cause since an electron balance was not able to account for an increase in succinate. 2) We explored the use of mediators such has formate that can be generated from carbon dioxide and renewable electricity as a carbon source for cell growth and chemical production. An auxotrophic strategy was employed to engineer formate assimilation, and growth rate on formate as a C1 donor for folate was determined to be 0.33 h-1. This was 78% of the wild-type strain. 3) We developed a framework for analyzing how metabolic pathways can be efficiently engineered into microbes to produce chemicals. This orthogonality framework showed ethylene glycol to be a highly promising substrate for electrosynthesis applications. 4) Finally, a bioprocess for the conversion of ethylene glycol to glycolic acid was characterized and its suitability to replace glucose as a feedstock was examined. The maximum glycolate titres for the best performing conditions reached 10.6 g/L. The highest substrate uptake rate for ethylene glycol was determined to be ca. 5 mmol/gDW-h.

Keywords: Escherichia coli
ethylene glycol
glycolic acid
metabolic engineering
orthogonality
Advisor: Mahadevan, Radhakrishnan
Representation in the Shadow of Colonialism: Conceptions of Political Representation in 19th and 20th Century India

The starting point of this dissertation is the persistent political underrepresentation of Muslims in Indian legislatures since independence, and how this impugns Indian democracyâ s claim to be egalitarian and inclusive. The study argues that specific institutional arrangements for enhancing democratic representation of marginalized groups must be understood in their historical context. Therefore, this dissertation examines the debates over political representation in colonial India, and the terms of settlement in the Constituent Assembly of India, where group representation rights were acknowledged for certain groups but not for religious minorities. Mapping these debates, this work illustrates how the political sociology underlying constituency definition shifted over time and generated the contemporary structure of political exclusion for Muslims. Further, the specific history of political representation in India reveals its use for both non-democratic (representation for ruling or governance) and democratic (representation for self-rule or self-governance) purposes. This dissertation argues that Indian thinkersâ ideas of political representation bear a dual relationship to colonial thinking about representation as a tool for control and governance â a duality that engendered possibilities for an alternative version of liberalism in India. However, rather than fully institutionalize available alternatives to standard liberal ideas of political representation, the Constituent Assembly replicated colonial strategies and mechanisms. Through the historical reconstruction of arguments for group representation, I offer a normative defense for remedial measures to the problem of underrepresentation of Muslims in India and to move away from the shadow of colonialism on matters of political representation.

Advisor: Williams, Melissa S.
Dinosaur Palaeoecology in the Late Cretaceous of Alberta: Quantitative Assessments Using Vertebrate Microfossil Bonebeds and Stable Isotope Analyses

The Belly River Group (BRG) of Alberta is one of the best-sampled Late Cretaceous terrestrial faunal assemblages in the world, providing a high-resolution biostratigraphic record of terrestrial vertebrate diversity, and has potential to be a model system for testing hypotheses of dinosaur palaeoecological dynamics. Vertebrate microfossil bonebeds (VMBs; assemblages of small bones and teeth concentrated together over a relatively short time and representative of community composition) offer an unparalleled dataset to better test these hypotheses by ameliorating problems of sample size, geography, and chronostratigraphic control that hamper many palaeoecological analyses. The first half of this thesis uses the largest VMB dataset yet assembled to test if trends in vertebrate diversity and community structure in the BRG are best explained as a response to environmental and sea-level change, and finds that while the vertebrate community as a whole was sensitive to these changes, the dinosaurs were not. This provides evidence against the long-held idea that dinosaur communities were sensitive to small-scale environmental gradients within a single depositional basin. The second half of this thesis tests hypotheses of dinosaur diet and niche partitioning using stable carbon and oxygen isotope analyses of species and guilds in a VMB assemblage. Results of these analyses refute the hypothesis that large diet-tissue fractionations explain enriched stable carbon values previously found in dinosaurs, as similarly enriched values are found in multiple sampled vertebrate groups, suggesting instead that they are related to changes in local isotopic baseline. These isotope data were then compared with a similar analytical sample from a modern analogue vertebrate community collected from Louisiana. Broad overlap exists in many of the species and guild distributions in both the extant and fossil systems, suggesting a lack of community-level saturation in resource use, less exclusionary control on niche occupation, and stronger selection for generalists rather than specialists. Overall, the results of this thesis suggest that greater care should be taken when making inferences into dinosaur community dynamics in the absence of thorough quantitative assessments and extant analogue data.

Keywords: Community Ecology
Cretaceous
Dinosaur
Palaeoecology
Paleontology
Stable Isotope
Advisor: Evans, David C
Cultural Constructions of Trauma and the Therapeutic Interventions of Caribbean Healing Traditions

The psychological literature indicates that integrating traditional healing practices into counselling and psychotherapy with Caribbean clients may address some of the mental health concerns of this population and the underutilization of mental health services. Traditional healing is often used in lieu of mental health services; however, the lack of knowledge of the precise therapeutic interventions and mechanisms of change that are key components to such integration limit its clinical utility. To address this gap in the literature, this study explored the specific ways in which Caribbean individuals conceptualize trauma and the therapeutic interventions of Caribbean healing traditions as a treatment modality. A constructivist grounded theory approach was implemented in the data collection and analysis. Ten adults of Caribbean heritage living in Toronto, who used the therapeutic interventions of Caribbean healing traditions, each participated in one semi-structured interview. Three overarching themes emerged from the data: experiencing trauma and suffering, explanations and meaning of trauma and suffering, and healing interventions. The study highlights the role of history and culture in shaping idioms of trauma, distress and healing, and contributes to both research and practice by offering a substantive framework for assessing, diagnosing and treating Caribbean clients, which may address the many challenges to mental health care for this population.

Keywords: Caribbean healing traditions
Counselling and psychotherapy
Cultural competence
Historical trauma
PTSD
Spirit possession
Advisor: Moodley, Roy
Accelerating Secure Computations Under Fully Homomorphic Encryption

Fully homomorphic encryption (FHE) systems enable computations on encrypted data without decrypting and without knowledge of the secret key. In this thesis, we describe an optimized RLWE-based and NTRU-based variants of the FHE system recently proposed by Gentry, Sahai and Waters (GSW). Although the GSW system was widely believed to be less efficient than its contemporaries due to the dimensionality of its ciphertext, we demonstrate quite the opposite behavior. We first highlight and carefully exploit the algebraic features of the system to achieve significant speedup over the state-of-the-art FHE implementations, namely the IBM homomorphic encryption library (HElib) and DARPA's SIPHER implementation. We introduce several optimizations on top of our HE implementation, and use the resulting scheme to construct numerous secure applications. We introduce the first high performance Homomorphic Processing Unit (HPU) hardware accelerator. A carefully crafted parallel GPU implementation of our RLWE scheme running on an NVIDIA GeForce GTX980 achieved a speedup factor of 89,700x compared to DARPA's SIPHER v01 baseline implementation. Our single-staged homomorphic processing unit (HPU) hardware accelerator achieved a speedup factor of 57x compared to our GPU implementation. Our NTRU scheme is mathematically 4x more efficient than our RLWE scheme. In total, our NTRU scheme running on one single-staged HPU unit managed to achieve a combined speedup factor of 2x10^7 compared to DARPA's SIPHER v01 baseline implementation, which is twice the performance target originally set by DARPA's PROCEED program to accelerate fully homomorphic encryption. An additional 4.47x speedup can be achieved by implementing a log(n)-staged HPU unit at the cost of 3x the die area. Finally, by exploiting the computational independence in our FHE schemes and applications, a speedup factor of 10^9 can be achieved by distributing independent computations on 50 single-staged HPU units.

Keywords: Cybersecurity
FHE
Fully Homomorphic Encryption
GPU Acceleration
Secure Search
Advisor: Gulak, Glenn
Hawayo Takata and the Circulatory Development of Reiki in the Twentieth Century North Pacific

Scholarly literature on religion in contemporary North America and Europe has taken Reiki, a form of spiritual healing, to be indicative of broader trends in the late twentieth and early twenty-first century. These works generally assume Reiki is either a form of American unorthodox medicine in Oriental trappings or a form of Japanese religious practice that has found a place in Western biomedical settings. This dissertation avoids such characterizations by foregrounding transnational exchange instead of national culture. It argues Reiki is best understood as a product of the twentieth century North Pacific (specifically Japan, Hawaii, and North America). It proposes an analytical framework of “circulatory development” to understand Reiki’s movement through transnational networks. Circulatory development describes how the movement of practices transforms both the practices (as they are adapted for new audiences) and the people who encounter them (by embedding them in new social and spiritual relationships). This dissertation also proposes a category of “spiritual medicine” for practices that transcend the assumed differentiation of religious and medical spheres. Usui Mikao (1865–1926) fashioned Reiki’s earliest forms from a mix of elements in 1920s Japan, including some with long local histories and some that had been recently imported from North America. Since the mid twentieth century, Reiki’s most prevalent forms have been reconfigurations of Usui’s practice adapted for audiences in Hawaii and North America by a second-generation Japanese American named Hawayo Takata (1900–1980). Using archival materials and oral history interviews, this dissertation analyzes how Takata creatively transformed Reiki practice from the 1930s through the 1970s. It focuses on the relation between her gendered racialization as a Japanese American woman, her development of spiritual capital in social networks, and shifts in the meanings assigned to Japanese religion in Territorial Hawaii and mainland North America. It concludes that Takata’s innovations to Reiki practice both accommodated and resisted elements of North American cultural hegemony by gradually introducing practices intended to: 1) professionalize Reiki as a practice of spiritual medicine; 2) transmit “Japanese” values to her students, and 3) establish a form of “particular universalism” that valorized Japan while promoting Reiki as a “universal” practice.

Keywords: circulation
Hawayo Takata
Reiki
spiritual healing
spirituality
spiritual networks
Advisor: Klassen, Pamela E.
For All Peoples and All Nations: Anglophone Literature and the Imaginative Work of International Law (1884-2017)

This thesis explores how Anglophone literature debated the rise of modern international law since the late nineteenth century, including the founding of the United Nations and the 1948 declaration of human rights. While international law has its origins in the early modern period, it was largely at the turn of the century, with the Berlin Conference, that it began taking shape as a colonial and then a postcolonial, global ethics. In this thesis, I lay claim to literature’s capacity to legislate by examining instances where Anglophone novelists—including Joseph Conrad, Bryher, Vladimir Nabokov, Chinua Achebe, and Chimamanda Ngozi Adichie—work through the promises and problems of international jurisprudence. More than a mere reflection of international law’s evolving theory and practice, the literature I treat registers the law’s presumptions and first principles while interrogating its capacity to follow through with its declarations. In spreading the law’s claims while also submitting them to the scrutiny of close reading, these novels are both advocates of and at times stubborn liabilities for international law’s normative worlds. Collectively, these Anglophone novelists scrutinize international law’s ability to shape the ways we come to know ourselves and one another as rights-bearing individuals, international actors, advocates, and activists. Recent work in the humanities has begun to address the ways in which international law is a set of interlocked narratives that claim to enshrine common sense when, in fact, they curate and confine modern ways of knowing, feeling, and belonging. By attending to issues that often go unacknowledged in the ordinary practices of international law—questions about subjectivity and self-fashioning, concerns about security and citizenship—I continue the work of examining international law’s epistemologies. In approaching literature as responsive to legal developments, and law as dependent on the narrative logic conventionally reserved for literature, I narrate the kinds of life and liberty that international law makes both conceivable and inconceivable, while at same time examining the literary contexts that continue to shape its apparent common sense.

Keywords: human right literature
international law
Advisor: Henderson, Greig
Novel Aspects of the Response to Cellular Stress and Intracellular Bacterial Pathogens

The cellular stress response represents an essential mechanism that enables cells to adapt to an array of environmental and physiological conditions. Given the importance of these adaptive responses, it comes as no surprise that dysregulation of the stress response has been strongly implicated in various diseases including infection, neurodegenerative diseases, and cancer. The findings presented in this thesis reveal novel aspects of the cellular response elicited by stress stimuli including nutrient starvation, proteotoxic stress and infection by intracellular bacterial pathogens. We first highlight that various components of the machinery responsible for mRNA splicing undergo dynamic reorganization into cytoplasmic granules known as U snRNA (U) bodies during metabolic stress and infection. The formation of U bodies during stress is accompanied by an overall decrease in splicing components, including the U snRNAs that are essential for mRNA splicing. Furthermore, we report global transcriptional reprogramming of a core group of stress-related genes in intestinal epithelial organoids in response to endoplasmic reticulum (ER) stress and nutrient starvation, including transcription factors, chemokines, and genes involved in inflammation. The landscape of alternative splicing (AS) was also strongly affected by cellular stress, and we report the existence of a conserved mechanism to regulate the expression of splicing and RNA processing genes that involves the coupling of AS and nonsense-mediated decay (NMD). Lastly, this thesis underscores the importance of stress response pathways in the maintenance of cellular homeostasis and survival by highlighting a novel role for the natural compound isoginkgetin as an inhibitor of the 26S proteasome. Disruption of protein homeostasis via isoginkgetin impairs the ability of cancer cells to mount stress responses and sensitizes various cancer cell types to apoptotic cell death upon nutrient starvation. Taken together, the results of this research will contribute to the overall understanding of the mechanisms underlying the cellular adaptation to stress and will aid in the development of novel therapeutics for diseases in which critical arms of the stress response are dysregulated.

Advisor: Girardin, Stephen E