VictorJuiz/thesis huggingface dataset:
Free Expression Activism in a (Post)Modern World of Risk and Uncertainty

This thesis is about free expression activists and the central roles that risk and uncertainty play in their experiences. Today, activists who work on an array of free expression issues—including free speech, privacy, and press freedom—are driven by two principle predicaments. The first is the increasing pervasiveness of digital technologies, and the second is an aging liberalism deployed in increasingly conflicting fashions. Both of these predicaments are escalated by the post-9/11 preoccupation with national (in)security and the growing precarity of the neoliberal capitalist order in a world of economic and political globalization. Free expression activists work hard to foster conditions in which freedom can flourish (for themselves and others). But it is not only human rights discourse or other liberal idea(l)s that they appraise, confront, and grapple with on a day-to-day basis to conceive of their obstacles and advance their goals. Equally important are assessments and tools built on risk-based decision-making, discursive strategies that work to identify and harness risk and uncertainty, and other practices and ideologies through which risk and uncertainty are enacted. The goal is frequently to manage or minimize risk and uncertainty, but, by engaging them so strategically, free expression activists also end up accentuating them and giving them new, heightened meaning. Weaving through a series of free expression settings and subgroups, this thesis examines how activists experience and engage risk and uncertainty to achieve their own ends as they work at the intersection of liberalism, technology, and security. During their efforts, issues of personhood and statecraft are negotiated, bureaucratic encounters and network governance are navigated, and the intersubjective work of asking for and delivering help is performed. Moreover, complex contradictions that mark (post)modern life are explored, within which new kinds of power and resistance, as well as questions of morality, are being developed and taken up.

Advisor: Sidnell, Jack
Cody, Francis
Total Synthesis and Medicinal Chemistry of (+)-Prunustatin A and Analogues.

(+)-Prunustatin A is a natural product isolated in 2005 from a soil sample collected on the volcanic island of Kumajima in Okinawa, Japan and determined by Shin-ya to be a potent anticancer agent against hypoxic fibrosarcoma cells. The major challenges associated with the synthesis of (+)-prunustatin A are the 15-membered tetralactone ring formation, the formation of the requisite seco acid precursor and the β-keto-α-gem-dimethylester functionality, and the subsequent attachment of the 3-formamidosalicylate head group. A convergent approach toward the total synthesis of (+)-prunustatin A is described through the assembly of two key fragments and a macrolactonization. Shiina MNBA couplings were used for the formation of each of the four ester bonds in the tetralactone ring, including the key macrocyclization which was essential to minimize competing Thorpe-Ingold accelerated transesterification. Other key steps included an organoboron based prenylation using potassium prenyltrifluoroborate to install the gem-dimethyl group and a carbonyldiimidazole mediated coupling to form the salicylamide. In the course of the studies, a new method for preparation of the crucial salt was devised allowing for a shorter synthesis and easier reaction set up. Medicinal chemistry work on (+)-prunustatin A was focused on replacing the complex macrocycle with simple hydrophobic groups. Over 40 compounds were prepared and tested. Replacing the macrocycle with simple amines resulted in the complete loss of antitumor activity. Anticancer properties against TEX and HL60 leukemia cell lines were found in compounds containing a threonine or serine unit with various groups attached to it (longer hydrophobic chains performed better). Modifications on the aromatic headgroup were less well tolerated. Through this work, a new potent analogue that exhibited low micromolar activity (IC50: 0.4-0.8µM) against the aforementioned cell lines was identified, requiring only 5 steps for synthesis.

Keywords: Anticancer
Medicinal chemistry
Organoboron chemistry
(+)-prunustatin A
Total synthesis
Advisor: Batey, Robert A
PET Theranostics for Molecular Imaging and Radioimmunotherapy of Pancreatic Cancer

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of pancreatic cancer tumours. Panitumumab is an antibody that targets EGFR and can be radiolabeled for molecular imaging and radioimmunotherapy (RIT). This thesis aimed to develop a “theranostic” agent that could be used for both imaging and treatment of pancreatic tumours. The first study demonstrated the ability of 64Cu-panitumumab F(ab′)2 fragments to visualize patient-derived orthotopic pancreatic cancer xenograft mouse models with PET/CT imaging and showed the superiority of panitumumab F(abʹ)2 over IgG or Fab fragments. Next, studies were performed involving metal-chelating polymers (MCPs) to allow antibodies to carry up to 20-fold more chelation sites compared to antibodies directly derivatized with chelators for 64Cu-radiolabeling, thereby amplifying radiation delivered per antibody. This work demonstrated that the presence of pendant PEG chains on MCPs resulted in longer blood circulation times compared to MCPs without pendant PEG chains. The next study demonstrated that 64Cu-panitumumab F(ab′)2 was useful in RIT when combined with radiosensitizing agents in pancreatic cancer xenograft mouse models. Tumour regression was not achieved so the final investigation compared 64Cu and 177Lu-panitumumab F(abʹ)2, which have similar β-emission energies but 177Lu has double the abundance of β-emissions compared to 64Cu. 64Cu-RIT and 177Lu-RIT were compared to external γ-irradiation to determine their relative biological effectiveness (RBE) in four pancreatic cancer cell lines, with different EGFR overexpression and proliferation rates. This work demonstrated that the degree of EGFR overexpression did not predict responsiveness of cells to RIT with 64Cu- or 177Lu-RIT. Also, fast growing cells responded very well to 64Cu-RIT while slow growing cells responded extremely poorly, while proliferation rate did not correlate with response to 177Lu-RIT. In conclusion, 64Cu-panitumumab F(ab′)2 fragments can be useful in PET imaging of pancreatic cancer tumours and that 177Lu-panitumumab F(ab′)2 fragments are more appropriate for RIT.

Keywords: cellular dosimetry
EGFR
pancreatic cancer
panitumumab
radioimmunotherapy
Advisor: Reilly, Raymond M
Algorithmic Trading with Latent Models and Mean-Field Games

This thesis explores how agents should optimally trade in electronic markets when they account for latent factors and the optimal actions of other traders. It investigates the problem from the perspective of large-scale stochastic games with incomplete information and populations composed of heterogeneous agents, to which it provides closed form and model-agnostic solutions. The thesis contains two main parts. In the first part, we study the single agent optimal control problem when an agent has incomplete market information. Using the dynamic programming principle and filtration projection techniques we obtain closed-form formulae for the optimal trading strategy for a wide class of latent Markov models. We generalize this problem to an economy where the agent simultaneously trades multiple assets and tracks a stochastic benchmark. Using a novel method based on infinite-dimensional convex analysis we solve the agent’s optimization problem by representing it as the solution to a system of forward-backward stochastic differential equations. This allows both the extension to very general models for asset prices and implicitly provides the existence and uniqueness of solutions to the optimal control problem. In addition, we consider the practical implementation of these latent models and provide algorithms for the estimation of model parameters using expectation-maximization algorithm. In the second part, we consider the case of large populations of heterogeneous agents competing amongst one another on an exchange. We model these as stochastic games with partial and asymmetric information driven by latent semi-martingale price processes. By taking the limit as the population size tends to infinity, we obtain a mean-field game for which we can solve the Nash equilibrium in closed form by generalizing the convex analysis methods developed earlier. We further extend these models to incorporate disagreement amongst agents, represented by their beliefs on the probability measure driving asset prices. Although solutions to the extended model cannot be computed explicitly, we provide a least-square Monte-Carlo based algorithm to approximate the Nash equilibrium. In both cases, we show that the optimal solutions we obtain satisfy an ε-Nash equilibrium property in finite population games.

Keywords: Algorithmic Trading
Game Theory
Mathematical Finance
Mean-Field Games
Probability
Stochastic Control
Advisor: Jaimungal, Sebastian
St Antonin of Florence on Justice in Buying and Selling: Introduction, Critical Edition, and Translation

This dissertation presents an extensive introduction to the Summa of St Antonin (Antoninus, Antonino) of Florence and his teaching on justice in buying and selling. It also presents, for the first time, critical editions and English translations of three chapters of his Summa: 2.1.16 (On fraud), 3.8.1 (On merchants and artisans), and 3.8.2 (On the various kinds of contracts). St Antonin was a Dominican friar and archbishop of Florence from 1446 to 1459, and composed one of the most comprehensive medieval manuals of moral theology, his Summa. In his preaching and writing, Antonin sought to teach the merchants and artisans of Florence about the proper conduct of trade and exhorted them to practice virtue and moderation in the pursuit of profit. The first part of this dissertation is an introduction with four chapters. Chapter One provides a brief literature review on St Antonin and a biography. Chapter Two is a study of his Summa: its conception, textual witnesses, and process of composition. This chapter demonstrates that the manuscripts traditionally considered to be the originals are indeed the author’s autographs, and offers the most extensive analysis of these manuscripts yet produced. Chapter Three expounds the development of scholastic teaching on justice in buying and selling in the thirteenth-century faculties of canon law and theology. Chapter Four explains Antonin’s teaching: its social context in renaissance Florence; its content, sources, and method; and its purpose, namely, helping the clergy in their pastoral duties of preaching, hearing confessions, and resolving moral dilemmas. A postscript comments on Antonin’s place in the history of moral theology. The second part of the dissertation, the appendices, is the critical edition and English translation, preceded by an explanation of the edition and followed by tables illustrating the recensions of each chapter, as well as a description of Antonin’s handwriting.

Keywords: Antonino
Antoninus
canon law
justice
preaching
theology
Advisor: Armstrong, Lawrin
Late Gadolinium Hyperintensity (LGH) of Colorectal Liver Metastases (CRLM) on Magnetic Resonance Imaging (MRI)

Late gadolinium hyperintensity (LGH) of solid focal liver lesions on MRI with extracellular contrast agents is typically considered a “benign” finding seen most commonly with hemangiomas, but has also been observed with colorectal liver metastases (CRLM). In the first part of this thesis, we determined the prevalence of LGH in CRLM on MRI with extracellular contrast agents. In a retrospective cohort of 134 patients with 232 pathology-confirmed CRLMs, the prevalence of LGH in CLRMs was 47.8% (95% CI: 39.7%-56.0%). Some CRLMs demonstrate tumour fibrosis, which is associated with long-term survival. LGH with extracellular contrast agents in CRLMs may be due to leakage of contrast and progressive accumulation in the extracellular space of fibrotic tumours. In the second part of this thesis, we determined whether LGH is associated with tumour fibrosis and overall survival in patients with CRLM using extracellular contrast agents. In a retrospective cohort of 121 surgical patients who received preoperative MRI with extracellular contrast agents after chemotherapy, LGH was associated with tumour fibrosis (R=0.43, p

Keywords: colorectal cancer
fibrosis
gadolinium
liver
magnetic resonance imaging
neoplasm metastases
Advisor: Moody, Alan R
Milot, Laurent
Three-Dimensional Musculoaponeurotic Architecture of the Human Lower Limb and its Functional Implications

The musculoaponeurotic architecture of the human lower limb has not been previously investigated in three-dimension (3D) at the fiber bundle (FB) level. As musculoaponeurotic architecture is a primary determinant of muscle function, the lack of architectural data has limited our understanding of functional characteristics of lower limb musculature and the development of high-fidelity simulation and biomechanical models. The overall objective of this thesis is to capture the 3D musculoaponeurotic architecture of all of the lower limb muscles, and to use this data to elucidate functional capabilities of muscle groups, individual muscles, and/or intramuscular partitions. In the first study, 48,000 FBs and all of the tendinous/aponeurotic components of 59 lower limb muscles were digitized and modelled, as in situ, to construct an architecturally comprehensive 3D lower limb muscle model. A detailed architectural analysis of three lower limb muscles demonstrated that each had unique spatial arrangement and morphology of the musculoaponeurotic elements resulting in functionally relevant intramuscular partitioning. The second study captured the 3D musculoaponeurotic architecture of vastus medialis obliquus (VMO) and longus (VML) in 12 specimens. The comparison of architectural parameters of VMO and VML indicated that the two partitions have distinct functional characteristics. The more vertical line of action (LoA), greater excursion and force-generating capability of VML suggested that it contributes primarily to knee extension, whereas, VMO’s more horizontal LoA, suggested a role in medial patellar stabilization. The third study investigated and quantified the 3D musculoaponeurotic architecture of the great toe muscles, in 10 specimens, at the FB/aponeurosis level. Functional differences were elucidated through the comparison of the architectural parameters of the medial and lateral great toe muscles and their intramuscular partitions. The medial musculature was found to have similar force generating capability as the lateral musculature, suggesting that medial and lateral forces are balanced. In conclusion, the 3 studies captured high-resolution 3D architectural data, which enabled detailed morphologic and architectural analysis of the lower limb musculature not possible to date. This volumetric data can be used for the development of finite element models capable of higher fidelity lower limb muscle simulation than presently available.

Keywords: Anatomy
Architecture
Biomechanics
Human
Modelling
Skeletal muscle
Advisor: Agur, Anne MR
Intimate Partner Violence in South Asian University Students

Intimate Partner Violence (IPV) is a substantial problem affecting women of all social, economic, and cultural backgrounds. Although women worldwide are affected by IPV, research suggests that belief systems justifying violence against women or adherence to traditional gender roles may place some women at particularly high risk. Moreover, although women are exposed to IPV at high rates, many choose not to disclose to formal support (e.g., law enforcement) or informal supports (friends, family) due to numerous barriers. Experiences of disclosure are essential to understand since the response received after IPV disclosure is important to psychological functioning. The current study adopted an intersectional framework to examine the experience of IPV from the perspective of young, female South Asian students. Based on a mixed methods approach, the overall results indicated that women were frequently affected by psychological/emotional forms of IPV and that some of these forms of IPV were particularly meaningful within the South Asian culture. Similar to women of the majority culture, more than half of participants disclosed to informal supports while very few disclosed formally. A substantial barrier to disclosure were cultural norms about dating. Finally, while psychological health was qualitatively related to the experience of IPV, statistical analyses did not support a relationship between the response received after disclosure and psychological health.

Keywords: Dating violence
Disclosure
Feminist
Intimate Partner Violence
South Asian
University
Advisor: Stermac, Lana
Immune Mechanisms in Arterial Homeostasis and Disease

Immune cells contribute to numerous homeostatic and pathological tissue processes making them an attractive target for therapeutic intervention. Large arteries exemplify this paradigm as they naturally harbor immune cells within the arterial wall, accumulating during chronic inflammatory diseases such as atherosclerosis. Despite our advances in our understanding of these processes, the regulatory networks, ancestry and mechanisms that maintain and propagate arterial immune responses remain unknown. This dissertation aims to elucidate these concepts during homeostasis and during atherosclerosis. The first chapter investigates the molecular signature of tissue resident arterial macrophages, their developmental pathways, and key mechanism that ensure their homeostasis. We show through gene expression profiling and multiple fate mapping approaches that adventitial macrophages represent a unique macrophage population with both primitive and definitive hematopoietic origins. These cells are maintained by self-renewal instead of circulating monocytes in both the steady state and acute inflammation. The second chapter focuses on the role of master transcription factor c-Myb in the development of atherosclerotic disease. Through the use of animals that are hypomorphic for c-Myb or have cell specific c-Myb depletion we show that c-Myb exacerbates atherosclerosis. This occurs directly through its effects on B cell development, regulating survival of B cell progenitors, harmful B2 cells and IgM-producing antibody secreting cells at multiple tissues sites. Collectively this work adds to the current field of arterial biology and provides a further impetus to investigate the mechanisms that regulate the artery in the steady state and inflammation.

Keywords: Aorta
Atherosclerosis
Macrophage
Plasma Cell
Advisor: Robbins, Clinton
Physiology of the Swallow and the Impact of Thickened Liquids in Post-radiation Head and Neck Cancer Patients

There is an increasing prevalence of head and neck cancers (HNC) in Canada and the United States, with approximately 52,000 new cases every year, and approximately 9,500 deaths annually due to the disease in the United States alone. In Canada, there are approximately 220 new diagnoses of oropharyngeal cancer and an estimated 120 deaths resulting from this cancer type per annum. Patients with oropharynx cancers commonly are undergo radiation treatment for their disease, which has good results in terms of tumor control. While survival is improving, patients are left suffering from radiation-induced toxicities. Dysphagia (swallowing impairment) is one of the side effects that can become a long-term, pervasive issue. Individuals with dysphagia are at risk for aspiration (food/liquid entering into the airway). Aspiration is estimated to occur in 30-69% of HNC patients after radiation treatment (range of 1-12 months) and is often silent (i.e. with no overt symptoms). Thickened liquids are commonly used to reduce aspiration in the neurogenic dysphagia population but there is a gap in our knowledge with regards to the impact that viscosity and texture modification have on swallowing in the head and neck cancer population. The studies in this dissertation will examine the potential of thickened liquids to reduce aspiration in patients who present with unsafe swallowing onthin liquids after the completion of radiation treatment (post-3-6 months) for cancers focal to the oropharynx.

Keywords: Dysphagia
Head and Neck
Oncology
Radiation Therapy
Swallowing
Texture Modification
Advisor: Steele, Catriona M
Compressive Instabilities in Metal-coated Polymer Microtrusses

Lightweight structures directly contribute to the sustainability of aviation, as their use reduces the structural weight of aircraft which in turn reduces fuel burned during flight. One family of lightweight structures are metal-coated polymers. Hybrid polymer-nanometal microtrusses are a member of this family. These structures are fabricated by 3D printing complex truss-like structures out of polymer material, and electrodepositing nanocrystalline metal onto the polymer. Recent work has shown that buckling instabilities govern the strength of these systems. Hence this study focuses on modelling local shell buckling, one of the critical buckling mechanisms. In studying filled-shell buckling, hollow-shell buckling theory provides the framework for the behaviour of the shell as it undergoes buckling in a filled cylindrical shell. However, a model for the core must be realized. The Southwell stress model is used to develop an energy model of the core as it is subject to radial displacements, and the Timoshenko energy method is then utilized to determine the axial buckling load for a filled cylindrical shell. The models developed in this thesis include a fundamental model where the shell and core are fully adhered, a non-adhesion model where the shell and core are not adhered, a hollow-core model where the core is partially hollowed out along its axis, and an inelastic model where the shell behaviour is inelastic. These models are later verified through finite element analysis. Experiments on dogbone specimens also revealed some practical implications that must be considered when attempting to validate these theories. In addition, optimization for minimum mass design was carried out using the newly-developed models. The results of these studies indicate that while the new models are theoretically sound, there are still aspects of metal-coated polymer structures which bear investigating. Fine-tuning of the present models is warranted, which may include more complex curve fitting procedures for determining the model constants or the use of numerical techniques other than finite differences. In addition, the manufacturing processes for these structures must be improved prior to their use as primary structural elements in aerospace applications.

Advisor: Steeves, Craig A