VictorJuiz/thesis huggingface dataset:
Borinic Acid-catalyzed Ring-opening of Epoxy Alcohols

Borinic acid catalysis has been used by our group to effect ring-opening and rearrangement reactions of 2,3-epoxy alcohols via reversible borinate ester formation. This work focuses on expanding the mode of borinic acid catalysis to the activation of 3,4-epoxy alcohols for regioselective ring-opening reactions with various nucleophiles. The current work is inspired by the methodology void for C3-selective ring-opening of homoallylic alcohol-derived epoxides, as literature precedence uses transition metal-based approaches that result in C4-selectivity. The prevalence of amino-, thiol-, and halodiol motifs in biologically important compounds, natural products, and synthetic intermediates for pharmaceutically pertinent molecules further encouraged research efforts in developing methodologies for the organoboron-catalyzed ring-opening reactions of epoxy alcohols.Chapter 1 discusses the development of a highly regioselective borinic acid-catalyzed methodology for ring-opening 3,4-epoxy alcohols with amines and thiols. A catalytic tethering mechanism that enables intramolecular delivery of the nucleophile to the epoxide is postulated to be responsible for the enhanced rate acceleration and regiocontrol observed. The resulting C3-ring-opening products from a broad substrate scope—including ones sterically biased to favour C4-selective outcomes—suggest the complementarity of this methodology to the current state-of-the-art C4-selective, transition metal-based protocols. Chapter 2 probes the mechanistic underpinnings of the catalytic cycle for the aminolysis of 3,4-epoxy alcohols. RPKA experiments using in situ reaction monitoring by NMR and ATR-IR spectroscopy are used to decipher the kinetic order dependences in catalyst and nucleophile. The derived rate law under catalyst inhibition by aniline agrees with results obtained using the VTNA method. Chapter 3 expands the borinic acid-catalyzed regioselective ring-opening methodology to halide nucleophiles, yielding C3-selective outcomes consistent with a boron-tethered mechanism. The regiocontrolled synthesis of halohydrin diols, from both 2,3- and 3,4-epoxy alcohols, presents a synthetically useful method for accessing these ubiquitous motifs in biologically relevant compounds. Chapter 4 discusses possible starting points for furthering the development of borinic acid catalysis relating to epoxy alcohol activation. Conducting more RPKA experiments can help elucidate the full catalytic cycle and shed insight on other promising nucleophiles that are compatible with the catalytic tethering mechanism exhibited by boron.

Advisor: Taylor, Mark S.
Ergativity on the Move

This thesis investigates changes associated with the ergative morphosyntactic alignment of the Inuit language. All these changes have been argued to signal an alignment shift from ergative to accusative, though none of them has ever been confirmed with detailed quantitative evidence. The most important change involves the rise of the antipassive construction in Inuktitut dialects at the expense of the ergative construction as the new default transitive construction (see Johns 1999, 2001a, 2001b, 2006, 2017; Spreng 2005; Carrier 2012, 2017; Yuan 2018). Other reported changes are 1) the elimination of overt transitive objects in the most innovative varieties, which would make the ergative construction a ‘marked’ transitive construction (see Johns 2017; Yuan 2018), and 2) the loss of the ergative case on transitive subjects in favor the absolutive case, which also marks intransitive subjects (see Tersis 2004; Langgård 2009; Carrier 2012). Using a variationist sociolinguistic approach to analyze data from North Baffin Inuktitut and a formal syntactic one to interpret the results, this study is the first to provide statistical evidence confirming that the ergative construction and the ergative case have been used progressively less and that they correlate with each other. I also posit that the general ongoing alignment change from ergative to accusative was first initiated by a neutralization in transitive subject number agreement, and that a series of changes has then successively triggered one another. Building on Brook (2018), I thus argue that these distinct changes constitute increasingly bigger envelopes of variation nested in one another and have in turn triggered one another after reaching a certain level of completion. One clear theoretical implication of these successive changes affecting distinct forms that display the traditional ergative alignment of the Inuit language is that ergativity is not a single concept but a macroset of many different properties (e.g., Dixon 1994; Johns 2000; Deal 2015a; Haig 2017).

Keywords: ergativity
Inuktitut
linguistic theory
syntax
variationist sociolinguistics
Advisor: Johns, Alana
Novel in vitro Microfluidic Platform for Studying Osteocyte Mechanobiology

Osteocytes are the major mechanosensing cells during bone remodeling. Current bone mechanotransduction research use macro-scale devices such as flow chambers; however in vitro microfluidic devices provide an optimal tool to better understand this biological process with its flexible design and high-throughput capabilities. Our recent work on co-culture platform has demonstrated the feasibility of building more complex microfluidic devices for osteocyte mechanotransduction studies. However, there still lacks a robust system where multi-physiological flow conditions are applied to bone cells during intercellular communication. I aim to improve the in vitro experimental platform for osteocyte mechanotransduction studies by 1) designing a novel multi-shear stress co-culture microfluidic device to study osteocyte intercellular communication; 2) testing the novel OCY454 osteocyte cell line to enable in vitro studies of osteocyte-osteoblast cross-talk; and 3) investigate magnetically actuated beams as a new method for in vitro fluid flow stimulation of osteocytes. I demonstrated that osteocytes seeded in the novel microfluidic device respond to different levels of fluid shear stress in each channel by varying amount of secreted RANKL. Furthermore, co-cultured osteoclast precursors had suppressed differentiation when next to osteocytes stimulated with high fluid shear stress. This microfluidic device can provide a new platform for researchers to further understand how mechanically stimulated osteocytes affect the bone remodelling process without complicated in vivo models. I also validated the response of OCY454 osteocytes to fluid shear stress, demonstrating changes in key indicators such as extracellular sclerostin level and intracellular calcium response, as well as capability to drive effector cell differentiation. This new cell line can help unlock further understanding of the role sclerostin plays in bone remodelling, and potentially give rise to novel pharmaceutical targets that can be used for treatment of bone diseases. Using novel magnetically actuated micro-beams, I experimented with a new method of generating localized fluid shear stress on osteocytes. This novel magnetic actuator can help us better understand how intercellular communication propagates within an osteocyte network when stimulated with localized shear stress. With development of new in vitro technical approaches to study osteocyte mechanotransduction, a better understanding of the bone remodeling process can be obtained.

Keywords: bone remodelling
intercellular signalling
microfluidic
osteoclast
osteocyte
Advisor: You, Lidan
Apolipoprotein A1 and High-density Lipoprotein as a Cargo and Regulator of Endothelial Transcytosis

Lipoproteins are circulating lipid carriers that regulate lipid homeostasis; low density lipoprotein (LDL) provides cholesterol, while high density lipoprotein (HDL) removes cholesterol from peripheral tissue. An imbalance of these processes leads to dyslipidemias and atherosclerosis, the accumulation of LDL in the arteries. To reach the target tissue, lipoproteins cross a protective monolayer of endothelial cells through transcytosis. Current understanding of transcytosis is limited and further complicated because endothelial cells vary depending on the tissue and vessel of origin. Indeed, brain endothelial cells are the most impermeant due to limited endocytic trafficking. In this dissertation, I investigate the relationship of HDL with the endothelium under physiological and pathophysiological states. Specifically, I aimed to elucidate the mechanism of HDL internalization in the brain endothelium in one study while determining the role of HDL in atherosclerosis in the other. In the brain endothelium, I found that HDL internalization is partially mediated by Scavenger receptor B1 (SR-B1) in a cholesterol-dependent, caveolae- and clathrin- independent manner. Furthermore, HDL internalization is independent of PDZK1 and the production of nitric oxide, which belong to the signaling pathway stimulated by the association of HDL with SR-B1. Together this suggests that HDL internalization is dependent on SR-B1 and cholesterol through brain- specific mechanisms. Given that atherosclerosis is also due to SR-B1-mediated transcytosis of LDL across coronary endothelial cells, I aimed to determine whether ApoA1, the protein found in HDL can prevent LDL transcytosis and how this is affected by the lipid state of ApoA1 as well as the natural mutant called Milano ApoA1. The Milano mutation results in half the plasma HDL levels, yet carriers do not develop atherosclerosis - the mechanism of which is not clear. I observed that ApoA1 can decrease LDL internalization and transcytosis by competition for SR-B1, while lipid-associated ApoA1 is more effective in inhibiting LDL internalization. The Milano protein is a slightly better inhibitor of LDL internalization but is comparable to wild-type ApoA1 in inhibiting LDL transcytosis and associating with SR-B1. Together this suggests that HDL is athero-protective by also inhibiting LDL transit across the endothelium, a process not affected by the Milano mutation.

Keywords: Apolipoprotein A1
Endothelium
High Density Lipoprotein
Internalization
Low Density Lipoprotein
Scavenger Receptor B1
Advisor: Fairn, Gregory D.
Lee, Warren L.
Touch Me, I’m Sick: Hysterical Intimacies | Sick Theories

This dissertation develops what I call a “sick theories” approach to the long history of labeling girls, women, and femmes – and their desires – as hysterical, sick, pathological, and in need of a cure. My approach builds on the insight that repressed trauma can lead to chronic illness, which was discovered in the early twentieth century with the emergence of the figure of the hysteric: a girl or woman experiencing inexplicable symptoms, from a persistent cough to full body seizures. Drawing on recent work in trauma studies, I offer a new lens to disability studies by reclaiming the figure of the hysteric, who has been largely neglected in this field. By examining a range of literary and cultural texts, I trace new connections between those who are living with trauma, chronic illness, and pathologized desire, and develop a language for imagining new forms of community and care, which I call “hysterical intimacies.”Each chapter builds on my sick theories approach, outlined in Chapter One, to analyze a different sick girl. Chapter Two looks at Jesmyn Ward’s novel Salvage the Bones to challenge the state’s narrative that the pregnant Black teen is part of an epidemic and reveal new dimensions of state sponsored anti-Black violence. In recognizing teen pregnancy as endemic new modes of community care, that cross species lines, open up. Chapter Three focuses on Marie Calloway’s what purpose did i serve in your life and Catherine Fatima’s Sludge Utopia, which depict what I call “ugly sex” – sex that both repulses you and gets you off. In embracing this ambivalence, these women refuse to have their desires pathologized. Chapter Four compares archival photographs of hysterics with Instagram selfies by authors Esmé Weijun Wang and Porochista Khakpour to demonstrate how chronically ill women reimagine communal forms of care that reject the neoliberal valorization of the individual. Ultimately, this dissertation shows how trauma and sickness enable new forms of relationality and community. These “hysterical intimacies” make it possible to show up in a world full of systemic violence with all of our trauma and sickness and imagine better worlds to come.

Advisor: Seitler, Dana
Public Shaming of Professional Athletes on Social Media

The overarching purpose of this dissertation was to explore the nature and extent of public shaming of professional athletes on social media in response to perceived legal, social, and sport-specific norm violations and the potential reasons that fans engage with athletes in this manner on social media. The methods employed were two-fold: for studies one and two, a qualitative content analysis of 7,700 fan comments on Facebook, Twitter, and Instagram directed at eleven male and female professional athletes from six different sports was conducted. To analyse these data, I implemented methodological pluralism by engaging in a semantic and subsequent latent thematic content analyses. For study three, guided by a narrative methodology, I conducted five semi-structured in-depth interviews with sport fans (three males, two females) who engaged regularly with professional athletes and teams on Twitter, Facebook, and Instagram. Findings cumulatively revealed that fans engage in public shaming of male and female professional athletes in response to the athletes’ perceived legal, social, and sport-specific violations. Public shaming on social media was evident with each athlete violation I examined, regardless of sport or experience level, and occurred across all platforms (Twitter, Facebook, and Instagram). Acts of shaming were illustrated by fans’ explicit withdrawals of support and descriptions of desired physical, psychosocial and career-related consequences for the athletes. In addition, there were undercurrents of gender and sexism observed across fans’ public shaming, which were exemplified through fans’ objectification of females, promotion of hyper-masculinity, and victim blaming. Fans proposed that public shaming acts occur in response to the threats that norm violations pose to fans’ sense of identification and belonging that have been cultivated through fandom and enhanced through the relationships perceived to be developed with athletes via social media. Specifically, fans suggested public shaming might be provoked when the integrity of fan-athlete relationships are challenged by legal, social, or sport-specific norm violations. Based on the collective findings, I explained the theoretical, methodological, and applied contributions of this dissertation to the existing literature, proposed ethical considerations for research of this nature, and discussed recommendations for future directions in this area of scholarship.

Keywords: athlete behaviour
fan-athlete relationship
gender
online behaviour
public shaming
social media
Advisor: Kerr, Gretchen
The Design of Playful and Intelligent Creative Tools

While ample research demonstrates the importance of concepts such as flow, playfulness and exploration for creative tasks, practical application of these principles leaves more to be desired, as evidenced by the prevalence of cumbersome creative interfaces. The goal of this thesis is to address the problem of designing playful, expressive and delightful creative interfaces for a number of concrete creative tasks, including interaction with color and 2D animation. To this end, I explore a number of approaches for establishing artist needs, develop digital representations that are amenable to both machine learning and user interaction, and design novel digital media that amplify, not stifle, creativity. This practical application of intelligence, including domain understanding and AI, and playfulness to the design of creative interfaces is meant to inspire future work in interaction design that adopts the same spirit.

Keywords: artificial intelligence
color
creativity support
human computer interaction
interface design
Advisor: Singh, Karan S
Fidler, Sanja
Two Essays on the Value of Marketing in the Digital Economy

Over the past three to four decades, explosive growth in data collection, storage, and processing has changed marketing practice substantially. For example, in business-to-business industries, advanced marketing analytics has supported salespeople’s decision-making by providing predictions based on new types of information. Furthermore, companies can reach consumers and ask their opinions more easily. The first essay of my dissertation quantifies the impact of the availability of such information on the marketing-sales interface. While marketing analytics intended to aid salesforce decision-making has developed rapidly, there is little empirical understanding of how the adoption of such marketing analytics may affect sales performance. Using data from a global business-to-business information technology company, we provide empirical evidence that the adoption of a new marketing analytics tool improved salespeople’s performance. By further exploring the outcomes by salespeople- and account-specific characteristics, we find that marketing analytics enabled high-performing salespeople to achieve greater sales from customers without recent transactions. In contrast, for low-performing salespeople, marketing analytics led them to winning more sales opportunities from accounts with recent transactions. Overall, marketing analytics empowers the high performers to reach a more balanced customer account portfolio and supports the low performers to seize the opportunities that might have been missed. Digitization has not only provided more information on customers but enhanced the means of communications between companies and their customers. The extant literature has explored positive behaviors that can occur after completing a survey, sometimes called the mere-measurement effect, but has neglected how the effect may depend on the valence of previous experience. In the second essay, we examine the impact of product performance on the mere-measurement effect using a unique natural experiment dataset from a securities brokerage company. Our results confirm mere-measurement effects in transaction intensity, transaction volume, and sales of other products. More importantly, the effects are greater for customers with negative pre-survey performance. The finding suggests that participation in satisfaction surveys leads to asymmetric positive effect. These results can help companies assess the return of resources invested in conducting surveys beyond the value of information and more accurately understand the relation between consumer behavior and marketing interventions.

Advisor: Goldfarb, Avi
Shi, Mengze
Numerical Simulation of the Stick-slip Instability for Laboratory Earthquakes using a Discrete Element Model

The fractal nature of earthquakes allows the study of their mechanisms in controlled laboratory environments. At the field scale, studies on earthquake nucleation mechanisms are dominated by two end-member theories––cascade triggering and preslip triggering. However, at the laboratory scale, very few studies have focused on the nucleation mechanism. This study aimed to discover the key factors that trigger stick-slip instability at the laboratory scale using numerical simulation.Numerical simulation provides a unique advantage in that it is capable of generating a large quantity of data at very little cost. Utilizing this advantage, a stick-slip experiment conducted by Goebel et al. was reproduced 27 times by employing a distinct element method (DEM) code, analogous to repeating the experiment on multiple Westerly granite samples. In particular, a dynamic-weakening pulse-slip model was built into the DEM framework, provided by Particle Flow Code (PFC), to promote rupture along the laboratory-scale fault. A data pipeline was constructed to collect, transform and analyze the numerical simulation data. New insights on the nucleation mechanism were derived from the data. The results rejected the hypothesis that mainshocks are directly caused by foreshocks. Instead, it was found that there was a strong correlation between a fault’s tendency to slip and the foreshock-induced acceleration of grain-scale normal and shear forces, which led to the idea that foreshocks indirectly prepare the nucleation zone to reach a state that allows a few acoustic emissions to cascade up into stick-slip instability. These results support the latest findings in the field, and could potentially resolve the disagreement surrounding the nucleation mechanism at the field scale.

Keywords: earthquake nucleation
machine learning
numerical simulation
Particle Flow Code (PFC)
Advisor: Young, R. Paul
Advances in Risk Parity Portfolio Optimization

Risk parity is an asset allocation strategy that seeks to equalize the risk contributions of the constituent assets in a portfolio. The resulting portfolio is fully diversified from a risk perspective. However, like other asset allocation strategies, risk parity is susceptible to estimation errors. Moreover, its mathematical formulation imposes some fundamental limitations. This thesis aims to modernize risk parity by addressing all of the aforementioned issues. We address the susceptibility to estimation errors through three different frameworks. First, we introduce a robust framework that quantifies estimation error and embeds this information during optimization to construct a robust risk parity portfolio. Our second framework takes a different approach, introducing robustness during the parameter estimation step. This is formulated as a game-theoretic minimax problem to make an optimal investment decision against the most adversarial estimate of our parameters. Our third framework improves the quality of our estimated parameters before optimization takes place. We posit that we can embed the cyclical information of financial markets directly into our estimates, resulting in risk parity portfolios aligned with the current market regime. The result is a Markov regime-switching factor model of asset returns from which we can naturally derive regime-dependent parameters for use during optimization. The final component of this thesis addresses the fundamental limitations of risk parity: its lack of accountability for the investor's risk and reward appetite and its prohibition of short sales. We propose a generalized risk parity framework where the investor's risk and reward appetite define our objective, while still enforcing a desirable degree of risk-based diversification. Moreover, we propose an algorithm that allows us to consider portfolios with short positions. Thus, our generalized framework addresses the fundamental limitations of risk parity while retaining the desirable property of risk-based diversification. The frameworks proposed in this thesis can be used independently or in tandem, depending on the investor's needs and goals. The unifying subject of this thesis is to advance risk parity by addressing its fundamental weaknesses. This is achieved by proposing different frameworks and algorithms, with the overarching property of preserving the interpretability and computational tractability of our solutions.

Keywords: Asset allocation
Convex optimization
Factor modelling
Portfolio optimization
Quantitative finance
Robust optimization
Advisor: Kwon, Roy H