VictorJuiz/thesis huggingface dataset:
The Development of Local-acting Biologics to Treat Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and progressive joint destruction. Anti-TNF biologics have been developed to treat RA and although effective in the majority of patients, they require repeated administration and systemically inhibit TNF. This systemic inhibition leads to systemic immune suppression and can result in side-effects including opportunistic infections, serious infections and malignancy. To address these limitations, I developed a novel, local-acting biologic known as TNF sticky trap. This biologic was shown capable of inhibiting TNF while sticking or localizing to the extracellular matrix (ECM) where it is produced or administered. Next, cell lines inducibly expressing this local-acting biologic were generated, characterized and evaluated for their therapeutic efficacy in an animal model of RA. A single injection of cells expressing TNF sticky trap was sufficient to reduce arthritis and this local-acting biologic was undetectable in the serum of treated animals. Lastly, to help advance the translation of RA cell therapies into the clinic, a cell safety mechanism was developed and characterized. The development of a safe cell therapy inducibly expressing local-acting biologics could avoid the limitations associated with systemic therapies and improve the current treatment of RA.

Keywords: Arthritis
Biologics
Cell Therapy
CIA
Local-acting
TNF
Advisor: Nagy, Andras
The Social Antecedents and Consequences of the Sense of Distributive Injustice

Roughly half of working adults in Canada and the United States report a sense of distributive injustice––that their earnings are unjustly too low. This evidence provides an impetus to document the antecedents and consequences of the sense of distributive injustice. More specifically, it encourages us to examine two fundamental questions in the study of distributive justice: (1) What do people think is just and why? (2) And, what are the consequences of the sense of injustice for individuals? Using population-based data, I address these questions through an interdisciplinary lens by integrating perspectives in the social psychology of distributive justice, the sociology of mental health, and occupational health psychology. I assess the first question by fusing ideas in distributive justice and the work-family interface. I argue that the conceptualization of work-related inputs can be elaborated by considering the intersection of work and family roles. Specifically, I propose a model that delineates how excessive job pressures––and the ensuing role blurring behavior and work-to-family conflict––shape the expectation for greater rewards. My findings provide an updated account of the nature of work contributions for contemporary workers that shape their ideas of what they should justly earn. The second part of the dissertation examines the consequences of underreward, focusing on the situational factors that function as moderators. In one study, I show that the relationship between underreward and job dissatisfaction is contingent on forms of security, such that the association is attenuated for those with high job and financial security, and for those employed in the public sector. The interpretation of the patterns for job security encourages the integration of the Job Demands-Resources Model and Maslow’s hierarchy of needs. In another study, I examine the ways in which two dimensions of SES––education and income––moderate the effects of perceived underreward on mental and physical health. I test two competing hypotheses––buffering-resource and status-disconfirmation––that delineate the moderating role of SES. Taken together, this dissertation draws upon and integrates diverse theoretical perspectives to identify new forms of work-related contributions that shape perceptions of a fair reward and the situational factors that modify reactions to underreward.

Keywords: Distributive justice
Mental health
Social psychology
Stress Process
Work-family interface
Advisor: Schieman, Scott
Relational Data Enrichment by Discovery and Transformation

In the context of data preparation for data science, we study the data enrichment problem, which is the challenge of augmenting a table with relevant data. We consider two enrichment paradigms: (1) data enrichment via discovery, and (2) data enrichment via transformation. In the first paradigm a table is enriched with relevant data discovered in data lakes. Specifically, we study table union search as the search problem of finding tables that can be unioned with a query table. We present a probabilistic solution for finding top-k unionable tables with a query table within massive data lakes. We show that our table union search outperforms in speed and accuracy existing algorithms for finding related tables and scales to provide efficient search over large open data lakes. We also consider the complementary problem of building a directory structure over a data lake. We define a data lake organization as a navigation structure (graph) containing nodes representing sets of attributes within a data lake. We present a new probabilistic model of how users navigate a data lake and propose an approximate algorithm for constructing the optimal directory structure. We show that the organizations constructed by this algorithm dramatically improve the expected probability of discovering tables over a baseline technique and linkage graphs. In the second paradigm, a table is enriched with new attributes (features) that are constructed by transforming the existing attributes in the table. We define the prediction-based feature engineering for classification as the problem of predicting the most effective feature to augment a table with. We show that we can enrich tables with new attributes that improve the performance of classification tasks. We also show that the prediction-based feature engineering technique outperforms other feature engineering approaches in effectiveness and response time.

Keywords: Data Discovery
Data Enrichment
Data Management
Data Science
Dataset Search
Feature Engineering
Advisor: Miller, Renée J.
On the Collective Intentionality of Epistemic Communities

In this dissertation, I propose a new social theory for identifying and studying the social bearers of belief and knowledge, i.e., epistemic communities. My main research questions are: What is an epistemic community? What kinds of epistemic communities actually exist, if any? How do we properly identify and study these communities? My thesis is that we can identify social entities and properly attribute beliefs to epistemic communities as one type of these social entities by identifying and analyzing the collective intentionality that underlies them. I begin my dissertation by discussing a key methodological debate in the social studies of science. Importantly, I point out that methods which approach communities as intellectually and culturally unified groups of researchers, rather than as networks exchanging knowledge, practices and materials, are reasonably criticized on ontological grounds: community, as a concept, emphasizes messy, possibly non-existent boundaries which tend to essentialize actual social entities. I suggest a solution to this ontological problem through an analysis of collective intentionality. In short, collective intentionality is a group’s capacity to share an orientation towards some object or objective. I criticize summative explanations of collective intentionality and those theories which defend the reducibility of group beliefs to individual bearers. I claim instead that a group can only have beliefs in a collective mode and as a plural subject. My new social theory thus proposes the notion of intentional community, defined as a group that shares an orientation towards some object or objective, as a properly identifiable group that can hold beliefs. I suggest that an appropriate application of my theory to instances of epistemic communities prioritizes establishing the presence of collective intentions in epistemic communities over uncovering the content of those intentions. Furthermore, I challenge most collective intentionality theorists’ need for common knowledge among members of an intentional community, on the grounds that it does not serve its theoretical purpose and is not clearly identifiable in practice.

Advisor: Baigrie, Brian
Characterizing the Human Ubiquitin Conjugating Enzymes

Ubiquitin is a small (76 amino acid) evolutionarily conserved protein that is covalently conjugated to lysine residues (or rarely N-terminal amines) on substrate polypeptides, to alter their half-life, localization or function. Ubiquitin itself also contains seven internal lysine residues, all of which can be modified by additional ubiquitin molecules to form extended ubiquitin “chains”. Monoubiquitylation or different types of ubiquitin chain linkages can confer very different biological outcomes to a protein target. The ubiquitin conjugation process is carried out via a three-step enzymatic cascade consisting of an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). More than 600 genes coding for predicted ubiquitin E3 ligases have been identified in the human genome, along with just 35 active E2 genes and two E1s. Importantly, the specific subset of E3s that interacts with each E2, and the specific biological functions of most of the E2 enzymes, have not been elucidated. To better understand E2 functions, I conducted a series of interactome and gene essentiality screens. Proximity-dependent biotinylation (BioID) was performed in Flp-In T-REx 293 cells to identify interacting partners for 31 different E2 proteins. 2296 high confidence protein-protein interactions were identified amongst 964 different polypeptides. To identify E2 genes (and other genes linked to protein homeostasis) essential for cell fitness, CRISPR/Cas9 dropout screens were also performed in HEK293 cells, along with two different lung cancer lines, NCI-H1975 and SW1573. Several different context-specific essential E2 genes (and many other genes linked to protein homeostasis) were identified in this screen, indicating that E2s may represent viable therapeutic targets. Finally, two common methods have been used to identify the types of ubiquitin linkages that can be generated by specific E2-E3 pairs: in vitro autoubiquitylation reactions using recombinant ubiquitin proteins bearing a single lysine-to-arginine mutation, or direct identification using mass spectrometry. We compared these two methods by characterizing the linkage specificity of 12 different E2-E3 combinations, and demonstrated that mass spectrometry-based methods yield far superior results. Together, my work has thus provided important biological context to a poorly understood component of the ubiquitin system, the E2 family.

Advisor: Raught, Brian
Explaining the Resultative Parameter

This thesis proposes an explanatory account for the fact that some, but not all languages exhibit adjectival resultatives. It does so by synthesizing a number of earlier proposals. From Snyder (1995, 2016), I adopt the proposal that the setting of the resultative parameter must be acquired indirectly, being inferred from the presence or absence of bare stem compounding in the primary linguistic data. From Kratzer (2005), I adopt a small clause analysis of resultatives and the proposal that Snyder’s parameter is related to inflectional features on adjectives. Finally, from Son and Svenonius (2008), I adopt the proposal that adjectival resultatives involve a single syntactic argument being shared by the primary and secondary predicates. These proposals, combined with minimalist assumptions, yield: (i) a structural analysis of resultatives, in which they are represented by a resP adjoined to a VP, with a DP argument undergoing sideward movement between them, and (ii) an analysis of the parameter, according to which languages generate adjectival resultatives only if their lexicon contains uninflected categorizing heads. I then show that, under Chomsky’s (2013, 2015) label theory, with some modifications, an adjectival resultative can be derived only if the result adjective is categorized by an uninflected adj head (e.g., {adj_∅ , √FLAT} ). This demonstration concludes the theoretical explanation of the resultative parameter. The remainder of the thesis addresses some consequences of the explanation. First I address the appearance that my theory seems to wrongly rule out copular clauses and depictives in, for example, French. I argue that this stems from our conception of Agree, and present a theory of postsyntactic Agree that gives the right empirical results. Next, I address the previously unrecognized generalization that sideward movement from adjuncts is always necessary when possible. Using Cinque’s (1996) analysis for ACC-ing clauses, I show that this can be explained by a novel theory of adjunction synthesizing the pair-merge (Chomsky 2004) and late adjunction (Stepanov 2001) theories. Finally, I discuss the semantics that follows from my syntactic analysis. Although the semantic analysis seems implausible, I present corroborating evidence in its favour and argue that is more plausible than the alternatives.

Keywords: generative
label theory
parameters
resultatives
Advisor: Cowper, Elizabeth
Geodesic Nets With Few Boundary Points

Geodesic nets on Riemannian manifolds form a natural class of stationary objects generalizing geodesics. Yet almost nothing is known about their classification or general properties even when the ambient Riemannian manifold is the Euclidean plane or the round 2-sphere. We survey some results and open questions (old and new) about geodesic nets on Riemannian manifolds. A particular focus will be put on the question if the number of inner vertices (balanced vertices) in a geodesic net can be bounded by the number of boundary points (unbalanced vertices) or the total imbalance. We prove that a geodesic net with three unbalanced vertices on a non-positively curved plane has at most one balanced vertex. We do not assume any a priori bound for the degree of unbalanced vertices. The result seems to be new even in the Euclidean case. We demonstrate by examples that the result is not true for metrics of positive curvature on the plane, and that there are no immediate generalizations of this result for geodesic nets with four unbalanced vertices which can have a significantly more complicated structure. In particular, an example of a geodesic net with four unbalanced vertices and sixteen balanced vertices that is not a union of simpler geodesic nets is constructed. The previously known irreducible geodesic nets with four unbalanced vertices have at most two balanced vertices. We provide a partial answer for a related question, namely a description of a new infinite family of geodesic nets on the Euclidean plane with 14 unbalanced vertices and arbitrarily many balanced vertices of degree greater or equal to three.

Keywords: curvature
differential geometry
geodesic nets
riemannian geometry
Advisor: Nabutovsky, Alexander
Overdetermined Systems of Equations, Newton Polyhedra, and Resultants

First part of this thesis devoted to developing Newton polyhedra theory for overdetermined systems of equations. Let A1, . . . , Ak be finite sets in Z n and let Y ⊂ (C ∗ ) n be an algebraic variety defined by a system of equations f1 = . . . = fk = 0, where f1, . . . , fk are Laurent polynomials with supports in A1, . . . , Ak. Assuming that f1, . . . , fk are sufficiently generic, the Newton polyhedron theory computes discrete invariants of Y in terms of the Newton polyhedra of f1, . . . , fk. It may appear that the generic system with fixed supports A1, . . . , Ak does not have any roots in (C ∗ ) n. In this case one is interested in the generic consistent system. We extend Newton polyhedra theory to this case and compute discrete invariants of generic non-empty zero sets. We proceed with study of overdetermined collections of linear series on algebraic varieties beyond (C ∗ ) n. Here, for an irreducible variety X, we take a finite dimensional subspaces, Ei ⊂ H0 (X,Li), of the space of regular sections of line bundles Li , so that the generic system s1 = . . . = sk = 0, with si ∈ Ei does not have any roots on X. We extend a number of the results from the case of (C ∗ ) n to this setting. The main objects of study in the second part of this thesis are ∆-resultants of an (n + 1)-tuple of Laurent polynomials. ∆-resultant is a generalization of the classical resultant of two polynomials in one variable. For an (n + 1)-tuple of Laurent polynomials with sufficiently generic Newton polyhedra we provide an algorithm for computing their ∆-resultant. Again, for a tuple with sufficiently generic Newton polyhedra we provide a relation between the product of f1 over roots of f2 = · · · = fn+1 = 0 in (C ∗ ) n and the product of f2 over roots of f1 = f3 = · · · = fn+1 = 0 in (C ∗ ) n and a signed version ii

Advisor: Khovanskii, Askold
The Influence of Biomass Burning on the Arctic Atmosphere

Evaluating the influence of biomass burning on the Arctic requires continuous and long-term measurements of the transported emissions. In this thesis, ground-based Fourier transform infrared (FTIR) solar-absorption spectroscopic measurements at the Polar Environment Atmospheric Research Laboratory (PEARL) in Eureka, Nunavut, Canada from 2006-2018 are used to retrieve the atmospheric abundance of the biomass burning species CO, HCN, C2H6, C2H2, CH3OH, H2CO, HCOOH and NH3 . The retrievals of NH3 from Eureka FTIR measurements are the first long-term ground-based measurements of NH3 in the high Arctic. Measurements of NH3, CO, HCN and C2H6 were simultaneously enhanced in July-August 2014 and attributed to the 2014 Northwest Territories wildfires. Enhancements were observed in FTIR measurements at Toronto, and due to the differences in traveltimes between the sites, an approximate 2-day lifetime of NH3 in a smoke plume was determined, allowing for NH3 to undergo long-range transport and therefore suggesting that boreal wildfires may be a considerable episodic NH3 source to the Arctic. The greatest enhancements of NH3, CO, HCN, and C2H6 were observed from FTIR measurements at Eureka (2006-2017) and Thule, Greenland (2006-2017) from 17-22 August 2017 and attributed to the 2017 British Columbia and Northwest Territories wild- fires. A GEOS-Chem simulation illustrated that these wildfires contributed to surface-layer NH3 enhancements in the Canadian Archipelago of 0.01-0.11 ppbv from 15-23 August 2017, 0.14-5.50 times the background due to local seabird-colony sources, further indicating that boreal wildfire NH3 is an important episodic source of NH3 in the summertime high Arctic in addition to the persistent seabird-colony source. Detection of wildfire pollution events was performed for Eureka FTIR measurements and nine other Northern high- and mid-latitude Network for the Detection of Atmospheric Composition Change (NDACC) FTIR sites from 2003-2018. Enhancements of CO were detected and correlated with simultaneous enhancements of the biomass burning tracers HCN and C2H6, providing a means of wildfire pollution detection. Source attribution of the detected events was performed using a GEOS-Chem tagged CO simulation. Boreal North America and boreal Asia were the largest contributors to anomalous enhancements at all sites, with a recent increase in the boreal North American contribution from 2013-2018.

Keywords: ammonnia
Arctic
FTIR
PEARL
spectroscopy
wildfires
Advisor: Strong, Kimberly
Concussions in Competitive Artistic Swimming: Investigating Incidence and Injury Context through a Community-based Approach

Artistic (synchronized) swimming is a fast-paced, predominantly female aesthetic sport on which there has been very little research. Despite origins in theatrical performance, the physical demands of artistic swimming have evolved significantly, subsequently increasing the potential for traumatic injury, including concussion. Sport-related concussion is a traumatic brain injury that can result in behavioural complaints, cognitive impairments, mood disturbance, and altered sleep. Despite findings that female athletes may experience a greater rate of concussion, more symptoms, and longer recovery than male athletes, females remain under-represented in sport concussion research. Sport-related concussion in artistic swimming has not yet been examined. The purpose of this research was to explore the incidence and injury context of sport-related concussion in youth artistic swimmers in Ontario within a community-based research setting. First, a retrospective study examined the injury context factors surrounding concussions sustained during artistic swimming. Second, a prospective study measured the incidence of concussion in this population over one season, and further explored the injury context of concussion. The incidence risk of concussion was 1.91%, and the clinical incidence was 1.91 per 100 athletes. The most frequent mechanism of injury was contact with another athlete, most commonly during pattern transitions and highlights. Concussions occurred most frequently in in-pool training between November and March, and in the deep-end of the pool. Valuable sport-specific concussion resources for the artistic swimming community were developed through collaboration with Ontario Artistic Swimming. One of these resources was an injury tracking program. A qualitative study examining coaches’ perceptions of the injury tracker provided valuable feedback for improvements. The important lessons learned from this partnership include the identification of contact between athletes in artistic swimming, findings of concussion incidence comparable to other girls’ sports, and description of the injury contexts associated with concussion in artistic swimming. Exploration of concussion in artistic swimming is warranted to protect the health and safety of these athletes, to expand the research on sport concussion in girls and women, and assist coaches and officials in understanding the nature of concussions in artistic swimming.

Keywords: artistic swimming
athletic injury
concussion
incidence
youth sport
Advisor: Mainwaring, Lynda M