VictorJuiz/thesis huggingface dataset:
Regulation of Mucosal T cell Activation and Inflammation by NLRC3 and Tritrichomonas muris
Keywords: Immunology
Inflammatory Bowel Disease
NLRC3
NOD-like Receptor
T cell
Tritrichomonas muris

The mucosal immune system in the gut is specialized to protect the host from infection by pathogenic microbes while maintaining tolerance towards the antigen-rich microbiota. T cells are a major component of the mucosal immune system that help to respond to pathogenic microbial invasion while maintaining a tolerogenic environment during times of homeostasis. These T cells can be regulated by genetically inherited factors as well as factors from the environment. Since defects in T cell function can contribute to the development of inflammatory bowel diseases, it has become increasingly important to understand how these factors are regulating T cell function. In this thesis we seek to explore how an extrinsic microbe, Tritrichomonas muris and an intrinsic factor, NLRC3, separately contribute to T cell function and disease regulation in various models of colitis.
Cognitive Correlates of Anterolateral Entorhinal Cortex Volume Differences in Older Adults
Keywords: Alzhiemer's disease
Anterolateral entorhinal cortex
Cognitive Decline
Eyetracking
Memory
Structural volumetry

Alzheimer’s disease pathology first appears in the medial temporal lobe (MTL): in particular, in the anterolateral region of the entorhinal cortex (alERC). However, the scientific community has only recently begun to appreciate the importance of the subdivision of the human entorhinal cortex, and as such, our understanding of the alERC’s cognitive roles and how it fits into models of MTL function remains limited. In this dissertation, I describe a series of studies inspired by findings from the animal literature, which shed light on the cognitive functions supported by the alERC. Using structural volumetry, I quantified the volumes of the alERC and other MTL regions in a group of ostensibly healthy older adults with varying degrees of cognitive decline. I compared participants’ structural differences to their performance on behavioral tasks that we hypothesized represented cognitive functions supported by the alERC. Specifically, I investigated how alERC structural differences were related to performance on the Montreal Cognitive Assessment (MoCA), a standard neuropsychological assessment used in the diagnosis of AD (Chapter 2), as well as eyetracking-based behavioral tasks assessing intra-item configural processing (Chapter 3) and object-in-place memory (Chapter 4), cognitive functions which the rodent literature suggest are supported by the alERC. I found that participants who scored below the MoCA threshold score (indicating possible AD) had smaller alERC volumes (Chapter 2), demonstrating that alERC volume is related to cognitive decline. Further, intra-item configural processing – regardless of an object’s novelty – was strongly predicted by alERC volume, but not by the volume of any other MTL subregion (Chapter 3). Finally, alERC (and parahippocampal cortex) volume was also related to object-in-place memory for items in everyday scenes, but no such relationship was found for object-trace memory (Chapter 4). Together, these studies suggest that the alERC may support aspects of the spatial processing of objects, advancing our understanding of the cognitive correlates of the alERC. More pragmatically, the alERC-specific tasks I developed may prove useful in early screening for AD and evaluating its progression.
The Prion Protein Controls Polysialylation of Neural Cell Adhesion Molecule 1 during Cellular Morphogenesis
Keywords: Neural cell adhesion molecule 1
polysialylation
Prion protein
ST8siaII
ZIP6

The cellular prion protein (PrPC) is one of the most studied mammalian proteins. Despite the ongoing efforts and the ubiquitous expression of PrPC in vertebrate cells, the main function of this protein has remained enigmatic to date. Several lines of evidence pointed towards the involvement of PrPC in the morphogenetic reprogramming underlying the epithelial-tomesenchymal transition (EMT). To address this, we applied CRISPR-Cas9 genome engineering technique to establish multiple PrPC knockout cell models (Chapter 2). The follow-up studies uncovered a critical role of PrPC in EMT and showed that PrPC controls the polysialic acid (polySia) modification of neural cell adhesion molecule 1 (NCAM1). Surprisingly, this effect of PrPC on NCAM1 polysialylation relies on a novel signaling loop that modulates expression of ST8SIA2, one of the two polysialyltransferase enzymes responsible for adding polySia on NCAM1 (Chapter 3). Intriguingly, a comparative analysis revealed that PrPC levels correlate directly or inversely with ST8SIA2 levels in different cell models. Deep global proteome analyses of multiple PrP-deficient models not only uncovered surprising cell model-specific proteome shifts but also showed robust changes in the levels of MARCKS and BASP protein families at the plasma membrane. Further investigation of their involvement in a biology that controls NCAM1 polysialylation revealed that reduced levels of MARCKSL1 also led to a significant reduction of polySia-modified NCAM1 (Chapter 4). Data from this study emphasize a iii thus far underappreciated coordinated biology of PrP and NCAM1. A close comparison of knockout phenotypes in mice is consistent with a model, whereby several of the known phenotypes in PrP-deficient mice might be explained by the contribution of PrPC to NCAM1 polysialylation. Attempts to validate this model and to assert its significance for determining if perturbed PrPC signaling contributes to toxicity in prion diseases are ongoing and have not been included in this thesis at this time.
Extending the Atlas of Variant Effects in Human Disease Genes
Keywords: Calmodulin
Deep Mutational Scanning
Sumoylation
Variants of Uncertain Significance

Although we now routinely sequence human genomes, we cannot yet confidently identify functional variants. Here a deep mutational scanning framework is developed that combines random codon-mutagenesis and multiplexed functional variation assays with computational imputation and regularization to yield exhaustive functional maps for human missense variants. The framework is applied to five proteins corresponding to seven human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), NCS1 (neuronal calcium sensor 1), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin). The resulting functional impact scores correspond to known protein features, and serve to confidently identify pathogenic variation.
Elucidating the Molecular Mechanisms Involved in Assembly/Folding and Targeting V-ATPase a-subunit Isoforms to their Functional Destinations
Keywords: ER-associated degradation
Membrane protein
N-glycosylation
Protein degradation
Trafficking
V-ATPases

Vacuolar H+-ATPases (V-ATPases) are proton pumps distributed across membranes of specialized cells and luminal compartments. V-ATPases in the plasma membrane of osteoclasts are responsible for acidifying the surface of bone, essential for bone resorption. V-ATPases in the plasma membrane of metastatic cells acidify the extracellular space to facilitate invasion. The V-ATPase a subunit has four isoforms (a1-a4) that localize to distinct compartments. In invasive cancer, plasma membrane expression of a3 and a4 are required for metastasis while a3 is specific for the plasma membrane of osteoclasts. Thus, both isoforms are potential therapeutic targets. Sequences of a isoforms reveal putative N-glycosylation sites within extracellular loop II (ELII). Upon PNGase F and Endo H treatment, all a isoforms showed faster mobility on SDS-PAGE indicating the presence of N-linked oligosaccharide. Using site-directed mutagenesis, I showed that deglycosylated a1â a4 had shorter half-lifes, more rapid proteasomal degradation, endoplasmic reticulum (ER) retention, defective Golgi trafficking, and an inability to associate with ER assembly factor, VMA21. In addition, deglycosylated a4 showed defective cell-surface expression and assembly. Cutis laxa type II, osteopetrosis and distal renal tubular acidosis (dRTA) result from mutations within the a2, a3 and a4 subunits, respectively. To further map critical domains essential for V-ATPase structure and function, I studied human disease-causing missense mutations that affect conserved residues of a isoforms, specifically: a2P405L, a4R449H and a4G820R. a4R449H and a2P405L were unstable and degraded by the proteasomal pathway. The data also indicated that a2-P405 is required for Golgi trafficking while a4-R449 is essential for ER exit and cell-surface expression. a4R449H shows increased association with the assembly factor, VMA21. Molecular modeling of a4 predicts a4G820R would interfere with proton translocation through the cytoplasmic half channel formed by the a subunit. This work enhances our knowledge of a isoforms structure and informs possible therapeutic interventions against cancer metastasis and lytic bone diseases.
The quantification of the online control of goal-directed movement using frequency domain analysis
Keywords: Frequency domain analysis
Online control
reaching

The field of motor control has devoted a lot of attention to the use of sensory information during movements for the maintenance of accuracy. This sensorimotor processing has been colloquially termed online control. Its accurate quantification and identification has posed a continual challenge to motor control researchers. Consequently, many measures of online control have been developed and have shaped the concurrent state of the field. Recent theories of online control have posited the existence of multiple distinct feedback processes. The current dissertation sought to gain insights into the multi-faceted nature of online control by evaluating the utility of frequency domain analyses as a tool for its quantification. Frequency domain analyses were hypothesized to be sensitive to the aforementioned distinct feedback processes given the assumption that they operate at unique timescales. Four experiments were conducted and evidence was obtained in favour of the utility of frequency domain analyses for the quantification of online control. Specifically, frequency domain analyses were found to be both one of the most sensitive measures to online control and the most robust measure to offline contamination. Thus frequency domain analyses represent an excellent choice for the evaluation of online control processes. Additionally, theoretical insights were attained through the sensitivity of frequency domain analyses to the contribution of two distinct processes contributing to reaching performance. The first was an iterative visuomotor process that influenced reaching performance at relatively stable rates. Notably, the specific rate of influence was found to be flexible based on the spatio-temporal requirements of reaching movements. Additionally, frequency domain analyses were found to be sensitive to a second, non-visual process. This process was promoted in the absence of online vision and likely represented the contribution of a peripheral proprioceptive process. Importantly, contemporary alternative methodologies for the quantification of online control were not sensitive to the unique contributions of this secondary process. Altogether, the current dissertation reaffirmed and expanded upon the multi-faceted nature of online feedback utilization and provided a novel approach to its quantification.
Transformative Learning in an Interculturally-Inclusive Online Community
Keywords: Action research
Community of practice
English as a foreign language
Japanese as a foreign language
Narrative approach
Telecollaboration

My dissertation addresses the question of how foreign language (FL) students’ perspectives and attitudes about their target language (TL), target culture (TC), first language (L1) and L1 culture changed through communicating with each other during an online exchange project. Specifically, the research focused on the personal narratives of ten FL learners who participated in an online project between an English language class at a Japanese university and a Japanese language class at a Canadian university. The objective was to examine perspectives and attitudes about the students’ experiences during the online exchange project. The literature review showed that telecollaborative language exchanges enhance language learning and intercultural knowledge. Through the concept of community of practice (CoP) (Wenger, 2014), language learners improve their skills and become empowered. This study used Wenger’s notion of CoP as a theoretical framework in the context of university FL classroom settings. A narrative approach captures students’ experiences during their online communication. The findings demonstrate that students gained confidence and increased their motivation for learning the TL while expanding their language skills and cultural knowledge. Some students showed transformative processes. In both Canada and Japan, the participants appreciated their partners and the community members for friendship, shared interests and learning support, and were able to overcome linguistic challenges during the online communication. However, the findings also suggest that Japanese and Canadian students perceived their online community a little differently. These differences seem to be caused by the notion that the learning process was situated in a local CoP. The study concludes by offering theoretical as well as pedagogical implications to suggest how FL classes can better support the telecollaborative language exchanges.
Great Sexpectations: How Implicit Theories of Sexuality Shape Sexual and Relationship Well-being
Keywords: destiny beliefs
expectations
growth beliefs
implicit theories
relationship satisfaction
sexual satisfaction

How do people believe they can best maintain sexual satisfaction in their romantic relationships? In the current research, I draw upon the literature on implicit theories of relationships to develop and validate a scale examining two types of lay beliefs about how sexual satisfaction can be maintained over time. Individuals high in sexual growth beliefs think that sexual satisfaction is attained from hard work and effort, whereas individuals high in sexual destiny beliefs think that sexual satisfaction is attained through finding a compatible sexual partner. Across six studies (two cross-sectional online studies, a 21-day daily experience study, two dyadic studies, and an experimental manipulation; N = 1,896), I find evidence that those higher in sexual growth beliefs experience higher relationship and sexual satisfaction, and have partners who are more satisfied. Conversely, the effects of sexual destiny beliefs on satisfaction are contingent upon signs of partner compatibility: When individuals high in sexual destiny beliefs experience greater sexual disagreements in their relationship, they experience lower relationship quality. These results are independent of general relationship implicit beliefs, providing evidence for the uniqueness of these two constructs and the importance of examining implicit beliefs in the domain of sexuality. Overall, these results provide novel evidence that individualsâ lay beliefs about maintaining sexual satisfaction are important for understanding the quality of their sex lives and relationships.
New Mathematical Tools in Reach Control Theory
Keywords: Affine systems
Constrained control
Feedback control
Reach control
Switched systems
Topological obstruction

Reach control theory is an approach to satisfying complex control objectives on a constrained state space. It relies on triangulating the state space into simplices, and devising a separate controller on each simplex to satisfy the control specifications. A fundamental element of reach control theory is the Reach Control Problem (RCP). The goal of the RCP is to drive system trajectories of an affine control system on a simplex to leave this simplex through a predetermined facet. This thesis discusses a number of issues pertaining to reach control theory and the RCP. Its central part is a discussion of the solvability of the RCP. We identify strong necessary conditions for the solvability of the RCP by affine feedback and continuous state feedback, and provide elegant characterizations of these conditions using methods from linear algebra and algebraic topology. Additionally, using the theory of positive systems, Z-matrices, and graph theory, we obtain several new interpretations of the currently known set of necessary and sufficient conditions for the solvability of the RCP by affine feedback. The thesis also provides a rigorous foundation for the notion of exiting a simplex through a facet, and discusses uniqueness and existence of trajectories in reach control with discontinuous feedback. Finally, building on previous results, the thesis includes novel applications of reach control theory to parallel parking and adaptive cruise control. These applications serve to motivate new directions of theoretical research in reach control.
Sexual Narcissism and Social Comparisons in the Domain of Sexuality
Keywords: Narcissism
Romantic Relationships
Sexuality
Social Comparisons

The current investigation shows that people in romantic relationships compare their sex lives to the sex lives of other people and that these comparisons influence sexual and relationship satisfaction. Specifically, I show that those who are high in sexual narcissism, people who have a grandiose sense of their sexual self, and a lack of empathy for their sexual partners (Widman McNulty, 2010), are more reactive than those who are lower in sexual narcissism to sexual comparisons to superior relationships because they feel that unfavourable sexual comparisons suggest that their partner is not good enough for them. In Study 1, I found that those high in sexual narcissism were more likely to recall downward sexual comparisons, which boosted their sexual and relationship satisfaction. In Study 2, I found that those high in sexual narcissism reported that they would be more bothered by upward sexual comparisons, which in turn predicted lower sexual and relationship satisfaction. In Studies 3 and 4, I showed that those high in sexual narcissism felt less sexual and relationship satisfaction after an upward sexual comparison, compared to those low in sexual narcissism. In Studies 5 and 6, I showed that sexual narcissists were more bothered by upward comparisons due to concerns about the partner being inferior. In Study 7, I found that those high in sexual narcissism make marginally more downward sexual comparisons, which predicts higher daily sexual and relationship satisfaction. Collectively, the current findings suggest that people do make comparisons in a variety of sexual domains in their day-to-day lives, and that these comparisons have predictable consequences for sexual and relationship satisfaction. Further, this research suggest that sexual narcissism is an important individual difference variable in determining how people make and respond to sexual comparisons in the context of their relationships.
ESSAYS IN ADVERTISING MESSAGES, MASS MEDIA, AND PRODUCT POSITIONING
Keywords: Advertising Message
Comparative Advertising
Consumer Search
Social-issue Advertising
Topic Model
Topological Data Analysis

In my dissertation, I apply emerging big data methodologies to measure the effects of advertising content and detect potential product segments. First, I explore whether advertising messages can change the topics reported in mass media. Specifically, I examine whether Dove’s real beauty campaign increased the incidence of real-beauty-related topics in newspapers. Using a topic model, I segment beauty-related topics and identify topics related to real beauty. The number of sentences labeled as real beauty topics increases during the campaign. While the Dove campaign’s significant impact on real beauty topics around the time of the campaign holds even in newspapers without Unilever ads, the impact is larger in newspapers containing Unilever ads. Overall, this evidence is consistent with both a mass media’s public service role and an advertiser pressure influencing mass media content. In my next study, joint work with Avi Goldfarb and Trevor Snider, I introduce a method for identifying potentially related products using topological data analysis (TDA). From both simulated and real consumer purchase data, I show that “loopy segments” in TDA can connect regionally separated local products through national products, while standard clustering methods such as hierarchical clustering cannot. Lastly, I test whether comparative advertising reposition rival brands closer together. Using Google Trends’ aggregate consumer search data, I analyze Samsung’s U.S. television comparative advertising campaign against Apple’s iPhone. I count co-occurrence of searches for brand pairs (e.g. Samsung Apple) and their brand-product attributes (e.g. Samsung screen, Apple Screen), to respectively map brand and product space. I find that advertised rival brands become closer together in both brand and product spaces but not significant in product space. My results suggest that a lower share brand may benefit from comparative advertising against a market leader by forcing itself to be more considered alongside a market leader when consumers search brands.
Palladium and Rhodium-Catalyzed Reactions for the Synthesis of γ, γ-Disubstituted Cyclohexenones and of some Trifluoromethylated Molecules
Keywords: arylation
boronic acids
fluorine
isomerization
palladium
rhodium

This thesis describes new applications of palladium and rhodium catalysis directed toward the synthesis of γ,γ-disubstituted cyclohexenones and of some trifluoromethylated molecules. The contents are divided in three chapters. Chapter 1 describes the development of a palladium-catalyzed α-arylation protocol applied to cyclic vinylogous esters to yield products that can be transformed in a one pot process to γ-alkyl, γ-aryl disubstituted cyclohexenones. The reaction was found to be generally high-yielding and displayed a broad scope with respect to both coupling partners. Chapter 2 describes a new class of redox isomerization of allylic alcohols that proceeds by desymmetrization of cyclohexa-2,5-dienols. The γ,γ-disubstituted cyclohexenone products were formed in high yield and the reaction was found to tolerate different functional groups. Mechanistic studies were performed and revealed some details about the course of the reaction, a formal 1,3-hydride shift. Chapter 3 contains two methods based on the palladium or rhodium-catalyzed addition of organoboron reagents to carbon-carbon or carbon-oxygen double bonds, applied to the synthesis of some trifluoromethylated molecules. In the first part, the palladium-catalyzed enantioselective addition of arylboroxines to trifluoromethylacetaldimines (or their N,O-acetals) is detailed. This process yields α-(trifluoromethyl)arylmethylamines which are useful building blocks in medicinal chemistry. The second part chronicles the development of a rhodium-catalyzed domino reaction for the enantioselective synthesis of a new class of small rings: (trifluoromethyl)cyclobutanols bearing an exocyclic double bond.