VictorJuiz/thesis huggingface dataset:
Mouse Model of a Novel Molecular Subtype of Atrial Fibrillation: Physiologic Characterization and Therapeutic Drug Targeting
Keywords: arrhythmias
atrial fibrillation
electrophysiology
genetics

The mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, are not fully understood, hindering the development of novel drugs. Elucidating the genetic causes of familial forms of AF can provide significant mechanistic insights and reveal novel drug targets. Our research group studied a large family with AF and identified a single rare variant shared exclusively by affected individuals, a heterozygous missense mutation in the CaV3.2 T-type calcium channel (TTCC) gene, CACNA1H (p.R1823H). Electrophysiological studies revealed that this mutation increases CaV3.2 current density, an effect that could be reversed by selective blockade of the affected channel. These data identify CACNA1H as a novel gene associated with the development of AF, but the underlying mechanisms are unknown. Moreover, TTCCs, though known to regulate atrial automaticity, have never been implicated in the pathogenesis of AF. Using a knock-in (KI/+) mouse model expressing the murine ortholog of the human variant, p.R1828H-CaV3.2, this thesis demonstrates direct causation of AF by the mutation and implicates enhanced atrial triggered activity as the major underlying electrophysiological mechanism. KI/+ mice had frequently prolonged episodes of AF and significantly enhanced vulnerability to AF induction compared to wild-type (WT) littermates. Characterization of the novel mouse model in vivo and at the cellular level revealed electrophysiological functional abnormalities known to provoke triggered activity and AF, including an increased frequency of spontaneous atrial beats in ambulatory animals and a significant burden of DADs in isolated atrial myocytes. AF vulnerability in KI/+ mice appears to be the direct result of the primary electrophysiologic abnormality, as KI/+ mice had structurally normal hearts noted by the absence of excess fibrosis, and HRV analysis revealed no evidence of autonomic tone imbalance. Selective blockade of CaV3.2 channels suppressed the increased DADs seen in mutant atrial myocytes and abolished AF inducibility in vulnerable KI/+ mice, suggesting that the CaV3.2-R1828H variant is directly responsible for the AF phenotype of KI/+ mice. The successful suppression of AF vulnerability and DADs by selective CaV3.2 blockade suggests TTCC modulation may be a potential therapeutic strategy in the treatment of AF.
Machine Learning for Improved Weather and Climate Predictions
Keywords: adaptive bias correction
deep learning
statistical post-processing
subseasonal forecasting
weather and climate prediction
windows of forecasting opportunity

Numerical prediction models that simulate the complex and chaotic atmospheric system have successfully transformed the field of weather and climate prediction in recent decades. However, there are several real-world scenarios in which numerical models prove to be slow, uncertain or biased. These models are characterized by immense computational costs due to the large amounts of data they regularly process. This raises the question: how can we use machine learning to efficiently improve the accuracy of weather and climate predictions? In this thesis, we introduce novel algorithms for tackling the stubbornly challenging task of subseasonal forecasting.We start by exploring whether we can train neural networks to emulate the full dynamics of a numerical weather prediction (NWP) model and predict the global atmospheric flow in the medium-range. Creating such a forecast requires understanding complex atmospheric dynamics as well as the interplay between several variables across a range of scales. We show that neural networks can indeed perform this task, closely emulating the one performed by physical NWP models. We then use the task and dataset defined in this work, to establish the first benchmark for medium-range data-driven weather forecasting. An even more challenging forecasting task is sub-seasonal to seasonal climate prediction. While the accuracy of short-term forecasting is sustained by physics-based dynamical models, these models, due to their deterministic nature, suffer from a decrease in skill on subseasonal to seasonal timescales. We tackle this problem using a hybrid dynamical-learning approach and introduce an adaptive bias correction algorithm that outperforms both de-biased NWP models as well as state-of-the-art learning models. We conclude this thesis by discussing the future directions and challenges in data-driven weather and climate prediction, with the aim of identifying our approaches’ shortcomings and limiting assumptions. The studies presented in this thesis illustrate how large and varied data, an increase in computing resources, and advances in deep learning intersect, meet and collide to create a fertile playground for a promising field of research.
Bridging the Gap Between Artificial and Human Intelligence Using Chess as a Model System
Keywords: Chess
Computational Social Science
Deep Learning
Human Centric AI
Machine Learning
Reinforcement Learning

In the past half century Artificial Intelligence (AI) agents have grown to become embedded in modern life. Understanding why these AI agents make decisions has become increasingly difficult as they become more capable. These agents are components of larger sociotechnical systems making increasingly more significant decisions and are often doing so in collaboration with humans, for example, by providing evaluations to a judge or by making recommendations on the next movie to watch. As such, we need to build AI agents that are understandable to humans and that can understand humans with whom they interact. In this thesis we will present research using a model system, chess. Chess has a long history of use at the forefront of AI research, from the mechanical Turk, to Deep Blue and AlphaZero. Moreover, chess allows access to large and diverse datasets, powerful chess engines that can act as oracles, and chess can be considered benign, i.e., the potential negative consequences of its research are low, making it an ideal model system for AI research. These characteristics led to our first work on building a new style of AI chess engines, ones that attempt to mimic human play---instead of ones that achieve higher performance. These models, called Maia Chess, are able to predict the actions of a player at a given skill level with higher accuracy than any previous methods. Building on the methods for building human-like chess AI we will show how they can be individualized, increasing their accuracy by targeting a specific person. This individualization leads to the models better understanding the mistakes that player makes and incorporates their play style allowing for their identification from a set of many players. We will also present a method that generalized the identification techniques. First we formalize the task into a novel type of stylometry, behavioural stylometry - the task of identifying chess players based solely on their actions in game. We then demonstrate a novel deep learning method that allows us to identify players from a set of over 40,000 candidates without any model fine-tuning. These then lead to the final discussion of the implications of these models, specifically the ethical implications of building AI systems that imitate specific people. This work seeks to use the chess results as a starting point, and describe the implications of these models in the near future. To do this we define a new term mimetic models to describe models that imitate specific player. Then we discuss the ethical concerns that may arise from their use. This discussion has become more grounded in reality in the months since its first publication, some parts described as near future developments and concerns have become real.
Large-Scale Experimental Validation and Design of Resilient EBFs with Cast Steel Replaceable Modular Yielding Links
Keywords: Eccentrically Braced Frames
Energy Dissipative Fuses
Hybrid Simulation
Large-Scale Testing
Steel Casting
Steel Structures

Shear-critical replaceable links, which were proposed about a decade ago for eccentrically braced frames (EBFs), require stringent detailing efforts for their connections and web stiffeners. They are also susceptible to undesirable failure modes such as weld fracture, web fracture, lateral torsional buckling, and local buckling. This thesis is focused on the experimental validation of a new generation of yielding links, referred to as cast steel replaceable modular yielding links (CMLs). The proposed links rely on the freedom of geometry offered by steel casting to promote simultaneous yielding to achieve an improved ultra-low cycle fatigue life and prevent undesirable failure modes. In addition, CMLs eliminate detailing efforts, simplify the design and post-earthquake repair process, and promote modular construction in EBFs. In this study, the limitations of EBFs are discussed and the need for an improved yielding link in EBFs is highlighted. Two designs of CMLs are experimentally validated through eight component- and five system-level experiments and their response parameters are characterized. The CMLs demonstrated excellent performance reaching rotations of up to 0.21 radians for small to medium size links, and a rotation of 0.11 radians for the largest links. Following this, the response of two prototype EBFs with CMLs is evaluated under earthquake excitations using pseudo-dynamic hybrid simulations (PsDHSs). A framework for performing PsDHSs on EBFs is proposed where the response of the yielding link is captured in a single degree of freedom system. Using these experimental results, a numerical model for CMLs is developed. A comprehensive numerical study is then performed on EBF structures ranging from 2 to 12 stories. The results from the PsDHSs and the numerical studies demonstrated that the seismic response of EBFs is often accompanied by large residual deformations. Therefore, a low-cost system for mitigation of residual deformations in EBFs is developed and validated through PsDHSs. Recognizing that the response of CMLs is affected by axial loads, the effects of axial loads on the response of CMLs is critically studied next. The study is concluded by presenting a set of guidelines for the design of EBFs with CMLs and for performing qualification tests on CMLs.
Creativity on Demand: Cognition, Materiality, and Sociality in Improvisation
Keywords: Action
Cognition
Creativity
Culture

This dissertation examines the situated character of creativity via a qualitative analysis of improvisational theatre performances. Across these papers I demonstrate how creativity emerges out of the relations between actors, audiences, and material settings. Chapter two analyzes the cognitive processes through which improvisers generate new ideas during live performances. In this chapter I highlight limitations in contemporary sociological research using dual-process models, demonstrating how improvised interactions feature elements of order and disruption, how improvisers develop propensities in their reliance on automatic and deliberate cognition, and how creativity emerges in large part through automatic responses to the social and material contingencies of a live performance. Chapter three analyzes the role of the material environment in the creativity of improvisers. In this chapter I develop a novel account of how affordances are perceived and enacted, one that can be used to bridge the gap between cognition and materiality in cultural analysis. Chapter four analyzes the social-psychological skills employed by improvisers to tailor their creativity to live audiences. Specifically, I find that, although improvisation is an inherently uncertain process, improvisers are able to put on successful shows consistently through their ability to generate expressive enthusiasm (“work the room”) make inferences about the mental and emotional states of audiences (“read the room”), orient their performance style to the inferred preferences of audiences (“feed the room”), and make effective use of theatre space (“play to the room”). Chapters 2-4 of this dissertation are presented as stand-alone articles. While each paper has a distinct conceptual and analytical focus, taken together they establish creativity as a situated phenomenon.
Microbial Regulators of Immunoglobulin A and their Impact on Host-Microbiota Crosstalk
Keywords: B cells
Immunoglobulin A
Mucosal Immunology
SARS-CoV-2
Tritrichomonas musculis

The microbiota plays an integral role in the regulation of host immunoglobulin A (IgA) responses. How viral and protozoan exposures alter the microbiota-IgA axis remains unclear. In this thesis, I explore how two microbes influence IgA production and reactivity including: (1) Tritrichomonas musculis (T.mu), a murine commensal protist that colonizes the intestinal tract, and (2) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), an opportunistic human pathogen that initiates infection through the upper respiratory tract. I tested the hypothesis that T.mu colonization elevated IgA levels in a T-dependent (Td) manner as well as altered IgA reactivity against fecal bacteria and the neo-antigen - Ovalbumin (OVA). In addition, I tested the hypothesis that acute SARS-CoV-2 infection impacted anti-microbial IgA levels in the oral cavity.
Playing Queer and Performing Gender at the Turn of the Eighteenth Century: The Unconventional Life, Voice, and Body of Julie D’Aubigny Maupin
Keywords: Baroque
Early modern
Gender
Opera
Queer
Sexuality

The late seventeenth century in Western Europe is an intriguing period for queer historians: the imagined boundaries between genders, sexual orientations, and even biological sexes were considered far more permeable than we might expect of such a patriarchal society. In this study, I look to this era not to find a perfect reflection of my own queer non-binary identity, but to explore the culturally-contingent nature of all understandings of gender. At the centre of my research is seventeenth-century opera singer Julie d’Aubigny Maupin. Maupin was gender- non-conforming in her outward appearance, openly involved with lovers of all genders, and was an expert fencer and duellist. Simultaneously an outstanding exception to the conventions of gender in her day, and an example of the fluid possibilities of gender at the turn of the eighteenth century, Maupin serves as the case study through which I explore the ever-shifting perceptions of queer and gender-non-conforming people in this era. Through careful review of the few available sources, I reconstruct, as far as possible, an outline of Maupin’s life—and, due to the variable reliability of these sources, I note the many vagaries, contradictions, and impossibilities along the way. As I navigate this “speculative biography,” I rely on Valerie Traub’s concept of the unknowability of history, and am therefore careful to hold space for ambiguity, uncertainty, and all too often, an unsatisfiable curiosity. In subsequent chapters, I bring several aspects of Maupin’s life story, including her gender expression, sexuality, and status as a performer, into conversation with the surrounding social context of late seventeenth-century France, allowing me to offer insight into how Maupin’s contemporaries might have viewed her, as well as how her life relates to twenty-first century perspectives on gender. I then explore the many links between identity, character, and voice through an analysis of Maupin as a singer and performer, choosing four of Maupin’s most iconic roles and investigating them using interrelated lenses of historical context, performance practice, and my own embodied experience of singing excerpts from these operas. Lastly, I reflect on my personal connection with Maupin, and explore the philosophical implications of trying to retell a story as strange and unknowable as hers. Drawing on the Brechtian-inspired tradition of feminist theatre criticism set out by Elaine Aston, Sue-Ellen Case, and Gay Gibson Cima, I discuss the process of developing and writing the text for La Maupin, a solo cantata about Maupin’s life which I commissioned and premiered as a way to share her story with a wider audience. Throughout the dissertation, I also bring my research into dialogue with current views on gender-non-conforming people, including the latest research on the voice as a gendered phenomenon.
The Role of Child and Parental Factors on Parents' Feeding Practices in a Clinical Population of Children with Poor Growth
Keywords: child temperament
feeding beliefs
feeding practices
meant health
poor growth
public health policy

Failure to thrive (FTT) is a symptom of inadequate nutrition and growth. Parental feeding practices are important determinants in shaping weight and eating behaviors in children during a sensitive period of physical and cognitive development. The feeding interaction is a bidirectional relationship between the caregiver and the child and informed by different contextual factors such as family, parental and/or child characteristics. Responsive feeding has been found to promote children’s interest in feeding, as well as their awareness of hunger and satiety cues. This dissertation aims to explore parental beliefs and feeding practices in a clinical population of children with poor growth, as well as the contextual factors that influence parental feeding practices in this population. First, a systematic review and meta-analysis was conducted in order to synthesize the current literature examining association between parents’ stress and their feeding practices and/or styles, among parents of children ≤ 5 years old. Second, a clinical study with cross-sectional design was conducted among a clinical population of children with poor growth to examine the correlation between maternal concern about child weight or perceived feeding difficulties and feeding practices, and to investigate the role of child temperament and maternal mental health in a clinical population of children with poor growth. The findings from the two projects, showed that both general and parenting stress were associated with non-responsive feeding styles. Furthermore, higher maternal concern about child weight and perceived feeding difficulties were associated with less responsive feeding practices. Both child temperament and maternal mental health influenced the use of pressure feeding. Therefore, a review into current policies regarding parents’ mental health screening in a pediatric setting was conducted. The review suggests a lack of clear guidelines and recourse in order to support parents’ mental health screening in a pediatric setting. These findings provide a novel insight into the role of both the child and parents factors on parents’ beliefs and feeding practices. A better understanding of this relationship may provide pathways that could support and improve the clinical management of children with poor growth.
Stereoselective Difunctionalization of Alkenes and Alkynes: Synthesis of Heterocyclic Scaffolds
Keywords: Borylation
C-H functionalization
catalysis
cobalt
copper
heterocycles

Transition-metal catalyzed difunctionalization of alkenes and alkynes is utilized for the rapid construction of complex molecules by simultaneous addition of two functional groups across the unsaturation in one synthetic step. Within the various strategies that have been developed to functionalize π-systems, methods aimed at the synthesis of heterocyclic molecules continue to be explored as important targets in synthetic chemistry. The Lautens group has developed various transition-metal catalyzed domino cyclization methods for the synthesis of valuable carbo- and heterocyclic scaffolds. This thesis focuses on the development of base-metal catalyzed alkene/alkyne cyclization cascades to build different N-heterocyclic molecules.Chapter 1 describes two copper-catalyzed borylative cyclization strategies to synthesize γ-lactam scaffolds in a diastereoselective and enantioselective fashion. Using 1,1- or 1,2- disubstituted olefins, the reaction undergoes a boryl-cupration, and subsequent cyclization into a carbamoyl chloride motif to generate two different borylated lactam products. This strategy enables the stereoselective synthesis of these sp3 rich heterocycles, which are ubiquitous in nature, while serving as a complementary strategy to palladium-catalyzed domino reactions. Chapter 2 describes an asymmetric copper-catalyzed Kinugasa/Aldol cyclization reaction to form spirocyclic β-lactam scaffolds. Using alkyne-tethered ketones and nitrones, a highly diastero- and enantioselective β-lactam formation precedes a cyclization event to access products with three contiguous stereocenters. This methodology joins the few examples of Kinugasa/electrophilic addition reactions and serves as a facile route to valuable sp3 rich heterocyclic scaffolds. Chapter 3 describes an enantioselective cobalt-catalyzed enyne cyclization/indole C–H functionalization reaction. Methylene tethered pyrrolidine scaffolds are accessed by using 1,6-enynes, via a C–H functionalization at the C2 position of an indole. The reaction displays high atom-economy while generating products in a regio-, diastereo- and enantioselective fashion. This work highlights the potential of low-valent cobalt catalysis in C–H bond functionalization and enantioselective domino reactivity.
The Role of Stakeholders in Outreach Policy: A Case Study of Private and Public Universities in São Paulo, Brazil
Keywords: Brazil
Case Study
Extension
Public and Private Universities
Stakeholder Analysis
University Governance

Universities often develop community outreach practices to establish deep links with different sectors of society and to contribute to economic and social development. In Brazil, the development of federal extension policy was the direct result of national debates around the role of extension in the development of a democratic society after a military dictatorship. However, the lack of government evaluation, low and even diminishing funding, as well as difficulties to operationalize an extension definition resulted in inconsistent implementation of emerging policies. In this context, this thesis investigates how institutions develop their extension approach and how they manage different stakeholders. This study used a case study approach and qualitative methods to construct institutional cases representing the four categories of Brazilian universities: for-profit, confessional, public federal, and public state. Participant observation included institutional visits to three universities in São Paulo, a visit to a private higher education sector union, and virtual participation in extension events. Forty-six interviews were conducted with leaders of national extension forums and universities, administration, professors, and students. Document analysis included the collection and analysis of national and institutional extension policies, extension reports, and other documents collected through fieldwork. The data was analyzed using a combined stakeholder and multi-level governance framework. The stakeholder analysis framework was used to identify relevant stakeholders, provide a description of their roles and interests, and analyze how they interact with university and non-university actors. The multi-level governance framework was used to describe the different contexts that stakeholders operate in, organize the findings, and analyze stakeholder behaviour in relation to governance processes and structures. The findings contribute to the understanding of institutional and individual decision-making processes, practices, and behaviours that can affect change in policy and practice. Extension stakeholders navigate a complex system to exert influence on extension policy and the institutional approach by employing a diverse set of strategies, such as policy lobbying and implementing new institutional practices for the management of extension. Institutions respond to national policies and societal demands for a more engaged university, while asserting their values and traditions influenced by their institutional type, affiliation, and history.