VictorJuiz/thesis huggingface dataset:
From Structure to Function: Social and Cognitive Networks in Children Born Very Low Birth Weight
Keywords: cognition
functional connectivity
nutrition
preterm
very low birth weight
white matter

Infants born very low birth weight (VLBW, <1500 g) have an increased risk of social and cognitive impairments, which can affect their social and academic success at school. However, little is known about the functional and structural underpinnings of these impairments at preschool-age, an important transitional period in development, as well as the early modifiable predictors of outcome, such as postnatal nutrition. The present thesis used a multi-modal approach to investigate altered white matter microstructure and functional connectivity in five-year-old VLBW children. Using multi-shell diffusion imaging, studies 1 & 2 assessed white matter microstructure in VLBW compared to full-term (FT) children and associations with early nutrition (during postnatal days 9-29) and developmental outcome. Fractional anisotropy (FA), radial diffusivity (RD), neurite orientation dispersion index (ODI) and density index (NDI) were estimated using diffusion tensor and NODDI models. Using magnetoencephalography, social and cognitive networks were assessed during a resting-state (Study 3) and an emotional face processing task (Study 4). Studies 1 & 2 demonstrated disrupted white matter maturation in VLBW compared to FT children. These findings suggest that lower FA in VLBW children may be partly due to increases in axon dispersion, reflecting less coherent organization of axons. We also found that among the macronutrients studied, greater protein intake contributed most to the beneficial effect of nutrition, showing increases in FA and reductions in RD at preschool-age. Study 3 demonstrated increased resting-state functional connectivity in VLBW compared to FT children in the gamma (65-80 Hz) frequency band, anchored in frontal regions known to underlie social-cognitive functions. Further, significant associations between macronutrient/energy intakes with functional connectivity at preschool-age were found. Study 4 demonstrated that VLBW compared to FT children show atypical recruitment of emotional face processing networks in theta (4–7 Hz), specific to angry faces. This hypo-connected network involved key emotion face processing regions with links to inhibitory control. In conclusion, VLBW children showed alterations in structural and functional connectivity underlying social and cognitive functioning at preschool-age. Most importantly, our study relates these findings to early postnatal nutrition, demonstrating the long-term impacts of nutrition on preterm brain development.
Levi Decomposable Subalgebras of Classical Lie Algebras With Regular Simple Levi Factor
Keywords: Levi decomposition
Lie algebras
Representation theory

This thesis describes and characterizes a significant class of subalgebras of the classical Lie algebras, namely those which are Levi decomposable with regular and simple Levi factor, with select exceptions. Such subalgebras are entirely determined by their Levi factors and radicals. The possible Levi factors are well-established in the literature and so the contribution of this thesis is a characterization of the radicals. The radicals naturally decompose into nontrivial and trivial components. The nontrivial component is found to be fully classified by subsets of the parent root system and Weyl group. However, a classification of the trivial component requires solving the open problem of classifying solvable subalgebras of classical Lie algebras. Nonetheless, this thesis establishes a criterion on the trivial components for determining when two such subalgebras are conjugate. This thesis also briefly explores the ramifications of relaxing simplicity of the Levi factor to allow for semisimplicity.
Interracial Intimacies: Navigating Race and Culture in Heterosexual Racialized-white Relationships in Toronto
Keywords: Culture
Exogamy
Interracial Relationships
Mixed-Race Relationships
Race

The number of mixed-race couples in Canada, especially in metropolitan cities such as Toronto, is on a steadfast rise, yet there is limited culturally relevant research and literature on interracial unions. This study was conducted in response to the critical need for Canadian-specific research on this demographic, since there is an over-reliance on antiquated, problem-focused and United States-based research to inform the field of counselling and psychotherapy in Canada. The present study aimed to address this paucity by asking the question: what are the lived experiences of heterosexual, Racialized-White mixed-race couples in Toronto with regards to issues of race and culture? A constructivist grounded theory methodology explored the lived experiences of 12 heterosexual Racialized-White couples in Toronto and the Greater Toronto Area (GTA). Four key themes emerged from the findings – lived experiences of race/culture prior to mixed-race relationships; lived experiences of race/culture in mixed-race relationships; critical reflections on lived experiences: negotiating differences, racism and privilege, and being in ‘the middle’ of two races and cultures; and lived experiences beyond race/culture. The themes illustrated the multifaceted, vastly diverse and dynamic experiences and processes evident in these unions. This research further postulated that the experiences of interracial couples cannot be fully ascertained without a critical consideration within the context of Canadian colonialism, White supremacy, heteropatriarchy and endogamous discourse. A mid-level theory arose from this study, revealing the multilayered influences on and experiences of heterosexual interracial couples. Implications for education, research and counselling and psychotherapy are addressed, including contributions to intercultural counselling competencies and decolonial pedagogy for counselling psychology programs. Key Words and Phrases: Mixed-Race Relationships, Racialized-White, Race, Culture, Canada
Teacher, Talk, and Technology: Exploring Teaching and Learning in Grade 4 Mathematics
Keywords: Cross-curricular connections
Grade 4 Mathematics pedagogy
Roles for technology
Sociocultural theory
STEAM/SS
Technology integration

This doctoral dissertation sought to explore teachers’ experiences and challenges as they learn to use technology to support their students’ mathematics learning. The purpose of this study was to identify good, efficient, innovative teaching practices and strategies when technology is implemented and integrated in Grade 4 mathematics. The data for these cases were collected through the observation and interviews with two Grade 4 teachers. The diverse levels and quality of the communication, collaboration, cooperation, cross-curricular connections, and curriculum development emerged during their mathematics sessions with their students. The current research study revolves around these two Grade 4 teachers’ pedagogical practices, and conceptions of technology adoption and integration in their mathematics teaching practice, while evaluating how the technology was implemented and integrated into mathematics teaching and learning activities to enhance their students’ mathematics conceptual understanding. The qualitative study also explores the teachers’ experiences and perceptions concerning technology as a tool that mediates learning and discourse in their Mathematics instructional sessions. Teachers, their students, and their peers are continuously negotiating and navigating the pedagogical spaces that promote and enhance mathematics learning and interactions across cross curricular subject content, communication, and collaboration. The following are key factors, based on the findings of this study, that can contribute to the effective implementation of technology to enhance mathematical discourse: A willingness of teachers to improve their practice in the area of technology integration, the technology-related learning tasks need to be developmentally appropriate, and teachers need to be able to successfully identify, acknowledge, and respect how each student learns with technology.
Episodic Control: The Role of Memory in Decision Making
Keywords: Episodic Memory
Forgetting
Neural Networks
Reinforcement Learning

Reinforcement learning (RL) is an area of computer science concerned with trial-and-error learning of optimal behaviour. As such, RL can offer a normative framework for understanding learning in animals. However, some aspects of animal behaviour are not well accounted for by traditional RL solution methods. In particular, biological brains are able to learn and relearn quickly, flexibly using memory for specific events (i.e. episodic memory, EM) to solve tasks with minimal experience. Incorporating models of EM in RL can enable rapid learning and facilitate solving long-distance credit assignment problems. These models typically treat EM as a pure record-keeping system for sensorimotor data, but psychology and neuroscience understand EM to have broader capabilities. In the brain, EM maintains conjunctive representations of spatial, temporal, and sensorimotor elements of experience. Moreover, EM is not an ever-expanding repository of experienced information. Rather, many processes exist to promote both active and passive forgetting, and research suggests this is beneficial for learning. Additionally, experiential information is used by multiple memory systems. Animals may initially rely on memories of individual events to guide behaviour, but experience with repeated stimulus-outcome associations also informs habitual memory systems. Thus, with training, behaviour may come to rely more on learned associations rather than memory for any specific experience. In this work I present an episodic control system for RL navigation tasks which incorporates some of these features of biological EM. I compare this episodic control system against the learning profile of a traditional RL agent and show that episodic control can make use of minimal data to leverage successful behavioural policies in a few-shot manner. I show that episodic control using representations of events which contain relational information offer greater performance advantages than unstructured sensory data, especially under conditions where agents experience moderate forgetting. Finally, I explore how the behaviour of agents using episodic control may be used to provide off-policy training data for network-based model-free RL agents, and how this may ameliorate the data-inefficiency inherent to such systems.
Explorations on Beyond Endoscopy
Keywords: Beyond Endoscopy
Langlands
Orbital Integral
Orders
Zeta Functions

In this thesis we provide a description of the first paper on Beyond Endoscopy by Altug and explain how to generalize to totally real fields, based on a joint work of the author with Melissa Emory, Debanjana Kundu and Tian An Wong, and is a work in preparation. This part is mostly expository, and we refer the reader to the relevant paper. Furthermore, we prove a conjecture of Arthur. In his original paper on Beyond Endoscopy, Langlands provides a formula for certain product of orbital integrals in GL(2, Q), subsequently used by Altug to manipulate the regular elliptic part of the trace formula with the goal of isolating the contribution of the trivial representation. Arthur predicts this formula should coincide with a product of polynomials associated to zeta functions of orders constructed by Zhiwei Yun. We prove this is the case by finding the explicit polynomials and recovering the original formula from them. We also explain how some aspects of the strategy used can be interpreted as problems of independent interest and importance of their own. En esta tesis damos una descripción del primer articulo sobre Más Alla de la Endoscopía por Altug y explicamos como generalizarlo a campos totalmente reales, basados en un trabajo conjunto con Melissa Emory, Debanjana Kundu y Tian An Wong, y él cuál sigue en estado de preparación. Esta parte es mayormente una exposición y referimos al lector al artículo relevante. Además, demostramos una conjetura de Arthur. En su artículo original sobre Más Allá de la Endoscopía, Langlands da una fórmula para cierto productos de integrales de órbita en GL(2, Q), subsecuentemente utilizadas por Altug para manipular la parte regular eliptica de la formula de traza con el objectivo de aislar la contribución de la representación trivial. Arthur predice que esta formula coincide con un producto de polinomios asociados a funciones zeta de órdenes construidos por Zhiwei Yun. Demostramos que esto es cierto mediante hallar los polinomios explicitos y recuperamos la formula original a partir de ellos. Más aún, también explicamos como algunos aspectos de esta estrategia pueden ser interpretados como problemas de interés e importancia independiente.
Investigation of the Serological Changes that Discriminate Asymptomatic Antinuclear Antibody Positive Individuals from Systemic Autoimmune Rheumatic Disease Patients
Keywords: Microarray
Microparticles
Sialic acid
Systemic autoimmune rheumatic diseases
Systemic lupus erythematosus

The Antinuclear antibody (ANA) associated Systemic Autoimmune Rheumatic Diseases (SARDs) are chronic rheumatic disorders associated with high morbidity. Many patients with these diseases have irreversible tissue damage at disease presentation. Current therapies aim to control symptoms and prevent further damage by lessening the inflammatory immune response through broad and often aggressive immunosuppression, which leaves patients vulnerable to numerous side effects. Although ANAs are a serological hallmark for the ANA-associated SARD, they are also seen in healthy individuals, most of whom will not progress to disease. This not only precludes their use as biomarkers of progression but also indicates that their presence alone is insufficient to induce tissue damage and symptoms. Elucidating the serological differences between ANA-associated SARD patients and asymptomatic ANA+ individuals and the underlying immune mechanism(s) that led to these differences will permit identifying individuals at increased risk of progression and enable the development of better therapeutic targets. Here, we show that although the type, number, and levels of specific auto-antibodies (auto-Abs) remained stable over a 2-year follow-up period in the subset of asymptomatic ANA+ individuals that developed new SARD symptoms, these individuals have elevated levels of anti-Ro52 auto-Ab as compared to those that did not progress. We also demonstrated that SARD patients have very high levels of IgG auto-Abs as compared to ANA+ individuals that lack a SARD diagnosis, that are not detected by current screening techniques, arguing for the introduction of assays with a better dynamic range and discriminatory capacity. Additionally, we found that the IgG of SARD patients has a reduced sialic acid content, as compared to healthy controls and asymptomatic ANA+ individuals, which correlated with an increased ability to induce a pro-inflammatory response by monocyte-derived dendritic cells, serum levels of TNF- and the proportion of circulating T follicular helper 17 cells. These findings enhance our understanding of the underlying immunologic dysregulations that promote the transition from asymptomatic autoimmunity to disease and suggest that therapies that target these pathways may be useful to prevent progression to SARD.
Dissonance Reimagined: Tone Clusters in Leo Ornstein’s Early Piano Music
Keywords: avant-garde
dissonance
Leo Ornstein
piano
tone cluster

It can be argued that the contributions of Russian-American composer Leo Ornstein (1895-2002) to the American musical avant-garde movement have not yet been sufficiently acknowledged. His piano works from the 1910s prominently feature heavily-dissonant tone clusters, used in a great variety of musical contexts. Known most commonly for creating massive, aggressive sounds, they were integrated by Ornstein into music of a much more colouristic compositional idiom.The first chapter of this dissertation concerns the history of tone clusters on the modern piano and provides historical context for Ornstein’s own application of them. Little scholarship exists on the specifics of Ornstein’s usage of the technique. This dissertation documents the many uses of clusters and other extreme dissonances in his music from 1913-1918, arguably the most experimental period of his compositional career. Seven pieces are discussed in detail in the second chapter: Danse Sauvage, S054 (1913)Dwarf Suite, S052 (1913) Impressions of Notre Dame, S056 (1914) Impressions of the Thames, S053 (1914) The Cathedral, S073 (1915) Poems of 1917, S061a (1917) À La Chinoise, S060 (1918) The tone clusters contained within are analyzed for their harmonic content, registral and formal placement, and the manner in which they are played, among other considerations. More general assessments of these pieces, concerning other elements of dissonance not specifically falling into the category of clusters, are also offered. The third and final chapter begins with a discussion of how Ornstein integrates elements of more minor dissonance, and less frequent clusters, into music of a more traditional idiom. His clusters are then compared to those written by George Antheil and Henry Cowell, two other composers of the period most often associated with the technique, a comparison which reveals several differences in approach.
Identifying SLAP2-TRIM21 as a Novel Endogenous Recycling Complex of EGFR in Lung Cancer
Keywords: cell signaling
EGFR
genome editing
lung cancer
protein interactions
systems biology

The epidermal growth factor receptor (EGFR) is the most-studied member of the receptor tyrosine kinase (RTK) family of proteins, particularly as a driver oncogene in non-small cell lung cancer (NSCLC). Targeted therapeutic approaches to inhibiting EGFR activity with receptor tyrosine kinase inhibitors (RTKi) have proven limited, considering lung cancers can acquire resistance to these molecules by developing EGFR mutations or overexpressing other RTKs. To produce more robust molecular therapies, more critical drug targets must be elucidated within cancers. One approach to doing so is to discover novel mechanisms that regulate EGFR in lung cancer. I accomplished this by using novel technologies for detecting protein-protein interactions, the Mammalian Membrane Two Hybrid (MaMTH) and Split Intein Mediated Protein Ligation (SIMPL) assays, to detect novel Src-homology 2 (SH2) domain containing proteins which interact with EGFR in an activation dependent manner. This yielded SLAP2 as a novel interactor of EGFR, which I functionally characterized in H460 NSCLC cells. Using a sleeping beauty transposon system, I overexpressed FLAG-tagged wildtype and mutant isoforms of SLAP2, which demonstrated that SLAP2 upregulates EGFR and maintains expression after ligand stimulation. Then using affinity purification coupled to mass spectrometry, we identified TRIM21 as an interactor of SLAP2 that maintains EGFR expression post activation. Finally, I used CRISPR/Cas9 to deplete endogenous SLAP2 levels in H460 cells showing downregulation of EGFR expression post activation, and subsequent recovery of EGFR upregulation with transient overexpression of SLAP2, validating the endogenous function of this interaction in non-small cell lung cancer.
Novel Gene Therapy Platforms and a Mouse Model for Lysosomal Storage Disorders
Keywords: Enrichment
Gene therapy
Lentivirus
Lysosomal storage disorder
SMA-PME
T-Rapa

Cell and gene therapies are the epitome of personalized medicine for inherited disorders. Lysosomal storage disorders (LSDs) are particularly amenable to treatment by such therapies, as overexpression in some cells may suffice to treat the deficiency in uncorrected cells by “cross-correction”. The hematopoietic system is an accessible compartment of cells that can be readily and safely transduced with lentivirus (LV) ex vivo. Hematopoietic stem and progenitor cells (HSPCs) from patients with LSDs can be engineered with LV to overexpress the deficient enzyme and transplanted back into patients. This strategy is under clinical investigation for some LSDs, including Fabry disease. Results from such clinical trials highlight areas of improvement.We aimed to leverage the potential of lymphocytes as more specific target cells for gene therapy. T and B cells are abundant in peripheral blood. Unlike HSPCs, T cells can be expanded ex vivo without loss of function. We first tested LV-modified rapamycin-conditioned T cells (T-Rapa) as alternative long-lived hematopoietic cells for treatment of LSDs. We demonstrated enzyme secretion from LV-modified T-Rapa cells in vitro, and reduction of accumulated substrate in vivo. Next, we tested a strategy to enrich for transduced T and B cell progeny in response to mycophenolic acid (MPA) following HSPC-directed gene therapy. Resistance to MPA was engineered by co-expression of mutated inosine-5’-monophosphate dehydrogenase 2 (IMPDH2IY) with therapeutic transgenes using a dual-promoter vector. In vitro testing with cell lines and primary T cells revealed enrichment of IMPDH2IY-expressing cells was possible with extended low-dose MPA treatment. We also established two in vivo models to test enrichment using this platform. In addition, we aimed to establish a murine model of acid ceramidase deficiency with spinal muscular atrophy-like phenotypes. Adequate animal models are needed to test efficacy of novel therapeutic platforms, including those described in this thesis. We modified a previously established mouse model of Farber disease by excision of intronic elements. We characterized spinal cord pathology in this new derivative strain which includes wide-spread demyelination in the white matter and sphingolipid accumulation. Together, our work provides the framework for novel gene therapy platforms and describes tools for testing them.