VictorJuiz/thesis huggingface dataset:
Improving diagnosis, understanding, and treatment of Farber disease

Farber disease (FD) is an ultra-rare Lysosomal Storage Disorder. It is caused by mutations in ASAH1, resulting in reduced activity of acid ceramidase and ceramide accumulation. The disease is poorly understood due to its rarity and the often short lifespan of patients. FD is systemic, with prominent hematological and sometimes neurological components. To better understand the disease, I characterized the hematopoietic and neurological effects of FD in the first mouse model, where the ASAH1 patient mutation P362R was knocked-in. Mice with FD have enlarged organs due to the accumulation of Mac-2+, foamy macrophages. This accumulation disrupts the organ architecture of hematopoietic-associated organs, including the BM and thymus, resulting in an almost complete loss of developing B and T cells in these organs, respectively, and an excess of hematopoietic stem and progenitor cells in the bone marrow. In the brain, mice with FD also have excess macrophages/microglia, astrocytosis, and hydrocephaly. To improve diagnosis of FD, I identified a plasma cytokine profile that distinguishes patients with FD from those with a disease that it is commonly misdiagnosed as, Juvenile Idiopathic Arthritis. The most elevated of these cytokines was monocyte chemotactic protein 1, and it alone or with the other elevated cytokines was associated with the presence of FD with 80% accuracy. These cytokines were normalized in FD patients who had received hematopoietic stem cell transplantation (HSCT). Finally, to reduce these signs of FD, I tested the efficacy of HSCT. HSCT from WT mice to FD mice more than doubled their lifespan from 7-13 weeks to a median of 27 weeks and a maximum of 40 weeks. Ceramide levels were normalized, and some peripheral signs of the disease were reduced. While beneficial, HSCT did not improve all symptoms. Through better diagnosis and understanding of FD, more effective treatments can be developed.

Keywords: Acid ceramidase
Ceramide
Farber disease
Farber lipogranulomatosis
Advisor: Medin, Jeffrey A
Retention of Primary Health Care Nurse Practitioners

The Nurse Practitioner (NP) role has emerged to meet the growing need for access to primary health care (PHC). To ensure that the NP role is sustainable and provides access to PHC for Ontarians, there is a need to examine NP work environments and NP responses to their work environments, such as retention. Currently, factors influencing the retention of primary health care NPs in Ontario are not well known. As Ontario continues to invest a large amount of health care spending in emerging PHC organizational structures to enable access to primary care, health human resource strategies for NP retention are essential. However, there is a paucity of literature on NP work, work environments, and their impact on important NP and health care system outcomes, including retention. The primary objective of this study was to investigate the underlying factors influencing retention of NPs in PHC in Ontario. The primary research question was: what are the effects of individual NP characteristics, NP practice characteristics, and NP organizational characteristics on PHC nurse practitioner intent to remain employed (ITR) in Ontario? A non-experimental descriptive cross-sectional survey design was implemented. Self-administered surveys were mailed to primary health care NPs in Ontario with follow-up using a modified Dillman approach. Two hundred and seventy-three surveys were completed resulting in a useable response rate of 52.9%. A hypothesized model of the underlying factors influencing ITR of NPs in PHC in Ontario was tested using multiple regression. Regression results indicate that administration-NP relations, work-life balance, and family situation significantly explained 14% of the variance in primary health care NP intent to remain employed in Ontario (p

Keywords: Intent to remain employed
Nurse Practitioners
Retention
Work Environments
Advisor: Tourangeau, Ann
Embodiment of Puebloan Childhoods: Towards a Bioarchaeology of Childhood

Thesis examines the construction of childhood identity among ancestral and historic Puebloans from American Southwest, based on the analysis of skeletal remains. Research is based on the premise that social identity becomes embedded in the physical body, and, therefore, in the skeletal remains of the individuals. Specifically, activities deemed appropriate for children of different ages, access to food, and exposure to risky behaviours and pathogens are expected to be reflected in growth, mortality and health patterns. With this in mind, I created a model for the study of childhood identity in skeletal population, that reflects the relationships between the environment, culture, individualâ s biological vulnerability and health. Model is then applied to the ethnographic Puebloan sources to construct the patterns of mortality, growth and non-specific stress indicators that are expected to reflect social construction of childhood identity among Pueblo tribes. Sample includes five archaeological sites (NAN Ranch, Grasshopper, Arroyo Hondo, Hawikku, and San Cristobal) that belong to the different periods of Puebloan history, are assigned to different archaeological cultures, and were inhibited by members of different ethnolinguistic groups. Analyses of mortality, growth and non-specific stress indicators confirms that the social construction of childhood does affect health, and as such can be identified through the analysis of skeletal remains. Comparison between modern, historic and ancestral Puebloans suggests that they shared similar construction of childhood, and common characteristics that diverge from the expected mortality and growth patterns. Specifically, following expected high mortality during first two years, mortality increases between 3 and 7 years of age compared to the expected mortality curve. This might be associated with the increased independence described in the ethnographic record. Growth analysis shows similar pattern, with juveniles exhibiting faltered growth until 5-6 years of age, followed by catch-up growth. This growth pattern is not observed only at the Grasshopper Pueblo, and this corresponds with the variability of childhood identity between Eastern and Western Pueblo tribes

Keywords: American Southwest
bioarchaeology
childhood identity
Pueblo tribes
skeletal analysis
social identity
Advisor: Schillaci, Michael A
Structure-function study of the IpaH family of bacterial E3 ubiquitin ligases

As a crucial mediator of the cellular response to infection, the ubiquitin system represents a major point of subversion by invasive pathogens. One mechanism of ubiquitin subversion shared among numerous Gram-negative bacteria is via the secretion of effector proteins belonging to the IpaH family. Once delivered into the host cell, IpaH effectors hijack the ubiquitin system by the action of a conserved C-terminal novel E3 ligase (NEL) domain, which catalyzes the covalent attachment of ubiquitin onto substrates bound at its N-terminal leucine-rich repeat (LRR) domain. When substrate is absent, IpaH enzymes are autoinhibited by inter-domain contacts between the LRR and NEL domains that prevent spurious catalytic activity and autoubiquitination. Although structures have revealed the unique fold of the NEL domain and conformations of the autoinhibited full-length enzyme, many questions remain as to how IpaH enzymes recognize substrates, how they catalyze ubiquitination, and how autoinhibition prevents catalytic activity. In this thesis, I use structural and biochemical methods to shed light on some of these questions. In chapter 1, I provide background on the ubiquitin system, the host-pathogen interface, the subversion of ubiquitin by bacterial effectors, and the IpaH family. In chapter 2, I present the first structure of an IpaH-substrate complex, resolved by X-ray crystallography. Using the structure as a guide, I probed the consequence of this interaction in cells. In chapter 3, I discuss my studies of the function of conserved residues in the NEL domain in which I identified two distinct surfaces that mediate either catalysis of ubiquitination or E2 binding. Also in this chapter, I explore the underlying mechanism of autoinhibition, revealing that the autoinhibited state permits charging and non-productive hydrolysis, but not aminolysis. In chapter 4, I present my efforts to stabilize IpaH catalytic intermediates for biochemical and structural studies. In addition, I show that the Shigella IpaH9.8 effector does not ubiquitinate its proposed substrate, NEMO, in vitro, indicating that substrate recognition is more complex than previously appreciated. Finally, in chapter 5, I explore future directions based on the work presented in this thesis.

Keywords: bacterial effector
E3 ligase
host-pathogen
IpaH
NEL domain
ubiquitin
Advisor: Sicheri, Frank
Paleoenvironmental and Paleotectonic Significance of Neoproterozoic Diamictites in Actively Rifting Basins

Thick successions of poorly-sorted admixtures of clasts and matrix (diamictite) are widely regarded as evidence for synchronous ‘panglacials’ of global extent during the Cryogenian period (c. 720-635 Ma). In this thesis, diamictite facies are examined in detail using an impressive collection of newly available sub-surface data consisting of some 300 km of drill core through the Grand Conglomérat, Democratic Republic of Congo, and by field investigations of the exceptionally well-exposed Kingston Peak Formation in eastern California, USA. Diamictites are shown to be of mass flow origin (debrites) present within thick (

Keywords: debris flow
diamictite
glaciation
rift basin
Sturtian
tectonics
Advisor: Eyles, Nick
Secondary School Principals and Leadership Coaching

The purpose of this qualitative study was to explore the experience of leadership coaching of secondary school principals. Twelve secondary principals who worked in Ontario along with five coaches who worked with secondary principals in Ontario schools were interviewed to solicit their ideas. The study was based on the main research question: How does leadership coaching as a professional development strategy support secondary principals? This was followed by three sub-questions: (1) How do secondary school principals describe their experience with leadership coaching? (2) How do coaches describe their experience with leadership coaching? (3) In the coaching process, to what extent do secondary principals and coaches believe that a change has occurred with secondary principalâ s leadership practices and beliefs? Most participants reported having a positive experience with coaching although some were hesitant with working with a coach initially. It was found that newer principals felt that coaching was more beneficially to support their work than more seasoned principals did as newer principals felt that the support of the coach helped with the steep learning curve. Some of the seasoned principals felt they were well-versed and confident in their work already. As well, a positive coaching relationship and a positive coachee disposition were key factors to ensure coaching success. It was found that coaching supported principals navigating through the challenges especially with resistive staff. It also helped with alleviating the loneliness of the job as it carried with it a social element for the principal. Changes to principal practices and beliefs were noted by most participants with a few participants indicated that no change resulted from the use of a coach. The study concludes with the notion that coaching is a good form of professional support for novice or seasoned principals should there be interest and quality coaching.

Advisor: Bascia, Nina
Deep Learning Models for Unsupervised and Transfer Learning

This thesis is a compilation of five research contributions whose goal is to do unsupervised and transfer learning by designing models that learn distributed representations using deep neural networks. First, we describe a Deep Boltzmann Machine model applied to image-text and audio-video multi-modal data. We show that the learned generative probabilistic model can jointly model both modalities and also produce good conditional distributions on each modality given the other. We use this model to infer fused high-level representations and evaluate them using retrieval and classification tasks. Second, we propose a Boltzmann Machine based topic model for modeling bag-of-words documents. This model augments the Replicated Softmax Model with a second hidden layer of latent words without sacrificing RBM-like inference and training. We describe how this can be viewed as a beneficial modification of the otherwise rigid, complementary prior that is implicit in RBM-like models. Third, we describe an RNN-based encoder-decoder model that learns to represent video sequences. This model is inspired by sequence-to-sequence learning for machine translation. We train an RNN encoder to come up with a representation of the input sequence that can be used to both decode the input back, and predict the future sequence. This representation is evaluated using action recognition benchmarks. Fourth, we develop a theory of directional units and use them to construct Boltzmann Machines and Autoencoders. A directional unit is a structured, vector-valued hidden unit which represents a continuous space of features. The magnitude and direction of a directional unit represent the strength and pose of a feature within this space, respectively. Networks of these units can potentially do better coincidence detection and learn general equivariance classes. Temporal coherence based learning can be used with these units to factor out the dynamic properties of a feature, part, or object from static properties such as identity. Last, we describe a contribution to transfer learning. We show how a deep convolutional net trained to classify among a given set of categories can transfer its knowledge to new categories even when very few labelled examples are available for the new categories.

Keywords: Boltzmann Machines
Deep Learning
Machine Learning
Neural Networks
Unsupervised Learning
Advisor: Hinton, Geoffrey E
Salakhutdinov, Ruslan R
The Examined Life: Relations Among Life Experience, Self-Reflection, and Wisdom

Little is known about how wisdom develops in everyday life. Laypersons and experts commonly assume that wisdom results from â life experience,â yet the nature and number of life experiences needed for wisdom development remains unknown. Many people amass diverse life experiences over time, but relatively few of them go on to become wise. There is much to learn about the psychological processes that support growth in wisdom through life experience. Relations among life experience, self-reflection, and wisdom were examined in a sample of 502 midlife adults ranging from 40 to 65 years of age. Participants completed an online survey that included closed-ended questionnaires and open-ended written tasks. A multi-method approach was taken to the measurement of wisdom, incorporating a range of self-report questionnaires and performance tasks. Results showed that wisdom was positively associated with the total number of events reported on a life-event checklist. At the level of event type, wisdom had positive linear relations with emotionally positive and culturally normative life events, and curvilinear relations with life events that were emotionally negative, culturally non-normative, and fundamental to life (inverted U-shaped curves). When asked to report autobiographical memories of wisdom-fostering life events, participants frequently recalled relationship events (e.g., interpersonal conflict, divorce), life-threatening or mortality-salient events (e.g., death, serious illness), and career or job-related events (e.g., job loss, skill development). On average, wisdom-fostering events were emotionally negative, culturally non-normative, and fundamental to life. Wisdom was positively associated with both self-report measures and narrative indicators (i.e., narrative coherence, autobiographical reasoning) of high-quality self-reflection. Moreover, self-reflection and life experience interactively predicted of wisdom. The highest levels of wisdom were associated with analytical forms of self-reflection among individuals who experienced either low numbers of positive events or high numbers of negative events. Finally, autobiographical memories of wisdom-fostering events had higher levels of narrative coherence and autobiographical reasoning when the event recalled was emotionally negative and culturally non-normative. Together, these results suggest that despite a robust relationship between wisdom and life experience, the strength and nature of this association depends on life-event characteristics and qualities of self-reflective processing.

Keywords: autobiographical memory
growth
life experience
narrative
self-reflection
wisdom
Advisor: Ferrari, Michel
Adaptive Functional Data Analysis

Statistical methods that adapt to individual observations or unknown population structures are attractive due to both numerical and theoretical advantages over their non-adaptive counterparts. In this thesis, we contribute to adaptive modeling of functional data, focusing on the fundamental aspects of representation and regression, where challenges arise from the infinite-dimensionality of their underlying spaces. For adaptive representation, the notion of mixture inner product spaces (MIPS) is developed, featuring an infinite-dimensional mixture of finite-dimensional subspaces. We show that MIPS provides a new perspective for representing functional data, in which each realization of the underlying process falls into a realization-specific component subspace whose dimension is larger for less smooth while smaller for smoother realizations. Moreover, MIPS also offers an alternative solution to the longstanding issue of nonexistent probability density for functional data. For adaptive functional regression, we are interested in the scenario that functional predictor process lies in a potentially nonlinear manifold that is intrinsically finite-dimensional but embedded in an infinite-dimensional function space. We propose a nonparametric estimator built upon local linear manifold smoothing that achieves a polynomial convergence rate and adapts to the intrinsic data geometry even when functional data are observed intermittently and contaminated by noise, in contrast to the logarithm rate in nonparametric functional regression literature. We demonstrate that both proposals enjoy favorable finite sample performance relative to commonly used methods via simulated and real data examples.

Keywords: Contaminated functional data
Functional data analysis
Infinite mixture
local linear manifold smoothing
Phase transition
Trajectory representation
Advisor: Yao, Fang
Identification, Estimation and Inference in Empirical Games

This thesis collects three papers studying topics related to the econometrics of empirical games. In Chapter 1, I investigate the identification and the estimation of empirical games of incomplete information with common-knowledge unobservable heterogeneity and potentially multiple equilibria realized in the data. I introduce pre-determined outcome variables to recover such unobserved heterogeneity. The recovered unobservables provide an extra source of exogenous variation that helps to identify the primitives of the model. I apply this method to study mobile telecommunications in Canada. I estimate a game in which national incumbents and new entrants choose the number of transceivers they install in different markets. The results highlight sizeable economies of density in transceivers location decisions. Counterfactual experiments shed light on the governmentâ s attempt to increase competition in this industry. In Chapter 2, I propose a test of an assumption commonly maintained when estimating discrete games of incomplete information, i.e. the assumption of equilibrium uniqueness in the data generating process. The test I propose is robust to player-specific common-knowledge unobservables. The main identifying assumption is the existence of an observable variable interpreted as a proxy for these unobservables. It must (i) have sufficient variation; (ii) be correlated with the common-knowledge unobservables; and (iii) provide only redundant information regarding the playersâ decisions and the equilibrium selection, were these unobservables actually observed. In Chapter 3, I study bias reduction when estimating dynamic discrete games. An iterative approach (the K-step estimator) is known to reduce finite sample bias, provided that some equilibrium stability conditions are satisfied. Modified versions of the K-step estimator have been proposed to deal with this stability issue. Alternatively, there exist other bias reduction techniques which do not rely on equilibriumâ s stability, but have not received much attention in this class of models. Using a dynamic game of market entry and exit, I compare the finite sample properties of the K-step approach with alternative methods. The results show that, even when the K-step estimator does not converge to a single point after a large number of iterations, it still considerably reduces finite sample bias for small values of K.

Advisor: Aguirregabiria, Victor
Encounters with Sociotechnical Encapsulation: Exploring Diagnostic and Pedagogical Interventions for the study of Literacy Practices in DIY and Maker Initiatives

Over the last few decades, scholars in various disciplines have raised concerns about notions of acquisition and delivery of technical skills. Rather than identifying specific skills or competencies, literacy practices entail heterogeneous phenomena in which the role of social, political, cultural, and technical dimensions needs to be carefully examined. What types of knowledge, skills, or expertise should count as literacy? How do we teach these skills and knowledge? How do we foster critical thinking and in-depth understanding of the relationships between society and technology? The proliferation of Do-It-Yourself (DIY) and Maker initiatives is increasingly becoming a major focus for scholars identifying these practices as emerging forms of literacy. This dissertation entails a conceptual and an empirical examination of Do-It-Yourself and Maker initiatives as a setting in which to situate and explore questions about emerging forms of literacy; in particular, how the use of DIY electronics can create innovative forms of collecting, interpreting, sharing, and negotiating the meaning of information. This research focuses on understanding how these practices allow people to engage creatively and critically in the construction of new forms of evidence, collaboration, and re-negotiations of meaning in their everyday life. The research method consists of iterative interventions engaging participants in the process of design and fabrication with DIY electronics. Throughout the case studies, I focused on the observation, documentation and assessment of the cognitive trajectories and inquiry practices afforded by the introduction of variations in levels of sociotechnical encapsulation and the progressive disclosure of the internal complexity of the electronic toolkits. Key findings of the dissertation include understanding how the engagement with material fabrication of DIY electronics can act as cognitive scaffolds leading to a progressive definition of communities of learners and the transformation of learning practices. The studies provide evidence of the value of engaging school teachers in exploring DIY and Maker initiatives not only as a pedagogical resource but also as a catalyst for reflection of their own professional practice.

Keywords: Arduino
Do-It-Yourself (DIY)
Learning Trajectories
Maker initiatives
Pedagogy
Sociotechnical Encapsulation
Advisor: Ratto, Matt