VictorJuiz/thesis huggingface dataset:
Movement Imagery-dependent Neuroplasticity can be predicted by Motor System Activation and Behavioural Assessments

Movement imagery (MI) is a cognitive motor process wherein a person consciously imagines themselves performing a movement. It has been demonstrated that MI can be an effective technique to generate and enhance motor learning and rehabilitation. These results may occur because the neural networks and processes involved in MI overlap with those of movement execution. The purpose of research reported in this thesis was to investigate the neural mechanisms involved in MI training and to link these mechanisms to behavioural measures of MI ability. Previous transcranial magnetic stimulation (TMS) studies have demonstrated that physical and observational training can temporarily modulate the excitability of cortical representations of movement in a manner consistent with the neuroplastic adaptations that occur through learning. This dissertation describes three experiments where TMS was used to assess similar training-induced modulations in the cortical representation of thumb movements following MI training. To investigate the neural mechanisms involved in these adaptations, the relationship between the magnitude of motor system adaptations and both neurophysiological measures during imagery and behavioural assessments of imagery ability were assessed. Three main conclusions were supported by the described research: 1) MI training can result in short-term adaptations in the motor system; 2) the magnitude of corticospinal excitability during imagery predicts the magnitude of motor system adaptations; and 3) behavioural measures of imagery ability associated with inter-individual differences in neural activation patterns during imagery can also predict the magnitude of motor system adaptations. Overall, this research has demonstrated that imagining movement alters the excitability of the motor system and can be an important mechanism for the initial process of motor learning using MI training.

Keywords: Imagery
Motor Imagery
Motor Learning
Movement Imagery
Neuroplasticity
TMS
Advisor: Welsh, Timothy N
Toronto's Housing Crisis: An Intersectional Politics of Housing and Settlement Services for Refugees

In this dissertation, I unpack the intersectional politics of the housing crisis in Toronto through the perspectives of frontline staff working in non-profit organisations. Two critical questions frame this study. Firstly, how have service providers addressed the housing and settlement needs of refugees in the context of Canada’s housing crisis? Secondly, how are race, class, language and citizenship status tied into the politics of housing and settlement service provision in Toronto? Utilising semi-structured interviews with frontline staff employed in various non-profit across Toronto, this research identifies and analyses systemic barriers to housing access among newly arrived refugees in Canada as they cut across race, class, language and citizenship status. This study interrogates the disjuncture between immigration and housing policies, programs and procedures and access to rental housing among refugees in Toronto. I draw on antiracist feminist frameworks, particularly intersectionality and theories of home-making, to enrich current conceptualisations of housing access and inequality in Canada. I unpack barriers refugees face when accessing the private rental market in Toronto, to reveal the multilayered ways in which marginalized communities experience housing inequality in Canada. In doing so, this dissertation reveals the limitations of the reliance on private housing stock for housing refugees as they face barriers, including lack of Canadian references and credit scores, lack of employment, language barriers and housing discrimination. Additionally, this study underscores the limitations of settlement and housing service provision available to vulnerable populations, such as refugees in Toronto. By engaging with the voices of frontline staff who consistently interact with refugees, this study sheds light on the intersectional praxis of service provision and the limitations service providers confront when administering programs for vulnerable populations in Toronto. Finally, this study unveils the roles community and grassroots organisations, such as the Ontario Coalition Against Poverty, Association of Community Organizations for Reform Now, and Parkdale Organize!, play in (re)imagining housing justice in Toronto. This study identifies and contributes a novel methodological and conceptual approach to housing research in geography by bringing to the fore frontline staff as a key category of analysis seldom featured in studies on Canada’s housing system.

Keywords: Housing access
Intersectionality
Refugees
Toronto
Advisor: Silvey, Rachel
Interactome Mapping of the Mitochondrial Intermembrane Space Proteases Identifies a Novel Function of HTRA2

Mitochondrial proteases are enzymes responsible for the breakdown of proteins within the mitochondria. A number of these unique proteases localize to specific sub-compartments of the mitochondria, but the functions of these enzymes are poorly defined. To better characterize these proteases, I used proximity-dependent biotinylation (BioID) to map the interactomes of seven proteases localized to the mitochondrial intermembrane space (IMS). In total, I identified 802 high confidence proximity interactions with 342 unique proteins. While all seven proteases co-localized with the IMS markers OPA1 and CLPB, 230 of the interacting partners were unique to just one or two protease bait proteins, highlighting the ability of BioID to differentiate unique interactomes within the confined space of the IMS. Notably, high temperature requirement peptidase 2 (HTRA2) interacted with eight of 13 components of the mitochondrial intermembrane space bridging (MIB) complex, a multiprotein assembly essential for the maintenance of mitochondrial cristae structure. Knockdown of HTRA2 disrupted cristae in HEK 293 and OCI-AML2 cells and led to increased intracellular levels of the MIB subunit IMMT. Using a cell-free assay, we demonstrated that HTRA2 could degrade recombinant IMMT, while two additional core MIB complex subunits, SAMM50 and CHCHD3 remained undegraded. Based on these findings, I further investigated the role of HTRA2 in acute myeloid leukemia (AML). Knockdown of HTRA2 in OCI-AML2 cells showed a decrease in cell growth and an increase in cell differentiation. Additionally, mice injected with HTRA2 knockdown AML cells displayed reduced engraftment, highlighting the role for HTRA2 in tumour cell growth in vivo. Lastly, I collaborated in the development of additional mitochondrial BioID datasets to help characterize the potential functions of these mitochondrial proteins. Overall, my characterization of the IMS protease interactome provides important biological context to an understudied class of proteins and represents a rich dataset that can be further mined to uncover novel IMS protease biology.

Keywords: Acute Myeloid Leukemia
BioID
HTRA2
Mitochondrial Biology
Mitochondrial Protease
Protein-protein interaction
Advisor: Schimmer, Aaron D
Raught, Brian
Identification and Inference for Functionals of Partially Identified Parameters

This thesis presents three essays related to identification and inference for functionals of partially identified parameters. This work is motivated by the fact that often the final object of interest in an empirical setting is not the whole vector of structural parameters, but is instead a single element of the parameter vector or, more generally, a functional of the parameter vector. A common theme throughout is that bounds on functionals of partially identified parameters can often be formulated as the solution to two stochastic optimization problems, one for the upper bound and one for the lower bound. In the first essay, we introduce an identification and estimation result for bounding functionals of the joint distribution of potential outcomes from the literature on treatment effects, and present an application to the evaluation of class sizes on test scores. The second essay considers the problem of inference for functionals of partially identified parameters defined in terms of stochastic linear programs. Under some regularity conditions, it is shown that a naive bootstrap procedure can be used to construct uniformly valid confidence sets for the true value of the partially identified functional of interest. In the final essay, the problem of counterfactuals and policy choice is considered. It is shown that a specific class of counterfactual objects, called policy transforms, can be bounded as the solution to two optimization problems without the need to impose parametric distributional assumptions on the latent variables in the model. The notion of learnability of optimal policies is defined, and sufficient conditions are provided for a class of policies to be learnable. Finally, finite sample theoretical guarantees for certain policy rules are derived. All chapters in this thesis are self-contained.

Advisor: Mourifie, Ismael
Wan, Yuanyuan
Redefining and Reclassifying Acute Traumatic Cervical Incomplete Spinal Cord Injury with Special Reference to Central Cord Syndrome: Implications for an Aging Population

In the face of the global aging population and the shifting epidemiology of acute spinal cord injury (SCI), there is a critical need to revisit the definition and clinical management of central cord syndrome (CCS). This dissertation investigated the hypothesis that the neurological outcomes of patients with ‘central cord syndrome’ are heterogeneous and predicted more accurately by acute clinical variables and interventions, including early surgical decompression. First, a systematic review of the literature pertaining to CCS was performed to identify: 1) predictors of outcome; and 2) the efficacy of early (

Keywords: Biostatistics
Central cord syndrome
Cervical spine
Clinical epidemiology
Spinal cord injury
Surgery
Advisor: Fehlings, Michael G
Ideological Freelancers The Politics of Legal Profession on Defense of and Offense against Authoritarianism

This dissertation studies the politics of the legal profession in political regime change from and to authoritarianism. To theorize the dynamics between the legal profession and power in democratization and political retrocession, I ask two questions: What is the role of the legal professions in the advancement and retreat of authoritarianism? What is the driving factor, the mechanisms and the consequences of the legal professions’ political mobilization? This project uses Taiwan and Hong Kong at the turn of the 21st century as two cases of study. These two jurisdictions invariably experienced fundamental power reconfigurations at the turn of the century, yet their politics drastically diverged in that Taiwan democratized but Hong Kong illiberalized. In both cases, legal professions - lawyers, judges and prosecutors - have stepped into the spotlight in various political arenas, on streets and in legislatures. I argue: the legal profession is a they, not an it. They are driven by normative commitments but serve instrumental roles to resist, dismantle, or facilitate authoritarian power in political transition. Specifically, the politically active legal practitioners exhibit two principal roles, on defense and offense, which encompass categorically different goals, strategies, rhetoric and intra-professional dynamics. Shaped by an exogenous political shock, they embody heterogeneous but not necessarily liberal commitments. The divergent political developments in Hong Kong and Taiwan lead to the defensive and assertive mobilization of the bar and bench. When authoritarian rule retreated, as in Taiwan, legal professionals were given the space to take assertive political actions to structure constitutional debates and crusade in a decade-long policy-making to substantiate a variety of normative commitments. Conversely in Hong Kong, when authoritarian rule advanced, the liberal lawyers mobilized to play the defensive roles, safeguarding judicial autonomy in parliament and in professional organizations. Moving onto a transnational perspective, this dissertation also notes how lawyers respond to the expansion of Chinese market. While economic integration moves across borders, jurisdictional boundary still matters as lawyers are agentic actors shaping policies that change or sustain the markets and hence the social structure of the bar.

Keywords: authoritarianism
democratization
Hong Kong
judicial politics
legal profession
Taiwan
Advisor: Hirschl, Ran
Wong, Joseph
Surrogate Model Assisted Nested Simulation with Applications to Variable Annuity Portfolio Valuation and Hedging

Variable annuities (VAs) are equity-linked annuities with embedded investment guarantees. Their long-term security and tax deferred features have made them one of the major insurance products in the world. Nowadays, many insurance companies are managing large VA portfolios that contain hundreds of thousands policies. Since most of the VA contributions are invested in the equity market, the insurance companies are exposed to significant market risks and risk managing the VA liabilities has become the central task. In practice, the stochastic-on-stochastic nested simulation is commonly used for VA portfolio valuation and risk management. The path-dependency of the embedded guarantees and the non-homogeneity of the VA policies make the nested simulation algorithm extremely complex and time-consuming to run. As a result, timely managing the portfolio risks becomes a major challenge to the insurance companies. The complexity of the nested simulation algorithm depends directly on three components: the number of policies, the number of outer-loop simulation, and the number of inner-loop simulation. In this thesis, we incorporate the idea of surrogate modelling to the nested simulation algorithm such that all of the input dimensions are reduced. The surrogate models act as proxies to approximate the input/output relationships. Since only a few input points are needed in order to identify the surrogate models, the simulation time could be shortened significantly. The key feature of the proposed algorithm is that the methodologies for selecting the inputs are theoretically justifiable from the statistical properties of the surrogate models. As a result, a robust performance can be ensured for the proposed algorithm in different context. Specifically, we introduce a model-assisted estimation framework with balanced sampling to reduce the number of policies, and a spline regression framework with scenario clustering to reduce the number of outer-/inner-loops. The proposed algorithm is applied to perform various valuations for large synthetic VA portfolios such as calculating the predictive liability distribution, the portfolio Greeks, and the regulatory capital requirement with dynamic hedging. The efficiency and the robustness of the algorithm are demonstrated through numerical studies on a number of uniform/non-uniform large synthetic VA portfolios and economics models.

Keywords: Balanced Sampling
Dynamic Hedging
Nested Simulation
Spline Regression
Surrogate Modelling
Variable Annuity Portfolio
Advisor: Lin, Xiaodong (Sheldon)
The Fanconi Anaemia Group M (FANCM) Protein and its Binding Partner FAAP24 Modulate ALT Telomere Maintenance in Human Cells

Telomeres are repetitive DNA sequences located at the ends of linear eukaryotic chromosomes. Malignant cells maintain their telomere length and their immortality by two mechanisms. The less studied mechanism is Alternative Lengthening of Telomeres (ALT), an opportunistic homologous recombination-based pathway that takes advantage of replication stress and uses Break Induced Replication (BIR) to maintain telomere lengths. Many DNA replication, repair, and recombination proteins are implicated in ALT, including several proteins defective in the chromosome instability syndrome Fanconi anemia (FA). We investigated the possible involvement of two FA pathway proteins in ALT: FANCM and its binding partner FAAP24. FANCM and FAAP24 form a heterocomplex, bind DNA, and facilitate recovery of stalled replication forks. We find depletion of either protein in human ALT cell lines leads to a hyper-ALT state, an exaggeration of the ALT phenotype marked by elongation of telomere ends as well as increases in extrachromosomal telomeric DNA (ECTR) content and fragile telomeres. The increase in ECTR content is due to increased ECTR numbers not their length. Increases in fragile telomeres suggested the loss of either FANCM or FAAP24 enhances replication problems despite increased telomeric DNA synthesis. We further explore the effects of FANCM and FAAP24 on ALT through co-depletion experiments with BLM and polymerase δ, two proteins involved in BIR. We found that the excess elongation of telomeres and increased ECTR DNA synthesis seen in FANCM- or FAAP24 ALT-depleted cells is dependent on BLM and pol δ. Using our novel Halo-FISH protocol, we found that depletion of BLM or pol δ could suppress the excess number of ECTR DNAs and chromosomal telomere length that are seen in FANCM and FAAP24 co-depleted ALT cells. We conclude that FA pathway proteins restrain ALT and suppress the hyper-ALT phenotype by limiting BLM/polδ-dependent BIR-driven telomere synthesis. We propose that FANCM and FAAP24 act to rescue stalled replication forks and disrupts D-loop formation during BIR initiation so as to to limit BLM/polδ-dependent BIR-driven telomere synthesis. Our findings support recent BIR-based models for ALT telomere synthesis while adding additional details as to the crucial role of replication fork collapse in ALT.

Keywords: Alternative legethining of telomeres
FAAP24
FANCM
Fanconi anaemis
Telomere maintenance
Telomeres
Advisor: Meyn, Stephen
Circles and Rivets: Cosmology and Teleology in Plato's Theory of the Soul

I propose a novel account of the soul in Plato’s philosophy as an entity that has surface, depth, location, extension, and is capable of contact and resistance. I take as my starting point Plato’s claim that the soul is the source of motion in the world and argue that while the soul has many characteristics normally associated with bodies, it is not a body. The distinguishing mark of the corporeal is visibility, and the soul is not visible. I show that we can see the spatial understanding of the soul most clearly in the Timaeus’ account of the soul’s creation. The soul is composed of eight circles. They are fashioned from incorporeal and corporeal varieties of Being, Sameness, and Difference. That the soul is half-corporeal and half-incorporeal allows it to interact with bodies in the way it needs to, but also relate to intelligible, incorporeal entities as a knower of them, which allows the soul to be the source of specifically orderly motion. Next, I take up an important consequence of the soul being in contact with bodies: it is vulnerable to them. Our soul is always in danger from bodily forces, and the body is the cause of all psychic disorders. I defend a new translation of a crucial sentence at Timaeus 86b that has been widely misunderstood. Nevertheless, the body is useful for the soul. The gods showed their resourcefulness when they made our bodies: they used the body’s inevitable imperfections to serve the goal of improving our souls. This is at the heart of what I call the instrumental relationship between the soul and body. I conclude by examining Plato’s theory of reincarnation. The theory functions as a natural-philosophical explanation of how non-human animals came into existence, which was required for the perfection of the cosmos. I argue that there is a trend, exemplified in the Timaeus and Laws, away from seeing reincarnation as a punishment for the individual soul and more towards thinking of it as useful for the perfection of the cosmos.

Keywords: Ancient philosophy
Body
Plato
Soul
Teleology
Timaeus
Advisor: Barney, Rachel
Controlled Organization of Cell Fates in Spatially Confined Stem Cell Populations

During embryonic development, cells divide and differentiate over space and time as instructed by their environment to create complex, functionally diverse tissues. Our understanding of the underlying orchestrating rules is incomplete, but recent studies have started to reveal how to instruct cultured pluripotent cell populations to undergo similar developmental-like organizational events. Here, we induce spatially polarized cell fate organization in micropatterned colonies, previously only reported for non-adherent or locally induced cell populations. Underlying this discovery was the augmentation of our micropatterning high-throughput platform through the development of analytical frameworks to automate the quantification of heterogeneous cell responses. These developments enabled rapid hypotheses generation and testing, which enabled new insights into the underlying biology of how and when cell fate organization occurs. Specifically, we developed analytical frameworks to accurately identify colonies of cells within an image and localization of positively expressing regions within these, which enabled automatic quantification of spatial fate organization. We show that when mouse pluripotent stem cells are differentiated on micropatterns towards gastrulation-like fates, their normally symmetrical spatial organization of cell fates can be modified by changing the micropattern diameter and cell density. By differentiating cells at low to medium density on circular micropatterns of 200-300 um in diameter, we induce polarized organization of primitive streak-like and anterior epiblast-like cells, reminiscent of how these populations are localized during development. We study the emergence of this organization using live imaging and found that polarization occurs largely due to reorganization within the colony post-induction. Overall, our results show that system size, both in terms of colony geometry and cell number at the time of differentiation, is critical for polarized cell fate organization. We hypothesize that this could indicate a need for developmentally relevant system sizes in polarization of micropatterned colonies, and that it might be driven by initial heterogeneities in colony morphology or cell fate distribution, or minor fluctuation that are allowed to amplify and perturb a homogeneous state. These insights on how to control and quantify fate organization in cell populations can advance both our understanding of developmental processes and how to create complex tissues with regenerative engineering.

Keywords: gastrulation
high throughput
image analysis
micropattern
stem cells
symmetry breaking
Advisor: Zandstra, Peter W