VictorJuiz/thesis huggingface dataset:
Towards Functional Imaging Biomarkers of Alzheimer's Disease

There is a growing need for biomarkers of Alzheimer's Disease (AD) to aid in early detection, tracking of treatment response, and drug development. Functional magnetic resonance imaging (fMRI) has been a focus of efforts, offering a dynamic view of the affected organ. We first examined the existing fMRI literature in AD research using a quantitative meta-analysis of episodic memory studies comparing AD patients and healthy older adults. We found a consistent loss of medial temporal lobe (MTL) activation in patients, but both reduced and increased cortical activation outside of the MTL, including areas of increased activation likelihood in the ventral lateral prefrontal cortex (VL-PFC). These findings suggest some evidence for compensatory hyperactivation in individuals with AD. We next collected both task- and resting-state fMRI data in 16 individuals with mild AD and 13 healthy older adults, and examined the default mode network (DMN) dysfunction in order to determine whether DMN abnormalities vary depending on how they are measured (i.e., rest vs. task). Patients showed resting state deficits in the multiple regions but none during task completion. The change in DMN connectivity in the posterior cingulate between rest and task was predictive of cognitive status in patients, while measures at rest or task alone were not. This suggests that a measurement of change in DMN connectivity may provide unique clinical information unavailable to a single state scan. In chapter 4 we examined the sensitivity of a simple visual task and resting state DMN measures to pharmacological treatment with a cholinesterase inhibitor (ChEI) in AD. Twenty-three patients with AD and 13 healthy matched controls were scanned twice, an average of 7 months apart, with patients receiving ChEI treatment after scan 1. ChEI treatment was associated with increases in visual, parietal and VL-PFC activation in patients, which persisted after controlling for perfusion in individuals with perfusion MRI data. DMN connectivity was disrupted at baseline within the right MTL and showed increased left MTL coactivation with treatment. Controls showed no changes over time. These results suggest that long term ChEI treatment is associated with changes in task-relevant cortical activation and MTL-DMN connectivity, but these changes were not associated with measures of clinical status.

Keywords: Alzheimer's Disease
cholinesterase inhibitor
default mode network
functional MRI
functional neuroimaging
Advisor: Black, Sandra E
Complex Mechanics of Constrained Connective Tissue Matrices and their Impact on Cellular Mechanosensation

Physical interactions of cells with matrix microenvironments are critical steps in many cellular processes such as mechanosensation and metastatic invasion. Mechanosensory processes are strongly influenced by the composition and mechanical properties of the matrix, which in turn determines cell behavior. Several experimental strategies use homogeneous scaffolds to study cell behavior as a function of matrix microstructures. However, native matrix structures are highly heterogeneous in their organization and composition, which complicates understanding and definition of fundamental elements of mechanosensation. Accordingly, the sensory mechanisms used by cells to interpret matrix complexities, such as tissue boundaries, remain elusive. I developed a new model system to examine how lateral physical boundaries interfere with cell-induced compaction and remodeling of collagen and how these processes drive cell extension formation. The length and number of cell extensions were dependent on the distance of the cell from the physical boundaries. In the absence of physical boundaries, the resistance of thin collagen matrices to cell-generated forces was dependent on deformation rate. At rates similar to cell-induced deformations, native collagen matrices exhibited pronounced inelastic behavior, which in turn reduced tension in the network. Thus strain rate-dependent inelastic properties of collagen matrices may strongly influence cell-matrix interactions and matrix remodeling. Further, I determined that the actin cross-linking protein filamin A is required for cell-induced maintenance of tension and matrix compaction when resisted by physical boundaries. My findings underline the complex mechanics and structures of connective tissue matrices as determinants of cellular mechanosensation.

Keywords: Collagen
Filamin A
Integrin
Mechanobiology
Nonlinearity
Remodeling
Advisor: McCulloch, Christopher A
A Pedagogy for Conducting Vernacular Music of Spanish Latin America

Spanish Latin American musics emerged through multiple heritages and influences present among the countries, with variations based on local conditions. Although performances of Latin American choral music in North America have increased over the past years, generally these performances have a tendency to flatten the richness of the musics, ignoring the wide variety of practices across the continent. Additionally, there is a lack of written sources for choral conductors about Latin American vernacular genres, since those were generally transmitted through oral tradition. Therefore, the goal of this dissertation is to provide pedagogical suggestions based on reliable audio versions of various Latin American vernacular genres, to assist conductors and teachers in the creation of appropriate interpretations. This study is organized in three stages, thus providing a model for Latin American repertoire studies: Historical Context, Aural Analysis and Interpretative Analysis. These three stages acknowledge the musics' primary musical influences, compare vocal techniques and instrumentation of the studied audio versions, and connect those to a score through an interpretative analysis. Throughout this dissertation, readers will find pedagogical approaches to interpret Spanish Latin American vernacular genres, using tools that are accessible in North America. Various tables summarize the conclusions drawn from this study.

Keywords: Ana Alvarez
Folkloric
Latin American
Music
Pedagogy
Vernacular
Advisor: Apfelstadt, Hilary
Packman, Jeff
Regularized Partially Functional Quantile Regression

We present a quantile regression model where the response variable is scalar while the explanatory variables involves both infinite-dimensional predictor processes-viewed as functional data, and high-dimensional scalar covariates. Despite extensive work focusing on functional linear models, there is little effort devoted to the development of robust methodologies that tackle the scenarios of non-Gaussian processes. This motivates our proposal of functional quantile regression that seeks alternative solution to least squares type procedures, within the partially functional regression framework. We focus on inferring a sparse representation of the high-dimensional covariates but the problem is complicated by the nature of functional data. To this end, we simultaneously employ two types of regularization, involving truncation and shrinkage techniques, to select and estimate relevant scalar covariates while taking the functional components into consideration. Theoretically, we show that our proposed penalized quantile estimators enjoy oracle properties such as consistency and asymptotic normality, under some mild conditions. Monte Carlo simulations support our theoretical findings and an application to brain imaging data demonstrates the advantages of our method over alternative approaches.

Advisor: Yao, Fang
Polarization Control for Silicon Photonic Circuits

In recent years, the field of silicon photonics has received much interest from researchers and companies across the world. The idea is to use photons to transmit information on a computer chip in order to increase computational speed while decreasing the power required for computation. To allow for communication between the chip and other components, such as the computer memory, these silicon photonics circuits need to be interfaced with optical fiber. Unfortunately, in order to interface an optical fiber with an integrated photonics circuit two major challenges need to be overcome: a mode-size mismatch as well as a polarization mismatch. While the problem of mode-size has been well investigated, the polarization mismatch has yet to be addressed. In order to solve the polarization mismatch one needs to gain control over the polarization of the light in a waveguide. In this thesis, I will present the components required to solve the polarization mismatch. Using a novel wave guiding structure, the hybrid plasmonic waveguide, an ultra-compact polarization rotator is designed, fabricated, and tested. The hybrid plasmonic rotator has a performance similar to purely dielectric rotators while being more than an order of magnitude smaller. Additionally, a broadband hybrid plasmonic coupler is designed and measured. This coupler has a performance similar to dielectric couplers while having a footprint an order of magnitude smaller. Finally, a system solution to the polarization mismatch is provided. The system, a polarization adapter, matches the incoming changing polarization from the fiber actively to the correct one of the silicon photonics circuit. The polarization adapter is demonstrated experimentally to prove its operation. This proof is based on dielectric components, but the aforementioned hybrid plasmonic waveguide components would make the system more compact.

Advisor: Mojahedi, Mo
Is There In Choice No Beauty? Motivation for Choosing Moderates Choice Overload

Some research suggests that increasing the number of options may be harmful for consumers by increasing their difficulty with choosing, which increases their likelihood of experiencing regret. However, other research suggests that increasing the number of options may also be beneficial by satisfying consumers' diverse tastes and variety-seeking needs. Thus, it isn't clear whether - or when - more choice would be harmful or beneficial for consumers. I propose that the motivation for choosing as either extrinsic or intrinsic impacts consumers' satisfaction with the chosen option differently. For extrinsic choices where consumers are choosing an option to achieve some separable consequence, more choice increases the difficulty with choosing, which decreases satisfaction. For intrinsic choices where consumers are choosing an option for its inherent rewards, more choice increases the autonomy from choosing, which increases satisfaction. Crucially, this difficulty or autonomy occurs because consumers perceive variety with more choice, even though more choice does not necessarily mean a greater objective amount of variety. I conclude by discussing how understanding the motivation for choosing has implications for researchers and marketers who study or provide choice to consumers.

Keywords: autonomy
choice
choice overload
extrinsic motivation
intrinsic motivation
preference construction
Advisor: Mitchell, Andrew A
Alcohol Use and Risk Drinking in Ontario Ethnic Groups

This thesis examines the prevalence and patterns of alcohol consumption among Ontario ethnic groups, as well as socio-demographic and cultural factors that increase or reduce their vulnerability to risk drinking. A mixed methods approach was applied. Qualitative data were obtained through focus group discussions with the key informants and community members from seven Ontario communities: the Polish, Portuguese, Russian, Tamil, Punjabi, Serbian and Somali. Quantitative data were derived from the CAMH Monitor, a cross-sectional survey of Ontario adults, collected between January 2005 and December 2010 (N=13,557). The results show higher prevalence of self-reported lifetime, current and risk drinking among the Canadian and the European-origin groups compared with other ethnic groups. Within-group gender differences were evident for all ethnic groups, with the narrowest gender gap being observed within the North European group and the widest in the South Asian group. First generation immigrants have generally lower prevalence of alcohol consumption and risk drinking than Canadian-born respondents, with foreign born individuals from the European groups reporting higher rates of alcohol use and risk drinking than other groups. While previous studies generally found an increase in immigrants' alcohol consumption with years in Canada, our data suggest that longer duration of residence may have either positive or negative effects on immigrants' alcohol use, depending on the country of origin/traditional drinking pattern. Although the non-European ethnic groups have higher rates of abstinence and lower alcohol consumption rates, a considerable proportion of people from these ethnic groups may be at risk of alcohol-related harm due to risky and harmful alcohol consumption patterns. Drinking levels that are considered `normal' or 'excessive', the type and size of alcoholic beverages, and the perception of the risks and problems related to alcohol use are largely shaped by cultural norms and beliefs. Socio-economic disadvantages and barriers to service utilization heighten the minority ethnic groups' vulnerability to alcohol-related problems. This theses contributes new and important evidence on the prevalence and patterns of alcohol consumption in Canada's ethnic groups, and factors that contribute to risk drinking. The findings have significant implications for prevention and service provision, particularly for minority ethnic groups that are already marginalized and unlikely to access mainstream services.

Keywords: alcohol
etnicity
gender
imigrants
risk drinking
Advisor: Mann, Robert E
Upper Bounds for the Gromov Width of Coadjoint Orbits of Compact Lie Groups

This thesis is devoted to the problem of estimating the size of balls that can be symplectically embedded in symplectic manifolds. This symplectic invariant is known as the Gromov width of a symplectic manifold. More precisely, we show an upper bound for the Gromov width of coadjoint orbits of compact Lie groups with respect to the Kostant-Kirillov-Souriau form. This upper bound extends a Theorem of Zoghi for regular coadjoint orbits; and in type A it complements a result of Pabiniak on lower bounds for the Gromov width of coadjoint orbits. The upper bound for the Gromov of coadjoint orbits of compact Lie groups found in this thesis is estimated by computing a non-vanishing Gromov-Witten invariant with one of its constraints being a point. The approach presented in the thesis is closely related to the one used by Gromov in his celebrated non-squeezing theorem.

Keywords: Coadjoint Orbits
Gromov Width
Gromov Witten invariants
J-Holomorphic Curves
Schubert Varieties
Symplectic Capacities
Advisor: Caviedes Castro, Alexander
Structure, Change over Time, and Outcomes of Research Collaboration Networks: The Case of GRAND

In this dissertation, I study the interplay between the structure of a collaborative research network and the research outcomes produced by its members. To achieve this goal, I examine GRAND (an acronym for Graphics, Animation and New Media), a Canadian network with over 200 researchers funded by the Canadian government. I use the social network analysis (SNA) framework in order to aid in understanding the structure of the GRAND collaborative research network as well as how it changes over time. I look at the changes of the network's structural characteristics over time and how they interplay with the researchers' outcomes. Thereafter, I explain this interplay by discussing the changes of the structural network's characteristics as conditions that can potentially affect a researcher's social capital and that can, in turn, affect the researcher's outcomes. Using data collected through two online surveys, and research outcomes paper-based survey, I was able to capture the research networks (structure and changes over time) of GRAND researchers while also being able to obtain the perceptions of these individuals about their research outcomes. These networks captured four types of interaction among GRAND researchers: co-authorship of scholarly publications, communication activity, advice exchange, and interpersonal acquaintanceship. My sample consisted of 101 GRAND researchers, a subset of these researchers (N=50) were subsequently interviewed. My findings lend support to the argument that social capital and social networks, when combined, yield richer theory and better predictions than when used individually. The social networks analysis conducted in this research offer precise measures of the social structure and documents the changes in the GRAND research network. The social capital-driven findings help move beyond the relations themselves to understand how personal relationships or social structures can either facilitate or hinder the achievement of different research outcomes. These results offer to substantiate previous work, while drawing attention to the importance of analyzing interpersonal networks when studying factors effecting research outcomes. This direction for future study is especially relevant, as research collaboration continues to increase both in scope and in importance.

Keywords: Mixed methods
Research collaboration
Research outcomes
Social capital
Social network analysis
Advisor: Lyons, Kelly
The Derivation of the Myocardial, Epicardial and Endocardial Lineages from Human Pluripotent Stem Cells

The adult heart is composed of cells from three major lineages: the myocardium, the epicardium and the endocardium. The myocardium is the working muscle and comprises primarily the ventricles and atria. The epicardium represents the outer epithelial layer that surrounds the myocardium and plays a pivotal role during cardiovascular development. This cell layer supports rapid proliferation of embryonic ventricular cardiomyocytes, is the major source of coronary vascular smooth muscle cells and cardiac fibroblasts and may promote remodeling of the heart after cardiac infarct in the adult. The endocardium is the specialized inner endothelial lining of the heart chamber and contributes to the formation of valves. The endocardium also exerts paracrine effects on the adjacent myocardium, promoting the proliferation and maturation of cardiomyocytes during the formation of ventricular trabeculae. While protocols for the efficient generation of cardiomyocytes from human embryonic and induced pluripotent stem cells (collectively referred to as human pluripotent stem cells; hPSCs) have been developed, strategies for the generation of the epicardium and endocardium do not exist. In this thesis, I show that through stage-specific manipulation of the BMP, canonical WNT and BFGF pathways it is possible to successfully direct the differentiation of hPSC-derived mesoderm towards the epicardial and endocardial lineages. Access to these cell types will enable investigations on their role in human cardiovascular development, application for cardiac regenerative medicine and modeling of cardiovascular disease.

Keywords: cardiomyocytes
endocardium
epicardium
Pluripotent Stem Cells
Advisor: Keller, Gordon
Synthetics Strategies for the Rational Design and Evaluation of Nanomedicine

Despite decades of research into new drugs and contrast agents, cancer remains prevalent around the world. Advances in nanotechnology have shown that colloidal nanocarriers have the potential to improve the performance of anti-cancer agents through more localized delivery, provided that the physical properties of these carriers, such as their geometry and surface chemistry, can be tuned precisely in order to control their interactions with biological systems. Building on this knowledge, this thesis describes the development of synthetic techniques to manipulate the physicochemical properties of nanomaterials for evaluating and controlling their biological delivery. Specifically, the development of fluorescently-labeled gold nanoparticles for in vivo imaging, the use of polymers to encapsulate semiconductor nanocrystals, as well as the combined use of organic and inorganic nanotechnologies to design nanocarriers for cancer targeting, are discussed. Overall, these studies provide researchers with tools to design and evaluate engineered nanomaterials for cancer related medical applications, and provide a synthetic framework towards future design of more sophisticated nanomedical devices.

Keywords: Cancer
Drug delivery
Molecular assembly
Nanomedicine
Nanotechnology
Advisor: Chan, Warren C.W.
Shin, Jumi A
The Sandwich Synapse: Trans-glial Signaling Between Neuronal Somata in the Dorsal Root Ganglion

The dorsal root ganglion (DRG) contains the cell bodies of primary somatosensory neurons that form axonal connections for the transfer of sensory input from the peripheral nerve receptor to the spinal cord in the central nervous system. In general, DRG neuronal somata (NS) are each enveloped by individual satellite glial cell (SGC) sheaths. However, a subset of NS are closely-apposed and separated solely by a thin SGC membrane septum, forming a structural cell trimer. Using patch clamp electrophysiological recording, we reported that repetitive stimulation of one NS evokes a delayed, noisy and long-duration inward current in both itself and its passive partner. Several lines of evidence demonstrate that transmission between the two NS is via a bi-synaptic, trans-glial pathway that we term a `Sandwich Synapse'. The first, NS to glial cell, synapse involves ATP release from the neuron and purinergic activation of the glial cell. The second, glial cell to NS, synapse is glutamatergic. We find that inter-NS transmission at the DRG Sandwich Synapse involves Ca

Keywords: dorsal root ganglion
glutamatergic
patch clamp
purinergic
trans-glial
T-type channel
Advisor: Stanley, Elise F