VictorJuiz/thesis huggingface dataset:
Early Outgrowth Cells As A Novel Therapy for Chronic Kidney Disease

Chronic kidney disease (CKD) and its cardiac complications represent a large and growing problem in Canada. The progression of CKD is driven by the activation of several final common pathways of injury, including fibrosis and oxidative stress. If left unchecked, these inter-connected processes lead to progressive damage and subsequent organ dysfunction. Current clinical therapies, consisting of aggressive blood pressure control and blockade of the renin-angiotensin system, fail to arrest this progressive injury in a significant number of patients. Early outgrowth cells (EOCs) represent a novel bone marrow-derived cell population that have been recently described to have tissue protective activity. In this work, we examined the effects of intravascular EOC infusion in two independent models of CKD, demonstrating potent anti-fibrotic renoprotective effects in the subtotally nephrectomized (SNX) rat, a well-established model of non-diabetic progressive CKD, and anti-fibrotic and anti-oxidant effects in the db/db mouse, a commonly used model of type 2 diabetic nephropathy. In the SNX rat, which is characterized by impaired cardiac relaxation reminiscent of a common and high risk clinical CKD phenotype, EOC infusion was also associated with improved cardiac structure and function. In both cases, infused EOCs were not retained in significant numbers within the diseased kidney or heart, but rather localized to distant organs such as the liver, spleen, and bone marrow. We further demonstrated that EOCs release soluble factors with anti-oxidant and anti-fibrotic activity in vitro, and that a cell-free preparation of EOC-derived factors can mimic the reno- and cardiac protective effects of the cells themselves when infused into the SNX rat. Taken together, our results demonstrate the therapeutic potential of an EOC-based strategy for the treatment of CKD and its cardiac complications, and provide the preclinical rationale for the design of clinical trials of EOC-based therapies for this devastating disease.

Keywords: chronic kidney disease
heart failure
fibrosis
diabetes
oxidative stress
cell therapy
Advisor: Gilbert, Richard
Aspects of Linguistic Integration of Recent Immigrants to Canada: Determinants of English Language Proficiency, Role of English in Labour-market Integration Outcomes and Skills Utilization

The thesis explores the determinants of English proficiency as well as its role in labour-market integration outcomes and skills utilization. The Longitudinal Survey of Immigrants to Canada provides the data for the empirical analysis. The introductory chapter offers insight into the recent changes to the Canadian immigration policy as well as immigration trends. This chapter also outlines chapters Two through Six and establishes the conceptual framework that unifies them. Chapter Two introduces two theoretical approaches, human capital theory and macro-level factors of the source and destination countries’ framework. It presents a review of the literature and introduces a theoretical model of linguistic integration that is subsequently tested in Chapters Three and Four. Chapters Three and Four focus on the application of human capital theory and macro-level factors of the source and destination countries’ framework. Chapter Three explores the factors that contribute to the immigrant’s English proficiency upon arrival. Chapter Four investigates the role of human capital and destination country’s macro-level factors in English proficiency four years after migration. The principal empirical results indicate that macro-level factors of the source country are significantly related to the English proficiency at arrival, while macro-level factors of the destination country are significantly related to English proficiency four years after migration. The results also corroborate findings described in the human capital literature aiding comprehension of the relationship between human capital endowments and English proficiency. Chapter Five investigates the role of English proficiency in such labour-market integration outcomes as employment seeking, incidence of employment, and employment within ethnic enclaves. The study finds that English proficiency is associated with higher odds of employment seeking and employment in Canada. It also significantly increases the likelihood of being employed outside ethnic enclaves. Chapter Six integrates human capital theory and language as a dimension of ethnicity framework. The analysis concentrates on the role of English in immigrants’ skills utilization. The principal results add to human capital theory, indicating that English proficiency significantly increases the odds of skills utilization. The findings also reveal that immigrants who speak standard English are more likely to utilize their skills than non-standard English speakers.

Keywords: Immigration
Integration
Advisor: Hyatt, Doug
Early Fault Detection for Gear Shaft and Planetary Gear Based on Wavelet and Hidden Markov Modeling

Fault detection and diagnosis of gear transmission systems have attracted considerable attention in recent years, due to the need to decrease the downtime on production machinery and to reduce the extent of the secondary damage caused by failures. However, little research has been done to develop gear shaft and planetary gear crack detection methods based on vibration signal analysis. In this thesis, an approach to gear shaft and planetary gear fault detection based on the application of the wavelet transform to both the time synchronously averaged (TSA) signal and residual signal is presented. Wavelet approaches themselves are sometimes inefficient for picking up the fault signal characteristic under the presence of strong noise. In this thesis, the autocovariance of maximal energy wavelet coefficients is first proposed to evaluate the gear shaft and planetary gear fault advancement quantitatively. For a comparison, the advantages and disadvantages of some approaches such as using variance, kurtosis, the application of the Kolmogorov-Smirnov test (K-S test), root mean square (RMS) , and crest factor as fault indicators with continuous wavelet transform (CWT) and discrete wavelet transform (DWT) for residual signal, are discussed. It is demonstrated using real vibration data that the early faults in gear shafts and planetary gear can be detected and identified successfully using wavelet transforms combined with the approaches mentioned above. In the second part of the thesis, the planetary gear deterioration process from the new condition to failure is modeled as a continuous time homogeneous Markov process with three states: good, warning, and breakdown. The observation process is represented by two characteristics: variance and RMS based on the analysis of autocovariance of DWT applied to the TSA signal obtained from planetary gear vibration data. The hidden Markov model parameters are estimated by maximizing the pseudo likelihood function using the EM iterative algorithm. Then, a multivariate Bayesian control chart is applied for fault detection. It can be seen from the numerical results that the Bayesian chart performs better than the traditional Chi-square chart.

Keywords: Early Fault Detection
Hidden Markov Modeling
Advisor: Makis, Viliam
Stances on the Land: Political Perspectives on Land Use Governance in Vermont

Vermont, like many rural places in the developed world, has been the destination of many urban migrants seeking lifestyle amenities unavailable in the city. This migration has been blamed for intractable conflicts over land use governance, with newcomers pitted against long-time residents on such issues as wilderness designation, agricultural impacts and motorized recreation. How accurate, though, are these representations of political visions polarized along lines of residential status? This dissertation maps out the complexity of popular outlooks on land use governance in Vermont using a Q-method survey and semi-structured interviews. Analysis of the survey found evidence for two distinct perspectives on land use governance, which were termed Green Governance and Government Scepticism. While distinct, these perspectives were not diametrically opposed; on many issues of concern to one group the other group was neutral. These groups did not map directly onto residential status; in particular, long-time residents were clearly evident in both groups. Looking deeper into the stances on land use, tensions between stances are evident at both the level of the group and the individual. The dissertation traces these tensions and considers their implications for how individuals are enrolled in larger political projects such as neoliberalism. In many cases, uncertain enrolment suggests places where groups could productively engage each other and develop less antagonistic relationships. The dissertation fits the political orientations it examines into a broader cultural reading of social divisions that goes beyond residential status. It posits the existence of cultural complexes with an array of components contributing to social identity. These components – which include residential status and political orientation – influence each other without being determining. Compared with more established moral economy frameworks, this model seeks to provide a more flexible theorization of the relationship between social identity and political outlook.

Keywords: Land Use
Vermont
Politics
Social divisions
Advisor: Prudham, W. Scott
Oral Health for Long-term Care Populations: From Pneumonia Pathogenesis to Front-line Oral Care Provision

Oral health has dramatically improved in most industrialized countries over the latter half of the 20th century. However, profound oral health disparities still exist especially for those most at risk of developing oral diseases and associated systemic consequences such as populations residing in long-term care facilities. Despite the growing body of literature that supports the link between oral microflora and the importance of oral hygiene in limiting the risk of pneumonia development, there are still gaps in our knowledge to effectively manage this risk. The research included in this dissertation sought to further our understanding of oral health and oral care in the context of pneumonia pathogenesis (chapter 3) and, by exploring the perspective of various stakeholders in oral health, we sought to further understand the factors that influence care provision (chapter 5). Additionally, a novel knowledge translation approach was tested to challenge traditional oral care interventions in order to promote improvements in front-line oral care practices (chapter 6). The relationship between oral microflora, oral care and pneumonia was found to be complex. It directs us to consider converging risk factors including a patient’s health status, health behaviours and access to oral care services. Different professional groups were found to possess different definitions of oral health, which influenced both their motivation to provide care as well as their focus of care. Definitions of oral health could also potentially influence the saliency of different types of oral care information to different targeted groups; therefore, this should be considered in developing education and training initiatives aimed at improving the provision of oral care. An appreciative knowledge translation approach was found to be effective in bridging the gap between oral care knowledge and the provision of care. Regardless of the type of intervention chosen, organizations were reported to play a crucial role in promoting oral health and supporting the successful implementation of oral care programs.

Keywords: Oral health
Long-term care
Advisor: Steele, Catriona
Slow Flow of Viscoelastic Fluids Through Fibrous Porous Media

This thesis reports on an experimental study of slow viscoelastic flow through models of fibrous porous media. The models were square arrays of parallel cylinders, with solid volume fractions or ‘solidities’ of 2.5%, 5.0%, and 10%. An initial study using a Newtonian fluid provided a baseline for comparison with results for two Boger fluids, so that the effects of fluid elasticity could be determined. Boger fluids are elastic fluids that have near constant viscosities and can be used in experiments without having to account for shear-thinning effects. The experimental approach involved measurements of pressure loss through the three arrays and interior velocity measurements using particle image velocimetry (PIV). For the Newtonian flows, pressure loss measurements were in good agreement with the analytical predictions of Sangani and Acrivos (1982). PIV measurements showed velocity profiles which were symmetrical and independent of flow rate. Pressure loss measurements for the Boger fluid flows revealed that the onset of elastic effects occurred at a Deborah number of approximately 0.5, for both fluids and the three arrays. Flow resistance data collapsed for the two Boger fluids, and increased with solidity. For all three models, the flow resistance increased monotonically with Deborah number, reaching values up to four times the Newtonian resistance for the 10% model. PIV measurements showed that the transverse velocity profiles for the Newtonian and Boger fluids were the same at Deborah numbers below the elastic onset. Above onset, the profiles became skewed. The skewness, like the flow resistance, was observed to increase with both Deborah number and solidity. In the wake regions between cylinders in a column, periodic flow structures formed in the spanwise direction. The structures were staggered from column to column, consistent with the skewing. As either Deborah number or solidity increased, the flow structures became increasingly three-dimensional, and the stagger became more symmetric. An analysis of fluid stresses reveals that the elastic flow resistance is attributed to additional normal stresses caused by shearing, and not by extension.

Keywords: mechanical engineering
rheology
fluid mechanics
particle image velocimetry
piv
porous medium
cylinder array
periodic array
viscoelastic flow
creeping flow
slow flow
boger fluids
polymer solutions
fluid elasticity
periodic structures
cylinders
Advisor: James, David F.
Currie, Iain G.
Transition Metal Catalysis: Activation of CO2, C–H, and C–O Bonds En Route to Carboxylic Acids, Biaryls, and N-containing Heterocycles

Transition metal catalysis is a powerful tool for the construction of biologically active and pharmaceutically relevant architectures. With the challenge of continually depleting resources that this generation of scientists faces, it is becoming increasingly important to develop sustainable technologies for organic synthesis that utilize abundant and renewable feedstocks while minimizing byproduct formation and shortening the length of synthetic sequences by removing unnecessary protecting group manipulations and functionalizations. To this end, we have developed four new methods that transform inexpensive starting materials to valuable products. This dissertation covers the following key areas: 1) activation of CO2 for a mild and functional group tolerant synthesis of carboxylic acids, 2) oxidative twofold C–H bond activations as a strategy toward biaryls, 3) migratory O- to N-rearrangements in pyridines and related heterocycles for the preparation of N-alkylated heterocycles, and 4) asymmetric hydrogenations of cyclic imines and enamines en route to chiral 1,2- and 1,3-diamines and macrocyclic peptides.

Keywords: organic chemistry
synthesis
transition metal catalysis
carbon dioxide
organozinc reagents
carboxylic acids
nickel
C-H activation
biaryls
palladium
heterocycles
ruthenium
diamines
cyclic peptides
asymmetric hydrogenation
rhodium
Advisor: Dong, Vy Maria
Essays in Industrial Organization: Market Performance

This thesis consists of three papers. Industries that motivated this analysis range are exclusive clubs (Chapter 1) and pharmaceuticals (Chapters 2 and 3). A common thread is the study of the strategic behavior of monopoly or monopoly-like firms and the implications of such behavior. Chapter 1 studies an “invitation only” strategy for a durable goods monopolist. “Invitation only” functions as a commitment device, enabling the extraction of more profit than the conventional durable goods setting. In addition, the effectiveness of commitment devices in profit-extraction can be compared: each commitment device is modeled as an extra condition in the profit maximization of the general durable goods monopolist, enabling straightforward comparisons across commitment devices. Chapters 2 and 3 discuss the effect of patent protection on innovation in the pharmaceutical industry, in particular competition to produce drugs that follow-on from pioneer drug discovery, and any feedback effects on pioneer innovation. Despite the conventional notion, I show that longer patent protection may reduce or distort the incentives of innovation: with longer patents, the increased need of pioneer inventors in deterring the production of follow-on drugs may translate to less profitability for the pioneer inventor. Chapter 2 serves as a background and a literature review for Chapter 3. It explains the multi-stage drug discovery process and the phenomenon of follow-on drugs; it reviews strategic entry deterrence theories and summarizes the behavior of brand-name drug firms in deterring generic entry studied in the literature; it also reviews the optimal patent length and breadth literature. Chapter 3 presents several observed puzzles in the pharmaceutical industry and provides a unified explanation for these puzzles within a strategic entry deterrence model. The central conclusion is that under some general conditions, longer patent life distorts incentives for innovation and lowers research productivity: pioneer research is discouraged relative to follow-on research; inexpensive R&D projects are discouraged, and ceteris paribus expensive projects are favored instead, especially those with large clinical trial costs. Other predictions from the model accord with industry observations, including mid-development cancellations of potential drugs for non-medical reasons and early development of follow-on drugs in large markets.

Keywords: durable goods monopoly
pharmaceutical company
follow-on drugs
entry deterrence
Industrial Organization
strategic behavior
Advisor: Mathewson, Frank
{Spatial Tactile Feedback Support for Mobile Touch-screen Devices

Mobile touch-screen devices have the capability to accept flexible touch input, and can provide a larger screen than mobile devices with physical buttons. However, many of the user interfaces found in mobile touch-screen devices require visual feedback. This raises a number of user interface challenges. For instance, visually-demanding user interfaces make it difficult for the user to interact with mobile touch-screen devices without looking at the screen---a task the user sometimes wishes to do particularly in a mobile setting. In addition, user interfaces on mobile touch-screen devices are not generally accessible to visually impaired users. Basic tactile feedback (e.g., feedback produced by a single vibration source) can be used to enhance the user experience on mobile touch-screen devices. Unfortunately, this basic tactile feedback often lacks the expressiveness for generating vibration patterns that can be used to convey specific information about the application to the user. However, the availability of richer information accessible through the tactile channel would minimize the visual demand of an application. For example, if the user can perceive which button she is touching on the screen through tactile feedback, she would not need to view the screen, and can instead focus her visual attention towards the primary task (e.g., walking). In this dissertation, I address high visual demand issues found in existing user interfaces on mobile touch-screen devices by using spatial tactile feedback. Spatial tactile feedback means tactile feedback patterns generated in different points of the user's body (the user's fingers and palm in this work). I developed tactile feedback hardware employing multiple vibration motors on the backside of a mobile touch-screen device. These multiple vibration motors can produce various spatial vibration patterns on the user's fingers and palm. I then validated the effects of spatial tactile feedback through three different applications: eyes-free interaction, a map application for visually impaired users, and collaboration support. Findings gained through the series of application-oriented investigations indicate that spatial tactile feedback is a beneficial output modality in mobile touch-screen devices, and can mitigate some visual demand issues.

Keywords: Mobile device
Tactile feedback
Touch screen
User Interface
Advisor: Truong, Khai N.
Microfluidic Interfaces for Mass Spectrometry: Methods and Applications

Since the introduction of electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI), there has been an unprecedented growth of biomolecule analysis using mass spectrometry (MS). One of the most popular applications for mass spectrometry is the field of proteomics, which has emerged as the next scientific challenge in the post-genome era. One critical step in proteomic analysis is sample preparation, a major bottleneck that is attributed to many time consuming and labor-intensive steps involved. Microfluidics can play an important role in proteome sample preparation due to its ability to handle small volumes of sample and reagent, and its capability to integrate multiple processes on a single chip with the potential for high-throughput analysis. However, to utilize microfluidic systems for proteome analysis, an efficient interface between microfluidic chip and mass spectrometry is required. This thesis presents several methods for coupling of microfluidic chips with ESI-MS and MALDIMS. III Three microfluidic-ESI interfaces were developed. The first interface involves fabricating a polymer based microchannel at the rectangular corners of the glass substrates using a single photolithography step. The second interface was build upon the previous interface in which a digital microfluidic platform was integrated with the microchannel in a “top-down” format. The integrated microfluidic system was used for inline quantification of amino acids in dried blood spots that have been processed by digital microfluidics. The third interface was formed by sandwiching a pulled glass capillary emitter between two digital microfluidic substrates. This method is a simpler and more direct coupling of digital microfluidics with ESI-MS as compared to the method used for second interface. Finally, a strategy using a removable plastic “skin” was developed to interface digital microfluidics with MALDI-MS for offline sample analysis. We demonstrated the utility of this format by implementing on-chip protein digestion on immobilized enzyme depots.

Keywords: Digital Microfluidics
Mass Spectrometry
Microchannel
Electrospray ionization
Interfaces
matrix assisted laser desorption ionization
Advisor: Wheeler, Aaron