VictorJuiz/thesis huggingface dataset:
Development of an Ultra-high Frequency, Piezoelectric, Aptamer Based Sensor Platform for Small Molecule Detection

Many current aptasensor signal transduction methodologies are designed around the binding mechanism of the aptameric probe. Furthermore, many sensor designs are dependent on a label or signal amplification techniques, adding assay complexity to achieve the sensitivity levels required. The matter is further complicated when small molecule targets are considered. The work presented in this PhD thesis outlines the development of an acoustic wave aptasensing platform that provides more universality in terms of compatible aptamer binding mechanisms. A cocaine aptamer was employed as the aptamer-ligand model system and two aptamer constructs were studied; the rigid MN4 construct that only undergoes tertiary folding upon ligand binding and the MN6 variant that undergoes secondary structure ordering and tertiary structure folding in the presence of cocaine. Aptameric probes were anchored to the surface through an organic adlayer. Several surface configurations were evaluated until an optimized configuration was attained. The first sensor constructed was based on the MN4 construct, whose solution affinity for cocaine that is 7 fold higher than MN6 and exhibited an apparent Kd of 45 ± 12 µM, and a limit of detection of 0.9 µM. The MN6 (structure-switching aptamer) based sensor achieved an apparent Kd of 27 ± 6 µM, and a limit of detection of 0.3 µM, comparable to cocaine aptasensors that implement a signal amplification step. Repeated regenerability of both sensors and the ability to operate in multi-component matrices with multiple interferences was also demonstrated. The work presented within this thesis reveals a sensor platform that functions with both rigid and structure-switching aptamers in the same format while maintaining a facile one step assay without the use of a label or additive and a simple two-step surface preparation. This work constitutes the first piezoelectric aptasensor featuring the probe immobilized to an organic adlayer coated surface to directly detect the binding of a small molecule.

Keywords: Aptamers
Biosensors
bulk acoustic wave sensor
cocaine detection
organic monolayer
piexoelectric sensor
Advisor: Thompson, Michael
The HLA Complex Group 9 Gene Modification Study in Major Psychosis

Epigenetic mechanisms can offer new insights into the non-Mendelian features of complex psychiatric disorders. The first epigenome-wide scan in major psychosis, conducted by our group, identified DNA modification differences at HLA complex group 9 (non-protein coding) gene (HCG9) in the post-mortem brain samples of individuals affected with schizophrenia (SCZ) and bipolar disorder (BPD). In this thesis we present results from bisulfite pyrosequencing based fine mapping of a ~700 bp region of HCG9 in 1,402 DNA samples from post-mortem brain, germline (sperm), and peripheral white blood cells (WBC) of SCZ and BPD patients as well as unaffected controls. We observed significant differences in CpG modification between BPD samples and controls across all tissues and demonstrated the utility of WBC DNA modification density as an epigenetic marker for BPD. We further extended our analysis to full length HCG9 with bisulfite padlock probe-based deep sequencing in SCZ, BPD and control post-mortem brain samples. We identified significant differences in CpH modification between sense and anti-sense DNA strands and between major psychosis patients and controls. Next, we characterized genome-wide distribution of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in neural and non-neural tissue from mice and humans. 5-hmC has been recently found to be abundant in brain but its function is poorly understood. We assayed 5-hmC by using glucosylation coupled with restriction enzyme digestion and microarray analysis. We detected enrichment of 5-hmC in genes with synapse-related functions and tissue-specific differential distribution of 5-mC and 5-hmC at the exon-intron boundary. This boundary change was mainly due to 5-hmC in the brain but due to 5-mC in non-neural tissue. Our study suggests a new role for 5-hmC in RNA splicing and synaptic function in the brain. Finally, we determined 5-mC and 5-hmC modification density at HCG9 CpG6 in post-mortem brain tissue and WBCs of SCZ, BPD and control samples. Consistent with our previous report, we identified significant differences between the major psychosis group and controls, which were due to 5-hmC but not 5-mC as it was previously assumed.

Keywords: bipolar disorder
bisulfite sequencing
DNA modification
epigenetics
micorarray
schizophrenia
Advisor: Petronis, Arturas
Feedback Regulation of Human Hematopoietic Stem Cell Fate

Hematopoietic stem cell (HSC) fate decisions at least in part determine cellular composition of the hematopoietic system. It is known that differentiated blood cells produce ligands that act on HSCs to influence HSC fate. However, fundamentals underlying the feedback regulation of HSC fate are poorly understood. Here, we explored the fundamentals of the feedback regulation of HSC fate at the microenvironmental, intercellular (between cells), and intracellular (inside a cell) levels. First, we developed a machine learning algorithm to decompose heterogeneous blood cell samples isolated from cell culture. The results suggest the microenvironmental condition in which HSCs reside affects their transcriptional program. Further, we explicitly mapped feedback signals from 11 differentiated blood cells to HSCs by integrating microarray data, bioinformatics databases, and high content in vitro screening data. The results demonstrate the existence of blood cell type-specific feedback effect on HSC fate decisions. Intriguingly, we found that HSC self-renewal inducing ligands and proliferation inducing ligands were enriched in the NF-κB pathway and the STAT3 pathway, respectively. We constructed a kinetic model of the NF-κB – STAT3 pathway. The model serves a foundation for future development and optimization, and the final model could generate hypotheses of extracellular and intracellular intervention for controlling in vitro HSC expansion. Overall, this work has laid a conceptual and technical foundation for investigating cell-cell communication in other multicellular dynamic systems; one important application is in the use of cell-cell communication as a therapeutic avenue to treat various diseases.

Keywords: computational biology
feedback regulation
hematopoietic stem cell
systems biology
Advisor: Zandstra, Peter W
Financial Health Incentives in Cardiac Rehabilitation

Financial health incentives, such as paying people to exercise, are being widely implemented despite limited evidence of their effectiveness. Accordingly, the objectives of this work were to (1) examine the efficacy of incentives-for-exercise in adults, (2) determine the potential for incentives to promote long-term exercise adherence (> 6 mo.) and (3) to explore incentive ‘acceptability’ and efficacy in cardiac rehabilitation (CR). A comprehensive CR outpatient program designed to help individuals recover from and manage their cardiovascular disease (CVD) was a suitable initial target for incentives in Canadian health care since many CVD risk factors are under behavioural control (e.g., physical inactivity). To determine the impact of incentives on exercise adherence in adults a systematic review and meta-analysis of randomized trials was conducted. In this review incentives increased exercise adherence 80% of the time, by about 12% on average (SD 5.61%, 17.50%; test for overall effect z=3.81, p

Keywords: Cardiac Rehabilitation
Exercise
Health behaviour change
Incentive
Reward
Advisor: Faulkner, Guy E
Goodman, Jack M
Advanced Silicon Photonic Device Architectures for Optical Communications: Proposals and Demonstrations

Photonic integrated circuits implemented on silicon (Si) hold the potential for densely integrated electro-optic and passive devices manufactured by the high-volume fabrication and sophisticated assembly processes used for complementary metal-oxide-semiconductor (CMOS) electronics. However, high index contrast Si photonics has a number of functional limitations. In this thesis, several devices are proposed, designed, and experimentally demonstrated to overcome challenges in the areas of resonant modulation, waveguide loss, fiber-to-chip coupling, and polarization control. The devices were fabricated using foundry services at IBM and A*STAR Institute of Microelectronics (IME). First, we describe coupling modulated microrings, in which the coupler between a microring and the bus waveguide is modulated. The device circumvents the modulation bandwidth vs. resonator linewidth trade-off of conventional intracavity modulated microrings. We demonstrate a Si coupling modulated microring with a small-signal modulation response free of the parasitic resonator linewidth limitations at frequencies up to about 6× the linewidth. Comparisons of eye diagrams show that coupling modulation achieved data rates > 2× the rate attainable with intracavity modulation. Second, we demonstrate a silicon nitride (Si

Advisor: Poon, Joyce
Conspicuous Peripheries: Black Identity, Memory, and Community in Chatham, ON, 1860-1980

The history of the black population in Chatham, Ontario is incomplete by virtue of partiality and distortion. This partiality and distortion has had real, if difficult to quantify costs for Chatham's local black population. While it is a worthwhile and necessary project to recuperate lost local histories for their own sake in order to encourage and inform the reframing of larger national and historically more influential histories, this study also focuses on the history of black people who lived in Chatham in the nineteenth and twentieth centuries in order to explore situated black lives that were actively constructed and performed. This deliberate attempt to expand the historiography of blacks in Canada from that of black-as-object to black-as-subject required an investigation into the local history of blacks in Chatham, their socio-philosophical and socio-economic heritages and the construction of particular identities shaped by race, class, and gendered interests forged within a shared experience of ongoing white racism. Informed by census data, primary fraternal order documents, and oral testimony, this study also holds that dislocations occurred at the turn of the twentieth century that concretized class membership, exacerbated class distinctions all while complicating the tenability of a coherent and cohesive black community.

Keywords: Black Canadians
Black history
Census
Chatham
Masons
Advisor: Morgan, Cecilia
Legacies: Kinship and Change in Kumasi, Ghana

This study situates current kinship and inheritance practices among the matrilineal Asante within an analysis of cultural and legal change. Based on 18 months of fieldwork in Kumasi, Ghana, I analyze matrilineal kinship and marriage by considering the ways in which ongoing kin relations influence inheritance decision-making in conjunction with broadly shared notions of custom or law. I critically examine a supposed schism between “traditional” and “modern” inheritance to show various points of convergence between past and present notions of inheritance and kinship. I show that people incorporate the principles of both state inheritance law and local custom in multiple ways, not just to distribute property during decision-making about inheritance, but to assign responsibility for the care of the sick or of children and to distribute the funeral debts. In contemporary Ghana, the period of inheritance decision-making is a time when profound ethical ambiguities in kinship and social relations become apparent. To understand how inheritance is changing, I argue that analysts need to discard assumptions that matrilineal kinship and marriage is inherently harmful to women as well as assumptions about the progressive nature of social change. Instead, I argue that inheritance is an emergent process that combines both general cultural knowledge and the particular knowledge of a deceased individual’s life and relationships to produce decisions that assign responsibility and reform relations that have been disrupted by death. From this perspective, both the significant social changes to and ongoing vitality of matrilineal kinship and marriage become apparent.

Keywords: Asante
Ghana
Inheritance
Kinship
Social change
Advisor: Bamford, Sandra
Multi-Winner Social Choice: Algorithmic and Game-theoretic Approaches

Decision-making problems in multi-agent settings are commonly characterized by the requirement to choose which items to assign to which agents, or choose which items to offer them for sale, given their preferences. We take an algorithmic approach to problems that commonly face agents in these domains, such as online retail websites (where the agents are vendors) or voting settings (where the agents are the voters). We study problems that are known to be computationally hard, and focus on approaches that deal with these tractability issues using techniques for approximating the optimal solutions. Our work has two recurring themes. First, we introduce competition among selfish agents (e.g., vendors or advertisers) as an additional factor in many of our problems. Second, we introduce an additional component of uncertainty (which comes in various forms), and which plays a key role in our models. This added uncertainty comes in two forms: online (sequential) arrival of the agents (e.g., as in physical stores), and distributional models, in which the decision-maker’s actions are based on probabilistic beliefs about the agents’ preferences. We develop algorithms for selecting the best sets of items in settings where such factors as uncertainty and competition introduce added complications. We also provide game theoretic analyses of settings where competition and uncertainty about the preferences induce best response dynamics in which the vendors iteratively update their strategies in response to each other.

Keywords: Algorithms
Game theory
Social Choice
Social Networks
Advisor: Borodin, Allan B
Boutilier, Craig E
Physiological, Pharmacological and Clinical Factors Associated with Thrombosis in Pediatric Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Postoperative thrombosis in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) is a frequent, under-diagnosed and clinically detrimental complication. The majority of known risk factors for thrombosis in this context are non-modifiable clinical correlates (notably younger age at surgery and cyanosis). We sought to identify modifiable physiological risk factors for post-operative thrombosis after pediatric cardiac surgery to inform the development of thromboprophylaxis strategies. Pediatric patients were prospectively enrolled before cardiac surgery with CPB in an observational cohort study. Children

Keywords: Epidemiology
Heart disease
Imaging
Pediatrics
Physiology
Thrombosis
Advisor: McCrindle, Brian W
Dynamical Signatures of Dark Matter Substructures on Tidal Streams

Despite the success of the LambdaCDM model at describing the universe on large scales, the model’s predictions are at odds with observations on sub-galactic scales. In particular, the model predicts that a Milky-Way-sized dark matter halo should contain substructures in the form of low mass subhalos. However, there has yet to be convincing evidence that these subhalos exist. One promising method to probe the abundance of subhalos is by their dynamical effects on tidal streams, which are elongated remnants of tidally disrupted stellar systems as they orbit around the host galaxy. Previous theoretical studies have shown that subhalos can induce longitudinal density variations (or “gaps”) along streams. Although gaps have indeed been observed in some streams, it remains unclear whether those gaps correspond to those expected from subhalos. Previous simulations used idealized models, which did not account for realistic effects that may also induce gaps along streams. In this thesis we investigate a number of these effects. In the first chapter, we simulate streams with self-gravity, in which we successfully model the gaps caused by epicyclic overdensities, intrinsic to the orbit of a stream, rather than subhalo perturbations. We show that the two kinds of gaps are distinguishable in their length distributions. In the second chapter, we simulate self-gravitating streams inside a realistic halo that is constructed from a high-resolution cosmological simulation. We find that streams with similar orbital apo- and pericenters can have very different morphologies which cannot be modelled in idealized halos. In the third chapter, we simulate a collection of self-gravitating streams inside the same realistic halo in order to quantify the difference between using an idealized halo and a realistic halo. We show that the shape of the halo has a large effect on the dispersal of streams. Nevertheless, we find that many of those streams still remain cold and thin. This suggests that upcoming stellar surveys are likely to discover more streams that are suitable for probing the abundance of subhalos.

Keywords: dark matter
dynamics
galaxies
streams
structures
subhalos
Advisor: Carlberg, Raymond G
The Development of Environmental Comprehensive Multiphase Nuclear Magnetic Resonance Spectroscopy

Soil is the most complex mixture on this planet and is central to the transport of contaminants, carbon cycling and sustainable agriculture. However, our understanding of soil is limited in large part due to the lack of analytical approaches that can provide detail information on molecular structure and interactions in the native state. Current pre-treatment practices remove key synergies between components that are responsible for soil's reactivity, kinetics, interactions and numerous other characteristics. Nuclear magnetic resonance (NMR) spectroscopy has played an integral role in furthering soil research because of its versatility and non-destructive nature, but has not been able to study all phases of matter (solid, liquids, and gels) at once in a whole unaltered soil. Recently, comprehensive multiphase NMR (CMP-NMR) was introduced and combines traditional NMR techniques resulting in an instrument that has capabilities allowing for whole soil analysis. After an introduction of soil and NMR, the rst two research chapters focus on solving two key issues with environmental NMR, sensitivity and water suppression through experimental means. Sensitivity is increased by focusing NMR signals into one single spike and forgoing chemical shift. The result is an experiment that can determine experimental run time in low concentration samples as well as a rapid detection system for use in kinetics or dynamics. In the next chapter, a robust water suppression method is developed and applied to real environmental samples including soil by building on the current standard, SPR-W5-WATERGATE. The latter two research chapters apply CMP-NMR to soil research by rst characterizing the composition and structure of soil in its native state. It is found that aliphatic and carbohydrate components are available at the water interface while proteins from microbes and lignin are buried under the surface with hydrogen bonds and hydrophobicity playing a key role in their protection. Finally, contaminant interactions are probed in all phases where kinetics, sorption orientation, and soil binding domains are characterized in all phases. As a whole, this thesis helps to develop CMP-NMR for use in soil research and positions it as an important novel NMR technology with potential widespread application in a range of elds including materials research, biology, biochemistry and medicine.

Keywords: Comprehensive Multiphase
Nuclear Magnetic Resonance
Organic matter
Soil
Advisor: Simpson, Andre J.
Sport and Physical Recreation in Canadian Federal Prisons: An Exploratory Study of Carceral Physical Culture

Despite their prominence in correctional environments around the world, sport and physical activity are understudied areas of prison life, including in Canada. Furthermore, even less attention has been paid to how prison sport and physical recreation intersect with the many other physical practices in prisons that, this dissertation argues, together compose a carceral physical culture. This thesis addresses this gap through an exploratory study of the historical development and social significance of carceral physical culture in Canadian federal prisons. The thesis includes a detailed historical examination of the development of the Canadian corrections system and its impact on physical culture, using a variety of primary and secondary sources to develop this analysis. It also draws on important theoretical perspectives from the sociology of everyday life—particularly the theoretical work of Erving Goffman, Michel de Certeau, and Henri Lefebvre—to explore the micro-level significance of physical culture in prisons. This analysis engages with the complex social meanings of sport and physical activity in an environment of extreme deprivation—what Goffman (1961a) calls a total institution—and the ways these practices are implicated in social control and resistance. Delving deeply into the broad range of physical cultural practices with which prisoners engage, and situating these within the micro- and macro-level structures that contour the social world of prisons, not only provides insight into the social significance of sport and physical activity in an unusual social context—it also allows for interpretive analysis about the operation of power in total institutions, the social production of space in and through physical culture, and the complex ways in which powerful actors exercise social control and marginalized groups resist these impositions.

Keywords: corrections
physical culture
prison
sociology of sport
sport
total institution
Advisor: Donnelly, Peter
Kidd, Bruce