VictorJuiz/thesis huggingface dataset:
Reducing the impact of imported infections in Ontario
Keywords: burden
communicable disease
immigrant
surveillance
travel
visiting friends and relatives

Public health must remain responsive to the population’s changing health needs. As Canada’s diversity grows through immigration, protecting the health of immigrants when they travel to visit friends and relatives (VFR) is one such need. Immigrants comprise a growing proportion of international travelers and experience disproportionate travel-related infectious disease morbidity and mortality. While many infections are preventable, few immigrant travelers access pre-travel health services, in part because they are not covered under provincial health insurance plans. In my dissertation, I present three studies designed to respond to current gaps in evidence regarding how immigrant travelers perceive and respond to travel health risks, and how to measure travel-related disease burden. In the first study, I use qualitative methods to explore how South Asian travelers in Peel region conceptualize travel health risks. I found that travelers face many health challenges when traveling but adjust their behaviours to avoid or minimize key risks where possible. Their responses to risks, however, can be constrained by competing concerns (e.g. rushed travel, wanting to avoid family conflicts, cost, and a desire to enjoy traditional cuisine). These results highlight the importance of the social context in which travelers make health decisions. In the second study, I use novel data linkages to evaluate the utility of health administrative data for identifying hepatitis A, malaria and enteric fever infections. While diagnostic codes were sensitive, and additionally identified individuals who were likely unreported to public health, I found that their predictive value for accurately identifying cases was low. These results caution against the use of health administrative data, on its own, for this purpose. In the third study, I use a matched cohort design to estimate the health care utilization and attributable cost of hepatitis A, malaria and enteric fever infections in Peel region. Over three years, 318 cases resulted in more than $2 million dollars in direct health care spending, and attributable medical costs ranged from $4,500 - $8,000 per case. These results highlight that travel-related infections require substantial resources for diagnosis and treatment as most medically-attended cases require inpatient health care. Together, results from this dissertation advance our understanding of the complex social settings in which immigrant travelers make health-related decisions, and identify how much these avoidable infections cost Ontario’s health care system. Findings point to concrete opportunities to reduce disease burden through tailored health promotion strategies that are sensitive to the unique challenges immigrant travelers face. Costing estimates provide necessary model parameters to explore the cost-effectiveness of policies designed to improve access to pre-travel health services for high risk travelers.
Advanced Parabolic Equation-Based Propagation Modeling for Train Communication Systems
Keywords: Channel Modeling
Computational Electromagnetics
Finite-Difference Method
Parabolic Equation Method
Train Communication System
Wireless Communication

With the continuing expansion of metropolitan areas, the demand for efficient mass transportation systems is increasing accordingly. An emerging wireless technology for rail signaling, which can significantly improve the efficiency of light rail, subway, and high-speed train transit systems, is communication-based train control (CBTC). In CBTC systems, trains communicate wirelessly with wayside access points, which are connected to a central control station. A prerequisite for the deployment of such systems is the existence of a suitable propagation model, which can provide accurate path-loss predictions of corresponding wireless channels. This is of particular importance due to the safety-critical nature of rail signaling and the rapid, cost-effective nature of system deployment. This thesis presents an advanced propagation modeling tool, based on parabolic equation methods, to characterize radio wave propagation in realistic, complex railway environments. Concrete guidelines are provided on how to extract input models from point cloud data and what level of detail is necessary and sufficient to obtain results agreeing with measured data. Moreover, enhanced techniques dealing with geometrical variations of guideways and practical antenna patterns are presented. The accuracy and efficiency of the developed propagation model are demonstrated in various practical scenarios. Furthermore, a robust approach on extracting surrogate models from arbitrary tunnel geometries is proposed. The extracted surrogate models can lead to significant computational savings, especially in optimization studies where repetitive calls of the propagation model are required. The thesis also presents two hybrid propagation modeling techniques, aimed at achieving a better trade-off between accuracy, efficiency, and generality, via using the advantages of one method to compensate for the limitations of another and vice versa. Moreover, effects of uncertainty in the environment and experimental setup on the variability of predicted signal strength are investigated. A new approach that can incorporate wall roughness into the model is introduced. It can be applied to tunnels with arbitrary cross-section geometries and large-scale surface roughness. Finally, a physics-based optimization strategy is presented to optimize the placement of access points for train communication systems. The validity and usefulness of the proposed methodology are demonstrated in an actual deployment site of CBTC systems.
Modeling targeted therapy mechanisms and predictive biomarker discovery using human primary non-small cell lung cancer xenografts
Keywords: Drug tolerance
EGFR
Lung cancer
Patient-derived xenografts
Resistance
Targeted therapy

Lung cancer, the leading cause of cancer-related deaths worldwide, has recently been recognized as a large collection of molecularly-defined diseases. Molecularly-targeted therapies are revolutionizing clinical care for some molecularly-defined lung cancers. Perhaps the best studied example is targeting activating mutations of the epidermal growth factor receptor (EGFR) gene. Tyrosine kinase inhibitors (TKIs) have significantly improved clinically outcomes in lung cancer patients with these activating EGFR mutations. However, EGFR TKIs are not a cure as the vast majority of patients develop resistance. Some mechanisms of resistance to EGFR TKIs have been discovered, such as the secondary mutation in EGFR known as T790M which occurs in approximately half of patients. Third-generation EGFR TKIs can effectively treat T790M-positive disease; nonetheless, resistance develops against these inhibitors as well. Optimal treatments for the remaining 50% of non-T790M mediated resistance have yet to be determined, complicated by the fact that some mechanisms of resistance have not yet been discovered. To help identify further sources of resistance against EGFR TKIs, I leveraged our patient-derived xenograft (PDX) models of NSCLC with EGFR activating mutations. First, I demonstrated that these PDXs recapitulate patients’ tumour morphology, molecular biomarkers, and responses to targeted therapies. Next, the mechanism underlying an unexpected response to the single-agent EGFR-targeting monoclonal antibody Cetuximab was determined in one of our models with de novo T790M mutation. A third study identified a novel mechanism of resistance against an EGFR TKI and a corresponding effective treatment. Lastly, the origin of acquired resistance was explored, identifying and characterizing a sub-population of cells very similar to cells that can tolerate EGFR TKI treatment and act as a reservoir from which resistance develops. The knowledge gained from these studies provides novel and potentially clinically actionable biomarkers of response to EGFR TKIs in EGFR-mutant NSCLC.
Molecular and Device Engineering of Group 13, 14, 15 Phthalocyanines and Tetrabenzotriazacorroles for Organic Photovoltaic Applications
Keywords: Electronics
Materials Chemistry
Photovoltaics
Phthalocyanines

Phthalocyanines (Pcs) are a family of compounds that constitute a key building block of the organic photovoltaic (OPV) literature. Aside from their desirable optical and electronic properties, we are interested in Pcs because of their proven scalability and stability, unlike most organic semiconductors in literature. Although the Pc chromophores can chelate to almost all elements of the periodic table and conform to varying molecular structures, research in the context of OPVs has been largely concentrated on planar derivatives that chelate to metal centres without axial substituents. This render them molecularly unmodifiable hindering the understanding of structure-property-performance relationships of Pcs in the context of OPVs. In this dissertation, axially-bonding Pc compounds incorporating elements from groups 13, 14, and 15 into their cavities were engineered chemically by axial phenoxylation and by ring-contraction chemistry into tetrabenzotriazacorroles (Tbcs). The functionality of the modified molecules was also assessed in OPVs. Aluminum, silicon, and phosphorus were selected to represent tri-, tetra-, and penta- valent elements respectively. Series of axially-phenoxylated aluminum phthalocyanines (AlPcs) and silicon phthalocyanines (SiPcs) were synthesized, characterized, and incorporated into OPV devices. These easily prepared derivatives exhibited superior OPV performances in comparison to their baselines as electron acceptors. Tbcs which differ structurally from Pcs with the omission of a single imine nitrogen were unknown in the context of OPVs. This small difference in structure has paramount effects on the optical and electrochemical properties of the chromophore. For example, Tbcs exhibit a unique and desirable dual absorption of blue and red portions of the solar spectrum simultaneously. The first application of any Tbc compound in OPVs, oxy phosphorus tetrabenzotriazacorrole (POTbc) as a prototype, paired with conventional organic semiconductors is reported here. POTbc showed promise as an electron donating material due to its highly charged chromophore. POTbc was then coupled with boron subphthalocyanines (BsubPcs) as complementary absorbing donor-acceptor pairs in fullerene-free “black” OPVs. The outdoor stability of POTbc/BsubPc devices were assessed exhibiting on-par stability with their baseline. Further molecular structures of Tbcs, and resulting properties, were enabled through the synthesis of multiple Tbc derivatives chelating to a silicon center (SiTbcs).
Novel Phases in Hetero-Epitaxial and Super-Oxygenated Thin Films of Complex Oxides
Keywords: Heterostructure
High Tc Superconductor
Iridate
Structural Phase Transition
Thin Film
Yttrium barium copper oxide

In this thesis we study structural phase transition and defect structures in complex oxide thin films induced by either heterostructuring or superoxygenation, in an effort to understand their effects on the electronic and superconducting properties. Thin films were chosen for the ability to tune the heteroepitaxial strain, as well as their large surface-to-volume ratio. We focus on two families of oxides, including the cuprate superconductors Y-Ba-Cu-O (YBCO), and the Ruddlesden-Popper iridates Sr(n+1)Ir(n)O3(n+1). We examine the effect of heteroepitaxial strain on the superconducting critical temperature (Tc) of YBa2Cu3O(7-x) (YBCO-123) thin film. Strain-induced intergrowth of CuO defect structures is seen in La(2/3)Ca(1/3)MnO3 (LCMO)/YBCO-123 bilayer films, and can account for the reduced Tc in such bilayers. Perovskite/YBCO-123/perovskite trilayers with either ferromagnetic LCMO or paramagnetic LaNiO3 (LNO) as clamping layers show similarly strong reduction of the Tc. The Tc reduction is much milder when orthorhombic PrBa2Cu3O(7-x) (PBCO) is used as clamping layers instead. These results indicate that heteroepitaxial strain, rather than long-range proximity effect, is responsible for the long length scales of Tc reduction in LCMO/YBCO-123 heterostructures. We carried out superoxygenation experiments on YBCO-123 films in order to search for novel YBCO phases. YBCO-123 films are annealed in high-pressure oxygen, in conjunction with Cu enrichment by solid-state diffusion. The annealed films show clear evidence of phase transformation to Y2Ba4Cu7O(15-x) and Y2Ba4Cu8O16, increasing with higher degree of Cu enrichment. Regions of exotic phases containing multiple CuO or Y layers are also seen in high-pressure annealed films. Our results demonstrate a novel route of synthesis towards discovering more complex YBCO phases. We also carried out superoxygenation on Sr2IrO4 (SIO) films in an attempt to metallize the iridates via hole-doping. High-pressure oxygen annealed SIO films show a progressive drop in room-temperature resistivity of up to 3 orders of magnitude, and an evolution towards metallic behavior. The post-annealed films show transformation to SrIr(1-x)O3, increasing with annealing time, pressure, and reduced film thickness. The evolution towards metallicity is attributed to phase transformation, interstitial oxygens, and Ir vacancies. The Ir vacancies in the most phase-transformed film appears to be structurally-ordered along the c-axis. Our results demonstrate a novel method for hole-doping and phase-transforming the iridates.
Characterization of Two Opposing Small RNA Pathways Required for Germline Homeostasis in Caenorhabditis elegans
Keywords: Argonaute
c elegans
CRISPR
microRNAs
RNAi
small RNAs

Central to all small RNA pathways are the Argonaute (AGO) proteins, which interact with small RNAs to regulate gene expression in a sequence-specific manner. The characterization of AGOs across species has demonstrated that AGOs generally interact with different complements of small RNAs to perform distinct regulatory functions. In this thesis, I combined molecular biology and high-throughput sequencing to further characterize two small RNA pathways in Caenorhabditis elegans. First, I utilized the closely-related nematode species Caenorhabditis briggsae as a comparative genomics tool and determined that the CSR-1 pathway is functional in other nematode species. Next, I characterized two additional components of the CSR-1 pathway, CHP-1 and EMB-4, and implicated them in the loading of CSR-1 small RNAs and export of CSR-1 targets from the nucleus to the cytoplasm, respectively. Finally, I set out to characterize, C04F12.1, an AGO that is most closely related to CSR-1. Remarkably, I found that this AGO interacts with multiple classes of small RNAs, including the essential mir-51 family of microRNAs, which is known as the mir-100 in mammals, as well as subsets of piRNAs and CSR-1 22G-RNAs. mRNA and protein expression analyses demonstrated that C04F12.1 is broadly expressed throughout C. elegans development. Immunolocalization studies showed C04F12.1 expression predominantly in somatic tissues with dynamic nuclear localization in embryos. Genome-wide mRNA-seq data implicated C04F12.1 in silencing the expression of a large portion of germline-expressed genes. Furthermore, at elevated temperatures, C04F12.1 mutant embryos possess increased number of cells that aberrantly express germline markers. Thus, we propose a model in which C04F12.1 and its bound 22G-RNAs functions antagonistically to the CSR-1 pathway in somatic cells to silence germline gene expression and maintain somatic cell identity. Collectively, these studies have shed light on how different small RNA pathways can co-regulate mRNA targets to maintain the proper balance of gene expression.
A CSR-1 guided H3K36me3 Signature Maintains Germline Gene Expression Programs In Caenorhabditis elegans
Keywords: C elegans
development
epigenetics
gene regulation
small RNA pathways

Small RNA pathways related to RNA Interference (RNAi) are prevalent in species ranging from protozoa to mammals, including humans. These pathways contribute to organismal development and cellular function and elicit their gene-regulatory impacts through diverse modes of action. The soil nematode, Caenorhabditis elegans, has emerged as a powerful system to study the endogenous activities of these pathways. In the germline, the worm has evolved an intricate network of small RNA pathways, that jointly contribute to the transmission of epigenetic information through cell divisions and across generations. This activity is necessary for the maintenance of existing germline gene expression programs, and involves the dynamic regulation of mRNA transcripts, small RNA populations, and changes to the chromatin landscape. In this thesis, I demonstrate a role for the Argonaute CSR-1 (Chromosome Segregation and RNAi defecient-1) in this process. Using genetic approaches, I demonstrate that CSR-1 licenses genes for germline expression and overcomes the silencing activity of competing small RNA pathways. I explore the mechanisms by which CSR-1 elicits its licensing activity, and identify a role for the pathway in guiding the acquisition of H3K36me3 on a genome-wide scale. Using a combination of genetic and genome-wide approaches I describe the contribution of two H3K36 methyltransferases to the CSR-1 pathway. Finally, I identify a putative self-reinforcing loop involving H3K36me3 and small RNAs that together act to reinforce an epigenetic memory of past patterns of germline gene expression. Together, these studies contribute to the understanding of how various aspects of epigenetic regulation converge to faithfully maintain existing gene expression programs in eukaryotes.
Effects of Early Embryonic Ethanol Exposure on Adult Zebrafish Social Behavior
Keywords: embryonic alcohol
fetal alcohol
social behavior
zebrafish

The purpose of this thesis was two-fold: 1) to investigate preferences for various aspects of social stimuli in adult zebrafish, and 2) to investigate whether low-dose embryonic alcohol exposure affected how zebrafish responded to these various social stimuli. Control fish were exposed to different behavioral paradigms to measure responses to and preferences for various social and predator stimuli. Both male and female fish were found to prefer all-male shoals to all-female and mixed shoals, and zebrafish were able to reliably discriminate between larger shoals when ratios of 2 vs. 1 were employed. Fish avoided a moving predator image, and an elongated image of a zebrafish, which resembles a predator, and did not display a preference for yellow or red coloured fish images over control images. To test for the effects of embryonic ethanol exposure, zebrafish eggs were submerged in low concentrations of ethanol for a period of 2 hours at 24 hours post-fertilization and were tested during adulthood (4 months old onwards). Control and alcohol-exposed fish were placed in different behavioral paradigms that measured their responses to social and predator stimuli. It was found that zebrafish exposed to low doses of ethanol at 24 hours post-fertilization do not demonstrate robust differences in comparison to non-exposed control fish for any of the behaviors measured. Overall, the findings present zebrafish responses to various social stimuli, and suggest that low-dose ethanol exposure does not robustly affect social responses.
Optical Spectroscopy for Breast Cancer Risk Screening
Keywords: breast cancer
breast density
cancer risk
cancer screening
mammography
optical spectroscopy

Breast cancer (BC) has the highest mortality rate among women’s cancers worldwide, and incidence rates are rising in low- and middle-income countries (LMIC). Screening programs are well-established in most high-income countries, but there is much debate about screening frequency and the optimal screening ages. In LMIC screening infrastructure is insufficient. Optical spectroscopy (OS) can be used as a pre-screening technique to measure breast composition and predict mammographic density (MBD), a known BC risk factor. The goal of this thesis was to develop and evaluate an OS device which is portable, low cost and requires minimal operator interaction. The device was based on a research prototype used in previous studies, with two major changes: (1) a 13-laser-wavelength module replaced the broadband light source and (2) the source and detector positions were fixed within rigid holders of different sizes. The wavelengths critical for distinguishing between BC risk groups were selected using a principal components analysis of data from previous studies. Source and detector positions were chosen to match the optically-interrogated volumes of the original device via Monte Carlo simulations of photon propagation. Two versions were developed – one for women (the Cups device) and one for girls (the LEGACY device). The Cups device was evaluated in comparison with the research prototype on its ability to predict MBD. For both devices, women with high MBD could be identified from spectra with high sensitivity and specificity and correlation between mammographic percent density (MPD) and OS-predicted MPD was significant, although slightly weaker for the Cups device (r = 0.62 vs. r = 0.74). For girls, OS had been used as an objective method for distinguishing between breast development stages. Spectral analysis using only the wavelengths from the LEGACY device showed that the reduced spectral content does not affect the ability to distinguish between development stages.
Planning from "Table to Dump": Analyzing the Practice of Household Food Consumption and Food Waste in Urban Indonesia
Keywords: food consumption
food waste
Indonesia
infrastructure
planning
practice theory

By analyzing the ways in which diverse households shop, cook, consume, and waste, this dissertation reveals the complex relationship between space, class, and social relations in the generation of household food waste in Indonesia. Several themes are explored in four empirical chapters. First, a food waste regime conceptual framework is employed to better understand unequal power relations between "modern" food provisioning infrastructures such as supermarkets, and traditional food provisioning infrastructures, specifically in relation to space restriction and predatory pricing. Secondly, the food waste regime framework is also applied to examine the role of class and privilege in determining an individual's ability to define "what is food and what is waste" within the boundaries of the household. Thirdly, the application of the conceptual framework of "distancing" articulates the role of urbanization in the spatial and mental distancing of both the food supply chain and waste management infrastructure. Finally, from a statistical perspective, the dissertation examines whether income level and where people choose to shop (for example, the type of retail) impact the amount of household food waste generated in Indonesia. Using practice theory, planners are encouraged to take a closer look at different types of retail formats to understand how space may impact consumption. This study draws upon a qualitative study of 21 upper (n=7), middle (n=7) and lower (n=7) income households in Bogor, 12 key informant interviews with government officials, traditional food vendors, supermarket managers, and a waste collector, as well as the result of a quantitative study on 323 households. To conclude, this dissertation argues that there is a need to offer infrastructural support that can protect traditional food retail and promote more sustainable food waste management. Furthermore, considerations for social and environmental justice are key in the search for a systemic and dignified solution to the issue of food waste in Indonesia.