VictorJuiz/thesis huggingface dataset:
Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer
Keywords: lung cancer
Non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Global expression profiling of patient tumours has identified hundreds of genes controlling NSCLC progression and patient survival. Our laboratory previously identified a robust 15-gene prognostic signature predictive of NSCLC patient outcome. We hypothesized that these genes may contribute to malignant progression of lung cancer. This thesis probes the functions of three signature genes as a means to classify their expression changes as causal or responsive to NSCLC. In the first study, the signature gene L1CAM was found to promote both NSCLC metastasis and cell migration and invasion. This was supported by in silico analyses, which showed that L1CAM expression is consistently an independent prognostic factor in multiple large cohorts of NSCLC patients. The second study identified the signature gene TRIM14 as a putative NSCLC tumour suppressor. Loss of TRIM14 function increased in vitro proliferation and in vivo tumorigenicity of NSCLC cell lines. To exert its function, TRIM14 interacts with apoptosis-inducing factor possibly regulating its stability. The third study explored the efficacy of molecularly targeting prognostic biomarkers such as the signature gene MDM2 in primary tumour xenograft models of NSCLC. MDM2 inhibitors were found to effectively inhibit NSCLC tumour growth by activating the p53 tumour suppressor pathway and cell cycle arrest, confirming a role for MDM2 in the oncogenesis of NSCLC. Overall, these results demonstrate that prognostic gene signatures constructed using genomics approaches are a powerful tool to uncover genes having critical roles in lung cancer progression.
Factors Affecting Safety Performance of Construction Workers: Safety Climate, Interpersonal Conflicts at Work, and Resilience
Keywords: conflicts at work
individual resilience
organizational resilience
safety climate

A safety plateau in safety performance has been observed in many countries or regions. In order to continuously improve safety performance, the key is to identifying factors affecting safety performance. This research examined four factors, namely, safety climate, individual resilience (IR), interpersonal conflicts at work (ICW), and organizational resilience (OR) that may contribute to explaining safety outcomes. A self-administered survey was used. From 2013 to 2016, 1281 surveys were collected from 180 construction sites of Ontario, Canada. This thesis composed three papers, which leads to the following conclusions: • Safety climate not only affects physical safety outcomes but also employees’ job stress level. • ICW is a risk factor for safety performance. • IR has the potential to mitigate post-trauma job stress and interpersonal conflicts of construction workers. • Management commitment is the key to promoting a good safety culture. • Safety awareness is the most important individual factor affecting construction workers’ safety performance. • Team support, especially the support from coworkers, has a significant positive impact on construction worker’s safety awareness. Several original contributions were made: • This study designed and tested questions of individual resilience. • This study is the first empirical study investigating the impact of individual resilience on safety outcomes. • This study is the first study testing the antecedents of interpersonal conflicts at work and the resulting safety outcomes in the construction industry. • This study designed and tested organizational resilience questions in the context of construction industry. • This is the first study testing the mechanism about how the resilience factors interact with each other and eventually affect safety outcomes. • This study is the first study using structural equation modeling (SEM) to quantify organizational resilience. Accordingly, the following recommendations were provided: • Construction organizations need to not only monitor employees’ safety performance but also their psychological well-being. • Safety professionals may consider adding coping skill training programs to improve the individual resilience of their workforce and reduce conflict-related safety outcomes. • Construction organizations can improve employees’ safety awareness by promoting a good team-level safety culture, and by building a good reporting and learning culture.
Integrated Functional and Genomic Analysis of High-Grade Serous Ovarian Cancer
Keywords: cancer
CD151
genomics
high-grade
ovarian
rna interference

Epithelial ovarian cancer is the fifth-leading cause of cancer-related death for women in North America and is responsible for over 100 000 deaths/year worldwide (Ferlay et al., 2015). High-grade serous ovarian cancer (HGSC) is the most common and lethal subtype and the vast majority of women are diagnosed with advanced stage disease (Bowtell, 2010). The current standard treatment is aggressive surgery combined with adjuvant and/or neo-adjuvant platinum/taxane-based chemotherapy. Despite initial efficacy of standard therapy, resistant cancer recurs and 70% of patients die within 5 years after initial diagnosis (Bast et al., 2009). Further understanding of the molecular and cellular features that promote HGSC progression may assist in identifying new opportunities for therapeutic intervention and ultimately improve the prognosis of women with HGSC. My research has generated an extensive functional and genomic characterization of serous ovarian cancer cell lines and provides a framework for identifying vulnerabilities associated with distinct molecular features. Using this dataset, I have focused on the identification of genes encoding for highly expressed cell surface molecules. I have identified a novel role of the tetraspanin CD151 in serous ovarian cancer. I have found that CD151 depletion impairs survival, proliferation and tumor growth in murine models of a subset of HGSC cell lines. In search of the mechanism underlying CD151-dependency, I have uncovered a novel association for CD151-dependency in cancer cells with mesenchymal features. In particular, high ZEB1 and ZEB2 expression is tightly coupled with CD151-dependency and thus, may be used as biomarkers for stratifying tumors requiring CD151 for growth. Moreover, CD151-binding antibodies block the migratory capacity of CD151-dependent cells, thereby implicating CD151 in metastasis and dissemination of HGSC tumors. These studies provide a resource of characterized HGSC cell lines and suggest that CD151 may be a biological target in HGSC tumors.
Influence of Hydrodynamic Events on Circulation and Thermal Habitat in Coastal Embayments of the Great Lakes
Keywords: Internal waves
Modelling
Physical limnology
Resonance
Surface waves
Thermal habitat

Coastal embayments act as the main interface between urban and agricultural run-off and the waters of the Great Lakes. They make a large contribution to the water quality of the Great Lakes for their size. Given the relentless urbanization occurring in Ontario, it is now critical to understand how water circulation within these confined coastal bays determines the health of the aquatic ecosystem. This research tackles three interconnected aspects of embayment physics and littoral circulation. First, the mechanisms that contribute to the flushing of coastal embayments are assessed. Lake water level fluctuations provide an important role in flushing shallow coastal embayments in the Great Lakes, especially if the embayment has a resonant response. Specifically, long-period waves can excite resonance in coastal embayments, which greatly increases the flushing rates. Three shallow coastal embayments of Lake Ontario and Lake Huron are analyzed and the difference in their responses to similar long-period waves is found to be explained by resonance. Second, water stratification and its effect on the physical processes in coastal embayments is studied. Toronto Harbour, which is taken as a case study, is characterized by considerable thermal variability as a result of diurnal heat fluxes and large amplitude movements of the thermocline of Lake Ontario. During the ice-free period an array of benthic and surface temperature loggers were deployed to obtain the spatio-temporal distribution of water temperatures. Cold intrusions were found to quickly flow from the lake into the harbour and lead to rapid drops in temperature that may be associated with a variety of negative effects on many aquatic organisms. Finally, frequent water level oscillations are shown to drive significant exchange between Toronto Harbour and Lake Ontario. Analysis of water currents, water levels and temperatures is used to determine the hydrodynamic characteristics of the lake-harbour system and demonstrate that strong water level fluctuations with a period of one-hour dominate the exchange flows in the shallow embayments of the harbour, which is in contrast to the conventional wisdom that water circulation in coastal embayments of the Great Lakes is always dominated by baroclinic processes driven by differential heating or upwelling events.
Impacts of Climate Variability and Change on Eastern North Pacific Tropical Cyclones
Keywords: eastern North Pacific basin
El-Nino Southern Oscillation
sea surface temperature
tropical cyclone
western development region

Damages inflicted by tropical cyclones (TCs) worldwide have increased in recent decades with climate change and variability playing key roles in altering TC characteristics. In this thesis, the impact of natural variability is explored, using ENSO conditions, and climate change on the nature of eastern North Pacific (ENP) TCs. The first research objective of the thesis focused on a spatial-temporal separation of ENP storms based on El Niño-Southern Oscillation (ENSO) phase (temporal variability, El Niño, La Niña, neutral) and regional storm stratification (spatial variability, east and west). The western development region (WDR) storms were found to be more sensitive to influences of ENSO. In particular, during El Niño years, there were more WDR storms. The second research objective explored the ENSO impact on the trajectory of ENP storm tracks by examining the locations for genesis and downgradation points and storm track movements. The storm tracks were strongly influenced by ENSO phases, with significant differences detected for many ENSO pairings. However, when storm data are regionally separated the latitudinal movement of WDR storms tend to be more extensive during El Niño conditions and as a result there are more landfalling TCs. The third research objective of the dissertation explored the importance of near-time sea surface temperatures (SSTs) on storm intensities. SST thresholds were found that were critical for the sustenance of stronger ENP storms that achieve hurricane and major hurricane status. Significantly, the minimum SST threshold varied between the MDR subdivisions. For major hurricanes, the SST requirements for EDR and WDR are substantially lower than that found in the North Atlantic basin at 28.25°C. Although SSTs appear to contribute little in determining the ultimate maximum storm intensity for ENP storms in general, when ENP storms are regionally divided, SSTs are found to be highly associated with the WDR major hurricanes. Evidently the recent warming shown in the distribution of storm-bounded SSTs has led to the rise of maximum potential intensity for ENP storms. Overall, the common theme that emerged from these three studies is that ENP storm characteristics associated with WDR are inherently more sensitive to climate variability and change.
Projecting the Influence of Climate Change on Extreme Ground-level Ozone Events in Selected Ontario Cities
Keywords: Canada
Climate change
Extreme tropospheric ozone
Ontario
Statistical downscaling
Urban smog

Ground-level ozone (O3) is perhaps one of the most familiar pollutants in Ontario, Canada because it is associated with most smog alerts in the province. O3 varies on a number of spatial and temporal scales, primarily due to meteorological variability and the impact of long-range transport of its precursors on the photochemical processes. The goal of this thesis is to project the change in the probability of occurrence of future Extreme Ground-level Ozone Events (EGLOEs) due to changes in atmospheric conditions as a result of climate change for cities located in the southern, eastern and northern parts of Ontario, Canada by using a combination of General Circulation / Global Climate Models (GCMs) and statistical downscaling. These Ontario cities are Toronto, Windsor, London, Kingston, Ottawa, Thunder Bay, Sudbury and North Bay. The successful downscaling method used in this research to generate city-specific climate change scenarios was the Statistical DownScaling Model (SDSM) version 4.2.2, which is a hybrid of regression-based and stochastic weather-generator downscaling methods. The results indicate that the mean values of the daily maximum ground-level ozone concentrations could increase by up to 12 – 17% in Southern Ontario, 8 – 16% in Eastern Ontario and 1.5 – 9% in Northern Ontario by the end of the century due largely to changes in long-range transport. Three important themes emerge from the results: 1) the research successfully model O3 concentration in a region where long-range transport plays a substantial role. 2) The clear confirmation regarding the role of long-range transport in determining O3 concentration in most areas of Ontario. 3) The projected increase of ozone in Ontario, due largely to an increase of long-range transport, caused by shifting atmospheric dynamics rather than a direct temperature effect on ozone production. Moreover, the results indicate that the future Southern, Eastern and Northern Ontario’s EGLOEs with the O3 concentration ≥ 80 ppb (the current Ontario 1-hour Ambient Air Quality criterion for extreme ozone concentration) will have an increase of over 60%, 50% and 62% respectively by the year of 2100 under the different future scenarios in the third version of the Coupled Global Climate Model (CGCM3) and the Hadley Centre’s Climate Model (HadCM3).
Story of Brominated Flame Retardants: Substance Flow Analysis of PBDEs from Use to Waste
Keywords: Flame retardants
PBDEs
products
Substance flow analysis
Use phase
Waste phase

The main goal of this study was to understand the fate of brominated flame retardants (BFRs), particularly PBDEs, during the life cycle of BFR-containing products. PBDEs were added to the Stockholm Convention list of chemicals to be eliminated. The migration of BFRs from products and their partitioning to dust results in human exposure through dust ingestion and inhalation. Moreover, during the use of BFR-containing products, direct contact with these products can lead to human exposure. With the proliferation of BFRs as PBDE alternatives, identifying the product source of these chemicals is essential to minimize the risk associated with the exposure. In this research, a rapid and non-destructive method was developed to identify and to some extent quantify BFRs used in consumer products. The next step towards the management of these chemicals is to estimate the time course by which these chemicals will remain in use. Based on consumption patterns of PBDE-containing products, the time-dependent stock of PBDEs contained in in-use products was estimated for the U.S. and Canada from 1970 to 2020. Considering only the first lifespan of products, the stock of PBDEs was estimated to be ~120,000 t in 2014 and it is estimated that by 2020, ~ 60% of this stock will remain in products in the use phase. Although the flow of PBDE-containing products to the waste phase started to decline following 2008, this flow will continue as these products reach their end of life and enter the waste phase. As these products leave the first use phase, their accumulation in storage and waste phases will continue to act as sources of PBDEs to the surrounding environment with annual emission rate of 0.3-4 tonnes路y-1 between 1970 and 2020. Thus, the management of BFR-containing products deserves more attention as the mismanagement of these products, especially waste electronics, has led to undesirable and irreversible global environmental consequences. The results of this dissertation suggest that current waste management programs in the U.S. and Canada are challenged to deal with influx of e-waste in the near future.
Towards the Development of Techniques to Facilitate the Assembly and Characterization of Quantum Dot— Gold Nanoparticle Complexes for Resonance Energy Transfer Based Assays
Keywords: DNA
Energy transfer
Gold nanoparticle
Monovalent conjugates
Nanoparticle quantification
Quantum dot

Resonance energy transfer between quantum dots and gold nanoparticles represents one of the most popular transduction schemes for biosensors using multi-nanoparticle complexes. This thesis investigates the influence of quantum dot positioning, relative to the gold nanoparticle, on the analytical performance of these assays. Stoichiometric assembly of the quantum dot-gold nanoparticle complexes required accurate knowledge of the quantum dot concentration. A technique was developed to quantify the molar concentration of nanoparticles in solution. This technique relied on the quantitative analysis of the statistical distribution of nanoparticle-ligand conjugates that form when nanoparticles are functionalized with small equivalents of ligand. The technique was successfully validated using gold nanoparticles, and was subsequently applied to determine the concentration of the alloy quantum dots. The precise positioning of the quantum dots relative to the gold nanoparticles required monovalent conjugates of the quantum dots. These were prepared using a magnetic bead based technique where positively charged magnetic beads were used to capture and selectively isolate the monovalent quantum dot-DNA conjugates. Successful isolation of monovalent conjugates was confirmed using single molecule fluorescence spectroscopy and the monovalent conjugates were found to retain their activity as determined using quantitative hybridization assays. Optimizing the quantum dot-gold nanoparticle assay required the investigation of two different configurations of nanoparticle arrangement. The first involved arranging quantum dots around a gold nanoparticle core, while the second involved arranging gold nanoparticles around a quantum dot core. The first configuration was found to have optimal analytical performance, as evaluated using quenching efficiencies and influence of inner filter effect. The ability to arrange multiple quantum dots around a single large gold nanoparticle minimized the negative influence of the inner filter effect, while the high quenching efficiency ensured high responses to target hybridization.
Fluctuation Analysis of Oxidation-Reduction Potential in Circumneutral pH Iron-Oxidizing Microbial Systems
Keywords: biosignature
detrended fluctuation analysis
iron-oxidizing bacteria
oxidation-reduction potential

The goal of this thesis was to assess the utility of using small-scale fluctuations in oxidation-reduction (redox) potential to distinguish microbial from chemical iron oxidation. Fluctuations in potential arise from the motion of particles in a fluid; measuring fluctuations is therefore a system-scale observable property of micro-scale chemical behaviour, as such particle motion constitutes diffusion. Fluctuations are described by the strength of their correlation, as measured by scaling exponents. A method for the calculation of scaling-exponents of long-range correlation in redox potential measurements was developed, including new instrumentation and the modification of an existing physiological processing algorithm for use with environmental microbiological data sets. Steady-state biological and chemical systems were compared, and scaling exponents calculated from each system were found to differ significantly. In a final study, a series of microcosms were used to determine the relationship between scaling exponent, measuring correlation strength, and oxidation rate. The biological systems are governed by the rate of reaction, while the chemical systems appear to be diffusion-controlled. Because in these systems, Fe(II) is a metabolite, redox potential can then be interpreted as a physically-constrained proxy for metabolic activity. This allows the characterization of biological activity in situ.
Dis-placing the Prison: Carceral Space, Disposable Life, and Urban Struggle in Neoliberal America
Keywords: carceral state
geography
neoliberalism
prison
surplus life
urban

This dissertation contributes to the emerging field of carceral geography by demonstrating how carceral space produces and manages social disposability in late capitalist American life. In so doing, it posits that carceral space must be conceived as a complex geography, one that inscribes the production of racialized poverty, incarceration, and devalued life into its everyday socio-spatial relations. Carceral space encompasses the whole chain of relationships that make up the prison system: from the sites of criminalization, arrest and conviction to the landscapes of building construction; from edifices of captivity to the spaces deployed for the circulation and transfer of bodies. Carceral space also, I argue constitutes those social relations and geographic practices through which the stateâ s capacities of containment, displacement and dispossession are put to work for racial capitalism. The dissertation examines several illustrative carceral spaces at different points along the continuum of penal coercion in order to answer the question: How does carceral space help produce and manage social disposability? Using qualitative methods, including in-depth interviews, ethnographic participant observation, and textual analysis, my four case studies demonstrate that the production of disposability is an active process, spatialized in a range of places and forms that are politically mutable, highly contested, and differentially experienced. Throughout my case studies, geographies of spatial isolation and individuation function alongside the neoliberal logic of individual responsibility, to undermine black sociality and the forging of collective counter-power to racial capitalism and the carceral state. I argue that the racialized production of the â criminalâ provides powerful legitimizing cover for the making and social differentiation of surplus populations. The criminal is a paradigmatic category of disposability in capitalist liberal democracies precisely because the project of neoliberalism makes it so hard to divest from the economy of individualized responsibility and accountability. Finally, the dissertation points to some of the ways in which the capacities of the carceral state are being retrofitted for the current political-economic conjuncture, producing new spatial fixes for managing surplus life under the pretext of penal reform. I conclude that so long as the actual social relations for which the carceral state is put to work remain unchallenged, the spatial organization of racialized unfreedom and surplus life remain a pressing and pernicious threat.