English

Neuroblastoma (NB) has one of the highest mortality rates in pediatric oncology due to relapsed and refractory disease. Current aggressive multi-modal treatments are inhibited by dose-limiting toxicities and are associated with late-effects and secondary malignancies, emphasizing the necessity for novel therapeutics. Uniquely, most NB cells highly express disialoganglioside (GD2) a cell surface glycolipid that can provide a target for tumour-specific delivery. This study demonstrates a comprehensive evaluation of silver nanoparticles (AgNPs) and the first preliminary evaluation of anti-GD2-AgNP antibody-drug conjugates (ADCs) against NB in vitro. This present study validates the potential for AgNPs as an anti-cancer agent against NB as AgNPs demonstrated preferential toxicity towards NB cells through metabolic inhibition and indicative morphological alterations, while a less tumorigenic cell line demonstrated resistance to AgNP treatment. Therefore, this work identified an AgNP cell-type-dependent cytotoxicity effect. Low conjugation efficiency of the anti-GD2 monoclonal antibody, 14.G2a, to NHS-activated AgNPs failed to exert greater toxicity than the AgNPs alone. Collectively, this thesis provides novel information regarding the anti-cancer effects of AgNPs against NB with recommendations for anti-GD2-AgNP ADCs.

Author Keywords: ADC, Chemotherapy, GD2, Neuroblastoma, Silver nanoparticles

Salamanders are capable of tissue regeneration throughout all life-stages, which requires the dedifferentiation of mature cells to regrow lost tissues. Dedifferentiation is promoted by degradation of the extracellular matrix by matrix metalloproteases, as well as lysosomal degradation of intracellular and cell-surface proteins that mark cells as part of a mature lineage. Salamanders are also capable of developing cannibalistic phenotypes, plastic traits that are elicited by environmental stressors that result in elevated circulating glucocorticoid (e.g., corticosterone) levels that underlie many fundamental adaptive changes in morphology. Interestingly, the direct effect of corticosterone on regeneration and the cannibalistic phenotype have yet to be examined. In the present thesis, axolotls (Ambystoma mexicanum) were exposed to exogenous corticosterone and 50% of the distal tail tissue was removed. The effects of high corticosterone levels on matrix metalloprotease (MMP-2, MMP-9) and lysosomal acid phosphatase (LAP) activity were assessed; these are two classes of enzymes which are markers of extracellular matrix and intracellular remodeling during regeneration, respectively. We found that elevated corticosterone levels inhibited tissue regeneration, by prolonging the dedifferentiation phase as indicated by increased LAP and reduced MMP-2 and MMP-9 activity. Elevated corticosterone levels also promoted the cannibalistic morphology and this effect was strongest among smaller individuals.

Author Keywords: amphibian, cannibalistic morphology, corticosterone, dedifferentiation, regeneration, stress

Media has had a significant influence on how individuals living with and at risk of Human Immunodeficiency Virus (HIV) care for their health. This research builds on previous research to explore the link between HIV related media messaging and HIV related health behaviours using a mixed methods approach. To investigate the access to and perceptions of HIV related media, a sample of 129 individuals took part in an online survey and 13 were assessed in follow up semi-structured interviews. People living with HIV, people at risk of HIV, and participants not in those groups differed on a number of HIV media access variables, including the amount of time spent interacting with HIV related media, how they accessed it, and its perceived effects on their HIV related attitudes and behaviours. Interviews explored these differences more, finding that while current HIV related media is less stigmatizing and more factual than the past, most current HIV related media is distributed via social media and is accessed by a relatively small group of HIV specialist viewers. The history of HIV related media continues to play an important role in determining perceptions of HIV related media. Implications of this study will inform strategies for the communication of HIV health messages.

Author Keywords: AIDS, HIV, Media and Health, Mixed Methodology, Social Determinants of Health, Social Media

Numerous prey taxa employ defensive postures for protection against attack by predators. Defensive postures mitigate predation risk at various stages of the predator-prey sequence, including through crypsis, mimicry, thanatosis, aposematism, and deflection. In terrestrial salamanders, defensive postures may be aposematic, or deflect attacks away from vital body parts and towards the tail, however the extent to which these strategies act exclusively or synergistically remains poorly understood. Herein I demonstrate a novel approach to study the function of salamander defensive postures through experimental manipulation of predator response to antipredator behaviour in a natural field setting. I deployed 1600 clay salamander prey on Pelee Island, Ontario, manipulating prey size (small, large) and posture (resting, defensive) and documented attack rates across three predator types to further assess the effect of prey body size and predator type on antipredator efficacy. My research suggests that irrespective of prey body size, defensive posture does not function through aposematism, but rather acts to deflect predator attacks to the tail, which is commonly noxious and expendable in terrestrial salamanders. An intriguing possibility is that this behaviour facilitates taste-rejection by predators. Overall, my research should further contribute to our understanding of the importance and potential evolutionary significance of defensive posturing in Ambystoma salamanders, and more broadly, on the determinants of prey vulnerability to predation. I also briefly discuss the implications of my results to the conservation of Ambystoma populations on Pelee Island.

Author Keywords: Anti-predator behaviour, Aposematism, Attack deflection, Predator avoidance, Small-mouthed salamander, Taste-rejection

Chemical presumptive tests are used as the primary detection method for latent bloodstain evidence. This work focuses on developing a forensic blood substitute which mimics whole blood reactivity to a luminol solution commonly used in presumptive testing. Designing safe and accessible materials that mimic relevant properties of blood is a recognized research need in forensic science. Understanding the whole blood dynamics related to reactivity with presumptive testing chemicals is important for developing accurate analogues. Provided in this thesis is a quantitative and qualitative characterization of photoemission from the reaction of a luminol solution to ovine blood. Luminol reactivity of a horseradish peroxidase encapsulated sol-gel polymer was validated against this ovine blood standard. This material, the luminol-reactive forensic blood substitute, is a key deliverable of this research. An optimized protocol for implementing this technology as a reagent control test, and as a secondary school chemistry experiment are presented. This thesis outlines the research and development of a forensic blood substitute as it relates to presumptive testing in bloodstain pattern analysis.

Author Keywords: bloodstain pattern analysis, forensic science, luminol, presumptive testing, secondary school education, sol-gel chemistry

Aeolian transport of sand particles is an important geomorphic process that occurs over a significant portion of the earth's land surface. Wind tunnel simulations have been used for more than 75 years to advance the understanding of this process; however, there are still several principles that lack validation from direct sampling of the sand particles in flight. Neither the three-dimensional dispersion of, nor the momentum carried by particles in flight have been properly measured. This has resulted in the inability to validate numerical particle dispersion models and the key boundary-layer momentum partitioning model that serves as the framework for understanding the air-sand feedback loop. The primary impediment to these measurements being made is a lack of tools suited for the task. To this end, this PhD aims to improve existing particle tracking technology, thus enabling the collection of particle measurements during wind tunnel experiments that would address the aforementioned knowledge gaps.

Through the design and implementation of the Expected Particle Area Searching method, a fully automated particle tracking velocimetry system was developed with the capability to measure within ½ grain diameter of the bed surface under steady state transport conditions. This tool was used to collect the first 3-D data set of particle trajectories, from which it was determined that a mere 1/8th of sand transport is stream aligned and 95% is contained within ± 45o of the mean wind direction. Particles travelling at increasing spanwise angles relative to the stream aligned flow were found to exhibit different impact and ejection velocities and angles. The decrease in the number of particles with increasing height in the saltation cloud, very close to the bed is observed to transition from a power to a linear relation, in contrast to previous literature that observed an exponential decay with coarser vertical resolution.

The first direct measurements of particle-borne stress were captured over a range of wind velocities and were compared with earlier fluid stress measurements taken using Laser Doppler Anemometry. In support of established saltation theory, impacting particle momentum is found to contribute strongly to particle entrainment under equilibrium conditions. In opposition to established theory, however, particle-borne stress was found to reach a maximum above the surface and does not match the change in air-borne stress with increasing distance from the surface. Near surface splashed particles, measured herein for the first time, appear to play a greater role in stress partitioning than previously thought. This study suggests that research is needed to investigate the role of bed load transport on stress partitioning, to differentiate between airborne trajectory types, and to develop particle tracking tools for field conditions.

Author Keywords: Aeolian Transport, Eolian Transport, Particle Tracking Velocimetry, Saltation, Stress Partitioning, Wind Tunnel Simulation

The Kentucky coffee tree (Gymnocladus dioicus) is an endangered tree species native to the American Midwest and Southwestern Ontario. Significant habitat loss and fragmentation due to agricultural, industrial and urban development has caused gradual decline across its native range. The aims of this study were to investigate: (1) patterns of genetic diversity and, (2) genetic differentiation (3) relative levels of sexual vs. clonal reproduction, and (4) potential for reduced genetic diversity at range edge for wild G. dioicus populations. An analysis of variation at nine microsatellite loci from populations in the core of the species distribution in the U.S.A. and 4 regions of Southwestern Ontario indicated that G. dioicus has remarkably high genetic similarity across its range (average pairwise FST= 0.05). Germination trials revealed that the seed coats require highly invasive treatments (e.g. 17.93 mol/L H2SO4) to facilitate imbibition, with negligible germination observed in treatments meant to emulate prevailing conditions in natural populations. Low levels of sexual reproduction, high genetic similarity, and habitat degradation are issues that exist across the entire native range of G. dioicus.

Threats such as climate change and increased anthropogenic activity such as shipping, are expected to negatively affect the Arctic. Lack of data on Arctic systems restricts our current understanding of these sensitive systems and limits our ability to predict future impacts. Lakes and ponds are a major feature of the Arctic landscape and are recognized as 'sentinels of change', as they integrate processes at a landscape scale. A total of 1300 aquatic sites were assessed for common chemical and physical characteristics. Geology type was found to be the greatest driver of water chemistry for Arctic lakes and ponds. Acid-sensitivity was assessed using the Steady State Water Chemistry model and a subset of 1138 sites from across the Canadian Arctic. A large portion of sites (40.0%, n = 455) were classified as highly sensitive to acidic deposition, which resulted in a median value of 35.8 meq·m―2·yr―1 for the Canadian Arctic. Under modelled sulphur deposition scenarios for the year 2010, exceedances associated with shipping is 12.5% (n = 142) and 12.0% (n = 136) for without shipping, suggesting that impacts of shipping are relatively small.

Author Keywords: Acidic deposition, Arctic lakes, Critical loads, Shipping emissions, Steady-State Water Chemistry Model, Water chemistry

This thesis explores Frankenstein's popular culture narrative, contrasting recent Frankenstein texts with the content of Mary Shelley's classic novel and James Whale's iconic films Frankenstein (1931) and The Bride of Frankenstein (1935). The research investigates how Frankenstein's legacy of adaptations function intertextually to influence both the production and the consumption of Frankenstein texts, referring to this complicated and contradictory intertextual web as "the Composite Frankenstein."

This thesis present the Composite Frankenstein as a hermeneutic by which to view Frankenstein's collaborative and cumulative identity in popular culture, drawing on the work of other scholars on adaptation and intertextuality. Sarah Milner investigates the context of the key Frankenstein texts, the novel and the 1931 film; this research's goal is to destabilize the perception of authorship as an individual's mode of production and to investigate the various social processes that influence text creation and consumption.

Author Keywords: adaptation, authorship, Frankenstein, intertextuality, James Whale, Mary Shelley

I assessed how organisms having multiple biotic attributes may have conflicting niche determinants, and whether the realized niche reflects single or multiple attributes. All-female salamanders engage in two biotic states: hybridism and reproductive parasitism. Hybrids should occupy areas transitional to those used by parental species, whereas parasites that engage in competition with hosts should occupy habitats moderately suitable for hosts. Using niche models, I predicted realized niches for unisexual Ambystoma via a hybrid model (environmental predictors) and a parasite model (host suitability predictors). The hybrid model predicted that the unisexual niche would indeed be transitional between parental Ambystoma spp. The parasite model demonstrated unisexual salamanders occupied habitats moderately suitable for hosts, though model validation did not fully corroborate its predictive power. The hybrid model was more descriptive of unisexual occurrence than the parasite model. When species have competing ecological roles a primary biotic attribute may largely derive the realized niche.

Author Keywords: Ambystoma, hybrid, niche, parasite, range, unisexual