VictorJuiz/thesis huggingface dataset:
The Effects of Surface Anisotropy on Reaction Dynamics
Keywords: Density Functional Theory
Reaction Dynamics
Scanning Tunneling Microscopy
Surface Aligned Reactions
Surface Chemistry
Surface Science

Reaction dynamics of meta-diiodobenzene (mDIB) and trifluoromethyl (CF3) was studied on the anisotropic Cu(110) surface at 4.6 K using Scanning Tunneling Microscopy (STM). Both systems were modeled by Density Functional Theory (DFT). The surface anisotropy, given by rows of Cu-atoms along the [11 ̅0] direction, was found to give three previously unreported outcomes: product rotation, bond-selectivity, and ‘surface-molecular-beams’. In the electron-induced reaction of mDIB, iodophenyl product rotation was observed following single C-I bond dissociation in the major pathway. The rotation was shown to be caused by the attraction between the I-atom of the iodophenyl and the raised Cu-rows. In a minor pathway both C-I bonds were broken concurrently to give I-atoms from an un-rotated mDIB attributable to short iodophenyl lifetime. Since the extent of the iodophenyl rotation correlated with its rotational lifetime, the observed rotation could be used with the aid of theory to ‘clock’ the reaction dynamics. Bond-selectivity was observed in the C-I electron-induced dissociation of physisorbed mDIB. The C-I bond directed along the Cu-row was found to dissociate with a hundred-fold greater probability than the C-I directed across the Cu-row. This large bond-selectivity was due to the added electron impulsively propelling the system towards a lower energy barrier when the C-I bond was directed along the Cu-row, in which case C-Cu attraction stabilized the transition state. Novel ‘surface-molecular-beams’ of a difluorocarbene (CF2) ‘projectile’ were generated from the electron-induced dissociation of CF3. In the beams the CF2 projectile traveled unidirectionally along a Cu-row as far as ~50 Å, by translation-rotation coupling analyzed as ‘ratcheting’. In further work the CF2 ‘projectile’ was aimed at a stationary CF2 ‘target’ with selected impact parameter, and collision energy. At zero impact parameter and high collision energy the C2F4 product was formed recoiling ‘forward’, due to retention of translational energy along the direction of the incoming projectile. At low collision energy the C2F4 product recoiled ‘backward’, due to association reaction catalyzed by a raised surface Cu-atom.
c-Src Controls Mouse Embryonic Osteogenic Differentiation Through Regulation of Stat1 Stability
Keywords: Bone
Differentiation
Embryonic stem cells
Runx2
Src
Stat1

The protein tyrosine kinase Src is expressed ubiquitously and is involved in differentiation. However, the role of Src in osteogenic differentiation is complex since it has been reported to function both as repressor and activator. Using the small molecule inhibitor PP2, c-Src specific siRNAs, and tet-inducible lentiviral vectors overexpressing constitutively active c-Src, I confirmed c-Src inhibitory role in mouse embryonic stem cells (mESCs) and mouse preosteoblast MC3T3-E1s osteogenic differentiation. I further predicted that the increased level of osteogenic differentiation is regulated through Runt-related transcription factor 2 (Runx2). Additional analysis revealed that active c-Src (p-Y416-c-Src) lowers Runx2 nuclear localization and transcriptional activity in mESCs without having any effect on Runx2 expression level. I provide the first evidence linking inhibitory role of c-Src to Runx2 subcellular localization through signal transducer and activator of transcription 1 (Stat1), the cytoplasmic anchoring partner of Runx2. I discovered that higher level of active c-Src increases Stat1 protein half-life by inhibiting Stat1 proteasomal degradation. Therefore, by inhibition of c-Src activity, Stat1 protein level is reduced resulting in less of interaction with Runx2. This in turn increases nuclear localization and transcriptional activity of Runx2. Collectively, my study has defined a new mechanism, by which c-Src activity inhibits transcriptional regulation of osteogenesis.
Anoxia-Mediated Electrical Suppression in the Cerebral Cortex of the Western Painted Turtle (Chrysemys picta bellii): Role of the Mitochondrion
Keywords: Anoxia tolerance
Channel arrest
Mitochondria
Spike arrest
Stellate neurons
Western painted turtle

The vertebrate brain is one of the most oxygen-demanding organs of the body. In animals that are intolerant to severe hypoxia or anoxia, the brain undergoes irreparable harm within minutes of insufficient oxygen supply. The western painted turtle (Chrysemys picta bellii) has evolved the ability to survive winter months without access to air and does not experience any apparent neurological damage. It is able to achieve this by reducing energetically-demanding cellular processes and the overall electrical activity of the brain to match the reduction in energy availability, effectively balancing energetic supply and demand during anoxic periods. The aim of my research was to understand how the signal of lowered oxygen tension is translated to a reduction in electrical activity with specific focus on the involvement of mitochondria, which are oxygen-consuming organelles that provide the cell with energy in the form of adenosine triphosphate (ATP). Since mitochondria are functionally associated with oxygen availability, I hypothesized that mitochondria serve as oxygen sensors in the anoxia-tolerant brain and initiate signaling cascades that ultimately reduce energy consumption. In the following body of work, I demonstrated that: 1) anoxia leads to depolarization of the mitochondrial membrane potential, which is required for mitochondrial calcium release and glutamatergic channel arrest, and occurs via ATP-sensitive potassium channel opening balanced by proton efflux via the ATP synthase; 2) the mitochondrial depolarization event occurs independently of the enzyme protein kinase C epsilon; and 3) the anoxia-mediated reduction in mitochondrially-derived reactive oxygen species results in increased activity in fast-spiking GABAergic interneurons and elevated extracellular [GABA]. Together, this research contributes to our understanding of neuroprotective mechanisms in anoxia-tolerant organisms and demonstrates the importance of mitochondrial function during the early phases of the anoxic response.
Trunk Function and Ischial Tissue Health in Spinal Cord Injury
Keywords: Pressure Injuries
Reaching
Sitting
Spinal Cord Injury
Trunk function
Ultrasound imaging

Pressure injuries are a common secondary complication following spinal cord injury (SCI). Since individuals with SCI have sensorimotor impairments, they neither can feel pain associated with tissue damage due to prolonged unrelieved pressure nor are able to prevent pressure injuries due to mobility impairments. Deep tissue injury is a form of pressure injuries that occurs in the muscle and subcutaneous tissue before tissue breakdown appears at the skin surface. This thesis attempted to address four research questions pertinent to deep tissue injury and offloading in individuals with SCI. First, we proposed a quantitative ultrasound imaging approach to characterize the integrity of the tissues overlying the ischial tuberosity. We demonstrated that the thickness and gray scale measures of the skin, subcutaneous tissue and muscle has potential to be used as a tissue health monitoring approach. The second study investigated our ability to assess trunk strength and function using the multidirectional reach test. This study demonstrated that monitoring changes in trunk strength and reach distance could be used to assess trunk function in individuals with SCI. The third prospective cross-sectional study aimed at determining if there is a relationship between trunk function and offloading of the ischial tuberosities in individuals with SCI. We discovered that trunk strength was significantly higher in people who were able to Reach compared to Non-Reachers, and that offloading times over the ischial tuberosities were lower in Non-Reachers vs. Reachers. Regardless of an individual’s ability to engage in a reaching task, participants with SCI spent more time offloading the left ischial tuberosity compared to the right ischial tuberosity. The fourth exploratory prospective cross-sectional study compared thickness and texture measures of tissue overlying the ischial region in able-bodied vs. SCI participants. We discovered that the area occupied by muscle was significantly greater in the SCI participants when compared with the able-bodied cohort. Individuals who did not engage in offloading had more homogenous skin, subcutaneous tissue and muscle. These studies represent the first step towards better understanding the relationships between offloading, trunk function and health of tissue overlying the ischial tuberosity in SCI population.
Characterization and clinical applications of textile-based sensors in rehabilitation
Keywords: assistive technology (AT)
augmentative and alternative communication (AAC)
e-textiles
rehabilitation

The focus of much previous research and development in electronic textiles has been on remote sensing and monitoring, while opportunities for textile-mediated feedback to the wearer remained unexplored. Additionally, feasibility with clinical populations had not been reliably demonstrated. This thesis explores validation and clinical testing of fabric- and thread-based mechanical and electrical sensors. While conductive thread-based stretch sensors have been previously described in terms of their overall correlation with existing measurement modalities, the ability of such sensors to predict linear elongation had yet to be investigated. In a characterisation study, we developed an algorithm to predict linear elongation, given sensor resistance. Sensors based on the 5-thread coverstitch predicted linear elongation to within 5% of sensor range. Given the possibility of applying stitched sensors non-destructively to existing garments, further study of these sensors remains worthwhile. In a study combining sensor characterisation and clinical testing, we designed and tested a wearable speech generating device (SGD) incorporating resistive textile-based switches for a nonverbal pediatric participant with vision impairment. In mechanical tests, the best performing textile switch consisted of two layers of woven conductive fabrics and one layer of insulating felt. In testing the SGD with a pediatric participant, communicative interactions were found to be higher with the fabric-based SGD, particularly at school. Tactile differentiability of keys, device wearability, and aesthetic and functional personalization may be promising advantages of fabric-based SGDs for pediatric users. While electrooculography (EOG) is a promising technology for access for individuals with communication disabilities, traditional sensors can be uncomfortable and obtrusive. We therefore explored the use of fabric-based electrodes for measuring EOG in two participants with neuromuscular disabilities. We developed a peak detection algorithm which differentiated blinks based on relevant peak characteristics (peak height, prominence, and width) with minimal training. Results were promising in both participants, with 83–87% precision and 85–86% recall for online sessions. While thread- and fabric-based sensors have demonstrated efficacy for unobtrusive monitoring in healthcare and rehabilitation applications, additional uses in interaction and communication are promising and warrant further exploration.
“Great Powers yet Unsuspected in Them”: The Insurrection of Things in Victorian Fiction
Keywords: domestic interior
identity formation
imperialism
novels
thing theory
Victorian

This dissertation explores how Victorian concepts of subject formation resulted in the concomitant creation of “things” as a separate entity from objects: entities that, unlike objects, with their socially-encoded transparency, exhibit a radical alterity that resists systems of containment and cognition. A pervasive cultural fear of insurrectionary things is evident in the era’s most popular literary form, the novel—a genre closely tied to its notions of identity construction. Characters’ unease around ostensibly inert objects arises from the culture’s fantasy of a material world populated with matter that can be acquired, arranged, and manipulated to maintain “traces” of its owner. But if personality can inflict itself upon objects, what prevents objects from permeating personality? Historically contextualizing my close readings with guidebooks, magazines, travelogues, and home décor manuals, in this project I demonstrate that the era’s discourse of thinghood arises from an ontologically imperialistic and intensely fragile concept of a “territorialized” identity, both personal and national. My introduction describes the cultural conditions under which Victorian human-object relations developed and explains how the novel both established and problematized the fusion of person and thing. My first chapter examines Dickens’s brief hope that the newly formed Detective Police could sort out the ontological chaos of London, shedding light on the peculiar activities of Inspector Bucket in Bleak House. The next two chapters focus on the domestic interior as the problematic seat of Victorian identity: Charlotte Brontë’s Jane Eyre and Charlotte Perkins Gilman’s “The Yellow Wall-paper” use conventionally gothic motifs to expose how home design restrained women’s ability to construct autonomous selves, while Joris-Karl Huysmans’s À rebours and Oscar Wilde’s Picture of Dorian Gray display queer forms of identity formation based on a permeable relationality with the world. The final chapter examines depictions of African statues, both factual and fictional, to uncover a late-imperial “rhetoric of thinghood” used to mark and reject objects whose social histories conflict with Eurocentric ideas of human development. This dissertation relies on “thing theory” throughout to unpack the psychological and phenomenological triggers underpinning the era’s oppositional human-object interactions, which infused “things” with much of their assertive metaphysical presence.
Investigating the Intersection of Nickel and pH in Helicobacter pylori through the HpNikR Transcription Factor
Keywords: Acid Adaptation
Helicobacter pylori
Nickel
Transcription Factor

Helicobacter pylori is a pathogenic bacterium that colonizes the human stomach. To survive its acidic environment, H. pylori synthesizes large quantities of the nickel-containing urease enzyme, which hydrolyzes urea into ammonia to neutralize the local environment of the cell. The importance of nickel to the survival of H. pylori is counterbalanced by the cytotoxicity of nickel, and the nickel-responsive HpNikR transcription factor helps maintain this balance by regulating a variety of genes in H. pylori in response to elevated nickel concentrations. Previous evidence also suggested that HpNikR can also bind DNA in a pH-responsive manner, but the biological relevance of this observation was unclear. In this work, the nickel-responsive regulon of HpNikR was probed, and two novel targets of nickel-dependent repression by HpNikR in vivo were identified. The pH-responsiveness of HpNikR was also explored, and cytosolic pH measurements confirm that the cytoplasm of H. pylori becomes sufficiently acidic to trigger pH-dependent DNA binding by HpNikR when the bacteria are exposed to pH 2 conditions. This drop in cytosolic pH allows HpNikR to regulate several genes in the acid adaptation pathway in a pH-dependent manner, including ureA and amiE. Biochemical characterization of an isogenic H. pylori ΔnikR strain revealed that HpNikR is important for the survival of H. pylori undergoing severe acidic shock, and that the loss of viability in the ΔnikR strain is not because of over-acidification of the cytoplasm. The network of gene regulation in H. pylori is very complex, and understanding the role that HpNikR plays during acidic shock is critical to elucidating how this bacterium survives the harsh environment of the human stomach. Understanding how H. pylori survives in the stomach can facilitate new treatment strategies and reveal how this pathogen has evolved to colonize its unique biological niche.
Using Laboratory-Confirmed Outcomes to Study Pediatric Influenza and Influenza Vaccine Epidemiology in Ontario
Keywords: epidemiology
influenza
pediatric
respiratory viruses
vaccine effectiveness

Annual epidemics of seasonal influenza continue to cause substantial morbidity in young children. Influenza is among several respiratory viruses that cause illness in children, in addition to a large burden on the healthcare system and society, but is the only one for which a vaccine is available. In this dissertation, I present three studies regarding the epidemiology of influenza in children under the age of five years using a novel approach of linking laboratory and health administrative data in Ontario. In a systematic review and meta-analysis of children presenting to healthcare who are tested for influenza, I found that 20% (95%CI 15%-25%) have laboratory-confirmed influenza, with variation across subgroups. I found that influenza represents a large overall burden of disease and a substantial proportion of healthcare encounters for respiratory illnesses. In a retrospective cohort study, I compared the characteristics, outcomes, and relative severity of illness of children who were hospitalized and tested for influenza A, influenza B, and respiratory syncytial virus (RSV) and were positive for only a single virus. I found that in-hospital outcomes and post-discharge healthcare utilization in children with no identified comorbidities were similar by virus type, but post-discharge healthcare utilization was higher for those with influenza in those with underlying comorbidities. I observed similar severity of illness, based on in-hospital outcomes, and cost of hospitalization between viruses. In a test-negative study, I estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations in children aged 6-59 months for the 2010-11 to 2013-14 seasons. I found that overall, VE was 51% (95%CI 38%-61%) for any vaccination, with variation by vaccination status (full vs. partial), season, age group, and subtype. These results indicate that large numbers of pediatric hospitalizations resulting from influenza infection could be prevented by promoting seasonal influenza vaccination each year. Overall, these results contribute to our understanding of pediatric respiratory viruses in Ontario, with each individual chapter adding to our knowledge regarding burden, severity, and prevention of influenza infection. These results can inform families, clinicians, public health practitioners, and policy makers in order to help reduce the impact of annual influenza infection in young children.
Contributions in Uncertainty Quantification Towards Reliability-based Rock Engineering Design
Keywords: Bayesian data analysis
Intact Rock Strength
Limit States Design
Reliability-based Design
Rock Engineering Design
Uncertainty Quantification

This thesis contributes to two distinct but related problems in contemporary rock engineering design which arise in the context of developing limit states design (LSD) protocols. In doing so, it identifies the discrepancies between geotechnical limit states design standards and customary rock engineering design procedures. These discrepancies are shown to be classified as (i) difficulties regarding definition of limit state functions stemming from model uncertainty, and (ii) parameter uncertainties stemming from lack of sufficient quantitative data. With regards to (i) above, this thesis demonstrates the existence of a significant component of neglected and unquantifiable model uncertainty in rock engineering, embodied in the form of various subjective-qualitative schemes (e.g. RMR, Q and GSI) commonly used in rock engineering. We suggest that the term “nebulous models” better describes the role of such schemes in engineering design, and discuss how their common application is a major obstacle to achieving rock engineering LSD, overcoming which requires community-wide efforts and a fundamental change in mindset. This thesis continues to discuss (ii) above in more detail. We introduce Bayesian data analysis (BDA) which allows logical augmentation of data with information from other sources (i.e. relevant historical data and expert knowledge) as a potential solution to the problem of limited data in rock engineering. Limiting our investigation to analysis of intact rock strength data, we develop Bayesian regression models that accommodate variability of strength data, and characterize the to-date neglected associated strength parameter uncertainties. We particularly address simultaneous analysis of tensile and compressive strength data. Furthermore, we propose a hierarchical Bayesian model for meta-analysis of rock strength data which results in shrinkage of uncertainty of estimated parameters. We further discuss how the results of this model may be used to augment future data. Also, this thesis develops a quantile regression model for obtaining strength curves that comply with LSD standard definitions of characteristic values. Finally, Bayesian regression analysis is used to reveal and characterize a neglected statistical property of strength of strongly anisotropic rock, namely, unequal variance with respect to loading direction. This thesis concludes with suggestions for the research required to further develop rock engineering LSD.
A population-based evaluation of long-term outcomes following major burn injury
Keywords: burns
epidemiology
health services research
outcomes

Introduction: Advances in critical care and the regionalization of burn care have resulted in a significant decrease in mortality after burn injury such that most burn-injured patients are expected to survive. This thesis aimed to evaluate and characterize long-term outcomes following major burn injury. Methods: Using linked health administrative data, we identified adults who sustained major burn injury during 2003-2014. First, we evaluated temporal changes in the incidence and in-hospital mortality of burn injury. We then estimated five-year risk-adjusted rates and principal causes of emergency department visits and readmissions. A self-matched longitudinal cohort study was performed to compare rates of mental illness-related healthcare utilization in the 3 years before and after burn. Finally, a matched cohort study was performed to estimate 5-year mortality after burn. Results: The incidence of burn injury remained stable over time, and significant reductions in the overall in-hospital mortality rate occurred; the odds of death in 2010-2013 were significantly lower than 2003-2006 (odds ratio (OR) 0.39, 95% CI 0.25-0.61). In the five years after discharge from the index burn admission, 70% of patients had >1 emergency department (ED) visit, and 30% had an unplanned readmission. The principal cause of healthcare utilization was unintentional injury, followed by mental illness and respiratory disease. Patients who received burn center care had significantly lower rates of ED visits (rate ratio 0.64, 95% CI 0.56-0.73) and readmissions (hazard ratio 0.77, 95% CI 0.65-0.92). Burn injury was not associated with a higher rate of mental health visits compared to the pre-injury period (RR 0.97, 95% CI 0.78-1.20), but was associated with a two-fold increase in self-harm (RR 1.95 (95% CI 1.15-3.33). Five-year mortality after burn injury was 11%, compared to 4% among matched controls. The hazard ratio was greatest during the first year after discharge (HR 4.15, 95% CI 3.17-5.42). Conclusions: Burn injury confers a physical and psychological impact up to five years after discharge, associated with high rates of healthcare utilization and increased late mortality compared to matched controls. Further development of consolidated and focused burn care, and improved mental healthcare, offer an opportunity to improve outcomes after burn injury.