VictorJuiz/thesis huggingface dataset:
The Function and Evolution of the Syncervical in Ceratopsian Dinosaurs with a Review of Cervical Fusion in Tetrapods
Keywords: functional morphology
cervical vertebrae

Mobility of the vertebral column is important for many ecological aspects of vertebrates, especially in the cervical series, which connects the head to the main body. Thus, fusion within the cervical series is hypothesized to have ecological and behavioural implications. Fused, anterior cervical vertebrae have evolved independently over 20 times in ecologically disparate amniotes, most commonly in pelagic, ricochetal, and fossorial taxa, suggesting an adaptive function for the ‘syncervical.’ Fusion may help increase out-force during head-lift digging or prevent anteroposteriorly shortened vertebrae from mechanically failing during locomotion, but no hypothesis for syncervical function has been tested. The syncervical of neoceratopsian dinosaurs is hypothesized to support large heads or aid in intraspecific combat. Tests of correlated character evolution within a ceratopsian phylogeny falsify these hypotheses, as the syncervical evolves before large heads and cranial weaponry. Alternative functional hypotheses may involve ancestral burrowing behaviour or unique feeding ecology in early neoceratopsians.
The Evaluation of Vertical Pole Configuration and Location on Assisting the Sit-to-stand Movement in Older Adults with Mobility Limitations
Keywords: Sit-to-stand
assistive device
grab bars

Grab-bars and transfer poles are common sit-to-stand aids for older adults with mobility limitations. This study investigates differences in kinematics and kinetics in the lower limbs across different transfer pole configurations and positions. Configurations tested are a single pole, two poles and a pole with a horizontal grab-bar at near and far positions. Three-dimensional biomechanics were used to calculate kinetics and kinematics of the lower extremities. Forces were also recorded from the pole. This study found horizontal pole forces were an effective replacement for trunk generated horizontal momentum. Reduced vertical pole forces were applied by participants using the `far' poles which resulted in increases in non-dominant hip moments when using the single and double pole configurations. Horizontal pole use introduced non-dominant directed lateral COM trajectory throughout the movement. This coincided with increased horizontal forces in the dominant foot to balance moments about COM in the transverse plane as a motor control strategy.
Towards Simplified Tools for Analysis of Reinforced Concrete Structures Subjected to Impact and Impulsive Loading: A Preliminary Investigation
Keywords: reinforced concrete
blast and impact
numerical modeling

The analysis of reinforced concrete structures under blast and impact loads is an area of research that has become increasingly relevant in recent years. Complex hydrocodes are typically used for impact analyses, although single-degree-of-freedom methods have also been developed. There are a number of disadvantages associated with both methods, and the Canadian Nuclear Safety Commission (CNSC) is looking for a tool that can be used in conjunction with hydrocodes to analyze hard and soft missile impacts, with target damage ranging from flexural cracking to perforation. The VecTor programs, a suite of nonlinear finite element programs developed at the University of Toronto for the analysis of reinforced concrete structures, can potentially be developed into such tools. The analytical work done in this study serves to investigate the current impact and impulse loading analysis capabilities in VecTor2 and VecTor3, and to identify areas where work should be focused in the future.
Evolution and Environmental Degradation of Superhydrophobic Aspen and Black Locust Leaf Surfaces
Keywords: Superhydrophobic surfaces
environmental degradation
evolution of superhydrophobic leaves
dual-scale roughness
wear and erosion of leaf surfaces
aspen and black locust leaf surfaces
evolution of leaf surfaces
superhydrophobic leaf surfaces
cuticular damage
micro and nano-scale roughness
biomimetics
nanomaterials
epicuticular wax morphologies
sensitivity to environmental stresses
micro-structured materials
nano-structured materials
nano-scale platelets
materials science
nanotechnology
materials engineering

The current study is focused on the characterization of four natural leaf species (quaking, bigtooth and columnar european aspen as well as black locust) possessing a unique dual-scale cuticle structure composed of micro- and nano-scale asperities, which are able to effectively resist wetting (superhydrophobic), characteristic of The Lotus Effect. Scanning Electron Microscopy (SEM) was used to track the growth and evolution of their distinctive nano-scale epicuticular wax (ECW) morphologies over one full growing season. In addition, the stability of their superhydrophobic property was tested in various environments. It was determined that the long-term stability of these surfaces is tentatively linked to various environmental stress factors. Specifically, a combination of high temperature and humidity caused the degradation of nano-scale asperities and loss of the superhydrophobic property. The dual-scale surface structure was found to provide a suitable template for the design of future superhydrophobic engineering materials.
Characterization of Hydrolytic Dehalogenases: Substrate Specificity and Isotope Fractionation
Keywords: Hydrolytic Dehalogenase
Bioremediation

The first project is focused on kinetic analysis of two enzymes: Rsc1362 (Ralstonia solanacearum GMI1000) and PA0810 (Pseudomonas aeruginosa PA01). Rsc1362 had a kcat of 504±66 min-1 and a KM of 0.06±0.02 mM, PA0810 had a kcat of 2.6±0.6 min-1 and a KM of 0.44±0.2 mM. A lack of environmental context for a chloroacetate dehalogenase was noted in Pseudomonas aeruginosa PA01. The second project focuses on kinetic and stable isotope fractionation of 1,2- dichloroethane by DhlA (Xanthobacter autotrophicus GJ10), and Jann2620 (Jannaschia CCS1). Although both enzymes had different kinetics (DhlA: KM = 4.8±0.6 mM and kcat = 133±8 min-1, Jann2620: KM = 25.9±2.3 mM and kcat = ~1.7 min-1), they fractionated similarly (ε values of -33.9‰ and -32.9‰ for DhlA and Jann2620, respectively). As calculated AKIE values were similar to the expected values of an abiotic reaction, it was determined that neither enzyme masks the intrinsic fractionation.
Improving Glucocorticoid Therapy in Chronic Lymphocytic Leukemia
Keywords: Glucocorticoids
Leukemia

Glucocorticoids (GCs) are commonly used in the clinic as a treatment for Chronic Lymphocytic Leukemia (CLL). The exact mechanism of GC action remains unclear and patients eventually develop resistance to this group of agents. Our findings show that GC-cytotoxicity in circulating CLL cells is caused by bioenergetic restriction resulting from the down-regulation of a key glycolytic enzyme, pyruvate kinase, muscle isozyme 2 (PKM2). Conversely, GCs were shown to promote fatty acid oxidation instead by up-regulating the expression of peroxisome proliferator activated receptor α (PPARα). These findings establish PPARα and fatty acid oxidation as novel mediators of GC resistance in CLL. Our findings also demonstrate that GCs enhance the cytotoxic effects of membrane-damaging agents such as ionophores and complement-mediated cytotoxicity. A clinically relevant agent known to intercalate in the cell membrane, Danazol was also found to have activity against CLL and can be combined safely with GCs for enhanced treatment efficacy.
Role of the STAS Domain of E coli Anion Transporter YchM
Keywords: SLC26
STAS domain
ACP
YchM

YchM is the sole E. coli member of the SLC26 superfamily of anion transporters, which are characterized by an N-terminal transport domain and a C-terminal cytosolic STAS (Sulphate Transporter and Anti-Sigma factor antagonist) domain. In a previous study, the STAS domain of YchM co-purified and crystallized with acyl carrier protein (ACP). In this study, analysis of the ACP-STAS interaction using isothermal titration calorimetry (ITC) showed that the 4’phosphopantetheine of ACP and R523 and R527 of the STAS are crucial for binding. The binding constant for the ACP-STAS interaction was found to be 0.7 +/- 0.1 μM. The potential role of YchM for pH regulation and fatty acid degradation studied in vivo indicated that a) YchM does not provide selective advantage for growth in alkaline pH and b) YchM was not essential for cell growth, even when fatty acids were the sole carbon source.
Validation and Mechanism Studies of Novel Therapeutic Compounds Modulating Angiogenesis
Keywords: angiogenesis
zebrafish
drug discovery
fenretinide
indirubin-3-monoxime
dihydromunduletone

Discovering novel compounds that stimulate or abrogate angiogenesis can lead to development of new therapeutic agents that may effectively treat diseases with pathological angiogenesis. The zebrafish model allows for a whole-organism approach to drug discovery. Advantages over other animal models include small embryo size, fecundity, rapid embryonic development, optical clarity and easy accessibility of the embryos. My goal is to validate the therapeutic efficacy and identify the molecular mechanisms of action of three compounds identified from our previous chemical genetic screens. Fenretinide promoted angiogenesis in zebrafish embryos but inhibited the angiogenesis-dependent process of fin regeneration. The pro-angiogenic effects of fenretinide appear secondary to the stimulation of somitogenesis. I3M potently inhibited angiogenesis and fin regeneration, and may act partially through the notch pathway. Lastly, I validated the anti-angiogenic effect of a novel compound DHM. Comprehensively, my studies support the utility of zebrafish as a versatile tool for anti-angiogenic drug discovery.
Self-referencing and Sensitivity Optimization in Photonic Crystal Slabs for Biosensing Applications
Keywords: photonic crystal
biosensing

Photonic crystal slabs (PCS) are explored in the context of optofluidic refractive index (RI) sensing for portable, label-free, biosensing applications. The accuracy of RI sensors is limited by noise signals that cause a change in RI that cannot be differentiated from the signal of interest. For this reason self-referencing schemes that provide rejection of common mode signals, and an inherent temperature stabilization approach, are explored. A novel referencing method that allows for frequency shifts to be read out in the transmission power spectrum is proposed and characterized. In terms of improving sensing metrics the relevant characteristics of various PCS architectures are explored numerically. In addition, a novel suspended \emph{air-substrate} device that offers greatly improved sensitivity is proposed and characterized. An experimental measurement near the theoretical detection limit for a PCS is demonstrated. In understanding measurement errors the crossed-polarization effect and its practical limitations are explored numerically.
The Role of Tim-3 Receptor in CD8+ T cells Cytotoxicity in Chronic HIV Infection
Keywords: HIV
Tim-3
Perforin
Cytotoxicity
Exhaustion

The Tim-3+ T cells in HIV infection are dysfunctional in proliferation or cytokine production. Here, we evaluated the effects of Tim-3 expression on the cytotoxicity of CD8+ T cells in HIV infection by examining 1) the ability of Tim-3+ CD8+ T cells to make perforin and 2) the direct ability of Tim-3+ CD8+ T cells to kill HIV infected CD4+ target cells. Tim-3+ CD8+ T cells maintained higher levels of perforin. However, these cells were defective in their ability to degranulate. Blocking the Tim-3 signalling pathway enhanced the cytotoxic capabilities of HIV specific CD8+ T cells by increasing: their degranulation capacity, their ability to release perforin, their ability to target activated granzyme B to HIV antigen expressing CD4+ T cells and their ability to suppress HIV infection of CD4+ T cells. Thus, the Tim-3 receptor can down-regulate the CD8+ T cell cytotoxicity through inhibition of degranulation and perforin/granzyme secretion.
Saccharomyces cerevisiae: A Platform for Structure-activity Relationship Analysis and High-throughput Candidate Prioritization
Keywords: chemogenomic
competitive growth
HIPHOP
yeast
platinum
saccharomyces cerevisiae
DNA damage
SAR
structure activity relationship
ACRAMTU
intercalation
mechanism of action
growth curve
biphasic
PCA
principal component analysis
hit prioritization

The budding yeast Saccharomyces cerevisiae has been an invaluable model organism in contributing to the current understanding of cellular biology, owing mainly to its highly tractable genetic system and the completion of its genome sequencing in 1996. Indeed, these bolstered the development of novel methods that have provided great insights into genetic and protein networks in human cells. With the large collection of datasets, S. cerevisiae also became an ideal platform for investigating the mechanism of action of novel compounds. The first part of my thesis uses a validated chemogenomic assay to investigate the mechanism of action of structurally related novel DNA-damaging agents, delineating valuable structure-activity relationship in the process. The second part describes the development of a method that uses drug-induced wild-type growth dynamic to characterize novel compounds, which, in combination with the chemogenomic assay, may complement existing high throughput screening experiments to improve the current drug development process.
Long-term Complications Associated with Implant-supported Complete Fixed Dental Prosthesis
Keywords: Dental Implants
Complications
Long-term Follow-up

Rehabilitation of edentulous patients with Implant-supported Complete Fixed Dental Prosthesis (ICFDP) is a well-documented treatment option. This dissertation assessed the relation between the rate of biological/mechanical complications and the type of metal framework alloy, length of cantilever extension. The results showed that long-term clinical outcomes of ICFDP were favorable. While 30% of patients experienced biological complications, 66.6% of the prostheses needed to be repaired during follow-up period. The risk of prosthesis failure and mechanical complications was significantly higher in silver-palladium frameworks as compared with palladium-silver or type IV gold alloys. The length of cantilever was not correlated with the amount of marginal bone loss. The rate of marginal bone loss around anterior implants was higher than that of posterior implants associated with cantilever segments. The treatment improved the patients’ quality of life and 96% of patients would undergo the same treatment again if required.
Bacterial Endophytes: Exploration of Methods and Analysis of Community Variation
Keywords: Bacteria
Bacterial endophytes
Endophytic community
Seasonal variation
Interspecies variation

Bacterial endophytes, bacteria residing within plants, play an important role in the growth and development of plants and their ability to thrive under adverse conditions. The endophytes of Acer negundo, Ulmus pumila and Ulmus parvifolia trees sampled from a hydrocarbon-contaminated site were analyzed for variation between seasons and plant species. Branches from the same trees over a span of 3 seasons were collected and analyzed via culture dependent and culture independent methods. Numerous culture independent approaches were tested, culminating in the development of a new method for the amplification of endophytic bacterial ribosomal DNA that excludes plastid DNA. Community analyses using this new method in combination with T-RFLP showed significant differences between the endophytic communities of different plants species and of the same species growing in different seasons. The proposed technique can be used for the future study of endophytic communities of plants.
Access to Neurosurgical Care for Traumatic Brain Injury in Ontario
Keywords: trauma
brain injury
access
neurosurgery
TBI
undertriage

Introduction: Trauma centers (TC) are the only institutions with resources to manage patients with severe traumatic brain injury (TBI). We chose to examine potential barriers to access to TC care for TBI patients. Methods: Administrative datasets were used to evaluate access to TC among patients with severe TBI. We examined triage practices of EMS in TBI. Finally, we analyzed surveys to capture the beliefs, perceptions and knowledge of ED physicians with respect to TBI. Results: 57% of patients in Ontario had any access to a TC following TBI. Of patients who had potential access to a TC from the scene of injury as defined by pre-hospital triage guidelines, 60% of patients were undertriaged. Challenges that ED physicians faced with managing TBI, included lack of beds at TC and difficulty attaining transport resources. Conclusion: Access to TC care for patients with TBI is impeded by patient and system level factors.
Adsorption of Single-ring Model Naphthenic Acid from Oil Sands Tailings Pond Water Using Petroleum Coke-derived Activated Carbon
Keywords: Naphthenic Acid
Petroleum Coke
Activated Carbon Adsorption
Tailings Ponds

Petroleum coke-derived activated carbons were prepared and used for the adsorptive removal of a single-ring naphthenic acid (NA) from synthetic oil sands tailings pond water (TPW). The overall adsorption process was found to be intra-particle diffusion-controlled. The Weber-Morris intra-particle diffusion rate constants decreased from 7.43 to 1.23 mg/g min0.5 after activated carbon was post-oxidized with oxygen, suggesting a hindering effect of oxygen surface groups. The Freundlich model fit of the equilibrium adsorption isotherms and the small negative ΔHo pointed to a physisorption-dominated process and the importance of specific surface area. It was estimated that about 2.7 g/L of basic CO2-activated carbon is needed to reduce NA concentration from 120 mg/L to 2.5 mg/L (~98% removal) in synthetic TPW. However, equilibrium adsorption capacity was found to vary significantly after oxygen or nitrogen groups were introduced onto the surface. Therefore, there is a potential for enhanced adsorption by chemical functionalization of carbon.
Hybrid Plasmonic Waveguides and Devices: Theory, Modeling and Experimental Demonstration
Keywords: plasmonic waveguide
polarizer
integrated optical circuit

This thesis prompt a theoretical analysis of the hybrid plasmonic waveguide (HPWG) and a TE-pass polarizer based on HPWG has been designed, fabricated and characterized. A combination of low propagation loss, high power density, and large confinement is useful for many applications. The analysis results in this thesis show that the HPWG offers a better compromise between loss and confinement as compared to pure plasmonic waveguides. Another interesting property of the HPWG is its polarization diversity. In the HPWG the transverse electric and the transverse magnetic modes reside in different layers. We have designed a very compact hybrid TE-pass polarizer using this property. The polarizer was fabricated and characterized. The device shows low insertion loss for the TE mode with a high extinction ratio at telecommunication wavelength range for a 30 µm long HPWG section. Its performance compares favorably against previously reported silicon based integrated optic TE-pass polarizers.
Impact of Pretreatment Methods on Enzymatic Hydrolysis of Softwood
Keywords: Biomass
Pretreatment
Enzymatic Hydrolysis
Autohydrolysis
Steam Explosion
Multistage
Lignocellulose
Softwood
Bioethanol

Bioethanol is an appealing alternative to petroleum-based liquid fuel due to drivers such as environmental regulations and government mandates. Second generation lignocellulosic feedstocks are abundant, but their resistance to hydrolysis continues to be problematic. Different pretreatments have been proposed to increase cellulose reactivity. Softwood pine autohydrolyzed at different severities was subjected to further treatment to increase fibre reactivity. Liquid hot water is most effective at removing barriers, with the highest increase in sugar yield after enzymatic hydrolysis. Alkaline (NaOH) is found to be the worst option compared to dilute acid and organosolv. In addition, higher chemical concentrations and longer treatment times do not guarantee higher enzymatic hydrolysis yield. Process modifications such as fiber washing and multistage enzymatic hydrolysis are observed to be effective at increasing yield. However, more research is required to bring the enzymatic hydrolysis yield to a level where commercialization is feasible.
Characterization of an Electrospray with Co-flowing Gas
Keywords: Electrospray
Characterization
Co-Flowing Gas
Nebulizer
Droplet Size
Cone Jet
Mass Spectrometry
Spray

In mass spectrometry an electrospray is commonly used as an ion source. At high sample flow rates a sheath co-flow of gas around the electrospray emitter is employed. The co-flow of gas reduces contamination and increases signal sensitivity in the mass spectrometer’s results. This work characterizes the operation of an electrospray with co-flowing air for various operating conditions. It is found that a co-flowing air has a negligible effect on droplet size for the spindle and cone jet modes while it only reduces the droplet size marginally in the unstable mode. In the high flow rate unstable mode, the addition of air seems to have no real effect on droplet size. In summary, the electrospray with co-flowing air produces a denser and more focused spray with similar droplet size and distribution than that of the un-nebulized spray. This explains why using co-flowing air in mass spectrometry applications improves the signal quality, since it allows for the focusing of droplets produced into the inlet and also aids in the breakup of larger droplets.
Investigating the Hippo Signaling Pathway using High-throughput Protein-protein Interaction LUMIER Screens
Keywords: Biochemistry
Molecular Biology

The Hippo pathway plays a key role in controlling organ growth and size. In mammals, core pathway components include the Lats1/2 and Mst1/2 kinases, which phosphorylate the transcriptional regulators, Taz and Yap. To identify novel upstream pathway regulators high throughput protein-protein interaction screens, called LUMIER (LUminescence-based Mammalian IntERactome) were performed together with a functional screen using a luciferase reporter that examines Hippo pathway responses. The screens revealed 1103 protein-protein interactions and 227 transcriptional regulators, which were particularly enriched in cytoskeletal regulators. A subset of these hits including BTK, Dvl1, Dvl2, Dvl3, Ing2, Magi2, Mark4 and Trip6 were validated by manual LUMIER assays and co-immunoprecipitation (Co-IP). Of particular interest was the microtubule dynamics regulatory protein MARK4. Loss of Mark4 prevents Taz activity demonstrating its role as a potential negative regulator of the Hippo pathway. Further studies could help decipher mechanisms of how Mark4 and the other cytoskeletal hits act to modulate the Hippo pathway.
Differential Effects of NMDA Receptor Antagonism on Spine Density
Keywords: NMDA receptor antagonism
Ketamine
MK-801
Spine density
Depression

Recent studies have demonstrated that an acute, low dose of ketamine, a non-competitive NMDA receptor antagonist, provides rapid and sustained antidepressant effects in patients with major depressive disorder. Studies in rodents have shown that the antidepressant properties of ketamine are due to an increase in dendritic spine density in the cortex. Our goal was to determine whether these effects are specific to ketamine and whether they are dependent on dose, drug regimen and brain region. We observed that the effects of ketamine on spine density were dependent on dose and drug regimen and were also brain region specific. In addition, MK-801, another NMDA receptor antagonist, did not demonstrate the same effects on spine density as ketamine. Furthermore, genetic NMDA receptor hypofunction significantly reduced spine density. Our studies demonstrate that while acute ketamine treatment leads to an increase in cortical spine density, chronic administration has opposite and potentially detrimental effects.