VictorJuiz/thesis huggingface dataset:
Detection and Occurrence of Microplastics through Municipal and Pilot-scale Drinking Water Treatment Plants

Concern regarding microplastic contamination in the environment by water providers and consumers has led to the investigation of microplastics in drinking water. Here, the development of a new method is described for microplastic analysis in drinking water samples, minimizing contamination and applying relevant QA/QC guidelines. The described method achieved an overall recovery of >80% for microplastics of various sizes, shapes, and composition, in drinking water matrices. Additionally, a full-scale conventional drinking water treatment plant employing coagulation, flocculation, filtration, and chlorination was sampled for microplastics, alongside a pilot-scale plant with eight parallel filters, receiving different treatment. Full-scale treatment removed 52% of microplastics from raw (42 ± 18 particles/L) to tap water (20 ± 8 particles/L). Ozonation, media type, biological contact, and flow rate through the filters contributed no additional removal. Coagulation, flocculation, and sedimentation accounted for 70% of particle removal, the highest removal of unit processes examined.

Keywords: Biofiltration
Drinking Water Treatment
Microplastic removal
Microplastics
Particle enumeration
QA/QC
Advisor: Andrews, Robert C
Autonomous Mobile Robot Navigation in 3D Rough Terrain using Deep Reinforcement Learning

Autonomous 3D rough terrain navigation requires a mobile robot to maneuver cluttered environments that have abrupt changes in terrain elevation and surface normal. Thus a navigation framework is required to determine the traversability of robot surrounding terrain using onboard sensory inputs, and overcome disturbances from 3D terrain interactions and sensor noises. This thesis presents a rough terrain navigation framework developed in simulation using deep reinforcement learning and a novel sim-to-real pipeline to overcome the gap between simulation and the real world. The pipeline was incorporated into a mobile robot architecture and the real-world experiments showed that the robot was able to successfully navigate from any arbitrary starting location to arbitrary goal location in the real-world 3D terrain.

Keywords: Deep Reinforcement Learning
Mobile Robotics
Rough Terrain Navigatin
Advisor: Nejat, Goldie
Low-power Edge-combining Ring-oscillator-based RF Transmitters for Flexible-electrode Neural Microimplants

The vision of distributed microimplants for neuromodulation at the spatial scale of a single neuron calls for closed-loop wireless transmitters (TX) with ultra-small area and power. Gold-standard LC-oscillators are power-efficient but their dimensions scale down poorly at sub-GHz frequencies preferable for low tissue attenuation. Ring-oscillators (ROs) are compact but are too power-hungry for microimplant power budgets. This thesis proposes the use of frequency-multiplying edge-combining (EC) techniques for synthesizing a high-frequency RF TX carrier from a slower and lower-power RO core. It presents two alternative methods of voltage-mode and current-mode EC by exploiting inherent properties of ROs with minimal or no circuit overhead. The two techniques are validated in the design of two ISM-915MHz direct modulation transmitters fabricated in a 65nm CMOS process. Both designs achieve sub-50x50μm dimensions and sub-100μW power consumption at 20Mbps output data rate while meeting the sub-50nS wakeup requirement for event-based wireless communication in neural microimplants.

Keywords: Biomedical
Edge-combining
Integrated Circuits
Low Power
Neural Implants
RF Transmitters
Advisor: Genov, Roman
Dreissenid Mussel Control in Drinking Water Treatment Plants: Temperature Effects and a Copper-based Alternative

The validity of a temperature-based threshold for starting prechlorination for dreissenid mussel control in water treatment plants was evaluated by monitoring larval settlement onto surfaces for two years at three utilities in Lake Ontario. Temperature was a poor predictor of mussel settlement, but settlement was consistently observed between July and November. Therefore, a calendar-based approach for prechlorination was proposed. Chlorine is effective against dreissenids, but it enhances the formation of disinfection by-products. A copper-based product was analyzed as an alternative to chlorine. Doses as low as 30 µg/L of copper were observed to produce increased larval mortality compared to controls. The impacts of copper on coagulation/flocculation and dual media, GAC, and biologically active filtration were studied. Copper was removed to different extents by the different treatment processes. No significant adverse impacts on the performance of these processes were noted. However, studies of longer duration are required to support these findings.

Keywords: Conventional Water Treatment Processes
Copper-Based Product
Dreissenid Mussels
Drinking Water Treatment
Prechlorination
Advisor: Hofmann, Ronald
The Role of Allosteric Scaffolds and Protein Dynamics in Enzyme Function – Lessons Learned by NMR

Most proteins undergo significant cooperative processes over timescales spanning microseconds to many milliseconds. These dynamic processes allow the protein to span the entire reaction coordinate and accomplish its function. Thus, protein function is generally not achieved by a single conformer but rather through a functional ensemble of conformers. Here, we focus on a homodimeric enzyme, fluoroacetate dehalogenase (FAcD) which cleaves the CF bond - one of the strongest covalent bonds in nature - generating fluoride, water, and glycolate from fluoroacetate. The enzyme functions through half-of-sites reactivity where only one protomer is catalytically active. The empty protomer releases ~30 bound water molecules during the catalytic step, thereby entropically favouring the forward reaction. This thesis focuses on using NMR, crystallography and computational studies to study protein dynamics. Specifically, evaluating substrate and product-based regulation, asymmetry in a homodimeric enzyme, disruptions to the allosteric network, and inhibited dynamics due to induced stiffness.

Advisor: Prosser, Robert Scott
Design and Evaluation of Orthopedic Alignment Tools for Guidewire and Screw Insertion

The Femoral Antegrade Starting Tool (FAST) was invented to facilitate guidewire alignment in femoral intramedullary nailing procedures. Previous cadaver studies demonstrated FAST’s potential to reduce surgical time and radiation exposure. This thesis continued the development of FAST through a first in human trial and expanded the guidewire insertion technology to be applicable to pelvic reconstruction procedures. The FAST design was enhanced for usability, manufacturability, assembly, sterilization and cleaning. A clinical pilot study to evaluate the tool’s safety and surgical workflow was planned and successfully executed (n=10). Expanding the technology to pelvic reconstruction included consultations with surgeons, substantial design changes, prototyping and simple usability studies. This resulted in the creation of two proof of concept prototypes. Initial surgeon feedback supports the potential of FAST and the pelvic guidewire/screw positioning tool. Further improvements to the FAST and pelvic tool workflows and designs are suggested towards ultimately bringing these technologies into clinical practice.

Keywords: Clinical Study
Design
Orthopedics
Product Development
Surgical Tools
Advisor: Whyne, Cari
The Role of Endothelial-Specific Intraflagellar Transport Protein 88 in Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) has been associated with cardiotoxicity resulting in heart failure. Previous studies focused on cardiomyocytes as therapeutic targets. However, there has been a shift of focus toward endothelial cells (ECs) due to its importance in cardioprotective processes. Recently, a role for EC primary cilia as central structures that govern EC function through downstream signaling upon blood flow stimulation was identified. Intraflagellar transport protein 88 (IFT88) is critical for ciliary formation. In our study, mice with EC-specific loss of IFT88 expression (EC-IFT88-/-) were utilized to investigate the role of EC primary cilia in DOX-induced cardiotoxicity. We observed greater DOX-induced mortality and reduced cardiac function in EC-IFT88-/- mice compared to wild-type (WT) littermates. Furthermore, weakened statistical power may have contributed to unobservable significant differences in CM vacuolization and cardiac fibrosis of DOX-treated EC-IFT88-/- and WT littermates. Thus, EC primary cilia may be involved with processes that are protective of DOX-induced cardiotoxicity.

Keywords: Cardiovascular Sciences
Doxorubicin
Heart Failure
Mouse Study
Primary Cilia
Advisor: Verma, Subodh
Total Folate and Synthetic Folic Acid Content in the Food Supply and Its Influence on Absorption Across the Colon

To reduce the risk of neural tube defect-affected pregnancies in Canada, folic acid fortification of foods is mandated, and women planning a pregnancy are advised to consume a folic acid-containing supplement. This research aims to determine the amount of folic acid in fortified foods and understand the impact of folic acid on folate absorption in the colon. In study one, analysis of fortified foods by microbial analysis and mass spectroscopy showed 65% higher folate values than in the Canadian Nutrient File. In study two, an on-going randomized clinical trial, we seek to investigate the influence of folic acid on folate absorption in the colon. Data herein verify the feasibility of the protocol and that the feeding and supplement intervention produced two distinct groups in terms of blood folate status. This work will facilitate an improved understanding of available sources of folate to inform future folate supplementation and fortification recommendations.

Keywords: Absorption
Folate
Folate Status
Folic Acid
Food Fortification
Advisor: O'Connor, Deborah L
Kim, Young-In
Degradation of Phospholamban Disease Mutants in Neonatal Mouse Ventricular Cardiomyocytes

Dilated cardiomyopathy (DCM) affects 1 in 500 individuals worldwide. Half of these cases have a genetic basis and Phospholamban is often implicated. PLN is the principal inhibitor of sarco(endo)plasmic reticulum Ca2+ ATPase and thus instrumental in cardiac Ca2+-cycling. Mutations in PLN, Rdel14 and L39Stop, result in DCM and present with distinct cellular protein localizations possibly attributed to aberrations in degradation. I thus aimed to determine the mechanisms underlying the degradation of Rdel14, and L39Stop. I hypothesized that Rdel14 and L39Stop are subjected to an increased degree of degradation by autophagy. Immunoprecipitations and immunofluorescence in HEK293T cells and neonatal cardiomyocytes indicate that Rdel14 is ubiquitinated, and interacts with p62, but does not colocalize with autophagosomes, suggesting defective trafficking. Similar experiments on L39Stop demonstrated a complete absence of expression. This work contributes to the expanding PLN interactome which will provide insight to cardiomyopathies that have a basis in defective Ca2+ cycling.

Keywords: Autophagy
Calcium Cycling
Heart Failure
Phospholamban
Advisor: Gramolini, Anthony O
An Exploration of How Male Adolescents who had Childhood Cancer Make Sense of Infertility as a Long-term Effect of Cancer Treatments

Clinical practice guidelines recommend that healthcare professionals (HCPs) discuss fertility preservation (FP) with cancer patients, however studies show that many HCPs do not initiate these discussions with male adolescents. Research examining male adolescents’ perceptions of potential infertility is also limited. Using Frank’s three narrative typologies (restitution, quest, and chaos narratives) as a conceptual framework through which to examine a collection of interviews with 14-18 year old males, this study examines how male adolescent childhood cancer survivors make sense of infertility as a long-term effect of cancer treatments and explores how their experiences of cancer shape their identities. Findings: i) all three narrative types were evident in the interviews with an emphasis on the restitution and quest narratives; ii) the narratives highlighted the important role of family in the adolescents’ understanding and experience of infertility; and iii) the narratives shed light on the importance of biological parenthood to the participants.

Keywords: Adolescent
Cancer
Fertility preservation
Narrative methods
Quality of Life
Advisor: Gibson, Jennifer L
Degradative Activities of Human Neutrophils toward the Tooth, Restoration and Restoration-tooth Interface

Human neutrophils constantly enter the mouth and release catabolic factors that are hypothesized to biodegrade the restoration, tooth and the restoration-tooth interface. Blood neutrophils were shown to have esterase-like and protease, matrix-metalloproteinase-like activities measured with colorimetric and fluorometric assays. Resin monomers, resin composite, resin adhesives, and tooth dentin were degraded by neutrophils in a material dependant manner, as measured by quantifying degradation by-products using ultra-performance-liquid-chromatography and imaged with scanning electron microscopy. Neutrophils also affected fracture toughness and fracture mode of restoration-tooth specimens compared to incubation with media alone. The above suggest a potential role of neutrophils in the development of primary and secondary caries, a significant health, and economic burden with more than 16 million restorations placed in Canada at a cost of $3B, mostly due to replacement of failed restorations. The development of materials and techniques to reduce degradation of restorations, restoration’s margins and tooth could enhance restoration longevity.

Keywords: Biodegradation
Dental caries
Dental restoration failure
Host-biomaterial interactions
Innate immune system
Advisor: Finer, Yoav
Glogauer, Michael
Investigating the Regulation and Function of DARC in Primary Human Microvascular Endothelial Cells

The Duffy antigen receptor for chemokines (DARC) is a blood group antigen expressed on erythrocytes and endothelial cells (ECs) of the post-capillary venules. Regulation and function of endothelial-specific DARC remains unclear due to the lack of literature attributed to its loss of expression in culture within 2 days of isolation from tissue. We hypothesized that DARC expression is regulated by tissue microenvironment. Using primary human pulmonary microvascular ECs, we showed that 24 hour incubation with human whole blood leads to endothelial-specific DARC expression. Removal of blood following induction resulted in loss of DARC protein and mRNA within 24 hours; protein loss was found to be independent of the proteasome and matrix metalloproteinases. Together, these findings demonstrate that endothelial DARC expression is regulated by mediators from the microenvironment, and its regulation is likely to have implications for our understanding of how cultured cells maintain or lose their in-situ tissue phenotype.

Keywords: ACKR1
DARC
Endothelial Cells
Microvasculature
Advisor: Lee, Warren L
Defining Conditions for Guided Mineralization of Amelogenin Ribbons by Amelotin

Living organisms build inorganic materials, biominerals, by a process called biomineralization. A key step in the formation of biological structures, including biominerals, is the assembly of extracellular matrices, which act as scaffolds to aid in the formation of the final product. Two proteins that play key roles in enamel formation are Amelogenin (AMEL) and Amelotin (AMTN). AMEL has been proposed to act primarily as a biological scaffold, while AMTN acts as promotor of crystallization. In this project, we have investigated the in vitro self-assembly and co-assembly of these proteins in a solution containing calcium and phosphate ions. We have shown that AMEL self-assembled structures, such as nanoribbons, serve as templates for mineralization while self-assembled AMTN promotes mineralization. The self-assembly of AMEL and AMTN were characterized by atomic force microscopy and transmission electron microscopy under varying physicochemical conditions. This project has furthered our knowledge on the process of biomineralization.

Keywords: Amelogenin
Amelotin
Biomineralization
Enamel
Advisor: Carneiro, Karina
Ganss, Bernhard
Non-nutritive Sweetened Beverages and Cardiometabolic Risk

Whether non-nutritive sweetened beverages (NSBs) improve cardiometabolic risk factors similar to water in their intended substitution for sugar sweetened beverages (SSBs) is unclear. To assess the effect of 3 prespecified substitutions (NSBs for SSBs, NSBs for water and water for SSBs) on body weight and cardiometabolic risk factors, we undertook a systematic review and network meta-analysis. Fourteen trials (n=1530) predominantly in people with overweight/obesity at risk for or with diabetes were identified. The substitution of NSBs for SSBs improved body weight, BMI, body fat, triglycerides and intrahepatocellular lipids supporting the use of NSBs, as a viable alternative to water, for SSBs. Due to imprecision in the estimate and concerns that NSBs adversely affect glucose tolerance through compositional gut microbiome changes, we provided a rationale, design and baseline characteristics report for the STOP Sugars NOW trial to determine the effect of our 3 prespecified substitutions on gut microbiome and glucose tolerance.

Keywords: cardiometabolic risk
low-calorie sweetener
network meta-analysis
non-nutritive sweetener
sugar-sweetened beverage
systematic review
Advisor: Sievenpiper, John L
The Effects of Tobacco Smoke and Nicotine on Lung CYP2A Expression in Humans and Monkey Model

Smoking can decrease CYP2A6-mediated nicotine clearance through downregulation of hepatic CYP2A6. It is unknown if nicotine has similar effects on CYP2A in extrahepatic tissues, particularly lung. We investigated the association between smoking and lung CYP2A mRNA levels and assessed whether chronic nicotine treatment alters lung CYP2A proteins. Lung CYP2A13, CYP2A6, and CYP2A7 mRNA levels were compared between smokers and nonsmokers. Lung CYP2A protein levels were compared between nicotine-treated and vehicle-treated monkeys, with and without ethanol self-administration. Smoking status was associated with lower levels of human lung CYP2A13, CYP2A6, and CYP2A7 mRNA, and nicotine treatment lowered monkey lung CYP2A protein. There were no effects of ethanol or drug interactions on lung CYP2A protein. Smoking and/or nicotine can decrease lung CYP2A expression, similar to their effect on hepatic CYP2A6. This regulation may impact the localized metabolism of CYP2A substrates in the lung such as nicotine-derived procarcinogens.

Advisor: Tyndale, Rachel F
Comparing the Effects of α5GABAA Receptor Negative Allosteric Modulators on Inhibitory Currents in Hippocampal Neurons

Overactivity of α5 subunit-containing GABAA (α5GABAA) receptors contributes to cognitive deficits in many neurological disorders. Negative allosteric modulators that preferentially inhibit α5GABAA receptors (α5-NAMs) have been developed to treat such deficits. α5-NAMs have been primarily studied using recombinant GABAA receptors expressed in non-neuronal cells. Surprisingly, although the native neuronal environment influences GABAA receptor pharmacology, no study has directly compared α5-NAM effects on GABAA receptors expressed in primary neurons. This comparison would aid in the development and selection of more effective compounds for clinical trials. Thus, the current study was undertaken to compare the effects of five α5-NAMs on the function of GABAA receptors in cultured mouse hippocampal neurons, using whole-cell voltage-clamp recordings. While α5-NAMs similarly inhibited GABAA receptor-mediated currents; the most efficacious concentrations varied 100-fold. Given that maximal efficacy is similar among α5-NAMs, factors such as potency, selectivity, and toxicity should be emphasized in the development and selection of α5-NAMs for clinical trials.

Advisor: Orser, Beverley
Numerical Experiments on the Role of Adhesion in Shotcrete Behaviour

Shotcrete has been widely used as surface support for underground excavations. However, the complex interactions between the shotcrete and rock is not well understood. This thesis aims to further develop the understanding of the mechanical behaviour of shotcrete with a particular focus on adhesion. A critical review of laboratory tests, analytical studies, and numerical investigations on shotcrete behaviours has led to the design of a series of numerical experiments. A 3D Discrete Element numerical model was used to capture the adhesion failure mechanism of a shotcrete liner. This was calibrated to the results from well documented laboratory investigations. Structural liner element was successfully implemented to simulate the behaviour of shotcrete liners. The thesis describes how input material properties and liner element geometry govern the overall mechanical behaviour of structural liner. A series of parametric tests demonstrated the impact of geometry, age, thickness, and adhesion on the performance of shotcrete liner.

Keywords: Adhesion
Adhesion failure
DEM
Numerical modelling
Shotcrete
Structural liner element
Advisor: Hadjigeorgiou, John
Karampinos, Efstratios
Pressure Drop of a Shear-thinning Fluid in a Converging Channel

The pressure drop of four concentrated aqueous viscoelastic solutions flowing through a long hyperbolic converging channel was measured. The channel was designed by a previous student to maximize extensional stresses, and to avoid an upstream vortex, which caused increased pressure drops in others’ work. Pressure drops with elastic, constant-viscosity dilute solutions equalled their inelastic equivalents. In the present work, concentrated polyethlyene oxide solutions were tested in the same channel. Rheological characterization showed that they followed the power law model. At low flow rates, theoretical inelastic predictions and experimental values agreed. At high flow rates, elastic effects caused an increased pressure drop, compared to predictions. The similarity with other works in the literature suggests that the increase in the pressure drops was due to changes in the flow field.

Keywords: Converging Channel
Polymer Solution
Pressure Drop
Shear-Thinning
Advisor: James, David
The Role of Lipid Transfer Proteins in Autophagy

Macroautophagy (hereafter autophagy) is a degradative cellular pathway that helps to maintain cellular homeostasis by delivering cargo to lysosomes. This pathway involves the generation of an autophagosome that engulfs cargo for degradation. The origin of the autophagosome membrane is still under debate but it is clear that multiple organelles are involved and membrane contact sites are important for their formation. Here, I examined the role of lipid transfer proteins (LTPs) in autophagy. I found that the LTPs OSBPL7 and OSBPL11 and their binding partner, VAPA, are required for autophagy of S.Typhimurium and for the clearance of ubiquitinated protein aggregates. OSBPL7 and OSBPL11 were found to be required for the lipidation of LC3-I to LC3-II during autophagy. I demonstrated that OSBPL11, but not OSBPL7, is involved in the localization of phosphatidylinositol 4-phosphate to autophagosomes containing S.Typhimurium. These results suggest that OSBPL7 and OSBPL11 play a key role in autophagosome formation.

Keywords: Autophagy
Lipid Transfer Proteins
Advisor: Brumell, John H