VictorJuiz/thesis huggingface dataset:
Desorption of Organotin and Organophosphorus Compounds from Virgin Polyvinyl Chloride (PVC) Microplastics in Freshwater

Microplastics (MPs) are ubiquitous in the environment. Health concerns exist regarding chemicals that have been added during plastic production and may desorb from MPs into water. Previous studies have examined desorption of chemical additives from MPs into marine environments, however only limited studies consider freshwaters that also represent sources of drinking water. This thesis examined the desorption of two groups of chemical additives, organotin (OTCs) and organophosphorus compounds (OPs) from virgin polyvinyl chloride (PVC) in artificial freshwater (AFW). Higher desorption was observed when considering smaller size (45 - 125 µm) PVC particles compared to larger (300 - 500 µm) particles. Water quality factors including pH and the presence of chlorine or chloramines were observed to impact OTC desorption. This thesis provides new information regarding the desorption of chemical additives such that potential risks may be better understood when considering freshwater sources of drinking water.

Keywords: Chemical additives
Microplastics
Organotin
PVC
Advisor: Andrews, Robert RCA
Peng, Hui HP
Characterizing the Roles of RNF168 and RNF169 in Mammary Tumourigenesis

Dysregulated DNA damage response (DDR) often leads to genomic instability, carcinogenesis, and other diseases. Thus, elucidating molecular mechanisms of DNA repair has tremendous therapeutic implications. RNF168 is a RING E3 ligase with essential roles in the repair of DNA double-strand breaks (DSBs). Its paralog RNF169 has been proposed to impede recruitment of DDR effectors downstream of RNF168. In the present study, novel roles of RNF168 and RNF169 in tumourigenesis were identified. Mice with germline mutations for Rnf169 are predisposed to developing mammary tumours, whereas those with an additional loss of Rnf168 are protected. This protection occurs at the cost of compromised DSB repair and ability to recruit DDR effector proteins to DSBs. In addition, this study also implicates RNF168 and RNF169 in regulating mammary side branching. These findings identify novel functional interactions of RNF168 and RNF169 and suggest potential therapeutic implications by means of modulating DSB repair pathways.

Keywords: breast cancer
breast tumour
DNA damage
Double-strand break
RNF168
RNF169
Advisor: Hakem, Razq
Structural Insight into a Member of the Schizorhodopsin Family

Microbial rhodopsins are the best-studied photosensitive proteins that are involved in ion transport in cells. Upon light activation, these rhodopsins can act as inward Cl- pumps, outward H+ pumps or ion channels to maintain a membrane potential and have more functions such as photosensors and light-switchable enzymes. A recent study illustrated the discovery of a new microbial rhodopsin family – schizorhodopsins. A member of this new family, Antarctic Rhodopsin (AntR), is found in microbial life located in Antarctic lakes. AntR has been well characterized biophysically, however, the molecular structure of AntR remained elusive. Through X-ray crystallography, I determined the structure of AntR under acidic and basic conditions. The structure showed the typical seven transmembrane helix bundle and revealed a subsequent cytoplasmic helix located at the C-terminus. This cytoplasmic helix is unique in microbial rhodopsins and its deletion resulted in a slower photocycle to pump protons but increased thermal stability.

Keywords: Crystallization
EPR Spectroscopy
Membrane protein
Microbial rhodopsin
Structural biology
X-ray crystallography
Advisor: Ernst, Oliver P
The Role of Paramedics in Integrated Care

Health systems look to improve by enacting principles of ‘integrated care,’ but lack guidance on being responsive to local needs. This qualitative study examined the evolving role of paramedics in integrated care, finding that paramedics fill localized gaps in health and social services and serve as flexible, adaptive capacity in health systems. They perform unscheduled response functions and support prevention and primary care, targeting both broad, low-needs populations and more complex, high-needs populations. The findings support that integrated care systems can be enhanced by community-based services accessed through a single-point-of-entry, delivered by a generalist, flexible health workforce that is mobile in the community. This means fostering local organizational networks, allowing local control and experimentation, balancing standardization with flexibility and assessing value at a system level. Further work is needed on governance approaches to enable this, and clarifying the role of paramedics in the skill mix of integrated care teams.

Keywords: complex systems
governance
health policy
integrated care
paramedic
Advisor: Kuluski, Kerry
Pinto, Andrew D
Characterizing the Window of Vulnerability in a Mouse Model of Mild Traumatic Brain Injury

Following one mild traumatic brain injury (mTBI), there is a window of vulnerability during which subsequent mTBIs can cause exacerbated impairments. I characterized this window in mice by giving them one or two mTBIs separated by various intervals and measuring their resulting behavioural impairment using the Y-maze, visual cliff, and novel object recognition tests as well as their white matter pathology by silver staining. The window of vulnerability following our lab’s mTBI model was over 2 weeks when defined by silver staining but was not detectable when defined by behavioural testing. I also found that sex and impact severity differentially affect post-mTBI vulnerability in different white matter regions. This work highlights the value of including white matter damage, sex, and replicable mTBI models for the study of post-mTBI vulnerability. As well, this work establishes important groundwork for the future investigation of mechanisms, biomarkers, and therapies for post-mTBI vulnerability.

Keywords: axons
concussion
mild traumatic brain injury
mouse model
white matter
Advisor: Wheeler, Anne L
Towards an Injectable Hydrogel for the Delivery of Thermostable Chondroitinase ABC

Chondroitinase-ABC (ChABC) is a bacterial enzyme that has immense potential as a therapy for central nervous system injuries due to its ability to degrade the chondroitin sulfate proteoglycans of the glial scar; however, its clinical translation has been thwarted by its thermal instability and lack of an optimal delivery strategy. In this thesis, we compared two delivery vehicles for the affinity-release of thermostabilized ChABC expressed with a Src homology 3 domain (ChABC-37-SH3): a tetrazine-norbornene-crosslinked carboxymethylcellulose hydrogel (CMC), and a biodegradable, oxime-crosslinked dextrin-gelatin-based hydrogel (Dexime). Cytocompatibility of both gels was demonstrated using neural progenitor cells and microglia in vitro. Rigorous mechanical characterization revealed their tuneability with crosslink density. Notably, sustained release of bioactive ChABC-37-SH3 was achieved from CMC over 7 days. In contrast, limited release was observed from Dexime due to the potential adsorption of ChABC-37-SH3 to gelatin. Based on these studies, CMC was the preferred hydrogel for affinity-release of ChABC-37-SH3.

Keywords: Chondroitinase ABC
Controlled Release
Delivery
Hydrogel
Protein
Stroke
Advisor: Shoichet, Molly
Investigating the Role of the SUMO System in PAX5- ETV6-driven Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer, diagnosed in ~1140 children every year in Canada. Despite a high 5-year survival rate, it remains one of the leading causes of cancer morbidity and mortality in children. Predisposing factors of ALL include several chromosomal translocations that give rise to fusion proteins. Among them is PAX5-ETV6, a gene fusion present in ~1% of pediatric ALL cases. Very little is known about the PAX5-ETV6 protein interactome. Using proximity-dependent biotinylation, I found a prominent association between PAX5-ETV6 and components of the SUMO system, which plays important roles in heterochromatin formation and maintenance. A better understanding of this interaction could help shed light on the initiation mechanism for this disease and importantly - could be targeted therapeutically. So, I investigated the role of the SUMO system in PAX5-ETV6 leukemogenesis and examined the possible therapeutic effects of SUMO inhibitors on these types of cancers.

Keywords: Acute Lymphoblastic Leukemia
Leukemia
Proteomics
SUMO
ZMYM2
Advisor: Raught, Brian
A Comparative Study of Regular- and High-fidelity Solvers for the Prediction of Aortic Hemodynamics

Computational Fluid Dynamics (CFD) simulations of cardiovascular systems are currently very time consuming. Simulation results significantly depend on the specific algorithms used and inappropriate choices of their settings may compromise accuracy. There is a clear need to understand the impact of algorithms and spatial/temporal resolutions on the accuracy of hemodynamics results. More efficient algorithms for cardiovascular flows in thoracic aorta are needed to allow incorporation of CFD simulations into the clinical decision cycle. In this thesis, we conducted a comparative study between regular-fidelity and high-fidelity CFD algorithms, in terms of performance and accuracy of predicted hemodynamic indices. The high-fidelity solver showed a superiority in detecting high-frequency flow patterns and, on par of accuracy, the high-fidelity solver was 150 times faster compared to the regular-fidelity solver. This thesis can also serve as a guideline to the selection of temporal and spatial resolutions to achieve accurate hemodynamic results for patient-specific aortic flow simulations.

Keywords: Aorta Simulation
Aortic Hemodynamics
Computational Fluid Dynamics
Finite Element Methods
High-fidelity Solver
Advisor: Triverio, Piero
Jimenez Juan, Laura
Optical Measurement of Highly Reflective Surfaces

Measuring objects that have highly reflective surfaces with structured light (SL) is challenging. In traditional high dynamic range (HDR)-based technique, cumbersome exposure selection strategies are employed. This thesis proposes two novel SL-based methods to measure parts with highly reflective surfaces. First, an image enhancement-based method with only single exposure is developed. A new quantitative metric and a skip pyramid context aggregation network (SP-CAN) are proposed to select and enhance ingle-exposure images. Second, an automated exposure selection method is designed to improve the traditional HDR method. A new image quality metric is designed to evaluate captured images, based on which a multiple-exposures selection strategy is developed. Experimental results demonstrated that the first method can achieve 97.6% coverage rate and 0.040 mm measurement accuracy using only 0.6 second, while the second method can achieve a surface coverage rate of 97.4% and measurement accuracy 0.043 mm with only 3-4 exposures averagely (3.3 s).

Keywords: 3D point cloud
Automated exposure selection
Image quality metric
Industrial metrology
Reflective surface measurement
Structured light (SL)
Advisor: Sun, Yu YS
Defining Synthetic Lethal Pathways in ATRT-MYC Tumours

Atypical Rhabdoid Teratoid Tumours (ATRTs) are malignant embryonal brain tumours, of which the ATRT-MYC subgroup are particularly invasive and treatment-resistant with poor clinical outcomes. The purpose of this study is to investigate the cellular effects of the multi-tyrosine kinase inhibitor Dasatinib on ATRT-MYC tumours in vitro, as well as identify and characterize drug compounds that act synergistically with Dasatinib. Here I show that Dasatinib has a cytostatic, but not cytotoxic effect at IC50 concentrations. Proliferative impairment observed is most consistent with senescence and G1/S cell cycle arrest. Vorinostat, a histone deacetylase inhibitor, was found to act synergistically with Dasatinib at near-IC50 doses; combination showed cytostatic effects, with increased senescence markers and impaired cell cycle progression. In conclusion, while Dasatinib and Vorinostat combination did not elicit cell death, it effectively suppressed ATRT-MYC proliferation. Further study of Dasatinib-Vorinostat combination is warranted in vivo as a potential therapy for this highly lethal disease.

Advisor: Huang, Annie A
Reconnecting with One's Lost Self: Experiencing the Emotion-focused Meditation Group Intervention

A qualitative approach was taken to explore the experiences of men who have sex with men (MSM) and who live with HIV (LWH) who participated in the Emotion-Focused Meditation (EFM) group intervention. EFM is an approach to meditation that combines key aspects of Emotion Focused Therapy with an open monitoring form of mindfulness known as Recollective Awareness. Archival audio recordings of group therapy sessions were transcribed and coded using a modified constructivist grounded theory approach to analysis. A core category of Reconnecting with One’s Lost Self: Experiencing the EFM Group Intervention emerged. A hierarchical model of reconnecting with one’s lost self was developed that subsumed all other categories. By extrapolating principles from this model, a theory of Reconnecting with One’s Lost Self was proposed which identifies factors that contribute to reconnecting with one’s lost self. Limitations of the current research are presented along with suggestions for further research.

Keywords: Emotion-Focused Therapy
Grounded Theory
Group Therapy
LGBTQ
Mindfulness
Minority Stress
Advisor: Watson, Jeanne C
Identification and Characterization of Bacterial Isolates that can Enhance Plant Immunity

The ability of soil microorganisms to protect plants has been known for a century and their biotechnological use for crop protection has gained increasing attention. In this study, to identify bacterial strains that can protect crop plants and understand their mechanisms, two bacterial libraries were screened in Arabidopsis thaliana and/or Solanum lycopersicum (tomato) against Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst) DC3000. Through this project, a high-throughput imaging system was developed and in total, 19 bacteria were identified to mitigate disease symptoms. Some of these isolates exhibited direct anti-microbial activity, while other strains did not, suggesting that they induce immunity, termed induced systemic resistance (ISR). In addition, some of the strains showed plant growth promoting effects. Overall, I have established the high throughput method to identify plant immunity-inducing bacteria that can be used for further agricultural biotechnological research.

Keywords: Arabidopsis
crop protection
induced resistance
PGPR
plant immunity
soil microbes
Advisor: Yoshioka, Keiko
Scott, James
Remote Vital Signs Monitoring with Depth Cameras

Remote monitoring of vital signs provides a low-cost, non-intrusive method of assessing an individual’s health. These systems have wide-ranging applications, including detection of patient deterioration in clinical settings and home monitoring of at-risk individuals. This thesis evaluates a novel remote vital signs monitoring system that integrates 3-D depth information and light intensity data to increase tolerance to subject motion. We use 3-D depth analysis and measurement of reflected light intensity due to blood volume variations to estimate heart rate and respiratory rate, two important vital signs. This method achieves a mean error of 1.7 beats per minute for heart rate and 0.05 breaths per minute for respiratory rate. Furthermore, techniques are also described to quantify the severity of motion artifacts, and methods of motion correction are applied to salvage physiological data from noisy signals. Future work will include examining additional data scenarios and improving analysis methods and motion tolerance.

Keywords: depth camera
heart rate
non-contact
remote
respiratory rate
vital signs
Advisor: Levi, Ofer
Mihailidis, Alex
The Role of Heat Shock Proteins in the Repeated Bout Effect

Subjecting skeletal muscle to a few lengthening contractions (LCs) prior to a subsequent greater number of LCs results in a phenomenon known as the repeated bout effect (RBE). Only a few LCs increases αβ-crystallin, HSP25 and HSP72, suggesting these HSPs may play a role in the RBE. TA muscles from male Sprague-Dawley rats were preconditioned with either 0, 5 or 15 LCs prior to 60 LCs. Preconditioning with 15 LCs significantly elevated skeletal muscle αβ-crystallin (p

Advisor: Locke, Marius
(Re)Negotiating the Centre: A Qualitative Study Exploring the Black Community's Attitudes Towards Culturally Integrative African Healing Traditions and Western Psychotherapeutic Systems

The increased interest and use of holistic and traditional healing systems among diverse groups have inspired a demand for culturally integrative mental health treatments and research. This study used a postcolonial lens to explore how Canada’s African descendants might respond to a psychotherapeutic approach that culturally integrates African healing traditions (AHT) and Western systems. Ten participants were recruited for semi-structured interviews. The data were thematically analyzed using a grounded theory approach, and a mid-level theory was proposed. The findings indicated that the participants’ attitudes and experiences with AHT systems and Western psychotherapy influenced their attitudes and receptiveness towards interventions that aim to culturally integrate AHT and Western systems for psychotherapeutic purposes. Implications for clinical practice and theory were provided, along with recommendations for future research.

Keywords: African Diaspora
African Healing Traditions
Critical Mental Health
Culturally Integrative Psychotherapy
Multicultural Psychotherapy
Western Counselling and Psychotherapy
Advisor: Moodley, Roy
Regulation of Transporters in Human Placental Trophoblast Cell Lines

Pronounced inflammation or infection associated changes in the expression of many key placental transporters has been observed in human and rodent disease models, which are attributed to pro-inflammatory cytokines. Many infections and chronic inflammatory states are associated with activation of TH-17 and release of IL-17A and IL-23. However little is known about the impact of TH-17 associated cytokines on the expression of placental transporters. We observed a 50% decrease in the mRNA levels of BCRP and OATP2B1 in IL-23-/ IL-17-treated BeWo cells, while IL-17 reduced the mRNA levels of OATP2B1 and OAT4 by half in JAr cells. In BeWo cells, IL-17-/ IL-23-mediated downregulation of BCRP and OATP2B1 were attenuated by NF-kB and MAPK inhibitors. Similarly, IL-17-mediated downregulation of OATP2B1, but not OAT4, was attenuated with the NF-kB and MAPK inhibitors in JAr cells. These results suggest the placental transporter dysregulation caused by TH-17-associated cytokines is mediated through NF-kB pathway.

Keywords: ABC transporters
Inflammation
NF-kB
p38 MAPK
TH-17 cytokines
Advisor: Piquette-Miller, Micheline MPM
Docetaxel Loaded Nanobubbles for Ultrasound Triggered Antivascular Therapy and Localized Drug Delivery

Docetaxel is a chemotherapeutic drug that plays an essential role in breast cancer therapy but exhibits suboptimal pharmacokinetic profiles with limited accumulation in tumours. In this thesis, ultrasound-stimulated, docetaxel-loaded nanobubbles are proposed to achieve localized drug delivery and induce antivascular therapy towards synergistic anti-tumour efficacy. Drug-loaded nanobubbles were synthesized via a precursor-lyophilization method. The drug loading capacity was found to increase with lipid concentration. DTX-NBs were formed with a mode diameter at ~230 nm, loaded with ~104 μg of docetaxel on ~1010 bubbles per ~0.4 μL of gas. Ultrasound cavitation facilitated the release of docetaxel and demonstrated comparable cytotoxicity to the commercial docetaxel formulation (i.e. Taxotere®) on mouse breast cancer cells. Ultrasound-stimulated nanobubbles were shown to induce acute blood flow reduction in the tumour center on Balb/c mice, indicating successful in vivo vascular shutdown due to nanobubble cavitation. These drug-loaded, ultrasound-responsive nanobubbles show high potential for increased anti-cancer efficacy.

Keywords: cancer
docetaxel
nanobubble
ultrasound
Advisor: Matsuura, Naomi Dr.
Capturing Heightened Impulsivity In Adolescent Mice using A T-Maze Delay Discounting Task

Delay discounting is a well-established measure of heightened impulsive decision-making during adolescence. The VTA and mPFC are implicated in delay discounting and undergo developmental alterations during adolescence. It remains elusive, however, as to whether the functional maturation of this circuit underlies age-dependent changes in delay discounting. In this study, we used a T-maze delay discounting task and found C57BLK6/J wildtype adolescent mice to exhibit steeper delay discounting than adults with a five second delay contingency. This difference in impulsivity was not driven by age-dependent abilities in cognitive and behavioural flexibility. To measure in vivo calcium signaling in dopaminergic VTA axons in the PL during delay discounting decision-making, we injected a Cre-dependent calcium sensor in TH-cre animals and saw no terminal viral expression after thirty days. Furthermore, TH-Cre adolescent animals exposed to deep anaesthetic ketamine did not exhibit heightened impulsivity compared to adult counterparts.

Keywords: adolescence
delay discounting
dopamine
impulsivity
medial prefrontal cortex
ventral tegmental area
Advisor: Arruda-Carvalho, Maithe
Investigating the Effects of Cranberry Proanthocyanidin and its Microbial Metabolites on the Human Intestinal MiRNome In Vitro

The molecular basis underlying the known anti-inflammatory and anti-carcinogenic properties of cranberries is incompletely understood. The objectives of this project were to determine microRNA signatures of Caco-2BBe1 cells in response to a cranberry proanthocyanidin-enriched extract and two of its gut microbial metabolites, 3,4-dihydroxyphenylacetic acid and 3-(4- hydroxyphenyl)-propionic acid, evaluate if they were maintained in an inflammatory environment, and assess if the treatments mitigated inflammatory microRNA signatures. Each treatment generated a distinct microRNA signature, but the metabolites shared a “core” microRNA response. Treatment signatures were disrupted following IL-1β challenge, but the extract and 3,4- dihydroxyphenylacetic acid partially reversed microRNAs upregulated by IL-1β. Gene targets of microRNAs altered by the metabolites, but not the extract, were significantly enriched in many pathways relating to cell growth and development and pathways in cancer. Conclusively, the health effects of cranberry could be mediated via host microRNA and the gut microbiome may be indispensable to its bioactivity.

Keywords: cranberry
metabolites
microRNA
polyphenols
proanthocyanidin
Advisor: Comelli, Elena M
Progress Towards the De Novo Design of a Novel Protein Secondary Structure

Nature has sampled a very small fraction of the protein sequence space through evolutionary processes. The structures that these sequences adopt are relegated to permutations of just a few secondary structures. In fact, there are only two types of ‘regular’ secondary structures – the α-helix and β-sheet, although other types of non-regular secondary structures and random coils do exist. We hypothesized that novel secondary structures may exist in the unsampled space. To test this, we conceived of a spiral shaped secondary structure element not seen in nature. We created in-silico structural models and found amino acid sequences best predicted to stabilize the models. We synthesized designs and used CD and NMR spectroscopy to validate that our novel spiral secondary structure self assembles with an RMSD of ~4.5Å to the in-silico design. This study offers the first glimpse into a potentially vast world of undiscovered secondary structures.

Keywords: computational biology
de novo protein design
molecular dynamics
NMR
novel structure
Advisor: Garton, Michael