VictorJuiz/thesis huggingface dataset:
Development of an MRI-guided Robotic Platform and Optimized Treatment Parameters for Sonothrombolysis of Intraventricular Blood Clots

Intraventricular haemorrhage develops in 3% of all live births in Canada and 50% of those babies develop post-haemorrhagic ventricular dilatation due to blood clots in the ventricles. This often leads to hydrocephalus, which can negatively impact an infant’s vision, hearing and long-term neurodevelopment. Current treatment involves invasive brain surgery that relieves the built-up pressure from hydrocephalus, but the clot is often left untreated. In this thesis, a robotically controlled focused ultrasound platform was evaluated as a method to perform sonothrombolysis of the clot. A range of focused ultrasound parameters were tested in vitro with porcine blood to determine what values effectively and efficiently induced sonothrombolysis. The robot’s current state was assessed and necessary changes to the hardware and software were implemented to bring the robot to a working condition. The thesis concludes with a robotically controlled focused ultrasound platform along with a set of optimized parameters recommended for sonothrombolysis.

Keywords: cavitation
focused ultrasound
intraventricular hemorrhage
thrombolysis
Advisor: Drake, James
Waspe, Adam
A Filamin A Binding Protein Regulates Vimentin Assembly and Cell Extension Formation

The actin and intermediate filament cytoskeletons are critical polymer networks that contribute to important pathological processes. Some of these processes involve the generation of cell extensions, which enable remodeling of the extracellular matrix and invasion of the matrix by malignant tumors. Currently the mechanisms by which the actin and vimentin cytoskeletal systems functionally interact to mediate cell extension formation and matrix invasion are not defined. I hypothesized that the actin binding protein filamin A, enables vimentin intermediate filament assembly, thereby enhancing the formation of cytoplasmic extensions. In cultured fibroblasts, shRNA knockdown of filamin A reduced the formation of cell extensions by >4- fold; siRNA knockdown of vimentin resulted in >4-fold shorter cell extensions. Vimentin filament assembly was enhanced in cells expressing filamin A, suggesting a potential functional interaction between these two proteins.

Advisor: McCulloch, Christopher A
In-situ Electrochemical Characterization of Ni and Amorphous Ni-based Nanoparticles in an Anion Exchange Membrane Water Electrolyser

Alkaline water electrolysis has regained interest as a promising technology for converting renewable energy into H2 due to the recent developments in anion exchange membranes. In this study, an anion exchange membrane water electrolyser (AEMWE) was fabricated to study the in-situ electrocatalytic performance of Ni-based materials. Ni is of particular interest due to its wide availability and intrinsic activity. Commercial Ni and amorphous (Ni, Co)-Nb-Y nanoparticles (NPs) were applied to AEMWE as electrocatalysts showing promising performance. Amorphous (Ni, Co)-Nb-Y NPs were produced through a novel two-step ball milling process. Fabrication methods (i.e. membrane electrode assembly (MEA) hot-pressing and optimized ionomer content) were critical for improving cell performance. AEMWE operating conditions (i.e. temperature and MEA compression) were investigated to enhance activity. The concentration of a supporting electrolyte dramatically increased the cell performance. Electrochemical testing showed that Ni displayed higher in-situ activity than the amorphous alloys. Cycled amorphous catalyst layers were more stable.

Keywords: AEM
electrolyser
electrolysis
nanoparticles
nickel
water
Advisor: Thorpe, Steven J
Elucidating the Molecular Mechanism of FZD5 Essentiality in RNF43 mutant Pancreatic Cancer

Abstract Our laboratory recently identified FZD5 as the sole essential FZD, out of ten human FZD receptors, in RNF43 mutant pancreatic cancers. My work explores two hypotheses behind this finding. First, we hypothesized that FZD5 is the preferential RNF43 substrate. Alternatively, FZD5 may preferentially recognize the Wnt ligand involved in PDAC, and as such RNF43 mutations lead to increased activity of this Wnt-Frizzled signalling circuit. I quantified FZD levels in control cells and in cells harbouring a RNF43 mutation and and observed a broad negative regulation role for RNF43 towards FZD receptors. Then I examined the role of FZD5 as the main FZD responsible of transmitting endogenous Wnt signalling in pancreatic cancer. There, I obtained evidence that the N-terminus ligand binding domain of FZD5 was required for the growth of PDAC cells. Together, my work highlights that the FZD5 essentiality can be attributed to preferential FZD receptor-Wnt ligand selectivity.

Advisor: Angers, Stephane
Vanadium Dioxide Phase Transition Modeling and Bias Control for Photodetection

Vanadium dioxide (VO_2) is a transition material that demonstrates phase transitions between the insulator and metallic states when under thermal, electrical or optical stimuli. It is a promising material for novel devices, for instance, switches, volatile memory, oscillatory neural network units, and photodetectors. Despite being a long-standing interest in the field of condensed matter physics, the numerous observed properties of VO_2 remain insufficiently explained, which impedes the progress of its utilization for electronic devices. This thesis develops theoretical explanations and corresponding analytical and numerical models that fit our fabricated VO_2 devices. This thesis also investigates the feasibility of utilizing VO_2 as photodetectors and develops a bias control circuit with low-cost off-the-shelf circuit components, enabling repeated operations despite the hysteresis effect, demonstrated the potential of VO_2 to be integrated with existing electronics.

Keywords: Vanadium Dioxide
Advisor: Poon, Joyce
Modified Biomass Carbons for Electrochemical Capacitor Electrodes

The demand for energy storage devices has led to the increased development of cost-effective and sustainable electrode materials for electrochemical capacitors (ECs). This project investigated low-cost biomass waste pinecone to produce activated carbon (AC) and biochar in comparison with commercial coconut shell-based AC (YP-50F) as EC electrode materials. Pinecone-based AC produced via KOH chemical activation demonstrated a gravimetric capacitance of 214 F g-1¬ (at 50 mV s-1 in acidic media). Biochar (Flashed pinecone) synthesized without KOH showed a good capacitive performance at the same rate. Nitrogen doping was used to introduce pseudocapacitance in both ACs and led to an improvement in gravimetric capacitance at 50 mV s-1 for doped YP-50F (154 F g-1). Good rate capacitance retention was achieved in doped YP-50F (62.5 %), doped pinecone-based AC (60.0 %), and Flashed PC (78.1 %). This showed the promise of pinecone as a feedstock for low-cost, sustainable electrode materials.

Advisor: Lian, Keryn K.
Bio-functional Analysis of Ubiquitin Ligase UBE3D

The ubiquitin system is comprised of a reversible three step process: E1 activating enzyme, E2 conjugating enzyme and an E3 ligase, leading to ubiquitin molecules being post-translationally modified onto substrate proteins leading to a plethora of downstream effects (localization, function and half-life). UBE3D, a HECT (homologous to E6-AP carboxylic terminus) E3 ligase, has a relatively elusive regulatory role within the cell. Here, we systematically analyze and characterize UBE3D as well as its highest confidence interactor, Dynein axonemal assembly factor (DNAAF2) through: Autoubiquitylation assay; intracellular localization with immunofluorescence; interaction network using proximity-dependent biotin identification (BioID) to better understand the relationship of these two proteins. DNAAF2 protein interaction mapping allowed for insight into PIH domain. In summary, I have used multiple approaches to gain novel knowledge and insight into the potential functional role of UBE3D within the cell, and its putative partner protein, DNAAF2.

Keywords: Cilia
DNAAF2
Dynein
Mass Spectrometry
UBE3D
Ubiquitin
Advisor: Raught, Brian
Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Alveolar Epithelial Type II Cells

AECIIs, local progenitors of alveoli, differentiated from human iPSCs may provide a therapeutic potential for lung diseases. However, existing differentiation protocols lack in yield and purity, and maturity lacking their functions. Transforming 3D to 2D culture conditions at crucial development phase of lung bud organoids will enhance differentiation, stability and functionality of the iPSC-derived AECIIs. The lung organoids differentiated from human iPSCs were dissociated and matured to yield highly homogeneous population of AECIIs. The AECIIs were then purified and propagated. Cells were then tested for functionality to investigate their maturity. We produced highly proliferative AECIIs verified by expression of epithelial cell adhesion molecule and presence of surfactant protein C and lamellar bodies. The functionality of the iPSC-derived AECIIs was confirmed by release of soluble We improved existing methods to differentiate human iPSCs into functional AECIIs for a greater production capacity, which provides a powerful tool for regeneration research.

Keywords: Acute respiratory distress syndrome
differentiation
pluripotent stem cells
regenerative medicine
stem cell
Type II alveolar epithelial cells
Advisor: Zhang, Haibo
Monolithically Integrated FDSOI CMOS Electron-and Hole-quantum Dot Qubits and Readout Electronics for Large-scale Quantum Computing Processors

This thesis investigates the application of nanoscale CMOS and millimeter-wave (30 – 300 GHz) electronics towards scalable, “high” temperature (1 – 4 K) quantum computing processors with electron or hole semiconductor quantum dot qubits integrated with their control and readout electronics on the same die. It was found that, at 2 K, the Si n-MOSFET and SiGe p-MOSFET of a commercial FDSOI CMOS process could be used as either quantum dots when biased in subthreshold or as high RF performance transistors when biased in the saturation region, with the p-MOSFET performing as the better quantum dot showing Coulomb blockade up to 50 K. MOSFET S-parameter measurements showed that they have better performance at 2 K than at 300 K, suitable for spin manipulation circuits. A qubit readout transimpedance amplifier operating at 2 K was designed using a room temperature model-based methodology and manufactured with the qubits.

Advisor: Voinigescu, Sorin P
A Finite Element Model for Laser Interstitial Thermal Therapy Near Large Vessels for Lung Tumor Treatment Planning

A finite element analysis was conducted to characterize the impact of the heat sink effect due to large vessels near the ablation area in laser interstitial thermal therapy of lung cancer. The model consists of a 1 cm in diameter tumor near a large vessel with properties resembling those of the secondary branches of the pulmonary artery. A parametric sweep of different laser power inputs was performed and the light, thermal, and tissue damage distributions were evaluated. Comparative simulations in liver and brain tissue were carried out to better characterize the lung tissue’s unique response. The simulation results conclude that the lung’s unique properties, specifically its relatively low density and low optical penetration, may be favorable when treating near vascular heat sinks as compared to other tissue types.

Keywords: Finite Element Model
Heat Sink Effect
Laser Interstitial Thermal Therapy
Lung Cancer
Advisor: Yasufuku, Kazuhiro
Unearthing Invasion Mechanisms: Do Plant-soil Feedbacks Facilitate the Invasions of the Dog-strangling Vine?

Human welfare is gravely threatened by invasive species. One of Canada’s most invasive plant species, Vincetoxicum rossicum (DSV), often creates virtual monocultures. Below-ground interactions are important in determining the success and impact of plant invasions. I hypothesized that DSV invasion benefits from plant-soil feedbacks; that is, DSV will outperform competitors in soils which it has already invaded. A four-factor (soil invasion level, sterilization, activated carbon, and species) growth chamber experiment with a randomized complete block design was conducted to disentangle potential plant-soil feedbacks. In addition, soil chemical properties (i.e., nutrients) were analyzed to identify potential confounding effects. Overall, the effects of soil treatments were species-specific, and there was a lack of evidence supporting the hypothesis that DSV invasion benefits from plant-soil feedbacks. However, nitrogen was more abundant in invaded soils, suggesting that the impact of DSV invasion may instead be mediated by its altering of the soil nutrient dynamics.

Keywords: dog-strangling vine
invasive species
plant-soil feedback
Advisor: Cadotte, Marc
Improving Pre-operative Cefazolin Use in Patients with Reported Beta-Lactam Allergy Undergoing Elective Surgery

Cefazolin is the preferred agent for antimicrobial prophylaxis in most surgical procedures but is often avoided in patients who report an allergy to a beta-lactam antibiotic. A retrospective cohort study was conducted to assess the relationship between self-reported beta-lactam allergy and surgical site infection (SSI). Using a multivariable logistic regression model, a reported beta-lactam allergy was associated with a significant increase in SSI risk (adjusted odds ratio 1.61, 95% CI: 1.04 - 2.51, p = 0.03) completely mediated by receipt of an alternate antibiotic to cefazolin. An anesthesiologist-led intervention consisting of a standardized allergy and antibiotic selection algorithm was implemented in January 2019 which resulted in a sustained increase in pre-operative cefazolin use in patients with reported beta-lactam allergy (42.7% to 85.6%; p=0.002). Due to its simplicity and minimal resource requirements, this intervention is scalable to other institutions with potential to reduce SSI risk across a broad number of surgeries.

Advisor: Leis, Jerome A
Comparative Transcriptomics in the Parasitic Plant Genus Cuscuta Reveals the Effects of Ploidy Level on Gene Expression

Polyploidy is known to influence the rapid evolution observed in angiosperms because it can spark near instantaneous divergence among species. My study system, Cuscuta section Denticulatae, involves two diploid progenitor species, C. denticulata and C. nevadensis, and two relatively recently formed allotetraploids, C. veatchii and C. psorothamnensis. Both parental species are further distinguished into genotypic forms labeled as D1, D2 and N1, N2, respectively. In C. denticulata, autotetraploid populations from D1 have been previously identified. Transcriptomes of both parents were assembled and annotated. To investigate the effects of gene dosage in this system, the transcriptomes were analyzed for differentially expressed genes within each parental species, including between diploid and autotetraploid populations. Differential gene expression was observed between forms D1 and D2 in C. denticulata, with a bias in gene upregulation in D1. Also, a comparative orthologue analysis found a high degree of similarity between the parents and their forms.

Keywords: Cuscuta
Hybridization
Parasitic plants
Polyploidy
RNA-seq
Transcriptome
Advisor: Stefanović, Saša
Visualizing Protein-Protein and Gene Regulatory Networks in Arabidopsis thaliana

Protein-protein interaction networks (PPNs) and gene regulatory networks (GRNs) visualize protein-binding and gene regulation respectively. Advancements in screening technologies such as enhanced yeast-one-hybrid and protein binding predictions have allowed for high throughput determination of such networks. Currently, Arabidopsis-based GRN and PPN viewers are restricted to ad-hoc networks and do not link out to external sources. I created two interactive web-based viewers, Arabidopsis Interactions Viewer 2.0 (AIV2) and Arabidopsis GEne Network Tool (AGENT) to visualize PPNs and GRNs respectively. Features include dynamic interaction filtering, uploading and downloading network data, subcellular-focused network layouts, and loading Bio-Analytic Resource’s (BAR) expression data onto genes. Data visualization principles are applied such as rapid serial visual presentation (RSVP) and Shneiderman’s mantra of details-on-demand. Moreover, AGENT is a framework for GRN curation which allows future expansion. Lastly, I demonstrate how to use these tools for hypothesis generation.

Keywords: Data Visualization
Gene Regulatory Networks
Plant Biology
Protein Protein Interaction Networks
Systems Biology
Web Development
Advisor: Provart, Nicholas J
On the Design and Development of a Self-Driving Car for the SAE AutoDrive Challenge

The SAE AutoDrive Challenge is a three-year collegiate competition to develop a self-driving car by 2020. The first year of the competition was held in May 2018 in Yuma, Arizona. This first installment required teams to perform lane keeping and avoid static obstacles without a detailed prior map of the course. The second year was held in June 2019 at MCity, a mock town built for self-driving testing at the University of Michigan. Teams were required to navigate a series of intersections while handling dynamic pedestrians, traffic lights, and traffic signs. aUToronto is U of T's competition team and our self-driving car, Zeus, was the winning entry. This thesis provides a system description of Zeus at the Year 1 and Year 2 competitions. This thesis also describes the specialized lane detection system developed for Year 1 and the lightweight object detection and tracking system that was developed for Year 2.

Keywords: Autonomous Vehicles
Autonomy
Computer Vision
Perception
Robotics
Self-Driving Vehicles
Advisor: Schoellig, Angela P
An Observational, Mixed-design, Exploratory Study Evaluating Cognitive Function and Structural Deficits in Seasonal Affective Disorder

Introduction: Seasonal Affective Disorder (SAD) presents a naturalistic model of depression in order to investigate changes to neural structure and cognition, which is difficult to investigate in Major Depression due to a variable treatment response. Methods: Healthy controls (N=17) and SAD patients (N=17) had their cognitive function evaluated over the summer and winter. A subset of 20 participants also underwent structural imaging. Results: There was widespread significant cortical thinning to the frontal lobe and significant volumetric reductions to the globus pallidus in SAD patients during the winter and summer Cognitive domains, including set-shifting, psychomotor speed, and executive function, were impaired in SAD over the summer months but not winter months. Discussion: The structural deficits form key nodes within the limbic system and are responsible for top-down regulation of mood and some cognitive functions. SAD cognitive deficits in the winter may have been masked by cognitive fluctuations exhibited by healthy participants.

Keywords: Cognition
Depression
Morphometry
Seasonal Affective Disorder
Advisor: Lipsman, Nir
O6- Methylguanine DNA Methyltransferase Activatable Photosensitizers for Cancer Therapeutics

Photodynamic therapy (PDT) is minimally invasive medical procedure used for treatment of various cancers. PDT uses a small molecule photosensitizer (PS) that, when in the presence of molecular oxygen and light, can produce reactive oxygen species (ROS) that are toxic to cells. Over the past few years researchers have aimed to increase PDT cell specificity. Adding a secondary form of activation other than irradiation allows for disease-feature targeting, reducing off target effects. Enzyme-activatable PSs are one approach to add selectively over healthy tissues. In this study two novel O6-methylguanine-DNA methyltransferase (MGMT) activatable photosensitizers were synthesized and their fluorescent profiles were characterized in in vitro enzyme studies. These scaffolds provide the necessary foundational work for studies to continue in cells, as well as for development of future modifications on the same molecular backbone.

Advisor: Kanelis, Voula
Beharry, Andrew
Evaluation of the Impact of Remote Titration Combined with Telemonitoring on the Optimization of Guideline Directed Medical Therapy for Patients with Heart Failure

To improve health outcomes in heart failure patients, guideline directed medical therapy (GDMT) should be optimized to maximal tolerated doses. However, GDMT remains underutilized, with less than 25% of patients receiving target doses in clinical practice. The objective of this research was to determine the effectiveness of remote titration facilitated by telemonitoring and identify factors that promote or impede remote titration. A randomized controlled trial (N=108) was designed to compare a remote titration strategy with a standard titration program. Analysis of a pilot cohort of 42-patients found that telemonitoring increased the proportion of patients that achieved target doses (90.5% vs. 52.4%), decreased time to dose optimization (12.26 vs. 19.01 weeks), and reduced the number of clinic visits by 50%. Facilitators to remote titration included the ease-of-use and utility of the intervention while barriers included the resources and funding required. This study provided evidence that remote titration can be effectively facilitated by telemonitoring.

Keywords: GDMT
Guideline Directed Medical Therapy
Heart failure
Telemonitoring
Titration
Advisor: Seto, Emily
Using a Model-guided Approach to Design and Characterize Strains of Escherichia coli Producing cis,cis-Muconic Acid

Adipic acid is an industrially important chemical produced using petrochemical feedstocks. Adipic acid and its direct precursor cis,cis-muconic acid are therefore interesting targets for microbial production in hosts such as Escherichia coli. While rational engineering strategies have been shown to produce high-performance strains for muconic acid production, computational strategies may predict non-obvious growth coupling strategies. In this study, constrained minimal cut sets were used to predict a growth-coupled strategy for muconate production in E. coli. Various background strains and plasmids were constructed, containing gene knockouts and heterologous pathway enzymes, respectively. All strains were characterized at the plate reader and shake flask levels, showing reasonable production yields for muconic acid intermediates. The highest-performing strains were characterized using bioreactors. By yield, rational designs performed best in shake flasks, while computational design performed best in bioreactors. Additionally, sub-milligram titers of adipate were produced in a rationally designed strain by addition of enoate reductase.

Keywords: adipic acid
flux balance analysis
metabolic engineering
minimal cut sets
muconic acid
Advisor: Mahadevan, Radhakrishnan
PIK3CAH1047R and PIK3CB Isoforms of PI3K-signalling Mediate Distinct Signalling Pathways during Transformation of Mammary Epithelial Cells

Mutations in PIK3CA are observed in 20-42% of breast cancers, in contrast PIK3CB is rarely mutated. Rather, amplification of the wildtype PIK3CB occurs in a small subset (1.6%) of breast tumours. Here, we investigated the isoform specific activities of p110αH1047R and p110β during transformation of MCF-10A mammary epithelial cells. Overexpression of p110αH1047R and p110β, respectively, induced distinct morphological and molecular characteristics, and invoked distinct molecular programs of EMT. Whereas p110β depended on Rac1 to induce a motile and invasive mesenchymal phenotype, p110αH1047R induced SNAIL and a cadherin switch, characteristic of EMT. Furthermore, p110β overexpression induced genome instability and decreased proliferation through cell cycle arrest and a senescence like phenotype, which could be overcome by genetic knockdown of TP53. These findings revise our understanding of the role of PIK3CB in breast cancer, and suggest that Rac1 and TP53 may provide important axes for establishing transformation in cells with amplification of PIK3CB.

Keywords: epithelial-to-mesenchymal transition
p53
PI3K-signalling
PIK3CB
Rac1
senescence
Advisor: Hamel, Paul A.