VictorJuiz/thesis huggingface dataset:
Analyzing Industry Cloud-computer-aided Design (CAD) Behaviours to Enhance Teaching Practices

Introduced in the 1960s, computer-aided design (CAD) has become an essential tool in an engineer’s repertoire. Since its inception, CAD has seen emerging breakthroughs in the form of cloud-CAD which allows for greater control and management over the design process. Despite these innovations, we continue to teach CAD focusing on traditional practices.To modernize how CAD is taught, we propose learning from industry CAD users. Through a qualitative study, we interview industry users about the responsibilities and challenges of adopting cloud-CAD. Subsequently, we take a quantitative approach by collaborating with an industry partner and retrieving their server analytics. Through a statistical analysis, we aim to identify underlying behaviours and patterns. Through this joint approach, we can better understand the expectations newly graduated engineers will encounter upon entering the workforce; with this information, we can tailor the CAD teaching practices to best meet student needs.

Advisor: Olechowski, Alison
A Low-power Injection-locked O-QPSK/8PSK Transmitter

Low-power constant-envelope modulations have gained popularity to meet the increasing demand for efficient transmitters with high data rates. In this thesis, a novel architecture for a low-power wireless transmitter is studied. The idea of employing a single injection-locked frequency divider (ILFD) to perform phase modulation is brought forth. The proposed solution, tailored to Offset-Quadrature-Phase-Shift-Keying (QPSK) and 8PSK for various applications such as IoT (Internet of Things), has been realized by exploiting the property of an ILFD to work as a phase rotator. The output is coupled to the antenna via a transformer to deliver the desired power. The highly efficient, high-bandwidth OQPSK and 8PSK transmitters are capable of operating at up to 120 Mbit/s and 136 Mbit/s, with output powers of 1.3 mW and 3 mW respectively and system efficiencies above 30%. The paper on the OQPSK transmitter has won the "Best Young Scientist Paper Award" in ESSCIRC 2018.

Keywords: 8PSK
Injection-locked-divider
IoT
Low-power transmitter
OQPSK
Quadrature oscillator
Advisor: Liscidini, Antonio
The Role of Endothelial-specific Autophagy-related Protein 7 in Doxorubicin-induced Cardiotoxicity

Doxorubicin (DOX) is an effective, broad-spectrum antineoplastic agent with serious cardiotoxic side effects. Recent evidence has linked the dysregulation and destruction of the endothelium in the development of DOX-induced heart disease. Autophagy is an important pro-survival mechanism to recycle and remove damaged cellular constituents. Autophagy-related protein 7 (ATG7) catalyzes autophagosome formation, a critical step in autophagy. In this study, we used endothelial cell-specific Atg7 knockout (EC-Atg7-/-) mice to characterize the role of endothelial cell-specific autophagy in DOX-induced cardiotoxicity. DOX-treated EC-Atg7-/- mice showed reduced survival and a greater decline in cardiac function compared to wild-type controls. Histological assessments revealed increased cardiac fibrosis in DOX-treated EC-Atg7-/- mice. DOX-treated EC-Atg7-/- mice had elevated serum levels of creatine kinase-myocardial band, a biomarker for cardiac damage. Thus, endothelial cell-specific autophagy represented a protective pathway against DOX-induced cardiotoxicity.

Keywords: Autophagy
Cancer Therapy
Cardiovascular Sciences
Heart Failure
Mouse Study
Advisor: Verma, Subodh
Modulation of P300 Acetylation to Protect Against Doxorubicin-induced Cardiotoxicity

Doxorubicin is amongst the most widely prescribed chemotherapy drugs, although progressive use increases the risk of heart failure due to cardiotoxicity. In one mechanism, doxorubicin induces cardiomyocyte (CM) death mediated by the tumour suppressor, p53. Currently, there are no preventative treatments for doxorubicin-induced cardiotoxicity, although a number of therapies are being evaluated. To induce CM death, p53 requires acetylation by the histone-acetyltransferase protein, p300. Therefore, we hypothesize that p300-mediated inactivation of p53 protects against doxorubicin-induced cardiotoxicity. In vitro, we evaluated markers of p53 activation, DNA damage, and apoptosis. For experiments in vivo, we assessed survival, heart function, and cardiac tissue morphology. In vitro, p300 inhibition led to reduced p53 activation, DNA damage and apoptosis. In vivo, p300 bromodomain inhibition reduced mortality and improved heart function. These results demonstrate a novel targeted therapy to address the growing issue of doxorubicin cardiotoxicity and may potentiate a new drug for clinical use.

Advisor: Connelly, Kim A
Singh, Krishna K
Evidence for Fc Gamma Receptor Inhibition in the Therapeutic Activity of CD44 Antibodies in a Murine Model of Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by low platelet counts. In a murine ITP model, thrombocytopenia has previously been treated using CD44 antibodies, although the mechanism of effect is not well understood. This thesis demonstrates that a monoclonal CD44 antibody can inhibit platelet phagocytosis in vitro and ameliorate murine ITP. A requirement for a functional Fc region was observed, as F(ab)’2 and deglycosylated anti-CD44 were not therapeutic. Furthermore, anti-CD44 (IgG1) could only inhibit platelet phagocytosis and ameliorate ITP in vivo when an IgG1 anti-platelet antibody was utilized, and not IgG2a. This subtype specific effect indicates that the anti-CD44 was therapeutic when able to interact with the same subclasses of Fc gamma receptors (FcyRs) as the anti-platelet antibody. Thus, binding to FcyRs, using their Fc region, and inhibiting the activating FcyR pathway of platelet destruction may potentially explain how CD44 antibodies inhibit platelet phagocytosis and ameliorate murine ITP.

Keywords: CD44 Antibodies
Immune Thrombocytopenia
IVIg
Murine Model of ITP
Advisor: Lazarus, Alan H
Community Engagement Practices at MLSE Launchpad

Sport-for-development (SFD) organizations increasingly deliver programs in marginalized communities within the Global North. Despite this growth in programming, and significant academic attention towards this trend, studies of the methods through which SFD organizations receive input from and engage with communities have been largely absent. The purpose of this study was to explore how Maple Leafs Sports and Entertainment Launchpad, an SFD centre in downtown Toronto recruits in and relates to the surrounding Moss Park community. Data collection consisted of semi-structured interviews with nine staff, and observations over four months at Launchpad and its external community events. The main results were as follows: a significant group of participants were attracted to the space through non-sport activities, despite previous focuses on sport recruitment; Launchpad provided a number of “extras” that filled in fundamental gaps in public services; and important distinctions between the language of “engagement” and “recruitment” among staff emerged.

Keywords: community engagement
corporate social responsibility
development
sociology
sport
sport-for-development
Advisor: Darnell, Simon
Kinetics of Neutrophil Recruitment and their NF-κB Response to Neisseria gonorrhoeae Uterine Infection

Neisseria gonorrhoeae (Ngo) is the bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Aside from the cervicitis typical of gonococcal infection in women, untreated infections may ascend into the upper genital tract, leading to a devastating inflammatory response that can result in pelvic inflammatory disease. In this thesis, I reveal the first leukocyte responders to Ngo uterine infection using a transgenic mouse model that expresses green fluorescence protein (GFP) when the immediate-early transcription factor NF- κB is activated. Using flow cytometry, my results demonstrate recruitment of neutrophils into the infected uterus, where only a subset of these neutrophils displays activated NF-κB, and most of which are not associated with gonococci, suggesting that these populations may represent different neutrophil phenotypes. These findings make it enticing to consider that the responding neutrophils are of a phenotype incapable of clearing infection, and may help explain persistent colonization observed in untreated individuals.

Keywords: female reproductive tract
Neisseria gonorrhoeae
neutrophils
NF-κB
pelvic inflammatory disease
Advisor: Gray-Owen, Scott D
Extract and Component-Specific Allergen Recognition Patterns in Canadian Children: Insights into Preschool Asthma and Nut Allergy

The early presence and diversity of allergic sensitization is a risk factor for the development of asthma and a diagnostic marker for allergy. Assessing IgE sensitization at the allergen extract and protein component level may increase specificity by providing insights into allergen protein families involved and thereby improve predictions of clinical relevance of sensitization. Using a comprehensive multiplex IgE test, we characterized sensitization profiles in a cohort of preschool asthmatics and identified potential allergen biomarkers (Ara h 1, 2, 3, 6, Fel d 1, and Can f 1) that were associated with more severe asthma. We also identified allergen components that may be able to improve specificity of peanut and tree nut allergy diagnosis in this pediatric population (Ara h 1, 2, 6, Cor a 14, Jug r 1, Ana o 3). Lastly, we generated models that allow the comparison and conversion of specific IgE-levels measured using different testing platforms.

Keywords: allergic sensitization
allergy
asthma
component resolved diagnosis
IgE
Advisor: Eiwegger, Thomas
Defining the Role of the Histone 3.3 (H3.3G34R) Mutation in the Pathogenesis of Pediatric High Grade Astrocytoma

Pediatric high-grade astrocytoma (pHGG) is the leading cause of brain tumour related death in children. Approximately 15% of hemispheric pHGG have a mutations in the H3F3A gene, leading to a glycine-arginine substitution (H3.3G34R). A novel proteomics-based strategy, BioID, to investigate the H3.3G34R-associated changes in the histone interactome. H3.3G34R mutation lead to alterations in the histone H3.3 interactome including chromatin modifiers and DNA repair proteins. Expression of H3.3G34R in normal human astrocytes increased sensitivity to radiation and a delayed double stranded break repair kinetics as determined by neutral comet assay. H3.3G34R lead to loss of homologous recombination specific RAD51 recruitment in response to radiation and a compensation through the error prone 53BP1 specific non-homologous end joining pathway. Our data suggest that H3.3G34R mutation leads to dysregulation of the histone code and may induce genomic instability through loss of function in the DSB repair pathway and may provide a novel avenue of therapeutic vulnerability.

Advisor: Hawkins, Cynthia E
Optimization of Murine Pancreas Decellularization to Obtain ECM for a Co-Culture System Capable of Producing Mature Pancreas Cell Types

Maturation and cell organization have remained issues for in vitro pancreatic tissue engineering. However, many culture conditions do not incorporate the extracellular matrix (ECM), an element crucial to organogenesis. This project aimed to create a 3D co-culture system with murine ECM. To obtain ECM, optimization of decellularization was explored using perfusion of whole pancreas or lobe as well as by using soak-agitation for slices. The detergents Triton X-100, CHAPS and SDS were tested. ECMs were analyzed for DNA content and retention of critical ECM proteins. CHAPS was chosen for further optimization with benzonase and resulted in decellularized ECM that retained key proteins. This ECM was tested as both a 2D coating and a 3D intact tissue slice matrix for survival and maturation of embryonic stem cells. Only the 3D slices suggested maturation toward a pancreatic lineage. Therefore, this study created a 3D co-culture system to help further tissue engineering efforts.

Keywords: decellularization
extracellular matrix
pancreas
recellularization
stem cells
tissue engineering
Advisor: Rogers, Ian M
Three-dimensional Assembly and Characterization of Protein-based Tubular Constructs for Tissue Engineering

In this thesis I present a strategy for rolling highly aligned collagen sheets into tubular constructs which have applications as implantable bile duct grafts or in organ-on-a-chip systems. Aligned collagen sheets were extruded through a microfluidic device following a previously described protocol, and vertically stacked to achieve suitable mechanical properties for rolling. A rolling process was developed, characterized, and optimized for rolling tubular structures with a 700 μm inner diameter and 50 μm wall thickness, mimicking the dimensions of rat bile ducts. Rolled tubes were mechanically characterized for suture retention strength and burst pressure. The mechanism of failure in these tests was also investigated, providing insights for methods to further increase mechanical properties. Cholangiocyte precursors and cholangiocyte cysts were loaded into tubes in a custom-made tube hosting device and appeared to attach, spread, and remain viable up to 9 days in culture.

Keywords: Bile duct
Microfluidics
Tissue Engineering
Tubular constructs
Advisor: Guenther, Axel
Cyclical Variation in Predation Risk: Impacts on Snowshoe Hare (Lepus americanus) Offspring through Maternal Programming

Snowshoe hare (Lepus americanus) populations cycle over 10-year periods, primarily driven by predation. High predation risk triggers the decline phase of the cycle through both direct mortality and non-consumptive stress effects that curtail reproduction and survival. The decline phase is followed by an enigma, the prolonged low phase, where the population fails to recover. This suggests maternal stress effects may act to program offspring across generations in this population. Through a natural monitoring study spanning the hare cycle, we investigated the impact of changing predation risk and maternal stress on offspring. Offspring in the decline phase showed a suite of changes to their behaviour, condition, physiology and gene expression compared to offspring from the increase and peak phases, suggesting maternal programming is occurring. This study was novel in documenting changes in gene expression of hippocampal glucocorticoid receptors in response to a natural increase in predation risk in a wild mammal.

Keywords: Maternal effects
Non-consumptive effects
Population cycles
Predation
Snowshoe hare
Stress physiology
Advisor: Boonstra, Rudy
Three-phase Wireless Power Transfer for Electric Vehicle Charging with Improved Receiver Misalignment Tolerance

Charging of electric vehicles through inductive wireless power transfer (WPT) provides an attractive alternative to traditional wired charging. However, existing WPT systems display high degradation in efficiency and throughput power when transmitter and receiver become misaligned. A three-phase WPT system with magnetically decoupled transmitter windings is proposed to address this degradation. By optimal selection of the transmitter phase current distribution, a region of maximal flux density can be centred at the receiver location, achieving nearly constant efficiency and throughput power for receiver misalignment up to ±20cm. Excitation of the three-phase transmitter coil is provided by a conventional three-phase inverter, halving the number of semiconductors and gate drivers used with previous technologies. Experimental results demonstrate 92.97% coil efficiency and 88.45% system efficiency at perfect alignment at 3.3kW power transfer. Performance is shown to hardly degrade with misalignments up to 20cm, where coil efficiency remains at 90.52% and system efficiency at 86.66%.

Keywords: electric vehicle charging
receiver misalignment
wireless power transfer
Advisor: Lehn, Peter W
Characterizing the HLA Restriction and Functional Avidity of a HERV-specific T cell Receptor

Given that the rapid mutation of HIV mediates its immune escape, methods to enhance recognition of infected cells are urgently needed. Typically-dormant endogenous retrovirus (HERV) proteins are upregulated upon HIV infection and may thus serve as immutable surrogate markers of infected cells. In HIV patients, T cell responses to HERV epitopes correlate with an innate ability to control virus without therapy, raising the question of whether HERV-reactivity can enhance clearance of HIV-infected cells in an adoptive cell therapy approach. It remains to be seen whether de novo HERV-specificity can be conferred to allogeneic T cells by exogenous expression of HERV specific TCRs. Herein, we have expressed one-such TCR in a T cell line, showing that it successfully confers recognition of an epitope from HERV-K(HML-2)-Env. This in vitro system enabled an in-depth analysis of the TCR-peptide-MHC interaction, revealing that recognition is restricted to presentation by HLA B*07:02, and is enhanced by S-glutathionylation of the antigenic peptide.

Keywords: Adoptive cell therapy
Human Endogenous Retroviruses (HERV)
Human immunodeficiency virus (HIV)
Major histocompatibility complex (MHC)
S-glutathionylation
T cell receptor (TCR)
Advisor: Ostrowski, Mario A.
Zúñiga-Pflücker, Juan-Carlos
Hydrophilic Cargo-Loaded Microbubbles for Ultrasound-Triggered Local Delivery

Microbubbles are intravenous ultrasound-responsive agents that can cavitate upon insonation. There is ongoing interest in incorporating hydrophilic therapeutic and imaging agents into microbubbles for local, ultrasound-triggered delivery. A proof-of-concept microbubble capable of carrying hydrophilic molecules, providing ultrasound contrast, and cavitating was designed. Calcein was selected as a model cargo for optical verification of co-localization. First, 75% v/v Span 80 and 25% v/v Tween 80 surfactants were selected to solubilize calcein in cyclooctane. Second, calcein-loaded oil was emulsified as microdroplets stabilized with 2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-5000] phospholipids. Microdroplets were lyophilized, decafluorobutane gas-filled, and saline reconstituted to form calcein-loaded microbubbles. These were characterized for size distribution, calcein loading, contrast enhancement and cavitation. Calcein-loaded microbubbles (peak: 4.3 μm) demonstrated cargo co-localization and a concentration per microbubble volume of 0.077±0.038 mg/mL. Microbubbles provided ultrasound contrast and underwent inertial cavitation at MI≥0.77. This synthesis method may be extended to encapsulate other hydrophilic cargo in acoustically-active carriers.

Keywords: Drug Carrier
Localized Delivery
Ultrasound
Advisor: Matsuura, Naomi
Synthesis of a GlmU Bisubstrate Inhibitor

In an attempt to combat antibiotic resistance, new drugs are constantly being developed. One method of killing bacteria is to inhibit the formation of the cell wall, which is vital to the survival of the cell. This project involves the chemoenzymatic synthesis of a bisubstrate inhibitor of M. tuberculosis GlmU, as well as the synthesis of glucosamine-1-phosphate (GlcN-1-P), a commercially expensive substrate of GlmU. These two compounds were synthesized by making acetamides followed by phosphorylation using the enzyme NahK. Acetyltransferase kinetics and inhibition were assessed by using a continuous ultraviolet absorbance assay involving an Ellman’s reagent derivative and Michaelis-Menten kinetics. The bisubstrate inhibitor (EL44) inhibits GlmU competitively with respect to acetyl-CoA (AcCoA) with a Ki of 9 ± 2 μM, which makes it the strongest inhibitor among published M. tuberculosis GlmU inhibitors. It also noncompetitively inhibits GlmU with respect to GlcN-1-P with a Ki of 51 ± 6 μM. Overall, the two target compounds were successfully synthesized and the inhibitor exhibited inhibitory activity against the formation of N-acetylglucosamine-1-phosphate.

Keywords: Bisubstrate
GlmU
Glucosamine-1-phosphate
Inhibitor
Synthesis
Advisor: Nitz, Mark
Development, Characterization and Field Testing of a Passive Air Sampler for Monitoring Occupational Exposure to Mercury Vapors

An activated carbon-based passive air sampler for gaseous elemental mercury (GEM) was modified for personal exposure monitoring. Calibration yielded a sampling rate of 0.070 m3/day. Deployments lasting 8 hours result in method detection limits below the ASTDR and WHO minimum risk level of 200 ng/m3. The sampler has a measurement range of at least four orders of magnitude. Passive sampler derived air concentrations were not statistically significantly different from active air samplers, but passive sampling was more precise than personal pump sampling. Stationary and personal passive air samplers were used to characterize inhalation exposure to GEM of individuals (1) crushing mercury-containing compact fluorescent lights, (2) living and working in two Ghanaian artisanal and small-scale gold mining communities and (3) working at a Norwegian electronics recycling facility. Exposure concentrations ranging from

Keywords: Exposure estimates
Exposure monitoring
Gaseous elemental mercury
Passive sampling
Risk assessment
Advisor: Wania, Frank
Exploration of p-Block Adamantyl Chemistry

Adamantane, which is the simplest of the diamondoid molecules, shows great applicability in drug design, materials chemistry and as ligands for directed catalysts. Despite this, it has long been underrepresented in the field of organometallic chemistry. This underrepresentation can be traced back to the fact that stable, isolable, and anionic adamantyl sources have been difficult to synthesize. In 2017, the Fekl group developed diadamantyl zinc, which sought to address these problems with traditional anionic sources and has allowed for the synthesis of new metal adamantyl complexes. Building on this work, this project attempts to expand the adamantyl chemistry that can be accessed using diadamantyl zinc. The synthesis and partial characterization of 6 novel adamantyl compounds: tris-2-adamantyl bismuth (III), di-2-adamantyl Indium chloride, tri-2-adamantyl indium, di-2-adamantyl boron (III) bromide, di-2-adamantyl phosphorous bromide and tri-2-adamantyl are disclosed. Additionally, attempted synthesis of di-2-adamantyl ytterbium is discussed.

Keywords: Adamantane
Bismuth
Main Group
Organometalic
Reaction
Sodium
Advisor: Fekl, Ulrich
Investigating Pathways of Energy Transfer in Freshwater Food Webs

In complex ecological systems it is difficult to classify all interacting species, especially when the number of interacting organisms can be high, and species can respond differently to the same environment. Biochemical biotracers are useful tools to tease apart trends in food web structure through changing seasons. I used a novel biotracer and determined the presence of two highly branched isoprenoid (HBI) isomers in freshwater food webs of two temperate lakes. For the first time, my study demonstrated HBI trophic transfer from lower producers up to higher consumers. I then broadened these results by determining how fatty acid biotracers representative of three different energetic pathways change seasonally in top trophic position fish. Using and combining biotracer tools is important since lake ecosystems are facing multiple interacting stressors (e.g. eutrophication, climate change). The biotracers applied in my thesis helped provide a better understanding of the processes that shape food web structure.

Keywords: Biotracer
Fatty acids
Fish
Food web
Highly Branched Isoprenoids
Advisor: McMeans, Bailey