VictorJuiz/thesis huggingface dataset:
Characterization of the Microtubule Organizing Centres in Osteoclasts
Keywords: Bone
Centrosome
Golgi
Microtubule
MTOC
Osteoclast

Osteoclasts are highly specialized, multinucleated cells responsible for the selective resorption of bone matrix during bone remodeling and the pathological bone destruction found in osteoporosis. Our study investigated the origin of microtubules during osteoclast differentiation and bone resorption. Microtubule nucleation is generally restricted to specific subcellular sites called microtubule organizing centres (MTOCs) and is primarily fulfilled by the centrosome in metazoan cells. While mononuclear osteoclast precursor cells contain centrosomal MTOCs, previous research has suggested that functional centrosomal MTOCs do not exist in multinucleated osteoclasts. Through live-cell imaging, immunofluorescence, and ultrastructural analyses, we observed that most, if not all centrosomes donated from precursor cells remained individually functional and clustered early during osteoclastogenesis. Furthermore, by visualizing Golgi reorganization and Golgi-derived microtubules, we identified the Golgi as a possible non-centrosomal MTOC that potentially facilitates polarized microtubule arrays in osteoclasts. Together these findings show that multinucleated osteoclasts employ unique centrosomal and non-centrosomal MTOCs to organize microtubules.
Risk Factors for Alzheimer’s Disease and Cortical Thickness in a Population-Based Sample of Middle-Aged Men and Women
Keywords: Alzheimer's disease
Cortical Thickness
Risk Factors

Alzheimer’s Disease (AD) is a neurodegenerative disorder with a decades-long preclinical phase. Preclinical stages of AD are associated with cortical thinning. Female sex and age, as well as several genetic and modifiable metabolic factors increase risk for AD. Therefore, here I examined, in a population-based sample of younger (
Protein Capture on Multiwavelength SERS Substrates: A Study on Width-Graded Plasmonic Gratings and Cytochrome C
Keywords: biosensor
cytochrome c
electron beam lithography
multiwavelength
self-assembling monolayer
surface enhanced Raman spectroscopy

Multiwavelength width-graded nano-gratings have been shown to localize high electric fields and thus are strong surface-enhanced-Raman-spectroscopy (SERS) substrate candidates for disease detection. The 2D geometry of graded gratings, however, produce a small sensing volume. Moreover, the bare silver (Ag) surfaces exhibit a positive charge in aqueous environments which impedes the accumulation of positively-charged analytes at the SERS hotspots of the grating surface. In this thesis, we demonstrate the efficacy of Ag surface functionalization to overcome both issues using cytochrome c (Cc) as a model biomolecule. By preparing self-assembling monolayers (SAMs) of 16-mercaptohexadecanoic acid (MHDA) on Ag, we achieved SERS detection of Cc at 1μM. Further, the MDHA SAM allows for immobilization of Cc onto the Ag surface for detection in dry phase, an approach that produced stronger Raman signals compared to those from solution phase. We conclude with promising generalization of our approach to detection of other biomolecules of interest.
Classifying Schizophrenia Based on Response to Antipsychotic Medications
Keywords: Clozapine
Outcomes
Predictors
Psychosis
Response
Schizophrenia

Clozapine is the main treatment for patients with significant psychotic symptoms despite adequate trials of non-clozapine antipsychotics. However, 40-70% of patients show suboptimal response to clozapine. We aimed to: (1) examine the relationship between delay in initiating clozapine and treatment outcomes through a literature review; (2) examine clozapine response/non-response trajectories and predictors of long-term non-response through a retrospective chart review; and (3) determine the relationships between glutamatergic neurometabolites and cortical thickness through a cross-sectional imaging study. Delay in initiating clozapine and number of hospitalizations were associated with poor clozapine response. Further, response trajectories ranged from sustained response or non-response to developed response or non-response. Finally, glutamatergic neurometabolite levels in the dorsal anterior cingulate cortex were associated with cortical thinning in the right prefrontal cortex in patients with treatment-resistant schizophrenia, independent of age, sex, treatment, and illness severity. This work advances our understanding of treatment-resistant schizophrenia from clinical and neuropathological perspectives.
Transforming Existing Stateful Network Protocol Applications into Effective Protocol-Specific Security Testing Tools
Keywords: Protocols
Security
Testing
Vulnerabilities

To discover low-level security vulnerabilities in target applications that implement stateful network protocols, security researchers usually employ manually-constructed protocol-specific testing tools. Due to the complexity and heterogeneity of network protocols, however, building such tools for every network protocol used by target programs is a challenging task. We propose a semi-automated technique for creating protocol-specific testing tools, which leverages an existing application that implements a network protocol (a source), and converts it into a testing tool that can be used for bug discovery in any target program that “speaks” the same protocol. We call our implementation of this method InSource, and, by measuring coverage gain, show that InSource can test a target just as well a manually-created protocol- specific testing tool. Furthermore, we show that InSource is effective at testing applications that use different protocols, as long as a source application for each protocol is available.
The Impact of the Repeal of the 2015 Health Physical Education Curriculum on Ontario Teachers
Keywords: Comprehensive Sexuality Education
Doug Ford
Health Physical Education
Ontario
Sex Education
Sexuality Education

This project analyzes how the repeal of the 2015 Health Physical Education curriculum for Grades 1-8 impacted Ontario teachers. Eight Grades 7-12 teachers from one school board in southern Ontario were interviewed. Interviews found that participants faced major constraints in teaching sex education, both before and after the repeal. All participants disagreed with the repeal of the 2015 curriculum and felt the 2018 interim curriculum did not meet the needs of students. Both elementary and secondary teachers expressed concern over teaching sexual health topics over the 2018-2019 school year due to the political tension surrounding sex education. Teachers who felt supported by their school administration felt more comfortable teaching sex education over the 2018-2019 school year than those who lacked administrative support. This study emphasizes the chaos surrounding sex education following the 2018 Ontario election, the danger of relying on outdated curriculum, and the importance of comprehensive sexuality education.
Identification and Characterization of T Cell-inflamed vs non-T Cell-inflamed Tumours based on Chemokine Expression Reveals Distinct Immunophenotypes in Primary and Metastatic Tumours in Pancreatic Cancer
Keywords: Bioinformatics
Chemokines
Immunology
Metastases
Pancreatic Cancer
T lymphocytes

Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all solid tumours. Despite progress in other cancers, immunotherapy remains ineffective against this malignancy. This is, in part, due to a paucity of CD8+ T cells in most pancreatic cancer tumours. Here, we investigate the role of chemokines in CD8+ T cell infiltration in PDAC. Analysis of 79 primary resections uncovered a panel of chemokines associated with infiltration, consisting of CCL4, CCL5, CXCL9, and CXCL10. Segregating 113 resections based on expression of this panel, those with higher expression had increased immune activation signatures; including MHC I presentation, dendritic cell (DC) activation, and Batf3-driven DC presence, with no differences in mutational nor neoantigen load. Results were consistent across three independent cohorts, including 107 liver metastases, suggesting conserved immunobiology between primary and metastatic sites. Taken together, these results suggest a potential role for these chemokines in CD8+ T cell recruitment in PDAC.
Investigating the Roles and Regulation of Testis-specific eIF4Es during Drosophila Spermatogenesis
Keywords: Drosophila
eIF4E
gene expression
spermatogenesis
translational control
translation initiation

Translational regulation is an important mechanism for controlling gene expression, and is associated with maintaining cellular homeostasis and regulating aspects of development. Eukaryotic initiation factor 4Es (eIF4Es) are mRNA cap-binding proteins required for the initiation of translation. Although most eukaryotic genomes encode several paralogs of eIF4E, their roles and regulation remain largely uncharacterized. Drosophila melanogaster has eight paralogs and four of them are enriched in the testis (eIF4E-3, -4, -5 and -7). These paralogs are expressed at distinct stages of spermatogenesis, suggesting they have differential roles. Further characterization of eIF4E-5 demonstrated that it is involved in polarization and individualization of spermatids, likely via localized translation of aPKC and Soti. In addition, eIF4E-5 works in the same pathway as Orb2 to regulate these cellular processes. Overall, my results suggest that the Drosophila male germline serves as an excellent model to examine mechanisms regulating eIF4Es in translation initiation.
Novel Industrial Scale Radio Frequency Inductively Coupled Plasma Torch
Keywords: computational fluid dynamics
heat transfer
industrial
nanoparticle synthesis
powder spheroidization
radio frequency inductively coupled plasma

A novel industrial scale radio frequency inductively coupled plasma (RF-ICP) torch design is proposed which uses a conical geometry. The objective of this thesis is to investigate whether this geometry can provide reduced gas power consumption and a higher quantity of spheroidized (i.e., melted) particles. The investigation is conducted using computational fluid dynamic simulations in ANSYS Fluent by simulating the injection of powder particles into the plasma discharge produced by the RF-ICP torch. Simulations are performed to optimize the conical torch and compare its performance to a conventional RF-ICP torch. It is found that the new conical torch achieves spheroidization ratios up to 2 times higher than the conventional torch, due to higher temperatures and an induction zone closer to particles. Additionally, it runs at 42% lower gas consumption and can achieve industrially acceptable spheroidization ratios at half the power level of the conventional torch.
Receipt of Overactive Bladder Drugs and Incident Dementia: a Population-based Case-control Study
Keywords: Adrenergic beta-3 Receptor Agonists
Case-Control Studies
Dementia
Muscarinic Antagonists
Urinary Bladder
Overactive
Urological Agents

Second-line treatment for overactive bladder (OAB), consists of muscarinic antagonists or β-3 agonists. There is limited knowledge about the differential risk of incident dementia associated with receiving the various OAB drugs available. We conducted a population-based case-control study, where cases with incident dementia were age- and sex-matched to controls from the general population. We performed multivariate conditional logistic regression to estimate the odds of incident dementia associated with receiving individual OAB antimuscarinics, relative to a β-3 agonist, mirabegron. Patients had an increased odds of incident dementia associated with receiving antimuscarinic drugs, solifenacin (OR 1.24; 95% CI 1.08-1.43) and darifenacin (OR 1.30; 95% CI 1.08-1.56), compared to those receiving mirabegron, in the six months prior to diagnosis. In the six months to one year prior to diagnosis, receipt of any OAB antimuscarinic was associated with increased odds of incident dementia (OR 1.29; 95% CI 1.09-1.54), compared to receipt of mirabegron.
Examining the Efficacy and Mechanism of a Peptide Modified Hydrogel for Wound Healing Applications
Keywords: Biomaterials
Hydrogel
Immune-modulating
QHREDGS
Wound Healing

Wound healing is a pandemic, challenging doctors, patient quality of life, and healthcare dollars. Current research is focused on developing a multi-modal approach which seeks to heal wounds during all phases of healing, as opposed to tackling one. Using the QHREDGS (Q- peptide)-hydrogel, we seek to elucidate the mechanistic effect of the Q-Peptide on the immune system, specifically evaluating macrophage polarization and how this may affect scar formation. When cultured in the presence of the Q-Peptide, bone marrow derived macrophages differentiated into a novel polarization that is favourable in promoting wound healing. Further, in a clinically relevant model of healthy human healing, the Q-Peptide accelerated and attenuated scarring. This research suggests that the Q-Peptide hydrogel supports wound healing by enacting a response on all phases of healing, adding motivation driving the clinical translation of this biomaterial.
Immuno-mass Spectrometric Identification of Predictive Biomarkers of Response and/or Toxicity to Immune Checkpoint Inhibitors
Keywords: Biomarkers
Immunotherapy
Mass Spectrometry

Immune checkpoint inhibitors (ICIs) are humanized antibodies that target specific inhibitory molecules, such as programmed cell death protein 1 (PD-1) and its ligand, PD-L1. The limitations of ICIs are high cost, limited response rate and development of immune-related adverse events (irAEs). Predictive and monitoring biomarkers of ICIs are an unmet need. We hypothesized that patients who develop irAEs will produce specific autoantibodies indicative of an autoimmune-like response. We developed a novel methodology that involves immunoaffinity purification of serum autoantibodies, incubation with target autoantigens and mass spectrometric identification of autoantibody targets. Using our methodology and electrochemiluminescence immunoassay for validation, we found that patients treated with pembrolizumab have anti-thyroglobulin antibody titers that are significantly associated with irAE development. Furthermore, we identified several potential autoantibody targets in a patient with ICI-induced myocarditis. Predictive biomarkers of ICIs will save significant resources, ensure proper patient selection for treatment, and spare certain patients from irAEs.
End-to-end Network Slicing for Flash Crowds in Multi-region Cloud Platform
Keywords: 5G
End-to-end network slicing
Flash crowds
Management and Orchestration
Network Function Virtualization
Software Defined Networking

End-to-end network slicing is an auspicious paradigm, which promises to lead the way towards efficiently addressing the problems of legacy networks. Based on softwarization and virtualization, it is capable of enabling network as a service (NaaS) and allow the coexistence of multiple networks on the same physical infrastructure. These features make network slicing suitable for mission-critical scenarios, including flash crowds and emergency situations, and foster the required system performance. In this thesis, we design and implement an end-to-end network slicing platform aiming to deploy agile, flexible and scalable network architecture. We provide insights into the emergency scenarios and elaborate on the system requirements that it needs to fulfill. In order to evaluate the performance of NaaS, we implement a wireless testbed featuring fully virtualized systems, and conduct a series of experiments. We present evaluations to validate the proposed slicing model and demonstrate its applicability for flash crowds.
Novel Organic Photovoltaic Devices Using Chlorinated and Fluorinated Boron Subphthalocyanine Derivatives and Doctor Blade Coating Technique Optimization
Keywords: Boron Subphthalocyanine
Doctor Blade Coating
Organic Photovoltaics
Six Sigma Optimization

This thesis explored new materials and methods for the fabrication and performance optimization of organic photovoltaic (OPV) devices. Chlorinated and fluorinated derivatives of boron subphthalocyanine (BsubPc) electron acceptors were combined with an α-sexithiophene electron donor, and structure-property relationships were characterized for optimal OPV performance. Despite overwhelming similarities in material properties, the axially fluorinated BsubPc derivative (F-BsubPc) resulted in a significantly lower (50%) power conversion efficiency (PCE) compared to its chlorinated counterpart (Cl-BsubPc). However, mixtures of Cl-BsubPc and F-BsubPc have yielded greatly improved PCE trends compared to F-BsubPc films alone. This thesis also focused on the blade coating solution deposition technique to transition towards commercially viable OPV fabrication. Considering the complex and multivariant nature of blade coating, process optimization was completed using Six Sigma methodologies. Combination of solution processed and thermally evaporated layers into one OPV device was also investigated for increased OPV absorbance.
Dynamic Microtopography Arrays for Hybrid and Adaptive Switchable Adhesion
Keywords: Adaptive
Bio-inspiration
Hybrid
Reversible Adhesion
Soft Robotics
Switchable Adhesion

The feet of many insects contain both a ‘sticky’ pad and sharp claws that can be intelligently actuated to ‘switch’ (on/off) their adhesion to smooth and rough surfaces, respectively. In contrast, synthetic switchable adhesives designs are mechanistically simple and unable to adapt to real-world surfaces. This work proposes a bio-inspired hybrid (multi-mechanistic) and adaptive device that can control adhesion and friction on both smooth and rough surfaces. A novel pneumatic smart surface is designed that both actuates (rotates) multifunctional adhesive microtopography and provides sensory feedback at multiple independent areas on the surface. It will be shown that by rotating topography, the surface can switch between sticky and non-sticky states (99.3% reduction) and can also interlock with holes and protrusions (asperities) of rough surfaces. Through integrated and external sensory feedback combined local control, the device can sense adhesion loss, surface contact, and ultimately develop localized adhesive strategies that optimise global adhesion.
Global Proteomics and Phosphoproteomics of Heart Failure Patients Elucidate Etiology-specific Signaling
Keywords: cardiomyopathy
heart failure
myocardium
phosphoproteomics
proteomics

The prognosis and treatment outcomes of heart failure patients rely on patient etiology yet the underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major form of protein regulation, profoundly altering signaling networks. Here, we identified disease-specific regulation of signaling pathways between dilated (DCM) and ischemic (ICM) cardiomyopathies as well as regional differences within infarcted hearts. Myocardial tissues were explanted from DCM patients, infarct, peri-, and non-infarct regions of ICM patients, and non-failing controls (NFC). Following phosphorylated peptide enrichment, peptide fractions were subjected to liquid chromatography-tandem mass spectrometry for global proteomic and phosphoproteomics profiling. Differential protein and pathway analyses were performed to determine protein expression, phosphorylation, and pathways that were significantly altered in pair-wise comparisons (DCM vs. NFC, infarct vs. non-infarct, and peri- vs. non-infarct). This comprehensive study presents novel findings on disease-specific regulation of molecular pathways in heart failure to reveal suitable targets for therapeutic interventions.
Exploring Protein Interactions between CaV2 Calcium Channels and Pre-synaptic Scaffolding Proteins MINT and RIM in Invertebrates
Keywords: Evolution
Invertebrates
Protein Interactions
Synapse
Synaptic Transmission
Voltage-gated Calcium Channels

During synaptic transmission, voltage-gated calcium type-2 (CaV2) channels mediate transient influxes of Ca2+ into the cytoplasm. This event activates synaptic vesicle (SV) calcium sensors, which facilitates docking, priming and fusion at the plasma membrane, and the subsequent release of SV contents into the synaptic cleft. A direct interaction has been proposed to tether CaV2 channels and SVs in nanometer proximity, primarily mediated by scaffolding proteins that bind to the distal C-terminus of CaV2 at a conserved PDZ-ligand domain. Here, we explored interactions between CaV2 and the scaffolding proteins RIM and MINT in vitro in the arthropod Drosophila melanogaster and the cnidarian Nematostella vectensis to understand the evolution of the synapse through conservation of CaV2 channel protein structure- function. We found that interactions between these proteins are conserved and occur at similar domains and ligand domains, which suggest that the CaV2-MINT and CaV2-RIM interactions serve as important evolutionary adaptations for the emergence of synapses
Aerobic Fitness Level did not Modify Exercise Effects on Motor Skill Learning
Keywords: Aerobic exercise
Aerobic fitness level
High intensity interval training
Motor learning
Neuroplasticity
Peak oxygen uptake

Aerobic exercise enhances motor skill learning. However, studies have focused on highly aerobically trained individuals. It is unknown if less aerobically trained individuals can also benefit from exercise for motor skill learning. We investigated how aerobic fitness level (Aerobically Untrained (AU) versus Aerobically Trained (AT)) affects an individual’s ability to learn a motor skill after exercise. We hypothesized that AU would have worse motor skill retention than AT after Exercise, but not Rest (control). Participants practiced a visuomotor tracking task, cycled (Exercise) or sat (Rest) for 25-minutes, and completed a 24-hour motor skill retention test. Mean VO2peak (ml/kg/min) for AU-Exercise (n=12) = 31.6±4.2, AU-Rest (n=12) = 31.2±3.8, AT-Exercise (n=10) = 51.5±7.2, AT-Rest (n=10) = 52.7±7.6. All groups improved motor skill performance during acquisition [F(3.15, 126.21)=258.71, p
Parameter Estimation Methods for High Angle-of-attack Aerodynamic Modelling
Keywords: Aerodynamics
Dynamic Modelling
Flight Simulation
Parameter Estimation
Stall
System Identification

In recent years, extensive research has been performed in post-stall aerodynamic model development to facilitate the use of simulator-based stall recovery training for commercial pilots. To develop these aerodynamic models, the parameters within a postulated model structure are often estimated from flight test data in a process referred to as aircraft parameter estimation. However, the complex dynamics involved in stall poses some notable challenges to the parameter estimation procedure. This thesis presents and investigates a variety of parameter estimation methods that yield more accurate estimates than traditional techniques when applied to stall modelling problems. Specifically, these methods look to reduce parameter biases that occur during post-stall modelling problems due to the presence of large model deficiencies. The presented methods are applied to both simulated and real aircraft flight data to demonstrate the improvements seen over traditional aircraft parameter estimation methods.