VictorJuiz/thesis huggingface dataset:
Investigation of Bioprocesses to Enhance Metal Extraction from Ores and Wastes in Mining Operations

Mine sites are a large source of genetic information that can be studied to explore ways of processing minerals using bacteria. This study investigates the bioleaching potential to extract nickel from ores and wastes at circumneutral pH and denitrifying conditions, and the cyanide biodegradation phenomenon at a gold heap leaching operation by examining naturally growing bacteria at two mine sites. Neutral pH bioleaching of nickel was achieved using nitrate as electron acceptor and oxidant. A mass balance revealed that about 20-30% of the original concentrate was leached over a period of more than 500 days. Faster rates could possibly be achieved by increasing biomass concentration. Thiobacillus was the dominant microbe identified in these microcosms. In gold heap leaching with cyanide, the microbial community was found to be almost entirely composed of a Hydrogenophaga with 16S sequence most similar to other alkaliphilic strains. This strain is presumably growing on the cyanide.

Advisor: Edwards, Elizabeth A
Novel Organic Photovoltaic Devices Using Chlorinated and Fluorinated Boron Subphthalocyanine Derivatives and Doctor Blade Coating Technique 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.

Keywords: Boron Subphthalocyanine
Doctor Blade Coating
Organic Photovoltaics
Six Sigma Optimization
Advisor: Bender, Timothy P
Dynamic Microtopography Arrays for Hybrid and Adaptive 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.

Keywords: Adaptive
Bio-inspiration
Hybrid
Reversible Adhesion
Soft Robotics
Switchable Adhesion
Advisor: Hatton, Benjamin D
Global Proteomics and Phosphoproteomics of Heart Failure Patients Elucidate Etiology-specific Signaling

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.

Keywords: cardiomyopathy
heart failure
myocardium
phosphoproteomics
proteomics
Advisor: Gramolini, Anthony O
Exploring Protein Interactions between CaV2 Calcium Channels and Pre-synaptic Scaffolding Proteins MINT and RIM in Invertebrates

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

Keywords: Evolution
Invertebrates
Protein Interactions
Synapse
Synaptic Transmission
Voltage-gated Calcium Channels
Advisor: Senatore, Adriano
Aerobic Fitness Level did not Modify Exercise Effects on Motor Skill Learning

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

Keywords: Aerobic exercise
Aerobic fitness level
High intensity interval training
Motor learning
Neuroplasticity
Peak oxygen uptake
Advisor: Chen, Joyce L
Parameter Estimation Methods for High Angle-of-attack Aerodynamic Modelling

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.

Keywords: Aerodynamics
Dynamic Modelling
Flight Simulation
Parameter Estimation
Stall
System Identification
Advisor: Grant, Peter R
Wireless Magnetically-actuated Dexterous Forceps Instruments for Neuroendoscopy

Robot-assisted minimally invasive surgical techniques offer improved instrument precision and dexterity, reduced patient trauma and risk, and lessens the skill gap among surgeons. These approaches are common in general surgery, urology, and gyenaecology. However, they remain largely absent for surgical applications with narrow, confined workspaces such as neuroendoscopy. This limitation stems from a lack of small yet dexterous robotic tools. To address this challenge, this research explores the development of a wireless, dexterous, magnetically-actuated forceps instrument for neuroendoscopic procedures whose goal is to improve intraventricular surgical reach. In this thesis, three magnetic designs were considered and characterized with respect to force and kinematic model accuracy. Furthermore, a custom magnetic system was built to evaluate the instruments’ performance during a pineal region tumour resection on a tumour analogue in a silicone brain phantom. This thesis concludes with a discussion on the performance on the devices and explores potential avenues for improvement.

Keywords: Forceps
Magnetic Actuation
Minimally Invasive Surgery
Neuroendoscopy
Surgical Robotics
Surgical Tool
Advisor: Drake, James
Diller, Eric
Effects of Cannabidiol and delta-9-Tetrahydrocannabinol in The Elevated Plus Maze and Forced Swim Tests

The effects of THC, CBD and a combination of CBD and THC (15:1) were tested in mice models of anxiety (elevated plus maze EPM) and depression (forced swim test FST). Adult, male CD1 mice were injected intraperitoneally (I.P.) with CBD (0-120mg/kg), THC (0-8mg/), CBD + THC (up to 120+8mg/kg), diazepam (0, 2.5mg/kg) or imipramine (0, 30mg/kg). EPM ran for 5mins, FST for 6mins, and open field test for 10mins. CBD was injected 30 or 60mins prior to testing and THC was injected 30mins prior. CBD decreased immobility time in FST. THC increased time spent in the open arms in EPM, and decreased immobility time in FST. The combination of CBD and THC was better than CBD or THC alone in FST at 30mins. CBD did not show anxiolytic effects but showed anti-depressant effects. THC had both anxiolytic and antidepressant effects at some doses. CBD and THC combined might be useful in patients with anxiety and depression.

Keywords: cannabidiol
cannabis
elevated plus maze
forced swim test
mice
tetrahydrocannabinol
Advisor: Burnham, W M
The Longitudinal Relationships between Biomarkers of Alzheimer’s Disease

Despite well-described temporal staging, the relationships between Alzheimer’s disease (AD) biomarkers remain unclear. First, using cross-lagged panel models, we examined the reciprocal longitudinal influences between biomarkers of amyloid-beta (Aβ) and phospho-tau (p-tau), hallmark proteins that accumulate in the AD brain, in both asymptomatic/presymptomatic elderly (HC), and in subjects with AD or mild cognitive impairment (AD/MCI) over 48 months. Second, reciprocal relationships between brain Aβ deposition and white matter hyperintensity volumes (WMH), presumed to be of vascular origin, were examined. In HC, cerebrospinal fluid (CSF) Aβ changes led to increased Aβ deposition and increased CSF p-tau concentrations, and CSF p-tau exacerbated Aβ deposition. In contrast, in AD/MCI, CSF p-tau exacerbated Aβ deposition, but p-tau progressed independently of Aβ biomarkers. WMH led to Aβ deposition in HC, while in MCI, it was Aβ deposition that predicted incident WMH. Processes underlying CSF Aβ changes, and cerebrovascular disease, may initiate the amyloid cascade in presymptomatic stages.

Keywords: Alzheimer's disease
Biomarkers
Advisor: Swardfager, Walter
Black, Sandra E
High-dose Vtamin D Supplementation, Adiposity, and Serum Lipids in Early Childhood

Background: Observational research has suggested a relationship between lower vitamin D status and higher adiposity in children. No randomized clinical trials have evaluated this relationship. Methods: This was a secondary analysis of a double-blind randomized clinical trial. Linear regression adjusted for baseline was used to determine the effect of wintertime high-dose (2000 IU/day) vs. standard-dose (400 IU/day) vitamin D supplementation on end of winter adiposity and cardiovascular risk in healthy children aged 1-5 years. Results: 545 children were included in the analysis (n = 275, 50.5% in the 2000 IU/day group). There was no clinically meaningful difference between standard vs. high-dose vitamin D supplementation on BMI z-score or serum lipids. However, children who received high-dose vitamin D had a lower waist circumference z-score than those receiving standard-dose supplementation. Conclusion: High-dose vitamin D supplementation may have a role in minimizing wintertime adiposity gains in preschool children, but further research is needed.

Keywords: Adiposity
Early Childhood
Serum Lipids
Vitamin D
Waist Circumference
zBMI
Advisor: Maguire, Jonathon L
Antiseizure Effects of Cannabinoids in the Amygdala Kindling Model

Focal Impaired Awareness Seizures (FIAS) are the most common seizures in adults and are typically drug resistant. Amygdala-kindling is a pre-clinical model of FIAS with secondary generalization. The present study was designed to assess the effectiveness and safety of cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), and a combination of CBD and THC (15:1) in suppressing generalized and focal kindled seizures. CBD alone suppressed both generalized seizures and focal seizures at sub-toxic doses. THC alone also suppressed generalized and focal seizures, but only at doses that produced psychotoxic effects. The addition of a low dose of THC to CBD (15:1) left-shifted the dose- response curve for CBD, producing lower ED50s for both generalized and focal seizures. No toxicity was seen with this combination. CBD and THC both have anti-seizure properties. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC may be useful in the clinical management of FIAS.

Keywords: Amygdala
Brain
Cannabinoid
Epilepsy
Kindling
Seizure
Advisor: Burnham, Willets M
Adult Neurogenesis in Naked Mole-Rats: Time Course of Cell Maturation and The Effects of Social Novelty

Naked mole-rats (NMR) are one of the only eusocial mammalian species. Their complex social structure makes them unique for the study of interactions between adult neurogenesis and social behavior. I explored the time course of maturation of newly born cells in neurogenic regions of the adult NMR brain. I found that most new NMR cells mature by 5 months. To test whether cell proliferation is related to processing social cues, I examined the effects of a novel social stimulus in two subordinate subcastes. Soldiers produced more new cells in the subventricular zone than workers. NMRs exposed to a novel social stimulus were more aggressive and investigated their counterpart more than those in a familiar pair. Soldiers in novel pairs, but not workers, spent more time sniffing the genitals of their counterpart. Thus, caste and social context play a role in the rate of proliferation and the behavior of NMRs.

Keywords: naked mole-rat
neurogenesis
social behavior
Advisor: Holmes, Melissa M
Regulation of Glucagon-like Peptide-1 Secretion by the Exocytotic Protein Munc18-1

The incretin glucagon-like peptide-1 (GLP-1) is a rhythmically secreted insulin-secretion enhancing hormone produced in the intestinal L-cell. The increasing incidence of Type 2 Diabetes warrants the advent of new therapies that can increase endogenous GLP-1 secretion, which will manipulate regulatory L-cell secretory pathways such as exocytosis. Three exocytotic proteins have already been identified as regulators of GLP-1 secretion. I hypothesized that the accessory exocytotic protein, Munc18-1, is also an important regulator of GLP-1 secretion in the L-cell - specifically at the peak of its secretion. Munc18-1 expression in many, but not all L-cells was confirmed, and its recruitment to the cell membrane was observed under stimulation. The role of Munc18-1 in GLP-1 secretion was established by loss-of-function experiments in the Munc18-1 knockdown mGLUTag L-cell line, inducible L-cell Munc18-1 knockout mice and primary Munc18-1 knockout L-cells. Together, the results indicate that Munc18-1 is an essential regulator of peak GLP-1 secretion.

Keywords: enteroendocrine
exocytosis
GLP-1
Munc18-1
SNARE
Stxbp1
Advisor: Brubaker, Patricia L
Management of Idiopathic Pulmonary Fibrosis: A Survey of Canadian Respirologists

Objective: To characterize the treatment of idiopathic pulmonary fibrosis (IPF) by Canadian respirologists. Methods: We performed a cross-sectional survey of Canadian respirologist who are either Canadian Thoracic Society members or attended the 2018 Canadian Respiratory Conference. Results: Sixty-three respirologists participated (response rate 29%). Substantial variability in the application of guideline recommendations was seen with respect to both acute and chronic management strategies for IPF. Physicians were least confident in their recommendations for antacid use, antifibrotic treatment strategies, and corticosteroid use in IPF exacerbations. Most physicians believe placebo-controlled trials of corticosteroids for IPF exacerbations are needed (92%) and ethical (83%). Physician characteristics are associated with particular practice patterns. Practicing in a transplant centre and involvement in clinical trials were most often associated with specific management strategies. Conclusions: Canadian respirologists report diverse practices regarding IPF treatment. This survey provides insight into the variability of treatment strategies and may guide future trial design.

Keywords: Candian
Idiopathic pulmonary fibrosis
Management
Survey
Advisor: Stanbrook, Matthew B
Proteomics of Prostate Proximal Fluids to Guide Biomarker Discovery

Prostate Cancer is the most common non-skin cancer in men. Current diagnostic factors are inaccurate in predicting outcome, resulting in over- and undertreatment of many men. Improved prognostic factors that enable non-invasive diagnosis and follow-up are strongly needed. I hypothesize that comparative proteomic profiling of a direct EPS cohort will identify prognostic biomarkers. I developed and applied a shotgun proteomics assay to a cohort of 148 clinically stratified direct EPS samples. These analyses identified 1271 peptides that are significant between risk categories. Results were independently verified in a direct EPS cohort from Virginia with 115 samples (59 overlap). 228 of 1271 peptides showed the same trend over risk groups in both datasets. Putative biomarkers will be validated using targeted proteomics assays in an independent cohort of post-DRE urines. In the future these assays could assist to accurately stratifying patients into prostate cancer risk groups.

Advisor: Kislinger, Thomas
Interactions between EGF and the IGF-1 Receptor in Mediating hGly2-GLP-2-induced Proliferation in the Murine Small Intestine

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic hormone that promotes intestinal proliferation through downstream mediators. Two known mediators are insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF), both essential for the proliferative effect of GLP-2. I hypothesized that pre- and/or co-EGF enhances IGF-1-mediated GLP-2-induced proliferation in the murine model. Chronic combination treatment of EGF and GLP-2 increased intestinal growth in C57Bl/6 mice compared to vehicle, GLP-2 and respective EGF treatments. Treatment of pre-EGF+co-EGF+GLP-2 in intestinal epithelial IGF-1 receptor (IGF-1R) knockout mice restored intestinal growth despite the lack of a receptor essential for GLP-2 signaling. Finally, IGF-1 treatment in organoids did not have an additive effect to EGF on proliferation, but managed to replace EGF as an essential growth factor in the media to maintain normal proliferation. Together, these data suggest that exogenous EGF is an essential mediator for GLP-2 that can supersede the missing signaling pathway of IGF-1R.

Keywords: EGF
Endocrine
GLP-2
Growth Hormones
IGF-1
Intestine
Advisor: Brubaker, Patricia L
Bio-printing of Mesenchymal Stem Cells for Skin Reconstruction after Burns

Skin regeneration is crucial in burns due to severe damage of the protective barrier. Mesenchy-mal Stem Cells (MSC), with their regenerative properties, are essential for wound repair. We have invented and validated a novel intraoperatively usable hand-held bio-printer, which depos-its MSCs directly on the wounds. We conducted a full-thickness porcine burn study and determined skin regeneration following the deposition of umbilical cord mesenchymal stromal cells with this novel surgical device and examined wound healing at day 28 histologically. Our data demonstrated a significant enhancement in wound healing with similar epidermal re-generation when compared to healthy skin, as well as a significant increase in collagen for-mation, enhanced neovascularization, and less scar and contracture formation compared to con-trols. Here, we showed the safety and efficacy of this novel bio-printer, thus demonstrating its poten-tial as a flexible, surgical device and as an alternative solution for the treatment of burn wounds.

Keywords: Bio-Printing
Burns
Mesenchymal Stem Cells
Skin Regeneration
Tissue Engineering
Wound Healing
Advisor: Jeschke, PhD, Dr. Marc G.
The Effects of Western-diet, Palmitate, and TNFα on Hypothalamic Circadian Rhythms, NPY Expression, Neuroinflammation, and Cellular Insulin Sensitivity

Western diets are typically high in saturated fats and sugar and thus induce weight gain, alter circadian rhythms, increase inflammatory cytokines, and alter whole body glucose homeostasis. However, the links between circadian and hypothalamic energy homeostasis remain undefined. In C57BL/6-J mice, the Western diet significantly decreased peak food consumption, with a concomitant decrease in hypothalamic expression of orexigenic neuropeptides. In vitro, palmitate induced neuropeptide Y (Npy) and Bmal1, and reduced Per2 expression in a BMAL1-dependent manner. TNFα, a palmitate-induced cytokine, activated neuroinflammatory cytokine expression and reduced insulin sensitivity in NPY-expressing neurons. Cellular neuroinflammation occurred through the canonical IKK-β/NF-κB pathway. The induction of insulin resistance by TNFα was maintained after with IKK-β/NF-κB pathway inhibition, indicating that TNFα-mediated neuroinflammation and insulin resistance occurs via distinct mechanisms. With this study, I provide insight into the mechanistic link between fatty acid-induced feeding-related neuropeptide dysregulation, inflammatory activation, circadian rhythms, and insulin resistance.

Keywords: circadian rhythms
endocrinology
feeding
hypothalamus
inflammation
insulin resistance
Advisor: Belsham, Denise D
Brubaker, Patricia L