VictorJuiz/thesis huggingface dataset:
The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell

Neural stem cells (NSCs) in the adult forebrain are thought to comprise a subpopulation of cells that express glial fibrillary acidic protein (GFAP), termed B cells. These GFAP+ cells generate proliferating neuroblasts that migrate from the lateral ventricle subependyma along the rostral migratory stream to become olfactory bulb interneurons. Based on this lineage, we set out to create a NSC deficient mouse through targeted ablation of dividing GFAP+ cells in vivo. We successfully depleted the GFAP+ cells as seen using an in vitro colony forming assay in multiple kill paradigms, however we were unable to permanently eliminate the multipotent, self-renewing colony forming cells. Instead, the targeted ablation of GFAP+ cells revealed an upstream, GFAP- cell that was induced to proliferate in the presence of leukemia inhibitory factor (LIF). These findings support the hypothesis that a population of GFAP-, LIF responsive cells are the definitive adult NSC upstream of GFAP+ cells.

Keywords: Adult neural stem cells
Neuroscience
Neural stem cells
Advisor: Morshead, Cindi M.
Development of Monolithically Integrated Photonic Devices Through Simulation and Characterization

Simulations were carried out to determine the optical properties of 2 different layer structures which have been used in quantum well intermixed devices. The supported modes, effective refractive indices and optimal device dimensions prior to intermixing were reported. 1.5 micrometer ridge waveguides with 600 micrometer bend radii are shown to be suitable for minimizing loss. A first approximation to the intermixed structures were also simulated. An Asymmetric Mach-Zehnder Interferometer (AMZI) fabricated using a sputtered SiO2 Quantum Well Intermixing (QWI) process was also characterized. A 100 GHz channel spacing with an extinction ratio up to 16 dB was observed. Tuning of the device was achieved using current injection. A 0.45 nm tuning range was achieved at 15 mA of injected current. The design of a monolithically integrated all optical binary half-adder is also presented, with physical dimensions based on the results of the previous simulations.

Keywords: Monolithical Integration
Photonics
Advisor: Aitchison, J. Stewart
DNA Palindrome Revision in Mammalian Cells

A DNA palindrome is a sequence of DNA followed by an exact inverted copy of itself. Palindromes are associated with gross chromosomal instability in mammalian cells. This may be related to their ability to extrude a double-stranded cruciform structure. In mammalian cells, palindromes have been shown to undergo centre-directed rearrangements resulting in a central region of asymmetry. This process occurs via a mechanism termed 'centre break palindrome revision'. In this thesis, I have investigated palindrome revision in mammalian cells using two existing assays. In the first, performed by transfection of an extrachromosomal palindromic dimer, I have shown that joining of palindrome-mediated double-strand breaks does not depend solely on NHEJ and instead relies heavily on an alternate end-joining pathway. Using the second assay, the Line78 mouse model which contains a 15.4kb transgenic palindrome, I have shown that small modifications near the centre of the palindrome prevent these centre-directed rearrangements possibly by inhibiting cruciform formation.

Keywords: DNA Repair
Palindrome
Advisor: Lewis, Susanna
Intrinsic Artefacts of Circular Cone-beam Computed Tomography

Circular source and detector trajectories in cone-beam computed tomography (CT) are known to collect insufficient data for accurate object reconstruction. One model predicts that the lacking information corresponds to a shift-variant cone of missing spatial frequency components in the local Fourier domain. These predictions were experimentally verified by imaging small, localized objects and observing their Fourier transforms. Measurements indicated that the internal angle of the ‘missing cone’ varies as the angle of locally intersecting x rays with respect to the horizontal plane, as expected. Object recovery was also found to depend greatly on the distribution of the object’s frequency spectrum relative to the missing cone, as predicted. Findings agreed with more anatomically relevant phantoms, which showed preferential intensity discrepancies at gradients oriented within or near the missing cone. Methods for artefact correction are in general limited to approximation unless a priori information is incorporated.

Keywords: cone-beam
computed tomography
artefacts
artifacts
Defrise
circular
Fourier
Advisor: Jaffray, David A.
Mitochondrial Remodeling During Hyperosmotic Stress

Hyperosmotic stress represents a major threat to cellular integrity and may lead to cell death via apoptosis. Accordingly, each cell reacts to hyperosmolarity with a set of functional and structural compensatory responses. Recently it has been shown that the mitochondria remodel during hyperosmotic stress. Although changes in mitochondrial dynamics could be crucial for both adaptation and apoptosis, hyperosmolarity-induced mitochondrial remodeling has not been characterized. We found that hyperosmotic stress translocates dynamin like protein 1 (DLP-1) to the mitochondria and induces DLP-1 mediated, F-actin-modulated, Rac-dependent fragmentation of these organelles in LLC-PK1 cells. Downregulation of DLP-1 mitigates the activation of the osmotic response element and increases the susceptibility of tubular cells to hyperosmotically-induced apoptosis, suggesting that DLP-1 (or mitochondrial fragmentation) may have a protective role during osmotic stress. The hyperosmolarity-triggered remodeling of the mitochondrion represents a hitherto unrecognized response to osmotic shock, which may have significant impact on adaptation and apoptosis.

Keywords: Hyperosmotic stress
mitochondria
Advisor: Kapus, Andras
Measurement and Modeling of Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs) in the Indoor Environment

The indoor environment is a potentially dominant source of exposure for polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). This thesis describes a study on levels, sources, emissions, and fate of PBDEs and PCBs indoors. PBDEs and PCBs air levels in 20 indoor environments in Toronto were sampled and measured. The geometric means of PBDE (Σ10BDE) and PCB (Σ35PCB) concentrations were 0.072 and 7.2 ng m-3 respectively. Statistical analysis on chemical profiles distinguished the chemical sources in the 20 environments. A multimedia indoor environmental model was applied on two test rooms. Estimated PBDE and PCB emission rates were 5.4-550 ng h-1 and 280-5870 ng h-1 respectively. Particle movement dominates within-room transport processes, and dust removal and air advection are the main chemical loss processes. Temperature, particle concentration and deposition velocity, and air exchange rate are the most influential parameters, which can alter source or sink behaviors of household products for the chemicals.

Keywords: PBDEs
PCBs
Indoor Environment
Modeling
Measurement
Advisor: Diamond, Miriam L.
Application of Bayesian Inference Techniques for Calibrating Eutrophication Models

This research aims to integrate mathematical water quality models with Bayesian inference techniques for obtaining effective model calibration and rigorous assessment of the uncertainty underlying model predictions. The first part of my work combines a Bayesian calibration framework with a complex biogeochemical model to reproduce oligo-, meso- and eutrophic lake conditions. The model accurately describes the observed patterns and also provides realistic estimates of predictive uncertainty for water quality variables. The Bayesian estimations are also used for appraising the exceedance frequency and confidence of compliance of different water quality criteria. The second part introduces a Bayesian hierarchical framework (BHF) for calibrating eutrophication models at multiple systems (or sites of the same system). The models calibrated under the BHF provided accurate system representations for all the scenarios examined. The BHF allows overcoming problems of insufficient local data by “borrowing strength” from well-studied sites. Both frameworks can facilitate environmental management decisions.

Keywords: Bayesian Calibration
Eutrophication
Aquatic Biogeochemical Models
Markov Chain Monte Carlo
Hierarchical Bayes
Uncertainty Analysis
Water Quality Standards
Environmental Management
Advisor: Arhonditsis, George
Pretreatment of Pulp Mill Wastewater Treatment Residues to Improve Their Anaerobic Digestion

Anaerobic digestion of excess biological wastewater treatment sludge (WAS) from pulp mills has the potential to reduce disposal costs and to generate energy through biogas production. The organic matter in WAS is highly structured, which normally hinders biogas production. This study investigated three methods of pretreating WAS from two different pulp mills before anaerobic digestion to improve biogas yield and production rate. The three pretreatment methods tested were: i) thermal pretreatment at 170oC, ii) caustic pretreatment at 140oC and pH 12, and iii) sonication at 20 kHz and 1 W/mL. Thermal pretreatment proved to be the most effective, increasing biogas yield by 280% and 50% and increasing production rates 300-fold and 10-fold for the two samples, respectively. Caustic pretreatment showed similar results, but resulted in the formation of soluble non-biodegradable compounds. Sonication was the least effective pretreatment and did not substantially increase biogas yield, but increased biogas production rate.

Keywords: anaerobic digestion
sludge
wastewater treatment
pretreatment
pulp mill
waste activated sludge
Advisor: Master, Emma
Tran, Honghi
Design and Evaluation of a Disulphide-crosslinked Hyaluronan Hydrogel for Regeneration of the Intervertebral Disc

A cysteine-containing elastin-like polypeptide (ELP2cys) was successfully synthesized and purified, and was shown to behave in a similar fashion to other well-characterized ELPs. Incorporating the ELP2cys as a crosslinking agent into a solution of sulphated hyaluronan (CMHA-S) not only decreased the gelation time of the solution but also increased the crosslinking density of the resultant hydrogel, in turn increasing both the resiliency and stiffness of the construct. Preliminary in vitro work involved culture of human disc cells, followed by their encapsulation within the hydrogel. Unfortunately the results were inconclusive, although it appeared as though the addition of ELP2cys to the matrix did not negatively affect the viability of the cells, as compared to hydrogels with CMHA-S only. This study showed that ELP2cys is a valuable addition to the family of recombinant elastin-like polypeptides, and shows promise as a crosslinking agent in the formation of hyaluronan hydrogels.

Keywords: hyaluronan hydrogel
elastin-like polypeptide
nucleus pulposus
regeneration
mechanical response
coacervation
0541
Advisor: Woodhouse, Kimberly A.
The Influence of Elliptical Nozzle Holes on Mixing and Combustion in Direct Injection Natural Gas Engines

Experiments were conducted to compare mixing and combustion of natural gas jets from round and elliptical nozzle holes in an optically accessible combustion bomb. A flame ionization detector was used to measure the concentration fields of the two jet types. Pressure data, combustion imaging, and hydrocarbon measurements of exhaust gas were used to compare the ignition delay, heat release, and combustion efficiency of the two nozzles. Concentration measurements indicated that the elliptical nozzle produced jets with smaller rich core regions and lower peak concentrations at all conditions. Firing tests indicated that the two nozzles produced equivalent ignition delays. Peak heat release rates were higher for the round nozzle, while the elliptical nozzle produced smoother transitions from premixed to diffusion burning. Combustion efficiency was slightly higher for the round nozzle. Results indicate that elliptical nozzles could potentially lower NOx and particulate emissions, but further experiments are required to test this hypothesis.

Keywords: natural gas
alternative fuel
mechanical engineering
internal combustion engines
Advisor: Wallace, James S.
Application of Singular Spectrum-based Change-point Analysis to EMG Event Detection

Electromyogram (EMG) is an established tool to study operation of neuromuscular systems. In analysing EMG signals, accurate detection of the movement-related events in the signal is frequently necessary. I explored the application of change-point detection algorithm proposed by Moskvina et. al., 2003 to EMG event detection, and evaluated the technique’s performance comparing it to two common threshold-based event detection methods and to the visual estimates of the EMG events performed by trained practitioners in the field. The algorithm was implemented in MATLAB and applied to EMG segments recorded from wrist and trunk muscles. The quality and frequency of successful detection were assessed for all methods, using the average visual estimate as the baseline, against which techniques were evaluated. The application showed that the change-point detection can successfully locate multiple changes in the EMG signal, but the maximum value of the detection statistic did not always identify the muscle activation onset.

Keywords: EMG signal processing
change-point detection
singular spectrum analysis-based detection
Advisor: Popovic, Milos R.
Improvement of Passivity of Fe - xCr Alloys (x < 10%) by Cycling Through the Reactivation Potential

Classically 13% Cr is required for stable passivity of steel in acidic and neutral solutions. Some authors (Mansfeld, Fujimoto) have published potential cycling procedures that generate thick Cr-rich films. Fujimoto cycles right to the transpassivity potential and back in H2SO4 solution. Our idea is to work close to the reactivation potential where the passive film (Fe2O3) is reductively dissolved to Fe2+. While using an equimolar acetate buffer (pH 4.7), we have obtained new insights into the reactivation process. It is under a kind of thermodynamic control, in that the film cannot be reduced, and the metal cannot be dissolved, faster than would exceed the equilibrium concentration of Fe2+ at the electrode surface. Reductive dissolution leads to gel-like Cr-rich film, but Fe dissolution occurs through it, if formed in a single step. However alternating formation and reductive dissolution of a Fe-rich film assist the formation of a more robust Cr-rich film

Keywords: Fe - Cr
Low-Cr alloys
Potential cycling
Advisor: Newman, Roger C.
Functional Characterization of Members of a Clade of F-box Proteins in Arabidopsis thaliana

In Arabidopsis, the F-box gene family encodes a large number of proteins postulated to act as substrate selectors for proteasome-mediated protein degradation. Recent reports document the importance of F-box proteins in developmental and metabolic signaling. Our microarray analyses of inflorescences of the brevipedicellus(bp) mutant indicate several F-box proteins are upregulated, suggesting that BP represses these genes in wild type plants to condition normal inflorescence development. We undertook analyses to examine the function of these proteins and their contribution to the pleiotropic phenotypes of bp. Yeast-2-hybrid screens revealed that the F-box protein At1g80440 binds to phenylalanine ammonia lyase-1(PAL1), the gateway enzyme of phenylpropanoid metabolism. Transgenic lines driven by the 35S cauliflower mosaic virus were attained but could not be propagated, suggesting a fatal phenotype. BP driven F-box expression results in phyllotaxy defects, manifest as alterations in the emergence of inflorescence and floral meristems in the axils of some cauline leaves.

Keywords: F-box Proteins
Arabidopsis thaliana
brevipedicellus
yeast two hybrid
Advisor: Riggs, C. Daniel
Progressive Validity Metamodel Trust Region Optimization

The goal of this work was to develop metamodels of the MDO framework piMDO and provide new research in metamodeling strategies. The theory of existing metamodels is presented and implementation details are given. A new trust region scheme --- metamodel trust region optimization (MTRO) --- was developed. This method uses a progressive level of minimum validity in order to reduce the number of sample points required for the optimization process. Higher levels of validity require denser point distributions, but the reducing size of the region during the optimization process mitigates an increase the number of points required. New metamodeling strategies include: inherited optimal latin hypercube sampling, hybrid latin hypercube sampling, and kriging with BFGS. MTRO performs better than traditional trust region methods for single discipline problems and is competitive against other MDO architectures when used with a CSSO algorithm. Advanced metamodeling methods proved to be inefficient in trust region methods.

Keywords: Multidisciplinary Optimization
Metamodels
Response Surfaces
Surrogate Models
Trust Region Optimization
Progressive Validity
Leave-k-out Cross-Validation
Concurrent Subspace Optimization
Advisor: Martins, Joaquim R. R. A.
An Empirical Approach to Understanding the Relationship Between Recombination and Fitness

The persistence of sex is a recurrent conundrum in evolutionary biology because sex is costly. These costs may be accounted for by looking at the outcome of sex, namely that sex causes genetic mixing. Recombination is one of the processes by which sex causes genetic mixing; determining when recombination is advantageous may alleviate some of the costs of sex. The advantages of recombination are in the effects of recombination and the influences thereupon. The first experiment focuses on the effects of recombination on the mean fitness and variance in fitness. A second experiment examines the influences on recombination by addressing whether recombination is a general response to poor condition. Specifically, the impact on recombination rate of genotypes with variable fitness is investigated. Differing fitness effects are not correlated to recombination rates. Conversely, coincidence, a recombination related trait, is positively correlated with fitness.

Keywords: fitness
recombination
coincidence
Drosophila melanogaster
evolution of sex
Advisor: Agrawal, Aneil
Labeling and Detection of Marrow Derived Mesenchymal Stromal Cells using Magnetic Resonance Imaging

Stem cell therapies hold great promise for diseases such as stroke, where few effective treatment options exist. Clinical translation of experimental stem cell therapies requires the ability to monitor delivery and behaviour of cells non-invasively in-vivo with clinical imaging modalities such as MRI. This thesis presents the translation of established methods for labelling and imaging stem cells with specialized MRI systems to a more clinically relevant setting. A methodology for harvesting and labelling a cell population containing stem cells with iron oxide for detection with a clinical MRI system is presented and single cell detection is demonstrated in-vitro. The feasibility of detecting iron oxide labelled stem cells intravenously delivered in a rat model of stroke is tested. Results demonstrate that while MRI is highly sensitive to the presence and distribution of iron oxide containing cells in-vivo the true origin of these cells remains ambiguous with the current methodology.

Keywords: MRI
MPIO
stem cells
superparamagnetic iron oxide
stroke
Advisor: Mikulis, David J.
Stanisz, Greg
The Processes of Care after Colorectal Cancer Surgery in Ontario

Colorectal cancer (CRC) is common in Ontario. This study described the processes of care following CRC resection, and identified CRC relapse from administrative data. Methods: CRC patients aged 18-80 from 1996-2001 with a colorectal resection were identified from the Ontario Cancer Registry. Linked discharge abstracts and physician billings were examined for physician visits, body imaging and endoscopy over the 5 year follow-up period. Administrative codes suggesting disease relapse were compared with patient charts. Results: Overall, 12,804 patients were identified and 8,804 had no evidence of relapse. Most (96.2%) patients had general practitioner follow-up, while 49.3% had medical oncology and 80.4% had general surgery follow-up. Greater than 90% of patients received endoscopy, while only 68.7% of patients received body imaging. Detecting disease relapse was 87.5% sensitive and 93.0% specific. Conclusions: There is potential for improving post-resectional follow-up in CRC patients. It is possible to detect relapse through administrative databases.

Keywords: colorectal cancer
surveillance
relapse
Advisor: Law, Calvin
Hodgson, David
A Climate Change Impact Assessment on the Spread of Furunculosis in the Ouje-Bougoumou Region

A climate change impact assessment was conducted to examine the spread of furunculosis found in the fish species of Ouje-Bougoumou; and subsequently to examine the resulting impacts on the health of the community. A past assessment was performed to assess whether there was a temporal relationship between increased temperatures and past incidences of furunculosis using observed climate data and traditional ecological knowledge (TEK) data. To project future impacts of climate change, climate models, lake models and TEK were used. Findings show that the rise in air mean temperature coincides with the timeline of past incidences of furunculosis. It is predicted that the lake temperatures will remain suitable for the presence of A. salmonicida; thus, it is likely that the disease will persist throughout the twenty-first century. To conclude, climate change is not eliminated as a plausible factor to the onset of furunculosis.

Keywords: climate change
Aboriginal health
furunculosis
Advisor: Gough, William A.
The Role of Carbonic Anhydrase in the Modulation of Central Respiratory-related pH/CO2 Chemoreceptor-stimulated Breathing in the Leopard Frog (Rana pipiens) Following Chronic Hypoxia and Chronic Hypercapnia

The aim of this thesis was to elucidate the role of carbonic anhydrase (CA) in the modulation of central pH/CO2-sensitive fictive breathing (measured using in vitro brainstem-spinal cord preparations) in leopard frogs (Rana pipiens) following exposure to chronic hypercapnia (CHC) and chronic hypoxia (CH). CHC caused an augmentation in fictive breathing compared to the controls (normoxic normocapnic). Addition of acetazolamide (ACTZ), a cell-permeant CA inhibitor, to the superfusate reduced fictive breathing in the controls and abolished the CHC-induced augmentation of fictive breathing. ACTZ had no effect on preparations taken from frogs exposed to CH. Addition of bovine CA to the superfusate did not alter fictive breathing in any group, suggesting that the effects of ACTZ were due to inhibition of intracellular CA. Taken together, these results indicate that CA is involved in central pH/CO2 chemoreception and the CHC-induced increase in fictive breathing in the leopard frog.

Keywords: Acetazolamide
Amphibian Respiration
Carbonic Anhydrase
Central pH/CO2 Chemoreceptors
Chronic Hypercapnia
Chronic Hypoxia
Fictive Breathing
In Vitro Brainstem-Spinal Cord Preparation
Leopard Frogs
Advisor: Reid, Stephen G.