VictorJuiz/thesis huggingface dataset:
Modulation of TGF‐β Receptor 1 signalling in Live Cells

TGF-β negatively affects the maintenance and expansion of hematopoietic stem cells ex vivo and its inhibition has been widely studied as a treatment for numerous hematopoietic disorders and cancers. Current inhibitory strategies (small molecule ATP competitors and neutralizing antibodies) are compared to a novel cell-permeable peptide-based inhibitor of TGF-β RI. Multiple levels of assay from biochemical to functional are utilized with the aim of applying the most successful inhibitor to hematopoietic stem cell culture. The neutralizing antibody proved ineffective in the short-term biochemical assay but was extremely effective at neutralizing TGF-β signalling in proliferation and hematopoietic colony-forming cell assays with no evidence of toxicity. The small molecule inhibitors (SD-208 and Pyrazole TGF-β RI inhibitor) were equally effective at micromolar levels in all forms of assay, with SD-208 being slightly more potent. The novel peptide inhibitor proved ineffective in all assays, which is likely a result of its rapid degradation in live cells.

Keywords: TGF-β Inhibition
Peptide
ATP competitive inhibitor
neutralzing antibody
Advisor: Audet, Julie
An In Vitro Model System For Cardiac Cell Therapy

Embryonic stem cells (ESC) constitute a promising source of cells for cardiac transplantation strategies. However, complexities associated with in vivo studies have made it difficult to develop a thorough understanding of cell integration. We have engineered an in vitro system that recapitulates the native cardiac environment using 300μm thick collagen scaffolds seeded with neonatal cardiomyocytes (CM) and electrical field stimulation. The injection of undifferentiated ESC served as a baseline to assess the validity of studying cell transplantation in this model. Yfp-ESC survived and proliferated over several days in model tissue. ESC were not observed to significantly differentiate into the cardiac lineage, and did not integrate with the cardiac cell population. While the injection of ESC improved cardiac cell number, tissue functional properties were hindered. The methods developed herein can be readily adapted to study ESC derived progenitor and differentiated cells, to elucidate the optimal cell state for ESC-mediated cell therapy.

Keywords: Cardiac Tissue Engineering
Embryonic Stem Cells
Cell Therapy
In Vitro Model
Advisor: Radisic, Milica
Encouraging Energy Conservation Through Information Display: A New Approach

Much study is required on how human behaviour affects resource consumption. Not only are Human Factors Engineers well equipped to study how to shape human behaviour, but contributors to conservation literature have asked for their involvement in the domain of energy conservation. This study took a novel, systematic, human-factors approach to providing feedback on energy consumption by testing the effects of providing three levels of feedback on conservation performance. The results showed that providing physical, functional, and task-based information aided performance more than physical information alone, but no more than providing physical and functional information together. More research is required to determine if physical and task information alone could achieve the same result, if study results would differ when two opposing task goals were given, and if the varying levels of feedback have a greater effect on novices.

Keywords: behaviour
behavior
feedback
conservation
information
display
energy
consumption
systematic
human
factors
engineering
Advisor: Jamieson, Gregory Allan
The Effects of Population Density and Knock-downs of Llipid Metabolism Genes on the Expression of Cuticular Hydrocarbons in Drosophila melanogaser

In Drosophila melanogaster, chemical cues in the form of cuticular hydrocarbons play an important role in reproductive behavior. The social and genetic processes that regulate their expression, however, are poorly understood. The social environment has been shown to influence hydrocarbon display. In this study, the effect of population density on the expression of hydrocarbons was evaluated. I demonstrate that the production of certain hydrocarbons depends on the population density in which the animal is reared. Individual hydrocarbons fluctuate in quantity independently from one another but the peaks during a light-dark cycle are static depending mostly on chain length. The regulation of fly hydrocarbons which are density-dependent is shown to be sexually dimorphic. The RNAi knockdown of various putative lipid metabolism genes was also used to study hydrocarbon expression. This study reveals that lipid metabolism genes which are not obvious mediators of HC synthesis influence cuticular hydrocarbon profiles.

Keywords: hydrocarbons
Drosophila melanogaster
pheromone
population density
Advisor: Levine, Joel
Spacecraft Thermal Design Optimization

Spacecraft thermal design is an inverse problem that requires one to determine the choice of surface properties that yield a desired temperature distribution within a satellite. The current techniques for spacecraft thermal design are very much in the frame of trial and error. The goal of this work is to move away from that procedure, and have the thermal design solely dependent on heat transfer parameters. It will be shown that the only relevant parameters to attain this are ones which pertain to radiation. In particular, these parameters are absorptivity and emissivity. We intend to utilize an optimal/analytical approach, and obtain a solution via optimization. As mentioned in the motivation, having a purely passive thermal system will greatly reduce costs, and our optimization solution will enable that. This topic involves heat transfer (conduction and radiation), spacecraft thermal network models, numerical optimization, and materials selection.

Keywords: Spacecraft Design
Thermal Optimization
0756
Advisor: Damaren, Christopher John
A Study of Soot Cake Formation in a Diesel Particulate Filter

A methodology was developed to dissect diesel particulate filters to study the time effect of loading for two different fuels: ULSD and a biodiesel blend. Filters loaded with soot from a diesel engine for exposure times of 1, 2, 5 and 10 hours were fractured and samples of filter substrates were analyzed using Raman spectroscopy and scanning electron microscopy. Observations revealed the sharp rise in pressure drop to be attributable to the clogging of the pores in the channel wall, leading to the formation of a pore-bridge. Cross sectional imaging of wall sections revealed this pore-bridge to be shallow, with significant particulate depositions limited to the first quarter of the depth of the filter walls. Images revealed increasingly dense deposits and the formation of coarse particles and soot cakes. Raman spectroscopy revealed no significant graphitization of the soot cake. The dissection methodology exhibits significant potential for future studies on DPFs.

Keywords: Diesel Emissions
Diesel Particulate Filter
Advisor: Wallace, James S.
Towards a Microfluidics-based Nucleic Acid Biosensor Using Immobilized Quantum Dot – DNA Conjugates for FRET Detection of Target Oligonucleotides

The potential for an electrokinetically driven, FRET-based microfluidic biosensor for SNP discrimination has been explored. The method functionalized the glass wall of a PDMS/glass microfluidics channel with multidentate thiol ligands to noncovalently immobilize MPA capped CdSe/ZnS QDs. Single stranded probe DNA could then be immobilized to QDs and target material could be delivered electrokinetically to the sensing surface. SNP discrimination could then occur by manipulation of shear, electrical and thermal effects derived from the applied voltage. The stability of immobilized QDs was investigated by EOF experiments that applied 500 V and 100 V voltages for 10 minutes to initiate electrokintetic flow. Fluorescence intensity measurements showed nearly complete removal of QDs from slides when compared with controls at both voltages. Pressure driven flow experiments demonstrated reduced dissociation of immobilized of QDs compared to channels exposed to EOF. A covalent approach is likely necessary to ensure stability of immobilized QDs during EOF.

Keywords: Analytical
Chemistry
Advisor: Krull, Ulrich Jorg
Long-range Rover Localization by Matching Lidar Scans to Orbital Elevation Maps

Current planetary rover localization techniques are lacking in autonomy and accuracy. An autonomous method of globally localizing a rover is proposed by matching features extractedvfrom a 3D orbital elevation map and rover-based 3D lidar scans. Localization can be further improved by including odometry measurements as well as orientation measurements from an inclinometer and sun sensor. The methodology was tested with real data from a Mars-Moon analogue site on Devon Island, Nunavut. By tying 23 real scans together with simulated odometry over a 10km traverse, the algorithm was able to localize with varying degrees of accuracy. Output uncertainties were large due to large input uncertainties, but these could be reduced in future experimentation by minimizing the use of simulated input data. It was concluded that the architecture could be used to accurately and autonomously localize a rover over long-range traverses.

Keywords: localization
mobile robotics
autonomy
space robotics
Advisor: Barfoot, Timothy D.
Peptide Modification of Sodium Alginate To Induce Selective Capture of Cardiac Cell Populations

Isolation of selected populations from heterogeneous cell mixtures and retrieval of the captured population of interest for regenerative medicine and diagnostics applications is one of the challenges that may be addressed by microfluidics. An affinity adhesion strategy was tested using the tetrapeptides RGDS (arg-gly-asp-ser), REDV (arg-glu-asp-val) and VAPG (val-ala-pro-gly) to modify an alginate hydrogel surface layer to selectively adhere fibroblast (FB), endothelial (EC) and smooth muscle cell (SMC) populations, respectively, of the non-myocyte cardiac cell fraction. Incorporation of peptides into sodium alginate gel surface coatings demonstrated a preferential, seeding density-dependent adhesion relationship on alginate-RGDS when tested with a cardiomyocyte-depleted cell suspension in both static culture and in microfluidic devices. Seeding density-dependent attachment was seen with close to 100% release of viable cells from coated surfaces upon application of ethylenediaminetetraacetic acid (EDTA). Further work will optimize the system with REDV and VAPG to capture ECs and SMCs.

Keywords: alginate
cardiac
RGDS
adhesion
VAPG
REDV
microfluidics
Advisor: Radisic, Milica
HMG-CoA Reductase Inhibition Reduces T-cell Activation, TNFα Production, and MMP-9 Gene Expression in a Superantigen-mediated Mouse Model of Kawasaki Disease

Kawasaki disease (KD) is a multisystem vasculitis leading to coronary artery aneurysm formation. In a superantigen-mediated murine model of KD, the development of coronary arteritis is mediated by T-cells through the production of TNFα. TNFα localizes to the coronary arteries, where it induces the expression of MMP-9, resulting in the breakdown of elastin and the formation of aneurysms. Statins have been recently shown to have anti-inflammatory and immunomodulatory properties as a result of the inhibition of small GTPases. In our murine model of KD, atorvastatin treatment inhibits superantigen mediated T- cell proliferation and cytokine production, including IL-2 and TNFα. Additionally, statin treatment inhibits TNFα-mediated MMP-9 production by vascular smooth muscle cells, through inhibition of the MEK/ERK pathway. Thus, statins modulate each of the critical steps in the pathogenesis of KD in a disease model, suggesting that statin use could alter the outcome and prognosis of children suffering with this disease.

Keywords: Kawasaki Disease
Statins
Advisor: Ito, Shinya
Yeung, Rae S. M.
A Diffusion Tensor Imaging Investigation of White Matter in Pediatric Multiple Sclerosis Patients

Background: To explore normal-appearing white matter (NAWM) in pediatric-onset multiple sclerosis (MS) patients, using diffusion tensor imaging (DTI). DTI study provides measures of WM integrity in adult MS patients. Pediatric MS patients provide a uniquely early window for exploring pathological components of myelin disruption. Methods: DTI data were obtained for 23 pediatric MS patients and 17 healthy children. Images were acquired using GE LX1.5T scanner (DTI parameters: 25 directions, 5mm slice thickness, b=1000s/mm2). Fractional anisotropy (FA) and apparent diffusion co-efficient (ADC) were analyzed in lesions and NAWM throughout corpus callosum (CC) and hemispheres. Results: Altered NAWM integrity in MS patients relative to controls is demonstrated by: reduced FA values (p<0.0001) and elevated ADC values (p<0.05) throughout CC and hemispheres. Conclusions: DTI measures show widespread disruption of WM integrity in children with MS extending beyond visible lesions. These findings implicate diffuse and potentially very early WM degeneration in MS pathobiology.

Keywords: Multiple Sclerosis
Diffusion Tensor Imaging
Pediatric
MRI
Advisor: Banwell, Brenda
A 1Mbps 0.18μm CMOS Soft-output Decoder for Product Turbo Codes

A product turbo code (PTC) decoder application specific integrated circuit (ASIC) is designed in 0.18μm 1P6M CMOS with embedded SRAM. From simulation, an operating frequency of 73.1 MHz at typical conditions is obtained, yielding a throughput of 3.8 Mbps with 4 decoding iterations, while consuming 103.4 mW. The total area is 5.13 mm2. Assuming the ASIC would be used as a hard macro, the area could be reduced to 1.7 mm2. The ASIC was tested at 20 MHz under typical conditions, which resulted in a throughput of 1.0 Mbps at 1.8V supply while consuming 36.6 mW. By making a slight modification, this design can be easily scaled to support IEEE 802.16d WiMAX. Allow for this, and moving to a 45nm process an estimated throughput of 9.44 Mbps with 4 iterations can be obtained. Total macro area would be approximately 0.11 mm2.

Keywords: error correcting code
ECC
product turbo decoder
vlsi
hamming code
Advisor: Gulak, P. Glenn
Adolescent Compliance with Oral Hygiene Instructions during Fixed Orthodontic Treatment: A Pilot Study

Objectives: To determine compliance with oral hygiene instructions (OHI) of adolescents receiving two-arch fixed orthodontic treatment in a graduate orthodontic clinic and to identify predictive factors. Methods: Forty-one patients in a longitudinal pilot study were provided standardized OHI and assessed at baseline: before bonding (T1); 30 days after (T2), and 150 days after bonding (T3). Oral hygiene was measured using plaque and gingival indices. Compliance predictors were identified from questionnaires and patient records. Results: Good compliers increased from 10 at T1 to 29 at T3. Univariate analyses found perceived severity of malocclusion, school performance and parental marital status to be significant predictors. Multiple logistic regression identified having married parents and good school performance as significant predictors. Conclusions: In the sample studied, after initially worsening, compliance with OHI improved at five months after bonding. Adolescents with married parents and those reporting good academic performance in school were more likely to comply.

Keywords: Orthodontics
Compliance
Advisor: Suri, Sunjay
Developmental Regulation of the type-A Gamma-Aminobutyric Acid Receptor (GABA-AR) Signaling in the Fetal Rat Lung

The fetal lung epithelium secretes fluid into the potential pulmonary air-spaces by actively transporting chloride (Cl¯) into the lung lumen. This Cl¯-driven fluid secretion declines with the progression of lung development. Recent studies demonstrate that the A-type γ-aminobutyric acid receptor (GABAAR), a Cl¯ channel, and glutamic acid decarboxylase (GAD65/67), key GABA-synthesizing enzymes, are expressed in adult pulmonary epithelial cells (ECs), forming an autocrine GABAAR signaling system. My thesis study revealed that GABAAR π- and β2- subunits are expressed in high levels in the fetal rat lung epithelium and decline at birth, consistent with pattern of fluid secretion. Immunohistochemistry showed distinct profiles of expression for GABAAR subunits and GAD65/67. Treatment of alveolar ECs with dexamethasone reduced the GABAAR π-subunit expression. These results suggest that the GABAAR signaling in the fetal pulmonary epithelium is developmentally regulated and the GABAAR expression and GABAAR-mediated Cl¯ secretion in pulmonary ECs may be regulated by glucosteroids.

Keywords: Lung Development
Type-A Gamma Aminobutyric Acid Receptor (GABA-AR) and Glutamic Acid Decarboxylase (GAD) in Fetal Lungs
Fluid Secretion in the Mammalian Lungs
Cell and Molecular Biology
Advisor: Lu, Wei-Yang
Is Depression Associated with Edentulism in Canadian Adults?

It has been hypothesized that depression can be both a risk factor and a consequence of oral diseases. Tooth loss leads to discomfort, pain, and functional limitations which could lead to disability and, subsequently, to handicap. However, the association between depression and edentulism has not been established yet. Data from the Canadian Community Health Survey (CCHS) Cycle 2.1 were used to examine the association between edentulism and depression in community-dwelling Canadians 45 years of age and older. Separate logistic regression models were developed for dentate and edentulous groups as well. Different regression selection methods were implemented and the area under the ROC curve was used to select models with the highest predictability. Analysis showed that edentulism was not associated with depression. For the edentulous group, oral/facial pain was the only oral health factor predicting depression, whereas avoiding smiling or laughing, dry mouth, oral/facial pain predicted depression in the dentate individuals.

Keywords: edentulism
depression
older adults
Advisor: Lawrence, Herenia P.
2 2D Model of Semi-molten Drop Impact for Thermal Spray Application

In thermal spraying, semi-molten (or partially-melted) particles are likely to form when the sprayed particles are insufficiently heated, or when a composite material is deposited. The present 2D model serves to begin to assess the spreading behavior of a semi-molten particle when impacting a solid substrate. An Immersed-Boundary (IB) scheme was implemented in an axisymmetric fluid model to simulate fluid flow in the presence of a solid core. The IB method calculates a forcing term, which is added to the momentum equation, to enforce the no-slip boundary condition at the core surface. Results are presented for the impact of a semi-molten tin droplet of radius R for a wide range of solid core radii r, varying the drop size ratio r/R, and the impact velocity Uo.

Keywords: thermal spray
model
semi-molten particle
IB and VOF method
Advisor: Mostaghimi, Javad
Bussmann, Markus
Ectopic Notch Activation in Developing Podocytes Impairs Slit Diaphragm Formation and Induces Abnormal Podocyte Differentiation

Podocytes are terminally differentiated epithelial cells which regulate glomerular permselectivity by their cell-cell junctions, known as slit diaphragms (SD). Notch signaling regulates podocyte cell fate specification and downregulation of Notch targets occurs with terminal podocyte differentiation. The effects of constitutive Notch activation in developing podocytes on podocyte differentiation and function were determined using a podocyte-specific Cre-lox-p(Neph/Cre) approach. Proteinuria was noted shortly after birth denoting loss of glomerular permselectivity in transgenic mice (CRE;NIC mice). Histologic and molecular analyses of CRE;NIC-expressing mice at onset of proteinuria, show morphologic and cellular changes in podocytes including de-differentiation, proliferation and de novo expression of Pax2. Prior to onset of proteinuria, lower protein levels of key SD proteins are observed while SD mRNA expression is preserved in CRE;NIC mice. Consequently, constitutive Notch signaling in developing podocytes opposes terminal differentiation with deleterious consequences on SD assembly and thereafter, glomerular permselectivity.

Keywords: Notch
glomerulosclerosis
Advisor: Piscione, Tino D.
Rosenblum, Norman D.
Synthesis of Highly Functionalized Tetrahydroisoquinolines by a Palladium-catalyzed Domino ortho-Alkylation/Heck Reaction Sequence and Diastereoselective Aryne Diels-Alder Reactions

We report a palladium-catalyzed, norbornene mediated synthesis of tetrahydroisoquinolines via a domino ortho-alkylation/Heck reaction sequence. The desired products are obtained in moderate to excellent yields starting from readily available aryl iodides. The reaction conditions can be extended to the formation of tetrahydroisoquinolinones and tetrahydrobenzo[c]azepines. The reaction allows for sequential intermolecular and intramolecular ortho-alkylations. However, the product yields are higher with ortho-blocked aryl iodides, which simplify the domino process to one intramolecular ortho-alkylation and a Heck reaction. The Lautens group has previously reported diastereoselective aryne Diels-Alder reactions of benzyne with dienes supporting a chiral auxiliary at its terminal carbon. In an effort to extend this work and allow access to a wider variety of 1,4-dihydronaphthalenes, we attempted the synthesis of dienes supporting a chiral auxiliary at a central carbon. Chiral pyridyne precursors were also synthesized, in an attempt to vary the source of chirality in diastereoselective cycloadditions.

Keywords: Chemistry
Organic Chemistry
Catalysis
Palladium
Aryne
Benzyne
Diels-Alder
Advisor: Lautens, Mark
Closed Loop Control of the Ankle Joint Using Functional Electrical Stimulation

The restoration of arm-free standing in paraplegic individuals can be accomplished with the help of functional electrical stimulation (FES). The key component of such a system is a controller that can modulate FES induced muscle contractions in real-time, such that artificially produced forces in the legs and abdominal muscles are able to generate stable standing posture. A 57 year-old individual with chronic ASIA-A (American Spinal Injury Association), T3/4 level spinal cord injury (SCI) participated in this study. The objective was to determine if a proportional-derivative (PD) or proportional-integral-derivative (PID) controller could be used to regulate FES induced muscle contractions in the ankle joint to allow it to maintain balance of the entire body during quiet standing, while exhibiting physiological dynamics seen in able-bodied individuals while doing so.

Keywords: Closed Loop Control
Functional Electrical Stimulation
Ankle Joint
Inverted Pendulum
Advisor: Popovic, Milos R.
The Benthic Invertebrate Community of Lakes Previously Impaired by MiningI-related Acidification Near Wawa, Ontario

Iron mining began in Wawa, Ontario in the late 1800s and ceased in 1998. The sintering process of iron pyrite produced sulfur dioxide which led to the acidification of nearby lakes. Benthic macroinvertebrate samples were collected from lakes along a gradient of historical impairment in Wawa to examine the extent to which the benthos of the lakes would separate along the historical impairment gradient. The results show that the lakes are not separated along a gradient of impairment, and acid-intolerant taxa were collected in previously acidified lakes. There was no ameliorative intervention to combat the historical acidification and the observed recovery of water chemistry and benthos is entirely due to natural ecosystem processes. The two sampling methods (littoral kick sampling using a D-net and Hester-Dendy substrates) used to sample the benthos in these lakes can lead to substantial differences in the taxa collected.

Keywords: acidification
benthic invertebrates
Advisor: Jackson, Donald Andrew