VictorJuiz/thesis huggingface dataset:
Genetic Determinants of Plasma alpha-tocopherol
Keywords: vitamin E
alpha-tocopherol
plasma
single nucleotide polymorphism
alpha-tocopherol transfer protein
alpha-TTP
tocopherol associated protein
TAP
CYP4F2
nutrition
genetics
nutrigenomics

alpha-tocopherol is the most abundant form of vitamin E in human plasma and tissues. Inter-individual differences in plasma alpha-tocopherol concentration or its response to dietary alpha-tocopherol may be due, in part, to polymorphisms in vitamin E metabolism genes (alpha-tocopherol transfer protein (alpha-TTP), tocopherol associated protein (TAP) and CYP4F2). The thesis objectives were to determine whether common polymorphisms in the alpha-TTP (rs6994076 A>T), TAP (rs2072157 C>T and Arg11Lys) and CYP4F2 (Val433Met) genes influence plasma alpha-tocopherol concentration or modify the association between dietary and plasma alpha-tocopherol. Subjects (n=1248), 20 to 29 years from the Toronto Nutrigenomics and Health study completed a food frequency questionnaire. Fasting blood samples were used for genotyping and to measure plasma alpha-tocopherol concentration. The alpha-TTP and TAP Arg11Lys polymorphisms significantly altered plasma alpha-tocopherol. The alpha-TTP polymorphism only influenced plasma alpha-tocopherol in individuals not using supplements. None of the polymorphisms examined modified the plasma alpha-tocopherol response to dietary alpha-tocopherol.
Characterization of Disease-causing Mutations in the Chloride-Proton Antiporter ClC-5
Keywords: ClC-5
Dent's Disease

Mutations in the chloride-proton antiporter, ClC-5, cause Dent’s disease, a kidney disease defined by excessive loss of proteins in the urine. ClC-5 resides on early endosomal membranes in proximal tubule epithelial cells, where it facilitates protein receptor-mediated endocytosis. Loss-of-function mutations in ClC-5 produce proximal tubule defects in protein reabsorption. This study characterized an epithelial cell phenotype for nonsense ClC-5 mutations, R648X and R704X. Both ClC-5 mutants displayed defective biosynthesis, mistrafficking and ER localization. This study showed that ClC-5 mutations, R718X and C221R, which are also misprocessed and ER retained, are targeted for proteasomal degradation as a means to be efficiently eliminated from the ER. In addition, we have shown that a missense mutation in ClC- 5, C221R, causes a global conformational change in the antiporter, which likely reflects protein misfolding, as evident by enhanced susceptibility to trypsin proteolysis. We have characterized ClC-5 disease-causing mutations in an epithelial cell model of the proximal tubule.
Microfluidic Modeling of Cell Flow & Self-assembly of Gold Nanorods with Different Lengths
Keywords: Microfluidics
Self-assembly
Nanochemistry
Step-growth polymerization
Modeling cell flow

The thesis is divided into two parts: (1) microfluidic modeling of blood cell flow in constricted microvasculature and (2) the kinetic study of self-assembly of Au nanorods with different lengths. The passive mechanism of the flow of neutrophils was studied by using poly(dimethyl siloxane) microchannels with circular cross-sections as model blood vessels and agarose microgels as model cells. Their velocity and pressure profiles at various locations inside the microchannel with constrictions were studied as functions of (a) the initial velocity of the microgels, (b) the degree at which the channel-at-large tapered into the constriction, and (c) the size of microgels. Previously, our group proposed that the kinetics of self-assembly of Au nanorods resembles that of the reaction-controlled step-growth polymerization. To investigate factors that affect the reactivity of functional groups, self-assembly experiments were performed for nanorods with different lengths and their kinetics was analyzed.
Effect of Binder Content and Load History on the One-dimensional Compression of Williams Mine Cemented Paste Backfill
Keywords: Civil Engineering
Mining
Compression behaviour
Cemented Paste Backfill
Mine tailings
consolidation test

Large voids created by underground mining are backfilled to provide regional ground support. This thesis examines using conventional oedometer techniques and electromagnetic (EM) techniques to characterize consolidation and binder hydration in mine backfill so that EM monitoring can be used in the field to provide real-time feedback to operators to optimize the backfilling process. New techniques are given for interpreting the full range of deformation (initial compression, primary and secondary consolidation). Deformation due to initial compression is non-trivial and may have to be accounted for in numerical back-analyses of field case studies. EM parameters are sensitive to binder content, progress of hydration and loss of water caused by consolidation and binder hydration. The integrated interpretation of consolidation and EM behaviours has significant potential impact on real-time monitoring of mine backfill operations, and recommendations are made to advance the technique for this purpose.
Generation of a Murine Model for Renal Cell Carcinoma by Overexpression of HIF2α
Keywords: HIF2alpha
Hypoxia
Kidney Cancer
Transgenic Animal Model

Renal cell carcinoma (RCC) is the commonest urogenital tumor, characterized by increased expression of hypoxia inducible factors (HIFs). During normoxia, HIFα subunits are targeted for proteasomal degradation by the product of the von Hippel Lindau gene (pVHL). In RCC, mutations in the VHL gene allow the HIFα subunits to escape degradation and translocate to the nucleus where they activate transcription of their target genes. Although both HIF1α and HIF2α are upregulated in RCC, it has been suggested that HIF2α plays the dominant role. To further elucidate the function of HIF2α in RCC, we generated a transgenic mouse model that permits temporal stabilization of HIF2α in renal tubular cells. Induction of HIF2α results in the rapid development of renal cysts - a feature observed in RCC. Taken together, these results suggest that HIF2α is a key player in development of RCC and an excellent candidate target for therapy in this disorder.
Expression of Podosomes and Small-conductance Ca2+-activated K+ Channels in Cultured Microglia
Keywords: Microglia
podosomes
SK3
SK

The presence of microglia at sites of CNS injury can potentially shift the balance between neuronal survival and death; however, the mechanisms regulating their mobilization to these sites are still poorly understood. Here I report that microglia express podosomes, short-lived, punctate organelles which adhere to and degrade extracellular matrix (ECM). Podosomes and related invadopodia of cancer cells have recently been the focus of much interest for their roles in migration and invasion. Microglial podosomes degraded ECM, providing impetus for further study of their function in microglia. Further, I report the Ca2+-activated SK3 channel as a novel component of the podosome core. While SK3 and SK4 channels are reported to play redundant roles in activated microglia (Kaushal et al., 2007; Schlichter et al., 2010), immunostaining work suggests that they are differentially regulated during microglial activation. Together, these results suggest unique functions for these channel subtypes in microglia.
Investigating the Role of PHIP1 in Breast Cancer
Keywords: IGF-IR
breast cancer
PHIP1
oncogenesis

PHIP1 is a novel downstream transcriptional co-regulator of insulin-like growth factor-I receptor (IGF-IR), a tyrosine kinase receptor that is often elevated and autophosphorylated in breast cancer. In this study, I show that PHIP1 is upregulated in MCF10A cells stably overexpressing IGF-IR signaling components and that knock-down of PHIP1 significantly inhibits breast cancer cell proliferation by inducing transcriptional upregulation of p21 and downregulation of cyclin D2. I also show that stable overexpression of PHIP1 in MCF10A cells can lead to its proteasomal degradation. Together, our data indicate that PHIP1 is implicated in breast cancer cell growth and suggest a number of avenues that await exciting discovery.
The Glycemic Response Elicited by Oat β-glucan Solutions and Hard Gel Varying in Physiochemical Properties and Food Form
Keywords: Nutritional Sciences
Food Chemistry
Cereal Chemistry
Glycemic Response
Beta-D-Glucan
Viscous Soluble Fibre
β-D-Glucan
Food Hydrocolloids
Molecular Weight
Solution Volume
Food Gels
Glycemic Control
β-Glucan
Oats
Oat Fibre
Dietary Fibre
Human Nutrition
Cereal Sciences
Food Science
Glycemic Index

The ability of the soluble fibre (1->3)(1->4)-β-D-glucan to attenuate postprandial glycemic responses depends on its viscosity which, in turn, depends on molecular weight (MW) and dose. However, the effect of altering viscosity by changing solution volume is unknown. Furthermore, β-glucan solutions may form hard gels when left to age, but the effect of these gels on glycemic responses is unknown. Therefore, the effects of varying the MW and volume of β-glucan solutions and hard gels, on glycemic responses were determined. The results showed that glycemic responses were reduced by increasing viscosity by increasing MW but not by reducing solution volume. Although β-glucan gels reduced the rate of glucose diffusion in vitro, they had no effect on glycemic responses in vivo. Thus, changing solution viscosity through changes in volume does not alter the effect of β-glucan on glycemic response, and β-glucan gels are ineffective at attenuating in vivo glycemic responses.
The Effects of Continuous Positive Airway Pressure on the Work of Breathing at Rest and during Exercise
Keywords: Work of Breathing
CPAP
Exercise

Ventilation may limit exercise. Wearing a gas mask may further compromise ventilation. Continuous positive airway pressure (CPAP) improves ventilation by reducing airway resistance and thus the work of breathing. We investigated the effects of wearing a gas mask with and without CPAP on the work of breathing (WOB) during resting and exercise conditions to determine (a) whether wearing a gas mask increases the WOB and (b) whether the application of CPAP to a gas mask will mitigate (reduce) said increase to the WOB. Ten healthy males completed two test protocols with three stages each, and in three mask conditions. Physiological and dyspnea parameters were measured. Wearing a gas mask increased the metabolic cost and work of breathing. When the portable CPAP device was applied, there was no change in the calculated work of breathing, but metabolic cost of breathing was significantly reduced. CPAP also significantly reduced the sensation of dyspnea.
Roles of Irx3/5 in Mouse Hindlimb Development
Keywords: Iroquois genes
hindlimb development
prepatterning
mouse

Iroquois (Irx) homeobox genes have important and redundant functions during embryogenesis. Irx3/5 double knock out (Irx3/5 KO) mouse embryos exhibit severe hindlimb phenotypes. In these mutant hindlimbs, digit 1 and tibia are absent, moreover femur and pelvis are hypoplastic. Here, we demonstrate that Irx3/5 are expressed in the hindlimb field prior to limb bud initiation, and are required at this early stage for the pattern formation along the anteroposterior axis. Their early function is involved in prepatterning and positioning the Shh expression domain. In addition, Irx3/5 KO mutant hindlimb buds have a mild outgrowth defect and increased cell death at early stages of limb development, which may explain the small hindlimb bud size in these mutant embryos. To examine whether Irx3/5-expressing cells are the origin of lost and affected structures in Irx3/5 KO mutant hindlimbs, targeting vectors with Cre genes inserted into the Irx5 locus have been generated.
A Current Re-distribution Scheme for Improved Energy Harvesting in Concentrating Photovoltaic Systems Using Fine-grained dc-dc Conversion
Keywords: power electronics
renewable energy
photovoltaic
dc-dc converter
concentrating pv
distributed power management
delta converter
mppt
digital control
extra element theorem
simulink
lso

This thesis presents a distributed power-management architecture for concentrating photovoltaic (CPV) systems. Specifically, the Δ-conversion scheme with voltage equalization is analyzed and verified for the CPV system from Morgan Solar, Inc. This architecture uses inverting buck-boost converters, denoted Δ-converters, which equalize the voltages of neighbouring CPV cells in a series-connected string of cells and improve the systems tolerance to parameter variations. The power benefits of Δ-conversion and the Δ-converter current distributions are investigated using statistical simulations. The effectiveness of Δ-conversion in the presence of randomly distributed mismatches is demonstrated, and current cascading is identified as the main design challenge. The Δ-converter is modelled and compensated using Middlebrook's Extra Element Theorem. Analysis of measured data from a six-cell CPV system demonstrate the benefits of Δ-conversion under realistic scenarios. Experimental results from prototype systems show up to 31% power benefits in the presence of mismatches.
Source Analysis of Cortical Responses at Initial Cochlear Implant Use in Children who are Deaf
Keywords: Cochlear implants
Children
Cortical responses
Neural generators

Deafness in early development can alter how the brain responds to sound, compromising the restoration of hearing with cochlear implants. We asked how the naïve brain responds to initial cochlear implant stimulation in children who are deaf. Results indicated large variability in initial responses. Deafness associated with GJB-2 mutations led to more uniformity in cortical responses than other etiologies. Responses associated with GJB-2 mutations were characterized by a response peak with large contributions from temporal and frontal regions of the brain. This response may reflect an early stage of auditory development. By contrast, another response type, typical of normal hearing children, received less contribution from frontal regions. Through consistent cochlear implant use, frontal regions of the brain may not be as strongly recruited. Effects of deafness in early development are heterogeneous, which may reflect differences in etiology of deafness and different stages of auditory development.
Rational Modeling of Arching Action in Laterally Restrained Beams
Keywords: Arching Action
Reinforced Concrete

It is well known that arching action in reinforced concrete slabs resulting from surrounding restraining elements is responsible for much greater collapse loads than those estimated considering flexural effects only. However, the subject needs to be better understood and simplified if it is to be reliably applied in broader practice. This thesis presents a rational treatment of the problem. By limiting the scope of investigation to one-way slab systems, for the first time an explicit method of calculating the load-carrying capacity of elastic- plastic slab strips with a laterally rigidly restrained boundary condition is derived. Application of the proposed model to specimens selected from four experiment programs proves its reliability in ultimate strength calculations. The proposed model is then employed in a parametric study of structural responses of deck slab strips. The parametric study shows that a longer span, lightly reinforced deck slab system is still adequate in strength if it is cast in higher strength concrete and sufficient lateral restraint is available.
Molecular Weight Limit Identified for the Synthesis of Externally Initiated Poly(3-hexylthiophenes) and Further Macrocyclic Constructions
Keywords: poly(3-hexylthiophene)
external initiation
gel permeation chromatography
end group analysis
size exclusion chromatography
conjugated polymers
molecular weight limit
Grignard metathesis polymerization

Externally initiated o-tolyl initiated poly(3-hexylthiophene) (P3HT) was synthesized according to Grignard metathesis polymerization at varying chain length to compare number average molecular weights (Mn) obtained by gel permeation chromatography (GPC) and 1H NMR end group analysis. The extent of overestimation by GPC (1.3) was determined to be lower than previously reported for low Mn polymers. However, an apparent GPC quantification limit was observed as NMR Mn correlated well to predicted results. Static light scattering studies on high Mn polymers provided evidence that the true molecular weight was more similar to GPC-derived Mn. Despite nearly 100% external initiation efficiency, at a certain Mn limit new uninitiated chains may be synthesized. It is suggested that the synthesis of externally initiated P3HT should be limited to Mn below 40 kDa to ensure fully externally initiated chains. A proposal for the synthesis of externally initiated macrocyclic P3HT will also be discussed.
The Mechanism of Discoidin Domain Receptor 1 Mediated Vascular Calcification
Keywords: Pathology
Molecular

Introduction: Activation of Runt Related Transcription Factor 2 (RUNX2) is required for transdifferentiation of Vascular Smooth Muscle Cells (VSMCs) into a calcifying osteoblast-like phenotype. Our lab showed that deletion of Discoidin Domain Receptor 1 (Ddr1), decreased atherosclerotic vascular calcification in the Ldlr-/- mouse. Hypothesis: DDR1 regulates RUNX2 activity by affecting microtubule organization during VSMC mediated calcification. Results: Ddr1-/- VSMCs show reduced RUNX2 activity when compared to Ddr1+/+ VSMCs. Addition of the microtubule-destabilizing agent nocodazole inhibited both RUNX2 activity and nuclear localization in Ddr1+/+ VSMCs. Addition of the microtubule-stabilizing agent taxol rescued RUNX2 nuclear localization in Ddr1-/- VSMCs. Despite this, Taxol was unable to rescue RUNX2 activity as it eliminated activity in both genotypes. Conclusion: These findings indicate that under osteogenic conditions, Ddr1 deletion impedes the dynamic instability required for the maintenance of microtubule architecture. This prevents RUNX2 nuclear localization and transcriptional activation in VSMCs.
The Effect of Bonded Reinforcing Steel on Increase in Stress in Unbonded Prestressing Steel at Ultimate State
Keywords: Unbonded Prestressing
Partial Prestressing
Simplified Method

To investigate the benefit induced by adding a small amount of bonded reinforcing steel into a fully unbonded prestressed concrete beam, two well-founded and straightforward approaches for predicting tendon stress are proposed. The primary approach utilizes a flexural analysis to calculate member deformation. The supplementary approach employs a truss model to consider the additional member deformation due to shear force. Both approaches use a simplified iterative method. With these two approaches, a systematic parametric study is conducted to investigate the effects of various factors. The results indicate that adding little bonded reinforcement does significantly increase the stress increment in unbonded tendons at ultimate state for one-point loading as expected. Moreover, a lower span-to-depth ratio, the use of high-strength concrete, and a smaller mechanical reinforcement ratio also raise the stress increment.
Design of a Power Scalable Capacitive MEMS Accelerometer Front End
Keywords: Accelerometer
Interface
Power
Front End
Front-End
Power Scalable
Power-Scalable
MEMS

This thesis presents the design, implementation and fabrication for a 0.13μm interface to a capacitive MEMS accelerometer. By varying the number of amplifier slices used in concurrence based on different full scale input ranges, the analog circuitry power scales as the input range scales. Due to the oversampling nature of typical accelerometer front ends, for a full-scale input increase of N times, the analog circuitry power reduces by N2 times. The front end has two signal amplification stages, with the first stage power scaled. The chip is 1.15mmx1.15mm and implemented in a 0.13μm CMOS process. The design was packaged with the MEMS accelerometer chip inside a 44 pin CQFP. Measured results show an output rms noise of 63μVrms in a 100Hz bandwidth. The total analog circuitry power scales very linearly with different full scale ranges. A novel simple offset removal network is also shown and confirmed via measurement results.
Management Patterns and Outcomes of Differentiated Thyroid Cancer in Ontario: A Population-based Study
Keywords: differentiated thyroid cancer
extent of thyroidectomy
volume-outcome
incidence

The incidence of differentiated thyroid cancer (DTC) is rising, but controversy exists in many aspects of its treatment. This study described the change in incidence of DTC in Ontario, variations in management including extent of thyroidectomy and the influence of provider volume, and the impact of these parameters on recurrence and thyroid cancer-specific death (TCSD). A population-based study identified all new cases of DTC between 1992-2007. The incidence of DTC increased dramatically (annual percentage change 7.6%). Linkage to administrative databases revealed that extent of thyroidectomy is influenced by various factors including patient gender, age, year of diagnosis, surgeon specialty, and hospital setting, but not provider volume. Total thyroidectomy is associated with a lower recurrence rate. There is a significant association between provider volume and recurrence, with lower volume surgeons having a higher recurrence risk. Extent of thyroidectomy and provider volume did not influence TCSD. Such variations in management may lead to disparities in health outcomes.
Shattering Kraft Recovery Boiler Smelt by a Steam Jet
Keywords: pulp and paper
kraft recovery cycle
recovery boiler
smelt shattering
steam jet
atomization
droplet size
smelt-water explosion
dissolving tank explosions
water-glycerine solution
air jet
shatter jet velocity effect
liquid flow rate effect
viscosity effect
shatter jet nozzle proximity effect

Kraft recovery boiler smelt is shattered into small droplets by an impinging steam jet to prevent smelt-water explosions in the dissolving tank. Inadequate shattering increases the likelihood of dissolving tank explosions. While industry has not dedicated much effort to smelt shattering, the safety implications require smelt shattering to be studied in detail. An experimental set-up was constructed to simulate the shattering operation using a water-glycerine solution and air instead of smelt and steam respectively. The objective was to examine how physical properties and flow characteristics affect shattering. It was found that increasing shatter jet velocity greatly reduced droplet mean diameter. Increasing the liquid flow rate greatly increased droplet size, as expected. Shattering was not significantly affected by viscosity, unless a weak shatter jet was used on a highly viscous fluid. Increasing the proximity of the shatter jet nozzle decreased droplet size.
The Utility of Contrast-enhanced Ultrasound in the Assessment of Solid Small Renal Masses
Keywords: Contrast-enhanced ultrasound, microbubble contrast agent, solid small renal mass, kidney, cancer, Definity

Purpose: To compare hemodynamic of malignant and benign SRMs on CT and CEUS. Method: Seventy biopsy proven SRM underwent CEUS. Sixty-three had CT. After injection of 0.2 ml of Definity, 3min and after 0.9 ml infusion, 30 sec of data were acquires. Lesion hemodynamics relative to the cortex was evaluated both qualitatively and quantitatively. Results: Considering 15 and 20 HU as enhancement threshold, 10% to 13% of patients did not enhance on CT, while all lesions enhanced on CEUS. Papillary RCCs showed hypovascularity with 100% specificity. In other RCCs, PI, WI slope 5 to45%, 50 to100%, 10 to 90%, WO slope 100 to 50%, 100 to 10%, WO intensity at peak+30 seconds were statistically higher than benign SRMs. Conclusion: All solid SRMs enhance on CEUS, while CT does not show vascularity in 10-13% of solid SRMs. CEUS can differentiate malignant from benign SRMs by evaluating their hemodynamics.