VictorJuiz/thesis huggingface dataset:
The Role of Drosophila α-Catenin in Growth Regulation and EMT

α-catenin (Drosophila α-Cat) links the cadherin-catenin complex to actomyosin at adherens junctions (AJs) in epithelial cells. I investigated the role of α-Cat in proliferation control and whether α-Cat acts as a mechanosensor at the AJs to regulate Hippo signaling. I showed that α-Cat has a dosage-dependent effect on proliferation and survival. α-Cat has distinct functions in growth regulation and adhesion, acting through JNK and the Hippo pathway. α-Cat null cells undergo EMT. Intermediate loss of α-Cat resulted in overgrowth. I found that α-Cat acts as an AJ component to regulate growth. Moreover, I showed that the mechanosensitive M region of α-Cat is dispensable for adhesion and proliferation control. My work identified a novel role for α-Cat as a growth regulator at the AJs, in addition to adhesion. This work will stimulate future investigations into how the α-Cat-centered protein network contributes to growth regulation in development and cancer progression.

Keywords: adherens junctions
Drosophila
growth regulation
Îą-Catenin
Advisor: Tepass, Ulrich
Structure and Role of P. aeruginosa AlgL in Alginate Biosynthesis

During chronic infection, Pseudomonas aeruginosa generate alginate-containing biofilms in the lungs of cystic fibrosis patients. Mature bacterial alginate is a heteropolymer of Îą-L-guluronic acid and partially acetylated Î˛-D-mannuronic acid. P. aeruginosa alginate biosynthesis requires thirteen proteins, including an alginate lyase, AlgLPa, which has been proposed to have a bi-functional role, both as a lyase and as an integral part of the cell envelope biosynthetic complex. How AlgLPa performs these functions is currently poorly understood. We have used an in vitro structure-function approach to explore the substrate recognition and catalytic mechanism of AlgLPa, and in vivo complementation to explore the role of its activity in alginate biosynthesis. The results presented suggest that AlgLPa is an endo-acting lyase with at least six subsites, and that the loop containing K66 is critical for substrate binding and/or catalysis. The complementation data supports the hypothesis that AlgLPa assembles into the cell envelope biosynthetic complex.

Keywords: Alginate
Bacteria
Biofilm
Infection
Lyase
Polysaccharide
Advisor: Howell, P. Lynne
Exploring the Role of CCR6/CCL20 Axis in B Cell Migration into the CNS during EAE

B cells have been implicated in the pathogenesis of multiple sclerosis (MS) but how they migrate into the central nervous system (CNS) is poorly understood. Previous work demonstrated the use of chemokine CCL20 signaling through CCR6, in driving B cell migration during various states of inflammation. Using a transwell assay, we determined that CCR6 expressing B cells are responsive to CCL20 in a dose-dependent manner. During experimental autoimmune encephalomyelitis (EAE), CCR6 expression is upregulated on CNS-infiltrated B cells and there is increased serum concentration of CCL20. However, lack of CCR6 expression on B cells did not affect their ability to migrate into the CNS nor did it affect the severity of disease in a B cell independent model of EAE. Our data therefore suggest that the CCR6/CCL20 axis is not the main driver of B cell migration into the CNS during EAE.

Advisor: Gommerman, Jennifer L
Like Mother, Unlike Daughter: Perspectives and Relationships Between Missionary Women in Korea and Korean Women, 1884-1910

Building off of previous debates concerning missionary women and their interactions with race and gender, this thesis re-examines the perspectives and relationships between missionary women in Korea and Korean women between the years 1884-1910. I will primarily focus on the use of rhetoric in published missionary writings and the private papers of Mattie Wilcox Noble and Edith McRae to argue that the rhetoric of sisterhood was mostly used for recruitment purposes and missionary women conceptualized their relations with Korean women based on the domestic ideologies of motherhood. They saw their relationship with Korean women as similar to that of mother and daughter while at the same time also believing their role to be that of a model of motherhood for Korean women. The Korean women did not always view the relationships in the same way, which made the missionary women uneasy, and often understood their relations on a more professional basis.

Keywords: Korean history
missionaries
motherhood
race
sisterhood
women
Advisor: Schmid, Andre
Fatty Acid Sensing in the Dorsal Vagal Complex and Regulation of Triglyceride-rich very Low-density Lipoprotein Secretion

Fatty acid sensing in the hypothalamus lowers hepatic glucose production and secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG). However, whether other brain regions can sense fatty acids to regulate hepatic nutrient metabolism is unknown. Here, we demonstrated that oleic acid infusion into the dorsal vagal complex (DVC) lowers the rate of VLDL-TG secretion in rats. Given that long-chain acyl-CoA synthetase (ACSL)-mediated esterification of long-chain fatty acids (LCFAs) to LCFA-CoA is necessary for hypothalamic fatty acid sensing to lower glucose production, we next examined the role of ACSL in DVC fatty acid sensing. We found that all five ACSL members (ACSL1, 3-6) are expressed in the DVC at the protein level. Chemical inhibition of ACSL in the DVC prevented a DVC infusion of oleic acid from lowering VLDL-TG secretion. These data introduce the DVC as a novel site of fatty acid sensing in the regulation of hepatic VLDL-TG secretion.

Keywords: brain
nutrient sensing
VLDL-TG
Advisor: Lam, Tony K. T.
Vibrational Spectroscopy in Liquid Core Waveguides

In this thesis, we report an approach which significantly enhances Raman sensitivity through the formation of a thin film atop of a Photonic Crystal Fiber (PCF). With the proposed technique we were able to achieve a 40X increase in contaminant signal to background ratio for Alumina, making it much easier to detect small concentrations of solute. Moreover, Alumina was further characterized to discern whether the grain size and crystalline orientation would affect the Raman spectrum and why. Lastly, we pave the way for Liquid -Core -Waveguide (LCW) nanoparticle detection utilizing Fourier Transform Infrared Spectroscopy (FTIR) and show how a larger path length coupled with a non-absorbing background liquid can lead to an improved contaminant detection method. We were able to conduct this experiment by utilizing a mixture of Acetone and Water. A 2.72X increase in the area of the water modes was observed from a 0.5 mm to 3 mm path length increase.

Keywords: Liquid
Raman
Spectroscopy
Waveguide
Advisor: Helmy, Amr S
The Role of miR-193b-5p in LPS- and Influenza-Induced Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a fatal complication of sepsis and influenza. Aberrant microRNA (miR) expressions has been linked to the pathophysiology of ARDS and may serve as novel therapeutic targets. We have identified miR-193b-5p, not previously known to play a role in ARDS, to be a regulator of the junctional protein occludin, and significantly increased in response to pro-inflammatory stimuli both in pulmonary endothelial cells and in murine lungs. Inhibition of miR-193b-5p in vivo by anti-miR delivery prevented LPS-induced vascular leakage in mice by preserving alveolar capillary barrier function, which may be mediated by decreased occludin mRNA degradation. In parallel, miR-193b-5p inhibition in influenza A-infected mice reduced 7-day mortality and improved vascular barrier integrity compared to placebo controls. miR-193b-5p inhibition also decreased viral mRNA production and increased expression of type I interferon stimulated genes, suggesting that it may play a role in the innate antiviral response.

Keywords: ARDS
influenza
microRNAs
miR-193b-5p
occludin
sepsis
Advisor: dos Santos, Claudia C
Integration of a MEMS-based Autofocus Actuator into a Smartphone Camera

This thesis presents the design and integration of a phone camera module with a MEMS actuator to achieve autofocus. The resulting camera module addresses issues associated with the commercially available autofocus actuators such as low speed and high power consumption. The MEMS actuator is capable of moving a 62 mg load a stroke of 100 Îźm. Optical simulations were carried out to study the feasibility of achieving the autofocus within the 100 Îźm focus range. A driving circuit for the MEMS actuator was developed. An autofocus control algorithm integrating the MEMS actuator was developed based on the contrast detection method. A highly compact camera module was successfully constructed and its performance demonstrated after all its components were integrated which include the image sensor, the lens barrel, the MEMS actuator and the housing. Recommendations for further improvement of the developed camera are also included.

Keywords: Autofocus
Camera module
Integration
MEMS actuator
Advisor: Ben Mrad, Ridha
Investigation and Development of Bioelectrical Impedance Measurements in Relation to Obstructive Sleep Apnea

Bioelectrical impedance analysis (BIA) is a non-invasive technique to measure the fluid content of various tissues. Based on Ohmâ s law, tissue impedance is determined by passing a current through the tissue and measuring the voltage. The total impedance is composed of multiple parameters: the resistance, and reactance, or magnitude and phase angle, all of which may vary based on tissue composition. For example, an increase in fluid volume will result in a lower resistance, while a lower phase angle has shown to be associated with a lower muscle mass and increased mortality in heart failure patients. We demonstrate that BIA measurements of the neck are able to detect changes in the fluid content, from before to after sleep, as well as differentiate patients who show worsening in sleep apnea severity subject to fluid overloading. Furthermore, we propose a design for a portable device to measure BIA in a clinical setting.

Keywords: Bioelectrical Impedance
Fluid Overloading
Medical Devices
Obstructive Sleep Apnea
Phase Angle
Advisor: Popovic, Milos R
Yadollahi, Azadeh
The Role of Septins during Invasion of Host Cells by Salmonella enterica serovar Typhimurium

Salmonella enterica serovar Typhimurium (S. Typhimurium) initiates invasion of host cells using a Type 3 Secretion System to translocate bacterial virulence proteins (known as effectors) across the host cell plasma membrane. The effectors manipulate host cell machinery to induce actin cytoskeleton rearrangements that lead bacteria internalization. Previous studies have demonstrated the importance of host actin interactors in bacterial invasion, but how these factors are dynamically coordinated remains unclear. In my thesis, I demonstrate that septins, a conserved family of GTPases, are recruited to sites of bacterial invasion and are required for efficient bacterial internalization. Septins also promote recruitment of ROCKII kinase to invasion sites and its downstream activation of the actin nucleating protein FHOD1. In contrast, myosin II activation, known to be required for S. Typhimurium invasion, was not septin-dependent. Collectively, my data provide new insight into the mechanisms by which host actin regulatory proteins contribute to S. Typhimurium invasion.

Keywords: Invasion
Pathogenesis
Salmonella
Septin
Advisor: Brumell, John H
Team Level Factors Affecting Innovation in Multidisciplinary Capstone Design Course

Multidisciplinary capstones form student teams from different engineering disciplines to design, build, and test proof of concepts for an industry based project. To provide insight on multidisciplinary capstone’s performance and innovative outcomes, we explored innovation and factors related to innovation in both multidisciplinary and monodisciplinary capstones at the University of Toronto. Our investigation includes self-reported data and data from external assessments. We conducted both quantitative and qualitative research by collecting data from surveys, interviews, and video-recordings. External examiner’s and self-reported data show that multidisciplinary students are more innovative than mono-disciplinary ones. Our results show correlation between innovation and psychological safety, collaborative learning, internal and external communication, support for innovation from all parties, vision and feedback. Our research shows that aside from team’s diversity, support for innovation and culture of innovation is essential to realization of student’s creativity potential.

Advisor: Behdinan, Kamran
Monolithic Photon Pair Separation

The thesis analyzes integrated, planar symmetric and non-symmetric three input-output couplers for single photon pair separation. Device inputs are SPDC light sources which produce photons in pairs. The effect of two photon pair inputs on device performance is analyzed via a performance quantifier. The quantifier depends on SPDC pump power, device and input state parameters. The performance of the directional coupler is compared to the performance of the three waveguide devices via maximization of performance quantifier values with respect to device and input state parameters. It is found that the planar three waveguide devices do not offer any improved performance for photon pair separation. New approach to calculating output probabilities of mode-coupled devices is presented and can be used for other types of mode-coupled devices.

Keywords: Coupler
Integrated
Optics
Photon
Separation
SPDC
Advisor: Helmy, Amr S
Reoperation for Inguinal Hernia Recurrence in Ontario: A Population-based Study

Objective: To compare the rate of reoperation for recurrent inguinal hernia after primary repair. Methodology: A population-based retrospective cohort study, using administrative data including adult patients in Ontario, Canada undergoing primary inguinal hernia repair (IHR) from April 1, 2003 - December 31, 2012, followed to August 31, 2014. Exposure: Primary IHR techniques: open repair with mesh; open repair without mesh; laparoscopic repair Results: We identified 109,106 adults undergoing primary IHR with 5.6 year median follow-up. The 5-year cumulative risk of recurrent IHR was 1.7% in the open with mesh group, 3.2% in the open without mesh group and 3.0% in the laparoscopic group. After adjusting for patient, surgeon and institution factors, as compared to patients undergoing open repair with mesh, those undergoing open without mesh or laparoscopic repair had higher risk of recurrent IHR (hazard ratio 1.53, 95% CI, 1.33- 1.77 and 1.88, 95% CI, 1.61- 2.20 respectively, p

Keywords: Hernia recurrence
Inguinal Hernia
Laparoscopic Hernia
Lichtenstein
Advisor: Baxter, Nancy N
Detection and Online Classification of the Near-infrared Spectroscopy Fast Optical Signal for Brain-computer Interfaces

Near-infrared spectroscopy (NIRS) can detect a fast optical signal (FOS), corresponding to optical property changes in neuronal tissue during neuronal activation. The FOS has high temporal and spatial resolution, but has a low signal-to-noise ratio. The FOS has yet to be automatically classi- fied, hence its value as a BCI control signal remains unknown. During offline and online sessions, participants performed a visual oddball task. In offline sessions, the FOS was validated with elec- troencephalography (EEG) measurements of event-related potential (ERPs). Spectral relationships between FOS and ERP oddball responses were found in upper delta and theta bands using coherence and Granger causality metrics. A temporal FOS-ERP correlation was also found 200 ms after oddball presentation. Offline and online FOS classification of oddballs versus frequent responses was achieved with average balanced accuracies of 62 Âą 5% and 63 Âą 6%, respectively. FOS classification results were above chance but did not reach the threshold (>70%) for effective BCI communication.

Keywords: brain-computer interface
electroencephalography
event-related potential
fast optical signal
near-infrared spectroscopy
prefrontal cortex
Advisor: Chau, Tom
A Gold Nanoparticle-Based Assay for The Measurement of Nitrite and Nitrate Levels for Soil Macronutrient Measurement

Soil conditions are a key parameter that determines yield and quality of the crops harvested from it. The levels of nitrates, phosphates and potassium are the essential nutrients regarding soil, and most developing parts of the world do not have the luxury to perform any sort of soil analysis. Commercially available soil test kits were tested for their quantitative ability, but were found to be inadequate for regular soil testing in all parts of the world. This project takes a step towards addressing this problem by developing a nitrite/nitrate sensor that is precise, accurate and cost efficient using gold nanotechnology. While the platform is promising for widespread commercial soil testing, particularly in developing nations, the reaction has to be performed at 95oC for 1 hour. The alternatives for improving the kinetics of the reaction to allow its implementation at lower temperatures and over shorter times are presented.

Keywords: Gold
nanoparticle
Nanotechnology
Nitrate
Nitrite
Sensor
Advisor: Ramchandran, Arun
Comparative in Vitro Studies of Folic Acid versus 5-methyltetrahydrofolate Supplementation in Human Colorectal Cancer Cells

High folate status from high folic acid (FA) intakes may have unintended and serious deleterious effects on human health, such as increased cancer progression and epigenetic changes. Some studies suggest that supplementation with 5-methyltetrahydrofolate (5MTHF) may be a safer means of providing folate supplementation. We compared the effects of FA versus 5MTHF supplementation on cellular growth, intracellular folate concentrations, and expression of genes involved in folate metabolism and one-carbon transfer reactions in human HCT116 and Caco-2 cell lines. 5MTHF supplementation generally resulted in significantly faster cellular proliferation and higher intracellular folate concentrations in both cell lines. 5MTHF supplementation also resulted in higher global DNA methylation in Caco-2 compared to FA, while the opposite occurred in HCT116. No conclusive comparative effects of FA versus 5MTHF supplementation on gene expression were observed. Future studies are warranted to determine which form of folate is a more appropriate and effective for improving folate status.

Keywords: 5-methyltetrahydrofolate
5MTHF
FA
folate
folic acid
Advisor: Kim, Young-In
Emulsification by Penetration of Particles from Water into Diluted Bitumen

In this work, we demonstrate that the fine droplets of water in bitumen could be formed by the penetration of a particle from process water into diluted bitumen under the influence of an impinging force. The sizes of the smallest emulsified droplets produced in the experiments were close to 1.9Âľm. A careful examination of the penetration process revealed two broad categories of emulsification mechanisms: pinch-off and residual tail emulsification. It was also found that the residual tail emulsification mechanism was induced by surfactant mediated tip-streaming. At higher Ď , the disintegration of fine threads resulting from the penetration process lead to the formation of satellite and sub-satellite formation of sizes 2-3 Âľm. The observations and trends from this work were used to examine the possibility of emulsification via the penetration mechanism on the industrial scale, and potential emulsification locations in the froth treatment section of bitumen production were identified.

Advisor: Ramchandran, Arun
3D Block Modeling of Geomechanical Properties using Conditional Simulation Method

A thorough understanding of in-situ rock mass geomechanical properties is a key factor for a safe and efficient design of a mining project. Geomechanical properties in a mining project are generally quantified using sample data collected during site investigation. In many mining projects, an exhaustive site investigation to characterize the rock mass properties is impossible. Hence, it is crucial to model the spatial variability of rock mass geomechanical properties using the limited data. This thesis proposes and implements geostatistical simulation approaches for modeling of geomechanical heterogeneity of the rock masses in an iron ore open pit mine. 3D block models for geomechanical properties in different pit areas are generated and verified using statistical methods. The 3D geomechanical models allow the heterogeneity of rock masses to be involved in open pit mine planning and design, as more accurate knowledge of spatial distribution of geomechanical properties promotes safe and economic mine operation.

Advisor: Esmaeili, Kamran
Cognitive Sequelae of Endocrine Therapy for the Treatment of Breast Cancer

Consistent with research implicating estrogens in neuroprotection and cognitive functioning, there is accumulating evidence that endocrine therapy (ET) is associated with cognitive impairments in breast cancer (BC) patients. However, which cognitive functions are most affected by ET is not well understood and there is a lack of knowledge regarding how these agents affect cognition in older patients, who may be most vulnerable to these effects. This thesis contains two studies designed to address these issues. The first is a meta-analysis that quantified the effects of ET on various cognitive domains, and the second study prospectively examined the cognitive effects of ET in a cohort of older patients. The results of these studies converged to suggest a specific adverse effect of ET on verbal memory, a domain that has established clinical utility as an early predictor of dementia. The cognitive implications of ET treatment should be considered in clinical decision making.

Keywords: Breast Cancer
Cognition
Endocrine Therapy
Estrogen
Neuropsychology
Advisor: Tierney, Mary C
Investigating the Role of Amino Acid Transporter SLC6A14 as a Modifier of Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis

The most common disease causing mutation in CF is F508del, however there is considerable variability in the clinical phenotype of patients homozygous for this mutation. To address this variation, genetic modifiers are studied. Li et al found that SNPs in the putative promoter region of SLC6A14 were significantly associated with severity and age of first Pseudomonas aeruginosa lung infection in CF. Experiments were aimed at studying if SLC6A14-mediated amino acid uptake is regulated by bacterial pathogens and in turn regulates bacterial growth. Arginine uptake from the ASL of non-CF and CF primary bronchial cultures was measured, after treatment with purified flagellin from Pseudomonas. This treatment resulted in a 26.4% (n=5; p

Keywords: Amino Acid Transporter
Arginine
Cystic FIbrosis
Modifier Genes
Pseudomonas aeruginosa
SLC6A14
Advisor: Bear, Christine E
Experimental Evolution to Identify Mutations that Compensate for Loss of Xenogeneic Silencing Proteins in Salmonella Typhimurium

Horizontal Gene Transfer (HGT) is an important process that has driven the evolution of bacteria, and has been particularly important in the development of pathogenic strains. Foreign genes, however, pose a considerable risk to bacteria. The foreign gene silencing proteins H-NS and StpA buffer the fitness costs associated with HGT. To gain insight into how these proteins act as global regulators and to observe the functional consequences of losing these proteins, I employed an in vitro evolution approach with Salmonella strains harbouring deletions in both hns and stpA. I show that passaging over 500 generations partially restores fitness and using whole genome sequencing, identify recurring mutations within chaperones DnaK/DnaJ and the transcription termination factor Rho. My results provide important insights into how H-NS/ StpA likely coordinate with Rho to silence foreign genes and regulate HGT.

Advisor: Navarre, William W