VictorJuiz/thesis huggingface dataset:
Design and Development of Atmospheric Plasma Sprayed Ceramic Anodes for Solid Oxide Fuel Cells Operating under High Fuel Utilization Conditions

High fuel utilization SOFCs could eliminate emissions from systems that include afterburners and potentially be suitable for carbon sequestration, while producing electricity more efficiently. Current fuel utilization operating points are typically chosen at approximately 85% for Ni-cermet anodes because higher fuel utilization frequently results in the formation of nickel oxide and reduces drastically the performance of the SOFC. In this work the feasibility of an in-plane graded anode architecture with a transition from a material with high catalytic activity to materials more stable under high fuel utilization conditions was evaluated through a steady-state SOFC finite element model. Thereafter, plasma spraying of solution precursor feedstock (SPPS) and suspension feedstock (SPS) was used to fabricate ceramic coatings that could potentially be used as SOFC anodes for high fuel utilization conditions. Microstructural, electrical and electrochemical properties of LST, LSBT and LSFCr coatings with additions of carbon black pore former were investigated.

Keywords: SOFC anodes
High fuel utilization
Plasma spray
Ceramic materials
Advisor: Kesler, Olivera
Role of TAp73 in Female Reproductive Aging and Fertility

An increasing number of women delay childbearing and consequently face infertility and pregnancy complications associated with age. The central contributor to compromised reproductive performance is poor oocyte quality. Despite advances in assisted reproductive technologies, a strategy to overcome the damage that oocytes receive with age is yet to be identified. This work focuses on the influence of TAp73, a protein that decreases in mouse and human eggs with age, on the developmental capacity of mouse oocytes. TAp73 deficient mice were found to have fewer active mitochondria and compromised clearance of damaged material in their oocytes, possibly due to reduced mTOR-TAp73 axis signaling. These qualities were shown to contribute to low oocyte maturation rates. Additionally, TAp73 likely mediates the action of coenzyme Q10, which restores oocyte TAp73 levels and mitochondrial quality in aged mice. Together these findings suggest that TAp73 is a promising therapeutic target for improving oocyte function.

Keywords: fertility
oocyte
metabolism
mitochondria
aging
TAp73
Advisor: Jurisicova, Andrea
Regulation of Autophagy by Nlrp5 in Preimplantation Embryos

Previous studies have shown that NACHT, leucine rich repeat and PYD domain containing 5 (Nlrp5) deficient embryos fail to develop beyond the two-cell stage. Despite this strong phenotype, little is known of the function of NALP5 and the pathways affected by its deficiency. We showed that Nlrp5 deficient oocytes and embryos exhibit a decrease in caspase activity. In addition, the kinetics of NF-κB-p65 nuclear translocation is altered, which leads to negative downstream effects. Autophagy is known to be regulated downstream of NF-κB and is a key event during the oocyte-to-embryo transition. We observed defective execution of autophagy in Nlrp5 deficient two-cells evidenced by absence of autophagosome formation and abnormal lysosomal maturation. We found that inactivating autophagy leads to an accumulation of lipid droplets and embryos lacking Nlrp5 exhibit this accumulation. Thus, NALP5 may be an integral component responsible for autophagy mediated lipid metabolism, which when compromised causes developmental arrest.

Keywords: Nlrp5
Embryo
Advisor: Jurisicova, Andrea
Generation and Correction of a Novel Mouse Model of Farber Disease

Farber disease is a fatal inherited disorder of lipid metabolism. It is characterized by a deficiency of the lysosomal enzyme acid ceramidase (AC), resulting in the buildup of the bio-effector molecule ceramide. A previous attempt to generate a Farber mouse model by Asah1 knockout was unsuccessful owing to embryonic lethality in homozygous embryos. Here, we successfully generated viable homozygotes that developed Farber disease by introducing a single-nucleotide human patient mutation into a conserved region of murine Asah1 (P361R). Indeed, homozygotes manifested Farber disease symptoms and died within 7-13 weeks. Furthermore, treatment of neonatal pups with intravenous injections of AC lentiviral vectors (LVs) yielded homozygotes with intermediate Farber phenotypes highlighted by reduced symptoms and increased longevity. Therefore, this first model of Farber disease can facilitate the advancement of experimental therapies and offer mechanistic insights into the integral roles of acid ceramidase, ceramide, and related sphingolipids in cell signaling, growth, and oncogenesis.

Keywords: Acid ceramidase
Lysosomal Storage Disorders
Advisor: Jeffrey, Medin
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway

Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is involved in microRNA silencing, another process implicated in CD pathogenesis. MicroRNAs are short non-coding RNAs that are loaded onto RNA-induced silencing complex (RISC) and promote degradation and/or repress translation of target mRNAs. RISC formation and turnover occurs on endosomal membranes. Since autophagosomes and endosomes are closely related and RISC components are downstream effectors of microRNA silencing, I hypothesized that autophagy affects RISC, hence modulates microRNA expression. Using immunoblotting and immunofluorescence, I showed that Ago2, a critical component of RISC, is increased in cells with defective autophagy. Using microarray technology, I discovered 5 microRNAs that are differentially expressed in these cells. Taken together, my results propose a compelling mechanism by which autophagy regulates Ago2, thereby affects miRNA expression, which is implicated in the development of CD.

Keywords: Autophagy
microRNA
Crohn's Disease
Argonaute 2
RNA-induced Silencing Complex
Advisor: Jones, Nicola L.
Silverberg, Mark
Molecular Evolution of Dim-light Visual Pigments in Neotropical Geophagine Cichlids

Neotropical cichlid fishes are highly diverse and occupy diverse environments. Visual pigment evolution has been important in the diversification of African rift lake cichlids, but little is known of Neotropical cichlid visual systems. This thesis addresses the molecular evolution of rhodopsin in the Geophagini tribe of Neotropical cichlids. We use likelihood-based codon models of molecular evolution and newly isolated sequences for Neotropical cichlid rhodopsin to compare patterns of selective constraint among Neotropical, African rift lake, and African riverine cichlid rhodopsin. We provide evidence for differences in selective constraint among clades, with positive selection occurring in the Neotropical and African rift lake clades. Further, we find variation in selective constraint within geophagine cichlids. Our results suggest that Clade model C may be more appropriate than branch-site models for investigating variation in selective constraint among clades. Neotropical cichlids are emerging as an excellent system for investigating molecular evolution in visual pigments.

Keywords: Cichlid
Rhodopsin
Vision
dN/dS
Neotropical
Advisor: Lopez-Fernandez, Hernan
Chang, Belinda
Neuronal UV-Initiated Apoptosis is Prevented By 5-Bromo-2’-Deoxyuridine (BrdU) Or A Deficiency in Cockayne Syndrome B Or Xeroderma Pigmentosum A

This project addressed mechanisms of the neuronal DNA damage response after treatment with the model DNA damaging agent ultraviolet light (UV). The thymidine analogue, 5-bromo-2’-deoxyuridine (BrdU) protected against UV-initiated neuronal apoptosis in a concentration-dependent manner (p<0.001). BrdU did not protect proliferating mouse embryonic fibroblasts from UV-induced apoptosis. We assessed whether the mechanism of BrdU neuroprotection was through a modification in the neuronal DNA damage response. BrdU neuroprotection was independent of BrdU incorporation into DNA, neuronal DNA repair, p53 activation or cell cycle re-entry, a neuronal DNA damage response. Neurons deficient in Cockayne Syndrome B (CSB) or Xeroderma Pigmentosum A (XPA) were paradoxically resistant to UV-initiated apoptosis. Therefore, CSB and XPA play essential roles in the neuronal DNA damage response.

Keywords: Neuron
DNA repair
BrdU
XPA
CSB
DNA damage
Advisor: Laposa, Rebecca
The Role of the Glucagon-like Peptide-1 Receptor in Atherosclerosis

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists have been shown to reduce atherosclerosis in non-diabetic mice. We hypothesized that treatment with GLP-1R agonists would reduce the development of atherosclerosis in diabetic Apoe-/- mice. Results: Exendin-4 treatment (10 nmol/kg/day) of high-fat diet-induced glucose-intolerant mice for 22 weeks did not significantly reduce oral glucose tolerance (P=0.62) or HbA1c (P=0.85), and did not reduce plaque size at the aortic sinus (P = 0.35). Taspoglutide treatment for 12 weeks (0.4-mg tablet/month) of diabetic mice reduced body weight (P<0.05), food intake (P<0.05), oral glucose tolerance (P<0.05), intrahepatic triglycerides (P<0.05) and cholesterol (P<0.001), and plasma IL-6 levels (P<0.01); increased insulin:glucose (P<0.05); and unaltered oral lipid tolerance (P=0.21), plasma triglycerides (P=0.45) or cholesterol (P=0.92). Nonetheless, taspoglutide unaltered aortic atherosclerosis (P=0.18, sinus; P=0.19, descending aorta) or macrophage infiltration (P=0.45, sinus; P=0.26, arch). Conclusions: GLP-1R activation in either glucose-intolerant or diabetic mice does not significantly modify the development of atherosclerosis.

Keywords: diabetes
atherosclerosis
glp-1
glucagon-like peptide-1
cardiovascular disease
ApoE
mice
hepatic steatosis
Advisor: Drucker, Daniel J.
Using Flow Cytometry to Evaluate the Functionalization and Targeting of Surface Enhanced Raman Scattering Nanoparticles

The effective diagnosis of leukemia subtypes requires the detection of multiple cell surface markers. Current methods of detection use mostly fluorophores, which are limited by their large spectral bandwidths, photobleaching, and incompatibility with histological stains used for morphological assessments. Antibody-conjugated Surface enhanced Raman scattering (SERS) nanoparticles is an alternative tool that overcomes these limitations. A current drawback of SERS is the lack of available tools to analyze the bioconjugation of antibodies to nanoparticles following EDC/sulfo-NHS cross-linking, which produces inconsistent results and determines the efficacy of SERS probe targeting. This study uses the flow cytometry approach to evaluate SERS particles by incorporating FITC and DyLight650 secondary antibodies. Flow cytometry was also used to assess targeting of particles to markers on LY10 cells and CLL cells and to detect SERS signals by inserting a 710 BP 10nm FWHM filter specific for MGITC.

Keywords: Flow cytometry
Surface Enhanced Raman Scattering
Diagnostics
Leukemia
Cell labelling
Raman microscopy
Advisor: Wang, Chen
Abrogation of the Retinoblastoma Pathway Defines Clinical Outcome in High Grade Serous Carcinoma

High Grade Serous Carcinoma is the most aggressive tubal/ovarian histotype. The Rb pathway, which functions to preserve cell cycle regulation and genomic stability, is frequently deregulated in HGSC. The aim of this study was to identify non-redundant mechanisms of Rb pathway deregulation with clinical relevance. Immunohistochemistry analysis of P16 and RB1 expression identified a P16 homogeneous/RB1+ subgroup with the shortest recurrence free survival, while P16 heterogeneous/RB1+ and P16 homogenous/RB1- subgroups showed longer recurrence free survival. These P16/RB1 categories were shared between precursor lesions and the associated HGSC. Characterization of the Rb pathway in the three subgroups revealed CCNE1 amplification and highest protein expression in the P16 homogeneous/RB1+, high cyclin D1 protein expression in P16 heterogeneous/RB1+, and E2F3 amplification and highest Ki67 protein expression in P16 homogeneous/RB1- subgroup. Rb pathway deregulation is common in HGSC, occurs early in tumor development, and results from multiple non-redundant mechanisms that correlate with clinical outcome.

Keywords: ovarian cancer
clinical outcome
Advisor: Shaw, Patricia
Gauthier, Mona
Investigation of Myc-regulated Long Non-coding RNAs in Cell Cycle and Myc-dependent Transformation

Myc deregulation critically contributes to many cancer etiologies. Recent work suggests that Myc and its direct interactors can confer a distinct epigenetic state. Our goal is to better understand the Myc-conferred epigenetic status of cells. We have previously identified the long non-coding RNA (lncRNA), H19, as a target of Myc regulation and shown it to be important for transformation in lung and breast cells. These results prompted further analysis to identify similarly important Myc-regulated lncRNAs. Myc-regulated lncRNAs associated with the cell cycle and transformation have been identified by microarray analysis. A small number of candidate lncRNAs that were differentially expressed in both the cell cycle and transformation have been validated. Given the increasing importance of lncRNAs and epigenetics to cancer biology, the discovery of Myc-induced, growth associated lncRNAs could provide insight into the mechanisms behind Myc-related epigenetic signatures in both normal and disease states.

Keywords: c-Myc
long non-coding RNA
lncRNA
breast cancer
cancer biology
transcription
epigenetics
Advisor: Marsden, Philip A.
Penn, Linda Z.
Quantum Transport in InAs Nanowires with Etched Constrictions and Local Side-gating

To study transport properties in single InAs nanowires (NW) with etched constrictions, a bunch of back-gated single InAs NW devices were made. The standard device contained a NW section with an etched constriction, placed between two pre-patterned side-gates. For comparison, devices either without etched constriction or without side-gates were also fabricated. Transport measurement results of three devices were presented and discussed. The device without side-gates exhibited Coulomb blockade due to electron tunneling through double quantum dots (QDs). The device without the etched constriction displayed conductance quantization. The standard device showed both Coulomb blockade (due to electron tunneling through either multiple QDs or single QD) and Fabry-Perot conductance oscillation at different gate bias regime. A 3-D electrostatic and 2-D eigenvalue coupled simulation was conducted to explain the observed conductance quantization. This model suggests that the nonuniform potential distribution in a thick NW dramatically modifies the confinement energies in the NW.

Keywords: quantum transport
nanowires
Coulomb blockade
Fabry-Perot electron interference
conductance quantization
InAs
etched constriction
side-gating
Advisor: Ruda, Harry E.
The Utility of Admission Screening for the Prevention of Nosocomial Transmission of Extended-spectrum β-Lactamase Producing Enterobacteriaceae

Background: The efficacy of interventions to prevent in-hospital transmission of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is poorly defined, particularly for admission screening. Methods: Variability in ESBL-E infection control practices was evaluated with a survey of 15 hospitals. All ESBL-E positive clinical and screening specimens at 12 hospitals (6 screening and 6 non-screening) from 2005-2009 were included and defined as hospital-onset or community-onset using standard definitions. ESBL-E incidence and susceptibility were studied. Screening efficacy was evaluated with a negative binomial model, adjusting for study year and incidence of community-onset cases. Results: Diverse practices in infection control for ESBL-E were found with 53.3% of hospitals utilizing admission screening. Overall incidence and hospital-onset cases increased 4-fold and 2-fold, respectively. Fluoroquinolone susceptibility for E. coli (12.8%) and K. pneumoniae (9.0%) was low. Hospital-onset cases were 49.1% lower in screening compared to non-screening hospitals (p<0.001). Conclusion: Admission screening can reduce the incidence of hospital-onset ESBL-E cases.

Keywords: Admission Screening
ESBL
Advisor: Muller, Matthew
The rRole of Intestinal Scavenger Receptor Class B Type I in Chylomicron Production in Normal and Insulin Resistant States

In recent years, studies have revealed a central role for the intestine in regulation of lipid homeostasis and development of insulin resistance and type-2 diabetes. The function of intestinal Scavenger Receptor Class-B type-I remains unknown, however it is believed to play a role in dietary lipid uptake. Recently, our laboratory demonstrated a correlation between intestinal SR-BI expression and chylomicron secretion. We hypothesized that intestinal SR-BI is involved in chylomicron secretion and contributes to chylomicron oversecretion in insulin resistance. I first characterized chylomicron production in healthy and insulin resistant Syrian golden hamsters. Inhibition of SR-BI resulted in reduced postprandial chylomicron accumulation in plasma, and resistance to diet-induced hyperlipidemia and weight-gain. Lower postprandial triglyceride levels were also observed in SR-BI-/- mice. In summary, these data demonstrate a key role for intestinal SR-BI in chylomicron secretion and control of lipid homeostasis, implicating intestinal SR-BI in chylomicron overproduction in insulin resistant states.

Keywords: Lipoprotein Metabolism
Insulin Resistance
Intestinal Physiology
Scavenger Receptor Class B Type I
Advisor: Adeli, Khosrow
Rhodium-catalyzed Intermolecular Ketone Hydroacylation: Towards an Enantioselective and Diastereoselective Protocol

The addition of an aldehyde C−H bond across a ketone functionality, formally a hydroacylation, has emerged as an atom-economical approach to the synthesis of esters. While this is an efficient strategy for producing biologically-relevant materials, the field of transition metal-catalyzed ketone hydroacylation is currently limited to intramolecular systems. The development of a new rhodium catalyst will be presented, and its application to intermolecular ketone hydroacylation will be discussed. Ester products were synthesized from unfunctionalized, aliphatic aldehydes and chelating ketones in excellent yields under relatively mild reaction conditions. Efforts towards an asymmetric intermolecular ketone hydroacylation will be described, including the application of known chiral catalysts and the development of novel chiral phosphine ligands for asymmetric catalysis. Ester products were obtained in as high as 78% enantiomeric excess.

Keywords: Catalysis
Hydroacylation
Advisor: Dong, Vy Maria
Utilization of Prenatal Services by Survivors of Childhood and Adolescent/Young Adult Cancers

Objectives: To describe utilization of specialised prenatal care by high-risk survivors and evaluate echocardiogram use in echocardiogram-need survivors, as per survivorship guideline recommendations. Methods: Retrospective population-based matched survivor:control study utilizing Ontario health administrative data. Survivors were classified as high-risk/low-risk for obstetrical outcomes, and as echocardiogram-need (yes/no) for echocardiogram outcomes. Associations were tested using logistic regression. Results: 11% (n=363) of 3,204 pregnant survivors were classified as high-risk. Over 90% received specialized prenatal care. Living in a rural area was associated with lower use. (AOR 0.51; 95% CI 0.44-0.59). Since 2003, 32% (560/1,737) of survivors had an echocardiogram-need. Only 14% (77/560) had ≥1 echocardiogram, this was not associated with rurality nor neighbourhood income quintile. Conclusions: Although the majority of high-risk survivors receive specialized prenatal care, geographic inequality in care persists. Despite survivorship guidelines, >85% of echocardiogram-need pregnant survivors do not have an echocardiogram performed; future work should address this gap in care.

Keywords: Cancer Survivors
Late effects
Pregnancy
Echocardiogram
Childhood
Adolescent/Young Adults
Advisor: Guttmann, Astrid
Development of a Linear Ultrasonic Motor with Segmented Electrodes

A novel segmented electrodes linear ultrasonic motor (USM) was developed. Using a planar vibration mode concept to achieve elliptical motion at the USM drive-tip, an attempt to decouple the components of the drive-tip trajectory was made. The proposed design allows greater control of the drive-tip trajectory without altering the excitation voltage. Finite element analyses were conducted on the proposed design to estimate the performance of the USM. The maximum thrust force and speed are estimated to be 46N and 0.5370m/s, respectively. During experimental investigation, the maximum thrust force and speed observed were 36N and 0.223m/s, respectively, at a preload of 70N. Furthermore, the smallest step achievable was 9nm with an 18μs impulse. Nevertheless, the proposed design allowed the speed of the USM to vary while keeping the thrust force relatively constant and allowed the USM to achieve high resolution without a major sacrifice of thrust force.

Keywords: ultrasonic
ultrasonic motor
Piezoceramic
Piezo
actuator
USM
Advisor: Mrad, Ridha Ben
Chronic Mitochondrial Translation Inhibition Alters Metabolic Phenotype and Stemness Properties of a Leukemic Cell Line

Recently, we demonstrated that the anti-bacterial agent tigecycline preferentially induces death in leukemia cells through the inhibition of mitochondrial protein synthesis. To better understand the mechanisms of sensitivity and resistance to mitochondrial translation inhibition, we treated TEX leukemia cells with increasing concentrations of tigecycline over 4 months, and selected a population of cells resistant to tigecycline (RTEX+TIG). Compared to their wild type counterparts, the resistant RTEX+TIG cells had an altered metabolic profile with diminished oxidative phosphorylation and a greater reliance on glycolysis. Upon removal of tigecycline from RTEX+TIG cells, the cells re-established aerobic metabolism and oxidative phosphorylation to wild type levels. At the molecular level, these cells had increased levels of HIF1a. Strikingly, tigecycline-resistant cells had decreased expression of CD34 and CD117, clonogenic growth potential and engraftment capabilities in vivo. Thus, chronic inhibition of mitochondrial translation leads to the establishment of rho-zero-like metabolic phenotype, and is associated with differentiation of leukemia cells.

Keywords: mitochondria
metabolism
Advisor: Schimmer, Aaron D.
A System For Automated Vision-guided Suturing

Suturing in laparoscopic surgery is a challenging and time-consuming task that presents haptic, motor and spatial constraints for the surgeon. As a result, there is variability in surgical outcome when performing basic suturing tasks such as knot tying, stitching and tissue dissection (as large as 50\%). This goal of this thesis is to develop a standardized, proof-of-concept, automated robotic suturing system that performs a side-to-side anastomosis with image guidance and dynamic trajectory control. A passive alignment tool is created for rigidly constraining needle pose, and robust computer vision algorithms are used to track surface features and the suture needle. A robotic system integrates these components to autonomously pass a curved suture needle through sequential loops in a tissue pad phantom.

Keywords: Medical Robotics
Computer Vision
Surgical Tools
Advisor: Drake, James