VictorJuiz/thesis huggingface dataset:
Estrogens, Inflammation, and Cognition: Does Inflammation Mediate Verbal Memory Deficits Observed in Surgically Menopausal Women?

Women who have had an oophorectomy prior to spontaneous menopause experience a decline in E2 production and are more susceptible to dementia (Sherwin, 1988; Farrag et al., 2002; Gervais et al., 2020). Women with Alzheimer’s disease (AD) display elevated levels of inflammation compared to age-matched controls (Trollor et al., 2001; Lee et al., 2018). This study investigated the role of inflammation in mediating verbal memory deficits observed in surgically menopausal women. Our analyses revealed that women with a bilateral salpingo oophorectomy (BSO) experienced significantly greater verbal memory decay in the Logical Memory task and had significantly higher levels of CRP, IL-1????, IL-8, IL-18, and MCP-1 compared to pre-menopausal age-matched controls and/or women with a BSO taking E2 related hormone therapy (BSO + E2). Furthermore, MCP-1 mediated the difference in verbal memory decay between the BSO and BSO + E2 groups.

Keywords: cognitive decline
cytokines
estradiol
inflammation
memory
oophorectomy
Advisor: Einstein, Gillian
The Potential Role of Cyclooxygenase-2 as a Folding Factor of Vascular Endothelial Growth Factor

Secreted proteins contain disulfide bonds to support the structural three-dimensional fold. Known pathways for disulfide bond formation are dependent on oxygen, but vascular endothelial growth factor (VEGF) is among proteins that fold and function under hypoxia. We previously identified the oxidoreductase cyclooxygenase 2 (COX2) as a potential interactor with VEGF in the secretory pathway, and we propose that COX2 supports VEGF folding. Here we established models to address this, including a CRISPR-Cas9 mediated COX2 knockout cell line. Preliminary data suggest that COX2 is required for efficient disulfide bond formation and secretion of VEGF both under normoxic and hypoxic conditions. This research aims to discover a novel protein folding pathway that will give insight into protein assembly in the ER in normoxia and hypoxia.

Keywords: Cancer
Cyclooxygenase-2
Disulfide Bonds
Hypoxia
Vascular Endothelial Growth Factor
Advisor: Koritzinsky, Marianne
Characterization of Inter-neuronal Communication by Material Exchange between Primary Photoreceptors In Vitro

Recent discoveries in retinal transplantation have reframed our understanding of photoreceptor communication. The presence of pre-labelled donor cells in recipient retinas was assumed to be synaptic integration of transplanted cells but is now reinterpreted as intercellular material exchange (ME) between donor and recipient cells. The transfer of cytosolic material via membranous protrusions is known to occur in a number of cell types; however, the mechanisms and functional relevance are unclear. In this study, we established an in vitro model of primary retinal neurons to investigate the mechanisms behind ME. We observed intercellular transfer of proteins and mitochondria via neurite-like protrusions between primary photoreceptors. We propose that ME occurs through a mechanism involving cytoplasmic continuity and membrane fusion and is modulated by Rho GTPase cytoskeletal remodelling. The findings of this study contribute to expanding our understanding of inter-neuronal communication between retinal cells and its implications in retinal function and pathology.

Keywords: cell communication
material exchange
photoreceptors
retina
tunnelling nanotubes
Advisor: Wallace, Valerie A
Design of Optical based Pressure Transducer for use in Harsh Environments

In this thesis, a prototype of a low cost optical pressure transducer for use in harsh environments (temperatures up to 350◦C and pressures up to 10,000 PSI) was developed. Minimizing changes to the transducer body design, a setup replacing the previous strain-gauge based system with an optical interferometer and a low cost external signal demodulator that converts the light signal into a pressure reading, a ferrule that holds the optical system inside the transducer and aligns the fiber optic cable at the center of the diaphragm at a specified cavity distance. The thesis explores the use of the fringe-counting algorithm to detect cavity depth change, which changes as a response to applied pressure. A novel bi- directional fringe counting algorithm utilizing the mean voltage signal for direction determination was introduced and evaluated for use.

Keywords: Demodulation
Fabry Perot
Fringe counting
Advisor: Sullivan, Pierre
Exploring Cell-free Synthetic Biology Tools for De-centralized Diagnostics and Protein Manufacturing

Food security and disease prevention are of utmost importance in maintaining societal welfare. This work outlines some strategies to tackle these issues through the use of cell-free technologies. These include development of sensors for detecting Classical Swine Fever and colistin resistance genes, as well as advancement of capabilities for manufacturing of therapeutics and lab reagents. Classical Swine Fever poses a major threat to global food supply and trade. In this work, construction of low-cost and portable sensors for detection of Classical Swine Fever is demonstrated with the ultimate goal of field deployment. Furthermore, building and screening of gene circuits for tracking of colistin resistance genes is showcased. This thesis also explores several parameters relating to cell-free expression and purification of protein-based therapeutics and laboratory reagents. By canvassing these applications, this work aims to help bring the power of genetically-encoded tools outside of the laboratory.

Keywords: Automated protein expression
Biosensors
Cell-Free Protein Synthesis
Diagnostics
Synthetic Biology
Advisor: Pardee, Keith I
Development and Application of a Cell Competition Assay

Cell competition is a type of intercellular communication that results in the elimination of suboptimal cells and is emerging as an important biological phenomenon in a number of contexts, including embryonic development and cancer. To date, the rules that govern mammalian cell competition are still largely elusive. Here we report an optimized workflow to establish and validate a scalable, image-based, in-vitro assay to probe cell competition. Our pipeline integrates aspects of previously published studies to guide the design of assay parameters, including, but not limited to, the choice of cellular model and seeding conditions, competition metrics, and suitable experimental controls. We demonstrate the application of our workflow on a system of cancer cell competition triggered by differences in the expression levels of the proto-oncogene c-Myc. The feasibility of this workflow makes it an attractive platform for the medium- to high-throughput studying of mammalian cell competition using high-content imaging.

Keywords: Apoptosis
Cell Competition
CRISPR
Genetic Screening
Myc
Advisor: McGuigan, Alison P.
Development of a Perfusion Bioreactor for the Fabrication and Optimization of Bioengineered Intervertebral Discs

A therapeutic approach to treating the degeneration of the intervertebral disc (IVD) would involve the tissue engineering of a biological disc replacement using a perfusion bioreactor. Such reactors have been previously shown to improve nutrient delivery, provide beneficial forces, and support the cultivation of large 3D constructs. It was hypothesized that a perfusion bioreactor system, designed to culture IVD constructs, will be capable of generating outer annulus fibrosus (oAF) and nucleus pulposus (NP) tissues comparable to established spinner reactor cultures and improve upon static culture conditions as determined by cellular viability, nutrient delivery, and tissue formation. Perfusion grown oAF and NP tissues did not show a significant difference in ECM quantity or cellular phenotype when compared to their control conditions, maintained cellular viability at their tissue cores, and received enhanced diffusion of media throughout the tissue when compared to static conditions. This study lays the groundwork for future IVD tissues to be interfaced, scaled up, and mechanically stimulated, conditions difficult or not possible to achieve in previous culture systems

Keywords: Annulus fibrosus
Bioreactor
Intervertebral disc tissue engineering
Nucleus pulposus
Perfusion
Shear stress
Advisor: Kandel, Rita
Santerre, Paul
Multiscale Cell-to-vehicle Thermo-electrical Modelling, Simulation and Testing of Electric Vehicles: A Case Study for Battery Pack Temperature Estimation Models

Advancements in modelling of electric vehicles (EVs) are needed to improve vehicle and battery thermal performance. This thesis aims to develop a multiscale cell-to-vehicle model in MATLAB Simulink to study the effects of five battery pack temperature estimation models based on two metrics: battery thermal management system (BTMS) power consumption and maximum temperature gradient. The study considers battery packs with parallel and serial cooling delivery modes in both summer and winter conditions. These estimation models include average temperature, maximum temperature, top 10 percentile, reduced maximum temperature and reduced average temperature. This study also considers temperature sensing resolution in typical commercial EV battery packs by varying the number of temperature sensors used to estimate the two metrics. The findings from this study suggest that parallel cooling delivery mode with the reduced average temperature estimation model is best suited when considering the two metrics.

Keywords: Battery Modelling
Electric Vehicles
Advisor: Amon, Cristina C.A
Determinants of Variation in Natal Dispersal Distances amongst North American Birds

Dispersal is fundamental to many processes such as community connectivity, gene flow, and macroevolution. Natal dispersal, movement from birth site to breeding site, is usually the longest dispersal event among birds and thus the most influential to these processes. Recent work has suggested that the cost of transport may be an important factor for determining dispersal distance. I use large-scale mark-recovery data to estimate natal dispersal distances in North American birds and incorporate morphologically based flight efficiency proxies, ecological and behavioural factors into models that explain the variation of dispersal distances across species. Model inference techniques suggest that flight efficiency, population size and habitat are important for natal dispersal distance, the individual effects of which are difficult to disentangle. I suggest that since these parameters capture information about a species mobility, mobility is what determines natal dispersal distances in North American birds.

Keywords: birds
dispersal
ecomorphology
flight efficiency
wing shape
Advisor: Claramunt, Santiago
Medical Devices and the ManGo: Prototyping Low-cost, High-quality Medical and Laboratory Systems That Make Healthcare More Accessible

The COVID-19 pandemic that ravaged the world in 2020 gave light to a lot of things, but mostimportantly it highlighted how access to healthcare remains an obstacle to many, particularly to those in resource-poor areas of the world. In this work, I describe my efforts in building medical and laboratory systems that help provide high-quality healthcare with low-cost resources. My main project is the development of a portable fluidic system which takes advantage of cell-free systems to significantly reduce the time and costs associated with protein manufacturing. Two versions of this fluidic system have been developed, both of which manufacture therapeutics and research tools quickly and at low-cost. A second system I developed is an economical incubator as a companion device to augment the functionality of a glucose meter interface for diagnostics.

Keywords: Design
Fluidics
Medical System
Point-of-Care
Protein Manufacturing
Prototyping
Advisor: Sinton, David
Pardee, Keith
A Morphological and Molecular Investigation into the Role of Ethylene in Cannabis sativa Sex Determination

Commercial Cannabis producers rely on harvesting unfertilized female flowers for their high cannabinoid levels, but presence of male pollen can lead to fertilization and yield losses. Although male plants can be genetically identified, there is no reliable way to identify female plants which spontaneously produce viable male flowers. Understanding of Cannabis sativa’s sex determination mechanisms is limited, but the phytohormone ethylene is known to promote female flower development. Phenotypic analysis confirmed C. sativa responds canonically to ethylene. Microscopy revealed unisexual C. sativa flower development diverges early through distinct morphological pathways and ethylene inhibition in female plants exposed an alternative male flower formation pathway. From these, a model for C. sativa sex determination regulated by ethylene is proposed, with support from differential gene expression analyses. Future studies are needed to identify causal genes regulating sex determination so male flower-producing plants can be identified by growers, and female-only strains can eventually be bred.

Keywords: Cannabis sativa
ethylene
genetics
molecular biology
morphology
sex determination
Advisor: Lumba, Shelley
Hyperglycemia from Glucocorticoid Use for Prophylaxis of Chemotherapy-induced Nausea and Vomiting (CINV)

Chemotherapy-induced nausea and vomiting (CINV), a frequent adverse effect of chemotherapy, is debilitating and negatively impacts patients’ wellbeing. Despite the introduction of newer antiemetics, glucocorticoids continue to play a fundamental role in CINV prophylaxis. Hyperglycemia is a well-documented adverse effect of glucocorticoids, yet there is a limited systematic effort to assess its occurrence and develop strategies for its management in the oncology population. We sought to provide a better understanding of glucocorticoid-induced hyperglycemia (GIH) in the setting of CINV prevention by conducting a: (1) systematic review of the current literature; (2) retrospective chart review to ascertain current glucose monitoring practices; and (3) prospective observational study to assess the occurrence of GIH. There is a paucity of high quality evidence addressing GIH in this population. Current glucose monitoring practices do not adequately identify the magnitude of the issue in practice as GIH occurs more frequently than is documented.

Keywords: chemotherapy-induced nausea and vomiting
colorectal cancer
dexamethasone
glucocorticoids
hyperglycemia
oncology
Advisor: DeAngelis, Carlo
Lens-less In-fiber Bragg Grating (FBG) Spectrometer and Femtosecond Laser Welding-based Packaging

A femtosecond laser was applied to single-mode optical fiber to embed a periodic filament array. The filament-grating resulted in azimuthally narrowed radiation modes, while chirped grating design provided spectral focusing. This combination permitted lens-less all-fiber spectrometry, offering a high-resolution of 335 pm in the visible spectrum with a low-cost CCD camera. The diffraction efficiency was improved in two directions: increasing radiative scattering from high refractive index contrast in air-filled nanoholes and by scaling from one-dimensional (1D) to 2D designs of photonic grating structure in the core. The further objective centred on laser writing of strong pseudo-continuous weld seams for fiber-to-ferrule packaging. Parallel welding tracks were aligned azimuthally around the interface, bonding over 90% of the interface circumference. This hermetic-like welding avoided thermal degradation of FBG devices in the core. Femtosecond laser processing thus demonstrated a flexible means for optical fiber fabrication and packaging, enabling robust packaged FBG sensor for high temperature and strain environments.

Keywords: FBG
femtosecond laser
fiber
fiber welding
glass welding
laser processing
Advisor: Herman, Peter R
GLP-2 Regulation of Dietary Fat Absorption and Intestinal Chylomicron Production: The Role of the Enteric Nervous System via Neuronal Nitric Oxide Synthase (nNOS) Signalling

Postprandial dyslipidemia is a metabolic condition associated with insulin-resistant diseases. It is characterized by the overproduction of intestinal chylomicron particles and excess atherogenic chylomicron remnants in circulation. We have previously shown that GLP-2 augments dietary fat uptake and chylomicron production; however, the underlying mechanism(s) remain(s) unclear. This study investigated the role of nNOS in lipid uptake and chylomicron formation in animal models, after intraduodenal and oral fat administration. GLP-2 treatment in WT mice significantly increased postprandial lipid accumulation and circulating apoB48 protein levels, while these effects were abolished in nNOS-/- mice. nNOS inhibition in Syrian golden hamsters and PKG inhibition in WT mice also abrogated the effects of GLP-2 on postprandial lipid accumulation. This study demonstrates a novel mechanism in which nNOS-generated NO is crucial for GLP-2-mediated lipid absorption and chylomicron production. This data also implicates an nNOS-PKG mediated pathway in the effects of GLP-2 on lipid and lipoprotein metabolism.

Advisor: Adeli, Khosrow
Investigating Calcium Phosphate Growth on DNA and Protein Scaffolds

Biomineralization of mineralized tissues (e.g. teeth and bones) are highly organized and regulated processes. In particular, extracellular matrix proteins such as amelogenin (scaffold) and amelotin (mineral promoter) play crucial roles in enamel formation. Amelotin contains a short SSEEL peptide responsible for mineralization regulation. In this thesis, self-assembled scaffolds composed of amelogenin or DNA, in combination with amelotin or its SSEEL peptide, are used to investigate guided calcium phosphate deposition. Though amelogenin scaffolds provide a direct in vivo relation to enamel development, self-assembled DNA scaffolds offer the ability to arrange mineral promoting groups with nanoscale precision. This thesis shows that amelogenin and amelotin co-assemblies result in controlled hydroxyapatite (HAP) growth, while DNA nanostructures functionalized with the SSEEL peptide result in selective calcium phosphate deposition. Mineralized tissues are incapable of regeneration past a critical defect size; therefore there is a marked need for investigating biomineralization processes and for developing treatment options.

Advisor: Carneiro, Karina
Accelerated Long-term Forgetting in Parkinson's Disease and Healthy Aging

Accelerated long-term forgetting (ALF) is characterized by rapid forgetting of long-term episodic memories over hours to weeks despite normal initial learning. Emerging evidence suggests ALF occurs in Parkinson’s Disease (PD) and healthy aging. However, the few ALF studies in these groups use paradigms with high reliance on executive functions which hinders the ability to determine whether these forgetting effects are indicative of hippocampally-based episodic memory and/or fronto-executive declines. Using two long-term item memory measures that minimize demands on executive functions, I hypothesized that PD and healthy older adult groups would show greater forgetting by three days than healthy controls and younger adults respectively. Preliminary results show no significant ALF effects in either group, which may reflect the current under-powered sample or that executive functioning mediated ALF in previous studies. Notwithstanding, this research will help elucidate the relationship between ALF, hippocampally-based memory processes and fronto-executive abilities in PD and healthy aging.

Keywords: Aging
Episodic Memory
Executive Function
Forgetting
Parkinson's Disease
Advisor: Cohn, Melanie
The Impact of Dentin Conditioning and Sealer Modification with Chitosan-hydroxyapatite Nanocomplexes on the Antibacterial and Mechanical Characteristics of Root Dentin

This study assessed the effectiveness of dentin-conditioning with chitosan-hydroxyapatite-precursor (CS-HA) nanocomplexes alone or associated with tricalcium silicate sealer (TCS/CS-HA) on mechanical and antibiofilm properties in root-dentin. TCS and TCS/CS-HA characterization was evaluated. Lower premolars treated with CS-HA dentin-conditioning and/or associated to TCS were used to determine fracture resistance. Enterococcus faecalis-infected roots were utilized for antibacterial analysis. SEM findings were described. Paired t-test was used to analyse flowability results. Findings from solubility, fracture and antibacterial assays were assessed by ANOVA-Tukey’s tests. TCS/CS-HA slightly reduced flowability but did not affect solubility (p>.05). TCS/CS-HA significantly enhanced hardness/elasticity (p

Keywords: Chitosan
Dentin
Nanocomplexes
Tricalcium silicate sealer
Advisor: Kishen, Anil A.K
Exploring the Combinatorial Function of Proneural Genes Neurog1 and Neurog2 in Neocortical Development

Proneural genes encode basic-helix-loop-helix (bHLH) transcription factors (TF) that promote neural progenitor cell (NPC) differentiation in the developing nervous system. The proneural genes Neurog1 and Neurog2 are co-expressed in neocortical NPCs, yet our lab recently found that they are functionally divergent, despite their sequence similarity. The work presented in my thesis further explores the fate and function of Neurog1/Neurog2 double+ NPCs. I first showed using RNAscope that Neurog1 and Neurog2 are only co-expressed in early cortical NPCs, consistent with previous reports. I then used a novel Split-Cre lineage tracing approach, in which only NPCs co-expressing these two genes are induced to express a fluorescent reporter, to track the fate of Neurog1/Neurog2 double+ NPCs. I found that double+ NPCs give rise to intermediate neuronal progenitors (INPs) and neurons in all cortical layers. These findings provide further support for the progressive restriction model of laminar fate specification, which states that early NPCs give rise to all cortical layers, in part via INPs, while late-stage NPCs are restricted to upper-layer laminar fates. I then characterized the effects of specifically deleting only Neurog1/Neurog2 double+ NPCs, comparing to a global double knock-out (DKO) of Neurog1 and Neurog2. I found that by the end of the normal neurogenic period, in both Split-Cre;Rosa-diptheria toxin A (DTA) ‘deletor’ and Neurog1-/-;Neurog2-/- DKO cortices, NPC pools were precociously depleted. Taken together my work supports the importance of the cooperative actions of these two proneural genes to coordinately regulate the timing of cortical neurogenesis.

Keywords: neocortex
Neurog1
Neurog2
neurogenesis
proneural
Split-Cre
Advisor: Schuurmans, Carol
Exploration of Surface Properties of Engineered Sponges for Effective Marine Oil Spill Cleanup

Removing emulsified oil from seawater is challenging. Superwetting foams developed using afacile dip coating technique have emerged as a promising approach. They allow for the manipulation of surface properties to remove free and emulsified oil from seawater. Herein, new surface engineered sponges have been developed to remove different crude oils from seawater. These coatings were developed to improve performance for different oils and understand the influence of different factors on oil removal efficacy: surface chemistry, surface roughness and electrostatic compatibility. The developed materials displayed over 99% removal efficacy for light, conventional, and heavy crude oil emulsified in water, across a wide range of environmental conditions, including pH, temperature, and salinity. This approach is simple, scalable, and economical with the potential to address large-scale marine oil spills. The insights provided can provide researchers an understanding of pivotal surface properties necessary to drive emulsified crude oil adsorption when developing future materials.

Keywords: Adsorption
Crude Oil
Emulsions
Nanocomposites
Oil Spill Treatment
Advisor: Bilton, Amy M