VictorJuiz/thesis huggingface dataset:
In-situ Microrobot Fabrication Using Magnetic Guidance

Mobile microrobots are typically fabricated in a multi-step microfabrication process and then transported into an enclosed workspace for operation. In this thesis an in-situ microrobot fabrication method is presented by magnetically bending a polymer filament into a desire shape as it is fed through a hot needle which is inserted into the workspace. The mechanics of filament bending and the behavior of the bending zone is studied. A shape planner is developed for automated fabrication control of a desired shape. The capability of the method in shape creation is also analyzed. Millimeter-scale planar and 3D robotic devices of different shapes are fabricated using the developed fabrication system prototype. Functional microrobotic devices are also created to show the utility of the fabrication method for creating complex microrobot shapes remotely in enclosed environments for advanced microrobotic applications.

Keywords: bending
fabrication
in-situ
magnetic
microrobotics
Advisor: Diller, Eric D
Associations of Circulating Second Messenger Glycerophosphatidylcholines with Cardiovascular Disease Risk Factors in Adolescents

Circulating glycerophosphatidylcholines and their second messenger metabolites (smGPCs) are phospholipids that modulate risk for cardiovascular disease (CVD). CVD is a slow-progressing disease culminating by acute vascular events or chronic vascular conditions in middle-to-late adulthood, but its pre-clinical stages may already occur during adolescence. We investigated whether circulating smGPCs are associated with CVD risk factors – excess visceral fat, elevated blood pressure, insulin resistance, and low-grade inflammation – in a population-based sample of adolescents as part of the Saguenay Youth Study. Several of the smGPCs were associated with multiple CVD-risk factors and may serve as novel biomarkers of early CVD development; the most significant of these were PC(16:0/2:0) and LPC(14:1/0:0). Mediation tests revealed that PC(16:0/2:0) mediated the directed relationship between VF and blood pressure or C-reactive protein, and LPC(14:1/0:0) mediated the directed relationship between VF and fasting insulin. Elucidating pathways regulating circulating levels of these smGPCs may provide new pharmaceutical targets of CVD.

Keywords: Cardiovascular disease
Inflammation
Lipidomics
Lysophosphatidylcholine
Obesity
Platelet-activating factor
Advisor: Pausova, Zdenka
Predictors of Cancer Cell Response to Metformin

There is great interest in transitioning the antidiabetic drug metformin for use in cancer, with evidence suggesting it can improve outcome following radiotherapy (RT). Its benefit may arise from inhibiting cancer cell proliferation, abrogating tumour hypoxia through respiratory inhibition, or directly radiosensitizing cancer cells. With metformin entering clinical trials, it is crucial to identify relevant biomarkers for patient benefit. AMPK and p53 were previously identified to facilitate metformin's radiosensitization, while OCT and MATE transporters mediate its intracellular concentration: we thus investigated these as contributors to metformin's radiosensitizing, anti-proliferative, or respiratory-inhibitory effects. We found that loss of AMPK or p53 exacerbated sensitivity to metformin's inhibition of proliferation, while OCT expression was sufficient to confer response to metformin's respiratory inhibition. Together, loss of AMPK and p53 signaling, and OCT expression, represent putative biomarkers of response to inhibition of proliferation and respiration, respectively, and may be further explored in a clinical setting.

Keywords: Biomarkers
Cancer
Drug Repositioning
Metabolism
Metformin
Radiotherapy
Advisor: Koritzinsky, Marianne
Longitudinal Measures of Lung Function in Healthy Infants

Effective treatment of paediatric pulmonary disease relies on early diagnostics, and thus requires pulmonary function testing. Before infant pulmonary function testing can be applied to detect disease, it must first be understood in health, especially in the context of the developing lung. Adult studies have suggested that the rapid expansion of alveoli leads to faster growth in the lung parenchyma with respect to the conducting airways. By longitudinally evaluating lung function parameters that approximate the size of the parenchyma and the airways in infants, it can be determined whether dysanapsis is present in this young age group. However, while we were unable to find functional dysanapsis in tidal breathing measures, it was found when comparing forced flow and volumetric measures. This indicates that while the airways are proportionally larger in youngest infants, rapid parenchymal expansion leads a decrease in the relative size of these airways compared to overall lung volume.

Keywords: Infant Lung Development
Longitudinal
Multiple Breath Washout
Physiology
Pulmonary Function Testing
Advisor: Subbarao, Padmaja
The Effect of Paternal Folic Acid Supplementation on Folate Concentrations and DNA Methylation of the Offspring in a Mouse Model

Background: DNA methylation is programmed during embryogenesis, and folate is critical in the one-carbon transfer reactions. Maternal folic acid (FA) supplementation has been shown to significantly modify offspring DNA methylation. However, the role of paternal folate status is unknown. We investigated the effect of paternal FA supplementation on offspring DNA methylation. Methods: Weanling male C57BL/6 mice (n=20) were randomized to 2 or 20 mg FA/kg diets. After 3-4 weeks, breeding began with females on the control diet. At birth, pups were sacrificed, and plasma and tissues collected. Folate concentrations were determined by standard microbiologic assay, and Ppar-a, Ppar-g, Gr and Igf-2 methylation by bisulfite conversion and pyrosequencing. Results: Paternal supplementation significantly decreased the breeding period (p

Advisor: Kim, Young-In
Molecular Phylogeny of the Neotropical Knifefishes of the Order Gymnotiformes (Actinopterygii)

The order Gymnotiformes, the Neotropical electric knifefishes, is comprised of 200+ species divided into the families Apteronotidae, Gymnotidae, Hypopomidae, Rhamphichthyidae, and Sternopygidae. These species inhabit a variety of freshwater habitats throughout Central and South America. To date, attempts at resolving the internal relationships of Gymnotiformes have yet to produce an unambiguous species-level phylogeny. In order to resolve the phylogeny, I collected molecular data from seven nuclear and two mitochondrial genes for 197 species and performed parsimony and Bayesian phylogenetic analyses. All families were recovered as monophyletic with the exception of Gymnotidae; the electric eel Electrophorus, previously considered a member of this family, was instead found to be sister to all other Gymnotiformes. The topologies resulting from this study provide a highly-resolved species phylogeny which will form the basis for future studies of species diversification and ecological and evolutionary patterns.

Keywords: Evolution
Gymnotiformes
Phylogeny
Systematics
Advisor: Lovejoy, Nathan R.
Microfluidic Device for Co-culturing Lung Airway Cells on a Suspended Hydrogel: Towards a Biomimetic Lung Airway Model

Organ-on-a-chip technologies have made significant strides in recapitulating the complex multicellular 3D architectures, tissue-tissue interfaces and the physiologically relevant mechanical and biological properties of in vivo tissue microenvironments. To accelerate current drug development processes, new and improved in vitro models that reconstitute the complex in vivo microenvironment of human tissues are needed. Local disruptions to the lung airway epithelium are known to elicit specific cellular responses leading to the progression of a myriad of respiratory diseases, making it a crucial target for conducting disease mechanism and drug development studies. We aimed to develop and perform preliminary assessment on a microfluidic-based in vitro model that mimics the in vivo tissue microenvironments of the human airway. By leveraging microfabrication techniques and surface tension principles to integrate co-culture of airway cells on stable air- liquid interfaces, we demonstrated a microfluidic platform that allows more efficient 3D culture experiments and enables high-throughput co-culture studies of the airway tissue.

Keywords: airway
in vitro
microfabrication
microfluidics
suspended microfluidics
thermoplastics
Advisor: Young, Edmond
Gene Association Studies of Clozapine Response: A Dopamine System Approach

The antipsychotic clozapine (CLZ) is under-utilized due to its life-threatening side-effects despite superior efficacy for treatment-resistant schizophrenia (SCZ). Thus, predictors for response could help inform drug administration decisions. Given the genetic basis for response, we aimed to identify genetic predictors and build a preliminary genetic model for CLZ efficacy. Since CLZâ s targets the DA system, we investigated a DA D2 receptor (DRD2) gene variant implicated in SCZ risk in a recent genome-wide association study. We observed that the A-allele was associated with better CLZ response. We also examined the association between catechol-O-methyltransferase gene (COMT) polymorphism Val158Met and antipsychotic response, observing that Met/Met was associated with greater improvement. Lastly, we developed a genetic model for response, consisting of four polymorphisms from the DRD2, serotonin-6 receptor (5-HT6), brain-derived neurotrophic factor (BDNF), and neurexin-1 genes (NRXN1) (Adjusted R2=52%, sensitivity=70%, specificity=47%). While replication is required, our findings identify several potential genetic predictors of response.

Keywords: Antipsychotics
Clozapine
Personalized Medicine
Pharmocogenetics
Schizophrenia
Treatment Response
Advisor: Kennedy, James L
Feasibility of an Online Cognitive Environmental Enrichment Intervention for Patients with Moderate-to-severe Traumatic Brain Injury

Recent research has documented progressive cognitive and neural decline in the chronic stages of moderate-to-severe traumatic brain injury (TBI). Offsetting this putative neurodegeneration offers a new target for cognitive neurorehabilitation. Cognitive environmental enrichment (C-EE; novel, challenging, and engaging cognitive stimulation) delivered early post-TBI has been shown to buffer against neurodegeneration in humans and animals. Some online "brain games" (which can be accessed by patients regardless of location or mobility restrictions) offer intensive cognitive stimulation that meet the criteria for C-EE. Here, the feasibility of administering a home-based, online "brain game" suite to 11 moderate-to-severe TBI patients who participated in 12 weeks of intensive cognitive training was examined. Modest adherence and attrition, high acceptability of the program, and promising findings on limited-efficacy testing involving neuropsychological outcomes were observed. Online cognitive training is a feasible and potentially efficacious intervention for TBI patients. Means of improving adherence are discussed.

Keywords: Cognitive intervention
Environmental enrichment
Feasibility
Neurodegeneration
Neuropsychology
Traumatic brain injury
Advisor: Green, Robin EA
Oxidative Stress and BDNF as Putative Biomarkers of Cognitive Flexibility in Adolescent Bipolar Disorder

Executive dysfunction is common and impairing in bipolar disorder (BD), and its pathophysiology is poorly understood. Oxidative stress (OS) and brain-derived neurotrophic factor (BDNF) have been implicated in executive deficits of adult BD, but have not been studied in youth. Serum levels of OS and BDNF were measured in 30 BD and 25 healthy control (HC) adolescents. The intra-extra-dimensional (IED) set-shifting task assessed executive function, particularly cognitive flexibility. High and low BDNF subgroups were defined by median split. IED performance was impaired in BD subjects. LPH and BDNF had opposite correlations in BD and control subjects. LPH and IED performance was oppositely correlated between BD and control subjects. These correlations became stronger when parsed by BDNF. LPH and BDNF have an altered interaction in BD that is relevant to executive function. Antioxidant interventions to improve executive function may be warranted, especially when guided by BDNF levels.

Keywords: adolescent
BDNF
Biomarkers
cognition
Oxidative stress
psychiatry
Advisor: Goldstein, Benjamin I
Lanctot, Krista
The Mechanistic Function of the NOD-like Receptor NLRX1 in Apoptosis and Cell Death in the Nervous System

The mitochondrial protein NLRX1 belongs to the family of cytosolic nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs). NLRs respond to invasive pathogens, and danger signals released from dead or dying cells. The function of NLRX1 was previously reported to be in anti-viral immunity, however we propose a non-immune role for this protein in apoptosis. We show here the function of NLRX1 to be inhibitory to extrinsic apoptosis and permissive to intrinsic apoptosis. Furthermore, we validate the previously reported interaction between NLRX1 and sterile-α and TIR motif containing protein 1 (SARM1). SARM1 is expressed in the nervous system, and has a pro-apoptotic function in addition to its role in promoting Wallerian degeneration. We found NLRX1 to have both SARM1-dependent and -independent functions during apoptosis. Furthermore, we test NLRX1 function during Wallerian degeneration following axotomy, and a central nervous system injury model involving ischemic stroke.

Keywords: Apoptosis
Cell Death
NLRX1
SARM1
Stroke
Wallerian Degeneration
Advisor: Philpott, Dana J
Girardin, Stephen E
Phagocytosis of Filamentous Bacteria: Impact of Target Morphology on Phagosomal Maturation

Phagocytosis has been characterized by studies that utilized spherical particles as targets. However, phagocytes encounter targets of a disparate morphology in nature. Particles with filamentous morphology can present a hurdle to phagocytosis. For example, during phagocytosis of long filamentous targets (FTs), the phagocytic cups can take more than 30 minutes to be internalized. During this time, the phagocytic cup is composed of two domains – the actin-rich domain proximal to the membrane and the internal phagocytic cup (PC), which is embedded within the cytoplasm. Here, we present evidence that early endosomal lipid regulator, PI(3)P is recruited to PCs and co-exists with lysosomal protein, LAMP1. Our results indicate that aberrant recruitment of PI(3)P is a consequence of the neutrality of the compartment on which it is maintained, acidification of PCs abrogates PI(3)P recruitment to PCs. Our findings reveal that key aspects of phagosomal maturation are conditioned by the morphology of the target.

Advisor: Terebiznik, Mauricio
Integration of Selectively Transparent and Conducting Photonic Crystals (STCPCs) in Tandem Silicon Photovoltaics

A proof-of-concept integration of the Selectively Transparent and Conducting Photonic Crystal (STCPC) as a spectrally tunable intermediate reflector (IR) is reported for an amorphous-silicon (a-Si:H)/crystalline-silicon heterojunction (c-Si HJ) tandem solar cell. Optical and electrical studies present the simulation, fabrication, and testing of the tandem cells with no IR, Zinc Oxide IR (ZIR), and STCPC IR. The STCPC IR showed current-density (JSC) increases of up to 17.1% over no IR, and 13.2% over the ZIR. A small relative efficiency decrease of 10% in the STCPC case relative to the ZIR case was observed from the lack of optimal interface layers. Additionally, the effect of varying STCPC reflection band centre peak positions (480, 530, 580 and 630 nm) was examined. External quantum efficiency and JSC enhancements were observed in these cases, though these structures require electrical interface optimization to completely avail the benefits of STCPC integration in tandem silicon/other material photovoltaic systems.

Keywords: multi-junction
photonic crystals
photonics
photovoltaics
solar
solar cells
Advisor: Kherani, Nazir P
Women in Jamaican Dancehall: Rethinking Jamaican Dancehall through a Women-Centered Informal Economy Approach.

Some academic discussions that address women who participate in Jamaican Dancehall have taken the position that these women lack morality and agency and have internalized sexist norms (Lake 1996). This is because of the overtly sexual nature of the cultural expression. This research project aimed to expand the conversation concerning these women by investigating how female dancehall dancers, models and auxiliaries (designers, beauticians and vendors) make a living from Dancehall's informal economy. Through empirical evidence, this research will suggest that women who participate in Jamaican dancehall have subjectively and economically benefited from the informal economy that is embedded in dancehall.

Keywords: Dancehall
Economic Mobility
Income Generatig Practices
Informal Economy
Transnational
Women in Jamaican Dancehall
Advisor: Trotz, D. Alissa
Walcott, Rinaldo
Microfluidic Preparation of Air- and Moisture-sensitive Precursor Solutions and Semiconductor Nanocrystals

Syntheses of a wide range of air- and moisture-sensitive chemistries are conducted in dedicated, capital-intensive setups that are not amenable to automation and offer only limited process control and scalability. Here, we demonstrate a compact Schlenk-line-to go (SL2G) platform that overcomes these limitations. Case studies of semiconductor precursor solutions and colloidal nanomaterials are presented. The rapid and reproducible preparation of precursor solutions and NCs is achieved by a microfabricated sparger that promotes rapid mixing and temperature control. We expect the benchtop SL2G platform to enable air- and moisture-sensitive syntheses to be conducted independent of a fume hood or a glovebox and in a manner that is scalable, automatable, and compatible with flow chemistry.

Keywords: air-sensitive techniques
flow chemistry
microfluidics
Schlenk line
semiconductor nanocrystals
Advisor: Guenther, Axel
Epigenetic Study of Plasma Circulating DNA in Prostate Cancer

Malignant cells exhibit epigenetic differences compared to normal cells, which can also be detected in the cell-free circulating DNA (cirDNA) of bodily fluids. DNA modification studies in cirDNA may lead to the development of non-invasive cancer biomarkers. This thesis investigates plasma cirDNA modifications of prostate cancer patients, benign prostate hyperplasia patients, and men without any known prostate disease. A modification-sensitive restriction enzyme approach was used to enrich the modified DNA fractions, which were interrogated on CpG island- and Affymetrix tiling microarrays. Our initial discovery screen identified a number of differentially modified genes and non-coding loci between PCa patients and controls; a subset of candidate loci were verified using bisulfite pyrosequencing. We applied machine-learning techniques to develop a multi-locus biomarker set, which exhibited promising predictive performance in distinguishing cancer patients from unaffected controls. Our results suggest that epigenomics of cirDNA is a promising source for diagnostic non-invasive biomarkers of solid tumors.

Advisor: Petronis, Arturas
A RhoGEF that Promotes Par6-aPKC Pathway Activity for Establishing Epithelial Polarity in Drosophila

Apical-basal polarity is important for the integrity of Drosophila embryonic epithelia. Polarity is established when Cdc42, a Rho GTPase, activates the conserved Par6/atypical protein kinase C (aPKC) complex, and recruits them to the apical domain. However, the RhoGEF that activates Cdc42 in Drosophila is unknown. Through an shRNA screen, I isolated the RhoGEF CG10188 which when knocked down produced similar defects as aPKC mutants. Furthermore, disruption of CG10188 and aPKC together enhanced the defects observed with either single disruption, demonstrating a genetic interaction between the two. However, aPKC localization appears to be independent of CG10188 regulation. Lastly, mammalian proteins that share high sequence identity with CG10188 have been previously shown to activate RhoA, another Rho GTPase, suggesting that CG10188 could be upstream of either Cdc42-Par6-aPKC or Drosophila RhoA (Rho1). Overall, my results suggest that CG10188 is a novel polarity regulator that promotes epithelial development in the Drosophila embryo.

Keywords: Drosophila
Epithelial Polarity
Polarity Protein Complex
Advisor: Harris, Tony
Consumption of Non-cow's Milk and 25-Hydroxyvitamin D Levels in Early Childhood

Non cow’s milk includes goat’s milk and plant-based milk beverages. Vitamin D fortification of non-cow’s milk is voluntary in North America. The effect of non-cow’s milk on serum 25-hydrxovytamin D levels is unclear. Through two studies, I aimed to determine the association between non-cow’s milk consumption (both animal and plant based) and 25-hydroxyvitamin D serum levels in early childhood. Children ages 1-6 years were recruited through the TARGet Kids! practice based research network between 2008 and 2013. Non-cow’s milk consumption, 25-hydroxyvitamin D serum levels and clinically relevant covariates were collected. In study 1, I identified a dose dependent association between higher non-cow’s milk consumption and lower 25-hydroxyvitmian D levels. In study 2, I demonstrated that consumption of plant-based milk beverages was associated with lower 25-hydroxyvitamin D; the magnitude of this association was both smaller and in the opposite direction to the relationship of both cow’s milk and goat’s milk and 25-hydroxyvitamin D.

Keywords: early childhood
Pediatrics
public health policy
TARGet Kids!
vitamin d
Advisor: Maguire, Jonathon L
Creep and Shrinkage of Concrete Exposed to Low Relative Humidity and High Temperature Environments

The long-term behaviour, particularly shrinkage and creep, of concrete exposed to environments in which the relative humidity is low and the temperature is high is uncertain. Most existing creep and shrinkage models impose limits on relative humidity such that they cannot be used when the relative humidity is low. This thesis investigates the ability of creep and shrinkage models, despite the imposed limit on relative humidity, to predict both the overall behaviour of concrete specimens exposed to extreme conditions and the internal behaviour of thick concrete sections exposed to extreme conditions which differ on either side. Results suggest that the limit on relative humidity may be ignored and that model predictions conservatively estimate long-term structural behaviour.

Keywords: concrete
creep
high temperature
internal
low relative humidity
shrinkage
Advisor: Kwon, Oh-Sung
Bentz, Evan C
Biochemical Status of Vitamin D and Related Biomarkers as Predictors of Severe Influenza Infection in Children

Eighty-two influenza-positive children were recruited prospectively from the inpatient units of four Canadian pediatric referral centers. Serum 25-hydroxyvitamin D [25(OH)D] levels were inversely associated with influenza severity (B = -0.43, p-value = 0.03). Participants whose serum 25(OH)D levels fell below 50 nmol/L had significantly higher maximum Composite Severity Index ÂŽ (maxCSI) scores than those with serum levels â Ľ50 nmol/L (medians of 56 vs. 37, p-value = 0.01). Serum LL-37 levels were also found to be inversely associated with maxCSI scores among participants (B = -0.78, p-value = 0.03). Only serum 25(OH)D levels remained a significant predictor of influenza severity when incorporated into a multivariable model controlling for patient sex, age, zBMI, maternal education, vaccination status and influenza type (B = -0.50, SE = 0.20, p-value = 0.04). Results from this study indicate that serum 25(OH)D levels

Keywords: 25(OH)D
Influenza
Pediatrics
Severity
Vitamin D
Advisor: O'Connor, Deborah L
Tran, Dat