VictorJuiz/thesis huggingface dataset:
Go With the Microfluidic Flow – and Analyze the Nanoparticle's Journey to the Tumour

Traditional chemotherapy for cancer treatment often elicits dangerous side-effects and limits the dose that can be administered to patients. In order to alleviate these side-effects, researchers have turned to using nanoparticles to deliver drugs specifically to tumour sites. However, nanoparticles encounter many biological obstacles that prevent them from accumulating efficiently at the tumour sites, and these obstacles are difficult to characterize using animal models. In my thesis, I develop microfluidic tools to examine these obstacles. First, it is difficult to examine how far nanoparticles infiltrate into solid tumours because light cannot enter the tumour. My first project was to design a microfluidic device that renders microscale tissues transparent, so that nanoparticle infiltration into the tumours can be quantified by microscopy. Second, nanoparticles are usually injected into the bloodstream to treat tumours, and will be subject to the fluid dynamic effects of blood flow. These effects impact nanoparticle accumulation in the tumour. In my second project, I engineered an artificial blood vessel inside a microfluidic chip, allowing researchers to control the flow rate of the nanoparticles while they interact with the cells of a blood vessel. From this project, we learned that more nanoparticles travel through the blood vessel when the flow rate is decreased. Lastly, the flow rate of blood is heavily influenced by the shape of the blood vessel network. In tumours, the blood vessel network is chaotic and unpredictable, making the blood flow rate uncontrollable. In my third project, I produced microfluidic devices that contain micro-channels in the shape of tumour blood vessel networks. These devices are fabricated from 3D images of tumours from animal models, and are real-life replicas that can be reproducibly and predictably produced. It is possible to use these devices to examine how the shape of the tumour vasculature affects the blood flow rate, and therefore the accumulation of nanoparticles at the tumour. In summary, my thesis produced three microfluidic systems that enable researchers to examine three biological obstacles that prevent nanoparticles from being used effectively for anti-cancer treatment.

Keywords: Cancer
Endothelial Cells
Microfluidics
Nanotechnology
Organoid
Tumour Vasculature
Advisor: Chan, Warren C.W.
Rocheleau, Jonathan V.
Borel Chain Conditions

The subject matter of this Thesis is an instance of the Chain Condition Method of coarse classification of Boolean algebras and partially ordered sets. This method has played an important role in the measure theory, the theory of forcing, and the theory of Martin type axioms. First, We give a fine analyze on a class of hypergraphs that generalizes G0, the central object of the G0-dichotomy. We focus on the posets that are Borel definable in Polish spaces and investigate the connections between the chain condition method and the chromatic numbers, a classification scheme for graphs. We then introduce Borel version of some classical chain condition and show that the Borel poset T(πQ), the Borel example Todorcevic used to distinguish σ-finite chain condition and σ-bounded chain condition, cannot be decomposed into countably many Borel pieces witnessing the σ-finite chain condition, despite the fact that the non-Borel such partition exists. Starting from there, we use aforementioned hypergraphs to construct a number of examples of Borel posets of the form D(G) that the new hierarchy of Borel chain conditions is proper.

Keywords: Borel hypergraphs
Borel posets
chain condition
descriptive combinatorics
hypergraphs
partially ordered sets
Advisor: Todorcevic, Stevo
The Role of the Extracellular Matrix Microenvironment in Regulating Aortic Valve Cell Phenotypes

Calcific aortic valve disease (CAVD) is an active, cell-mediated pathology associated with significant cardiovascular morbidity but with no current pharmacologic treatments. In late CAVD, the aortic valve (AV) leaflets become fibrotic and calcified, but early CAVD is characterized by proteoglycan-rich subendothelial lesions in the fibrosa layer of the leaflets. Valve interstitial cells (VICs) in these early lesions express higher levels of genes associated with bone and cartilage formation in situ, motivating the hypothesis that the lesion microenvironment promotes VIC pathological gene expression. VIC pathological differentiation has been shown to be affected by both ECM mechanics and composition, but the relevance of these in vitro studies to the lesion microenvironment was unknown. I first determined if early AV lesions have local mechanical properties that are distinct from those normal valve tissue. A custom microindentation device was developed and validated. For the first time, I showed that the compressive moduli of early lesions were ~2.4 fold softer than healthy non-lesion regions. As a top-down approach to test the effect of the lesion microenvironment on VIC responses, I then established a novel ex vivo decellularized valve model of normal valve ECM and early CAVD, defining decellularization conditions that maximally removed cells and preserved ECM microenvironment. I then applied the model to investigate the influence of normal versus diseased ECM on VIC phenotypic expression. Several genes involved in osteogenic (e.g., RUNX2, MSX2 and SPP1) and chondrongenic (e.g., ACAN, HYAL2 and CHSY1) processes were upregulated in naïve VICs grown in lesion microenvironments compared to non-lesion fibrosa areas. Inflammatory and ECM related genes were differentially expressed between lesion and non-lesion fibrosa. These in vitro expression patterns match lesion vs. non-lesion gene expression profiles measured in vivo, supporting the validity of my decellularized tissue model and a role for the ECM in driving VIC gene expression associated with pathologic differentiation. The significant findings of this thesis provide novel insights into the role the ECM plays in regulating native valve (dys)function. This thesis also contributes new tools and knowledge to disease modeling research, with broad applications towards better understanding the role of the ECM in health and disease.

Keywords: 3D Acellular Tissue
Aortic valve disease
Aortic Valve Lesion
Gene Expression
Micro-mechanical Properties
Optimization
Advisor: Simmons, Craig A.
The Politics of Large-scale Land Acquisitions: State Support, Community Responses, and Variations in Corporate Land Control in Senegal

Over the last two decades, Senegal has experienced an unprecedented wave of large-scale land acquisitions. Despite the apparent surge, however, many of the reported spectacular land deals never materialized, have been facing major operational difficulties, or collapsed altogether. This observation was the starting point of this doctoral investigation, which asked: What factors explain the variations in the capacity of external investors to acquire and maintain control over land for the conduct of their agribusiness projects in Senegal? It is the primary contention of this dissertation that central state responses to investors critically shape corporate land acquisition and control. The governments of both Presidents Abdoulaye Wade (in power from 2000 to 2012) and Macky Sall (in power since 2012) have encouraged private investments in the agricultural sector and extended help to facilitate corporate land acquisition and control. But, contrary to expectations, state support for seemingly powerful investors has not been systematic and steady. In particular, the government has to a large extent been responsive to social opposition and has ended controversial land projects even though they squarely aligned with government priorities. If, among the myriad actors involved in land deals in Senegal, the central government has the greatest capacity to guarantee corporate land control, state behaviour is itself moulded by social interactions and political struggles that take place within interlocking arenas of power at the local, regional, national, and international levels. The combination of actors’ normative positions, objectives, resources, and strategies define their bargaining power, that is their capacity to affect land control outcomes. Based on a documentary analysis of private collections and public materials, 309 in-depth qualitative interviews with key actors, and sustained field observations in Dakar and the countryside, this dissertation advances an original analytical framework that takes into consideration the multilayered configurations of power shaping corporate land control. By grasping how external investors handle their insertion in complex arenas of power, this dissertation reframes our current understanding of the so-called “scramble for land,” and illustrates that Africa is not as amenable to corporate takeover as usually pictured by both proponents and critics of industrial agriculture.

Keywords: Agribusiness
Corporate land control
Large-scale land acquisitions
Senegal
Social movements
States in Africa
Advisor: Teichman, Judith
Preferences for the Role in Making Treatment Decisions: A Comparison between Patients and Patient Advocates in the Neuroendocrine Cancer Population

Background: Patient engagement has become a common focus for healthcare organizations in the last decade and is a priority in Canadian healthcare policies and research strategies. Objectives: The objective of this thesis was 1) to examine the association between the preferred role in treatment decisions that adult patients and patient advocates with a rare cancer, neuroendocrine (NETs), wish to play in their care, and 2) to test the hypothesized relationship with ehealth literacy, trust in physician, information seeking behaviours and sociodemographic variables within and across both groups (patients and patient advocates). Design: A cross-sectional survey design was used to measure preferred roles in problem solving and decision-making. Methods: Preferred roles were measured across two health vignettes: ‘current health condition’ and ‘chest pain’. Bivariate analysis was conducted to determine associations between socio-demographic variables and preferences for problem solving (PS) and decision-making (DM). PS is preference-independent and relates to tasks in determining the nature of the problem, structuring the decision tree and determining probabilities, such as who should determine the risks and benefits of different treatment options. Conversely, DM tasks relate to determining patient preferences (including risk attitude) and making the decision, considering what matters to you as an individual. Associations between the eHealth literacy score, Trust-in-Physician score, information seeking behaviour and continuous socio-demographic variables were calculated. Results: There were significant differences between preferred roles and trust in the physician and whether a participant was a patient or a patient advocate. There are three main categories of preferred roles: passive, shared and autonomous. The results of this research showed that most patients preferred a passive or shared-leaning passive role, had a high level of perceived health information literacy, and had high levels of trust in their physician. Patient advocates more often preferred a shared role, had a lower trust in their physician and lower perceived ehealth literacy compared to patients. Results of the binary logistic regression showed that trust in the physician predicted respondents of both groups’ preferred roles for both vignettes; chest pain and neuroendocrine treatment decisions. Conclusion: This study provides new knowledge that advances the understanding of the association of preferred roles of problem solving and decision-making for patients as well as patient advocates with a rare cancer.

Keywords: Decision Making
Health Policy
Patient Engagement
Person-Centred Care
Problem Solving
Trust
Advisor: Deber, Raisa
Longo, Christopher J
Surgical Treatment of Thoracoabdominal Aortic Aneurysms: Endovascular versus Open Approach

Introduction: Open thoracoabdominal aortic aneurysm (TAAA) repair is being challenged by less invasive endovascular repair. A large proportion of patients with TAAA could undergo repair via either an endovascular or open approach, and in most cases there is clinical equipoise as to which strategy leads to better short and long-term outcomes. Methods: Systematic review and meta-analysis of studies comparing endovascular versus open TAAA repair, and description of contemporary results of studies reporting either approach. Validation of administrative codes to identify endovascular and open TAAA repair, with acceptable positive predictive value (PPV) (> 0.90). Population-based study comparing the outcomes of endovascular versus open TAAA repair in Ontario, Canada, from 2006-2017. Results: The comparative data describing the outcomes of endovascular versus open TAAA repair was limited (8 studies), with substantial risk of bias. There is a lack of standardization in reporting TAAA characteristics and outcomes in the literature. Pooled analysis of unmatched observational studies revealed a mortality benefit for endovascular repair [relative risk (RR) 0.63 (95% CI:0.45-0.87)], although there was no difference in mortality or complications in the two papers that accounted for baseline differences. PPV for the single endovascular TAAA repair code in Ontario administrative databases was 0.90 (0.78, 0.97). Combination of ten administrative codes from two databases for open TAAA repair rendered a PPV of 0.98 (0.90, 1.00). In the population-based study, endovascular repairs now comprise over 50% of total repairs in Ontario. Open repair was associated with a higher incidence of in-hospital death (17.4% vs 10.8%, p=0.04), life-altering events (26.1% vs 17.4%, p=0.02), discharge to re-habilitation facilities (18.7% vs 10.0%, p=0.02), and longer length of stay (12 [7-21] vs 6 [3-13] days, p

Keywords: Aneurysm
Surgery
Thoracoabdominal
Advisor: Ouzounian, Maral
Lindsay, Thomas F
A Performance Guide to Tan Dun's Elegy: Snow in June

In 1991, Tan Dun composed a work titled Elegy: Snow in June in the form of a concerto for solo cello with percussion quartet. His composition is positioned at the junction of legend (The Injustices of Dou E), contemporary music, and traditional Chinese cultural references. By using traditional Chinese musical materials and a combination of Western and Chinese instruments in Snow in June, Tan created a successful work thanks to his strategic incorporation of varied musical ideas and broader intercultural influences. The thesis includes an examination of the compositional techniques and strategies, information about Chinese traditional theatre, and interviews with performers who have championed this composition. It constructs a performance guide for Elegy: Snow in June by providing information about how to approach the cello when performing works that combine Western musical notation with musical ideas derived from traditional Chinese music, and also addresses the practical setup of percussion quartet, balance issues and appropriate instrument selection.

Keywords: Cello Concerto
Chinese New Wave
Chou Wen-Chung
Elegy: Snow in June
Performance Guide
Tan Dun
Advisor: Huang, Aiyun
Elliott, Robin
Operant Conditioning of Single Neuron Activity in Brain-Machine Interfaces

Invasive brain-machine interfaces (BMIs) have the potential to restore lost motor function due to paralysis. However, successful operation of BMIs depends on the extent to which neural activity can be volitionally modulated. Operant conditioning of single cortical neurons induces the rapid acquisition of arbitrary associations between machines and neural activity. In this thesis, I aimed at exploring intrinsic and extrinsic factors that influence single neuron behavior in a BMI, guided by operant conditioning in a rat model. Extracellularly recorded single neuron activity, from layer V of the motor cortex, was conditioned in BMI tasks designed to up-regulate instantaneous or smoothed firing rates. In the first two studies (Chapters 3 4), the neuron type was investigated as an intrinsic factor. Differences were found in the neuron-type-specific utility (defined as the degree of activity up-regulation), and in the neuron-type-specific responses in the activity leading to a reward. Next, I investigated the type of BMI task as an extrinsic factor (Chapter 5). Two tasks were compared: (i) a threshold-based task, in which firing rates surpassed a threshold, and (ii) a graded-activation task, where firing rates were maintained within a narrow window of activation. Single neuron activity was selectively up-regulated in the threshold-based task, while the graded activation task involved activation of neurons in the local network. This thesis demonstrates that intrinsic and extrinsic factors have an influence in the behavior of single neurons, and that these factors might inform the design of BMIs.

Keywords: brain-machine interfaces
extrinsic factors
intrinsic factors
neuron subtype
neuron type
operant conditioning
Advisor: Popovic, Milos R.
Marquez-Chin, Cesar
Long Non-Coding RNAs in the Endothelial Cell Response to Shear Stress

Endothelial cells (EC) act as professional sensors of shear stress, the frictional force of blood flow. In the absence of laminar (healthy) blood flow, ECs undergo changes in gene expression of protein-coding genes that can predispose the blood vessel to cardiovascular diseases (CVD), such as atherosclerosis and aneurysms. However, whether shear stress influences the non-coding transcriptome, particularly for long non-coding RNAs (lncRNAs), is not well understood. LncRNAs are defined as transcripts >200 nucleotides lacking protein-coding potential that are increasingly recognized as important effectors of gene regulation. We have identified an EC-enriched lncRNA, termed STEEL, that is upregulated by the absence of laminar flow to promote angiogenesis and vessel maturation both in vitro and in vivo. To comprehensively study the effects of shear stress on EC lncRNAs, five independent HUVEC lines were subjected to static (no flow) or laminar flow (10 dynes/cm2, 48 hours) using a parallel-plate flow chamber. RNA was analyzed using a microarray to profile 30,586 lncRNAs. In brief, 394 (3.2%) and 324 (2.7%) lncRNAs were upregulated or downregulated, respectively (≥2 fold vs. static, p

Keywords: atherosclerosis
cardiovascular
endothelial cell
epigenetics
hemodynamics
long non-coding RNA
Advisor: Marsden, Philip A
Identification of New Regulators of the Pollen-pistil Dalogue in Arabidopsis thaliana

In flowering plants, continuous cell-to-cell communication between the male pollen grain/growing pollen tube and the female pistil is required for successful sexual reproduction. In Arabidopsis thaliana, the later stages of this dialogue are mediated by several peptide ligands and receptor kinases that guide pollen tubes to the ovules for the release of sperm cells. Despite a detailed understanding of these processes, a key gap remains on the nature of the regulators that function at the earlier stages. This thesis describes the identification and characterization of two groups of A. thaliana receptor-like kinases, the LRR-VIII-2 RLK subgroup and the SERKs, that are implicated in this process. These receptor-like kinases were observed to function in the female reproductive tract to regulate the compatible pollen grains and early pollen tube growth, both essential steps for the downstream processes leading to fertilization. Multiple A. thaliana LRR-VIII-2 RLK and SERK knockout mutant combinations were created, and several phenotypes were observed such as reduced wild-type pollen hydration and reduced pollen tube travel distances. As these mutant pistils displayed a wild-type morphology, the observed altered responses of the wild-type pollen are proposed to result from the loss of these receptor-like kinases leading to an impaired pollen-pistil dialogue at these early stages. Furthermore, using pollen from related Brassicaceae species, we also discovered that these receptor-like kinases are required in the female reproductive tract to establish a reproductive barrier to interspecies pollen. Thus, we propose that the LRR-VIII-2 RLKs and the SERKs play a dual role in the preferential selection and promotion of intraspecies pollen over interspecific pollen.

Advisor: Goring, Daphne R
Characterization of the Complex Permittivity of Planetary Regolith Analogue Materials

Radar has long been used as a tool for remote sensing of planetary bodies. Orbital radar systems are or have been in orbit around the Moon, Mars, and Venus, while ground-penetrating radar systems are or have been used on the Moon. Despite an abundance of radar data, a lack of information on the fundamental electromagnetic properties of the surface and near-subsurface materials of these bodies precludes detailed quantitative analysis. This includes determining the precise depth of radar-detected sub-surface features as well as refining estimates of abundance of subsurface materials, such as the mineral ilmenite. Although laboratory measurements have been made in the past in order to quantify electromagnetic properties of lunar and martian materials, these measurements provide a limited view of the parameter space of influence on these electromagnetic properties. This thesis develops a full methodology to measure the complex permittivity of planetary regolith analogue materials in vacuum over a broad range of frequencies. These methods are first demonstrated with measurements of analogue regolith materials appropriate for carbonaceous asteroids: individual and mixed components of a regolith simulant based on CI meteorite mineralogy. These measurements are the first to investigate the effect of carbonaceous material on the complex permittivity of asteroid regolith analogues and they provide new constraints on the attenuation of radar in granular carbonaceous materials. This thesis also develops a Bayesian Markov Chain Monto Carlo (MCMC) -based parameter estimation technique to determine the frequency-dependent complex electric permittivity and magnetic permeability. The technique uses a generalized dielectric response (GDR) model to simultaneously determine the complex permittivity and permeability from measured scattering parameters. The technique is able to accurately determine both of these electromagnetic parameters for low-loss, high-loss, and magnetic materials. Finally, measurements of samples with systematically varying amounts of ilmenite are presented along with Bayesian model fits using a one-pole Cole-Cole model. These results represent the first systematic laboratory measurements investigating the effect of ilmenite on radar attenuation. They demonstrate the significant frequency-dependent effect of ilmenite content on signal attenuation and show promise for the application of dielectric spectroscopy, or the identification of materials based on the physical parameters of a GDR model.

Keywords: Bayesian fitting
complex permeability
complex permittivity
radar
regolith
Advisor: Ghent, Rebecca R.