VictorJuiz/thesis huggingface dataset:
Directional Shift in Mitochondrial Heteroplasmy
Keywords: G-Quadruplex
Leigh Syndrome
m.10191T>C
Mitochondria
Mitochondrial Disease
mtDNA

Diseases due to mitochondrial DNA (mtDNA) mutations are lethal and few therapeutic options are available. Because these mutations often exist in a state of heteroplasmy, the coexistence of wild-type and mutated mtDNA, strategies that can alter this ratio in favor of wild-type mtDNA (“heteroplasmy shifting”) may be therapeutically useful. We found that the Leigh syndrome (LS)-associated m.10191C variant promotes G-Quadruplex (GQ) formation within local sequence in vitro. The GQ formed at m.10191C differentially impeded the processivity of the mitochondrial DNA polymerase gamma (POLG) in vitro, providing a potential means to favor replication of the wild-type allele. Treatment of patient fibroblasts with GQBA induced alternating mtDNA depletion and repopulation and was effective in shifting heteroplasmy towards the non-pathogenic allele. Following treatment, heteroplasmic m.10191T>C cells had increased in maximal mitochondrial oxygen consumption. We developed a high-throughput assay to screen 23,000 GQBA for preferential binding to m.10191C allele with minimal off-target effects and two compounds were identified with favourable characteristics. We observed that mitochondria in patient cells harbouring pathogenic heteroplasmic mtDNA mutation are hyperfused compared to controls. Fragmenting mitochondria by knock down of fusion genes led to shift in mitochondrial heteroplasmy. This study demonstrates the potential for using small-molecule GQ-binding agents to induce genetic and functional shift in m.10191T>C mutation and mitochondrial fragmentation may have synergistic effects.
Evaluating the Construct of Emotion Differentiation: Methodological Considerations and Extension of Current Theory
Keywords: emotion differentiation
emotion regulation
emotional awareness
emotional complexity

Emotion differentiation is a multifaceted construct, referring to the ability to make fine-grained distinctions between emotional experiences as well as the ability to describe individual emotional experiences with a high degree of nuance and specificity. Studies to date have demonstrated that emotion differentiation is associated with indices of psychological well-being, such that greater emotion differentiation performance is presumed to be adaptive. Theory posits that emotion differentiation functions as a precursor to more successful emotion regulation by providing the experiencer with more precise information to contextualize their emotional experience and respond to it more optimally, but this relationship needs further empirical support. Several other issues persist with the construct as currently operationalized, including: (1) it is unknown how the underlying construct empirically relates to similar constructs in the literature, and if it uniquely relates to psychological well-being incrementally beyond these other constructs; (2) it is unknown if emotion differentiation can be measured via self-report and do such measures correlate with performance-based approaches; and (3) emotion differentiation lacks measures in the context of individual emotional experiences, suggesting the full theoretical construct is not being captured. This research was therefore undertaken with the goal of systematically addressing each of these lingering issues. Results of Study 1 suggested that emotion differentiation is best conceptualized as an aspect of emotional complexity, separate from emotional awareness, and that it does not uniquely relate to psychological well-being after accounting for empirical overlap with awareness. Study 2 results indicated that a coding-based measure of differentiation within individual emotional experiences related to indices of psychopathology but did not relate to emotion differentiation between emotional experiences. All associations between indices of emotion differentiation and psychopathology were accounted for by mean affect intensity. In Study 3, those who were instructed to appraise their emotions with less nuance reported more emotion regulation success following one negative emotion-inducing video, and those from this group who reported high trait emotional awareness reported the greatest emotion regulation success following the other negative video. Collectively these results highlight continuing concerns with emotion differentiation theory and measurement.
Process Development for Quadruple Fortification of Salt
Keywords: Folic Acid
Iodine
Iron
Process Development
Salt Fortification
Vitamin B12

This process was developed to simultaneously deliver iron, iodine, folic acid, and vitamin B12 for holistic prevention of anaemia and other risk factors for prenatal complications in vulnerable populations. Salt was chosen as the ‘vehicle’ for the micronutrients because ‘doses’ of the micronutrients can be predicted. The process was based on a cold forming extrusion-based microencapsulation (for making premix) that ensures that added micronutrients are stable, indistinguishably mixed with salt, do not segregate, and do not cause changes to the sensory characteristics of salt and foods. The dusting of the micronutrient premix with titanium dioxide masked its brown colour while its coating with soy stearin prevented the adverse moisture aided interaction between iron and iodine. The hydrophobic nature and the initial amount of soy stearin used for coating caused the micronutrient premix to float; contamination of TiO2 due to its recycling caused dark spots on the surface premix. Double coating with 5% hydroxypropyl methylcellulose and 5% soy stearin solved the floating problem; coating with a mixture of 15% TiO2 and 10% soy stearin solved both problems. The required pH (≥ 8) for full dissociation of folic acid, its solubility, and stability caused vitamin B12 instability; hence, both micronutrients cannot be added to salt through a solution. In salt, they were lost through oxidative degradation. The coextrusion of folic acid and vitamin B12 with ferrous fumarate (a reducing agent) minimized the oxidative degradation of the micronutrients. The colour masking and coating of the premix ensured that the micronutrients did not affect the colour of the salt. Also, the coextrusion prevented the micronutrients from photodegradation. The salt samples can deliver 50-200% recommended dietary allowances of the micronutrients based on the consumption of 10g of salt per day. The micronutrients were very stable in the salt and met the set target (70% retention after 6-month storage). Over 85% of the micronutrients were retained in salt after 6-month storage, even at 45 oC/60-70% RH. The micronutrients were stable in cooking and did not cause any changes to the sensory properties of the salt or food.
Go With the Microfluidic Flow – and Analyze the Nanoparticle's Journey to the Tumour
Keywords: Cancer
Endothelial Cells
Microfluidics
Nanotechnology
Organoid
Tumour Vasculature

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.
Borel Chain Conditions
Keywords: Borel hypergraphs
Borel posets
chain condition
descriptive combinatorics
hypergraphs
partially ordered sets

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.
The Role of the Extracellular Matrix Microenvironment in Regulating Aortic Valve Cell Phenotypes
Keywords: 3D Acellular Tissue
Aortic valve disease
Aortic Valve Lesion
Gene Expression
Micro-mechanical Properties
Optimization

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.
The Politics of Large-scale Land Acquisitions: State Support, Community Responses, and Variations in Corporate Land Control in Senegal
Keywords: Agribusiness
Corporate land control
Large-scale land acquisitions
Senegal
Social movements
States in Africa

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.
Preferences for the Role in Making Treatment Decisions: A Comparison between Patients and Patient Advocates in the Neuroendocrine Cancer Population
Keywords: Decision Making
Health Policy
Patient Engagement
Person-Centred Care
Problem Solving
Trust

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.
Surgical Treatment of Thoracoabdominal Aortic Aneurysms: Endovascular versus Open Approach
Keywords: Aneurysm
Surgery
Thoracoabdominal

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
A Performance Guide to Tan Dun's Elegy: Snow in June
Keywords: Cello Concerto
Chinese New Wave
Chou Wen-Chung
Elegy: Snow in June
Performance Guide
Tan Dun

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.
Operant Conditioning of Single Neuron Activity in Brain-Machine Interfaces
Keywords: brain-machine interfaces
extrinsic factors
intrinsic factors
neuron subtype
neuron type
operant conditioning

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.