VictorJuiz/thesis huggingface dataset:
Circulating Pro-vascular Progenitor Cell Content in Type 2 Diabetes
Keywords: Aldehyde Dehydrogenase
Diabetes
Inflammation
Ischemia
Progenitor Cells
Revascularization

The chronic inflammation and oxidative stress associated with established type 2 diabetes (T2D) remains a major proponent of ischemic cardiovascular complications. Importantly, the bone marrow (BM) microenvironment plagued by hyperglycemia and oxidative stress hinders pro-vascular progenitor cells from self-renewing and undergoing pro-vascular cell differentiation through a process called “regenerative cell exhaustion”. This phenotype ultimately reduces progenitor cells’ ability to migrate to areas of ischemia and aid in the process of revascularization. Using multi-parametric flow cytometry, we hypothesized that this cellular phenotype, characterized by reduced migration and pro-angiogenic progenitor cell content, could be detected within the peripheral blood of individuals with established T2D. Patients with T2D displayed increased pro-inflammatory granulocyte precursors and reduced circulating progenitor cells with a pro-angiogenic phenotype. This translational work may create the foundation for diagnostic tests that monitor the capacity for revascularization and the efficacy of cellular therapies through a minimally invasive procedure.
Rethinking the Assessment of Hyperbilirubinemia in Preterm Infants
Keywords: bilirubin
hyperbilirubinemia
jaundice
neonatology
quantile regression

Preterm infants born at 240/7 to 356/7 weeks’ gestation are at greater risk of developing acute bilirubin encephalopathy (ABE) and chronic bilirubin encephalopathy (CBE). However, guidelines for the assessment of hyperbilirubinemia are consensus-based, and systematically derived pre-treatment total serum bilirubin (TSB) percentiles are lacking for preterm infants. Preterm infants who undergo repeat TSB testing are subjected to greater stress, pain, and risk of anemia. To address the aforementioned issues, two multi-site retrospective (Study 1 and 2), and one multi-site prospective (Study 3), cohort studies were conducted at three neonatal intensive care units (NICUs) in Ontario. Study 1 generated pre-treatment TSB percentile levels among infants born at 290/7 to 356/7 weeks’ gestation, using quantile regression. Study 2 generated pre-phototherapy TSB percentiles levels at 24 hours of age among infants born at 240/7 to 286/7 weeks’ gestation and contrasted those pre-phototherapy TSB percentiles with existing consensus-based thresholds produced by Maisels. Study 3 investigated the agreement between transcutaneous bilirubin (TcB) and TSB measurements among preterm infants born at 240/7 to 356/7 weeks, overall, by receipt of phototherapy, by anatomical site of measurement and by self-reported maternal ethnicity. Study 1 produced hour-specific pre-treatment TSB levels at the 40th, 75th and 95th percentiles, with corresponding curves by gestational week at birth. Study 2 observed considerably higher statistically derived pre-phototherapy TSB percentile levels at 24 hours of age at the 75th and 95th percentile than Maisels’ consensus-based TSB thresholds. Study 3 observed higher agreement between TcB and TSB values among preterm infants born at 330/7 to 356/7 weeks’ gestation, prior to phototherapy, whether measured at the forehead or sternum. TcB-TSB agreement was not impacted by ethnicity. The results of this thesis provide new information about bilirubin measurement in preterm infants. Experts and health policy makers may choose to use these data to inform evidence-based guidelines in the assessment (and management) of hyperbilirubinemia in preterm infants.
Metallic NanoPorous Materials, from Design to Degradation
Keywords: coarsening
dealloying
electrocatalysis
electrochemistry
nanoporous copper
nanoporous gold

From (bio)sensing to self-powered wearable electronics, nanomaterials have showed great potentials in empowering the march towards sustainability. The theory, synthesis, characterization, and degradation of metallic nanoporous materials, of particular nanoporous gold, due to its versatility and biocompatibility, and nanoporous copper, due to its extraordinary catalytic and self-sanitizing properties, are discussed. Nanoporous gold was designed and synthesized by electrochemical dealloying from lean noble alloys (silver-gold(-platinum)) with the minimum gold content theoretically sufficient for the development of a fully gold covered nanoporous morphology. Advanced characterization techniques, such as atom probe tomography, were employed to obtain a near atomic-scale resolution of the nanoporous morphology developed from Ag95Au5, the lowest gold content precursor to date. The capabilities and drawbacks of atom probe tomography in characterizing heterogeneous nanomaterials were explored. A non-destructive and inexpensive electrochemical characterization technique was developed to probe the chemistry of the entire surface of such tortuous morphology. Via sulfide selective adsorption on silver, the surface chemistry of nanoporous gold was characterized with a precision of approximately 2 atomic % silver coverage on the outermost monolayer. Mechanical integrity of nanoporous layers developed from lean noble alloys was investigated using a combination of ex situ and in situ microscopy, as well as image processing algorithms. Despite speculations in the literature, capillary stresses during drying of the nanoporous samples was found to have no correlation with crack formation within the dealloyed films. Cracking within the nanoporous layers was analyzed by obtaining crystallographic information from cross-sections of the dealloyed samples. Coarsening behavior of nanoporous gold samples developed from various noble precursors was also studied in different media for long exposure times (up to a few months). Alloying with elements with low surface diffusion coefficients (e.g., platinum) was found to decrease the post-porosity coarsening rate, as also demonstrated in several previous investigations. However, under anodic polarization, platinum containing samples exhibited almost identical coarsening behavior to that of dealloyed binary silver-gold samples. Lastly, the applications of nanoporous copper developed via (electro)chemical techniques in self-sanitizing and catalytic electroreduction of CO2 were reviewed. Additionally, investigations were performed to synthesize nanoporous copper via guided dezincification of brass, a prevalent and inexpensive copper alloy.
Architecting Enterprise Capabilities using a Socio-technical Modeling Framework
Keywords: Conceptual Modeling
Dynamic Capability
Enterprise Modeling
Requirements Engineering
Software Architecture

Information systems and software design are at the center of enterprise strategies as organizations face rapid changes in a global environment. Information systems and digital experiences nowadays play a prominent role in enterprise competitiveness. To this end, researchers and practitioners have built on the concept of capability to analyze what a business can and should do to fulfill its strategic trajectories and design information systems. This research builds on the notion of capability to enable co-design of software and business by representing and analyzing evolution strategies while considering the organization's social and technical needs.The thesis presents research on the development, demonstration, and evaluation of a conceptual modeling framework named ArchCap. It consists of meta-models, methods, guidelines, instantiations, and analysis techniques. An agent-oriented modeling paradigm is adopted to capture social and technical aspects of decisions with the ability to analyze and cater for enterprise-specific characteristics. ArchCap includes a conceptual foundation layer including meta-models, modeling rules, and guidelines to explicate (1) why a capability is needed, (2) how it is achieved, (3) how it fits within the organizational and social setting of the enterprise, and (4) what relationships are required for its success. The analysis layer of ArchCap presents techniques to perform (1) qualitative evaluation, (2) capture different kinds of capability choices, and (3) identify flexibility needs and possible causes of inflexibilities. These components build on research and theories in strategic management and systems thinking to ensure any design can adapt to changing conditions and continuously evolving strategies. The process layer of ArchCap provides a set of repeatable instructions, guidelines, and techniques to enable requirements engineers to leverage the framework. The thesis demonstrates the framework's usability and its research artifacts through its instantiations and two empirical case studies. The success of using the concept of capability and the integrative role of the proposed modeling framework in depicting social and technical requirements were at the center of the empirical research. The analysis techniques of ArchCap were successful in evaluating a particular strategy (consisting of many capability alternatives) and informed decision-makers in these organizations.
An Anti-cytokine Agent for Anhedonia: Investigating the Immune-inflammatory System as a Therapeutic Target for Dimensional Disturbances in Mood Disorders
Keywords: biomarkers
Bipolar Disorder
Depression
Machine learning
Mood Disorders
psychiatry

Patients with depression are conventionally treated with the assumption that a treatment will be broadly effective across multiple dimensions. However, depression is a heterogeneous clinical syndrome that is subserved by multiple convergent and divergent disease processes. Data-driven and ecologically valid phenotypes of phenomenology are needed to parse the heterogenous etiology of depression. Moreover, mechanism-of-action studies should target domain-based pathology with mechanistically plausible treatments and aim to inform disease models.The thesis herein investigated the immune system as a putative therapeutic target for anhedonia, a transdiagnostic, yet specific, and clinically relevant symptom dimension. Anhedonia represents a disturbance in reward- and motivation-related neurobiological processes and is characterized by a diminished ability to enjoy previously enjoyable activities. Brain circuits, nodes, and networks, as well as cellular and molecular pathways (eg dopaminergic transmission, excitotoxicity, synaptic plasticity), subserving anhedonia are preferentially affected by inflammatory processes. Hitherto, no curative treatments have been identified or developed for the treatment of anhedonia. Infliximab, an anti-inflammatory agent that specifically targets tumour necrosis factor-α signalling, reduced anhedonic symptoms in a randomized, double-blinded, placebo-controlled clinical trial. Furthermore, we identified a data-driven inflammatory biotype of adults with bipolar depression who were more likely to derive anti-anhedonic benefit from infliximab. We provide a framework for conceptualizing the therapeutic and mechanistic relevance of the TNF-α signalling pathways in the treatment of anhedonia. Taken together, our findings instantiate the relevance of inflammatory processes and the immune system in the phenomenology and etiology of mood disorders and provide the impetus to develop scalable treatments targeting the immune system to mitigate transdiagnostic, dimensional disturbances (eg anhedonia). A domain-based approach to drug discovery and development, informed by an understanding of disease processes, is needed to target brain-based pathology. Future studies investigating viable anti-anhedonic treatment avenues should demonstrate target engagement in neural systems subserving reward learning and valuation (eg cognition, habit formation), as well as reward-motivated behaviours (eg seeking, consummatory).
Gravitational Wave Echoes: Theory and Application
Keywords: black holes
echoes
gravity
quantum

Black hole mimickers may compose some of what is assumed as the black hole population, and multiple groups have claimed evidence for this in the form of gravitational wave echoes. This thesis elaborates on work by the author and collaborators, detailing echo theory and discussing hints of echoes in gravitational wave data from the LIGO observatory.Echoes from a variety of exotic compact objects are compared, and the effects of spin are investigated. The most characteristic feature of echoes, a series of spectral resonances, is exploited to look for this structure in LIGO data via windowing methods. These resonances are modulated by an initial-condition-dependent source integral, and it is shown that echo features traditionally assumed to be known may be altered by generic production mechanisms. The complete modulation in all variables is calculated, and the impact on echoes is displayed. An analytical method is constructed to test asymptotic radial perturbations. Quantum quadratic gravity is a theory capable of producing echoes, and it can be made renormalizable with ultraviolet completions. It may also satisfy the optical theorem under certain conditions, and these are reviewed and further explored through two subjects: the physical particle spectrum and the complex prescription of propagators. Required conditions for unitarity are defined along with their consequences, and the consistency of the theory is tested against these. The search for echoes is then continued in a recently detected gravitational wave event, GW190521, by employing the latest developments in echo theory. Combining advancements in physical boundary conditions, numerical relativity, and complex representation of the echo spectrum, a model is built to seek for physically motivated echoes across background parameters of mass, spin, and geometry. The search is done over Monte Carlo chains distributed according to background parameter probabilities, with significance assessed by signal to noise ratios and statistical analysis. Potential echo detections in the LIGO events GW151226, GW170104, GW170608, GW170814, and GW170817 are presented with false alarm rates of 1 in 700 or less using the older windowing methods. The latest model is employed to find a false alarm rate of 1 in 50 in GW190521.
Teachers' Use of Discourse to Promote Student Learning in Grade 7 and 8 Mathematics
Keywords: adolescent teaching
classroom environment
cooperative learning
mathematical discourse
teacher education
teacher knowledge

The study investigates how teachers use math discourse in grade 7 and 8 math classrooms. Teaching strategies that use student interaction combine with the natural desire to communicate with teaching. The way teachers interact with their students can increase or decrease their students’ level of participation and engagement and eventual learning of mathematics. The study uses a multiple-case methodology and involves four participants. Data were collected from each participant using two semi structured interviews, two observation sessions, publicly maintained websites and using the researcher’s journal. Each case was analysed separately for major themes and then a cross case analysis was conducted to find similarities and commonalities among the cases. The five major findings of the study are: (1) teachers prepare their students to work in groups of three to four students by doing several activities prior to start engaging them in discourse; (2) teachers nurture a conducive classroom learning environment prior to engaging students in discourse; (3) teachers with good knowledge of mathematics, the curriculum, pedagogical practices, and with extensive teaching experience tend to have more success with using discourse to promote student learning; (4) teachers use focused questioning to help students during math lessons; and (5) teachers improve the level of students participation by using several strategies.
Contextualizing Medicine and its Roles in Seventeenth-century Tibet
Keywords: History of Medicine
History of Tibetan Medicine
Tibet
Tibetan Medicine

This dissertation examines Tibetan medicine and its roles in Tibetan politics and culture throughout history with a focus on the seventeenth-century and the reign of the Fifth Dalai Lama (1617-1682) and his last regent, Desi Sanggyé Gyatso (1653-1705). It explores the role that their patronage of medical institutions, scholarship, and practice played in legitimizing the rule of their new regime and in helping to establish Lhasa as the capital of Tibet. It critically examines how modern scholars have approached the study of Tibetan medical history through a comparative approach with European medical history, arguing that applying ideas and periodizations from the latter onto the former is methodologically unsound. It suggests alternative approaches to the study of Tibetan medical history, including different ways to engage with Tibetan historiography and how we might begin to think about the roles of non-human actors, such as deities, in Tibetan history and medicine.
Temporal Gait Asymmetry: The Relationship of Rhythm Abilities, Perception of Performance, and Responsiveness to Rhythmic Auditory Stimulation
Keywords: asymmetry
gait
perception
rhythm
stroke

A promising intervention to target persistent post-stroke temporal gait asymmetry (TGA) is rhythmic auditory stimulation (RAS). Response to this intervention likely depends on the influence of many patient-related factors. This thesis examined the influence of two such factors on the relationship between TGA and the immediate response to RAS: rhythm ability and perception of gait performance. This thesis is comprised of four studies that investigated perception of an induced TGA in healthy adults, the effect of rhythm ability on the response to RAS with an induced TGA and with post-stroke TGA, and the influence of RAS on TGA perception. A unilateral load induces TGA in neurotypical adults, however accurately perceiving this asymmetry may be a difficult task, as nearly half of participants incorrectly perceive the direction of their asymmetry (study 1). Conversely, people with stroke are mostly accurate at detecting the presence and direction of their TGA (study 4). Both healthy adults and individuals with stroke improve TGA regardless of rhythm ability (study 2 3). Healthy adults with strong rhythm ability demonstrate greater step synchronization to the beat than those with poor ability, though this did not affect the response to RAS (study 2). Some individuals with stroke who worsen TGA with RAS have significantly poorer rhythm ability (study 3). For both healthy adults and people with stroke, walking to a metronome reduces the ability to detect the presence of TGA (study 4). This thesis presents new evidence for the relationship between rhythm abilities, the perception of TGA, and the responsiveness of TGA to RAS. Since some individuals with poor rhythm ability worsen TGA with RAS, clinicians may consider assessing individual rhythm ability when using rhythm-based treatments. The disparate ability to accurately perceive TGA among study participants demonstrates the importance to provide augmented feedback in therapy for interventions that rely on the perception of performance. Future work should explore the influence of rhythm ability on the response of TGA to other auditory stimuli (e.g., music) or the effect of rhythm ability on the response to a RAS intervention and consider alternate approaches to assess the perception of gait performance.
Essays on International Trade and Development
Keywords: Growth
Input-Output Linkages
International trade
Knowledge Diffusion
Misallocation

This thesis contains three papers examining topics related to international trade, growth, and development. In chapter 1, I examine the role of buyer-seller relationships on the global platform for the transfer of knowledge across borders, wherein firms can learn about products produced by each other in a transaction. I find that an exogeneous increase in plants’ access to foreign downstream knowledge through exports increases the likelihood that they produce new downstream products. I then build a model of international trade, knowledge spillovers, and growth to analyze the general equilibrium effects of such firm-level innovation on aggregate economic outcomes and find that trade induces growth and a convergence of the technology gaps between countries. Further, firm level innovation activity reduces in response to this convergence reflecting the lower opportunities to learn from foreign firms.In chapter 2, which is based on joint work with Stephen Ayerst, Faisal Ibrahim, and Gaelan MacKenzie, we study the role of knowledge embodied in traded goods for knowledge diffusion. We use US patent citation data to first, construct a knowledge input-output structure, and second, to measure embodied knowledge in products that is useful for the production of innovative ideas in a sector. We find that countries that import more knowledge from the United States that is useful for knowledge production in a specific sector also have increased innovation activity (R, researchers), innovation outputs (patents, citations), and finally employment and output production in that sector. Further, these results are stronger in richer economies, suggesting that they are better able to utilize frontier knowledge to generate new innovations. In chapter 3, which is based on joint work with Marijn Bolhuis and Diego Restuccia, we study how distorted rental markets for agricultural land lead to low agricultural productivity in India. We first recognize that there is large variation in land market institutions across different states in India due to colonial institutional precedence and differences in state-level land reforms implemented post-independence. We find that states with more rental market activity feature less misallocation, and also reallocate land more efficiently over time. Based on this observation, we build a model of land rental markets and heterogeneous farms and estimate land market frictions by state. Land market distortions contribute to about one quarter of the differences in agricultural productivity across states. Without rental activity agricultural productivity falls by 22%, and reallocating land more efficiently can increase agricultural productivity by 29% on average.