VictorJuiz/thesis huggingface dataset:
New Methods for the Site-selective O-H and C-H Functionalization of Sugars

Carbohydrates are among the most abundant biomolecules in nature and serve as the metabolic precursors to nearly all other biomolecules. The immense structural diversity found among carbohydrates has resulted in an equally diverse profile of biological functions, including roles in energy storage, structural support, and cell-cell communication. Recognizing the myriad of vital roles carbohydrates serve in animals, development of carbohydrate-based drugs has been pursued intensely and has resulted in the prolific use of drugs like empagliflozin, enoxaparin and molnupiravir. The function of most natural carbohydrates is unknown and glycobiological research on them is limited by their availability. To facilitate this research, new synthetic methods able to generate the sophisticated functionalization patterns found in these molecules must be developed. Direct methods for the site-selective installation of functional groups onto carbohydrates are desired as they avoid the process inefficiencies caused by use of protecting groups. In this thesis, new catalytic methods for the site-selective O-H functionalization of carbohydrates will be covered. Chapter 1 will cover the borinic-acid catalyzed sulfation of carbohydrates and Chapter 2 will cover the boronic-acid catalyzed sulfamoylation of carbohydrates. Photoredox catalysis has resulted in the revitalization of radical chemistry by enabling access to open-shell intermediates under mild conditions. In conjunction with hydrogen atom transfer catalysis, activation of C-H bonds in complex molecules is possible. Given the prominence of hydrogen atom transfer processes in carbohydrate biosynthesis, photoredox-mediated hydrogen atom transfer catalysis can be used as a tool to activate the C-H bonds within sugars. Novel site-selective methods for the C-H functionalization of sugars will also be covered in this thesis as well. Chapter 3 will cover C-H alkylations and Chapter 4 will cover redox isomerizations. Finally, Chapter 5 will cover the site-selective oxidations of carbohydrates, a longstanding goal of our research program.

Keywords: Carbohydrate
Isomerization
Oxidation
Photoredox
Sulfamoylation
Sulfation
Advisor: Taylor, Mark S
Contextualized Rehabilitation Technologies: An Exploration into Anger Dyscontrol after Traumatic Brain Injury

Emergent pervasive computing technologies offer new opportunities to extend the rehabilitation paradigm beyond the hospital setting and into the context of everyday life – an opportunity area we frame as contextualized rehabilitation technologies. The development of such technologies is an interplay of clinical expertise, human-centered design, and technology readiness. Navigating this landscape, however, is fraught with challenges as one needs to balance rehabilitation opportunities against the practicalities of technology design. Pushed too far to one side, and one can either far-exceed the capabilities of emerging technologies, or miss an opportunity to capitalize on technology readiness. This thesis seeks to explore the design space of contextualized rehabilitation technologies, particularly with the focus on outpatient cognitive rehabilitation for individuals with traumatic brain injury (TBI). In Part 1 of the thesis, we broadly explore the design space between outpatient cognitive rehabilitation and pervasive computing, by developing a new co-design process that enables wide ideation of possible design ideas and considerations. In Part 2 of the thesis, we conceptualize an outcome idea from Part 1 as an exploratory case-study of a contextualized rehabilitation technology. Specifically, we examine the potential of photoplethysmography (PPG), a physiological wristband sensor, to be used to estimate emotion for the self-management of anger after TBI.

Keywords: Affective Computing
Co-design
Emotion
Pervasive Computing
Rehabilitation
Traumatic Brain Injury
Advisor: Mihailidis, Alex
Green, Robin EA
MV Polytopes and Reduced Double Bruhat Cells

When G is a complex reductive algebraic group, MV polytopes are in bijection with the non-negative tropical points of the unipotent group of G. By fixing w from the Weyl group, we can define MV polytopes whose highest vertex is labelled by w. We show that these polytopes are in bijection with the non-negative tropical points of the reduced double Bruhat cell labelled by $w^{-1}$. To do this, we define a collection of generalized minor functions $\Delta_\gamma^\text{new}$ which tropicalize on the reduced Bruhat cell to the BZ data of an MV polytope of highest vertex w. We also describe the combinatorial structure of MV polytopes of highest vertex w. We explicitly describe the map from the Weyl group to the subset of elements bounded by w in the Bruhat order which sends $u \mapsto v$ if the vertex labelled by u coincides with the vertex labelled by v for every MV polytope of highest vertex w. As a consequence of this map, we prove that these polytopes have vertices labelled by Weyl group elements less than w in the Bruhat order. A motivation for studying MV polytopes of highest vertex w is that they are the finite-type equivalent of lower affine MV polytopes for $\widehat{SL_2}$. We show that for $\ell(w) \leq 3$, lower affine MV polytopes with highest vertex w are in bijection with the non-negative tropical points of the reduced double Bruhat cell labelled by $w^{-1}$ for $\widehat{SL_2}$. Finally, MV polytopes in the finite case are defined by the tropical Plucker relations while rank 2 affine MV polytopes are defined by ``diagonal relations''. We prove that for $B_2$ polytopes, these diagonal relations hold and are equivalent to the tropical Plucker relations.

Advisor: Kamnitzer, Joel
The Impacts of Rohingya Refugee Humanitarian Aid Policies on Local Bangladeshi Communities

Long-term refugee camps are a significant outcome of the record 82.4 million displaced people globally, with 85 percent of refugees in camps in the Global South. Refugee camps in the Global South are growing ever larger as countries in the Global North close their borders to refugees. Refugee camps are well studied in the field of forced migration, but most research focuses on the lives of refugees. What is missing in this field is research on the social-environmental impacts of long-term refugee aid policies on non-refugee populations living in and around the camps: local people who are affected by refugee aid policies but are virtually invisible to aid agencies. There is a gap in the examination of the hardening of borders between camp and local communities, between the categories of refugee and citizen, between who is eligible for aid, and how this denies the deep entanglements of social, economic, and ecological life across these borders while deepening the most adverse impacts. Much of the blame for these impacts fall on the shoulders of refugees themselves, fueling anti-refugee xenophobia. This production of vulnerability through aid policies and practices is understudied and impacts of aid policies on local communities garner little attention from aid agencies or donor states. I argue that aid policies intended for refugees (re)produce gendered vulnerability of local, non-refugee “host” communities living in and around refugee camps and in this way, increases anti-refugee xenophobia. I explore the Rohingya refugee “mega camp” in Bangladesh and how aid policies shaping this camp affect local social and environmental dynamics. This dissertation explores three scenarios where aid policies affect Bangladeshi households. The first chapter explores how the lives of forest-dwelling Bangladeshi families forcibly surrounded by the camp have changed; the second chapter looks at how aid policies (re)produce gendered vulnerability to climactic events; and the third chapter examines how fractured jurisdiction between aid agencies and the Bangladeshi government affects aid practices and fuels anti-Rohingya xenophobia. Investigating the impacts of refugee aid on non-refugees is one way to diversify forced migration and vulnerability research, adding new insight to the production of anti-refugee xenophobia.

Keywords: Bangladesh
Gender
Humanitarian Aid
Migration
Refugee Studies
Rohingya
Advisor: Cowen, Deborah
Young Children’s Perspectives on their Well-being at School

Understanding young children’s perspectives on their well-being at school is essential to creating environments that best support their development. Well-being is a balance of positive affect, negative affect, and an overall evaluation of life (Diener, 1984). My study seeks to better understand young children’s perspectives on their well-being at school. Participants were 4- to 6-year-old children and their educators from two public schools and one independent school in Ontario. First, I determined whether children’s perspectives of their well-being at school align with those of educators. Children and educators completed a questionnaire – the Multidimensional Life Satisfaction Scale adapted, (MLSS-adapted; Huebner & Gilman, 2002). My analysis of children’s and educators’ perspectives on the questionnaire showed that children’s and educators’ perspectives on children’s well-being at school are different. Then, I further examined children’s perspectives through an open-ended story completion task where children were told the beginning of a story about a character that either has a good dream or a bad dream about school. Children were asked to complete the story by telling about all the good things or bad things that happened to the character. Themes from children’s good dream stories included mentions of food, friends, “other social reference” (e.g., children in general), play, and positive feelings. Children’s bad dream stories included mentions of physical or emotional harm, negative feelings, and “other social reference”. Finally, I studied the relationship between children’s story themes and their well-being at school as indicated by their responses on the questionnaire. Play and friends were frequently mentioned by children with higher well-being in good dream stories and a failure to have expectations met were mentioned frequently by children with lower well-being in bad dream stories. My study showed young children have insights into their experiences at school that are different than those of their educators. By using measures that consider children’s developmental abilities, young children can meaningfully participate in research. Children’s unique perspectives can be used to shape schools and curriculum that best support children’s well-being.

Advisor: Volpe, Richard
Comay, Julie
Segregation, Capture and Recovery of Circulating Clonal Plasma Cells in Peripheral Blood of MM patients using Micropillar-integrated Microfluidic Device and its Cinical Applicability

Multiple myeloma (MM), the disorder of plasma cells, is the second most commonly seen hematological cancer. The current gold standard for MM diagnosis includes invasive bone marrow aspiration. However, it lacks the sensitivity to detect minimal residual disease, and the nonuniform distribution of clonal plasma cells within bone marrow often results in inaccurate reporting. Serum and urine assessment of monoclonal proteins is another commonly used approach for MM diagnosis. Although non-invasive, the level of paraprotein elevation is too low for detecting minimal residual disease and non-secretive MM. Circulating CPCs (cCPCs) have been reported to be present in the peripheral blood of MM patients and is emerged as an important biomarker in evaluating the Minimal Residual Disease status in MM. The elevation of cCPCs in patients is closely related to the recurrence of the disease. Compared to the conventional bone marrow aspirate, it can be accessed regularly in a non-invasive manner. Over the past decade, microfluidic techniques have been widely explored as a platform to segregate the rare cells in blood with the advantages of easy manipulation and relatively low cost. In this thesis, we present a novel mechanical property-based microfluidic platform to segregate cCPCs and successfully demonstrate its clinical applicability in MM. First, we developed a microfluidic device based on the unique physical and mechanical properties of MM cells. The prototype was testified by spiking human myeloma cell lines in healthy donor blood, and the key parameters such as enrichment ratio and capture efficiency were also evaluated. Next, we used our developed microfluidic platform to explore its clinical utility in comparison with existing methods of Multiparameter Flow Cytometry and Serum Protein Electrophoresis analysis. MM blood samples of different disease stages were processed through the microfluidic device. In addition, we conducted longitudinal studies on patients, monitoring the disease status before and after treatment. We recorded cCPCs level detected by microfluidic chip and compared it in parallel with the paraprotein level detected by serum protein electrophoresis. Furthermore, the ability to retrieve the cCPCs from microfluidic chip was also demonstrated and the subsequent cytogenetic analysis was performed. The MM-related genetic mutations were identified.

Advisor: Lidan, You LY
German Economists and the Intersection of Science and Politics: A History of the Verein für Sozialpolitik, 1872-1972

This dissertation examines the intersection of politics and scholarly activism in Germany through the prism of one organization, the Verein für Sozialpolitik. The history of the Verein highlights the deep connections between the state, science, and politics from the founding of the Kaiserreich to the establishment of the Bundesrepublik. Created in a moment of intense debate over the social question, particularly within German liberalism, the Verein pursued two aims at the same time: to educate middle-class opinion on the plight of workers in an age of rapid industrialization, and to influence government policy through detailed investigations of socio-economic phenomena. The Verein’s key contribution in its early years was propelling the notion of Sozialpolitik onto the national stage. However, the Verein increasingly evolved into a society of professional economists, although the tensions between science and politics remained. The Verein served as a space where the major issues related to Germany’s social, political, and economic development took place among middle-class elites, particularly academics. Throughout its existence, the Verein played a crucial role in defining the boundaries between liberalism, conservatism, and socialism in German intellectual life. But its early emphasis on the social question gradually grave way to increasing focus on economic problems, particularly as Sozialpolitik came to be viewed as a politically divisive force. The history of the Verein expresses the evolving nature of economic liberalism in German economic thought, particularly by showcasing the transformation of liberal conservatism from the Kaiserreich to the West German Bundesrepublik. Based on research in archives in Germany, Switzerland, Austria, and the United Kingdom, this dissertation traces the origins of the liberal democratic consensus among German economists that became firmly established after 1945. It details the fate of the Verein’s left wing and explains why left-leaning economics failed to take hold in the economic mainstream in Germany. By taking a longer view of the history of social and economic thought in Germany and by also focusing on the most important and consequential association for economists in German-speaking Europe, it highlights the continuities and discontinuities that defined German liberalism between 1872 and 1972.

Keywords: Economic Institutions
Kathedersozialismus
Liberalism
Neoliberalism
Political Economy
Verein für Sozialpolitik
Advisor: Jenkins, Jennifer L
A flexible summary statistics-based colocalization method to integrate omics data

Colocalization methods that integrate omics data can help define the mechanism by which Genome-wide association study (GWAS) loci contribute to disease. Contemporary colocalization analytical tools must be valid and powerful under several complex scenarios such as for summary statistics calculated from meta-analyses or using related or overlapping samples; in the presence of a composite null hypothesis; and in regions with high linkage equilibrium (correlation between genetic markers) and/or allelic heterogeneity. In this thesis, we develop colocalization methods and tools to address these complex scenarios through a frequentist and summary statistics-based approach. The proposed methods could assess colocalization, for example, between a primary phenotype and gene expression, or between other omic-data including DNA methylation (meQTLs), protein QTLs (pQTLs) or metabolites (metQTLs). Chapter 1 provides the scientific motivation and genetic background for calculating the summary statistics. Chapter 2 focuses on the development of the Simple Sum (SS) colocalization framework, which is powerful in regions with high linkage disequilibrium and allelic heterogeneity. However, the SS is restricted to implementation in regions with sufficient eQTL evidence to achieve type I error rate control. This inspired the work of Chapter 3 where we develop a more flexible procedure based on the SS (SS2), which avoids a priori eQTL assumptions. We advance the utility of the method to complex scenarios, such as correcting for multiple hypothesis testing in the presence of a composite null hypothesis, analyzing meta-analysis summary statistics with and without related individuals, and adjusting for overlapping samples between studies. Chapter 4 describes the implementation of the SS2 methodology in a web-based tool, LocusFocus, with extended R functions. Currently LocusFocus is used by over 100 new users per month according to Google Analytics. Chapter 5 concludes with a discussion of the impact and limitations of the work in this thesis, and describes some concrete steps that have been taken towards future work.

Keywords: colocalization
composite null hypothesis
cystic fibrosis
lung disease
meta-analysis
Simple Sum 2
Advisor: Strug, Lisa L
Sun, Lei L
How to Be a Pragmatist in the End: Objectivity, Skepticism, and the Demands of Agency

Pragmatists face serious difficulties in accounting for the objectivity of truth and knowledge. For they clarify our beliefs’ meaning and truth by appeal to their practical success, and practical success seems relative to particular contexts, or even particular believers. Some pragmatists verge on simply accepting this consequence, but others attempt to secure objective standards of truth and justification. My dissertation interprets and evaluates this objective pragmatist tradition. I argue for three key claims. First, there are two conceptions of objectivity prominent within this tradition, which stand in serious mutual tension: an empiricist conception, on which objective constraints on belief are provided by possible experiences, and a realist-causal conception, on which they are provided by causal interaction with the mind-independent natural world. These conceptions dominate in different historical periods, marking the transition from classical pragmatism to neo-pragmatism. The classical pragmatists most concerned with objectivity, C. S. Peirce & C. I. Lewis, opt for the former conception (notwithstanding apparent realist-causal sympathies in Peirce’s work that ultimately explain the emergence of the latter). Neo-pragmatists who preserve objectivity, like Wilfrid Sellars, opt for the latter. Second, neither camp effectively deploys its conception to provide an adequate account of the epistemic objectivity of our beliefs and assertions: the former camp falls prey to phenomenalism (and so, among other problems, fails to accommodate other minds satisfactorily), while the latter fails in its effort to leverage semantic externalism into an adequate response to skepticism. Finally and in consequence, pragmatism's most fruitful contribution to thinking about objectivity turns out not to lie in its treatments of meaning and truth, but in its independent epistemology: specifically, in Peirce’s and Sellars’s arguments that our right to accept our basic empirical beliefs is a pragmatic warrant. I develop this stance by arguing that our warrant to accept that our perceptual beliefs are likely to be true derives from our commitment to being effective agents and, ultimately, from the value of control over our empirical circumstances.

Keywords: American Philosophy
C. I. Lewis
Charles Sanders Peirce
History of Analytic Philosophy
Pragmatism
Wilfrid Sellars
Advisor: Misak, Cheryl
Development of an Anatomical Proteomic Atlas of Glioblastoma

Glioblastoma (GBM) is the most common brain tumour amongst adults with a dismal median survival of 15 months, despite multimodal therapy, including maximal resection and chemotherapy. Classically, GBM has been defined by hallmark histomorphological features, including cellular (CT) and infiltrating tumour (IT) areas, regions of microvascular proliferation (MVP), and hypoxia where the tumour cells palisade around necrosis (PAN). These diverse histomorphologic niches, create a heterogeneous tumour microenvironment (TME) that contributes to tumour evolution and treatment resistance. To better understand the molecular tenants of these histomorphological features, I created an anatomical proteomic atlas of human glioblastoma by excising these regions, using laser capture microdissection techniques, and performing liquid-chromatography based proteomics. This unique resource highlighted that GBM intra-tumour heterogeneity can be defined across a› three-dimensional axis including MYC-, KRAS- and hypoxia programs. Furthermore, utilizing these reference proteomic profiles, I leveraged machine learning to deconvolute and estimate niche proportions in independent bulk based proteogenomic efforts. This approach revealed a strong association of the proneural subtype with a diffusely infiltrating phenotype providing new insights for the genetic drivers and poor response of this subtype. Finally, I compiled these proteomic profiles to develop a publicly available bioinformatics portal for knowledge dissemination in hopes of accelerating our understanding of glioblastoma biology. Together these works highlight the importance of accounting for regional proteomic profiles in GBM to nominate phenotypic programs and unify biological theories. Generalization of the approaches and data outlined in this thesis can help explore other intra-tumoural aspects of tumour heterogeneity including divergent spatially distributed tumour subpopulations and structures.

Advisor: Diamandis, Phedias