VictorJuiz/thesis huggingface dataset:
Hepatobiliary Pathology in Paediatric Inflammatory Bowel Disease

Background: Hepatobiliary pathologies, including primary sclerosing cholangitis (PSC) and drug-induced liver injury (DILI), are among the most clinically significant extraintestinal manifestations in inflammatory bowel disease (IBD), but paediatric data are scarce. We sought to 1) delineate the IBD phenotype of PSC-IBD in children; 2) investigate the disconnect between the increased colorectal cancer risk and mild clinical course described in PSC-IBD; and 3) examine the association between anti-TNFα exposure and liver injury. Methods: In Aim 1, a single-centre retrospective cohort study, children with PSC-IBD were each matched to two children with ulcerative colitis (UC) or IBD-unclassified (IBD-U). Longitudinal disease activity and anthropometrics were analyzed using mixed effects models, and time to event outcomes using Cox proportional hazards regression. In Aim 2, a single-centre cross-sectional study, correlations between symptoms, fecal calprotectin (FCP), endoscopy and histology were determined and compared between PSC-IBD and UC/IBD-U groups. Multivariable logistic regression and ROC analyses were used. In Aim 3, a large single-centre cohort of children receiving anti-TNFα for IBD was retrospectively reviewed, using multivariable Cox proportional hazards regression and RUCAM scores to assess causality. Results: In Aim 1 (74 PSC-IBD, 148 UC/IBD-U), paediatric PSC-IBD was associated with more pancolitis, rectal sparing and backwash ileitis, milder disease over time, including less frequent colectomy, and linear growth impairment. In Aim 2 (37 PSC-IBD, 50 UC/IBD-U), symptoms underestimated endoscopic and histologic activity in the PSC-IBD group, but FCP had excellent accuracy for mucosal healing. In Aim 3 (659 IBD patients), significant liver enzyme elevations occurred in 7.7% but, in the vast majority, alternate etiologies were identified, and biochemistry normalized spontaneously. There were only 9 patients in whom an alternate cause was not found, including one strongly suggestive case of DILI with autoimmune hepatitis (AIH) features that resolved with medication withdrawal. Conclusions: Paediatric PSC-IBD shares phenotypic features with adult PSC-IBD. We propose growth impairment as a novel, paediatric-specific element of the phenotype and subclinical inflammation as a possible mediator of the increased colorectal cancer risk. While liver enzyme elevations are fairly common in children with IBD receiving anti-TNFα, AIH-like DILI is rare, and most biochemical derangements resolve without medication cessation.

Keywords: Children
Colitis
Drug-induced liver injury
Inflammatory bowel disease
Liver
Primary sclerosing cholangitis
Advisor: Nguyen, Geoffrey C
The Role of Reading Fluency in Predicting Reading Proficiency Among French Immersion Elementary Students in Canada

This thesis comprises three studies that investigate the construct of fluency and its relationship with literacy outcomes among elementary students enrolled in Canadian French immersion programs. The first study examined multiple dimensions of fluency and its relationship to reading comprehension among grade 3 students. Fluency assessed across level (word fluency and text fluency) and language (English and French) converged onto a single factor of reading skill. This unitary construct of fluency uniquely predicted English and French reading comprehension beyond a number of language and literacy controls providing evidence for a cross-language relationship between fluency and reading comprehension among emerging English-French bilinguals. The second study investigated an emergent interaction between word reading fluency and vocabulary in predicting reading comprehension among students followed from the second to the third grade. In grade 2, word reading fluency and vocabulary contributed independently to reading comprehension, though an interaction between these variables was not observed in either language. By grade 3, an interaction between word reading fluency and vocabulary emerged and uniquely predicted reading comprehension in both English and French. Specifically, vocabulary was positively related to reading comprehension among students with moderate to high levels of fluency, while vocabulary did not contribute to reading comprehension among those who were less fluent. The third study investigated whether the addition of fluency-based measures (letter naming fluency, nonsense word fluency, and word reading fluency) to an existing screening battery would improve the ability to predict students at-risk for future word reading difficulties among kindergarten and first-grade students. Results demonstrated that the inclusion of fluency measures significantly improved upon a baseline battery of phonological processing tasks in the prediction of at-risk status based on English and French word reading measured one year later. Evidence for both within- and cross-language prediction of future reading risk was shown. Grade 1 screening resulted in more accurate prediction compared to screening in kindergarten, suggesting that predictive accuracy increases as children gain additional exposure to reading instruction. Taken together, these results add to the extant research highlighting the prominent role of reading fluency as well as its within- and cross-language relationship with literacy outcomes.

Keywords: bilingualism
French immersion
reading fluency
reading proficiency
vocabulary
Advisor: Chen, Xi
High-order Finite-volume CENO Scheme for Large-Eddy Simulation of Premixed Flames

A novel, parallel, high-order, central essentially non-oscillatory (CENO), cell-centered, finite-volume scheme is developed and applied to large-eddy simulation (LES) of turbulent premixed flames. The high-order CENO finite-volume scheme is applied to the solution of the Favre-filtered Navier-Stokes equations governing turbulent flows of a fully compressible reactive mixture on a three-dimensional, multi-block, body-fitted, computational mesh consisting of hexahedral volume elements. The CENO method uses a hybrid reconstruction approach based on a fixed central stencil. The discretization of the inviscid fluxes combines an unlimited high-order least-squares reconstruction technique based on the optimal central stencil with a monotonicity preserving, limited, linear, reconstruction algorithm. Switching in the hybrid procedure is determined by a smoothness indicator such that the unlimited high-order reconstruction is retained for smooth solution content that is fully resolved and reverts to the limited lower-order scheme, enforcing solution monotonicity, for regions with abrupt variations (i.e., discontinuities and under-resolved regions). The high-order viscous fluxes are computed to the same order of accuracy as the hyperbolic fluxes based on a high-order accurate cell interface gradient derived from the unlimited, cell-centered, reconstruction. The proposed cell-centered finite-volume scheme is formulated for three-dimensional multi-block mesh consisting of generic hexahedral cells and applied to LES of premixed flames. For the reactive flows of interest here, a flamelet-based subfilter-scale (SFS) model is used to describe the unresolved influences of interaction between the turbulence and combustion. This SFS combustion model is based on a presumed conditional moment (PCM) approach in conjunction with flame prolongation of intrinsic low-dimensional manifold (FPI) tabulated chemistry. Numerical results are discussed for a laboratory-scale lean premixed methane-air Bunsen-type flame. The performance of the proposed high-order scheme for turbulent reactive flows is analysed by a systematic mesh refinement study using different spatial orders of accuracy.

Keywords: Aerospace
Combustion
Computational Fluid Dynamics
High-Order Methods
Numerical Methods
Advisor: Groth, Clinton P.T.
Rhodium-catalyzed Arylation of Electron-deficient Alkenes for the Synthesis of Oxindoles and Gem-Difluoroalkenes

Transition-metal catalyzed carbon-carbon bond forming functionalization of alkenes is a powerful tool in organic chemistry, as it allows for rapid introduction of molecular complexity from simple starting materials. Most commonly used metal catalysts include palladium, nickel and rhodium, and they have been shown to enable the functionalization of alkenes. Compared to palladium and nickel, rhodium exhibits enhanced affinity towards alkenes and alkynes, which allows for highly chemo- and stereoselective transformations of these reactive functionalities. The rhodium-catalyzed 1,4-conjugate addition, also known as the Hayashi-Miyaura reaction, is one of the robust and mild olefin functionalization reactions. The rhodium enolate generated from the initial addition has been shown to further react with suitable electrophiles to construct multiple carbon-carbon bonds in a single operation. To further broaden the synthetic utility of these domino reactions, we investigated the reactivity of the rhodium enolate towards intramolecular cyclization reactions. The first chapter describes a rhodium-catalyzed transformation of o-bromoaniline derived acrylamides to a diverse array of 3-monosubstituted oxindoles. Our findings provided rapid access to a library of oxindole scaffolds from simple acrylamides and commercially available boronic acids. Inspired by our previous study, we examined the development of an analogous enantioselective transformation using o-bromoaniline derived 1,1-disubstituted acrylamides. The second chapter details the studies pertaining to the discovery of a chiral rhodium-phosphine complex to catalyze the enantioselective intramolecular reductive arylation reaction. Using our methodology, a diverse array of 3,3-disubstitued oxindoles was synthesized and the challenging construction enantiomerically enriched quaternary stereocenter was made possible. In the third chapter, our findings on the rhodium-catalyzed enantioselective defluorinative α-arylation of β-trifluoromethyl substituted secondary acrylamides are presented. We successfully demonstrated that this methodology can serve as an alternative approach in functionalizing the α-position of secondary amides, providing an efficient route to a novel class of gem-difluoroolefins containing a stereo-labile tertiary stereocenter.

Keywords: Arylation
Catalysis
Enantioselective transformation
Rhodium
Advisor: Lautens, Mark
Datacenter-optimized FPGAs

Large-scale deployment of field-programmable gate arrays (FPGAs) into datacenters has introduced new use cases that utilize the FPGA as a multi-user compute platform, require more on-chip memory, and can benefit even more from efficient hard blocks. Since FPGAs are not designed for this new use case, the burden of efficiently utilizing existing FPGAs for datacenter applications is on datacenter service providers and application designers. We propose to reduce this burden by optimizing the architecture of FPGAs to be more efficient for the emerging datacenter applications and create computer-aided design (CAD) tools that facilitate architecture modifications of FPGAs in general. In this thesis, we first create a CAD tool capable of automatic block RAM (BRAM) modelling and optimization for SRAM and MTJ memory technologies. We use this CAD tool to quantify the benefits of MTJ memory technology in BRAM design at both the block and system levels. In addition, we introduce COFFE 2, an automatic circuit modelling tool for heterogeneous FPGAs capable of accurately modelling arbitrary heterogeneous blocks using a proper mix of full custom and standard cell design flows. In addition, COFFE 2 can model complex fracturable logic tiles enhanced with hard arithmetic and can automatically floorplan them similarly to industrial practice. Next, we investigate virtualized FPGA designs that are more efficient at distributing data to one or more applications both in current FPGAs and in hard network-on-chip-enhanced FPGAs. Finally, we quantify the costs of keeping user data confidential against different threat levels in virtualized FPGAs, both in current FPGAs and in new architectures that we propose.

Keywords: Datacenter
Field-programmable Gate Array
FPGA Architecture
Advisor: Betz, Vaughn T
Micro- and Nano-scale Approaches for Disease Detection and Characterization

Devices that diagnose and characterize disease have the potential to greatly improve healthcare worldwide. This thesis explores a number of different elements pertaining to device design and application. A microfluidic device for the capture and profiling of circulating tumor cells (CTCs) is tested against a rabbit model of cancer. This device demonstrates both an increase in CTC load and aggressiveness which correlates with traditional computed tomography measurements. CTC biology is also shown to differ markedly from tumour precursor cells. Next, a study of gold microelectrode architecture is performed with the aim of improving performance towards biosensing. A unique regime of gold ion concentration, applied voltage, and electrolyte viscosity is determined which drives the assembly of a highly structured morphology. Further studies illustrate growth mechanisms and the sensitivity of the electrode towards biomolecule detection. Additionally, a microfluidic device for instrument-free manipulation of microscopic fluid quantities is developed. This design allows the metering and dispensing of reagents in an intuitive manner by combining a series of capillary valves and a simple push-button. This “Digit Chip” is applied to the detection of antibacterial susceptibility alongside a simple smart-phone based fluorimeter. Together these studies explore the application of electrochemical and microfluidic modalities to the realm of disease monitoring.

Keywords: device
diagnostic
electrochemistry
microfluidic
Advisor: Kelley, Shana O
A Molecular Structure Ontology for Medicinal Chemistry

The field of medicinal chemistry involves the design, synthesis, and development of new drugs that can be further enhanced with the application of ontologies. This thesis is divided into three parts: first, we discuss the need for a molecular structure ontology to aid us in the task of drug design and outline a requirements-driven approach that guided the design of the Molecular Structure Ontology (MoSt). Second, we demonstrate how the ontology is verified with incidence structures found in mathematical theories, and discuss the insights gained from the verification results. Finally, we demonstrate a new approach to building molecules by exploiting graph-theoretic properties of the ontology, outline characterization theorems that correspond to this model building process, and demonstrate how the ontology can help navigate the chemical search space for molecules.

Keywords: graph theory
knowledge representation
medicinal chemistry
molecular structure
ontologies
ontology engineering
Advisor: Grüninger, Michael
Life under Siege: Militarized Welfare in U.S.-occupied Okinawa

This dissertation examines the formations of what I have termed “militarized welfare,” that is, the multilayered ways in which discourses and practices of protecting and promoting life became intricately and intimately connected with militarism in Okinawa through the period of U.S. administration (1945-1972). This project draws on, and aims to contribute to, roughly three fields of scholarly literature: the politics of life and death, theorized most explicitly by Michel Foucault; U.S. (and Japanese) Cold War expansionism in the Asia-Pacific; and transpacific militarism. The central argument of my thesis is that the expansion of medical welfare in Okinawa was not antithetical to militarization, but in fact enabled it. I demonstrate this complementary relationship between warfare and welfare by closely examining the lived experiences of agents and subjects of welfare in/for occupied Okinawa – missionaries, medical practitioners, patients, Okinawan diaspora, and displaced farmers. While each actor engaged in promoting and protecting life in their own right, their acts of welfare were often easily appropriated by the U.S. military and U.S. and Japanese governments to serve their respective purposes. My thesis also tries to capture the moments when this affinity between welfare and the military was destabilized by actors who closely observed the limits of medical welfare in Okinawa. Chapter 1 explores the role of American Christianity in occupied Okinawa in producing the narratives of liberation and rehabilitation to transform Okinawa into a place worthy of salvation in the American imagination. Chapter 2 closely examines the lived experiences of public health nurses, illustrating how the education and mobilization of public health nurses constituted part of the biopolitical strategy of the U.S. Cold War empire. Chapter 3 explores the transpacific circuits of care and relief that connected occupied Okinawa, Hawaiʻi and beyond in multifaceted ways. I argue that transpacific biopolitical projects of “nurturing life” were facilitated through the necropolitical network that simultaneously shaped the Pacific in Cold War formations. Chapter 4 focuses on the protest by displaced farmers and shows how land and life itself became an effective basis for the struggle against militarism. However, these movements were soon depoliticized through social security measures.

Keywords: Biopolitics
Cold War
Japanese colonialism
Militarism
Okinawa
U.S. military occupation
Advisor: Yoneyama, Lisa
Impacts of Late Quaternary Climate Changes on the Southern African Savanna Biome

Understanding the role of climate in driving vegetation change over recent geological time provides critical information for predicting future changes. Pollen analysis can be used to track past vegetation change, and to reconstruct Late Quaternary paleoenvironments. Pollen assemblages can assist in understanding biome responses to climate change if there is reasonable probability that they represent specific biomes. To test if biomes can be statistically described in terms of pollen assemblages, supervised machine learning methods are used to classify modern African biomes using modern pollen data. The Random Forest classifier is identified as the best method for classifying biomes using high dimensional pollen data with the ability to predict African biomes (arid, montane, tropical and subtropical closed and open systems, e.g. forests and savanna/grassland) to a high degree of accuracy and precision. The Random Forest classification model is then regionally developed for Southern Africa to investigate past savanna-grassland dynamics. An expanded modern pollen dataset for Southern Africa was compiled, and linked with contemporary biomes to build regional classification models. After validation, the models are applied to a fossil pollen record for probabilistic reconstructions of past biomes. The results show that savanna likely dominated this region for most part of the past 60,000 years. However, the glacial-interglacial transition (10,000-11,900 years ago) shows increased likelihood of grassland and rapid shifts in biome positions, offering a more complex and nuanced view of past savanna vegetation dynamics. Lastly, a late Holocene record is examined to understand more iirecent changes in savanna biome in semi-arid Southern Africa. A gradual development of relatively wetter local conditions beginning with the Northgrippian-Meghalayan transition (ca. 4.5-4 ka) is evidenced by multiple proxy records obtained from a paleomarsh context. The wet phase lasts ca. 2000 years and is characterized by increased organic matter content, dominance of taxa indicative of marshy conditions, presence of freshwater fungi, and isotopic composition of soil organic matter consistent with the presence of woody vegetation. This record provides evidence for wet conditions starting around 4.2 ka cal BP that is consistent with other regional and global records.

Keywords: data analysis
machine learning
pollen
Quaternary
savanna-grassland dynamics
Southern Africa
Advisor: Finkelstein, Sarah A
Reducing Implicit and Explicit Racial Biases among Young Children

Racial biases exist in our society. These biases, when left unchecked, exert far-reaching adverse impacts at personal and societal levels in education, health care, employment, and justice. The preschool period is formative in the development of racial bias. Until the present thesis, it was unknown whether children at preschool-age would display racial biases against other-race people, and if yes, how to reduce them. In Chapter 2, I developed a child-friendly implicit racial bias test and found the early emergence of implicit and explicit racial biases among children as young as 3-years old. The same pattern was consistently found in three distinct cultures: China, Cameroon, and Canada. I also found that the level of racial bias was affected by perceived social status between own- vs. other-race and their level of contact with other-race members. It was the first set of studies that examine the phenomenon of racial bias in preschool-age children from various cultures. In Chapter 3, I developed a novel training method, referred to as individuation training, in which children practiced the process of treating other-race members as unique individuals rather than members of social groups. I provided the evidence that individuation training reduced implicit racial biases among children in China (Experiment 1) and Canada (Experiment 2), and that the training effects were sensitive to children’s exposure to racial diversity. In Chapter 4, I further examined the long-term effects of the novel individuation training method. I found that repeated individuation training reduced Chinese children’s implicit racial bias for the long term (60 days). Together, my thesis suggests that racial bias emerges early in preschool-age and training children to treat other-race members as unique individuals reduce implicit racial bias in both short and long terms.

Advisor: Lee, Kang