VictorJuiz/thesis huggingface dataset:
Functional Analysis of Risk Single Nucleotide Polymorphism and Long Noncoding RNA in Prostate Cancer
Keywords: Bifunctional promoter-enhancer
Cancer
Epigenetics
Long noncoding RNA
Prostate Cancer
Single nucleotide polymorphism

Prostate cancer is the most commonly diagnosed non-cutaneous cancer in men worldwide. While most low-risk prostate cancer patients have a favourable clinical outcome, intermediate- and high-risk patients with aggressive forms of the disease often relapse despite the initially effective local and conventional androgen-deprivation therapies. Therefore, two main challenges in the field of prostate cancer are patient stratification into appropriate risk groups through prognostic biomarkers and novel therapeutic options for patients with aggressive prostate cancer. Prostate cancer has a strong genetic component, with Genome-wide Association Studies (GWAS) identifying over 150 risk single nucleotide polymorphisms (SNPs). While these risk SNPs are associated with prostate cancer predisposition and a few also associated with disease progression, their functional mechanisms remain elusive. Here, I evaluated the association of the risk SNP rs11672691 with prostate cancer progression and its clinical relevance, and uncovered its regulatory mechanisms at a novel bifunctional enhancer-promoter element to dysregulate two gene isoforms of a long noncoding RNA (lncRNA) PCAT19. Furthermore, I validated the oncogenic properties of the lncRNA PCAT19, and revealed its function in prostate cancer progression through the upregulation of a subset of cell cycle genes with the RNA binding protein HNRNPAB. My work signifies the clinical importance in understanding the functional mechanisms of prostate cancer risk SNPs and lncRNAs in prostate cancer. Additionally, my work also shed light on the function and molecular mechanisms of a novel class of regulatory elements in the human genome, and its role in cancer aggressiveness.
Economies of Things: Material Attachments in British Romantic Literature
Keywords: Austen
Jane
Burke
Edmund
Economics
Material things
Romantic literature
Wordsworth
William

Romantic literature reveals a persistent attention to everyday material things, such as a sheepfold, a house, and a spinning wheel. Romantic texts indicate that Britons used these things as anchors to build their identities, memories, and relationships. Yet, while recognizing the importance of mnemonic and emotional ties between people and things, these texts nonetheless portray these bonds as increasingly unstable. In late eighteenth- and early nineteenth-century Britain, changes in two areas of the economy—paper money and the rise of consumerism—transformed the ways in which Britons understood their relationships to things, fostering more indirect, fleeting interactions with the material world, creating a gap between people and things. While some writers depict this new distance from things as tragic, Economies of Things does not portray this gap solely as a loss. As authors mobilize aesthetics to address the problem of detachment from things, their responses inspire some of the central aesthetic concerns of Romanticism. Tracing these literary responses to economic change—taking as primary case studies the writings of Austen, Burke, Wordsworth, and De Quincey—I uncover strong connections between aesthetics and economics in Romantic-era literature. While aesthetic inventions become solutions for an economic problem, economics becomes a discussion ground for aesthetics. Late eighteenth- and early nineteenth-century conversations about economy take on a peculiarly “Romantic” character by taking up concerns such as imagination, creativity, and aesthetics. The gap between people and things inspires two theories of the imagination: Wordsworth’s portable creativity, adapted to the transience of consumerism, and De Quincey’s grotesque, consumer imagination, founded on the destruction rather than the production of material things. This gap also shapes theories of the sublime and the grotesque. To prevent the powerful infinity of paper money from being interpreted as sublime, Burke theorizes an alternative infinity: the infinite grotesque. Based in bodily processes that dissolve formed, solid material things into endless streams of organic matter, this aesthetic category reappears in the works of De Quincey, Wordsworth, and the caricaturists Gillray and Newton. From the stories of lost bonds between people and things emerge aesthetic theories that shape the movement we call Romanticism.
Fixing History: Time, Space, and Monastic Identity At Saint-Aubin in Angers ca. 1100
Keywords: monastic art
romanesque art
Saint-Aubin

This dissertation examines textual and visual production at the abbey of Saint-Aubin in Angers ca. 1100. Composed of three sumptuously illuminated manuscripts, a cartulary, and wall paintings and building projects in the abbey and throughout its network of dependencies, the extensive material investment at Saint-Aubin is indicative of institutional self-definition at the end of the eleventh century. Fragmentation of scholarship among specializations and media has isolated material culture from events, documents, and human agents, restricting academic discourse and implying a separation of art from social history. Taking a synthetic approach to material culture, this dissertation integrates different modes of institutional discourse to probe the role of the making and experience of art objects in the construction of monastic identity. The first half of this dissertation explores the concurrent territorial expansion, documentary drive, political alienation, and material investment as strategies in a multimedia and multidiscursive institutional affirmation at late-eleventh-century Saint-Aubin. In response to interventions from the papacy and the counts of Anjou, Saint-Aubin increasingly strove to articulate its institutional autonomy as pertaining to internal elections, landholding, and liturgical rights. Guided by a historiographical impulse, the monastic scribes and illuminators of the cartulary, the vita of St. Albinus, and the Second Bible materially constructed their aspirational institutional present as an ontological reproduction of a sacred monastic past; a past wherein total institutional autonomy was a foundational imperative. The second part of this dissertation addresses the role of the material culture of Saint-Aubin in the internalization and reification of monastic identity by its targeted audience. An interrogation of extensive visual symbiosis between manuscript illumination, monumental sculpture, and mural paintings reveals a cognitive spatial category in which various ontological, narrative, and historical spaces were associated with, and reproduced within, the church of Saint-Aubin and the body of St. Albinus. Through experience of manuscript illumination, architecture and fresco, rite, sermon, and cartulary transcription within this spatial category, institutional historiography of representation could become transformed into lived and embodied identity by the monks. Examined interdisciplinarily, Saint-Aubin provides an opportunity to establish a more holistic approach to the role of material culture in the creation of identity.
Hepatobiliary Pathology in Paediatric Inflammatory Bowel Disease
Keywords: Children
Colitis
Drug-induced liver injury
Inflammatory bowel disease
Liver
Primary sclerosing cholangitis

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.
The Role of Reading Fluency in Predicting Reading Proficiency Among French Immersion Elementary Students in Canada
Keywords: bilingualism
French immersion
reading fluency
reading proficiency
vocabulary

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.
High-order Finite-volume CENO Scheme for Large-Eddy Simulation of Premixed Flames
Keywords: Aerospace
Combustion
Computational Fluid Dynamics
High-Order Methods
Numerical Methods

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.
Rhodium-catalyzed Arylation of Electron-deficient Alkenes for the Synthesis of Oxindoles and Gem-Difluoroalkenes
Keywords: Arylation
Catalysis
Enantioselective transformation
Rhodium

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.
Datacenter-optimized FPGAs
Keywords: Datacenter
Field-programmable Gate Array
FPGA Architecture

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.
Micro- and Nano-scale Approaches for Disease Detection and Characterization
Keywords: device
diagnostic
electrochemistry
microfluidic

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.
A Molecular Structure Ontology for Medicinal Chemistry
Keywords: graph theory
knowledge representation
medicinal chemistry
molecular structure
ontologies
ontology engineering

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.