VictorJuiz/thesis huggingface dataset:
An Image-Guided Computational Framework for Intraoperative Fluorescence Quantification

Fluorescence-guided surgery uses molecular agents that target tumors, lymph nodes, or blood vessels. Optical devices measure fluorescence light emissions from these functional biomarkers to help surgeons differentiate diseased and healthy anatomy. Clinical indications for fluorescence guidance continue to expand, and are being spurred by the rapid development of new agents that improve biological targeting. To capitalize fully on these advances, there is a corresponding need to engineer high-resolution imaging systems that provide objective measurements of fluorescence. The key innovation in this thesis is the development of a computational framework for image-guided fluorescence quantification. The underlying principle is to directly incorporate spatial localization of patient anatomy and optical devices into multi-stage models of fluorescence light transport. This technique leverages technology for intraoperative cone-beam CT (CBCT) imaging and surgical navigation to account for tissue deformation and surgical excision. A novel calibration algorithm enables real-time compensation for fluorescence variations due to illumination inhomogeneities, tissue topography, and camera response. In endoscopic images of realistic oral cavity phantoms, navigated light transport modeling not only improved fluorescence quantification accuracy at the tissue surface, but also reduced tissue misclassification in a simulated model of surgical decision making (e.g., tumor vs. normal, perfused vs. necrotic) in comparison to an unguided approach. The image-guidance framework was also applied to a finite-element implementation of diffuse fluorescence tomography. Camera and laser tracking enabled adaptive, non-contact acquisition. Sub-surface spatial priors from CBCT imaging improved the depth-resolved spatial resolution and fluorescence quantification accuracy in liquid phantom experiments. These investigations elucidate the deleterious effects of view-dependent illumination inhomogeneities and depth-dependent diffuse tissue transport on fluorescence quantification accuracy. Moreover, the direct use of 3D data from a CBCT-guided surgical navigation system in computational light transport models improves fluorescence quantification and tissue classification accuracy in pre-clinical experiments. Future clinical translation of these fluorescence-guided surgery techniques is an essential next step to further assess the potential impact on intraoperative decision making and cancer patient care.

Keywords: Biophotonics
Cancer Surgery
Computational Light Transport
Fluorescence Quantification
Image-Guided Surgery
Intraoperative Imaging
Advisor: Jaffray, David A
Citation, Collaboration, and Appropriation in the Works of Andrew and Nora Lang

This dissertation argues that the representations and practices of authorship in the works of Andrew Lang (1844-1912) and Nora Lang (1851-1933) emblematize this literary couple’s struggles to define the nature of literary creativity and, by extension, to determine whose creative efforts are worthy of acknowledgment. Chapter One reveals the importance of adaptation to Andrew’s definition of creativity by considering the relationship between his first book, Ballads and Lyrics of Old France: With Other Poems (1872), and three texts that shaped his conception of authorship: Walter Scott’s Minstrelsy of the Scottish Border (1802-03), E.B. Tylor’s Primitive Culture (1871), and Walter Pater’s Studies in the History of the Renaissance (1873). Chapter Two focuses on the three-year period (1887-90) during which Andrew, now a well-established man of letters, deployed his own authority to defend his friend H. Rider Haggard against charges of plagiarism. I focus on three of his creative works that claim adaptation is a necessary precondition of origi-nality: He (1887), a parody of Haggard’s She (1887); “From Mr. Allan Quatermain to Sir Henry Curtis” (1890), an epistolary yarn wherein Haggard’s hero rescues the Stranger from Olive Schreiner’s The Story of An African Farm (1883); and The World’s Desire (1890), Lang and Haggard’s co-authored sequel to the Odyssey. In Chapter Three, I illustrate the ways in which this same insistence on the communalization of literary materials, and folk- literature in particular, paradoxically obscures Nora’s responsibility for the popular Fairy Book series (1889-1913). Nora’s work is, I demonstrate, consistently represented as domestic labour rather than authorship by Andrew’s prefaces, advertisements for the series, and contemporary reviews. Chapter Four examines her resistance to this misrepresentation. I focus on The Strange Story Book (1913), arguing that the volume’s seemingly eclectic contents — a short biography of the recently-deceased Andrew, appropriated Tlingit legends, and stories of gender- nonconforming and adventurous women — indicate both Nora’s participation in and challenging of the model of author-ship promoted by her husband. Both Langs’ works, I conclude, have much to tell us about the literary, political, and ethical valences of citation.

Keywords: Andrew Lang
Authorship
Children's literature
Citation
Nora Lang
Victorian literature
Advisor: Bolus-Reichert, Christine
A Theory About Indigenous Taxation Powers

This paper proposes that taxation powers are culturally specific constructs by analyzing the content and underlying values, social organization, customs and institutions determining how Indigenous peoples of the Pacific Northwest Coast (Northwest Coast communities) understand taxation and exercise their taxation powers. The first chapter examines the non-monetary socio-economic organization of Northwest Coast communities to determine whether or not these communities practice taxation and exercise taxation powers. The second chapter analyzes, from a tax law perspective, the socio-economic characteristics of Northwest Coast communities to identify the criteria of legitimacy, limits and principles that inform how these communities understand taxation and exercise taxation powers. The final chapter explains why the emergence of market economies and monetary exchanges has not changed how Northwest Coast communities understand taxation and exercise taxation powers and explains how Northwest Coast taxation systems function according to kinship values, organization, customs and institutions.

Keywords: Indigenous Peoples
Northwest Coast
Taxation
Taxation Powers
Advisor: Sanderson, Douglas
A Tale of Two Metaphors: A Narrative Take on the Canadian Constitution

This essay sheds light on the fundamental role that metaphors and narratives play in shaping how we talk, think, and argue, about the Constitution. Specifically, it makes the case that Canadian constitutional law is fashioned, to a large extent, by two competing types of metaphors: dynamic and static. Each of these categories, the essay seeks to show, stands for a different conception of the Constitution and, as such, influences the types of stories we tell about it. Each sustain, as the two case studies illustrate, dominant narratives about the Constitution, narratives whose structure essentially corresponds to the archetypal birth and rescue stories. The idea behind this essay is that, insofar as narratives and metaphors influence our cognition and help us reason about ideas and concepts ―a great part of our work as jurists― we would be wise to pay attention to them. Cet essai souligne le rôle fondamental que jouent narratifs et métaphores en façonnant la manière que notre Constitution est conceptualisée, discutée, et débattue. Plus précisément, l’essai soutient que deux importantes catégories de métaphores, statiques et dynamiques, sont au cœur du droit constitutionnel canadien. Chacune de ces catégories représente une vision différente de la Constitution et, en tant que telle, elle influence le type d'histoires que nous en racontons. Chacune soutient un narratif particulier, un narratif qui renvoie, en règle générale, soit à la « naissance » ou au « sauvetage » de notre texte fondateur. L'idée derrière cet essai est que, dans la mesure où les narratifs et les métaphores influent sur notre cognition et nous aident à raisonner dans l’abstrait, une grande partie du travail juridique, nous serions avisés de leur prêter une plus grande attention. C'est, en somme, un appel à une prise de conscience narrative.

Keywords: Canada
Constitution
Law
Litterature
Metaphor
Narrative
Advisor: Weinrib, Lorraine E.
The Performance of Canadian History: The Work of Historical Interpreters, Animators, and Re-Enactors

Abstract This dissertation argues that living history is, in fact, a theatrical genre despite its practitioners’ insistence that it is not, and that this theatricality is a direct result of its originating from a well-funded, deeply-researched government program. Although there have been several significant studies about Canadian living history in the last thirty years, scholarship on living history is mostly American; therefore, I start with an assessment of the genesis, nomenclature, and literature of living history to clarify that both a theatrical and, critically, a Canadian perspective is missing from the field. Next, I analyze the uniquely Canadian living history tropes that arose from the development of the Louisbourg Method in the 1960s and use a scenographic and dramaturgical evaluation to codify the method’s innate theatricality. I further develop my theatrical assessment by discussing the paradoxical anti-theatricality of recreational re-enactors. Their rejection of theatricality not only robs them of a useful tool for telling historical stories, but also unintentionally re-enforces some of the more harmful aspects of re-enactment (war games for old white men) by rejecting creative ways to include non-canonical bodies and histories. Finally, I consider the uneasy alliance between living history and its various stakeholders in a discussion about the precarious position in which living history in Canada currently finds itself. Aspects of this problem include: untangling conflicting objectives arising from having multiple historical authorities at one site, co-opting living history methods to sell non-historical commodities, and reliance on commercialism to generate income. I conclude that the positive implications of living history performances are undone when the support of research and development, an original tenet of the Louisbourg Method, disappears. The lack of resources has led to a greater reliance on mismatched sponsorships and non-historical but crowd-pleasing activities which dilute or even threaten the performance and reception of Canadian history.

Keywords: Canada
historical interpretation
living history museums
museum theatre
public history
re-enactment
Advisor: Copeland, Nancy
Improving Out-of-hospital Cardiac Arrest Outcomes and Automated External Defibrillator Placement Guidelines through Optimization and Predictive Modeling

Out-of-hospital cardiac arrest (OHCA) is an often fatal, time-sensitive emergency event. OHCA survival decreases significantly for every minute without treatment. Defibrillation, an effective means to resuscitate OHCA victims, can be safely delivered by untrained bystanders using an automated external defibrillator (AED). The dissemination of AEDs in public areas for bystander use has been shown to reduce the time to defibrillation and triple OHCA survival. However, bystander AED use and OHCA survival remain low despite the increasing amount of resources dedicated to AED placement. Identifying the limitations of existing AED network design and exploring new strategies for AED deployment are crucial to ensure efforts and resources spent on AED placements directly translate to improved OHCA outcomes. To address these questions, this thesis focuses on increasing the understanding of spatiotemporal OHCA risk and developing novel tools to improve the assessment and design of AED networks, using optimization and machine learning techniques, with the ultimate goal of increasing bystander AED use and OHCA survival. Specifically, we analyzed AED placement guidelines, existing AED networks, bystander response records, and real OHCA patient data from Toronto, Canada, and Copenhagen, Denmark and identified limited temporal AED accessibility as a key factor responsible for low AED use rates. Motivated by this finding, we developed a spatiotemporal AED placement optimization model that maximizes spatial and temporal AED accessibility. We showed our model reverses the effects of limited temporal AED accessibility in both Toronto and Copenhagen, two vastly different cities with distinct geographies, populations, and EMS systems. This demonstrated the effectiveness and generalizability of our optimization approach. To validate the clinical value of our optimization model, we developed a novel in silico trial framework that computationally evaluates AED networks in a real-life deployment situation. Using this framework, we conducted two in silico trials and established the superiority of optimization approaches to current practices and established placement guidelines, which represent the gold standard of evidence-based AED placement recommendations, in improving estimated OHCA outcomes. In conclusion, our findings identify the importance of temporal AED accessibility, data-driven AED placement optimization models, and centralized decision making in improving AED use and OHCA survival.

Keywords: Automated External Defibrillator
Emergency Medical Services
Machine Learning
Optimization
Out-of-Hospital Cardiac Arrest
Public Health
Advisor: Chan, Timothy C.Y.
Anti-CRISPRs and CRISPR-Cas: Characterization and Biotechnology

Abstract Bacteria and phages (bacterial specific viruses) have been undergoing an evolutionary arms race for billions of years, whereby bacteria evolve mechanisms to inhibit phage infection and phages evolve mechanisms to evade bacterial defenses. Consequently, there are several mechanisms used by bacteria to inhibit phage infection. These include inhibiting phage adsorption, restriction modification systems, and the more recently discovered CRISPR-Cas immune systems. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci together with their accompanying CRISPR-associated (Cas) genes form the only known bacterial adaptive defense mechanism that effectively protects against the transfer of mobile genetic elements (MGEs) such as bacteriophages. CRISPR-Cas systems use an RNA-guided nuclease to bind and cleave foreign DNA, presenting a powerful barrier to phage infection. This strong evolutionary barrier led phages to evolve small protein inhibitors of CRISPR-Cas called anti-CRISPRs. In the first section of my work, I characterize the structure, function, and mechanism of action for an anti-CRISPR that inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa strain 4386. I show that beyond simply inhibiting the CRISPR-Cas system, anti-CRISPR AcrIE2 converts the CRISPR-Cas system from a DNA degradation complex to a transcriptional regulator. This modification suggests that anti-CRISPR proteins may function to do more than simply inhibit CRISPR-Cas targeting. Although CRISPR-Cas systems are a manifestation of the evolutionary arms race between bacteria and phages, CRISPR-Cas systems have also been used for genome editing in various organisms for research purposes. Considering this previous work, I developed a type I-E and type II-A CRISPR-Cas genome editing system to manipulate the genome of different P. aeruginosa strains for research. In the second section of my work, I discuss the methods I developed to efficiently edit the genome of P. aeruginosa. My work on genome editing in P. aeruginosa has and will allow for the development of new P. aeruginosa mutants for research purposes. Collectively, my work provides insight into the evolutionary interactions between phages and bacteria in the context of CRISPR-Cas and anti-CRISPRs. Moreover, it provides a genome editing tool for future P. aeruginosa studies.

Keywords: Anti-CRISPR
Bacteriophages
CRISPR-Cas
Gene regulation
Genome editing
Advisor: Davidson, Alan R
The Structure of Alkali Silicate Glasses and Melts: A Multi-spectroscopic Approach

The structure of alkali silicate glasses and melts is investigated using a multi-spectroscopic approach. Raman spectroscopy is used to characterize the local to intermediate range order within the glasses. We show that the distribution of rings varies as a function of composition, with 3-membered rings gaining importance with increasing alkali content. We apply a newly developed model for the tting of the high frequency envelope related to SiO4 symmetric stretch vibrations of Qn species. These ts are interpreted using the idea of modifier bound bridging oxygen. The proportions of the different Qn species vary with alkali concentration with Q4 species breaking down to form lower order Qn species with increasing alkali content. The Q2 peak appears at increasingly higher concentrations of M2O with increasing cation size. This leads us to believe that cations with a higher charge density cluster more readily than cations with a lower charge density. At the 20 mol. % composition we see a change in the silicate network, as shown by the absence of a Q4 peak and the proportion of 3-membered rings. The unique behaviour of lithium was investigated using X-ray absorption near-edge structure spectroscopy. We conducted experiments on a variety of lithium-bearing salts, minerals and glasses (LS: lithium silicate and LMS: lithium alkaline-earth silicate glasses) in order to characterize the lithium bonding environment. The Li K-edge position depends on the electronegativity of the element to which it is bound. The intensity of the first peak varies, depending on the existence of a 2p electron and can be used to evaluate the degree of ionicity of the bond. Crystalline lithium metasilicate has a sharp, strong intensity absorption edge whereas the lithium silicate glasses all have a weak intensity edge feature, similar to that of lithium carbonate. The area of the absorption edge peak increases with the lithium content of the LS glasses. The LMS glasses edge peak changes drastically depending on the alkaline-earth present. The peak area of the LMS glasses decreases with increasing charge density from barium to magnesium. We believe that the presence of Mg leads to more covalent-like Li-O bonds.

Keywords: alkali silicates
atomic structure
glasses
Raman spectroscopy
X-ray absorption spectroscopy
Advisor: Henderson, Grant S
Polars Africains et Enjeux de Justice

Cette thèse traite des enjeux de justice dans la fiction criminelle en Afrique subsaharienne francophone. Elle examine plus précisément les questions terminologiques (1), les problématiques inhérentes à la nouvelle criminelle (2), le caractère participatif de la criminalité en postcolonie (3) et la concurrence de légitimité à laquelle se livrent justice d’État et entités non étatiques (4). La nature protéiforme de la fiction criminelle a conduit les critiques à une certaine généralisation terminologique. Voilà pourquoi, dès le premier chapitre, la thèse questionne des expressions telles que « roman policier » aujourd’hui considérées comme des évidences alors qu’elles ne tracent pas toujours efficacement les contours d’une littérature qui n’a jamais dérogé à son engagement à dire le crime, mais qui s’est si souvent éloignée de la police. L’expression « roman policier » fait en plus l’impasse sur l’existence au sein de la fiction criminelle, en Afrique notamment, d’un important corpus de nouvelles criminelles qui traitent des questions sociétales avec une efficacité qui n’est en la matière pas celle du roman criminel. C’est la raison pour laquelle le deuxième chapitre est consacré à la nouvelle criminelle. Le troisième chapitre utilise le néologisme criminofiction (fiction criminogène) pour établir le fait que l’environnement postcolonial secrète le crime en abondance et contraint de ce fait les personnages à la violation des lois. Cette abondante criminalité débouche sur une concurrence de légitimité entre un État postcolonial délinquant et des individus – ou des entités non étatiques – auxquels les populations font appel. Des exemples de vengeance pure et de vindicte populaire se multiplient dès lors, comme le montre le quatrième chapitre. En définitive, la thèse établit que dans la fiction criminelle postcoloniale la justice s’émancipe des canons de légitimité en vigueur dans le droit dit positif, ces canons qui sont également à l’œuvre en métropole.

Keywords: Crime
Fiction
Justice
Polar
Polarovelle
Policier
Advisor: Tcheuyap, Alexie
Unbiased Proteomic and Genomic Approaches to Identify Novel Interactors of Wnt-βcatenin Signalling Pathway Members

The Wnt/βcatenin signalling pathway is an evolutionarily conserved signalling pathway crucial for development and adult tissue homeostasis. Mutations in pathway members occur often in various human diseases including cancer. Wnt ligands bind cell surface receptors, Frizzleds, which may result in pathway activation via βcatenindependent signalling and gene transcription. The Wnt/βcatenin pathway has been studied extensively, yet questions remain regarding its pathway members and their functions. βTrCP is an E3 ligase that acts in concert with the destruction complex to degrade βcatenin. To probe βTrCP function, we applied an affinity-purification coupled with mass spectrometry to identify novel substrates of βTrCP. We found that βTrCP targets several proteins for proteasomal degradation and characterized PPP1R15B which is a phosphatase involved in preventing transcription during ER stress. We demonstrate that Bio-ID is especially useful in determining elusive E3-substrate interactions. In a second study, we identified a novel member of the Wnt/βcatenin using a positive selection screen based on the LEF/Tcf binding elements driving an inducible apoptotic reporter coupled with a genome-wide CRISPR/Cas9 library. We identified IPO11 (importin-β11) as a novel gene required for Wnt/βcatenin signalling. Using biochemical and genetic approaches we demonstrate that importin-β11 is required for βcatenin nuclear localization in colorectal cancer cells and therefore their viability in 2D cell culture and 3D patient derived organoids.

Advisor: Angers, Stephane