VictorJuiz/thesis huggingface dataset:
Evolvable Mathematical Models: A New Artificial Intelligence Paradigm

We develop a novel Artificial Intelligence paradigm to generate autonomously artificial agents as mathematical models of behaviour. Agent/environment inputs are mapped to agent outputs via equation trees which are evolved in a manner similar to Symbolic Regression in Genetic Programming. Equations are comprised of only the four basic mathematical operators, addition, subtraction, multiplication and division, as well as input and output variables and constants. From these operations, equations can be constructed that approximate any analytic function. These Evolvable Mathematical Models (EMMs) are tested and compared to their Artificial Neural Network (ANN) counterparts on two benchmarking tasks: the double-pole balancing without velocity information benchmark and the challenging discrete Double-T Maze experiments with homing. The results from these experiments show that EMMs are capable of solving tasks typically solved by ANNs, and that they have the ability to produce agents that demonstrate learning behaviours. To further explore the capabilities of EMMs, as well as to investigate the evolutionary origins of communication, we develop

Keywords: Artificial Intelligence
Artificial Life
Evolutionary Computation
Evolutionary Robotics
Genetic Programming
Advisor: Gabriele, M.T. D'Eleuterio
Toward a Typology of Semantic Transparency: The Case of French Compounds

This thesis proposes an extension to existing models of semantic transparency in compounding by incorporating previously unexplored features into the concept. Although the term semantic transparency is widely used in research on multi-word lexemes, the concept is often viewed as simply a matter of semantic compositionality, which is to say that transparency is determined solely by the meaning of individual constituents. While this approach offers a number of advantages, it is nevertheless insufficient on two accounts: one, it groups together a number of compositional compounds that are otherwise semantically distinct (e.g. ice breaker ~ ice cube ~ ice age), and two, it offers no clear means to order or rank partially compositional compounds (e.g. firefly ~ butterfly ~ barfly). This thesis therefore argues for a more holistic approach to semantic transparency, one that views the phenomenon as both scalar and multi-faceted, the result of which is a more granular model capable of further distinguishing between several different compound types.The typology of semantic transparency of compounds proposed in this work consists of four basic factors supported by a dataset consisting of more than 1,000 French NN and N Ă  N compounds extracted from Wiktionary. The first factor, headedness, touches on features pertaining to a compound's semantic head, for which concepts such as canonical position and strong/weak centricity are advanced. Second, compositionality is formalized according to a four-way configuration based on how individual constituents contribute meaning to the whole. The third factor, semantic homogeneity, relates to the degree of shared meaning between analogically similar compounds. Finally, the implicit semantic relations within compounds are explored. Consequently, fifteen basic associations are proposed and evaluated using the compound data collected from Wiktionary. Together, these four factors yield a typology involving sixteen possible transparency profiles, each of which is ordered according to the relative weight of its semantic features. It is believed that this typology offers a far richer conceptual space within which to further the discussion of semantic transparency as it pertains to complex constructions such as compounds.

Keywords: compounds
french
morphology
semantics
semantic transparency
Advisor: Anne-Marie, Brousseau
Language Attitudes towards Canadian French and English, 1691-1902: The Emergence of the Canadian Voices

This dissertation examines the origins and development of attitudes (in the guise of beliefs and stereotypes) towards Canadian French and Canadian English during the 18th and 19th centuries, as expressed primarily by foreign travellers to North America. By conducting a comparative study of these two languages, a bridge is built between French Canadian studies on Canadian French, and Anglophone Canadian studies on Canadian English, two fields which have historically been distinct and separate.The time period under study (1691-1902) is marked by major political and social changes (e.g., the English Conquest, the Confederation), all of which had major, lasting effects on the development and status of both languages. In order to study the evolution of language attitudes during this period, I used content analysis on the metalinguistic commentary found in a wide variety of texts, including travel journals, scholarly and newspaper articles, monographs, and prescriptive texts, written in French and English.My analysis shows that British commentators were the most critical of both languages (and peoples), and relied almost entirely on beliefs and stereotypes rather than empirical evidence to support their claims. As colonial peoples in the process of renegotiating their linguistic and cultural identities, French and British Canadians were strongly affected by these beliefs, particularly following Confederation. From this point forward, we see evidence for what I have termed the "Emergence of the Canadian Voices" that is, Canadians' rejection of foreign opinion about their language and culture, and a move towards an endogenous linguistic norm, which was supported by the increasing use of linguistic studies on both languages. Examining how these "Canadian Voices" developed provides an important insight into the politically charged discourse about the French and English languages in the late 19th century, and is essential for understanding the complex and fiercely debated language question in Canada today.

Keywords: Canadian History
English Language
Folk Linguistics
French Language
Language Attitudes
Stereotypes
Advisor: Anne-Marie, Brousseau
Striatal Mechanisms Mediating Parkinsonism and L-DOPA Induced Dyskinesia: Contribution of the Direct - and Indirect - Output Pathways

L-DOPA (L-3,4-dihydroxyphenylanalnine) therapy is indispensible in the treatment of Parkinson's disease (PD) motor symptoms, but the use of these drugs is plagued by the development of major side effects termed L-DOPA-induced dyskinesia (LID). Smooth motor performance results from the balanced influence of these pathways on the neural activity of the basal ganglia output structures. The prevailing view of PD, and LID etiology is tightly associated with a putative interference in the democracy between these two pathways. Due to the lack of appropriate animal models, to date, this theory has not been directly proven. To circumvent these issues models of PD and LID were developed in bacterial artificial chromosome (BAC) mice, which selectively tag neurons of the direct- and indirect-pathways with enhanced green fluorescence protein (eGFP). By using these models is was possible to characterize how chronically perturbed striatal dopamine transmission drives an imbalance in through changes in short- and long-term properties of direct and indirect corticostriatal synapses. Following striatal dopamine depletion, indirect pathway neurons exhibited abnormal short-term changes, showing decreased levels of paired pulse facilitation, enhanced sensitivity to presynaptic stimulation and an increase in the relative contribution of NMDAR to the EPSC but no change in spontaneous synaptic activity. While, in the direct pathway, firing threshold was reduced, spike frequency adaptation developed and the frequency of spontaneous activity was also reduced. In addition, changes in the properties of NMDAR kinetics suggest that these receptors were desensitized. Long-term abnormalities in the direct and indirect striatal output pathways were examined in models of parkinsonism and dyskinesia. Thus in parkinsonism the indirect pathway exhibits only long-term potentiation (LTP), providing a basis for its over-activity, while the direct pathway, exhibits only long-term depression (LTD) will become underactive. By contrast, in the dyskinetic state, the direct pathway exhibits only LTP, becoming generally overactive, and the indirect pathway exhibits only LTD. These findings explain some of the positive effects and motor complications elicited by L-DOPA and offer firm observations on the role of the direct- and indirect-pathway in basal ganglia circuitry abnormalities in LID and PD.

Keywords: Direct pathway
Indirect pathway
L-DOPA-induced dyskinesia
Parkinson's disease
Striatum
Synaptic plasticity
Advisor: Joanne, E Nash
Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely available technologies and thus can potentially improve local control for liver cancer patients receiving radiotherapy.

Keywords: Deformable image registration
Dosimetry
Finite element analysis
Liver cancer
Radiation oncology
Advisor: Kristy, K Brock
Determining the Mechanisms of Resistance to Drug Combinations and their Fitness Effects in Candida albicans

The evolution of drug resistance is occurring rapidly and threatening our arsenal of antimicrobials. This is a poignant issue with antifungals, whose targets are limited due to conservation between fungi and the human host. A promising strategy is to enhance effectiveness of our current antifungals using combination therapy. Adding an inhibitor of one of the key stress response proteins, Hsp90 or calcineurin, to an antifungal azole renders the activity of the azole fungicidal and abrogates azole resistance. However, evidence from clinical isolates indicates that resistance to the drug combination can still arise. Determining the mechanisms of resistance to these drug combinations and their fitness effects will provide information about how resistance can occur and whether it is likely to spread in a population. To address what mechanisms of resistance can arise to drug combinations, I evolved strains of the leading fungal pathogen, Candida albicans, and its genetically tractable relative Saccharomyces cerevisiae, in the presence of an azole and the Hsp90 inhibitor geldanamycin (GdA) or the calcineurin inhibitor FK506. The vast majority of strains (286) went extinct, however, I identified and validated mechanisms of resistance in 13 strains. A variety of resistance mechanisms were found, from well-established resistance mechanisms to novel ones. To address the fitness effects of resistance to an azole in combination with GdA or FK506, I took advantage of these C. albicans in vitro evolved strains and a series of C. albicans clinical isolates that transition to Hsp90- and calcineurin-independent azole resistance. I determined that resistance to the drug combination is often but not universally costly in the absence of drug and in novel, clinically relevant stress environments. Together these results provide a basis for our understanding of key parameters for the evolution of resistance to drug combinations: the variety of mechanisms that encompass resistance, and their fitness costs.

Advisor: Leah, E Cowen
On the Structure of Nuclear C*-algebras with Real Rank Zero

In this thesis, we study three main problems: characterising approximation properties in terms of coverings by finite dimensional subalgebras; generalising results about projections to results about positive elements; and classifying locally liftable C*-algebras with finite covering dimension.Nuclear dimension and decomposition rank are important regularity properties often described as ``noncommutative covering dimensions". We characterise these properties for C*-algebras with real rank zero in a way that perhaps fits this description more clearly: the dimension is less than n if, and only if, there exist n+1 finite dimensional subalgebras that cover the C*-algebra in an appropriate way. We show that general nuclear C*-algebras with real rank zero admit a similar covering, although their covering dimension may be infinite.Finite decomposition rank is a strictly stronger property than finite nuclear dimension (for example, many purely infinite C*-algebras have infinite decomposition rank but finite nuclear dimension). From our characterisations, we see that the main differences between the two concepts relate to questions about positive elements vs.~projections, and approximately commuting elements vs.~being close to elements that exactly commute. In the fourth chapter, we use these differences to modify results of Winter so that the assumption of finite decomposition rank can be relaxed to finite nuclear dimension.Another important concept in the study of the structure of C*-algebras is semiprojectivity, which has proved to be a useful tool in the classification program, and Blackadar has asked if every separable C*-algebra is an inductive limit of semiprojective C*-algebras. Motivated by this (and our characterisation of decomposition rank) we look at various local lifting properties that are possessed by many C*-algebras and allow results about decomposition rank to be generalised to results about nuclear dimension. Specifically, we show that simple, separable, unital, finite, nonelementary C*-algebras with finite nuclear dimension, real rank zero and finitely many extremal traces, which are also locally liftable (in a suitable sense) and satisfy the Universal Coefficient Theorem are classifiable.

Advisor: George, A Elliott
Adverse Nephrotoxic Events in Critically Ill Children: A Pharmacoepidemiologic Evaluation

Background: Kidney injury is a common adverse event in critically ill children and has a complex and multifactorial etiology. Some factors, such as age and sex, are non-modifiable while others, including medication exposure, are modifiable and present an opportunity to decrease the risk of kidney injury. The objective of this dissertation was to quantify the risk of acute kidney injury (AKI) attributable to the initiation of nephrotoxic medications among critically ill children.Methods: We utilized a pharmacoepidemiologic approach, using AKI as a model for studying adverse drug events (ADEs) in children. First, we conducted a systematic review of the application of an accepted definition of AKI (the RIFLE criteria) in children. Second, we estimated the incidence and associated factors of AKI in a 3.5-year cohort of critically ill children. Finally, we conducted a nested case-control study to quantify the risk of developing AKI after the initiation of one or more nephrotoxic medications.Results: Our systematic review identified wide variation in the application of the RIFLE. We found an AKI incidence of 23.7% in our patient population and identified patients at increased risk for the development of AKI. Administration of nephrotoxic medications during ICU admission was the single greatest risk factor for AKI. We found a high incidence of nephrotoxic medication use in the ICU; over 80% of patients were exposed to one or more nephrotoxic medications. The administration of ganciclovir, furosemide and gentamicin were significantly associated with increased odds of developing AKI before and after adjustment for underlying differences in risk factors of AKI.Conclusion: Acute kidney injury is common among critically ill children. Nephrotoxic medication exposure preceding AKI is common. The results of this work can help to optimize prescribing and aid clinicians in making optimal treatment choices, reducing harm and improving patient outcomes.

Advisor: Christopher, S Parshuram
Insights into the Mechanism of Drug-induced Agranulocytosis: A Study of the Immune Changes Induced by Clozapine and Amodiaquine

Drug-induced agranulocytosis is an idiosyncratic adverse drug reaction, and although its mechanism is not well understood, it is suspected to involve both metabolic (reactive metabolites) and immune components. Numerous drugs that cause agranulocytosis are metabolized to reactive species by neutrophils that, in turn, covalently bind to the cells; a process hypothesized to be dependent on neutrophil myeloperoxidase. However, despite extensive in vitro studies, in vivo evidence to support this is lacking. Therefore, the first goal of these studies was to characterize the involvement of myeloperoxidase in the covalent binding of amodiaquine and clozapine to neutrophils. In myeloperoxidase knockout mice treated with amodiaquine, covalent binding to neutrophils was found to decrease 2-fold compared to control. Interestingly, lack of the enzyme did not completely abolish binding, and lymphocytes were also found to extensively bind the drug. These studies confirm that myeloperoxidase is responsible for some of the covalent binding to neutrophils, but that other pathways not yet defined in neutrophils, as well as other cells, are also capable of oxidizing amodiaquine. The second goal of this work was to investigate the immune component associated with drug-induced agranulocytosis by studying the response of neutrophils and the overall immune system to clozapine. Due to difficulties accessing patients, these studies were pursued by first designing a rat model of early clozapine treatment. Using this model, the response of neutrophils to clozapine was found to reflect that of G-CSF-mediated stimulation of the bone marrow. A proinflammatory response to clozapine was detected in the rats, characterized by neutrophilia and elevated levels of the acute phase protein -1-acid glycoprotein, which led us to investigate the ability of clozapine to activate inflammasomes. These studies led to the proposal of a novel hypothesis, specifically, that the proinflammatory response to clozapine at the start of treatment is mediated by inflammasome-generated IL-1.

Keywords: Adverse drug reactions
Agranulocytosis
Amodiaquine
Clozapine
Toxicology
Advisor: Jack, Uetrecht
Clinical Supervision and Learning in Acute Care Environments: A Multifaceted Relationship

ContextClinical supervision is intended to maintain a balance between a safe and timely provision of care to the patients and the creation of learning opportunities for the trainees. Many changes have recently affected the health care and medical education systems. The effects of these changes on current supervisory practices and on clinical learning are only partially understood. The objective of this program of research was therefore to explore the complex relationships between clinical supervision and learning in today's acute care environments.DesignTwo studies were combined: a mixed methods, simulation-based study, followed by an observational, naturalistic study. For the simulation study, 53 residents were randomized to one of three levels of clinical supervision and completed acute simulated scenarios. This study explored the impact of the level of clinical supervision on quantitative outcomes related to patient care and trainee learning, and on the learning processes involved in acute resuscitation. The second study, based on 350 hours of participant observation in real acute care environments, explored three aspects of the learning interactions among supervisors and trainees.ResultsThe simulation study indicated a benefit of direct supervision for patient care. Direct supervision had a neutral effect on learning, despite the creation of distinct learning opportunities. In real acute clinical environments, learning interactions between clinical supervisors and trainees facilitated trainee involvement in patient care and allowed supervisors to adjust the level of supervision. Factors related to the clinical case, the participants, and the broader context interacted to affect the occurrence of these learning interactions. In addition, the specific clinical situations in which participants interacted affected the nature and the educational potential of the learning interactions. ConclusionThis program of research revealed that direct supervision could improve patient care without compromising trainee learning. In-person interactions between clinical supervisors and trainees were commonly used to create learning opportunities in today's acute clinical environments. Clinical supervisors and trainees displayed different types of learning interactions in response to different clinical circumstances.

Keywords: Clinical learning
Clinical supervision
Critical care
Advisor: Vicki, R LeBlanc