VictorJuiz/thesis huggingface dataset:
1H NMR Metabolomics of Earthworm Responses to Sub-lethal Polycyclic Aromatic Hydrocarbon Exposure

1H nuclear magnetic resonance (NMR) metabolomics was used to determine the response of earthworm exposure to polycyclic aromatic hydrocarbons (PAHs) in contact and soil tests. Eisenia fetida is recommended for toxicology testing, but to date this species has not frequently been used in environmental metabolomic studies. The metabolic profile of E. fetida was characterized with the goal of using this species in metabolomic studies. Testing several individual solvents for earthworm tissue extraction indicated that D2O buffer extracted the highest concentration of the widest variety of earthworm metabolites. Sample preparation methods were evaluated to reduce variability and achieve reproducible control groups for use in metabolomic studies. 96h depuration and intact lyophilization of earthworms before homogenization resulted in the least variation between sample extracts. This sample preparation method was used to compare E. fetida and two other earthworm species (Lumbricus rubellus and Lumbricus terrestris) and E. fetida had the most reproducible 1H NMR spectra. E. fetida was then used to identify the metabolic response after exposure to several concentrations of the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene and pyrene, individually and in mixtures. With exposure to individual PAHs in contact tests, earthworm responses were both PAH- and concentration- dependent. In earthworms exposed to PAH mixtures in contact tests, an increase in amino acids was measured. Furthermore, an increase in specific amino acids and a decrease in maltose were identified as potential indicators of sub-lethal phenanthrene exposure in soil. Lastly, the relationship between earthworm response and contaminant bioavailability in soil was tested. Contaminant bioavailability is typically assessed using indirect methods [e.g., ‘soft’ extraction techniques like hydroxypropyl cyclodextrin (HPCD) extraction]. However, it was found that the directly measured response of earthworm exposure to sub-lethal concentrations of phenanthrene in soil is related to both the total and bioavailable phenanthrene. This suggests there is potential for the use of 1H NMR metabolomics for the assessment of contaminant bioavailability. This thesis has demonstrated that E. fetida are suitable for metabolomic studies and has indicated that 1H NMR metabolomics may have potential for measuring and monitoring earthworm exposure to sub-lethal concentrations of PAHs.

Keywords: Metabolomics
1H NMR
Advisor: Simpson, Myrna J.
Patient Preferences, Referral Practices, and Surgeon Enthusiasm for Degenerative Lumbar Spinal Surgery

Degenerative disease of the lumbar spine (DDLS) is a common condition for which surgery is beneficial in selected patients. Wide variation in surgical referral and rates of surgery has been observed contributing to unequal access to care. Our objectives were to examine (1) the variation in preferences for referral and surgery among surgeons, family physicians (FPs) and patients, (2) how FP referral practices compare with preferences and guideline recommendations, and (3) how the ‘enthusiasm’ of patients and physicians influence regional variation in surgical rates. We used conjoint analysis in a mailed survey to elicit preferences based on clinical vignettes from surgeons, FPs and patients. A Delphi expert panel provided consensus guideline recommendations for surgical referral to compare with actual FP referral practices. Rates of surgery for DDLS, obtained from Ontario hospital discharge data, were used to quantify regional variation and regression models assessed the relationship with patient and physician enthusiasm. We identified significant differences in preferences for referral and surgery between patients, FPs and surgeons. Surgeons placed high importance on leg-dominant symptoms while patients had high importance for quality of life symptoms (i.e. severity, duration, walking tolerance). Surgical referral practices were poorly predicted by individual FP preferences and guideline recommendations based on clinical factors alone. Variation in Ontario surgical rates was higher than that of hip or knee replacements and was highly associated with the enthusiasm of surgeons (p<0.008), rather than FPs or patients. By appreciating the variation in preferences between patients and physicians, and exploring other non-clinical factors that influence referrals, we may be able to improve the efficiency of referrals and enhance the shared decision making process. With an understanding of the influence that surgeons have in driving variation in surgical rates, further research may allow us to direct strategies to improve access and allow for a more equitable delivery of care for patients suffering from DDLS.

Keywords: spinal surgery
patient preferences
physician preferences
regional variation
Advisor: Wright, James G.
Effective Search Techniques for Non-classical Planning via Reformulation

Automated planning is a branch of AI that addresses the problem of generating a course of action to achieve a specified objective, given an initial state of the world. It is an area that is central to the development of intelligent agents and autonomous robots. In the last decade, automated planning has seen significant progress in terms of scalability, much of it achieved by the development of heuristic search approaches. Many of these advances, are only immediately applicable to so-called classical planning tasks. However, there are compelling applications of planning that are non-classical. An example is the problem of web service composition, in which the objective is to automatically compose web artifacts to achieve the objective of a human user. In doing so, not only the hard goals but also the \emph{preferences} of the user---which are usually not considered in the classical model---must be considered. % Also, the automated composition %should deal with abstract representations of the web %artifacts---which may also not adjust to the classical model. In this thesis we show that many of the most successful advances in classical planning can be leveraged for solving compelling non-classical problems. In particular, we focus on the following non-classical planning problems: planning with temporally extended goals; planning with rich, temporally extended preferences; planning with procedural control, and planning with procedural programs that can sense the environment. We show that to efficiently solve these problems we can use a common approach: reformulation. For each of these planning tasks, we propose a reformulation algorithm that generates another, arguably simpler instance. Then, if necessary, we adapt existing techniques to make the reformulated instance solvable efficiently. In particular, we show that both the problems of planning with temporally extended goals and with procedural control can be mapped into classical planning. Planning with rich user preferences, even after reformulation, cannot be mapped into classical planning and thus we develop specialized heuristics, based on existing heuristics, together with a branch-and-bound algorithm. Finally, for the problem of planning with programs that sense, we show that under certain conditions programs can be reduced to simple operators, enabling the use of a variety of existing planners. In all cases, we show experimentally that the reformulated problems can be solved effectively by either existing planners or by our adapted planners, outperforming previous approaches.

Keywords: artificial intelligence
automated planning
temporally extended goals
preferences
golog
Advisor: McIlraith, Sheila Ann
Synaptic Plasticity Induced Through CP-AMPARs is Dependent on the ERK/MAPK Signalling Cascade

Recent literature has shown that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors lacking the GluR2 subunit (thus calcium permeable) are widely expressed in the CNS, especially in interneurons and glia, where they contribute to synaptic transmission and plasticity. Studies have also indicated that calcium permeable AMPARs (CP-AMPARs) are expressed and participate in synaptic regulation in principal neurons, including hippocampal pyramidal neurons. Furthermore, CP-AMPARs and their resultant calcium influx are implicated in various pathophysiological conditions such as ischemia and seizures. However, the synaptic events activated by calcium influx through CP-AMPARs remain unknown. I took advantage of genetically altered mice without (GluR2-/-) or with reduced GluR2 (GluR2+/-), thus allowing the expression and detailed analysis of synaptic CP-AMPARs in hippocampal pyramidal neurons. Utilizing electrophysiological techniques, I demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR-dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor (NMDAR) independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460. Surprisingly, calcium/calmodulin-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDAR-dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR-dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDAR dependent LTP in control studies. In contrast, inhibitors for the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Additional studies with knockout mice revealed that the ERK/MAPK signalling cascade is likely acting through p-21 activated kinase 1 (or PAK1, a Rho-GTPase associated kinase) dependent mechanisms. These results suggest that distinct synaptic signalling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain.

Keywords: Synaptic plasticity
AMPA receptors
Calcium signalling
ERK/MAPK
LTP
CaMKII
GluR2
PI3K
Ras
L-LTP
protein synthesis
hippocampus
CA1
memory
ischemia
addiction
seizure
PAK1
ROCK2
calcium pemeable AMPA receptors
NMDA receptors
electrophysiology
knockout mice
Western Blot
Advisor: Jia, Zhengping
The Aging Workforce: Addressing its Challenges Through Development of a Dignified Lives Approach to Equality

Against the background of the global demographic shift towards an aging workforce and its impacts on the labour market and the economy in industrialized societies, this dissertation pinpoints six salient challenges for future litigation and policy-making in the area of labour and employment discrimination law. These include the global tendency towards abolishing mandatory retirement and increasing the eligibility age for pension benefits; legislative age-based distinctions; cost as a justification for age discrimination; performance appraisals of senior workers; and the duty to accommodate senior workers. At the core of each challenge lies a normative question regarding our conception of senior workers’ right to age equality, its importance and relative weight compared with other rights and interests. The aim of this dissertation is therefore to critically review the current understanding of this right and its moral and economic underpinning. Most notably, the dissertation contends that the prevailing conception of equality assessment (the Complete Lives Approach to equality), according to which equality should be assessed based on a comparison of the total share of resources obtained by individuals over a lifetime, has substantial implications for age discrimination discourse. As it uncovers the numerous difficulties with the complete lives approach, the dissertation develops an alternative: the Dignified Lives Approach to equality, according to which an individual should be treated with equal concern and respect, at any particular time and regardless of any comparison. The dissertation then articulates five essential principles founded in Dworkin’s notion of equal concern and respect: the principle of individual assessment, the principle of equal influence, the principle of sufficiency, the principle of social inclusion, and the principle of autonomy. When one of these principles is not respected at any particular time, a wrong is done, and the right to equality is violated. Next, the dissertation elucidates when and why unequal treatment of senior workers based on age does not respect each of these five principles and therefore constitutes unjust age discrimination. It demonstrates that senior workers’ right to age equality is a fundamental human right. Finally, it examines the above-mentioned challenges through the lens of the new Dignified Lives approach.

Keywords: Law
Labour Law
Employment Law
Labour Policy
Discrimination Law
aging workforce
senior workers
accommodation
mandatory retirement
age discrimination
theories of equality
equality sssessment
Advisor: Macklem, Patrick
Taking a Risk: Does Human Capital Investment Pay Off for Educationally Disadvantaged Adults?

Although human capital investment is often proposed as a solution to improve the labour market prospects of individuals who reach adulthood without obtaining a post-secondary credential, little is known about whether skills upgrading actually pays off. Using three national cross-sectional surveys on adult education as well as longitudinal data from the Panel Survey of Income Dynamics (1992-2005), I analyze how returning to school affects the earnings trajectories of men and women who enter the labour force with low levels of initial education. There are two major findings related to the earnings and advancement question. First, although both Canadian and American adults with low levels of initial education are significantly less likely than their more educated counterparts to participate in education and training, when they do participate, they are more likely to report it helped them increase their earnings. Second, these perceived gains are matched by substantial gains in actual earning growth. While the opportunity cost of returning to school is quite high – returnees experience a sharp drop in annual earnings during the years while they are in school – for both women and men, this investment yields a significant increase in earnings in the post schooling period. In addition, I address the question of why – if the earnings gains are so substantial – do so few less educated adults return to school? There are three key findings related to the participation question. First, even after accounting for a rich set of covariates, the effects of family of origin socio-economic status on educational attainment persist over the life course. Second, despite these enduring effects, current family and labour market dynamics matter as well. Consistent with the human capital model, I find evidence that, educationally disadvantaged individuals return to school to improve their labour market prospects. Taken together these results demonstrate that at least for some educationally disadvantaged adults, human capital investment is an effective strategy for labour market advancement. This conclusion challenges the standard ‘cumulative disadvantage’ view of adult education as simply another mechanism that serves to reproduce inequality.

Keywords: adult education
labour markets
returns to education
participation
Advisor: Myles, John
L2 Learners’ Difficulties in the Interpretation of the Spanish Subjunctive: L1 Influence and Misanalysis of the Input

This study examines L2 learners’ difficulties in the acquisition of the Spanish subjunctive. In particular, it investigates the interpretations English-speaking L2 learners of Spanish assign to the subjunctive in temporal, concessive, and conditional clauses, where mood choice involves the interaction of morpho-syntactic, semantic, and pragmatic knowledge. In contrast to previous research that has given little attention to the difficulties L2 learners experience, this study hypothesizes they might be attributed to “input traps” resulting from L1 transfer of syntactic and semantic properties of the subjunctive adjuncts and misanalysis of the input due to the lack of integration of different types of information. This study tests this claim by comparing the grammars of English-speaking L2 learners of Spanish with those of native Spanish speakers. If L2 learners share similar patterns with L1 speakers in contexts where both languages behave similarly, and exhibit different patterns from L1 speakers in contexts where both languages behave differently, difficulties should be attributed to L1 influence on the L2. On the other hand, if L2 learners exhibit different patterns from L1 speakers in contexts where semantic or pragmatic features determine the use of the subjunctive, difficulties should be attributed to failures in form-meaning mappings. Data collection involved a Preference Task with three possible options: a sentence with the indicative, with the subjunctive, or no preference. Subjects were asked to select which of the three choices they preferred according to the context presented in the story. Twenty advanced English-speaking L2 learners of Spanish and twenty native speakers from different Spanish-speaking countries, who served as the control group, took part in this study. Results indicate that subjunctive adjuncts present difficulties in L2 acquisition even for advanced L2 learners. Although they exhibit sensitivity to certain subjunctive features and contextual meanings, data reveal that convergence and non-convergence were primarily determined by L1 influence on L2. Crucially, those features absent from the L1 give rise to greater efforts and difficulties in L2 form-meaning mappings of mood selection.

Keywords: L2 Acquisition
Spanish Subjunctive
Advisor: Perez-Leroux, Ana Teresa
A Perturbation-inspired Method of Generating Exact Solutions in General Relativity

General relativity has a small number of known, exact solutions which model astronomically relevant systems. These models are highly idealized situations. Either perturbation theory or numerical simulations are typically needed to produce more realistic models. Numerical simulations are time-consuming and suffer from a difficulty in interpreting the results. In addition, global properties of numerical solutions are nearly impossible to uncover. On the other hand, standard perturbation methods are very difficult to implement beyond the second order, which means they barely scratch the surface of non-linear phenomena which distinguishes general relativity from Newtonian gravity. This work develops a method of finding exact solutions, inspired by perturbation theory, which have energy-momentum tensor components that approximately satisfy desired relationships. We find a spherical lump of matter which has a density profile μ ∝ r–2 in a Robertson-Walker background; it looks like a galaxy in an expanding universe. We also find a plane-symmetric perturbation of a Bianchi type I metric with a density profile μ ∝ z–2; it models a jet impacting a sheet-like structure. The former solution involves a wormhole while the latter involves a two dimensional singularity. These are both nonlinear structures which perturbation theory can never produce.

Keywords: General Relativity
Exact solution
Cosmology
Perturbation
Astrophysics
Relativity
Advisor: Dyer, Charles C.
Abstraction for Verification and Refutation in Model Checking

Model checking is an automated technique for deciding whether a computer program satisfies a temporal property. Abstraction is the key to scaling model checking to industrial-sized problems, which approximates a large (or infinite) program by a smaller abstract model and lifts the model checking result over the abstract model back to the original program. In this thesis, we study abstraction in model checking based on \emph{exact-approximation}, which allows for verification and refutation of temporal properties within the same abstraction framework. Our work in this thesis is driven by problems from both practical and theoretical aspects of exact-approximation. We first address challenges of effectively applying symmetry reduction to \emph{virtually} symmetric programs. Symmetry reduction can be seen as a \emph{strong} exact-approximation technique, where a property holds on the original program if and only if it holds on the abstract model. In this thesis, we develop an efficient procedure for identifying virtual symmetry in programs. We also explore techniques for combining virtual symmetry with symbolic model checking. Our second study investigates model checking of \emph{recursive} programs. Previously, we have developed a software model checker for non-recursive programs based on exact-approximating predicate abstraction. In this thesis, we extend it to reachability and non-termination analysis of recursive programs. We propose a new program semantics that effectively removes call stacks while preserving reachability and non-termination. By doing this, we reduce recursive analysis to non-recursive one, which allows us to reuse existing abstract analysis in our software model checker to handle recursive programs. A variety of \emph{partial} transition systems have been proposed for construction of abstract models in exact-approximation. Our third study conducts a systematic analysis of them from both semantic and logical points of view. We analyze the connection between semantic and logical consistency of partial transition systems, compare the expressive power of different families of these formalisms, and discuss the precision of model checking over them. Abstraction based on exact-approximation uses a uniform framework to prove correctness and detect errors of computer programs. Our results in this thesis provide better understanding of this approach and extend its applicability in practice.

Keywords: Model Checking
Abstraction
Verification
Temporal Logic
Advisor: Chechik, Marsha