VictorJuiz/thesis huggingface dataset:
Reading Comprehension in English-French Bilinguals: The Roles of Syntactic and Morphological Awareness
Keywords: Bilingualism
Education
French immersion
Morphological Awareness
Reading Comprehension
Syntactic Awareness

This dissertation examines the roles of two types of metalinguistic awareness – syntactic and morphological awareness – in the reading comprehension of children enrolled in early Canadian French immersion programs. The first study investigated the contributions of syntactic awareness to concurrent reading comprehension within and across children’s first and second languages. Seventy-two emerging English-French bilingual children in Grade 3 completed measures of syntactic awareness, reading comprehension, word reading, and vocabulary in both languages, as well as a measure of nonverbal reasoning. Results revealed that French syntactic awareness made a significant unique contribution to French reading comprehension beyond controls. French syntactic awareness also contributed cross-linguistically to English reading comprehension after accounting for English controls, including English syntactic awareness. In contrast, no significant unique relations were found between English syntactic awareness and reading comprehension in either language beyond controls.The second study examined the development of morphological awareness, as well as its role in reading comprehension, in emerging English-French bilinguals. Using a longitudinal design, 115 participants were assessed in both languages on morphological awareness, reading comprehension, word reading, and vocabulary in Grade 2 and again in Grade 3. A measure of nonverbal reasoning was also collected. Results highlight the influence of phonological structure and cognate status on children’s development of morphological awareness in each language. Within-language results revealed that French morphological awareness contributed to concurrent French reading comprehension in both Grades 2 and 3 after controls, while English morphological awareness contributed to English reading comprehension in Grade 3 only. Longitudinally, Grade 2 morphological awareness predicted gains in Grade 3 reading comprehension within each language, beyond a stringent autoregressive control. Cross-language results indicated that French morphological awareness made significant contributions to English reading comprehension concurrently in Grade 3, and longitudinally from Grade 2 to Grade 3. In contrast, English morphological awareness did not contribute to French reading comprehension concurrently or longitudinally. Taken together, the findings of this dissertation add to our understanding of the roles of syntactic and morphological awareness in the reading comprehension of bilingual children. The findings underscore the importance of cultivating children’s metalinguistic awareness during the early stages of bilingual reading instruction.
Pre-velar /æ/-raising in Ontario and Colorado English: Production, Perception and Metalinguistic Awareness
Keywords: BAG-raising
Metalinguistic Awareness
North American English
Production-Perception Link
Speech Perception
Speech Production

Pre-velar /æ/-raising (BAG-raising) is a process in which some speakers of North Amer- ican English raise /æ/ before /g/, but not /k/. This process occurs in parts of Canada (e.g. Boberg, 2008), and in the Pacific Northwest (e.g. Freeman, 2021) and Upper Midwest (e.g. Koffi, 2013) in the US. While documentation of the production of BAG-raising is limited, less is known about its perception. Previous studies find no difference between how BAG-raisers and non-raisers perceive raising (Freeman, 2019; Sullivan, 2020a); however, anecdotal evidence suggests individuals from dialect regions without BAG-raising perceive the raised /æ/ in [æg] words as distinct from its unraised counterpart while those from BAG-raising regions do not. This dissertation seeks to establish if listeners hear raised and unraised /æ/ as distinct pronunciations, and if this is conditioned by production, metalinguistic awareness and/or phonological context. First, a metalinguistic awareness survey confirmed anecdotal evidence for differences in metalinguistic awareness between individuals from BAG-raising and non-raising regions. Individuals from non-raising regions had more metalinguistic awareness than those from BAG-raising regions. The study demonstrates that it may be possible to quantify metalinguistic awareness, though more work is needed to establish how best to do so, and which aspects of folk linguistic awareness (Preston, 1996) different tasks are tapping into. Next, a production study extended knowledge about the distribution of the production of BAG-raising to Colorado, where it has not been previously studied, and Ontario, where it has been studied, but not specifically targeted (Boberg, 2008; Sullivan, 2020a). This study showed that BAG-raising occurs in Ontario, but not Colorado. Finally, an AX discrimination task explored if speakers could discriminate raised and unraised /æ/ and if this was conditioned by their individual degree of BAG-raising, their metalinguistic awareness or the phonological context of /æ/. Listeners with higher degrees of BAG-raising discriminated raised and unraised /æ/ less than those with lower degrees of BAG-raising, but only before /g/, suggesting that production is implicated in perception and that mental representations are formed based on an individual’s production and the phonological context in which a sound occurs.
Fair Multi-resource Allocation for Mobile Edge Computing
Keywords: Fair Resource Allocation
Game Theory
Mechanism Design
Mobile Edge Computing

The problem of fair and efficient allocation of resources in Mobile Edge Computing (MEC) is of significant importance. Users in MEC, instead of utilizing the servers in the core network, can offload their tasks to the MEC-capable access points (APs) at the network's edge. Each user in MEC requires resources in a customized proportion to execute a task on a MEC server. Furthermore, The task input data and execution results are sent through shared wireless communication links to and from the MEC servers. Hence, MEC is characterized by allocating multiple communication and computation resources. Existing resource allocation rules generally consider Pareto Optimality (PO), Envy-Freeness (EF), Sharing Incentive (SI), and Strategy-Proofness (SP) as the most desirable fairness and efficiency properties. This dissertation proposes fair and efficient resource allocation mechanisms for three different MEC systems. We first consider the single-AP MEC systems, where the users must upload their tasks over a dedicated wireless communication link outside the computing servers. We propose a fair multi-resource allocation mechanism for this environment, termed Task Share Fairness with External Resource (TSF-ER), and prove that it satisfies all desirable fairness and efficiency properties. We then consider the multi-AP MEC systems where no user can establish multiple wireless connections simultaneously to multiple edge servers. Furthermore, each user is a selfish agent that chooses the single server for its job execution that maximizes its utility. We propose the Multi-resource Allocation Game Induced by the Kalai-Smorodinsky bargaining solution (MAGIKS) and prove that under discrete resource demands, it finds a Nash Equilibrium in polynomial time for any fixed server configuration. Furthermore, we prove that MAGIKS satisfies some desirable fairness and efficiency properties. Finally, we consider the multi-AP MEC systems where each user can establish wireless connection simultaneously to multiple edge servers and may experience different levels of wireless channel quality on different APs, so the user's channel bandwidth demand is not fixed. We show that the four fairness and efficiency properties are no longer compatible in this MEC environment. Hence, we propose a resource allocation rule, Maximum Task Product (MTP), that retains PO, EF, and SI.
Next-Generation Postsynaptic Density-95 (PSD-95) Protein Inhibitors for the Treatment of Acute Ischemic Stroke
Keywords: AIS
Drug therapy
Excitotoxicity
Neuroprotection
PSD-95 Inhibition
Stroke

Stroke is the leading cause of neurological disability worldwide, creating a significant burden on health care systems. Although reperfusion therapies improve functional prognosis, this benefit is still time-dependent, and there is still a significant number of AIS patients with poor outcomes. Neuroprotection is an alternative strategy to reperfusion, aiming to enhance the brain's resilience to the ischemic cascade after stroke. Neuroprotection for experimental AIS has been demonstrated with nerinetide, an inhibitor of the protein-protein interactions of the synaptic scaffolding protein PSD-95. However, a potential adverse occurrence with the use of nerinetide is hypotension, produced by histamine release from mast cells. Therefore, we sought to develop a next-generation PSD-95 inhibitor intended to overcome the potential for hypotension currently seen with nerinetide. Three hypotheses were examined: (1) That the hypotension caused by nerinetide can be attenuated or eliminated while maintaining therapeutic effectiveness by co-formulating nerinetide with an agent that prevents mast cell degranulation, (2) That the hypotension caused by nerinetide can be attenuated or eliminated while maintaining therapeutic effectiveness by replacing the polycationic Tat N-terminus with an alternative CNS delivery domain and (3) That the hypotension caused by nerinetide can be attenuated or eliminated while maintaining therapeutic effectiveness by designing an alternative PSD-95 inhibitor altogether. These hypotheses were tested using three peptides (NA-1Lodo, Myr-NA1 and Myr-ND2) whose structural modifications from nerinetide corresponded to the three hypotheses. These were evaluated through a sequence of in-vitro and in-vivo studies evaluating their essential properties and culminating with PK/PD relationships. Of the three, NA-1Lodo demonstrated a plasma stability, pharmacokinetic profile and brain penetration like those of nerinetide. It also exhibited a superior safety profile to the other candidates, as it completely abolished the development of histamine induced hypotension following bolus administration. Additionally, NA-1Lodo demonstrated a significant neuroprotective effect, reduced infarct volume and improved neurological function in three different experimental stroke models in the rat. The overall work in my thesis shows that it is feasible to improve on the safety and tolerability of nerinetide without sacrificing efficacy using several approaches, and provides the data needed to rank these strategies for the purposes of further future development.
Antimicrobial Treatment Duration for Bloodstream Infections in Critically Ill Children
Keywords: bloodstream infection
critical care
duration of therapy
pediatric

BACKGROUNDBloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children, but the optimal antimicrobial treatment duration is understudied. Adequate treatment duration is important to prevent clinical failure and infection relapse but treating for too long increase patients’ risks for developing adverse drug events, superinfections, and selection for antimicrobial resistance. This thesis describes preparatory work completed to justify and inform the design of a randomized controlled trial to evaluate antibiotic treatment durations for critically ill children with BSIs. METHODS We conducted four studies as preparatory work for a future trial: 1. Clinician practice survey to determine self-reported recommendations for antimicrobial treatment duration; 2. Retrospective observational study to describe actual treatment durations received by critically ill children with BSIs; 3. Systematic review of non-inferiority pharmacotherapy trials to examine prevailing non-inferiority margins used for mortality outcomes; 4. Retrospective observational study using PELOD-2 as an outcome measure to compare progression of organ dysfunction between children who received early or delayed adequate antimicrobial therapy. RESULTS In our survey, 64% to 99% respondents recommended 10 days of therapy for BSIs, depending on underlying source of infection. In our observational study, the median treatment duration was 15 (IQR 11-25) days. Longer durations were associated with greater severity of illness and central nervous system infections. The median non-inferiority margin size for mortality in non-inferiority trials was a 9% (IQR 4.2%-10%) absolute risk difference or 1.5 (IQR 1.3-1.7) relative to baseline mortality risks. We did not find an association between 3-hour delays of adequate antimicrobial therapy and change in PELOD-2 scores (0.05, 95% CI -0.76 – 0.87, p=0.9) between days 1 and 5 from the index BSI. CONCLUSIONS We found self-reported and actual practice heterogeneity on BSI treatment durations, and clinical equipoise to support a trial of shorter versus longer antimicrobial treatment in critically ill children. Current non-inferiority margins for mortality outcomes in published trials are large and variable. The use of organ dysfunction as an outcome measure for BSI trials requires further study.
Transcriptomic Profiling of Ischemia-Reperfusion in Human Lung Transplantation
Keywords: cell death
inflammation
ischemia-reperfusion

Lung transplantation is the only lifesaving option for patients with end stage lung disease. The most prominent issue in transplantation is a shortage of donor lungs. Only 20% of donated organs are healthy enough to endure the stress of ischemia reperfusion (IR), an unavoidable consequence of transplantation. A deep understanding of cellular and molecular mechanisms for lung injury are needed to accelerate development of therapeutic strategies for lung repair. In this thesis we utilize a transcriptomics approach to catalogue potential mechanisms of injury directly from human lung clinical samples.In our first study we aimed to dissect potential mechanisms of IR injury through comparison of the response of human lungs to either transplantation or ex vivo lung perfusion (EVLP) using microarrays. We then aimed to further study IR at the single cell resolution and to this end, developed a hypothermic dissociation protocol. Using our developed protocol, we then conducted a longitudinal single cell RNA sequencing (scRNA-seq) study in human lungs before and after reperfusion to explore the response of donor cell populations to IR. From our bulk gene expressions study, we found that both transplantation and EVLP activated pathways involving inflammation and cell death, suggesting that these responses were induced independent of recipient factors. To conduct scRNA-seq, we developed the first hypothermic dissociation protocol for adult human lung which generated single cell suspension containing at least 18 unique cell types including neutrophils. From our longitudinal scRNA-seq study, we characterized the response of donor populations to IR and found that epithelial and endothelial cells induce major inflammatory responses early on in reperfusion. Using a single nucleotide variant-based deconvolution technique we were also able to deconvolve recipient cell populations and identify important differences compared to donor cells. These descriptive studies have identified potential mechanisms of injury at the tissue and single cell level directly from human clinical samples. Many of these potential mechanisms of injury intersect with existing data from animal and in vitro models. The human data generated from these studies will help to improve models of lung injury during IR and accelerate the discovery of therapeutic strategies for lung repair.
Adaptive Transit Signal Priority Algorithms for Optimizing Bus Reliability and Travel Time using Deep Reinforcement Learning
Keywords: coordinated traffic signal control
deep reinforcement learning
headway adherence
public transit control strategies
transit reliability
transit travel time

Transit Signal Priority (TSP), a broadly used traffic signal control strategy, is traditionally designed for reducing transit delays at signalized intersections. Conditional TSP is popular in field applications, and research studies have often designed such strategy based on criteria-oriented yes or no rules, which target simple objectives and do not guarantee optimality. Although recent objective-oriented TSP systems began to consider the optimization of more objectives, headway adherence is rarely included. TSPs that addressed transit reliability issues commonly focused on improving the schedule adherence and were only able to reduce schedule delays by expediting buses. Headway regularity which is a critical performance indicator for high-frequency services has not received much attention. Algorithms that expedite late buses only have limited capacity to resolve short headway gaps. Moreover, objective-oriented TSPs most frequently use mathematical programming methods, the main concern with which is the requirement of explicit formulation and representation of the system performance, which typically includes assumptions that simplify the dynamic traffic environment greatly. These assumptions, like deterministic traffic flow could ignore or oversimplify the stochastic characteristics of the system. This PhD thesis proposes dual-objective adaptive TSP algorithms optimized using Deep Reinforcement Learning (DRL). These TSPs use loop detectors, and they optimize transit delays and reliability (i.e., headway adherence) at an individual intersection or multiple intersections. The proposed algorithms are trained and tested in a stochastic microsimulation environment in Aimsun Next that models a transit line segment with reliability issues in the City of Toronto. The performance of developed TSPs is compared against carefully developed baseline scenarios, including background signal timing plans without TSP, current TSP algorithm used in the field in the City of Toronto, and more advanced TSP algorithms with a machine-learning based bus arrival prediction model or DRL agents. These TSP systems are evaluated on a series of aspects including bus headway adherence, percentage of extreme headways, travel time, passenger experience, effectiveness under different traffic demand levels, and impact on the cross-street traffic delays. The developed DRL-based TSPs provide noticeable improvement in headway adherence and travel time at the individual and multiple intersections levels.
Structural Limitations of Data Protection Legislation for the Learning Health System: Proposing a Lex Specialis for Longitudinal Biomedical Data Use
Keywords: Bioethics
Biomedical data commons
Data protection law
Data stewardship
Health policy
Personalised medicine

Data protection legislation imposes presumptive limitations on the capacity of institutions to collect, use, and disclose personal information to safeguard individual interests such as informational self-determination and privacy. This legislation has shown itself ill-suited to the regulation of emergent data-driven activities in the health sector, including public health surveillance, biomedical research, and personalised medicine. These difficulties are accentuated in transnational and intersectoral efforts, due to the heightened legal compliance challenges that arise from the simultaneous application of multiple laws. To alleviate these difficulties, a novel legal paradigm of data stewardship is proposed. A model of longitudinal information stewardship in reliance on appropriate organisational structures, expert oversight, and technical safeguards is proposed as an alternative to data protection law. Such a model should be enacted through special purpose health-sector legislation to align individual privacy and the pro-social use of health-related personal information in the public interest.
Molecular Mechanisms of Mechanically Regulated Aortic Valve Disease: A Focus on the Wnt Signaling Pathway
Keywords: Aortic valve stenosis
Calcific aortic valve disease
FoxO1
Mechanobiology
Wnt/b-catenin signaling pathway

Calcific aortic valve disease (CAVD) is characterized by the thickening and calcification of aortic valve leaflets. CAVD is a multifaceted disease caused by aberrant differentiation of valvular endothelial cells (VECs) and valvular interstitial cells (VICs) in response to changes in physiological mechanical environments. VECs can undergo endothelial-to-mesenchymal transition (EndMT) and contribute to the resident pool of fibroblast cells (VICs) within the aortic valve and upon stimulation, VICs can differentiate into myofibroblast- or osteoblast-like cells. The Wnt/β-catenin signaling pathway has been implicated in CAVD, VIC myofibrogenic, and osteogenic differentiation, however, its roles in mechanically-regulated EndMT and VIC osteogenic differentiation have not been investigated. The first part of this thesis examines the role of matrix stiffness and β-catenin in EndMT of VECs and found that TGF-β1 induced EndMT in a stiffness- and β-catenin-dependent manner. Notably, the initiation of EndMT (disruption of cell morphology and membrane VE-cadherin expression) was insensitive to matrix stiffness, but α-SMA fiber formation and nuclear translocation of β-catenin both increased on stiff substrate. Endostatin treatment revealed that β-catenin was necessary for TGF-β1-induced transformation of VECs to α-SMA positive myofibroblasts, and this association was confirmed by immunofluorescent staining of sclerotic aortic valves. The second part of the thesis analyzed the role of β-catenin, FoxO1, and cyclic stretch on VIC osteogenic differentiation. We demonstrated for the first time that FoxO1 expression is increased and co-localized with Runx2 in calcified region of diseased human aortic valve using immunostaining. In vitro experiments using siRNA knockdown and exogenous overexpression confirmed the causal effect of FoxO1 on the expression of osteogenic genes RUNX2, ENPP1, and SPP1 in VICs. Surprisingly, β-catenin knockdown had no effect on VIC osteogenic gene expression and thus was unlikely to be a co-factor of FoxO1 in regulating VIC osteogenic differentiation. Although short-term mechanical stretch had no effect on FoxO1, β-catenin, and osteogenic gene expression, long-term stretch promoted dystrophic calcific nodule formation. The findings in this thesis characterized the role of Wnt/β-catenin signaling pathway in mechanically-regulated EndMT and VIC osteogenic differentiation, identified FoxO1 as a novel mediator of VIC osteogenic differentiation, and provided insights into the molecular mechanisms behind CAVD pathogenesis and potential therapeutic targets.