VictorJuiz/thesis huggingface dataset:
Pre-velar /æ/-raising in Ontario and Colorado English: Production, Perception and Metalinguistic Awareness

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.

Keywords: BAG-raising
Metalinguistic Awareness
North American English
Production-Perception Link
Speech Perception
Speech Production
Advisor: Schertz, Jessamyn
Fair Multi-resource Allocation for 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.

Keywords: Fair Resource Allocation
Game Theory
Mechanism Design
Mobile Edge Computing
Advisor: Liang, Ben
Next-Generation Postsynaptic Density-95 (PSD-95) Protein Inhibitors for the Treatment of Acute Ischemic 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.

Keywords: AIS
Drug therapy
Excitotoxicity
Neuroprotection
PSD-95 Inhibition
Stroke
Advisor: Tymianski, Michael
Critical Illness in Patients with Hematologic Malignancies

Introduction: Patients with hematologic malignancy are at increased risk of developing life-threatening complications that can lead to admission to an Intensive Care Unit (ICU). Acute respiratory failure is the most frequent reason for ICU admission in these patients. Existing knowledge gaps in the field include the lack of population-based estimates of the incidence and timing of ICU admission in these patients and the associated risk factors; uncertainty about the relative effectiveness of treatments for acute hypoxemic respiratory failure; and information about long-term outcomes and symptoms for patients with hematologic malignancies who survive an ICU admission. Objectives: This thesis 1) characterizes the epidemiology of critical illness after a new diagnosis of hematologic malignancy in a large population-based cohort in Ontario, Canada; 2) evaluates the effectiveness of different noninvasive oxygenation strategies for reducing the receipt of invasive mechanical ventilation and decreasing mortality in patients with acute hypoxemic respiratory failure; and 3) describes the association between ICU admission and subsequent patient-reported symptoms in patients with hematologic malignancies who received hematopoietic cell transplantation. Synthesis: Between April 1st 2006 and March 31st 2017, 87965 patients were diagnosed with hematologic malignancy in Ontario. The one-year incidence of ICU admission was 13.9% (median time to ICU 35 days), ranging from 7.3% for patients with indolent lymphoma to 22.5% for patients with acute myeloid leukemia. Among ICU patients, 36.7% required invasive mechanical ventilation and in-hospital mortality was 31.0%. We found that the use of noninvasive ventilation provided by either a helmet or a face mask interface or use of high flow nasal oxygen decreased the risk of receiving invasive mechanical ventilation or dying in patients with acute hypoxemic respiratory failure. Among 5844 patients with hematologic malignancy who received hematopoietic cell transplantation, ICU admission was associated with a higher risk of reporting moderate to severe symptoms during follow-up across multiple symptom domains. Conclusion: This thesis provides important findings about the epidemiology of ICU admission for patients with a new hematological malignancy and describes the impact that ICU admission and treatments can have on subsequent outcomes.

Advisor: Scales, Damon C
“An Inborn Idea…to be Realised.” Imagining the Polish Nation within the Great Emigration in France, 1831-1846

In 1795, the Polish-Lithuanian Commonwealth ceased to exist with the third and final partition of the country by Prussia, Russia, and Austria. The nobility had held a wide array of rights and privileges that included the electoral sovereignty to choose the Polish king. The partitions thus resulted in a loss of agency for this class and provoked questioning as to whether their “fatherland” was gone indefinitely. Instead, deprived of a state, those who still identified with the fallen polity were inspired to conceive and construct the outlines of a nation without territory. The dissertation begins by examining Polish national philosophies post-partition, up to and including the November Uprising of 1830-31. Alongside themes of loss and suffering, writings centred on de-coupling the ideas of nation and state and envisioning the nation as a non-material entity. The nation began to be conceived through the idea of entelechy: in a process of self-realisation from an inborn idea, usually by means of a national mission. The focus of the dissertation is on the national thought of the members of the Great Emigration who mostly settled in France after the Uprising. Their writings on the nation built on currents that had emerged post-partition, and were heavily reliant on religious language, metaphor, and biblical inspirations. By focusing on a spiritual body reminiscent of a corpus mysticum, nationalists sought to prove and maintain continuity with the past, without the intermediary of a physical body politic. Émigrés were still concerned with the physical embodiment of a future Poland: debating boundaries, ethnic composition, religious minorities, and social questions. Contending with a deep sense of personal loss and with hopes for return diminishing, many émigrés turned toward mystical currents that viewed Poland through a messianic lens. They imagined an ideal nation that through its suffering and mission would serve as an agent of universal moral transformation. The dissertation closes with the failed Krakow Uprising of 1846 and the Galician Slaughter, which forced exiles to confront their imagined nation with the failure of the peasants, often idealised as the wellspring of national identity, to identify with and join the Polish cause.

Advisor: Wrobel, Piotr J
Antimicrobial Treatment Duration for Bloodstream Infections in Critically Ill Children

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.

Keywords: bloodstream infection
critical care
duration of therapy
pediatric
Advisor: Daneman, Nick
Transcriptomic Profiling of Ischemia-Reperfusion in Human Lung Transplantation

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.

Keywords: cell death
inflammation
ischemia-reperfusion
Advisor: Liu, Mingyao
Adaptive Transit Signal Priority Algorithms for Optimizing Bus Reliability and Travel Time using Deep Reinforcement Learning

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.

Keywords: coordinated traffic signal control
deep reinforcement learning
headway adherence
public transit control strategies
transit reliability
transit travel time
Advisor: Shalaby, Amer AS
Structural Limitations of Data Protection Legislation for the Learning Health System: Proposing a Lex Specialis for Longitudinal Biomedical Data Use

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.

Keywords: Bioethics
Biomedical data commons
Data protection law
Data stewardship
Health policy
Personalised medicine
Advisor: Austin, Lisa
The Empathy Selection Task: Evaluating Empathy as a Subjective Value-based Choice

Empathy often feels automatic, but variations in empathic responding suggest that, at least some of the time, empathy is affected by one’s motivation to empathize in any particular circumstance. Here, I investigate a novel free-choice behavior measure of motivated empathy avoidance called the empathy selection task. First, I assess the suitability of the empathy selection task for use in individual difference and experimental research by examining its reliability within and across testing sessions, and by examining rank order stability of summary scores (Studies 1a and 1b). The empathy selection task is stable between testing sessions and has good/substantial test-retest reliability (ICCs = .65 and .67), suggesting that it is comparable or superior to other commonly used experimental tasks with respect to its ability to consistently rank individuals. Next, I show that people can be motivated to engage in (or avoid) empathy-eliciting situations with strangers, and that these decisions are driven by subjective value-based estimations of the costs (e.g., cognitive effort) and benefits (e.g., social reward) inherent to empathizing. Participants were more likely to opt into empathy-eliciting situations if 1) they were incentivized monetarily for doing so (Studies 2a and 2b), and 2) if a more familiar and liked empathy target was available (Studies 3a and 3b). Framing empathy as explicitly related to one’s moral character and reputation did not motivate participants to engage in empathy (Studies 4a and 4b), though these null results may be due to a weak manipulation. These findings suggest that empathy can be motivated in multiple ways, and that context-specific value-based decision can be captured and measured by the empathy selection task.

Advisor: Inzlicht, Michael
Segal, Zindel