title: The Effects of TET2-Deficiency on Neutrophil Gene Expression and Function

contributor:
Rauh, Michael
Pathology and Molecular Medicine

subject: CHIP Neutrophil Hematopoiesis Genetics TET2 Epigenetics

abstract:
Background: Clonal hematopoiesis of indeterminate potential (CHIP), a potential precursor to myelodysplastic syndrome (MDS), affects over 10% of adults over 65. Loss-of-function ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) variants are common in CHIP and associate with epigenetic dysregulation, inflammation, and cardiovascular disease. Although neutrophils are sensitive to epigenetic dysregulation and contribute to many cardiovascular diseases, the effects of TET2-deficiency on neutrophils have not been characterized. We hypothesize that TET2-deficiency dysregulates gene expression and function in neutrophils.

Methods: With informed consent and ethics approval, serum and peripheral blood (PB) were collected from CHIP subjects and controls. RNA was extracted from whole PB and mRNA expression of two representative neutrophil granule genes, myeloperoxidase (MPO) and lactotransferrin (LTF), were assessed using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). MPO and LTF serum protein titers were quantified with enzyme-linked immunosorbent assays (ELISA). Additionally, the Tet2flox/flox Vav-iCre mouse model was used to investigate the effects of Tet2-deficiency on neutrophils. Motility and phagocytosis were assessed through a Staphylococcus aureus phagocytosis assay. RNA sequencing (RNA-seq) was performed to analyze transcriptomic differences in Tet2-deficient neutrophils at baseline and after stimulation with S. aureus-derived lipoteichoic acid (LTA). DESeq2 and g:Profiler were used for differential expression analysis and functional annotation, respectively.

Results: CHIP subjects had increased serum protein titers of MPO (p=0.006) and LTF (p=0.001) compared to controls, but MPO and LTF mRNA expression did not differ significantly. Tet2-deficient murine neutrophils exhibited impaired phagocytosis (p=0.034) and motility (p=0.004). Genes related to motility, the interferon response, and neutrophil development were dysregulated in Tet2-deficient murine neutrophils. Overall, the results suggest that Tet2-deficiency affects neutrophil gene expression and function.

Discussion: This study addresses a gap in the literature by investigating the effects of TET2-deficiency on neutrophils. Since high MPO titers associate with cardiovascular disease, elevated MPO serum protein titers in CHIP subjects may exacerbate comorbidities. While Mpo was not overexpressed in Tet2-deficient murine neutrophils, they exhibited features associated with MDS, such as overexpression of interferon response genes and impaired neutrophil function. We suspect that dysfunctional Tet2-deficient neutrophils may also contribute to increased susceptibility to infection, and call for confirmation through human population studies.

abstract: M.Sc.


title: Identification of Novel Small Molecule Inhibitors (SMI) of YAP/TAZ Oncoproteins in Breast Cancer Using HiBiT Bioluminescent Biosensors

contributor:
Yang, Xiaolong
Pathology and Molecular Medicine

rights: Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada

rights: ProQuest PhD and Master's Theses International Dissemination Agreement

rights: Intellectual Property Guidelines at Queen's University

rights: This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.

subject:
YAP
TAZ
Breast Cancer
Biosensor
Bioluminescence

abstract:
Breast cancer (BC) is the most frequently diagnosed cancer among females, accounting for 25% of all cancer cases worldwide. Among all the subtypes of BC, triple negative breast cancer (TNBC) is considered one of the most-deadly killers in the world, characterized by its increasing incidence and poor prognosis, which demands improved targeted therapy urgently. Recently the Hippo signaling pathway has emerged as an important cellular network mediating tumorigenesis, drug resistance and cancer metastasis. Current evidence indicates that the core Hippo components YAP and its paralog TAZ are involved in the tumorigenesis and metastasis of TNBC. Therefore, targeting YAP/TAZ may be a promising strategy for TNBC therapy. However, few YAP/TAZ-targeted drugs have been identified and no YAP/TAZ-targeted drug has been used for clinical cancer treatment.
In my thesis project, I hypothesize that the Hippo pathway, especially the Hippo output mediators YAP/TAZ can play a central role in the development, metastasis, drug resistance of TNBC; and are therefore potential “druggable” targets for TNBC therapy. To test this hypothesis, the following specific objectives will be carried out:
1. Establishment of HiBiT-tagged YAP/TAZ bioluminescent biosensors in monitoring YAP/TAZ levels in cells
2. Screen for small molecules regulating the stability of YAP/TAZ in TNBC cells
3. Characterization of small molecules targeting YAP/TAZ in TNBC cells

abstract: M.Sc.


title: Carbon Nanotube Polymer Composite Based Electrodes with Ability to Adhere to Hairy Skin for Application in Electrophysiological Sensing

contributor:
Kabiri Ameri, Shideh
Electrical and Computer Engineering

subject:
Sensors
Electrophysiology
Carbon Nanotubes
Wearable Devices

abstract:
Biopotential recordings such as electroencephalogram (EEG) and electrocardiogram (ECG) measurements have applications in medical diagnosis, health care, human-machine interface, entertainment, etc. Electrodes are an important part of biopotential acquisition systems affecting the quality of recorded signals, comfort to the user, and the cost. Many conventional electrodes are either expensive or disposable, many are rigid and non-conformal to the skin, and some cause irritation and allergic reaction due to the use of aggressive chemical adhesives. Further, Silver/Silver Chloride (Ag/AgCl) electrodes are the only medical grade electrodes available for EEG measurements from the scalp. They are placed using EEG hats and a conductive gel is filled between the electrode and the scalp. Sometimes this gel leaks out causing shorting between consecutive electrodes. Such systems consume time to place on the head, requires assistance from experts, and restricts the user movements. Non-medical grade dry electrodes are used as an alternative to Ag/AgCl electrode setups for EEG measurements, but they require mechanical support to attach, and therefore, they are susceptible to motion artifacts. Hence, there is a need for a soft wearable electrode that is cost-effective, reusable, and can adhere to the skin regardless of the level of hair coverage and topology of the skin.
This thesis presents a novel soft reusable carbon-nanotube-polymer composite based electrode capable of biopotential recording from a high dense hairy area such as the scalp. The electrode consists of an array of tulip-like microstructures that utilizes suction force in combination with the use of trace amount of medical-grade conductive gel to achieve sufficient adhesion force and conformability to hairy skin for biopotential recording. A novel low-cost scalable fabrication process was developed, and mathematical and experimental analysis of capillary rise that plays a key role in the optimization of the fabrication process was carried out. The proposed electrode was fabricated and electrophysiological signal measurements were performed. The electrode can adhere to the skin conformably resulting in low electrode-skin interface impedance and good signal to noise ratio. The electrode is found to be very comfortable to the users and capable of recording ECG and EEG for an extended amount of time.

abstract: M.Sc.


title: Structural Design of a Morphing Serpentine Inlet Using a Multi-Material Topology Optimization Methodology

contributor:
Kim, Il Yong
Mechanical and Materials Engineering

subject: Optimization Morphing Multi-Material

abstract: A promising avenue for development in the aerospace industry involves relocation of engines from conventional locations beneath the wings, to within the aircraft fuselage. Aircraft with these so-called embedded engines have the potential to increase engine efficiency, but necessitate the use of a serpentine engine inlet duct (S-duct) to provide the propulsion system with air. The optimal shape of an aircraft S-duct varies with flight condition, incentivizing the use of morphing systems to vary inlet parameters during flight; allowing for continual supply of the optimal airflow level. Design of a morphing system therefore requires collaboration across multiple disciplines, including aerodynamic analysis and structural analysis. This work presents a methodology for the structural optimization of morphing systems utilizing aerodynamic shape optimization results as inputs, in order to assess the relationship between morphing performance and structural stiffness. The methodology is implemented on a baseline morphing S-duct model for which shape optimization has been previously conducted. Structural optimization is conducted using a gradient-based multi-material topology optimization software with multi-phase penalization. While the conclusions of this work indicate that the impact of multiple material optimization in the S-duct case study is minimal, the methodology does provide non-intuitive designs capable of supporting morphing. At the expense of structural stiffness, the methodology is shown to increase morphing performance through the generation of compliant mechanisms. A parameter study conducted on the S-duct model successfully proves the ability of the methodology to assess the trade-offs between structural and morphing performance. By emphasizing morphing performance, mass reductions from 1.75 kg to 0.201 kg were observed at the expense of a 94% reduction in fatigue lifecycle. In addition, through verification with commercial software, the generalizability of the optimization software developed in this work is proven.

abstract: M.A.Sc.


title: Control of the Adsorption of Rare Earth Elements on Gypsum (in Hydrometallurgical Processes)

contributor:
Ghahreman, Ahmad
Mining Engineering

subject:
Rare Earth Elements
REE
Gypsum
Calcium Sulfate Dihydrate
Calcium Hydroxide Neutralization
Impurity Removal
Hydrometallurgy
Processing

abstract: The purity of the final rare earth elements (REE) product is a valuable key factor for the market. Therefore, elimination of impurities is a prominent step in REE producing route which is performed after water leaching of the acid baked REE concentrate. Lime neutralization is a preferred process due to its high efficiency in the removal of impurities and low reagent cost. However, drawbacks such as co-precipitation of REE with calcium sulfate dihydrate (CaSO4·2H2O, CSD), which results in a significant REE loss, renders this process inefficient. This study focuses on reducing in the operating costs and improving the process by lowering the REE loss during the impurity removal step from the pregnant leach solutions (PLS). The elimination of REE can have substantial impact on the feasibility of the process. A feasible route to eliminate or minimize the REE loss associated with the lime neutralization process is to use a crystal habit modifier to alter the crystalline morphology and surface properties of CSD and subsequently reduce the portion of REE lost to the CSD. In this study, cetryltrimethylammonium bromide (CTAB) and polyacrylic acid (PAA) were employed as cationic and anionic modifiers at concentrations of 0.2, 2, and 5 g/L to reduce the REE loss to CSD in a titration process simulating the impurity removal step. In addition, the effects of temperature and Ca(OH)2 pulp density on the co-precipitation process and morphology changes were investigated. The mechanism of co-crystallization and sorptive properties of rare earth elements (REE) with calcium sulfate dihydrate (CSD) crystallization were examined thoroughly using an array of characterization techniques such as SEM, XPS, ToF-SIMS and so on. The effects of the two of the main impurities, Fe and Al, and different reagents of Ca(OH)2, Mg(OH)2, and NaOH were investigated to remove Fe and Al from the synthetic REE leaching solution. Four different concentrations of 4, 2, 1 and 0.5 g/L for Fe and Al impurities were examined. Also the REE loss at different impurity contents was studied using Ca(OH)2 for neutralization. Finally, based on the results of the study a two-step impurity removal process was proposed to remove iron and aluminum. This process was followed by acid leaching of the gypsum-Al-Fe residues of each step to recover the lost REE from the residue and thus improve the efficiency of the process with Ca(OH)2.

abstract: PhD


title: DeepSkin: Mobile-based Skin Quality Assessment with Deep Learning

contributor:
Etemad, Ali
Woo, Kevin
Electrical and Computer Engineering

subject:
Skin Quality
Dermoscopy
Deep Learning
Machine Learning
Frailty
Dry
Hair

abstract: We present a novel skin quality assessment system with the goal of improving skin care. This system leverages digital dermoscopy and consists of hardware, software, and a machine learning component to automate the process of skin quality assessment. We first give a brief introduction to the problem followed by and in-depth overview of skin assessment and related works. Following this, the different components of the system are described along with the data collection and algorithms. We performed two studies with 114 participants in total. These studies yielded 2332 skin images that were ranked by experts across a number of skin quality metrics. We plan to release this dataset as part of this work. Using this data we trained several classical and deep learning algorithms to classify Dryness, Frailty, and existence of hair for the images. The best performance for Dryness detection was achieved by VGG16 with an accuracy of 0.8606, while Frailty was best classified by VGG19 with an accuracy of 0.7929. Additionally, Hair was best detected by VGG16 with an accuracy of 0.8756 We believe our proposed and developed system creates a new research direction in the area of digital mobile-based dermoscopy, showing the feasibility of low-cost, mobile, and reliable skin quality assessment.

abstract: M.A.Sc.


title: Bracketing Off, Dashing Away: Unruly Punctuation in A.A. Milne’s A Table Near the Band

contributor:
Varadharajan, Asha
English Language and Literature

subject:
Literature
Punctuation
Parentheses
Dashes
Parenthetical
Milne
Short Story
Children's Literature

abstract: I argue that Milne uses the diacritical marks of parentheses and dashes, and the asides they denote, to destabilize the written page in his short-story collection A Table Near the Band. Parentheticals produce this destabilization two-fold: syntactically through the creation of separate, grammatically unfettered spaces; and logistically through both the historical proscription of parenthetical punctuation, and the fact that the text these marks enclose is often thought of as syntactically and narratively inferior. In this sense, Milne’s use of parentheses and dashes in A Table subtly echoes his alternate spelling, capitalization, and punctuation use in his children’s literature. Like these grammar transgressions, parentheticals draw attention to text as text, exposing writing as something that is constructed and, thus, not infallible or absolute. My argument functions primarily on Theodor W. Adorno’s idea that “bracketed parentheses, which interrupt both the graphic image and the narrative, are memorials to the moments when the author, weary of aesthetic illusion and distrustful of the self-contained quality of events which he is after all only making up, openly takes the reins” (304). While Adorno’s explanation focuses only on brackets, I extend the sentiment to dashes as well. Precisely because they are thought of as disruptive or unnecessary, the parenthetical marks that appear in A Table become more consequential: the marks become material signs and figures of written form, crucial to Milne’s characteristic style and indicative of authorial deliberation. By examining these pieces of punctuation, my analysis not only illuminates the complicated semiotic status of parentheticals, but explores their tethering of language and imperceptibility as a way to navigate the tensions implicit in Milne’s writing: between orality and writtenness, between literary time and space, and between necessity and superfluity.

abstract: M.A.


title: A Study of Energy Democracy in Mexico

contributor:
McDonald, David
Environmental Studies

subject:
Energy Democracy
Mexico
Renewables
Energy Transition or Transformation

abstract:
Endorsing ‘energy democracy’ is an attempt to attain sustainable electricity. Although this ultimate goal is somewhat clear, conflict characterizes the different roads leading to the ‘ideal’ provision of this essential service. Public and private alternatives differ, and pro- and anti-market convictions. Despite being a polarized field, energy democracy is very rich because of its multidisciplinarity. It gathers issues concerning environmental and development studies, economics, philosophy, sociology, political science, engineering, and more.
This particular study of energy democracy is twofold. First, I tackle the topic from a general, international perspective. Second, I focus on the specific case of Mexico. For both instances, I conduct a literature review of primary and secondary sources. I find that there is a lack of consensus on a definition of energy democracy, impelled by the wide ideological spectrum and lax theoretical boundaries. Thus, I claim five fundamental principles can better explain the term which I obtained from searching the most shared items in the range of advocacy. These principles are Decarbonization, Decentralization, Digitalization, Democratization and Equity (DDDDE). Also, my investigation intends to achieve more clarity by proposing an original categorization of energy democracy. I state there are three main typologies on the ground: neoliberal, statist and communitarian.
After discussing the key lines of debate among typologies, I present a fieldwork component where I assessed the development of energy democracy in Mexico. By analyzing explicit and implicit mentions, and interviewing senior managers from private renewable energy companies (start-ups and B-corps), I conclude several approaches have been present in such context since the late 2000s, especially those qualifying as neoliberal. Such findings are relevant because most studies on energy democracy centre on European countries or the United States. In addition, most advocates sustain that energy democracy is strictly reserved for public ownership and finance. In contrast, my argument is that there are multiple forms of energy democracy, including private-oriented approaches. This research could be useful for individuals and organizations who wish to learn more about the different conceptions of the term, and also about a Latin American country which is debating about renewables and the democratization of energy.

abstract: M.E.S.


title: Quantifying Rooftop Solar Photovoltaic Potential with Socio-Economic Factors: A Case Study for Kingston, Canada

contributor:
Mabee, Warren
Geography and Planning

subject:
Renewable Energy
Microgeneration
Geographic Information Systems
Rooftop Solar pv
Socio-Economics

abstract: This half thesis describes a proposed research project to explore how geographic information systems (GIS) can be used to find possible correlations between the physical requirements for rooftop solar photovoltaic (RSPV) technology and socio-economic data, to enhance a city-wide strategy for renewable energy implementation. The advantage of RSPV is the ability to be decentralized and distributed on existing infrastructure within the built environment, especially in circumstances where landuse policies may prohibit additional land development. While the cost of RSPV has been decreasing over the past two decades, there are still logistical, financial, and social challenges to city-wide implementation. Recent studies have found that both the physical requirements for RSPV and the socio-economic potential of a city are strongly influenced by the nature of the local building stock. Therefore, this proposed research will take a case study approach for Kingston, Canada to determine the potential for RSPV implementation and explore the constraints that socio-economic indicators such as income or acceptance behaviour might have on deployment within this context.  The purpose of this study is to understand potential correlations between physical feasibility and socio-economic factors to: 1) determine which type of GIS methods accurately quantify RSPV potential for Kingston depending on the quality of data available; 2) apply the most appropriate GIS methods from the results of objective one to the municipal region of Kingston, to determine the amount, location, and distribution of rooftops that are physically and geographically feasible for RSPV deployment; and 3) determine and highlight the locations within the study area where socio-economic data is favourable for RSPV deployment, and where these areas overlap with physical feasibility for RSPV deployment. Delivery of this proposed research project would further explore the use of GIS in understanding the connection of renewable energy implementation to the people living in the community, alongside the physical, geographic, technical, economic, and environmental feasibility. This type of comprehensive analysis can create a more complete picture for informed decision-making.

abstract: M.Sc.


title: DISCOVERY AND INVESTIGATION OF THE BIOSYNTHESIS OF A NOVEL LANTHIPEPTIDE MOLECULE FROM A MARINE BACTERIUM Pseudoalteromonas flavipulchra 2ta6

contributor:
Ross, Avena
Chemistry

subject:
Biosynthesis
Marine Bacteria
Pseudoalteromonas
Lanthipeptide
Flavipuricin

abstract:
Bacterial natural products have been a rich source of therapeutics since ancient times. Genome sequencing has shown the potential of bacteria to produce even more Natural Product molecules. Lanthipeptides are ribosomally synthesized and post-translationally modified peptide (RiPP) molecules characterized by the presence of thioether crosslinks known as lanthionines. Lanthipeptides are classified into four classes based on the biosynthetic enzymes involved to install the thioether crosslinks. In class I lanthipeptides, two distinct enzymes, a dehydratase and a cyclase are employed for this purpose whereas in other classes the thioether crosslinks are formed by a bifunctional enzyme. Development of genome mining tools have made it possible to find lanthipeptide encoding gene clusters from the bacteria of multiple different phyla. Lanthipeptide structures can be predicted based on gene sequence information and the types of post-translational modification enzymes present, enabling the isolation and chemical structure elucidation of these RiPPs allowing subsequent bioactivity testing and investigation of the biosynthesis.
 This thesis describes the isolation the new lanthipeptide molecule flavipuricin I (18) from a gram-negative marine proteobacteria Pseudoalteromonas flavipulchra 2ta6 and the attempts taken for in vitro and in vivo production using Escherichia coli as a heterologous host. A genome mining approach combined with mass spectrometry guided isolation and structure elucidation was adopted for discovering flavipuricin I (18). Also, the co-expression of genes for synthetases from flavipuricin I (18) biosynthetic pathway, yielded post-translationally modified flavipuricin I (18). The biosynthetic enzymes were successfully purified for a future in vitro biosynthesis of flavipuricin I (18) .  Further, the identification of a peptidase containing transporter (FlnT) suggests a new role for bifunctional transporters in class I lanthipeptide biosynthesis. To the best of our knowledge flavipuricin I (18) is the first lanthipeptide isolated from a proteobacterium, suggesting this phylum may be a promising future source of new lanthipeptides

abstract: PhD


title: “Adultery” in Canadian Family Law: A Zombie Category?

contributor:
Baines, Beverley
Baines, Beverley
Law

subject:
Adultery
Constitutional Law
Vagueness Doctrine
Divorce
Family Law
Legal History
Zombie Category
Zombie Law

abstract:
The focus of this thesis is upon the construction of “adultery” within Canadian divorce law. I argue that this legal construct is exemplary of what social theorist Ulrich Beck described as a “zombie category” - a moribund concept that haunts the living. It is my contention that this construct is unconstitutionally vague and should be jettisoned.

I locate the origins of this matrimonial fault and chart its development over time. I emphasize that until recently, the definition of adultery that informed Canadian family law was robustly heterosexist, phallocentric and anchored in an understanding of procreation as the sine qua non of marriage. Adultery, as defined in Kahl v Kahl (1943), [1943] OJ No 365 referred to "voluntary sexual intercourse by a married person with another person of the opposite sex other than his or her spouse.” In a post-Charter era, P(SE) v P(DD), 2005 BCSC 439 and Thebeau v Thebeau, 2006 NBBR 154 made clear that the definition of adultery must be consistent with the governing legislation and the values that the Charter enshrines. However, neither case furnished a definition of adultery that serves this purpose and, as of 2020, this void remains unfilled. I forward two models of how adultery might be operationalized in judicial determinations of the occurrence of this matrimonial fault and describe the problems that inhere in each.

abstract: LL.M.


title: Studying Dependency Maintenance Practices Through the Mining of Data from npm Packages

contributor:
Hassan, Ahmed
Computing

subject:
Software Ecosystem
Dependencies
Package Manager
Dependency Management
Downgrades
Releases
Deprecation

abstract: Open source software ecosystems have gained significant importance in the last decade. In a software ecosystem, client packages can enable a dependency to reuse the functionalities of a provider package. On the one hand, the diversity of freely reusable provider packages in those ecosystems supports a fast-paced contemporary software development. On the other hand, developers need to cope with the overhead brought by dependency maintenance. Dependencies need to be kept in an updated and working state, otherwise defects from provider packages can negatively impact client packages. Notable incidents denote the importance of timely and proper dependency maintenance. For example, in the "Equifax data breach", a vulnerability coming from an out-of-date dependency was explored to illegally obtain hundreds of millions of financial customers information Also, the "left-pad incident", in which a package with 11-lines of code was removed from \npm, caused a significant downtime on major websites such as Facebook, Instagram and LinkedIn. Hence, proper dependency maintenance contributes to the viability of both individual packages and the whole ecosystem. In this thesis, we propose to leverage data from the npm ecosystem to understand the current dependency maintenance practices and provide actionable information to practitioners. Currently, npm is the largest and most popular open-source software ecosystem. We study three phenomena related to the dependency maintenance in software ecosystems: downgrade of dependencies, same-day releases, and releases deprecation. In this thesis, we discuss in detail the motivation and approach to study these three phenomena. We then perform an empirical analysis of the npm data to evaluate the driving forces behind these phenomena, as well as their prevalence and impact in the ecosystem. Based on our empirical observations, we propose a set of informed suggestions to improve dependency maintenance practices in npm.

abstract: PhD


title: Towards Reliability Evaluation and Integration in Cloud Resource Management

contributor:
Zulkernine, Mohammad
Computing

subject:
Cloud Reliability
Reliability Evaluation
Virtual Machine Allocation
Virtual Machine Migration
Cloud Federation Formation

abstract:
The adoption of cloud computing technology is increasing day by day due to its enormous services and low cost. Customers transfer their businesses to cloud because of the beneficial cloud features such as scalability, high performance, on-demand, and pay-per-use service model. However, transferring services to cloud adds a new level of risk due to loss of control, which makes service reliability an essential driving factor of the cloud market today, especially in light of the recent cloud failures and outages that raise customers' concerns.
In this thesis, the goal is to propose a reliability evaluation model and integrate the developed model in cloud resource management such as Virtual Machine (VM) allocation, VM migration, and cloud federation formation in order to increase the cloud service reliability. In this thesis, firstly a cloud reliability evaluation model is proposed. Some types of failures from different domains of the cloud environment are considered to evaluate cloud reliability. To propose the evaluation model, a classification strategy for cloud failures is also outlined. Secondly, to show the impact of the integration of the proposed model, a multi-objective placement model for interdependent VMs in cloud is proposed while considering both reliability and some quality of service. A multi-objective genetic algorithm is used to solve the placement problem heuristically. Thirdly, a Markov-based failure prediction model is proposed to anticipate the failures of cloud servers. The proposed prediction model is then integrated into a VM migration model in a multi-cloud setting to maximize cloud reliability while reducing VM communication delay. The VM migration problem is solved optimally and heuristically using the Artificial Bee Colony (ABC) algorithm. Finally, a reliability-based cloud federation model is proposed using a hedonic coalition formation game based on a reliability-driven utility function. All proposed models will serve as a guide to both customers and cloud service providers towards the achievement of reliable resource allocation, migration, and federation formation. The effectiveness of all the models has been demonstrated through experiments. The evaluation shows that the models are computationally efficient and achieve higher cloud reliability.

abstract: PhD


title: Cognitive Training in Major Depressive Disorder: Perceptions of Cognitive Malleability, Importance of Autonomy, and Efficacy of a Brief Psychoeducational Intervention

contributor:
Bowie, Christopher
Psychology

subject:
Major Depressive Disorder
Cognitive Remediation
Cognitive Training
Engagement
Psychoeducation
Home Practice
Motivation

abstract: Cognitive difficulties constitute a diagnostic criterion of major depressive disorder (MDD) and are associated with functional impairments and barriers to recovery in this condition. Cognitive Remediation (CR) is a psychotherapeutic treatment that aims to improve cognitive and functional skills; however, engagement in CR is varied, contributing to a range of outcomes. Though this treatment has demonstrated efficacy in MDD, a major gap in the literature pertains to factors that may underlie approach of cognitively challenging activities, and methods of fostering willingness of this population to engage in CR. In this dissertation, Chapter 2 presents correlational relations of objective cognition, perceived malleability of cognition, and approach of cognitive activities; and factors associated with reported willingness to engage in CR for participants with MDD. Though perceived cognitive malleability did not moderate the relationship between objective cognition and approach of cognitive challenges, it was significantly positively associated with willingness to engage in CR, alongside subjective approach of daily cognitive challenges. Chapter 3 investigated whether participants endorse greater engagement, perceived competence, and motivation to participate in cognitive exercises as a function of whether they self-select their difficulty levels while training or if their training is algorithmically titrated by the program. Contrary to hypotheses, no significant difference was found in reported engagement or intrinsic motivation to participate in training; however, perceived competence ratings increased in the autonomous condition. Chapter 4 reports upon a psychoeducational video that was developed to educate participants about CR. Effects of this video on subjective and objective engagement in CR was studied. The intervention did not significantly increase MDD participants’ willingness to engage in CR, nor the degree to which they trained on computerized cognitive exercises during a 2-week period of at-home access, though a small effect on subjective cognition was found. This research provides initial steps in addressing a critical gap in the literature pertaining to bolstering engagement of participants with MDD in CR, with important implications for factors that may underlie engagement in CR at the outset of treatment. This work highlights the need for continued investigation into ways of inciting engagement in cognitive training for those with MDD.

abstract: PhD


title: Nurturing the Seed: A Collaborative Journey to Infant Mental Health and Wellness: Phase One

contributor:
Reynolds, James N
Neuroscience Studies

subject:
Child Development
Social Emotional Development
Community Based Participatory Research
Infant Mental Health
Knowledge Mobilization
Implementation Science

abstract:
Despite the known value of culturally meaningful practice in supporting mental health in Indigenous communities, there lacks culturally informed developmental assessment tools and interventions. Nurturing the Seed was designed to address this gap by providing tools to frontline practitioners who support the developmental needs of Indigenous children. These children are at greater risk for poor outcomes in part due to intergenerational familial trauma. Developed by Infant Mental Health Promotion with key stakeholders, NTS melds worldviews and practices of Indigenous communities with evidence-based assessment tools and customized developmental support planning utilizing a relational approach.
This thesis project was the initial part of a longitudinal, multi-part study to evaluate implementation of NTS in community. This project aimed to: (1) establish a research project to evaluate NTS in self-identified communities with methodology acceptable to both community members and the research team; and (2) train community service providers to adopt a culturally informed approach to supporting Indigenous children and families and in the skills and knowledge they need to implement a research project.
In six Canadian Indigenous communities, champions and leadership created a Community Steering Committee which included indigenous community representatives, childcare practitioners and Elders who provided cultural consultation on program design, methodology, and implementation. This was followed by a 3-day training led by IMHP to equip practitioners with infant mental health knowledge, ability to administer the developmental screening tool, and individualized developmental support plans using NTS. A pre/post training knowledge survey was used to evaluate training knowledge transfer.
Overall, there was positive uptake of the research program in all communities. Worker scores on training surveys increased from pre to post-survey, suggesting a positive knowledge transfer to the workers from the training. Attitudes and beliefs that were also examined in pre/post-surveys did not show a significant change on average, suggesting that staff had some prior motivation and were open minded to training material.
Results of this study demonstrate the feasibility of establishing a multi-site, community-based participatory research program aimed at improving long-term child outcomes. Future analyses will examine developmental outcomes in children who receive the intervention and practice change among community service providers.

abstract: M.Sc.


title: Firn Pack Changes on White Glacier, Axel Heiberg Island, Nunavut

contributor:
Thomson, Laura
Copland, Luke
Geography and Planning

subject: Arctic Glacier Firn

abstract: The near-surface processes and variability within the firn pack of Arctic glaciers are a significant source of uncertainty in estimating future glacier responses to climate warming. This study provides the first characterization of the firn pack of White Glacier, Axel Heiberg Island, Nunavut, and an analysis of recent firn pack changes (2013-2019). Utilizing ground penetrating radar (GPR) surveys the firn pack thickness, extent, and associated topographic controls on firn distribution were determined. Two methods of GPR analysis were tested in this study. The first followed the traditional approach of conducting visual interpretation of radargrams to identify zones of backscatter associated with firn. The second is a proposed new methodology that uses average backscatter values from each radar return as a proxy indicator of firn presence in the subsurface. The results of these two approaches showed that the firn pack on White Glacier has reduced in extent, and reductions in average backscatter values suggest that the density of the firn has increased in the near surface. Overall, the long-term firn area decreased in extent by 3.96 km2 (10% of the total glacier area) between 2013 and 2018. Rates of surface lowering were determined using dual-frequency GPS surveys. For spring 2018 to spring 2019 the rate was -0.165 ± 0.29 m a-1 in the accumulation area, likely driven by the near surface densification. The potential for average backscatter values to provide information about near surface snow water equivalence is also explored.

abstract: M.Sc.


title: Applications of Photogenerated “Dark Isomer” Boriranes: Dearomatization and Thermal Energy Storage

contributor:
Stamplecoskie, Kevin
Wang, Suning
Chemistry

rights: Attribution-NonCommercial 3.0 United States

subject:
Borirane
Photoswitch
Organoboron
Energy Storage
Dearomatization
Photochemistry

abstract:
The works described herein investigate the bimolecular ground state reactivity of boron-containing photochromic systems. Despite a remarkable development in the synthesis and characterization of N,C- and C,C-chelate organoboron species over the last decade, only their photoreactivity and photophysical properties have been well documented. Their ground state reactivity is largely unknown, and apart from luminescence, no applications exploiting their photochromic properties have been reported. To complement their photoreactive profiles, N,C- and C,C-chelate organoboron species will be reacted with conventional organic reagents to target specifically the boron center and boron-chelated ligands to elucidate structural changes in thermal conditions.

The first study describes the one-pot, light-assisted dearomative functionalization of N,C and C,C-chelate four-coordinate boron compounds via  [4+2] cycloaddition (Diels-Alder reaction) at a boron-anchored mesityl ring. The synthesis progressed rapidly under ambient conditions and all of the four products reported in this work contain a borirane ring that is stable towards oxygen, unlike its starting precursors which undergo oxidative deborylation. The simplicity of this post synthetic modification strategy prompts further investigation into boron-assisted dearomatization of simple aromatic rings.

The second study uses a N,C-chelate four coordinate boron photoswitch for solar energy storage. The compound of interest photoisomerizes from a four-coordinate organoboron to a borirane-containing species with 365 nm light and was found to liberate 14 kcal/mol of energy upon its thermally triggered reversion back to the original organoboron in the solid state. We find that the reverse reaction from borirane to N,C-chelate boron compound can be catalyzed by three salts containing the −B(C6F5) counter ion. Radical species were discovered as key intermediates in the reversal process and were detected via NMR and EPR spectroscopy. The facile reversal of the photoswitch and detection of heat generated in the reversal process make this class of compounds suitable candidates for solar energy storage applications.

abstract: M.Sc.


title: Neurophysiology of Exertional Dyspnea in Interstitial Lung Disease and Pulmonary Vascular Disease: Final Common Pathways

contributor:
O'Donnell, Denis
Biomedical and Molecular Sciences

subject:
Exercise Physiology
Interstitial Lung Disease
Pulmonary Embolism
Dyspnea

abstract:
Dyspnea is an important symptom that negatively impacts quality of life and results in functional limitation and disability. The overarching objective of this thesis was to explore mechanisms of chronic activity-related dyspnea in diverse patient groups with: 1) restrictive (interstitial lung disease [ILD]), and 2) pulmonary thromboembolic vascular disorders (post-pulmonary embolism [PE] syndrome).

The first study examined mechanisms of dyspnea in patients with ILD in comparison to healthy control participants. Dyspnea intensity increased in ILD patients during constant work rate exercise in association with a sharp increase in inspiratory neural drive (IND) (diaphragm activation) from a high resting value of 16.66±6.52% to 60.04±12.52% of maximum (r=0.798, p<0.001). To further evaluate the strength of this association, we attempted to manipulate the independent variable (IND) and conducted a randomized double-blind placebo-controlled crossover study comparing the effect of inhaled fentanyl vs placebo on dyspnea and IND during exercise. At standardized exercise time, Borg dyspnea intensity ratings with fentanyl vs placebo were 4.1±1.2 vs 3.8±1.2, respectively (p=0.174), and IND responses were also similar; pulmonary gas exchange and respiratory mechanical responses to exercise were unaltered by fentanyl. We concluded that the strong correlation between dyspnea and IND during exercise in ILD was not modified by inhaled opiates, at least under these experimental conditions.

The second study examined the relationship between dyspnea and IND during incremental exercise in patients with post-PE syndrome in comparison with matched healthy participants. Dyspnea and IND were higher at submaximal work rates vs control, and dyspnea was strongly correlated with increased IND (r=0.630, p<0.001) in the post-PE group. In addition, ventilatory inefficiency (assessed by ventilatory equivalent for CO2 [VE/VCO2]) was consistently higher in the post-PE group (VE/VCO2 nadir: 33.27±4.99 vs 27.15±2.44, p=0.002). The results suggested that increased chemo-stimulation, linked to high physiological dead space (and relatively reduced pulmonary blood perfusion), was an important contributor to increased IND and attendant dyspnea following remote PE.

Collectively, these studies extend our knowledge of the neurophysiology of exertional dyspnea in novel and diverse clinical populations. In particular, they highlight the central role of amplified IND – a major therapeutic target for dyspnea relief.

abstract: M.Sc.


title: From Alienation to Self-Realization: Pathologies of Late Modernity, Work, and the Successful Life

contributor:
Sypnowich, Christine
Philosophy

subject:
Alienated Labour
Alienation
Appropriation
Ethical Critique
Labour
Marxism
Post-Work
Self-Realization
Social Pathologies
Work

abstract: The “promise of modernity”—the capacity of individuals to lead successful lives comes under severe strain in late modernity. Adopting a formal “appropriative” model of alienated labour which is responsive to individuals’ own conceptions of the good, desires, goals, ground projects, and needs, I identify two principal obstacles to the self-realization of late-modern subjects: (i) social pathologies, which, I argue, contemporary political philosophy is unable to adequately diagnose and (ii) the tyranny of work, which remains peripheral to modern political theory. Both of these factors impede the ability of subjects to establish successful relationships to others, to themselves, and to the world and hence their capacity to lead successful lives. After exploring these in some detail, I put forward four proposals aimed at recapturing the broken promise of modernity beyond the realm of necessity. After laying out the theoretical foundations of the alienation critique (Chapter 1), the dissertation is divided into chapters that follow its novel application across the four tasks of ethical critique: (i) symptomatology and (ii) aetiology (Chapter 2), (iii) diagnosis (Chapter 3), and (iv) prognosis/therapy (Chapters 4 and 5). Chapter 1 makes the case for the appropriative model of alienated labour as the most promising candidate for the alienation critique and the one best suited to overcome the difficulties that plague traditional accounts of alienation. Part II is concerned with the critical-diagnostic dimension of the alienation critique. Chapter 2 provides an overview of the “malaises” of late modernity and discusses the aetiology of these symptoms. Chapter 3 diagnoses three social pathologies missed by current theories of justice: pathologies of individual freedom, pathologies of de-synchronization, and pathologies of organized self-realization. Part III is concerned with the prescriptive dimensions of the alienation critique. Chapter 4 argues that the appropriative model issues in a call for the “refusal of work” which attempts to chart a course beyond the work-based society and its productivist values. Chapter 5 makes the case for four proposals that aim to provide late-modern subjects with a measure of security and stability, decommodify labour, and pave the way to the realm of freedom beyond the tyranny of work.

abstract: PhD


title: Genetic and Geographic Boundaries in the Spring Peeper (Psuedacris crucifer) with Insights into Mito-Nuclear Discordance, Reticulation, Niche Divergence and Isolation

contributor:
Lougheed, Stephen
Biology

subject:
Phylogeography
Discordance
ddRAD
Contact-Zone
Ecological Niche Model

abstract:
The reduction of gene flow is often associated with divergence and initial stages of speciation. In the absence of gene flow, sister lineages should diverge genetically from one another in a roughly clock-like fashion even without divergent ecological pressures. However, the biotic and abiotic forces which underpin divergence in a species’ ecology are seldom static in space or time. Organismal adaptability and the impermanence of ecological barriers can result in the opportunity for renewed gene flow over the history of a species. Under the biological species concept this is when species boundaries are tested.  Such variable patterns of genetic exchange can leave complicated phylogenetic signals.
I investigated the spring peeper (Pseudacris crucifer), a frog that is well suited to studying the role of gene flow in speciation due to its massive geographic range and multiple parapatric lineages. I first explored the range-wide patterns of intraspecific genetic and call diversity. I then focused on one distinctive inter-lineage contact zone to quantify the patterns of gene flow and variation in call and morphological traits across it. Finally I modeled the contribution of climate, elevation and reproductive interference to the distribution of  both lineages. My work revealed patterns of phylogenetic and geographic discordance between mitochondrial and nuclear DNA, driven by the apparent widespread introgression of nuclear DNA. I also observed narrow, generally coincident clines in call and genetic traits suggesting a tension zone at one contact zone that coincides with a distinct altitudinal and climatic ecotone.
The patterns I observed in P. crucifer imply a complex relationship between environment, allopatry, divergence, and gene flow. Populations within one region (westernmost part of the species range) have diverged from populations across the remainder of species range, where  gene flow appears to be homogenizing differences in zones of contact. Pseudacris crucifer provides a compelling example of the importance of range-wide genetic studies, the complicated evolutionary histories of species that occur in areas impacted by glaciation, and the consequences of gene flow on diversification to the level of incipient species.

abstract: PhD


title: 'It is I Who Am Transforming': Mining, Capitalism, and the Conscious Earth

contributor:
Cameron, Laura Jean
Lovell, George
Geography and Planning

subject:
Mining
Capitalism
Ecopsychology
Feminist Geography
Material Geography
Resource Geography

abstract:
This dissertation is guided by one underlying research question: How does one transform an environmentally destructive society? The society in question is that of the capitalist Western world. I begin with a hypothesis: the inherent destruction of the West is rooted in perceived human-Earth disconnection; thus, the path to sustainable Earth relationships may lie in re-perceiving connection. I limit my focus to the mining industry and the rocks and minerals it commodifies. Three stages of research are undertaken. First, I explore the ontology of the West through interdisciplinary circle-talks focused on the nature of rocks and minerals (NRM). Second, I relay findings of interviews conducted with senior mining executives about their relationships with the natural world and their views on the sustainability of capitalist modernity. Finally, I propose Earth gratitude as a doorway to Earth re-connection. I explored this potentiality in the course of my research by creating an Earth Gratitude Booth (EGB) which I hosted at the 2019 Canadian Institute of Mining, Metallurgy and Petroleum convention. For all three stages of research, an ecopsychological ontology, an ontology of Earth-connection, has been incorporated.
This research initiates and unearths new and vital conversations. The NRM discussions disclose complex ontological relationships with the rock world; I suggest that the Western discourse of an objectified Earth does not well reflect the diverse ontologies of Western individuals. In the mining interviews, I encountered individuals with varying degrees of conscious Earth relationship. When asked about capitalism, not a single participant believed the system to be sustainable; indeed, many recognize the toxicity of capitalism and articulate an urgent need to change that system. Finally, the EGB highlights the challenge of ontological transformation. Some convention goers are antagonized by the EGB, and the dichotomies of male-female, mind-body, self-other are stark. However, most engagement facilitated by hosting the booth proved hopeful. I conclude that Earth gratitude may serve as a promising portal to re-perceived human-Earth connection.

abstract: PhD


title: Assessment of Local Strains in Geomembranes at Gravel Indentations

contributor:
Brachman, Richard
Civil Engineering

subject:
Geosynthetics
Civil Engineering
Geomembranes

abstract: Tensile strains that occur in geomembrane liners that are induced by local gravel indentations are investigated, with an emphasis on how the strains are calculated and what testing methods are used to obtain the deformed shape of the geomembrane. This involved the use of established test methods and apparatuses but using a 3D laser scanner to obtain the deformed shape and a recently developed theoretical technique to calculate strain in a geomembrane. Full-scale geosynthetic protection efficiency tests were conducted to test the influence of subgrade on the geomembrane strains. The subgrades examined included no subgrade, a firm rubber pad and a compacted clay liner. The results showed that the tests with no subgrade and rubber subgrades significantly overestimated and underestimated, respectively, the strain in the geomembrane when compared to results from the compacted clay liner tests. Smaller-scale index tests were also conducted to determine the ability of previously developed single-point test apparatuses to simulate the maximum, rather than mean, strain found in a corresponding full-scale test. Two apparatuses machined to simulate the average response of nominal 25 and 50 mm gravels with a single gravel particle were tested. Results showed that the strains induced in the 25 mm cell tests should be multiplied by a factor of at least 2 to reach the maximum strain in the corresponding full-scale test. The effect of strain calculation method was also investigated, where it was shown that a strain of 6% calculated using an established method considering small-displacement-membrane plus bending effects but ignores large displacement effects from lateral displacements is closer to a “true” strain of 8% when radial displacements are included providing the first quantification of simplifying calculation assumptions for actual 25 mm gravel.

abstract: M.A.Sc.


title: A One Shot Method For Estimating The Two Parameter Division Model Of Lens Radial Distortion Based On The Direct Linear Transformation

contributor:
Greenspan, Michael
Electrical and Computer Engineering

subject:
Radial Distortion Correction
Calibration
One-Shot Estimation
Direct Linear Transformation

abstract: Many computer vision algorithms assume a pinhole camera model, but commercial and off-the-shelf cameras usually exhibit enough lens distortion to violate this model. There are many methods that have been proposed to estimate radial lens distortions, each of which has specific limitations. A novel method is therefore proposed in this thesis to estimate and correct for image radial distortion. The solution is based upon an algebraic expansion of the homographic relationship between a planar pattern and its distorted projection into a single image, which is solved using the Direct Linear Transformation. The proposed method requires ten point correspondences, is fully automatic and estimates both the first two parameters of the radial lens distortion division model, and the center of distortion. Experimental results show the method to be general and practical, and more accurate than other recent one- and twoparameter point correspondence-based and plumb line-based approaches.

abstract: M.A.Sc.


title: Characterizing the Development of Secondary Hyperparathyroidism and Vitamin D Resistance in Experimental Chronic Kidney Disease

contributor:
Adams, Michael
Holden, Rachel
Biomedical and Molecular Sciences

subject:
Chronic Kidney Disease
Mineral Homeostasis
Secondary Hyperparathyroidism
Vitamin-D Resistance
Calcitriol Resistance
Pathology

abstract:
The parathyroid gland (PTG) responds to alterations in calcium and phosphate via secretion of parathyroid hormone (PTH) that acts on kidneys and bone to regulate mineral homeostasis. Hallmarks of chronic kidney disease (CKD) include increased retention of phosphate (PO4) and decreased renal production of 1,25-dihydroxyvitaminD3 (calcitriol) from its precursor, 25-hydroxyvitaminD3 (calcifediol). Hyperphosphatemia and vitamin D deficiency in CKD stimulate excessive production and secretion of PTH, generating maladaptive consequences to the structure and function of bone and blood vessels, pathologies that are associated with increase mortality in the CKD population.

Calcitriol is a mainstay therapy for the treatment of secondary hyperparathyroidism (SHPT) that develops in CKD. A major issue with therapy includes the development of calcitriol resistance and increased vascular calcification. Modifications to the PTG that hinder its sensitivity to calcium (Ca) and PO4 are hypothesized to be involved in the development of calcitriol resistance, renal osteodystrophy, and vascular calcification in SHPT which is associated with increased risk of bone fracture and cardiovascular burden. The research contained herein, involving in vivo animal studies as well as in vitro isolated PTG studies, sought to characterize the development of calcitriol resistance and SHPT in CKD, particularly with regard to changes in response mediated by excess PO4.

The major findings indicate that high dietary PO4 attenuates calcitriol mediated suppression of PTH to acute and chronic treatment of calcitriol. Calcitriol treatment (CTx) in both CKD and non-CKD animals showed reduced gland responsiveness and persistent lowering of basal PTH secretion in vitro.

Overall the findings emphasize the clinical significance of PO4 restriction for enhancing the effectiveness of strategies that target PTH lowering and suggest caution in the use of calcitriol for the treatment of SHPT. A common approach for management of calcitriol resistance is to increase doses of calcitriol during therapy. This should be avoided as prolonged treatment appears to be able to persistently impact PTG response to alterations in Ca and PO4 both in non-CKD and experimental CKD animals resulting in impaired mineral homeostasis.

abstract: M.Sc.


title: “What’s love got to do with it?” Race, Gender, Nation and the Criminalization of Polygamy in Canada and the United States.

contributor:
McKittrick, Katherine
Gender Studies

rights: Attribution-NonCommercial-NoDerivs 3.0 United States

subject:
Polygamy
Gender Studies
Feminist Theory
Settler-Colonialism
Law and Legal Theory
Critical Race Studies

abstract: This project interrogates the weaponization of heteronormative marriage in processes of state formation and in relation to practices of polygamy. This dissertation explores how gender and race have been used at the service of the white settler-colonial state via the criminalization of polygamy; and, the role of law, policy, and science in the contemporary construction and perpetuation of normative gender roles and racial hierarchies which rely on the primacy of monogamous marriage and the criminalization of polygamy to remain coherent. Engaging with  bodies of theoretical work that highlight how polygamy has been and continues to be utilized in a myriad of processes including normative constructions of the family, nation building, the state and citizenship; race and racism; sexuality; and gender equality, this dissertation investigates and interrogates struggles over the meaning and representation of polygamy at the intersection of history, law, and culture.

abstract: PhD


title: A Subjective Measure of Attitude Extremity: Validation and Extension

contributor:
Fabrigar, Leandre R.
Psychology

subject:
Attitudes
Persuasion
Social Psychology
Attitude Extremity

abstract:
Attitudes are individuals’ enduring global evaluations of objects, concepts, or ideas, which may vary in both valence and extremity. There are many important determinants of attitudes and attitude strength, with research suggesting that one important determinant is the extremity of one’s attitude. The present research explored two possible methods of capturing individuals’ attitude extremity through objective and subjective measures. The goal of the current research was therefore to test two propositions: First, that the measures should be largely independent of one another, and second, that each measure would tap into meaningful processes of the functioning of the attitude.
Study one examined the role of objective and subjectively measured attitude extremity on resistance to persuasion attempts. Here, we found that the measures were modestly correlated to one another, and that both exerted independent and opposite effects on persuasion resistance. Study two examined the role of subjective and objectively measured extremity on information processing. We again found modest correlations between the measures, though each measure produced minimal effects on information processing. The exception to this was our finding that individuals’ attitudes affected the favorability of their thoughts, and that this effect was more pronounced for objectively extreme attitudes. We discuss implications for this research in the context of the broader attitude strength literature and future directions for this work.

abstract: M.Sc.


title: Cognitive Performance in Geriatric Depression: Examining the Sensitivity of Clinical Neuropsychological and Experimental Working Memory Tasks

subject:
Cognition
Major Depressive Disorder
Geriatric Depression
Cognitive Impairment

abstract: Background: Traditional neuropsychological measurement tools have identified a proportion of individuals with late life Major Depressive Disorder (MDD) who experience modest to moderate cognitive impairments. These cognitive impairments are associated with impairments in everyday functioning. However, a large proportion of individuals with MDD report difficulties with cognition that are greater than those identified with traditional measurement tools. In this study, we explore cognitive performance using new methods that are different from those used in traditional cognitive testing. We aim to test if rather than using traditional measures of cognitive abilities, cognitive performance impairments in MDD reveal themselves as a function of increasing complexity of cognitive tasks, and to examine the relationship of cognitive performance on these tasks to everyday functioning. Method: Older participants with remitted MDD (MDD-R; n = 93), Mild Cognitive Impairment (MCI; n = 200), MCI with comorbid MDD-R (n = 80), and healthy comparison participants (n = 53) completed a baseline neuropsychological assessment battery for preventative intervention for Alzheimer’s Dementia for individuals at clinical risk were used in analyses. We examined group differences in cognitive performance accuracy across three experimental working memory tasks that allowed for titration of complexity (i.e., the Paced Auditory Serial Processing Task (PASAT), n-back, Continuous Performance Task – Identical Pairs (CPT-IP)). Changes in performance over the course of the cognitive tasks were entered into a regression equation to examine the variance accounted for above and beyond global cognition in predicting everyday functioning in all clinical groups. Results: Relative to healthy comparison participants, individuals with MDD-R had significantly worse performance on all levels of the PASAT and n-back tasks. The MDD-R group performed significantly better than the MCI groups on all levels of the PASAT and n-back. No significant group differences were found on the CPT-IP. Changes in PASAT performance were significantly associated with everyday functioning but did not add meaningful variance in understanding the relationship between cognition and everyday functioning. Conclusions: Our findings highlight the utility of using novel methods to probe cognition, such as the experimental cognitive tasks with the ability to titrate complexity used in this study, in late life MDD.

abstract: M.Sc.


title: Fura-2 Calcium Imaging Is a Valid Method of Investigating Signalling & Integrative Properties of the Subfornical Organ

contributor:
Ferguson, Alastair V
Neuroscience Studies

subject:
Subfornical Organ
Fura-2
Angiotensin
Cholecystokinin
Neuroscience
Circumventricular Organs
Calcium Imaging
Methods
Type 2 Diabetes
Homeostasis
Hyperglycemia

abstract: Research into the integration of signalling molecules at the subfornical organ (SFO) is typically conducted through in vitro electrophysiology methods on dissociated SFO neurons. We performed Fura-2 calcium imaging on dissociated SFO neurons and compared our observations to past electrophysiology data to determine if our imaging protocol can be used as an alternative, high-throughput method to investigate the integrative properties of the SFO. Sequential bath-application of 10-8 M cholecystokinin (CCK), a signalling molecule involved in energy balance, and 10-8 M Angiotensin-II (ANG), an excitatory signalling molecule involved in fluid balance, was performed on dissociated SFO neurons in hypoglycemic (1 mM glucose), normoglycemic (5 mM glucose), and hyperglycemic (10 mM glucose) conditions. ANG caused an increase in intracellular calcium ([Ca2+]i) in 32.8% (n = 20/61), 53.7% (n = 29/54) and 69.8% (n = 30/43) of SFO neurons at 1, 5 and 10 mM glucose, respectively, which is similar to the proportion of SFO neurons which depolarized to ANG in electrophysiology experiments [33.3% (n = 4/12) at 1 mM, 50.0% (n = 16/32) at 5mM, and 72.7% (n = 8/11) at 10 mM glucose]. These results suggest that ANG-related depolarizations and detectable [Ca2+]i increases are associated with each other. CCK caused an increase in [Ca2+]i in 31.1% (n = 19/61), 35.2% (n = 19/54), and 44.2% (n = 19/43) of SFO neurons at 1, 5 and 10 mM glucose, respectively, which is similar to the overall proportion of CCK-responsive neurons in electrophysiology experiments [41.2% (n = 7/17) at 1mM, 48.9% (n = 22/45) at 5 mM, and 47.6% (n = 10/21) at 10 mM glucose]. CCK elicits both excitatory and inhibitory responses, so our results suggest that increases in [Ca2+]i may be associated with both types of events. Lastly, we observed four subpopulations of SFO neurons: those who respond exclusively to ANG (n = 48/158), those who respond exclusively to CCK (n = 26/158), those who respond to both peptides (n = 31/158), and those who respond to neither peptide (n = 53/158). The observation of four subpopulations aligns with past electrophysiological data. Overall, our results suggest that SFO neurons respond to ANG and CCK similarly in imaging and electrophysiology trials and that Fura-2 calcium imaging is a reliable high-throughput method for researching signal transduction and the integrative properties of the SFO.

abstract: M.Sc.


title: Computational Modal Analysis of Prestressed Half Scale Generic Business Jet Substructures

contributor:
Mechefske, Chris
Mechanical and Materials Engineering

subject:
Computational Modal Analysis
Finite Element Method

abstract: Computational modal analysis via finite element analysis is a well-established method for modal parameter estimation. The resultant modal parameters are crucial inputs for vibro-acoustic finite element analyses and require accurate modal models. The work presented here aims to provide insight into the techniques necessary to model business jet fuselages with prestressed skin panels through computational modal analysis of two substructures of a generic business jet design. The two substructures were assembled under manufacturing limitations which resulted in bending pre-stress within skin panels. The effect of bending pre-stress in skin panels was empirically determined through the use of experimental modal analysis of two geometrically similar assemblies with differing levels of bending pre-stress. This study found bending pre-stress in flat plates to increase natural frequencies while having a negligible effect on mode shapes. Preliminary computational modal analysis models of the substructures were developed without accounting for pre-stress to determine the significance of internal loading. These results revealed that pre-stress was only significant in one of the substructures. Furthermore, pre-stress effects were found to only be significant when skin resonant modes were present. A unique model updating technique was introduced to provide the same effects as bending pre-stress. The robustness of this technique to various design changes was tested via a sensitivity analysis. This test confirmed that the technique was effective in providing a consistent increase in skin natural frequencies without changing mode shapes. This test also revealed that the technique is limited in bandwidth depending on the design. The updating technique was applied to the substructure model that was previously confirmed to suffer from significant pre-stress effects. The updated model improved the natural frequency and mode shape correlation across all metrics. A frequency response analysis was performed on the updated model to provide further validation of the technique and model. The computational frequency response analysis provided sufficient proof that the updated model produced improved frequency response plots when compared to the preliminary model.

abstract: M.A.Sc.


title: Factors Controlling Tungsten Mobility in W-Cu Skarn Tailings from the Cantung Mine, Northwest Territories, Canada

contributor: Geological Sciences and Geological Engineering

subject:
Tungsten
Environmental Geochemistry
Mine Waste
Tailings
Cantung Mine
Scheelite

abstract:
Few studies have addressed the mobility of tungsten in mine waste, which could act as a point source for metal leaching. This study addresses the behaviour of tungsten in tailings at the Cantung Mine in the Northwest Territories, Canada. In addition to this study, this thesis includes a literature review regarding the environmental geochemistry of tungsten.
	In the Cantung tailings, tungsten is present as scheelite (CaWO4; 0.1 – 0.7 wt.%), copper is hosted in chalcopyrite (CuFeS2; 0.1 – 1.5 wt.%), and gangue mineralogy consists of abundant pyrrhotite (Fe1-xS; 0.2 – 49 wt.%), calc-silicate minerals (26 – 62 wt.%), and carbonate minerals (0 – 30 wt.%). In July 2018, nine surface water samples, five tailings pore-water samples, and thirteen tailings samples were collected from the Cantung Mine’s tailings. Water samples have been analyzed by high resolution inductively coupled mass spectrometry (HR-ICP-MS), yielding tungsten concentrations ranging from 5.3 to 26.3 μg/L, exclusively in samples with pH values between 7.05 – 8.05. Tungsten and iron concentrations are both on average 1.6 x higher in unfiltered aliquots compared to filtered aliquots, suggesting that tungsten is transported as dissolved species but is also adsorbed to suspended Fe-oxyhydroxide minerals. Tailings were analyzed by scanning electron microscopy (SEM) paired with automated mineralogy software (MLA), synchrotron-based μXRD-XRF, and partial leach extractions. The scheelite content of Tailings Pond 3 (TP3) and the FRT are similar (0.15 wt.% and 0.21 wt.%, respectively), and scheelite shows no evidence of alteration. Synchrotron-based μXRD of Fe-oxyhydroxide minerals in the FRT identify goethite (FeOOH) and lepidocrocite (γ-FeOOH), whereas μXRD spectra of pyrrhotite rims from TP3 do not match Fe-minerals, with the exception of rare rims that match hematite (Fe2O3) and maghemite (γ-Fe2O3). The μXRF maps of the hematite-maghemite rims have prominent tungsten peaks, which represents included scheelite grains and possibly structurally incorporated tungsten, likely formed during ore processing. The hydroxylamine leaches yield higher tungsten concentrations in tailings samples from the impoundments than samples from the FRT, suggesting the tailings impoundments have more tungsten that is associated with poorly crystalline and amorphous Fe-oxyhydroxide phases than the FRT. Over time, labile-hosted tungsten in the FRT may have been washed down the Flat River during Fe-oxyhydroxide recrystallization and high energy flooding events.

abstract: M.Sc.


title: Exploring Indigenous Social Capital and Health Among Four First Nations: A Strengths-Based Study

contributor:
Castleden, Heather
Rosenberg, Mark
Public Health Sciences

subject:
Social Capital
Indigenous Health
Strengths-Based Research
Community Health
Canada

abstract: The impact of social networks and relationships on health outcomes has been acknowledged and studied within the concept of “social capital” in the field of public health for over two decades. To date, however, few research studies have included Indigenous peoples, and even fewer have focused on the unique strengths that Indigenous social environments bring to health and well-being. In view of these observations, the goal of my thesis is to explore the concept of social capital and its effects on health within Indigenous paradigms of community, health, and wellness. This thesis is framed around a mixed methods study, drawing from a survey that was conducted as part of the Canadian Alliance for Healthy Hearts and Minds study, as well as from interviews with members of Pictou Landing First Nation. Together, the findings of this study suggest that individual Indigenous communities possess unique stocks of social capital that are distinct from one another, as well as fundamentally different from those of non-Indigenous communities. This study also identifies the intimate relation between the construction of social capital and cultural ontologies, histories, and identities, and challenges the use of non-Indigenous (or pan-Indigenous) metrics of social capital in health research. Ultimately, this study calls for stronger consideration of Indigenous social capital as an asset in public health and health promotion involving Indigenous peoples and communities.

abstract: M.Sc.


title: Developing Better Models for Dialogue Threads and Responses

contributor:
Zhu, Xiaodan
Electrical and Computer Engineering

subject: Dialogue System

subject: Response Selection

subject: Multiple Participants

subject: Dialogue Disentanglement

subject: Deep Contextualized Utterance Representations

subject: Natural Language Processing

abstract: In this thesis, we focus on developing machine learning algorithms to model human dialogues and conversations by investigating three basic tasks. We first study the development of retrieval-based chatbots, in which the models aim to recommend the most appropriate responses for users based on the dialogue context. We propose a pretrained-based SA-BERT method to incorporate the identities of speakers which outperforms all existing models on four benchmark datasets. In the second task, we aim to help users to better access the dialogue history by proposing novel models for dialogue disentanglement. Specifically, multiple threads of discussions in the same dialogue are disentangled and organized to single topic threads. This research can help users to more easily follow up on the topics discussed in complex dialogues. We propose a hierarchical model by considering both single utterance and context semantics, which achieves new state-of-the-art performance on two datasets. In the third task, we are concerned with the outcome of dialogues --- determining if users' questions or problems have been addressed or answered in a dialogue, and if so, where they are addressed in the dialogue. Different from the previous study in which the contribution of each utterance towards the outcome is a black-box, we perform a pilot study by adding interpretability through determining if each utterance is contributing to addressing the user's questions. Our attention-based model is shown to achieve the best-reported performance on the evaluation dataset.

abstract: M.A.Sc.


title: An Investigation of the Susceptibility of Acrylic Emulsion Paints to Biodeterioration by Mould: Developing a Methodology for the Study of Microbial Activity on Modern Paints

contributor:
Murray, Alison
Smithen, Patricia
Art Conservation

subject:
Mould
Biodeterioration
Acrylic Emulsion Paint
Relative Humidity
Water Activity
Art Conservation
Synthetic Polymers

abstract: The biodeterioration of cultural heritage is a considerable concern for cultural institutions as the material variety within heritage objects provides diverse ecological niches for microorganisms to colonize. Due to limited prior studies, little is known about the vulnerability of acrylic emulsion paints, and other synthetic materials, to microbial colonization as these materials have been incorrectly assumed to be resistant to biological attack. This study presents an initial investigation of the susceptibility of acrylic emulsion paints to mould growth under different environmental conditions and seeks to develop a simple protocol for the study of mould growth on modern paints. Fresh acrylic paint films, both clean and artificially soiled, were inoculated with mould species and subjected to different relative humidity conditions for a thirty-one-day incubation period to determine the optimal conditions that support microbial growth. Results indicated that atmospheric relative humidity and the related paint film water activity (aw) are key factors in increasing the film’s susceptibility to mould growth, as those incubated in higher relative humidity environments were observed to have higher water activity levels and more evidence of mould growth. Mould growth was also observed on artificially soiled films, indicating the importance of a nutrient source on the film’s susceptibility to mould; however, results further indicated that some pigments and paint additives can act as a nutrient source, thus increasing film susceptibility. Conversely, other factors, such as paint film pH and specific mould species, were not found to have as significant an impact on film susceptibility. Protocols for research concerning mould on modern paints were proposed based on the results of this study. The results of this study provide a necessary foundation for the continued study of biodeterioration of acrylic emulsion paints.

abstract: M.A.C.


title: Exploring the Relationship Between Teachers’ Formative Classroom Assessment Practices and Students’ Self-Regulation in Kindergarten Classrooms

contributor:
DeLuca, Christopher
Education

subject:
Formative Assessment
Kindergarten
Self-Regulation

abstract: A concurrent mixed methods study design was used to explore possible relationships between teachers’ formative classroom assessment practices and students’ self-regulation in Kindergarten classrooms. A total of 8 female Kindergarten teachers and 80 students from diverse learning backgrounds were recruited to participate in this study. Data collection was conducted across two time periods (January through March 2019 and April through May 2019) and separated by 12 weeks. Data were collected using classroom observations, teacher ratings of students’ self-regulation, teacher interviews, field notes, and self-regulation tasks administered to students. A total of 448 hours were spent across eight classrooms with 56 hours in each classroom. All quantitative data were analyzed using SPSS through descriptive and inferential statistics. All qualitative data were analyzed thematically to identify emergent themes across the data. Results indicated that the most commonly observed and reported assessment practices included descriptive feedback, anecdotal notes, and observations. However, a greater volume of assessment practices conducted by teachers did not result in greater development of students’ self-regulation. Generally, self- regulation scores increased for students at Time 2 for all 3 self-regulation student measures. Teachers’ assessment practices tended to be teacher centric with little implementation of more contemporary practices, such as peer- and self-assessment and questioning. At times, teachers demonstrated using assessment to promote self-regulation, however, the focus was on behavioural and emotional regulation with little consideration for the cognitive domain. All teachers agreed that self-regulation required vast support, including strategies such as modelling and co-regulation. A reconceptualization of assessment at the Kindergarten level is necessary to support the development of self-regulation and encourage student agency to the greatest extent.

abstract: PhD


title: Investigating the Role of Dopamine in Opioid Reward in Chronic Neuropathic Pain

contributor:
Olmstead, Mary
Psychology

subject:
Neuropathic Pain
Opioid Reward
Chronic Pain
Dopamine
Reinforcement
Analgesia
Addiction

abstract: Background: Neuropathic (NP) pain is commonly treated with opioids, such as morphine, despite acknowledgement that these drugs produce long-term complications including tolerance and addiction. Opioids have two effects on NP pain: they reduce negative sensations (i.e., pain relief) and produce positive affect (i.e., reward). The latter, mediated through the mesolimbic dopamine (DA) pathway, is linked to the addictive potential of commonly misused drugs. The goal of this project was to examine DA mechanisms in the positive and negative reinforcing effects of opioids in chronic NP pain. Methods: NP pain was induced in male Long-Evans rats using chronic constriction injury (CCI) of the sciatic nerve. A one-sided conditioned place preference (CPP) paradigm provided independent measures of positive and negative reinforcement. NP and sham-lesioned rats (6-13 days post-surgery) underwent four CPP conditioning sessions, every other day, in which they were confined to either a morphine- or saline-paired compartment for 30 min. On intervening days, they received the alternate injection and were left in the home cage. On test day, drug-free rats had free access to all compartments for 30 min: increased time spent in the drug-paired compartment reflects a CPP whereas decreased time spent in the saline-paired compartment reflects a conditioned place aversion (CPA). The role of DA mechanisms in CPP and CPA was assessed in separate groups of rats that received injections of the non-specific DA antagonist, flupenthixol, prior to morphine injections. Results: NP rats showed a CPA to the vehicle-paired (i.e., pain-paired) side, whereas sham-lesioned rats did not. A low dose of morphine reduced the CPA (negative reinforcement), which was not blocked by DA antagonism. A higher dose of morphine produced a CPP (positive reinforcement), which was blocked by DA antagonism at a lower dose in sham-lesioned compared to NP rats. Conclusions: The positive and negative reinforcing effects of opioids may be differentially mediated in chronic NP pain. In addition, opioids may be more rewarding in chronic NP pain states, possibly due to the combination of positive and negative reinforcement.

abstract: M.Sc.


title: Prison and its Afterlives: Haunting and the Emotional Geographies of Formerly Incarcerated People’s Reintegration Experiences in Kingston, Ontario, Canada

contributor:
King, Samantha
Kinesiology and Health Studies

subject:
Prison
Haunting
Emotional Geographies
Incarceration
Reintegration
Risk
Kingston

abstract: Kingston is undeniably a prison town. As the venue for Canada’s first prison and current home to nearly twenty percent of the nation’s federally incarcerated people in seven penitentiaries around the city, prisons undoubtedly influence the economic, political, and social life of Kingston. While Kingston’s identity as a prison town is touted by the local municipality as beneficial for the community, people who have been incarcerated and released into Kingston have a different story to tell. Reintegration – the process of leaving prison and re-entering the community – is inevitable for the majority of incarcerated people in Canada. However, people who are released from prison into Kingston have reported significant difficulties maintaining lasting or successful reintegration despite the overwhelming presence of local prisons, their supporting administration, and an extensive network of non-profit and charitable service providers. Reintegration into the community is not only a physically exhausting experience, but one that is emotionally fraught with feelings of anticipation, uncertainty, fear, anger, and boredom. Based on twenty-three interviews with formerly incarcerated people in Kingston, I argue that attending to the emotional geographies of reintegration in Kingston, where people both struggle with and resist violent reintegration discourses of risk and responsibility, is critical to developing a more equitable reintegration praxis. I contend that understanding how people with prison experiences feel in the community not only brings the ethics of current reintegration practices into question; it also reveals how neoliberal discourses of risk and responsibility extend beyond the walls of the prison, prolonging the haunting effects of the settler-colonial carceral state in the everyday lives of formerly incarcerated people.

abstract: M.A.


title: A Comparison of Ancient Roman Justice Systems and Canadian Indigenous Justice Systems: Approaches to Crime and Punishment

contributor:
Fabio, Colivicchi
Kelly, Olson
Classics

subject:
Roman Law
Canadian Indigenous Law
Criminal Law

abstract: Canadian law is legally pluralistic and combines common law, civil law, and Indigenous legal traditions. Roman law has contributed largely to both the Canadian common law and civil law traditions while Indigenous law has developed from its own belief system and history. Conflict has arisen within Canada’s criminal system with respect to Indigenous offenders due to the retributive nature and positivistic approaches of both the common law and civil law systems in the face of the restorative methodology found in Indigenous approaches to crime. The retributive approach is largely reflective of the legal ideology developed by the Romans and their methods for punishing crime. However, Rome had many different periods of law and the history of Roman law before the classical period has largely been ignored in legal scholarship. By contrasting the two systems, I argue that criticism for Indigenous law as being largely custom is misplaced and that Indigenous law derives force from similar sources of law found in the Roman system. Moreover, I argue that the overincarceration and representation of Indigenous individuals within the Canadian criminal system is partially the result of differences in core values resulting from separate histories and customs. The Canadian criminal system may benefit from adopting smaller organizational structures in order to provide more personal services as is seen in Indigenous systems. Furthermore, the Canadian criminal law system needs to incorporate further aspects of Indigenous law into its structure which represent traditional Indigenous values in order to encourage reconciliation and help heal Canada’s Indigenous peoples. However, this presents difficulties given the sizeable population of modern cities and the needs of administering justice over a large population.

abstract: M.A.


title: The Effect of Soil Gradation and Addition of Natural Fibres on the Mechanical Properties and Freeze-Thaw Durability of On-Site Manufactured Compressed Earth Blocks

contributor:
Green, Mark F.
Civil Engineering

subject:
Compressive Strength
Flexural Strength
Indigenous Housing
Natural Fibres
Compressed Earth Blocks
Cold Climates

abstract:
Implementation of sustainable materials is becoming an imperative consideration in modern building because of the impact of the construction industry on climate change patterns. Building with earth is an ancient technique common in many warm regions and developing countries due to its low cost, and is garnering attention for applications in cold regions due to its favorable hygrothermal properties, ease of use, and low embodied energy.
The compressed earth blocks (CEBs) in this project were manufactured on-site by an experienced builder in Cobourg, Ontario, Canada using a combination of various soil gradations and locally sourced natural fibres (Phragmites, straw, switchgrass, and rice hulls). Approximately 280 CEBs were tested in direct compression and three-point bending at ambient conditions, saturated conditions, and after being subjected to six and twelve freeze-thaw conditioning cycles.
Results showed that blocks constructed with about 20% gravel particles had up to a 29.3% increase in compressive strength and up to a 71.4% increase in flexural strength than blocks constructed with soil containing only sand, silt, and clay particles.
The addition of natural fibres was more beneficial for the compressive strength. In general, blocks produced with the larger quantities of fibres had significantly reduced compressive and flexural strengths than the blocks produced with lower quantities of fibres. The addition of 0.5% of Phragmites fibres resulted in a strength of 7.5 ± 0.34 MPa when added in combination with the gravel particles. The corresponding flexural strength of this block type was 1.56 ± 0.36 MPa which was 11.4% less than the flexural strength obtained using gravel particles and no fibres. Blocks produced with 0.125% straw achieved the highest compressive strength of 8.96 ± 0.71 MPa and blocks produced without fibres had the highest flexural strength of 1.34 ± 0.23 MPa of that investigation.
After subjecting the CEBs to six and twelve freeze-thaw cycles, the blocks showed strength retentions of up to 140% for both the compressive and flexural strengths. The moisture absorbed by the blocks during the cycling process appeared to have allowed for additional curing of the blocks, resulting in the increased capacity of the CEBs.

abstract: M.A.Sc.


title: Photoisomerization and Optoelectronic Properties of Organoboron Compounds

contributor:
Wang, Suning
Stamplecoskie, Kevin
Chemistry

subject:
Photochemistry
Organoboron Compounds
Material Science
TADF Emitters

abstract:
This thesis focuses on the investigation of the photo-induced isomerization of organoboron compounds, as well as their optoelectronic properties. Despite extensive explorations in the relationship between molecular structure and their photoreactivity, only a limited number of photoisomerization pathways have been developed. To further push the boundary in the field of N,C-chelate organoborate photochemistry, a new class of organoboron compounds has been studied, aiming to investigate the influence of both aryl substituents on the boron center and chelate backbone on their photoreaction outcomes.
B(npy)Ar2 (npy = 2-(naphthalen-1-yl)pyridine) compounds bearing various non-bulky aryl groups have been found to undergo a clean and sequential two-step photoisomerization in which two aryl substituents on boron migrate to a carbon atom of the naphthyl moiety. The 2nd isomerization step is the first example of a reversible photoisomerization between a borepin and borirane. Both steric and electronic factors have been found to have a great impact on this photoreactivity. Furthermore, the borirane isomer reacts with oxygen, forming a rare oxaborepin dimer. When these BN-heterocycles bear two different aryl groups at the boron core, they undergo regioselective photoisomerization, generating borepin species with migration of the less bulky aryl groups exclusively. In some cases, further isomerization generates the corresponding borirane diastereomer pairs with concomitant formation of two chiral centers. Significantly, the boriranes involving a 3-thienyl substituent on boron were found to thermally convert to BN-fluoranthene annulated boratapentalene via an unprecedented reversible boratacyclopropane-boratacyclopentene rearrangement. Moreover, changing the pyridyl donor to a thiazolyl donor on boron was found to provide B(naph-thiazolyl)(Mes)2 compounds a distinct new photoisomerization pathway, forming new blue fluorescent polycyclic azaborinine species instead of borepins.
Lastly, a series of butterfly-shaped organoborates with an N^C^N chelate ligand has been found to demonstrate unique photophysical properties such as thermally activated delayed fluorescence regardless the electron donating ability of the aryl group on the boron center.

abstract: PhD


title: Investigating Whether Epigenetic Changes Occur Following Gestational Exposure to Triphenyl Phosphate in C57Bl/6 Mice

contributor:
Winn, Louise
Environmental Studies

subject:
Environmental Studies
Flame Retardants
Toxicology
Reproductive Toxicology
Epigenetics

abstract: Triphenyl phosphate (TPP) is a chemical flame retardant and plasticizer which is added to both consumer and industrial products. While overt toxicity to TPP is relatively low, recent studies have begun to investigate the potential for TPP to act as an endocrine disrupting chemical causing long-term impacts on metabolism. The developmental origins of health and disease postulates that in utero exposures can have later in life effects on the developing fetus. While it has been shown that the maternal environmental, including chemical exposures, can affect fetal gene expression though the mechanism of action of this is still unclear. The aim of this research was to determine whether in utero TPP exposure in mice induced epigenetic changes which could contribute to potential alterations in fetal gene expression, and whether these changes were dose and/or sex-dependent. Pregnant C57Bl/6 mice were treated with 0, 5, 25 or 50 mg/kg of TPP on gestational days 8, 10, 12 and 14 via intraperitoneal injection before euthanization on gestational day 19. Fetal livers were collected and half of the liver was used for immunoblotting to assess changes in histone 3 acetylation, histone 4 hyperacetylation, monomethylation of histone 3 at lysine 9 and trimethylation of histone 3 at lysine 9. The other matched liver half was used to measure global DNA methylation levels using a plate assay. Results showed that there was a significant decrease in fetal DNA methylation following exposure to 50 mg/kg TPP in utero compared to the control independent of the sex of the fetus. There were no significant alterations in any histone modifications at any dose or sex following in utero TPP exposure. These results suggest that epigenetics is a viable pathway to induce changes in gene expression; however further investigation regarding the endocrine disrupting ability of TPP is required.

abstract: M.E.S.


title: On the Maintenance of Crowdsourced Knowledge on Stack Overflow

contributor:
Hassan, Ahmed
Computing

rights: Attribution-NonCommercial-ShareAlike 3.0 United States

subject: Knowledge Sharing, Knowledge Maintenance, Stack Overflow, Empirical Software Engineering, Mining Software Repositories

abstract: The enormous quantity of software artifacts (e.g., code, documentations, and online discussions) created by developers are in great need for maintenance. Among software artifacts built by developers, Stack Overflow, a question answering (Q&A) website for sharing programming knowledge, has tripled the number of its hosted answers from 9.3 million to 27.2 million over the past 6 years (as of 2019). Such a large-scale knowledge base (including code snippets along with the embedded knowledge in the question answering activities), is inevitably changing over time. In an effort to better understand the current knowledge maintenance practices and to improve the maintenance of such valuable knowledge on Stack Overflow, this PhD thesis empirically studies the Q&A activities on Stack Overflow over a decade (i.e., from 2008 to 2018). Our goal is to provide developers with lessons about the knowledge maintenance practices on Stack Overflow. Specifically, this thesis mines the question answering activities on Stack Overflow along three dimensions: 1) the obsolescence of answers, 2) the informativeness of comments that are associated with answers, and 3) the retrieval of information in hidden comments. First, we wish to understand the knowledge maintenance practices by studying obsolete answers. For example, obsolete answers can contain invalid links, or obsolete Application Programming Interface (API) usages. Secondly, we investigate the informativeness of comments that are associated with Stack Overflow answers. An informative comment can provide additional explanations, thus updating its associated answer. Furthermore, we examine comments that can be added long after an answer is posted. In particular, we study the comment organization mechanism and analyze whether hidden comments are informative as well. By empirically studying such crowdsourced knowledge, we wish to highlight the importance of maintaining such valuable crowdsourced knowledge and to understand developer practices.

abstract: PhD


title: Exploring the Role of Oxytocin in Rodent Defensive Behaviours

contributor:
Menard, Janet
Psychology

subject:
Defensive Behaviours
Oxytocin
Animal Models of Anxiety
Social Buffering
Lateral Septum

abstract: Although evidence implicates oxytocin (OT) in anxiety regulation, little is known about where this occurs in the brain or if this system is altered by social affiliation. I hypothesized that infusions of OT into the lateral septum (LS), a brain structure implicated in anxiety, would decrease rats’ anxiety-related defensive responses. Twenty male rats were administered bilateral injections of OT or saline into the LS before undergoing the elevated plus-maze (EPM) and novelty-induced suppression of feeding test (NSFT). OT infusions marginally increased the percentage of time spent on the open arms in the EPM. Surprisingly, in the NSFT novel-cage test, OT-treated rats began consuming the wafer later than controls. Thus, the effects of OT infusions on anxiety appeared test-specific. In Experiment 2, I hypothesized that social housing would reduce rats’ defensive behaviours and that this effect would map onto an increase in the functionality of the OT system, as indexed by a higher number of OT-immunoreactive (-ir) cells in the hypothalamic regions where OT is predominantly produced; i.e., the paraventricular nucleus (PVN) and supraoptic nucleus. Twenty male rats were either single- or pair-housed for five weeks, then anxiety was measured using the EPM and a modified NFST. One week later, their brains were processed for OT-immunoreactivity. Pair-housed rats took less time to initiate consumption of the wafer in the NSFT, but their behavioural profiles in the EPM did not differ from those of single-housed rats. Relative to single-housed rats, pair-housed rats had more OT-ir cells in the ventral parvocellular region of the PVN, which correlated negatively with their latency to begin consuming the wafer on Day 1 of the NSFT. These findings suggest that social housing upregulates the OT system which, in turn, influences rats’ defensive behaviours. Overall, my findings confirm the involvement of OT in behavioural defense regulation however, further research is needed to understand how OT influences defensive behaviours under different threat contexts.

abstract: M.Sc.