VictorJuiz/thesis huggingface dataset:
Dispersal, Connectivity, and Population Genetic Structure in the Sea
Keywords: biophysical modeling
marine invertebrate
seascape genomics

The spatial distribution of genetic variation across landscapes is influenced by physical features that facilitate or restrict movement and natural selection driven by environmental heterogeneity. Many marine organisms undergo a pelagic larval stage, during which time ocean currents influence dispersal and the degree of gene flow. Furthermore, gradients in temperature, salinity, and other environmental conditions produce spatially varying selection pressures across species ranges. In the first part of my thesis, I offer a novel perspective for marine conservation that emphasizes the importance of considering both connectivity (where connectivity is maintained by dispersal) and the potential for marine populations to adapt to their environment. To do so, I highlight how genomic data can be used to infer population connectivity (i.e. based on neutral genetic variation) and environmental selection (i.e. based on putatively adaptive genetic variation) in the context of marine reserve networks. Next, using a genomic dataset derived from restriction-site associated DNA sequencing (RADseq), I investigated the impact of ocean currents and environmental variables on spatial patterns of neutral and adaptive genetic variation in the commercially harvested giant California sea cucumber (P. californicus) along the northeastern Pacific coast. The results showed evidence for population structure despite the potential for widespread gene flow, and demonstrated that accounting for directionality of ocean currents explained genetic variation better than between-site geographic distances. Strong associations between sea bottom temperature and putatively adaptive loci were identified at a broad spatial scale, as well as moderate evidence that surface salinity and bottom current velocities contribute to regional patterns of adaptive differentiation. In a study using simulations of larval dispersal coupled with demo-genetic simulations, I found that potential dispersal was spatially restricted with shorter pelagic larval duration (PLD), but there was no difference between a model of diffusive (isotropic) larval transport and oceanographic (anisotropic) transport. However, several important caveats were highlighted that should be addressed in future work. Collectively, my thesis integrates genomic, environmental, and oceanographic data to understand the role of seascape features on connectivity and adaptation, with implications for marine conservation plans that aim to connect marine populations and support adaptive responses to environmental change.
Long-Term Memory Biases Auditory Spatial Attention: Healthy and Impaired “Memory-Guided Attention”
Keywords: Apolipoprotien E4
Attention
Auditory
Memory

Attention and memory may be impaired in individuals at-risk for Alzheimer’s disease (AD), though standard cognitive assessments typically study the two in parallel. In reality, attention and memory interact to facilitate processing, and thus a more integrative approach is required. Here, I used a novel auditory paradigm to assess how long-term contextual memory facilitates detection of an auditory target in healthy young adults (Study 1 and 2), and whether performance on this task is related to Apolipoprotien E4 (APOE4) genotype, a risk factor for the sporadic AD (Study 3). During an initial familiarization task, participants heard audio-clips some of which included a lateralized target (p = 50%). On each trial, participants indicated whether the target was presented from the left, right or was absent. Following a retention interval, the same audio-clips were presented, but now all included a target. Across three experiments in Study 1, young adults showed memory-based gains in response speed and accuracy associated with informative memory cues. In Study 2, auditory context facilitated speeded target detection 24 hours after learning just as well as 1 hour after learning. Differences between electrophysiological (EEG) responses associated with informative and uninformative audio-clip cues point to memory rather than attention mechanisms. In Study 3, differences in cognitive performance in carriers of APOE4 at a pre-clinical phase were observed. Notably, while memory recall was unaffected by genotype, APOE4 dose impaired memory-guided attention. A relationship between explicit memory and memory-guided attention was only observed in non-carriers, and this relationship was broken in APOE4 heterozygotes and homozygotes, indicating that APOE4 carriers rely less on explicit memory to facilitate attention. Because memory-guided attention declined with age in APOE4 carriers, it may be an early disease-related impairment rather than a life-long impairment.
Annotating Human Interactome to Predict Pathways and Systematically Analyzing Network Rewiring in Cancer across Multiple Tissues
Keywords: biological networks analysis
computational and integrative biology
data integration
high-throuput data analysis
molecular pathways
protein-protein interactions

Human protein-protein interaction (PPI) networks are essential in regulating most cellular processes and their disruption can cause complex diseases such as cancer. Currently, hundreds of thousands of binary PPIs comprise human interactome, but they lack annotations about tissue- or disease-specificity. Pathway databases provide more detail about these conditions, but they cover only fraction of the proteome. The main goal of this dissertation was to annotate interactome through integrative computational methods and use these annotations, to predict novel protein-pathway associations (Chapter 2), and perform system-level analysis of interactome in cancer (Chapter 3). Chapter 2 describes integration of 4,968 pathways from twenty curated pathway databases. Analysis of these data highlighted several challenges including low proteome coverage (63%), low overlap across different databases, unavailability of direct information about underlying physical connectivity of pathway members, and high fraction of protein-coding genes without any pathway annotations, i.e., 'pathway orphans'. To address these challenges, I integrated these data with PPIs to predict biologically relevant protein-pathway associations. Cross-validation determined 71% recovery rate of our predictions. Data integration and predictions increase coverage of pathway annotations for proteins to 91% and provide novel annotations for 5,402 pathway orphans. These data are publicly available in pathDIP (http://ophid.utoronto.ca/pathDIP). Chapter 3 describes curation of gene expression data of 3,127 primary cancer and normal samples across sixteen tissues and thirty-five cancer types. I used pairwise gene coexpression and differential coexpression to annotate 276,552 PPIs with tissue- and cancer-specificity. Pan-cancer comparison of annotated PPIs provides novel insights toward dynamics of PPI networks in tissue-cancers. We found that while PPI network hubs are present in most of the tissues and cancers, their interactions are highly tissue-cancer-specific. Comprehensive graph theory-based analysis shows that highly dense network modules (e.g., protein complexes) are frequently maintained in both normal and cancer, but they are wired differently. I demonstrate on two examples of the potential of these annotations in discovering novel cancer genes and drug pathways.
Development of Prognostic Models for Survival and Quality of Life in Surgically Managed Patients with Metastatic Spinal Cord Compression
Keywords: Clinical Prognostic Model
Metastatic Epidural Spinal Cord Compression
Quality of Life
Surgery
Survival

Untreated Metastatic Epidural Spinal Cord Compression (MESCC) leads to irreversible neurologic deficits and worsened quality of life (QoL). While all existing Clinical Prognostic Models (CPMs) predict survival, most were derived from retrospective data from small patient samples using unclear methodology and there is no consensus related to their accuracy. Of note, to date, there is no CPM predicting QoL. Accurate CPMs for survival and QoL may assist clinicians and patients in the process of joint therapeutic decision-making and help patients form realistic expectations related to the outcome of surgery. We conducted a survey and a systematic literature review to isolate key preoperative predictors of survival and QoL. In accordance with The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guideline, we identified significant predictors of survival and performed an external validation of eight existing CPMs for survival. Using high-quality prospective data, we integrated evidence from the current literature, expert opinion and statistical findings to create CPMs of survival and QoL in accordance with the TRIPOD guideline. We identified the site of primary tumor, the presence of organ metastasis and the SF-36 physical component score (PCS) to be significant predictors of survival. For all eight CPMs evaluated, discrimination was possibly helpful and calibration was poor. Our CPM of survival includes five predictors (SF-36 PCS, type of primary tumor, presence of organ metastasis, MESCC treated with radiotherapy prior to surgery and male sex) while the CPM of QoL at 3 months after surgery consist of four predictors (KPS, living in NA, SF-36 PCS and SF36 mental component score). Our CPMs demonstrated possibly helpful discrimination and good calibration. In accordance with the TRIPOD guideline, we created and internally validated a CPM of survival and the first CPM of QoL at 3 months after surgery for patients with MESCC. We believe we have achieved the maximum prognostic ability using traditional predictors, methods and outcome measures. Future work will concentrate on further external validation of CPMs of survival and QoL, to examine other predictors of outcome, such as molecular diagnosis and biomarkers, and to employ disease-specific outcome measurement instruments.
Dynamic Mechanism Design without Transfers
Keywords: Game Theory
Mechanism Design

This thesis consists of three chapters. In chapter 1, titled "Design of Committee Search," I apply a mechanism design approach to committee search problems, such as hiring by a department or a couple's search for a house. A special class of simple dynamic decisions rules have agents submit in each period one of three votes: veto, approve, or recommend; the current option is adopted whenever no agent vetoes and at least one agent recommends. I show that every implementable payoff can be attained by randomizing among these simple rules. This result dramatically simplifies the design problem. In chapter 2, titled "School Choice with Observable Characteristics," I study a school choice problem where students have observable characteristics that are correlated with their preferences. For example, one such characteristic may be the location of a student's home, which is correlated with preferences if students tend to prefer nearby schools. I consider mechanisms that are envy-free, efficient, and treat students with the same observable characteristics equally. I show that the welfare-maximizing mechanism in this class is a modified probabilistic serial mechanism with capacities. These capacities specify the maximum number of students with given characteristics that can be admitted into each school. In chapter 3, titled "Mechanism Design for Stopping Problems with Two Actions," I analyse a class of dynamic mechanism design problems in which a single agent privately observes a time-varying state, chooses a stopping time, and upon stopping, chooses between two actions. The principal designs transfers that depend only on the time the agent stops and on the alternative the agent chooses. The analysis provides necessary and sufficient conditions for implementability in this environment. In particular, I show that any stopping rule in which the agent stops the first time the state falls outside of an interval in the state space can be implemented if and only if a pair of monotonicity conditions is satisfied.
21st-Century Cello Pedagogy: Examining the Efficacy of Online Cello Lessons
Keywords: cello
conference
contemporary
distance
learning
video

The use of video-conferencing software and online platforms has brought many parts of the world closer together and has enabled audiovisual communication with greater ease than ever before. As with other technological developments, there are both advantages and disadvantages associated with video-conferencing and the rapid transmission of information. This dissertation will focus on the use of video-conferenced teaching in applied cello lessons, and will also examine subscription-based websites, in order to ascertain the efficacy of distance instruction in both synchronous (real time) and asynchronous (pre-recorded) contexts. The thesis begins with a consideration of the history of cello pedagogy over hundreds of years, from early print-based method books to the use of communication and recording technologies in the 20th century. To assess the current state of online cello instruction, the thesis includes interviews with online cello instructors and web creators, as well as a review of the author’s experience in video-conferenced lessons and other online platforms. The conclusion outlines what factors are necessary in order for effective cello instruction to take place via an Internet connection.
Vertical Integration of Optical Waveguides in the AlGaAs/GaAs Semiconductors
Keywords: Aluminum gallium arsenide
Monolithic integration
Multi-guide vertical-integration
Nanofabrication
Photonic integrated circuits
Waveguides

The rapidly growing Internet services put a higher bandwidth requirement on datacenters. A lowpower and low-cost photonic integrated circuit (PIC), using wavelength division multiplexing (WDM), holds the promise to further scale the density, reach, and bandwidth needed for nextgeneration datacenter networks. Multi-guide vertical-integration (MGVI) scheme improves device yields, saves substantial fabrication costs and offers many other advantages. The AlxGa1-xAs semiconductors provide optical gain and allow for the monolithic integration of different active and passive components. In this thesis, we demonstrate the vertical integration of optical waveguides via the MGVI scheme in the AlxGa1-xAs semiconductors. First, we begin by developing wet chemical etching techniques and demonstrate sacrificial etching of AlxGa1-xAs layers with a low aluminum content against layers with a high aluminum content. We also demonstrate sacrificial etching of Al0.7Ga0.3As layers against AlxGa1-xAs layers with x
X-ray Spectroscopy and Scattering Studies on Thermoelectric Skutterudites
Keywords: Extended X-ray Absorption Fine Structure
Local structure
Skutterudite materials
thermoelectrics
Vibrational Properties

The interest in developing high performance thermoelectric materials has inspired a wide range of theoretical and experimental studies of their structural, electrical and lattice dynamical properties. In this dissertation, I have employed x-ray spectroscopy and scattering techniques to investigate the local structure and vibrational dynamics of various fillers and dopants in thermoelectric Co4Sb12-based skutterudites. X-ray absorption spectroscopy studies were carried out to elucidate the local structure of Ga and Yb dopants in a series of polycrystalline YbxGayCo4Sb12. EXAFS data at Ga K-edge provide direct experimental evidence that Ga dopants occupy two distinct crystallographic sites. The fraction of Ga occupying the 24g site increases gradually as a function of additional Yb, reaching 100% when x = 0.4. Combined with the Fermi level shift observed in the x-ray absorption near-edge structure (XANES) spectra, we find the charge-compensated defect model can explain the observed increase of Ga24 fraction very well. This study provides an important strategy to optimize the thermoelectric performance in partially filled skutterudites. Significant interaction between filler species was further investigated in the double- filled YbxInyCo4Sb12 samples. We found in both Yb-Ga and Yb-In double-filled skutterudites the local structure of Ga and In are subject to the lling concentration of the secondary filler, Yb. However, contrary to the Ga dopants which form dual-site defects in the absence of Yb fillers, the result shows that both Yb and In occupy the on-center 2a sites exclusively in their single-lled samples. The temperature dependent EXAFS results provide further evidence that the In2a, very similar to the normal filler Yb, is loosely bound inside the cage and vibrates as an Einstein oscillator. This is distinct from Ga2a which forms a stiff bond with the cage atoms at a rather high Debye temperature. The vibrational dynamics of Yb fillers has been studied in YbxCo4Sb12 compounds by performing both EXAFS and inelastic x-ray scattering (IXS) measurements. The low-energy vibrational mode introduced by the Yb fillers has been successfully detected. We further found that the cubic anharmonic interaction between Yb and Sb is well evident at high temperatures.
“The Metropolitan Moment: Municipal Boundaries, Segregation, and Civil Rights Possibilities in the American North”
Keywords: Boston
busing
Detroit
metropolitanism
Philadelphia
suburbs/suburban

Exploring battles over school desegregation in metropolitan Boston, Detroit, and Philadelphia in the 1960s and 1970s, “The Metropolitan Moment” examines how black and white city dwellers at odds over integration within the city pursued – and sometimes allied over – efforts that crossed municipal lines to incorporate the suburbs in desegregation remedies. Though possessing divergent motivations, such as the white tactical aim of ensuring white majorities in all area schools by enlarging the desegregation area and the black desire for improved educational opportunities, both groups sought access to white suburban schools and at times acted together in court in an attempt to implement metropolitan desegregation. The search for such solutions opened a “metropolitan moment” across the urban North in the late 1960s and early 1970s when proposed regional remedies offered real possibilities of heading off white flight, fostering interracial coalitions, and substantively combatting segregation. Though this moment was foreclosed by the U.S. Supreme Court’s 1974 decision in Milliken v. Bradley – a case prompted in part by just such a surprising urban black-white alliance in Detroit – its legacies, including suburban anti-busing movements that helped fuel the rise of the New Right and the transformation of the Democratic Party, and the larger retreat from metropolitan solutions to metropolitan dilemmas of race, schooling, services, and inequality, echo down to today. The findings complicate several historiographies pertaining to the long civil rights movement, post-World War II urban and suburban history, the rise of the right, and representations of the “busing” controversy. Throughout, “The Metropolitan Moment” broadens the conception of the municipal reformer to include both ordinary black parents and white reactionaries.
A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans
Keywords: Alternative splicing
C. elegans
Genetics
Genomics

Alternative splicing (AS) is a key mechanism that contributes to the high level of complexity present within metazoan proteomes. This process is highly regulated and important for the development for any animal. With advances in high-throughput technologies, our knowledge of the many AS events that occur in the cell has rapidly increased. However, for many of these events, it is still not known which splicing factors (SF) are involved, and how they regulate splicing outcomes. Here, I use a genomic approach in the nematode C. elegans to study how SFs govern AS events during development. Specifically, for this thesis, I focus on four SFs – ASD-1, FOX-1, EXC-7 and MEC-8. In the first data chapter, I use RNA sequencing, RNA-binding preferences and conservation information to identify likely direct targets of these SFs. I find that AS regulation by these SFs is often combinatorial and converges upon genes with neuronal and cytoskeletal functions. I further show that loss of these SFs can lead to synergistic defects in the neuromuscular system. Many of these co-regulated AS events are also developmentally regulated, suggesting a crucial role in development. In the second data chapter, I then focus on a subset of MEC-8 targets to provide a more detailed view of splicing regulation. I find that MEC-8 regulates the developmental AS transitions in multiple transcripts encoding components of the fibrous organelle – a complex crucial for maintaining structural integrity in the worm. Differential mec-8 expression during development likely contributes to the dynamic regulation of these AS events in a cell- and developmental-stage specific manner. Finally, I find that these AS patterns can vary among C. elegans natural isolates and differential splicing is associated with differences in mec-8 expression. These data suggest that the study of natural variation in AS regulation can provide insight into the regulation of splicing regulatory pathways.
Student Development of Team-effectiveness Behaviours in Engineering Teams
Keywords: engineering
first year design
online learning
students
team-effectiveness behaviours
teams

The Canadian Engineering Accreditation Board requires all graduating engineering students to demonstrate the ability to work effectively in teams. This thesis provides a response to this requirement through the development and testing of an on-line team-effectiveness learning system (TELS) for use in large 250-900 student classes. Based on Kolb’s Experiential Learning Theory and Hewson and Little’s feedback model, TELS provides students an opportunity to develop their team-member effectiveness through: i) guiding intra-team self and peer assessments of teamwork using an inventory of behaviours customised for engineering students; ii) providing students self and peer feedback to identify opportunities for improvement, and iii) providing online, integrated lessons and exercises on how to improve each behaviour within the system. The Team-Effectiveness Learning System (TELS) was developed and tested in a multi-year study of two first-year engineering design courses. A mixed-methods approach was taken to assess the efficacy of the system, combining an analysis of students’ self and peer assessments, their use of the online learning system and students’ self-reported assessments of the system’s utility. Findings from three-years of testing and revision indicate that TELS guided students to provide feedback for improvement that was reliable and that the behavioural inventory used to provide feedback expanded student discussion of relational and communication behaviours. A statistically significant improvement in students’ self and peer assessed weaknesses was seen between mid-term and end-of-term feedback. Student improvement was predominantly motivated by the feedback a student received; students who received feedback that had a greater focus on strengths and weaknesses reported being more motivated to improve their behaviour and did improve their behaviour more than those whose feedback discussed few strengths and weaknesses. Student improvement methods focused on reviewing their feedback and reflecting on how to improve their weaknesses – only 13% of students used the online lessons as scaffolding to support development. Integration of the Team-Effectiveness Learning System (TELS) into team projects in engineering education affords instructors in large classes a way to provide personalised feedback to individual students. In first-year engineering design classes it has been found to improve students’ team behaviour and expand students’ understanding of effective teamwork.