VictorJuiz/thesis huggingface dataset:
Impacts of aboveground and belowground interactions on the performance of an invasive thistle, Cirsium arvense

Interactions with natural enemies are important to the success of invasive plants in their invaded range. However, little is known of the relative impacts of above- and belowground interactions, or how these interactions may change across the invaded range or between growing seasons. My research investigated these questions using Asteraceae occurring in Ontario, Canada. First, I quantified aboveground herbivory for exotic and native Asteraceae across a latitudinal gradient with the expectation that marginal or more northern populations would experience reduced enemy pressure. Herbivory did not always decline with increasing latitude, but often depended upon the causal herbivorous organism(s) or whether the species was native or exotic. I then further investigated a single non-native species exhibiting strong latitudinal trends in herbivory, Canada thistle (Cirsium arvense). I manipulated distance between plots of C. arvense to see if local spatial and/or temporal isolation also allowed escape from aboveground enemy pressure. Herbivory patterns changed significantly over 4 years, with initial patterns of reduced damage with isolation disappearing by the final year. However, variation in aboveground damage did not explain performance. I then investigated the effects of belowground interactions using a soil feedback experiment with soil collected from across the invaded range, and found C. arvense performed best in range edge soils with shorter invasion histories. This was reflected in compositional shifts in soil mesofauna, and most strikingly, the soil microbiota. Finally, to determine the relative importance of these interactions, I created replicate common gardens in which C. arvense was treated with above- and/or belowground exclosures. Regardless of garden location within the invaded range, protection from both aboveground and belowground enemies improved performance, but belowground interactions tended to have a greater negative impact. Together these results emphasize the importance of spatial and temporal scale in studies of invasions, as well as the need to consider both aboveground and belowground interactions when describing invader performance.

Advisor: Kotanen, Peter M
Ontology-based Context in Visualizations to Facilitate Sensemaking: Case Studies of Phenotype Comparisons

Visualization can help domain experts make sense of their data, but determining appropriate visual representations can be challenging because interpretation relies on tacit domain knowledge. Terminological ontologies explicitly formalize domain knowledge as concepts, entities, and relations that can be represented as a directed-acyclic graph (DAG). This DAG topology could aid sensemaking by visualizing data in the context of domain knowledge. Ontologies were developed to support computational analyses and their application to visualize ontology-annotated data for sensemaking has not been systematically explored. Ontologies define complex relationships between entities and the resulting DAG topology must be simplified to visually represent data. Since the relationships encode domain semantics, they could be leveraged to directly address analysis goals through visualizations that support comparisons and interpretation of patterns and trends. This work contributes Ontology-based Analytical Abstraction for Visualization (OAAV), an approach that uses a DAG representation to fuse ontology-annotated data with the relationships defined by a terminological ontology. OAAV supports existing ontology-based computational analyses, while also enabling transformations into a variety of structured representations for visualization (e.g., hierarchies, matrices, scatterplots, charts). OAAV contributes methods to unify disparate data observations (e.g., quantitative, non-quantifiable, timeseries), to simplify the DAG topology (e.g., breadth, depth), and to compute measures for analysis on data observations (e.g., similarity, relevance). These approaches were developed and refined through three case studies with medical domain experts studying phenotypes in genetic diseases. Resulting prototypes demonstrated that visualizations created with OAAV aligned with the mental models of domain experts, and helped them to perform visual comparisons and interpret patterns and trends. The prototypes developed using OAAV have helped medical domain experts characterize disease subtypes, identify anomalies in their data, and suggest terminological ontology improvements. The prototypes continue to be used by the domain experts, and one has contributed to a scientific publication in the medical domain. OAAV was designed based on a systematic exploration of applying ontology relationships to organize and encode ontology-annotated data for visualization in the biomedical domain. This unified approach could be applied to ontology-annotated data in other domains.

Keywords: Analytical Abstraction
Case Study
Collaborative Design
Hierarchy Comparison
Human Phenotype Ontology
Visualization
Advisor: Wigdor, Daniel J
Chevalier, Fanny
On the Generation of Rapid Eye Movement Sleep and the Reversal of Sleep-Related Hypotonia in Muscles of the Upper Airway

Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. One of the major consequences of REM sleep is an augmentation of the muscle hypotonia that occurs throughout sleep. Hypotonia in muscles of the upper airway is a precipitating cause of obstructive sleep apnea (OSA): a prevalent syndrome characterized by repeated episodes of upper airway narrowing and closure that occur only during sleep. The studies described in this thesis aimed to: (i) identify the role of cholinergic input to the pontine subcoeruleus (SubC) region in the generation of REM sleep, (ii) determine the involvement of the ventrolateral periaqueductal gray (vlPAG) and deep mesencephalic reticular nucleus (DpMe) in the bistability of sleep, and (iii) identify pharmacological targets for the reactivation of the upper airway musculature throughout sleep. The data reported here will show that contrary to the prevailing hypothesis of cholinergic involvement in REM sleep, cholinergic input to the SubC does not induce transitioning into REM sleep but rather reinforces transitions after their initiation, making them quicker and less likely to fail. In a separate study, evidence is presented indicating that vlPAG/DpMe neurons, namely the REM sleep-inactive subpopulation, are not critical regulators of non-REM (NREM)-to-REM sleep transitioning. In contrast, the results of vlPAG/DpMe inactivation instead support a major involvement of REM sleep-active neurons in preventing breakdowns in sleep bistability specifically during REM sleep. Lastly, proof-of-principle is established that targeted blockade of certain potassium channels at the hypoglossal motor pool is an effective strategy for reversing upper airway hypotonia and causing sustained reactivation of upper airway muscles throughout NREM and REM sleep. These findings identify an important new direction for translational approaches to the pharmacological treatment of OSA.

Keywords: acetylcholine
in-vivo
microdialysis
Pons
REM sleep
sleep apnea
Advisor: Horner, Richard L
THE ROLE OF KAT7-DEPENDENT INTRAGENIC HISTONE ACETYLATION ON ENDOTHELIAL CELL GENE REGULATION

Cellular identity is largely defined by a cell’s gene expression profile. Epigenetic mechanisms figure prominently in establishing endothelial cell (EC) gene expression profiles. Although their functional importance in EC-enriched gene regulation has been well characterized at their promoters, their role at the intragenic regions is not clear. Moreover, little is known of the epigenetic modifiers that are critical for EC gene expression. Here, we determined the histone acetylation profiles of select EC-enriched genes and identified a histone acetyltransferase (HAT) that establish these profiles. Specifically, we characterized the histone H3 and H4 acetylation profiles of 19 genes with EC-enriched expression via loci-wide chromatin immunoprecipitation followed by ultra high resolution (5 bp) tiling array analysis in ECs versus non-ECs throughout their genomic loci. Aside from observing differential EC enrichment of H3 and H4 acetylation at the most EC-enriched gene promoters, broad differential intragenic histone acetylation enrichment was surprisingly observed at select EC genes, especially VEGFR-1 and VEGFR-2. Importantly, VEGFR-2 and VEGFR-1 were upregulated in non-ECs by histone deacetylase inhibition. To determine the role of broad intragenic histone acetylation in determining the EC phenotype, we characterized the histone acetyltransferase KAT7. KAT7 was expressed ubiquitously and its protein level decreased in ECs subjected to fluid shear stress. Fluid shear stress may reduce KAT7 expression to promote an anti-inflammatory and vasodilatory state in ECs. Upon depleting KAT7 in human ECs, VEGFR-2 expression was reduced and their angiogenic potential was perturbed. Furthermore, microarray analysis of human KAT7-depleted ECs identified 279 differentially regulated genes (fold change ≥ 2, p ≤ 0.05), many of which are key for growth and angiogenesis. KAT7 depletion in zebrafish embryos disrupted vessel formation and caused loss of circulatory integrity, especially hemorrhage, all of which were rescued with human KAT7. Notably, EC-enriched gene expression, especially VEGFR-1 and VEGFR-2 homologs, was perturbed in these zebrafish embryos. Mechanistically, KAT7 localized to the human VEGFR-2 genomic locus and participated in its transcription by mediating Pol II binding, H3K14, and H4 acetylation in its intragenic region. Collectively, our findings reveal a previously uncharacteried role of intragenic histone acetylation and KAT7 in regulating EC gene expression and function.

Keywords: Chromatin
Endothelial Cells
Epigenetics
Intragenic Histone Acetylation
KAT7
Vascular Biology
Advisor: Marsden, Philip A
Investigating the Role of EphrinB1 in the Control of Xenopus laevis Gastrulation

During animal development, the early embryo undergoes gastrulation to bring the primary germ layers into their definitive positions. The ancestral mode of vertebrate gastrulation can be studied using the African clawed frog Xenopus laevis. A core function of gastrulation is the movement of prospective endoderm from the surface to the embryo interior. In X. laevis, endoderm internalization is achieved through vegetal rotation, a tissue morphogenetic process that has only been characterized at the tissue level. I have investigated the cell and molecular basis of endoderm morphogenesis in X. laevis gastrulae to connect vegetal rotation with common mechanisms of germ layer internalization in other organisms. I characterized the arrangement, shape change, and migration of cells in the endoderm, and found that movement of vegetal endoderm cells located deep to the embryo surface represents an adaptation of mechanisms of monolayer internalization (namely, invagination and cell ingression) to the multilayer structure of the vegetal cell mass. Thus, this movement was termed “deep cell ingression”. Deep cell ingression integrates an amoeboid-type motility whereby cells propel themselves forward using strategic cell shape changes to move, but with different rates, a unique mode of intercellular migration where cells move with a common direction but at different velocities with respect to neighbouring cells to drive cell rearrangement during vegetal rotation. Despite their collective movement, endoderm cells are separated by a vast network of extracellular material. Cells are interconnected by stitch-like contacts, and cell migration requires the adhesion molecule C-cadherin, and the matrix protein fibronectin. A basic requirement for migration is that cells must detach to complete rearrangement, and in this regard, the leading cell resolves its contact with the following cell through trailing edge retraction involving ephrinB1-dependent macropinocytosis and trans-endocytosis. Beyond the endoderm, ephrinB1 is also required for the modulation of ecto- and mesoderm tissue cohesion.

Keywords: Cadherin
Collective migration
EphrinB1
Fibronectin
Gastrulation
Xenopus
Advisor: Winklbauer, Rudolf
Exploring the Extent of Interactions in Activity-Based Models: A Critical Examination of Intra-Household and Spatial Interactions Through Choice Modelling

This research increases the overall understanding of a subset of interactions that influence patterns of behaviour: intra-household interactions and spatial interactions. Understanding these interactions and their influence on travel behaviour is essential to developing policy sensitive models. These models provide much of the prerequisite information for evidence based planning. This understanding is framed through a review of existing best practices in travel demand modelling and a discussion of how independent models can be integrated within a larger framework. The thesis presents four empirical models that incorporate either one or both interactions. A model of joint household mode choice which incorporates decisions regarding joint travel and vehicle allocation is estimated. To accomplish this, the model uses a novel choice set formation technique. This is the first modelling to accomplish these tasks simultaneously. Models of transit station location choice are estimated using a newly proposed model structure, the spatially weighted error correlation model. These spatial models are used to compare the difference between independent (transit accessed by driving alone) and joint (transit accessed by being dropped off) spatial choices. The presented model outperforms existing models used to capture the same trend and provides new behavioural insights. A model of chauffeur allocation and location choice for daycare trips is estimated. This model incorporates spatial constraints in this decision through the application of a stochastic frontier model to generate task allocation specific spatial choice sets. This allows for a reduction in the sampling frame for spatial choices. Finally, a model of high school escort and household mode choice is estimated using a parallel constrained choice logit formulation. This empirical investigation generalizes the parallel constrained choice logit to allow for any number of household members to be considered. Concurrently, this empirical analysis highlights a flaw within an existing “best practice” modelling framework.

Keywords: Choice Modelling
Intrahousehold Interactions
Spatial Interactions
Travel Behaviour
Travel Demand
Advisor: Nurul Habib, Khandker M
Effects of Cranial Irradiation on Adult Hippocampal Neuronal Development and the Role of p53

Cranial radiotherapy is a standard treatment for brain tumours, but is associated with late side effects including compromised cognitive functions that can significantly impair patients’ quality of life. Cognitive impairment is a major dose-limiting factor for cranial radiotherapy, and has therefore been an important subject of study. A large body of preclinical studies suggest that injury to the hippocampus, a key structure for learning and memory, contributes to radiation-induced cognitive impairment. Hippocampus houses the life-long generation of new neurons, a process termed neurogenesis. Neurogenesis inhibition is considered to be one of the most important mechanisms leading to post-irradiation cognitive impairment. Mechanistic insights into how radiation affects neurogenesis could therefore help to alleviate the undesirable effects from cranial radiotherapy. I postulate that p53, an extensively studied tumor suppressor known to play an important role in both radiation biology and stem cell biology, regulates post-irradiation neurogenesis. The role of p53 in post-irradiation hippocampal neurogenesis was examined using transgenic mice with different copy numbers of the p53 gene. We also examined the effects of aging on post-irradiation hippocampal neurogenesis because of the reported age-dependent increase of p53 in the hippocampus. The impact of cranial irradiation on hippocampus was further evaluated using a set of endpoints characterizing cellular senescence to complement limitations associated with neurogenesis endpoints. We showed for the first time that p53 deficiency exacerbated the disruption of hippocampal neuronal development after irradiation in adult mouse brain (Chapter 3). This profound post-irradiation neurogenesis inhibition was associated with increased neural stem cell activation and the depletion of neuronal stem cell pool. Although p53 has been shown to increase with aging in the hippocampus, cranial irradiation was found to further inhibit the age-dependent decrease in hippocampal neurogenesis (Chapter 4). Cranial irradiation resulted in increased expression of senescence markers in mouse dentate gyrus (Chapter 5). Ablation of p53 may alter radiation-induced cellular senescence in the hippocampus, although further investigations are needed to determine the functional significance of this finding. These investigations provide mechanistic insight into the effects of cranial irradiation on hippocampal neuronal development and the pathophysiology of cognitive impairment after cranial irradiation.

Keywords: aging
cranial radiation
neurogenesis
neuroinflammation
p53
senescence
Advisor: Wong, C. Shun
Low power high speed optical links in CMOS

This thesis presents dierent methods for power ecient implementation of optical receivers in CMOS. The major sources of power consumption in short reach optical links are the transimpedance amplier, and the gain stages in the receiver and the laser biasing and equalization in the transmitter. To reduce the power in the receiver this thesis proposes methods that utilize the fast switching properties of Advanced CMOS technologies and avoid the power hungry gain ampliers less suited to CMOS. It has been shown that the proposed methods can also improve the sensitivity of the receiver which in turn reduces the demand on the very strong drive of the laser in the transmitter. On the transmitter side a new type of the equalizer is proposed which allows for lowering the laser bias and compensating for resulting poor transient response in the electrical domain. The low power implementation of the equalizer also helped to reduce the link lower further more.

Keywords: CMOS
equalizer
Optical
receiver
transmitter
VCSEL
Advisor: Chan Carusone, Anthony
Characterizing the Nuclear Function of the Cell Adhesion Molecule Fat and Chromatin Regulation by the Inner Nuclear Membrane Protein Speg

Tissue growth, pattern formation and cell metabolism are fundamental to animal development. Coordination of these aspects requires elegant signal transduction systems. In Drosophila, fat (ft) encodes an enormous atypical cadherin that is important for such coordination. Ft functions at the cell surface, regulating tissue growth through the Hippo pathway and Planar Cell Polarity (PCP) tissue patterning. Ft also enters mitochondria to regulate mitochondrial function and metabolic state. However, the coordination of Ft’s functions remains largely unknown. In the first part of my thesis, I present surprising results suggesting that Ft can be cleaved to release an intracellular fragment, which translocates into the nucleus. In the nucleus, Ft is associated with chromatin. Using DamID-microarray, a DNA binding site mapping technique, I showed that Ft binds to specific genomic loci in vivo. Through ChIP-seq, I characterized the genome-wide DNA binding profile of Ft in vivo. ChIP-seq results suggested that nuclear Ft binds mostly open chromatin. Interestingly, the ChIP-seq profile of Ft is highly correlated with that of the Hippo pathway transcription cofactor Yki. Overall, I propose that nuclear translocation of Ft is a novel mechanism by which Ft exerts function. In the second part of my thesis, I focused on Speg, an inner nuclear membrane protein essential for germ cell development. Although the nuclear envelope and lamina have been implicated in chromosome organization and gene regulation, the role of Speg is unknown. Using DamID, I found that Speg is specifically associated with repressive chromatin in vitro and the Speg-associated genes are clustered. Using ATAC-seq chromatin accessibility assay and mRNA-seq in vivo, I found that chromatin accessibility is affected and some affected regions correlate with gene expression changes in speg mutants. Overall, I propose that speg is important for the regulation of chromosome organization and gene transcription.

Keywords: DamID
Fat
nuclear envelope
nucleus
Speg (CG9723)
the Hippo pathway
Advisor: McNeill, Helen
The Role of Visual Representations in a Knowledge Community and Inquiry Curriculum

This design-based research study describes the design, implementation, and evaluation of a suite of technology applications, curriculum materials, and activities, created to support a learning community to collectively investigate a digital ecosystem simulation called WallCology. The specific research goal is to understand the role of visual representations within student and teacher practices, including their use of digital technologies and paper-based activities. Curriculum designs were intended to support small groups of students in their progression through an inquiry script, within the broader context of the whole community. The theoretical construct that guided the creation of this script, and all associated tools and materials, was the Knowledge Community and Inquiry model, in which a collective inquiry curriculum is indexed to specific learning goals, to ensure that the learning community makes directed progress towards these goals. The analysis of this Wallcology community has two parts. The first analysis uses an innovative visual timeline methodology to understand the participant structures, activity types, and roles associated with activities involving visual representations. Findings show that visual representations were used in several distinct participant structures: individual, small group, whole-class discussion, and teacher-guided construction. Visual representations played a role in four distinct activity types: foundational work, contributing to the digital knowledge base, problem solving, and verbal knowledge sharing. Finally, visual representations played a wide range of logistical, pedagogical and conceptual roles within the curriculum, serving as attentional beacons, facilitating connections, providing exemplars and templates, organizing group knowledge, and scaffolding activities. The second analysis evaluates how students engaged in scientific explanations within presentations that were made during the Investigation phase of the unit, with a focus on the role of visual representations during each component of their explanation. Students used visual representations fluently within their scientific discourse. This thesis closes with recommendations for future designers of classroom inquiry experiences.

Keywords: Curriculum design
Educational technology
Elementary science
Knowledge building
Visual representations
Advisor: Slotta, James D.