VictorJuiz/thesis huggingface dataset:
Exogenous Glucagon-like Peptide-2 in Neonatal Piglet Models of Short Bowel Syndrome: Does the Intestinal Adaptive Response Vary with Remnant Intestinal Anatomy?
Keywords: short bowel syndrome
intestinal adaptation
glucagon-like peptide-2

Glucagon-like peptide-2 (GLP-2) augments intestinal adaptation in animal models of short bowel syndrome (SBS) and in adult patients with SBS. However, GLP-2 has not been used as a therapy for pediatric SBS. In this thesis, it is hypothesized that exogenous GLP-2 therapy will improve outcomes of intestinal adaptation in proximal intestinal resection (JI) and distal intestinal resection (JC) neonatal piglet models of SBS. Improvements in morphological parameters (increased small intestinal length) and histological parameters (increased jejunal villus length or jejunal crypt depth) of intestinal adaptation in JI and JC neonatal piglets treated with GLP-2 were observed. However, improved clinical outcomes (fewer days of diarrhea, fewer days on parenteral nutrition, more days on enteral nutrition alone) were only observed in GLP-2 treated JC animals. Since the JC anatomical subtype (no remnant ileum) represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.
Robust Consistency Checking for Modern Filesystems
Keywords: Filesystems
Consistency checking
Reliability
Runtime verification
Declarative
Datalog
Btrfs

A runtime file system checker protects file-system metadata integrity. It checks the consistency of file system update operations before they are committed to disk, thus preventing corrupted updates from reaching the disk. In this thesis, we describe our experiences with building Brunch, a runtime checker for an emerging Linux file system called Btrfs. Btrfs supports many modern file-system features that pose challenges in designing a robust checker. We find that the runtime consistency checks need to be expressed clearly so that they can be reasoned about and implemented reliably, and thus we propose writing the checks declaratively. This approach reduces the complexity of the checks, ensures their independence, and helps identify the correct abstractions in the checker. It also shows how the checker can be designed to handle arbitrary file system corruption. Our results show that runtime consistency checking is still viable for complex, modern file systems.
Functional Interactions between the Discoidin Domain Receptor 1 and Beta 1 Integrins
Keywords: Collagen
Discoidin Domain Receptor 1
Beta 1 Integrins
Remodeling
Glycosylation
Phagocytosis

The rate limiting step of phagocytosis is the binding of collagen to specific receptors, which include β1 integrins and the discoidin domain receptor 1 (DDR1). While these two receptors may interact, the functional nature of these interactions is not defined. We examined the effects of DDR1 over-expression on β1 integrin function and determined that DDR1 over-expression enhanced cell attachment through β1 integrins. These data are consistent with data showing that DDR1 over-expression enhanced cell-surface, but not total, β1 integrin expression and activation. As shown by experiments with endoglycosidase H, DDR1 over-expression increased glycosylation of the β1 integrin subunit. Collectively these data indicate that DDR1 enhances β1 integrin interactions with fibrillar collagen, possibly by affecting the processing and trafficking of β1 integrins to the cell surface. Our data provide insight into the mechanisms by which fibrotic conditions such as cyclosporine A-induced gingival overgrowth are regulated.
Vision-based Augmented Reality for Formal and Informal Science Learning
Keywords: Digital Media
Learning Sciences
Augmented Reality
Museology
Education
Informal Learning
Information Science
Qualitative Methodology

This thesis explores the application of vision-based augmented reality in formal and informal educational environments. It focuses on the common practices, concerns, and priorities that developers and content creators in each environment frequently encounter, offering insights into how these experiences are changing with the incorporation of new digital media technologies and the hardware platforms that support them. The research outlined in this thesis uses qualitative methods, assembled around a series of twelve hour-long interviews with highly-experienced educators, developers, researchers, and designers, and analyzed using a grounded theory approach. This thesis introduces original research about the role of computer vision-based augmented reality as an educational medium, a topical discussion in information studies, museum studies, learning sciences, and a number of other fields, and makes a theoretical commitment to addressing the ways that material and virtual objects come to interact meaningfully in a variety of learning environments.
The LNX Family of Multi-PDZ E3 Ligases: Using a Mutagenesis-based Approach to Establish the Role of PDZ Domains in LNX1 Function
Keywords: Ubiquitin
E3 Ligase
Protein Interactions
Mutagenesis
PDZ Domain
Cell Biology
Biochemistry

LNX1 belongs to a family of multi-PDZ domain containing RING-type E3 ligases. Several interactions have been mapped to its PDZ domains, but the role of each domain in LNX function has not yet been determined. To study individual PDZ domain function in the context of full length protein I generated point mutations in peptide binding sites of each of PDZ domain, and in a putative phosphoinositide binding site of LNX1 PDZ4. Peptide binding was successfully disrupted by an arginine or lysine to alanine mutation in the peptide binding cleft. A LNX1 PDZ4 mutant with lysine residues in a putative phosphoinositide binding site mutated to glutamate displayed decreased membrane localization. The impact of each PDZ mutation on cell morphology and substrate ubiquitination was also investigated. I identified a potential role for PDZ binding in auto-inhibition of RING function. Additionally, novel interactions between LNX1 and Frizzled family members were identified and characterized.
Using Phosphine Aldehydes to Generate New Metal Complexes and the Synthesis of Chiral NHC-amino Ligands
Keywords: inorganic
organometallic
catalysis
ligand
phosphine
NHC
carbene
imidazolium
hydrogenation

Several new late transition metal complexes containing P-O and P-N ligands derived from 2-dicyclohexylphosphinoacetaldehyde were synthesized. A facile one-pot template method is used for the synthesis of P-N complexes, where the phosphine aldehyde and amine can undergo a condensation reaction to form a phosphine-imine metal complex in the presence of a metal precursor. Metal complexes with phosphino-enolate, imine, and oxime ligands are synthesized. Ni(II), Pt(II), Rh(I) and Ir(I) metal centres were investigated. The Rh(I) and Ir(I) complexes contain a 1,5-cyclooctadiene ligand, thus resembling Crabtree’s hydrogenation catalyst [Ir(COD)(py)(PCy3)][PF6]. These complexes are also active catalysts for olefin hydrogenation. Furthermore, the synthesis of a new chiral amine functionalized NHC ligand is explored, which has potential applications as a ligand in the metal-catalyzed enantioselective hydrogenation of polar bonds. This ligand is inspired by previous achiral hydrogenation catalysts reported by Morris et al. that displayed high activity for a variety of unsaturated substrates.
The Role of Moral Emotions in Children's Sharing
Keywords: development
sharing
moral emotions
sympathy

This study examined the development of sharing and its associations with moral emotions in an ethnically diverse sample of 244 4-, 8-, and 12-year-old children. Sharing was measured through participants’ allocation of resources in the dictator game. Participants completed self-report measures of sympathy and anticipated their negatively and positively valenced moral emotions (i.e., guilt and pride) following actions that either violated or upheld moral norms. Results demonstrated an age-related increase in sharing between ages 4 and 8. For children with low levels of sympathy, sharing was predicted by negatively valenced moral emotions following the failure to perform prosocial duties. Sympathy also emerged as a significant predictor of sharing behaviour in early childhood. The implications of these results are discussed in relation to children’s developing norms of fairness and the emergence of two compensatory emotional pathways to altruistic sharing, one via sympathy and one via negatively valenced moral emotions.
Predictors of 25-hydroxyvitamin D Serum Concentrations among Non-western Immigrant Preschool Children
Keywords: Nutrition
Vitamin D
Early childhood
TARGet Kids!

We determined whether children older than 1 year from non-western immigrant families had lower serum 25-hydroxyvitamin D levels than children from western born families. Children ages 1-6 years were recruited through the TARGet Kids! practice based research network. Univariable analysis revealed that non-western immigrant children had 4 nmol/L lower 25-hydroxyvitamin D (p=0.006; 95% CI:1.4-8.0) and increased odds of 25-hydroxyvitamin D <50 nmol/L (OR 1.9, 95% CI:1.3–2.9). After adjustment for known vitamin D determinants, cow’s milk intake, vitamin D supplements, season and age were significant covariates and current vitamin D supplementation had the strongest confounding effect. In order to use the ethnicity variable, we developed a new standardized geographically based closed-ended ethnicity question, which was a practical alternative to the widely used open-ended ethnicity questions. There was an association between non-western immigration and lower 25-hydroxyvitamin D in early childhood and this appears primarily related to known vitamin D determinants.
Mobilities of Aboriginal Youth: Exploring the Impact on Health and Social Support through Photovoice
Keywords: Aboriginal health

Dramatic growth in Canada’s urban Aboriginal population has led to high rates of Aboriginal mobility. Despite much quantitative data, very little is known about the mobility experiences of Aboriginal peoples or its impacts. Furthermore, while mobility may present barriers for shaping social connections important to individual health, research in this area is minimal, especially among Aboriginal youth. Using community-­‐based participatory research (CBPR) the purpose of this thesis is to examine how mobility shapes the social networks and health of Aboriginal youth in the city of Winnipeg, Manitoba. While highlighting the use and valuableness of CBPR methods, the research demonstrates that mobility impacts both the development and maintenance of social relationships among Aboriginal youth as well as influences the types and qualities of these relationships. Additionally, mobility indirectly shapes health through its effect on social support, which was shown to impact health positively and negatively through direct and indirect pathways.
Optimization of Dose Schedules in Radiotherapy
Keywords: Fractionation
Radiotherapy

Purpose: Fractionation in radiotherapy is the scheduled break up of a total treatment dose into individual doses. The goal of this thesis is to seek a mathematically optimal dose schedule, in the context of a biological tissue dose-response model, the linear-quadratic function. Methods: We examined the mathematical properties of the fractionation problem in the context of an arbitrary number of sensitive-structure constraints and determined the properties of the optima. We also implemented a numerical search technique to solve the problem. Results: On the theoretical side, we confirmed and extended the results in the literature. We showed the optima always occur at the intersection of two or more constraints or at the equal dose per fraction point (or at any arbitrary feasible point on the boundary, which includes the two points just mentioned). On the numerical side, we successfully implemented a simulated annealing algorithm to our problem.
Structure-based Development of Vitamin B5 Analogs and Evaluation of their Antimicrobial Efficiency against S. aureus and E. coli
Keywords: Structural biology
N-substituted Pan analogs
Structure-based development
Antimicrobial compounds
Pantothenate

The objective of this study is to evaluate pseudo-substrates of pantothenate kinase (PanK) for the therapeutic treatment of multidrug resistant bacterial infections of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Pantothenate (Pan) analogs, including N- pentylpantothenamide (N5-Pan) and N-heptylpantothenamide (N7-Pan), hamper bacterial growth by utilizing the PanK enzymes, which normally catalyze the rate determining step of the Coenzyme A biosynthetic pathway. Here we report the structures of SaPanK, Human PanK3 and EcPanK complexed with N7-Pan or N5-Pan, all of which have provided the opportunity to investigate the structural differences of bacterial and human Pan binding sites. The MTT assay showed these analogs to exhibit no apparent cytotoxicity against Human A549 lung adenocarcinoma cells, human HepG2 hepatoma cells and human umbilical vein endothelial cells (HUVEC). The presented structural differences have the potential for aiding the development of species-specific antimicrobial compounds with minimal effects on human cells.
Interaction of Hsp104 with Hsp70: Insight into the Mechanism of Protein Disaggregation
Keywords: Hsp104
Molecular Chaperones
Heat Shock Protein
Hsp70

Hsp104 and ClpB are hexameric ATPases that resolubilize aggregated proteins in collaboration with the Hsp70 chaperone system. Hsp104/ClpB functionally interact only with their respective Hsp70 system and this specificity is mapped to the Hsp104/ClpB coiled-coil domain (CCD). We hypothesize that the interaction between Hsp70 and Hsp104/ClpB CCD stimulates nucleotide exchange and release of substrate from Hsp70. In the current study, the CCDs of E. coli ClpB and S. cerevisiae Hsp104 have been purified. Isolated domains are monomeric and well folded. They inhibit refolding of aggregated firefly luciferase in a species-specific manner. We found that the ATPase activity of E. coli DnaK is stimulated at low concentrations of the E. coli ClpB CCD but not by yeast Hsp104 CCD. However, in another bacterial system (Thermus thermophilus) we found that the ClpB CCD inhibits The ATPase activity of DnaK suggesting that the interaction may have different consequences in distinct chaperone networks.
Examination of the Association between Voluntary Accreditation and Resident Safety in Ontario Long Term Care Homes
Keywords: accreditation
long term care
patient safety
rurality
chain membership
ownership
falls
quality of care
quality improvement

Objective: determine whether accreditation through Accreditation Canada is associated with more favorable resident safety in Ontario LTC homes and which facility characteristics are predictive of accreditation. Methods: logistic regression was used to determine predictors of accreditation. To examine the association between accreditation and safety, safety was operationalized as five MDS-RAI quality indicators: prevalence of falls, restraints, catheters, pressure ulcers, and infections. Separate multivariable models were developed for each indicator. Results: the odds of accreditation were approximately six times smaller for municipal (p < 0.001) and non-profit facilities (p < 0.001) relative to for-profits; three times greater for chains relative to non-chains (p < 0.001); and twice as large for urban relative to rural facilities (p = 0.04). Of the five quality indicators examined, only one (falls) was associated with accreditation. After adjusting for confounders, accredited homes were estimated to have 8% lower fall rates than non-accredited homes (p = 0.01).
Platelet Activating Factors and Depressive Symptoms in Coronary Artery Disease Patients
Keywords: depression
coronary artery disease
platelet activating factors
lipidomics

Depression is highly prevalent in coronary artery disease (CAD) and confers an increased risk of morbidity and mortality, yet mechanisms are unknown. Platelet activating factor (PAF) lipids are associated not only with CAD but also with inflammation, oxidative/nitrosative stress, vascular endothelial dysfunction and platelet reactivity which are proposed etiopathological mechanisms for depression. This study investigated the relationship between PAF species and depressive symptoms in 20 CAD patients. Plasma analyses were performed using electrospray ionization mass spectrometry (precursor ion scan). Primary analysis revealed no association between the potent pro-inflammatory PAF PC(O-16:0/2:0) and depressive symptoms measured by the Hamilton Depression Rating Scale [HAM-D] (F=0.405, p=0.533) or Beck Depression Inventory [BDI]-II (F=0.120, p=0.733) in a linear regression. Exploratory analyses revealed potential associations between greater PC(O-18:1/0:0) and greater HAM-D score and greater PC(O-22:6/2:0) concentrations with a greater BDI-II score. This study suggests that specific PAFs might be biomarkers for depressive symptoms in CAD patients.
Performance-based Design of RC Coupled Wall High-rise Buildings with Viscoelastic Coupling Dampers
Keywords: Seismic Engineering
Supplemental Damping
High-Rise Design
Viscoelastic Coupling Damper

A new damping technology, the Viscoelastic Coupling Damper (VCD), has been developed at the University of Toronto for reinforced concrete (RC) coupled wall high-rise buildings. These dampers are introduced in place of coupling beams to provide distributed supplemental damping in all lateral modes of vibration. This thesis presents an analytical investigation of the application of VCDs in a high-rise case study building located in a region of high seismicity. A parametric study has been conducted to determine the optimal number and placement of the dampers to achieve enhanced seismic performance without compromising the wind response of the structure. Nonlinear time history analyses have been carried out in order to compare the seismic performance of a conventional coupled wall building to alternative designs incorporating VCDs. Results highlight the improved performance of VCDs over RC coupling beams at all levels of seismic hazard. A design procedure for seismic-critical buildings is proposed.
An In silico Investigation of the Metabolic Capabilities of Anaeromyxobacter Dehalogenans and Field-scale Applications
Keywords: Environmental Engineering
Microbial Models
Optimization
Genome Sequences
Metabolism
Parameter Fitting

In recent years, uranium pollution in the environment has been recognized as a serious threat, and novel in situ microbial bioremediation strategies have been incorporated into field-scale contaminated sites. The Oak Ridge Integrated Field-scale Subsurface Research Challenge (IFC) site is one of the largest uranium contaminated areas in the United States, and a literature review has revealed the potential of uranium reduction by dominant Anaeromyxobacter dehalogenans species that respire during bioremediation. A genome-scale model of A. dehalogenans, a unique microbe with diverse metabolic capabilities that thrives in the natural environment, has been developed, and applied to an in silico field-scale computational setting for evaluation of the biotic uranium reduction in the Oak Ridge IFC site. The metabolic model of A. dehalogenans was integrated into an expanded microbial community framework for the prediction of chemical profiles, and subsequent scenario evaluation of in situ measured data.
Automated Debugging Framework for High-level Synthesis
Keywords: Debug
High-level Synthesis

This thesis proposes a automated test case generation technique for the aim of verifying/debugging High-level synthesis (HLS) tools. The work in this thesis builds a framework that automatically generates random programs with user specified features. These programs are used to verify the correctness of the compiled hardware by comparing the hardware simulation results with the software execution results. This way, users can have a large number of benchmarks to test their algorithms for HLS without having to manually develop test programs. The tool also provides additional ways of analyzing performance of HLS tools. Rather than being a replacement, this technique should serve as a useful complement to existing manually constructed test suites. Together, they can provide more comprehensive verification and analysis for HLS tools.
Effects of Biophysical Parameters in Radiosensitizing Prostate Tumours with Ultrasound-stimulated Microbubbles
Keywords: Ultrasound
Microbubbles
Radiosensitization
Prostate Cancer

We demonstrate here that ultrasound-stimulated microbubbles can lead to enhanced cell death within tumors when combined with radiation. The aim of this study was to investigate different ultrasound parameters in conjunction with different concentrations of microbubbles with regards to this effect. Prostate xenograft tumors in Severe Combined Immunodeficient mice were subjected to ultrasound treatment that involved various peak negative pressures (250 kPa, 570 kPa, and 750 kPa), microbubble concentrations (8 µL/kg, 80 µL/kg, and 1000 µL/kg), and different radiation doses (0 Gy, 2 Gy, and 8 Gy). Twenty-four hours after treatment, tumors were excised and assessed for cell death. Histological analyses demonstrated that increases in radiation dose, microbubble concentration, and ultrasound pressure promoted apoptotic cell death and cellular disruption within tumors. Comparable increases in ceramide, a cell death mediator, were identified using immunohistochemistry. We also demonstrate that clinically-utilized microbubble concentrations combined with ultrasound can induce an enhancement in cell death.
Expanding the Role of Electron Cryomicroscopy in Structural Analysis of Asymmetrical Protein Complexes
Keywords: Structural Biology
V-ATPase
Cryo-EM
Protein Purification

Single particle electron cryomicroscopy (cryo-EM) is a rapidly developing structural biology technique for the study of macromolecular protein complexes. Presently, cryo-EM fills an important niche by facilitating acquisition of 3-D structures of protein complexes not amenable to structure determination by other techniques. Expansion of cryo-EM beyond this niche requires continued improvement in the types of specimens that can be studied as well as the final resolutions achieved. Two studies were undertaken to address these issues. The first examined resolution limitations by quantifying the effect of beam-induced motion in images of beam-sensitive paraffin crystals. The second explored the possibility of using cryo-EM to study the interaction of small effector proteins with a large multi-protein complex, V-ATPase. The results of these studies exposed the fact that fundamental aspects of the imaging and specimen preparation processes remain poorly understood and must be addressed to facilitate future improvements in cryo-EM structure determination.
Mechanisms Underlying Exercise-induced Atrial Fibrillation
Keywords: atrial fibrillation
athletes
exercise

Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia that can present without cardiovascular disease (lone AF). Frequent high-intensity endurance exercise is a risk factor for lone AF, and the pathophysiology of AF induced by intense endurance exercise is unknown. We found that after 6 weeks of intense swimming and running, mice were far more susceptible to AF, but not ventricular arrhythmias. Exercise induced atrial fibrosis, inflammation and slowed conduction without detectible changes in ventricles. Since AF is associated with stretch and since a tumor necrosis factor-α (TNFα) is a mechanosensitive inflammatory factor, mice were treated with the TNFα inhibitor etanercept. Etanercept treatment blocked inflammation, fibrosis, and AF vulnerability in the exercised mice. Consistent with these findings, we found that exercise caused large elevations in atrial pressures. Our findings support the conclusion that mechanical loading of atria during exercise induces TNFα release, leading to structural remodeling and enhanced AF vulnerability.