VictorJuiz/thesis huggingface dataset:
Oestrogen Receptor-alpha Regulates Non-canonical Hedgehog-signalling in the Mammary Gland
Keywords: estrogen receptor
hedgehog
mammary gland
mouse model

Mesenchymal dysplasia (mes) mice harbour a truncation in the C-terminal region of the Hedgehog (Hh)-ligand receptor, Patched-1 (Ptch1) and display a block to mammary ductal elongation at puberty. Our lab previously demonstrated that epithelial cell-directed expression of activated c-src rescued this block to mammary development and induced estrogen receptor-alpha (ER) expression. Using a genetic approach where a conditional allele of ER was expressed on the mes background, we demonstrated that restricted expression of ER also rescues mes mammary morphogenesis with similar kinetics as the MMTV-c-srcAct mice. We further demonstrated distinct cell-type specific canonical Hh signalling in primary mammary epithelial and mesenchymal cells, and identified a novel Erk1/2 activating Hh signalling system that requires the activities of c-src and ER, but not Smoothened (smo). These data reveal a novel Hh-signalling cascade operating through c-src and ER that is required for mammary gland morphogenesis at puberty.
A Population-based Analysis of the Clinical Course of Colonic Diverticulitis and its Evolving Management
Keywords: Colectomy
Diverticular disease
Diverticulitis
Epidemiology
Surgery

Evidence has accrued to support change in the management of colonic diverticulitis. Advances in imaging and medical management suggest more patients may be managed non-operatively; while various new operative approaches have been proposed as an alternative to Hartmann's procedure when urgent surgery is necessary. Furthermore, published reports suggest the clinical course of the disease may be characteristically benign; suggesting interval elective colectomy may be unnecessary for the majority of patients, even those with known risk factors. Reports to date consist predominantly of institutional cohort studies with high loss to follow-up and failure to account for competing risks. To address the gaps in knowledge, we performed a population-based retrospective cohort study. The objectives of this study were to (a) evaluate temporal trends in the management of diverticulitis, and (b) characterize the clinical course of the disease following initial non-operative management. Results from this study will help to inform best practice recommendations.
Community Diversity and Functional Capabilities of Benzene­‐Degrading Enrichment Cultures
Keywords: Benzene
Bioremediation
Community diversity
Metagenomics

Benzene is prevalent, toxic, and persistent in anaerobic environments. Anaerobic benzene degradation has been proven, but is not well understood. The goals of this research were to determine the community composition of anaerobic nitrate-reducing benzene-degrading enrichments and propose likely metabolic roles of organisms present. Highly diverse communities were present in the enrichments, with multiple organisms capable of carrying out similar roles. A metagenome assembly was generated from a nitrate-reducing, benzene- degrading enrichment culture. Further evidence for fermenting Peptococcaceae as the initiator of benzene degradation was established. The potential for benzene degradation to be linked to other terminal electron acceptors (i.e., CO2) was confirmed, further supporting that the initial benzene degradation steps are carried out in a fermenting syntroph. An understanding of the functions of different organisms can inform culturing techniques to increase culture growth and benzene degradation rates. Genes present in the metagenome could be used as biomarkers for benzene degradation.
Evaluation and Visualization of Multi-level Contingencies in Power Systems
Keywords: Contingency
Continuation Power Flow
Power System
Tree
Treemap
Visualization

Contingency analysis is a critical technique for evaluating the operational capability of power systems and characterizing their vulnerability to component faults. The traditional requirement for reliable operations has been an n-1 security constraint --- an electrical network should be resilient to contingencies involving any one element.Contingency analysis is critical to evaluating the operational capacity of power systems and characterizing their vulnerability to component faults. As we look to increase the resilience of networks to element failure, the instance of multiple contingencies is of growing concern for planners and operators in identifying weak points in the system. Multi-element contingencies introduce new challenges for how to reliably and consistently measure the severity of a fault, how to perform contingency analysis on an expanding range of contingency scenarios in a timely manner, and how to interpret the increasingly hierarchical data obtained by contingency analysis. This research explores techniques that can be used to generate, summarize and display the results of multi-element contingency analyses in power systems, including high-performance computational methods for evaluating contingencies and new visualization techniques that leverage visual summarization and live interaction to extract valuable insights from the resulting data.
Synchronization Control of Interconnected Systems with Applications to Neuronal Models
Keywords: Input Output Approach
Parkinson's Disease
Synchronization Control

This thesis investigates the control of synchronization for a general class of compartmental models. The system consists of interconnected compartments. Each compartment is an interconnection of subsystems called species, which are modeled as input-output operators in the extended L_2 space. Compartmental models are ubiquitous in biological networks modeling. The distinctive feature of this thesis is the presence of an external feedback loop that can be used to modify the behavior of the network. Our main results provide controllable bounds on the level of synchrony of the network. The problem ofselecting the feedback parameters to achieve the desired bounds is also addressed and the approach is applied to a number of neuronal network models. The application is motivated by the feedback control of pathological synchronization of neuron firing in the brain, often responsible for neurological diseases such as Parkinsons
Strategic Management of Flammable Boreal Forest Landscapes that are Subject to Large Scale Windstorm Damage
Keywords: Blowdown
Compounded disturbance
Natural disturbance
Operations research
Strategic planning
Wildfire

A linear programming model was developed and used to evaluate how best to manage blowdown disturbances when carrying out strategic forest management planning in the boreal forest region of Ontario. Blowdown occurs when strong winds disturb large areas of standing timber, often more than several 100 hectares in size. My model accounts for wildfire and natural blowdown burning processes that should be considered when deciding if, when and where to initiate harvesting, salvage logging or prescription burning operations in order to maximize the economic value of the forest. Sound blowdown management calls for a mix of salvage logging, prescription burning and leaving some blowdown areas alone. My results suggest that some large blowdown disturbances should be set aside and neither salvage harvested nor prescription burned. Current policy may be inadequate at preparing forest managers for multiple large, infrequent and uncertain disturbance events as contingency may need to be increased at least two-fold.
Lanthanum-mediated Aminoacylation on Dinucleotides
Keywords: Aminoacylation
dinucleotide
Lanthanum
tRNA

Developing methods that can insert unnatural amino acids at specific locations within proteins is a topic of considerable recent interest. In vitro pathways using chemically aminoacylated tRNA have previously been developed. However, the multi-step protection and deprotection pose limits on this method. Biochemical methods have also been developed using orthogonal tRNA/aminoacyl-tRNA synthetase pairs. However, the variety of available unnatural amino acids is limited by the high specificity of aminoacyl tRNA synthetases. To overcome these problems, an improved chemical lanthanum-mediated aminoacylation method has been developed. Previous studies have shown the success of aminoacylating nucleosides/nucleotides with both protected and native amino acids. In this study, the reaction was studied with dinucleotides using N-t-Boc-protected aminoacyl ethyl phosphates. Successful aminoacylation on dinucleotides was observed. Optimal pH and buffer compositions were determined for this reaction. These results are expected to provide information in developing a lanthanum-mediated catalytic chemical method to unnatural aminoacylated tRNA in general.
Clinical and Biological Studies of the Alternative Lengthening of Telomeres in Paediatric Brain Tumours
Keywords: Alternative Lengthening of Telomeres
ATRX
C-circles
Paediatric Brain Tumours
Survival
TP53

Certain cancers maintain telomeres using the alternative lengthening of telomeres (ALT), which is associated with mutations to specific genes in several cancers. ALT has not been characterized in paediatric brain tumours (PBTs).We hypothesized that ALT is present in PBTs, is associated with mutations to ALT-associated genes, and impacts survival.517 PBTs and 163 control tumours were screened for ALT using the c-circle assay.ALT was found in high grade PBTs of mesenchymal/neuroepithelial tissue origin characterized by a high incidence of mutant TP53. ALT was associated with TP53 (p = 7.32x10-8) and ATRX (p = 5.23x10-4) mutations. ALT abrogated poor survival in TP53 mutant paediatric malignant gliomas (p = 0.03). Association with improved survival approached significance in TP53 mutant choroid plexus carcinoma (p = 0.07).ALT is found in PBTs harboring somatic TP53 mutations, and impacts survival. Stratification using ALT is important for the management of these cancers in children.
Landscape Influences on Hydrological Transit Times in Precambrian Shield Catchments
Keywords: catchment modelling
hydrology
isotope tracers
mean transit time
water management
watersheds

The estimation of mean transit times (MTTs) is regarded as a powerful descriptor of catchment systems since it provides broad information about hydrological mixing and storage processes in a single encompassing measurement. In this study, convolution lumped modeling was incorporated into the R programming language. Approximately 3.5 years of precipitation and streamflow water isotope signatures were used to estimate transit times across six Precambrian Shield catchments in the Muskoka-Haliburton region of south-central Ontario. The main objective of this study was to explore the main physical controls governing catchment-scale transit times by investigating relationships with light detection and ranging (LiDAR)-based landscape metrics. The MTTs were best correlated to topographic metrics such as flow path gradient and the ratio of flow path length to gradient (i.e. L/G index). These findings support the notion that within shallow-soil catchments in the Precambrian Shield region, it is topography, especially gradient-driven metrics, which is most meaningful in dictating catchment-scale water storage and movement.
A High-throughput Screen for Novel Genes Involved in Maintaining Genome Stability and the DNA Damage Response Pathway in Saccharomyces cerevisiae
Keywords: Cancer
DNA damage
Genome Instability
Ribonucleotide reductase

Oncogenesis is frequently accompanied by rampant genome instability, which fuels genetic heterogeneity and resistance to targeted cancer therapy. I have developed an approach that allows precise, quantitative measurement of genome instability in a high-throughput format in Saccharomyces cerevisiae. My approach takes advantage of the strongly DNA damage-inducible gene RNR3, in conjunction with the Reporter Synthetic Genetic Array methodology, to infer mutants exhibiting genome instability by assaying for increased Rnr3 abundance. We screen for genome instability across ~4200 non-essential mutant yeast alleles in untreated conditions and in the presence of the DNA damaging agent MMS. Our results provide broad insights into the cellular processes and pathways required for genome maintenance. Preliminary follow-up work suggests that several genes have bona fide roles in the maintenance of genome stability. In addition, I conducted both screens in their entirety on two, highly orthogonal fluorescence imaging platforms and compared their reproducibility and sensitivity.
Using Tendon Vibration between Trials to Alter Proprioceptive Sensitivity and its Influence on Upper-limb Control during Voluntary Reaching
Keywords: multisensory integration
online control
proprioception
tendon vibration

The current study investigated the effects of a novel tendon vibration method on upper-limb position sense and upper-limb rapid movement control. The relative contributions of proprioception and vision during action were assessed. Vibration of elbow extension muscles was applied between trials to avoid reflexive activations that typically occur with vibration during movement. In the position-sense task, participants were asked to move the non-vibrated arm to match the position of the vibrated arm. In the action task, participants were asked to perform a discrete reaching movement. Vibration was found to decrease position sense precision and yielded increased trajectory variability towards the end of the movement. Notably, the influence of vibration on trajectory variability was also observed for reaches made in the presence of vision. Tendon vibration presented between trials likely perturbs proprioceptive feedback during trials. Also, it is concluded that proprioceptive information contributes significantly to the control of visually guided movements.
Development of a General Dynamic Multimedia Indoor Model for SVOCs: Applications to PBDEs
Keywords: Fugacity model
Indoor environment
Multimedia model
Polybrominated diphenyl ethers
Polyurethane foam
Unsteady-state model

An unsteady-state, fugacity-based, indoor chemical fate model was developed to explore kinetic resistance of multilayer of polyurethane foam (PUF) commonly found in upholstered furniture. The Dynamic Layered PUF Simplified Multimedia Indoor Model (DLP-sMIM) was based on the Multimedia Indoor Model created by Zhang et al. (Zhang, Diamond et al. 2009). DLP-sMIM was applied to real and hypothetical scenarios indoor environments consisting of air, carpet, PUF furniture and the surface film on walls. The model showed good agreement with reported concentrations from a study of indoor polybrominated diphenyl ethers (PBDE) air concentrations over nine months. The PUF compartment was predicted to experience long PBDE residence time. It is suggested that steady-state models and using the well-mixed assumption for a single PUF compartment causes an orders-of-magnitude overestimation of the mass of chemicals in PUF. Rather, two vertical layers of PUF need to be considered in a time-dependent model of indoor chemical fate.
Robust Control of Active Ankle Torque during Quiet Stance: a Servomechanism Problem
Keywords: Quiet Stance
Robust Control
Servomechanism

Treatment and restoration of motor abilities to individuals with spinal cord injury (SCI) is possible with neuro-rehabilitative systems for unsupported upright stance, also known as quiet stance. The aim of this research project is to develop a controller that will regulate active ankle torque during electrical stimulation for quiet stance. This study uses a novel technique of applying an optimal robust servomechanism controller to bring the human's centre of mass (COM) to a specified reference position independent of external disturbances. The robust controller obtained was able to track quiet stance within 1 second, and highly attenuate both constant and Gaussian noise disturbances intensity. The robust controller presented can be considered as a step forward in neuro-rehabilitative systems for quiet stance, as previous controllers have not considered dealing with the servomechanism control problem in the regulation of ankle torque.
Mothers' Explicit and Implicit Moral Identity, Parenting and Adolescent Moral Development
Keywords: Moral Development
Moral Identity
Moral Values
Parenting
Socialization

Grusec and Goodnow (1994) proposed a framework wherein children's internalization of values depends upon the accurate perception and acceptance of parents' values. The present research attempted to demonstrate the utility of the proposed framework. Using a longitudinal approach with measures taken at two time points, reasoning, directiveness and ignoring misbehaviour were examined as potential moderators of the relation between maternal moral identity, explicit and implicit, and adolescents' internalization of moral values. Two measures of adolescent internalization were used: mother-adolescent value congruency and adolescent relative autonomy. The results indicated that higher levels of reasoning moderated the relation between maternal implicit moral identity and adolescent moral values, lower levels of directiveness moderated the relation between maternal explicit moral identity and adolescent moral values, and lower levels of ignoring misbehaviour moderated the relation between maternal explicit moral identity and adolescent relative autonomy. The theoretical and practical implications are discussed.
Preparation of Polypropylene Foams with Micro/Nanocellular Morphology using a Sorbitol-based Nucleating Agent
Keywords: Bead foaming
Extrusion fomaing
Microcellular
Nanocellular
Polypropylene foam
Sorbitol

The effect of a sorbitol-based nucleating agent on expanded polypropylene (EPP) bead foaming and extrusion foaming was investigated. The main purpose of this study was to study and develop a fundamental processing baseline for the production of nanocellular foams.During the EPP bead foaming experiments using different concentrations of a sorbitol-based nucleating agent, NX8000, foams having a sub-micron sized cells (
Cyclosporin A Promotes Neural Precursor Cell Survival to Enhance Neurogenesis in the Hippocampus
Keywords: cyclosporin A
hippocampus
neural stem cells
neurogenesis

Neural precursor cells (NPCs) in the adult mammalian brain show potential in applications of regenerative repair in the CNS. Recent work has shown that Cyclosporin A (CsA), a commonly used immunosuppressive drug, expands the size of the NPC pool in the lateral ventricle subependyma by promoting cell survival, with no concomitant effect on proliferation kinetics. We asked if CsA had similar effects on neural precursors in the neurogenic dentate gyrus within the hippocampus. In vitro, we found that CsA increases the size of the NPC pool. Our in vivo studies reveal an increase in proliferating immature neurons in mice subcutaneously infused with CsA for seven days. A time course study reveals that CsA promotes the survival of newly born NPCs, which can then go on to form new neurons in the DG. Together these findings support the hypothesis that CsA administration promotes neurogenesis and may have implications for tissue repair following injury.
Value Impacts of Energy Efficiency Retrofits on Commercial Office Buildings in Toronto, Canada
Keywords: Buildings
Commercial
Energy
Retrofit
Sustainability
Value

The intent of this thesis is to strengthen the business case for sustainable building in Canada by studying the relationship between building energy efficiency and value. This is accomplished through detailed examination of four Toronto commercial office building retrofit case studies with quantitative pre- and post-retrofit energy and financial data. The income capitalization approach to building appraisal is adopted as a model for linking sustainability to value through net operating income. The results suggest that retrofitting buildings can decrease operating costs, increase occupancy rates, and increase effective rent (rental revenue), thereby increasing net operating income. These benefits are not necessarily achieved in every retrofit; however where these benefits do occur, they have positive effects on value.
Diffusion of Methodological Innovation in Pharmacoepidemiology: Self-controlled Study Designs
Keywords: innovation
pharmacoepidemiology
research methods
self-controlled

Self-controlled designs are methodological innovations that complement traditional observational studies and are useful to control for time-invariant confounders. The use and diffusion of self-controlled case-control and cohort designs in pharmacoepidemiology was examined over time, and described using Rogers' Diffusion of Innovations Theory and co-authorship network analysis (visualized in a supplementary graphics interchange format (GIF) image). Studies experienced a lag in diffusion, followed by a rapid uptake in use since 2000. Overall, the co-authorship network was comprised of 176 papers, 763 authors and 46 components; 31 components contained one paper (61% self-controlled case-control). The largest component of the network was interconnected and was comprised of 69% self-controlled cohort studies. Future work to develop and disseminate standardized language could target seminal authors and key opinion leaders identified in the network. Formal reporting guidelines are also encouraged, as the majority of applications did not follow recommendations on reporting, such as raw data display.
The Role of DNA Damage Sensing Genes in Genetic Instability and Radioresponse in Prostate Cancer
Keywords: Copy-number alterations
DNA Damage Response
DNA Repair
Genomics
Prostate Cancer
Radiation Therapy

Prostate cancer (PCa) is the second cancer-related mortality cause in North American men. Despite the use of clinical prognostic factors, 20-60% of localized PCa fail primary local treatment. There is need for biomarkers that can guide primary treatment decisions or identify patients that need treatment intensifications. I have hypothesized that localized PCa is associated with an altered DNA damage response (DDR), which in turn can lead to genomic instability and affect the response to radiotherapy. Using array comparative genomic hybridization I have determined the frequency and prognostic importance of copy-number alterations (CNAs) in the main sensors of the DDR. I have shown that CNAs in these loci correlate with tumour genomic instability. The main finding is that Nibrin gains are a significant predictor of outcome following treatment with radiotherapy, but not surgery. NBN gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches.
Social Participation, Self-Perception, and Social Support in Boys Living with Hemophilia
Keywords: Health-related Quality of Life
Hemophilia
ICF
Self-Perception
Social Participation
Social Support

Social integration is a critical component of quality of life and understanding how persons with hemophilia interact socially with their peers may inform healthcare providers.A random sample of 50 boys with hemophilia from The Hospital of Sick Children completed measures of social participation, self-perception, and social support. Participants' parents completed a measure assessing the impact of chronic illness on the family.The majority of boys reported no significant participation restrictions. Social participation was strongly correlated with self-perception subscales Social Acceptance and Global Self-Worth. The Athletic Competence subscale was strongly correlated for adolescents only. There were strong correlations between social participation and social support from parents, teachers, and classmates and moderate correlations for support from close friends. There was minimal impact on the family and weak correlations between social participation and impact on the family.Boys with hemophilia have minimal social participation restrictions and are on par with their peers.