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    123129 research outputs found

    Exploration of pathogen-inactivation conditions in container-based composting of dry toilet feedstocks for decentralized sanitation

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    Decentralized technologies can help alleviate sanitation needs in resource-constrained environments lacking basic services. Peri-urban areas can be an example due to their inherent dynamic characteristics that can exceed governments’ capacity to respond with the required infrastructure such as piped water and sewerage. The initial stage of this project involved understanding the sanitation needs in a Mexican peri-urban community by using toilet sensors developed for that purpose, and the insights pointed to the possibility of dry sanitation alternatives that could be implemented at a household scale. One such technology is the urine-diverting dry toilet with feedstock composting as a means of waste management. When centralized composting services are unavailable, household-scale composting can be a suitable alternative, however, poorly managed compost piles can present a pathogen exposure risk for both users and workers. Thus, a better understanding of the composting process can help improve the barriers against pathogen exposure and reduce the associated risks. The core objective of this project is to explore the conditions required to achieve pathogen-inactivation temperatures of dry toilet feedstocks in small volumes through container based designs. A simplified analytical model that describes the composting process was developed and used as a simulation tool to define the operational space for the container-based systems. The model is based on biodegradation kinetics and heat losses. By focusing on the compost temperature as the main output parameter instead of oxygen demand, the experiments used for calibration could be designed for ease of construction and replication. The experiments also helped define the required feedstock handling protocols, suitable organic materials and the main parameters balance. The results showed that pathogen-inactivation temperatures can be achieved for a self-heating, small-volume, container-based composting system at a household scale, using off-the-shelf, readily available components, thus making the proposed design accessible for researchers and practitioners in resource-constrained environments. The results presented in this project can help advance the development of waterless sanitation systems, leveraging the use of decentralized, household-scale, feedstock management.Ph.D

    A Novel Approach to Discover Cryptic Drug-Binding Pockets In Silico

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    Cryptic pockets are ligandable pockets that are not apparent in ligand-unbound protein structures and are only seen upon ligand binding. They provide compelling opportunities for drug discovery, such as providing a means to target proteins otherwise thought to be undruggable or developing compounds with greater selectivity. Current computational methods for cryptic pocket discovery typically rely on slow molecular dynamics (MD) simulations. Although there has been attempts to accelerate cryptic pocket discovery using advanced MD methods, there has been mixed reports of success and recurrent challenges. Here, a new strategy is introduced to accelerate the process by rapidly guiding MD simulations towards the open state of cryptic pockets. The method was implemented on the unbound structures of five proteins with known cryptic pockets, and its ability to produce open and druggable conformations of the cryptic pocket more efficiently than conventional unbiased MD simulations was assessed. Success was observed in four cases, and clear determinants of success and paths for improvement have been established.M.Sc

    MRI Monitoring Strategies for Cardiac Repair Therapies in Myocardial Infarction

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    Myocardial infarction (MI) is the most common cause of heart failure (HF). Cardiac regenerative therapies, including injection of pluripotent stem cell-derived cardiomyocytes (PSC-CM), offer a promising alternative to restore heart function. Imaging biomarkers that can resolve graft local structure and function of the heart may be useful in guiding and evaluating such therapies. However, their translation to clinical practice requires rigorous evaluation of graft-host integration, therapeutic efficacy, and impact on myocardial structure and function. This dissertation develops and employs magnetic resonance imaging (MRI) to comprehensively assess the structural and functional outcomes of PSC-CM therapy in a guinea pig model of MI.The first aim of this work was to characterize the microstructural properties of immature and mature PSC-CM grafts using diffusion tensor imaging (DTI). Mature PSC-CMs exhibited a similar fractional anisotropy and mean diffusivity to that of healthy tissue. These findings showcase the utility of DTI to characterize exogenous PSC-CMs in an ex vivo guinea pig model of MI. The second aim focused on evaluating the longitudinal functional effects of PSC-CM therapy using cine MRI and late gadolinium enhancement (LGE). PSC-CM-treated guinea pig hearts demonstrated attenuated LV remodeling, preserved end-systolic and end-diastolic volumes, and significantly improved regional wall thickening in scar+graft regions compared to vehicle-treated controls. While ejection fraction trends were positive, structural and functional stabilization highlighted the therapeutic potential of PSC-CMs in mitigating post-MI remodeling. The third aim integrated DTI and cine MRI to establish structure-function correlations between PSC-CM graft characteristics and cardiac recovery. Lower mean diffusivity in graft regions correlated with enhanced wall thickening, while greater helix angle transmurality in remote myocardium was associated with reduced LV dilation. These results reveal the mechanistic role of PSC-CM structural integration in improving cardiac function and demonstrate the utility of imaging biomarkers for monitoring regenerative therapies. This work establishes MRI as a platform for evaluating the efficacy of regenerative therapies, providing insights into the structural and functional mechanisms underlying PSC-CM therapy. This dissertation paves the way for future studies using MRI for preclinical applications of cardiac regeneration.Ph.D

    Compton Scattering Calibration For Cryogenic Silicon Calorimeters

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    The nature of dark matter remains unknown, with no experimental confirmation of existing theories. The upcoming SuperCDMS SNOLAB experiment seeks to probe dark matter particle models with masses below 10~GeV/c^2. To achieve this, the SuperCDMS collaboration has developed cryogenic sampling calorimeters with energy thresholds down to the sub-eV energy range. The response of the SuperCDMS detectors is not fully characterized theoretically, requiring empirical calibration techniques down to their energy thresholds. A key challenge for an empirical calibration technique is to achieve a uniform distribution of energy depositions throughout the detector target, as expected from dark matter particles. This thesis presents the development of a novel calibration technique for SuperCDMS silicon detectors utilizing energy signatures from the Compton scattering energy depositions. The simulations supporting this calibration method are discussed. Additionally, the inference model to identify the calibration signatures in the data, and the procedure to construct the calibration function is described. This thesis further demonstrates a successful calibration of experimental data from four SuperCDMS R&D detectors using this approach. Finally, a comparison is made between the new method and an alternative calibration technique using optical photons (2 eV).Ph.D

    Points-Based Valuation for Property Taxation: Improving Equity and Revenue Performance in Local Property Tax Systems

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    Many property tax systems in lower-income countries are severely underperforming, in significant part due to ineffective valuation methods. This brief outlines a points-based approach to valuation, which offers a cost-effective, administratively feasible, and transparent approach to valuation in lower-income countries

    Using history matching to speed up Management Strategy Evaluation grid searches

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    Management Strategy Evaluations (MSEs) are a valuable tool for assessing the performance of different management strategies under varying ecological and economic conditions. They can be used to optimise the management procedure. However, MSEs are computationally demanding, especially as the complexity of operating models increases. I propose a scheme based on history matching to speed up grid searches when looking to optimise control parameters in harvest control rules. The approach uses an emulator, a fast statistical model that mimics the MSE, to exclude points that have a high probability of not being the optimal. The emulator is updated until only one point remains. The methods are introduced and demonstrated using an MSE on North Sea cod. Typically, the method found the optimal solution with only 9\% of the grid evaluated in 12\% of the clock time. I compared history matching with alternative optimisation algorithms, including hill climbing, simulated annealing and the genetic algorithm, and found that history matching consistently outperformed the alternatives.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author

    Changes of soil test phosphorus and phosphorus fractions with single and blended soil chemical amendments

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    Supplementing phosphorus (P) is essential for crop production, but excessive P becomes a pollutant through soil-to-waterway losses. Soil amendments can stabilize P and reduce dissolved P losses in runoff. While single-amendment applications have been extensively studied, the effectiveness of blended amendments in decreasing soil P loss remains largely unexplored. This study evaluated the effects of single and blended applications of alum [KAl(SO4)2·12H2O], ferric chloride (FeCl3), gypsum [CaSO4·2H2O], and magnesium sulphate (MgSO4) on soil P status and transformations in six agricultural soils from southern Manitoba. Fresh soils treated with fifteen amendment treatments, including an unamended control, were incubated at 22 ±1The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author

    Performance of ChatGPT-4o in Determining Radiology–Pathology Concordance and Management Recommendations Following Image-Guided Breast Biopsies

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    Background: Determining radiology–pathology concordance after breast biopsies is critical to ensuring appropriate patient management. However, expertise and multidisciplinary input are not universally accessible. Purpose: To evaluate the performance of a large language model, ChatGPT-4o, in determining the radiology–pathology concordance of breast biopsies and suggesting subsequent management steps. Methods: A retrospective single-center study analyzed 244 cases of image-guided breast biopsies of women. ChatGPT-4o assessed de-identified radiology and pathology reports for concordance and recommended management. Radiologist assessments served as the reference standard with final surgical pathology and 2-year imaging follow-up serving as gold standards when applicable. Concordance rates, management recommendations, and diagnostic agreement with the gold standard were compared using statistical tests, including McNemar’s, chi-square, Fisher–Freeman–Halton, and Cohen’s kappa. Results: ChatGPT-4o achieved a concordance rate of 98.8% vs. 98.0% for radiologists (p = 0.625) and demonstrated high diagnostic agreement with the gold standard (kappa = 0.947, p < 0.001). ChatGPT-4o favored imaging follow-up more than radiologists (49.2% vs. 41.8%, p < 0.001) and surgical management less frequently (41.8% vs. 46.7%). Conclusions: ChatGPT-4o demonstrated diagnostic performance comparable to radiologists with breast imaging subspecialities in evaluating breast biopsy concordance. Its slightly more conservative management approach may enhance shared decision-making in resource-limited settings

    Guide de préparation à la migration vers Scholaris: Préparer votre institution au passage à Scholaris

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    Cette ressource fournit des considérations et des étapes suggérées pour les institutions universitaires intéressés ou envisageant de rejoindre Scholaris, un service partagé national de dépôt institutionnel facultatif basé sur la plateforme DSpace et hébergé et géré de manière centralisée par Scholars Portal. Ce guide a été élaboré à partir des commentaires partagés par les institutions participants au programme d'adoption précoce de Scholaris lors d'entretiens individuels préalables à la mise en œuvre, entre juin et octobre 2024

    Exploring the Cytokinin Profile of Doliocarpus dentatus (Aubl.) Standl. From Guyana and Its Relationship with Secondary Metabolites: Insights into Potential Therapeutic Benefits

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    Background/Objectives: Possessing red and white ecotypes, and utilized in traditional Guyanese medicine, Doliocarpus dentatus’ red ecotype is preferred locally for its purported superior therapeutic efficacy. Although therapeutic metabolites were detected in D. dentatus previously, phytohormones remain largely unexplored, until now. Cytokinins, phytohormones responsible for plant cell division, growth and differentiation, are gaining traction for their therapeutic potential in human health. This study screened and quantified endogenous cytokinins and correlated detected cytokinins with selected secondary metabolites. Methods: Liquid chromatography–mass spectrometry was used to acquire phytohormone and metabolite data. Bioinformatics tools were used to assess untargeted metabolomics datasets via statistical and pathway analyses, and chemical groupings of putative metabolites. Results: In total, 20 of the 35 phytohormones were detected and quantified in both ecotypes, with the red ecotype displaying higher free base and glucoside cytokinin concentrations and exhibited 6.2 times the total CK content when compared to the white ecotype. Pathway analysis revealed flavonoid and monoterpenoid biosynthesis in red and white ecotypes, respectively. Positive correlations between specific cytokinins and alkaloids, and between trans-Zeatin and isopentenyladenosine riboside with phenolic compounds were observed. Conclusions: These results suggest that the red ecotype’s elevated cytokinin levels coupled with flavonoid biosynthesis enrichment support its preference in Guyanese traditional medicine

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