30921 research outputs found
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Translational investigation of novel antimicrobial agents against bacterial infection
No full textAntimicrobial resistance (AMR) among bacterial pathogens has become a daunting threat to human health. Developing new and effective drugs or strategies to counteract antibiotic resistance is urgently needed. This research aimed to identify active compounds derived from natural sources. Previous research demonstrated that Paenibacillus polymyxa J, a plant symbiotic bacterium, produces an unidentified compound that exhibits potent bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to extract, purify, and identify the antimicrobial compounds produced by P. polymyxa J.
The bacterial cells were cultivated on a large scale using a bioreactor, and the compounds produced by the bacteria were extracted using an organic solvent. High-performance liquid chromatography (HPLC), equipped with two different detectors, the diode array detector and the evaporative light scattering detector (ELSD), was used to detect, separate, and isolate 4 interesting antimicrobial bioactive peaks. Further characterization assays, such as nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), liquid chromatography with tandem mass spectrometry (LC-MS-MS) and gas chromatography/mass spectrometry (GC/MS) were performed on these fractions to determine the structure of compounds. The tentative molecular structures were obtained from the data and used to compare with databases to dereplicate and confirm the presence of any novel compounds. Consequently, at least one novel bioactive compound was identified.
In addition, proteomics analysis was done on 3 phases of Paenibacillus polymyxa J’s growth, including the 1) log and 2) stationary phases from broth culture and 3) solid medium. Potential gene clusters at specific regions in the genome that could potentially be responsible for producing antimicrobial compounds of interest were identified using antismash. Using the antismash and omics data, the protein changes during the different growth phases were obtained. As a result, potential gene clusters responsible for the 4 mentioned compounds of interest were determined. The findings of this research can serve as a foundation for further investigation.October 202
Reinforcement learning approach for optimizing load shedding and controller parameter tuning in active islanded power systems
No full textThe rising frequency of extreme weather events associated with climate change has made the resilient design an important feature for power systems. Incorporating the capability of parts of the power system to operate as active decentralized systems is one way of increasing the resiliency and enhancing the system reliability. This thesis addresses two significant issues related to decentralized active networks.
The first issue concerns the challenge of maintaining the balance between generation and load within an islanded system through under-frequency load shedding (UFLS) during islanding events. The optimal design of UFLS schemes in active networks presents a complex problem, especially with the high penetration of inverter-based resources (IBR) that exhibit complex dynamics and low inertia. It is also important to ensure that the system operates effectively at any given operating point, necessitating the consideration of multiple operating points in the design process. Conventional schemes and control methods may not be sufficient and identifying a suitable scheme can be both time-consuming and labor-intensive, often requires conducting many simulations at various operating points. This thesis presents an optimal load shedding method in active decentralized power systems using reinforcement learning. The effectiveness of these proposed methodologies is demonstrated through the implementation of a UFLS system on a segment of the Manitoba Hydro power network.
The second significant issue addressed in this context is the tuning of controllers for active, decentralized systems. These controllers need to be adjusted to function optimally across a wide range of operating conditions, both in grid-connected and islanded modes. This poses numerous challenges due to the systems' complexity and dynamic nature and traditional heuristic controller tuning methods often prove inadequate in managing such complexities. In response, this thesis proposes a novel approach that extends the ideas of deep reinforcement learning to tune controllers across multiple operating scenarios. The validity of the proposed method is illustrated through tuning of Proportional-Integral (PI) controllers for battery energy storage systems within the modeled systems. While these developed methods are showcased on a section of the network, it can be expanded to larger power networks, providing scalability to the operation of power systems.October 202
Correction: Areas of consensus on unwarranted and warranted transfers between nursing homes and emergency care facilities in Norway: a Delphi study
No full textUnderstanding how triple-negative breast cancer cells respond to chemotherapy
No full textEvery year over 5,000 Canadians are diagnosed with Triple-Negative Breast Cancer (TNBC), an aggressive subtype of breast cancer with limited treatment options and a poor patient prognosis. The main treatment for TNBC is neoadjuvant chemotherapy followed by tumour resection, and while this can be effective for many patients, there remains a significant number of individuals that experience tumour relapse within 3-5 years post-treatment. Understanding the reason behind frequent relapse is vital in designing novel and effective therapeutic strategies. To this end, we must first elucidate how TNBC cells are responding to standard-of-care chemotherapeutic treatment to better understand the changes that lead to tumour relapse. The objective of my study is to analyze how TNBC cells respond to a clinically-relevant dosage of the commonly used chemotherapeutic, paclitaxel. To achieve this, we used the TNBC cell line, MDA-MB-231, to assess transcriptomic, proteomic, secretomic, and functional changes in response to a clinically-relevant low dosage of the chemotherapeutic paclitaxel. We discovered several gene expression changes in paclitaxel-treated cells that are seen in pro-tumourigenic processes including cancer stem cell expansion, epithelial-mesenchymal transition (EMT), metastasis, and inflammatory signaling. Functional assays of paclitaxel-treated MDA-MB-231 cells confirmed alterations to functional characteristics consistent with the upregulation of genes involved in stemness and inflammatory signaling. However, despite pro-EMT gene expression changes, paclitaxel-treated cells displayed a reduction in migration. These findings propose that MDA-MB-231 cells treated with low-dose paclitaxel undergo alterations in gene expression linked to processes that may support tumour relapse.May 202
Responding to survivors: confronting epistemicide within genocide education in Canadian post-secondary institutions
Get PDFThis thesis promotes Indigenous-led education to address genocides by Canada against Indigenous Peoples of Turtle Island and aims to advance supportive, equitable, and liberatory community relationships. My focus is on how genocide educators, the Canadian post-secondary institutions they work in, and the wider community connected to them are practicing relationality and might build on the practices examined.
This desire to learn comes out of the knowledge that better responses to Survivor redress are needed. Genocide education in Canadian post-secondary institutions has a colonial problem that needs further unsettlement. This colonial problem includes an attempt to violently erase Indigenous Peoples both inside and outside of the academy in both material and symbolic ways. A significant part of this colonial problem in the educational context is epistemicide which involves the destruction of Indigenous knowledges and existence, which are inextricably intertwined. The Truth and Reconciliation Commission (TRC) and the National Inquiry into Missing and Murdered Indigenous Women, Girls, and 2SLGBTQQIA+ people (NIMMIWG2S +) have helped bring the discussion of settler colonial genocide in Canada to the forefront. These bodies have called for improved education that centres Survivors on the violence of Canadian settler colonialism, giving impetus to the need for assessment of the progress to date in genocide education in Canadian post-secondary institutions. This thesis explores the question: How are Canadian settler colonial genocides included in or excluded from post-secondary genocide education? It does so with the intent to inform future educational practice. Through my assessment of genocide program and course curricula related to genocides as used in Canadian higher education, I look for patterns and meaningful practices that form relationships with the territories in which it is being taught, as well as the Indigenous Peoples who have lived there since time immemorial. I then draw on theories of settler colonialism and Indigenous methodologies to better understand how these observations might connect to relational accountability. My results show that some practices are connected to ethical relationality, yet overall, much change is needed to confront epistemicide and centre Survivors.October 202
Review of clinical trials and guidelines for children and youth with mucopolysaccharidosis: outcome selection and measurement
Get PDFAbstract Background To inform the development of a core outcome set (COS) for children and youth with mucopolysaccharidoses (MPS), we aimed to identify all outcomes and associated outcome measurement instruments that are reported in recent clinical trials and recommended as measurements in clinical management guidelines. Methods To identify English-language clinical trials and guidelines pertaining to MPS published between 2011 and mid-2021, we applied a comprehensive peer-reviewed search strategy to relevant databases and registers on May 16, 2021. Two reviewers independently screened retrieved citations and then full-text articles to determine eligibility for inclusion. From articles meeting inclusion criteria, we extracted details of the study design, population, intervention, and comparator, along with verbatim outcomes and associated outcome measurement instruments. Outcomes were organized into domains within five a priori core areas: life impact, pathophysiological manifestations, growth and development, resource use, and death. We conducted descriptive analyses at the study level, grouping articles arising from the same study. Results From 2593 unique citations, 73 articles from 61 unique studies were included in the review, pertaining to all MPS subtypes except for exceptionally rare subtypes. Eighty-four unique outcomes were reported across the studies, 33 (39%) of which were reported by three or fewer studies. Most outcomes (55; 65%) were in the pathophysiological manifestations core area, followed by life impact (17; 20%) and growth and development (10; 12%); one outcome each pertained to resource use and death. The most frequently reported outcomes were general adverse events (45; 74%), immune-related adverse events (39; 64%), and urinary glycosaminoglycans (38; 62%). Substantial variability existed in the reporting of outcome measurement instruments. Some differences in outcome reporting were observed by MPS subtype and publication year. Discussion Outcomes reported in clinical trials and guidelines for MPS in children and youth vary considerably and largely focus on pathophysiological manifestations. A COS is needed to standardize the selection and measurement of meaningful outcomes across future studies. We will present the outcomes identified in this review to knowledge users as part of a consensus process to select the most critical outcomes for inclusion in the COS. Trial Registration The protocol for this study was registered in PROSPERO (CRD42021267531) and in the COMET Database
Stochastic optimization of a closed-loop fashion supply chain.
Get PDFThe fashion industry, characterized by rapid changes in consumer preferences, high demand volatility, and intense global competition, faces challenges in maintaining profitability while addressing sustainability concerns. The fast-changing nature of fashion trends leads to a high turnover of products, contributing to waste and environmental degradation. These issues underscore the need for fashion companies to adopt sustainable practices and enhance their supply chain management to remain competitive and ecologically responsible. This research proposes a novel mathematical modeling approach aimed at minimizing the cost of fashion companies within a closed-loop supply chain framework, incorporating sustainability considerations, and addressing uncertainties through stochastic optimization.
In the fast fashion industry, companies grapple with fluctuating consumer demands and the imperative for environmental stewardship. The perishability of fast fashion exacerbates waste, as products quickly fall out of favor, leading to environmental impacts. This thesis emphasizes the necessity of transitioning towards sustainable practices within the fashion industry, advocating for implementing closed-loop supply chains to mitigate environmental degradation while optimizing efficiency and profitability.
We introduce deterministic and stochastic models tailored for the fashion industry. Our approach uses two-stage stochastic optimization to manage uncertainties in demand within the closed-loop supply chain. This model incorporates sustainability into supply chain practices, reducing environmental harm and enhancing resilience and adaptability in the face of market volatility. Furthermore, a comparative analysis of the deterministic and stochastic model results underscores the importance of accounting for demand uncertainty in optimizing fashion supply chain operations.
Central to our methodology is the Sample Average Approximation (SAA) method, employed to solve the two-stage stochastic problem presented by the supply chain's dynamics. The SAA method is chosen for its robustness in handling uncertainty and its capacity to provide actionable insights based on empirical data. By applying this method, I demonstrate the feasibility of our model in real-world scenarios, guiding fashion companies toward sustainable practices without compromising profitability. This study adds to the knowledge of sustainable fashion by providing a practical solution to sector problems. Integrating sustainability and mathematical modeling opens the door to a more successful fashion business where economic goals and environmental concerns are both addressed.October 202
Characterization of manure management, nutrient composition, and greenhouse gas emissions from cow-calf operations in Manitoba
No full textThis research was conducted to characterize management practices on Manitoba cow-calf operations, as well as nutrient composition and greenhouse gas emissions from solid beef cow manure during summer storage. A survey of management practices, including animal and manure management, was conducted on 10 cow-calf operations across Manitoba, which were known to generate stored solid manure from beef cows. Physical characteristics and nutrient composition of manure were measured on 2-3 dates, and manure greenhouse gas emissions (CO2, CH4, N2O, NO2, and NH3) were measured approximately biweekly over four months using a steady-state, flow-through hood with an in-line FTIR multi-gas analyzer. Farm calving season and manure disturbance (piling and/or mixing) were management practices which influenced the quantity and timing of GHG emissions, in that manure stored in piles had higher CH4, N2O, and reactive N gas, NO2 emissions, than manure in bedding packs, on a per area of manure basis (CO2-e m-2 ). Average cumulative CO2 flux for manure stored in piles ranged from 4,319.0-25,276.1 g m-2 per month, as compared to 375.3-1,628.3 g m-2 for manure stored as a bedding pack. Across all farms, CH4 was responsible for the largest proportion of emissions, with a mean whole-period cumulative flux of 771.9 g m-2 or 19,298.0 g CO2-e m-2 across all farms. Understanding the influence of management practices on manure composition, degradation, and GHG emissions will help position the cow-calf sector towards sustainability through the development of GHG emission models, improved emissions estimates, and the development of best management practices for producers. Not all manure storage types were captured (e.g., true composting of manure) and therefore additional research in this area will allow for improved understanding of chemical processes/mechanisms responsible for observed GHG emissions.October 202
Two essays on the impact of automation on firms' operating performance and M&A decisions, and one essay on a comparative analysis in external financing between U.S. and Japan
No full textThis thesis includes three topics on corporate finance: (1) Automation Exposure and Operating Performance, (2) Corporate Cash Shortfalls and External Financing: US vs Japan, and (3) Automation Exposure and M&A.
The first essay, "Automation Exposure and Operating Performance," finds empirical evidence that firms with increased automation exposure experience deteriorating operating performance in subsequent years. Further analysis shows that financially unconstrained firms are better positioned to mitigate this negative impact on their operating performance compared to financially constrained firms. However, unconstrained firms are drawn into an automation arms race, escalating their investments in capital, tangible assets, and R&D. This race, while aimed at maintaining a competitive edge, paradoxically leads to a greater deterioration in their financial health compared to their financially constrained counterparts.
In the second essay, "Corporate Cash Shortfalls and External Financing: US vs Japan," I find supporting evidence for the funding-horizon theory on external financing in both the US and Japan. I also find that repurchase and subnormal cash holding are important motives for debt issuance, while debt reduction is an important motive for equity issuance. Japanese firms are much less likely to issue debt and equity compared to US firms. The results suggest that this difference is due to the lower leverage used by Japanese firms and the fact that Japanese firms tend to be mature with fewer cash needs for growth.
In the third essay, “Automation Exposure and M&A,” I find evidence that firms with high automation exposure are more likely to be involved in M&A transactions. High automation exposure firms with high R&D, profitability, cash holding, market value, and low leverage tend to be acquirers, while firms with the reverse characteristics tend to be targets. I further find that automation facilitates M&A transactions when product similarity is high. Consistent with the findings from my first essay on the automation arms race, acquisitions for automation purposes result in a "winner's curse," where the acquiring firms face greater financial constraints and lower operating profits in the following period.October 202
A First-Century Receipt from the Receivers of Public Clothing in Tebtunis (P.Tebt. UC 1607c)
No full textAn edition of a first-century Tebtunis papyrus containing a letter from the receivers of public clothing, with analyses of both this liturgical office as well as the practice of compulsory sale for the supply of military clothing