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LL-37 and citrullinated LL-37: differential modulation of the oxylipin - chemokine axis
No full textInflammation plays a crucial role in the host immune system, and it involves a complex network of cellular and molecular events. In the lungs, human bronchial epithelial cells release cytokines/chemokines, and other mediators such as bioactive lipids and cationic host defence peptides (CHDPs) to facilitate and regulate airway inflammation. Oxylipins are bioactive lipids that are key mediators in the process of inflammation. The human host defence peptide LL-37 enhances specific oxylipins such as prostaglandin E2 (PGE2) in fibroblasts and endothelial cells. LL-37 plays a pivotal role in inflammation by orchestrating both pro-and anti-inflammatory responses; LL-37 enhances pro-inflammatory chemokines, but also selectively suppresses inflammatory cytokines and help maintain immune homeostasis. However, the mechanisms that govern these opposing roles of LL-37 remain unclear. Under inflammatory conditions, LL-37 can get citrullinated, a post-translational modification that impairs its antimicrobial and antiviral functions. In this thesis, I investigate the interplay of LL-37 and oxylipins, and how that is altered by citrullination, in the context of airway inflammation. In this study, a lipidomics analysis was performed to profile oxylipins enhanced in the presence of LL-37 and citrullinated LL-37 (citLL-37) in in human bronchial epithelial cells (HBEC). Subsequently, these peptide-mediated chemokine productions were examined by ELISA, transcriptional analysis by qRT-PCR, and impact of peptide on neutrophil migration was examined in a transwell assay using neutrophils isolated from human blood. LL-37 significantly enhanced oxylipins such as PGE2, 11- and 15-HETE, 15-HETrE, and cytochrome P450-derived 9,10- and 12,13-EpOME. Whereas citLL-37 only enhanced 15-HETrE, 9,10 EpOME and 12,13-EpOME, oxylipins that negatively regulates inflammation. I showed that LL-37, but not citLL-37, enhances COX-2, a central upstream mediator of PGE2 in HBEC. Inhibition of COX-2 suppressed LL-37-induced neutrophil chemoattractants IL-8, MIP-3 and GRO, thus establishing the link between peptide mediated oxylipin and chemokine production. I functionally confirmed that inhibition of COX-2 impairs LL-37-mediated neutrophil migration. Overall, my findings suggest that citrullination of LL-37 mitigates the peptide’s ability to induce pro-inflammatory oxylipins and chemokines, thus this post-translational modification may be a molecular switch to control LL-37-mediated pro- and anti-inflammatory responses in the lungs.Canadian Institutes of Health Research (CIHR): Canada Graduate Scholarships- Master's (CGS M)October 202
Avian influenza virus circulation and immunity in a wild urban duck population prior to and during a highly pathogenic H5N1 outbreak
No full textAbstract Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses were first detected in St. John’s, Canada in late 2021. To investigate the patterns of avian influenza virus (AIV) infection and immune responses subsequent to the arrival of H5N1, we sampled the wild urban duck population in this area for a period of 16 months after the start of the outbreak and compared these findings to those from archived samples. Antibody seroprevalence was relatively stable before the outbreak (2011–2014) at 27.6% and 3.9% for anti-AIV (i.e., NP) and H5-specific antibodies, respectively. During the winter of 2022, AIV-NP and H5-specific antibody seroprevalence both reached 100%, signifying a population-wide infection event, which was observed again in late February 2023 following a second H5N1 incursion from Eurasia. As expected, population-level immunity waned over time, with ducks seropositive for anti-AIV-NP antibodies for approximately twice as long as for H5-specific antibodies, with the population seronegative to the latter after approximately six months. We observed a clear relationship of increasing antibody levels with decreasing viral RNA loads that allowed for interpretation of the course of infection and immune response in infected individuals and applied these findings to two cases of resampled ducks to infer infection history. Our study highlights the value of applying both AIV surveillance and seroprevalence monitoring to provide a better understanding of AIV dynamics in wild populations, which may be crucial following the global dissemination of clade 2.3.4.4b H5Nx subtypes to assess the threats they pose to both wild and domestic animals, and to humans
Parallelization of hybrid multi-objective evolutionary algorithm on multi-core architectures
No full textMany real world optimization problems involve multiple conflicting objectives, constraints and parameters. Multi-objective optimization (MOO) techniques are used to solve these problems. The goal of MOO is to find a set of optimal solutions, or the Pareto optimal front. Multi-objective evolutionary algorithms are heuristics that evolve a population of candidate solutions to find the Pareto optimal front in a single run. The selection criterion used to select individuals in the population play an important role in determining the quality of the solutions. Pareto-based algorithms use the Pareto selection criterion to evolve different parts of the solution space introducing diverse solutions, but converge slowly to the optimal front. On the other hand, non- Pareto selection Criterion (NPC) algorithms converge faster to the Pareto front, but in the process eliminate other diverse solutions. To compensate for the strengths and weaknesses of PC and NPC, hybrid frameworks such as BCE (bi-criterion evolutionary) have been proposed. In BCE, the PC and NPC algorithms evolve separately, but also co-operate by exchanging information to explore and exploit the objective space. In the literature, two well-known evolutionary algorithms, Non-dominated Sorting Genetic Algorithm II (NSGA-II) (PC) and Multi-objective Evolutionary Algorithm based on Decomposition (MOEA/D) (NPC) have been used as a case study in the BCE framework. However, the individual algorithms are computationally expensive. In this thesis, we study the parallelization of the BCE framework. NSGA-II is highly data parallel, and is well suited for single instruction multiple data architectures. MOEA/D is non-data parallel with some parts of the algorithm being sequential. Therefore, we design the parallel NSGA-II algorithm on the GPU multi-core accelerator and parallel MOEA/D algorithm on multi-core CPU machines using an island model. Using the travelling salesperson benchmark data sets we analyze the performance of the parallel hybrid algorithm quantitatively and qualitatively using metrics such as IGD scores, scalability, and speedup.February 202
Using non-traditional methodology to evaluate the influence of commercial operations on Great Slave Lake Trout, Salvelinus namaycush
Get PDFMultiple surveys have taken place on Great Slave Lake with the aim of collecting data on fish populations to achieve sustainable management, however, a lack of consistency and lake coverage from these investigations’ limits data useability. Misinterpretations of data collected in early research likely contributed to the collapse of the Lake Trout, Salvelinus namaycush, stocks shortly after the commercial fishery began. The limited abundance indices available for Lake Trout, further complicated by inconsistent management areas and recording methods, prevents the incorporation of all available data into a conventional stock assessment model. Therefore, CMSY++, the most recent version of the data-limited, surplus production model, CMSY, was applied to assess the status of Great Slave Lake Trout populations. The results generated in this assessment predict that Lake Trout stocks in all current commercially fished regions are overfished, with combined Lake Trout and Lake Whitefish, Coregonus clupeaformis, quotas above estimated Lake Trout maximum sustainable yields. My findings indicate Lake Trout commercial harvest in recent years has surpassed the estimated maximum sustainable yield for the stock in some management areas. Inferences from modeling catch-time series of varied lengths suggest ~50 years of catch data should be sufficient for reference point estimation for these Lake Trout populations, as longer time series did not decrease uncertainty. The management areas with the most commercial harvest (Areas IW & IE) reveal the greatest uncertainty associated with biomass estimates, suggesting more data is required to better understand the current state of the stocks and any increases to quotas should not occur until this is done. Conclusions of my research support those suggested over 50 years ago; Lake Trout and Lake Whitefish, should be managed through separate commercial quotas to achieve sustainable management for these populations.May 202
Microbial enzymes and major applications in the food industry: a concise review
No full textAbstract The use of enzymes in the production of food products is an ancient practice. Microbes provide several enzymes that are involved in improving the taste, texture, as well as aroma of food items, offering several benefits to the food industry. Subsequently, the ease of availability of these microbial enzymes has increased their utilization in the food industry. This cost-effectiveness and ease of commercial-scale production make enzymes ideal tools for various industrial uses. Microbial enzymes are utilized in processing food products such as those associated with the brewery, dairy and bakery industries. In addition, the nutritional value, color, aroma and texture of food products can be improved by using microbial enzymes. With the progress in technology, several novel enzymes in various applications of the food and beverages industry have been developed and demand is constantly increasing. The present review provides a comparative narrative of the applications of some of the predominating enzymes, such as phytases, lipases, lactases, pectinases, and laccases, commonly used as processing aids in the food industry. Graphical Abstrac
Research on size reduction of magnetic components in grid-connected converters
No full textThe rapid pace of electrification and adoption of renewable energy sources necessitate the development of efficient, cost-effective, and compact power electronic converters. Among the essential components in modern converters, magnetic components play a crucial role, with their size and quantity varying depending on the application, power rating, and converter topology. Reducing the size and number of magnetic components lead to higher converter efficiency, lower cost, and higher power density.
This thesis presents two distinct methods for reducing the size and quantity of magnetic components in single-phase and three-phase grid-connected converters. In single-phase converters, an innovative interleaving method is proposed, which effectively increases the power rating of a commercial Gallium Nitride (GaN)-based Power Factor Correction (PFC) converter. The proposed interleaving method along with GaN transistor and an advanced controller operating in Discontinuous Conduction Mode (DCM) lead to substantial inductor size reduction in the PFC converter and Electromagnetic Interference (EMI) filter. For three-phase converters, a novel set of topologies known as "reconfigurable filter" is introduced, minimizing the number of magnetic components. These reconfigurable filters construct LCL filters using only three inductors, a notable reduction compared to the conventional LCL filters requiring six inductors. The key components of the reconfigurable filters are a set of low-frequency bidirectional switches which lead to full utilization of existing magnetic components by changing their roles from the grid side to the converter side. The proposed topologies achieve comparable Total Harmonic Distortion (THD) performance compared to conventional LCL filters while utilizing three fewer inductors. Additionally, the reconfigurable filters suppress leakage current and offer reactive power support, making them versatile for diverse applications. The proposed topologies are applied in two different applications including PFC converters and Photovoltaic (PV) inverters.
All proposed solutions are characterized through equivalent circuits and mathematical models, accompanied by practical design guidelines. To validate the proposed methods and topologies, experimental prototypes are constructed and rigorously tested, yielding promising results. Detailed comparisons highlight the significant advancements achieved through the proposed solutions.Mitacs, Canada (Application Ref.: IT28708).
Power Integrations Inc.May 202
QTL analysis of native Fusarium head blight and deoxynivalenol resistance in ‘D8006W’/’Superior’, soft white winter wheat population
No full textAbstract
Background
Fusarium head blight (FHB), caused by Fusarium graminearum, is a major disease of wheat in North America. FHB infection causes fusarium damaged kernels (FDKs), accumulation of deoxynivalenol (DON) in the grain, and a reduction in quality and grain yield. Inheritance of FHB resistance is complex and involves multiple genes. The objective of this research was to identify QTL associated with native FHB and DON resistance in a ‘D8006W’/’Superior’, soft white winter wheat population.
Results
Phenotyping was conducted in replicated FHB field disease nurseries across multiple environments and included assessments of morphological and FHB related traits. Parental lines had moderate FHB resistance, however, the population showed transgressive segregation. A 1913.2 cM linkage map for the population was developed with SNP markers from the wheat 90 K Infinium iSelect SNP array. QTL analysis detected major FHB resistance QTL on chromosomes 2D, 4B, 5A, and 7A across multiple environments, with resistance from both parents. Trait specific unique QTL were detected on chromosomes 1A (visual traits), 5D (FDK), 6B (FDK and DON), and 7D (DON). The plant height and days to anthesis QTL on chromosome 2D coincided with Ppd-D1 and were linked with FHB traits. The plant height QTL on chromosome 4B was also linked with FHB traits; however, the Rht-B1 locus did not segregate in the population.
Conclusions
This study identified several QTL, including on chromosome 2D linked with Ppd-D1, for FHB resistance in a native winter wheat germplasm
Effective school leadership to support innovative teaching: mathematics education using the thinking classrooms framework
No full textManitoba students are struggling in mathematics. In the 2020/21 school year, 12.8% of Grade 9 students failed to earn their mathematics credit on their first attempt; this nearly triples to a 34.2% failure rate for Indigenous students (Manitoba Education and Early Childhood Learning, n.d.). Additionally, on the 2019 Pan-Canadian Assessment Program (PCAP), Grade 8 students in Manitoba had mean scores below the Canadian mean in all mathematics subdomains (O’Grady et al., 2021). Liljedahl (2016, 2021) found that students struggle to learn mathematics in traditional classrooms because teachers are planning lessons that do not require them to actively think. In response, he developed the Thinking Classrooms framework for teaching mathematics; it’s use has exploded in Kindergarten to Grade 12 classrooms in Manitoba, across Canada and around the world. While much research has been done to develop the framework and recommend effective practices for teachers, none has examined the role of school leaders who are expected to support it. This is problematic because policymakers are expending large amounts of money, time, and physical resources for teachers to create their own Thinking Classrooms while school leaders are left to muddle through. This study asks, what are the optimal practices for school leaders who want to support the mathematics instruction of teachers who are establishing Thinking Classrooms in K-12 schools? An interview-based qualitative research approach was used to learn from the experiences of teachers and school leaders in a large metropolitan school division located in Manitoba. The results are useful for school leaders who want to support their own teachers’ implementation of the Thinking Classrooms framework and improve the education of mathematics.May 202
Spatiotemporal variation in anadromous Arctic char (Salvelinus alpinus) foraging ecology and its influence on muscle pigmentation along western Hudson Bay, Nunavut, Canada
No full textClimate-induced alterations to Arctic sea ice dynamics are influencing the availability and distribution of resources, and in turn, the nutrient and energy intake of opportunistic predators across the food web. These temporal changes in local prey communities likely influence the availability of carotenoid-rich prey types, as well as the foraging ecology of opportunistic predators that forage in the marine environment, such as anadromous Arctic char (Salvelinus alpinus). Despite its socioeconomic importance across its range, anadromous Arctic char foraging ecology and its influence on muscle pigmentation, particularly in relation to sea ice dynamics, remains understudied. Here, over two years (2021, 2022) with contrasting sea ice dynamics, I investigated the foraging ecology of anadromous Arctic char and its influence on their muscle pigmentation at a southern (Rankin Inlet) and northern (Naujaat) location along western Hudson Bay using a combination of stomach contents, stable isotopes (δ¹³C and δ¹⁵N), highly branched isoprenoids, carotenoid spectrophotometry, and a standard muscle colour scale (DSM SalmoFan). Spatiotemporal variation in Arctic char diet occurred, where Rankin Inlet Arctic char generally consumed more fish and phytoplankton-based carbon sources, occupied a higher trophic position, and displayed a similar isotopic niche breadth compared to Arctic char in Naujaat. Invertebrates were higher in carotenoid concentration than fishes, and in association with a more invertebrate-based diet, Arctic char in Naujaat contained higher muscle carotenoid concentrations (e.g., astaxanthin) compared to Rankin Inlet Arctic char in 2021. In 2022, however, muscle carotenoid concentrations in Naujaat and Rankin Inlet Arctic char were more similar, as the diet of Arctic char in both locations was largely fish-based despite muscle colour remaining redder in Naujaat Arctic char. Overall, the observed plastic foraging ecology of Arctic char highlights this species' ability to adjust to inter-annual variability in environmental changes, which then impacts their muscle carotenoid concentration. Such inter-annual variation in Arctic char foraging ecology is anticipated to increase with unpredictable climate-driven environmental changes in the region, which could therefore negatively affect local resource users over the long term, resulting in socioeconomic impacts across the Arctic.Mitacs, Natural Sciences and Engineering Research Council of Canada (NSERC), Weston Family Foundation, Nunavut Wildlife Management Board, University of Manitoba, Canadian Wildlife Federation, Government of Nunavut, Fisheries and Oceans Canada (Nunavut Implementation Fund, Marine Conservation Target Fund), Crown-Indigenous Relations and Northern Affairs Canada (Indigenous Community-Based Climate Monitoring Program), and Indigenous Services Canada (Climate Change and Health Adaptation Program).May 202
Active risk management in dynamic teams of heterogeneous robots
Get PDFIn Urban Search and Rescue (USAR), hazards such as structural collapse and fire can significantly endanger robots. To mitigate these risks, it is crucial to plan task allocations that adapt to dynamic environments. Most available strategies begin with evaluating the mission in advance and formulating a static plan, which may be inflexible for unforeseen changes. This project seeks to expand our lab’s existing framework by integrating Active Risk Management (ARM) into ongoing missions. The ARM module enhances adaptability by continuously monitoring environmental hazards and initiating risk mitigation tasks.
Additionally, a novel method for detecting and escaping local minima allows robots to adjust their navigation patterns, preventing immobilization. The simulation environment now features realistic fire propagation, introducing a dynamic element that rigorously tests the effectiveness of the robots’ risk management strategies. By incorporating these advancements, we aim to increase mission success rates and significantly reduce robot damage in challenging USAR scenarios.October 202