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Investigating Metabolic And Inflammatory Relationships In Two Distinct Models Of Right-Sided Cardiac Stress
No full textThis thesis summarizes data generated from two distinct models with unrelated underlying etiology that both implicate metabolic- and inflammatory-mediated adaptations in right-sided cardiac stress.
The first model, Duchenne muscular dystrophy (DMD), is a neuromuscular disease caused by mutations in the X-linked DMD gene that encodes the sub-sarcolemmal protein, dystrophin. While current standards of care –glucocorticoid administration and gene-editing therapies – provide promise for skeletal muscle impairments, the effects of these interventions on dystrophic cardiomyopathy are unclear. The purpose of this thesis was to characterize chamber-specific remodeling in young D2.B10-DMDmdx/2J (D2.mdx) mice, while concurrently exploring if an adiponectin peptidomimetic (ALY688) could alleviate underlying chamber-specific pathology.
Our results demonstrated that right ventricular (RV) fibrosis and cardiomyocyte hypertrophy in 4-week-old D2.mdx mice were related to lower mitochondrial respiration and increased complex I-stimulated mitochondrial H2O2. ALY688 prevented RV fibrosis and cardiomyocyte hypertrophy, concurrent with macrophage sub-population shifts towards an anti-inflammatory phenotype. Our findings identified that the dystrophic heart is heterogeneously affected, while ALY688 represents a viable intervention aimed at addressing secondary contributors to dystrophic cardiac remodeling.
The second model, on-pump coronary artery bypass grafting (CABG) surgery, is a common intervention for treatment of coronary artery disease. Key to this surgery is infusion of cardioplegia, which temporarily arrests the heart so surgeons can anastomose grafts around occluded coronary arteries while blood supply is maintained by cardiopulmonary bypass. The combination of ischemia and reperfusion remains a precipitator of post-operative complications. To date, repeated-measures mitochondrial stress responses associated with CABG have never been explored in a study design that compares right atrial appendage (RAA) samples from the same patient at multiple time-points.
Therefore, the purpose of this study was to investigate if post-CABG RAA exhibited alterations to mitochondrial stress responses (perturbed mitochondrial substrate-specific respiration and reactive oxygen species (ROS)-mediated protein adaptations) that correlated with patient discharge times.
Preliminary findings demonstrated that CABG is associated with increased fatty acid-supported respiration on the post-CABG RAA. It is unknown if this is a protective mechanism or a detrimental mitochondrial stress response. Correlative statistics suggest that the increase in fatty acid-supported respiration and ROS-mediated adaptations do not improve patient discharge times
Role(s) Of Pannexin1A/B In The Physiology Of The Zebrafish Visual System
No full textPanx1 proteins are glycosylated integral membrane channels with unique conduction properties, functioning as an ATP channel and non-selective ion channel in different physiological pathways. In zebrafish, the mammalian Panx1 ohnologues, Panx1a and Panx1b, have distinct tissue expression patterns. We previously demonstrated that in the retina, Panx1a is localized in the horizontal cell layer and the ON/OFF ganglion cell layer, while Panx1b protein is present in the horizontal cell layer, ganglion cell layer, and in the end-feet of the Muller glia astrocytes. Here we investigated the optic flow response in the Panx1a-/- and Panx1b-/- 6dpf larvae utilizing molecular, systems, and behavioral assays. The RNA-seq analysis revealed broad regulation of genes involved in axon guidance, retinal axon guidance, astrocytes, axons, dendrites, and synapse, confirmed by RT-qPCR in the 3dpf and 6dpf Panx1a-/- and Panx1b-/-. We demonstrate that Panx1a-/- and Panx1b-/- display an inability to make a leftward and rightward directional motion in low light contrast conditions when exposed to the left and right moving gratings. We also show how the strategic localization of Panx1a and Panx1b in the habenula region modulates visually guided behavior. Lastly, Panx1a-/- and Panx1b-/- demonstrate the inability to generate functional saccades and display ocular motor deficiencies linked to potential neurological disorders. These findings suggest that Panx1 modulates the axonal growth in axon guidance pathfinding and together are interconnected to the habenula region, leading to synaptic plasticity of the retinal neural circuitry, and regulating visually guided locomotion in the zebrafish larvae
Intimate Partners' Awareness of and Responses to Self-Injurious Thoughts and Behaviours in People with Borderline Personality Disorders: A Mixed-Methods Descriptive Study
No full textIntimate relationship dysfunction is characteristic of borderline personality disorder (BPD), and partners’ behaviours may exacerbate or ameliorate self-injury in BPD. Therefore, this study investigated partners’ awareness of people with BPD’s self-injury, how they find out about self-injury, their responses to self-injury, and their self-evaluated helpfulness. To address these aims, 15 people with BPD and their 15 partners reported on the presence or absence of self-injury for 30 days; partners also reported how they found out about self-injury for 30 days and completed semi-structured interviews about a recent response to self-injury and their self-evaluated helpfulness. Partners were aware of 40% of self-injury, and 66.7% found out about self-injury because people with BPD disclosed it. Qualitatively, most partners responded to self-injury by soothing, protecting, and/or problem solving for people with BPD. Most partners observed mixed or negative reactions to their efforts, and perhaps consequently, some felt lost about how helpful they were
The Relative Importance Of Microclimatic Heterogeneity On Plant And Animal Communities In Deserts Of Southern California, U.S.A
No full textThis dissertation examines the intricate relationships between facilitation, environmental heterogeneity, and artificial habitat constructions in arid ecosystems, focusing on plant-animal and plant-plant interactions. By leveraging ecological principles, it explores the role of foundation plant species like Ephedra californica and Larrea tridentata in fostering ecosystem resilience and biodiversity under adverse conditions due to climate change, land use, and desertification.
The study starts with an overview of facilitation theory, highlighting its importance in mitigating the negative effects of abiotic stressors in arid and semi-arid regions. It highlights the Stress Gradient Hypothesis (SGH) as a framework for understanding how competitive interactions can shift towards facilitation under harsh conditions, thus promoting the survival of diverse flora and fauna. The dissertation then delves into environmental heterogeneity, explaining its complex influence on ecosystem dynamics, species composition, and microclimatic regulation.
Chapter 2 provides a detailed analysis of camera trapping techniques, offering optimal sampling design strategies for accurately estimating vertebrate abundance and richness. Chapter 3 examines the effects of artificial canopies on microclimate regulation. This chapter evaluates various eco-friendly fabrics, such as natural burlap, cotton, and nursery seedling fabric, in buffering microclimate through lab experiments measuring understory temperature, relative humidity, and radiation.
Chapters 4 and 5 investigate how climatic variations and vegetation structure contribute to spatial and environmental heterogeneity, shaping flora and fauna diversity and abundance. A key aspect of the study is evaluating the effectiveness of artificial habitat construction as a conservation and restoration strategy in arid landscapes. Field experiments assess the microclimatic buffering capabilities of artificial shelters compared to natural vegetation in supporting vertebrate populations amid desertification in the Southwestern U.S.A.
Overall, this dissertation enhances our understanding of the complex interplay between facilitation, environmental heterogeneity, and habitat modification in arid ecosystems. By uncovering the mechanisms behind these ecological processes, it provides valuable insights for conservation, management, and restoration efforts in regions vulnerable to anthropogenic disturbances and climate change
A Solution for Scale Ambiguity in Generative Novel View Synthesis
No full textGenerative Novel View Synthesis (GNVS) involves generating plausible unseen views of a scene given an initial view and the relative camera motion between the input and target views using generative models. A key limitation of current generative methods lies in their susceptibility to scale ambiguity, an inherent challenge in multi-view datasets caused by the use of monocular techniques to estimate camera positions from uncalibrated video frames. In this work, we present a novel approach to tackle this scale ambiguity in multi-view GNVS by optimizing the scales as parameters in an end-to-end fashion. We also introduce Sample Flow Consistency (SFC), a novel metric designed to assess scale consistency across samples with the same camera motion. Through various experiments, we demonstrate our approach yields improvements in terms of SFC, providing more consistent and reliable novel view synthesis
Application of GNSS Precise Point Positioning to Low-Cost Hardware for cm-level Positioning
No full textPrecise Point Positioning (PPP) offers high-precision GNSS positioning solutions. The advent of low-cost hardware provides an affordable alternative to costly geodetic-grade hardware, broadening the accessibility of high-precision positioning across many applications. However, this hardware produces measurements with higher noise levels, reduced multipath suppression, and lower carrier-to-noise density ratios (C/N0), restricting its ability to achieve cm-level accuracy. This study addresses these limitations by developing a novel C/N0-based empirical observation weighting model to accompany the signal characteristics of low-cost hardware. This model enhances positioning accuracy by emphasizing high-quality signals above a nominal C/N0 threshold and down-weighting observations below it. The proposed model reduces float to carrier-phase integer ambiguity resolution (fixed) convergence time by 71% for 5 cm and 38% for 2.5 cm horizontal error thresholds for the static dataset tested, demonstrating the potential of low-cost GNSS devices as viable, high-precision positioning solutions
Capital as Power in the 21st Century. A Conversation
No full textOn December 3, 2024, Michael Hudson met with capital-as-power researchers Jonathan Nitzan, Tim Di Muzio and Blair Fix to discuss the intersections between their two lines of research.
YouTube video: https://www.youtube.com/watch?v=tBOU4xBg2p
Design, Development, and Validation of an End-User Photo-Thermal Sensing Platform for Rapid Detection and Quantification of Analytes in Fluidic Samples
No full textThe ability to detect the presence of specific analytes and quantify their titers in fluidic samples is essential in many industries, spanning from food industries to law enforcement to healthcare and beyond. The existing technologies used for this purpose require the use of specialty equipment by trained professionals in a laboratory setting to function (e.g., mass spectrometry or ELISA) which greatly increases the cost and time taken to receive actionable results. Portable and inexpensive tests exist – Lateral Flow Immunoassays – however these tests are only qualitative and frequently have an inferior limit of detection. To date, several sensing devices have been designed to interrogate these LFIAs and decrease their limit of detection, however, these devices are often prohibitively expensive. This thesis outlines attempts to design and validate a sensing platform which could inexpensively enhance the limit of detection of LFIAs.The prototype is then validated through both lab-based and human experiments
A Safety Analysis of Left-Turning Maneuvers for Long-Combination Vehicles
No full textA growing number of goods are shipped in Ontario using long-combination vehicles (LCVs). LCVs can significantly increase the amount of cargo carried per shipment, while reducing shipping costs and environmental impacts of freight road travel. Questions remain regarding their safety due to their larger size and wider maneuvering. This thesis furthers our understanding of LCV safety considerations in last-mile areas during left-turning maneuvers by focusing on conflicts with infrastructure and road users. Intersections are selected along Peel Region’s Strategic Goods Movement Network and left-turning swept path analyses are performed using AutoTurn. A microsimulation of the intersections is developed, where the existing network is modeled in Vissim while LCVs are added as potential road users. The Surrogate Safety Assessment Model is then used to analyze the microsimulation results pertaining to potential collisions. It was found that existing last-mile infrastructure is ill-equipped to accommodate LCVs and requires adjustments for future LCV use
Investigating The Effect Of Chronic Muscle Use And Disuse On Innate Immune Signaling In Skeletal Muscle
No full textSkeletal muscle health is highly dependent on the intricate mitochondrial reticulum that exhibits high levels of adaptability. It is now recognized that mitochondrial perturbations can activate innate immune pathways, such as the NLRP3 inflammasome complex, by augmenting the response against damage-associated molecular patterns (DAMPs). The objective of this study was to investigate how various metabolic conditions affect innate immune activation and mitochondrial health within skeletal muscle, which has not been fully elucidated. To investigate this, we assessed innate immune signaling pathways and mitochondrial parameters within a model of muscle denervation and an aging model combined with endurance training. Our results suggest that NLRP3 inflammasome signaling is responsive to alterations in skeletal muscle activity and can be attenuated with chronic endurance training. Furthermore, we highlight a differential response to exercise with aged muscle in innate immune signaling. This work aims to further the understanding of innate immune signaling pathways within skeletal muscle, which can potentially highlight therapeutic targets to regulate its activation under divergent metabolic conditions