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    Investigating the therapeutic potential of REV-ERB⍺ activation in chronic inflammatory diseases

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    Metabolic-associated steatohepatitis (MASH) is a metabolic disease of the liver, that manifests itself as steatohepatitis, inflammation, and fibrosis. It has the potential to progress to cirrhosis and hepatocellular carcinoma if uncontrolled. Currently, there is no effective treatment strategy except lifestyle changes. It is imperative to develop therapeutics against MASH and alleviate the leading cause of liver transplants across the world. We and others have shown that nuclear receptor REV-ERB plays a significant protective role in liver biology by acting as a transcriptional repressor of important genes involved in metabolism, inflammation, and fibrosis. While we have shown that in-vivo administration of REV-ERB agonist SR9009 is able to alleviate symptoms of MASH such as inflammation and fibrosis, we are yet to find out its mechanism of action. Additionally, SR9009 has its limitations in terms of solubility and efficacy. In this dissertation, we utilize a relatively novel REV-ERB agonist STL1267 and explore its efficacy in the treatment of MASH. We also explore its mechanism of action using in-vitro and in-vivo mouse models. We found that STL1267 is more effective in treating MASH, with increased reduction in triglycerides, inflammation, and fibrosis. We were able to show that REV-ERB agonism acts via metabolically reprogramming energy metabolism in cells associated with MASH. It reduces mitochondrial metabolism, and alleviates metabolic stress, reducing the further downstream effects such as oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis in cells such as hepatocytes, stellate cells, and macrophages

    Quantifying the legacy of coal combustion products in riverine sediments

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    Coal fired power plants (CFPPs) produce much of the world’s energy and generate large quantities of coal combustion products (CCPs), including organic material (OM), fly ash, bottom ash, spheroidal carbonaceous particles (SCPs) and metals, much of which is stored near CFPPs. Despite projected closures of CFPPs, these waste products will persist and can potentially impact environments. Here, we develop a new method for SCP enumeration by analyzing 14 riverine sediment sites and then use bootstrapping techniques to quantify measurement precision as a function of subsample number. We recommend the enumeration of SCPs in sets of at least 10 subsamples per site to maximize precision and minimize error. Next, using SCP, toxic metal, and OM concentrations, we explore the differences in CFPP contamination near an active and a legacy (closed) plant. We find that for our study sites, SCPs are a better proxy for CCP environmental impacts than toxic metal or OM concentrations. SCP concentrations are highest near the active CFPP but also are present near the legacy CFPP. Even after coal combustion ceases and impoundments are closed, CCPs persist in the environment

    Knowledge, Perception, and Practice of TIC by Pediatric SLPs Employed in Medical Settings

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    Purpose: The purpose of this study is to investigate the knowledge and practice of trauma informed care (TIC) within a sample population of SLPs who work in medical settings with pediatric patients. This survey also evaluated the self-perception of the participant’s competency and comfort when implementing TIC practices and values, as well as perceived barriers to implementation. Method: Data was collected through an anonymous 73-item, web-based survey. Eighty-five participants initiated the survey, and 50 participants met inclusion criteria and completed the survey. Survey questions addressed: (a) Background/demographic information (b) Graduate or professional training in TIC, and (c) Knowledge, opinions, and practice of TIC. Knowledge and Practice of TIC was queried using the Trauma Informed Care Providers Survey (Kassam-Adams et al., 2015). Results: The findings underscore knowledge of some areas of TIC and gaps in others, moderate perceived competency, and implementation of TIC. Lack of training was noted as a significant barrier. SLPs who received continuing education (CE) on TIC, reported significantly higher perceived competency. No significant group differences were found between those who attended CE opportunities and knowledge of TIC. Conclusions: This study reveals the need for increased training and awareness about TIC within the SLP profession. Training and implementation of TIC principles may improve provider-patient relationships, decrease burnout, minimize potential harm, and raise the standard of care for SLPs in the medical setting. Training should specifically address signs of a traumatic stress response and the role of resilience

    Mortality components for two Micropterus spp. in a Southeastern reservoir: a high-value reward and radio telemetry approach.

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    For black bass species (Micropterus spp.) post-release mortality rates are higher for tournaments than non-tournaments and may be a significant component of total fishing mortality. On Neely Henry Reservoir in Alabama there is concern that catch-and-release may be a substantial component of black bass mortality. In particular perceived high effort tournament angling could be causing high fishing mortality. To address this concern, I used a combined high-value reward and radio telemetry approach to partition mortality for Largemouth (Micropterus nigricans) and Alabama Bass (Micropterus henshalli) into harvest, non-tournament catch-and-release, tournament, and natural mortality. Anglers were incentivized by high value rewards to report angling captures, and manual telemetry searches were used to ascertain the survival status of fish. I present an analytical approach that builds on previous studies to incorporate misclassification of survival from radio tags, tag shedding, tagging mortality, and angler non-reporting. I found the relative magnitude of catch-and-release fishing mortality as a component of total mortality was 0.17 and 0.03 for Alabama and Largemouth Bass, respectively. Catch-and-release angling contributed 52% and 20% of total fishing mortality for Alabama Bass and Largemouth Bass respectively, indicating that different black bass species are subject to differential effects of recreational angling. I found the relative magnitude of catch-and-release fishing mortality as a component of total fishing mortality is considerable for black bass species in Neely Henry Reservoir. Results from this study are applicable to other freshwater sport fisheries and indicate that importance of incorperating catch-and-release mortality as a component of total when volunraty release is high

    Geometric Representation Learning on Molecular Graphs

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    Graphs as a type of data structure have recently attracted significant attention. Representation learning of geometric graphs has achieved great success in many fields including molecular, social, and financial networks. It is natural to present proteins as graphs in which nodes represent the residues and edges represent the pairwise interactions between residues. However, 3D protein structures have rarely been studied as graphs directly. The challenges include: 1) Proteins are complex macromolecules composed of thousands of atoms making them much harder to model than micro-molecules. 2) Capturing the long range pairwise relations for protein structure modeling remains under-explored. 3) Few studies have focused on learning the different attributes of proteins together. 4) Existing graph neural networks (GNNs) have limitations in capturing complex multi-level structural information and handling variable sizes of molecular structures. In this dissertation, we propose four geometric representation learning frameworks to address the above challenges under different scenarios. First, we introduce the Protein Graph-GNN (PG-GNN) architecture for protein backbone structure modeling, which utilizes geometric graph convolution blocks to generate distance geometric graph representations and can handle variable sizes of protein graphs dynamically. This gives a significant advantage because this network opens a new path from sequence to structure. Second, we develop the Attention-based Protein-drug Interaction Prediction (APIP) framework for interpretable protein-ligand interface prediction, which handles different input types separately and models long-range dependencies in protein sequences. Third, we present the Explainable framework for drug-target Interaction prediction (EIR), which incorporates both intrinsic and extrinsic information to enhance interpretability and accuracy in drug screening. Finally, we propose the Subgraph Aggregation Module Network (SAMNet), a provably geometric lossless encoding and rotation equivariant network for molecular representation learning, which captures complex geometry across spatial dimensions using a subgraph sampling policy and a drop-in geometric Subgraph Aggregation Module (SAM). We conducted extensive experiments on benchmark datasets and demonstrated the effectiveness of the proposed methods for in silico structural biology and rational drug discovery, and showcased their ability to address the limitations of existing GNNs in molecular representation learning. By developing these novel approaches, we contribute to advancing the field of life science and pave the way for more accurate, interpretable, and generalizable machine learning models in protein structure prediction, drug discovery, and molecular representation learning

    Principal Preparation Programs: Addressing Aspiring School Leader Well-Being

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    The National Educational Leadership Preparation Program (NELP, 2018) standards require that effective school leaders not only promote the well-being of students but also promote the well-being of the adults in the building, which includes the administrators themselves. Aspiring leader well-being is a much-neglected aspect of educational leadership preparation. The purpose of this sequential explanatory mixed-methods study was to use a positive psychology framework to address a gap in the literature and to inquire about the extent to which principal preparation programs were addressing well-being and what, if any, strategies or curricula were in place in UCEA-member institution educational leadership programs in 2023-2024 to promote the well-being of aspiring school leaders. The findings suggest that principal preparation programs need an intentional approach to well-being in their curricula and explicit ways to integrate well-being awareness and strategies into their programs that will assist future school leaders in their resilience and the sustainability and longevity of their careers using the structures and processes they already have in place

    Understanding the Production Risk of Conservation Tillage Practices

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    This study examines the effects of different degrees of conservation tillage methods on agricultural production losses. To accomplish this objective, we employ a unique county-level panel dataset containing data on conservation tillage acreage, crop insurance losses, and weather variables. The data encompasses corn and soybean production in the states of Iowa and Illinois spanning from 2005 to 2019. We employ the traditional fixed effect econometric model and conducted several robustness tests in the empirical research utilizing disaggregated monthly weather variables and extended duration aggregated weather variables. Evidence indicates that counties with elevated no-till practices tend to have greater overall farm losses, whereas counties with increased reduced till practices are likely to incur lower overall farm losses. Overall, our findings indicate that reduced tillage may mitigate agricultural output risk and serve as an effective climate change adaptation strategy in US agriculture. These results provide insights for policymakers aiming to consider integrating conservation tillage into risk management programs or subsidies more effectively by differentiating subsidies by tillage types

    Evaluating Pesticide Strategies and Spray Technology Across Diverse Southern U.S. Row Crop Systems

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    Effective weed management and pesticide application are crucial to achieving optimal productivity of economically important crops in the southern U.S., such as corn (Zea mays), soybean (Glycine max), and cotton (Gossypium species). This dissertation evaluates strategies to optimize herbicide efficacy and application techniques while integrating technologies to address new challenges in weed management and crop protection. Gramineous weeds, such as crabgrass (Digitaria sanguinalis) and Texas panicum (Panicum texanum), pose significant challenges in crop systems, especially those without herbicide-tolerant traits like peanuts. A field study evaluated the efficacy of herbicide options targeting these species at two critical timings: preemergence and postemergence. Preemergence herbicide applications provided up to 94% of crabgrass control, while Texas panicum was more challenging to control. Pyroxasulfone plus carfentrazone provided consistently superior control for Texas panicum, as confirmed through normalized difference vegetation index (NDVI) and biomass measurements. Postemergence applications showed that application timing significantly influences the level of control. Early applications proved most effective, particularly for the Texas panicum, with glyphosate maintaining efficacy even at lower rates across both growth stages tested. Overall, these results highlight the importance of timely herbicide application for effectively managing a broad range of gramineous weeds. Volunteer peanuts in cotton-peanut rotations have become a challenge as they can act as weeds and reservoirs for disease and insects. Isoxaflutole, applied alone or in a mixture with dicamba and fomesafen, provided high levels of volunteer peanut control, with the greatest levels of activity observed at higher rates. Due to isoxaflutole residual activity, it can be highly effective against large-seeded broadleaf weeds. It offers a promising solution for managing volunteer peanut control in cotton with isoxaflutole-tolerant traits. New approaches to applying pesticides, including sprayer unmanned aerial vehicles (UAVs), raise concern regarding potential crop injury due to the ultra-low volume used in this application compared to traditional practices. This study aimed to evaluate soybean injury from low-volume applications by UAV and ground sprayer applications at different spray volumes. Overall, higher spray volumes correlated to higher injury, likely due to greater chemical coverage and distribution on soybean leaves. Significant differences in soybean heights were observed 7 days after treatment (DAT), with the lowest height recorded in treatments where fomesafen was applied via ground sprayer at a spray volume of 47 L ha-1. In conclusion, spray applications with ultra-low volume did not result in more injury than traditional application methods. However, questions regarding weed control efficacy remain. In tall crops like corn, mid-season aerial applications with UAVs were compared with fixed-wing airplanes regarding the assessment of spray deposition and canopy penetration. UAVs gave an equal or better performance, while propeller downdraft enhanced canopy penetration. When drift-reducing agents (DRAs) were added to the tank mixture, deposition under windy conditions was improved, thus supporting the feasibility of UAVs as an alternative to conventional methods in applying fungicides in tassel-stage corn. Overall, these studies provide important insights to enhance weed management and a comprehensive use of new application technologies to improve crop protection targeting specific challenges encountered by growers in southern U.S

    The Mechanistic-Empirical Design Guide (MEPDG): An Analysis of Different Level Inputs for Alabama Pavement Surface Mixtures

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    Since the beginning of pavement design, there have been several methods that can aid in determining and estimating a pavement’s construction, rehabilitation, and end of life. Current design methods include but aren’t restricted to empirical, limiting shear-failure, limiting deflection, and regression methodologies. A newer method was introduced that combines observed destructive and nondestructive pavement performances and reconciles those results to identify physical distresses within the pavement structure. This approach can be used more accurately during pavement design due to the addition of pavement performance simulations and calibrations. These design considerations can give a better understanding of how pavements deteriorate over time and could eventually lead to advancements in new design technologies, which will aid in the mitigation of future distresses when a new road is being constructed or if an existing road needs rehabilitation. The results of various pavement performance tests can be modified and used as inputs into design guides, creating better design criteria in comparison to previous methods. The collection of information from locally gathered materials, climactic data, and performance calibrations can be utilized in creating more accurate pavement designs, given the moniker of the Mechanistic-Empirical Design Guide (MEPDG). This thesis aims to highlight the importance of MEPDG by collecting respective data that would be used as Level -1 and -2 inputs for pavement design while also comparing the sensitivity of different mix test results throughout the state of Alabama. Asphalt mixes were tested in accordance with ALDOT and AASHTO methodologies, where results from different tests correlated with their susceptibilities to mixture rutting, mixture stiffness, and creep compliance and strength. Each mix’s data was compared with one another to determine errors, similarities, or differences between mix designs while also utilizing transfer functions within the modeling program of the Pavement Mechanistic-Empirical Design (PMED) to determine and judge the accuracy of MEPDG against previous accumulated state designs. Between 2021 and 2022, nine asphalt mix designs from five regions in Alabama were distributed to the National Center for Asphalt Technology (NCAT) for performance testing. The extracted/recovered binders were tested with the Dynamic Shear Rheometer (DSR), Bending Beam Rheometer (BBR), and Rotational Viscometer (RV) to determine the Superpave Performance grade (PG), Delta Tc (ΔTc), and viscosity. The binders were also tested with the MSCR test per AASHTO T 350 for evaluating elastic response and rutting resistance; the LAS test per AASHTO T 391 for evaluating fatigue resistance; and the Frequency Sweep test followed by master-curve analysis for evaluating ductility and block cracking resistance. Mixture results were taken and analyzed from flow number (FN) or repeated load permanent deformation (RLPD), dynamic modulus (E*), and indirect tension (IDT) testing, while mix verification was performed to accurately record key mechanical properties that were later used in MEPDG (performance grade, complex modulus, gradation, specific gravities, aggregate and binder content verifications). These results showed that there was overall less discrepancy between Level-3, and combined Level -1 and -2 designs, when the distresses that were focused on were more driven to accommodate problems that were associated with high temperature plus increased loading time design potentials. As a result, there are more discrepancies in the designs when cold temperature-controlled distresses are associated

    Mitigating Salinity Stress in Red Kale (Brassica napus L. var. Pabularia ‘KX-1’) Through Split-root: Implications for Brackish Water Aquaponics

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    Brackish water aquaponics is a promising approach to expand the scope of aquaculture-hydroponics integration. However, progress on brackish water aquaponics is limited due to low salinity tolerance of most high-value vegetable crops. Salinity can significantly affect plant growth by reducing plant height, decreasing leaf number and leaf size, leading to early leaf senescence, and decreasing biomass accumulation in salt-sensitive plant species. Additionally, salinity can negatively impact plant physiological performance, resulting in reduced stomatal conductance, lower CO2 assimilation, reduced photosynthetic activity, and ultimately lower plant productivity. To address this limitation in brackish water aquaponics systems, two studies were conducted to investigate the effectiveness of split-root system in deep-water culture (DWC) hydroponics system to mitigate salinity effects on red kale (Brassica napus L. var. pabularia). The focus of the first study was to evaluate the effect of increasing salinity levels (0, 3, 6, and 9 g L-1 or ppt) on red kale growth and physiology in whole-root and split-root systems. Results indicated that red kale plants grown in split-root system had a higher growth index than whole-root system when compared to the control treatment (0 ppt) in each condition. Stomatal conductance was similar in split-root system with increasing salinity level but was greatly decreased in the whole-root system as salinity level increased. The second study evaluated the effect of brackish water aquaculture effluents on the growth and physiology of red kale in two split-root systems: homogeneous and heterogeneous. In homogeneous split-root system, both parts of the plant root system received the same treatment, while in the heterogeneous system, one part was treated and the other exposed to clear water. Treatments included hydroponic solution containing 0 ppt salinity, saltwater-based hydroponics at 11 ppt, and shrimp effluents at 14 ppt. Significant interactions were found between split-root systems (conditions) and treatments in kale growth traits including height, leaf number, size index, and shoot fresh and dry weights. The heterogeneous split-root system showed positive effects on mitigating salinity stress on red kale growth, compared to the homogeneous split-root system. Plants treated with shrimp effluents showed lower stress levels, evidenced by improved leaf stomatal conductance compared to saltwater-based hydroponic in split-root system. The split-root system demonstrated in this thesis under the DWC system offers a practical solution to mitigate salinity effects on high-value vegetable crops cultivated with brackish water aquaculture effluents. Further research can explore and refine split-root systems for commercial application in brackish water aquaponics systems

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