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Nutrient Utilization and Regulation in Retinal Pigment Epithelium
No full textPurpose: The retinal pigment epithelium (RPE) plays a critical role in maintaining vision by performing essential functions including visual cycle processing, nutrient transport, protein synthesis, protection against oxidative stress, cytokine secretion, and phagocytosis of outer segments. RPE dysfunction can cause photoreceptor cell death in inherited retinal degeneration and age-related retinal degeneration (AMD), resulting in blindness. RPE relies on its robust mitochondrial metabolism to support its multifaceted functions. However, it remains unclear how healthy RPE mitochondria fuel their metabolism and how substrate utilization is impaired in diseased RPE.
Nicotinamide N-methyl transferase, an enzyme that methylates nicotinamide into 1-methyl nicotinamide (1-MNAM) is a master regulator of mitochondrial metabolism. Transcriptomics data show that NNMT is highly expressed in RPE, and its expression is further upregulated in RPE from patients with age-related macular degeneration (AMD). A gap in knowledge remains regarding how NNMT regulates RPE substrate utilization and mitochondrial metabolism in RPE. The purpose of this work is to comprehensively evaluate nutrient utilization in healthy and diseased RPE and determine the role of NNMT in RPE metabolism. The central hypothesis is that healthy human RPE will have a high metabolic flexibility in nutrient utilization which will be disrupted in diseased RPE. NNMT is expressed in RPE to regulate its unique metabolism, but its excessive activity will contribute to metabolic changes in aging and AMD.
Methods and Results: A novel approach was developed using Biolog Phenotype Microarray Assays to screen substrate utilization in human RPE cells. Five human RPE cells were used for this substrate screening, including dedifferentiated fetal RPE (fRPE), induced pluripotent stem cell-derived RPE (iPSC RPE), Sorsby Fundus dystrophy (SFD) patient-derived iPSC RPE, CRISPR-corrected isogenic SFD (cSFD) iPSC RPE, and ARPE-19 cell lines. Some changes were further validated with stable isotope tracing using mass spectrometry. Differentiated fRPE and healthy iPSC RPE cells could use up to 51 nutrients. However, when dedifferentiated, fRPE used far fewer nutrients, primarily sugar and glutamine-related amino acids. SFD RPE can use 37 nutrients; however, compared to cSFD RPE and healthy iPSC RPE, they were unable to use lactate, some TCA cycle intermediates, and short-chain fatty acids. Nonetheless, they showed increased use of branched-chain amino acids (BCAAs) and BCAA-containing dipeptides. Dedifferentiated ARPE-19 cells grown in traditional culture media were incapable of utilizing lactate and ketone bodies. In contrast, nicotinamide supplementation promotes differentiation toward an epithelial phenotype, restoring the ability to use these nutrients.
NNMT expression was quantified by quantitative PCR and immunoblot. Human RPE cells, isolated mouse retina, and mouse RPE were incubated with deuterium nicotinamide to trace NAD synthesis and degradation. Mitochondrial oxygen consumption was measured using the Agilent Seahorse assay. Pharmacological inhibitors and constructs packaged in lentivirus or adeno-associated virus (AAV) were used for loss or gain of function studies. NNMT expression and activity were limited to the RPE but almost absent in the retina. RPE contained more 1-MNAM, the product of NNMT, than any other tissues. 1-MNAM was actively exported by the RPE to the retina. The inhibition of NNMT inhibited mitochondrial respiration and disrupted RPE nutrient utilization. Finally, NNMT was upregulated in aged RPE and RPE from AMD patients, and excessive NNMT activity impaired RPE morphology.
Conclusion: Healthy RPE cells have high flexibility in using different nutrients because of their epithelial phenotype. SFD RPE cells have reduced metabolic flexibility, relying on the oxidation of BCAAs. Our findings highlight the important roles of nutrient availability and use in RPE differentiation and diseases. NNMT is enriched in RPE, and its optimal expression is crucial for RPE nutrient utilization, metabolism, and morphology. Excessive NNMT activity in RPE may underlie pathology in aging and AMD
Design and Simulation of an AI-Powered Autonomous Quadrotor Framework for Search and Rescue Operations
No full textUnmanned aerial vehicles (UAVs), particularly quadrotor platforms, have proven to be indispensable tools for search and rescue (SAR) teams due to their maneuverability, rapid deployment, and affordable operation. The current SAR use cases of quadrotors span from aerial surveillance to mission planning and strategic deliveries. However, most SAR applications remain passive or semi-autonomous, such that they rely on human-operated control or data assessment. Advancements in autonomous control strategies bring about a future where a single SAR operator can program and deploy several UAVs. This thesis details the development and simulation of a fully autonomous, AI-powered quadrotor framework capable of detecting missing persons, navigating toward them, and dynamically avoiding obstacles within a realistic search environment. The autonomous system developed is platform independent, mission-driven, and requires no human control between deployment and SAR recovery. The simulation environment was constructed in Unreal Engine 5 leveraging a high-resolution terrain model. The mesh for the model landscape was generated using QL2 United States Geological Survey (USGS) LiDAR point clouds. The quadrotor model is controlled through MATLAB/Simulink code via co-simulation plugins that link the two software suites. The proposed UAV framework has three core subsystems for mission success: dynamic 3D Dubins path planning, active potential field obstacle avoidance, and onboard computer vision guidance. The performance of the system was evaluated by comparing the results of ten search scenarios. In simulations with a Full HD resolution camera and no line-of-sight occlusion, the UAV regularly detected ground targets at a Euclidean distance of over 30 meters while flying at an average mission speed of 3.9 meters per second. In an open terrain mission, 10 seconds from takeoff, the system was able to autonomously avoid two trees and identify a target located at a distance of over 78 meters. The framework was constructed using modular architecture: the computer vision engine, sensor models, and control logic are all independently interchangeable creating several opportunities for unique future search and rescue missions. This architecture enables a single operator to deploy and monitor multiple UAVs from a singular ground station significantly enhancing the scalability and effectiveness of searching operations
Enhancing Pillar Stability Assessment in Underground Limestone Mines Using LaModel: Integrating Empirical Strength Equations for Improved Ground Control
No full textUnderground stone mining accounts for approximately 21% of all underground mining operations in the United States, with more than 2,000 workers employed in this sector as of 2019. Ground control failures, particularly those involving massive pillar collapses and roof falls, pose significant safety hazards, contributing to 40% of fatalities and 15% of lost workdays since 2006. Several massive pillar collapses have occurred in active limestone mines from 2015 to 2021, and a fatal incident was reported in January 2022 in a mine operating within the Loyalhanna formation. Given these risks, accurate stability assessment tools are essential for improving mine safety.
The room-and-pillar mining method is predominantly used in underground stone mines, requiring careful design and monitoring of pillars throughout a mine\u27s lifespan to mitigate ground control hazards. In the U.S., empirical pillar strength equations and the S-Pillar program were developed to assist in pillar stability design. While the S-Pillar software evaluates pillar stability by calculating the safety factor based on empirical equations, it assumes uniform overburden loading. It is only valid for regularly sized pillars, limiting its effectiveness for complex mine geometries and variable topographies.
LaModel, a displacement-discontinuity boundary element method software traditionally used in coal mining, has recently been applied to stress analysis in stone mines. This research aims to investigate LaModel\u27s applicability further.
A case study of a benched pillar collapse incident is analyzed using LaModel, incorporating the effects of load transfer mechanisms and stress redistribution assessments under real-world mining conditions. Once the model is validated, parametric studies are conducted, including the width-to-height ratio difference, the collapse of a single pillar with stress propagation, lamination thickness, and width reduction due to spalling, to explore these parameters. In the case study of single pillar collapse, the results showed a stress transfer effect, with an average reduction of approximately 9% in the safety factor in adjacent pillars. This finding highlights the dependency of pillar stability, where the collapse of one pillar can compromise the structural stability of the surrounding pillars. The research also explored how varying lamination thickness affects stress distribution within materials. Results indicate that thinner laminations led to increased localized stress concentrations.
And increased the tendency of structural pillars to failure. On the other hand, a thicker lamination correlated with a more uniform distribution of stress, ultimately improving the overall stability of the structure. Additionally, a 10% and 20% reduction in pillar width due to spalling resulted in corresponding strength reductions of 3.1% and 6.48%. While a decrease in strength was observed, no significant increase in stress was found in the adjacent pillars, possibly due to the high elastic modulus of limestone. However, gradual spalling over time may lead to long-term weakening of the pillar system, making early detection and prevention crucial. Overall, the results show LaModel\u27s applicability for stone mining and offer improved methodologies for pillar design.
The second phase of the study integrates mine map layouts with high-resolution Light Detection and Ranging (LIDAR) scans to improve pillar stability assessment. A combination of software tools, AutoCAD, AutoCAD ReCap Pro, CloudCompare, and Discontinuity Set Extractor (DSE), was utilized to process and analyze point cloud data. By overlaying 2D mine maps with 3D LIDAR models, the study quantified pillar width variations and conducted rock mass characterization using Rock Quality Designation (RQD), Rock Mass Rating (RMR), and the Geological Strength Index (GSI). A comparison between designed and actual pillar geometries revealed a 21.5% width reduction, which was incorporated into a revised LaModel simulation. The findings underscore the need to integrate empirical and numerical modeling approaches for a more comprehensive assessment of pillar stability.
By integrating empirical strength equations into numerical modeling software, this research aims to bridge that gap for underground stone mines, improving the reliability of pillar stability assessments. The enhanced stability mapping will offer a valuable resource for underground stone mine operators to identify potential hazard zones and mitigate the risks of catastrophic collapses
Machine Learning and UASs for Managing Autumn Olive (Elaeagnus umbellata) on Reclaimed Surface Mines
No full textThis research introduces an innovative approach for managing autumn olive (Elaeagnus umbellata) on reclaimed surface mines through the integration of machine learning algorithms and unmanned aerial systems. The proliferation of autumn olive presents significant ecological challenges on disturbed landscapes, necessitating more efficient detection and control methods. This study evaluated Random Forest classification and deep learning approaches using the U-Net architecture for identifying autumn olive across four phenological stages using high-resolution imagery. The RGB U-Net model achieved F1-scores of 0.927, 0.912, and 0.871 for autumn olive detection during peak, late, and senescence stages respectively, outperforming both multispectral and vegetation index composite models. Temporal analysis revealed optimal detection windows during peak and late growing seasons when autumn olive characteristics diverge the most from native vegetation. Feature importance analyses identified NIR and red-edge indices as valuable for early and peak detection, while visible-band and soil-adjusted indices became important during senescence. Unmanned aerial herbicide applications demonstrated effective control with minimal impact on surrounding vegetation and reduced labor requirements. This integrated technological approach represents a promising framework for invasive species management on reclaimed mine lands, offering enhanced accuracy, efficiency and cost-effectiveness compared to traditional management practices
Artificial Intelligence in Ethics and Society
Full text linkThis section explores the ethical dilemmas, social impacts, bias and fairness of AI use
Social Support and Negative Affective Outcomes Among Older Adults: Does Valuing Autonomy Matter?
Full text linkWhile not a normal part of aging, depression is a concerning psychiatric condition in late life. Depression is a significant predictor of suicide and the highest rates of suicide occur in middle aged and older adult men. One factor that may protect against depression and suicidal behavior among older adults is social support. Social support has been demonstrated as a significant factor in health and well-being. Perceived social support has consistently been linked to beneficial outcomes, however, received support has mixed results with some studies even finding received support to be harmful. For individuals who highly value autonomy, it may be more difficult to handle loss of ability through the aging process. Receiving help could lead to a sense of loss of control, and this could lead to adverse outcomes in people who highly value autonomy. The current study investigated how various types of social support relate to negative affective outcomes and the moderating effect of autonomy on the relationship between received support and negative affective outcomes. Data were collected online through CloudResearch and 647 older adults were recruited. Participants completed measures of functional impairment, social support (perceived, received, and network), depressive symptoms, suicidal behavior, and autonomy. Perceived and received support each significantly predicted depressive symptoms and suicidal behavior. Autonomy significantly moderated the relationships between perceived and received support and depressive symptoms
A Quality Improvement Initiative to Decrease Sugammadex Expenditures
Full text linkAbstract
A Quality Improvement Initiative to Decrease Sugammadex Expenditures
Jordan Gardo
Introduction/Background: The manufacturer’s suggestion in the dosing of the Sugammadex is
generally dosed at 2-4 mg/kg of total body weight (TBW) depending on the extent of
neuromuscular blockade. Evidence suggests that in the morbidly obese population, this
can lead to excessive dosing due to the drug\u27s hydrophilic properties, making it less cost-
effective. Dosing based on adjusted body weight (ABW) leads to dose reductions while
achieving full reversal of neuromuscular blockade as measured by quantitative train-of-
four monitoring, resulting in lower costs from decreased vial usage.
Purpose: The purpose of this project was to implement adjusted body weight dosing of
sugammadex to decrease the cost associated with the drug while maintaining patient
safety. The project utilized a combination of evidence-based education, intraoperative
decision support, and email feedback to promote ABW dosing while ensuring complete
neuromuscular blockade reversal occurred, as indicated by train-of-four monitoring.
Intervention: The Certified Registered Nurse Anesthesiology (CRNA) department at a
community hospital received education via PowerPoint presentation on the new dosing
method, the evidence supporting it, and how to determine the dose. To maintain
consistency, the department received cyclical, specific feedback and support throughout
the project.
Methods: This project employed the Institute for Healthcare Improvement (IHI) improvement
model as its framework. Within this model, the Plan-Do-Study-Act (PDSA) system
functioned as a cyclical process to guide the quality improvement initiative for
implementing adjusted body weight dosing for sugammadex in morbidly obese patients.
Results: Nineteen post-intervention and thirteen pre-intervention patients with BMI ≥ 40 were
included. ABW-based sugammadex dosing was utilized in 6 of 19 post-intervention cases
(31%). Compared to TBW dosing, ABW dosing reduced the average drug cost from
139.03. Total cost savings over three PDSA cycles equaled 5,164.03 at the observed adoption rate. A t-test comparing
post-intervention ABW vs. TBW costs yielded a statistically significant result (p =
0.004), supporting the intervention’s effectiveness in reducing expenditures without
compromising neuromuscular recovery. Neuromuscular blockade reversal was 100%
effective. However, provider adherence was lower than expected (31%), indicating a
need for improved engagement strategies. No adverse clinical outcomes were observed,
and the project showed strong potential for cost savings with further optimization.
Conclusions: ABW dosing for sugammadex offers a feasible and cost-effective alternative to
recommended TBW-based dosing in morbidly obese patients. With just a 50% adoption
rate, dosing based on ABW could save approximately $8,333.11 annually. This
highlights the financial benefits and suggests that higher adoption rates could lead to
even greater savings. Future efforts should focus on increasing provider engagement,
adding a permanent display of ABW in the electronic medical record, and expanding
implementation to enhance its impact. These findings support ABW dosing as a viable
strategy for reducing medication costs while maintaining clinical efficacy
Police Abuse in America and the Search for Remedy
Full text linkThe dissertation contends that, despite many diligent efforts—from mass protests to a presidential task force—America is not yet on path to remedying its outsized patterns of police abuse. The abuse problem is broadly characterized herein through a “triad” of over-enforcement, excessive force, and racial discrimination. The Washington Post’s “Fatal Force” database, covering the years 2015 through 2024, is offered as a bellwether of American progress in addressing its police abuse; and, it is observed, the nation’s yearly count of fatal police shootings of civilians has been increasing, rather than decreasing.
To help make sense of our lack of national progress, the frameworks that guide the extant remedial efforts are critically assessed. The four frameworks are police abolitionism, which regards the police as unreformable; and three others that are reform-based: evidence-based policing, democratic policing, and constitutional policing. The assessments are pursued through an adapted use of Thomas Kuhn’s Structure of Scientific Revolutions (1970), wherein each framework is regarded as a “scientific community.” For each framework, the study examines its “paradigms” (core beliefs) and “anomalies” (problems or unsolved puzzles), and asks whether the scientific community in question exhibits a capacity to grapple with and resolve anomalies—as reflected in the pertinent literature and in practice. One of these frameworks—constitutional policing—is partly assessed through a case study of the landmark stop-and-frisk federal lawsuit, Floyd v. City of New York (2013a) and its subsequent impact on police abuse in New York City.
The conclusion, though not advancing a new police abuse remedy as such, does imagine one potential new trajectory toward promoting progressive police reform nationally
Reuse of Calcium Carbonate (CaCo3) Recovered from Discarded Carpets as Filler in Fiber-Reinforced Polymer (FRP) Composites
Full text linkOver four billion pounds of carpet are discarded annually in the United States, making carpet waste a significant environmental concern. Calcium carbonate (CaCo₃) constitutes up to 45% of the mass of most synthetic carpets. Reusing this CaCo₃ as a filler in the rapidly growing fiber-reinforced polymer (FRP) industry, which is projected to reach USD 10.38 billion, presents a low-cost, practical approach to developing a market-based solution to post-consumer carpet waste.
This study investigates the reuse of CaCo₃ recovered from discarded carpet backing as a filler in FRP composites, focusing on its mechanical viability in comparison to virgin CaCo₃. The methodology involves a structured sieving process to isolate usable fractions, followed by resin mixing, viscosity measurement, and mechanical testing of both resin systems and glass fiber–reinforced polymer (GFRP) composites. Tension, compression, flexural, and short-beam shear tests were conducted on specimens fabricated via lab-scale hand lay-up and industrial pultrusion.
Three categories of GFRP coupons were prepared using virgin, #80-below, and #120-below CaCo₃ fillers, each tested with 20% and 30% filler content by total resin weight. The mechanical test results indicated that reused CaCo₃ can be used in GFRP fabrication, with less than a 30% reduction in tensile and flexural strength, and up to an 11% increase in stiffness compared to virgin-filled specimens.
To assess industrial applicability, the lab-scale process was replicated in collaboration with a major U.S. pultrusion manufacturer. Coupons extracted from these pultruded plates were tested and showed comparable mechanical behavior to virgin-filled composites.
Overall, the findings confirm that up to 20% by total matrix weight of sieved, recycled CaCo₃—particularly particles passing ASTM No. 80 sieve—can be effectively reused without significant compromise in structural performance. This research supports a scalable and sustainable open-loop recycling method for CaCo₃-rich carpet waste in FRP manufacturing, offering both environmental and economic benefits