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At least 1,081 records · Page 60

Caffeine enhances the anti-tumor effect of 5-fluorouracil via increasing the production of reactive oxygen species in hepatocellular carcinoma

The development of drug resistance affecting the prognosis of patients with hepatocellular carcinoma (HCC) leads to low survival rate of HCC patients. Caffeine is reported to have a function of protecting the liver and anti-tumor activity. Therefore, caffeine may be an ideal enhancer for HCC chemotherapy regimens. Our study showed that the combination of caffeine and 5-FU significantly inhibited the proliferation of HCC cells in vivo and in vitro comparing with caffeine or 5-FU monotherapy. The CI values of caffeine (0.5 mM) combined with 5-FU (25, 50 μM) were all less than 1, confirming that the utilization of drug combination has a synergistic inhibitory effect on the proliferation of HCC cells. Meanwhile, results of Western blot and TUNEL assays demonstrated that the apoptotic level of HCC cells in the combined group was significantly increased. The protein expression level of cleaved PARP was up-regulated, while the protein level of Bcl-2 and Bcl-xL was down-regulated. In addition, we found that ROS levels were increased in the 1 mM caffeine and 25 μM 5-FU combination group comparing with the control or single drug group. Taken together, this is the first study to demonstrate that the combination of caffeine and 5-FU inhibits HCC cells proliferation and promotes cellular apoptosis by regulating intracellular ROS production. The present data provides a basis for the application of caffeine combined with 5-FU as a novel chemotherapy regimen for HCC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Decentralized Voltage Control of Large-Scale Distribution System with PVs Based on MADRL

This paper proposes a model-free decentralized control framework for the voltage regulation of large-scale distribution systems through the coordinated control of PV inverters. This is achieved by developing a novel interaction mechanism between the surrogate model and the centralized training and decentralized execution multiagent deep reinforcement learning framework. Specifically, the sparse Gaussian processes regression method is first utilized to develop the surrogate model of the original distribution system for reward calculation during the training stage, where each agent represents a sub-region in the centralized fashion for coordination strategy learning. After that, the learned control rules are used to inform controllers within each sub-region for real-time decisions with only local measurements. Comparative tests among various methods on the EPRI Ckt5 test system demonstrate the effectiveness of the proposed method.

distribution system↗

A systems-level analysis of drought and density response in the model C4 grass Setaria viridis

The need for novel crops in an emerging bioenergy economy presents many challenges and opportunities for plant scientists. Plant breeding has been successful at transforming weedy species into some of the highest yielding crops on the planet. The plant domestication has led, in part, to an anticipated delivery of up to 1 billion dry tons of lignocellulosic feedstocks into the energy economy by 2030. However, The success of modern food crop breeding suggests that even greater advances can be made by developing the next generation of bioenergy feedstocks from C4 grass species that have been to date subjected to little or no breeding. The challenge we face is to exponentially accelerate the crop improvement process so that we can meet this level of bioenergy feedstock production. To achieve this unprecedented goal, it will be necessary to rapidly advance the process of plant breeding through large-scale biology, computational biology and systems approaches. Therefore, the goal of this proposal was to understand how productivity, drought tolerance and water use efficiency (WUE) are regulated at the genomic level in order to inform metabolic engineering and molecular-assisted breeding efforts.This necessitates the use of a model species that is closely related to less genetically tractable feedstock grasses such as Sorghum, switchgrass and Miscanthus. To achieve this we have significantly enhanced the utility of Setaria viridis as a model C4 species for system biology. This was achieved through field, greenhouse and laboratory experiments to survey a breadth of environments and explore the potential of gene networks to predict physiological responses across environments. We challenged plants under abiotic stresses to examine the plasticity of the network and identify targets for future manipulation. Finally, we have identified promising new gene engineering technologies to modify genetic networks in this model C4 species to understand and enhance abiotic stress tolerance. The outcomes of this project led to 1) identification of gene regulatory and metabolic networks important for adaptation to low water availability and high-density plantings, which lead to a greater understanding of the physiology underlying these adaptations and 2) we developed technologies to measure important water use efficiency traits and to precisely control gene insertion and replacements events for large scale engineering of pathways in model and target feedstocks.

59 BASIC BIOLOGICAL SCIENCES↗

Comparative Cost Analysis of Spent Nuclear Fuel Management Alternatives

This report presents a comparative analysis of spent nuclear fuel management options to support the U.S. Department of Energy (DOE). Specifically, a set of scenarios was constructed to represent a range of possible combinations of alternative spent fuel management approaches. Analyses were performed to provide simple and credible estimates of relative costs to the U.S. government and to the nuclear utilities for moving forward with each scenario. The analyses of alternatives and options related to spent nuclear fuel management presented in this report are based on technical and programmatic considerations and do not include an evaluation of relevant regulatory and legal considerations (e.g., needs for new or modified regulations or legislation). This report has been prepared for informational and comparison purposes only and should not be construed as a determination of the legal permissibility of specific alternatives and options. No inferences should be drawn from this report regarding future actions by DOE. To the extent this report conflicts with provisions of the Standard Contract, those provisions prevail.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Autonomous System Inference, Trojan, and Adversarial Reprogramming Attack and Defense (Final)

In the world of ever-advancing technology, Autonomous Systems (AS) find extensive application, bolstering functionalities of critical infrastructures such as nuclear power plants. These systems, however, are increasingly becoming a target for nefarious activities, namely through inference attacks, trojan attacks, and adversarial reprogramming. This paper delves into a comprehensive exploration of machine learning (ML)-driven autonomous control systems within advanced nuclear reactor designs, revealing the vulnerabilities and proposing strategies for defense against potential cyber-attacks. Advanced cyber-attacks against critical infrastructure and the energy sector are becoming more common. With the invention of autonomous control systems (ACS) within advanced nuclear reactor designs, system designers, reactor operators, and regulators must consider cybersecurity during the design and operational phases. This article provides a cyber threat assessment of machine learning (ML)- based digital twinning (DT) technologies in the context of advanced reactor ACS. A cyber-physical testbed was created to emulate nuclear reactor digital instrumentation and controls (I&C) and act as a basis for the ACS. The ACS was designed as two plant-level DTs predicting reactor malfunctions and determining control actions and two component-level DTs responsible for classifying component states and forecasting component inputs and outputs (I/O). Two duplicate ACS designs– one using a traditional ML framework and one using an automated ML (AutoML) framework– were created and tested against cyber-attacks on training data, real-time process data, and ML model architectures to determine their respective qualitative cyber-risk in terms of likelihood and impact. Both frameworks showed similar cyber-resilience against training, real-time, and ML architecture attacks, proving that neither is inherently more secure. Recommended safeguard and security measures are posed to system designers, reactor operators, and regulators to maintain the cybersecurity of ML-based DT technologies such as ACS, prompting a holistic view of shared responsibility for maintaining cyber-secure ML-based systems. As global reliance on generation III reactors begins to be critically assessed, the evolution towards advanced reactor systems utilizing digital instrumentation and controls (I&C) becomes not merely preferable, but essential. The integration of semi and fully autonomous control systems (ACS), powered by digital I&C and machine learning (ML)-based digital twinning (DT) technologies, emerges as a potent strategy to mitigate operations and maintenance costs, thereby enhancing the economic feasibility of novel reactor designs. However, with a staggering 500% and 380% increase in cyber-attacks reported against the energy sector by the United States Department of Energy (DoE) and the European Union respectively, a surge in cyber vulnerabilities specifically targeting the nuclear industry has been 2 markedly observed. Notable incidents, such as the W32.Ramnit spyware infiltration at the Gundremmingen nuclear power plant in Germany and the Dtrack spyware intrusion at the Kudankulam nuclear power plant in India, while not directly compromising core industrial control systems (ICS), underscore a compelling necessity to fortify cybersecurity protocols in safeguarding reactor systems against increasingly adept digital adversaries. In light of this, our investigation extends beyond conventional cybersecurity parameters, diving into the intricate web of potential vulnerabilities woven into ML-based DTs and ACS in advanced reactor systems. A crafted cyber-physical testbed and preliminary ACS were devised to act as a mirror, reflecting potential configurations of advanced reactor control designs. Moreover, this study is intertwined with a scrutinization of ML models, developed either through conventional, manually tuned methodologies or via automated means through AutoML, probing into their cyber-risk profiles within operational technology (OT) environments. Expanding on this, two distinct ACS blueprints were forged – one navigating through the corridors of traditional ML and the other traversing the path of AutoML – in an effort to holistically encapsulate the considerations pivotal to ML-based DT control system design. Employing the SANS Institute Industrial Control System (ICS) Kill Chain and the MITRE ATT&CK Tactics, Techniques, and Procedures (TTP) framework, a structured analysis was conducted, launching three targeted attacks against the training dataset, real-time dataset, and ML models, therein dissecting the potential cyber-attack implications against both ML frameworks within an ACS milieu. It is essential to note that three distinct categories of attacks were conducted against both ACS configurations, each encompassing three distinct ML-based DTs, cumulating in a total of 18 varied attacks. This exploration extends into the realms of Autonomous System Inference, Trojan, and Adversarial Reprogramming Attack and Defense, unraveling vulnerabilities, and opportunities for fortified defenses against such intrusions, particularly where ML-driven technologies, and by extension, ACS, are deployed. Final recommendations, articulated through a lens of security, safeguard, and implementation considerations, are presented for both traditional and AutoML models, anchoring upon the existing knowledge landscape and ML-based DT modeling for ACS, and are offered as a beacon to guide the nuclear industry through the intricate cybersecurity challenges that lie ahead.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Beneficial Use of Harvested Ponded Fly Ash and Landfilled FGD Materials for High-Volume Surface Mine Reclamation

The overall motivation of this project was to demonstrate at laboratory, bench-scale, and full-scale demonstration levels that (a) coal ash surface impoundments can go through closure by removal as per USEPA and state regulations so that the material can be used as is (other than draining free water using CCRs piles) in high-volume beneficial applications, (b) FGD material from closed out FGD facilities can be excavated and recompacted for coal mine reclamation, and (c) harvested CCRs can be beneficially utilized (providing a net environmental gain) in large-volumes for reclamation at abandoned coal mine sites across the US, especially in the Eastern and Midwest coal mining regions. The objectives of this project were to: 1) promote the safe and cost-effective closure by removal of coal ash impoundments, 2) harvest landfilled FGD, and 3) promote the high-volume beneficial use of these harvested CCRs in the reclamation of abandoned surface coal mine sites across the eastern and midwestern coal mining regions of the United States. The major tasks carried out for this project are summarized below: 1) Conesville Full-Scale Demonstration Project: About 2 million tons of harvested CCR materials from the closure by removal of an inactive fly ash pond and an adjacent old FGD landfill were used for the full-scale demonstration project to fully reclaim a nearby partially completed abandoned surface coal mine. Site monitoring for the project duration was carried out and results are discussed. 2) Laboratory Testing: Geotechnical and environmental testing of harvested ponded fly ash and landfilled FGD material at the former Conesville power plant were carried out. Completing the laboratory testing allowed for QA/QC for the full-scale site construction and informed the formulation of the risk analysis. 3) Risk Analysis: We developed a reliable computational model for fate and transport. We used these models and the rich set of monitored data for the Conesville site to analyze risks to human health and ecological risks associated with high-volume surface mine reclamation using harvested CCRs. 4) GIS Siting Study: A Geographic Information System (GIS) study was carried out for three states in the Eastern coal mining region and two states in the Midwest coal region. This effort provided site specific GIS information for five states and allowed us to establish protocols that other states can follow in implementing their own state specific GIS study.

01 COAL, LIGNITE, AND PEAT↗

Offset-Stoichiometric Reflowable Composite Bonding Method with Adhesive for Mitigating Strict Faying Surface Tolerances

Inherent susceptibility of adhesive bonds to miniscule quantities of contamination can cause undetectable weakened bonds. For this reason, the Federal Aviation Administration (FAA) places strict regulations on adhesively bonded joints in primary aircraft structures. To meet certification requirements aircraft manufactures resort to redundant load paths in the form of fasteners which inherently add weight to the structure and increase manufacturing time. In prior work, a secondary bonding technique called AERoBOND was developed, which utilized off-stoichiometric epoxymatrix resins to facilitate reflow and diffusion of the resin within the joint interface during a secondary bonding/cure process, thus achieving a bond similar to a co-cured joint. However, the AERoBOND process required tight spatial tolerances between the two parts being joined. This study examined the utilization of conventional adhesive with the AERoBOND method to act as a filler in the joint line, effectively reducing the need for tight tolerances on the joining parts and serving as a flexible alternative for existing manufacturing processes. Ultrasonic inspection, optical microscopy, and ASTM International standard tests were performed to analyze the joints for defects and to quantify the mode-I and mode-II interlaminar fracture toughness and short beam strength of the proposed methodology with varying manufacturing parameters. The comprehensive results indicate that the AERoBOND+ method with and without surface preparation performs comparably to co-cured and conventional, adhesively bonded joints when secondary cured in an autoclave with 791 kPa of pressure. As an example, the AERoBOND+ panel without surface preparation bonded with 791 kPa of pressure (referred to as AB+3 throughout paper) had a mode-I fracture toughness (G Ic ) of 0.643 kJ/m 2 and a mode-II fracture toughness (G IIc ) of 4.000 kJ/m 2 in the non-precracked condition and 4.218 kJ/m 2 in the precracked condition at the adhesive-to-prepreg interface. These results were 96%, 142%, and 217%, respectively, of a co-cured baseline panel (referred to as C1 throughout paper).

Composites↗

Development of a Technical Standard for Radiological Characterization of DAW - 19552

Since the Manhattan Project, the U.S. Department of Energy (DOE) and its predecessor agencies have performed a wide mission involving nuclear materials and weapons development, production, testing, and modernization. While the initial mission components relied heavily upon reactor physics and chemistry, the environmental programs have increasingly relied upon development of more accurate and effective measurement methodologies to determine the radiological and chemical properties of the unique waste streams that were generated during the weapons production and testing mission. During the ongoing site cleanup program, the DOE laboratories and former production sites have developed a wide range of site-specific processes and procedures for conducting radiological characterization of dry active waste (DAW) that is managed as low-level radioactive waste. This has resulted in a Complex-wide variability among sites with respect to the methodologies and instrumentation used to characterize individual waste streams. The DAW-type waste was selected for development of a characterization standard since it is a simple, voluminous, and repetitive waste stream with a substantial knowledge base, established experience history at multiple site locations, and the potential for realization of programmatic benefits though standardization. Implementation of a consistent, standardized approach to DAW characterization will take advantage of multiple applications for a technology that is both mature and stable. The DAW characterization process is repetitive and lends itself to implementation at a wide range of operating locations - resulting in economies of scale, compliance with regulatory requirements, and consistent implementation of procedures which support design, operations, maintenance, and management of facilities, activities and environmental restoration programs. In response to a request from DOE, the Energy Facility Contractors Group (EFCOG) Waste Management Working Group (WMWG) is supporting the development of a new DOE Technical Standard for Radiological Characterization of DAW. The purpose of the proposed new standard is to provide a technical resource that integrates and enhances the utilization of current site-specific methodologies and processes. An EFCOG/WMWG technical team has prepared a Technical Basis Document (TBD) to support the development and utilization of the new standard. The TBD provides detailed reference information for use by site personnel when implementing the guidance to be provided in the standard. It also provides the rationale for and details concerning the recommended technical approaches for radiological characterization of representative DAW-type waste streams. The TBD is an essential resource and will be included as an appendix to the proposed standard. Formulation of the new standard will draw upon the information contained in the TBD in order to integrate and improve the utilization of current site-specific methodologies and processes. It will also include a comparison of current radiological characterization methodologies to determine which ones are most reliable and effective in producing relevant and valid data. In view of the long history and participation by several agencies in the regulation of nuclear programs, existing Voluntary Consensus Standards have also been identified in the TBD and will be referenced for relevancy and applicability to the new proposed standard. A Project Justification Statement (PJS) was also developed by the EFCOG/WMWG Team. Following internal Team review and approval by EFCOG, the draft PJS was submitted through Argonne National Laboratory (ANL) and the DOE Argonne Site Office Technical Standards Managers for review and approval by the DOE Argonne Site Office Manager. After resolution of comments and approval by the Manager, the PJS will be submitted to the DOE/HQ Technical Standards Program Manager (TSPM) for formal coordination. Following resolution of technical comments received during the PJS coordination process and receipt of a technical standards project number assigned by the TSPM, the Team will confirm the overall preparation schedule and develop an Internal Draft Technical Standard for coordination with the DOE Argonne Site Office. Following comment resolution, the Team will then prepare a Coordination Draft for submittal to the DOE Technical Standards RevCom review process and will respond to comments generated during this Complex-wide review. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

In vivo maternal and in vitro BPA exposure effects on hypothalamic neurogenesis and appetite regulators

Highlights: • BPA exposure during fetal period and in vitro BPA treatment alters neurogenesis. • BPA increases hypothalamic neuroprogenitor cell proliferation and differentiation. • BPA increases protein expression of hypothalamic neurogenic bHLH factors. • BPA promotes protein expression of hypothalamic appetite versus satiety neuropeptide. • BPA promotes neuronal versus astroglial lineage. In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured. For in vitro BPA exposure, primary hypothalamic NPCs from healthy newborns were utilized. In both cases, we studied the effects of BPA on NPC proliferation and differentiation, including putative signal and appetite factors. Maternal BPA increased hypothalamic NPC proliferation and differentiation in newborns, in conjunction with increased neuroproliferative (Hes1) and proneurogenic (Ngn3) protein expression. With NPC differentiation, BPA exposure increased appetite peptide and reduced satiety peptide expression. In vitro BPA-treated control NPCs showed results that were consistent with in vivo data (increase appetite vs satiety peptide expression) and further showed a shift towards neuronal versus glial fate as well as an increase in the epigenetic regulator lysine-specific histone demethylase1 (LSD1). These findings emphasize the vulnerability of stem-cell populations that are involved in life-long regulation of metabolic homeostasis to epigenetically-mediated endocrine disruption by BPA during early life.

54 ENVIRONMENTAL SCIENCES↗

Damaged Fuel in the United States - 20325

Throughout the history of commercial nuclear power plant operations in the U.S., many fuel assemblies have lost the capability to perform all of their desired functions. Since they can no longer be handled, stored, or transported in accordance with established regulations, they are classified as damaged fuel. The causes of these failed assemblies are diverse and plant-specific. The majority of these failed assemblies are contained in damaged fuel cans to be used in conjunction with storage and/or transportation systems. These systems have a limited number of slots that can be filled with damaged fuel cans. A damaged fuel can is generally a stainless-steel container that confines damaged spent nuclear fuel (SNF) and is closed at one end by mesh endpoints that allow gaseous and liquid media to escape but minimize the dispersal of gross particulate material. Out of extreme caution, a few reactors have loaded high burnup fuel into damaged fuel cans. Damaged fuel is not licensed for storage or transport in the U.S. because relevant regulations do not specify exactly how to classify damaged fuel. Instead, these regulations license/certify packages that specify approved contents. Damaged fuel must be included among the approved contents to be considered acceptable. In many cases, damaged SNF is encapsulated in damaged fuel cans to ensure it can confine gross fuel particles, debris, and/or damaged assemblies to known volumes within loaded casks. A damaged fuel can may then be utilized in the same way as an assembly in a storage and transportation system. Some storage cask systems utilize top and bottom plugs to confine debris in damaged fuel. The most recent domestic documentation on damaged SNF was published by the U.S. Energy Information Administration (EIA), which used data from U.S. reactors compiled from 1968 to June 30, 2013, to produce Form GC-859, 'Nuclear Fuel Data Survey.' According to this form, there were 136,821 boiling water reactor (BWR) SNF assemblies and 104,647 pressurized water reactor (PWR) SNF assemblies, for a combined total of 241,468. Of these, 4,521 were classified as failed. Some were also disassembled and the fuel rods or pieces of fuel rods combined to make consolidated assemblies. These consolidated assemblies may include damaged fuel or were perhaps consolidated as part of a demonstration project. The GC-859 data includes 2,550 consolidated assemblies containing 0 - 264 entire fuel rods. These consolidated assemblies could be placed in single assembly canisters and stored in the spent fuel pool. For dry storage and transportation, a single assembly canister is generally placed in each damaged fuel can. In addition to the consolidated assemblies, 2,391 un-canistered fuel rod pieces exist, which were removed from 494 assemblies. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

The Radiation Oncology Job Market: The Economics and Policy of Workforce Regulation

Examinations of the US radiation oncology workforce offer inconsistent conclusions, but recent data raise significant concerns about an oversupply of physicians. Despite these concerns, residency slots continue to expand at an unprecedented pace. Employed radiation oncologists and professional corporations with weak contracts or loose ties to hospital administrators would be expected to suffer the greatest harm from an oversupply. The reduced cost of labor, however, would be expected to increase profitability for equipment owners, technology vendors, and entrenched professional groups. Policymakers must recognize that the number of practicing radiation oncologists is a poor surrogate for clinical capacity. There is likely to be significant opportunity to augment capacity without increasing the number of radiation oncologists by improving clinic efficiency and offering targeted incentives for geographic redistribution. Payment policy changes significantly threaten radiation oncologists' income, which may encourage physicians to care for greater patient loads, thereby obviating more personnel. Furthermore, the implementation of alternative payment models such as Medicare's Oncology Care Model threatens to decrease both the utilization and price of radiation therapy by turning referring providers into cost-conscious consumers. Medicare funds the vast majority of graduate medical education, but the extent to which the expansion in radiation oncology residency slots has been externally funded is unclear. Excess physician capacity carries a significant risk of harm to society by suboptimally allocating intellectual resources and creating comparative shortages in other, more needed disciplines. There are practical concerns associated with a market-based solution in which medical students self-regulate according to job availability, but antitrust law would likely forbid collaborative self-regulation that purports to restrict supply. Because Congress is unlikely to create one central body to govern residency controls for all specialties, we recommend better reporting of program-specific employment metrics and careful, intellectually honest re-evaluation of existing Accreditation Council for Graduate Medical Education accreditation standards.

61 RADIATION PROTECTION AND DOSIMETRY↗

Systemic Microgravity Response: Utilizing GeneLab to Develop Hypotheses for Spaceflight Risks

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗

Metabololipidomic profiling of functional immunoresolvent clusters and eicosanoids in mammalian tissues

Highlights: • New methods for metabololipidomics of specialized proresolving mediators (SPM) and classic eicosanoids. • Illustration from human blood coagulation. • Illustration from solid tumor. • Regulation of SPM biosynthesis by adenosine and adenosine deaminase. Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels. Here, we review novel approaches to understand the relationship(s) between coagulation and resolution of inflammation and infection. To determine whether coagulation is involved in host-protective actions by lipid mediators, we used a metabololipidomic-based profiling approach with human whole blood (WB) during coagulation. We identified recently temporal clusters of endogenously produced pro-thrombotic and proinflammatory lipid mediators (eicosanoids), as well as specialized proresolving mediators (SPMs) in this vital process. In addition to the classic eicosanoids (prostaglandins, thromboxanes and leukotrienes), a specific SPM cluster was identified that consists of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B{sub 4}, and maresin 1, each of which present at bioactive concentrations (0.1–1 nM). The removal of adenosine from coagulating blood samples significantly enhances SPM amounts and unleashes the biosynthesis of RvD3, RvD4, and RvD6 evident following rapid snap freezing with centrifugation before extraction and LC-MS-MS. The classic cyclooxygenase inhibitors, celecoxib and indomethacin, that block thromboxanes and prostanoids do not block production of the clot-driven SPM cluster. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targets leukocytes at the single-cell level, directly activating extracellular signaling in human neutrophils and monocytes. Human whole blood treated with the components of this SPM cluster enhanced both phagocytosis and killing of Escherichia coli by leukocytes. Thus, we identified a pro-resolving lipid mediator circuit and specific SPM cluster that promotes host defense. This new lipid mediator (LM)-SPM metabololipidomic approach now provides accessible metabolomic profiles in healthy and diseased human tissues, including cancer, for precision and personalized medicine.

60 APPLIED LIFE SCIENCES↗

Common Column Identification for Table Similarity Detection in Electrified Transportation Data Lakes

Electrified transportation often requires researchers and operators to interact with datasets from a wide range of sources and disciplines, such as transportation, power systems, public health, policies, and regulations. These datasets vary in quality and format, making it difficult to understand, preprocess, and identify key columns representing real-world entities or values for indexing and joining, which can negatively impact downstream analysis and operation. Existing solutions are limited, requiring extensive manual customization or data expertise to utilize. In this article, we propose a multi-layered approach to automatically identify key columns to expedite preprocessing and aid in analysis of electrified transportation data. Our method leverages a dynamic ontology to identify common fields and an information theory-based strategy for edge cases that are difficult to generalize. Evaluations on a number of datasets from data.gov and kaggle.com show improved performance of our methods over several baseline techniques, and our ablation analyses illustrate the efficacy of individual components of our method. Our case studies also demonstrate that our methods have the potential to improve analysis of electrified transportation data and aid in automatic integration of such datasets.

33 ADVANCED PROPULSION SYSTEMS↗

Evaluation of performance indicators applied to a material recovery facility fed by mixed packaging waste

Highlights: • Material Flows assessment of a Material Recovery Facility has been realized. • Performance Indicators for a generic MRF have been proposed. • A Dashboard has been utilized to measure the facility performance. • Experimental values of incoming waste and output products composition are reported. - Abstract: Most of the integrated systems for municipal solid waste management aim to increase the recycling of secondary materials by means of physical processes including sorting, shredding and reprocessing. Several restrictions prevent from reaching a very high material recycling efficiency: the variability of the composition of new-marketed materials used for packaging production and its shape and complexity are critical issues. The packaging goods are in fact made of different materials (aluminium, polymers, paper, etc.), possibly assembled, having different shape (flat, cylindrical, one-dimensional, etc.), density, colours, optical properties and so on. These aspects limit the effectiveness and efficiency of the sorting and reprocessing plants. The scope of this study was to evaluate the performance of a large scale Material Recovery Facility (MRF) by utilizing data collected during a long period of monitoring. The database resulted from the measured data has been organized in four sections: (1) data related to the amount and type of inlet waste; (2) amount and composition of output products and waste; (3) operating data (such as worked hours for shift, planned and unscheduled maintenance time, setting parameters of the equipment, and energy consumption for shift); (4) economic data (value of each product, disposal price for the produced waste, penalty for non-compliance of products and waste, etc.). A part of this database has been utilized to build an executive dashboard composed by a set of performance indicators suitable to measure the effectiveness and the efficiency of the MRF operations. The dashboard revealed itself as a powerful tool to support managers and engineers in their decisions in respect to the market demand or compliance regulation variation as well as in the designing of the lay-out improvements. The results indicated that the 40% of the input waste was recovered as valuable products and that a large part of these (88%) complied with the standards of the recycling companies. The evaluation of the indicators led to the decision to modify the layout to improve the interception of some polymers for which the performance indicators were poor. In particular, two additional optical sorters have to be inserted to increase the yield indicator and to the overall performance of the facility. Definitely, the results of the work allowed to: increase the yield and purity of products’ flows; ensure the compliance of waste flows; increase the workability.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Coarse-Grained Modeling Elucidates Differential Metabolism of Saccharomyces cerevisiae under Varied Nutrient Limitations

Microorganisms such as Saccharomyces cerevisiae have a native ability to adapt their metabolism to varying nutrient conditions. Understanding their responses to nutrient limitations is critical for decoding cellular physiology and designing strategies for metabolic engineering. While the influence of carbon availability on yeast metabolism has been extensively studied, the role of nitrogen availability remains relatively underexplored. In this study, we utilized a coarse-grained kinetic model to systematically analyze and compare the effects of carbon and nitrogen limitations on yeast metabolism. Our model successfully revealed the differential metabolic characteristics of S. cerevisiae under carbon- and nitrogen-limited chemostat conditions. It also highlighted the significance of protein activity regulation at varying carbon-to-nitrogen ratios, and elucidated distinct strategies employed to maintain ATP homeostasis. Furthermore, this study provides a computational tool for investigating yeast physiology under nutrient limitations and offers quantitative and mechanistic insights into yeast metabolism.

59 BASIC BIOLOGICAL SCIENCES↗

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.

59 BASIC BIOLOGICAL SCIENCES↗

Data for "Implications of Zoning Ordinances for Rural Utility-Scale Solar Deployment and Power System Decarbonization in the Great Lakes Region".

This dataset includes the Energy Zoning Database and geographic shapefiles used to identify suitable rural areas for utility-scale solar development. Additionally, it contains the input data required for the capacity expansion model, including information on existing electric generators and their associated costs, solar resource potential, and transmission infrastructure data. These datasets collectively support the analysis presented in the paper, ensuring a comprehensive assessment of zoning regulations, land suitability, and the economic and technical feasibility of solar deployment in rural areas.

Owusu-Obeng, Papa Yaw (ORCID:0000000334385183)↗