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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
NASA NTRS2014

Persistent Expression Changes of Fibrosis Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.

Zhang, Ye↗
NASA NTRS2014

Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust‐induced changes of the expression of fibrosis‐related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate‐buffered saline (PBS). A zymosan‐induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real‐time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose‐ and time‐dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust‐induced toxicity in humans on earth.

Zhang, Ye↗
NASA NTRS1990

Effect of ammonium sulfate, ammonium chloride and root-zone acidity on inorganic ion content of tobacco

Tobacco plants (Nicotiana tabacum L. cv NC82) were supplied with (NH4)2SO4 or NH4Cl at root-zone pH of 6.0 and 4.5 in hydroponic culture for 28 days. Dry matter accumulation, total N and C content, and leaf area and number were not affected by the NH4+ source or root-zone pH. Plants supplied with NH4Cl accumulated up to 1.2 mM Cl g DW-1, but accumulated 37% less inorganic H2PO4- and 47% less SO4(2-) than plants supplied with (NH4)2SO4. The large Cl- accumulation resulted in NH4Cl- supplied plants having a 31% higher inorganic anion (NO3-, H2, PO4-, SO4(2-), and Cl-) charge. This higher inorganic anion charge in the NH4Cl-supplied plants was balanced by a similar increase in K+ charge. Plants supplied with NH4Cl accumulated greater concentrations of Cl- in leaves (up to 5.1% of DW) than plants supplied with (NH4)2SO4 (less than -% DW). Despite the high Cl- concentration of leaves in NH4Cl supplied plants, these plants showed no symptoms of Cl- toxicity. This demonstrates that toxicity symptoms are not due solely to an interaction between high Cl- concentration in tissue and NH4+ nutrition. The increase in root-zone acidity to pH 4.5 from 6.0 did not induce toxicity symptoms.

NASA Program CELSS↗
DOE OSTI2024

Transcriptomics-Based Points of Departure for Daphnia magna Exposed to 18 Per- and Polyfluoroalkyl Substances

Here, per- and polyfluoroalkyl substances (PFAS) represent a large group of contaminants of concern based on their widespread use, environmental persistence, and potential toxicity. Many traditional models for estimating toxicity, bioaccumulation, and other toxicological properties are not well suited for PFAS. Consequently, there is a need to generate hazard information for PFAS in an efficient and cost-effective manner. In the present study, Daphnia magna were exposed to multiple concentrations of 22 different PFAS for 24 h, in 96-well plate format. Following exposure, whole body RNA was extracted and extracts, each representing five exposed individuals, were subjected to RNA sequencing. Following analytical measurements to verify PFAS exposure concentrations, and quality control on processed cDNA libraries for sequencing, concentration-response modeling was applied to the data sets for 18 of the tested compounds, and the concentration at which a concerted molecular response occurred (transcriptomic point of departure; tPOD) was calculated. The tPODs, based on measured concentrations of PFAS, generally ranged from 0.03-0.58 µM (9.9-350 µg/L; interquartile range). In most cases, these concentrations were two orders of magnitude lower than similarly calculated tPODs for human cell lines exposed to PFAS. They were also lower than apical effect concentrations reported for seven PFAS for which some crustacean or invertebrate toxicity data were available, although there were a few exceptions. Despite being lower than most other available hazard benchmarks, Daphnia magna tPODs were, on average, four orders of magnitude greater than the maximum aqueous concentrations of PFAS measured in Great Lakes tributaries. Overall, this high throughput transcriptomics assay with Daphnia magna holds promise as a component of a tiered hazard evaluation strategy employing new approach methodologies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Green solvent-processable poly(3-hexylthiophene) derivative maintains high hole mobility in diodes

The development of environmentally sustainable fabrication methods for organic solar cells (OSCs) is critical to enable their large-scale adoption. Conventional solution-processed OSCs often rely on halogenated, toxic solvents that pose health and environmental risks, limiting their scalability. This is because π-conjugated polymers tend to have a low solubility in non-halogenated solvents. A common strategy to enhance solubility in alternative solvents is through the incorporation of polar solubilizing groups, often on every repeat unit of at least one monomer. However, too many polar side chains tend to disrupt favorable morphology and decrease charge transport properties. In this study, we demonstrate that a minimal degree of side chain functionalization can improve green solvent processability while preserving electrical performance. We tested this hypothesis using our previously reported random copolymer derivative of poly(3-hexylthiophene) (P3HT) where ∼10 mol% of the side chains are 6-pentanoatehexyl side chains. We find that this low-level functionalization significantly broadens the solvents that can be used to process P3HT to less toxic solvents such as o-xylene and anisole. Furthermore, the copolymer processed from greener solvents showed high hole mobilities (∼10⁻ 3 cm 2 /Vs by the Space-Charge Limiting Current method in diodes), comparable to P3HT films cast from toxic chloroform. These findings suggest that minimal side-chain modification is a viable strategy for expanding green solvent compatibility while preserving electrical performance, paving the way toward more sustainable organic semiconductor designs.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model

Although implicated as deleterious in many organisms, aneuploidy can underlie rapid phenotypic evolution. However, aneuploidy will be maintained only if the benefit outweighs the cost, which remains incompletely understood. To quantify this cost and the molecular determinants behind it, we generated a panel of chromosome duplications in Saccharomyces cerevisiae and applied comparative modeling and molecular validation to understand aneuploidy toxicity. We show that 74%–94% of the variance in aneuploid strains’ growth rates is explained by the cumulative cost of genes on each chromosome, measured for single-gene duplications using a genomic library, along with the deleterious contribution of small nucleolar RNAs (snoRNAs) and beneficial effects of tRNAs. Machine learning to identify properties of detrimental gene duplicates provided no support for the balance hypothesis of aneuploidy toxicity and instead identified gene length as the best predictor of toxicity. Our results present a generalized framework for the cost of aneuploidy with implications for disease biology and evolution.

genic load↗
DOE OSTI2024

Bioactivity Profiling of Chemical Mixtures for Hazard Characterization

Abstract The assessment and regulation of chemical toxicity to protect human health and the environment are done one chemical at a time and seldom at environmentally relevant concentrations. However, chemicals are found in the environment as mixtures, and their toxicity is largely unknown. Understanding the hazard posed by chemicals within the mixture is critical to enforce protective measures. Here, we demonstrate the application of bioactivity profiling of environmental water samples using the sentinel and ecotoxicology model species Daphnia to reveal the biomolecular response induced by exposure to real-world mixtures. We exposed a Daphnia strain to 30 sampled waters of the Chaobai River and measured the gene expression response profiles. Using a multiblock correlation analysis, we establish correlations between chemical mixtures identified in 30 water samples with gene expression patterns induced by these chemical mixtures. We identified 80 metabolic pathways putatively activated by mixtures of inorganic ions, heavy metals, polycyclic aromatic hydrocarbons, industrial chemicals, and a set of biocides, pesticides, and pharmacologically active substances. Our data-driven approach discovered both known bioactivity signatures with previously described modes of action and new pathways linked to undiscovered potential hazards. This study demonstrates the feasibility of reducing the complexity of real-world mixture toxicity to characterize the biomolecular effects of a defined number of chemical components based on gene expression monitoring of the sentinel species Daphnia.

Engineering↗
DOE OSTI2025

Exceptional NH 3 Detection by Cu(cyhdc) MOF Sensor Due to H 2 O Coadsorption

Metal–organic framework (MOF)-based electrical impedance sensors are a growing class of sensors that show utility in the detection of environmentally toxic gases. Detection of trace NH 3 has been particularly difficult to design due to the low electrical response of NH 3 . However, this has been circumvented by judiciously selecting a MOF that has enhanced electrical response to NH 3 due to coadsorption with predominant atmospheric gases such as water. Herein, an MOF Cu(cyhdc) based sensor has been successfully demonstrated for the enhanced detection of environmentally toxic NH 3 gas. The sensor shows a change in impedance when it is exposed to 5 ppm of NH 3 . At 20 °C, >30% relative humidity (RH) is necessary to elicit a change, with the response increasing with RH and reaching 3170× at 92% RH, producing the largest published response to NH 3 for a MOF direct electrical sensor. In the absence of water, no change is observed toward 5 ppm of NH 3 over 20–50 °C. Here, this electrical response is largely driven by huge decreases in the imaginary component of the impedance, attributed to increased capacitance at the surface of the MOF crystallites upon NH 3 and H 2 O coadsorption. Complementary structural and microstructural characterization proves that the Cu(cyhdc) crystalline structure and morphology remain intact under trace NH 3 and/or H 2 O adsorption. Despite extremely low NH 3 , loadings seen in TGA, XPS, and FT-IR confirm NH 3 and H 2 O adsorption, and changes to the metal-carboxylate IR peak positions are observed upon NH 3 adsorption. Concentrated primarily at the outer surfaces of the MOF crystallites, this NH 3 and H 2 O coadsorption effectively increases the surface capacitance across the Cu(cyhdc) powder and enables direct electrical detection of trace NH 3 . Together, these results demonstrate how coadsorption of specific molecules (H 2 O) can be used to enable the electrical detection of trace toxic gases that would otherwise not have produced a MOF sensor response.

ammonia↗
DOE OSTI2026

Rheinheimera sp . T2C2 Bacterial Biofilm for Bioremediation of Cobalt(II)

Toxic metals, including cobalt, are often the cause of the contamination of rivers and lakes in mining regions. Heavy metal water pollution has been linked to numerous human health problems, prompting the need for environmental remediation. Existing techniques for removing heavy metals from water, such as chemical precipitation and filtration, produce toxic waste, are costly, or require high power consumption for pumping. Biosorption is a potential alternative strategy that is cost-effective and uses readily available and naturally produced biomass and living material to absorb pollutants. Engineering living materials, such as biofilms, which consist of living cells and a secreted polymer matrix, offer the potential to integrate toxin sensing, sequestration, and metabolism capabilities of cells to improve pollution remediation strategies. Alternative biofilm producing candidates need to be explored to implement these material capabilities. Previous biosorption studies have primarily used bacterial biofilms from known pathogens and/or generated toxic waste in the form of the absorbent material combined with the heavy metal. Here, we describe a recently isolated bacterium called Rheinheimera sp. T2C2 that forms biofilms with promising biosorption characteristics. T2C2 is an aquatic bacterium with low nutrient requirements and high biofilm production that is not known to be pathogenic. We demonstrate (1) the efficacy of Rheinheimera sp. T2C2 as a biosorbent for cobalt bioremediation; (2) how biosorption is altered by water conditions to establish the efficacy of this strategy in different environments; and (3) how the metal can be released from the biofilm for metal recycling. Our findings will provide a living materials strategy that overcomes the existing barriers for bioremediation and improves the health of ecosystems and humans through heavy metal removal and recycling.

Rheinheimera↗
DOE OSTI2025

Dry electrodes with a printed cellulose–graphene ink for low-profile strain sensors in electromyography

Dihydrolevoglucosenone, commonly known as Cyrene, is a renewable and fully biodegradable cellulose-waste derived, environmentally friendly solvent, presenting a non-toxic alternative to N-methyl-2-pyrrolidone (NMP). Currently, solution-based processing of graphene and other similar van der Waals solids favor toxic solvents such as NMP, limiting their use for biosensing. However, with the use of Cyrene, bio-compatible printable devices are possible, and studies have already demonstrated its use in temperature and other biosensing methods through screen-printing. Screen-printing unfortunately often requires masks that constrain the minimum acquirable feature size to be above hundreds of centimeters and wastes material, adding to process complexity and cost. Conversely, inkjet-printing is an attractive alternative for the maskless patterning of hierarchically assembled structures, with micron length scales attainable. Graphene's high conductivity positions it ideally for long-wear sensors such as dry electrodes or respiration monitors. Here, we demonstrate the potential of Cyrene-based graphene inks through few-layer inkjet printing on flexible substrates for the first time, to produce non-toxic conductors toward a strain-mediated mechanism for biosensing, used to detect bodily motion for wearable electronics. The challenges overcome in this study include engineering ink chemistry and printing parameters such that Cyrene's relatively high viscosity compared to typical inkjet solvents, still allows for droplet ejection in a conventional material printer, yielding well-resolved clean line-edges in contrast to other solvents that exhibit diffuse line-edges possibly from stray droplets and ink-splashing. Temperature-dependent transport measurements on the inkjet-printed Cyrene-based graphene films showed the conductivity to be largely temperature-invariant but at lower temperatures below 100 K, conductivity decreased, likely as a result of increased inter-membrane separation arising from thermal contraction. Additionally, temperature-dependent Raman spectroscopy showed the red-shift in the G-band, 2D-band and D-band peaks, as temperature increased. As a result, by validating flexion motion detection of the proximal interphalangeal joint demonstrated in this study, our work is the first of its kind to successfully additively manufacture inkjet-printed Cyrene-based graphene strain sensors on flexible substrates for bio-sensing and wearables.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy

T-cell engaging (TCE) bispecific antibodies are potent drugs that trigger the immune system to eliminate cancer cells, but administration can be accompanied by toxic side effects that limit dosing. TCEs function by binding to cell surface receptors on T cells, frequently CD3, with one arm of the bispecific antibody while the other arm binds to cell surface antigens on cancer cells. On-target, off-tumor toxicity can arise when the target antigen is also present on healthy cells. The toxicity of TCEs may be ameliorated through the use of pro-drug forms of the TCE, which are not fully functional until recruited to the tumor microenvironment. This can be accomplished by masking the anti-CD3 arm of the TCE with an autoinhibitory motif that is released by tumor-enriched proteases. Here, we solve the crystal structure of the antigen-binding fragment of a novel anti-CD3 antibody, E10, in complex with its epitope from CD3 and use this information to engineer a masked form of the antibody that can activate by the tumor-enriched protease matrix metalloproteinase 2 (MMP-2). We demonstrate with binding experiments and in vitro T-cell activation and killing assays that our designed prodrug TCE is capable of tumor-selective T-cell activity that is dependent upon MMP-2. Furthermore, we demonstrate that a similar masking strategy can be used to create a pro-drug form of the frequently used anti-CD3 antibody SP34. This study showcases an approach to developing immune-modulating therapeutics that prioritizes safety and has the potential to advance cancer immunotherapy treatment strategies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Adaptive responses of Trichlorobacter lovleyi to nitrite detoxification reveal overlooked contributions of Geobacterales to nitrate ammonification

Abstract Poorly understood microorganisms “short-circuit” the nitrogen cycle via the dissimilatory nitrate reduction to ammonium to retain the element in agricultural lands and stimulate crop productivity. The prevalence of Geobacterales closely related to Trichlorobacter lovleyi in nitrate ammonification hotspots motivated us to investigate adaptive responses contributing to ammonification rates in the laboratory type strain T. lovleyi SZ. Here, we describe the identification of tightly regulated pathways for efficient nitrate foraging and respiration with acetate, an important intermediate of organic matter degradation that Geobacterales efficiently assimilate and oxidize. Challenging the established dogma that high carbon/nitrate ratios stimulate the reduction of nitrate to ammonium, T. lovleyi doubled rapidly across a wide range of ratios provided nitrate concentrations were low enough to prevent the accumulation of the toxic nitrite intermediate. Yet, excess electrons during hydrogenotrophic growth alleviated nitrite toxicity and stimulated the reduction of nitrate to ammonium even under conditions of severe acetate limitation. These findings underscore the importance of nitrite toxicity in the ammonification of nitrate by Geobacterales and provide much needed mechanistic understanding of microbial adaptations contributing to soil nitrogen conservation. This information is critical to enhance the predictive value of genomic-based traits in environmental surveys and to guide strategies for sustainable management of nitrogen fertilization as well as mitigation of green-house emissions and agrochemical leaching from agricultural lands.

Environmental Sciences & Ecology↗
DOE OSTI2024

Utilization of formic acid by extremely thermoacidophilic archaea species

The exploration of novel hosts with the ability to assimilate formic acid, a C1 substrate that can be produced from renewable electrons and CO 2 , is of great relevance for developing novel and sustainable biomanufacturing platforms. Formatotrophs can use formic acid or formate as a carbon and/or reducing power source. Formatotrophy has typically been studied in neutrophilic microorganisms because formic acid toxicity increases in acidic environments below the pKa of 3.75 (25°C). Because of this toxicity challenge, utilization of formic acid as either a carbon or energy source has been largely unexplored in thermoacidophiles, species that possess the ability to produce a variety of metabolites and enzymes of high biotechnological relevance. Here we investigate the capacity of several thermoacidophilic archaea species from the Sulfolobales order to tolerate and metabolize formic acid. Metallosphaera prunae, Sulfolobus metallicus and Sulfolobus acidocaldarium were found to metabolize and grow with 1–2 mM of formic acid in batch cultivations. Formic acid was co-utilized by this species alongside physiological electron donors, including ferrous iron. To enhance formic acid utilization while maintaining aqueous concentrations below the toxicity threshold, we developed a bioreactor culturing method based on a sequential formic acid feeding strategy. By dosing small amounts of formic acid sequentially and feeding H 2 as co-substrate, M. prunae could utilize a total of 16.3 mM of formic acid and grow to higher cell densities than when H 2 was supplied as a sole electron donor. These results demonstrate the viability of culturing thermoacidophilic species with formic acid as an auxiliary substrate in bioreactors to obtain higher cell densities than those yielded by conventional autotrophic conditions. Our work underscores the significance of formic acid metabolism in extreme habitats and holds promise for biotechnological applications in the realm of sustainable energy production and environmental remediation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Engineered Methylobacterium extorquens grows well on methoxylated aromatics due to its formaldehyde metabolism and stress response

ABSTRACT Lignin is a vast yet underutilized source of renewable energy. The microbial valorization of lignin is challenging due to the toxicity of its degradation intermediates, particularly formaldehyde. In this study, we engineeredMethylobacterium extorquensPA1 to metabolize lignin-derived methoxylated aromatics, vanillate (VA) and protocatechuate (PCA), by introducing thevanandpcagene clusters. Compared toPseudomonas putida,M. extorquensPA1 exhibited better formaldehyde detoxification, enabling robust growth on VA without accumulation of formaldehyde. Genetic analyses confirmed that formaldehyde oxidation and stress response systems, rather than C 1 assimilation, were important for VA metabolism. Additionally, VA and PCA were found to disrupt membrane potential, contributing to their inherent toxicity. Our findings establishM. extorquensPA1 as a promising chassis for lignin valorization and provide a framework for engineering formaldehyde-resistant microbial platforms. IMPORTANCE In developing biotechnological solutions for a circular economy, it is critical to valorize all parts of renewable resources, such as lignocellulose from vegetative components of agricultural crops and from bioenergy feedstocks. After chemical breakdown, the aromatics arising from lignin present significant challenges for use due to their toxicity. Here, we address one component of this challenge—the methoxy groups that get released as formaldehyde—and show that existing biotechnological platform organisms with strong formaldehyde metabolism, such asMethylobacterium extorquens, can be transformed into highly capable utilizers of methoxylated aromatics.

Microbiology↗
DOE OSTI2025

Development of the Table of Initial Isolation and Protective Action Distances for the 2024 Emergency Response Guidebook

The transportation of hazardous materials creates numerous opportunities for the release of toxic substances into the environment, whether caused by traffic accidents, train derailments, equipment failures, or human error. Such releases can pose acute hazards to the general public and to emergency response personnel who are the first to arrive at the scene. To help first responders determine whether a shipment is potentially hazardous and decide what actions should be taken if a toxic spill does occur, the Emergency Response Guidebook (ERG) is published by the U.S. Department of Transportation (DOT), Transport Canada, and the Secretariat of Transport and Communications of Mexico; with contributions from Centro de Informaciòn Quìmica para Emergencias of Argentina. The most recent version is the 2024 edition of the ERG (ERG 2024), titled 2024 Emergency Response Guidebook (ERG2024). The ERG provides essential information about firefighting, spill response, and potential public health effects. For chemicals that are toxic by inhalation (TIH) and chemicals that produce TIH gases upon reaction with water (TIH by water reactivity or TIHWR), the ERG provides initial isolation distances (IIDs) and protective action distances (PADs). The IID defines the radius of the zone around the spill that should be accessed solely by people who are directly involved in emergency response. The PAD is the distance downwind of the source of the release within which persons should be either evacuated or sheltered in place, depending on the severity of the incident and the nature of the population (e.g., density, age, health).

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2024

Rogers Quarry Special Studies Report 2024

Rogers Quarry (RQ) has a history of elevated selenium (Se) concentrations in water and fish caused by inputs from the Y-12 National Security Complex Filled Coal Ash Pond (FCAP). Selenium is acutely toxic at high concentrations, and chronic toxicity occurs at low aqueous concentrations because Se bioaccumulates in fish tissues. The US Environmental Protection Agency (EPA) recently developed water quality criteria for Se that include fish tissue as well as aqueous Se concentrations. The water column concentration criterion is 1.5 µg L -1 for lentic ecosystems and 3.1 µg L -1 for lotic ecosystems. The fish tissue criteria include both an egg/ovary concentration (15.1 µg/g dry weight) and a concentration for whole-body (8.5 µg/g dry weight) or fish muscle (11.3 µg/g dry weight). The egg/ovary criterion supersedes the fillet and aqueous concentrations if measured because Se toxicity manifests via reproductive effects in birds and fish. It is maternally transferred through eggs, leading to teratogenicity (i.e., deformities, developmental effects) in young fish. Historical bioaccumulation data suggest that Se is likely the primary contaminant of concern in RQ, but more recent sampling shows that aqueous As concentrations have been elevated in upper McCoy Branch (MB) leading to RQ. More recently, Se concentrations in fish collected from upper MB were found to be above the tissue criterion for Se for whole-body fish. In FY 2019, actions were taken to deepen the constructed wetland just downstream of the FCAP to increase its ability to remove coal ash particulates from the water column before water enters MB. Sampling was conducted throughout MB in FY 2020-2024 to evaluate the effectiveness of the actions taken in the FCAP wetland and to measure Se concentrations in biota throughout the watershed. The methods and results from a water and fish field collection campaign in April 2024 are presented in this report.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Y-12 National Security Complex Biological Monitoring and Abatement Program—2024 Calendar Year Report

This report provides the results of the CY 2024 sampling of East Fork Poplar Creek (EFPC) as part of the Y-12 National Security Complex (Y-12) Biological Monitoring and Abatement Program (BMAP). The results are presented in the context of historical trends. The Y-12 BMAP was developed in 1985 to demonstrate that the effluent limits established for Y-12 protected the classified uses of the receiving stream, particularly the growth and propagation of aquatic life (Loar et al. 1989). Over the years, the BMAP has become an important and valuable long-term measure of stream conditions resulting from actions and activities at the Y-12 Complex. The BMAP currently consists of three tasks: (1) bioaccumulation monitoring, (2) benthic macroinvertebrate community monitoring, and (3) fish community monitoring. The benthic macroinvertebrate community monitoring task includes studies to evaluate the receiving stream’s biological integrity annually in comparison with Tennessee Water Quality Criteria following Tennessee Department of Environment and Conservation (TDEC) protocols. In addition to presenting the EFPC biological monitoring results, this report includes results from Comprehensive Environmental Response, Compensation, and Liability Act–funded BMAP programs in Bear Creek and McCoy Branch (presented in Appendixes A and B, respectively), as required in the Y-12 National Pollutant Discharge Elimination System (NPDES) permit. Additional biological testing at the Y-12 Complex includes toxicity testing of select storm drains as required in the NPDES permit. Although toxicity testing is not formally part of the BMAP, toxicity testing results from 2024 are provided in Appendix C.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Protein Structure Inspired Discovery of a Novel Inducer of Anoikis in Human Melanoma

Drug discovery historically starts with an established function, either that of compounds or proteins. This can hamper discovery of novel therapeutics. As structure determines function, we hypothesized that unique 3D protein structures constitute primary data that can inform novel discovery. Using a computationally intensive physics-based analytical platform operating at supercomputing speeds, we probed a high-resolution protein X-ray crystallographic library developed by us. For each of the eight identified novel 3D structures, we analyzed binding of sixty million compounds. Top-ranking compounds were acquired and screened for efficacy against breast, prostate, colon, or lung cancer, and for toxicity on normal human bone marrow stem cells, both using eight-day colony formation assays. Effective and non-toxic compounds segregated to two pockets. One compound, Dxr2-017, exhibited selective anti-melanoma activity in the NCI-60 cell line screen. In eight-day assays, Dxr2-017 had an IC50 of 12 nM against melanoma cells, while concentrations over 2100-fold higher had minimal stem cell toxicity. Dxr2-017 induced anoikis, a unique form of programmed cell death in need of targeted therapeutics. Our findings demonstrate proof-of-concept that protein structures represent high-value primary data to support the discovery of novel acting therapeutics. This approach is widely applicable.

Oncology↗