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At least 433 records · Page 24

Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction

BACKGROUND: Opioid addiction is a worldwide public health crisis. In the United States, for example, opioids cause more drug overdose deaths than any other substance. However, opioid addiction treatments have limited efficacy, meaning that additional treatments are needed. METHODS: To help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex of people who died of opioid overdose and control individuals. RESULTS: Here we identified 211 highly interrelated genes identified by genome-wide association studies or dysregulation in the dorsolateral prefrontal cortex of people who died of opioid overdose that implicated the Akt, BDNF (brain-derived neurotrophic factor), and ERK (extracellular signal-regulated kinase) pathways, identifying 414 drugs targeting 48 of these opioid addiction–associated genes. Some of the identified drugs are approved to treat other substance use disorders or depression. CONCLUSIONS: Our synthesis of multiomics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

60 APPLIED LIFE SCIENCES↗

Highly efficient, rapid, and concurrent removal of toxic heavy metals by the novel 2D hybrid LDH–[Sn 2 S 6 ]

According to a United Nations report, by 2050 nearly six billion people worldwide will suffer from clean water scarcity. This is mostly because of the exponential proliferation of world population, urbanization, industrialization, and water pollution. Heavy metals are common water pollutants that can pose grave public health consequences. Existing water purification systems are lack of materials that have the potential for quick, simultaneous, efficient, and cost-efficient removal of numerous toxic metals from wastewater. Here, in this work, we report the design and synthesis of an economically viable Layered Double Hydroxides - Stannic Sulfide, LDH–[Sn 2 S 6 ] that exhibits a rapid, efficient, selective, and concurrent removal of Cu 2+ , Ag + , Cd 2+ , Pb 2+ , and Hg 2+ from parts per million (ppm) level to below 5 parts per billion (ppb) satisfying World Health Organization’s (WHO) safe drinking water limit. Moreover, LDH–[Sn 2 S 6 ] shows exceptionally high removal efficiencies of the above metals in acidic, neutral, and basic conditions. LDH–[Sn 2 S 6 ] also demonstrates enormous sorption capacities of 378, 978, 332, 579, and 666 mg/g for Cu 2+ , Ag + , Cd 2+ , Pb 2+ , and Hg 2+ , respectively. Remarkably, LDH–[Sn 2 S 6 ] displays extraordinary tolerance to the concentrations of Na + , Ca 2+ , Mg 2+ , Cl - , CO 3 2– , NO 3 – ,and SO 4 2- , and other constituents in tap and river water, it efficiently sequestrates Cu 2+ , Ag + , Cd 2+ , Pb 2+ , and Hg 2+ from ppm to safe drinking water levels in minutes. LDH–[Sn 2 S 6 ] shows pseudo-second-order sorption kinetics suggesting chemisorption adsorption mechanism involving M–S bonding. Altogether, the regeneratable LDH–[Sn 2 S 6 ] becomes an exceptional material that shows ultrahigh removal, unprecedented selectivity, rapid adsorption kinetics, wide pH stability, and a massive adsorption capacity. The integration of these features places LDH–[Sn 2 S 6 ] at the top of all adsorbents known to date and thus could be used for wastewater purifications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of PFOS on the behavior, growth, emergence, and predation susceptibility of larval mosquitoes ( Culex quinquefasciatus )

Per-/polyfluoroalkyl substances (PFAS) have been commonly used over several decades for a variety of products and are very persistent in the environment. However, not much is known about their direct effects on aquatic invertebrates and their ecosystems. We examined the survival, behavior, development, and predation susceptibility of mosquito larvae Culex quinquefasciatus exposed to concentrations of perfluorooctanesulfonic acid (PFOS) ranging from 0.02 to 453.7 µg/L. PFOS exposure resulted in reduced larval survival, with a 48 hour LC50 (concentration with 50 % mortality) of 255.99 µg/L. PFOS exposure also resulted in reduced developmental success and slower maturation to adulthood (and thus slower emergence from the water) compared to control larvae. PFOS also resulted in delays in reaction to prodding stimuli, which were meant to simulate a predator attack, and longer reactions to prodding. Larvae exposed to PFOS also spent more time at the bottom of the water column, rather than at the surface where respiration takes place. Effects of larval mosquito PFOS exposure on predation by unexposed damselfly naiads (genus Ischnura) were not detected. Overall, this research suggests that PFOS impacts mosquito larvae survival, behavior, development, and adult emergence, which could have important implications for food webs or public health given the role of mosquitos as disease vectors.

Food web dynamics↗

Comparative life cycle assessment of bioenergy in Japan from residual biomass-based wood pellets produced in the US Pacific Northwest

The US Pacific Northwest (PNW) faces an increase in wildfires due to forest overcrowding and climate change, posing significant environmental and public health risks. Traditional methods of managing surplus biomass, including prescribed burning, have increased air pollution and global warming. While in the PNW, residual woody biomass is being treated as waste, Japan’s growing demand for bio-based energy presents an opportunity to export value-added biomass as energy pellets. This study investigates whether producing wood pellets from the residual woody biomass from forest operations and sawmills for electricity generation in Japan is truly environmentally beneficial. Accordingly, we conducted a cradle-to-grave Life Cycle Assessment (LCA) to evaluate the environmental impact of residual pellets vs. coal for electricity generation. The assessment covered feedstock production, pellet processing, transportation, and combustion phases. Our findings indicate that replacing coal-based electricity in Japan with PNW residual pellet-based electricity can lower the Global Warming Potential (GWP) by about 90% for every unit of electricity displaced. Furthermore, the results show that repurposing the otherwise burnt harvest slash residues for pellet production would improve local air quality by reducing PM 2.5 and smog in the PNW. However, substituting coal with residual pellets marginally increased carcinogenic and ecotoxicity-related emissions. Based on these results, we conclude that substituting coal with residual wood pellets for electricity generation, particularly harvest-slash residual pellets, is environmentally beneficial across most impact categories, including the GWP. This research underscores how an export‑oriented pellet industry can help address the environmental challenges within the regional US wood products industry and global renewable energy supply.

Velappan, Hemalatha [Univ. of Washington, Seattle,↗

Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV)

The high morbidity and mortality associated with SARS-CoV-2 infection, the etiological agent of COVID-19, has had a major impact on global public health. Significant progress has been made in the development of an array of vaccines and biologics, however, the emergence of SARS-CoV-2 variants and breakthrough infections are an ongoing major concern. Furthermore, there is an existing paucity of small-molecule host and virus-directed therapeutics and prophylactics that can be used to counter the spread of SARS-CoV-2, and any emerging and re-emerging coronaviruses. Here, we describe herein our efforts to address this urgent need by focusing on the structure-guided design of potent broad-spectrum inhibitors of SARS-CoV-2 3C-like protease (3CL pro or Main protease), an enzyme essential for viral replication. The inhibitors exploit the directional effects associated with the presence of a gem-dimethyl group that allow the inhibitors to optimally interact with the S4 subsite of the enzyme. Several compounds were found to potently inhibit SARS-CoV-2 and MERS-CoV 3CL proteases in biochemical and cell-based assays. Specifically, the EC50 values of aldehyde 1c and its corresponding bisulfite adduct 1d against SARS-CoV-2 were found to be 12 and 10 nM, respectively, and their CC50 values were >50 μM. Furthermore, deuteration of these compounds yielded compounds 2c/2d with EC50 values 11 and 12 nM, respectively. Replacement of the aldehyde warhead with a nitrile (CN) or an α-ketoamide warhead or its corresponding bisulfite adduct yielded compounds 1g, 1e and 1f with EC50 values 60, 50 and 70 nM, respectively. High-resolution cocrystal structures have identified the structural determinants associated with the binding of the inhibitors to the active site of the enzyme and, furthermore, have illuminated the mechanism of action of the inhibitors. Overall, the high Safety Index (SI) (SI=CC50/EC50) displayed by these compounds suggests that they are well-suited to conducting further preclinical studies.

3-Chymotrypsin-like protease (3CLpro)↗

Different chemical scaffolds bind to L-phe site in Mycobacterium tuberculosis Phe-tRNA synthetase

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mt), is one of the deadliest infectious diseases. The rise of multidrug-resistant strains represents a major public health threat, requiring new therapeutic options. Bacterial aminoacyl-tRNA synthetases (aaRS) have been shown to be highly promising drug targets, including for TB treatment. These enzymes play an essential role in translating the DNA gene code into protein sequence by attaching specific amino acid to their cognate tRNAs. They have multiple binding sites that can be targeted for inhibitor discovery: amino acid binding pocket, ATP binding pocket, tRNA binding site and an editing domain. Recently we reported several high-resolution structures of M. tuberculosis phenylalanyl-tRNA synthetase (MtPheRS) complexed with tRNA Phe and either L-Phe or a nonhydrolyzable phenylalanine adenylate analog. Here, in this study, using Nucleic Magnetic Resonance (NMR) and Surface Plasmon Resonance (SPR) we identified fragments that bind to MtPheRS and we determined crystal structures of their complexes with MtPheRS/tRNA Phe . All the binders interact with the L-Phe amino acid binding site. The analysis of interactions of the new compounds combined with adenylate analog structure provides insights for the rational design of antituberculosis drugs. The 3 ' arm of the tRNA Phe in all the structures was disordered with exception of one complex with D-735 compound. In this structure the 3' CCA end of the acceptor stem is observed in the editing domain of MtPheRS providing insights regarding the post-transfer editing activity of class II aaRS.

Gade, Priyanka [Univ. of Chicago, IL (United State↗

Hurricanes and turbulent floods threaten arsenic-contaminated coastal soils and vulnerable communities

Coastal environments, particularly those adjacent to Superfund sites, are at increased risk of contaminant release during natural disasters, posing serious threats to nearby communities. To investigate this issue, we employed an advanced laboratory flood simulator to impose arsenic-contaminated sediments to turbulent flooding events. We further monitored changes in arsenic collocation and solid-phase speciation using advanced synchrotron radiation-based techniques to understand the impacts of flooding on arsenic mobility. Our results demonstrate that turbulent conditions significantly enhance the resuspension of arsenic-rich sediments, resulting in increased arsenic release into the water. This mobilization is driven by the erosion of the reduced sediments and the redox-mediated transformation and dissolution of Fe and Mn (oxyhydr) oxides, which promote the release of As(III). We found that arsenic speciation on resuspended particles is closely tied to shear stress, with As(V) prevailing at low stress and the more toxic As(III) dominating at higher stress levels. In the post-erosion phase, solid-phase As(III) decreased while dissolved As(III) increased, indicating ongoing desorption. The persistence of multiple arsenic species on resuspended particles marks them as potential long-range transport vectors. Thus, the environmental impact of flooding and sediment resuspension extends beyond the event itself, raising longer-term concerns for arsenic mobility. Our comprehensive geospatial analysis revealed substantial overlap between arsenic-contaminated soils and regions at high risk of flooding and hurricanes across the conterminous United States. This overlap disproportionately impacts economically disadvantaged and marginalized communities. Approximately 40 million Americans reside within 10 kilometers of these high-risk contaminated zones, with nearly 28 million exposed to hurricane threats and around 18 million vulnerable to flooding risks. Alarmingly, over 40% of those affected by hurricanes and 33% of those impacted by flooding belong to underrepresented minority and low-income populations. These findings highlight the urgent need for targeted mitigation strategies to protect public health and address environmental justice concerns.

54 ENVIRONMENTAL SCIENCES↗

Using deep transfer learning and satellite imagery to estimate urban air quality in data-poor regions

Urban air pollution is a critical public health challenge in low-and-middle-income countries (LMICs). At the same time, LMICs tend to be data-poor, lacking adequate infrastructure to monitor air quality (AQ). As LMICs undergo rapid urbanization, the socio-economic burden of poor AQ will be immense. Here we present a globally scalable two-step deep learning (DL) based approach for AQ estimation in LMIC cities that mitigates the need for extensive AQ infrastructure on the ground. We train a DL model that can map satellite imagery to AQ in high-income countries (HICs) with sufficient ground data, and then adapt the model to learn meaningful AQ estimates in LMIC cities using transfer learning. The trained model can explain up to 54% of the variation in the AQ distribution of the target LMIC city without the need for target labels. The approach is demonstrated for Accra in Ghana, Africa, with AQ patterns learned and adapted from two HIC cities, specifically Los Angeles and New York.

54 ENVIRONMENTAL 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↗

CFD modeling of non-catalytic, partial-oxidation engine reformer for flare mitigation

Flaring associated natural gas is commonly employed in the oil and gas industry to reduce methane (CH 4 ) emissions but generates carbon dioxide (CO 2 ) and harmful pollutants, significantly contributing to air pollution and posing risks to public health. To mitigate this impact, M2X Energy Inc. has developed a small-scale, modular gas-to-methanol system. This system features an engine reformer that performs fuel-rich partial oxidation of wellhead gas to produce syngas—a mixture of carbon monoxide (CO) and hydrogen (H 2 )—followed by a downstream reactor for methanol synthesis. This study focused on computational fluid dynamics (CFD) modeling of the engine reformer to simulate partial oxidation chemistry, predict the rich-burn operating limit, and assess syngas quality, ultimately aiding in design and operational optimization. The CFD model, developed within a Reynolds-Averaged Navier-Stokes (RANS) turbulence framework, incorporated sub-models for turbulent combustion, a chemical mechanism with polycyclic aromatic hydrocarbon (PAH) pathways, and soot emissions to accurately capture the fuel-rich, turbulent jet ignition and combustion processes. Model validation against experimental data showed good agreement across pre- and main-chamber pressures, apparent heat release rates, and exhaust gas concentrations of key species (H 2 , CO, CO 2 , CH 4 ) for varying intake equivalence ratios. Here, the model identified a rich-burn operating limit near a fuel-air equivalence ratio of 2.35, consistent with experimental observations. Furthermore, syngas quality analysis revealed that extending the rich-burn limit through engine reformer optimization could enhance syngas production, contributing to higher methanol synthesis efficiency.

Computational Fluid Dynamics↗

An Evaluation of the Global Effects of Tritium Emissions from Nuclear Fusion Power

We report that tritium, like all hydrogen isotopes, is difficult to confine and easily diffuses through most materials. As currently planned, fusion power plants will process and handle large quantities of deuterium and tritium as fuel, and therefore, will become sources of tritium input into the environment. Tritium releases from a worldwide distribution of tritium sources (fusion or fission) will lead to higher tritium levels overall and have global impact. This report investigates the hydrologic partitioning of yearly tritium releases assuming 1 g/yr loss per 500 MW of nuclear power generation for varying scales of power generation. On large scales, it is found that the worldwide average levels of tritium could exceed some public health goals and regulatory guidelines. Tritium concentrations at such levels may also have other impacts on the environment through increased ion-pair generation.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Zeolite-templated carbons as effective sorbents to remove methylsiloxanes and derivatives: A computational screening

Though widely used in our daily lives, volatile methylsiloxanes and derivatives are emerging contaminants and becoming a high-priority environment and public health concern. Developing effective sorbent materials can remove siloxanes in a cost-effective manner. Herein, by means of Grand Canonical Monte Carlo (GCMC) simulations, we evaluated the potentials of the recently proposed 68 stable zeolite-templated carbons (ZTCs) for the removal of four linear methylsiloxanes and derivatives as well as two cyclic methylsiloxanes by the calculated average loading and average adsorption energy values. Four ZTCs, namely ISV, FAU1, FAU3, and H8326836, were identified with the top 50% adsorption performance toward all the six targeted contaminants, which outperform activated carbons. Further first principles computations revealed that steric hindrance, electrostatic interactions (further enhanced by charge transfer), and CH-π interactions account for the outstanding adsorption performance of these ZTCs. This work provides a quick procedure to computationally screen promising ZTCs for siloxane removal, and help guide future experimental and theoretical investigations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The Western Lake Erie culture collection: A promising resource for evaluating the physiological and genetic diversity of Microcystis and its associated microbiome

Cyanobacterial harmful algal blooms (cyanoHABs) dominated by Microcystis spp. have significant public health and economic implications in freshwater bodies around the world. These blooms are capable of producing a variety of cyanotoxins, including microcystins, that affect fishing and tourism industries, human and environmental health, and access to drinking water. In this study, we isolated and sequenced the genomes of 21 primarily unialgal Microcystis cultures collected from western Lake Erie between 2017 and 2019. While some cultures isolated in different years have a high degree of genetic similarity (genomic Average Nucleotide Identity >99%), genomic data show that these cultures also represent much of the breadth of known Microcystis diversity in natural populations. Only five isolates contained all the genes required for microcystin biosynthesis while two isolates contained a previously described partial mcy operon. Microcystin production within cultures was also assessed using Enzyme-Linked Immunosorbent Assay (ELISA) and supported genomic results with high concentrations (up to 900 μg L⁻¹) in cultures with complete mcy operons and no or low toxin detected otherwise. These xenic cultures also contained a substantial diversity of bacteria associated with Microcystis, which has become increasingly recognized as an essential component of cyanoHAB community dynamics. These results highlight the genomic diversity among Microcystis strains and associated bacteria in Lake Erie, and their potential impacts on bloom development, toxin production, and toxin degradation. Furthermore, this culture collection significantly increases the availability of environmentally relevant Microcystis strains from temperate North America.

CyanoHABs↗

A missing layer in COVID-19 studies: Transmission of enveloped viruses in mucus-rich droplets

Here we evaluate the influence of mucus layers on the evaporation time and transport of enveloped viruses, including SARS-CoV-2. Enveloped viruses must remain moist to be fully infective. Yet, the Wells model based on water droplets divides respiratory droplets into either quickly evaporated aerosolized particles termed droplet nuclei (<10 s) or liquid droplets that fall to the nearest surface, leaving no physical mechanism for airborne transmission of fully infective enveloped viruses over large distances (greater than a few meters). Yet, the role of mucus layers on evaporation times has not been considered even though the formation of mucus shells around liquid cores of respiratory droplets has been shown experimentally. Here we show that mucus shells increase the drying time by orders of magnitude so that enveloped virions may remain well hydrated and, thus, fully infective at substantial distances. Further, this provides a mechanism by which infective enveloped virus particles can transmit as aerosols within buildings and between buildings over extended distances. This analysis is important because public health agencies typically follow the Wells model to establish health policies including social/physical distancing guidelines.

60 APPLIED LIFE SCIENCES↗

Achieving an 80% carbon-free electricity system in China by 2035

Dramatic reductions in solar, wind, and battery storage costs create new opportunities to reduce emissions and costs in China’s electricity sector, beyond current policy goals. This study examines the cost, reliability, emissions, public health, and employment implications of increasing the share of non-fossil fuel (“carbon free”) electricity generation in China to 80% by 2035. The analysis uses state-of-the-art modeling with high resolution load, wind, and solar inputs. The study finds that achieving an 80% carbon free electricity system in China by 2035 could reduce wholesale electricity costs, relative to a current policy baseline, while maintaining high levels of reliability, reducing deaths from air pollution, and increasing employment. In our 80% scenario, wind and solar generation capacity reach 3 TW and battery storage capacity reaches 0.4 TW by 2035, implying a rapid scale up in these resources that will require changes in policy targets, markets and regulation, and land use policies.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Anion-exchanged and quaternary ammonium functionalized MIL-101-Cr metal-organic framework (MOF) for ReO 4 – /TcO 4 – sequestration from groundwater

There are few effective technologies for the sequestration of highly water-soluble pertechnetate (TcO 4 – ) from contaminated water despite the urgency of environmental and public health concerns. Here, anion exchanged and cetyltrimethylammonium bromide (CTAB) functionalized MIL-101-Cr-NO 3 were investigated for perrhenate (ReO 4 – ), a surrogate of TcO 4 – , sequestration from artificial groundwater. Cl – , I – , and CF 3 SO 3 – exchanged MIL-101-Cr proved more effective at ReO 4 – removal than the parent MIL-101-Cr-F. Compared to the parent framework, CTAB functionalized MIL-101-Cr-NO 3 increased ReO 4 – removal capacity from 39 to 139 mg/g, improved the reaction kinetics from ~30 to <10 min to reach full adsorption capacity and the selectivity for ReO 4 – over competing NO 3 – , CO 3 2– , SO 4 2– , and Cl – . Spectroscopic data indicated that the chemical speciation of Re in the exchanged MIL-101-Cr remained ReO 4 – , indicating synergistic sequestration through both anion exchange and non-ion exchange binding with the positively charged ligand of CTAB. These studies foreshadow potential applications of MOFs for the remediation of 99 TcO 4 – from contaminated environments.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Nuclear waste Educator's workshop: What and how do we teach about nuclear waste?

A workshop was held at the Massachusetts Institute of Technology (MIT) on July 25th and 26th, 2022. The objective was to develop a blueprint for educating next-generation engineers and scientists about nuclear waste management and disposal, which requires knowledge from diverse disciplines, including nuclear, chemical, civil, environmental, and geological science and engineering. The 49 participants included university professors, researchers, industry experts, and government officials from different areas. First, we have developed a list of key fundamental knowledge on waste management and disposal across the nuclear fuel cycle. In addition, we discussed strategies on how to teach students with diverse backgrounds through innovative teaching strategies as well as how to attract students into this area. Through the workshop, we identified the critical needs to (1) develop community resources for nuclear waste education; (2) synthesize historical perspectives, including past contamination and the management of general hazardous waste; (3) emphasize a complete life-cycle perspective, including proper waste management as the key component for energy sustainability; (4) teach students how to communicate about the key facts and risks to technical and non-technical audiences; and (5) accelerate the use of the state-of-art-technologies to attract and retain a young workforce. Furthermore, we aim to build a diverse, inclusive community that supports students in developing their own narratives about nuclear waste, particularly in recognizing that antagonistic views have been important to improving safety and protecting public health and the environment.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗