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At least 991 records · Page 55

Activation of G Protein-Coupled Receptor Kinase 1 Involves Interactions between Its N-Terminal Region and Its Kinase Domain

G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors (GPCRs) to initiate receptor desensitization. In addition to the canonical phosphoacceptor site of the kinase domain, activated receptors bind to a distinct docking site that confers higher affinity and activates GRKs allosterically. Recent mutagenesis and structural studies support a model in which receptor docking activates a GRK by stabilizing the interaction of its 20-amino acid N-terminal region with the kinase domain. This interaction in turn stabilizes a closed, more active conformation of the enzyme. To investigate the importance of this interaction for the process of GRK activation, we first validated the functionality of the N-terminal region in rhodopsin kinase (GRK1) by site-directed mutagenesis and then introduced a disulfide bond to cross-link the N-terminal region of GRK1 with its specific binding site on the kinase domain. Characterization of the kinetic and biophysical properties of the cross-linked protein showed that disulfide bond formation greatly enhances the catalytic efficiency of the peptide phosphorylation, but receptor-dependent phosphorylation, Meta II stabilization, and inhibition of transducin activation were unaffected. These data indicate that the interaction of the N-terminal region with the kinase domain is important for GRK activation but does not dictate the affinity of GRKs for activated receptors.

59 BASIC BIOLOGICAL SCIENCES↗

OPERA models for predicting physicochemical properties and environmental fate endpoints

The collection of chemical structure information and associated experimental data for quantitative structure–activity/ property relationship (QSAR/QSPR) modeling is facilitated by an increasing number of public databases containing large amounts of useful data. However, the performance of QSAR models highly depends on the quality of the data and modeling methodology used. This study aims to develop robust QSAR/QSPR models for chemical properties of environmental interest that can be used for regulatory purposes. This study primarily uses data from the publicly available PHYSPROP database consisting of a set of 13 common physicochemical and environmental fate properties. These datasets have undergone extensive curation using an automated workflow to select only high-quality data, and the chemical structures were standardized prior to calculation of the molecular descriptors. The modeling procedure was developed based on the five Organization for Economic Cooperation and Development (OECD) principles for QSAR models. A weighted k-nearest neighbor approach was adopted using a minimum number of required descriptors calculated using PaDEL, an open-source software. The genetic algorithms selected only the most pertinent and mechanistically interpretable descriptors (2–15, with an average of 11 descriptors). The sizes of the modeled datasets varied from 150 chemicals for biodegradability half-life to 14,050 chemicals for logP, with an average of 3222 chemicals across all endpoints. The optimal models were built on randomly selected training sets (75%) and validated using fivefold cross-validation (CV) and test sets (25%). The CV Q2 of the models varied from 0.72 to 0.95, with an average of 0.86 and an R2 test value from 0.71 to 0.96, with an average of 0.82. Modeling and performance details are described in QSAR model reporting format and were validated by the European Commission’s Joint Research Center to be OECD compliant. All models are freely available as an open-source, command-line application called OPEn structure–activity/property Relationship App (OPERA). OPERA models were applied to more than 750,000 chemicals to produce freely available predicted data on the U.S. Environmental Protection Agency’s CompTox Chemistry Dashboard.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

No more active galactic nuclei in clumpy disks than in smooth galaxies at z ∼ 2 in CANDELS/3D-HST

We use CANDELS imaging, 3D-HST spectroscopy, and Chandra X-ray data to investigate if active galactic nuclei (AGNs) are preferentially fueled by violent disk instabilities funneling gas into galaxy centers at 1.3 < z < 2.4. We select galaxies undergoing gravitational instabilities using the number of clumps and degree of patchiness as proxies. The CANDELS visual classification system is used to identify 44 clumpy disk galaxies, along with mass-matched comparison samples of smooth and intermediate morphology galaxies. We note that despite being mass-matched and having similar star formation rates, the smoother galaxies tend to be smaller disks with more prominent bulges compared to the clumpy galaxies. The lack of smooth extended disks is probably a general feature of the z ∼ 2 galaxy population, and means we cannot directly compare with the clumpy and smooth extended disks observed at lower redshift. We find that z ∼ 2 clumpy galaxies have slightly enhanced AGN fractions selected by integrated line ratios (in the mass-excitation method), but the spatially resolved line ratios indicate this is likely due to extended phenomena rather than nuclear AGNs. Meanwhile, the X-ray data show that clumpy, smooth, and intermediate galaxies have nearly indistinguishable AGN fractions derived from both individual detections and stacked non-detections. The data demonstrate that AGN fueling modes at z ∼ 1.85—whether violent disk instabilities or secular processes—are as efficient in smooth galaxies as they are in clumpy galaxies.

79 ASTRONOMY AND ASTROPHYSICS↗

Measurements of the time-dependent cosmic-ray Sun shadow with seven years of IceCube data: Comparison with the Solar cycle and magnetic field models

Observations of the time-dependent cosmic-ray Sun shadow have been proven as a valuable diagnostic for the assessment of solar magnetic field models. Here, seven years of IceCube data are compared to solar activity and solar magnetic field models. A quantitative comparison of solar magnetic field models with IceCube data on the event rate level is performed for the first time. Additionally, a first energy-dependent analysis is presented and compared to recent predictions. We use seven years of IceCube data for the moon and the Sun and compare them to simulations on data rate level. The simulations are performed for the geometrical shadow hypothesis for the moon and the Sun and for a cosmic-ray propagation model governed by the solar magnetic field for the case of the Sun. We find that a linearly decreasing relationship between Sun shadow strength and solar activity is preferred over a constant relationship at the 6.4σ level. We test two commonly used models of the coronal magnetic field, both combined with a Parker spiral, by modeling cosmic-ray propagation in the solar magnetic field. Both models predict a weakening of the shadow in times of high solar activity as it is also visible in the data. We find tensions with the data on the order of 3σ for both models, assuming only statistical uncertainties. The magnetic field model CSSS fits the data slightly better than the PFSS model. This is generally consistent with what is found previously by the Tibet AS-γ Experiment; a deviation of the data from the two models is, however, not significant at this point. Regarding the energy dependence of the Sun shadow, we find indications that the shadowing effect increases with energy during times of high solar activity, in agreement with theoretical predictions.

79 ASTRONOMY AND ASTROPHYSICS↗

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

60 APPLIED LIFE SCIENCES↗

Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: The dalcetrapib experience

Introduction: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. Methods: Liver samples were obtained from ∼ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. Results: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5–1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day). Discussion: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay. -- Highlights: ► Liver tumors were induced in male mice by dalcetrapib in a 2-y study (bioassay). ► Cyp2b10 induction typifies activation of nuclear receptor CAR in mouse liver. ► First report of hepatic Cyp2b10 monitoring at the end of a mouse bioassay. ► Cyp2b10 induction supports CAR activation by dalcetrapib in mouse bioassay. ► CAR activation is a mechanism of hepatic tumorigenesis of no relevance to humans.

60 APPLIED LIFE SCIENCES↗

THE COLD SHOULDER: EMISSION MEASURE DISTRIBUTIONS OF ACTIVE REGION CORES

The coronal heating mechanism for active region core loops is difficult to determine because these loops are often not resolved and cannot be studied individually. Rather, we concentrate on the 'inter-moss' areas between loop footpoints. We use observations from the Hinode EUV Imaging Spectrometer and the X-Ray Telescope to calculate the emission measure distributions of eight inter-moss areas in five different active regions. The combined data sets provide both high- and low-temperature constraints and ensure complete coverage in the temperature range appropriate for active regions. For AR 11113, the emission can be modeled with heating events that occur on timescales less than the cooling time. The loops in the core regions appear to be close to equilibrium and are consistent with steady heating. The other regions studied, however, appear to be dominated by nanoflare heating. Our results are consistent with the idea that active region age is an important parameter in determining whether steady or nanoflare heating is primarily responsible for the core emission, that is, older regions are more likely to be dominated by steady heating, while younger regions show more evidence of nanoflares.

79 ASTRONOMY AND ASTROPHYSICS↗

Random mitotic activities across human embryonic stem cell colonies.

A systemic and quantitative study was performed to examine whether different levels of mitotic activities, assessed by the percentage of S-phase cells at any given time point, existed at different physical regions of human embryonic stem (hES) cell colonies at 2, 4, 6 days after cell passaging. Mitotically active cells were identified by the positive incorporation of 5-bromo-2-deoxyuridine (BrdU) within their newly synthesized DNA. Our data indicated that mitotically active cells were often distributed as clusters randomly across the colonies within the examined growth period, presumably resulting from local deposition of newly divided cells. This latter notion was further demonstrated by the confined growth of enhanced green florescence protein (EGFP) expressing cells amongst non-GFP expressing cells. Furthermore, the overall percentage of mitotically active cells remained constantly at about 50% throughout the 6-day culture period, indicating mitotic activities of hES cell cultures were time-independent under current growth conditions.

59 BASIC BIOLOGICAL SCIENCES↗

Quality Assurance Project Plan for Closure of the Central Facilities Area Sewage Treatment Plant Lagoon 3 and Land Application Area

This quality assurance project plan describes the technical requirements and quality assurance activities of the environmental data collection/analyses operations to close Central Facilities Area Sewage treatment Plant Lagoon 3 and the land application area. It describes the organization and persons involved, the data quality objectives, the analytical procedures, and the specific quality control measures to be employed. All quality assurance project plan activities are implemented to determine whether the results of the sampling and monitoring performed are of the right type, quantity, and quality to satisfy the requirements for closing Lagoon 3 and the land application area.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Initial Efforts Organizing WPNCS SG-8: Preservation of Expert Knowledge and Judgement Applied to Criticality Benchmarks

The Working Party on Nuclear Criticality Safety (WPNCS) under the guidance of the Organization for Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) has over 20 years of experience addressing concerns related to static and transient configurations encountered within the nuclear fuel cycle: fuel fabrication, transportation, reprocessing, storage, and geological disposal. One of the cornerstone activities of the WPNCS is the International Criticality Safety Benchmark Evaluation Project (ICSBEP), which was established to identify a comprehensive set of criticality benchmark data, evaluate the data, including quantification of overall uncertainties; compile the data into a standardized format, perform sample calculations utilizing modern nuclear data sets and codes utilized in nuclear criticality safety, and formally document the work into a single source of verified benchmark data. Annually, members of the ICSBEP Technical Review Group (TRG) contribute evaluated benchmark data that undergoes comprehensive technical review prior to publication in the ICSBEP Handbook. In the years since the ICSBEP was established, there has been much work to prepare benchmark data to support validation activities in nuclear criticality safety. The 2020 edition of the ICSBEP Handbook contains acceptable benchmark specifications for 5,053 critical, subcritical, or near-critical configurations in 582 benchmark evaluations. Modern benchmark development benefits from decades of experienced international participants, a well-established handbook format, supplementary guides to deal with uncertainty quantification, and a comprehensive review process based upon independent reviews from international experts. The ICSBEP Handbook also contains 838 configurations deemed unacceptable to support criticality safety efforts. They are recorded, with the reasoning for their rejection, to preserve the experimental data, prevent reevaluation of data that are incomplete or contain known errors, and/or to potentially allow future reevaluation of the experiment pending the identification of sufficient data to resolve identified inconsistencies and errors. Users of the ICSBEP Handbook today might notice that the rigor and quality of modern criticality safety benchmarks is much greater than those prepared within the initial decade of the project. Benchmarks with 1s uncertainties in k eff greater than 1% were traditionally rejected unless they were identified as unique experiment types that encompassed materials, fuels, or designs not available from other benchmark experiments. However, benchmarks developed using modern experimental techniques and practices typically have uncertainties on the order of a few tenths of a percent. There have been ongoing efforts to improve the overall quality of previously published benchmark evaluations. Seventy-eight evaluations, containing approximately 600 configurations, have been revised just within the past decade. An additional eleven benchmarks are under revision for updated release in the 2020 edition of the ICSBEP Handbook. If some of the historic benchmarks were resubmitted in their current form to the TRG today, they would be rejected due to lack of data, missing components in the uncertainty analysis, or incomplete benchmark model development. The use of historic criticality safety benchmarks that underestimate the total uncertainty, lack properly quantified biases, or provide inadequate benchmark specifications do not sufficiently support modern criticality safety and nuclear data efforts. Although the ICSBEP Handbook is recognized by regulating bodies to support criticality safety, users are required to justify their reasons to ignore historic benchmark data and include additional safety margins within their designs. Discussions were held at the WPNCS 23rd Annual Meeting in September 2019 regarding the aforementioned issues. The resultant decision was to establish Subgroup 8 (SG-8): Preservation of Expert Knowledge and Judgement Applied to Criticality Benchmarks. The current activities of SG-8 are discussed herein.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae

The crystal structure of 5-hydroxyisourate hydrolase from K. pneumoniae and the steady-state kinetic parameters of the native enzyme as well as several mutants provide insights into the catalytic mechanism of this enzyme and the possible roles of the active-site residues. The stereospecific oxidative degradation of uric acid to (S)-allantoin has recently been demonstrated to proceed via two unstable intermediates and requires three separate enzymatic reactions. The second step of this reaction, the conversion of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, is catalyzed by HIU hydrolase (HIUH). The high-resolution crystal structure of HIUH from the opportunistic pathogen Klebsiella pneumoniae (KpHIUH) has been determined. KpHIUH is a homotetrameric protein that, based on sequence and structural similarity, belongs to the transthyretin-related protein family. In addition, the steady-state kinetic parameters for this enzyme and four active-site mutants have been measured. These data provide valuable insight into the functional roles of the active-site residues. Based upon the structural and kinetic data, a mechanism is proposed for the KpHIUH-catalyzed reaction.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

The inherent tensions arising from attempting to carry out strategic environmental assessments on all policies, plans and programmes

This paper evaluates the tensions that result from routinely applying SEA to all policies, plans and programmes within Scotland. The European Union SEA Directive, effective in many EU member states from 2004, introduced a requirement for environmental assessment of certain plans and programmes. Scotland, a devolved nation within the EU member state of the United Kingdom, aimed to be a &#x27;world leader in SEA&#x27; by legislating for SEA to be undertaken of all public sector plans, programmes and strategies, with the word &#x27;strategies&#x27; being equated with &#x27;policies&#x27;. This paper presents detailed data regarding Scottish SEA activity between 2004 and 2007, including responses to consultations on SEA reports. This empirical research found that, reflecting a general difficulty in determining where and when SEA should be applied, engagement with the SEA process was not as widespread as intended (including the pre-screening and screening stages). Eight tensions evident from Scotland&#x27;s application of SEA are identified, and their broader relevance is examined. - Highlights: Black-Right-Pointing-Pointer We examine detailed data regarding Scottish strategic environmental assessment (SEA) activity. Black-Right-Pointing-Pointer There is a general difficulty in determining where SEA should be applied. Black-Right-Pointing-Pointer Engagement with the SEA process was not as widespread as intended. Black-Right-Pointing-Pointer Eight &#x27;tensions&#x27; that question the efficacy of applying SEA to all plans, programmes and policies were identified.

54 ENVIRONMENTAL SCIENCES↗

Medium-Chain Fatty Acid Synthesis by “ Candidatus Weimeria bifida” gen. nov., sp. nov., and “ Candidatus Pseudoramibacter fermentans” sp. nov.

ABSTRACT Chain elongation is emerging as a bioprocess to produce valuable medium-chain fatty acids (MCFA; 6 to 8 carbons in length) from organic waste streams by harnessing the metabolism of anaerobic microbiomes. Although our understanding of chain elongation physiology is still evolving, the reverse β-oxidation pathway has been identified as a key metabolic function to elongate the intermediate products of fermentation to MCFA. Here, we describe two uncultured chain-elongating microorganisms that were enriched in an anaerobic microbiome transforming the residues from a lignocellulosic biorefining process. Based on a multi-omic analysis, we describe “ Candidatus Weimeria bifida” gen. nov., sp. nov., and “ Candidatus Pseudoramibacter fermentans” sp. nov., both predicted to produce MCFA but using different substrates. The analysis of a time series metatranscriptomic data set suggests that “ Ca . Weimeria bifida” is an effective xylose utilizer since both the pentose phosphate pathway and the bifid shunt are active. Furthermore, the metatranscriptomic data suggest that energy conservation during MCFA production in this organism is essential and occurs via the creation of an ion motive force using both the RNF complex and an energy-conserving hydrogenase. For “ Ca . Pseudoramibacter fermentans,” predicted to produce MCFA from lactate, the metatranscriptomic analysis reveals the activity of an electron-confurcating lactate dehydrogenase, energy conservation via the RNF complex, H 2 production for redox balance, and glycerol utilization. A thermodynamic analysis also suggests the possibility of glycerol being a substrate for MCFA production by “ Ca . Pseudoramibacter fermentans.” In total, this work reveals unknown characteristics of MCFA production in two novel organisms. IMPORTANCE Chain elongation by medium-chain fatty acid (MCFA)-producing microbiomes offers an opportunity to produce valuable chemicals from organic streams that would otherwise be considered waste. However, the physiology and energetics of chain elongation are only beginning to be studied, and many of these organisms remain uncultured. We analyzed MCFA production by two uncultured organisms that were identified as the main MCFA producers in a microbial community enriched from an anaerobic digester; this characterization, which is based on meta-multi-omic analysis, complements the knowledge that has been acquired from pure-culture studies. The analysis revealed previously unreported features of the metabolism of MCFA-producing organisms.

59 BASIC BIOLOGICAL SCIENCES↗

Antiviral discovery using sparse datasets by integrating experiments, molecular simulations, and machine learning

Computational methods have demonstrated success in identifying virucidal agents, effectively contributing to the discovery of novel virucidal molecules. In this study, we developed a machine learning (ML) model, trained on a small dataset, to predict inhibitors of human enterovirus 71 (EV71), a pathological agent that causes severe disease in children and immunocompromised adults. Despite the dataset’s limitation, comprising of only 36 compounds tested, our ML framework demonstrated significant predictive capability. Notably, experimental validation revealed that five out of the eight compounds predicted by our model from the Chinese cosmetic material list exhibited virucidal activity. The inhibitor effects displayed by the main active compounds were further confirmed by molecular dynamics simulation. This underscores the potential of our AI-driven approach to bypass data constraints in identifying active molecules against viral pathogens.

60 APPLIED LIFE SCIENCES↗

THE SLOAN DIGITAL SKY SURVEY DATA RELEASE 7 SPECTROSCOPIC M DWARF CATALOG. III. THE SPATIAL DEPENDENCE OF MAGNETIC ACTIVITY IN THE GALAXY

We analyze the magnetic activity of 59,318 M dwarfs from the Sloan Digital Sky Survey Data Release 7. This analysis explores the spatial distribution of M dwarf activity as a function of both vertical distance from the Galactic plane (Z) and planar distance from the Galactic center (R). We confirm the established trends of decreasing magnetic activity (as measured by H{alpha} emission) with increasing distance from the mid-plane of the disk and find evidence of a trend in Galactocentric radii. We measure a non-zero radial gradient in the activity fraction in our analysis of stars with spectral types dM3 and dM4. The activity fraction increases with R and can be explained by a decreasing mean stellar age with increasing distance from the Galactic center.

79 ASTRONOMY AND ASTROPHYSICS↗

The characterization of the distant blazar GB6 J1239+0443 from flaring and low activity periods

In 2008, AGILE and Fermi detected gamma-ray flaring activity from the unidentified EGRET source 3EG J1236+0457, recently associated with a flat spectrum radio quasar (GB6 J1239+0443) at z = 1.762. The optical counterpart of the gamma-ray source underwent a flux enhancement of a factor of 15–30 in six years, and of ~10 in six months. Here, we interpret this flare-up in terms of a transition from an accretion-disc-dominated emission to a synchrotron-jet-dominated one. We analysed a Sloan Digital Sky Survey (SDSS) archival optical spectrum taken during a period of low radio and optical activity of the source. We estimated the mass of the central black hole using the width of the C iv emission line. In our work, we have also investigated SDSS archival optical photometric data and ultraviolet GALEX observations to estimate the thermal disc emission contribution of GB6 J1239+0443. This analysis of the gamma-ray data taken during the flaring episodes indicates a flat gamma-ray spectrum, with an extension of up to 15 GeV, with no statistically relevant sign of absorption from the broad-line region, suggesting that the blazar zone is located beyond the broad-line region. Our result is confirmed by the modelling of the broad-band spectral energy distribution (well constrained by the available multiwavelength data) of the flaring activity periods and by the accretion disc luminosity and black hole mass estimated by us using archival data.

79 ASTRONOMY AND ASTROPHYSICS↗

Corrective Action Decision Document for Corrective Action Unit 562: Waste Systems Nevada Test Site, Nevada, Revision 0

This Corrective Action Decision Document (CADD) presents information supporting the selection of corrective action alternatives (CAAs) leading to the closure of Corrective Action Unit (CAU) 562, Waste Systems, in Areas 2, 23, and 25 of the Nevada Test Site, Nevada. This complies with the requirements of the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. Corrective Action Unit 562 comprises the following corrective action sites (CASs): • 02-26-11, Lead Shot • 02-44-02, Paint Spills and French Drain • 02-59-01, Septic System • 02-60-01, Concrete Drain • 02-60-02, French Drain • 02-60-03, Steam Cleaning Drain • 02-60-04, French Drain • 02-60-05, French Drain • 02-60-06, French Drain • 02-60-07, French Drain • 23-60-01, Mud Trap Drain and Outfall • 23-99-06, Grease Trap • 25-60-04, Building 3123 Outfalls The purpose of this CADD is to identify and provide the rationale for the recommendation of CAAs for the 13 CASs within CAU 562. Corrective action investigation (CAI) activities were performed from July 27, 2009, through May 12, 2010, as set forth in the CAU 562 Corrective Action Investigation Plan. The purpose of the CAI was to fulfill the following data needs as defined during the data quality objective (DQO) process: • Determine whether COCs are present. • If COCs are present, determine their nature and extent. • Provide sufficient information and data to complete appropriate corrective actions. A data quality assessment (DQA) performed on the CAU 562 data demonstrated the quality and acceptability of the data for use in fulfilling the DQO data needs. Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the COCs for each CAS. The results of the CAI identified COCs at 10 of the 13 CASs in CAU 562, and thus corrective action is required. Assessment of the data generated from investigation activities conducted at CAU 562 is shown in Table ES-1. Based on the evaluation of analytical data from the CAI, review of future and current operations at the 13 CASs, and the detailed and comparative analysis of the potential CAAs, the following corrective actions are recommended for CAU 562. • No further action is the preferred corrective action for CASs 02-60-01, 02-60-06, and 02-60-07. • Clean closure is the preferred corrective action for CASs 02-26-11, 02-44-02, 02-59-01, 02-60-02, 02-60-03, 02-60-04, 02-60-05, 23-60-01, 23-99-06, and 25-60-04. The preferred CAAs were evaluated on technical merit focusing on performance, reliability, feasibility, safety, and cost. The alternatives were judged to meet all requirements for the technical components evaluated. The alternatives meet all applicable federal and state regulations for closure of the site and will reduce potential exposures to contaminated media to acceptable levels. The DOE, National Nuclear Security Administration Nevada Site Office provides the following recommendations: • No further corrective action is required at CASs 02-60-01, 02-60-06, and 02-60-07. • Clean closure is recommended for the remaining 10 CASs in CAU 562. • A Corrective Action Plan will be submitted to the Nevada Division of Environmental Protection that contains a detailed description of the proposed actions that will be taken to implement the selected corrective actions.

54 ENVIRONMENTAL SCIENCES↗