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At least 1,009 records · Page 56

Integration and commissioning plan of Full Flow Purifier at Muon Campus

The Full Flow Purifier for Fermilab's Muon Campus uses a charcoal bed surrounded by a liquid nitrogen jacket to purify up to 240 g/s of helium gas. Fabrication by Ability Engineering Technology Inc. has been completed and the purifier delivered to Fermilab. It is the largest purifier to be used at Fermilab based on both capacity and size. A previous paper discussed the design of purifier for various operational conditions and horizontal shipping. The purifier is designed to withstand 5g force in vertical and 2g force in lateral and longitudinal directions. Transportation experience from vendor to Fermilab and within site is discussed. Integration of the purifier involved design and fabrication of a liquid nitrogen transfer line, regeneration system, and helium piping to connect it to Muon Campus cryogenic system. It also involved establishing electrical, instrumentation and controls connections to the system. Integration of the purifier is discussed in detail. The purifier is to be commissioned using up to 4 MYCOM helium compressors to supply helium and liquid nitrogen supplied by a 60,000-liter tank. Actual effectiveness of the 3-stream heat exchanger is to be estimated based on measured temperatures and flow rate. Impurity levels will be monitored at inlet and outlet of the purifier. Theoretical adsorption capacity of the purifier is calculated based on the measured temperatures and flowrates and is compared to actual adsorption capacity over time.

Subedi, J. [Fermilab] (ORCID:0009000185837576)↗

The interpenetration polymer network in a cement paste–waterborne epoxy system

The formation of the interpenetrating polymer network (IPN) structure within the cement-polymer system has been revealed by experiments from 2 dimensional to 3-dimensional scales. However, the microstructure design and performance prediction of IPN as a function of specific C-S-H/polymer components or ingredients' parameters e.g. water to cement ratios (w/c), polymer to cement ratios (p/c), monomer components, degree of polymerization (DP), etc. is by far not available. Here we developed a mesoscale model for IPN visualization based on the Flory-Huggins interaction theory which was applied to cement science for the first time. All the ingredients in the micro-structure were considered as soluble beads with rational sizes based on their properties obtained by molecular dynamic methods. The interaction parameters of each bead were then determined based on their element ratios and chemical backbones. The model was validated with the waterborne epoxy-cement material (WECM) in which a novel waterborne epoxy resin (WEP) was prepared and impregnated. The verification results on the 2D-3D scale show that the developed model predicts the WECM's IPN structures by rule and line concerning DP, w/c, and p/c in the mixture. The C-S-H beads were progressively scaled in size which alters the C-S-H texture to have completely different dissolution characteristics. Beads of diameter ~6 Å are more unstable and soluble which enable them to form a continuous phase in water or a composite structure with WEP. In contrast, beads with diameters larger than 10 Å have different properties with stronger nucleation effects. The results also suggest the impregnation content of WEP in cement-based material should be limited to 10% vol. to prevent the polymer IPN from decomposing into discrete clusters. The application of Flory-Huggins theory in cement-based composites demonstrates great potential in performance prediction and microstructure design.

36 MATERIALS SCIENCE↗

Value-added catalog of physical properties for more than 1.3 million galaxies from the DESI survey

We present an extensive catalog of the physical properties of more than a million galaxies investigated with the Dark Energy Spectroscopic Instrument (DESI), one of the largest spectroscopic surveys to date. Spanning a full range of target types, including emission-line galaxies, luminous red galaxies, and quasars, our survey encompasses an unprecedented range of spectroscopic redshifts, all the way from 0 to 6. The physical properties, such as stellar masses and star formation rates, were derived via the CIGALE spectral energy distribution (SED) fitting code accounting for the contribution coming from active galactic nuclei (AGNs). Based on the modeling of the optical-mid-infrared (grz supplemented with WISE photometry) SEDs, we studied the galaxy properties with respect to their location on the main sequence. We have revised the dependence of stellar mass estimates on model choices and on the availability of WISE photometry. Indeed, the WISE data are required to minimize the misclassification of star-forming galaxies as AGNs. The lack of WISE bands in SED fits leads to elevated AGN fractions for 68% of star-forming galaxies identified using emission line diagnostic diagrams, but this does not significantly affect their stellar mass or star formation estimates.

79 ASTRONOMY AND ASTROPHYSICS↗

High-Accuracy Mesh-Free Quadrature for Trimmed Parametric Surfaces and Volumes

This work presents a high-accuracy, mesh-free, generalized Stokes theorem-based numerical quadrature scheme for integrating functions over trimmed parametric surfaces and volumes. The algorithm relies on two fundamental steps: (1) We iteratively reduce the dimensionality of integration using the generalized Stokes theorem to line integrals over trimming curves, and (2) we employ numerical antidifferentiation in the generalized Stokes theorem using high-order quadrature rules. Additionally, the scheme achieves exponential convergence up to trimming curve approximation error and has applications to computation of geometric moments, immersogeometric analysis, conservative field transfer between high-order curvilinear meshes, and initialization of multi-material simulations. We compare the quadrature scheme to commonly-used quadrature schemes in the literature and show that our scheme is much more efficient in terms of number of quadrature points used. We provide an open-source implementation of the scheme in MATLAB as part of QuaHOG, a software package for Quadrature of High-Order Geometries.

97 MATHEMATICS AND COMPUTING↗

Practical Guide to Chemometric Analysis of Optical Spectroscopic Data

The methodology and mathematical treatment of several classic multivariate methods for the analysis of spectroscopic data is demonstrated in a straightforward way that can be used as a basis for teaching an undergraduate introductory course on chemometric analysis. The multivariate techniques of classical least squares (CLS), principal component regression (PCR), and partial least squares (PLS), as well as the univariate Beer’s law method have been described and compared, building students’ understanding by starting with the univariate method and progressing step by step into the multivariate methods. Equations for the production of regression vectors from training set spectral data is described and their use demonstrated for the prediction of constituent concentrations on a separate validation set of spectra. Extreme care is taken to ensure consistency in variable formatting of data matrices. This provides a key foundation to understanding how spectral data are manipulated using these different mathematical approaches for building quantitative regression models. Each method is applied to a real-world data set, and the results are discussed to show students the types of information that can be gleaned from each method. A training set comprised of 20 infrared absorbance spectra containing 3 constituents (benzene, polystyrene, and gasoline) of known composition are used to demonstrate the matrix operations for each regression method. A separate set of 12 real-world napalm samples (containing benzene, polystyrene and gasoline) are used as a validation set to demonstrate the ability to utilize the regression models on an unknown dataset. A toolbox (PNNL Chemometric Toolbox) written in MATLAB language is supplied in the Supplemental Information file and can be used as a companion for understanding the development and deployment of the chemometric algorithms described in this paper. The datasets of the infrared spectra are also supplied, allowing users to build and inspect the chemometric models on their own. Finally, the Toolbox includes scripts to assist users in loading their own datasets into MATLAB and performing CLS, PCR, and PLS on their data.

Upper-Division Undergraduate, Analytical Chemistry↗

Features of multilayer mirror application for focusing and collimating X-rays from inverse Compton scattering sources

We have analysed the use of X-ray interference multilayer mirrors as the elements of a focusing scheme for a compact source based on inverse Compton scattering. An algorithm is proposed for selecting mirror parameters, which takes into account the properties of the radiation source. The dependence of wavelength on the viewing angle and the energy line broadening for a fixed viewing angle are found to be the main limitations in the use of multilayer mirrors. Efficient radiation collection calls for the application of broadband mirrors. It is shown that the efficiency of multilayer mirrors in a Kirkpatrick – Baez X-ray focusing setup exceeds that of total external reflection mirrors by an order of magnitude, and that stack multilayer mirrors offer a small advantage over the periodic ones. The overall efficiency of source radiation collection in the photon energy range ΔE = 10 – 12 keV amounts to 12 % for the two-mirror Kirkpatrick – Baez setup. For a spectral region with a bandwidth ΔE/E = 3 %, the efficiency ranges up to 69 %. (paper)

07 ISOTOPE AND RADIATION SOURCES↗

The spectra of IceCube neutrino candidate sources – I. Optical spectroscopy of blazars

ABSTRACT There is mounting evidence that ultra-energetic neutrinos of astrophysical origin may be associated with blazars. Here, we investigate a unique sample of 47 blazars, ∼20 of which could be new neutrino sources. In particular, we focus on 17 objects of yet unknown redshift, for which we present optical spectroscopy secured at the Gran Telescopio Canarias and the ESO Very Large Telescope. We find all sources but one (a quasar) to be BL Lac objects. For nine targets we are able to determine the redshift (0.09 < z < 1.6), while for the others we set a lower limit on it, based on either the robust detection of intervening absorption systems or on an estimation derived from the absence of spectral signatures of the host galaxy. In some spectra, we detect forbidden and semiforbidden emission lines with luminosities in the range 1040–1041 erg s−1. We also report on the spectroscopy of seven blazars possibly associated with energetic neutrinos that partially meet the criteria of our sample and are discussed in the Appendix. These results represent the starting point of our investigation into the real nature of these objects and their likelihood of being neutrino emitters.

Paiano, Simona↗

Why the observed spin evolution of older-than-solar-like stars might not require a dynamo mode change

ABSTRACT The spin evolution of main-sequence stars has long been of interest for basic stellar evolution, stellar ageing, stellar activity, and consequent influence on companion planets. Observations of older-than-solar late-type main-sequence stars have been interpreted to imply that a change from a dipole-dominated magnetic field to one with more prominent higher multipoles might be necessary to account for the data. The spin-down models that lead to this inference are essentially tuned to the Sun. Here, we take a different approach that considers individual stars as fixed points rather than just the Sun. We use a time-dependent theoretical model to solve for the spin evolution of low-mass main-sequence stars that includes a Parker-type wind and a time-evolving magnetic field coupled to the spin. Because the wind is exponentially sensitive to the stellar mass over radius and the coronal base temperature, the use of each observed star as a separate fixed point is more appropriate and, in turn, produces a set of solution curves that produces a solution envelope rather than a simple line. This envelope of solution curves, unlike a single line fit, is consistent with the data and does not unambiguously require a modal transition in the magnetic field to explain it.

Astronomy & Astrophysics↗

Integrated On-Board Charger for Dual Motor Based Electric Vehicle Power Train

This paper presents an integrated on-board charger for dual motor based electric vehicle (EV) power train with silicon carbide semiconductor switch-based traction inverters. The proposed charger architecture reconfigures the traction inverters to be used in the battery charging mode, thereby eliminating several high frequency switches and their accessories. The motor windings are reused as line inductors for the power factor correction (PFC) rectifier stage in the charging mode thereby reducing the requirements of magnetic components. The architectures reduce the cost, weight, and volume of the EV power train. Simulation results are presented to demonstrate the working principle of the proposed architecture.

Mukherjee, Subho [ORNL] (ORCID:0009000672297925)↗

Compatibility of Medium Density Polyethylene (MDPE) for Distribution of Gaseous Hydrogen

Hydrogen has emerged as a convenient energy storage medium and is being considered as an alternative for reducing the use of carbon-based fuels. Numerous projects are looking into distributing blends of natural gas and different amounts of gaseous hydrogen through the existing natural gas distribution system, which is widely composed of medium density polyethylene (MDPE) line pipes. The mechanical behavior of MDPE with hydrogen is not well understood; therefore, the effect of gaseous hydrogen on the mechanical properties of MDPE needs to be examined. In the current study, we investigate the effects of gaseous hydrogen on fatigue crack growth rate, fracture resistance, and fatigue life of MDPE in the presence of 3.4 MPa gaseous hydrogen. Fatigue crack growth behavior and fracture resistance are measured using compact tension specimens, while the fatigue life tests are carried out using circumferential notched tensile specimens. In addition, fatigue and fracture tests were conducted in air to determine the baseline properties of MDPE, which was then compared with the ones observed in gaseous hydrogen environment. After the completion of mechanical testing, fracture surfaces are also analyzed using optical and scanning electron microscopes to understand salient fracture features of MDPE with and without the presence of gaseous hydrogen.

Shrestha, Rakish↗

Final Technical Report

Statement of the problem or situation that is being addressed in your application. The DOE and its national laboratories developed the Home Energy Score™ (HES) to encourage homeowners to improve their energy performance, lower costs and to share energy information through the MLS listing, appraisal, and financing channels. While the HES is an instrumental tool, it is currently underutilized and consists of technical, structural and sector barriers which need to be addressed in order to scale and many energy efficiency contractors are understandably overwhelmed by the added time and effort and lack of incentive to sell and deliver deep retrofit projects while simultaneously meeting the DOE HES program requirements; consequently, contractors may decide to forgo participation. Home Energy Rating System (HERS) Raters have the opportunity to play the critical Assessor role in producing a Home Energy Score (HES); this role has immense potential but currently is unfulfilled. Lastly, while utilities are interested in their customer base achieving greater energy efficiency, especially to help offset growing residential loads in states like California that are accelerating electrification, utilities do not have access to the market actors who are on the front line of influence to homeowners or review and approve their permits: HERS Raters, assessors, contractors and building departments. General statement of how this problem is being addressed: ConSol will integrate the Home Energy Score™ (HES) to its State of California, approved home energy rating services (HERS) platform (CHEERS) to develop a single tool for contractors nationwide to assess, record and install recommended cost, energy, and emissions saving measures to the 140 million single-family homes throughout the U.S. and 14 million homes in California (CHEERS+HES). The CHEERS high fidelity energy code permitting data will be integrated with HES for simple, accurate, easy-to-use home energy estimation and analysis and will directly gain access to the retrofit and renovations markets with the same upgraded platform. This innovative project will assist the utilities in supporting existing homes in their jurisdictions with HES and develop measures to improve energy efficiency and reduce emissions. How is this problem being addressed? What is the overall project approach? In effort to expand the Home Energy Score™ (HES) by increasing the use of aggregable home energy asset data, ConSol proposes to integrate the DOE HES via Application Programming Interface (API) to its State of California approved home energy rating services platform (CHEERS). Once the CHEERS platform and HES are integrated (CHEERS+HES), this enhanced platform will be instantly available and actively deployed via Phase 1 pilot to HERS Raters, assessors and contractors in California to market-test the solution, understand the rate of adoption and identify opportunities for improvement prior to scaling nationally. The CHEERS high fidelity energy code permitting data will be integrated with HES for simple, accurate, easy-to-use home energy estimation and analysis and will directly gain access to the retrofit and renovations markets with the same upgraded platform. This innovative project will assist the building industry and homeowners with an easy-to-use assessment if energy and carbon impacts of existing homes, and assist the utilities in supporting existing homes in their jurisdictions with HES to improve energy efficiency and reduce emissions. What is to be done in Phase I? During Phase I of this proposed project, ConSol will (1) design software architecture that links CHEERS to the Home Energy ScoreTM via API, (2) solicit partnership from one or more California utilities for a regional pilot, (3) test the new software with its HERS Raters and contractor network in the partnership utility jurisdiction, (4) launch a pilot version of the newly developed software with HERS Raters and contractors in the utility territory, and (5) explore California’s GoGreen energy efficiency homeowner lending program in parallel with the pilot. Commercial Applications and Other Benefits. Summarize the future applications or public benefits if the project is carried over into Phase II or Phase III and beyond. The CHEERS+HES commercialized product will be ready for national market scale following a successful Phase 1 performance. The CHEERS+HES adoption is estimated to reach a 5% adoption growth rate versus the 110,000 baseline, starting in Year 1 after Phase I completion, and continuing each year. As a direct benefit to the DOE, CHEERS will set a goal of 100,000 Home Energy Score assessments for existing home alterations within the first 10 years following Phase 1 performance. The technical benefits of this proposed project include the harmonized, automated, and seamless integration of the DOE HES into the widely used and market leading California energy registry, CHEERS. The social benefits include the aggregate energy, cost and GHG savings by allowing the broader public streamlined access to the CHEERS+HES measurement and the energy efficiency recommended measures that may result. Key Words: Home Energy ScoreTM (HES); Application Programming Interface (API); Home Energy Rating Services (HERS); HERS Raters; contractors; assessors; existing homes, energy asset data; cost, energy, and emissions saving measures; energy code (Title 24) compliance; document repository; utilities; pilot; newly developed software; energy efficiency; homeowner. Summary for Members of Congress: The DOE Home Energy Score™ (HES) is a tool to encourage homeowners to improve their energy performance, lower costs and share energy information but is underutilized and consists of barriers which need to be addressed in order to scale. In effort to expand the HES, CHEERS, Inc. will integrate the HES to its State of California, approved home energy rating services (HERS) platform (CHEERS) to develop a single tool for contractors nationwide to assess, record and install recommended cost, energy, and emissions saving measures to the 140 million single-family homes throughout the U.S. and 14 million homes in California.

Application Programming Interface (API)↗

Modeling Needs to Support the Reconstruction Strategy of Ukraine

Ukraine has been facing difficult times. Russia started a full-scale invasion on February 24, 2022, and has caused huge human and infrastructure losses. As a result of the invasion, more than 8 million people left their homes. The Russian army has targeted Ukrainian energy sources, destroying or damaging over 50% of thermal power generation capacity (coal and gas), 30% of solar generation, and 90% of wind generation. The Russians are also threatening Ukrainian energy security, as they currently control the Zaporizhzhia nuclear power plant – Europe’s largest. In addition, Russia has destroyed 121,000 buildings, including 5,300 multistory buildings - more buildings than Ukraine built during the past five years. The occupiers destroyed or damaged 343 district heat boiler stations (destroyed 12 / damaged 331) and 8 CHPs (destroyed 4/ damaged 4). There is no doubt that Ukraine will be able to protect its sovereignty and restore its territorial integrity; however, this will be a long process. The Government of Ukraine needs to simultaneously focus on many issues, from waging war to the restoration of electricity, water, and heat supply in the territories close to the front line. In addition to these time-sensitive issues, the government also needs to plan a long term multi-sector strategy for the reconstruction of Ukraine’s economy. Ukraine initiated a broad-based political process for recovery at the International Ukraine Recovery Conference (URC 2022) in Lugano, Switzerland. Prior to URC 2022, Ukraine applied for EU membership on February 28 and was granted the status of candidate country by the European Council on June 23, 2022. More than 40 nations are fully committed to supporting Ukraine throughout its path from early to long-term recovery. In addition, these countries link a successful recovery to Ukraine’s European future (URC, 2022a). The reconstruction process will be long. The government also recognizes that it is not enough to build energy infrastructure back – it should be built back better. The government is committed to building a more sustainable and cleaner energy sector. Energy modeling can provide important insights into paths to decarbonize Ukraine’s economy while rebuilding it after the war. Pacific Northwest National Laboratory (PNNL) and the Institute for Economics and Forecasting of the National Academy of Sciences of Ukraine (IEF) work on modeling decarbonization scenarios in the energy sector of Ukraine. The teams focus on the heat sector, which includes district heat, autonomous and individual heating, and energy consumption by final energy consumption sectors, including buildings. Since the teams use world-class integrated assessment models, other sectors will be analyzed as well. The purpose of the document is to describe the needs of key Ukrainian ministries in modeling the reconstruction process. The scope of this document is limited to modeling energy consumption by the power and heat sectors, final energy consumption by buildings, and GHG emissions from these two sectors. The rest of this policy memo is organized as follows. After this introduction, Chapter 2 discusses key provisions of the reconstruction strategy with a focus on energy, buildings, heat supply, environment, and European integration aspirations. Section 3 provides an overview of recent developments and key decisions of the Government of Ukraine in the area of energy efficiency and decarbonization. Finally, Section 4 provides key suggestions on how PNNL and IEF can help the Government of Ukraine in developing strategic documents.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Cloud-Based Demonstration of the Eastern Interconnection Situational Awareness Monitoring System (ESAMS)

This report describes a cloud-based implementation and field demonstration of the Eastern Interconnection Situational Awareness and Monitoring System (ESAMS). ESAMS was developed to support the detection and source localization of forced oscillations using synchrophasor measurements from tie-lines connecting areas served by different reliability coordinators (RCs), so that RCs could better coordinate their response to wide-area events. A previous effort had identified deployment barriers associated with hosting shared situational awareness tools at a single RC. To address these barriers, ESAMS was migrated to Amazon Web Services and evaluated in a six-month field demonstration. ISO New England (ISO-NE) and PJM streamed data to the platform using AWS Direct Connect and a site-to-site VPN, respectively. The resulting multi-utility measurement footprint enabled regional source localization across major portions of the U.S. Eastern Interconnection and supported routine identification of oscillation events. During the final three months of the trial, 24 events above 2 MW/MVAR were detected. The largest detected oscillation approached a 25 MW peak-to-peak amplitude, and the longest persisted intermittently for more than 11 hours. The demonstration also assessed operational considerations—including data transfer volumes, end-to-end latency, and cloud computing costs—and found that network and compute requirements were modest relative to typical cloud capabilities while providing performance comparable to prior on-premises deployments. Overall, the results indicate that cloud hosting can provide a practical path to shared interconnection-wide oscillation monitoring. The cloud ESAMS demonstration establishes a foundation for broader utility participation and for building future wide-area analytics that leverage measurements across organizational boundaries.

Follum, James D.↗

Variable Active Galactic Nuclei in the Galaxy Evolution Explorer Time Domain Survey

We searched the northern hemisphere fields of the Galaxy Evolution Explorer Time Domain Survey for galaxies with UV variability indicative of active galactic nuclei (AGNs). We identified 48 high-probability candidate AGNs from a parent sample of 1819 galaxies in the NASA Sloan Atlas catalog. We further characterized these systems using optical spectroscopic diagnostics, Wide-field Infrared Survey Explorer IR color selection criteria, and spectral energy distribution modeling. Of the 48 candidates, eight were identified as AGNs from optical emission lines, two were identified by their IR colors, and 28 were identified through spectral energy decomposition. Observational biases of each selection method are discussed in connecting these AGN subsamples to another. By selecting AGNs based on UV variability, we also identified six low-mass AGN candidates, all of which would have been missed by spectroscopic selection.

79 ASTRONOMY AND ASTROPHYSICS↗

Method and apparatus for mitigating row hammer attacks

An integrated circuit includes an aggressor wordline cache and logic that determines a candidate upper adjacent address and a candidate lower adjacent address of a target memory row corresponding to a read request to memory. When at least one of the candidate upper adjacent address or the candidate lower adjacent address are determined to be a victim row, the logic checks the aggressor wordline cache for a cache hit for the target memory row. When there is a cache hit in the aggressor wordline cache, the logic sends a corresponding cache line as a response to the read request, otherwise the logic causes a read of content from the memory. In certain examples, the logic includes a stored bit array and a hash function-based filter, which determines whether any of the candidate upper adjacent address and the candidate lower adjacent address are victim rows represented in the stored bit array.

SeyedzadehDelcheh, SeyedMohammad↗

Simulation of Peach Bottom turbine trip transient with RETRAN-3D using BXFGEN

The Peach Bottom 2 Turbine Trip transient is used to evaluate the capabilities and accuracy of coupled 3-D neutronics/thermal hydraulics best estimate calculations for support of safety analysis. Selected results, obtained with RETRAN-3D, are compared to available measurements and benchmark results. The comparisons are analyzed and the application of RETRAN-3D for a best estimate analysis approach within the safety analysis methodology is discussed. Overall, both the thermal-hydraulic and neutronic results show a good comparison to the experimental data, and the model is considered to accurately predict test data. In particular, the initial acoustic response of the main steam line and the subsequent main pressurization stages are well-predicted. During the main pressurization stage, the timing and magnitude of the in-core local pressurization and associated void compression are properly predicted based upon the agreement between local power range monitors (LPRM) predictions upwards, but the shift is slightly underpredicted. This indicates the methodology is well-posed for simulating this class of transient response.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

GLIMPSE of Future Power Grid Models

Power grid is one of the critical national infrastructures with social, economics, and national security impacts. Particularly, power distribution systems represent part of the infrastructure between power distribution substations and customers such as residential, commercial, and industrial. To address various grid modernization challenges, state-of-the-art algorithms and methodologies have been developed to deploy, operate, and expand a secure and resilient power grid. At the same time, there is a need to develop capabilities to assist power grid stakeholders to quickly get insight into the design and structure of the grid. Data visualization is a key approach to comprehend and understand complex systems such as the power grid. We present GLIMPSE Grid Layout Interface for Model Preview and System Exploration), a graph-based semantic-aware application to visualize and update distribution power grid models. The GLIMPSE can be used with standard IEEE models to search and highlight power grid objects such as generators, loads, overhead lines, etc. Additionally, it supports updating attributes and model export to integrate with GridLAB-D simulations.

Cybersecurity, power grid, visualization↗

Mining a human transcriptome database for chemical modulators of NRF2

Nuclear factor erythroid-2 related factor 2 (NRF2) encoded by the NFE2L2 gene is a transcription factor critical for protecting cells from chemically-induced oxidative stress. We developed computational procedures to identify chemical modulators of NRF2 in a large database of human microarray data. A gene expression biomarker was built from statistically-filtered gene lists derived from microarray experiments in primary human hepatocytes and cancer cell lines exposed to NRF2-activating chemicals (oltipraz, sulforaphane, CDDOIm) or in which the NRF2 suppressor Keap1 was knocked down by siRNA. Directionally consistent biomarker genes were further filtered for those dependent on NRF2 using a microarray dataset from cells after NFE2L2 siRNA knockdown. The resulting 143-gene biomarker was evaluated as a predictive tool using the correlation-based Running Fisher algorithm. Using 59 gene expression comparisons from chemically-treated cells with known NRF2 activating potential, the biomarker gave a balanced accuracy of 93%. The biomarker was comprised of many well-known NRF2 target genes (AKR1B10, AKR1C1, NQO1, TXNRD1, SRXN1, GCLC, GCLM), 69% of which were found to be bound directly by NRF2 using ChIP-Seq. NRF2 activity was assessed across ~9840 microarray comparisons from ~1460 studies examining the effects of ~2260 chemicals in human cell lines. A total of 260 and 43 chemicals were found to activate or suppress NRF2, respectively, most of which have not been previously reported to modulate NRF2 activity. Using a NRF2-responsive reporter gene in HepG2 cells, we confirmed the activity of a set of chemicals predicted using the biomarker. The biomarker will be useful for future gene expression screening studies of environmentally-relevant chemicals.

59 BASIC BIOLOGICAL SCIENCES↗