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At least 685 records · Page 38

Conditional reprogrammed human limbal epithelial cells represent a novel in vitro cell model for drug responses

Highlights: • This is the first study describing long term cultures of normal human limbal epithelial cells (CR-LECs) using CR technology. • CR-LEC cells maintain normal karyotype, normal response to DNA damage, well-defined structured spheres in 3D culture. • CR-LEC cells retain the commitment of limbal tissue origin in defined culture conditions. • CR-LEC cells may serve a stable normal human cell model for toxicity assessment. In this study, we established human limbal epithelial cells (LECs) from normal limbal tissues by using Conditional Reprogramming (CR) technology (refer to CR-LEC cells in this study). We have successfully established CR-LEC cell strains from three human donors (3 out of 3), and normal rabbits (2 out of 2) and pig (1 out of 1) as well. CR-LEC cells sustained a continuous and stable proliferation status with a normal karyotype, normal response to DNA damage, well-defined structured spheres in matrigel 3D culture. Responses of CR-LEC cells to IFN α2b, Ganciclovir and 5-Fluorouracil were different, suggesting that these drugs had different toxicities to these cells as expected. More important, there was no significant difference of responses to drugs between early and late passages of CR-LEC cells (p>0.05), indicating CR-LEC cells can serve a stable normal human cell model for toxicity assessment. Toxicity tests with monolayer cultures of CR-LEC cells were measured by staining the F-actin and Dsg-1 expression. Toxicity of three drugs at LD50 concentration resulted in a gradually increased destruction of monolayer, which is, in accordance with the irritation grade of three drugs on human cornea epithelium. Therefore, CR-LEC cells provide a novel and reliable in vitro physiological cell model for corneal toxicity assessment.

60 APPLIED LIFE SCIENCES↗

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.

60 APPLIED LIFE SCIENCES↗

Collaborative Research: Process-resolving Decomposition of the Global Temperature Response to Modes of Low Frequency Variability in a Changing Climate

El Niño-Southern Oscillation (ENSO) and Annular Modes (AMs) represent respectively the most important modes of low frequency variability in the tropical and extratropical circulations. The future projection of the ENSO and AM variability, however, remains highly uncertain with the state-of-the-art coupled general circulation models. A comprehensive understanding of the factors responsible for the inter-model discrepancies in projecting future changes in the ENSO and AM variability, in terms of multiple feedback processes involved, has yet to be achieved. The proposed research aims to identify sources of such uncertainty and establish a set of process-resolving quantitative evaluations of the existing predictions of the future ENSO and AM variability. The proposed process-resolving evaluations are based on a feedback analysis method formulated in Lu and Cai (2009), which is capable of partitioning 3D temperature anomalies/perturbations into components linked to 1) radiation-related thermodynamic processes such as cloud and water vapor feedbacks, 2) local dynamical processes including convection and turbulent/diffusive energy transfer and 3) non-local dynamical processes such as the horizontal energy transport in the oceans and atmosphere. Taking advantage of the high-resolution, multi-model ensemble products from the Coupled Model Intercomparison Project Phase 5 (CMIP5) soon to be available at the Lawrence Livermore National Lab, we will conduct a process-resolving decomposition of the global three-dimensional (3D) temperature (including SST) response to the ENSO and AM variability in the preindustrial, historical and future climate simulated by these models. Specific research tasks include 1) identifying the model-observation discrepancies in the global temperature response to ENSO and AM variability and attributing such discrepancies to specific feedback processes, 2) delineating the influence of anthropogenic radiative forcing on the key feedback processes operating on ENSO and AM variability and quantifying their relative contributions to the changes in the temperature anomalies associated with different phases of ENSO and AMs, and 3) investigating the linkages between model feedback processes that lead to inter-model differences in time-mean temperature projection and model feedback processes that cause inter-model differences in the simulated ENSO and AM temperature response. Through a thorough model-observation and inter-model comparison of the multiple energetic processes associated with ENSO and AM variability, the proposed research serves to identify key uncertainties in model representation of ENSO and AM variability, and investigate how the model uncertainty in predicting time-mean response is related to the uncertainty in predicting response of the low-frequency modes. The proposal is thus a direct response to the first topical area of the solicitation: Interaction of Climate Change and Low Frequency Modes of Natural Climate Variability. It ultimately supports the accomplishment of the BER climate science activity Long Term Measure (LTM): "Deliver improved scientific data and models about the potential response of the Earth's climate and terrestrial biosphere to increased greenhouse gas levels for policy makers to determine safe levels of greenhouse gases in the atmosphere."

58 GEOSCIENCES↗

Theory and experiments join forces to characterize the electrocatalytic interface

Electrocatalysis is gaining impetus as a key technology in fuel cells and for the medium-term energy storage in the context of intermittent, renewable energy sources such as wind and solar power. Furthermore, electrocatalysis promises to convert rather inert molecules such as CO 2 and N 2 into reduced products such as CO and ammonia under relatively mild conditions (1, 2). Harnessing the full power of electrocatalysis is, however, hampered by a lack of understanding of the governing physical and chemical processes at the metal–electrolyte interface. In PNAS, Cheng et al. (3) bring key insight to the characterization of reaction intermediates during CO 2 electroreduction via firstprinciples molecular dynamics modeling. This reaction is timely and has, over the last few years, served as the playground for advanced atomistic modeling of electrocatalysis (4–9).

25 ENERGY STORAGE↗

Development of Two-Step Method for Fast Chloride MSR Neutronics

This work presents neutronics models of a small and large fast-spectrum molten chloride-salt reactor. The models are similar to designs being pursued by industry, and they may serve as generic preconceptual and simplified neutronics models that provide information for decision making in licensing-related areas. Here, the two models were created using Serpent, a Monte Carlo neutron transport code, and Moltres, a neutron diffusion core simulator tool. Specifically, this study focused on exploring the applicability of diffusion theory to fast molten salt reactor (MSR) models, the capabilities of an open-source, MSR-oriented simulation tool (Moltres), and optimal energy-group structures.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Phase-field modeling of solid-state metathesis reactions with the charge neutrality constraint

In this work, we present a phase-field model that captures the evolution of ionic concentrations and phase fractions during solid-state metathesis (SSM) reactions where diffusion limits the rate of transformation. The evolution of the mole fraction of each ion is obtained via governing equations that describe the reduction of a free energy, which includes an energy landscape with local minima located at compositions corresponding to stable products. We utilized two Lagrange multipliers to impose constraints of electroneutrality as well as on the sum of mole fractions, which were then eliminated to derive set of two partial differential equations that describe the dynamics of the mole fraction evolution. From these governing equations, the expressions for effective mobilities for the cations and the anions were obtained. We first study the effect of mobilities of ions on the reaction kinetics, using a simple model considering the ions with an identical absolute value of charge numbers. The simulation results show that the overall characteristic mobility, defined as the sum of the two effective ionic mobilities, provides an excellent measure of the rate at which reaction progresses and that the ratio of the effective mobilities of the anions and the cations signifies the manner by which the reaction progresses. We then generalize the model to consider ions with different charge numbers and tuned the mobility of ions based on their diffusion coefficients reported in the literature and experimental data from a thin-film experiment for the synthesis of FeS 2 to demonstrate the capability of the model to predict the phase evolution during SSM reactions. In particular, the simulation predicts nonplanar phase evolution, which is recently observed in thin-film reactions for the synthesis of FeS 2 via transmission electron microscopy. The approach can serve as a basis for models for phase transformations in other multiphase ionic mixtures, such as in all-solid-state batteries and in ionic liquids.

36 MATERIALS SCIENCE↗

Fire and Thermal Experiments in Support of the Model Evaluation Protocol for LNG Facility Fires

The motivation for the experiments reported here pertains to the siting of Liquefied Natural Gas (LNG) facilities which requires assessing the potential adverse radiant thermal impacts of accidental fires on the public. The objective is to obtain data on jet fires, pool fires, fireballs, and concrete walls that could serve as thermal barriers for model validation. The fuels tested include ethane, ethylene, propane, and isopentane.

42 ENGINEERING↗

Overview of modelling and simulation of metal powder bed fusion process at Lawrence Livermore National Laboratory

The metal laser powder bed fusion additive manufacturing process uses high power lasers to build parts layer upon layer by melting fine metal powders. Qualification of parts produced using this technology is broadly recognised as a significant challenge. Physics based process models have been identified as being foundational to qualification of additively manufactured metal parts. In the present article, a multiscale modelling strategy is described that will serve as the foundation upon which process control and part qualification can be built. This includes a model at the scale of the powder that simulates single track/single multilayer builds and provides powder bed and melt pool thermal data. A second model computationally builds a complete part and predicts manufactured properties (residual stress, dimensional accuracy) in three dimensions. Finally, modelling is tied to experiment through data mining.

36 MATERIALS SCIENCE↗

Improving accuracy of electrochemical capacitance and solvation energetics in first-principles calculations

Here, reliable first-principles calculations of electrochemical processes require accurate prediction of the interfacial capacitance, a challenge for current computationally efficient continuum solvation methodologies. We develop a model for the double layer of a metallic electrode that reproduces the features of the experimental capacitance of Ag(100) in a non-adsorbing, aqueous electrolyte, including a broad hump in the capacitance near the potential of zero charge and a dip in the capacitance under conditions of low ionic strength. Using this model, we identify the necessary characteristics of a solvation model suitable for first-principles electrochemistry of metal surfaces in non-adsorbing, aqueous electrolytes: dielectric and ionic nonlinearity, and a dielectric-only region at the interface. The dielectric nonlinearity, caused by the saturation of dipole rotational response in water, creates the capacitance hump, while ionic nonlinearity, caused by the compactness of the diffuse layer, generates the capacitance dip seen at low ionic strength. We show that none of the previously developed solvation models simultaneously meet all these criteria. We design the nonlinear electrochemical soft-sphere solvation model which both captures the capacitance features observed experimentally and serves as a general-purpose continuum solvation model.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Modeling Heat Loss through Piston and Effects of Thermal Boundary Coatings in Diesel Engine Simulations using Conjugate Heat Transfer models

Heat loss through wall boundaries play a dominant role in the overall performance and efficiency of internal combustion engines. Typical engine simulations use constant temperature wall boundary conditions. These boundary conditions cannot be estimated accurately from experiments due to the complexities involved with engine combustion. As a result they introduce a large uncertainty in engine simulations and serve as a tuning parameter. Modeling the process of heat transfer through the solid walls in an unsteady engine computational fluid dynamics (CFD) simulation can lead to the development of higher fidelity engine calculations. These models can be used to study the impact of heat loss on engine efficiency and explore new design methodologies that can reduce heat losses. In this work, a single cylinder diesel engine is modeled along with the solid piston coupled to the fluid domain. Conjugate heat transfer (CHT) modeling techniques were implemented to model heat losses for a full cycle of a Navistar diesel engine. This CFD model is then validated against experimental data available from thermocouples embedded inside the piston surface. The overall predictions from the model match closely with the experimental observations. The validated model is further used to explore the benefits of thermal barrier coatings (TBC) on piston bowls. The effect of TBC coatings were modeled as a thermal resistance in the heat transfer models. Full cycle 3D engine simulations provide quantitative insights into heat loss and thus calculate the efficiency gain by the use of TBC coatings. The work establishes a validated modeling framework for CHT modeling in reciprocating engine simulations.

Kundu, Prithwish↗

A Geant4 evaluation of the Hornyak button and two candidate detectors for the TREAT hodoscope

The performance of traditional Hornyak buttons and two proposed variants for fast-neutron hodoscope applications was evaluated using Geant4. The Hornyak button is a ZnS(Ag)-based device previously deployed at the Idaho National Laboratory's TRansient REActor Test Facility (better known as TREAT) for monitoring fast neutrons emitted during pulsing of fissile fuel samples. Past use of these devices relied on pulse-shape discrimination to reduce the significant levels of background Cherenkov radiation. Proposed are two simple designs that reduce the overall light guide mass (here, polymethyl methacrylate or PMMA), employ silicon photomultipliers (SiPMs), and can be operated using pulse-height discrimination alone to eliminate background noise to acceptable levels. Geant4 was first used to model a traditional Hornyak button, and for assumed, hodoscope-like conditions, an intrinsic efficiency of 0.35% for mono-directional fission neutrons was predicted. The predicted efficiency is in reasonably good agreement with experimental data from the literature and, hence, served to validate the physics models and approximations employed. Geant4 models were then developed to optimize the materials and geometries of two alternatives to the Hornyak button, one based on a homogeneous mixture of ZnS(Ag) and PMMA, and one based on alternating layers of ZnS(Ag) and PMMA oriented perpendicular to the incident neutron beam. For the same radiation environment, optimized, 5-cm long (along the beam path) devices of the homogeneous and layered designs were predicted to have efficiencies of approximately 1.3% and 3.3%, respectively. For longer devices, i.e., lengths larger than 25 cm, these efficiencies were shown to peak at approximately 2.2% and 5.9%, respectively. Furthermore, both designs were shown to discriminate Cherenkov noise intrinsically by using an appropriate pulse-height discriminator level, i.e., pulse-shape discrimination is not needed for these devices.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Toward Drilling the Perfect Geothermal Well: An International Research Coordination Network for Geothermal Drilling Optimization Supported by Deep Machine Learning and Cloud Based Data Aggregation

The EDGE project, supported by the U.S. Department of Energy Geothermal Technologies Office under award DE-EE0008793, established a data-driven framework for improving the efficiency, cost-effectiveness, and reliability of geothermal well drilling. The project focused on developing scalable data infrastructure, advanced machine learning and probabilistic models, and integrated analytics tools to support continuous drilling optimization. A central objective was to reduce geothermal drilling costs by up to seventy percent while minimizing the risk of well failure through predictive diagnostics and adaptive planning. Over the project period, a comprehensive data repository was designed and deployed, incorporating records from over one hundred geothermal wells across varied geological settings. This repository supported both structured and unstructured data and adhered to FAIR data principles, enabling provenance tracking, quality control, and standardized metadata. The project introduced automated ingestion pipelines and a cloud-hosted platform that facilitated access to raw, processed, and derived datasets. This infrastructure served as the foundation for model development and analysis. Machine learning workflows were developed to predict key drilling metrics including rate of penetration, non-productive time, and total drilling costs. Self-organizing maps and dimensionality reduction methods were used to uncover operational patterns and outliers, while supervised learning algorithms such as random forests and deep neural networks were applied to forecast performance outcomes. The models were validated on heterogeneous datasets from both U.S. and Icelandic fields, demonstrating variable but significant predictive accuracy. The results indicated that finer temporal resolution, inclusion of lithological data, and consistency in operational annotations could substantially improve model performance. The project also implemented process mining techniques to reconstruct state-transition models from drilling event logs. These models enabled the identification of deviations from optimal workflows and provided insights into recurring failure modes. Analysis of non-productive time highlighted the impact of equipment failures, geological challenges, and human factors, offering opportunities for targeted mitigation strategies. The EDGE Dashboard was developed as a web-based expert system integrating data visualization, model outputs, and user-driven queries. It provided an accessible interface for operators to explore historical data, evaluate predicted outcomes, and compare drilling scenarios. Initial feedback from project partners suggested that the dashboard could serve as a foundation for more advanced advisory and optimization tools. Overall, the EDGE project demonstrated the feasibility and value of applying modern data science techniques to geothermal drilling. It delivered a set of interoperable tools and models that can support more efficient, lower-risk well development. The findings point toward a viable path for transitioning from advisory analytics to semi-autonomous drilling systems, contingent on continued collaboration, expanded datasets, and field validation. The project results have immediate relevance for drilling operations, data management practices, and future geothermal R&D efforts aimed at achieving reliable, cost-competitive geothermal energy at scale.

15 GEOTHERMAL ENERGY↗

The spectral evolution of the first Galaxies. III. Simulated James Webb Space Telescope spectra of reionization-epoch galaxies with Lyman continuum leakage

Using four different suites of cosmological simulations, we generate synthetic spectra for galaxies with different Lyman-continuum escape fractions (f (esc)) at redshifts $z\approx 7$–9, in the rest-frame wavelength range relevant for the James Webb Space Telescope (JWST) NIRSpec instrument. By investigating the effects of realistic star formation histories and metallicity distributions on the EW(Hβ)–β diagram (previously proposed as a tool for identifying galaxies with very high f (esc)), we find that neither of these effects are likely to jeopardize the identification of galaxies with extreme Lyman-continuum leakage. Based on our models, we expect that essentially all $z\approx 7\mbox{--}9$ galaxies that exhibit rest-frame $\mathrm{EW}({\rm{H}}\beta )\lesssim 30$ Å to have ${f}_{\mathrm{esc}}\gt 0.5$. Incorrect assumptions concerning the ionizing fluxes of stellar populations or the dust properties of $z\gt 6$ galaxies can in principle bias the selection, but substantial model deficiencies of this type should at the same time be evident from offsets in the observed distribution of $z\gt 6$ galaxies in the EW(Hβ)–β diagram compared to the simulated distribution. Such offsets would thereby allow JWST/NIRSpec measurements of these observables to serve as input for further model refinement.

79 ASTRONOMY AND ASTROPHYSICS↗

KGML-ag: a modeling framework of knowledge-guided machine learning to simulate agroecosystems: a case study of estimating N<sub>2</sub>O emission using data from mesocosm experiments

Abstract. Agricultural nitrous oxide (N2O) emission accounts for a non-trivial fraction of global greenhouse gas (GHG) budget. To date, estimating N2O fluxes from cropland remains a challenging task because the related microbial processes (e.g., nitrification and denitrification) are controlled by complex interactions among climate, soil, plant and human activities. Existing approaches such as process-based (PB) models have well-known limitations due to insufficient representations of the processes or uncertainties of model parameters, and due to leverage recent advances in machine learning (ML) a new method is needed to unlock the “black box” to overcome its limitations such as low interpretability, out-of-sample failure and massive data demand. In this study, we developed a first-of-its-kind knowledge-guided machine learning model for agroecosystems (KGML-ag) by incorporating biogeophysical and chemical domain knowledge from an advanced PB model, ecosys, and tested it by comparing simulating daily N2O fluxes with real observed data from mesocosm experiments. The gated recurrent unit (GRU) was used as the basis to build the model structure. To optimize the model performance, we have investigated a range of ideas, including (1) using initial values of intermediate variables (IMVs) instead of time series as model input to reduce data demand; (2) building hierarchical structures to explicitly estimate IMVs for further N2O prediction; (3) using multi-task learning to balance the simultaneous training on multiple variables; and (4) pre-training with millions of synthetic data generated from ecosys and fine-tuning with mesocosm observations. Six other pure ML models were developed using the same mesocosm data to serve as the benchmark for the KGML-ag model. Results show that KGML-ag did an excellent job in reproducing the mesocosm N2O fluxes (overall r2=0.81, and RMSE=3.6 mgNm-2d-1 from cross validation). Importantly, KGML-ag always outperforms the PB model and ML models in predicting N2O fluxes, especially for complex temporal dynamics and emission peaks. Besides, KGML-ag goes beyond the pure ML models by providing more interpretable predictions as well as pinpointing desired new knowledge and data to further empower the current KGML-ag. We believe the KGML-ag development in this study will stimulate a new body of research on interpretable ML for biogeochemistry and other related geoscience processes.

54 ENVIRONMENTAL SCIENCES↗

A newly proposed isotherm model to predict Cs exchange with crystalline silicotitanate in tank waste simulants

The Zheng Anthony Miller (ZAM) computer model, a multicomponent ion exchange model used to predict the exchange of Group I metals onto crystalline silicotitanate (CST), has historically been used to predict Cs distribution coefficients from Hanford and Savannah River Site (SRS) tank waste simulants. Comparison of experimentally determined Cs distribution coefficients from tank waste simulants with ZAM isotherm model predictions indicate overprediction of Cs and K distribution coefficients for simple and complex simulants with the engineered form of CST. Additionally, recent changes in chemical composition/manufacturing of IONSIV TM R9140-B have resulted in increased Cs capacity from high-salt, highly alkaline solutions. Here, this work served to assess different isotherm models and refine equilibrium parameters to develop a model that can be applied to Hanford and SRS tank waste Cs removal efforts. Toward this goal, the Campbell Westesen Peterson (CWP) model was developed. This model utilized the experimentally determined Cs capacity, and simplified ZAM equilibria expressions to include only the binary substitution of Cs + or K + on the Na + sites. Equilibrium constants for these equations were refined using experimentally determined distribution coefficients. Overall, the CWP model significantly improved our ability to predict both Cs and K loading capacity from complex matrices.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Assessing the Impact of a Forest Canopy on Near-Surface Wind Statistics

Representing the forest canopy in atmospheric numerical models should improve simulated winds within and above the canopy up to a few hundred meters above the ground. Here, in this study, we implement a forest canopy parameterization into the Weather Research and Forecasting (WRF) Model in a large-eddy simulation (LES) mode by applying drag forces across multiple layers within the canopy height. We use unique observations from the Lidar Experiments for Assessing Flow over Forests (LEAFF) field campaign at the Wind River Experimental Forest (WREF) in the U.S. Pacific Northwest to evaluate model performance. In a 2-day case study, the canopy parameterization improved wind predictions both within and above the canopy, particularly during the daytime and at finer grid resolution. Without it, winds were frequently overpredicted above the canopy. Similarly, derived quantities such as the wind shear index also yielded estimates closer to observations with the canopy parameterization implemented. These findings suggest that representing the canopy using drag forces alone can improve simulated mean winds up to 200 m above the surface. Furthermore, second-order statistical moments of wind were more sensitive to canopy density than first-order moments, especially during the daytime. This increased sensitivity and the improved daytime performance in wind speed—evidenced by the lowest bias from observations (3% compared to 20% over diurnal cycle)—imply that winds above the canopy layer are strongly influenced by how well turbulence above the canopy is modeled. The results of this study can serve as a foundation for parameterizing forest canopy effects in coarser weather forecast models.

Energy - Wind↗

REopt Model Overview and Example Use Cases [Slides]

REopt(R) is a mixed-integer optimization model that minimizes the lifecycle cost of serving energy loads at a site. This work provides and introduction to the model along with its key workflow, techno-economic inputs, key outputs, and key caveats for readers to understand REopt the when, why, how of using this model. This resource also includes helpful links related to REopt model and the data sources it uses during the optimization.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Dynamic Line Rating Models and Their Potential for a Cost‐Effective Transition to Carbon‐Neutral Power Systems

Most transmission system operators (TSOs) currently use seasonally steady-state models considering limiting weather conditions that serve as reference to compute the transmission capacity of overhead power lines. The use of dynamic line rating (DLR) models can avoid the construction of new lines, market splitting, false congestions, and the degradation of lines in a cost-effective way. DLR can also be used in the long run in grid extension and new power capacity planning. In the short run, it should be used to help operate power systems with congested lines. The operation of the power systems is planned to have the market trading into account; thus, it computes transactions hours ahead of real-time operation, using power flow forecasts affected by large errors. In the near future, within a “smart grid” environment, in real-time operation conditions, TSOs should be able to rapidly compute the capacity rating of overhead lines using DLR models and the most reliable weather information, forecasts, and line measurements, avoiding the current steady-state approach that, in many circumstances, assumes ampacities above the thermal limits of the lines. Here, this work presents a review of the line rating methodologies in several European countries and the United States. Furthermore, it presents the results of pilot projects and studies considering the application of DLR in overhead power lines, obtaining significant reductions in the congestion of internal networks and cross-border transmission lines.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗