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At least 325 records · Page 18

Chemical and Reactive Transport Processes Associated with Hydraulic Fracturing of Unconventional Oil/Gas Shales

Hydraulic fracturing of unconventional oil/gas shales has changed the energy landscape of the U.S.. Recovery of hydrocarbons from tight, hydraulically fractured shales is a highly inefficient process, with estimated recoveries of < 25% for natural gas and < 5% for oil. This review focuses on the complex chemical interactions of additives in hydraulic fracturing fluid (HFF) with minerals and organic matter in oil/gas shales. These interactions are intended to increase hydrocarbon recovery by increasing porosities and permeabilities of tight shales. However, fluid-shale interactions result in the dissolution of shale minerals and the release and transport of chemical components. They also result in mineral precipitation in the shale matrix, which can reduce permeability, porosity, and hydrocarbon recovery. Competition between mineral dissolution and mineral precipitation processes influences the amounts of oil and gas recovered. We review the temporal/spatial origins and distribution of unconventional oil/gas shales from mudstones and shales, followed by discussion of their global and U.S. distributions and compositional differences from different U.S. sedimentary basins. We discuss the major types of chemical additives in HFF with their intended purposes, including drilling muds. Fracture distribution, porosity, permeability, and the identity and molecular-level speciation of minerals and organic matter in oil/gas shales throughout the hydraulic fracturing process are discussed. Also discussed are analysis methods used in characterizing oil/gas shales before and after hydraulic fracturing, including permeametry and porosimetry measurements, X-ray diffraction/Rietveld refinement, X-ray computed tomography, scanning/transmission electron microscopy, and laboratory- and synchrotron-based imaging/spectroscopic methods. Reactive transport and spatial scaling are discussed in some detail in order to relate fundamental molecular-scale processes to fluid transport. Furthermore, our review concludes with a discussion of potential environmental impacts of hydraulic fracturing and important knowledge gaps that must be bridged to achieve improved mechanistic understanding of fluid transport in oil/gas shales.

04 OIL SHALES AND TAR SANDS↗

Geochemical advances in Arctic Alaska oil typing – North Slope oil correlation and charge history

The Arctic Alaska petroleum province is geologically and geochemically complex. Mixed hydrocarbon charge from multiple source rocks and/or levels of thermal maturity is common within an individual oil pool. Biomarker and chemometric statistical analyses were used to correlate twenty-nine oils to five oil families derived from: (1) Triassic Shublik Formation (calcareous organofacies), (2) Triassic Shublik Formation (shaly organofacies), (3) Jurassic Kingak Shale, (4) Cretaceous shale (pebble shale unit and Hue Shale), and (5) Paleogene shale (Canning Formation). Age-diagnostic and source-related oil biomarker parameters establish clear genetic relationships between the normal oil-window components and their putative source designations. However, application of diamondoid analyses reveals mixed-oil accumulations with postmature charge contributions (diamondoid-rich and biomarker-poor) in many oils. Most sampled reservoirs contain a predominant charge derived from a single oil-window source plus a minor contribution from one or more higher maturity source(s). Variations in source organofacies also are recognized in the Shublik, Kingak, and Cretaceous oil families. In some cases, oils from multiple pools within a single field display relatively homogeneous geochemical profiles, suggesting a common source and migration pathway. For example, oil from the significant Pikka discovery is inferred to originate mainly from the calcareous Shublik Formation. In other cases, variability among oils from multiple pools within a single field (e.g., Milne Point, Colville River, and Northstar) likely indicates a more complex source, migration, and charge history. The results of this study may be useful for anticipating the composition of oil charge in stratigraphic traps with low-permeability sandstone reservoirs, where oil gravity and other chemical parameters may influence economic viability.

58 GEOSCIENCES↗

Modeling nuclear waste disposal in crystalline rocks at the Forsmark and Olkiluoto repository sites – Evaluation of potential thermal–mechanical damage to repository excavations

We conduct coupled thermo-hydro-mechanical modeling of a KBS-3V repository design in crystalline rocks, using data and conditions from the Forsmark in Olkiluoto repository sites in Sweden and Finland. The study focuses on repository performance related to the impact of thermal and hydraulic evolution on the potential for thermal–mechanical damage to underground repository excavations. For the designs and conditions considered at the Forsmark and Olkiluoto repository sites, the simulations show a peak temperature well under the adopted performance target of a 100°C maximum temperature, whereas there is still a high potential for thermal–mechanical damage to the KBS-3V waste deposition holes. The thermal–mechanical damage is much more likely if rock permeability is so low that it delays saturation and swelling of bentonite-clay-based backfill beyond the time for the thermal–mechanical peak, which occurs 50 to 100 years after nuclear waste deposition. We also found that sidewalls of the KBS-3V emplacement tunnels are vulnerable to tensile fracturing due to the combined effect of thermal stressing and backfill swelling. The study highlights a strong interaction between bentonite-based backfill and host rock through capillary suction along with induced rock desaturation. A careful design and selection of the bentonite-clay-based backfill materials for KBS-3V tunnels and deposition holes can facilitate a timely saturation and backfill swelling that in turn can minimize thermal–mechanical damage.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Spatial Mapping of Riverbed Grain-Size Distribution Using Machine Learning

Recent alluvial sediments in riverbeds play a significant role in controlling hydrologic exchange flows (HEFs) in river systems. The alluvial layer is usually associated with strong heterogeneity in physical properties (e.g., permeability and hydraulic conductivity), which affects local HEFs and therefore biogeochemical processes. The spatial distribution of these physical properties needs to be determined to inform the numerical models used to reveal the realistic hydro-biogeochemical behaviors. Such information can be obtained based on the intrinsic link between sediment grain-size distribution and hydraulic properties where sediment texture information is available. However, grain-size measurements are usually spatially sparse and do not have adequate coverage and resolution, particularly for a relatively large domain such as the Hanford Reach of the Columbia River. In this paper, we adopted machine learning (ML) approaches for categorizing and mapping the spatial distributions of riverbed substrate grain size and filling in missing areas of substrate data using the ML models along the reach. Such ML models for substrate size mapping were trained at 13,372 locations using measured substrate sizes along with observed and simulated attributes, including bathymetric attributes (e.g., elevation, slope, and aspect ratio) from LIDAR and bathymetric surveys, and hydrodynamic properties (e.g., water depth, velocity, shear stress, and their statistical moments). An ensemble bagging-based ML technique, Random Forest, was adopted to identify the most influential factors as predictors to develop the predictive models with over-fitting issues addressed. The models were evaluated with respect to each individual substrate size class and the lumped group, and then used to generate the final substrate size maps covering all the grid cells in the numerical modeling domain.

54 ENVIRONMENTAL SCIENCES↗

A General Model for the Ductility of Intermetallics Applied to Fe-Co Alloys

The mechanical properties, specifically ductility, of high performing soft magnets such as Fe-Co alloys are a limiting factor to their broader use in a number of systems. The understanding of the mechanical robustness in these materials is currently insufficient to be able to support the growing interest in applications such as magnetic shielding or electric motors. Fe-Co alloys provide the highest commercially available magnetic saturation and high magnetic permeability but have very poor ductility. The addition of vanadium to these alloys has allowed for significant commercialization and some ductility improvements, but the fundamental reasons for the observed improvements are not well understood. In most published work on mechanical properties in these alloys, the precise chemistry of the alloys investigated, often a critical aspect of intermetallics, is not reported or controlled and thermal history is unclear. This work creates a ductility model that is sensitive to changes in chemistry and can predict relative strain to failure as well as brittle fracture mode for intermetallics and is applied to Fe-Co alloys. Through the application of density functional theory (DFT), this model identifies defect stabilities, anti-phase boundary (APB) energies, the energy necessary to cross-slip, and cleavage energies and combines them through energetic competition to determine a relative failure strain. The model correctly predicts ductility improvements with the addition of vanadium as well as the transition from intergranular to transgranular cleavage, though more precise experiments are necessary to appropriately validate the various improvements observed.

36 MATERIALS SCIENCE↗

Well-Controlled Hydro-thermo-chemical Stimulation of a Coso Geothermal Well to Enhance Productivity

The goal of this project was to demonstrate controlled fracturing and permeability increase to enhance resource production and power generation at Coso. It was planned to stimulate at least two intervals in the Well 73-18RD with zonal isolation using advanced high-temperature packer technology. The anticipation was that a hydraulic fracture would form in one zone and in the second zone natural fractures would reopen, shear and extend, thereby increasing fluid communication in the field. In both cases, the intent was to carefully design the stimulation to take advantage of the relative roles of hydraulic pressure, thermal stress and chemical (“hydro-thermo-chemical”) dissolution. The project had planned to use the Welltec Annular Barrier (WAB) system developed as part of another DOE-funded project which was on schedule to be ready for field deployment. If successful, the Coso Operating Company would incorporate this approach into their ongoing well maintenance in other wells increasing the total MWs produced. The project had multiple tasks and the objective of Task 1 was to develop a workover plan, to build a geologic model, to design a stimulation program, and to work with the operating and services companies to develop a detailed budget and obtain the necessary permits and sundry notices. In Phase 2 the workover plan would be implemented, the designed stimulation would be carried out, and subsequently the well would logged and tested to measure the impact of stimulation. Per sponsor request, a Pre-Task 1 activity with a Go/No Go decision point was scheduled in Task 1.

02 PETROLEUM↗

Proton Conducting Silicon Oxide Membranes as a Fluorine Free Alternative to Nafion for Low Temperature Water Electrolysis

Driven by environmental and health concerns related to per- and polyfluoroalkyl substances (PFAS), there has been growing interest in developing fluorine-free proton (H + ) exchange membrane (PEM) materials for fuel cells and water electrolyzers. In this study, we present a side-by-side comparison of the key transport properties of submicron thick, PFAS-free amorphous silicon dioxide (SiO 2 ) membranes to Nafion, a fluorinated polymer electrolyte membrane that represents the industry standard for PEM fuel cells and electrolyzers. Here, measurements of proton (H + ) conductivity (σ H + ), hydrogen (H 2 ) permeability (P H 2 ), and electrical resistivity (ρ e – ) were conducted using model thin films comprised of SiO 2 membranes deposited by atomic layer deposition (ALD). Although the H + conductivity of the SiO 2 membranes is 2–3 orders of magnitude lower than Nafion, the addition of phosphorus dopants (PO x ) improves H + conductivity such that the area specific membrane resistance of thin (<50 nm) PO x -doped SiO 2 membranes is more than an order of magnitude lower than Nafion-117. Importantly, the safe operation of such nanoscale membranes within a PEM electrolyzer is feasible thanks to the low H 2 permeability of dense SiO 2 -based membranes, which are predicted to limit H 2 crossover rates to acceptable levels for pressures up to ≈ 100 bar. As a proof-of-principle demonstration, a chip-scale water electrolyzer based on 100 nm thick PO x -SiO 2 membrane is shown to achieve a current density of 2 A cm –2 at a potential of 2.5 V. If this technology can be successfully scaled up, H + conducting oxide membranes offer an attractive PFAS-free alternative to Nafion for efficient and durable water electrolysis and fuel cell technologies.

Nafion↗

Utah FORGE Core Material Friction Experiments

The following folders contain 3 friction experiments on Utah FORGE core material from depths of 6735 - 8533ft. The experiment conditions range from 100% relative humidity at room temperature to fluid-saturated at 110C. Experiments were done on both intact samples in a single-direct shear configuration, double-direct shear, and gouge.

15 GEOTHERMAL ENERGY↗

Probing the Damage Zone at Parkfield

Rocks are heterogeneous materials that exhibit nonlinear elastic (anelastic) behavior at scales ranging from the laboratory to Earth. In the laboratory, typical, complex relationships exist between stress and strain that include hysteresis, finite relaxation times, strain rate, and history dependence. These behaviors are linked to important characteristics such as stress, porosity, permeability, material integrity, and material failure. In this work, we adopted a “pump-probe” type experiment common in laboratory studies, using solid earth tides as the low-frequency pump and empirical Green's function as the high-frequency probe. By probing the velocity at different points in the pump cycle, we constrained important information about the strain-modulus relationship. Near the San Andreas Fault, we observed strongly nonlinear elastic behavior that characterizes the damage zone. We also constrained important aspects of hysteretic behavior that are related to damage properties and possibly pore pressure. Away from the fault, the nonlinear behavior is diminished.

58 GEOSCIENCES↗

New insights into the drainage of inundated ice-wedge polygons using fundamental hydrologic principles

Abstract. The pathways and timing of drainage from the inundated centers of ice-wedge polygons in a warming climate have important implications for carbon flushing, advective heat transport, and transitions from methane to carbon dioxide dominated emissions. Here, we expand on previous research using a recently developed analytical model of drainage from a low-centered polygon. Specifically, we perform (1) a calibration to field data identifying necessary model refinements and (2) a rigorous model sensitivity analysis that expands on previously published indications of polygon drainage characteristics. This research provides intuition on inundated polygon drainage by presenting the first in-depth analysis of drainage within a polygon based on hydrogeological first principles. We verify a recently developed analytical solution of polygon drainage through a calibration to a season of field measurements. Due to the parsimony of the model, providing the potential that it could fail, we identify the minimum necessary refinements that allow the model to match water levels measured in a low-centered polygon. We find that (1) the measured precipitation must be increased by a factor of around 2.2, and (2) the vertical soil hydraulic conductivity must decrease with increasing thaw depth. Model refinement (1) accounts for runoff from rims into the ice-wedge polygon pond during precipitation events and possible rain gauge undercatch, while refinement (2) accounts for the decreasing permeability of deeper soil layers. The calibration to field measurements supports the validity of the model, indicating that it is able to represent ice-wedge polygon drainage dynamics. We then use the analytical solution in non-dimensional form to provide a baseline for the effects of polygon aspect ratios (radius to thaw depth) and coefficient of hydraulic conductivity anisotropy (horizontal to vertical hydraulic conductivity) on drainage pathways and temporal depletion of ponded water from inundated ice-wedge polygon centers. By varying the polygon aspect ratio, we evaluate the relative effect of polygon size (width), inter-annual increases in active-layer thickness, and seasonal increases in thaw depth on drainage. The results of our sensitivity analysis rigorously confirm a previous analysis indicating that most drainage through the active layer occurs along an annular region of the polygon center near the rims. This has important implications for transport of nutrients (such as dissolved organic carbon) and advection of heat towards ice-wedge tops. We also provide a comprehensive investigation of the effect of polygon aspect ratio and anisotropy on drainage timing and patterns, expanding on previously published research. Our results indicate that polygons with large aspect ratios and high anisotropy will have the most distributed drainage, while polygons with large aspect ratios and low anisotropy will have their drainage most focused near their periphery and will drain most slowly. Polygons with small aspect ratios and high anisotropy will drain most quickly. These results, based on parametric investigation of idealized scenarios, provide a baseline for further research considering the geometric and hydraulic complexities of ice-wedge polygons.

Harp, Dylan R. (ORCID:0000000197778000)↗

Iron-modified biochar-based bilayer permeable reactive barrier for Cr(VI) removal

In this study, iron (Fe)-modified biochar (FeBC) has been developed to remove hexavalent chromium (Cr(VI)) from groundwater and is suitable for use in permeable reactive barriers (PRBs). However, Cr(VI) removal behavior and chemical processes in FeBC-based PRBs are not fully understood, and the potential for Fe release has not been addressed. In this study, three FeBC-based PRBs were assessed in column experiments for 563 days with respect to their ability to remove Cr(VI). Bilayer column filled with FeBC+limestone and BC+limestone in two separate layers (FeBC_Ca_BC) showed the best performance in terms of Cr(VI) removal with a low treatment cost. The corrosion of FeBC was mainly related to pH and Cr(VI) concentration rather than flow rate. Leached Fe was attenuated by BC and limestone and reutilized in FeBC_Ca_BC. Cr(VI) was reduced to Cr(III) and then adsorbed or precipitated on the biochars. Cr and Fe formed inner-sphere complexes and then transformed from double corner sharing to edge sharing. During the reaction, Cr penetrated from the surface to the interior of the biochars and became a more stable species. This study provides evidence of the effectiveness of a new combination of biochars for Cr(VI) removal and insights into the reaction mechanisms.

42 ENGINEERING↗

Spontaneous sodium ion storage behaviors of reduced graphene oxide anodes exceeding 100% Coulombic efficiency by modulated ion solvation

Rechargeable batteries are essential energy storage devices that power portable devices and electrical vehicles throughout the world. In general, it is thought that the electrochemical performance of rechargeable batteries is mostly determined by the electrodes within them and that the electrolyte plays a relatively passive role. However, ion transport and storage can be greatly influenced by the electrolyte solution structure, specifically, ion solvation within the bulk and ion desolvation across the electrode/electrolyte interfaces. Herein, we studied the role of the electrolyte as an active component of electrochemical energy storage devices. We found that with an appropriate electrolyte formulation, ion storage in disordered carbonaceous anode materials can occur spontaneously without externally supplied electrical energy. Reduced graphene oxide (RGO) in an ether-based electrolyte demonstrates ‘spontaneous' ion storage behaviors of adsorbing and inserting the solvated ions utilizing facilitated permeability and wettability of RGO, which results in Coulombic efficiency of ~145% due to additional charging capacity of ~180 mAh g -1 during electrochemical processes. The unexpected spontaneous ion storage behavior was extensively investigated using a combination of electrochemical analyses and diagnostics, advanced characterizations, and computational simulation. In conclusion, we believe the spontaneous ion storage behavior offers a new way to further improve the energy efficiency of practical rechargeable batteries.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Production of β-ketoadipic acid from glucose in Pseudomonas putida KT2440 for use in performance-advantaged nylons

Biomass-derived chemicals can offer unique chemical functionality relative to petroleum-derived building blocks. To this end, here we report that β-ketoadipic acid (βKA), a C6 diacid with a β-ketone group, can be used as a performance-advantaged replacement for adipic acid in a nylon-6,6 analog. Building on our previous efforts to produce shikimate-derived products from carbohydrates, Pseudomonas putida KT2440 is engineered to produce βKA from glucose, achieving a 26 g/L titer. Following purification, βKA imparts an increase of 69 degrees C above the nylon-6,6 glass transition temperature and 20% reduced water permeability, equivalent to nylon-6,10. Molecular simulations predict that the enhanced thermal properties result from rigidity introduced by the β-ketone. Process analysis predicts that βKA can be produced for US$1.94/kg from sugars, requiring 63% less energy and emitting 43% less greenhouse gases than fossil-based adipic acid. Overall, this study illustrates the potential for βKA to serve as a useful building block for bio-based polymers.

09 BIOMASS FUELS↗

Porous Organic Cage Membranes for Molecular Gas Separations (Final Technical Report for DE-SC0021357)

This proposal aims at demonstrating the development of a novel family of membranes, composed of porous organic cages (POC) which offer the possibility of displaying high separation performance for challenging molecular gas separations relevant to natural gas purification, and olefin/paraffin separation. The proposed POCs synthesized in membrane form will display the most desirable properties of polymers (facile processability and flexibility) and inorganic materials (hierarchically ordered pores with molecular sieving properties) leading to highly selective and permeable membranes. POCs should display distinctive structural, compositional, adsorption and transport properties than those of conventional porous materials, opening the doors for a new research direction in membrane science, and gas separations. Our preliminary results demonstrate the feasibility of preparing POC crystals with controlled size, and continuous POC membranes with remarkable high permeances, and separation ability for CO 2 /CH 4 , N 2 /CH 4 and C 3 H 6 /C 3 H 8 separations serving as a solid foundation for our proposed work. Fundamentally, this proposal aims at elucidating separation mechanisms of different gas mixtures related to natural gas composition, and olefin/paraffin separation over porous organic cage membranes. The proposed research will result in fundamental understanding of adsorption and transport properties of industrially relevant gas molecules through novel microporous membranes, and may lead to the development of a cost effective membrane technology for natural gas purification, and olefin/paraffin separation surpassing the conventional benchmark technology distillation. Furthermore, we aim at demonstrating selective water transport through POC membranes, which can be positively impactful in numerous industrial applications in which water is present. The ability to fabricate thin, chemically and mechanically stable POC membranes for societal relevant gas separations constitute a new and distinctive direction in membrane science. Our proposed work aims at addressing some of the challenges recognized in the Research Agenda for Transforming Separation Science . Specifically: (a) advancing understanding of complex mixtures on separation performance; (b) exploring thermodynamic and kinetic mechanisms through the elucidation of separation mechanisms, and (c) study potential stability issues of the membranes to be assessed by evaluating the long term membrane stability and performance at various temperatures and pressures. The team is uniquely qualified to execute the proposed work. The PI has solid expertise in the rational molecular engineering design of porous crystalline membranes for molecular gas separations. The PNNL collaborator has extensive experience in the synthesis, characterization, and functional applications of microporous crystals, with particular emphasis on gas adsorption.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Investigation of Scale-Dependent Groundwater/Surface-water Exchange in Rivers by Gradient Self-Potential Logging: Numerical Modeling and Field Experiments

Exchanges of groundwater and surface-water are fundamental to a wide range of water-supply and water-quality management issues but challenging to map beyond the reach scale. Waterborne gradient self-potential (SP) measurements are directly sensitive to water flow through riverbed sediments and can be used to infer exchange locations, direction (gain versus loss), scale, and relative changes, but to date applications to river corridor hydrology are limited. Numerical modeling and field experiments were therefore performed herein, each emphasizing waterborne gradient SP logging for identifying and locating focused vertical groundwater discharge (surface-water gain) and recharge (surface-water loss) in a river. Two and three-dimensional numerical models were constructed to simulate the polarities, appearances, and peak amplitudes of streaming-potential and electric-field anomalies on a riverbed and in the surface-water that were attributable to steady-state vertical fluxes of groundwater through high-permeability conduits in the riverbed. Effects of varied hydraulic length-scale of exchange and surface-water depth were tested through numerical modeling. Modeling results aided in data acquisition and interpretation for three repeated field experiments performed along a 1.5–2.0 km reach of the Quashnet River in Cape Cod, Massachusetts, where focused, meter-scale groundwater discharges occur at discrete locations within otherwise ubiquitous and more diffuse groundwater upwelling conditions. Strong gradient SP anomalies were repeatedly measured in the Quashnet River at previously confirmed locations of focused groundwater discharge, showing the efficacy of waterborne gradient SP logging in identifying and characterizing groundwater/surface water exchange dynamics at multiple river network scales.

Engineering↗

Tritium Transport Phenomena in Molten-Salt Reactors

In this work, we review phenomena relevant to tritium transport in molten-salt reactors, which produce tritium from lithium and beryllium salts at significantly higher levels than other reactor types. Modeling of such phenomena began following MSRE operations, and these early models attempted to predict measured tritium distributions in the MSRE, accounting for turbulent mass-transport processes (using established heat transfer correlations), permeation through a variety of metal structures such as heat exchanger tubes, and transport to and from bubbles introduced into the salt by gas sparging. The models reasonably reproduced the MSRE data, but did so best when the permeability of structures was reduced by about a factor of 1,000. This issue does not appear to have been conclusively resolved, and all of the more recent attempts to model tritium transport in molten salts appear to make use of the same methodology. MSRE remains, however, essentially our only source of integral tritium transport data relevant to MSRs. Here, we generalize the MSRE approach to permeation in order to include potential rate-limiting effects at interfaces, as well the effects of added hydrogen. Appropriately non-dimensionalized, this system of equations identifies two dimensionless numbers whose relative values clearly delineate the conditions under which mass transport, surface effects, permeation, and hydrogen swamping are expected to become rate-limiting. We also describe the preliminary conceptual design of a forced convection FLiBe loop, into which tritium would be introduced for the purpose of providing validation data for such a model. The primary purpose of this is to investigate the coupled transport phenomena described above and identify those that are rate-limiting in MSRs. Additional test section configurations are described that would address other transport phenomena relevant to MSRs, including bubbly flows and graphite interactions.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

LLNL 5-2428: Fracture Permeability and Seismic Slip Behavior

Our goal is to develop, apply and validate a holistic thermal, hydrologic, mechanical, and chemical (THMC) workflow that also includes evaluation of induced seismic slip in EGS reservoirs. We will integrate experimental and modelling approaches to reduce parameteruncertainty and better predict and mitigate seismic hazard at Utah FORGE and future EGS sites.We propose a novel approach that incorporates 3D physics-based Earthquake simulations in THMC models, herein referred to as “THMC+E” models. This capability will enable improvedengineering decisions at Utah FORGE and move EGS operations toward repeatable, robust, economically viable, and socially accepted development. Utah FORGE management and future EGS operators may employ results of THMC+E models for decision making purposes throughout the lifetime of the field operation. For example, before production well installation, our THMC+E models will predict circulation scenarios and related seismic hazard for a suite ofpossible well locations and flow rates, thus enabling evaluation of optimal production well placement. Such efforts will be conducted throughout the lifetime of the project, whereby additional laboratory experiments will constrain key model parameters and machine learning (ML) will reduce the size of the parameter space and the associated uncertainty. THMC+E simulations will enable exploration various circumstances that may hinder EGS success and develop mitigation strategies.

58 GEOSCIENCES↗

Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor

Highlights: • Lenvatinib combined with radiation significantly inhibits thyroid cancer growth. • Combined therapy induced apoptosis and G2/M phase cell cycle arrest. • Irradiation increased cellular uptake of lenvatinib into cancer cells. • Combined therapy suggests a new therapeutic strategy for advanced thyroid cancer. Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5–15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗