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DOE OSTI2014

Carcinogenesis and Inflammatory Effects of Plutonium-Nitrate Retention in an Exposed Nuclear Worker and Beagle Dogs.

The genetic and inflammatory response pathways elicited following plutonium exposure in archival lung tissue of an occupationally exposed human and experimentally exposed beagle dogs were investigated. These pathways include: tissue injury, apoptosis and gene expression modifications related to carcinogenesis and inflammation. In order to determine which pathways are involved, multiple lung samples from a plutonium exposed worker (Case 0269), a human control (Case 0385), and plutonium exposed beagle dogs were examined using histological staining and immunohistochemistry. Examinations were performed to identify target tissues at risk of radiation-induced fibrosis, inflammation, and carcinogenesis. Case 0269 showed interstitial fibrosis in peripheral and subpleural regions of the lung, but no pulmonary tumors. In contrast, the dogs with similar and higher doses showed pulmonary tumors primarily in brochiolo-alveolar, peripheral and subpleural alveolar regions. The TUNEL assay showed slight elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris was present in the inflammatory regions of alveoli and lymph nodes of both the human and the dogs. The expression of apoptosis and a number of chemokine/cytokine genes was slightly but not significantly elevated in protein or gene levels compared to that of the control samples. In the beagles, mucous production was increased in the airway epithelial goblet cells and glands of trachea, and a number of chemokine/cytokine genes showed positive immunoreactivity. This analysis of archival tissue from an accidentally exposed worker and in a large animal model provides valuable information on the effects of long-term retention of plutonium in the respiratory tract and the histological evaluation study may impact mechanistic studies of radiation carcinogenesis.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2022

Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)

Cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs) are increasingly used in cardiac safety assessment, disease modeling and regenerative medicine. A vast majority of cardiotoxicity studies in the past have tested acute effects of compounds and drugs; however, these studies lack information on the morphological or physiological responses that may occur after prolonged exposure to a cardiotoxic compound. In this review, we focus on recent advances in chronic cardiotoxicity assays using hiPSC-CMs. We summarize recently published literature on hiPSC-CMs assays applied to chronic cardiotoxicity induced by anticancer agents, as well as non-cancer classes of drugs, including antibiotics, anti-hepatitis C virus (HCV) and antidiabetic drugs. We then review publications on the implementation of hiPSC-CMs-based assays to investigate the effects of non-pharmaceutical cardiotoxicants, such as environmental chemicals or chronic alcohol consumption. We also highlight studies demonstrating the chronic effects of smoking and implementation of hiPSC-CMs to perform genomic screens and metabolomics-based biomarker assay development. The acceptance and wide implementation of hiPSC-CMs-based assays for chronic cardiotoxicity assessment will require multi-site standardization of assay protocols, chronic cardiac maturity marker reproducibility, time points optimization, minimal cellular variation (commercial vs. lab reprogrammed), stringent and matched controls and close clinical setting resemblance. A comprehensive investigation of long-term repeated exposure-induced effects on both the structure and function of cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2019

Artificial Intelligence

Artificial intelligence is the study of intelligence agents as demonstrated by machines. It is an interdisciplinary field involving computer science as well as, various kinds of engineering and science, for example, robotics, bio-medical engineering, that accentuates automation of human acts and intelligence through machines. AI represents state-of-the-art use of machines to bring about algorithmic computation and understanding of tasks that include learning, problem solving, mapping, perception, and reasoning. Given the data and a description of its properties and relations between objects of interest, AI methods can perform the aforementioned tasks. Widely applied AI capabilities, e.g. learning, are now achievable at large scale through machine learning (ML), large volumes of data and specialized computational machines. ML encompasses learning without any kind of supervision (unsupervised learning) and learning with full supervision (supervised learning). Widely applied supervised learning techniques include deep learning and other machine learning methods that require less data than deep learning e.g. support vector machines, random forests. Unsupervised learning examples include dictionary learning, independent component analysis, and autoencoders. For application tasks with less labeled data, both supervised and unsupervised techniques can be adapted in a semi-supervised manner to produce accurate models and to increase the size of the labeled training data.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2026

PowerAnalytics.jl: User-Centric Power Systems Analysis in Julia

The National Laboratory of the Rockies recently released version 1 of PowerAnalytics.jl, an analysis module for the outputs of its popular open-source electrical power systems modeling platform Sienna. It features an extensible framework - based on the flexible selecting of components, the execution of arbitrary metrics on them, and a familiar DataFrames-based output interface with embedded metadata - to process results in the Sienna style while keeping the interface as simple as possible for non-Julia experts. Here, I describe the package and where it fits into the Sienna ecosystem, how I harnessed user-centered design and Julia features to achieve beginner friendliness without sacrificing performance and expressibility, and what lessons might be drawn from the package's design and implementation.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2024

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence

Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPH ErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-320: The Effect of Survivin Perturbation On the Radiation Response of Breast Cancer Cell Lines

Purpose: Survivin is the smallest member of the inhibitor of apoptosis protein family and is well-known for its universal over-expression in human cancers. Due to its role in apoptosis and cellular proliferation, survivin is implicated in the radiation response in several cancer types, and antisurvivin treatments have had success as a radiation sensitizer in many preclinical cancer models. As no studies to date have reported survivin as a factor affecting radiation resistance in breast cancer models, we sought to evaluate the synergistic relationship between survivin function and irradiation in breast cancer cell lines. Methods: Information regarding survivin protein expression in breast cancer was retrieved from three public databases: Oncomine, Kaplan-Meier Plotter, and GOBO. For the in vitro studies, survivin function was compromised by transducing a non-functional mutant form (survivin-DN) into two breast cancer cell lines, the estrogen receptor-positive MCF7 and the triple-negative, inflammatory SUM149. Cell growth was compared in the survivin-DN and control populations with colony-formation assays. To assess how survivin affects radiation response, clonogenic assays were performed by irradiating the cell lines up to 6 Gy. Results: From the public databases, survivin is more highly expressed in triple-negative breast cancer compared to all other subtypes, and is prognostic of poor survival in all breast cancer patients. In MCF7, the survivin-DN population had decreased colony-formation potential; the opposite was true in SUM149. In the clonogenic assays, abrogation of survivin function radio-protected MCF7 cells in monolayer and 3D growth conditions, while SUM149 survivin-DN cells were radiosensitized in monolayer conditions. Conclusion: We observed synergy between survivin function and radiation, although the results between the two cell lines were disparate. Further investigation is required to identify the mechanism of this discrepancy, including evaluation of the potential role of estrogen receptor status, before proceeding with small-animal experiments.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

HP-FLEX: Field demonstration of the semantics-driven configuration of a Model Predictive Control system to make heat pumps flexible

Model Predictive Control (MPC) has demonstrated significant potential for optimizing building operations and enabling demand flexibility. However, the widespread adoption of MPC is hindered by complex manual configuration and commissioning processes that must be conducted by control experts working alongside building operators. These challenges drive up costs and reduce scalability, particularly when technical human resources and building automation systems are limited, such as in small and medium commercial buildings (SMCBs). This paper demonstrates how semantic standards, specifically ASHRAE 223P, can accelerate the adoption of MPC applications for load flexibility in SMCBs. The authors present a replicable control framework, titled “HP-FLEX” that leverages a building’s semantic model to bootstrap the required data configuration for an MPC controller developed for optimizing heat pump systems as flexible grid resources. The semantic model helps streamline the deployment workflow, particularly for site setup, data/control commissioning, and model setup. This integration enhances portability, transferability, and scalability of the HP-FLEX MPC, which has been developed to support MPC-based supervisory HVAC controllers in SMCBs. Additionally, the paper details the required building and thermostat metadata information to enable the HP-FLEX MPC based on field demonstrations. The new workflow was tested in a small commercial building located in California, U.S., and demonstrated a load shifting performance of 9% based on a dynamic pricing signal that varies by the hour. This work provides a practical pathway for transitioning sophisticated building applications from custom to standardized semantic representations, supporting the broader adoption of advanced control strategies like MPC. The framework also establishes a foundation for evolving metadata requirements as applications mature while maintaining compatibility with industry standards.

Paul, Lazlo↗

DOE OSTI2025

HP-FLEX: Field Demonstration of the Semantics-Driven Configuration of a Model Predictive Control System to Make Heat Pumps Flexible

Paul, Lazlo↗

DOE OSTI2014

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

Purpose: Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. Methods: A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Results: Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were observed in the performance of the two motion models considered. Superior image SNR and contrast were seen using the affine respiratory motion model in combination with the diastole cardiac bin in comparison to the use of the whole cardiac cycle. In contrast, when simultaneously correcting for cardiac beating and respiration, the elastic respiratory motion model outperformed the affine model. In this context, four cardiac bins associated with eight respiratory amplitude bins seemed to be adequate. Conclusions: Considering the compensation of respiratory motion effects only, both affine and elastic based approaches led to an accurate resizing and positioning of the myocardium. The use of the diastolic phase combined with an affine model based respiratory motion correction may therefore be a simple approach leading to significant quality improvements in cardiac PET imaging. However, the best performance was obtained with the combined correction for both cardiac and respiratory movements considering all the dual-gated bins independently through the use of an elastic model based motion compensation.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2014

A Distributed Control System Prototyping Environment to Support Control Room Modernization

Operators of critical processes, such as nuclear power production, must contend with highly complex systems, procedures, and regulations. Developing human-machine interfaces (HMIs) that better support operators is a high priority for ensuring the safe and reliable operation of critical processes. Human factors engineering (HFE) provides a rich and mature set of tools for evaluating the performance of HMIs, however the set of tools for developing and designing HMIs is still in its infancy. Here we propose a rapid prototyping approach for integrating proposed HMIs into their native environments before a design is finalized. This approach allows researchers and developers to test design ideas and eliminate design flaws prior to fully developing the new system. We illustrate this approach with four prototype designs developed using Microsoft’s Windows Presentation Foundation (WPF). One example is integrated into a microworld environment to test the functionality of the design and identify the optimal level of automation for a new system in a nuclear power plant. The other three examples are integrated into a full-scale, glasstop digital simulator of a nuclear power plant. One example demonstrates the capabilities of next generation control concepts; another aims to expand the current state of the art; lastly, an HMI prototype was developed as a test platform for a new control system currently in development at U.S. nuclear power plants. WPF possesses several characteristics that make it well suited to HMI design. It provides a tremendous amount of flexibility, agility, robustness, and extensibility. Distributed control system (DCS) specific environments tend to focus on the safety and reliability requirements for real-world interfaces and consequently have less emphasis on providing functionality to support novel interaction paradigms. Because of WPF’s large user-base, Microsoft can provide an extremely mature tool. Within process control applications,WPF is platform independent and can communicate with popular full-scope process control simulator vendor plant models and DCS platforms.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2015

Detection of microcalcifications by characteristic magnetic susceptibility effects using MR phase image cross-correlation analysis

Purpose: To develop and evaluate a new method for detecting calcium deposits using their characteristic magnetic susceptibility effects on magnetic resonance (MR) images at high fields and demonstrate its potential in practice for detecting breast microcalcifications. Methods: Characteristic dipole signatures of calcium deposits were detected in magnetic resonance phase images by computing the cross-correlation between the acquired data and a library of templates containing simulated phase patterns of spherical deposits. The influence of signal-to-noise ratio and various other MR parameters on the results were assessed using simulations and validated experimentally. The method was tested experimentally for detection of calcium fragments within gel phantoms and calcium-like inhomogeneities within chicken tissue at 7 T with optimized MR acquisition parameters. The method was also evaluated for detection of simulated microcalcifications, modeled from biopsy samples of malignant breast cancer, inserted in silico into breast magnetic resonance imaging (MRIs) of healthy subjects at 7 T. For both assessments of calcium fragments in phantoms and biopsy-based simulated microcalcifications in breast MRIs, receiver operator characteristic curve analyses were performed to determine the cross-correlation index cutoff, for achieving optimal sensitivity and specificity, and the area under the curve (AUC), for measuring the method’s performance. Results: The method detected calcium fragments with sizes of 0.14–0.79 mm, 1 mm calcium-like deposits, and simulated microcalcifications with sizes of 0.4–1.0 mm in images with voxel sizes between (0.2 mm){sup 3} and (0.6 mm){sup 3}. In images acquired at 7 T with voxel sizes of (0.2 mm){sup 3}–(0.4 mm){sup 3}, calcium fragments (size 0.3–0.4 mm) were detected with a sensitivity, specificity, and AUC of 78%–90%, 51%–68%, and 0.77%–0.88%, respectively. In images acquired with a human 7 T scanner, acquisition times below 12 min, and voxel sizes of (0.4 mm){sup 3}–(0.6 mm){sup 3}, simulated microcalcifications with sizes of 0.6–1.0 mm were detected with a sensitivity, specificity, and AUC of 75%–87%, 54%–87%, and 0.76%–0.90%, respectively. However, different microcalcification shapes were indistinguishable. Conclusions: The new method is promising for detecting relatively large microcalcifications (i.e., 0.6–0.9 mm) within the breast at 7 T in reasonable times. Detection of smaller deposits at high field may be possible with higher spatial resolution, but such images require relatively long scan times. Although mammography can detect and distinguish the shape of smaller microcalcifications with superior sensitivity and specificity, this alternative method does not expose tissue to ionizing radiation, is not affected by breast density, and can be combined with other MRI methods (e.g., dynamic contrast-enhanced MRI and diffusion weighted MRI), to potentially improve diagnostic performance.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Considerations of the Differences between Bedded and Domal Salt Pertaining to Disposal of Heat-Generating Nuclear Waste

Salt formations hold promise for eternal removal of nuclear waste from our biosphere. Germany and the United States have ample salt formations for this purpose, ranging from flat-bedded formations to geologically mature dome structures. As both nations revisit nuclear waste disposal options, the choice between bedded, domal, or intermediate pillow formations is once again a contemporary issue. For decades, favorable attributes of salt as a disposal medium have been extoled and evaluated, carefully and thoroughly. Yet, a sense of discovery continues as science and engineering interrogate naturally heterogeneous systems. Salt formations are impermeable to fluids. Excavation-induced fractures heal as seal systems are placed or natural closure progresses toward equilibrium. Engineering required for nuclear waste disposal gains from mining and storage industries, as humans have been mining salt for millennia. This great intellectual warehouse has been honed and distilled, but not perfected, for all nuances of nuclear waste disposal. Nonetheless, nations are able and have already produced suitable license applications for radioactive waste disposal in salt. A remaining conundrum is site location. Salt formations provide isolation and geotechnical barriers reestablish impermeability after waste is placed in the geology. Between excavation and closure, physical, mechanical, thermal, chemical, and hydrological processes ensue. Positive attributes for isolation in salt have many commonalities independent of the geologic setting. In some cases, specific details of the environment will affect the disposal concept and thereby define interaction of features, events and processes, while simultaneously influencing scenario development. Here we identify and discuss high-level differences and similarities of bedded and domal salt formations. Positive geologic and engineering attributes for disposal purposes are more common among salt formations than are significant differences. Developing models, testing material, characterizing processes, and analyzing performance all have overlapping application regardless of the salt formation of interest.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2016

Considerations of the Differences between Bedded and Domal Salt Pertaining to Disposal of Heat-Generating Nuclear Waste

Salt formations hold promise for eternal removal of nuclear waste from our biosphere. Germany and the United States have ample salt formations for this purpose, ranging from flat-bedded formations to geologically mature dome structures. As both nations revisit nuclear waste disposal options, the choice between bedded, domal, or intermediate pillow formations is once again a contemporary issue. For decades, favorable attributes of salt as a disposal medium have been extoled and evaluated, carefully and thoroughly. Yet, a sense of discovery continues as science and engineering interrogate naturally heterogeneous systems. Salt formations are impermeable to fluids. Excavation-induced fractures heal as seal systems are placed or natural closure progresses toward equilibrium. Engineering required for nuclear waste disposal gains from mining and storage industries, as humans have been mining salt for millennia. This great intellectual warehouse has been honed and distilled, but not perfected, for all nuances of nuclear waste disposal. Nonetheless, nations are able and have already produced suitable license applications for radioactive waste disposal in salt. A remaining conundrum is site location. Salt formations provide isolation, and geotechnical barriers reestablish impermeability after waste is placed in the geology. Between excavation and closure, physical, mechanical, thermal, chemical, and hydrological processes ensue. Positive attributes for isolation in salt have many commonalities independent of the geologic setting. In some cases, specific details of the environment will affect the disposal concept and thereby define interaction of features, events and processes, while simultaneously influencing scenario development. Here we identify and discuss high-level differences and similarities of bedded and domal salt formations. Positive geologic and engineering attributes for disposal purposes are more common among salt formations than are significant differences. Developing models, testing material, characterizing processes, and analyzing performance all have overlapping application regardless of the salt formation of interest.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2015

Integrated program for department of energy environmental management office of soil and groundwater remediation - 15426

The subsurface problems that remain at the U.S. Department of Energy (DOE) Office of Environmental Management (EM) sites are technically complex and the costs to complete the cleanup mission are expected to range from $17 billion to $21 billion. There is growing recognition that conventional remedies will not meet regulatory goals at a number of sites and alternative approaches will be required. To address the challenge, the EM Office of Soil and Groundwater Remediation created an integrated program to develop innovative scientific and technical in conjunction with engagement of stakeholders, regulators, and the public. The integrated program provides a holistic approach to assess the risk associated with the remaining challenges facing EM and develop solutions that achieve remediation goals and protect human health and the environment. The integrated program uses a systems-based framework for achieving environmental remediation goals. The framework is based on developing and updating a site conceptual model and includes steps to 1) provide the technical basis for remedial actions, 2) assessments of potential remedies, and 3) implementation and management of remedies to achieve site restoration goals. The Office of Soil and Groundwater remediation defines research and development needed to successfully define and apply the framework. Research opportunities and targets are identified in characterization and conceptual model development, predictions of site conditions, remediation, monitoring, and remediation decision support. Characterization and quantification of key subsurface uncertainties is needed to support conceptual model development, identify contaminant source zones, quantify the flux of contaminants from source terms to points of compliance, and characterize controlling processes for remediation approaches including natural attenuation. Predictive analyses are needed to support development of remediation endpoints, select and design active and in situ or passive remedies, assess remedy performance, and predict long-term contaminant behavior for design of monitoring systems. Advancements are needed to support adaptive remediation approaches and to develop long-term contaminant management strategies for complex sites, such as effective in situ treatment methods for long-lived contaminants ({sup 99}Tc, {sup 129}I, U, Hg, etc.). Monitoring tools and approaches are needed to evaluate remedy performance and plume behavior and decision support methods are needed to quantitatively evaluate remediation alternatives. The Office of Soil and Groundwater Remediation leverages scientific understanding provided through partnerships with the DOE Office of Science, the Department of Defense, and Environmental Protection Agency. These partnerships are helping EM develop scientific understanding and technologies for implementing the assessment framework. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2022

A soil-inspired dynamically responsive chemical system for microbial modulation

Interactions between the microbiota and their colonized environments mediate critical pathways from biogeochemical cycles to homeostasis in human health. Here, in this study, we report a soil-inspired chemical system that consists of nanostructured minerals, starch granules and liquid metals. Fabricated via a bottom-up synthesis, the soil-inspired chemical system can enable chemical redistribution and modulation of microbial communities. We characterize the composite, confirming its structural similarity to the soil, with three-dimensional X-ray fluorescence and ptychographic tomography and electron microscopy imaging. We also demonstrate that post-synthetic modifications formed by laser irradiation led to chemical heterogeneities from the atomic to the macroscopic level. The soil-inspired material possesses chemical, optical and mechanical responsiveness to yield write-erase functions in electrical performance. The composite can also enhance microbial culture/biofilm growth and biofuel production in vitro. Finally, we show that the soil-inspired system enriches gut bacteria diversity, rectifies tetracycline-induced gut microbiome dysbiosis and ameliorates dextran sulfate sodium-induced rodent colitis symptoms within in vivo rodent models.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2017

Sensitivity Analysis of Successful Evacuee Proportion in Hypothetical Seismic Nuclear Emergency Situation

A magnitude 5.8 earthquake, which is the strongest earthquake ever detected in Korea, occurred in Gyeongju on 12 September, 2016. People were worried about not only the impact to their safety and quality of life as directly affected from the earthquake, but also the secondary impact from such a nuclear power plant (NPP) accident incurred by the earthquake. Public awareness is changing such that the risk of earthquakes is no longer a story of other countries. Even if the current situation in Korea is not regarded, it is important to assess the seismic hazard to an NPP and prepare for preventing the effects related with the earthquake impact. Developing a seismic evacuation model is necessary in a part of a level 3 probabilistic safety assessment (PSA) because it is one of the most affecting factors of public radiation exposure and health effects in an emergency phase. In a previous study, a sensitivity analysis of the evacuation speed in a hypothetical NPP accident by an earthquake has been carried out, and population doses resulting from various seismic evacuation scenarios associated with evacuation speed have been compared. In addition to the previous study, the proportion of evacuees who evacuate successfully with adequate speed has been considered and a sensitivity analysis has been performed in this study.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2018

Geomechanical Characterization and Modeling of the Newark Basin

To ensure long-term safety and containment during geologic carbon sequestration operations, understanding reservoir and cap rock behavior under increased pressure conditions is essential. In particular, the risk of induced seismicity has recently emerged as one of the largest concerns for geologic carbon sequestration and other injection operations. Little observational data are available about induced seismicity risks from carbon dioxide injection. However, an increasing number of earthquakes in the continental United States and worldwide are being attributed to human activities that involve other types of underground injection. Analysis of these events suggests that the net injected volume is one of the key factors, and a prolonged injection of large volumes of carbon dioxide is projected to have high potential for triggering similar seismic events. Increased pore pressure may activate an existing critically stressed discontinuity by reducing its frictional resistance to slip, and cause cap rock failure. Even when facture slip does not produce large seismic events felt by humans or cause visible damage, it can increase formation permeability and compromise cap rock integrity, thus increasing the risk of leakage. The Geomechanical Properties of Mesozoic Basins project performed unique research in the Newark Basin by combining detailed laboratory characterization and rock core testing with novel field operations performed on wireline to measure in-situ stress conditions.

58 GEOSCIENCES↗

DOE OSTI2019

Establishment and Characterization of Two Novel Cholangiocarcinoma Cell Lines

Background: Cholangiocarcinoma (CCA) is a rare, aggressive and highly lethal tumor. The disease is very difficult to diagnose and multi-modality treatments are ineffective. To improve our understanding of the biological characteristics of CCA, and facilitate the identification of valid treatments, an in-depth characterization of two novel Chinese patient-derived primary CCA cell lines was performed. Methods: Two CCA cell lines were developed and labelled ZJU-0826 and -1125. The two cell lines were characterized with respect to phenotypic, molecular, biomarker, functional and histological properties. Results: Two novel cell lines were cultured for 2 years, and maintained for more than 100 passages. They retained their typical biliary epithelial morphology and ultrastructure. The population doubling times of ZJU-0826, and -1125 were 63.84 h and 44.73 h, respectively. The cells exhibited near-triploid karyotypes with complex structural aberrations. ZJU-1125 cells had mutations in TP53 exons. Short tandem repeats genotyping confirmed the human origin and difference between lines. An immunophenotype analysis showed that ZJU-0826 is positive for CD44, CD29, Pdx1, CD236, FoxA1, FoxA2, and Nanog, and ZJU-1125 positive for CD44, CD29, CD133, Pdx1, FoxA1, FoxA2, and Nanog. ZJU-1125 had greater invasion ability in vitro and tumorigenicity than those of ZJU-0826. Conclusions: Our results confirm the validity of the ZJU-0826 and -1125 as representative models for the elucidation of the molecular pathogenesis of perihilar CCA, and intrahepatic CCA in both in vitro and in vivo studies, respectively.

62 RADIOLOGY AND NUCLEAR MEDICINE↗