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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Breast cancer stem cells, EMT and therapeutic targets

Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels

Cancer cell migration and invasion involves actin cytoskeleton reorganization, which is regulated by the WASP (Wiskott Aldrich Syndrome Protein) family of proteins such as WASP, N-WASP (Neural-WASP) and WASP interacting protein (WIP). In this study, we found that the expression of WIP was significantly upregulated in metastatic A5-RT3 cells compared to its parental non-tumorigenic HaCaT cells. Using A549 human lung adenocarcinoma cell line as the model system, we found that WIP regulates cell invasion, proliferation and anchorage-independent growth. Expression of WIP was enhanced during TGF-β1 induced epithelial-mesenchymal transition (EMT) and overexpression of WIP accelerated EMT while knocking down WIP attenuated EMT associated morphological changes. Knocking down WIP expression in A549 cells significantly reduced RhoA levels and WIP was found to interact with RhoA suggesting that WIP might be executing its function by regulating RhoA. Acquisition of invasive, proliferative properties and anoikis resistance is the central step in metastasis indicating a novel function of WIP in cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

High ALDH activity defines ovarian cancer stem-like cells with enhanced invasiveness and EMT progress which are responsible for tumor invasion

Highlights: • Pluripotent, invasive and EMT-related genes are positively correlated. • The definition of ovarian ALDH{sup high} CSCLs is verified by their higher colony-formation, multipotent-genes expression and tumorigenicity. • Ovarian ALDH{sup high} CSCLs display advanced invasiveness, EMT progress and apoptosis-resistance. • ALDH{sup high} CSCLs take chief charge of EOC invasion, due to their elevated stemness and metastatic features. Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare population of undifferentiated oncogenic cells responsible for tumor initiation and maintenance. We identified ovarian cancer ALDH{sup high} (aldehyde dehydrogenase) population could perform not only strengthened CSCLs properties embodied in colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a greater invasive capacity with advanced EMT progress and anti-apoptosis compared with ALDH{sup low} cells. Furthermore, both the stemness and aggressive features, along with ALDH{sup high} percentages were in positive association with the invasiveness of cell lines for sorting, indicating the promotive role of ALDH{sup high} CSCLs in EOC neoplasia and metastasis, since the whole tumor was derived from the CSCLs with hyperactive self-renewal and aggression. Collectively, this study illustrates the interplay between ALDH{sup high} CSCLs and EOC invasion, and offers a novel application target for the EOC oncotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CXCL5 promotes mitomycin C resistance in non-muscle invasive bladder cancer by activating EMT and NF-κB pathway

Highlights: • A mitomycin C-resistant bladder cancer cell line named M-RT4 is established. • The level of CXCL5 in M-RT4 is much higher than that in parental RT4 cell. • Treated with CXCL5 reduces the sensitivity to mitomycin C of RT4 cell, while knockdown CXCL5 sensitizes M-RT4 cell. • EMT and NF-κB pathway play important roles in CXCL5-mediated chemoresistance. The emergence of chemoresistance greatly increases the recurrence risk for non-muscle invasive bladder cancer (NMIBC) patients, which is still a big concern of clinicians. Understanding the mechanisms of drug resistance is of great significance for preventing and reversing it. We showed here that CXC motif chemokine ligand 5 (CXCL5) was overexpressed in mitomycin C-resistant bladder cancer cell line M-RT4. Meanwhile, parental RT4 cell treated with recombinant human CXCL5 (rhCXCL5) reduced its sensitivity to mitomycin C. Conversely, knockdown CXCL5 sensitized M-RT4 cell. We further investigated the molecular mechanisms finding that epithelial mesenchymal transition (EMT) and NF-κB pathway were activated in M-RT4 cell, which could be attenuated by knockdown CXCL5. All these data indicated that CXCL5 may promote mitomycin resistance by activating EMT and NF-κB pathway. Thus, our study identifies CXCL5 as a novel chemoresistance-related marker in NMIBC, thereby providing new strategies to overcome chemoresistance for NMIBC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MiR-616-3p promotes angiogenesis and EMT in gastric cancer via the PTEN/AKT/mTOR pathway

Highlights: • 1, miR-616-3p was up-regulated in GC cell lines and tissues, indicating a poor prognosis. • 2, miR-616-3p promoted angiogenesis and EMT in vitro. • 3, miR-616-3p exerted its biological function might through AKT/mTOR pathway by targeting PTEN. • 4, miR-616-3p might be a potential therapeutic target in GC. Dysregulation of microRNAs has been demonstrated to be involved in a variety of biological events related to cancer, including proliferation, metastasis, angiogenesis and immune escape. MiR-616-3p is located on the chromosome region 12q13.3, however, its potential role and clinical implications in gastric cancer remain poorly understood. The current study aimed to investigate the potential role of miR-616-3p in gastric cancer. The results showed that miR-616-3p was up-regulated in cancer tissues. Higher expression of miR-616-3p in tumor tissues also predicted poor prognosis. Furthermore, loss- and gain-of-function in vitro revealed that miR-616-3p promoted angiogenesis and EMT in gastric cancer cells. Mechanistically, further analysis demonstrated that the effects of miR-616-3p on metastasis and angiogenesis occurred through the down-regulation of PTEN, a direct target of miR-616-3p. We propose that the restoration of PTEN expression may block miR-616-3p-induced EMT and angiogenesis. Collectively, our findings suggest that the miR-616-3p-PTEN signaling axis might be a potential therapeutic target for gastric cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

TGF-β plays a vital role in triple-negative breast cancer (TNBC) drug-resistance through regulating stemness, EMT and apoptosis

Highlights: • Acute epirubicin exposure induced TGF-β expression and breast cancer stemness. • Chronic epirubicin exposure established drug-resistant cell line MB-231/Epi. • MB-231/Epi enriched for TGF-β, CSC, anti-apoptosis, cycle arrest and EMT properties. • TGF-β play a vital role in regulating TNBC drug resistance. Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-β) is a multifunctional cytokine. In recent study, it appears that TGF-β influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected. We used epirubicin to treat MDA-MB-231 (MB-231) cells and found that TGF-β and breast cancer stem cell markers CD44{sup +}CD24{sup −} were increased and were dose-dependent of epirubicin. We established drug-resistant cell line from parental MB-231 cells by chronic treatment with low-concentration epirubicin. The MB-231/Epi cell line showed relatively slow growth rate with varied morphology. Transwell assay and drug sensitivity assay revealed that the malignant cell behaviors in terms of migration, invasion and epirubicin-resistant properties were markedly increased in the MB-231/Epi cells. Western blot, immunofluorescence assay, and flow cytometry were used to analyze the expression levels of the breast cancer stem cell markers, CD44 and CD24. Mammospheres assay showed that the stemness of MB-231/Epi was increased compared to their parental cells. Interestingly, MB-231/Epi cells showed different expression levels of apoptosis-related markers: Bcl2, Bax; EMT-related markers E-cadherin, N-cadherin and cell cycle-related marker cyclinD1. These genes have all been shown to be regulated by the TGF-β pathway. Taken together, our findings suggest that TGF-β plays a vital role in TNBC epirubicin-resistance through regulating stemness, EMT and apoptosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Iron chelator-induced up-regulation of Ndrg1 inhibits proliferation and EMT process by targeting Wnt/β-catenin pathway in colon cancer cells

Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), as the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells. However, whether Dp44mT has anticancer effects in colon cancer cells is still unknown. Here, we investigated the antitumor action of Dp44mT in colon cancer and its underlying mechanisms, and the connections between Dp44mT and N-myc downstream-regulated genes 1(Ndrg1). We used cell viability, migration and invasion assay, flow cytometry, western blot and qRT-PCR to examine the anticancer effects of Dp44mT and Ndrg1. We found that Dp44mT suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells and over-expression of Ndrg1 also suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells. Dp44mT attenuated the TGF-β1-induced EMT in colon cancer cells, and Dp44mT could up-regulate Ndrg1 expression level. Overexpression of Ndrg1 attenuates the TGF-β1-induced EMT, Dp44mT and Ndrg1 suppressed EMT through activation of Wnt/β catenin signaling pathway. In conclusion, our data demonstrated that Dp44mT/Ndrg1 have effective anticancer capability in colon cancer cells and that may represent a promising treatment strategy for human colon cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

The emission of cerium oxide nanoparticles (CeO{sub 2}) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO{sub 2} induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO{sub 2}-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO{sub 2} (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO{sub 2} (3.5 mg/kg) exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO{sub 2}-exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO{sub 2} exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO{sub 2}-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO{sub 2} exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO{sub 2} nanoparticle exposure. - Highlights: • CeO{sub 2} exposure induced lung fibrosis. • CeO{sub 2} were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO{sub 2} caused ATII cell hypertrophy and hyperplasia and altered fibroblast function. • Increased α-SMA in CeO{sub 2}-exposed lung fibroblasts indicating myofibroblast formation. • CeO{sub 2} induced EMT in ATII cells demonstrated as increased α-SMA expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistance to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

AI-Based EMT Dynamic Model of PV Systems

Several electromagnetic transient (EMT) dynamic modeling methods are available to model systems like photovoltaic (PV) plants, wind power plants, variable-speed drives, among others. The methods include: (a) physics-based models and (b) data-driven models. The physics-based dynamic models may include high-fidelity switched system model and average-value model that both require the control algorithms included in the models. However, manufacturers typically prefer to provide black-box models to avoid disclosing proprietary. One of the solutions to prevent disclosing control algorithms is the use of data-driven dynamic EMT models of PV systems. In this paper, data-driven dynamic EMT model based on artificial intelligence (AI) algorithms are presented. The AI algorithms evaluated include convolutional neural networks, recurrent neural networks, and nonlinear auto-regressive exogenous model. Automation in generating data and training these models is also discussed in this paper. The results generated by the best AI algorithms have been observed to be greater than 95 % accurate.

Debnath, Suman↗
DOE OSTI2024

Reinforcement Learning-Based Approach for EMT Automation of Large-Scale PV Plants

In the pursuit of efficient and precise modeling of large-scale power systems, particularly utility-scale photovoltaic (PV) plants, Electromagnetic Transient (EMT) simulations play a crucial role. As utility-scale PV plants increase in size and complexity, traditional computational methods become inadequate, necessitating more advanced techniques. This paper highlights the progressive efforts made to accelerate EMT simulations. A novel continuous reinforcement learning (RL) strategy is explored to automate the differentiation and categorization of stiff and non-stiff differential algebraic equations (DAEs). The use of stiff and non-stiff integration methods applied to relevant parts of the DAEs assists with the speed-up of the simulations. The paper details the data acquisition, development and offline training of the RL model, leading to its validation that demonstrates a high precision in optimizing simulation methods. The proposed RL promises to significantly enhance the efficacy of EMT simulations, offering a robust framework for the future of power system analysis.

Xia, Qianxue↗
DOE OSTI2023

High-Performance Computing Based EMT Simulation of Large PV or Hybrid PV Plants

Faults in the transmission grid have led to reduced power generation from power electronics resources that are typically not connected to the faulted transmission line. In many of the cases, partial loss of power is observed within the power electronics resources like large photovoltaic (PV) power plants. This phenomena is not captured in existing simulation models and/or simulators. High-fidelity switched system electromagnetic transient (EMT) dynamic models of PV power plants can improve the fidelity of models available for accurate analysis of the impact on PV plants during simulation of faults. However, these models are extremely computationally expensive and take a long time to simulate. Long simulation times limit the ability to use these models as larger regions are studied in EMT simulations with more power electronics resources. In this paper, numerical simulation algorithms are combined with high-performance computing techniques and applied to the high-fidelity switched system EMT model of PV plants. Using these techniques, a speed-up of up to 58x is obtained, while preserving the accuracy of the simulation at greater than 98%.

Debnath, Suman↗
DOE OSTI2023

EMT and Phasor-Domain Co-simulation of a Low Frequency AC Transmission System for Offshore Wind Integration

This work investigates system level interactions of multi-terminal low frequency high-voltage alternating current (LF-HVac) system using back-to back converters and grid-level 60 Hz system. A co-simulation framework by integrating high- fidelity dynamic model of multi-terminal LF-HVac system in electromagnetic transient (EMT) simulation platform and phasor model of IEEE 39 bus system in transient-stability (phasor) program. The co-simulation framework for multi-terminal LF- HVac system with offshore wind integrated in a bulk power system is developed successfully and its steady state and dynamic operation is demonstrated and compared with EMT simulation. The co-simulation results show accurate representation of the dynamic responses with reduced computation burden and time compared to EMT platform.

low-frequency transmission, co-simulation, electro↗
DOE OSTI2025

RE-INTEGRATE EMT Simulation Software: Graph Convolutional Network for Sparse Matrix Pattern Detection

The increasing complexity of power networks, driven by proliferation of inverters, presents analytical challenges that simplified models often fail to capture, necessitating Electromagnetic Transient (EMT) simulations. EMT models are represented as discretized differential-algebraic equations (DAEs), forming a linear system Ax = b that is computationally intensive to solve. Due to inherent sparsity of adjacency matrix A, distinct patterns emerge that, when accurately identified, enable efficient solver selection to minimize computation time. However, identifying ideal pattern is complicated by numerous reordering algorithms and limited structural insights. To address this, we introduce a Graph Convolutional Network (GCN) model for classifying sparse matrix patterns common in power system analysis. The model, achieving 96% test accuracy, is validated using PV plant models of 125 MW capacities connected to New England 39-bus transmission system (TS), and further scaled to a 4,992-bus network with 384 PV plants, yielding 191, 616 × 191, 616 sized A matrix. For all cases, the GCN model accurately identifies the matrix’s intrinsic sparse pattern, demonstrating its potential to enhance solver performance in EMT analysis.

Hossain, Md Rifat [Florida International Universit↗
DOE OSTI2020

Hybrid EMT-TS Simulation Strategies to Study High Bandwidth MMC-Based HVdc Systems

Modular multilevel converters (MMCs) are widely used in the design of modern high-voltage direct current (HVdc) transmission system. High-fidelity dynamic models of MMCs-based HVdc system require small simulation time step and can be accurately modeled in electro-magnetic transient (EMT) simulation programs. The EMT program exhibits slow simulation speed and limitation on the size of the model and brings certain challenges to test the high-fidelity HVdc model in system-level simulations. This paper presents the design and implementation of a hybrid simulation framework, which enables the co-simulation of the EMT model of Atlanta-Orlando HVdc line and the transient stability (TS) model of the entire Eastern Interconnection system. This paper also introduces the implementation of two high-fidelity HVdc line models simulated at different time steps and discusses a dedicated method for sizing the buffer areas on both sides of the HVdc line. The simulation results of the two HVdc models with different sizes of buffer areas are presented and compared.

Liu, Yuan↗
DOE OSTI2025

RE-INTEGRATE EMT Simulation Tool: Input Data Processing Layer for Bulk Power System

This paper introduces an advanced input data processing layer for EMT simulations of large-scale bulk power systems. The paper proposes two versions of the RE-INTEGRATE EMT simulation tool, RE-INTEGRATE Gen-0 and RE-INTEGRATE Gen-1, which are developed to enhance simulation generalizability, scalability, and accuracy. The framework leverages a generic class design for components to incorporate linear equations, which are generated by discretizing the Differential-Algebraic Equations (DAEs) that represent the dynamics of the components. In addition, the framework employs a parsing algorithm that parses a power system’s raw and dyr files to generate a connectivity graph which is then traversed to form the overall system’s dynamics. The proposed input data processing layer is used to simulate the IEEE 39-bus test system. The obtained results demonstrate the framework’s capability to achieve simulation scalability and accuracy. Further, the results indicate that EMT simulations performed using the proposed automations can effectively handle complex grid configurations.

Mishra, Rahul [ORNL] (ORCID:0000000328205932)↗
DOE OSTI2025

Assessing Dynamic Behaviors in Converter- Dominated Power Systems via RMS and EMT Simulations: A Study of Hawaii’s NELHA Microgrid

The transition from conventional power systems to converter-based microgrids has significantly advanced sustainability, clean energy integration, and operational reliability. However, this paradigm shift introduces operational challenges due to the intermittent nature of renewable energy sources and the non-linear characteristics of power electronic loads, inducing voltage fluctuations and harmonic distortions that complicate voltage and frequency regulation. Accurate dynamic modeling is hypothesized to be critical for capturing such effects, enabling reliable simulation and control strategy development. This study introduces an innovative dynamic modeling framework for a real-world converter-based microgrid, utilizing both root mean square (RMS) and electromagnetic transient (EMT) simulation methods. The microgrid was modeled in DIgSILENT PowerFactory, with simulations calibrated against high-resolution field measurements from SEL-735 power quality meters. Results show that RMS simulations effectively characterize steady-state dynamics, while EMT simulations are essential for capturing high-frequency transients and non-linear effects from photovoltaic inverters and variable frequency drives (VFDs). This complementary approach provides a comprehensive understanding of microgrid behavior, providing critical insights for improving simulation accuracy, advancing protection schemes, and improving resilience in future low-inertia power networks.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2018

A Novel Interfacing Technique for Distributed Hybrid Simulations Combining EMT and Transient Stability Models

With steady increase of power electronic devices and nonlinear dynamic loads in large scale AC/DC systems, the traditional hybrid simulation method, which incorporates these components into a single EMT subsystem and hence causes great difficulty for network partitioning and significant deterioration in simulation efficiency. To resolve these issues, a novel distributed hybrid simulation method is proposed in this paper. The key to realize this method is a distinct interfacing technique, which includes: i) a new approach based on the two-level Schur complement to update the interfaces by taking full consideration of the couplings between different EMT subsystems; and ii) a combined interaction protocol to further improve the efficiency while guaranteeing the simulation accuracy. The advantages of the proposed method in terms of both efficiency and accuracy have been verified by using it for the simulation study of an AC/DC hybrid system including a two-terminal VSC-HVDC and nonlinear dynamic loads.

Distributed hybrid simulation↗