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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Cytotoxicity measurement of Bisphenol A (BPA) and its substitutes using human keratinocytes

Highlights: • BPA has been widely used in many plastic products despite it might be harmful to human health. • Many alternatives developed lack sufficient toxicity assessment. • BPA showed significantly higher cytotoxicity than its five substitutes. • CHDM and TPA might be suitable substitutes to replace BPA. Bisphenol-A (BPA) was first synthesized in the 1890s and has been used in many plastic products. However, BPA is known to act as an endocrine disruptor and has been found to be toxic to human health. Many alternative substances have been developed to replace BPA, but it is still widely used worldwide. In this study, we identified the potential cytotoxicity of BPA by evaluating toxicity using human keratinocytes. Also, we evaluated cytotoxicity of BPA substitutes to determine their suitability as an alternative to BPA. The proliferation assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and western blot analysis showed that BPA significantly affect cell viability, induction of apoptotic fraction and increased activation of DNA-damage marker protein. In addition, through the same experiments, the substitutes of BPA were shown to be significantly less toxic than BPA, and the least toxicity was observed with 1,4-cyclohexanedimethanol (CHDM) and terephthalic acid (TPA). In conclusion, this study suggests that cytotoxicity of BPA induces apoptosis of human keratinocytes, and that CHDM and TPA are the most suitable substitutes for BPA.

54 ENVIRONMENTAL SCIENCES↗
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 OSTI2025

Teleoperation of Construction Robots Using Human Interaction: Case Study Examples: Preprint

The integration of advanced teleoperation methods in construction robotics has the potential to enhance productivity and safety in demanding environments. Among different methods, hand gestures have emerged as an intuitive approach, enabling seamless communication between human operators and robotic systems. This study demonstrates the use of hand gestures for controlling a model robotic excavator and a virtual robotic arm in construction applications. Two case study examples are presented. In the first case study, a series of hand gestures are performed to control a model robotic excavator's bucket and arm movements. The second case study focuses on using hand gestures to control a virtual robotic arm to perform a material handling task in a simulated environment. In both cases, the performed hand gestures are all successfully captured and interpreted by the gesture-based teleoperation method to conduct the corresponding tasks, which demonstrates the application of the gesture-based control method for various types of construction robots. Also, the limitations of the gesture-based teleoperation method (e.g., recognition delay, sensitivity to motion outliers) are discussed. Future work will focus on developing a digital twin system to support gesture-based teleoperation for a wider range of construction robots.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2020

Linking Internal Dosimetries of the Propyl Metabolic Series in Rats and Humans Using Physiologically Based Pharmacokinetic (PBPK) Modeling

The metabolic series approach has successfully linked internal dosimetries of metabolically related compounds reducing cost and time for chemical risk assessments. Here, we developed a physiologically based pharmacokinetic (PBPK) model in rats and humans for the propyl metabolic series including propyl acetate, 1-propanol, propionaldehyde, and propionic acid. Manufacturers use these compounds as organic solvents and intermediates during chemical synthesis. Public exposures can occur through using consumer products containing propyl compounds like cosmetics, aerosol sprays, or foods. To develop the PBPK model, we measured in vitro metabolism of propyl acetate in blood and liver S9 fractions. We measured concentrations of propyl compounds in blood following intravenous (iv) infusion of 13C-propanol or 13C-propionic acid and closed chamber inhalation exposures to propyl acetate or propanol in rats. Using these studies and other published data, we modified an existing PBPK model for the butyl metabolic series to simulate time course concentrations of propyl compounds in rats and humans. Consistent with measured in vitro and in vivo data, the optimized propyl series model predicts rapid clearance of propyl acetate, higher concentrations of propanol in blood from propyl acetate inhalation compared to propanol inhalation, and low concentrations of propionic acid in blood from exposures to propyl acetate or propanol. Regulators can use this model as a tool for propyl compound risk assessment by linking internal dosimetries under various exposure scenarios.

Smith, Jordan N.↗
DOE OSTI2019

14 C-Cobalamin Absorption from Endogenously Labeled Chicken Eggs Assessed in Humans Using Accelerator Mass Spectrometry

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt ( 57 Co, 58 Co or 60 Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14 C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14 C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14 C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5–0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14 C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Biomarkers of exposure in environment-wide association studies – Opportunities to decode the exposome using human biomonitoring data

The European Union's 7th Framework Programme (EU's FP7) project HEALS – Health and Environment-wide Associations based on Large Population Surveys – aims a refinement of the methodology to elucidate the human exposome. Human biomonitoring (HBM) provides a valuable tool for understanding the magnitude of human exposure from all pathways and sources. However, availability of specific biomarkers of exposure (BoE) is limited.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

A spot test for determination of residual TBA levels in 18 F-radiotracers for human use using Dragendorff reagent

When utilizing [ 18 F]tetrabutylammonium fluoride ([ 18 F]TBAF) in the synthesis of 18 F-labeled radiotracers for clinical positron emission tomography (PET) imaging, it is necessary to confirm that residual TBA levels in formulated doses do not exceed established specifications (≤2.6 mg per patient dose). Historically this has been accomplished using HPLC, but this is time consuming for short-lived PET radiotracers and limited by the need for expensive equipment. This motivated us to introduce a TLC spot test for determining residual TBA, and we have developed a new method which employs the Dragendorff reagent. Herein we report details of the TLC method and use it to quantify residual TBA in different formulations of 6-[ 18 F]fluoro-DOPA.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Dual-Biometric Human Identification Using Radar Deep Transfer Learning

Accurate human identification using radar has a variety of potential applications, such as surveillance, access control and security checkpoints. Nevertheless, radar-based human identification has been limited to a few motion-based biometrics that are solely reliant on micro-Doppler signatures. This paper proposes for the first time the use of combined radar-based heart sound and gait signals as biometrics for human identification. The proposed methodology starts by converting the extracted biometric signatures collected from 18 subjects to images, and then an image augmentation technique is applied and the deep transfer learning is used to classify each subject. A validation accuracy of 58.7% and 96% is reported for the heart sound and gait biometrics, respectively. Next, the identification results of the two biometrics are combined using the joint probability mass function (PMF) method to report a 98% identification accuracy. To the best of our knowledge, this is the highest reported in the literature to date. Lastly, the trained networks are tested in an actual scenario while being used in an office access control platform to identify different human subjects. We report an accuracy of 76.25%.

47 OTHER INSTRUMENTATION↗
DOE OSTI2023

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, in this work, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β–mediated AML progression

Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The proinflammatory cytokine interleukin-1β (IL-1β) is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1β–upregulated ASF1B (antisilencing function-1B), a histone chaperone, in AML progenitors compared with healthy progenitors. ASF1B, along with its paralogous protein ASF1A, recruits H3-H4 histones onto the replication fork during S-phase, a process regulated by Tousled-like kinase 1 and 2 (TLKs). Although ASF1s and TLKs are known to be overexpressed in multiple solid tumors and associated with poor prognosis, their functional roles in hematopoiesis and inflammation-driven leukemia remain unexplored. In this study, we identify that ASF1s and TLKs are overexpressed in multiple genetic subtypes of AML. We demonstrate that depletion of ASF1s significantly reduces leukemic cell growth in both in vitro and in vivo models using human cells. Using a murine model, we show that overexpression of ASF1B accelerates leukemia progression. Moreover, Asf1b or Tlk2 deletion delayed leukemia progression, whereas these proteins are dispensable for normal hematopoiesis. Through proteomics and phosphoproteomics analyses, we uncover that the TLK-ASF1 pathway promotes leukemogenesis by affecting the cell cycle and DNA damage pathways. Collectively, our findings identify the TLK1-ASF1 pathway as a novel mediator of inflammatory signaling and a promising therapeutic target for AML treatment across diverse genetic subtypes. Finally, selective inhibition of this pathway offers potential opportunities to intervene effectively, address intratumoral heterogeneity, and ultimately improve clinical outcomes in AML.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Investigating the Influence of River Geomorphology on Human Presence Using Night Light Data: A Case Study in the Indus Basin

Human settlements have historically thrived near rivers due to enhanced navigation and trade, and the availability of water supply and resources. The use of night light data, representing economic activities, provides a novel approach to studying the interactions between human activity and rivers over time. Here, we use the Defense Meteorological Satellite Program (DMSP) stable night light data from 2000 to 2013 as a proxy for human presence and activities to quantify the statistical relationships between night light presence and intensity in the Indus Basin, Asia. We test how these data are affected by proximity to trunk channels and by channel type (single/multi-thread) in the study area. We find that night light presence is enhanced by 26% within a 0 to 5 km proximity range of the Indus River and its tributaries, relative to the basin as a whole. We interpret this to represent increased human presence and activity within this zone. However, the mean intensity is lower near the river and higher away from the river, signifying denser settlements, such as towns and cities, which are preferentially located away from the Indus and its tributaries. Moreover, the enhancement of lit pixels signifying human presence and activities is increased by 18% near single-thread sections of the Indus River, compared to segments of the Indus displaying multi-thread morphologies. We suggest that this is due to the enhanced stability of single-threaded channels, relative to mobile multi-threaded channel reaches. This study demonstrates how night lights are an important tool in studying the relationship between human presence and river dynamics in large catchments such as the Indus, and we suggest that these data will have an important role in assessing differential flood spatial and social vulnerability at a regional scale.

Environmental Sciences & Ecology↗
DOE OSTI2021

Modeling FLEX Human Actions Using the EMRALD Dynamic Risk Assessment Tool

Most current efforts have modified and applied existing human reliability analysis (HRA) methods to treat human actions related to beyond-design-basis external events in which diverse and flexible coping strategies (FLEX) equipment would be deployed. However, many questions remain regarding the suitability of legacy HRA methods to address FLEX human actions, sparking the need for a new method of reasonably evaluating them. In this context, Idaho National Laboratory (INL) researched a relatively new approach to treating FLEX human actions via Event Modeling Risk Assessment Using Linked Diagrams (EMRALD) software. EMRALD was developed to support the increasing need for dynamic probabilistic risk assessment (PRA) models that can respond to evolving plant conditions during simulations. A couple benefits were identified when analyzing FLEX human actions through this software. In general, it is especially useful for evaluating a strategy’s feasibility, including FLEX human actions that require a relatively long time to perform. In this paper, we suggest how FLEX human actions can be modeled using the EMRALD software. Two different HRA modeling approaches using EMRALD are introduced: (1) procedure-based modeling and (2) PRA/HRA-based modeling. The former approach was introduced in the authors’ previous paper, whereas this paper mainly discusses how the latter approach works for an extended loss of AC power (ELAP) scenario with relevant procedures and PRA models. A hybrid method combining the two modeling approaches is introduced at the paper’s conclusion.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models.

Cell Biology↗