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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 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction

Highlights: • Chetomin induced apoptosis in human triple-negative breast cancer cells. • Chetomin promoted ER stress and cellular calcium overload. • Chetomin mediated mitochondrial dysfunction triggered intrinsic pathway of cell death. • Chetomin inhibited PI3K/mTOR pathways. Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay. It exhibited antiproliferative response and induced apoptosis in both the cell types. Cell cycle analysis revealed that it increases the sub G0/G1 phase cell population. Modulation of mitochondrial membrane potential, activation of caspase 3/7 and a remarkable increase in the expression of cleaved PARP and increased chromatin condensation was observed after CHET treatment in MDA-MB-231 and MDA-MB-468 cells. Additionally, an elevated level of intracellular Ca{sup 2+} played an important role in CHET mediated cell death response. Calcium overload in mitochondria led to release of cytochrome c which in turn triggered caspase-3 mediated cell death. Inhibition of calcium signalling using BAPTA-AM reduced apoptosis confirming the involvement of calcium signalling in CHET induced cell death. Chetomin also inhibited PI3K/mTOR cell survival pathway in human TNBC cells. The overall findings suggest that Chetomin inhibited the growth of human TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling and could be used as a novel chemotherapeutic agent for the treatment of human TNBC in future.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

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

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

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Metal status in human endometrium: Relation to cigarette smoking and histological lesions

Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility. - Highlights: • Cd, Cr, Ni, Pb and Zn are detectable in human endometrium. • Mean metal content in human endometrium decreases in Cr>Pb>Zn>Ni>Cd order. • Cigarettes smoking increases endometrial content of Cd and Pb. • Lesioned endometrial tissue was characterized by higher metal contents.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Shifting temporal dynamics of human mobility in the United States

In this paper we analyze the average hourly temporal dynamics of human mobility in the United States from 2019 to 2020. We discuss how large decreases in human mobility nonuniformly effect the daily temporal dynamics of aggregate human behavior. The data used are weekly activity patterns for POIs from 2019 to 2020 in the United States, provided by SafeGraph and made openly available to academic and research institutions. We use clustering methods to create metrics describing how human activity changes throughout the day/week at the county and national levels. In response to significant mobility reductions starting March 2020, daily temporal patterns of human activity changed nonuniformly. Morning activity started later, and evening activity started earlier in 2020 compared to 2019, and temporal behavioral patterns on weekdays began to look more similar to weekends. The changes in daily temporal behavior persisted throughout the year even as total mobility levels recovered. The results provide insights on the changes in human behavior in response covid-19 policies and illustrate influences on social systems, health, and transportation networks.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2015

Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation. • Findings suggest dual functions of APOE for lipid accumulation and differentiation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Establishment of FXS-A9 panel with a single human X chromosome from fragile X syndrome-associated individual

Highlights: • We established mouse A9 cells with human X chromosome from FXS carrier and patient. • FXS-associated CGG repeats were stably maintained in established rodent cells. • Epigenetic status of CGG repeat region were maintained in established rodent cells. • Human FMR1 expression in these cells was according to each CGG repeat length. Fragile X syndrome (FXS) is the most common inheritable form of intellectual disability. FMR1, the gene responsible for FXS, is located on human chromosome Xq27.3 and contains a stretch of CGG trinucleotide repeats in its 5′ untranslated region. FXS is caused by CGG repeats that expand beyond 200, resulting in FMR1 silencing via promoter hypermethylation. The molecular mechanism underlying CGG repeat expansion, a fundamental cause of FXS, remains poorly understood, partly due to a lack of experimental systems. Accumulated evidence indicates that the large chromosomal region flanking a CGG repeat is critical for repeat dynamics. In the present study, we isolated and introduced whole human X chromosomes from healthy, FXS premutation carriers, or FXS patients who carried disease condition-associated CGG repeat lengths, into mouse A9 cells via microcell-mediated chromosome transfer. The CGG repeat length-associated methylation status and human FMR1 expression in these monochromosomal hybrid cells mimicked those in humans. Thus, this set of A9 cells containing CGG repeats from three different origins (FXS-A9 panel) may provide a valuable resource for investigating a series of genetic and epigenetic CGG repeat dynamics during FXS pathogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

A Feasibility Study on the Integration of Human Performance Data From Diverse Sources Based on the Complexity of a Proceduralized Task

Securing the safety of socio-technical systems including nuclear facilities is the upmost goal to ensure their sustainability because historical records demonstrate that the performance degradation of human operators (e.g., human errors) is one of the crucial contributors to the occurrence of unexpected events resulting in extensive casualties and financial losses. This implies that the collection of human performance data in diverse conditions with which they could be faced during the operation of nuclear facilities. As this collection requires significant resources, it is necessary to resolve how to accomplish it with limited resources. To address this challenge, as suggested in the SHEEP framework, it is indispensable to extract valuable insights after integrating various kinds of human performance data obtained from different sources. However, a practical method to soundly integrate them seems to be still incomplete. Accordingly, the applicability of TACOM (Task Complexity) measure is investigated as a tool to identify useful information based on the integration of human performance data observed from different simulation conditions. As a result, it is expected that the TACOM measure would play an important role in addressing the technical challenge in securing human performance data.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Characterizing Interaction Uncertainty in Human-Machine Teams

With the increasing use and adoption of artificial intelligence (AI), the reliability of modern data systems will be driven by a tighter teaming between human experts and intelligent machine teammates. As in the case of human-human teams, the success of human-machine teams will also rely on clear communication about mutual goals and actions. In this paper, we combine related literature from cognitive psychology, human-machine teaming, uncertainty in data analysis, and multi-agent systems to propose a new form of uncertainty: interaction uncertainty for characterizing bidirectional communication in human-machine teams. We map the causes and effects of interaction uncertainty and outline potential ways to mitigate uncertainty for mutual trust in a high-consequence real-world scenario.

uncertainty, data analytics, interaction, trust, h↗
DOE OSTI2014

A Framework for Human Performance Criteria for Advanced Reactor Operational Concepts

This report supports the determination of new Operational Concept models needed in support of the operational design of new reactors. The objective of this research is to establish the technical bases for human performance and human performance criteria frameworks, models, and guidance for operational concepts for advanced reactor designs. The report includes a discussion of operating principles for advanced reactors, the human performance issues and requirements for human performance based upon work domain analysis and current regulatory requirements, and a description of general human performance criteria. The major findings and key observations to date are that there is some operating experience that informs operational concepts for baseline designs for SFR and HGTRs, with the Experimental Breeder Reactor-II (EBR-II) as a best-case predecessor design. This report summarizes the theoretical and operational foundations for the development of a framework and model for human performance criteria that will influence the development of future Operational Concepts. The report also highlights issues associated with advanced reactor design and clarifies and codifies the identified aspects of technology and operating scenarios.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2023

Human Factors for Advanced Reactors

Existing light water reactors in the U.S. are primarily large baseload electricity generating facilities. The concept of operations for these plants remains largely unchanged since the advent of commercial nuclear power—the main control room serves as the hub of plant activities and is staffed with multiple licensed operators who work in tandem under the shift supervisor, and staff such as field workers support the control room remotely. While newer plants have brought the advent of digital human-machine interfaces to replace earlier analog and mechanical instrumentation and controls, much of the control process remains unchanged and manual. It is simply a newer version of legacy concepts. Advanced reactors potentially bring considerable changes to the size, fuel type, automation, and staffing of nuclear power plants, necessitating a fundamental shift not just from analog to digital, but further from human to automation, from onsite to remote, from control to monitoring, and from many to few operators. Despite this multitude of parallel evolutions in reactor designs, many of the vendors developing the next generation of reactors represent smaller research and development enterprises. It is therefore not feasible to address all aspects of plant design at the same time. In particular, the competing design aspects of new reactors present a significant challenge to the development of robust and human factored systems at the plant. As vendors develop new reactor designs, much of the early focus is naturally on the fuel and reactor system technology. Looming behind these early advances is the daunting prospect of first-of-a-kind control concepts that have not yet been developed or validated. A failure to address the human element of reactor design early will lead to missed opportunities. The quickest development process is the replication of existing concepts of operations at legacy plants, even when such systems were long ago surpassed by better human-machine technologies outside the nuclear industry. Conversely, attempting to undertake novel concepts of operations late in the design life cycle of a plant could result in protracted development efforts and delays in licensing and deployment. This does not have to happen, and it is imperative that human factors be considered now, early in the design of new reactors.

99 GENERAL AND MISCELLANEOUS↗
NASA NTRS1999

A large blood pressure-raising effect of nitric oxide synthase inhibition in humans

In experimental animals, systemic administration of nitric oxide synthase (NOS) inhibitors causes large increases in blood pressure that are in part sympathetically mediated. The aim of this study was to determine the extent to which these conclusions can be extrapolated to humans. In healthy normotensive humans, we measured blood pressure in response to two NOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), the latter of which recently became available for use in humans. The major new findings are 3-fold. First, L-NAME produced robust increases in blood pressure that were more than 2 times larger than those previously reported in humans with L-NMMA and approximated those seen in experimental animals. L-NAME (4 mg/kg) raised mean arterial pressure by 24+/-2 mm Hg (n=27, P<0.001), whereas in subjects who received both inhibitors, a 12-fold higher dose of L-NMMA (50 mg/kg) raised mean arterial pressure by 15+/-2 mm Hg (n=4, P<0.05 vs L-NAME). Second, the L-NAME-induced increases in blood pressure were caused specifically by NOS inhibition because they were reversed by L-arginine (200 mg/kg, n=12) but not D-arginine (200 mg/kg, n=6) and because NG-nitro-D-arginine methyl ester (4 mg/kg, n=5) had no effect on blood pressure. Third, in humans, there is an important sympathetic component to the blood pressure-raising effect of NOS inhibition. alpha-Adrenergic blockade with phentolamine (0.2 mg/kg, n=9) attenuated the L-NAME-induced increase in blood pressure by 40% (P<0.05). From these data, we conclude that pharmacological inhibition of NOS causes large increases in blood pressure that are in part sympathetically mediated in humans as well as experimental animals.

Non-NASA Center↗
NASA NTRS1999

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Non-NASA Center↗
NASA NTRS1999

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗
NASA NTRS2004

Robots and humans: synergy in planetary exploration

How will humans and robots cooperate in future planetary exploration? Are humans and robots fundamentally separate modes of exploration, or can humans and robots work together to synergistically explore the solar system? It is proposed that humans and robots can work together in exploring the planets by use of telerobotic operation to expand the function and usefulness of human explorers, and to extend the range of human exploration to hostile environments. Published by Elsevier Ltd.

Robotics↗
NASA NTRS2015

Human Performance Considerations for Remotely Piloted Aircraft Systems (RPAS)

Successful integration of Remotely Piloted Aircraft Systems (RPAS) into civil airspace will not only require solutions to technical challenges, but will also require that the design and operation of RPAS take into account human limitations and capabilities. Human factors can affect overall system performance whenever the system relies on people to interact with another element of the system. Four types of broad interactions can be described. These are (1) interactions between people and hardware, such as controls and displays; (2) human use of procedures and documentation; (3) impact of the task environment, including lighting, noise and monotony; and lastly, (4) interactions between operational personnel, including communication and coordination. In addition to the human factors that have been identified for conventional aviation, RPAS operations introduce a set of unique human challenges. The purpose of document is to raise human factors issues for consideration by workgroups of the ICAO RPAS panel as they work to develop guidance material and additions to ICAO annexes. It is anticipated that the content of this document will be revised and updated as the work of the panel progresses.

ICAO↗
NASA NTRS2016

Human Factors in Aeronautics at NASA

This is a briefing to a regularly meeting DoD group called the Human Systems Community of Interest: Mission Effectiveness. I was asked to address human factors in aeronautics at NASA. (Exploration (space) human factors has apparently already been covered.) The briefing describes human factors organizations at NASA Ames and Langley. It then summarizes some aeronautics tasks that involve the application of human factors in the development of specific tools and capabilities. The tasks covered include aircrew checklists, dispatch operations, Playbook, Dynamic Weather Routes, Traffic Aware Strategic Aircrew Requests, and Airplane State Awareness and Prediction Technologies. I mention that most of our aeronautics work involves human factors as embedded in development tasks rather than basic research.

NASA↗
NASA NTRSDate not supplied

Planned Investigations to Address Acute Central Nervous System Effects of Space Radiation Exposure with Human Performance Data

This work intends to generate evidence of acute, incremental human performance decrement similar to that due to space radiation andits impacts on the brain, to accompany ongoing human performance modeling work. The planned work will explore the boundaries of human behavioral and performance decrement after exposure to stress, which may be expected based in part on rodent responses found afterexposure to ionizing radiation. The collection of evidence via simulation studies can characterize real human errors toward determining what stress levels lead to significantly-low levels of performance (below permissible outcome limits) which would imperilmission accomplishment. If mission-relevant animal-study-linked tasks are used, human and animal performance levels may be aligned to enable quantitative assignment of permissible exposure limits based on animal exposure studies. Ultimately, a transfer function between the performances of exposed rodents and humans under stress can be developed using shared impairment mechanisms.

human performance↗
NASA NTRSDate not supplied

Planned Investigations to Address Acute Central Nervous System Effects of Space Radiation Exposure with Human Performance Data

This work intends to generate evidence of acute, incremental human performance decrement similar to that due to space radiation and its impacts on the brain, to accompany ongoing human performance modeling work. The planned work will explore the boundaries of human behavioral and performance decrement after expo-sure to stress, which may be expected based in part on rodent responses found after exposure to ionizing radiation. The collection of evidence via simulation studies can characterize real human errors toward determining what stress levels lead to significantly-low levels of performance (below permissible outcome limits) which would imperil mission accomplishment. If mission-relevant yet animal-study-linked tasks are used, human and animal performance levels may be aligned to enable quantitative assignment of permissible exposure limits based on animal exposure studies. Ultimately, a transfer function between the performances of exposed rodents and humans under stress can be developed using shared impairment mechanisms.

human performance↗