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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

IR spectroscopic characteristics of cell cycle and cell death probed by synchrotron radiation based Fourier transform IR spectromicroscopy

Synchrotron radiation based Fourier transform IR (SR-FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR-FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR-90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G(1)-phase to the S-phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl C===O peak at 1743 cm(-1) is observed. Copyright John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 329-335, 2000.

Non-NASA Center↗
DOE OSTI2025

Automated Label‐Free Assay for Viral Detection and Inhibitor Screening via Biomembrane‐Functionalized Microelectrode Arrays

Most virus infection assays have indirect readout such as virus number following entry (e.g., PCR, cell lysis). While effective, these technologies are labor‐intensive, require specialized environments (e.g., sterile or RNA‐free), and detect later‐stage viral events like lysis or cell death, lacking sensitivity to early fusion events. To address these limitations, we present biologically relevant 2D membrane materials, host‐cell‐derived supported lipid bilayers (hcd‐SLBs), integrated with organic microelectrode arrays (OMEAs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) fusion. By overexpressing angiotensin‐converting enzyme 2 (ACE2) receptors on the native membranes, the platform functions as a viral sensor capable of detecting virus pseudo particles (VPPs) through the late pathway. Additionally, hcd‐SLBs extracted from human lung epithelium expressing native ACE2 detect fusion events through the early pathway. The platform's utility as a drug‐screening tool is demonstrated by testing antibodies targeting either the ACE2 on the host membrane or the viral spike (S) proteins. To enhance the throughput, microfluidics are integrated for automation and OMEAs are incorporated within each channel, miniaturizing the testing units. This system supports high‐throughput data generation, automation, and scalability, providing an efficient platform for viral fusion detection that advances the study of pathogen‐host interactions and accelerates antiviral drug discovery.

Biology↗
DOE OSTI2022

Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 “critical” (in the intensive care unit under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2021

simcov v0.1

Simcov is an agent-based model of the spread of viral infections and the immune response in human lung at the cellular level. It is designed to scale well on HPC systems. No other software like it currently exists.

Hofmeyr, Steven↗
DOE OSTI2025

Controlling Host Responses to Infection

Pathogen invasion of host cells causes a myriad of functional changes including alterations of chromatin accessibility often limiting defense responses, shunting of cellular resources to centers of viral replication, and rearrangement of intracellular membranes to facilitate genome reproduction and progeny release. Systems biology approaches provide global snapshots of pathogen induced changes following infection and provide a variety of tools to begin to define how cellular homeostasis is disrupted, but improvements on these tools are required to determine how cellular functions are altered post infection. Chromatin accessibility techniques, biochemical assays to assess the activity of epigenetic enzymes, scalable sample collection platforms, and activity-based probes were used to characterize how human respiratory viruses modify host responses in infected human lungs over time. These studies enhanced our knowledge of how pathogens usurp the host environment during infection and identify additional targets for future evaluations of medical countermeasures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is characterized by an excessive accumulation of extracellular matrix (ECM) proteins (e.g. collagens) in the parenchyma, which ultimately leads to respiratory failure and death. While current therapies exist to slow the progression, no therapies are available to resolve fibrosis. We characterized the O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT)/O-GlcNAc axis in IPF using single-cell RNA-sequencing (scRNA-seq) data and human lung sections and isolated fibroblasts from IPF and non-IPF donors. The underlying mechanism(s) of IPF were further investigated using multiple experimental models to modulate collagen expression and accumulation by genetically and pharmacologically targeting OGT. Furthermore, we hone in on the transforming growth factor-beta (TGF-β) effector molecule, Smad3, by co-expressing it with OGT to determine if it is modified and its subsequent effect on Smad3 activation. We found that OGT and O-GlcNAc levels are upregulated in patients with IPF compared to non-IPF. We report that the OGT regulates collagen deposition and fibrosis resolution, which is an evolutionarily conserved process demonstrated across multiple species. Co-expression of OGT and Smad3 showed that Smad3 is O-GlcNAc modified. Blocking OGT activity resulted in decreased phosphorylation at Ser-423/425 of Smad3 attenuating the effects of TGF-β1 induced collagen expression/deposition. OGT inhibition or knockdown successfully blocked and reversed collagen expression and accumulation, respectively. Smad3 is discovered to be a substrate of OGT and its O-GlcNAc modification(s) directly affects its phosphorylation state. These data identify OGT as a potential target in pulmonary fibrosis resolution, as well as other diseases that might have aberrant ECM/collagen accumulation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1973

Recent NASA aerospace medicine technology developments

Areas of life science are being studied to obtain baseline data, strategies, and technology to permit life research in the space environment. The reactions of the cardiovascular system to prolonged weightlessness are also being investigated. Particle deposition in the human lung, independent respiratory support system, food technology, and remotely controlled manipulators are mentioned briefly.

Jones, W. L.↗
NASA NTRS1973

Detection techniques for tenuous planetary atmospheres

The research performed during this period is reported. The studies discussed include: dust grinding and electrification, effects of metallic impurities on exoelectron emission, the connection between the charge acquired by the dust and the effect of the dust on human lung tissue. A list of publications generated by this research is included.

Hoenig, S. A.↗
NASA NTRS1972

Effects of geophysical extra-terrestrial and terrestrial physical stimuli on living organisms - Effects of gravity fields on living organisms

The biologic effects of greatly reduced gravity resulting from space flight are examined. Aspects of U.S. space biology during the period from 1960 to 1972 are discussed, giving attention to the Discoverer satellites, the Gemini series, the OV1-4 satellite, the biosatellite project, the orbiting frog otolith experiment, and the Apollo program. Other studies considered are related to the effects of galactic particles on nonproliferating cells, a recoverable tissue culture experiment, cell cycle maintenance in human lung cells, and effects of space flight on circadian rhythms. Viking will land on the planet Mars in 1975 in search for life forms.

Saunders, R. J. F.↗
NASA NTRS1978

Monitoring the state of the human airways by analysis of respiratory sound

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Hardin, J. C.↗
NASA NTRS1980

Genesis of breath sounds-Preliminary verification of theory

Experimental results are presented which tend to validate a previously developed theory of sound production in the human lung over a particular Reynolds number range. In addition, a new, presently nonunderstood, phenomenon was observed at higher Reynolds number. These results, which show how sound generation in the lung depends upon the physiologically important variables of volume flow rate and bronchial diameter, have potentially important application in noninvasive lung examination and the diagnosis of lung disease.

Patterson, J. L.↗
NASA NTRS1994

Estimates of cellular mutagenesis from cosmic rays

A parametric track structure model is used to estimate the cross section as a function of particle velocity and charge for mutations at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus in human fibroblast cell cultures. Experiments that report the fraction of mutations per surviving cell for human lung and skin fibroblast cells indicate small differences in the mutation cross section for these two cell lines when differences in inactivation rates between these cell lines are considered. Using models of cosmic ray transport, the mutation rate at the HGPRT locus is estimated for cell cultures in space flight and rates of about 2 to 10 x 10(exp -6) per year are found for typical spacecraft shielding. A discussion of how model assumptions may alter the predictions is also presented.

Cucinotta, Francis A.↗
NASA NTRS2006

Lunar Dust Activation and Related Studies

The primary objective of the presentation is to identify a set of experiments to activate the lunar dust and monitor the mode of deactivation process using various analytical methods. To satisfy the objective, a large set of experiments will be carried out using lunar dust stimulant (JSC-1a-vf obtained from Dr. V. Carter from University of Texas at Dallas) to optimize the methodology. After refining the methodology to carry out the experiments using the simulant, real lunar dust will be used to obtain the necessary results. The secondary objective of the presentation is to identify a set of experiments to assess the potential toxicity of the dust using cellular systems. One of the cell lines that we identified is WI-38 human lung cell line.

Jeevarajan, Antony↗
NASA NTRS2009

Effect of Lunar Dust Simulant on Human Epithelial Cell Lines

The purpose of this project is to assess the potential toxicity of lunar dust to cause the release of pro-inflammatory cytokines by human lung cells. Some of this dust is on the scale of 1-2 micrometers and could enter the lungs when astronauts track dust into the habitat and inhale it. This could be a serious problem as NASA plans on going back to the moon for an extended period of time. Literature shows that quartz, which has a known cytoxicity, can cause acute cases of silicosis within 6 months, and in most cases cause silicosis after 3 years. The activation of lunar dust through impacts creates surface based radicals which, upon contact with water create hydroxl radicals and peroxyl radicals which are very reactive and potentially might even be as cytotoxic as quartz. These radicals could then react with lung cells to produce pro-inflammatory mediators such as interleukin-6 and interleukin-8, and TNF-alpha.

Myers, Nicholas J.↗
NASA NTRS2015

Summer 2015 Internship Abstract

Green fluorescent protein (GFP) visually shows the expression of proteins by fluorescing when exposed to certain wavelengths of light. The GFP in this experiment was used to identify cells actively releasing viruses. The experiment focused on the effect of microgravity on the GFP expression of Akata B-cells infected with Epstein Barr Virus (EBV). Two flasks were prepared with 30 million cells each and two bioreactors were prepared with 50 million cells each. All four cultures were incubated for 16 days and fed every four days. Cellometer readings were taken on the feeding days to find cell size, viability, and GFP expression. In addition, the cells were treated with Propodium monoazide (PMA) and run through real time PCR to determine viral load on the feeding days. On the International Space Station air samples are taken to analyze the bacterial and fungal organisms in the air. The Sartorius Portable Airport is being investigated for potential use on the ISS to analyze for viral content in the air. Multiple samples were taken around Johnson Space Center building 37 and in Clear Lake Pediatric Clinic. The filter used was the gelatin membrane filter and the DNA was extracted directly from the filter. The DNA was then run through real time PCR for Varicella Zoster Virus (VZV) and EBV as well as GAPDH to test for the presence of DNA. The results so far have shown low DNA yield and no positive results for VZV or EBV. Further inquiry involves accurately replicating an atmosphere with high viral load from saliva as would be found on the ISS to run the air sampler in. Another line of research is stress hormones that may be correlated to the reactivation of latent viruses. The stress hormones from saliva samples are analyzed rather than blood samples. The quantity found in saliva shows the quantity of the hormones actually attached to cells and causing a reaction, whereas in the blood the quantity of hormones is the total amount released to cause a reaction. The particular hormones tested for were cortisol, alpha-amylase, and DHEA. The DHEA was very high in the two control samples tested. Regularly, samples came into the lab from local clinics to be tested for various viruses. Saliva, blood, body scrapes, and tears were received from the clinics and then run for VZV, EBV, and Human Simplex Virus 1 (HSV-1) with the results then reported back to the clinician. Blood, saliva, and urine from astronauts were also tested for viruses and logged. In addition, several cell cultures were brought up and grown, including adherent Human Lung Fibroblast (HFL) cells infected with VZV, and Akata B-cells infected with EBV.

Smith, Courtney↗
NASA NTRS1998

Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations

We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

Clinical Trial↗
NASA NTRS2015

Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

Lam, C.‐W.↗
DOE OSTI2026

FTIR imaging identifies alterations in lung tissue structure and biochemical composition in human idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and fatal lung disease characterized by damage to the epithelial tissue and a reduced ability of the alveoli to repair themselves. This impaired repair process leads to abnormal accumulation of extracellular matrix (ECM), resulting in scarring and stiffening of lung tissue. Fourier transform infrared imaging (FTIRI) is a promising technique for imaging the biochemical changes related to fibrotic changes in a label-free and non-destructive manner, which can be analyzed to mark the progression of IPF. In this study, FTIRI was used to image human lung tissue biopsies with IPF and control biopsies without disease. In-depth spectral analyses were performed to observe the biochemical changes in the tissue composition using FTIRI. The parameters that were analyzed included collagen structure, total lipid content, lipid chain length, and phospholipids. Results showed a significant increase in lipid content in IPF compared to control, where long chain lipids dominated and phospholipids were reduced. Minor changes in collagen structure were also observed in IPF, likely attributed to the excess formation of extracellular matrix in the disease. These findings indicate that FTIRI has the potential to be a promising diagnostic technique to understand the molecular changes during IPF, as analysis of infrared data can reveal detailed biochemical information regarding disease progression and provide spatial insights on the molecular changes across the IPF lung tissue.

59 BASIC BIOLOGICAL SCIENCES↗