Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “LUNGS”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03 - 0.80 Gy). Female CB6F1 mice were irradiated with low single doses of either oxygen, silicon, titanium, or iron ions at various energies to cover a range of dose-averaged LET values from 0.2 - 193 keV/µm, using 137Cs γ-rays as the reference radiation. Sham-treated controls were included in each individual experiment totally 398 animals across the 5 studies reported. Based on power calculations, between 40 - 156 mice were included in each of the treatment groups. Tumor prevalence at 16 months after radiation exposure was determined and compared to the age-matched, sham-treated animals. Results indicate that lung tumor prevalence is non-linear as a function of dose with suggestions of threshold doses depending on the LET of the beams. Histopathological evaluations of the tumors showed that the majority of tumors were benign bronchioloalveolar adenomas with occasional carcinomas or lymphosarcomas which may have resulted from metastases from other sites.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Chronic obstructive pulmonary disease among former United States Department of Energy workers: comorbidities and lung function changes

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in the United States and is frequently associated with multiple comorbidities which lead to poor COPD outcomes in the general population. However, little is known regarding COPD comorbidities in occupational cohorts whose exposure experiences could result in differences in comorbidities compared to the general population. These differences may also be important for assessing COPD outcomes such as lung function changes or decline. Therefore, the objectives of this study were to: (1) identify and describe clusters of COPD comorbidities among Department of Energy (DOE) former workers; (2) assess if the attributes of the identified clusters differ from those identified among the general population based on the published literature, and (3) identify predictors of lung function changes and decline among DOE former workers.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1999

Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.

NASA Discipline Cardiopulmonary↗
NASA NTRS1992

Stress failure of pulmonary capillaries: role in lung and heart disease

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Review↗
DOE OSTI2025

Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells

Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70-reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein–protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. As a result, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Influence of alveolar mixing and multiple breaths of aerosol intake on particle deposition in the human lungs

Predictive dosimetry models play an important role in assessing health effect of inhaled particulate matter and in optimizing delivery of inhaled pharmaceutical aerosols. Here, in this study, the commonly used 1D Multiple-Path Particle Dosimetry model (MPPD) was improved by including a mechanistically based model component for alveolar mixing of particles and by extending the model capabilities to account for multiple breaths of aerosol intake. These modifications increased the retained fraction of particles and consequently particle deposition predictions in the deep lung during tidal breathing. Comparison with an existing dataset (J. Aerosol Sci., 99:27-39, 2016) obtained under two breathing conditions referred to as slow and fast breathing showed significant differences in 1 µm particle deposition between predictions (slow: 30±1%, fast: 21±1%) and measurements (slow: 43±9%, fast: 30±5%) when the prior version of MPPD (single breath and no mixing, J. Aerosol Sci., 151:105647, 2021) was used. Adding a mixing model and multiple breaths moved the predictions (slow: 34±2%, fast:25±2%) closer to the range of deposition measurements. For 2.9 µm particles, predictions from both the original (slow: 70±2%, fast: 57±2%) and the revised MPPD model (slow: 71±2%, fast: 59±3%) compared well with experiments (slow: 67±8%, fast: 58±10%). This was expected as suspended fraction of 2.9 µm particles was small and thus the addition of alveolar mixing and multi breath capability only slightly increased the retained fraction for particles of this size and greater. The revised 1D model improves dose predictions in the deep lung and support human risk assessment from exposure to airborne particles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein

Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP–LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP–LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16-37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP–LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP–LNP complexes can expand the therapeutic potential of genome editing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Tumor-promoting UBR4 coordinates impaired mitophagy–associated senescence and lung adenocarcinoma pathogenesis

Cellular senescence, an irreversible cell cycle arrest, plays a pivotal role in development, aging, and tumor suppression. However, the fundamental pathway coordinating senescence and neoplastic transformation remains unclear. Here, we describe the tumorigenic involvement of ubiquitin protein ligase E3 component n-recognin 4 (UBR4), an E3 ubiquitin ligase of the N-degron pathway, in lung adenocarcinoma (LUAD). Public genome databases revealed high UBR4 expression in LUAD patients, associated with a dysregulated cell cycle and impaired mitochondrial homeostasis.UBR4knockout (ΔUBR4) in A549 lung cancer cells induced cellular senescence with defective mitochondria. Restoration of UBR4 or antioxidant treatment reversed the ΔUBR4 phenotypes caused by impaired mitophagy. Mitochondrial stress exacerbated mitochondrial dysfunction in ΔUBR4 cells, contributing to diverse cellular phenotypes. Additionally, ΔUBR4 cells exhibited substantially slow tumor growth in mouse xenograft models. In LUAD patients, UBR4 levels correlated with tumor stage, mitophagy markers, and poor survival. These findings suggest a tumor-promoting function of UBR4 in LUAD by regulating mitochondrial quality control. Further research into the pharmacological inhibition of UBR4 could open promising avenues for developing effective antitumor therapies targeting LUAD.

Science & Technology - Other Topics↗
DOE OSTI2021

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection and the magnitude and timing of the T cell immune response. When the branching airway structure of the lung is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed differential equation model. These results illustrate how realistic, spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

In vitro toxicity assessment of uranium particulates on different human lung epithelial cell models

Inhalation of uranium aerosols produced via human activities such as mining can pose a threat to human respiratory systems. Uranium oxide particulates emit short-range alpha particles that elicit DNA and direct damage, beyond associated physiochemical heavy-metal toxicity, to internal epithelial tissues. The availability of reliable in vitro models to study radiation exposure can greatly enhance our ability to understand and combat the biological impacts of exposure. However, the toxicological effects of alpha emissions and/or the oxidation states of uranium particulates vary across different human lung epithelial cell models and have not been systematically compared. We have endeavored to address this limitation by comparing impacts in three different human lung cell models: primary human bronchial and tracheal epithelial cells, primary human small airway epithelial cells, and human adenocarcinoma alveolar basal epithelial cells. Other studies have mainly investigated the toxicity of depleted uranium. Here, we compared the exposure of uranium oxide particulates (U 3 O 8 and UO 3 ) of different enrichment states on the chosen cell systems. Each cell model was exposed to 0.1, 1, 10, 50, 100, and 500 µg/mL of depleted U 3 O 8 , highly-enriched U 3 O 8 , and natural UO 3 particulates for 24 hours in submerged monolayer cultures. We compared viability and superoxide dismutase activity results across cell lines and uranium enrichment/ oxidative states. The results showed that 1) the oxide state of the particulates affected cell viability, implying that uranium’s different oxidation states contribute to different toxicological responses, and 2) each cell model reacts differently when exposed to uranium oxides, which may provide insights into the mechanistic processes associated with the exposure of radiological particulates on different biological systems. For instance, increased uranium enrichment corresponds to increased toxicity for the primary cells, but not for the immortalized cells. Our study shows that a holistic approach that incorporates similarities between model systems and types of radionuclides is required to truly develop empirical solutions for radiation exposure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA levels for regulators of the kallikrein–kinin (C1-inhibitor), coagulation (thrombomodulin, endothelial protein C receptor), and fibrinolytic (urokinase and urokinase receptor) pathways were significantly reduced in COVID-19 patients. While transcripts for several coagulation proteins were increased, those encoding tissue factor, the protein that initiates coagulation and whose expression is frequently increased in inflammatory disorders, were not increased in BALF from COVID-19 patients. Our analysis implicates enhanced propagation of coagulation and decreased fibrinolysis as drivers of the coagulopathy in the lungs of COVID-19 patients.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1972

Effect of stratified inequality of blood flow on gas exchange in liquid-filled lungs.

This investigation set out to answer two questions: (1) are the distal alveoli in the terminal lung units less well perfused than the proximal alveoli, i.e., is there stratification of blood flow; and (2) if so, does this enhance gas exchange in the presence of stratified inequality of ventilation. Excised dog lungs were ventilated with saline and perfused with blood. Following single inspirations of xenon 133 in saline and various periods of breath holding, the expired xenon concentration against volume was measured and it confirmed marked stratified inequality of ventilation under these conditions. By measuring the rate of depletion of xenon from alveoli during a period of blood flow, we showed that the alveoli which emptied at the end of expiration had 16% less blood flow than those exhaling earlier. However, by measuring the xenon concentration in pulmonary venous blood, we found that about 10% less tracer was transferred from the alveoli into the blood when the inspired xenon was stratified within the respiratory zone. Thus while stratification of blood flow was confirmed, it was shown to impair rather than enhance the efficiency of gas transfer.

West, J. B.↗
NASA NTRS1972

Finite element displacement analysis of a lung.

A method is given based on the technique of finite elements which determines theoretically the mechanical behavior of a lung-shaped body loaded by its own weight. The results of this theoretical analysis have been compared with actual measurements of alveolar size and pleural pressures in animal lungs.

Matthews, F. L.↗
NASA NTRS1986

Effect of prolonged bed rest on lung volume in normal individuals

The effect of prolonged bed rest on the lung function was studied by measuring forced vital capacity (FVC) and total lung capacity (TLC) in normal subjects before, during, and after 11- to 12-day rest periods. It was found that both FVC and TLC increased during bed rest (compared with the ambulatory controls), while residual volume and functional residual capacity of the respiratory system did not change. It is concluded that the increase in TLC by prolonged bed rest is not dependent on alterations in plasma volume.

Beckett, W. S.↗
NASA NTRS1991

Heart-Lung Interactions in Aerospace Medicine

Few of the heart-lung interactions that are discussed have been studied in any detail in the aerospace environment, but is seems that many such interactions must occur in the setting of altered accelerative loadings and pressure breathing. That few investigations are in progress suggests that clinical and academic laboratory investigators and aerospace organizations are further apart than during the pioneering work on pressure breathing and acceleration tolerance in the 1940s. The purpose is to reintroduce some of the perennial problems of aviation physiology as well as some newer aerospace concerns that may be of interest. Many possible heart-lung interactions are pondered, by necessity often drawing on data from within the aviation field, collected before the modern understanding of these interactions developed, or on recent laboratory data that may not be strictly applicable. In the field of zero-gravity effects, speculation inevitably outruns the sparse available data.

Guy, Harold J. B.↗
NASA NTRS2002

Exploring Heart and Lung Function in Space: ARMS Experiments

The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long-term bed rest.

Andre Kuipers↗
NASA NTRS2003

MRI of the lung gas-space at very low-field using hyperpolarized noble gases

In hyperpolarized (HP) noble-gas magnetic resonance imaging, large nuclear spin polarizations, about 100,000 times that ordinarily obtainable at thermal equilibrium, are created in 3He and 129Xe. The enhanced signal that results can be employed in high-resolution MRI studies of void spaces such as in the lungs. In HP gas MRI the signal-to-noise ratio (SNR) depends only weakly on the static magnetic field (B(0)), making very low-field (VLF) MRI possible; indeed, it is possible to contemplate portable MRI using light-weight solenoids or permanent magnets. This article reports the first in vivo VLF MR images of the lungs in humans and in rats, obtained at a field of only 15 millitesla (150 Gauss).

NASA Discipline Life Sciences Technologies↗
NASA NTRS2000

Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

Non-NASA Center↗