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All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Peripheral Microvascular Responses to Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure Stresses in Humans

The response of the cutaneous microcirculation to orthostatic stress varies along the length of the body due to the interaction of central controls with regional responses to local blood pressure. We hypothesize that artificial orthostatic stresses such as Gz centrifugation and LBNP differ from whole-body tilting in terms of the distribution of microvascular blood flow. Cutaneous microvascular flows were measured by laser Doppler flowmetry at the neck, thigh, and leg of 15 normal subjects. Volunteers underwent stepwise head-up tilt (HUT) and short- and long-arm centrifugation protocols from supine control (0 Gz) to 0.2, 0.4, 0.6, 0.8, 1.0, 0.8, 0.6, 0.4, 0.2, and 0 Gz at the feet, for 30-s periods with 10-s transitions between levels. The same subjects underwent a corresponding supine LBNP protocol, up to 100 mmHg (in 20 mmHg increments) and back to zero pressure, which produced transmural pressure across blood vessels in the foot approximately equal to the HUT protocol. In general, application of all orthostatic stresses produced significant flow reductions in the lower body (p less than 0.05) and inconsistent changes in the neck. At low levels of each stress (0.4 Gz, 40 mmHg), LBNP generated the greatest relative reduction in flow in the lower body (-66.9+/-5.7%, thigh; -60.6 +/-5.7%, leg, mean +/- SE). HUT caused a less severe flow reduction than LBNP at the thigh and leg (-39.9 +/- 8.1% and -55.9+/-4.8%), while the effects induced by both forms of centrifugation were the least profound. Higher levels of each stress generally resulted in similar responses. These responses exhibit a consistent relationship to hypothesized changes in local microvascular transmural pressure, suggesting that myogenic and veno-arteriolar reflexes play a significant role in determining microvascular perfusion during orthostatic stress.

Breit, G. A.↗
NASA NTRS2001

Constituent Effects on the Stress-Strain Behavior of Woven Melt-Infiltrated SiC Composites

The stress-strain behavior of 2D woven SiC fiber reinforced, melt-infiltrated SiC matrix composites with BN interphases were studied for composites fabricated with different fiber tow ends per unit length, different composite thickness, and different numbers of plies. In general, the stress-strain behavior, i.e., the 'knee' in the curve and the final slope of the stress-strain curve, was controlled by the volume fraction of fibers. Some of the composites exhibited debonding and sliding in between the interphase and the matrix rather than the more common debonding and sliding interface between the fiber and the interphase. Composites that exhibited this 'outside debonding' interface, in general, had lower elastic moduli and higher ultimate strains as well as longer pull-out lengths compared to the 'inside debonding' interface composites. Stress-strain curves were modeled where matrix crack formation as a function of stress was approximated from the acoustic emission activity and the measured crack density from the failed specimens. Interfacial shear strength measurements from individual fiber push-in tests were in good agreement with the interfacial shear strength values used to model the stress-strain curves.

Morscher, Gregory N.↗
NASA NTRS2002

Hydrostatic Stress Effect On the Yield Behavior of Inconel 100

Classical metal plasticity theory assumes that hydrostatic stress has no effect on the yield and postyield behavior of metals. Recent reexaminations of classical theory have revealed a significant effect of hydrostatic stress on the yield behavior of notched geometries. New experiments and nonlinear finite element analyses (FEA) of Inconel 100 (IN 100) equal-arm bend and double-edge notch tension (DENT) test specimens have revealed the effect of internal hydrostatic tensile stresses on yielding. Nonlinear FEA using the von Mises (yielding is independent of hydrostatic stress) and the Drucker-Prager (yielding is linearly dependent on hydrostatic stress) yield functions was performed. In all test cases, the von Mises constitutive model, which is independent of hydrostatic pressure, overestimated the load for a given displacement or strain. Considering the failure displacements or strains, the Drucker-Prager FEMs predicted loads that were 3% to 5% lower than the von Mises values. For the failure loads, the Drucker Prager FEMs predicted strains that were 20% to 35% greater than the von Mises values. The Drucker-Prager yield function seems to more accurately predict the overall specimen response of geometries with significant internal hydrostatic stress influence.

Allen, Phillip A.↗
NASA NTRS2003

Satellite Detection of the Convection Generated Stresses in Earth

We review research developments on satellite detection of the convection generated stresses in the Earth for seismic hazard assessment and Earth resource survey. Particular emphasis is laid upon recent progress and results of stress calculations from which the origin and evolution of the tectonic features on Earth's surface can be scientifically addressed. An important aspect of the recent research development in tectonic stresses relative to earthquakes is the implications for earthquake forecasting and prediction. We have demonstrated that earthquakes occur on the ring of fire around the Pacific in response to the tectonic stresses induced by mantle convection. We propose a systematic global assessment of the seismic hazard based on variations of tectonic stresses in the Earth as observed by satellites. This space geodynamic approach for assessing the seismic hazard is unique in that it can pinpoint the triggering stresses for large earthquakes without ambiguities of geological structures, fault geometries, and other tectonic properties. Also, it is distinct from the probabilistic seismic hazard assessment models in the literature, which are based only on extrapolations of available earthquake data.

Liu, Han-Shou↗
NASA NTRS2004

Subsurface Stress Fields In Single Crystal (Anisotropic) Contacts

Single crystal superalloy turbine blades used in high pressure turbomachinery are subject to conditions of high temperature, triaxial steady and alternating stresses, fretting stresses in the blade attachment and damper contact locations, and exposure to high-pressure hydrogen. The blades are also subjected to extreme variations in temperature during start-up and shutdown transients. The most prevalent HCF failure modes observed in these blades during operation include crystallographic crack initiation/propagation on octahedral planes, and noncrystallographic initiation with crystallographic growth. Numerous cases of crack initiation and crack propagation at the blade leading edge tip, blade attachment regions, and damper contact locations have been documented. Understanding crack initiation/propagation under mixed-mode loading conditions is critical for establishing a systematic procedure for evaluating HCF life of single crystal turbine blades. This paper presents analytical and numerical techniques for evaluating two and three dimensional subsurface stress fields in anisotropic contacts. The subsurface stress results are required for evaluating contact fatigue life at damper contacts and dovetail attachment regions in single crystal nickel-base superalloy turbine blades. An analytical procedure is , presented, for evaluating the subsurface stresses in the elastic half-space, using a complex potential method outlined by Lekhnitskii. Numerical results are presented for cylindrical and spherical anisotropic contacts, using finite element analysis. Effects of crystal orientation on stress response and fatigue life are examined.

Arakere, Nagaraj K.↗
NASA NTRS2002

Properties of the Residual Stress of the Temporally Filtered Navier-Stokes Equations

The development of a unifying framework among direct numerical simulations, large-eddy simulations, and statistically averaged formulations of the Navier-Stokes equations, is of current interest. Toward that goal, the properties of the residual (subgrid-scale) stress of the temporally filtered Navier-Stokes equations are carefully examined. Causal time-domain filters, parameterized by a temporal filter width 0 less than Delta less than infinity, are considered. For several reasons, the differential forms of such filters are preferred to their corresponding integral forms; among these, storage requirements for differential forms are typically much less than for integral forms and, for some filters, are independent of Delta. The behavior of the residual stress in the limits of both vanishing and in infinite filter widths is examined. It is shown analytically that, in the limit Delta to 0, the residual stress vanishes, in which case the Navier-Stokes equations are recovered from the temporally filtered equations. Alternately, in the limit Delta to infinity, the residual stress is equivalent to the long-time averaged stress, and the Reynolds-averaged Navier-Stokes equations are recovered from the temporally filtered equations. The predicted behavior at the asymptotic limits of filter width is further validated by numerical simulations of the temporally filtered forced, viscous Burger's equation. Finally, finite filter widths are also considered, and a priori analyses of temporal similarity and temporal approximate deconvolution models of the residual stress are conducted.

Pruett, C. D.↗
NASA NTRS2002

Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography

BACKGROUND: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall-motion analysis. Interpretation of dobutamine stress echocardiography is observer-dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. METHODS AND RESULTS: Twenty-nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5-3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. CONCLUSION: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.

Non-NASA Center↗
NASA NTRS1991

Soluble carbohydrate allocation to roots, photosynthetic rate of leaves, and nitrate assimilation as affected by nitrogen stress and irradiance

Upon resupply of exogenous nitrogen to nitrogen-stressed plants, uptake rate of nitrogen is enhanced relative to nonstressed plants. Absorption of nitrogen presumably is dependent on availability of carbohydrates in the roots. A buildup in soluble carbohydrates thus should occur in roots of nitrogen-stressed plants, and upon resupply of exogenous nitrogen the increased uptake rate should be accompanied by a rapid decline in carbohydrates to prestress levels. To evaluate this relationship, three sets of tobacco plants growing in a complete hydroponic solution containing 1.0 mM NO3- were either continued in the complete solution for 21 d, transferred to a minus-nitrogen solution for 21 d, or transferred to a minus-nitrogen solution for 8-9 d and then returned to the 1.0 mM NO3- solution. These nitrogen treatments were imposed upon plants growing at photosynthetic photon flux densities of 700 and 350 micromoles m-2 s-1. Soluble carbohydrate levels in roots increased during onset of nitrogen stress to levels that were fourfold greater than in roots of non-stressed plants. Following resupply of external nitrogen, a rapid resumption of nitrogen uptake was accompanied by a decline in soluble carbohydrates in roots to levels characteristic of nonstressed plants. This pattern of soluble carbohydrate levels in roots during onset of and recovery from nitrogen stress occurred at both irradiance levels. The response of net photosynthetic rate to nitrogen stress could be expressed as a nonlinear function of concentration of reduced nitrogen in leaves. The net photosynthetic rate at a given concentration of reduced nitrogen, however, averaged 10% less at the lower than at the higher irradiance. The decline in net photosynthetic rate per unit of reduced nitrogen in leaves at the lower irradiance was accompanied by an increase in the nitrate fraction of total nitrogen in leaves from 20% at the higher irradiance to 38% at the lower irradiance.

NASA Discipline Number 61-10↗
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↗
NASA NTRS2004

Creep and Stress-strain Behavior After Creep from Sic Fiber Reinforced, Melt-infiltrated Sic Matrix Composites

Silicon carbide fiber (Hi-Nicalon Type S, Nippon Carbon) reinforced silicon carbide matrix composites containing melt-infiltrated Si were subjected to creep at 1315 C for a number of different stress conditions, This study is aimed at understanding the time-dependent creep behavior of CMCs for desired use-conditions, and also more importantly, how the stress-strain response changes as a result of the time-temperature-stress history of the crept material. For the specimens that did not rupture, fast fracture experiments were performed at 1315 C or at room temperature immediately following tensile creep. In many cases, the stress-strain response and the resulting matrix cracking stress of the composite change due to stress-redistribution between composite constituents during tensile creep. The paper will discuss these results and its implications on applications of these materials for turbine engine components.

Morscher, Gregory N.↗
NASA NTRS2005

Stress Analysis of B-52B and B-52H Air-Launching Systems Failure-Critical Structural Components

The operational life analysis of any airborne failure-critical structural component requires the stress-load equation, which relates the applied load to the maximum tangential tensile stress at the critical stress point. The failure-critical structural components identified are the B-52B Pegasus pylon adapter shackles, B-52B Pegasus pylon hooks, B-52H airplane pylon hooks, B-52H airplane front fittings, B-52H airplane rear pylon fitting, and the B-52H airplane pylon lower sway brace. Finite-element stress analysis was performed on the said structural components, and the critical stress point was located and the stress-load equation was established for each failure-critical structural component. The ultimate load, yield load, and proof load needed for operational life analysis were established for each failure-critical structural component.

Ko, William L.↗
NASA NTRS2009

Analytical Predictions of Thermal Stress in the Stardust PICA Heatshield Under Reentry Flight Conditions

We performed finite element analyses on a model of the Phenolic Impregnated Carbon Ablator (PICA) heatshield from the Stardust sample return capsule (SRC) to predict the thermal stresses in the PICA material during reentry. The heatshield on the Stardust SRC was a 0.83 m sphere cone, fabricated from a single piece of 5.82 cm-thick PICA. The heatshield performed successfully during Earth reentry of the SRC in January 2006. Material response analyses of the full, axisymmetric PICA heatshield were run using the Two-Dimensional Implicit Ablation, Pyrolysis, and Thermal Response Program (TITAN). Peak surface temperatures were predicted to be 3385K, while the temperature at the PICA backface remained at the estimated initial cold-soak temperature of 278K. Surface recession and temperature distribution results from TITAN, at several points in the reentry trajectory, were mapped onto an axisymmetric finite element model of the heatshield. We used the finite element model to predict the thermal stresses in the PICA from differential thermal expansion. The predicted peak compressive stress in the PICA heatshield was 1.38 MPa. Although this level of stress exceeded the chosen design limit for compressive stresses in PICA tiles for the design of the Orion crew exploration vehicle heatshield, the Stardust heatshield exhibited no obvious mechanical failures from thermal stress. The analyses of the Stardust heatshield were used to assess and adjust the level of conservatism in the finite element analyses in support of the Orion heatshield design.

Squire, Thomas↗
NASA NTRS2010

Composite Overwrapped Pressure Vessels (COPV) Stress Rupture Test: Part 2

One of the major concerns for the aging Space Shuttle fleet is the stress rupture life of composite overwrapped pressure vessels (COPVs). Stress rupture life of a COPY has been defined as the minimum time during which the composite maintains structural integrity considering the combined effects of stress levels and time. To assist in the evaluation of the aging COPVs in the Orbiter fleet an analytical reliability model was developed. The actual data used to construct this model was from testing of COPVs constructed of similar, but not exactly same materials and pressure cycles as used on Orbiter vessels. Since no actual Orbiter COPV stress rupture data exists the Space Shuttle Program decided to run a stress rupture test to compare to model predictions. Due to availability of spares, the testing was unfortunately limited to one 40" vessel. The stress rupture test was performed at maximum operating pressure at an elevated temperature to accelerate aging. The test was performed in two phases. The first phase, 130 F, a moderately accelerated test designed to achieve the midpoint of the model predicted point reliability. A more aggressive second phase, performed at 160 F, was designed to determine if the test article will exceed the 95% confidence interval ofthe model. In phase 3, the vessel pressure was increased to above maximum operating pressure while maintaining the phase 2 temperature. After reaching enough effectives hours to reach the 99.99% confidence level of the model phase 4 testing began when the temperature was increased to greater than 170 F. The vessel was maintained at phase 4 conditions until it failed after over 3 million effect hours. This paper will discuss the results of this test, it's implications and possible follow-on testing.

Russell, Richard↗
NASA NTRS2009

Composite Overwrapped Pressure Vessels (COPV) Stress Rupture Test

One of the major concerns for the aging Space Shuttle fleet is the stress rupture life of composite overwrapped pressure vessels (COPVs). Stress rupture life of a COPV has been defined as the minimum time during which the composite maintains structural integrity considering the combined effects of stress levels and time. To assist in the evaluation of the aging COPVs in the Orbiter fleet an analytical reliability model was developed. The actual data used to construct this model was from testing of COPVs constructed of similar, but not exactly same materials and pressure cycles as used on Orbiter vessels. Since no actual Orbiter COPV stress rupture data exists the Space Shuttle Program decided to run a stress rupture test to compare to model predictions. Due to availability of spares, the testing was unfortunately limited to one 40" vessel. The stress rupture test was performed at maximum operating pressure at an elevated temperature to accelerate aging. The test was performed in two phases. The first phase, 130 F, a moderately accelerated test designed to achieve the midpoint of the model predicted point reliability. The more aggressive second phase, performed at 160 F was designed to determine if the test article will exceed the 95% confidence interval of the model. This paper will discuss the results of this test, it's implications and possible follow-on testing.

Russell, Richard↗
NASA NTRS2011

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Lee, Stuart M. C.↗
NASA NTRS2014

Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts during and after Long-duration Spaceflight

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and investigate if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight, and structural and functional measures for up to 5 years after landing. METHODS We will study 12 astronauts before, during, and up to 5 years after long-duration ISS missions. A panel of biomarkers of oxidative and inflammatory stress will be measured twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the postflight recovery phase (approx 3 days after landing). Arterial structure and vascular compliance will be measured at the same times and also at 1, 3, and 5 years after landing (surveillance). Arterial function will be measured using the same preflight, postflight, and surveillance schedule as arterial structure and vascular compliance measures, but will not be measured inflight. Biomarkers, some of which we have previously shown to be elevated with spaceflight, will be measured in venous blood samples and 24-h (in-flight) and 48-h (pre- and post-flight) urine pools. Arterial structure will be assessed from measures of carotid intima-media thickness, which have been shown to be better indicators of atherosclerotic than the Framingham Risk Score. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and is a sensitive predictor of atherosclerotic risk. Arterial pulse pressure measured in the brachial artery and stroke volume measured from cardiac ultrasound will be used to assess hemodynamic status, cardiac function, and systemic vascular compliance. Three astronauts are actively participating in the preflight data collection and training activities. One astronaut has completed all preflight activities and will participate in the first in-flight data collection sessions by the end of 2013. The first post-flight data collection sessions will occur in the spring of 2014. EXPECTED RESULTS We hypothesize that biomarkers of oxidative and inflammatory stress will increased with spaceflight and will correlate with increased carotid intima-media thickness during and after flight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but biomarkers of inflammatory stress and vascular indices of atherosclerotic risk will remain elevated.

Lee, Stuart M. C.↗
NASA NTRS2016

A Piezoelectric Shear Stress Sensor

In this paper, a piezoelectric sensor with a floating element was developed for shear stress measurement. The piezoelectric sensor was designed to detect the pure shear stress suppressing effects of normal stress generated from the vortex lift-up by applying opposite poling vectors to the: piezoelectric elements. The sensor was first calibrated in the lab by applying shear forces and it showed high sensitivity to shear stress (=91.3 +/- 2.1 pC/Pa) due to the high piezoelectric coefficients of PMN-33%PT (d31=-1330 pC/N). The sensor also showed almost no sensitivity to normal stress (less than 1.2 pC/Pa) because of the electromechanical symmetry of the device. The usable frequency range of the sensor is 0-800 Hz. Keywords: Piezoelectric sensor, shear stress, floating element, electromechanical symmetry

Kim, Taeyang↗
NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗