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At least 469 records · Page 26

Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

Cucinotta, Francis A.↗

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.↗

Biomedical support of man in space

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.

NASA Discipline Cardiopulmonary↗

Fatigue-test acceleration with flight-by-flight loading and heating to simulate supersonic-transport operation

Possibilities for reducing fatigue-test time for supersonic-transport materials and structures were studied in tests with simulated flight-by-flight loading. In order to determine whether short-time tests were feasible, the results of accelerated tests (2 sec per flight) were compared with the results of real-time tests (96 min per flight). The effects of design mean stress, the stress range for ground-air-ground cycles, simulated thermal stress, the number of stress cycles in each flight, and salt corrosion were studied. The flight-by-flight stress sequences were applied to notched sheet specimens of Ti-8Al-1Mo-1V and Ti-6Al-4V titanium alloys. A linear cumulative-damage analysis accounted for large changes in stress range of the simulated flights but did not account for the differences between real-time and accelerated tests. The fatigue lives from accelerated tests were generally within a factor of two of the lives from real-time tests; thus, within the scope of the investigation, accelerated testing seems feasible.

Imig, L. A.↗

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.↗

On the roles of welding residual stresses in determination of fracture toughness in austenitic stainless steel SUS 304 pipeline girth welds

Welding residual stresses especially the high tensile stresses are proved to have negative impacts on the fatigue and fracture behaviors of welded structures. In this study, a virtual fabrication of test specimens from welding process to specimen preparation was carried out by numerical simulation. An austenitic stainless steel multi-pass pipe welding was simulated by transient thermal–mechanical finite element analysis, the residual stresses were then mapped into the test specimen to evaluate fracture toughness. The findings in this study confirmed that, residual stress can be high in a sub-sized compact tensile specimen, which may accelerate or hinder the crack propagation during actual fatigue and fracture tests as reported in recent years. The influence of the cutting location and orientation of the specimen on fracture performance was investigated systematically to provide a fundamental understanding of welding residual stress and necessary insights into the specimen preparation procedure. Considering the limitation of measuring techniques and the complexity of the stress distribution, the developed numerical model can be a very useful tool to elucidate the stress evolution and quantify the effect of remaining welding stress on fracture toughness.

Fracture behavior↗

Angular velocity and acceleration meter

Meter uses a liquid crystalline film which changes coloration due to shear-stresses produced by a rotating disk. Device is advantageous in that it is not subject to bearing failure or electrical burnouts as are conventional devices.

Melamed, L.↗

Accelerated Testing Methodology for the Determination of Slow Crack Growth of Advanced Ceramics

Constant stress-rate (dynamic fatigue) testing has been used for several decades to characterize slow crack growth behavior of glass and ceramics at both ambient and elevated temperatures. The advantage of constant stress-rate testing over other methods lies in its simplicity: Strengths are measured in a routine manner at four or more stress rates by applying a constant crosshead speed or constant loading rate. The slow crack growth parameters (n and A) required for design can be estimated from a relationship between strength and stress rate. With the proper use of preloading in constant stress-rate testing, an appreciable saving of test time can be achieved. If a preload corresponding to 50 % of the strength is applied to the specimen prior to testing, 50 % of the test time can be saved as long as the strength remains unchanged regardless of the applied preload. In fact, it has been a common, empirical practice in strength testing of ceramics or optical fibers to apply some preloading (less then 40%). The purpose of this work is to study the effect of preloading on the strength to lay a theoretical foundation on such an empirical practice. For this purpose, analytical and numerical solutions of strength as a function of preloading were developed. To verify the solution, constant stress-rate testing using glass and alumina at room temperature and alumina silicon nitride, and silicon carbide at elevated temperatures was conducted in a range of preloadings from O to 90 %.

Choi, Sung R.↗

Accelerated Testing Methodology Developed for Determining the Slow Crack Growth of Advanced Ceramics

Constant stress-rate ("dynamic fatigue") testing has been used for several decades to characterize the slow crack growth behavior of glass and structural ceramics at both ambient and elevated temperatures. The advantage of such testing over other methods lies in its simplicity: strengths are measured in a routine manner at four or more stress rates by applying a constant displacement or loading rate. The slow crack growth parameters required for component design can be estimated from a relationship between strength and stress rate. With the proper use of preloading in constant stress-rate testing, test time can be reduced appreciably. If a preload corresponding to 50 percent of the strength is applied to the specimen prior to testing, 50 percent of the test time can be saved as long as the applied preload does not change the strength. In fact, it has been a common, empirical practice in the strength testing of ceramics or optical fibers to apply some preloading (<40 percent). The purpose of this work at the NASA Lewis Research Center is to study the effect of preloading on measured strength in order to add a theoretical foundation to the empirical practice.

Choi, Sung R.↗

A Simplistic Look at Limit Stresses from Random Loading

Utilizing a continuous beam model, this report compares the potential stresses imposed on the beam from a random environment with those resulting from a typical static load analysis or test simulation. The Miles' equation used to develop peak response accelerations is shown to become a force equation in the hands of strength assessment personnel. This may prove to be unrealistic since hardware dynamic stresses are related to deflection rather than load. Correlation of the stress state for any static analysis or test with the actual dynamic response stress is strictly dependent upon how well the static deflections simulate the predominant dynamic mode shape. The report proposes that the general shape of this predominant mode, along with the peak response accelerations of major masses be used in strength assessments. From these data, a tailored enforced displacement loading may prove to be more effective in reproducing random induced stresses on flight hardware.

Lee, H. M.↗

Experimental Investigation of the Effects of Acceleration on Heat Transfer in the Turbulent Boundary Layer

The objective of this research was to experimentally investigate the combined effects of freestream acceleration and surface roughness on heat transfer and fluid flow in the turbulent boundary layer. The experiments included a variety of flow conditions ranging from aerodynamically smooth to transitionally rough to fully rough boundary layers with accelerations ranging from moderate to moderately strong. The test surfaces used were a smooth-wall test surface and two rough-wall surfaces which were roughened with 1.27 mm diameter hemispheres spaced 2 and 4 base diameters apart in a staggered array. The measurements consisted of Stanton number distributions, mean temperature profiles, skin friction distributions, mean velocity profiles, turbulence intensity profiles, and Reynolds stress profiles. The Stanton numbers for the rough-wall experiments increased with acceleration. For aerodynamically smooth and transitionally rough boundary layers, the effect of roughness is not seen immediately at the beginning of the accelerated region as it is for fully rough boundary layers; however, as the boundery layer thins under acceleration, the surface becomes relatively rougher resulting in a sharp increase in Stanton number.

Chakroun, Walid M.↗

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.↗

Turbulent burst control through phase-locked traveling surface depressions

The influence of a traveling, surface depression on turbulent pre-burst flow has been investigated both theoretically and experimentally. Two-dimensional calculations of a transverse vortex (representing a 'typical' eddy) embedded in a laminar boundary layer show that properly phased-wall motion can reduce vorticity and raise wall pressure beneath the convecting vortex. Experiments in low-speed air with an electromagnetically driven wall membrane show that a traveling wall depression can accelerate flow near the wall and reduce pre-burst Reynolds stress.

Wilkinson, S. P.↗

A Transversely Isotropic Thermoelastic Theory

A continuum theory is presented for representing the thermoelastic behavior of composites that can be idealized as transversely isotropic. This theory is consistent with anisotropic viscoplastic theories being developed presently at NASA Lewis Research Center. A multiaxial statement of the theory is presented, as well as plane stress and plane strain reductions. Experimental determination of the required material parameters and their theoretical constraints are discussed. Simple homogeneously stressed elements are examined to illustrate the effect of fiber orientation on the resulting strain distribution. Finally, the multiaxial stress-strain relations are expressed in matrix form to simplify and accelerate implementation of the theory into structural analysis codes.

Arnold, S. M.↗

Aerodynamically forced vibration analysis of turbomachines

An account is given of theoretical considerations for the determination of turbomachine response under aerodynamic excitation, as in the cases of advanced turboprop rotors with highly swept blades and axial flow compressors. Dynamic response is characterized in terms of the normal modal coordinates of tuned rotating cyclic structures for both rigid and flexible hubs/disks. Implementation of the scheme is in NASTRAN; coriolis and centripetal accelerations are included, together with differential stiffness effects. Analytically predicted vibratory stresses for the blades of two different advanced turboprops are compared to those determined by wind tunnel tests conducted by NASA-Lewis.

Elchuri, V.↗

Generalized seismic analysis

There is a constant need to be able to solve for enforced motion of structures. Spacecraft need to be qualified for acceleration inputs. Truck cargoes need to be safeguarded from road mishaps. Office buildings need to withstand earthquake shocks. Marine machinery needs to be able to withstand hull shocks. All of these kinds of enforced motions are being grouped together under the heading of seismic inputs. Attempts have been made to cope with this problem over the years and they usually have ended up with some limiting or compromise conditions. The crudest approach was to limit the problem to acceleration occurring only at a base of a structure, constrained to be rigid. The analyst would assign arbitrarily outsized masses to base points. He would then calculate the magnitude of force to apply to the base mass (or masses) in order to produce the specified acceleration. He would of necessity have to sacrifice the determination of stresses in the vicinity of the base, because of the artificial nature of the input forces. The author followed the lead of John M. Biggs by using relative coordinates for a rigid base in a 1975 paper, and again in a 1981 paper . This method of relative coordinates was extended and made operational as DMAP ALTER packets to rigid formats 9, 10, 11, and 12 under contract N60921-82-C-0128. This method was presented at the twelfth NASTRAN Colloquium. Another analyst in the field developed a method that computed the forces from enforced motion then applied them as a forcing to the remaining unknowns after the knowns were partitioned off. The method was translated into DMAP ALTER's but was never made operational. All of this activity jelled into the current effort. Much thought was invested in working out ways to unshakle the analysis of enforced motions from the limitations that persisted.

Butler, Thomas G.↗

Advanced integrated life support system update

The Advanced Integrated Life Support System Program (AILSS) is an advanced development effort to integrate the life support and protection requirements using the U.S. Navy's fighter/attack mission as a starting point. The goal of AILSS is to optimally mate protection from altitude, acceleration, chemical/biological agent, thermal environment (hot, cold, and cold water immersion) stress as well as mission enhancement through improved restraint, night vision, and head-mounted reticules and displays to ensure mission capability. The primary emphasis to date has been to establish garment design requirements and tradeoffs for protection. Here the garment and the human interface are treated as a system. Twelve state-off-the-art concepts from government and industry were evaluated for design versus performance. On the basis of a combination of centrifuge, thermal manikin data, thermal modeling, and mobility studies, some key design parameters have been determined. Future efforts will concentrate on the integration of protection through garment design and the use of a single layer, multiple function concept to streamline the garment system.

Whitley, Phillip E.↗