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At least 343 records · Page 19

A MULTI TARGETED DIETARY SUPPLEMENT AS A POTENTIAL COUNTERMEASURE FOR DEEP SPACE EXPLORATION

Future deep space exploration to the Moon and Mars and beyond are currently major goals of NASA. Space flight presents unique challenges to the human physiology from the combined effects of microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

Stephanie Puukila↗

Predicted star counts in selected fields and photometric bands Applications to galactic structure, the disk luminosity function, and the detection of a massive halo

Tables are presented of predicted star counts in 17 selected directions on the sky as a function of apparent B, V, R, and I magnitudes and absolute visual magnitudes calculated from the Bahcall-Soneira Galaxy model. It is noted that eight of the fields were selected ab initio for their usefulness in determining from star counts either parameters of galactic structure, the faint end of the disk luminosity function, or the detection of a massive stellar halo. Star counts in specified fields to m sub I = 19 mag are able to reveal the faint end of the disk luminosity function down to the end of the hydrogen-burning main sequence. It is thought that star counts at high galactic latitudes to m sub I = 22 mag should reveal the stellar constituents of a massive halo if they are massive enough to be on the hydrogen-burning main sequence.

Bahcall, J. N.↗

Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

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.↗

The structure of Airy's stress function in multiply connected regions

In solving two-dimensional problems using Airy's stress function for multiply connected regions, the form of the function depends on the dislocations and boundary forces present. The structure of Airy's function is shown to consist of a part expressible in terms of boundary forces and a part expressible in the manner of Poincare. Meanings of the constants occurring in Poincare's expression are discussed.

FRAMES, GRIDWORKS AND TRUSSES↗

Oblique hypervelocity impact response of dual-sheet structures

The results of a continuing investigation of the phenomena associated with the oblique hypervelocity impact of spherical projectiles onto multi-sheet aluminum structures are given. A series of equations that quantitatively describes these phenomena is obtained through a regression of experimental data. These equations characterize observed ricochet and penetration damage phenomena in a multi-sheet structure as functions of geometric parameters of the structure and the diameter, obliquity, and velocity of the impacting projectile. Crater damage observed on the ricochet witness plates is used to determine the sizes and speeds of the ricochet debris particles that caused the damage. It is observed that the diameter of the most damaging ricochet debris particle can be as large as 40 percent of the original particle diameter and can travel at speeds between 24 percent and 36 percent of the original projectile impact velocity. The equations necessary for the design of shielding panels that will protect external systems from such ricochet debris damage are also developed. The dimensions of these shielding panels are shown to be strongly dependent on their inclination and on their circumferential distribution around the spacecraft.

Schonberg, William P.↗

If walls could talk

The plant cell wall is very complex, both in structure and function. The wall components and the mechanical properties of the wall have been implicated in conveying information that is important for morphogenesis. Proteoglycans, fragments of polysaccharides and the structural integrity of the wall may relay signals that influence cellular differentiation and growth control. Furthering our knowledge of cell wall structure and function is likely to have a profound impact on our understanding of how plant cells communicate with the extracellular environment.

Review↗

The evolution of concepts of vestibular peripheral information processing: toward the dynamic, adaptive, parallel processing macular model

In a letter to Robert Hooke, written on 5 February, 1675, Isaac Newton wrote "If I have seen further than certain other men it is by standing upon the shoulders of giants." In his context, Newton was referring to the work of Galileo and Kepler, who preceded him. However, every field has its own giants, those men and women who went before us and, often with few tools at their disposal, uncovered the facts that enabled later researchers to advance knowledge in a particular area. This review traces the history of the evolution of views from early giants in the field of vestibular research to modern concepts of vestibular organ organization and function. Emphasis will be placed on the mammalian maculae as peripheral processors of linear accelerations acting on the head. This review shows that early, correct findings were sometimes unfortunately disregarded, impeding later investigations into the structure and function of the vestibular organs. The central themes are that the macular organs are highly complex, dynamic, adaptive, distributed parallel processors of information, and that historical references can help us to understand our own place in advancing knowledge about their complicated structure and functions.

Review, Tutorial↗

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Platts, Steven H.↗

Musculoskeletal discipline science plan

Life sciences research in the musculoskeletal discipline must identify possible consequences of weightlessness on this system, understand the mechanisms of these effects, and develop effective and operationally practical countermeasures to protect crewmembers. The musculoskeletal system is highly plastic in that is possesses the inherent capability to adapt its structural and functional properties in accordance with the type and degree of stimuli imposed on it. Prolonged space travel is essentially a period of significant unloading of the musculoskeletal system. This results in adaptive responses in the structure and function of this system, placing it on the low end of a continuum from one of complete disuse to one of maximal use. There is a high probability that the musculoskeletal system is functionally impaired with increasing duration of weightlessness. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences division research and development activities in the area of musculoskeletal function. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines research opportunities, which encompass critical questions in the subdiscipline areas (e.g., muscle, bone, and other musculoskeletal connective tissues). These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

Source record↗

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

Westby, Christian M.↗

Comparing the effectiveness of software testing strategies

This study compares the results of code reading, functional testing, and structural testing in three aspects of software testing: fault detection effectiveness, fault detection cost, and classes of faults detected. Thirty two professional programmers and 42 advanced students applied the three techniques to four unit-sized programs in a fractional experimental design. The major results of this study are the following: (1) With the professional programmers, code reading detected more software faults and had a higher detection rate than did functional or structural testing, while functional testing detected more faults than did structural testing, but functional and structural testing were not different in fault detection rate. (2) In one advanced student subject group, code reading and functional testing were not different in faults found, but were superior to structural testing, while in the other advanced student subject group there was no difference among the techniques. (3) With the advanced student subjects, the three techniques were not different in fault deteciton rate. (4) Number of faults observed, fault detection rate, and total effort in detection depended on the type of software tested. (5) Code reading detected more interface faults than did the other methods. (6) Functional testing detected more control faults than did the other methods. (7) When asked to estimate the percentage of faults detected, code readers gave the most accurate estimates while functional testers gave the least accurate estimates. Appendix B includes the source code for the word.

Basili, Victor R.↗

Tracing structural optima as a function of available resources by a homotopy method

Optimization problems are typically solved by starting with an initial estimate and proceeding iteratively to improve it until the optimum is found. The design points along the path from the initial estimate to the optimum are usually of no value. The present work proposes a strategy for tracing a path of optimum solutions parameterized by the amount of available resources. The paper specifically treats the optimum design of a structure to maximize its buckling load. Equations for the optimum path are obtained using Lagrange multipliers, and solved by a homotopy method. The solution path has several transitions from unimodal to bimodal solutions. The Lagrange multipliers and second-order optimality conditions are used to detect branching points and to switch to the optimum solution path. The procedure is applied to the design of a foundation which supports a column for maximum buckling load. Using the total available foundation stiffness as a homotopy parameter, a set of optimum foundation designs is obtained.

Haftka, Raphael T.↗

The structure of the software cost function

It is the purpose of this paper to analyze the structure of the cost estimating relationships that commercial cost models use and to test whether they are viable cost functions.

cost function cost estimating relationship wage ra↗

The NASTRAN user's manual

All information directly associated with problem solving using the NASTRAN program is presented. This structural analysis program uses the finite element approach to structural modeling wherein the distributed finite properties of a structure are represented by a finite element of structural elements which are interconnected at a finite number of grid points, to which loads are applied and for which displacements are calculated. Procedures are described for defining and loading a structural model. Functional references for every card used for structural modeling, the NASTRAN data deck and control cards, problem solution sequences (rigid formats), using the plotting capability, writing a direct matrix abstraction program, and diagnostic messages are explained. A dictionary of mnemonics, acronyms, phrases, and other commonly used NASTRAN terms is included.

Source record↗

Further investigations of oblique hypervelocity impact phenomena

The results of a continuing investigation of the phenomena associated with the oblique hypervelocity impact of spherical projectiles onto multi-sheet aluminum structures are described. A series of equations that quantitatively describes these phenomena is obtained through a regression of experimental data. These equations characterize observed ricoshet and penetration damage phenomena in a multi-sheet structure as functions of the geometric parameters of the structure and the diameter, obliquity, and velocity of the impacting projectile. Crater damage observed on the ricochet witness plates is used to determine the sizes and speeds of the ricochet debris particles that caused the damage. It is shown that, in general, the most damaging ricochet debris particle is approximately 0.25 cm (0.10 in) in diameter and travels at the speed of approximately 2.1 km/sec (6,890 ft/sec). The equations necessary for the design of shielding panels that will protect external systems from such ricochet debris damage are also developed. The dimensions of these shielding panels are shown to be strongly dependent on their inclination and on their circumferential distribution around the spacecraft. It is concluded that obliquity effects of high-speed impacts must be considered in the design of any structure exposed to the meteoroid and space debris environment.

Schonberg, William P.↗