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At least 613 records · Page 34

Neurovascular Outcomes of Ionizing Radiation in Human Blood-Brain Barrier Models

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.15-0.5Gy 250MeV/n 4He and 0.3-0.8Gy 600MeV/n 56Fe; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗

An empirical stress-intensity factor equation for the surface crack

This paper presents an empirical stress-intensity factor equation for a surface crack as a function of parametric angle, crack depth, crack length, plate thickness and plate width for tension and bending loads. The stress-intensity factors used to develop the equation were obtained from a previous three-dimensional, finite-element analysis of semielliptical surface cracks in finite elastic plates subjected to tension or bending loads. A wide range of configuration parameters was included in the equation. The ratios of crack length to plate thickness and the ratios of crack depth to crack length ranged from 0 to 1.0. The effects of plate width on stress-intensity variations along the crack front were also included. The equation was used to predict patterns of surface-crack growth under tension or bending fatigue loads. The equation was also used to correlate surface-crack fracture data for a brittle epoxy material within + or - 10 percent for a wide range of crack shapes and crack sizes.

Newman, J. C., Jr.↗

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↗

Thermally induced stresses and deformations in angle-ply composite tubes

Cure-induced uniform temperature change effects on the stresses, axial expansion, and thermally-induced twist of four specific angle-ply tube designs are discussed with a view to the tubes' use as major space structure components. The stresses and deformations in the tubes are studied as a function of the four designs, the off-axis angle, and the single-material and hybrid reinforcing-material construction used. It is found that tube design has a minor influence on the stresses, axial stiffness, and axial thermal expansion characteristics, which are more directly a function of off-axis angle and material selection; tube design is, however, the primary influence in the definition of thermally-induced twist and torsional stiffness characteristics. None of the designs is free of thermally induced twist.

Hyer, M. W.↗

Deflections of anisotropic sandwich beams with variable face sheets and core thicknesses

A sandwich construction consists of a low-density core material with high strength face sheets bounded to the top and bottom surfaces. The construction has been widely used in the aerospace and marine industries due to its outstanding characteristics such as noise absorption, weight minimization, heat insulation, and better bending stiffness. In sandwich structures used in high-performance aircraft, the face sheets are often made of fiber-reinforced composite materials and the core is made of honeycomb. The structures may also have variable thickness so as to satisfy aerodynamic requirements. In the stress analysis, the constant-thickness face sheets are usually considered as membrane and the core is assumed to be inextensible but deformable in the thickness direction. The static behavior of variable-thickness, isotropic and homogeneous sandwich beams was successfully studied by employing a constant-thickness theory but allowing stiffnesses to vary in accordance with local thickness variations. It has been recently found in a refined theory that the analyses based on the constant thickness theory locally can lead to significant errors in structural responses if the sandwich beam is thickness-tapered and the cores are deformable in transverse shear. The errors arise mainly from two factors: (1) the transverse shear components of the membrane forces in the face sheets alter the transverse shears carried by the core; and (2) the face-sheet membrane strains arise from transverse shear deformation of the core. In practice the variable thickness may not only exist in core but also in face sheets. The thickness-variations may even be a type of step function. In this case the transverse shear stress in the face sheets and bending stress in the core should be taken into account in the refined theory mentioned. In the present study, energy principles are employed in deriving governing equations for general bending of anisotropic sandwich beams with variable thickness in both face sheets and cores. Solutions to these equations are based on a finite difference scheme. As an example in application, a simply supported thickness-tapered sandwich beam subject to a concentrated load at its center is considered. Let W' be the maximum deflection of the beam in which face sheets are considered as membrane, while W'' is that based on using the modified refined theory. It is found that W' is always larger than W'', however, the magnitude of (W'- W'') appears to be insensitive to the change of the taper of the beam.

Lu, Chu-Ho↗

Fracture and crack growth in orthotropic laminates

Solutions are developed for the two dimensional region containing unidirectional fibers with initial damage in the form of a notch, a rectangular cut out, and a circular hole. An ultimate stress failure criterion is used for both the fibers and the matrix, simple tension for the fibers, and shear failure for the matrix. Models which account for longitudinal matrix yielding and splitting as well as transverse matrix yielding and fiber breakage as a function of initial damage, material properties, and applied stress are presented. For ductile matrix composites the results indicate that longitudinal matrix yielding and transverse notch extension are the most significant forms of damage. The extent of the stable transverse damage is shown to be approximately constant, independent of initial notch length. In the case of brittle matrix composites (graphite/epoxy) longitudinal splitting is shown to be the dominant form of damage.

Goree, J. G.↗

Investigating the Effects of Temperature on the Signatures of Shocks Propagated Through Impacts into Minerals Found in Comets and Asteroids

Comets and asteroids are subjected to extremely cold conditions throughout their lifetimes. During their sojourns in the solar system, they are subjected to collisions at speeds that are easily capable of generating shock waves in their constituent materials. In addition to ices, more common silicate minerals such as olivines and pyroxenes are important components of these objects. The collision-induced shocks could affect the spectral signatures of those mineral components, which could in turn be detected telescopically. We have embarked on a project to determine how impact-generated shock might affect the reflectance spectra and structures of select silicates as both impact speed and target temperature are varied systematically. While the effects of impact speed (in the form of shock stress) on numerous materials have been and continue to be studied, the role of target temperature has received comparatively little attention, presumably because of the operational difficulties it can introduce to experimentation. Our experiments were performed with the vertical gun in the Experimental Impact Laboratory of the Johnson Space Center. A liquid-nitrogen system was plumbed to permit cooling of the target container and its contents under vacuum to temperatures as low as -100 C (173 K). Temperatures were monitored by thermocouples mounted on the outside of the target container. Because those sensors were not in contact with the target material at impact, the measured temperatures are treated as lower limits for the actual values. Peridot (Mg-rich olivine) and enstatite (Mg-rich orthopyroxene) were used as targets, which involved the impact of alumina (Al2O3) spheres at speeds of 2.0 - 2.7 km s(exp -1) and temperatures covering 25 C to -100 C (298 K to 173 K). We have begun collecting and analyzing data in the near to mid-IR with a Fourier-transform infrared spectrometer, and preliminary analyses show that notable differences in absorption-band strength and position occur as functions of both impact speed (peak shock stress) and initial temperature.

Lederer, Susan M.↗

Nonlinear viscoelastic response of highly filled elastomers under multiaxial finite deformation

A biaxial tester was used to obtain precise biaxial stress responses of highly filled, high strain capability elastomers. Stress-relaxation experiments show that the time-dependent part of the relaxation response can be reasonably approximated by a function which is strain and biaxiality independent. Thus, isochronal data from the stress-relaxation curves can be used to determine the stored energy density function. The complex behavior of the elastomers under biaxial deformation may be caused by dewetting.

Peng, Steven T. J.↗

Integrins, tensegrity, and mechanotransduction

Physical forces, such as those due to gravity, play an important role in tissue development and remodeling. Yet, little is known about how individual cells sense mechanical signals or how they transduce them into a chemical response. Rather than listing the numerous signal pathways that have been found to be sensitive to mechanical stimulation, we need to place potential molecular signaling mechanisms within the context of the entire cell. The model presented is based on the concept that cells use tensegrity architecture to organize their cytoskeleton and stabilize their form. Studies with stick and string tensegrity cell models predict that living cells are hard-wired to respond immediately to external mechanical stresses. This hard-wiring exists in the form of discrete cytoskeletal filament networks that mechanically couple specific cell surface receptors, such as integrins, to nuclear matrix scaffolds and to potential transducing molecules that physically associate with the cytoskeleton. If these signaling molecules do function in a "solid-state", then mechanical stresses may be transduced into biochemical responses through force-dependent changes in cytoskeletal geometry or through local alterations in thermodynamic or kinetic parameters. Changes in cytoskeletal tension (prestress) also may play a role in signal amplification and adaptation. Recent experimental results are described which provide direct support for the tensegrity theory.

Review↗

A stress index model for ascending balloons

Attention is given to the development on the part of NASA of a simplified stress 'index' model to establish the relative stress magnitudes along a balloon's gore position as a function of altitude. Application of this model to several hundred balloon flights showed a good correlation between balloon failure rate and stress 'index' level. This model can be used during the balloon design process to lower the levels of stress in the balloon. By increasing the wall thickness of the balloon, adding caps, lengthening caps, or using external caps, lower stress can be accomplished. As a result, in January 1985, the NASA Balloon Program established a stress index specification to limit the design and flight stresses for NASA balloons.

Smith, I. S.↗

Thermoplasticity of coupled bodies in the case of stress-dependent heat transfer

The problem of the thermal stresses in coupled deformable bodies is formulated for the case where the heat-transfer coefficient at the common boundary depends on the stress-strain state of the bodies (e.g., is a function of the normal pressure at the common boundary). Several one-dimensional problems are solved in this formulation. Among these problems is the determination of the thermal stresses in an n-layer plate and in a two-layer cylinder.

Kilikovskaya, O. A.↗

Stoichiometry of the large conductance bacterial mechanosensitive channel of E. coli. A biochemical study

MscL, a 15 kDa transmembrane protein, is the only component involved in the formation of a 3 nS channel in the inner membrane of Escherichia coli that opens in response to mechanical or osmotic stress. While previous data had suggested that the functional MscL complex might be a hexamer, a recent crystallographic study of the MscL homologue from M. tuberculosis reveals a pentameric structure. The present work further examines the stoichiometry of the E. coli MscL using a variety of biochemical approaches. Detergent-purified 6His-MscL in solution and MscL in the membrane could be chemically crosslinked with the products displaying ladderlike patterns on SDS gels. Three crosslinking agents (EDC, DMS, and DMA) used at saturating concentrations invariably generated pentamers as the largest product. DSS produced additional bands corresponding to larger complexes although the pentamer band appeared to be the predominant product at high levels of crosslinker. It is not clear whether these extra bands reflect a difference in the crosslinking chemistry of DSS or whether its spacer arm is the longest of those used, or a combination of both facts. For the detergent-solubilized 6His-MscL both sedimentation equilibrium and gel chromatography showed the presence of multiple species. Thus the longer spacer arm could permit both intra- and intercomplex linkages. Nonetheless, the patterns obtained with all agents are consistent with and strongly suggest a pentameric organization for the MscL channel. Expression of MscL as genetically engineered double or triple subunit tandems yields low numbers of functional channels as compared to expressed monomers. The double-tandem assemblies must have an even number of subunits and crosslinking in the membrane confirmed hexamerization. Gel chromatography clearly demonstrated that the channels formed from the double tandems were larger than those formed from WT MscL, consistent with the native channel being pentameric. The observation that both double and triple tandems form channels of normal conductance implies that the pentameric assembly is to some degree independent of the number of subunit repeats in the polypeptide precursor. The channel is thus a pentameric core with the 'extra' subunits left out of the functional complex. From sedimentation equilibrium and size-exclusion chromatography, we also conclude that MscL complexes are not in a dynamic equilibrium with monomers, but are pre-assembled; and thus, their gating properties must result from changes in the conformation of the entire complex induced by the mechanical stress.

NASA Discipline Cell Biology↗

Objective and automated measurement of dynamic vision functions

A phoria stimulus array and electro-oculographic (EOG) arrangements for measuring motor and sensory responses of subjects subjected to stress or drug conditions are described, along with experimental procedures. Heterophoria (as oculomotor function) and glare recovery time (time required for photochemical and neural recovery after exposure to a flash stimulus) are measured, in research aimed at developing automated objective measurement of dynamic vision functions. Onset of involuntary optokinetic nystagmus in subjects attempting to track moving stripes (while viewing through head-mounted binocular eyepieces) after exposure to glare serves as an objective measure of glare recovery time.

Flom, M. C.↗

Time and motion, experiment M151

Astronaut work performance during the preparation and execution of experiments in simulated Skylab tests was analyzed according to time and motion in order to evaluate the efficiency and consistency of performance (adaptation function) for several different types of activity over the course of the mission; to evaluate the procedures to be used by the same experiment in Skylab; to generate characteristic adaptation functions for later comparison with Skylab data; and to examine astronaut performance for any behavioral stress due to the environment. The overall results indicate that the anticipated adaptation function was obtained both for individual and for averaged data.

Kubis, J. F.↗

Effects of the space flight environment on the immune system

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

NASA Discipline Regulatory Physiology↗

Modeling Progressive Failure of Bonded Joints Using a Single Joint Finite Element

Enhanced finite elements are elements with an embedded analytical solution which can capture detailed local fields, enabling more efficient, mesh-independent finite element analysis. In the present study, an enhanced finite element is applied to generate a general framework capable of modeling an array of joint types. The joint field equations are derived using the principle of minimum potential energy, and the resulting solutions for the displacement fields are used to generate shape functions and a stiffness matrix for a single joint finite element. This single finite element thus captures the detailed stress and strain fields within the bonded joint, but it can function within a broader structural finite element model. The costs associated with a fine mesh of the joint can thus be avoided while still obtaining a detailed solution for the joint. Additionally, the capability to model non-linear adhesive constitutive behavior has been included within the method, and progressive failure of the adhesive can be modeled by using a strain-based failure criteria and re-sizing the joint as the adhesive fails. Results of the model compare favorably with experimental and finite element results.

Stapleton, Scott E.↗

An evaluation of the effects of stacking sequence and thickness on the fatigue life of quasi-isotropic graphite/epoxy laminates

Notched and unnotched geometries at 16, 32, and 64-ply thicknesses of a 90/45/0-45 (ns) laminate and a 45/0/-45/90 (ns) laminate were tested in compression-compression fatigue. The fatigue life and the initiation, type, and progression of damage were determined. Interlaminar stresses generated at straight, free edges of axially loaded laminates were used to interpret the test results. The fatigue lives of the notched specimens did not appear to be a strong function of laminate stacking sequence or specimen thickness. The stress concentration at the hole dominated over the interlaminar stresses at the straight free edge. The unnotched specimens of the 90/45/0/-45 (ns) laminate with tensile interlaminar normal stresses delaminated more readily than did the 45/0/-45/90 (ns) laminate with compressive interlaminar normal stress. The life of the 16-ply unnotched specimens was lower than the 32- and 64-ply specimens. Delaminations were located at the interface where the maximum shear stress occurred regardless of the sense or magnitude of the interlaminar normal stress. An antibuckling fixture was effective in preventing out-of-plane motion without overconstraining the specimen.

Harris, C. E.↗

An evaluation of the effects of stacking sequence and thickness on the fatigue life of quasi-isotropic graphite/epoxy laminates

Notched and unnotched geometries at 16, 32, and 64-ply thicknesses of a 90/45/0-45 (ns) laminate and a 45/0/-45/90 (ns) laminate were tested in compression-compression fatigue. The fatigue life and the initiation, type, and progression of damage were determined. Interlaminar stresses generated at straight, free edges of axially loaded laminates were used to interpret the test results. The fatigue lives of the notched specimens did not appear to be a strong function of laminate stacking sequence or specimen thickness. The stress concentration at the hole dominated over the interlaminar stresses at the straight free edge. The unnotched specimens of the 90/45/0/-45 (ns) laminate with tensile interlaminar normal stresses delaminated more readily than did the 45/0/-45/90 (ns) laminate with compressive interlaminar normal stress. The life of the 16-ply unnotched specimens was lower than the 32and 64-ply specimens. Delaminations were located at the interface where the maximum shear stress occurred regardless of the sense or magnitude of the interlaminar normal stress. An antibuckling fixture was effective in preventing out-of-plane motion without overconstraining the specimen.

Harris, C. E.↗