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All sourcesNASA NTRSDOE OSTI
NASA NTRS1995

Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli.

Perrone, Carmen E.↗
NASA NTRS1972

Maximal Oxygen Uptake, Sweating and Tolerance to Exercise in the Heat

The physiological mechanisms that facilitate acute acclimation to heat have not been fully elucidated, but the result is the establishment of a more efficient cardiovascular system to increase heat dissipation via increased sweating that allows the acclimated man to function with a cooler internal environment and to extend his performance. Men in good physical condition with high maximal oxygen uptakes generally acclimate to heat more rapidly and retain it longer than men in poorer condition. Also, upon first exposure trained men tolerate exercise in the heat better than untrained men. Both resting in heat and physical training in a cool environment confer only partial acclimation when first exposed to work in the heat. These observations suggest separate additive stimuli of metabolic heat from exercise and environmental heat to increase sweating during the acclimation process. However, the necessity of utilizing physical exercise during acclimation has been questioned. Bradbury et al. (1964) have concluded exercise has no effect on the course of heat acclimation since increased sweating can be induced by merely heating resting subjects. Preliminary evidence suggests there is a direct relationship between the maximal oxygen uptake and the capacity to maintain thermal regulation, particularly through the control of sweating. Since increased sweating is an important mechanism for the development of heat acclimation, and fit men have high sweat rates, it follows that upon initial exposure to exercise in the heat, men with high maximal oxygen uptakes should exhibit less strain than men with lower maximal oxygen uptakes. The purpose of this study was: (1) to determine if men with higher maximal oxygen uptakes exhibit greater tolerance than men with lower oxygen uptakes during early exposure to exercise in the heat, and (2) to investigate further the mechanism of the relationship between sweating and maximal work capacity.

Greenleaf, J. E.↗
NASA NTRS1998

STS-90 Day 15 Highlights

On this fifteeth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk turns its attention to dexterity tests and dissections of rats neonates and the ball-catch experiment. Mission Specialists Rick Linnehan and Dave Williams and Payload Specialist Jim Pawelczyk will dissect the newborn rats. The dexterity test will test the response of young rats as they are tilted and turned while walking and climbing on a special apparatus with various surfaces. Later, all four payload crew members will repeat the ball-catch experiment. This experiment studies the ability of the central nervous system to accept and interpret new stimuli in space. The astronauts have performed this test at various points in the mission so scientists can compare their responses as their bodies adapt to weightlessness.

Source record↗
NASA NTRS1998

Human Physiological Responses to Cycle Ergometer Leg Exercise During +Gz Acceleration

Spaceflight and bed-rest deconditioning decrease maximal oxygen uptake (aerobic power), strength, endurance capacity, and orthostatic tolerance. In addition to extensive use of muscular exercise conditioning as a countermeasure for the reduction in aerobic power (VO(sub 2max)), stimuli from some form of +Gz acceleration conditioning may be necessary to attenuate the orthostatic intolerance component of this deconditioning. Hypothesis: There will be no significant difference in the physiological responses (oxygen uptake, heart rate, ventilation, or respiratory exchange ratio) during supine exercise with moderate +Gz acceleration.

Chou, J. L.↗
NASA NTRS1996

Coupled thermal/chemical/mechanical modeling of energetic materials in ALE3D

We must improve our ability to model the response of energetic materials to thermal stimuli and the processes involved in the energetic response. We have developed and used a time step option to efficiently and accurately compute the hours that the energetic material can take to react. Since on these longer film scales, materials can be expected to have significant motion, it is even more important to provide high-order advection for all components, including the chemical species. We show an example cook-off problem to illustrate these capabilities.

WEAPONS↗
NASA NTRS1996

Effect of Flow on Gene Regulation in Smooth Muscle Cells and Macromolecular Transport Across Endothelial Cell Monolayers

Endothelial cells line all of the vessels of the circulatory system, providing a non-thrombogenic conduit for blood flow; they regulate many complex functions in the vasculature, such as coagulation, fibrinolysis, platelet aggregation, vessel tone and growth, and leukocyte traffic; and they form the principal barrier to transport of substances between the blood and the surrounding tissue space. The permeability of endothelial cell changes with environmental stimuli; shear stress, in particular, applied either in vivo, or in vitro, induces changes in protein expression and secretion of vasoactive factors by endothelial cells. The ability to study the effects of shear on the macromolecular permeability of the cerebral vasculature is particularly important, since in no other place is the barrier function of the endothelium more important than in the brain. The endothelial cells of this organ have developed special barrier properties that keep the cerebral system from experiencing any drastic change in composition; together with glial cells, they form the blood brain barrier (BBB). We have studied the effect of flow on bovine BBB using flow chambers and tissue culture systems.

McIntire, Larry V.↗
NASA NTRS1997

Form and Objective of the Decision Rule in Absolute Identification

In several conditions of a line length identification experiment, the subjects' decision making strategies were systematically biased against the responses on the edges of the stimulus range. When the range and number of the stimuli were small, the bias caused the percentage of correct responses to be highest in the center and lowest on the extremes of the range. Two general classes of decision rules that would explain these results are considered. The first class assumes that subjects intend to adopt an optimal decision rule, but systematically misrepresent one or more parameters of the decision making context. The second class assumes that subjects use a different measure of performance than the one assumed by the experimenter: instead of maximizing the chances of a correct response, the subject attempts to minimize the expected size of the response error (a "fidelity criterion"). In a second experiment, extended experience and feedback did not diminish the bias effect, but explicitly penalizing all response errors equally, regardless of their size, did reduce or eliminate it in some subjects. Both results favor the fidelity criterion over the optimal rule.

Balakrishnan, J. D.↗
NASA NTRS1999

Investigating Interruptions: Implications for Flightdeck Performance

A fundamental aspect of multiple task management is attending to new stimuli and integrating associated task requirements into an ongoing task set; this is "interruption management" (IM). Anecdotal evidence and field studies indicate the frequency and consequences of interruptions, however experimental investigations of mechanisms influencing IM are scarce. Interruptions on commercial flightdecks are numerous, of various forms, and have been cited as contributing factors in many aviation incident and accident reports. This research grounds an experimental investigation of flightdeck interruptions in a proposed IM stage model. This model organizes basic research, identifies influencing mechanisms, and suggests appropriate dependent measures for IM. Fourteen airline pilots participated in a flightdeck simulation experiment to investigate the general effects of performing an interrupting task and interrupted procedure, and the effects of specific task factors: (1) modality; (2) embeddedness, or goal-level, of an interruption; (3) strength of association, or coupling-strength, between interrupted tasks; (4) semantic similarity; and (5) environmental stress. General effects of interruptions were extremely robust. All individual task factors significantly affected interruption management, except "similarity." Results extend the Interruption Management model, and are interpreted for their implications for interrupted flightdeck performance and intervention strategies for mitigating their effects on the flightdeck.

Latorella, Kara A.↗
NASA NTRS1999

The Role of Calcium in the Response of Osteoblasts to Mechanical Stimulation

A major biomedical concern in the exploration and development of space is the rapid loss of bone associated with extended periods of spaceflight. Mineral content, bone formation, matrix protein production and total body calcium are all reduced during long-term periods of weightlessness. These effects of weightlessness appears to be due to decreases in the anabolic function of osteoblasts and osteocytes rather than changes in the resorptive activity of osteoclasts. Conversely, subjecting the skeleton to exogenous mechanical loading increases matrix protein synthesis and bone formation rate, a process which also appears mediated through osteogenic cells. Osteoblasts have been shown to respond to a number of types of mechanical stimulation. However recently we have demonstrated that osteoblasts respond to fluid shear, but not physiologic levels of mechanical strain, with increases in expression of the matrix protein, osteopontin. We have also shown similar responses in other markers for the anabolic response in bone. The expression of the early response gene, c-fos, and the inducible-isoform of the prostaglandin synthetic enzyme, cyclooygenase-2 (COX-2), both increase rapidly in response to fluid shear, but not strain. How osteoblasts and osteocytes perceive mechanical stimuli and convert this stimulus into a biochemical event within the cell is still unknown. However, examination of the cellular events following mechanical stimulation indicate that two of the earliest responses are a rapid increase in intracellular calcium ([Ca(2+)](sub i)) and a reorganization of the actin cytoskeleton. The increase in [Ca(2+)](sub i) is dependent on the presence of extracellular Ca(2+), suggesting the activation of membrane Ca(2+) channel. We have previously characterized a mechanosensitive, cation-selective channel (MSCC) in osteoblast-like clonal cells, which we postulate is important in this early response to mechanical loading. Using an antisense oligodeoxynucleotide strategy, we have tentatively identified this channel as an isoform of the alc subunit of the dihydropyridine-sensitive, voltage sensitive Ca(2+) channel (VSCC). However, a major component in this mechanically induced rise in [Ca(2+)](sub i) is the release of Ca(2+) from intracellular stores. The actin cytoskeleton also rapidly responds to fluid shear with an increase in stress fiber formation and a realignment of the cell parallel to the direction of flow. To ascertain whether these two observations are related and how they effect shear-induced gene expression, we examined the role of Ca(2+) channels and intracellular Ca(2+) release on cytoskeletal reorganization and the resultant increases in the expression and production of c-fos and COX-2 in response to fluid shear.

Duncan, R. L.↗
NASA NTRS1999

Self-Motion Perception: Assessment by Real-Time Computer Generated Animations

Our overall goal is to develop materials and procedures for assessing vestibular contributions to spatial cognition. The specific objective of the research described in this paper is to evaluate computer-generated animations as potential tools for studying self-orientation and self-motion perception. Specific questions addressed in this study included the following. First, does a non- verbal perceptual reporting procedure using real-time animations improve assessment of spatial orientation? Are reports reliable? Second, do reports confirm expectations based on stimuli to vestibular apparatus? Third, can reliable reports be obtained when self-motion description vocabulary training is omitted?

Parker, Donald E.↗
NASA NTRS1999

Molecular Signaling in Muscle Plasticity

Extended spaceflight under microgravity conditions leads to significant atrophy of weight-bearing muscles. Atrophy and hypertrophy are the extreme outcomes of the high degree of plasticity exhibited by skeletal muscle. Stimuli which control muscle plasticity include neuronal, hormonal, nutritional, and mechanical inputs. The mechanical stimulus for muscle is directly related to the work or exercise against a load performed. Little or no work is performed by weight-bearing muscles under microgravity conditions. A major hypothesis is that focal adhesion kinase (FAK) which is associated with integrin at the adherens junctions and costa meres of all skeletal muscles is an integral part of the major mechanism for molecular signaling upon mechanical stimulation in all muscle fibers. Additionally, we propose that myotonic protein kinase (DMPK) and dystrophin (DYSTR) also participate in distinct mechanically stimulated molecular signaling pathways that are most critical in type I and type II muscle fibers, respectively. To test these hypotheses, we will use the paradigms of hindlimb unloading and overloading in mice as models for microgravity conditions and a potential exercise countermeasure, respectively, in mice. We expect that FAK loss-of-function will impair hypertrophy and enhance atrophy in all skeletal muscle fibers whereas DYSTR and DMPK loss-of-function will have similar but more selective effects on Type IT and Type I fibers, respectively. Gene expression will be monitored by muscle-specific creatine kinase M promoter-reporter construct activity and specific MRNA and protein accumulation in the soleus (type I primarily) and plantaris (type 11 primarily) muscles. With these paradigms and assays, the following Specific Project Aims will be tested in genetically altered mice: 1) identify the roles of DYSTR and its pathway; 2) evaluate the roles of the DMPK and its pathway; 3) characterize the roles of FAK and its pathway and 4) genetically analyze the mechanisms and interactions between the FAK, DYSTR, and DMPK-associated pathways in single and specific combinations of mutants. The identification of potential signaling mechanisms may permit future development of pharmacological countermeasures for amelioration and prevention of the microgravity-induced atrophy in extended spaceflight, and the analysis of both overloading and unloading paradigms may provide further support for development of exercise-based countermeasures. Understanding the basic mechanisms of molecular signaling in muscle plasticity may aid our understanding and treatment of skeletal muscle atrophy not only in spaceflight but in similar problems of the aging population, in prolonged bed rest, and in cachexia associated with chronic disease.

Epstein, Henry F.↗
NASA NTRS2000

A Review of Electrical Impedance Spectrometry Methods for Parametric Estimation of Physiologic Fluid Volumes

Electrical impedance spectrometry involves measurement of the complex resistance of a load at multiple frequencies. With this information in the form of impedance magnitude and phase, or resistance and reactance, basic structure or function of the load can be estimated. The "load" targeted for measurement and estimation in this study consisted of the water-bearing tissues of the human calf. It was proposed and verified that by measuring the electrical impedance of the human calf and fitting this data to a model of fluid compartments, the lumped-model volume of intracellular and extracellular spaces could be estimated, By performing this estimation over time, the volume dynamics during application of stimuli which affect the direction of gravity can be viewed. The resulting data can form a basis for further modeling and verification of cardiovascular and compartmental modeling of fluid reactions to microgravity as well as countermeasures to the headward shift of fluid during head-down tilt or spaceflight.

Dewberry, B.↗
NASA NTRS1996

Ground Reaction Forces During Locomotion in Simulated Microgravity

Significant losses in bone density and mineral, primarily in the lower extremities have been reported following exposure to weightlessness. Recent investigations suggest that mechanical influences such as bone deformation and strain rate may be critically important in stimulating new bone formation. It was hypothesized that velocity, cadence and harness design would significantly affect lower limb impact forces during treadmill exercise in simulated zero gravity (0G). A ground-based hypogravity simulator was used to investigate which factors affect limb loading during tethered treadmill exercise. A fractional factorial design was used and 12 subjects were studied. The results showed that running on active and passive treadmills in the simulator with a tethering force close to the maximum comfortable level produced similar magnitudes for the peak ground reaction force. It was also found that these maximum forces were significantly lower than those obtained during overground trials, even when the speeds of locomotion in the simulator were 66 % greater than those in 1 G. Cadence had no effect on any of the response variables. The maximum rate of force application (DFDT-Max) was similar for overground running and exercise in simulated 0G, provided that the "weightless subjects ran on a motorized treadmill. These findings have implications for the use of treadmill exercise as a countermeasure for hypokinetic osteoporosis. As the relationship between mechanical factors and osteogenesis becomes better understood, results from human experiments in 0G simulators will help to design in-flight exercise programs that are more closely targeted to generate appropriate mechanical stimuli.

Davis, B. L.↗
NASA NTRS1985

The Radioimmunoassay of Fluid and Electrolyte Hormones

The subject of the paper will be the assay of fluid/electrolyte hormones. ADH (antidiuretic hormone also referred to as vasopressin) reduces fluid loss by increasing water reabsorption by the kidney. The stimuli for its release from the pituitary are loss of blood, dehydration, or increased salt intake. Angiotensin II is the next hormone of interest. It is "generated" from a blood protein by the release of renin from the kidney. One of its functions is to stimulate the secretion of aldosterone from the adrenal gland. Release of renin is also stimulated by volume and sodium loss.

Keil, Lanny C.↗
NASA NTRS1985

Electroencephalogram (EEG) and Magnetoencephalogram (MEG) as Tools for Evaluation of Cognitive Function

We have developed computerized analysis and display techniques to help identify the origins of visually evoked scalped potentials (VESP). The potentials are recorded simultaneously from many electrodes (usually 40 to 48) spaced over the region of the scalp where appreciable evoked potentials are found in response to particular stimulus. Contour mapping algorithms are then used to display the time behavior of equipotential surfaces on the scalp during the VESP. We then use an optimization technique to select the parameters of arrays of current dipole sources within the model until the model equipotential field distribution closely fits the measured data. Computer graphics are then used to display, as a movie, the actual and model scalp potential fields and the parameters of the dipole generators within the model head during the course of VESP activity. We have devised reaction time tests that involve potentially separable stages of cognitive processing and utilize stimuli that produce measurable cognition-related features in the late component of the evoked potential. We have used these techniques to determine the loci in the brain where known cognition-related features in the evoked potential are generated and we have explored the extent to which each of these features can be related to the reaction time tasks. We have also examined the temporal-spatial aspects of their cerebral involvement. Our current work is planned to characterize the age-related changes in the processes performed by such sources. We also use a neuromagnetometer to measure the evoked magnetic fields in similar circumstances; we will discuss the relative merits of the two methodologies.

Fender, Derek H.↗
NASA NTRS1999

JANNAF 18th Propulsion Systems Hazards Subcommittee Meeting

This volume, the first of two volumes is a compilation of 18 unclassified/unlimited-distribution technical papers presented at the Joint Army-Navy-NASA-Air Force (JANNAF) 18th Propulsion Systems Hazards Subcommittee (PSHS) meeting held jointly with the 36th Combustion Subcommittee (CS) and 24th Airbreathing Propulsion Subcommittee (APS) meetings. The meeting was held 18-21 October 1999 at NASA Kennedy Space Center and The DoubleTree Oceanfront Hotel, Cocoa Beach, Florida. Topics covered at the PSHS meeting include: shaped charge jet and kinetic energy penetrator impact vulnerability of gun propellants; thermal decomposition and cookoff behavior of energetic materials; violent reaction; detonation phenomena of solid energetic materials subjected to shock and impact stimuli; and hazard classification, insensitive munitions, and propulsion systems safety.

Cocchiaro, James E.↗
NASA NTRS2000

T Lymphocyte Activation Threshold is Increased in Reduced Gravity

There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

Adams, Charley L.↗
NASA NTRS1999

Spatial Orientation and Balance Control Changes Induced by Altered Gravito-Inertial Force Vectors

Seventeen healthy and eight vestibular deficient subjects were exposed to an interaural centripetal acceleration of 1 G (resultant 45 deg roll tilt of 1.4 G) on a 0.8 meter radius centrifuge for a period of 90 minutes in the dark. The subjects sat with head fixed upright, except every 4 of 10 minutes when instructed to rotate their head so that their nose and eyes pointed towards a visual point switched on every 3 to 5 seconds at random places (within +/- 30 deg) in the Earth horizontal plane. Motion sickness caused some subjects to limit their head movements during significant portions of the 90 minute period, and led three normal subjects to stop the test earlier. Eye movements, including directed saccades for subjective Earth- and head-referenced planes, were recorded before, during, and immediately after centrifugation using electro-oculography. Postural stability measurements were made before and within ten minutes after centrifugation. In normal subjects, postural sway and multisegment body kinematics were gathered during an eyes-closed head movement cadence (sway-referenced support platform), and in response to translational/rotational platform perturbations. A significant increase in postural sway, segmental motion amplitude and hip frequency was observed after centrifugation. This effect was short-lived, with a recovery time of several postural test trials. There were also asymmetries in the direction of post-centrifugation center of sway and head tilt which depended on the subject's orientation during the centrifugation adaptation period (left ear or right ear out). To delineate the effect of the magnitude of the gravito-inertial vector versus its direction during the adaptive centrifugation period, we tilted eight normal subjects in the roll axis at a 45 deg angle in the dark for 90 minutes without rotational motion. Their postural responses did not change following the period of tilt. Based on verbal reports, normal subjects overestimated roll-tilt during 90 minutes of both tilt and centrifugation stimuli. Subjective estimates of head-horizontal, provided by directed saccades, revealed significant errors after approximately 30 minutes that tended to increase only in the group who underwent centrifugation. Immediately after centrifugation, subjects reported feeling tilted on average 10 degrees in the opposite direction, which was in agreement with the direction of their earth-directed saccades. In vestibular deficient (VD) subjects, postural sway was measured using a sway-referenced or earth-fixed support surface, and with or without a head movement sequence. 'Me protocol was selected for each patient during baseline testing, and corresponded to the most challenging condition in which the patient was able to maintain balance with eyes closed. Bilaterally VD subjects showed no postural decrement after centrifugation, while unilateral VD subjects had varying degrees of decrement. Unilateral VD subjects were tested twice; they underwent centrifugation both with right ear out and left ear out. Their post-centrifuation center of sway shifted at right angles depending on the centrifuge GIF orientation. Bilateral VD subjects bad shifts as well, but no consistent directional trend. VD subjects underestimated roll-tilt during centrifugation, These results suggest that orientation of the gravito-inertial vector and its magnitude arc both used by the central nervous system for calibration of multiple orientation systems. A change in the background gravito-inertial force (otolith input) can rapidly initiate postural and perceptual adaptation in several sensorimotor systems, independent of a structured visual surround.

Kaufman, Galen D.↗