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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 235 records · Page 13

Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

NASA Discipline Neuroscience↗

Classification image analysis: estimation and statistical inference for two-alternative forced-choice experiments

We consider estimation and statistical hypothesis testing on classification images obtained from the two-alternative forced-choice experimental paradigm. We begin with a probabilistic model of task performance for simple forced-choice detection and discrimination tasks. Particular attention is paid to general linear filter models because these models lead to a direct interpretation of the classification image as an estimate of the filter weights. We then describe an estimation procedure for obtaining classification images from observer data. A number of statistical tests are presented for testing various hypotheses from classification images based on some more compact set of features derived from them. As an example of how the methods we describe can be used, we present a case study investigating detection of a Gaussian bump profile.

Non-NASA Center↗

Application of multivariate statistics to vestibular testing: discriminating between Meniere's disease and migraine associated dizziness

Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

NASA Discipline Neuroscience↗

Altered sensory-motor control of the head as an etiological factor in space-motion sickness

Mechanical unloading during head movements in weightlessness may be an etiological factor in space-motion sickness. We simulated altered head loading on Earth without affecting vestibular stimulation by having subjects wear a weighted helmet. Eight subjects were exposed to constant velocity rotation about a vertical axis with direction reversals every 60 sec. for eight reversals with the head loaded and eight with the head unloaded. The severity of motion sickness elicited was significantly higher when the head was loaded. This suggests that altered sensory-motor control of the head is also an etiological factor in space-motion sickness.

NASA Discipline Neuroscience↗

A simulator for evaluating methods for the detection of lesion-deficit associations

Although much has been learned about the functional organization of the human brain through lesion-deficit analysis, the variety of statistical and image-processing methods developed for this purpose precludes a closed-form analysis of the statistical power of these systems. Therefore, we developed a lesion-deficit simulator (LDS), which generates artificial subjects, each of which consists of a set of functional deficits, and a brain image with lesions; the deficits and lesions conform to predefined distributions. We used probability distributions to model the number, sizes, and spatial distribution of lesions, to model the structure-function associations, and to model registration error. We used the LDS to evaluate, as examples, the effects of the complexities and strengths of lesion-deficit associations, and of registration error, on the power of lesion-deficit analysis. We measured the numbers of recovered associations from these simulated data, as a function of the number of subjects analyzed, the strengths and number of associations in the statistical model, the number of structures associated with a particular function, and the prior probabilities of structures being abnormal. The number of subjects required to recover the simulated lesion-deficit associations was found to have an inverse relationship to the strength of associations, and to the smallest probability in the structure-function model. The number of structures associated with a particular function (i.e., the complexity of associations) had a much greater effect on the performance of the analysis method than did the total number of associations. We also found that registration error of 5 mm or less reduces the number of associations discovered by approximately 13% compared to perfect registration. The LDS provides a flexible framework for evaluating many aspects of lesion-deficit analysis.

NASA Program Biomedical Research and Countermeasur↗

Age dependency of base modification in rabbit liver DNA

Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

NASA Discipline Radiation Health↗

Life Sciences Data Archive Scientific Development

The Life Sciences Data Archive will provide scientists, managers and the general public with access to biomedical data collected before, during and after spaceflight. These data are often irreplaceable and represent a major resource from the space program. For these data to be useful, however, they must be presented with enough supporting information, description and detail so that an interested scientist can understand how, when and why the data were collected. The goal of this contract was to provide a scientific consultant to the archival effort at the NASA-Johnson Space Center. This consultant (Jay C. Buckey, Jr., M.D.) is a scientist, who was a co-investigator on both the Spacelab Life Sciences-1 and Spacelab Life Sciences-2 flights. In addition he was an alternate payload specialist for the Spacelab Life Sciences-2 flight. In this role he trained on all the experiments on the flight and so was familiar with the protocols, hardware and goals of all the experiments on the flight. Many of these experiments were flown on both SLS-1 and SLS-2. This background was useful for the archive, since the first mission to be archived was Spacelab Life Sciences-1. Dr. Buckey worked directly with the archive effort to ensure that the parameters, scientific descriptions, protocols and data sets were accurate and useful.

Buckey, Jay C., Jr.↗

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Review↗

Modeling beta-adrenergic control of cardiac myocyte contractility in silico

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

Non-NASA Center↗

Sculpturing new muscle phenotypes

Changes in the pattern of muscle activity are followed by new patterns of protein synthesis, both in the contractile elements and in the enzymes of energy metabolism. Although the signal transducers have not been identified, techniques of molecular biology have clearly shown that the adaptive responses are the regulated consequence of differential gene expression.

Non-NASA Center↗

Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

Clinical Trial↗

Dynamic markers of altered gait rhythm in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a disorder marked by loss of motoneurons. We hypothesized that subjects with ALS would have an altered gait rhythm, with an increase in both the magnitude of the stride-to-stride fluctuations and perturbations in the fluctuation dynamics. To test for this locomotor instability, we quantitatively compared the gait rhythm of subjects with ALS with that of normal controls and with that of subjects with Parkinson's disease (PD) and Huntington's disease (HD), pathologies of the basal ganglia. Subjects walked for 5 min at their usual pace wearing an ankle-worn recorder that enabled determination of the duration of each stride and of stride-to-stride fluctuations. We found that the gait of patients with ALS is less steady and more temporally disorganized compared with that of healthy controls. In addition, advanced ALS, HD, and PD were associated with certain common, as well as apparently distinct, features of altered stride dynamics. Thus stride-to-stride control of gait rhythm is apparently compromised with ALS. Moreover, a matrix of markers based on gait dynamics may be useful in characterizing certain pathologies of motor control and, possibly, in quantitatively monitoring disease progression and evaluating therapeutic interventions.

NASA Program Biomedical Research and Countermeasur↗

Inducing jet-lag in older people: directional asymmetry

Twenty healthy elderly subjects (12 female, 8 male; mean age 81 years, range 67-87 years) each experienced a 15-day time isolation protocol in which they lived individually in a special laboratory apartment in which sleep and circadian rhythm measures could be taken. There were two experiments: one (6 females, 4 males) involved a 6-h phase advance of the sleep/wake cycle, and the other (6 females, 4 males) a 6-h phase delay. Each started with 5 baseline days, immediately followed by the phase shift. The subject was then held to the phase shifted routine for the remainder of the study. Rectal temperatures were recorded minute-by-minute throughout the entire experiment and each night of sleep was recorded using polysomnography. A directional asymmetry in phase-shift effects was apparent, with significantly more sleep disruption and circadian rhythm amplitude disruption after the phase advance than after the phase delay. Sleep disruption was reflected in reduced time spent asleep, and in changed REM latency, which increased in the phase advance direction but decreased in the phase delay direction. Although the phase advance led to a significant increase in wakefulness in the first half of the night, the phase delay did not lead to an equivalent increase in wakefulness during the second half of the night. Examination of both raw and 'demasked' circadian rectal temperature rhythms confirmed that phase adjustment was slow in both directions, but was less slow (and more monotonic) after the phase delay than after the phase advance. Subjective alertness suffered more disruption after the phase advance than after the phase delay.

NASA Discipline Regulatory Physiology↗

Postural control model interpretation of stabilogram diffusion analysis

Collins and De Luca [Collins JJ. De Luca CJ (1993) Exp Brain Res 95: 308-318] introduced a new method known as stabilogram diffusion analysis that provides a quantitative statistical measure of the apparently random variations of center-of-pressure (COP) trajectories recorded during quiet upright stance in humans. This analysis generates a stabilogram diffusion function (SDF) that summarizes the mean square COP displacement as a function of the time interval between COP comparisons. SDFs have a characteristic two-part form that suggests the presence of two different control regimes: a short-term open-loop control behavior and a longer-term closed-loop behavior. This paper demonstrates that a very simple closed-loop control model of upright stance can generate realistic SDFs. The model consists of an inverted pendulum body with torque applied at the ankle joint. This torque includes a random disturbance torque and a control torque. The control torque is a function of the deviation (error signal) between the desired upright body position and the actual body position, and is generated in proportion to the error signal, the derivative of the error signal, and the integral of the error signal [i.e. a proportional, integral and derivative (PID) neural controller]. The control torque is applied with a time delay representing conduction, processing, and muscle activation delays. Variations in the PID parameters and the time delay generate variations in SDFs that mimic real experimental SDFs. This model analysis allows one to interpret experimentally observed changes in SDFs in terms of variations in neural controller and time delay parameters rather than in terms of open-loop versus closed-loop behavior.

NASA Program Biomedical Research and Countermeasur↗

Evidence of SV40 infections in hospitalized children

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

NASA Discipline Regulatory Physiology↗

Effect of viewing distance on the generation of vertical eye movements during locomotion

Vertical head and eye coordination was studied as a function of viewing distance during locomotion. Vertical head translation and pitch movements were measured using a video motion analysis system (Optotrak 3020). Vertical eye movements were recorded using a video-based pupil tracker (Iscan). Subjects (five) walked on a linear treadmill at a speed of 1.67 m/s (6 km/h) while viewing a target screen placed at distances ranging from 0.25 to 2.0 m at 0. 25-m intervals. The predominant frequency of vertical head movement was 2 Hz. In accordance with previous studies, there was a small head pitch rotation, which was compensatory for vertical head translation. The magnitude of the vertical head movements and the phase relationship between head translation and pitch were little affected by viewing distance, and tended to orient the naso-occipital axis of the head at a point approximately 1 m in front of the subject (the head fixation distance or HFD). In contrast, eye velocity was significantly affected by viewing distance. When viewing a far (2-m) target, vertical eye velocity was 180 degrees out of phase with head pitch velocity, with a gain of 0. 8. This indicated that the angular vestibulo-ocular reflex (aVOR) was generating the eye movement response. The major finding was that, at a close viewing distance (0.25 m), eye velocity was in phase with head pitch and compensatory for vertical head translation, suggesting that activation of the linear vestibulo-ocular reflex (lVOR) was contributing to the eye movement response. There was also a threefold increase in the magnitude of eye velocity when viewing near targets, which was consistent with the goal of maintaining gaze on target. The required vertical lVOR sensitivity to cancel an unmodified aVOR response and generate the observed eye velocity magnitude for near targets was almost 3 times that previously measured. Supplementary experiments were performed utilizing body-fixed active head pitch rotations at 1 and 2 Hz while viewing a head-fixed target. Results indicated that the interaction of smooth pursuit and the aVOR during visual suppression could modify both the gain and phase characteristics of the aVOR at frequencies encountered during locomotion. When walking, targets located closer than the HFD (1.0 m) would appear to move in the same direction as the head pitch, resulting in suppression of the aVOR. The results of the head-fixed target experiment suggest that phase modification of the aVOR during visual suppression could play a role in generating eye movements consistent with the goal of maintaining gaze on targets closer than the HFD, which would augment the lVOR response.

NASA Discipline Neuroscience↗

Exploration Medical Capability (ExMC) Projects

During missions to the Moon or Mars, the crew will need medical capabilities to diagnose and treat disease as well as for maintaining their health. The Exploration Medical Capability Element develops medical technologies, medical informatics, and clinical capabilities for different levels of care during space missions. The work done by team members in this Element is leading edge technology, procedure, and pharmacological development. They develop data systems that protect patient's private medical information, aid in the diagnosis of medical conditions, and act as a repository of relevant NASA life sciences experimental studies. To minimize the medical risks to crew health the physicians and scientists in this Element develop models to quantify the probability of medical events occurring during a mission. They define procedures to treat an ill or injured crew member who does not have access to an emergency room and who must be cared for in a microgravity environment where both liquids and solids behave differently than on Earth. To support the development of these medical capabilities, the Element manages the development of medical technologies that prevent, monitor, diagnose, and treat an ill or injured crewmember. The Exploration Medical Capability Element collaborates with the National Space Biomedical Research Institute (NSBRI), the Department of Defense, other Government-funded agencies, academic institutions, and industry.

Wu, Jimmy↗

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the world's space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organism's self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as "pathfinders," which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes. In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

metabilic flexibility↗