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NASA NTRS2000

Role of Integrin in Mechanical Loading of Osteoblasts

Mechanical forces generated by gravity, weightbearing, and muscle contraction play a key role in the genesis and maintenance of skeletal structure. The molecular mechanisms that mediate changes in osteoblast activity in response to altered patterns of skeletal loading are not known, and a better understanding of these processes may be essential for developing effective treatment strategies to prevent disuse osteoporosis. We have elucidated specific integrin/ECM (extracellular matrix) interactions that are required for osteoblast differentiation and survival and have developed a useful loading system to further explore the molecular basis of mechano-sensitivity of osteoblasts. The long term goal of our collaborative research is to understand how the ECM and cell adhesion proteins and integrins interaction to mediate the response of osteoblasts and their progenitors to mechanical loading. We suggest that integrin/ECM interactions are crucial for basic cellular processes, including differentiation and survival, as well as to participate in detecting and mediating cellular responses to mechanical stimuli.

Globus, Ruth↗
NASA NTRS1994

Distance Perception of Stereoscopically Presented Virtual Objects Optically Superimposed on Physical Objects by a Head-Mounted See-Through Display

The influence of physically presented background stimuli on the perceived depth of optically overlaid, stereoscopic virtual images has been studied using headmounted stereoscopic, virtual image displays. These displays allow presentation of physically unrealizable stimulus combinations. Positioning of an opaque physical object either at the initial perceived depth of the virtual image or at a position substantially in front of the virtual image, causes the virtual image to perceptually move closer to the observer. In the case of objects positioned substantially in front of the virtual image, subjects often perceive the opaque object to become transparent. Evidence is presented that the apparent change of position caused by interposition of the physical object is not due to occlusion cues. According, it may have an alternative cause such as variation in the binocular vengeance position of the eyes caused by introduction of the physical object. This effect may complicate design of overlaid virtual image displays for near objects and appears to be related to the relative conspicuousness of the overlaid virtual image and the background. Consequently, it may be related to earlier analyses of John Foley which modeled open-loop pointing errors to stereoscopically presented points of light in terms of errors in determination of a reference point for interpretation of observed retinal disparities. Implications for the design of see-through displays for manufacturing will be discussed.

Ellis, Stephen R.↗
NASA NTRS2000

Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

Globus, Ruth K.↗
NASA NTRS2000

Deconditioning and Reconditioning: Humans in Stressful Environments

Deconditioning is an integrated physiological response of the body to a reduction in metabolic rate; that is, to a reduction in energy use or in exercise level. While it may involve assumption of a horizontal body position, it certainly perturbs bodily homeostasis - at least temporarily. The reduction in physical activity that causes deconditioning is often associated with an increase in the time spent, for whatever reason, in a sitting or horizontal position. As a result, orthostatic factors may also contribute to the deconditioning mechanism. The word decondition may be defined as "1: to cause extinction of (a conditioned response) 2: to cause to lose physical fitness". This definition implies that psychological/emotional factors may accompany physical deconditioning, and it is this interpretation of the word that is used throughout this volume. It is apparent that deconditioning plays a major role in the mechanism of the general adaptive (homeostatic) response that is initiated by exposure to prolonged bed rest (BR). And the total homeostatic response to BR involves more than deconditioning per se. For example, it has been shown that the restoration of plasma volume and maximal work capacity after 4 weeks of BR deconditioning left other bodily functions (submaximal exercise oxygen uptake and cardiac output, leg proprioception and posterior leg muscle thickness and volume, head-up tilt tolerance, and sleep quality) functioning at decreased levels. The precise effect of deconditioning on BR homeostasis is difficult to determine, because the fundamental interactive neuro-endocrine-immune control networks that facilitate conditioning and deconditioning also act to maintain basic wholebody homeostasis. For example, is the mechanism of BR-induced deconditioning independent of the mechanism that provokes concomitant orthostatic intolerance; that is, fainting? Assumption of the recumbent body position for prolonged periods of time, results in a new adaptive-homeostatic state. This state occurs in response to the mutually interactive effects of the change in bodily position (hydrostatic pressure), to the virtual elimination of longitudinal pressure on the bones, to the increased confinement with possible reduction in total daily energy (exercise) expenditure, to the reorientation of stimuli within the vestibular organs, and (often) to altered socio-psychological conditions. The exercise-training (reconditioning) syndrome affects total body homeostasis by facilitating increases in work capacity and endurance, whereas deconditioning decreases physical performance. There are many interrelated factors that influence the control parameters that seek to maintain the adaptive conditioning-deconditioning syndrome. These control parameters can be better elucidated by subjecting otherwise healthy ambulatory people to various stresses, such as exercise training and prolonged spaceflight, bed rest, water immersion, hyperbaria, and isolation and confinement. Changes in control parameters will be manifested in muscle function, orthostatic tolerance, cardiorespiratory responses, musculo-skeletal systems, free-radical processes, and body thermoregulation with overarching effects on the subjects' psycho-sociological states. A discussion of these factors and the control parameters constitutes the substance of this volume. Special emphasis is placed on delineating practical applications of the findings that will be of special interest to physicians, nurses, and other health-care workers.

Greenleaf, John E.↗
NASA NTRS1994

A Role for MST Neurons in Heading Estimation

A template model of human visual self-motion perception (Perrone, JOSA, 1992; Perrone & Stone, Vis. Res., in press), which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results (Warren & Hannon, Nature, 1988; Stone & Perrone, Neuro. Abstr., 1991) including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions (Royden et al., Nature, 1992). We tested the model detectors with stimuli used by others in- single-unit studies. The detectors showed emergent properties similar to those of MST neurons: 1) Sensitivity to non-preferred flow. Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow (Orban et al., PNAS, 1992), and 2) Position invariance. The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields (e.g. Duffy & Wurtz, J. Neurophys., 1991; Graziano et al., J. Neurosci., 1994). It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Stone, Leland Scott↗
NASA NTRS1994

Assessment of Psychophysiological Responses During Motion Sickness Testing

The purpose of this investigation is to evaluate a methodology designed to accurately trace the temporal progression of motion sickness and space motion sickness symptoms. With this method, subjects continuously monitor their own motion sickness symptoms during exposure to a provocative stimulus as symptoms occur, in contrast to previous methods during which subjects report symptoms verbally at discrete time intervals. This method not only is comparable to previous methods in the type of symptoms that subjects report, but subjects report symptoms more frequently. Frequent reporting of motion sickness symptoms allows researchers to detail the waxing and waning of motion sickness symptoms for each individual. Previous research has shown that physiological responses to motion sickness stimuli are characterized by unique individual differences in response patterns. By improving our assessment of motion sickness symptoms with continuous monitoring of symptoms, the relationship between specific physiological responses and sickness levels can be more accurately determined for each individual. Results from this study show significant positive relationships between skin conductance levels and symptom levels for ten individuals; a significant positive relationship between temperature and symptom levels for 5 of 10 individuals; and both positive and negative relationships between respiration, heart rate, blood volume pulse and symptom levels. Continuous monitoring of motion sickness symptoms can be used to more accurately assess motion sickness to aid in the evaluation of countermeasures. In addition, recognition of the onset of symptoms that are strongly related to specific physiological responses could be used as cues to initiate procedures (e.g., Autogenic Feedback Training) to prevent the development of severe motion sickness symptoms.

Stoud, Cynthia S.↗
NASA NTRS2001

How Cyanobacterial Distributions Reveal Flow and Irradiance Conditions of Photosynthetic Biofilm Formation

Microbial life on Earth is enormously abundant at sediment-water interfaces. The fossil record in fact contains abundant evidence of the preservation of life on such surfaces. It is therefore critical to our interpretation of early Earth history, and potentially to history of life on other planets, to be able to recognize life forms at these interfaces. On Earth this life often occurs as organized structures of microbes and their extracellular exudates known as biofilms. When such biofilms occur in areas receiving sunlight photosynthetic biofilms are the dominant form in natural ecosystems due to selective advantage inherent in their ability to utilize solar energy. Cyanobacteria are the dominant phototrophic microbes in most modern and ancient photosynthetic biofilms, microbial mats and stromatolites. Due to their long (3.5 billion year) evolutionary history, this group has extensively diversified resulting in an enormous array of morphologies and physiological abilities. This enormous diversity and specialization results in very specific selection for a particular cyanobacterium in each available photosynthetic niche. Furthermore these organisms can alter their spatial orientation, cell morphology, pigmentation and associations with heterotrophic organisms in order to fine tune their optimization to a given micro-niche. These adaptations can be detected, and if adequate knowledge of the interaction between environmental conditions and organism response is available, the detectable organism response can be used to infer the environmental conditions causing that response. This presentation will detail two specific examples which illustrate this point. Light and water are essential to photosynthesis in cyanobacteria and these organisms have specific detectable behavioral responses to these parameters. We will present cyanobacterial responses to quantified flow and irradiance to demonstrate the interpretative power of distribution and orientation information. This study presents new results, but many such examples are already found in the literature. However this information exists in such a wide variety of journals, spanning decades of research that the utility of the vast storehouse of information is limited, not by the ability of cyanobacteria to respond in recognizable ways to environmental stimuli, but by our ability to compile and use this information. Recent advances in information technology will soon allow us to overcome these difficulties and utilize the detailed responses of cyanobacteria to environmental microniches as powerful records of the interaction between the biosphere and lithosphere.

Prufert-Bebout, Lee↗
NASA NTRS1994

Virtual Acoustic Displays for Teleconferencing: Intelligibility Advantage for "Telephone Grade" Audio

Speech intelligibility was evaluated using a virtual acoustic ("3-D audio") display using the method specified by ANSI. Ten subjects were evaluated with stimuli either unfiltered or low-pass filtered at 4 kHz. Results show virtual acoustic techniques are advantageous for both full-bandwidth (44.1 kHz srate) and low (8 kHz srate) bandwidth "telephone-grade" teleconferencing systems.

Begault, Durand R.↗
NASA NTRS1994

A Role for MST Neurons in Heading Estimation

A template model of human visual self-motion perception, which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions. We tested the model detectors with stimuli used by others in single-unit studies. The detectors showed emergent properties similar to those of MST neurons: (1) Sensitivity to non-preferred flow; Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow, and (2) Position invariance; The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields. It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Stone, L. S.↗
NASA NTRS1995

'Party Line' Information Use Studies and Implications for ATV Datalink Communications

The perceived importance and utilization of 'party line' information by air carrier flight crews was investigated through pilot surveys and a flight simulation study. The Importance, Availability, and Accuracy of party line information elements were explored through surveys of pilots of several operational types. The survey identified numerous traffic and weather party line information elements which were considered important. These elements were scripted into a full-mission flight simulation which examined the utilization of party line information by studying subject responses to specific information element stimuli. The awareness of the different Party Line elements varied, and awareness was also affected by pilot workload. In addition, pilots were aware of some traffic information elements, but were reluctant to act on Party Line Information alone. Finally, the importance of party line information appears to be greatest for operations near or on the airport. This indicates that caution should be exercised when implementing datalink communications in tower and close-in terminal control sectors.

Pritchett, Amy↗
NASA NTRS1995

"Party Line" Information Use Studies and Implications for ATC Datalink Communications

The perceived importance and utilization of 'party line' information by air carrier flight crews was investigated through pilot surveys and a flight simulation study. The importance, availability, and accuracy of party line information elements were explored through surveys of pilots of several operational types. The survey identified numerous traffic and weather party line information elements which were considered important. These elements were scripted into a full-mission flight simulation which examined the utilization of party line information by studying subject responses to specific information element stimuli. The awareness of the different Party Line elements varied, and awareness was also affected by pilot workload. In addition, pilots were aware of some traffic information elements, but were reluctant to act on Party Line Information alone. Finally, the results of both the survey and the simulation indicated that the importance of party line information appeared to be greatest for operations near or on the airport. This indicates that caution should be exercised when implementing datalink communications in tower and close-in terminal control sectors.

Hansman, R. John↗
NASA NTRS1995

The PRP Effect Following Callosotomy: Residual Interference Despite Uncoupling of Lateralized Response Codes

A callosotomy patient was tested in two dual-task experiments requiring successive speeded responses to lateralized stimuli. In accord with the recent findings of Pashler, O'Brien, Luck, Hillyard, Mangun, and Gazzaniga (in press), the patient showed a robust psychological refractory period effect (PRP) responses on Task 2 were inversely related to the stimulus-onset asynchrony (SOA). However, three aspects of our data indicated that the processing limitations for the patient were different than those observed with control subjects. First, the split-brain patient did not show an increase in reaction time when the two tasks required responses from a common output system (i.e., both manual responses) in comparison to when different output systems were used (i.e., manual-vocal). Second, inconsistent stimulus-response mappings for the two tasks greatly inflated response latencies for the control subjects, but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with SOA for only the patient, suggesting a later bottleneck in processing following callosotomy than was observed for the control subjects. It is proposed that sectioning the corpus callosum eliminates interference resulting from competing stimulus response codes. Nonetheless, dual-task interference persists for the split-brain subject because a subcortical gate constrains when selected responses can be implemented.

Ivry, Richard B.↗
NASA NTRS1996

Quantifying the Correlation Between Eye-Movement and Perceptual Responses to Moving Plaids

To determine the extent to which the pursuit eye-movement and perceptual systems share a common neural motion-processing pathway, we simultaneously measure the psychophysical and eye-movement responses to drifting plaids in a direction-discrimination task. Correlation between the noise in the eye movements and percepts would suggest a shared neural substrate. Three observers were asked to track a plaid (Type I 90 deg; TF = 4 Hz, SF = 0.6 c/d; direction = -2, 0, or 2 deg), and to respond whether the motion was to the right or left of vertical. The eye-movement direction is computed from the initial 300 ms of saccade-free tracking (near open-loop). On each trial, we use the eye-movement direction to predict the perceptual response. We then compute the probability of successfully predicting the observer's response. We also use SOC analysis as an alternate measure of the correlation. We compare the data from both these analyses to the predictions of two models in which the eye movements and the percept are driven by either a common noisy signal (correlated model) or by two separate noisy signals (uncorrelated model). We also allow for the fact that our measured eye movements are degraded by eye-tracker noise. This noise causes our measured correlation to be lower than the actual biological correlation. The correlations in our data are higher than those predicted by the uncorrelated model, and are similar to the predictions of the correlated model. The proportion of perceptual responses correctly predicted by the eye movements were 0.66, 0.60, 0.73 for the -2, 0, 2 deg stimuli respectively (correlated model 0.65, 0.60, 0.70; uncorrelated model 0.58, 0.51, 0.60).The SOC proportions were 0.71, 0.64, 0.72 (correlated model 0.66, 0.64, 0.69; uncorrelated model 0.5, 0.5, 0.5). These results show that the oculomotor and perceptual system share a performance-limiting noise source and provide strong evidence that a common neural mechanism (perhaps MT or MST) drives both perception and smooth eye movements.

Beutter, Brent R.↗
NASA NTRS1995

Analysis of the Trial-By-Trial Correlation Between Eye Movement and Perceptual Responses to Moving Plaids

We have previously shown that windowing a drifting plaid with an asymmetric spatial Gaussian produces systematic biases of similar magnitude in both the perceived direction of motion and the direction of the eye movement response. To further investigate this, we simultaneously measured the pyschophysical and eye-movement responses (with an ISCAN RK426 IR tracker)to drifting plaids in a direction discrimination task. Three observers were instructed to track a plaid (Type I 90 deg.; TF = 4 Hz, SF = 0.6 c/d; windowed by a circular spatial gaussian) and to respond whether the motion was to the right or left of pure vertical. Three plaid directions were presented (-2, 0, 2 deg. with respect to straight down), so there was uncertainty in the perceptual judgements. This enabled us to examine the trial-by-trial relationship between the eye movements and psychophysical responses. The eye-movement direction was computed to be the slope of the best fitting line to the initial 300 ms of saccade-free tracking (near open-loop). Again, we found the mean psychophysical and oculomotor responses were correlated. The mean percentages of rightward responses were 6, 27, 87%, and the mean normalized eye-movement directions were -1.5, 0, and 1.0 deg. for the -2, 0, and 2 deg. stimuli respectively. We also computed the trial-by-trial correlation by performing an SOC analysis. The mean correlations were 0.52, 0.66, and 0.67 for our three observers. Because of eye-tracker measurement noise, the above results are lower limits on the actual correlation. These results support the view that the oculomotor and perceptual system share common motion inputs.

Beutter, Brent R.↗
NASA NTRS1995

Pros and Cons of Using Water Immersion to Simulate Physiological Responses to Microgravity

Head-out water immersion (HOI) has been employed as a remedial treatment for various ills and ailments for many millennia, and total body immersion even longer as protective encapsulation for the mammalian fetus. Two discrete differences between stimuli induced by true microgravity (10(exp -4) g) and HOI are readily apparent. External water pressure on the skin and accompanying negative pressure breathing cause blood to shift headward. Secondly, the gravitational force is ever present during immersion and microgravity, but its effect is essentially neutralized during Earth orbital flight. Thus, the physiological responses to immersion should not be expected to match those during microgravity. Immersion has been used mainly to study and understand kidney function and associated cardiovascular responses for control of body fluid volume and osmotic content, with some application to and simulation of microgravity responses. There is a plethora of data from human HOI studies, but relatively few controlled data from microgravity studies. In general, it appears that physiological responses occur more quickly with water immersion than in microgravity, but this may be due to less rigorous control (voluntary and involuntary) of the preflight state of crew members. The central venous pressure-vasopressin (Gauer-Henry) reflex control for fluid balance may not be of prime importance in microgravity. Gross functions such as reduced body weight and water, level of hypovolemia, decreased isokinetic strength, and lower nitrogen balance found during immersion are qualitatively similar in microgravity, but the mechanisms controlling these and other functions are, for the most part, unclear. Only acquisition of data from well-controlled microgravity experiments will resolve this discrepancy.

Greenleaf, J. E.↗
NASA NTRS1995

Reflexive OKN is Biased Like Perception

The classic "barber-pole illusion" demonstrates how the perceived motion of an ambiguous stimulus is influenced by the shape of the viewing aperture: the motion is preferentially seen in the direction of the long axis of the aperture. We have previously reported (ARVO 94) that we are able to continuously vary the strength of this effect by varying the aspect ratio of the window. In the present study we examined the motion of the eyes while subjects viewed such stimuli in an attempt to discover whether the eye movement control system performs the same computation underlying the perceptual judgments.

Mulligan, Jeffrey B.↗
NASA NTRS1996

Effect of Spaceflight on Vestibulo-Ocular Reflexes (VORS) During Angular Head Motion

Vestibulo-ocular reflexes (VORs) stabilize the eyes during head motion. During Earth-horizontal (E-H) pitch or roll rotations, canal and otolith stimuli occur together. In Earth-vertical (E-V) pitch or roll rotations, only canal signals occur. In cats and squirrel monkeys, pitch/roll VOR gains during E-H motion have been shown to be larger than during E-V motion, implying that otolith modulation plays a role in producing angular VORs (aVORs). The present experiments replicated this experiment in rhesus monkeys, and examined how spaceflight affected AVOR gain. During yaw, pitch and roll (0.5 - 1.0 Hz, 40-50 deg/s pk) motion, 3-d eye movements were recorded in four Rhesus monkeys using scleral search coils. Mean E-H and E-V pitch VOR gains were 0.85 and 0.71. Torsional VOR gains during E-H and E-V were 0.47 and 0.39. Gains are more compensatory during E-H pitch or roll. Two of the four monkeys flew for 11 days on the COSMOS 2229 Biosatellite. E-H pitch VOR gains were attenuated immediately (72 hrs) post-flight, with similar values to pre-flight E-V pitch gains. Horizontal yaw VOR gains were similar pre- and post-flight.

Tomko, David L.↗
NASA NTRS1996

Does Involuntary Attentional Capture Curtail Stimulus Processing

Under certain conditions uninformative visual cues at non-target locations increase target RTs. The typical explanation is that visual attention has been involuntarily summoned to the cued location and is unavailable when needed at the target location. Here we present evidence that capture has not just oriented attention away from the target location, but has lead to the processing of stimuli at the location of the uninformative cue.

Remington, Roger W.↗