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The use of the dynamic EKG study as a part of periodic health examination is considered to be a valuable complement to other forms of stress testing with its ability to detect abnormal heart responses to stress stimuli. It is believed that statistical correlations of dynamic EKG findings with physical examination results contribute greatly to the understanding of cardiac abnormalities.
In the case of human bone marrow, the largest number of mitoses is seen in the evening in diurnally active men, mitotic activity being at a minimum in the morning. The opposite pattern is observed for nocturnal animals such as rats and mice on a regimen of light during the daytime alternating with darkness during the night hours. The entirety of these rhythms plays an important role in the organism's responses to environmental stimuli, including its resistance to potentially harmful agents. Conditions under which circadian rhythms can be observed and validated by inferential statistical means are discussed while emphasizing how artifacts of the laboratory environment can be shown to obscure circadian periodic variations in radiosensitivity.
Four subjects compared successively presented pairs of line patterns for a match between any lines in the pattern (similarity) and for a match between all lines (identity). The encoding or study times for pattern recognition from immediate memory and the latency in responses to comparison stimuli were examined. Qualitative differences within and between subjects were most evident in study times.
Contingent negative variations in the presence and amplitudes of brain potentials evoked by sound are considered. Evidence is produced that the evoked brain stem response to auditory stimuli is clearly related to brain events associated with cognitive processing of acoustic signals since their properties depend upon where the listener directs his attention, whether the signal is an expected event or a surprise, and when sound that is listened-for is heard at last.
The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.
Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.
Tisserand's frame represents a frame in which the deformations in elastic members and the motions in a central rigid body add zero translational and angular momenta to the overall momentum of the vehicle. The considered relations have been known for some time in the case of nongyroscopic spacecraft. The present investigation is concerned with an extension of the relations to gyroscopic systems, taking into account an entirely elastic spacecraft with significant stored angular momentum. A two-dimensional free, rectangular, elastic structure with axisymmetric rotors is considered. Equations of motion are obtained with the aid of the Newton-Eulerian technique and Hamilton's principle. An analysis is conducted of the dynamics of an elastic gyroscopic free vehicle, and the dynamics of the Tisserand's frame in response to external stimuli is examined.
In the overall aim for a better understanding of the vestibular and optokinetic systems and their roles in space motion sickness, the eye movement responses to various dynamic stimuli are measured. The vestibulo-ocular reflex (VOR) and the optokinetic response, as the eye movement responses are known, consist of slow phase and fast phase nystagmus. The specific objective is to develop software programs necessary to characterize the vestibulo-ocular and optokinetic responses by distinguishing between the two phases of nystagmus. The overall program is to handle large volumes of highly variable data with minimum operator interaction. The programs include digital filters, differentiation, identification of fast phases, and reconstruction of the slow phase with a least squares fit such that sinusoidal or psuedorandom data may be processed with accurate results. The resultant waveform, slow phase velocity eye movements, serves as input data to the spectral analysis programs previously developed for NASA to analyze nystagmus responses to pseudorandom angular velocity inputs.
The fundamental principles of the adaptive structures concept and its applications to current and planned space missions are reviewed and illustrated with diagrams, drawings, graphs, and photographs. An adaptive structure is defined as one which can be modified to meet mission requirements, either by remote commands or automatically in response to external stimuli. Topics addressed include the need for adaptive structures, analytical models, ground testing, sensor/actuator-structure interactions, structural concepts, active damping, wave propagation in large structures, the selection of active member locations, and on-orbit system identification. Particular attention is given to adaptive structures being developed for the NASA Large Deployable Reflector and Optical Interferometer projects.
Computational support of the engineering design process routinely requires mathematical models of behavior to inform designers of the system response to external stimuli. However, designers also need to know the effect of the changes in design variable values on the system behavior. For large engineering systems, the conventional way of evaluating these effects by repetitive simulation of behavior for perturbed variables is impractical because of excessive cost and inadequate accuracy. An alternative is described based on recently developed system sensitivity analysis that is combined with extrapolation to form a model of design. This design model is complementary to the model of behavior and capable of direct simulation of the effects of design variable changes.
Computational support for engineering design process reveals behavior of designed system in response to external stimuli; and finds out how behavior modified by changing physical attributes of system. System-sensitivity analysis combined with extrapolation forms model of design complementary to model of behavior, capable of direct simulation of effects of changes in design variables. Algorithms developed for this method applicable to design of large engineering systems, especially those consisting of several subsystems involving many disciplines.
The paper discusses NASA High Performance Computing Initiative (HPCI), an essential component of the Federal High Performance Computing Program. The HPCI program is designed to provide a thousandfold increase in computing performance, and apply the technologies to NASA 'Grand Challenges'. The Grand Challenges chosen include integrated multidisciplinary simulations and design optimizations of aerospace vehicles throughout the mission profiles; the multidisciplinary modeling and data analysis of the earth and space science physical phenomena; and the spaceborne control of automated systems, handling, and analysis of sensor data and real-time response to sensor stimuli.
The study of intact organisms has provided biologists with a good working knowledge of most of the common organisms that have evolved in the 1 g environment of Earth. Reasonably accurate predictions can be made about organismal responses to most stimuli on Earth. To extend this knowledge to life without gravity, we must have access to the space environment for prolonged periods. Space Station Freedom will provide a facility with which to begin this type of research. Spaceflight research to date has been limited to relatively short-term exposures that have been informative but incomplete. This paper provides a brief background of known changes that have occurred in intact organisms in the space environment and proposes the kinds of experiments that are needed to expand our knowledge of life on Earth and in space.
In January 1992, the NASA Suttle mission STS 42 carried a facility designed to perform experiments on plant gravi- and photo-tropic responses. This equipment, the Gravitational Plant Physiology Facility (GPPF) was made up of a number of interconnected units mounted within a Spacelab double rack. The details of these units and the plant growth containers designed for use in GPPF are described. The equipment functioned well during the mission and returned a substantial body of time-lapse video data on plant responses to tropistic stimuli under conditions of orbital microgravity. GPPF is maintained by NASA Ames Research Center, and is flight qualifiable for future spacelab missions.
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.
One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.
Recently, we have shown that shear stress stimulates NO(*) production by the protein kinase B/Akt (Akt)-dependent mechanisms in bovine aortic endothelial cells (BAEC) (Go, Y. M., Boo, Y. C., Park, H., Maland, M. C., Patel, R., Pritchard, K. A., Jr., Fujio, Y., Walsh, K., Darley-Usmar, V., and Jo, H. (2001) J. Appl. Physiol. 91, 1574-1581). Akt has been believed to regulate shear-dependent production of NO(*) by directly phosphorylating endothelial nitric-oxide synthase (eNOS) at the Ser(1179) residue (eNOS-S(1179)), but a critical evaluation using specific inhibitors or dominant negative mutants (Akt(AA) or Akt(AAA)) has not been reported. In addition, other kinases, including protein kinase A (PKA) and AMP kinase have also shown to phosphorylate eNOS-S(1179). Here, we show that shear-dependent phosphorylation of eNOS-S(1179) is mediated by an Akt-independent, but a PKA-dependent, mechanism. Expression of Akt(AA) or Akt(AAA) in BAEC by using recombinant adenoviral constructs inhibited phosphorylation of eNOS-S(1179) if cells were stimulated by vascular endothelial growth factor (VEGF), but not by shear stress. As shown before, expression of Akt(AA) inhibited shear-dependent NO(*) production, suggesting that Akt is still an important regulator in NO production. Further studies showed that a selective inhibitor of PKA, H89, inhibited shear-dependent phosphorylation of eNOS-S(1179) and NO(*) production. In contrast, H89 did not inhibit phosphorylation of eNOS-S(1179) induced by expressing a constitutively active Akt mutant (Akt(Myr)) in BAEC, showing that the inhibitor did not affect the Akt pathway. 8-Bromo-cAMP alone phosphorylated eNOS-S(1179) within 5 min without activating Akt, in an H89-sensitive manner. Collectively, these results demonstrate that shear stimulates phosphorylation of eNOS-S(1179) in a PKA-dependent, but Aktindependent manner, whereas the NO(*) production is regulated by the mechanisms dependent on both PKA and Akt. A coordinated interaction between Akt and PKA may be an important mechanism by which eNOS activity is regulated in response to physiological stimuli such as shear stress.
One physiologic consequence of extended periods of weightlessness is the rapid loss of bone mass associated with skeletal unloading. Conversely, mechanical loading has been shown to increase bone formation and stimulate osteoblastic function. The mechanisms underlying mechanotransduction, or how the osteoblast senses and converts biophysical stimuli into cellular responses has yet to be determined. For non-innervated mechanosensitive cells like the osteoblast, mechanotransduction can be divided into four distinct phases: 1) mechanocoupling, or the characteristics of the mechanical force applied to the osteoblast, 2) biochemical coupling, or the mechanism through which mechanical strain is transduced into a cellular biochemical signal, 3) transmission of signal from sensor to effector cell and 4) the effector cell response. This review examines the characteristics of the mechanical strain encountered by osteoblasts, possible biochemical coupling mechanisms, and how the osteoblast responds to mechanical strain. Differences in osteoblastic responses to mechanical strain are discussed in relation to the types of strain encountered and the possible transduction pathways involved.