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NASA NTRS1999

Quantitative Method of Measuring Metastatic Activity

The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated uroldnase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

Morrison, Dennis R.↗
NASA NTRS1999

Environmental and Archaeological Research in the Peten, Guatemala

The Peten, Northern Guatemala, was once inhabited by a population of several million Maya before their collapse in the 9th century A.D.. The seventh and eight centuries were a time of crowning glory four millions of Maya; by 930 A.D. only a few scattered houses remained, testifying to the greatest disaster in human history. What is known is that at the time of their collapse the Maya had cut down most of their trees. After centuries of regeneration the Peten now represent the largest remaining tropical forest in Central America but is experiencing rapid deforestation in the wake of an invasion of settlers. The successful adaptive techniques of the indigenous population are being abandoned in favor of the destructive techniques of monoculture and cattle raising. Remote sensing and Geographic Information System (GIS) analysis are being used to address issues in Maya archeology as well as monitor the effects of increasing deforestation in the area today. One thousand years ago the forests of the Peten were nearly destroyed by the ancient Maya who after centuries of successful adaptation finally overused their resources. Current inhabitants are threatening to do the same thing today in a shorter time period with a lesser population. Through the use of remote sensing/GIS analysis we are attempting to answer questions about the past in order to protect the resources of the future.

Sever, Thomas L.↗
NASA NTRS1999

A Photometric Technique for Determining Fluid Concentration using Consumer-Grade Hardware

In support of a separate study to produce an exponential concentration gradient in a magnetic fluid, a noninvasive technique for determining, species concentration from off-the-shelf hardware has been developed. The approach uses a backlighted fluid test cell photographed with a commercial digital camcorder. Because the light extinction coefficient is wavelength dependent, tests were conducted to determine the best filter color to use, although some guidance was also provided using an absorption spectrophotometer. With the appropriate filter in place, the provide attenuation of the light passing, through the test cell was captured by the camcorder. The digital image was analyzed for intensity using, software from Scion Image Corp. downloaded from the Internet. The analysis provides a two-dimensional array of concentration with an average error of 0.0095 ml/ml. This technique is superior to invasive techniques, which require extraction of a sample that disturbs the concentration distribution in the test cell. Refinements of this technique using a true monochromatic laser light Source are also discussed.

Leslie, F.↗
NASA NTRS1999

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and their Implications for Bone Strain

Effective countermeasures to prevent loss of bone mineral during long duration space flight remain elusive. Despite an exercise program on MIR flights, the data from LeBlanc et al. (1996) indicated that there was still a mean rate of loss of bone mineral density in the proximal femur of 1.58% per month (n=18, flight duration 4 - 14.4 months). The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. A plausible hypothesis is that bone loss during space flight, such as that reported by LeBlanc et al. (1996), may result from failure to effectively load the skeleton in order to generate localized bone strains of sufficient magnitude to prevent disuse osteoporosis. A variety of methods have been proposed to simulate locomotor exercise in reduced gravity. In such simulations, and in an actual microgravity environment, a gravity replacement load (GRL) must always be added to return the exercising subject to the support surface and the resulting skeletal load is critically dependent upon the magnitude of the GRL. To our knowledge, GRLs during orbital flight have only been measured once (on STS 81) and it is likely that most or all prior treadmill exercise in space has used GRLs that were less than one body weight. McCrory (1997) has shown that subjects walking and running in simulated zero-G can tolerate GRLs of 1 if an appropriate harness is used. Several investigators have attempted to measure in vivo strains and forces in the bones of humans, but have faced ethical and technical limitations. The anteromedial aspect of the tibial midshaft has been a common site for the placement of strain gauges; one reason to measure strains in the anterior tibia is that this region is surgically accessible. Aamodt et al. (1997) were able to measure strains on the lateral surface of the proximal femur only because their experimental subjects were already scheduled for hip surgery. Lu et al. (1997) used an instrumented massive proximal femoral prosthesis along with electromyographic measurements to demonstrate that femoral forces depend on muscular activity. These analyses of in vivo bone mechanics are valuable. The invasive nature of the procedures involved, however, limits both the number of subjects and the number of strain gauge locations. Further, the results of these studies may be confounded by the inclusion of subjects with pathological conditions. Gross et al. (1992) measured strain at three locations on the equine third metacarpal and used those data to construct a computer model of the internal strain environment of the bone. An analogous placement of multiple gauges in living humans would be difficult and potentially hazardous because of the depth of soft tissue overlying the tibia and femur.

Peterman, M.↗
NASA NTRS1999

Expression of Novel Gene Products Upregulated by Disuse is Normalized by an Osteogenic Mechanical Stimulus: Evidence for the Molecular Basis of a Low Level Biomechanical Countermeasure for Osteoporosis?

The National Research Council's report entitled: A Strategy for Space Biology and Medical Science, highlighted several areas of fundamental scientific investigation which must be addressed to make long-term space exploration not only feasible, but safe. This "Goldberg Strategy," as well as several subsequent reports published by the NRC's Space Studies Board (e.g., Assessment of Programs in Space Biology and Medicine, Smith et. al., 1991), suggests that the principal hurdle to man's extended presence in space is the osteopenia which parallels reduced gravity. Ironically, the most significant risk to the skeleton may only be realized on return to normal gravitational fields, and full recovery of bone mass may never occur. Effective counter-measures to this microgravity induced bone loss are thus essential. Considering the similarities of space and aging induced osteopenia, an indisputable benefit of such a prophylaxis would be its potential as a treatment for the bone loss which plagues over 25 million people in the U.S. The osteogenic potential of mechanical strain is strongly frequency dependent, with sensitivity increasing up through at least 60 Hz (cycles per second). One hundred seconds per day of a 1 Hz cyclic loading will inhibit disuse osteopenia only if sufficient in magnitude to engender 1000 microstrain (mu(epsilon)) in the tissue. When loading is applied at 30 Hz, however, mechanical strains on the order of 5O mu(epsilon) (approx. 1% of the peak strains which occur in bone during vigorous functional activity), can stimulate bone formation in a duration dependent manner. In longer term animal studies, strains of less than 10 mu(epsilon), induced non-invasively via a whole body vibration, will stimulate bone formation on the surfaces of trabeculae, increase bone density, and improve strength. Finally, preliminary results from a double blind prospective clinical trial shows promise in inhibiting the bone loss which parallels the menopause. Based on these observations, we propose that these high frequency, low magnitude, mechanical strains effectively serve as a "surrogate" for musculoskeletal ground reaction forces, and thus represent an ideal countermeasure to the osteopenia which parallels microgravity conditions. The specific goal of this NASA funded work is to identify genes in bone upregulated by disuse, and to determine the efficacy of an osteogenic mechanical stimulus to downregulate their expression.

Rubin, C.↗
NASA NTRS1999

Salivary Pharmacodynamics and Bioavailability of Promethazine in Human Subjects

The acute effects of exposure to microgravity include the development of space motion sickness which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), has side effects which include nausea, drowsiness, dizziness, sedation and impaired psychomotor performance. In a ground-based study with commercial airline pilots and shuttle simulator trainers, we measured sleep and psychomotor performance variables, and physiological variables such as blood pressure and heart rate, as a function of circulating drug concentrations in the body. We evaluated a non-invasive sampling method (saliva) as a means of assessing pharmacodynamics following a single intramuscular (IM) dose of PMZ.

Putcha, Lakshmi↗
NASA NTRS1999

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Cohen, Richard↗
NASA NTRS1999

Alterations in Cardiovascular Regulation and Function During Long-Term Simulated Microgravity

The Cardiovascular Alterations Team is conducting studies of hemodynamic regulation and susceptibility to arrhythmias resulting from sixteen days of simulated microgravity exposure. In these studies very intensive measurements are made during a short duration of bed rest. In this collaborative effort are making many of the same measurements, however much less frequently, on subjects who are exposed to a much longer duration of simulated microgravity. Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In addition, numerous reports from the past 30 years suggest that the incidence of ventricular arrhythmias among astronauts is increased during space flight. However, the effects of space flight and the associated physiologic stresses on cardiac conduction processes are not known, and an increase in cardiac susceptibility to arrhythmias has never been quantified. In this project we are applying the most powerful technologies available to determine, in a ground-based study of long duration space flight, the mechanisms by which space flight affects cardiovascular function, and then on the basis of an understanding of these mechanisms to develop rational and specific countermeasures. To this end we are conducting a collaborative project with the Bone Demineralization/Calcium Metabolism Team of the National Space Biomedical Research Institute (NSBRI). The Bone Team is conducting bed rest studies in human subjects lasting 17 weeks, which provides a unique opportunity to study the effects of long duration microgravity exposure on the human cardiovascular system. We are applying a number of powerful new methods to these long term bed rest subjects, including cardiovascular system identification (CSI), microvolt level T wave alternans analysis, and cardiac magnetic resonance imaging to assess non-invasively the effects of simulated long duration space flight on the cardiovascular system.

Cohen, Richard J.↗
NASA NTRS1998

Behavior and Performance Project

Behavior is an overt manifestation of underlying biology. As such, alterations in biological systems that result from spaceflight would be expected to evidence themselves in subtle or even pronounced changes in the behavior of that organism. These alterations in visible behavior may then indicate or even be diagnostic of alterations in the physical well-being of humans and other animals as they adapt to space environments or readapt to Earth--alterations that might not otherwise be detected without relatively invasive and frequently expensive procedures. Moreover, behavior and performance constitute the central standard for evaluating the mission success of spaceflight ventures. The success or failure of any excursion into space is primarily indexed by the ability of astronauts and cosmonauts to perform the tasks and experiments of any particular mission, to land a re-entry vehicle after extended exposure to microgravity (as with the space shuttle), or to make time-critical and life-saving repairs or other decisions while in orbit (as with the recent Mir events). Thus, understanding the effects spaceflight on behavior and performance is inherently important, in addition to those insights that behavior can provide about the physiological consequences of space adaptation.

Washburn, David A.↗
NASA NTRS2000

Archaeological and Environmental Research of the Peten, Guatemala, Using Remote Sensing/GIS Research

The Peten, northern Guatemala, was once inhabited by a population of several million Maya before their collapse in the 9th century AD. Although the seventh and eight centuries were a time of crowning glory for millions of Maya; by 930 A.D. only a few scattered houses remained. What is known, is that at the time of their collapse, the Maya had cut down most of their trees. After centuries of regeneration the Peten now represent the largest remaining tropical forest in Central America but is experiencing rapid deforestation in the wake of an invasion of settlers. The successful adaptive techniques of the indigenous population are being abandoned in favor of the destructive techniques of monoculture and cattle raising. These techniques also contribute to the destruction and looting of unrecorded archeological sites. Remote sensing and GIS analysis are being used to address issues in Maya archeology as well as monitor the effects of increasing deforestation in the area today. One thousand years ago the forests of the Peten were nearly destroyed by the ancient Maya, who, after centuries of successful adaptation, finally overused their resources. Current inhabitants are threatening to do the same thing today in a shorter time period with a lesser population. Through the use of remote sensing/GIS analysis we are attempting to answer questions about the past in order to protect the resources of the future.

Sever, Thomas L.↗
NASA NTRS1985

Ultrasound Techniques for Space Applications

Ultrasound has proven to be a safe non-invasive technique for imaging organs and measuring cardiovascular function. It has unique advantages for application to problems with man in space including evaluation of cardiovascular function both in serial studies and during critical operations. In addition, specialized instrumentation may be capable of detecting the onset of decompression sickness during EVA activities. A spatial location and three-dimensional reconstruction system is being developed to improve the accuracy and reproducibility for serial comparative ultrasound studies of cardiovascular function. The three-dimensional method permits the acquisition of ultrasonic images from many views that can be recombined into a single reconstruction of the heart or vasculature. In addition to conventional imaging and monitoring systems, it is sometimes necessary or desirable to develop instrumentation for special purposes. One example of this type of development is the design of a pulsed-Doppler system to monitor cerebral blood flow during critical operations such as re-entry. A second example is the design of a swept-frequency ultrasound system for the detection of bubbles in the circulatory system and/or soft tissues as an early indication of the onset of decompression sickness during EVA activities. This system exploits the resonant properties of bubbles and can detect both fundamental and second harmonic emissions from the insonified region.

Rooney, James A.↗
NASA NTRS1998

An Evanescent Microwave Probe for Super-Resolution Nondestructive Imaging of Metals, Semiconductors, Dielectrics, Composites and Biological Specimens

Using evanescent microwaves with decay lengths determined by a combination of microwave wavelength (lambda) and waveguide termination geometry, we have imaged and mapped material non-uniformities and defects with a resolving capability of lambda/3800=79 microns at 1 GHz. In our method a microstrip quarter wavelength resonator was used to generate evanescent microwaves. We imaged materials with a wide range of conductivities. Carbon composites, dielectrics (Duroid, polymers), semiconductors (3C-SiC, polysilicon, natural diamond), metals (tungsten alloys, copper, zinc, steel), high-temperature superconductors, and botanical samples were scanned for defects, residual stresses, integrity of brazed junctions, subsurface features, areas of different film thickness and moisture content. The evanescent microwave probe is a versatile tool and it can be used to perform very fast, large scale mapping of a wide range of materials. This method of characterization compares favorably with ultrasound testing, which has a resolution of about 0.1 mm and suffers from high absorption in composite materials and poor transmission across boundaries. Eddy current methods which can have a resolution on the order of 50 microns are restricted to evaluating conducting materials. Evanescent microwave imaging, with careful choice of operating frequency and probe geometry, can have a resolution of up to 1 micron. In this method we can scan hot and moving objects, sample preparation is not required, testing is non-destructive, non-invasive and non-contact, and can be done in air, in liquid or in vacuum.

Pathak, P. S.↗
NASA NTRS1999

Adventures in Space Medicine

Human space flight experience has demonstrated a variety of hazards and risks to health and performance. In developing ways to help respond to these issues, the field of space medicine has developed a comprehensive program of space flight health risk management that has resulted in positive contributions to medicine and society in general. Examples include accelerated focus on critical health issues such as aging and osteoporosis, and development of new technologies such as non-invasive diagnostic testing for diabetics. The role of health care professionals in human space exploration represents a fulfillment of new adventures and expanding frontiers.

Billica, Roger D.↗
NASA NTRS1999

MRI Measurements and Granular Dynamics Simulation of Segregation of Granular Mixture

A counter intuitive axial segregation phenomenon in a rotating horizontal cylinder has recently captured attention of many researchers in different disciplines. There is a growing consensus that the interplay between the particle dynamics and the evolution of the internal structure during the segregation process must be carefully investigated. Magnetic resonance imaging (MRI) has been used to non-invasively obtain much needed dynamic/static information such as velocity and concentration profiles, and it has proven to be capable of depicting the evolution of segregation processes. Segregation in a rotating cylinder involves two processes: the first is to transport small particles in the radial direction to form a radial core, and the second is to transform the radial core into axially segregated bands. Percolation and/or "stopping" have been proposed as mechanisms for the radial segregation. As to mechanisms for axial band formation, much less is known. The difference in the dynamic angle of repose has been proposed to segregate different components in the axial direction. Recently, Hill and Kakalios have reported that particles mix or demix depending upon the competition between diffusion and preferential drift whose order can be determined by the dynamic angle of repose through the adjustment of the rotation rate. We claim that the dynamic angle of repose could be one of the causes, however, it fails to offer reasonable explanations for certain aspects of the axial migration. For example, we always observe that the radial segregation precedes the axial segregation and small particles migrate in the radial direction to form an axially extended radial core. It then transforms into axially segregated bands. By definition, the effects of the dynamic angle of repose are restricted near the free surface where the flowing layer is present. However, during the process of transforming from the radially segregated core to axially segregated bands, small particles located in the deep core region, which is untouched by the flowing layer, also completely disappear. Usually, the dynamics angle of repose are uniquely defined for individual species to characterize particle properties, and the dynamic angle of repose thus defined provides little information for the dynamic angle of repose of the mixture since the concentration ratio and the internal packing structure do not remain the same during the segregation processes. Under microgravity environment, the dynamics angle of repose argument does not hold since there is simply no flowing layer to influence/determine the preferred directions of segregation. We have thus designed an experiment so that the effects of the dynamic angle of repose can be minimized by filling the cylinder almost completely full. Small particles still formed a radial core and also migrated to form axial bands. As ground based experiments we have designed and conducted both 2D and 3D segregation experiments. The 2D experiments are performed using a thin cylinder (the gap between two end caps is about 5 mm) filled with different combinations of particles. The 3D experiments are conducted with a long cylinder of its length and diameter of 27cm and 7cm, respectively. Results of 2D experiments indicate that different mechanisms govern particle motion in regions near and far from the axis of rotation. Results of 3D experiments indicate that a series of collapses of microstructures of particle packing (micro-collapses) may be responsible for the creation of voids for small particles to migrate through in the axial direction. We have successfully eliminated the dynamic angle of repose as a cause for segregation, however, by almost completely filling the cylinder with the particles, we have lost an opportunity to investigate a possibility of particle "mobility" being a cause for segregation which requires a flowing surface but not the difference in the angle of repose. This is currently being investigated.

Nakagawa, M.↗
NASA NTRS1999

Noninvasive Intracranial Volume and Pressure Measurements Using Ultrasound (Head and Spinal)

Prevention of secondary brain injuries following head trauma can be accomplished most easily when intracranial pressure (ICP) is monitored. However, current measurement techniques are invasive and thus not practical in the combat environment. The Pulsed Phase Lock Loop device, which was developed and patented by consultants Drs. Yost and Cantrell, uses a unique, noninvasive ultrasonic phase comparison method to measure slight changes in cranial volume which occur with changes in ICP. Year two studies included whole body head-up and head-down tilting effects on intracranial compliance and pressure in six healthy volunteers.

Hargens, Alan R.↗
NASA NTRS2001

Three Dimensional Cross-Sectional Properties From Bone Densitometry

Bone densitometry has previously been used to obtain cross-sectional properties of bone in a single scan plane. Using three non-coplanar scans, we have extended the method to obtain the principal area Moments of inertia and orientations of the principal axes at each cross-section along the length of the scan. Various 5 aluminum phantoms were used to examine scanner characteristics to develop the highest accuracy possible for in vitro non-invasive analysis of mass distribution. Factors considered included X-ray photon energy, initial scan orientation, the included angle of the 3 scans, and Imin/Imax ratios. Principal moments of inertia were accurate to within 3.1% and principal angles were within 1 deg. of the expected value for phantoms scanned with included angles of 60 deg. and 90 deg. at the higher X-ray photon energy. Low standard deviations in error also 10 indicate high precision of calculated measurements with these included angles. Accuracy and precision decreased slightly when the included angle was reduced to 30 deg. The method was then successfully applied to a pair of excised cadaveric tibiae. The accuracy and insensitivity of the algorithms to cross-sectional shape and changing isotropy (Imin/Imax) values when various included angles are used make this technique viable for future in vivo studies.

Cleek, Tammy M.↗
NASA NTRS2001

User Acceptability of Physiological and Other Measures of Hazardous States of Awareness

Two studies explored user acceptance of devices that measure hazardous states of awareness. In the first study, critical incident data were collected in two workshops from 11 operators working as air traffic controllers or commercial pilots. These critical incident data were used to develop a survey of the acceptability of awareness measures. In the second study, the survey was administered to 100 people also working as air traffic controllers or commercial pilots. Results show that operators are open to the inclusion of technology to measure HSAs even if that technology is somewhat invasive as long as feedback about the HSAs is considered to be useful and helpful. Nonetheless, a major concern is the legal complications associated with being recorded, particularly for older and more experienced operators. Air traffic controllers emphasized the importance of sharing technology information with supervisors in order to receive backup or assistance under conditions of task overload, whereas pilots emphasized the influence of work schedules on problems with awareness. Recommendations are offered concerning the implementation of devices to measure hazardous states of awareness.

Dickinson, Terry L.↗
NASA NTRS2000

SPINOFF 2000

For the past 42 years, NASA has made special efforts to ensure the widest possible dissemination of its research and technology developments. We share the wealth of technology developed for our missions with the nation's industries to contribute to US economic strength and quality of life. For the past 27 years, this publication has provided you with over 1,200 examples of products and services developed as a direct result of commercial partnerships between NASA and the business community. Examples have covered products from fire retardant materials and air pollution monitors to non-invasive cardiac monitors and sensors for environmental control. In the Technology Transfer and Outreach section of Spinoff 2000, we highlight the activities of our Ames Research Center's Commercial Technology Office (CTO). Their efforts to facilitate and support technology commercialization are representative of the CTO at each field center. Increased activities to accelerate the dissemination of technologies, speed up the process of patent licensing, quicken the release of software for beta testing, support and manage incubators, and hasten the collaboration with commercial and academic organizations will continue to maximize the earliest potential commercial utilization of NASA's new inventions and technologies. Spinoff 2000 is organized into three sections: (1) Aerospace and Development highlights major research and development efforts currently carried out at the 10 NASA field centers; (2) Commercial Benefits-Spinoffs describes commercially available products and services resulting from the transfer of NASA technology; and (3) Technology Transfer and Outreach features this year's center spotlight, NASA's Ames Research Center, and its commercialization efforts, as well as the mechanisms in place nationwide to assist US industry in obtaining, transferring, and applying NASA technology, expertise, and assistance.

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