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DOE OSTI2025

Brachypodium SPEECHLESS2 Promoter Drives Expression of a Synthetic EPF to Reduce Stomatal Density in Sugarcane Without Pleiotropic Effects

Stomata are microscopic pores that regulate the exchange of CO 2 and water vapour, making them a major target for engineering plants with improved intrinsic water use efficiency (iWUE). Proof-of-concept studies have demonstrated the potential to increase iWUE by reducing stomatal density (SD) and stomatal conductance (g sw ) by ubiquitously expressing EPIDERMAL PATTERNING FACTOR (EPF) family genes. However, unwanted effects on leaf, stem and reproductive traits are often observed when EPFs are misexpressed in this fashion. We sought to test if these effects result from pleiotropy and to identify a targeted promoter that can circumvent the side effects while retaining the desired reduction in SD. A previously reported synthetic EPF (EPF syn ) was expressed in sugarcane ( Saccharum spp.) using two putatively tissue-specific promoters from Brachypodium distachyon (BdCESA7p and BdSPCH2p) and a ubiquitous control from Zea mays (ZmUBI4p). BdSPCH2p control reduced SD to statistically equivalent levels as ZmUBI4p on the abaxial (23%) and adaxial (23%) leaf surfaces. ZmUB4p and BdCESA7p induce expression in four tissue types often associated with pleiotropic effects in EPF-expressing low SD plants. Transgenic plants carrying either the BdCESA7p or ZmUBI4p EPF syn cassettes displayed leaf chlorosis, reduced leaf nitrogen and chlorophyll content, and altered stem architecture. However, transgenic events harboring the BdSPCH2p EPF syn cassette restricted EPF syn expression to the stomatal development zone and leaf nodal tissues and produced transgenic plants without the associated pleiotropic effects. These results represent an important step toward engineering low-SD crops since they show that targeted gene expression can engineer stomatal patterning without impairing agronomically important traits.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2014

Nuclear Thermal Propulsion Ground Test History

Nuclear Thermal Propulsion (NTP) was started in ~1955 under the Atomic Energy Commission as project Rover and was assigned to Los Alamos National Laboratory. The Nevada Test Site was selected in 1956 and facility construction began in 1957. The KIWI-A was tested on July 1, 1959 for 5 minutes at 70MW. KIWI-A1 was tested on July 8, 1960 for 6 minutes at 85MW. KIWI-A3 was tested on October 10, 1960 for 5 minutes at 100MW. The National Aeronautics and Space Administration (NASA) was formed in 1958. On August 31, 1960 the AEC and NASA established the Space Nuclear Propulsion Office and named Harold Finger as Director. Immediately following the formation of SNPO, contracts were awarded for the Reactor In Flight Test (RIFT), master plan for the Nuclear Rocket Engine Development Station (NRDS), and the Nuclear Engine for Rocket Vehicle Application (NERVA). From December 7, 1961 to November 30, 1962, the KIWI-B1A, KIWI-B1B, and KIWI-B4A were tested at test cell A. The last two engines were only tested for several seconds before noticeable failure of the fuel elements. Harold Finger called a stop to any further hot fire testing until the problem was well understood. The KIWI-B4A cold flow test showed the problem to be related to fluid dynamics of hydrogen interstitial flow causing fuel element vibrations. President Kennedy visited the NTS one week after the KIWI-B4A failure and got to see the engine starting to be disassembled in the maintenance facility. The KIWI-B4D and KIWI-B4E were modified to not have the vibration problems and were tested in test cell C. The NERVA NRX program started testing in early 1964 with NRX-A1 cold flow test series (unfueled graphite core), NRX-A2 and NRX-A3 power test series up to 1122 MW for 13 minutes. In March 1966, the NRX-EST (Engine System Test) was the first breadboard using flight functional relationship and total operating time of 116 minutes. The NRX-EST demonstrated the feasibility of a hot bleed cycle. The NRX-A5 had multiple start-ups in May-June 1966 with 30.75 minutes accumulative operating time at or above 1GW. The NRX-A6 was tested in December 1969 and ran for 62 minutes at 1100 MW. Each engine had post-test examination and found various structure anomalies which were identified for correction and the fuel element corrosion rate was reduced. The Phoebus series of research reactors began testing at test cell C, in June 1965 with Phoebus 1A. Phoebus 1A operated for 10.5 minutes at 1100 MW before unexpected loss of propellant and leading to an engine breakdown. Phoebus 1B ran for 30 minutes in February of 1967. Phoebus 2A was the highest steady state reactor built at 5GW. Phoebus 2A ran for 12 minutes at 4100 MW demonstrating sufficient power is available. The Peewee test bed reactor was tested November- December 1968 in test cell C for 40 minutes at 500MW with overall performance close to pre-run predictions. The XE' engine was the only engine tested with close to a flight configuration and fired downward into a diffuser at the Engine Test Stand (ETS) in 1969. The XE' was 1100 MW and had ~28 start-ups. The nuclear furnace NF-1 was operated at 44 MW with multiple test runs at 90 minutes in the summer of 1972. The NF-1 was the last NTP reactor tested. The Rover/NERVA program was cancelled in 1973. However, before cancellation, a lot of other engineering work was conducted by Aerojet on a 75, 000 lbf prototype flight engine and by Los Alamos on a ~16,000 lbf "Small Engine" nuclear rocket design. The ground test history of NTP at the NRDS also offers many lessons learned on how best to setup, operate, emergency shutdown, and post-test examine NTP engines. The reactor and engine maintenance and disassembly facilities were used for assembly and inspection of radioactive engines after testing. Most reactor/ engines were run at test cell A or test cell C with open air exhaust. The Rover/NERVA program became aware of a new environmental regulation that would restrict the amount of radioactive particulates allowed to be release in open air and successfully demonstrated a scrubber concept with the NF-1. The ETS stand was the only one with a high altitude test chamber used for XE'. The ETS and other test cells showed the effects the engine's radiation had on the facility materials and instrumentation as well as side effects the ground test facility has back on the engine operation. The breakdown of Phoebus 1A at test cell C showed how the site was cleaned up and back to operation for five more engines before the program was cancelled.

Gerrish, Harold P.↗

NASA NTRS2000

Dietary fat intake, supplements, and weight loss

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

NASA Discipline Musculoskeletal↗

DOE OSTI2021

Computational studies reveal Fluorine based quinolines to be potent inhibitors for proteins involved in SARS-CoV-2 assembly

World is witnessing one of the worst pandemics of this century caused by SARS-CoV-2 virus which has affected millions of individuals. Despite rapid efforts to develop vaccines and drugs for COVID-19, the disease is still not under control. Chloroquine (CQ) and Hydroxychloroquine (HCQ) are two very promising inhibitors which have shown positive effect in combating the disease in preliminary experimental studies, but their use was reduced due to severe side-effects. Here, we performed a theoretical investigation of the same by studying the binding of the molecules with SARS-COV-2 Spike protein, the complex formed by Spike and ACE2 human receptor and a human serine protease TMPRSS2 which aids in cleavage of the Spike protein to initiate the viral activation in the body. Both the molecules had shown very good docking energies in the range of -6kcal/mol. Subsequently, we did a high throughput screening for other potential quinoline candidates which could be used as inhibitors. From the large pool of ligand candidates, we shortlisted the top three ligands (binding energy -8kcal/mol). We tested the stability of the docked complexes by running Molecular Dynamics (MD) simulations where we observed the stability of the quinoline analogues with the Spike-ACE2 and TMPRSS2 nevertheless the quinolines were not stable with the Spike protein alone. Thus, although the inhibitors bond very well with the protein molecules their intrinsic binding affinity depends on the protein dynamics. Moreover, the quinolines were stable when bound to electronegative pockets of Spike-ACE2 or TMPRSS2 but not with Viral Spike protein. We also observed that a Fluoride based compound: 3-[3-(Trifluoromethyl)phenyl]quinoline helps the inhibitor to bind with both Spike-ACE2 and TMPRSS2 with equal probability. The molecular details presented in this study would be very useful for developing quinoline based drugs for COVID-19 treatment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRSDate not supplied

The Effects of Plasma Application on Radish Seeds with Implications for Space Crop Production

In extended space missions, the astronaut diet will consist mostly of prepackaged foods. This could result in nutritional deficiencies due to the gradual breakdown of certain vitamins. To address this deficiency, fresh produce must be grown from seed during spaceflight. Stored seeds, however, can be vulnerable to microbial contamination which could jeopardize plant health and crop food safety. To alleviate this concern, the current practice is to sanitize seeds on the ground before spaceflight to the International Space Station (ISS). Methods of seed sanitization include alcohol soaking and chlorine gas fumigation, which have harmful effects on the environment and human health. Plasma application is a new sanitization approach that avoids these negative side effects while potentially elevating germination rate and improving growth rate; yet plasma application requires specific exposure time, power, and pressure to achieve these benefits. In the present study, Raphanus sativus ‘Cherry Belle’ radish seeds were exposed to either low pressure (Diener) plasma or atmospheric pressure plasma for varying increments of time (30s-1200s). Data collected includes immediate germination rate (viability) and microbial log reduction. Additionally, seeds were stored for later germination rate testing. Microbial assay controls have highlighted variability in initial microbial load between individual seeds, and further work is being performed to determine the standard microbial load of an untreated seed. In some samples, a negative log reduction was observed after plasma treatment encouraging further study to determine if the plasma is perforating the seed coat and releasing endophytic microbes. Treatment with Diener plasma shows promising microbial log reduction, but lower viability. In contrast, treatment with atmospheric pressure plasma offers high viability, but poor microbial log reduction. Further study will aim at determining whether plasma treatment is effective at not only sanitization, but sterilization. This research was funded by a NASA grant at the Kennedy Space Center.

Plasma↗

NASA NTRSDate not supplied

The Effects of Plasma Application on Radish Seeds with Implications for Space Crop Production

Space Crop Production↗

NASA NTRS1976

Prevention of experimental motion sickness by scopolamine absorbed through the skin

A double-blind placebo-controlled study compared the efficacy of the antimotion sickness drug scopolamine when administered by oral or transdermal routes. A secondary purpose was to extend our bioassay involving fixed-dose combinations of the homergic drugs promethazine and ephedrine. After receiving 12 apparently identical drug-placebo treatments, eight normal male students were exposed in a slow rotation room to stressful accelerations generated by their execution of 40 head movements out of the plane of the room's rotation at 1 rpm and at 1-rpm increments until either symptoms were experienced (just short of frank motion sickness) or the 27-rpm ceiling on the test was reached. Efficacy of a drug was defined in terms of the placebo-range and categorized as beneficial, inconsequential, or detrimental. The only detrimental effect was with scopolamine given orally. It is concluded that the advantages of the transdermal scopolamine, which include minimal side effects and prolonged effectiveness, deserve full exploitation.

Graybiel, A.↗

DOE OSTI2026

Comparison of plasma response models for RMP effects on the divertor and scrape-off layer in KSTAR

Resonant magnetic perturbations (RMPs) are beneficial for control of edge localized modes (ELMs) in tokamaks. Nevertheless, a side effect of RMPs is the appearance of helical striations in the particle and heat loads onto divertor targets. The extent and field line connection of these striations is significantly altered by the plasma response to external perturbations. For an ELM suppressed high confinement (H-mode) plasma at KSTAR, magnetic footprints are computed by FLARE based on plasma response from GPEC, MARS-F, M3D-C1 and JOREK with substantial differences in the resulting footprints (from 2 cm to 14 cm). This is reflected in EMC3-EIRENE simulations of the resulting heat loads: it is found that either the peak value or the extent of the striations appears to be overestimated compared to infrared camera measurements. Reasonable agreement can only be achieved for the smallest footprint for lower input power and lower cross-field transport, or for higher upstream density and radiative power losses.

Frerichs, H. [Univ. of Wisconsin, Madison, WI (Uni↗

DOE OSTI2023

Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

Cardiovascular diseases (CVD), such as myocardial infarction (MI), constitute one of the world’s leading causes of annual deaths. This cardiomyopathy generates a tissue scar with poor anatomical properties and cell necrosis that can lead to heart failure. Necrotic tissue repair is required through pharmaceutical or surgical treatments to avoid such loss, which has associated adverse collateral effects. However, to recover the infarcted myocardial tissue, biopolymer-based scaffolds are used as safer alternative treatments with fewer side effects due to their biocompatibility, chemical adaptability and biodegradability. For this reason, a systematic review of the literature from the last five years on the production and application of chitosan scaffolds for the reconstructive engineering of myocardial tissue was carried out. Seventy-five records were included for review using the “preferred reporting items for systematic reviews and meta-analyses” data collection strategy. It was observed that the chitosan scaffolds have a remarkable capacity for restoring the essential functions of the heart through the mimicry of its physiological environment and with a controlled porosity that allows for the exchange of nutrients, the improvement of the electrical conductivity and the stimulation of cell differentiation of the stem cells. In addition, the chitosan scaffolds can significantly improve angiogenesis in the infarcted tissue by stimulating the production of the glycoprotein receptors of the vascular endothelial growth factor (VEGF) family. Therefore, the possible mechanisms of action of the chitosan scaffolds on cardiomyocytes and stem cells were analyzed. For all the advantages observed, it is considered that the treatment of MI with the chitosan scaffolds is promising, showing multiple advantages within the regenerative therapies of CVD.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor

Highlights: • Lenvatinib combined with radiation significantly inhibits thyroid cancer growth. • Combined therapy induced apoptosis and G2/M phase cell cycle arrest. • Irradiation increased cellular uptake of lenvatinib into cancer cells. • Combined therapy suggests a new therapeutic strategy for advanced thyroid cancer. Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5–15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2017

Machine Learning Approaches to Increasing Value of Spaceflight Omics Databases

The number of spaceflight bioscience mission opportunities is too small to allow all relevant biological and environmental parameters to be experimentally identified. Simulated spaceflight experiments in ground-based facilities (GBFs), such as clinostats, are each suitable only for particular investigations -- a rotating-wall vessel may be 'simulated microgravity' for cell differentiation (hours), but not DNA repair (seconds) -- and introduce confounding stimuli, such as motor vibration and fluid shear effects. This uncertainty over which biological mechanisms respond to a given form of simulated space radiation or gravity, as well as its side effects, limits our ability to baseline spaceflight data and validate mission science. Machine learning techniques autonomously identify relevant and interdependent factors in a data set given the set of desired metrics to be evaluated: to automatically identify related studies, compare data from related studies, or determine linkages between types of data in the same study. System-of-systems (SoS) machine learning models have the ability to deal with both sparse and heterogeneous data, such as that provided by the small and diverse number of space biosciences flight missions; however, they require appropriate user-defined metrics for any given data set. Although machine learning in bioinformatics is rapidly expanding, the need to combine spaceflight/GBF mission parameters with omics data is unique. This work characterizes the basic requirements for implementing the SoS approach through the System Map (SM) technique, a composite of a dynamic Bayesian network and Gaussian mixture model, in real-world repositories such as the GeneLab Data System and Life Sciences Data Archive. The three primary steps are metadata management for experimental description using open-source ontologies, defining similarity and consistency metrics, and generating testing and validation data sets. Such approaches to spaceflight and GBF omics data may soon enable unique insight into which measured phenomena correlate to biological mechanisms that are truly affected by spaceflight conditions; which are most likely to be confounded by other variables; and which are insufficiently characterized, significantly increasing existing and future science return from ISS and spaceflight missions.

Gentry, Diana↗

DOE OSTI2023

Viability of Cathodic Protection for Preventing Corrosion of Stainless Steel 316H in Molten LiF-NaF-KF

Molten fluoride salts are candidate heat transfer fluids in a number of applications such as generation IV molten salt nuclear reactors and concentrated solar power plants. However, a chief concern in the design of these systems is the corrosion of structural materials that come in contact with these molten salts. Redox control methods such as the purification of salt, the addition of active elements, and applied electrochemical potential can be efficient methods for preventing the corrosion of structural materials in molten fluoride salts. Applied electrochemical potential as a redox control method for application in molten fluoride salts has rarely been explored. This study seeks to understand the viability of impressed current cathodic protection (CP) at various currents as a redox control method to prevent corrosion of stainless steel 316H in molten LiF-NaF-KF (FLiNaK) salt. Results show that application of CP can be an effective method to prevent corrosion of SS316H in molten FLiNaK salt, but the applied current will have to be optimized to prevent undesirable side effects such as reduction of salt constituents, salt deposition on electrodes, etc.

Materials Science↗

NASA NTRS1982

A new brominated polymeric additive for flame retardant glass-filled polybutylene terephthalate

Attention is called to the undesirable effects (poor ultraviolet light stability and blooming) sometimes introduced by brominated flame retarders. A brominated polymeric additive (BPA) with little or none of these undesirable side effects is compared with decabromobiphenyl oxide (DBBPO). The additive bears the product name F-2300. It is found to be more easily dispersed than DBBPO. The F-2300 is as effective as the DBBPO in the oxygen index test. The improved efficiency of the F-2300 may be explained by its better dispersion in polybutylene terephthalate (PBT). Glass-filled PBT containing F-2300 is found to be more resistant to UV degradation than DBBPO-containing formulas. Formulations with F-2300 therefore have a longer useful outdoor life. F-2300 is a diglycidyl-type polymer containing 50 percent aromatically bound bromine. Its melting point is 112 C, and it is stable up to 372 C. It is pointed out that since its melts at a relatively low temperature, it can be introduced into the formulation as a large agglomerate and still be dispersed evenly throughout the polymer.

Nir, Z.↗

NASA NTRS1996

Dextroamphetamine: a pharmacologic countermeasure for space motion sickness and orthostatic dysfunction

Dextroamphetamine has potential as a pharmacologic agent for the alleviation of two common health effects associated with microgravity. As an adjuvant to Space Motion Sickness (SMS) medication, dextroamphetamine can enhance treatment efficacy by reducing undesirable Central Nervous System (CNS) side effects of SMS medications. Secondly, dextroamphetamine may be useful for the prevention of symptoms of post-mission orthostatic intolerance caused by cardiovascular deconditioning during spaceflight. There is interest in developing an intranasal delivery form of dextroamphetanmine for use as a countermeasure in microgravity conditions. Development of this dosage form will require an analytical detection method with sensitivity in the low ng range (1 to 100 ng/mL). During the 1995 Summer Faculty Fellowship Program, two analytical methods were developed and evaluated for their suitability as quantitative procedures for dextroamphetamine in studies of product stability, bioavailability assessment, and pharmacokinetic evaluation. In developing some of the analytical methods, beta-phenylethylamine, a primary amine structurally similar to dextroamphetamine, was used. The first analytical procedure to be evaluated involved hexane extraction and subsequent fluorescamine labeling of beta-phenylethylamine. The second analytical procedure to be evaluated involved quantitation of dextroamphetamine by an Enzyme-Linked ImmunoSorbent Assay (ELISA).

Snow, L. Dale↗

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 NTRS1982

Neurochemical background and approaches in the understanding of motion sickness

The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.

Kohl, R. L.↗

NASA NTRS2013

Benefits, Consequences, and Uncertainties of Conventional (Exercise) Countermeasure Approaches

This presentation will review the pros, cons, and uncertainties of using exercise countermeasures in hypothetical long duration exploration missions. The use of artificial gravity and exercise will be briefly discussed. One benefit to continued use of exercise is related to our extensive experience with spaceflight exercise hardware and programming. Exercise has been a part of each space mission dating back to the 1960's when simple isometric and bungee exercises were performed in the Gemini capsule. Over the next 50 years, exercise hardware improved cumulating in today's ISS suite of exercise equipment: Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), Treadmill (T2) and Advanced Resistive Exercise Device (ARED). Today's exercise equipment is the most robust ever to be flown in space and allows the variety and intensity of exercise that might reasonably be expected to maintain muscle mass and function, bone density and cardiovascular fitness. A second benefit is related to the large body of research literature on exercise training. There is a considerable body of supporting research literature including >40,000 peer reviewed research articles on exercise training in humans. A third benefit of exercise is its effectiveness. With the addition of T2 and ARED to our ISS exercise suite, crew member outcomes on standard medical tests have improved. Additionally exercise has other positive side effects such as stress relief, possible improvement of immune function, improved sleep, etc. Exercise is not without its consequences. The major cons to performance of in‐flight exercise are the time and equipment required. Currently crew are scheduled 2.5 hrs/day for exercise and there is considerable cost to develop, fly and maintain exercise hardware. While no major injuries have been reported on ISS, there is always some risk of injury with any form of exercise There are several uncertainties going forward; these relate mostly to the development of small compact robust effective exercise devices for the next generation of space vehicles. It is becoming increasingly apparent that high intensity exercise is required for maintenance of fitness and functional capability and so future hardware will need to be developed, tested and implemented that allow for a wide variety of exercise, at high intensity while likely involving low mass, volume and power. There are many unanswered issues related to the minimum number and type of exercise devices required for exploration, optimizing exercise prescriptions for these devices, whether a treadmill is absolutely required, and even whether any single countermeasure can adequately protect muscle, bone, cardiovascular and sensorimotor function.

Ploutz-Snyder, Lori↗

NASA NTRS2001

Stabilized NADH as a Countermeasure for Jet Lag

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotin amide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to receive either 20 mg of sublingual stabilized ADH (n=18) or identical placebo tablets (n=17). All participants completed computer-administered tests (including CogScreen7) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 5 of 8 cognitive and psychomotor test measures (P less than or equal to 0.5) and showed a trend for better performance on the other three measures (P less than or equal to .l0). Subjects also reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects.

Kay, Gary G.↗