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NASA NTRS2000

A calcium-dependent protein kinase can inhibit a calmodulin-stimulated Ca2+ pump (ACA2) located in the endoplasmic reticulum of Arabidopsis

The magnitude and duration of a cytosolic Ca(2+) release can potentially be altered by changing the rate of Ca(2+) efflux. In plant cells, Ca(2+) efflux from the cytoplasm is mediated by H(+)/Ca(2+)-antiporters and two types of Ca(2+)-ATPases. ACA2 was recently identified as a calmodulin-regulated Ca(2+)-pump located in the endoplasmic reticulum. Here, we show that phosphorylation of its N-terminal regulatory domain by a Ca(2+)-dependent protein kinase (CDPK isoform CPK1), inhibits both basal activity ( approximately 10%) and calmodulin stimulation ( approximately 75%), as shown by Ca(2+)-transport assays with recombinant enzyme expressed in yeast. A CDPK phosphorylation site was mapped to Ser(45) near a calmodulin binding site, using a fusion protein containing the N-terminal domain as an in vitro substrate for a recombinant CPK1. In a full-length enzyme, an Ala substitution for Ser(45) (S45/A) completely blocked the observed CDPK inhibition of both basal and calmodulin-stimulated activities. An Asp substitution (S45/D) mimicked phosphoinhibition, indicating that a negative charge at this position is sufficient to account for phosphoinhibition. Interestingly, prior binding of calmodulin blocked phosphorylation. This suggests that, once ACA2 binds calmodulin, its activation state becomes resistant to phosphoinhibition. These results support the hypothesis that ACA2 activity is regulated as the balance between the initial kinetics of calmodulin stimulation and CDPK inhibition, providing an example in plants for a potential point of crosstalk between two different Ca(2+)-signaling pathways.

NASA Discipline Plant Biology↗

NASA NTRS2001

Time-dependent oral absorption models

The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

Non-NASA Center↗

NASA NTRS2001

Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass

BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment. OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression. DESIGN: Prospective observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia. INTERVENTIONS: Volunteers were transported to sea level; three received low-dose erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme. RESULTS: In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

Non-NASA Center↗

NASA NTRS2020

Strategic Deconfliction Performance: Results and Analysis from the NASA UTM Technical Capability Level 4 Demonstration

Unmanned Aircraft System (UAS) Traffic Management (UTM) refers to the service-based, cooperative approach to the management of small UAS in the National Airspace System that is safe, scalable, and fair. UTM provides the means to manage the airspace in a complementary manner that does not burden the current air traffic control workforce or infrastructure but allows the Air Navigation Service Provider to maintain its regulatory and operational authority of the airspace. A key feature of UTM is the ability to provide operators the means to strategically deconflict operations from others in the airspace through the digital exchange of information via supporting services. Through this approach, the four-dimensional operation volumes that encompass the intent of operators in a given area are discoverable and can be used for airspace awareness as well as planning conflict free operations that account for and avoid other operations. In certain cases, it is also possible to negotiate volume intersections for shared airspace use without the need to re-plan. In the NASA UTM concept, strategic deconfliction is the first layer of three in the overall conflict management model. The three layers of the conflict management model, which follow the International Civil Aviation Organization’s scheme [ICAO 2005] are: strategic conflict management, separate provision, and collision avoidance. In UTM, the strategic layer mostly occurs prior to departure, but is applicable to en route operations with sufficient planning horizon. The initial requirements for a strategic deconfliction capability within UTM are defined in a NASA publication [Rios 2018]. Within the concept and implementation of service-provided strategic deconfliction is the notion of priority. It is understood that there are instances in which an operation requires a priority designation within the UTM system and special handling accordingly to provide situation awareness and facilitate appropriate responses from other airspace users. Examples of situations requiring priority designation include: when an operator declares an emergency due to problems with the vehicle or its immediate surroundings; operations that are in support of certain organizations (e.g., public safety and first responders); or special missions that also require priority use of airspace (e.g., emergency medical deliveries). UAS Volume Reservations (UVRs) also relate to the topic of priority in the sense that the airspace that the volume encompasses has a different status or classification in which unassociated operations must vacate if inside, or avoid if outside, through strategic deconfliction with the volume. Operations that are specially permitted to access the UVR area are typically assigned priority status given the nature of their mission and their associated credentials. The ability to perform strategic deconfliction, handle certain operations with a priority distinction, and establish UVRs that are communicated throughout the UTM system, is predicated on an architecture that has been established through an evolutionary process in response to close collaboration with stakeholders from government and industry. Another important and influential aspect of these capabilities and architecture is the live, distributed flight tests that have been conducted across the Technical Capability Levels (TCLs) that culminated with a set of complex tests performed as part of TCL4 [Rios 2020]. The TCL4 flight test involved two FAA-designated UAS test sites building teams to collaborate with NASA’s UTM Project on the execution of several detailed, small UAS scenarios in urban environments.

conflict management↗

NASA NTRS2002

A simple way to measure daily lifestyle regularity

A brief diary instrument to quantify daily lifestyle regularity (SRM-5) is developed and compared with a much longer version of the instrument (SRM-17) described and used previously. Three studies are described. In Study 1, SRM-17 scores (2 weeks) were collected from a total of 293 healthy control subjects (both genders) aged between 19 and 92 years. Five items (1) Get out of bed, (2) First contact with another person, (3) Start work, housework or volunteer activities, (4) Have dinner, and (5) Go to bed were then selected from the 17 items and SRM-5 scores calculated as if these five items were the only ones collected. Comparisons were made with SRM-17 scores from the same subject-weeks, looking at correlations between the two SRM measures, and the effects of age and gender on lifestyle regularity as measured by the two instruments. In Study 2 this process was repeated in a group of 27 subjects who were in remission from unipolar depression after treatment with psychotherapy and who completed SRM-17 for at least 20 successive weeks. SRM-5 and SRM-17 scores were then correlated within an individual using time as the random variable, allowing an indication of how successful SRM-5 was in tracking changes in lifestyle regularity (within an individual) over time. In Study 3 an SRM-5 diary instrument was administered to 101 healthy control subjects (both genders, aged 20-59 years) for two successive weeks to obtain normative measures and to test for correlations with age and morningness. Measures of lifestyle regularity from SRM-5 correlated quite well (about 0.8) with those from SRM-17 both between subjects, and within-subjects over time. As a detector of irregularity as defined by SRM-17, the SRM-5 instrument showed acceptable values of kappa (0.69), sensitivity (74%) and specificity (95%). There were, however, differences in mean level, with SRM-5 scores being about 0.9 units [about one standard deviation (SD)] above SRM-17 scores from the same subject-weeks. SRM-5 scores also deviated more from a Gaussian distribution than did SRM-17 ones. In a study with a sample size of 101, the new SRM-5 instrument yielded scores with a mean of 4.11 and an SD of 1.13. Correlations between lifestyle regularity and age, and between lifestyle regularity and morningness appeared similar whether 5-item or 17-item SRM measures were used. When a gender difference in lifestyle regularity appeared, it was detected by both SRM-5 and SRM-17 measures.

Non-NASA Center↗

NASA NTRSDate not supplied

Multiple Probe Measurements at Uranus Motivated By Spatial Variability

Motivation: Spatial variations in the temperature field and composition of Uranus' atmosphere demonstrate a need for multiple entry probes to characterize vertical profiles in multiple locations. We will review variation of composition and temperature, which are produced by dynamical processes on a range of scales from global (polar anomalies, zonal bands) to regional (vortices, storms) [1–2]. In particular, the spatial variation of convective activity is not well understood based on existing remote sensing observations [3]. Understanding how these processes operate, and how they modulate variable composition, is key to constraining bulk atmospheric abundances. Abundances in turn provide cosmochemical constraints on planetary origins. Secondary probes at Uranus: Key measurements for secondary probes are temperature-pressure profiles, along with compositional profiles. Radio occultations are limited to shallow levels less than ~2 bar [4]. In situ temperature-pressure measurements (or atmospheric structure measurements) can unambiguously extend these results to deeper levels. Measurements with vertical resolution of at least 2 km are needed to characterize anomalies like the 1.2-bar feature from the Voyager 2 occultation at 2–6° S [4], which supports a range of temperature gradients depending on assumptions of composition. Simultaneous measurements of temperature, pressure, and composition are key to understanding this class of features. Species such as methane, hydrogen sulfide, and ammonia must be measured along a probe descent profile because they vary over several orders of magnitude due to the strong temperature dependence of their saturation vapor pressures [e.g., 5]. Results of these measurements can be interpreted to understand the potential for moist convective activity in the atmosphere. Lessons from the other giant planets: On Jupiter, the Galileo Probe's entry into a meteorologically distinct five-micron hot spot led many to interpret the local composition as column-stretched, so that well-mixed abundances were reached at deeper levels than in surrounding, unperturbed regions [6–8]. Ground-based microwave measurements and Juno data now indicate that the deep depletion of ammonia is a very widespread atmospheric characteristic not limited to 5-µm hot spots [9–11]. But in the absence of multiple probes, we do not know if the other volatiles H2S and H2O behave in the same way. The open questions for the Jupiter case strongly motivate sending multiple probes to Uranus. On Saturn, retrievals of NH3 and PH3 abundances at shallow levels vary with latitude [12], but it is unknown how deep these differences extend, which is why a Saturn probe (or probes) was a mission theme for NASA's New Frontiers 4 and 5 opportunities [13]. Challenges for secondary probes: Cost is an issue due to the perception that it involves sacrifices to other mission elements. Spacecraft trajectories may be constrained by needs for orbit insertion that limit probe deliveries to different latitudes, and additional limitations may be placed on communication windows for probe descent phases (particularly if multiple probes are released from the orbiter simultaneously) [14]. Finally, composition sensors for miniature secondary probes are not at the required technological maturity [15]. Mass spectrometers are typically too large, massive, and powerhungry, while smaller nanosensors are only beginning to be developed for planetary missions. Finally, the need for probe survival heating is most easily met by radioisotope heat sources, but these require regulatory approvals that are even more difficult to satisfy compared to standard environmental reviews [16], unless the secondary probe is designed as a core element of a mission. References: [1] Molter E.M., et al. (2021) PSJ, 2, 3. [2] Rowe-Gurney N., et al. (2021) Icar, 365, 114506. [3] Hueso R., Sánchez-Lavega A. (2019) SSRv, 215, 52. [4] Lindal G.F., et al. (1987) JGR, 92, 14987– 15001. [5] Simon A.A., et al. (2022) RemS, 14, 1518. [6] Atreya, S.K., et al. (1997) in The Three Galileos: The Man, the Spacecraft, the Telescope, pp. 249–260 (C. Barbieri et al., eds.). [7] Showman A.P., Ingersoll A.P. (1998) Icar, 132, 205–220. [8] Friedson A.J. (2005) Icar, 177, 1–17. [9] de Pater I., et al. (2001) Icar, 149, 66–78. [10] Li C., et al. (2017) GeoRL, 44, 5317–5325. [11] de Pater I., et al. (2019) Icar, 322, 168–191. [12] Fletcher L.N., et al. (2009) Icar, 202, 543–564. [13] National Research Council (2011) Vision and Voyages. [14] Sayanagi K.M., et al. (2020) SSRv, 216, 72. [15] Wong M.H. et al. (2021) BAAS, 53, 486. [16] Zide A., Mendoza-Hill A., Cheney D. (2022) COSPAR Abstracts H0.6-0012-22.

Michael H Wong↗

NASA NTRS2018

Urban Air Mobility (UAM) Market Study

The Booz Allen Team explored market size and potential barriers to Urban Air Mobility (UAM) by focusing on three potential markets – Airport Shuttle, Air Taxi, and Air Ambulance. We found that the Airport Shuttle and Air Taxi markets are viable, with a significant total available market value in the U.S. of $500 billion, for a fully unconstrained scenario. In this unconstrained best-case scenario, passengers would have the ability to access and fly a UAM at any time, from any location to any destination, without being hindered by constraints such as weather, infrastructure, or traffic volume. Significant legal and regulatory, weather, certification, public perception, and infrastructure constraints exist, which reduce the market potential for these applications to only about 0.5% of the total available market, or $2.5 billion, in the near term. However, we determined that these constraints can be addressed through ongoing intra-governmental partnerships, government and industry collaboration, strong industry commitment, and existing legal and regulatory enablers. We found that the Air Ambulance market is not a viable market if served by electric vertical takeoff and landing (eVTOL) vehicles due to technology constraints but may potentially be viable if a hybrid VTOL aircraft are utilized. The barriers and challenges we characterized in this study can be stratified according to their applicability or potential mitigation through technology as well as market maturity (Figure 1). In the near term, high cost of service will be a key economic challenge. We found potential for significant reduction in service cost through increased vehicle and component efficiency, and automation in a more mature market scenario. Weather conditions also pose a challenge to the UAM market, though there is potential for mitigation of some of these impacts through technology such as sensors enabling operations in low visibility. However, even in a mature market with advanced technology, disruptions are still likely to occur due to weather events such as thunderstorms and strong winds. High density operations will likely stress the current Air Traffic Management (ATM) system in the near term, but technology and new initiatives such as the Air Traffic Management -eXploration project (ATM-X) will enable safe and efficient integration of UAM into the National Airspace System (NAS). Current battery technology creates a barrier in the near term, especially for the Air Ambulance market, as battery weight and extensive recharging times would be needed for these operations. Advancements in battery technology, as well as use of hybrid VTOLs, could significantly reduce this barrier in the longer term. As UAM emerges as a viable mode of transportation in the near term, adverse energy and environmental impacts, particularly noise, may impact community acceptance and potentially persist as the market matures into larger-scale operations. For non-technology related challenges, we found that infrastructure constraints will create a significant barrier to UAM in the near term but could be addressed in the longer term through development and expansion of vertiports. Competition from existing modes of transportation such as ride-sharing (e.g., Lyft, Uber) and ground taxi’s pose a key barrier to UAM in the short term, which will likely evolve into competition from other emerging technologies such as autonomous cars and electric trains in the longer term. Weather events will influence other components of the operation such as passenger comfort (e.g., extreme temperatures, turbulence) and infrastructure (e.g., winter weather causing cracks and degradation in vertiports). There is also potential for these impacts to be heightened in the longer term from the increased frequency of adverse weather such as thunderstorms due to changing climatic conditions. We also found that the public has strong concerns about safety as a passenger in a piloted UAM, including “lasing” of pilots, unruly passengers, and sabotage. They would prefer that all passengers pass through a security screening process before boarding a vehicle. They would also prefer to use UAM for longer regional trips, such as flying from Washington, DC to Baltimore, MD or San Diego, CA to Los Angeles, CA. A longer term automated UAM vehicle market will face challenges due to public apprehension about automation and unmanned operations, and a preference to fly with passengers they know in an autonomous (unmanned) operational scenario.

Rohit Goyal↗

NASA NTRS1998

Cardiovascular function following reduced aerobic activity

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance, despite the accentuated aortic and cardiopulmonary baroreflex function following deconditioning.

Non-NASA Center↗