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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Modeling heart rate variability by stochastic feedback

We consider the question of how the cardiac rhythm spontaneously self-regulates and propose a new mechanism as a possible answer. We model the neuroautonomic regulation of the heart rate as a stochastic feedback system and find that the model successfully accounts for key characteristics of cardiac variability, including the 1/f power spectrum, the functional form and scaling of the distribution of variations of the interbeat intervals, and the correlations in the Fourier phases which indicate nonlinear dynamics.

Non-NASA Center↗
NASA NTRS1987

A new technique to determine the correlation between the QT interval and heart-rate for control and SIDS babies

The ability of the autonomic nervous system to alter the QT interval in response to heart rate changes is essential to cardiovascular control. An accurate way to determine the relation between QT intervals and their corresponding RR intervals is described. A computer algorithm measures the RR intervals using digital filtering and cross-correlating the QRS sections of consecutive waveforms. The QT intervals is calculated by choosing a section of, the ECG that includes the T wave and cross-correlating it with all the consecutive T waves. At least 4000 pairs of QT-RR intervals are computed for each subject and a best fit correlation function determines the relations between the QT and RR intervals. This technique enables to establish a precise correlation between RR and QT in order to distinguish between control and SIDS babies.

Non-NASA Center↗
NASA NTRS1992

Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals

Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

Non-NASA Center↗
NASA NTRS2001

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

Clinical Trial↗
NASA NTRS2000

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Non-NASA Center↗
NASA NTRS2000

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

Non-NASA Center↗
NASA NTRS2000

Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

Atrial development in the human heart: an immunohistochemical study with emphasis on the role of mesenchymal tissues

The development of the atrial chambers in the human heart was investigated immunohistochemically using a set of previously described antibodies. This set included the monoclonal antibody 249-9G9, which enabled us to discriminate the endocardial cushion-derived mesenchymal tissues from those derived from extracardiac splanchnic mesoderm, and a monoclonal antibody recognizing the B isoform of creatine kinase, which allowed us to distinguish the right atrial myocardium from the left. The expression patterns obtained with these antibodies, combined with additional histological information derived from the serial sections, permitted us to describe in detail the morphogenetic events involved in the development of the primary atrial septum (septum primum) and the pulmonary vein in human embryos from Carnegie stage 14 onward. The level of expression of creatine kinase B (CK-B) was found to be consistently higher in the left atrial myocardium than in the right, with a sharp boundary between high and low expression located between the primary septum and the left venous valve indicating that the primary septum is part of the left atrial gene-expression domain. This expression pattern of CK-B is reminiscent of that of the homeobox gene Pitx2, which has recently been shown to be important for atrial septation in the mouse. This study also demonstrates a poorly appreciated role of the dorsal mesocardium in cardiac development. From the earliest stage investigated onward, the mesenchyme of the dorsal mesocardium protrudes into the dorsal wall of the primary atrial segment. This dorsal mesenchymal protrusion is continuous with a mesenchymal cap on the leading edge of the primary atrial septum. Neither the mesenchymal tissues of the dorsal protrusion nor the mesenchymal cap on the edge of the primary septum expressed the endocardial tissue antigen recognized by 249-9G9 at any of the stages investigated. The developing pulmonary vein uses the dorsal mesocardium as a conduit to reach the primary atrial segment. Initially, the pulmonary pit, which will becomes the portal of entry for the pulmonary vein, is located along the midline, flanked by two myocardial ridges. As development progresses, tissue remodeling results in the incorporation of the portal of entry of the pulmonary vein in left atrial myocardium, which is recognized because of its high level of creatine. Closure of the primary atrial foramen by the primary atrial septum occurs as a consequence of the fusion of these mesenchymal structures. Copyright 2000 Wiley-Liss, Inc.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

[Individual peculiarities of adaptation to long-term space flights: 24-hour heart rhythm monitoring]

Presented are results of studying 24-hr variability of the cardiac rhythm which characterizes individual difference in reactions of two crew members to the same set of stresses during a 115-day MIR mission. Spacelab (USA) cardiorecorders were used. Data of monitoring revealed significantly different baseline health statuses of the cosmonauts. These functional differences were also observed in the mission. In one of the cosmonauts, the cardiac regulation changed over to a more economic functioning with the autonomous balance shifted towards enhanced sympathetic activity. After 2-3 months on mission he had almost recovered pre-launch level of regulation. In the other, the regulatory system was appreciably strained at the beginning of the mission as compared with preflight baseline. Later on, on flight months 2-3, this strain kept growing till a drastic depletion of the functional reserve. On return to Earth, this was manifested by a strong stress reaction with a sharp decline in power of high-frequency and grow in power of very low frequency components of the heart rhythm. The data suggest that adaptation to space flight and reactions in the readaptation period are dependent on initial health status of crew members, and functional reserve.

long duration↗
NASA NTRS1999

Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry

The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

Non-NASA Center↗
NASA NTRS1999

Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

Non-NASA Center↗
NASA NTRS1999

Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

Non-NASA Center↗
NASA NTRS1997

Evaluation of heart rate changes: electrocardiographic versus photoplethysmographic methods

The heart rate (HR) variation to forced deep breathing (HRDB) and to the Valsalva maneuver (Valsalva ratio; VR) are the two most widely used tests of cardiovagal function in human subjects. The HR is derived from a continuously running electrocardiographic (ECG) recording. Recently, HR derived from the arterial waveform became available on the Finapres device (FinapHR), but its ability to detect rapid changes in HR remains uncertain. We therefore evaluated HRDB and VR derived from FinapHR using ECG-derived HR (ECGHR) recordings as the standard. We also compared the averaged HR on Finapres (Finapav) with beat-to-beat Finapres (FinapBB) values. Studies were undertaken in 12 subjects with large HR variations: age, 34.5 +/- 9.3 (SD) years; six males and six females. FinapBB values were superimposable upon ECGHR for both HRDB and VR. In contrast, Finapav failed to follow ECGHR for HRDB and followed HRECG with a lag for the VR. To evaluate statistically how closely FinapHR approximated ECGHR, we undertook regression analysis, using mean values for each subject. To compare the two methods, we evaluated the significance of the difference between test and standard values. For HRDB, FinapBB reproducibly recorded HR (R2 = 0.998), and was significantly (p = 0.001) better than Finapav (R2 = 0.616; p < 0.001). For VR, HRBB generated a VR that was not significantly different from the correct values, while HRav generated a value that was slightly but consistently lower than the correct values (p < 0.001). We conclude that FinapHR reliably records HR variations in the beat-to-beat mode for cardiovascular HR tests.

Non-NASA Center↗
NASA NTRS1994

Comparing the effects of two in-flight aerobic exercise protocols on standing heart rates and VO(2peak) before and after space flight

The effects of regular aerobic exercise on orthostatic tolerance have been the subject of a long-standing controversy that will influence the use of exercise during space flight. To examine these effects, astronauts performed continuous (CE) aerobic exercise (n = 8), interval (IE) aerobic exercise (n = 4), or no (NE) exercise (n = 5) during flights of 7 to 11 days. Heart rate (HR) responses to an orthostatic challenge (stand test) were measured 10 days before flight and on landing day. VO(2peak) (graded treadmill exercise) was measured 7 to 21 days before and 2 days after flight. No significant differences across the groups were observed in standing HRs before or after flight. However, the within-group mean HRs significantly increased in the NE (71-89 beats/min) and CE (60-85 beats/min) groups after space flight. The HRs for the IE group did not significantly increase (75-86 beats/min) after space flight. VO(2peak) decreased (P < .05) in the NE (-9.5%) group, but did not change in the CE (-2.4%) and IE (1%) groups. The relationship (r = 0.237) between the delta HR and delta VO(2peak) was not significant. These preliminary results indicate that: (1) continuous exercise does not affect the orthostatic HR response after space flight; (2) interval exercise may minimize an increase in the postflight orthostatic HR; and (3) both exercise protocols can maintain VO(2peak).

NASA Discipline Musculoskeletal↗
NASA NTRS1992

Stress failure of pulmonary capillaries: role in lung and heart disease

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Review↗
NASA NTRS1992

The effects of interferon-alpha/beta in a model of rat heart transplantation

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

NASA Discipline Regulatory Physiology↗
NASA NTRS1992

Spectral analysis of heart rate dynamics in elderly persons with postprandial hypotension

Prior studies suggest that postprandial hypotension in elderly persons may be due to defective sympathetic nervous system activation. We examined autonomic control of heart rate (HR) after a meal using spectral analysis of HR data in 13 old (89 +/- 6 years) and 7 young (24 +/- 4 years) subjects. Total spectral power, an index of overall HR variability, was calculated for the frequency band between 0.01 and 0.40 Hz. Relatively low-frequency power, associated with sympathetic nervous system and baroreflex activation, was calculated for the 0.01 to 0.15 Hz band. High-frequency power, representing parasympathetic influences on HR, was calculated for the 0.15 to 0.40 Hz band. Mean arterial blood pressure declined 27 +/- 8 mm Hg by 60 minutes after the meal in elderly subjects, compared with 9 +/- 8 mm Hg in young subjects (p less than or equal to 0.0001, young vs old). The mean change in low-frequency HR power from 30 to 50 minutes after the meal was +19.4 +/- 25.3 U in young subjects versus -0.1 +/- 1.5 U in old subjects (p less than or equal to 0.02). Mean change in total power was also greater in young (19.0 +/- 26.6 U) subjects compared with old subjects (0.0 +/- 1.6 U, p greater than or equal to 0.02). Mean ratio of low:high-frequency power increased 3.1 +/- 3.3 U in young subjects vs 0.5 +/- 2.7 U in old subjects (p less than or equal to 0.01). The increase in low-frequency HR power and in the low:high frequency band ratio in young subjects is consistent with sympathetic activation in the postprandial period.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Cardiopulmonary↗
NASA NTRSDate not supplied

xEMU Wired Heart Rate Monitor

For the past several years, the Exploration Extra-Vehicular Mobility Unit (xEMU) team at NASA’s Johnson Space Center (JSC) has focused on development and testing of the xEMU to support missions to the International Space Station (ISS) and a moon landing in 2024. In that context, this paper examines the development and detailed design of the xEMU Wired Heart Rate Monitor (WHRM). This paper outlines the challenging technical requirements, significant architectural trades, technical solutions required to overcome these challenges, and a status of the detailed design. The preliminary results of Design Verification Testing (DVT) as it relates to WHRM are also provided, along with a forward strategy for final maturation into a flight-ready design.

NASA↗