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At least 811 records · Page 45

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DOE OSTI2020

Determining the impacts of venoarterial extracorporeal membrane oxygenation on cerebral oxygenation using a one-dimensional blood flow simulator

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical system that provides rapid and short-term support for patients with cardiac failure. In many patients, pulmonary function is also impaired, resulting in poorly-oxygenated cardiac outflow competing against well-oxygenated VA-ECMO outflow, a condition known as North-South syndrome. North-South syndrome is a primary concern because of its potential to cause cerebral hypoxia, which has a critical influence on neurological complications often seen in this patient population. In order to reduce ischemic neurological complications, it is important to understand how clinical decisions regarding VA-ECMO parameters influence blood oxygenation. In our work, we studied the impacts of flow rate and cannulation site on oxygenation using a one-dimensional (1D) model to simulate blood flow. Our model was initially tested by comparing blood flow results to those observed from experimental work in VA-ECMO patients. The 1D model was combined with a two-phase flow model to simulate oxygenation. Additionally, the influence of various other clinician-tunable parameters on oxygenation in the common carotid arteries (CCAs) were tested, including, blood viscosity, cannula position within the insertion artery, heart rate, and systemic vascular resistance (SVR), as well as geometrical changes such as arterial radius and length. Our results indicated that blood oxygenation to the brain strongly depended on the cannula insertion site and the VA-ECMO flow rate with a weaker but potentially significant dependence on arterial radius. During femoral cannulation, VA-ECMO flow rates greater than ~4.9 L/min were needed to perfuse the CCAs. However, axillary and central cannulation began to perfuse the CCAs at significantly lower flow (~1 L/min). These results may help explain the incidence of cerebral hypoxia in this patient population and the common need to change cannulation strategies during treatment to address this clinical problem. While this work describes patient-averaged results, determining these relationships between VA-ECMO parameters and cerebral hypoxia is an important step towards future work to develop patient-specific models that clinicians can use to improve outcomes.

1D blood flow↗

NASA NTRS1995

Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

Non-NASA Center↗

NASA NTRS2002

Autonomic neural control of dynamic cerebral autoregulation in humans

BACKGROUND: The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans. METHODS AND RESULTS: We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure. CONCLUSIONS: These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.

Non-NASA Center↗

DOE OSTI2013

ARM Airborne Continuous carbon dioxide measurements

The heart of the AOS CO2 Airborne Rack Mounted Analyzer System is the AOS Manifold. The AOS Manifold is a nickel coated aluminum analyzer and gas processor designed around two identical nickel-plated gas cells, one for reference gas and one for sample gas. The sample and reference cells are uniquely designed to provide optimal flushing efficiency. These cells are situated between a black-body radiation source and a photo-diode detection system. The AOS manifold also houses flow meters, pressure sensors and control valves. The exhaust from the analyzer flows into a buffer volume which allows for precise pressure control of the analyzer. The final piece of the analyzer is the demodulator board which is used to convert the DC signal generated by the analyzer into an AC response. The resulting output from the demodulator board is an averaged count of CO2 over a specified hertz cycle reported in volts and a corresponding temperature reading. The system computer is responsible for the input of commands and therefore works to control the unit functions such as flow rate, pressure, and valve control.The remainder of the system consists of compressors, reference gases, air drier, electrical cables, and the necessary connecting plumbing to provide a dry sample air stream and reference air streams to the AOS manifold.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2013

ARM Airborne Continuous carbon dioxide measurements

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2025

PID-Regulated Heating System for PIP-II Reference Line

The Proton Improvement Project-2 centers on building a new superconducting linear particle accelerator (Linac) at Fermilab. At the heart of the accelerator is the reference line, a critical system that defines the ideal path for the particle beam as it passes through magnets, RF cavities, and other beamline elements. Temperature stability is crucial for the reliable operation of RF components, such as mixers and filters. Fluctuations affect key performance parameters like conversion loss, isolation, and linearity. To mitigate any drift caused by ambient temperature changes, a heating plate assembly is utilized to maintain key components at a controlled temperature of 40°C. The system utilizes an aluminum 36”x36”x0.5” heat plate powered by a MOSFET-based control circuit, delivering approximately 460 W of thermal energy through a resistor array. Real-time temperature feedback is provided by a PT100 Resistance Temperature Detector (RTD), which interfaces with a Proportional–Integral–Derivative (PID) control algorithm to maintain closed-loop temperature regulation. The control signal actively modulates the gate voltage of an N channel MOSFET, dynamically adjusting power delivery in response to deviations from the temperature setpoint. Simulations and LTspice models validate the functionality and responsiveness of the circuit under varying conditions. The prototype has successfully demonstrated stable thermal control, paving the way for integration into the PIP-II infrastructure. The final design will feature an expanded resistor array, as well as communication with a PLC for continuous data acquisition and diagnostics. This work directly supports Fermilab’s broader mission by contributing to the stability and reliability of core accelerator systems, enhancing the precision of particle beam delivery for future physics experiments.

Mosher, Alexander [Fermilab]↗

DOE OSTI2022

Editorial: Nanotechnology for natural products

Humans around the globe have lived through an unprecedented time. The emergence and rapid spread of coronavirus disease 2019 (COVID-19) have resulted in the loss of millions of lives, and this number is still climbing every day and hour. As a consequence, there have been drastic changes over the past two years in how we live, communicate, and work, some of which may have changed forever: remote conferencing has become a new norm for businesses, schools, and academia; work-from-home and hybrid working is now more than just acceptable in many industries; most importantly, COVID-19 has raised global awareness of infectious diseases and pandemic responses to an exceptional level. Certainly, COVID-19 is not the only disease that is causing human suffering at this moment. Other highly contagious and lethal viruses, such as the human immunodeficiency virus (HIV), Ebola, and the recent addition to the list, Monkeypox, pose extraordinary challenges to modern civilizations. On the other hand, non-communicable diseases, such as heart disease, stroke, and cancer, are still claiming the majority of deaths on a global level (World Health Organization, 2020). Before the availability of synthetic drugs, civilizations worldwide relied on natural products extracted from the environment and various organisms for healthcare. Natural products and their derivatives continue to be critical components in the drug library available today. Indeed, almost a quarter of the new drugs approved by the US Food and Drug Administration (FDA) since 1981 are natural products, botanical mixtures, or their derivatives (Newman and Cragg, 2020). Recent developments in analytical characterization, genome mining, and engineering have further increased interest in drug discovery from the pool of natural products (Atanasov et al., 2021). This Research Topic celebrates a collection of studies at the intersection of natural product research and nanotechnological advances. As a successor and extension of the Research Topic in “Nanotechnology in Traditional Medicines and Natural Products” published last year (Zhang et al., 2021), the present collection focused more on recent developments in employing the synthesis and characterization of nanostructures for the delivery of functional natural products. Specifically, the use of carrier nanostructures to conjugate or encapsulate therapeutically active natural products with carrier nanostructures could enable their robust, targeted delivery tailored to either tackle a specific disease or unlock a drug administration pathway. Over the last decade, nanostructures such as liposomes (Pattni et al., 2015) and lipid nanoparticles (Hou et al., 2021) have been developed as versatile platforms for the inclusion and delivery of a wide range of therapeutical compounds; a significant advance in this aspect is the stabilization of mRNA strands for COVID-19 vaccination recently produced by Pfizer/BioNTech and Moderna (Tenchov et al., 2021). Such engineered nanomaterials are now widely used in the development of new drugs, while regulatory forces, such as the US FDA, remain cautious with the evaluation of each product on a case-by-case basis (Wang and Grainger, 2022). In this collection, Zeng et al. provided a timely review of natural products conjugated to and contained within nanomaterials for the ongoing COVID-19 pandemic. Natural products that are potentially useful in the mitigation of this disease, such as chloroquine and curcumin, supported in nanocarrier systems, have been discussed in detail. More broadly, Cheng et al. comprehensively reviewed the use of liposomes as a nanocarrier for natural products. This article provides a summary of natural product compounds and extracts used to form liposomal structures. Readers can further enjoy the practical aspects of these engineered drugs for the treatment of specific diseases as well as insights into future directions in this field.

peptides↗

NASA NTRS2014

Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily measured in the frequency domain. Therefore, we use the power spectrum (PS), which is the Fourier transform of the ACF, to describe our inter-trial correlations. The decay of the PS yields a straight line on a log-log frequency plot, which we quantify by Beta = - (slope of PS on log-log axes). Hence, Beta is a measure of the strength of inter- trial correlations in the baseline data. Larger Beta values are indicative of longer inter-trial correlations. Experimental Approach: We will begin by performing a retrospective analysis of treadmill-gait adaptation data previously collected by Dr. Bloomberg and colleagues. Specifically, we will quantify the strength of inter-trial correlations in the baseline step cadence and heart rate data and compare it to the locomotor adaptability performance results already described by these investigators. Incorporating these datasets will also allow us to explore the applicability of (and potential limitations surrounding) the use of Beta in forecasting physiological performance. We will also perform a new experiment, in which Beta will be derived from baseline data collected during over-ground (non-treadmill) walking, which will enable us to consider locomotor performance, through the parameter Beta, under the most functionallyrelevant, natural gait condition. This experiment will incorporate two baseline and five post-training over-ground locomotion tests to explore the consistency and potential adaptability of the Beta values themselves. HYPOTHESES: We hypothesize that the strength of baseline inter-trial correlations of step cadence and heart rate will relate to locomotor adaptability. Specifically, we anticipate that individuals who show weaker longer-term inter-trial correlations in baseline step cadence data will be the better adaptors, as step cadence can be modified in real-time (i.e., online corrections are an inherent property of the locomotor system; analogous to results observed in the VOR). Conversely, because heart rate is not altered mid-beat, we expect that individuals who demonstrate stronger longer-term correlations in heart rate will be the better adaptors (analogous to results observed in the saccadic system). CONCLUSIONS: At the conclusion of this project we hope to uncover a baseline predictor of locomotor adaptability. If our hypotheses hold true, our results will demonstrate that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. The ability to predict such adaptability in the sensorimotor system has significant implications for spaceflight, where astronauts must adjust their motor programs following a change in g-level to retain movement accuracy.

Beaton, K. H.↗

NASA NTRS2010

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗

DOE OSTI2023

Microscopic Origin of Polarization Charges at Ga N / ( Al , Ga ) N Interfaces

Ga⁢N/(Al,Ga)⁢N heterojunctions are at the heart of high-electron-mobility transistors that are being adopted for high-power and high-frequency applications. The strong polarization fields present at this interface significantly enhance the density of the two-dimensional electron gas (2DEG) that is confined on the Ga⁢ N side of the junction. The microscopic origin of these electrons has been debated over the years: after excluding that they would be contributed by bulk donors, a model that identifies surface states on the (Al, Ga)⁢N surface as the source of electrons has become widely adopted. Recently, it has become clear, however, that the measured density of surface states is insufficient to account for the high electron density in the 2DEG. Here we demonstrate, based on state-of-the-art first-principles calculations, that the source of electrons is intrinsic to the overall structure and that the negative charge in the 2DEG is balanced by fixed charge on the surface. We perform a rigorous study of polarization, using our recently developed methodology for quantifying polarization fields within the finite-sized systems that can be addressed with density-functional calculations. The results show that the electrons that appear in the 2DEG originate locally at the interface, and that the net charge at the interface is predominantly compensated by fixed charge on the surface, rather than surface states. We elucidate the source of this fixed charge and associate it with surface reconstructions or the presence of heterovalent impurities (such as oxygen). Our results force a reassessment of the impact of surface states on the density of the 2DEG: rather than serving as a supply of electrons, the surface states mainly act to pin the Fermi level. Our conclusions allow a fresh interpretation of experimental observations and allow devising guidelines for optimizing carrier densities in the 2DEG.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

NASA NTRS2016

Field Test: Results of Tandem Walk Performance Following Long-Duration Spaceflight

BACKGROUND: Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel, we must prepare for unassisted landings, where crewmembers may need to perform mission critical tasks within minutes of landing. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment (FT) will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. METHODS: FT is an ongoing study of 30 long-duration ISS crewmembers. Thus far, 9 have completed the full FT (5 U.S. Orbital Segment [USOS] astronauts and 4 Russian cosmonauts) and 4 more consented and launching within the next year. This is in addition to the eighteen crewmembers that participated in the pilot FT (11 USOS and 7 Russian crewmembers). The FT is conducted three times preflight and three times during the first 24 hours after landing. All crewmembers were tested in Kazakhstan in either the medical tent at the Soyuz landing site (~one hour post-landing), or at the airport (~four hours post-landing). The USOS crewmembers were also tested at the refueling stop (~12 hours post-landing) and at the NASA Johnson Space Center (~24 hours post-landing) and a final session 7 days post-landing. Crewmembers are instrumented with 9 inertial measurement unit sensors that measure acceleration and angular displacement (APDM's Emerald Sensors) and foot pressure-sensing insoles that measure force, acceleration, and center of pressure (Moticon GmbH, Munich, Germany) along with heart rate and blood pressure recording instrumentation. The FT consists of 12 tasks, but here we will focus on the most challenging task, the Tandem Walk, which was also performed as part of pilot FT. To perform the Tandem Walk, subjects begin with their feet together, their arms crossed at their chest and eyes closed. When ready, they brought one foot forward and touched the heel of their foot to their toe, repeating with the other foot, and continuing for about 10 steps. Three trials were collected with the eyes closed and a fourth trial was collected with eyes open. There are four metrics which are used to determine the performance level of the Tandem Walk. The first is percent correct steps. For a step to be counted as correct, the foot could not touch the ground while bringing it forward (no side stepping), eyes must stay closed during the eyes closed trials, the heel and toe should be touching, or almost touching (no large gaps) and there shouldn't be more than a three second pause between steps. Three judges score each step and the median of the three scores is kept. The second metric is the average step speed, or the number of steps/time to complete them. Thirdly, the root mean squared (RMS) error in the resultant trunk acceleration is used to determine the amount of upper body instability observed during the task. Finally, the RMS error of the mediolateral center of pressure as measured by the Moticon insoles is used to determine the mediolateral instability at the foot level. These four parameters are combined into a new overall Tandem Walk Parameter. RESULTS: Preliminary results show that crewmembers perform the Tandem Walk significantly worse the first 24 hours after landing as compared to their baseline performance. We find that each of the four performance metrics is significantly worse immediately after landing. We will present the results of tandem walk performance during the FT thus far. We will also combine these with the 18 crewmembers that participated in the pilot FT, concentrating on the level of performance and recovery rate. CONCLUSION: The Tandem Walk data collected as part of the FT experiment will provide invaluable information on the performance capabilities of astronauts during the first 24 hours after returning from long-duration spaceflight that can be used in planning future Mars, or other deep-space missions with unassisted landings. FT will determine the average sensorimotor recovery timeline and inform return-to-duty guidelines for unassisted landings.

Rosenberg, M. J. F.↗

NASA NTRSDate not supplied

Preparation for an Earth Independent Medical Operations Demonstration using the Tempus ALS™ Medical Device

NASA’s exploration-class missions have severe resource constraints, long return trip durations, significant communication delays and limited resupply opportunities. Validation on the International Space Station (ISS) of medical devices that fit within Earth-Independent Medical Operations (EIMO) systems is a necessary preparation step. Key features of an EIMO medical system include: 1) technologies that support the prevention, diagnosis, and treatment of spaceflight medical events; 2) components that meet mass, volume, power and crew time/training constraints; 3) consideration of the medical skill level of the astronaut caregiver; 4) collection, storage and analysis of medical data within a central data architecture; and 5) incorporation of appropriate guidance and support tools that allow crew autonomy. The Human Research Program’s (HRP) Exploration Medical Capability (ExMC) Element and the Exploration Medical Integrated Product Team (XM-IPT) are planning an ISS technology demonstration to determine the feasibility of including a multifunctional medical device into an EIMO medical system. Demonstration Preparations: The Tempus ALS (Remote Diagnostic Technologies, Ltd., Philips Corp., Farnborough, UK) is a commercial-off-the-shelf medical device, with United States Food and Drug Administration clearance and is Conformité Européene marked in Europe. Several thousand units have been sold and are successfully operating in pre-hospital and in remote settings, such as by European Space Agency (ESA) flight surgeons and some of NASA’s commercial partners during post-flight medical operations. The Tempus ALS provides vital sign measurements such as blood pressure, electrocardiograms, heart rate, end tidal CO2, respiration rate, pulse oximetry and temperature. The device has ultrasound imaging and video laryngoscopy capabilities and has automatic or manual defibrillation modes for treating cardiac arrhythmias. It includes procedural guidance capabilities to assist in the collection of the vital sign measurements and it has various data transmission and report generation features. NASA’s HRP ExMC and XM-IPT are partnering with the ESA to demonstrate the Tempus ALS on ISS, with ESA manifesting the Tempus ALS and its accessories. ESA will compare performance of periodic health status exams and medical contingency drills performed nominally and with the Tempus ALS. NASA’s EIMO demonstration will include the use of Tempus ALS to diagnose a complaint of abdominal pain under increasingly independent circumstances. The caregiver must assess the present illness, collect vital sign measurements, and perform an abdominal ultrasound, under one of three communication situations, including real-time, with a several second delay and with a delay on the order of minutes. Expected Outcomes: Information will be gained about the feasibility, benefits, and challenges of using a multifunctional, all-in-one, medical device for medical diagnosis instead of separate devices with singular functionalities. Information will also be collected about performance differences as communication delays increase and available ground support decreases. Gaining this understanding will allow for further development of exploration medical system capabilities which takes the EIMO construct into consideration.

Beth Lewandowski↗

DOE OSTI2023

Rationally Engineered Vertically Aligned β ‐Ga 2− x W x O 3 Nanocomposites for Self‐Biased Solar‐Blind Ultraviolet Photodetectors with Ultrafast Response

Abstract With the astonishing advancement of present technology and increasing energy consumption, there is an ever‐increasing demand for energy‐efficient multifunctional sensors or transducers based on low‐cost, eco‐friendly material systems. In this context, self‐assembled vertically aligned β ‐Ga 2− x W x O 3 nanocomposite (GWO‐VAN) architecture‐assisted self‐biased solar‐blind UV photodetection on a silicon platform, which is the heart of traditional electronics is presented. Utilizing precisely controlled growth parameters, the formation of W‐enriched vertical β ‐Ga 2− x W x O 3 nanocolumns embedded into the W‐deficient β ‐Ga 2− x W x O 3 matrix is reached. Detailed structural and morphological analyses evidently confirm the presence of β ‐Ga 2− x W x O 3 nanocomposite with a high structural and chemical quality. Furthermore, absorption and photoluminescence spectroscopy explains photo‐absorption dynamics and the recombination through possible donor–acceptor energy states. The proposed GWO‐VAN framework facilitates evenly dispersed nanoregions with asymmetric donor energy state distribution and thus forms build‐in potential at the vertical β ‐Ga 2− x W x O 3 interfaces. As a result, the overall heterostructure evinces photovoltaic nature under the UV irradiation. A responsivity of ≈30 A/W is observed with an ultrafast response time (≈350 µs) under transient triggering conditions. Corresponding detectivity and external quantum efficiency are 7.9 × 10 12 Jones and 1.4 × 10 4 %, respectively. It is believed that, while this is the first report exploiting GWO‐VAN architecture to manifest self‐biased solar‐blind UV photodetection, the implication of the approach is enormous in designing electronics for extreme environment functionality and has immense potential to demonstrate drastic improvement in low‐cost UV photodetector technology.

Das, Debabrata↗

NASA NTRS2001

Effects of noradrenaline on human vagal baroreflexes

BACKGROUND: Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function. AIM: To understand better the role of NA in cardiovascular homeostasis. METHODS: We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz. RESULTS: The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (+/- SD) baseline level of 17.3+/-6.6 to 34.1+/-20.8 ms/mmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0+/-12.9 to 10.1+/-7.4 during the low NA infusion rate and to 6.2+/-6.2% during the high rate (P < 0.05 and 0.01, respectively). CONCLUSIONS: Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.

Non-NASA Center↗

NASA NTRS2015

Design and Demonstration of the Mars Organic Molecule Analyzer (MOMA) on the ExoMars 2018 Rover

The Mars Organic Molecule Analyzer (MOMA) investigation is a key astrobiology experiment scheduled to launch on the joint ESA-Roscosmos ExoMars 2018 rover mission. MOMA will examine the chemical composition of geological samples acquired from depths of up to two meters below the martian surface, where fragile organic molecules may be protected from destructive cosmic radiation and/or oxidative chemical reactions. The heart of the MOMA mass spectrometer subsystem (i.e., MOMA-MS) is a miniaturized linear ion trap (LIT) that supports two distinct modes of operation to detect: i) volatile and semi-volatile, low-to-moderate mass organics (less than or equal to 500 Da) via pyrolysis coupled with gas chromatography mass spectrometry (pyr/GCMS); and, ii) more refractory, moderate-to-high mass compounds (up to 1000 Da) via laser desorption (LDMS) at ambient Mars pressures. Additionally, the LIT mass analyzer enables selective ion trapping via multi-frequency waveform ion excitation (e.g., stored waveform inverse Fourier transform, or SWIFT), and structural characterization of complex molecules using tandem mass spectrometry (MSIMS). A high-fidelity Engineering Test Unit (ETU) of MOMAMS, including the LIT subassembly, dual-gun electron ionization source, micropirani pressure gauge, solenoid-driven aperture valve, redundant detection chains, and control electronics, has been built and tested at NASA GSFC under relevant operational conditions (pressure, temperature, etc.). Spaceflight qualifications of individual hardware components and integrated subassemblies have been validated through vibration, shock, thermal, lifetime, and performance evaluations. The ETU serves as a pathfinder for the flight model buildup, integration and test, as the ETU meets the form, fit and function of the flight unit that will be delivered to MPS in late 2015. To date, the ETU of MOMA-MS has been shown to meet or exceed all functional requirements, including mass range, resolution, accuracy, instrumental drift, and Iimit-of-detection specifications, thereby enabling the primary science objectives of the MOMA investigation and ExoMars 2018 mission.

Mars Organic Molecule Analyzer↗

DOE OSTI2016

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulates delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Designing Peptide Fossils That Model the Evolution of the Bacterial Ferredoxin Fold

Electron transfer coupled to redox chemistry is at the heart of metabolism. The proteins responsible for moving electrons (protein electron carriers) must have emerged at the origin of life. The small iron–sulfur-binding bacterial ferredoxins were likely among these first proteins. Embedded within the ferredoxin sequence and structure is a symmetry that points to an ancient gene duplication event. Little is understood about the nature of ferredoxins prior to this duplication event or what environmental factors may have driven the selection for more complex forms. The deep-time molecular history of ferredoxins goes back billions of years and cannot be reconstructed by phylogenetic analyses based on amino acid sequences. Here, we use structure-guided protein design to model a fossil half-ferredoxin stage in the evolution of this fold, the semidoxins, and their symmetric full-length counterparts, the symdoxins. Semidoxin designs homodimerize, exhibiting structural, thermodynamic, and electrochemical behaviors in most cases identical to cognate symdoxins. However, the semi- and symdoxin fossil stages behave differently when incorporated into an in vivo electron transfer complementation assay. Both can support bacterial growth dependent on protein expression. Growth rates of bacteria expressing the semidoxins are much more sensitive to oxygen than those of bacteria expressing symdoxins. Motivated by the in vivo functionality of designed semidoxins, we identified putative naturally occurring semidoxins in extant anaerobic microorganisms. This is consistent with the observed in vivo oxygen sensitivity of the semidoxin designs. One natural semidoxin is shown to be folded and redox active. However, it exists as a mixture of monomers and dimers, suggesting a potential connection between semidoxins and even simpler single iron–sulfur cluster-binding peptides.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2018

Effect Modification by Age on the Benefit or Harm of Antihypertensive Treatment for Elderly Hypertensives: A Systematic Review and Meta-analysis

Abstract BACKGROUND The influence of age on balance of benefit vs. potential harm of blood pressure (BP)-lowering therapy for elderly hypertensives is unclear. We evaluated the modifying effects of age on BP lowering for various adverse outcomes in hypertensive patients older than 60 years without specified comorbidities. METHODS All relevant randomized controlled trials (RCTs) were systematically identified. Coronary heart disease, stroke, heart failure (HF), cardiovascular death, major adverse cardiovascular events (MACE), renal failure (RF), and all-cause death were assessed. Meta-regression analysis was used to explore the relationship between achieved systolic BP (SBP) and the risk of adverse events. Random-effects meta-analysis was used to pool the estimates. RESULTS Our study included 18 RCTs (n = 53,993). Meta-regression analysis showed a lower achieved SBP related with a lower risk of stroke and cardiovascular death, but an increased risk of RF. The regression slopes were comparable between populations stratifying by age 75 years. In subgroup analysis, the relative risks of a more aggressive BP lowering strategy were similar between patients aged older or less than 75 years for all outcomes except for RF (P for interaction = 0.02). Compared to treatment with final achieved SBP 140–150 mm Hg, a lower achieved SBP (<140 mm Hg) was significantly associated with decreased risk of stroke (relative risk = 0.68; 95% confidence interval = 0.55–0.85), HF (0.77; 0.60–0.99), cardiovascular death (0.68; 0.52–0.89), and MACE (0.83; 0.69–0.99). CONCLUSIONS To treat hypertension in the elderly, age had trivial effect modification on most outcomes, except for renal failure. Close monitoring of renal function may be warranted in the management of elderly hypertension.

Huang, Chi-Jung↗