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NASA NTRSDate not supplied

MicroRNA Based Countermeasure Rescue Health Risks Associated with Space Radiation and Microgravity

From our earlier work, we demonstrated a circulating microRNA (miRNA) signature that is present and involved with the general increased health risks during spaceflight. From this work we demonstrated that this miRNA signature impacted the overall biology and health with both the microgravity and space radiation components of the space environment. We showed that this miRNA signature can be an optimal biomarker for health risk and also has potential to be utilized as a countermeasure to mitigate the damage caused by the space environment by utilizing a human 3D microvascular tissue model. By applying a novel self-delivery system to target 3 miRNAs (i.e. antagomirs) from our spaceflight miRNA signature impacting cardiovascular health risks, we were able to completely mitigate damage caused by exposure to simulated Galactic Cosmic Ray (GCR) irradiation. Here we further expand on the countermeasure experiments to uncover the specific novel biology involved with this countermeasure and in vivo experiments that demonstrates that these antagomirs rescue damage caused to certain organs due to both microgravity and space radiation. Specifically, the miRNAs rescued damage to the heart and immune suppression that occurred in addition to other key biology. In addition, we have also observed with the 3D microvascular tissue model improved DNA double strand break repair machinery which can also contribute to improved recovery and protection against damage caused by space radiation. This work expands on our previous work and further uncovers how a potential minimally invasive countermeasure can be used to mitigate space environment effects.

Afshin Beheshti↗
NASA NTRS1990

EVA crewperson overboard - Simplified rescue aid (SIRA)

This paper discusses potential roles for extravehicular activity (EVA) in space logistics and the possibilities for a crewperson to become inadvertently detached from the work site. Factors which could cause the detachment will be presented and a rescue technique described. Finally, implications to the design and implementation of space logistics will be portrayed relative to minimizing or eliminating the adrift EVA crewperson possibility.

Fisher, H. T.↗
NASA NTRS1992

Heat stress and a countermeasure in the Shuttle rescueman's suit

Rescue of the astronaut flight crew from a contingency landing may risk exposure of the rescue crew to toxic propellants spilling from potentially ruptured tanks in the crew module area. An Aquala dry diver's suit has been in service by the rescue team to preclude exposure, especially in the water rescue scenario. Heat stress has become a factor of concern in recent years when older and less physically-fit team members work in this suit. Methods: Field testing was initiated using fully instrumented rescue men in a simulated scenario to determine the extent of heat stress. Two tests were accomplished, one in the normal (N) configuration and one with a proposed cooling countermeasure, the Steele vest (S). Results: Heat stress was high as indicated by average rectal temperatures (Tre) of 38.28 degrees C(100.9 degrees F) after the 45 minute protocol. Slopes of the regression equations describing the increase in Tre with time were greater (P less than 0.05) with N (0.073 plus or minus .008) compared to S (0.060 plus or minus .007). Projection of time to the 38.89 degree C (102 degree F) limit was increased by 15.3 percent with the vest. Mean skin temperature (Tsk) was higher (P less than 0.05) in N (38.33 plus or minus .11 degrees C) compared to S (34.33 plus or minus .39 degrees C). Average heart rate was higher (P less than 0.05 in N than S. Sweat loss, as measured by weight loss, was more (P less than 0.05) for N (1.09 plus or minus .09 kg versus 0.77 plus or minus .06 kg). Air usage, while slightly less for S, was not statistically different. Conclusion: The use of the cool vest provided significant relief from thermal stress in spite of the addition of 3.4 kg (7.5 pounds) weight and some loss in mobility.

Doerr, D. F.↗
NASA NTRS2010

Low-Cost Rescue Robot for Disaster Management in a Developing Country: Development of a Prototype Using Locally Available Technology

The use of robots in different fields is common and effective in developed countries. In case of incident management or emergency rescue after a disaster, robots are often used to lessen the human effort where it is either impossible or life-threatening for rescuers. Though developed countries can afford robotic-effort for pro-disaster management, the scenario is totally opposite for developing and under-developed countries to engage such a machine-help due to high cost of the machines and high maintenance cost as well. In this research paper, the authors proposed a low-cost "Rescue-Robot" for pro-disaster management which can overcome the budget-constraints as well as fully capable of rescue purposes for incident management. Here, all the research works were performed in Bangladesh - a developing country in South Asia. A disaster struck structure was chosen and a thorough survey was performed to understand the real-life environment for the prototype. The prototype was developed considering the results of this survey and it was manufactured using all locally available components and facilities.

Mahmud, Faisal↗
NASA NTRS1980

Search and rescue emergency locating transmitter detection/location procedure via TIROS satellite

A procedure is described which works effectively to detect and locate emergency locating transmitters (ELTs) and emergency position indicating radio beacons (EPIRBs) in a multisignal environment. Using data generated from several manufactured ELTs with diverse superimposed Doppler curves, as many as 9 simultaneous ELTs can be detected and located at a variety of signal strengths. It is noted that average position errors of 10 km are attainable today at signal power to noise spectral density ratios as low as 17 dB-Hz.

Wren, P. E.↗
NASA NTRS1990

Assured Crew Return Vehicle flowfield and aerodynamic characteristics

A lifting body has been proposed as a candidate for the Assured Crew Return Vehicle which will serve as crew rescue vehicle for the Space Station. The focus of this work is on body surface definition, surface and volume grid definition, and the computation of inviscid flowfields about the vehicle at wind-tunnel conditions. Very good agreement is shown between the computed aerodynamic characteristics of the vehicle at a freestream Mach number of 10 and those measured in wind-tunnel tests.

Weilmuenster, K. James↗
NASA NTRS1992

Motion-based carriage simulation of extra-vehicular activity (EVA) rescue

A research program was outlined for a series of Extra-Vehicular Activity (EVA) rescue studies. The general purpose is to get a better appreciation of the characteristics describing an EVA rescue scenario. Several studies have been completed in the Virtual Interactive Environment Workstation (VIEW) at NASA Ames Research Center. Similar studies are planned for a variety of simulators both to get more reliable results for the EVA rescue problem and to baseline the simulators against one another. Work is planned for a motion-based carriage to expand the validity of the previously obtained results.

Brody, Adam R.↗
NASA NTRS2024

Evaluation of Intranasal Scopolamine for the Prevention of Wave Motion Induced Motion Sickness While Maintaining Performance on Operationally Relevant Tasks

Motion sickness represents one of the greatest clinical challenges impacting crew activities during and following g-transitions. Our overall goal is to characterize the effectiveness of motion sickness countermeasures during controlled laboratory experiments using capsule wave motion simulation and during field testing in operational environments. This laboratory study focused on prevention of motion sickness using intranasal scopolamine using a double-blinded repeated measures design in 30 subjects (19M, 11F). Intranasal scopolamine was provided by Defender Pharmaceuticals, Inc. (DPI-386 Nasal Gel, referred to as Inscop) self-administered by a nasal pump (Aptar Pharma) that delivers 0.4 mg dose (0.2 mg / nostril). During each session, subjects were exposed to complex wave motion on a six degree-of-freedom platform that included pitch, roll and heave at provocative stimulus frequencies (0.1-0.25 Hz) while seated in an illuminated cabin deprived of external visual cues. Motion sickness symptoms were compared across treatment and placebo control sessions counterbalanced across subjects and separated by at least one week. The time-to-motion sickness endpoint was based on severe malaise, defined as symptom score of ≥8 points using the Pensacola Diagnostic Index [1]. The bioavailability of scopolamine for each session was estimated from plasma concentrations obtained every 15 min[2]. Side effects during the treatment session were minimal, and performance was not impaired on a test battery including motion perception tracking, tablet-based eye-hand coordination and psychomotor vigilance testing. The plasma concentration remained near-peak levels throughout the 45 min motion sickness testing for most subjects. The percentile ranking on the Motion Sickness Susceptibility Questionnaire [MSSQ, 3]was moderately correlated with the motion sickness time-to-endpoint during the placebo control session (rho = –0.3, p=0.056). Seventeen subjects did not reach an endpoint during their placebo session and were eliminated from subsequent analysis. Another subject was excluded due to insufficient plasma concentration during the treatment session. For the remaining 12 subjects, the change in time-to-motion sickness endpoint between placebo and treatment sessions was moderately correlated with plasma concentration (rho =0.48, p = 0.056), improving on average 4.4 ± 18.4 min, mean ± std with Inscop versus placebo. Our results are consistent with previous findings that intranasal delivery of scopolamine can be effective at reducing motion sickness symptoms with minimal cognitive or sedative side effects. Future work is needed to optimize the delivery of Inscop for rescue (treatment) of symptoms following g-transitions as one of the key advantages of this formulation is self-administration in a suited environment. We will also explore how the combination of Inscop with non-pharmaceutical sensory aids, e.g., vibrotactile feedback of Earth vertical, may further mitigate motion sickness and improve task performance.

S J Wood↗
DOE OSTI2020

Self-assembling Shell Proteins PduA and PduJ have Essential and Redundant Roles in Bacterial Microcompartment Assembly

Protein self-assembly is a common and essential biological phenomenon, and bacterial microcompartments present a promising model system to study this process. Bacterial microcompartments are large, protein-based organelles which natively carry out processes important for carbon fixation in cyanobacteria and the survival of enteric bacteria. These structures are increasingly popular with biological engineers due to their potential utility as nanobioreactors or drug delivery vehicles. However, the limited understanding of the assembly mechanism of these bacterial microcompartments hinders efforts to repurpose them for non-native functions. Here, we comprehensively investigate proteins involved in the assembly of the 1,2-propanediol utilization bacterial microcompartment from Salmonella enterica serovar Typhimurium LT2, one of the most widely studied microcompartment systems. We first demonstrate that two shell proteins, PduA and PduJ, have a high propensity for self-assembly upon overexpression, and we provide a novel method for self-assembly quantification. Using genomic knock-outs and knock-ins, we systematically show that these two proteins play an essential and redundant role in bacterial microcompartment assembly that cannot be compensated by other shell proteins. At least one of the two proteins PduA and PduJ must be present for the bacterial microcompartment shell to assemble. We also demonstrate that assembly-deficient variants of these proteins are unable to rescue microcompartment formation, highlighting the importance of this assembly property. Our work provides insight into the assembly mechanism of these bacterial organelles and will aid downstream engineering efforts.

1,2-propanediol utilization MCP↗
NASA NTRS1994

Attitude stability of a spinning spacecraft during appendage deployment/retraction

The work presented is motivated by the need for a national satellite rescue policy, not the ad hoc policy now in place. In studying different approaches for a national policy, the issue of capture and stabilization of a tumbling spacecraft must be addressed. For a rescue mission involving a tumbling spacecraft, it may be advantageous to have a rescue vehicle which is compact and 'rigid' during the rendezvous/capture phase. After capture, passive stabilization techniques could be utilized as an efficient means of detumbling the resulting system (i.e., both the rescue vehicle and captures spacecraft). Since the rescue vehicle is initially compact and 'rigid,' significant passive stabilization through energy dissipation can only be achieved through the deployment of flexible appendages. Once stabilization is accomplished, retraction of the appendages before maneuvering the system to its final destination may also prove advantageous. It is therefore of paramount interest that we study the effect of appendage deployment/retraction on the attitude stability of a spacecraft. Particular interest should be paid to appendage retraction, since if this process is destabilizing, passive stabilization as proposed may not be useful. Over the past three decades, it has been an 'on-again-off-again affair' with the problem of spacecraft appendage deployment. In most instances, these studies have been numerical simulations of specific spacecraft configurations for which there were specific concerns. The primary focus of these studies was the behavior of the appendage during deployment; the effects of appendage retraction was considered only in one of these studies. What is missing in the literature is a thorough study of the effects of appendage deployment/retraction on the attitude stability of a spacecraft. This paper presents a rigorous analysis of the stability of a spinning spacecraft during the deployment or the retraction of an appendage. The analysis is simplified such that meaningful insights into the problem can be inferred; it is not overly simplified such that critical dynamical behavior is neglected. The system is analyzed assuming that the spacecraft hub is rigid. The appendage deployment mechanism is modeled as a point mass on a massless rod whose length undergoes prescribed changes. Simplified flexibility effects of the appendage are included. The system is examined for stability by linearizing the equations in terms of small deviations from steady, noninterfering coning motion. Routh's procedure for analyzing small deviations from steady motion in dynamical systems is utilized in the analysis. The system of equations are nondimensionalized to facilitate parametric studies. The results are presented in terms of a reduced number of nondimensional parameters so that some general conclusions may be drawn. Verification of the linear analysis is presented through numerical simulations of the complete nonlinear, nonautonomous, coupled equations.

Fitz-Coy, Norman↗
DOE OSTI2024

Five amino acid mismatches in the zinc-finger domains of Cellulose Synthase 5 and Cellulose Synthase 6 cooperatively modulate their functional properties by controlling homodimerization in Arabidopsis

Cellulose synthase 5 (CESA5) and CESA6 are known to share substantial functional overlap. In the zinc-finger domain (ZN) of CESA5, there are five amino acid (AA) mismatches when compared to CESA6. These mismatches in CESA5 were replaced with their CESA6 counterparts one by one until all were replaced, generating nine engineered CESA5s. Each N-terminal enhanced yellow fluorescent protein-tagged engineered CESA5 was introduced to prc1-1, a cesa6 null mutant, and resulting mutants were subjected to phenotypic analyses. For this work, we found that five single AA-replaced CESA5 proteins partially rescue the prc1-1 mutant phenotypes to different extents. Multi-AA replaced CESA5s further rescued the mutant phenotypes in an additive manner, culminating in full recovery by CESA5 G43R + S49T+S54P+S80A+Y88F . Investigations in cellulose content, cellulose synthase complex (CSC) motility, and cellulose microfibril organization in the same mutants support the results of the phenotypic analyses. Bimolecular fluorescence complementation assays demonstrated that the level of homodimerization in every engineered CESA5 is substantially higher than CESA5. The mean fluorescence intensity of CSCs carrying each engineered CESA5 fluctuates with the degree to which the prc1-1 mutant phenotypes are rescued by introducing a corresponding engineered CESA5. Taken together, these five AA mismatches in the ZNs of CESA5 and CESA6 cooperatively modulate the functional properties of these CESAs by controlling their homodimerization capacity, which in turn imposes proportional changes on the incorporation of these CESAs into CSCs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

An integrated host-microbiome response to atrazine exposure mediates toxicity in Drosophila

Abstract The gut microbiome produces vitamins, nutrients, and neurotransmitters, and helps to modulate the host immune system—and also plays a major role in the metabolism of many exogenous compounds, including drugs and chemical toxicants. However, the extent to which specific microbial species or communities modulate hazard upon exposure to chemicals remains largely opaque. Focusing on the effects of collateral dietary exposure to the widely used herbicide atrazine, we applied integrated omics and phenotypic screening to assess the role of the gut microbiome in modulating host resilience in Drosophila melanogaster . Transcriptional and metabolic responses to these compounds are sex-specific and depend strongly on the presence of the commensal microbiome. Sequencing the genomes of all abundant microbes in the fly gut revealed an enzymatic pathway responsible for atrazine detoxification unique to Acetobacter tropicalis . We find that Acetobacter tropicalis alone, in gnotobiotic animals, is sufficient to rescue increased atrazine toxicity to wild-type, conventionally reared levels. This work points toward the derivation of biotic strategies to improve host resilience to environmental chemical exposures, and illustrates the power of integrative omics to identify pathways responsible for adverse health outcomes.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2009

Hubble Space Telescope Crew Rescue Analysis

In the aftermath of the 2003 Columbia accident NASA removed the Hubble Space Telescope (HST) Servicing Mission 4 (SM4) from the Space Shuttle manifest. Reasons cited included concerns that the risk of flying the mission would be too high. There was at the time no viable technique to repair the orbiter s thermal protection system if it were to be damaged by debris during ascent. Furthermore in the event of damage, since the mission was not to the International Space Station, there was no safe haven for the crew to wait for an extended period of time for a rescue. The HST servicing mission was reconsidered because of improvements in the ascent debris environment, the development of techniques for the astronauts to perform on orbit repairs to damage thermal protection, and the development of a strategy to provide a crew rescue capability. However, leading up to the launch of servicing mission, the HST crew rescue capability was a recurring topic. For HST there was a limited amount of time available to perform a crew rescue because of the limited consumables available on the Orbiter. The success of crew rescue depends upon several factors including when a problem is identified, when and to what extent power down procedures are begun, and where the rescue vehicle is in its ground processing cycle. Severe power downs maximize crew rescue success but would eliminate the option for the orbiter servicing the HST to attempt a landing. Therefore, crew rescue success needed to be weighed against preserving the ability of the orbiter to have landing option in case there was a problem with the rescue vehicle. This paper focuses on quantification of the HST mission loss of crew rescue capability using Shuttle historical data and various power down capabilities. That work supported NASA s decision to proceed with the HST service mission, which was successfully completed on May 24th 2009.

Hamlin, Teri L.↗
NASA NTRS1987

Power sources for search and rescue 406 MHz beacons

The results of a study directed at the selection of a commercially available, safe, low cost, light weight and long storage life battery for search and rescue (Sarsat) 406 MHz emergency beacons are presented. In the course of this work, five electrochemical systems (lithium-manganese dioxide, lithium-carbon monofluoride, lithium-silver vanadium oxide, alkaline cells, and cadmium-mercuric oxide) were selected for limited experimental studies to determine their suitability for this application. Two safe, commercially available batteries (lithium-manganese dioxide and lithium-carbon monofluoride) which meet the near term requirements and several alternatives for the long term were identified.

Attia, Alan I.↗
NASA NTRS1989

NASA spinoffs to public service

The National Aeronautics and Space Administration (NASA) Technology Utilization (TU) Division of the Office of Commercial Programs has been quite successful in directing the transfer to technology into the public sector. NASA developments of particular interest have been those in the areas of aerodynamics and aviation transport, safety, sensors, electronics and computing, and satellites and remote sensing. NASA technology has helped law enforcement, firefighting, public transportation, education, search and rescue, and practically every other sector of activity serving the U.S. public. NASA works closely with public service agencies and associations, especially those serving local needs of citizens, to expedite technology transfer benefits. A number of examples exist to demonstrate the technology transfer method and opportunities of NASA spinoffs to public service.

Ault, L. A.↗
NASA NTRS2020

March of the Interns

Summer 2019 brought 70 interns — from Puerto Rico, 44 continental US states, Sweden, and the Republic of Trinidad and Tobago — into the NASA Ames Aeromechanics Branch. Some were high school students learning engineering for the first time, while most were mechanical and aerospace engineering students, though two physics majors and a math major jumped into the mix to provide balance. This year’s interns completed work on 30 different projects with a collective of 30,000 dedicated hours of work. The projects this year were on urban air mobility (UAM), search and rescue vehicle design, all things Mars, Titan exploration concept designs, 3D modeling (i.e. computer aided design, CAD), computational fluid dynamics (CFD), and much more. Last year we addressed the question of what to do with an army of interns. This year, we are following its path to change the world.

Dromiack, Hannah↗
DOE OSTI2022

Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content

Transcription Factor 4 ( TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4 . We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2010

Lunar Dust-Tolerant Electrical Connector

An electrical connector was developed that is tolerant of the presence of lunar dust. Novel features of the connector include the use of a permeable membrane to act both as a dust barrier and as a wiper to limit the amount of dust that makes its way into the internal chamber of the connector. The development focused on the Constellation lunar extravehicular activity (EVA) spacesuit s portable life support system (PLSS) battery recharge connector; however, continued research is applying this technology to other lunar surface systems such as lunar rover subsystems and cryogenic fluid transfer connections for in-situ resource utilization (ISRU) applications. Lunar dust has been identified as a significant and present challenge in future exploration missions. In addition to posing contamination and health risks for human explorers, the interlocking, angular nature of lunar dust and its broad grain size distribution make it particularly harmful to mechanisms with which it may come into contact. All Apollo lunar missions experienced some degree of equipment failure because of dust, and it appears that dust accumulation on exposed material is unavoidable and difficult to reverse. Both human EVA and ISRU activities are on the mission horizon and are paramount to the establishment of a permanent human base on the Moon. Reusable and dust-tolerant connection mechanisms are a critical component for mission success. The need for dust-tolerant solutions is also seen in utility work and repair, mass transit applications, construction, mining, arctic and marine environments, diving (search and rescue), and various operations in deserts, where dust or sand clogging and coating different mechanisms and connections may render them difficult to operate or entirely inoperable.

Herman, Jason↗