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At least 109 records · Page 6

De novo designed protein inhibitors of amyloid aggregation and seeding

Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such as tau and amyloid-β (Aβ) in Alzheimer’s disease (AD) and alpha-synuclein (αSyn) in Parkinson’s disease (PD). The development and spread of amyloid fibrils within the brain correlates with disease onset and progression, and inhibiting amyloid formation is a possible route toward therapeutic development. Recent advances have enabled the determination of amyloid fibril structures to atomic-level resolution, improving the possibility of structure-based inhibitor design. In this work, we use these amyloid structures to design inhibitors that bind to the ends of fibrils, “capping” them so as to prevent further growth. Using de novo protein design, we develop a library of miniprotein inhibitors of 35 to 48 residues that target the amyloid structures of tau, Aβ, and αSyn. Biophysical characterization of top in silico designed inhibitors shows they form stable folds, have no sequence similarity to naturally occurring proteins, and specifically prevent the aggregation of their targeted amyloid-prone proteins in vitro. The inhibitors also prevent the seeded aggregation and toxicity of fibrils in cells. In vivo evaluation reveals their ability to reduce aggregation and rescue motor deficits in Caenorhabditis elegans models of PD and AD.

59 BASIC BIOLOGICAL SCIENCES↗

Modeled Microgravity Induces Neutrophil Extracellular Trap (NET)osis Formation and Reduced Phagocytosis of Polymorphonuclear Neutrophils

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell death. Previous studies in our lab have identified increased mature neutrophils, ROS and MPO production, and reduced phagocytosis in granulocytes in simulated microgravity (sug) models of hindlimb unloading (HU) in adult mice and leukocytes cultured in high-aspect rotating wall vessels (HARV-RWV). Since sug impaired phagocytosis, but improved enzymatic mediator production of MPO and redox molecules, we sought to address the third known function of PMNs, NETosis. For this, PMNs were culture in the presence or absence of the anti-oxidant N-acetyl cysteine (NAC), which rescued impaired phagocytosis that was present in sug without NAC treatment. Further, NETosis was induced in sug that was no different in the presence of NAC, suggesting NAC targets independent functions of PMNs under sug. Collectively, these results suggest modeled microgravity induced NETosis, which opens a new avenue for spaceflight studies in immune dysfunction.

Paul, Amber M.↗

Quantification of microtubule stutters: dynamic instability behaviors that are strongly associated with catastrophe

Microtubules (MTs) are cytoskeletal fibers that undergo dynamic instability (DI), a remarkable process involving phases of growth and shortening separated by stochastic transitions called catastrophe and rescue. Dissecting DI mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. We present a Statistical Tool for Automated Dynamic Instability Analysis (STADIA) that identifies and quantifies not only growth and shortening, but also a category of intermediate behaviors that we term “stutters.” During stutters, the rate of MT length change tends to be smaller in magnitude than during typical growth or shortening phases. Quantifying stutters and other behaviors with STADIA demonstrates that stutters precede most catastrophes in our in vitro experiments and dimer-scale MT simulations, suggesting that stutters are mechanistically involved in catastrophes. Related to this idea, we show that the anticatastrophe factor CLASP2γ works by promoting the return of stuttering MTs to growth. STADIA enables more comprehensive and data-driven analysis of MT dynamics compared with previous methods. The treatment of stutters as distinct and quantifiable DI behaviors provides new opportunities for analyzing mechanisms of MT dynamics and their regulation by binding proteins.

59 BASIC BIOLOGICAL SCIENCES↗

Potential roles for EVA and telerobotics in a unified worksite

Although telerobotics and extravehicular activity (EVA) are often portrayed as competitive approaches to space operations, ongoing research in the Space Systems Laboratory (SSL) has demonstrated the utility of cooperative roles in an integrated EVA/telerobotic work site. Working in the neutral buoyancy simulation environment, tests were performed on interactive roles or EVA subjects and telerobots in structural assembly and satellite servicing tasks. In the most elaborate of these tests to date, EVA subjects were assisted by the SSL's Beam Assembly Teleoperator (BAT) in several servicing tasks planned for Hubble Space Telescope, using the high-fidelity crew training article in the NASA Marshall Neutral Buoyancy Simulator. These tests revealed several shortcomings in the design of BAT for satellite servicing and demonstrated the utility of a free-flying or RMS-mounted telerobot for providing EVA crew assistance. This paper documents the past tests, including the use of free-flying telerobots to effect the rescue of a simulated incapacitated EVA subject, and details planned future efforts in this area, including the testing of a new telerobotic system optimized for the satellite servicing role, the development of dedicated telerobotic devices designed specifically for assisting EVA crew, and conceptual approaches to advanced EVA/telerobotic operations such as the Astronaut Operations Vehicle.

Akin, David↗

Surface Navigation Using Optimized Waypoints and Particle Swarm Optimization

The design priority for manned space exploration missions is almost always placed on human safety. Proposed manned surface exploration tasks (lunar, asteroid sample returns, Mars) have the possibility of astronauts traveling several kilometers away from a home base. Deviations from preplanned paths are expected while exploring. In a time-critical emergency situation, there is a need to develop an optimal home base return path. The return path may or may not be similar to the outbound path, and what defines optimal may change with, and even within, each mission. A novel path planning algorithm and prototype program was developed using biologically inspired particle swarm optimization (PSO) that generates an optimal path of traversal while avoiding obstacles. Applications include emergency path planning on lunar, Martian, and/or asteroid surfaces, generating multiple scenarios for outbound missions, Earth-based search and rescue, as well as human manual traversal and/or path integration into robotic control systems. The strategy allows for a changing environment, and can be re-tasked at will and run in real-time situations. Given a random extraterrestrial planetary or small body surface position, the goal was to find the fastest (or shortest) path to an arbitrary position such as a safe zone or geographic objective, subject to possibly varying constraints. The problem requires a workable solution 100% of the time, though it does not require the absolute theoretical optimum. Obstacles should be avoided, but if they cannot be, then the algorithm needs to be smart enough to recognize this and deal with it. With some modifications, it works with non-stationary error topologies as well.

Birge, Brian↗

Next-Generation Maneuvering System with Control-Moment Gyroscopes for Extravehicular Activities Near Low-Gravity Objects

Looking ahead to the human exploration of Mars, NASA is planning for exploration of near-Earth asteroids and the Martian moons. Performing tasks near the surface of such low-gravity objects will likely require the use of an updated version of the Manned Maneuvering Unit (MMU) since the surface gravity is not high enough to allow astronauts to walk, or have sufficient resistance to counter reaction forces and torques during movements. The extravehicular activity (EVA) Jetpack device currently under development is based on the Simplified Aid for EVA Rescue (SAFER) unit and has maneuvering capabilities to assist EVA astronauts with their tasks. This maneuvering unit has gas thrusters for attitude control and translation. When EVA astronauts are performing tasks that require ne motor control such as sample collection and equipment placement, the current control system will re thrusters to compensate for the resulting changes in center-of-mass location and moments of inertia, adversely affecting task performance. The proposed design of a next-generation maneuvering and stability system incorporates control concepts optimized to support astronaut tasks and adds control-moment gyroscopes (CMGs) to the current Jetpack system. This design aims to reduce fuel consumption, as well as improve task performance for astronauts by providing a sti er work platform. The high-level control architecture for an EVA maneuvering system using both thrusters and CMGs considers an initial assessment of tasks to be performed by an astronaut and an evaluation of the corresponding human-system dynamics. For a scenario in which the astronaut orbits an asteroid, simulation results from the current EVA maneuvering system are compared to those from a simulation of the same system augmented with CMGs, demonstrating that the forces and torques on an astronaut can be significantly reduced with the new control system actuation while conserving onboard fuel.

Carpenter, Michele↗

Deletion of Re -citrate synthase allows for analysis of contributions of tricarboxylic acid cycle directionality to the growth of Heliomicrobium modesticaldum

ABSTRACT Heliomicrobium modesticaldum,a phototrophic member of the phylum Firmicutes and family Clostridiales, possesses most of the enzymes specific to the reductive tricarboxylic acid (rTCA) cycle, except for the key enzyme, ATP-citrate lyase. It is thought to utilize a split TCA cycle when growing on pyruvate as a carbon source, in which the oxidative TCA (oTCA) direction generates most of the 2-ketoglutarate, but some can be produced in the reductive direction. Although a typicalSi-citrate synthase gene is not found in the genome, it was suggested that gene HM1_2993, annotated as homocitrate synthase, actually encodesRe-citrate synthase, which would function as the initial enzyme of the oTCA cycle. We deleted this gene to test this hypothesis and, if true, see what effect severing access to the oTCA cycle would have on this organism. The endogenous CRISPR-Cas system was used to replace the open reading frame with a selectable marker. The deletion mutants could grow on pyruvate but were unable to grow phototrophically on acetate + CO 2 as carbon source. Growth on acetate could be rescued by the addition of different electron sources (formate or ascorbate), suggesting that the oTCA cycle is used to oxidize acetate to generate electrons required to drive the carboxylation of acetyl-CoA. The deletion mutants were capable of growing in acetate minimal media without additional organic supplements beyond formate, demonstrating that the rTCA cycle can be employed to support sufficient 2-ketoglutarate production in this organism, unlike citrate synthase mutants in several chemoheterotrophic organisms utilizing the oTCA cycle. IMPORTANCE Heliobacteria are a unique group of phototrophic bacteria that are obligate anaerobes and possess a rudimentary system to use light as a source of energy. They do not make oxygen or fix carbon dioxide. Here, we explore their fundamental carbon metabolism to understand the role and operation of the central TCA cycle. This work shows both the role and operation of this cycle under different growth modes and explains how these organisms can obtain electrons to drive their biosynthetic metabolism. This foundational knowledge will be crucial in the future when attempts are made to use this organism as a platform for oxygen-sensitive synthesis of compounds in an anaerobe that can use light as its energy source.

Biotechnology & Applied Microbiology↗

Apollo-Era Life Rafts Save Hundreds of Sailors

The space shuttle is unique among spacecraft in that it glides back to Earth and lands like an airplane, usually touching ground near where it launched at Kennedy Space Center, but sometimes, in poor weather, gliding into the back-up landing site at Dryden Flight Research Center and then catching a ride back to the Cape on the back of a modified Boeing 747. Before NASA began flying the shuttle, though, astronauts had a longer, more involved trip back to base after a mission. Their capsule, called the command module, would plunge through the atmosphere before releasing a series of parachutes that would slow the craft enough for it to land on the water without too significant of an impact. Called a splashdown, this type of landing put the astronauts out in the ocean, where a specially designated U.S. Navy ship would then deploy a helicopter to retrieve the space travelers. Waiting for the rescue, the astronauts would release a highly visible marker dye into the water, then leave the command module and climb aboard a life raft. These early space pioneers had traveled thousands of miles and then landed safely back on Earth. The journey s end was in sight, but they had one more obstacle. The rotor downdraft from the helicopter coming to retrieve them, reaching sometimes as much as 100 knots per hour, was enough to flip a typical flat-bottomed life raft. Not willing to be thwarted after coming so far, NASA engineers began devising a solution. They knew they needed a highly stable inflatable raft capable of riding out the rough winds, and the solution was to make use of the most abundant resource available: water. Engineers at NASA s Johnson Space Center went to work designing and patenting a hydrodynamically stabilized ballast system that would prevent a life raft from tipping in choppy seas and fierce winds.

Source record↗

Personal Rotorcraft Design and Performance with Electric Hybridization

Recent and projected improvements for more or all-electric aviation propulsion systems can enable greater personal mobility, while also reducing environmental impact (noise and emissions). However, all-electric energy storage capability is significantly less than present, hydrocarbon-fueled systems. A system study was performed exploring design and performance assuming hybrid propulsion ranging from traditional hydrocarbon-fueled cycles (gasoline Otto and diesel) to all-electric systems using electric motors generators, with batteries for energy storage and load leveling. Study vehicles were a conventional, single-main rotor (SMR) helicopter and an advanced vertical takeoff and landing (VTOL) aircraft. Vehicle capability was limited to two or three people (including pilot or crew); the design range for the VTOL aircraft was set to 150 miles (about one hour total flight). Search and rescue (SAR), loiter, and cruise-dominated missions were chosen to illustrate each vehicle and degree of hybrid propulsion strengths and weaknesses. The traditional, SMR helicopter is a hover-optimized design; electric hybridization was performed assuming a parallel hybrid approach by varying degree of hybridization. Many of the helicopter hybrid propulsion combinations have some mission capabilities that might be effective for short range or on-demand mobility missions. However, even for 30 year technology electrical components, all hybrid propulsion systems studied result in less available fuel, lower maximum range, and reduced hover and loiter duration than the baseline vehicle. Results for the VTOL aircraft were more encouraging. Series hybrid combinations reflective of near-term systems could improve range and loiter duration by 30. Advanced, higher performing series hybrid combinations could double or almost triple the VTOL aircrafts range and loiter duration. Additional details on the study assumptions and work performed are given, as well as suggestions for future study effort.

electric motors↗

Information Systems Coordinate Emergency Management

The rescue crews have been searching for the woman for nearly a week. Hurricane Katrina devastated Hancock County, the southernmost point in Mississippi, and the woman had stayed through the storm in her beach house. There is little hope of finding her alive; the search teams know she is gone because the house is gone. Late at night in the art classroom of the school that is serving as the county s emergency operations center, Craig Harvey is discussing the search with the center s commander. Harvey is the Chief Operating Officer of a unique company called NVision Solutions Inc., based at NASA s Stennis Space Center in Bay St. Louis, only a couple of miles away. He and his entire staff have set up a volunteer operation in the art room, supporting the emergency management efforts using technology and capabilities the company developed through its NASA partnerships. As he talks to the commander, Harvey feels an idea taking shape that might lead them to the woman s location. Working with surface elevation data and hydrological principles, Harvey creates a map showing how the floodwaters from the storm would have flowed along the topography of the region around the woman s former home. Using the map, search crews find the woman s body in 15 minutes. Recovering individuals who have been lost is a sad reality of emergency management in the wake of a disaster like Hurricane Katrina in 2005. But the sooner answers can be provided, the sooner a community s overall recovery can take place. When damage is extensive, resources are scattered, and people are in dire need of food, shelter, and medical assistance, the speed and efficiency of emergency operations can be the key to limiting the impact of a disaster and speeding the process of recovery. And a key to quick and effective emergency planning and response is geographic information. With a host of Earth-observing satellites orbiting the globe at all times, NASA generates an unmatched wealth of data about our ever-changing planet. This information can be captured, analyzed, and visualized by geographic information systems (GIS) to produce maps, charts, and other tools that can reveal information essential to a wide variety of applications including emergency management. Knowing precise, real-time information about the size, location, environmental conditions, and resulting damage of an event like a flood or wildfire as well as the location and numbers of emergency responders and other resources contributes directly to the effectiveness of disaster mitigation. The need for such information is also evident when responding to homeland security threats, such as a terrorist attack. Recognizing the value of its geospatial information resources for this and other purposes, in 1998 Stennis and the state of Mississippi partnered to form what became the Enterprise for Innovative Geospatial Solutions (EIGS) industry cluster, supporting the growth of remote sensing and GIS-based research and business. As part of EIGS, several companies partnered with NASA through dual use and Small Business Innovation Research (SBIR) contracts. Among those was NVision.

Source record↗

A New Control Paradigm: Multiple Aircraft Controlled by Multiple Operators

Remotely piloted aircraft systems (RPAS) are becoming more and more prevalent in the aerospace operations. This is true in a number of diverse domains; urban air mobility, medical product delivery, infrastructure inspection, high altitude pseudo-satellites, search and rescue, auto cargo and several other applications. One aspect that all of these share in common is the need for scalability to be viable and continue to grow. The Association of Uncrewed Vehicle Systems International (AUVSI) develops an annual economic report. They project that in the first three years of integration more than 70,000 jobs will be created in the US alone, with an economic impact of more than $13.6 billion. This benefit will grow through 2025 when we foresee more than 100,000 jobs created and economic impact of $82 billion. For many of these domains to reach these levels and have the scalability needed, they will require a remote pilot to control multiple aircraft (1:N) or the extension of that, multiple pilots controlling multiple aircraft (m:N). This is a new control paradigm that raises multiple issues in various areas. The issues include regulatory, technical, safety, community acceptance and Human Factors. Human factors issues include displays, pilot workload, pilot situation awareness just to name a few. This panel brings together researchers, developers and operators that have been working in the area of m:N. They will discuss the need, the issues and some potential solutions.

multi-vehicle control↗

A Preliminary Assessment of Cognition and Fatigue During Simulated Lunar Surface Extravehicular Activities

Introduction: Artemis astronauts will be required to complete more rigorous Extravehicular Activity (EVA) schedules than during ever before. While new spacesuits are designed to sustain high physical workloads during exploration EVAs (xEVA), crewmembers must also sustain cognitive performance throughout xEVA timelines. It is therefore necessary to characterize the effects of surface xEVA tasks and timelines on cognition and fatigue. Methods: This study utilized NASA Johnson Space Center’s Active Response Gravity Offload System (ARGOS) to simulate lunar gravity and assess xEVA tasks and cognitive performance. Two subjects completed two ~5-hour EVAs in a pressurized Mark III spacesuit, completing simulated lander operations, cable routing, crew rescue, geology, payload relocation, and traverses. Subjects completed two cognitive assessments (Digit-Symbol Substitution Task (DSST) and Psychomotor Vigilance Task (PVT)) before the first and after the second simulated EVA to assess effects of xEVA tasks on processing speed and vigilant attention. Additionally, sleep (e.g., quality, duration, and efficiency) was monitored (Oura Ring) for ≥7 days prior to the simulated EVAs, as well as between each EVA, to account for possible effects of sleep decrements on cognitive metrics. Results: Cognitive performance changed minimally from pre to post EVA for both DSST (response time (RT): S1 Δ129.1ms, S2 Δ40.7ms; Accuracy: S1 preEVA = 1.0, S1 postEVA = 0.98, S2 preEVA = 1.0, S2 postEVA = 1.0) and PVT (S1 PVT RT Δ17.7 ms, S2 PVT RT Δ-2.7 ms). Subjects’ sleep duration immediately prior to EVA showed minimal deviation from baseline (Δhrs; S1 preEVA1= + 0.67, S1 preEVA2 = -.03, S2 preEVA1 = - 1.1, S2 preEVA2 = -1.39) and efficiency (Δ%; S1 preEVA1 = 0.09, S1 preEVA2 = 9.54, S2 preEVA1 = 0, S2 preEVA2= 12). Notably, sleep waketime shifted earlier for one subject by ~1 hr which may have impacted performance. Conclusion: Understanding the impacts of xEVA workloads on cognitive performance will be instrumental to future exploration mission planning and success. Future work will expand the subject pool and test new spacesuit designs to better characterize cognitive performance and impacts of sleep during simulated xEVA and inform modeling and prediction capabilities for future Artemis xEVA planning.

Taylor E. Schlotman↗

Bleach Rescues Nannochloropsis from an Obligate Parasite and Alters Microbial and Metabolite Signatures of Outdoor Cultures

Chemical agents are commonly used to protect algal crops. Yet, few studies have characterized the effects of these agents on associated microbial communities to understand effects on microbial functions relevant to algal crop production and protection. Here, we used shotgun metagenomic sequencing and untargeted exometabolite profiling to link the application of bleach, a -cidal agent used to protect algae from pests, to changes in community composition, metabolic pathways, and exometabolies - at a whole community level. Bleach protected the algal crop from crashing but altered bacterial diversity. Analysis of metagenome-assembled genomes (MAGs) revealed a classic predator-prey cycle between Oligoflexus and our target alga Nannochloropsis. Olifoflexus genomes from our study were notably similar to a previously identified BALO (Bdellovibrio and like organism), FD111, known to kill Nannochloropsis cultures, providing strong evidence that an FD111-like organism was responsible for the crash. Metabolic pathway composition differed between bleached and unbleached ponds, with abundance of twelve pathways related to stress tolerance, including the superpathway of methylglyoxal degradation, lipid IVA biosynthesis, and ectoine biosynthesis, greater in bleached ponds compared to unbleached ponds. Virulence factors related to adherence, biofilm formation, motility, and pathogenicity increased dramatically in bleached ponds with time, although this increase was not coupled with an increase in pathogens - algal or otherwise - or a decline in algal health. Our study highlights the importance of coupling 16S rRNA gene sequencing with whole genome data and other -omics tools to sketch a larger picture of community structure and function in crop systems. Moreover, our results highlight that continued long-term bleaching may lead to negative effects to crop health or downstream adverse health effects to humans or animals, depending on the algal product (i.e. human supplements or animal feedstocks). Future work on alternative treatment methods that would reduce resistance is necessary in the field.

09 BIOMASS FUELS↗

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

ABSTRACT Stenotrophomonas maltophilia expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A S. maltophilia mutant lacking the gene for 20845 was impaired for killing Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa . Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant E. coli being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede E. coli , indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the S. maltophilia T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase. IMPORTANCE Stenotrophomonas maltophilia is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to S. maltophilia infection. In hospital water systems and various types of infections, S. maltophilia co-exists with other bacteria, including other pathogens such as Pseudomonas aeruginosa . We previously demonstrated that S. maltophilia has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, S. maltophilia currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).

59 BASIC BIOLOGICAL SCIENCES↗

Insights into pathological mechanisms and interventions revealed by analyzing a mathematical model for cone metabolism

This work analyzes a mathematical model for the metabolic dynamics of a cone photoreceptor, which is the first model to account for energy generation from fatty acids oxidation of shed photoreceptor outer segments (POS). Multiple parameter bifurcation analysis shows that joint variations in external glucose, the efficiency of glucose transporter 1 (GLUT1), lipid utilization for POS renewal, and oxidation of fatty acids affect the cone’s metabolic vitality and its capability to adapt under glucose-deficient conditions. The analysis further reveals that when glucose is scarce, cone viability cannot be sustained by only fueling energy production in the mitochondria, but it also requires supporting anabolic processes to create lipids necessary for cell maintenance and repair. In silico experiments are used to investigate how the duration of glucose deprivation impacts the cell without and with a potential GLUT1 or oxidation of fatty acids intervention as well as a dual intervention. The results show that for prolonged duration of glucose deprivation, the cone metabolic system does not recover with higher oxidation of fatty acids and requires greater effectiveness of GLUT1 to recover. Finally, time-varying global sensitivity analysis (GSA) is applied to assess the sensitivity of the model outputs of interest to changes and uncertainty in the parameters at specific times. The results reveal a critical temporal window where there would be more flexibility for interventions to rescue a cone cell from the detrimental consequences of glucose shortage.

59 BASIC BIOLOGICAL SCIENCES↗

Assured crew return vehicle post landing configuration design and test

The 1991-1992 senior Mechanical and Aerospace Engineering Design class continued work on the post landing configurations for the Assured Crew Return Vehicle (ACRV) and the Emergency Egress Couch (EEC). The ACRV will be permanently docked to Space Station Freedom, fulfilling NASA's commitment of Assured Crew Return Capability in the event of an accident or illness aboard Space Station Freedom. The EEC provides medical support and a transportation surface for an incapacitated crew member. The objective of the projects was to give the ACRV Project Office data to feed into their feasibility studies. Four design teams were given the task of developing models with dynamically and geometrically scaled characteristics. Groups one and two combined effort to design a one-fifth scale model of the Apollo Command Module derivative, an on-board flotation system, and a lift attachment point system. This model was designed to test the feasibility of a rigid flotation and stabilization system and to determine the dynamics associated with lifting the vehicle during retrieval. However, due to priorities, it was not built. Group three designed a one-fifth scale model of the Johnson Space Center (JSC) benchmark configuration, the Station Crew Return Alternative Module (SCRAM) with a lift attachment point system. This model helped to determine the flotation and lifting characteristics of the SCRAM configuration. Group four designed a full scale EEC with changeable geometric and dynamic characteristics. This model provided data on the geometric characteristics of the EEC and on the placement of the CG and moment of inertia. It also gave the helicopter rescue personnel direct input to the feasibility study.

Anderson, Loren A.↗

VISUAL CONTROL OF RENDEZVOUS

Space rendezvous involving human occupants will be required in many phases of space flight. In order that rendezvous capability be concurrent with other phases of manned space flight to insure that such tasks as the rotation and addition of crews for manned space station, supply of stations and launching complexes for deep-space probes, and the emergency rescue of personnel may be carried out, it is desirable to determine the ability of a human pilot to control the rendezvous maneuver. The National Aeronautics and Space Administration has conducted a study program to determine vehicle requirements and control techniques for a number of proposed methods for performing piloted space rendezvous. The final step in each phase of the rendezvous study program has been a simulation of the man-machine combination to test its feasibility. Initially, an analytical study was conducted to determine a range of conditions that would exist at the beginning of the terminal phase of rendezvous (ref. 1). Piloted systems were investigated for rendezvous control using these initial conditions. One such study of piloted rendezvous in which all the required control information was displayed to the simulator pilot on instruments is presented in reference 2. While the control of the rendezvous maneuver by use of the instrument display was shown to be feasible, the sufficiently accurate measurement of the necessary information to operate the instrument was realized to be a difficult problem. Consideration was therefore given to the possibility of maneuvering range and range rate required for the control of the rendezvous from visual sightings made during the initial control application. To provide this capability, an analytical study was made. This analytical study, presented in reference 3, derived three techniques for obtaining range and range rate visually and conducted a simplified preliminary situation to test the three analytical techniques. The study reported herein is a continuation of the simulation work begun in reference 3, and is aimed at determining the ability of a pilot to use visual information to reduce or eliminate the need for some or all of the data that would normally be displayed on instruments.

Rendezvous↗

Small Unmanned Aerial System (UAS) Flight Testing of Enabling Vehicle Technologies for the UAS Traffic Management Project

Small unmanned aerial systems (sUAS) have been studied and results indicate that there is a large array of highly-beneficial applications. These applications are too numerous to list, but include search and rescue, fire spotting, precision agriculture, etc. to name a few. Typically sUAS vehicles weigh less than 55 pounds and will be performing flight operations in the presence of manned aircraft and other sUAS. Certain sUAS applications, such as package delivery, will include operations in the close proximity of the general public. The full benefit from sUAS is contingent upon the resolution of several technological areas to enable free and widespread use of these vehicles. Technological areas in question include, but are not limited to: autonomous sense and avoid and deconfliction of sUAS from other sUAS and manned aircraft, communications and interfaces between the vehicle and human operators, and high-reliability autonomous systems. The NASA UAS Traffic Management (UTM) project is endeavoring to develop a traffic management system and concept of operations for these types of vehicles. An extensive sUAS flight test effort was performed to partially address vehicle-related technological areas and to shape an understanding of future developmental and test efforts for vehicles intended to use the UTM traffic management system. The flight testing described herein had the following objectives: 1) Install and test Dedicated Short Range Communications (DSRC) systems developed for the automotive industry for potential sense and avoid sUAS applications; 2) Evaluate the use of cellular 4G systems to provide vehicle control; 3) Obtain high-resolution video imagery in support of image-based optical detection sense and avoid systems; 4) Acquire data in fixed-wing flight to support validation and maturation of an autonomous range containment system known as Safeguard in fixed-wing flight. A total of 53 flights were performed over 12 operational days at Beaver Dam Airpark in Elberon, VA. This work was sponsored by the UTM project that is part of the Aviation Operations and Safety Program (AOSP) at NASA.

Glaab, Louis J.↗