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At least 379 records · Page 21

Exercise and pharmacological countermeasures for bone loss during long-duration space flight

Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

NASA Discipline Musculoskeletal↗

IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

Non-NASA Center↗

Planetary Protection Technologies: Technical Challenges for Mars Exploration

The search for life in the solar system, using either in situ analysis or sample return, brings with it special technical challenges in the area of planetary protection. Planetary protection (PP) requires planetary explorers to preserve biological and organic conditions for future exploration and to protect the Earth from potential extraterrestrial contamination that could occur as a result of sample return to the Earth-Moon system. In view of the exploration plans before us, the NASA Solar System Exploration Program Roadmap published in May 2003 identified planetary protection as one of 13 technologies for "high priority technology investments." Recent discoveries at Mars and Jupiter, coupled with new policies, have made this planning for planetary protection technology particularly challenging and relevant.New missions to Mars have been formulated, which present significantly greater forward contamination potential. New policies, including the introduction by COSPAR of a Category IVc for planetary protection, have been adopted by COSPAR in response. Some missions may not be feasible without the introduction of new planetary protection technologies. Other missions may be technically possible but planetary protection requirements may be so costly to implement with current technology that they are not affordable. A strategic investment strategy will be needed to focus on technology investments designed to enable future missions and reduce the costs of future missions. This presentation will describe some of the potential technological pathways that may be most protective.

planetary protections↗

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

Configuration and Projected Capabilities of the Common Habitat Medical Care Facility

The Common Habitat is a large, long-duration habitat being explored as part of a conceptual study (not an active NASA program) that uses an SLS core stage Liquid Oxygen (LOX) tank as its primary structure. It is intended for use on the Moon as part of a permanently occupied outpost, on Mars as part of an outpost that will be occupied for hundreds of days at a time, and in deep space as part of the Deep Space Exploration Vehicle where it will support crewed missions up to 1200 days in duration. A study of internal orientation and crew size resulted in a Common Habitat configuration sized for a crew of eight with a three-deck horizontal orientation. Additional work outside the scope of this paper is developing a vertical translation system, a crew mobility aids system based on wearable gecko-derived grippers, and a crew seating/restraint system. These systems are all assumed for use in conjunction with the Medical Care Facility, which is needed to maintain crew well-being during these missions, where distance from Earth precludes the possibility of evacuation to Earth. This paper describes recent improvements in the Common Habitat Medical Care Facility and associated benefits for crew survivability in long duration missions beyond Earth orbit. These improvements were made with the assistance of a NASA Pathways intern whose experience includes a tour of duty in Afghanistan as an Army combat medic with the 691st GHOST-T, attached to the 1st and 7th US Special Forces Groups as part of Operation Freedom’s Sentinel, where he helped provide far-forward surgical capabilities in austere combat environments. The initial baseline Medical Care Facility was developed working in conjunction with University of Houston Space Architecture graduate students. The facility was placed on the upper deck of the Common Habitat in a location that provided privacy, operational volume, and was close to the vertical translation pathway. The notional outfitting repurposed component CAD models from unrelated studies and notionally indicated a level of care roughly equivalent to that aboard the International Space Station. The CAD modeling provided notional stowage volumes, a deployable surface, some fixed equipment, an ultrasound, and a potentially reconfigurable treatment table. While this facility is clearly a competent arrangement, it was desired to leverage available expertise and upgrade the station given the vast distances from Earth to be experienced by the Common Habitat. Key driving requirements applied to the upgrade included to provide Medical Level of Care V, offer enhanced telemedicine capabilities, provide patient physical accommodation, provide caregiver access to the patient from all sides, include sliding pocket doors for access to hygiene and to the Vertical Translation System, and to add any additional capability possible for the best achievable medical care. The first step in the facility upgrade was to quantify the current medical inventory on the International Space Station and ensure that sufficient stowage volume was present for this purpose. To that end, the ISS medical kits were reviewed, and eight full size mid deck lockers were placed in the facility. A number of additional devices were also added, based on the intern’s combat medic experience. Also, two fixed shelves and one horizontal work surface were added to the Medical Care Facility, with the shelves providing storage space for the additional devices and the work surface providing a location for the caregiver to work or stage equipment. Four display monitors were added to the wall above the horizontal work surface, supporting data display, telemedicine, conferencing, or other needs. The existing treatment table was replaced with a mobile surgical stretcher-chair. Two additional doors were added to the Medical Care Facility. One leads directly to the hygiene compartment, allowing it to support medical operations in addition to providing galley/wardroom support. The other door leads directly into the Vertical Translation System. The wall adjacent to the subsystems bay was moved, adding additional volume to the Medical Care Facility. This improved caregiver access to the patient and allowed for a larger number of caregivers to be present. It also provided options for relocation of support equipment relative to the patient as needed. In the upgraded Medical Care Facility, the Surgical Stretcher-Chair and the Vertical Translation System can work together to provide incapacitated crew member transport from a site of injury on any deck of the Common Habitat to the Medical Care Facility. It can also support patient treatment in a variety of positions including a variety of sitting postures and a supine posture at a variety of pitch angles. The facility can also support caregiver office work for review of examination results, private consultation, inventory and maintenance, and a variety of other purposes. A forward activity will be to conduct evaluations of the Medical Care Facility with different medical scenarios. Additionally, ambient and task lighting selections remain as forward work. The eight mid deck lockers can be augmented to use as portable equipment carts, similar to a manner in which maintenance facility stowage was used as portable carts during the NASA Desert Research and Technology Studies in the Constellation Program. Trash accommodation will also need forward work to assess, including provision for wet trash, dry trash, and biological waste. It will be important to assess a redesign of the surgical stretcher-chair. The commercial version used in the upgrade can only enable vertical translation in the seated configuration, requiring the patient to bend both hips and knees. A possible redesign of the chair will allow for vertical translation without requiring any bending at the hip or knees. Also, the commercial version is wheeled, making it mobile in gravity but unanchored in microgravity. Work will be needed to adapt the chair for gravity-independent performance. The hygiene compartment can be redesigned for dual-use medical scrub and galley handwash facility. Pending sufficient volume, it may also be possible to place sanitation equipment in this location to clean medical tools. Finally, most space architectures have never allowed for more than one incapacitated crew member, but several scenarios could potentially injure two or more crew in the same incident. This facility could be assessed to determine its present ability to address two or more injured crew in parallel and determine the potential upper limit for number of treatable crew in a multi-crew injury scenario, or to treat polytrauma of a single patient.

Habitat↗

Configuration and Projected Capabilities of the Common Habitat Medical Care Facility

The Common Habitat is a large, long-duration habitat being explored as part of a conceptual study (not an active NASA program) that uses an SLS core stage Liquid Oxygen (LOX) tank as its primary structure. It is intended for use on the Moon as part of a permanently occupied outpost, on Mars as part of an outpost that will be occupied for hundreds of days at a time, and in deep space as part of the Deep Space Exploration Vehicle where it will support crewed missions up to 1200 days in duration. A study of internal orientation and crew size resulted in a Common Habitat configuration sized for a crew of eight with a three-deck horizontal orientation. Additional work outside the scope of this paper is developing a vertical translation system, a crew mobility aids system based on wearable gecko-derived grippers, and a crew seating/restraint system. These systems are all assumed for use in conjunction with the Medical Care Facility, which is needed to maintain crew well-being during these missions, where distance from Earth precludes the possibility of evacuation to Earth. This paper describes recent improvements in the Common Habitat Medical Care Facility and associated benefits for crew survivability in long duration missions beyond Earth orbit. These improvements were made with the assistance of a NASA Pathways intern whose experience includes a tour of duty in Afghanistan as an Army combat medic with the 691st GHOST-T, attached to the 1st and 7th US Special Forces Groups as part of Operation Freedom’s Sentinel, where he helped provide far-forward surgical capabilities in austere combat environments. The initial baseline Medical Care Facility was developed working in conjunction with University of Houston Space Architecture graduate students. The facility was placed on the upper deck of the Common Habitat in a location that provided privacy, operational volume, and was close to the vertical translation pathway. The notional outfitting repurposed component CAD models from unrelated studies and notionally indicated a level of care roughly equivalent to that aboard the International Space Station. The CAD modeling provided notional stowage volumes, a deployable surface, some fixed equipment, an ultrasound, and a potentially reconfigurable treatment table. While this facility is clearly a competent arrangement, it was desired to leverage available expertise and upgrade the station given the vast distances from Earth to be experienced by the Common Habitat. Key driving requirements applied to the upgrade included to provide NASA’s Medical Level of Care V, offer enhanced telemedicine capabilities, provide patient physical accommodation, provide caregiver access to the patient from all sides, include sliding pocket doors for access to hygiene and to the Vertical Translation System, and to add any additional capability possible for the best achievable medical care. The first step in the facility upgrade was to quantify the current medical inventory on the International Space Station and ensure that sufficient stowage volume was present for this purpose. To that end, the ISS medical kits were reviewed, and eight full size mid deck lockers were placed in the facility. A number of additional devices were also added, based on the co-author’s combat medic experience. Also, two fixed shelves and one horizontal work surface were added to the Medical Care Facility, with the shelves providing storage space for the additional devices and the work surface providing a location for the caregiver to work or stage equipment. Four display monitors were added to the wall above the horizontal work surface, supporting data display, telemedicine, conferencing, or other needs. The existing treatment table was replaced with a mobile surgical stretcher-chair. Two additional doors were added to the Medical Care Facility. One leads directly to the hygiene compartment, allowing it to support medical operations in addition to providing galley/wardroom support. The other door leads directly into the Vertical Translation System. The wall adjacent to the subsystems bay was moved, adding additional volume to the Medical Care Facility. This improved caregiver access to the patient and allowed for a larger number of caregivers to be present. It also provided options for relocation of support equipment relative to the patient as needed. In the upgraded Medical Care Facility, the Surgical Stretcher-Chair and the Vertical Translation System can work together to provide incapacitated crew member transport from a site of injury on any deck of the Common Habitat to the Medical Care Facility. It can also support patient treatment in a variety of positions including a variety of sitting postures and a supine posture at a variety of pitch angles. The facility can also support caregiver office work for review of examination results, private consultation, inventory and maintenance, and a variety of other purposes. A forward activity will be to conduct evaluations of the Medical Care Facility with different medical scenarios. Additionally, ambient and task lighting selections remain as forward work. The eight middeck lockers can be augmented to use as portable equipment carts, similar to a manner in which maintenance facility stowage was used as portable carts during the NASA Desert Research and Technology Studies in the Constellation Program. Trash accommodation will also need forward work to assess, including provision for wet trash, dry trash, and biological waste. It will be important to assess a redesign of the surgical stretcher-chair. The commercial version used in the upgrade can only enable vertical translation in the seated configuration, requiring the patient to bend both hips and knees. A possible redesign of the chair will allow for vertical translation without requiring any bending at the hip or knees. Also, the commercial version is wheeled, making it mobile in gravity but unanchored in microgravity. Work will be needed to adapt the chair for gravity-independent performance. The hygiene compartment can be redesigned to serve both as a medical scrub facility and for galley hand washing. Pending sufficient volume, it may also be possible to place sanitation equipment in this location to clean medical tools. Finally, most space architectures have never allowed for more than one incapacitated crew member, but several scenarios could potentially injure two or more crew in the same incident. This facility could be assessed to determine its present ability to address two or more injured crew in parallel and determine the potential upper limit for number of treatable crew in a multi-crew injury scenario, or to treat polytrauma of a single patient.

Common Habitat↗

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post-Bed Rest and Space Flight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts are affected will improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience greater challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. This data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post spaceflight and bed rest adaptive capability. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive ability, brain structure, brain function, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to mitigate the deleterious effects of spaceflight.

Mulavara, A. P.↗

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genotypic markers of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. These data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. To date we have completed a study on 15 normal subjects with all of the above measures. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

LEIA: An Investigation of Radiation Risks to Biology at the Lunar South Pole

Radiation and reduced gravity pose biological risks to crewed deep space exploration. At the cellular level, radiation damage can be amplified by reduced gravity. Empirical evidence on cellular responses to beyond low Earth orbit (BLEO) environments is imperative to develop effective countermeasures for crew health and in-space biomanufacturing. The Lunar Explorer Instrument for Space Biology Applications (LEIA) project is developing an instrument suite to be delivered to the south polar region of the Moon by the Commercial Lunar Payload Services (CLPS) program. This presentation will provide an overview of the LEIA hardware, experiments, and mission timeline. The LEIA instruments include the BioSensor, the ARES charged particle detector, and the Mini-FND. The BioSensor is an autonomous light emitting diode (LED)-based spectrophotometer and microfluidic incubator. The BioSensor activates yeast cultures and can measure cell growth, metabolic activity, and carotenoid production. The ARES is a Timepix-based charged particle radiation detector that measures dose, dose rate, and linear energy transfer spectra. The Mini-FND is a fast neutron detector that measures albedo neutron flux and energy spectra. Combined, these instruments will be used for yeast genetics experiments to quantify growth, metabolism, and synthetic biology-enabled production of human nutrients, while taking real time measurements of biologically relevant radiation exposure on the lunar surface. These data will be used to test the importance of selected DNA damage repair and reactive oxygen species defense pathways in mitigating cellular damage from lunar surface radiation.

Yeast↗

LEIA: An Investigation of Radiation Risks to Biology at the Lunar South Pole

Radiation and reduced gravity pose biological risks to crewed deep space exploration. At the cellular level, radiation damage can be amplified by reduced gravity. Empirical evidence on cellular responses to beyond low Earth orbit (BLEO) environments is imperative to develop effective countermeasures for crew health and in-space biomanufacturing. The Lunar Explorer Instrument for Space Biology Applications (LEIA) project is developing an instrument suite to be delivered to the south polar region of the Moon by the Commercial Lunar Payload Services (CLPS) program. This presentation will provide an overview of the LEIA hardware, experiments, and mission timeline. The LEIA instruments include the BioSensor, the ARES charged particle detector, and the Mini-FND. The BioSensor is an autonomous light emitting diode (LED)-based spectrophotometer and microfluidic incubator. The BioSensor activates yeast cultures and can measure cell growth, metabolic activity, and carotenoid production. The ARES is a Timepix-based charged particle radiation detector that measures dose, dose rate, and linear energy transfer spectra. The Mini-FND is a fast neutron detector that measures albedo neutron flux and energy spectra. Combined, these instruments will be used for yeast genetics experiments to quantify growth, metabolism, and synthetic biology-enabled production of human nutrients, while taking real time measurements of biologically relevant radiation exposure on the lunar surface. These data will be used to test the importance of selected DNA damage repair and reactive oxygen species defense pathways in mitigating cellular damage from lunar surface radiation.

Yeast↗

Pathways of proton transfer in the light-driven pump bacteriorhodopsin

The mechanism of proton transport in the light-driven pump bacteriorhodopsin is beginning to be understood. Light causes the all-trans to 13-cis isomerization of the retinal chromophore. This sets off a sequential and directed series of transient decreases in the pKa's of a) the retinal Schiff base, b) an extracellular proton release complex which includes asp-85, and c) a cytoplasmic proton uptake complex which includes asp-96. The timing of these pKa changes during the photoreaction cycle causes sequential proton transfers which result in the net movement of a proton across the protein, from the cytoplasmic to the extracellular surface.

NASA Discipline Number 52-30↗

A reevaluation of the vestibulo-ocular reflex: new ideas of its purpose, properties, neural substrate, and disorders

Conventional views of the vestibulo-ocular reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved--locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (< 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

Review↗

The Global Exploration Roadmap: Opportunities for Lunar Science

The Global Exploration Roadmap (GER) has been developed by the International Space Exploration Coordination Group (ISECG comprised of 14 space agencies) to define various pathways to getting humans beyond low Earth orbit and eventually to Mars. Such pathways include visiting asteroids or the Moon before going on to Mars. This document has been written at a very high level and many details are still to be determined. However, a number of important papers regarding international space exploration can form a basis for this document.This poster will focus on developing the Lunar Vicinity scenario by adding detail via mapping a number of recent reportsdocuments into the GER. The documents highlighted here are in no way meant to be all encompassing and other documents can and should be added, (e.g., the JAXA Space Exploration Roadmap). This exercise is intended to demonstrate that existing documents can be mapped into the GER despite the major differences in granularity, and that this mapping is a way to promote broader national and international buy-in to the Lunar Vicinity scenario.The documents used here are: the Committee on Space Research (COSPAR) Panel on Exploration report on developing a global space exploration program, the Strategic Knowledge Gaps (SKGs) report from the Lunar Exploration Analysis Group (LEAG), the Lunar Exploration Roadmap developed by LEAG, the National Research Council report Scientific Context for the Exploration of the Moon (SCEM), and two journal articles, the scientific rationale for resuming lunar surface exploration, and the astrobiological benefits of human space exploration.In addition, the ISECG is in the process of developing a Science White Paper (SWP) to accompany the next edition of the GER, due in late 2016. The SWP will be an important tool to communicate science which will be able to be accomplished at human exploration destinations to policymakers. This abstract will discuss the process of developing this SWP and ways in which the global science community can become engaged in its development.

Schmidt, Gregory↗

Impacts of Renewable Energy and Green Hydrogen Policies on Uttar Pradesh's Power Sector Future

This report is part of a broader program focused on supporting Indian states with long-term power system planning. More information about this program can be found at the National Renewable Energy Laboratory's "Supporting India's States With Renewable Energy Integration" web page at https://www.nrel.gov/international/india-renewable-energy-integration.html. The power sector in Uttar Pradesh, India's most populous state, is poised to transform over the next few decades due to a combination of national and state-level policies impacting both the supply and demand of electricity. The Government of Uttar Pradesh has policies and plans to develop in-state solar PV, pumped storage hydropower, and green hydrogen. Power system policymakers and utilities in Uttar Pradesh are faced with the challenges of planning a system that incorporates increasing amounts of renewable energy and storage resources, meets rising electricity demand due to economic development and green hydrogen production, and satisfies operational and reliability requirements. To support these various objectives, the National Renewable Energy Laboratory (NREL), RMI, and the Uttar Pradesh New and Renewable Energy Development Agency (UPNEDA) evaluated the least-cost pathways for the state's power sector through 2050. NREL developed a capacity expansion model that identifies investment and operational decisions for every year (2024-2050) for all of India, with detailed representation for the state of Uttar Pradesh, which can provide a framework for recurring planning studies. The main insights from this study can also help inform policy development and investment decisions.

08 HYDROGEN↗

Impacts of Renewable Energy and Green Hydrogen Policies on Uttar Pradesh's Power Sector Future: Additional Modeling Scenarios to Explore Hydrogen Flexibility [Slides]

This slide deck is part of a broader program focused on supporting Indian states with long-term power system planning. More information about this program can be found at the National Renewable Energy Laboratory's "Supporting India's States With Renewable Energy Integration" web page at https://www.nrel.gov/international/india-renewable-energy-integration.html. The power sector in Uttar Pradesh, India's most populous state, is poised to transform over the next few decades due to a combination of national and state-level policies impacting both the supply and demand of electricity. The Government of Uttar Pradesh has policies and plans to develop in-state solar PV, pumped storage hydropower, and green hydrogen. Power system policymakers and utilities in Uttar Pradesh are faced with the challenges of planning a system that incorporates increasing amounts of renewable energy and storage resources, meets rising electricity demand due to economic development and green hydrogen production, and satisfies operational and reliability requirements. To support these various objectives, the National Renewable Energy Laboratory (NREL), RMI, and the Uttar Pradesh New and Renewable Energy Development Agency (UPNEDA) evaluated the least-cost pathways for the state's power sector through 2050. NREL developed a capacity expansion model that identifies investment and operational decisions for every year (2024-2050) for all of India, with detailed representation for the state of Uttar Pradesh, which can provide a framework for recurring planning studies. The purpose of this slide deck is to supplement the main study (published in May 2024) with additional modeling scenarios to explore hydrogen flexibility.

08 HYDROGEN↗

Water uptake by growing cells: an assessment of the controlling roles of wall relaxation, solute uptake, and hydraulic conductance

Growing plant cells increase in volume principally by water uptake into the vacuole. There are only three general mechanisms by which a cell can modulate the process of water uptake: (a) by relaxing wall stress to reduce cell turgor pressure (thereby reducing cell water potential), (b) by modifying the solute content of the cell or its surroundings (likewise affecting water potential), and (c) by changing the hydraulic conductance of the water uptake pathway (this works only for cells remote from water potential equilibrium). Recent studies supporting each of these potential mechanisms are reviewed and critically assessed. The importance of solute uptake and hydraulic conductance is advocated by some recent studies, but the evidence is indirect and conclusions remain controversial. For most growing plant cells with substantial turgor pressure, it appears that reduction in cell turgor pressure, as a consequence of wall relaxation, serves as the major initiator and control point for plant cell enlargement. Two views of wall relaxation as a viscoelastic or a chemorheological process are compared and distinguished.

Non-NASA Center↗

Spectral analysis of resting cardiovascular variables and responses to oscillatory LBNP before and after 6 degree head dowm bedrest

A major focus of our research program is to develop noninvasive procedures for determining changes in cardiovascular function associated with the null gravity environment. We define changes in cardiovascular function to be (1) the result of the regulatory system operating at values different from 'normal' but with an overall control system basically unchanged by the null gravity exposure, or (2) the result of operating with a control system that has significantly different regulatory characteristics after an exposure. To this end, we have used a model of weightlessness that consisted of exposing humans to 2 hrs. in the launch position, followed by 20 hrs. of 6 deg head down bedrest. Our principal objective was to use this model to measure cardiovascular responses to the 6 deg head down bedrest protocol and to develop the most sensitive 'systems identification' procedure for indicating change. A second objective, related to future experiments, is to use the procedure in combination with experiments designed to determine the degree to which a regulatory pathway has been altered and to determine the mechanisms responsible for the changes.

Knapp, Charles F.↗

An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member of the (multi)gene families present and the metabolic networks that are operative. Additionally, one key to identifying physiological functions for many of these (and other) unknown genes, and their corresponding metabolic networks, awaits the development of technologies to comprehensively study molecular processes at the single cell level in particular tissues and organs, in order to establish the actual metabolic context.

NASA Program Fundamental Space Biology↗