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All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Maintaining Skeletal Health During the Mission to Mars

Understanding how the effects of long-duration spaceflight (~6-months) might increase fracture risk in the younger-aged, physically-fit astronaut is challenging. Most of our skeletal data have been acquired from long-duration astronauts, crewmembers who typically serve on 120-180 day missions aboard the International Space Station (ISS). Astronaut biomedical data are predominantly 2-d measurements from DXA scans because this is a required clinical test at Johnson Space Center. Data from these clinical tests, and some data from research studies, are what NASA evaluates to define a risk for fracture in astronauts, both during a mission and long-term health. To date, the agency considers the risk for fracture during spaceflight to be of high (severe) consequence but of low probability (<0.1%) while the risk for fracture in during long-term health to be of medium consequence (interventions available) and medium probability (<1%). These risks are considered acceptable. Notably, there are minimal data to suggest that postflight fractures in long-duration astronauts are directly due to spaceflight exposure. Analyses by NASA epidemiologists and by biomedical engineers suggest that postflight fracture incidence in astronauts is consistent with a physically-active terrestrial population with no exposure to spaceflight. The epidemiological data to-date may be considered insufficient (low # and younger-aged subjects, limited follow-up time) to assess a fracture risk with reliability. In the absence of fracture evidence to substantiate a risk, it may be more useful to maintain astronauts at baseline (preflight) level of skeletal health during a mission. This lecture will present data from astronauts that affirms that 1) the maintenance of skeletal health during the future 3-year Mars mission will require an anti-resorptive therapy and 2) the risk for fracture during long-term health cannot be defined by the DXA clinical test alone.

Sibonga, Jean↗
NASA NTRS2021

Comparing Theoretically Scaled Biomechanical Models

BACKGROUND An investigation into incorporating space suit aspects required a 50th-percentile male model which was not part of the existing dataset of models. Previously, theoretical models for 5th-percentile female and 95th-percentile male were created utilizing a scaled test subject as close as possible to the target height and weight. Scaling factors were created by taking the height ratio and applying it uniformly to the model body segments, then fine tuning to ensure the theoretical model’s height is as expected. This study was initiated to examine the existing method of isometrically scaling in OpenSim [1,2] and to create alternative methods which do not rely on an existing subject being close in height and weight to the theoretical model of interest. Generating a theoretical biomechanical model provides additional abilities without the reliance on available OpenSim models or real subjects. Gained abilities include creating different percentile models and attaining representative anthropometry for any target height/weight, such as targeting specific crew populations or gaps within the current dataset. METHODS AND RESULTS This study includes 3 methods for generating the theoretical model; utilizing the modified unscaled OpenSim Full Body Rajagopal Model (FBRM) [3,4], a dataset of scaled OpenSim models, and existing scaling factors from Dumas et al. [5]. All methods use the Anthropometric Survey of US Army Personnel (ANSUR II) [6] as an input of necessary anthropometric measurements. The following measurements are retrieved from the ANSUR II collection: mass, stature, cervicale height, acromial height, axilla height, waist height, trochanterion height, lateral femoral epicondyle height, lateral malleolus height, acromion-radiale length, radiale-stylion length, palm length, ball of foot length, bicristal breadth, bimalleolar breadth. Some of the measurements are direct segment lengths and others are utilized to derive segment lengths. Height, weight, and age ranges are the required inputs to parse the collection for a mean value of the measurements. A simple iterative process may be necessary for the output of mean mass and stature consistent with the theoretical model of interest. In some cases, one may specify exact values instead of a range but that is dependent upon whether those exact values pertain to a single subject from the ANSUR II collection. Equations from Dumas et al. were used to calculate scaling factors for the two methods that utilize OpenSim scaled and unscaled models. In the third method, Dumas’ scaling factors were used directly instead of generating our own. After scaling factors are achieved, they are applied along with the mass and segment lengths retrieved from ANSUR II in order to calculate the segment mass, Center of Mass (CoM), mass Moment of Inertia (MoI), and the joint location in the parent frame. The theoretical models from the different methods were compared to the previous existing method of isometrically scaling in OpenSim, as well as the standards found in NASA STD-3000 [7] and the NASA Human Integration Design Handbook [8]. The whole-body center of mass is the main comparison performed between the models and the standards. The body segment mass properties were also compared when possible. In some cases, the standards do not provide complete data, or the center of mass location is not provided with respect to the appropriate joint coordinate system. For a 50th-percentile male subject, results from isometric scaling in OpenSim and the method utilizing the unscaled FBRM were compared to the standards in NASA STD-3000. According to the standard, the whole-body vertical CoM location was taken from the head vertex to the CoM. The standards provide 80.2 cm for the CoM vertical component whereas isometric scaling in OpenSim and utilizing the unscaled FBRM provide 82.2 and 82.3 cm, respectively. Through definition, the whole-body CoM in the medial/lateral direction agreed across the models. Investigation is on-going to clearly identify the reference point pertaining to dorsal/ventral whole-body CoM position in standards and relate that to the theoretical models. REFERENCES [1] Delp, S.L., et al., “OpenSim: Open-source Software to Create and Analyze Dynamic Simulations of Movement”, IEEE Transactions on Biomedical Engineering, (2007). [2] Seth, A., Hicks J.L., Uchida, T.K., Habib, A., Dembia, C.L., Dunne, J.J., Ong, C.F., DeMers, M.S., Rajagopal, A., Millard, M., Hamner, S.R., Arnold, E.M., Yong, J.R., Lakshmikanth, S.K., Sherman,n M.A., Delp, S.L. OpenSim: Simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement. Plos Computational Biology, 14(7). (2018) [3] R. K. Huffman, W. K. Thompson, C. A. Gallo, L. J. Quiocho, “Improvement of Scaling and Inverse Kinematic Results with Additional Upper Body Joints Added to Opensim Rajagopal Model”, NASA Human Research Program Investigator’s Workshop, (2019). [4] Huffman R.K., Thompson W., Gallo C., “Modified OpenSim Rajagopal Full Body Model”, New Technology Report, MSC-26872-1. (August 2020). [5] Dumas R., Cheze L. and Verriest J., 2007. “Adjustments to McConville et al. and Young et al. body segment inertial parameters”. Journal of Biomechanics 40, pp. 543-553 [6] Gordon C.C., 2012 “Anthropometric Survey of U.S. Army Personnel: Methods and Summary Statistics”, US Army Natick Soldier RD&E Center. [7] NASA STD-3000/REV-B, 1995. “The Man-System Integration Standards” [8] NASA/SP-2010-3407/REV-1, 2014. “The Human Integration Design Handbook (HIDH)”

F N Matari↗
NASA NTRSDate not supplied

NASA Commercial Crew Program and Medical Operational Challenges

This abstract is submitted as part of the USSPACECOM Command Surgeon’s panel demonstrating the medical capabilities and challenges involved in human space flight support operations. BACKGROUND: NASA embarked on the Commercial Crew Program to launch astronauts into low-earth orbit from US soil and dock with the International Space Station (ISS). The eventual industry providers selected were SpaceX (SpX) and Boeing. These commercial transportation systems are vital to ensure crew availability on ISS for research and discovery. OVERVIEW: NASA/SpaceX Demo-2 (DM2) mission launched from the Kennedy Space Center in 2020 as the historic first crewed test-flight of the Crew Dragon spacecraft with two NASA Astronauts onboard. DM2 represented the first flight in 9-years from US soil since STS-135 in 2011. The 63-day mission ended with splashdown in the Gulf of Mexico, the first US water recovery in 45-years since Apollo-Soyuz. Validation of system hardware and operations allowed four-person crews to launch on subsequently missions (Crew-1, Crew-2, Crew-3, Crew-4, Crew-5 to date), which included International Partner crewmembers. DISCUSSION: A multitude of operational, training, medical, and technical issues needed to be addressed between NASA Medical Operations, the commercial provider SpaceX, and the Department of Defense. These included Flight rule development, occupant protection, pressurized suit testing, communication plans during mission phases, and emergency simulations for supporting Flight Surgeons and Biomedical Engineers. In providing crew experience with expected launch and entry G-force profile, Centrifuge training was established. Preventive health measures via the Health Stabilization Program were especially vital during the global COVID-19 pandemic. Unique aspects arise for SpX Dragon parachute splashdown and shipboard recovery operations in the Atlantic Ocean and Gulf of Mexico. The new Commercial Crew Program is indeed a wonderfully challenging and exciting era for human spaceflight.

Joseph Dervay↗
NASA NTRSDate not supplied

Intercalation and Exfoliation of Hexagonal Boron Nitride

Innovators at NASA's Glenn Research Center have made several breakthroughs in treating hexagonal boron nitride (hBN) nanomaterials, improving their properties to supplant carbon nanotubes in many applications. These advances have hBN nanomaterials set to transform applications such as heat sinks, electrical insulators, lightweight piezoelectric polymers for satellites and unmanned aerial vehicles, ceramic composites for jet engines, biomedical components, and radiation shielding technology.

Hexagonal Boron Nitride↗
NASA NTRSDate not supplied

NASA Commercial Crew Program and Medical Operational Challenges

BACKGROUND: NASA embarked on the Commercial Crew Program to launch astronauts into low-earth orbit from US soil and dock with the International Space Station (ISS). The eventual industry providers selected were SpaceX (SpX) and Boeing. These commercial transportation systems are vital to ensure crew availability on ISS for research and discovery. OVERVIEW: NASA/SpaceX Demo-2 (DM2) mission launched from the Kennedy Space Center in 2020 as the historic first crewed test-flight of the Crew Dragon spacecraft with two NASA Astronauts onboard. DM2 represented the first flight in 9-years from US soil since STS-135 in 2011. The 63-day mission ended with splashdown in the Gulf of Mexico, the first US water recovery in 45-years since Apollo-Soyuz. Validation of system hardware and operations allowed four-person crews to launch on subsequently missions (Crew-1, Crew-2, Crew-3, Crew-4, Crew-5 to date), which included International Partner crewmembers. DISCUSSION: A multitude of operational, training, medical, and technical issues needed to be addressed between NASA Medical Operations, the commercial provider SpaceX, and the Department of Defense. These included Flight rule development, occupant protection, pressurized suit testing, communication plans during mission phases, and emergency simulations for supporting Flight Surgeons and Biomedical Engineers. In providing crew experience with expected launch and entry G-force profile, Centrifuge training was established. Preventive health measures via the Health Stabilization Program were especially vital during the global COVID-19 pandemic. Unique aspects arise for SpX Dragon parachute splashdown and shipboard recovery operations in the Atlantic Ocean and Gulf of Mexico. The new Commercial Crew Program is indeed a wonderfully challenging and exciting era for human spaceflight.

Joseph P Dervay↗
DOE OSTI2025

Extending wire-arc directed energy deposition using non-gravity aligned (NGA) torch methods

For standard Additive Manufacturing (AM) processes, traditional path planning typically relies on a 2.5-dimensional approach. In wire-arc directed energy deposition (DED), commonly referred to as wire-arc additive manufacturing (WAAM), this 2.5D approach inherently limits final near net shape due to the stair-step effect and restricts the maximum overhang angle achievable without part degradation. To achieve better near net shape and part quality, a 3D planning approach that modulates the tool tip position and angle without process changes is demonstrated in components containing up to 105° of unsupported overhang. The experimental methods are validated with half and fully enclosed cylinder sections containing 90° of overhang. The non-gravity aligned methods are then applied to a commercial WAAM system for a composite tool mold demonstrator part. As a result, the methods developed in this paper enable expansion of WAAM system capabilities to parts containing large overhangs without compromising the net shape or material structure of the resulting parts and without the need for a part positioner.

Additive manufacturing↗
DOE OSTI2025

Modeling Protein–Protein and Protein–Ligand Interactions by the ClusPro Team in CASP16

ABSTRACT In the CASP16 experiment, our team employed hybrid computational strategies to predict both protein–protein and protein–ligand complex structures. For protein–protein docking, we combined physics‐based sampling—using ClusPro FFT docking and molecular dynamics—with AlphaFold (AF)‐based sampling, followed by AF‐based refinement. Our method produced numerous high‐accuracy complex models, including cases where AF alone failed, underscoring the critical role of physics‐based sampling alongside deep learning‐based refinement. For protein–ligand docking, we integrated the ClusPro LigTBM template‐based approach with a machine learning‐based confidence model for rescoring. The method preserves conserved interaction fragments derived from homologous complexes, followed by local resampling using physics‐based sampling and a diffusion model. Our template‐based strategy achieved a mean lDDT‐PLI of 0.69 across 233 targets, which was highly competitive. These results demonstrate that combining physics‐based modeling with AI‐driven refinement can significantly enhance the accuracy of both protein–protein and protein–ligand structure predictions.

Ashizawa, Ryota [Department of Applied Mathematics↗
DOE OSTI2024

The Influence of Alkyl Spacers and Molecular Weight on the Charge Transport and Storage Properties of Oxy‐Bithiophene‐Based Conjugated Polymers

Abstract Conjugated polymers (CPs) with polar side chains can conduct electronic and ionic charges simultaneously, making them promising for bioelectronics, electrocatalysis and energy storage. Recent work showed that adding alkyl spacers between CP backbones and polar side chains improved electronic charge carrier mobility, reduced swelling and enhanced stability, without compromising ion transport. However, how alkyl spacers impact polymer backbone conformation and, subsequently, electronic properties remain unclear. In this work, we design two oxy‐bithiophene‐based CP series, each featuring progressively extended alkyl spacer lengths and two distinct molecular weight (MW) distributions. Using operando characterisations, we evaluate the (spectro)electrochemical and swelling properties of the polymer thin films, and their performance in organic field‐effect transistors and organic electrochemical transistors. Surprisingly, alkyl spacers negatively impact the hole mobility of our polymers, with higher MW amplifying this effect. Using molecular dynamics simulations, we show that it is thermodynamically favourable for adjacent non‐polar alkyl spacers to aggregate in polar electrolytes, leading to backbone twisting. Further spectroscopic measurements corroborate this prediction. Our findings demonstrate the active interactions between side chain structure, MW and electrolyte/solvent polarity in influencing polymer performance, underscoring the importance of considering solvation environment effects on polymer conformation when designing new mixed conducting CPs for electrochemical applications.

Yu, Hang [Department of Physics and Centre for Pro↗
DOE OSTI2026

Structure-function analysis of the FCRL5–IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG

The Fc region of therapeutic IgG antibodies is often engineered to remove or “silence” Fc effector functions, but it remains unclear whether these mutations eliminate all Fc-mediated effector activity. Human Fc receptor-like 5 (FCRL5/FcRH5) is a low-affinity IgG Fc receptor expressed on B cells and is an actively pursued antibody target in multiple myeloma. Here, we show that common Fc function-silencing mutations do not impair FCRL5-mediated activity and therefore attenuate, rather than eliminate, Fc effector function. The crystal structure of the FCRL5-IgG1 Fc complex, solved at 3.4 Å resolution, revealed that FCRL5 binds IgG1 Fc in a 1:1 complex through a binding mode distinct from that of classical Fcγ receptors, explaining why mutations that attenuate Fc effector function spare FCRL5 binding. Fc-engineered antibodies that selectively engage FCRL5 inhibited B cell receptor-induced Ca 2+ flux in FCRL5-expressing B cells. These findings demonstrate that Fc-attenuated therapeutic IgG retains the ability to engage FCRL5, identifying an unappreciated pathway for B cell modulation.

Herpers, Bart M. [Department of Biomedical Enginee↗
NASA NTRS2024

Biomedical Research for Human Spaceflight

This invited presentation will offer an overview of the biomedical research – both from a biomedical sciences and engineering perspective – of human physiology and performance during spaceflight. Focused on the unique expertise within the Biomedical Sciences Branch, NASA Johnson Space Center, the talk will elucidate the critical role of biomedical laboratories in synergistic activities in clinical sciences, space physiology, applied research, technology development, and operational support for human space exploration. Together, the efforts within this branch play a crucial role in supporting astronauts' health, performance, and safety. The branch Scientists, Researchers, and Engineers conduct biomedical research in flight on board the International Space Station and on-earth space environment analogs. This dual approach allows for a nuanced understanding of the effects of micro- and planetary gravitation fields on human physiology and the assessment of potential clinical and biomedical interventions (countermeasures) to mitigate astronaut clinical and performance decrements. The talk aims to underscore the synergistic collaborative efforts of biomedical engineers, physiologists, clinicians, and computational researchers, emphasizing these experts' pivotal role in advancing human spaceflight's frontiers.

Biomedical Research↗
DOE OSTI2025

A Route to Design Novel Functional Peptides by Applying a Denoising Diffusional Model to mRNA Display Libraries

In vitro directed evolution techniques, such as mRNA display, enable peptide ligand discovery and optimization. However, physical libraries that rely on a genetic code can only search a small fraction of sequence space due to inherent biases in the genetic code and experimental limitations. To address this challenge, denoising diffusion implicit models (DDIMs) are applied to generate novel peptide ligands against B‐cell lymphoma extra‐large (Bcl‐x L ), a key cancer target. Starting with high‐throughput sequencing data from previous selections, a DDIM is trained to produce novel sequences with high affinity binding. Experimental validation confirms that most generated sequences are functionally equivalent to the original library members for Bcl‐x L binding and demonstrated comparable binding kinetics and affinity relative to the wildtype and nearest original neighbors. Importantly, this approach generated rare sequences not easily accessible via mutation and directed evolution. These results indicate that DDIMs can complement and expand directed evolution data, efficiently exploring underrepresented regions of sequence space. This approach provides a broadly applicable framework for accelerating ligand discovery and optimizing molecular properties across diverse targets.

Qi, Pearl [Mork Family Department of Chemical Engi↗
DOE OSTI2025

Magnetically responsive nanocultures for direct microbial assessment in soil environments

Cultivating microorganisms in native-like conditions is vital for bioprospecting and accessing now unculturable species. However, there remains a gap in scalable tools that can both mimic native microenvironments and enable targeted recovery of microbes from complex settings. Such approaches are essential to advance our understanding of microbial ecology, predict community functions, and discover previously unidentified biotherapeutics. We present magnetic nanocultures—a high-throughput microsystem for isolating and growing environmental microbes under near-native conditions. These nanoliter-scale bioreactors are encapsulated in semipermeable membranes that form magnetic polymeric microcapsules using iron oxide nanoparticles within polydimethylsiloxane-based shells. This design offers mechanical stability and magnetic actuation, enabling efficient retrieval from soil-like environments. The nanocultures are optimized for optical and biological properties to support microbial encapsulation, growth, and sorting. Our study demonstrates the feasibility of using magnetically responsive microenvironments to cultivate elusive microbes, offering a promising platform for bioprospecting previously uncultured or unknown microbial species.

Usman, Huda [Department of Chemical Engineering, C↗
DOE OSTI2025

Freestanding BaTiO 3 ‐Au Vertically Aligned Nanocomposite toward Flexible Multi‐Sensing Platform

Abstract Flexible and wearable sensors show enormous potential for personalized healthcare devices by real‐time monitoring of an individual's health. Typically, a single functional material is selected for one sensor to sense a particular physical signal while multiple materials will be selected for multi‐mode sensing. Vertically aligned nanocomposites (VANs) have recently demonstrated various material combinations and novel coupled multifunctionalities that are hard to achieve in any single‐phase material alone, including multiphase multiferroics, magneto‐optic coupling, and strong magnetic and optical anisotropy. Integrating these novel VANs into wearable sensors shows enormous potential in multi‐mode sensing owing to their multifunctional nature. In this work, the transfer of VANs onto polydimethylsiloxane as a novel flexible chemical and pressure sensor is demonstrated. For this demonstration, the classical BaTiO 3 ‐Au VAN with combined plasmonic and piezoelectric properties is used to demonstrate a multi‐sensing mechanism. A thin water‐soluble buffer of Sr 3 Al 2 O 6 serves as a buffer layer for the epitaxial growth and transfer process. The electrical output based on the piezoelectric responses and identifying 4‐mercaptobenzoic acid by surface‐enhanced Raman spectroscopy reveal great potential for free‐standing VANs in a wearable multifunctional sensing platform.

Tsai, Benson Kunhung [School of Materials Engineer↗
DOE OSTI2026

Towards libraries of different ultrasmall amorphous silica cage topologies

Cage topology controlled at the nanometer length scale is expected to enable original functionalities, e.g., in catalysis and therapeutics. Cages are fundamental structural motifs of clathrates and their topological duals, Frank-Kasper phases, and are constituents of mesoporous silica frameworks. However, with one exception, they have not been synthesized as discrete particles. By varying reactant ratios of surfactant, oil, and silane, we report the discovery of 5(12)6(2) and 5(12)6(8) amorphous silica polyhedra, each coexisting with the previously identified 5(12) cage, using combined cryo-transmission electron microscopy (cryo-TEM) and single-particle reconstruction (SPR). Notably, the 5(12)6(8) polyhedron represents a topology not previously observed in mesoporous silica frameworks. Control over structural features is demonstrated, and insights into cage formation mechanisms are provided. Structural outcomes are summarized in a ternary morphology diagram alongside prior results, bridging serendipitous discovery and intentional design of silica cages displaying a level of control over silica polymerization rivaling nature.

Jang, Dong June [Department of Materials Science a↗
DOE OSTI2025

Mechanical and Light Activation of Materials for Chemical Production

Abstract Mechanical expansion and contraction of pores within photosynthetic organisms regulate a series of processes that are necessary to manage light absorption, control gas exchange, and regulate water loss. These pores, known as stoma, allow the plant to maximize photosynthetic output depending on environmental conditions such as light intensity, humidity, and temperature by actively changing the size of the stomal opening. Despite advances in artificial photosynthetic systems, little is known about the effect of such mechanical actuation in synthetic materials where chemical reactions occur. It is reported here on a hybrid hydrogel that combines light‐activated supramolecular polymers for superoxide production with thermal mechanical actuation of a covalent polymer. Superoxide production is important in organic synthesis and environmental remediation, and is a potential precursor to hydrogen peroxide liquid fuel. It is shown that the closing of pores in the hybrid hydrogel results in a substantial decrease in photocatalysis, but cycles of swollen and contracted states enhance photocatalysis. The observations motivate the development of biomimetic photosynthetic materials that integrate large scale motion and chemical reactions.

Đorđević, Luka [Department of Chemical Sciences Un↗