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NASA NTRSDate not supplied

Recent Advancements in the PATO Material Response Code

Introduction: Predicting the complicated multiphysics phenomena during atmospheric entry requires high-fidelity modeling tools to refine estimates of mission risks during entry. To this end, new capabilities are being added to the Porous-material Analysis Toolbox based on OpenFOAM (PATO) [1,2,3]. PATO is an open-source software for Computational Material Response (CMR) of reactive porous materials submitted to high-temperature environments. The objective of this work is to highlight current efforts to add to and improve upon the modeling capabilities of PATO. These include efforts to loosely couple PATO with other discipline specialized codes including hypersonic Computational Fluid Dynamics (CFD), to assess the interaction effects between pyrolysis gas blowing and the boundary layer, and Computational Solid Mechanics (CSM), to address modeling of mechanical erosion. Other refinements include surface phenomena modeling capabilities to address the effects of silicone-based coatings applied to the TPS during flight preparation, and a unified multiphase solver for a mixed porous-material and plain-fluid domain. Coupling CMR with CFD (CMR/CFD): A loose coupling between PATO and the Data Parallel Line Relaxation (DPLR) [4] CFD code has been achieved by making use of a blowing boundary condition at the heatshield surface available in DPLR. Starting with heat flux estimates with no pyrolysis gas blowing at the surface, blowing gases are computed by the CMR and passed to the CFD such that aerothermal properties of the environment can be recomputed for a new CMR computation. This leads to an iterative process which is supplemented with an estimate of the radiative heat flux using the Nonequilibrium air radiation (NEQAIR) [5] program. The entire iterative process is illustrated in Figure 1. This coupling strategy has been utilized in computing the MSL material response. The goal is to compare the coupled CMR/CFD results with material response results obtained using traditional blowing corrections. Coupling CMS with CMR: A mechanical erosion model is currently being implemented in PATO to account for the additional mass removal induced by high shear conditions. The modeling process at each timestep consists of updating the mechanical properties as a function of temperature and computing the stress tensor and displacement fields of the material. Then, a failure criteria model determines the regions in which the stress exceeds the ultimate strength values resulting in mesh movement to account for mass removal. This model allows the material response simulation to compute the recession due to both oxidation and shear-induced erosion. The model is demonstrated by computing material response of sphere-cone arc jet samples. Surface Modeling Capabilities: NuSil, a silicone-based coating, was sprayed onto the MSL and Mars 2020 heatshields to mitigate shedding of phenolic dust. To better understand the effects of the NuSil coating on the material response, a novel model has been implemented in PATO. In this model, the equilibrium of the charred NuSil surface is modeled as pure silica, and a constant offset, inspired by the classical spallation model, is added to the the char blowing rate and wall enthalpy to reproduce HyMETS experimental results. The model has also been used to estimate the 3D material response of the MSL heatshield [6]. Unified Solver: In addition to the iterative loose coupling approach mentioned above, a multiphase unified solver is being developed to couple the environment (plain-fluid phase) and the porous-material phase. The solver is based on the volume averaged conservation of mass, momentum, and energy for the macroscale with closure models which include microscale effects through effective physicochemical properties. The unified solver has been used to compute flow through a porous plug and solve the Beavers and Joseph problem [7]. Since the strong coupling between phases is inherent to this solver, modeling assumptions present in other coupling methods of material response are mitigated. This strategy also makes it feasible to capture the competition between surface and volume ablation in the same computational domain, which is usually not possible with other coupling approaches.

Thermal Protection Systems↗
NASA NTRS2021

Topical: Stem Cell-Based Tissue Regenerative Health in Space

The maintenance of healthy adult tissues in mammals requires a complex homeostasis of molecular, cellular, tissue, and metabolic processes which are fundamentally different from the development and aging processes that bookend life. Cellular homeostasis in the adult requires molecular maintenance and repair of non-dividing cells such as cardiomyocytes and neurons, but also stem cell-based tissue regeneration via direct replacement of cell loss, such as in the blood, immune system, bone, skin, liver, intestine, and other tissues. Because stem cell-based tissue regenerative health requires constant proliferation and differentiation of stem cell progenitors in the bone marrow, and other adult stem cell niches, it is uniquely sensitive to the stresses of spaceflight including exposure to space radiation and mechanical unloading in microgravity. A key central hypothesis in this field is that those spaceflight stress factors can have profound negative effects on long-term tissue regenerative health mediated by adult stem cells, and that unmitigated, they may lead to premature tissue aging and functional failure. Specifically, it is thought that mechanical unloading due to lack of weight-bearing in space reduces mitogenic mechanotransduction necessary to promote adult stem cell proliferation and differentiation, and that space radiation can also lead to activation of cell cycle arrest mechanisms, further reducing adult stem cell proliferation. These hypotheses are being tested in low earth orbit(LEO)using a variety of cellular and whole organism tissue model systems, suggesting that spaceflight consistently interferes with stem cell tissue regenerative processes such as in mammalian embryoid bodies, regenerating newt tails, and mouse bone marrow hematopoietic and osteoprogenitor cells. Furthermore, potential molecular mechanisms integrating both space radiation and mechanical disuse via oxidative stress and the cell cycle inhibitor Cdkn1aare now under study using single cell (scRNAseq) expressome analysis of bone marrow osteoprogenitors, both under stretch loading, and spaceflight conditions including in various mouse transgenic null backgrounds relevant to these mechanisms. Future work in the area of tissue regenerative health in space for the coming decade should seek to understand the responses the various tissue regenerative stem cell niches in humans and relevant model organisms, and how they respond to long-term exposure to the space environment. Special emphases of future work should be on how regenerative deficits in whole-organism stem cell niches may lead to tissue degeneration and premature aging, and on the long-term proliferation and differentiation of stem cell derived tissue organoid models in the deep space environment outside of LEO.

Eduardo A C Almeida↗
DOE OSTI2022

Origin of Ferroelectric Phase Stabilization via the Clamping Effect in Ferroelectric Hafnium Zirconium Oxide Thin Films

The presence of the top electrode on hafnium oxide-based thin films during processing has been shown to drive an increase in the amount of metastable ferroelectric orthorhombic phase and polarization performance. This “Clamping Effect,” also referred to as the Capping or Confinement Effect, is attributed to the mechanical stress and confinement from the top electrode layer. However, other contributions to orthorhombic phase stabilization have been experimentally reported, which may also be affected by the presence of a top electrode. In this study, it is shown that the presence of the top electrode during thermal processing results in larger tensile biaxial stress magnitudes and concomitant increases in ferroelectric phase fraction and polarization response, whereas film chemistry, microstructure, and crystallization temperature are not affected. Through etching experiments and measurement of stress evolution for each processing step, it is shown that the top electrode locally inhibits out-of-plane expansion in the HZO during crystallization, which prevents equilibrium monoclinic phase formation and stabilizes the orthorhombic phase. This study provides a mechanistic understanding of the clamping effect and orthorhombic phase formation in ferroelectric hafnium oxide-based thin films, which informs the future design of these materials to maximize ferroelectric phase purity and corresponding polarization behavior.

36 MATERIALS SCIENCE↗
NASA NTRS2011

Contribution of Spaceflight Environmental Factors to Vision Risks

The risk of visual impairment and elevated intracranial pressure as a result of low-earth orbit microgravity exposure has directed our attention and research efforts to the eye. While the alterations observed in astronauts returning from long duration missions include vision and neuroanatomical changes observed by non-invasive methods, other effects and subsequent tissue responses at the molecular and cellular level can only be studied by accessing the tissue itself. As a result of this need, several studies are currently taking place within the Human and Health Countermeasures Element (HHC) that use animal models for eye research. The rodent eye has many similarities to the human eye, and both rats and mice have historically been used as models of human eye disease, aiding in the identification of the disease genes, elucidation of mechanisms of disease, as well as in the assessment of therapeutic treatments. These studies attempt to answer two central questions in the etiology of possible vision alterations in the environment of space exploration missions. The first is: what effects and response mechanisms take place in the different eye structures at the cellular and molecular level? The second question is directed to elucidate the contribution of the various environmental stressors (radiation, nutrition, fluid shift) to these effects. Collaborative approaches with internal and external investigators have allowed performing these studies in a most cost-effective fashion, providing preliminary data and laying the bases for testing further hypotheses in future and specifically designed animal experiments. From a study centered on the radioadaptive response in mice, we have learned that the retina responds to low and high dose gamma radiation by elevating antioxidant-related genes at early time points (4hrs) and that this response returns to control levels after 1 day post-irradiation. We are expanding this research with another collaborative study that investigates the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in rat eyes. All main eye structures will be analyzed in this study: retina, lens and cornea. A study in collaboration with the Space Human Factors and Habitability Element (SHFH) investigates the effects of lunar dust exposure on the rat cornea. It is anticipated that common underlying oxidative stress mechanisms of damage may be observed as a result of these three stressors: radiation, nutritional iron and lunar dust. The contribution of fluid shift is addressed by a study using rats subjected to hindlimb suspension. The hypothesis to be tested in this study is that the mechanical stress imparted by the pressure differential across the optic disc and lamina cribosa will impact oxygenation (therefore causing oxidative stress and hypoxia) and cell survival. This study also includes the assessment of two nutritional antioxidant countermeasures: epigallocatechin gallate (green tea) and resveratrol. Finally, as a result of two successful tissue sharing efforts, we are proceeding with the analysis of eye samples of mice aboard two shuttle missions: STS-133 and STS-135. Results from the STS-133 study are presented in an independent abstract. Briefly, the results show that spaceflight represents a source of environmental stress that directly translates into oxidative and cellular stress in the retina. Similar analysis is also planned for the cornea. These samples add large value to our current vision research as they provide data on the direct effects of low-earth orbit spaceflight on eye structures and physiology.

Zanello, Susana B.↗
NASA NTRSDate not supplied

Cleanroom Microbes Survive Drying, Vacuum, and Proton Irradiation

Introduction : The goal of planetary protection at NASA is to mitigate the risk of contaminating sensitive target bodies with biological life. While many cleaning procedures have been put in place to reduce bioburden on spacecraft, microbes are experts at evolving to survive harsh conditions. Specifically, the dry, low-nutrient environment of a cleanroom (commonly used for assembly of spacecraft) can represent an environment where extremophiles can survive. Methods : Scientists at NASA MSFC wished to gather a snapshot of the microbial population within a variety of cleanrooms on site. A study was undertaken to collect air, surface, and floor samples from clean-rooms and isolate unique morphologies. From this study, 95 isolates were collected and saved in a microbial library. About 86% of these were identified at least to a genus level. Following identification, 24 microbes were selected, based on a literature review, as potential extremophiles. These were grown in liquid cultures, diluted to a set optical density, washed with water, and then applied to a sterilized Kapton coupon. Droplets were allowed to dry overnight in a biosafety cabinet. Coupons were then installed in a pelletron and pumped down to high vacuum (~1E-6 Torr). Samples were then subjected 100 keV protons at a fluence of 2x10 15 p+/cm 2 up to 4x10 15 p+/cm 2 . Following exposure, samples were returned to the microbiology lab where they were pro-cessed by submerging in water, vortexing, and then plating either droplets or spread plates. Recovery data collected was qualitative with a ranking or +, minor, or – for growth. Some selected radiotolerant strains were sequenced using the Illumina sequencing platform. The resulting genomes were annotated with the Rapid Annotations using Subsystems Technology (RAST) server and analyzed for conserved and unique stress response relevant genomic signatures to identify clues related to specific tolerances. Results and Discussion : After five rounds of proton radiation, we narrowed our isolates to five, non-spore forming bacteria that demonstrated survival: Arthrobacter koreensis, Paenarthrobacter nitroguajacolicus, Mycetocola manganoxydans , and an Erwinia sp. Furthermore, we exposed these four microbes to 254 nm wavelength light at an intensity of 80 W/m 2 at a distance of ~18 cm for 10 minutes. Only A. koreensis demonstrated survival following UV exposure. Finally, we performed whole genome sequencing on the four strains to look for genetic markers of stress resistance. When we compared the genomes of the four strains, we found that genes coding for GGDEF and EAL domains with PAS/PAC sensors were only found in A. koreensis . These domains, modulated by PAS/PAC sensors, are hypothesized to facilitate survival under drying, desiccation, and proton irradiation. Drying and Desiccation : PAS domains sense hydration changes and modulate GGDEF and EAL domain activity to adjust c-di-GMP levels, enhancing resistance to desiccation. For instance, in Pseudomonas aeruginosa , the PAS domain of RbdA modulates activity under varying hydration conditions, affecting stress responses [1]. Proton Irradiation : Proton irradiation causes oxidative stress, leading to ROS generation. PAS domains detect this stress and modulate GGDEF and EAL domains to manage oxidative stress responses. In Shewanella , EAL domain proteins modulated by PAS sensors help bacteria adapt to extreme conditions [2]. These genes upregulate other stress response genes, protecting membrane function, protein stability, DNA repair, and antioxidant defenses. The modulation of c-di-GMP by PAS domains is crucial for bacterial adaptation to stress conditions, enabling dynamic physio-logical adjustments [3]. Understanding these mechanisms provides insights into bacterial stress responses and strategies for controlling bacterial growth [4]. Conclusions : These findings indicate that clean-rooms harbor extremophile microbes that may be able to survive conditions in deep space. Furthermore, while we identified certain stress-response genes that may be at least partly responsible for the phenotypes observed in this study, there are likely unidentified genes or characteristics about A. koreensis , and other bacteria, that may allow them to survive in harsh environments. Future studies will focus on identifying these unknown genes and characteristics, further elucidating the mechanisms of extremophile survival and potentially informing the development of new biotechnologies for space exploration and other extreme environments.

Chelsi Cassilly↗
NASA NTRS2018

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

redox siggnalin↗
NASA NTRS2016

Effects of Hindlimb Unloading and Ionizing Radiation on Murine Gene Expression in Skin and Bone

Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The underlying mechanisms of spaceflight-induced bone loss and the possible influences of both microgravity and radiation are not fully understood although emerging evidence suggests that these two factors may interact to result in increased bone loss. Previously, gene expression analysis of hair follicles from astronauts, as well as skin from space-flown mice, revealed changes in the expression of genes related to DNA damage and oxidative stress responses. These results resemble the responses of bone to spaceflight-like radiation and simulated weightlessness by hindlimb unloading (HU). Hence in this study, we initiated studies to determine whether skin can be used to predict the responses of bone to simulated microgravity and radiation. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR). To investigate the effects of irradiation andor HU on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated) (CT), hindlimb unloading (HU), 56Fe radiation (IR) and both HU+IR. Animals were euthanized 11 days post-IR, and results were analyzed by 1-way ANOVA. In skin samples, Cdkn1a was decreased to the same extent in HU and HU+IR (47 of CT). In addition, HU reduced FoxO3 expression (46 of CT) and IR increased Gadd45g expression 135 compared CT in skin. But in bone, HU increased FoxO3 expression 31 compared the level of CT. These results suggest that radiation and simulated weightlessness regulated simliar oxidative stress and cell cycle arrest genes in both skin and bone, although the time course and direction of changes may differ. This research may lead to the development of a relatively simple diagnostic tool for bone loss with the advantage that hair follicles and skin are relatively easy to acquire from subjects.

Terada, Masahiro↗
NASA NTRS2015

Beneficial Effects of Metabolic Supression for Adoptation and Survival in Space Environment

NASA in its plans to send humans to distant destination such as Mars faces the health and physiological performance problems caused by microgravity and space radiation. While most of the environmental conditions in spacecraft during flight can be made to mimic terrestrial conditions, microgravity cannot yet be managed. This space environmental factor has a major impact on the body’s biological system forcing alterations, in order to adapt to this new environment. Most space flight and ground-based studies suggest that prolonged exposure to microgravity leads to significant skeletal muscle atrophy, bone loss, and results in suppression of total metabolism. Due to microgravity, unloaded crewmembers lose up to 1.5% of their skeletal mass and 1.8% of bone strength each month during ISS missions. Remarkably many animals, including human-size bears, which are largely inactive during the 6 to 8 months of hibernation, show no loss in bone mass and much less muscle atrophy than would be anticipated over such a prolonged period of physical inactivity. This suggests that while in a suppressed metabolic state animals have unique natural mechanisms to prevent muscle disuse and bone atrophy. The molecular mechanisms underlying these important adaptations are not yet known. Radiation exposure is the second health hazard encountered during spaceflight that can cause radiation sickness, cancer or death. This study provides new evidence that metabolic activity levels play a critical role in radioprotection. Metabolic suppression, as an adaptive response of cells to minimize damage caused by radiation, enables cells to reduce cellular dysfunction and damage, and prolong their survival despite persistent oxidative stress. Thus mechanistic understanding of metabolism offers a means for sustaining astronauts in long-duration missions. The ultimate goals of this study are to demonstrate that induced metabolic suppression in animals and humans will profoundly reduce their sensitivity to the damaging effects of radiation and microgravity as well as other kinds of stresses caused by spaceflight. The beneficial effects of suppressed metabolism induced by different factors such as temperature, nutrition, and medications, will not only mitigate the most detrimental hazards of spaceflight but also radically reduce mission life support requirements and spaceflight logistics.

Galicia, E.↗
NASA NTRS2018

Space Radiation Induces Long Term Impact on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species

Space radiation can damage the cardiovascular system and thus is an important health risk factor for astronauts during long-term space missions. We utilized publicly available transcriptomic data through NASA's GeneLab platform (genelab.nasa.gov) to determine cardiovascular system response to space radiation. GeneLab is an open repository that houses all NASA related omics experiments including on the International Space Station (ISS) and related radiation ground studies. We analyzed 3 datasets from GeneLab: GLDS-117 and GLDS-109, which are ground studies of cardiomyocytes followed-up for 28 days after exposure to 90cGy of proton at 1GeV and 15cGy of 56Fe at 1GeV; and GLDS-52, human endothelial cells (HUVECs) that were cultured for 10 days on the ISS. The ground studies were designed to characterize the long-term impact following space irradiation on cardiomyocytes for 5 different time points up to 28 days after irradiation. Our analysis was guided by the hypothesis that there are common persistent molecules affecting the cardiovascular system due to radiation effects during spaceflight. Endothelial cells are known to directly regulate the development and activity of cardiomyocytes, and thus their response to spaceflight should be highly correlated with cardiomyocytes. To investigate our hypothesis, we identified the molecular pathways that were modified for all time points compared across both radiation on the ground and the pathways found in HUVECs flown in the ISS. We found the following key results related to the cardiovascular systems: 1) space radiation downregulate ROS functions; and 2) the key/driving genes: FYN, LCK, AKT1 are upregulated and LYN and FOS are downregulated with FYN being the central driver/hub for the cardiovascular response to space radiation. It is worth noting the activation of FYN is a key event which prevents cardiac cell death and ROS production. From our study we thus hypothesize that a feedback loop occurs from the oxidative stress caused by space radiation that upregulates FYN which in turn reduces ROS levels and thus ROS pathways, preventing cardiomyocyte and endothelial cell death and thus protecting the cardiovascular systems. We believe that this is a novel mechanism for space radiation induced cardiovascular risk directly linking radiation ground studies to spaceflight

Beheshti, Afshin↗
DOE OSTI2023

Identification of small-molecule protein–protein interaction inhibitors for NKG2D

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ + , and CD8 + T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, in this study, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein–protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure–activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2000

Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

Radhakrishnan, Krishnan↗
NASA NTRS2018

Neutrophil to Lymphocyte Ratio: A Prognostic Indicator for Astronaut Health

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count data collected from astronauts and rodents that have flown for short- and long-term missions on board the International Space Station (ISS) was repurposed to determine the NLR pre-, in-, and post-flight. The results displayed that the NLR progressively increased during spaceflight in both human and mice, while a spike in the NLR was observed at post-flight landing, suggesting stress-induced factors may be involved. In addition, the ground-based chronic microgravity analog, hindlimb unloading in mice, indicated an increased NLR, along with induced myeloperoxidase expression, as measured by quantitative (q)PCR. The mechanism for increased NLR was further assessed in vitro using the NASA-developed rotating wall vessel (RWV) cell culture suspension system with human WBCs. The results indicated that simulated microgravity led to increased mature PMN counts, NLR profiles, and production of reactive oxygen species (ROS). Collectively, these studies show that an increased NLR is observed in spaceflight missions, and in chronic microgravity-analog simulation in mice, and that this effect may be potentiated by the oxidative stress response in blood cells under microgravity conditions. Furthermore, these results suggest that a disrupted NLR profile in spaceflight may further disrupt immune homeostasis, potentially causing chronic immune-mediated inflammatory diseases. Thus, we propose that the health status of astronauts during short- and long-term space missions can be monitored by their NLR profile, in addition to utilizing this measurement as a tool for interventions and countermeasure development to restore homeostatic immunity.

biomarker↗
DOE OSTI2023

A Physics-Based Data-Driven Approach for Modeling of Environmental Degradation in Elastomers

Abstract Elastomers are now commonly used in a number of industries, including aerospace, structure, transportation, shipbuilding, and automotive, due to their excellent workability, formability, and flexibility. During their activity, elastomers are subjected to harsh environmental conditions, which decreases their resilience. False predictions made early in their lives can have major financial and environmental implications. Elastomers’ performance and properties, such as strength, durability, and density, are influenced by chemical changes in these materials, known as degradation, which occurs over time. This process can alter the morphology of a polymer matrix as well as cause chain scission and cross-linking, resulting in different behaviors than that of the unaged material. To demonstrate the effect of thermaloxidative aging on the mechanical behavior of elastomers, several experimental and theoretical models have been proposed. In view of the large volume of experimental data available on micro-structural evolution in the course of aging, we propose a physics-based data-driven approach to overcome the shortcomings of both phenomenological and micro-mechanical models. This work presents a novel thermodynamically consistent, multiagent machine-learned model for predicting the constitutive behavior of cross-linked elastomers during environmental aging, such as thermo-oxidative and hydrolytic aging for various states of deformation. Single mechanism degradation changes the polymer matrix over time where it is causing chain scission, reduction of cross-links, and morphology change. To capture the idealized Mullins effect and permanent set due to the effect of single aging mechanisms on nonlinear mechanical responses of elastomers, we propose a data-driven model for simulating inelastic elements in a polymer matrix. By using a sequential order reduction, we were able to reduce the 3D stress-strain tensor mapping problem to a small number of super-constrained 1D mapping problems. To systematically classify such mapping problems into a few categories, an assembly of multiple replicated conditional neural network learning agents (L-agents) is used based on our recent work. Each category is represented by a different type of agent. The effect of deformation history, aging time, and aging temperature is captured by this model. The model is validated using a broad collection of data, ranging from our experimental results to data from the literature. In addition, thermodynamic consistency and frame independence are investigated. The most significant achievements of this model are its precision, simplicity, and prediction of inelasticity under various states of deformation. The model’s accuracy and simplicity make it a good option for commercial and industrial applications. Conveniently, due to the model modular nature, it can be expanded in the future to include viscoelasticity and non-isotropic formation for better precision.

Ghaderi, Aref↗
NASA NTRS1995

Silicon Micromachined Sensor for Broadband Vibration Analysis

The development of a family of silicon based integrated vibration sensors capable of sensing mechanical resonances over a broad range of frequencies with minimal signal processing requirements is presented. Two basic general embodiments of the concept were designed and fabricated. The first design was structured around an array of cantilever beams and fabricated using the ARPA sponsored multi-user MEMS processing system (MUMPS) process at the Microelectronics Center of North Carolina (MCNC). As part of the design process for this first sensor, a comprehensive finite elements analysis of the resonant modes and stress distribution was performed using PATRAN. The dependence of strain distribution and resonant frequency response as a function of Young's modulus in the Poly-Si structural material was studied. Analytical models were also studied. In-house experimental characterization using optical interferometry techniques were performed under controlled low pressure conditions. A second design, intended to operate in a non-resonant mode and capable of broadband frequency response, was proposed and developed around the concept of a cantilever beam integrated with a feedback control loop to produce a null mode vibration sensor. A proprietary process was used to integrat a metal-oxide semiconductor (MOS) sensing device, with actuators and a cantilever beam, as part of a compatible process. Both devices, once incorporated as part of multifunction data acquisition and telemetry systems will constitute a useful system for NASA launch vibration monitoring operations. Satellite and other space structures can benefit from the sensor for mechanical condition monitoring functions.

Gutierrez, Adolfo↗
DOE OSTI2024

Structural basis of DNA recognition of the Campylobacter jejuni CosR regulator

Campylobacter jejuni is a foodborne pathogen commonly found in the intestinal tracts of animals. This pathogen is a leading cause of gastroenteritis in humans. Besides its highly infectious nature, C. jejuni is increasingly resistant to a number of clinically administrated antibiotics. As a consequence, the Centers for Disease Control and Prevention has designated antibiotic-resistant Campylobacter as a serious antibiotic resistance threat in the United States. The C. jejuni CosR regulator is essential to the viability of this bacterium and is responsible for regulating the expression of a number of oxidative stress defense enzymes. Importantly, it also modulates the expression of the CmeABC multidrug efflux system, the most predominant and clinically important system in C. jejuni that mediates resistance to multiple antimicrobials. Here, we report structures of apo-CosR and CosR bound with a 21 bp DNA sequence located at the cmeABC promotor region using both single-particle cryo-electron microscopy and X-ray crystallography. These structures allow us to propose a novel mechanism for CosR regulation that involves a long-distance conformational coupling and rearrangement of the secondary structural elements of the regulator to bind target DNA.

CosR-DNA complex↗
DOE OSTI2021

Metagenomic insights into the taxonomy, function, and dysbiosis of prokaryotic communities in octocorals

Background. In octocorals (Cnidaria Octocorallia), the functional relationship between host health and its symbiotic consortium has yet to be determined. Here, we employed comparative metagenomics to uncover the distinct functional and phylogenetic features of the microbiomes of healthy Eunicella gazella, Eunicella verrucosa, and Leptogorgia sarmentosa tissues, in contrast with the microbiomes found in seawater and sediments. We further explored how the octocoral microbiome shifts to a pathobiome state in E. gazella. Results. Multivariate analyses based on 16S rRNA genes, Clusters of Orthologous Groups of proteins (COGs), Protein families (Pfams), and secondary metabolite-biosynthetic gene clusters annotated from 20 Illumina-sequenced metagenomes each revealed separate clustering of the prokaryotic communities of healthy tissue samples of the three octocoral species from those of necrotic E. gazella tissue and surrounding environments. While the healthy octocoral microbiome was distinguished by so-far uncultivated Endozoicomonadaceae, Oceanospirillales, and Alteromonadales phylotypes in all host species, a pronounced increase of Flavobacteriaceae and Alphaproteobacteria, originating from seawater, was observed in necrotic E. gazella tissue. Increased abundances of eukaryotic-like proteins, exonucleases, restriction endonucleases, CRISPR/Cas proteins, and genes encoding for heat-shock proteins, inorganic ion transport, and iron storage distinguished the prokaryotic communities of healthy octocoral tissue regardless of the host species. An increase of arginase and nitric oxide reductase genes, observed in necrotic E. gazella tissues, suggests the existence of a mechanism for suppression of nitrite oxide production by which octocoral pathogens may overcome the host’s immune system. Conclusions. This is the first study to employ primer-less, shotgun metagenome sequencing to unveil the taxonomic, functional, and secondary metabolism features of prokaryotic communities in octocorals. Our analyses reveal that the octocoral microbiome is distinct from those of the environmental surroundings, is host genus (but not species) specific, and undergoes large, complex structural changes in the transition to the dysbiotic state. Host-symbiont recognition, abiotic-stress response, micronutrient acquisition, and an antiviral defense arsenal comprising multiple restriction endonucleases, CRISPR/Cas systems, and phage lysogenization regulators are signatures of prokaryotic communities in octocorals. We argue that these features collectively contribute to the stabilization of symbiosis in the octocoral holobiont and constitute beneficial traits that can guide future studies on coral reef conservation and microbiome therapy.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2011

Low Fluid Shear Culture of Staphylococcus Aureus Represses hfq Expression and Induces an Attachment-Independent Biofilm Phenotype

Background: The opportunistic pathogen, Staphylococcus aureus, experiences fluctuations in fluid shear during infection and colonization of a human host. Colonization frequently occurs at mucus membrane sites such as in the gastrointestinal tract where the bacterium may experience low levels of fluid shear. The response of S. aureus to low fluid shear remains unclear. Methods: S. aureus was cultured to stationary phase using Rotating-Wall Vessel (RWV) bioreactors which produce a physiologically relevant low fluid shear environment. The bacterial aggregates that developed in the RWV were evaluated by electron microscopy as well as for antibiotic resistance and other virulence-associated stressors. Genetic expression profiles for the low-shear cultured S. aureus were determined by microarray analysis and quantitative real-time PCR. Results: Planktonic S. aureus cultures in the low-shear environment formed aggregates completely encased in high amounts of extracellular polymeric substances. In addition, these aggregates demonstrated increased antibiotic resistance indicating attachment-independent biofilm formation. Carotenoid production in the low-shear cultured S. aureus was significantly decreased, and these cultures displayed an increased susceptibility to oxidative stress and killing by whole blood. The hfq gene, associated with low-shear growth in Gram negative organisms, was also found to be down-regulated in S. aureus. Conclusions: Collectively, this data suggests that S. aureus decreases virulence characteristics in favor of a biofilm-dwelling colonization phenotype in response to a low fluid shear environment. Furthermore, the identification of an Hfq response to low-shear culture in S. aureus, in addition to the previously reported responses in Gram negative organisms, strongly suggests an evolutionarily conserved response to mechanical stimuli among structurally diverse prokaryotes.

Ott, C. Mark↗
NASA NTRS1996

RAINBOWS and CERAMBOWS: The Technologies of Pre-Stressed Piezo Actuators

Amplified mechanical displacement effects, similar to those observed in the recently reported Rainbow actuators, have also been found to exist in prestressed ceramic/metal composite structures coined as CERAMBOW's - an acronym for CERamic And Metal Biased Oxide Wafer. Mimicking the Rainbows in many ways, the intentionally created internal compressive and tensile stresses within the Cerambows are used to amplify their displacement properties via the combined effects of piezoelectric d31 strain and domain reorientation. They are fabricated from ferroelectric, piezoelectric or electrostrictive materials and metal substrates of significantly different thermal expansions which are largely responsible for the creation of the stress. Typical ceramics used in Cerambows are PZT, PLZT, PBZT, PSZT and PMN and some typical metal substrates are Al, Ag, Ni, brass, steel and Be/Cu foil. Shapes can vary from round disks to square plates and rectangular bars. Formed at an elevated temperature of approximately 250 C, the stresses on cooling to room temperature are generally sufficient to produce displacements as large as 0.125mm (5 mils) when activated unipolar and 0.25mm (10 mils) when operated bipolar at 450 volts in a dome mode. Comparing equal structures of a Cerambow with a Rainbow, the Cerambow was found to achieve approximately 70% of the displacement that would normally be obtained with a Rainbow. Although this difference in displacement is sufficient to prefer a Rainbow for many applications, there are some advantages for the Cerambow. Among these are (1) the processing temperatures are lower, (2) high lead-containing ceramics are not required and (3) in some instances the metal substrate is more convenient to interface with other elements of a device. However, the disadvantages include (1) lower displacement in the dome mode of operation, (2) the higher displacement saddle mode has not yet been demonstrated with a Cerambow and (3) the ceramic/metal bond interface is a possible failure area when operated for extended periods of time. The applications for Cerambows are considered to be similar to Rainbows, i.e., actuators, pumps, deflectors, vibrators, speakers, hydrophones, hydroprojectors, switches, etc.

Haertling, Gene H.↗