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NASA NTRS2001

Ecological physiology of Synechococcus sp. strain SH-94-5, a naturally occurring cyanobacterium deficient in nitrate assimilation

Synechococcus sp. strain SH-94-5 is a nitrate assimilation-deficient cyanobacterium which was isolated from an ammonium-replete hot spring in central Oregon. While this clone could grow on ammonium and some forms of organic nitrogen as sole nitrogen sources, it could not grow on either nitrate or nitrite, even under conditions favoring passive diffusion. It was determined that this clone does not express functional nitrate reductase or nitrite reductase and that the lack of activity of either enzyme is not due to inactivation of the cyanobacterial nitrogen control protein NtcA. A few other naturally occurring cyanobacterial strains are also nitrate assimilation deficient, and phylogenetic analyses indicated that the ability to utilize nitrate has been independently lost at least four times during the evolutionary history of the cyanobacteria. This phenotype is associated with the presence of environmental ammonium, a negative regulator of nitrate assimilation gene expression, which may indicate that natural selection to maintain functional copies of nitrate assimilation genes has been relaxed in these habitats. These results suggest how the evolutionary fates of conditionally expressed genes might differ between environments and thereby effect ecological divergence and biogeographical structure in the microbial world.

Nitrates/metabolism↗

NASA NTRSDate not supplied

Transcriptomic Changes in Peripheral Blood Mononuclear Cells of International Space Station Crewmembers

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the ground control subjects of all of the time points combined as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of SMAD7 and CDKN1A at MF and LF. Some of the genes such as SERPINE1 and VEGFA were downregulated at MF and LF, but upregulated at R0, while others such as NKG7 were down regulated at all of the 3 time points. Pathway analysis of these differentially expressed genes indicated that the NF-κB pathway was chronically activated in space. Analysis of the consequent diseases suggested potential associations with not only immune dysfunction, but also other health risks including osteoarthritis, cardiac hypertrophy and neuroinflammation.

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Gene expression changes in peripheral blood mononuclear cells of ISS crewmembers suggest impacts of spaceflight on cell death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, our data suggests that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight.

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Gene Expression Changes in Peripheral Blood Mononuclear Cells of ISS Crewmembers Suggest Impacts of Spaceflight on Cell Death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, we hypothesize that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Transcriptomic Changes in Peripheral Blood Mononuclear Cells of International Space Station Crewmembers

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) Blood was drawn at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 36 hours (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the ground control subjects of all time points combined as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of SMAD7 and CDKN1A at MF and LF. Some of the genes such as SERPINE1 and VEGFA were downregulated at MF and LF, but upregulated at R0, while others such as NKG7 were down regulated at all 3 time points. Pathway analysis of these differentially expressed genes indicated that the NF-κB pathway was chronically activated in space. Analysis of the consequent diseases suggested potential associations with not only immune dysfunction, but also other health risks including osteoarthritis, cardiac hypertrophy and neuroinflammation.

Maria Moreno-Villanueva↗

NASA NTRSDate not supplied

Transcriptomic Changes in ISS Crewmembers Suggest Decreased Metabolic Activity in Peripheral Blood Mononuclear Cells

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) Blood was drawn at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 36 hours (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the ground control subjects of all time points combined as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, Pathway analysis of these differentially expressed genes indicated that several of the pathways related to metabolism, including LXR/RXR, NAD signaling and fatty acid betta-oxidation, were downregulated at MF and LF. We suggest that the decreased metabolic activity in space may contribute to the immune dysfunction and delayed cell cycle progression as observed in the astronauts.

Maria Moreno-Villanueva↗

NASA NTRS1995

PCR Based Microbial Monitor for Analysis of Recycled Water Aboard the ISSA: Issues and Prospects

The monitoring of spacecraft life support systems for the presence of health threatening microorganisms is paramount for crew well being and successful completion of missions. Development of technology to monitor spacecraft recycled water based on detection and identification of the genetic material of contaminating microorganisms and viruses would be a substantial improvement over current NASA plans to monitor recycled water samples that call for the use of conventional microbiology techniques which are slow, insensitive, and labor intensive. The union of the molecular biology techniques of DNA probe hybridization and polymerase chain reaction (PCR) offers a powerful method for the detection, identification, and quantification of microorganisms and viruses. This technology is theoretically capable of assaying samples in as little as two hours with specificity and sensitivity unmatched by any other method. A major advance in probe-hybridization/PCR has come about in a technology called TaqMan(TM), which was invented by Perkin Elmer. Instrumentation using TaqMan concepts is evolving towards devices that could meet NASA's needs of size, low power use, and simplicity of operation. The chemistry and molecular biology needed to utilize these probe-hybridization/PCR instruments must evolve in parallel with the hardware. The following issues of chemistry and biology must be addressed in developing a monitor: Early in the development of a PCR-based microbial monitor it will be necessary to decide how many and which organisms does the system need the capacity to detect. We propose a set of 17 different tests that would detect groups of bacteria and fungus, as well as specific eukaryotic parasites and viruses; In order to use the great sensitivity of PCR it will be necessary to concentrate water samples using filtration. If a lower limit of detection of 1 microorganism per 100 ml is required then the microbes in a 100 ml sample must be concentrated into a volume that can be added to a PCR assay; There are not likely to be contaminants in ISSA recycled water that would inhibit PCR resulting in false-negative results; The TaqMan PCR product detection system is the most promising method for developing a rapid, highly automated gene-based microbial monitoring system. The method is inherently quantitative. NASA and other government agencies have invested in other technologies that, although potentially could lead to revolutionary advances, are not likely to mature in the next 5 years into working systems; PCR-based methods cannot distinguish between DNA or RNA of a viable microorganism and that of a non-viable organism. This may or may not be an important issue with reclaimed water on the ISSA. The recycling system probably damages the capacity of the genetic material of any bacteria or viruses killed during processing to serve as a template in a PCR desinged to amplify a large segment of DNA (less than 650 base pairs). If necessary, vital dye staining could be used in addition to PCR, to enumerate the viable cells in a water sample; The quality control methods have been developed to insure that PCR's are working properly, and that reactions are not contaminated with PCR carryover products which could lead to the generation of false-positive results; and The sequences of the small rRNA subunit gene for a large number of microorganisms are known, and they consititue the best database for rational development of the oligonucleotide reagents that give PCR its great specificity. From those gene sequences, sets of oligonucleotide primers for PCR and Taqman detection that could be used in a NASA microbial monitor were constructed using computer based methods. In addition to space utilization, a microbial monitior will have tremendous terrestrial applications. Analysis of patient samples for microbial pathogens, testing industrial effluent for biofouling bacteria, and detection biological warfare agents on the battlefield are but a few of the diverse potential uses for this technology. Once fully developed, gene-based microbial monitors will become the fundamental tool in every lab that tests for microbial contaminants, and serve as a powerful weapon in mankind's war with the germ world.

Cassell, Gail H.↗

DOE OSTI2025

A Comprehensive Study of the Impact of Inverter-Based Resource (IBR) Modeling and Control on Protection Relay Elements

Inverter-based resources (IBRs) exhibit fault responses that differ significantly from those of synchronous generators, which can challenge the reliable operation of many commonly used power system protection elements. The fault response of IBRs is primarily influenced by their control algorithms and configurations, but the impact of these controls on protection relays is not yet fully understood. This presentation provides a comprehensive study of how IBR modeling and controls affect transmission line protection. Key modeling and control aspects include the DC source, inverter model, power level control, current control, and current limiting. The study reveals that certain aspects - such as the type of DC source (battery, PV, or hybrid), inverter model (average vs. switching), and power level control methods (PQ dispatch vs. Vdc-Vac control for grid-following IBRs, and droop vs. VSM for grid-forming IBRs) - do not significantly affect relay response. However, faster control loops, such as current control and current limiting, do influence the relay behavior. Additionally, the study explores the effects of other factors, including momentary cessation, operating points, fast/slow current responses, and grid strength on relay performance. Finally, the study offers recommendations for both IBR and protection engineers to improve IBR fault response and enhance the reliability of protection systems.

14 SOLAR ENERGY↗

NASA NTRS1999

Microgravity Experiments to Evaluate Electrostatic Forces in Controlling Cohesion and Adhesion of Granular Materials

The bulk behavior of dispersed, fluidized, or undispersed stationary granular systems cannot be fully understood in terms of adhesive/cohesive properties without understanding the role of electrostatic forces acting at the level of the grains themselves. When grains adhere to a surface, or come in contact with one another in a stationary bulk mass, it is difficult to measure the forces acting on the grains, and the forces themselves that induced the cohesion and adhesion are changed. Even if a single gain were to be scrutinized in the laboratory, it might be difficult, perhaps impossible, to define the distribution and character of surface charging and the three- dimensional relationship that charges (electrons, holes) have to one another. The hypothesis that we propose to test in microgravity (for dielectric materials) is that adhesion and cohesion of granular matter are mediated primarily by dipole forces that do not require the presence of a net charge; in fact, nominally electrically neutral materials should express adhesive and cohesive behavior when the neutrality results from a balance of positive and negative charge carriers. Moreover, the use of net charge alone as a measure of the electrical nature of grain-to-grain relationships within a granular mass may be misleading. We believe that the dipole forces arise from the presence of randomly-distributed positive and negative fixed charge carriers on grains that give rise to a resultant dipole moment. These dipole forces have long-range attraction. Random charges are created whenever there is triboelectrical activity of a granular mass, that is, whenever the grains experience contact/separation sequences or friction. Electrostatic forces are generally under-estimated for their role in causing agglomeration of dispersed grains in particulate clouds, or their role in affecting the internal frictional relationships in packed granular masses. We believe that electrostatic, in particular dipole-mediated processes, are pervasive and probably affect, at some level, everything from astrophysical-scale granular systems such as interstellar nebulae, protoplanetary dust and debris disks, planetary-scale systems such as debris palls from meteorite impact, volcanic eruptions, and aeolian dust storms, all the way to industrial-scale systems in mining, powder and grain processing, pharmaceuticals, and smoke-stack technologies. NASA must concern itself with the electrostatic behavior of dust and sand on Mars because of its potentially critical importance to human exploration. The motion and adhesion of martian surface materials will affect the design and performance of spacesuits, habitats, processing plants, solar panels, and any externally exposed equipment such as surface rovers or communication and weather stations. Additionally, the adhesion of dust and sand could greatly enhance contact with the potentially toxic components of the martian soil.

Marshall, J.↗

NASA NTRS1999

Microgravity Experiments to Evaluate Electrostatic Forces in Controlling Cohesion and Adhesion of Granular Materials

Marshall, J.↗

DOE OSTI2026

Evaluation of a Reduced-Order Model for IBR Fault Response Representation via OEM Blackbox Models: Preprint

Driven by the need to capture the electromagnetic transients of transmission lines, inverter switching behavior, and detailed control systems, electromagnetic transient (EMT) studies have become increasingly important in industry, such as IBR interconnection study and fault study. However, original equipment manufacturer (OEM) inverter models typically include extensive parameters and proprietary settings that are unavailable to protection engineers. This paper introduces a data-driven, reduced-order model (ROM) developed as a PSCAD library component for use in EMT-based fault studies. The ROM replicates key OEM model behaviors without requiring detailed knowledge of control design or parameterization. The accompanying Python automation scripts streamline data generation, parameter fitting, and validation. The ROM's performance is demonstrated through comparison with both IEEE 2800-compliant and non-compliant OEM models in a real-world power system. Relay responses show nearly identical results, while simulation runtime is reduced by an average of 32.8\%, highlighting the ROM's practicality for protection engineers.

14 SOLAR ENERGY↗

NASA NTRS1998

Phylogenetic mapping of bacterial morphology

The availability of a meaningful molecular phylogeny for bacteria provides a context for examining the historical significance of various developments in bacterial evolution. Herein, the classical morphological descriptions of selected members of the domain Bacteria are mapped upon the genealogical ancestry deduced from comparison of small-subunit rRNA sequences. For the species examined in this study, a distinct pattern emerges which indicates that the coccus shape has arisen and accumulated independently multiple times in separate lineages and typically survived as a persistent end-state morphology. At least two other morphologies persist but have evolved only once. This study demonstrates that although bacterial morphology is not useful in defining bacterial phylogeny, it is remarkably consistent with that phylogeny once it is known. An examination of the experimental evidence available for morphogenesis as well as microbial fossil evidence corroborates these findings. It is proposed that the accumulation of persistent morphologies is a result of the biophysical properties of peptidoglycan and their genetic control, and that an evolved body-plan strategy based on peptidoglycan may have been a fate-sealing step in the evolution of Bacteria. More generally, this study illustrates that significant evolutionary insights can be obtained by examining biological and biochemical data in the context of a reliable phylogenetic structure.

NASA Discipline Exobiology↗

DOE OSTI2021

A Deep Learning Modeling Framework to Capture Mixing Patterns in Reactive-Transport Systems

Prediction and control of chemical mixing are vital for many scientific areas such as subsurface reactive transport, climate modeling, combustion, epidemiology, and pharmacology. Due to the complex nature of mixing in heterogeneous and anisotropic media, the mathematical models related to this phenomenon are not analytically tractable. Numerical simulations often provide a viable route to predict chemical mixing accurately. However, contemporary modeling approaches for mixing cannot utilize available spatial-temporal data to improve the accuracy of the future prediction and can be compute-intensive, especially when the spatial domain is large and for long-term temporal predictions. To address this knowledge gap, in this work we will present in this paper a deep learning (DL) modeling framework applied to predict the progress of chemical mixing under fast bimolecular reactions. This framework uses convolutional neural networks (CNN) for capturing spatial patterns and long short-term memory (LSTM) networks for forecasting temporal variations in mixing. By careful design of the framework—placement of non-negative constraint on the weights of the CNN and the selection of activation function, the framework ensures non-negativity of the chemical species at all spatial points and for all times. Our DL-based framework is fast, accurate, and requires minimal data for training. The time needed to obtain a forecast using the model is a fraction (≈ O(-6)) of the time needed to obtain the result using a high-fidelity simulation. To achieve an error of 10% (measured using the infinity norm) for capturing local-scale mixing features such as interfacial mixing, only 24% to 32% of the sequence data for model training is required. To achieve the same level of accuracy for capturing global-scale mixing features, the sequence data required for model training is 64% to 70% of the total spatial-temporal data. Hence, the proposed approach—a fast and accurate way to forecast long-time spatial-temporal mixing patterns in heterogeneous and anisotropic media—will be a valuable tool for modeling reactive-transport in a wide range of applications.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2025

Physiological roles of an Acinetobacter -specific σ factor

ABSTRACT The Gram-negative pathogen Acinetobacter baumannii is considered an “urgent threat” to human health due to its propensity to become antibiotic resistant. Understanding the distinct regulatory paradigms used by A. baumannii to mitigate cellular stresses may uncover new therapeutic targets. Many γ-proteobacteria use the extracytoplasmic function (ECF) σ factor, RpoE, to invoke envelope homeostasis networks in response to stress. Acinetobacter species contain the poorly characterized ECF “SigAb”; however, it is unclear if SigAb has the same physiological role as RpoE. Here, we show that SigAb is a metal stress-responsive ECF that appears unique to Acinetobacter species and distinct from RpoE-like ECFs. We combine promoter mutagenesis, motif scanning, and chromatin immunoprecipitation-sequencing (ChIP-seq) to define the direct SigAb regulon, which consists of genes encoding SigAb itself, the stringent response mediator, RelA, and the uncharacterized small RNA, “SabS.” However, RNA-seq of strains overexpressing SigAb revealed a large, indirect regulon containing hundreds of genes. Metal resistance genes are key elements of the indirect regulon, as CRISPRi knockdown of sigAb or sabS resulted in increased copper sensitivity and excess copper-induced SigAb-dependent transcription. Furthermore, we found that two uncharacterized genes in the sigAb operon, “ aabA ” and “ aabB ,” have anti-SigAb activity. Finally, employing a targeted Tn-seq approach that uses CRISPR-associated transposons, we show that sigAb , aabA , and aabB are important for fitness even during optimal growth conditions. Our work reveals new physiological roles for SigAb and SabS, provides a novel approach for assessing gene fitness, and highlights the distinct regulatory architecture of A. baumannii . IMPORTANCE Acinetobacter baumannii is a hospital-acquired pathogen, and many strains are resistant to multiple antibiotics. Understanding how A. baumannii senses and responds to stress may uncover novel routes to treat infections. Here, we examine how the Acinetobacter -specific transcription factor, SigAb, mitigates stress. We find that SigAb directly regulates only a small number of genes, but indirectly controls hundreds of genes that have substantial impacts on cell physiology. We show that SigAb is required for maximal growth, even during optimal conditions, and is acutely required during growth in the presence of elevated copper. Given that copper toxicity plays roles in pathogenesis and on copper-containing surfaces in hospitals, we speculate that SigAb function may be important in clinically relevant contexts.

Bacon, Emily E. (ORCID:0000000180907689)↗

NASA NTRSDate not supplied

Intracranial Effects of Intermittent Lower Body Negative Pressure with Head Down Tilt Bed Rest: Comparison to Upright Posture

INTRODUCTION Spaceflight-associated neuro-ocular syndrome (SANS) affects a majority of astronauts during long-duration spaceflight. SANS is hypothesized to result from an unrelenting headward fluid shift that occurs in the microgravity environment. Altered intracranial structure and physiology documented in spaceflight and head-down tilt (HDT) experiments(1, 2) are also theorized to be related to chronic headward fluid shift and thereby can provide an independent quantitative assessment related to this mechanism. As a potential countermeasure, lower body negative pressure (LBNP) applied in the supine posture has shown efficacy in reducing headward fluid shift(3). However, it remains unknown if intermittent LBNP simulating daily upright posture fluid redistribution can mitigate SANS and intracranial changes associated with long-duration spaceflight. The goal of this study was to quantify the effects of daily application of LBNP or daily exposure to the upright posture on intracranial structure and physiology during long-term HDT in order to evaluate the potential efficacy of LBNP as a countermeasure to SANS. METHODS 22 healthy volunteers (11 men; 11 women; mean age = 35 years (SD=9.2)(age range = 24 to 52 years); mean BMI = 24.0 kg/m2 (SD=2.8)) completed an MRI study performed at the German Aerospace Facility in Cologne, Germany. Strict six-degree head-down tilt (HDT) bedrest was used as a spaceflight analog to induce a continuous headward fluid shift for 30 days. The subjects were divided equally into two groups of interventions: 1) LBNP for 3-hour sessions twice daily and 2) seated position for 3-hour sessions twice daily. Interventions were divided into morning and afternoon sessions for both groups. The LBNP intervention was maintained at 25 mmHg  2 mmHg. Pulse-gated MRI phase-contrast flow imaging was used to quantify cerebral artery stroke volume (CASV) and peak-to-peak cerebral spinal fluid (CSF) velocity (CSFVp-p) within the cerebral aqueduct. A 3D T1-MPRAGE sequence was used to quantify volumetric changes of the brain and intracranial CSF spaces using MRI Cloud software. MRI acquisitions were obtained at baseline (BDC, supine posture), 15 days into HDT (HDT15), 29 days into HDT (HDT29), and 12 days after recovery (R12, supine posture). The data were analyzed by a mixed model, which included intervention, time (four nominal levels BDC, HDT15, HDT29, R12), and intervention-time interaction as the fixed effects and included subject as a random effect. RESULTS Compared to BDC there was no statistically significant difference in CASV and CSFVp-p during HDT except for CASV at HDT29 (seated group) where there was a 1.7 mL (12%) decrease (P<0.01). Compared to BDC there was a statistically significant increase in intracranial volume (ICV; ICV = white matter + gray matter + CSF) for both interventions at HDT15 (Δ13 mL, 0.9 % (LBNP group); Δ15 mL, 1.0%, (seated group)) and HDT29 (Δ19 mL, 1.2%, (LBNP group); Δ23 mL, 1.5%) (seated group)) (All Ps<.001). Compared to baseline, lateral ventricular volume increased at HDT15 (Δ0.9 mL, 5.5%) and HDT29 (Δ1.8 mL, 10%)) for LBNP only (P=.001 for each). During HDT, white matter volume remained stable compared to baseline for both interventions. There were no significant intervention effects in the overall response to HDT (All Ps >.2). CONCLUSION LBNP had a similar response to the seated posture during 29 days of HDT. Although there was an increase in ICV and lateral ventricular volume with HDT there was no change in intracranial physiological parameters with LBNP suggesting an overall diminished response to the long-term effects of HDT. The lack of any significant increase in white matter volume during HDT with LBNP suggests maintenance of cerebral interstitial fluid transport. Final conclusions are pending the data collection for the control group (no intervention) which will be completed in 2023.

Larry A Kramer↗

DOE OSTI2025

Bayesian estimation of HIV acquisition dates for prevention trials

Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, “true DDA” was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2–7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days).

59 BASIC BIOLOGICAL SCIENCES↗