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At least 325 records · Page 18

Publications of the exobiology program for 1990: A special bibliography

The Exobiology Program is an integrated program designed to investigate and understand those processes related to the origin, evolution, and distribution of life in the universe. The Exobiology Program is broad in scope, covering the following subject areas: cosmic evolution of biogenic compounds; prebiotic evolution; early evolution of life; evolution of advanced life; solar system exploration; search for extraterrestrial intelligence; planetary protection; and advanced programs in biological systems research. A listing of the 1990 publications resulting from research supported by the Exobiology Program is presented.

Source record↗

Modeling the Normal and Neoplastic Cell Cycle with 'Realistic Boolean Genetic Networks': Their Application for Understanding Carcinogenesis and Assessing Therapeutic Strategies

In this paper we show how Boolean genetic networks could be used to address complex problems in cancer biology. First, we describe a general strategy to generate Boolean genetic networks that incorporate all relevant biochemical and physiological parameters and cover all of their regulatory interactions in a deterministic manner. Second, we introduce 'realistic Boolean genetic networks' that produce time series measurements very similar to those detected in actual biological systems. Third, we outline a series of essential questions related to cancer biology and cancer therapy that could be addressed by the use of 'realistic Boolean genetic network' modeling.

Szallasi, Zoltan↗

Beyond the Prototype: The Design Evolution of a Deployed AI System

Our previous experiences with deployed intelligent control agents for NASA advanced life support systems (Schreckenghost et al., 2002) inspired us to develop the Distributed Collaboration and Interaction (DCI) system to help humans and mostly-autonomous software agents work together. We discovered many unaddressed needs for human interaction with control agents that operate continuously over months to years to monitor and perform process control for regenerative life support systems. These systems recover usable water or air from the waste products created by biological systems over time. Through the DCI project, we have addressed the needs for interaction between humans and autonomous control systems. This paper describes the software engineering aspects of our experiences, first, in designing and developing a prototype of the DCI system, and later, in adjusting the implementation to make the leap from initial prototype to a system ready to be applied under varying circumstances to meet different needs. The details in the paper focus primarily on the second stage of development. The DCI system is currently deployed, operating 24/7, to assist humans to interact with an advanced Water Recovery System (WRS). In addition, we have demonstrated an application of DCI to support ground personnel in mission support roles.

Martin, C.↗

Beyond the Prototype: The Design Evolution of a Deployed AI System

Our previous experiences with deployed intelligent control agents for NASA advanced life support systems (Schreckenghost et al., 2002) inspired us to develop the Distributed Collaboration and Interaction (DCI) system to help humans and mostly-autonomous software agents work together. We discovered many unaddressed needs for human interaction with control agents that operate continuously over months to years to monitor and perform process control for regenerative life support systems. These systems recover usable water or air from the waste products created by biological systems over time. Through the DCI project, we have addressed the needs for interaction between humans and autonomous control systems. This paper describes the software engineering aspects of our experiences, first, in designing and developing a prototype of the DCI system, and later, in adjusting the implementation to make the leap from initial prototype to a system ready to be applied under varying circumstances to meet different needs. The details in the paper focus primarily on the second stage of development. The DCI system is currently deployed, operating 24/7, to assist humans to interact with an advanced Water Recovery System (WRS). In addition, we have demonstrated an application of DCI to support ground personnel in mission support roles.

Martin, Cheryl↗

Computation-guided optimization of split protein systems

Splitting bioactive proteins into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biological systems. However, split proteins often exhibit a high propensity to reconstitute, even without the conditional trigger, limiting their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific or often ineffective. Here, we report a computational design strategy grounded in fundamental protein biophysics to guide experimental evaluation of a sparse set of mutants to identify an optimal functional window. We hypothesized that testing a limited set of mutants would direct subsequent mutagenesis efforts by predicting desirable mutant combinations from a vast mutational landscape. This strategy varies the degree of interfacial destabilization while preserving stability and catalytic activity. We validate our method by solving two distinct split protein design challenges, generating both design and mechanistic insights. Furthermore, this new technology will streamline the generation and use of split protein systems for diverse applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

New molecular components of high and low affinity iron import systems in Drosophila

The high abundance and molecular versatility of iron have led to its universal presence in biological systems, yet its absorption is exceptionally challenging. Animals and yeasts use divalent metal transporters to import iron, but yeasts also employ the multicopper oxidase Fet3p for high-affinity iron uptake when iron-starved. Using long-term iron depletion in Drosophila, we identified four components involved in iron absorption: Multicopper oxidase-4 (Mco4), a Fet3p ortholog, is essential for surviving iron starvation, whereas the cytochrome b561 enzymes Fire (Ferric Iron Reductase) and Fire-like, as well as cytochrome b5 protein Firewood, are required for iron absorption under normal conditions. This study reports the presence of a high-affinity iron uptake system in an animal, a cytochrome b5 electron donor for ferric iron reduction, and intestinal ferric reductases, and provides a valuable resource for further exploration of genes involved in iron homeostasis, transport, and absorption.

Iron↗

Support system considerations for STS biological investigations

Equipment required for Space Transportation System biological experiments is considered, and environmental factors and operational constraints affecting the performance of experiments are examined. Specimen housing is discussed, problems associated with telemetry procedures are characterized, and attention is directed to the problems of handling hazardous fixatives, radioisotopes, and chemicals.

Bowman, G. H.↗

Using the NASA GeneLab Data System to Study the Metagenomes of Spaceships and Their Occupants

With humans pushing to live further off Earth for longer periods of time, it is increasingly important to understand the changes that occur in biological systems during spaceflight whether these be astronauts, their microbial commensals, or their plant-based life support systems. In a three-part presentation, we discuss GeneLab and recent discoveries regarding the microbiota of spacecrafts and space-flown animals. Part 1: GeneLab: Open Science for Life in Space, Jonathan Galazka, NASA Ames Research Center To accelerate the pace of discovery from precious spaceflight biological experiments, NASA as develop the GeneLab data system (genelab.nasa.gov), which allows unfettered access to omics data from spaceflight and spaceflight relevant experiments. GeneLab houses metagenomic datasets from spacecraft and relevant spacecraft models. Users can download this data and associated metadata to make new discoveries about how microbial communities may change and adapt to spaceflight.

Galazka, Jonathan M.↗

A state-of-the-art review of experimental and computational studies of granular materials: Properties, advances, challenges, and future directions

Modeling of heterogeneous materials and media is a problem of fundamental importance to a wide class of phenomena and systems, ranging from condensed matter physics, soft materials, and composite media to porous media, biological systems, geosystems, ceramic engineering, pharmaceutical science and even in space discoveries. Among the most important materials are granular systems, which have received intense interest from the engineering, physics, and mathematics communities. In this review paper, the recent developments and new advances in experimental, and computational methods on a variety of scales and physics that extend understanding to a wide range of materials and phenomena are reviewed. Experimental advances include computed neutron and nanometer-scale tomography, magnetic resonance imaging, refractive index matching, digital image correlation, acoustic emission analysis, and the most recent 4D techniques. Furthermore, a tremendous shift has occurred from the continuum scale to micro-scale and developing multiscale approaches. As such, various computational methods, including, constitutive modeling, discrete modeling, and multiscale approaches, have been developed. In conclusion, aside from all these evolutions, more complicated modeling called coupled, or multiphysics, systems representing a simultaneous presence of heat, fluid, chemical variation, and mechanical effect are also explored.

36 MATERIALS SCIENCE↗

2025 Workshop on Envisioning Frontiers in AI and Computing for Biological Research: Position Papers

This workshop aims to identify key research directions for transforming biology using artificial intelligence (AI), machine learning (ML) and computational methods to facilitate the discovery of new behaviors, mechanisms, and designs of biological processes relevant to DOE missions, underpinning a broader U.S. bioeconomy. By developing novel AI/ML technologies to analyze and interpret complex biological data, researchers can organize and simulate biological processes at various scales as well as advance predictive understanding and manipulation of biological systems. This integration of computation, experimentation, and next-generation experimental technologies can lead to discoveries in new biological behaviors and mechanisms relevant to DOE missions. The focus is on how advanced computational and mathematical methods can impact this mission by exploring digital twins, foundation models, automated laboratory experiments, modeling of complex living systems, and data-driven approaches for the biodesign of plants and microbial systems. While data management is important, it is not the primary focus of this workshop, which will assess the current state, trends, and AI/ML challenges at the interface between biology and computational science to identify opportunities for high-impact research at their intersection. The goal is to define research needs and opportunities that align with biological sciences, computational sciences, and applied mathematics research.

59 BASIC BIOLOGICAL SCIENCES↗

The Systems of Radiological Protection for Ionizing and Non-Ionizing Radiation

This paper summarizes the presentations and panel discussion held at Plenary Session 1 of the 16th IRPA International Congress/69th Health Physics Society Annual Meeting, in Orlando, FL, in July 2024. Plenary Session 1 discussed the basics of the systems of radiological protection (RP) for ionizing radiation (IR) and non-ionizing radiation (NIR) and included five presentations and a panel discussion. Rodney Croft, Chair of the International Commission on Non-Ionizing Radiation Protection (ICNIRP), delivered the first presentation. Croft introduced the System of RP for NIR and provided an overview of ICNIRP’s coverage and current areas of work. Werner Rühm, Chair of the International Commission on Radiological Protection (ICRP), delivered the second presentation. He gave an overview of the System of RP for IR and covered the key principles of justification, optimization, and dose limitation, including the current plans of ICRP toward the envisaged revision of the System of RP. The third speaker, Sigurður Magnús Magnússon, from the International Radiation Protection Association (IRPA), provided the perspective of the RP professionals on the development of the Systems of RP for IR and NIR. Emilie van Deventer, from the World Health Organization (WHO), presented WHO’s views of both Systems of RP and discussed the relevant current activities of WHO with regard to IR and NIR. Kathryn Higley, President of the National Council on Radiation Protection and Measurements (NCRP), delivered the final presentation. Higley outlined the history of NCRP, the differences between ICRP and NCRP, and discussed the role of the NCRP in the System of RP, including NCRP’s role to analyze mechanisms of interaction of NIR with biological systems, including humans. The session concluded with a fruitful panel discussion, where the audience had the opportunity to ask the five invited speakers questions.

61 RADIATION PROTECTION AND DOSIMETRY↗

NASA's Plans for Developing Life Support and Environmental Monitoring and Control Systems

Life Support and Monitoring have recently been reworked in response to the Vision for Space Exploration. The Exploration Life Support (ELS) Project has replaced the former Advanced Life Support Element of the Human Systems Research and Technology Office. Major differences between the two efforts include: the separation of thermal systems into a new stand alone thermal project, deferral of all work in the plant biological systems, relocation of food systems to another organization, an addition of a new project called habitation systems, and overall reduction in the number of technology options due to lower funding. The Advanced Environmental Monitoring and Control (AEMC) Element is retaining its name but changing its focus. The work planned in the ELS and AEMC projects is organized around the three major phases of the Exploration Program. The first phase is the Crew Exploration Vehicle (CEV). The ELS and AEMC projects will develop hardware for this short duration orbital and trans-lunar vehicle. The second phase is sortie landings on the moon. Life support hardware for lunar surface access vehicles including upgrades of the CEV equipment and technologies which could not be pursued in the first phase due to limited time and budget will be developed. Monitoring needs will address lunar dust issues, not applicable to orbital needs. The ELS and AEMC equipment is of short duration, but has different environmental considerations. The third phase will be a longer duration lunar outpost. This will consist of a new set of hardware developments better suited for long duration life support and associated monitoring needs on the lunar surface. The presentation will show the planned activities and technologies that are expected to be developed by the ELS and AEMC projects for these program phases.

Lawson, B. Michael↗

In Vitro and in Vivo Analyses of the Effects of Source, Length, and Charge on the Cytotoxicity and Immunocompatibility of Cellulose Nanocrystals

Cellulose nanocrystals (CNCs) are an emergent, sustainable nanomaterial which are bio-sourced, abundant, and biodegradable. On account of their high aspect ratio, low density, and mechanical rigidity, they have been employed in numerous areas of biomedical research including as reinforcing materials for bone or tissue scaffolds or as carriers in drug delivery systems. Given the promise of these materials for such use, characterizing and understanding their interactions with biological systems is an important step to prevent toxicity or inflammation. Reported herein are studies aimed at exploring the in-vitro and in-vivo effects that source, length, and charge of the CNCs have on cytotoxicity and immune response. In this study, CNCs from four different biosources (cotton, wood, Miscanthus x. Giganteus, and sea tunicate) were prepared and functionalized with positive or negative charges to obtain a small library of CNCs with a range of dimensions and surface charge. A method to remove endotoxic or other impurities on the CNC surface leftover from the isolation process was developed, and the biocompatibility of the CNCs was subsequently assayed in-vitro and in-vivo. After subcutaneous injection, it was found that unfunctionalized (uncharged) CNCs form aggregates at the site of injection, inducing splenomegaly and neutrophil infiltration, while charged CNCs having surface carboxylates, sulfate half-esters, or primary amines were biologically inert. No effect of particle source or length was observed in the in-vitro and in-vivo studies conducted. The lack of in-vitro or in-vivo immune response toward charged CNCs in these experiments supports their use in future biological studies.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

ENIGMA: Ecosystems and Networks Integrated with Genes and Molecular Assemblies. Final Report

ENIGMA research is performed at a very large scale involving collaborations between multiple research groups to address two major driving concepts: For any microbe, it is possible to discover efficiently the genetic determinants of adaptation to life in dynamic environments in contact with other living members of its ecology and reveal hidden functional phenomena that are only possible by using a systems biology approach; and for any environment, it is possible to predict the temporal changes in geochemistry and accompanying system behavior, for some length of time, given biogeochemical and physical inputs. These driving concepts also map directly to grand challenges the ENIGMA team has outlined: “Define the levels of biological organization most relevant to scaling from single cells to ecosystems and global cycles; capture how that organization varies in time and space; and identify critical interactions that dictate rates of carbon, nutrient, and energy transformation in different environments.”

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics

Biological systems are composed of heterogeneous populations of cells that intercommunicate to form a functional living tissue. Biological function varies greatly across populations of cells, as each single cell has a unique transcriptome, proteome, and metabolome that translates to functional differences within single species and across kingdoms. Over the past decade, substantial advancements in our ability to characterize omic profiles on a single cell level have occurred, including in multiple spectroscopic and mass spectrometry (MS)-based techniques. Of these technologies, spatially resolved mass spectrometry approaches, including mass spectrometry imaging (MSI), have shown the most progress for single cell proteomics and metabolomics. For example, reporter-based methods using heavy metal tags have allowed for targeted MS investigation of the proteome at the subcellular level, and development of technologies such as laser ablation electrospray ionization mass spectrometry (LAESI-MS) now mean that dynamic metabolomics can be performed in situ. In this Perspective, we showcase advancements in single cell spatial metabolomics and proteomics over the past decade and highlight important aspects related to high-throughput screening, data analysis, and more which are vital to the success of achieving proteomic and metabolomic profiling at the single cell scale. Finally, using this broad literature summary, we provide a perspective on how the next decade may unfold in the area of single cell MS-based proteomics and metabolomics.

59 BASIC BIOLOGICAL SCIENCES↗

Disruption of Very-Long-Chain-Fatty Acid Synthesis Has an Impact on the Dynamics of Cellulose Synthase in Arabidopsis thaliana

In higher plants, cellulose is synthesized by membrane-spanning large protein complexes named cellulose synthase complexes (CSCs). In this study, the Arabidopsis PASTICCINO2 (PAS2) was identified as an interacting partner of cellulose synthases. PAS2 was previously characterized as the plant 3-hydroxy-acyl-CoA dehydratase, an ER membrane-localized dehydratase that is essential for very-long-chain-fatty acid (VLCFA) elongation. The pas2-1 mutants show defective cell elongation and reduction in cellulose content in both etiolated hypocotyls and light-grown roots. Although disruption of VLCFA synthesis by a genetic alteration had a reduction in VLCFA in both etiolated hypocotyls and light-grown roots, it had a differential effect on cellulose content in the two systems, suggesting the threshold level of VLCFA for efficient cellulose synthesis may be different in the two biological systems. pas2-1 had a reduction in both CSC delivery rate and CSC velocity at the PM in etiolated hypocotyls. Interestingly, Golgi but not post-Golgi endomembrane structures exhibited a severe defect in motility. Experiments using pharmacological perturbation of VLCFA content in etiolated hypocotyls strongly indicate a novel function of PAS2 in the regulation of CSC and Golgi motility. Through a combination of genetic, biochemical and cell biology studies, our study demonstrated that PAS2 as a multifunction protein has an important role in the regulation of cellulose biosynthesis in Arabidopsis hypocotyl.

59 BASIC BIOLOGICAL SCIENCES↗

Stochastic Effects in Computational Biology of Space Radiation Cancer Risk

Estimating risk from space radiation poses important questions on the radiobiology of protons and heavy ions. We are considering systems biology models to study radiation induced repair foci (RIRF) at low doses, in which less than one-track on average transverses the cell, and the subsequent DNA damage processing and signal transduction events. Computational approaches for describing protein regulatory networks coupled to DNA and oxidative damage sites include systems of differential equations, stochastic equations, and Monte-Carlo simulations. We review recent developments in the mathematical description of protein regulatory networks and possible approaches to radiation effects simulation. These include robustness, which states that regulatory networks maintain their functions against external and internal perturbations due to compensating properties of redundancy and molecular feedback controls, and modularity, which leads to general theorems for considering molecules that interact through a regulatory mechanism without exchange of matter leading to a block diagonal reduction of the connecting pathways. Identifying rate-limiting steps, robustness, and modularity in pathways perturbed by radiation damage are shown to be valid techniques for reducing large molecular systems to realistic computer simulations. Other techniques studied are the use of steady-state analysis, and the introduction of composite molecules or rate-constants to represent small collections of reactants. Applications of these techniques to describe spatial and temporal distributions of RIRF and cell populations following low dose irradiation are described.

Cucinotta, Francis A.↗

Radiation Quality Effects on Transcriptome Profiles in 3-D Cultures After Charged Particle Irradiation

In this work, we evaluated the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Current risk models for assessment of space radiation-induced cancer have large uncertainties because the models for adverse health effects following radiation exposure are founded on epidemiological analyses of human populations exposed to low-LET radiation. Reducing these uncertainties requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. In order to better quantify these radiation quality effects in biological systems, we are utilizing novel 3-D organotypic human tissue models for space radiation research. These models hold promise for risk assessment as they provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information.

Patel, Zarana S.↗