Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Biologically plausible”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

120 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Effects of chronic low-dose radiation on cataract prevalence and characterization in wild boar (Sus scrofa) from Fukushima, Japan

This study evaluated cataracts in wild boar exposed to chronic low-dose radiation. We examined wild boar from within and outside the Fukushima Exclusion Zone for nuclear, cortical, and posterior subcapsular (PSC) cataracts in vivo and photographically. Plausible upper-bound, lifetime radiation dose for each boar was estimated from radioactivity levels in each animal’s home range combined with tissue concentrations of 134+137Cesium. Fifteen exposed and twenty control boar were evaluated. There were no significant differences in overall prevalence or score for cortical or PSC cataracts between exposed and control animals. Nuclear (centrally located) cataracts were significantly more prevalent in exposed boar (p<0.05) and had statistically higher median scores. Plausible upper-bound, lifetime radiation dose ranged from 1 to 1,600 mGy in exposed animals, with no correlation between dose and cortical or PSC score. While radiation dose and nuclear score were positively associated, the impact of age could not be completely separated from the relationship. Additionally, the clinical significance of even the highest scoring nuclear cataract was negligible. Based on the population sampled, wild boar in the Fukushima Exclusion Zone do not have a significantly higher prevalence or risk of cortical or PSC cataracts compared to control animals.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2025

Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis

A complete understanding of enzyme mechanisms requires atomistic details of chemical reactions. Quantum-based molecular dynamics simulations (QMD) are a potential source of this information, but trade-offs between accuracy and computational cost have limited their use. We previously developed extended Lagrangian Born–Oppenheimer molecular dynamics (XL-BOMD) methods that leverage a negligible compromise in accuracy to substantially decrease the cost of QMD simulations. Here, we develop a reactive QMD approach using the latest XL-BOMD formulation, which enables efficient simulations of highly reactive systems, and use it to investigate mechanisms of intermediate formation in isocyanide hydratase (ICH) catalysis. In QMD simulations, molecular analogs of ICH active site residues reacted with para-nitrophenyl isocyanide, forming a thioimidate. Analysis of simulated atomic configurational and charge dynamics revealed a pathway where protonation of the isocyanide carbon occurs prior to thioimidate formation and suggested a possible role of Asp17 as a proton donor in the early phase of ICH catalysis. To test whether the pathway seen using the reactive QMD approach might be relevant to ICH catalysis, we performed X-ray crystallography and pre-steady-state enzyme kinetics studies of wild-type and D17N mutant ICH. Both the structure and kinetics are sensitive to the D17N mutation in a manner that is consistent with the order of the reaction steps seen in the simulations. Mobile protons play essential roles in many enzymes, yet they are difficult to observe experimentally, making the ordering of proton-dependent steps ambiguous in many enzyme mechanisms. The ability to directly simulate model reactions for the design of experiments that provide information about enzyme mechanisms involving mobile protons demonstrates the significance of our reactive QMD approach and motivates further biological applications.

36 MATERIALS SCIENCE↗
DOE OSTI2025

The Role of Bedrock Circulation Depth and Porosity in Mountain Streamflow Response to Prolonged Drought

Quantitative understanding is lacking on how the depth of active groundwater circulation in bedrock affects mountain streamflow response to a multi-year drought. We use an integrated hydrological model to explore the sensitivity of a variety of streamflow metrics to bedrock circulation depth and porosity under a plausible extreme drought scenario lasting up to 5 years. Endmember depth versus hydraulic conductivity relationships and porosity values for fractured crystalline rock are simulated. With drought, a deeper circulation system with higher drainable porosity more effectively buffers minimum flow and significantly limits perennial stream loss in comparison to a shallow circulation system. Streamflow buffering is accomplished through extensive groundwater storage loss. However, deeper circulation systems experience prolonged recovery from drought in comparison to storage-limited shallow systems. Research highlights the importance of characterizing the deeper bedrock hydrogeology in mountainous watersheds to better understand and predict drought impacts on stream ecosystem health and water resource sustainability.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1995

A Strategy for Mars Exopaleontology

There is compelling geological evidence that the climate of early Mars was much more Earth-like, with a denser atmosphere and abundant surface water. Given that life developed on the Earth very quickly (between 4.2 and 3.5 Ga), it is quite plausible that life may have also developed on Mars during this early clement period. If Martian life developed, it is likely to have left behind a fossil record. Thus, an important focus for upcoming Mars missions is to explore for an ancient biosphere. This presents a set of goals and problems that are quite distinct from Exobiology. I call this new activity "Exopaleontology", whose core principles derive from studies of the Precambrian fossil record on Earth, biosedimentology and microbial fossilization. Such studies reveal that the most important factor favoring the long-term preservation of microbial fossils is rapid entombment of microorganisms by fine-grained, stable mineral phases such as silica, phosphate, carbonate and metal sulfides. Terrestrial environments where such aqueous mineral phases frequently entomb and preserve microorganisms include subaerial and subaqueous springs and shallow hydrothermal systems, evaporitic alkaline lakes, "hardpan" soils (e.g. calcretes, silcretes, ferracretes), and frozen soils or ground ice. With the exception of ice, which has a short crustal residence time, such deposits am known to retain a record of terrestrial life for billions of years. Current activities seek to refine and apply this strategy to the Mars Global Surveyor missions and beyond. Ongoing studies of microbial fossilization in each of the target environments identified above are aimed at improving our understanding of how biological information is incorporated into aqueous mineral deposits and preserved. Viking data is being used to target sites for high resolution orbital imaging and spectroscopy during upcoming Mars missions. Such data will provide a basis for selecting sites for future landed missions and eventually, sample return.

Farmer, Jack D.↗
NASA NTRS2002

Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog

Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice. Mice were divided into three housing groups: group, isolation, and AOS. Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil-supplemented CD for the 1-wk duration of the experiments. In AOS mice, supplemental nucleotides significantly increased in vivo lymph node proliferation and ex vivo lymphoproliferation response to alloantigen and mitogens, respectively, and interleukin-2 and interferon-gamma production. A lower corticosterone level was observed in uracil-supplemented CD compared with CD. These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response during the microgravity analog conditions.

NASA Center JSC↗
DOE OSTI2024

Structural insights into the unexpected agonism of tetracyclic antidepressants at serotonin receptors 5-HT 1e R and 5-HT 1F R

Serotonin [5-hydroxytryptamine (5-HT)] acts via 13 different receptors in humans. Of these receptor subtypes, all but 5-HT 1e R have confirmed roles in native tissue and are validated drug targets. Despite 5-HT 1e R’s therapeutic potential and plausible druggability, the mechanisms of its activation remain elusive. To illuminate 5-HT 1e R’s pharmacology in relation to the highly homologous 5-HT 1F R, we screened a library of aminergic receptor ligands at both receptors and observe 5-HT 1e R/5-HT 1F R agonism by multicyclic drugs described as pan-antagonists at 5-HT receptors. Potent agonism by tetracyclic antidepressants mianserin, setiptiline, and mirtazapine suggests a mechanism for their clinically observed antimigraine properties. Using cryo-EM and mutagenesis studies, we uncover and characterize unique agonist-like binding poses of mianserin and setiptiline at 5-HT 1e R distinct from similar drug scaffolds in inactive-state 5-HTR structures. Together with computational studies, our data suggest that these binding poses alongside receptor-specific allosteric coupling in 5-HT 1e R and 5-HT 1F R contribute to the agonist activity of these antidepressants.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2011

The Impact of Rise of the Andes and Amazon Landscape Evolution on Diversification of Lowland terra-firme Forest Birds

Since the 19th Century, the unmatched biological diversity of Amazonia has stimulated a diverse set of hypotheses accounting for patterns of species diversity and distribution in mega-diverse tropical environments. Unfortunately, the evidence supporting particular hypotheses to date is at best described as ambiguous, and no generalizations have emerged yet, mostly due to the lack of comprehensive comparative phylogeographic studies with thorough trans-Amazonian sampling of lineages. Here we report on spatial and temporal patterns of diversification estimated from mitochondrial gene trees for 31 lineages of birds associated with upland terra-firme forest, the dominant habitat in modern lowland Amazonia. The results confirm the pervasive role of Amazonian rivers as primary barriers separating sister lineages of birds, and a protracted spatio-temporal pattern of diversification, with a gradual reduction of earlier (1st and 2nd) and older (> 2 mya) splits associated with each lineage in an eastward direction. (The easternmost tributaries of the Amazon, the Xingu and Tocantins Rivers, are not associated with any splits older than > 2 mya). For the suboscine passerines, maximum-likelihood estimates of rates of diversification point to an overall constant rate over the past 5 my (up to a significant downturn at 300,000 y ago). This "younging-eastward" pattern may have an abiotic explanation related to landscape evolution. Triggered by a new pulse of Andean uplift, it has been proposed that modern Amazon basin landscapes may have evolved successively eastward, away from the mountain chain, starting approximately 10 mya. This process was likely based on the deposition of vast fluvial sediment masses, known as megafans, that may have extended progressively and in series eastward from Andean sources. This process plausibly explains the progressive extinction of original Pebas wetland of western-central Amazonia by the present fluvial landsurfaces of a more terra-firme type. The youngest landsurfaces thus lie furthest from the mountains. In this scenario major drainages were also reoriented in wholesale fashion away from a northerly orientation generally towards the east and an Atlantic Ocean outlet. The advance of megafans is best seen by the location of axial rivers such as the Orinoco and Mamore which lie against the cratonic margins furthest from the Andes, at the distal ends of major megafan ramparts. More importantly, other major river courses in western-central Amazonia will have been established at progressively younger dates with distance eastward. If this landscape-sequence scenario is accurate, it parallels the progressive younging of the passerine lineages. The bird DNA data appears to confirm strongly the pervasive role of Amazonian rivers--as primary barriers separating sister lineages of birds, and thus probably as facilitaters of bird speciation. We show for the first time that a general spatio-temporal pattern of diversification for terra-firme lineages in the Amazon is associated with rivers ("younging-eastward"), and furthermore parallels a specific scenario of regional drainage evolution.

Aleixo, Alexandre↗
DOE OSTI2026

Dara: Automated Multiple-Hypothesis Phase Identification and Refinement from Powder X-ray Diffraction

Powder X-ray diffraction (XRD) is a foundational technique for characterizing crystalline materials. However, the reliable interpretation of XRD patterns, particularly in multiphase systems, remains a manual and expertise-demanding task. As a characterization method that only provides structural information, multiple reference phases can often be fit to a single pattern, leading to potential misinterpretation when alternative solutions are overlooked. To ease humans’ efforts and address the challenge, we introduce Dara (data-driven automated Rietveld analysis), a framework designed to automate the robust identification and refinement of multiple phases from powder XRD data. Dara performs an exhaustive tree search over all plausible phase combinations within a given chemical space and validates each hypothesis using the BGMN Rietveld refinement routine. Key features include structural database filtering, automatic clustering of isostructural phases during tree expansion, and peak-matching-based scoring to identify promising phases for refinement. When ambiguity exists, Dara generates multiple hypothesis which can then be decided between by human experts or with further characterization tools. By enhancing the reliability and accuracy of phase identification, Dara enables scalable analysis of realistic complex XRD patterns and provides a foundation for integration into multimodal characterization workflows, moving toward fully self-driving materials discovery.

Biological databases↗
DOE OSTI2021

Mycobacterium tuberculosis Phe-tRNA synthetase: structural insights into tRNA recognition and aminoacylation

Abstract Tuberculosis, caused by Mycobacterium tuberculosis, responsible for ∼1.5 million fatalities in 2018, is the deadliest infectious disease. Global spread of multidrug resistant strains is a public health threat, requiring new treatments. Aminoacyl-tRNA synthetases are plausible candidates as potential drug targets, because they play an essential role in translating the DNA code into protein sequence by attaching a specific amino acid to their cognate tRNAs. We report structures of M. tuberculosis Phe-tRNA synthetase complexed with an unmodified tRNAPhe transcript and either L-Phe or a nonhydrolyzable phenylalanine adenylate analog. High-resolution models reveal details of two modes of tRNA interaction with the enzyme: an initial recognition via indirect readout of anticodon stem-loop and aminoacylation ready state involving interactions of the 3′ end of tRNAPhe with the adenylate site. For the first time, we observe the protein gate controlling access to the active site and detailed geometry of the acyl donor and tRNA acceptor consistent with accepted mechanism. We biochemically validated the inhibitory potency of the adenylate analog and provide the most complete view of the Phe-tRNA synthetase/tRNAPhe system to date. The presented topography of amino adenylate-binding and editing sites at different stages of tRNA binding to the enzyme provide insights for the rational design of anti-tuberculosis drugs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Application of Multi-Criteria Decision Analysis Techniques for Informing Select Agent Designation and Decision Making

The Centers for Disease Control and Prevention (CDC) Select Agent Program establishes a list of biological agents and toxins that potentially threaten public health and safety, the procedures governing the possession, utilization, and transfer of those agents, and training requirements for entities working with them. Every 2 years the Program reviews the select agent list, utilizing subject matter expert (SME) assessments to rank the agents. In this study, we explore the applicability of multi-criteria decision analysis (MCDA) techniques and logic tree analysis to support the CDC Select Agent Program biennial review process, applying the approach broadly to include non-select agents to evaluate its generality. We conducted a literature search for over 70 pathogens against 15 criteria for assessing public health and bioterrorism risk and documented the findings for archiving. The most prominent data gaps were found for aerosol stability and human infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. Analysis of results obtained from a two-dimensional plot of weighted scores for difficulty of attack (i.e., exposure and production criteria) vs. consequences of an attack (i.e., consequence and mitigation criteria) provided greater fidelity for understanding agent placement compared to a 1-to-n ranking and was used to define a region in the upper right-hand quadrant for identifying pathogens for consideration as select agents. A sensitivity analysis varied the numerical weights attributed to various properties of the pathogens to identify potential quantitative (x and y) thresholds for classifying select agents. The results indicate while there is some clustering of agent scores to suggest thresholds, there are still pathogens that score close to any threshold, suggesting that thresholding “by eye” may not be sufficient. The sensitivity analysis indicates quantitative thresholds are plausible, and there is good agreement of the analytical results with select agent designations. A second analytical approach that applied the data using a logic tree format to rule out pathogens for consideration as select agents arrived at similar conclusions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Life history strategies among soil bacteria—dichotomy for few, continuum for many

Abstract Study of life history strategies may help predict the performance of microorganisms in nature by organizing the complexity of microbial communities into groups of organisms with similar strategies. Here, we tested the extent that one common application of life history theory, the copiotroph-oligotroph framework, could predict the relative population growth rate of bacterial taxa in soils from four different ecosystems. We measured the change of in situ relative growth rate to added glucose and ammonium using both 18O–H2O and 13C quantitative stable isotope probing to test whether bacterial taxa sorted into copiotrophic and oligotrophic groups. We saw considerable overlap in nutrient responses across most bacteria regardless of phyla, with many taxa growing slowly and few taxa that grew quickly. To define plausible life history boundaries based on in situ relative growth rates, we applied Gaussian mixture models to organisms’ joint 18O–13C signatures and found that across experimental replicates, few taxa could consistently be assigned as copiotrophs, despite their potential for fast growth. When life history classifications were assigned based on average relative growth rate at varying taxonomic levels, finer resolutions (e.g., genus level) were significantly more effective in capturing changes in nutrient response than broad taxonomic resolution (e.g., phylum level). Our results demonstrate the difficulty in generalizing bacterial life history strategies to broad lineages, and even to single organisms across a range of soils and experimental conditions. We conclude that there is a continued need for the direct measurement of microbial communities in soil to advance ecologically realistic frameworks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Metabolic rewiring and biomass redistribution enable optimized mixotrophic growth in Chlamydomonas

Aquatic photosynthetic systems account for approximately one-half of all global carbon assimilation and could be a significant source of renewable fuels and feedstocks. However, rapid growth and biomass production in algae have not always translated into high product yields, partly because central metabolism is context specific, with metabolic fluxes being influenced by nutrient conditions and other environmental factors. In the green microalga Chlamydomonas reinhardtii (Chlamydomonas), mixotrophic cultures (acetate + light) grow far faster than phototrophic (light only) or heterotrophic (acetate + dark) cultures, even though acetate partially suppresses photosynthesis. Here, an isotopic dilution strategy with unlabeled acetate was combined with 13 CO 2 transient labeling to perform isotopically nonstationary metabolic flux analysis (INST-MFA) and to directly compare autotrophic and mixotrophic metabolism in Chlamydomonas supported by data from transcriptomics, proteomics, and metabolomics. INST-MFA indicated that acetate induces a synergistic rewiring of metabolism, conserving carbon by using the glyoxylate cycle and suppressing gluconeogenesis, the latter of which was discordant with omics results and prior models. Additionally, our data provide a plausible rationale for the well-known suppression of photosynthesis by acetate. We propose that reduced total protein content in mixotrophic versus phototrophic cells, much of which is attributed to reduced levels of photosynthetic proteins, decreases the costly metabolic burden of protein synthesis and represents a growth rate optimization strategy.

59 BASIC BIOLOGICAL SCIENCES↗