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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.

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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Monitoring ICAROUS: From Requirements to Autonomous Flight

The Independent Configurable Architecture for Reliable Operations of Unmanned Systems (ICAROUS) is a software architecture incorporating a set of algorithms to enable autonomous operations of unmanned aircraft applications. This paper provides an overview of Monitoring ICAROUS, a project whose objective is to provide a formal approach to generating runtime monitors for autonomous systems from requirements written in a structured natural language. This approach integrates FRET, a formal requirement elicitation and authoring tool, and Copilot, a runtime verification framework. FRET is used to specify formal requirements in structured natural language. These requirements are translated into temporal logic formulae. Copilot is then used to generate executable runtime monitors from these temporal logic specifications. The generated monitors are directly integrated into ICAROUS to perform runtime verification during flight.

Formal Methods↗
NASA NTRS2023

Wildfire-fighting Use Case Requirements to Monitor

In this technical report, we provide requirements for a wildfire-fighting use-case, towards the Safety Demonstrator 1. The use case will incorporate ground and airborne assets operating in a coordinated fashion, and will comprise five activities, from detection to the execution of the initial attack. Depending on the activity and the data involved, the requirements identified may be non-probabilistic or probabilistic. In both cases, we first identify some of the requirements we wish to monitor, and then present a formalization using the language of requirements of the NASA requirements elicitation tool FRET. To formalize probabilistic requirements, we use a novel extension to FRET’s requirements language that incorporates notions of probability, and discuss how requirements can be translated into existing probabilistic temporal logics like PCTL. We exemplify how some of the requirements presented can be monitored using the existing tools Ogma and Copilot. We close with a summary and future directions.

Requirements↗
DOE OSTI2016

Ribosomal targets for antibiotic drug discovery

The present invention relates to methods to identify molecules that binds in the neomycin binding pocket of a bacterial ribosome using structures of an intact bacterial ribosome that reveal how the ribosome binds tRNA in two functionally distinct states, determined by x-ray crystallography. One state positions tRNA in the peptidyl-tRNA binding site. The second, a fully rotated state, is stabilized by ribosome recycling factor (RRF) and binds tRNA in a highly bent conformation in a hybrid peptidyl/exit (P/E) site. Additionally, the invention relates to various assays, including single-molecule assay for ribosome recycling, and methods to identify compounds that interfere with ribosomal function by detecting newly identified intermediate FRET states using known and novel FRET pairs on the ribosome. The invention also provides vectors and compositions with an N-terminally tagged S13 protein.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Clusters of Nanoscale Liposomes Modulate the Release of Encapsulated Species and Mimic the Compartmentalization Intrinsic in Cell Structures

We report the ability to place a high concentration of liposomes in a confined volume as a multicompartment cluster that mimics biological cells and allows for the modulation of release of encapsulated species. The formation of these coated multicompartmental structures is achieved by first binding liposomes into clusters before encapsulating them within a two-dimensional metal–organic framework composed of tannic acid coordinated with a metal ion. The essential feature is a molecularly thin skin over a ssystem of clustered liposomes in a pouch. The structural features of these pouches are revealed by small-angle scattering and electron microscopy. Through cryogenic electron microscopy, clusters with intact liposomes are observed that appear to be encapsulated within a pouch. Small-angle X-ray scattering shows the emergence of a relatively weak Bragg peak at q = 0.125 Å–1, possibly indicating the attachment of the bilayers of adjacent liposomes. The metal–phenolic network (MPN) forms a nanosized conformal coating around liposome clusters, resulting in the reduced release rate of the encapsulated rhodamine B dye. We further show the possibility of communication between the adjacent nanocompartments in the cluster by demonstrating enhanced energy transfer using fluorescence resonance energy transfer (FRET) experiments where the lipophilic donor dye 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) incorporated within one liposomal compartment transfers energy upon excitation to the lipophilic acceptor dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in a neighboring liposomal compartment due to their close proximity within the multicompartmental cluster. As a result, these observations have significance in adapting these multicompartmental structures that mimic biological cells for cascade reactions and as new depot drug delivery systems.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2015

Structural analysis of a class III preQ 1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics

PreQ 1 -III riboswitches are newly identified RNA elements that control bacterial genes in response to preQ 1 (7-aminomethyl-7-deazaguanine), a precursor to the essential hypermodified tRNA base queuosine. Although numerous riboswitches fold as H-type or HL out -type pseudoknots that integrate ligand-binding and regulatory sequences within a single folded domain, the preQ 1 -III riboswitch aptamer forms a HL out -type pseudoknot that does not appear to incorporate its ribosome-binding site (RBS). To understand how this unusual organization confers function, in this paper we determined the crystal structure of the class III preQ 1 riboswitch from Faecalibacterium prausnitzii at 2.75 Å resolution. PreQ 1 binds tightly (K D,app 6.5 ± 0.5 nM) between helices P1 and P2 of a three-way helical junction wherein the third helix, P4, projects orthogonally from the ligand-binding pocket, exposing its stem-loop to base pair with the 3' RBS. Biochemical analysis, computational modeling, and single-molecule FRET imaging demonstrated that preQ 1 enhances P4 reorientation toward P1–P2, promoting a partially nested, H-type pseudoknot in which the RBS undergoes rapid docking (k dock ~0.6 s -1 ) and undocking (k undock ~1.1 s -1 ). Finally, discovery of such dynamic conformational switching provides insight into how a riboswitch with bipartite architecture uses dynamics to modulate expression platform accessibility, thus expanding the known repertoire of gene control strategies used by regulatory RNAs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Asymmetric unwrapping of nucleosomal DNA propagates asymmetric opening and dissociation of the histone core

The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs. We find that H2A–H2B histone dimers are released sequentially, with the first dimer being released after the DNA has formed an asymmetrically unwrapped, teardrop-shape DNA structure. This finding suggests that the octasome-to-hexasome transition is guided by the asymmetric unwrapping of the DNA. Furthermore, the link between DNA structure and histone composition suggests a potential mechanism for the action of proteins that alter nucleosome configurations such as histone chaperones and chromatin remodeling complexes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions

Proteins are marginally stable molecules that fluctuate between folded and unfolded states. Here, we provide a high-resolution description of unfolded states under refolding conditions for the N-terminal domain of the L9 protein (NTL9). We use a combination of time-resolved Förster resonance energy transfer (FRET) based on multiple pairs of minimally perturbing labels, time-resolved small-angle X-ray scattering (SAXS), all-atom simulations, and polymer theory. Upon dilution from high denaturant, the unfolded state undergoes rapid contraction. Although this contraction occurs before the folding transition, the unfolded state remains considerably more expanded than the folded state and accommodates a range of local and nonlocal contacts, including secondary structures and native and nonnative interactions. Paradoxically, despite discernible sequence-specific conformational preferences, the ensemble-averaged properties of unfolded states are consistent with those of canonical random coils, namely polymers in indifferent (theta) solvents. These findings are concordant with theoretical predictions based on coarse-grained models and inferences drawn from single-molecule experiments regarding the sequence-specific scaling behavior of unfolded proteins under folding conditions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

A genetically encoded biosensor reveals spatiotemporal variation in cellular phosphate content in Brachypodium distachyon mycorrhizal roots

Arbuscular mycorrhizal (AM) symbiosis is accompanied by alterations to root cell metabolism and physiology, and to the pathways of orthophosphate (Pi) entry into the root, which increase with Pi delivery to cortical cells via arbuscules. How AM symbiosis influences the Pi content and Pi response dynamics of cells in the root cortex and epidermis is unknown. Using fluorescence resonance energy transfer (FRET)-based Pi biosensors, here we mapped the relative cytosolic and plastidic Pi content of Brachypodium distachyon mycorrhizal root cells, analyzed responses to extracellular Pi and traced extraradical hyphae-mediated Pi transfer to colonized cells. Colonized cortical cells had a higher cytosolic Pi content relative to noncolonized cortical and epidermal cells, while plastidic Pi content was highest in cells at the infection front. Pi application to the entire mycorrhizal root resulted in transient changes in cytosolic Pi that differed in direction and magnitude depending on cell type and arbuscule status; cells with mature arbuscules showed a substantial transient increase in cytosolic Pi while those with collapsed arbuscules showed a decrease. Directed Pi application to extraradical hyphae resulted in measurable changes in cytosolic Pi of colonized cells 18 h after application. Our experiments reveal that cells within a mycorrhizal root vary in Pi content and Pi response dynamics.

32Pi tracing↗
DOE OSTI2011

Modified Ribose Receptor Response in Isolated Diatom Frustules

Diatoms are a distinctive group of microalgae with the unique ability to produce a highly-ordered biosilica matrix, known as the frustule. Diatoms hold significant potential in the biotechnology field as a silica scaffold for embedding proteins. In this study, we analyzed the funtionalization of biosilica with a receptor complex through genetic modification of the diatom, Thalassiosira pseudonana. Through the use of Foerster Resonance Energy Transfer (FRET), the receptor was shown to remain active in transformed frustules after the inner cellular contents were removed. In addition to protein functionality, growth conditions for T. pseudonana were optimized. Untransformed cultures receiving aeration grew more rapidly than stagnant untransformed cultures. Surprisingly, transformed cultures grew more quickly than untransformed cultures. This study demonstrates isolated diatom frustules provide an effective scaffold for embedded receptor complexes. Through this research, we provide the groundwork for the development of new biosensors for use in diagnostics and environmental remediation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

Bridging the Gap Between Requirements and Simulink Model Analysis

Formal veri fication and simulation are powerful tools for the veri fication of requirements against complex systems. Requirements are developed in early stages of the software lifecycle and are typically expressed in natural language. There is a gap between such requirements and their software implementations. We present a framework that bridges this gap by supporting a tight integration and feedback loop between high-level requirements and their analysis against software artifacts. Our framework implements an analysis portal within the fret requirements elicitation tool, thus forming an end-to-end, open-source environment where requirements are written in an intuitive, structured natural language, and are veri fied automatically against Simulink models.

FRET↗
NASA NTRSDate not supplied

Simplifying Requirements Formalization for Resource-Constrained Mission-Critical Software

Developing critical software requires adherence to rigorous software development practices, such as formal requirement specification and verification. Despite their importance, such practices are often considered as complex and challenging tasks that require a strong formal methods background. In this paper, we present our work on simplifying the formal requirements specification experience for resource-constrained mission critical software through the use of structured natural language. To this end, we connect NASA’s FRET, a formal requirement elicitation and authoring tool with the Shelley model checking framework for MicroPython code. We report our experience on using these tools to specify requirements and analyze code from the NASA Ames PHALANX exploration concept.

PHALANX exploration concept↗
NASA NTRSDate not supplied

Design, Formalization, and Verification of Decision Making for Intelligent Systems

The development of autonomous systems requires a rigorous process that can guarantee a system’s reliability in critical applications. At its core, an autonomous system bases its behavior on a well-defined decision making system. In this paper, we present a methodological basis for the design, formalization and formal verification of Decision Making systems for autonomous agents. The approach is generally applicable to operational objectives that can be functionally decomposed and subsequently represented as Hierarchical Finite State Machines. As a case study, we present the application of this method to implement a Decision Making model in Simulink. Furthermore, we present how we use NASA’s FRET tool to write requirements in structured natural language and generate formal specifications that can be automatically digested by NASA’s CoCoSim tool. Finally, we present how, by leveraging CoCoSim, we perform formal verification against the Simulink model and present analysis results.

Model-based development↗
DOE OSTI2021

Highly Efficient Ternary Solar Cells with Efficient Förster Resonance Energy Transfer for Simultaneously Enhanced Photovoltaic Parameters

Introducing a third component into organic bulk heterojunction solar cells has become an effective strategy to improve photovoltaic performance. Meanwhile, the rapid development of non-fullerene acceptors (NFAs) has pushed the power conversion efficiency (PCE) of organic solar cells (OSCs) to a higher standard. In this study, a series of fullerene-free ternary solar cells are fabricated based on a wide bandgap acceptor, IDTT-M, together with a wide bandgap donor polymer PM6 and a narrow bandgap NFA Y6. Insights from the morphological and electronic characterizations reveal that IDTT-M has been incorporated into Y6 domains without disrupting its molecular packing and sacrificing its electron mobility and work synergistically with Y6 to regulate the packing pattern of PM6, leading to enhanced hole mobility and suppressed recombination. IDTT-M further functions as an energy-level mediator that increases open-circuit voltage ( V OC ) in ternary devices. In addition, efficient Förster resonance energy transfer (FRET) between IDTT-M and Y6 provides a non-radiative pathway for facilitating exciton dissociation and charge collection. As a result, the optimized ternary device features a significantly improved PCE up to 16.63% with simultaneously enhanced short-circuit current ( J SC ), V OC , and fill factor (FF).

36 MATERIALS SCIENCE↗
DOE OSTI2023

Development of the Safe and Broad‐Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained α, γ‐AA Peptide Scaffold

Abstract SARS‐CoV‐2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (M pro ) is essential in the replication of SARS‐CoV‐2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics‐constrained α, γ‐AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the M pro of SARS‐CoV‐2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET‐based M pro enzymatic assay not only for the M pro of SARS‐CoV‐2 but also for SARS‐CoV and MERS‐CoV, along with HCoVs like HCoV‐OC43, HCoV‐229E, HCoV‐NL63 and HKU1. The X‐ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS‐CoV‐2. Overall, the results suggest that α, γ‐AA peptide could be a promising molecular scaffold in designing novel M pro inhibitors of SARS‐CoV‐2 and other coronaviruses.

Chemistry↗
DOE OSTI2023

Integrated data-driven and experimental approaches to accelerate lead optimization targeting SARS-CoV- 2 main protease

Identification of potential therapeutic candidates can be expedited by integrating computational modeling with domain aware machine learning (ML) approaches followed by experimental validation. Generative deep learning models have been recently developed that can generate thousands of new candidates, but their physiochemical properties are typically not optimized. Using our deep learning models and a scaffold as a starting point, we generated tens of thousands of compounds for SARS-CoV-2 M pro that preserve the core scaffold. Here we utilized and implemented several computational tools such as structural alert and toxicity analysis, high throughput virtual screening, ML-based 3D quantitative structure–activity relationships, multi-parameter optimization, and graph neural networks on libraries of generated candidates to predict biological activity and binding affinity a priori. From these collective computational results, eight promising candidates were identified and tested experimentally using Native Mass Spectrometry (MS) and FRET-based functional assays. Two compounds, with quinazoline-2-thiol and acetylpiperidine core moiety showed IC 50 values in the low micromolar range: 2.95±0.0017 µM and 3.41±0.0015 µM, respectively. The molecular dynamics simulations further highlight that binding of these compounds results in allosteric modulations in the chain B and the interface domains of the M pro . The key fragments from these top hits can be used as input for closed loop lead optimization in the integrated pipeline.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Fluorescent Labeling of Protein Using Blue-Emitting 8-Amino-BODIPY Derivatives

8-Amino-BODIPY (boron-dipyrromethane) dyes show bright blue fluorescence. Disclosed here are synthesis and characterization of the photophysical properties of a series of functionalized 8-Amino-BODIPY (BP1–4) for protein labeling. The compact structure and solvent-insensitive absorption property of the dye are desirable features for protein labeling. For the model protein, bovine serum albumin (BSA), the labeling proceeds under mild condition via amide bond formation or thiol-ene conjugation with maintaining the bright blue fluorescence. The chromatography and mass spectroscopy analysis clearly support the labeling of the BODIPY dye on the BSA. The protein labeling with blue-emitting BODIPY would be applicable for studying protein dynamics and fluorescence resonance energy transfer (FRET) with intrinsic biomolecules.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Fluorescence Investigations on Interactions between 7,8-benzo-4-azidomethyl Coumarin and Ortho- and Para-phenylenediamines in Binary Solvent Mixtures of THF and Water

Fluorescence investigations on interactions between 7,8-benzo-4-azidomethyl coumarin (7BAMC) and quenchers ortho-phenylenediamine (OPD) and para-phenylenediamines (PPD) in binary solvent mixtures (THF + water) have been reported. UV-absorption study indicated a weak hydrophobic interaction between 7BAMC and the para isomer. NMR spectral studies indicated the presence of an interaction between 7BAMC and PPD. Magnitudes of the parameters associated with FRET, showed the presence of interactions between 7BAMC and PPD quencher is more predominant than OPD. Fluorescence quenching studies reveal the role of static and dynamic quenching pathways, depending upon Stern–Volmer constant, dielectric constant and dominant non-radiative processes. Binding equilibria analysis indicates a strong interaction between 7BAMC and PPD than OPD and formation of H-bonding. Based on the magnitudes of free energy, enthalpy change and entropy, bimolecular interaction process may be considered as spontaneous and hydrophobic.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Photophysics of “Floppy” Dyads as Potential Biomembrane Probes

In the study a dyad (C6 probe), constructed of two dyes with highly different hydrophobicities, was investigated by steady-state and time-resolved spectroscopic techniques in chloroform, methanol, and in phospholipid vesicles, respectively. The dyad was built on two dyes: the lipophilic benzo[a]pyrene (BaP) and the hydrophilic sulforhodamine B (SRB). The dyes were linked via a short, but flexible alkyl chain (six C-atoms). Based on their spectroscopic properties, BaP and SRB showed a very efficient non-radiative resonance energy transfer in solution. Incorporation into a lipid bilayer limited the relative flexibility (degree of freedom) between donor and acceptor and was used for the investigation of fundamental photophysical aspects (especially of FRET) as well as to elucidate the potential of the dyad to probe the interface of vesicles (or cells). The location of the two dyes in vesicles and their respective accessibility for interactions with dye-specific antibodies was investigated. Based on the alteration of the anisotropy, on the rotational correlation time as well as on the diffusion coefficient the incorporation of the C6 probe into the vesicles was evaluated. Especially the limitation in the relative movements of the two dyes was considered and used to differentiate between potential parameters, that influence the energy transfer in the dyad. Transient absorption spectroscopy (TAS) and pulsed-interleave single molecule fluorescence experiments were performed to better understand the intramolecular interactions in the dyad. Finally, in a showcase for a biosensing application of the dyads, the binding of an SRB-specific antibody was investigated when the dyad was incorporated in vesicles. .

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗