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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 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs

Abstract The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition molecule C1q bound to a tetrameric assembly of proteases C1r and C1s. Enzymatically active C1s provides the catalytic basis for cleavage of the downstream CP components, C4 and C2, and is therefore an attractive target for therapeutic intervention in CP-driven diseases. Although an anti-C1s mAb has been Food and Drug Administration approved, identifying small-molecule C1s inhibitors remains a priority. In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a K d of ∼9.8 μM and competitively inhibits its activity with an inhibition constant (K i) of ∼5.8 μM. A 1.8-Å-resolution crystal structure revealed the physical basis for C1s inhibition by A1 and provided information on the structure–activity relationship of the A1 scaffold, which was supported by evaluating a panel of A1 analogs. Taken together, our work identifies A1 as a new class of small-molecule C1s inhibitor and lays the foundation for development of increasingly potent and selective A1 analogs for both research and therapeutic purposes.

Immunology↗
DOE OSTI2022

Universally Accessible Structural Data on Macromolecular Conformation, Assembly, and Dynamics by Small Angle X-Ray Scattering for DNA Repair Insights.

Structures provide a critical breakthrough step for biological analyses, and small angle X-ray scattering (SAXS) is a powerful structural technique to study dynamic DNA repair proteins. As toxic and mutagenic repair intermediates need to be prevented from inadvertently harming the cell, DNA repair proteins often chaperone these intermediates through dynamic conformations, coordinated assemblies, and allosteric regulation. By measuring structural conformations in solution for both proteins, DNA, RNA, and their complexes, SAXS provides insight into initial DNA damage recognition, mechanisms for validation of their substrate, and pathway regulation. Here, we describe exemplary SAXS analyses of a DNA damage response protein spanning from what can be derived directly from the data to obtaining super resolution through the use of SAXS selection of atomic models. We outline strategies and tactics for practical SAXS data collection and analysis. Making these structural experiments in reach of any basic and clinical researchers who have protein, SAXS data can readily be collected at government-funded synchrotrons, typically at no cost for academic researchers. In addition to discussing how SAXS complements and enhances cryo-electron microscopy, X-ray crystallography, NMR, and computational modeling, we furthermore discuss taking advantage of recent advances in protein structure prediction in combination with SAXS analysis.

Chinnam, Naga Babu↗
DOE OSTI2022

Gate-Tunable Proximity Effects in Graphene on Layered Magnetic Insulators

The extreme versatility of van der Waals materials derives from their ability to exhibit new electronic properties when assembled in proximity with dissimilar crystals. 1 For example, although graphene is inherently non-magnetic, recent work has reported a magnetic proximity effect in graphene interfaced with magnetic substrates, potentially enabling a pathway towards achieving a high-temperature quantum anomalous Hall effect. Here, we investigate heterostructures of graphene and chromium trihalide magnetic insulators (CrI 3 , CrBr 3 , and CrCl 3 ). Surprisingly, we are unable to detect a magnetic exchange field in the graphene, but instead discover proximity effects featuring unprecedented gate-tunability. The graphene becomes highly hole-doped due to charge transfer from the neighboring magnetic insulator, and further exhibits a variety of atypical gate-dependent transport features. The charge transfer can additionally be altered upon switching the magnetic states of the nearest CrI 3 layers. In conclusion, our results provide a roadmap for exploiting proximity effects arising in graphene coupled to magnetic insulators.

2D magnet↗
DOE OSTI2026

Encapsulation in a Bacterial Microcompartment Shell Improves Thermal Stability of a Glycolytic Enzyme

Selective encapsulation of target enzymes is an increasingly well-studied field, with a host of potential applications for biotechnology. Natively, many bacteria utilize bacterial microcompartments (BMCs) for enzyme encapsulation to enhance catalysis. BMCs are protein shells that enable selective localization of targeted metabolic enzymes and may improve catalytic rates by colocalizing pathway enzymes and/or serve to sequester toxic or volatile intermediates. The microcompartment shell of Haliangium ochraceum (HO) is a notable BMC chassis because of its modularity and versatility; it is easily expressed and assembled outside its native host and can accept a wide array of cargo. Recently, it was demonstrated that assembly of HO BMC shells can be easily achieved in vitro. Following up on our previous work on in vivo assembly of HO-BMCs with triose phosphate isomerase (TPI) as a model enzyme cargo, here we have demonstrated the advantages of in vitro assembly (IVA) for targeted enzyme encapsulation. We achieved variable loading of BMC shells with targeted amounts of TPI and demonstrated enhanced thermal stability of encapsulated TPI versus free TPI up to 62 °C.

assays↗
DOE OSTI2020

Data from A Genetic Toolbox for Metabolic Engineering of Issatchenkia orientalis

The nonconventional yeast Issatchenkia orientalis can grow under highly acidic conditions and has been explored for production of various organic acids. However, its broader application is hampered by the lack of efficient genetic tools to enable sophisticated metabolic manipulations. We recently constructed an episomal plasmid based on the autonomously replicating sequence (ARS) from Saccharomyces cerevisiae (ScARS) in I. orientalis and developed a CRISPR/Cas9 system for multiplexed gene deletions. Here we report three additional genetic tools including: (1) identification of a 0.8 kb centromere-like (CEN-L) sequence from the I. orientalis genome by using bioinformatics and functional screening; (2) discovery and characterization of a set of constitutive promoters and terminators under different culture conditions by using RNA-Seq analysis and a fluorescent reporter; and (3) development of a rapid and efficient in vivo DNA assembly method in I. orientalis , which exhibited ~100% fidelity when assembling a 7 kb-plasmid from seven DNA fragments ranging from 0.7 kb to 1.7 kb. As proof of concept, we used these genetic tools to rapidly construct a functional xylose utilization pathway in I. orientalis .

Conversion↗
DOE OSTI2021

Co-expression networks in Chlamydomonas reveal significant rhythmicity in batch cultures and empower gene function discovery

The unicellular green alga Chlamydomonas reinhardtii is a choice reference system for the study of photosynthesis and chloroplast metabolism, cilium assembly and function, lipid and starch metabolism, and metal homeostasis. Despite decades of research, the functions of thousands of genes remain largely unknown, and new approaches are needed to categorically assign genes to cellular pathways. Growing collections of transcriptome and proteome data now allow a systematic approach based on integrative co-expression analysis. We used a dataset comprising 518 deep transcriptome samples derived from 58 independent experiments to identify potential co-expression relationships between genes. We visualized co-expression potential with the R package corrplot, to easily assess co-expression and anti-correlation between genes. We extracted several hundred high-confidence genes at the intersection of multiple curated lists involved in cilia, cell division, and photosynthesis, illustrating the power of our method. Surprisingly, Chlamydomonas experiments retained a significant rhythmic component across the transcriptome, suggesting an underappreciated variable during sample collection, even in samples collected in constant light. Our results therefore document substantial residual synchronization in batch cultures, contrary to assumptions of asynchrony. We provide step-by-step protocols for the analysis of co-expression across transcriptome data sets from Chlamydomonas and other species to help foster gene function discovery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Taxonomic and carbon metabolic diversification of Bathyarchaeia during its coevolution history with early Earth surface environment

Bathyarchaeia, as one of the most abundant microorganisms on Earth, play vital roles in the global carbon cycle. However, our understanding of their origin, evolution, and ecological functions remains poorly constrained. Here, we present the largest dataset of Bathyarchaeia metagenome assembled genome to date and reclassify Bathyarchaeia into eight order-level units corresponding to the former subgroup system. Highly diversified and versatile carbon metabolisms were found among different orders, particularly atypical C1 metabolic pathways, indicating that Bathyarchaeia represent overlooked important methylotrophs. Molecular dating results indicate that Bathyarchaeia diverged at ~3.3 billion years, followed by three major diversifications at ~3.0, ~2.5, and ~1.8 to 1.7 billion years, likely driven by continental emergence, growth, and intensive submarine volcanism, respectively. The lignin-degrading Bathyarchaeia clade emerged at ~300 million years perhaps contributed to the sharply decreased carbon sequestration rate during the Late Carboniferous period. The evolutionary history of Bathyarchaeia potentially has been shaped by geological forces, which, in turn, affected Earth’s surface environment.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

rHealth One Demonstration Aboard ISS: A Microfluidic Bioanalyzer Based on Sheath/Hydrodynamic Focusing Flow Cytometry

The Exploration Medical Capability (ExMC) element aims to provide astronauts with the means for their own health monitoring, diagnosis, and treatment during exploration missions. As space flight ventures further from earth, the need for autonomous medical care increases under greater constraints on size, mass, and resources. One pillar for diagnosis that crew would be separated from is laboratory analysis. Even now on ISS, blood samples must be collected and returned to earth for testing. In response, ExMC is assessing how assays for hematology, bone health, radiation exposure etc. could be addressed through commercial-off-the-shelf (COTS) and Small Business Innovation Research (SBIR) funded bioanalyzers that are miniaturizing lab technology. Since missions will reach distances where there are no timely replacements, validation on the International Space Station (ISS) is a necessary part of that assessment. In partnership with NASA Johnson Space Center (JSC) Immunology Lab and the Research Operations and Integration (ROI) element, ExMC conducted a technology demonstration on ISS of the rHEALTH ONE, a flow cytometry based bioanalyzer, to assess future devices based on this design. In flow cytometry, there are predominantly three ways to focus the cells (or particles) into a single file stream: hydrodynamic focusing, microcapillary, and acoustic focusing. The rHEALTH ONE utilizes the commercial standard, sheath-based hydrodynamic focusing. rHEALTH itself represents both a company and a suite of medical tools NASA has funded through SBIR grants towards the development of a promising diagnosis instrument for exploration missions. rHEALTH ONE is the interim version of the technology, functional as a benchtop analyzer and test bed for the next generation of rHEALTH in development. Several modifications were made to the rHEALTH ONE analyzer for operation in microgravity. For function, fluid management was key. A sheath-based analyzer uses sheath fluid to flow the sample, cleaning fluid to prevent biological contamination, and a reservoir to collect the liquid waste. The rHEALTH ONE analyzer uses bottles dependent on gravity to separate the air and liquid pathways and keep the liquids contained. It uses only 1 psig of air pressure to directly push the liquid through the device, requiring little-to-no resistance at inlet and outlet. A microtubing assembly with self-sealing luer connectors was designed – featuring 0.014 mm thick durable medical balloons to hold water inside the supply bottles – to create safe containment and easy access for the crew while maintaining the analyzer’s function. For safety, copper tape was added to the interior of the plastic housing to reduce electromagnetic interference, fluid and electrical connections were secured against vibration and leaks, and gaps were further sealed to ensure containment of the optical block and lasers. Water as the sheath and cleaning fluid and TOX 0 samples were used to reduce the biohazard risk to the crew. In May 2022, European Space Agency astronaut Samantha Cristoforetti demonstrated the rHEALTH ONE aboard ISS for its sample loading, flow cytometry, and data collection capability in microgravity. The JSC Immunology Lab provided flow cytometry expertise, designed the sample test protocol, and manufactured and benchmarked the flight samples on a ‘gold-standard’ flow cytometer. The analyzer was primed with water, purged of air, and four calibration solutions of polystyrene microparticles were tested to characterize its performance. Tightly controlled procedures and excellent execution prevented air bubble interference during air/water separation, fluid transfer, sample mixing and loading. Data showed a slight increase in signal noise on 3 of 5 channels and an anomaly of fluorophores migrating in one sample (confirmed by JSC post-flight). Flight results correctly detected the change in sample, matched the analyzer’s ground performance, and were consistent with the gold-standard’s ground results. Although areas were noted for improvement, these outcomes signified complete mission success.

R. S. Miller↗
DOE OSTI2022

Light-Driven Charge Transport and Optical Sensing in Molecular Junctions

Probing charge and energy transport in molecular junctions (MJs) has not only enabled a fundamental understanding of quantum transport at the atomic and molecular scale, but it also holds significant promise for the development of molecular-scale electronic devices. Recent years have witnessed a rapidly growing interest in understanding light-matter interactions in illuminated MJs. These studies have profoundly deepened our knowledge of the structure–property relations of various molecular materials and paved critical pathways towards utilizing single molecules in future optoelectronics applications. In this article, we survey recent progress in investigating light-driven charge transport in MJs, including junctions composed of a single molecule and self-assembled monolayers (SAMs) of molecules, and new opportunities in optical sensing at the single-molecule level. We focus our attention on describing the experimental design, key phenomena, and the underlying mechanisms. Specifically, topics presented include light-assisted charge transport, photoswitch, and photoemission in MJs. Emerging Raman sensing in MJs is also discussed. Finally, outstanding challenges are explored, and future perspectives in the field are provided.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Data from: A high-quality genome assembly of the tetraploid Teucrium chamaedrys unveils a recent whole genome duplication and a large biosynthetic gene cluster for diterpenoid metabolism

Teucrium is well known for making clerodane-type diterpenoids that are produced from the backbone kolavanyl diphosphate. In order to begin to elucidate some of the complex biosynthetic pathways of these medicinal compounds, we identified and functionally characterized several kolavanyl diphosphate synthases from T. chamaedrys . Along the way, we discovered the genome of this species to be one of the largest genomes published from the Lamiaceae family, to which it belongs. This tetraploid, 3 Gbp genome is especially rich in diterpene synthase genes, with 74 putative sequences identified.

biosynthetic gene cluster (BGC)↗
NASA NTRS1998

The molecular basis of ethylene signalling in Arabidopsis

The simple gas ethylene profoundly influences plants at nearly every stage of growth and development. In the past ten years, the use of a genetic approach, based on the triple response phenotype, has been a powerful tool for investigating the molecular events that underlie these effects. Several fundamental elements of the pathway have been described: a receptor with homology to bacterial two-component histidine kinases (ETR1), elements of a MAP kinase cascade (CTR1) and a putative transcription factor (EIN3). Taken together, these elements can be assembled into a simple, linear model for ethylene signalling that accounts for most of the well-characterized ethylene mediated responses.

Non-NASA Center↗
DOE OSTI2021

Electrolysis on a Chip with Tunable Thin Film Nanostructured PGM Electrocatalysts Generated from Self-Assembled Block Copolymer Templates

Self-assembled block copolymers are promising templates for fabricating thin film materials with tuned periodic feature sizes and geometry at the nanoscale. Here, a series of nanostructured platinum and iridium oxide electrocatalysts templated from poly(styrene)-block-poly(vinyl pyridine) (PSbPVP) block copolymers via an incipient wetness impregnation (IWI) pathway is reported. Both nanowire and nanocylinder electrocatalysts of varying feature sizes are assessed and higher catalyst loadings are achieved by the alkylation of the pyridine moieties in the PVP block prior to IWI. Electrocatalyst evaluations featuring hydrogen pump and water electrolysis demonstrations are carried out on interdigitated electrode (IDE) chips flexible with liquid supporting electrolytes and thin film polymer electrolytes. Notably, the mass activities of the nanostructured electrocatalysts from alkylated block copolymer templates are 35%–94% higher than electrocatalysts from non-alkylated block copolymer templates. Standing cylinder nanostructures lead to higher mass activities than lamellar variants despite their not having the largest surface area per unit catalyst loading demonstrating that mesostructure architectures have a profound impact on reactivity. Overall, IDE chips with model thin film electrocatalysts prepared from self-assembled block copolymers offer a high-throughput experimental method for correlating electrocatalyst nanostructure and composition to electrochemical reactivity.

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

Operating High-Energy Lithium-Metal Pouch Cells with Reduced Stack Pressure Through a Rational Lithium-Host Design

Transitioning from a liquid electrolyte to an inorganic solid electrolyte offers a potential pathway to enable highly reversible lithium-metal anodes. However, the solid-electrolyte-protected lithium-metal anode suffers from poor interfacial ionic contacts and requires an impractically high stack pressure (>1.0 MPa) to maintain the interfacial contacts. It is demonstrated here that combining a hollow silver/carbon fiber scaffold and an inorganic/organic composite electrolyte enables a highly reversible lithium-metal anode. Since the high surface area of the electrode provides intimate contact and the hollow structure of the electrode relieves the lithium plating-induced stress, the electrode/electrolyte interface remains stable during cycling even under mild stack pressure. This unconventional structural design is validated in practical pouch cells assembled with the 3D lithium host containing a onefold excess of lithium and a high-nickel cathode. At a mild stack pressure of 320 kPa, the pouch cell displays 83% capacity retention for 200 cycles. This work illustrates that combining a hollow electrode architecture and a robust solid electrolyte offers a practical pathway toward rechargeable lithium-metal anodes.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Interfacial Assembly and Jamming of Polyelectrolyte Surfactants: A Simple Route To Print Liquids in Low-Viscosity Solution

Nanoparticle surfactants (NPSs) assembled at the oil-water interface can significantly lower the interfacial tension and be used to structure liquids. However, to realize the three-dimensional printing of one liquid in another, high-viscosity liquids, for example, silicone oil, have been generally used. In this work, we present a simple, low-cost approach to print water in low-viscosity toluene by using a new type of polyelectrolyte surfactant, sodium carboxymethyl cellulose surfactant (CMCS), that forms and assembles at the oil-water interface. The interfacial activity of CMCSs can be enhanced by tuning parameters, such as pH and concentration, and the incorporation of a rigid ligand affords excellent mechanical strength to the resultant assemblies. With CMCS jammed at the interface, liquids can be easily printed or molded to the desired shapes, with biocompatible walls that can be used to encapsulate and adsorb active materials. This study opens a new pathway to generate complex, all-liquid devices with a myriad of potential applications in biology, catalysis, and chemical separation.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Evaluating the Effects of Anode Porous Transport Layer on the Performance and Durability of Anion Exchange Membrane Electrolyzers

As anion exchange membrane systems have emerged as a competitive low temperature electrolysis technology, research has expanded to other components and device integration. In this study, nickel (Ni) and stainless steel (SS)-based porous transport layers (PTLs) are investigated in membrane electrode assemblies (MEAs). Compared to MEAs using Ni, the SS PTL shows higher performance due to less kinetics and residual loss and possibly due to a combination of iron mobility improving oxygen evolution reactivity and electron conduction pathways, as well as higher porosity increasing site access. Voltage decay rates of approximately 144 and 115 μV/h, respectively, for the Ni and SS PTLs are found, although the long-term durability and lifetime implications are convoluted. Voltage breakdown analysis confirms that both PTLs saw significant increases in residual loss possibly due to catalyst/PTL property changes that affected electronic, ionic, and mass transport pathways. For the Ni PTL, a higher proportion of the losses were due to cell kinetics; comparatively, more of the SS PTL losses were due to increases in the high frequency resistance. The experimental findings presented here provide insights on the impact of the PTL materials and their properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

An Updated Analysis of Clad Degradation

This report provides an analysis of the clad barrier function associated with the direct disposal of dual purpose canisters (DPCs) under hypothetical conditions in a shale repository and in an alluvial repository, including the effect of a postulated criticality event inside a disposed DPC. Should a postulated criticality event occur in a hypothetical shale repository, cladding will primarily degrade by general corrosion. Stress corrosion cracking, hydride cracking, creep failure, pitting and crevice corrosion, rod pressurization, and clad unzipping are calculated to have little impact on cladding persistence. At the higher temperature expected during a postulated criticality event in a saturated shale repository, general corrosion of cladding would be rapid - on the order of 0.034 microns/yr. A few hundred years after onset of a postulated criticality event in a shale repository complete general corrosion of fuel assembly grid spacer walls and guide tubes will likely result in settling of fuel rods upon each other. This rod consolidation should displace the water moderator and possibly terminate a postulated criticality. The primary potential degradation pathway for cladding in a hypothetical alluvial repository is localized corrosion by fluoride, which cannot occur in a shale repository. Fluoride-enhanced corrosion of cladding would be accelerated under the slightly higher (< 100°C) temperatures associated with a postulated criticality event. The impact of criticality in both cases (shale and alluvial) would be to increase the amount of failed cladding. But it would require very specialized transport pathways.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2022

Evolutionary Divergence of Marinobacter Strains in Cryopeg Brines as Revealed by Pangenomics

Marinobacter spp. are cosmopolitan in saline environments, displaying a diverse set of metabolisms that allow them to competitively occupy these environments, some of which can be extreme in both salinity and temperature. Here, we introduce a distinct cluster of Marinobacter genomes, composed of novel isolates and in silico assembled genomes obtained from subzero, hypersaline cryopeg brines, relic seawater-derived liquid habitats within permafrost sampled near Utqiaġvik, Alaska. Using these new genomes and 45 representative publicly available genomes of Marinobacter spp. from other settings, we assembled a pangenome to examine how the new extremophile members fit evolutionarily and ecologically, based on genetic potential and environmental source. This first genus-wide genomic analysis revealed that Marinobacter spp. in general encode metabolic pathways that are thermodynamically favored at low temperature, cover a broad range of organic compounds, and optimize protein usage, e.g., the Entner–Doudoroff pathway, the glyoxylate shunt, and amino acid metabolism. The new isolates contributed to a distinct clade of subzero brine-dwelling Marinobacter spp. that diverged genotypically and phylogenetically from all other Marinobacter members. The subzero brine clade displays genomic characteristics that may explain competitive adaptations to the extreme environments they inhabit, including more abundant membrane transport systems (e.g., for organic substrates, compatible solutes, and ions) and stress-induced transcriptional regulatory mechanisms (e.g., for cold and salt stress) than in the other Marinobacter clades. We also identified more abundant signatures of potential horizontal transfer of genes involved in transcription, the mobilome, and a variety of metabolite exchange systems, which led to considering the importance of this evolutionary mechanism in an extreme environment where adaptation via vertical evolution is physiologically rate limited. Assessing these new extremophile genomes in a pangenomic context has provided a unique view into the ecological and evolutionary history of the genus Marinobacter , particularly with regard to its remarkable diversity and its opportunism in extremely cold and saline environments.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1998

Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach

Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.

Srivastava, Deepak↗