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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 847 records · Page 47
All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Sub-Eddington Supermassive Black Hole Activity in Fornax Early-type Galaxies

We characterize the incidence and intensity of low-level supermassive black hole activity within the Fornax cluster, through X-ray observations of the nuclei of 29 quiescent early-type galaxies. Using the Chandra X-ray Telescope, we target 17 galaxies from the Hubble Space Telescope Fornax Cluster Survey, down to a uniform (3σ) limiting X-ray luminosity threshold of 5 x 10^(38) erg/s, which we combine with deeper, archival observations for an additional 12 galaxies. A nuclear X-ray point source is detected in 11 out of 29 targets. After accounting for the low-mass X-ray binary contamination to the nuclear X-ray signal, the X-ray active fraction is measured at 26.6% ± 9.6%. The results from this analysis are compared to similar investigations targeting quiescent early types in the Virgo cluster, as well as the field. After correcting for the different mass distributions, the measured Fornax active fraction is less than the field fraction, at more than 3σ, confirming that the funneling of gas to the nuclear regions of cluster members is inhibited compared to those galaxies in the field. At the same time, we find no statistically significant difference between Fornax and Virgo galaxies, with only marginal evidence for a lower active fraction in Fornax (1σ); if real, owing to Fornaxʼs higher galaxy number density, this could indicate that galaxy–galaxy interactions are more effective at gas removal than galaxy-gas effects.

Nathan Lee↗
DOE OSTI2023

Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer

ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7. Here, we present cryo-EM structures of human Uba7 in complex with UBE2L6, ISG15 adenylate, and ISG15 thioester intermediate that are poised for catalysis of Uba7-UBE2L6-ISG15 thioester transfer. Our structures reveal a unique overall architecture of the complex compared to structures from the ubiquitin conjugation pathway, particularly with respect to the location of ISG15 thioester intermediate. Our structures also illuminate the molecular basis for Uba7 activities and for its exquisite specificity for ISG15 and UBE2L6. Altogether, our structural, biochemical, and human cell-based data provide significant insights into the functions of Uba7, UBE2L6, and ISG15 in cells.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2016

Global Energetics of Solar Flares: Nonthermal Energies - Part III

This study entails the third part of a global flare energetics project, in which Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) data of 191 M and X-class flare events from the first 3.5 years of the Solar Dynamics Observatory mission are analyzed. We fit a thermal and a nonthermal component to RHESSI spectra, yielding the temperature of the differential emission measure (DEM) tail, the nonthermal power-law slope and flux, and the thermal nonthermal cross-over energy eco. From these parameters, we calculate the total nonthermal energy E(sub nt) in electrons with two different methods: (1) using the observed cross-over energy e(sub co) as low-energy cutoff, and (2) using the low-energy cut off e(sub wt) predicted by the warm thick-target bremsstrahlung model of Kontar et al. Based on a mean temperature of T(sub e) = 8.6 MK in active regions, we find low-energy cutoff energies of e(sub wt) = 6.2 +/-1.6 keV for the warm-target model, which is significantly lower than the cross-over energies e(sub co) = 21 +/- 6 keV. Comparing with the statistics of magnetically dissipated energies E(sub mag) and thermal energies E(sub th) from the two previous studies, we find the following mean (logarithmic) energy ratios with the warm-target model: E(sub nt) = 0.41E(sub mag), E(sub th) = 0.08 E(sub mag), and E(sub th) = 0.15 E(sub nt). The total dissipated magnetic energy exceeds the thermal energy in 95% and the nonthermal energy in 71% of the flare events, which confirms that magnetic reconnection processes are sufficient to explain flare energies. The nonthermal energy exceeds the thermal energy in 85% of the events, which largely confirms the warm thick-target model.

Aschwanden, Markus J.↗
DOE OSTI2022

Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD

Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT 2A serotonin receptor (HTR2A), the 5-HT 2B serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. Here, in this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD’s action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2020

Autonomous Navigation over Europa Analogue Terrain for an Actively Articulated Wheel-on-Limb Rover

The ocean world Europa is a prime target forexploration given its potential habitability [1]. We proposea mobile robotic system that is capable of autonomouslytraversing hundreds of meters to visit multiple sites of intereston a Europan analogue surface. Due to the topology of Europanterrain being largely unknown, it is desired that this mobilitysystem traverse a large variety of terrain types. The mobilitysystem should also be capable of crossing unstructured terrainin an autonomous manner given the communications limitationsbetween Earth and Europa.A wheel-on-limb robotic rover is presented that may activelyconform to terrain features up to 1.5 wheel diameters tall whiledriving. The robot uses a sampling-based motion planner togenerate paths that leverage its unique locomotive capabilities.The planner assesses terrain hazards and wheel workspacelimits as obstacles. It may also select a mobility mode basedon predicted energy usage and the need for limb articulationon the terrain being traversed. This autonomous mobility wasevaluated on the chaotic salt-evaporite terrain found in DeathValley, CA, an analogue to the Europan surface. Over the courseof 38 trials, the rover autonomously traversed 435m of extremeterrain while maintaining a rate of 0.64 traverse ending failuresfor every 10m driven.

Meirion-Griffith, Gareth↗
DOE OSTI2022

Development of a Lateral Flow Strip-Based Recombinase-Aided Amplification for Active Chlamydia psittaci Infection

Chlamydia psittaci is the causative agent of psittacosis, a worldwide zoonotic disease. A rapid, specific, and sensitive diagnostic assay would be benefit for C. psittaci infection control. In this study, an assay combining recombinase-aided amplification and a lateral flow strip (RAA-LF) for the detection of active C. psittaci infection was developed. The RAA-LF assay targeted the CPSIT_RS02830 gene of C. psittaci and could be accomplished in 15 min at a single temperature (39°C). The analytical sensitivity of the assay was as low as 1 × 10 0 copies/μl and no cross-reaction with some other intracellular pathogens was observed. Moreover, all feces samples from mice infected with C. psittaci at day-1 post-infection were positive in the RAA-LF assay. In conclusion, the RAA-LF assay provides a convenient, rapid, specific and sensitive method for detection of active C. psittaci infection and it is also suitable for C. psittaci detection in field.

Jiao, Jun↗
DOE OSTI2024

Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection

ABSTRACT Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step inde novoguanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whetherin vivoinhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacyin vivoagainstAcinetobacter baumanniimouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures ofA. baumannii, Staphylococcus aureus, andEscherichia coliGuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clearin vivoefficacy of these small molecule GuaB inhibitors in a model ofA. baumanniiinfection validates GuaB as an essential antibiotic target. IMPORTANCE The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition ofde novoguanine biosynthesis is bactericidal in a mouse model ofAcinetobacter baumanniiinfection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

Microbiology↗
DOE OSTI2022

Gems of the Galaxy Zoos—A Wide-ranging Hubble Space Telescope Gap-filler Program*

We describe the Gems of the Galaxy Zoos (Zoo Gems) project, a gap-filler project using short windows in the Hubble Space Telescope's schedule. As with previous snapshot programs, targets are taken from a pool based on position; we combine objects selected by volunteers in both the Galaxy Zoo and Radio Galaxy Zoo citizen-science projects. Zoo Gems uses exposures with the Advanced Camera for Surveys to address a broad range of topics in galaxy morphology, interstellar-medium content, host galaxies of active galactic nuclei, and galaxy evolution. Science cases include studying galaxy interactions, backlit dust in galaxies, post-starburst systems, rings and peculiar spiral patterns, outliers from the usual color–morphology relation, Green Pea compact starburst systems, double radio sources with spiral host galaxies, and extended emission-line regions around active galactic nuclei. For many of these science categories, final selection of targets from a larger list used public input via a voting process. Highlights to date include the prevalence of tightly wound spiral structure in blue, apparently early-type galaxies, a nearly complete Einstein ring from a group lens, redder components at lower surface brightness surrounding compact Green Pea starbursts, and high-probability examples of spiral galaxies hosting large double radio sources.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2026

Data for Expression of a Bacterial Trehalose 6-Phosphate Synthase Gene otsA in Camelina sativa Seeds Promotes the Channelling of Carbon Towards Oil Accumulation

Improving seed oil yield is essential for developing Camelina sativa as a sustainable biofuel crop. Fatty acid synthesis depends on the production of acetyl-CoA from photosynthetically derived sugars. Trehalose 6-phosphate (T6P), a proxy for sucrose availability, can link sugar status to plant growth and development. Synthesised by trehalose 6-phosphate synthase (TPS) from UDP-glucose and glucose-6-phosphate, T6P plays a regulatory role in metabolism. Our previous studies on Arabidopsis transgenic lines constitutively expressing the E. coli otsA (encoding TPS) showed increased T6P levels and seed triacylglycerol, along with stunted growth. In the present study we express otsA in camelina under the control of a seed-specific Phaseolin promoter. Seeds of the resulting transgenic lines accumulated high levels of T6P, and a 15%–20% increase in total fatty acids and triacylglycerol compared to wild-type. Molecular analysis showed the transgenic seeds had reduced SnRK1 activity, elevated WRI1 protein levels, and increased the levels of WRI1 and its target genes, along with enhanced rates of fatty acid synthesis that increased seed weights relative to wild type. Notably, the increase in oil did not affect seed protein levels but did reduce the soluble metabolite fraction. Crucially, seed-specific expression of otsA mitigated the growth defects associated with constitutive otsA expression, and the transgenic lines showed normal seed development and germination. These findings demonstrate that targeted T6P modulation via seed-specific otsA expression is an effective metabolic engineering strategy to boost oil production in camelina and potentially in other oilseed crops and bioenergy crops such as energycane, sorghum and miscanthus.

Lipids↗
DOE OSTI2022

Triplet Photosensitized para -Hydrogen Induced Polarization

Despite its enormous utility in structural characterization, nuclear magnetic resonance (NMR) spectroscopy is inherently limited by low spin polarization. One method to address the low polarization is para-hydrogen (p-H 2 ) induced polarization (PHIP) which uses the singlet spin isomer of H 2 to generate disparate nuclear spin populations to amplify the associated NMR signals. PHIP often relies on thermal catalysis or, more infrequently, UV-activated catalytic hydrogenation. Light-activated hydrogenation enables direct and timed control over the hyperpolarization of target substrates, critical for identifying short-lived intermediates. Here, we use an established Ir(III) triplet photosensitizer (PS) to visible light sensitize the triplet ligand-field states in the d6-transition metal dihydride Ru(CO)(PPh 3 ) 3 (H) 2 (1). Excitation inside a 9.4 T NMR spectrometer with the PS and a 420 nm blue LED, under 3 atm of p-H 2 , successfully photosensitized hyperpolarization in 1 and in a range of unsaturated substrates at and below room temperature, up to 1630-fold. In otherwise identical experimental conditions without light activation, no polarization was realized in 1 or the substrates evaluated. We believe triplet-sensitized PHIP (Trip- PHIP) represents a facile experimental means for probing triplet sensitized light activation in transition metal catalysts possessing low-lying triplet ligand-field states, providing mechanistic insight of potentially tremendous value in chemical catalysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Natural diversity screening, assay development, and characterization of nylon-6 enzymatic depolymerization

Successes in biocatalytic polyester recycling have raised the possibility of deconstructing alternative polymers enzymatically, with polyamide (PA) being a logical target due to the array of amide-cleaving enzymes present in nature. Here, we screen 40 potential natural and engineered nylon-hydrolyzing enzymes (nylonases), using mass spectrometry to quantify eight compounds resulting from enzymatic nylon-6 (PA6) hydrolysis. Comparative time-course reactions incubated at 40-70 °C showcase enzyme-dependent variations in product distributions and extent of PA6 film depolymerization, with significant nylon deconstruction activity appearing rare. The most active nylonase, a NylC K variant we rationally thermostabilized (an N-terminal nucleophile (Ntn) hydrolase, NylC K -TS, T m = 87.4 °C, 16.4 °C higher than the wild-type), hydrolyzes 0.67 wt% of a PA6 film. Reactions fail to restart after fresh enzyme addition, indicating that substrate-based limitations, such as restricted enzyme access to hydrolysable bonds, prohibit more extensive deconstruction. Overall, this study expands our understanding of nylonase activity distribution, indicates that Ntn hydrolases may have the greatest potential for further development, and identifies key targets for progressing PA6 enzymatic depolymerization, including improving enzyme activity, product selectivity, and enhancing polymer accessibility.

09 BIOMASS FUELS↗
DOE OSTI2024

Predicting transcription factor activity using prior biological information

Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2003

Investigation of Neural Strategies of Visual Search

The goal of this project was to measure how neurons in the superior colliculus (SC) change their activity during a visual search task. Specifically, we proposed to measure how the activity of these neurons was altered by the discriminability of visual targets and to test how these changes might predict the changes in the subjects performance. The primary rationale for this study was that understanding how the information encoded by these neurons constrains overall search performance would foster the development of better models of human performance. Work performed during the period supported by this grant has achieved these aims. First, we have recorded from neurons in the superior colliculus (SC) during a visual search task in which the difficulty of the task and the performance of the subject was systematically varied. The results from these single-neuron physiology experiments shows that prior to eye movement onset, the difference in activity across the ensemble of neurons reaches a fixed threshold value, reflecting the operation of a winner-take-all mechanism. Second, we have developed a model of eye movement decisions based on the principle of winner-take-all . The model incorporates the idea that the overt saccade choice reflects only one of the multiple saccades prepared during visual discrimination, consistent with our physiological data. The value of the model is that, unlike previous models, it is able to account for both the latency and the percent correct of saccade choices.

Krauzlis, Richard J.↗
DOE OSTI2026

Bemnifosbuvir: An HCV NS5B Inhibitor With Multiple Modes of Action

Bemnifosbuvir (BEM) is a potent, pan-genotypic inhibitor targeting the hepatitis C virus (HCV) NS5B polymerase. Its antiviral activity was evaluated in an ascending dose phase I clinical trial involving 30 patients treated once a day for 7 days. After treatment initiation, plasma HCV RNA declined in a biphasic manner with a mean reduction of 2.3 log 10 IU/mL after 24 hours and 4.4 log10 IU/mL by day 7 for the highest dose. Alanine aminotransferase (ALT) also normalized in most patients. We employed a multiscale mathematical model fitted to the HCV RNA and ALT dynamics to quantify the antiviral activity and evaluate the modes of action of BEM. We found that models in which BEM only acted as a typical HCV RNA polymerase inhibitor and reduced the intracellular production of HCV RNA did not fit the data as well as models in which BEM had multiple modes of action, including suppressing viral assembly and secretion and enhancing intracellular HCV RNA degradation. BEM's effectiveness in inhibiting intracellular HCV RNA production increased with dose (150 mg/day: 88.2%, 300 mg/day: 98.8%, 600 mg/day: 99.5%), while inhibition of viral assembly and release was ~95% effective regardless of dose. We observed a dose-dependent enhancement in the degradation of intracellular HCV RNA, with degradation rates 1.5-fold higher in patients receiving 300 mg/day and 2.7-fold higher in those receiving 600 mg/day than in patients receiving 150 mg/day. No significant differences in antiviral activity were detected between HCV genotypes 1b and 3 or between patients with and without compensated cirrhosis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9

Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels. Cryoelectron microscopy (cryo-EM) structures of the wild-type and improved GeoCas9 (iGeoCas9) enzymes reveal extended contacts between the WED domain of iGeoCas9 and DNA substrates. Biochemical analysis shows that iGeoCas9 accelerates DNA unwinding to capture substrates under the magnesium-restricted conditions typical of mammalian but not bacterial cells. These findings enabled rational engineering of other Cas9 orthologs to enhance genome-editing levels, pointing to a general strategy for editing enzyme improvement. Together, these results uncover a new role for the Cas9 WED domain in DNA unwinding and demonstrate how accelerated target unwinding dramatically improves Cas9-induced genome-editing activity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1–D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Real-time monitoring of the orthohydrogen fraction in a liquid hydrogen moderator

Here, we present the first direct measurements of the orthohydrogen fraction in an operating liquid hydrogen moderator loop at a high-powered neutron source. We have developed a Raman immersion probe capable of characterizing the orthohydrogen and parahydrogen makeup of a liquid hydrogen loop approximately every ten seconds, which can see orthohydrogen fractions lower than 0.20 without difficulty. At the Spallation Neutron Source, where the time-averaged power deposition in the studied moderator system is around 0.02 W/cm 3 , the orthohydrogen fraction increases with beam power and equilibrates at levels of 0.40 and responds to beam trips in a dynamic fashion. Additionally, we find that without deliberate catalyst systems in place, the relaxation due to the piping in the system has insignificant effect in catalyzing the relaxation of freshly condensed hydrogen toward thermodynamic equilibrium, and that the radiation levels associated with activation in a non-operating spallation neutron source target-moderator-reflector assembly likewise has insignificant effect on the liquid hydrogen kinetics.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2021

Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors

Dopamine controls diverse behaviors and their dysregulation contributes to many disorders. Our ability to understand and manipulate the function of dopamine is limited by the heterogenous nature of dopaminergic projections, the diversity of neurons that are regulated by dopamine, the varying distribution of the five dopamine receptors (DARs), and the complex dynamics of dopamine release. In order to improve our ability to specifically modulate distinct DARs, here we develop a photo-pharmacological strategy using a Membrane anchored Photoswitchable orthogonal remotely tethered agonist for the Dopamine receptor (MP-D). Our design selectively targets D1R/D5R receptor subtypes, most potently D1R (MP-D1 ago ), as shown in HEK293T cells. In vivo, we targeted dorsal striatal medium spiny neurons where the photo-activation of MP-D1 ago increased movement initiation, although further work is required to assess the effects of MP-D1 ago on neuronal function. Our method combines ligand and cell type-specificity with temporally precise and reversible activation of D1R to control specific aspects of movement. Our results provide a template for analyzing dopamine receptors.

59 BASIC BIOLOGICAL SCIENCES↗