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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 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

PMN inhibits colorectal cancer cells through inducing mitotic arrest and p53-dependent apoptosis via the inhibition of tubulin polymerization

Highlights: • PMN inhibits CRC cell proliferation through inducing mitotic arrest and apoptosis. • PMN induces mitotic arrest via the inhibition of microtubule polymerization. • PMN-induced mitotic arrest results in apoptosis and p53 upregulation. • PMN-induced apoptosis is partially mediated by p53. Colorectal cancer (CRC) is the third most prevalent malignancy worldwide. New understandings about this disease are urgently required to guide clinical therapies. In this study, we focused on the effects of the small molecule PMN on CRC cells. PMN dose-dependently inhibited CRC cell proliferation through inducing mitotic arrest and apoptosis. PMN induced mitotic arrest via the disruption of spindle apparatus by inhibiting microtubule polymerization. PMN-induced mitotic arrest resulted in apoptosis and p53 upregulation. Furthermore, p53 upregulation sensitized PMN-induced mitotic cells to apoptosis. This study deepens the understanding of the effects of p53 on the response of CRC cells to PMN, providing the basis for the potential development of PMN as a lead compound of microtubule-destabilizers for p53-positive CRC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Crystal structure of a thermophilic O 6-alkylguanine-DNA alkyltransferase-derived self-labeling protein-tag in covalent complex with a fluorescent probe

Highlights: • The labeling of proteins is a valid approach for studying their function. • SNAP-tag{sup ®} is a self-labeling protein tag that binds different probes (e.g. SVG). • SsOGT-H{sup 5} is a thermostable alternative to the SNAP-tag{sup ®} technology. • The SsOGT-H{sup 5}-SVG structure reveals new details of protein-probe interaction. • The SsOGT-H{sup 5}-SVG structure highlights new OGTs structure-function relationships. The self-labeling protein tags are robust and versatile tools for studying different molecular aspects of cell biology. In order to be suitable for a wide spectrum of experimental conditions, it is mandatory that these systems are stable after the fluorescent labeling reaction and do not alter the properties of the fusion partner. SsOGT-H{sup 5} is an engineered variant alkylguanine-DNA-alkyl-transferase (OGT) of the hyperthermophilic archaeon Sulfolobus solfataricus, and it represents an alternative solution to the SNAP-tag{sup ®} technology under harsh reaction conditions. Here we present the crystal structure of SsOGT-H{sup 5} in complex with the fluorescent probe SNAP-Vista Green{sup ®} (SsOGT-H{sup 5}-SVG) that reveals the conformation adopted by the protein upon the trans-alkylation reaction with the substrate, which is observed covalently bound to the catalytic cysteine residue. Moreover, we identify the amino acids that contribute to both the overall protein stability in the post-reaction state and the coordination of the fluorescent moiety stretching-out from the protein active site. We gained new insights in the conformational changes possibly occurring to the OGT proteins upon reaction with modified guanine base bearing bulky adducts; indeed, our structural analysis reveals an unprecedented conformation of the active site loop that is likely to trigger protein destabilization and consequent degradation. Interestingly, the SVG moiety plays a key role in restoring the interaction between the N- and C-terminal domains of the protein that is lost following the new conformation adopted by the active site loop in the SsOGT-H{sup 5}-SVG structure. Molecular dynamics simulations provide further information into the dynamics of SsOGT-H{sup 5}-SVG structure, highlighting the role of the fluorescent ligand in keeping the protein stable after the trans-alkylation reaction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The C-terminus of Ubl4A is critical for pro-death activity and association with the Arp2/3 complex

Highlights: • The Ubl4A C-terminus has a pro-death function. • Ubl4A interacts with the Arp2/3 complex through its C-terminus. • A single mutation in Ubl4A C-terminus abolishes its association with Arp2/3. • The D122A mutation also diminishes Ubl4A cytotoxicity in cancer cells. Ubl4A is a small ubiquitin-like protein involved in diverse cellular functions. We have shown that Ubl4A is critical for survival of the starvation-mediated cell death in vivo. The underlying mechanism for this is through interaction with the actin-related protein Arp2/3 complex and promotion of actin branching. Interestingly, “put-back” of Ubl4A to Ubl4A-deficient cells also results in cell death. Removal of the Ubl4A N-terminus significantly enhances its cytotoxicity, indicating that the pro-death activity of Ubl4A is mainly from its C-terminal region. In vitro protein pull-down assays show that the C-terminal region of Ubl4A can directly interact with the Arp2/3 complex. The single point mutation of an aspartic acid to alanine (D122A) in the Ubl4A C-terminus abolishes its ability to bind the Arp2/3 complex. This mutation also destabilizes Ubl4A proteins susceptible to protease degradation. Importantly, ectopic expression of wild-type Ubl4A can induce cell death in colon cancer cells, but such pro-death activity is diminished in the D122A mutant. These data suggest that Ubl4A C-terminus, especially D122, is critical for Ubl4A-Arp2/3 interaction and its pro-death function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Feedstock and Catalyst Impact on Bio-Oil Production and FCC Co-Processing to Fuels

NREL's thermochemical biomass conversion research is focused on ex-situ upgrading of biomass fast-pyrolysis (FP) vapors as an efficient route to completely biogenic pyrolysis-based fuel precursors, fuels, and value-added chemicals depending on catalyst and process conditions. A near term pathway being developed uses these liquids for co-processing with petroleum feedstocks to assess biogenic carbon incorporation in hydrocarbon fuel feedstocks for potential refinery use. In this work, the impact of feedstock and catalyst on catalytic fast pyrolysis oil (CFPO) composition was determined with the oils then assessed for biogenic fuel production via FCC (fluidized catalytic cracking) co-processing. Biomass vapors were generated via fast pyrolysis with destabilizing vapor components (char, inorganics, tar aerosols) removed by hot gas filtration to produce clean vapors more responsive to catalytic upgrading. A Davison Circulating Riser (DCR), a petroleum industry standard for fluidized catalytic cracking (FCC) catalyst evaluation, was coupled to a custom pyrolyzer system designed to produce consistent-composition pyrolysis vapors as feed to the DCR. Pyrolysis vapors, derived from pure hardwood and softwood, were upgraded using commercially available modified zeolite-based catalysts to produce CFPOs. These upgraded oils were analyzed via 31P and 13C NMR spectroscopy, GCxGC-TOF/MS, carbonyl and ultimate analysis (CHNO), and simulated distillation (SIMDIS) to assess both oil chemistry and distillation behavior as they relate to catalyst and feedstock type for producing fungible hydrocarbon product liquids. These exploratory vapor-phase-upgrading results demonstrated the feasibility of producing refinery-compatible hydrocarbon fuel intermediates entirely from biomass-derived fast-pyrolysis vapors using an industry-accepted DCR system for catalytic upgrading. The FCC co-processing results demonstrated the feasibility of using CFPOs with VGO feeds in FCC refinery operations to produce biogenic carbon containing fuels.

biogenic carbon↗
DOE OSTI2011

Design Function and Structure of a Monomeric CLC Transporter

Channels and transporters of the ClC family cause the transmembrane movement of inorganic anions in service of a variety of biological tasks, from the unusual - the generation of the kilowatt pulses with which electric fish stun their prey - to the quotidian - the acidification of endosomes, vacuoles and lysosomes. The homodimeric architecture of ClC proteins, initially inferred from single-molecule studies of an elasmobranch Cl{sup -} channel and later confirmed by crystal structures of bacterial Cl{sup -}/H{sup +} antiporters, is apparently universal. Moreover, the basic machinery that enables ion movement through these proteins - the aqueous pores for anion diffusion in the channels and the ion-coupling chambers that coordinate Cl{sup -} and H{sup +} antiport in the transporters - are contained wholly within each subunit of the homodimer. The near-normal function of a bacterial ClC transporter straitjacketed by covalent crosslinks across the dimer interface and the behaviour of a concatemeric human homologue argue that the transport cycle resides within each subunit and does not require rigid-body rearrangements between subunits. However, this evidence is only inferential, and because examples are known in which quaternary rearrangements of extramembrane ClC domains that contribute to dimerization modulate transport activity, we cannot declare as definitive a 'parallel-pathways picture in which the homodimer consists of two single-subunit transporters operating independently. A strong prediction of such a view is that it should in principle be possible to obtain a monomeric ClC. Here we exploit the known structure of a ClC Cl{sup -}/H{sup +} exchanger, ClC-ec1 from Escherichia coli, to design mutants that destabilize the dimer interface while preserving both the structure and the transport function of individual subunits. The results demonstrate that the ClC subunit alone is the basic functional unit for transport and that cross-subunit interaction is not required for Cl{sup -}/H{sup +} exchange in ClC transporters.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

The role of histone tails in the nucleosome: A computational study

Histone tails play an important role in gene transcription and expression. We present here a systematic computational study of the role of histone tails in the nucleosome, using replica exchange molecular dynamics simulations with an implicit solvent model and different well-established force fields. We performed simulations for all four histone tails, H4, H3, H2A, and H2B, isolated and with inclusion of the nucleosome. The results confirm predictions of previous theoretical studies for the secondary structure of the isolated tails but show a strong dependence on the force field used. In the presence of the entire nucleosome for all force fields, the secondary structure of the histone tails is destabilized. Specific contacts are found between charged lysine and arginine residues and DNA phosphate groups and other binding sites in the minor and major DNA grooves. Using cluster analysis, we found a single dominant configuration of binding to DNA for the H4 and H2A histone tails, whereas H3 and H2B show multiple binding configurations with an equal probability. The leading stabilizing contribution for those binding configurations is the attractive interaction between the positively charged lysine and arginine residues and the negatively charged phosphate groups, and thus the resulting charge neutralization. Lastly, we present results of molecular dynamics simulations in explicit solvent to confirm our conclusions. Results from both implicit and explicit solvent models show that large portions of the histone tails are not bound to DNA, supporting the complex role of these tails in gene transcription and expression and making them possible candidates for binding sites of transcription factors, enzymes, and other proteins.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Shifting the MLCT of d 6 metal complexes to the red and NIR

Light-active d 6 -coordination compounds hold great promise for light energy conversion, sensors and therapeutic applications. However, the activity in the red-to-NIR spectral region is highly desirable to convert solar light more efficiently, use low-cost red-light sources and activate these chromophores in biological tissue environment. Due to their versatility, tunability and broad intense absorption, d 6 -coordination compounds with metalto-ligand charge transfer (MLCT) transitions are especially interesting. This review article offers a comprehensive collection of strategies to tune MLCT excited states in d 6 metal complexes and gives insights on group 6 to group 9 transition metals and their respective state-of-the-art MLCT engineering towards red-shifted absorption and emission properties with long-lived excited states. Strategies comprise lowering the π* level of the ligands, destabilizing and mixing of the metal-based HOMO, switching within a group of transition metals, matrix effects and insights into dealing with excited state deactivation in the context of the energy gap law.

Metal to ligand charge transfer (MLCT)↗
DOE OSTI2016

Calcining natural zeolites to improve their effect on cementitious mixture workability

Despite the benefits to long-term concrete durability, the use of natural zeolites as supplementary cementitious materials (SCMs) is uncommon due to their high water demand. The motivation of the research presented here was to better understand how the physical and chemical characteristics of natural zeolites influenced the workability of cementitious mixtures and whether those properties could be modified through calcination to mitigate the high water demand of natural zeolites. In this research, three different natural zeolites were characterized in their original and calcined states using x-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) surface area measurements. Rheology experiments were then conducted on cementitious pastes containing these natural zeolites, in their original and calcined states, to assess mixture viscosity and yield stress. Results showed that calcination destabilized the structure of the natural zeolites and reduced their surface area, which led to an improvement in mixture viscosity and yield stress.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Effect of magnesium on calcium silicate hydrate (C-S-H)

The addition of MgCl{sub 2} to synthetic calcium silicate hydrate (C-S-H) with Ca/Si = 0.8 lowers the pH values below 10. Experimental observations and thermodynamic calculations show the destabilization of C-S-H and the precipitation of magnesium silicate hydrate (M-S-H). In contrast, the addition of MgO to C-S-H increases the pH values up to 11.5 and the Ca/Si in C-S-H from 0.8 to ~ 1.0. At high pH, the formation of M-S-H and brucite is observed experimentally. Less brucite is present at 50 than at 20 °C indicating a slow dissolution kinetic of brucite at 20 °C. Thermodynamic modelling is in good agreement with the changes in C-S-H and M-S-H formation in the presence of MgO although no brucite is predicted. M-S-H is observed in the presence of both MgCl{sub 2} and MgO, is stable from pH 7.5 to 11.5 and has a structure comparable to the structure of M-S-H prepared from MgO and SiO{sub 2} only.

36 MATERIALS SCIENCE↗
DOE OSTI2021

The effect of equilibration time on Al uptake in C-S-H

Calcium silicate hydrate (C-S-H) is the main hydration product of Portland cements. The partial replacement of Portland cements by supplementary cementitious materials can result in C-S-H with lower Ca/Si ratios and more aluminum and alkalis. The effect of equilibration time on Al uptake in C-S-H was investigated using equilibration times from 7 days up to 3 years. Lower Al concentrations were measured in the solution after longer equilibration times. In addition, a higher uptake of Al in C-S-H was observed based on the decrease in the content of secondary phases. Little further decrease in Al concentrations was observed after 2 years and longer at low Ca/Si. At high Ca/Si no significant change in solution concentrations was observed after more than 3 month, while the destabilization of secondary phases continued up to 1 year, indicating that a (meta)stable equilibrium was reached faster at higher Ca/Si ratios.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Ab initio thermodynamics of magnesium carbonates and hydrates in water-saturated supercritical CO2 and CO2-rich regions

ab initio thermodynamics is used to determine how free energies of magnesium carbonates and hydrates in a CO2–rich environment change with water concentration across a range of temperature and pressure relevant to geochemistry and carbon sequestration (275 K to 375 K and pCO2 of 1 to 210 bar). The methodology is based on first principles density-functional theory (DFT) calculations of the total energies and vibrational entropy of periclase, magnesite, brucite, nesquehonite, and hydromagnesite coupled to the experimental chemical potentials of CO2 and H2O. The impact of water in supercritical CO2 (scCO2), even though less than 1% at saturation, is found to have a significant impact on the stability of hydrated carbonate minerals. Hydromagnesite and nesquehonite are found to be more thermodynamically stable than periclase and brucite in water-saturated scCO2 and hence may be expected to result kinetically from carbonation of these minerals during CO2 sequestration. Under dehydrating conditions nesquehonite destabilizes rapidly, whereas hydromagnesite is much more likely to persist in a CO2-rich environment, consistent with the observations that hydromagnesite is widespread in nature and nesquehonite is relatively rare.

Chaka, Anne M.↗
DOE OSTI2025

Mixed lipid bilayers enable enhanced stability and activity retention of Lipase A in low-pH environments

Lipase A (LipA) from Bacillus subtilis is a versatile and industrially relevant enzyme, but its activity is compromised under acidic conditions due to aggregation and deactivation. In this study, we investigated the use of mixed lipid bilayers to stabilize and improve activity retention of LipA at low pH. Attachment to lipid bilayers, particularly those containing cationic lipids, greatly enhanced the long-term stability of LipA in acidic conditions while also leading to improvements in activity. Tethering to cationic bilayers not only shifted the apparent pH activity profile toward more acidic conditions, but also significantly enhanced activity retention upon incubation at pH 6. Notably, this protective effect persisted even without direct tethering, indicating that reversible, non-covalent interactions with the bilayer surface are sufficient for long-term stability. Circular dichroism further revealed that the secondary structure of LipA was retained, while dynamic light scattering suggested that activity loss in solution was primarily due to aggregation of the native state. Together, these findings support a model in which lipid bilayers mitigate aggregation and stabilize LipA through transient interactions and electrostatic modulation of the local surface environment. Furthermore, this approach exemplifies a simple, tether-free strategy for enhancing enzyme performance in acidic or destabilizing conditions, with implications for biocatalysis, biosensing, and therapeutic delivery.

Biocatalysis↗
DOE OSTI2020

The compositional optimization and secondary phases evaluation regarding the creep resistance in Grade 91 steel through the CALPHAD approach

The critical secondary phases along with critical temperatures in regard to the creep resistance of Grade 91 steel alloy were evaluated in order to optimize the composition of the alloy to improve the creep resistance. The critical temperatures which are highlighted in this paper are Ac1 (the threshold temperature in which austinite begins to form), and Ac3 (the threshold temperature at which ferrite is fully transformed into austenite). Furthermore, optimization was presented through various Cr, V, Nb, and N concentrations in Gr.91 in relation to these critical temperatures and the mole fraction of M 23 C 6 , MX, and Z-Phase as critical secondary phases. Here, the results indicate that increasing V and Nb will increase MX stability, whereas decreasing Cr and N lead to a decrease in Z-Phase and M 23 C 6 stability, which may lead to an increased creep resistance of the material. Upon further analyzing the V, Nb, and N concentrations in Gr.91, results indicate that increasing Nb content in the steel can lead to an increased stability of Nb-rich MX2 carbide which can be used to replace Z-Phase in low N steels. Simulation results indicate that elimination of N with a dramatic increase in Nb concentrations result in the stability increase of only M 23 C 6 and MX2 phases at temperature regions between 600 °C and 1370 °C and a complete removal of Z-Phase precipitation. Overall, with the elimination of N, which destabilizes Z-Phase precipitation, and an increase in Nb for NbC carbide stability, a possible solution to increasing both long-term and short-term creep resistance for Gr.91 can be achieved, though further optimization and creep experiments need to be conducted for final conclusions.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Landslide monitoring using seismic refraction tomography – The importance of incorporating topographic variations

Seismic refraction tomography provides images of the elastic properties of subsurface materials in landslide settings. Seismic velocities are sensitive to changes in moisture content, which is a triggering factor in the initiation of many landslides. However, the application of the method to long-term monitoring of landslides is rarely used, given the challenges in undertaking repeat surveys and in handling and minimizing the errors arising from processing time-lapse surveys. This work presents a simple method and workflow for producing a reliable time-series of inverted seismic velocity models. This method is tested using data acquired during a recent, novel, long-term seismic refraction monitoring campaign at an active landslide in the UK. Potential sources of error include those arising from inaccurate and inconsistent determination of first-arrival times, inaccurate receiver positioning, and selection of inappropriate inversion starting models. At our site, a comparative analysis of variations in seismic velocity to real-world variations in topography over time shows that topographic error alone can account for changes in seismic velocity of greater than ±10% in a significant proportion (23%) of the data acquired. The seismic velocity variations arising from real material property changes at the near-surface of the landslide, linked to other sources of environmental data, are demonstrated to be of a similar magnitude. Over the monitoring period we observe subtle variations in the bulk seismic velocity of the sliding layer that are demonstrably related to variations in moisture content. This highlights the need to incorporate accurate topographic information for each time-step in the monitoring time-series. The goal of the proposed workflow is to minimize the sources of potential errors, and to preserve the changes observed by real variations in the subsurface. Following the workflow produces spatially comparable, time-lapse velocity cross-sections formulated from disparate, discretely-acquired datasets. These practical steps aim to aid the use of the seismic refraction tomography method for the long-term monitoring of landslides prone to hydrological destabilization.

Whiteley, J. S.↗
DOE OSTI2019

Stress evolution in lithium metal electrodes

The potential advantages of lithium metal anodes have received widespread attention (highest capacity, lowest reduction potential, etc). However, the poor stability of Li metal / liquid electrolyte interfaces leads to chronic problems, such as dendrite formation and capacity loss. The possible impact of mechanical effects on interface stability and dendrite formation are difficult to probe directly. In this study, stress evolution during lithium plating and stripping was monitored with precise in situ measurements. The data obtained with different film thicknesses made it possible to separate the stresses associated with the lithium metal and the solid electrolyte interphase (SEI). The results show that significant stresses are created in the SEI films. Based on this, a basic model of wrinkling-ratcheting-delamination is also presented. This analysis indicates that plasticity in a growing Li film can enhance surface wrinkling, and thus lead to morphological destabilization of a planar growth front.

25 ENERGY STORAGE↗
DOE OSTI2018

Carbonate stability in the reduced lower mantle

Carbonate minerals are important hosts of carbon in the crust and mantle with a key role in the transport and storage of carbon in Earth’s deep interior over the history of the planet. Whether subducted carbonates efficiently melt and break down due to interactions with reduced phases or are preserved to great depths and ultimately reach the core-mantle boundary remains controversial. In this study, experiments in the laser-heated diamond anvil cell (LHDAC) on layered samples of dolomite (Mg,Ca)CO3 and iron at pressure and temperature conditions reaching those of the deep lower mantle show that carbon-iron redox interactions destabilize the MgCO3 component, producing a mixture of diamond, Fe7C3, and (Mg,Fe)O. However, CaCO3 is preserved, supporting its relative stability in carbonate-rich lithologies under reducing lower mantle conditions. These results constrain the thermodynamic stability of redox-driven breakdown of carbonates and demonstrate progress towards multiphase mantle petrology in the LHDAC at conditions of the lowermost mantle.

58 GEOSCIENCES↗
DOE OSTI2022

Sequences of seismic and aseismic slip on bimaterial faults show dominant rupture asymmetry and potential for elevated seismic hazard

Here we perform numerical simulations of sequences of earthquake and aseismic slip on planar rate and state faults separating dissimilar material within the 2-D plane strain approximation. We resolve all stages of the earthquake cycle from aseismic slip to fast ruptures while incorporating full inertia effects during seismic event propagation. We show that bimaterial coupling results in favorable nucleation site and subsequent asymmetric rupture propagation. We demonstrate that increasing the material contrast enhances this asymmetry leading to higher slip rates and normal stress drops in the preferred rupture propagation direction. The normal stress drop, induced by the bimaterial effect, leads to strong dynamic weakening of the fault and may destabilize the creeping region on a heterogeneous rate and state fault, resulting in extended rupture propagation. Such rupture penetration into creeping patches may lead to more frequent opening of earthquake gates, causing increased seismic hazard. Furthermore, bimaterial coupling may lead to irregular seismicity pattern in terms of event length, peak slip rates, and hypocenter location, depending on the properties of the creeping patches bordering the seismogenically active part of the fault. Our results highlight robust characteristics of bimaterial interfaces that persist over long sequence of events and suggest the need for further exploration of the role of material contrast in earthquake physics and models of seismic hazard.

58 GEOSCIENCES↗
DOE OSTI2021

Synchrophasor spoofing detection and remediation for wide-area damping control

Evolving cyber-attack threats put at risk automatic closed-loop systems to be incorporated in the smart grid. Wide-area control systems are particularly vulnerable to signal spoofing attacks due to sensor remoteness and dependence on satellite communication for time synchronization. A successful cyber-attack on a wide-area controller has the potential to reduce relative stability of the power system or worse, destabilize it. As such, detection algorithms must be deployed as defense against such attacks with the ability to autonomously correct for detected tampering or misoperation. The Spoof Catch and Restore Routine (SCR 2 ), a combination of three real-time spoof detectors, each requiring limited information about the plant, is reported here. Nonlinear simulations of a compromised wide-area control system deployed in the Western Interconnection show the effectiveness of SCR 2 in detecting both delay-type and counterfeit-type spoofing attacks on wide-area sensors.

42 ENGINEERING↗