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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 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Identification of over ten thousand candidate structured RNAs in viruses and phages

Structured RNAs play crucial roles in viruses, exerting influence over both viral and host gene expression. However, the extensive diversity of structured RNAs and their ability to act in cis or trans positions pose challenges for predicting and assigning their functions. While comparative genomics approaches have successfully predicted candidate structured RNAs in microbes on a large scale, similar efforts for viruses have been lacking. In this study, we screened over 5 million DNA and RNA viral sequences, resulting in the prediction of 10,006 novel candidate structured RNAs. These predictions are widely distributed across taxonomy and ecosystem. We found transcriptional evidence for 206 of these candidate structured RNAs in the human fecal microbiome. These candidate RNAs exhibited evidence of nucleotide covariation, indicative of selective pressure maintaining the predicted secondary structures. Our analysis revealed a diverse repertoire of candidate structured RNAs, encompassing a substantial number of putative tRNAs or tRNA-like structures, Rho-independent transcription terminators, and potentially cis-regulatory structures consistently positioned upstream of genes. In summary, our findings shed light on the extensive diversity of structured RNAs in viruses, offering a valuable resource for further investigations into their functional roles and implications in viral gene expression and pave the way for a deeper understanding of the intricate interplay between viruses and their hosts at the molecular level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Catabolic repression in early-diverging anaerobic fungi is partially mediated by natural antisense transcripts

We report that early-diverging anaerobic fungi (order: Neocallimastigomycota), lignocelluolytic chytrid-like fungi central to fiber degradation in the digestive tracts of large herbivores, are attractive sources of cellulases and hemicellulases for biotechnology. Enzyme expression is tightly regulated and coordinated through mechanisms that remain unelucidated to optimize hydrolytic efficiency. Our analysis of anaerobic fungal transcriptomes reveals hundreds of cis-natural antisense transcripts (cis-NATs), which we hypothesize play an integral role in this regulation. Through integrated genomic and transcriptomic sequencing on a range of catabolic substrates, we validate these NATs in three species (Anaeromyces robustus, Neocallimasix californiae, and Piromyces finnis), and analyze their expression patterns and prevalence to gain insight into their function. NAT function was diverse and conserved across the three fungal genomes studied, with 10% of all metabolic process NATs associated with lignocellulose hydrolysis. Despite these similarities, however, only eleven gene targets were conserved orthologs. Several NATs were dynamically regulated by lignocellulosic substrates while their gene targets were unregulated. This observation is consistent with a hypothesized, but untested, regulatory mechanism where selected genes are exclusively regulated at the transcriptional/post-transcriptional level by NATs. However, only genes with high NAT relative expression levels displayed this phenomenon, suggesting a selection mechanism that favors larger dynamic ranges for more precise control of gene expression. In addition to this mode, we observed two other possible regulatory fates: canonical transcriptional regulation with no NAT response, and positive co-regulation of target mRNA and cognate NAT, which we hypothesize is a fine-tuning strategy to locally negate control outputs from global regulators. In conclusion, our work reveals the complex contributions of antisense RNA to the catabolic response in anaerobic fungi, highlighting its importance in understanding lignocellulolytic activity for bioenergy applications. More importantly, the relative expression of NAT to target may form a critical determinant of transcriptional vs post-transcriptional (NAT) control of gene expression in primitive anaerobic fungi.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Investigation on the solidification of several pure cyclic and aromatic hydrocarbons at pressures to 300 MPa

The effect of pressure on the solidification of several saturated cyclic hydrocarbons and three xylene isomers are experimentally determined with a variable-volume view cell at pressures to 300 MPa and temperatures starting at 293.15 K. Solid–liquid transitions are observed for cyclooctane, cis-1,2-dimethylcyclohexane, trans-1,4-dimethylcyclohexane, p-xylene, o-xylene, and 2-methylnaphthalene. However, methylcyclohexane, ethylcyclohexane, cis-1,4-dimethylcyclohexane, and m-xylene remained liquid over the same operating pressure and temperature ranges. The experimental solid–liquid transition data are well represented with two empirical equations, the Simon equation and a 2nd-order polynomial equation. Data obtained in this study agree with literature data within ±0.4% for 2-methylnaphthalene and ±0.2% for p-xylene.

02 PETROLEUM↗
DOE OSTI2019

A new calibration implementation for Doppler Coherence Imaging Spectroscopy

A new widely tunable, continuous-wave laser named C-Wave enables direct calibration at the unshifted, center-of-mass wavelength for most plasma lines in the range between 450 and 650 nm for Doppler Coherence Imaging Spectroscopy. It also provides the ability to scan around each desired wavelength over a small range of ±50pm, thus enabling an easy way to translate the measured phase difference ΔΦ of the diagnostic to the desired Doppler line shift Δλ, that corresponds to the physical parameter of interest, the particle velocity of an observed plasma species. A first wavelength scan of the C-Wave laser ±50pm around a single plasma line of interest, C III at 464.881 nm, is presented and compared to a simulated wavelength scan. It demonstrates not only the C-Wave capability as a Doppler CIS calibration source, but also its potential to immensely simplify Doppler CIS analysis for nearly all visible plasma lines of interest.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2025

In planta production of the nylon precursor beta-ketoadipate

Beta-ketoadipate (βKA) is an intermediate of the βKA pathway involved in the degradation of aromatic compounds in several bacteria and fungi. Beta-ketoadipate also represents a promising chemical for the manufacturing of performance-advantaged nylons. We established a strategy for the in planta synthesis of βKA via manipulation of the shikimate pathway and the expression of bacterial enzymes from the βKA pathway. Using Nicotiana benthamiana as a transient expression system, we demonstrated the efficient conversion of protocatechuate (PCA) to βKA when plastid-targeted bacterial-derived PCA 3,4-dioxygenase (PcaHG) and 3-carboxy-cis,cis-muconate cycloisomerase (PcaB) were co-expressed with 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (AroG) and 3-dehydroshikimate dehydratase (QsuB). This metabolic pathway was reconstituted in Arabidopsis by introducing a construct (pAtβKA) with stacked pcaG, pcaH, and pcaB genes into a PCA-overproducing genetic background that expresses AroG and QsuB (referred as QsuB-2). The resulting QsuB-2 x pAtβKA stable lines displayed βKA titers as high as 0.25 % on a dry weight basis in stems, along with a drastic reduction in lignin content and improvement of biomass saccharification efficiency compared to wild-type controls, and without any significant reduction in biomass yields. Using biomass sorghum as a potential crop for large-scale βKA production, techno-economic analysis indicated that βKA accumulated at titers of 0.25 % and 4 % on a dry weight basis could be competitively priced in the range of $2.04-34.49/kg and $0.47-2.12/kg, respectively, depending on the selling price of the residual biomass recovered after βKA extraction. This study lays the foundation for a more environmentally-friendly synthesis of βKA using plants as production hosts.

Kazaz, Sami↗
DOE OSTI2015

Spatial and temporal dynamics of organohalide-respiring bacteria in a heterogeneous PCE–DNAPL source zone

Effective treatment of sites contaminated with dense non-aqueous phase liquids (DNAPLs) requires detailed understanding of the microbial community responses to changes in source zone strength and architecture. Changes in the spatial and temporal distributions of the organohalide-respiring Dehalococcoides mccartyi ( Dhc ) strains and Geobacter lovleyi strain SZ ( GeoSZ ) were examined in a heterogeneous tetrachloroethene- (PCE-) DNAPL source zone within a two-dimensional laboratory-scale aquifer flow cell. As part of a combined remedy approach, flushing with 2.3 pore volumes (PVs) of 4% (w/w) solution of the nonionic, biodegradable surfactant Tween® 80 removed 55% of the initial contaminant mass, and resulted in a PCE–DNAPL distribution that contained 51% discrete ganglia and 49% pools (ganglia-to-pool ratio of 1.06). Subsequent bioaugmentation with the PCE-to-ethene-dechlorinating consortium BDI-SZ resulted in cis -1,2-dichloroethene (cis-DCE) formation after 1 PV (ca. 7 days), while vinyl chloride (VC) and ethene were detected 10 PVs after bioaugmentation. Maximum ethene yields (ca. 90 μM) within DNAPL pool and ganglia regions coincided with the detection of the vcrA reductive dehalogenase (RDase) gene that exceeded the Dhc 16S rRNA genes by 2.0 ± 1.3 and 4.0 ± 1.7 fold in the pool and ganglia regions, respectively. Dhc and GeoSZ cell abundance increased by up to 4 orders-of-magnitude after 28 PVs of steady-state operation, with 1 to 2 orders-of-magnitude increases observed in close proximity to residual PCE–DNAPL. These observations suggest the involvement of these dechlorinators the in observed PCE dissolution enhancements of up to 2.3 and 6.0-fold within pool and ganglia regions, respectively. Analysis of the solid and aqueous samples at the conclusion of the experiment revealed that the highest VC (≥ 155 μM) and ethene (≥ 65 μM) concentrations were measured in zones where Dhc and GeoSZ were predominately attached to the solids. In conclusion, these findings demonstrate dynamic responses of organohalide-respiring bacteria in a heterogeneous DNAPL source zone, and emphasize the influence of source zone architecture on bioremediation performance.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

A Structural Basis for Reversible Photoswitching of Absorbance Spectra in Red Fluorescent Protein rsTagRFP

rsTagRFP is the first monomeric red fluorescent protein (FP) with reversibly photoswitchable absorbance spectra. The switching is realized by irradiation of rsTagRFP with blue (440 nm) and yellow (567 nm) light, turning the protein fluorescence ON and OFF, respectively. It is perhaps the most useful probe in this color class that has yet been reported. Because of the photoswitchable absorbance, rsTagRFP can be used as an acceptor in photochromic Foerster resonance energy transfer. Yellow FPs, YPet and mVenus, are demonstrated to be excellent photochromic Foerster resonance energy transfer donors for the rsTagRFP acceptor in its fusion constructs. Analysis of X-ray structures has shown that photoswitching of rsTagRFP is accompanied by cis-trans isomerization and protonation/deprotonation of the chromophore, with the deprotonated cis- and protonated trans-isomers corresponding to its ON and OFF states, respectively. Unlike in other photoswitchable FPs, both conformers of rsTagRFP chromophore are essentially coplanar. Two other peculiarities of the rsTagRFP chromophore are an essentially hydrophobic environment of its p-hydroxyphenyl site and the absence of direct hydrogen bonding between this moiety and the protein scaffold. The influence of the immediate environment on rsTagRFP chromophore was probed by site-directed mutagenesis. Residues Glu145 and His197 were found to participate in protonation/deprotonation of the chromophore accompanying the photoswitching of rsTagRFP fluorescence, whereas residues Met160 and Leu174 were shown to spatially restrict chromophore isomerization, favoring its radiative decay.

08 HYDROGEN↗
DOE OSTI2012

Crystal structure and chemical bonding of novel Li-containing polar intermetallic compound La{sub 11}Li{sub 12}Ge{sub 16}

A novel Li-containing polar intermetallic compound La{sub 11}Li{sub 12}Ge{sub 16} has been synthesized using the high-temperature reaction method and characterized by both powder and single-crystal X-ray diffractions. The title compound crystallized in the orthorhombic crystal system (space group Immm, Z=2, Pearson symbol oI78) with fifteen crystallographically unique atomic positions in the asymmetric unit, and the lattice parameters are refined as a=4.5244(4) A, b=6.9932(6) A, and c=53.043(5) A. The complex crystal structure of the title compound can be described as a 2:1 intergrowth of two closely related compounds: La{sub 2}Li{sub 2}Ge{sub 3} (Ce{sub 2}Li{sub 2}Ge{sub 3}-type) and La{sub 3}Li{sub 4}Ge{sub 4} (Zr{sub 3}Cu{sub 4}Si{sub 4}-type) acting like 'building-blocks' along the c-axis. Six La sites are categorized into three distinct types based on the local coordination environment showing the coordination numbers of 12-14. Three unique Li sites are placed in the centers of local tetrahedra formed by four Ge atoms which eventually construct Ge{sub 2} dimers or 1-dimensional cis-/trans-Ge chains. Theoretical investigations using the tight-binding linear muffin-tin orbital (LMTO) method provide rationales for an improved structural stability and for unique local coordination geometries established by anionic elements including [LiGe{sub 4}] tetrahedra, cis-/trans-Ge chain and Ge{sub 2} dimers. - Graphical abstract: Reported is a novel ternary Li-containing polar intermetallic compound La{sub 11}Li{sub 12}Ge{sub 16}. The complex crystal structure can be viewed as a simple combination of two closely related known compounds acting as 'building-blocks', La{sub 2}Li{sub 2}G{sub 3} and La{sub 3}Li{sub 4}Ge{sub 4}, in a 2:1 stoichiometric ratio. Highlights: Black-Right-Pointing-Pointer A novel Li-containing polar intermetallic compound La{sub 11}Li{sub 12}Ge{sub 16} was synthesized. Black-Right-Pointing-Pointer The complex crystal structure was easily explained as a combination of two known compounds. Black-Right-Pointing-Pointer Theoretical calculations indicated that the Fermi level was located near the pseudogap.

36 MATERIALS SCIENCE↗
DOE OSTI2013

Ce{sub 2}AgYb{sub 5/3}Se{sub 6}, La{sub 2}CuErTe{sub 5}, and Ce{sub 2}CuTmTe{sub 5}: Three new quaternary interlanthanide chalcogenides

Three new ordered quaternary interlanthanide chalcogenides, Ce{sub 2}AgYb{sub 5/3}Se{sub 6}, La{sub 2}CuErTe{sub 5}, and Ce{sub 2}CuTmTe{sub 5}, have been prepared by direct reaction of the elements in molten NaBr at 900 Degree-Sign C. Each compound forms a new structure-type. The Ce{sub 2}AgYb{sub 5/3}Se{sub 6} structure consists of {infinity}{sup 2}{l_brace} [AgYb{sub 5/6}Se{sub 6}]{sup 6-}{r_brace} layers intercalated by Ce{sup 3+} cations. These layers are composed of {infinity}{sup 1}{l_brace} [Yb{sub 5/3}Se{sub 6}]{sup 7-}{r_brace} quadruplet ribbons of [YbSe{sub 6}]{sup 9-} octahedra and infinite {infinity}{sup 1}{l_brace} [AgSe{sub 6}]{sup 11-}{r_brace} double chains of [AgSe{sub 5}]{sup 9-}. The La{sub 2}CuErTe{sub 5} structure is made of one-dimensional {infinity}{sup 1}{l_brace} [CuErTe{sub 5}]{sup 6-}{r_brace} ribbons separated by La{sup 3+} cations. These ribbons are formed by cis-edge sharing {infinity}{sup 1}{l_brace} [CuTe{sub 2}]{sup 3-}{r_brace} tetrahedral chains and trans-edge sharing {infinity}{sup 1}{l_brace} [ErTe{sub 4}]{sup 5-}{r_brace} chains. While La{sub 2}CuErTe{sub 5} crystallizes in the orthorhombic space group Pnma, Ce{sub 2}CuTmTe{sub 5} crystallizes in the monoclinic space group C2/m. The latter crystal structure is assembled from {infinity}{sup 2}{l_brace} [CuTmTe{sub 5}]{sup 6-}{r_brace} layers intercalated by Ce{sup 3+} cations. These layers consist of single {infinity}{sup 1}{l_brace} [TmTe{sub 4}]{sup 5-}{r_brace} chains connected to each other through dimers or pseudo-double chains. - Graphical abstract: [CuTe{sub 4}]{sup 7-} tetrahedra sharing cis-edges to yield chains in the La{sub 2}CuErTe{sub 5}. Highlights: Black-Right-Pointing-Pointer New ordered interlanthanide tellurides. Black-Right-Pointing-Pointer New quaternary chalcogenides. Black-Right-Pointing-Pointer Low-dimensional lanthanide chalcogenide substructures. Black-Right-Pointing-Pointer Flux synthesis of new chalcogenides.

36 MATERIALS SCIENCE↗
DOE OSTI2017

The assembly of two isomorphous coordination compounds based on 1,4-cyclohexanedicarboxylic acid and 2,4-diamino-6-phenyl-1,3,5-triazine

The compounds [Co(e,a-cis-1,4-chdc)(phdat)]{sub n} (1) and [Cd(e,a-cis-1,4-chdc)(phdat)]{sub n} (2) have been synthesized under hydrothermal method by using 1,4-cyclohexanedicarboxylic acid (1,4-H{sub 2}chdc), 2,4-diamino-6-phenyl-1,3,5-triazine (phdat) as well as CoCl{sub 2}·6H{sub 2}O, CdCl{sub 2}·2.5H{sub 2}O respectively and characterized by IR spectra, X-ray single-crystal diffraction, powder X-ray single-crystal diffraction (PXRD), elemental analyses and thermogravimetric analyses (TGA). The results show the compounds 1 and 2 are isomorphous and exhibit paddle-wheel dinuclear Co{sub 2}(CO{sub 2}){sub 4}/Cd{sub 2}(CO{sub 2}){sub 4} units, which are further connected to 1D chain structures by μ{sub 4}:η{sup 1}:η{sup 1}:η{sup 1}:η{sup 1} 1,4-chdc{sup 2–} ligands and extended into a 3D structures via different hydrogen bonding and π…π stacking interactions. Furthermore, compound 1 exhibits antiferromagnetic behavior and compound 2 displays luminescent behavior at solid state. - Graphical abstract: Two isomorphous coordination compounds 1–2 have been synthesized and characterized by XRD, IR spectra and TGA etc. Compound 1 and 2 display antiferromagnetic behavior and luminescent behavior respectively. - Highlights: • Two novel polymers based on 1,4-cyclohexanedicarboxylic acid have been synthesized. • Compounds 1 and 2 feather 1D chain structure built up from paddle-wheel SBUs. • The magnetism of 2 is investigated. • The electrochemical property and luminescent property of 1 are investigated.

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

A melting-like process and the local structures during the anatase-to-rutile transition

Highlights: • The maximum size of anatase crystallites is more useful to describe the phase stability than the traditional critical size. • The melting-like process accelerates the phase transition from anatase to rutile. • The cis-coordinated anatase is transformed to trans-coordinated rutile by torsion & rotation of TiO{sub 6} octahedra in anatase. Phase transition of titanium oxide from anatase to rutile was investigated by using transmitted electron microscope (TEM), scanning electron microscope (SEM) and X-ray diffraction (XRD), in combination with the atomic pair distribution function (PDF) technique. The transition range is about 528–805 °C and the critical size is ~73 nm for the sol-gel samples calcined for 6 h. A melting-like process was evidently observed in the transition samples by SEM and it will speed up the phase transition. PDF reveals that anatase crystallites are packed by neighbouring TiO{sub 6} octahedra in a cis-coordinated way. Anatase crystallites larger than the critical size will be unstable and transform into rutile in a trans-coordinated way by torsion and rotation of part of octahedra and it will rapidly spread the entire crystallites driven by a melting-like process. We suggest the maximum size of anatase will be more technically useful for the description of the phase stability from anatase to rutile because unstable small anatase crystals are consumed during longer calcination process to grow the larger anatase crystals.

36 MATERIALS SCIENCE↗
DOE OSTI2012

Microwave-assisted synthesis and photovoltaic measurements of CuInS{sub 2} nanoparticles prepared by using metal–organic precursors

Highlights: ► CuInS{sub 2} nanoparticles were prepared using complexes via a microwave-assisted method. ► The effect of preparation parameters on the morphology of CuInS{sub 2} was investigated. ► The as-deposited CdS/CuInS{sub 2} films were used for the photovoltaic measurements. -- Abstract: In this work, CuInS{sub 2} (CIS) nanoparticles have been synthesized with the aid of (1,8-diamino-3,6-dioxaoctan)copper(II) sulfate ([Cu(DADO)]SO{sub 4}) and bis(propylenediamine)copper(II) sulfate ([Cu(pn){sub 2}]SO{sub 4}) complexes as copper precursor in the presence of microwave irradiation. Besides, L-cystine, InCl{sub 3}, and sodium dodecyl sulfate (SDS) were applied as sulfur source, indium precursor, and capping agent, respectively. To investigate the effect of preparation parameters like microwave power and irradiation time on the morphology and particle size of CuInS{sub 2}, the experiment was carried out at different conditions. The as-synthesized CuInS{sub 2} nanoparticles were characterized by XRD, FT-IR, PL, SEM, TEM, and EDS. The XRD results showed that pure tetragonal CuInS{sub 2} could be only obtained after annealing at 400 °C for 2 h. The SEM images indicated that with decreasing the microwave power and irradiation time, particle size of CuInS{sub 2} nanoparticles decreased. To fabricate a solar cell, CdS film was directly deposited on top of the CIS film prepared by Doctor's blade method through chemical bath deposition. The as-deposited CdS/CuInS{sub 2} films were used for the photovoltaic measurements.

36 MATERIALS SCIENCE↗
DOE OSTI2013

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V{sub 10}, V{sub 30}, and V{sub 50} values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2019

Calibrated helium and carbon ion flow measurements in the DIII-D divertor plasma

To explore the influence of drifts on ion flows in the DIII-D divertor and Scrape-Off-Layer (SOL), a calibrated Coherence Imaging System (CIS) views the lower divertor. A new tuneable calibration laser and precision wavemeter provide the rest wavelength for CIII 465 nm plasma emissions resulting in ≤ 1 km/s uncertainty in ion velocities that are in the range of 30 km/s in the divertor plasma. The 2-D line-integrated velocity images have been tomographically inverted to obtain maps of ion velocity. Both He + and C 2+ ion velocity maps were measured in both directions of the toroidal magnetic field B T , and C 2+ images were obtained in attached and detached L- and H-mode plasmas. The measured C 2+ velocities are in the range of 20-30km/s and are compared with UEDGE modeling with full drifts. While He II as a main ion is expected to be entrained in the plasma flow, the C 2+ impurity flow involves the competition between the frictional and ion temperature gradient forces. Both the CIS data and UEDGE modeling agree that the C 2+ flow is towards the divertor plates, but flips with the direction of B T . In general, the experimental C 2+ emission and flow profiles have a wider spatial extent than the UEDGE modeling.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2012

Ru L[subscript 2,3] XANES theoretical simulation with DFT: A test of the core-hole treatment

Density functional theory (DFT)-based relativistic calculations were performed to model the Ru L-edge X-ray absorption near edge structure (XANES) spectra of the hexaammineruthenium complex [Ru(NH{sub 3}){sub 6}]{sup 3+} and 'blue dimer' water oxidation catalyst, cis,cis- [(bpy){sub 2}(H{sub 2}O)Ru{sup III}ORu{sup III}(OH{sub 2})(bpy){sub 2}]{sup 4+} (bpy is 2,2-bipyridine). Two computational approaches were compared: simulations without the core-hole and by modeling of the core-hole within the Z+1 approximation. Good agreement between calculated and experimental XANES spectra is achieved without including the core-hole. Simulations with algorithms beyond the Z+1 approximation were only possible in a framework of the scalar relativistic treatment. Time-dependent DFT (TD-DFT) was used to compute the Ru L-edge spectrum for [Ru(NH{sub 3}){sub 6}]{sup 3+} model compound. Three different core-hole treatments were compared in a real-space full multiple scattering XANES modeling within the Green function formalism (implemented in the FEFF9.5 package) for the [Ru(Mebimpy)(bpm)(H{sub 2}O)]{sup 2+} complex. The latter approaches worked well in cases where spin-orbit treatment of relativistic effects is not required.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2023

Epitope topography of agonist antibodies to the checkpoint inhibitory receptor BTLA

B and T lymphocyte attenuator (BTLA) is an attractive target for a new class of therapeutics that attempt to rebalance the immune system by agonizing checkpoint inhibitory receptors (CIRs). Herpesvirus entry mediator (HVEM) binds BTLA in both trans- and cis-orientations. We report here the development and structural characterization of three humanized BTLA agonist antibodies, 22B3, 25F7, and 23C8. We determined the crystal structures of the antibody-BTLA complexes, showing that these antibodies bind distinct and non-overlapping epitopes of BTLA. While all three antibodies activate BTLA, 22B3 mimics HVEM binding to BTLA and shows the strongest agonistic activity in functional cell assays and in an imiquimod-induced mouse model of psoriasis. 22B3 is also capable of modulating HVEM signaling through the BTLA-HVEM cis-interaction. The data obtained from crystal structures, biochemical assays, and functional studies provide a mechanistic model of HVEM and BTLA organization on the cell surface and informed the discovery of a highly active BTLA agonist.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

60 APPLIED LIFE SCIENCES↗