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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 1,063 records · Page 59
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Development of Repeatable Microcatheter Access Port for Intra-arterial Therapy of Liver Cancer

Purpose: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer. Materials and Methods: The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port–catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed. Results: In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation. Conclusion: The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Multiple Bifurcated Covered Self-Expanding Metallic Stents for Complex Tracheobronchial Fistulas or Stenosis

Objective: We aimed to determine the safety and feasibility of bifurcated covered self-expanding stents for the treatment of complex tracheobronchial fistulas or stenosis. Methods: Twenty-eight patients were treated by multiple bifurcated covered airway stents (Micro-Tech Co. Ltd., Nanjing, China), including 18 cases of gastrobronchial or gastrotracheal fistula, 6 cases of bronchopleural fistula and 4 cases of severe tracheobronchial stenosis. The large bifurcated covered stent was placed at the main carina, and the small stents were inserted into primary right carina or secondary left carina. Clinical and imaging data were retrospectively analyzed. Results: Stents were successfully inserted in 27 patients at the first attempt. In total, 29 large bifurcated covered stents, 27 small bifurcated covered stents and 5 small bifurcated covered single-plugged stents were inserted. All patients with fistula could resume eating without coughing after the procedure. No perioperative death or severe complications occurred. Two patients underwent stent removal due to intolerance of stenting; the clinical success rate was 93% (26/28). Nineteen complications were found in 12 patients; 8 patients needed stent removal or replacement, for a major complication rate of 29% (8/28). Eight patients underwent successful stent removal due to complications. Fifteen patients died of tumors and one patient died of pulmonary infection. The median survival was 33 months. Fistula recurrence was found in one patient 5 months after stenting, and second small bifurcated covered stent was inserted. Conclusions: Multiple bifurcated covered metallic stenting is effective and safe for complex tracheobronchial fistulas or stenosis, with good symptom palliation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Ab initio modeling of transport and thermodynamic stability for hafnia memristive devices

HfO 2 -based memristive switching devices are currently under intensive investigation due to their high performance and mature fabrication techniques. However, several critical issues have to be addressed to bring them from lab to market. We have recently looked into two important issues with the use of density functional theory methods. One is the wide distribution of device resistance in off-states. We have modeled the switching process of a Pt-HfO 2 -Pt structure for which quantized conductance was observed. Oxygen atoms moving inside a conductive oxygen vacancy filament divide the filament into several quantum wells. Device conductance changes exponentially when one oxygen atom moves away from interface into filament. We propose that the high sensitivity of device conductance to the position of oxygen atoms results in the large variation of device off-state resistance. Another issue that we have recently addressed is the poor switching performance of devices based on a TiN-HfO 2 -TiN structure. While recent experiments have shown that by inserting an "oxygen scavenger" metal between positive electrode and oxide significantly improves device performance, the fundamental understanding of the improvement is lacking.We provide detailed understanding how scavenger layers improve device performance. First, we show that Ta insertion facilitates formation of on-states by reducing the formation energy. Second, the inserted Ta layer reduces the Schottky barrier height in the off-states by changing interface electric dipole at the oxide electrode interface. Nevertheless, the device maintains a high on/off resistance ratio. Finally, with Ta insertion the on-state conductance becomes much less sensitive to the specific location from which the oxygen was removed from the oxide. In conclusion, our studies provide fundamental understanding needed for enabling realization of a non-volatile memory technology with reduced energy consumption.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Development of a new control rod drive mechanism design for the ISU AGN-201M reactor

The Aerojet General Nucleonics (AGN) model 201-Modified, known as the AGN-201M reactor, plays an essential role in the educational and research activities at Idaho State University (ISU). The ISU AGN-201M's original Control Rod Drive Mechanism (CRDM) has been in operation for more than fifty years with no large-scale redesigns. The CRDM is required to eject the fuel rods within one second during a SCRAM event (also known as a 'reactor trip') and adjust the control rods' insertion speed, and keeps the rod insertion sequence correct. The existing control rod drive mechanisms meet these criteria but experience a few concerns due to aging. Concerns include complex maintenance and costly repairs for old electromechanical components, rod position feedback errors, and the impediment of the plate during a SCRAM due to binding of the lead screws of the existing mechanism. During a binding event, the drive mechanism becomes locked, preventing the control rod's magnetic plate from moving in or out under the reactor's normal and emergency operating conditions. Although, the binding has no effect on the ability of the rod to exit the core during the SCRAM. To counteract the concerns and issues with the current CRDM, a new design has been proposed using newer components and a simplified design. The new design utilizes more advanced electric and mechanical components that are commercially available. The new CRDM system is divided into four main aspects: (1) control rod movement design (motor, lead screw, guide rods), (2) control rod ejection (springs, electromagnet), (3) control rod position and feedback (position transducer, microswitches), and (4) material selection and structural analysis. The new design aims to reduce the overall complexity and probability of failure to improve the reactor's overall reliability. With proper material selection and improved structural design, the new drives are lighter with little to no change in structural integrity. The new control rod drive mechanism eliminates binding scenarios by using a single lead screw and implementing additional guide rods. An advanced linear position sensor and microswitches replace the existing and aging synchro system for accurate rod position feedback resulting in better reactivity control. The new design meets the reactor's operational limits by having an average reactivity insertion of 0.065% Δk/k per second, which corresponds to a total control rod insertion time of 19.23 s, while the control rod's ejection time remains less than one second during a SCRAM event. The new design ensures the reactor's long-term viability for educational and research activities by increasing the reliability and safety of operation for years to come.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2016

Detection of Sleeping Beauty transposition in the genome of host cells by non-radioactive Southern blot analysis

The Sleeping Beauty transposon (SB-Tn) system is being used widely as a DNA vector for the delivery of therapeutic transgenes, as well as a tool for the insertional mutagenesis in animal models. In order to accurately assess the insertional potential and properties related to the integration of SB it is essential to determine the copy number of SB-Tn in the host genome. Recently developed SB100X transposase has demonstrated an integration rate that was much higher than the original SB10 and that of other versions of hyperactive SB transposases, such as HSB3 or HSB17. In this study, we have constructed a series of SB vectors carrying either a DsRed or a human β-globin transgene that was encompassed by cHS4 insulator elements, and containing the SB100X transposase gene outside the SB-Tn unit within the same vector in cis configuration. These SB-Tn constructs were introduced into the K-562 erythroid cell line, and their presence in the genomes of host cells was analyzed by Southern blot analysis using non-radioactive probes. Many copies of SB-Tn insertions were detected in host cells regardless of transgene sequences or the presence of cHS4 insulator elements. Interestingly, the size difference of 2.4 kb between insulated SB and non-insulated controls did not reflect the proportional difference in copy numbers of inserted SB-Tns. We then attempted methylation-sensitive Southern blots to assess the potential influence of cHS4 insulator elements on the epigenetic modification of SB-Tn. Our results indicated that SB100X was able to integrate at multiple sites with the number of SB-Tn copies larger than 6 kb in size. In addition, the non-radioactive Southern blot protocols developed here will be useful to detect integrated SB-Tn copies in any mammalian cell type.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Sigma bond activation of deuterium mediated by atomic cerium cations: Experiment and theory

Reaction of ground-state Ce + (5d 2 4f 1 ) with deuterium in a reaction cell at a pressure of 1.5–4.0 Torr and temperatures ranging from approximately 265–515 K is studied. Rate constants for formation of CeD 2 + are acquired and vary from approximately 2.8 × 10 -14 to 2.1 ×10 -13 cm 3 /s. A negative temperature dependence is observed for the measured rate constants, indicating the reaction becomes less efficient as the temperature increases, consistent with an exothermic reaction. Electronic structure calculations were performed using density functional theory (DFT) at the PBE0 level to characterize all reactant and product species as well as to generate potential energy surfaces (PESs) for the insertion reaction. This combination of experimental and theoretical results suggest that Ce + inserts into the deuterium sigma bond in an overall exothermic and barrierless process.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2016

Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy

Purpose: To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. Methods and Materials: In this institutional review board–approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance–guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. Results: A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. Conclusions: Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Dynamic imaging of metastable reaction pathways in lithiated cobalt oxide electrodes

Understanding how lithium-ion batteries function down to the atomic level during charge and discharge cycling can provide valuable guidance to optimize structure-property relationships and to design and understand new electrode materials. Lithium insertion and reactions with the electrodes during charge and discharge cycling can occur via metastable structures with complex ordering and related non-equilibrium phenomena. Remarkably, these processes remain still poorly understood despite their significance in the operation of lithium battery systems in critical technologies. In this communication, we present the dynamics of lithium insertion into Co3O4 and the evolution of metastable phases as probed by in-situ transmission electron microscopy, in concert with first principles density functional theory calculations. We show that the initial lithium intercalation reaction occurs with the formation of several metastable and intermediate phases, followed by a sequence of conversion reactions that perturb and expand the cubic-close-packed oxygen array, ultimately generating an end-product of finely dispersed cobalt metal clusters within a Li2O matrix. The calculated non-equilibrium lithiation pathways corroborate with the experimental lithiation voltages, and explain the significant hysteresis that occurs during electrochemical cycling. The data provide new insights into the complexity of solid state lithium electrochemistry in metal oxides that are relevant to advancing lithium battery technology.

conversion reaction electrode↗
DOE OSTI2023

Ultrasonic measurement of temperature distributions in extreme environments: Electrical power plants testing in utility-scale steam generators

Thermal heterogeneities within energy conversion and storage, material processing, nuclear processes, aerospace, and military applications are often inaccessible to characterization by insertion sensors. When sensor deployment is possible, conventional pointwise temperature probes quickly degrade when inserted into harsh environments typical of such processes. We developed spatially-resolved ultrasonic thermometry to noninvasively measure the spatial distributions of thermal properties in such applications, even when sizable thermal gradients are present. Our method divides the path of ultrasonic propagation into segments bound by echogenic features, which create echoes in pulse-echo mode, encoding the information about interior temperature distributions. We use the acquired ultrasonic responses to estimate the internal temperature distributions by solving an inverse problem or concatenating segmental estimates. This work describes the implementation and industrial testing of the developed method at a coal-fired electrical power generation plant. We inserted an echogenically segmented Inconel 625 waveguide into the combustion zone of the utility-scale boiler and continuously acquired ultrasonic data while keeping sensitive components away from the damaging combustion environment. The accuracy of the time-dependent temperature distributions reconstructed from the ultrasonic measurements was comparable to that of thermocouples. The resiliency of ultrasonic thermometry to harsh combustion conditions was far superior to conventional insertion sensors. The measurements obtained during plant operation captured daily steam generation cycles in response to changing customer demand and intermittent contributions of renewable power sources to the power grid. These measurements have revealed new insights into the relationship between the dynamic power generation load and the conditions inside the steam generator. As a result, the successful industrial testing of spatially-resolved ultrasonic thermometry in solids indicates that the developed technology has matured to become an attractive alternative to conventional sensing in solving challenging problems of long-term thermal characterizations in extreme environments.

42 ENGINEERING↗
DOE OSTI2015

An alphavirus temperature-sensitive capsid mutant reveals stages of nucleocapsid assembly

Alphaviruses have a nucleocapsid core composed of the RNA genome surrounded by an icosahedral lattice of capsid protein. An insertion after position 186 in the capsid protein produced a strongly temperature-sensitive growth phenotype. Even when the structural proteins were synthesized at the permissive temperature (28 °C), subsequent incubation of the cells at the non-permissive temperature (37 °C) dramatically decreased mutant capsid protein stability and particle assembly. Electron microscopy confirmed the presence of cytoplasmic nucleocapsids in mutant-infected cells cultured at the permissive temperature, but these nucleocapsids were not stable to sucrose gradient separation. In contrast, nucleocapsids isolated from mutant virus particles had similar stability to that of wildtype virus. Our data support a model in which cytoplasmic nucleocapsids go through a maturation step during packaging into virus particles. The insertion site lies in the interface between capsid proteins in the assembled nucleocapsid, suggesting the region where such a stabilizing transition occurs. - Highlights: • We characterize an alphavirus capsid insertion mutation. • These capsid mutants are highly temperature sensitive for growth. • The insertion affects nucleocapsid stability. • Results suggest that the nucleocapsid is stabilized during virus budding.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Effect of Multiple Cation Electrolyte Mixtures on Rechargeable Zn–MnO 2 Alkaline Battery

A Bi 2 O 3 in β-MnO 2 composite cathode material has been synthesized using a simple hydrothermal method and cycled in a mixed KOH–LiOH electrolyte with a range of concentrations. We show that, at a KOH:LiOH molar ratio of 1:3, both proton insertion and lithium insertion occur, allowing access to a higher fraction of the theoretical capacity of the MnO 2 while preventing the formation of ZnMn 2 O 4 . This enables a capacity of 360 mAh/g for over 60 cycles, with cycling limited more by anode properties than traditional cathodic failure mechanisms. The structural changes occurring during cycling are characterized using electron microscopy and in situ synchrotron energy-dispersive X-ray diffraction (EDXRD) techniques. This mixed electrolyte shows exceptional cyclability and capacity and can be used as a drop-in replacement for current alkaline batteries, potentially drastically improving their cycle life and creating a wide range of new applications for this energy storage technology.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Surface-Enhanced Separation of Water from Hydrocarbons: Potential Dewatering Membranes for the Catalytic Fast Pyrolysis of Pine Biomass

The impact of surface-selective coatings on water permeation through a membrane when exposed to catalytic fast pyrolysis (CFP) vapor products was studied by tailoring the surface properties of the membrane coating from superhydrophilic to superhydrophobic. Our approach used high-performance architectured surface-selective (HiPAS) membranes that were inserted after a CFP reactor. At this insertion point, the inner wall surface of a tubular membrane was exposed to a mixture of water and upgraded product vapors, including light gases and deoxygenated hydrocarbons. Under proper membrane operating conditions, a high selectivity for water over one-ring upgraded biomass pyrolysis hydrocarbons was observed as a result of a surface-enhanced capillary condensation process. Owing to this surface-enhanced effect, HiPAS membranes have the potential to enable high flux separations, suggesting that water can be selectively removed from the CFP product vapors.

09 BIOMASS FUELS↗
DOE OSTI2017

Synthesis and Reactivity of Palladium(II) Alkyl Complexes that Contain Phosphine-cyclopentanesulfonate Ligands

The synthesis of the phosphine-cyclopentanesulfonate pro-ligands Li/K[2-PPh 2 -cyclopentanesulfonate] (Li/K[2a]), Li/K[2-P(2-OMe-Ph) 2 -cyclopentanesulfonate] (Li/K[2b]), and H[2b], and the corresponding Pd(II) alkyl complexes (κ 2 - P , O -2a)PdMe(pyridine) (3a) and (κ 2 - P , O -2b)PdMe(pyridine) (3b) is described herein. The sulfonate-bridged base-free dimer {(2b)PdMe} 2 (4b) was synthesized by abstraction of pyridine from 3b using B(C 6 F 5 ) 3 . The borane-coordinated base-free dimer [{2b·B(C 6 F 5 ) 3 }PdMe] 2 (5b), in which B(C 6 F 5 ) 3 binds to a sulfonate oxygen, was prepared by addition of 1 equiv of B(C 6 F 5 ) 3 per Pd to 4b or addition of 2 equiv of B(C 6 F 5 ) 3 to 3b. Compounds 3b, 4b, and 5b polymerize ethylene with low activity (up to 210 kg mol –1 h –1 at 250 psi and 80 °C) to linear polyethylene ( M n = 1950–5250 Da) with predominantly internal olefin placements. 3b and 4b copolymerize ethylene with methyl acrylate to linear copolymers that contain up to 11.7 mol % methyl acrylate, which is incorporated as –CH 2 CH(CO 2 Me)CH 2 – (80%) in-chain units and –CH 2 CH(CO 2 Me)Me (8%) and –CH 2 CH=CH(CO 2 Me) (12%) chain-end units. 3b and 4b also copolymerize ethylene with vinyl fluoride to linear copolymers that contain up to 0.41 mol % vinyl fluoride, which is incorporated as –CH 2 CHFCH 2 – (~80%) in-chain units and –CH 2 CF 2 H (7%), –CH 2 CHFCH 3 (5%), and –CH 2 CH 2 F (8%) chain-end units. Complexes 3b and 4b are more stable and active in ethylene polymerization than analogous (PAr 2 - CH 2 CH 2 SO 3 )PdR catalysts, but are less active than analogous (PAr 2 - arene sulfonate)PdR catalysts. Low-temperature NMR studies show that 4b reacts with ethylene below -10 °C to form the ethylene adduct cis - P , R -(2b)PdMe(ethylene) (7b), which undergoes ethylene insertion at 5 °C. DFT calculations for a model (PMe 2 -cyclopentanesulfonate)Pd(Pr)(ethylene) species show that ethylene insertion proceeds by cis - P , R / trans - P , R isomerization followed by migratory insertion, and that the lower activity of 3b and 4b vis-à-vis analogous (PAr 2 -arenesulfonate)PdR catalysts results from a higher barrier for migratory insertion of the trans - P , R isomer.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Lithiation Thermodynamics and Kinetics of the TiO 2 (B) Nanoparticles

TiO2 (B) has attracted a lot of attention in recent years because it exhibits the largest capacity among all studied titania polymorphs with high rate performance for Li intercalation achieved when this material is nanostructured. However, due to the complex nature of its lithiation mechanism and practical challenges in probing Li local environments in nanostructured materials, a definitive understanding of the lithiation thermodynamics has yet to be established. A comprehensive mechanistic investigation of the TiO2 (B) nanoparticles is therefore presented using a combination of in situ / operando X-ray pair distribution function (PDF) and electrochemical techniques. The discharge begins with surface reactions involving surface hydroxyl groups. Such reactions contribute to the capacity loss and take place in parallel with Li insertion into the near-surface region of the nanoparticles. The Li bulk insertion starts with a single-phase reaction into the A2 site, a position adjacent to the b channel. A change of the Li diffusion pathway from that along this open channel to that along the c-direction is likely to occur at the composition of Li0.25TiO2 until Li0.5TiO2 is attained, leading to a two-step A2-site incorporation with one step kinetically distinct from the other. Subsequent Li insertion involves C’ site, a position situated inside the channel, and follows a rapid two-phase reaction to form Li0.75TiO2. Due to the high diffusion barrier associated with the further lithiation, Li insertion into the A1 site, another position adjacent to the channel neighboring the A2 sites, is kinetically restricted. It can be promoted by either nanostructuring or raising the operating temperature, the latter however triggering concurrent electrolyte decomposition giving rise to additional capacity loss. This study not only provides compelling experimental evidence for the unresolved reaction thermodynamics of nanoparticulate TiO2 (B), but also serves as a strong reference for future studies of the bulk phase, and for future calculations to study the kinetic properties of TiO2 (B).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Reverse Dual-Ion Battery via a ZnCl 2 Water-in-Salt Electrolyte

Dual-ion batteries are known for anion storage in the cathode coupled to cation incorporation in the anode. We flip the sequence of the anion/cation-storage chemistries of the anode and the cathode in dual-ion batteries (DIBs) by allowing the anode to take in anions and a cation-deficient cathode to host cations, thus operating as a reverse dual-ion battery (RDIB). The anion-insertion anode is a nano-composite having ferrocene encapsulated inside a micro-porous carbon, and the cathode is a Zn-insertion Prussian blue, Zn-3[Fe(CN)(6)](2). This unique battery configuration benefits from the usage of a 30 m ZnCl2 "water-in-salt" electrolyte. This electrolyte minimizes the dissolution of ferrocene; it raises the cation-insertion potential in the cathode, and it depresses the anion-insertion potential in the anode, thus widening the full cell's voltage by 0.35 V compared with a dilute ZnCl2 electrolyte. RDIBs provide a configuration-based solution to exploit the practicality of cation-deficient cathode materials in aqueous electrolytes.

25 ENERGY STORAGE↗
DOE OSTI2014

Replication Bypass of the trans-4-Hydroxynonenal-Derived (6S,8R,11S)-1,N[superscript 2]-Deoxyguanosine DNA Adduct by the Sulfolobus solfataricus DNA Polymerase IV

trans-4-Hydroxynonenal (HNE) is the major peroxidation product of {omega}-6 polyunsaturated fatty acids in vivo. Michael addition of the N{sub 2}-amino group of dGuo to HNE followed by ring closure of N1 onto the aldehyde results in four diastereomeric 1,N{sub 2}-dGuo (1,N{sub 2}-HNE-dGuo) adducts. The (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct was incorporated into the 18-mer templates 5'-d(TCATXGAATCCTTCCCCC)-3' and d(TCACXGAATCCTTCCCCC)-3', where X = (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct. These differed in the identity of the template 5'-neighbor base, which was either Thy or Cyt, respectively. Each of these templates was annealed with either a 13-mer primer 5'-d(GGGGGAAGGATTC)-3' or a 14-mer primer 5'-d(GGGGGAAGGATTCC)-3'. The addition of dNTPs to the 13-mer primer allowed analysis of dNTP insertion opposite to the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, whereas the 14-mer primer allowed analysis of dNTP extension past a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) belongs to the Y-family of error-prone polymerases. Replication bypass studies in vitro reveal that this polymerase inserted dNTPs opposite the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct in a sequence-specific manner. If the template 5'-neighbor base was dCyt, the polymerase inserted primarily dGTP, whereas if the template 5'-neighbor base was dThy, the polymerase inserted primarily dATP. The latter event would predict low levels of Gua {yields} Thy mutations during replication bypass when the template 5'-neighbor base is dThy. When presented with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, the polymerase conducted full-length primer extension. Structures for ternary (Dpo4-DNA-dNTP) complexes with all four template-primers were obtained. For the 18-mer:13-mer template-primers in which the polymerase was confronted with the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, the (6S,8R,11S)-1,N{sub 2}-dGuo lesion remained in the ring-closed conformation at the active site. The incoming dNTP, either dGTP or dATP, was positioned with Watson-Crick pairing opposite the template 5'-neighbor base, dCyt or dThy, respectively. In contrast, for the 18-mer:14-mer template-primers with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, ring opening of the adduct to the corresponding N{sub 2}-dGuo aldehyde species occurred. This allowed Watson-Crick base pairing at the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide

Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2’-deoxyguanosine found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate E. coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerase discriminates between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine (Cy) and 8-oxodGTP(syn) utilizes its Hoogsteen edge to base pair with adenine (Ad). Here in this paper we utilized time-lapse crystallography to follow 8-oxo-dGTP insertion opposite Ad or Cy with human DNA pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxodGTP utilizes charge modulation during insertion that can lead to a blocked DNA repair intermediate.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Reversible intercalation of methyl viologen as a dicationic charge carrier in aqueous batteries

The interactions among charge carriers and electrode structures represent one of the most important considerations in the search for new energy storage devices. Currently, ionic bonding dominates the battery chemistry. In this work we report the reversible insertion of a large molecular dication, methyl viologen, into the crystal structure of an aromatic solid electrode, 3,4,9,10-perylenetetracarboxylic dianhydride. This is the largest insertion charge carrier when non-solvated ever reported for batteries; surprisingly, the kinetic properties of the (de) insertion of methyl viologen are excellent with 60% of capacity retained when the current rate is increased from 100 mA g -1 to 2000 mA g -1 . Characterization reveals that the insertion of methyl viologen causes phase transformation of the organic host, and embodies guest-host chemical bonding. First-principles density functional theory calculations suggest strong guest-host interaction beyond the pure ionic bonding, where a large extent of covalency may exist. This study extends the boundary of battery chemistry to large molecular ions as charge carriers and also highlights the electrochemical assembly of a supramolecular system.

25 ENERGY STORAGE↗