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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 1,081 records · Page 60
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Analyses of Dose Rates for Second Inner Reflector Plug Replacement at Spallation Neutron Source

The Inner Reflector Plug (IRP) is a central component of the Spallation Neutron Source (SNS) target monolith, which houses the liquid mercury target and four liter-sized neutron moderator units. It is exposed to high-level radiation fields during routine operation and builds up significant activity. The IRP needs to be replaced due to moderator neutron poison and decoupler burn-out, which is used for shaping neutron pulses. The first IRP exchange took place in March 2018 and next one, which is IRP2, is planned to be replaced during the facility maintenance period in the end of December 2025, beginning of January 2026 calendar year. The replacement of IRP is a complex task due to its location in the area receiving high irradiation, being under significant amount of shielding, and size, which requires removal in segments. For planning the replacement workflow to help to reduce radiation exposure to workers dose rates for each stage of extraction/replacement operation are predicted.

42 ENGINEERING↗
DOE OSTI2026

Nanopore Readable Activity Probes for Ribosomal Inactivating Protein (RIP) Toxins

Ribosome inactivating proteins (RIPs) such as ricin and abrin depurinate an adenine base in the sarcin/ricin loop in the large ribosomal subunit, leading to inhibtion of protein synthesis and cell death. Here, we demonstrate that RIP toxin activity can be detected via nanopore-based DNA sequencing using synthetic oligonucleotide substrates. This is achieved by monitoring the mismatch proportion at the canonical target sequences incorporated into the synthetic substrate and determining the sequence length distribution throughout the entire substrate sequence. The mismatch proportion increases and sequence length distribution decreases with increasing toxin concentration for both ricin and abrin in buffer as well as in more complex backgrounds such as saliva and nasal secretions.

Turner, Matthew W [Pacific Northwest National Labo↗
DOE OSTI2025

Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens

Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops (the P-loop, Ω-loop, and newly designated B-loop) that surround the active site. While each of these loops is known to influence enzyme function, their coordinated roles have not been fully elucidated. To investigate the significance of their interplay, we compared the sequences and crystal structures of 40 DBLs from clinically relevant Gram-negative pathogens and performed molecular dynamics simulations on selected representatives. Combined structural and dynamical analyses revealed a strong correlation between B-loop architecture and carbapenemase activity in the pathogens Klebsiella and Acinetobacter, particularly regarding loop length and spatial organization. These findings emphasize the B-loop’s critical contribution, in concert with the P- and Ω-loops, in tuning active site versatility, substrate recognition, catalytic activity, and structural stability. A deeper understanding of how these motifs and loops govern DBL function may inform the development of novel antibiotics and inhibitors targeting this class of enzymes.

antibiotic resistance↗
DOE OSTI2023

Characterization of radiation damage effects in high-energy neutrino target graphite using low-energy ions

Exposure of graphite targets to high intensity proton beams at neutrino production facilities causes changes in the target material that can result in a shortened operation lifetime. The dominant factors in this process are currently thought to be mechanical in nature resulting primarily from microstructural effects that lead to thermal and structural changes in bulk material properties. As currently planned beam facilities with increased proton energy and intensity begin to come online it will be important to thoroughly understand these processes, and ideally to be able to predict the effects of new beam designs on target properties. Direct analysis of targets exposed to existing high-energy proton beams is complicated by several factors, such as very limited access to proton beam facilities, high associated costs, irradiation times on the order of months, and the resulting radioactivity of irradiated samples that requires special facilities for post-irradiation examination. Much of the existing literature concerning irradiation damage in graphite has been focused on the needs of the nuclear engineering community, however high-energy proton targets operate in a much different environment. In comparison to graphite irradiated in a nuclear reactor, graphite used in proton beam targets receives a higher dose rate, have greater gas production, and experience short irradiation pulses as opposed to continuous irradiation. Low-energy ion irradiation offers a method of inducing similar levels of radiation damage to high-energy protons while avoiding many of the difficulties and limitations associated with high-energy proton beams and the corresponding activated specimen testing. My research described in this thesis focused on investigating how low-energy ion irradiation could be used to induce the same or similar types of microstructural alteration and mechanical property degradation as that seen in high-energy neutrino production target graphites by varying damage le vels and irradiation temperatures prior to post-irradiation characterisation.

43 PARTICLE ACCELERATORS↗
DOE OSTI2023

Development and Porting of Nuclear Reactor Computational Models for the NRIC Virtual Test Bed in FY23

The U.S. DOE’s National Reactor Innovation Center (NRIC) hosts an open-source website and associated GitHub repository called the Virtual Test Bed (VTB) on which computational models for advanced reactors are documented and shared with the reactor community. In FY23 under the NRIC program, computational models for nuclear reactor analysis were developed and contributed to the VTB Github repository during FY23 by contributors at Argonne National Laboratory. Other models developed outside of NRIC were also ported to the VTB as part of this work, serving a broader mission to make computational reactor analysis models more widely available to the reactor community. The model development activities focused on demonstration of gas-cooled microreactor models including computational fluid dynamics simulations of flow through an industry-inspired air jacket design, and simulation of multiphysics transients for a gas-cooled microreactor assembly. Additionally, development of a molten salt reactor (led at Idaho National Laboratory) was supported through Argonne’s expertise in multigroup cross sections generation. Models for these two reactor types were targeted due to their relevancy to NRIC’s Demonstration of Microreactor Experiments (DOME) and Laboratory for Operation and Testing in the U.S. (LOTUS) physical test beds, which are slated to host microreactor and molten salt reactor experiments. The model porting activities consisted of developing detailed documentation for several physics models which originate from the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. We include only contributions from Argonne National Laboratory in this report.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2021

G protein nucleolar 3 promotes Non-Hodgkin lymphoma progression by activating the Wnt/β-catenin signaling pathway

G protein nucleolar 3 (GNL3), which acts as an oncoprotein in various carcinomas, is associated with tumor progression; however, little is known regarding GNL3 function in non-Hodgkin lymphoma (NHL). In this study, we first used in silico analysis to determine associations between GNL3 and diffuse large B-cell lymphoma (DLBCL). We then examined the effect of GNL3 on NHL progression, including cell proliferation, apoptosis, and cell cycle progression, and determined its underlying molecular mechanism using in vitro lymphoma cell lines and in vivo mouse xenograft models. We found that GNL3 mRNA levels were markedly higher in DLBCL tissues than in normal tissues, with these higher levels associated with poor prognosis. Additionally, GNL3 overexpression promoted NHL cell proliferation and cell cycle progression and reduced apoptosis in vitro, and enhanced tumorigenesis in an in vivo xenograft model. Moreover, we found that GNL3 upregulated the levels of Wnt/β-catenin signaling pathway-related factors and downstream target genes, whereas the opposite result was observed in GNL3-silenced cells. Furthermore, a rescue experiment using a Wnt/β-catenin inhibitor (XAV939) confirmed that GNL3 promotes NHL progression by activating the Wnt/β-catenin signaling pathway. These findings demonstrated that GNL3 functions as an oncogenic driver in NHL via the Wnt/β-catenin pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Degradation-Resistant Hypoxia Inducible Factor-2α in Murine Osteocytes Promotes a High Bone Mass Phenotype

Molecular oxygen levels vary during development and disease. Adaptations to decreased oxygen bioavailability (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are composed of an oxygen-dependent α subunit (HIF-α), of which there are two transcriptionally active isoforms (HIF-1α and HIF-2α), and a constitutively expressed β subunit (HIFβ). Under normoxic conditions, HIF-α is hydroxylated via prolyl hydroxylase domain (PHD) proteins and targeted for degradation via Von Hippel-Lindau (VHL). Under hypoxic conditions, hydroxylation via PHD is inhibited, allowing for HIF-α stabilization and induction of target transcriptional changes. Our previous studies showed that Vhl deletion in osteocytes (Dmp1-cre; Vhlf/f) resulted in HIF-α stabilization and generation of a high bone mass (HBM) phenotype. The skeletal impact of HIF-1α accumulation has been well characterized; however, the unique skeletal impacts of HIF-2α remain understudied. Because osteocytes orchestrate skeletal development and homeostasis, we investigated the role of osteocytic HIF-α isoforms in driving HBM phenotypes via osteocyte-specific loss-of-function and gain-of-function HIF-1α and HIF-2α mutations in C57BL/6 female mice. Deletion of Hif1a or Hif2a in osteocytes showed no effect on skeletal microarchitecture. Constitutively stable, degradation-resistant HIF-2α (HIF-2α cDR), but not HIF-1α cDR, generated dramatic increases in bone mass, enhanced osteoclast activity, and expansion of metaphyseal marrow stromal tissue at the expense of hematopoietic tissue. Our studies reveal a novel influence of osteocytic HIF-2α in driving HBM phenotypes that can potentially be harnessed pharmacologically to improve bone mass and reduce fracture risk.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Synthesis of Free-Standing Pd-Ni-P Metallic Glass Nanoparticles with Durable Medium-Range Ordered Structure for Enhanced Electrocatalytic Properties

Topologically disordered metallic glass nanoparticles (MGNPs) with highly active and tailorable surface chemistries have immense potential for functional uses. The synthesis of free-standing MGNPs is crucial and intensively pursued because their activity strongly depends on their exposed surfaces. Herein, a novel laser-evaporated inert-gas condensation method is designed and successfully developed for synthesizing free-standing MGNPs without substrates or capping agents, which is implemented via pulse laser-induced atomic vapor deposition under an inert helium atmosphere. In this way, the metallic atoms vaporized from the targets collide with helium atoms and then condense into short-range-order (SRO) clusters, which mutually assemble to form the MGNPs. Using this method, free-standing Pd 40 Ni 40 P 20 MGNPs with a spherical morphology are synthesized, which demonstrates satisfactory electrocatalytic activity and durability in oxygen reduction reactions. Moreover, local structure investigations using synchrotron pair distribution function techniques reveal the transformation of SRO cluster connection motifs of the MGNPs from face-sharing to edge-sharing modes during cyclic voltammetry cycles, which enhances the electrochemical stability by blocking crystallization. Further, this approach provides a general strategy for preparing free-standing MGNPs with high surface activities, which may have widespread functional applications

36 MATERIALS SCIENCE↗
DOE OSTI2021

Liquid Chromatography Coupled to Refractive Index or Mass Spectrometric Detection for Metabolite Profiling in Lysate-based Cell-free Systems

Engineering cellular metabolism for targeted biosynthesis can require extensive design-build-test-learn (DBTL) cycles as the engineer works around the cell's survival requirements. Alternatively, carrying out DBTL cycles in cell-free environments can accelerate this process and alleviate concerns with host compatibility. A promising approach to cell-free metabolic engineering (CFME) leverages metabolically active crude cell extracts as platforms for biomanufacturing and for rapidly discovering and prototyping modified proteins and pathways. Realizing these capabilities and optimizing CFME performance requires methods to characterize the metabolome of lysate-based cell-free platforms. That is, analytical tools are necessary for monitoring improvements in targeted metabolite conversions and in elucidating alterations to metabolite flux when manipulating lysate metabolism. In this work, metabolite analyses using high-performance liquid chromatography (HPLC) coupled with either optical or mass spectrometric detection were applied to characterize metabolite production and flux in E. coli S30 lysates. Specifically, this report describes the preparation of samples from CFME lysates for HPLC analyses using refractive index detection (RID) to quantify the generation of central metabolic intermediates and by-products in the conversion of low-cost substrates (i.e., glucose) to various high-value products. The analysis of metabolite conversion in CFME reactions fed with 13 C-labeled glucose through reversed-phase liquid chromatography coupled to tandem mass spectrometry (MS/MS), a powerful tool for characterizing specific metabolite yields and lysate metabolic flux from starting materials, is also presented. Altogether, applying these analytical methods to CFME lysate metabolism enables the advancement of these systems as alternative platforms for executing faster or novel metabolic engineering tasks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Data for Genetic Variation in Zea mays Influences Microbial Nitrification and DeNitrification in Conventional Agroecosystems

Nitrogenous fertilizers provide a short-lived benefit to crops in agroecosystems, but stimulate nitrification and denitrification, processes that result in nitrate pollution, N2O production, and reduced soil fertility. Recent advances in plant microbiome science suggest that genetic variation in plants can modulate the composition and activity of rhizosphere N-cycling microorganisms. Here we attempted to determine whether genetic variation exists in Zea mays for the ability to influence the rhizosphere nitrifier and denitrifier microbiome under “real-world” conventional agricultural conditions. To capture an extensive amount of genetic diversity within maize we grew and sampled the rhizosphere microbiome of a diversity panel of germplasm that included ex-PVP inbreds ( Z. mays ssp. mays ), ex-PVP hybrids ( Z. mays ssp. may s), and teosinte ( Z. mays ssp. mexicana and Z. mays ssp. parviglumis ). From these samples, we characterized the microbiome, a suite of microbial genes involved in nitrification and denitrification and carried out N-cycling potential assays. Here we are showing that populations/genotypes of a single species can vary in their ecological interaction with denitrifers and nitrifers. Some hybrid and teosinte genotypes supported microbial communities with lower potential nitrification and potential denitrification activity in the rhizosphere, while inbred genotypes stimulated/did not inhibit these N-cycling activities. These potential differences translated to functional differences in N2O fluxes, with teosinte plots producing less GHG than maize plots. Taken together, these results suggest that Zea genetic variation can lead to changes in N-cycling processes that result in N leaching and N2O production, and thereby are selectable targets for crop improvement. Understanding the underlying genetic variation contributing to belowground microbiome N-cycling into our conventional agricultural system could be useful for sustainability.

Nitrogen↗
DOE OSTI2023

Materials Design Directions for Solar Thermochemical Water Splitting

The sustainable, economical production of molecular hydrogen is a crucial component of a net zero-greenhouse-gas-emissions future. Solar thermochemical water splitting (STWS) offers a renewable route to hydrogen with the potential to help decarbonize several industries, including transportation, manufacturing, mining, metals processing, and electricity generation, as well as provide sustainable hydrogen as a chemical feedstock. STWS uses high temperatures generated from concentrated sunlight or other sustainable means for high-temperature heat to produce hydrogen and oxygen from steam. For example, in its simplest form of a two-step thermochemical cycle, a redox-active metal oxide is heated to ≈1700-2000 K, driving off molecular oxygen while producing oxygen vacancies in the material. The reduced metal oxide then cools (ideally with the extracted heat recuperated for re-use) and, in a separate step, comes into contact with steam, which reacts with oxygen vacancies to produce molecular hydrogen while recovering the original state of the metal oxide. Despite its promising use of the entire solar spectrum to split water thermochemically, the current estimated cost of hydrogen produced via STWS is ≈4-6× the U.S. Department of Energy (DOE) Hydrogen Shot target value of $1/kg. One contributing approach to bridging this cost gap is the design of new materials with improved thermodynamic properties to enable higher efficiencies. The state-of-the-art (SOA) redox-active metal oxide for STWS is ceria (CeO 2 ), due to its close to optimal, although too high, oxygen vacancy formation enthalpy and large configurational and electronic entropy of reduction. However, ceria requires high operating temperatures and its efficiency is insufficient. Therefore, efforts to increase the efficiency of STWS cycles have focused on further optimizing oxygen vacancy formation enthalpies and augmenting the reduction entropy via substitution or doping and materials discovery schemes. Examples of the latter include the perovskites BaCe 0.25 Mn 0.75 O 3 and (Ca,Ce)(Ti,Mn)O 3 . These efforts and others have revealed intuitive chemical principles for the efficient and systematic design of more effective materials, such as the strong correlation between the enthalpies of crystal bond dissociation and solid-state cation reduction with the enthalpy of oxygen vacancy formation, as well as configurational entropy augmentation via the coexistence of two or more redox-active cation sublattices. The purpose of this chapter is to prepare the reader with an up-to-date account of STWS redox-active materials, both the SOA and promising newcomers, as well as to provide chemically intuitive strategies for improving their cycle efficiencies through materials design – in conjunction with ongoing efforts in reactor engineering and gas separations – to reach the cost points for commercial viability. First, we will introduce the thermodynamics of STWS using a two-step, metal-oxide, thermochemical cycle with economics in mind. We also will compare the pros and cons of processes that do or do not involve phase changes. Second, we will describe the qualities that make ceria the SOA STWS redox-active material, as well as its limitations. Third, we will survey some of the most promising candidates to date in the search for materials to supplant ceria, emphasizing the post-ternary, metal-oxide-perovskite alloys. Lastly, we will enumerate and discuss the following materials design directions for STWS redox-active materials: crystal reduction potentials as a proxy for oxygen vacancy formation enthalpies, engineering the electronic and configurational entropy of reduction via f-shells and simultaneous redox, and vetting materials stability via temperature-dependent phase diagrams and melting-point prediction.

08 HYDROGEN↗
DOE OSTI2022

Redshift evolution of the H I detection rate in radio-loud active galactic nuclei

We present a search for associated H I 21 cm absorption in a sample of 29 radio-loud active galactic nuclei (AGNs) at 0.7 < z < 1, carried out with the upgraded Giant Metrewave Radio Telescope. We detect H I 21 cm absorption against none of our target AGNs, obtaining 3σ upper limits to the optical depth of ≲1% per 50 km s –1 channel. The radio luminosity of our sources is lower than that of most AGNs searched for H I 21 cm absorption at similar redshifts in the literature, and, for all targets except two, the UV luminosity is below the threshold 10 23 W Hz –1 , above which the H I in the AGN environment has been suggested to be completely ionised. We stacked the H I 21 cm spectra to obtain a more stringent limit of ≈0.17% per 50 km s –1 channel on the average H I 21 cm optical depth of the sample. Furthermore, the sample is dominated by extended radio sources, 24 of which are extended on scales of tens of kiloparsecs. Including similar extended sources at 0.7 < z < 1.0 from the literature, and comparing with a low-z sample of extended radio sources, we find statistically significant (≈3σ) evidence that the strength of H I 21 cm absorption towards extended radio sources is weaker at 0.7 < z < 1.0 than at z < 0.25, with a lower detection rate of H I 21 cm absorption at 0.7 < z < 1.0. Redshift evolution in the physical conditions of H I is the likely cause of the weaker associated H I 21 cm absorption at high redshifts, due to either a low H I column density or a high spin temperature in high-z AGN environments.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

Two novel fish paralogs provide insights into the Rid family of imine deaminases active in pre-empting enamine/imine metabolic damage

Reactive Intermediate Deaminase (Rid) protein superfamily includes eight families among which the RidA is conserved in all domains of life. RidA proteins accelerate the deamination of the reactive 2-aminoacrylate (2AA), an enamine produced by some pyridoxal phosphate (PLP)-dependent enzymes. 2AA accumulation inhibits target enzymes with a detrimental impact on fitness. As a consequence of whole genome duplication, teleost fish have two ridA paralogs, while other extant vertebrates contain a single-copy gene. We investigated the biochemical properties of the products of two paralogs, identified in Salmo salar. Ss RidA-1 and Ss RidA-2 complemented the growth defect of a Salmonella enterica ridA mutant, an in vivo model of 2AA stress. In vitro, both proteins hydrolyzed 2-imino acids (IA) to keto-acids and ammonia. Ss RidA-1 was active on IA derived from nonpolar amino acids and poorly active or inactive on IA derived from other amino acids tested. In contrast, SsRidA-2 had a generally low catalytic efficiency, but showed a relatively higher activity with IA derived from L-Glu and aromatic amino acids. The crystal structures of Ss RidA-1 and Ss RidA-2 provided hints of the remarkably different conformational stability and substrate specificity. Overall, Ss RidA-1 is similar to the mammalian orthologs whereas SsRidA-2 displays unique properties likely generated by functional specialization of a duplicated ancestral gene.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling

Background:: The fibroblast growth factor (FGF) family is comprised of 23 highly regulatedmonomeric proteins that regulate a plethora of developmental and pathophysiological processes,including tissue repair, wound healing, angiogenesis, and embryonic development. Binding ofFGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan,heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediateinduction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, andSTAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification,FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions.Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis,and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiologicalchanges. Objective:: This comprehensive review will discuss the biology, chemistry, and functions of FGFs,and its current applications toward wound healing, diabetes, repair and regeneration of tissues, andfatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFRand aid in mitigating various disorders, such as cancer, are also discussed in detail. Conclusion:: Inhibitors of FGFR signaling are promising drugs in the treatment of several types ofcancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activationof other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activityon FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFRtargeting therapies is the recent focus of several preclinical and clinical studies.

Pharmacology & Pharmacy↗
DOE OSTI2024

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Global characterization of a laser-generated neutron source

Laser-driven neutron sources are routinely produced by the interaction of laser-accelerated protons with a converter. They present complementary characteristics to those of conventional accelerator-based neutron sources (e.g. short pulse durations, enabling novel applications like radiography). We present here results from an experiment aimed at performing a global characterization of the neutrons produced using the Titan laser at the Jupiter Laser Facility (Livermore, USA), where protons were accelerated from 23 $\mathrm {\mu }$ m thick plastic targets and directed onto a LiF converter to produce neutrons. For this purpose, several diagnostics were used to measure these neutron emissions, such as CR-39, activation foils, time-of-flight detectors and direct measurement of $^7{\rm Be}$ residual activity in the LiF converters. The use of these different, independently operating diagnostics enables comparison of the various measurements performed to provide a robust characterization. These measurements led to a neutron yield of $2.0\times 10^{9}$ neutrons per shot with a modest angular dependence, close to that simulated.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2020

Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate

SETD2 catalyzes methylation at lysine 36 of histone H3 and it has many disease connections. We investigated the substrate sequence specificity of SETD2 and identified nine additional peptide and one protein (FBN1) substrates. Our data showed that SETD2 strongly prefers amino acids different from those in the H3K36 sequence at several positions of its specificity profile. Based on this, we designed an optimized super-substrate containing four amino acid exchanges and show by quantitative methylation assays with SETD2 that the super-substrate peptide is methylated about 290-fold more efficiently than the H3K36 peptide. Protein methylation studies confirmed very strong SETD2 methylation of the super-substrate in vitro and in cells. We solved the structure of SETD2 with bound super-substrate peptide containing a target lysine to methionine mutation, which revealed better interactions involving three of the substituted residues. Our data illustrate that substrate sequence design can strongly increase the activity of protein lysine methyltransferases.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Contrasting the characteristics of atmospheric pressure plasma jets operated with single and double dielectric material: physicochemical characteristics and application to bacterial killing

Abstract This study reports an experimental comparison of two types of atmospheric pressure plasma jets in terms of their fundamental plasma characteristics and efficacy in bacterial sterilization. The plasma jets are fabricated by inserting a high voltage electrode inside a one-end closed (double DBD plasma jet) or both ends open (single DBD plasma jet) quartz tubes which are further enclosed inside a second quartz tube containing a ground electrode. Both plasma jets are operated in contact with water surface by using a unipolar pulsed DC power supply with helium as the working gas. Results from electrical and time-resolved imaging show that the single DBD configuration induces 3–4 times higher accumulation of charges onto the water surface with significantly faster propagation of plasma bullets. These results are accompanied by the higher discharge intensity as well as stronger emissions from short-lived reactive species which were analyzed through optical emission spectroscopy at the plasma-water interface. The rotational temperature for the single DBD configuration was observed to be higher making it unsafe for direct treatments of sensitive biological targets. These characteristics of the single DBD configuration result in the production of more than two times higher concentration of H 2 O 2 in plasma activated water. Shielding of the HV electrode reduces the plasma potential which in turn reduces the electric field & electron energy at the plasma-water interface. The reduced electric field for the double DBD configuration was lower by ≈463 Td than the single DBD configuration. The bactericidal efficacy of the two configurations of the plasma jets were tested against Escherichia coli , a well studied Gram-negative bacterium that can be commensal and pathogenic in human body. Our results demonstrate that although single DBD plasma jet result in stronger antibacterial effects, the double DBD configuration could be safer.

Physics↗