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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 OSTI2020

Delayed fluorescence from a zirconium(iv) photosensitizer with ligand-to-metal charge-transfer excited states

Advances in chemical control of the photophysical properties of transition-metal complexes are revolutionizing a wide range of technologies, particularly photocatalysis and light-emitting diodes, but they rely heavily on molecules containing precious metals such as ruthenium and iridium. While the application of earth-abundant ‘early’ transition metals in photosensitizers is clearly advantageous, a detailed understanding of excited states with ligand-to-metal charge transfer (LMCT) character is paramount to account for their distinct electron configurations. Here we report an air- and moisture-stable, visible lightabsorbing Zr(iv) photosensitizer, Zr( Mes PDP Ph ) 2 , where [ Mes PDP Ph ] 2- is the doubly deprotonated form of [2,6-bis(5-(2,4,6- trimethylphenyl)-3-phenyl-1H-pyrrol-2-yl)pyridine]. This molecule has an exceptionally long-lived triplet LMCT excited state (τ = 350 μs), featuring highly efficient photoluminescence emission (Ф = 0.45) due to thermally activated delayed fluorescence emanating from the higher-lying singlet configuration with significant LMCT contributions. Zr( Mes PDP Ph ) 2 engages in numerous photoredox catalytic processes and triplet energy transfer. Our exploration offers a blueprint for future photosensitizer development featuring early transition metals and excited states with significant LMCT contributions.

14 SOLAR ENERGY↗
DOE OSTI2023

Isolation, bonding and reactivity of a monomeric stibine oxide

Abstract In contrast to phosphine oxides and arsine oxides, which are common and exist as stable monomeric species featuring the corresponding pnictoryl functional group (Pn=O/Pn + –O − ; Pn = P, As), stibine oxides are generally polymeric, and the properties of the unperturbed stiboryl group (Sb=O/Sb + –O − ) remain unexplored. We now report the isolation of the monomeric stibine oxide, Dipp 3 SbO (where Dipp = 2,6-diisopropylphenyl). Spectroscopic, crystallographic and computational studies provide insight into the nature of the Sb=O/Sb + –O − bond. Moreover, isolation of Dipp 3 SbO allows the chemistry of the stiboryl group to be explored. Here we show that Dipp 3 SbO can act as a Brønsted base, a hydrogen-bond acceptor and a transition-metal ligand, in addition engaging in 1,2-addition, O-for-F 2 exchange and O-atom transfer. In all cases, the reactivity of Dipp 3 SbO differed from that of the lighter congeners Dipp 3 AsO and Dipp 3 PO.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Tackling Grand Challenges in Wind Energy through a Socio-Technical Perspective

Wind power has an important role to play in tackling climate change. Key challenges in wind energy science and innovation must be overcome to increase the penetration and capability of this technology. However, the success of these efforts heavily depends on how society engages with the development of wind power infrastructure. Consequently, grand challenges exist in both technical and social domains, yet little research has made substantial efforts in connecting them. Here we review the social science and humanities literature on wind energy to illustrate the social dimensions of previously identified technical challenges. We suggest that a socio-technical lens enables an interdisciplinary approach to overcome the prevalent tendency of silo thinking in wind energy research and use it to explore socio-technical grand challenges related to the design, planning, development, operational and end-of-life phases of wind energy. Finally, we provide an outlook for research, practice and innovation, including an interdisciplinary and socio-technical research agenda for wind energy science, renewable energy developments and science policy in general.

end-of-life↗
DOE OSTI2023

Viruses interact with hosts that span distantly related microbial domains in dense hydrothermal mats

Abstract Many microbes in nature reside in dense, metabolically interdependent communities. We investigated the nature and extent of microbe-virus interactions in relation to microbial density and syntrophy by examining microbe-virus interactions in a biomass dense, deep-sea hydrothermal mat. Using metagenomic sequencing, we find numerous instances where phylogenetically distant (up to domain level) microbes encode CRISPR-based immunity against the same viruses in the mat. Evidence of viral interactions with hosts cross-cutting microbial domains is particularly striking between known syntrophic partners, for example those engaged in anaerobic methanotrophy. These patterns are corroborated by proximity-ligation-based (Hi-C) inference. Surveys of public datasets reveal additional viruses interacting with hosts across domains in diverse ecosystems known to harbour syntrophic biofilms. We propose that the entry of viral particles and/or DNA to non-primary host cells may be a common phenomenon in densely populated ecosystems, with eco-evolutionary implications for syntrophic microbes and CRISPR-mediated inter-population augmentation of resilience against viruses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Prospects and challenges for nitrogen-atom transfer catalysis

Incorporation of nitrogen-based functional groups can profoundly impact the chemical and physical properties of organic small molecules. One-step conversion of C–H bonds to C–N bonds via C–H amination promises to streamline the synthesis of nitrogen-containing compounds. In pursuit of this promise, nitrogen-group transfer (NGT) from metal nitrenes (i.e., ligand supported M–NR complexes) has been the focus of intense research and development. In contrast, potentially complementary nitrogen-atom transfer (NAT) chemistry, in which a terminal metal nitride (i.e., ligand-supported M–N complex) engages with a C–H bond, is undeveloped. While the earliest examples of stoichiometric NAT chemistry were reported 25 years ago, catalytic protocols are only now beginning to emerge. Furthermore, we summarize the current state-of-the-art in NAT chemistry and discuss opportunities and challenges for the development of NAT catalysis as a platform for incorporation of nitrogen into organic small molecules. Specifically, we 1) highlight the synthetic complementarity of NGT and NAT chemistry, 2) discuss critical aspects of nitride electronic structure that dictate the philicity of supported metal atom, 3) examine the characteristic reactivity of metal nitrides towards substrate functionalization reactions, and 4) present emerging strategies and remaining obstacles to harnessing NAT for selective, catalytic nitrogenation of unfunctionalized organic small molecules.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Compression of curium pyrrolidine-dithiocarbamate enhances covalency

Curium is unique in the actinide series because its half-filled 5f 7 shell has lower energy than other 5f n configurations, rendering it both redox-inactive and resistant to forming chemical bonds that engage the 5f shell. This is even more pronounced in gadolinium, curium’s lanthanide analogue, owing to the contraction of the 4f orbitals with respect to the 5f orbitals. However, at high pressures metallic curium undergoes a transition from localized to itinerant 5f electrons. This transition is accompanied by a crystal structure dictated by the magnetic interactions between curium atoms. Therefore, the question arises of whether the frontier metal orbitals in curium(III)–ligand interactions can also be modified by applying pressure, and thus be induced to form metal–ligand bonds with a degree of covalency. Here we report experimental and computational evidence for changes in the relative roles of the 5f/6d orbitals in curium–sulfur bonds in [Cm(pydtc) 4 ] – (pydtc, pyrrolidinedithiocarbamate) at high pressures (up to 11 gigapascals). We compare these results to the spectra of [Nd(pydtc) 4 ] – and of a Cm(III) mellitate that possesses only curium–oxygen bonds. Compared with the changes observed in the [Cm(pydtc) 4 ] – spectra, we observe smaller changes in the f–f transitions in the [Nd(pydtc) 4 ] – absorption spectrum and in the f–f emission spectrum of the Cm(III) mellitate upon pressurization, which are related to the smaller perturbation of the nature of their bonds. These results reveal that the metal orbital contributions to the curium–sulfur bonds are considerably enhanced at high pressures and that the 5f orbital involvement doubles between 0 and 11 gigapascal. Furthermore, our work implies that covalency in actinides is complex even when dealing with the same ion, but it could guide the selection of ligands to study the effect of pressure on actinide compounds.

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

Isolation and characterization of a californium metallocene

Californium (Cf) is currently the heaviest element accessible above microgram quantities. Cf isotopes impose severe experimental challenges due to their scarcity and radiological hazards. Consequently, chemical secrets ranging from the accessibility of 5f/6d valence orbitals to engage in bonding, the role of spin–orbit coupling in electronic structure, and reactivity patterns compared to other f elements, remain locked. Organometallic molecules were foundational in elucidating periodicity and bonding trends across the periodic table, with a twenty-first-century renaissance of organometallic thorium (Th) through plutonium (Pu) chemistry, and to a smaller extent americium (Am), transforming chemical understanding. Yet, analogous curium (Cm) to Cf chemistry has lain dormant since the 1970s. Here, we revive air-/moisture-sensitive Cf chemistry through the synthesis and characterization of [Cf(C 5 Me 4 H) 2 Cl 2 K(OEt 2 )] n from two milligrams of 249 Cf. This bent metallocene motif, not previously structurally authenticated beyond uranium (U), contains the first crystallographically characterized Cf–C bond. Analysis suggests the Cf–C bond is largely ionic with a small covalent contribution. Lowered Cf 5f orbital energy versus dysprosium (Dy) 4f in the colourless, isoelectronic and isostructural [Dy(C 5 Me 4 H) 2 Cl 2 K(OEt 2 )] n results in an orange Cf compound, contrasting with the light-green colour typically associated with Cf compounds.

Chemical bonding↗
DOE OSTI2022

Structural basis for SHOC2 modulation of RAS signalling

The RAS–RAF pathway is one of the most commonly dysregulated in human cancers. Despite decades of study, understanding of the molecular mechanisms underlying dimerization and activation of the kinase RAF remains limited. Recent structures of inactive RAF monomer and active RAF dimer bound to 14-3-3 have revealed the mechanisms by which 14-3-3 stabilizes both RAF conformations via specific phosphoserine residues. Prior to RAF dimerization, the protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate the N-terminal phosphoserine (NTpS) of RAF to relieve inhibition by 14-3-3, although PP1C in isolation lacks intrinsic substrate selectivity. SHOC2 is as an essential scaffolding protein that engages both PP1C and RAS to dephosphorylate RAF NTpS, but the structure of SHOC2 and the architecture of the presumptive SHOC2–PP1C–RAS complex remain unknown. Here we present a cryo-electron microscopy structure of the SHOC2–PP1C–MRAS complex to an overall resolution of 3Å, revealing a tripartite molecular architecture in which a crescent-shaped SHOC2 acts as a cradle and brings together PP1C and MRAS. Our work demonstrates the GTP dependence of multiple RAS isoforms for complex formation, delineates the RAS-isoform preference for complex assembly, and uncovers how the SHOC2 scaffold and RAS collectively drive specificity of PP1C for RAF NTpS. Our data indicate that disease-relevant mutations affect complex assembly, reveal the simultaneous requirement of two RAS molecules for RAF activation, and establish rational avenues for discovery of new classes of inhibitors to target this pathway.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Cryo-EM structures reveal native GABA A receptor assemblies and pharmacology

Type A γ-aminobutyric acid receptors (GABA A Rs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants. However, our understanding of GABA A R pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABA A R assemblies containing the widely expressed α1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron microscopy (cryo-EM) analysis and single-molecule photobleaching experiments, we uncover three major structural populations in the brain: the canonical α1β2γ2 receptor containing two α1 subunits, and two assemblies containing one α1 and either an α2 or α3 subunit, in which the single α1-containing receptors feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, APG is bound at the transmembrane α/β subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABA A Rs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify the ion channel pore and the binding sites for GABA and insomnia medications. Our data reveal the major α1-containing GABA A R assemblies, bound with endogenous neurosteroid, thus defining a structural landscape from which subtype-specific drugs can be developed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Template and target-site recognition by human LINE-1 in retrotransposition

The long interspersed element-1 (LINE-1, hereafter L1) retrotransposon has generated nearly one-third of the human genome and serves as an active source of genetic diversity and human disease. L1 spreads through a mechanism termed target-primed reverse transcription, in which the encoded enzyme (ORF2p) nicks the target DNA to prime reverse transcription of its own or non-self RNAs. Here we purified full-length L1 ORF2p and biochemically reconstituted robust target-primed reverse transcription with template RNA and target-site DNA. We report cryo-electron microscopy structures of the complete human L1 ORF2p bound to structured template RNAs and initiating cDNA synthesis. The template polyadenosine tract is recognized in a sequence-specific manner by five distinct domains. Among them, an RNA-binding domain bends the template backbone to allow engagement of an RNA hairpin stem with the L1 ORF2p C-terminal segment. Moreover, structure and biochemical reconstitutions demonstrate an unexpected target-site requirement: L1 ORF2p relies on upstream single-stranded DNA to position the adjacent duplex in the endonuclease active site for nicking of the longer DNA strand, with a single nick generating a staggered DNA break. Our research provides insights into the mechanism of ongoing transposition in the human genome and informs the engineering of retrotransposon proteins for gene therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A small molecule inhibitor prevents gut bacterial genotoxin production

Abstract The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.

Biochemistry & Molecular Biology↗
DOE OSTI2022

Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA

Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered driver oncogenes, generates an immunogenic public NeoAg. Using this strategy, we developed a panel of TCRs that recognize an endogenously processed neopeptide encompassing a common PIK3CA hotspot mutation restricted by the prevalent human leukocyte antigen (HLA)-A*03:01 allele. Mechanistically, immunogenicity to this public NeoAg arises from enhanced neopeptide/HLA complex stability caused by a preferred HLA anchor substitution. Structural studies indicated that the HLA-bound neopeptide presents a comparatively ‘featureless’ surface dominated by the peptide’s backbone. To bind this epitope with high specificity and affinity, we discovered that a lead TCR clinical candidate engages the neopeptide through an extended interface facilitated by an unusually long CDR3β loop. In patients with diverse malignancies, we observed NeoAg clonal conservation and spontaneous immunogenicity to the neoepitope. Finally, adoptive transfer of TCR-engineered T cells led to tumor regression in vivo in mice bearing PIK3CA-mutant tumors but not wild-type PIK3CA tumors. Together, these findings establish the immunogenicity and therapeutic potential of a mutant PIK3CA-derived public NeoAg.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Critical Assessment of Metagenome Interpretation: the second round of challenges

Abstract Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Control of transcription elongation and DNA repair by alarmone ppGpp

Second messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More recently, ppGpp has been implicated in coupling transcription and DNA repair; however, the mechanism of ppGpp engagement remained elusive. Here we present structural, biochemical and genetic evidence that ppGpp controls Escherichia coli RNA polymerase (RNAP) during elongation via a specific site that is nonfunctional during initiation. Structure-guided mutagenesis renders the elongation (but not initiation) complex unresponsive to ppGpp and increases bacterial sensitivity to genotoxic agents and ultraviolet radiation. Thus, ppGpp binds RNAP at sites with distinct functions in initiation and elongation, with the latter being important for promoting DNA repair. Our data provide insights on the molecular mechanism of ppGpp-mediated adaptation during stress, and further highlight the intricate relationships between genome stability, stress responses and transcription.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural basis of sequence-specific cytosine deamination by double-stranded DNA deaminase toxin DddA

The interbacterial deaminase toxin DddA catalyzes cytosine-to-uracil conversion in double-stranded (ds) DNA and enables CRISPR-free mitochondrial base editing, but the molecular mechanisms underlying its unique substrate selectivity have remained elusive. Here, we report crystal structures of DddA bound to a dsDNA substrate containing the 5'-TC target motif. These structures show that DddA binds to the minor groove of a sharply bent dsDNA and engages the target cytosine extruded from the double helix. DddA Phe1375 intercalates in dsDNA and displaces the 5' (-1) thymine, which in turn replaces the target (0) cytosine and forms a noncanonical T–G base pair with the juxtaposed guanine. This tandem displacement mechanism allows DddA to locate a target cytosine without flipping it into the active site. Biochemical experiments demonstrate that DNA base mismatches enhance the DddA deaminase activity and relax its sequence selectivity. On the basis of the structural information, we further identified DddA mutants that exhibit attenuated activity or altered substrate preference. Our studies may help design new tools useful in genome editing or other applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The CNK–HYP scaffolding complex promotes RAF activation by enhancing KSR–MEK interaction

The RAS–MAPK pathway regulates cell proliferation, differentiation and survival, and its dysregulation is associated with cancer development. The pathway minimally comprises the small GTPase RAS and the kinases RAF, MEK and ERK. Activation of RAF by RAS is notoriously intricate and remains only partially understood. There are three RAF isoforms in mammals (ARAF, BRAF and CRAF) and two related pseudokinases (KSR1 and KSR2). RAS-mediated activation of RAF depends on an allosteric mechanism driven by the dimerization of its kinase domain. Recent work on human RAFs showed that MEK binding to KSR1 promotes KSR1–BRAF heterodimerization, which leads to the phosphorylation of free MEK molecules by BRAF. Similar findings were made with the single Drosophila RAF homolog. Here we show that the fly scaffold proteins CNK and HYP stabilize the KSR–MEK interaction, which in turn enhances RAF–KSR heterodimerization and RAF activation. The cryogenic electron microscopy structure of the minimal KSR–MEK–CNK–HYP complex reveals a ring-like arrangement of the CNK–HYP complex allowing CNK to simultaneously engage KSR and MEK, thus stabilizing the binary interaction. Together, these results illuminate how CNK contributes to RAF activation by stimulating the allosteric function of KSR and highlight the diversity of mechanisms impacting RAF dimerization as well as the regulatory potential of the KSR–MEK interaction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Spatial and Temporal Characterization of Activity in Public Space, 2019–2020

The data reported here characterize spatial and temporal variation in the ratio of short-to-long-duration visits in public places (i.e., points of interest) in the United States for each week between January 2019 and December 2020. The underlying data on anonymized and aggregated foot traffic to public places is curated by SafeGraph, a geospatial data provider. In this work, we report the estimated number and duration of “short” (i.e., <4 hours) and “long” (i.e., >4 hours) visits to public places at the US census block group level. Long visits are shown to be a good proxy for workers based on formal economic data. We propose that short visits are more likely to represent nonobligate activities: people visiting a public place for leisure, shopping, entertainment, or civic or cultural engagement. Our work constructs a ratio of short to long visits, which can be used to inform population estimates for nonworker use of public space. These data may be useful for understanding how people’s use of public space has changed during the COVID-19 pandemic and, more generally, for understanding activity patterns in public.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2026

Heterogeneous estimations of non-pharmaceutical mitigation behavior during the COVID-19 pandemic

The COVID-19 pandemic highlighted the importance of human behavior in mitigating the spread of disease. Nonetheless, human behavior is often overlooked in models of disease spread, particularly by underutilizing real-world data. We address this by estimating probabilities that individuals engage in behaviors that influence SARS-CoV-2 transmission risk during the COVID-19 pandemic, between September 2020 and June 2022. These behaviors include wearing a mask, using public transportation, spending time with others, avoiding contact with others, and going to work. Our estimates account for the age and sex of individuals and are generated for every county in the United States. We utilized multiple open-source datasets and United States Census data to produce these estimates. Multiple datasets were used for validation, showing our estimates demonstrated comparable accuracy and robustness. Our estimates aid in understanding human behavior dynamics during the COVID-19 pandemic and could be used to inform monthly or longer-term behavior in simulations of COVID-19. Moreover, the methods presented can be applied to other behaviors and features for future simulations of infectious disease.

97 MATHEMATICS AND COMPUTING↗