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Results for “EXCLUSIVE INTERACTIONS”

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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Identification and interplay of sequence specific DNA binding proteins involved in regulation of human Pregnane and Xenobiotic Receptor gene

Pregnane and Xenobiotic Receptor (PXR), a member of nuclear receptor superfamily, acts as a ‘xenosensor’ in our body and modulates a network of genes involved in xenobiotic metabolism and elimination. Expression levels of PXR in certain metabolic disorders including cancer are reported to be altered and its induced expression is associated with the development of resistance towards chemotherapy and adverse drug–drug interactions. Though the transcriptional regulation of PXR target genes have been elucidated in significant details, the structure and functional control of PXR promoter itself remains inadequately explored. In this work, we identify a Composite Element (CE) located within the proximal PXR promoter region that consists of multiple overlapping cis-elements and demonstrated that CE interacts specifically with some critical nuclear proteins. Subsequent DNA-protein interaction studies revealed mutually exclusive interactions on CE occurring between Sp1 and two unidentified DNA binding proteins with molecular masses of 50 and 54 kDa. Here, we report the identification of 54 kDa CE binding protein as a heterogeneous nuclear ribonucleoprotein K (hnRNPK) and demonstrate the effect of hnRNP K and Sp1 on PXR promoter transcriptional activity. Overall, the study indicates that PXR gene is tightly regulated to maintain a low receptor level. - Highlights: • Cis-regulatory elements present in proximal promoter of PXR are identified. • A composite element (CE) region is involved in PXR gene regulation. • Trans-acting factors binding to CE are identified as Sp1 and hnRNPK. • Mutually exclusive interactions between hnRNPK and other CEBFs at CE are observed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Study of the Hyperon-Nucleon Interaction in Exclusive Λ Photoproduction off the Deuteron

The study of final-state interactions in exclusive hyperon photoproduction off the deuteron is a promising approach to extract information about the hyperon-nucleon (YN) interaction. First preliminary results on the azimuthal asymmetry ∑, as well as the polarization transfer coeffcients Ox, Oz, Cx, and Cz for the reaction γd → K+ Λn initiated with linearly and circularly polarized photon beam are presented. The data were taken with the CLAS detector in Hall B of Jefferson Lab during the E06-103 experiment. The large kinematic coverage of the CLAS, combined with the exceptionally high quality of the experimental data, allows identifying and selecting final-state interaction events to extract single- and double-polarization observables and their kinematical dependencies.

Zachariou, Nicholas↗
DOE OSTI2016

Studies of $\Lambda n$ interaction through polarization observables for final-state interactions in exclusive $\Lambda$ photoproduction off the deuteron

Theoretical studies suggest that experimental observables for hyperon production reactions can place stringent constraints on the free parameters of hyperon-nucleon potentials, which are critical for the understanding of hypernuclear matter and neutron stars. Here we present preliminary experimental results for the polarization observables S, Py, Ox, Oz, Cx, and Cz for final-state interactions (FSI) in exclusive L photoproduction off the deuteron. The observables were obtained from data collected during the E06-103 (g13) experiment with the CEBAF Large Acceptance Spectrometer (CLAS) in Hall B at Jefferson Lab. The g13 experiment ran with unpolarized deuteron target and circularly- and linearly-polarized photon beams with energies between 0.5 GeV and 2.5 GeV and collected about 51010 events with multiple charged particles in the final state. To select the reaction of interest, the K+ and the L decay products, a proton and a negative pion, were detected in the CLAS. The missing-mass technique was used to identify exclusive hyperon photoproduction events. Final-state interaction events were selected by requesting that the reconstructed neutron has a momentum larger than 200 MeV/c. The large statistics of E06-103 provided statistically meaningful FSI event samples, which allow for the extraction of one- and two-fold differential single- and double-polarization observables. Here we present preliminary results for a set of six observables for photon energies between 0.9 GeV and 2.3 GeV and for several kinematic variables in the Ln center-of-mass frame. Our results are the very first estimates of polarization observables for FSI in hyperon photoproduction and will be used to constrain the free parameters of hyperon-nucleon potentials.

Ilieva, Yordanka↗
DOE OSTI2023

Cryo-EM structure of adeno-associated virus 4 at 2.2 Å resolution

Adeno-associated virus (AAV) is the vector of choice for several approved gene-therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as serotypes), each with their own transfection characteristics. Here, a high-resolution cryo-electron microscopy structure (2.2 Å) of AAV serotype 4 (AAV4) is presented. The receptor responsible for transduction of the AAV4 clade of AAV viruses (including AAV11, AAV12 and AAVrh32.33) is unknown. Other AAVs interact with the same cell receptor, adeno-associated virus receptor (AAVR), in one of two different ways. AAV5-like viruses interact exclusively with the polycystic kidney disease-like 1 (PKD1) domain of AAVR, while most other AAVs interact primarily with the PKD2 domain. A comparison of the present AAV4 structure with prior corresponding structures of AAV5, AAV2 and AAV1 in complex with AAVR provides a foundation for understanding why the AAV4-like clade is unable to interact with either PKD1 or PKD2 of AAVR. The conformation of the AAV4 capsid in variable regions I, III, IV and V on the viral surface appears to be sufficiently different from AAV2 to ablate binding with PKD2. Differences between AAV4 and AAV5 in variable region VII appear to be sufficient to exclude binding with PKD1.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Crystal structure of an Escherichia coli Hfq Core (residues 2–69)–DNA complex reveals multifunctional nucleic acid binding sites

Hfq regulates bacterial gene expression post-transcriptionally by binding small RNAs and their target mRNAs, facilitating sRNA-mRNA annealing, typically resulting in translation inhibition and RNA turnover. Hfq is also found in the nucleoid and binds double-stranded (ds) DNA with a slight preference for A-tracts. Here, we present the crystal structure of the Escherichia coli Hfq Core bound to a 30 bp DNA, containing three 6 bp A-tracts. Although previously postulated to bind to the ‘distal’ face, three statistically disordered double stranded DNA molecules bind across the proximal face of the Hfq hexamer as parallel, straight rods with B-DNA like conformational properties. One DNA duplex spans the diameter of the hexamer and passes over the uridine-binding proximal-face pore, whereas the remaining DNA duplexes interact with the rims and serve as bridges between adjacent hexamers. Binding is sequence-independent with residues N13, R16, R17 and Q41 interacting exclusively with the DNA backbone. Atomic force microscopy data support the sequence-independent nature of the Hfq-DNA interaction and a role for Hfq in DNA compaction and nucleoid architecture. Our structure and nucleic acid-binding studies also provide insight into the mechanism of sequence-independent binding of Hfq to dsRNA stems, a function that is critical for proper riboregulation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

PE5–PPE4–EspG 3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems

Mycobacterium tuberculosis has evolved numerous type VII secretion (ESX) systems to secrete multiple factors important for both growth and virulence across their cell envelope. ESX-1, ESX-3, and ESX-5 systems have been shown to each secrete a distinct set of substrates, including PE and PPE families of proteins, named for conserved Pro-Glu and Pro-Pro-Glu motifs in their N termini. Proper secretion of the PE–PPE proteins requires the presence of EspG, with each system encoding its own unique copy. There is no cross-talk between any of the ESX systems, and how each EspG recognizes its subset of PE–PPE proteins is currently unknown. The only current structural characterization of PE–PPE–EspG heterotrimers is from the ESX-5 system. Here we present the crystal structure of the PE5 mt –PPE4 mt –EspG 3mm heterotrimer from the ESX-3 system. Our heterotrimer reveals that EspG 3mm interacts exclusively with PPE4 mt in a similar manner to EspG 5 , shielding the hydrophobic tip of PPE4 mt from solvent. The C-terminal helical domain of EspG 3mm is dynamic, alternating between “open” and “closed” forms, and this movement is likely functionally relevant in the unloading of PE–PPE heterodimers at the secretion machinery. In contrast to the previously solved ESX-5 heterotrimers, the PE–PPE heterodimer of our ESX-3 heterotrimer is interacting with its chaperone at a drastically different angle and presents different faces of the PPE protein to the chaperone. We conclude that the PPE–EspG interface from each ESX system has a unique shape complementarity that allows each EspG to discriminate among noncognate PE–PPE pairs.

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

Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes

Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively episomal state or integrated into the host chromosome and virions are continuously released without killing the host. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications, such as phage display, or because of their effect on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here, we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a machine learning approach leveraging a combination of marker gene and genome features, we identified 10,295 inovirus-like sequences from microbial genomes and metagenomes. Collectively, our results call for reclassification of the current Inoviridae family into a viral order including six distinct proposed families associated with nearly all bacterial phyla across virtually every ecosystem. Putative inoviruses were also detected in several archaeal genomes, suggesting that, collectively, members of this supergroup infect hosts across the domains Bacteria and Archaea. Finally, we identified an expansive diversity of inovirus-encoded toxin–antitoxin and gene expression modulation systems, alongside evidence of both synergistic (CRISPR evasion) and antagonistic (superinfection exclusion) interactions with co-infecting viruses, which we experimentally validated in a Pseudomonas model. Capturing this previously obscured component of the global virosphere may spark new avenues for microbial manipulation approaches and innovative biotechnological applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Thermodynamic stability and structural properties of cluster crystals formed by amphiphilic dendrimers

We pursue the goal of finding real-world examples of macromolecular aggregates that form cluster crystals, which have been predicted on the basis of coarse-grained, ultrasoft pair potentials belonging to a particular mathematical class [B. M. Mladek et al., Phys. Rev. Lett. 46, 045701 (2006)]. For this purpose, we examine in detail the phase behavior and structural properties of model amphiphilic dendrimers of the second generation by means of monomer-resolved computer simulations. On augmenting the density of these systems, a fluid comprised of clusters that contain several overlapping and penetrating macromolecules is spontaneously formed. Upon further compression of the system, a transition to multi-occupancy crystals takes place, the thermodynamic stability of which is demonstrated by means of free-energy calculations, and where the FCC is preferred over the BCC-phase. Contrary to predictions for coarse-grained theoretical models in which the particles interact exclusively by effective pair potentials, the internal degrees of freedom of these molecules cause the lattice constant to be density-dependent. Furthermore, the mechanical stability of monodisperse BCC and FCC cluster crystals is restricted to a bounded region in the plane of cluster occupation number versus density. The structural properties of the dendrimers in the dense crystals, including their overall sizes and the distribution of monomers are also thoroughly analyzed.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Construction of the optical part of a time-of-flight detector prototype for the AFP detector

We present the construction of the optical part of the ToF (time-of-flight) subdetector prototype for the AFP (ATLAS Forward Proton) detector. The ToF detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through it. Finally, the emitted Cherenkov photons are detected by a micro-channel plate multi-anode Photomultiplier Tube (MCP-PMT) and processed by fast electronics.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2018

Timing resolution studies of the optical part of the AFP Time-of-flight detector

We present results of the timing performance studies of the optical part and front-end electronics of the time-of-flight subdetector prototype for the ATLAS Forward Proton (AFP) detector obtained during the test campaigns at the CERN-SPS test-beam facility (120 GeV π + particles) in July 2016 and October 2016. The time-of-flight (ToF) detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for the measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through them. The emitted Cherenkov photons are detected by a multi-anode micro-channel plate photomultiplier tube (MCP-PMT) and processed by fast electronics.

47 OTHER INSTRUMENTATION↗
DOE OSTI2018

Characterization of Backgrounds for EXO

Neutrinos are fundamental particles that are all around us in nature. While neutrinos do not make up the building blocks of matter, they are an important byproduct of the fusion process that makes the sun burn. Because neutrinos are so light in mass, they almost exclusively interact with the weak force in nature. As such, they provide a unique probe for understanding the weak force. The heaviest mass of the neutrino is still so much lighter than all the other charged quarks and leptons that it hints at the possibility that their mass is produced by a different mechanism than the Higgs boson. How can we study these fleeting objects? This is the challenge for neutrino physicists, and we continue to push the limits of the experimental techniques further and further. Neutrinoless double beta decay is a unique probe of neutrinos that will attempt to answer the question of whether the neutrino is its own anti-particle (Majorana), what it's absolute mass is and if observed, we will see violation of lepton number which will lead the way to new physics. Discovering neutrinoless double beta decay will be exciting but still left to be answered will be what the mechanism is that causes the decay. Understanding this mechanism will also give us more insight into the weak force or new forces at work in the universe. The current experiments are attempting to measure the decay half-life at the level of 1025-1026 years. In order to do this (and better in the future), it is critical to eliminate as many radioactive background processes as possible by shielding from external radioactivity and reducing the internal radioactivity of the detector. This report discusses measurements performed to study potential backgrounds due to neutrons interacting with 136Xe that could affect experiments such as EXO-200 (Enriched Xenon Observatory - 200 kg) and nEXO (next Enriched Xenon Observatory) and KamLAND-Zen.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2026

Measurement of exclusive 𝜋 + -argon interactions using ProtoDUNE-SP

We present the measurement of 𝜋 + -argon inelastic cross sections using the ProtoDUNE single-phase liquid argon time projection chamber in the incident 𝜋 + kinetic energy range of 500–800 MeV in multiple exclusive channels (absorption, charge exchange, and the remaining inelastic interactions). The results of this analysis are important inputs to simulations of liquid argon neutrino experiments such as the Deep Underground Neutrino Experiment and the Short Baseline Neutrino program at Fermi National Accelerator Laboratory. They will be employed to improve the modeling of final state interactions within neutrino event generators used by these experiments, as well as the modeling of 𝜋 + -argon secondary interactions within the liquid argon. This is the first measurement of 𝜋 + -argon absorption at this kinetic energy range as well as the first ever measurement of 𝜋 + -argon charge exchange.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2022

First Measurement of Differential Charged Current Quasi-Elastic-Like $\nu_{\mu}$ Argon Scattering Cross Sections with the MicroBooNE Detector

Current and future generation neutrino oscillation experiments aim towards a high-precisionmeasurement of the oscillation parameters, which requires an unprecedented understanding ofneutrino-nucleus scattering. Charged-current quasi-elastic (CCQE) scattering is the process inwhich the neutrino produces a charged lepton and removes a single intact nucleon from the nu-cleus without producing any additional particles. For existing and forthcoming accelerator–based neutrino experiments, CCQE interactions are either the dominant process or part of the signal.MicroBooNE is the first liquid argon time projection chamber (LArTPC) commissioned as part ofthe Short Baseline Neutrino (SBN) program at Fermilab and its excellent particle reconstructioncapabilities allow the detection of neutrino interactions using exclusive final states, which will playa crucial role in the success of future kiloton LArTPC detectors such as DUNE. This talk willpresent the first measurement of exclusive νμ-Ar CCQE–like flux integrated total and differentialcross sections using single proton knock–out interactions recorded by the MicroBooNE LArTPCdetector, which has comparable acceptance to deuterium Bubble Chambers.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2015

Dna2 nuclease-helicase structure, mechanism and regulation by Rpa

The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5’ end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5’ but not 3’ end, explaining how Rpa regulates cleavage polarity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Virtuality Distributions and γγ * -> π 0 Transition at Handbag Level

We outline a new approach to transverse momentum dependence in hard processes using as an example the exclusive transition ${\gamma^{*}\gamma \to \pi^{0}}$ at the handbag level. We start with the coordinate representation for a matrix element ${\langle p |{\cal O}(0,z) |0 \rangle}$ of a bilocal operator ${{\cal O} (0,z)}$ describing a hadron with momentum p. Treated as a function of (pz) and z$^{2}$, it is parametrized through virtuality distribution amplitude (VDA) Φ (x, σ), with x being Fourier-conjugate to (pz) and σ Laplace-conjugate to z$^{2}$. For intervals with z$^{+}$ = 0, we introduce the transverse momentum distribution amplitude (TMDA) ${\Ψ (x,k_{\perp})}$ , and write it in terms of VDA Φ (x, σ). The results of covariant calculations, written in terms of Φ (x, σ) are converted into expressions involving ${\Ψ (x,k_{\perp})}$ . We propose simple models for soft VDAs/TMDAs, and use them for comparison of handbag results with experimental (BaBar and BELLE) data on the pion transition form factor.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2019

Rejecting cosmic background for exclusive charged current quasi elastic neutrino interaction studies with Liquid Argon TPCs; a case study with the MicroBooNE detector

Cosmic ray (CR) interactions can be a challenging source of background for neutrino oscillation and cross-section measurements in surface detectors. We present methods for CR rejection in measurements of charged-current quasielastic-like (CCQE-like) neutrino interactions, with a muon and a proton in the final state, measured using liquid argon time projection chambers (LArTPCs). Using a sample of cosmic data collected with the MicroBooNE detector, mixed with simulated neutrino scattering events, a set of event selection criteria is developed that produces an event sample with minimal contribution from CR background. Depending on the selection criteria used a purity between 50% and 80% can be achieved with a signal selection efficiency between 50% and 25%, with higher purity coming at the expense of lower efficiency. While using a specific dataset from the MicroBooNE detector and selection criteria values optimized for CCQE-like events, the concepts presented here are generic and can be adapted for various studies of exclusive v μ CCQE interactions in LArTPCs.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2015

SR2067 reveals a unique kinetic and structural signature for PPARγ partial agonism

Here, synthetic full agonists of PPARγ have been prescribed for the treatment of diabetes due to their ability to regulate glucose homeostasis and insulin sensitization. While the use of full agonists of PPARγ has been hampered due to severe side effects, partial agonists have shown promise due to their decreased incidence of such side effects in preclinical models. No kinetic information has been forthcoming in regard to the mechanism of full versus partial agonism of PPARγ to date. In this paper, we describe the discovery of a partial agonist, SR2067. A co-crystal structure obtained at 2.2 Å resolution demonstrates that interactions with the β-sheet are driven exclusively via hydrophobic interactions mediated through a naphthalene group, an observation that is unique from other partial agonists. Finally, surface plasmon resonance revealed that SR2067 binds to the receptor with higher affinity (K D = 513 nM) as compared to that of full agonist rosiglitazone, yet it has a much slower off rate compared to that of rosiglitazone.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗