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At least 487 records · Page 27

Activation of human STING by a molecular glue-like compound

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.

60 APPLIED LIFE SCIENCES↗

Explaining machine-learning models for gamma-ray detection and identification

As more complex predictive models are used for gamma-ray spectral analysis, methods are needed to probe and understand their predictions and behavior. Recent work has begun to bring the latest techniques from the field of Explainable Artificial Intelligence (XAI) into the applications of gamma-ray spectroscopy, including the introduction of gradient-based methods like saliency mapping and Gradient-weighted Class Activation Mapping (Grad-CAM), and black box methods like Local Interpretable Model-agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP). In addition, new sources of synthetic radiological data are becoming available, and these new data sets present opportunities to train models using more data than ever before. In this work, we use a neural network model trained on synthetic NaI(Tl) urban search data to compare some of these explanation methods and identify modifications that need to be applied to adapt the methods to gamma-ray spectral data. We find that the black box methods LIME and SHAP are especially accurate in their results, and recommend SHAP since it requires little hyperparameter tuning. We also propose and demonstrate a technique for generating counterfactual explanations using orthogonal projections of LIME and SHAP explanations.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

GW190814: Gravitational Waves from the Coalescence of a 23 Solar Mass Black Hole with a 2.6 Solar Mass Compact Object

We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67Me (all measurements quoted at the 90% credible level). The gravitational-wavesignal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to18.5 deg2 at a distance of-+2414541Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves,-+0.1120.0090.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to 0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries.

Gravitational wave astronomy↗

Resonant instabilities mediated by drag and electrostatic interactions in laboratory and astrophysical dusty plasmas

Dusty plasmas are known to support a diverse range of instabilities, including both generalizations of standard plasma instabilities and ones caused by effects specific to dusty systems. It has been recently demonstrated that a novel broad class of streaming instabilities, termed resonant drag instabilities (RDIs), can be attributed to a particular resonance phenomenon, manifested by defective eigenvalues of the linearized dust/fluid system. In this work, it is demonstrated that this resonance phenomenon is not unique to RDIs and can be used as a framework to understand a wider range of instabilities, termed resonant instabilities. Particular attention is given to the filamentary ionization instability seen in laboratory dusty plasmas and to the two-stream instability. It is shown that, due to the commonalities in underlying physics between the dust-ion-acoustic two-stream instability and the acoustic RDI, these instabilities should be relevant in strongly overlapping regimes in astrophysical dusty plasmas. Further, it is proposed that a similar overlap in the experimental accessibility of these modes (and of the filamentary instability) allows for the possibility of experimental investigation in the laboratory of complex and astrophysically relevant instability dynamics.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Monolayer CrCl 3 as an Ideal Test Bed for the Universality Classes of 2D Magnetism

The monolayer halides CrX 3 (X=Cl, Br, I) attract significant attention for realizing 2D magnets with genuine long-range order (LRO), challenging the Mermin-Wagner theorem. In this work, we show that monolayer CrCl 3 has the unique benefit of exhibiting tunable magnetic anisotropy upon applying a compressive strain. This opens the possibility to use CrCl 3 for producing and studying both ferromagnetic and antiferromagnetic 2D Ising-type LRO as well as the Berezinskii-Kosterlitz-Thouless (BKT) regime of 2D magnetism with quasi-LRO. Using state-of-the-art density functional theory, we explain how realistic compressive strain could be used to tune the monolayer's magnetic properties so that it could exhibit any of these phases. Building on large-scale quantum Monte Carlo simulations, we compute the phase diagram of strained CrCl 3 , as well as the magnon spectrum with spin-wave theory. Our results highlight the eminent suitability of monolayer CrCl 3 to achieve very high BKT transition temperatures, around 50 K, due to their singular dependence on the weak easy-plane anisotropy of the material.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Creation of skyrmions in van der Waals ferromagnet Fe 3 GeTe 2 on (Co/Pd) n superlattice

Magnetic skyrmions are topological spin textures, which usually exist in noncentrosymmetric materials where the crystal inversion symmetry breaking generates the so-called Dzyaloshinskii-Moriya interaction. This requirement unfortunately excludes many important magnetic material classes, including the recently found two-dimensional van der Waals (vdW) magnetic materials, which offer unprecedented opportunities for spintronic technology. Using photoemission electron microscopy and Lorentz transmission electron microscopy, we investigated and stabilized Néel-type magnetic skyrmion in vdW ferromagnetic Fe 3 GeTe 2 on top of (Co/Pd) n in which the Fe 3 GeTe 2 has a centrosymmetric crystal structure. We demonstrate that the magnetic coupling between the Fe 3 GeTe 2 and the (Co/Pd) n could create skyrmions in Fe 3 GeTe 2 without the need of an external magnetic field. Our results open exciting opportunities in spintronic research and the engineering of topologically protected nanoscale features by expanding the group of skyrmion host materials to include these previously unknown vdW magnets.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

NASA Discipline Neuroscience↗

Validating sequential Monte Carlo for gravitational-wave inference

Nested sampling (NS) is the preferred stochastic sampling algorithm for gravitational-wave inference for compact binary coalescences. It can handle the complex nature of the gravitational-wave likelihood surface and provides an estimate of the Bayesian model evidence. However, there is another class of algorithms that meets the same requirements, but has not been used for gravitational-wave analyses: sequential Monte Carlo (SMC), an extension of importance sampling that maps samples from an initial density to a target density via a series of intermediate densities. In this work, we validate a type of SMC algorithm, called persistent sampling (PS), for gravitational-wave inference. We consider a range of different scenarios including binary black holes and binary neutron stars and real and simulated data and show that PS produces results that are consistent with NS whilst being, on average, 2 times more efficient and 2.74 times faster. This demonstrates that PS is a viable alternative to NS that should be considered for future gravitational-wave analyses.

black hole mergers↗

Higher-order flux difference splitting schemes for the Euler equations using upstream interpolations

A class of explicit two time-level, 2p + 1 space-point, (2p 1)-th order, upwind-biased flux difference splitting schemes are proposed for the numerical advection based on Lagrange's interpolation, and the method is an accord with the physical domain of dependence. A normalized Jacobian coefficient matrix is introduced to convert the schemes to hyperbolic systems of conservation laws, and approaches to make the higher-order schemes total variation stable are discussed. Accuracy and stability of the present schemes are examined, and implicit total variation diminishing schemes are developed for steady-state calculations.Application to gasdynamic problems for both steady and unsteady flows covering a wide range of Mach numbers is considered, and results for a blast wave passing a cylinder, and head-on collision of two blast waves over a circular arc, are presented. The flow patterns were found to be symmetric, and good resolution of flow structures was obtained.

Yang, J. Y.↗

Evaluation of Low Dose Silicon Carbide Temperature Monitors

Thermocouples are generally used to provide real-time temperature indications in instrumented tests performed at materials and test reactors. Melt wires or paint spots are often included in such tests as an independent technique of detecting peak temperatures incurred during irradiation. In addition, less expensive static capsule tests, which have no leads attached for real-time data transmission, often rely on melt wires and paint spots as a post-irradiation technique for peak temperature indication. Unfortunately, these techniques are limited in that they can only detect whether a single temperature is or is not exceeded. Silicon carbide (SiC) monitors are advantageous because a single monitor can be used to determine the peak temperature reached within a relatively broad range (200 – 800°C). Although the use of SiC monitors was proposed more than five decades ago, the ultimate performance limits of this technique are not fully understood. The Nuclear Science User Facilities (NSUF) is the United States Department of Energy Office of Nuclear Energy's only designated nuclear energy user facility. Its mission is to provide nuclear energy researchers access to world-class capabilities and to facilitate the advancement of nuclear science and technology. This mission is supported by providing access to state-of-the-art experimental irradiation testing, post irradiation examination facilities, and high performance computing capabilities as well as technical and scientific assistance for the design and execution of projects. As part of an NSUF project, low dose silicon carbide monitors were irradiated in the Belgian Reactor 2 and were then evaluated both at the SCK•CEN and at Idaho National Laboratory's High Temperature Test Laboratory to determine their peak temperature achieved during irradiation. The technical significance of this work was that the monitors were irradiated to a dose that was significantly less than recommended in published literature. This paper will discuss the evaluation process, the irradiation test, and the performance of the low dose silicon carbide temperature monitors.

36 MATERIALS SCIENCE↗

Measurements of long-range two-particle correlation over a wide pseudorapidity range in p–Pb collisions at $ \sqrt{s_{\textrm{NN}}}$ = 5.02 TeV

Correlations in azimuthal angle extending over a long range in pseudorapidity between particles, usually called the “ridge” phenomenon, were discovered in heavy-ion collisions, and later found in pp and p–Pb collisions. In large systems, they are thought to arise from the expansion (collective flow) of the produced particles. Extending these measurements over a wider range in pseudorapidity and final-state particle multiplicity is important to understand better the origin of these long-range correlations in small collision systems. In this Letter, measurements of the long-range correlations in p–Pb collisions at $\sqrt{^SNN}$ = 5.02 TeV are extended to a pseudorapidity gap of Δη ~ 8 between particles using the ALICE forward multiplicity detectors. After suppressing non-flow correlations, e.g., from jet and resonance decays, the ridge structure is observed to persist up to a very large gap of Δη ~ 8 for the first time in p–Pb collisions. This shows that the collective flow-like correlations extend over an extensive pseudorapidity range also in small collision systems such as p–Pb collisions. The pseudorapidity dependence of the second-order anisotropic flow coefficient, v 2 (η), is extracted from the long-range correlations. The v 2 (η) results are presented for a wide pseudorapidity range of –3.1 < η < 4.8 in various centrality classes in p–Pb collisions. To gain a comprehensive understanding of the source of anisotropic flow in small collision systems, the v 2 (η) measurements are compared with hydrodynamic and transport model calculations. The comparison suggests that the final-state interactions play a dominant role in developing the anisotropic flow in small collision systems.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Systematic study of nuclear effects in p + Al , p + Au , d + Au , and He 3 + Au collisions at s N N = 200 GeV using π 0 production

The PHENIX Collaboration presents a systematic study of inclusive π 0 production from p + p , p + Al , p + Au , d + Au , and He 3 + Au collisions at s N N = 200 GeV . Measurements were performed with different centrality selections as well as the total inelastic, 0–100%, selection for all collision systems. For 0–100% collisions, the nuclear-modification factors, R x A , are consistent with unity for p T above 8 GeV / c , but exhibit an enhancement in peripheral collisions and a suppression in central collisions. The enhancement and suppression characteristics are similar for all systems for the same centrality class. It is shown that for high- p T - π 0 production, the nucleons in the d and He 3 interact mostly independently with the Au nucleus and that the counterintuitive centrality dependence is likely due to a physical correlation between multiplicity and the presence of a hard scattering process. These observations disfavor models where parton energy loss has a significant contribution to nuclear modifications in small systems. Nuclear modifications at lower p T resemble the Cronin effect—an increase followed by a peak in central or inelastic collisions and a plateau in peripheral collisions. The peak height has a characteristic ordering by system size as p + Au > d + Au > He 3 + Au > p + Al . For collisions with Au ions, current calculations based on initial-state cold nuclear matter effects result in the opposite order, suggesting the presence of other contributions to nuclear modifications, in particular at lower p T .

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

New Stagnation Arc Jet Model Design for Testing ADEPT 3-D Carbon Cloth

The ADEPT concept has been considered as an entry, descent and landing system to enable Human Mars class missions. Ground rules for the Mars studies required aerocapture, orbit, and then entry. The design utilizes a 3-D woven carbon cloth fabric as both heatshield and primary structure and design guidelines required 6 layers remaining after all entry events. The peak heating predicted for the ADEPT carbon cloth was 35 Wcm2 and resulting temperatures were predicted to be 1400K. Predictions for carbon mass loss were performed using equilibrium thermochemistry, which is only accurate for T2000K. Carbon oxidation is kinetically controlled at T2000K, and mass loss drops off considerably from equilibrium values. Design of the cloth thickness and mass would be significantly reduced if kinetics were considered. This effort was to design a stagnation test article design that could be used in the AHF with varying levels of oxygen where the results could be used to develop an engineering model to describe the recession rate of the carbon as a function of the partial pressure of monotomic oxygen.

carbon cloth↗

Chandra Deep X-ray Observation of a Typical Galactic Plane Region and Near-Infrared Identification

Using the Chandra Advanced CCD Imaging Spectrometer Imaging array (ACIS-I), we have carried out a deep hard X-ray observation of the Galactic plane region at (l,b) approx. (28.5 deg,0.0 deg), where no discrete X-ray source has been reported previously. We have detected 274 new point X-ray sources (4 sigma confidence) as well as strong Galactic diffuse emission within two partidly overlapping ACIS-I fields (approx. 250 sq arcmin in total). The point source sensitivity was approx. 3 x 10(exp -15)ergs/s/sq cm in the hard X-ray band (2-10 keV and approx. 2 x 10(exp -16) ergs/s/sq cm in the soft band (0.5-2 keV). Sum of all the detected point source fluxes account for only approx. 10 % of the total X-ray fluxes in the field of view. In order to explain the total X-ray fluxes by a superposition of fainter point sources, an extremely rapid increase of the source population is required below our sensitivity limit, which is hardly reconciled with any source distribution in the Galactic plane. Therefore, we conclude that X-ray emission from the Galactic plane has truly diffuse origin. Only 26 point sources were detected both in the soft and hard bands, indicating that there are two distinct classes of the X-ray sources distinguished by the spectral hardness ratio. Surface number density of the hard sources is only slightly higher than observed at the high Galactic latitude regions, strongly suggesting that majority of the hard X-ray sources are active galaxies seen through the Galactic plane. Following the Chandra observation, we have performed a near-infrared (NIR) survey with SOFI at ESO/NTT to identify these new X-ray sources. Since the Galactic plane is opaque in NIR, we did not see the background extragalactic sources in NIR. In fact, only 22 % of the hard sources had NIR counterparts which are most likely to be Galactic origin. Composite X-ray energy spectrum of those hard X-ray sources having NIR counterparts exhibits a narrow approx. 6.7 keV iron emission line, which is a signature of Galactic quiescent cataclysmic variables (CVs).

Ebisawa, K.↗

Search for dark matter produced in association with a single top quark and an energetic W boson in $\sqrt{s}=$ 13 TeV $pp$ collisions with the ATLAS detector

This paper presents a search for dark matter, $χ$, using events with a single top quark and an energetic W boson. The analysis is based on proton–proton collision data collected with the ATLAS experiment at $\sqrt{s}=$ 13 TeV during LHC Run 2 (2015–2018), corresponding to an integrated luminosity of 139 fb -1 . The search considers final states with zero or one charged lepton (electron or muon), at least one $b$-jet and large missing transverse momentum. In addition, a result from a previous search considering two-charged-lepton final states is included in the interpretation of the results. The data are found to be in good agreement with the Standard Model predictions and the results are interpreted in terms of 95% confidence-level exclusion limits in the context of a class of dark matter models involving an extended two Higgs-doublet sector together with a pseudoscalar mediator particle. The search is particularly sensitive to on-shell pro duction of the charged Higgs boson state, $H$ ± , arising from the two-Higgs-doublet mixing, and its semi-invisible decays via the mediator particle, $a$: $H$ ± → $W$ ± $a$(→ $χ$ $χ$). Signal models with $H$ ± masses up to 1.5 TeV and a masses up to 350 GeV are excluded assuming a tan $β$ value of 1. For masses of a of 150 (250) GeV, tan $β$ values up to 2 are excluded for $H$ ± masses between 200 (400) GeV and 1.5 TeV. Signals with tan $β$ values between 20 and 30 are excluded for $H$ ± masses between 500 and 800 GeV.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, including base pairs and base mis-pairs, that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase (aaRS) interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. We also identified Leishmania major threonyl-tRNA synthetase (ThrRS) inhibitors from the same library. We discuss why chemotherapies targeting multiple aaRSs should be less prone to the evolution of resistance than monotherapeutic or synergistic combination chemotherapies targeting only one aaRS.

59 BASIC BIOLOGICAL SCIENCES↗

BASS. XXXIII. Swift-BAT Blazars and Their Jets through Cosmic Time

We derive the most up-to-date Swift-Burst Alert Telescope (BAT) blazar luminosity function in the 14–195 keV range, making use of a clean sample of 118 blazars detected in the BAT 105 month survey catalog, with newly obtained redshifts from the BAT Active Galatic Nucleus Spectroscopic Survey. We determine the best-fit X-ray luminosity function for the whole blazar population, as well as for flat-spectrum radio quasars (FSRQs) alone. The main results are: (1) at any redshift, BAT detects the most luminous blazars, above any possible break in their luminosity distribution, which means we cannot differentiate between density and luminosity evolution; (2) the whole blazar population, dominated by FSRQs, evolves positively up to redshift z ~ 4.3, confirming earlier results and implying lower number densities of blazars at higher redshifts than previously estimated. The contribution of this source class to the cosmic X-ray background at 14–195 keV can range from 5%–18%, while possibly accounting for 100% of the MeV background. We also derived the average 14 keV–10 GeV spectral energy distribution for BAT blazars, which allows us to predict the number counts of sources in the MeV range, as well as the expected number of high-energy (>100 TeV) neutrinos. A mission like COSI will detect 40 MeV blazars, of which two may have coincident neutrino detections. Finally, taking into account beaming selection effects, the distribution and properties of the parent population of these extragalactic jets are derived. We find that the distribution of viewing angles is quite narrow, with most sources aligned within <5° of the line of sight. Moreover, the average Lorentz factor, $\langle$Γ$\rangle$ = 8–12, is lower than previously suggested for these powerful sources.

79 ASTRONOMY AND ASTROPHYSICS↗