pinecone/core-2020-05-10-deduplication huggingface dataset:
Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction

AbstractRecent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10
Measurements of six-body hadronic decays of the D0 charmed meson

AbstractUsing data collected by the FOCUS experiment at Fermilab, we report the discovery of the decay modes D0→K−π+π+π+π−π− and D0→π+π+π+π−π−π−. With a sample of 48±10 reconstructed D0→K−π+π+π+π−π− decays and 149±17 reconstructed D0→π+π+π+π−π−π− decays, we measure the following relative branching ratios: Γ(D0→K−π+π+π+π−π−)/Γ(D0→K−π+π+π−)=(2.70±0.58±0.38)×10−3,Γ(D0→π+π+π+π−π−π−)/Γ(D0→K−π+π+π−)=(5.23±0.59±1.35)×10−3,Γ(D0→π+π+π+π−π−π−)/Γ(D0→K−π+π+π+π−π−)=1.93±0.47±0.48. The first errors are statistical and the second are systematic. The branching fraction of the Cabibbo suppressed six-body decay mode is measured to be a factor of two higher than the branching fraction of the Cabibbo favored six-body decay mode
Mapping the Energy and Diffusion Landscapes of Membrane Proteins at the Cell Surface Using High-Density Single-Molecule Imaging and Bayesian Inference: Application to the Multiscale Dynamics of Glycine Receptors in the Neuronal Membrane

AbstractProtein mobility is conventionally analyzed in terms of an effective diffusion. Yet, this description often fails to properly distinguish and evaluate the physical parameters (such as the membrane friction) and the biochemical interactions governing the motion. Here, we present a method combining high-density single-molecule imaging and statistical inference to separately map the diffusion and energy landscapes of membrane proteins across the cell surface at ∼100 nm resolution (with acquisition of a few minutes). Upon applying these analytical tools to glycine neurotransmitter receptors at inhibitory synapses, we find that gephyrin scaffolds act as shallow energy traps (∼3 kBT) for glycine neurotransmitter receptors, with a depth modulated by the biochemical properties of the receptor-gephyrin interaction loop. In turn, the inferred maps can be used to simulate the dynamics of proteins in the membrane, from the level of individual receptors to that of the population, and thereby, to model the stochastic fluctuations of physiological parameters (such as the number of receptors at synapses). Overall, our approach provides a powerful and comprehensive framework with which to analyze biochemical interactions in living cells and to decipher the multiscale dynamics of biomolecules in complex cellular environments
Subleading corrections to the |Vub| determination from exclusive B decays

AbstractIt has been proposed to determine the CKM matrix element |Vub| in a model-independent way from a combination of rare and semileptonic B and D decays near the zero recoil point. An essential ingredient in such a determination is a heavy quark symmetry relation connecting the form-factors appearing in B→K∗e+e− to semileptonic form factors relevant for B→ρeν. We estimate the leading corrections to this symmetry relation, of order αs(mb) and Λ/mb, pointing out that they can be as large as 20%, depending on the value of the matrix element of a dimension-4 operator. Dimensional analysis estimates of this matrix element give a corresponding uncertainty in |Vub| of the order of a few percent
Non-equilibrium Behavior of the Magnetization in the Helimagnetic Phases of the Rare Earth Alloys R1–xYx (R = Gd, Tb, Dy)

AbstractWe have performed DC and AC magnetization measurements for the rare-earth magnetic alloy systems Gd0.62Y0.38, Tb0.86Y0.14, and Dy0.97Y0.03. These materials commonly exhibit a proper helical magnetic structure, and a ferromagnetic structure at lower temperatures. In all of these materials, a difference between zero-field-cooled (ZFC) magnetization and field-cooled (FC) magnetization and a hysteresis loop in the M-H curve have been observed in the helimagnetic phases. The non-equilibrium behavior is possibly caused by a common nature, e. g., chiral domain structures. In addition to the above behavior, strong non-linearity of the magnetization and slow spin dynamics have been observed around the Ńeel temperature only in Gd0.62Y0.38. The spin-glass like behavior observed in Gd0.62Y0.38 could be related to a novel glassy state such as a helical-glass state
Search for H→γγ produced in association with top quarks and constraints on the Yukawa coupling between the top quark and the Higgs boson using data taken at 7 TeV and 8 TeV with the ATLAS detector

AbstractA search is performed for Higgs bosons produced in association with top quarks using the diphoton decay mode of the Higgs boson. Selection requirements are optimized separately for leptonic and fully hadronic final states from the top quark decays. The dataset used corresponds to an integrated luminosity of 4.5 fb−1 of proton–proton collisions at a center-of-mass energy of 7 TeV and 20.3 fb−1 at 8 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess over the background prediction is observed and upper limits are set on the tt¯H production cross section. The observed exclusion upper limit at 95% confidence level is 6.7 times the predicted Standard Model cross section value. In addition, limits are set on the strength of the Yukawa coupling between the top quark and the Higgs boson, taking into account the dependence of the tt¯H and tH cross sections as well as the H→γγ branching fraction on the Yukawa coupling. Lower and upper limits at 95% confidence level are set at −1.3 and +8.0 times the Yukawa coupling strength in the Standard Model
Gauss–Bonnet black holes at the LHC: beyond the dimensionality of space

AbstractThe Gauss–Bonnet invariant is one of the most promising candidates for a quadratic curvature correction to the Einstein action in expansions of supersymmetric string theory. We study the evaporation of such Schwarzschild–Gauss–Bonnet black holes which could be formed at future colliders if the Planck scale is of order of TeV, as predicted by some modern brane world models. We show that, beyond the dimensionality of space, the corresponding coupling constant could be measured by the LHC. This opens new windows for physics investigation in spite of the possible screening of microphysics due to the event horizon
λ-backbone colorings along pairwise disjoint stars and matchings

AbstractGiven an integer λ≥2, a graph G=(V,E) and a spanning subgraph H of G (the backbone of G), a λ-backbone coloring of (G,H) is a proper vertex coloring V→{1,2,…} of G, in which the colors assigned to adjacent vertices in H differ by at least λ. We study the case where the backbone is either a collection of pairwise disjoint stars or a matching. We show that for a star backbone S of G the minimum number ℓ for which a λ-backbone coloring of (G,S) with colors in {1,…,ℓ} exists can roughly differ by a multiplicative factor of at most 2−1λ from the chromatic number χ(G). For the special case of matching backbones this factor is roughly 2−2λ+1. We also show that the computational complexity of the problem “Given a graph G with a star backbone S, and an integer ℓ, is there a λ-backbone coloring of (G,S) with colors in {1,…,ℓ}?” jumps from polynomially solvable to NP-complete between ℓ=λ+1 and ℓ=λ+2 (the case ℓ=λ+2 is even NP-complete for matchings). We finish the paper by discussing some open problems regarding planar graphs
Non-perturbative gluons in diffractive photo-production of J/Ψ

AbstractThe modifications induced in the calculation of the cross section of the diffractive process γγ→J/ΨJ/Ψ, when the gluon propagator is changed are analyzed. Instead of the usual perturbative gluon propagator, alternative forms obtained using non-perturbative methods like Dyson–Schwinger equations are used to consider in a more consistent way the contributions of the infrared region. The result shows a reduction in the differential cross-section for low momentum transfer once compared with the perturbative result, to be confirmed with future experimental results from TESLA
Endogenous rhythm of absence epilepsy: Relationship with general motor activity and sleep–wake states

SummaryThe rhythms of spontaneously occurring seizures (spike-wave discharges, SWD) and motor activity, as well as the relationship between SWD and sleep–wake states were investigated in the WAG/Rij rat model of absence epilepsy. In order to establish whether SWD are controlled by external (Zeitgebers) or by endogenous factors such as circadian influences or the state of vigilance, the study was performed in entrained and constant dim light conditions.EEG and motor activity were recorded in the 12:12 light–dark cycle and in constant dim light conditions. Circadian rhythmicity was found both for motor activity and the occurrence of SWD in conditions of entrainment. In constant dim light conditions also circadian rhythms emerged, however, the change in circadian parameters was opposite for the rhythm of SWD and motor activity. SWD were preceded mostly by passive wakefulness and by slow-wave sleep in both experimental conditions.It can be concluded that the rhythm of SWD seems to be generated and controlled by an endogenous mechanism distinct from that which controls the rhythm of motor activity. The relationship between SWD and sleep–wake states preceding their occurrences appeared to be unchanged, suggesting that the mechanism of generation of SWD is independent of the circadian timing system
Production of inclusive ϒ(1S) and ϒ(2S) in p–Pb collisions at sNN=5.02 TeV

AbstractWe report on the production of inclusive ϒ(1S) and ϒ(2S) in p–Pb collisions at sNN=5.02 TeV at the LHC. The measurement is performed with the ALICE detector at backward (−4.46<ycms<−2.96) and forward (2.03<ycms<3.53) rapidity down to zero transverse momentum. The production cross sections of the ϒ(1S) and ϒ(2S) are presented, as well as the nuclear modification factor and the ratio of the forward to backward yields of ϒ(1S). A suppression of the inclusive ϒ(1S) yield in p–Pb collisions with respect to the yield from pp collisions scaled by the number of binary nucleon–nucleon collisions is observed at forward rapidity but not at backward rapidity. The results are compared to theoretical model calculations including nuclear shadowing or partonic energy loss effects
Testing Grumillerʼs modified gravity at galactic scales

AbstractUsing galactic rotation curves, we test a – quantum motivated – gravity model that at large distances modifies the Newtonian potential when spherical symmetry is considered. In this model one adds a Rindler acceleration term to the rotation curves of disk galaxies. Here we consider a standard and a power-law generalization of the Rindler modified Newtonian potential that are hypothesized to play the role of dark matter in galaxies. The new, universal acceleration has to be – phenomenologically – determined. Our galactic model includes the mass of the integrated gas and stars for which we consider a free mass model. We test the model by fitting rotation curves of thirty galaxies that has been employed to test other alternative gravity models. We find that the Rindler parameters do not perform a suitable fit to the rotation curves in comparison to the Burkert dark matter profile, but the models achieve a similar fit as the NFWʼs profile does. However, the computed parameters of the Rindler gravity show some spread, posing the model to be unable to consistently explain the observed rotation curves
Precision measurements of A1n in the deep inelastic regime

AbstractWe have performed precision measurements of the double-spin virtual-photon asymmetry A1 on the neutron in the deep inelastic scattering regime, using an open-geometry, large-acceptance spectrometer and a longitudinally and transversely polarized 3He target. Our data cover a wide kinematic range 0.277≤x≤0.548 at an average Q2 value of 3.078 (GeV/c)2, doubling the available high-precision neutron data in this x range. We have combined our results with world data on proton targets to make a leading-order extraction of the ratio of polarized-to-unpolarized parton distribution functions for up quarks and for down quarks in the same kinematic range. Our data are consistent with a previous observation of an A1n zero crossing near x=0.5. We find no evidence of a transition to a positive slope in (Δd+Δd¯)/(d+d¯) up to x=0.548
Navier–Stokes flow in converging–diverging distensible tubes

AbstractWe use a method based on the lubrication approximation in conjunction with a residual-based mass-continuity iterative solution scheme to compute the flow rate and pressure field in distensible converging–diverging tubes for Navier–Stokes fluids. We employ an analytical formula derived from a one-dimensional version of the Navier–Stokes equations to describe the underlying flow model that provides the residual function. This formula correlates the flow rate to the boundary pressures in straight cylindrical elastic tubes with constant-radius. We validate our findings by the convergence toward a final solution with fine discretization as well as by comparison to the Poiseuille-type flow in its convergence toward analytic solutions found earlier in rigid converging–diverging tubes. We also tested the method on limiting special cases of cylindrical elastic tubes with constant-radius where the numerical solutions converged to the expected analytical solutions. The distensible model has also been endorsed by its convergence toward the rigid Poiseuille-type model with increasing the tube wall stiffness. Lubrication-based one-dimensional finite element method was also used for verification. In this investigation five converging–diverging geometries are used for demonstration, validation and as prototypes for modeling converging–diverging geometries in general
ICD risk stratification studies – EU-CERT-ICD and the European perspective

AbstractBackground and rationaleIn patients with ischemic or non-ischemic cardiomyopathy and impaired left ventricular ejection fraction, treatment with implantable cardioverter-defibrillator (ICD) has been shown to improve survival and guidelines recommend their use for primary prevention of sudden cardiac death. Experts disagree regarding the validity of decade-old trial results as the basis for this recommendation, therefore, reconsideration of prophylactic ICD treatment is needed.EU-CERT-ICD, DANISH-ICD and DO-ITIn order to update the evidence on prophylactic ICD treatment, several prospective studies are underway in Europe. The prospective EU-CERT-ICD cohort study (NCT 02064192) is enrolling 2500 patients and compares patients undergoing first ICD implantation with controls with an earlier clinical decision to go without ICD implantation strictly unrelated to the study. The DANISH ICD study (NCT 00542945) has randomized 1000 patients with dilated cardiomyopathy and an LVEF ≤35% (1:1 ICD implantation vs. control). The prospective DO-IT multicenter registry will include 1500 ICD patients in multiple Dutch high-volume implanting centers. Due to the widespread use of ICD therapy, new randomized trials seem not straightforward to envisage in many countries.ConclusionThe above described ICD studies will provide additional evidence regarding the effectiveness of primary prophylactic ICDs in Europe and may have an impact on ICD treatment guidelines. They could also help to design randomized trials in low risk patients
Diffusion as a singular homogenization of the Frenkel–Kontorova model

AbstractIn this work, we consider a general fully overdamped Frenkel–Kontorova model. This model describes the dynamics of an infinite chain of particles, moving in a periodic landscape. Our aim is to describe the macroscopic behavior of this system. We study a singular limit corresponding to a high density of particles moving in a vanishing periodic landscape. We identify the limit equation which is a nonlinear diffusion equation. Our homogenization approach is done in the framework of viscosity solutions
How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial

AbstractBackgroundIn a phase III trial of patients with unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC) with a poor prognosis, palliative concurrent chemoradiotherapy (CRT) provided a significantly better outcome than chemotherapy alone, except among performance status (PS) 2 patients. In the present subgroup analysis, we evaluated the effect on patients aged ≥ 70 years (42% of all included) compared with patients aged < 70 years enrolled in the trial.Patients and MethodsAll patients received 4 courses of intravenous carboplatin and oral vinorelbine. The experimental arm also received radiotherapy (42 Gy in 15 fractions). The included patients were required to have large tumors (> 8 cm), weight loss (> 10% within the previous 6 months) and/or PS 2.ResultsThe overall survival was increased among the CRT patients in both age groups, but the difference was significant only in patients aged < 70 years (median survival, 14.8 vs. 9.7 months; P = .001; age ≥ 70 years, median survival, 10.2 vs. 9.1 months; P = .09). Patients aged ≥ 70 years experienced better preserved health-related quality of life (QOL) and significantly less hematologic toxicity. The 2- and 3-year survival was significantly increased in both age groups receiving CRT.ConclusionElderly patients aged ≥ 70 years with unresectable, stage III, locally advanced, NSLCL and a poor prognosis can tolerate CRT with the doses adjusted to age and palliative intent. These results indicate that CRT can provide both survival and QOL benefits in elderly patients, except for those with PS 2 or worse. The male predominance in the ≥ 70-year-age group and the reduced chemotherapy intensity for the patients aged > 75 years might explain the lack of significant survival improvement among those patients aged ≥ 70 years
Jet-like correlations with direct-photon and neutral-pion triggers at sNN=200 GeV

AbstractAzimuthal correlations of charged hadrons with direct-photon (γdir) and neutral-pion (π0) trigger particles are analyzed in central Au+Au and minimum-bias p+p collisions at sNN=200 GeV in the STAR experiment. The charged-hadron per-trigger yields at mid-rapidity from central Au+Au collisions are compared with p+p collisions to quantify the suppression in Au+Au collisions. The suppression of the away-side associated-particle yields per γdir trigger is independent of the transverse momentum of the trigger particle (pTtrig), whereas the suppression is smaller at low transverse momentum of the associated charged hadrons (pTassoc). Within uncertainty, similar levels of suppression are observed for γdir and π0 triggers as a function of zT (≡pTassoc/pTtrig). The results are compared with energy-loss-inspired theoretical model predictions. Our studies support previous conclusions that the lost energy reappears predominantly at low transverse momentum, regardless of the trigger energy
Fugitive emissions of methane from abandoned, decommissioned oil and gas wells

AbstractThis study considered the fugitive emissions of methane (CH4) from former oil and gas exploration and production wells drilled to exploit conventional hydrocarbon reservoirs onshore in the UK. This study selected from the 66% of all onshore wells in the UK which appeared to be properly decommissioned (abandoned) that came from 4 different basins and were between 8 and 79years old. The soil gas above each well was analysed and assessed relative to a nearby control site of similar land use and soil type. The results showed that of the 102 wells considered 30% had soil gas CH4 at the soil surface that was significantly greater than their respective control. Conversely, 39% of well sites had significant lower surface soil gas CH4 concentrations than their respective control. We interpret elevated soil gas CH4 concentrations to be the result of well integrity failure, but do not know the source of the gas nor the route to the surface. Where elevated CH4 was detected it appears to have occurred within a decade of it being drilled. The flux of CH4 from wells was 364±677kg CO2eq/well/year with a 27% chance that the well would have a negative flux to the atmosphere independent of well age. This flux is low relative to the activity commonly used on decommissioned well sites (e.g. sheep grazing), however, fluxes from wells that have not been appropriately decommissioned would be expected to be higher
A robust jet reconstruction algorithm for high-energy lepton colliders

AbstractWe propose a new sequential jet reconstruction algorithm for future lepton colliders at the energy frontier. The Valencia algorithm combines the natural distance criterion for lepton colliders with the greater robustness against backgrounds of algorithms adapted to hadron colliders. Results on a detailed Monte Carlo simulation of tt¯ and ZZ production at future linear e+e− colliders (ILC and CLIC) with a realistic level of background overlaid, show that it achieves better performance in the presence of background than the classical algorithms used at previous e+e− colliders
Fulling–Davies–Unruh effect and spontaneous excitation of an accelerated atom interacting with a quantum scalar field

AbstractWe investigate, from the point of view of a coaccelerated frame, the spontaneous excitation of a uniformly accelerated two-level atom interacting with a scalar field in a thermal state at a finite temperature T and show that the same spontaneous excitation rate for the uniformly accelerated atom in the Minkowski vacuum obtained in the inertial frame can only be recovered in the coaccelerated frame assuming a thermal bath at the Fulling–Davies–Unruh temperature TFDU=a/2π for what appears to be the Minkowski vacuum to the inertial observer. Our discussion provides another example of a physical process different from those examined before in the literature to better understand the Fulling–Davies–Unruh effect