The Ultra-Potent and Selective TLR8 Agonist VTX-294 Activates Human Newborn and Adult Leukocytes

Background: Newborns display distinct immune responses that contribute to susceptibility to infection and reduced vaccine responses. Toll-like receptor (TLR) agonists may serve as vaccine adjuvants, when given individually or in combination, but responses of neonatal leukocytes to many TLR agonists are diminished. TLR8 agonists are more effective than other TLR agonists in activating human neonatal leukocytes in vitro, but little is known about whether different TLR8 agonists may distinctly activate neonatal leukocytes. We characterized the in vitro immuno-stimulatory activities of a novel benzazepine TLR8 agonist, VTX-294, in comparison to imidazoquinolines that activate TLR8 (R-848; (TLR7/8) CL075; (TLR8/7)), with respect to activation of human newborn and adult leukocytes. Effects of VTX-294 and R-848 in combination with monophosphoryl lipid A (MPLA; TLR4) were also assessed. Methods: TLR agonist specificity was assessed using TLR-transfected HEK293 cells expressing a NF-κB reporter gene. TLR agonist-induced cytokine production was measured in human newborn cord and adult peripheral blood using ELISA and multiplex assays. Newborn and adult monocytes were differentiated into monocyte-derived dendritic cells (MoDCs) and TLR agonist-induced activation assessed by cytokine production (ELISA) and co-stimulatory molecule expression (flow cytometry). Results: VTX-294 was ∼100x more active on TLR8- than TLR7-transfected HEK cells (EC50, ∼50 nM vs. ∼5700 nM). VTX-294-induced TNF and IL-1β production were comparable in newborn cord and adult peripheral blood, while VTX-294 was ∼ 1 log more potent in inducing TNF and IL-1β production than MPLA, R848 or CL075. Combination of VTX-294 and MPLA induced greater blood TNF and IL-1β responses than combination of R-848 and MPLA. VTX-294 also potently induced expression of cytokines and co-stimulatory molecules HLA-DR and CD86 in human newborn MoDCs. Conclusions: VTX-294 is a novel ultra-potent TLR8 agonist that activates newborn and adult leukocytes and is a candidate vaccine adjuvant in both early life and adulthood

Low-energy cross section of the 7Be(p,g)8B solar fusion reaction from Coulomb dissociation of 8B

Final results from an exclusive measurement of the Coulomb breakup of 8B into 7Be+p at 254 A MeV are reported. Energy-differential Coulomb-breakup cross sections are analyzed using a potential model of 8B and first-order perturbation theory. The deduced astrophysical S_17 factors are in good agreement with the most recent direct 7Be(p,gamma)8B measurements and follow closely the energy dependence predicted by the cluster-model description of 8B by Descouvemont. We extract a zero-energy S_17 factor of 20.6 +- 0.8 (stat) +- 1.2 (syst) eV b.Comment: 14 pages including 16 figures, LaTeX, accepted for publication in Physical Review C. Minor changes in text and layou

The High-Acceptance Dielectron Spectrometer HADES

HADES is a versatile magnetic spectrometer aimed at studying dielectron production in pion, proton and heavy-ion induced collisions. Its main features include a ring imaging gas Cherenkov detector for electron-hadron discrimination, a tracking system consisting of a set of 6 superconducting coils producing a toroidal field and drift chambers and a multiplicity and electron trigger array for additional electron-hadron discrimination and event characterization. A two-stage trigger system enhances events containing electrons. The physics program is focused on the investigation of hadron properties in nuclei and in the hot and dense hadronic matter. The detector system is characterized by an 85% azimuthal coverage over a polar angle interval from 18 to 85 degree, a single electron efficiency of 50% and a vector meson mass resolution of 2.5%. Identification of pions, kaons and protons is achieved combining time-of-flight and energy loss measurements over a large momentum range. This paper describes the main features and the performance of the detector system

Core-coupled states and split proton-neutron quasi-particle multiplets in 122-126Ag

Neutron-rich silver isotopes were populated in the fragmentation of a 136Xe beam and the relativistic fission of 238U. The fragments were mass analyzed with the GSI Fragment separator and subsequently implanted into a passive stopper. Isomeric transitions were detected by 105 HPGe detectors. Eight isomeric states were observed in 122-126Ag nuclei. The level schemes of 122,123,125Ag were revised and extended with isomeric transitions being observed for the first time. The excited states in the odd-mass silver isotopes are interpreted as core-coupled states. The isomeric states in the even-mass silver isotopes are discussed in the framework of the proton-neutron split multiplets. The results of shell-model calculations, performed for the most neutron-rich silver nuclei are compared to the experimental data

Angular momentum population in fragmentation reactions

Neutron-deficient nuclei with N = 126 have been populated following projectile fragmentation of a 238U beam with energy 1 GeV/A. The decay of several previously reported isomers has been measured. This will allow us to calculate high-spin isomeric ratios and compare them with model calculations to allow a better understanding of the reaction mechanism.Algora, Alejandro, [email protected] ; Molina Palacios, Francisco Manuel, [email protected] ; Rubio Barroso, Berta, [email protected]

Coulomb dissociation of P 27 at 500 MeV/u

The proton-capture reaction Si26(p,γ)P27 was studied via Coulomb dissociation (CD) of P27 at an incident energy of about 500 MeV/u. The three lowest-lying resonances in P27 have been populated and their resonance strengths have been measured. In addition, a nonresonant direct-capture component was clearly identified and its astrophysical S factor measured. The experimental results are compared to Monte Carlo simulations of the CD process using a semiclassical model. Our thermonuclear reaction rates show good agreement with the rates from a recent compilation. With respect to the nuclear structure of P27 we have found evidence for a negative-parity intruder state at 2.88-MeV excitation energy

Search for lepton-number violating B+ -> X(-)l(+)l '(+) decays

We report on a search for eleven lepton-number violating processes B+ -> X(-)l(+)l'(+) with X- = K-, pi(-), rho(-), K*(-), or D- and l(+)/l'(+) = e(+) or mu(+), using a sample of 471 +/- 3 million B (B) over bar events collected with the BABAR detector at the PEP-II e(+)e(-) collider at the SLAC National Accelerator Laboratory. We find no evidence for any of these modes and place 90% confidence level upper limits on their branching fractions in the range (1.5-26) x 10(-7)

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)