Nanoparticular Inhibitors of Flavivirus Proteases from Zika, West Nile and Dengue Virus Are Cell-Permeable Antivirals

Viral proteases have been established as drug targets in several viral diseases including human immunodeficiency virus and hepatitis C virus infections due to the essential role of these enzymes in virus replication. In contrast, no antiviral therapy is available to date against flaviviral infections including those by Zika virus (ZIKV), West Nile virus (WNV), or dengue virus (DENV). Numerous potent inhibitors of flaviviral proteases have been reported; however, a huge gap remains between the in vitro and intracellular activities, possibly due to low cellular uptake of the charged compounds. Here, we present an alternative, nanoparticular approach to antivirals. Conjugation of peptidomimetic inhibitors and cell-penetrating peptides to dextran yielded chemically defined nanoparticles that were potent inhibitors of flaviviral proteases. Peptide-dextran conjugates inhibited viral replication and infection in cells at nontoxic, low micromolar or even nanomolar concentrations. Thus, nanoparticular antivirals might be alternative starting points for the development of broad-spectrum antiflaviviral drugs.C.N. thanks the Australian Research Council for a Discovery Early Career Research Award (DE190100015) and the Freie Universität Berlin for a Rising Star fellowship

Stopping power and collective flow of nuclear matter in the reaction Ar+Pb at 0.8 GeV/u

Charged-particle exclusive data for Ar+Pb collisions at 0.772 GeV/u are analyzed in terms of collective variables for the event shapes in momentum space. Semicentral collisions lead to sidewards flow whereas nearly head-on collisions have spherical shapes in the c.m. frame, resulting from complete stopping of projectile motion. The hydrodynamical model predictions agree qualitatively with the data whereas the standard cascade model disagrees, lacking in stopping power and collective flow

Collective motion in nucleus-nucleus collisions at 800 MeV/nucleon

Semicentral Ar+KCl, La+La, and Ar+Pb collisions at 800 MeV/nucleon were studied using a streamer chamber. The results are analyzed in the framework of the transverse momentum analysis and in terms of the average sphericity matrix. A critical examination of the analysis procedures, both experimental and theoretical, is given. New procedures are described to account for overall momentum conservation in the reaction, and to correct for azimuthal variations in the detection efficiency. Average transverse momenta per nucleon in the reaction plane are presented for deuterons emitted in the forward hemisphere, as these provide the most reliable information. A Vlasov-Uehling-Uhlenbeck calculation with a stiff equation of state gives a good fit to the momenta in the Ar+Pb reaction. Flow effects parametrized further using the sphericity tensor are found stronger than in the cascade model and consistently weaker than predicted by hydrodynamics. Parameters from the sphericity tensor exhibit a larger variation as a function of multiplicity than do the average momenta per nucleon

Compression effects in relativistic nucleus-nucleus collisions

The negative-pion multiplicity is measured for central collisions of 40Ar with KCl at eight energies from 0.36 to 1.8 GeV/nucleon and for 4He on KCl and 40Ar on BaI2 at 977 and 772 MeV/nucleon, respectively. A systematic discrepancy with a cascade-model calculation which fits proton- and pion-nucleus cross sections but omits potential-energy effects is used to derive the energy going into bulk compression of the system. A value of the incompressibility constant of K=240 MeV is extracted in a parabolic form of the nuclear-matter equation of state

Collective motion in Ar+Pb collision at beam energies between 400 and 1800 MeV/nucleon

The energy dependence of rapidity distributions and flow effects was studied in central Ar+Pb collisions at 400, 800, and 1800 MeV/nucleon using a streamer chamber. Rapidity distributions for proton and pions are found to have a Gaussian shape whereas those for deuterons exhibit a two-peak structure at the two higher energies. The average in-plane transverse momentum per/nucleon and per/event shows saturation of flow around 800 MeV/nucleon for this asymmetric system. The aspect ratio of the sphericity tensor is closely correlated with the flow angle. This correlation appears to be independent of beam energy. The number of participating nucleons in central collisions varies from 213 at 400 to 135 at 1800 MeV/nucleon indicating that at the lowest energy almost the entire target nucleus participates in the collision.weitere Autoren

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.