AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Combined measurements of Higgs boson couplings in proton- proton collisions at v s=13TeV

Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton-proton collision data set recorded with the CMS detector in 2016 at fb-1. The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a W or Z boson, or a top quark-antiquark pair) and the following decay modes: H, ZZ, WW, , bb, and . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be =1.17 +/- 0.10, assuming a Higgs boson mass of 125.09. Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.Peer reviewe

Measurement of prompt D-0 and D-0 meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root S-NN=5.02 TeV

SCOAP

Electroweak measurements in electron–positron collisions at w-boson-pair energies at lep

Contains fulltext : 121524.pdf (preprint version ) (Open Access

What is the Expected Return on a Stock?

We derive a formula that expresses the expected return on a stock in terms of the risk-neutral variance of the market and the stock's excess risk-neutral variance relative to the average stock. These components can be computed from index and stock option prices; the formula has no free parameters. We test the theory in-sample by running panel regressions of stock returns onto risk-neutral variances. The formula performs well at 6-month and 1-year forecasting horizons, and our predictors drive out beta, size, book-to-market, and momentum. Out-of-sample, we find that the formula outperforms a range of competitors in forecasting individual stock returns. Our results suggest that there is considerably more variation in expected returns, both over time and across stocks, than has previously been acknowledged

Search for Charged Higgs bosons: Combined Results Using LEP Data

The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for pair-produced charged Higgs bosons in the framework of Two Higgs Doublet Models (2HDMs). The data of the four experiments are statistically combined. The results are interpreted within the 2HDM for Type I and Type II benchmark scenarios. No statistically significant excess has been observed when compared to the Standard Model background prediction, and the combined LEP data exclude large regions of the model parameter space. Charged Higgs bosons with mass below 80 GeV/c^2 (Type II scenario) or 72.5 GeV/c^2 (Type I scenario, for pseudo-scalar masses above 12 GeV/c^2) are excluded at the 95% confidence level