Analysis of the CP structure of the Yukawa coupling between the Higgs boson and τ leptons in proton-proton collisions at s\sqrt{s} = 13 TeV

The first measurement of the CP structure of the Yukawa coupling between the Higgs boson and τ leptons is presented. The measurement is based on data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb$^{-1}$. The analysis uses the angular correlation between the decay planes of τ leptons produced in Higgs boson decays. The effective mixing angle between CP-even and CP-odd τ Yukawa couplings is found to be −1 ± 19°, compared to an expected value of 0 ± 21° at the 68.3% confidence level. The data disfavour the pure CP-odd scenario at 3.0 standard deviations. The results are compatible with predictions for the standard model Higgs boson

Degradation of polyamide reverse osmosis membranes in the presence of chloramine

Exposure to relatively low concentrations of chlorinated chemicals such as hypochlorite can reduce the performance and ultimately result in the failure of polyamide (PA) reverse osmosis membranes. Whereas the tolerance of PA membranes to chloramine solutions is considerably higher than that of hypochlorite, the presence of some metal ions can potentially catalyze and accelerate degradation reactions. Spectroscopic techniques are commonly used to qualitatively assess the chemical degradation of membranes by observing changes in structural peaks. This paper presents a technique to quantitatively evaluate changes in PA membranes exposed to chloramine by means of a peak ratio derived from a typical amide peak and an invariant peak in the same spectrum. The effect of some common metal ions and combinations of these on the peak ratio parameter derived from a typical amide peak is also reported

Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies

A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound 1zb is the most potent against both kinases with IC50 values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound 1zb was also tested against four melanoma cell lines and exerted superior potency (IC50 0.18-0.59 µM) compared to the reference standard drug, sorafenib (IC50 1.95-5.45 µM). Compound 1zb demonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC50 of 0.19 µM. Compound 1zb induces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds

Discovery of New Imidazo[2,1-b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure−activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC 50 values against cancer cells. Compound 27c with terminal open chain sulfonamide and 38a with a cyclic sulfamide moiety showed the highest activity in enzymatic and cellular assay, and both compounds were able to inhibit phosphorylation of MEK and ERK. Compound 38a was selected for testing its in vivo activity against melanoma. Cellular and animal activities are reported