Adjusting the Fitting of Fluorescence-Based Dose-Response Kinase Inhibition Assay to Account for Fluorescent Inhibitors

Fluorescence is routinely used to monitor kinase inhibition in commercial assays. Occasionally fluorescent compounds can interfere with the fluorescent reading. To address this issue, the problematic data are usually truncated to improve the fit, however, this approach raises ethical and reproducibility concerns. Instead, it is suggested to adjust the fitting formula, to account for the autofluorescence of the compounds and improve the fit of the data compared with a naive approach. Finally, it was noticed that truncating the data can result in a small underestimation of the IC50 values and should therefore be used carefully

Independence of spin-orbit torques from the exchange bias direction in Ni81_{81}Fe19_{19}/IrMn bilayers

We investigated a possible correlation between spin Hall angles and exchange bias in Ni$_{81}$Fe$_{19}$/IrMn samples by performing spin torque ferromagnetic resonance measurements. This correlation is probed by patterning of Ni$_{81}$Fe$_{19}$/IrMn bilayers in different relative orientations with respect to the exchange bias direction. The measured voltage spectra allow a quantitative determination of spin Hall angles, which are independent of the orientation around 2.8\pm0.3%.Comment: 10 page

A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells

Cavernous vascular malformations occur with a frequency of 1:200 and can cause recurrent headaches, seizures and hemorrhagic stroke if located in the brain. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein expression depending on the inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein but not for the two others. In addition to proving loss of function at the protein level, our data are the first to demonstrate endothelial cell mosaicism within cavernous tissues and provide clear pathogenetic evidence that the endothelial cell is the cell of disease origin