Response to comment on "Reexamination of 2.5-Ga 'whiff' of oxygen interval points to anoxic ocean before GOE".

Sedimentological, textural, and microscale analyses of the Mount McRae Shale revealed a complex postdepositional history, previously unrecognized in bulk geochemical studies. We found that metal enrichments in the shale do not reside with depositional organic carbon, as previously proposed by Anbar ., but with late-stage pyrite, compromising claims for a "whiff" of oxygen ~50 million years before the Great Oxygenation Event.

Reexamination of 2.5-Ga "whiff" of oxygen interval points to anoxic ocean before GOE.

Transient appearances of oxygen have been inferred before the Great Oxygenation Event (GOE) [∼2.3 billion years (Ga) ago] based on redox-sensitive elements such as Mo and S—most prominently from the ∼2.5-Ga Mount McRae Shale in Western Australia.

Tomographic mapping of the hidden dimension in quasi-particle interference.

Quasiparticle interference (QPI) imaging is well established to study the low-energy electronic structure in strongly correlated electron materials with unrivalled energy resolution. Yet, being a surface-sensitive technique, the interpretation of QPI only works well for anisotropic materials, where the dispersion in the direction perpendicular to the surface can be neglected and the quasiparticle interference is dominated by a quasi-2D electronic structure. Here, we explore QPI imaging of galena, a material with an electronic structure that does not exhibit pronounced anisotropy.

In Silico and in Vitro Assessment of OATP1B1 Inhibition in Drug Discovery.

The organic anion-transporting polypeptide 1B1 transporter belongs to the solute carrier superfamily and is highly expressed at the basolateral membrane of hepatocytes. Several clinical studies show drug-drug interactions involving OATP1B1, thereby prompting the International Transporter Consortium to label OATP1B1 as a critical transporter that can influence a compound's disposition. To examine OATP1B1 inhibition early in the drug discovery process, we established a medium-throughput concentration-dependent OATP1B1 assay.

Discovery of chiral dihydropyridopyrimidinones as potent, selective and orally bioavailable inhibitors of AKT.

During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK. A key challenge in this program was the poor physicochemical properties of the initial lead compound 5. Integration of structure-based drug design and physical properties-based design resulted in replacement of a highly hydrophobic poly fluorinated aryl ring by a simple trifluoromethyl that led to identification of compound 6 with much improved physicochemical properties.