Deep Impact? On 15 February 2013, the Russian district of Chelyabinsk, with a population of more than 1 million, suffered the impact and atmospheric explosion of a 20-meter-wide asteroid—the largest impact on Earth by an asteroid since 1908. Popova et al. (p. 1069 , published online 7 November; see the Perspective by Chapman ) provide a comprehensive description of this event and of the body that caused it, including detailed information on the asteroid orbit and atmospheric trajectory, damage assessment, and meteorite recovery and characterization.

A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC(50) value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance.

The surface condition of a sample mount is an important factor influencing the precision of SIMS isotope analysis. The phenomenon that the sample topography affects the analytical precision is called the topography effect. We carried out a systematic experiment of O-isotope analyses using a Cameca IMS-1280 SIMS to quantitatively characterize the topography effect with the aim of better understanding its physical mechanism underlying such an artifact and ultimately improving the analytical precision. Our results indicate that within a mineral grain, the topography effect is obvious in the X-direction (horizontal direction) of the sample stage but insignificant in the Y-direction (vertical direction). In addition, within a single mineral grain, the topography effect creates analytical spots on the left rim (lower X-coordinates) yielding higher measured d 18 O values than those on the right rim (higher X-coordinates) in our instrument. The physical reason that the topography effect compromises the analytical reproducibility is attributed to lateral energy dispersion of secondary ions caused by surface topography changing the ion position in the entrance slit plane. By increasing the transfer optics magnification, the topography effect could be significantly reduced. Beam centering parameters could be used to quantitatively assess the topography effect and improve the data quality.