McStas (ii): An overview of components, their use, and advice for user contributions

A key element of the success of McStas is the component layer where users and developers alike are contributing to the description of new physical models and features. In McStas, components realise all physical elements of the simulated instrument from source via optics and samples to detector. In this second review paper of the McStas package, we present an overview of the component classes in McStas: sources, monitors, optics, samples, misc, and contrib. Within each component class we give thorough examples of high-quality components, including their algorithms and example use. We present two example instruments, one for a continuous source and one for a time-of-flight source, that together demonstrate the use of the main component classes. Finally, we give tips and instructions that will allow the reader to write good components and elucidate the pathway of contributing new components to McStas.

CRISPR-Cas3 induces broad and unidirectional genome editing in human cells

Although single-component Class 2 CRISPR systems, such as type II Cas9 or type V Cas12a (Cpf1), are widely used for genome editing in eukaryotic cells, the application of multi-component Class 1 CRISPR has been less developed. Here we demonstrate that type I-E CRISPR mediates distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5′-ARG protospacer adjacent motif (PAM), without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation can be used to introduce functional gene knockouts and knock-ins. As an example of potential therapeutic applications, we show Cas3-mediated exon-skipping of the Duchenne muscular dystrophy (DMD) gene in patient-induced pluripotent stem cells (iPSCs). These findings broaden our understanding of the Class 1 CRISPR system, which may serve as a unique genome editing tool in eukaryotic cells distinct from the Class 2 CRISPR system.

On the Primary Importance of Pulsars with Five-Component Profiles

Some 15 members of the class of profiles with five components have been identified. These profiles have a central core component and two pairs of conal outriders, thus exhibiting the highest degree of formal complexity observed. No good examples of pulsars with six or more profile components are known.Members of the five-component class have very similar physical parameters and emission-region geometries. An analysis of their emission geometry indicates both that the core and conal beams scale as P–1/2 and that the 1-GHz conal emission comes from a height of some 100-200 km.