Ultrafast Single-Particle Imaging with Intense X-Ray Pulses

Ultrafast single-particle imaging with intense x-ray pulses from free-electron laser sources provides a new approach for visualizing structure and dynamics on the nanoscale. After a short introduction to the novel free-electron laser sources and methods, we highlight selected applications and discuss how ultrafast imaging flourishes from method development to early applications in physics and biology to opportunities for chemical sciences

Knowledge bases and software support for variant interpretation in precision oncology

Precision oncology is a rapidly evolving interdisciplinary medical specialty. Comprehensive cancer panels are becoming increasingly available at pathology departments worldwide, creating the urgent need for scalable cancer variant annotation and molecularly informed treatment recommendations. A wealth of mainly academia-driven knowledge bases calls for software tools supporting the multi-step diagnostic process. We derive a comprehensive list of knowledge bases relevant for variant interpretation by a review of existing literature followed by a survey among medical experts from university hospitals in Germany. In addition, we review cancer variant interpretation tools, which integrate multiple knowledge bases. We categorize the knowledge bases along the diagnostic process in precision oncology and analyze programmatic access options as well as the integration of knowledge bases into software tools. The most commonly used knowledge bases provide good programmatic access options and have been integrated into a range of software tools. For the wider set of knowledge bases, access options vary across different parts of the diagnostic process. Programmatic access is limited for information regarding clinical classifications of variants and for therapy recommendations. The main issue for databases used for biological classification of pathogenic variants and pathway context information is the lack of standardized interfaces. There is no single cancer variant interpretation tool that integrates all identified knowledge bases. Specialized tools are available and need to be further developed for different steps in the diagnostic process

Widely tunable two-color x-ray free-electron laser pulses

We demonstrate the generation of widely tunable two-color x-ray free-electron laser (FEL) pulses at SwissFEL. In a split-undulator configuration, each color is produced in a different undulator section, and a chicane between the two sections allows for a variable time separation between the two pulses of up to 500 fs. We show an unprecedented photon energy ratio between the two colors of about three (350 and 915 eV), with each individual pulse having a peak power of a few gigawatts and a duration down to the femtosecond level. Moreover, we demonstrate the reduction of the required undulator length via the optical klystron mechanism and the time-resolved diagnostics of the FEL pulses utilizing the same beam setup as for the pulse generation. The unique combination of widely tunable energy and time separation of the two-color pulse pair offers opportunities to study ultrafast x-ray-induced energy transfer and relaxation processes in physics, chemistry, and biology.ISSN:2643-156