The healthiness of Australian food outlets available through online delivery platforms, by level of socioeconomic disadvantage and remoteness.

Online food delivery platforms are an emerging but poorly understood aspect of food retail environments. We collected data via web scraping methods from the two leading online food delivery platforms in Victoria, Australia, identifying 11,154 food outlets from Menulog, and 12,939 from Uber Eats (with 21,733 unique outlets available across both platforms). Outlets were classified according to their healthiness using a tool developed with Australian dietitians and public health nutritionists, and assigned a food environment score.

Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity.

To dissect variant-function relationships in the KRAS oncoprotein, we performed deep mutational scanning (DMS) screens for both wild-type and KRAS mutant alleles. We defined the spectrum of oncogenic potential for nearly all possible variants, identifying several novel transforming alleles and elucidating a model to describe the frequency of mutations in human cancer as a function of transforming potential, mutational probability, and tissue-specific mutational signatures. Biochemical and structural analyses of variants identified in a KRAS second-site suppressor DMS screen revealed that attenuation of oncogenic KRAS can be mediated by protein instability and conformational rigidity, resulting in reduced binding affinity to effector proteins, such as RAF and PI3-kinases, or reduced SOS-mediated nucleotide exchange activity.

BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.

The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition.

The laser pump X-ray probe system at LISA P08 PETRA III.

Understanding and controlling the structure and function of liquid interfaces is a constant challenge in biology, nanoscience and nanotechnology, with applications ranging from molecular electronics to controlled drug release. X-ray reflectivity and grazing incidence diffraction provide invaluable probes for studying the atomic scale structure at liquid-air interfaces. The new time-resolved laser system at the LISA liquid diffractometer situated at beamline P08 at the PETRA III synchrotron radiation source in Hamburg provides a laser pump with X-ray probe.

Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory, and Antioxidant Properties.

This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds -, via a convenient one-pot three-component Hantzsch reaction.