Drivers\u27 Ability to Engage in a Non-Driving Related Task While in Automated Driving Mode in Real Traffic

Engaging in non-driving related tasks (NDRTs) while driving can be considered distracting and safety detrimental. However, with the introduction of highly automated driving systems that relieve drivers from driving, more NDRTs will be feasible. In fact, many car manufacturers emphasize that one of the main advantages with automated cars is that it "frees up time" for other activities while on the move. This paper investigates how well drivers are able to engage in an NDRT while in automated driving mode (i.e., SAE Level 4) in real traffic, via a Wizard of Oz platform. The NDRT was designed to be visually and cognitively demanding and require manual interaction. The results show that the drivers\u27 attention to a great extent shifted from the road ahead towards the NDRT. Participants could perform the NDRT equally well as when in an office (e.g. correct answers, time to completion), showing that the performance did not deteriorate when in the automated vehicle. Yet, many participants indicated that they noted and reacted to environmental changes and sudden changes in vehicle motion. Participants were also surprised by their own ability to, with ease, disconnect from driving. The presented study extends previous research by identifying that drivers to a high extent are able to engage in a NDRT while in automated mode in real traffic. This is promising for future of automated cars ability to "free up time" and enable drivers to engage in non-driving related activities

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo