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The manufacturing industry has identified a new megatrend of mass customization, which is one of the essential goals of Industry 4.0. This megatrend requires the realization of manufacturing that can respond quickly and flexibly to various changing production requirements and ensure the achievement of various quality criteria. However, the manufacturing cannot be realized by conventional manufacturing systems in which reconfigurations need to be performed by skilled engineers. This paper proposes a new reconfigurable manufacturing system concept based on an ultra-flexible transfer system. Particularly, an autonomous mobile robotic manipulator, consisting of a high-performance automated guided vehicle module and a collaborative robotic manipulator module, represents a key component of the system concept. In this context, the focus is on the cooperative control between the modules of the autonomous mobile manipulator, which is essential for high-precision processes (e.g., machining, assembly, measurement, inspection), and its wide operating area. The experimental results confirm that the proposed cooperative control improves the positioning performance of the autonomous mobile manipulator, including the time required for positioning and the positioning accuracy. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor, is required for lymphocyte trafficking, and is a promising therapeutic target in inflammatory diseases. Here, we synthesize a competitive S1PR1 antagonist, KSI-6666, that effectively suppresses pathogenic inflammation. Metadynamics simulations suggest that the interaction of KSI-6666 with a methionine residue Met124 in the ligand-binding pocket of S1PR1 may inhibit the dissociation of KSI-6666 from S1PR1. Consistently, in vitro functional and mutational analyses reveal that KSI-6666 causes pseudoirreversible inhibition of S1PR1, dependent on the Met124 of the protein and substituents on the distal benzene ring of KSI-6666. Moreover, in vivo study suggests that this pseudoirreversible inhibition is responsible for the persistent activity of KSI-6666., (© 2024. The Author(s).)