Defect driven physics-informed neural network framework for fatigue life prediction of additively manufactured materials.

Additive manufacturing (AM) has attracted many attentions because of its design freedom and rapid manufacturing; however, it is still limited in actual application due to the existing defects. In particular, various defect features have been proved to affect the fatigue performance of components and lead to fatigue scatter. In order to properly assess the influences of these defect features, a defect driven physics-informed neural network (PiNN) is developed. By embedding the critical defects information into loss functions, the defect driven PiNN is enhanced to capture physical information during training progress. The results of fatigue life prediction for different AM materials show that the proposed PiNN effectively improves the generalization ability under small samples condition. Compared with the fracture mechanics-based PiNN, the proposed PiNN provides physically consistent and higher accuracy without depending on the choice of fracture mechanics-based model. Moreover, this work provides a scalable framework being able to integrate more prior knowledge into the proposed PiNN. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

N-Benzyl/Aryl Substituted Tryptanthrin as Dual Inhibitors of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase.

Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the same reaction and play a potential role in cancer immunotherapy. Starting from our previously discovered tryptanthrin IDO1 inhibitor scaffold, we synthesized novel N-benzyl/aryl substituted tryptanthrin derivatives and evaluated their inhibitory efficacy on IDO1, TDO, and IDO2. Most compounds showed similar high inhibitory activities on both IDO1 and TDO, which were significantly superior over that of IDO2 with magnitude difference. We showed that N-benzyl/aryl substituted tryptanthrin directly interacted with IDO1, TDO, and IDO2, significantly augmented the proliferation of T cells in vitro, blocked the kynurenine pathway, and suppressed tumor growth when administered to LLC and H22 tumor-bearing mice.