A Comparison of Ultrasonics and Radiography for Weld Inspection

Since the 1940’s, the accepted inspection method for structural welds in the U.S. Navy has been radiography (RT). This technique has been accepted as an inspection method for welds since the 1940’s. A major advantage of radiography compared to other inspection techniques is the availability of objective quality evidence, the radiograph, as a permanent record of the inspection. Radiography has gained precedence as the inspection method to prescribe for these welds because this permanent record is perceived to evince all discontinuities and facilitates auditing. This technique and the criteria used to accept or reject discontinuities have generally proved adequate although technical limitations and cost disadvantages have been encountered

Small molecule inhibitors of PD 1 PD L1 immune checkpoint alleviate the PD L1 induced exhaustion of T cells

Antibodies targeting the PD-1/PD-L1 immune checkpoint achieved spectacular success in anticancer therapy in the recent years. In contrast, no small molecules with cellular activity have been reported so far. Here we provide evidence that small molecules are capable of alleviating the PD-1/PD-L1 immune checkpoint-mediated exhaustion of Jurkat T-lymphocytes. The two optimized small-molecule inhibitors of the PD-1/PD-L1 interaction, BMS-1001 and BMS-1166, developed by Bristol-Myers Squibb, bind to human PD-L1 and block its interaction with PD-1, when tested on isolated proteins. The compounds present low toxicity towards tested cell lines and block the interaction of soluble PD-L1 with the cell surface-expressed PD-1. As a result, BMS-1001 and BMS-1166 alleviate the inhibitory effect of the soluble PD-L1 on the T-cell receptor-mediated activation of T-lymphocytes. Moreover, the compounds were effective in attenuating the inhibitory effect of the cell surface-associated PD-L1. We also determined the X-ray structures of the complexes of BMS-1001 and BMS-1166 with PD-L1, which revealed features that may be responsible for increased potency of the compounds compared to their predecessors. Further development may lead to the design of an anticancer therapy based on the orally delivered immune checkpoint inhibition