Ultrasonic monitoring of recrystallization: an example of in-situ process control with NDE

Technology development in materials science, electrical engineering, NDE, mechanical engineering, and computer science, makes it possible to produce advanced materials of designed microstructure and properties. A control model for materials processing with NDE technology was proposed and a prototype of the high temperature EMAT measurement system was built. The example studied is the ultrasonic monitoring of recrystallization in 5XXX aluminum alloys. There are two distinguished textures in aluminum alloys, i.e., recrystallization texture and rolling texture. These two textures change in opposite directions during the hot rolling process: the rolling process will produce rolling texture, while the annealing process produces recrystallization texture. The control goal of the hot rolling process is to produce predefined texture and microstructure. Texture information is inferred from ultrasonic velocity measurements and the microstructure information is inferred from ultrasonic attenuation measurements. Several models in interdisciplinary fields are proposed and preliminary verification experimental results were presented. A pattern recognition technique was introduced to process OIM raw data, which results in a new algorithm to extract texture information. A new model was proposed to model the texture evolution during annealing. Several pieces of computer software were developed to process experimental data and to implement the models proposed

Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy

T cells play a critical role in antitumor immunity, where T cell activation is regulated by both inhibitory and costimulatory receptor signaling that fine-tune T cell activity during different stages of T cell immune responses. Currently, cancer immunotherapy by targeting inhibitory receptors such as CTLA-4 and PD-1/L1, and their combination by antagonist antibodies, has been well established. However, developing agonist antibodies that target costimulatory receptors such as CD28 and CD137/4-1BB has faced considerable challenges, including highly publicized adverse events. Intracellular costimulatory domains of CD28 and/or CD137/4-1BB are essential for the clinical benefits of FDA-approved chimeric antigen receptor T cell (CAR-T) therapies. The major challenge is how to decouple efficacy from toxicity by systemic immune activation. This review focuses on anti-CD137 agonist monoclonal antibodies with different IgG isotypes in clinical development. It discusses CD137 biology in the context of anti-CD137 agonist drug discovery, including the binding epitope selected for anti-CD137 agonist antibody in competition or not with CD137 ligand (CD137L), the IgG isotype of antibodies selected with an impact on crosslinking by Fc gamma receptors, and the conditional activation of anti-CD137 antibodies for safe and potent engagement with CD137 in the tumor microenvironment (TME). We discuss and compare the potential mechanisms/effects of different CD137 targeting strategies and agents under development and how rational combinations could enhance antitumor activities without amplifying the toxicity of these agonist antibodies