SCFFBXW7 E3 ubiquitin ligase complex is a crucial enzyme of the ubiquitin proteasome system that participates in variant activities of cell process, and its component FBXW7 (F-box and WD repeat domain–containing 7) is responsible for recognizing and binding to substrates. The expression of FBXW7 is controlled by multiple pathways at different levels. FBXW7 facilitates the maturity and function maintenance of immune cells via functioning as a mediator of ubiquitination-dependent degradation of substrate proteins. FBXW7 deficiency or mutation results in the growth disturbance and dysfunction of immune cell, leads to the resistance against immunotherapy, and participates in multiple illnesses. It is likely that FBXW7 coordinating with its regulators and substrates could offer potential targets to improve the sensitivity and effects of immunotherapy. Here, we review the mechanisms of the regulation on FBXW7 and its tumor suppression role in immune filed among various diseases (mostly cancers) to explore novel immune targets and treatments.
The Split Hopkinson Tensile Bar (SHTB) is one of the most widely used methods to study the high strain rate behavior of materials. For these experiments usually dogbone-shaped sheet specimens are used. However, there’s no agreement on the exact dimensions. In the present study, mechanism of the influence of specimen responses on accuracy of SHTB experiments was investigated with finite element program ABAQUS (Explicit). Indicators which can evaluate the measurement accuracy of specimens are proposed based on this. Orthogonal test is designed to establish the sample database for back-propagation (BP) neural network, which is adopted to fit the non-linear mapping from structure parameters to accuracy indicators of specimen. Optimal design of structure for sheet specimen is obtained with Genetic Algorithm (GA) according to the fitness of individual determined by trained and qualified BP neural network. At last, numerical simulations are adopted to verify the validity of the optimal structure for sheet specimen. The result of this study can provide recommendations for specimen design and data reliability analysis in Split Hopkinson Tensile experiments.
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