Cascading Failure in Cyber-Physical Systems: A Review on Failure Modeling and Vulnerability Analysis.

Cascading failures pose a significant security threat to networked systems, with recent global incidents underscoring their destructive potential. The security threat of cascading failures has always existed, but the evolution of cyber-physical systems (CPSs) has introduced novel dimensions to cascading failures, intensifying their threats owing to the intricate fusion of cyber and physical domains. Addressing these threats requires a nuanced understanding achieved through failure modeling and vulnerability analysis. By analyzing the historical failures in different CPSs, the cascading failure in CPSs is comprehensively defined as a complicated propagation process in coupled cyber and physical systems, initialized by natural accidents or human interference, which exhibits a progressive evolution within the networked structure and ultimately results in unexpected large-scale systemic failures. Subsequently, this study advances the development of instructions for modeling cascading failures and conducting vulnerability analyses within CPSs. The examination also delves into the core challenges inherent in these methodologies. Moreover, a comprehensive survey and classification of extant research methodologies and solutions are undertaken, accompanied by a concise evaluation of their advancements and limitations. To validate the performance of these methodologies, numerical experiments are conducted to ascertain their distinct features. In conclusion, this article advocates for future research initiatives, particularly emphasizing the exploration of uncertainty analysis, defense strategies, and verification platforms. By addressing these areas, the resilience of CPSs against cascading failures can be significantly enhanced.

Capturing acyl-enzyme intermediates with genetically encoded 2,3-diaminopropionic acid for hydrolase substrate identification.

Catalytic mechanism-based, light-activated traps have recently been developed to identify the substrates of cysteine or serine hydrolases. These traps are hydrolase mutants whose catalytic cysteine or serine are replaced with genetically encoded 2,3-diaminopropionic acid (DAP). DAP-containing hydrolases specifically capture the transient thioester- or ester-linked acyl-enzyme intermediates resulting from the first step of the proteolytic reaction as their stable amide analogs. The trapped substrate fragments allow the downstream identification of hydrolase substrates by mass spectrometry and immunoblotting. In this protocol, we provide a detailed step-by-step guide for substrate capture and identification of the peptidase domain of the large tegument protein deneddylase (UL36USP) from human herpesvirus 1, both in mammalian cell lysate and live mammalian cells. Four procedures are included: Procedure 1, DAP-mediated substrate trapping in mammalian cell lysate (~8 d); Procedure 2, DAP-mediated substrate trapping in adherent mammalian cells (~6 d); Procedure 3, DAP-mediated substrate trapping in suspension mammalian cells (~5 d); and Procedure 4, substrate identification and validation (~12-13 d). Basic skills to perform protein expression in bacteria or mammalian cells, affinity enrichment and proteomic analysis are required to implement the protocol. This protocol will be a practical guide for identifying substrates of serine or cysteine hydrolases either in a complex mixture, where genetic manipulation is challenging, or in live cells such as bacteria, yeasts and mammalian cells.