Cyber-physical systems (CPSs) are naturally highly interconnected and complexly nonlinear. This paper investigates the problem of decentralized adaptive output feedback control for CPSs subject to intermittent denial-of-service (DoS) attacks. The considered CPSs are modeled as a class of nonlinear uncertain strict-feedback interconnected systems. When a DoS attack is active, all the state variables become unavailable and standard backstepping cannot be applied. To overcome this difficulty, a switching-type adaptive state estimator is constructed. Based on an improved average dwell time method incorporated by frequency and duration properties of DoS attacks, convex design conditions of controller parameters are derived in term of solving a set of linear matrix inequalities. The proposed controller guarantees that all closed-loop signals remain bounded, while the error signals converge to a small neighborhood of the origin. As an illustrative example, the proposed control scheme is applied to a power network system.
Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation. We also identified STRN3 upregulation in gastric cancer correlated with YAP activation and poor prognosis. Based on this mechanistic understanding and aided by structure-guided medicinal chemistry, we developed a highly selective peptide inhibitor, STRN3-derived Hippo-activating peptide, or SHAP, which disrupts the STRN3-PP2Aa interaction and reactivates the Hippo tumor suppressor, inhibits YAP activation, and has antitumor effects in vivo.
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