Time-Staging Enhancement of Hybrid System Falsification

Optimization-based falsification employs stochastic optimization algorithms to search for error input of hybrid systems. In this paper we introduce a simple idea to enhance falsification, namely time staging, that allows the time-causal structure of time-dependent signals to be exploited by the optimizers. Time staging consists of running a falsification solver multiple times, from one interval to another, incrementally constructing an input signal candidate. Our experiments show that time staging can dramatically increase performance in some realistic examples. We also present theoretical results that suggest the kinds of models and specifications for which time staging is likely to be effective

A bidirectional fluorescent two-hybrid system for monitoring protein–protein interactions

Two-hybrid systems have been the cornerstone of research into protein–protein interactions, but these systems typically rely on life/death reporters that put additional selective pressure on the host organism, and potentially lead to false positives. Here we report a bidirectional fluorescence-based bacterial two- hybrid system that enables both the association and dissociation of a given protein–protein interaction to be monitored. The functionality of this system and its compatibility with FACS screening are demon- strated in the forward and reverse direction using known interacting protein-partners and their cyclic peptide inhibitors. The reported fluorescent two-hybrid system may be used in the forward direction for the identification of interacting protein partners, or as a reverse two-hybrid system for the high- throughput identification of protein–protein interaction inhibitors