A Metaheuristic Framework for Bi-level Programming Problems with Multi-disciplinary Applications

Bi-level programming problems arise in situations when the decision maker has to take into account the responses of the users to his decisions. Several problems arising in engineering and economics can be cast within the bi-level programming framework. The bi-level programming model is also known as a Stackleberg or leader-follower game in which the leader chooses his variables so as to optimise his objective function, taking into account the response of the follower(s) who separately optimise their own objectives, treating the leader’s decisions as exogenous. In this chapter, we present a unified framework fully consistent with the Stackleberg paradigm of bi-level programming that allows for the integration of meta-heuristic algorithms with traditional gradient based optimisation algorithms for the solution of bi-level programming problems. In particular we employ Differential Evolution as the main meta-heuristic in our proposal.We subsequently apply the proposed method (DEBLP) to a range of problems from many fields such as transportation systems management, parameter estimation and game theory. It is demonstrated that DEBLP is a robust and powerful search heuristic for this class of problems characterised by non smoothness and non convexity

Saccharomyces cerevisiae Ccr4–Not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway

The Ccr4–Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to modulate the activity of TFIID. In the present work, we provide evidence that the Ccr4–Not complex may contribute to transcriptional regulation by the Ras/cAMP pathway. Several observations support this model. First, Msn2/4p-dependent transcription, which is known to be under negative control of cAMP-dependent protein kinase (PKA), is derepressed in all ccr4–not mutants. This phenotype is paralleled by specific post-translational modification defects of Msn2p in ccr4–not mutants relative to wild-type cells. Secondly, mutations in various NOT genes result in a synthetic temperature-sensitive growth defect when combined with mutations that compromise cells for PKA activity and at least partially suppress the effects of both a dominant-active RAS2Val-19 allele and loss of Rim15p. Thirdly, Not3p and Not5p, which are modified and subsequently degraded by stress signals that also lead to increased Msn2/4p-dependent activity, show a specific twohybrid interaction with Tpk2p. Together, our results suggest that the Ccr4–Not complex may function as an effector of the Ras/cAMP pathway that contributes to repress basal, stress- and starvation-induced transcription by Msn2/4p