Previous work from this laboratory suggests an activation of the sphingomyelin cycle as a mechanism for growth inhibition with the incorporation of beta-sitosterol (SIT) into human prostate cancer LNCaP cells. In the present study we examined two key enzymes that have been shown to play a role in the sphingomyelin cycle. Dietary sterols (SIT and cholesterol) were compared for their effect on LNCaP cell growth, phospholipase D (PLD) activity, and protein phosphatase 2A (PP 2A) activity and expression. PP 2A has been suggested as a direct in vitro target of ceramide action on cell growth and apoptosis. Ceramide also inhibits phorbol myristate acetate-stimulated PLD. SIT (16 microM) increased PP 2A activity by 50% compared with cholesterol treatment in LNCaP prostate cells; however, SIT did not alter protein levels of PP 2A. There was an increase in PLD activity in the presence of phorbol myristate acetate in cells supplemented with 16 microM SIT compared with those supplemented with cholesterol after five days of treatment. The present study suggests that the activation of PP 2A added support to the role of the activation of the sphingomyelin cycle by SIT treatment. However, the increase in PLD activity, which was modest but significant, with SIT supplementation suggests that this pathway may be modulated by other mechanisms. This includes the incorporation of SIT into cell membranes that may alter fluidity and, thus, influence the activation of membrane-bound enzymes such as PLD.

We study supervisor localization for real-time discrete-event systems (DES) in the Brandin-Wonham framework of timed supervisory control. We view a real-time DES as comprised of asynchronous agents which are coupled through imposed logical and temporal specifications; the essence of supervisor localization is the decomposition of monolithic (global) control action into local control strategies for these individual agents. This study extends our previous work on supervisor localization for untimed DES, in that monolithic timed control action typically includes not only disabling action as in the untimed case, but also "clock preempting" action which enforces prescribed temporal behavior. The latter action is executed by a class of special events, called "forcible" events; accordingly, we localize monolithic preemptive action with respect to these events. We demonstrate the new features of timed supervisor localization with a manufacturing cell case study, and discuss a distributed control implementation.

This paper identifies a property of delay-robustness in distributed supervisory control of discrete-event systems (DES) with communication delays. In previous work a distributed supervisory control problem has been investigated on the assumption that inter-agent communications take place with negligible delay. From an applications viewpoint it is desirable to relax this constraint and identify communicating distributed controllers which are delay-robust, namely logically equivalent to their delay-free counterparts.For this we introduce inter-agent channels modeled as 2-state automata, compute the overall system behavior, and present an effective computational test for delay-robustness. From the test it typically results that the given delay-free distributed control is delay-robust with respect to certain communicated events, but not for all, thus distinguishing events which are not delay-critical from those that are. The approach is illustrated by a workcell model with three communicating agents.

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Much research has been addressed to nonblocking supervisory control of Discrete-Event Systems (DES) such as Flexible Manufacturing Systems (FMS), and a variety of approaches have been developed. One especially powerful approach, due to Chuan Ma, is based on DES representation by means of State Tree Structures (STS). Using STS, this chapter develops nonblocking supervisory control of a well-known benchmark FMS example taken from the literature, for which the description was given originally as a Petri net. The authors straightforwardly obtain the optimal (maximally permissive) and nonblocking supervisory control, and display the control logic for each (controllable) event transparently as a binary decision diagram.

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