Biochemische Analysen zur Funktion und Regulation von Cytohesin-1 in humanen T-Zellen

Die Integrinrezeptor-vermittelte Zelladhäsion wird durch intrazelluläre Signalkaskaden kontrolliert. Cytohesin-1 ist ein integrinbindendes Protein und ein Guanin-Nukleotid- Austauschfaktor (GEF). Dieser aktiviert das b2-Integrin LFA-1 und induziert dessen Bindung an ICAM-1. Cytohesin-1 enthält eine PH-Domäne, diese ist an der funktionalen Regulation des Proteins beteiligt und vermittelt die Membranrekrutierung über Phosphatidylinositol- (3,4,5)-trisphosphat, dem Produkt der Phosphatidylinositol-3-Kinase. Die Phosphoinositidvermittelte Membranbindung wird primär von der PH-Domäne bewirkt, jedoch wird diese Funktion von der carboxyterminalen polybasischen c-Domäne gestützt. In der vorliegenden Studie wurde gezeigt, daß ein Serin/Threonin-Motiv innerhalb dieser c-Domäne durch gereinigte PKCd in vitro und in vivo nach Phorbolesterstimulierung phosphoryliert wird. Biochemische und funktionale Analysen zeigten, daß phosphoryliertes Cytohesin-1 mit dem Aktinzytoskelett assoziiert. Weiterhin konnte gezeigt werden, daß durch Phosphorylierung von Cytohesin-1 der Guanin-Nukleotid-Austausch an ARF1 in vitro reguliert wird. ARF-Proteine sind entscheidend an der Zytoskelettreorganisation beteiligt, die während Zelladhäsionsprozessen stattfindet. In Zellen zeigte sich, daß die LFA-1-abhängige Zelladhäsion an ICAM-1 durch phosphoryliertes Cytohesin-1 drastisch gesteigert wird. Zusammengefaßt zeigen diese Erkenntnisse, daß intrazelluläre Signalkaskaden über Phosphatidylinositol-3-Kinase und Protein-Kinase-C in Cytohesin-1 als funktionalem Integrator münden. Cytohesin-1 reguliert über diese Prozesse die b2-Integrin-vermittelte Zelladhäsion von T-Lymphozyten

PLC-automata: a new class of implementable real-time automata

AbstractWe introduce PLC-automata as a new class of automata which are tailored to deal with real-time properties of programmable logic controllers (PLCs). These devices are often used in industrial practice to solve controlling problems. Nevertheless, PLC-automata are not restricted to PLCs, but can be seen as a model for all polling systems. A semantics in an appropriate real-time temporal logic (duration calculus) is given and an implementation schema that fits the semantics is presented in a programming language for PLCs. A case study is used to demonstrate the suitability of this approach. We define several parallel composition operators, and present an alternative semantics in terms of timed automata for which model-checkers are available

Solving Planning Problems Using RealTime Model-Checking (Translating PDDL3 into Timed Automata

We present a translation for the variant PDDL 3 of PDDL (Planning Domain Definition Language) into Timed Automata. The advantage of having such a translation is the availability of tool support by modelcheckers. We present a case study in which we apply a version of UPPAAL that has been extended for the search of cost-optimal solutions

Under consideration for publication in Formal Aspects of Computing Comparing Model-Checking and Logical Reasoning for Real-Time Systems

Abstract. We apply both model-checking and logical reasoning to a real-time protocol for mutual exclusion. To this end we employ PLC-Automata, an abstract notion of programs for real-time systems. A logic based semantics in terms of Duration Calculus is used to verify the correctness of the protocol by logical reasoning. An alternative but consistent operational semantics in terms of Timed Automata is used to verify the correctness by model-checkers. Since model-checking of the full model does not terminate in all cases within acceptable time we examine abstractions and their influence on model-checking performance. We present two abstraction methods that can be applied successfully for the protocol presented. 1

Heuristic Guided Model-Checking of Real-Time Systems ∗

We present an approach to model-check real-time systems by the cost-optimising version of Uppaal. The additional features for heuristic guidance of the cost-optimising version improve the performance in finding error traces. An important precondition for successful heuristics are contextual information about the system. To demonstrate our approach we introduce a mutual exclusion problem of a real-time system specified in terms of PLC-Automata. Finding errors by model-checking the semantics in terms of timed automata is substantially improved by heuristics guidance. Our heuristics are derived by exploiting the contextual information that the timed automata system to be checked represents the semantics of PLC-Automata.

Heuristic Guided Model-Checking of Real-Time Systems ⋆

Abstract. We present an approach to model-check real-time systems by the costoptimising version of Uppaal. The additional features for heuristic guidance of the cost-optimising version improve the performance in finding error traces. An important precondition for successful heuristics are contextual information about the system. To explain our approach we introduce a mutual exclusion problem of a real-time system specified in terms of PLC-Automata. Finding errors by modelchecking the semantics in terms of timed automata is substantially improved by heuristics guidance. Our heuristics are derived by exploiting the contextual information that the timed automata system to be checked represents the semantics of PLC-Automata. Finally we present the results of our approach applied to a non-trivial case study from an industrial project