Institut für Informatik und Computational Science
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Secondary activation of the endothelin system is thought to be involved in toxic liver injury. This study tested the hypothesis that dual endothelin-converting enzyme / neutral endopeptidase blockade might: be able to attenuate acute toxic liver injury.
Male Sprague-Dawley rats were implanted with subcutaneous minipumps to deliver the novel compound SLV338 (10 mg/kg*d) or vehicle. Four days later they received two intraperitoneal injections of D-galactosamine (1.3 g/kg each) or vehicle at an interval of 12 hours. The animals were sacrificed 48 hours after the first injection.
Injection of D-galactosamine resulted in very severe liver injury, reflected by strongly elevated plasma liver enzymes, hepatic necrosis and inflammation, and a mortality rate of 42.9 %. SLV338 treatment did not show any significant effect on the extent of acute liver injury as judged from plasma parameters, hepatic histology and mortality. Plasma measurements of SLV338 confirmed adequate drug delivery. Plasma concentrations of big endothelin-1 and endothelin-1 were significantly elevated in animals with liver injury (5-fold and 62-fold, respectively). Plasma endothelin-1 was significantly correlated with several markers of liver injury. SLV338 completely prevented the rise of plasma big endothelin-1 (p<0.05) and markedly attenuated the rise of endothelin-1 (p = 0.055).
In conclusion, dual endothelin-converting enzyme / neutral endopeptidase blockade by SLV338 did not significantly attenuate D-galactosamine-induced acute liver injury, although it largely prevented the activation of the endothelin system. An evaluation of SLV338 in a less severe model of liver injury would be of interest, since very severe intoxication might not be relevantly amenable to pharmacological interventions.
Engineering of process-driven business applications can be supported by process modeling efforts in order to bridge the gap between business requirements and system specifications. However, diverging purposes of business process modeling initiatives have led to significant problems in aligning related models at different abstract levels and different perspectives. Checking the consistency of such corresponding models is a major challenge for process modeling theory and practice. In this paper, we take the inappropriateness of existing strict notions of behavioral equivalence as a starting point. Our contribution is a concept called behavioral profile that captures the essential behavioral constraints of a process model. We show that these profiles can be computed efficiently, i.e., in cubic time for sound free-choice Petri nets w.r.t. their number of places and transitions. We use behavioral profiles for the definition of a formal notion of consistency which is less sensitive to model projections than common criteria of behavioral equivalence and allows for quantifying deviation in a metric way. The derivation of behavioral profiles and the calculation of a degree of consistency have been implemented to demonstrate the applicability of our approach. We also report the findings from checking consistency between partially overlapping models of the SAP reference model.
Behavioral models capture operational principles of real-world or designed systems. Formally, each behavioral model defines the state space of a system, i.e., its states and the principles of state transitions. Such a model is the basis for analysis of the system's properties. In practice, state spaces of systems are immense, which results in huge computational complexity for their analysis. Behavioral models are typically described as executable graphs, whose execution semantics encodes a state space. The structure theory of behavioral models studies the relations between the structure of a model and the properties of its state space. In this article, we use the connectivity property of graphs to achieve an efficient and extensive discovery of the compositional structure of behavioral models; behavioral models get stepwise decomposed into components with clear structural characteristics and inter-component relations. At each decomposition step, the discovered compositional structure of a model is used for reasoning on properties of the whole state space of the system. The approach is exemplified by means of a concrete behavioral model and verification criterion. That is, we analyze workflow nets, a well-established tool for modeling behavior of distributed systems, with respect to the soundness property, a basic correctness property of workflow nets. Stepwise verification allows the detection of violations of the soundness property by inspecting small portions of a model, thereby considerably reducing the amount of work to be done to perform soundness checks. Besides formal results, we also report on findings from applying our approach to an industry model collection.
Automatic code generation is an essential cornerstone of today's model-driven approaches to software engineering. Thus a key requirement for the success of this technique is the reliability and correctness of code generators. This article describes how we employ standard model checking-based verification to check that code generator models developed within our code generation framework Genesys conform to (temporal) properties. Genesys is a graphical framework for the high-level construction of code generators on the basis of an extensible library of well-defined building blocks along the lines of the Extreme Model-Driven Development paradigm. We will illustrate our verification approach by examining complex constraints for code generators, which even span entire model hierarchies. We also show how this leads to a knowledge base of rules for code generators, which we constantly extend by e.g. combining constraints to bigger constraints, or by deriving common patterns from structurally similar constraints. In our experience, the development of code generators with Genesys boils down to re-instantiating patterns or slightly modifying the graphical process model, activities which are strongly supported by verification facilities presented in this article.
In this paper we consider masking of unknowns (X-values) for VLSI circuits. We present a new hierarchical method of X-masking which is a major improvement of the method proposed in [4], called WIDE1. By the method proposed, the number of observable scan cells is optimized and data volume for X-masking can be significantly reduced in comparison to WIDEL This is demonstrated for three industrial designs. In cases where all X-values have to be masked the novel approach is especially efficient.
We investigate the decidability of the operation problem for TOL languages and subclasses. Fix an operation on formal languages. Given languages from the family considered (OL languages, TOL languages, or their propagating variants), is the application of this operation to the given languages still a language that belongs to the same language family? Observe, that all the Lindenmayer language families in question are anti-AFLs, that is, they are not closed under homomorphisms, inverse homomorphisms, intersection with regular languages, union, concatenation, and Kleene closure. Besides these classical operations we also consider intersection and substitution, since the language families under consideration are not closed under these operations, too. We show that for all of the above mentioned language operations, except for the Kleene closure, the corresponding operation problems of OL and TOL languages and their propagating variants are not even semidecidable. The situation changes for unary OL languages. In this case we prove that the operation problems with respect to Kleene star, complementation, and intersection with regular sets are decidable.