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.
Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.
Using the notion of an elementary loop, Gebser and Schaub (2005. Proceedings of the Eighth International Conference on Logic Programming and Nonmonotonic Reasoning (LPNMR'05), 53-65) refined the theorem on loop formulas attributable to Lin and Zhao (2004) by considering loop formulas of elementary loops only. In this paper, we reformulate the definition of an elementary loop, extend it to disjunctive programs, and study several properties of elementary loops, including how maximal elementary loops are related to minimal unfounded sets. The results provide useful insights into the stable model semantics in terms of elementary loops. For a nondisjunctive program, using a graph-theoretic characterization of an elementary loop, we show that the problem of recognizing an elementary loop is tractable. On the other hand, we also show that the corresponding problem is coNP-complete for a disjunctive program. Based on the notion of an elementary loop, we present the class of Head-Elementary-loop-Free (HEF) programs, which strictly generalizes the class of Head-Cycle-Free (HCF) programs attributable to Ben-Eliyahu and Dechter (1994. Annals of Mathematics and Artificial Intelligence 12, 53-87). Like an Ha: program, an HEF program can be turned into an equivalent nondisjunctive program in polynomial time by shifting head atoms into the body.
Parallel communicating finite automata (PCFAs) are systems of several finite state automata which process a common input string in a parallel way and are able to communicate by sending their states upon request. We consider deterministic and nondeterministic variants and distinguish four working modes. It is known that these systems in the most general mode are as powerful as one-way multi-head finite automata. It is additionally known that the number of heads corresponds to the number of automata in PCFAs in a constructive way. Thus, undecidability results as well as results on the hierarchies induced by the number of heads carry over from multi-head finite automata to PCFAs in the most general mode. Here, we complement these undecidability and hierarchy results also for the remaining working modes. In particular, we show that classical decidability questions are not semi-decidable for any type of PCFAs under consideration. Moreover, it is proven that the number of automata in the system induces infinite hierarchies for deterministic and nondeterministic PCFAs in three working modes.
Autonomy is an emerging paradigm for the design and implementation of managed services and systems. Self-managed aspects frequently concern the communication of systems with their environment. Self-management subsystems are critical, they should thus be designed and implemented as high-assurance components. Here, we propose to use GEAR, a game-based model checker for the full modal mu-calculus, and derived, more user-oriented logics, as a user friendly tool that can offer automatic proofs of critical properties of such systems. Designers and engineers can interactively investigate automatically generated winning strategies resulting from the games, this way exploring the connection between the property, the system, and the proof. The benefits of the approach are illustrated on a case study that concerns the ExoMars Rover.
We define and study quantum cellular automata (QCA). We show that they are reversible and that the neighborhood of the inverse is the opposite of the neighborhood. We also show that QCA always admit, modulo shifts, a two-layered block representation. Note that the same two-layered block representation result applies also over infinite configurations, as was previously shown for one-dimensional systems in the more elaborate formalism of operators algebras [18]. Here the proof is simpler and self-contained, moreover we discuss a counterexample QCA in higher dimensions.
Design thinking research
(2011)
Tele-board : enabling efficient collaboration in digital design spaces across time and distance
(2011)
One of the goals of artificial intelligence is to develop agents that learn and act in complex environments. Realistic environments typically feature a variable number of objects, relations amongst them, and non-deterministic transition behavior. While standard probabilistic sequence models provide efficient inference and learning techniques for sequential data, they typically cannot fully capture the relational complexity. On the other hand, statistical relational learning techniques are often too inefficient to cope with complex sequential data. In this paper, we introduce a simple model that occupies an intermediate position in this expressiveness/efficiency trade-off. It is based on CP-logic (Causal Probabilistic Logic), an expressive probabilistic logic for modeling causality. However, by specializing CP-logic to represent a probability distribution over sequences of relational state descriptions and employing a Markov assumption, inference and learning become more tractable and effective. Specifically, we show how to solve part of the inference and learning problems directly at the first-order level, while transforming the remaining part into the problem of computing all satisfying assignments for a Boolean formula in a binary decision diagram. We experimentally validate that the resulting technique is able to handle probabilistic relational domains with a substantial number of objects and relations.
We introduce hierarchical kFOIL as a simple extension of the multitask kFOIL learning algorithm. The algorithm first learns a core logic representation common to all tasks, and then refines it by specialization on a per-task basis. The approach can be easily generalized to a deeper hierarchy of tasks. A task clustering algorithm is also proposed in order to automatically generate the task hierarchy. The approach is validated on problems of drug-resistance mutation prediction and protein structural classification. Experimental results show the advantage of the hierarchical version over both single and multi task alternatives and its potential usefulness in providing explanatory features for the domain. Task clustering allows to further improve performance when a deeper hierarchy is considered.
Building biological models by inferring functional dependencies from experimental data is an important issue in Molecular Biology. To relieve the biologist from this traditionally manual process, various approaches have been proposed to increase the degree of automation. However, available approaches often yield a single model only, rely on specific assumptions, and/or use dedicated, heuristic algorithms that are intolerant to changing circumstances or requirements in the view of the rapid progress made in Biotechnology. Our aim is to provide a declarative solution to the problem by appeal to Answer Set Programming (ASP) overcoming these difficulties. We build upon an existing approach to Automatic Network Reconstruction proposed by part of the authors. This approach has firm mathematical foundations and is well suited for ASP due to its combinatorial flavor providing a characterization of all models explaining a set of experiments. The usage of ASP has several benefits over the existing heuristic algorithms. First, it is declarative and thus transparent for biological experts. Second, it is elaboration tolerant and thus allows for an easy exploration and incorporation of biological constraints. Third, it allows for exploring the entire space of possible models. Finally, our approach offers an excellent performance, matching existing, special-purpose systems.
Indoor position estimation constitutes a central task in home-based assisted living environments. Such environments often rely on a heterogeneous collection of low-cost sensors whose diversity and lack of precision has to be compensated by advanced techniques for localization and tracking. Although there are well established quantitative methods in robotics and neighboring fields for addressing these problems, they lack advanced knowledge representation and reasoning capacities. Such capabilities are not only useful in dealing with heterogeneous and incomplete information but moreover they allow for a better inclusion of semantic information and more general homecare and patient-related knowledge. We address this problem and investigate how state-of-the-art localization and tracking methods can be combined with Answer Set Programming, as a popular knowledge representation and reasoning formalism. We report upon a case-study and provide a first experimental evaluation of knowledge-based position estimation both in a simulated as well as in a real setting.
We introduce an approach to detecting inconsistencies in large biological networks by using answer set programming. To this end, we build upon a recently proposed notion of consistency between biochemical/genetic reactions and high-throughput profiles of cell activity. We then present an approach based on answer set programming to check the consistency of large-scale data sets. Moreover, we extend this methodology to provide explanations for inconsistencies by determining minimal representations of conflicts. In practice, this can be used to identify unreliable data or to indicate missing reactions.
Preference handling and optimization are indispensable means for addressing nontrivial applications in Answer Set Programming (ASP). However, their implementation becomes difficult whenever they bring about a significant increase in computational complexity. As a consequence, existing ASP systems do not offer complex optimization capacities, supporting, for instance, inclusion-based minimization or Pareto efficiency. Rather, such complex criteria are typically addressed by resorting to dedicated modeling techniques, like saturation. Unlike the ease of common ASP modeling, however, these techniques are rather involved and hardly usable by ASP laymen. We address this problem by developing a general implementation technique by means of meta-prpogramming, thus reusing existing ASP systems to capture various forms of qualitative preferences among answer sets. In this way, complex preferences and optimization capacities become readily available for ASP applications.
We address the problem of Finite Model Computation (FMC) of first-order theories and show that FMC can efficiently and transparently be solved by taking advantage of a recent extension of Answer Set Programming (ASP), called incremental Answer Set Programming (iASP). The idea is to use the incremental parameter in iASP programs to account for the domain size of a model. The FMC problem is then successively addressed for increasing domain sizes until an answer set, representing a finite model of the original first-order theory, is found. We implemented a system based on the iASP solver iClingo and demonstrate its competitiveness by showing that it slightly outperforms the winner of the FNT division of CADE's 2009 Automated Theorem Proving (ATP) competition on the respective benchmark collection.