Ordered Navigation on Multi-attributed Data Words

We study temporal logics and automata on multi-attributed data words. Recently, BD-LTL was introduced as a temporal logic on data words extending LTL by navigation along positions of single data values. As allowing for navigation wrt. tuples of data values renders the logic undecidable, we introduce ND-LTL, an extension of BD-LTL by a restricted form of tuple-navigation. While complete ND-LTL is still undecidable, the two natural fragments allowing for either future or past navigation along data values are shown to be Ackermann-hard, yet decidability is obtained by reduction to nested multi-counter systems. To this end, we introduce and study nested variants of data automata as an intermediate model simplifying the constructions. To complement these results we show that imposing the same restrictions on BD-LTL yields two 2ExpSpace-complete fragments while satisfiability for the full logic is known to be as hard as reachability in Petri nets

Ehrenfeucht-Fraïssé goes elementarily automatic for structures of bounded degree

International audienceMany relational structures are automatically presentable, i.e. elements of the domain can be seen as words over a finite alphabet and equality and other atomic relations are represented with finite automata. The first-order theories over such structures are known to be primitive recursive, which is shown by the inductive construction of an automaton representing any relation definable in the first-order logic. We propose a general method based on Ehrenfeucht-Fraïssé games to give upper bounds on the size of these automata and on the time required to build them. We apply this method for two different automatic structures which have elementary decision procedures, Presburger Arithmetic and automatic structures of bounded degree. For the latter no upper bound on the size of the automata was known. We conclude that the very general and simple automata-based algorithm works well to decide the first-order theories over these structures

Abstract Regular Tree Model Checking

International audienceRegular (tree) model checking (RMC) is a promising generic method for formal verification of infinite-state systems. It encodes configurations of systems as words or trees over a suitable alphabet, possibly infinite sets of configurations as finite word or tree automata, and operations of the systems being examined as finite word or tree transducers. The reachability set is then computed by a repeated application of the transducers on the automata representing the currently known set of reachable configurations. In order to facilitate termination of RMC, various acceleration schemas have been proposed. One of them is a combination of RMC with the abstract-check-refine paradigm yielding the so-called abstract regular model checking (ARMC). ARMC has originally been proposed for word automata and transducers only and thus for dealing with systems with linear (or easily linearisable) structure. In this paper, we propose a generalisation of ARMC to the case of dealing with trees which arise naturally in a lot of modelling and verification contexts. In particular, we first propose abstractions of tree automata based on collapsing their states having an equal language of trees up to some bounded height. Then, we propose an abstraction based on collapsing states having a non-empty intersection (and thus "satisfying") the same bottom-up tree "predicate" languages. Finally, we show on several examples that the methods we propose give us very encouraging verification results

A Robust Class of Data Languages and an Application to Learning

We introduce session automata, an automata model to process data words, i.e., words over an infinite alphabet. Session automata support the notion of fresh data values, which are well suited for modeling protocols in which sessions using fresh values are of major interest, like in security protocols or ad-hoc networks. Session automata have an expressiveness partly extending, partly reducing that of classical register automata. We show that, unlike register automata and their various extensions, session automata are robust: They (i) are closed under intersection, union, and (resource-sensitive) complementation, (ii) admit a symbolic regular representation, (iii) have a decidable inclusion problem (unlike register automata), and (iv) enjoy logical characterizations. Using these results, we establish a learning algorithm to infer session automata through membership and equivalence queries

Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer

<p>Abstract</p> <p>Introduction</p> <p>To evaluate efficacy and secondary resectability in patients with locally advanced pancreatic cancer (LAPC) treated with neoadjuvant chemoradiotherapy (CRT).</p> <p>Patients and methods</p> <p>A total of 215 patients with locally advanced pancreatic cancer were treated with chemoradiation at a single institution. Radiotherapy was delivered with a median dose of 52.2 Gy in single fractions of 1.8 Gy. Chemotherapy was applied concomitantly as gemcitabine (GEM) at a dose of 300 mg/m²weekly, followed by adjuvant cycles of full-dose GEM (1000 mg/m²). After neoadjuvant CRT restaging was done to evaluate secondary resectability. Overall and disease-free survival were calculated and prognostic factors were estimated.</p> <p>Results</p> <p>After CRT a total of 26% of all patients with primary unresectable LAPC were chosen to undergo secondary resection. Tumour free resection margins could be achieved in 39.2% (R0-resection), R1-resections were seen in 41.2%, residual macroscopic tumour in 11.8% (R2) and in 7.8% resection were classified as Rx. Patients with complete resection after CRT showed a significantly increased median overall survival (OS) with 22.1 compared to 11.9 months in non-resected patients. Median OS and disease-free survival (DFS) of all patients were 12.3 and 8.1 months respectively. In most cases the first site of disease progression was systemic with hepatic (52%) and peritoneal (36%) metastases.</p> <p>Discussion</p> <p>A high percentage of patients with locally advanced pancreatic cancer can undergo secondary resection after gemcitabine-based chemoradiation and has a relative long-term prognosis after complete resection.</p

Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway

BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. METHODS: Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-x(L )and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine

Sur la vérification de systèmes infinis

This thesis is about the verification problem of systems having an infinite number of states. These systems can be described by several formalisms like process algebras or automata together with unbounded data-structures (push-down automata, Petri nets or communicating finite-state machines). In a first part of the thesis we study the characterization of classes of infinite-state systems and properties for which the verification problem is decidable. First, we consider the complexity of the verification problem of the linear-time mu-calculus for Petri nets. Then, we define temporal logics which allow to express non-regular properties containing linear constraints on the number of occurrences of events. These logics are more expressive than known logics in this domain. We show in particular that the verification problem of a logic which is more expressive than the linear-time mu-calculus is decidable for classes of systems like push-down automata and Petri nets. A second part of the thesis is dedicated to communicating finite-state machines. Their verification problem is in general undecidable. We apply the symbolic analysis principle to these systems. We propose finite structures which allow to represent and manipulate infinite sets of configurations of these systems. These structures allow to calculate the exact effect of a repeated execution of every circuit in the transition graph of the system. Thus, every circuit of the transition graph of the system can be considered as a new "transition" of the system. We use this result to accelerate the computation of the set of reachable states of a system in order to increase the chance of termination.Cette thèse traite du problème de la vérification de systèmes ayant un nombre infini d'états. Ces systèmes peuvent être décrits par plusieurs formalismes tels que des algèbres de processus ou des automates finis munis de structures de données non-bornées (automates à pile, réseaux de Petri ou systèmes à files). Dans une première partie de la thèse nous nous intéressons à la caractérisation de classes de systèmes infinis et de propriétés pour lesquels le problème de vérification est décidable. Nous considérons d'abord la complexité de la vérification du mu-calcul linéaire pour les réseaux de Petri. Ensuite, nous définissons des logiques temporelles qui permettent d'exprimer des propriétés non-régulières comportant des contraintes linéaires sur le nombre d'occurrences d'événements. Ces logiques sont plus expressives que les logiques utilisées dans le domaine. Nous montrons en particulier que le problème de la vérification d'une logique qui est plus expressive que le mu-calcul linéaire est décidable pour des classes de systèmes infinis telles que les automates à pile et les réseaux de Petri. Une deuxième partie de la thèse est consacrée aux systèmes communicant par files d'attente, dont le problème de vérification est en général indécidable. Nous appliquons le principe de l'analyse symbolique à ces systèmes. Nous proposons des structures finies qui permettent de représenter et de manipuler des ensembles infinis de configurations de tels systèmes. Ces structures permettent de calculer l'effet exact d'une exécution répétée de tout circuit dans le graphe de transitions du système. Ainsi, chaque circuit peut être considéré comme une nouvelle "transition" du système. Nous utilisons ce résultat pour accélérer le calcul de l'ensemble des configurations atteignables d'un système afin d'augmenter les chances de terminaison de ce calcul