Towards a Notion of Distributed Time for Petri Nets

We set the ground for research on a timed extension of Petri nets where time parameters are associated with tokens and arcs carry constraints that qualify the age of tokens required for enabling. The novelty is that, rather than a single global clock, we use a set of unrelated clocks --- possibly one per place --- allowing a local timing as well as distributed time synchronisation. We give a formal definition of the model and investigate properties of local versus global timing, including decidability issues and notions of processes of the respective models

Limit Synchronization in Markov Decision Processes

Markov decision processes (MDP) are finite-state systems with both strategic and probabilistic choices. After fixing a strategy, an MDP produces a sequence of probability distributions over states. The sequence is eventually synchronizing if the probability mass accumulates in a single state, possibly in the limit. Precisely, for 0 <= p <= 1 the sequence is p-synchronizing if a probability distribution in the sequence assigns probability at least p to some state, and we distinguish three synchronization modes: (i) sure winning if there exists a strategy that produces a 1-synchronizing sequence; (ii) almost-sure winning if there exists a strategy that produces a sequence that is, for all epsilon > 0, a (1-epsilon)-synchronizing sequence; (iii) limit-sure winning if for all epsilon > 0, there exists a strategy that produces a (1-epsilon)-synchronizing sequence. We consider the problem of deciding whether an MDP is sure, almost-sure, limit-sure winning, and we establish the decidability and optimal complexity for all modes, as well as the memory requirements for winning strategies. Our main contributions are as follows: (a) for each winning modes we present characterizations that give a PSPACE complexity for the decision problems, and we establish matching PSPACE lower bounds; (b) we show that for sure winning strategies, exponential memory is sufficient and may be necessary, and that in general infinite memory is necessary for almost-sure winning, and unbounded memory is necessary for limit-sure winning; (c) along with our results, we establish new complexity results for alternating finite automata over a one-letter alphabet

Reachability in Higher-Order-Counters

Higher-order counter automata (\HOCS) can be either seen as a restriction of higher-order pushdown automata (\HOPS) to a unary stack alphabet, or as an extension of counter automata to higher levels. We distinguish two principal kinds of \HOCS: those that can test whether the topmost counter value is zero and those which cannot. We show that control-state reachability for level $k$ \HOCS with $0$-test is complete for \mbox{$(k-2)$}-fold exponential space; leaving out the $0$-test leads to completeness for \mbox{$(k-2)$}-fold exponential time. Restricting \HOCS (without $0$-test) to level $2$, we prove that global (forward or backward) reachability analysis is \PTIME-complete. This enhances the known result for pushdown systems which are subsumed by level $2$ \HOCS without $0$-test. We transfer our results to the formal language setting. Assuming that \PTIME \subsetneq \PSPACE \subsetneq \mathbf{EXPTIME}, we apply proof ideas of Engelfriet and conclude that the hierarchies of languages of \HOPS and of \HOCS form strictly interleaving hierarchies. Interestingly, Engelfriet's constructions also allow to conclude immediately that the hierarchy of collapsible pushdown languages is strict level-by-level due to the existing complexity results for reachability on collapsible pushdown graphs. This answers an open question independently asked by Parys and by Kobayashi.Comment: Version with Full Proofs of a paper that appears at MFCS 201

Current issues in research on structure–property relationships in polymer nanocomposites

The understanding of the basic physical relationships between nano-scale structural variables and the macroscale properties of polymer nanocomposites remains in its infancy. The primary objective of this article is to ascertain the state of the art regarding the understanding and prediction of the macroscale properties of polymers reinforced with nanometer-sized solid inclusions over a wide temperature range. We emphasize that the addition of nanoparticles with large specific surface area to polymer matrices leads to amplification of a number of rather distinct molecular processes resulting from interactions between chains and solid surfaces. This results in a “non-classical” response of these systems to mechanical and electro-optical excitations when measured on the macroscale. For example, nanoparticles are expected to be particularly effective at modifying the intrinsic nano-scale dynamic heterogeneity of polymeric glass-formation and, correspondingly, recent simulations indicate that both the strength of particle interaction with the polymer matrix and the particle concentration can substantially influence the dynamic fragility of polymer glass-formation, a measure of the strength of the temperature dependence of the viscosity or structural relaxation time. Another basic characteristic of nanoparticles in polymer matrices is the tendency for the particles to associate into extended structures that can dominate the rheological, viscoelastic and mechanical properties of the nanocomposite so that thermodynamic factors that effect nanoparticle dispersion can be crucially important. Opportunities to exploit knowledge gained from understanding biomechanics of hierarchical biological protein materials and potential applications in materials design and nanotechnology are among future research challenges. Research on nanocomposites formed from block copolymers and nanoparticles offers huge promise in molecular electronics and photovoltaics. The surface functionalization of nanoparticles by the grafting of polymer brushes is expected to play important role in the designing of novel organic/inorganic nanocomposite materials. The formation of bulk heterojunctions at the nanometer scale leads to efficient dissociation of the charge pairs generated under sunlight. Based on the presentations and discussion, we make recommendations for future work in this area by the physics, chemistry, and engineering communities.Czech Republic. Ministry of Education, Youth, and Sports (MSM0021630501

Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

<p>Abstract</p> <p>Background</p> <p>Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation.</p> <p>Methods</p> <p>Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge.</p> <p>Results</p> <p>Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration.</p> <p>Conclusion</p> <p>Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.</p

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

<p>Abstract</p> <p>Background</p> <p>Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.</p> <p>Methods</p> <p>Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry.</p> <p>Results</p> <p>Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by <it>in vivo </it>pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown <it>in vitro</it>. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R.</p> <p>Conclusions</p> <p>We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.</p