Asynchronous Games over Tree Architectures

We consider the task of controlling in a distributed way a Zielonka asynchronous automaton. Every process of a controller has access to its causal past to determine the next set of actions it proposes to play. An action can be played only if every process controlling this action proposes to play it. We consider reachability objectives: every process should reach its set of final states. We show that this control problem is decidable for tree architectures, where every process can communicate with its parent, its children, and with the environment. The complexity of our algorithm is l-fold exponential with l being the height of the tree representing the architecture. We show that this is unavoidable by showing that even for three processes the problem is EXPTIME-complete, and that it is non-elementary in general

Local Strategy Improvement for Parity Game Solving

The problem of solving a parity game is at the core of many problems in model checking, satisfiability checking and program synthesis. Some of the best algorithms for solving parity game are strategy improvement algorithms. These are global in nature since they require the entire parity game to be present at the beginning. This is a distinct disadvantage because in many applications one only needs to know which winning region a particular node belongs to, and a witnessing winning strategy may cover only a fractional part of the entire game graph. We present a local strategy improvement algorithm which explores the game graph on-the-fly whilst performing the improvement steps. We also compare it empirically with existing global strategy improvement algorithms and the currently only other local algorithm for solving parity games. It turns out that local strategy improvement can outperform these others by several orders of magnitude

Structural abnormalities of the optic nerve and retina in Huntington’s disease pre-clinical and clinical settings

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies

Experimental calibration for DCDC specimens

The main advantages of DCDC-specimens are their completely stable crack extension properties and very high path stability due to the strongly negative T-stress term. Unfortunately, problems of DCDC tests can be identified by comparing experimental results that show for different materials (silicon nitride, glass) deviations from the results to be expected by 2-dimensional FE modelling as usual done in literature. Experimental calibrations on silicon nitrides and mixtures of silicon nitride and silicon carbide resulted in modified relations deviating from FE-results in literature. As a possible source for the differences of measurements and 2-D-FE results, we identified the influence of Poisson’s number. This parameter obviously causes deviations between straight-crack assumption in FEmodelling and observable curved crack fronts in the experiments. In order to avoid specimen buckling we also used short specimens of roughly half length. This may slightly affect the stress intensity factors

Angiogenic Activity of Sera from Pulmonary Tuberculosis Patients in Relation to IL-12p40 and TNFα Serum Levels

The role of angiogenesis in the pathogenesis of tuberculosis (TB) is not clear. The aim of this study was to examine the effect of sera from TB patients on angiogenesis induced by different subsets of normal human mononuclear cells (MNC) in relation to IL-12p40 and TNFα serum levels. Serum samples from 36 pulmonary TB patients and from 22 healthy volunteers were evaluated. To assess angiogenic reaction the leukocytes-induced angiogenesis test according to Sidky and Auerbach was performed. IL-12p40 and TNFα serum levels were evaluated by ELISA. Sera from TB patients significantly stimulated angiogenic activity of MNC compared to sera from healthy donors and PBS (p < 0.001). The number of microvessels formed after injection of lymphocytes preincubated with sera from TB patients was significantly lower compared to the number of microvessels created after injection of MNC preincubated with the same sera (p < 0.016). However, the number of microvessels created after the injection of lymphocytes preincubated with sera from healthy donors or with PBS alone was significantly higher (p < 0.017). The mean levels of IL-12p40 and TNFα were significantly elevated in sera from TB patients compared to healthy donors. We observed a correlation between angiogenic activity of sera from TB patients and IL-12p40 and TNFα serum levels (p < 0.01). Sera from TB patients constitute a source of mediators that participate in angiogenesis and prime monocytes for production of proangiogenic factors. The main proangiogenic effect of TB patients’ sera is mediated by macrophages/monocytes. TNFα and IL-12p40 may indirectly stimulate angiogenesis in TB

Measuring Permissiveness in Parity Games: Mean-Payoff Parity Games Revisited

We study nondeterministic strategies in parity games with the aim of computing a most permissive winning strategy. Following earlier work, we measure permissiveness in terms of the average number/weight of transitions blocked by the strategy. Using a translation into mean-payoff parity games, we prove that the problem of computing (the permissiveness of) a most permissive winning strategy is in NP intersected coNP. Along the way, we provide a new study of mean-payoff parity games. In particular, we prove that the opponent player has a memoryless optimal strategy and give a new algorithm for solving these games.Comment: 30 pages, revised versio

The γ-secretase substrate proteome and its role in cell signaling regulation

γ-Secretases mediate the regulated intramembrane proteolysis (RIP) of more than 150 integral membrane proteins. We developed an unbiased γ-secretase substrate identification (G-SECSI) method to study to what extent these proteins are processed in parallel. We demonstrate here parallel processing of at least 85 membrane proteins in human microglia in steady-state cell culture conditions. Pharmacological inhibition of γ-secretase caused substantial changes of human microglial transcriptomes, including the expression of genes related to the disease-associated microglia (DAM) response described in Alzheimer disease (AD). While the overall effects of γ-secretase deficiency on transcriptomic cell states remained limited in control conditions, exposure of mouse microglia to AD-inducing amyloid plaques strongly blocked their capacity to mount this putatively protective DAM cell state. We conclude that γ-secretase serves as a critical signaling hub integrating the effects of multiple extracellular stimuli into the overall transcriptome of the cell

Analysis of Communicating Automata

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