Parametric LTL on Markov Chains

This paper is concerned with the verification of finite Markov chains against parametrized LTL (pLTL) formulas. In pLTL, the until-modality is equipped with a bound that contains variables; e.g., $\Diamond_{\le x}\ \varphi$ asserts that $\varphi$ holds within $x$ time steps, where $x$ is a variable on natural numbers. The central problem studied in this paper is to determine the set of parameter valuations $V_{\prec p} (\varphi)$ for which the probability to satisfy pLTL-formula $\varphi$ in a Markov chain meets a given threshold $\prec p$, where $\prec$ is a comparison on reals and $p$ a probability. As for pLTL determining the emptiness of $V_{> 0}(\varphi)$ is undecidable, we consider several logic fragments. We consider parametric reachability properties, a sub-logic of pLTL restricted to next and $\Diamond_{\le x}$, parametric B\"uchi properties and finally, a maximal subclass of pLTL for which emptiness of $V_{> 0}(\varphi)$ is decidable.Comment: TCS Track B 201

The signature of 44Ti in Cassiopeia A revealed by IBIS/ISGRI on INTEGRAL

We report the detection of both the 67.9 and 78.4 keV 44Sc gamma-ray lines in Cassiopeia A with the INTEGRAL IBIS/ISGRI instrument. Besides the robustness provided by spectro-imaging observations, the main improvements compared to previous measurements are a clear separation of the two 44Sc lines together with an improved significance of the detection of the hard X-ray continuum up to 100 keV. These allow us to refine the determination of the 44Ti yield and to constrain the nature of the nonthermal continuum emission. By combining COMPTEL, BeppoSAX/PDS and ISGRI measurements, we find a line flux of (2.5 +/- 0.3)*10(-5) cm(-2) s(-1) leading to a synthesized 44Ti mass of 1.6 (+0.6-0.3)*10(-4) solar mass. This high value suggests that Cas A is peculiar in comparison to other young supernova remnants, from which so far no line emission from 44Ti decay has been unambiguously detected.Comment: 5 pages, 4 figures, Accepted for publication in ApJ

Efficient Emptiness Check for Timed B\"uchi Automata (Extended version)

The B\"uchi non-emptiness problem for timed automata refers to deciding if a given automaton has an infinite non-Zeno run satisfying the B\"uchi accepting condition. The standard solution to this problem involves adding an auxiliary clock to take care of the non-Zenoness. In this paper, it is shown that this simple transformation may sometimes result in an exponential blowup. A construction avoiding this blowup is proposed. It is also shown that in many cases, non-Zenoness can be ascertained without extra construction. An on-the-fly algorithm for the non-emptiness problem, using non-Zenoness construction only when required, is proposed. Experiments carried out with a prototype implementation of the algorithm are reported.Comment: Published in the Special Issue on Computer Aided Verification - CAV 2010; Formal Methods in System Design, 201

Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections

Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use

MULTICUBE: Multi-objective design space exploration of multi-core architectures

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Is there a best Büchi automaton for explicit model checking?

LTL to Büchi automata (BA) translators are traditionally optimized to produce automata with a small number of states or a small number of non-deterministic states. In this paper, we search for properties of Büchi automata that really influence the performance of explicit model checkers. We do that by manual analysis of several automata and by experiments with common LTL-to-BA translators and realistic verification tasks. As a result of these experiences, we gain a better insight into the characteristics of automata that work well with Spin.Překladače LTL na Büchiho automaty jsou obvykle optimalizovány tak, aby produkovaly automaty s co nejmenším počtem stavů, či s co nejmenším počtem nedeterministických stavů. V této publikaci hledáme vlastnosti Büchiho automatů, které skutečně ovlivňují výkon nástrojů pro explicitní metodu ověřování modelu (model checking). A to pomocí manuální analýzy několika automatů a experimenty s běžnými překladače LTL na automaty a realistickými verifikačními úlohami. Výsledkem těchto experimentů je lepší porozumění charakteristik automatů, které jsou dobré pro model checker Spin

Metaphors in Nanomedicine: The Case of Targeted Drug Delivery

International audienceThe promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the 'therapeutic missile' commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich's 'magic bullet', has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the "therapeutic missile" is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An 'oïkological' approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general

Maternal Serologic Screening to Prevent Congenital Toxoplasmosis: A Decision-Analytic Economic Model

We constructed a decision-analytic and cost-minimization model to compare monthly maternal serological screening for congenital toxoplasmosis, prenatal treatment, and post-natal follow-up and treatment according to the current French protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. We use sensitivity analysis to evaluate robustness of results. We find that universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French (Paris) protocol, leads to savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, incidence of primary T. gondii infection during pregnancy, and to bivariate analysis of test costs and incidence of primary T. gondii infection. Given the parameters in this model and a maternal screening test cost of$12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities

A Set of 100 Chloroplast DNA Primer Pairs to Study Population Genetics and Phylogeny in Monocotyledons

Chloroplast DNA sequences are of great interest for population genetics and phylogenetic studies. However, only a small set of markers are commonly used. Most of them have been designed for amplification in a large range of Angiosperms and are located in the Large Single Copy (LSC). Here we developed a new set of 100 primer pairs optimized for amplification in Monocotyledons. Primer pairs amplify coding (exon) and non-coding regions (intron and intergenic spacer). They span the different chloroplast regions: 72 are located in the LSC, 13 in the Small Single Copy (SSC) and 15 in the Inverted Repeat region (IR). Amplification and sequencing were tested in 13 species of Monocotyledons: Dioscorea abyssinica, D. praehensilis, D. rotundata, D. dumetorum, D. bulbifera, Trichopus sempervirens (Dioscoreaceae), Phoenix canariensis, P. dactylifera, Astrocaryum scopatum, A. murumuru, Ceroxylon echinulatum (Arecaceae), Digitaria excilis and Pennisetum glaucum (Poaceae). The diversity found in Dioscorea, Digitaria and Pennisetum mainly corresponded to Single Nucleotide Polymorphism (SNP) while the diversity found in Arecaceae also comprises Variable Number Tandem Repeat (VNTR). We observed that the most variable loci (rps15-ycf1, rpl32-ccsA, ndhF-rpl32, ndhG-ndhI and ccsA) are located in the SSC. Through the analysis of the genetic structure of a wild-cultivated species complex in Dioscorea, we demonstrated that this new set of primers is of great interest for population genetics and we anticipate that it will also be useful for phylogeny and bar-coding studies

Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

Background - Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties. Results - Our results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years ¿ Myr) coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times. Conclusion - Molecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance, enhancing the levels of endemicity. These results provide an explanation for present day distribution patterns and origins of endemicity for African rain forest trees. Moreover, given the pre-Pleistocene origins of all the studied endemic East African genera and species, these results also offer important insights for setting conservation priorities in these highly diversified but threatene