Extending Hybrid CSP with Probability and Stochasticity

Probabilistic and stochastic behavior are omnipresent in computer controlled systems, in particular, so-called safety-critical hybrid systems, because of fundamental properties of nature, uncertain environments, or simplifications to overcome complexity. Tightly intertwining discrete, continuous and stochastic dynamics complicates modelling, analysis and verification of stochastic hybrid systems (SHSs). In the literature, this issue has been extensively investigated, but unfortunately it still remains challenging as no promising general solutions are available yet. In this paper, we give our effort by proposing a general compositional approach for modelling and verification of SHSs. First, we extend Hybrid CSP (HCSP), a very expressive and process algebra-like formal modeling language for hybrid systems, by introducing probability and stochasticity to model SHSs, which is called stochastic HCSP (SHCSP). To this end, ordinary differential equations (ODEs) are generalized by stochastic differential equations (SDEs) and non-deterministic choice is replaced by probabilistic choice. Then, we extend Hybrid Hoare Logic (HHL) to specify and reason about SHCSP processes. We demonstrate our approach by an example from real-world.Comment: The conference version of this paper is accepted by SETTA 201

Social behavior shapes the chimpanzee pan-microbiome

Animal sociality facilitates the transmission of pathogenic microorganisms among hosts, but the extent to which sociality enables animals’ beneficial microbial associations is poorly understood. The question is critical because microbial communities, particularly those in the gut, are key regulators of host health. We show evidence that chimpanzee social interactions propagate microbial diversity in the gut microbiome both within and between host generations. Frequent social interaction promotes species richness within individual microbiomes as well as homogeneity among the gut community memberships of different chimpanzees. Sampling successive generations across multiple chimpanzee families suggests that infants inherited gut microorganisms primarily through social transmission. These results indicate that social behavior generates a pan-microbiome, preserving microbial diversity across evolutionary time scales and contributing to the evolution of host species–specific gut microbial communities

Mean-Payoff Optimization in Continuous-Time Markov Chains with Parametric Alarms

Continuous-time Markov chains with alarms (ACTMCs) allow for alarm events that can be non-exponentially distributed. Within parametric ACTMCs, the parameters of alarm-event distributions are not given explicitly and can be subject of parameter synthesis. An algorithm solving the $\varepsilon$-optimal parameter synthesis problem for parametric ACTMCs with long-run average optimization objectives is presented. Our approach is based on reduction of the problem to finding long-run average optimal strategies in semi-Markov decision processes (semi-MDPs) and sufficient discretization of parameter (i.e., action) space. Since the set of actions in the discretized semi-MDP can be very large, a straightforward approach based on explicit action-space construction fails to solve even simple instances of the problem. The presented algorithm uses an enhanced policy iteration on symbolic representations of the action space. The soundness of the algorithm is established for parametric ACTMCs with alarm-event distributions satisfying four mild assumptions that are shown to hold for uniform, Dirac and Weibull distributions in particular, but are satisfied for many other distributions as well. An experimental implementation shows that the symbolic technique substantially improves the efficiency of the synthesis algorithm and allows to solve instances of realistic size.Comment: This article is a full version of a paper accepted to the Conference on Quantitative Evaluation of SysTems (QEST) 201

The role of external broadcasting in a closed political system

This article investigates the role and impact of external broadcasting (radio and television) on a closed political system, through the example of the two post-war German states: the West German Federal Republic of Germany (FRG) and the East German German Democratic Republic (GDR). The aim is to debunk myths about the influence of external broadcasting on the events that led to German reunification in 1990. The study follows a historical approach and discusses what role external media played during the years of a divided Germany. The findings are based on several historical sources, research reports from the 1950s and 1960s and over 100 biographical interviews with former residents of the German Democratic Republic (GDR). The article analyses the impact of external broadcasting on citizens and the political elite in times of crisis as well as during everyday life

Optimizing Performance of Continuous-Time Stochastic Systems using Timeout Synthesis

We consider parametric version of fixed-delay continuous-time Markov chains (or equivalently deterministic and stochastic Petri nets, DSPN) where fixed-delay transitions are specified by parameters, rather than concrete values. Our goal is to synthesize values of these parameters that, for a given cost function, minimise expected total cost incurred before reaching a given set of target states. We show that under mild assumptions, optimal values of parameters can be effectively approximated using translation to a Markov decision process (MDP) whose actions correspond to discretized values of these parameters

Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity in Drosophila

G4C2 repeat expansions within the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeats undergo repeat-associated non-ATG translation to generate toxic dipeptide repeat proteins. Here, we show that insulin/Igf signalling is reduced in fly models of C9orf72 repeat expansion using RNA-sequencing of adult brain. We further demonstrate that activation of insulin/Igf signalling can mitigate multiple neurodegenerative phenotypes in flies expressing either expanded G4C2 repeats or the toxic dipeptide repeat protein poly-GR. Levels of poly-GR are reduced when components of the insulin/Igf signalling pathway are genetically activated in the diseased flies, suggesting a mechanism of rescue. Modulating insulin signalling in mammalian cells also lowers poly-GR levels. Remarkably, systemic injection of insulin improves the survival of flies expressing G4C2 repeats. Overall, our data suggest that modulation of insulin/Igf signalling could be an effective therapeutic approach against C9orf72 ALS/FTD

Biomarker Testing to Estimate Under-Reported Heavy Alcohol Consumption by Persons with HIV Initiating ART in Uganda

Alcohol affects the transmission and treatment of HIV, yet may be under-reported in resource-limited settings. We compared self-reported alcohol consumption with levels of plasma carbohydrate-deficient transferrin (%CDT), a biomarker of heavy alcohol consumption, in persons initiating antiretroviral therapy in Uganda. Almost seven percent (6.7%) of persons reporting abstaining and 10% reporting consuming 1–40 drinks in the prior month tested positive for %CDT, and actual under-report may be higher due to low sensitivity of %CDT. These results suggest likely under-report in those reporting abstaining and current drinking. Improved identification of heavy alcohol consumption is needed for research and clinical purposes

Next-to-leading order QCD corrections to Higgs boson production in association with a photon via weak-boson fusion at the LHC

Higgs boson production in association with a hard central photon and two forward tagging jets is expected to provide valuable information on Higgs boson couplings in a range where it is difficult to disentangle weak-boson fusion processes from large QCD backgrounds. We present next-to-leading order QCD corrections to Higgs production in association with a photon via weak-boson fusion at a hadron collider in the form of a flexible parton-level Monte Carlo program. The QCD corrections to integrated cross sections are found to be small for experimentally relevant selection cuts, while the shape of kinematic distributions can be distorted by up to 20% in some regions of phase space. Residual scale uncertainties at next-to-leading order are at the few-percent level.Comment: 17 pages, 7 figures, 1 tabl

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Feynman rules for the rational part of the Electroweak 1-loop amplitudes

We present the complete set of Feynman rules producing the rational terms of kind R_2 needed to perform any 1-loop calculation in the Electroweak Standard Model. Our results are given both in the 't Hooft-Veltman and in the Four Dimensional Helicity regularization schemes. We also verified, by using both the 't Hooft-Feynman gauge and the Background Field Method, a huge set of Ward identities -up to 4-points- for the complete rational part of the Electroweak amplitudes. This provides a stringent check of our results and, as a by-product, an explicit test of the gauge invariance of the Four Dimensional Helicity regularization scheme in the complete Standard Model at 1-loop. The formulae presented in this paper provide the last missing piece for completely automatizing, in the framework of the OPP method, the 1-loop calculations in the SU(3) X SU(2) X U(1) Standard Model.Comment: Many thanks to Huasheng Shao for having recomputed, independently of us, all of the ${\rm R_2}$ effective vertices. Thanks to his help and by comparing with an independent computation we performed in a general $R_\xi$ gauge, we could fix, in the present version, the following formulae: the vertex $A l \bar l$ in Eq. (3.6), the vertex $Z \phi^+ \phi^-$ in Eq. (3.8), Eqs (3.16), (3.17) and (3.18