Discrete-time rewards model-checked

This paper presents a model-checking approach for analyzing discrete-time Markov reward models. For this purpose, the temporal logic probabilistic CTL is extended with reward constraints. This allows to formulate complex measures – involving expected as well as accumulated rewards – in a precise and succinct way. Algorithms to efficiently analyze such formulae are introduced. The approach is illustrated by model-checking a probabilistic cost model of the IPv4 zeroconf protocol for distributed address assignment in ad-hoc networks

Immunisation with ‘naïve' syngeneic dendritic cells protects mice from tumour challenge

Dendritic cells (DCs) ‘pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50 000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-γ and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials

A Hierarchy of Scheduler Classes for Stochastic Automata

Stochastic automata are a formal compositional model for concurrent stochastic timed systems, with general distributions and non-deterministic choices. Measures of interest are defined over schedulers that resolve the nondeterminism. In this paper we investigate the power of various theoretically and practically motivated classes of schedulers, considering the classic complete-information view and a restriction to non-prophetic schedulers. We prove a hierarchy of scheduler classes w.r.t. unbounded probabilistic reachability. We find that, unlike Markovian formalisms, stochastic automata distinguish most classes even in this basic setting. Verification and strategy synthesis methods thus face a tradeoff between powerful and efficient classes. Using lightweight scheduler sampling, we explore this tradeoff and demonstrate the concept of a useful approximative verification technique for stochastic automata

Explicit Model Checking of Very Large MDP using Partitioning and Secondary Storage

The applicability of model checking is hindered by the state space explosion problem in combination with limited amounts of main memory. To extend its reach, the large available capacities of secondary storage such as hard disks can be exploited. Due to the specific performance characteristics of secondary storage technologies, specialised algorithms are required. In this paper, we present a technique to use secondary storage for probabilistic model checking of Markov decision processes. It combines state space exploration based on partitioning with a block-iterative variant of value iteration over the same partitions for the analysis of probabilistic reachability and expected-reward properties. A sparse matrix-like representation is used to store partitions on secondary storage in a compact format. All file accesses are sequential, and compression can be used without affecting runtime. The technique has been implemented within the Modest Toolset. We evaluate its performance on several benchmark models of up to 3.5 billion states. In the analysis of time-bounded properties on real-time models, our method neutralises the state space explosion induced by the time bound in its entirety.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-24953-7_1

Talking quiescence: a rigorous theory that supports parallel composition, action hiding and determinisation

The notion of quiescence - the absence of outputs - is vital in both behavioural modelling and testing theory. Although the need for quiescence was already recognised in the 90s, it has only been treated as a second-class citizen thus far. This paper moves quiescence into the foreground and introduces the notion of quiescent transition systems (QTSs): an extension of regular input-output transition systems (IOTSs) in which quiescence is represented explicitly, via quiescent transitions. Four carefully crafted rules on the use of quiescent transitions ensure that our QTSs naturally capture quiescent behaviour. We present the building blocks for a comprehensive theory on QTSs supporting parallel composition, action hiding and determinisation. In particular, we prove that these operations preserve all the aforementioned rules. Additionally, we provide a way to transform existing IOTSs into QTSs, allowing even IOTSs as input that already contain some quiescent transitions. As an important application, we show how our QTS framework simplifies the fundamental model-based testing theory formalised around ioco.Comment: In Proceedings MBT 2012, arXiv:1202.582

The quantitative verification benchmark set

We present an extensive collection of quantitative models to facilitate the development, comparison, and benchmarking of new verification algorithms and tools. All models have a formal semantics in terms of extensions of Markov chains, are provided in the Jani format, and are documented by a comprehensive set of metadata. The collection is highly diverse: it includes established probabilistic verification and planning benchmarks, industrial case studies, models of biological systems, dynamic fault trees, and Petri net examples, all originally specified in a variety of modelling languages. It archives detailed tool performance data for each model, enabling immediate comparisons between tools and among tool versions over time. The collection is easy to access via a client-side web application at qcomp.org with powerful search and visualisation features. It can be extended via a Git-based submission process, and is openly accessible according to the terms of the CC-BY license

From Eat to trEat : engineering the mitochondrial Eat1 enzyme for enhanced ethyl acetate production in Escherichia coli

Genetic engineering of microorganisms has become a common practice to establish microbial cell factories for a wide range of compounds. Ethyl acetate is an industrial solvent that is used in several applications, mainly as a biodegradable organic solvent with low toxicity. While ethyl acetate is produced by several natural yeast species, the main mechanism of production has remained elusive until the discovery of Eat1 in Wickerhamomyces anomalus. Unlike other yeast alcohol acetyl transferases (AATs), Eat1 is located in the yeast mitochondria, suggesting that the coding sequence contains a mitochondrial pre-sequence. For expression in prokaryotic hosts such as E. coli, expression of heterologous proteins with eukaryotic signal sequences may not be optimal. Results Unprocessed and synthetically truncated eat1 variants of Kluyveromyces marxianus and Wickerhamomyces anomalus have been compared in vitro regarding enzyme activity and stability. While the specific activity remained unaffected, half-life improved for several truncated variants. The same variants showed better performance regarding ethyl acetate production when expressed in E. coli. Conclusion By analysing and predicting the N-terminal pre-sequences of different Eat1 proteins and systematically trimming them, the stability of the enzymes in vitro could be improved, leading to an overall improvement of in vivo ethyl acetate production in E. coli. Truncated variants of eat1 could therefore benefit future engineering approaches towards efficient ethyl acetate production.publishedVersio