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

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

Electric-field-induced alignment of electrically neutral disk-like particles: modelling and calculation

This work reveals a torque from electric field to electrically neutral flakes that are suspended in a higher electrical conductive matrix. The torque tends to rotate the particles toward an orientation with its long axis parallel to the electric current flow. The alignment enables the anisotropic properties of tiny particles to integrate together and generate desirable macroscale anisotropic properties. The torque was obtained from thermodynamic calculation of electric current free energy at various microstructure configurations. It is significant even when the electrical potential gradient becomes as low as 100 v/m. The changes of electrical, electroplastic and thermal properties during particles alignment were discussed

Symbolic Verification and Strategy Synthesis for Linearly-Priced Probabilistic Timed Automata

Probabilistic timed automata are a formalism for modelling systems whose dynamics includes probabilistic, nondeterministic and timed aspects including real-time systems. A variety of techniques have been proposed for the analysis of this formalism and successfully employed to analyse, for example, wireless communication protocols and computer security systems. Augmenting the model with prices (or, equivalently, costs or rewards) provides a means to verify more complex quantitative properties, such as the expected energy usage of a device or the expected number of messages sent during a protocol’s execution. However, the analysis of these properties on probabilistic timed automata currently relies on a technique based on integer discretisation of real-valued clocks, which can be expensive in some cases. In this paper, we propose symbolic techniques for verification and optimal strategy synthesis for priced probabilistic timed automata which avoid this discretisation. We build upon recent work for the special case of expected time properties, using value iteration over a zone-based abstraction of the model

Using electric current to surpass the microstructure breakup limit

The elongated droplets and grains can break up into smaller ones. This process is driven by the interfacial free energy minimization, which gives rise to a breakup limit. We demonstrated in this work that the breakup limit can be overpassed drastically by using electric current to interfere. Electric current free energy is dependent on the microstructure configuration. The breakup causes the electric current free energy to reduce in some cases. This compensates the increment of interfacial free energy during breaking up and enables the processing to achieve finer microstructure. With engineering practical electric current parameters, our calculation revealed a significant increment of the obtainable number of particles, showing electric current a powerful microstructure refinement technology. The calculation is validated by our experiments on the breakup of Fe3C-plates in Fe matrix. Furthermore, there is a parameter range that electric current can drive spherical particles to split into smaller ones

Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8(+ )T cells by dendritic cells loaded with killed allogeneic breast cancer cells

INTRODUCTION: The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity. METHODS: In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8(+ )T cells in 2-week and/or 3-week cultures. CD8(+ )T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-γ) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens. RESULTS: We found that DCs loaded with killed breast cancer cells can prime naïve CD8(+ )T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201(- )breast cancer cells can kill HLA-A*0201(+ )breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin. CONCLUSION: This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer

Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection