Reliability analysis of dynamic systems by translating temporal fault trees into Bayesian networks

Classical combinatorial fault trees can be used to assess combinations of failures but are unable to capture sequences of faults, which are important in complex dynamic systems. A number of proposed techniques extend fault tree analysis for dynamic systems. One of such technique, Pandora, introduces temporal gates to capture the sequencing of events and allows qualitative analysis of temporal fault trees. Pandora can be easily integrated in model-based design and analysis techniques. It is, therefore, useful to explore the possible avenues for quantitative analysis of Pandora temporal fault trees, and we identify Bayesian Networks as a possible framework for such analysis. We describe how Pandora fault trees can be translated to Bayesian Networks for dynamic dependability analysis and demonstrate the process on a simplified fuel system model. The conversion facilitates predictive reliability analysis of Pandora fault trees, but also opens the way for post-hoc diagnostic analysis of failures

Quantifying the contribution of transcription factor activity, mutations and microRNAs to CD274 expression in cancer patients

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis have been remarkably successful in inducing tumor remissions in several human cancers, yet a substantial number of patients do not respond to treatment. Because this may be partially due to the mechanisms giving rise to high PD-L1 expression within a patient, it is highly relevant to fully understand these mechanisms. In this study, we conduct a bioinformatic analysis to quantify the relative importance of transcription factor (TF) activity, microRNAs (miRNAs) and mutations in determining PD-L1 (CD274) expression at mRNA level based on data from the Cancer Genome Atlas. To predict individual CD274 levels based on TF activity, we developed multiple linear regression models by taking the expression of target genes of the TFs known to directly target PD-L1 as independent variables. This analysis showed that IRF1, STAT1, NFKB and BRD4 are the most important regulators of CD274 expression, explaining its mRNA levels in 90-98% of the patients. Because the remaining patients had high CD274 levels independent of these TFs, we next investigated whether mutations associated with increased CD274 mRNA levels, and low levels of miRNAs associated with negative regulation of CD274 expression could cause high CD274 levels in these patients. We found that mutations or miRNAs offered an explanation for high CD274 levels in 81-100% of the underpredicted patients. Thus, CD274 expression is largely explained by TF activity, and the remaining unexplained cases can largely be explained by mutations or low miRNA abundance.Toxicolog

Quantification of temporal fault trees based on fuzzy set theory

© Springer International Publishing Switzerland 2014. Fault tree analysis (FTA) has been modified in different ways to make it capable of performing quantitative and qualitative safety analysis with temporal gates, thereby overcoming its limitation in capturing sequential failure behaviour. However, for many systems, it is often very difficult to have exact failure rates of components due to increased complexity of systems, scarcity of necessary statistical data etc. To overcome this problem, this paper presents a methodology based on fuzzy set theory to quantify temporal fault trees. This makes the imprecision in available failure data more explicit and helps to obtain a range of most probable values for the top event probability

Hennessy-Milner Logic with Greatest Fixed Points as a Complete Behavioural Specification Theory

There are two fundamentally different approaches to specifying and verifying properties of systems. The logical approach makes use of specifications given as formulae of temporal or modal logics and relies on efficient model checking algorithms; the behavioural approach exploits various equivalence or refinement checking methods, provided the specifications are given in the same formalism as implementations. In this paper we provide translations between the logical formalism of Hennessy-Milner logic with greatest fixed points and the behavioural formalism of disjunctive modal transition systems. We also introduce a new operation of quotient for the above equivalent formalisms, which is adjoint to structural composition and allows synthesis of missing specifications from partial implementations. This is a substantial generalisation of the quotient for deterministic modal transition systems defined in earlier papers

Synaptotagmin interaction with SNAP-25 governs vesicle docking, priming, and fusion triggering

SNARE complex assembly constitutes a key step in exocytosis that is rendered C