Automated Analysis of Industrial Workflow-based Models

International audienceModelling and governance of business processes are important concerns in companies all over the world. By better understanding business processes, different optimizations are made possible, concretely resulting into potential efficiency gains, cost reductions and improvements in agility. The use of formal specification languages for the modelling of business processes paves the way for different kinds of automated analysis. Such analysis can be used to infer properties from the modelled processes that can be used to improve their design. In this paper, we particularly explore two important classes of verification, namely verification of behavioural properties using model checking techniques and data-based analysis using SAT solving. Those verifications are fully automated by using different tools such as the CADP verification toolbox and the Z3 solver. We illustrate our approach on a real-world case study

Is There Such a Thing as Psychological Pain? and Why It Matters

Medicine regards pain as a signal of physical injury to the body despite evidence contradicting the linkage and despite the exclusion of vast numbers of sufferers who experience psychological pain. By broadening our concept of pain and making it more inclusive, we would not only better accommodate the basic science of pain but also would recognize what is already appreciated by the layperson—that pain from diverse sources, physical and psychological, share an underlying felt structure

Toward Evidence-Based Genetic Research on Lifelong Premature Ejaculation: A Critical Evaluation of Methodology

Recently, four premature ejaculation (PE) subtypes have been distinguished on the basis of the duration of the intravaginal ejaculation latency time (IELT). These four PE subtypes have different etiologies and pathogeneses. Genetic research on PE should consider the existence of these PE subtypes and the accurate measurement of the IELT with a stopwatch. Currently, three methods of genetic research on PE have been used. They differ in the investigated population, tool of measurement, study design, and variables of PE. From animal and human research, it is derived that the central serotonergic system "modulates" ejaculation, whereas the ejaculation (reflex) itself is probably not under direct influence of the serotonergic system, but rather under the influence of other neurotransmitter systems in the spinal cord. For genetic research on PE, it is important to take into account that the (serotonergic) modulation of the IELT is variable among men and may even be absent. This means that serotonergic genetic polymorphisms may only be found in men with PE who respond with an ejaculation delay treatment with a selective serotonin reuptake inhibitor

Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure

Cells are exposed to oxidative stress and reactive metabolites every day. The Nrf2 signaling pathway responds to oxidative stress by upregulation of antioxidants like glutathione (GSH) to compensate the stress insult and re-establish homeostasis. Although mechanisms describing the interaction between the key pathway constituents Nrf2, Keap1 and p62 are widely reviewed and discussed in literature, quantitative dynamic models bringing together these mechanisms with time-resolved data are limited. Here, we present an ordinary differential equation (ODE) based dynamic model to describe the dynamic response of Nrf2, Keap1, Srxn1 and GSH to oxidative stress caused by the soft-electrophile diethyl maleate (DEM). The time-resolved data obtained by single-cell confocal microscopy of green fluorescent protein (GFP) reporters and qPCR of the Nrf2 pathway components complemented with siRNA knock down experiments, is accurately described by the calibrated mathematical model. We show that the quantitative model can describe the activation of the Nrf2 pathway by compounds with a different mechanism of activation, including drugs which are known for their ability to cause drug induced liver-injury (DILI) i.e., diclofenac (DCF) and omeprazole (OMZ). Finally, we show that our model can reveal differences in the processes leading to altered activation dynamics amongst DILI inducing drugs.Toxicolog