A formal approach for correct-by-construction system substitution

Safety-critical systems depend on the fact that their software components provide services that behave correctly (i.e. satisfy their requirements). Additionally, in many cases, these systems have to be adapted or reconfigured in case of failures or when changes in requirements or in quality of service occur. When these changes appear at the software level, they can be handled by the notion of substitution. Indeed, the software component of the source system can be substituted by another software component to build a new target system. In the case of safety-critical systems, it is mandatory that this operation enforces that the new target system behaves correctly by preserving the safety properties of the source system during and after the substitution operation. In this thesis, the studied systems are modeled as state-transition systems. In order to model system substitution, the Event-B method has been selected as it is well suited to model such state-transition systems and it provides the benefits of refinement, proof and the availability of a strong tooling with the Rodin Platform. This thesis provides a generic model for system substitution that entails different situations like cold start and warm start as well as the possibility of system degradation, upgrade or equivalence substitutions. This proposal is first used to formalize substitution in the case of discrete systems applied to web services compensation and allowed modeling correct compensation. Then, it is also used for systems characterized by continuous behaviors like hybrid systems. To model continuous behaviors with Event-B, the Theory plug-in for Rodin is investigated and proved successful for modeling hybrid systems. Afterwards, a correct substitution mechanism for systems with continuous behaviors is proposed. A safety envelope for the output of the system is taken as the safety requirement. Finally, the proposed approach is generalized, enabling the derivation of the previously defined models for web services compensation through refinement, and the reuse of proofs across system models

On Synchronous and Asynchronous Monitor Instrumentation for Actor-based systems

We study the impact of synchronous and asynchronous monitoring instrumentation on runtime overheads in the context of a runtime verification framework for actor-based systems. We show that, in such a context, asynchronous monitoring incurs substantially lower overhead costs. We also show how, for certain properties that require synchronous monitoring, a hybrid approach can be used that ensures timely violation detections for the important events while, at the same time, incurring lower overhead costs that are closer to those of an asynchronous instrumentation.Comment: In Proceedings FOCLASA 2014, arXiv:1502.0315

Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue.

The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation

GUBS, a Behavior-based Language for Open System Dedicated to Synthetic Biology

In this article, we propose a domain specific language, GUBS (Genomic Unified Behavior Specification), dedicated to the behavioral specification of synthetic biological devices, viewed as discrete open dynamical systems. GUBS is a rule-based declarative language. By contrast to a closed system, a program is always a partial description of the behavior of the system. The semantics of the language accounts the existence of some hidden non-specified actions possibly altering the behavior of the programmed device. The compilation framework follows a scheme similar to automatic theorem proving, aiming at improving synthetic biological design safety.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347

Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite

How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies of five isolates, we show they represent three races that are genetically diverged by ∼1%. Despite this divergence, their genomes are mosaic-like, with ∼25% being introgressed from other races. Sequential infection experiments show that infection by adapted races enables subsequent infection of hosts by normally non-infecting races. This facilitates introgression and the exchange of effector repertoires, and may enable the evolution of novel races that can undergo clonal population expansion on new hosts. We discuss recent studies on hybridization in other eukaryotes such as yeast, Heliconius butterflies, Darwin’s finches, sunflowers and cichlid fishes, and the implications of introgression for pathogen evolution in an agro-ecological environment