• The Inria's Research Teams produce an annual Activity Report presenting their activities and their results of the year. These reports include the team members, the scientific program, the software developed by the team and the new results of the year. The report also describes the grants, contracts and the activities of dissemination and teaching. Finally, the report gives the list of publications of the year.

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## Section: Highlights of the Year

### Highlights of the Year

• Multistationarity Analysis in CRNs

The non-existence of multiple steady states in very large chemical reaction networks, out of reach of symbolic computation methods, can be predicted by a remarkably fast graph rewriting algorithm, based on Soliman 2013's theorem (Sylvain Soliman. A stronger necessary condition for the multistationarity of chemical reaction networks. Bulletin of Mathematical Biology, 75(11):2289–2303, 2013.). Study published in the Journal of Theoretical Biology [1] (graphical abstract in Fig. 1).

Figure 1. Graphical abstract of [1].
• Distinguishing resistence from resilience to prolong antibiotic potency

Biomedical engineers at Duke University, in collaboration with Grégory Batt and Virgile Andréani, have shown experimentally that there is more than one flavor of antibiotic resistance and that it could – and should – be taken advantage of to keep first-line antibiotics in our medical arsenal. While an individual bacterium can be resistant to antibiotics, resilience only arises within a community. This happens when bacterial cells produce enough beta-lactamases to degrade the antibiotics, but not enough to save themselves from the initial onslaught. As some cells die and release more and more of the enzyme, the population as a whole eventually rids their environment of the antibiotic. Study published in Science Advances [6].

• Biochemical Programs in Synthetic Cell-like Microreactors

Researchers at Lab. CNRS-ALCEDIAG Sys2Diag in Montpellier, in collaboration with François Fages, have shown that an algorithm for the differential diagnosis of diabetes can be specified by three Boolean circuits and robustly implemented with real enzymes encapsulated in artificial vesicles that become fluorescent according to 5 different forms of diabetes. The robustness of the circuit was optimized in BIOCHAM by optimizing the initial concentrations of the enzymes with respect to a behavior specification in quantitative temporal logic. The protocells built with a microfluidic device were validated on a cohorte of patients' urines from Montpellier's Hospital. Study published in Molecular Systems Biology [3] (see Fig. 2).

Figure 2. Artistic illustration by Courbet in cover page of Molecular Systems Biology [3].

#### Awards

• La Recherche magazine 2019 Award - mention Information Sciences

The article${}^{6}$ “Strong Turing Completeness of Continuous Chemical Reaction Networks and Compilation of Mixed Analog-Digital Programs” by F. Fages, G. Le Guludec, O. Bournez and A. Pouly, presented and awarded Best Paper at CMSB'17 last year has received the 2019 Award of magazine “La Recherche” - in Information Sciences.