Node-balancing by edge-increments

Suppose you are given a graph $G=(V,E)$ with a weight assignment $w:V\rightarrow\mathbb{Z}$ and that your objective is to modify $w$ using legal steps such that all vertices will have the same weight, where in each legal step you are allowed to choose an edge and increment the weights of its end points by $1$. In this paper we study several variants of this problem for graphs and hypergraphs. On the combinatorial side we show connections with fundamental results from matching theory such as Hall's Theorem and Tutte's Theorem. On the algorithmic side we study the computational complexity of associated decision problems. Our main results are a characterization of the graphs for which any initial assignment can be balanced by edge-increments and a strongly polynomial-time algorithm that computes a balancing sequence of increments if one exists.Comment: 10 page

Rewriting Systems for Reachability in Vector Addition Systems with Pairs

15 pagesInternational audienceWe adapt hypergraph rewriting system to a generalization of Vector Addition Systems with States (VASS) that we call vector addition systems with pairs (VASP). We give rewriting systems and strategies, that allow us to obtain reachability equivalence results between some classes of VASP and VASS. Reachability for the later is well known be equivalent to reachability in Petri nets. VASP generalize also Branching Extension of VASS (BVASS) for which it is unknown if they are more expressive than VASS. We consider here a more restricted notion of reachability for VASP than that for BVASS. However the reachability decision problem corresponding is already equivalent to decidability of the provability in Multiplicative and Exponential Linear Logic (MELL), a question left open for more than 20 years

Singularly Perturbed Monotone Systems and an Application to Double Phosphorylation Cycles

The theory of monotone dynamical systems has been found very useful in the modeling of some gene, protein, and signaling networks. In monotone systems, every net feedback loop is positive. On the other hand, negative feedback loops are important features of many systems, since they are required for adaptation and precision. This paper shows that, provided that these negative loops act at a comparatively fast time scale, the main dynamical property of (strongly) monotone systems, convergence to steady states, is still valid. An application is worked out to a double-phosphorylation ``futile cycle'' motif which plays a central role in eukaryotic cell signaling.Comment: 21 pages, 3 figures, corrected typos, references remove

Model-Based Verification, Optimization, Synthesis and Performance Evaluation of Real-Time Systems

International audienceThis article aims at providing a concise and precise Travellers Guide, Phrase Book or Reference Manual to the timed automata modeling formalism introduced by Alur and Dill [8, 9]. The paper gives comprehensive definitions of timed automata, priced (or weighted) timed automata, and timed games and highlights a number of results on associated decision problems related to model checking, equivalence checking, optimal scheduling, the existence of winning strategies, and then statistical model checking

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Separation algorithms for 0-1 knapsack polytopes

Valid inequalities for 0-1 knapsack polytopes often prove useful when tackling hard 0-1 Linear Programming problems. To generate such inequalities, one needs separation algorithms for them, i.e., routines for detecting when they are violated. We present new exact and heuristic separation algorithms for several classes of inequalities, namely lifted cover, extended cover, weight and lifted pack inequalities. Moreover, we show how to improve a recent separation algorithm for the 0-1 knapsack polytope itself. Extensive computational results, on MIPLIB and OR Library instances, show the strengths and limitations of the inequalities and algorithms considered