Identification of control targets in Boolean molecular network models via computational algebra

Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. Experimentally, node manipulation requires technology to completely repress or fully activate a particular gene product while edge manipulations only require a drug that inactivates the interaction between two gene products. Results: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network.Comment: 12 pages, 4 figures, 2 table

Covering matroid

In this paper, we propose a new type of matroids, namely covering matroids, and investigate the connections with the second type of covering-based rough sets and some existing special matroids. Firstly, as an extension of partitions, coverings are more natural combinatorial objects and can sometimes be more efficient to deal with problems in the real world. Through extending partitions to coverings, we propose a new type of matroids called covering matroids and prove them to be an extension of partition matroids. Secondly, since some researchers have successfully applied partition matroids to classical rough sets, we study the relationships between covering matroids and covering-based rough sets which are an extension of classical rough sets. Thirdly, in matroid theory, there are many special matroids, such as transversal matroids, partition matroids, 2-circuit matroid and partition-circuit matroids. The relationships among several special matroids and covering matroids are studied.Comment: 15 page

Bounds on the shear load of cohesionless granular matter

We characterize the force state of shear-loaded granular matter by relating the macroscopic stress to statistical properties of the force network. The purely repulsive nature of the interaction between grains naturally provides an upper bound for the sustainable shear stress, which we analyze using an optimization procedure inspired by the so-called force network ensemble. We establish a relation between the maximum possible shear resistance and the friction coefficient between individual grains, and find that anisotropies of the contact network (or the fabric tensor) only have a subdominant effect. These results can be considered the hyperstatic limit of the force network ensemble and we discuss possible implications for real systems. Finally, we argue how force anisotropies can be related quantitatively to experimental measurements of the effective elastic constants.Comment: 17 pages, 6 figures. v2: slightly rearranged, introduction and discussion rewritte