A computational model of gene expression in an inducible synthetic circuit

Synthetic biology aims to the rational design of gene circuits with predictable behaviours. Great efforts have been done so far to introduce in the field mathematical models that could facilitate the design of synthetic networks. Here we present a mathematical model of a synthetic gene-circuit with a negative feedback. The closed loop configuration allows the control of transcription by an inducer molecule (IPTG). Escherichia coli bacterial cells were transformed and expression of a fluorescent reporter (GFP) was measured for different inducer levels. Computer model simulations well reproduced the experimental induction data, using a single fitting parameter. Independent genetic components were used to assemble the synthetic circuit. The mathematical model here presented could be useful to predict how changes in these genetic components affect the behaviour of the synthetic circuit

A branch-and-price algorithm for the temporal bin packing problem

We study an extension of the classical Bin Packing Problem, where each item consumes the bin capacity during a given time window that depends on the item itself. The problem asks for finding the minimum number of bins to pack all the items while respecting the bin capacity at any time instant. A polynomial-size formulation, an exponential-size formulation, and a number of lower and upper bounds are studied. A branch-and-price algorithm for solving the exponential-size formulation is introduced. An overall algorithm combining the different methods is then proposed and tested through extensive computational experiments

Approximated Perspective Relaxations: a Project&Lift Approach

The Perspective Reformulation (PR) of a Mixed-Integer NonLinear Program with semi-continuous variables is obtained by replacing each term in the (separable) objective function with its convex envelope. Solving the corresponding continuous relaxation requires appropriate techniques. Under some rather restrictive assumptions, the Projected PR (P^2R) can be defined where the integer variables are eliminated by projecting the solution set onto the space of the continuous variables only. This approach produces a simple piecewise-convex problem with the same structure as the original one; however, this prevents the use of general-purpose solvers, in that some variables are then only implicitly represented in the formulation. We show how to construct an Approximated Projected PR (AP^2R) whereby the projected formulation is "lifted" back to the original variable space, with each integer variable expressing one piece of the obtained piecewise-convex function. In some cases, this produces a reformulation of the original problem with exactly the same size and structure as the standard continuous relaxation, but providing substantially improved bounds. In the process we also substantially extend the approach beyond the original P^2R development by relaxing the requirement that the objective function be quadratic and the left endpoint of the domain of the variables be non-negative. While the AP^2R bound can be weaker than that of the PR, this approach can be applied in many more cases and allows direct use of off-the-shelf MINLP software; this is shown to be competitive with previously proposed approaches in some applications

Casting Light on the Hidden Bilevel Combinatorial Structure of the Capacitated Vertex Separator Problem

Given an undirected graph, we study the capacitated vertex separator problem that asks to find a subset of vertices of minimum cardinality, the removal of which induces a graph having a bounded number of pairwise disconnected shores (subsets of vertices) of limited cardinality. The problem is of great importance in the analysis and protection of communication or social networks against possible viral attacks and for matrix decomposition algorithms. In this article, we provide a new bilevel interpretation of the problem and model it as a two-player Stackelberg game in which the leader interdicts the vertices (i.e., decides on the subset of vertices to remove), and the follower solves a combinatorial optimization problem on the resulting graph. This approach allows us to develop a computational framework based on an integer programming formulation in the natural space of the variables. Thanks to this bilevel interpretation, we derive three different families of strengthening inequalities and show that they can be separated in polynomial time. We also show how to extend these results to a min-max version of the problem. Our extensive computational study conducted on available benchmark instances from the literature reveals that our new exact method is competitive against the state-of-the-art algorithms for the capacitated vertex separator problem and is able to improve the best-known results for several difficult classes of instances. The ideas exploited in our framework can also be extended to other vertex/edge deletion/ insertion problems or graph partitioning problems by modeling them as two-player Stackel- berg games and solving them through bilevel optimization

CliSAT: A new exact algorithm for hard maximum clique problems

Given a graph, the maximum clique problem (MCP) asks for determining a complete subgraph with the largest possible number of vertices. We propose a new exact algorithm, called CliSAT , to solve the MCP to proven optimality. This problem is of fundamental importance in graph theory and combinatorial optimization due to its practical relevance for a wide range of applications. The newly developed exact approach is a combinatorial branch-and-bound algorithm that exploits the state-of-the-art branching scheme enhanced by two new bounding techniques with the goal of reducing the branching tree. The first one is based on graph colouring procedures and partial maximum satisfiability problems arising in the branching scheme. The second one is a filtering phase based on constraint programming and domain propagation techniques. CliSAT is designed for structured MCP instances which are computationally difficult to solve since they are dense and contain many interconnected large cliques. Extensive experiments on hard benchmark instances, as well as new hard instances arising from different applications, show that CliSAT outperforms the state-of-the-art MCP algorithms, in some cases by several orders of magnitude

A combinatorial flow-based formulation for temporal bin packing problems

We consider two neighboring generalizations of the classical bin packing problem: the temporal bin packing problem (TBPP) and the temporal bin packing problem with fire-ups (TBPP-FU). In both cases, the task is to arrange a set of given jobs, characterized by a resource consumption and an activity window, on homogeneous servers of limited capacity. To keep operational costs but also energy consumption low, TBPP is concerned with minimizing the number of servers in use, whereas TBPP-FU additionally takes into account the switch-on processes required for their operation. Either way, challenging integer optimization problems are obtained, which can differ significantly from each other despite the seemingly only marginal variation of the problems. In the literature, a branch-and-price method enriched with many preprocessing steps (for TBPP) and compact formulations (for TBPP-FU), benefiting from numerous reduction methods, have emerged as, currently, the most promising solution methods. In this paper, we introduce, in a sense, a unified solution framework for both problems (and, in fact, a wide variety of further interval scheduling applications) based on graph theory. Any scientific contributions in this direction failed so far because of the exponential size of the associated networks. The approach we present in this article does not change the theoretical exponentiality itself, but it can make it controllable by clever construction of the resulting graphs. In particular, for the first time all classical benchmark instances (and even larger ones) for the two problems can be solved – in times that significantly improve those of the previous approaches

A numerical solver of 3D Poisson Nernst Planck equations for functional studies of ion channels

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