Robert Weismantel

A logical model provides insights into T cell receptor signaling

Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co-receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well-established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies) and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications.

Cutting planes in integer and mixed integer programming

This survey presents cutting planes that are useful or potentially useful in solving mixed integer programs. Valid inequalities for (i) general integer programs, (ii) problems with local structure such as knapsack constraints, and (iii) problems with 0-1 coefficient matrices, such as set packing, are examined in turn. Finally, the use of valid inequalities for classes of problems with structure, such as network design, is explored.

Inequalities from Two Rows of a Simplex Tableau

In this paper we explore the geometry of the integer points in a cone rooted at a rational point. This basic geometric object allows us to establish some links between lattice point free bodies and the derivation of inequalities for mixed integer linear programs by considering two rows of a simplex tableau simultaneously.

Nonlinear Integer Programming

Research efforts of the past fifty years have led to a development of linear integer programming as a mature discipline of mathematical optimization. Such a level of maturity has not been reached when one considers nonlinear systems subject to integrality requirements for the variables. This chapter is dedicated to this topic. The primary goal is a study of a simple version of general nonlinear integer problems, where all constraints are still linear. Our focus is on the computational complexity of the problem, which varies significantly with the type of nonlinear objective function in combination with the underlying combinatorial structure. Numerous boundary cases of complexity emerge, which sometimes surprisingly lead even to polynomial time algorithms.We also cover recent successful approaches for more general classes of problems. Though no positive theoretical efficiency results are available, nor are they likely to ever be available, these seem to be the currently most successful and interesting approaches for solving practical problems. It is our belief that the study of algorithms motivated by theoretical considerations and those motivated by our desire to solve practical instances should and do inform one another. So it is with this viewpoint that we present the subject, and it is in this direction that we hope to spark further research.

On the 0/1 knapsack polytope

This paper deals with the 0/1 knapsack polytope. In particular, we introduce the class ofweight inequalities. This class of inequalities is needed to describe the knapsack polyhedron when the weights of the items lie in certain intervals. A generalization of weight inequalities yields the so-called “weight-reduction principle” and the class of extended weight inequalities. The latter class of inequalities includes minimal cover and (l,k)-configuration inequalities. The properties of lifted minimal cover inequalities are extended to this general class of inequalities.

A Semidefinite Programming Approach to the Quadratic Knapsack Problem

In order to gain insight into the quality of semidefinite relaxations of constrained quadratic 0/1 programming problems we study the quadratic knapsack problem. We investigate several basic semidefinite relaxations of this problem and compare their strength in theory and in practice. Various possibilities to improve these basic relaxations by cutting planes are discussed. The cutting planes either arise from quadratic representations of linear inequalities or from linear inequalities in the quadratic model. In particular, a large family of combinatorial cuts is introduced for the linear formulation of the knapsack problem in quadratic space. Computational results on a small class of practical problems illustrate the quality of these relaxations and cutting planes.

Packing Steiner trees: a cutting plane algorithm and computational results

In this paper we describe a cutting plane algorithm for the Steiner tree packing problem. We use our algorithm to solve some switchbox routing problems of VLSI-design and report on our computational experience. This includes a brief discussion of separation algorithms, a new LP-based primal heuristic and implementation details. The paper is based on the polyhedral theory for the Steiner tree packing polyhedron developed in our companion paper (this issue) and meant to turn this theory into an algorithmic tool for the solution of practical problems.

Solving Multiple Knapsack Problems by Cutting Planes

In this paper we consider the multiple knapsack problem, which is defined as follows: given a set

N-fold integer programming

N

The Steiner tree packing problem in VLSI design

of items with weights