It is increasingly recognized that material surface topography is able to evoke specific cellular responses, endowing materials with instructive properties that were formerly reserved for growth factors. This opens the window to improve upon, in a cost-effective manner, biological performance of any surface used in the human body. Unfortunately, the interplay between surface topographies and cell behavior is complex and still incompletely understood. Rational approaches to search for bioactive surfaces will therefore omit previously unperceived interactions. Hence, in the present study, we use mathematical algorithms to design nonbiased, random surface features and produce chips of poly(lactic acid) with 2,176 different topographies. With human mesenchymal stromal cells (hMSCs) grown on the chips and using high-content imaging, we reveal unique, formerly unknown, surface topographies that are able to induce MSC proliferation or osteogenic differentiation. Moreover, we correlate parameters of the mathematical algorithms to cellular responses, which yield novel design criteria for these particular parameters. In conclusion, we demonstrate that randomized libraries of surface topographies can be broadly applied to unravel the interplay between cells and surface topography and to find improved material surfaces.

The minimum-cost flow problem is a classic problem in combinatorial optimization with various applications. Several pseudo-polynomial, polynomial, and strongly polynomial algorithms have been developed in the past decades, and it seems that both the problem and the algorithms are well understood. However, some of the algorithms' running times observed in empirical studies contrast the running times obtained by worst-case analysis not only in the order of magnitude but also in the ranking when compared to each other. For example, the Successive Shortest Path (SSP) algorithm, which has an exponential worst-case running time, seems to outperform the strongly polynomial Minimum-Mean Cycle Canceling algorithm. To explain this discrepancy, we study the SSP algorithm in the framework of smoothed analysis and establish a bound of O(mnφ(m + n log n)) for its smoothed running time. This shows that worst-case instances for the SSP algorithm are not robust and unlikely to be encountered in practice.

Finding a d-regular spanning subgraph (or d-factor) of a graph is easy by Tutte's reduction to the matching problem. By the same reduction, it is easy to find a minimal or maximal d-factor of a graph. However, if we require that the d-factor is connected, these problems become NP-hard -finding a minimal connected 2-factor is just the traveling salesman problem (TSP).Given a complete graph with edge weights that satisfy the triangle inequality, we consider the problem of finding a minimal connected d-factor. We give a 3-approximation for all d and improve this to an (r + 1)-approximation for even d, where r is the approximation ratio of the TSP. This yields a 2.5-approximation for even d. The same algorithm yields an (r+1)-approximation for the directed version of the problem, where r is the approximation ratio of the asymmetric TSP. We also show that none of these minimization problems can be approximated better than the corresponding TSP.Finally, for the decision problem of deciding whether a given graph contains a connected d-factor, we extend known hardness results.

Finding low-cost spanning subgraphs with given degree and connectivity requirements is a fundamental problem in the area of network design. We consider the problem of finding d-regular spanning subgraphs (or d-factors) of minimum weight with connectivity requirements. For the case of k-edge-connectedness, we present approximation algorithms that achieve constant approximation ratios for all d ≥ 2 · k/2 . For the case of k-vertex-connectedness, we achieve constant approximation ratios for d ≥ 2k−1. Our algorithms also work for arbitrary degree sequences if the minimum degree is at least 2 · k/2 (for k-edge-connectivity) or 2k − 1 (for k-vertex-connectivity). To complement our approximation algorithms, we prove Syst (2018) 62:441-464 that the problem with simple connectivity cannot be approximated better than the traveling salesman problem. In particular, the problem is APX-hard.

Belief propagation (BP) is a message-passing heuristic for statistical inference in graphical models such as Bayesian networks and Markov random fields. BP is used to compute marginal distributions or maximum likelihood assignments and has applications in many areas, including machine learning, image processing, and computer vision. However, the theoretical understanding of the performance of BP remains limited.Recently, BP has been applied to combinatorial optimization problems. It has been proved that BP can be used to compute maximum-weight matchings and minimum-cost flows for instances with a unique optimum. The number of iterations needed for this is pseudo-polynomial and hence BP is not efficient in general.We study BP in the framework of smoothed analysis and prove that with high probability the number of iterations needed to compute maximum-weight matchings and minimum-cost flows is bounded by a polynomial if the weights/costs of the edges are randomly perturbed. To prove our upper bounds, we use an isolation lemma by Beier and Vöcking (SIAM Journal on Computing, 2006) for the matching problem and we generalize an isolation lemma by Gamarnik, Shah, and Wei (Operations Research, 2012) for the min-cost flow problem. We also prove lower tail bounds for the number of iterations that BP needs to converge that almost match our upper bounds. Belief PropagationThe belief propagation (BP) algorithm is a message-passing algorithm that is used for solving probabilistic inference problems on graphical models. It was proposed by Pearl in 1988 [9]. Typical graphical models to which BP is applied are Bayesian networks and Markov random fields. There are two variants of BP. The sum-product variant is used to compute marginal probabilities. The max-product variant (or the functionally equivalent min-sum variant) is used to compute maximum a posteriori (MAP) probability estimates.