Discrete graphical models (also known as discrete Markov random fields) are a major conceptual tool to model the structure of optimization problems in computer vision. While in the last decade research has focused on fast approximative methods, algorithms that provide globally optimal solutions have come more into the research focus in the last years. However, large scale computer vision problems seemed to be out of reach for such methods. In this paper we introduce a promising way to bridge this gap based on partial optimality and structural properties of the underlying problem factorization. Combining these preprocessing steps, we are able to solve grids of size 2048×2048 in less than 90 seconds. On the hitherto unsolvable Chinese character dataset of Nowozin et. al we obtain provably optimal results in 56% of the instances and achieve competitive runtimes on other recent benchmark problems. While in the present work only generalized Potts models are considered, an extension to general graphical models seems to be feasible.

MOTIVATION: Gene expression profiling by microarrays or transcript sequencing enables observing the pathogenic function of tumors on a mesoscopic level. RESULTS: We investigated neuroblastoma tumors that clinically exhibit a very heterogeneous course ranging from rapid growth with fatal outcome to spontaneous regression and detected regulatory oncogenetic shifts in their metabolic networks. In contrast to common enrichment tests, we took network topology into account by applying adjusted wavelet transforms on an elaborated and new 2D grid representation of curated pathway maps from the Kyoto Enzyclopedia of Genes and Genomes. The aggressive form of the tumors showed regulatory shifts for purine and pyrimidine biosynthesis as well as folate-mediated metabolism of the one-carbon pool in respect to increased nucleotide production. We spotted an oncogentic regulatory switch in glutamate metabolism for which we provided experimental validation, being the first steps towards new possible drug therapy. The pattern recognition method we used complements normal enrichment tests to detect such functionally related regulation patterns. AVAILABILITY AND IMPLEMENTATION: PathWave is implemented in a package for R (www.r-project.org) version 2.6.0 or higher. It is freely available from http://www.ichip.de/software/pathwave.html.

BACKGROUND: The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable. RESULTS: We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed. CONCLUSIONS: Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters, which holds interesting prospects for experimental design purposes.

In 1996 Ivkovič and Lloyd [A fundamental restriction on fully dynamic maintenance of bin packing, Inform. Process. Lett., 59 (1996), pp. 229–232] gave the lower bound $\frac{4}{3}$ on the asymptotic worst-case ratio for so-called fully dynamic bin packing algorithms, where the number of repackable items in each step is restricted by a constant. In this paper we improve this result to about $1.3871$. We present our proof for a semionline case of the classical bin packing, but it works for fully dynamic bin packing as well. We prove the lower bound by analyzing and solving a specific optimization problem. The bound can be expressed exactly using the Lambert W function.

The famous Padberg–Rao separation algorithm for b-matching polyhedra can be implemented to run in $\mathcal{O}(|V|^2|E|\log(|V|^2/|E|))$ time in the uncapacitated case, and in $\mathcal{O}(|V||E|^2\log(|V|^2/|E|))$ time in the capacitated case. We give a new and simple algorithm for the capacitated case which can be implemented to run in $\mathcal{O}(|V|^2|E|\log(|V|^2/|E|))$ time.

BACKGROUND: Microarray technology produces gene expression data on a genomic scale for an endless variety of organisms and conditions. However, this vast amount of information needs to be extracted in a reasonable way and funneled into manageable and functionally meaningful patterns. Genes may be reasonably combined using knowledge about their interaction behaviour. On a proteomic level, biochemical research has elucidated an increasingly complete image of the metabolic architecture, especially for less complex organisms like the well studied bacterium Escherichia coli. RESULTS: We sought to discover central components of the metabolic network, regulated by the expression of associated genes under changing conditions. We mapped gene expression data from E. coli under aerobic and anaerobic conditions onto the enzymatic reaction nodes of its metabolic network. An adjacency matrix of the metabolites was created from this graph. A consecutive ones clustering method was used to obtain network clusters in the matrix. The wavelet method was applied on the adjacency matrices of these clusters to collect features for the classifier. With a feature extraction method the most discriminating features were selected. We yielded network sub-graphs from these top ranking features representing formate fermentation, in good agreement with the anaerobic response of hetero-fermentative bacteria. Furthermore, we found a switch in the starting point for NAD biosynthesis, and an adaptation of the l-aspartate metabolism, in accordance with its higher abundance under anaerobic conditions. CONCLUSION: We developed and tested a novel method, based on a combination of rationally chosen machine learning methods, to analyse gene expression data on the basis of interaction data, using a metabolic network of enzymes. As a case study, we applied our method to E. coli under oxygen deprived conditions and extracted physiologically relevant patterns that represent an adaptation of the cells to changing environmental conditions. In general, our concept may be transferred to network analyses on biological interaction data, when data for two comparable states of the associated nodes are made available.

This paper makes a contribution to the branch and cut approach to the capacitated vehicle-routing problem (CVRP). In the CVRP, the demands of a set of customers have to be met at minimum total travel cost using vehicles of identical capacity based at a single depot. The potential of maximally violated mod-p cutting-planes (Caprara et al. 2000) for the CVRP is investigated via a computational study. The foundation of the assessment is formed by classes of problem-specific constraints taken from the literature. In several separation algorithms for the CVRP, it is advantageous to shrink inclusionwise maximal minimum-weight cuts in support graphs as preprocessing. It is mentioned how a partition of the set of customers into such mincuts can be computed in a fast and elegant way using the mincut algorithm of Hao and Orlin (1994). Interestingly, maximally violated mod-p cuts, which are general-purpose cuts of Chvátal-Gomory type, stand comparison with problem-specific cuts for the CVRP and they are clearly useful on top of such cuts. The first-time proven optimal solution of the CVRP instance B-n68-k9 is reported. The computation used a branching strategy with far lookahead and relied on maximally violated mod-p cuts. This paper on maximally violated cuts belongs to a set of papers originating from Applegate et al. (1995) where a separation of maximally violated combs for the traveling-salesman problem (TSP) is suggested.

A fundamental problem in computational biology is the construction of physical maps of chromosomes from hybridiz;c tion experiments between unique probes and clones of chromosome fragments in the presence of error.Alizadeh, Karp, Weisser and Zweig (AKWZ94] first considered a maximumlikelihood model of the problem that is equivalent to finding an o&ring of the probes that minimizes a weighted sum of errors, and developed several effective heuristics.We show that by exploiting information about the endprobes of clones, this model can be formulated as a weighted Betweenness Problem.Thii affords the signiicant advautage of allowing the well-developed tools of integer lmearprogramming aud branch-and-cut algorithms to be brought to bear on physical mapping, enabling us for the first time to solve small mapping instances to optima&y even in the presence of high error.We also show that by combining the optimal solution of many small overlapping Betweenness Problems, one can effectively screen errors from larger instances, and solve the edited instance to optimality as a Hamming-Distance Traveling Salesman Problem.This suggests a new combined approach to physical map construction.

Very frequently in practical applications we are faced with large or very large scale traveling salesman problems where the number of cities may range from several hundreds or thousands up to even millions. Due to timing restrictions in the production process there may be situations where good approximative solutions to an instance of the traveling salesman problem have to be found very fast, and where it is not feasible to call even O(n2) time procedures too often. In this paper we discuss several ideas to handle such large traveling salesman problems under time restrictions. We will consider Euclidean traveling salesman problems in the plane and show how their geometric structure can be exploited to derive fast heuristics. INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.

This paper contains the description of a traveling salesman problem library (TSPLIB) which is meant to provide researchers with a broad set of test problems from various sources and with various properties. For every problem a short description is given along with known lower and upper bounds. Several references to computational tests on some of the problems are given. INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.