A New General-Purpose Algorithm for Mixed-Integer Bilevel Linear Programs

Bilevel optimization problems are very challenging optimization models arising in many important practical contexts, including pricing mechanisms in the energy sector, airline and telecommunication industry, transportation networks, critical infrastructure defense, and machine learning. In this paper, we consider bilevel programs with continuous and discrete variables at both levels, with linear objectives and constraints (continuous upper level variables, if any, must not appear in the lower level problem). We propose a general-purpose branch-and-cut exact solution method based on several new classes of valid inequalities, which also exploits a very effective bilevel-specific preprocessing procedure. An extensive computational study is presented to evaluate the performance of various solution methods on a common testbed of more than 800 instances from the literature and 60 randomly generated instances. Our new algorithm consistently outperforms (often by a large margin) alternative state-of-the-art methods from the literature, including methods exploiting problem-specific information for special instance classes. In particular, it solves to optimality more than 300 previously unsolved instances from the literature. To foster research on this challenging topic, our solver is made publicly available online

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

Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker

An (MI)LP-based Primal Heuristic for 3-Architecture Connected Facility Location in Urban Access Network Design

We investigate the 3-architecture Connected Facility Location Problem arising in the design of urban telecommunication access networks. We propose an original optimization model for the problem that includes additional variables and constraints to take into account wireless signal coverage. Since the problem can prove challenging even for modern state-of-the art optimization solvers, we propose to solve it by an original primal heuristic which combines a probabilistic fixing procedure, guided by peculiar Linear Programming relaxations, with an exact MIP heuristic, based on a very large neighborhood search. Computational experiments on a set of realistic instances show that our heuristic can find solutions associated with much lower optimality gaps than a state-of-the-art solver.Comment: This is the authors' final version of the paper published in: Squillero G., Burelli P. (eds), EvoApplications 2016: Applications of Evolutionary Computation, LNCS 9597, pp. 283-298, 2016. DOI: 10.1007/978-3-319-31204-0_19. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-31204-0_1

Health care in Bosnia and Herzegovina before, during, and after 1992–1995 war: a personal testimony

Market-based health care reform during democratic transition in Bosnia and Herzegovina was complicated by the 1992–1995 war, that devastated the country and greater part of its health care infrastructure. The course of the transition and consequences of war for the health system and health professionals are presented here from the perspective of the author. The description of real-life situations and their context is used to illustrate the problems physicians, as well as international community, were faced with and how they tried to cope with them during and after the war. Speaking openly about the mistakes that were made in those times is the first step in preventing them from happening again and an invitation for exchange of opinions and open academic discussion

Molecular profiling of cervical cancer progression

Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up- and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-β) were upregulated at least two-fold. Some of these genes (AKT and MMP3) are key regulators of epithelial–mesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer