A matheuristic approach for the Pollution-Routing Problem

This paper deals with the Pollution-Routing Problem (PRP), a Vehicle Routing Problem (VRP) with environmental considerations, recently introduced in the literature by [Bektas and Laporte (2011), Transport. Res. B-Meth. 45 (8), 1232-1250]. The objective is to minimize operational and environmental costs while respecting capacity constraints and service time windows. Costs are based on driver wages and fuel consumption, which depends on many factors, such as travel distance and vehicle load. The vehicle speeds are considered as decision variables. They complement routing decisions, impacting the total cost, the travel time between locations, and thus the set of feasible routes. We propose a method which combines a local search-based metaheuristic with an integer programming approach over a set covering formulation and a recursive speed-optimization algorithm. This hybridization enables to integrate more tightly route and speed decisions. Moreover, two other "green" VRP variants, the Fuel Consumption VRP (FCVRP) and the Energy Minimizing VRP (EMVRP), are addressed. The proposed method compares very favorably with previous algorithms from the literature and many new improved solutions are reported.Comment: Working Paper -- UFPB, 26 page

Mathematical Models and Search Algorithms for the Capacitated p-Center Problem

The capacitated p-center problem requires one to select p facilities from a set of candidates to service a number of customers, subject to facility capacity constraints, with the aim of minimizing the maximum distance between a customer and its associated facility. The problem is well known in the field of facility location, because of the many applications that it can model. In this paper, we solve it by means of search algorithms that iteratively seek the optimal distance by solving tailored subproblems. We present different mathematical formulations for the subproblems and improve them by means of several valid inequalities, including an effective one based on a 0–1 disjunction and the solution of subset sum problems. We also develop an alternative search strategy that finds a balance between traditional sequential search and binary search. This strategy limits the number of feasible subproblems to be solved and, at the same time, avoids large overestimates of the solution value, which are detrimental for the search. We evaluate the proposed techniques by means of extensive computational experiments on benchmark instances from the literature and new larger test sets. All instances from the literature with up to 402 vertices and integer distances are solved to proven optimality, including 13 open cases, and feasible solutions are found in 10 minutes for instances with up to 3,038 vertices

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin