Branch-and-Cut for the split delivery vehicle routing problem with time windows

The split delivery vehicle routing problem with time windows (SDVRPTW) is a notoriously hard combinatorial optimization problem. First, it is hard to find a useful compact mixed-integer programming (MIP) formulation for the SDVRPTW. Standard modeling approaches either suffer from inherent symmetries (mixed-integer programs with a vehicle index) or cannot exactly capture all aspects of feasibility. Because of the possibility to visit customers more than once, the standard mechanisms to propagate load and time along the routes fail. Second, the lack of useful formulations has rendered any direct MIP-based approach impossible. Up to now, the most effective exact algorithms for the SDVRPTW have been branch-and-price-and-cut approaches using path-based formulations. In this paper, we propose a new and tailored branch-and-cut algorithm to solve the SDVRPTW. It is based on a new, relaxed compact model, in which some integer solutions are infeasible for the SDVRPTW. We use known and introduce some new classes of valid inequalities to cut off such infeasible solutions. One new class is path-matching constraints that generalize infeasible-path constraints. However, even with the valid inequalities, some integer solutions to the new compact formulation remain to be tested for feasibility. For a given integer solution, we build a generally sparse subnetwork of the original instance. On this subnetwork, all time-window-feasible routes can be enumerated, and a path-based residual problem then solved to decide on the selection of routes, the delivery quantities, and thereby the overall feasibility. All infeasible solutions need to be cut off. For this reason, we derive some strengthened feasibility cuts exploiting the fact that solutions often decompose into clusters. Computational experiments show that the new approach is able to prove optimality for several previously unsolved instances from the literature

The Split Delivery Vehicle Routing Problem with Time Windows and Customer Inconvenience Constraints

In classical routing problems, each customer is visited exactly once. By contrast, when allowing split deliveries, customers may be served through multiple visits. This potentially results in substantial savings in travel costs. Even if split deliveries are beneficial to the transport company, several visits may be undesirable on the customer side: at each visit the customer has to interrupt his primary activities and handle the goods receipt. The contribution of the present paper consists in a thorough analysis of the possibilities and limitations of split delivery distribution strategies. To this end, we investigate two different types of measures for limiting customer inconvenience (a maximum number of visits and the temporal synchronization of deliveries) and evaluate the impact of these measures on carrier efficiency by means of different objective functions (comprising variable routing costs, costs related to route durations, fixed fleet costs). We consider the vehicle routing problem with time windows in which split deliveries are allowed (SDVRPTW) and define the corresponding generalization that takes into account customer inconvenience constraints (SDVRPTW-IC). We design an extended branch-and-cut algorithm to solve the SDVRPTW-IC and report on experimental results showing the impact of customer inconvenience constraints. We finally draw useful insights for logistics managers on the basis of the experimental analysis carried out

A Branch-Price-and-Cut Algorithm for the Capacitated Multiple Vehicle Traveling Purchaser Problem with Unitary Demand

The multiple vehicle traveling purchaser problem (MVTPP) consists of simultaneously selecting suppliers and routing a fleet of homogeneous vehicles to purchase different products at the selected suppliers so that all product demands are fulfilled and traveling and purchasing costs are minimized. We consider variants of the MVTPP in which the capacity of the vehicles can become binding and the demand for each product is one unit. Corresponding solution algorithms from the literature are either branch-and-cut or branch-and-price algorithms, where in the latter case the route-generation subproblem is solved on an expanded graph by applying standard dynamic-programming techniques. Our branch-price-and-cut algorithm employs a novel labeling algorithm that works directly on the original network and postpones the purchasing decisions until the route has been completely defined. Moreover, we define a new branching rule generally applicable in case of unitary product demands, introduce a new family of valid inequalities to apply when suppliers can be visited at most once, and show how product incompatibilities can be handled without considering additional resources in the pricing problem. In comprehensive computational experiments with standard benchmark sets we prove that the new branch-price-and-cut approach is highly competitive

Non-Coding RNA and Tumor Development in Neurofibromatosis Type 1: ANRIL Rs2151280 Is Associated with Optic Glioma Development and a Mild Phenotype in Neurofibromatosis Type 1 Patients

Non-coding RNAs (ncRNAs) are known to regulate gene expression at the transcriptional and post-transcriptional levels, chromatin remodeling, and signal transduction. The identification of different species of ncRNAs, microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs)-and in some cases, their combined regulatory function on specific target genes-may help to elucidate their role in biological processes. NcRNAs' deregulation has an impact on the impairment of physiological programs, driving cells in cancer development. We here carried out a review of literature concerning the implication of ncRNAs on tumor development in neurofibromatosis type 1 (NF1), an inherited tumor predisposition syndrome. A number of miRNAs and a lncRNA has been implicated in NF1-associated tumors, such as malignant peripheral nerve sheath tumors (MPNSTs) and astrocytoma, as well as in the pathognomonic neurofibromas. Some authors reported that the lncRNA ANRIL was deregulated in the blood of NF1 patients with plexiform neurofibromas (PNFs), even if its role should be further elucidated. We here provided original data concerning the association of a specific genotype about ANRIL rs2151280 with the presence of optic gliomas and a mild expression of the NF1 phenotype. We also detected the LOH of ANRIL in different tumors from NF1 patients, supporting the involvement of ANRIL in some NF1-associated tumors. Our results suggest that ANRIL rs2151280 may be a potential diagnostic and prognostic marker, addressing early diagnosis of optic glioma and predicting the phenotype severity in NF1 patients

Branch-and-Price-and-Cut for the Active-Passive Vehicle-Routing Problem

This paper presents a branch-And-price-And-cut algorithm for the exact solution of the active-passive vehicle-routing problem (APVRP). The APVRP covers a range of logistics applications where pickup-And-delivery requests necessitate a joint operation of active vehicles (e.g., trucks) and passive vehicles (e.g., loading devices such as containers or swap bodies). The objective is to minimize aweighted sum of the total distance traveled, the total completion time of the routes, and the number of unserved requests. To this end, the problem supports a flexible coupling and decoupling of active and passive vehicles at customer locations. Accordingly, the operations of the vehicles have to be synchronized carefully in the planning. The contribution of the paper is twofold: First, we present an exact branch-And-price-And-cut algorithm for this class of routing problems with synchronization constraints. To our knowledge, this algorithm is the first such approach that considers explicitly the temporal interdependencies between active and passive vehicles. The algorithm is based on a nontrivial network representation that models the logical relationships between the different transport tasks necessary to fulfill a request as well as the synchronization of the movements of active and passive vehicles. Second, we contribute to the development of branch-And-price methods in general, in that we solve, for the first time, an ng-path relaxation of a pricing problem with linear vertex costs by means of a bidirectional labeling algorithm. Computational experiments show that the proposed algorithm delivers improved bounds and solutions for a number of APVRP benchmark instances. It is able to solve instances with up to 76 tasks, four active, and eight passive vehicles to optimality within two hours of CPU time

Interference and level of economic damage of Alexandergrass on corn.

O objetivo deste trabalho foi avaliar a competitividade e determinar o nível de dano econômico de papuã infestante da cultura do milho. Os tratamentos foram compostos por densidades de milho (2,60; 3,10; 3,65; 4,00; e 4,80 plantas m-1)e dez populações de papuã para cada densidade de semeadura da cultura. Como indicadores de infestação, avaliou-se a população de plantas, área foliar, cobertura de solo e massa seca da parte aérea de papuã. A massa seca da parte aérea do papuã apresentou melhor ajuste ao modelo da hipérbole retangular e às perdas de produtividade de grãos, devido à interferência da planta daninha estimada satisfatoriamente por esse modelo. A semeadura das densidades de milho de 2,60;3,10 e 3,65 plantas m-1 de todas as características avaliadas foram mais competitivas do que as demais na presença do papuã. A semeadura das densidades de 2,60, 3,10 e 3,65 plantas m-1 aumentou o nível de dano econômico, justificando a adoção de medidas de controle do papuã nas populações mais elevadas. Os valores de NDE variaram de 1,58 a 9,37 plantas m-2 para as densidades de 4,00 e4,80 plantas m-1 de milho, as quais foram menos competitivas com o papuã

Abnormal DNA Methylation Induced by Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells

Background CD 34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be "memorized" by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord-blood-derived CD 34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal-cell-derived factor 1 alpha and reduced protein and mRNA expression of the C-X-C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high-glucose CD 34+ stem cells that negatively correlated with mRNA expression (Pearson r=-0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high-glucose CD 34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD 34+ stem cells "memorize" the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration

Território e territorialidade no contexto hospitalar: uma abordagem interdisciplinar

Este artigo trata o hospital como território de organização complexa, atravessado por múltiplos interesses, que ocupa lugar crítico na prestação de serviços de saúde, lugar de construção de identidades profissionais, com grande reconhecimento social. O objetivo diz respeito a compreender o hospital na perspectiva interdisciplinar. Para tanto, buscou-se o referencial teórico referente às concepções de território e territorialidade, oriundas da geografia e de outros campos do conhecimento, como a ciência da saúde e a filosofia. A partir da interação entre estas disciplinas aborda-se o hospital como território de produção de atos de saúde formado por segmentos e superfícies, agenciamentos entre profissionais e usuários que se entrecortam em um emaranhado de linhas de segmentaridade; nós, redes e malhas que revelam a produção territorial; poder e disciplinamento e o saber-poder que revelam as relações sociais, efetivadas entre os sujeitos e o objeto, ou seja, as relações que se concretizam no território e significam territorialidade. Concluiu-se, então, que o território hospitalar, como os demais territórios, é a expressão concreta e abstrata do espaço apropriado, produzido, formado em sua multidimensionalidade, pelos atores sociais que o (re)definem constantemente em suas cotidianidades, num campo de forças relacionalmente emaranhado por poderes nas mais variadas intensidades