A Revised ant colony system approach to vehicle routing problems /

Vehicle routing problems have various extensions such as time windows, multiple vehicles, backhauls, simultaneous delivery and pick-up, etc. The objectives of all these problems are to design optimal routes minimizing total distance traveled, minimizing number of vehicles, etc that satisfy corresponding constraints. In this study, an ant colony optimization based heuristic that can be used to solve various vehicle routing problems is proposed. The objective function considered to minimize the total distance traveled by all vehicles. The heuristic is applied to vehicle routing problem with time windows and vehicle routing with simultaneous delivery and pick-up. Vehicles are identical and capacities of the vehicles are finite. The time window constraints in the first problem are assumed to be strict. The proposed heuristic consists of four steps. First, a candidate list is formed for each customer in order to reduce computational time. Second, a feasible solution is found, and initial pheromone trails on each arc is calculated using it. Then, routes are constructed based on Dorigo et al. (1997). While visibility is calculated during route construction process, the distance between two customers, customers' distance to the depot and the time window associated with the customer to whom the ant is considered to move are considered. Pheromone trails are modified by both local and global pheromone update. Finally, constructed routes are improved using 2-opt algorithm. The algorithm have been tested on the benchmark problem instances of Solomon (1987) for vehicle routing problem with time windows, and benchmark problem instances of Min (1989) and Dethloff (2001) for vehicle routing with simultaneous delivery and pick-up. The algorithm is proven to give good results when compared to the best known results in the literature

Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model

Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor, which induced apoptosis through the mitochondrial pathway, independently from BCL2 in B16F10 cells and B16F10 injected C57BL6 allografts. </p

An observational, prospective, multicenter study on rescue high-frequency oscillatory ventilation in neonates failing with conventional ventilation

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