257 research outputs found

    Hybrid Meta-Heuristics for Robust Scheduling

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    The production and delivery of rapidly perishable goods in distributed supply networks involves a number of tightly coupled decision and optimization problems regarding the just-in-time production scheduling and the routing of the delivery vehicles in order to satisfy strict customer specified time-windows. Besides dealing with the typical combinatorial complexity related to activity assignment and synchronization, effective methods must also provide robust schedules, coping with the stochastic perturbations (typically transportation delays) affecting the distribution process. In this paper, we propose a novel metaheuristic approach for robust scheduling. Our approach integrates mathematical programming, multi-objective evolutionary computation, and problem-specific constructive heuristics. The optimization algorithm returns a set of solutions with different cost and risk tradeoffs, allowing the analyst to adapt the planning depending on the attitude to risk. The effectiveness of the approach is demonstrated by a real-world case concerning the production and distribution of ready-mixed concrete.Meta-Heuristics;Multi-Objective Genetic Optimization;Robust Scheduling;Supply Networks

    Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

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    AIMS: Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca2+ transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. MAIN METHODS: PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca2+-ATPase pump inhibitors. The role of Na+/Ca2+ exchanger was examined in experiments performed in zero Na+ medium. NO release and intracellular Ca2+ were measured through specific probes. KEY FINDINGS: In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca2+]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca2+ mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na+/Ca2+ exchanger and Ca2+-ATPase pump in restoring Ca2+ was found. SIGNIFICANCE: Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca2+ transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved
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