An important observation in supply chain management, known as the bullwhip effect, suggests that demand variability increases as one moves up a supply chain. In this paper we quantify this effect for simple, two-stage supply chains consisting of a single retailer and a single manufacturer. Our model includes two of the factors commonly assumed to cause the bullwhip effect: demand forecasting and order lead times. We extend these results to multiple-stage supply chains with and without centralized customer demand information and demonstrate that the bullwhip effect can be reduced, but not completely eliminated, by centralizing demand information.bullwhip effect, forecasting, information, inventory, lead time, supply chain, variability

Melanoma is a tumor of transformed melanocytes, which are derived from the embryonic neural crest. It is unknown to what extent the programs regulating neural crest development interact with mutations in the BRAF oncogene, the gene most commonly mutated in human melanoma1. We have utilized the zebrafish embryo to identify initiating transcriptional events upon BRAFV600E activation in the neural crest lineage. Transgenic mitf-BRAFV600E;p53-/- zebrafish embryos demonstrate a gene signature enriched for markers of multipotent neural crest cells, and exhibit a failure of terminal differentiation of neural crest progenitors. To determine if these early transcriptional events were important for melanoma pathogenesis, we performed a chemical genetic screen to identify small molecule suppressors of the neural crest lineage, which were then tested for effects in melanoma. One class of compounds, inhibitors of dihydroorotate dehydrogenase (DHODH) such as leflunomide, led to an almost complete abrogation of neural crest development in the zebrafish and a reduction in self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting transcriptional elongation of genes required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAFV600E oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have direct bearing upon subsequent melanoma formation.

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The electrochemical properties of the interfaces between an Sm 0.2 Ce 0.8 O 1.9 (samaria-doped ceria, SDC) electrolyte and porous composite cathodes consisting of Sm 0.5 Sr 0.5 CoO 3 (SSC) and SDC have been investigated in anode-supported single cells at low temperatures (400 -600 jC). The bilayer structures of the SDC electrolyte films (25 Am thick) and the NiO -SDC anode supports were formed by co-pressing and subsequent co-firing at 1350 jC for 5 h. The effect of composition, firing temperature, and microstructure of the composite cathodes on the electrochemical properties is systematically studied. Results indicate that the optimum firing temperature is about 950 jC, whereas the optimum content of SDC electrolyte in the composite cathodes is about 30 wt.%. It is noted that the addition of the proper amount of SDC to SSC dramatically improved the catalytic properties of the interfaces; reducing the interfacial resistance by more than one order of magnitude compared with an SSC cathode without SDC. D

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