We have previously reported that serotonin (5-hydroxytryptamine [SHT]) alters cultured bovine pulmonary artery smooth muscle cell (SMC) configuration through two different regulatory mechanisms. We now report that 5HT also regulates SMC growth through these same two mechanisms-a stimulatory event initiated intracellularly and inhibition of growth resulting from a cell surface action. 5HT (1 ,M) plus 0.1 mM iproniazid (a 5HT metabolic inhibitor) produced a severalfold stimulation of DNA synthesis (as measured by ['H]thymidine incorporation) of SMCs after a 17-24-hour incubation with only a slight elevation of cellular cAMP. This stimulatory effect responded synergistically with other growth factors including plateletderived growth factor, fibroblast growth factor, and epidermal growth factor and was effectively reversed by 5HT uptake inhibition. It was not produced by 5-hydroxyindoleacetic acid, a metabolite of 5HT. In the presence of 1 pM 5HT plus 0.1 mM isobutylmethylxanthine (IBMX), cAMP was elevated eightfold, dendritic formation occurred, and ['H]thymidine labeling of SMCs was inhibited. Inhibition of labeling by ['H]thymidine was mimicked by other agents that elevated cellular cAMP (10 ,uM histamine, 1 ,M isoproterenol plus 0.1 mM IBMX, and 10 ,uM forskolin) and by 1 mM dibutyryl cAMP. This inhibitory effect was not blocked by either inhibition of 5HT uptake or 5HT-receptor antagonists ketanserin (5HT2); methiothepin, spiperone, and mianserin (5HT1/5HT2); and 3-tropanyl-indole-3-carboxylate and 3-tropanyl-3,5-dichlorobenzoate (5HT3). However, similar to 5HT, the 5HT,A agonist, (+)-8-hydroxy-(+)- We have previously found that 5HT causes a configurational change (dendritic formation) of bovine pulmonary artery SMCs in culture through actions at two different locations of the cell, one that requires 5HT uptake into the cell'5 and another that by guest on May 9, 2018
Recursion is a programming technique in which a solution can be expressed by a subroutine invoking itself either directly or indirectly. Many problems can be expressed simply using a recursive approach, however one of the drawbacks of using recursion is that it requires a stack, and often one does not know how much stack space is needed to obtain a recursive result. Stack overflow often results in spectacular failure with strange, often unrepeatable behaviour. Paraffin is a suite of generic units that can add parallelism to iterative and recursive problems. Some of the generics involve a load balancing technique described as "work-seeking". It was found that the recursive work seeking algorithm could be extended to also provide stack safety whereby the generics monitor the amount of remaining stack space and avoid stack overflow using a technique similar to load balancing. The stack safety feature also makes it attractive to consider Paraffin for use with code destined for execution on a single core. This paper describes how the recursive work-seeking algorithm was extended to provide the stack-safety feature, and then goes on to report some performance results using the generics.
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