An improved branch-and-bound algorithm to minimize the weighted flowtime on identical parallel machines with family setup times

This article investigates identical parallel machines scheduling with family setup times. The objective function being the weighted sum of completion times, the problem is known to be strongly NP-hard. We propose a constructive heuristic algorithm and three complementary lower bounds. Two of these bounds proceed by elimination of setup times or by distributing each of them to jobs of the corresponding family, while the third one is based on a lagrangian relaxation. The bounds and the heuristic are incorporated into a branch-and-bound algorithm. Experimental results obtained outperform those of the methods presented in previous works, in term of size of solved problems.     

Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation

Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation.     

Expression and functional characterization of artificial mutants of interleukin-2 receptor

The physiological proliferation of T lymphocytes (T cells) requires interaction between the humoral growth factor, interleukin 2 (IL-2) and its cell-surface receptor. Studies of IL-2 binding to the IL-2 receptor (IL-2R) on T cells have revealed that there are two distinct species of IL-2R, one with high and one with low affinity. Isolation and characterization of cDNA for the human IL-2R made it possible to deduce the complete primary sequence (251 residues) of the receptor protein. However, expression of IL-2R alone is not sufficient for either growth signal transduction or high-affinity site formation: another lymphocyte-specific molecule called converter seems to be required for the biological activity of IL-2R. We found that the converter did not form a stable complex with IL-2R unless the receptor bound the ligand (the 'affinity conversion' model). To discover which are the functionally important parts of the human IL-2R we have constructed artificial mutant cDNAs encoding the receptor. The mutant receptors produced from them had deletions or substitutions in the cytoplasmic region (13 residues), the transmembrane region (19 residues) or the carboxy-terminal portion of the extracellular region (219 residues). All were active in growth signal transduction, efficient internalization and high-affinity site formation in two mouse T-cell lines, suggesting that the extracellular region of IL-2R and the converter may be responsible for growth signal transduction.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin

Summary I.v. botulinum toxin after 60–90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.Acknowledgment. We are grateful to the generosity of Dr Edward J. Schantz, Food Research Institute, University of Wisconsin, for the botulinum toxin used. — This research was supported by NIH grant 1 RO1 AM 17125, The Secretion of Pepsin.     

Ultrahigh-quality silicon carbide single crystals

Silicon carbide (SiC) has a range of useful physical, mechanical and electronic properties that make it a promising material for next-generation electronic devices. Careful consideration of the thermal conditions in which SiC [0001] is grown has resulted in improvements in crystal diameter and quality: the quantity of macroscopic defects such as hollow core dislocations (micropipes), inclusions, small-angle boundaries and long-range lattice warp has been reduced. But some macroscopic defects (about 1-10 cm(-2)) and a large density of elementary dislocations (approximately 10(4) cm(-2)), such as edge, basal plane and screw dislocations, remain within the crystal, and have so far prevented the realization of high-efficiency, reliable electronic devices in SiC (refs 12-16). Here we report a method, inspired by the dislocation structure of SiC grown perpendicular to the c-axis (a-face growth), to reduce the number of dislocations in SiC single crystals by two to three orders of magnitude, rendering them virtually dislocation-free. These substrates will promote the development of high-power SiC devices and reduce energy losses of the resulting electrical systems.     

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.     

Species-specific differences in the mitogenic activity of heparin-binding growth factors in the sera of various mammals

Sera from different mammalian species displayed great differences in mitogenic activity, as measured by stimulation of DNA synthesis in BALB/c 3T3 cells (3T3 cells). Among the sera examined, fetal bovine serum was least active, and increasing activity was detected in calf serum, human serum, rat serum and mouse serum, in that order. Rat and mouse sera exhibited extremely high mitogenic activity with 3T3 cells, but when TIG-1 human fetal lung fibroblasts were used for the DNA assay instead, the activity levels of all of the sera were lower, and the differences between them were smaller. To determine the reasons for these differences, the heparin-binding growth factors in each serum were separated on a heparin affinity column. Five peaks of DNA-stimulating activity were obtained. Three of these were found in all sera examined, with both 3T3 cells and TIG-1 cells. Two other peaks were found only with 3T3 cells; one was peculiar to rat and mouse sera, with extremely high activity in the rat, and the other was specific to fetal serum. The dependence of the activity of these peaks on the cells used for the test was confirmed using normal rat lung fibroblasts and immortalized rat kidney cells. These findings adequately explain the species-specific differences in mitogenic activity of whole sera, and the variation in activity depending on the cells used for assay of DNA synthesis.     

Identification of a pre-hibernating state in myocardium from nonhibernating chipmunks

Summary During the hibermating season, the amplitude of the cardiac action potential plateau of nonhibernating chipmunks was reduced. Replacing external Ca by Sr inhibited the electromechanical responses of these preparations. Similar properties were observed in hibernating animal preparations, suggesting that changes in cardiac function are already triggered before hibernation begins.15 December 1986