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251.
Ibrahim M.AL-HARKAN 《系统科学与系统工程学报(英文版)》2005,14(2):187-206
1.Introduction Production sequencing and scheduling is one of the most important activities in production planning and control.Sequencing is defined as the order in which the jobs are processed through the machines.The allocation of machines over time to process a collection of jobs is defined as Scheduling.Several methods have been developed to solve the scheduling problem which can be classified as follows:1)efficient optimal methods,2)implicit and explicit,or complete enumerative methods,a… 相似文献
252.
253.
Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. 总被引:36,自引:0,他引:36
A Brazma P Hingamp J Quackenbush G Sherlock P Spellman C Stoeckert J Aach W Ansorge C A Ball H C Causton T Gaasterland P Glenisson F C Holstege I F Kim V Markowitz J C Matese H Parkinson A Robinson U Sarkans S Schulze-Kremer J Stewart R Taylor J Vilo M Vingron 《Nature genetics》2001,29(4):365-371
Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it. 相似文献
254.
Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency 总被引:13,自引:0,他引:13
Irwin WA Bergamin N Sabatelli P Reggiani C Megighian A Merlini L Braghetta P Columbaro M Volpin D Bressan GM Bernardi P Bonaldo P 《Nature genetics》2003,35(4):367-371
Collagen VI is an extracellular matrix protein that forms a microfilamentous network in skeletal muscles and other organs. Inherited mutations in genes encoding collagen VI in humans cause two muscle diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy. We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy. The pathophysiological defects and mechanisms leading to the myopathic disorder were not known. Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis. We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis. These defects were reversible, as they could be normalized by plating Col6a1-/- myofibers on collagen VI or by addition of cyclosporin A (CsA), the inhibitor of mitochondrial permeability transition pore (PTP). Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo. These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention. 相似文献
255.
Chiang C Jacobsen JC Ernst C Hanscom C Heilbut A Blumenthal I Mills RE Kirby A Lindgren AM Rudiger SR McLaughlan CJ Bawden CS Reid SJ Faull RL Snell RG Hall IM Shen Y Ohsumi TK Borowsky ML Daly MJ Lee C Morton CC MacDonald ME Gusella JF Talkowski ME 《Nature genetics》2012,44(4):390-7, S1
We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. 相似文献
256.
Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes 总被引:56,自引:0,他引:56
Double-stranded RNA interference (RNAi) is an effective method for disrupting expression of specific genes in Caenorhabditis elegans and other organisms. Applications of this reverse-genetics tool, however, are somewhat restricted in nematodes because introduced dsRNA is not stably inherited. Another difficulty is that RNAi disruption of late-acting genes has been generally less consistent than that of embryonically expressed genes, perhaps because the concentration of dsRNA becomes lower as cellular division proceeds or as developmental time advances. In particular, some neuronally expressed genes appear refractory to dsRNA-mediated interference. We sought to extend the applicability of RNAi by in vivo expression of heritable inverted-repeat (IR) genes. We assayed the efficacy of in vivo-driven RNAi in three situations for which heritable, inducible RNAi would be advantageous: (i) production of large numbers of animals deficient for gene activities required for viability or reproduction; (ii) generation of large populations of phenocopy mutants for biochemical analysis; and (iii) effective gene inactivation in the nervous system. We report that heritable IR genes confer potent and specific gene inactivation for each of these applications. We suggest that a similar strategy might be used to test for dsRNA interference effects in higher organisms in which it is feasible to construct transgenic animals, but impossible to directly or transiently introduce high concentrations of dsRNA. 相似文献
257.
Purification and cloning of amyloid precursor protein beta-secretase from human brain 总被引:40,自引:0,他引:40
Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D Zhao J McConlogue L John V 《Nature》1999,402(6761):537-540
Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase. 相似文献
258.
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. 总被引:226,自引:0,他引:226
L A Donehower M Harvey B L Slagle M J McArthur C A Montgomery J S Butel A Bradley 《Nature》1992,356(6366):215-221
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours. 相似文献
259.
A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. 总被引:46,自引:0,他引:46
P Basset J P Bellocq C Wolf I Stoll P Hutin J M Limacher O L Podhajcer M P Chenard M C Rio P Chambon 《Nature》1990,348(6303):699-704
A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies. 相似文献
260.
Two experiments have been carried out to verify the effect of ethylene on the primary attraction ofPhloeotribus scarabaeoides under both laboratory and field conditions. The experiments were based on the enhancement of ethylene production by olive branches and trunks after the application of (2-chloroethyl)phosphonic acid. Under laboratory conditions, the beetles' response was strongly stimulated on the treated branches. Under field conditions, the treatment aided the location of the olive wood by the flying beetles, and the attack density was significantly greater in the treated wood at the end of the experiment. 相似文献