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基于服务器/客户模式的的虚拟数控系统体系结构,讨论了虚拟数控系统的建模技术和基于VRML的实现方法,并指出虚拟数控机床的建模是虚拟数控加工过程仿真的实现关键.利用VRML语言、分布式对象技术和Java技术开发和建立了基于Web环境的虚拟数控系统原型。并对系统的开发平台进行了分析和介绍,同时给出了系统的运行实例.研究表明,所开发的系统是可行的和合理的. 相似文献
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Tumour evolution inferred by single-cell sequencing 总被引:1,自引:0,他引:1
Navin N Kendall J Troge J Andrews P Rodgers L McIndoo J Cook K Stepansky A Levy D Esposito D Muthuswamy L Krasnitz A McCombie WR Hicks J Wigler M 《Nature》2011,472(7341):90-94
Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates. 相似文献
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Dunham A Matthews LH Burton J Ashurst JL Howe KL Ashcroft KJ Beare DM Burford DC Hunt SE Griffiths-Jones S Jones MC Keenan SJ Oliver K Scott CE Ainscough R Almeida JP Ambrose KD Andrews DT Ashwell RI Babbage AK Bagguley CL Bailey J Bannerjee R Barlow KF Bates K Beasley H Bird CP Bray-Allen S Brown AJ Brown JY Burrill W Carder C Carter NP Chapman JC Clamp ME Clark SY Clarke G Clee CM Clegg SC Cobley V Collins JE Corby N Coville GJ Deloukas P Dhami P Dunham I Dunn M Earthrowl ME Ellington AG 《Nature》2004,428(6982):522-528
Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb. 相似文献
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Deloukas P Earthrowl ME Grafham DV Rubenfield M French L Steward CA Sims SK Jones MC Searle S Scott C Howe K Hunt SE Andrews TD Gilbert JG Swarbreck D Ashurst JL Taylor A Battles J Bird CP Ainscough R Almeida JP Ashwell RI Ambrose KD Babbage AK Bagguley CL Bailey J Banerjee R Bates K Beasley H Bray-Allen S Brown AJ Brown JY Burford DC Burrill W Burton J Cahill P Camire D Carter NP Chapman JC Clark SY Clarke G Clee CM Clegg S Corby N Coulson A Dhami P Dutta I Dunn M Faulkner L Frankish A 《Nature》2004,429(6990):375-381
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An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice 总被引:19,自引:0,他引:19
Roy CN Custodio AO de Graaf J Schneider S Akpan I Montross LK Sanchez M Gaudino A Hentze MW Andrews NC Muckenthaler MU 《Nature genetics》2004,36(5):481-485
Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp is part of the type II acute phase response and is thought to have a crucial regulatory role in sequestering iron in the context of ACD. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD. 相似文献
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The power function of basal metabolic rate scaling is expressed as aM(b), where a corresponds to a scaling constant (intercept), M is body mass, and b is the scaling exponent. The 3/4 power law (the best-fit b value for mammals) was developed from Kleiber's original analysis and, since then, most workers have searched for a single cause to explain the observed allometry. Here we present a multiple-causes model of allometry, where the exponent b is the sum of the influences of multiple contributors to metabolism and control. The relative strength of each contributor, with its own characteristic exponent value, is determined by the control contribution. To illustrate its use, we apply this model to maximum versus basal metabolic rates to explain the differing scaling behaviour of these two biological states in mammals. The main difference in scaling is that, for the basal metabolic rate, the O(2) delivery steps contribute almost nothing to the global b scaling exponent, whereas for the maximum metabolic rate, the O(2) delivery steps significantly increase the global b value. 相似文献
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Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis 总被引:21,自引:0,他引:21
Muckenthaler M Roy CN Custodio AO Miñana B deGraaf J Montross LK Andrews NC Hentze MW 《Nature genetics》2003,34(1):102-107
Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe-/-) or homozygous with respect to the orthologous 882G-->A mutation (Hfe(845A/845A)) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such as SLC11A2 (also called DMT1, DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-deficient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1. 相似文献
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