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101.
Buetow KH 《Science (New York, N.Y.)》2005,308(5723):821-824
Biomedicine has experienced explosive growth, fueled in parts by the substantial increase of government support, continued development of the biotechnology industry, and the increasing adoption of molecular-based medicine. At its core, it is composed of fiercely independent, innovative, entrepreneurial individuals, organizations, and institutions. The field has developed unprecedented capacity to characterize biologic systems at their most fundamental levels with the use of tools and technologies almost unimaginable a generation ago. Biomedicine is at the precipice of unlocking the very essence of biologic life and enabling a new generation of medicine. Development and deployment of cyberinfrastructure may prove to be on the critical path to obtaining these goals. 相似文献
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Romanowsky AJ Douglas NG Arnaboldi M Kuijken K Merrifield MR Napolitano NR Capaccioli M Freeman KC 《Science (New York, N.Y.)》2003,301(5640):1696-1698
The kinematics of the outer parts of three intermediate-luminosity elliptical galaxies were studied with the Planetary Nebula Spectrograph. The galaxies' velocity-dispersion profiles were found to decline with the radius, and dynamical modeling of the data indicates the presence of little if any dark matter in these galaxies' halos. This unexpected result conflicts with findings in other galaxy types and poses a challenge to current galaxy formation theories. 相似文献
104.
Wang Dechun Prato Tony Qiu Zeyuan Kitchen Newell R. Sudduth Kenneth A. 《Precision Agriculture》2003,4(1):35-52
Variable Rate Technology (VRT) has the potential to increase crop yields and improve water quality relative to Uniform Rate Technology (URT). The effects on profitability and water quality of adopting VRT for nitrogen (N) and lime were evaluated for corn production on four claypan soil fields in north central Missouri under average to better than average weather conditions. Variable N and lime rates were based on measured topsoil depth and soil pH, respectively. VRT rates were compared to two different uniform N applications (URT-Nl based on the topsoil depth within these claypan soil fields, and URT-N2 based on a typical N rate for corn production in this area). Expected corn yield was predicted based on topsoil depth, soil pH, N rate, and lime rate. Water quality benefits of VRT relative to URT were evaluated based on potential leachable N. Sensitivity analyses were performed using simulated topsoil data for topsoil depth and soil pH. Results showed that VRT was more profitable than URT in the four sample fields under URT-N1, and in two of the four fields under URT-N2. Greater variation in topsoil depth and soil pH resulted in higher profitability and greater water quality benefits with VRT. Results support adoption of VRT for N and lime application for other claypan soil fields with characteristics similar to those in the fields used in this study. 相似文献
105.
Wang Z Shen D Parsons DW Bardelli A Sager J Szabo S Ptak J Silliman N Peters BA van der Heijden MS Parmigiani G Yan H Wang TL Riggins G Powell SM Willson JK Markowitz S Kinzler KW Vogelstein B Velculescu VE 《Science (New York, N.Y.)》2004,304(5674):1164-1166
Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention. 相似文献
106.
Silva JM Marran K Parker JS Silva J Golding M Schlabach MR Elledge SJ Hannon GJ Chang K 《Science (New York, N.Y.)》2008,319(5863):617-620
By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy for screening short hairpin RNA (shRNA) collections for stable loss-of-function phenotypes. We assayed from 6000 to 20,000 shRNAs simultaneously to identify genes important for the proliferation and survival of five cell lines derived from human mammary tissue. Lethal shRNAs common to these cell lines targeted many known cell-cycle regulatory networks. Cell line-specific sensitivities to suppression of protein complexes and biological pathways also emerged, and these could be validated by RNA interference (RNAi) and pharmacologically. These studies establish a practical platform for genome-scale screening of complex phenotypes in mammalian cells and demonstrate that RNAi can be used to expose genotype-specific sensitivities. 相似文献
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109.
Abelson JF Kwan KY O'Roak BJ Baek DY Stillman AA Morgan TM Mathews CA Pauls DL Rasin MR Gunel M Davis NR Ercan-Sencicek AG Guez DH Spertus JA Leckman JF Dure LS Kurlan R Singer HS Gilbert DL Farhi A Louvi A Lifton RP Sestan N State MW 《Science (New York, N.Y.)》2005,310(5746):317-320
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS. 相似文献
110.
A mule cloned from fetal cells by nuclear transfer 总被引:1,自引:0,他引:1
Woods GL White KL Vanderwall DK Li GP Aston KI Bunch TD Meerdo LN Pate BJ 《Science (New York, N.Y.)》2003,301(5636):1063