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991.
Bentley DR Deloukas P Dunham A French L Gregory SG Humphray SJ Mungall AJ Ross MT Carter NP Dunham I Scott CE Ashcroft KJ Atkinson AL Aubin K Beare DM Bethel G Brady N Brook JC Burford DC Burrill WD Burrows C Butler AP Carder C Catanese JJ Clee CM Clegg SM Cobley V Coffey AJ Cole CG Collins JE Conquer JS Cooper RA Culley KM Dawson E Dearden FL Durbin RM de Jong PJ Dhami PD Earthrowl ME Edwards CA Evans RS Gillson CJ Ghori J Green L Gwilliam R Halls KS Hammond S Harper GL Heathcott RW Holden JL 《Nature》2001,409(6822):942-943
We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones. 相似文献
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Kawai J Shinagawa A Shibata K Yoshino M Itoh M Ishii Y Arakawa T Hara A Fukunishi Y Konno H Adachi J Fukuda S Aizawa K Izawa M Nishi K Kiyosawa H Kondo S Yamanaka I Saito T Okazaki Y Gojobori T Bono H Kasukawa T Saito R Kadota K Matsuda H Ashburner M Batalov S Casavant T Fleischmann W Gaasterland T Gissi C King B Kochiwa H Kuehl P Lewis S Matsuo Y Nikaido I Pesole G Quackenbush J Schriml LM Staubli F Suzuki R Tomita M Wagner L Washio T Sakai K Okido T Furuno M Aono H Baldarelli R Barsh G 《Nature》2001,409(6821):685-690
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. 相似文献
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微重力条件下气/液两相流压降实验研究 总被引:4,自引:0,他引:4
利用俄罗斯IL-76失重飞机对微重力条件下方形截面管道内的水/气两相流压降进行了实验研究.利用本次微重力气/液两相流压降实验结果对一些目前常用的基于地面常重力实验结果的两相流压降预测模型(均相模型、Lockhart-Martinelli—Chisholm模型和Friedel模型)在微重力条件下的适用性进行了评估.比较发现,均相模型和Lockhart-Martinelli—Chisholm模型预测结果和实验数据差异很大;而Friedel模型的预测结果尽管也与实验数据有着明显的差别,但在这些模型中是误差最小的.因此,可以利用Friedel模型来对微重力气/液两相流压降进行初步预估,而新的、更精确的模型将依赖于更有物理意义的分析方法及不同重力条件下气/液两相流压降实验的结果. 相似文献
999.
Antibody neutralization and escape by HIV-1 总被引:62,自引:0,他引:62
Wei X Decker JM Wang S Hui H Kappes JC Wu X Salazar-Gonzalez JF Salazar MG Kilby JM Saag MS Komarova NL Nowak MA Hahn BH Kwong PD Shaw GM 《Nature》2003,422(6929):307-312
Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire. 相似文献
1000.
Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles. 相似文献