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排序方式: 共有100条查询结果,搜索用时 765 毫秒
81.
Kishimoto M Antonucci R Blaes O Lawrence A Boisson C Albrecht M Leipski C 《Nature》2008,454(7203):492-494
Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model-an optically thick disk which is heated locally by the dissipation of gravitational binding energy-is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. 相似文献
82.
83.
M Krauthammer Y Kong BH Ha P Evans A Bacchiocchi JP McCusker E Cheng MJ Davis G Goh M Choi S Ariyan D Narayan K Dutton-Regester A Capatana EC Holman M Bosenberg M Sznol HM Kluger DE Brash DF Stern MA Materin RS Lo S Mane S Ma KK Kidd NK Hayward RP Lifton J Schlessinger TJ Boggon R Halaban 《Nature genetics》2012,44(9):1006-1014
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1(P29S)) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1(P29S) showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit. 相似文献
84.
Ellinor PT Lunetta KL Albert CM Glazer NL Ritchie MD Smith AV Arking DE Müller-Nurasyid M Krijthe BP Lubitz SA Bis JC Chung MK Dörr M Ozaki K Roberts JD Smith JG Pfeufer A Sinner MF Lohman K Ding J Smith NL Smith JD Rienstra M Rice KM Van Wagoner DR Magnani JW Wakili R Clauss S Rotter JI Steinbeck G Launer LJ Davies RW Borkovich M Harris TB Lin H Völker U Völzke H Milan DJ Hofman A Boerwinkle E Chen LY Soliman EZ Voight BF Li G Chakravarti A Kubo M Tedrow UB Rose LM Ridker PM Conen D Tsunoda T 《Nature genetics》2012,44(6):670-675
85.
Graubert TA Shen D Ding L Okeyo-Owuor T Lunn CL Shao J Krysiak K Harris CC Koboldt DC Larson DE McLellan MD Dooling DJ Abbott RM Fulton RS Schmidt H Kalicki-Veizer J O'Laughlin M Grillot M Baty J Heath S Frater JL Nasim T Link DC Tomasson MH Westervelt P DiPersio JF Mardis ER Ley TJ Wilson RK Walter MJ 《Nature genetics》2012,44(1):53-57
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis. 相似文献
86.
Bis JC Kavousi M Franceschini N Isaacs A Abecasis GR Schminke U Post WS Smith AV Cupples LA Markus HS Schmidt R Huffman JE Lehtimäki T Baumert J Münzel T Heckbert SR Dehghan A North K Oostra B Bevan S Stoegerer EM Hayward C Raitakari O Meisinger C Schillert A Sanna S Völzke H Cheng YC Thorsson B Fox CS Rice K Rivadeneira F Nambi V Halperin E Petrovic KE Peltonen L Wichmann HE Schnabel RB Dörr M Parsa A Aspelund T Demissie S Kathiresan S Reilly MP Taylor K Uitterlinden A Couper DJ Sitzer M 《Nature genetics》2011,43(10):940-947
Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events. 相似文献
87.
Wain LV Verwoert GC O'Reilly PF Shi G Johnson T Johnson AD Bochud M Rice KM Henneman P Smith AV Ehret GB Amin N Larson MG Mooser V Hadley D Dörr M Bis JC Aspelund T Esko T Janssens AC Zhao JH Heath S Laan M Fu J Pistis G Luan J Arora P Lucas G Pirastu N Pichler I Jackson AU Webster RJ Zhang F Peden JF Schmidt H Tanaka T Campbell H Igl W Milaneschi Y Hottenga JJ Vitart V Chasman DI Trompet S Bragg-Gresham JL Alizadeh BZ Chambers JC Guo X Lehtimäki T Kühnel B Lopez LM Polašek O Boban M Nelson CP 《Nature genetics》2011,43(10):1005-1011
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP. 相似文献
88.
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease 总被引:6,自引:0,他引:6
Buch S Schafmayer C Völzke H Becker C Franke A von Eller-Eberstein H Kluck C Bässmann I Brosch M Lammert F Miquel JF Nervi F Wittig M Rosskopf D Timm B Höll C Seeger M ElSharawy A Lu T Egberts J Fändrich F Fölsch UR Krawczak M Schreiber S Nürnberg P Tepel J Hampe J 《Nature genetics》2007,39(8):995-999
With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value P(CCA) = 4.1 x 10(-9)), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 x 10(-7)) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8-2.6, P = 1.4 x 10(-14)) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile. 相似文献
89.
90.
基于先验知识与模块性的网络社区结构探测算法 总被引:2,自引:0,他引:2
在分析模块性指标和Newman有关网络社区结构探测算法的基础上,提出了一种基于先验知识与模块性的社区结构探测算法.利用节点度等社会网络结构先验知识,获得一个社区结构的基本划分,然后进行社区的合并,以此获得一个清晰的社区结构.经计算机模拟网络、Ucinet软件网络和中国农民工社会网络的社区结构探测,结果表明所提算法比Newman的迭代次数减少近50%,并且可以获得更好的模块性指标. 相似文献