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131.
Michel JB Shen YK Aiden AP Veres A Gray MK;Google Books Team Pickett JP Hoiberg D Clancy D Norvig P Orwant J Pinker S Nowak MA Aiden EL 《Science (New York, N.Y.)》2011,331(6014):176-182
We constructed a corpus of digitized texts containing about 4% of all books ever printed. Analysis of this corpus enables us to investigate cultural trends quantitatively. We survey the vast terrain of 'culturomics,' focusing on linguistic and cultural phenomena that were reflected in the English language between 1800 and 2000. We show how this approach can provide insights about fields as diverse as lexicography, the evolution of grammar, collective memory, the adoption of technology, the pursuit of fame, censorship, and historical epidemiology. Culturomics extends the boundaries of rigorous quantitative inquiry to a wide array of new phenomena spanning the social sciences and the humanities. 相似文献
132.
Zhang Z Gildersleeve J Yang YY Xu R Loo JA Uryu S Wong CH Schultz PG 《Science (New York, N.Y.)》2004,303(5656):371-373
Posttranslational modifications of proteins regulate many biological processes, including metabolism, signal transduction, and gene expression. The synthetic challenges associated with generating homogeneous populations of selectively modified proteins, however, have hindered detailed studies of the effects of these modifications on protein structure and function. Here, we report an approach to the cotranslational synthesis of selectively glycosylated proteins in which the modified amino acid is genetically encoded. We show that myoglobin containing beta-N-acetylglucosamine (GlcNAc)-serine at a defined position can be expressed in Escherichia coli in good yield and with high fidelity. The beta-GlcNAc moiety can be recognized by a saccharide-binding protein, or subsequently modified with a galactosyltransferase to build more complex carbohydrates. This approach should be generally applicable to other posttranslational modifications such as protein phosphorylation, acetylation, and methylation. 相似文献
133.
Anatomy of a conformational change: hinged "lid" motion of the triosephosphate isomerase loop 总被引:14,自引:0,他引:14
Triosephosphate isomerase (TIM) is used as a model system for the study of how a localized conformational change in a protein structure is produced and related to enzyme reactivity. An 11-residue loop region moves more than 7 angstroms and closes over the active site when substrate binds. The loop acts like a "lid" in that it moves rigidly and is attached by two hinges to the remainder of the protein. The nature of the motion appears to be built into the loop by conserved residues; the hinge regions, in contrast, are not conserved. Results of molecular dynamics calculations confirm the structural analysis and suggest a possible ligand-induced mechanism for loop closure. 相似文献
134.
The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein-the approximately 450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations-substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes-played a major role in determining GR's evolutionary trajectory. 相似文献
135.
We present three-dimensional reconstructions of coronal mass ejections (CMEs), which were obtained through polarization analysis of single-view images recorded with the use of the Large Angle and Spectrometric Coronagraph (LASCO) C2 coronagraph on board the Solar and Heliospheric Observatory (SOHO) spacecraft. Analysis of a loop-like CME shows a complex three-dimensional structure centered at 40 degrees from the plane of the sky, moving radially at 250 kilometers/second. Reconstruction of two halo CMEs suggests that these events are expanding loop arcades. 相似文献
136.
137.
Dagdigian J 《Science (New York, N.Y.)》2003,302(5652):1893
138.
Morrow EM Yoo SY Flavell SW Kim TK Lin Y Hill RS Mukaddes NM Balkhy S Gascon G Hashmi A Al-Saad S Ware J Joseph RM Greenblatt R Gleason D Ertelt JA Apse KA Bodell A Partlow JN Barry B Yao H Markianos K Ferland RJ Greenberg ME Walsh CA 《Science (New York, N.Y.)》2008,321(5886):218-223
To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations. 相似文献
139.
Johnson WL Kaltenboeck G Demetriou MD Schramm JP Liu X Samwer K Kim CP Hofmann DC 《Science (New York, N.Y.)》2011,332(6031):828-833
The development of metal alloys that form glasses at modest cooling rates has stimulated broad scientific and technological interest. However, intervening crystallization of the liquid in even the most robust bulk metallic glass-formers is orders of magnitude faster than in many common polymers and silicate glass-forming liquids. Crystallization limits experimental studies of the undercooled liquid and hampers efforts to plastically process metallic glasses. We have developed a method to rapidly and uniformly heat a metallic glass at rates of 10(6) kelvin per second to temperatures spanning the undercooled liquid region. Liquid properties are subsequently measured on millisecond time scales at previously inaccessible temperatures under near-adiabatic conditions. Rapid thermoplastic forming of the undercooled liquid into complex net shapes is implemented under rheological conditions typically used in molding of plastics. By operating in the millisecond regime, we are able to "beat" the intervening crystallization and successfully process even marginal glass-forming alloys with very limited stability against crystallization that are not processable by conventional heating. 相似文献
140.
Junt T Schulze H Chen Z Massberg S Goerge T Krueger A Wagner DD Graf T Italiano JE Shivdasani RA von Andrian UH 《Science (New York, N.Y.)》2007,317(5845):1767-1770
Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis. 相似文献