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排序方式: 共有336条查询结果,搜索用时 11 毫秒
271.
This article details the development of a new area classification for Britain based on internal migration variables taken from the 2001 Census. An explanation of why general-purpose area classifications already in existence are not ideal for internal migration analysis is provided, before an account of the construction of the new classification is given. The latter involves justification of the choice of variables, explanation of the methodology adopted and presentation of the final typology. 相似文献
272.
Sohn RA Willis C Humphris S Shank TM Singh H Edmonds HN Kunz C Hedman U Helmke E Jakuba M Liljebladh B Linder J Murphy C Nakamura K Sato T Schlindwein V Stranne C Tausenfreund M Upchurch L Winsor P Jakobsson M Soule A 《Nature》2008,453(7199):1236-1238
Roughly 60% of the Earth's outer surface is composed of oceanic crust formed by volcanic processes at mid-ocean ridges. Although only a small fraction of this vast volcanic terrain has been visually surveyed or sampled, the available evidence suggests that explosive eruptions are rare on mid-ocean ridges, particularly at depths below the critical point for seawater (3,000 m). A pyroclastic deposit has never been observed on the sea floor below 3,000 m, presumably because the volatile content of mid-ocean-ridge basalts is generally too low to produce the gas fractions required for fragmenting a magma at such high hydrostatic pressure. We employed new deep submergence technologies during an International Polar Year expedition to the Gakkel ridge in the Arctic Basin at 85 degrees E, to acquire photographic and video images of 'zero-age' volcanic terrain on this remote, ice-covered ridge. Here we present images revealing that the axial valley at 4,000 m water depth is blanketed with unconsolidated pyroclastic deposits, including bubble wall fragments (limu o Pele), covering a large (>10 km(2)) area. At least 13.5 wt% CO(2) is necessary to fragment magma at these depths, which is about tenfold the highest values previously measured in a mid-ocean-ridge basalt. These observations raise important questions about the accumulation and discharge of magmatic volatiles at ultraslow spreading rates on the Gakkel ridge and demonstrate that large-scale pyroclastic activity is possible along even the deepest portions of the global mid-ocean ridge volcanic system. 相似文献
273.
Garnett MJ Edelman EJ Heidorn SJ Greenman CD Dastur A Lau KW Greninger P Thompson IR Luo X Soares J Liu Q Iorio F Surdez D Chen L Milano RJ Bignell GR Tam AT Davies H Stevenson JA Barthorpe S Lutz SR Kogera F Lawrence K McLaren-Douglas A Mitropoulos X Mironenko T Thi H Richardson L Zhou W Jewitt F Zhang T O'Brien P Boisvert JL Price S Hur W Yang W Deng X Butler A Choi HG Chang JW Baselga J Stamenkovic I Engelman JA Sharma SV Delattre O Saez-Rodriguez J Gray NS Settleman J Futreal PA Haber DA 《Nature》2012,483(7391):570-575
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. 相似文献
274.
Kang K Panzano VC Chang EC Ni L Dainis AM Jenkins AM Regna K Muskavitch MA Garrity PA 《Nature》2012,481(7379):76-80
Discriminating among sensory stimuli is critical for animal survival. This discrimination is particularly essential when evaluating whether a stimulus is noxious or innocuous. From insects to humans, transient receptor potential (TRP) channels are key transducers of thermal, chemical and other sensory cues. Many TRPs are multimodal receptors that respond to diverse stimuli, but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. Although Drosophila TRPA1 responds to both noxious chemicals and innocuous warming, we find that TRPA1-expressing chemosensory neurons respond to chemicals but not warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with reduced thermosensitivity compared to the previously described isoform. At the molecular level, this reduction results from a unique region that robustly reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity is critical: when the thermosensory isoform is expressed in chemosensors, flies respond to innocuous warming with regurgitation, a nocifensive response. TRPA1 isoform diversity is conserved in malaria mosquitoes, indicating that similar mechanisms may allow discrimination of host-derived warmth--an attractant--from chemical repellents. These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive. 相似文献
275.
H Pälike MW Lyle H Nishi I Raffi A Ridgwell K Gamage A Klaus G Acton L Anderson J Backman J Baldauf C Beltran SM Bohaty P Bown W Busch JE Channell CO Chun M Delaney P Dewangan T Dunkley Jones KM Edgar H Evans P Fitch GL Foster N Gussone H Hasegawa EC Hathorne H Hayashi JO Herrle A Holbourn S Hovan K Hyeong K Iijima T Ito S Kamikuri K Kimoto J Kuroda L Leon-Rodriguez A Malinverno TC Moore BH Murphy DP Murphy H Nakamura K Ogane C Ohneiser C Richter R Robinson EJ Rohling O Romero K Sawada H Scher 《Nature》2012,488(7413):609-614
Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth. 相似文献
276.
Eisenbarth SC Williams A Colegio OR Meng H Strowig T Rongvaux A Henao-Mejia J Thaiss CA Joly S Gonzalez DG Xu L Zenewicz LA Haberman AM Elinav E Kleinstein SH Sutterwala FS Flavell RA 《Nature》2012,484(7395):510-513
NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10(-/-) mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and -independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4(+) T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs. 相似文献
277.
Approaching a state shift in Earth's biosphere 总被引:1,自引:0,他引:1
Barnosky AD Hadly EA Bascompte J Berlow EL Brown JH Fortelius M Getz WM Harte J Hastings A Marquet PA Martinez ND Mooers A Roopnarine P Vermeij G Williams JW Gillespie R Kitzes J Marshall C Matzke N Mindell DP Revilla E Smith AB 《Nature》2012,486(7401):52-58
Localized ecological systems are known to shift abruptly and irreversibly from one state to another when they are forced across critical thresholds. Here we review evidence that the global ecosystem as a whole can react in the same way and is approaching a planetary-scale critical transition as a result of human influence. The plausibility of a planetary-scale 'tipping point' highlights the need to improve biological forecasting by detecting early warning signs of critical transitions on global as well as local scales, and by detecting feedbacks that promote such transitions. It is also necessary to address root causes of how humans are forcing biological changes. 相似文献
278.
279.
Barouch DH Liu J Li H Maxfield LF Abbink P Lynch DM Iampietro MJ SanMiguel A Seaman MS Ferrari G Forthal DN Ourmanov I Hirsch VM Carville A Mansfield KG Stablein D Pau MG Schuitemaker H Sadoff JC Billings EA Rao M Robb ML Kim JH Marovich MA Goudsmit J Michael NL 《Nature》2012,482(7383):89-93
Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys. 相似文献
280.
Potential impacts of a warming climate on water availability in snow-dominated regions 总被引:25,自引:0,他引:25
All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate--for example, on the frequency of heatwaves--this increase in surface temperatures has important consequences for the hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. In a warmer world, less winter precipitation falls as snow and the melting of winter snow occurs earlier in spring. Even without any changes in precipitation intensity, both of these effects lead to a shift in peak river runoff to winter and early spring, away from summer and autumn when demand is highest. Where storage capacities are not sufficient, much of the winter runoff will immediately be lost to the oceans. With more than one-sixth of the Earth's population relying on glaciers and seasonal snow packs for their water supply, the consequences of these hydrological changes for future water availability--predicted with high confidence and already diagnosed in some regions--are likely to be severe. 相似文献