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51.
Kidney graft survival and matching for HL-A and ABO antigens 总被引:3,自引:0,他引:3
52.
Changing Arctic Ocean freshwater pathways 总被引:7,自引:0,他引:7
Freshening in the Canada basin of the Arctic Ocean began in the 1990s and continued to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly of the 1970s, raising the spectre of slowing global ocean circulation. Freshening has been attributed to increased sea ice melting and contributions from runoff, but a leading explanation has been a strengthening of the Beaufort High--a characteristic peak in sea level atmospheric pressure--which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation. 相似文献
53.
R Straussman T Morikawa K Shee M Barzily-Rokni ZR Qian J Du A Davis MM Mongare J Gould DT Frederick ZA Cooper PB Chapman DB Solit A Ribas RS Lo KT Flaherty S Ogino JA Wargo TR Golub 《Nature》2012,487(7408):500-504
Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance. 相似文献
54.
The DNA polymerase V (pol V) and RecA proteins are essential components of a mutagenic translesion synthesis pathway in Escherichia coli designed to cope with DNA damage. Previously, it has been assumed that RecA binds to the DNA template strand being copied. Here we show, however, that pol-V-catalysed translesion synthesis, in the presence or absence of the beta-processivity-clamp, occurs only when RecA nucleoprotein filaments assemble or RecA protomers bind on separate single-stranded (ss)DNA molecules in trans. A 3'-proximal RecA filament end on trans DNA is essential for stimulation; however, synthesis is strengthened by further pol V-RecA interactions occurring elsewhere along a trans nucleoprotein filament. We suggest that trans-stimulation of pol V by RecA bound to ssDNA reflects a distinctive regulatory mechanism of mutation that resolves the paradox of RecA filaments assembled in cis on a damaged template strand obstructing translesion DNA synthesis despite the absolute requirement of RecA for SOS mutagenesis. 相似文献
55.
56.
Great Himalayan earthquakes and the Tibetan plateau 总被引:7,自引:0,他引:7
It has been assumed that Himalayan earthquakes are driven by the release of compressional strain accumulating close to the Greater Himalaya. However, elastic models of the Indo-Asian collision using recently imaged subsurface interface geometries suggest that a substantial fraction of the southernmost 500 kilometres of the Tibetan plateau participates in driving great ruptures. We show here that this Tibetan reservoir of elastic strain energy is drained in proportion to Himalayan rupture length, and that the consequent growth of slip and magnitude with rupture area, when compared to data from recent earthquakes, can be used to infer a approximately 500-year renewal time for these events. The elastic models also illuminate two puzzling features of plate boundary seismicity: how great earthquakes can re-rupture regions that have already ruptured in recent smaller earthquakes and how mega-earthquakes with greater than 20 metres slip may occur at millennia-long intervals, driven by residual strain following many centuries of smaller earthquakes. 相似文献
57.
1. Introduction In his famous seminal book (Rogers 1962), Rogers introduced and popularized a generic framework for analyzing and describing how the mechanism of diffusion of innovations works inside a given population. In this general approach, “innovation” can of course be understood in a large way: it may indeed referto various contexts such as the learning of a new practice, the use of a new tool, the launch of a new product, etc. The strength of Rogers' point of view comes from the fac… 相似文献
58.
59.
This paper generalizes the method of Ngô and Winkler (2010, 2011) for finding rational general solutions of a first order non-autonomous algebraic ordinary differential equation (AODE) to the case of a higher order AODE, provided a proper parametrization of its solution hypersurface. The authors reduce the problem of finding the rational general solution of a higher order AODE to finding the rational general solution of an associated system. The rational general solutions of the original AODE and its associated system are in computable 1-1 correspondence. The authors give necessary and sufficient conditions for the associated system to have a rational solution based on proper reparametrization of invariant algebraic space curves. The authors also relate invariant space curves to first integrals and characterize rationally solvable systems by rational first integrals. 相似文献
60.
Why fishing magnifies fluctuations in fish abundance 总被引:1,自引:0,他引:1
Anderson CN Hsieh CH Sandin SA Hewitt R Hollowed A Beddington J May RM Sugihara G 《Nature》2008,452(7189):835-839
It is now clear that fished populations can fluctuate more than unharvested stocks. However, it is not clear why. Here we distinguish among three major competing mechanisms for this phenomenon, by using the 50-year California Cooperative Oceanic Fisheries Investigations (CalCOFI) larval fish record. First, variable fishing pressure directly increases variability in exploited populations. Second, commercial fishing can decrease the average body size and age of a stock, causing the truncated population to track environmental fluctuations directly. Third, age-truncated or juvenescent populations have increasingly unstable population dynamics because of changing demographic parameters such as intrinsic growth rates. We find no evidence for the first hypothesis, limited evidence for the second and strong evidence for the third. Therefore, in California Current fisheries, increased temporal variability in the population does not arise from variable exploitation, nor does it reflect direct environmental tracking. More fundamentally, it arises from increased instability in dynamics. This finding has implications for resource management as an empirical example of how selective harvesting can alter the basic dynamics of exploited populations, and lead to unstable booms and busts that can precede systematic declines in stock levels. 相似文献