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Zaidi MR Davis S Noonan FP Graff-Cherry C Hawley TS Walker RL Feigenbaum L Fuchs E Lyakh L Young HA Hornyak TJ Arnheiter H Trinchieri G Meltzer PS De Fabo EC Merlino G 《Nature》2011,469(7331):548-553
Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients. 相似文献
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Bedding TR Mosser B Huber D Montalbán J Beck P Christensen-Dalsgaard J Elsworth YP García RA Miglio A Stello D White TR De Ridder J Hekker S Aerts C Barban C Belkacem K Broomhall AM Brown TM Buzasi DL Carrier F Chaplin WJ Di Mauro MP Dupret MA Frandsen S Gilliland RL Goupil MJ Jenkins JM Kallinger T Kawaler S Kjeldsen H Mathur S Noels A Aguirre VS Ventura P 《Nature》2011,471(7340):608-611
Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ~ 50 seconds) and those that are also burning helium (period spacing ~ 100 to 300 seconds). 相似文献
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Fault lubrication during earthquakes 总被引:8,自引:0,他引:8
Di Toro G Han R Hirose T De Paola N Nielsen S Mizoguchi K Ferri F Cocco M Shimamoto T 《Nature》2011,471(7339):494-498
The determination of rock friction at seismic slip rates (about 1?m?s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (~300) performed in rotary shear apparatus at slip rates of 0.1-2.6?m?s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15?km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved. 相似文献
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传递矩阵方法与矩形势垒的量子隧穿 总被引:2,自引:0,他引:2
利用传递矩阵方法精确计算了一维定态薛定谔方程,求解出电子穿过矩形势垒的透射系数,进一步研究了该透射系数与有效质量和矩形势垒参数的关系。数值计算结果表明,有效质量和矩形势垒参数对透射系数的影响同等重要。 相似文献
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在对钱家营矿原煤特性分析的基础上,利用选煤优化软件进行计算机优化,得出钱家营矿选煤厂重力分选最佳方案:各层煤单独分选出不同的精煤产品或采用选后配煤的方法将单独分选出的产品混合,以获得用户要求的产品.该方案比混合分选或混合后分级入选精煤产率高,可为选煤厂带来更好的经济效益. 相似文献