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541.
Although the Moon currently has no internally generated magnetic field, palaeomagnetic data, combined with radiometric ages of Apollo samples, provide evidence for such a magnetic field from approximately 3.9 to 3.6 billion years (Gyr) ago, possibly owing to an ancient lunar dynamo. But the presence of a lunar dynamo during this time period is difficult to explain, because thermal evolution models for the Moon yield insufficient core heat flux to power a dynamo after approximately 4.2 Gyr ago. Here we show that a transient increase in core heat flux after an overturn of an initially stratified lunar mantle might explain the existence and timing of an early lunar dynamo. Using a three-dimensional spherical convection model, we show that a dense layer, enriched in radioactive elements (a 'thermal blanket'), at the base of the lunar mantle can initially prevent core cooling, thereby inhibiting core convection and magnetic field generation. Subsequent radioactive heating progressively increases the buoyancy of the thermal blanket, ultimately causing it to rise back into the mantle. The removal of the thermal blanket, proposed to explain the eruption of thorium- and titanium-rich lunar mare basalts, plausibly results in a core heat flux sufficient to power a short-lived lunar dynamo. 相似文献
542.
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab 总被引:40,自引:0,他引:40
HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies. 相似文献
543.
Single synaptic vesicles fusing transiently and successively without loss of identity 总被引:21,自引:0,他引:21
Vesicle fusion and recycling are particularly critical for ongoing neurotransmitter release in the small nerve terminals of the brain, which typically contain about 30 functional vesicles. However, the modes of exocytosis and endocytosis that operate at synapses of the central nervous system are incompletely understood. Here we show real-time visualization of a single vesicle fusing at a small synapse of the central nervous system, made possible by highly intensified charge-coupled device imaging of hippocampal synaptic terminals, in which a single vesicle was labelled with the fluorescent membrane marker FM1-43 (ref. 6). In a small number of cases, full loss of fluorescent membrane dye was elicited by a single action potential, consistent with classical complete collapse. In most cases, however, action potentials triggered only partial loss of fluorescence, suggesting vesicular retention of membrane marker, consistent with 'kiss-and-run' vesicle cycling. An alternative hypothesis of independent fusion of partially stained vesicles arising from endosomal splitting could be excluded by observations on the size and timing of successive fusion events. Thus, our experimental evidence supports a predominance of kiss-and-run fusion events and rapid vesicular re-use. 相似文献
544.
Neurons in the primary auditory cortex are tuned to the intensity and specific frequencies of sounds, but the synaptic mechanisms underlying this tuning remain uncertain. Inhibition seems to have a functional role in the formation of cortical receptive fields, because stimuli often suppress similar or neighbouring responses, and pharmacological blockade of inhibition broadens tuning curves. Here we use whole-cell recordings in vivo to disentangle the roles of excitatory and inhibitory activity in the tone-evoked responses of single neurons in the auditory cortex. The excitatory and inhibitory receptive fields cover almost exactly the same areas, in contrast to the predictions of classical lateral inhibition models. Thus, although inhibition is typically as strong as excitation, it is not necessary to establish tuning, even in the receptive field surround. However, inhibition and excitation occurred in a precise and stereotyped temporal sequence: an initial barrage of excitatory input was rapidly quenched by inhibition, truncating the spiking response within a few (1-4) milliseconds. Balanced inhibition might thus serve to increase the temporal precision and thereby reduce the randomness of cortical operation, rather than to increase noise as has been proposed previously. 相似文献
545.
The concept of quasiparticles in solid-state physics is an extremely powerful tool for describing complex many-body phenomena in terms of single-particle excitations. Introducing a simple particle, such as an electron, hole or phonon, deforms a many-body system through its interactions with other particles. In this way, the added particle is 'dressed' or 'renormalized' by a self-energy cloud that describes the response of the many-body system, so forming a new entity--the quasiparticle. Using ultrafast laser techniques, it is possible to impulsively generate bare particles and observe their subsequent dressing by the many-body interactions (that is, quasiparticle formation) on the time and energy scales governed by the Heisenberg uncertainty principle. Here we describe the coherent response of silicon to excitation with a 10-femtosecond (10(-14) s) laser pulse. The optical pulse interacts with the sample by way of the complex second-order nonlinear susceptibility to generate a force on the lattice driving coherent phonon excitation. Transforming the transient reflectivity signal into frequency-time space reveals interference effects leading to the coherent phonon generation and subsequent dressing of the phonon by electron-hole pair excitations. 相似文献
546.
Brüls T Gyapay G Petit JL Artiguenave F Vico V Qin S Tin-Wollam AM Da Silva C Muselet D Mavel D Pelletier E Levy M Fujiyama A Matsuda F Wilson R Rowen L Hood L Weissenbach J Saurin W Heilig R 《Nature》2001,409(6822):947-948
We report the construction of a tiling path of around 650 clones covering more than 99% of human chromosome 14. Clone overlap information to assemble the map was derived by comparing fully sequenced clones with a database of clone end sequences (sequence tag connector strategy). We selected homogeneously distributed seed points using an auxiliary high-resolution radiation hybrid map comprising 1,895 distinct positions. The high long-range continuity and low redundancy of the tiling path indicates that the sequence tag connector approach compares favourably with alternative mapping strategies. 相似文献
547.
548.
Miceli-Richard C Lesage S Rybojad M Prieur AM Manouvrier-Hanu S Häfner R Chamaillard M Zouali H Thomas G Hugot JP 《Nature genetics》2001,28(1):19-20
Lack of a maternal contribution to the genome at the imprinted domain on proximal chromosome 15 causes Angelman syndrome (AS) associated with neurobehavioral anomalies that include severe mental retardation, ataxia and epilepsy. Although AS patients have infrequent mutations in the gene encoding an E6-AP ubiquitin ligase required for long-term synaptic potentiation (LTP), most cases are attributed to de novo maternal deletions of 15q11-q13. We report here that a novel maternally expressed gene, ATP10C, maps within the most common interval of deletion and that ATP10C expression is virtually absent from AS patients with imprinting mutations, as well as from patients with maternal deletions of 15q11-q13. 相似文献
549.
550.