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Atomic force microscopy has been used to measure the surface profile of a periodic array of 10-nanometer (nm)-diameter holes fabricated by fast-atom beam milling of a smooth graphite surface in which a 3.5-nm-thick titanium oxide screen was used as a mask. The nanostructured titanium oxide mask was itself derived from a protein crystal template. Pattern transfer from the biological crystal to the metal oxide film and finally to the graphite substrate was accomplished entirely by parallel processing.  相似文献   
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Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.  相似文献   
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Six ice cores from Kilimanjaro provide an approximately 11.7-thousand-year record of Holocene climate and environmental variability for eastern equatorial Africa, including three periods of abrupt climate change: approximately 8.3, approximately 5.2, and approximately 4 thousand years ago (ka). The latter is coincident with the "First Dark Age," the period of the greatest historically recorded drought in tropical Africa. Variable deposition of F- and Na+ during the African Humid Period suggests rapidly fluctuating lake levels between approximately 11.7 and 4 ka. Over the 20th century, the areal extent of Kilimanjaro's ice fields has decreased approximately 80%, and if current climatological conditions persist, the remaining ice fields are likely to disappear between 2015 and 2020.  相似文献   
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TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis   总被引:1,自引:0,他引:1  
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.  相似文献   
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Rapid global warming of 5 degrees to 10 degrees C during the Paleocene-Eocene Thermal Maximum (PETM) coincided with major turnover in vertebrate faunas, but previous studies have found little floral change. Plant fossils discovered in Wyoming, United States, show that PETM floras were a mixture of native and migrant lineages and that plant range shifts were large and rapid (occurring within 10,000 years). Floral composition and leaf shape and size suggest that climate warmed by approximately 5 degrees C during the PETM and that precipitation was low early in the event and increased later. Floral response to warming and/or increased atmospheric CO2 during the PETM was comparable in rate and magnitude to that seen in postglacial floras and to the predicted effects of anthropogenic carbon release and climate change on future vegetation.  相似文献   
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Radio Doppler data from the Galileo spacecraft's encounter with Amalthea, one of Jupiter's small inner moons, on 5 November 2002 yield a mass of (2.08 +/- 0.15) x 10(18) kilograms. Images of Amalthea from two Voyager spacecraft in 1979 and Galileo imaging between November 1996 and June 1997 yield a volume of (2.43 +/- 0.22) x 10(6) cubic kilometers. The satellite thus has a density of 857 +/- 99 kilograms per cubic meter. We suggest that Amalthea is porous and composed of water ice, as well as rocky material, and thus formed in a cold region of the solar system, possibly not at its present location near Jupiter.  相似文献   
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A high-resolution crystallographic analysis of the nitrogenase MoFe-protein reveals a previously unrecognized ligand coordinated to six iron atoms in the center of the catalytically essential FeMo-cofactor. The electron density for this ligand is masked in structures with resolutions lower than 1.55 angstroms, owing to Fourier series termination ripples from the surrounding iron and sulfur atoms in the cofactor. The central atom completes an approximate tetrahedral coordination for the six iron atoms, instead of the trigonal coordination proposed on the basis of lower resolution structures. The crystallographic refinement at 1.16 angstrom resolution is consistent with this newly detected component being a light element, most plausibly nitrogen. The presence of a nitrogen atom in the cofactor would have important implications for the mechanism of dinitrogen reduction by nitrogenase.  相似文献   
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