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101.
Harter AV  Gardner KA  Falush D  Lentz DL  Bye RA  Rieseberg LH 《Nature》2004,430(6996):201-205
Eastern North America is one of at least six regions of the world where agriculture is thought to have arisen wholly independently. The primary evidence for this hypothesis derives from morphological changes in the archaeobotanical record of three important crops--squash, goosefoot and sunflower--as well as an extinct minor cultigen, sumpweed. However, the geographical origins of two of the three primary domesticates--squash and goosefoot--are now debated, and until recently sunflower (Helianthus annuus L.) has been considered the only undisputed eastern North American domesticate. The discovery of 4,000-year-old domesticated sunflower remains from San Andrés, Tabasco, implies an earlier and possibly independent origin of domestication in Mexico and has stimulated a re-examination of the geographical origin of domesticated sunflower. Here we describe the genetic relationships and pattern of genetic drift between extant domesticated strains and wild populations collected from throughout the USA and Mexico. We show that extant domesticates arose in eastern North America, with a substantial genetic bottleneck occurring during domestication.  相似文献   
102.
Stuber N  Forster P  Rädel G  Shine K 《Nature》2006,441(7095):864-867
Air traffic condensation trails, or contrails, are believed to have a net atmospheric warming effect, although one that is currently small compared to that induced by other sources of human emissions. However, the comparably large growth rate of air traffic requires an improved understanding of the resulting impact of aircraft radiative forcing on climate. Contrails have an effect on the Earth's energy balance similar to that of high thin ice clouds. Their trapping of outgoing longwave radiation emitted by the Earth and atmosphere (positive radiative forcing) is partly compensated by their reflection of incoming solar radiation (negative radiative forcing). On average, the longwave effect dominates and the net contrail radiative forcing is believed to be positive. Over daily and annual timescales, varying levels of air traffic, meteorological conditions, and solar insolation influence the net forcing effect of contrails. Here we determine the factors most important for contrail climate forcing using a sophisticated radiative transfer model for a site in southeast England, located in the entrance to the North Atlantic flight corridor. We find that night-time flights during winter (December to February) are responsible for most of the contrail radiative forcing. Night flights account for only 25 per cent of daily air traffic, but contribute 60 to 80 per cent of the contrail forcing. Further, winter flights account for only 22 per cent of annual air traffic, but contribute half of the annual mean forcing. These results suggest that flight rescheduling could help to minimize the climate impact of aviation.  相似文献   
103.
An option prioritization technique is developed to efficiently elicit the preferences, both unknown and crisp, of decision makers (DMs) in strategic conflicts. In the Graph Model for Conflict Resolution, each DM has one or more options, each of which may be selected or not. A state, or possible scenario, is formed when all DMs make an option selection. The software GMCR II contains an option prioritization procedure that makes it easy for a modeller to enter a DM’s crisp preference ordering over the states using prioritized statements describing the DM’s preferred option combinations. This procedure is extended by adding two new logical connectives that describe uncertainty of preference. For each DM, a range of possible scores for each feasible state can then be calculated, facilitating the determination of a preference ordering containing uncertainty by comparing and ranking scores. To demonstrate how this new methodology can be used to represent unknown preferences in a real-world decision problem, it is applied to a Canadian dispute over proposed water exports.  相似文献   
104.
Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed ~600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.  相似文献   
105.
Introduction Ionic liquids (ILs) are proving to be increasingly inter-esting fluids for application in soft-matter materialssystems from electrochemistry to energetic materialsand are also studied as potential solvents in separationprocesses[1-19]. Proper…  相似文献   
106.
107.
X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000?K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.  相似文献   
108.
Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer’s disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood–brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Recent studies have highlighted a new, unexpected role for peripheral monocytes and macrophages in restricting cerebral Aβ fibrils, and possibly soluble oligomers. In AD transgenic (ADtg) mice, monocyte ablation or inhibition of their migration into the brain exacerbated Aβ pathology, while blood enrichment with monocytes and their increased recruitment to plaque lesion sites greatly diminished Aβ burden. Profound neuroprotective effects in ADtg mice were further achieved through increased cerebral recruitment of myelomonocytes overexpressing Aβ-degrading enzymes. This review summarizes the literature on cellular and molecular mechanisms of cerebral Aβ clearance with an emphasis on the role of peripheral monocytes and macrophages in Aβ removal.  相似文献   
109.
Secretogranin III (Scg3) is a member of the granin protein family that regulates the biogenesis of secretory granules. Scg3 was recently discovered as an angiogenic factor, expanding its functional role to extrinsic regulation. Unlike many other known angiogenic factors, the pro-angiogenic actions of Scg3 are restricted to pathological conditions. Among thousands of quantified endothelial ligands, Scg3 has the highest binding activity ratio to diabetic vs. healthy mouse retinas and lowest background binding to normal vessels. In contrast, vascular endothelial growth factor binds to and stimulates angiogenesis of both diabetic and control vasculature. Consistent with its role in pathological angiogenesis, Scg3-neutralizing antibodies alleviate retinal vascular leakage in mouse models of diabetic retinopathy and retinal neovascularization in oxygen-induced retinopathy mice. This review summarizes our current knowledge of Scg3 as a regulatory protein of secretory granules, highlights its new role as a highly disease-selective angiogenic factor, and envisions Scg3 inhibitors as “selective angiogenesis blockers” for targeted therapy.  相似文献   
110.
The hispid cotton rat ( Sigmodon hispidus ) has occurred in Nebraska for about 50 years and entered the state from the south via northward movements through Kansas. However, little is known about its status or distribution in the state in recent decades. We conducted surveys for S. hispidus in southern Nebraska at historical sites and sites without previous records to determine its current status. From 2004 to 2008, we documented cotton rats at 9 of 12 historical sites in south-central and extreme southeastern parts of the state, and we captured this species at 13 new sites in southwestern and south-central Nebraska. In the past 3 decades, the distribution of S. hispidus has expanded westward but not northward in the state. An explanation for such a shift is unclear. At this northern edge of its geographical range, pregnant females were captured from early April to early October, and nonreproductive females were captured from November to January. Males with enlarged testes occurred from late March to September. Aspects of its natural history in Nebraska are similar to those reported in Kansas.  相似文献   
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