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131.
Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases--pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators--caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues. 相似文献
132.
Ultracold atoms trapped by light offer robust quantum coherence and controllability, providing an attractive system for quantum information processing and for the simulation of complex problems in condensed matter physics. Many quantum information processing schemes require the manipulation and deterministic entanglement of individual qubits; this would typically be accomplished using controlled, state-dependent, coherent interactions among qubits. Recent experiments have made progress towards this goal by demonstrating entanglement among an ensemble of atoms confined in an optical lattice. Until now, however, there has been no demonstration of a key operation: controlled entanglement between atoms in isolated pairs. Here we use an optical lattice of double-well potentials to isolate and manipulate arrays of paired (87)Rb atoms, inducing controlled entangling interactions within each pair. Our experiment realizes proposals to use controlled exchange coupling in a system of neutral atoms. Although 87Rb atoms have nearly state-independent interactions, when we force two atoms into the same physical location, the wavefunction exchange symmetry of these identical bosons leads to state-dependent dynamics. We observe repeated interchange of spin between atoms occupying different vibrational levels, with a coherence time of more than ten milliseconds. This observation demonstrates the essential component of a neutral atom quantum SWAP gate (which interchanges the state of two qubits). Its 'half-implementation', the root SWAP gate, is entangling, and together with single-qubit rotations it forms a set of universal gates for quantum computation. 相似文献
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Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3 总被引:1,自引:0,他引:1
Oncogenic tyrosine kinases have proved to be promising targets for the development of highly effective anticancer drugs. However, tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (HER) family show only limited activity against HER2-driven breast cancers, despite effective inhibition of epidermal growth factor receptor (EGFR) and HER2 in vivo. The reasons for this are unclear. Signalling in trans is a key feature of this multimember family and the critically important phosphatidylinositol-3-OH kinase (PI(3)K)/Akt pathway is driven predominantly through transphosphorylation of the kinase-inactive HER3 (refs 9, 10). Here we show that HER3 and consequently PI(3)K/Akt signalling evade inhibition by current HER-family TKIs in vitro and in tumours in vivo. This is due to a compensatory shift in the HER3 phosphorylation-dephosphorylation equilibrium, driven by increased membrane HER3 expression driving the phosphorylation reaction and by reduced HER3 phosphatase activity impeding the dephosphorylation reaction. These compensatory changes are driven by Akt-mediated negative-feedback signalling. Although HER3 is not a direct target of TKIs, HER3 substrate resistance undermines their efficacy and has thus far gone undetected. The experimental abrogation of HER3 resistance by small interfering RNA knockdown restores potent pro-apoptotic activity to otherwise cytostatic HER TKIs, re-affirming the oncogene-addicted nature of HER2-driven tumours and the therapeutic promise of this oncoprotein target. However, because HER3 signalling is buffered against an incomplete inhibition of HER2 kinase, much more potent TKIs or combination strategies are required to silence oncogenic HER2 signalling effectively. The biologic marker with which to assess the efficacy of HER TKIs should be the transphosphorylation of HER3 rather than autophosphorylation. 相似文献
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Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer 总被引:1,自引:0,他引:1
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On Jupiter's moon Io, volcanic plumes and evaporating lava flows provide hot gases to form an atmosphere that is subsequently ionized. Some of Io's plasma is captured by the planet's strong magnetic field to form a co-rotating torus at Io's distance; the remaining ions and electrons form Io's ionosphere. The torus and ionosphere are also depleted by three time-variable processes that produce a banana-shaped cloud orbiting with Io, a giant nebula extending out to about 500 Jupiter radii, and a jet close to Io. No spatial constraints exist for the sources of the first two; they have been inferred only from modelling the patterns seen in the trace gas sodium observed far from Io. Here we report observations that reveal a spatially confined stream that ejects sodium only from the wake of the Io-torus interaction, together with a visually distinct, spherically symmetrical outflow region arising from atmospheric sputtering. The spatial extent of the ionospheric wake that feeds the stream is more than twice that observed by the Galileo spacecraft and modelled successfully. This implies considerable variability, and therefore the need for additional modelling of volcanically-driven, episodic states of the great jovian nebula. 相似文献