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111.
During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.  相似文献   
112.
Galaxies had their most significant impact on the Universe when they assembled their first generations of stars. Energetic photons emitted by young, massive stars in primeval galaxies ionized the intergalactic medium surrounding their host galaxies, cleared sightlines along which the light of the young galaxies could escape, and fundamentally altered the physical state of the intergalactic gas in the Universe continuously until the present day. Observations of the cosmic microwave background, and of galaxies and quasars at the highest redshifts, suggest that the Universe was reionized through a complex process that was completed about a billion years after the Big Bang, by redshift z?≈?6. Detecting ionizing Lyman-α photons from increasingly distant galaxies places important constraints on the timing, location and nature of the sources responsible for reionization. Here we report the detection of Lyα photons emitted less than 600?million years after the Big Bang. UDFy-38135539 (ref. 5) is at a redshift of z = 8.5549?±?0.0002, which is greater than those of the previously known most distant objects, at z = 8.2 (refs 6 and 7) and z = 6.96 (ref. 8). We find that this single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby.  相似文献   
113.
Clarkson AN  Huang BS  Macisaac SE  Mody I  Carmichael ST 《Nature》2010,468(7321):305-309
Stroke is a leading cause of disability, but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage-the peri-infarct zone-is critical for rehabilitation, as it shows heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas. Thus, understanding the neuronal properties constraining this plasticity is important for the development of new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA(A) receptors and is caused by an impairment in GABA (γ-aminobutyric acid) transporter (GAT-3/GAT-4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for α5-subunit-containing extrasynaptic GABA(A) receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of α5- or δ-subunit-containing GABA(A) receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA(A) receptor function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.  相似文献   
114.
成品油管道低洼处积水引起的腐蚀产物堵塞管道事故严重威胁管道的正常运行,为研究管道中油流携水作用机制,从试验、理论两个角度对油流携水系统的特性进行研究。以柴油和水为介质,在内径27 mm的水平-上倾管流试验系统上对上倾管段0.5 m位置处的出水量以及临界油相流量(出水量不为零时的最小油相流量)进行测量,同时根据试验模型,基于油水两相动量方程和光滑分层流稳定的条件,建立水相厚度梯度的计算模型,对水平测试段中相界面分布进行分析,对出水量以及临界油相流量进行预测。结果表明:新模型能很好地预测两参数的变化;在油流携水系统中,油相处于层流状态时,建立的水相厚度梯度模型能很好地预测相界面分布。  相似文献   
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R B Clark  K A Gration  P N Usherwood 《Nature》1979,280(5724):679-682
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120.
利用金属有机物化学气相沉积法(MOCVD)制备了转化效率达27.1%的GaInP/GaAs/Ge三结叠层电池, 并对其光谱响应的温度特性进行了测量研究. 通过光谱响应曲线观察到各子电池的吸收边随温度升高发生红移, 这主要归因于电池材料禁带宽度的变窄效应. 根据光谱响应数据计算得到的GaInP/GaAs/Ge叠层电池各子电池在室温下的短路电流密度分别为12.9, 13.7和17 mA/cm2, 且叠层电池的短路电流密度的温度系数为8.9 μA/(cm2·℃). 最后, 根据叠层电池的串联结构推导了其电压温度系数为-6.27 mV/℃.  相似文献   
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