Inhibitor Development against p7 Channel in Hepatitis C Virus

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.     

A 100 kHz Narrow-Pulse-Width Mid-Infrared Optical Parametric Oscillator Based on PPMgLN Crystal

We report a narrow pulse width optical parametric oscillator based on periodically poled MgO:LiNbO₃ (PPMgLN) with a high repetition rate under quasi-phase matched conditions. When the maximum pumping power of the 1,064-nm laser was 14.57 W, the acousto-optical (A-O) Q-switch repetition rate was 100 kHz, and the PPMgLN crystal grating period was 29.5 μm. A 1,474-nm signal light output power of 4.21 W and a 3,828 nm idler light output power of 1.547 W were obtained, corresponding to a pulse width of 9.52 ns and 9.65 ns, respectively. The overall optical–optical conversion efficiency was 39.5%. Additionally, by changing the temperature from 25°C to 150°C, a tunable signal wavelength of 1,474–1,499 nm and idler wavelength at 3,676–3,828 nm of the output laser were achieved.     

不同磁路电子回旋共振离子源引出实验

空间推进所用的电子回旋共振离子源(ECRIS)应具有体积小、效率高的特点. 本文研究的ECRIS使用永磁体环产生磁场, 有效减小了体积, 该离子源利用微波在磁场中加热电子, 电子与中性气体发生电离碰撞产生等离子体. 磁场在微波加热电子的过程中起关键作用, 同时影响离子源内等离子体的约束和输运. 通过比较四种磁路结构离子源的离子电流引出特性来研究磁场对10 cm ECRIS性能的影响. 实验发现: 在使用氩气的条件下, 特定结构的离子源可引出160 mA的离子电流, 最高推进剂利用率达60%, 最小放电损耗为120 W·A^-1; 所有离子源均存在多个工作状态, 工作状态在微波功率、气体流量、引出电压变化时会发生突变. 离子源发生状态突变时的微波功率、气体流量的大小与离子源内磁体的位置有关. 通过比较不同离子源的引出离子束流、放电损耗、气体利用率、工作稳定性的差异, 归纳了磁场结构对此种ECRIS引出特性的影响规律, 分析了其中的机理. 实验结果表明: 保持输入微波功率、气体流量、引出电压不变时, 增大共振区的范围、减小共振区到栅极的距离, 离子源能引出更大的离子电流; 减小共振区到微波功率入口、气体入口的距离能降低维持离子源高状态所需的最小微波功率和最小气体流量, 提高气体利用率, 但会导致放电损耗增大. 研究结果有助于深化对此类离子源工作过程的认识, 为其设计和性能优化提供参考.     

氟利昂F113分子在飞秒激光作用下的多光子电离解离动力学

大气臭氧层因吸收太阳紫外光, 是人类必不可少的保护伞. 氟利昂在太阳光辐射下解离生成破坏臭氧的游离态氯原子, 是破坏大气臭氧层的主要元凶之一. 本文利用飞行时间质谱技术和离子速度成像技术研究了氟利昂F113(三氟三氯乙烷)分子在800 nm 飞秒光作用下的多光子电离解离动力学. 利用飞行时间质谱探测技术, 得到了三氟三氯乙烷在该波长飞秒激光作用下发生多光子电离解离产生的碎片质谱. 通过荷质比对碎片质谱进行了详细的标定和分析. 在质谱上未发现母体离子, 所有观察到的离子都是由于激光脉冲作用下产生的碎片. 三个最主要的碎片离子是CFCl₂⁺, CF₂Cl⁺, C₂F₃Cl₂⁺. 通过飞行时间质谱标定, 发现并归属了多个解离通道. 三个主要的解离机理分别为: 1) C-Cl键断裂直接生产氯自由基的通道C₂F₃Cl₃⁺→C₂F₃Cl₂⁺+Cl; 2) C--C键断裂C₂F₃Cl₃⁺→CFCl₂⁺+CF₂Cl; 3) C--C键断裂C₂F₃Cl₃⁺→CF₂Cl⁺+CFCl₂. 利用离子速度成像技术对这三个主要通道产生的碎片离子进行成像, 得到了C₂F₃Cl₂⁺, CFCl₂⁺和CF₂Cl⁺离子的速度影像. 由C--Cl键断裂产生的碎片离子C₂F₃Cl₂^{+}的速度分布由两个高斯分布曲线拟合, 而由C--C键断裂产生的碎片离子CFCl₂⁺和CF₂Cl⁺可以用一个高斯曲线拟合. 通过影像分析得到了解离碎片的平动能分布和角向分布各向异性参数等详尽的动力学信息. 结合高精度密度泛函理论计算对解离动力学进行了进一步的分析和讨论.深入认识氟利昂的解离动力学可为进一步控制破坏臭氧层提供理论参考和实验依据.     

激光光源线宽对外差探测性能的影响

本文根据统计理论分析了激光线宽对外差探测结果的影响, 并讨论了激光线宽对杨氏干涉条纹对比度的影响. 本文基于解析结果做了数值仿真, 所得结果表明激光线宽增加时, 外差探测方式仍可以检测到中频信号, 但在线宽较大时, 受噪声影响无法准确地提取到中频频率. 为验证理论分析结果, 使用线宽为1 MHz的激光光源进行了8.1 km外场实验, 实验结果与数值分析结论一致, 即不会因为线宽增加而无法检测到中频信号. 文中所得结论对于外差探测光源的选择有重要指导意义, 因此根据测量目标的特性和测量要求, 可按照文中结论评估光源的线宽指标.     

Experimental simulation of the Unruh effect on an NMR quantum simulator

A triad mode resonance, or three-wave resonance, is typical of dynamical systems with quadratic nonlinearities. Suspended cables are found to be rich in triad mode resonant dynamics. In this paper, modulation equations for cable’s triad resonance are formulated by the multiple scale method. Dynamic conservative quantities, i.e., mode energy and Manley-Rowe relations, are then constructed. Equilibrium/dynamic solutions of the modulation equations are obtained, and full investigations into their stability and bifurcation characteristics are presented. Various bifurcation behaviors are detected in cable’s triad resonant responses, such as saddle-node, Hopf, pitchfork and period-doubling bifurcations. Nonlinear behaviors, like jump and saturation phenomena, are also found in cable’s responses. Based upon the bifurcation analysis, two interesting properties associated with activation of cable’s triad resonance are also proposed, i.e., energy barrier and directional dependence. The first gives the critical amplitude of high-frequency mode to activate cable’s triad resonance, and the second characterizes the degree of difficulty for activating cable’s triad resonance in two opposite directions, i.e., with positive or negative internal detuning parameter.     

Excitation dependent quenching of luminescence in LED phosphors

Droop, the decrease of efficiency with increased power density, became a major topic with InGaN LEDs, after its introduction in 2007. This paper provides insight into droop in localized center luminescence phosphors, exemplified here by Eu²⁺ doped materials. This topic is of increasing importance, as high brightness blue LEDs have reached outputs >1 W/mm². The nonlinearities in phosphor quantum efficiency result in drive‐dependent color point shift and reduction of overall efficiency of phosphor converted white LEDs which utilize Eu²⁺ activated phosphors. The efficiency quenching can be traced back to two processes, well‐known in laser physics, excited state absorption or/and cross relaxation by Foerster/Dexter transfer. Both processes lead to reduction in phosphor efficiency, but they can be differentiated. Understanding the root cause of efficiency quenching opens ways to minimize the practical consequences. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Observation of large low‐field magnetoresistance in spinel cobaltite: A new half‐metal

Low‐field magnetoresistance is an effective and energy‐saving way to use half‐metallic materials in magnetic reading heads and magnetic random access memory. Common spin‐polarized materials with low field magnetoresistance effect are perovskite‐type manganese, cobalt, and molybdenum oxides. In this study, we report a new type of spinel cobaltite materials, self‐assembled nanocrystalline NiCo₂O₄, which shows large low field magnetoresistance as large as –19.1% at 0.5 T and –50% at 9 T (2 K). The large low field magnetoresistance is attributed to the fast magnetization rotation of the core nanocrystals. The surface spin‐glass is responsible for the observed weak saturation of magnetoresistance under high fields. Our calculation demonstrates that the half‐metallicity of NiCo₂O₄ comes from the hopping e_g electrons within the tetrahedral Co‐atoms and the octahedral Ni‐atoms. The discovery of large low‐field magnetoresistance in simple spinel oxide NiCo₂O₄, a non‐perovskite oxide, leads to an extended family of low‐field magnetoresistance materials. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

p-Wave Feshbach molecules

We have produced and detected molecules using a p-wave Feshbach resonance between 40K atoms. We have measured the binding energy and lifetime for these molecules and we find that the binding energy scales approximately linearly with the magnetic field near the resonance. The lifetime of bound p-wave molecules is measured to be 1.0+/-0.1 ms and 2.3+/-0.2 ms for the ml=+/-1 and ml=0 angular momentum projections, respectively. At magnetic fields above the resonance, we detect quasibound molecules whose lifetime is set by the tunneling rate through the centrifugal barrier.     

Critical phenomena in head-on collisions of neutron stars

We find type I critical collapses of compact objects modeled by a polytropic equation of state (EOS) with a polytropic index Gamma=2 without the ultrarelativistic assumption. The object is formed in head-on collisions of neutron stars. Further, we show that the critical collapse can occur due to a change of the EOS, without fine-tuning of initial data. This opens the possibility that a neutron-star-like compact object, not just those formed in a collision, may undergo a critical collapse in processes which slowly change the EOS, such as cooling.