Chiral recognition of aromatic compounds by β-cyclodextrin based on bimodal complexation

The chiral recognition of the selected aromatic chiral compounds by native -cyclodextrin (-CD) based on bimodal complexation was studied using a flexible docking algorithm FDOCK. A quantitative empirical free energy relationship model was employed to predict the complex stability constants and the preferred binding modes. The results showed that the calculated complex stability constants are in good agreement with the experimental data. Furthermore, the main force responsible for host-guest complexation is the van der Waals force and the chiral molecules are completely included into the -CD cavity. The chiral recognition for the selected aromatic chiral compounds is the result of the van der Waals force counterbalancing with the other effects, such as the electrostatic interaction and the hydrophobic effect.Figure The favorable structures for the inclusion complexes of (S)_phenylbutyric with -CD. View in the plane normal to the Z-axis. -CD is shown in surface and (S)_phenylbutyric in CPK representation.     

云南省褐飞虱早期迁入虫源及其发生大气背景分析

为了探明我国西南稻区褐飞虱早期迁入种群的虫源地,为后期预测和防治提供依据,通过对2007—2016年云南植保站4—5月份褐飞虱虫情进行分析,选取出云南省勐海、芒市、江城、师宗、麻栗坡、广南6个代表性站点,利用WRF-FlexPart耦合模式对2013年、2015年和2016年这些站点的早期迁入峰进行了数值模拟,得到近年来云南省褐飞虱早期迁入虫源的虫源地。选取了2013年褐飞虱早期迁入量较大的迁入峰进行了大气背景分析,结合峰期影响褐飞虱迁飞的大气动力场、温度场和相对湿度场,探讨了影响云南省褐飞虱早期迁入的大气背景。研究结果表明:(1)近年来云南省褐飞虱迁入的虫源主要来自缅甸,部分来自老挝和泰国,少数来自越南,还有极少量来自孟加拉国。(2)这一时期,当释放高度分别为1500、2000 m时,褐飞虱的迁飞高度分别集中在2216 m和2489 m,平均迁飞高度分别是2167、2454 m,从不同释放高度回推的褐飞虱迁飞高度的起伏趋势具有较好的一致性,表明模式能较好地反映系统性垂直气流和下垫面起伏对其上层三维流场和种群迁飞的影响。(3)选取2013年5月22—26日发生在云南勐海、麻栗坡和广南的一次典型褐飞虱迁入过程,分析了大气背景场对褐飞虱迁飞的影响,结果显示:受印缅低压控制或影响,高空从境外虫源区至云南降虫区有西南水平气流作为种群输送动力;温场在降虫区东北侧有"低温屏障墙"存在,阻止了种群的继续北迁;垂直速度场上虫源区有上升气流促使种群起飞迁出,降虫区有下沉气流促使种群降落;弱降水形成的拖曳下沉气流对降虫也十分有利;相对湿度场对此次迁飞过程不形成任何胁迫。     

Improved Repeated Confidence Bounds in Trials with a Maximal Goal

Repeated confidence intervals can be computed at every interim analysis of a flexible group sequential design without the need to stop the trial with a pre‐planned stopping rule. Often, however, there is a maximal goal such that the trial is surely stopped if this goal is reached. This induces a maximal stopping rule, and repeated confidence intervals are strictly conservative, when adhering to it. A modification is proposed which uniformly improves the one sided repeated confidence interval in such a situation. It preserves the monitoring character, and leads to uniformly smaller intervals, when reaching the maximal goal at an interim analysis. The modification is worked out for two stage designs and is indicated for multi‐stage trials. The extent of the improvement is quantified for two simple scenarios.     

Effect of Crystal Orientation and Conduction Band Grading of Absorber on Efficiency of Cu(In,Ga)Se2 Solar Cells Grown on Flexible Polyimide Foil at Low Temperature

Flexible Cu(In,Ga)Se₂ (CIGS) solar cells are developed on polyimide (PI) foil by using a three‐stage co‐evaporation method. To deposit CIGS on a PI substrate, low temperature deposition process (below 440 °C) is investigated. By optimizing the three‐stage process, power conversion efficiency (PCE) values of 12.1% and 13.6% are obtained at maximum process temperatures of 400 °C and 440 °C, respectively (without anti‐reflection coating). The CIGS absorber deposited at 400 °C is grown with (220)/(204) rather than (112) as its dominant growth orientation, accompanied by highly homogeneous crystal structure and phases. Admittance spectroscopy reveals that the defect levels were lower in the CIGS absorber with (220)/(204) dominant growth orientation, which could have contributed to the PCE of 12.1%. The CIGS solar cell deposited at a temperature of 440 °C exhibits worse defect characteristics compared to that fabricated at 400 °C. However, the CIGS solar cell fabricated below 440 °C exhibited marginal double‐grading of Ga/(Ga + In) in the absorber layer, which resulted in an improved PCE of 13.6%. This result implies that at a temperature below 440 °C, the double‐grading of Ga/(Ga + In) is the more dominant factor causing the PCE improvement above 13%.     

Group sequential and adaptive designs - a review of basic concepts and points of discussion

In recent times, group sequential and adaptive designs for clinical trials have attracted great attention from industry, academia and regulatory authorities. These designs allow analyses on accumulating data - as opposed to classical, "fixed-sample" statistics. The rapid development of a great variety of statistical procedures is accompanied by a lively debate on their potential merits and shortcomings. The purpose of this review article is to ease orientation in both respects. First, we provide a concise overview of the essential technical concepts, with special emphasis on their interrelationships. Second, we give a structured review of the current controversial discussion on practical issues, opportunities and challenges of these new designs.     

Applications of the molecular dynamics flexible fitting method

In recent years, cryo-electron microscopy (cryo-EM) has established itself as a key method in structural biology, permitting the structural characterization of large biomolecular complexes in various functional states. The data obtained through single-particle cryo-EM has recently seen a leap in resolution thanks to landmark advances in experimental and computational techniques, resulting in sub-nanometer resolution structures being obtained routinely. The remaining gap between these data and revealing the mechanisms of molecular function can be closed through hybrid modeling tools that incorporate known atomic structures into the cryo-EM data. One such tool, molecular dynamics flexible fitting (MDFF), uses molecular dynamics simulations to combine structures from X-ray crystallography with cryo-EM density maps to derive atomic models of large biomolecular complexes. The structures furnished by MDFF can be used subsequently in computational investigations aimed at revealing the dynamics of the complexes under study. In the present work, recent applications of MDFF are presented, including the interpretation of cryo-EM data of the ribosome at different stages of translation and the structure of a membrane-curvature-inducing photosynthetic complex.     

A simple and flexible Holm gatekeeping procedure

Major objectives of a clinical trial are commonly stated in a hierarchical order as primary and secondary. The parallel gatekeeping testing strategy provides an opportunity to assess secondary objectives when all or partial primary objectives are achieved. The current available gatekeeping procedures have different pros and cons so users either need to justify the assumption associated with some procedures or tolerate suboptimal power performance of other procedures. By applying the Holm test with a flexible alpha splitting technique, we propose a procedure which (1) is powerful for assessing the primary objectives, (2) can be used when no assumption can be made on the dependency structure of test statistics, and (3) has the full flexibility to allocate user-preferred alpha to assess the secondary objectives based on the number of primary objectives achieved. A real clinical trial example is used for illustration of the proposed procedure.     

Structural model of ligand-G protein-coupled receptor (GPCR) complex based on experimental double mutant cycle data: MT7 snake toxin bound to dimeric hM1 muscarinic receptor

The snake toxin MT7 is a potent and specific allosteric modulator of the human M1 muscarinic receptor (hM1). We previously characterized by mutagenesis experiments the functional determinants of the MT7-hM1 receptor interaction (Fruchart-Gaillard, C., Mourier, G., Marquer, C., Stura, E., Birdsall, N. J., and Servent, D. (2008) Mol. Pharmacol. 74, 1554–1563) and more recently collected evidence indicating that MT7 may bind to a dimeric form of hM1 (Marquer, C., Fruchart-Gaillard, C., Mourier, G., Grandjean, O., Girard, E., le Maire, M., Brown, S., and Servent, D. (2010) Biol. Cell 102, 409–420). To structurally characterize the MT7-hM1 complex, we adopted a strategy combining double mutant cycle experiments and molecular modeling calculations. First, thirty-three ligand-receptor proximities were identified from the analysis of sixty-one double mutant binding affinities. Several toxin residues that are more than 25 Å apart still contact the same residues on the receptor. As a consequence, attempts to satisfy all the restraints by docking the toxin onto a single receptor failed. The toxin was then positioned onto two receptors during five independent flexible docking simulations. The different possible ligand and receptor extracellular loop conformations were described by performing simulations in explicit solvent. All the docking calculations converged to the same conformation of the MT7-hM1 dimer complex, satisfying the experimental restraints and in which (i) the toxin interacts with the extracellular side of the receptor, (ii) the tips of MT7 loops II and III contact one hM1 protomer, whereas the tip of loop I binds to the other protomer, and (iii) the hM1 dimeric interface involves the transmembrane helices TM6 and TM7. These results structurally support the high affinity and selectivity of the MT7-hM1 interaction and highlight the atypical mode of interaction of this allosteric ligand on its G protein-coupled receptor target.     

Synthesis, crystal structures and magnetic behavior of two 3D coordination polymers using N-(4/3-carboxyphenyl)iminodiacetic acids as bridging ligands

Research on structure and magnetic properties of polynuclear metal complexes to understand the structural and chemical factors governing the electronic exchange coupling mediated by multi-atom bridging ligands is of growing interest. Hydrothermal treatment of Ni(NO₃)₂·6H₂O with N-(4-carboxyphenyl)iminodiacetic acid [N-4(H₃CPIDA)] at 150 °C yielded a 3D coordination polymer of general formula [Ni₃{N-4(CPIDA)}₂(H₂O)₃]·6H₂O (1). An analogous network of general formula [Co₃{N-3(CPIDA)}₂(H₂O)₃]·3H₂O (2) was synthesized using N-(3-carboxyphenyl)iminodiacetic acid [N-3(H₃CPIDA)] in combination with Co(NO₃)₂·6H₂O under identical reaction condition. Both the complexes contain trinuclear secondary building unit, and crystallized in monoclinic system with space groups C2/c (1) and P2₁/c (2), respectively. Variable temperature magnetic characterization of these complexes in the temperature range of 2-300 K indicated the presence of overall ferromagnetic and antiferromagnetic behavior for 1 and 2, respectively. Density functional theory calculations (B3LYP functional) were performed for further insight on the trinuclear units to provide a qualitative theoretical interpretation on the overall magnetic behavior of the complexes 1 and 2.     

微通道经皮肾镜与输尿管软镜碎石取石术对输尿管上段结石患者血液流变学及男性性功能指标的影响

摘要 目的：以血液流变学及男性性功能指标为主要观察指标分析微通道经皮肾镜取石术（MPCNL）与输尿管软镜碎石取石术（FURL）在输尿管上段结石（UUC）中的应用价值。方法：将80例男性UUC患者按简单随机化法分MPCNL组、FURL组各40例;比较两组清石率、血液流变学、性功能指标及不良反应。结果：两组术后1w（82.50% vs 85.00%）、术后1mo（92.50% vs 97.50%）、术后3mo（100.00% vs 100.00%）的清石率无统计学意义（P＞0.05）。FURL组术后1天、术后7天的血液流变学指标水平均低于MPCNL组（P＜0.05）。两组术后男性性功能指标较术前显著改善,但FURL组术后3mo、6mo的男性性功能指标改善更显著（P＜0.05）。结论：对于UUC患者,MPCNL和FURL均能有效清除结石,都是安全有效的方法,但FURL较MPCNL对患者术后血液流变学的影响更小,且更利于术后性功能的恢复。