Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Strength and dilatancy behaviors of deep sands in Shanghai with a focus on grain size and shape effect

With rapid development of infrastructures like tunnels and open excavations in Shanghai, investigations on deeper soils have become critically important. Most of the existing laboratory works were focused on the clayey strata up to Layer 6 in Shanghai, i.e. at depth of up to 40 m. In this paper, Layers 7, 9, and 11, which were mostly formed of sandy soils at depth of up to 150 m, were experimentally investigated with respect to physico-mechanical behaviors. The stress–strain behaviors were analyzed by the consolidated drained/undrained (CD/CU) triaxial tests under monotonic loading. One-dimensional (1D) oedometer tests were performed to investigate the consolidation properties of the sandy soils. Specimens were prepared at three different relative densities for each layer. Also, the micro-images and particle size analyzers were used to analyze the shape and size of the sand grains. The influences of grain size, density, and angularity on the stress–strain behaviors and compressibility were also studied. Compared to the other layers, Layer 11 had the smallest mean grain size (D₅₀), highest compressibility, and lowest shear strength. In contrast, Layer 9 had the largest mean grain size, lowest compressibility, and highest shear strength. Layer 7 was of intermediate mean grain size, exhibiting more compressibility and less shear strength than that of Layer 9. Also, the critical state parameters and maximum dilatancy rate of different layers were discussed.     

土壤中石油污染物的脱附过程

文章中主要采用有机溶剂萃取法（OSE）对高浓度石油污染土壤进行修复，经过精馏操作，有效回收原油，建立脱附等温曲线，研究了石油污染物在土壤-有机溶剂两相间的迁移规律。     

Does decision quality (always) increase with the size of information samples? Some vicissitudes in applying the law of large numbers.

Adaptive decision making requires that contingencies between decision options and their relative assets be assessed accurately and quickly. The present research addresses the challenging notion that contingencies may be more visible from small than from large samples of observations. An algorithmic account for such a seemingly paradoxical effect is offered within a satisficing-choice framework. Accordingly, a choice is only made when the sample contingency describing the relative evaluation of the 2 options exceeds a critical threshold. Small samples, because of the high dispersion of their sampling distribution, facilitate above-threshold contingencies. Across a broad range of parameters, the resulting small-sample advantage in terms of hits is stronger than their disadvantage in false alarms. Computer simulations and experiments support the model predictions. The relative advantage of small samples is most apparent when information loss is low, when the threshold is high relative to the ecological contingency, and when the sampling process is self-truncated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Note of clarification on Scholten and Sherman (2006): Erratum.

Reports an error in "Tradeoffs and Theory: The Double-Mediation Model" by Marc Scholten and Steven J. Sherman (Journal of Experimental Psychology: General, 2006 May, Vol 135[2], 237-261). This article was inadvertently printed with the incorrect title. The original title was "Tradeoffs and Conflict: The Double-Mediation Model." This title highlights the relation between tradeoffs and conflict as investigated by the authors and accounted for by their model. However, readers are asked to refer to the article by the title with which it was printed to facilitate its retrieval.. (The following abstract of the original article appeared in record 2006-06642-006.) Most theories of decision making suggest that, when options imply tradeoffs between their attributes, conflict increases as tradeoff size increases, because greater sacrifices are to be incurred in choosing one option instead of another. An alternative view is that conflict decreases as tradeoff size increases, because stronger arguments can be made for any decision. The authors propose a unified model, the double-mediation model, which combines the mediating effects of sacrifice and argumentation. Our model generally predicts an inverse U-shaped relation between tradeoff size and conflict. Results support this prediction. Also, when the decision situation increases the mediating effect of sacrifice relative to that of argumentation, the relation between tradeoff size and conflict changes in an upward direction; conversely, when the decision situation increases the mediating effect of argumentation relative to that of sacrifice, the relation changes in a downward direction. Results support these predictions as well. Commonalities and differences between our model and other formulations are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

离心泵并联运行工况点的数值求解

建立了求解多台不同型号离心泵并联运行工况点的数学模型,给出了用数值计算中的“二分法”求解该模型的方法,并附有用Exce l计算的实例。     

双河油田注入水适应性及注水井酸化解堵研究

考察了双河油田双河联、江河联注入水堵塞地层的因素;膨胀性黏土，悬浮固体颗粒。细菌及悬浮污油。含膨胀性黏土的双河南、双河北及不含膨胀性黏土的双江岩心粉，在注入水中相对于地层水中的体积膨胀度分别为14．5％、11．1％及0．02％；注入100PV不含悬浮颗粒的等体积比地层水、注入水混合水使双河、双江岩心渗透率分别下降7％和4％、9％和7％。注入水中悬浮颗粒引起岩心渗透率下降，粒径越大、颗粒浓度越大、注入量越大，则渗透率越低。在粒径2．1μm或颗粒浓度3mg／L前后下降幅度变化较大。注入水中硫酸盐还原菌引起岩心渗透率下降，含菌量越大则渗透率开始下降时的注水量越小，注入含菌50个／L的水100PV使岩心渗透率下降7％。岩心对注水合油量敏感，注入含油量20mg／L的水50PV使岩心渗透率下降20％。在岩心注水实验中渗透率下降最严重的是双河南岩心，其次是双河北岩心．江河岩心较轻，注入精细过滤水的双河北岩心渗透率下降大大减少．说明悬浮固体是造成注水堵塞的主要因素。为了解除双河油田注水井的堵塞，研制了含黏土稳定剂、缓蚀剂、铁离子稳定剂、互溶剂的土酸液，与南阳油田使用的低伤害酸液一起，用于1口注水井的解堵，效果良好。图7表4参5。