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.     

Binary Ti–Fe system. Part I: Experimental investigation at high pressure

The present work illustrates the effect of quasi-hydrostatic pressure on the positions and widths of the homogeneity ranges of the intermetallic phases TiFe and TiFe₂ at high temperatures. The experiments were performed with Ti–Fe diffusion couples that were heat treated in a multi-anvil press at 2.5 GPa. The solubility limits of the phases were derived from the concentration profiles that were measured using electron probe microanalysis. It was found that the homogeneity ranges of TiFe and TiFe₂ extend to higher titanium concentrations, if the pressure is applied. The positions of the phase boundaries of the intermetallics on the iron-rich side are not affected by the pressure. The accuracy of the experimental data including the homogeneity ranges and temperatures was verified by comparing the homogeneity ranges of β-Ti(Fe), α/δ-Fe(Ti) and γ-Fe measured in this study with the homogeneity ranges taken from literature. The pressure was calibrated using the pressure-induced phase transitions of bismuth.     

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.     

Identification of digital technologies and digitalisation trends in the mining industry

Digitalisation in mining refers to the use of computerised or digital devices or systems and digitised data that are to reduce costs, improve business productivity, and transform mining practices. However, it remains increasingly difficult for mining companies to decide which digital technologies are most relevant to their needs and individual mines. This paper provides an overview of digital technologies currently relevant to mining companies as presented and discussed by mining journals, the media and insight reports of leading consultancy agencies. Relevant technologies were systematically identified using text-mining techniques, and network analyses established the relations between significant technologies. Results demonstrated that currently 107 different digital technologies are pursued in the mining sector. Also, an analysis of the actual implementation of digital technologies in 158 active surface and underground mines reveals a limited uptake of digital technologies in general and that the uptake increases with the run-of-mine production. Large-scale mining operations appear to select and apply digital technologies suitable to their needs, whereas operations with lower production rates do not implement the currently available digital technologies to the same extent. These minor producers may require other digital transformation solutions tailored to their capabilities and needs and applicable to their scale of operations.     

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。     

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。     

Beneficial effects of wettability altering surfactants in oil-wet fractured reservoirs

In fractured reservoirs, an effective matrix-fracture mass transfer is required for oil recovery. Surfactants have long been considered for oil recovery enhancement, mainly in terms of their ability to reduce oil–water interfacial tension. These surfactants are effective when the fractured formations are water-wet, where capillary imbibition of surfactants from the fracture into the matrix contributes to oil recovery. However, another beneficial aspect of surfactants, namely their ability to alter wettability, remains to be explored and exploited. Surfactants capable of altering wettability can be especially beneficial in oil-wet fractured formations, where the surfactant in the fracture diffuses into the matrix and alters the wettability, enabling imbibition of even more surfactant into the matrix. This sequential process of initial diffusion followed by imbibition continues well into the matrix yielding significant enhancements in oil recovery.In order to test this hypothesis of sequential diffusion–imbibition phenomenon, Dual-Drop Dual-Crystal (DDDC) contact angle experiments have been conducted using fractured Yates dolomite reservoir fluids, two types of surfactants (nonionic and anionic) and dolomite rock substrates. A new experimental procedure was developed in which crude oil equilibrated with reservoir brine has been exposed to surfactant to simulate the matrix-fracture interactions in fractured reservoirs. This procedure enables the measurements of dynamic contact angles and oil–water interfacial tensions, in addition to providing the visual observations of the dynamic behavior of crude oil trapped in the rock matrix as it encounters the diffusing surfactant from the fractures. Both the measurements and visual observations indicate wettability alterations of the matrix surface from oil-wet to less oil-wet or intermediate wet by the surfactants. Thus this study is of practical importance to oil-wet fractured formations where surfactant-induced wettability alterations can result in significant oil recovery enhancements. In addition, this study has also identified the need to include contact angle term in the dimensionless Bond number formulations for better quantitative interpretation of rock–fluids interactions.