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.     

基于物联网终端管理云平台的大数据运维

近年来,随着快递物流、新零售、医疗卫生等行业信息化的快速发展,智能移动终端解决方案迅速普及,基于Android操作系统的智能移动终端被广泛应用。企业IT架构不断扩展,同时网络情况变得更加复杂,分支机构众多的大型企业这种情况能加明显。为了保证终端用户的良好体验以及数据的准确性和实效性,终端运维工作愈加困难。在运维过程中虽然已经运用自动化工具,但是管理系统时时采集、加工以及分析数据对运维工作是个巨大挑战。     

The challenges of COVID-19 control policies for sustainable development of business: Evidence from service industries

Such large-scale disruptions as the pandemic increase the uncertainty and risk related to business. Therefore, the business continuity management (BCM) has become an essential technical solution for enterprise emergency response. Since the beginning of 2020, the COVID-19 has spread worldwide at an alarming rate causing many threats to sustainable development of the business sector. The decline in consumer demand has hugely impacted service industries, such as wholesale and retail sales, tourism. Enterprise production and operations have faced severe challenges. In this study, we develop a risk factor analysis of BCM under the presence of COVID-19 in China. Based on a statistical survey of 940 enterprises in Hangzhou City, China, this study employs ordinal logistic regression to explore the hindering effect of risk factors introduced by the epidemic on business performance. Then, the interpretive structure model (ISM) is applied to analyze the hierarchical structure of the factors under examination. The key factors influencing the enterprise production and operation during COVID-19 outbreak significantly differ across the sub-sectors of the service industry. Therefore, this paper assesses the resilience of the productive technologies and business models of different industries amid the pandemic. This paper proposes epidemic prevention and control strategy focusing on investment and government regulation to ensure sustainable business development.     

Optimal operation of cogeneration system coordinated by aggregator for providing the demand and supply regulation capacity

Recent growth of renewable energy generations with natural variability, such as photovoltaic generation and wind turbine generation, would make the demand and supply control in a whole power system more difficult, and therefore, alternatives for demand and supply regulation resources would be required. The authors focus on cogeneration system (CGS) as one of regulation resources. In order to procure adequate volume of regulation capability, an aggregator coordinates a number of CGSs efficiently and flexibly considering the wide variety of electricity/thermal demands of CGS owners. This paper proposes a novel optimal operation strategy of CGS coordinated by the aggregator considering the energy balance and operation cost of individual CGS owner. This paper also demonstrates the availability of CGSs for regulation capability by numerical case studies in which the actual consumption profile is employed.     

施工现场标准化管理探讨

通过对神华宁煤400万t/a煤化工副产品深加工综合利用项目60万t/a聚丙烯装置施工作业现场的标准化研究,从技术团队的选择、计划进度控制、现场施工管理、文档资料规范等几个方面,探讨施工作业现场标准化作业的方法,为提高施工作业现场管理提供一些有益的建议。     

基于Hadoop的电力运维审计系统的设计

国家电网公司信息化程度越来越高，单机运维审计系统产生的数据量日益增多，对海量数据高效率存储分析性能严重下降，系统稳定性降低。为满足国家电网当前对运维审计系统数据存储分析以及系统稳定性的需求，在Hadoop开源架构的基础上，本文提出基于Hadoop集群的海量数据分布式存储方法和基于Heartbeat的心跳检测技术，实现基于Hadoop的电力运维审计系统。〖JP2〗实验测试结果表明，基于Hadoop的电力运维审计系统相比单机系统可用性提高了8.42%，大大提升了存储分析海量数据的性能，具有系统工作稳定和服务不间断等优势。     

航空装备保障智能化发展认识与探讨

自新一代人工智能技术迅猛发展以来，世界各国在智能领域动作频繁，军事化应用明显有加速之势，给装备保障带来了变革性发展的机遇。紧密围绕作战-装备-技术-保障之间的依托关系，从作战需求、装备特点、装备设计、诊断测试和技术驱动等五个角度梳理了装备保障发展的关键因素，给出了装备保障60余载发展历程的诸多原因和显著成果；通过对未来作战模式和未来作战平台保障需求的前瞻性判断，分析了未来作战需求和装备牵引装备保障转变的典型技术特征；并在装备保障领域人工智能技术的发展和应用现状总结分析的基础上，系统地提出了装备保障智能化发展的建设性意见和建议，为国内装备保障智能化发展探索了一个可能的技术方向。     

A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.     

基于时序数据的云网协同平台人工智能运维体系

云计算在企业应用中的拓展不但表现为平台规模的拓展，也表现为平台应用的延伸。“云网协同”和“微服务化”是当前企业云平台演进的重要趋势。随着企业信息化建设重要性的持续提升，微服务化云网协同平台的运行维护面临极大挑战。首先分析了平台运维面临的挑战，梳理了平台人工智能运维需求，提出了基于时序数据分析的平台人工智能运维技术体系，并给出了云网协同平台人工智能运维子系统参考设计。所提技术体系和系统设计具有实用性和推广性，可以作为企业云平台建设和优化的技术途径参考。