Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

VZV是一种广泛存在并且具有高度传染性的人类α-疱疹病毒。初次感染VZV可导致水痘，人群普遍易感（感染率约为61%～100%）。该病毒可在背根神经节潜伏感染，持续终生。夏宁邵教授团队长期开展VZV相关基础与新型疫苗研究，通过系统和精细探索建立了高效的VZV规模化培养和病毒颗粒纯化技术体系，成功获得高质量的VZV颗粒样品。首次揭示了疱疹病毒α家族的水痘-带状疱疹病毒（VZV）不同类型核衣壳的近原子分辨率结构，阐明了VZV核衣壳不同组成蛋白的相互作用网络与衣壳装配机制，可为进一步开展新型载体疫苗设计及抗病毒药物等研究提供重要支持。 我校博士后王玮、高级工程师郑清炳、博士生潘德全和俞海副教授为该论文共同第一作者，我校夏宁邵教授、程通副教授、李少伟教授以及美国罗格斯大学朱桦（Hua Zhu）教授、加利福尼亚大学洛杉矶分校周正洪（Z. Hong Zhou）教授为该论文的共同通讯作者。【Abstract】Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP—the largest among human herpesviruses—uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.This research was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402), the National Natural Science Foundation of China (no. 81871648, 81601762), the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences (no. 2019RU022) and the US National Institutes of Health (DE025567/028583). 该研究获得了国家自然科学基金、新药创制国家科技重大专项和传染病防治国家科技重大专项等资助

BDS/GPS Multi-Baseline Relative Positioning for Deformation Monitoring

The single-baseline solution (SBS) model has been widely adopted by the existing global navigation satellite system (GNSS) deformation monitoring systems due to its theoretical simplicity and ease of implementation. However, the SBS model neglects the mathematical correlation between baselines, and the accuracy and reliability can be degraded for baselines with long length, large height difference or frequent satellite signal occlusion. When monitoring large-area ground settlement or long-spanned linear objects such as bridges and railroads, multiple reference stations are frequently utilized, which can be exploited to improve the monitoring performance. Therefore, this paper evaluates the multi-baseline solution (MBS) model, and constrained-MBS (CMBS) model that has a prior constraint of the spatial-correlated tropospheric delay. The reliability and validity of the MBS model are verified using GPS/BDS datasets from ground settlement deformation monitoring with a baseline length of about 20 km and a height difference of about 200 m. Numerical results show that, compared with the SBS model, the MBS model can reduce the positioning standard deviation (STD) and root-mean-squared (RMS) errors by up to (47.4/51.3/66.2%) and (56.9/60.4/58.4%) in the north/east/up components, respectively. Moreover, the combined GPS/BDS positioning performance for the MBS model outperforms the GPS-only and BDS-only positioning models, with an average accuracy improvement of about 13.8 and 25.8%, with the highest accuracy improvement of about 41.6 and 43.8%, respectively. With the additional tropospheric delay constraint, the CMBS model improves the monitoring precision in the up direction by about 45.0%

Evaluation of Real-Time Kinematic Positioning and Deformation Monitoring Using Xiaomi Mi 8 Smartphone

Modern low-cost electronic devices can achieve high precision for global navigation satellite systems (GNSSs) and related applications. Recently, the pseudo-range and carrier phase have been directly obtained from a smartphone to establish a professional-level surveying device. Although promising results have been obtained by linking to an external GNSS antenna, the real-time kinematic (RTK) positioning performance requires further improvement when using the embedded smartphone antenna. We first investigate the observation quality characteristics of the Xiaomi Mi 8 smartphone. The carrier-to-noise-density ratio of L5/E5a signals is below that of L1/E1 signals, and the cycle slip and loss of lock are severe, especially for L5/E5a signals. Therefore, we use an improved stochastic model and ambiguity-resolution strategies to improve the short-baseline RTK positioning accuracy. Experimental results show that the ambiguity fixing rate can reach approximately 90% in 3 h of observations when using the embedded antenna, while the GPS/Galileo/BDS single-frequency combination is more suitable for smartphones. On the other hand, convergence takes 10–30 min, and the RTK positioning accuracy can reach 1 and 2 cm along the horizontal and vertical directions, respectively, if ambiguity is resolved correctly. Moreover, we verify the feasibility of using a mass-produced smartphone for deformation monitoring. Results from a simulated dynamic deformation experiment indicate that a smartphone can recognise deformations as small as 2 cm

Editorial for Special Issue “Precise GNSS Positioning and Navigation: Methods, Challenges, and Applications”

The Global Navigation Satellite System (GNSS) can provide users with high-precision positioning information continuously and benefits all walks of life, e [...

Intersystem Bias in GPS, GLONASS, Galileo, BDS-3, and BDS-2 Integrated SPP: Characteristics and Performance Enhancement as a Priori Constraints

Global navigation satellite systems (GNSSs) have been booming in recent years, and the space segment of all four of the GNSSs, including BDS (BDS-3/BDS-2), Galileo, GPS, and GLONASS, has almost been fully deployed at present. The single point positioning (SPP) technology, which is widely used in satellite navigation and low-accuracy positioning, can benefit from the multi-GNSS integration, but the additional intersystem bias (ISB) parameters should be introduced to ensure the compatibility among different GNSSs. In this study, the ISB estimates derived from four-system integrated SPP are carefully characterized, and the performance enhancement attributed to a priori ISB constraints by prediction for position solutions under open sky and constrained visibility environments is rigorously evaluated. The results indicate that the ISB between BDS-3 and BDS-2 cannot be ignored. The daily ISBs show step changes when encountering the replacement of receiver types, while it is not the case for the receiver firmware versions. The daily ISBs are roughly consistent for the stations equipped with the same type of receivers. The short-term stability of epochwise ISBs for GLONASS, Galileo, BDS-2, and BDS-3 with respect to GPS can be 2.335, 1.262, 1.741, and 1.532 ns, respectively, whereas the corresponding long-term stability for daily ISBs can be 1.258, 1.288, 2.713, and 2.566 ns, respectively. The single-day prediction accuracy of daily ISBs for GLONASS, Galileo, BDS-2, and BDS-3 with respect to GPS can be 1.055, 0.640, 1.242, and 0.849 ns, respectively. The improvements on positioning accuracy after introducing a priori ISB constraints can be over 20% at an elevation mask of 40° and 50° with a time span of ISB prediction of a day. As to the availability, it is only 64.0% for traditional four-system SPP under a cutoff elevation of 50°, while the corresponding availability is increased to approximately 90.0% after considering a priori ISB constraints. For completeness, the characteristics of ISBs estimated with the low-cost u-blox M8T receiver and the Xiaomi Mi8 smartphone as well as the contribution of a priori ISB constraints to the multisystem SPP solutions with these devices are also investigated

Assessment of IRNSS-Only Data Processing: Availability, Single-Frequency SPP and Short-Baseline RTK

The Indian Regional Navigation Satellite System (IRNSS) currently can provide independent positioning services with eight in-orbit satellites. This study provides a comprehensive assessment of IRNSS-only data processing, including the availability of satellite constellation, the performance of single-frequency single point positioning (SPP), and the performance of single-frequency short-baseline real-time kinematic (RTK) positioning. Regarding the availability of IRNSS-only case in its primary service areas, the average number of visible satellites is 6–8, and the average Position Dilution of Precision (PDOP) value falls between 3.3 and 6.2, under a service rate of nearly 100.0%. The datasets from 14 stations located in the IRNSS service areas spanning a week are used for position determination. The results show that under the IRNSS single-system case, the positioning accuracy of the SPP is 6.031, 6.015, and 9.668 m in the east, north, and up directions, respectively, and the mean positioning bias of short-baseline RTK is 5.4, −21.1, and −0.2 mm with a standard deviation (STD) error of 7.8, 19.2, and 29.0 mm in the three directions, respectively. For comparative analysis, the results of the GPS single-system and GPS/IRNSS dual-system combination cases are also presented. The positioning performance of IRNSS is inferior to that of GPS, and the performance improvement of GPS/IRNSS dual-system integrated solutions over GPS single-system solutions is not significant. Furthermore, based on the GPS/IRNSS dual-system solutions, the inter-system bias estimates from SPP, the code observation residuals from SPP, and the carrier phase observation residuals from short-baseline RTK are characterized

Assessment of IRNSS-Only Data Processing: Availability, Single-Frequency SPP and Short-Baseline RTK

The Indian Regional Navigation Satellite System (IRNSS) currently can provide independent positioning services with eight in-orbit satellites. This study provides a comprehensive assessment of IRNSS-only data processing, including the availability of satellite constellation, the performance of single-frequency single point positioning (SPP), and the performance of single-frequency short-baseline real-time kinematic (RTK) positioning. Regarding the availability of IRNSS-only case in its primary service areas, the average number of visible satellites is 6–8, and the average Position Dilution of Precision (PDOP) value falls between 3.3 and 6.2, under a service rate of nearly 100.0%. The datasets from 14 stations located in the IRNSS service areas spanning a week are used for position determination. The results show that under the IRNSS single-system case, the positioning accuracy of the SPP is 6.031, 6.015, and 9.668 m in the east, north, and up directions, respectively, and the mean positioning bias of short-baseline RTK is 5.4, −21.1, and −0.2 mm with a standard deviation (STD) error of 7.8, 19.2, and 29.0 mm in the three directions, respectively. For comparative analysis, the results of the GPS single-system and GPS/IRNSS dual-system combination cases are also presented. The positioning performance of IRNSS is inferior to that of GPS, and the performance improvement of GPS/IRNSS dual-system integrated solutions over GPS single-system solutions is not significant. Furthermore, based on the GPS/IRNSS dual-system solutions, the inter-system bias estimates from SPP, the code observation residuals from SPP, and the carrier phase observation residuals from short-baseline RTK are characterized

Real-Time Precise Point Positioning Using Tomographic Wet Refractivity Fields

The tropospheric wet delay induced by water vapor is a major error source in precise point positioning (PPP), significantly influencing the convergence time to obtain high-accuracy positioning. Thus, high-quality water vapor information is necessary to support PPP processing. This study presents the use of tomographic wet refractivity (WR) fields in PPP to examine their impacts on the positioning performance. Tests are carried out based on 1-year of 2013 global navigation satellite system (GNSS) observations (30 s sampling rate) from three stations with different altitudes in the Hong Kong GNSS network. Coordinate errors with respect to reference values at a 0.1 m level of convergence is used for the north, east, and up components, whilst an error of 0.2 m is adopted for 3D position convergence. Experimental results demonstrate that, in both static and kinematic modes, the tomography-based PPP approach outperforms empirical tropospheric models in terms of positioning accuracy and convergence time. Compared with the results based on traditional, Saastamoinen, AN (Askne and Nordis), and VMF1 (Vienna Mapping Function 1) models, 23–48% improvements of positioning accuracy, and 5–30% reductions of convergence time are achieved with the application of tomographic WR fields. When using a tomography model, about 35% of the solutions converged within 20 min, whereas only 23%, 25%, 25%, and 30% solutions converged within 20 min for the traditional, Saastamoinen, AN, and VMF1 models, respectively. Our study demonstrates the benefit to real-time PPP processing brought by additional tomographic WR fields as they can significantly improve the PPP solution and reduce the convergence time for the up component

Determination of Landslide Displacement Warning Thresholds by Applying DBA-LSTM and Numerical Simulation Algorithms

Numerical simulation has emerged as a powerful technique for landslide failure mechanism analysis and accurate stability assessment. However, due to the bias of simplified numerical models and the uncertainty of geomechanical parameters, simulation results often differ greatly from the actual situation. Therefore, in order to ensure the accuracy and rationality of numerical simulation results, and to improve landslide hazard warning capability, techniques and methods such as displacement back-analysis, machine learning, and numerical simulation are combined to create a novel landslide warning method based on DBA-LSTM (displacement back-analysis based on long short-term memory networks), and a numerical simulation algorithm is proposed, i.e., the DBA-LSTM algorithm is used to invert the equivalent physical and mechanical parameters of the numerical model, and the modified numerical model is used for stability analysis and failure simulation. Taking the Shangtan landslide as an example, the deformation mechanism of the landslide was analyzed based on the field monitoring data, and subsequently, the superiority of the DBA-LSTM algorithm was verified by comparing it with DBA-BPNN (displacement back-analysis based on back-propagation neural network); finally, the stability of the landslide was analyzed and evaluated a posteriori using the warning threshold calculated by the proposed method. The analytical results show that the displacement back-analysis based on the machine learning (DBA-ML) algorithm can achieve more than 95% accuracy, and the deep learning algorithm exemplified by LSTM had higher accuracy compared to the classical BPNN algorithm, meaning that it can be used to further improve the existing intelligent inversion theory and method. The proposed method calculates the landslide’s factor of safety (FOS) before the accelerated deformation to be 1.38 and predicts that the landslide is in a metastable state after accelerated deformation rather than in failure. Compared to traditional empirical warning models, our method can avoid false warnings and can provide a new reference for research on landslide hazard warnings