Full Envelope Research Articles

Efficient Capture and Detection of Zika Virion by Polyclonal Antibody Against Prokaryotic Recombinant Envelope Protein

Background: The outbreak of Zika virus (ZIKV) in many countries caused alarming numbers of babies born with microcephalus and severe neurologic disorders, however, the methods for the detection of the ZIKV are limited at present. Objectives: The aim of this study was to produce polyclonal antibody against full length envelop protein of ZIKV (ZIKV-E protein) in prokaryotic system and to evaluate its efficacy to capture ZIKV virion. Methods: The recombinant full length ZIKV-E protein was purified and then used as an immunogen to vaccinate BALB/c mice to produce polyclonal antibody. Protein A/G coated magnetic beads were coated with the polyclonal antibody to capture the ZIKV virion in the culture medium of Vero cells infected with ZIKV. The products of immunoprecipitation were further used for Western Blot, Loop-mediated isothermal amplification (LAMP), and PCR assay. Results: Western Blot and indirect immunofluorescence analysis showed that the mouse polyclonal antibody could react specifically with the native E protein in Vero cells infected with ZIKV. The results of Western Blot, Immunocaptured-LAMP (IC-LAMP), and Immunocaptured-PCR (IC-PCR) showed that polyclonal antibody of ZIKV-E recombinant protein can capture ZIKV virion specifically, however, the polyclonal antibody against the ZIKV-NS1, Shigella, and Salmonella without such a function. Conclusions: These findings may provide the basis for the development of the rapid diagnostic kits such as, IC-PCR, IC-LAMP, and sandwich ELISA. The serum virion capture activity elicited by prokaryotic expressed recombinant ZIKV-E protein may also provide a basis for further preparation of neutralizing antibody and protein subunit vaccine candidate against ZIKV.

Neural network based online predictive guidance for high lifting vehicles

In this paper, a data-driven online entry guidance framework is proposed. Based on the proposed framework, a novel neural network based online predictive guidance algorithm for high lifting vehicles is developed, which combines the benefits of the existing predictive guidance and the neural network predictor. By introducing the neural network predictor, the proposed algorithm can effectively overcome the long-standing contradiction between guidance accuracy and real-time guidance of existing numerical predictive guidance methods. Take the augmented predictor–corrector guidance algorithm as guidance pattern, a large number of sample trajectory data can be generated by performing full envelop trajectory simulations with different perturbation terms. Based on the sample data, the mapping relationship between the real-time flight states of high lifting vehicles and guidance commands is approximated by multi-layer feedforward neural network. By substituting the off-line trained neural network predictor for the trajectory integrations of each guidance cycle in the augmented algorithm, the proposed algorithm can successfully realize the online precision guidance for high lifting vehicles. The simulation results for nominal and dispersed cases show that the proposed algorithm has better performance on real-time capability and robustness than the existing numerical predictive guidance methods, and it is suitable for engineering practice.

Analytical representation of nonlinear Froude-Krylov forces for 3-DoF point absorbing wave energy devices

Accurate and computationally efficient mathematical models are fundamental for designing, optimizing, and controlling wave energy converters. Many wave energy devices exhibit significant nonlinear behaviour over their full operational envelope, so nonlinear models may become indispensable.Froude-Krylov nonlinearities are of great importance in point absorbers but, in general, their calculation requires an often unacceptable increase in model complexity/computational time. However, for axisymmetric bodies, it is possible to describe the whole geometry analytically, thereby allowing faster calculation of nonlinear Froude-Krylov forces.In this paper, a convenient parametrization of axisymmetric body geometries is proposed, applicable to devices moving in surge, heave, and pitch. While, in general, Froude-Krylov integrals must be solved numerically, by assuming small pitch angles, it is possible to simplify the problem, and achieve a considerably faster algebraic solution. However, both nonlinear models compute in real-time.The framework presented in the paper offers flexibility in terms of computational and fidelity levels, while still representing important nonlinear phenomena such as parametric pitch instability. Models with lower computational requirements may be more suitable for repetitive calculations, such as real-time control, or long-term power production assessment, while higher fidelity models may be more appropriate for maximum load estimation, or short-term power production capability assessment.

Design and Implementation of a Hybrid UAV With Model-Based Flight Capabilities

Hybrid UAV is an attractive design concept in the last decade for its superiority in combining vertical takeoff and landing (VTOL) and cruise flight capabilities. In this paper, we present a systematic design methodology from bottom up for an innovative tail-sitter UAV platform, named J-Lion. Implementation details are included with all design considerations and tradeoffs. All subsystem dynamics is investigated to constitute the dynamics model with a unified form for full envelope. Model-based VTOL and full envelope flights are realized with the obtained dynamics model and sophisticated flight control techniques. Experiment results successfully prove the effectiveness of our design concept and methodology.

Comparison of plastic, high density carbon, and beryllium as indirect drive NIF ablators

Detailed radiation hydrodynamic simulations calibrated to experimental data have been used to compare the relative strengths and weaknesses of three candidate indirect drive ablator materials now tested at the NIF: plastic, high density carbon or diamond, and beryllium. We apply a common simulation methodology to several currently fielded ablator platforms to benchmark the model and extrapolate designs to the full NIF envelope to compare on a more equal footing. This paper focuses on modeling of the hohlraum energetics which accurately reproduced measured changes in symmetry when changes to the hohlraum environment were made within a given platform. Calculations suggest that all three ablator materials can achieve a symmetric implosion at a capsule outer radius of ∼1100 μm, a laser energy of 1.8 MJ, and a DT ice mass of 185 μg. However, there is more uncertainty in the symmetry predictions for the plastic and beryllium designs. Scaled diamond designs had the most calculated margin for achieving symmetry and the highest fuel absorbed energy at the same scale compared to plastic or beryllium. A comparison of the relative hydrodynamic stability was made using ultra-high resolution capsule simulations and the two dimensional radiation fluxes described in this work [Clark et al., Phys. Plasmas 25, 032703 (2018)]. These simulations, which include low and high mode perturbations, suggest that diamond is currently the most promising for achieving higher yields in the near future followed by plastic, and more data are required to understand beryllium.

Seismic probing of the first dredge-up event through the eccentric red-giant and red-giant spectroscopic binary KIC 9163796

Context.Binaries in double-lined spectroscopic systems (SB2) provide a homogeneous set of stars. Differences of parameters, such as age or initial conditions, which otherwise would have strong impact on the stellar evolution, can be neglected. The observed differences are determined by the difference in stellar mass between the two components. The mass ratio can be determined with much higher accuracy than the actual stellar mass.Aim.In this work, we aim to study the eccentric binary system KIC 9163796, whose two components are very close in mass and both are low-luminosity red-giant stars.Methods.We analysed four years ofKeplerspace photometry and we obtained high-resolution spectroscopy with theHermesinstrument. The orbital elements and the spectra of both components were determined using spectral disentangling methods. The effective temperatures, and metallicities were extracted from disentangled spectra of the two stars. Mass and radius of the primary were determined through asteroseismology. The surface rotation period of the primary is determined from theKeplerlight curve. From representative theoretical models of the star, we derived the internal rotational gradient, while for a grid of models, the measured lithium abundance is compared with theoretical predictions.Results.From seismology the primary of KIC 9163796 is a star of 1.39 ± 0.06M⊙, while the spectroscopic mass ratio between both components can be determined with much higher precision by spectral disentangling to be 1.015 ± 0.005. With such mass and a difference in effective temperature of 600 K from spectroscopy, the secondary and primary are, respectively, in the early and advanced stage of the first dredge-up event on the red-giant branch. The period of the primary’s surface rotation resembles the orbital period within ten days. The radial rotational gradient between the surface and core in KIC 9163796 is found to be 6.9−1.0+2.0. This is a low value but not exceptional if compared to the sample of typical single field stars. The seismic average of the envelope’s rotation agrees with the surface rotation rate. The lithium’abundance is in agreement with quasi rigidly rotating models.Conclusions.The agreement between the surface rotation with the seismic result indicates that the full convective envelope is rotating quasi-rigidly. The models of the lithium abundance are compatible with a rigid rotation in the radiative zone during the main sequence. Because of the many constraints offered by oscillating stars in binary systems, such objects are important test beds of stellar evolution.

Feedforward Control for Wind Turbine Load Reduction with Pseudo-LIDAR Measurement

A gain-scheduled feedforward controller, based on pseudo-LIDAR (light detection and ranging) wind speed measurement, is designed to augment the baseline feedback controller for wind turbine’s load reduction in above rated operation. The pseudo-LIDAR measurement data are generated from a commercial software – Bladed using a designed sampling strategy. The nonlinear wind turbine model has been simplified and linearised at a set of equilibrium operating points. The feedforward controller is firstly developed based on a linearised model at an above rated wind speed, and then expanded to the full above rated operational envelope by employing gain scheduling strategy. The combined feedforward and baseline feedback control is simulated on a 5 MW industrial wind turbine model. Simulation studies demonstrate that the proposed control strategy can improve the rotor and tower load reduction performance for large wind turbines.

The applicability of J-integral approach in the determination of mixed-mode fracture energy in a ductile adhesive

In this work, a J-integral-based data reduction approach was used for fracture characterisation of a ductile two-component epoxy adhesive with steel adherends under mixed-mode loading. The applied method is a closed-form relation which requires only rotation angle of the load introduction points and the applied load as input. Double Cantilever Beam (DCB) tests as well as Mixed Mode Bending (MMB) tests (with different mixed-mode ratios) were carried out to achieve a wide range of mode-mixity. Based on the measured values of fracture toughness Gc, the full fracture envelope of the adhesive was developed by using the Benzeggagh-Kenane (B-K) fracture criterion. Good agreement between the FE and experimental load-displacement curves proved that the applied method is accurately capable of determining the fracture toughness of the adhesive. The proposed approach shows high potential to account the dissipated energy in the fracture process zone in the ductile adhesives.

Thermodynamics of the carbon dioxide plus argon (CO2 + Ar) system: An improved reference mixture model and measurements of vapor-liquid, vapor-solid, liquid-solid and vapor-liquid-solid phase equilibrium data at the temperatures 213–299 K and pressures up to 16 MPa

Phase equilibrium behavior of the carbon dioxide and argon system has been investigated at the temperatures 213, 223, 243, 263, 273, 283, and 299 K. The full vapor-liquid equilibria phase envelope has been measured at all temperatures using an analytical technique where the compositions of both the liquid and vapor phase have been measured. In addition, the fluid compositions at the three-phase line and phase equilibria involving solids at 213 K have been measured. The three-phase line was determined at 213 K with an estimated uncertainty of 2 kPa. Otherwise, the estimated uncertainty is better than 13 mK for the temperature measurements, 3.2 kPa for the pressure measurements, and 0.12% in total combined uncertainty in terms of mole fraction for all the 107 measured data points. The new data have been compared with existing models, and estimates for the critical points of the 7 isotherms have been made. Together with recently established experimental results for homogeneous density, speed of sound, and dew-point pressure, the vapor-liquid-equilibrium data were used to develop an improved Helmholtz-energy-explicit mixture model. This new model enables the calculation of highly-accurate data for all types of thermodynamic properties. Its development is part of the ongoing work on setting up an extended multi-fluid mixture model for the description of carbon-dioxide-rich mixtures with various impurities as relevant for CCS applications.

Coupling Fault Feature Extraction Method Based on Bivariate Empirical Mode Decomposition and Full Spectrum for Rotating Machinery

To accurately extract the fault characteristics of vibration signals of rotating machinery is of great significance to the unit online monitoring and evaluation. However, because the current feature extraction methods are mainly for single channel, the results of feature extraction are often inaccurate. To this end, a coupling fault feature extraction method based on bivariate empirical mode decomposition (BEMD) and full spectrum is proposed for rotating machinery. Firstly, the two-dimensional orthogonal signal obtained by orthogonal sampling technique is decomposed by bivariate empirical mode decomposition to obtain the intrinsic mode function with phase information. In order to obtain the sensitive modal components, the sensitivity coefficients are constructed on the basis of mutual information. Then, the sensitivity coefficient of each intrinsic mode function is calculated, and the intrinsic mode function with the larger sensitive coefficient is selected as the sensitive component. Finally, the full spectrum of the sensitive component is obtained using the full vector envelope technique, so as to get a comprehensive and accurate characteristic component. The results of simulations experiment and an application example show that this method can extract the fault characteristic component of the rotating machinery comprehensively and accurately. It is of great significance to realize the accurate diagnosis of coupling faults of rotating machinery.

Multiobjective optimization–based fault‐tolerant flight control system design

SummaryThe loss of measurements used for controller scheduling or envelope protection in modern flight control systems due to sensor failures leads to a challenging fault‐tolerant control law design problem. In this article, an approach to design such a robust fault‐tolerant control system, including full envelope protections using multiobjective optimization techniques, is proposed. The generic controller design and controller verification problems are derived and solved using novel multiobjective hybrid genetic optimization algorithms. These algorithms combine the multiobjective genetic search strategy with local, single‐objective optimization to improve convergence speed. The proposed strategies are applied to the design of a fault‐tolerant flight control system for a modern civil aircraft. The results of an industrial controller verification and validation campaign using an industrial benchmark simulator are reported.

A real-time capable mixing controlled combustion model for highly diluted conditions

A new real-time capable heat release rate model is presented that captures the high dilution effects of exhaust gas recirculation (EGR). The model is a Mixing Controlled Combustion type with enhancements to account for wall impingements, pilot injections, charge dilution caused by EGR at part load. The model was parameterised in two steps using a small set of measured data: the majority of model parameters were identified without EGR before identifying additional EGR related constants. The model performance was assessed based on key metrics: start of combustion; peak heat release and point of peak heat release and cylinder pressure. The model was evaluated over the full engine speed, load and EGR operating envelope and cylinder pressure metrics were predicted with R2 values above 0.94. With EGR, the model was able to predict qualitatively and quantitatively the performance whilst being parameterised by only by a small dataset. The model can be used to enable the engineering of robust new control algorithms and controller hardware for future engines using offline processes.

Cutting Edge: Innate Immune Augmenting Vesicular Stomatitis Virus Expressing Zika Virus Proteins Confers Protective Immunity.

Zika virus (ZIKV) has become a serious public health concern because of its link to brain damage in developing human fetuses. Recombinant vesicular stomatitis virus (rVSV) was shown to be a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. In this study, we generated rVSVs (wild-type and attenuated VSV with mutated matrix protein [VSVm] versions) that express either the full length ZIKV envelope protein (ZENV) alone or include the ZENV precursor to the membrane protein upstream of the envelope protein, and our rVSV-ZIKV constructs showed efficient immunogenicity in murine models. We also demonstrated maternal protective immunity in challenged newborn mice born to female mice vaccinated with VSVm-ZENV containing the transmembrane domain. Our data indicate that rVSVm may be a suitable strategy for the design of effective vaccines against ZIKV.

Dispersion-Induced Beam Instability in Circular Accelerators.

The envelope instability near the 90° phase advance in periodically focused space charge dominated beams is a well-known phenomenon in linear transport sections or linacs. The corresponding stop band is usually avoided because of the resulting strong mismatch oscillations and beam loss. We show that in circular accelerators or transport sections including bending magnets the instability is modified due to the effect of dispersion. Using the two-dimensional envelope equations extended by the dispersion equation we identify an additional stop band above 120°. For periodic focusing the stop band results from the confluence of an envelope mode with the newly identified coherent dispersion mode. Results from perturbation theory are compared with the full envelope model and particle-in-cell simulation, which all show good agreement. The newly identified mode has several implications and applications for the characterization of intense beams in circular machines.

Design and validation of an unmanned surface vehicle simulation model

In this paper we present a multiphysics simulation model of Halcyon, an autonomous unmanned surface vehicle (USV). The simulation model presented in this paper has been developed to rapidly progress the design, development and validation of Halcyon’s autonomy management system, particularly in challenging sea conditions. Using simulation for this purpose enables extensive testing across the full environmental operating envelope of the vessel, hence greatly reducing the need for real-world sea-trials. The simulator is comprised of a novel and comprehensive sea-surface wave environment model, a six degree of freedom nonlinear unified seakeeping and manoeuvring boat dynamics model, an actuation dynamics model, an autopilot and an interface with an autonomy management system. Results are presented that show good agreement between real-world and simulated sea-trials data.

Parametric sum envelope instability of periodically focused intense beams

The envelope instability is a second order parametric resonance with the periodic focusing and known to appear in space charge dominated beams near 90° phase advance per focusing period. We show in 2d approximation that space charge may also induce parametric “sum envelope instabilities” leading to simultaneous growth of envelopes or skew angles as well as emittances. This can happen by two-plane envelope coupling or by exciting a skew (“odd”) mode in an otherwise fully uncoupled linear lattice. At resonance, the two individual phase advances are split more or less symmetrically away from 90°, and exponential growth occurs. Results from perturbation theory are compared with full envelope models, particle-in-cell simulations, and smooth approximation stopband calculations, all showing very good agreement for realistic space charge parameters.

Genetic characterization of poxviruses in Camelus dromedarius in Ethiopia, 2011–2014

Camelpox and camel contagious ecthyma are infectious viral diseases of camelids caused by camelpox virus (CMLV) and camel contagious ecthyma virus (CCEV), respectively. Even though, in Ethiopia, pox disease has been creating significant economic losses in camel production, little is known on the responsible pathogens and their genetic diversity. Thus, the present study aimed at isolation, identification and genetic characterization of the causative viruses. Accordingly, clinical case observations, infectious virus isolation, and molecular and phylogenetic analysis of poxviruses infecting camels in three regions and six districts in the country, Afar (Chifra), Oromia (Arero, Miyu and Yabello) and Somali (Gursum and Jijiga) between 2011 and 2014 were undertaken. The full hemagglutinin (HA) and partial A-type inclusion protein (ATIP) genes of CMLV and full major envelope protein (B2L) gene of CCEV of Ethiopian isolates were sequenced, analyzed and compared among each other and to foreign isolates. The viral isolation confirmed the presence of infectious poxviruses. The preliminary screening by PCR showed 27 CMLVs and 20 CCEVs. The sequence analyses showed that the HA and ATIP gene sequences are highly conserved within the local isolates of CMLVs, and formed a single cluster together with isolates from Somalia and Syria. Unlike CMLVs, the B2L gene analysis of Ethiopian CCEV showed few genetic variations. The phylogenetic analysis revealed three clusters of CCEV in Ethiopia with the isolates clustering according to their geographical origins. To our knowledge, this is the first report indicating the existence of CCEV in Ethiopia where camel contagious ecthyma was misdiagnosed as camelpox. Additionally, this study has also disclosed the existence of co-infections with CMLV and CCEV.A comprehensive characterization of poxviruses affecting camels in Ethiopia and the full genome sequencing of representative isolates are recommended to better understand the dynamics of pox diseases of camels and to assist in the implementation of more efficient control measures.

Fragments of the V1/V2 domain of HIV-1 glycoprotein 120 engineered for improved binding to the broadly neutralizing PG9 antibody.

The V1/V2 domain of the HIV-1 envelope protein gp120 possesses two important epitopes: a glycan-dependent epitope recognized by the prototypic broadly neutralizing monoclonal antibody (bN-mAb), PG9, as well as an epitope recognized by non-neutralizing antibodies that has been associated with protection from HIV infection in the RV144 HIV vaccine trial. Because both of these epitopes are poorly immunogenic in the context of full length envelope proteins, immunization with properly folded and glycosylated fragments (scaffolds) represents a potential way to enhance the immune response to these specific epitopes. Previous studies showed that V1/V2 domain scaffolds could be produced from a few selected isolates, but not from many of the isolates that would be advantageous in a multivalent vaccine. In this paper, we used a protein engineering approach to improve the conformational stability and antibody binding activity of V1/V2 domain scaffolds from multiple diverse isolates, including several that were initially unable to bind the prototypic PG9 bN-mAb. Significantly, this effort required replicating both the correct glycan structure as well as the β-sheet structure required for PG9 binding. Although scaffolds incorporating the glycans required for PG9 binding (e.g., mannose-5) can be produced using glycosylation inhibitors (e.g., swainsonine), or mutant cell lines (e.g. GnTI(-) 293 HEK), these are not practical for biopharmaceutical production of proteins intended for clinical trials. In this report, we describe engineered glycopeptide scaffolds from three different clades of HIV-1 that bind PG9 with high affinity when expressed in a wildtype cell line suitable for biopharmaceutical production. The mutations that improved PG9 binding to scaffolds produced in normal cells included amino acid positions outside of the antibody contact region designed to stabilize the β-sheet and turn structures. The scaffolds produced address three major problems in HIV vaccine development: (1) improving antibody responses to poorly immunogenic epitopes in the V1/V2 domain; (2) eliminating antibody responses to highly immunogenic (decoy) epitopes outside the V1/V2 domain; and (3) enabling the production of V1/V2 scaffolds in a cell line suitable for biopharmaceutical production.

Molecular clock of HIV-1 envelope genes under early immune selection.

BackgroundThe molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.ResultsWe identified molecular clock signatures from 1587 previously published HIV-1 full envelope gene sequences obtained since acute infection in 15 subjects. Each subject’s sequence diversity linearly increased during the first 150 days post infection, with rates ranging from 1.54 times 10^{ - 5} to 3.91 times 10^{ - 5} with a mean of 2.69 times 10^{ - 5} per base per day. The rate of diversification for 12 out of the 15 subjects was comparable to the neutral evolution rate. While temporal diversification was consistent with evolution patterns in the absence of selection, mutations from the founder virus were highly clustered on statistically identified selection sites, which diversified more than 65 times faster than non-selection sites. By mathematically quantifying deviations from the molecular clock under various selection scenarios, we demonstrate that the deviation from a constant clock becomes negligible as multiple escape lineages emerge. The most recent common ancestor of a virus pair from distinct escape lineages is most likely the transmitted founder virus, indicating that HIV-1 molecular dating is feasible even after the founder viruses are no longer detectable.ConclusionsThe ability of HIV-1 to escape from immune surveillance in many different directions is the driving force of molecular clock persistence. This finding advances our understanding of the robustness of HIV-1’s molecular clock under immune selection, implying the potential for molecular dating.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0269-6) contains supplementary material, which is available to authorized users.

Multiple Introductions of Dengue 2 Virus Strains into Saudi Arabia from 1992 to 2014.

Dengue is a significant arboviral infection that represents a major public health concern worldwide. The infection is endemic in most parts of South East Asia, sub-Saharan Africa, and Latin America. Among the four dengue virus (DENV) serotypes, DENV-2 has been reported to be the predominant serotype in Saudi Arabia since 1992. However, virological and epidemiological data of DENV-2 from Saudi Arabia are severely deficient and require further investigations. Full genome sequencing of a recent DENV-2 isolate and phylogenetic analysis of all available DENV-2 sequences from Saudi Arabia. Based on full genome and envelope (E) gene sequence, we show that a recent isolate (DENV-2-Jeddah-2014) belongs to the Indian subcontinent lineage of the Cosmopolitan genotype with close similarity to recent strains from Pakistan. Interestingly, the E gene sequence of DENV-2-Jeddah-2014 isolate was slightly divergent from those previously identified in Saudi Arabia between 1992 and 2004 with three to nine amino acid (aa) substitutions. While our data show that the Cosmopolitan genotype is still circulating in Saudi Arabia, they highlight four distinct genetic groups suggesting at least four independent introductions into the Kingdom. The close clustering of DENV-2 isolates reported from Saudi Arabia between 1992 and 2014 with strains from countries providing the highest numbers of pilgrims attending either Hajj or Umrah pilgrimages (Indonesia, Pakistan, India) clearly suggests a role for pilgrims or expatriates coming from DENV endemic countries in DENV-2 importation into Saudi Arabia. Accordingly, continuous monitoring of the circulation of DENVs in Saudi Arabia must be implemented to undertake effective control and management strategies in the Kingdom. Screening of the pilgrims coming to perform Hajj and Umrah might help prevent the introduction of new DENV strains, which is expected to increase the burden of the disease not only in Saudi Arabia but also in other countries.