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Human papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent).1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20-26, 27-35, or 36-45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference -10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio 0.5.Among the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded -10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths.This study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.

The dominant N501Y mutation in the spike protein that SARS-CoV-2 virus uses to bind to the human ACE2 receptor were found in the UK, which has aroused global concern and worried. Mutations in spike protein may, in theory, result in more infectious and spreading more easily. In order to evaluate the broad-spectrum protective effect of the monoclonal antibodies(mAbs), we compared the neutralization activities of six prepared mAbs against SARS-CoV-2 with pseudovirus neutralization assay. Only one of them showed a decrease of 6 folds in neutralizing activity to N501Y mutant strain, compared with the wild type strain. We should continue to monitor emergence of new variants in different regions to study their infectivity and neutralization effect.

Pseudoviruses are useful virological tools because of their safety and versatility, especially for emerging and re-emerging viruses. Due to its high pathogenicity and infectivity and the lack of effective vaccines and therapeutics, live SARS-CoV-2 has to be handled under biosafety level 3 conditions, which has hindered the development of vaccines and therapeutics. Based on a VSV pseudovirus production system, a pseudovirus-based neutralization assay has been developed for evaluating neutralizing antibodies against SARS-CoV-2 in biosafety level 2 facilities. The key parameters for this assay were optimized, including cell types, cell numbers, virus inoculum. When tested against the SARS-CoV-2 pseudovirus, SARS-CoV-2 convalescent patient sera showed high neutralizing potency, which underscore its potential as therapeutics. The limit of detection for this assay was determined as 22.1 and 43.2 for human and mouse serum samples respectively using a panel of 120 negative samples. The cutoff values were set as 30 and 50 for human and mouse serum samples, respectively. This assay showed relatively low coefficient of variations with 15.9% and 16.2% for the intra- and inter-assay analyses respectively. Taken together, we established a robust pseudovirus-based neutralization assay for SARS-CoV-2 and are glad to share pseudoviruses and related protocols with the developers of vaccines or therapeutics to fight against this lethal virus.

Azo pigments with azo functional groups (-NN-) are commonly used in foods. Through rational design, here we report synthesis of a novel magnetic metal-organic framework (MOF-545) and the use of Fe

Referring to CATIA’s ‘assemblies + parts’ modeling method, CATIA-based BIM (Building Information Modeling) technology has been proposed for highway tunnel design in this paper. A tunnel BIM is created by CATIA, which is based on a real case in China, focusing on the following 3 aspects: (1) Creating tunnel bolts by UDF + Loop cyclic arrangement method; (2) Using Sketch Tracer module to create tunnel portal; (3) Parameter is used to create and call the Catalog database. Then, bolt collision inspection and U-shaped groove concrete statistics are conducted with the help of the tunnel BIM created. Finally, the finite element analysis of tunnel construction process is carried out through the CATIA-Midas interface. The results demonstrate that the CATIA-based BIM technology can well adapt to the characteristics of tunnel and have well potential applications in tunnel design.

Summary The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious but variants including A475V, L452R, V483A and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious whilst deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies., Highlights • Over 100 mutations were selected for analyses on their infectivity and antigenicity •The dominant D614G itself and combined with other mutations are more infectious •Ablation of both N331 and N343 glycosylation at RBD drastically reduced infectivity •Ten mutations such as N234Q, L452R, A475V, V483A was markedly resistant to some mAbs, Eighty natural variants and twenty-six glycosylation spike mutants of SARS-CoV-2 were analyzed in terms of infectivity and antigenicity using high throughput pseudovirus assay in conjunction with neutralizing antibodies.

The proliferation and development of chloroplasts are important for maintaining the normal chloroplast population in plant tissues. Most studies have focused on chloroplast maintenance in leaves. In this study, we identified a spontaneous mutation in a tomato mutant named suffulta (su), in which the stems appeared albinic while the leaves remained normal. Map-based cloning showed that Su encodes a DnaJ heat shock protein that is a homolog of the Arabidopsis gene AtARC6, which is involved in chloroplast division. Knockdown and knockout of SlARC6 in wild-type tomato inhibit chloroplast division, indicating the conserved function of SlARC6. In su mutants, most mesophyll cells contain only one or two giant chloroplasts, while no chloroplasts are visible in 60% of stem cells, resulting in the albinic phenotype. Compared with mature tissues, the meristem of su mutants suggested that chloroplasts could partially divide in meristematic cells, suggesting the existence of an alternative mechanism in those dividing cells. Interestingly, the adaxial petiole cells of su mutants contain more chloroplasts than the abaxial cells. In addition, prolonged lighting can partially rescue the albinic phenotypes in su mutants, implying that light may promote SlACR6-independent chloroplast development. Our results verify the role of SlACR6 in chloroplast division in tomato and uncover the tissue-specific regulation of chloroplast development.

Jianhui Nie, Qianqian Li, and Jiajing Wu contributed equally to this work.Pseudotyped viruses are useful virological tools due to their safety and versatility. Based on a VSV pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against SARS-CoV-2 in biosafety level 2 facilities. This protocol includes production, titration of the SARS-CoV-2 S pseudotyped virus and neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies, fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience of handling cells is needed before implementing this protocol.

Pseudotyped viruses are useful virological tools because of their safety and versatility. On the basis of a vesicular stomatitis virus (VSV) pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in biosafety level 2 facilities. Compared with the binding antibody test, the neutralization assay could discriminate the protective agents from the antibody family. This protocol includes production and titration of the SARS-CoV-2 S pseudotyped virus and the neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies and fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience in handling cells is needed before implementing this protocol.

The spike protein of SARS-Cov-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here we investigated 80 natural mutants and 26 glycosylation mutants for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several double mutations with D614G and another mutation in the same strains, were significantly more infectious, so was N149H, a glycosylation mutant. Most natural mutants within receptor binding domain were less infectious but some became more resistant to neutralizing antibodies. Moreover, the majority of glycosylation mutations were less infectious, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in informing our strategy for the development of vaccine and therapeutic antibodies. Funding: This work was supported by National Science and Technology Major Projects of Drug Discovery [grant number 2018ZX09101001] and National Science and Technology Major Projects of Infectious Disease [grant number 2017ZX10304402]. Conflict of Interest: All authors declare no competing interest.

The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of Spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines., Experiments with pseudotyped viruses show that the 501Y.V2 variant of SARS-CoV-2 exhibits resistance to neutralization from monoclonal antibodies and sera from convalescent as well as immunized individuals, predominantly due to the E484K and N501Y mutations in the receptor-binding domain of the viral spike protein.

Explosion of dangerous goods or a vehicle bomb can cause severe damages to bridge structures accompanied by serious casualties and significant economic losses. However, the studies on the blast risk assessment of bridges have been limited. This paper proposes a fuzzy-based framework for assessing the impact of blast incidents caused by dangerous goods on bridges. The proposed framework consists of a conversion system and aggregation process. Basic information about bridges is transformed into fuzzy numbers in the conversion system, and the risk grade is calculated by the aggregation progress. Using the proposed framework, a hierarchical structure for risk assessment of blast hazard on bridges is established, and the risk function is defined. Meanwhile, weight vectors of attributes are determined by the entropy coefficient method. The proposed framework is illustrated by evaluating the risk grade of seven bridges on a route. The attributes of the risk parameter are ranked, and the membership function of linguistic terms is calculated in the assessment process. In order to verify the rationality of the proposed framework, the risk grades of cases from other related studies are evaluated by the proposed method, and the obtained results are consistent with the previously reported results. The proposed framework can assess the risk grade of various hazards, and assessment results can be used for guiding the structural design considering the blast risk. In addition, the risk grade obtained by the proposed framework can serve as a reference for anti-explosion design.

In view of the degradation of the existing structure of the school buildings in the old city and the need to update the education model in the new period, whether to upgrade the function of the school building has become a key issue for the education department to improve the quality of teaching. In the process of renovation, there are many challenges in the design and construction of how to upgrade and renovate the school buildings with excellent historical buildings with a long history in the old city with dense buildings and public facilities. This paper takes the renovation of excellent historical buildings at No. 95 Huqiu Road, Huangpu District, Shanghai as an example. Through the description of the buildings and implementation process, it highlights the important role played by technological innovation in the upgrading and renovation of school buildings.

Casparian strip (CS) is an impregnation of endodermal cell wall, forming an apoplastic diffusion barrier which forces the symplastic and selective transport of nutrients across endodermis. This extracellular structure can be found in the roots of all higher plants and is thought to provide the protection of vascular tissues. In Arabidopsis, a genetic toolbox regulating the formation of Casparian strips has emerged recently. However, Arabidopsis has the stereotypical root which is much simpler than most other plant species. To understand the Casparian strip formation in a more complex root system, we examined CS regulatory pathways in tomato. Our results reveal a spatiotemporally conserved expression pattern of most essential components of CS machinery in tomato. Further functional analyses verify the role of homologous CS genes in the Casparian strip formation in tomato, indicating the functional conservation of CS regulatory cascade in tomato.

This study introduces a method to obtain accurate results regarding bridge seismic cost and reduce structural seismic losses. A three-span reinforced concrete (RC) continuous bridges model consistent with the reality was established, and seismic vulnerability of the RC bridge was calculated via incremental dynamic analysis combined with local earthquake disaster data. Direct losses from earthquakes are calculated based on local earthquake damage condition, specific maintenance reinforcement methods, and analysis of seismic vulnerability. The indirect economic losses caused by inspection and maintenance are calculated based on local traffic volume. To reduce the effects of bridge aging and deterioration, this paper examines periodic inspection of bridges after earthquakes. By calculating the life cycle cost of structure under different inspection frequencies, the optimal time interval was determined. The results presented for this study can serve as references for the calculation of structural seismic loss and thereby provide the basis for strategies of reducing seismic loss.

Nanowire-array nanotube-cluster bilayer TiO2 films, consisting of nanowire-array at the bottom layer and nanotube-cluster at the top layer were prepared via a two-step hydrothermal method. One step was a growth process and the other was an etching process. Etching process was used to acquire nanowire-array with a small diameter of 20–25 nm of the nanowire and nanotube-cluster. The bilayer nanostructured films were then modified with TiCl4. Villous TiO2 attached to both the inside and outside walls of the nanotube cluster was obtained only by changing the traditional concentration of TiCl4-treatment to 0.2 mol/L. The novel bilayer photoanode finally revealed a higher efficiency of 5.25% when used in dye-sensitized solar cells(DSSCs).

Plant trichomes originate from epidermal cell, forming protective structure from abiotic and biotic stresses. Different from the unicellular trichome in Arabidopsis, tomato trichomes are multicellular structure and can be classified into seven different types based on cell number, shape and the presence of glandular cells. Despite the importance of tomato trichomes in insect resistance, our understanding of the tomato trichome morphogenesis remains elusive. In this study, we quantitatively analyzed morphological traits of trichomes in tomato and further performed live imaging of cytoskeletons in stably transformed lines with actin and microtubule markers. At different developmental stages, two types of cytoskeletons exhibited distinct patterns in different trichome cells, ranging from transverse, spiral to longitudinal. This gradual transition of actin filament angle from basal to top cells could correlate with the spatial expansion mode in different cells. Further genetic screen for aberrant trichome morphology led to the discovery of a number of independent mutations in SCAR/WAVE and ARP2/3 complex, which resulted in actin bundling and distorted trichomes. Disruption of microtubules caused isotropic expansion while abolished actin filaments entirely inhibited axial extension of trichomes, indicating that microtubules and actin filaments may control distinct aspects of trichome cell expansion. Our results shed light on the roles of cytoskeletons in the formation of multicellular structure of tomato trichomes., Author summary Forming trichomes is a strategy plants have developed to defend against insects and other stresses. The function of trichomes heavily relies on their morphology, which exhibits high diversity in nature. Unicellular trichomes in Arabidopsis have been used as the model for cell morphological study. But it remains elusive how trichome shapes are established in multicullar trichomes in most plants. Using tomato, we examined multicellular trichome morphology by combining cellular biology approaches and genetic mutants. We found critical roles for of the organization of actin filaments and microtubules in forming multicellular structure of tomato trichomes.

When a fault happens to the five-level inverter, the unbalanced voltage may lead to the motor drive system collapse. A fault-tolerant control strategy based on the divided voltage modulation algorithm is proposed in this paper to keep the voltage balance and ensure the stable operation of the motor drive system under the fault condition. This modulation algorithm divides the reference voltage into two parts to achieve the independent control of each H-bridge. When an IGBT open fault (OPF) occurs in one H-bridge, it won't affect the control of other H-bridges to remove the faulty H-bridge from the inverter. This method can reduce switching loss and control the IGBT OPF fault. A design example is presented for an induction motor drive system, and simulation results validate the proposed solution.

This paper used a 3D visualization technology to realize 3 D description of underground geological environment and the well trajectory state in comprehensive logging instrument. Using VC ++ 6.0 and OPENGL graphics interface as a development platform, multilayer DEM was constructed through the Delaunay triangulations TIN generation after the linear and bilinear inserted. This model realized the real-time display, analyze and explain the strata condition, the well trajectory etc. In this system, we can observe and analysis 3 dimensional geologic body cutted from any point of view, we can also operate the whole three dimensional geologic body from any Angle.

In order to solve cost-effectively the scaling problems of pipelines in oil and gas gathering system, on the basis of analyzing the application, mechanism, influence factors of electromagnetic Dirt-remover &Dirt-proof (EDD), we designed a set of reliable and practical experiment system. This system uses the microcontroller as the main controller, which containes bridge type circuit, LED circuit and various sensors. It produces a kind of current, the polarity, amplitude and frequency of which changed rapidly to contribute to produce magnetic field rapidly changed in pipeline, which changes water molecules and water ion characteristics to achieve the purpose of anti-scaling &dirt-remover. We simulated circulating water system and tested the effect of the EDD device in the field. The experimental results indicate the EDD can restrain scaling on a certain extent and have a better anti-scaling effect.