The Epitope and Neutralization Mechanism of AVFluIgG01, a Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus

The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus

Prevalence of Hepatitis E Virus in Swine Fed on Kitchen Residue

The aim of this study was to investigate the prevalence of swine hepatitis E virus (HEV) in pigs fed different feedstuffs (kitchen residue or mixed feeds) and genetic identification of HEV isolated in Hebei province, China. Serum and fecal samples were collected from adult swine. Anti-HEV antibody was evaluated by double sandwich antigen enzyme immunoassay. HEV RNA was extracted from fecal samples and amplified by nested RT-PCR. The reaction products were sequenced, and the sequence analyzed. Virus-like particles were distinguishable by negative staining in the electron microscope. Histopathological observation and immunohistochemical localization were used in the animal models. Overall, the anti-HEV positive percentage of serum samples from pigs fed on kitchen residue was 87.10% (27/31), and 53.06% (130/245) from pigs fed on complete feed. The HEV RNA positivity rate of fecal samples from pigs fed on kitchen residue was 61.54% (8/13), but zero for pigs fed on complete feed. Sequence analysis of these eight samples and comparison with the published sequence showed that there were eight groups that belonged to genotype 4 d and the nucleotide identity was 95.6–99.3%. swHE11 is most closely related to strain CCC220, and the other seven HEV isolates were most closely related to strains swGX40, SwCH189 and V0008ORF3, which are isolates from human and pigs. Histopathological observation showed that there was liver damage in the experimental group, and immunohistochemistry indicated that the HEV antigens were strongly positive at 7 days after infection. The results demonstrated that the prevalence of HEV in pigs fed on kitchen residue was higher than in those fed on complete feed (P<0.05)

Coordination number of the packing of ternary mixtures of spheres : DEM simulations versus measurements

Coordination number is an important microscopic parameter in describing the packing of particles. However, little information is available for particle mixtures because of the difficulty of investigating them experimentally. This article presents a numerical study on the coordination numbers of a ternary packing system with size ratios of 24.4/11.6/6.4 by means of the discrete element method (DEM). Good agreement between the simulated and measured results was obtained, which confirms, at a particle scale, that DEM is capable of generating reliable results for structural analysis of particle packing. It was also found that the coordination number distribution of each of the cases considered can be described by the so-called Johnson SB function. The distribution parameters of the function were quantified based on the DEM simulation results so that the coordination number distributions corresponding to different contact types in this ternary packing system can be fully described

Radical tessellation of the packing of ternary mixtures of spheres

The packing of ternary mixtures of spheres with size ratios 24.4/11.6/6.4 is simulated by means of the discrete element method. The packing structure is analyzed by the so called radical tessellation which is an extension of the well-established Voronoi tessellation. The topological and metric properties of radical polyhedra are quantified as a function of the volume fractions of this ternary packing system. These properties include the number of edges, area and perimeter per radical polyhedron face, and the number of faces, surface area and volume per radical polyhedron. The properties of each component of a mixture are shown to be strongly dependent on the volume fractions. Their average values can be quantified by a cubic polynomial equation. The results should be useful for understanding the packing structures of multi-sized particles

Radical tessellation of the packing of spheres with a log-normal size distribution

The packing of particles with a log-normal size distribution is studied by means of the discrete element method. The packing structures are analyzed in terms of the topological properties such as the number of faces per radical polyhedron and the number of edges per face, and the metric properties such as the perimeter and area per face and the perimeter, area, and volume per radical polyhedron, obtained from the radical tessellation. The effect of the geometric standard deviation in the log-normal distribution on these properties is quantified. It is shown that when the size distribution gets wider, the packing becomes denser; thus the radical tessellation of a particle has decreased topological and metric properties. The quantitative relationships obtained should be useful in the modeling and analysis of structural properties such as effective thermal conductivity and permeability

An assessment of the mathematical models for estimating the coordination number of the packing of multisized particles

Coordination number (CN) is an important microscopic parameter in describing the packing of particles. There are a few mathematical models proposed in the literature to calculate the CN of a particle mixture. However, they have not been comprehensively assessed as the experimental data are limited. In this paper, the applicability of three models, respectively proposed by Dodds, Ouchiyama & Tanaka, and Suzuki & Oshima, is assessed against the results recently generated by means of discrete element method. The results indicate that the model of Ouchiyama & Tanaka differ from the simulated CNs significantly, thus not recommended. The other two models produce similar results, but the Dodds model is probably more reasonable. In particular, these two models are able to estimate the variation trend of the average CN for various particle size distributions but their predictability reduces with the increase of particle size difference. The Dodds model becomes numerically unsolvable when the small-to-large size ratio is smaller than 0.154. Therefore, modification of the existing models or development of a new model is required in future studies for better prediction of the CN of the packings of multisized particles

PAC spectroscopy of electronic ceramics

Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen