Viremia Associated with Fatal Outcomes in Ferrets Infected with Avian H5N1 Influenza Virus

Avian H5N1 influenza viruses cause severe disease and high mortality in infected humans. However, tissue tropism and underlying pathogenesis of H5N1 virus infection in humans needs further investigation. The objective of this work was to study viremia, tissue tropism and disease pathogenesis of H5N1 virus infection in the susceptible ferret animal model. To evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the H5N1 strain A/VN/1203/04 to assess clinical signs after infection and virus load in lung, brain, ileum, nasal turbinate, nasal wash, and blood. We observed that H5N1 infection in ferrets is characterized by high virus load in the brain and and low levels in the ileum using real-time PCR. In addition, viral RNA was frequently detected in blood one or two days before death and associated with symptoms of diarrhea. Our observations further substantiate pathogenicity of H5N1 and further indicate that viremia may be a bio-marker for fatal outcomes in H5N1 infection

Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4

BACKGROUND: Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenes in vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of specific cell types. Our goal was to specifically target cells that express the T cell tropic HIV-1 envelope protein (Env) using the highly specific interaction of Env with its cellular receptor (CD4) inserted into the envelope of an HIV-1-based viral vector. RESULTS: To generate HIV-1-based vectors carrying the CD4 molecule in their envelope, the CD4 ectodomain was fused to diverse membrane anchors and inserted together with the HIV-1 coreceptor CXCR4 into the envelopes of HIV-1 vector particles. Independent of the type of CD4 anchor, all chimeric CD4 proteins inserted into HIV-1 vector envelopes and the resultant HIV(CD4/CXCR4) particles were able to selectively confer neomycin resistance to cells expressing the fusogenic T cell tropic HIV-1 Env protein. Unexpectedly, in the absence of Env on the target cells, all vector particles carrying the CD4 ectodomain anchored in their envelope adhered to various cell types without infecting these cells. This cell adhesion was very avid. It was independent of the presence of Env on the target cell, the type of CD4 anchor or the presence of CXCR4 on the particle. In mixed cell populations with defined ratios of Env(+)/Env(- )cells, the targeted transduction of Env(+ )cells by HIV(CD4/CXCR4) particles was diminished in proportion to the number of Env(- )cells. CONCLUSION: Vector diversion caused by a strong, non-selective cell binding of CD4(+)-vector particles effectively prevents the targeted transduction of HIV-1 Env expressing cells in mixed cell populations. This Env-independent cell adhesion severely limits the effective use of targeted HIV(CD4/CXCR4) vectors designed to interfere with HIV-1 replication in vivo. Importantly, the existence of this newly described and remarkably strong CD4-dependent cell adhesion suggests that the multiple viral efforts to reduce CD4 cell surface expression may, in part, be to prevent cell adhesion to non-target cells and thereby to increase the infectivity of viral progeny. Preventing CD4 down-modulation by HIV-1 might be an effective component of a multi-faceted antiviral strategy

Delving into Crispness: Guided Label Refinement for Crisp Edge Detection

Learning-based edge detection usually suffers from predicting thick edges. Through extensive quantitative study with a new edge crispness measure, we find that noisy human-labeled edges are the main cause of thick predictions. Based on this observation, we advocate that more attention should be paid on label quality than on model design to achieve crisp edge detection. To this end, we propose an effective Canny-guided refinement of human-labeled edges whose result can be used to train crisp edge detectors. Essentially, it seeks for a subset of over-detected Canny edges that best align human labels. We show that several existing edge detectors can be turned into a crisp edge detector through training on our refined edge maps. Experiments demonstrate that deep models trained with refined edges achieve significant performance boost of crispness from 17.4% to 30.6%. With the PiDiNet backbone, our method improves ODS and OIS by 12.2% and 12.6% on the Multicue dataset, respectively, without relying on non-maximal suppression. We further conduct experiments and show the superiority of our crisp edge detection for optical flow estimation and image segmentation.Comment: Accepted by TI

Influence of mixed-phase TiO2 on the activity of adsorption-plasma photocatalysis for total oxidation of toluene

Herein, the effects of different crystalline phases of TiO2 on the adsorption-plasma photocatalytic oxidation of toluene were investigated. First, photocatalysts loaded on a molecular sieve (MS) were characterised and the catalytic performance of toluene abatement was evaluated in a plasma system. The COx yield of the pure anatase (An) sample outperformed other samples in the adsorption-plasma photocatalytic oxidation process, especially for CO2 yield (69.1%). It was revealed that the highest space-time-yield of 2.35 gco(2)/Lcat.h was also achieved using plasma-An/MS. However, the highest total toluene abatement (99.5%) was achieved in the plasma-P25/MS system. The plasma-generated UV flux only played a minor role in photocatalyst activation because of the very low UV flux of 2.7 mu W/cm(2) generated by discharge. For the degradation pathway, compared with the plasma-MS system, byproducts of 1,3-Butadiyne (C4H2), guanidine, methyl-(C2H7N3) did not exist in the TiO2-assisted system, indicating a difference in the toluene degradation pathway. There were no obvious effects of different TiO2 samples on organic byproducts generation, and almost a complete mineralisation of all byproducts was observed after 30 min of treatment, with the exception of ethylamine (C2H7N) and acetaldehyde (C2H4O). Finally, a cycled adsorption-plasma study was conducted to reveal the sustainability of the process. A partial deactivation of plasma-An/MS with less than 7% decrease in CO2 selectivity after 7 cycles was revealed, which is a promising result for use in possible industrial applications

Application of the New Generation of Sequencing Technologies for Evaluation of Genetic Consistency of Influenza A Vaccine Viruses

For almost half a century, Sanger sequencing has been the conventional method for sequencing DNA. However, its utility for sequencing heterogeneous viral populations is limited because it can only detect mutations that are present in a significant portion of the DNA molecules. Several molecular methods that quantify mutations present at low levels in viral populations were proposed for evaluation of genetic consistency of viral vaccines; however, these methods are only suitable for single site polymorphisms, and cannot be used to screen for unknown mutations

Phased Geometric Controls of V-Shaped Three-Level System for Zero-field Quantum Sensing

Here we propose and demonstrate a phased geometric control protocol for zero-field double quantum gates in a V-shaped three-level spin system. This method utilizes linearly polarized microwave pulses and exploits the geometric qubit properties to prevent state leakage. By employing specific phased geometric controls, we realize a low-power multi-pulse zero-field sensing technique using single nitrogen-vacancy centers in diamond. Our method offers a novel approach to implement precise double quantum gate operations with an adaptable driving power, making it a valuable tool for zero-field spin-based quantum technology