Vaccination is the primary preventative measure against outbreaks of foot-and-mouth disease (FMD). The efficacy of inactivated FMD vaccines is mainly determined by the integrity of foot-and-mouth disease virus (FMDV) ...
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Vaccination is the primary preventative measure against outbreaks of foot-and-mouth disease (FMD). The efficacy of inactivated FMD vaccines is mainly determined by the integrity of foot-and-mouth disease virus (FMDV) particles (referred to as 146S particles), and impurities in the inactivated vaccines could result in side effects. In this study, we developed an effective affinity purification method for the purification of FMDV from cellular lysates, referred to as GEM-PA-nanotrap. To develop the GEM-PA-nanotrap, a nanobody (Nb205) against FMDV vaccine strain O/MYA98/BY/2010 146S particles was selected from a non-immunized library and fused to a peptidoglycan-binding protein anchor (PA). The PA-Nb205 fusion protein was non-covalently coupled to the surface of Gram-positive enhancer matrix (GEM) particles, which were prepared from the non-living, non-genetically modified, Gram-positive, food-grade Lactococcus lactis bacteria. The GEM-PA-nanotrap was used to purify FMDV from cellular lysates through a simple incubation and centrifugation step. The FMDV recovery rate was more than 99%, the efficiency of nonviral protein removal was about 98.3%, and the purification process had almost no effect on the integrity and immunogenicity of 146S particles. Therefore, the GEM-PA-nanotrap has potential as an effective method for the recovery and purification of FMDV during the vaccine manufacturing process. (C) 2019 Elsevier Ltd. All rights reserved.
Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on beta-amyloid (A beta) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and ir...
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Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on beta-amyloid (A beta) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)-responsive dendrimer-peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway. Moreover, this multi-target strategy exhibits a synergistic function of ROS scavenging, promoting A beta phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease A beta burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi-target treatment of AD.
In this letter, we consider blind estimation of channel parameters over a frequency-selective channel. We use a blocked Rhee-Glynn smoothing estimator to derive E-step in the expectation-maximization (EM) algorithm. T...
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In this letter, we consider blind estimation of channel parameters over a frequency-selective channel. We use a blocked Rhee-Glynn smoothing estimator to derive E-step in the expectation-maximization (EM) algorithm. The proposed algorithm copes with the curse of dimensionality of a forward- backward algorithm;meanwhile, it is easy to parallelize, which is amenable to a modern computing hardware and speeds up the estimation of channel parameters. The experiment results show that the proposed algorithm is close to the Baum-Welch algorithm in terms of convergence of channel coefficients and outperforms the EM algorithm coupled with a joined two-filter smoothing algorithm in terms of convergence of channel coefficients and running time.
Natural and synthetic progestins in receiving streams can disrupt the normal endocrine systems of fish. Norethindrone (NET) is a widely used synthetic progestin that often appears in wastewater effluents. For this res...
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Natural and synthetic progestins in receiving streams can disrupt the normal endocrine systems of fish. Norethindrone (NET) is a widely used synthetic progestin that often appears in wastewater effluents. For this research, adult female western mosquitofish (Gambusia affinis) were exposed to NET at three concentrations. The effects of NET on the following biological factors were evaluated: the histology of the ovaries and livers, the anal fin morphology, and transcription of genes related to steroidogenesis signaling pathways in the livers. After 42 d exposure to NET at 33.0 ng L-1 and 347.5 ng L-1, rapid masculinization, an increase in the number of atretic and postovulatory follicles in the ovary, enhanced vascularization, degenerated hepatocytes and irregular nuclei in the livers were observed. Exposure to NET did not affect the expression of the androgenic and estrogenic receptor genes and Cyp19a except for a significant up-regulation of Er alpha. However, the expression of Vtg A, Vtg B, and Vtg C were markedly inhibited in the females exposed to three concentrations of NET. Compared to the control female, exposure to NET at 33.0 ng L-1 and 347.5 ng L-1 caused a 4.4- and 5.8-fold increase in the expression of Hsd17 beta 3 in the livers, respectively. The results demonstrate that NET can cause rapid masculinization of female G. affinis, hepatopathological alterations and inhibited expressions of Vtg A, Vtg B, and Vtg C. The results imply that G. affinis populations might be threatened in NET-contaminated environment. (C) 2018 Elsevier Ltd. All rights reserved.
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