Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 mg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 mg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60 % in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination agains

From non-market support to cost-competitive incentives: Wind energy commercialization in China

This paper presents an overview of the development of wind energy in China. By examining the economics of windfarm development, it compares the economics of wind technology with other conventional energy technologies and analyzes the role of alternative policy instruments. Meanwhile, it identifies the major constraints of wind technology development and the defects of current non-market support from the government. It shows that the development of wind power will be directly subject to rational policy change, incentive mechanisms and institutional framework building. Particular importance is paid to market incentives to reach the objectives of commercialization and industrialization of wind power. The paper recommends some cost-competitive incentive measures and policies to drive the wind power market. It concludes that promising market incentives to speed up the development of wind energy include: (i) establish market competition mechanisms through standard power purchase agreement; (ii) adjust tax policies and government subsidies; (iii) stimulate investment incentive policies and regulations; and (iv) change governmental institutions and management modes

Large modulation capacity in graphene-based slot modulators by enhanced hybrid plasmonic effects

© 2018, The Author(s). We present an effective scheme to improve the modulation capacity in graphene-based silicon modulator by employing the double slots configuration with hybrid plasmonic effects. Two modulators, i.e., metal-insulator-metal and insulator-metal-insulator configurations have been demonstrated, showing that the double slots design can significantly improve the modulation efficiency. The obtained modulation efficiency is up to 0.525 dB/μm per graphene layer, far exceeding previous studies. It can be found that the light-graphene interaction plays a pivotal role in the modulation efficiency, whereas the height of metal has profound influence on the modulation. Our results may promote various future modulation devices based on graphene

Large modulation capacity in graphene-based slot modulators by enhanced hybrid plasmonic effects

Abstract We present an effective scheme to improve the modulation capacity in graphene-based silicon modulator by employing the double slots configuration with hybrid plasmonic effects. Two modulators, i.e., metal-insulator-metal and insulator-metal-insulator configurations have been demonstrated, showing that the double slots design can significantly improve the modulation efficiency. The obtained modulation efficiency is up to 0.525 dB/μm per graphene layer, far exceeding previous studies. It can be found that the light-graphene interaction plays a pivotal role in the modulation efficiency, whereas the height of metal has profound influence on the modulation. Our results may promote various future modulation devices based on graphene

Large modulation capacity in graphene-based slot modulators by enhanced hybrid plasmonic effects

© 2018, The Author(s). We present an effective scheme to improve the modulation capacity in graphene-based silicon modulator by employing the double slots configuration with hybrid plasmonic effects. Two modulators, i.e., metal-insulator-metal and insulator-metal-insulator configurations have been demonstrated, showing that the double slots design can significantly improve the modulation efficiency. The obtained modulation efficiency is up to 0.525 dB/μm per graphene layer, far exceeding previous studies. It can be found that the light-graphene interaction plays a pivotal role in the modulation efficiency, whereas the height of metal has profound influence on the modulation. Our results may promote various future modulation devices based on graphene

Validation of the JEN frailty index in the National Long-Term Care Survey community population: identifying functionally impaired older adults from claims data

Abstract Background Use of a claims-based index to identify persons with physical function impairment and at risk for long-term institutionalization would facilitate population health and comparative effectiveness research. The JEN Frailty Index [JFI] is comprised of diagnosis domains representing impairments and multimorbid clusters with high long-term institutionalization [LTI] risk. We test the index’s discrimination of activities-of-daily-living [ADL] dependency and 1-year LTI and mortality in a nationally representative sample of over 12,000 Medicare beneficiaries, and compare long-term community survival stratified by ADL and JFI. Methods 2004 U.S. National Long-Term Care Survey data were linked to Medicare, Minimum Data Set, Veterans Health Administration files and vital statistics. ADL dependencies, JFI score, age and sex were measured at baseline survey. ADL and JFI groups were cross-tabulated generating likelihood ratios and classification statistics. Logistic regression compared discrimination (areas under receiver operating characteristic curves), multivariable calibration and accuracy of the JFI and, separately, ADLs, in predicting 1-year outcomes. Hall-Wellner bands facilitated contrasts of JFI- and ADL-stratified 5-year community survival. Results Likelihood ratios rose evenly across JFI risk categories. Areas under the curves of functional dependency at ≥3 and ≥ 2 for JFI, age and sex models were 0.807 [95% c.i.: 0.795, 0.819] and 0.812 [0.801, 0.822], respectively. The area under the LTI curve for JFI and age (0.781 [0.747, 0.815]) discriminated less well than the ADL-based model (0.829 [0.799, 0.860]). Community survival separated by JFI strata was comparable to ADL strata. Conclusions The JEN Frailty Index with demographic covariates is a valid claims-based measure of concurrent activities-of-daily-living impairments and future long-term institutionalization risk in older populations lacking functional information

Large-Scale Synthesis of Silver Nanoparticles by Aqueous Reduction for Low-Temperature Sintering Bonding

Silver nanoparticles with average diameter of 22.4 nm were prepared by aqueous reduction method for low-temperature sintering bonding application. The reaction temperature and PVP concentration, which are the influential factors of nanoparticle characteristics, were investigated during reduction process. In our research, monodispersity of nanoparticles was remarkably improved while unfavorable agglomeration was avoided with the AgNO3/PVP mass ratio of 1 : 4 at the reaction temperature 30°C. Besides, copper pads were successfully bonded using sintering paste employing fresh silver nanoparticles with diameter of 20~35 nm at 200°C. In addition, after morphology of the bonding joint was analysed by scanning electron microscope (SEM), the porous sintering characteristics were confirmed

miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection

Fibroblast growth factor 2 (FGF2 or basic FGF) regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV)-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194) expression is significantly decreased in A549 alveolar epithelial cells (AECs) following infection with IAV/Beijing/501/2009 (BJ501). We found that miR-194 can directly target FGF2, a novel antiviral regulator, to suppress FGF2 expression at the mRNA and protein levels. Overexpression of miR-194 facilitated IAV replication by negatively regulating type I interferon (IFN) production, whereas reintroduction of FGF2 abrogated the miR-194-induced effects on IAV replication. Conversely, inhibition of miR-194 alleviated IAV-induced lung injury by promoting type I IFN antiviral activities in vivo. Importantly, FGF2 activated the retinoic acid-inducible gene I signaling pathway, whereas miR-194 suppressed the phosphorylation of tank binding kinase 1 and IFN regulatory factor 3. Our findings suggest that the miR-194-FGF2 axis plays a vital role in IAV-induced lung injury, and miR-194 antagonism might be a potential therapeutic target during IAV infection

Intradermal delivery of a fractional dose of influenza H7N9 split vaccine elicits protective immunity in mice and rats

Vaccination is the most effective method of preventing the spread of the influenza virus. However, the traditional intramuscular (IM) immunization causes fear, pain, and cross infection. In contrast, needle-free (NF) immunization is quick and easy for medical personnel and painless and safe for patients. In this study, we assessed the safety and protective efficacy of NF intradermal (ID) immunization with the influenza H7N9 split vaccine (Anhui H7N9/PR8). A preliminary safety evaluation showed that ID immunization with 15 μg of the H7N9 influenza vaccine was not toxic in rats. Moreover, the antigen was metabolized more rapidly after ID than after IM immunization, as determined by in vivo imaging, and ID immunization accelerated the generation of a specific immune response. Additionally, ID immunization with a 20% dose of the H7N9 split vaccine Anhui H7N9/PR8 offered complete protection against lethal challenge by the live H7N9 virus. Taken together, our findings suggest that NF ID immunization with the H7N9 influenza vaccine induces effective protection, has a good safety profile, requires little antigen, and elicits an immune response more rapidly than does IM immunization. This approach may be used to improve the control of influenza H7N9 outbreaks