Broad cross-protection by recombinant influenza viruses expressing conserved M2e- hemagglutinin chimera and virus-like particles in young and aged mice

Chapter1: Broad cross-protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin. The objective of project 1 was to determine whether intranasal immunization with live recombinant H3N2 virus expressing chimeric 4xM2e-HA would induce broadly cross-protective immunity against different subtypes of influenza A viruses in a mouse model. In recent years, antigenic drifts have severely limited the effectiveness of the H3N2 component of seasonal influenza vaccines. Here, using the reverse genetic (rg) technique, we generated reassortant seasonal influenza rgH3N2 4xM2e virus containing chimeric 4xM2e-HA in which the HA and NA genes were derived from A/Switzerland/9715293/2013 (H3N2) and the remaining 6 genes from the A/PR8 backbone. Reassortant rgH3N2 4xM2e virus containing chimeric 4xM2e-HA was found to retain comparable growth properties but displayed highly attenuated phenotypes in mice. Cross-protective efficacy against different subtypes (H1N1, H3N2, H5N1, H7N9, H9N2) of influenza A virus was tested in intranasally immunized BALB/c mice with rgH3N2 4xM2e. This study implicates a strategy of improving cross-protection by utilizing currently licensed recombinant influenza vaccine platforms. Chapter2: Enhanced cross-protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes. The goal of project 2 was to test whether a strategy of hetero prime-boost vaccination with recombinant influenza viruses expressing chimeric 4xM2e-HA would induce more effective cross-protection than homologous prime-boost vaccination. The impact of heterosubtypic vaccination with recombinant 4xM2e-HA influenza virus vaccines and pre-existing immunity on cross-protection against influenza viruses remains unknown. In this study, I investigated the efficacy of cross-protection by heterosubtypic prime- boost vaccination with live recombinant 4xM2e-HA H1N1 and H3N2 influenza virus vaccines in C57BL/6 mice known to be a low responder to immune-subdominant conserved epitopes. The experimental outcomes of project 2 demonstrated that hetero prime-boost strategies using recombinant 4xM2e-HA influenza virus vaccination induced more effective cross-protection against antigenically different viruses than homologous repeat vaccination in C57BL/6 mice. The roles of M2e and stalk immunity in conferring cross-protection were explored and discussed in this study. Chapter 3: Hemagglutinin virus-like particle is immunogenic and provides heterologous protection against influenza virus in young adult and aged mice. The goal of project 3 was to investigate immune responses and homo and cross-protective efficacy in aged mice after vaccination with a platform of virus-like particles (VLP) presenting H1 HA with and without molecularly anchored cytokine adjuvants incorporated, in comparison with those in young adult mice. Vaccine effectiveness is inferior in the aged population at high risk of severe illness from influenza virus infection. For the elderly, safe and highly immunogenic vaccines need to be developed. In project 3, host immune responses and homo and cross-protective efficacy was determined, after vaccination with a VLP vaccine platform which expresses H1 HA from A/PR8/34 (PR8 HA VLP) in young adults and aged (18-month-old) BALB/c mice. In addition, I investigated the adjuvant impact of cytokines (GM-CSF and IL-12) engineered to be incorporated into HA VLP vaccines on inducing IgG antibodies, hemagglutination inhibition titers, and homo and hetero protection in aged mice, compared to those in young adult mice. Higher doses of vaccination with H1 HA VLP and cytokines incorporated onto H1 HA VLP were found to be more effective in inducing protective immunity against homo and hetero viruses in aged mice

Cosmological constraints from the redshift dependence of the Alcock-Paczynski effect: Dynamical dark energy

We perform an anisotropic clustering analysis of 1,133,326 galaxies from the Sloan Digital Sky Survey (SDSS-III) Baryon Oscillation Spectroscopic Survey (BOSS) Data Release (DR) 12 covering the redshift range $0.15<z<0.69$. The geometrical distortions of the galaxy positions, caused by incorrect cosmological model assumptions, are captured in the anisotropic two-point correlation function on scales 6 -- 40 $h^{-1}\rm Mpc$. The redshift evolution of this anisotropic clustering is used to place constraints on the cosmological parameters. We improve the methodology of Li et al. 2016, to enable efficient exploration of high dimensional cosmological parameter spaces, and apply it to the Chevallier-Polarski-Linder parametrization of dark energy, $w=w_0+w_a{z}/({1+z})$. In combination with the CMB, BAO, SNIa and $H_0$ from Cepheid data, we obtain $\Omega_m = 0.301 \pm 0.008,\ w_0 = -1.042 \pm 0.067,\ $and$w_a = -0.07 \pm 0.29$(68.3\% CL). Adding our new AP measurements to the aforementioned results reduces the error bars by$\sim$30 -- 40\% and improves the dark energy figure of merit by a factor of$\sim$2. We check the robustness of the results using realistic mock galaxy catalogues.Comment: 12 pages, 9 figures, accepted to Ap

Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia

The Effect Of Corporate Governance On Unfaithful Disclosure Designation And Unfaithful Disclosure Penalty Points

This paper investigates the relation between Unfaithful Disclosure Corporations (“UDC”) and corporate governance using listed firm (KOSPI and KOSDAQ) data in Korea. Prior literature reports that corporate governance has an impact on the level of disclosure and the quality of disclosure provided by companies. However, it is hard to find the studies about corporate governance and UDC at the term of disclosure quality. Compare to some financially advanced countries, Korea established corporate governance in a relatively short period of time; hence concerns have been raised the corporate governance have not played effective role to monitor management. We question how corporate governance affects companies’ unfaithful disclosure by using several corporate governance proxy variables and UDC data which is unique system in Korea. From the empirical tests, we find a negative association between the proportion of outside directors, an indicator of the board’s independence, and UDC designation, among companies listed on both KOSPI and KOSDAQ. On the other hand, there is a significant positive association between the proportion of outside directors and UDCs’ imposed and accumulated penalty points among KOSDAQ-listed companies. This implies that outside director system effectively play a monitoring role however due to different natures of members included in outside directors, the system often fails to control regarding based reasons for penalty points imposition. In addition, we find the percentage of foreign equity ownership showed statistically significant positive association with UDC designation and a significant positive association with the imposed and accumulated penalty points among KOSPI-listed companies. We interpret this results that foreign investors with a short-term investment propensity may not enough to play a proper monitoring role in Korea and thereby they cannot effectively control the disclosure quality provided by the management. We also find that there is a significant positive association between the percentage of managerial ownership and UDC designation in the KOSDAQ market. &nbsp; This study will contribute to academics and disclosure-related practitioners by documenting about corporate governance and its impact on unfaithful disclosure corporations

Lymphangiography to treat postoperative lymphatic leakage: a technical review.

In addition to imaging the lymphatics and detecting various types of lymphatic leakage, lymphangiography is a therapeutic option for patients with chylothorax, chylous ascites, and lymphatic fistula. Percutaneous thoracic duct embolization, transabdominal catheterization of the cisterna chyli or thoracic duct, and subsequent embolization of the thoracic duct is an alternative to surgical ligation of the thoracic duct. In this pictorial review, we present the detailed technique, clinical applications, and complications of lymphangiography and thoracic duct embolization

Improved Noisy Student Training for Automatic Speech Recognition

Recently, a semi-supervised learning method known as "noisy student training" has been shown to improve image classification performance of deep networks significantly. Noisy student training is an iterative self-training method that leverages augmentation to improve network performance. In this work, we adapt and improve noisy student training for automatic speech recognition, employing (adaptive) SpecAugment as the augmentation method. We find effective methods to filter, balance and augment the data generated in between self-training iterations. By doing so, we are able to obtain word error rates (WERs) 4.2%/8.6% on the clean/noisy LibriSpeech test sets by only using the clean 100h subset of LibriSpeech as the supervised set and the rest (860h) as the unlabeled set. Furthermore, we are able to achieve WERs 1.7%/3.4% on the clean/noisy LibriSpeech test sets by using the unlab-60k subset of LibriLight as the unlabeled set for LibriSpeech 960h. We are thus able to improve upon the previous state-of-the-art clean/noisy test WERs achieved on LibriSpeech 100h (4.74%/12.20%) and LibriSpeech (1.9%/4.1%).Comment: 5 pages, 5 figures, 4 tables; v2: minor revisions, reference adde

Intrinsic Image Popularity Assessment

The goal of research in automatic image popularity assessment (IPA) is to develop computational models that can accurately predict the potential of a social image to go viral on the Internet. Here, we aim to single out the contribution of visual content to image popularity, i.e., intrinsic image popularity. Specifically, we first describe a probabilistic method to generate massive popularity-discriminable image pairs, based on which the first large-scale image database for intrinsic IPA (I$^2$PA) is established. We then develop computational models for I$^2$PA based on deep neural networks, optimizing for ranking consistency with millions of popularity-discriminable image pairs. Experiments on Instagram and other social platforms demonstrate that the optimized model performs favorably against existing methods, exhibits reasonable generalizability on different databases, and even surpasses human-level performance on Instagram. In addition, we conduct a psychophysical experiment to analyze various aspects of human behavior in I$^2$PA.Comment: Accepted by ACM Multimedia 201