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L-HBsAg is a third-generation hepatitis vaccine capable of inducing antibodies in non-responders and thus providing potentially therapeutic treatment. In this study, L-HBsAg was administered using microneedles (MN) without an adjuvant to induce intradermal (ID) immunization, and the efficacy of ID immunization was compared with that of intramuscular (IM) immunization that uses a conventional formulation with an adjuvant of aluminum hydroxide (L-HBsAg-AL-IM). The L-HBsAg was dip-coated onto 800-μm-long microneedles made of polylactic acid (PLA). Delivery efficiency and administration time were determined through in vitro experiments using porcine skin. The denaturation of the formulation against sterilization by gamma rays was observed. A storage test and a freeze-thaw cycle test of the microneedles with trehalose as a stabilizer (L-HBsAg-MN-Tre) were observed. An antibody titer of L-HBsAg-MN-Tre was compared with that of the conventional IM immunization of the L-HBsAg solution with aluminum hydroxide (L-HBsAg-AL-IM). The formulation containing L-HBsAg was located on the upper third of the microneedle tips. The formulation on the MN was dissolved and delivered within 30 min of insertion into porcine skin in vitro. Trehalose was selected as a stabilizer, and the stabilizing effect increased with the increase of trehalose content in the solidified formulation. L-HBsAg-MN with 15% of trehalose was stable for 7 days at 40 °C and showed increased stability compared to the conventional liquid formulations. L-HBsAg-MN-Tre showed improved stability during the freeze-thaw cycle. The antibody titer of L-HBsAg-MN-Tre at 28 days was higher than that of L-HBsAg-AL-IM. ID administration of L-HBsAg-MN-Tre showed better efficacy and improved thermal and freeze thaw stability compared to L-HBsAg-AL-IM. Therefore, L-HBsAg-MN-Tre administration showed the possibility of ID delivery of L-HBsAg without the use of an adjuvant for the efficacy, convenience, and safety of pediatric vaccination.

Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein-only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S-subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild-type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines., Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and has a high mortality of ∼34%. However, since its discovery in 2012, an effective vaccine has not been developed for it. To develop a vaccine against multiple strains of MERS-CoV, we targeted spike glycoprotein (S) using prime-boost vaccination with DNA and insect cell-expressed recombinant proteins for the receptor-binding domain (RBD), S1, S2, SΔTM, or SΔER. Our S subunits were generated using an S sequence derived from the MERS-CoV EMC/2012 strain. We examined humoral and cellular immune responses of various combinations with DNA plasmids and recombinant proteins in mice. Mouse sera immunized with SΔER DNA priming/SΔTM protein boosting showed cross-neutralization against 15 variants of S-pseudovirions and the wild-type KOR/KNIH/002 strain. In addition, these immunizations provided full protection against the KOR/KNIH/002 strain challenge in human DPP4 knock-in mice. These findings suggest that vaccination with the S subunits derived from one viral strain can provide cross-protection against variant MERS-CoV strains with mutations in S. DNA priming/protein boosting increased gamma interferon production, while protein-alone immunization did not. The RBD subunit alone was insufficient to induce neutralizing antibodies, suggesting the importance of structural conformation. In conclusion, heterologous DNA priming with protein boosting is an effective way to induce both neutralizing antibodies and cell-mediated immune responses for MERS-CoV vaccine development. This study suggests a strategy for selecting a suitable platform for developing vaccines against MERS-CoV or other emerging coronaviruses. IMPORTANCE Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein-only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S-subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild-type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines.

In this study, dissolving microneedles (DMNs) with dual-release pattern, capable of both bolus release and slow release, were prepared. These DMNs were used with a hepatitis B vaccine that requires multiple shots to achieve immunological efficacy comparable to that obtained when two separate shots are administered. Dissolving microneedles with HBsAg in PLA tips and CMC coating formulation together (HBsAg-PLA/CMC-DMNs) consist of polylactic acid (PLA) tips for slow release, a carboxy-methyl cellulose (CMC) coating formulation for bolus release, and a dissolving base of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) for dissolution in the skin. The in vitro release pattern of HBsAg from the CMC coating formulation and PLA tips was observed. Through an in vivo test, 1) the delivery efficiency of HBsAg-PLA/CMC-DMNs was observed, and 2) the immunological efficacy of this method was compared with the efficacy of two shots delivered by conventional intramuscular (IM) administration and two shots delivered by HBsAg-coated microneedle (CMNs) administration. HBsAg-PLA/CMC-DMNs punctured the skin successfully. The PVA/PVP base was completely dissolved within 10 min of insertion, resulting in the delivery of all microneedle tips into the skin. In the in vitro release experiment, all of the HBsAg in the CMC coating formulation was released within 20 min, and the HBsAg present in the PLA tips was gradually released over more than 55 days. The antibody titer of one shot of HBsAg-PLA/CMC-DMNs was the same as or higher than two shots delivered by conventional IM and CMN methods. DMNs with dual-release pattern can deliver two formulations simultaneously with a single shot, resulting in improved immunological efficacy of HBsAg that requires multiple doses. In addition, this dual-release MN system can be used for the delivery of other drugs that require multiple administrations.

The implementation of technological developments in the field of Information and Communication Technologies (ICT) have been carried out by many countries to help make government service delivery to their citizens better. E-government initiatives are developed to try and attain a higher level of efficacy in government service provision by utilizing the latest developments in ICTs to innovate and promote the interactions with citizens. E-government initiatives should not only be about putting forms, websites and services online, but should also provide a framework of options on how the government continues to improve their services and how to bring adjustments based on the users' demand. A citizen-centric study of how citizens perceive e-government services should help governments and future researchers adjust their initiatives accordingly. This study explores the citizens' perception of e-government in Korea by utilizing an Importance-Performance Analysis method and also seeks to identify which attributes of e-government can influence citizens' satisfaction and behavioral intentions. The result of the IPA indicates that technical support/feedback and real-time service provision are the main areas where e-government should focus on. Overall, the IPA model indicates other factors that can influence satisfaction and behavioral intention, and a well-structured e-government plan based on the findings may as well enhance the specific aspect of e-government.

The structural aspects of LaAlO 3 /SrTiO 3 heterostructure were investigated in detail to explain the electronic properties of interface. Cell volume change, atomic displacements were calculated for the (1×1) LaAlO 3 (m unit cells, m=3, 5)/SrTiO 3 (4 unit cells) system using ab-initio method. Both of LaAlO 3 and SrTiO 3 cells were stretched in longitudinal directions. The oxygen atoms in the cells moved to n-type interface and the movement, consequently, could be interred to contribute the conductivity of n-type interface.

Energy storage system(ESS) is operated to save and release electric energy. And the battery in an ESS performs an essential function. For this purpose its capacity needs to be finely optimized for specific applications(peak shaving, frequency control, arbitrage, UPS etc). Some papers have already showed the studies about the topic of optimization of battery capacity in an ESS, but a battery degradation factor and irregular operation event have not much been considered. Actually, ESS may experience a very irregular operational event and the decrease of battery capacity during repeated charge/discharge is a major issue to be addressed. In the ESS industry, usually several factors such as state of charge, time, temperature, and C-rate interdependently affect the decrease of battery capacity in a complicated mode. In order to install the ESS in a specific application looking for a reasonable benefit and a sufficent realiability, ESS lifetime prediction technique considering degradation of battery is highly required. In this study, the battery capacity fading through test of dynamic stress factors was quantifized and reflected to designing of ESS battery. The goal is to make an accurate estimating methodology of ESS lifetime and benefit from its installation in specific applications.

Using ab initio calculations, we studied structural characteristics of LaAlO3/SrTiO3 interface and related with its extraordinarily increased electric conductivity. In both of the two (LaAlO3) m /SrTiO3 heterojunction models (m = 3, 5), the oxygen atoms in the cells were displaced toward the n-type interface and the Ti-centered octahedron structure was compressed along the [001] direction by the atomic reconstructions at the (LaAlO3) m /(SrTiO3)4 interfaces. As a result, the 3d x y orbital of the Ti atom was preferentially occupied due to the lowered energy state of the 3d x y orbital, which arises from the crystal field asymmetry. We reason that the extra electrons occupy the 3d x y orbital are accumulated at the interface by the displacement of the oxygen atoms. This accumulation contributes to the conductivity of the n-type interface.