Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

Kim, M.C.,Lee, J.S.,Kwon, Y.M.,O, E.,Lee, Y.J.,Choi, J.G.,Wang, B.Z.,Compans, R.W.,Kang, S.M. Elsevier/North-Holland 2013 Antiviral research Vol.99 No.3

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection

Kim, M.C.,Lee, J.W.,Choi, H.J.,Lee, Y.N.,Hwang, H.S.,Lee, J.,Kim, C.,Lee, J.S.,Montemagno, C.,Prausnitz, M.R.,Kang, S.M. Elsevier Science Publishers 2015 Journal of controlled release Vol.210 No.-

A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

Park, S R,Kim, H K,Kim, C G,Choi, I J,Lee, J S,Lee, J H,Ryu, K W,Kim, Y-W,Bae, J-M,Kim, N K Cancer Research UK 2008 The British journal of cancer Vol.98 No.8

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m<SUP>−2</SUP> b.i.d.) and docetaxel (25–40 mg m<SUP>−2</SUP>); MTD was 45 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel and RD was 40 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.British Journal of Cancer (2008) 98, 1305–1311. doi:10.1038/sj.bjc.6604312 www.bjcancer.com Published online 25 March 2008

Effect of Antimuscarinic Autoantibodies in Primary Sjögren’s Syndrome

Kim, N.,Shin, Y.,Choi, S.,Namkoong, E.,Kim, M.,Lee, J.,Song, Y.,Park, K. SAGE Publications 2015 Journal of dental research Vol.94 No.5

<P>The presence of functional autoantibodies against the muscarinic type 3 receptor (M3R) has been reported in primary Sjogren's syndrome (pSS). However, the pathogenic role of these autoantibodies in pSS development remains to be elucidated. In this experiment, we investigated a pathologic role of pSS autoantibodies (pSS IgG) associated with downregulation of the major histocompatibility complex I (MHC I) molecule with M3R through internalization. Anti-M3R autoantibodies in purified control and pSS IgG were detected using 4 synthesized cyclic M3R peptides by enzyme-linked immunosorbent assay. The binding reactivity of pSS IgG to M3R in situ was analyzed by a dual immunostaining method. Surface expression, interaction, and internalization of M3R with MHC I were analyzed by immunofluorescence confocal microscopy and biochemical assays. Synthetic cyclic peptides M3RP(205-221) and M3RP(520-527) showed significantly high reactivity with pSS IgG compared to the control IgG or the other 3 peptides (P < 0.05). Significantly high reactivity of pSS IgG to M3R in situ was observed. PSS IgG increased the interaction of membrane M3R with MHC I and induced their internalization in primary human submandibular gland cells. The pSS IgG-induced internalization of M3R with MHC I was significantly inhibited by the cholesterol-sequestering drug filipin. Our novel findingnamely, strong downregulation of the membrane MHC I with M3R through internalization of the cholesterol-rich microdomain associating with anti-M3R autoantibodiescould be an important mechanism contributing to the impaired salivation seen in pSS and linking secretory hypofunction to autoimmune pathogenesis.</P>

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

Kong, T. Y.,Kim, J. H.,Choi, W. G.,Lee, J. Y.,Kim, H. S.,Kim, J. Y.,In, M. K.,Lee, H. S. Springer Science + Business Media 2017 Analytical and bioanalytical chemistry Vol.409 No.6

<P>MAM-2201 is a synthetic cannabinoid that is increasingly found in recreational drug abusers and cases of severe intoxication. Thus, characterization of the metabolic pathways of MAM-2201 is necessary to predict individual pharmacokinetics and toxicity differences, and to avoid toxic drug-drug interactions. Collectively, 19 phase 1 metabolites of MAM-2201 were identified using liquid chromatography-Orbitrap mass spectrometry following human liver microsomal incubations in the presence of NADPH: 7 hydroxy-MAM-2201 (M1-M7), 4 dihydroxy-MAM-2201 (M8-M11), dihydrodiol-MAM-2201 (M12), N-(5-hydroxypentyl)-MAM-2201 (M13), hydroxy-M13 (M14), N-dealkyl-MAM-2201 (M15), 2 hydroxy-M15 (M16, M17), MAM-2201 N-pentanoic acid (M18), and hydroxy-M18 (M19). On the basis of intrinsic clearance values in human liver microsomes, hydroxy-MAM-2201 (M1), N-(5-hydroxypentyl)-MAM-2201 (M13), and hydroxy-M13 (M14) were the major metabolites. Based on an enzyme kinetics study using human cDNA-expressed cytochrome P450 (CYP) enzymes and an immunoinhibition study using selective CYP antibodies in human liver microsomes, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes were responsible for MAM-2201 metabolism. The CYP3A4 enzyme played a prominent role in MAM-2201 metabolism, and CYP1A2, CYP2B6, CYP2C8, and CYP2C9 enzymes played major roles in the formation of some metabolites. MAM-2201 is extensively metabolized by multiple CYP enzymes, indicating that MAM-2201 and its metabolites should be used as markers of MAM-2201 abuse and toxicity.</P>

세관 양광주 방전에서 플라즈마 확산의 완전 해

김동준,정종문,김정현,황하청,정재윤,조윤희,임현교,구제환,최은하,조광섭,Jin, D.J.,Jeong, J.M.,Kim, J.H.,Hwang, H.C.,Chung, J.Y.,Cho, Y.H.,Lim, H.K.,Koo, J.H.,Choi, E.H.,Cho, G.S. 한국진공학회 2010 Applied Science and Convergence Technology Vol.19 No.1

관경이 수 mm인 세관 램프 내부에서 플라즈마의 확산을 조사하기 위하여 이극성(ambipolar) 확산방정식을 해하였다. 반경 방향의 확산에 의한 유리관 벽에서의 플라즈마 소멸 특성시간은 $\tau_r\;=\;(r_0/2.4)^2/D_a$로 주어진다. 반경 $r_0{\sim}1\;mm$이고 이극성 확산계수 $D_a{\sim}0.01\;m^2/s$ 이면, $\tau_r{\sim}17\;{\mu}s$이다. 이는 램프의 교류전원 구동에서 플라즈마를 유지하기 위한 구동 최소 주파수 ~30 kHz에 해당한다. 고전압이 인가되는 전극부에 발생한 고밀도의 플라즈마가 양광주로 확산되는 특성시간은 $\tau_z{\sim}0.1\;s$이다. 고밀도 플라즈마 경계에서의 시간에 대한 확산속도는 $t{\sim}10^{-6}\;s$일 때 $u_D{\sim}10^2\;m/s$이고, $t{\sim}10^{-3}\;s$이면 그 속도는 $u_D{\sim}1\;m/s$로 느려진다. 따라서 램프 길이 ~1 m에 대하여 전극부에서 생성된 고밀도 플라즈마가 양광주 전체로 확산되는 시간은 수 초가 걸린다. The ambipolar diffusion equation has been solved in a fine-tube lamp of a few mm in diameter. In the diffusion of radial direction, the plasma diffuses and vanishes away at the glass wall by recombination with the characteristic time of plasma loss is given by $\tau_r\;=\;(r_0/2.4)^2/D_a$. With the radius $r_0{\sim}1\;mm$ and the ambipolar diffusion coefficient $D_a{\sim}0.01\;m^2/s$, the vanishing time is calculated $\tau_r{\sim}10\;{\mu}s$ which corresponds to the least value of frequency 30 kHz for the sustaining the plasma in the operation of high voltage AC-power. In the diffusion of longitudinal z-direction, a high density plasma generated at the area of a high voltage electrode, diffuses into the positive column with the characteristic time $\tau_z{\sim}0.1\;s$. The plasma diffusion velocity at the boundary of high density plasma is $u_D{\sim}10^2\;m/s$ at the time $t{\sim}10^{-6}$ s and the diffusion velocity becomes slow as $u_D{\sim}1\;m/s$ at $t{\sim}10^{-3}\;s$. Therefore, for the long lamp of 1 m, it takes about several seconds for the high density plasma at the area of electrode to diffuse through the whole positive column space.

단일 및 다중 라이시안 페이딩 채널에서 M-PSK 변조기술에서의 BER 유도

S.M. Shamsul Alam,최광석(GoangSeog Choi) 大韓電子工學會 2012 電子工學會論文誌-TC (Telecommunications) Vol.49 No.4

무선통신에서 페이딩은 피할 수 없는 문제이다. 그러므로 전송신호에 있어서는 BER 형태의 오류개념이 도입된다. 다른 페이딩 채널들 상에서 이러한 오류들의 동작을 인식하는 것이 필요하다. Coherent MPSK의 평균 BER에 대한 수학적인 해법을 얻기 위해서 몇 가지 기법들을 제안한다. 본 논문에서, 느리고 평탄한 라이시안 페이딩 채널 상에 diversity의 영향도 또한 분석되어진다. 여기서, 변조 지표 값 M은 변화하고 이 변화의 효과들 또한 묘사되어진다. 다양한 diversity 값과 페이딩 파라미터에 따른 성능 곡선들은 믿을 수 있는 통신 시스템을 위하여 무선 채널을 설계하고 평가하는데 유용하다. In wireless communication system, fading is an unavoidable problem. Hence, errors in form of BER are introduced with the transmitted signal. It is necessary to recognize the behavior of these errors in different fading channels. To obtain the mathematical solution for the average bit error rate(BER) of coherent MPSK, some techniques are presented. In this paper, the impact of diversity is also analyzed over slow and flat Rician fading channel. In here, the value of modulation index, M is varied and the effects of its variation are also depicted. So, these performance curves with different diversity values and fading parameter are useful to design and evaluate the radio channel for faithful communication system.

Tribology Characteristics in 200 μm of Hexagonal Array Dimple Pattern

Choi, W. S.,Angga, S.H.,Kwon, S. H.,Kwon, S. G.,Park, J. M.,Kim, J. S.,Chung, S. W.,Chae, Y. H. Korean Tribology Society 2015 한국트라이볼로지학회지 (Tribol. Lubr.) Vol.31 No.2

This study investigates the effects of a pattern of 200 μm dimples in a hexagonal array on tribological characteristics. A textured surface might reduce the friction coefficient and wear caused by third-body abrasion and thus improve the tribological performance. There are three friction conditions based on the Stribeck curve: boundary friction, mixed friction, and fluid friction conditions. In this experiment, we investigate the friction characteristics by carrying out the friction tests at sliding speeds ranging from 0.06 to 0.34 m/s and normal load ranging from 10 to 100 N. We create dimple surfaces for texturing by using the photolithography method. There are three kinds of specimens with different dimple densities ranging from 10% to 30%. The dimple density on the surface area is the one of the important factors affecting friction characteristics. Friction coefficient generally decreases with an increase in the velocity and load, indicating that the lubrication regime changes depending on the load and velocity. The fluid friction regime is fully developed, as indicated by the duty number graph. Fluid friction occurs at a velocity of 0.14-0.26 m/s. The best performance is seen at 10% dimple density and 200 μm dimple circle in the hexagonal array.

M-ary SS 시스템을 활용한 고속 전력선 통신 성능에 관한 연구

문경환(K.H. Moon),신명철(M.C. Shin),서희석(H.S. Seo),최상열(S.Y. Choi),최인혁(I.H. Choi),김학만(H.M. Kim),허남영(N.Y. Hur),차재상(J.S. Cha) 대한전기학회 2004 대한전기학회 학술대회 논문집 Vol.2004 No.7