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Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein

  • Chun, Jungmin;Cho, Yeondong;Park, Ki Hoon;Choi, Hanul;Cho, Hansam;Lee, Hee-Jung;Jang, Hyun;Kim, Kyung Hyun;Oh, Yu-Kyoung;Kim, Young Bong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.813-819
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease ($eS770-{\Delta}Fc$) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins ($eS770-{\Delta}Fc$, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non-Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERS-CoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.

A Method of Interoperating Heterogeneous Simulation Middleware for L-V-C Combined Environment (L-V-C 통합 환경 실현을 위한 이기종 시뮬레이션 미들웨어 연동 방안)

  • Cho, Kunryun;No, Giseop;Jung, Sihyun;Keerativoranan, Nopphon;Kim, Chongkwon
    • Journal of KIISE
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    • v.42 no.2
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    • pp.213-219
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    • 2015
  • Simulation is used these days to verify the hypothesis or the new technology. In particular, National Defense Modeling & Simulation (M&S) is used to predict wartime situation and conduct the military training. National Defense M&S can be divided into three parts, live simulation, virtual simulation, and constructive simulation. Live simulation is based on the real environment, which allows more realistic sumulation; however, it has decreased budget efficiency, but reduced depictions of reality. In contrast, virtual and constructive simulations which are based on the virtual environment, have increased budget efficiency, but reduced depictions of reality. Thus, if the three parts of the M&S are combined to make the L-V-C combined environment, the disadvantages of each simulation can be complemented to increases the quality of the simulation. In this paper, a method of interworking heterogeneous simulation middeware for L-V-C combined environment is proposed, and the test results of interworking between Data Distribution Service (DDS) and High Level Architecture (HLA) are shown.

Acoustic Features of Phonatory Offset-Onset in the Connected Speech between a Female Stutterer and Non-Stutterers (연속구어 내 발성 종결-개시의 음향학적 특징 - 말더듬 화자와 비말더듬 화자 비교 -)

  • Han, Ji-Yeon;Lee, Ok-Bun
    • Speech Sciences
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    • v.13 no.2
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    • pp.19-33
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    • 2006
  • The purpose of this paper was to examine acoustical characteristics of phonatory offset-onset mechanism in the connected speech of female adults with stuttering and normal nonfluency. The phonatory offset-onset mechanism refers to the laryngeal articulatory gestures. Those gestures are required to mark word boundaries in phonetic contexts of the connected speech. This mechanism included 7 patterns based on the speech spectrogram. This study showed the acoustic features in the connected speech in the production of female adults with stuttering (n=1) and normal nonfluency (n=3). Speech tokens in V_V, V_H, and V_S contexts were selected for the analysis. Speech samples were recorded by Sound Forge, and the spectrographic analysis was conducted using Praat. Results revealed a stuttering (with a type of block) female exhibited more laryngealization gestures in the V_V context. Laryngealization gesture was more characterized by a complete glottal stop or glottal fry both in V_H and in V_S contexts. The results were discussed from theoretical and clinical perspectives.

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LINEAR MAPPINGS ON LINEAR 2-NORMED SPACES

  • White Jr. Albert;Cho, Yeol-Je
    • Bulletin of the Korean Mathematical Society
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    • v.21 no.1
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    • pp.1-5
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    • 1984
  • The notion of linear 2-normed spaces was introduced by S. Gahler ([8,9,10,11]), and these space have been extensively studied by C. Diminnie, R. Ehret, S. Gahler, K. Iseki, A. White, Jr, and others. For nonzero vectors x,y in X, let V(x,y) denote the subspace of X generated by x and y. A linear 2-normed space (X,v) is said to be strictly convex ([3]) if v(x+y,z)=v(x,z)+v(y+z) and z not.mem.V(x,y) imply that y=ax for some a>0. Some characterizations of strict convexity for linear 2-normed spaces are given in [1,3,4,5,12]. Also, a linear 2-normed space (X,v) is said to be strictly 2-convex ([6]) if v(x,y)=v(x,z)=v(y,z)=1/3v(x+z, y+z)=1 implies that z=x+y. These space have been studied in [2,4,6,13]. It is easy to see that every strictly convex linear 2-normed space is always strictly 2-convex but the converse is not necessarily true. Throughout this paper, let (X,v) denote a linear 2-normed space.

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Rapid Detection of the pathogenic agent of Bacterial white enteritis of Larval and Juvenile Stages in Olive flounder (Paralichthys olivaceus) (넙치(Paralichthys olivaceus)자치어 장관백탁증(Bacterial white enteritis) 원인균의 신속 검출)

  • Mun, Yeong-Geon;Park, Geun-Tae;Son, Hong-Ju;Lee, Sang-Hyeon;Lee, Jeong-Min;Heo, Mun-Su
    • Journal of fish pathology
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    • v.17 no.3
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    • pp.159-169
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    • 2004
  • Bacterial wihte enteritis ocurred by infection of V. ichthyoenteri is a devastating disease in olive flounder (Paralichthys olivaceus) hatcheries in Korea. Since white enteritis has been a problem in aquqtic industries, necessity of a rapid detection method is increased. In an attempt to develop rapid PCR method the detection of V. ichthyoenteri, we examined the 16S-23S rRNA intergenic spacer region(ISR) of V. ichthyoenteri and developed species-specific primer for V. ichthyoenteri. The intergenic spacers were amplified by primers complementary to conserved region of 16S and 23S rRNA genes. The intergenic spacer region between the 16S and 23S rRNA genes of V. ichthoenteri were investigated by PCR fragment length typing and DNA sequencing. Analysis of the ISR sequences showed that V. ichthyoenteri contains one types of polymorphic ISRs. The size of ISRs ranged 348bp length and not contains tRNA genes. Mutiple alignment of representative sequences from different Vibrio species revealed several domains of high sequence variability, and allowed to design species-specific primer for detection of Vibrio ichthyoenteri. PCR. The specific of the primer was examined using genomic DNA prepared from 19 different Vibrio species, isolated 18group Vibrio species. The results showed that the PCR reaction using species-specific primer designed in this study can be used to detect V. ichthyoenteri.

Reconstruction with the 'V-Y-S Flap' for the Facial Defect after the Excision of a Skin Cancer (안면부 피부암 절제 후 발생한 결손 부위에 V-Y-S 피판을 이용한 재건술)

  • Kim, Gyu Bo;Cheon, Ji Seon;Lee, Seung Chan;Cho, An Young;Yang, Jeong Yeol
    • Archives of Plastic Surgery
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    • v.33 no.5
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    • pp.541-545
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    • 2006
  • Purpose: There are many methods for the reconstruction of the facial defect after an excision of a skin cancer; such as skin graft, local flap, free flap, etc... Skin graft has its' limitations; it could remain in different color with in regards of the recipient to donor, with an unfavorable scar. Free flap can lead to big donor site morbidity with long operation time and uncontrolled scar as a disadvantage factor. Compared to the prior, local flap offers several merits; sufficient blood supply, good tissue quality and short operation time. We revised 'V-Y-S flap' for the facial defect, which proved to have favorable outcomes. Methods: Total 7 V-Y-S flaps were performed to patients with skin cancers(six squamous cell carcinoma and one basal cell carcinoma). Two of these flaps were combined with composite grafts, one with full thickness skin graft. Six patients were female and one male. The average diameter of defects after excision was 2.3 cm. The follow-up period was 18 months maximally. Results: We treated seven facial skin cancers with 'V-Y-S flap'. There were no flap necrosis, cancer recurrence and scar contracture as a result. Furthermore, this method also offers a favorable central scar line that is parallel to the nasolabial fold and the nasojugal groove, especially in the nasolabial area and superomedial side of the cheek. With this method, we could cover a maximum diameter of 4cm facial defect. Conclusion: In conclusion, it is suggested that V-Y-S flap is a useful method to cover facial defects after the excision of a skin cancer.

SCORE SEQUENCES IN ORIENTED GRAPHS

  • Pirzada, S.;Naikoo, T.A.;Shah, N.A.
    • Journal of applied mathematics & informatics
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    • v.23 no.1_2
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    • pp.257-268
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    • 2007
  • An oriented graph is a digraph with no symmetric pairs of directed arcs and without loops. The score of a vertex $v_i$ in an oriented graph D is $a_{v_i}\;(or\;simply\;a_i)=n-1+d_{v_i}^+-d_{v_i}^-,\;where\; d_{v_i}^+\;and\;d_{v_i}^-$ are the outdegree and indegree, respectively, of $v_i$ and n is the number of vertices in D. In this paper, we give a new proof of Avery's theorem and obtain some stronger inequalities for scores in oriented graphs. We also characterize strongly transitive oriented graphs.