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Performance of Homologous and Heterologous Prime-Boost Immunization Regimens of Recombinant Adenovirus and Modified Vaccinia Virus Ankara Expressing an Ag85B-TB10.4 Fusion Protein against Mycobacterium tuberculosis

  • Kou, Yiming;Wan, Mingming;Shi, Wei;Liu, Jie;Zhao, Zhilei;Xu, Yongqing;Wei, Wei;Sun, Bo;Gao, Feng;Cai, Linjun;Jiang, Chunlai
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.1022-1029
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    • 2018
  • Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. In the present study, we constructed recombinant Ad and MVA expressing an Ag85B-TB10.4 fusion protein (AdH4 and MVAH4) and evaluated the impact of their different immunization regimens on the humoral and cellular immune responses. We found that the viral vector-based vaccines could generate significantly higher levels of antigen-specific antibodies, $IFN-{\gamma}$-producing splenocytes, $CD69^+CD8^+$ T cells, and $IFN-{\gamma}$ secretion when compared with bacillus Calmette-$Gu{\acute{e}}rin$ (BCG) in a mouse model. AdH4-containing immunization regimens (AdH4-AdH4, AdH4-MVAH4, and MVAH4-AdH4) induced significantly stronger antibody responses, much more $IFN-{\gamma}$-producing splenocytes and $CD69^+CD8^+$ T cells, and higher levels of $IFN-{\gamma}$ secretion when compared with the MVAH4-MVAH4 immunization regimen. The number of $IFN-{\gamma}$-producing splenocytes sensitive to $CD8^+$ T-cell restricted peptides of Ag85B (9-1p and 9-2p) and Th1-related cytokines ($IFN-{\gamma}$ and $TNF-{\alpha}$) in the AdH4-MVAH4 heterologous prime-boost regimen immunization group was significantly higher than that in the other viral vector-based vaccine- and BCG-immunized groups, respectively. These results indicate that an immunization regimen involving AdH4 may have a higher capacity to induce humoral and cellular immune responses against TB in mice than that by regimens containing BCG or MVAH4 alone, and the AdH4-MVAH4 prime-boost regimen may generate an ideal protective effect.

The Effects of Bone Morphogenetic Protein-4 and Resorbable Membrane on the Regeneration of Periodontal Tissues (골형태형성단백질과 흡수성차폐막이 치주조직 재생에 미치는 영향)

  • Lim, Sang-Cheol;Kwon, Young-Hyuk;Lee, Man-Sup;Partk, Joon-Bong
    • Journal of Periodontal and Implant Science
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    • v.30 no.4
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    • pp.757-779
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    • 2000
  • The aim of our study is to achieve complete periodontal tissue regeneration by the application of BMP and resorbable membrane. Three beagle dogs aged over one and half years and weighed 14 to 16 kg were used in this study. Mandibular 1st, 2nd premolars were extracted bilaterally. Horizontal furcation defects were induced around 3rd, 4th premolars bilaterally. BMP-4 were applied in the right side with resorbable membranes and only resorbable membranes were applied in the left side respectively. Each animal was sacrificed at 2, 4, and 8weeks, after regenerative surgery. Specimens were prepared with Hematoxylin-Eosin stain and Goldner's modified Masson Trichrome stain for light microscopic evaluation. The results were as follows: 1. At 2 weeks after regenerative surgery, downgrowth of junctional epithelium was observed both in the membraneapplied site and BMP-4-and-membrane-applied site. 2. At 4 weeks after regenerative surgery, resorbable membranes were completely resolved, therefore would not prevent downgrowth of junctional epithelium. New bone formation, new cementum formation and Sharpey's fiber were observed in BMP-4-andmembrane-applied site. 3. At 8 weeks after regenerative surgery, downgrowth of junctional epithelium was observed in the membrane-applied site. But, new cementum formation was observed in the same site. The extensive regeneration of new bone, new cementum and remarkable formation of Shapey's fiber were showed in BMP-4-and-membrane-applied site. 4. Resorbable membranes were resolved via the cell-mediated processes. 5. Periodontal tissue regeneration were better achieved in the BMP-4-andmembrane-applied site than in the membrane-applied site. Within the above results, BMP-4 may have the strong capability to form the new bone and resorbable membrane may be able to prevent the bony ankylosis. However, resolution rate of resorbable membrane may not be enough to protect rapid epithelial downgrowth for ideal periodontal regeneration. In conclusion, I suggest BMP-4 may have the strong possibility to be utilized in the clinical periodontal treat-

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A 2×2 MIMO Spatial Multiplexing 5G Signal Reception in a 500 km/h High-Speed Vehicle using an Augmented Channel Matrix Generated by a Delay and Doppler Profiler

  • Suguru Kuniyoshi;Rie Saotome;Shiho Oshiro;Tomohisa Wada
    • International Journal of Computer Science & Network Security
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    • v.23 no.10
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    • pp.1-10
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    • 2023
  • This paper proposes a method to extend Inter-Carrier Interference (ICI) canceling Orthogonal Frequency Division Multiplexing (OFDM) receivers for 5G mobile systems to spatial multiplexing 2×2 MIMO (Multiple Input Multiple Output) systems to support high-speed ground transportation services by linear motor cars traveling at 500 km/h. In Japan, linear-motor high-speed ground transportation service is scheduled to begin in 2027. To expand the coverage area of base stations, 5G mobile systems in high-speed moving trains will have multiple base station antennas transmitting the same downlink (DL) signal, forming an expanded cell size along the train rails. 5G terminals in a fast-moving train can cause the forward and backward antenna signals to be Doppler-shifted in opposite directions, so the receiver in the train may have trouble estimating the exact channel transfer function (CTF) for demodulation. A receiver in such high-speed train sees the transmission channel which is composed of multiple Doppler-shifted propagation paths. Then, a loss of sub-carrier orthogonality due to Doppler-spread channels causes ICI. The ICI Canceller is realized by the following three steps. First, using the Demodulation Reference Symbol (DMRS) pilot signals, it analyzes three parameters such as attenuation, relative delay, and Doppler-shift of each multi-path component. Secondly, based on the sets of three parameters, Channel Transfer Function (CTF) of sender sub-carrier number n to receiver sub-carrier number l is generated. In case of n≠l, the CTF corresponds to ICI factor. Thirdly, since ICI factor is obtained, by applying ICI reverse operation by Multi-Tap Equalizer, ICI canceling can be realized. ICI canceling performance has been simulated assuming severe channel condition such as 500 km/h, 8 path reverse Doppler Shift for QPSK, 16QAM, 64QAM and 256QAM modulations. In particular, 2×2MIMO QPSK and 16QAM modulation schemes, BER (Bit Error Rate) improvement was observed when the number of taps in the multi-tap equalizer was set to 31 or more taps, at a moving speed of 500 km/h and in an 8-pass reverse doppler shift environment.

Research on soil composition measurement sensor configuration and UI implementation (토양 성분 측정 센서 구성 및 UI 구현에 관한 연구)

  • Ye Eun Park;Jin Hyoung Jeong;Jae Hyun Jo;Young Yoon Chang;Sang Sik Lee
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.17 no.1
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    • pp.76-81
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    • 2024
  • Recently, agricultural methods are changing from experience-based agriculture to data-based agriculture. Changes in agricultural production due to the 4th Industrial Revolution are largely occurring in three areas: smart sensing and monitoring, smart analysis and planning, and smart control. In order to realize open-field smart agriculture, information on the physical and chemical properties of soil is essential. Conventional physicochemical measurements are conducted in a laboratory after collecting samples, which consumes a lot of cost, labor, and time, so they are quickly measured in the field. Measurement technology that can do this is urgently needed. In addition, a soil analysis system that can be carried and moved by the measurer and used in Korea's rice fields, fields, and facility houses is needed. To solve this problem, our goal is to develop and commercialize software that can collect soil samples and analyze the information. In this study, basic soil composition measurement was conducted using soil composition measurement sensors consisting of hardness measurement and electrode sensors. Through future research, we plan to develop a system that applies soil sampling using a CCD camera, ultrasonic sensor, and sampler. Therefore, we implemented a sensor and soil analysis UI that can measure and analyze the soil condition in real time, such as hardness measurement display using a load cell and moisture, PH, and EC measurement display using conductivity.

Transforming growth factor-β promoted vascular endothelial growth factor release by human lung fibroblasts (인간 폐섬유아세포에서 TGF-β 자극에 의한 VEGF 분비)

  • Park, Sang-Uk;Shin, Joo-Hwa;Shim, Jae-Won;Kim, Deok-Soo;Jung, Hye-Lim;Park, Moon-Soo;Shim, Jung-Yeon
    • Clinical and Experimental Pediatrics
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    • v.51 no.8
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    • pp.879-885
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    • 2008
  • Purpose : The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. Methods : Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-${\beta}$ (TGF-${\beta}$), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. Results : 1) The release of VEGF was significantly increased after stimulation with TGF-${\beta}$, and its release was augmented when co-stimulated with PDGF and TGF-${\beta}$. 2) VEGF release induced by PDGF or TGF-${\beta}$ was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-${\beta}$ nor PDGF induced TARC release from lung fibroblasts. Conclusion : Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.

Biological Activity of Ixeris dentata Nakai juice Extracts (씀바귀(Ixeris dentata Nakai) 생즙 추출물의 생리활성)

  • 김명조;김주성;강원희;조미애;함승시;정동명
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.924-930
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    • 2002
  • Ixeris dentata extracts exllibited antimicrobial activity against some bacteria and fungi. Also EtOH extracts showed strong antioxidant activity and RC$_{50}$ value was 28 $\mu\textrm{g}$/mL. The inhibitory effect of Ixeris dentata on the mutagenicity in Salmonella and cytotoxicity on cancer cell were studied. Ixeris dentata extracts showed anti-mutagenic effects of 78.83 and 75.96% on B(a)P in S. typhimurium TA98 and Th100, respectively. These extracts showed 78.72% antimutagenicity on TA100 against MNNG. The Ixeris dentata extract with strong antimutagenic activities was further fractionated by hexane, ethyl acetate, butanol and water. Butanol fraction was found to be highest in antimutagenic activity against MNNG than the other fractions. Butanol fraction of Ixreis dentate revealed the highest cytotoxicity against AS49 human lung carcinoma cells in which cell growth was inhibited by 93.75% at 375 $\mu\textrm{g}$/mL. Hexane fraction of ixeris dentate exhibited 68.56% inhibition against MCF-7 human breast adenocarcinoma cells at 500 $\mu\textrm{g}$/mL. Hexane fraction of Ixeris dentata exhibited 84.91% inhibition against Hep 3B human hepatocellular carcinoma cells at 500 $\mu\textrm{g}$/mL. From these results, it is considered that Ixeris dentata has strong antimutagenic and anticancer effects in vitro. However, these extracts and fractions did not show any cytotoxic effect against 293 cells.

Parkin Interacts with the PDZ Domain of Multi-PDZ Domain Protein MUPP1 (Parkin과 Multi-PDZ Domain Protein (MUPP1) 단백질 간의 PDZ 결합)

  • Jang, Won Hee;Jeong, Young Joo;Choi, Sun Hee;Lee, Won Hee;Kim, Mooseong;Kim, Sang-Jin;Urm, Sang-Hwa;Moon, Il Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.820-826
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    • 2014
  • The localization to specific subcellular sites and the regulation of cell surface receptors and channels are crucial for proper functioning. Postsynaptic density-95/Disks large/Zonula occludens-1 (PDZ)-domain is involved in recognition of and interaction between various proteins, by which the localization and the regulation are mediated. Multi-PDZ domain protein 1 (MUPP1) contains 13 PDZ domains. MUPP1 serves a scaffolding function for structure proteins and signaling proteins, but the mechanism how MUPP1 is stabilized and signalized has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and Parkin. Parkin is an E3 ubiquitin ligase. Loss-of-function mutations of Parkin gene are known to cause an autosomal recessive juvenile parkinsonism. Parkin bound to the $12^{th}$ PDZ domain, but not to other PDZ domains of MUPP1. The C-terminal end of Parkin has a type II PDZ-association motif, which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, Parkin co-localized with MUPP1. When co-expressed with ubiquitin in HEK-293T cells, MUPP1 has been strongly ubiquitinated by Parkin. These findings collectively suggest that MUPP1 is a novel substrate of Parkin and its function or stability could be modulated by Parkin-mediated ubiquitination.

The Changes of Serum Level of Tumor Necrosis Factor-Alpha, Gamma-Interferon and Soluble-Intercellular Adhesion Molecule-1 Relating to the Progression and Treatment of Patients with Pulmonary Tuberculosis (폐결핵의 진행정도 및 치료에 따른 혈청내 Tumor Necrosis Factor-Alpha, Gamma-Interferon 및 Soluble-Intercellular Adhesion Molecule-1의 변화)

  • Kim, Myung-Hoon;Ahn, Joong-Hyun;Moon, Hwa-Sik;Park, Sung-Hak;Song, Jeong-Sup
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1167-1177
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    • 1998
  • Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

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Analysis of Citizen's Attitude to the Foodwaste (I) (음식쓰레기에 관한 실태조사(I))

  • Jang, Won;Kim, Mikyeong;Kang, Changmin;Park, Youngsuk
    • Journal of the Korea Organic Resources Recycling Association
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    • v.5 no.1
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    • pp.43-52
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    • 1997
  • This study was conducted to analysis citizen's attitude and style to the foodwaste from loth Sept. to 30th Sept. in 1996. The research was used questionare method and the analysis was used prequency analysis and cross table method by SPSS (scientific statistics). they answered that the most serious environment problem was waste problem and the best way to settle waste problem was to reduce waste production itself. And they answered that to settle environment problems, it was most important for us to change our life style. But It was not agreed between consciousness and action(execution). Because most of the food-related waste was among household waste, it's settlement was the most importment thing than any other. Nevertheless the seperation of waste was essential to effective incineration, the seperation process was not actually conducted and only a few housewife knew the difference of incinerable and non-incinerable waste. The recycling for the disused dry-cells and garbage is not completly. But we think that if the effective government's recycling counterplan for wastes, foodwaste or wasted dry cell, etc., is estabilished, rates of seperation and collection was increasing. Much usuage of onetime vinyl bag for shopping was become the one of the main cause in increasing the package waste, and so it was needed to use the longlife shopping basket.

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EXPRESSION OF THE GENES OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VON WILLEBRAND FACTOR IN SALIVARY GLAND TUMORS (타액선 종양에서 혈관내피성장인자와 von Willebrand 인자 유전자 발현에 관한 연구)

  • Chung, Ji-Hun;Kim, Ji-Hyuk;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.1
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    • pp.41-51
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    • 2008
  • Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.