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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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    • 제28권6호
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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.

듀록 품종의 Melanocortin-4 Receptor(MC4R) 유전자와 성장형질과의 연관성 분석 (Associations of the Porcine Melanocortin-4 Receptor (MC4R) Gene with Growth Traits in Duroc Pigs)

  • 조규호;김명직;최봉환;전기준;유재원;정현정;김인철;이학교;전광주
    • Journal of Animal Science and Technology
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    • 제49권4호
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    • pp.437-442
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    • 2007
  • 본 연구는 축산과학원에서 보유중인 듀록 품종내에서 MC4R 유전자의 SNP 발현 특성과 육종가에 의한 선발 후 MC4R 유전자 빈도의 변화 및 경제형질에 대한 유전자형간 육종가의 차이를 구명하고자 수행하였다. 1999년부터 2005년까지 검정된 검정성적을 바탕으로 일당증체량, 등지방두께, 90kg 도달일령 및 사료요구율에 대하여 유전력과 유전상관 및 육종가를 추정하였으며, 2003년과 2004년에 출생한 660두에 대한 혈액을 채취하여 MC4R 유전자에 대한 유전자형 및 대립유전자 분석을 실시하였다. 또한 육종가에 의한 선발 후 유전자의 빈도변화를 세대별 그리고 선발군 및 도태군에 대하여 분석하였으며, 육종가의 분석결과를 이용하여 MC4R의 유전자형 효과를 보았다. 분석결과 육종가를 근거하여 선발한 MC4R 유전자형은 세대당 그리고 선발군과 도태군에서 차이를 보였으며, 각 형질별 육종가의 분산분석결과 사료요구율을 제외한 기타 경제형질에서 유의적으로 MC4R 유전자의 효과가 있는 것으로 나타났다. MC4R 유전자의 효과에 대한 보고는 상이한 부분도 있지만 자체 축군에 대한 다형성 분석 및 경제형질과의 연관성 분석에 의하여 축군 및 개량하고자 하는 경제형질에 따라 표지 유전인자로 활용하여 선발반응 및 정확도를 높일 수 있을 것으로 사료된다.

Synthesis of 8-Alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and Evaluation of their Anticonvulsant Properties

  • Sun, Xian-Yu;Jin, Yun-Zhe;Li, Fu-Nan;Li, Gao;Chai, Kyu-Yun;Quan, Zhe-Shan
    • Archives of Pharmacal Research
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    • 제29권12호
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    • pp.1080-1085
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    • 2006
  • A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.

Determination of 4-Methylimidazole and 2-Acetyl-4(5)-tetrahydroxybutylimidazole in Caramel Color and Processed Foods by LC-MS/MS

  • Kim, Tae Rang;Kim, Su Un;Shin, Young;Kim, Ji Young;Lee, Sang Me;Kim, Jung Hun
    • Preventive Nutrition and Food Science
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    • 제18권4호
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    • pp.263-268
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    • 2013
  • In this study, the quick HPLC-MS/MS method for the simultaneous separation of 2-acetyl-4(5)-tetrahydroxybuthylimidazole (THI) and 4-(5)-methylimidazole (4-MI) in alkaline medium was used for caramel color and processed foods in Korea. After a simple sample pretreatment, 51 4-MI-labeled samples were positive for 4-MI and 2 also contained THI. The concentration of 4-MI was 260.5~24, $499.3{\mu}g/kg$ in caramel color, less than $LOD{\sim}1,712.5{\mu}g/kg$ in sauce, 1,242.3, $5,972.2{\mu}g/kg$ in balsamic vinegar, $2,118.3{\sim}5,802.4{\mu}g/kg$ in complex seasoning, $82.7{\sim}5,110.6{\mu}g/kg$ in curry, and $29.9{\sim}464.4{\mu}g/kg$ in soft drinks. The recovery rate of 4-MI was 97.1~111.0% in sauce and 81.9~110.0% in powder and that of THI was 83.6{\sim}106.4% in sauce and 61.2{\sim}99.4% in powder. Our results concluded a safe amount of 4-MI and THI compared to the limit of Korea additive code but the processed foods do not have a limit of caramel color and 4-MI in Korea. Therefore, research and monitoring of 4-MI and THI is needed for processed foods in Korea.

4K UHD급 H.264/AVC 복호화기를 위한 4×4 블록 병렬 보간 움직임보상기 아키텍처 설계 (A Design of 4×4 Block Parallel Interpolation Motion Compensation Architecture for 4K UHD H.264/AVC Decoder)

  • 이경호;공진흥
    • 전자공학회논문지
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    • 제50권5호
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    • pp.102-111
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    • 2013
  • 본 연구에서는 4K UHD($3840{\times}2160$) 영상을 실시간 복호화하기 위한 $4{\times}4$ 블록 병렬 보간 H.264/AVC 움직임보상기를 제안한다. 연산처리 성능을 향상시키기 위해 보간 연산을 $4{\times}4$ 블록 단위로 병렬화시켰으며, 병렬 보간 연산에서 필요한 메모리 대역폭을 확장하기 위해 $9{\times}9$개의 메모리 어레이를 가진 2D 캐쉬 버퍼 구조를 설계하였다. 그리고 2D 캐쉬 버퍼는 검색영역 간 재사용 기법을 적용하여 참조화소의 중복저장을 최소화하였으며, $4{\times}4$ 블록 병렬 보간 필터는 3단(수평 수직 1/2부화소, 대각선 1/2부화소, 1/4부화소) 평면 보간 연산 파이프라인 구조로 설계하여 연산회로를 고속화시켰다. 0.13um 공정에서 시뮬레이션한 결과, 161K게이트의 H.264/AVC 움직임보상기는 동작주파수 150MHz에서 4K UHD급 동영상을 초당 72프레임으로 실시간 처리하는 성능을 보였다.

Synthesis of Higenamine, A Cardiotonic Principle of Aconite Root

  • Chang, Ki-Churl;Choi, Sook-Yun;Lim, Jung-Kyoo;Park, Chan-Woong
    • Archives of Pharmacal Research
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    • 제7권2호
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    • pp.133-136
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    • 1984
  • Higenamine (I), cardiotonic principle of Aconite root, was synthesized from 4-methoxy-phenylacetic acid (II) and .betha.-(3, 4-dimethoxyphenyl)-ethylamine (IV). Condensation of IV with 4-mehoxyphenylacetyl chloride (III) was followed by cyclodehydration yielding 1-(4'-methoxybenzyl)-6, 7- dimethoxy-3, 4-dihydroisoquinoline (VI). Reduction of VI to 1, 2, 3, 4-tetrahydroisoquinoline (VII) and subsequent demethylation provided desired product higenamine, 1-(4'-hydroxybenzyl)-6, 7- dihydroxy-1, 2, 3, 4, -tetrahydroisoquinoline.

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30kW 급 합성가스 열병합 시스템 개발 및 효율 성능평가 (Development and efficiency evaluation of 30kW scale syngas cogeneration system)

  • 박일건;김상태;노귀성
    • 한국응용과학기술학회지
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    • 제36권4호
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    • pp.1427-1433
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    • 2019
  • 본 연구에서는 합성가스의 에너지화를 위한 가스엔진 성능 평가를 수행하였다. 회전수 1800 rpm 조건에서 공기과잉률이 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6 증가에 따른 엔진출력(kWm)과 열효율(%)을 평가한 결과, 공기과잉률 λ 1.4에서 엔진출력 34 kWm를 나타냈으며, 공기과잉률이 증가할수록 엔진 열효율은 전반적으로 감소하는 경향을 보였다. 엔진출력 34 kWm 조건에서 공기과잉률이 1, 1.1, 1.2, 1.3, 1.4 증가시 열효율이 34.2%, 36.9%, 37.2%, 37.4%, 38.1%로 증가하였고, 발전출력을 통한 종합효율은 발전출력 30 kWe 부하조건에서 38.7 kg/h의 연료를 소모하여 32.1%의 발전효율과 냉각수와 배기가스에서의 열회수를 통해 57.3 kW의 폐열을 회수하여 53.8%의 열을 회수하여 총 85.8%의 종합효율을 보이는 것으로 나타났다.

R4SDF/R4SDC Hybrid 구조를 이용한 메모리 효율적인 2k/8k FFT/IFFT 프로세서 설계 (A Design of Memory-efficient 2k/8k FFT/IFFT Processor using R4SDF/R4SDC Hybrid Structure)

  • 신경욱
    • 한국정보통신학회논문지
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    • 제8권2호
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    • pp.430-439
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    • 2004
  • OFDM 방식의 DVB-T 수신기에서 다수 반송파의 변ㆍ복조를 수행하는 8192점/2048점 FFT/IFFT 프로세서 (CFFT8k2k)를 설계하였다. 8192점 FFT와 같이 변환 크기가 큰 경우에는 매우 큰 용량의 메모리가 필요하므로, 메모리 효율적인 설계가 중요하다. 본 논문에서는 R4SDC (Radix-4 Single-path Delay Commutator)와 R4SDF (Radix-4 Single-path Delay Feedback)를 혼합한 Hybrid 구조를 적용함으로써 R4SDC 단일 구조에 비해 약 20%의 메모리를 줄였으며, 2단계 수렴 블록 부동점 스케일링 기법을 적용함으로써 기존의 CBFP 방식에비해 약 24%의 메모리를 감소시켰다. 이와 같은 메모리 효율적인 설계를 통해, 기존 방식의 약 57%의 메모리만으로 구현되었으며, 칩 면적과 전력소모가 크게 감소되었다. CFFT8k2k 코어는 Verilog-HDL로 설계되었으며, 102,000여 개의 게이트, 292k 비트의 RAM, 그리고 39k 비트의 ROM으로 구현되었다. $0.25-{\um}m$ CMOS라이브러리로 합성된 게이트 레벨 netlst와 SDF를 이용한 타이밍 시뮬레이션 결과, 2.5-V 전원전압에서 50-MHz로 안전하게 동작함을 확인하였으며, 8192점 FFT/IFFT 연산에 164-${\mu}\textrm{s}$가 소요되어 DVB-T 사양을 만족하는 것으로 평가되었다. 설계된 CFFT8k2k 코어는 FPGA로 구현하여 정상 동작함을 확인하였으며, 8192점 FFT의 평균 SQNR은 약 60-㏈로 분석되었다.

High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells

  • Hong, Oak-Kee;Yoo, Soon-Jib;Son, Jang-Won;Kim, Mee-Kyoung;Baek, Ki-Hyun;Song, Ki-Ho;Cha, Bong-Yun;Jo, Hanjoong;Kwon, Hyuk-Sang
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권2호
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    • pp.169-175
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    • 2016
  • Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) affect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a pro-inflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of inflammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

체세포복제 소 배반포의 Oct-4 발현과 DNA 메틸화 변화 (Expression and DNA Methylation Change of Oct-4 in Cloned Bovine Blastocysts)

  • 차병현;최정상;황성수;정학재;임기순;양병철;김명직;조재현;성환후;고응규
    • 한국수정란이식학회지
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    • 제23권3호
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    • pp.133-139
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    • 2008
  • DNA methylation is one of the reasons for poor survival of clone animals. The OCT-4 gene is essential for maintaining pluripotency of embryonic stem (ES) cells and early embryos. We previously reported that the 5'-promoter region of Oct-4 gene was a target of DNA methylation and the methylation status was changed variously during embryonic development in bovine. The study conducted to examine the expression and methylation pattern of tissue-dependent differentially methylated region (T-DMR) of Oct-4 gene in bovine somatic cell nuclear transfer (SCNT) and in vitro fertilization (IVF) blastocysts. The Oct-4 gene expression was evaluated by RT-PCR and fluorescence immunocytochemistry. The methylation pattern of T-DMR was analyzed using restriction mapping and bisulfite sequencing methods. The Oct-4 transcripts were highly expressed in IVF, while they were not expressed in SCNT. The Oct-4 protein was not detected or expressed at very low level in SCNT, the intensity of Oct-4 protein, however, was strong in IVF. On the other hand, the T-DMR of Oct-4 gene was hypermethylated in SCNT compared to that of IVF. These results suggested that expression and the failure of demethylation of Oct-4 gene was closely associated with incomplete development of SCNT embryos.