Development of additive [¹¹C]CO₂ target system in the KOTRON-13 cyclotron and its application for [¹¹C]radiopharmaceutical production

Moon, B.S.,Lee, H.J.,Lee, W.K.,Hur, M.G.,Yang, S.D.,Lee, B.C.,Kim, S.E. North-Holland Physics Pub 2015 Nuclear instruments & methods in physics research. Vol.356 No.-

The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [<SUP>11</SUP>C]CO<SUB>2</SUB>, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [<SUP>11</SUP>C]CO<SUB>2</SUB> production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [<SUP>11</SUP>C]CO<SUB>2</SUB> production for 30min irradiation at 60μA (86.6+/-1.7GBq in the target at EOB) was observed at a thickness of 19μm with HAVAR® material as a target foil and a target loading pressure of 24bar with nitrogen plus 300ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [<SUP>11</SUP>C]CO<SUB>2</SUB> production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [<SUP>11</SUP>C]PIB, [<SUP>11</SUP>C]DASB, [<SUP>11</SUP>C]PBR28, [<SUP>11</SUP>C]Methionine and [<SUP>11</SUP>C]Clozapine, the radiochemical yields were shown to be 25-38% (decay corrected) with over 166GBq/μmol of specific activity. Consequently, the additive carbon-11 target system was successfully developed in only one output port of the KOTRON-13 cyclotron and exhibited the stable production of C-11 labeled radiopharmaceuticals.

Aggravation of post-ischemic liver injury by overexpression of A20, an NF-κB suppressor

Yu, J.,Lee, H.S.,Lee, S.M.,Yu, H.C.,Moon, W.S.,Chung, M.J.,Park, J.W.,Park, B.H. Elsevier Science Publishers 2011 Journal of hepatology Vol.55 No.2

Backgroud & Aims: A20 is an intracellular ubiquitin-editing enzyme that plays an important role in the negative feedback regulation of NF-κB activation in response to a diverse range of stimuli. Liver ischemia/reperfusion injury is associated with rapid activation of NF-κB signaling, but the role of NF-κB in hepatic ischemia/reperfusion injury remains controversial. The NF-κB signaling pathway mediates both protective and deleterious effects in the liver. Here, we examined whether A20 inhibited or aggravated hepatic ischemia/reperfusion injury. Methods: We used IκBα super-repressor as a positive control and overexpressed A20 and IκBα super-repressor in the liver of C57BL/6 mice. Mice underwent 45min of partial hepatic ischemia and were then reperfused. Results: Protein level of A20 was increased after reperfusion. Mice subjected to ischemia/reperfusion injury showed increased NF-κB activation, as evidenced by phosphorylation of IκBα and nuclear translocation of NF-κB. Prior transfection with Ad-A20 or Ad-IκBα super-repressor attenuated NF-κB activation and aggravated liver injury. Serum aminotransferases and proinflammatory cytokines, hepatocellular necrosis, and hepatic neutrophil infiltration were markedly increased compared to those of uninfected or control virus infected mice. In addition, A20 abolished the beneficial effect of ischemic preconditioning. Conclusions: Our results suggest that inhibition of NF-κB activation by A20 aggravated partial hepatic ischemia/reperfusion injury. Understanding how the NF-κB pathway plays a role in directing a clinical outcome may lead to better prospects of more rational approaches to reduce post-ischemic liver injury.

Inhibition of Porcine Endogenous Retrovirus by Multi-Targeting Micro RNA Against Long Terminal Region

Chung, H.-C.,Nguyen, V.-G.,Oh, W.-T.,Huynh, T.-M.-L.,Moon, H.-J.,Lee, J.-H.,Kim, H.-K.,Park, S.-J.,Park, B.-K. Elsevier 2017 Transplantation proceedings Vol.49 No.9

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect.</P> <P><B>Methods</B></P> <P>miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer. The inhibition efficiency between miRNAs was compared based on their inhibition of different PERV genes: long terminal repeats (LTR), gag, and pol. Both relative quantitative real-time polymerase chain reaction (PCR) and C-type reverse transcriptase activity were performed.</P> <P><B>Results</B></P> <P>The results demonstrated that miRNA targeting the LTR region degraded the target sequence, and simultaneously inhibited the mRNA expression of both gag and pol genes of PERV. The LTR1, LTR2, and dual LTR1 + LTR2 miRNA inhibited 76.2%, 22%, and 76.8% of gag gene expression, respectively. Similarly, the miRNA was found to knock down the pol gene expression of 69.8%, 25.5%, and 77.7% for single targeting miRNA (LTR1 and LTR2) and multi-targeting miRNA (LTR1 + LTR2), respectively. A stable PK15 clone constitutively expressed dual LTR1 + LTR2 miRNA and exhibited higher inhibitory up to 82.8% and 92.7% of the expressions of the gag and pol genes, respectively. Also, the result of co-cultivation of dual LTR1 + LTR2 miRNA transfected PK15 cell with a human cell line inhibited expression of LTR, gag, and pol genes of PERV.</P> <P><B>Conclusions</B></P> <P>In conclusion, this study suggested that the LTR might be an alternative target for gene silencing of PERV, and that multi-targeting miRNA had better inhibitory effect than single- targeting miRNA. In an in vitro model, the presence of miRNA was able to reduce PERV infectivity in a human cell line.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This study suggested that the LTR might be an alternative target for gene silencing of PERV, and that multi-targeting miRNA had better inhibitory effect than single- targeting miRNA. </LI> <LI> In an in vitro model, the presence of miRNA was able to reduce PERV infectivity in a human cell line. </LI> </UL> </P>

심혈관질환의 위험인자로서의 endothelial nitric oxide synthase의 SNP 연구

윤수인,문제성,신철,박현영,이정복,조인호 국립보건연구원 2000 국립보건원보 Vol.37 No.-

Generation of anti‐tumour immune response using dendritic cells pulsed with carbonic anhydrase IX‐<i>Acinetobacter baumannii</i> outer membrane protein A fusion proteins against renal cell carcinoma

Kim, B.‐,R.,Yang, E.‐,K.,Kim, D.‐,Y.,Kim, S.‐,H.,Moon, D.‐,C.,Lee, J.‐,H.,Kim, H.‐,J.,Lee, J.‐,C. Blackwell Publishing Ltd 2012 Clinical and experimental immunology Vol.167 No.1

<P><B>Summary</B></P><P>Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma (RCC), serves as a potential target for RCC‐specific immunotherapy using dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient for generation of a therapeutic anti‐tumour immune response against RCC. In this study, in order to generate a potent anti‐tumour immune response against RCC, we produced recombinant CA9‐<I>Acinetobacter baumannii</I> outer membrane protein A (AbOmpA) fusion proteins, designated CA9‐AbOmpA, and investigated the ability of DCs pulsed with CA9‐AbOmpA fusion proteins in a murine renal cell carcinoma (RENCA) model. A recombinant CA9‐AbOmpA fusion protein was composed of a unique proteoglycan‐related region of CA9 (1–120 amino acids) fused at the C‐terminus with transmembrane domain of AbOmpA (1–200 amino acids). This fusion protein was capable of inducing DC maturation and interleukin (IL)‐12 production in DCs. Interaction of DCs pulsed with CA9‐AbOmpA fusion proteins with naive T cells stimulated secretion of IL‐2, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α in T cells. Lymphocytes harvested from mice immunized with DCs pulsed with CA9‐AbOmpA fusion proteins secreted IFN‐γ and showed a specific cytotoxic activity against CA9‐expressing RENCA (RENCA‐CA9) cells. Administration of CA9‐AbOmpA‐pulsed DC vaccine suppressed growth of RENCA‐CA9 cells in mice with an established tumour burden. These results suggest that DCs pulsed with CA9‐AbOmpA fusion proteins generate a specific anti‐tumour immune response against RCC, which can be utilized in immunotherapy of RCC.</P>

C++ 프로그램 구성성분들간의 관계표현 기법에 관한 연구

전형수(H. S. Jeon),문양선(Y. S. Moon),유철중(C. J. Yoo),장옥배(O. B. Chang) 한국정보과학회 1997 한국정보과학회 학술발표논문집 Vol.24 No.1A

유지보수 활동은 변경된 모듈들과 직접적으로나 간접적으로 상호작용하는 모듈들에 대해 행해져야 한다. 유지보수 활동은 유지보수자가 프로그래머가 아닐 경우가 많고, 프로그램 이해가 선행되어야 함으로 많은 어려움이 따른다. 따라서, 프로그램의 분석, 이해, 수정, 재공학, 테스팅, 디버깅등 유지보수 및 관련 활동들에 도움을 줄 수 있는 도구나 효과적인 프로그램 표현법을 포함하는 유지보수 환경이 요구된다. 본 논문은 C++ 프로그램을 기반으로 그러한 유지보수 활동들에 도움을 줄 수 있는 프로그램 구성성분들간의 관계 표현 기법에 관해 연구하였다. 이 표현기법은 클래스간, 메소드간에 발생하는 자료의존성 및 제어의존성 관계를 중심으로 원시프로그램을 분석함으로써, 클래스간의 관계, 메소드간의 관계를 표현해주고, 또한 클래스별 메소드 재사용 정보를 제공하여 메소드간의 의존도를 보여줌으로써 테스팅이나 디버깅 활동에도 도움을 줄 수 있다.

High-Spin Structure of 117Te

C.-B. Moon 호서대학교 기초과학연구소 1998 기초과학연구 논문집 Vol.6 No.1

High-spin states of the 115Te were studied by in-beam spectroscopy with the 103Rh(I8O, p3n) fusion-evaporation reaction at a beam energy of 85 MeV . y-y coincidence and y-y angular correlation analyses were employed for determining the level scheme of ll7Te. The previously known states based on the vh11/2 orbital have been widely extended and some states have been corrected. Based on the TRS calculations, many unusually low-lying states in their excitation energies have been assigned to noncollective oblate states built on various quasiparticle configurations with B2 ~ 0 .1 7 and y = 60°.

Phase 1 and Pharmacokinetic Drug-Drug Interaction Study of Metformin, Losartan, and Linagliptin Coadministered With DW1029M in Healthy Volunteers

Moon, S. J.,Kim, S. Y.,Lim, C. H.,Jang, H. B.,Kim, M. G.,Jeon, J. Y. Sage 2017 Clinical pharmacology in drug development Vol.6 No.4

<P>We investigated botanical drug-pharmaceutical drug interactions between DW1029M (a botanical extract of Morus alba linne root bark and Puerariae radix) and metformin, losartan, and linagliptin in the steady state. Three studies were conducted as randomized, open-label, 2-period, 2-treatment, multiple-dose, 2-way crossover designs. Eligible subjects received metformin (500 mg twice daily), losartan (50 mg once daily), or linagliptin (5 mg once daily) with DW1029M (300 mg x 2T twice daily) every 12 hours on days 1 through 6 and a single dose on the morning of day 7. Coadministration of DW1029M with metformin, losartan, or linagliptin had no clinically relevant effects based on the area under the plasma concentration-time curve (AUC t) geometric least-squares mean ratio (GMR) -AUC t GMR, 89.7; 90% confidence interval (CI), 81.0-99.4 for metformin; AUC t GMR, 96.2; 90% CI, 86.3-107.1 for losartan; and AUC t GMR, 89.7; 90% CI, 83.2-96.6 for linagliptin. In addition, coadministration of DW1029M did not have any clinically meaningful effect on the maximum plasma concentration (C-max, (ss)) -C-max, (ss) GMR, 87.3; 90% CI, 76.2-100.0 for metformin; C-max,C- ss GMR, 90.5; 90% CI, 78.3-104.6 for losartan; and C-max,C- ss GMR, 81.4; 90% CI, 69.5-95.3 for linagliptin. Coadministration of DW1029M with metformin, losartan, or linagliptin was well tolerated.</P>

Tailoring metal-oxide interfaces of oxide-encapsulated Pt/silica hybrid nanocatalysts with enhanced thermal stability

Moon, S.Y.,Naik, B.,Jung, C.H.,Qadir, K.,Park, J.Y. Elsevier Science Publishers 2016 CATALYSIS TODAY - Vol.265 No.-

<P>We report the fabrication of metal-oxide (m-oxide) hybrid nanocatalysts with oxide encapsulation (Pt/SiO2@m-oxide; m-oxide =TiO2, Nb2O5, Ta2O5, CeO2) using a simple surface-modification chemical process. The synthesized m-oxide hybrid nanocatalysts with oxide encapsulation have two advantages: tailoring the metal-support interaction and achieving higher thermal and chemical stability. Briefly, Pt nanoparticles (NPs) capped with polyvinylpyrrolidone were successfully assembled on functionalized SiO2 via electrostatic interactions, and then an ultrathin layer of m-oxide was coated on the surface. Transmission electron microscopy studies confirmed that the Pt NPs were uniformly dispersed and distributed throughout the surface of the SiO2 with a thin layer of m-oxide. In particular, energy-dispersive X-ray spectroscopy line mapping was employed to ensure the presence of a uniformly coated thin oxide layer of constituent elements. The metal NPs were found well exposed to the outer surface, enabling surface characterization, including chemisorption and X-ray photoelectron spectroscopy. Even after calcination at 600 degrees C, the structure and morphology of the hybrid nanocatalysts remained intact, confirming high thermal stability. We investigated the effect of different types of m-oxide coating, an active support material, on the performance of catalytic activity for CO oxidation for the Pt/SiO2@m-oxide hybrid nanocatalysts with well-exposed Pt nanoparticles. We carried out CO oxidation over the hybrid nanocatalysts and found that metal-oxide interfaces play important roles that influence catalytic activity. Designing such metal-oxide hybrid structures with thin oxide encapsulation represents a critical step in the advancement of model catalytic systems for investigating the metal-support interaction with improved thermal stability. (C) 2015 Elsevier B.V. All rights reserved.</P>

C++ 프로그램의 구조도 생성을 위한 역공학 도구의 설계 및 구현

조혜경(H. G. Cho),문양선(Y. S. Moon),신현철(H. C. Sin),김용성(Y. S. Kim),장옥배(O. B. Chang) 한국정보과학회 1995 한국정보과학회 학술발표논문집 Vol.22 No.2B

소프트웨어 개발 기법 중 객체지향 기법은 二 특성으로 인해 소프트웨어 생산성 증진에 많은 도움을 주고 있다. 그러나, 객체지향 기법의 특성 중 상속성 및 다형성은 복잡한 메시지 전달의 원인이 되어 프로그램 이해에 어려움을 준다. 이런 단점을 극복하기 위해 C++ 언어로 작성된 프로그램을 동적 분석을 통해 메시지 전송 객체와 메시지 수신 객체간의 구조를 계층적으로 가시화 시켜주는 구조도 생성 도구의 개발이 필요하다. 본 연구에서는 이러한 구조도 생성 도구를 설계하고 구현한다.