Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4-O-methyl-ascochlorin in leukemia cells

Shin, J. M.,Jeong, Y. J.,Cho, H. J.,Magae, J.,Bae, Y. S.,Chang, Y. C. Springer Science + Business Media 2016 Apoptosis Vol.21 No.5

<P>4-O-Methyl-ascochlorin (MAC) is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, which was isolated from an incomplete fungus, Ascochyta viciae. Although the effects of MAC on apoptosis have been reported, the underlying mechanisms remain unknown. Here, we show that MAC promoted apoptotic cell death and downregulated c-Myc expression in K562 human leukemia cells. The effect of MAC on apoptosis was similar to that of 10058-F4 (a c-Myc inhibitor) or c-Myc siRNA, suggesting that the downregulation of c-Myc expression plays a role in the apoptotic effect of MAC. Further investigation showed that MAC downregulated c-Myc by inhibiting protein synthesis. MAC promoted the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins, including p70S6 K and 4E-BP-1. Treatment of cells with AICAR (an AMPK activator), rapamycin (an mTOR inhibitor), or mTOR siRNA downregulated c-Myc expression and induced apoptosis to a similar extent to that of MAC. These results suggest that the effect of MAC on apoptosis induction in human leukemia cells is mediated by the suppression of c-Myc protein synthesis via an AMPK/mTOR-dependent mechanism.</P>

Comprehensive study on critical role of surface oxygen vacancies for 2DEG formation and annihilation in LaAlO3/SrTiO3 heterointerfaces

Moon, S. Y.,Moon, C. W.,Chang, H. J.,Kim, T.,Kang, C. Y.,Choi, H. J.,Kim, J. S.,Baek, S. H.,Jang, H. W. Springer Science + Business Media 2016 ELECTRONIC MATERIALS LETTERS Vol.12 No.2

<P>Here we report comprehensive study of 2DEG at a-LAO/STO interfaces in comparison with 2DEG at crystalline LaAlO3 (c-LAO)/STO interfaces. We observe that the oxygen deficient environment during the deposition of LAO overlayer is essentially required to create 2DEG at LAO/STO interface regardless of growth temperature from 25 degrees C to 700 degrees C, indicating that the oxygen-poor condition in the system is more important than the crystallinity of LAO layer. The critical thickness (2.6 nm) of 2DEG formation at a-LAO/STO heterostructure is thicker than (1.6 nm) that at c-LAO/STO. Upon ex-situ annealing at 300 degrees C under 300 mTorr of oxygen pressure, 2DEG at a-LAO/STO interface is annihilated, while that in c-LAO/STO interface is still maintained. With combing these findings and scanning transmission electron microscope (STEM) analysis, we suggest that oxygen vacancies at the LAO surface is attributed to the origin of 2DEG formation at the LAO/STO and the crystallinity of the LAO overlayer plays a critical role in the annihilation of 2DEG at a-LAO/STO interface rather than in the formation of 2DEG. This work provides a framework to understand the importance of prohibiting the LAO surface from being oxidized for achieving thermally stable 2DEG at a-LAO/STO interface.</P>

Distribution of stress state in the Nankai subduction zone, southwest Japan and a comparison with Japan Trench

Lin, W.,Byrne, T.B.,Kinoshita, M.,McNeill, L.C.,Chang, C.,Lewis, J.C.,Yamamoto, Y.,Saffer, D.M.,Casey Moore, J.,Wu, H.Y.,Tsuji, T.,Yamada, Y.,Conin, M.,Saito, S.,Ito, T.,Tobin, H.J.,Kimura, G.,Kanagaw Elsevier Scientific Publishing Co 2016 Tectonophysics Vol.692 No.2

<P>To better understand the distribution of three dimensional stress states in the Nankai subduction zone, southwest Japan, we review various stress-related investigations carried out in the first and second stage expeditions of the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) by the Integrated Ocean Drilling Program (IODP) and compile the stress data. Overall, the maximum principal stress sigma(l) in the shallower levels (<similar to 1 km) is vertical from near the center of forearc basin to near the trench and; the maximum horizontal stress S-Hmax (interpreted to be the intermediate principal stress sigma(2)) is generally parallel to the plate convergence vector. The exception to this generalization occurs along the shelf edge of the Nankai margin where S-Hmax, is along strike rather than parallel to the plate convergence vector. Reorientation of the principal stresses at deeper levels (e.g., >similar to 1 km below seafloor or in underlying accretionary prism) with sigma(1) becoming horizontal is also suggested at all deeper drilling sites. We also make a comparison of the stress state in the hanging wall of the frontal plate-interface between Site C0066 in the Nankai and Site C0019 in the Japan Trench subduction zone drilled after the 2011 Mw 9.0 Tohoku-Oki earthquake. In the Japan Trench, a comparison between stress state before and after the 2011 mega-earthquake shows that the stress changed from compression before the earthquake to extension after the earthquake. As a result of the comparison between the Nankai Trough and Japan Trench, a similar current stress state with trench parallel extension was recognized at both C0006 and C0019 sites. Hypothetically, this may indicate that in Nankai Trough it is still in an early stage of the interseismic cycle of a great earthquake which occurs on the decollement and propagates to the toe (around site C0006). (C) 2015 Elsevier B.V. All rights reserved.</P>

An exploration of the antioxidant effects of garlic saponins in mouse-derived C2C12 myoblasts

Kang, J. S.,Kim, S. O.,Kim, G.-Y.,Hwang, H. J.,Kim, B. W.,Chang, Y.-C.,Kim, W.-J.,Kim, C. M.,Yoo, Y. H.,Choi, Y. H. Spandidos Publications 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.1

<P>In this study, we aimed to confirm the protective effects of garlic saponins against oxidative stress-induced cellular damage and to further elucidate the underlying mechanisms in mouse-derived C2C12 myoblasts. Relative cell viability was determined by 3-(4.5-dimethylthiazol-2-yl)-2.5 diphenyltetrazolium bromide assay. Comet assay was used to measure DNA damage and oxidative stress was determined using 2 ',7 '-dichlorofluorescein diacetate to measure intracellular reactive oxygen species (ROS) generation. Western blot analysis and small interfering RNA (siRNA)-based knockdown were used in order to investigate the possible molecular mechanisms. Our results revealed that garlic saponins prevented hydrogen peroxide (H2O2)-induced growth inhibition and exhibited scavenging activity against intracellular ROS. We also observed that garlic saponins prevented H2O2-induced comet tail formation and decreased the phosphorylation levels of gamma H2AX expression, suggesting that they can prevent H2O2-induced DNA damage. In addition, garlic saponins increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme associated with the induction and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the translocation of Nrf2 from the cytosol into the nucleus. However, the protective effects of garlic saponins on H2O2-induced ROS generation and growth inhibition were significantly reduced by zinc protoporphyrin IX, an HO-1 competitive inhibitor. In addition, the potential of garlic saponins to mediate HO-1 induction and protect against H2O2-mediated growth inhibition was adversely affected by transient transfection with Nrf2-specific siRNA. Garlic saponins activated extracellular signal-regulated kinase (ERK) signaling, whereas a specific ERK inhibitor was able to inhibit HO-1 upregulation, as well as Nrf2 induction and phosphorylation. Taken together, the findings of our study suggest that garlic saponins activate the Nrf2/HO-1 pathway by enabling ERK to contribute to the induction of phase II antioxidant and detoxifying enzymes, including HO-1 in C2C12 cells.</P>

C++ 프로그램의 유지보수 지원 시스템의 설계

김재웅(J. W. Kim),문양선(Y. S. Moon),유철중(C. J. Yoo),김용성(Y. S. Kim),장옥배(O. B. Chang) 한국정보과학회 1994 한국정보과학회 학술발표논문집 Vol.21 No.2B

소프트웨어 개발시 유지보수에 드는 비용이 전체 비용의 40 ~ 80%를 차지하고 있기 때문에 유지보수 단계의 개선없이는 소프트웨어의 생산성을 향상시키기가 어렵다. 따라서 본 논문에서는 유지보수를 지원하는 시스템을 개발 하고자 한다. 이 시스템에서는 1) 정량적으로 측정된 복잡도 값을 제시하여 시험 및 유지보수 계획을 세울 때 자원분배를 적절히 할 수 있도록 도움을 주며, 2) 객체지향 설계 및 프로그래밍 지침을 세워 설계자나 프로그래머 및 유지보수자가 보다 효율적인 시스템 설계를 할 수 있도록 하고, 3) 프로그램에 있는 모듈들을 쉽게 이해할 수 있도록 객체들간의 관계를 시각화하며, 각 객체들에 대해 문서 정보를 제공함으로써 유지보수 노력을 줄이는 데 기여할 수 있도록 하였다.

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.

Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire

Chang, S.,Yang, L.,Moon, Y.M.,Cho, Y.G.,Min, S.Y.,Kim, T.J.,Kim, Y.J.,Patrick, W.,Kim, H.Y.,Mohan, C. Pergamon Press 2009 Molecular immunology Vol.46 No.16

When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited three sequence motifs in their immunoglobulin heavy chains, including increased cationicity in CDR3 (''motif A''), reduced anionicity in CDR2 (''motif B'') and increased aspartate at H50 (''motif C''). The present study was designed to elucidate the extent to which these ANA-associated sequence motifs might be hard-wired into the primary B-cell repertoire in lupus. The immunoglobulin heavy chain sequence of total splenic B-cells, follicular B-cells and marginal zone B-cells from B6.Sle1 congenic mice and C57BL/6 controls were amplified by single-cell PCR and compared. Analysis of the primary immunoglobulin heavy chain repertoire indicated that the first two sequence motifs ''A'' and ''B'' were already encoded in the naive repertoire of B6.Sle1<SUP>z</SUP> mice, whereas the third motif ''C'' was introduced in part by somatic mutation. Site-directed mutagenesis confirmed that non-anionic CDR2 and cationic CDR3 residues in the immunoglobulin heavy chain facilitated nuclear antigen binding in concert, whereas aspartate at H50 strongly vetoed DNA-binding, while preserving nucleosome reactivity. Hence, anti-nuclear antibodies appear to arise as a consequence of two distinct processes-genetically programmed selection of specific CDR charge motifs into the primary immunoglobulin repertoire, with secondary contribution from somatic mutation. Polymorphisms in the lupus susceptibility gene Ly108 that impair central B-cell tolerance may be mechanistically responsible for these early repertoire differences in lupus.

Histiocytosis 症候群의 臨床的 觀察

張永吉,洪鎔宇,李炳勳,崔奏榮,洪彰義 대한소아과학회 1971 小兒科 Vol.14 No.1

C++ 클래스 복잡도의 정량적 평가

김은미(E. M. Kim),유철중(C. J. Yoo),김용성(Y. S. Kim ),장옥배(O. B. Chang) 한국정보과학회 1993 한국정보과학회 학술발표논문집 Vol.20 No.1

소프트웨어 척도는 일반적으로 프로젝트의 계획 및 평가와 같은 소프트웨어 관리 기능면에서 바람직한 특성으로서 객체 지향 접근이라는 새로운 기술에 있어서 특별한 의미를 갖는다. 기존의 접근 방식과는 다른 객체 지향 패러다임을 갖는 소프트웨어의 복잡도 측정을 위한 척도의 필요성이 지금까지 몇몇 연구에서 지적되었다. 본 논문에서는 객체 지향 언어인 Smalltalk와 C++의 부석 결과로부터 얻어진 객체 지향 프로그램의 복잡도에 영향을 주는 용인을 바탕으로, C++ 프로그램 개발시 객체 지향성과 개발의 용이성을 지원하는 클래스들의 구조를 이해하는데 드는 노력도를 측정할 수 있는 척도를 제안 평가 하였다.

인장 및 반복하중하의 균열선단 전위거동과 미세균열 전파의 직접관찰

장영원,박찬향,정호철,이종수 대한금속재료학회(대한금속학회) 1990 대한금속·재료학회지 Vol.28 No.10

An in-situ electron microscope study has been conducted to characterize the fracture and crack tip deformation behavior of metals under tensile and cyclic loading in a transmission electron microscope (TEM). The results show a number of new findings regarding the dislocation behavior near the tip and its relationship to the mode of crack propagation. Dislocation emission at the crack tip was found to depend strongly on the geometry of plastic zone, which contains a dislocation-free-zone(DFZ) just ahead of the crack tip. The difficulty of dislocation emission was, in turn, manifested by the fracture toughness. These experimental results were then compared to the theoretical analysis based on the DFZ model of fracture. Furthermore, this in-situ method has been extended to study the cyclic loading on the behavior of crack-tip-generated dislocations. It is found that dislocations emitted from a crack tip during tensile loading can be retracted and annihilated partially upon unloading. The change of plastic zone, dislocation distribution, and the DFZ during the retraction process were carefully examined using a TV/video camera. Their consequent impact on the crack propagation were then discussed in connection with the previously proposed dislocation theory of fracture and dislocation shielding for a moving crack.