• 한국발생생물학회지:발생과생식
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• 제12권3호
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• pp.297-303
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• 2008

본 논문은 인공적인 단백질인 MCL-1ES BH3M에 관한 것으로 MCL-1ES BH3M를 과발현시 세포사멸을 유도한다. MCL-1L을 주형으로 재조합 PCR을 통해서 MCL-1ES BH3M를 클로닝하였다. 새롭게 클로닝한 단백질인 MCL-1ES BH3M 단백질은 안정성을 유지하기 위해서 PEST 도메인이 제거되어 있으며, 다른 BCL-2 패밀리 단백질과의 결합을 조절하기 위해서 BH3도메인의 Leu-Arg-Arg-Val-Gly-Asp-Gly 서열을 7개의 Ala 잔기로 인위적으로 돌연변이를 유도하였다. MCL-1ES BH3M를 293T 세포에서 과발현할 경우 세포사멸을 유도하였고, 항-세포사멸 단백질인 MCL-1L을 같이 과발현하더라도 세포사멸을 유도하였다. 또한, 과발현시 Caspase 9과 3를 활성화하였으며 면역염색법을 통해서 MCL-1ES BH3M 과발현시 미토콘드리아에 MCL-1ES BH3M 단백질이 부분적으로 위치하는 것을 확인하였다. 이상의 결과로 MCL-1ES BH3M는 Caspase 9과 3의 활성을 통해서 세포사멸을 유도한다. 결론적으로 본 연구는 세포사멸을 유도하는 새로운 molecule을 클로닝하였고, 이 molecule에 의한 세포사멸 기능을 확인하였다.

• Molecules and Cells
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• 제21권1호
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• pp.1-6
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• 2006

Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.

• 한국재료학회지
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• 제3권2호
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• pp.175-184
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• 1993

Nd-Fe-B계에 Co와 Al을 첨가한 자석합금을 진공유도용해로에서 제조하여 이들 합금을 단롤법으로 melt-spun시켜 급냉리본을 얻었다. 제작된 급냉리본의 냉각속도에 따른 자기적 성질의 변화를 조사하였고, 최적의 급냉속도에서 제작된 리본을 파쇄하여 resin bond 자석을 제조하였으며, 이들 급냉리본 및 bond자석의 자기적 성질, 미세구조, 결정구조에 관하여 연구, 조사하였다. 이들 급냉리본의 자기적 성질은 급냉속도에 따라 크게 변하였으며 20m/sec전후에서 최적의 자기적 성질을 보였다. 이때의 급냉리본의 미세조직은 Nd-rich의 입계상이 미세한 N$d_2$F$e_14$B결정립을 둘러싼 cell 형의 구조였으며, 특히 Al이 2.1at%첨가된 리본시료에서는 iHc=15.5KOe, Br=7.8KG, (BH)max=8.5MGOe의 자기적 성질을 나타내었다. 최적의 급냉속도에서 제작된 리본을 polyamide resin과 2.5wt%의 비율로 혼합하여 상온에서 성형, 결합시켜 제작한 bond자석에서 보다 현저히 향상되었으며 유지시간이 8분인 경우 iHc=10.8KOe, Br=7.3KG, (BH)max=8.0MGOe의 값을 가졌다. 한편, 자구구조는 maze pattern이 주로 관찰되어 자화용이축인 C축이 배열되었으며 bond자석에서보다 hot-press 자석에서 자구폭이 보다 작았다.

• E2M - 전기 전자와 첨단 소재
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• 제5권2호
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• pp.216-223
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• 1992

큰 보자력(iHc=19,500 Oe)과 큰에너지적[(BH)$_{max}$=32.50MGOe]을 갖는 Fe-(Ce-Didymium)-B 소결자석의 자구를 Bitter법을 개량한 Colloed SEM 법으로 관찰하였다. C축면의 자구는 소자상태에서 3-4.mu.m의 폭을 갖는 Stripe형이고 C축에 평행한 면은 미로형이다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.113-113
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• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• 약학회지
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• 제45권4호
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• pp.426-430
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• 2001

Cells are eliminated in a variety of physiological settings by apoptosis, a genetically encoded process of cellular suicide. Bak, a member of the Bcl-2 protein family, accelerates apoptosis by an unknown mechanism. We have found a novel cDNA encoding a 101 amino acid protein possessing a Bak-like in our full-length cDNA bank. Bak-like shares the conserved domains BHI and 2 with other proapoptotic proteins but lacks the BH3 domain. Bak-like is expressed in a wide variety of tissues. Like Bak, Bak-like gene product primarily enhances apoptotic cell death following an appropriate stimulus.

• Journal of Gastric Cancer
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• 제3권2호
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• pp.84-87
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• 2003

Purpose: Evidence exists that dysregulation of Bcl-2 family members is involved in the pathogenesis of cancer development. The aim of this study was to explore whether the somatic mutation of proapoptotic Bcl-2 member genes, one of the mechanisms that prolong the survival of cancer cells, is involved in gastric carcinogenesis. Materials and Methods: In the current study, to detect somatic mutations of the DNA sequences encoding the Bcl-2 homology 3 (BH3) domain of the human BAD, BIM, BIK, and Bcl-G genes in 60 advanced gastric adenocarcinomas, we used the polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. Results: The SSCP analysis revealed no mutations in the coding regions of the BH3 domain in the cancers. Conclusion: The data presented here indicate that proapoptotic Bcl-2 member genes, BAD, BIM, BIK, and Bcl-G, may not be mutated in human gastric carcinomas and suggest that these genes might be altered by mechanisms other mechanisms somatic mutation.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 1997년도 추계학술대회 논문집
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• pp.120-123
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• 1997

In this paper, we deal with the effect on magnetic properties when Nd is added to Sr ferrite bonded magnet. First, we choose SrO$_{n}$.Fe$_2$O$_3$(n=5.9), which is nonstoichiomatric composition, as specimen ferrite. Then, we add 5wt% polyvinyl alcohol and calcinate at 12$25^{\circ}C$ under $N_2$ environment for carbon coating on chemical compound specimen. After that we obtain 1.2${\mu}{\textrm}{m}$ single domain powder through grinding process for 18 hours. The single domain Sr ferrite Powder is well mixed with silage coupling and calcium stearate of 1wt% Then, it is kneaded by using polyamide12 as a binder and is pelleted. After adding Nd-Fe-B powder to the pelleted specimen, we injection-mould it under magnetic field by using anisotropic mould. Especially, when we add l3wt% Nd-Fe-B powder to the polyamide12, we obtain excellent magnetic propertiecs which are $_{B}$H$_{C}$=2.65KOe, Br=3.16KG and (BH)$_{max}$=2.61MGOeOeOeOeOe

• E2M - 전기 전자와 첨단 소재
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• 제10권5호
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• pp.440-446
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• 1997

This research has been performed for the fabrication of high quality ferrite plastic magnet. The magnetic properties of S $r_{5.9}$F $e_2$ $O_3$ ferrite bonded magnets by injection moulding with a variety of applied magnetic field were investigated. 0.3wt% CaCO3, 0.2wt% $SiO_2$, 0.5wt% $Al_2$ $O_3$and 0.5wt% N $a_2$ $SiO_3$are added in order to improve the magnetic properties of Sr-ferrite plastic magnets during the powder fabrication. For carbon coating on chemical compound specimen, 5wt% polyvinyl alcohol is added, and then calcinated under $N_2$ environment of 12$25^{\circ}C$. The particle size is distributed from 0.9~1.2${\mu}{\textrm}{m}$ which approximates to the single domain. The obtained Sr ferrite powder is well mixed with silane coupling and calcium stearate of 1wt%. Nest, the specimen is pelleted after kneading each of them with polyamidel2 as a binder. When the temperature of injection and mould were 25$0^{\circ}C$ and 8$0^{\circ}C$ respectively at injection pressure of 200kgf/$\textrm{cm}^2$, the degree of orientation was 85.3% under the applied magnetic field of 12kOe. As the results, when the packing density of Sr ferrite powder was 90wt%, the magnetic properties of Sr ferrite bonded magnet were follows : $_{B}$ $H_{c}$=2.41kOe, Br=3.1kG, (BH)$_{max}$=2.21MgOe. Especially, the Sr-ferrite bonded magnet with 10wt% N $d_2$F $e_{14}$B additive were as follows : $_{B}$ $H_{c}$=2.57kOe, Br=3.14kG and (BH)$_{max}$=2.39MGOe.GOe.GOe.GOe.e.

• E2M - 전기 전자와 첨단 소재
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• 제3권1호
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• pp.36-44
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• 1990

본 연구는 34wt%(5Ce-Didymium)-Fe-1wt%B 합금의 분말입도, 성형압력 및 소결온도 에 따른 자기적 성질에 관하여 연구하였다. 그리고 각각의 자기적 성질에 영향을 주는 인자를 알아내기 위하여 밀도측정, 미세조직 및 자구를 관찰하였다. 미세조직은 금속현미경을 이용하여 관찰하였으며 자구는 Bitter법으로 관찰하였다. 결과는 아래와 같다. (1)분말의 입도와 결정립 크기가 작아질수록 경질자기 특성은 증가하였으며 소결온도가 증가할수록 경질자기 특성도 증가하였다. 그러자 압력은 1000kg/$cm^{2}$일때 가장 좋은 경질자기 특성이 얻어졌다. (2)결정립이 클수록 자구의 구조는 복잡했으며 미세한 결정립일수록 큰 결정립에 비해 큰 보자력을 갖는다. 포화된 후에는 거의 모든 결정립이 단자구였으며 열적으로 탈자되었을 경우에는 모두가 multi-domain였다. (3)가장 우수한 경질자기 특성은 3-5.mu.m의 분말을 사용하여 1080.deg.C에서 소결한 후 590.deg.C에서 열처리한 시편에서 얻어졌으며 (BH)$_{max}$는 214.6kJ.m$_{-3}$이다.