한국인 소아 급성림프모구백혈병에서 mercaptopurine의 독성에 관련된 유전자 다형성 분석

학위논문 (박사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 신희영.Introduction: Despite of marked improvement in survival rates of pediatric acute lymphoblastic leukemia (ALL), drug resistance and recurrence are remaining problems. Genetic polymorphism has been known to be an important factor affecting the efficacy and toxicity of antileukemic agents, thus pharmacogenetic researches have been actively conducted in pediatric ALL. Mercaptopurine (MP) is one of the main chemotherapeutics for ALL, and constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. Throughout previous studies, thiopurine methyltransferase (TPMT) is proved to be one of the most responsible genes in the pharmacogenetics of MP. Recently, mutations of nucleoside diphosphate linked moiety X-type motif 15 (NUDT15) have been shown to be a powerful genetic factor affecting the toxicity and intolerance of MP. In this study, the genetic factors affecting the toxicity of MP were investigated in Korean children with ALL. Patients and Methods: Two-stage pharmacogenetic analyses were performed to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. A total of 185 patients with ALL who were diagnosed and treated at the Seoul National University Children's Hospital were included. First, targeted sequencing was carried out using a novel gene panel of 147 pharmacogenetics related genes and 8 SNPs in 44 patients who received less than 25% of initial dose during maintenance therapy due to MP intolerance. Next, significant genes identified in the first analysis were re-sequenced in a total of 185 patients. The relationship between mutation of each gene identified through sequencing and toxicity or dose of MP were analyzed. Results: As a result of the first stage analysis, the 4 loci which were likely to be most relevant to the toxicity of MP (NUDT15 rs116855232, APEX1 rs2307486, CYP1A1 rs4646422, BAG3 rs78439745) were identified, and 24 variants in 13 genes potentially linked to MP adverse reactions including these 4 loci were selected as final candidates for subsequent validation in a cohort of 185 patients. The distribution of variant alleles were NUDT15 rs116855232 (21.7%), APEX1 rs2307486 (13.5%), ABCC4 rs2274407 (34%), ABCC4 rs3765534 (14.1%), ABCC4 rs11568658 (23.2%), CYP4F2 rs2108622 (51.9%), CYP1A1 rs4646422 (29.1%), SLCO1B1 rs11045879 (55.7%), SLCOB1 rs4149056 (26.5%), ITPA rs1127354 (26%), ITPA rs7270101 (0%), MTHFR rs1801131 (60.5%), MTHFR rs1801133 (28.6%), MTHFR rs1901133 (50.8%), GRIA1 rs4958351 (3.8%), MOCOS rs594445 (48.1%), PACSIN2 rs2413739 (13.5%), BAG3 rs78439745 (7%) and TPMT (* 1 / * 3C, 3.8%). Neutropenia (neutrophil<500/㎕) was observed in 121 patients (65.4%) during the administration of MP. When frequency of neutropenia during MP administration was crosstabulated with variant frequencies, the risk of neutropenia was 4.64 times higher in patients with T allele in ABCC4 rs3765534 (95% CI1.32 to 25.12, P=0.008). Among 121 patients with neutropenia, 15 patients had neutropenia within 30 days (early neutropenia) after starting MP, and the risk of early neutropenia was significantly higher in patients with G allele in APEX1 rs2307486 (OR=3.4495% CI1.04 to 9.89, P=0.02). In addition, the cumulative incidence of early neutropenia was significantly higher in patients with variant forms of APEX1 rs2307486 (AA:AG:GG=66.3%:73%:100%, P<0.001). The cumulative incidence of early neutropenia was also significantly increased in patients with NUDT15 rs116855232 mutations (CC:CT:TT=65.0%:72.2%:100%, P<0.001). Comparing the average doses of MP used in the study, the T allele type of NUDT15 rs116855232 was significantly associated with a lower tolerated dose of MP as 10.5, 19.4 and 28.7 mg/m2/day for TT, CT, and CC genotypes (P<0.001). However, MP doses by TPMT mutations were not significantly different in this study. Conclusion: In conclusion, this study revealed that genetic variation of APEX1 increases the risk of early neutropenia associated with MP, and the variant allele in NUDT15 was related to MP intolerance. In Korean ALL patients, toxicity and tolerance of MP were more affected by APEX1 and NUDT15 than by TPMT, which has a lower variant allele frequency in Asian. Further validation will be needed to confirm the frequency and pharmacogenetic consequences of APEX1 variants in other ethnic groups, including different Asian populationsIntroduction 1 Patients and Methods 4 Patients and treatment 4 Clinical data collection 5 Primary targeted sequencing and analysis 6 Subsequent validation with candidate gene analysis 14 Statistical analysis 20 Ethics statement 21 Results 22 Patients and treatment 22 Results of primary targeted sequencing 24 Results of subsequent candidate gene analysis 27 Neutropenia during maintenance & genotypes 30 Other toxicities during maintenance & genotypes 40 Doses of mercaptopurine, methotrexate & genotypes 43 Survival analysis & genotypes 48 Discussion 50 References 63 국 문 초 록 71Docto

Selective inhibitory effect of epigallocatechin-3-gallate on migration of vascular smooth muscle cells

In order to prevent restenosis after angioplasty or stenting, one of the most popular targets is suppression of the abnormal growth and excess migration of vascular smooth muscle cells (VSMCs) with drugs. However, the drugs also adversely affect vascular endothelial cells (VECs), leading to the induction of late thrombosis. We have investigated the effect of epigallocatechin-3-gallate (EGCG) on the proliferation and migration of VECs and VSMCs. Both cells showed dose-dependent decrease of viability in response to EGCG while they have different IC(50) values of EGCG (VECs, 150 mM and VSMCs, 1050 mM). Incubating both cells with EGCG resulted in significant reduction in cell proliferation irrespective of cell type. The proliferation of VECs were greater affected than that of VSMCs at the same concentrations of EGCG. EGCG exerted differential migration-inhibitory activity in VECs vs. VSMCs. The migration of VECs was not attenuated by 200 mM EGCG, but that of VSMCs was significantly inhibited at the same concentration of EGCG. It is suggested that that EGCG can be effectively used as an efficient drug for vascular diseases or stents due to its selective activity, completely suppressing the proliferation and migration of VSMCs, but not adversely affecting VECs migration in blood vessels.ope

Antimicrobial effect of medical adhesive composed of aldehyded dextran and ε-Poly(L-Lysine).

Infection of surgical wounds is a severe problem. Conventional tissue reattachment methods have limits of incomplete sealing and high susceptibility to infection. Medical adhesives have several advantages over traditional tissue reattachment techniques, but still have drawbacks, such as the probability of infection, low adhesive strength, and high cytotoxicity. Recently, a new medical adhesive (new-adhesive) with high adhesive strength and low cytotoxicity, composed of aldehyded dextran and ε-poly(L-lysine), was developed. The antimicrobial activity of the new-adhesive was assayed using agar media and porcine skin. In the agar diffusion method, inoculated microorganisms that contacted the new-adhesive were inactivated, but this was not dependent on the amount of new-adhesive. Similar to the agar media results, the topical antimicrobial effect of new-adhesive was confirmed using a porcine skin antimicrobial assay, and the effect was not due to physical blocking based on comparison with the group whose wounds were wrapped.ope

Direct-Current Treatment as a Safe Sterilization Method for Electrospun Biodegradable Polymer

Sterilization is an essential process for biodegradable polymers to be used as biomaterials or tissue engineered- scaffolds. The characteristics of biodegradable scaffolds can change due to decomposition of constituent polymers due to high temperature, pressure, or moisture during sterilization. This study investigated direct–current (DC) treatment as a safe method that can prevent structural change and deformation. Treatment of electrospun poly (lactic-co-glycolic acid) (PLGA) with DC showed a bactericidal effect within 40 sec at 4 V. When DC was applied at 6 V to the electrospun PLGA, the bactericidal effect emerged within 30 sec. The morphology of fibers and molecular weight of PLGA polymer was maintained after DC treatment. In contrast, electrospun PLGA exposed to ethylene oxide showed fiber degradation, and gamma or e-beam irradiation resulted in decreased molecular weight. The demonstrated improvement in chemical and physical stability of biodegradable polymers after DC sterilization may help extend their application.ope

Migration of Human Dermal Fibroblast is Affected by the Diameter of the Electrospun PLGA Fiber

Cell migration is an essential activity of the cells in various biological phenomena such as embryonic development, wound healing of damaged tissue, capillary vascularization in angiogenesis and migration of leukocytes to kill the bacteria around the wound site. The properties of nanofibrous surface enhancing cell adhesion, proliferation, migration and differentiation are necessary for application in tissue engineering. Recently, fabricated scaffolds at the nanometer scale are very similar to the architecture of natural human tissue, because of the development of nanofibers. In this study, we observed different cell migration behaviors on PLGA nanofibers with different diameters. 0.4 μm and 1.4 μm PLGA fibers were fabricated by electrospinning. Adhesion of neonatal human dermal fibroblasts (nHDFs) on the PLGA scaffolds was quantified by MTT assay. Real time observation system was used to analyze the migration of nHDF on the 0.4 μm and 1.4 μm PLGA scaffolds. There are no significant differences in cell attachment between 0.4 μm and 1.4 μm PLGA nanofibers. However, the migration was affected by the thickness of the PLGA fiber. The cells were migrated along with the 0.4 μm PLGA fiber but did not cross 1.4 μm PLGA fiber. In this research, it would be evaluated that different diameter of electrospun PLGA fiber effect on the cell migration and proliferation, and it could be applied for the development of the fibrous scaffold in tissue engineering.ope

아토피피부염 환자로부터 유래된 인간화 마우스 모델 구축 및 특성 규명: 아바타 마우스

아토피피부염은 만성적으로 재발하는 염증성 피부질환으로, 최근 30년간 전세계적으로 발생률이 증가하고 있으며 지역, 연령, 성별, 사회문화적 특성에 따라 다양한 유병률을 보이는 heterogeneous한 질병이다. 따라서 환자 개개인에게 적합한 치료 방법을 선택하는 것이 무엇보다 중요하다. 따라서 아토피피부염을 발생 원인에 따라 보다 효과적으로 예방 또는 치료하기 위한 연구가 활발하게 이루어지고 있다. 이러한 연구를 위해 다양한 마우스 모델이 보고되고 있는데 마우스 모델에서의 결과를 아토피피부염 환자에게 적용하는 데에는 한계가 발생한다. 따라서 아토피피부염에 대한 인간화 마우스 모델의 개발은 마우스 모델과 환자간의 차이를 줄이기 위해 필수적이며, 이는 치료 약물 개발을 위해 보다 나은 전임상 도구로 이어질 것이라 생각된다. 따라서 개인 맞춤형 의료의 초석을 AD에 설정할 수 있도록 환자 개개인의 면역 반응 패턴을 구현하는 새로운 맞춤형 마우스 모델 (AVATAR mouse)을 구축하고자 한다. 아바타 마우스는 집먼지진드기에 감작 된 AD 환자에서 유래 한 CD3 + T 세포와 CD3 depleted PBMC를 NOD-scid IL2Rγnull(NSG) 마우스에 이식하여 제작하였다. 아바타 마우스를 4주 동안 집먼지진드기를 감작시켜주고, 4주 후 집먼지진드기를 감작시킨 아바타 마우스에서는 염증 반응이 발생하는 반면 집먼지진드기를 감작시키지 않은 대조군에서는 염증 반응이 발생하지 않는 것을 관찰하였다. 또한 집먼지진드기를 감작시킨 아바타 마우스에서 환자의 CD3 + T 세포가 대조군에 비해 증가하고 4주 후에 집먼지 진드기 항원을 인식한 환자의 CD1c + CD11c +HLADR +FcεRI + 항원 제시 세포가 CD3 + T 세포를 활성화시켜 염증반응을 일으키는 것을 확인함으로써 우리의 아바타 마우스 모델이 항원 특이적 T 세포 반응을 유발한다는 것을 확인하였다. 또한 개개인 아토피피부염 환자와 일치하는 아바타 마우스 간의 임상 지표 상관성을 확인함으로써 아바타 마우스가 실제 환자의 질병 상태를 잘 반영해 줄 것이라 생각된다. 이러한 결과를 통해 아바타 마우스를 통해 환자 개개인별 특이적 면역 반응을 확인하고 실제 새로 개발된 약제에 대한 치료 반응을 미리 확인 및 예측할 수 있기에 가까운 미래에 아토피피부염 환자의 개인맞춤형 치료 가능성을 제시하고자 한다. Atopic dermatitis(AD) is a chronic, relapsing inflammatory skin disease with increasing incidence worldwide. AD shows a variety of immune responses with heterogeneous disease phenotypes. Thus many AD mouse models have been developed, yet the limitation occurs when the findings from mouse model is interpreted into human AD subjects. Therefore, development of humanized mouse model for AD is essential to reduce this gap between mouse model and human subjects, which will lead to more homologous pre-clinical tools for drug development in AD. By establishing the new, customized mouse model (AVATAR mouse) which represents the immune response pattern of individual AD patients, the cornerstone of personalized medicine might be set up in AD. AVATAR mouse was made by using NOD-scid IL2Rγnull (NSG) mouse engrafted with CD3+ T cells and peripheral blood mononuclear cells (PBMCs) derived from AD patients who were sensitized to house dust mite (HDM). The AVATAR mice were treated with HDM ointment for 4 weeks. After 4 weeks, we observed that the inflammatory response occurred in AD AVATAR mice treated with HDM ointment, whereas healthy controls (HC) AVATAR mice with HDM ointment did not. Skin engraftment of human CD3+ T cells increased gradually and maintained its number even after 4 weeks, we also confirmed the presence of human CD1c+CD11c+HLADR+FcεRI+ antigen presenting cells together with human CD3+ T cells, which suggests HDM-specific T-cell responses in our AVATAR mouse. Interestingly, clinical and laboratory correlation between individual AD patients and matched AVATAR mice were also observed. Taken together, our results suggest that AVATAR mouse represents the immune response of individual AD patients, which might enable the individualized, patient-oriented approach to treat AD patients in the near future.open석

생리활성물질의 창상치유 작용과 복합 지지체로써의 적용

Dept. of Medical Science/박사Wound sites in skin must be immediately repaired because the skin isolates and protects from the outside. Wound sites become healing with three processes such as inflammation, proliferation and tissue remodeling. Treatment in wound sites is aiming to accelerate the wound healing, to protect the wound sites and to reduce the pain. A skin substitute, one of the treatment methods in wound sites, is used in complete section that requires epidermis and dermis. A skin substitute used commercially is made of the extracellular matrix (ECM), the living cells, the cytokines and the growth factors. However, these materials have some problems to induct the over expression of matrix metalloproteinase in wound sites and to require the cell culture times and the less validity date. In this study, we investigated the biodegradable scaffolds as a skin substitute. The scaffolds made of poly (lactic-co-glycolic acid) (PLGA) what is one of the most used biodegradable polymers was fabricated using electrospinning. Electrospinning easily fabricates the multi-fiber structure with the polymers. This structure has the advantages to provide the large surface area for cell attachment and the fluid passages. The fabricated scaffolds were investigated to composite with natural bioactive compounds instead of the cytokines and the growth factors what accelerate the wound healing. The natural bioactive compounds instead of them were used (1,3)-(1,6)-β-D-glucans (BGs) and epigallocatechin-3-O-gallate (EGCG). BGs, a natural product of glucose polymers, have immune stimulatory activity that is especially effective in wound healing. EGCG is the major polyphenolic compound in green tea, and has been investigated to regulate the secretion of cytokines and the activation of skin cells during wound healing. First of all, the porous PLGA scaffolds were investigated by electrospinning using different process parameters. The electrospun scaffolds showed the uniformity structures when the scaffolds were fabricated with PLGA (PLA:PGA = 75:25) in HFIP or THF/DMF at 20% (w/v). These process parameters had been used for this study because the scaffolds as a skin substitute were demanded the uniformity shapes. The scaffolds processed with dry ice had a loose connection between the fibers and showed large pore sizes. The infiltration of the adult human fibroblasts was directly improved with the increase of the pore sizes of the scaffolds. Biodegradable scaffolds were sometimes deformed by heat, high temperature, pressure and moisture during sterilization. In this study, the electrospun scaffolds were treated with direct current (DC) for sterilization. During sterilization with DC treatment, the fiber structures were maintained and the microorganism sterilized with a short time. Therefore, DC treatment has the possibility of applying in the sterilization method for biodegradable scaffolds. The scaffolds composed of PLGA and BGs (BGs/PLGA scaffold) or EGCG (EGCG/PLGA scaffold) was investigated using electrospinning. The growth rate of human dermal fibroblasts (HDFs) increased in 50BGs/PLGA scaffolds (PLGA scaffolds included 50 wt% BGs) because BGs improved the HDFs proliferation. HDFs showed the cytotoxicity in PLGA scaffolds included 5 wt% EGCG (5EGCG/PLGA scaffolds) because EGCG induced caspase-3 activity to enhance that caused apoptosis. Therefore, 50BGs/PLGA scaffolds and 1EGCG/PLGA scaffolds (PLGA scaffolds included 1 wt% EGCG) were examined the wound healing effect in the animal study. According to H&E staining results, the re-epithelialization in wound sites and the cell infiltration in scaffolds were significantly accelerated the sites treated with the scaffolds included BGs or EGCG at 2 weeks after scaffold implantation. At 2 weeks, the proliferating cells (Ki-67 staining) in basal layers and the angiogenesis (CD 31 staining) in new dermis were also improved with the scaffolds included BGs or EGCG.In conclusion, BGs/PLGA scaffolds and EGCG/PLGA scaffolds should be applied as a skin substitute for accelerated wound healing. Before application to a skin substitute, the EGCG concentration in a skin substitute should be regulated because the EGCG has cytotoxicity at high concentration.ope

과학교사-연구자간 협력적 워크숍에서 사회적 중재를 통한 구성주의 과학수업에 대한 집합적 이해 과정

학위논문(석사) --서울대학교 대학원 :과학교육과(지구과학전공),2008.2Maste

현황분석을 중심으로

학위논문(석사)--서울대학교 대학원 :법과대학 법학과,2020. 2. 송석윤.위원회란 복수의 자연인으로 구성되어 집단적인 결정을 내리는 합의제 기구이다. 우리나라를 포함한 많은 국가들이 행정수요의 다양화와 행정과정의 민주성 강조로 단임 계층 조직에서 벗어난 위원회 조직을 적극 활용하고 있다. 2019년 현재 「행정기관 소속 위원회의 설치․운영에 관한 법률」에 따른 행정기관위원회는 558개이다. 행정기관위원회는 비효율성과 약한 책임성이란 한계가 있지만, 국가와 시민사회의 경계가 모호해지고 행정부 역할이 커지는 상황 속에서 민간의 참여를 보장하고 정책의 정당성과 전문성을 제고한다는 장점이 있다. 또한 행정부 내 합의제 기구의 설치는 그 자체로 권력을 분산하는 효과도 가져온다. 위원회의 양적 팽창과 함께 위원구성방식에서 공정성․대표성을 확보하기 위하여 국회의 위원추천권을 인정하는 위원회가 늘어나고 있다. 2019년 2월 기준으로 국회의 위원추천권을 인정하는 행정기관위원회는 18개이다. 이 논문은 국회추천권이 인정되는 이들 행정기관위원회의 현황을 파악하고 그 연원과 심사과정을 국회 회의록 및 선행연구들을 통해 조사․분석함으로써 현실에서 기관구성 시 나타나는 권력분립 구현방식을 살펴보고자 하였다. 권력분립원리는 권력(국가기능)을 여러 국가기관에 배분하여 그들 간의 견제와 균형을 통하여 권력을 통제하는 원리이다. 권력남용을 방지하여 국민의 자유와 기본권을 보장할 뿐만 아니라 여러 국가과제를 가장 적합한 기관에 배분함으로써 국가기능을 효율적으로 이행하는 것이 권력분립원리의 헌법적 기능이다. 권력분립원리는 고정불변한 국가조직원리가 아니라 시대적 상황이 변함에 따라 변용하였다. 국민주권주의가 보편화된 현대에는 권력분립이 권력이 아닌 국가기능의 분리를 중심으로 논의되는데, 시민사회 발전 및 행정국가화․정당국가화의 진행으로 전통적인 국가․사회 혹은 입법․행정․사법의 경계가 불분명해지고 권력관계가 다변화되며 권력분립의 주체나 영역이 확장되고 있다. 그렇다고 고전적 권력분립론이 완전히 대체된 것은 아니다. 권력의 속성 상 견제와 균형을 통한 권력억제의 필요성은 오늘날에도 여전히 유효하기 때문이다. 결국 오늘날 권력분립원리는 권력의 균형을 이루는 요소들이 매우 복잡하고 다양해진 상황을 반영하는 동시에 민주주의․법치주의 등의 헌법질서 속에서 권력분립의 본질적 가치를 확보하여야 하는 과제를 안고 있다. 오늘날 권력분립은 권력상호 간의 공화와 협력을 포함하고 있기에 행정부 내 기관인 행정기관위원회에 입법부인 국회가 실질적인 구성권을 행사한다고 하여 대통령의 인사 권한을 침해하고 권력분립의 원칙에 위배된다고 곧바로 단정할 수 없다. 또한 우리나라의 헌법은 미국식의 엄격한 권력분립형이 아니라 의원내각제적 요소를 일부 가미하고 있고, 헌법기관인 헌법재판소 재판관과 중앙선거관리위원회 위원을 입법부․행정부․사법부가 동일비율로 구성하고 있다는 점도 감안할 필요가 있다. 나아가 세계화나 복지국가 등장 등으로 집행부 우위인 행정국가 경향이 두드러지는 오늘날의 현실을 감안할 때, 행정부에 대한 국회의 적절한 인사권 통제를 강화할 필요가 있다는 주장도 행정기관위원회의 국회추천권을 정당화하는 사유 중 하나이다. 하지만 모든 행정기관위원회에 국회가 위원을 추천하게 하는 것 역시 바람직하지 않다. 권력분립의 특성 상 행정기관위원회에 대한 국회추천권을 어디까지 인정할 수 있는지에 대한 표준화된 기준은 성립하기 어렵지만, 구체적인 사안에서 권력분립이 제대로 구현되는지는 권력분립의 본질적 기능과 헌법적 가치들을 비추어 실질적으로 판단할 수 있다. 여러 국가과제들을 어떠한 국가기관들이 어떠한 방식으로 수행할 것인가에 따라 권력분립의 구체적인 형태가 결정되기 때문이다. 그런데 국회추천권이 인정되는 행정기관위원회들의 경우 권력분립원리 자체의 모호함을 감안하더라도 일관적이지 않은 모습을 보였다. 개별적인 논의과정에서 당시 정치 상황에 따라 인정 여부를 판단하였고, 무엇보다 행정부 내 위원회 자체에 대한 체계적인 기준을 마련하고 있지 않기 때문이다. 권력분립원리 상 국민의 기본권 침해 가능성이 상대적으로 높거나 보다 민주적 정당성이 높이 요구되는 경우 행정기관위원회 내 견제장치가 더욱 강하게 요구되는데, 위원회의 법적 위상이나 권한을 나타내는 소속 부처나 실정법상의 행정위원회․자문위원회 구분은 국회추천권 도입 논의에서 크게 고려되지 않았다. 이는 현실과 법 간 괴리가 존재함을 방증한다. 다만, 한 가지 유의미한 점은 지방자치‧인권‧개인정보보호 등 헌법에 규정된 민주주의의 핵심적인 제도 내지 권리를 보호‧보장하기 위한 위원회나 사학분쟁․통상교섭 등 첨예한 이해관계 충돌을 조정하기 위하여 민주적 정당성이 많이 요구되는 위원회는 위원 선임에서 국회의 관여가 허용될 여지가 상대적으로 크게 나타났다는 점이다. 이는 위 위원회들이 전통적인 법집행기능으로 보기 어려운 사무를 담당하거나 헌법적 가치를 보호하기 위해 권력남용을 보다 강하게 규제하여야 하는 경우에 해당하므로, 국민의 대표인 국회의 개입을 보다 넓게 인정하였다고 해석된다. 국회추천권을 부여하는 방식도 구체적으로 살펴보았다. 오늘날 권력분립은 기관 간에만 적용되는 원리가 아니다. 시민사회나 정당의 정치적 역할이 점점 중요해지는 상황에서 권력분립 구현 양상을 제대로 파악하기 위해서는 이들 역시 중요한 고려요소이다. 국회추천권 행사주체와 관련하여 먼저, 헌법기관처럼 입법부․행정부․사법부가 함께 위원을 구성하는 위원회는 총 4개였는데 3개 위원회(개인정보보호위원회, 민주화보상위원회, 주식백지신탁심사위원회)는 법 적용대상이나 위원회 직무 등을 고려한 결과로 보이나 민주화보상위원회의 경우 다른 국무총리 소속 과거사 관련 위원회와 달리 국회추천권을 인정한 특별한 이유를 찾지 못하였다. 나아가 기계적으로 3부에 구성 위원수를 동일 비율로 나누어 추천하는 방식은 우리나라 현실에서 오히려 위원회의 중립성을 해하여 권력분립원리를 제한하므로 가급적 지양하는 것이 바람직할 것이다. 다음, 국회추천권을 국회, 국회의장, 국회 소관 상임위원회 중 어디에 부여하는지를 살펴보았다. 국회에서 다른 처리절차를 거침에 따라 민주적 정당성이나 효율적 임명의 차이가 있을 수 있는데 심사과정에서 이러한 점이 전혀 고려되지 않고 있었다. 또한, 교섭단체의 역할을 구체적으로 명시한 위원회는 지역방송발전위원회와 북한인권증진자문위원회 2개였는데, 정당국가화 현상으로 여당․행정부 대 야당 구조가 권력분립에서 더욱 중요해지고 있음을 감안할 때 교섭단체의 역할을 구체적으로 명시하는 것이 바람직한 측면이 있다. 결론적으로 권력분립의 본질은 권력의 합리화를 통해 국정의 효율을 높이고 궁극적으로 국민의 자유와 권리를 보장하는 것임을 고려하여 국회의 행정기관위원회 위원추천권이 도입․운영될 필요가 있다. 나아가 국회의 추천권을 인정할지 여부뿐만 아니라 임명주체를 누구로 할지 여부나 조문을 얼마나 구체화할지 여부도 위원회 구성의 공정성 및 정당성에 영향을 미치므로 해당 행정기관위원회의 위상과 권한을 고려하여 세심하게 설계할 필요가 있다.A committee is a consensus system that consists of multiple people who make collective decisions. As social issues become more complex and people's demands for democratic governance increase, various types of committees in the government are established to coordinate various conflicts of interests by engaging many experts and citizens in the policy process. In Korea, the government committee system was activated as diverse interests emerged from the rapid changes of Korean civil society since the 1990s. According to Ministry of the Interior and Safety(2019), the number of government committees set up and operated under the current administration is 558 committees under administrative agencies. In order to fulfill its role as a consensus institution that does not remain a transit institution that justifies government policies, the fairness and objectivity of appointing committee members should be secured. This is because the substantial independence of the committee depends on how it is organized. As a result, there has been a move to enhance the fairness and representation of the committee members through the recommendation of the National Assembly, the people's representative. Many cases have been legislated to recognize the right to recommend the National Assembly to the government committee, and a lot of bills have been proposed in the 20th National Assembly. Today, the principle of separation of powers has been transformed into a functional separation of power encompassing republics and cooperation among the parties of power, not a break between the legislative, administrative and judicial branches. Therefore, it cannot be concluded that the legislature violates that principle of separation of powers just by appointing the members of the government committee. Rather, it could have the effect of enhancing the legitimacy of the committee. The Constitutional Court also ruled that the current law which allows the National Assembly, the President, and Chief of Supreme Court to have the right to organize a Private School Dispute Mediation Committee under the Ministry of Education, is fair and constitutional. Moreover, as the administration is gradually strengthening its power due to rising welfare demand, there is growing need for the legislative branch to control the executive branch properly. However, it is questionable whether the National Assembly will recognize the right to recommend committees members without limit. Lawmakers legislative right to form legislation is not limitless. Article 66 Clause 4 of the Constitution stipulates that administrative power belongs to the government headed by the president, and Article 78 specifies the president's right to appoint civil servants. If the National Assembly excessively restricts administrative power beyond the scope of checks and balances, this is not only unconstitutional but could also cause many conflicts in the course of actual operation. Also, because the essence of separation of power is to guarantee the freedom and human rights through rationalization of power, it is not desirable to make National Assembly have the right to appoint members that in turn, will lower the committees expertise and efficiency. After all, it is an important constitutional task to check the president's arbitrary abuse of personnel rights while ensuring the responsibility and efficiency of state affairs without infringing on his right to appoint officials by other state agencies. As for the traditional administrative organization such as the prime minister or the ministries, the scope and method of control of the National Assembly are somewhat institutionalized under related statutes like the Constitution, the National Assembly Act, and the Personnel Management Act. However, the committee-type administrative organization, which has been widely used in modern society due to the diversification of administrative needs and the emphasis on democracy in the administrative process, has not been dealt with sufficiently. The purpose of this paper is to compile and to analyze the current status of the Government Committee's recommendation authority to the National Assembly to find a reasonable distribution of power between the legislature and the administration. The administrative bodies committee with the right to recommend the National Assembly was 18 out of a total of 558. It was difficult to find common features among them because setting the recommendation right depended on the individual political situation at that time without any specific criteria. Whether it is administrative or advisory committees, which are criteria under the Act, was not a significant standard. Also, both the scope of authority and organizational structure of the Committee were not important factor. I just illustrated that it is highly likely that the National Assembly will be allowed to participate in the selection of members of the committees which deals with policy areas of great concern to the people of the time or committees that require a lot of democratic legitimacy. In conclusion, the issue of allowing the government committee to intervene in the National Assembly's personnel affairs was largely decided as a result of political compromise or referring to previous cases without much thought. The government system needs to be designed and operated in such a way as to effectively guarantee the people's freedom and rights through rationalization of power. Therefore, it is necessary to carefully design whether or not the National Assembly will make the right to recommend members of government committee, taking into account the committee's status and authority.제 1 장 서론 1 제 1 절 연구의 배경과 목적 1 제 2 절 연구의 범위와 방법 3 제 2 장 행정기관위원회의 확대와 권력분립론의 전개 7 제 1 절 권력분립의 원리와 기능 7 제 2 절 권력분립론의 역사적 전개 9 Ⅰ. 고전적 권력분립론 9 1. 로크(J. Locke) 9 2. 몽테스키외(Montesquieu) 10 3. 미국 건국의 아버지들(Founding Fathers) 12 4. 고전적 권력분립론의 특징 14 Ⅱ. 20세기 권력분립론의 변용 15 1. 캐기(W. Kägi) 15 2. 뢰벤슈타인(K. Loewenstein) 16 3. 슈테른(K. Stern) 17 4. 기능적 권력분립론의 특징 18 제 3 절 권력분립원리에 관한 헌법해석논쟁 20 Ⅰ. 문제의 소재: 권력분립 개념의 모호성 20 Ⅱ. 미국 연방대법원의 권력분립원리 해석론 20 Ⅲ. 권력분립해석론에 대한 평가 23 제 4 절 행정기관위원회와 권력분립의 현대적 의미 24 Ⅰ. 서설 24 Ⅱ. 새로운 행정조직인 행정기관위원회 25 1. 행정기관위원회의 개념 25 2. 행정기관위원회의 분류 27 3. 행정기관위원회의 필요성 및 한계 29 Ⅲ. 국가권력을 둘러싼 시대적 변화와 행정기관위원회 30 1. 시민사회의 발전 30 2. 행정국가 현상 31 3. 정당의 영향력 확대 32 Ⅳ. 새로운 권력분립의 특징 33 1. 다양한 권력보유주체 등장 33 2. 다층적 영역으로의 확장 35 3. 전통적인 권력분립원리의 존속 36 제 5 절 소결 37 제 3 장 행정기관위원회에 대한 국회추천권 도입 현황 40 제 1 절 행정기관위원회 설치 현황 40 제 2 절 국회추천권이 인정되는 행정기관위원회 현황 42 Ⅰ. 개관 42 Ⅱ. 위원회별 검토 44 1. 의안단계부터 국회추천권이 인정된 경우 44 2. 국회심사과정에 국회추천권이 추가된 경우 59 3. 국회에서 실질적 심사 없이 정치적 타협의 결과로 국회추천권이 신설된 경우 67 제 3 절 국회추천권이 도입 논의 중인 행정기관위원회 현황 74 Ⅰ. 개관 74 Ⅱ. 의안별 검토 75 1. 3부(部)가 위원회 구성권을 행사하려는 의안 75 2. 국회의 추천권을 신설하려는 의안 76 제 4 절 소결 80 제 4 장 국회추천권이 인정되는 행정기관위원회의 분석 82 제 1 절 서설 82 제 2 절 헌법질서와 국회추천권 제도 84 제 3 절 국회추천권이 인정된 위원회의 지위와 권한 87 Ⅰ. 위원회의 법적 지위 및 권한 검토의 필요성 87 Ⅱ. 법적 근거 및 소속기관 88 1. 위원회 설치근거 88 2. 위원회 소속기관 89 Ⅲ. 행정위원회․자문위원회 구분 91 Ⅳ. 위원회 법적 권한 92 Ⅴ. 위원회 업무분야 95 Ⅵ. 민간위원회 여부 97 제 4 절 국회추천권 부여의 방식 98 Ⅰ. 추천권 행사주체 98 1. 3부(部)가 함께 위원을 구성하는지 여부 98 2. 국회 내 추천주체의 차이 99 3. 시민단체 등 다른 기관․단체의 추천권 인정 여부 100 Ⅱ. 교섭단체의 역할 명시 여부 101 Ⅲ. 그 밖의 조문의 구체화 정도 104 1. 국회추천 인원수 104 2. 자격요건 104 3. 사무국 등 지원조직 105 제 5 절 소결 106 제 5 장 정리 및 결론 108 참고문헌 114 Abstract 119Maste

Framework of technology patent monitoring on strategic standpoint and development of technology patent map

학위논문(석사)--서울대학교 대학원 :산업공학과,2005.Maste