차세대 박막 트랜지스터를 위한 효율적인 용액공정기반 반도성 단일벽 탄소나노튜브의 박막 형성 방법들에 관한 연구

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 전기·정보공학부, 2020. 8. 홍용택.As the demand for flexible and stretchable electronic devices increases, underpinning technologies of system implementation based on the solution-process have been tremendously developed. In particular, solution-processed random networks of semiconducting single-walled carbon nanotubes (SWCNTs) have been widely studied as suitable semiconducting materials for thin-film transistors (TFTs) in next-generation novel applications such as large-area active matrix for lighting emitting devices or biosensors due to their superior electrical and mechanical properties. Furthermore, low-cost and low-temperature processability of highly purified semiconducting SWCNTs with dispersed ink facilitates realizing large-area flexible and stretchable electronic systems. Among various deposition methods of SWCNT based on the solution-process, the easiest and the most effective method to fabricate the SWCNT TFT is directly dipping the substrate into the SWCNT ink, resulting in highly-feasible and highly-uniform deposition of SWCNT onto the large-area substrate, which is called direct dipping method. However, there are limitations to utilize it for the mass-production and commercialization at the related industry. First, this method exhibits low fabrication throughput due to a very long deposition time of SWCNT. And moreover, additional patterning process is needed because the substrate is wholly immersed into the SWCNT solution during dipping process. Therefore, to overcome these issues, some engineering modifications of strategy should be developed. In this Ph. D. dissertation, I developed two facile and effective fundamental technologies, which are multi-dipping technique and self-patterning technique (inkjet-printing of PLL technique), to resolve the aforementioned issues of direct dipping method. Multi-dipping technique is repeatedly both soaking a substrate into SWCNT solution with a very short time and rinsing the substrate each time for dramatically significant reduction of total deposition time of SWCNTs networks instead of soaking the substrate into the solution with a very long time. Compared to the conventional dipping method, this technique reduced the overall process time by more than half and improved the electrical characteristics of SWCNT TFTs at the same time. In addition, in order to achieve simultaneous patterning of the SWCNT layer during the direct dipping process, I inkjet-printed the surface functionalization material, especially the poly-L-lysine (PLL) material, enhancing the attachment of the semiconducting SWCNT at the region where we want to attach the SWCNTs. Only on top of PLL-patterned region, the networks of semiconducting SWCNTs were formed during dipping process although the substrate was wholly immersed into the SWCNT solution. Then, I combined the newly-desired two techniques for effectively fabricating the SWCNT TFT based on the direct dipping method and investigated the feasibility and applicability of the combined technology for the implementation of high-throughput and high-resolution SWCNT TFTs. I defined it as fast and self-patterning technique. In this dissertation, verification was conducted based on two criteria which are large-area scalability and micro-patternability, and for the verification of the latter one, I utilized electrohydrodynamic (EHD)-based printing technology that enables effective fabrication of fine pattern. The two primary purposes of this dissertation are to develop the technologies for effective deposition of in-situ patterned high-quality SWCNT film at the desired area onto the large-area substrate and to investigate the feasibility of the integrated technique for the implementation of future electronic applications. Furthermore, low-temperature processability and excellent mechanical flexibility of SWCNT networks could provide a guideline for implementing roll-to-roll (R2R) fabrication of high-throughput, high-resolution, and high-performance SWCNT TFT array, which is ultimately for the commercialization of future advanced flexible/stretchable electronic applications.최근 유연 및 신축성 전자 소자 응용에 대한 수요가 증가함에 따라, 용액공정기반의 시스템을 구현하는 기반 기술들이 계속해서 발전해오고 있다. 특히, 용액공정기반으로 제작된 반도성 단일벽 탄소나노튜브의 랜덤한 네트워크는 전기적, 기계적으로 우수한 성질을 가지고 있어, 대면적 액티브 매트릭스 기반의 발광 소자 및 센서와 같은 다양하고 새로운 차세대 응용 소자의 기본이 되는 박막 트랜지스터 (TFT)의 반도체층 물질로서 널리 연구되어 왔다. 또한, 저비용, 저온 공정이 가능한 분산된 형태의 고순도 반도성 단일벽 탄소나노튜브용액은 대면적의 유연/신축성 전자 소자로의 응용을 가능하게 해주었다. 이 때, 용액 공정 기반으로 탄소나노튜브 네트워크를 형성할 수 있는 여러 방법들 중에서, 박막 트랜지스터 소자의 채널 영역을 쉽고 효율적으로 제작하기 위한 방법 중 하나는, 직접 기판을 단일벽 탄소나노튜브 용액에 담그는 직접 담그는 방법(Direct dipping method)의 형태이며, 이는 대면적에 단일벽 탄소나노튜브를 매우 쉽고 균일하게 형성할 수 있다. 하지만 이 방법에는 크게 두 가지의 기술적인 한계점들이 존재한다. 우선, 수용액 형태의 용액을 사용하게 되면 매우 긴 공정 시간으로 인해 그 수율이 매우 낮아지게 되며, 다른 하나는 기판 전체가 용액으로 들어가기 때문에 이로부터 추가적인 패터닝 과정이 필요로 한다는 점이다. 따라서, 이 문제점들을 해결하기 위하여, 본인은 다양한 공학적인 접근 방법들을 시도해 보았다. 본 학위 논문에서는, 위에서 언급된 직접 담그는 방법의 문제점들을 해결하기 위한 새로운 쉽고 효과적인 기반 기술들을 개발하였다. 첫 번째 기술 (multi-dipping technique, 반복적 담금기법)은 기판을 용액에 오랜 시간 담가 두는 이전의 방법과는 달리, 기판을 탄소나노튜브 용액 안에 짧은 시간 동안만 담그고 이를 탈 이온수를 이용하여 세정한 뒤, 앞에서 언급한 공정을 계속해서 반복하여 준다. 이는 기존의 직접 담그는 방법과는 달리 단일벽 탄소나노튜브 기반의 박막 트랜지스터의 공정 시간을 절반 이상 감소시켜줄 뿐 아니라, 그 전기적인 특성 또한 향상시켜준다. 또한, 두 번째 기술 (self-patterning technology, 표면처리물질 인쇄공정기법)은, 반도성 단일벽 탄소나노튜브와 기판 사이의 접착력을 좋게 해주는 표면처리물질을 채널을 형성하고자 하는 부분에만 잉크젯프린팅을 해주어 원하는 패턴을 형성한다. 특히 본 논문에서는 표면처리물질로서 poly-L-lysine (PLL)을 이용하였다. 이 기술을 이용할 경우, 기판 전체를 탄소나노튜브 용액에 담금에도 불구하고 반도성 단일벽 탄소나노튜브 네트워크는 오로지 추가적인 패터닝과정 없이도 공정 과정 내에서 스스로 표면처리물질 (PLL)이 인쇄된 부분에만 형성됨을 확인할 수 있었다. 또한, 단일벽 탄소나노튜브 기반의 박막 트랜지스터를 보다 효율적으로 형성해주기 위하여 두 기술을 결합하여 새로운 하나의 기술로 정의 (fast and self-patterning technique)한 후, 해당 기술이 높은 수율 및 해상도를 가지는 단일벽 탄소나노튜브 기반 박막 트랜지스터를 형성할 수 있을지에 대한 실현 및 적용 가능성을 검증하였다. 검증과정에서는, 대면적 소자 제작에 적용 가능할 수 있는지에 대한 부분과 미세화된 소자 제작에 적용 가능한지에 대한 부분, 총 두 가지 기준점을 가지고 연구를 진행하였으며, 이 중에서 미세 패턴 가능성을 보기 위해서는 미세 패턴을 효율적으로 형성할 수 있는 전기수력학방식의 프린팅 기법 (EHD printing)을 활용하였다. 본 학위논문은 다양한 기판에서 원하는 위치에 효과적으로 고품질의 단일벽 탄소나노튜브를 붙여줄 수 있는 기술들을 개발하고, 그 기술들을 결합하여 미래의 전자 소자 제작에 적합한지에 대한 적용가능성을 평가해 보는 것을 주 목적으로 하였다. 또한, 단일벽 탄소나노튜브 물질의 저온 공정 가능성과 물질 자체가 가지고 있는 우수한 기계적 특성은 본인이 개발한 기술과 함께, 가까운 미래에 차세대 유연/신축성 소자를 위한 높은 수율, 높은 해상도, 높은 성능을 가지는 단일벽 탄소나노튜브 어레이를 롤투롤 방식의 공정 기법으로 형성하는 것에 대한 지침을 제공해줄 수 있으며, 결과적으로 차세대 유연 응용 전자 소자 구현에 큰 기여를 할 수 있을 것으로 기대된다.Chapter 1. Introduction 1 1.1. Solution-processed Thin-film Transistors 1 1.2. Solution-processed Single-walled Carbon Nanotube Transistor 5 1.2.1. Semiconducting Single-walled Carbon Nanotube 5 1.2.2. Various Deposition Methods of Semiconducting SWCNTs with Solution-process 9 1.2.3. Main Issues of Direct Dipping Methods 12 1.3. Organization of this Dissertation 14 Reference 18 Chapter 2. Multi-dipping Technique of Semiconducting Single-walled Carbon Nanotubes for Rapid Fabrication and Performance Improvement of Solution-processed SWCNT TFTs 25 2.1. Introduction 25 2.2. Experimental Methods 29 2.2.1. Fabrication Process 29 2.2.2. Measurement Details 30 2.3. Results and Discussion 32 2.3.1. Comparision of Fabrication Time and Electrical Performances of SWCNT TFT 32 2.3.2. Mechanisms of SWCNT Network Formation 36 2.3.3. Channel Morphology 41 2.4. Chapter Summary 45 Reference 46 Chapter 3. Self-patterning Technique of Semiconducting SWCNT based on Inkjet-printing of Surface Treatment Material 49 3.1. Introduction 49 3.2. Experimental Methods 51 3.2.1. Fabrication Process 51 3.2.2. Measurement Details 52 3.3. Results and Discussions 54 3.3.1. Optimization of Printing Conditions of PLL 54 3.3.2. SEM analysis of Successful Patterning of SWCNT 58 3.3.3. Electrical Characteristics 59 3.3.4. Two Main Parameters for Inkjet-printing of PLL 61 3.3.4.1. Effect of Water-stain of PLL 61 3.3.4.2. Effect of Pattern Size of PLL 62 3.3.5. Array Implementation 65 3.4. Chapter Summary 67 Reference 68 Chapter 4. Fast and Self-patterning Technique of Semiconducting SWCNT for High-throughput and High-resolution Solution-processed TFT 70 4.1. Introduction 70 4.2. Verifying Large-area Scalability of Two Techniques for implementing SWCNT TFTs array 73 4.2.1. Fabrication Process 73 4.2.2. Electrical Characteristics 74 4.2.3. Sub-chapter Summary 78 4.3. Verifying Micro-patternability of Two Techniques for implementing SWCNT TFTs array 79 4.3.1. Concept of High-resolution and EHD printing technique 79 4.3.2. Optimization of Each Layer of TFTs with EHD printing 81 4.3.2.1. Electrode 85 4.3.2.2. Dielectric 87 4.3.2.3. Surface Treatment Materials 89 4.3.3. All-EHD-printed SWCNT TFT with Two Techniques 94 4.3.3.1. Fabrication Process 94 4.3.3.2. Electrical characteristics 96 4.3.4. Sub-chapter Summary 98 4.4. Chapter Summary 101 Reference 102 Chapter 5. Conclusion 105 5.1. Summary 105 5.2. Limitations and Related Works 108 5.2.1. Detailed Network Analysis of Multi-dipping Technique 108 5.2.2. Reliablilty and Encapsulation for All-EHD-printed TFT 112 5.3. Recommendation for Future Researches 114 Reference 117 Appendix 119 Publication List 120 Abstract in Korean 125Docto

Suspicious thyroid nodules 4 cm require a diagnostic lobectomy regardless of their benign fine needle aspiration results

Background/objective: The diagnostic accuracy of fine needle aspiration biopsy (FNAB) seems limited in large thyroid nodules with Bethesda Cat. 2 result. We aimed to determine the incidence of carcinoma with benign cytology and the reason for the high false-positive rate in thyroid nodules ≥4 cm. Methods: The records of 103 patients with thyroid nodules ≥4 cm with preoperative cytological diagnosis of Bethesda Cat. 2 who underwent thyroidectomy were consecutively reviewed. Characteristics between patients with malignant vs. benign pathology were compared. Results: Forty patients (38.8%) had malignancy. Malignancy was subclassified into follicular variant of papillary thyroid carcinoma (43%), minimally invasive follicular thyroid carcinoma (20.0%), and minimally invasive Hurthle cell thyroid carcinoma (10.9%). Patients with malignant cytology had significantly more suspicious ultrasound findings than those with benign cytology (p = 0.001). Conclusions: Preoperative FNAB showed high false-negative rates in patients with thyroid nodules ≥4 cm with benign cytology. These nodules have a high malignancy rate with suspicious ultrasound findings.ope

Diagnostic Thyroidectomy May Be Preferable in Patients With Suspicious Ultrasonography Features After Cytopathology Diagnosis of AUS/FLUS in the Bethesda System

Atypia/follicular lesion of undetermined significance (AUS/FLUS) is a new category in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) for which repeat fine-needle aspiration cytology (FNAC) is recommended. The aim of this study was to identify specific ultrasonography and clinical predictors of malignancy in a subset of thyroid nodules associated with cytology diagnoses of AUS/FLUS.Between January 2011 and December 2102, 5440 patients underwent thyroid surgery at our institution. Of these, 213 patients were diagnosed AUS/FLUS at the preoperative cytopathology diagnosis. The frequency of FNAC and ultrasonography images was compared between patients with cancerous and benign tumors based on their final pathology.Of the 213 patients, 158 (74.2%) were diagnosed with thyroid carcinoma in their final pathology reports. In univariate and multivariate analyses, the frequency of FNAC was not significantly correlated with the cancer diagnosis. Hypoechogenicity (odds ratio 2.521, P = 0.007) and microcalcification (odds ratio 3.247, P = 0.005) were statistically correlated with cancer risk.Although AUS/FLUS in cytopathology is recommended for repeating FNAC in BSRTC, we proposed that thyroid nodules with ultrasonography findings that suggest the possibility of cancer should undergo thyroidectomy with diagnostic intent.ope

Potential anti-cancer effect of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a novel histone deacetylase inhibitor, for the treatment of thyroid cancer.

BACKGROUND: Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. METHODS: Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). RESULTS: Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase activation were observed both in vitro and in vivo. HNHA increased Ca(2+) release from the ER to the cytoplasm. ER stress-dependent apoptosis was induced by HNHA, suggesting that it induced caspase-dependent apoptotic cell death in PTC and ATC. PTC and ATC xenograft studies demonstrated that the antitumor and pro-apoptotic effects of HNHA were greater than those of the established HDAC inhibitors. These HNHA activities reflected its induction of caspase-dependent and ER stress-dependent apoptosis on thyroid cancer cells. CONCLUSIONS: The present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.ope

Synergistic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide and Sorafenib Against Cancer Stem Cells, Anaplastic Thyroid Cancer

Anaplastic thyroid carcinoma (ATC) although rare is the most deadly form of thyroid cancer. The fatality rate for ATC is high-pitched, the survival rate at 1 year after diagnosis is <20%. Control of ATC is severely hard and widespread with unpredictability. We Previous proved that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. Herein, the goal of this study was to investigate the anti-tumor activities of a HDAC inhibitor, HNHA alone and in combination with sorafenib in ATC cells in vitro and in vivo and to explore its effects on apoptotic cell death pathways. Three ATC cell lines were exposed to sorafenib in the presence or absence of HNHA, and cell viability was determined by MTT assay. Effects of combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell lines xenograft model was used to examine the anti-tumor activity in vivo. Our data showed that HNHA and sorafenib synergistically decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as proved by the cleavage of caspase-3 and DNA fragmentation. HNHA and sorafenib combination was reduced anti-apoptotic factor in ATC. Thus, combination therapy with HNHA and sorafenib significantly decreased vessel density, and most significantly reduced tumor volume and increased survival in ATC xenografts. These results propose that HNHA in combination with sorafenib has significant anti-cancer activity in preclinical models, potentially suggesting a new clinical approach for patients of advanced thyroid cancer type.ope

Anti-adhesive Agent (Guardix-SGⓇ) Does Not Influence the Drainage Volume after Thyroid Cancer Surgery

Purpose: This study was conducted to investigate whether the use of HA-CMC solution in thyroid surgery influences drainage amount and hospital stay. Methods: Between November 2012 and December 12, 147 patients with thyroid cancer who underwent total thyroidectomy with central compartment neck dissection were analyzed retrospectively. The patients were divided into four groups; those with or without HA-CMC solution application and high or low output drainage. Results: There were no differences in hospital stay and mean total drainage between the with and without HA-CMC solution application groups (P=0.230, P=0.732). The mean hospital stay was 2.2±0.4 days for the low output of drainage group and 3.1±0.6 days for the high output drainage group (P＜0.001). There was no significant difference in the use of HA-CMC solution (41.1% vs. 56.8%, P=0.070). Conclusion: The use of HA-CMC solution in thyroid cancer surgery might not increase drainage amount and make hospital stay longer.ope

Assessing dentist requirements to meet the dental needs of the Korean population

보건학과/박사[한글] 국민의 치과 의료서비스에 대한 필요를 토대로 치과의사 인력규모를 알아보고자 2000년도 국민구강건강실태조사에 근거하여 유치, 영구치, 의치치료, 치주치료,악관절치료 등에 대한 연령별, 성별 분석을 시행하였다. 또한 각 진료에 필요한 시술별 소요시간을 얻어내어 치과 의료서비스에 필요한 총 시간을 구하였고, 치과의사의 진료가능 시간 등 평균 노동력을 이용하여 인력규모를 제시하였다.그 결과는 다음과 같다.첫째, 2000년 자료를 근거로 유치 치료에 필요한 진료시간은 187,605,099분이고,영구치는 2,161,448,285분, 의치치료는 1,446,274,466분, 치주치료는 493,046,960분,악관절치료는 211,762,441분으로 총 4,500,137,251분의 진료시간이 필요하다.둘째, 2010년 유치 치료에 필요한 진료시간은 2000년에 비해 23% 감소한144,311,797분이며, 영구치는 10% 증가한 2,386,361,332분, 의치치료는 35% 증가한1,959,470,543분, 치주치료는 29% 증가한 637,054,475분, 악관절치료는 1% 증가한214,319,626분의 진료시간이 요구되었다.셋째, 필요 중심으로 본 치과의사수는 2000년과 비교할 때 2010년에 19% 정도증가할 것으로 예상되었다.넷째, 미국, 영국, 호주의 치과인력제도를 적용하여 필요 중심으로 본 치과의사인력규모를 살펴보면 2010년 미국은 한국과 같은 결과이나, 호주제도는 6.3% 감소, 영국제도는 35.7% 감소가 가능한 것을 알 수 있었다.이상의 결과를 볼 때, 2000년과 비교하여 2010년에는 필요중심의 치과의사는약 19% 증가가 예상되나 공급측면에서의 치과의사 증가율은 이보다 2.1-2.4배 높은 40-46% 로 알려져 향후 공급과잉 가능성이 큰 것을 알 수 있다.또한 호주와 영국 등과 같이 치과지원인력의 활용도를 높이면 치과의사의 양적 요구 또한 큰 폭으로 줄어들게 되므로 향후 치과의사 인력규모 결정시 위임범위를 함께 고려해야 한다. [영문] Decision makers in the areas of dental health policy, resource allocation, anddental health manpower requirements rely implicitly on estimations of dentaltreatment needs on which to base their forecasts. In previous decades, severalresearches, symposia proceedings and reports which have been focusing on thedemand of dental health services and supply of dentists in Korea could notgive relevant information to the decision makers. Therefore, to provide useful information, dentist requirements to meet theneeds of the Korean population based on epidemiological data of dental healthin 2000, this study was conducted.The results were as follows;1. Restorative treatment needs of primary teeth in 2000 were 187,605,099minutes, permanent teeth were 2,161,448,285, prothodontic needs 1,446274,466,periodontal needs 493,046,960, and TMJ treatment needs 211,762,441. Totaltreatment needs were 4,500,137,251 minutes in 2000.- 56 -2. Treatment needs of primary teeth in 2010 predict 23% reduction.However, needs of permanent teeth would be increased by 10%, prothodonticneeds 35%, periodontal needs 29%, and TMJ treatment needs 1%. The trend isdriven by the demographic changes which are the increase in the number ofdentate older cohorts.3. The estimated dentists based on treatment need in 2010 would beincreased by 19% in contrast with year 2000.4. Year 2010, the estimated dentists based on the Australian dentalmanpower system would be decreased by 6.3%. Based on the British dentalmanpower system, however, the forecasted dentists would be decreased by35.7% in contrast with the Korean dental manpower system.In conclusion, it would seem that the dental policy makers in planning forthe future dentists should pay particular attention to the demographic changesin 2010 or over the next 20 to 30 years, and to viability of adjusting thesupply of dentists not only by reduction in enrollment of dental students butalso by delegation to dental auxiliary personnel.ope

A Study on Factors affected to the Sustainability of Koreas Development Assistance Projects: Case Study on Projects Implemented in Nepal

본 연구는 개발원조사업의 효과성과 지원성과를 판단하는 핵심지표 중 하나로 받아들여지는 지속성(sustainability)에 영향을 미치는 요인들을 알아보고 우리나라 ODA사업에 주는 시사점을 제시하는데 초점을 두었다. 수원국의 경제적 자립이 개발원조의 궁극적 목표라고 할 때 원조가 종료된 후에도 제공된 시설과 설비가 일정기간 계속적으로 운영 및 활용되고 있는지의 여부는 사업의 효과성 뿐 아니라 성패를 결정하는 기준이라고도 할 수 있다. 다양한 연구와 조사에 의해 국제적 원조규범으로 인정받고 있는 지속성 향상을 위한 고려들로는, 현지 수요와 환경에 대한 정확한 이해, 수혜자의 운영역량을 고려한 사업설계 및 지속적 역량강화 지원, 재정 건전성 확보, 참여를 통한 주인의식 고취 등이다. 이러한 원칙들을 참고하여 타 공여국과 규모, 사업형태 및 방식에서 상이한 우리나라 개발원조사업들의 지속성에는 어떠한 요인들이 상대적으로 많은 영향을 미쳤는지 살펴보기 위해 네팔에 지원된 우리 사업들을 대상으로 사례조사를 실시했다. 조사결과를 통해 무엇보다 수혜자의 환경과 역량을 고려한 사업설계 및 역량강화 지원 노력이 지속성 달성에 가장 큰 기여를 한 것으로 나타났다. 이 같은 결과는 지속성 실패를 초래한 사업기획 상의 문제로 현지의 역량과 환경을 충분히 고려하지 않은 점이 제시된 것과 일관성을 가지고 있었다. 이러한 연구결과는 수원국에 지원하는 개발원조 프로젝트들 대부분이 여전히 인프라 및 설비제공 위주임에 따라 사업완료 이후 운영상의 어려움을 겪는 사례들이 늘어나고 있는 우리나라에게 교훈이 되고 있으며 국내에서 ODA사업의 지속성에 관한 논의가 더욱 확대될 필요성을 시사해 주고 있다.This study focuses on identifying the factors which affect the sustainability that are considered one of the key indicators on the effectiveness and support performance of development aid projects, and on presenting the implications to Koreas ODA projects. As the economic independence of the recipient country is the ultimate goal of the development assistance, whether the facilities provided by donors are being operated and utilized continuously during a certain period after aid termination is a criteria to decide not only the project effectiveness but also for determinant of success or failure. Some of the following factors are considered ideas for improving sustainability, which are recognized as an international assistance standards based on various studies and investigations; accurate understanding on local demands and the environment, support for project design considering recipients operational ability and ongoing capacity improvement, securing financial soundness and boosting the sense of ownership through participation and so on. As referred to these factors, the study conducted a case study of our projects in Nepal to see what factors had a relatively large impact on the sustainability of the project regarding other donors and its size of project, project model and its methods. The results of case studies showed that the achievement of the sustainability was the most contributed by the project design considering recipients environment and ability or the effort to enhance capabilities. The results were consistent with the suggestion that local capabilities and environment were not considered sufficiently due to issues on the project planning step that resulted in failure to sustain the project. These findings are a lesson for Korea which is suffering from a growing number of operational difficulties after the project completes, as most of the development aid projects for the recipient country by Korea are still focused on providing infrastructure and facilities. This indicates the necessity for more discussions on the sustainability of ODA projects in Korea

척추 추간판과 종판에 있어서 pamidronate의 효과

Dept. of Medicine/석사[한글] N-containing bisphosphonate는 파골세포의 세포 고사(apoptosis)를 유도하여 파골세포의 숫자를 감소하는 약제로 널리 알려져 왔다. bisphosphonate는 골 흡수를 억제하는 강력한 억제제로서, 폐경 후 생기는 골다공증, Paget 병, 골종양, 그리고 금속성 이식물를 사용하였을 때 발생하는 osteolysis 등의 파골세포 기능 항진으로 인한 경우에 널리 이용되고 있다. 또한 관절염에 있어서는 type 2 collagen의 분해를 억제하고, 부분적으로 연골을 보호하는 기능도 있음이 알려져 왔다. 척추 종판의 경화는 추간판으로의 영양 결손을 유발하며, 이는 추간판 퇴행의 원인이 된다. Bisphosphonate가 강한 골 흡수 억제능과 연골 보호능이 있다는 사실을 종합하였을 때, 이러한 약제의 골 흡수 억제능으로 인해 척추 종판의 비후가 유발될 수 있고 한편으로는 연골 보호능으로 인한 추간판의 연골세포 유사 표현형이 유지될 수 있으리라 예상된다. 따라서 본 연구에서는 시험관내에서 bisphosphonate가 추간판세포의 대사에 미치는 영향을 살펴보고, 조직학적으로 척추 종판과 추간판에 미치는 영향을 살펴보았다. 추간판 조직은 4명의 환자로부터 획득하였으며, 단계적 효소처리를 하였으며, 2세대bisphosphonate인 pamidronate의 영향을 시험관내에서 확인하고자, 추간판세포를 alginate bead를 이용한 삼차원 배양을 실시하였다. 삼차원 배양 중인 추간판 세포에 pamidronate의 농도가 10-9, 10-6, 10-3M이 되도록 각각 처리한 후, 세포 증식에 따른 DNA 합성을 알아보기 위해 [3H]-Thymidine incorporation을 실시하였고, 신생 proteoglycan 합성을 확인하고자 [35S]-Sulfate incorporation을 실시하였다. Collagen type 1, collagen type 2, 그리고 aggrecan유전자에 대한 mRNA 발현을 확인하고자 RT-PCR을 시행 하였다. 조직학적으로 pamidronate의 척추체에 미치는 영향을 확인하고자, 24마리의 C57 BL/6 mouse를 이용하여, pamidronate를 매주 정맥 주사하였으며, 실험군은 대조군, 저용량(30ug/kg), 고용량(90ug/kg)군으로 나누고, 투여 시작 후 5주와 12주에 각각 쥐를 희생하여 척추체를 획득하였다. 획득한 조직은 H&E 염색, Safranin-O 염색 그리고 TUNEL assay를 실시하였고, 형태계측학적 자료는 Image analyzing system을 이용하여 분석하였다. 시험관 내에서 pamidronate를 추간판세포에 농도별로 처리한 결과, 대조군과 비교하여 세포증식에 있어서 의미 있는 변화는 관찰되지 않았으나, 신생 proteoglycan의 합성은 대조군과 비교하여 저농도인 10-9M의 농도에서는 40%의 증가를 보였다. RT-PCR에 대한 densitometric assay에서는, 대조군과 비교해서 type 1 collagen, type 2 collagen 그리고 aggrecan의 mRNA 발현이 통계상으로 의미 있는 결과는 관찰되지 않았다. 12주 동안 매주 과용량의 pamidronate를 투여한 실험동물에서 종판의 두께는 증가하였으나, 대조군과 비교하여 5주와 12주째 저용량과 고용량 군에서의 수핵부의 괴사나 섬유륜부의 이상, 추간판 전체의 균열과 같은 특이한 변화는 없었다. TUNEL assay 결과에서도 고사된 세포에 대한 양성 반응은 관찰 할 수 없었다. 결론적으로, 제2세대 bisphosphonate인 pamidronate는 시험관 내에서 추간판세포에 대해서는 비교적 안전하며, 저용량 처리시에는 proteoglycan 합성이 촉진되었고, 세포표현형의 변화도 없음을 확인하였다. 실험동물에서도 pamidronate를 장기간 과용량 투여하였을 시 퇴행의 변화 없이 추간판 높이가 안정되게 유지되었다. [영문]It has long been known that N-containing bisphosphonates (BPs) can reduce osteoclast number by inducing apoptotic cell death in osteoclasts. As potent inhibitors of bone resorption, they are widely used for the treatment of bone disorders that are due to increased osteoclast activity i.e. postmenopausal osteoporosis, Paget’s disease, tumoral bone disease, and particle induced osteolysis around metal implant. BPs also decrease breakdown of type II collagen and exhibit partial chondroprotective effect in a rabbit model of inflammatory arthritis. These findings support the fact that BPs have a chondroprotective effect. Nutritional deprivation caused by sclerosis of vertebral end plate provides, in part, a mechanism of intervertebral disc (IVD) degeneration. The fact that BPs have a powerful antiresorptive effect and chondroprotective effect prompts a research for the sum effect of BPs on IVDs since antiresorptive action can cause hypertrophy of endplate while chondroprotective effect can maintain chondrogenic phenotype of IVDs. Accordingly, the purposes of this experimental study were, firstly, demonstrate the effect of pamidronate, second generation N-containing BPs, on in vitro metabolism of IVD cells and secondly, the effect of pamidronate on histologic changes of endplate and IVD. Lumbar IVD tissues were obtained from four patients and digested and cultured in three dimensional alginate beads to validate in vitro effect of N-containing second generation pamidronate. Twenty-four mice (C57BL/6) were utilized to test in vivo effect of pamidronate. Various doses of pamidronate (10-9, 10-6, 10-3 M) were administered to human IVD cultures. 3H-Thymidine for DNA synthesis and 35S-Sulfate incorporation for proteoglycan synthesis were performed. Reverse transcription polymerase chain reaction for mRNA expression of collagen type I, collagen type II, and aggrecan was done. For in vivo test, high (90ug/kg) and low doses (30ug kg) of pamidronate were injected intravenously to mice weekly for 5 weeks to 12 weeks. Treatment with normal saline served as control. Hematoxylin-Eosin stain, Safranin-O stain, and TUNEL assay were performed. Histomorphometric data were also collected. Human IVD cell culture in three dimensional alginate beads with various concentrations of pamidronate (10-9, 10-6, 10-3 M) showed no significant increase in DNA synthesis compared to control culture. Human IVD cell showed significant increase in proteoglycan synthesis, 40% increase with a dose of 10-9 M pamidronate (p<0.05), compared to control culture. In densitometric assay of reverse transcription-polymerase chain reaction, human IVD cell cultures showed no statistically significant changes in mRNA expression of type I collagen, type II collagen, and aggrecan compared to control. There was significant increase in thickness of endplate in animal with high dose pamidronate for 12 weeks after weekly injection. Moreover, there were no significant changes in nucleus and annulus such as necrosis and hyalinization of nucleus, disturbance of circular pattern of annulus, and cleft in nucleus and annulus in low dose and high dose group and in 5 weeks and 12 weeks follow up group, compared to control animals. There was no significant increase in TUNEL positive cells in endplate, nucleus, and annulus of IVD in experimental group compared to control. In conclusion, pamidronate, N-containing second generation BPs, was safe in vitro metabolism of IVD and stimulated proteoglycan synthesis in low dose, and maintained chondrogenic phenotype. Also long term high dose treatment of pamidronate was also safe to IVD maintaining disc height without evidence of degeneration.ope

계몽의 선교사들 : 북부위원회와 1920~1930년대 소련의 시베리아 북부 토착민 정책

학위논문(석사) --서울대학교 대학원 :서양사학과,2008.Maste