Developement of inducible siRNA expression and delivery system

조한길 서울시립대학교 2004 국내박사

소아 급성림프모구백혈병에서 Thiopurine methyltransferase의 유전자 다형성

조한길 전남대학교 대학원 2008 국내석사

목적: 소아 급성림프모구백혈병의 치료에 6-mercaptopurine(6-MP)은 유지요법의 일환으로 매우 중요한 약물이다. Thiopurine methyltransferase (TPMT)의 활성이 낮은 경우 6-MP의 대사물질이 축적되어 부작용의 발생이 증가할 것으로 추측할 수 있다. TPMT 활성도는 유전자형과 밀접한 관계가 있다고 알려져 있다. 이에 저자는 한국인 소아 급성림프모구백혈병 환자에서 TPMT의 유전자형을 분석하고 약제 부작용을 조사하였다. 방법: 2007년 5월부터 2007년 8월까지 화순전남대병원 소아과에서 급성림프모구 백혈병으로 진단되어 항암치료를 받고 있는 환자 중 연구에 필요한 채혈에 동의한 44명의 환자를 대상으로 하였다. 대상 환자들에게서 TPMT 유전자형 분석을 시행하였고, 유지요법 시행 중인 40명을 대상으로 TPMT 유전자형에 따른 부작용 발생을 비교하였다. 결과: TPMT 유전자형은 43명에서 TPMT*1/*1로 조사되었고 1명만이 변이 유전자의 이형 접합체로 TPMT*1/*3C를 나타내었다. 유지요법을 시행한 40명의 환아에서 6-MP의 용량은 TPMT*1/*1 유전자형을 갖는 환자에서는 중앙값 13%로 감량되었고 TPMT*1/*3C 1례에서 8%의 감량을 보였다. 그리고, TPMT*1/*1 유전자형을 갖는 환자 중 11명이 평균 2.3회의 간독성을 나타냈고, 18명이 평균 2.2회의 조혈계 독성을 나타냈다. TPMT*1/*3C 유전자형을 갖는 경우에 간독성이 2회, 조혈계 독성이 2회 발생하였다. 결론: 급성림프모구백혈병 환자 44명 중 1명에서 TPMT 변이 유전자형을 발견하였으나, 부작용과의 연관성이 있음을 명확히 설명하기는 어려웠다. 우리나라에서도 TPMT 유전형에 대한 대단위의 연구를 통해 각각의 유전형에 따른 6-MP 치료 용량의 기준을 확립할 필요가 있을 것으로 생각된다. Purpose: 6-mercaptopurine (6-MP) is a very important drug in pediatric patients for the maintenance treatment of acute lymphoblastic leukemia (ALL). 6-MP is catabolized by thiopurine methyltransferase (TPMT). TPMT activity, one of the related factors for toxicity or efficacy of 6-MP, is determined by genetic polymorphisms, The aim of this study is to screen TPMT genetic polymorphism in Korean pediatric ALL. Methods: The study included 44 children with ALL who were treated between May, 2007 and August, 2007 at Chonnam National University Hwasun Hospital. TPMT genotypes were analyzed by using polymerase chain reaction and gene sequencing from peripheral blood white blood cell. Results: Most of the patients had homozygous wild type (43/44, 97.7%), while only one (2.3%) had heterozygous mutant type. The % of dose reduction of 6-MP during maintenance chemotherapy was not different between wild type TPMT*1/*1 (n=39) and TPMT*1/*3C variant (n=1). Thirty three of 39 TPMT*1/*1 type experienced adverse effects such as hepatotoxicity (n=11, median frequency: 2.3) and hematopoietic toxicity (n=18, median frequency: 2.2). One TPMT*1/*3C variant experienced 2 times of hepatotoxicity and hematopoietic toxicity, respectively. Conclusions: The TPMT*1/*3C variant was detected in one patient among 44 cases with ALL. Many others with wild type TPMT also could not tolerate planned 6-MP. Large study for TPMT polymorphism seems to be necessary for the establishment of standard 6-MP dosage by TPMT genotypes in Korea.

경기도에서 분리한 Norovirus의 분자역학적 연구 및 향상된 검출법 개발

조한길 서울시립대학교 일반대학원 2014 국내박사

본 연구는 경기도 내 노로바이러스 감염증의 정확한 발생률 파악, 유전적 다양성 및 역학적 특징 분석과 이를 뒷받침할 수 있는 향상된 검출법 개발 등을 통하여, 노로바이러스의 감염 확산을 차단할 수 있는 백신 개발과 예방 정책 수립에 필요한 기초자료를 제공하고자 수행되었다. 1. 개별발생에서의 노로바이러스 GII.4 변이주 출현 2006년부터 2013년의 연구 기간 중, 노로바이러스GII.4 유전형은 약 60%의 노로바이러스 감염에 관여하고 있었으며, 5가지의 변이주 즉, GII.4-2006a, -2006b, -2007, -2009, -2012 변이주들이 확인되었다. 이와 같은 GII.4 변이주들의 빈번한 출현과 확산은 전체적인 노로바이러스 유행 수준에 큰 영향을 주고 있었다. 따라서, GII.4 유전형은 가장 유력한 백신 후보주로 예상되며, 앞으로 새로운 GII.4 변이주 출현에 대한 감시 체계가 강화되어야 할 것이다. 2. 집단발생에서의 노로바이러스의 역학적 특징과 GII.4 변이주 동 연구 기간 중, 경기도 내에서 발생한 318건의 집단장염 발생사례를 분석한 결과, 노로바이러스는 102(32.1%)건에서 확인되었다. 역학조사 결과, 학생 연령층(47.1%) 에서 가장 많이 관찰되었다. 노로바이러스 GII.4 유전형은 49건에서 확인되었으며, 4 가지의 GII.4변이주(2006b, 2007, 2009, 2012)들이 확인되었다. GII.4 변이주의 빈번한 출현과 확산은 전체적인 노로바이러스 집단장염 발생의 증가에 영향을 주고 있었다. 노로바이러스 관련 집단장염 발생을 차단하기 위해서는, 근본적인 오염원을 신속히 파악할 수 있는 전반적인 역학조사 체계의 강화가 필요하다. 3. 노로바이러스 검출을 위한 향상된 real-time RT-PCR법의 개발 기존에 보고된 real-time RT-PCR법을 보완하여, 개선된 DNA probe를 제작하였다. 확보된 11가지 노로바이러스 GI 유전형들을 이용하여 검증한 결과, 개선된 시험법은 11가지의 GI유전형을 검출한 반면, 기존 시험법은 7가지의 GI 유전형만을 검출하였다. 또한, 개선된 시험법은 높은 민감도를 보였으며, 지하수를 비롯한 물 검체에서도 상대적으로 높은 노로바이러스 검출률을 보였다. 향상된 시험법은 노로바이러스가 미량 존재하는 물을 비롯한 환경 검체에 적용함으로써, 노로바이러스 오염원 규명에 기여할 수 있을 거라 예상한다. Considering targeted interventions, such as vaccines and antiviral-drugs, for reducing the degree of NoV infections, precise prevalence of NoVs and genetic features based on the relevant diagnostic methods are inevitable background data. NoVs was the most prevalent viral agent for sporadic acute gastroenteritis (AGE) in Gyeonggi during the 2006 to 2013. NoV GII.4 was the most prevalent genotype and five GII.4 variants were successively identified; 2006a, 2006b, 2007, 2009 and 2012. These frequent emergence and rapid spread of GII.4 variants significantly affect the magnitude of seasonal sporadic NoV infections. In the absence of suitable vaccines, close monitoring system for GII.4 variants should be intensified. Molecular and epidemiological investigation was performed with 318 AGE outbreaks reported during the 2006 to 2013. NoVs were associated with 102(32.1%) outbreaks. Epidemiological data revealed that NoV outbreaks were mostly detected in student group. NoV GII.4 strains were predominantly associated with 49(57.6%) of NoV GII outbreaks. Four GII.4 variants, GII.4-2006b, -2007, -2009 and 2012, were serially emerged and differently contributed to NoV outbreak activity. To prevent further outbreaks, epidemiological investigations should be intensified to track the source of NoV contamination. The modified TaqMan probes were developed and evaluated with 11 genotypes of NoV genogroup(G)I strains . The modified TaqMan assay revealed broader and more-sensitive results in detection of NoV GI strains. The improved TaqMan assay detected all 11 genotypes of NoV GI, whereas the conventional TaqMan assay detected 7 genotypes of NoV GI. The modified TaqMan assay was successfully applied to water samples. These improvements of TaqMan assay would be helpful to researcher in public health and to control waterborne NoVs-associated outbreaks.

戰後 日本 防衛政策의 分析과 軍事力 增强에 關한 硏究 : 新防衛政策에 있어서 軍事力의 役割

조한길 忠南大學校 2003 국내박사

As for the dissertation you have seen, it was deducing/deriving Japan's defense policy, military strength's concept and development after the Pacific War and what is to be the role of its military forces/strength in post Cold War world. The research subjects time period is from Japan's defeat in 1945 until the present year 2003. Japan is geographically an island nation and as for threats from foreign countries, while it possesses the advantage of being relatively free of security issues, historically it has competed with China for area dominance, and as for Russia, has generally maintained a hostile relationship. As for Japan's imperialistic past, from the time of Pacific War defeat and the occupation of the Japanese homeland by the United States, it was transformed into a democratic nation pursuing financial freedom and a market economy. As for the U.S., which was the nation occupying Japan's homeland, it had the desire of making Japan a nation that was demilitarized, but as the Cold War with the Soviet Union was intensifying, the U.S. decided to make Japan into an ally and allowed it to maintain its military. Article 9 of the Constitution in 1954 established both a defense agency and the Self Defense Force and began the construction of a military force and developed a national defense policy. In violation of its constitution, the role of Japan's military during the Cold War era started irregularly and emphasized a defensive role in opposition to the Soviet threat from the start. Especially from the middle 1970's Soviet naval power was the most powerful in the East China Sea and the Ohkhotsk Sea and encroached on Japan's sovereign territory and penetrated into the Eastern Sea. It also threatened the sea lines of communication which were the nations lifeline while compelling reinforcement of Japan's military strength. As for Japan, from the 1980's onward, it promoted a full scale reinforcement of its military strength and committed 32 trillions and 450 billions yen during a ten year period to its defense funding from its vast economic power and used as its moral justification its opposition to the Soviet air and naval threat. In the early stages of the Cold War era, Japan pursued a small military force and a passive defense policy, but during the 1980's Japan moved to reinforce its military strength, while in the northern area it opposed the Soviet's conventional military strength and in the south it had to maintain expeditionary military strength so that it could solely defend all by itself the East Sea's 1000 miles Sea Lane standard. During the 1990's the Soviet Federation/Confederation collapsed and the Cold War ended. As for the post-Cold War world, the U.S. reinforced its standing in international politics and facilitated the spread of the U.S,'s national ideology worldwide. The enemy that we called the Soviet Union became extinct and, accordingly the U.S- Japanese security alliance's basic objective for existing was said to be lost and had to be re-evaluated. Domestically it accelerated the Conservative Left in getting out of difficulty from the mental restraint of its defeat. With the disappearance of the Soviet Union as a main enemy, the PRC emerged as a new security threat, and North Korea has under taken actions dangerous enough to make the North-East Asia security environment unstable. Accordingly, it was unavoidable for Japan to continue to benefit from security free-riding from the U.S.- Japan concluded that the security free-riding was helpful for the Japanese national interests. This also led to further consolidation of the US-Korea alliance which was reflected in the revised version of Japanese defense plan-1995 and a revised U-5.-Japanese mutual defense in 1997. There are three main points underlying the new defence plan and the New Guideline. First, the pursuit of the extant exclusively defense oriented and basic defense forces concept. Second, consolidation of the US-Japan security alliance. Third, the enlarging the role of military preparedness. Therefore the role of JSDF under the new defense policy seeks a solidification of its role for national policy and national defense : to maintain the roles of attack and compulsion by military forces, sustaining the role of war deterrence by military forces. Roles that cannot be fulfilled by the JSDF alone can be supplemented by US forces through combined operations. In conclusion, Japan needs total security because of the vulnerability caused by the small land area, large population, scarce resources, SLOC security, etc. In this context, it can be said that the exclusive defense only and passive role of JSDF the contributed to the safety and prosperity of Japan and the safety of neighboring countries' security. Therefore Japan is expected to continue the national strategy for total security even during the post-cold era, and roles of the JSDF will be further enlarged along with the strengthening of the US-Japan security alliance and military forces. The PRC is now rapidly emerging in the 21s1 century in North-East Asia. Concerned North-East Asia Countries should form a multilateral security system to build confidence and to enhance regional peace and safety. JSDF is expected to play a positive role in building this confidence and regional peace using its own military forces in a manner that is not competitive or antagonistic toward its neighboring countries' armed forces.

金融環境 變化에 따른 農業金融의 發展方向

조한길 고려대학교 1993 국내석사

淸日戰爭時 日本의 外交政策決定 過程에 관한 硏究 : Richard C. Snyder의 分析 모델을 基準으로

조한길 慶南大學校 大學院 1995 국내석사

Development of the Autonomous Underwater Vehicle Cyclops and Control System Design : 수중로봇 싸이클롭스의 개발과 제어 시스템 설계

조한길 포항공과대학교 일반대학원 2014 국내석사

We developed a novel hovering-type autonomous underwater vehicle (AUV) named `Cyclops' for precise observation. The concepts for the AUV are high performance maneuverability, expandability and easy maintenance. To achieve the concepts, we designed symmetric hull of the AUV, propulsion system, communication system and electric devices, and developed operating software to control the AUV. For the safety, we analyze structural rigidity using FEM. In terms of control of the AUV, we proposed an integral sliding mode controller (ISMC) and a second-order sliding mode controller (2-SMC) to stabilize an autonomous underwater vehicle which suffers from unknown disturbances. The ISMC compensates for uncertain hydrodynamics uncertainties and rejects the effect of unknown disturbances such as waves, tides, currents and buoyancy. The ISMC is comprised of an equivalent controller and a switching controller to suppress the parameter uncertainties and external disturbances. The structure of 2-SMC is similar to the ISMC. The difference lies in that it increases the order of sliding surface, thereby reducing the chattering phenomenon. The closed loop systems for each controller are exponentially stable in the presence of hydrodynamics and unknown disturbances. We tested the proposed methods using computer simulation of an AUV model and a real AUV. We compared the performance of proposed controllers without and with switching controller in the simulation and experimental results, which confirmed that the methods improve the trajectory tracking performance against external disturbances. Finally, we conducted sea-trial to check the whole AUV systems. Through sea-trial, we validate hull structure safety, propulsion system, communication system and control system.

고령자를 위한 차세대 스마트홈 서비스 로드맵 제시에 관한 연구

조한길 단국대학교 2008 국내석사

한국 사회는 빠른 속도로 고령화 사회에 진입하였다. 특히, 2016년에는 고령자의 인구 비가 유년 인구보다 많아져서 2020년에서 125.9%로 전망하고 있다. 또한 이전 고령자에 비하여 현재 고령자들은 의식을 전환하여 단순히 고령자를 위한 복지 및 요양시설보다는 거주하고 있는 지역에서 계속적으로 일반인과 함께 생활하기를 원하고 있다. 이러한 상황 속에서 우리나라에서는 2000년대 초반부터 이런 고령자 사회에 대응하기 위한 하나의 솔루션으로 유비쿼터스 기반의 스마트홈에 대한 연구가 진행 중에 있다. 하지만 스마트홈에 대한 연구가 단순히 고소득층을 대상으로 개발되고, 기술 중심적으로 진행되고 있는 것에 문제점이 나타나고 있다. 특히, 스마트홈은 거주자의 신체적, 정신적 측면뿐만 아니라 생활 패턴, 가치관, 태도 등 종합적으로 반영되지 않고 있다. 따라서 초고령화 사회에 대비하기 위해서는 저소득층 고령자를 배려한 스마트홈 서비스 연구가 필수적이다. 본 연구에서는 기술 공급적 개발 연구에서 벗어나 사용자가 선호하는 요소들을 도출하여 일반인과 함께 생활할 수 있는 주변 환경 및 기반을 조성하는 것에 중점을 두고, 이론 고찰과 설문조사에 바탕을 두어, 저소득층 고령자를 고려한 차세대 스마트홈 서비스 시나리오와 로드맵을 제시하였다. 설문조사는 만 45세 ~ 64세까지의 남녀 중장년층을 대상으로 실시하여, 나타난 결과를 바탕으로 시나리오에 적용하였다. 특히 제시한 시나리오의 객관성과 대표성을 확보하기 위해 일반적인 고령자의 라이프 싸이클을 분석하고, 그것을 토대로 시나리오를 전개하였다. 시나리오의 일부분에서 스마트홈 구축을 위한 필요한 기술들을 도출하고, 그 기술의 상황을 크게 3가지인 개발 완료된 기술, 보완 및 Upgrade 필요 기술, 개발해야 할 기술로 분류하여 분석하였다. 이러한 과정을 통하여 기술적 로드맵을 개발하여 제시하였으며 다음과 같은 결론을 얻었다. Healthcare 서비스 시스템의 기술들은 총 8가지로 체성분/혈압/혈당 측정 센서, 모든 정보의 Display 화면 및 1:1 화상 시스템과 음성 시스템, 의료 기관과 연계한 변기/침대/운동기기 시스템, 119 연계 시스템과 비상상황 시 가족 통보 시스템, 통합 의료 정보 시스템이다. 이 중에서 의료 기관과 연계한 변기/침대/운동기기 시스템은 아직 개발된 기술들이 존재하고 있지 않은 기술로 향후 연구되어야 할 기술이고, 나머지 기술들은 보완이 필요한 기술들이다. Security 서비스 시스템의 기술들은 총 6가지로 조명/가스 밸브 자동 조절 시스템, 신체인식 시스템, 홈네트워크 보안 시스템, 비상호출 시스템, 유인 감시 모니터링 시스템과 CCTv 시스템이다. 이 중에서 개발이 완료된 기술로는 조명/가스 밸브 자동 조절 시스템으로 조사되었으며, 현재 보유하고 있지 않은 기술로 홈네트워크 보안 시스템은 연구 개발해야 할 기술이다. 나머지 기술들은 보완이 필요한 Upgrade 기술에 해당된다. 상기 Healthcare와 Security 서비스의 필요 요소 기술들은 2000년대 초반부터 기술 개발이 시작되어, 현재 많은 기술들이 사용되고 실생활에 적용되고 있다. 하지만 스마트홈을 구축하기 위해서는 아직 미흡한 기술들이 대부분이다. 특히, 현재 기술들은 상업적으로 상용화되어 고소득층 고령자를 대상으로 개발 완료되어 있는 상황으로 저소득층 고령자를 위한 스마트홈 구축을 위해서는 정부와의 연계가 필수적이다. 따라서 홈네트워크를 구축하는 시기로 2010년까지 개발이 미비하거나 개발해야 할 기술들은 연구 개발과 보완이 이루어져야 할 것이고, 2020년을 스마트홈의 실용화시기로 목표를 두고, 저소득층 고령자를 위한 스마트홈 구축에 더 많은 노력과 연구가 필요할 것이다. With Korea rapidly getting into an aging society, it is expected that the number of older people is higher than that of younger people in 2016, accounting for 125.9% in 2020. Moreover, unlike previous older people, current older people prefer living together with other ordinary neighbors in their local areas to being taken care of by welfare and nursing homes. Since the beginning of 2000, the research of ubiquitous-based Smart Home has been conducted in Korea in order to effectively respond to rapidly increasing aging society. Unfortunately, however this research has been targeted only towards high-income older people, mainly focusing on technology. In addition, the Smart Home under research does not consider various factors such as life style, value, attitude as well as residents' physical and mental characteristics. Therefore, in order to prepare for a super-aging society, it is essential to conduct research on Smart Home service for low-income older people. This study was intended to discover older people's favorites beyond previous researches focusing on technology-based development, ultimately establishing the ideal environment and foundation where older people enjoy their lives together with their neighbors. Furthermore, based on theory examination and survey, this study suggested next-generation Smart Home service scenario and roadmap for low-income older people. For this study, 45 ~ 64 aged males and females were surveyed and the survey result was applied to the scenario. In particular, so as to ensure objectivity and representative of the suggested scenario, life cycle of general older people was analyzed and scenario was developed on the basis of this life cycle. Technologies necessary for establishing Smart Home were extracted from a part of the scenario. Those technologies were mainly divided into three parts: technologies completely developed; technologies needed to be compensated and upgraded; and technologies needed to be developed. With the above processes, technological roadmap was developed and suggested. The result of this study can be summarized as follows: There are a total of eight healthcare service system technologies: body composition/blood pressure/blood sugar measurement sensors display screens and 1:1 video & voice systems toilets/beds/exercise machine systems associated with medical institutions 119-linked systems and emergency notification systems and integrated medical information systems. Among these technologies, toilets/beds/exercise machine systems associated with medical institutions have not yet developed and need to be studied in the future. Except for toilets/beds/exercise machine systems, other technologies need to be compensated. There are a total of 6 security service system technologies: lighting/gas valve automatic adjustment systems body recognition systems home network security systems emergency call systems manned inspection/monitoring systems and CCTV systems. Lighting/gas valve automatic adjustment systems have been already developed while home network security systems have not yet developed. The other four technologies belong to the upgrade technology which needs to be compensated. Since the beginning of 2000, technologies necessary for the above healthcare and security service have been developed and currently most of them are actually applied to our lives. However, lots of technologies are insufficient enough to be used for Smart Home. Moreover, since current technologies are commercialized and developed mainly focusing on high-income older people, strong cooperation with the Korean government is essentially required to establish innovative Smart Home for low-income older people. Therefore, insufficient technologies must be developed and updated until 2010 when home network will be finally established. With the goal of putting Smart Home to practical use in 2020, more effort and passion must be put into the establishment of Smart Home for low-income older people, and many related researches must be conducted as well.

AUV based Precise Seabed Mapping with a Wave Energy-harvesting Surface Vehicle

조한길 포항공과대학교 일반대학원 (창의IT융합공학과) 2019 국내박사

The AUVs have a wide range of applications and are being deployed for various purposes in an oceanographic survey, geoscience, military surveillance, and industrial areas. However, in most cases, the AUVs have preprogrammed a plan to follow a preset route of waypoints and there are few reasoning and adapting for changes against an unexpected situation even in case of the commercial AUVs. To reach a higher intelligence level for AUV technology, the AUVs must perceive the surroundings and infer their current states based on the perceived information. For underwater perception, vision-based sensors are widely used but have limits to use in water due to rapid wavelength-dependent attenuation of light by water. With consideration for the water turbidity, sonars are a generic solution for underwater sensing. Compared to vision-based sensors, the lack of information of sonar data is indisputable: the loss of elevation information, perceptual ambiguity, and a high proportion of outlier, which complicate sonar data processing and three-dimensional (3D) map building. Another issue on AUV exploration is about connectivity. The AUVs should be connected to a network for sharing the data obtained from onboard sensors and intervention for high-level work. Therefore the subsea data can be transmitted to the air only via a relay station on the surface such as relay buoys. To overcome the issues, we propose a sustainable connected AUV system that consists of an AUV and surface vehicle. The AUV is able to perceive the environment regardless of water turbidity. The surface vehicle has affordable electrical payload for long-range data communication and maneuvering for relocation. The two vehicles are interlinked via acoustic communication. For the perception, sonar-based mapping is proposed, and for the electrical payload of the surface vehicle, a novel wave energy harvesting device is developed. First, we present a three-dimensional (3D) mapping method in one-way rectilinear scanning with an autonomous underwater vehicle (AUV) equipped with a forward-looking sonar (FLS) and a profiling sonar (PS). Our approach is to use an additional sonar and fuse acoustic measurements provided by the two sonar sensors. The FLS has a high resolution in a horizontal scan but has an uncertainty in the vertical direction. On the other hand, the PS provides a reliable vertical profile but its beam width is extremely narrow. An initial map is generated by the FLS and refined by combining vertical scan data provided by the PS. Second, a novel surface vehicle was proposed to support a long-term survey of AUV by harvesting wave energy. We proposed a wave energy converter called the wave turbine system (WTS) and verified the feasibility of the proposed system. To verify the proposed mechanism and identify the system parameters, we developed a hydrodynamic model for the WTS and simulated its behavior and power generation capability. From the quantitative simulation, optimal system parameters were analyzed. To check the reliability of the simulation result, we carried out verification tests in a water tank, and the simulation result was verified. Finally, The hardware systems for an AUV named Cyclops and an energy-harvesting surface vehicle were developed. The proposed method is implemented in the developed system and to demonstrate the validity and effectiveness of the proposed method, we conducted a series of tests in a water tank and also at sea. The total system was integrated, and validity was demonstrated through the sea trial.