The role of thymosin β-4 in vitro and in vivo based on primary cilia formation

이재욱 세종대학교 대학원 2018 국내박사

Non-motile primary cilia are antenna-like organelles protruding from the cortical cell surface in most eukaryotic cells. And primary cilia is enriched with diverse signaling receptors and transduce signals from outside to inside. Since their diverse function and distribution, dysfunction of them results in severe developmental defects and organ homeostasis failure. Therefore, studying of primary cilia formation is important to understand pathological mechanisms of ciliopathies such as cancer and obesity. Thymosin beta-4 (Tβ4) is an actin-sequestering protein and involved in several cellular functions, such as cell migration, cell proliferation and tissue repair. Furthermore, it is over-expressed in highly invasive and aggressive cancer cells. When yeast two-hybrid screening was implemented by using Tβ4 as a bait, nephrocystin-3 (NPHP3), one of ciliary protein, was physically interacted. I examined effect of Tβ4 in vitro and in vivo on primary cilia formation and ciliopathies, especially cancer and metabolic disorders. For the first, I investigated whether Tβ4 regulates cilia formation by the association with NPHP3 in HeLa cervical cancer cells. I confirmed the direct binding of Tβ4 with NPHP3 by GST-pulldown assay and they were co-localized at the edge of cell peripheral surface. HeLa cells expressed noticeable number of primary cilia compared to that in many other cancer cells. Remarkably, inhibition of Tβ4 reduced primary cilia formation. Also, the ciliated cell number increased in Tβ4-GFP positive cells. The number of ciliated cells was reduced by the inhibition of NPHP3. In addition, the frequency of primary cilia in NPHP3-overexpressed cells was reduced by knockdown of Tβ4. In the point of molecular correlation, NPHP3 was decreased by the inhibition of Tβ4, but it was increased by Tβ4 overexpression. In contrast, Tβ4 expression was not affected by neither the interference nor overexpression of NPHP3. Taken together, the results demonstrate that primary cilium formation could be affected by Tβ4 through the regulation of NPHP3. It suggests that tumorigenesis could be associated with the perversion in Tβ4 and/or NPHP3 expression to maintain primary cilia formation normally. Reactive oxygen species (ROS) are continuously generated during metabolic process and involved in cellular signaling and homeostasis. The production of ROS is also stimulated by cellular stress, such as growth factor deprivation. Serum starvation increased total ROS level in HeLa cells. And the frequency of ciliated cells were decreased by ROS scavenger, NAC, under the serum starve condition. We examined whether ROS are associated in Tβ4-mediated primary cilia formation. Inhibition of Tβ4 reduced ROS generation whereas Tβ4 expression was not affected by serum deprivation. Also, Hydrogen peroxide (H2O2), the one of ROS, increased in serum starvation. Treatment of H2O2 increased ciliated cell number that was attenuated by catalase, the H2O2 degrading enzyme. Moreover, the serum starvation-increased H2O2 was declined by knockdown of Tβ4. The H2O2–induced ciliogenesis was also reduced by knockdown of Tβ4. These results suggest that Tβ4 could affect ciliogenesis through the generation of ROS. Based on the findings that primary cilia could be increased by Tβ4 in cancer cells, I investigated whether Tβ4-induced primary cilia leads malignant phenotypes in cancer cells. Vinblastine, an anti-tumor drug,-induced cell death decreased in serum staved HeLa cells. In contrast, Inhibition of primary cilia by ciliobrevin A (cilioA) increased vinblastine-induced cell death. Furthermore, Tβ4-overexpression reduced anti-tumor activity of vinblastine and the drug resistance was lessened by inhibition of primary cilia. These findings suggest Tβ4 could lead resistance to vinblastine via induction of primary cilia. Type2 diabetes mellitus (T2DM) is caused by genetics and/or environmental factors such as eating high-fat foods. Tβ4 has an anti-fibrotic and anti-inflammatory effect on several T2DM complications. In addition, it regulated ciliogenesis. And primary cilia is involved in regulation of energy balance and metabolic process. I investigated the effects of Tβ4 on High fat diet (HFD)-induced obesity and T2DM with the association of primary cilia in vivo. Weight increase by HFD was significantly reduced in Tβ4-transgenic mouse group compared to C57BL6 control group although food consumption was even higher in Tβ4 group. Adipose tissue amounts and adipocytes size was considerably reduced in Tβ4 group. Lower level of plasma leptin was also showed in Tβ4 group. In addition, fatty liver was noticeably inhibited in Tβ4 group. Furthermore, Tβ4 group improved glucose control and insulin sensitivity with the prevention of hyperinsulinemia. Therefore, data demonstrated Tβ4 prevented HFD-induced lipogenesis and obesity and improved glucose and insulin intolerance. Next, to see the effect of primary cilia on metabolic disorder, I treated cilioA to dampen cilia number in mouse. Weight gain, fatty liver and glucose regulation was not affected by cilioA in HFD-WT group. The lipid accumulation in adipose tissue rather slightly decreased. Nevertheless, the fasting insulin level was worsen by cilioA. Since the number of primary cilia was well maintained in HFD-Tβ4-Tg mouse compared to that in HFD-WT mouse, when the maintained primary cilia was inhibited by cilioA in HFD-Tβ4-Tg mouse, glucose intolerance and insulin sensitivity was aggravated. Taken together, Tβ4 might have anti-diabetic properties correlated with maintaining primary cilia in obese state. It suggests that Tβ4 likely be a novel restrainer of morbid obesity and T2DM caused by bad eating habits. Collectively, Tβ4 may regulate primary cilia formation through the control of NPHP3 or ROS production in HeLa cervical cancer cells. Cancer cells with primary cilia may acquire the malignant properties by showing resistance to vinblastine anticancer drugs. In addition, the expression of Tβ4 in the metabolic disorder showed the improvement effect of obesity and diabetes mellitus, which could be seen as the effect of in vivo energy and metabolism control through maintenance of primary cilia.

한국법을 준거법으로 한 선체용선계약의 법적 쟁점에 관한 비교법적 연구 -BARECON 양식을 중심으로- : -BARECON 양식을 중심으로-

이재욱 한국해양대학교 해사산업대학원 2020 국내석사

선체용선자는 선체용선계약을 통하여 선체용선기간 동안 선박소유자로부터 선박에 대한 전면적인 점유 및 지배․관리권을 넘겨받아 운용한다. 선체용선계약의 유형은 크게 운용형과 금융형 선체용선계약[예를 들면, 소유권취득조건부 선체용선계약(BBCHP)]으로 나누어 볼 수 있다. 운용형 선체용선계약은 BARECON 양식에 따라 체결되는 경우가 많다. BARECON은 선체용선계약 당사자가 계약에 적용될 준거법을 합의로 정할 수 있도록 하되, 별도의 합의가 없는 경우 영국법이 준거법이 된다고 규정한다. 한국법을 BARECON의 준거법으로 합의하는 경우, 운용형 선체용선계약은 그 법적성질이 임대차와 유사하므로 그 성질에 반하지 않는 이상 한국 민법의 임대차 규정이 준용된다. 선체용선계약은 당사자자치에 따라 규율되므로 한국 민법의 임의규정보다 BARECON 조항이 우선 적용되어 설령 임의규정과 일부 다른 내용이 있다고 하더라도 대부분의 조항에 있어서 그 해석과 법률효과에 있어서 영미법을 준거법으로 한 경우와 큰 차이는 없을 것이다. 그러나 한국 민법의 강행규정에 저촉되는 BARECON 조항은 효력이 없게 된다. 특히 민법 제627조와 제628조의 용선료 증감청구권은 강행규정으로 이에 반하여 선체용선자에게 불리한 조항은 효력이 없다. 따라서 비록 BARECON 2017 제3조 (c)항에서 선박이 용선자에게 인도된 이후에는 선박소유자의 의무는 전부 이행된 것으로 보고 그 이후에는 선체용선자가 법적 구제수단을 행사할 수 없다고 규정하고 있더라도, 선체용선자는 민법 제627조와 제628조를 근거로 용선료감액청구권을 행사할 수 있다. 선박소유자가 선박의 하자를 알면서 용선자에게 고지하지 아니한 경우에는 BARECON 2017 제3조 (c)항에도 불구하고, 민법 제584조에 따라 하자담보책임의 면제특약의 효력이 인정되지 않는다. BARECON 2017 제31조 (d)항의 도산해지조항에 따라 용선자가 도산한 경우 선박소유자는 선체용선계약을 해지하고 용선자의 영업자산인 선박에 대한 점유를 회복할 수 있다. 이 조항으로 인하여 용선자는 선박을 운용하여 이익을 얻을 수 없어 용선자의 회생이 곤란하게 되는 문제가 있다. 영국법을 준거법으로 하는 경우 도산해지조항의 효력이 인정될 가능성이 크다. 그러나 한국법을 준거법으로 한 경우 운용형 선체용선계약은 임대차의 성질을 가지므로 이를 쌍방미이행 쌍무계약으로 보아 관리인의 이행청구권을 보장하고 도산해지조항의 효력을 배제함으로써 도산절차에서의 안정성 및 용선자의 회생에 도움이 될 수 있다. 이처럼 BARECON 양식에 따른 운용형 선체용선계약을 체결하는 경우 준거법을 한국법으로 합의함으로써 도산절차에서의 안정성을 도모하고 경제사정의 변동에 따라 용선료증감청구를 할 수 있는 장점이 있다. 향후 많은 계약 당사자들이 BARECON 양식에 따른 운용형 선체용선계약의 준거법을 한국법으로 합의함으로써 이러한 장점을 활용할 수 있기를 기대한다. During the charter period the vessel shall be in full possession and at the absolute disposal for all purposes of the charterers and under their complete control in every respect. The bareboat charter can be classified into two large groups : Operating bareboat charter and Financing bareboat charter[for example, Bareboat Charter with Hire Purchase(BBCHP)]. It's very common for the parties to use the BARECON form for the operating bareboat charter. When the parties use the BARECON form, they can mutually agree the governing law and the arbitration place but they do not agree, the charter party shall be governed by and construed in accordance with English law. When the parties agree that the charter party shall be governed by and construed in accordance with Korean law, the provisions regarding leases under the Civil Act shall apply mutatis mutandis to the operating bareboat charter which is lease in nature according to Korean Law. Because the parties' intention shall prevail the optional provisions of Korean Civil Act, most of the articles of BARECON shall not be construed differently irrespective of governing laws, even though the articles are in contravention of the optional provisions of Korean Civil Act. But when some articles of BARECON are in contravention of the mandatory provisions of Korean Civil Act, the articles will be void. Especially, because the Article 627 and 628 of the Korean Civil Act are mandatory provisions, any articles of BARECON which are in contravention of the Article 627 and 628 and unfavorable to charterers shall be void. As a result, the charterers can demand a reduction of the hire on the ground of the Article 627 and 628 of the Korean Civil Act, even if BARECON 2017 article 3(c) says the delivery of the vessel by the owners and the taking over of the vessel by the charters shall constitute a full performance by the owners of all the owner's obligations under the clause, and thereafter the charterers shall not be entitled to make or assert any claim against the owners. The owners may not be relieved of liability in respect of any fact of which they were aware and nevertheless failed to disclose according to the Korean Civil Act article 584 in spite of BARECON 2017 Article 3(c). According to the Ipso Facto Clause[BARECON 2017 article 31(d)] when the charterers go bankrupt, the owners may terminate the charter party and repossess the vessel. Because of the clause, it is difficult for the charterers to make a profit by operating the vessel and to rehabilitate. When BARECON 2017 article 31(d) is governed by and construed in accordance with English law, the Ipso Facto Clause shall be in effect. But when the parties agree that article shall be governed by and construed in accordance with Korean law, the operating charter party which is lease in nature, shall be treated as the bilateral contract the parties have yet to complete performance of the contract, the custodian of the charterers has an option to terminate or require the owners to fulfill the owners' obligations. So the Ipso Facto Clause is not effective, it can help the charterer's rehabilitation. When the parties of the operating charter party agree that the charter party(BARECON form) shall be governed by and construed in accordance with Korean Law, it can help the rehabilitation of the charterers and the parties have the advantage of demanding the other party to raise or reduce the hire for the future when the economic situation changes. I wish that many parties agree the charter parties shall be governed by and construed in accordance with Korean Law and they can make good use of these advantages from now on.

間接正犯의 正犯性에 관한 연구

이재욱 숭실대학교 1997 국내석사

파워카드 기법을 사용한 스트레스 표현행동 중재가 아스퍼거 증후군 초등학생과 어머니와의 상호작용에 미치는 영향에 관한 사례 연구

이재욱 강남대학교 대학원 2010 국내석사

The purpose of this study is to investigate effects and range of generalization of stress expression behavior using Power Card strategy on interaction between a child with Asperger syndrome and his mother. In this study, thirteen-year child with Asperger syndrome underwent intervention for acquiring stress expression behavior using Power Card strategy. The intervention was conducted at the home of the subject with 5 to 7 minute-long sessions during two weeks. Data were taken and analyzed by using test scale, interview, recordings during the interaction between the subject and his mother at home. And On the basis of the research questions, this study were analyzed by classification of pre-intervention, during-intervention, and post-interven- tion, or by classification of pre-intervention and post-intervention. In this study, we found that Power Card strategy was effective on acquisition and generalization of stress expression behavior. The subject showed natural eye-contact in the interaction with the mother, increased in appropriate stress-expression behavior, was enhanced of duration of the interaction, and used various theme of the interaction. Also, the mother was declined of Parenting Stress and was enhanced of Parenting Self-Efficacy. Also, appropriate stress expression behavior were enhanced in the interaction in school, duration of the interaction was enhanced, theme of the interaction became variety, and attitudes of the peers on the subject were changed positively. Conclusively, the stress expression behavior intervention using Power Card strategy had positive effects on interactions between a child with Asperger syndrome and his mother

특수체육프로그램이 발달장애 학생의 문제행동 감소와 사회성에 미치는 영향

이재욱 부산외국어대학교 교육대학원 2016 국내석사

In the modern world, it is not easy for an individual to adjust to the ever changing society. Adjusting oneself to the society means the ability and the process of learning how to live with other people. The stormy period of adolescence is a phase that people undergo learning how to become a member of the society. However, since children during adolescence are both mentally and physically sensitive, many of them show behavior problems being unable to adjust to their school life or society. This study has two main purposes. The first one is to clarify whether implementing Special Physical Programs can reduce basic problematic behaviors of children with developmental disabilities. In order to investigate the reduction effects, preliminary inspections and post inspections have been conducted. The second purpose is to investigate the influence of Special Physical Programs on the sociality of children with developmental disabilities. Children with developmental disabilities generally lack sociality due to their problematic behavior. Therefore, this study examined the positive effects of Special Physical Programs on their sociality. Beforehand, the degree of the object’s problematic behaviors and sociality had been examined on the basis of the observation of three special education teachers, parent counselling, and the results of the K-CBCL test. The Special Physical Program had been implemented for 16times during 12weeks based on the basic curriculum of Physical Education at special schools. It became clear that Special Physical Programs at large reduce problematic behavior and have positive effects on sociality. In conclusion, it is necessary to develop diverse Special Physical Programs appropriate to children with development disabilities. What seems to be lacking in this study is sufficient time. The effects of Special Physical Programs are only limited in a the short term, therefore they should be implemented over a relatively long period.

성별에 따른 미각 역치의 차이

이재욱 대구가톨릭대학교 대학원 2014 국내석사

The aim of the study was to compare the gustatory function between men and age-matched women in Korean subjects. Subjects and Method Healthy non-smoking volunteers without smell and taste disorders were investigated. Thirty nine men and 39 age-matched women were evaluated for gustatory function. Whole mouth taste test was performed with successive solutions of sucrose, sodium chloride, citric acid, and quinine hydrochloride. The electrical taste thresholds were measured using an electrogustometer for the 4 different sites in the oral cavity, i.e., both sides of anterior and posterior tongue. Results Female subjects had lower mean values of detection and recognition thresholds for all the 4 tastes than male subjects, although these results did not reach statistical significance except for the detection threshold for salt and the recognition threshold for quinine. In electrogustometry, thresholds were significantly higher for men in the posterior tongue of glossopharyngeal nerve area than women. Conclusion Men had higher taste threshold than age-matched women. For additional information on the effects of gender and aging on taste thresholds, further studies including a large number of well-controlled subjects are essential.

A study on the relationship between perceived leadership styles and OCB with LMX as moderator

이재욱 신라대학교 2011 국내박사

개선된 유리강화 섬유를 활용한 기둥의 내진성능

이재욱 계명대학교 대학원 2010 국내석사

일반적인 구조물 보강재료인 탄소섬유는 유리섬유에 비해 높은 인장강도로 인해 보강재로써의 사용비중이 매우 높은 실정이지만 높은 가격 및 시공시의 단점으로 인해 그 사용 영역이 제한적이다. 이에 유리강화 섬유는 탄소섬유보다 높은 연성과 1/3정도의 가격 등 좋은 점이 있지만 인장강도가 탄소섬유대비 낮은 관계로 사용비중이 적다. 이에 본 연구는 기존 유리섬유의 인장응력범위를 벗어나 탄소섬유의 인장강도에 근접한 향상된 유리섬유 소재인 개선된 유리섬유가 개발 되어 이를 활용한 기둥의 보강 효과를 입증하고자 논문을 구성하게 되었다. 설계강도 65MPa의 고강도 RC 원형기둥을 제작하여 중심축 및 편심축(e=25mm)재하에 따른 거동양상 확인 및 횡보강 철근 (띠철근, 나선철근), 섬유보강(개선된 유리섬유, 탄소섬유시트)에 따른 강도증진효과 검증과 그에 따른 보강섬유의 거동을 확인하기위한 압축강도실험을 실시하였다. 그에 따른 결론으로 개선된 유리섬유보강 시험체의 탄소섬유시트 보강대비 약 10%내력증진을 보여 내진성능 내력증진에 효과가 있는 것으로 사료된다. 개선된 유리섬유보강 섬유로 구속된 시험체가 편심하중 재하 시 섬유 무보강 시험체 대비 최대 46%내력증가 및 18.95mm의 변위증가를 보여 탄소섬유시트섬유보강보다 개선된 유리강화섬유를 활용함이 내력증진 및 연성측면에서 뛰어나 내진성능 개선에 효과적일 것이라 사료된다. 편심 재하 시 섬유보강에 대한 내력증진이 중심 재하 일 경우보다 탄소섬유시트보강에서 최대 27%상향되어 편심축 하중을 받는 구조물 거동에 따른 섬유보강의 효과가 입증되었다. 편심축 재하 시험체는 무보강 띠철근 시험체에서 중심축 재하 시험체 대비 최대 39%의 내력 감소를 보여 편심하중을 받는 기둥의 거동이 중심축하중을 받는 기둥의 거동 보다 상대적으로 불리하여 실제 지진 발생에 대비한 기둥의 보강에 대한 더욱 많은 연구가 필요하다고 사료된다. 나선철근보강 시험체 대비 띠철근 보강 시험체의 보강섬유에 대한 구속효과가 최대 8%향상됨을 확인하였다. 나선철근 횡보강 시험체가 띠철근 횡보강 시험체 대비 10%의 내력증진을 확인하였고 전체적으로 변위도 증가하여 횡구속 철근 형상에 따른 내진성능의 차이를 확인 하였다. 각 위치별로 측정된 섬유보강 기둥의 평균 섬유변형률간의 표준편차가 매우 크게 나타나 섬유 보강된 시험체의 보강섬유의 파열이 국부적으로 나타남을 확인하였다. A carbon fiber reinforcement polymer of general structure is highly used as reinforcement due to its higher tensile strength as compared with glass fiber; however, it limits the range of usage owing to high price and weak points in construction. A glass fiber, by contrast, has higher ductility than a carbon fiber and a third price of a carbon fiber, but it is not widely used due to lower tensile strength as compared with a carbon fiber. So this study is carried out to verify the reinforcing effect of a column using high-strength glass fiber which exceeds tensile stress of existing glass fiber and approaches that of carbon fiber. After making high-strength RC circular column with 65MPa design strength, compressive strength test is implemented to identify the behavior according to the load of central axis and eccentric axis (e=25mm), and to verify the effect of strength improvement and the behavior of reinforcing fiber according to transverse reinforcement reinforcing bar (hoop bar, spiral bar) and fiber reinforcement (improved GFRP, Carbon Mat). From the results, it is verified that improved GFRP reinforcement has about 10% improvement in internal force as compared with Carbon Mat reinforcement. Under eccentric load, specimen confined with improved GFRP reinforcement has maximum 46% of internal force improvement and shows 18.95mm of displacement increase as compared with specimen without fiber reinforcement. Carbon Mat reinforcement increase internal force up to 27% under eccentric load as compared with fiber reinforcement under central load. In the hoop bar specimen without reinforcement, specimen under eccentric axial load shows internal force decrease up to 39% as compared with specimen under central axial load. The confinement effect of reinforcing fiber in hoop bar reinforcement specimen increases up to 8% as compared with spiral bar reinforcement specimen. Transverse reinforcement specimen with spiral bar has 10% internal force improvement and increases displacement overall as compared to transverse reinforcement specimen with hoop bar. The standard deviation among the average of fiber strain rates in fiber reinforcement column measured in each position shows high so that partial rupture in reinforcing fiber occurs.

구강 편평세포암종의 경부 림프절 전이에 대한 임상통계학적 연구

이재욱 경북대학교 대학원 2008 국내석사

We investigated a clinico-statistical evaluation on cervical lymph node metastasis of 183 patients who were diagnosed as oral squamous cell carcinoma in the department of Oral and Maxillofacial Surgery of Kyungpook National University Hospital from the 1st of January, 1999 to the 31th of December, 2007, and the following results were obtained. 1. Among 183 patients who have oral squamous cell carcinoma, 149 were male and 49 were female, which made the ratio of male to female 2.73 : 1. The average age of oral squamous cell carcinoma patients was 61.8, oral squamous cell carcinoma occurred the most between 70-79 years of age. 2. In the site distribution, lower alveolus and gingiva were the greatest with 56 cases, followed by tongue 43 cases, upper alveolus and gingiva 23 cases, mouth floor 21 cases. Maxillary sinus and mouth floor has higher tendency to cervical lymph node metastasis than other site. 3. The common chief complaints were pain, mass and swelling, ulcer, papillary and granular lesion. The cervical lymph node metastasis rate was higher in ulcer, mass and swelling and lower in papillary and granular lesion. 4. Higher T classification has higher tendency to cervical lymph node metastasis than more lower T classification. 5. Lesser differentiated tumor has higher tendency to cervical lymph node metastasis than more differentiated tumor. 6. Sensitivity, specificity on PET/CT was 87.5%, 58.3%. PET/CT has higher sensitivity and lower pseudo-negative value than CT, USG. 7. 5-year survival rate of the entire oral squamous cell carcinoma patients appeared to be 63.2%. In N classification, patients with N0 had the higher survival rate than patients with N1 and N2. 5-year survival rate according to modality of neck dissection was no neck dissection group, MRND group, SND group, RND group in decreasing order.

Gbps 급 Clock and Data Recovery Circuit에 관한 연구

이재욱 연세대학교 대학원 2001 국내석사

본 논문에서는 GHz 대역의 고속 클럭 신호를 필요로 하는 데이터 통신 시스템 분야에 응용될 수 있는 새로운 구조의 클럭 및 데이터 복원회로를 제안하였다. 제안된 회로는 고속의 데이터 전송시 주로 사용되는 NRZ 형태의 데이터 복원에 더욱 적합한 구조로서 NRZ 데이터가 주입될 경우에 위상동기 회로에 발생하는 주요 잡음원인인 high frequ ency jitter를 방지하기 위한 새로운 위상 검출구조를 갖추고 있어서 보다 안정적인 클럭을 제공할 수 있다. 또, 가변적인 지연시간을 갖는 delay cell을 이용한 PD를 제안하여 위상 검출기가 갖는 dead zone 문제를 없애고, 항상 최적의 동작을 수행할 수 있게 되어 빠른 locking time을 갖도록 하였다. 본 연구에서는 Gbps급 대용량의 데이터를 복원하기 위한 클럭 생성을 목표로 하여 CMOS 0.25㎛공정을 사용하여 설계한 후 그 동작을 data와 clock의 phase error에 따른 post-layout simulation을 통해 검증하였다. 이 회로는 두 개의 루프를 갖는 hybrid 형태로 외부의 제어신호에 의해 각 루프를 선택적으로 동작하게 하여 데이터 전송이 중단되었을 경우에도 안정적인 시스템 클럭을 발생할 수 있도록 하였다. GHz 대역의 높은 주파수에서의 동작을 보장하기 위해 PD 및 MUX, 전하펌프 등 각 기능동작 블록을 fully differential logic으로 설계하여 1.4 Gbps에서 1.7 Gbps까지의 데이터를 수신하여 복원할 수 있게 하였다. 또, 이 시스템은 Gigabit Ethernet Protocol에 맞추어 설계되어 high speed switch 및 data transceiver 등 주요 데이터 통신 시스템에 널리 이용될 수 있을 것이다. In this thesis, a new clock and data recovery circuit is proposed for the applications of data communication system requiring GHz-range clock signal. The circuit is suitable for recovering NRZ data which is widely used to high frequency data transmission in GHz ranges. The high frequency jitter is one of major noise factors in PLL, particularly when NRZ data patterns are used. A novel phase detector in the proposed circuit is able to suppress this noise, therefore stable clock generation is easily achieved. Furthermore, this phase detector has an adaptive delay cell removing the dead zone problem and having the fittest characteristic, thu s the circuit can obtain fast locking mode. The proposed circuits are designed based on CMOS 0.25㎛ fabrication process and verified by HSPICE p ost-layout simulation. This circuits assume the form of hybrid loops which are selected by control signal. Due to this configuration, the clock generation can be stabilized even if the data transmission is interrupted.