Pertuzumab, trastuzumab, docetaxel을 투약한 진행성 HER2 양성 유방암 환자에서 HER2/CEP17 비율과 생존 성적의 연관성 분석

학위논문(석사) -- 서울대학교대학원 : 의과대학 의학과, 2023. 2. 김동완.Background: HER2 positivity is a well-known predictive biomarker for HER2 targeted therapy. However, the duration of response to HER2-targeting agents varies from patient to patient. This study investigated the association between HER2/CEP17 ratio and treatment outcome in patients with advanced HER2-positive breast cancer. Methods: This is a single center retrospective study. Patients with advanced HER2-positive breast cancer treated with first-line pertuzumab, trastuzumab, and docetaxel were included. The association between HER2/CEP17 ratio and treatment outcome was assessed. Results: A total of 165 patients were included in this study with a median follow-up duration of 29.0 months. The correlation between HER2/CEP17 ratio and treatment outcome was assessed in 88 patients. Thirty-five patients had archival HER2 ISH result. Additional ISH test was performed in 53 patients with IHC 3+ who did not have previous ISH results. Cox proportional hazard analysis revealed that HER2/CEP17 ratio is correlated with PFS (HR 0.23, p < 0.001). When dichotomized by the median HER2/CEP17 ratio, patients with higher HER2/CEP17 ratio had significantly longer PFS (median PFS, 37.5 vs. 17.4 months, HR 0.40, p = 0.003) and numerically higher ORR (54.5% vs. 34.1%, p = 0.085). Multivariate analysis revealed that HER2/CEP17 ratio is an independent prognostic factor for PFS (HR 0.72, p = 0.001). HER2/CEP17 ratio was associated with PFS in both HER2 IHC 1+/2+ patients (HR 0.12, p = 0.037) and IHC 3+ patients (HR 0.18, p = 0.001). Conclusion: This is one of the first studies to report that higher HER2/CEP17 ratio is associated with longer PFS in HER2-positive advanced breast cancer patients treated with dual HER2 blockade. In addition, this study identified the prognostic role of ISH even in patients with HER2 IHC 3+. It would be helpful to perform ISH in patients with HER2 IHC 3+ to make better prediction of treatment outcome.배경: HER2 양성 여부는 HER2 표적치료제의 효과에 대한 예측 인자로 잘 알려져 있다. 하지만 HER2 표적치료제에 대한 치료 반응이 유지되는 기간은 환자마다 다르다. 본 연구는 진행성 HER2 양성 유방암에서 HER2/CEP17 비율과 치료 성적과의 연관성에 대해 탐구하였다. 방법: 진행성 HER2 양성 유방암의 일차 치료로 pertuzumab, trastuzumab, docetaxel을 투약한 환자들을 분석한 단기관 후향적 연구이다. HER2/CEP17 비율과 치료성적의 관련성을 평가하였다. 결과: 총 165명의 환자가 등록되었고 중앙 추적관찰 기간 29.0개월 동안 관찰하였다. HER2/CEP17 비율과 치료성적 간의 관계는 총 88명에서 평가되었다. 35명에서는 HER2 ISH 결과가 존재하였고, 이전에 ISH를 시행하지 않은 IHC 3+ 환자 중 53명을 대상으로 ISH 검사를 추가 시행하였다. Cox 비례위험모형 분석 결과 HER2/CEP17 비율은 무진행 생존기간과 유의미한 연관성을 보였다 (위험비 0.23, 95% 신뢰구간 0.11-0.49). HER2/CEP17 비율의 중앙값으로 양분하여 분석하자, HER2/CEP17 비율이 더 높은 군에서 무진행 생존기간이 유의미하게 증가하였으며 (중앙 무진행 생존기간, 37.5 vs 17.4개월, p = 0.003), 객관적 반응률이 수치 상 높았다 (54.5% vs 34.1%, p = 0.085). 다변량분석 결과 HER2/CEP17 비율은 무진행 생존기간에 대한 독립적 예후인자였다 (위험비 0.72, p = 0.001). HER2/CEP17 비율은 HER2 IHC 1+/2+인 환자군과 3+인 환자군 모두에서 무진행 생존기간과 유의미한 연관성을 보였다 (각각 위험비 0.12, p = 0.037; 위험비 0.18, p = 0.001). 결론: 본 연구는 HER2 양성 진행성 유방암에서 HER2 표적치료제를 2종 사용할 때 HER2/CEP17 비율이 높으면 무진행 생존기간이 길다는 것을 보인 첫 연구들 중 하나이다. 아울러, HER2 IHC 3+인 환자에서도 ISH가 예후인자로 작용한다는 것을 보였다. HER2 표적치료의 성적을 더 잘 예측하기 위하여 HER2 IHC 3+ 환자에서도 ISH를 시행하는 것이 도움이 될 수 있음을 제안한다.List of Tables 1 List of Figures 2 Abbreviations 3 Chapter 1. Introduction 4 Chapter 2. Materials and Methods 7 2.1. Study design and population 7 2.2. Analysis of tumor subtype and HER2 ISH 9 2.3. Statistical analysis 11 Chapter 3. Results 13 3.1. Patient characteristics 13 3.2. Predictive implication of HER2 ISH 18 3.3. Predictive implication of HER2 ISH according to HER2 IHC 24 3.4. Predictive implication of HER2 ISH copy number 27 3.5. Analyses on other clinicopathologic factors 30 3.6. Multivariate analysis 35 Chapter 4. Discussion 37 Bibliography 40 Abstract in Korean 44석

무인 수중 글라이더의 설계 연구

A design study was performed on the torpedo-shaped underwater glider which can control the orientation using a weight shifter and buoyancy engine. An analysis on the structure of the glider was performed. The size of the glider was designed to have weight a little over the buoyancy and the shape of the hull was designed using Myring profile to reduce down the drag force. Also, the stress and strain analysis was performed. The interior parts of the glider including electronic components was designed. An analysis on the posture of the underwater glider was performed. In addition to this, the dynamics analysis in the underwater glider was performed with a numerical analysis.표 목차 그림 목차 Abstract 1. 서 론 1.1 연구배경 1.2 연구목적 2. 무인 수중 글라이더의 설계 2.1 무인 수중 글라이더의 구성 및 개념설계 2.2 무인 수중 글라이더의 형상 설계 2.2.1 선수부 설계 2.2.2 중앙부 설계 2.2.3 선미부 설계 2.2.4 내부 설계 3. 무인 수중 글라이더의 동체 내압 해석 3.1 동체의 좌굴 해석 모델 3.2 해석 조건 및 경계조건 3.3 동체의 내압 해석결과 4. 무인 수중 글라이더의 자세 해석 5. 무인 수중 글라이더의 동역학 모델링 및 시뮬레이션 5.1 시스템 구성 및 수학적 모델링 5.2 시뮬레이션 및 해석 6. 결론 참고문

An Empirical Study on the Effect of New Business Development Strategy and Total Marketing Capacity on Performance : Primarily on the Shipping Industry in Korea

Nowadays, New business development in the company becomes more significant activity not only to maintain company's revenue but also to achieve the future vision on the basis of enterprise. The purpose of this study was to explore the effects of new business development strategy and total marketing capacity on corporate performance primarily on the shipping industry in Korea. The study also investigates the moderating effects of management control system and performance evaluation system to the total marketing capacity and performance. An empirical study was carried out to examine the effects of new business development strategy and total marketing capacity on corporate performance on the shipping industry in Korea. The research model is consists of 5 factors(1) Concentration strategy (2) diversification strategy (3) integration strategy. It was found out that concentration strategy has the best performance and diversification strategy has better results than integration strategy does. But, From the perspective of non-financial performance, there were no differences on among these 3 types of new business development strategy. 2) From the perspective of different categories of new business development strategy there are no differences in the level of marketing capacity. However, there are average differences in management assets, marketing culture, planning capability and implement capability. 3) Total marketing capacity representing sustained competitive advantage and business level strategy has positive effects to the performance resulting from new business development strategy. 4) Most of Korean shipping companies used all kinds of control method such as action control and result control in the management control system. 5) The hypothesis that performance evaluation system is different based on total marketing capacity was supported. 6) It was found out that there were no significant relationships between Management control system and new business development performance. 7) There are differences in new business development strategy, Total marketing capacity and Management control system in the same industry. consequently, the specific differences in the level of performing and establishing new business development strategy should be considered. As a result, The new business development is a main factor to enhance the competitiveness of the company. Therefore, Systematic and strategic approach to the new business development should be applied. For the practical viewpoint of this study, the effects of total marketing capacity to the performance and SCA(sustainable competitive advantage) should be analyzed. This study helps the shipping company to design an appropriate management control system for the levels marketing capacity and plan to make performance evaluation system or indexes.1) ocean-going shipping service 2) Freight forwarding service 3) shipping agent service in Korea by the use of questionnaire method. The factor analysis, multiple regression analysis, t-test analysis and two-way ANOVA(Analysis of Variance) were used to analyze the data. The results of the analysis led to the following conclusions : 1) From the perspective of financial performance, There are significant differences in financial performance among the types of new business development strategynew business development strategy, total marketing capacity, management control system, performance evaluation system and corporate performance. Consequently, 8 hypothesis were formulated and tested to find out interrelationship of these 5 factors. The Data investigating the effects of new business development strategy and total marketing capacity on corporate performance were collected from 250 shipping companies handling 3 different types of shipping service productAbstract Ⅰ 제 1 장 서 론 1 제 1 절 연구의 배경 및 필요성 1 제 2 절 연구의 목적 3 제 3 절 연구의 대상과 범위 4 제 4 절 연구의 방법과 구성체계 4 1. 연구방법 4 2. 연구의 구성체계 5 제 2 장 이론적 고찰 6 제 1 절 신규사업 개발전략 6 1. 신규사업의 개념 6 2. 신규사업 개발전략 18 3. 신규사업 개발전략 유형 32 제 2 절 종합 마케팅능력 37 1. 지속적 경쟁우위 37 2. 핵심자원과 역량 44 3. 마케팅능력 47 제 3 절 경영(관리)통제 유형 54 1. 통제의 개념 54 2. 경영통제시스템 58 3. 전략적 통제유형 60 제 4 절 성과평가 유형과 신규사업 성과 64 1. 성과평가 시스템 64 2. 성과평가의 유형 67 3. 신규사업 성과파악을 위한 균형성과표 70 제 3 장 연구모형 및 가설 설정 74 제 1 절 연구모형의 설계 74 제 2 절 연구 가설의 설정 76 1. 신규사업 개발전략과 개발성과간의 관계에 대한 가설 76 2. 신규사업 개발전략과 종합 마케팅능력간의 관계에 대한 가설 77 3. 종합 마케팅능력과 신규사업 개발성과간의 관계에 대한 가설 78 4. 관리통제 유형과 종합 마케팅능력의 관계에 대한 가설 79 5. 성과평가 유형과 종합 마케팅능력의 관계에 대한 가설 80 6. 관리통제 유형과 신규사업 개발성과간의 관계에 대한 가설 80 7. 성과평가 유형과 신규사업 개발성과간의 관계에 대한 가설 81 8. 업종별 특성차이에 대한 가설 82 제 3 절 변수의 조작적 정의 및 측정 83 1. 신규사업 개발전략 83 2. 종합 마케팅능력 84 3. 관리통제 유형 및 성과평가 유형 88 4. 신규사업 개발성과 89 제 4 장 실증분석 92 제 1 절 조사 설계 92 1. 연구대상 및 표본추출 92 2. 자료수집 방법 94 제 2 절 표본의 일반적 특성 95 1. 표본의 특성 95 2. 신뢰성 및 타당성 분석 100 제 3 절 가설의 검정 106 1. 신규사업 개발전략과 개발성과간의 관계에 대한 가설 검정 106 2. 신규사업 개발전략과 종합 마케팅능력간의 관계에 대한 가설검정 107 3. 종합 마케팅능력과 신규사업 개발성과간의 관계에 대한 가설검정 108 4. 관리통제 유형과 종합 마케팅능력의 관계에 대한 가설검정 112 5. 성과평가 유형과 종합 마케팅능력의 관계에 대한 가설검정 114 6. 관리통제 유형과 신규사업 개발성과간의 관계에 대한 가설검정 115 7. 성과평가 유형과 신규사업 개발성과간의 관계에 대한 가설검정 119 8. 업종별 특성차이에 대한 가설검정 122 9. 가설검정결과의 요약 129 제 5 장 결 론 133 제 1 절 연구결과의 요약 133 제 2 절 연구결과의 시사점 135 제 3 절 연구의 한계 및 향후 연구방향 136 참고문헌 138 국내 문헌 138 외국 문헌 140 부 록〔 설 문 지 〕 14

A Design and Implementation of Multistage Database for Integrated Information Management on Shipboard

Ships are equipped with several kinds of navigation equipments which generate huge amount of data. Although these data have been mainly used for the safe navigation of ships, their usability can be enhanced if they are managed on a database. Because these data have different formats according to the kinds of equipments, however, an integrated database is required. This thesis presents a design and implementation of such database. International Electro-technical Commission(IEC) is preparing the standard, IEC 61162-450, which specifies data exchange between shipboard equipments. This thesis adopts the standard as the basis of integrated information management. Data in the form of sentences specified in the standard, NMEA 0183 ver. 4.0, are collected from the shipboard networks, and then transformed and saved in a database. The database, in turn, can provide several information services to applications. However, the database may become full soon, because huge amount of data are saved continuously. To cope with this problem, this thesis proposes a multistage database methodology which can always keep the database under full by means of sampling mechanism. The data of the database are sampled, and then saved in another database, called second stage database. To prevent overflow of the database, some old data which already sampled can be deleted from the database. By this way, shipboard data are stably collected and managed, and then applied to the safe and efficient navigation of ships. To verify the functionality of the methodology, a prototype system has been implemented and tested. It is expected to become a component of e-Navigation implementation in the future.제 1 장 서 론 1 제 2 장 관련 연구 3 2.1 MiTS(Maritime information Technology Standard) 3 2.2 NMEA 0183 센텐스 4 2.2.1 센텐스의 구조 5 2.2.2 센텐스의 종류 5 제 3 장 다단 데이터베이스 서버 설계 9 3.1 다단 데이터베이스의 설계 10 3.1.1 1차 데이터베이스 10 3.1.2 2차 데이터베이스 13 3.2 데이터베이스 모듈의 설계 15 3.2.1 데이터 저장 모듈 15 3.2.2 데이터 샘플링 모듈 17 3.2.3 데이터 삭제 모듈 25 3.2.4 데이터 검색 모듈 29 제 4 장 구현 및 시험 32 4.1 데이터베이스의 구현 32 4.2 데이터베이스 모듈의 구현 및 시험 34 4.2.1 데이터 저장 모듈 34 4.2.2 데이터 샘플링 모듈 35 4.2.3 데이터 삭제 모듈 37 4.2.4 데이터 검색 모듈 40 제 5 장 결론 및 향후 과제 46 참고 문헌 4

캐릭터 콜라보레이션에서 소비자와 캐릭터간의 이미지 일치성이 화장품 제품평가에 미치는 영향: 이상적인 이미지 일치성과 실제 이미지 일치성의 상대적 중요도 중심으로

학위논문 (석사)-- 서울대학교 대학원 : 경영학과, 2017. 2. 김상훈.An increasing number of companies develop strategic marketing collaborations with other businesses to reach new consumers. One popular collaboration method is character collaborationhowever, little research has examined the effects of character collaboration, specializing in the collaborated characters image and its congruence with a consumers image in the cosmetics industry. This research hypothesizes that consumers who perceive the collaborated characters image as being congruent with their ideal self-images have a more positive evaluation of collaboration products, compared to perceiving it as being congruent with their actual self-images. The present research proposes that the fundamental psychological motive to improve ones self to achieve an ideal image is the key to influencing consumers to view the collaboration products more favorably. This phenomenon is observed, in particular when consumers perceive the cosmetic products as publicly consumed products. The findings of the study show that consumers evaluate the collaboration products more favorably when they perceive ideal self-images from the characters and believe that the cosmetic products as publicly consumed products because they have a stronger self-improvement motive. This research concludes consumers with perceptions of the cosmetic products as public consumption products have a more positive evaluation of the collaboration products as they are motivated to have their self-images as close as possible to their ideal self-image. The implications and limitations of the findings are discussed.1. INTRODUCTION 1 2. THEORETICAL BACKGROUND 3 2.1. Collaboration 3 2.2. The Self-Congruence Theory 3 2.3. The Match-up Hypothesis 5 2.4. Self-Improvement Motive 6 2.5. Perception of Product Usage Situation 7 3. EXPERIMENT 8 3.1. Method 9 3.2. Results 10 4. DISCUSSION 15 5. CONCLUSION 18 5.1. Academic Contribution 18 5.2. Practical Implication 19 5.3. Limitations and Future Research 20 REFERENCES 21 APPENDIX 25 ABSTRACT (KOREAN) 36Maste

폐쇄성 수면 무호흡에 대한 새로운 접근법으로써의 이식형 전자 장치 개발

학위논문(박사)--서울대학교 대학원 :공과대학 전기·정보공학부,2019. 8. 김성준.Obstructive sleep apnea (OSA) is a disorder with high prevalence that 13 % of men and 6 % of women in North America suffer from. It is often regarded as a mere discomfort at night though, chronic OSA may involve sequelae such as insulin resistance, vascular diseases, and impaired quality of life due to excessive sleepiness. Although there are existing therapies such as continuous positive airway pressure (CPAP), oral appliances, and surgical operations, those therapies are not applicable to some patients due to low effectiveness, low adherence, or high invasiveness. Therefore, it is necessary to develop break-through therapies which can overcome the limitations of the conventional therapies. In this dissertation, two implantable electronic devices are suggested as novel approaches to treat OSA. They provide unique methods to retain patency of the retrolingual and the retropalatal region which are considered as main contributors to pharyngeal collapse. First, a magnetic cuff system was designed and fabricated for stimulating the hypoglossal nerve which the innervates the extrinsic tongue muscle, the genioglossus. The system consists of a magnet-embedded nerve cuff electrode and a stimulation pulse generator. The substrate material used for the electrode is a liquid crystal polymer (LCP), characterized by properties of biocompatible, flexible, and near-hermetic. The electrode can be easily installed on and removed from the nerve repeatedly, owing to magnetic forces of the embedded rare-earth magnets. To demonstrate feasibilities of the system in hypoglossal nerve stimulation, in vivo as well as in vitro evaluations were conducted. Electrochemical impedance spectroscopy (EIS) was measured in a PBS solution using a three-electrode cell to figure out magnitude and phase of the impedance in the frequency ranging 1 Hz ̶ 100 kHz. The electrode was further evaluated in vivo to stimulate the hypoglossal nerve of a rabbit. With the applied stimulation, protrusion of the tongue and the contraction of the genioglossus was observed with bare eyes and C-arm fluoroscopy respectively. A preliminary study was conducted to figure out the effect of the electrical stimulation on the retropalatal opening under a hypothesis that the electrical stimuli contracts the soft palate. Through the study, elevation of the soft palate was shown via a C-arm fluoroscopy with stimulation pulse parameters of 1.00 mA, 636 μs, and 100 Hz for an amplitude, duration, and frequency, respectively. Based on the finding, a palatal implant system was designed and fabricated. The system consists of two main parts, an intra-oral device that receives stimulation parameters via ZigBee from an external controller and an implant that receives power and data from the intra-oral device via an inductive link. The intra-oral device has a shape of a mouth-piece to easily get equipped in the mouth and the whole device is packaged by a silicone elastomer. The implant consists of multiple LCP sheets on which metals composing a coil, circuit, and electrode pattern are patterned. To evaluate wireless performance of the fabricated system, power-related terms such as a total power efficiency, supplied/received power, and received peak voltage were measured varying the distance between the transmitter and the receiver antenna coils. An averaged duty-cycle error of recovered PWM signals at the receiver was also calculated based on the measurement in the range of the distances to evaluate data telemetry of the wireless transmission. Further assessments were conducted in vitro to demonstrate feasibility of the stimulation electrodes in a metal-electrolyte interface using a PBS solution. Impedance, charge storage capacity, and charge injection capacity of the fabricated electrode were obtained and analyzed using an electrochemical impedance spectroscopy. After the evaluations, the system was applied to a rabbit and the soft palate stimulation was conducted in vivo. As expected, contraction of the soft palate was shown via a C-arm fluoroscopy when the electrical stimulation was applied. Finally, several discussions on the developed devices were addressed.수면 무호흡은 북미 남성의 13% 그리고 여성의 6%가 겪고 있을 정도로 유병률이 높은 질병이다. 단순히 밤에 불편한 것 정도로 생각될 수 있지만, 수면 무호흡은 인슐린 저항성, 심혈관 질환, 그리고 과도한 졸림으로 인한 삶의 질 저하와 같은 심각한 후유증을 유발할 수 있다. 양압기도법 (CPAP), 구강 장치, 외과적 수술과 같은 기존의 치료법들은 낮은 효과, 낮은 순응도, 또는 높은 침습성 때문에 일부 환자들에게는 적용이 불가능한 점이 있다. 따라서, 이러한 기존 치료법들의 한계점을 극복하기 위해서는 혁신적인 치료법을 개발할 필요가 있다. 본 학위 논문에서는 수면 무호흡을 치료하기 위한 새로운 접근법으로써 두개의 삽입형 전자 장치를 제안한다. 이 장치들은 인두 폐쇄의 주된 원인인 설 기저부 및 연구개 기저부의 개방성을 확보하기 위한 특별한 방법을 제공한다. 먼저, 혀의 외부 근육을 연결하는 설하 신경을 자극하기 위해 마그네틱 커프 시스템을 디자인하고 제작하였다. 이 시스템은 자석이 내장된 신경 커프 전극과 자극 펄스 생성기로 이루어져 있다. 전극에 사용된 기판 물질은 액정 폴리머인데 생체 호환적이며 유연하고 뛰어난 밀봉성을 특징으로 한다. 전극에 내장된 희토류 자석의 자기력 덕분에 전극을 신경에 쉽게 설치하거나 떼어낼 수 있다. 제작된 전극의 설하 신경 자극에의 실행 가능성을 검증하기 위해, 실험관 내 실험 및 생체 내 실험이 수행되었다. 1 Hz 에서 100 kHz에 이르는 주파수에서 임피던스의 크기와 위상을 알아내기 위해, PBS 용액에 설치된 삼전극 시스템에서 전기화학적 임피던스 스펙트럼을 측정하였다. 또한, 토끼의 설하신경을 자극하기 위해 생체 내 실험이 수행되었다. 자극이 인가되는 동안, 이설근의 수축을 C-arm fluoroscopy 장치를 통해 확인할 수 있었으며 및 맨 눈으로도 혀의 돌출을 확인할 수 있었다. 전기 자극이 연구개 수축을 유발한다는 가정 하에서, 전기 자극이 연구개 기저부 개방성에 미치는 효과를 알아보기 위해 사전 실험이 수행되었다. 이 실험을 통하여, 1.10 mA의 진폭, 636.3 μs의 지속 시간, 100 Hz의 주파수를 가진 전류 자극이 연구개의 위치를 상승시킨다는 것을 C-arm fluoroscopy를 통하여 확인할 수 있었다. 위의 발견을 기반으로 하여, 구개 임플란트 시스템이 디자인되고 제작되었다. 이 시스템은 외부 컨트롤러로부터 지그비 통신을 통해 자극 파라미터를 수신하는 구강 내 장치와 유도 결합을 통해 구강 내 장치로부터 파워와 데이터를 수신하는 임플란트로 구성되어 있다. 시스템의 퍼포먼스를 평가하기 위해서, 송신 및 수신 안테나 코일 사이의 거리를 변화시키면서 총 파워 효율, 공급/수신 파워와 같은 파워와 관련된 항들이 측정하였다. 또한, 그 거리 범위에서 수신단에서 복구한 PWM 신호의 평균 duty-cycle 에러를 측정된 값을 기반으로 계산하였다. PBS 용액을 이용한 금속-전해질 계면에서 자극 전극으로써의 사용 가능성을 확인하기 위해서 시험관 내 검증이 추가적으로 수행되었다. 전기화학 임피던스 스펙트럼을 통해 전극의 임피던스, 전하 저장 용량, 그리고 전하 주입 용량을 구하고 분석하였다. 시험관 내 검증이 끝난 후에, 토끼의 연구개 자극을 위하여 생체 내 실험이 진행되었다. 예상했던 대로, 전기 자극이 인가되었을 때, 연구개 자극이 수축되는 것을 C-arm fluoroscopy를 통하여 확인할 수 있었다. 마지막으로, 개발된 장치들에 대한 몇몇의 discussion이 다루어졌다.List of Figures List of Tables List of Abbreviations Chapter 1. Introduction ············································ 1 1.1 . Obstructive Sleep Apnea (OSA) ······························· 2 1.1.1. Pathogenesis of OSA ······································· 2 1.1.2. Conventional Therapies ···································· 3 1.1.2.1. Continuous Positive Airway Pressure ··········· 4 1.1.2.2. Therapies of Tongue-related OSA ··············· 4 1.1.2.3. Therapies of Palate-related OSA ················ 5 1.2. Electrical Stimulation for OSA treatment ····················· 6 1.2.1. Neural and Neuromuscular Stimulation ···················· 7 1.2.2. Hypoglossal Nerve Stimulation (HNS) ···················· 8 1.2.3. Soft Palate Stimulation (SPS) ······························ 9 1.3. Suggested Approaches ········································· 10 1.3.1. Liquid Crystal Polymer (LCP)···························· 10 1.3.2. Magnetic Cuff System for HNS ·························· 12 1.3.3. Palatal Implant System for SPS ·························· 15 1.4. Objectives of this Dissertation ································ 17 Chapter 2. Methods ················································ 18 2.1. Magnetic Cuff System for HNS ······························ 19 2.1.1. Overview ················································ 19 2.1.2. Magnet-Embedded Nerve Cuff Electrode ················ 19 2.1.2.1. Electrode Design ······························ 19 2.1.2.2. Fabrication ···································· 19 2.1.3. External Pulse Generator ································· 23 2.1.3.1. Circuit Description ···························· 23 2.1.3.2. Fabrication ···································· 24 2.1.4. Evaluations ·············································· 24 2.1.4.1. Electrochemical Measurements In Vitro ······· 23 2.1.4.2. Animal Testing In Vivo ························ 25 2.2. Palatal Implant System for SPS ······························ 27 2.2.1. Pilot Study In Vivo ······································· 27 2.2.2. Overview ················································ 30 2.2.3. Palatal Implant ··········································· 31 2.2.3.1. Circuit Description ······························ 31 2.2.3.2. Fabrication ······································ 34 2.2.3.2.1. Electrode Layers ···················· 34 2.2.3.2.2. Antenna Coil and Circuit Layers ···· 35 2.2.3.2.3. Multi-layer Lamination ············· 36 2.2.3.2.4. Post-lamination Process ············· 39 2.2.4. Intra-Oral Device ········································ 40 2.2.4.1. Circuit Description ···························· 40 2.2.4.1.1. ZigBee Receiver ···················· 40 2.2.4.1.2. Class-E Amplifier ··················· 42 2.2.4.1.3. ASK Modulation ···················· 45 2.2.4.1.4. Power Management ················· 45 2.2.4.2. Fabrication ···································· 46 2.2.5. Inductive Link ··········································· 47 2.2.5.1. Design of Coil Antennas ······················· 48 2.2.5.2. FEM Simulation ······························· 50 2.2.5.3. SPICE Simulation ····························· 52 2.2.6. Evaluations ·············································· 53 2.2.6.1. Wireless Power Transmission ················· 53 2.2.6.2. Wireless Data Transmission ··················· 54 2.2.6.3. Electrochemical Measurements In Vitro ······· 55 2.2.6.4. Animal Testing In Vivo ························· 56 Chapter 3. Results ·················································· 58 3.1. Magnetic Cuff System for HNS ······························· 59 3.1.1. Fabricated System ········································ 60 3.1.2. Electrochemical Measurements In Vitro ·················· 61 3.1.3. Animal Testing In Vivo ··································· 62 3.2. Palatal Implant System for SPS ······························· 63 3.2.1. Pilot Study In Vivo ······································· 63 3.2.2. Fabricated System ········································ 65 3.2.3. Wireless Power Transmission ···························· 68 3.2.4. Wireless Data Transmission ······························ 71 3.2.5. Electrochemical Measurements In Vitro ·················· 72 3.2.6. Animal Testing In Vivo ··································· 77 Chapter 4. Discussions ············································· 79 4.1. Magnetic Cuff System for HNS ······························· 80 4.1.1. Cuff-to-Nerve Diameter Ratio ···························· 80 4.1.2. Magnetic Forces ········································· 82 4.1.3. Stimulation Parameters ··································· 83 4.1.4. Weight and Size ·········································· 84 4.1.5. Cost Effectiveness ······································· 85 4.1.6. Extension to Multi-channels ······························ 85 4.2. Palatal Implant System for SPS ······························· 86 4.2.1. Reliability of Intra-Oral Device ·························· 86 4.2.2. Palatoglossus Coupling ·································· 88 4.2.3. Potential Developments ·································· 89 4.2.3.1. Monolithic Packaging of Implant ···············89 4.2.3.2. Integration of Sensors ·························· 90 4.2.3.3. Application of Mandibular Advancement ······ 91 4.2.3.4. Improved ASIC Design for Palatal Implant ···· 92 4.2.3.4.1. Circuit Design ······················ 93 4.2.3.4.2. Digital Protocol ····················· 94 4.2.3.4.3. Circuit Implementation ············· 96 Chapter 5. Conclusion ············································ 98 References ·························································· 103 국문 초록 ························································· 109Docto

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