간암에서 SYK의 프로모터 CpG island 과메틸화에 의한 발현소실 및 종양억제자로서의 역할에 대한 연구

학위논문 (박사)-- 서울대학교 대학원 : 협동과정 종양생물학전공, 2014. 2. 강경훈.The spleen tyrosine kinase (SYK) has predominantly been studied in hematopoietic cells in which it is involved in immunoreceptor-mediated signaling. However, SYK expression is evidenced in numerous nonhematopoietic cells and its down-regulation has been shown to be involved in tumor formation and progression. Our team has reported that SYK promoter methylation identifies a subset of hepatocellular carcinoma (HCC) with poor prognosis but little is known regarding a biological role of SYK in HCC. We found that SYK promoter methylation is a common event in HCC and is closely associated with its expression. We established stable HCC cell lines that contain SYK gene in inducible expression vector and then compared RNA expression profiles of HCC cell lines with or without induction of SYK. Gene ontology analysis revealed that the SYK-regulated genes are enriched among genes involved in cell adhesion and cell growth. Indeed, we found that SYK increased cell adhesion to fibronectin and decreased cell proliferation. Induced expression of SYK decreased cell migration and invasion by coordination with adhesion molecules as well as suppression of Rho-family GTPases. Our findings suggest that SYK loss is implicated in cell proliferation, migration, and invasion of HCC cells.Abstract Contents List of Tables List of Figures Introduction Material and Methods Cell lines and 5-Aza-dC treatment Tet-on inducible expression system GFP tagged SYK expression vector and transfection Expression microarray Sodium bisulfite modification and methylation analysis RT-PCR Western blot Colony formation assay Cell proliferation assay Cell migration and invasion assay Immunofluorescence Cell adhesion assay Coimmunoprecipitation Statistical Analysis Results Correlation of SYK expression with methylation status Gene expression profiling Gene ontology analysis of SYK-dependent genes in HCC cells Expression of SYK suppresses cell growth Effect of SYK on cell adhesion, migration and invasion Cellular redistribution of SYK following adhesion to fibronectin SYK associates with cytoskeleton and adhesion molecules Expression of SYK cause a suppression of Rho-Family GTPases and stress fiber formation Discussion References Abstract in KoreanDocto

보험회사의 손해사정 프로세스 혁신 후 정수계획법과 시뮬레이션을 활용한 인건비 최소화

MasterThis study presents innovating process and minimizing staff expense of an insurance company’s claim using integer programming and simulation. Since the insurance’s loss rate has increased and profitability has decreased, the insurance companies need to make operation more deployable and efficient and build effective staffing plan to keep the margin by minimizing expense. For more efficient claim processes, process innovation was executed by adding new sub-processes or omitting redundant or unnecessary sub-processes which cause time-consuming issues. And, the proper staff number for each sub-process of an insurance company’s innovated claim processes was calculated to minimize expense. For that, a mathematical model using integer programming was built and simulation was executed. Like widely used, the integer programming can draw the optimal staff number to minimize the expense and simulation with Arena can consider queuing of policyholders in every sub-processes. Integer programming formulation and simulation details are described in ‘Method’ section. Finally, the minimized expense was calculated. Time lengths of each sub-processes and number of cases handled by each sub-processes were measured by questioning to staff. Then, the claim processes innovation which can solve present problems like frequent loss of received documents from policyholders or too much irrelevant task of claim staff was executed by omitting current sub-processes or adding new sub-processes. With the innovated process, allocation of proper person to proper position was executed for higher efficiency and lower expense. For example, scanning received documents or key-in information which have been handled by claim staff were allocated to ‘Receiving Staff’ who don’t need high level of claim knowledge and don’t need to pay high salary. Then, the optimal number of staff was calculated with integer programming. However, since there is still problem related to policyholders’ waiting time, it was simulated by minimizing policyholder’s waiting time. Finally the reasonable staff number was calculated. As a result, in the innovated processes, two sub-processes were distributed into different supervising staff from ‘Claim Staff’ into ‘Professional Counseling Staff’ and ‘Receiving Staff’ and the total process number was changed from fourteen to fifteen. In addition to that, 86 staff can be diminished from 1,293 into 1,207 and staff expense was decreased from 4,121,200,000 KRW into 3,044,000,000 KRW.보험 산업 내의 치열해진 경쟁에 대응하기 위해 보험 회사들이 최근 출시한 보험 상품들은 대체로 기존 상품에 비해 보장 범위가 넓어지면서 손해 사정 업무는 지속적으로 증가하게 하였지만 수입 성장률은 둔화하게 하여 왔다. 또한 보험 산업의 손해율이 증가하고 신규 상품의 성공을 통한 수익 창출 여력이 줄어들면서, 보험 회사의 임직원들은 내부 운영의 효율성을 증대시킴으로써 비용을 감소시켜야 할 방법을 찾아야 할 도전에 직면하게 되었다. 이에, 국내 G 보험 회사는 접수된 서류의 분실로 인해 처리 시간과 고객 불만 증가나 상대적으로 고임금인 손해사정 업무 담당자들이 고객 불만 전화 응대, 정보 입력과 같이 단순한 업무에 지나치게 많은 시간을 소비하는 것과 같이 반복되는 고질적인 이슈들을 해결하도록 중복되는 프로세스들을 제거하고 효율을 위해 필요한 프로세스들을 추가하는 작업을 통해 손해 사정 프로세스를 혁신하였다. 그리고 역량과 인건비를 기준으로 업무 난이도에 걸맞게 인력을 재배치하여 인건비는 낮추고 속도, 정확성이라는 효율은 높이도록 하였다. 이후 이 논문을 통해 수리 모델링을 적용하여 보다 정확하고 정교한 인력 재배치와 고용 계획을 세울 수 있었다. Excel Solver로 정수 계획법을 사용하여 혁신된 프로세스에 필요한 최적 인력을 산출하였고 그를 바탕으로 인건비를 최소화하는 결과를 얻을 수 있었다. 그러나 정수 계획법으로는 고객이 매 서브 프로세스마다 대기해야 하는 시간을 고려하지 못하여 고객 만족도가 저하되는 걸 막을 수 없는 인력 운영 전략을 세우게 되기에 Arena를 사용하여 대기 시간을 최대한 줄이도록 시뮬레이션을 하였고 최적적으로 적정 인력과 인건비를 산정하였다. 그 결과 요구되는 인력과 인건비는 현저하게 줄어들었고 고객의 대기 시간도 크게 감소한 것을 볼 수 있었다. 프로세스에 이슈가 발생하는 회사들은 프로세스 혁신을 단행하고 최적화 기법이나 시뮬레이션을 사용하여 비용 감소와 효율성 증대를 추구할 수 있다