An adaptive control algorithm for variable stiffness antagonistic joints

학위논문 (석사)-- 서울대학교 대학원 : 기계항공공학부, 2014. 2. 박종우.In this thesis, we consider the problem of estimating nonlinear stiffness of flexible transmissions in single link robots with antagonistic variable stiffness actuation. Joint stiffness estimation is obtained using an adaptive control algorithm. For the joint stiffness estimation, we assume that all rigid body dynamic parameters of robot except stiffness are known value. The motor position, velocity, link angle position, velocity and flexibility torque are assumed to be measurable for the state-feedback. An adaptive control algorithm with input-output linearization state feedback is used in our problem on the basis that this algorithm is optimal for our problem. Joint stiffness value is assumed to be intrinsically a nonlinear polynomial function of the deformation. Simulation results from performed of single link arm robots are reported, showing a good performance in trajectory tracking of link angle position and in estimating a nonlinear polynomial function of the joint stiffness.1. Introduction 2. Dynamic modeling 3. Adaptive variable stiffness control algorithm 3.1 Review of linearized techniques 3.2 Adaptive control of the SISO system 4. Simulation 4.1 Simulation Setup 4.2 Simulation Results 5 ConclusionMaste

Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients

Telomerase reverse transcriptase (TERT) is the reverse transcriptase component of the telomeric complex, which synthesizes terminal DNA to protect chromosomal ends and to maintain genomic integrity. In melanoma, mutation in TERT promoter region is a common event and theses promoter variants have been shown to be associated with increased gene expression, decreased telomere length and poorer outcome. In this study, we determined the frequency of TERT promoter mutation in 88 Korean primary melanoma patients and aimed to see the association of TERT promoter mutation status to other major molecular features, such as BRAF, NRAS, KIT mutations and correlate with clinicopathological features. In our study, acral melanoma (n=46, 52.3%) was the most common type. Overall, TERT promoter mutation was observed in 15 cases (17%) with ten c. -124C>T altertions and five c. -146C>T alterations. None of our samples showed CC>TT mutation which is considered pathognomonic of UV induction. Among the 46 acral melanoma patients, 5 patients (10.9%) harbored TERT promoter mutation. Tumors with TERT promoter mutation showed significantly greater Breslow thickness compared to WT tumors (P=0.039). A combined analysis for the presence of TERT promoter and BRAF mutations showed that patients with both TERT promoter and BRAF mutation showed decreased survival compared with those with only TERT promoter mutation, only BRAF mutation, or without mutations in either TERT promoter or BRAF (P=0.035). Our data provides additional evidence that UV-induced TERT promoter mutation frequencies vary depending on melanoma subtype, but preserves its prognostic value.ope

PTEN Methylation Dependent Sinonasal Mucosal Melanoma

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.ope

Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy

PURPOSE: The purpose of this study is to investigate the prognostic significance of SOX2 gene amplification and expression in patients with American Joint Committee on Cancer stage III lung squamous cell carcinoma (SCC) who underwent surgery followed by adjuvant radiotherapy. MATERIALS AND METHODS: Pathological specimens were obtained from 33 patients with stage III lung SCC treated with surgery followed by adjuvant radiotherapy between 1996 and 2008. SOX2 gene amplification and protein expression were analyzed using fluorescent in situ hybridization and immunohistochemistry, respectively. Patients were divided into two groups according to their SOX2 gene amplification and protein expression status. Kaplan-Meier estimates and a Cox proportional hazards model were used to identify the prognostic factors affecting patient survival. RESULTS: The median follow-up period for surviving patients was 58 months (range, 5 to 102 months). SOX2 gene amplification was observed in 22 patients and protein overexpression in 26 patients. SOX2 overexpression showed significant association with SOX2 gene amplification (p=0.002). In multivariate analysis, SOX2 overexpression was a significant prognostic factor for overall survival (OS) (hazard ratios [HR], 0.1; 95% confidence interval [CI], 0.002 to 0.5; p=0.005) and disease-free survival (DFS) (HR, 0.15; 95% CI, 0.04 to 0.65; p=0.01). Age (HR, 0.33; 95% CI, 0.11 to 0.98; p=0.046) and total radiation dose (HR, 0.13; 95% CI, 0.02 to 0.7; p=0.02) were the independent prognostic factors for OS and DFS. Patients with SOX2 amplification did not show a longer OS (p=0.95) and DFS (p=0.48). CONCLUSION: Our data suggested that SOX2 overexpression could be used as a positive prognostic factor in patients with stage III lung SCC receiving adjuvant radiotherapy.ope

CpG Island Methylator Phenotype and Methylation of Wnt Pathway Genes Together Predict Survival in Patients with Colorectal Cancer

PURPOSE: Dysregulation of the Wnt pathway is a crucial step in the tumorigenesis of colorectal cancer (CRC). This study aimed to determine whether DNA methylation of Wnt pathway genes helps predict treatment response and survival in patients with metastatic or recurrent CRC. MATERIALS AND METHODS: We retrospectively collected primary tumor tissues from 194 patients with metastatic or recurrent CRC. Pyrosequencing was used to examine the methylation of 10 CpG island loci in DNA extracted from formalin-fixed paraffin-embedded specimens. To elucidate the predictive role of DNA methylation markers, Kaplan-Meier survival estimation and Cox regression were performed for progression-free survival and overall survival (OS). RESULTS: The methylation frequencies of the 10 genes analyzed (p16, p14, MINT1, MINT2, MINT31, hMLH1, DKK3, WNT5A, AXIN2, and TFAP2E) were 47.9%, 10.8%, 21.1%, 16.0%, 20.6%, 0.5%, 53.1%, 32.0%, 2.6%, and 2.1%, respectively. We divided patients into three groups based on the number of methylated genes (group 1, no methylation n=38; group 2, 1-2 methylations n=92; group 3, 3 or more methylations n=64). Among patients treated with palliative chemotherapy (n=167), median OSs of groups 1, 2, and 3 were 39.1, 39.7, and 29.1 months, respectively (log rank p=0.013). After adjustment, number of methylations was identified as an independent poor prognostic factor (0-2 methylated vs. ≥3 methylated: hazard ratio, 1.72; 95% confidence interval, 1.16-2.56, p=0.007). CONCLUSION: This study suggests that methylation of Wnt pathway genes, in addition to known CpG island methylator phenotype markers, may help predict treatment outcome and survival in patients with CRC.ope

Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites

Peritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We identified a unique mutational signature biased toward C-to-A substitutions in malignant ascites. In contrast, the patients who received treatment of adjuvant chemotherapy showed a high rate of C-to-T substitutions along with hypermutation in malignant ascites. Comparative analysis revealed several candidate mutations for GC peritoneal carcinomatosis: recurrent mutations in COL4A6, INTS2, and PTPN13; mutations in druggable genes including TEP1, PRKCD, BRAF, ERBB4, PIK3CA, HDAC9, FYN, FASN, BIRC2, FLT3, ROCK1, CD22, and PIK3C2B; and mutations in metastasis-associated genes including TNFSF12, L1CAM, DIAPH3, ROCK1, TGFBR1, MYO9B, NR4A1, and RHOA. Notably, gene ontology analysis revealed the significant enrichment of mutations in the Rho-ROCK signaling pathway-associated biological processes in malignant ascites. At least four of the eight patients acquired somatic mutations in the Rho-ROCK pathway components, suggesting the possible relevance of this pathway to GC peritoneal carcinomatosis. These results provide a genome-wide molecular understanding of GC peritoneal carcinomatosis and its clinical implications, thereby facilitating the development of effective therapeutics.ope

Changes in telomerase activity due to alternative splicing of human telomerase reverse transcriptase in colorectal cancer

Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. The present study analyzed hTERT splicing patterns with respect to hTERT and telomerase activity in colorectal cancer. Telomerase activity was determined by telomeric repeat amplification protocol assay, and spliced variants of hTERT were identified by reverse transcription-polymerase chain reaction in 40 colorectal cancer tissue samples. In the lower range of telomerase activity (0-100 units), the percentage of the β variant decreased with the increment in telomerase activity, whereas in the higher range of telomerase activity (>100 units), total hTERT expression level revealed a trend toward increment. There was a positive correlation between the full-length variant level and β variant level. Conversely, there was a negative correlation between the percentage of the full-length variant and β variant. Tumor-node-metastasis stage was the strongest prognostic factor in multivariate analysis and the percentage of the full-length variant was an independent prognostic factor for survival. Telomerase activity was primarily altered with changes in alternative splicing of the full-length and β variants of hTERT in colorectal cancer.ope

Prognostic implications of PIK3CA amplification in curatively resected liposarcoma

BACKGROUND: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. PATIENTS AND METHODS: A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). RESULTS: Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. CONCLUSIONS: We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.ope

Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer

We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay). Treatment was based on availability of targeted agents at the time of molecular diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC profiles were successfully achieved in 66 cases (81.5%); only IHC results were available for 15 cases. Eight cases received matched therapy based on sequencing results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor (n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n = 2), PI3Kβ inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%) cases were treated with matched and non-matched therapy, respectively. Matched therapy had significantly higher overall response rate than non-matched therapy (55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in identifying patients who may benefit from targeted therapies.ope

(A) STUDY ON THE EFFECT OF MATERNITY'S KNOWLEDGE ABOUT AND ATTITUDES TOWARDS NUTRITION HAVE ON THE INFANTS' DEGREE OF HEALTHINESS

영유아기는 성장발달의 중요한 시기로서 이때의 건강은 매우 중요하며 평생의 건강을 좌우할수 있는 결정적인 시기이다. 따라서 본 연구는 유아기(幼兒期)의 건강에 있어 중요한 역할을 하는 어머니의 영양지식과 태도를 측정하고 그것이 유아의 건강도에 미치는 영향을 파악해서 앞으로의 보건영양교육을 수행하는 데 있어서 효과적이고 바람직한 방향으로 이끌어갈 수 있는 기초 자료로 활용하려는데 그 목적을 두었다. 본 연구는 서울시내에 거주하며 유아기에 해당하는 자녀를 가진 453명의 어머니를 대상으로 설문지 방법에 의해 실시되었으며 그 결과는 다음과 같다. 1 . 어머니의 영양지식은 연령이 낮을수록, 교육수준이 높을수록, 식생활비, 월총수입이 많을수록 영양지식 수준이 높아지는 경향을 보였으며(p＜0.05), 또 직업경험이 있는쪽이, 영양에 대해 배운경험이 있는 쪽이, 그리고 학교와 영양학자에게서 영양정보를 얻는 쪽이 영양지식 수준이 높았다. 영양에 관한 태도는 고등학교 졸업인 어머니가 가장 좋게 나타났으며 의사에게서 영양정보를 얻는 어머니가 가장 좋게 나타났다. 2 . 유아의 건강도는 어머니의 일반적 특성중 교육수준, 월 총수입, 가족수, 영양지식의 급원이 영향을 주는 것으로 나타났다.(p＜0.05) 어머니의 교육수준이 높을수록, 소득이 많을수록 유아의 건강도가 높았으며(p＜0.01) 3인가족이 유아의 건강도가 가장 높고 학교와 영양학자에게서 영양정보를 얻는 어머니에게서 유아의 건강도가 가장 높았다. 3 . 유아의 일반적 특성중 성별과 형제서열이 유아의 건강도에 영향을 주는 것으로 나타났다.(p＜0.05) 성별에서는 여아쪽이 건강도가 높았으며 형제서열에서는 장녀가 아닌 경우가 건강도가 가장 높았다. 4 . 어머니의 영양지식 및 태도가 유아의 건강도에 영향을 주는 것으로 나타났으며(p＜0,001), 영양지식에 관한 영양소, 식품구성, 균형식, 질병의 4항목중 특히 식품구성과 균형식에 대한 항목이 영향을 주는 것으로 나타났다.(p＜0.05) 5 . 영양지식과 태도와 건강도와의 관계에서는 어머니의 영양지식이 높을수록 유아의 건강도가 높고(P＜0.001), 영양에 관한 태도가 좋을수록 유아의 건강도가 높은것으로 나타났다.(p＜0.01) 그러나 유아의 건강도와 어머니의 영양지식, 건강도와 태도와의 상관관계에서는 서로 비슷한 상관관계를 보였다. 이상과 같은 결과에서 어린이의 건강증진을 위해서는 아동의 식습관 형성과 건강에 중대한 영향을 미치는 어머니들을 대상으로 하는 보다 효과적인 영양교육방안이 마련되어야 할 것이다.;Babyhood (or infanthood) is a very important period of growth ＆ development, hence the health during this period is crucial and also can affect the health of entire life. Accordingly, in this study the research measured the mothers' knowledge about nutrition ＆ attitudes towards nutrition which play an important role in deciding the health of infants during their infanthood, and by figuring out the effect which these knowledge ＆ attitudes have on the infants' degree of healthiness, the research tried to use these data as a basic material which can be effective ＆ helpful to the implementation of health ＆ nutrition-education from now on. This survey was implemented, setting as its target 453 mothers who were residing in Seoul city ＆ having childrens of infanthood, and questionnaire method was used for this survy. The results can be summarized as follows; 1. As far as the mothers' knowledge about nutrition was concerned, the lower the age, the higher the degree of education was, the larger their monthly income ＆ food expense were, they showed a tendancy of higher degree of awareness ＆ knowledge about nutrition(P＜0.05). And also, the mothers, who had job experiences, who had the experience of learning about nutrition and who acquired the nutrition-information from schools or nutritionists, showed a higher degree of knowledge about nutrition. As far as the attitude towards nutrition was concerned, the mothers who graduated from high school and the mothers who acquired nutrition-information from doctors, showed the best result. 2. It was shown that the infants' degree of healthiness was affected by the degree of education, their families' monthly income, number of family members and by the supplying source of their nutrition information(P＜0.05) among mothers' general characteristics. The higher the mothers' degree of education, the higher the family's income, the infants showed a higher degree of healthiness(P＜0.01), and the infants of the families with 3 family members and whose mothers acquired nutrition knowledge ＆ information from nutritionists and from schools showed the highest degree of healthiness. 3. Among the general characteristics of infants, their sexes ＆ their rank in their brothers ＆ sisters seemed to affect their degree of healthiness(P＜0.05). According to sexes, girl-infants showed a higher degree of healthiness, and according to the infants' rank in their brothers ＆ sisters, the infants who were not an eldest daughter showed the best result. 4. Mothers' knowledges about ＆ attitudes towards nutrition were shown to affect the infants' degree of healthiness(P＜0.001), and among 4 items of nutrition-knowledge(nutrient, composition of food, balanced meal and disease), especially the food composition ＆ balanced meal showed a greater effect on the infants' degree of healthiness(P＜0.05). 5. As far as the relations(correlations) between the degree of healthiness and knowledges about ＆ attitudes towards nutrition were concerned, the higher the mothers' knowledges about nutrition, their infants showed a higher degree of healthiness(P＜0.001), and the better the mothers' attitudes towards their infants' nutrition, their infants showed a higher degree of healthiness(P＜0.01). But infants' degree of healthiness ＆ their mothers' knowledges about nutrition, and their mothers' attitudes towards nutrition ＆ the degree of healthiness, showed a similar correlation.논문개요 = ⅷ Ⅰ. 서론 = 1 A. 문제의 제기 = 1 B. 연구 목적 = 4 C. 가설의 설정 = 5 D. 용어의 정의 = 6 E. 연구의 제한점 = 7 Ⅱ. 이론적 배경 및 선행연구 = 8 A. 유아기의 발육발달과 영양 = 8 B. 대상별 영양지식의 현황 = 14 C. 영양면에서 어머니가 자녀에게 미치는 영향 = 18 D. 영양교육의 필요성 = 22 E. 본 연구의 이론적 기틀(연구에 사용된 변수의 내용) = 24 Ⅲ. 연구 방법 = 25 A. 연구 대상 = 25 B. 자료수집기간 및 방법 = 25 C. 연구도구 및 연구내용 = 25 D. 자료처리 및 분석방법 = 26 Ⅳ. 연구결과 및 고찰 = 28 A. 조사 대상자의 일반적 특성 = 28 B. 모성의 일반적 특성이 영양지식 및 태도에 미치는 영향 = 42 C. 모성의 일반적 특성이 유아의 건강도에 미치는 영향 = 50 D. 유아의 일반적 특성이 유아의 건강도에 미치는 영향 = 52 E. 모성의 영양지식 및 태도가 유아의 건강도에 미치는 영향 = 55 Ⅴ. 결론 및 제언 = 60 참고문헌 = 63 ABSTRACT = 6