• 한국자기공명학회논문지
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• 제20권4호
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• pp.138-142
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• 2016

Replication Protein A (RPA) is the eukaryotic single-stranded DNA binding protein. It involves in DNA replication, repair, and damage response. Among three subunits, RPA70 has a protein-protein binding domain (RPA70N) at the N-terminal. It has known that the domain recruits several damage response proteins to the damaged site. Also, it is suggested that there are more candidates that interact with RPA70N. Even though several studies performed on the structural aspects of RPA70N and its ligand binding, the backbone assignments of RPA70N is not available in public. In this study, we present the backbone assignments of RPA70N.

• 한국자기공명학회논문지
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• 제20권3호
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• pp.66-70
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• 2016

The replication protein A (RPA), is a heterotrimer with 70, 32 and 14 kDa subunits and plays a crucial role in DNA replication, recombination, and repair. The largest subunit, RPA70, binds to single-stranded DNA (ssDNA) and mediates interactions with many cellular and viral proteins. In this study, we performed nuclear magnetic resonance experiments on the complex of the DNA binding domain A of human RPA70 (RPA70A) with ssDNA, d(CCCCC), at various temperatures, to understand the temperature dependency of ssDNA binding affinity of RPA70A. Essential residues for ssDNA binding were conserved while less essential parts were changed with the temperature. Our results provide valuable insights into the molecular mechanism of the ssDNA binding of human RPA.

• 한국자기공명학회논문지
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• 제22권1호
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• pp.18-25
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• 2018

Replication protein A (RPA) is an essential single-stranded DNA binding protein in DNA processing. It is known that N terminal domain of RPA70 (RPA70N) recruits various protein partners including damage-response proteins such as p53, ATRIP, Rad9, and MRE11. Although the common binding residues of RPA70N were revealed, dynamic properties of the protein are not studied yet. In this study, we measured $^{15}N$ relaxation parameters ($T_1,\;T_2$ and heteronuclear NOE) of human RPA70N and analyzed them using model-free analysis. Our data showed that the two loops near the binding site experience fast time scale motion while the binding site does not. It suggests that the protein binding surface of RPA70N is mostly rigid for minimizing entropy cost of binding and the loops can experience conformational changes.

• 한국자기공명학회논문지
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• 제20권3호
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• pp.71-75
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• 2016

The replication protein A (RPA) plays a crucial role in DNA replication, recombination, and repair. RPA consists of 70, 32 and 14 kDa subunits and has high single-stranded DNA (ssDNA) binding affinity. The largest subunit, RPA70, mainly contributes to bind to ssDNA as well as interact with many cellular and viral proteins. In this study, we performed nuclear magnetic resonance experiments on the complex of the DNA binding domain A of human RPA70 (RPA70A) with ssDNA, d(CCCCC), at various pH, to understand the effect of pH on the ssDNA binding of RPA70A. The chemical shift perturbations of binding residues were most significant at pH 6.5 and they reduced with pH increment. This study provides valuable insights into the molecular mechanism of the ssDNA binding of human RPA.

• BMB Reports
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• 제35권2호
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• pp.194-198
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• 2002

Eukaryotic replication protein A (RPA) is a single-stranded(ss) DNA binding protein with multiple functions in DNA replication, repair, and genetic recombination. The 70-kDa subunit of eukaryotic RPA contains a conserved four cysteine-type zinc-finger motif that has been implicated in the regulation of DNA replication and repair. Recently, we described a novel function for the zinc-finger motif in the regulation of human RPA's ssDNA binding activity through reduction-oxidation (redox). Here, we show that yeast RPA's ssDNA binding activity is regulated by redox potential through its RPA32 and/or RPA14 subunits. Yeast RPA requires a reducing agent, such as dithiothreitol (DTT), for its ssDNA binding activity. Also, under non-reducing conditions, its DNA binding activity decreases 20 fold. In contrast, the RPA 70 subunit does not require DTT for its DNA binding activity and is not affected by the redox condition. These results suggest that all three subunits are required for the regulation of RPA's DNA binding activity through redox potential.

• Radiation Oncology Journal
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• 제27권3호
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• pp.140-144
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• 2009

목 적: 전이성 뇌종양 환자에서 전뇌조사를 시행받은 160명의 환자를 대상으로 원발 종양 가중치에 따른 생존율을 후향적으로 분석해보고자 하였다. 대상 및 방법: 2002년부터 2008년 사이에 인하대병원에서 전이성 뇌종양으로 진단받은 암환자들 중 전뇌 조사 방사선 치료 30 Gy를 받은 160명의 환자를 대상으로 후향적으로 분석하였다. 원발성 종양이 유방암인 경우는 20명, 폐암인 경우는 103명이었다. 160명의 환자 중 척수 연수막 전이(leptomeningeal seeding) 환자를 제외한, 142명의 환자를 대상으로 예후 인자 및 Recursive Partitioning Aanalysis (RPA) 분류에 따른 생존율, 중앙생존기간과, RPA 분류에 원발 종양의 종류에 따라 가중치를 둔 새로운 Weighted Partitioning Analysis (WPA) 분류에 따른 생존율과 중앙생존기간을 분석하였고 RPA분류와 비교 분석하였다. 결 과: RPA분류에 의한 중앙생존기간은 분류 I (8명), 분류 II (76명), 분류 III (58명)가 각각 20.0개월, 10.0개월, 3.0개월이었으며(p=0.003), WPA 분류의 경우에는 분류 I (3명), 분류 II (9명), 분류 III (70명), 분류 IV (60명)가 각각 36개월, 23.7개월, 10.9개월, 8.6개월로(p=0.001) RPA 분류보다 더 우위성을 보였다. 결 론: 새로운 예후 지표인 WPA 분류가 기존의 RPA 분류보다 전이성 뇌종양 환자에서 치료 방침을 결정함에 있어 도움을 줄 것으로 생각된다.

• International Journal of Vascular Biomedical Engineering
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• 제1권2호
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• pp.36-41
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• 2003

Both flow visualizations and computational fluid dynamics were performed to determine hemodynamics in a total cavopulmonary connection (TCPC) model for surgically correcting congenital heart defects. From magnetic resonance images, an anatomically correct glass model was fabricated to visualize steady flow. The total flow rates were 4, 6 and 8L/min and flow rates from SVC and IVC were 40:60. The flow split ratio between LPA and RPA was varied by 70:30, 60:40 and 50:50. A pressure-based finite-volume software was used to solve steady flow dynamics in TCPC models. Results showed that superior vena cava(SVC) and inferior vena cava(IVC) flow merged directly to the intra-atrial conduit, creating two large vortices. Significant swirl motions were observed in the intra-atrial conduit and pulmonary arteries. Flow collision or swirling flow resulted in energy loss in TCPC models. In addition, a large intra-atrial channel or a sharp bend in TCPC geometries could influence on energy losses. Energy conservation was efficient when flow rates in pulmonary branches were balanced. In order to increase energy efficiency in Fontan operations, it is necessary to remove a flow collision in the intra-atrial channel and a sharp bend in the pulmonary bifurcation.

• International Journal of Vascular Biomedical Engineering
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• 제2권1호
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• pp.11-16
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• 2004

Both flow visualizations and computational fluid dynamics were performed to determine hemodynamics in a total cavopulmonary connection (TCPC) model for surgically correcting congenital heart defects. From magnetic resonance images, an anatomically correct glass model was fabricated to visualize steady flow. The total flow rates were 4, 6 and 8L/min and flow rates from SVC and IVC were 40:60. The flow split ratio between LPA and RPA was varied by 70:30, 60:40 and 50:50. A pressure-based finite-volume software was used to solve steady flow dynamics in TCPC models. Results showed that superior vena cava(SVC) and inferior vena cava(IVC) flow merged directly to the intra-atrial conduit, creating two large vortices. Significant swirl motions were observed in the intra-atrial conduit and pulmonary arteries. Flow collision or swirling flow resulted in energy loss in TCPC models. In addition, a large intra-atrial channel or a sharp bend in TCPC geometries could influence on energy losses. Energy conservation was efficient when flow rates in pulmonary branches were balanced. In order to increase energy efficiency in Fontan operations, it is necessary to remove a flow collision in the intra-atrial channel and a sharp bend in the pulmonary bifurcation.

• 대한의용생체공학회:학술대회논문집
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• 대한의용생체공학회 1996년도 춘계학술대회
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• pp.203-206
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• 1996

To understand the local fluid dynamics for different desists of Fontan operation, five models were made out of Pyrex glass to facilitate in-vitro study. Model I, II and III have same position of the center of the anastomosis of the IVC( inferior vena cava) with that of the SVC(superior vena cava), but Model IV and V have 10 mm offset between them. Also the anastomotic junction angles are different(Model I and $IV:90^{\circ}$, Model II and $V:70^{\circ}$, Model $III:45^{\circ}$). These models were then connected to a flow loop for flow visualization study. In Model I any dominant vortex was not seen in the central region of the juntion, but a large unstable vortex was created in the Model II and III. In Model IV and V a significant stagnation region was created in the middle of the offset region. It also showed that the flow direction from the IVC and SVC to the LPA(left pulmonary artery) and RPA(right pulmonary artery) highly depends on the offset of the junction rather than the anastomotic junction angle.

• Journal of Korean Neurosurgical Society
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• 제44권6호
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• pp.358-363
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• 2008

Objective : This study was performed to assess the efficacy of GKS in patients with ten or more brain metastases. Methods : From Aug 2002 to Dec 2007, twenty-six patients (13 men and 13 women) with ten or more cerebral metastatic lesions underwent GKS. The mean age was 55 years (32-80). All patients had Karnofsky performance status (KPS) score of 70 or better. According to recursive partitioning analysis (RPA) classification, 3 patients belonged to class I and 23 to class II. The location of primary tumor was lung (21), breast (3) and unknown (2). The mean number of the lesions per patient was 16.6 (10-37). The mean cumulated volume was 10.9 cc (1.0-42.2). The median marginal dose was 15 Gy (9-23). Overall survival and the prognostic factors for the survival were retrospectively analyzed by using Kaplan Meier method and univariate analysis. Results : Overall median survival from GKS was 34 weeks (8-199). Local control was possible for 79.5% of the lesions and control of all the lesions was possible in at least 14 patients (53.8%) until 6 months after GKS. New lesions appeared in 7 (26.9%) patients during the same period. At the last follow-up, 18 patients died; 6 (33.3%) from systemic causes, 10 (55.6%) from neurological causes, and 2 (11.1 %) from unknown causes. Synchronous onset in non-small cell lung cancer (p=0.007), high KPS score (${\geq}80$, p=0.029), and controlled primary disease (p=0.020) were favorable prognostic factors in univariate analysis. Conclusion : In carefully selected patients, GKS may be a treatment option for ten or more brain metastases.