Development and Validation of a Novel Plasma Protein Signature for Breast Cancer Diagnosis by Using Multiple Reaction Monitoring-based Mass Spectrometry.

Lee, Han-Byoel,Kang, Un-Beom,Moon, Hyeong-Gon,Lee, Jiwoo,Lee, Kyung-Min,Yi, Minju,Park, Yong Sun,Lee, Jong Won,Yu, Jong-Han,Choi, Seung Ho,Cho, Sang Heon,Lee, Cheolju,Han, Wonshik,Noh, Dong-Young Potamitis Press 2015 Anticancer research Vol.35 No.11

<P>We aimed to develop a plasma protein signature for breast cancer diagnosis by using multiple reaction monitoring (MRM)-based mass spectrometry.</P>

Effects of clioquinol analogues on the hypoxia-inducible factor pathway and intracelullar mobilization of metal ions.

Kim, So Yeon,Lee, Myong Jin,Kim, Jeong Won,Na, Yu-Ran,Lee, Ho-Youl,Cho, Hyunju,Lee, Keun Byeol,Lee, You Mie,Lee, Cheolju,Park, Hyunsung,Yang, Eun Gyeong Pharmaceutical Society of Japan 2012 Biological & pharmaceutical bulletin Vol.35 No.12

<P>We previously found that clioquinol (CQ) increases functional hypoxia-inducible factor-1α (HIF-1α) with enhanced transcription of its target genes. Here we report that compounds derived from 8-hydroxyquinoline including CQ, broxyquinoline (BQ), iodoquinol (IQ) and chloroacetoxyquinoline (CAQ) promote neovascularization effectively based on chick chorioallantoic membrane assays. The CQ analogues induce stabilization of HIF-1α as well as enhance HIF-1-mediated vascular endothelial growth factor transcription. These analogues also exert inhibitory effects on the activity of prolyl and asparaginyl hydroxylations of HIF-1α in vitro. Despite metal ion-dependent restoration of the inhibited HIF-1α hydroxylase activity, the cellular HIF-1α-inducing effects of the CQ analogues are reversed to varying degrees by Zn(2+) and Fe(2+). While CQ and BQ are completely reversed by Zn(2+), co-administration of Zn(2+) and IQ has only a partial reversing effect. On the other hand, CAQ-mediated stabilization of HIF-1α is reversed by Fe(2+) but not by Zn(2+). These phenomena are found to coincide with elevation of the intracellular Zn(2+) and Fe(2+) levels by the CQ analogues, suggesting that metal ion effects on HIF-1α in cells likely reflect the differential transporting capability of the analogues.</P>

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein

Seungbum Choi,Yae Eun Park,Eun Jeong Cheon,Kyeong Yeon Kim,Miso Kim,Soo-jin Ann,Hye-Min Noh,Jae Ho Lee,Chan-Joo Lee,Seung-Taek Lee,Cheolju Lee,Ji Eun Lee,Sang-Hak Lee 대한심장학회 2020 Korean Circulation Journal Vol.50 No.3

Background and Objectives: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL. Methods: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio. Results: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories. Conclusions: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity

Lee, Youngjin,Kim, Byoung Sik,Choi, Sanghyeon,Lee, Eun-Young,Park, Shinhye,Hwang, Jungwon,Kwon, Yumi,Hyun, Jaekyung,Lee, Cheolju,Kim, Jihyun F.,Eom, Soo Hyun,Kim, Myung Hee National Academy of Sciences 2019 Proceedings of the National Academy of Sciences Vol.116 No.36

<P><B>Significance</B></P><P>MARTX toxins present across multiple bacterial genera are primary virulence factors that facilitate initial colonization, dissemination, and lethality in a wide range of hosts, including humans. Upon entry into host cells, the toxins undergo a processing event to release their disease-related modularly structured effector domains. However, the mechanisms underlying processing and activation of diverse effector domains within the toxins remain unclear. Here, we use biochemical and structural biological approaches, in combination with cellular microbiological experiments, to demonstrate how Makes caterpillars floppy-like effector (MCF) or its homolog-containing MARTX toxins process effector modules and fully activate effectors. MCF-containing toxins target ADP-ribosylation factor proteins ubiquitously expressed in cells to activate and disseminate effectors across subcellular compartments simultaneously, eventually leading to systemic pathogenicity.</P><P>Upon invading target cells, multifunctional autoprocessing repeats-in-toxin (MARTX) toxins secreted by bacterial pathogens release their disease-related modularly structured effector domains. However, it is unclear how a diverse repertoire of effector domains within these toxins are processed and activated. Here, we report that Makes caterpillars floppy-like effector (MCF)-containing MARTX toxins require ubiquitous ADP-ribosylation factor (ARF) proteins for processing and activation of intermediate effector modules, which localize in different subcellular compartments following limited processing of holo effector modules by the internal cysteine protease. Effector domains structured tandemly with MCF in intermediate modules become disengaged and fully activated by MCF, which aggressively interacts with ARF proteins present at the same location as intermediate modules and is converted allosterically into a catalytically competent protease. MCF-mediated effector processing leads ultimately to severe virulence in mice via an MCF-mediated ARF switching mechanism across subcellular compartments. This work provides insight into how bacteria take advantage of host systems to induce systemic pathogenicity.</P>

압밀해석을 통한 부마찰이 작용하는 단독말뚝의 거동분석

이철주(Lee Cheolju) 한국지반환경공학회 2009 한국지반환경공학회논문집 Vol.10 No.2

본 연구에서는 2차원 유한요소해석을 통하여 부마찰(negative skin friction) 이 작용하는 단독말뚝의 거동을 분석하였다. 압밀의 진행에 따른 부마찰의 변화를 검토하기 위하여 압밀해석을 실시하였으며, 말뚝과 주변지반 사이에서의 항복(yielding, slip)을 고려하였다. 일반적으로 널리 사용되는 -방법에 의해 부마찰력을 산정하는 경우 중립면 부근에서의 전단강도의 부분발현 및 지중응력의 감소를 반영할 수 없기 때문에 정밀유한요소 해석에 비하여 부마찰력이 25% 정도 과하게 평가된다. 압밀이 진행 중일 때 말뚝과 지반사이 대부분의 구간에서 항복이 발생하는 경우 더 이상의 부마찰력의 증가는 그리 크지 않은 것으로 나타났다. 부마찰이 발생하는 말뚝에 코팅을 실시하는 경우 부마찰력의 크기 및 말뚝의 침하를 효과적으로 감소시킬 수 있으나, 말뚝두부에 상재하중이 작용할 때 말뚝의 선단이 충분히 견고한 지지층에 설치되어 있지 않은 경우 말뚝의 마찰저항력이 매우 작아서 말뚝에 큰 침하가 발생할 우려가 있는 것으로 나타났다. A series of two-dimensional (2D) finite element analyses have been performed to study the behaviour of single piles in consolidating ground. The analysis was conducted based on coupled analyses by considering changes of pore water pressure in the clay. In the analyses the soil slippage at the pile and the soil interface has been included. The method widely used in practice somewhat overestimates dragload by about 25% compared to the rigorous numerical analysis since partial mobilization of skin friction near neutral plane and reductions in the vertical soil stress is not incorporated. When soil slip develops at most of the pile length at the pile-soil interface during consolidation, further increases in dragload is not significant. Application of coating on the pile surface can reduce dragload and pile settlement substantially, but under an axial load on the pile head very large pile settlement can be developed unless pile tip is located to a stiff bearing layer.

지하터파기로 인해 융기(Heaving)가 발생한 지반에 근입된 단독말뚝의 거동

이철주(Lee Cheolju) 한국지반환경공학회 2010 한국지반환경공학회논문집 Vol.11 No.1

본 연구에서는 유한요소해석을 실시하여 지반굴착으로 인해 융기(heaving)가 발생하는 지반에 사전에 근입된 말뚝의 거동에 대한 분석을 실시하였다. 수치해석에서는 말뚝과 점토사이 경계면에서의 미끄러짐(소성항복)을 고려하여 그 상호거동에 대하여 고찰하였다. 본 연구에서는 말뚝의 상향변위, 말뚝과 인접지반의 상대변위, 말뚝에 작용하는 전단응력 및 인장력을 분석하였다. 특히, 수직응력의 감소로 인해 말뚝과 인접지반에서의 전단응력이 전이되는 메커니즘에 대한 심도있는 분석을 실시하였다. 굴착에 의해 수직응력이 감소하여 말뚝과 인접지반 사이에서의 상대변위 및 전단응력이 변화하였다. 말뚝 대부분의 위치(Z/L=0.0-0.8)에서는 상향의 전단응력이 발생하였으나, 말뚝 선단부 부근(Z/L=0.8-1.0)에서는 하향의 전단응력이 발생하였고, 이로 인해 말뚝에는 인장력이 발생하였다, Z는 임의의 심도, L은 말뚝의 길이이다. 수치해석을 통해서 분석된 말뚝의 거동에 대하여 상세히 보고하였다. A finite element analysis has been conducted to clarify the behaviour of a single pile in heaving ground related to ground excavation. The numerical analysis has included soil slip at the pile-soil interface, analysing the interaction between the pile and the clay has been studied. The study includes the upward movement of the pile, the relative shear displacement between the pile and the soil and the shear stresses at the interface and the axial force on the pile. In particular, the shear stress transfer mechanism at the pile-soil interface related to a decrease in the vertical soil stress has been rigorously analysed. Due to the reductions in the vertical soil stress after excavation, the relative shear displacement and the shear stress along the pile have been changed. Upward shear stress developed at most part of the pile (Z/L=0.0-0.8), while downward shear stress is mobilized near the pile tip (Z/L=0.8-1.0) resulting in tensile force on the pile, where Z is the pile location and L is the pile length. Some insights into the pile behaviour in heaving ground analysed from the numerical analyses has been reported.

Web 기반 컨텐츠 제공 시스템 모델

이철주(Cheolju Lee),정기원(Kiwon Chong) 한국정보과학회 2000 한국정보과학회 학술발표논문집 Vol.27 No.2Ⅰ

인터넷 정보서비스의 다양화와 전자상거래의 활성화로 다양한 CP(Contents Provider)들이 등장하고 인터넷 비즈니스 모델에 유료 컨텐츠 제공을 통한 컨텐츠 비즈니스가 새로운 수익 모델로 등장 하게 되었다. 이러한 추세에 발을 맞추어 컨텐츠에 대한 정보이용료 처리를 수행하는 시스템의 필요성이 증대되고 있다. 기존의 PC 통신의 IP(Information Provider)들은 텍스트 위주의 분당 사용료에 따른 종량제 서비스를 제공하여 수익을 올릴 수 있었지만 CP들은 그렇지 못했다[9]. PC 통신을 통해 정보를 제공하는 IP와 인터넷을 통해 정보를 제공하는 CP의 특징으로 기존 CP 제공 유형은 인터넷상의 정보 사용료 처리부분에 대한 수익금 정산처리의 어려움으로 IP방법을 모방하고 있다. 따라서 본 논문은 CP 특징을 이용하여 독자적인 홈페이지 운영으로 유료 정보 이용에 대한 이용료 부과 시스템 모델을 제안한다.

마르미 - Ⅱ 방법론을 적용한 ERP패키지 개발 프로세스

이철주(Cheolju Lee),허분애(Boonae Heo),최용락(Yonglak Choi),정기원(Kiwon Chong) 한국정보과학회 1999 한국정보과학회 학술발표논문집 Vol.26 No.2Ⅰ

현재 기업의 정보시스템으로 각광 받고있는 ERP 시스템은 인사, 회계, 물류, 제조, 서비스 등 기업 활동의 전 부분을 효과적으로 관리하고 통제하기 위한 통합 정보시스템으로 ERP 패키지를 이용하여 최신의 정보기술을 지원하는 비즈니스 시스템을 말한다. 기존의 정보시스템 개발에서는 명확한 사용자 요구사항을 기반으로 하지만 ERP 패키지 개발에서는 사용자 요구사항을 정의하는데 어려움이 많다. 따라서 기존의 시스템에 적용되는 방법론과는 달리 ERP 패키지 개발을 위한 방법론이 필요하다. 본 논문에서는 고품질의 ERP 패키지를 효율적으로 설계할 수 있도록 마르미-Ⅱ에 기반한 ERP 패키지 개발 프로세스를 제안한다.

단독말뚝의 측면으로 시공되는 터널에 의한 말뚝의 거동 연구

이철주(Lee Cheolju) 한국지반환경공학회 2011 한국지반환경공학회논문집 Vol.12 No.1

본 연구에서는 단독말뚝의 측면에서 시공되는 터널에 의한 말뚝의 거동에 대하여 3차원 수치해석을 통하여 분석하였다. 수치해석을 통하여 터널-말뚝-지반의 상호거동에 대한 심도 있는 분석을 실시하였다. 수치해석을 통해 말뚝의 침하, 말뚝과 주변지반 사이의 상대변위, 전단응력 및 말뚝의 축력변화를 고찰하였다. 특히 터널굴착에 의한 전단응력의 전이과정에 대한 심도 있는 분석을 실시하였다. 터널굴착에 의한 말뚝과 인근지반에서의 상대변위 변화로 인하여 말뚝에 작용하는 전단응력 및 축력의 분포가 변하게 되는 것으로 나타났다. 터널 중심부의 상부에서는 하향의 전단응력이 발생하는 반면(Z/L=0.0-0.7~0.8), 그 하부에서는 (Z/L=0.7~0.8-1.0) 상향의 전단응력이 발생하여 말뚝에 압축력이 발생된다, 이때 Z는 임의의 심도, L은 말뚝의 길이다. 터널굴착이 종료된 후 말뚝에는 최대 0.475Pa의 압축력이 발생하였다, 이때 Pa는 말뚝의 설계지지력이다. 수치해석을 통해서 도출된 터널굴착이 말뚝 거동에 미치는 영향에 대해 상세히 고찰하였다. Three-dimensional(3D) numerical analyses have been conducted to study the behaviour of a single pile to adjacent tunnelling conducted in the lateral direction of the pile. In the numerical analyses, the interaction between the tunnel, the pile and the soil next to the pile has been analysed. The study includes the pile settlement, the relative shear displacement between the pile and the soil, the shear stresses at the soil next to the pile and the axial force on the pile. In particular, the shear stress transfer mechanism along the pile related to the tunnel advancement has been rigorously analysed. Due to changes in the relative shear displacement between the pile and the soil next to the pile during the tunnel advancement, the shear stress and the axial force distributions along the pile have been changed. Downward shear stress developed above the tunnel springline (Z/L=0.0-0.7~0.8), while upward shear stress is mobilised below the tunnel springline (Z/L=0.7~0.8-1.0) resulting in compressive force on the pile, where Z is the pile location and L is the pile length. Maximum compressive force of about 0.475Pa was developed on the pile after completion of tunnel advancement, where Pa is the allowable pile capacity. Some insights into the pile behaviour to tunnelling obtained from the numerical analyses will be reported and discussed.

CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3

Seo, Jinho,Lee, Eun-Woo,Sung, Hyerim,Seong, Daehyeon,Dondelinger, Yves,Shin, Jihye,Jeong, Manhyung,Lee, Hae-Kyung,Kim, Jung-Hoon,Han, Su Yeon,Lee, Cheolju,Seong, Je Kyung,Vandenabeele, Peter,Song, Jae Nature Publishing Group 2016 NATURE CELL BIOLOGY Vol. No.

<P>Receptor-interacting protein kinase 3 (RIPK3) functions as a key regulator of necroptosis. Here, we report that the RIPK3 expression level is negatively regulated by CHIP (carboxyl terminus of Hsp70-interacting protein; also known as STUB1) E3 ligase-mediated ubiquitylation. Chip(-/-) mouse embryonic fibroblasts and CHIP-depleted L929 and HT-29 cells exhibited higher levels of RIPK3 expression, resulting in increased sensitivity to necroptosis induced by TNF (also known as TNF alpha). These phenomena are due to the CHIP-mediated ubiquitylation of RIPK3, which leads to its lysosomal degradation. Interestingly, RIPK1 expression is also negatively regulated by CHIP-mediated ubiquitylation, validating the major role of CHIP in necrosome formation and sensitivity to TNF-mediated necroptosis. Chip(-/-) mice (C57BL/6) exhibit inflammation in the thymus and massive cell death and disintegration in the small intestinal tract, and die within a few weeks after birth. These phenotypes are rescued by crossing with Ripk3(-/-) mice. These results imply that CHIP is a bona fide negative regulator of the RIPK1-RIPK3 necrosome formation leading to desensitization of TNF-mediated necroptosis.</P>