Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain

Park, Hyunkyu,Kim, Donggeon,Kim, Eunmi,Sa, Jason K.,Lee, Hee Won,Yu, Suji,Oh, Jiwon,Kim, Seok-Hyung,Yoon, Yeup,Nam, Do-Hyun MDPI AG 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.9

<P>Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries. We characterized and evaluated the biochemical properties and tumor inhibitory effect of IRCR201 in vitro and in vivo. IRCR201 is a novel fully-human bivalent therapeutic antibody that exhibits cross-reactivity against both human and mouse c-Met proteins with high affinity and specificity. IRCR201 displayed low agonist activity and rapidly depleted total c-Met protein via the lysosomal degradation pathway, inhibiting c-Met-dependent downstream activation and attenuating cellular proliferation in various c-Met-expressing cancer cells. In vivo tumor xenograft models also demonstrated the superior tumor inhibitory responsiveness of IRCR201. Taken together, IRCR201 provides a promising therapeutic agent for c-Met-positive cancer patients through suppressing the c-Met signaling pathway and tumor growth.</P>

Development of a Dance Rehabilitation System using Kinect and a Vibration Feedback Glove

Hyunkyu Park,Jeongsoo Lee,Joonbum Bae 제어로봇시스템학회 2015 제어로봇시스템학회 국제학술대회 논문집 Vol.2015 No.10

Analysis of diffuse reflectivity of a highly disordered GaN nanostructure as an antireflection coating.

Park, Hyunkyu,Kim, Chinkyo Optical Society of America 2012 Optics letters Vol.37 No.4

<P>A highly disordered GaN nanostructure was grown by using hydride vapor phase epitaxy on an Si(100) substrate, and its diffuse reflectivity was measured in the 200-1200 nm spectral range by using an integrating sphere. A modified multiple-scattering-based model successfully explained the spectral distribution of diffuse reflectivity of this highly disordered GaN nanostructure.</P>

Antitumor activity, pharmacokinetics, tumor-homing effect, and hepatotoxicity of a species cross-reactive c-Met antibody

Park, Hyunkyu,Kim, Donggeon,Son, Eunju,Shin, Sunhwa,Sa, Jason K.,Kim, Seok-Hyung,Yoon, Yeup,Nam, Do-Hyun Elsevier 2017 Biochemical and biophysical research communication Vol.494 No.1

<P><B>Abstract</B></P> <P>The receptor tyrosine kinase c-Met plays critical roles in promoting tumor growth, invasion, metastasis, and angiogenesis in various types of cancer and is a promising therapeutic target. The development of a species cross-reactive therapeutic antibody could provide useful to comprehensive preclinical assessment in animal models. Towards this goal, we developed human/mouse cross-reactive c-Met antibodies using an antibody phage library. IRCR201, a c-Met antibody with species cross-reactivity, successfully inhibited the HGF/c-Met signaling pathway via degradation of c-Met and disruption of the binding with its partners, and demonstrated strong <I>in vivo</I> antitumor activity. In pharmacokinetic analysis, IRCR201 exhibited a nonlinear pharmacokinetic profile and showed rapid serum clearance at low dosage. <I>Ex vivo</I> fluorescence imaging and immunohistochemistry demonstrated strong tumor accumulation of IRCR201. Hepatotoxicity analysis revealed that IRCR201 does not significantly affect primary human and mouse hepatocytes. Serum chemistry analysis demonstrated that the alanine aminotransferase serum level was elevated in mice treated with 30 mg/kg IRCR201 than in PBS-treated mice, whereas the levels of aspartate aminotransferase and blood urea nitrogen did not significantly differ. Thus, IRCR201 is a potent therapeutic antibody that can disrupt the HGF/c-Met signaling axis and its species cross-reactivity would enable to evaluate precise biological activity in animal models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a novel human and mouse cross-reactive antibody, IRCR201. </LI> <LI> IRCR201 inhibits HGF/c-Met pathway through c-Met degradation. </LI> <LI> IRCR201 interferes with crosstalk between c-Met and other RTKs. </LI> <LI> IRCR201 is highly tumor-specific and has a stable pharmacokinetic profile. </LI> <LI> IRCR201 provides exceptional anti-tumoral activity in a GBM xenograft model. </LI> </UL> </P>

Task-Induced Involvement Load in Korean EFL Adult Learners` Incidental Vocabulary Learning

( Hyunkyu Park ) 글로벌영어교육학회(구 호남영어교육학회) 2017 Studies in English education Vol.22 No.3

The purpose of this study is to testify the Involvement Load Hypothesis (Hulstijn & Laufer, 2001) especially focusing on Korean adult learners. A total of 55 adult learners of two proficiency levels completed one of the three vocabulary tasks which are different in terms of involvement load index established by Hulstijn and Laufer (2001): reading comprehension (1), gap-filling (2) and unscrambling sentences (3). To measure the effectiveness of different task-induced involvement, a pre-test was administered to check both the participants` pre-knowledge regarding the 10 target words and to prove homogeneity of three assigned subgroups. Then, two post-tests were implemented, one immediately after the treatment and one two weeks after, to measure their short-term learning and long-term retention on the target words. For the adult learners, the difference of involvement load was a significant factor in short-term learning, whereas it was partially supported for long-term retention, because Task 2 was more influential than Task 3. Therefore, the present study suggests that a more effective task should be considered for adult learners in both low and high English proficiencies, who have different amount of time to prepare tests or study English, in teaching environments.

담헌(湛軒) 홍대용(洪大容) 화상(畵像)의 종류와 정본 선정에 관한 고찰

박현규 ( Park Hyunkyu ) 한국실학학회 2017 한국실학연구 Vol.0 No.33

본 논문은 향후 홍대용 화상의 정본을 정하기 위해 화상의 제작 과정과 전래, 현존본 상황과 특징에 대해 조사 분석한 것이다. 1766년(영조 42)에 조선 홍대용과 청 엄성은 북경에서 우연히 만나 흉금을 터고 학문과 세상사에 대해 필담을 나누며 천애지기로 삼았다. 이들은 헤어진 후각자 고향 집으로 돌아가 장문의 서찰을 주고받으며 우애를 쌓아갔다. 그러나 1년여 만에 엄성이 급작스럽게 죽으면서 생전의 교류는 중단되었지만, 이들이 남긴 진솔한 우정은 책자로 기술되어 세상에 널리 전해졌다. 엄성 사후에 주문조의 의해 북경 모임을 담아 『일하제금집』을 편찬되었는데, 여기에 홍대용 화상이 들어가 있다. 1766년(건륭 31) 고향으로 돌아간 엄성은 홍대용을 그리워하여 화상을 그리고 화상찬을 제했다. 엄성은 홍대용을 고결한 선비라는 뜻에서 `高士`를 화제를 삼고, 홍대용이 얼굴에 온화한 빛을 띠고 공손한 모습으로 두 손을 모아 소매 속으로 집어넣고 무릎을 구부려 마루에 대고 꿇어앉아 있는 장면을 포착해서 화상구도로 삼았다. 홍대용 화상은 병술년(1766) 엄성 원본, 정해년(1767) 모사본 계통, 경인년(1770) 재모사본 계통으로 나뉜다. 현존 홍대용 화상은 북경대학장본, 중국 국가도서관장본, 서울대학장본, 하버드대 옌칭도서관장본, 국사편찬위원회장 사진판, 북한 인민대학습당 사진판 등총 6부이다. 현존 홍대용화상은 모두 엄성 원본에서 출발했지만, 아쉽게도 나중에 거듭 모사된 것들이다. 향후 홍대용 화상의 정본을 만들 때 엄성 원본을 한번 모사한 정해년(1767) 모사본 계통의 북경대학장본과 제작년도가 가장 빠른 경인년(1770) 재모사본인 국사편찬위원회장 사진판을 기본 텍스트로 삼는다. I in this paper studied and analyzed the production process, the introduction, the condition of extant edition, and its characteristics of Hong Daeyong`s portrait to decide the original copy of the portrait hereafter. In 1766(the 42<sup>nd</sup> year of Yeongjo`s reign), Hong Daeyong of Joseon and Yan Cheng(嚴誠) of Qing met by chance in Beijing and became close friend as they spoke their bosom freely by writing about the worldly affairs. After parting and going home they developed their friendship through long letter exchange. However, their exchange during their lifetime had to stop because of Yan`s sudden death after a year of parting, their true friendship was well known to the world as their story came to be described in a book. Rixia tijin ji(日下題襟 集) was compiled after Yan`s death by Zhu Wenzao(朱文藻) who told the story of the two men`s meeting in Beijing and Hong Daeyong`s portrait was included in the book. In 1766(the 31^st year of Qianlong reign), after returned to hometown Yan Cheng who missed Hong Daeyong drew the portrait of Hong Daeyong and composed a writing on the portrait. Yan Cheng took `gaoshi` as the title of the picture because Yan considered Hong as an elegant scholar. The editions of Hong`s portrait are divided into threee lines as that of Yan Cheng`s manuscript in 1766(the 31^st year of Qianlong`s reign), the copied text made in the year of Jeonghae, 1767(the 32<sup>nd</sup> year of Qianlong`s reign), and the recopied one in the year of Gyeongin, 1770(the 35^th year of Qianlong reign). The extant portraits of Hong Daeyong are housed in Beijing University, National Library of China, Seoul National University, Yenching Library, Harvard University. Photograph versions of Hong`s portrait are housed in National Institute of Korean History and The Grand People`s Study House of North Korea. However, all of the extant portraits of Hong are origined from Yan`s original copy, these are that of copied several times later.

회복탄력성을 고려한 기상 시나리오별 가뭄 용수 공급방안: 나주호를 중심으로

박진현 ( Park Jinhyun ),고재한 ( Go Jeahan ),조영준 ( Jo Youngjun ),정경훈 ( Jung Kyunghun ),성무홍 ( Sung Muhong ),정형모 ( Jung Hyoungmo ),박현규 ( Park Hyunkyu ),유승환 ( Yoo Seunghwan ),윤광식 ( Yoon Kwangsik ) 한국농공학회 2018 한국농공학회논문집 Vol.60 No.5

Resilience has been widely used in various fields including design and operation of infrastructures. The resilient infrastructures not only reduce the damage scale of various disasters but also reduce the time and cost required for restoration. However, resilience rarely applied to promote efficient management of agricultural infrastructures. Recently, drought is an aggravating disaster by climate change and need countermeasures. Therefore, we tried to demonstrate evaluating measures in case of drought under consideration of resilience. This study applied the robustness-cost index (RCI) to evaluate alternative solution of the supply problem of a large agricultural reservoir under drought conditions. Four structural alternatives were selected to estimate the robustness index (RI) and the cost index (CI) to obtain the RCI values. Structural alternatives are classified into temporary measures and permanent measures. Temporary measures include the development of a tube wells and the installation of the portable pump, while the permanent measures include the installation of a pumping stations and the pumping water to the reservoir (Yeongsan River-Naju reservoir). RCI values were higher in permanent measures than those of temporary measures. Initial storage of the reservoir also affected RCI values of the drought measures. Permanent measures installation and management of early stage of the reservoir storage shortage was identified as the most resilient system.

비트가 소실된 데이터의 복구 및 인코딩 판별 알고리즘 개발

박현규(Hyunkyu Park),이서진(Seojin Lee),배준우(Junwoo Bae),박희진(Heejin Park) 한국정보과학회 2016 한국정보과학회 학술발표논문집 Vol.2016 No.12

조선 우인이 제공한 청 섭지선(葉志詵)의 시첩(詩帖)과 김석문(金石文) 고찰

朴現圭 ( Park Hyunkyu ) 중국어문연구회 2020 中國語文論叢 Vol.0 No.102

This study intensively analyzed the literature that Ye Zhishen(葉志詵) in Qing(淸) Dynasty was given by Joseon(朝鮮) friends and his utilization of the literature. There was a mysterious spring named the Ziwuquan(子午泉), where clear water comes out only at from 23 to 01 o’clock and from 11 to 13 o’clock, located at Pingan guan(平安館) in Beijing(北京) where three generations of the Ye(葉) family had resided. As a request from Ye Zhishen, Lee Jowon(李肇源) asked Joseon acquaintances to compose poems about the Ziwuquan and published Ziwuquan shitie(Ziwuquan poems; ≪子午泉詩帖)≫ with the poems. Ye Zhishen obtained the Epigraphy Collection of Korea directly from the Joseon friends who came in Beijing(Yanjing; 燕京) and borrowed different the Epigraphy Collection of Korea from his acquaintances of which they obtained from other Joseon friends, and thoroughly examined those Epigraphy Collection of Korea. Afterwards, he published Golyeo bi jeonmun(Gaoli bei Quanwen; ≪高麗碑全文)≫, which consisted of 4 volumes in total and contained 58 titles of the Epigraphy Collection of Korea from Shilla(新羅) to the early Joseon(朝鮮前期). The Tagohi(≪多胡碑)≫) is one of major three old stones in Japan. Seong Daejung(成大中), who was a literary official of Joseon, obtained the Tagohi Inscription from Hirai Keikei(平鱗景瑞) of Japan and afterwards, officials of Joseon imitated it in the double outer shape method and gave it to officials of Qing Dynasty. Ye Zhishen imitated to investigate the Tagohi again using the double outer shape(雙鉤) from friends of Joseon to Weng Banggang(翁方綱) and another one from Kim Jeonghui(金正喜), thereafter he published Riben canbei shuanggou ben(Japanese broken monument; ≪日本殘碑雙鉤本≫).

임진왜란 양주 蟹踰嶺전투 勝將 申恪의 참형 기록 고찰

朴現圭(PARK, HYUNKYU) 동아인문학회 2022 동아인문학 Vol.58 No.-

본 논고는 임진왜란 때 양주 蟹踰嶺전투에서 申恪이 승전을 거둔 장수임에도 불구하고 참형을 당한 기록을 찾아 고찰하는 데 중점을 두었다. 양주 해유령전투는 임진왜란 발발 이후 계속 패전을 거듭해온 조선군이 육지에서 거둔 최초로 승전이었다. 이번 승전은 조선군도 일본군과 맞서 싸워도 이길 수 있다는 투지력과 사기를 높여주는 계기가 되었다. 신각은 양주 해유령전투에서 승전을 거둔 장수였지만, 조정의 그릇된 판단으로 억울한 죽임을 당한 비운의 장수였다. 앞서 한강 방어 실패한 도원수 김명원은 자신의 잘못을 신각에게 전가시키고자 신각을 명령 불복종이라는 죄목으로 엮어 장계를 올렸다. 조정에서는 일본군과 맞서 싸워야 하는 절박한 심정과 승전을 얻고자 하는 조급증으로 김명원의 말에 따라 처형하였다. 신각의 참형은 당대의 여러 인사가 억울하다는 말을 남겼고, 후대에도 여러 문헌에 계속 거론될 정도로 널리 퍼졌다. 오늘날 양주 해유령에 해유령전적비와 신각 등을 추모하는 충현사가 세워졌다. 앞으로도 우리들은 선현들이 세운 양주 해유령전투를 새롭게 조명하고, 다시는 이처럼 억울한 일이 발생하지 않도록 역사적 반성을 할 필요가 있다. This study focuses on considering the overall military activities of Sin Gak(申恪) that has led to a victory in the Battle of Yangju Haeyulyeong (楊州蟹踰嶺) during the Imjin War(Japanese Invasion, 1592~1598; 壬辰 倭亂). The Battle of Yangju Haeyulyeong was the very first victory of the Joseon troops, which had been defeated repetitively since the outbreak of the Imjin War in 1592. This victory became a trigger to increase the fighting spirit and confidence that Joseon troops can also defeat the Japanese troops. Sin Gak was an unfortunate commander who was falsely killed by the Royal Court due to the wrong judgment even though he won the Battle of Yangju Haeyulyeong. Kim Myung-won(金命元), who previously failed to defend the Han River(漢江), placed a false report under the charge of disobedience in order to pass on his own fault to Sin Gak. And the Royal Court executed Sin Gak based on the report by Kim Myung-won, with desperate feeling to fight against the Japanese troops and impatience of victory. In the future, it is necessary for us to newly shed light on the historical implications of the Battle of Yangju Haeyulyeong as well as the sacred accomplishments of our ancestors.