• Title/Summary/Keyword: PPi

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Computational Identification of Essential Enzymes as Potential Drug Targets in Shigella flexneri Pathogenesis Using Metabolic Pathway Analysis and Epitope Mapping

  • Narad, Priyanka;Himanshu, Himanshu;Bansal, Hina
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.621-629
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    • 2021
  • Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen's essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

Pharmacological Treatment for Peptic Ulcer Bleeding (소화성 궤양 출혈의 약물 치료)

  • Ma, Dae Won;Kim, Byung-Wook
    • The Korean journal of helicobacter and upper gastrointestinal research
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    • v.18 no.4
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    • pp.231-234
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    • 2018
  • Peptic ulcer bleeding (PUB) is the most common cause of non-variceal upper gastrointestinal bleeding, and its frequency has been declining over the past decades. However, mortality from PUB persists, and it is still a serious challenge in clinical practice. Although endoscopic intervention is the basic treatment modality for PUB, pharmacological therapy is an important adjunct. The emergence of proton pump inhibitors (PPIs) enables maintenance of intragastric pH >6, which greatly helps in the treatment of PUB. Continuous intravenous infusion of high-dose PPI reduces the re-bleeding rate, thereby helping avoid additional surgery in patients with high-risk stigmata. Moreover, administration of PPIs prior to endoscopy may reduce the need for additional endoscopic intervention. Recently introduced gastric acid suppressants, such as potassium-competitive acid blockers, have shown promising results in further treatment of PUB.

Assessment of Radar Precipitation Applicability for Watershed Area Precipitation Estimation (유역 면적강수량 산정을 위한 레이더 강수량 활용성 평가)

  • Kim, Tae-Jeong;Song, Jae-Hyun;Lee, Sung-Ho;Lee, Chung-Dea
    • Proceedings of the Korea Water Resources Association Conference
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    • 2022.05a
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    • pp.441-441
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    • 2022
  • 국내외적으로 정확한 수문기상 현상의 관측에 대한 수요가 증가하고 있다. 이를 위하여 기존의 재래식 관측장비의 한계성을 극복하고자 첨단장비가 활발하게 도입되고 있다. 우리나라는 관악산 기상레이더를 시작으로 하천 및 도심지의 돌발홍수 정보를 제공하고자 강우레이더 신설을 진행하고 있다. 본 연구에서는 하천유역조사 사업에서 티센다각형법을 이용하여 유역단위 면적평균강수량을 산정하는 경우 영동권역과 같이 지상관측소 밀집도 부족으로 인하여 발생하는 강수량의 공간적 편차를 정량적으로 검토하고자 전국 하천유역에 대하여 1.5km Constant Altitude PPI(CAPPI) 합성장의 레이더 강수량을 활용한 유역단위 면적평균강수량을 산정하고 지상 강수량과 통계적 적합도(goodness of fit)를 평가하였다. 지상 강수량을 활용한 유역단위 면적평균강수량과 레이더 강수량은 높은 상관성을 나타내었으나 관측기법의 특성으로 발생하는 정량적 편의(bias) 보정의 필요성을 확인하였다. 시공간적으로 고해상도의 레이더 강수정보를 활용하기 위하여 활용 목적에 적합한 레이더 강수량 보정기법의 개발이 필요할 것으로 사료된다. 또한, 대용량 레이더 자료를 안정적으로 처리할 수 있는 플랫폼 및 레이더 강수량 품질관리 체계 구축을 통하여 수문조사 및 수문해석 지원이 가능할 것으로 판단된다.

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A Study of DRMs in IPTV and Contents Sharing between different DRMs (IPTV기반 DRM 구현 및 이종 DRM간 상호 연동 방안에 관한 연구)

  • Jung, Jong-Jin;Lim, Tae-Beom;Lee, Seok-Pil
    • Proceedings of the Korea Information Processing Society Conference
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    • 2011.04a
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    • pp.692-695
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    • 2011
  • 미디어 서비스 및 디스커버리 관련 기술 개발은 주로 DTV, 인터넷, 개인 모바일 멀티 미디어 기기 중심의 미디어 서비스가 주를 이루고, 이러한 미디어 서비스들은 홈 네트워크 환경과 융합하여 홈 미디어 서비스의 새로운 서비스를 창출하고 있다. 개인들은 이미 많은 이동형 멀티미디어 기기들을 소유하기 시작했고, 각 기기마다 플레이 가능한 컨텐츠 포맷, 라이선스 구조, 상세정보를 기술하는 정보들이 서로 상이하게 제공되기도 한다. 이런 멀티디미어 환경의 발달과 함께, 개인간 또는 개인이 소유한 기기간 컨텐츠를 공유하고자 하는 요구가 생겨나고, 개인 맞춤을 위한 서비스를 받고자 소유한 개인 컨텐츠 포맷 및 라이선스 파일들 개인정보와 콘텐츠를 기술하는 메타 데이터들은 DRM 정보, 개인의 습성 및 취향 등에 대한 개인 정보를 포함하고 있어 보안 및 보호가 필요하다. 따라서 IPTV 환경에서 이종 DRM이 설치된 기기사이에 컨텐츠 상호 연동 방에 대한 연구를 하였다.

High performance Algorithm for extracting and redicting MAP Kinase signaling pathways based on S. cerevisiae rotein-Protein Interaction and Protein location Information (S. cerevisiae 단백질간 상호작용과 세포 내 위치 정보를 활용한 MAP Kinase 신호전달경로추출 및 예측을 위한 고성능 알고리즘 연구)

  • Jo, Mi-Kyung;Kim, Min-Kyung;Park, Hyun-Seok
    • Journal of the Korea Society of Computer and Information
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    • v.14 no.3
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    • pp.193-207
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    • 2009
  • Intracellular signal transduction is achieved by protein-protein interaction. In this paper, we suggest high performance algorithm based on Yeast protein-protein interaction and protein location information. We compare if pathways predicted with high valued weights indicate similar tendency with pathways provided in KEGG. Furthermore, we suggest extracted results, which can imply a discovery of new signaling pathways that is yet proven through experiments. This will be a good basis for research to discover new protein signaling pathways and unknown functions of established proteins.

Development of web-based system for miRNA and mRNA integrated analysis (miRNA 와 mRNA 통합 분석을 위한 웹 기반 시스템 개발)

  • Kim, Da-Yeon;Ko, Younhee
    • Proceedings of the Korea Information Processing Society Conference
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    • 2022.11a
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    • pp.690-692
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    • 2022
  • 기존의 질병 관련 연구들은 대부분 유의미하게 변화되는 유전자들을 찾아내고(Differentially Expressed Genes, DEGs), 이들이 연관된 생물학적 패스웨이(biological pathway)를 찾아내는 방향으로 이루어졌다. 더불어 miRNA(microRNA)가 많은 mRNA 의 발현을 조절하며, 실제 면역, 대사 및 세포 사멸을 포함한 여러 필수 생리학적 및 질병에 매우 중요한 역할을 한다고 밝혀지며, 바이오 마커로써의 miRNA 를 찾아내고자 하는 연구가 활발히 진행되기 시작하였다. 하지만 mRNA 나 miRNA 의 독립적인 연구만으로는 명확한 질병과의 연관성이나 기능을 이해하기에는 어려움이 있다. 따라서 본 연구에서는 질병 상태에서 유의미하게 변화되는 miRNA 와 이러한 miRNA 에 의해 조절되는 mRNA 를 함께 고려하여 분석함으로써, 실제 질병의 발병 원인이 되는 생물학적 패스웨이나 메커니즘을 밝히고자 하였다. 또한, miRNA 와 mRNA 의 연관성을 찾기 위해, PPI(protein-protein interaction) 네트워크에 기반을 둔 RWR(Random Walk with Restart Algorithm)를 적용하여, 직접적 연관성뿐 아니라, 유전자 간의 숨겨진 간접적인 패스웨이를 고려하여 분석하기 위한 웹 기반 시스템을 개발하였다. 이 시스템은 mRNA-miRNA 를 함께 고려한 통합 분석을 통해 숨겨진 질병의 메커니즘을 이해하고 치료 방법을 찾아내는 데 크게 공헌할 것이다.

A Novel Approach to Investigating Protein/Protein Interactions and Their Functions by TAP-Tagged Yeast Strains and its Application to Examine Yeast Transcription Machinery

  • Jung, Jun-Ho;Ahn, Yeh-Jin;Kang, Lin-Woo
    • Journal of Microbiology and Biotechnology
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    • v.18 no.4
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    • pp.631-638
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    • 2008
  • Tandem affinity purification (TAP) method combined with LC-MS/MS is the most accurate and reliable way to study the interaction of proteins or proteomics in a genome-wide scale. For the first time, we used a TAP-tag as a mutagenic tool to disrupt protein interactions at the specific site. Although lots of commonly used mutational tools exist to study functions of a gene, such as deletional mutations and site-directed mutagenesis, each method has its own demerit. To test the usefulness of a TAP-tag as a mutagenic tool, we applied a TAP-tag to RNA polymerase II, which is the key enzyme of gene expression and is controlled by hundreds of transcription factors even to transcribe a gene. Our experiment is based on the hypothesis that there will be interrupted interactions between Pol II and transcription factors owing to the TAP-tag attached at the C-terminus of each subunit of Pol II, and the abnormality caused by interrupted protein interactions can be observed by measuring a cell-cycle of each yeast strain. From ten different TAP-tagged strains, Rpb7- and Rpb12-TAP-tagged strains show severe defects in growth rate and morphology. Without a heterodimer of Rpb4/Rpb7, only the ten subunits Pol II can conduct transcription normally, and there is no previously known function of Rpb7. The observed defect of the Rpb7-TAP-tagged strain shows that Rpb7 forms a complex with other proteins or compounds and the interruption of the interaction can interfere with the normal cell cycle and morphology of the cell and nucleus. This is a novel attempt to use a TAP-tag as a proteomic tool to study protein interactions.

Student Satisfaction Study and Interrater Comparative Study on Patient-Physician Interaction Score of Clinical Performance Examination in Korean Medical Education (한의학 교육에서 진료수행평가에 대한 학생 만족도 및 환자 - 의사관계 점수의 채점자간 비교 연구)

  • Cho, Chung Sik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.29 no.2
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    • pp.152-159
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    • 2015
  • As for medical education, not only acquirement of knowledge but also practical clinical competence is important because it is needed on primary medicine. Under this trend, Clinical Performance Examination(CPX) is already being practiced in medical college. But in spite of its importance, CPX is not yet practiced in Korean medical college. So, by contemplating necessity and outcome of CPX, We try to offer basic data for future imposition and improvement of CPX in Korean medical education. 49 students of grade 3 in a Daejeon Korean Medical College were targets of investigation. After educated about CPX in advance, They treated simulated patient and answered questionnaire about CPX. Then, their treatment was scored by Professor and simulated patients. Total 49 members responded to the survey and the results of the analysis were as follows. The answer that CPX is useful(Mean=4.12) and essential for acquiring professionalism of treatment(Mean=4.02) was got high scores. But many respondents replied about necessity of better CPX environment and felt difficulty about PPI(45%). Meanwhile, Professor group(Mean=9.24) tended to give more high score than Simulated patient group(Mean=7.94). This study can be very useful for composing basic data of CPX in Korean medical College and improving practical clinical competence of students. But this study has also some limits like area, respondent selection, group module etc. So, more detailed and comprehensive survey is needed. This work was supported by the Daejeon University Research Grant.

High Affinity Pharmacological Profiling of Dual Inhibitors Targeting RET and VEGFR2 in Inhibition of Kinase and Angiogeneis Events in Medullary Thyroid Carcinoma

  • Dunna, Nageswara Rao;Kandula, Venkatesh;Girdhar, Amandeep;Pudutha, Amareshwari;Hussain, Tajamul;Bandaru, Srinivas;Nayarisseri, Anuraj
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7089-7095
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    • 2015
  • Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGNPC- 0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC.

Development of a Wave Monitoring System Using a Marine Radar (항해용 레이더를 이용한 파랑 모니터링 시스템 개발)

  • PARK JUN-SOO;PARK SEUNG-GEUN;KWON SUN-HONG;PARK GUN-IL;CHOI JAE-WOONG;KANG YUN-TAE;HA MUN-KEUN
    • Journal of Ocean Engineering and Technology
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    • v.20 no.1 s.68
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    • pp.37-42
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    • 2006
  • In the ocean engineering field, information about the ocean environment is important for planning, design, and operation, especially the wave information. High precision wave data is also important for considering environmental problems, like efficient operation of ships. For this purpose, many methods were considered in the past. However, an on-board directing wave measurement system has not been incorporated. The use of conventional marine radar Plane Position Indicator (PPI) images allows the estimation of wave information on a real-time basis, using both space and time information, regarding the evolution of ocean surface waves. In order to achieve data acquisition, the Radar Scan Converter (RSC) has been developed. Three-dimensional analysis was performed. The comparison of wave information derived from this system, and that of wave buoy, shows that this wave field detecting system can be a useful tool.