• 제목/요약/키워드: Action Target 3

검색결과 222건 처리시간 0.029초

Comparison of flood inundation simulation between one- and two-dimensional numerical models for an emergency action plan of agricultural reservoirs

  • Kim, Jae Young;Jung, Sung Ho;Yeon, Min Ho;Lee, Gi Ha;Lee, Dae Eop
    • 농업과학연구
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    • 제48권3호
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    • pp.515-526
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    • 2021
  • The frequency of typhoons and torrential rainfalls has increased due to climate change, and the concurrent risk of breakage of dams and reservoirs has increased due to structural aging. To cope with the risk of dam breakage, a more accurate emergency action plan (EAP) must be established, and more advanced technology must be developed for the prediction of flooding. Hence, the present study proposes a method for establishing a more effective EAP by performing flood and inundation analyses using one- and two-dimensional models. The probable maximum flood (PMF) under the condition of probable maximum precipitation (PMP) was calculated for the target area, namely the Gyeong-cheon reservoir watershed. The breakage scenario of the Gyeong-cheon reservoir was then built up, and breakage simulations were conducted using the dam-break flood forecasting (DAMBRK) model. The results of the outflow analysis at the main locations were used as the basis for the one-dimensional (1D) and two-dimensional (2D) flood inundation analyses using the watershed modeling system (WMS) and the FLUvial Modeling ENgine (FLUMEN), respectively. The maximum inundation area between the Daehari-cheon confluence and the Naeseong-cheon location was compared for each model. The 1D flood inundation analysis gave an area of 21.3 km2, and the 2D flood inundation analysis gave an area of 21.9 km2. Although these results indicate an insignificant difference of 0.6 km2 in the inundation area between the two models, it should be noted that one of the main locations (namely, the Yonggung-myeon Administrative and Welfare Center) was not inundated in the 1D (WMS) model but inundated in the 2D (FLUMEN) model.

네트워크 약리학 분석을 통한 사군자탕(四君子湯)의 뇌경색 억제 기전 예측 (Prediction of cerebral infarction suppression mechanism of the Sagunja-Tang through network pharmacology analysis)

  • 임지연;이병호;조수인
    • 대한한의학방제학회지
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    • 제30권4호
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    • pp.293-304
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    • 2022
  • Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

IQGAP1, a signaling scaffold protein, as a molecular target of a small molecule inhibitor to interfere with T cell receptor-mediated integrin activation

  • Li, Lin-Ying;Nguyen, Thi Minh Nguyet;Woo, Eui Jeon;Park, Jongtae;Hwang, Inkyu
    • 농업과학연구
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    • 제47권2호
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    • pp.361-373
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    • 2020
  • Integrins such as lymphocyte function-associated antigen -1 (LFA-1) have an essential role in T cell immunity. Integrin activation, namely, the transition from the inactive conformation to the active one, takes place when an intracellular signal is generated by specific receptors such as T cell receptors (TCRs) and chemokine receptors in T cells. In an effort to explore the molecular mechanisms underlying the TCR-mediated LFA-1 activation, we had previously established a high-throughput cell-based assay and screened a chemical library deposited in the National Institute of Health in the United States. As a result, several hits had been isolated including HIKS-1 (Benzo[b]thiophene-3-carboxylic acid, 2-[3-[(2-carboxyphenyl) thio]-2,5-dioxo-1-pyrrolinyl]-4,5,6,7-tetrahydro-,3-ethyl ester). In an attempt to reveal the mode of action of HIKS-1, in this study, we did drug affinity responsive target stability (DARTS) assay finding that HIKS-1 interacted with the IQ motif containing GTPase activating protein 1 (IQGAP1), a 189 kDa multidomain scaffold protein critically involved in various signaling mechanisms. Furthermore, the cellular thermal shift assay (CETSA) provided compelling evidence that HIKS-1 also interacted with IQGAP1 in vivo. Taken together, it can be concluded that HIKS-1 interferes with the TCR-mediated LFA-1 activation by interacting with IQGAP1 and thereby disrupting the signaling pathway for LFA-1 activation.

산화적 활성화 과정을 통한 N-dimethoxyphosphinothioyl carbofuran의 독성발현 (Toxic action of N-dimethylphosphinothioyl carbofuran by oxidative activation process)

  • 양규완;이석종;김성문;한대성;허장현
    • 농약과학회지
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    • 제2권2호
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    • pp.10-15
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    • 1998
  • Carbofuran 및 N-dimethoxyphosphinothioyl carbofuran (PSC)의 AChE에 대한 이분자 저해 속도상수(bimolecular inhibition rate constant, $k_{i}$)를 관찰하였다. Carbofuran은 $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$으로 높은 저해효과를 보이고 있는 반면, PSC는 $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$으로 carbofuran에 비하여 AChE에 대한 저해력이 600배 정도 낮은 저해력을 갖고 있는 것으로 관찰되어 독성발현을 위하여 활성화 과정이 필요한 것으로 확인되었다. AChE/mixed function oxidase(mfo) coupling system을 이용한 microsomal oxidative activation 실험에서 PSC의 AChE에 대한 저해력이 control에 비하여 NADPH가 첨가된 oxidase 처리구에서 800배 더 강하게 나타났으며, cytochrome $P_{450}$의 저해제를 첨가한 oxidase+PBO 처리구에서는 control의 저해 경향과 유사하였다. 또한 생쥐 뇌 AChE에 대한 PSC의 $I_{50}$은 28 mg/kg인 반면 PBO를 전처리하였을 경우 $I_{50}$은 57 mg/kg으로 나타나 cytochrome $P_{450}$ 저해제로 인하여 PSC의 저해력이 2배정도 감소된 것을 관찰할 수 있었고, PSC는 독성발현을 위하여 활성화 과정을 거쳐야 하며, 이 과정에서 cytochrome $P_{450}$ 이 작용함을 확인할 수 있었다. PSC와 MCPBA를 반응시켜 산화 과정을 통하여 생성된 독성대사물을 분석한 결과 반응산물의 약 55%가 carbofuran임을 확인할 수 있었다. 본 연구를 통하여 PSC의 활성화 과정을 통한 독성발현에 cytochrome $P_{450}$이 중요한 역할을 하는 효소임을 확인할 수 있었고, PSC의 산화적 활성화 과정을 통한 주된 독성대사물이 carbofuran임을 확인할 수 있었다.

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Preliminary ALARA residual radioactivity levels for Kori-1 decommissioning and analysis of results and effects of remediation area

  • Seo, Hyung-Woo;Yu, Ji-Hwan;Kim, Gi-Lim;Son, Jin-Won
    • Nuclear Engineering and Technology
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    • 제54권3호
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    • pp.1136-1144
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    • 2022
  • The effects of nearby residents and the public by the residual contamination from the decommissioning of nuclear facilities should comply with the dose criteria, and whether additional remediation action is necessary from the ALARA perspective must be determined. Therefore, we analyzed the requirements of ALARA action levels and performed preliminary ALARA evaluation. The ratio of residual contamination concentration to DCGL was calculated for the basement fill and the building occupancy mode. The results showed that the additional remediation actions below DCGL are not justified. In addition, we analyzed the effect of remediation area. It was noted that the increase of the remediation area showed a positive correlation with the Conc/DCGL value in the basement fill mode. On the other hand, in the building occupancy mode, since the floor area of the building is the target of remediation and has the effect of increasing the same as the evaluation area of the building occupants, but due to the difference in the amount of increase, the Conc/DCGL showed a negative correlation. We expect the approach and method of ALARA evaluation can be utilized for concrete cost-benefit calculation during the decommissioning or at the time of remediation.

당뇨 합병증과 군령탕 구성성분의 네트워크 약리학 분석 및 효능 예측 (Network Pharmacology Analysis and Efficacy Prediction of GunryeongTang Constituents in Diabetic Complications)

  • 윤정주;김혜윰;태애림;이호섭;강대길
    • 대한한의학방제학회지
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    • 제32권1호
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    • pp.11-28
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    • 2024
  • Objectives : GunRyeong-Tang(GRT) is a traditional herbal prescription that combines Oryeongsan and Sagunja-tang. This study employed network analysis methods on the components of GRT and target genes related to diabetes complications to predict the improvement effects of GRT on diabetes complications. Methods : The collection of active compounds of GRT and related target genes involved the utilization of public databases and the PubChem database. We selected diabetes complication-related genes using GeneCards and confirmed their correlation through comparative analysis with the target genes of GRT. We constructed a network using Cytoscape 3.9.1 and conducted topological analysis. To predict the mechanism, we performed functional enrichment analysis based on Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results : Through network analysis, 234 active compounds and 1361 related genes were collected from GRT. A total of 9,136 genes related to diabetes complications were collected, and 1,039 target genes overlapping with the components of GRT were identified. The core genes of this network were TP53, INS, AKT1, ALB, and EGFR. In addition, GRT significantly reduced the H9c2 cell size and the expression of myocardial hypertrophy biomarkers (ANP, BNP), which were increased by high glucose (HG). Conclusions : Through this study, we were able to predict the activity and mechanism of action of GRT on diabetes and diabetic complications, and confirmed the potential of GRT as a treatment for diabetes complications through the effect of GRT on improving myocardial hypertrophy for diabetic cardiomyopathy.

LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p

  • Luan, Xiaotian;Wang, Yankui
    • Journal of Gynecologic Oncology
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    • 제29권6호
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    • pp.95.1-95.17
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    • 2018
  • Objective: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. Methods: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. Results: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. Conclusion: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.

Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in $Ca^{2+}$-activated $K^+$ Channels

  • Kim, Yang-Mi;Kim, Wun-Jae;Cha, Eun-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • 제15권5호
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    • pp.279-283
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    • 2011
  • Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased $BK_{Ca}$ current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration ($IC_{50}$) of quercetin was $45.5{\pm}7.2{\mu}m$. The quercetin-evoked $BK_{Ca}$ current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific $BK_{Ca}$ blocker and iberiotoxin (IBX; 100 nM) a $BK_{Ca}$-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol ($DiBAC_4$2(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect ($30.3{\pm}13.5%$) which was recovered to $53.3{\pm}10.5%$ and $72.9{\pm}3.7%$ by TEA and IBX, respectively. Taken together our results indicate that activation of $BK_{Ca}$ channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

Rabson Mendenhall syndrome의 치험 증례 (RABSON MENDENHALL SYNDROME : A CASE REPORT)

  • 권장혁;박기태
    • 대한소아치과학회지
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    • 제31권3호
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    • pp.481-485
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    • 2004
  • Rabson Mendenhall syndrome은 Rabson과 Mendenhall에 의해 1955년 처음 발표된 증후군으로서, 심한 insulin resistance를 보이는 희귀한 상염색체 열성 유전성 질환이다. Insulin receptor의 돌연변이나 insulin이 작용하는 다른 target cell의 결함에 의해 나타나며, 일반적인 증상으로는 흑색가시세포종(acanthosis nigricans), 다모증(hypertrichosis), 손발톱 비대(onychauxis), 성장 지체 (growth retardation), 성 조숙(precocious puberty), 생식기의 비대, 팽만된 복부(protuberant abdomen), 건성 피부(xerotic skin) 등이 나타난다. 악안면 영역에서는 치아의 이형성, 거친 얼굴의 피부, 하악 전돌, 균열 혀 (fissured tongue)와 같은 특징적 증상이 나타난다. 이에 본 증례에서는 Rabson Mendenhall syndrome으로 본원에 내원한 4세 환아에게 관찰된 치과적 특징들에 관하여 보고하는 바이다.

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Resource Allocation Strategy of Internet of Vehicles Using Reinforcement Learning

  • Xi, Hongqi;Sun, Huijuan
    • Journal of Information Processing Systems
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    • 제18권3호
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    • pp.443-456
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    • 2022
  • An efficient and reasonable resource allocation strategy can greatly improve the service quality of Internet of Vehicles (IoV). However, most of the current allocation methods have overestimation problem, and it is difficult to provide high-performance IoV network services. To solve this problem, this paper proposes a network resource allocation strategy based on deep learning network model DDQN. Firstly, the method implements the refined modeling of IoV model, including communication model, user layer computing model, edge layer offloading model, mobile model, etc., similar to the actual complex IoV application scenario. Then, the DDQN network model is used to calculate and solve the mathematical model of resource allocation. By decoupling the selection of target Q value action and the calculation of target Q value, the phenomenon of overestimation is avoided. It can provide higher-quality network services and ensure superior computing and processing performance in actual complex scenarios. Finally, simulation results show that the proposed method can maintain the network delay within 65 ms and show excellent network performance in high concurrency and complex scenes with task data volume of 500 kbits.