• Title/Summary/Keyword: critical target

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Identification of DC21 as a Novel Target Gene Counter-regulated by IL-12 and IL-4

  • Kong, Kyoung-Ah;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.35 no.6
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    • pp.623-628
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    • 2002
  • The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

Screening of Domain-specific Target Proteins of Polo-like Kinase 1: Construction and Application of Centrosome/Kinetochore-specific Targeting Peptide

  • Ji, Jae-Hoon;Jang, Young-Joo
    • BMB Reports
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    • v.39 no.6
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    • pp.709-716
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    • 2006
  • Mammalian polo-like kinase 1 (Plk1) acts at various stages in early and late mitosis. Plk1 localizes at the centrosome and maintains this position through mitosis. Thereafter Plk1 moves to the kinetochore and midbody region, important sites during chromosome separation and cytokinesis. The catalytic domain of Plk1 is in the N-terminus region, whereas the non-catalytic region in the C-terminus of Plk1 has a conserved motif, named the Polobox. This motif is critical for Plk localization. EGFP proteins fused with the N-terminus and C-terminus of Plk1 localize in the nucleus and centrosomes, respectively. The core sequences of the polo-box (50 amino acids) also localize in Plk1 target organelles. To screen for domain-specific target proteins of Plk1, we constructed an N-terminal domain and a tandem repeat polo-box motif, and used them as templates in a yeast two-hybrid screen. The HeLa cell cDNA library indicated several proteins including the centrosome/kinetochore components or regulators, to be characterized as positive clones. Through in vitro protein binding analyses, we confirmed an interaction between these proteins and Plk1. The data reported from this study indicate that the N- and C- termini of Plk1 may function through recruitment and/or activation of domain-specific target proteins in dividing cells. Additionally, tandem repeats of the conserved core motif of the polo-box are sufficient for targeting and may be useful as a centrosome/kinetochore-specific targeting peptide.

Evaluation of Stream Water Quality to Select Target Indicators for the Management of Total Maximum Daily Loads (수질오염총량관리 대상물질 선정을 위한 하천수질 평가)

  • Park, Jun Dae;Park, Jae Hong;Oh, Seung Young;Lee, Jae Kwan
    • Journal of Korean Society on Water Environment
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    • v.29 no.5
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    • pp.630-640
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    • 2013
  • It is one of the most critical steps identifying impaired waterbodies exactly in the selection of target water quality indicators for the management of Total Maximum Daily Loads (TMDLs). Excess ratio and excess level were applied and analyzed by the stream zone basis in order to evaluate water impairment for Nakdong, Geum, Youngsan and Seomjin rivers. Each river basin was divided into stream zones in the light of its watershed and waterbody characteristics. Selected water quality parameters discussed in this study were pH, DO, BOD, COD, SS, T-P, T-Coli and F-Coli. The excess ratios of the water quality parameters were used to discriminate water bodies that did not meet water quality standards. The excess levels were used to classify the degradation of water quality. The excess ratios and the excess levels to the water quality criteria of the medium influence areas were used for each stream zone. The results indicate that the excess ratios and the excess levels are varied on the stream zone in each river basin. Three parameters, pH, DO and SS, met water quality standards in all stream zones. The other five parameters indicated very high excess ratios in most waterbodies, and especially T-P and T-Coli revealed to be very high excess levels in some waterbodies. These parameters could be considered as major target indicators for the management of TMDLs.

Evaluation of Reliability Index of Governing Load Combination for Design of Cable Supported Bridge Members (케이블교량의 부재 설계를 지배하는 하중조합에 대한 신뢰도지수 평가)

  • Paik, Inyeol;Yoon, Taeyong
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.27 no.6
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    • pp.643-651
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    • 2014
  • In this paper the reliability analyses of the cable-supported bridge design code which is recently issued in Korea are performed and the results are presented. Governing load combinations for the member design and the statistical properties of the main members are introduced and the analysis is performed using an example cable-stayed bridge for which the design is performed following the load and resistance factors defined in the design code. The reliability analysis shows the target reliability index can be achieved by applying load and resistance factors and the application of the resistance modification factor can enhance the reliability level if the importance of the bridge needs to be increased. The sensitivity analysis reveals that decreasing uncertainty of the cable strength is critical for obtaining the target reliability index. The study results show that the design using the load and resistance factors of the code can achieve the target reliability indexes for the design of cable supported bridge.

Optimization of Dose Distribution for LINAC-based Radiosurgery with Multiple Isocenters (LINAC 뇌정위적 방사선 수술시 Multiple Isocenters를 이용한 최적 선량분포 계획)

  • Suh Tae-Suk;Yoon Sei Chul;Shinn Kyung Sub;Bahk Yong Whee
    • Radiation Oncology Journal
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    • v.9 no.2
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    • pp.351-359
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    • 1991
  • The current LINAC technique for radiosurgery utilizes a single isocenter approach with multiple noncoplanar arcs. This approach results in spherical dose distributions in the target. Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. The basic approach presented in this paper is to use two or multiple isocenters with standard arcs to shape irregular target volumes through the use of multiple spherical targets. Selection of reasonable irradiation parameters in the first stage is critical to the success of real-time optimization. A useful guideline for optimum isocenter separation and collimator size is developed to shape the target margin uniformly with an desired isodose surface for an elongated target. The implementation of multiple isocenters with three dimensional dose model and application of multiple isocenters approach to several cases are discussed.

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CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer - Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects

  • Xu, Zhi-Wei;Wang, Guan-Nan;Dong, Zhou-Zhou;Li, Tao-Hong;Cao, Chao;Jin, Yu-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6685-6690
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    • 2015
  • Background: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. Materials and Methods: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. Results: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Conclusions: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.

How to Identify Critical Nodes of National Infrastructure Systems in Megacities (메가시티 국가기반체계의 핵심노드 식별 방법)

  • Sim, Jun Hak;Jang, chan Kyu;Park, Sung Jun;Kim, Ki Won;Cho, Sang Keun;Park, Sang Hyuk
    • The Journal of the Convergence on Culture Technology
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    • v.8 no.6
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    • pp.531-536
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    • 2022
  • Megacities are emerging all over the world and gradually becoming the center of an country. Therefore, Megacities are inevitably exposed to various threats such as existing, potential, supra-national, and non-military. In particular, as seen in the recent Ukraine-Russia war, national infrastructure systems has become a major target of enemies. However, considering the size of Megacities, various types of threats, and limited resources, it is impossible to completely protect all national infrastructure systems. Therefore, wisdom is necessary to identify and protect critical nodes. The critical node is the vital point to which the national infrastructure is connected. To this end, in this study, as a method for logically and systematically identifying critical nodes, Node centrality analysis method, which is a network theory, and the Center of Gravity analysis method, which is a military theory, were presented.

Interaction Between Students and Generative Artificial Intelligence in Critical Mineral Inquiry Using Chatbots (챗봇 활용 핵심광물 탐구에서 나타난 학생과 생성형 인공지능의 상호작용)

  • Sueim Chung;Jeongchan Kim;Donghee Shin
    • Journal of the Korean earth science society
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    • v.44 no.6
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    • pp.675-692
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    • 2023
  • This study used a Chatbot, a generative artificial intelligence (AI), to analyze the interaction between the Chatbot and students when exploring critical minerals from an epistemological aspect. The results, issues to be kept in mind in the teaching and learning process using AI were discussed in terms of the role of the teacher, the goals of education, and the characteristics of knowledge. For this study, we conducted a three-session science education program using a Chatbot for 19 high school students and analyzed the reports written by the students. As a result, in terms of form, the students' questions included search-type questions and non-search-type questions, and in terms of content, in addition to various questions asking about the characteristics of the target, there were also questions requiring a judgment by combining various data. In general, students had a questioning strategy that distinguished what they should aim for and what they should avoid. The Chatbot's answer had a certain form and consisted of three parts: an introduction, a body, and a conclusion. In particular, the conclusion included commentary or opinions with opinions on the content, and in this, value judgments and the nature of science were revealed. The interaction between the Chatbot and the student was clearly evident in the process in which the student organized questions in response to the Chatbot's answers. Depending on whether they were based on the answer, independent or derived questions appeared, and depending on the direction of comprehensiveness and specificity, superordinate, subordinate, or parallel questions appeared. Students also responded to the chatbot's answers with questions that included critical thinking skills. Based on these results, we discovered that there are inherent limitations between Chatbots and students, unlike general classes where teachers and students interact. In other words, there is 'limited interaction' and the teacher's role to complement this was discussed, and the goals of learning using AI and the characteristics of the knowledge they provide were also discussed.

Diagnostic Performance of Radial Probe Endobronchial Ultrasound without a Guide-Sheath and the Feasibility of Molecular Analysis

  • Moon, Seong Mi;Choe, Junsu;Jeong, Byeong-Ho;Um, Sang-Won;Kim, Hojoong;Kwon, O Jung;Lee, Kyungjong
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.4
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    • pp.319-327
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    • 2019
  • Background: Radial probe endobronchial ultrasound (R-EBUS), is effective for tissue diagnosis of lung lesions. We evaluated the diagnostic performance of R-EBUS both a guide-sheath and fluoroscopy and identified factors associated with accurate diagnosis. The feasibility of molecular and genetic testing, using specimens obtained by R-EBUS, was also investigated. Methods: The study retrospectively reviewed 211 patients undergoing R-EBUS without a guide-sheath and fluoroscopy, June 2016-May 2017. After excluding 27 patients of which the target lesion was not reached, 184 were finally included. Multivariate logistic regression was used, to identify factors associated with accurate diagnosis. Results: Among 184 patients, R-EBUS-guided biopsy diagnosed malignancy in 109 patients (59%). The remaining 75 patients (41%) with non-malignant results underwent additional work-ups, and 34 were diagnosed with malignancy. Based on final diagnosis, diagnostic accuracy was 80% (136/170), and sensitivity and specificity for malignancy were 76% (109/143) and 100% (27/27), respectively. In multivariate analysis, peripheral location (adjusted odds ratio [aOR], 3.925; 95% confidence interval [CI], 1.203-12.811; p=0.023), and central position of the probe (aOR, 2.435; 95% CI, 1.424-7.013; p=0.035), were associated with accurate diagnosis of malignancy. Molecular and genetic analyses were successful, in all but one case, with inadequate specimens. Conclusion: R-EBUS-guided biopsy without equipment, is effective for tissue diagnosis. Peripheral location and central position of the radial probe, were crucial for accurate diagnosis. Performance of molecular and genetic testing, using samples obtained by R-EBUS, was satisfactory.

Korean Learners' Interpretation of English Locative PPs with Manner of Motion Verbs

  • Kim, Jung-Tae
    • English Language & Literature Teaching
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    • v.16 no.1
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    • pp.41-59
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    • 2009
  • The present study investigated Korean learners' knowledge on the range of possible interpretations of English locative PPs with manner of motion verbs, and considers whether learners can arrive at a superset L2 grammar on the basis of positive L2 input. Unlike Korean, some English locative PPs occurring with manner of motion verbs (such as in John jumped on the bed) are ambiguous as they can be interpreted as either directional or locational. Thirty Korean learners of English in three distinct groups (Advanced EFL-only group; Intermediate-EFL-only group; and ESL-experienced group) participated in an experimental study, along with a control group of nine native speakers of English. The results of the study showed that I) Korean learners, overall, tended to interpret English locative PPs as only locational, failing to recognize the ambiguity between the directional and locational readings in the target structure; 2) For the learners who experienced only the EFL context, even highly proficient learners, as well as intermediate level learners, failed to acknowledge the ambiguity; 3) The learners who experienced the ESL context for an extended period of time could identify the target reading to some extent, although they still could not reach the native-like competence. From these results, it is argued that robustness of positive evidence, not simply its availability, is critical in the acquisition of the superset L2 targets like the present one.

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