• Molecules and Cells
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• 제21권2호
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• pp.251-260
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• 2006

During mitosis, genomic integrity is maintained by the proper coordination of anaphase entry and mitotic exit via mitotic checkpoints. In budding yeast, mitotic exit is controlled by a regulatory cascade called the mitotic exit network (MEN). The MEN is regulated by a small GTPase, Tem1p, which in turn is controlled by a two-component GAP, Bfa1p-Bub2p. Recent results suggested that phosphorylation of Bfa1p by the polorelated kinase Cdc5p is also required for triggering mitotic exit, since it decreases the GAP activity of Bfa1p-Bub2p. However, the dispensability of GEF Lte1p for mitotic exit has raised questions about regulation of the MEN by the GTPase activity of Tem1p. We isolated a Bfa1p mutant, $Bfa1p^{E438K}$, whose overexpression only partially induced anaphase arrest. The molecular and biochemical functions of $Bfa1p^{E438K}$ are similar to those of wild type Bfa1p, except for decreased GAP activity. Interestingly, in $BFA1^{E438K}$ cells, the MEN could be regulated with nearly wild type kinetics at physiological temperature, as well as in response to various checkpoint-activating signals, but the cells were more sensitive to spindle damage than wild type. These results suggest that the GAP activity of Bfa1p-Bub2p is responsible for the mitotic arrest caused by spindle damage and Bfa1p overproduction. In addition, the viability of cdc5-2 ${\Delta}bfa1 $ cells was not reduced by $BFA1^{E438K}$, suggesting that Cdc5p also regulates Bfa1p to activate mitotic exit by other mechanism(s), besides phosphorylation.

• 한국도로학회논문집
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• 제18권1호
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• pp.1-11
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• 2016

PURPOSES : This study estimated the load effect of a single heavy truck to develop a live load model for the design and assessment of bridges located on an expressway with a limited truck entry weight. METHODS : The statistical estimation methods for the live load effect acting on a bridge by a heavy vehicle are reviewed, and applications using the actual measurement data for trucks traveling on an expressway are presented. The weight estimation of a single vehicle and its effect on a bridge are fundamental elements in the construction of a live load model. Two statistical estimation methods for the application of extrapolation in a probabilistic study and an additional estimation method that adopts the extreme value theory are reviewed. RESULTS : The proposed methods are applied to the traffic data measured on an expressway. All of the estimation methods yield similar results using the data measured when the weight limit has been relatively well observed because of the rigid enforcement of the weight regulation. On the other hand, when the estimations are made using overweight traffic data, the resulting values differ with the estimation method. CONCLUSIONS : The estimation methods based on the extreme distribution theory and the modified procedure presented in this paper can yield reasonable values for the maximum weight of a single truck, which can be applied in both the design and evaluation of a bridge on an expressway.

• Journal of Microbiology
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• 제38권4호
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• pp.239-244
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• 2000

The cats gene encodes the major catalase in Sreptomyces coelicolor, whose production increases upon H$_2$O$_2$treatment. Besides the previously identified primary promoter (catApl), a minor promoter (catAp2) was newly assigned by S1 nuclease mapping. The catAp2 transcript was observed transiently upon entry into the stationary phase in liquid culture and upon differentiation on solid plates, whereas the level of catApl transcription did not chance significantly during this growth transition. ThecatApl promoter was transcribed by the major vegetative RNA polymerase holoenzyme containing $\sigma$$\^$HrdB/, whereas the catAp2 was transcribed in vitro by the holoenzyme containing $\sigma$$\^$R/ that is activated under oxidative conditions. The cia-element regulating the H$_2$O$_2$-inducibility of catApl was identified within the 23 bp inverted repeat sequence located between -65 and -43 of the catApl promoter. We roamed this sequence HRE (H$_2$O$_2$-responsive Element). The distal half of the inverted repeat was more crucial for H$_2$O$_2$-dependent induction of the catApl transcript than the proximal half. HRE most likely serves as a binding site for the H$_2$O$_2$-responsive repressor CatR.

• 한국항해항만학회지
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• 제32권10호
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• pp.821-827
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• 2008

현재 우리나라 선박관리업의 경우 선주에게만 선원의 고용권이 있으며 선박관리회사는 선원고용권이 없는 실정이다. 그리고 선박관리업자간 협력사업이 해외 선박관리업자에게는 허용되나 국내 선박관리업자 간에는 허용되지 않고 있다. 향후 해외 전문선박관리회사가 국내시장에 진출 시 국내 선박관리회사들의 경쟁력이 약화될 우려가 있다. 따라서 국내 선박관리업이 국제 경쟁력을 갖추기 위해 선원고용권 문제를 포함한 선박관리 관련 법, 제도의 미비점을 개선하고 정비하여야 할 필요성이 강조되고 있다. 본 연구는 국내 선박관리업의 선원관리제도 관점에서 국내 선박관리업의 활성화 방안을 검토하였다. 선원인력양성 선원의 고용권 보장, 선박관리회사간 재계약 허용, 비정규직 보호법에서 선원은 제외 등을 발전 방안으로 제시하였다.

• 한국컴퓨터게임학회논문지
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• 제31권4호
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• pp.145-155
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• 2018

본 연구는 게임 관련 전문가 23명에게 델파이 기법을 사용해 기존의 게임 가치평가에 추가적 요소들을 추출해 보고자 한다. 기존에 제시된 게임 컨텐츠의 평가 모델을 이용하여 개발 모델의 특성을 전반적으로 검토 한 결과, 컨텐츠를 선정 할 때 가치 평가 요소가 선정되었음을 알 수 있었으며 델파이 분석은 2차에 걸쳐서 이루어졌으며, 1차는 전문가 FGI, 2차는 델파이 설문으로 진행되었다. 결과, 기술 이전 및 보급, 상용화 촉진을 위한 세부 내용 등 관련 항목등에서 보다 세밀한 요소들이 제시되었다. 포커스 그룹 인터뷰를 통해 추가 요인을 추출하고 게임 업계의 컨텐츠 성공에 대한 시장 분석을 통해 시장 규모, 성장 잠재력, 규제 및 시장 매력과 위험을 예측 했으며 이를 통해 관련업계는 성공 목표에 대한 시장 분석을 통해 시장 규모, 성장 잠재력, 규제, 시장 호소력 및 위험성을 이해할 수 있을 것으로 기대한다. 이 연구는 제안 된 평가 요소가 게임 및 문화 콘텐츠 산업 전체에 적용될 수 있음을 시사하며 또한 콘텐츠의 시장 가치 평가, 목적 및 목표 설정, 진입 방법 선택, 전략 요소 등 시장 요인을 구성하는 것에 도움이 될 것이다.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.302-310
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• 2019

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

• International Journal of Oral Biology
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• 제46권4호
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• Journal of Periodontal and Implant Science
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• 제47권2호
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• pp.116-131
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• 2017

Purpose: The entry of bacteria or harmful substances through the epithelial seal of human gingival keratinocytes (HGKs) in the junctional epithelium (JE) is blocked by specialized intercellular junctions such as E-cadherin junctions (ECJs). However, the influence of roughened substrates, which may occur due to apical migration of the JE, root planing, or peri-implantitis, on the development of the ECJs of HGKs remains largely unknown. Methods: HGKs were cultured on substrates with varying levels of roughness, which were prepared by rubbing hydrophobic polystyrene dishes with silicon carbide papers. The activity of c-Jun N-terminal kinase (JNK) was inhibited with SP600125 or by transfection with JNK short hairpin RNA. The development of intercellular junctions was analyzed using scanning electron microscopy or confocal laser scanning microscopy after immunohistochemical staining of the cells for E-cadherin. The expression level of phospho-JNK was assessed by immunoblotting. Results: HGKs developed tight intercellular junctions devoid of wide intercellular gaps on smooth substrates and on rough substrates with low-nanometer dimensions (average roughness $[Ra]=121.3{\pm}13.4nm$), although the ECJs of HGKs on rough substrates with low-nanometer dimensions developed later than those of HGKs on smooth substrates. In contrast, HGKs developed short intercellular junctions with wide intercellular gaps on rough substrates with mid- or high-nanometer dimensions ($Ra=505.3{\pm}115.3nm$, $867.0{\pm}168.6nm$). Notably, the stability of the ECJs was low on the rough substrates, as demonstrated by the rapid destruction of the cell junction following calcium depletion. Inhibition of JNK activity promoted ECJ development in HGKs. JNK was closely associated with cortical actin in the regulation of ECJs in HGKs. Conclusions: These results indicate that on rough substrates with nanometer dimensions, the ECJs of HGKs develop slowly or defectively, and that this effect can be reversed by inhibiting JNK.

• 유통과학연구
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• 제13권2호
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• pp.95-104
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• 2015

Purpose - This is a comparative study of the market development and characteristics of Ulsan in South Korea, Fukuoka in Japan, and Yanji in China, which are major East Sea Rim cities with adjacent areas of similar natural characteristics of the sea and the country. Particularly, it considers these aspects while focusing on the evolution of networks that appear in the distribution system and at the same time examining the institutions of market activation and regulations that are handled by the central and the local government and the changing logistics due to the development of transportation and the concern of food safety, using a meso-analysis approach. Research design, data, and methodology - The study used a historical and comparative approach with a focus on case studies. It made use of various materials such as local newspaper articles, reports, literature, interviews with experts, discussions with local merchants, discussions with customers, and so forth. Results - In the case of Fukuoka, from the 1960s, due to the entry of supermarkets, supermarkets expanded and they have now come to a dominant market position in the current market. They offer a convenient and comfortable environment while providing a large mall offering a variety of educational and cultural activities for customers to meet the customers' needs, such as the preferences of Korean tourists, who appear to prefer Japanese foods. The Fukuoka City Central Wholesale Market has been exporting fruits and vegetables as well as seafood products to Korea, China, and so forth. In the case of Ulsan, as in the early 2000s, due to the expansion of supermarkets, the traditional markets have been shrinking and further, the modernization of traditional markets was conducted under the auspices of the Small Business Administration. In addition to the large discount malls, the expansion of SSM is expected to further drive the small trader bay. Shopping malls, department stores, and traditional markets contend with each other in Yanji, China, but a large number of citizens appear to prefer traditional markets and imported milk in the supermarket after the melamine scandal in China. Recently, the WanYuan (萬源) wholesale market has been partially completed and made an attempt to become a logistics hub in Northeast Asia. Conclusions - For the development of Korea's retail industry, it is important to offer the government with proposals regarding desired regulation. On the other hand, in order to enable the business of traditional markets, it requires an association for cultural tourism. At present, it would be better to provide a venture fund for the youth rather than infrastructure support. This study emphasizes the importance of institutions and policy to develop networks in the East Sea Rim. Future studies should conduct a survey on customers, managers, and merchants more carefully and systematically to understand the market situation while considering the size of the city and its evolution of markets, as well as policies and institutions.

• Nutrition Research and Practice
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• 제9권2호
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• pp.129-136
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• 2015

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.