• Molecules and Cells
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• v.41 no.6
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• Journal of Technology Innovation
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• v.19 no.1
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• pp.1-27
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• 2011

This paper aims to measure and analyze R&D productivities and efficiencies of 17 major OECD countries including Korea over the 1984-2008 period by using the Malmquist Productivity Index and Data Envelopment Analysis, classifying R&D performance into an output and outcome aspects. It also searches the Korea's current status and characteristics in each R&D stage to enhance Total Factor Productivity (TFP) compared with other developed countries. Our major findings are the followings: (i) Korea's productivity index of R&D input vis-a-vis R&D output is very high (13.39% annual growth rate) compared with those of major advanced countries, whereas the annual average of efficiency index is very low (0.33), i.e. Korea's technical efficiency index has risen to 0.83 at the last time series started at 0.10 point and come up to the level of major advanced countries. (ii) the Korea's productivity index of R&D output vis-a-vis R&D outcome is very low (14.02% annual reduction rate) compared with those of major advanced countries, whereas the annual average of efficiency index is very high (0.22), i.e. Korea's integrated frontier technical efficiency index has dropped to 0.057 at the last time series started at 1.00 point and coming up to the level of major advanced countries. (iii) The productivity of R&D input vis-a-vis R&D outcome is positively correlated with that of R&D output vis-a-vis R&D outcome and the growth of R&D input factors. In a nutshell, it implicates that the effort to take advantage of R&D outputs, namely establishing the diffusion and commercialization system of technical knowledge to the level of developed countries, should be strengthened over that on the growth of R&D investment and output for enhancing R&D productivity and efficiency in Korea.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1134-1145
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• 2022

SCO6993 (606 amino acids) in Streptomyces coelicolor belongs to the large ATP-binding regulators of the LuxR family regulators having one DNA-binding motif. Our previous findings predicted that SCO6993 may suppress the production of pigmented antibiotics, actinorhodin, and undecylprodigiosin, in S. coelicolor, resulting in the characterization of its properties at the molecular level. SCO6993-disruptant, S. coelicolor ΔSCO6993 produced excess pigments in R2YE plates as early as the third day of culture and showed 9.0-fold and 1.8-fold increased production of actinorhodin and undecylprodigiosin in R2YE broth, respectively, compared with that by the wild strain and S. coelicolor ΔSCO6993/SCO6993⁺. Real-time polymerase chain reaction analysis showed that the transcription of actA and actII-ORF4 in the actinorhodin biosynthetic gene cluster and that of redD and redQ in the undecylprodigiosin biosynthetic gene cluster were significantly increased by SCO6993-disruptant. Electrophoretic mobility shift assay and DNase footprinting analysis confirmed that SCO6993 protein could bind only to the promoters of pathway-specific transcriptional activator genes, actII-ORF4 and redD, and a specific palindromic sequence is essential for SCO6993 binding. Moreover, SCO6993 bound to two palindromic sequences on its promoter region. These results indicate that SCO6993 suppresses the expression of other biosynthetic genes in the cluster by repressing the transcription of actII-ORF4 and redD and consequently negatively regulating antibiotic production.

• Genomics & Informatics
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• v.20 no.2
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• pp.20.1-20.13
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• 2022

Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.2
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• pp.153-159
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• 2007

In our previous study, overexpression of extracellular proteinase inhibitor (Expi) gene accelerated apoptosis of mammary epithelial cells, and induced expression of B cell activating factor (BAFF) gene. In this study, we found induction of BAFF-receptor (BAFF-R) gene expression in the Expi-transfected cells. A proliferation-inducing ligand (APRIL) gene is another TNF family member and the closest known relative of BAFF. We found induction of APRIL gene expression in the Expi-overexpressed apoptotic cells. NF-${\kappa}$B gene was also induced in the Expi-overexpressed cells. Expression patterns of BAFF and APRIL pathway-related genes were examined in in vivo mouse mammary gland at various reproductive stages. Expression levels of BAFF gene were very low at early pregnancy, increased from mid-pregnancy, and peaked at lactation, and thereafter decreased at involution stages of mammary gland. Expression of BAFF-R gene was highly induced in involution stages compared to lactation stages. Thus, expression patterns of BAFF-R gene were correlated to apoptotic status of mammary gland: active apoptosis of mammary epithelial cells occurs at involution stage of mammary gland. Expression levels of NF-${\kappa}$B gene were higher in involution stages compared to lactation stages. We analyzed mRNA levels of bcl-2 family genes from different stages of mammary development. Bcl-2 gene expression was relatively constant during lactation and involution stages. There was a slight increase in bcl-xL gene expression in involution stages compared to lactation state. Bax gene expression was highly induced in involution stage. Our results suggest that signaling pathways activated by both BAFF and ARRIL in mammary gland point towards NF-${\kappa}$B activation which causes upregulation of bax.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5807-5815
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• 2015

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

• Bulletin of the Korean Chemical Society
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• v.30 no.7
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• pp.1573-1578
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• 2009

A computational study of the reactions between Zn-containing species, the products of the thermal decomposition of diethylzinc (DEZn) and water was investigated. The Zn-containing species – $C_2H_5)_2,\;HZnC_2H_5,\;and\;(ZnC_2H_5)_2$ – were assumed to react with water during ZnO metal organic chemical vapor deposition (MOCVD). Density functional theory (DFT) calculations at the level of B3LYP/6-311G(d) were employed for the geometry optimization and thermodynamic property evaluation. As a result dihydroxozinc, $Zn(OH)_2$, was the most probable reaction product common for all three Zn-containing species. A further clustering of $Zn(OH)_2$ was investigated to understand the initial stage of ZnO film deposition. In experiments, the reactions of DEZn and water were examined by in-situ Raman scattering in a specially designed MOCVD reactor. Although direct evidence of $Zn(OH)_2$ was not observed, some relevant reaction intermediates were successfully detected to support the validity of the gas phase reaction pathways proposed in the computational study.

• Journal of Embryo Transfer
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• v.20 no.3
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• pp.191-200
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• 2005

Many studies have shown that the development of mouse early 2-cell embryos in vitro is related with the intracellular $Ca^{2+}$ changes. In ICR strain mouse, the development of embryos arrests at early 2-cell stage, but the arrested early 2-cell embryos can be rescued by the addition of $Ca^{2+}$-related materials. Acetylcholine (ACh) increases intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) via the mAChR-PLC-IP3 pathway in mouse oocytes. We examined whether ACh rescues 2-cell block in mouse. In early 2-cell embryos, ACh increased [$Ca^{2+}$]i in a dose-dependent manner (p<0.001), and had an effect on rescue of 2-cell block and embryonic development. To identify the signal pathway involved in ACh-induced rescue of 2-cell block, we first applied an agonist of ACh receptor (AChR). Like ACh, carbachol increased intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) and atropine, an antagonist of ACh receptor, blocked the ACh-induced $Ca^{2+}$ increase. In $Ca^{2+}$-free medium, ACh also increased [$Ca^{2+}$]i, indicating that $Ca^{2+}$ increased by ACh is mainly released from the intracellular $Ca^{2+}$ store. The ACh-induced $Ca^{2+}$ increase was blocked by PLC inhibitor (U73122), ryanodine receptor (RyR) antagonist (dantrolene), and CaM KII inhibitor (KN-93), but not by IP3R antagonists (xestospongin C). These results show that ACh increases intracellular $Ca^{2+}$ concentration via mAChR/PLC/RyR, and this contributes to the rescue of 2-cell block.

• Journal of Intelligence and Information Systems
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• v.26 no.3
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• pp.127-147
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• 2020

The world is suffering from numerous human and economic losses due to the novel coronavirus infection (COVID-19). The Korean government established a strategy to overcome the national infectious disease crisis through research and development. It is difficult to find distinctive features and changes in a specific R&D field when using the existing technical classification or science and technology standard classification. Recently, a few studies have been conducted to establish a classification system to provide information about the investment research areas of infectious diseases in Korea through a comparative analysis of Korea government-funded research projects. However, these studies did not provide the necessary information for establishing cooperative research strategies among countries in the infectious diseases, which is required as an execution plan to achieve the goals of national health security and fostering new growth industries. Therefore, it is inevitable to study information services based on the classification system and classification model for establishing a national collaborative R&D strategy. Seven classification - Diagnosis_biomarker, Drug_discovery, Epidemiology, Evaluation_validation, Mechanism_signaling pathway, Prediction, and Vaccine_therapeutic antibody - systems were derived through reviewing infectious diseases-related national-funded research projects of South Korea. A classification system model was trained by combining Scopus data with a bidirectional RNN model. The classification performance of the final model secured robustness with an accuracy of over 90%. In order to conduct the empirical study, an infectious disease classification system was applied to the coronavirus-related research and development projects of major countries such as the STAR Metrics (National Institutes of Health) and NSF (National Science Foundation) of the United States(US), the CORDIS (Community Research & Development Information Service)of the European Union(EU), and the KAKEN (Database of Grants-in-Aid for Scientific Research) of Japan. It can be seen that the research and development trends of infectious diseases (coronavirus) in major countries are mostly concentrated in the prediction that deals with predicting success for clinical trials at the new drug development stage or predicting toxicity that causes side effects. The intriguing result is that for all of these nations, the portion of national investment in the vaccine_therapeutic antibody, which is recognized as an area of research and development aimed at the development of vaccines and treatments, was also very small (5.1%). It indirectly explained the reason of the poor development of vaccines and treatments. Based on the result of examining the investment status of coronavirus-related research projects through comparative analysis by country, it was found that the US and Japan are relatively evenly investing in all infectious diseases-related research areas, while Europe has relatively large investments in specific research areas such as diagnosis_biomarker. Moreover, the information on major coronavirus-related research organizations in major countries was provided by the classification system, thereby allowing establishing an international collaborative R&D projects.

• Proceedings of the Technology Innovation Conference
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• 1997.07a
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• pp.222-223
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• 1997

By analyzing the successful innovation case of potato microtuber mass production technology, a representative case of technology-push type creative innovation in an imitation oriented research culture, this paper attempts to figure out conceptual model of creative innovation that is initiated by the public laboratories in catching-up country, Stages of creative innovation can be divided into the internal R&D stage and the external commercialization stage. Success of the internal R&D stage depended on autonomy to secure creative research idea and commitment of individual researchers. Psychological pressure evoked from sportlights of mass media and commitment of sponsor increased the intensity of research efforts of the researcher Recognition of research problem and its significance was intensified by site visits of agricultural fields, and the recognized higher impacts of expected research results and knowledge creation achieved were a fundamental source of self-motivation. In the stage of commercialization stage, various legal, socio-economic, and psychological barriers were confronted. In a catching-up country lacking of experiences of creative innovation, creative innovation process can be regarded as a barrier elimination and cultural revolution process. Among the barriers, psychological refusal of farmers to corn-sized potato seeds was critical, which finally enforced to further researches to enlarge the size of potato seeds. In addition, the researcher has concentrated his research efforts in one specialized research area by getting a series of similar research project funds rather than diversification. It was lucky for him to have a chance to carry out a series of similar researches in one research area during the last 10 years. In getting research funds from government and private companies continuously in one research area, both internal and external promoters played significant roles.