• Title/Summary/Keyword: Disruption

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Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

  • Song, Chin-Hee;Kim, Nayoung;Sohn, Sung Hwa;Lee, Sun Min;Nam, Ryoung Hee;Na, Hee Young;Lee, Dong Ho;Surh, Young-Joon
    • Gut and Liver
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    • v.12 no.6
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    • pp.682-693
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    • 2018
  • Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

Safety Risk Management Policy of United States small unmanned aerial system (미 소형 무인비행체계의 안전성 위험관리 정책)

  • Hong, Jin-Keun
    • Journal of Convergence for Information Technology
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    • v.11 no.9
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    • pp.35-42
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    • 2021
  • The purpose of this paper is to review the small unmanned aerial system (sUAS) safety policy promoted by the United States(US) government. Therefore, in this paper, along with sUAS risk factors, the risk factors of sUAS that the US government is interested in are described. In addition, the risk factors were classified into physical and non-physical factors, and provisions mentioned in the Federal Aviation Administration(FAA) Relicensing Act were reviewed. Other risk scenarios were analyzed focusing on target scenario items that the FAA is interested in, such as flight operation disruption, infrastructure damage, and facility trespassing. Of course, we looked at the risk management principles promoted by the US FAA. In this paper, as a research method, the direction and contents of the FAA's sUAS policy were studied and reviewed from the analysis of major foreign journals and policy. In the research result of this paper, by analyzing the FAA sUAS safety risk management policy, the integrated operation and safety policy, physical risk management policy, operation and safety regulation, and sUAS policy and technology direction necessary for establishing the sUAS safety risk management guide in Korea are presented. The contribution of this study is to identify the leading US sUAS safety policy direction, and it can be used as basic data for deriving future domestic policy directions from this. Based on the research results presented in the future, policy studies are needed to derive detailed implementation plans.

Construction of Yeast Strain Suitable for Bioethanol Production by Using Fusion Method (융합법을 이용한 바이오에탄올 생산에 적합한 효모균주의 구축)

  • Kim, Yeon-Hee
    • Journal of Life Science
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    • v.29 no.3
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    • pp.376-381
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    • 2019
  • To construct useful yeast strain for bioethanol production, we improved yeast harboring various phenotypes by using yeast protoplast fusion method. In this study, S. cerevisiae BYK-F11 strain which have ethanol tolerance, thermotolerance and ${\beta}-glucanase$ activity and P. $stipitis{\Delta}ura$ strain which has xylose metabolism pathway were fused by genome shuffling. P. $stipitis{\Delta}ura$ strain was constructed for protoplast fusion by URA3 gene disruption, resulting in uracil auxotroph. By protoplast fusion, several fused cells were selected and BYKPS-F8 strain (fused cell) showing both karyotypes from two parent strains (S. cerevisiae BYK-F11 and P. $stipitis{\Delta}ura$ strain) among 22 fused cells was finally selected. Sequentially, various phenotypes such as ${\beta}-glucanase$ activity, xylose utility, ethanol tolerance, thermotolerance and ethanol productivity were analyzed. The BYKPS-F8 strain obtained ${\beta}-glucanase$ activity from BYK-F11 strain and 1.2 fold increased xylose utility from P. $stipitis{\Delta}ura$ strain. Also, the BYKPS-F8 strain showed thermotolerance at $40^{\circ}C$ and increased ethanol tolerance in medium containing 8% ethanol. In this fused cell, 7.5 g/l ethanol from 20 g/l xylose was produced and the multiple phenotypes were stably remained during long term cultivation (260 hr). It was proved that novel biological system (yeast strains) is easily and efficiently bred by protoplast fusion among yeasts having different genus.

Increased Apoptotic Efficacy of Decitabine in Combination with an NF-kappaB Inhibitor in Human Gastric Cancer AGS Cells (핵산합성 억제제인 decitabine과 NF-κB 활성 저해제인 PDTC의 병용 처리에 의한 인체 위암세포사멸 효과 증진)

  • Choe, Won Kyung;Choi, Yung Hyun
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1268-1276
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    • 2018
  • The cytidine analog decitabine (DEC) acts as a nucleic acid synthesis inhibitor, whereas ammonium pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor-${\kappa}B$. The aim of this study was to investigate the possible synergistic inhibitory effect of these two inhibitors on proliferation of human gastric cancer AGS cells. The inhibitory effect of PDTC on AGS cell proliferation was significantly increased by DEC in a concentration-dependent manner, and this inhibition was associated with cell cycle arrest at the G2/M phase and the induction of apoptosis. This induction of apoptosis by the co-treatment with PDTC and DEC was related to the induction of DNA damage, as assessed by H2AX phosphorylation. Further studies demonstrated that co-treatment with PDTC and DEC induced the disruption of mitochondrial membrane potential, increased the generation of intracellular reactive oxygen species (ROS) and the expression of pro-apoptotic Bax, and down-regulated the expression of anti-apoptotic Bcl-2, ultimately resulting in the release of cytochrome c from the mitochondria into the cytoplasm. Co-treatment with PDTC and DEC also activated caspase-8 and caspase-9, which are representative caspases of the extrinsic and intrinsic apoptosis pathways. Co-treatment also activated caspase-3, which was accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Taken together, these data clearly indicated that co-treatment with PDTC and DEC suppressed the proliferation of AGS cells by increasing DNA damage and activating the ROS-mediated extrinsic and intrinsic apoptosis pathways.

Selection of Vaccinia Virus-Neutralizing Antibody from a Phage-Display Human-Antibody Library

  • Shin, Yong Won;Chang, Ki-Hwan;Hong, Gwang-Won;Yeo, Sang-Gu;Jee, Youngmee;Kim, Jong-Hyun;Oh, Myoung-don;Cho, Dong-Hyung;Kim, Se-Ho
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.651-657
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    • 2019
  • Although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. Smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. Passive administration of neutralizing monoclonal antibodies (mAbs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. Currently, vaccinia immune globulin (VIG) is manufactured from vaccinia vaccine-boosted plasma; however, this production method is not ideal because of its limited availability, low specific activity, and risk of contamination with blood-borne infectious agents. To overcome the limitations of VIG production from human plasma, we isolated two human single-chain variable fragments (scFvs), (SC34 and SC212), bound to vaccinia virus (VACV), from a scFv phage library constructed from the B cells of VACV vaccine-boosted volunteers. The scFvs were converted to human IgG1 (VC34 and VC212). These two anti-VACV mAbs were produced in Chinese Hamster Ovary (CHO) DG44 cells. The binding affinities of VC34 and VC212 were estimated by competition ELISA to $IC_{50}$ values of $2{\mu}g/ml$ (13.33 nM) and $22{\mu}g/ml$ (146.67 nM), respectively. Only the VC212 mAb was proven to neutralize the VACV, as evidenced by the plaque reduction neutralization test (PRNT) result with a $PRNT_{50}$ of ~0.16 mg/ml (${\sim}1.07{\mu}M$). This VC212 could serve as a valuable starting material for further development of VACV-neutralizing human immunoglobulin for a prophylactic measure against post-vaccination complications and for post-exposure treatment against smallpox.

N-Acyl-Homoserine Lactone Quorum Sensing Switch from Acidogenesis to Solventogenesis during the Fermentation Process in Serratia marcescens MG1

  • Jin, Wensong;Lin, Hui;Gao, Huifang;Guo, Zewang;Li, Jiahuan;Xu, Quanming;Sun, Shujing;Hu, Kaihui;Lee, Jung-Kul;Zhang, Liaoyuan
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.596-606
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    • 2019
  • N-acyl-homoserine lactone quorum sensing (AHL-QS) has been shown to regulate many physiological behaviors in Serratia marcescens MG1. In the current study, the effects of AHL-QS on the biosynthesis of acid and neutral products by S. marcescens MG1 and its isogenic ${\Delta}swrI$ with or without supplementing exogenous N-hexanoyl-L-homoserine lactone ($C_6-HSL$) were systematically investigated. The results showed that swrI disruption resulted in rapid pH drops from 7.0 to 4.8, which could be restored to wild type by supplementing $C_6-HSL$. Furthermore, fermentation product analysis indicated that ${\Delta}swrI$ could lead to obvious accumulation for acidogenesis products such as lactic acid and succinic acid, especially excess acetic acid (2.27 g/l) produced at the early stage of fermentation, whereas solventogenesis products by ${\Delta}swrI$ appeared to noticeably decrease by an approximate 30% for acetoin during 32-48 h and by an approximate 20% for 2,3-butanediol during 24-40 h, when compared to those by wild type. Interestingly, the excess acetic acid produced could be removed in an AHL-QS-independent manner. Subsequently, quantitative real-time PCR was used to determine the mRNA expression levels of genes responsible for acidogenesis and solventogenesis and showed consistent results with those of product synthesis. Finally, by close examination of promoter regions of the analyzed genes, four putative luxI box-like motifs were found upstream of genes encoding acetyl-CoA synthase, lactate dehydrogenase, ${\alpha}$-acetolactate decarboxylase, and Lys-like regulator. The information from this study provides a novel insight into the roles played by AHL-QS in switching from acidogenesis to solventogenesis in S. marcescens MG1.

The Effect of Leukoaraiosis on the Severity and Course of Delirium (백질변성이 섬망의 심각도 및 경과에 미치는 영향)

  • Choi, Won-Jung;Seok, Jeong-Ho;Oh, Seung-Taek;Chung, Tae-Sub;Kim, Jae-Jin
    • Korean Journal of Psychosomatic Medicine
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    • v.26 no.2
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    • pp.194-200
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    • 2018
  • Objectives : The significance of leukoaraiosis on brain magnetic resonance imaging (MRI) is uncertain, but it is often seen with vascular risk factors or in the context of cognitive impairment. We aimed to investigate the effect of leukoaraiosis on the severity and course of delirium. Methods : Periventricular hyperintensity and deep white matter hyperintensity on brain MRI were rated in 42 patients with delirium by semiquantative visual rating scale. Correlations between their grades and the scores of Korean version of Delirium Rating Scale-Revised-98 (K-DRS-R-98) were analyzed, and the interaction effects between the groups according to the levels of leukoaraiosis and two evaluation points were also analyzed. Results : The grade of deep white matter hyperintensity in the occipital lobe was positively correlated with the scores on the total, severity items, cognitive items, and non-cognitive items of K-DRS-R-98. The cognitive items scores of K-DRS-R-98 in the low grade group of periventricular hyperintensity showed significantly steeper decrease than the high grade group. Conclusions : A difference in severity or recovery speed of delirium according to the level of leukoaraiosis may result from disruption in brain functional connectivity. Our results have a clinical implication in that the severity and course of delirium can be possibly predicted using the level of leukoaraiosis.

Clinical Significance of Preoperative Embolization for Non-Hypervascular Metastatic Spine Tumors

  • Yoo, Sung-Lim;Kim, Young-Hoon;Park, Hyung-Youl;Kim, Sang-Il;Ha, Kee-Yong;Min, Hyung-Ki;Seo, Jun-Yeong;Oh, In-Soo;Chang, Dong-Gune;Ahn, Joo-Hyun;Kim, Yong-Woo
    • Journal of Korean Neurosurgical Society
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    • v.62 no.1
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    • pp.106-113
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    • 2019
  • Objective : The efficacy of preoperative embolization for hypervascular metastatic spine disease (MSD) such as renal cell and thyroid cancers has been reported. However, the debate on the efficacy of preoperative embolization for non-hypervascular MSD still remains unsettled. The purpose of this study is to determine whether preoperative embolization for non-hypervascular MSD decreases perioperative blood loss. Methods : A total of 79 patients (36 cases of preoperative embolization and 43 cases of non-embolization) who underwent surgery for metastatic spine lesions were included. Representative hypervascular tumors such as renal cell and thyroid cancers were excluded. Intraoperative and perioperative estimated blood losses (EBL), total number of transfusion and calibrated EBL were recorded in the embolization and non-embolization groups. The differences in EBL were also compared along with the type of surgery. In addition, the incidence of Adamkiewicz artery and complications of embolization were assessed. Results : The average age of 50 males and 29 females was $57.6{\pm}13.5$ years. Lung (30), hepatocellular (14), gastrointestinal (nine) and others (26) were the primary cancers. The demographic data was not significantly different between the embolization and the non-embolization groups. There were no significant differences in intraoperative EBL, perioperative EBL, total transfusion and calibrated EBL between two groups. However, intraoperative EBL and total transfusion in patients with preoperative embolization were significantly lower than in non-embolization in the corpectomy group (1645.5 vs. 892.6 mL, p=0.017 for intraoperative EBL and 6.1 vs. 3.9, p=0.018 for number of transfusion). In addition, the presence of Adamkiewicz artery at the index level was noted in two patients. Disruption of this major feeder artery resulted in significant changes in intraoperative neuromonitoring. Conclusion : Preoperative embolization for non-hypervascular MSD did not reduce perioperative blood loss. However, the embolization significantly reduced intraoperative bleeding and total transfusion in corpectomy group. Moreover, the procedure provided insights into the anatomy of tumor and spinal cord vasculature.

Jonjae Wie Baek-Gyu's Thoughts & Proposals for Educational Reform and the implication of moral education (존재(存齋) 위백규(魏伯珪)의 교육개혁론(敎育改革論)과 그 도덕교육적(道德敎育的) 함의(含意))

  • Park, Hakrae
    • (The)Study of the Eastern Classic
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    • no.72
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    • pp.265-298
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    • 2018
  • This paper examines the contents and meaning of the education reform theory among the social reform theory of Wie Baek-gyu(1727~1798), a representative Confucian scholar of Honam in the 18th century, and suggests the moral educational implications of his educational reform theory. Wie Baek-gyu, who lived through the Yeongjo and Jeongjo eras, diagnosed the contradictions and problems of society at that time as the absence of morality. And emphasized the reform of school education as a center of ways to overcome social disruption. The educational reform theory he envisioned was to systematize the process from child education to higher education centered on the system reorganization of the school, and to formulate school education in conjunction with the selection of talent. He emphasized the cultivation and practice of moral character in the course of admission and curriculum of the school, and suggested a system that reflects the opinions of the local people in the admission process, thereby establishing the school as the center of the local society. His educational reform theory, which embodies the school system based on moral education and further shapes the school system and educational contents as the center of edification and recruitment of talented people, is a big indication of the curriculum of the current moral curriculum that emphasizes the cultivation and practice of inner morality based on personality education. In this paper, I summarized and reviewed the general contents of his perception of the times and social reform theory, the diagnosis of the educational reality that is the basis of his educational reform theory, and the specific contents of the education reform theory. Based on this, I presented the meaning to the current moral and curriculum.

Toegye's Tao-hsueh and the Theory of Governance (퇴계(退溪)의 도학(道學)과 경세론(經世論))

  • Kang, Heui Bok
    • The Journal of Korean Philosophical History
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    • no.41
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    • pp.71-92
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    • 2014
  • A series of the tragic 16th-century Sahwas sent Toegye into the depths of despair. In the face of the ensuing social disruption in which any criterion or direction is utterly lost, he could not but to reexamine the problem of human nature and good and evil. For Toegye, criterion or direction is connected with Principle, and human nature and the problem of good and evil are related with Mind. In other words, these problems are none other than the question: "As the subject of history and society, how a human being can set principle in a real world and realize it? How one can successfully control his wants and feelings with his rationality?" Toegye proposes that while laws and regulations should be reformed when they are outdated, good laws and regulations are not necessarily to be discarded. He also warns that ideal governance is not likely to be realized if only too conservatives take the lead while radicals, depended upon exclusively, would create too many problems.