• Title/Summary/Keyword: Regulatory mechanisms

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DNA Demethylation of the Foxp3 Enhancer Is Maintained through Modulation of Ten-Eleven-Translocation and DNA Methyltransferases

  • Nair, Varun Sasidharan;Song, Mi Hye;Ko, Myunggon;Oh, Kwon Ik
    • Molecules and Cells
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    • v.39 no.12
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    • pp.888-897
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    • 2016
  • Stable expression of Foxp3 is ensured by demethylation of CpG motifs in the Foxp3 intronic element, the conserved non-coding sequence 2 (CNS2), which persists throughout the lifespan of regulatory T cells (Tregs). However, little is known about the mechanisms on how CNS2 demethylation is sustained. In this study, we found that Ten-Eleven-Translocation (Tet) DNA dioxygenase protects the CpG motifs of CNS2 from re-methylation by DNA methyltransferases (Dnmts) and prevents Tregs from losing Foxp3 expression under inflammatory conditions. Upon stimulation of Tregs by interleukin-6 (IL6), Dnmt1 was recruited to CNS2 and induced methylation, which was inhibited by Tet2 recruited by IL2. Tet2 prevented CNS2 re-methylation by not only the occupancy of the CNS2 locus but also by its enzymatic activity. These results show that the CNS2 methylation status is dynamically regulated by a balance between Tets and Dnmts which influences the expression of Foxp3 in Tregs.

Safety Regulation of Enhanced In-Service Inspection(ISI) in Nuclear Power Plant (원자력발전소 강화 가동중검사 안전규제)

  • Shin, Ho-Sang
    • Journal of the Korean Society for Nondestructive Testing
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    • v.30 no.4
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    • pp.380-385
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    • 2010
  • The integrity of components and piping of operating nuclear power plants has been identified by in-service inspection(ISI) requirements and activities commensurate with standards and codes such as KEPIC MI or ASME Code Section XI. However, the other various degradation mechanisms not considered during design stage of nuclear power plants have been checked by enhanced ISI. The requirements of enhanced ISI have been voluntarily developed by the industry itself or strickly issued by regulatory body. Even though the requirements were developed by the industry, they should be reviewed by regulatory body for their application in nuclear power plants. The enhanced ISI activities and requirements of non-destructive examination(NDE) which reflect the degradation issues in nuclear power industry will be primarily discussed in this paper.

Secure Electronic Ticketing System based on Consortium Blockchain

  • Li, Xuelian;Niu, Jie;Gao, Juntao;Han, Yue
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.13 no.10
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    • pp.5219-5243
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    • 2019
  • In electronic ticketing system, the malicious behavior of scalpers damages the customer's interest and disturbs the normal order of market. In order to solve the problem of scalpers, we took two steps. Firstly, we established the electronic ticketing system based on the consortium blockchain (CB-ETS). By establishing CB-ETS, we can make the ticketing market develop better in a controlled environment and be managed by the members in the consortium blockchain. Secondly, we put forward a kind of taxation mechanism for suppressing scalpers based on CB-ETS. Together with the regulatory mechanism, our scheme can effectively reduce the scalpers' profits and further inhibit scalpers. Through the above two steps, the scheme can effectively resist the malicious behavior of scalpers. Among them, in the process of transferring tickets, we optimized the transfer mechanism to achieve a win-win situation. Finally, we analyzed the security and efficiency of our scheme. Our scheme realizes the anonymity through the mixed currency protocol based on ring signature and guarantees the unforgeability of tickets by multi-signature in the process of modifying the invalidity of tickets. It also could resist to Dos attacks and Double-Spending attacks. The efficiency analysis shows that our scheme is significantly superior to relevant works.

HUMAN ERRORS DURING THE SIMULATIONS OF AN SGTR SCENARIO: APPLICATION OF THE HERA SYSTEM

  • Jung, Won-Dea;Whaley, April M.;Hallbert, Bruce P.
    • Nuclear Engineering and Technology
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    • v.41 no.10
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    • pp.1361-1374
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    • 2009
  • Due to the need of data for a Human Reliability Analysis (HRA), a number of data collection efforts have been undertaken in several different organizations. As a part of this effort, a human error analysis that focused on a set of simulator records on a Steam Generator Tube Rupture (SGTR) scenario was performed by using the Human Event Repository and Analysis (HERA) system. This paper summarizes the process and results of the HERA analysis, including discussions about the usability of the HERA system for a human error analysis of simulator data. Five simulated records of an SGTR scenario were analyzed with the HERA analysis process in order to scrutinize the causes and mechanisms of the human related events. From this study, the authors confirmed that the HERA was a serviceable system that can analyze human performance qualitatively from simulator data. It was possible to identify the human related events in the simulator data that affected the system safety not only negatively but also positively. It was also possible to scrutinize the Performance Shaping Factors (PSFs) and the relevant contributory factors with regard to each identified human event.

Beyond gene expression level: How are Bayesian methods doing a great job in quantification of isoform diversity and allelic imbalance?

  • Oh, Sunghee;Kim, Chul Soo
    • Journal of the Korean Data and Information Science Society
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    • v.27 no.1
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    • pp.225-243
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    • 2016
  • Thanks to recent advance of next generation sequencing techniques, RNA-seq enabled to have an unprecedented opportunity to identify transcript variants with isoform diversity and allelic imbalance (Anders et al., 2012) by different transcriptional rates. To date, it is well known that those features might be associated with the aberrant patterns of disease complexity such as tissue (Anders and Huber, 2010; Anders et al., 2012; Nariai et al., 2014) specific differential expression at isoform levels or tissue specific allelic imbalance in mal-functionality of disease processes, etc. Nevertheless, the knowledge of post-transcriptional modification and AI in transcriptomic and genomic areas has been little known in the traditional platforms due to the limitation of technology and insufficient resolution. We here stress the potential of isoform variability and allelic specific expression that are relevant to the abnormality of disease mechanisms in transcriptional genetic regulatory networks. In addition, we systematically review how robust Bayesian approaches in RNA-seq have been developed and utilized in this regard in the field.

MiT Family Transcriptional Factors in Immune Cell Functions

  • Kim, Seongryong;Song, Hyun-Sup;Yu, Jihyun;Kim, You-Me
    • Molecules and Cells
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    • v.44 no.5
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    • pp.342-355
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    • 2021
  • The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

A network-biology approach for identification of key genes and pathways involved in malignant peritoneal mesothelioma

  • Mahfuz, A.M.U.B.;Zubair-Bin-Mahfuj, A.M.;Podder, Dibya Joti
    • Genomics & Informatics
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    • v.19 no.2
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    • pp.16.1-16.14
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    • 2021
  • Even in the current age of advanced medicine, the prognosis of malignant peritoneal mesothelioma (MPM) remains abysmal. Molecular mechanisms responsible for the initiation and progression of MPM are still largely not understood. Adopting an integrated bioinformatics approach, this study aims to identify the key genes and pathways responsible for MPM. Genes that are differentially expressed in MPM in comparison with the peritoneum of healthy controls have been identified by analyzing a microarray gene expression dataset. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of these differentially expressed genes (DEG) were conducted to gain a better insight. A protein-protein interaction (PPI) network of the proteins encoded by the DEGs was constructed using STRING and hub genes were detected analyzing this network. Next, the transcription factors and miRNAs that have possible regulatory roles on the hub genes were detected. Finally, survival analyses based on the hub genes were conducted using the GEPIA2 web server. Six hundred six genes were found to be differentially expressed in MPM; 133 are upregulated and 473 are downregulated. Analyzing the STRING generated PPI network, six dense modules and 12 hub genes were identified. Fifteen transcription factors and 10 miRNAs were identified to have the most extensive regulatory functions on the DEGs. Through bioinformatics analyses, this work provides an insight into the potential genes and pathways involved in MPM.

Recent Advances in Cell Therapeutics for Systemic Autoimmune Diseases

  • Youngjae Park;Seung-Ki Kwok
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.10.1-10.17
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    • 2022
  • Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

Regulatory Mechanisms of Annexin-Induced Chemotherapy Resistance in Cisplatin Resistant Lung Adenocarcinoma

  • Wang, Chao;Xiao, Qian;Li, Yu-Wen;Zhao, Chao;Jia, Na;Li, Rui-Li;Cao, Shan-Shan;Cui, Jia;Wang, Lu;Wu, Yin;Wen, Ai-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3191-3194
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    • 2014
  • Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.

What makes Consumers to Prolong their Consumption on Perishable Food beyond Its Expiration Date?

  • Suh, Hyunsuk;Ju, Hyoungjun
    • Asia Marketing Journal
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    • v.15 no.2
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    • pp.133-173
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    • 2013
  • Consumers empty perfectly safe to intake perishable foods everyday if they are older than what prints on expiration date. The variation in expiration dating is freshness labeling represented in various terms such as sell by, package, best before, and so on. Regardless of the terms used and meanings are attached, consumers tend to conceive of freshness labeling on food as end of its shelf-life. Consequently, the food waste becomes a big issue for businesses in food sector. In an effort to demonstrate flexibility on this, KFDA(Korea Food & Drug Administration) introduced "best before" date in domestic market place to reduce food waste, based on the food safety test conducted by KCA(Korea Consumer Agency 2009). The results indicated freshness labeling on food should not be considered as the end of its life. Current study examined the underlying mechanisms(i.e. risk perception, self-construals, and indecisiveness) that influence consumers' intention on prolonged consumption of food beyond its stamped date when the KCA test results are shown to them. In addition, the moderating effect of regulatory focus is tested in the causal relationships between underlying mechanisms and different groups of prolonged consumption intention. Study participants are divided into three groups of prolonged consumption intention: no-change, moderate-change, and wide-change. The group with moderate-change in intention being as our point of reference, logistic regression analyses are conducted on 276 sample population. The results indicated that consumers with high source credibility risk are likely to show wide-change in intention on prolonged consumption while physical risk did not show significance. The consumers with independent self-construal are likely to show no-change in intention on prolonged consumption while interdependent self-construal did not show significance. Indecisiveness showed association a group with wide-change in intention on prolonged consumption. The moderating effect of regulatory focus showed valid results in most situations; the promotion-focused consumers showed wide-change in intention, while prevention-focused consumers showed no-change in intention. Furthermore, the moderating effect of promotion-focus showed a dominant position over the causal effect of indecisiveness in which decisive consumers(i.e. no-change in intention); if they are promotion-focused they tend show for the wide-change in intention instead. It is important to note that for those promotion-focused consumers(or situations), promotion-related arguments are more effective, while for those prevention-focused consumers(or situations) prevention- related arguments are more effective means of persuasion.

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