Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells

Kim, Dong Eon,Jang, Mi-Jin,Kim, Young Ran,Lee, Joo-Young,Cho, Eun Byul,Kim, Eunha,Kim, Yeji,Kim, Mi Young,Jeong, Won-il,Kim, Seyun,Han, Yong-Mahn,Lee, Seung-Hyo Elsevier 2017 Toxicology Vol.387 No.-

<P><B>Abstract</B></P> <P>Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an <I>in vitro</I> model system for assessment of drug-induced as well as immune-mediated hepatotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Generation and characterization of hES-HLCs for evaluation of drug-induced immune cell-mediated hepatotoxicity. </LI> <LI> The secretion of inflammatory cytokines is highly enhanced from APAP-treated hES-HLCs. </LI> <LI> Immune cells are activated and produce pro-inflammatory cytokines by conditioned medium from hES-HLCs cultured with APAP. </LI> <LI> Hepatotoxic results in hES-HLCs are consistent with those of primary human hepatocytes. </LI> <LI> Hepatotoxic drugs such as TZD, and non-hepatotoxic drugs such as aspirin and metformin, are also validated with our drug screening system. </LI> </UL> </P>

Exploring Nuclear Functions of Inositol Polyphosphate Multikinase in the Control of Growth and Metabolism

Seyun Kim 한국실험동물학회 2015 한국실험동물학회 학술발표대회 논문집 Vol.2015 No.8

Rhodium-Catalyzed Carbonylative [3 + 2 + 1] Cycloaddition of Alkyne-Tethered Alkylidenecyclopropanes to Phenols in the Presence of Carbon Monoxide

Kim, Seyun,Chung, Young Keun American Chemical Society 2014 ORGANIC LETTERS Vol.16 No.17

<P>A novel Rh-catalyzed carbonylative [3 + 2 + 1] cycloaddition of alkyne-tethered alkylidenecyclopropanes for the facile synthesis of bicyclic phenols in high yields has been developed. The reaction tolerated carbon and heteroatoms in the tether.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2014/orlef7.2014.16.issue-17/ol5015224/production/images/medium/ol-2014-015224_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol5015224'>ACS Electronic Supporting Info</A></P>

Lossless Compression of Color Filter Array Images by Hierarchical Prediction and Context Modeling

Seyun Kim,Nam Ik Cho IEEE 2014 IEEE transactions on circuits and systems for vide Vol.24 No.6

<P>This paper presents an encoder for the lossless compression of color filter array (CFA) data, which consists of a hierarchical predictor and context-adaptive arithmetic encoder. In hierarchical prediction, the subsampled images are encoded in order; each of the subimages contains only one color component (red, green, or blue) in the case of a Bayer CFA image. By subsampling, the green pixels are separated into two sets, one of which is encoded by a conventional grayscale encoder, and then is used to predict the green pixels in the other set. Both the sets of greens are then used to predict the reds, and the green and red pixels are used to predict the blues. Throughout this process, the predictors are designed considering the direction of the edges in the neighborhood. By gathering some information from the prediction process, such as edge activity and neighboring errors, the magnitude of prediction error is also estimated. From this, the probability distribution function of prediction error conditioned on neighboring pixels, i.e., the context is estimated, and context-adaptive arithmetic encoding is applied to reduce the resulting bits further. The experimental results on real and simulated CFA images show that the proposed method produces less bits per pixel than the conventional lossless image compression methods and recently developed lossless CFA compression algorithms.</P>

Hierarchical Prediction and Context Adaptive Coding for Lossless Color Image Compression

Seyun Kim,Nam Ik Cho IEEE 2014 IEEE TRANSACTIONS ON IMAGE PROCESSING - Vol.23 No.1

<P>This paper presents a new lossless color image compression algorithm, based on the hierarchical prediction and context-adaptive arithmetic coding. For the lossless compression of an RGB image, it is first decorrelated by a reversible color transform and then Y component is encoded by a conventional lossless grayscale image compression method. For encoding the chrominance images, we develop a hierarchical scheme that enables the use of upper, left, and lower pixels for the pixel prediction, whereas the conventional raster scan prediction methods use upper and left pixels. An appropriate context model for the prediction error is also defined and the arithmetic coding is applied to the error signal corresponding to each context. For several sets of images, it is shown that the proposed method further reduces the bit rates compared with JPEG2000 and JPEG-XR.</P>

Removing False Contour Artifact for Bit-depth Expansion

Kim, Seyun,Choo, Sungkwon,Cho, Nam Ik The Institute of Electronics and Information Engin 2013 IEIE Transactions on Smart Processing & Computing Vol.2 No.2

Bit-depth expansion is a process of enhancing the image quality by increasing the number of intensity levels. To solve this problem, a hybrid method is proposed, where the pixels are categorized into smooth and complex regions, and are processed using different methods. The pixels in the smooth region are reconstructed with a smooth prior, and a Bayesian estimator is used for the pixels in the complex region. The proposed method effectively removes the false contour artifacts while requiring less computation than conventional methods. In addition, the method shows good quantitative performance, and the PSNR gains over the best existing method are 1.45 dB and 0.26 dB for 4 bits and 3 bits expansion cases, respectively.

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

Kim, Eunha,Tyagi, Richa,Lee, Joo-Young,Park, Jina,Kim, Young-ran,Beon, Jiyoon,Chen, Po Yu,Cha, Jiyoung Y.,Snyder, Solomon H.,Kim, Seyun National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.49

<P>Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes.</P>

Effects of Informatization Mind on Information Development Efforts and Academic Achievement of University Students Major in Sports

Kim, Seyun The Institute of Internet 2021 International Journal of Internet, Broadcasting an Vol.13 No.2

The purpose of this study is to identify the impact of informatization minds of college students majoring in sports on information development efforts and academic achievement. Accordingly, a survey was conducted on 200 college students majoring in physical education at D University, and 197 students were selected as the final effective samples. Data processing was conducted using SPSS 23 for frequency analysis, reliability analysis, correlation analysis, and regression analysis. The results are as follows: First, recognition of the necessity of informatization education, a subfactor of the informatization mind, has a positive impact on informatino development efforts. Second, recognition of the necessity of informatization education, understanding and utilization of informatization concepts among sub-factors of informatization minds have a positive impact on the major learning achievement. Third, all the conversational factors in the informatization mind have a positive impact on study problem resolution. Fourth, information development efforts have a positive impact on the major learning achievement and the study problem resolution. Therefore, efforts are needed to increase the information mindset of college students major in sports.

The Effects of E-sports Broadcasting Commentator's Attributes on Broadcasting Attitude and Continuous Viewing Intention

Kim, Seyun The Institute of Internet 2021 International journal of advanced smart convergenc Vol.10 No.1

The purpose of this study is to determine the impact of broadcasters' broadcasting commentators' attributes on broadcasting conditions and the intention of continuous viewing of e-sports competitions. To achieve this goal, a survey was conducted on 300 university students who had experience watching e-sports competition broadcasting. The final 295 copies were selected as the final valid samples and data processing was carried out. Using SPSS 23, factor analysis, reliability analysis, correlation analysis, and simple and multiple regression analysis were performed. The result of this study was: First, reliability and attractiveness among the sub-factors of commentator attributes were shown to have a positive effect on broadcasting conditions. Second, reliability and attractiveness among the sub-factors of commentator attributes have a positive effect on the intent of continuous viewing. Third, broadcasting conditions have a positive effect on the intention of continuous viewing.

On node criticality of the Northeast Asian air route network

Kim, Seyun,Yoon, Yoonjin Elsevier 2019 Journal of air transport management Vol.80 No.-

<P><B>Abstract</B></P> <P>In this paper, air route network robustness of the rapidly growing Northeast Asian region is assessed based on the node criticality. Air transport network is modeled and constructed as network of Air Route Segment (ARS), which is the minimum unit constituting air routes. Three variations of networks – unweighted, distance-weighted and demand-weighted Air Route Segment Networks (ARSN) are considered. Although not scale-free, the network is more vulnerable to targeted attacks than random failure, with a set of critical nodes identified as ‘pseudo-hubs’. When loss in flight operation is measured in the disrupted network, rerouting improved flight operability significantly. Findings on the set of critical nodes provide key insights for vulnerability of the network, especially in the context of regional coordination against various natural and manmade risks.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Northeast Asian air transport network is modeled as air route segment network. </LI> <LI> Some channeling nodes are identified as ‘pseudo-hubs’ of the regional airspace. </LI> <LI> Critical nodes in demand-weighted network are mostly located in Chinese airspace. </LI> <LI> Critical nodes in distance-weighted network are located in geographical boundary. </LI> <LI> Rerouting greatly improves the loss in flight operations in disrupted networks. </LI> </UL> </P>