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Oxidative Inactivation of Peroxiredoxin Isoforms by H2O2 in Pulmonary Epithelial, Macrophage, and other Cell Lines with their Subsequent Regeneration (폐포상피세포, 대식세포를 비롯한 각종 세포주에서 H2O2에 의한 Peroxiredoxin 동위효소들의 산화에 따른 불활성화와 재생)

  • Oh, Yoon Jung;Kim, Young Sun;Choi, Young In;Shin, Seung Soo;Park, Joo Hun;Choi, Young Hwa;Park, Kwang Joo;Park, Rae Woong;Hwang, Sung Chul
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.1
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    • pp.31-42
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    • 2005
  • Background : Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce $H_2O_2$ and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess $H_2O_2$, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. Methods : This study examined the effect of exogenous, excess $H_2O_2$ on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. Result : The addition of excess $H_2O_2$ to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the $H_2O_2$ treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated $H_2O_2$ treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. Conclusion : The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.

An Empirical Study on Statistical Optimization Model for the Portfolio Construction of Sponsored Search Advertising(SSA) (키워드검색광고 포트폴리오 구성을 위한 통계적 최적화 모델에 대한 실증분석)

  • Yang, Hognkyu;Hong, Juneseok;Kim, Wooju
    • Journal of Intelligence and Information Systems
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    • v.25 no.2
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    • pp.167-194
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    • 2019
  • This research starts from the four basic concepts of incentive incompatibility, limited information, myopia and decision variable which are confronted when making decisions in keyword bidding. In order to make these concept concrete, four framework approaches are designed as follows; Strategic approach for the incentive incompatibility, Statistical approach for the limited information, Alternative optimization for myopia, and New model approach for decision variable. The purpose of this research is to propose the statistical optimization model in constructing the portfolio of Sponsored Search Advertising (SSA) in the Sponsor's perspective through empirical tests which can be used in portfolio decision making. Previous research up to date formulates the CTR estimation model using CPC, Rank, Impression, CVR, etc., individually or collectively as the independent variables. However, many of the variables are not controllable in keyword bidding. Only CPC and Rank can be used as decision variables in the bidding system. Classical SSA model is designed on the basic assumption that the CPC is the decision variable and CTR is the response variable. However, this classical model has so many huddles in the estimation of CTR. The main problem is the uncertainty between CPC and Rank. In keyword bid, CPC is continuously fluctuating even at the same Rank. This uncertainty usually raises questions about the credibility of CTR, along with the practical management problems. Sponsors make decisions in keyword bids under the limited information, and the strategic portfolio approach based on statistical models is necessary. In order to solve the problem in Classical SSA model, the New SSA model frame is designed on the basic assumption that Rank is the decision variable. Rank is proposed as the best decision variable in predicting the CTR in many papers. Further, most of the search engine platforms provide the options and algorithms to make it possible to bid with Rank. Sponsors can participate in the keyword bidding with Rank. Therefore, this paper tries to test the validity of this new SSA model and the applicability to construct the optimal portfolio in keyword bidding. Research process is as follows; In order to perform the optimization analysis in constructing the keyword portfolio under the New SSA model, this study proposes the criteria for categorizing the keywords, selects the representing keywords for each category, shows the non-linearity relationship, screens the scenarios for CTR and CPC estimation, selects the best fit model through Goodness-of-Fit (GOF) test, formulates the optimization models, confirms the Spillover effects, and suggests the modified optimization model reflecting Spillover and some strategic recommendations. Tests of Optimization models using these CTR/CPC estimation models are empirically performed with the objective functions of (1) maximizing CTR (CTR optimization model) and of (2) maximizing expected profit reflecting CVR (namely, CVR optimization model). Both of the CTR and CVR optimization test result show that the suggested SSA model confirms the significant improvements and this model is valid in constructing the keyword portfolio using the CTR/CPC estimation models suggested in this study. However, one critical problem is found in the CVR optimization model. Important keywords are excluded from the keyword portfolio due to the myopia of the immediate low profit at present. In order to solve this problem, Markov Chain analysis is carried out and the concept of Core Transit Keyword (CTK) and Expected Opportunity Profit (EOP) are introduced. The Revised CVR Optimization model is proposed and is tested and shows validity in constructing the portfolio. Strategic guidelines and insights are as follows; Brand keywords are usually dominant in almost every aspects of CTR, CVR, the expected profit, etc. Now, it is found that the Generic keywords are the CTK and have the spillover potentials which might increase consumers awareness and lead them to Brand keyword. That's why the Generic keyword should be focused in the keyword bidding. The contribution of the thesis is to propose the novel SSA model based on Rank as decision variable, to propose to manage the keyword portfolio by categories according to the characteristics of keywords, to propose the statistical modelling and managing based on the Rank in constructing the keyword portfolio, and to perform empirical tests and propose a new strategic guidelines to focus on the CTK and to propose the modified CVR optimization objective function reflecting the spillover effect in stead of the previous expected profit models.