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Identification of p54nrb and the 14-3-3 Protein HS1 as TNF-α-Inducible Genes Related to Cell Cycle Control and Apoptosis in Human Arterial Endothelial Cells

  • Stier, Sebastian;Totzke, Gudrun;Grunewald, Elisabeth;Neuhaus, Thomas;Fronhoffs, Stefan;Schoneborn, Silke;Vetter, Hans;Ko, Yon
    • BMB Reports
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    • v.38 no.4
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    • pp.447-456
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    • 2005
  • TNF-$\alpha$ plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-$\alpha$ induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-$\alpha$ on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-$\alpha$ cytotoxicity, presumably by NF-${\kappa}B$ mediated induction of protective genes. However, the cytoprotective genes involved in NF-${\kappa}B$ dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-$\alpha$ inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-$\alpha$-induced expression of the RNA binding protein $p54^{nrb}$ and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-$\alpha$ mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, $p21^{cip1}$ and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-$\alpha$ induced gene expression patterns mediating the prosurvival effect of TNF-$\alpha$ in endothelial cells.

Feasibility Study of Source Position Verification in HDR Brachytherapy Using Scintillating Fiber

  • Moon, Sun Young;Jeong, EunHee;Lim, Young Kyung;Chung, Weon Kyu;Huh, Hyun Do;Kim, Dong Wook;Yoon, Myonggeun
    • Progress in Medical Physics
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    • v.27 no.4
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    • pp.213-219
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    • 2016
  • The position verification of the radiation source utilized in brachytherapy forms a critical factor in determining the therapeutic efficiency. Currently, films are used to verify the source position; however, this method is encumbered by the lengthy time interval required from film scanning to analysis, which makes real-time position verification difficult. In general, the source position accuracy is usually tested in a monthly quality assurance check. In this context, this study investigates the feasibility of the real-time position verification of the radiation source in high dose rate (HDR) brachytherapy with the use of scintillating fibers. To this end, we construct a system consisting of scintillating fibers and a silicon photomultiplier (SiPM), optimize the dosimetric software setup and radiation system characteristics to obtain maximum measurement accuracy, and determine the relative ratio of the measured signals dependent upon the position of the scintillating fiber. According to the dosimetric results based on a treatment plan, in which the dwell time is set at 30 and 60 s at two dwell positions, the number of signals is 31.5 and 83, respectively. In other words, the signal rate roughly doubles in proportion to the dwell time. The source position can also be confirmed at the same time. With further improvements in the spatial resolution and scintillating fiber array, the source position can be verified in real-time in clinical settings with the use of a scintillating fiber-based system.

Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

  • Shin, Kyong-Oh;Park, Nam-Young;Seo, Cho-Hee;Hong, Seon-Pyo;Oh, Ki-Wan;Hong, Jin-Tae;Han, Sang-Kil;Lee, Yong-Moon
    • Biomolecules & Therapeutics
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    • v.20 no.5
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    • pp.470-476
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    • 2012
  • Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

Development of Stakeholder Analysis Framework for Collaborative Tourism development (협력적 관광개발을 위한 이해집단 분석틀 개발에 관한 연구)

  • Shin, Yong-Seok
    • Journal of the Korean Geographical Society
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    • v.44 no.5
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    • pp.647-660
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    • 2009
  • Although tourism has been quite popular as development strategy, the outcomes may vary dependent upon managing stakeholders involved. Thus, stakeholder management has been the subject of growing research interests recently. Collaboration theory was suggested as an alternative to this question; however, collaboration theory may provide potential benefits, it lacks in consideration into stakeholder power relations. The purpose of this paper is two foleded. One is to examine critically collaboration theory in the context of tourism development, and address the necessity of stakeholder analysis framework, and the other is to provide the framework. This paper argues that careful analysis of stakeholders from diverse perspectives should be done in advance, and presents stakeholder analysis framework which consists of six analysis indicators: interest, perspective, power base(resource), involvement, influence, and legitimacy. The framework consists of three stages: (1) identifying stakeholder, (2) assessing stakeholder, and (3) establishing strategies. It is argued that the framework in this paper can be useful to analyze stakeholders and to set up strategy for more collaborative tourism development.

The Introduction of Art Festivals in Small Cities and the Creation of Placeness (소도시의 문화예술축제 도입과 장소성의 인위적 형성)

  • Baik Seonhae
    • Journal of the Korean Geographical Society
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    • v.39 no.6 s.105
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    • pp.888-906
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    • 2004
  • With industrial restructuring and growing competition among places throughout the world, many countries including Korea are getting highly dependent on place marketing as their development strategy. Previous discussions on place marketing strategy maintain that the strategy should be performed on the basis of the unique placeness of each place. Not all places, however, have placeness that can be used for the place marketing strategy. Also, there are some cases of success in place marketing by introducing elements irrelevant to the places. In this context, this study aims to analyze previous debates on place and place marketing, and to investigate the possibility of creating placeness. In addition, it selected as case places the city of Ashland and the city of Jacksonville in the state of Oregon, USA and Tongyeong-si in Korea and examined how the art festivals, one of major means of place marketing, can be used in creating placeness.

Efficient Evaluation of Shared Predicates for XForms Page Access Control (XForms 페이지의 접근제어를 위한 공유 조건식의 효율적 계산 방법)

  • Lee, Eun-Jung
    • The KIPS Transactions:PartD
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    • v.15D no.4
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    • pp.441-450
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    • 2008
  • Recently, access control on form-based web information systems has become one of the useful methods for implementing client systems in a service-oriented architecture. In particular, XForms language is being adopted in many systems as a description language for XML-based user interfaces and server interactions. In this paper, we propose an efficient algorithm for the evaluation of XPath-based access rules for XForms pages. In this model, an XForms page is a sequence of queries and the client system performs user interface realization along with XPath rule evaluations. XPath rules have instance-dependent predicates, which for the most part are shared between rules. For the efficient evaluation of shared predicate expressions in access control rules, we proposed a predicate graph model that reuses the previously evaluated results for the same context node. This approach guarantees that each predicate expression is evaluated for the relevant xml node only once.

Purchase Intention depending on Appraisal of Outward Visual Elements in Superhero Action Figures (슈퍼 히어로 피규어의 외형적 시각요소 평가에 따른 구매의도)

  • Kim, Jun-Su
    • Journal of Digital Contents Society
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    • v.18 no.3
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    • pp.543-550
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    • 2017
  • Superhero films have formed a new genre convention encompassing all the generations. Figures derived from image contents are solid figures produced by means of professional figuration skills. Possession of figures has a symbolic meaning as a medium connecting the imaginary world and real one. From this perspective, figures hold an important position as a character product derived due to market expansion of the content industry. In this context, the study, which analyzed how appraisal of outward visual elements in superhero action figures might affect consumer's purchase intention, aimed to identify their purchase patterns. For this, the study established colors, types of physical body, facial figures and motions as independent variables for appraisal of outward visual elements, and purchase intention as a dependent variable and then conducted a multiple regression analysis. As a result of the analysis, the study found that colors, types of physical body and facial figures had a positive influence on purchase intention, while motions had no significant influence.

Derivation of response spectrum compatible non-stationary stochastic processes relying on Monte Carlo-based peak factor estimation

  • Giaralis, Agathoklis;Spanos, Pol D.
    • Earthquakes and Structures
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    • v.3 no.5
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    • pp.719-747
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    • 2012
  • In this paper a novel approach is proposed to address the problem of deriving non-stationary stochastic processes which are compatible in the mean sense with a given (target) response (uniform hazard) spectrum (UHS) as commonly desired in the aseismic structural design regulated by contemporary codes of practice. The appealing feature of the approach is that it is non-iterative and "one-step". This is accomplished by solving a standard over-determined minimization problem in conjunction with appropriate median peak factors. These factors are determined by a plethora of reported new Monte Carlo studies which on their own possess considerable stochastic dynamics merit. In the proposed approach, generation and treatment of samples of the processes individually on a deterministic basis is not required as is the case with the various "two-step" approaches found in the literature addressing the herein considered task. The applicability and usefulness of the approach is demonstrated by furnishing extensive numerical data associated with the elastic design UHS of the current European (EC8) and the Chinese (GB 50011) aseismic code provisions. Purposely, simple and thus attractive from a practical viewpoint, uniformly modulated processes assuming either the Kanai-Tajimi (K-T) or the Clough-Penzien (C-P) spectral form are employed. The Monte Carlo studies yield damping and duration dependent median peak factor spectra, given in a polynomial form, associated with the first passage problem for UHS compatible K-T and C-P uniformly modulated stochastic processes. Hopefully, the herein derived stochastic processes and median peak factor spectra can be used to facilitate the aseismic design of structures regulated by contemporary code provisions in a Monte Carlo simulation-based or stochastic dynamics-based context of analysis.

Price Escalation Clause of Letter of Credit (신용장의 에스컬레이션 조항)

  • Park, Sae-Woon
    • International Commerce and Information Review
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    • v.16 no.2
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    • pp.89-109
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    • 2014
  • The purpose of price escalation clauses has the effect of increasing the L/C value subject to external pricing mechanisms. This will be found inter alia in metals and oil products transactions. Such a clause gives rise to a question. That is, whether it is enforceable or whether it constitutes a letter of credit. The problem is what to reference to a source outside the context of a letter of credit constitutes a non-documentary condition rendering the undertaking something other than a letter of credit. Reference to an objective and readily available index is not something that renders the undertaking obscure and is not "non-documentary in the sense that it is possible to make an objective verification of the data. The possible solution is that not every non-documentary condition will be disregarded. For example, an index specified in the credit will not be disregarded as stipulated in ISP98 and URDG758. If a non-documentary is "central and fundamental", it seems that the parties intended a dependent payment obligations. The most common means of overcoming this conflicts of interests is to issue an instrument incorporatingan escalation clause, but capping the bank's maximum payment obligation.

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Cytokines Stimulate Lung Epithelial Cells to Release Nitric Oxide

  • Robbins, Richard A.;Kwon, O-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.447-454
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    • 1995
  • Cytokine release from alveolar macrophages and subsequent interaction of these cytokines with the bronchial epithelium can induce epithelial cells to release inflammatory mediators. Nitric oxide(NO), a highly reactive gas formed from arginine by nitric oxide synthase(NOS), is known to be involved in inflammation and edema formation, and the inducible form of NOS(iNOS) can be increased by cytokines. In this context, we hypothesized that lung epithelial cells could be stimulated by cytokines released by alveolar macrophages to express iNOS. To test this hypothesis, the murine lung epithelial cell line, LA-4, or the human lung epithelial cell line, A549, were stimulated with culture supernatant fluids from alveolar macrophages. NO production was assessed by evaluating the culture supernatant fluids for nitrite and nitrate, the stable end products of NO. Both murine and human cell culture supernatant fluids demonstrated an increase in nitrite and nitrate which were time- and dose-dependent and attenuated by $TNF{\alpha}$ and IL-$1{\beta}$ antibodies(p<0.05, all comparisons). Consistent with these observations, cytomix a combination of $TNF{\alpha}$, IL-$1{\beta}$, and $\gamma$-interferon, stimulated the lung epithelial cell lines as well as primary cultures of human bronchial epithelial cells to increase their NO production as evidenced by an increase in nitrite and nitrate in their culture supernatant fluids, an increase in the iNOS staining by immunocytochemistry, and an increase in iNOS mRNA by Northern blottin(p<0.05, all comparisons). The cytokine effects on iNOS were all attenuated by dexamethasone. To determine if these in vitro observations are reflected in vivo, exhaled NO was measured and found to be increased in asthmatics not receiving corticosteroids. These data demonstrate that alveolar macrophage derived cytokines increase iNOS expression in lung epithelial cells and that these in vitro observations are mirrored by increased exhaled NO levels in asthmatics. Increased NO in the lung may contribute to edema formation and airway narrowing.

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