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The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation (Proinflammatory Cytokines과 TGF-beta가 섬유모세포의 증식에 미치는 영향)

  • Kim, Chul;Park, Choon-Sik;Kim, Mi-Ho;Chang, Hun-Soo;Chung, Il-Yup;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yong-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.861-869
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    • 1998
  • Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

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Factors Affecting International Transfer Pricing of Multinational Enterprises in Korea (외국인투자기업의 국제이전가격 결정에 영향을 미치는 환경 및 기업요인)

  • Jun, Tae-Young;Byun, Yong-Hwan
    • Korean small business review
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    • v.31 no.2
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    • pp.85-102
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    • 2009
  • With the continued globalization of world markets, transfer pricing has become one of the dominant sources of controversy in international taxation. Transfer pricing is the process by which a multinational corporation calculates a price for goods and services that are transferred to affiliated entities. Consider a Korean electronic enterprise that buys supplies from its own subsidiary located in China. How much the Korean parent company pays its subsidiary will determine how much profit the Chinese unit reports in local taxes. If the parent company pays above normal market prices, it may appear to have a poor profit, even if the group as a whole shows a respectable profit margin. In this way, transfer prices impact the taxable income reported in each country in which the multinational enterprise operates. It's importance lies in that around 60% of international trade involves transactions between two related parts of multinationals, according to the OECD. Multinational enterprises (hereafter MEs) exert much effort into utilizing organizational advantages to make global investments. MEs wish to minimize their tax burden. So MEs spend a fortune on economists and accountants to justify transfer prices that suit their tax needs. On the contrary, local governments are not prepared to cope with MEs' powerful financial instruments. Tax authorities in each country wish to ensure that the tax base of any ME is divided fairly. Thus, both tax authorities and MEs have a vested interest in the way in which a transfer price is determined, and this is why MEs' international transfer prices are at the center of disputes concerned with taxation. Transfer pricing issues and practices are sometimes difficult to control for regulators because the tax administration does not have enough staffs with the knowledge and resources necessary to understand them. The authors examine transfer pricing practices to provide relevant resources useful in designing tax incentives and regulation schemes for policy makers. This study focuses on identifying the relevant business and environmental factors that could influence the international transfer pricing of MEs. In this perspective, we empirically investigate how the management perception of related variables influences their choice of international transfer pricing methods. We believe that this research is particularly useful in the design of tax policy. Because it can concentrate on a few selected factors in consideration of the limited budget of the tax administration with assistance of this research. Data is composed of questionnaire responses from foreign firms in Korea with investment balances exceeding one million dollars in the end of 2004. We mailed questionnaires to 861 managers in charge of the accounting departments of each company, resulting in 121 valid responses. Seventy six percent of the sample firms are classified as small and medium sized enterprises with assets below 100 billion Korean won. Reviewing transfer pricing methods, cost-based transfer pricing is most popular showing that 60 firms have adopted it. The market-based method is used by 31 firms, and 13 firms have reported the resale-pricing method. Regarding the nationalities of foreign investors, the Japanese and the Americans constitute most of the sample. Logistic regressions have been performed for statistical analysis. The dependent variable is binary in that whether the method of international transfer pricing is a market-based method or a cost-based method. This type of binary classification is founded on the belief that the market-based method is evaluated as the relatively objective way of pricing compared with the cost-based methods. Cost-based pricing is assumed to give mangers flexibility in transfer pricing decisions. Therefore, local regulatory agencies are thought to prefer market-based pricing over cost-based pricing. Independent variables are composed of eight factors such as corporate tax rate, tariffs, relations with local tax authorities, tax audit, equity ratios of local investors, volume of internal trade, sales volume, and product life cycle. The first four variables are included in the model because taxation lies in the center of transfer pricing disputes. So identifying the impact of these variables in Korean business environments is much needed. Equity ratio is included to represent the interest of local partners. Volume of internal trade was sometimes employed in previous research to check the pricing behavior of managers, so we have followed these footsteps in this paper. Product life cycle is used as a surrogate of competition in local markets. Control variables are firm size and nationality of foreign investors. Firm size is controlled using dummy variables in that whether or not the specific firm is small and medium sized. This is because some researchers report that big firms show different behaviors compared with small and medium sized firms in transfer pricing. The other control variable is also expressed in dummy variable showing if the entrepreneur is the American or not. That's because some prior studies conclude that the American management style is different in that they limit branch manger's freedom of decision. Reviewing the statistical results, we have found that managers prefer the cost-based method over the market-based method as the importance of corporate taxes and tariffs increase. This result means that managers need flexibility to lessen the tax burden when they feel taxes are important. They also prefer the cost-based method as the product life cycle matures, which means that they support subsidiaries in local market competition using cost-based transfer pricing. On the contrary, as the relationship with local tax authorities becomes more important, managers prefer the market-based method. That is because market-based pricing is a better way to maintain good relations with the tax officials. Other variables like tax audit, volume of internal transactions, sales volume, and local equity ratio have shown only insignificant influence. Additionally, we have replaced two tax variables(corporate taxes and tariffs) with the data showing top marginal tax rate and mean tariff rates of each country, and have performed another regression to find if we could get different results compared with the former one. As a consequence, we have found something different on the part of mean tariffs, that shows only an insignificant influence on the dependent variable. We guess that each company in the sample pays tariffs with a specific rate applied only for one's own company, which could be located far from mean tariff rates. Therefore we have concluded we need a more detailed data that shows the tariffs of each company if we want to check the role of this variable. Considering that the present paper has heavily relied on questionnaires, an effort to build a reliable data base is needed for enhancing the research reliability.

A Study on the Forest Yield Regulation by Systems Analysis (시스템분석(分析)에 의(依)한 삼림수확조절(森林收穫調節)에 관(關)한 연구(硏究))

  • Cho, Eung-hyouk
    • Korean Journal of Agricultural Science
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    • v.4 no.2
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    • pp.344-390
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    • 1977
  • The purpose of this paper was to schedule optimum cutting strategy which could maximize the total yield under certain restrictions on periodic timber removals and harvest areas from an industrial forest, based on a linear programming technique. Sensitivity of the regulation model to variations in restrictions has also been analyzed to get information on the changes of total yield in the planning period. The regulation procedure has been made on the experimental forest of the Agricultural College of Seoul National University. The forest is composed of 219 cutting units, and characterized by younger age group which is very common in Korea. The planning period is devided into 10 cutting periods of five years each, and cutting is permissible only on the stands of age groups 5-9. It is also assumed in the study that the subsequent forests are established immediately after cutting existing forests, non-stocked forest lands are planted in first cutting period, and established forests are fully stocked until next harvest. All feasible cutting regimes have been defined to each unit depending on their age groups. Total yield (Vi, k) of each regime expected in the planning period has been projected using stand yield tables and forest inventory data, and the regime which gives highest Vi, k has been selected as a optimum cutting regime. After calculating periodic yields and cutting areas, and total yield from the optimum regimes selected without any restrictions, the upper and lower limits of periodic yields(Vj-max, Vj-min) and those of periodic cutting areas (Aj-max, Aj-min) have been decided. The optimum regimes under such restrictions have been selected by linear programming. The results of the study may be summarized as follows:- 1. The fluctuations of periodic harvest yields and areas under cutting regimes selected without restrictions were very great, because of irregular composition of age classes and growing stocks of existing stands. About 68.8 percent of total yield is expected in period 10, while none of yield in periods 6 and 7. 2. After inspection of the above solution, restricted optimum cutting regimes were obtained under the restrictions of Amin=150 ha, Amax=400ha, $Vmin=5,000m^3$ and $Vmax=50,000m^3$, using LP regulation model. As a result, about $50,000m^3$ of stable harvest yield per period and a relatively balanced age group distribution is expected from period 5. In this case, the loss in total yield was about 29 percent of that of unrestricted regimes. 3. Thinning schedule could be easily treated by the model presented in the study, and the thinnings made it possible to select optimum regimes which might be effective for smoothing the wood flows, not to speak of increasing total yield in the planning period. 4. It was known that the stronger the restrictions becomes in the optimum solution the earlier the period comes in which balanced harvest yields and age group distribution can be formed. There was also a tendency in this particular case that the periodic yields were strongly affected by constraints, and the fluctuations of harvest areas depended upon the amount of periodic yields. 5. Because the total yield was decreased at the increasing rate with imposing stronger restrictions, the Joss would be very great where strict sustained yield and normal age group distribution are required in the earlier periods. 6. Total yield under the same restrictions in a period was increased by lowering the felling age and extending the range of cutting age groups. Therefore, it seemed to be advantageous for producing maximum timber yield to adopt wider range of cutting age groups with the lower limit at which the smallest utilization size of timber could be produced. 7. The LP regulation model presented in the study seemed to be useful in the Korean situation from the following point of view: (1) The model can provide forest managers with the solution of where, when, and how much to cut in order to best fulfill the owners objective. (2) Planning is visualized as a continuous process where new strateges are automatically evolved as changes in the forest environment are recognized. (3) The cost (measured as decrease in total yield) of imposing restrictions can be easily evaluated. (4) Thinning schedule can be treated without difficulty. (5) The model can be applied to irregular forests. (6) Traditional regulation methods can be rainforced by the model.

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