• 한국중재학회지:중재연구
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• 제28권4호
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• pp.173-191
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• 2018

MFN provisions in investment agreements have been a tool for equitable treatment between foreign investors with different nationalities. This non discriminatory principle has been pursued by the host states for further investment promotion. However, it may be abused to bring the situation of so called "ISDS forum shopping" which might harm the stability and predictability of investment agreements by unexpectedly extending the scope of obligations. While some investment arbitral tribunals have interpreted the scope of MFN provision very broadly to allow the ISDS forum shopping, both procedural and substantive provisions have been invoked. To prevent any chaos of unclear boundary of MFN provision, some explicit MFN restrictions which would limit the scope of MFN provision are needed. Indeed, some investment agreements have included these MFN restrictions. Specifically, MFN restrictions deal with both procedural or substantive provisions to prevent ISDS forum shopping. According to the lessons from the recent examples of MFN restrictions, there must be a careful consideration on the benefits and costs of having a certain type of MFN restriction as the parties can be the host state and the home state of their investors at the same time.

• 전자통신동향분석
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• 제15권6호통권66호
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• pp.170-177
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• 2000

GATS의 MFN 원칙은 다자간 협정의 기본초석으로서 협정전체에 적용되기 때문에 양허표에 기재되지 않은 분야라 하더라도 한 국가에게 부여한 대우는 그보다 불리하지 않게 즉시 그리고 무조건적으로 모든 다른 회원국에게 부여해야 한다는 원칙을 가지고 있다. 그러나 이러한 원칙을 모든 나라에게 일률적으로 적용하는 데 현실적으로 어려움이 있다. 따라서 각국별로 MFN 적용이 곤란한 사항에 대하여는 그 내용과 사유, MFN 적용면제기간 등을 기재한 목록을 제출하여 MFN 면제를 인정받게 되었다. 그러나 이러한 GATS MFN 면제규정은 일반적 의무로서 MFN 원칙의 가치를 상당히 침해하였고, 현재 많은 국가가 MFN 면제신청을 하므로써 GATS가 처음 의도한 MFN과 상당한 괴리를 보이게 되었다. 따라서 본 고에서는 GATS의 MFN에 관하여 살펴보고, MFN 면제의 문제점 및 정책적 시사점을 모색해 보았다.

• 무역학회지
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• 제42권4호
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• pp.139-157
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• 2017

투자협정상의 MFN 조항을 실체적인 규정 외에 절차적인 규정에까지 적용할 수 있는지에 대한 논의는 보호 범위를 결정하기 때문에 중요한 의의를 가진다. 그러나 투자협정마다 MFN 조항에서 대우의 범위를 조금씩 상이하게 규정하고 있어 이에 대한 해석의 차이가 존재한다. 그러므로 본 연구는 ICSID에서 판정한 중재사례에 초점을 맞추어 국제투자분쟁에서 외국인투자자가 원 투자협정상의 MFN 조항을 통하여 다른 투자협정상에 규정된 분쟁해결절차를 원용할 수 있는지를 분석함으로써 MFN 조항의 적용범위를 획정할 수 있는 기준들을 도출하여 유용한 시사점 및 실무적인 지침을 제시하고자 한다.

• BMB Reports
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• 제57권4호
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• pp.194-199
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• 2024

Overexpression of mitofusin-2 (MFN2), a mitochondrial fusion protein, is frequently associated with poor prognosis in cervical cancer patients. Here, I aimed to investigate the involvement of MFN2 in cervical cancer progression and determine the effect of MFN2 on prognosis in cervical cancer patients. After generating MFN2-knockdown SiHa cells derived from squamous cell carcinoma, I investigated the effect of MFN2 on SiHa cell proliferation using the Cell Counting Kit-8 assay and determined the mRNA levels of proliferation markers. Colony-forming ability and tumorigenesis were evaluated using a colony-formation assay and tumor xenograft mouse models. The migratory and invasive abilities associated with MFN2 were measured using wound-healing and invasion assays. Wnt/β-catenin-mediated epithelial-mesenchymal transition (EMT) markers related to MFN2 were assessed through quantitative RT-PCR. MFN2-knockdown SiHa cells exhibited reduced proliferation, colony formation, migration, invasion, and tumor formation in vivo. The motility of SiHa cells with MFN2 knockdown was reduced through Wnt/β-catenin-mediated EMT inhibition. MFN2 promoted cancer progression and tumorigenesis in SiHa cells. Overall, MFN2 could serve as a therapeutic target and a novel biomarker for cervical cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.71-77
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• 2012

Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal ${\beta}$-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

• IMMUNE NETWORK
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• 제21권4호
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• pp.30.1-30.12
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• 2021

High expression of mitofusin-2 (MFN2), a mitochondrial fusion protein, has been frequently associated with poor prognosis of patients with cervical cancer. Here, we aimed to identify the function of MFN2 in cervical cancer to understand its influence on disease prognosis. To this end, from cervical adenocarcinoma, we performed an MTT assay and quantitative RT-PCR (qRT-PCR) analysis to assess the effects of MFN2 on the proliferation and of HeLa cells. Then, colony-formation ability and tumorigenesis were evaluated using a tumor xenograft mouse model. The migration ability related to MFN2 was also measured using a wound healing assay. Consequently, epithelial-mesenchymal transition (EMT) of MFN2-knockdowned HeLa cells originating from adenocarcinoma. markers related to MFN2 were assessed by qRT-PCR. Clinical data were analyzed using cBioPortal and The Cancer Genome Atlas. We found that MFN2 knockdown reduced the proliferation, colony formation ability, migration, and in vivo tumorigenesis of HeLa cells. Primarily, migration of MFN2-knockdowned HeLa cells decreased through the suppression of EMT. Thus, we concluded that MFN2 facilitates cancer progression and in vivo tumorigenesis in HeLa cells. These findings suggest that MFN2 could be a novel target to regulate the EMT program and tumorigenic potential in HeLa cells and might serve as a therapeutic target for cervical cancer. Taken together, this study is expected to contribute to the treatment of patients with cervical cancer.

• Annals of Clinical Neurophysiology
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• 제21권1호
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• pp.57-60
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• 2019

Axonal Charcot-Marie-Tooth disease (CMT2) has most frequently been associated with mutations in the MFN2 gene. MFN2 encodes mitofusin 2, which is a mitochondrial fusion protein that plays an essential role in mitochondrial function. We report CMT2 in a Korean father and his son that manifested with gait difficulties and progressive atrophy of the lower legs. Molecular analysis revealed a novel heterozygous c.2096T>C (p.Leu699Pro) mutation in the exon 18 of MFN2 in both subjects. We suggest that this novel mutation in MFN2 is probably a pathogenic mutation for CMT2.

• Journal of Korea Trade
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• 제24권2호
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• pp.15-30
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• 2020

Purpose - This paper investigates the theories and practices of Most-Favored-Nation (MFN) clauses. The MFN clause became a controversial issue during the past two decades, especially in the context of investment arbitration. This paper aims to clarify a reasonable way to apply MFN clauses. It in particular focuses on the territoriality requirements and the scope of investment activity which are common features included in most of investment treaties. Design/methodology - This paper analyses two investment arbitration cases, Ansung Housing and Beijing Urban Construction. Through the case study, this paper reveals limitations of the currently dominant views on the operation of MFN clauses. It then tries to reconstruct the system of MFN application within the relevant arbitration principles. Findings - Tribunals of recent investment arbitration as represented in the two cases above employed strict literal interpretation of the treaty provisions, especially of the phrase "in its territory". This paper finds a more functional interpretation is appropriate and consistent with theories of public international law and developments of global economy. Originality/value - Existing studies either stuck to literal interpretation or suggested more flexible interpretation of the phrase "in its territory" without full explanation. This paper tries to fill the gap in the existing discussion by analyzing legal foundations and theoretical structure for an effective interpretation of MFN clauses.

• Molecules and Cells
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• 제38권1호
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• pp.89-94
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• 2015

The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration. These results suggest that the mitochondrial fusion-related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.

• 한국중재학회지:중재연구
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• 제20권1호
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• pp.109-131
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• 2010

Investment Agreement is to be a part of FTA, as negotiating together both trade and investment. For example, it has a separate chapter about investment in KORUS FTA contract and is more detailed and inclusive than BIT contents which are traditional investment provisions. It is called to the investment norm of FT A. The investment agreement lures a foreign investment by providing the environment which is stable to the foreign investors. Hence, it plans in goal for the economic development of the home country. In international investment, the arbitration award cases are coming out to be divided into two parts applying MFN provisions in investor protective principles and dispute resolution process; the tendency of broad interpretation and the tendency of limited interpretation. In the case of RosInvest Co UK Ltd v. the Russian Federation awarded in 2007, the arbitration tribunal interprets that the application scope of MFN provisions contain the more lucrative dispute provision than other BITs without limitations in entity right of the investor. This judgment is the same view as arbitration tribunal position of Maffezini case. The arbitration tribunal of Plama case has kept out an assertion magnifying the arbitration tribunal's jurisdiction. That is, for applying more inclusive investor-nation resolution method from different treaty, tribunal mentioned that MFN provision had to see clearly a point of applying the investor-nation dispute resolution method. Dispute resolution process providing inclusive MFN provision has both the tendency of broad interpretation and the tendency of limited interpretation. It needs ceaselessly to do the monitoring about cases of arbitration award. In conclusion, the point where MFN provisions are applied conclusively is recognized, but it is still controversial whether or not to magnify the jurisdiction of arbitration tribunal applying MFN provisions. Therefore, it does not exist clear principle in the theory or in the award eases about the application scope for entity protection provision of MFN. Hence, The Korean government of Korea and local autonomous entities needs to keep their eyes on the trend of the international arbitration award cases in relation to the investment dispute for the future. Also, Korean government or local self-governing group must consider MFN provisions when they make a contract of international investment treaty such as writing concretely the application of MFN provisions from KORUS FTA.