• Title/Summary/Keyword: Mode of action

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Purification and Properties of ${\beta}-Mannanases$ from Germinated Guar Bean (${\beta}-Mannanase$ 군(群)의 정제(精製) 및 그들의 성질(性質)에 관(關)한 연구(硏究))

  • Lee, Su-Rae
    • Applied Biological Chemistry
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    • v.7
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    • pp.1-13
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    • 1966
  • 1) Three ${\beta}-1$, 4-mannanases were isolated from germinated guar bean through extraction, ammonium sulfate fractionation, column chromatography on cellulose derivatives and gel filltration on Sephadex G-100. They were designated as ${\beta}-1$, 4-mannanase A,B and C, respectively, in the order of isolation. 2) These enzymes were different in several aspects such as pH optimum, effect of metal ions, adsorbability on cellulose derivatives, molecular weight, Michaelis constant toward reduced ivory nut mannan A, mode of action and extent of hydrolysis of the mannan. 3) ${\beta}-1$, 4-Mannanases A and C were proposed to be two different endo-enzymes of random-splitting type producing a series of oligosaccharides from ${\beta}-1$, 4-mannans. ${\beta}-1$, 4-Mannanase B was suggested to be possibly an exe-type enzyme catalyzing a stepwise splitting from the non-reducing end of ${\beta}-1$, 4-mannans to produce mannose. 4) Guaran was subjected to hydrolysis by the purified enzymes and the consequence was discussed in connection with structural requirements of the enzymes toward substituted ${\beta}-1$, 4-mannans and their role in germinating guar seeds.

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Anti-diabetic peptides derived from milk proteins (우유단백질 유래 혈당 조절 기능성 펩타이드)

  • Kim, Seonyoung;Imm, Jee-Young
    • Food Science and Industry
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    • v.51 no.4
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    • pp.302-312
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    • 2018
  • Bioactive peptides generated from milk proteins play an important role in the prevention and alleviation of diabetes. Whey proteins possess direct insulinotropic effect by amino acids (especially branch chain amino acids) produced through its gastrointestinal digestion. Additionally, blood glucose level can be lowered by gut hormone which called incretin [glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]. However, physiological effects of incretin readily disappeared by dipeptidyl peptidase-4 (DPP-4) causing degradation of GLP-1. Several DPP-4 inhibitors are currently used as therapeutic medicines for the treatment of type II diabetes. More than 60 natural peptide (2-14 amino acids) DPP-4 inhibitors were identified in milk proteins. Peptide DPP-4 inhibitors act as substrate inhibitor and delay breakdown of GLP-1 both in vitro and in vivo. This review summarizes nutritional quality of milk proteins, absorption and mode of action of bioactive peptides, and finally up-to-dated knowledge on DPP-4 inhibitory peptides derived from milk proteins.

Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Analysis of Aircraft Upset through TEM and Improvement of UPRT (항공기 비정상 자세 사고의 TEM 분류 및 UPRT 향상에 관한 연구)

  • Choi, Jin-Kook;Jeon, Seung-Joon
    • The Journal of the Korea Contents Association
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    • v.19 no.11
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    • pp.365-374
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    • 2019
  • Loss of Control in Flight(LOC-I) due to aircraft upset attitude has the highest air accident rate, and International Aviation Institute such as ICAO and FAA recommended flight crew to operate aircraft safely through UPRT(Upset Prevention & Recovery Training) program. ICAO has selected Loss of Control(LOC) as key safety indicator, and recommended to respond using TEM(Threat and Error Management). However there are not much specific treats and errors classified for UPRT programs using real TEM based on evidences. This study intends to consider the importance of UPRT through the introduction of UPRT and accident analysis using TEM. Typical upset accidents were classified to common threats as IFR, inadequate training, Automation surprise, and inexperienced copilots. The common errors were cross-check, speed and altitude deviation, callouts, communication, thrust and stall action fail. The undesired aircraft states were inadequate automation mode, Deviation of speed and vertical, stall, and crash. These suggest areas to improve UPRT.

Insect Juvenile Hormone Antagonists as Eco-friendly Insecticides (친환경 살충제로서의 곤충 유충호르몬 길항제)

  • Choi, Jae Young;Je, Yeon Ho
    • Korean journal of applied entomology
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    • v.61 no.1
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    • pp.101-108
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    • 2022
  • Because of their specificity to target insects and relatively low toxicity to non-target organisms, insect growth regulators (IGRs) have been regarded as attractive alternatives to chemical insecticides. Commercially available IGRs are classified into juvenile hormone agonists (JHAs), ecdysone agonists (EAs), and chitin synthesis inhibitors (CSIs) according to their mode of action. Recently, JH-mediated interaction of methoprene-tolerant (Met), which is JH receptor, and its binding partners have been replicated in vitro using yeast cells transformed with the Met and FISC/CYC genes of A. aegypti. Using this in vitro yeast two-hybrid β-galactosidase assay, juvenile hormone antagonists (JHANs) have been identified from various sources including chemical libraries, plants, and microorganisms. As juvenile hormone (JH) is an insect specific hormone and regulates development, reproduction, diapause and other physiological processes, JHANs fatally disrupt the endocrine signals, which result in abnormal development and larval death. These results suggested that JHANs could be efficiently applied as IGR insecticides with a broad insecticidal spectrum. This review discuses JH signaling pathway mediated by Met and future prospects of JHANs as environmentally benign IGR insecticides.

The role of $Na^+-Ca^{2+}$ exchange on calcium activated chloride current in single isolated cardiac myocyte in pulmonary vein of rabbit.

  • Kim, Won-Tae;Lee, Yoon-Jin;Ha, Jeong-Mi;Han Choe;Jang, Yeon-Jin;Park, Chun-Sik;Lee, Chae-Hun m
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.37-37
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    • 2003
  • We have shown the $Ca^{2+}$-activated chloride current is present in cardiac myocyte in rabbit pulmonary vein (Kim et al., 2002). This current amplitude was increased as [N $a^{+}$]$_{i}$ was increased and we suggested this chloride current may be involve in the spontaneous action potential frequency change. Since this current is activated by the increase of intracellular $Ca^{2+}$, we would like to test what is the inducer of the increase of [C $a^{2+}$]$_{i}$ between a L-type $Ca^{2+}$-current or a reverse mode of N $a^{+}$-C $a^{2+}$ exchange current. White rabbit (1.5 kg) was used and anesthetized with Ketamin (100 mg/kg). Pulmonary vein (PV) was isolated and sleeve area between left atrium and PV was dissected. Using collagenase (Worthington 0.7 mg/cc), single cardiac myocytes were isolated. In the presence of 15 mM of N $a^{+}$, three steps of voltage pulses were applied (holding potential : -40 ㎷, -80 ㎷ for 50 msec, 30 ㎷ for 5 msec, 10 ㎷ steps from -70 ㎷ to 60 ㎷). The inward and outward tail current was activated after brief 5 msec prepulse. The outward tail current was blocked by the removal of extracellular chloride substituted by glucuronic acid or by a chloride channel blocker, 5 mM 9-AC. But the inward tail current was still remained even though the amplitude was decreased. The reversal potentials were changed to the direction of the change of chloride equilibrium potential ( $E_{Cl}$ ) but the shift of equilibrium potential was not enough to match to the theoretical equilibrium potential shift. In the presence of L-type $Ca^{2+}$ channel blocker, nifedipine 1 uM, inward tail currents were greatly reduced but the outward current tail currents were still remained. In the presence of N $a^{+}$-C $a^{2+}$ exchange current blocker, 10 uM KB-R7943, the inward and outward tail currents were blocked almost completely. We tried to test the $Ca^{2+}$sensitivity of the chloride current with various [C $a^{2+}$]$_{i}$ in pipette solution from 100 nM to 1 uM but we failed to activate $Ca^{2+}$-activated chloride currents even though the cell became contracted in the presence of 1 uM $Ca^{2+}$. From these results, we could conclude that the increase of [C $a^{2+}$]$_{i}$ to activate the outward $Ca^{2+}$-activated chloride current was mainly induced by the activation of the reverse mode of N $a^{+}$-C $a^{2+}$ exchanger, But for the increase of [C $a^{2+}$]$_{i}$ to activate the inward tail current, L-type $Ca^{2+}$ current may be the major provoking current. Since the cytosolic increase of [C $a^{2+}$]$_{i}$ through pipette solution have failed to activate $Ca^{2+}$-activated chloride current, this chloride current may have very low $Ca^{2+}$ sensitivity or a comparmental increase $Ca^{2+}$ such as in subsarcolemmal space may activate the chloride current. Since there are several reports and models that the increase of $Ca^{2+}$ in subsarcolemmal space would be over several to tens of uM, both possibility may be valid together.uM, both possibility may be valid together.

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Roles of the Insulin-like Growth Factor System in the Reproductive Function;Uterine Connection (Insulin-like Growth Factor Systems의 생식기능에서의 역할;자궁편)

  • Lee, Chul-Young
    • Clinical and Experimental Reproductive Medicine
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    • v.23 no.3
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    • pp.247-268
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    • 1996
  • It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

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Occurrence and Deformation of Fe-Ti ores from the Proterozoic Hadong Anorthosites, Korea (원생대 하동회장암체 내 철-티탄 광체의 산상과 변형)

  • Jung, Jae-Sung;Kim, Jong-Sun;Cho, Hyeong-Seong;Song, Cheol-Woo;Son, Moon;Ryoo, Chung-Ryul;Chi, Sei-Jeong;Kim, In-Soo
    • The Journal of the Petrological Society of Korea
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    • v.19 no.1
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    • pp.31-49
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    • 2010
  • Nearly NS-trending Fe-Ti ore bodies intermittently occur in the Hadong anorthosites, south Korea, irrespective of the rock types of the anorthosites. In order to determine their occurrence mode and deformation history, we collected the features of occurrence and geological structures in the field, petrographic features using thin sections of the principal constituent rocks, and geochemical data of ilmenites in the ore body using electron probe microanalysis. Fe-Ti ore bodies examined in this study are divided into two types: dike- and lamina-types. It is steadily supported that the dike-type has intruded into the anorthositic rocks after their emplacement and solidification. And the laminar-type is probably a result of the mylonitization and transposition of the dike-type ore bodies parallel to the shear planes, due to later strong dextral ductile shearing. In the meantime, the Fe-Ti ore bodies have experienced the stronger dextral shearing in the more northern part of the study area, i.e. Cheongryong-ri, Wolhoeng-ri, Jonghwa-ri, and Jayangri and Baekun-ri in ascending order of its strength, together with the less content of $TiO_2$. All ilmenites of the ore bodies have very similar chemical composition, as pure ilmenite of 52~55 wt.% in $TiO_2$ content, irrespective of the occurrence mode and degree of later ductile shearing of the ore bodies. And they didn't experience to exsolve into magnetite. The structural data indicate that the Hadong anorthosites have deformed by NNE-trending folding, intrusion of the Fe-Ti ore bodies, NNW~NNE-trending dextral ductile shearing, NW~NNW-trending sinistral semi-brittle shearing, and intrusion of NNE~NE-trending mafic dykes in descending order of chronology after the formation of foliation of the anorthositic rocks. The foliation is interpreted as a result of the accumulation of crystals that settle out from the magma by the action of gravity.

The Influence of 5-Fluorouracil Administration Mode on the Expression of Phospholipase C and Ras Oncoprotein Associated with Regeneration of Rat Intestinal Mucosa Following Radiation (방사선 조사후 백서 공장 점막의 재생과정에서 5-fluorouracil 투여가 phospholipsse C 와 ras 암유전자단백의 발현에 미치는 영향)

  • Park Kyung Ran;Lee Chung Sik;Kim Sung Sook;Lee Young Han;Ryu Sung Ho;Suh Pann-Ghill
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.271-284
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    • 1994
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in transmembrane signal transduction. PLC-${\gamma}1$ acts as the intracellular effector in signal transduction for cellular proliferation and differentiation. Ras oncoprotein is also involved in cell growth. We determined the biological significance of PLC and ras oncoprotein in regeneration following radiation and the effect of different modes of administration of 5-FU. Materials and Methods : To determine the effect of the administration mode of 5-FU on the regeneration of intestinal mucosa of rats following radiation, we compared the expression of PLC and ras oncoprotein in six groups. Group I had no treatment. Group II received radiation(8 Gy) only. Group III received radiation(8 Gy) and 5-FU(150mg/kg) continuous intravenous (iv) infusion for 12 hours. Group IV received radiation(8 Gy) and 5-FU(750mg/kg) iv bolus injection. Group V received only 5-FU(150mg/kg) continuous iv infusion for 12 hours, Group VI received only 5-FU (150mg/kg) iv bolus injection. Through immunoblotting and immunohistochemistry, we examined the expression of PLC and ras oncoprotein in rat jejunum at 96 hours after radiation or 5-FU administration and at 120 hours after radiation and 5-FU adminstration. We also investigated the histological findings using hematoxylin and eosin stain. Results : In the immunohistochemistry study, PLC-${\gamma}1$ expression was the highest in group III followed by groups II and VI in that order and was weakly positive in groups V and VI. PLC-${\gamma}1$ was hardly detected in the control group. The expression of ras oncoprotein was the same as the PLC-${\gamma}1$ expression for all groups. These results were confirmed by the histological findings regarding the mucosal regeneration. In the immunoblotting analysis, PLC-${\gamma}1$ expression was the highest in group III followed by group IV and II in that order. This difference between the immunoblotting and immunohistochemistry study was due to the high expression of PLC-${\gamma}1$ on the damaged surface epithelium rather than to its expression in the regeneration region as observed in the immunohistochemistry study for group IV. The expression of PLC-${\delta}1$ was positive only in group V and VI, which received both radiation and 5-FU, and the expression of PLC-${\beta}1$ was negligible for all groups. Conclusion : These results suggest that PLC-${\gamma}1$ mediated signal transduetion and ras oncoprotein may have a significant role in mucosal regeneration after radiation, and that continuous iv infusion of 5-FU may induce active regeneration in intestinal mucosa following radiation. In addition, the expression of PLC-${\delta}1$ in combined group of radiation and 5-FU implies that PLC-${\delta}1$ may be involved in signal transduction mediated by concerted action between radiation and 5-FU.

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The International Civil Aviation Organization and Recent Developments of Air Law in a Changing Environment (변환기(變換期)에 있어서의 국제민간항공기구(國際民間航空機構)(ICAD)와 항공법(航空法) 발전(發展)의 최근(最近) 동향(動向))

  • Choi, Wan-Sik
    • The Korean Journal of Air & Space Law and Policy
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    • v.4
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    • pp.7-35
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    • 1992
  • The expansion of air transport on a global scale with ever increasing traffic densities has brought about problems that must be solved through new multilateral mechanisms. Looking to the immediate future, air transport will require new forms of international cooperation in technical and economic areas. Air transport by its very nature should have been a counterforce to nationalism. Yet, the regulatory system in civil aviation is still as firmly rooted in the principle of national sovereignty as when it was first proclaimed at t-11e Paris Convention of 1919 and reaffirmed in the Chicago Convention. Sovereignty over the airspace has remained the cornerstone of relations between states in all respects of air transport. The importance of sovereignty over air space embodied in article 1 of the Chicago Conrenton also is responsible for restricting the authority of ICAO as an intergovernmental regulatory agency. The Orgenization, for all its extensive efforts, has only limited authority. ICAO sets standards but cannot enforce them; it devises solutions but cannot impose them. To implement its rules ICAO most rely not so much on legal requirements as on the goodwill of states. It has been forty-eight years since international community set the foundations of the international system in civil aviation action. Profound political, economic and technological changes have taken place in air transport. The Chicago Convention is living proof that staes can work together to make air transport a safe mode of travel. The law governing international civil auiation is principally based on international treaties and on other regulation agreed to by governments, for the most part through the mechanism of ICAO. The role of ICAO international standards and recommended practices and procedures dealing with a broad range of technical matters could hardly be overestimated. The organization's ability to develop these standards and procedures, to adapt them continuously to the rapid sate of change and development of air transport, should be particularly stressed. The role of ICAO in the area of the development of multilateral conventions on international air law has been successful but to a certain degree. From the modest starting-point of the Tokyo Convention, we have seen more adequate international instruments prepared within the scope of ICAO activities, adopted: the Hague Convention of 1970 for the suppression of Unlawful Seizure of Aircraft and the Montreal Convention of 1971 for the Suppression of Unlawful Acts against the Safety of Civil Aviation. The work of ICAO in the new domain of international law conventions concerning what has been loosely termed above as the criminal problems connected with international air transport, in particular the problem of armed aggression against aircraft, should be positively appreciated. But ICAO records in the domain of developing a uniform legal system of international carriage by air are rather disappointing. The problem of maintaining and developing the uniformity of this regulation exceeds the scope of interest and competence of governmental transport agencies. The expectations of mankind linked to it are too great to give up trying to restore the uniform legal system of international air carriage that would create proper conditions for its further growth. It appears that ICAO has, at present, a good opportunity for doing this. The hasty preparation of ICAO draft conventions should be definitely excluded. Every Preliminary draft convention ought to be sent to Governments of all member-States for consideration, So that they could in form ICAO in due time of their observation. The problom of harmonizing a uniform law of international air carriage with that of other branches of international transport should demand more and more of its attention. ICAO cooperation with other international arganization, especially these working in the field of international transport, should be strengthened. ICAO is supposed to act as a link and a mediator among, at times the conflicting interests of member States, serving the happiness and peace of all of the world. The transformation of the contemporary world of developing international relations, stimulated by steadily growing international cooperation in its various dimensions, political, economic, scientific, technological, social and cultural, continuously confronts ICAO with new task.

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