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Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK (담배 연기에 의한 Muc5ac 유전자 발현에 관여하는 세포 내 신호 전달 경로로서의 ERK1/2와 p38 MAPK)

  • Kim, Yong Hyun;Yoon, Hyoung Kyu;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup;Cho, Kyung Sook
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.6
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    • pp.590-599
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    • 2005
  • Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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Effects of firm strategies on customer acquisition of Software as a Service (SaaS) providers: A mediating and moderating role of SaaS technology maturity (SaaS 기업의 차별화 및 가격전략이 고객획득성과에 미치는 영향: SaaS 기술성숙도 수준의 매개효과 및 조절효과를 중심으로)

  • Chae, SeongWook;Park, Sungbum
    • Journal of Intelligence and Information Systems
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    • v.20 no.3
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    • pp.151-171
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    • 2014
  • Firms today have sought management effectiveness and efficiency utilizing information technologies (IT). Numerous firms are outsourcing specific information systems functions to cope with their short of information resources or IT experts, or to reduce their capital cost. Recently, Software-as-a-Service (SaaS) as a new type of information system has become one of the powerful outsourcing alternatives. SaaS is software deployed as a hosted and accessed over the internet. It is regarded as the idea of on-demand, pay-per-use, and utility computing and is now being applied to support the core competencies of clients in areas ranging from the individual productivity area to the vertical industry and e-commerce area. In this study, therefore, we seek to quantify the value that SaaS has on business performance by examining the relationships among firm strategies, SaaS technology maturity, and business performance of SaaS providers. We begin by drawing from prior literature on SaaS, technology maturity and firm strategy. SaaS technology maturity is classified into three different phases such as application service providing (ASP), Web-native application, and Web-service application. Firm strategies are manipulated by the low-cost strategy and differentiation strategy. Finally, we considered customer acquisition as a business performance. In this sense, specific objectives of this study are as follows. First, we examine the relationships between customer acquisition performance and both low-cost strategy and differentiation strategy of SaaS providers. Secondly, we investigate the mediating and moderating effects of SaaS technology maturity on those relationships. For this purpose, study collects data from the SaaS providers, and their line of applications registered in the database in CNK (Commerce net Korea) in Korea using a questionnaire method by the professional research institution. The unit of analysis in this study is the SBUs (strategic business unit) in the software provider. A total of 199 SBUs is used for analyzing and testing our hypotheses. With regards to the measurement of firm strategy, we take three measurement items for differentiation strategy such as the application uniqueness (referring an application aims to differentiate within just one or a small number of target industry), supply channel diversification (regarding whether SaaS vendor had diversified supply chain) as well as the number of specialized expertise and take two items for low cost strategy like subscription fee and initial set-up fee. We employ a hierarchical regression analysis technique for testing moderation effects of SaaS technology maturity and follow the Baron and Kenny's procedure for determining if firm strategies affect customer acquisition through technology maturity. Empirical results revealed that, firstly, when differentiation strategy is applied to attain business performance like customer acquisition, the effects of the strategy is moderated by the technology maturity level of SaaS providers. In other words, securing higher level of SaaS technology maturity is essential for higher business performance. For instance, given that firms implement application uniqueness or a distribution channel diversification as a differentiation strategy, they can acquire more customers when their level of SaaS technology maturity is higher rather than lower. Secondly, results indicate that pursuing differentiation strategy or low cost strategy effectively works for SaaS providers' obtaining customer, which means that continuously differentiating their service from others or making their service fee (subscription fee or initial set-up fee) lower are helpful for their business success in terms of acquiring their customers. Lastly, results show that the level of SaaS technology maturity mediates the relationships between low cost strategy and customer acquisition. That is, based on our research design, customers usually perceive the real value of the low subscription fee or initial set-up fee only through the SaaS service provide by vender and, in turn, this will affect their decision making whether subscribe or not.

Semiweekly variation of Spring Phytoplankton Community in Relation to the Freshwater Discharges from Keum River Estuarine Weir, Korea (금강하구언 담수방류와 춘계 식물플랑크톤 군집의 단주기 변동)

  • Yih, Won-Ho;Myung, Geum-Og;Yoo, Yeong-Du;Kim, Young-Geel;Jeong, Hae-Jm
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.10 no.3
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    • pp.154-163
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    • 2005
  • Irregular discharges of freshwater through the water gates of the Keum River Estuarine Weir, Korea, whose construction had been completed in 1998 with its water gates being operated as late as August 1994, drastically modified the estuarine environment. Sharp decrease of salinity along with the altered concentrations of inorganic nutrients are accompanied with the irregular discharges of freshwater into the estuary under the influence of regular semi-diurnal tidal effect. Field sampling was carried out on the time of high tide at 2 fixed stations(St.1 near the Estuarine Weir and St.2 off Kunsan Ferry Station) every other day for 4 months from mid-February 2004 to investigate into the semi-weekly variation of spring phytoplankton community in relation to the freshwater discharges from Keum River Estuarine Weir. CV(coefficient of variation) of salinity measurements was roughly 2 times greater in St.1 than that in St.2, reflecting extreme salinity variation in St.1 Among inorganic nutrients, concentrations of N-nutrients($NO_3^-,\;NO_2^-$ and $NH_4^+$) were clearly higher in St.1, to imply the more drastic changes of the nutrient concentrations in St.1. than St.2 following the freshwater discharges. As a component of phytoplankton community, diatoms were among the top dominants in terms of species richness as well as biomass. Solitary centric diatom, Cyclotella meneghiniana, and chain-forming centric diatom, Skeletonema costatum, dominated over the phytoplankton community in order for S-6 weeks each (Succession Interval I and II), and the latter succeeded to the former from the time of <$10^{\circ}C$ of water temperature. Cyanobacterial species, Aphanizomenon Posaquae and Phormidium sp., which might be transported into the estuary along with the discharged freshwater, occupied high portion of total biomass during Succession Interval III(mid-April to late-May). During this period, freshwater species exclusively dominated over the phytoplankton community except the low concentrations of the co-occurring 2 estuarine diatoms, Cyclotella meneghiniana and Skeletonema costatum. During the 4th Succession Interval when the water temperature was over $18^{\circ}C$, the diatom, Guinardia delicatula, was predominant for a week with the highest dominance of $75\%$ in discrete samples. To summarize, during all the Succession Intervals other than Succession Interval III characterized by the extreme variation of salinity under cooler water temperature than $18^{\circ}C$, the diatoms were the most important dominants for species succession in spring. If the scale and frequency of the freshwater discharge could have been adjusted properly even during the Succession Interval III, the dominant species would quite possibly be replaced by other estuarine diatom species rather than the two freshwater cyanobacteria, Aphanizomenon flosaquae and Phormidium sp.. The scheme of field sampling every other day for the present study was concluded to be the minimal requirement in order to adequately explore the phytoplankton succession in such estuarine environment as in Keum River Estuary: which is stressed by the unpredictable and unavoidable discharges of freshwater under the regular semi-diurnal tide.

Roles and Preparation for the Future Nurse-Educators (미래 간호교육자의 역할과 이를 위한 준비)

  • Kim Susie
    • The Korean Nurse
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    • v.20 no.4 s.112
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    • pp.39-49
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    • 1981
  • 기존 간호 영역 내 간호는 질적으로, 양적으로 급격히 팽창 확대되어 가고 있다. 많은 나라에서 건강관리체계가 부적절하게 분배되어 있으며 따라서 많은 사람들이 적절한 건강관리를 제공받지 못하고 있어 수준 높은 양질의 건강관리를 전체적으로 확대시키는 것이 시급하다. 혹 건강관리의 혜택을 받는다고 해도 이들 역시 보다 더 양질의 인간적인 간호를 요하고 있는 실정이다. 간호는 또한 간호영역 자체 내에서도 급격히 확대되어가고 있다. 예를들면, 미국같은 선진국가의 건강간호사(Nurse practitioner)는 간호전문직의 새로운 직종으로 건강관리체계에서 독자적인 실무자로 그 두각을 나타내고 있다. 의사의 심한 부족난으로 고심하는 발전도상에 있는 나라들에서는 간호원들에게 전통적인 간호기능 뿐 아니라 건강관리체계에서 보다 많은 역할을 수행하도록 기대하며 일선지방의 건강센터(Health center) 직종에 많은 간호원을 투입하고 있다. 가령 우리 한국정부에서 최근에 시도한 무의촌지역에서 졸업간호원들이 건강관리를 제공할 수 있도록 한 법적 조치는 이러한 구체적인 예라고 할 수 있다. 기존 간호영역내외의 이런 급격한 변화는 Melvin Toffler가 말한 대로 ''미래의 충격''을 초래하게 되었다. 따라서 이러한 역동적인 변화는 간호전문직에 대하여 몇가지 질문을 던져준다. 첫째, 미래사회에서 간호영역의 특성은 무엇인가? 둘째, 이러한 새로운 영역에서 요구되는 간호원을 길러내기 위해 간호교육자는 어떤 역할을 수행해야 하는가? 셋째 내일의 간호원을 양성하는 간호교육자를 준비시키기 위한 실질적이면서도 현실적인 전략은 무엇인가 등이다. 1. 미래사회에서 간호영역의 특성은 무엇인가? 미래의 간호원은 다음에 열거하는 여러가지 요인으로 인하여 지금까지의 것과는 판이한 환경에서 일하게 될 것이다. 1) 건강관리를 제공하는 과정에서 컴퓨터화되고 자동화된 기계 및 기구 등 새로운 기술을 많이 사용할 것이다. 2) 1차건강관리가 대부분 간호원에 의해 제공될 것이다. 3) 내일의 건강관리는 소비자 주축의 것이 될 것이다. 4) 간호영역내에 많은 새로운 전문분야들이 생길 것이다. 5) 미래의 건강관리체계는 사회적인 변화와 이의 요구에 더 민감한 반응을 하게 될 것이다. 6) 건강관리체계의 강조점이 의료진료에서 건강관리로 바뀔 것이다. 7) 건강관리체계에서의 간호원의 역할은 의료적인 진단과 치료계획의 기능에서 크게 탈피하여 병원내외에서 보다 더 독특한 실무형태로 발전될 것이다. 이러한 변화와 더불어 미래 간호영역에서 보다 효과적인 간호를 수행하기 위해 미래 간호원들은 지금까지의 간호원보다 더 광범위하고 깊은 교육과 훈련을 받아야 한다. 보다 발전된 기술환경에서 전인적인 접근을 하기위해 신체과학이나 의학뿐 아니라 행동과학 $\cdot$ 경영과학 등에 이르기까지 다양한 훈련을 받아야 할 필요가 있다. 또한 행동양상면에서 전문직인 답게 보다 진취적이고 표현적이며 자동적이고 응용과학적인 역할을 수행하도록 훈련을 받아야 한다. 그리하여 간호원은 효과적인 의사결정자$\cdot$문제해결자$\cdot$능숙한 실무자일 뿐 아니라 소비자의 건강요구를 예리하게 관찰하고 이 요구에 효과적인 존재를 발전시켜 나가는 연구자가 되어야 한다. 2. 미래의 간호교육자는 어떤 역할을 수행해야 하는가? 간호교육은 전문직으로서의 실무를 제공하기 위한 기초석이다. 이는 간호교육자야말로 미래사회에서 국민의 건강요구를 충족시키기는 능력있는 간호원을 공급하는 일에 전무해야 함을 시사해준다. 그러면 이러한 일을 달성하기 위해 간호교육자는 무엇을 해야 하는가? 우선 간호교육자는 두가지 측면에서 이 일을 수정해야 된다고 본다. 그 하나는 간호교육기관에서의 측면이고 다른 하나는 간호교육자 개인적인 측면엣서이다. 우선 간호교육기관에서 간호교육자는 1) 미래사회에서 요구되는 간호원을 교육시키기 위한 프로그램을 제공해야 한다. 2) 효과적인 교과과정의 발전과 수정보완을 계속적으로 진행시켜야 한다. 3) 잘된 교과과정에 따라 적절한 훈련을 철저히 시켜야 한다. 4) 간호교육자 자신이 미래의 예측된 현상을 오늘의 교육과정에 포함시킬 수 있는 자신감과 창의력을 가지고 모델이 되어야 한다. 5) 연구 및 학생들의 학습에 영향을 미치는 중요한 의사결정에 학생들을 참여시키도록 해야한다. 간호교육자 개인적인 측면에서는 교육자 자신들이 능력있고 신빙성있으며 간호의 이론$\cdot$실무$\cdot$연구면에 걸친 권위와 자동성$\cdot$독창성, 그리고 인간을 진정으로 이해하려는 자질을 갖추도록 계속 노력해야 한다. 3. 미래의 간호원을 양성하는 능력있는 간호교육자를 준비시키기 위한 실질적이면서도 현실적인 전략은 무엇인가? 내일의 도전을 충족시킬 수 있는 능력있는 간호교육자를 준비시키기 위한 실질적이고 현실적인 전략을 논함에 있어 우리나라의 실정을 참조하겠다. 전문직 간호교육자를 준비하는데 세가지 방법을 통해 할 수 있다고 생각한다. 첫째는 간호원 훈련수준을 전문직 실무를 수행할 수 있는 단계로 면허를 높이는 것이고, 둘째는 훈련수준을 더 향상시키기 위하여 학사 및 석사간호교육과정을 발전시키고 확대하는 것이며, 셋째는 현존하는 간호교육 프로그램의 질을 높이는 것이다. 첫째와 둘째방법은 정부의 관할이 직접 개입되는 방법이기 때문에 여기서는 생략하고 현존하는 교과과정을 발전시키고 그 질을 향상시키는 것에 대해서만 언급하고자 한다. 미래의 여러가지 도전에 부응할 수 있는 교육자를 준비시키는 교육과정의 발전을 두가지 면에서 추진시킬 수 있다고 본다. 첫째는 국제간의 교류를 통하여 idea 및 경험을 나눔으로서 교육과정의 질을 높일 수 있다. 서로 다른 나라의 간호교육자들이 정기적으로 모여 생각과 경험을 교환하고 연구하므로서 보다 체계적이고 효과적인 발전체인(chain)이 형성되는 것이다. ICN같은 국제적인 조직에 의해 이러한 모임을 시도하는 것인 가치있는 기회라고 생각한다. 국가간 또는 국제적인 간호교육자 훈련을 위한 교육과정의 교환은 한 나라안에서 그 idea를 확산시키는데 효과적인 영향을 미칠 수 있다. 충분한 간호교육전문가를 갖춘 간호교육기관이 새로운 교육과정을 개발하여 그렇지 못한 기관과의 연차적인 conference를 가지므로 확산시킬 수도 있으며 이런 방법은 경제적인 면에서도 효과적일 뿐만 아니라 그 나라 그 문화상황에 적합한 교과과정 개발에도 효과적일 수 있다. 간호교육자를 준비시키는 둘째전략은 현존간호교육자들이 간호이론과 실무$\cdot$연구를 통합하고 발전시키는데 있어서 당면하는 여러가지 요인-전인적인 간호에 적절한 과목을 이수하지 못하고 임상실무경험의 부족등-을 보충하는 방법이다. 이런 실제적인 문제를 잠정적으로 해결하기 위하여 1) 몇몇 대학에서 방학중에 계속교육 프로그램을 개발하여 현직 간호교육자들에게 필요하고 적절한 과목을 이수하도록 한다. 따라서 임상실무교육도 이때 실시할 수 있다. 2) 대학원과정 간호교육프로그램의 입학자의 자격에 2$\~$3년의 실무경험을 포함시키도록 한다. 결론적으로 교수와 학생간의 진정한 동반자관계는 자격을 구비한 능력있는 교수의 실천적인 모델을 통하여서 가능하게 이루어 질수 있다고 믿는 바이다.

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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.

Effects of climate change on biodiversity and measures for them (생물다양성에 대한 기후변화의 영향과 그 대책)

  • An, Ji Hong;Lim, Chi Hong;Jung, Song Hie;Kim, A Reum;Lee, Chang Seok
    • Journal of Wetlands Research
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    • v.18 no.4
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    • pp.474-480
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    • 2016
  • In this study, formation background of biodiversity and its changes in the process of geologic history, and effects of climate change on biodiversity and human were discussed and the alternatives to reduce the effects of climate change were suggested. Biodiversity is 'the variety of life' and refers collectively to variation at all levels of biological organization. That is, biodiversity encompasses the genes, species and ecosystems and their interactions. It provides the basis for ecosystems and the services on which all people fundamentally depend. Nevertheless, today, biodiversity is increasingly threatened, usually as the result of human activity. Diverse organisms on earth, which are estimated as 10 to 30 million species, are the result of adaptation and evolution to various environments through long history of four billion years since the birth of life. Countlessly many organisms composing biodiversity have specific characteristics, respectively and are interrelated with each other through diverse relationship. Environment of the earth, on which we live, has also created for long years through extensive relationship and interaction of those organisms. We mankind also live through interrelationship with the other organisms as an organism. The man cannot lives without the other organisms around him. Even though so, human beings accelerate mean extinction rate about 1,000 times compared with that of the past for recent several years. We have to conserve biodiversity for plentiful life of our future generation and are responsible for sustainable use of biodiversity. Korea has achieved faster economic growth than any other countries in the world. On the other hand, Korea had hold originally rich biodiversity as it is not only a peninsula country stretched lengthily from north to south but also three sides are surrounded by sea. But they disappeared increasingly in the process of fast economic growth. Korean people have created specific Korean culture by coexistence with nature through a long history of agriculture, forestry, and fishery. But in recent years, the relationship between Korean and nature became far in the processes of introduction of western culture and development of science and technology and specific natural feature born from harmonious combination between nature and culture disappears more and more. Population of Korea is expected to be reduced as contrasted with world population growing continuously. At this time, we need to restore biodiversity damaged in the processes of rapid population growth and economic development in concert with recovery of natural ecosystem due to population decrease. There were grand extinction events of five times since the birth of life on the earth. Modern extinction is very rapid and human activity is major causal factor. In these respects, it is distinguished from the past one. Climate change is real. Biodiversity is very vulnerable to climate change. If organisms did not find a survival method such as 'adaptation through evolution', 'movement to the other place where they can exist', and so on in the changed environment, they would extinct. In this respect, if climate change is continued, biodiversity should be damaged greatly. Furthermore, climate change would also influence on human life and socio-economic environment through change of biodiversity. Therefore, we need to grasp the effects that climate change influences on biodiversity more actively and further to prepare the alternatives to reduce the damage. Change of phenology, change of distribution range including vegetation shift, disharmony of interaction among organisms, reduction of reproduction and growth rates due to odd food chain, degradation of coral reef, and so on are emerged as the effects of climate change on biodiversity. Expansion of infectious disease, reduction of food production, change of cultivation range of crops, change of fishing ground and time, and so on appear as the effects on human. To solve climate change problem, first of all, we need to mitigate climate change by reducing discharge of warming gases. But even though we now stop discharge of warming gases, climate change is expected to be continued for the time being. In this respect, preparing adaptive strategy of climate change can be more realistic. Continuous monitoring to observe the effects of climate change on biodiversity and establishment of monitoring system have to be preceded over all others. Insurance of diverse ecological spaces where biodiversity can establish, assisted migration, and establishment of horizontal network from south to north and vertical one from lowland to upland ecological networks could be recommended as the alternatives to aid adaptation of biodiversity to the changing climate.

REPORT OF EXPERIENCE WITH KIMURA'S DISEASE (기무라씨 질환, 5 예 보고)

  • Seel David J.;Park Yoon-Kyu;Lee Kwang-Min
    • Korean Journal of Head & Neck Oncology
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    • v.5 no.1
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    • pp.39-46
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    • 1989
  • Kimura's Disease is a chronic inflammatory and proliferative condition producing subcutaneous masses especially in the head and neck area. This report of our experience with 5 patients with this disease is the first in the Korean surgical literature. Kimura's Disease is thought to be part of the larger spectrum of the entity known as angiolymphoid hyperplasia with eosinophilia (ALHE). It is characterized pathologically by hyperplastic lymphoid follicles, eosinophilic infiltration, and vase 비 ar proliferation. It produces masses which are most common in the area of the parotid, submandibular gland and upper neck. These masses occupy the subcutaneous tissues but also extend into salivary tissue and into upper neck nodes. One of our patients had masses in the groin. The tumors are extremely vascular due to the presence of new proliferative vessels and sinusoids. The average age of our 5 patients was 35, but all but one case were younger than 38 years of age. The male: female ratio was 3 : 2, and the average duration of symptoms was 5,2years. All patients had peripheral blood eosinophilia. All had multiple masses, sometimes symmetrical. The management was surgery alone in one case, surgery and steroids in one case, surgery and radiotherapy in two cases, and all three modalities in one case. The relationship of this entity to ALHE and our experience in the management of this disease are presented. A clinicopathological discrepancy alerted us to the existence of Kimura's Disease. A nineteen-year old male presented with subcutaneous masses over both mastoid areas present for 3 years (Case III). When biopsy on each side was reported as 'eosinophilic granuloma' we submitted the slides to an internationally expert pathologist. Symmetrically occurring tumors in the peri-parotid subcutaneous areas did not fit any category of neoplasm or granuloma known to us. The diagnosis, made by Dr. Gist Fan at the Ochsner Clinic, was Kimura's Disease. We found two additional cases in a review of soft tissue eosinophilic granuloma previously reported at Presbyterian Medical Center, and since then have diagnosed two new cases. These five cases constitute the basis for this, the largest series to be reported in Korea. These vascular, tumor-like lesions of the skin, subcutaneous areas and subjacent structures of the head and neck have been a variety of names, such as angiolymphoid hyperplasia with eosinophilia, eosinophilic hyperplastic lymphogranuloma, angioblastic lymphoid hyperplasia with eosinophilia, histioid hemangioma, and epithelioid hemangioma. The history of this disease spectrum dates back to 1937 when Kimm and Szeto (1) reported 7 cases of 'eosinophilic hyperplastic lymphogranuloma' in the Proceedings of the Chinese Medical Journal. In 1948 Kimura and his associates(2) reported additional cases in Japan under the title 'On the unusual granulation combined with hyperplastic changes of lymphatic tissue.' From then until 1966 several hundred cases were reported in China and Japan. The first report from the West was by Wells and Whimster(3) in the British Journal of Dermatology, in 1969. These authors coined the term, angiolymphoid hyperplasia with eosinophilia (ALHE). Since that time a debate has ensued as to whether Kimura's Disease and ALHE are distinct entities, or whether Kimura's is part of the larger spectrum of ALHE, perhaps a later or advanced phase. From the clinical perspective, surgeons should be aware of the diagnosis of Kimura's Disease not only as part of the differential diagnosis of head and neck tumors but also because these lesions are indolent, and generally require conservative surgical removal as part of the management program. CASE I. A 37-year-old female company employee presented in August 1982 with submental swelling of 12 years' duration and with inguinal swelling of 7 years' duration. The submental mass measured 5x5cm. and the inguinal mass was 8x4cm. in size. Peripheral eosinophilia varying from 14% to 40% was found. On August 20, 1982, the submental mass was removed and a superficial groin dissection was done. In May 1983 an intraoral lesion of the palate was removed. The patient is free of disease. CASE II. A 23-year-old unemployed man visited this hospital for the first time in July, 1984, with swelling of the right cheek present for 6 years. The mass was soft and ill-defined but measured 10x20cm. and extended from the submandibular upper neck to the zygomatic arch, and from the mastoid to the cheek, over the parotid gland. Eosinophilia varying from 27% to 29% was noted in the peripheral blood. On March 21, 1986, the lesion was resected. The procedure comprised an extended superficial parotidectomy from the temporalis fascia to the upper neck. Post-operatively radiotherapy 3000 rad tissue dose was administered using the 6 MeV linear accelerator. The patient remains free of disease. CASE III. A 19-year-old student came to the clinic with masses over both mastoid areas, present 3 years. On the right there were two adjacent lesions, one over the mastoid, the other in the upper jugular level of the neck. On the left it was a single mass over the mastoid. Eosinophilia varied from 13 to 32% in the peripheral blood, and 11.6% in the bone marrow. Incisional biopsy revealed 'eosinophilic granuloma' and a trial of predisolone was employed. The mass increased in size so a small dose of radiation (600 rads) was used, with substantial regression,. The lesion on the left was excised and follwed by 1000 rads radiotherapy. Finally recurrent tumor on the right side was removed on November 5, 1985. The patient remains free of disease. CASE N. A 29-year-old local merchant had had swelling of both upper necks since childhood. At the time of his first visit on March 17, 1986, the right submandibular mass measured 5x3.5cm. and the ,right upper neck and parotid tail mass measured 2.5cm. On the left there were masses in the upper neck, the largest of which measured 2.5cm, and of the parotid tail, 2.0cm. in size.(See Fig. 1) Peripheral eosinophilia of 39% was recorded. Left side partial parotidectomy and resection of the upper neck and subdigstric mases was done on May 2, 1986. The mass involving the right parotid tail and upper neck nodes was removed on Angust 7,1986. Postoperatively the patient was placed on prednisolone 30 mg. per day. No definite masses are palpable. CASE V. A 66-year-old housewife informed us, at the time of her first visit in May, 1986, that she had had multiple neck masses since 10 years ago. On the right side there was a 2.5cm. subcutaneous mass of the upper neck, over the upper jugular chain. On the left there was a 9x4.5cm. mass involving the entire parotid, the post-auricular area and the upper neck. A third mass presented in the submental area and measured 3.5cm. (See Fig. 2) Eosinophilia of 51% was noted in the peripheral blood. partial excision of the left upper neck lesion and complete excision of the submental mass were performed on june 6, 1986. post-operatively she was placed on 20 mg. of prednisolone daily, but when the mass re-grew after two months she was referred to Radiation Therapy for a 2500 rad course of treatment. A barely palpable thickening remains.

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The Present Status and a Proposal of the Prospective Measures for Parasitic Diseases Control in Korea (우리나라 기생충병관리의 현황(現況)과 효율적방안에 관(關)한 연구(硏究))

  • Loh, In-Kyu
    • Journal of Preventive Medicine and Public Health
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    • v.3 no.1
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    • pp.1-16
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    • 1970
  • The present status of control measures for public health important helminthic infections in Korea was surveyed in 1969 and the following results were obtained. The activities of parasitic examination and Ascaris treatment for the positives which were done during 1966 to 1969 were brought in poor result and could not decrease the infection rate. It is needed to improve or strengthen the activities. The mass treatment activities for paragonimiasis and clonorchiasis in the areas which were designated by the Ministry of Health were carried out during 1965 to 1968 with no good results in decrease of estimated number of the patients. There were too many pharmaceutical companies where many kinds of anthelmintics were produced. It may be better to reduce the number of anthelmintics produced and control the quality. The human feces, the most important source of helminthic infections, was generally not treated in sanitary ways because of the poor sewerage system and no sewage treatment plant in urban areas and insanitary latrines in rural areas. The field soils of 170 specimens were collected from 34 areas out of 55 urban and tourist areas where night soil has been prohibited by a regulation to be used as a fertilizer, and examined for parasites contamination with the result of Ascaris egg detection in 44%. Some kinds of vegetables of 64 specimens each from the supply agents of parasite free vegetables and general markets were collected and examined for parasites contamination with the results of Ascaris egg detection in 25% and 36% respectively. The parasite control activities and the ability of parasitological examination techniques in the health centers of the country were not satisfactory. The budget of the Ministry of Health for the parasite control was very poor. The actual expenditure needed for cellophane thick smear technique was 8 Won per a specimen. As a principle the control of helminthic infections might be led toward breaking the chain of events in the life cycle of the prasites and eliminating environmental and host factors concerned with the infections, and the following methods nay be pointed out. 1) Mass treatment might be done to eliminate human reservoirs of an infection. 2) Animal reservoirs which are related with human infections night be eliminated. 3) The excretes of reservoirs, particularly human feces, should be treated in sanitary ways by the means of sanitary sewerage system and sewage treatment plant in urban areas and sanitary latrines such as waterborne latrine, aqua privy and pit latrine in rural areas. The increase of national economical development and prohibition of the habit of using night soils as a fertilizer might be very important factors to achieve the purpose. 4) The control of vehicles and intermediate hosts might be done by the means of prohibition of soil contamination with parasites, food sanitation, insect control and snail control. 5) The improvement of insanitary attitudes and bad habits which are related with parasitic infections night be done by the means of prohibition of habit of using night soils as a fertilizer, and improving eating habits and personal hygiene. 6) Chemoprophylactic measure and vaccination may be effective to prevent the infections or the development of a parasite to adult in the bodies when the bodies were invaded by parasites. Further studies and development of this kind of measures are needed.

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Correlation of p53 Protein Overexpression, Gene Mutation with Prognosis in Resected Non-Small Cell Lung Cancer(NSCLC) Patients (비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향)

  • Lee, Y.H.;Shin, D.H.;Kim, J.H.;Lim, H.Y.;Chung, K.Y.;Yang, W.I.;Kim, S.K.;Chang, J.;Roh, J.K.;Kim, S.K.;Lee, W.Y.;Kim, B.S.;Kim, B.S.
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.339-353
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    • 1994
  • Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

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