232 research outputs found

    ๋ณต์ง€, ์•ˆ์ „๊ตญํ†  ์‹คํ˜„๊ณผ ๊ณต๊ฐ„๋น…๋ฐ์ดํ„ฐ ํ™œ์šฉ

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    ๋…ธํŠธ : [ํŠน์ง‘ | ๊ณต๊ฐ„๋น…๋ฐ์ดํ„ฐ์™€ ์ƒˆ๋กœ์šด ๊ตญํ† ๊ฐ€์น˜ ์ฐฝ์ถœ 2

    Altered Intestinal Permeability and Drug Repositioning in a Post-operative Ileus Guinea Pig Model

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    Background/aims: The aim of this study is to identify the alteration in intestinal permeability with regard to the development of post-operative ileus (POI). Moreover, we investigated drug repositioning in the treatment of POI. Methods: An experimental POI model was developed using guinea pigs. To measure intestinal permeability, harvested intestinal membranes of the ileum and proximal colon was used in an Ussing chamber. To identify the mechanisms associated with altered permeability, we measured leukocyte count and expression of calprotectin, claudin-1, claudin-2, and mast cell tryptase. We compared control, POI, and drug groups (mosapride [0.3 mg/kg and 1 mg/kg, orally], glutamine [500 mg/kg, orally], or ketotifen [1 mg/kg, orally] with regard to these parameters. Results: Increased permeability after surgery significantly decreased after administration of mosapride, glutamine, or ketotifen. Leukocyte counts increased in the POI group and decreased significantly after administration of mosapride (0.3 mg/kg) in the ileum, and mosapride (0.3 mg/kg and 1 mg/kg), glutamine, or ketotifen in the proximal colon. Increased expression of calprotectin after surgery decreased after administration of mosapride (0.3 mg/kg), glutamine, or ketotifen in the ileum and proximal colon, and mosapride (1 mg/kg) in the ileum. The expression of claudin-1 decreased significantly and that of claudin-2 increased after operation. After administration of glutamine, the expression of both proteins was restored. Finally, mast cell tryptase levels increased in the POI group and decreased significantly after administration of ketotifen. Conclusions: The alteration in intestinal permeability is one of the factors involved in the pathogenesis of POI. We repositioned 3 drugs (mosapride, glutamine, and ketotifen) as novel therapeutic agents for POI.ope

    On the meaning and distribution of the focus-sensitive particle acik

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    ์•„์ง์— ๋Œ€ํ•œ ๋…ผ์˜๋Š” ์ด๋ฏธ๋‚˜ ๋ฒŒ์จ์™€ ํ•จ๊ป˜ ์ƒ๋ถ€์‚ฌ(aspectual adverb)๋กœ์„œ์˜ ์˜๋ฏธ์— ์ง‘์ค‘๋˜์–ด ์™”๋‹ค(๊น€์ง„์ˆ˜ 1985, ๊น€์„ ํฌ 1987, ์ž„์„œํ˜„, ์ด์ •๋ฏผ 1999 ๋“ฑ). ์•„์ง์€ ํ‰๊ฐ€์‹œ(reference time)์— ์ง€์†๋˜๊ณ  ์žˆ๋Š” ์–ด๋–ค ์ƒํƒœ๊ฐ€ ํ‰๊ฐ€ ์‹œ ์ดํ›„์— ๋ณ€ํ™”ํ•  ๊ฒƒ์„ ํ•จ์ถ•ํ•˜๋Š” ๋ถ€์‚ฌ๋กœ ๊ธฐ์ˆ ๋˜๋ฉฐ, ์ด๋Ÿฌํ•œ ์˜๋ฏธ๋Š” ์ง€์†(continuity)์˜ ์ƒ์  ํŠน์„ฑ์„ ๋ณด์ด๋Š” ๋งฅ๋ฝ์— ๋‚˜ํƒ€๋‚˜๋Š” ์•„์ง์˜ ๋ถ„ํฌ ์ œ์•ฝ๊ณผ ์—ฐ๊ฒฐ๋˜๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค(์ด์ง€์˜ 2010). ๋ฐ˜๋ฉด Y Jun (1998)๊ณผ EH Lee (2008)์€ ์ƒ๋ถ€์‚ฌ๊ฐ€ ๊ฐ–๋Š” ์ดˆ์ ์‚ฌ์  ํŠน์„ฑ์— ๊ด€์‹ฌ์„ ๋‘๊ณ  ์•„์ง์€ ์ƒ๋ถ€์‚ฌ๋กœ, ๋ณด์กฐ์‚ฌ์™€ ๊ฒฐํ•ฉํ•œ ์•„์ง๋„๋Š” ์ดˆ์ ๋ถ€์‚ฌ(focus adverb) ๋กœ ๊ตฌ๋ถ„ํ•˜์˜€๋‹ค. ์ดˆ์ ์‚ฌ๋กœ์„œ์˜ ์ƒ๋ถ€์‚ฌ๋Š” ๋ฌธ์žฅ์ด ๊ธฐ์ˆ ํ•˜๋Š” ์ƒํƒœ์— ๋Œ€ํ•œ ๋‹จ์–ธ๊ณผ ๋”๋ถˆ์–ด, ๋ฐ˜๋Œ€์˜ ๊ทน์„ฑ์„ ๊ฐ€์ง„ ์„ ํƒ์ง€(alternative)์— ๋Œ€ํ•œ ๋ถ€์ •์„ ํ†ตํ•ด ๋‘ ์ƒํƒœ์˜ ๋Œ€์กฐ๋ฅผ ํ‘œํ˜„ํ•œ๋‹ค. ์ตœ๊ทผ Y Lee (2011)์€ ์•„์ง์˜ ์šฉ๋ฒ•์„ ์ƒ์ ์ธ ๊ฒƒ๊ณผ ์ฒ™๋„์ ์ธ ๊ฒƒ ๋‘ ๊ฐ€์ง€๋กœ ๊ตฌ๋ถ„ํ•˜๊ณ , ๋‘ ์šฉ๋ฒ•์ด ๊ฐ๊ธฐ ๋‹ค๋ฅธ ์ดˆ์ ์‚ฌ(focus particle)์— ์—ฐ๊ฒฐ๋˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์•˜๋‹ค.This paper proposes that the aspectual adverb acik in Korean, often translated as still or yet, is a focus-sensitive particle that exploits alternatives on a temporal scale. Acik is a kind of exclusive particle that selects the lowest bound on a temporal scale and denies the upper values, thus yielding a negative entailment even in positive sentences. It is shown that the distributional constraints of acik follow from the proposed semantics and the properties of a temporal scale. Acik can occur only in contexts where some upper or later elements can be assumed. In addition to the well-known imperfective constructions due to progressives, resultatives, and negation and negative predicates, this paper newly identifies a set of constructions that allow acik such as degree adverb tel less with accomplishment predicates, modal constructions of possibility and necessity, before-clauses, and imperatives and exhortatives with negative force. All these constructions make a temporal scale possible, and the adverb conveys a contrast between the current phase and the possible next phase that has not been realized yet.์ด ๋…ผ๋ฌธ์€ 2013ํ•™๋…„๋„ ์„œ์šธ์—ฌ์ž๋Œ€ํ•™๊ต ์—ฐ๊ตฌ๋…„ ์—ฐ๊ตฌ๋น„์˜ ์ง€์›์„ ๋ฐ›์•˜์Œ

    ์˜ฅ์„ธํ‹ฑ ๊ตฌ์กฐ๊ฐœ๋ฐœ์„ ํ†ตํ•œ ์†Œํ”„ํŠธ ์žฌ๋ฃŒ์˜ ๋ณ€ํ˜•ํŠน์„ฑ ์„ค๊ณ„ ๋ฐ ์œ ์—ฐ์†Œ์ž ์ ์šฉ์— ๋Œ€ํ•œ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› ๊ณต๊ณผ๋Œ€ํ•™ ์žฌ๋ฃŒ๊ณตํ•™๋ถ€, 2017. 8. ์ฃผ์˜์ฐฝ.As the development of flexible devices has progressed for user's convenience, researches on the rational design of architectures and structures which could provide mechanical functionality to flexible devices, have been actively carried out as well as material development perspective. The control of mechanical properties through structural innovation has the advantage that it provides unprecedented properties beyond the existing material limits and is easy to design predictably. Based on this feature, there is a growing interest in reconfigurable materials that could operate in response to external physical stimuli. Auxetics, which are one of the mechanically reconfigurable materials, is a structure which are able to perform negative Poisson's ratio behavior. Based on the characteristics, auxetics have an excellent expandability and possible to maintain an excellent conformability even on a non-zero Gaussian surface. Therefore, auxetics are an attracting attention as a structural material for a next generation flexible device. In this thesis, the mechanical and electrical performance of flexible devices were improved through proper geometric design of two dimensional auxetic structure, and suggested auxetics as a new paradigm of structural materials for flexible devices. At first, a platform for flexible devices was proposed, which was capable of large displacement in all directions by using a rotational unit auxetic including a self-similar hierarchical structure. Through the finite element analysis, it was proved that even if the hierarchical auxetic was subjected to complicated deformation, not only the tension but also crumpling, the deformation could be concentrated only in the hinges connecting the individual unit. Based on the deformation characteristics, an omnidirectionally and extremely deformable battery was developed. When the hinge was composed of an elastomer having excellent mechanical reliability, it was possible to deform the hinge in an unexpected three dimensional manner beyond the viewpoint of the conventional two dimensional auxetic view. As a result, the degree of freedom of hinge deformation could be increased to infinity. Also, as the level of the hierarchical structure increased, the strain concentrated on the hinge is relaxed even at the same level of strain, thereby improving the mechanical stability and improving the stretchability and be crumpled easily. In addition, it was possible to design the same hierarchical auxetic in a thin plastic substrate through the cutting process. In this case, the sharp cut pattern could cause tearing, which could result in severe mechanical failure. To improve the mechanical reliability at the hinge, a design to prevent the crack propagation was proposed, thereby confirmed the potential ability of applying the hierarchical auxetic to thin sheets. Secondly, a hybrid auxetic composite had been developed which could be predictably design the modulus of elasticity and Poisson's ratio, by embedding two dimensional re-entrant auxetic as a composite scaffold into soft material. This composite could have an anisotropic deformation behavior due to the influence of re-entrant structure, which had a negative Poisson's ratio behavior in in-plane and a positive Poisson's ratio in the normal direction. Especially, the thickness of matrix in the composite could be decreased even more compared to the conventional isotropic materials due to the volume conservation. Using the anisotropic mechanical property of composite, a stretchable capacitive strain sensor having improved sensing property was developed which could stretch up to 50 %. The Gauge factor, which is a ratio of change in capacitance to the stretch, of the conventional capacitive strain sensor was limited to 1 due to the geometric factor. Applying the auxetic composite as a dielectric, sharper capacitance change was achieved even under the same degree of stretch compared to the conventional sensor. In addition to the improvement, the composites could represent a good conformability to such as elbows and knees, thus our composites could suggest a new direction in geometry design for wearable sensors. This thesis suggested auxetics as a new paradigm as a structural material for flexible devices by improving the mechanical and electrical performance of various flexible devices that are currently being developed, by properly customizing the architectural design.Chapter 1. Introduction 1.1. Emergence of soft electronics ......... 1 1.2. Necessity of geometric design for soft electronics .. 4 1.3. Auxetic: A new geometric concept for soft electronics ............ 6 1.4. Thesis objectives ....................................................... 12 1.5. Organization of the thesis ....................................................... 13 Chapter 2. Theoretical Background 2.1. Neo-Hookean solid ..................................... 14 2.2. Theoretical limit in Poissons ratio of istropic material ......... 16 2.3. Auxetic ......... 18 2.3.1. Classification of auxetic ................................................ 18 2.3.2. Mechanical model for re-entrant auxetic ................. 21 2.4. Mechanism of strain sensor ................................................ 23 Chapter 3. Hierarchical Auxetic for Extremely deformable Device Platform 3.1. Introduction ................................................................. 25 3.2. 3-dimensional deformation of soft hierarchical auxetic ............. 29 3.3. Experimental procedure ........................... 37 3.4. FEM for 3-D deformation of hierarchical auxetic .... 41 3.4.1. Tensile deformation model ........................................... 43 3.4.2. Crumple deformation model ........................................... 47 3.4.3. Motif array dependence ........................................... 53 3.5. Experimental realization ............................................... 56 3.4.1. Mechanical reliability confirmation of hinge ............ 56 3.4.2. Omni-directionally deformable batteries ............ 59 3.4.3. Hierarchical auxetic design for thin film application ......... 61 3.6. Summary ................................................................... 65 Chapter 4. Tunable Elastic Property of Soft Materials by Auxetic Composites and Strain Sensing Application 4.1. Introduction .............................................................................. 66 4.2. Experimental procedure ...................................... 71 4.2.1. Fabrication of auxetic composite ...................................... 71 4.2.2. Fabrication and measurement of strain sensor ...................... 75 4.3. Tensile behavior of auxetic composite .... 77 4.4. Auxetic composite design through FEM .... 81 4.4.1 Determination of elastic property of composite element .... 81 4.4.2. Stretch direction dependence of re-entrant auxetic .... 83 4.4.3. Boundary condition for stretch of auxetic composite .... 86 4.4.4. Geometric dependence ............................................ 92 4.4.5. Material dependence ............................................ 101 4.4.6. Thickness dependence of auxetic composite .... 103 4.5. Hybrid auxetic composite for capacitive strain sensor .... 109 4.5.1. Performance of auxetic strain sensor ................................ 110 4.5.2. Capacitance calculation by FEM ................................ 112 4.5.3. Analytic model for predicting gauge factor ........................ 115 4.6. Summary ...................................................................................... 121 Chapter 5. Conclusion 5.1. Summary of results .................................................................... 122 5.2. Future work and suggested research ...................................... 124Docto

    ๋‘๋ณด ์—ฐ์ž‘์‹œ์˜ ์žฅ๋ฒ• ์—ฐ๊ตฌ

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    ์—ฐ์ž‘์‹œ๋Š” ๋ช‡ ์ˆ˜์˜ ๊ฐœ๋ณ„์‹œ๊ฐ€ ๋™์ผํ•œ ่ฉฉ้กŒ ์•„๋ž˜ ์กฐํ•ฉ๋œ ์‹œ์ด๋‹ค. ์—ฐ์ž‘์‹œ๋ฅผ ์ด๋ฃจ๋Š” ๊ฐœ๋ณ„์‹œ๊ฐ€ ๊ฐ๊ธฐ ๋…๋ฆฝ์ ์œผ๋กœ ์˜จ์ „ํ•œ ์‹œ์ƒ์„ ํ‘œํ˜„ํ•˜๋ฉด์„œ ๋™์‹œ์— ๊ฐœ๋ณ„์‹œ ์ƒํ˜ธ๊ฐ„์— ๋‚ด์šฉ์ƒ์˜ ์—ฐ๊ณ„์„ฑ์ด ์žˆ์–ด์•ผ ์ œ๋Œ€๋กœ ๋œ ์—ฐ์ž‘์‹œ๋ผ ํ•  ์ˆ˜ ์žˆ๋‹ค. ๋‘๋ณด๋Š” ๋‹ค์ˆ˜์˜ ์—ฐ์ž‘์‹œ๋ฅผ ์ง€์—ˆ๋Š”๋ฐ, ๋Œ€๋‹ค์ˆ˜์˜ ๊ฒฝ์šฐ ๊ณ„ํš๋œ ๊ตฌ์ƒ์— ๋”ฐ๋ผ ๊ฐ ๊ฐœ๋ณ„์‹œ์˜ ์‹œ์ƒ์ด ์•ˆ๋ฐฐ๋˜๊ณ  ์—ฐ๊ณ„๋˜์–ด ํ•˜๋‚˜์˜ ์™„์ •ํ•œ ํ†ตํ•ฉ์„ ๋ณด์ธ๋‹ค. ์ฆ‰ ์—ฐ์ž‘์‹œ ์ „์ฒด๋ฅผ ๋ฌถ์–ด์„œ ํ•œ ํŽธ์˜ ์‹œ์ฒ˜๋Ÿผ ๋ณด์ด๋„๋ก ์น˜๋ฐ€ํ•œ ์žฅ๋ฒ•์„ ๊ตฌ์‚ฌํ•œ ๊ฒƒ์ธ๋ฐ, ์ด๋Ÿฐ ์—ฐ์ž‘์‹œ๋Š” ๋‘๋ณด ์ด์ „์˜ ์‹œ์ธ์—๊ฒŒ์„œ๋Š” ๊ฑฐ์˜ ์ฐพ์„ ์ˆ˜ ์—†์—ˆ๋˜ ๊ฒƒ์ด๋‹ค. ๋‘๋ณด๋Š” ์‹œ์˜ ๋‚ด์šฉ์ด๊ฑด ํ˜•์‹์ด๊ฑด ๊ฐ„์— ์งˆ์„œ ์žˆ๊ณ  ํ†ตํ•ฉ๋œ ๊ตฌ์กฐ๋ฅผ ์ด๋ฃจ๊ณ ์ž ํ•˜์˜€๋Š”๋ฐ, ์—ฐ์ž‘์‹œ ์ „์ฒด๋ฅผ ๋ฌถ์–ด ํ•œ ํŽธ์˜ ์‹œ์ฒ˜๋Ÿผ ์ง“๊ณ ์ž ํ•œ ๋ฐ์—๋„ ๊ทธ์˜ ์ด๋Ÿฐ ไฝœ่ฉฉ ์›์น™์ด ์ ์šฉ๋˜์—ˆ์„ ๊ฒƒ์ด๋‹ค. ๋‘๋ณด ์—ฐ์ž‘์‹œ์˜ ์žฅ๋ฒ•์ด ์กฐ์ง์ ์ด๋ผ๋Š” ์‚ฌ์‹ค์— ๋Œ€ํ•˜์—ฌ ์ด์ „์˜ ๋‘์‹œ ์ฃผ์„๊ฐ€๋“ค์ด ์ด๋ฏธ ๊ทธ ๊ตฌ์ฒด์ ์ธ ์˜ˆ๋ฅผ ๋“ค์–ด ์ง€์ ํ•˜์˜€๋‹ค. ใ€ˆๆ•ฃๆ„ไบŒ้ฆ–(์‹œ๋ฆ„์„ ํ’€๋‹ค)ใ€‰์˜ ์žฅ๋ฒ•์— ๋Œ€ํ•œ ็Ž‹ๅ—ฃๅฅญ์˜ ๋‹ค์Œ ํ‰์„ ๋ณด์ž. ๆœ็”ซๆ›พๅ‰ตไฝœๅ‡บ่ซธๅคš้€ฃไฝœ่ฉฉ, ็ต•ๅคงๅคšๆ•ธๆƒ…ๆณไน‹ไธ‹่ฉฉไบบๅ‰‡ๆœƒๆ นๆ“š่‡ชๅทฑ่จˆๅŠƒๅฅฝ็š„ๆง‹ๆƒณๅฎ‰ๆŽ’ๅ€‹ๅˆฅ่ฉฉ็š„ๆง‹ๆ€, ๅพž่€Œๅฐ‡ๅ…ถ้€ฃๆŽฅ่ตทไพ†, ๅฝขๆˆไธ€ๅ€‹ๅฎŒๆ•ด็š„็ตฑๅˆ้ซ”ใ€‚ ๅณๆ˜ฏ่ชช็‚บไบ†ๅฐ‡ๆ•ดๅ€‹้€ฃไฝœ่ฉฉๆ†็ถ็‚บไธ€ๅ€‹ๆ•ด้ซ”ๅพž่€Œ็ทจ็น”ๆˆไธ€้ฆ–่ฉฉ, ๆง‹ๆƒณๅ‡บ็ธๅฏ†็š„็ซ ๆณ•ใ€‚ ๆˆ‘ๅ€‘ๅœจๆ—ฉๅ‰็š„่ฉฉไบบ้‚ฃ้‡Œๆ นๆœฌ็„กๆณ•่ฆ“ๅพ—้€™็จฎ้€ฃไฝœ่ฉฉ็š„็—•่ทกใ€‚ ๅฐไบŽๆœ่ฉฉ้€ฃไฝœ่ฉฉ็ซ ๆณ•ไน‹ๅŽŸ็†, ๅฏไปฅๆฆ‚ๆ‹ฌ็‚บๅฆ‚ไธ‹ๅ…ฉ้ปž: ไธ€ๅ€‹ๆ˜ฏๆ‡‰่ฉฒ็ขบไฟๅพ—ไปฅๆง‹ๆˆ้€ฃไฝœ่ฉฉ็š„ๅ€‹ๅˆฅ่ฉฉไน‹้–“็š„้€ฃๆŽฅๆ€ง; ๅฆไธ€ๅ€‹ๅ‰‡ๆ˜ฏๆ‡‰่ฉฒๅฎ‰ๆŽ’ๆ•ด้ซ”่ฉฉ็š„ๆง‹ๆƒณ, ๅพž่€Œๅˆถๅฎšๅ‡บ้กžไผผไธ€้ฆ–่ฉฉ็š„ๆก†ๆžถใ€‚ ๆˆ‘ๅ€‘ๅœจใ€Šๆ•ฃๆ„ไบŒ้ฆ–ใ€‹็ญ‰่ฉฉ่ฃ่ƒฝ็œ‹ๅˆฐๅ‰่€…ๅ…ท้ซ”็š„้ข่ฒŒ; ่€ŒๅŽ่€…ๅ‰‡ไธป่ฆ้ซ”็พไบŽใ€Š็พŒๆ‘ไธ‰้ฆ–ใ€‹่ฃใ€‚ ๆœ็”ซ็‚บ็ขบไฟ้€ฃไฝœ่ฉฉ็š„้€ฃๆŽฅๆ€ง, ไธๅƒ…ๅฎ‰ๆŽ’่ฉฉ็š„ๅ…งๅฎน, ่€Œไธ”้‚„ๆดป็”จ่ฉฉ็š„ๆ ผๅพ‹, ๅฐคๅ…ถๆ˜ฏๅˆฉ็”จๅฐไป—ๅฐ‹ๆฑ‚่ฉฉไน‹ๆง‹ๆƒณ็š„้€ฃๆŽฅ

    Identification and characterization of preexisting resistant subclone in lung cancer with EGFR mutation sensitive to EGFR tyrosine kinase inhibitor

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    ์˜๊ณผ๋Œ€ํ•™/๋ฐ•์‚ฌEGFR tyrosine kinase inhibitor (EGFR-TKI) is the first molecularly targeted drug to change the paradigm in the management of lung cancer. These drugs are specifically effective in lung cancers with activating EGFR mutations. However, most cancer that initially responds to EGFR-TKI eventually acquires drug resistance. Several mechanisms are responsible for acquired resistance to EGFR-TKI, and the most common is the emergence of the T790M mutation in EGFR. This study aimed to evaluate whether the tumor cells carrying the T790M mutation exists before drug exposure and expands under the selective drug pressure. We collected pretreatment tumor tissues from 124 advanced non-small cell lung cancer patients with activating EGFR mutations that were detected by direct sequencing. Genotyping for T790M by matrix-assisted laser desorption/ionization-time of flight/mass spectrometry identified 31 (25.0%) tumors with pretreatment T790M. Furthermore, 68 cases which additionally underwent droplet digital PCR showed 27 (39.7%) tumors had pretreatment T790M mutation. We also observed clonal expansion of preexisting T790M clones during EGFR-TKI treatment both in in vivo model and in the paired tissue samples. In co-culture study mixing drug-sensitive cell and luciferase-tagging drug-resistant cell, we showed this growth advantage of resistant cell in regressing tumors was caused by dying sensitive cells. The T790M mutation frequency at which the risk of progression to EGFR-TKI begins to increase was estimated to be 3.2%. The patients with T790M-positive tumor had shorter time to progression (TTP) after EGFR-TKI (median 6.3 months vs. 11.5 months; P < 0.001) and overall survival (OS) (median 16.1 months vs. 26.5 months; P = 0.065) than those with T790M-negative tumor. Among the T790M-positive patients, the patients with high T790M frequency (n= 9) had shorter TTP (median 2.4 months vs. 6.7 months; P = 0.009) and OS (median 9.1 months vs. 18.7 months; P = 0.018) than those with low T790M frequency (n= 22). In conclusions, EGFR T790M mutation preexisted substantially in EGFR-mutant lung cancer. The T790M clones may expand during EGFR-TKI treatment by dying sensitive cell and finally be responsible for the patientsโ€™ resistance and progression. Thus, the patients with high T790M mutation frequency had worse clinical outcomes to EGFR-TKI.ope

    The study on Cancer invasion and Epithelial-Mesenchymal Transition by STAT3 and CXCR4 in Glioblastoma primary cells

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜๊ณผํ•™๊ณผ ์˜๊ณผํ•™ ์ „๊ณต, 2013. 2. ์˜ˆ์ƒ๊ทœ.๊ต๋ชจ์„ธํฌ์ข… (glioblaastoma) ์€ ๋งค์šฐ ์นจ์Šต์ ์ด๋ฉฐ ๋น ๋ฅด๊ฒŒ ์ฆ์‹ํ•˜๋Š” ์•…์„ฑ์˜ ๋‡Œ์ข…์–‘์ด๋‹ค. ๊ต๋ชจ์„ธํฌ์ข…์˜ ์กฐ๊ธฐ ์ง„๋‹จ๊ณผ ์น˜๋ฃŒ์— ์žˆ์–ด ๊ด„๋ชฉํ• ๋งŒํ•œ ๋ฐœ์ „์„ ์ด๋ฃจ์—ˆ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ , ์ข…์–‘์˜ ๊ธ‰๊ฒฉํ•œ ์ฆ์‹๊ณผ ์žฌ๋ฐœ ๋“ฑ์˜ ์ด์œ ๋กœ ๋งŽ์€ ํ™˜์ž๋“ค์€ ์ง„๋‹จ ์ดํ›„ 1๋…„ ์ด๋‚ด์— ์‚ฌ๋งํ•˜๊ณ  ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ด๋Ÿฌํ•œ ์š”์ธ๋“ค์— ๊ด€ํ•œ ์ •ํ™•ํ•œ ์›์ธ๊ณผ ๋ฉ”์ปค๋‹ˆ์ฆ˜์ด ๋ฐํ˜€์ง€์ง€ ์•Š์€ ๊ฐ€์šด๋ฐ, ๊ต๋ชจ์„ธํฌ์ข…์—์„œ์˜ STAT3 (Signal Transducer and activator of transcription 3) ์™€ CXCR4 (C-X-C chemokine receptor type 4) ๋ฐœํ˜„์— ๋Œ€ํ•œ ๊ด€์‹ฌ์ด ์ฆ๋Œ€๋˜๊ณ  ์žˆ๋‹ค. STAT3๋Š” ๋Œ€๋ถ€๋ถ„์˜ ์ข…์–‘์— ํ™œ์„ฑํ™”๋˜์–ด ์žˆ๋‹ค๊ณ  ์•Œ๋ ค์ง„ ์ „์‚ฌ์ธ์ž๋กœ์„œ ๊ต๋ชจ์„ธํฌ์ข… ์ค„๊ธฐ์„ธํฌ์˜ ์ฆ์‹๊ณผ ์—ฐ๊ด€์„ฑ์ด ๋ฐํ˜€์ง„ ๋ฐ” ์žˆ์œผ๋ฉฐ, CXCR4๋Š” chemokine receptor๋กœ ์‹ ๊ฒฝ ๊ต์ข…์„ธํฌ์˜ ์นจ์œค์„ฑ์„ ๋งค๊ฐœํ•œ๋‹ค๊ณ  ๋ณด๊ณ ๋œ ๋ฐ” ์žˆ๋‹ค. ์ด๋Ÿฌํ•œ ๋‹จ๋ฐฑ์งˆ๋“ค์˜ ๋ฐœํ˜„์€ ์„ธํฌ์˜ ์ด๋™ํ˜„์ƒ์ธ ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰ (Epithelial-Mesenchymal Transition) ๊ณผ๋„ ๋ฐ€์ ‘ํ•œ ๊ด€๋ จ์„ฑ์ด ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ์•…์„ฑ ๊ต๋ชจ์„ธํฌ์ข…์—์„œ STAT3์™€ CXCR4๋Š” ๋ชจ๋‘ EMT ํ˜„์ƒ์„ ํ†ตํ•œ ์ข…์–‘์˜ ์ฆ์‹๊ณผ ์นจ์œค์— ์ค‘์š”ํ•œ ์ธ์ž๋กœ ์ž‘์šฉํ•  ์ˆ˜ ์žˆ๊ณ , ํ™˜์ž์˜ ์˜ˆํ›„์™€ ์ƒ์กด๊ธฐ๊ฐ„์— ํ•„์ˆ˜์ ์ธ ์—ญํ• ์„ ํ•œ๋‹ค๊ณ  ์˜ˆ์ธก ํ•  ์ˆ˜ ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋ฏ€๋กœ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ๊ต๋ชจ์„ธํฌ์ข…์˜ ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰์— ์žˆ์–ด pY705STAT3์™€ CXCR4์˜ ๋ฐœํ˜„์ด ๊ฐ€์ง€๋Š” ์—ฐ๊ด€์„ฑ์„ ๋ฐํžˆ๊ณ ์ž ํ•˜์˜€๋‹ค. pY705STAT3์˜ ๋†’์€ ๋ฐœํ˜„์„ ๊ฐ€์ง€๋Š” ๊ต๋ชจ์„ธํฌ์ข… 1์ฐจ ๋ฐฐ์–‘์„ธํฌ๋Š” CXCR4๋ฅผ ๋†’๊ฒŒ ๋ฐœํ˜„ํ•˜์˜€์œผ๋ฉฐ, ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰๊ณผ ์นจ์œค์ด ์ฆ๊ฐ€๋œ ์–‘์ƒ์„ ๋ณด์˜€๋‹ค. pY705STAT3์™€ CXCR4 ๋ฐœํ˜„์˜ ์ค‘์š”์„ฑ์„ ์ฆ๋ช…ํ•˜๊ธฐ ์œ„ํ•ด CXCR4 ๋ฐœํ˜„์„ ์–ต์ œ์‹œ์ผฐ๊ณ , ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰๊ณผ ์นจ์œค์ด ๊ฐ์†Œ๋˜๋Š” ์–‘์ƒ์„ ํ™•์ธ ํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋ฐ˜๋ฉด pY705STAT3์˜ ๋‚ฎ์€ ๋ฐœํ˜„์„ ๊ฐ€์ง€๋Š” ๊ต๋ชจ์„ธํฌ์ข… 1์ฐจ ๋ฐฐ์–‘์„ธํฌ์— CXCR4๋ฅผ ๊ณผ๋ฐœํ˜„ ์‹œํ‚ด์œผ๋กœ์จ ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰๊ณผ ์นจ์œค์ด ์ฆ๊ฐ€ ๋จ์„ ํ™•์ธ ํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ํฅ๋ฏธ๋กญ๊ฒŒ๋„, STAT3๋ฅผ ๊ณผ๋ฐœํ˜„ ์‹œ์ผฐ์„ ๋•Œ CXCR4์˜ ๋ฐœํ˜„์ด ์ฆ๊ฐ€ ๋  ๋ฟ ์•„๋‹ˆ๋ผ, CXCR4๋ฅผ ๊ณผ๋ฐœํ˜„ ์‹œ์ผฐ์„ ๋•Œ์—๋„ STAT3์˜ ๋ฐœํ˜„์ด ์ฆ๊ฐ€ ๋˜์—ˆ๋‹ค. ๋”์šฑ์ด STAT3์™€ CXCR4๋Š” ์„œ๋กœ ๊ฒฐํ•ฉํ•˜๊ณ  ์žˆ์Œ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๊ณ , ์ด๋Š” ๋‘ ๋‹จ๋ฐฑ์งˆ์ด ์ƒํ˜ธ์ž‘์šฉ์„ ํ†ตํ•ด ์„œ๋กœ๋ฅผ ์กฐ์ ˆํ•œ๋‹ค๊ณ  ์˜ˆ์ธก ํ•  ์ˆ˜ ์žˆ๋‹ค. ์ด๋Ÿฌํ•œ ๊ฒฐ๊ณผ๋“ค์„ ์ข…ํ•ฉํ•˜๋ฉด, STAT3๊ฐ€ ๋†’๊ฒŒ ๋ฐœํ˜„ ๋˜์–ด์žˆ๋Š” ๊ต๋ชจ์„ธํฌ์ข…์€ CXCR4๋ฅผ ๊ฐ•ํ•˜๊ฒŒ ๋ฐœํ˜„ํ•˜๋ฉฐ, ์ด๋“ค์˜ ๋ฐœํ˜„ ์ •๋„๋Š” ์•”์„ธํฌ์˜ ์นจ์œค์„ฑ์™€ ๋ฐ€์ ‘ํ•œ ์ƒ๊ด€๊ด€๊ณ„๊ฐ€ ์žˆ์Œ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋ฅผ ๊ธฐ๋ฐ˜์œผ๋กœ STAT3์™€ CXCR4์˜ ๋†’์€ ๋ฐœํ˜„์€ ์ƒํ”ผ์ค‘๊ฐ„์—ฝ์„ธํฌ์ดํ–‰ ํ˜„์ƒ์„ ํ†ตํ•ด ์นจ์œค๋Šฅ๋ ฅ์„ ์ฆ๊ฐ€์‹œํ‚จ๋‹ค๋Š” ๊ฒฐ๊ณผ์— ๋„๋‹ฌํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๊ทธ๋Ÿฌ๋ฏ€๋กœ STAT3์™€ CXCR4๋Š” ์•…์„ฑ์˜ ๋‡Œ ์•”์—์„œ ์ค‘์š”ํ•œ ์น˜๋ฃŒ์  ํƒ€๊นƒ์ด ๋  ์ˆ˜ ์žˆ์„ ๊ฒƒ์ด๋‹ค.Glioblastoma is a highly invasive and aggressive brain malignancy. Despite significant improvements in early diagnosis and treatments of primary brain tumors, still many patients with malignant glioblastoma will survive less than one year after diagnosis from aggressive progression and recurrence. Although the exact causes or the mechanism beneath are not clear yet but there is certainly an increase of interest in the correlation between progression of glioblastoma and of its STAT3 and CXCR4 expression. STAT3 is associated with proliferation of glioblastoma stem cells. Recent study reported that CXCR4 is a chemokine receptor known to mediate glioma cell invasiveness. According to these reports, I could predict that STAT3 and CXCR4 are the important factors to not only aggressiveness and invasiveness but also survival period of patients in glioblastoma. Thus this study aims to investigate the association between invasion, migration and Epithelial-Mesenchymal transition of glioblastoma with pY705STAT3 and CXCR4 expression. The primary glioblastoma cells with high pY705STAT3 level overexpress CXCR4, resulting in enhanced EMT and migration in vitro. CXCR4 silencing reduced the EMT and migration of primary glioblastoma cells. In contrast the primary GBL cells that have low pY705STAT3 level hardly express CXCR4, resulting in reduced EMT and migration. Moreover, CXCR4 was regulated by STAT3 from the fact that STAT3 overexpression lead to increase level of CXCR4 expression in GBL cells. Even more interesting is the CXCR4 overexpression can up-regulate STAT3 expression in GBL cell and STAT3 directly interacts with CXCR4. Taken together STAT3 derepressed glioblastoma expressed CXCR4 robustly and demonstrated a correlative relationship between expression levels of the CXCR4 and aggressiveness of the cells. My findings suggest that STAT3 related CXCR4 expression enhances EMT phenomenon and invasive potential of GBL cells. Therefore, STAT3 and CXCR4 expression status may be a useful potential therapeutic target in malignant brain tumor.ABSTRACT i CONTENTS iv LIST OF FIGURES v LIST OF ABBREVIATIONS vi INTRODUCTION 1 MATERIAL AND METHOD 5 RESULT 12 DISCUSSION 35 REFERENCES 37 ABSTRACT IN KOREAN 43 Fig 1. Character comparison on pY705STAT3 expression in glioblastoma primary cells 19 Fig 2. The comparison of prognosis in patients withThe comparison of prognosis in patients with glioblastoma according to the difference of phosphorylated STAT3 expression 21 Fig 3. CXCR4 expression in GBL primary cells 23 Fig 4. pY705 STAT3 expression enhances aggressiveness in glioblastoma 25 Fig 5. STAT3 and CXCR4 can induce EMT in vitro 27 Fig 6. STAT3 and CXCR4 promote cell migration in vitro 30 Figure 7. STAT3 interacts with CXCR4 33Maste

    ์••์šด๊ณผ ์žฅ๋ฒ•์˜ ์ƒ๊ด€์„ฑ ๊ณ ์ฐฐ -ๆœ่ฉฉ๋ฅผ ์ค‘์‹ฌ์œผ๋กœ-

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    ๊ทผ์ฒด์‹œ๋Š” ํ•œ ้Ÿป์„ ์ฒ˜์Œ๋ถ€ํ„ฐ ๋๊นŒ์ง€ ์‚ฌ์šฉํ•˜๊ณ  ๆ›้Ÿปํ•˜์ง€ ์•Š๋Š”๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์••์šดํ•˜๋Š” ๊ณณ๋„ ์ •ํ•ด์ ธ ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ๊ทผ์ฒด์‹œ์˜ ์žฅ๋ฒ•์— ์••์šด์€ ์–ด๋– ํ•œ ์—ญํ• ๋„ ํ•  ์ˆ˜๊ฐ€ ์—†๋‹ค. ์ด์— ๋ฐ˜ํ•˜์—ฌ ๊ณ ์ฒด์‹œ๋Š” ํ™˜์šด์„ ํ•˜๊ธฐ๋„ ํ•˜๊ณ  ์••์šดํ•˜๋Š” ์œ„์น˜์— ๋ณ€ํ™”๋ฅผ ์ค„ ์ˆ˜๋„ ์žˆ์œผ๋‹ˆ, ์‹œ์ธ์€ ์••์šด์„ ํ†ตํ•˜์—ฌ ์‹œ์ƒ ์ „๊ฐœ์— ์ž์‹ ์˜ ์˜๋„๋ฅผ ๋‹ด์„ ์ˆ˜ ์žˆ๋‹ค. ๋ฐ”๊พธ์–ด ๋งํ•˜๋ฉด ์žฅ๋ฒ•์— ์••์šด์„ ํ™œ์šฉํ•  ์ˆ˜ ์žˆ๊ฒŒ ๋˜๋Š” ๊ฒƒ์ด๋‹ค. ๋‘์‹œ๋Š” ์žฅ๋ฒ•์ด ์—„์ •ํ•œ๋ฐ, ๊ณ ์ฒด์‹œ์˜ ๊ฒฝ์šฐ ์˜๋„ํ•˜๋Š” ์žฅ๋ฒ•์„ ์••์šด์„ ์ด์šฉํ•˜์—ฌ ์ด๋ฃจ์–ด๋‚ด๊ณ  ์žˆ๋‹ค. ๊ฒŒ๋‹ค๊ฐ€ ์‹œ์˜ ํ’๊ฒฉ์ด๋‚˜ ๊ฒฉ๋ฅ ์„ ๊ตฌํ˜„ํ•˜๋Š” ๋ฐ์—๋„ ์••์šด์„ ์ด์šฉํ•˜์˜€๋‹ค. ๋ณธ๊ณ ๋Š” ๋‘๋ณด ๊ณ ์ฒด์‹œ์˜ ์••์šด ์–‘์ƒ์„ ์‚ดํŽด๋ณด๊ณ ์„œ ๊ทธ๊ฒƒ์ด ์žฅ๋ฒ•๊ณผ ์–ด๋– ํ•œ ์ƒ๊ด€์„ฑ์ด ์žˆ๋Š”์ง€๋ฅผ ์ฃผ๋กœ ๋…ผ์˜ํ•  ๊ฒƒ์ด๋‹ค. ์•„์šธ๋Ÿฌ ์••์šด์ด ์‹œ์˜ ํ’๊ฒฉ๊ณผ ๊ฒฉ๋ฅ ์— ์–ด๋–ค ์ž‘์šฉ์„ ํ•˜๋Š”์ง€์— ๋Œ€ํ•ด์„œ๋„ ๊ฒ€ํ† ํ•  ๊ฒƒ์ด๋‹ค

    Short-term effect of air pollution on respiratory disease in Seoul : a case-crossover design.

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    ํ™˜๊ฒฝ๊ด€๋ฆฌํ•™๊ณผ/์„์‚ฌope

    ์ง€๋ฒˆ๊ตฌํš์ž…๋Œ€๊ฒฝ์„ฑ์ •๋„์˜ ์žฌํ˜„ ๋ฐฉ์‹ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๊ณต๊ณผ๋Œ€ํ•™ ๊ฑด์ถ•ํ•™๊ณผ, 2019. 2. Hong, John.์ง€๋„๋Š” ๋ณตํ•ฉ์ ์ธ ์ •์น˜ ๋ฌธํ™”์  ๊ด€๊ณ„๋ฅผ ํ†ตํ•˜์—ฌ ๋งŒ๋“ค์–ด์ง„, ์–ด๋–ค ์ฃผ์žฅ์ด ๋‹ด๊ธด ๊ฒฐ๊ณผ๋ฌผ๋กœ์„œ ์žฌํ˜„๋ฌผ์„ ์ดํ•ดํ•˜๋Š” ํŠน์ •ํ•œ ์‹œ์ ์„ ์ œ๊ณตํ•œ๋‹ค. ์„œ์šธ์˜ ๊ฒฝ์šฐ ์—ญ์‹œ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ ์‚ฌํšŒ ์ •์น˜์  ์ƒํ™ฉ์— ๋”ฐ๋ผ ์ง€๋„ ์ œ์ž‘ ์ฃผ์ฒด์˜ ์ž…์žฅ์ด ๋‹ฌ๋ผ์ง€๋ฉด์„œ ๋„์‹œ๋ฅผ ์žฌํ˜„ํ•˜๋Š” ๋ฐฉ์‹์ด ๋ณ€ํ™”ํ•ด์™”๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์ด๋Ÿฌํ•œ ๊ด€์ ์—์„œ 1936๋…„์— ์ œ์ž‘๋œ ์ง€๋ฒˆ์ž…๊ตฌํš๋Œ€๊ฒฝ์„ฑ์ •๋„(์ดํ•˜ ๋Œ€๊ฒฝ์„ฑ์ •๋„)์˜ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹์— ์ฃผ๋ชฉํ•˜์—ฌ ๋ณธ ์ง€๋„์˜ ๋ฐฐ๊ฒฝ์— ์ž๋ฆฌํ•œ ์ •์น˜ ๋ฌธํ™”์  ์ž…์žฅ์„ ์ถ”์ ํ•˜๊ณ  ๊ทธ ์žฌํ˜„์˜ ์ „๋žต์ด ๊ฐ€์ง€๋Š” ์˜๋ฏธ๋ฅผ ๋ถ„์„ํ•˜๊ณ ์ž ํ•œ๋‹ค. ๋Œ€๊ฒฝ์„ฑ์ •๋„๋Š” ํ•œ๋ฐ˜๋„์˜ ๊ทผ๋Œ€์  ์ธก๋Ÿ‰์ด ์‹œ์ž‘๋œ ๋Œ€ํ•œ์ œ๊ตญ๊ธฐ๋‚˜ ์ผ์ œ๊ฐ•์ ๊ธฐ ์ดˆ๊ธฐ ์ดํ›„๋กœ ์ œ์ž‘๋œ ๋‹ค๋ฅธ ๊ฒฝ์„ฑ(ํ•œ์–‘)์˜ ๋ฏผ๊ฐ„์‹œ๊ฐ€์ง€๋„๋“ค๊ณผ ์ƒ์ดํ•œ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹์„ ๋ณด์ธ๋‹ค. 1910๋…„๋Œ€์— ์‹œํ–‰๋œ ํ† ์ง€์กฐ์‚ฌ์‚ฌ์—…์˜ ๊ฒฐ๊ณผ๋ฌผ๋กœ ์ œ์ž‘๋œ ์ง€์ ์›๋„๋“ค์— ๊ธฐ์ž…๋œ ์ •๋ณด์ธ ํ•„์ง€์„ , ์ง€์ ์„ ์ด ์‹œ๋ฏผ๋“ค์ด ์ผ์ƒ์ ์œผ๋กœ ์‚ฌ์šฉํ•˜๋Š” ์ง€๋„์— ๋“ฑ์žฅํ•œ ํ˜„์žฌ๊นŒ์ง€ ๋ฐœ๊ฒฌ๋œ ์ฒซ ์‚ฌ๋ก€์ด๋‹ค. ๊ทธ ์ดํ›„๋กœ ๊ฐ™์€ ์žฌํ˜„ ๋ฐฉ์‹์œผ๋กœ ์ œ์ž‘๋œ ์ง€๋„๋Š” ํ•ด๋ฐฉ ํ›„ 1960๋…„๋Œ€์— ์ด๋ฅด๋Ÿฌ์„œ์•ผ ๋“ฑ์žฅํ•˜๊ฒŒ ๋œ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ๋Œ€๊ฒฝ์„ฑ์ •๋„์˜ ์žฌํ˜„ ๋ฐฉ์‹์„ ๋ถ„์„ํ•˜๊ธฐ์— ์•ž์„œ ๋จผ์ € ๊ทผ๋Œ€์  ์ธก๋Ÿ‰์ด ์ฒซ ์‹œํ–‰๋œ ์ผ์ œ๊ฐ•์ ๊ธฐ๋ผ๋Š” ์‹œ๋Œ€์  ์ƒํ™ฉ์„ ๊ณ ๋ คํ•˜์—ฌ ๋จผ์ € ์ง€๋„์˜ ๋„์‹œ ์žฌํ˜„ ๋ถ„์„์„ ๋‘๊ฐ€์ง€ ๋ฐฉํ–ฅ์—์„œ ์ง„ํ–‰ํ•˜์˜€๋‹ค. ๋จผ์ € ๊ทผ๋Œ€์  ์ธก๋Ÿ‰ ๋ฐฉ์‹์ด ์ „๊ตญ์ ์œผ๋กœ ์ฒ˜์Œ ์‹œํ–‰๋˜๊ณ , ์ธก๋Ÿ‰๋„์ธ ์ง€ํ˜•๋„์™€ ์ง€์ ๋„๊ฐ€ ์ œ์ž‘๋˜๊ธฐ ์‹œ์ž‘ํ•œ ์‹œ๊ธฐ์ž„์„ ๊ณ ๋ คํ•˜์—ฌ ์ง€๋„ํ•™ ๋‚ด์  ์š”์ธ์œผ๋กœ ์ธํ•œ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹์˜ ๋ณ€ํ™”๋ฅผ ๋ถ„์„ํ•œ๋‹ค. ์ƒˆ๋กœ์šด ์ธก๋Ÿ‰์ด๋‚˜, ์ƒˆ๋กœ์šด ํ† ์ง€ ๊ด€๋ จ ๋ฒ•๋ น ์ œ์ •์œผ๋กœ ๊ธฐ์กด์— ์กด์žฌํ•˜์ง€ ์•Š๋˜ ๋„์‹œ ์ •๋ณด๊ฐ€ ๋ฏผ๊ฐ„์‹œ๊ฐ€์ง€๋„์— ๋“ฑ์žฅํ•œ๋‹ค. ๋‘๋ฒˆ์งธ๋กœ๋Š” ๋ฏผ๊ฐ„ ์‹œ๊ฐ€์ง€๋„์˜ ์ œ์ž‘์— ์žˆ์–ด์„œ ์ธก๋Ÿ‰์— ์˜ํ•˜์—ฌ ์ƒ์‚ฐ๋œ ๋„์‹œ ์ •๋ณด์˜ ์„ ํƒ๊ณผ ์žฌ๊ฐ€๊ณต์— ์˜ํ–ฅ์„ ๋ผ์น˜๋Š” ์ •์น˜ ๋ฌธํ™”์  ์••๋ ฅ, ์ง€๋„ํ•™ ์™ธ์  ์š”์ธ์œผ๋กœ ์ธํ•œ ๋ฏผ๊ฐ„ ์‹œ๊ฐ€์ง€๋„๋“ค์˜ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹ ๋ณ€ํ™”๋ฅผ ๋ถ„์„ํ•œ๋‹ค. ์ด๋Ÿฌํ•œ ๋ถ„์„์˜ ํ‹€์„ ๊ฐ€์ง€๊ณ  ๋จผ์ € ๊ฒฝ์„ฑ์˜ ์ธก๋Ÿ‰ ์—ฐ๋ณด์™€ ์ง€ํ˜•๋„์™€ ์ง€์ ๋„์˜ ์ œ์ž‘ ์—ฐ๋ณด๋ฅผ ์‚ดํŽด๋ณด๊ณ , ์ง€๋„ํ•™ ๋‚ด์  ์š”์ธ์˜ ์˜ํ–ฅ์œผ๋กœ ์ธํ•œ ์ง€๋„ ์—ฐ๊ตฌ ๋ฒ”์ฃผ ์‹œ๊ธฐ ๋‚ด์˜ ๋ฏผ๊ฐ„ ์‹œ๊ฐ€์ง€๋„๋“ค์˜ ๋ณ€ํ™” ์–‘์ƒ์„ ๋ถ„์„ํ•˜์˜€๋‹ค. ์ด๋Š” ๋Œ€๊ฒฝ์„ฑ์ •๋„์˜ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹์ด ์ง€๋„ํ•™ ์™ธ์  ์š”์ธ์— ์˜ํ•œ ๋ณ€ํ™”๋ผ๋Š” ๊ฒƒ์„ ํ™•์ธํ•˜๊ธฐ ์œ„ํ•œ ์„ ํ–‰ ์ž‘์—…์ด์—ˆ์œผ๋ฉฐ, ์ด๋ฅผ ํ†ตํ•ด ๋ฏผ๊ฐ„ ์‹œ๊ฐ€์ง€๋„์˜ ์—ฐ๋ณด ์†์—์„œ ๋Œ€๊ฒฝ์„ฑ์ •๋„๊ฐ€ ์ง€๋‹ˆ๋Š” ์˜๋ฏธ๋ฅผ ๋„์ถœํ•ด๋‚ด์—ˆ๋‹ค. ๋Œ€๊ฒฝ์„ฑ์ •๋„์— ๊ธฐ์ž…๋œ ์ง€์ ์„ ์ด๋ผ๋Š” ํ† ์ง€ ์ •๋ณด์˜ ๊ฒฝ์šฐ ์ •๋ณด์˜ ์ €๋ณธ์ด ๋˜๋Š” ์ง€์ ๋„๊ฐ€ 1910๋…„๋Œ€์— ์ด๋ฏธ ์ œ์ž‘๋˜์—ˆ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ , 1936๋…„์ด ๋˜์–ด์„œ์•ผ ์‹œ๊ฐ€์ง€๋„์˜ ์ œ์ž‘์ž์— ์˜ํ•˜์—ฌ ์„ ํƒ๋˜๊ณ , ์žฌ๊ฐ€๊ณต๋˜์—ˆ๋‹ค๋Š” ์ ์—์„œ ๋Œ€๊ฒฝ์„ฑ์ •๋„๊ฐ€ ๋ณด์—ฌ์ฃผ๋Š” ๋ณ€ํ™”๋Š” ์ง€๋„ํ•™ ์™ธ์  ์š”์ธ์— ์˜ํ•˜์—ฌ ๋ฐœ์ƒํ•œ ์žฌํ˜„ ๋ฐฉ์‹์˜ ๋ณ€ํ™”๋กœ ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์ด๋Š” 1930๋…„๋Œ€์˜ ์ฆ๊ฐ€ํ•œ ๊ฑด์ถ•ํ™œ๋™๊ณผ ํ† ์ง€ ๊ฑฐ๋ž˜ ์ฆ๊ฐ€, ๋„์‹œ์˜ ํ™•์žฅ์œผ๋กœ ์ธํ•œ ๋„์‹œ๋ฅผ ์ดํ•ดํ•˜๋Š” ๋ฐ์— ์žˆ์–ด ํ•„์ง€๋ผ๋Š” ๋งค๊ฐœ์ฒด์˜ ์ค‘์š”์„ฑ์ด ์ฆ๊ฐ€ํ•œ ๊ฒฐ๊ณผ๋กœ ํ•ด์„๋œ๋‹ค.A map as a situated representation is a result of complex political and cultural assertions. Even if not explicit, they reproduce ideological content that provides specific cognitive frames through which the reader understands a version of reality. In this way, representational methods reflected in historical maps of Seoul demonstrate a changing ideological position in regards to the object of the city and its socio-cultural structures. This paper investigates the differing cartographical methodologies of Seoul from the late Joseon period to the 1970s industrialization era, in correlation with the political and cultural shifts of each period, further arguing that the maps have been produced with ideological influence throughout the city's history. Particularly these maps show direct influence from emerging concepts of urban planning manifested through the numerous modifications caused by the rapidly changing political and cultural motives of different subjects. Taking maps of late Joseon dynasty as an analytical vantage point, a methodological shift first appears at the beginning of the 1910s to the mid-1920s. As the Japanese Empire transformed the city to visualize colonial power, the city becomes reinvented as a dialectic of the existing urban fabric and the colonial style architecture and road system. This perception of the city results in the Gyeongseong sigado produced in the mid-1920s. Subsequently, the other major shift appears in the mid-1930s following the implementation of Act of Chosun City Planning, the first modern urban planning act on the Korean peninsula. This new pragmatic discourse focused on the expansion and efficiency of the city changed the priority of representation from the former visualization constitutive interest to the administration constitutive interest. As a concrete strategy of expansion and functionalization, the land rearrangement project based on a development logic of Tabula Rasa urbanism also gave influence to the shift: Rather than depict what was already existing, the policy prioritized an emptying of the city ground plane to create a more predictable future. This methodological tendency is highly evident in the policys main map, the Daegyeongsung jeongdo, created in 1936. Finally, the paper concludes that the mapping of Seoul has stabilized after the 1960s industrialization and modernization period, with an emphasis on repetitive and pragmatic urban planning strategies that reflect an ideological logic of intensive expansion, development, and redevelopment.1. ์„œ ๋ก  . 1 1.1. ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ๊ณผ ๋ชฉ์  1 1.2. ์—ฐ๊ตฌ์˜ ๋ฐฉ๋ฒ• ๋ฐ ๋ฒ”์œ„ 6 2. ์„œ์šธ ์ธก๋Ÿ‰๊ณผ ๋„์‹œ ์ •๋ณด์˜ ์ƒ์‚ฐ 12 2.1. ์ง€ํ˜• ์ธก๋Ÿ‰: ๋ฌผ๋ฆฌ ์ •๋ณด ์žฌํ˜„์˜ ์—ญ์‚ฌ 12 2.2. ์ง€์  ์ธก๋Ÿ‰: ํ† ์ง€ ์ •๋ณด ์žฌํ˜„์˜ ์—ญ์‚ฌ 24 3. ๋„์‹œ ์ •๋ณด์˜ ํ™•์‚ฐ๊ณผ ์‹œ๊ฐ€์ง€๋„์—์˜ ์˜ํ–ฅ 28 3.1. ํ† ์ง€ ์กฐ์‚ฌ ์‚ฌ์—… ์ด์ „์˜ ๊ฒฝ์„ฑ ์‹œ๊ฐ€์ง€๋„ 28 3.2. ํ† ์ง€ ์กฐ์‚ฌ ์‚ฌ์—… ์ดํ›„์˜ ๊ฒฝ์„ฑ ์‹œ๊ฐ€์ง€๋„ 34 3.3. ์ง€๋ฒˆ๊ตฌํš์ž…๋Œ€๊ฒฝ์„ฑ์ •๋„์˜ ์ œ์ž‘ . 42 4. ๋Œ€๊ฒฝ์„ฑ์ •๋„์˜ ๋„์‹œ ์žฌํ˜„ ๋ฐฉ์‹๊ณผ ์ด๋ฐ์˜ฌ๋กœ๊ธฐ . 49 4.1. ์ง€์ ์„ ์œผ๋กœ ์žฌํ˜„๋œ ๋„์‹œ 49 4.2. ์ด๋ฐ์˜ฌ๋กœ๊ธฐ์™€ ์žฌํ˜„ ๋ฐฉ์‹์˜ ๋ฐ˜๋ณต 52 5. ๊ฒฐ ๋ก  . 55 ์ฐธ๊ณ ๋ฌธํ—Œ 57Maste
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