69 research outputs found
The approach of Healthcare Infrastructure Public-Private Partnership (PPP) in Developing Countries: for the equal good to Korea Interest Group and the Recipient Country
Over the past decade, Public-Private Partnerships (PPPs) have increasingly found their application in the sector of health infrastructure. The objective of this paper is to determine whether PPPs are a viable option for health infrastructure projects in developing countries. For this purpose, the author discusses and describes PPPs in general and specifies features of PPPs, which may be relevant for the healthcare sector and developing countries. In the next step, the author analyses PPP projects that are operating and projects that the author had involved and establishes key learnings from the undertaking. The combined evidence suggests that the PPP model for health infrastructure projects in developing countries can be highly risky for the countries, but also it possesses great insecurity for the participant entities. The author concludes PPP is not a better alternative to ODA in health infrastructure development in developing countries, but it should be an option. Also, the author suggests three conditions, those are prioritizing countries to build partnerships, secure evidence of partner countryโs commitment, testify project design through multiple steps for both the public and the private to successfully use PPP for better health delivery.open์
Analysis of Random Telegraph Noise after Soft Breakdown in the Gate Induced Drain Leakage Current
ํ์๋
ผ๋ฌธ (์์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ์ ๊ธฐยท์ปดํจํฐ๊ณตํ๋ถ, 2013. 8. ์ ํ์ฒ .A Random Telegraph Noise (RTN) in leakage current has been important for discovering the cause of Variable Retention Time (VRT) in Dynamic Random Access Memory (DRAM) cell transistor. Among the several leakage currents, random telegraph noise in Gate Induced Drain Leakage (GIDL) current of a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) is believed as the dominant cause of the VRT. Furthermore, the Soft Breakdown (SBD) has long been one of the main issues of the reliability of MOS transistor when the gate oxide layer is thinner than 4-5 nm. After the SBD occurs, the leakage current suddenly jumps without obvious indication of steps as the stress continues. If the gate tunneling current gradually increases to a certain point, then it will become high enough to cease the circuit to function. There have been many analyses about RTN in gate current after SBD, whereas there is few about RTN in GIDL current. Therefore, there is a need to study RTN in GIDL current after SBD.
In this paper, Intrinsic two-level RTN in Gate Induced Drain Leakage (GIDL) RTN in GIDL current after the Soft BreakDown (SBD) by Constant Voltage Stress (CVS) in the gate-drain overlapped region was measured. In order to conduct comparative analysis, we extracted fundamental parameters of the trap, including the time constant, the trap location (xT) and the energy level (ECox-ET), the capture cross section (ฯc) from the measured RTN. After the first SBD, as the stress is continually given, multi-level GIDL RTN was also observed. As a result, we could predict the gate oxide degradation due to the SBD by observing the GIDL RTN after SBD.Abstract i
Contents iii
1. Introduction 1
2. Extraction of Location and Energy Level of Oxide Trap Generated after Soft Breakdown 4
2. 1 Introduction 4
2. 2 Experimetnal 6
2. 3 Model 7
2. 4 Result and Discussion 16
2. 5 Conclusion 28
3. New Equation of Capture Cross Section Involving Tunneling Analysis 30
3. 1 Introduction 30
3. 2 Model and Discussion 31
3. 3 Conclustion 36
4 Conclusion 37
References 39
Abstract in Korean 43Maste
๋ฌธํ์ฌ ๊ด๋ฆฌ์ ๋ํ ์ธ์ง๋ ์ฑ๊ณผ์ ๋ง์กฑ๋์ ๊ดํ ์ฐ๊ตฌ: ์๋น์ค ๊ฐ์น์ธ์์ ์กฐ์ ํจ๊ณผ๋ฅผ ์ค์ฌ์ผ๋ก
ํ์๋
ผ๋ฌธ (์์ฌ)-- ์์ธ๋ํ๊ต ํ์ ๋ํ์ : ํ์ ๋ํ์ ํ์ ํ๊ณผ ์ ์ฑ
ํ ์ ๊ณต, 2016. 2. ๊ธํ์ญ.๋ณธ ์ฐ๊ตฌ์ ๋ชฉ์ ์ ๋ฌธํ์ฌ์ ๋ํ ์ฑ๊ณผ์ธ์๊ณผ ๋ง์กฑ๋๊ฐ์ ๊ด๊ณ๋ฅผ ์ค์ฆ์ ์ผ๋ก ๋ถ์ํ๋๋ฐ ์๋ค. ํนํ ์ด๋ค ๊ด๊ณ๊ฐ ํฅ์ ์๋ค์ด ์ธ์ํ๋ ๋ฌธํ์ฌ์ ๊ฐ์น, ์ฆ ๋ฌธํ์ฌ ๊ด๋ฆฌ๋ฅผ ํตํด ์ ๊ณต๋๋ ์๋น์ค์ ๊ฐ์น๋ฅผ ๊ณ ๋ คํ์ ๋ ์ด๋ป๊ฒ ๋ฌ๋ผ์ง๋์ง ์ดํด๋ณด๊ณ ์ ํ๋ค.
์ง๊ธ๊น์ง ๋ฌธํ์ฌ ์ ์ฑ
์ ์ํ๋ณด์กด์ ์ง์คํ๋ฉด์ ๋ฌธํ์ฌ ์์ฒด๋ง์ ๊ด๋ฆฌ ๋์์ผ๋ก ์ผ์์์ผ๋, ์ต๊ทผ ๋ค์ด ๋ฌธํ์ฌ ํฅ์ ํนํ, ํฅ์ ์ ์
์ฅ์์์ ๋ฌธํ์ฌ ๊ฐ์น ์ธก๋ฉด์ด ๋ถ๊ฐ๋๋ฉด์ ๊ทธ๋ค์ ๋ง์กฑ์ด ๋ฌธํ์ฌ ๊ด๋ฆฌ์ ์ค์ํ ๋์์ด ๋๊ณ ์๋ค. ๋ฌธํ์ฌ ํฅ์ ์ ๋ฐ๋ฅธ ๋ง์กฑ๋๊ฐ ๋์์๋ก ๋ฌธํ์ฌ ๋ณด์กด ๋ฐ ๊ฐ๋ฐ์ ๋ํ ์ ์ฐฉ์ด ํ์ฑ๋๊ณ ์ด๋ฅผ ํตํด ๋ฌธํ์ฌ ๊ด๋ฆฌ ์ ์ฑ
์ ๋ํ ์์ฉ์ฑ ์ ๊ณ ๋ฐ ๋ฌธํ์ฌ ๊ด๋ฆฌ๋ฅผ ์ํ ์๋ฐ์ ๋
ธ๋ ฅ์ด ์ ๋๋ ์ ์๊ธฐ ๋๋ฌธ์ด๋ค.
ํ์ง๋ง ์ด๋ฌํ ์ธ์์ ์ ํ์๋ ๋ถ๊ตฌํ๊ณ ์ค์ ๋ฌธํ์ฌ ํฅ์ ์ ๊ด๋ จํ ํ์ ์ ยท์ ์ฑ
์ ๋
ผ์๋ ํฅ์ ๊ธฐํ์ ํ๋์ ๊ฐ์ ์์ ์ธ ์ธก๋ฉด์ ๊ฒฝ์ฌ๋๋ ๊ฒฝํฅ์ด ์ง๋ค. ๋์ฑ์ด ์๋น์ค์ ๋ํ ๋ง์กฑ ์ฌ๋ถ์ ๊ทธ ์์ค์ ์๋น์๊ฐ ํด๋น ์๋น์ค์ ๋ถ์ฌํ๋ ๊ฐ์น์ธ์์ ๋ฐ๋ผ ๋ฌ๋ผ์ง ์ ์์์ ๊ธฐ์กด ๊ฒฝ์ํ ๋ฑ ๋ค๋ฅธ ํ๋ฌธ๋ถ์ผ์์ ์ผ๋ฐ์ ์ด๋ผ๋ ์ ์ ์ฐฉ์ํด ๋ณธ ์ฐ๊ตฌ๋ ๋ฌธํ์ฌ ํฅ์ ์๋ค์ด ์ธ์ํ๋ ๋ฌธํ์ฌ์ ๊ฐ์น๋ฅผ ๋ช
์์ ์ผ๋ก ๊ณ ๋ คํจ์ผ๋ก์จ ๋ฌธํ์ฌ ํฅ์ ๋ง์กฑ์ ๋ํ ์ดํด๋ฅผ ์ ๊ณ ํ๊ณ ์ ํ๋ค.
์ด๋ฅผ ์ํด ๋ฌธํ์ฌ์ฒญ์์ ์ค์ํ ใ2010 ๋ฌธํ์ ์ฐ ํฅ์ ์คํ ์กฐ์ฌใ ์๋ฃ๋ฅผ ๋ถ์ํ์์ผ๋ฉฐ, ๋ฌธํ์ฌ์ ๋ํด ๊ฐ์ธ์ด ๋ถ์ฌํ๋ ๊ฐ์น๋ฅผ ๋ฐฐ์์ ๊ณต๊ฐ, ์ ์ฒด์ฑ ํ์ธ ๊ณต๊ฐ, ๊ทธ๋ฆฌ๊ณ ๊ด๊ด ๋ฐ ํด์๊ณต๊ฐ์ผ๋ก ๊ตฌ๋ถํ๊ณ ์ด์ ๋ฐ๋ผ ๋ค์ํ ์ฐจ์์ ๋ง์กฑ๋ ์์ค์ ๊ฒํ ํ์๋ค. ๋ถ์๊ฒฐ๊ณผ ์๋น์ค ์ ๋ฌ ์ฐจ์์ ๋ง์กฑ ์์ค์ ๋ฌธํ์ฌ๋ฅผ ๋ฐฐ์์ ๊ณต๊ฐ์ผ๋ก ์ธ์ํ๋ ์ฌ๋๋ค๊ณผ ๊ตญ๊ฐ ์ ์ฒด์ฑ ํ์ธ ๊ณต๊ฐ์ผ๋ก ์ธ์ํ๋ ์ฌ๋๋ค ์ฌ์ด์์ ํต๊ณ์ ์ผ๋ก ์ ์๋ฏธํ ์ฐจ์ด๋ฅผ ๋ณด์ด๊ณ ์์๊ณ , ์ฉ์ด์ฑ ์ฐจ์์ ๋ง์กฑ ์์ค์ ๋ฐฐ์์ ๊ณต๊ฐ์ผ๋ก ์ธ์ํ๋ ์ฌ๋๊ณผ ๊ด๊ด ๋ฐ ํด์ ๊ณต๊ฐ์ผ๋ก ์ธ์ํ๋ ์ฌ๋ ์ฌ์ด์์ ์ ์๋ฏธํ ์ฐจ์ด๊ฐ ๋ฐ์ํ๋ ๊ฒ์ผ๋ก ๋ํ๋ฌ๋ค. ์ฆ, ํฅ์ ์๋ค์ด ๋ฌธํ์ฌ์ ๋ํด ์ด๋ค ๊ฐ์น๋ฅผ ๋ถ์ฌํ๋์ง์ ๋ฐ๋ผ ๋ฌธํ์ฌ ํฅ์ ์ ๋ฐ๋ฅธ ๋ง์กฑ ์์ค๊ณผ ์ฐจ์์ด ๋ค๋ฅด๊ฒ ๋๊ณ ์์์ ํ์ธํ ์ ์์๋ค.์ 1 ์ฅ. ์๋ก 1
์ 1์ ์ฐ๊ตฌ ๋ชฉ์ ๋ฐ ํ์์ฑ 1
์ 2์ ์ฐ๊ตฌ ๋ฒ์์ ๋ฐฉ๋ฒ 4
1. ์ฐ๊ตฌ๋ฒ์ 4
2. ์ฐ๊ตฌ๋ฐฉ๋ฒ 5
์ 2 ์ฅ. ์ด๋ก ์ ๋
ผ์์ ์ ํ์ฐ๊ตฌ ๊ฒํ 6
์ 1์ ์ด๋ก ์ ๋
ผ์ 6
1. ์๋ฏผ๋ง์กฑ๋ 6
1) ๊ฐ๋
๋ฐ ์์ 6
2) ์ฑ๊ณผํ๊ฐ ์๋จ์ผ๋ก์จ ๋ง์กฑ๋ ์กฐ์ฌ์ ์ ์ฉ์ฑ 7
3) ์๋ฏผ๋ง์กฑ๋ ์ธก์ 9
2. ์ ๋ถ์ฑ๊ณผ 14
1) ๊ฐ๋
14
2) ์ ๋ถ์ฑ๊ณผ์ ๊ดํ ๋
ผ์ 14
3) ์ ๋ถ์ฑ๊ณผ์ ์ธก์ 17
์ 2์ ์ ํ์ฐ๊ตฌ ๊ฒํ 18
1. ์ ๋ถ์ฑ๊ณผ์ ๋ง์กฑ๋์ ๊ด๊ณ 18
2. ์ ๋ถ์ฑ๊ณผ์ ๋ง์กฑ๋ ๊ด๊ณ์ ์์ด์ ์๋น์ค ๊ฐ์น์ ์ญํ 21
1) ๋ง์กฑ๋ ์ฐ๊ตฌ์์ ๊ฐ์น ๋ณ์์ ์ญํ 21
2) ๋ฌธํ์ฌ ๊ด๋ฆฌ์ ์์ด์ ๊ฐ์น์ ๊ดํ ๋
ผ์ 23
์ 3์ ์ ํ์ฐ๊ตฌ์ ํ๊ณ 27
์ 3 ์ฅ. ์ฐ๊ตฌ๋ฌธ์ ์ ๊ฐ์ค 29
์ 1์ ์ฐ๊ตฌ๋ฌธ์ 29
์ 2์ ์ฐ๊ตฌ๊ฐ์ค 29
์ 4 ์ฅ. ์ฐ๊ตฌ์ค๊ณ 32
์ 1์ ์ฐ๊ตฌ์๋ฃ 32
1. ๋ถ์์๋ฃ : ๋ฌธํ์ ์ฐ ํฅ์ ์คํ์กฐ์ฌ 32
1) ์กฐ์ฌ ๊ฐ์ 32
2) ๋ฌธํ์ ์ฐ ํฅ์ ์คํ์กฐ์ฌ์ ๋ด์ฉ 33
2. ๋ถ์๋ฒ์ 33
์ 2์ ๋ณ์์ ์กฐ์์ ์ ์ ๋ฐ ์ธก์ 34
1. ์ข
์๋ณ์ 34
1) ์๋น์ค ์ ๋ฌ 35
2) ์ ๋ณด 36
3) ์ฉ์ด์ฑ 36
4) ์น์ ์ฑ 37
2. ๋
๋ฆฝ๋ณ์ : ์ธ์ง๋ ์ฑ๊ณผ 37
3. ์กฐ์ ๋ณ์ : ์๋น์ค์ ๋ํ ๊ฐ์น์ธ์ 38
4. ํต์ ๋ณ์ 38
1) ๊ฐ์ธ์ ์์ธ 38
2) ์ง์ญ์ ์์ธ 39
์ 5 ์ฅ. ์ค์ฆ๊ฒฐ๊ณผ ๋ถ์ 41
์ 1์ ์๋ฃ์ ๋ถ์๋ฐฉ๋ฒ 41
์ 2์ ๊ฒฐ๊ณผ๋ถ์ 42
1. ๊ธฐ์ ํต๊ณ๋๊ณผ ์๊ด๊ด๊ณ ๋ถ์ 42
1) ์ฃผ์ ๋ณ์๋ค์ ๊ธฐ์ ํต๊ณ 42
2) ์๋น์ค ๊ฐ์น์ธ์ ๊ด๋ จ ๊ธฐ์ ํต๊ณ 42
3) ์๊ด๊ด๊ณ ๋ถ์ 47
2. ์ฐ๊ตฌ๊ฐ์ค ๊ฒ์ฆ 48
1) ์ธ์ง๋ ์ฑ๊ณผ์ ๋ง์กฑ๋ ๊ด๊ณ์ ๋ํ ๊ฒ์ฆ 48
2) ์๋น์ค ๊ฐ์น์ธ์์ ์กฐ์ ํจ๊ณผ์ ๋ํ ๊ฒ์ฆ 51
์ 6 ์ฅ. ๊ฒฐ๋ก 60
์ 1์ ์ฐ๊ตฌ๊ฒฐ๊ณผ ์์ฝ 60
์ 2์ ์ฐ๊ตฌ ์์ฌ์ ๊ณผ ํ๊ณ 64
1. ์ฐ๊ตฌ์ ์์ฌ์ 64
2. ์ฐ๊ตฌ์ ํ๊ณ 65
์ฐธ๊ณ ๋ฌธํ 67
๋ถ๋ก 78
[๋ถ๋ก 1] ๊ฐ์ค 2-1 ๋ถ์ ๊ฒฐ๊ณผ : (์ข
์๋ณ์ : ์๋น์ค ์ ๋ฌ ๋ง์กฑ๋) 78
[๋ถ๋ก 2] ๊ฐ์ค 2-2 ๋ถ์ ๊ฒฐ๊ณผ : (์ข
์๋ณ์ : ์ ๋ณด ๋ง์กฑ๋) 81
[๋ถ๋ก 3] ๊ฐ์ค 2-3 ๋ถ์ ๊ฒฐ๊ณผ : (์ข
์๋ณ์ : ์ฉ์ด์ฑ ๋ง์กฑ๋) 84
[๋ถ๋ก 4] ๊ฐ์ค 2-4 ๋ถ์ ๊ฒฐ๊ณผ : (์ข
์๋ณ์ : ์น์ ์ฑ ๋ง์กฑ๋) 87
Abstract 91Maste
Corrosion Resistance of Surface and Cross Section of Al-Mg Films on Steel Sheet Prepared by PVD Method
Steel is one of widely used materials in various industries because of its excellent mechanical properties and low manufacturing costs. However it is highly susceptible to aggressive corrosion environments such as seawater, thus surface protection as coatings is necessary when using it properly.
Aluminium coatings are used for the corrosion protection of ferrous metal for two main reasons. Firstly, aluminium, with its air-formed passive oxide film, forms an effective barrier layer against attacking materials.
Secondly, if the underlying substrate is exposed at, for example, the base of pre-existing defects or corrosion pits, the aluminium coating will afford a degree of sacrificial protection to the substrate.
A drawback of pure aluminium is, nevertheless, that since its corrosion potential is not far removed from that of many steels, it is unable to provide adequate levels of sacrificial protection, particularly under natural exposure conditions. If aluminium is alloyed with small amounts of active metals such as magnesium, its corrosion potential can be reduced, leading to a significant improvement in sacrificial properties. Therefore, Al-Mg alloy coating was studied and Al-Mg films using the physical vapor deposition(PVD) method that is drawing great attention as an alternative to the conventional coating process were also examined. In addition, cutting section is inevitable when using the surface-treated steel sheet, thus galvanic corrosion properties of Al-Mg films were also studied.
In this experiment, Al-Mg films were deposited onto steel substrates using the eco-friendly PVD method under 10 ~ 31 wt.% Mg contents. The total thickness of every specimen was equal to 5ใ. And then heat treatment was conducted at temperature of 400โ for 10 minutes. The material properties of Al-Mg films were investigated by using SEM, GDS and XRD. The corrosion behaviour of the Al-Mg films determined using neutral salt fog test and electrochemical techniques. After the salt spray test, corrosion products were analyzed by SEM, EDS and XRD at the beginning, middle, and end of the test. Non heat treated Al-Mg specimens were analyzed after 48h, 96h, 168h, and heat treated Al-Mg specimens were analyzed after 72h, 168h, 240h.
Based on the results of the immersion and salt spray tests, heat treated Al-Mg films obviously showed good corrosion resistance compared to non-heat treated Al-Mg films. In the salt spray test in a 5% NaCl environment, Al-Mg films containing 31 wt.% Mg had the most excellent corrosion resistance. In case of the immersion test in a 3% NaCl solution, Al-Mg films ranging from 18 to 22 wt.% Mg had the most excellent corrosion resistance. Also the mechanism of anti-corrosion can be obtained by the analysis of Al-Mg film's corrosion products at each stage.
Consequently, the results of these experiments obtained were as follows-. The difference in corrosion properties between the salt spray test and immersion test is considered the density of corrosion products by the difference of oxygen concentration. Therefore, it is needed to apply the method of estimating the corrosion resistance considering the differences according to environmental conditions.
-. It is thought therefore that the property of Al-Mg films can be improved by heat treatment and uniform distribution of intermetallic compounds.์ 1 ์ฅ ์ ๋ก
1.1 ์ฐ๊ตฌ ๋ฐฐ๊ฒฝ ๋ฐ ๋ชฉ์
1.2 ์ฐ๊ตฌ ์งํ ๋ด์ฉ
์ 2 ์ฅ ์ด๋ก ์ ๋ฐฐ๊ฒฝ
2.1 ์ง๊ณต ๋ฐ ํ๋ผ์ฆ๋ง๋ฅผ ์ด์ฉํ ํ๋ฉด์ฒ๋ฆฌ
2.1.1 ํ๋ผ์ฆ๋ง์ ์ ์ ๋ฐ ์ด์ฉ
2.1.2 ํ๋ผ์ฆ๋ง๋ฅผ ์ด์ฉํ ํ๋ฉด์ฒ๋ฆฌ
2.1.3 PVD๋ฒ
2.2 ๋ฐ๋ง์ ์ ์ ๋ฐ ํ์ฑ
2.2.1 ๋ฐ๋ง์ ์ ์ ๋ฐ ํน์ง
2.2.2 ๋ฐ๋ง์ ํ์ฑ
2.3 ๋ด์์ฑ ์ฝํ
๋ง
2.3.1 ๋ถ์์ ์ ๊ธฐํํ์ ๋ฐ์
2.3.2 ๋ด์์ฑ์ ์ํ ๊ธ์ํผ๋ณต์ ๋ถ๋ฅ
์ 3 ์ฅ ์คํ ๋ฐฉ๋ฒ
3.1 ์คํ ์ฅ์น ๋ฐ ๋ฐ๋ง์ ์ ์ ์กฐ๊ฑด
3.1.1 ์คํ ์ฅ์น
3.1.2 ์ํํธ์ ์ค๋น
3.1.3 ๋ง์ ์ ์ ๋ฐ ์ด์ฒ๋ฆฌ
3.2 ์ ์ ๋ง์ ๋ถ์ ๋ฐ ๋ด์์ฑ ํ๊ฐ
3.2.1 ํ๋ฉด ๋ฐ ๋จ๋ฉด์ ๋ชฐํฌ๋ก์ง ๋ถ์
3.2.2 ์กฐ์ฑ๋ถํฌ ๋ถ์
3.2.3 ์ฑ๋ถ ์ ๋ฐ ๊ฒฐ์ ๊ตฌ์กฐ ๋ถ์
3.2.4 ์ ๊ธฐํํ์ ๋ด์์ฑ ํ๊ฐ
์ 4 ์ฅ ์คํ ๊ฒฐ๊ณผ ๋ฐ ๊ณ ์ฐฐ
4.1 ํ๋ก์ธ์ค ์กฐ๊ฑด์ ๋ฐ๋ฅธ Al-Mg ๋ง์ ์ฌ๋ฃํน์ฑ ๋ถ์
4.1.1 ๋ง์ ๋ชฐํฌ๋ก์ง ๋ฐ ์กฐ์ฑ๋ถํฌ ๋ถ์
4.1.2 ์ฑ๋ถ ์ ๋ฐ ๊ฒฐ์ ๊ตฌ์กฐ ๋ถ์
4.2 ํ๋ก์ธ์ค ์กฐ๊ฑด์ ๋ฐ๋ฅธ Al-Mg ๋ง์ ๋ด์์ฑ ํ๊ฐ
4.2.1 Al-Mg ๋ง ํ๋ฉด์ ์ ๊ธฐํํ์ ๋ด์์ฑ ํ๊ฐ
4.2.2 Al-Mg ๋ง ๋จ๋ฉด์ ์ ๊ธฐํํ์ ๋ด์์ฑ ํ๊ฐ
4.3 Al-Mg ๋ง์ ๋ถ์๋ฐฉ์ ํน์ฑ ๊ด๊ณ ๊ณ ์ฐฐ
4.3.1 Al-Mg ๋ง์ ์ฌ๋ฃํน์ฑ๊ณผ ๋ด์์ฑ ๊ด๊ณ ๊ณ ์ฐฐ
4.3.2 ๋ฐฉ์์ ์์์ ์ฒ ์ ์ ๋
น๋ฐ์ ์์ธ ๊ณ ์ฐฐ
์ 5 ์ฅ ๊ฒฐ
์์ํ๋ถ ๋์ค๊ณํต ์ธํฌ์ ์ ๊ธฐ์๋ฆฌํ์ ํ์ฑ์ ์กฐ์ ํ๋ ์ ์์์กด์ฑ K+ ํต๋ก์ ๋ถ์์๋ฌผํ์ ํน์ฑ
ํ์๋
ผ๋ฌธ (๋ฐ์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ํ๋๊ณผ์ ๋๊ณผํ์ ๊ณต, 2014. 8. ๋ฅํ๋.์์ํ๋ถ์ ์กด์ฌํ๋ ๋์ค๊ณํต(hypothalamic paraventricular nucleusPVN)์ ๊ตฌ์กฐ์ ์ผ๋ก ๋๋ ๊ธฐ๋ฅ์ ์ผ๋ก ๊ตฌ๋ณ๋๋ ์ด์ง์ ์ธ ์ธํฌ๋ค๋ก ์ด๋ฃจ์ด์ ธ ์๋ค. ์ด๋ค ์ธํฌ๋ค์ ์ ๊ธฐ์๋ฆฌํ์ ํน์ฑ๊ณผ A-type K+ ์ ๋ฅ(IA)์ ๊ด๋ จ์ฑ์ ์ ์๋ ค์ ธ ์์ง๋ง, ๊ทธ ๋ถ์์ ํน์ฑ์ ๋ํด์๋ ๋ฐํ์ง ๋ฐ๊ฐ ์๋ค. ๋ฐ๋ผ์, ๋ณธ ์ฐ๊ตฌ์์๋ IA๋ฅผ ์ธ์ฝ๋ฉํ๋ ์ ์์์กด์ฑ K+ ํต๋ก(voltage-gated K+ channelKv ํต๋ก)๊ฐ PVN์ ์ ๋ฆฌ์๋ฆฌํ์ ์ธ ํน์ฑ์ ๊ด์ฌํ ๊ฒ์ด๋ผ๊ณ ๊ฐ์ ํ๊ณ , ์ฑ๊ฒฉ์ด ๋ค๋ฅธ ์ธํฌ ํํ(type I, type II)์์์ Kv ํต๋ก ๋ฐํ์ฐจ์ด์, ์ฌ๋ถ์ ์ด๋ ์์คํธ๋ก๊ฒ์ ์ํด ๊ทธ ํ์ฑ์ด ๋ณํํ๋ ๊ต๊ฐ์ ๊ฒฝ์กฐ์ ์ธํฌ์์์ Kv ํต๋ก ๋ฐํ๋ณํ๋ฅผ ์ดํด๋ณด๊ณ ์ ํ์๋ค. PVN์์ ํน์ ์ธํฌ์์์ ๋ถ์์ ์ ๋ณด๋ฅผ ์ป๊ธฐ ์ํด, ๋จ์ผ์ธํฌ ์ญ์ ์ฌ-์คํฉํจ์์ฐ์๋ฐ์๋ฒ(single cell reverse transcription-polymerase chain reactionsingle cell RT-PCR) ๋๋ ๋จ์ผ์ธํฌ ์ค์๊ฐ ์ญ์ ์ฌ-์คํฉํจ์์ฐ์๋ฐ์๋ฒ (single cell real-time RT-PCR)์ ์ค์ํ์๋ค.
๊ทธ ๊ฒฐ๊ณผ, type I, type II ๋ชจ๋์์ ๋ค์ํ Kv ์ฑ๋ subunit๋ค์ ๋ฐํ์ด ๊ด์ฐฐ๋์๋๋ฐ ๊ทธ ์ค, Kv4.2์ Kv4.3์ ๊ทธ ๋ฐํ ์ ๋์ ์์ด์ type II์์๋ณด๋ค type I์์ ์ ์์ ์ผ๋ก ๋๊ฒ ๋ํ๋ฌ๋ค. ๊ต๊ฐ์ ๊ฒฝ์กฐ์ ์ธํฌ์์๋ Kv4.2์ Kv4.3์ ๋ฐํ์ด ๊ด์ฐฐ๋์๋๋ฐ, ์ฌ๋ถ์ ์ ๋ฐ์ ๋ฐ๋ผ ๊ทธ ๋ฐํ์ด ๋ค๋ฅด๊ฒ ์กฐ์ ๋์๋ค. Kv4.2๋ ์ฆ๊ฐ๋๊ณ Kv4.3์ ๊ฐ์๋์๋ค. ๋ฐ๋ฉด ์์คํธ๋ก๊ฒ์ ์ํด์๋ Kv4.2๋ง์ด ์ ํ์ ์ผ๋ก ๊ฐ์๋์์ผ๋ฉฐ Kv4.3์ ๋ณํ๊ฐ ์์๋ค. ๋ํ IA ์ ๊ฐ์๋ ํจ๊ป ๊ด์ฐฐ๋์๋ค. ์ด๋ฌํ ์์คํธ๋ก๊ฒ์ ์ํฅ์ ๋ฐ์ํ๋ ์ ์ด ํน์ด์ ์ผ๋ก ์ ๊ฒ ๋ถํฌ๋์ด ์๋ dorsal cap ์์ญ์์๋ง ๊ด์ฐฐ๋์๋ค.
์์ ์ฐ๊ตฌ๊ฒฐ๊ณผ๋ Kv4.2์ Kv4.3์ด PVN์ type I, type II๋ฅผ ๊ตฌ๋ณํ๊ณ ๊ต๊ฐ์ ๊ฒฝ์กฐ์ ์ธํฌ์ ์ ๊ธฐ์๋ฆฌํ์ ํ์ฑ์ ์กฐ์ ํ๋ ๋ฐ ์ฃผ์ํ๊ฒ ์์ฉํ๋ฉฐ, ์ง๋ณ์ด๋ ํธ๋ฅด๋ชฌ ๋ณํ์ ์ํด ์๋ก ๋
๋ฆฝ์ ์ผ๋ก ์กฐ์ ๋๊ณ ์์์ ๋ณด์ฌ์ค๋ค. ๋ฐ๋ผ์, Kv ํต๋ก๋ ์์จ์ ๊ฒฝ๊ณ์ ๋ด๋ถ๋น๊ณ์ ๊ธฐ๋ฅ ์ด์์ ๋ฐ๋ฅธ PVN์ ์ ๊ฒฝ์ ๋ฌ ๋ณํ์ ์ฐธ์ฌํ๋ ํ๋์ ๊ธฐ์ ์ผ๋ก ์ฌ๊ฒจ์ง๋ค.The hypothalamic paraventricular nucleus (PVN) comprises anatomically and functionally distinct neuronal populations. The A-type K+ current (IA) is involved in their different electrophysiological properties, but the molecular identity responsible for these differences remains unknown. Accordingly, I hypothesized that voltage-gated K+ (Kv) channels encoding IA are molecular components underlying the determination of electrophysiological characteristics, and compared expressions of Kv channel subunits between distinct neuronal populations in the PVN, using single cell analysis (single cell reverse transcription-polymerase chain reaction [RT-PCR] or single cell real-time RT-PCR).
Results revealed that several Kv channel subunits were expressed in type I and type II PVN neurons which are electrophysiologically distinct. However, the expression density of Kv4.2 and Kv4.3 was significantly higher in type I than in type II neurons. These two subunits were also expressed in the presympathetic neurons, which project to the rostral ventrolateral medulla (RVLMPVN-RVLM), but were differentially regulated during heart failure: Kv4.2 was up-regulated whereas Kv4.3 was down-regulated. In contrast, estrogen replacement into ovariectomized female rats down-regulated Kv4.2 mRNA levels, but did not affect Kv4.3 in the PVN-RVLM neurons. Estrogen also diminished IA density. These estrogenic effects occurred specifically in the dorsal cap parvocellular subdivision where vasopressin is remarkably sparse.
Taken together, Kv4.2 and Kv4.3 are important molecular components underlying the determination of electrophysiological characteristics of different cell types and the modulation of neuronal properties of the presympathetic neurons. The finding of the differential and selective regulations of these two subunits under different pathophysiological conditions suggests that Kv4.2 and Kv4.3 play different roles independently of each other in the coordination of responses of the PVN to various types of stimuli.ABSTRACT
CONTENTS
LIST OF FIGURES
LIST OF TABLES
ABBREVIATIONS
BACKGROUND
CHAPTER I
Single cell analysis of Kv channels that determine neuronal types of rat PVN neurons
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS
CHAPTER II
Differential regulation of Kv4 channel subunits in rat presympathetic PVN neurons after myocardial infarction
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS
CHAPTER III
Selective regulation of Kv channels in rat presympathetic PVN neurons by estrogen replacement
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS
CHAPTER IV
Differential distributions of neuropeptides in rat presympathetic PVN neurons
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS
GENERAL CONCLUSIONS
REFERENCES
ABSTRACT IN KOREANDocto
Molecular Testing in Diagnosis of Thyroid Cancer
With increasing prevalence of thyroid nodules, clinicians are increasingly impelled to identify the optimal predictor of thyroid cancer, with the goal of guiding management based on assessed risk. Fine-needle aspiration cytology is the gold standard diagnostic method for thyroid nodules. However, fine-needle aspiration cytology is not perfect and adjuncts which might complement its predictive value are being investigated from several innovative perspectives. For these vigorous efforts, remarkable advances have been achieved in understanding several major biologic areas of thyroid cancer, including the molecular alterations for loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations in thyroid tumorigenesis and pathogenesis. These exciting advances provide unprecedented opportunities for development of molecular-based novel diagnostic and therapeutic strategies for thyroid cancer. The common somatic genetic changes in thyroid cancer of follicular cell origin (RET/PTC, NTRK, RAS, BRAF, PAX8-PPARฮณ) are generally mutually exclusive, with distinct genotypeโhistologic subtype associations of thyroid cancer. Mutation analysis in fine needle aspiration samples has been applied to improve the diagnostic accuracy. In studies regarding gene expression profiling, aberrant gene methylation and miRNA have shown significant progress toward identification of biomarkers that could improve the accuracy of fine needle aspiration cytology in the evaluation of patients with thyroid nodule and prediction of disease aggressiveness. Future clinical trials evaluating the accuracy and cost-effectiveness of applying these biomarkers in the management of thyroid neoplasm should be considered.ope
Coupling of LETM1 up-regulation with oxidative phosphorylation and platelet-derived growth factor receptor signaling via YAP1 transactivation
Persistent cellular proliferation and metabolic reprogramming are essential processes in carcinogenesis. Here, we performed Gene Set Enrichment Analysis (GSEA) and found that that LETM1, a mitochondrial calcium transporter, is associated with cellular growth signals such as platelet-derived growth factor (PDGF) receptor signaling and insulin signaling pathways. These results were then verified by qRT-PCR and immnunoblotting. Mechanistically, up-regulation of LETM1 induced YAP1 nuclear accumulation, increasing the expression of PDGFB, PDGFRB and THBS4. Consistent with this, LETM1 silencing caused loss of YAP1 nuclear signal, decreasing the expression of PDGFB, PDGFRB and THBS4. Immunohistochemical staining consistently indicated a positive association between LETM1 up-regulation, YAP1 nuclear localization and high PDGFB expression. In clinical data analysis, LETM1 up-regulation in thyroid cancer was found to be related to aggressive tumor features such as lymphovascular invasion (LVI, P < 0.001) and lymph node metastasis (LNM, P = 0.011). Multivariate analysis demonstrated that LETM1 up-regulation increases the risk of LVI and LNM (OR = 3.455, 95% CI = 1.537-7.766 and OR = 3.043, 95% CI = 1.282-7.225, respectively). Collectively, these data suggest that up-regulation of LETM1 induces sustained activation of proliferative signaling pathways, such as PDGF signal pathway by AKT induced YAP1 transactivation, resulting in aggressive thyroid cancer phenotypes.ope
Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer
Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide 'A' at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.ope
Long-term oncologic outcomes of papillary thyroid mircrocarcinoma according to the presence of clinically apparent lymph node metastasi: a large retrospective analysis of 5,348 patients
Purpose:
Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC) may reduce the risk of overtreatment of clinically insignificant cancer. However, the absence of predictor for the progression of PTMC resulted in treatment delay and potentially compromising cure of aggressive disease. Therefore, to anticipate potential damage of delayed surgery, we investigated the oncologic outcomes of patients with low-risk PTMC initially eligible for AS except clinically apparent lymph node metastasis (LNM), imitating delayed surgery with neck dissection.
Materials and methods:
A total of 5,348 patients, enrolled between 1987 and 2016, with low-risk PTMC initially eligible for AS were included regardless of LNM. We classified our study patients into two groups: Group I, lobectomy with prophylactic central cervical node dissection; Group II, total thyroidectomy with modified radical neck dissection for LNM. In addition, we investigated the oncological outcomes of patients with second-wave surgery due to lateral lymph node recurrence (Group III, subgroup of Group I).
Results:
Group I showed more favorable clinicopathological characteristics compared with Group II. In Group I, only 29 (0.58%) of 4,927 patients underwent second-wave surgery with neck dissection for lateral lymph node recurrences, whereas in Group II, all 22 (5.23%) of 421 patients underwent second-wave selective node dissection because of nodal recurrence. Disease-free survival rates were significantly different between Groups I and II (P<0.05). Of note, the recurrence rate of Group II was still significantly higher than that of Group III (5.2% vs 0%, respectively; P=0.021). In addition, Kaplan-Mayer survival analysis indicated poor disease-free survival rates in Group II compared with Group III (P<0.05).
Conclusion:
The long-term treatment outcome of PTMC without LNM was favorable even if the recurrence occurs during follow-up period compared with that of PTMC with LNM. It should be noted that AS might be able to cause poor prognosis due to clinically apparent LNM.ope
Dynamic risk stratification in medullary thyroid carcinoma: Single institution experiences
Recently, dynamic risk stratification has been found to be more valuable than static anatomic staging system in nonmedullary thyroid cancer and this strategy has also been accepted in medullary thyroid cancer (MTC). The present study was designed to compare the clinical usefulness of response to initial therapy stratification with a traditional anatomic staging system.From August 1982 to December 2012, a total of 144 MTC patients underwent thyroidectomy in Yonsei University Hospital. Among them, 117 (82.2%) patients with complete clinical data and sustained follow-up were enrolled in this study. Clinicopathological features and surgical outcomes were analyzed by retrospective medical chart review. Mean follow-up duration was 85.78โยฑโ62.51 months.In this study, mean tumor size was 1.94โยฑโ1.40โcm and 22 (18.9%) patients had hereditary MTC; 95 (81.1%) patients had sporadic MTC. Stage I patients had highest probability of excellent response to initial therapy (92.1%). Stage IV patients had highest probability of biochemical and structural incomplete response to initial therapy (57.5% and 30.3%) and lowest probability of excellent response to initial therapy (12.1%). Both response to initial therapy stratification and TNM staging system offered useful prognostic information in this study. The TNM staging system provided risk stratification pertaining to disease-free survival (DFS), disease-specific survival (DSS), and the probability of having no evidence of disease at final outcome, but did not provide risk stratification pertaining to the probability of having biochemical persistent/recurrence disease at final outcome. However, response to initial therapy stratification provided risk stratification pertaining to not only DFS, DSS, and the probability of having no evidence of disease at final outcome but also the probability of having biochemical persistent/recurrence disease at final outcome.In this study, we demonstrated that dynamic risk stratification with adjusted response to initial therapy system can offer more useful prognostic information than anatomic staging system in MTC.ope
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