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        A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

        Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

        <P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

      • KCI등재
      • KCI등재

        벼, 콩 및 채소류에 대한 Mn-54, Co-60, Zn-65, Cs-137의 토양-작물체간 전이계수

        박찬걸,조용우,최용호,김국찬,이창우,이강석,이정호 대한방사선 방어학회 1991 방사선방어학회지 Vol.16 No.2

        벼, 콩, 상치, 당근, 호박의 가식부위에 대하여 몇가지 토양에 있어서 토양-작물체간 Mn-54, Co-60, Zn-65, Cs-137의 전이계수를 포트 재배에 의한 방사성 추적자 흡수실험을 통하여 조사하였다. 핵종간 전이계수는 거의 모든 경우 Zn-65>Mn-54>Cs-137>Co-60의 순이었다. 콩이 벼보다 전반적으로 한 자리 정도 높은 값을 보였고 채소류의 경우에는 대체로 상치에서 가장 높고 호박에서 가장 낮은 값을 보였다. 강산성 토양에서는 약산성 토양에서보다 전이계수가 훨씬 높았다. 본 조사결과에 입각하여 한국인의 섭식경로 피폭선량 평가에 이용하기 위한 각 핵종의 전이계수치가 작물별로 제안되었다. Soil-to plant transfer coefficients of Mn-54, Co-60, Zn-65 and Cs-137 were estimated for the edible parts of the rice, soybean, lettuce, carrot, and squash grown in different soils by radiotracer uptake experiments using pot cultures. The transfer coefficients of radionuclides were n the order of Zn-65>Mn-54>Cs-137>Co-60 in most of the cases studied. The coefficients for soybean were roughly and order of magnitude higher than those for rice. Among vegetables, lettuce mostly showed the highest value and squash, the lowest. In the strongly acidic soils. From the data obtained, crop-specific transfer coefficients of the four nuclides were proposed for the use in Korean food-radiation dose assessment.

      • STS 304 스테인리스강의 플라즈마 페이스트 침붕처리에 관한 연구

        李聖道,李贊揆,孫明淑,尹在弘,許聖康 國立 昌原大學校 産業技術硏究所 1997 産技硏論文集 Vol.11 No.-

        Various surface properties of boride layer formed by plasma paste boronizing were examined. A boride layer of flat structure was formed on the STS 304 stainless steel substrate by plasma paste boronizing treatment with several different temperature from 1023K to 1223K under gas mixture of Ar/H₂: 2/1(vol.%). The paste was composed of 30wt% boron and 70wt% borax. The properties of boride layer were evaluated by micro vickers hardness tester, SEM, EPMA, and corrosion tester. Metallographic cross section of the borided specimen was consisted of the boride layer, Ni rich layer, Cr rich layer, and matrix structure. It was found to form boride layer in a short time to conventional boronizing methode. In XRD analysis of boride surface, various peaks such as FeB, Ni₃B and CrB were presented. Especially, the peak of CrB was more intensive than other peaks. Activation energy for the formation of boride layer was found to be 123kJ/mol which is lower than the conventional boronizing treatment. The microhardness of these boride layers were in the range of HV 1800∼2000. However, from the results of anodic polarization curve in 1M H₂SO₄solution on the borided specimens, it is found that the corrosion resistance is improved by boronizing treatment. Primary current density is, however, increased with the Boronizing temperature.

      • Back-Propagation Algorithm 상에서의 성능에 미치는 Parameters 분석에 관한 연구

        강수연,박찬호,이현수 慶熙大學校 1994 論文集 Vol.23 No.-

        신경망에서 가장 많이 사용되고 있는 알고리즘 중의 하나가 역전파(Back-Propagation) 알고리즘이다. 역전파 알고리즘에서 문제해결에 본질적인 영향을 주는 몇가지 요인들이 존재한다. 본 연구에서는 이 몇가지 요인들이 각각의 응용 문제의 해를 얻는데 미치는 영향을 시뮬레이션 결과를 통해 알아보고 이를 분석및 고찰 하였다. 고려 대상의 요인들로써는 learning rate, momentum, weight 초기값, 은닉 유니트수를 들 수 있다. 응용 문제 대상은 XOR 문제와 8*8 dot alphanumeric font 학습으로 하였다. Back-Propagation is one of algorithms that are currently used in neural network. It has some factors that basically affect on solving problems. On this paper, we analyze and investigate several learning parameters that effect on solutions of each application problems through simulation result. Considered factors are learning rate, momentum, initial weight values and the number of hidden units. Applied problems are XOR learning and 8*8 dot alphanumeric font learning.

      • 압력센서의 디지털 인터페이스와 신호처리에 관한 연구

        강형구,이종호,안광희,이충호,박찬원 江原大學校 産業技術硏究所 1997 産業技術硏究 Vol.17 No.-

        A smart pressure measurement system is described, which provides a precise A/D conversion and is highly suitable for communication with microprocessors. In order to avoid unstable problems of remote pressure sensing we have developed a new interface board which performs the A/D conversion and smart signal processing of the measured pressure data Serial communication software which is based on ASCII code commands is also developed to process initial setup an calibration functions as well as multi-drop communication with PC. The test and evaluation of the proposed system has been shown as having the better performance compared to the other types of existing pressure measuring systems and will give good applications to the industrial use where a highly precision remote sensing is needed.

      • KCI등재

        액체-고체 순환유동층의 상승관에서 액상의 점도가 고체체류량 및 열전달계수에 미치는 영향

        이찬기,강석환,신광식,송평섭,강용,김상돈 한국화학공학회 2003 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.41 No.4

        직경이 0.102 m이고 높이가 3.5 m인 액체-고체 순환유동층에서 액체의 점도가 고체입자의 체류량과 열전달계수에 미치는 영향을 검토하였다. 밀도가 2,500 kg/㎥인 유리구슬(d_(p)=1.0, 1.7, 2.1 또는 3.0 mm)과 CMC 용액(μ_(L)=0.96-38 mPas)을 각각 고체상과 액체상으로 사용하였다. 액체-고체 순환유동층에서 고체입자의 체류량은 액체의 유속이나 점도가 증가함에 따라 감소하였고 유동입자의 크기나 입자의 순환속도가 증가함에 따라 증가하였다. 액체-고체 순환유동층에서 열전달계수는 액체의 점도가 증가함에 따라 감소하였고 유동입자의 크기나 순환속도가 증가함에 따라 증가하였으나, 액체의 유속이 증가함에 따라서는 큰 변화가 없었다. 액체-고체 순환유동층에서 고체입자의 체류량과 열전달계수는 다음과 같이 실험변수와 무차원군에 의해 상관식으로 얻을 수 있었다. E_(S) = 0.783U^(-0.100)_(L)G^(0.164)_(S)d^(0.302)_(p)μ^(-0.036)_(L) h = 4349.3U^(0.010)_(L)G^(0.099)_(S)d^(0.151)_(p)μ^(-0.015)_(L) ◁그림삽입▷ Effects of liquid viscosity on the solid holdup and heat transfer coefficient have been investigated in the riser of a liquid-solid circulating fluidized beds, whose diameter is 0.102 m and 3.5 m in height. Glass beads (d_(p)=1.0, 1.7, 2.1 or 3.0 ㎜) whose density is 2,500 ㎏/㎥ and aqueous solutions of carboxymethy cellulose (CMC)(μ_(L)=0.96-38 mPas) have been used as the solid and liquid phase, respectively. It has been found that the solid holdup decreases with increasing liquid velocity or viscosity, but it increases with increasing solid particle size or solid circulation rate. The heat transfer coefficient decreases with increasing liquid viscosity but it increases with increasing particle size or solid circulation rate, however, it does not change considerablely with increasing liquid velocity. The solid holdup and heat transfer coefficient have been well correlated in terms of operating variables or dimensionless groups as fellow: ◁수식원문참조▷

      • 항공기 세로운동에 대한 가변구조모델추종제어시스템의 설계에 관한 연구

        李康態,黃壽贊 한국항공대학교 1992 論文集 Vol.30 No.-

        항공기의 세로운동에 대한 가변구조모델추종제어기를설계 하였다. 슬라이딩모드에서 발생하는 채터링의 크기를 최소로 하는 다변수제어 알고리즘을 제시하고 그 타당성을 컴퓨터시뮬레이션을 통하여 보았다. A variable structure model-following controller is designed for the longitudinal motion of an aircraft. The proposed multivariable control law reduces the magnitude of the chattering in sliding mode. Simulation results show the performance of the control system.

      • KCI등재

        TDI계 수분산성 폴리우레탄 접착제의 특성에 Diisocyanate의 구조가 미치는 영향

        강승구,송봉근,이재흥,박찬조,류해일 한국공업화학회 2003 공업화학 Vol.14 No.3

        수년 전부터 많은 연구자들에 의해 폴리우레탄의 수용화, 수분산화의 연구가 수행되어 왔다. 그럼에도 불구하고 폴리우레탄의 특성에 디이소시아네이트가 구조에 미치는 영향에 대한 연구는 많이 진행되지 않았고 또한 미흡한 상태이다. 따라서 번 연구에서는 디이소시아네이트의 형태와 함량 변화에 따른 폴리우레탄의 특성을 연구하였다. 폴리우레1탄 수분산체(PUD)는 poly(tetramethylent ether) glycol (PTMG), isophorone diisocyanate (IPDI), toluene 2,4-diisocyanate (TDI), dimethylol propionic acid (DMPA), trethylamine (TEA) 등을 사용하여 제조하였다. 제조한 폴리우레탄 수분산체(PUD)의 구조를 FT-IR을 이용하여 확인하였다. 폴리우레탄 수분산체의 특성은 DSC, gel permeation chromatography (GPC), particle analyzer, universal testing machine (UTM) 등을 사용하여 측정하였다. 폴리우레탄 수분산체(PHD)에서 입자크기는 IPDI 함량이 증가할수록 작아지는 경향을 나타내었으며, 유리전이온도(Tg)는 IPDI 함량이 증가할수록 조금씩 낮아지는 경향을 나타내었다. 또한, 폴리우레탄 수분산체(PUD)의 접착세기 변화에서는 [NCO]/[OH] 몰비를 1.2로 유지되도록 하면서 합성에 관여하는 [NCO] 양에 해당하는 [TDI]/[IPDI] 몰비를 변화시켜 얻은 폴리우레탄 수분산체의 접착세기는 [TDI][IPDI] 몰비가 50/50일때 좋은 집착세기를 나타내었다. 또한 [NCO]/[OH] 몰비를 1.6으로 일정하게 유지되도록 하고 [TDI]/[IPDI] 몰비를 변화시켜 얻은 폴리우레탄 수분산체의 접착세기는 [TDI]/[IPDI] 몰비가 75/25일 때 좋은 접착세기를 나타내었다. Aqueous polyurethane dispersions (PUD) has been investigated by many researchers for a long time. However, relatively little systematic work has been reported, in detail, on the effect of structure of the diisocyanate on the properties of polyurethane. This work describes the properties of polyurethane in relation to the variation of diisocyanate type and contents. Aqueous polyurethane dispersions (PUD) were prepared from the poly(tetramethylene ether) glycol (PTMG), toluene 2,4-diisocyanate (TDI), isophorone diisocyanate (IPDI), dimethyol propionic acid (DMPA), and triethylamine (TEA). Differential scanning calorimetry (DSC), FT-IR, GPC, universal testing machine (UTM), and particle analyzer were utilized to characterize the physical and mechanical properties of PUD according to diisocyanate type and contents. As the content of IPDI in PUD increased, the particle size decreased. The glass transition temperatures (Tg) of PUT were shifted to a lower temperature as IPDI conent increased. When [NCO]/[OH] mole ratio was 1.2, the adhesion force of PUD shown the best result at [TDI]/[IPDI] mole ratio of 50/50. And, at [NCO]/[OH] mole ratio of 1.2, the adhesion force of PUD was the best when [TDIl/[IPDI] mole ratio was 75/25.

      • 압축력을 받는 결함이 있는 구조물의 주파수 해석

        姜贊泳,柳擇仁,朴鳳賢,李晟熙,韓秉基 弘益大學校 科學技術硏究所 1998 科學技術硏究論文集 Vol.9 No.1

        Vibration analysis of through-the-width-split beams for predicting buckling load is investigated based on Euler-Bernoulli beam theory. In split region, each segment is considered as a solid beam. In this region, recurrence equations relating integration constants for adjacent interior regions are established by satisfying continuity conditions at junctions of interior regions. The results of present study are compared with those of experiment and their results give good agreement with each other. From the result, it was shown that local buckling phenomena could appear in fundamental mode, however, there exists load carrying capacity after this phenomena.

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