• Title/Summary/Keyword: contrast flow

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Silencing of Suppressor of Cytokine Signaling-3 due to Methylation Results in Phosphorylation of STAT3 in Imatinib Resistant BCR-ABL Positive Chronic Myeloid Leukemia Cells

  • Al-Jamal, Hamid AN;Jusoh, Siti Asmaa Mat;Yong, Ang Cheng;Asan, Jamaruddin Mat;Hassan, Rosline;Johan, Muhammad Farid
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4555-4561
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    • 2014
  • Background: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib. Materials and Methods: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and $IC_{50}$ values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting. Results: The $IC_{50}$ for imatinib on K562 was 362nM compared to 3,952nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down-regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562. Conclusions: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

Studies on the Positive Inotropic Mechanism of Aconiti Tuber (부자 강심성분의 작용기전에 관한 연구)

  • Kim Myung-Suk;Kim Yong-Sik
    • The Korean Journal of Pharmacology
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    • v.17 no.1 s.28
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    • pp.9-15
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    • 1981
  • Aconiti tuber butanol fraction, which is isolated from the chloroform insoluble and water soluble extract of Aconitum volubile, has been recently known to have a potent positive inotropic effect in the isolated cardiac muscle preparations of various animals. The positive inotropic mechanism of Aconiti tuber butanol fraction, in relation with the external calcium, was studied using the isolated cat papillary muscle. The positive inotropic effect was dependent on the calcium concentration in the nutrient medium, and a synergistic relation could be demonstrated between Aconiti tuber butanol fraction and the external calcium. The inotropic effect of $10^{-4}g/ml$ of Aconiti tuber butanol fraction was equivalent to that of 0.06mM of calcium in the medium. After the treatment with a calcium influx inhibitor, Verapamil$(2{\pm}10^{-7}-10^{-6}M)$, the contractile force of the papillary muscle was markedly inhibited. In these preparations, Aconiti tuber butanol fraction restored the decreased contractility in a dose-dependent manner. It was suggested that the positive inotropic effect of Aconiti tuber butanol fraction might be related with the stimulating action on the calcium influx through the slow inward calcium channels in the cardiac cell membrane. In contrast with digitalis cardiac glycoside, Aconiti tuber butanol fraction infused intravenously into the anesthetized rabbit decreased the systemic arterial blood pressure and increased the carotid blood flow, but produced no prominent changes in the heart rate.

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Long-term Performance of Stock Splits (주식분할의 장기성과)

  • Byun, Jong-Cook;Jo, Jeong-Il
    • The Korean Journal of Financial Management
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    • v.24 no.1
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    • pp.1-27
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    • 2007
  • In this study, we investigated the market long-term performance of stock splits by using the Korean Stock Market data from 1998 through 2002. We measured the performance by the event-time portfolio approach with the buy-and-hold abnormal return(BHAR) and the cumulative average abnormal return(CAAR). Also, the calendar-time portfolio approach with one-factor and three factor model were used for avoiding the misspecification model problem. The first of main results in this study was that the stock splits had significantly positive abnormal returns around the month of the stock splits announcements. However, the period BHAR and CAAR after the announcement month were significantly negative. This negative long-term abnormal returns were confirmed by the calendar-time portfolio approach. The results suggested that the abnormal return followed by the stock splits seemed to be positive in the short-term period. Second, there was no the difference of the long term performance between the high and the low split ratios. The operating income performance in the periods followed by the stock splits announcements grew worse. Therefore, the signalling effects, the managers of the firm under considering the stock splits would make use of splits as a form of signals for the upward changes in the cash flow or profits, could not be found. Finally, in contrast to Fama, Fisher, Jensen and Roll(1969), the significant negative abnormal returns following the stock splits were still found irrespective of the change of dividend payout ratio.

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Power Optimization of Organic Rankine-cycle System with Low-Temperature Heat Source Using HFC-134a (저온 열원 HFC-134a 유기랭킨사이클의 출력 극대화)

  • Baik, Young-Jin;Kim, Min-Sung;Chang, Ki-Chang;Lee, Young-Soo;Ra, Ho-Sang
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.35 no.1
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    • pp.53-60
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    • 2011
  • In this study, an organic Rankine-cycle system using HFC-134a, which is a power cycle corresponding to a low-temperature heat source, such as that for geothermal power generation, was investigated from the view point of power optimization. In contrast to conventional approaches, the heat transfer and pressure drop characteristics of the working fluid within the heat exchangers were taken into account by using a discretized heat exchanger model. The inlet flow rates and temperatures of both the heat source and the heat sink were fixed. The total heat transfer area was fixed, whereas the heat-exchanger areas of the evaporator and the condenser were allocated to maximize the power output. The power was optimized on the basis of three design parameters. The optimal combination of parameters that can maximize power output was determined on the basis of the results of the study. The results also indicate that the evaporation process has to be optimized to increase the power output.

T1-weighted MR Imaging of the Neonatal Brain at 3.0 Tesla: Comparison of Spin Echo, Fast Inversion Recovery, and Magnetization-prepared Three Dimensional Gradient Echo Techniques (3T 자기공명영상 장비에서 신생아 뇌의 T1 강조 영상: 스핀에코, 고속 역전회복, 자기화 삼차원 경사에코기법의 비교)

  • Jeong, Jee-Young;Yoo, So-Young;Jang, Kyung-Mi;Eo, Hong;Lee, Jung-Hee;Kim, Ji-Hye
    • Investigative Magnetic Resonance Imaging
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    • v.11 no.2
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    • pp.87-94
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    • 2007
  • Purpose: The purpose of this study was to evaluate the usefulness of fast inversion recovery (FIR) and magnetization-prepared three dimensional gradient echo sequence (3D GRE) T1-weighted sequences for neonatal brain imaging compared with spin echo (SE) sequence in a 3T MR unit. Materials and Methods: T1-weighted axial SE, FIR and 3D GRE sequences were evaluated from 3T brain MR imaging in 20 neonates. The signal-to-noise ratio (SNR) of different tissues was measured and contrast-to-noise ratios (CNR) were determined and compared in each of the sequences. Visual analysis was carried out by grading gray-white matter differentiation, myelination, and artifacts. The Wilcoxon signed ranked test was used for evaluation of the statistical significance of CNR differences between the sequences. Results: Among the three sequences, the 3D GRE had the best SNRs. CNRs obtained with FIR and 3D GRE were statistically superior to those obtained with SE; these CNRs were better on the 3D GRE compared to the FIR. Gray to white matter differentiation and myelination were better delineated on the FIR and 3D GRE than the SE. However, motion artifacts were more commonly observed on the 3D GRE and flow-related artifacts of vessels were frequently seen on the FIR. Conclusion: FIR and 3D GRE are valuable alternative T1-weighted sequences to conventional SE imaging of the neonatal brain at 3T providing superior image quality.

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Occurrences of Hot Spring and Potential for Epithermal Type Mineralization in Main Ethiopian Rift Valley (주 에티오피아 열곡대 내 온천수의 산출특성 및 천열수형 광상의 부존 잠재성)

  • Moon, Dong-Hyeok;Kim, Eui-Jun;Koh, Sang-Mo
    • Economic and Environmental Geology
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    • v.46 no.3
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    • pp.267-278
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    • 2013
  • The East African Rift System(EARS) is known to be hosted epithermal Au-Ag deposits, and the best-known example is Main Ethiopian Rift Valley(MER) related to Quaternary bimodal volcanism. Large horst-graben system during rifting provides open space for emplacement of bimodal magmas and flow channel of geothermal fluids. In recent, large hydrothermally altered zones(Shala, Langano, and Allalobeda) and hot spring related to deeply circulating geothermal water have been increasing their importance due to new discoveries in MER and Danakil depression. The hot springs in Shala and Allalobeda occur as boiling pool and geyser on the surface, whereas some areas didn't observe them due to decreasing ground water table. The host rocks are altered to quartz, kaolinite, illite, smectite, and chlorite due to interaction with rising geothermal water. The hot springs in MER are neutral to slightly alkaline pH(7.88~8.83) and mostly classified into $HCO_3{^-}$ type geothermal water. They are strongly depleted in Au, and Ag, but show a higher Se concentration of up to 26.7 ppm. In contrast, siliceous altered rocks around hot springs are strongly enriched in Pb(up to 33 ppm, Shala), Zn(up to 313 ppm, Shala), Cu(up to 53.1 ppm, Demaegona), and Mn(up to 0.18 wt%t, Shala). In conclusion, anomalous Se in hot spring water, Pb, Zn, Cu, and Mn in siliceous altered rocks, and new discoveries in MER have been increasing potential for epithermal gold mineralization.

A Neurobiological Measure of General Intelligence in the Gifted (뇌기능영상 측정법을 이용한 영재성 평가의 타당성 연구)

  • Cho, Sun-Hee;Kim, Heui-Baik;Choi, Yu-Yong;Chae, Jeong-Ho;Lee, Kun-Ho
    • Journal of Gifted/Talented Education
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    • v.15 no.2
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    • pp.101-125
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    • 2005
  • We applied functional magnetic resonance imaging (fMRI) techniques to examine whether general intelligence (g) could be assessed using a neurobiological signal of the brain. Participants were students in a national science academy and several local high schools. They were administered diverse intelligence (RAPM and WAIS) and creativity tests (TTCT-figural and TTCT-verbal). Forty of them were scanned using fMRI while performing complex and simple g tasks. In brain regions of greater blood flow in complex compared with simple g tasks, the gifted group with an exceptional g level was not significantly different from the average group with an ordinary g level: both of them activated the lateral prefrontal, anterior cingulate, posterior parietal cortices. However, the activation levels of the gifted group were greater than those of the average group, particularly in the posterior parietal cortex. Correlation analysis showed that the activity of the posterior parietal cortex has the highest correlation ($(r=0.73{\sim}0.74)$) with individual g levels and other regions also have moderate correlation ($(r=0.53{\sim}0.66)$). On the other hand, two-sample t test showed a striking contrast in intelligence tests scores between the gifted and the average group, whereas it did not show in creativity tests scores. These results suggest that it is within the bounds of possibility that a neurobiological signal of the brain is used in the assessment of the gifted and also suggest that creativity has to be given a great deal of weight on the assessment of the gifted.

Effects of tktA, $aroF^{FBR}$and aroL Expression in the Tryptophan-Producing Escherichia coli

  • Kim, Tae-Hyun;Namgoong, Suk;Kwak, Joon-Hyeok;Lee, Se-Yong;Lee, Heung-Shick
    • Journal of Microbiology and Biotechnology
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    • v.10 no.6
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    • pp.789-796
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    • 2000
  • In order to analyze the effects of tktA, $aroF^{FBR}$, and aroL expression in a tryptophan-producing Escherichia coli, a series of plasmids carrying the genes were constructed. Introduction of tktA, $aroF^{FBR}$, and aroL into the E. coli strain resulted in approximately 10-20 fold increase in the activities of transketolase, the feedback inhibition-resistant 3-deoxy-D-arabinoheptulsonate-7-phosphate synthase, and shikimate kinase. Expression of $aroF^{FBR}$ in the aroB mutant strain of E. coli resulted in the accumulation of 10 mM of 3-deoxy-D-arabinoheptulsonate-7-phosphate (DAHP) in the medium. Simultaneous expression of tktA and $aroF^{FBR}$ in the strain further increased the amount of excreted DAHP to 20 mM. In contrast, the mutant strain which has no gene introduced accumulated 0.5 mM of DAHP. However, the expression of tktA and $aroF^{FBR}$ in a tryptophan-producing E. coli strain did not lead to the increased production of tryptophan, but instead, a significant amount of shikimate, which is an intermediate in the tryptophan biosynthetic pathway, was excreted to the growth medium. Despite the fact that additional expression of shikimate kinase in the strain could possibly remove 90% of excreted shikimate to 0.1 mM, the amount of tryptophan produced was still unchanged. Removing shikimate using a cloned aroL gene caused the excretion of glutamate, which suggests disturbed central carbon metabolism. However, when cultivated in a complex medium, the strain expressing tktA, $aroF^{FBR}$, and aroL produced more tryptophan than the parental strain. These data indicate that additional rate-limiting steps are present in the tryptophan biosynthetic pathway, and the carbon flow to the terminal pathway is strictly regulated. Expressing tktA in E. coli cells appeared to impose a great metabolic burden to the cells as evidenced by retarded cell growth in the defined medium. Recombinant E. coli strains harboring plasmids which carry the tktA gene showed a tendency to segregate their plasmids almost completely within 24h.

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Seismic AVO Analysis, AVO Modeling, AVO Inversion for understanding the gas-hydrate structure (가스 하이드레이트 부존층의 구조파악을 위한 탄성파 AVO 분석 AVO모델링, AVO역산)

  • Kim Gun-Duk;Chung Bu-Heung
    • 한국신재생에너지학회:학술대회논문집
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    • 2005.06a
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    • pp.643-646
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    • 2005
  • The gas hydrate exploration using seismic reflection data, the detection of BSR(Bottom Simulating Reflector) on the seismic section is the most important work flow because the BSR have been interpreted as being formed at the base of a gas hydrate zone. Usually, BSR has some dominant qualitative characteristics on seismic section i.e. Wavelet phase reversal compare to sea bottom signal, Parallel layer with sea bottom, Strong amplitude, Masking phenomenon above the BSR, Cross bedding with other geological layer. Even though a BSR can be selected on seismic section with these guidance, it is not enough to conform as being true BSR. Some other available methods for verifying the BSR with reliable analysis quantitatively i.e. Interval velocity analysis, AVO(Amplitude Variation with Offset)analysis etc. Usually, AVO analysis can be divided by three main parts. The first part is AVO analysis, the second is AVO modeling and the last is AVO inversion. AVO analysis is unique method for detecting the free gas zone on seismic section directly. Therefore it can be a kind of useful analysis method for discriminating true BSR, which might arise from an Possion ratio contrast between high velocity layer, partially hydrated sediment and low velocity layer, water saturated gas sediment. During the AVO interpretation, as the AVO response can be changed depend upon the water saturation ratio, it is confused to discriminate the AVO response of gas layer from dry layer. In that case, the AVO modeling is necessary to generate synthetic seismogram comparing with real data. It can be available to make conclusions from correspondence or lack of correspondence between the two seismograms. AVO inversion process is the method for driving a geological model by iterative operation that the result ing synthetic seismogram matches to real data seismogram wi thin some tolerance level. AVO inversion is a topic of current research and for now there is no general consensus on how the process should be done or even whether is valid for standard seismic data. Unfortunately, there are no well log data acquired from gas hydrate exploration area in Korea. Instead of that data, well log data and seismic data acquired from gas sand area located nearby the gas hydrate exploration area is used to AVO analysis, As the results of AVO modeling, type III AVO anomaly confirmed on the gas sand layer. The Castagna's equation constant value for estimating the S-wave velocity are evaluated as A=0.86190, B=-3845.14431 respectively and water saturation ratio is $50\%$. To calculate the reflection coefficient of synthetic seismogram, the Zoeppritz equation is used. For AVO inversion process, the dataset provided by Hampson-Rushell CO. is used.

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Climatological Boundary and Characteristics of Coastal Zone over the Southwestern Korean peninsula (한반도 남서해안의 기후학적 연안지대의 경계와 특징)

  • 이영선;하경자;전은희
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.9 no.3
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    • pp.137-152
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    • 2004
  • The climatological characteristics of coastal zone over the southwestern coast of Korea peninsula were investigated using the data observed by AWS (automatic weather system) and 4 buoy points. Coastal zone is climatologically defined as the region bounded by the distinct contrast of temperature gradient and wind speed across coastline. In the southwest of peninsula four cross-lines consisted of AWS aligned with each buoy were selected as Geojedo buoy line, Geomundo buoy line, Chilbaldo buoy line and Dukjukdo buoy line. Analysis on the diurnal cycle and intra-month variation, monthly mean and maximum value, the temperature gradient with distance between buoy and each station and the accumulative frequency of wind speed were applied to find out the characteristics and the range of coast zone. The maximum ranges of coastal zone vary from offshore to Sanglim (about 34 km distance from coastline) for Geojedo buoy line, to Sunchun (about 52 km) for Geo-mundo buoy line, to Jaeundo (about 27 km) for chilbaldo buoy line and to Yongin (about 65 km) for Dukjukdo buoy line. The modification of coastal zone according to synoptic flow was investigated for the onshore, off-shore and calm cases. The ranges of coastal zone are significantly changed with the distance between 65∼90 km for the case of onshore. In addition, we tried to find out the variation of the wind and temperature and the wind ratio of wind speed at ocean to land stations along Geojedo buoy line during 12∼13 Sep. 2003 affected by typhoon (MAEMI).