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Overcoming 5-Fu Resistance of Colon Cells through Inhibition of Glut1 by the Specific Inhibitor WZB117

  • Liu, Wei;Fang, Yong;Wang, Xiao-Tong;Liu, Ju;Dan, Xing;Sun, Lu-Lu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7037-7041
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    • 2014
  • Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

Interleukin-18 Synergism with Interleukin-2 in Cytotoxicity and NKG2D Expression of Human Natural Killer Cells

  • Qi, Yuan-Ying;Lu, Chao;Ju, Ying;Wang, Zi-E;Li, Yuan-Tang;Shen, Ya-Juan;Lu, Zhi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7857-7861
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    • 2014
  • Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

Densification of Reaction Bonded Silicon Nitride with the Addition of Fine Si Powder - Effects on the Sinterability and Mechanical Properties

  • Lee, Sea-Hoon;Cho, Chun-Rae;Park, Young-Jo;Ko, Jae-Woong;Kim, Hai-Doo;Lin, Hua-Tay;Becher, Paul
    • Journal of the Korean Ceramic Society
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    • v.50 no.3
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    • pp.218-225
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    • 2013
  • The densification behavior and strength of sintered reaction bonded silicon nitrides (SRBSN) that contain $Lu_2O_3-SiO_2$ additives were improved by the addition of fine Si powder. Dense specimens (relative density: 99.5%) were obtained by gas-pressure sintering (GPS) at $1850^{\circ}C$ through the addition of fine Si. In contrast, the densification of conventional specimens did not complete at $1950^{\circ}C$. The fine Si decreased the onset temperature of shrinkage and increased the shrinkage rate because the additive helped the compaction of green bodies and induced the formation of fine $Si_3N_4$ particles after nitridation and sintering at and above $1600^{\circ}C$. The amount of residual $SiO_2$ within the specimens was not strongly affected by adding fine Si powder because most of the $SiO_2$ layer that had formed on the fine Si particles decomposed during nitridation. The maximum strength and fracture toughness of the specimens were 991 MPa and $8.0MPa{\cdot}m^{1/2}$, respectively.

Quantifying the seismic resilience of two tall buildings designed using Chinese and US Codes

  • Tian, Yuan;Lu, Xiao;Lu, Xinzheng;Li, Mengke;Guan, Hong
    • Earthquakes and Structures
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    • v.11 no.6
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    • pp.925-942
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    • 2016
  • With ongoing development of earthquake engineering research and the lessons learnt from a series of strong earthquakes, the seismic design concept of "resilience" has received much attention. Resilience describes the capability of a structure or a city to recover rapidly after earthquakes or other disasters. As one of the main features of urban constructions, tall buildings have greater impact on the sustainability and resilience of major cities. Therefore, it is important and timely to quantify their seismic resilience. In this work, a quantitative comparison of the seismic resilience of two tall buildings designed according to the Chinese and US seismic design codes was conducted. The prototype building, originally designed according to the US code as part of the Tall Building Initiative (TBI) Project, was redesigned in this work according to the Chinese codes under the same design conditions. Two refined nonlinear finite element (FE) models were established for both cases and their seismic responses were evaluated at different earthquake intensities, including the service level earthquake (SLE), the design-based earthquake (DBE) and the maximum considered earthquake (MCE). In addition, the collapse fragility functions of these two building models were established through incremental dynamic analysis (IDA). Based on the numerical results, the seismic resilience of both models was quantified and compared using the new-generation seismic performance assessment method proposed by FEMA P-58. The outcomes of this study indicate that the seismic resilience of the building according to the Chinese design is slightly better than that according to the US design. The conclusions drawn from this research are expected to guide further in-depth studies on improving the seismic resilience of tall buildings.

Two Maternal Lineages Revealed by Mitochondrial DNA D-loop Sequences in Chinese Native Water Buffaloes (Bubalus bubalis)

  • Lei, Chu-Zhao;Zhang, Wei;Chen, Hong;Lu, Fan;Ge, Qing-Lan;Liu, Ruo-Yu;Dang, Rui-Hua;Yao, Yun-Yi;Yao, Li-Bo;Lu, Zi-Fan;Zhao, Zhong-liang
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.4
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    • pp.471-476
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    • 2007
  • Little is known about the origin and genetic diversity of swamp buffaloes in China. To obtain more knowledge on genetics of the water buffalo in China, the complete mitochondrial D-loop sequences of 30 samples from 6 native types were investigated. The results revealed 12 mitochondrial haplotypes with 50 polymorphic sites. Among these polymorphic sites, there were 49 transitions and 1 transversion. The average nucleotide diversity and haplotype diversity estimated from mtDNA D-loop region in 6 Chinese water buffalo types were 0.00684 and 0.798, respectively, showing rather abundant mitochondrial genetic diversity. The Neighbor-Joining (NJ) tree of mtDNA of Chinese water buffaloes was constructed according to the 12 haplotypes. The NJ tree indicated two lineages being designated lineage A and lineage B, in which lineage A was predominant, and lineage B was at low frequency. The new lineage B was first discovered and defined in 6 Chinese water buffalo types. These results showed that two different maternal lineages were involved in the origin of domestic swamp buffaloes in China and the lineage B was probably an introgression from Southeast Asian buffaloes.

Expression of Ki67 in Papillary Thyroid Microcarcinoma and its Clinical Significance

  • Zhou, Yuan;Jiang, Hong-Gang;Lu, Ning;Lu, Bo-Hao;Chen, Zhi-Heng
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1605-1608
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    • 2015
  • Purpose: To investigate the expression of Ki67 protein in papillary thyroid microcarcinoma(PTMC), and to analyze its clinical significance. Materials and Methods: Ki67 protein expression was evaluated in the tissues of 108 human PTMC and 50 other benign papillary hyperplasia of thyroid specimens using immunohistochemistry. Results: The expression intensity of Ki67 in PTMC and benign papillary hyperplasia of thyroid specimens were $1.45{\pm}1.83%$ and $0.46{\pm}0.46%$.The positive expression rates were 46.3% and 14%. There were significant differences between these two groups (p<0.01). There was no significant variation of the expression intensity and positive expression rates of Ki67 in PTMC with gender, age, position of the tumor and the level of TSH pre-operation (p>0.05), but these parameters varied with tumor size, invasion by membrane and cervical lymph node metastasis (p<0.05 or p<0.01). Conclusions: The expression of Ki67 in PTMC was related to tumor size, invasion by membrane and cervical lymph node metastasis, and could be the important indicator for judging clinical progress and estimating prognosis.

(Searching Effective Network Parameters to Construct Convolutional Neural Networks for Object Detection) (물체 검출 컨벌루션 신경망 설계를 위한 효과적인 네트워크 파라미터 추출)

  • Kim, Nuri;Lee, Donghoon;Oh, Songhwai
    • Journal of KIISE
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    • v.44 no.7
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    • pp.668-673
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    • 2017
  • Deep neural networks have shown remarkable performance in various fields of pattern recognition such as voice recognition, image recognition and object detection. However, underlying mechanisms of the network have not been fully revealed. In this paper, we focused on empirical analysis of the network parameters. The Faster R-CNN(region-based convolutional neural network) was used as a baseline network of our work and three important parameters were analyzed: the dropout ratio which prevents the overfitting of the neural network, the size of the anchor boxes and the activation function. We also compared the performance of dropout and batch normalization. The network performed favorably when the dropout ratio was 0.3 and the size of the anchor box had not shown notable relation to the performance of the network. The result showed that batch normalization can't entirely substitute the dropout method. The used leaky ReLU(rectified linear unit) with a negative domain slope of 0.02 showed comparably good performance.

The distribution characteristics of trace elements of fine ambient particulate in Korea

  • Lim, Jong-Myoung;Lee, Jin-Hong;Kim, Ki-Hyun
    • Analytical Science and Technology
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    • v.18 no.3
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    • pp.241-249
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    • 2005
  • In this study, instrumental neutron activation analysis was used to measure the concentrations of about 30 trace elements in airborne particulate (PM2.5) samples at urban area of Daejeon city located in the southwestern region of Korea. An inspection of the measurement data indicates that the distribution patterns of trace elements could clearly distinguish the elements with their concentrations ranging over five orders of magnitude. The mean values for Lu and Dy were found to be the lowest at values of 0.01 and $0.04ng/m^3$, while those for K and Fe showed the highest value of 671 and $653ng/m^3$, respectively. The results of correlation analysis showed that PM2.5 concentrations can exhibit much more enhanced correlations with the elements of earth crustal components. The results of factor analysis further indicated that there are no more than six factors with statistical significance, which may exert dominant roles in regulating the elemental concentration levels in the study area. Enrichment factor analysis supports explicit interpretation of results found by this factor analysis.

Shear bond strength of zirconia to resin: The effects of specimen preparation and loading procedure

  • Chen, Bingzhuo;Yang, Lu;Lu, Zhicen;Meng, Hongliang;Wu, Xinyi;Chen, Chen;Xie, Haifeng
    • The Journal of Advanced Prosthodontics
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    • v.11 no.6
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    • pp.313-323
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    • 2019
  • PURPOSE. Shear bond strength (SBS) test is the most commonly used method for evaluating resin bond strength of zirconia, but SBS results vary among different studies even when evaluating the same bonding strategy. The purpose of this study was to promote standardization of the SBS test in evaluating zirconia ceramic bonding and to investigate factors that may affect the SBS value of a zirconia/resin cement/composite resin bonding specimen. MATERIALS AND METHODS. The zirconia/resin cement/composite resin bonding specimens were used to simulate loading with a shear force by the three-dimensional finite element (3D FE) modeling, in which stress distribution under uniform/non-uniform load, and different resin cement thickness and different elastic modulus of resin composite were analyzed. In vitro SBS test was also performed to validate the results of 3D FE analysis. RESULTS. The loading flat width was an important affecting factor. 3D FE analysis also showed that differences in resin cement layer thickness and resin composite would lead to the variations of stress accumulation area. The SBS test result showed that the load for preparing a SBS specimen is negatively correlated with the resin cement thickness and positively correlated with SBS values. CONCLUSION. When preparing a SBS specimen for evaluating bond performance, the load flat width, the load applied during cementation, and the different composite resins used affect the SBS results and therefore should be standardized.

Pilot Symbol Assisted Channel Estimation and Equalization for OFDM Systems in Doubly Selective Channels (주파수 선택적 시변 채널 OFDM 시스템에서의 파일럿 심볼을 이용한 채널 예측 및 등화)

  • Lim, Dong-Min
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.18 no.12
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    • pp.1408-1418
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    • 2007
  • In this paper, we analyze the performance of pilot symbol assisted channel estimation and equalization schemes for OFDM systems over frequency-selective time-varying channels and propose methods to improve the system performance. In the least square(LS) and linear minimum mean square error(MMSE) channel estimation, time domain windowing is introduced for banding the frequency domain channel matrix. The linear MMSE and decision feedback equalization schemes are employed with the pilot symbols for channel estimation taken into account in the equalization process. To reduce computational complexity, the band LU matrix factorization algorithm is introduced in solving the linear systems involved in the equalization, and the performances are compared with the known previous results by computer simulations. When time domain windowing is employed in the decision feedback equalization, the matrix related with the decision feedback process is shown to be unhanded and the resultant performance degradation is analyzed.