• Title/Summary/Keyword: Target region

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Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells

  • Yong-Kyu Lee;Hyeon Ho Heo;Nackhyoung Kim;Ui-Hyun Park;Hyesook Youn;Eun-Yi Moon;Eun-Joo Kim;Soo-Jong Um
    • BMB Reports
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    • v.57 no.6
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    • pp.299-304
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    • 2024
  • Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activation-mediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells.

Conceptional design of an adjustable moderator for BNCT based on a neutron source of 2.8 MeV proton bombarding with Li target

  • Yinan Zhu;Zuokang Lin;Haiyan Yu;Xiaohan Yu;Zhimin Dai
    • Nuclear Engineering and Technology
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    • v.56 no.5
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    • pp.1813-1821
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    • 2024
  • Beam shaping assembly (BSA) is a vital component in Boron Neutron Capture Therapy (BNCT) for obtaining epithermal neutron beams. Several feasible designs of BSA for accelerator-based BNCT (AB-BNCT) neutron source are carried out based on neutrons by bombarding a natural lithium target with 10 mA, 2.8 MeV proton beams. The calculation results demonstrate that a thickness of 45 cm is appropriate for general moderators referring to the therapeutic parameter of Advanced Depth (AD). A series of optimizations are performed and two results are confirmed: One is that employing the configuration of MgF2 and FLUENTAL combined by 1:1 could improve the therapeutic rate (TR) of tumors at a depth of middle region, and the other one is that the TR of superficial tumors can be increased by adding a 5 cm thick boron-11 secondary moderator at the end of general moderators. As a result, an innovative conception of an adjustable moderator is recommended to BNCT. Compared to the MgF2 moderator with a fixed thickness of 45 cm, the TR value can be improved by a maximum of 47.7 % by using the adjustable moderator. Furthermore, the configuration of adjustable moderator has been designed with regulation method for treating tumors of different depths.

An Efficient Image Retrieval Method Using Informations for Location and Direction of Outdoor Images (outdoor image의 촬영 위치와 방향 정보를 이용한 효율적인 영상 검색방법)

  • Han, Gi-Tae;Suh, Chang-Duk
    • The KIPS Transactions:PartB
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    • v.14B no.5
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    • pp.329-336
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    • 2007
  • In this paper we propose both the construction of image DB including information on the shooting location and direction of the captured outdoor images and the efficient retrieval method from the DB. Furthermore, for the automatic extraction of the location and direction information, we suggest to have the Digital Camera equipped with an expandable GPS modulo which has a function to calculate the location and direction and also to utilize GPS IFD tags in the EXIF. Then that will make it possible for us to retrieve quickly and precisely the target image with its geography and other objects on the ground included. In the previous retrieval method based only on the location, we eel some extra useless images due to the fact that all the images in the ROI(Region Of Interest) are searched on one condition, radius. However, with the proposed method in this paper, we can not only retrieve all the images selectively within the ROI but also achieve nearly 100% of precision when we search for the target images within DOI(Direction Of Interest) with another condition, direction, added. Applying this method to an image retrieval system, we can classify or retrieve natural images based on the location and direction information, which, in turn, will be vitally useful to diverse industrial fields such as disaster alarm system, fire and disaster prevention system, traffic information system, and so forth.

Temporal and Spatial Variation and Characteristics of Ambient Air Quality in Urban Areas in Gyeonggi Province (경기도 도시지역 환경대기질의 시공간적 추이와 특성)

  • Kim, Jong-Chan
    • Journal of Environmental Health Sciences
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    • v.38 no.3
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    • pp.269-276
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    • 2012
  • Objectives: The purpose of this study was to provide policy directions for air pollution reduction by analyzing the variation in the characteristics of air contaminants around the Gyeonggi Province area. Methods: The data used in the study was obtained from air quality monitoring stations operated by the Gyeonggi Provincial Government. The target area was the air quality management area of the Gyeonggi Province region. Results: The concentration of $PM_{10}$ (particles measuring $10{\mu}m$ or less) in 2009 was $60{\mu}g/m^3$, which has been reduced by about 2.7% per year after improvement countermeasures were emplaced. The air pollution control policy was especially more effective for coarse particulate matter (CPM, $PM_{10-2.5}$). The improvement of $NO_2$ pollution was generally very low, especially in cities which had considerable automobile traffic. The concentration of $SO_2$ pollution was rapidly improved in industrial areas, but did not show any difference for multiple and general cities. The predicted concentration of $PM_{10}$ for 2014 based on the trend over 2001-2009 was $53.4{\mu}g/m^3$, which fails to meet the target concentration of $40{\mu}g/m^3$. The predicted concentration of $NO_2$ shows a very low probability of achieving the target concentration of 22 ppb, and thus the current improvement of air quality has proven unsatisfactory. Conclusion: Air pollution control policy should be enforced according to regional pollution characteristics in order to obtain maximum effectiveness in improvement.

Construction of Recombinant Bombyx mori Nuclear Polyhedrosis Virus Using a FLP/FRT System of Yeast, Saccharomyces cerevisiae 2$\mu$m plasmid (Yeast의 FLP/FRT 시스템을 이용한 BmNPV의 유전자 재조합)

  • 강석우;윤은영
    • Journal of Sericultural and Entomological Science
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    • v.40 no.1
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    • pp.52-59
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    • 1998
  • For the construction of plasmid and bmNPV sarrying the FRT recognition site for the FLP recombinases, we synthesized the wild type FRT dligonucleotides. The target FRT sequences consist of three 13bp repeated DNA sequences; two repeats in a direct orientation and one inverted relative to the other two. In addition, there is an 8bp spacer region between the repeats which determune the orientation of the FRT recombination site. In order to place the FRT site both in target BmNPV genome and the transfer vector, we constructed a plasmid, FRT site both in the target BmNPv genome and the transfer vector, we constructed a plasmid, pFRT$\beta$-gal, carrying the FRT sites within the cloning sites of pSV vector and a recombinant BmNPV, vFRTPH, carrying the FRT sites at a downstream of polyhedrin promotor, respectively. In order to test the functionality of the FLP/FRT site-specific recombination system, vFRTPH, pFRT$\beta$-gal and pHsFLP DNA were co-transfected into BmN-4 cells. The resulting recombinant virus was designated a vFRT$\beta$2-gal. From construction analysis of the vFRT$\beta$2-gal with PCR technique it was concluded that the entire pFRT$\beta$-gal plasmid with $\beta$-galactosidase gene and origines of replication flanked by two functional hybrid FRT sequences. The efficiency of recombination was 8.7%, which was higher than that(2.2%) of recombination between a conventional transfer vector and the wild type BmNPV.

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Development of the Passive Outside Insulation Composite Panel for Energy Self-Sufficiency of Building in the Region (지역 건축물의 에너지 자립을 위한 패시브 외단열 복합패널 개발 연구)

  • Moon, Sun-Wook
    • Journal of the Korean Institute of Rural Architecture
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    • v.20 no.1
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    • pp.11-18
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    • 2018
  • The study aims to address the energy crisis and realize self-sufficiency of building as part of local energy independence, breaking away from a single concentrated energy supply system. It is intended to develop modules of the outside insulation composite panels that conform to passive certification criteria and for site-assembly systematization. The method of study first identifies trends and passive house in literature and advanced research. Second, the target performance for development is set, and the structural material is selected and designed to simulate performance. Third, a test specimen of the passive outside insulation curtain wall module designed is manufactured and constructed to test its heat transmission coefficient, condensation performance and airtightness. Finally, analyze performance test results, and explore and propose ways to improve the estimation and improvement of incomplete causes to achieve the goal. The final test results achieved the target performance of condensation and airtightness, and the heat transmission coefficient was $0.16W/(m^2{\cdot}K)$, which is $0.01W/(m^2{\cdot})K$ below the performance target. As for the lack of performance, we saw a need for a complementary design to account for simulation errors. It also provided an opportunity to recognize that insulated walls with performance can impact performance at small break. Thus, to be commercialized into a product with the need for improvement in the design of the joint parts, a management system is needed to increase the precision in the fabrication process.

Epigenetic Changes within the Promoter Regions of Antigen Processing Machinery Family Genes in Kazakh Primary Esophageal Squamous Cell Carcinoma

  • Sheyhidin, Ilyar;Hasim, Ayshamgul;Zheng, Feng;Ma, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10299-10306
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    • 2015
  • The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

Dosimetric Effects of Air Pocket during Magnetic Resonance-Guided Adaptive Radiation Therapy for Pancreatic Cancer

  • Jin, Hyeongmin;Kim, Dong-Yun;Park, Jong Min;Kang, Hyun-Cheol;Chie, Eui Kyu;An, Hyun Joon
    • Progress in Medical Physics
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    • v.30 no.4
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    • pp.104-111
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    • 2019
  • Purpose: Online magnetic resonance-guided adaptive radiotherapy (MRgART), an emerging technique, is used to address the change in anatomical structures, such as treatment target region, during the treatment period. However, the electron density map used for dose calculation differs from that for daily treatment, owing to the variation in organ location and, notably, air pockets. In this study, we evaluate the dosimetric effect of electron density override on air pockets during online ART for pancreatic cancer cases. Methods: Five pancreatic cancer patients, who were treated with MRgART at the Seoul National University Hospital, were enrolled in the study. Intensity modulated radiation therapy plans were generated for each patient with 60Co beams on a ViewrayTM system, with a 45 Gy prescription dose for stereotactic body radiation therapy. During the treatment, the electron density map was modified based on the daily MR image. We recalculated the dose distribution on the plan, and the dosimetric parameters were obtained from the dose volume histograms of the planning target volume (PTV) and organs at risk. Results: The average dose difference in the PTV was 0.86Gy, and the observed difference at the maximum dose was up to 2.07 Gy. The variation in air pockets during treatment resulted in an under- or overdose in the PTV. Conclusions: We recommend the re-contouring of the air pockets to deliver an accurate radiation dose to the target in MRgART, even though it is a time-consuming method.

Analysis of Local Correlation between Shear Wave Velocity and Geo-layer in Korea (국내 지역성을 고려한 전단파속도와 대표지층의 상관관계 분석)

  • Kim, Han-Saem;Choi, Seung-Ho;Chung, Choong-Ki
    • Proceedings of the Korean Geotechical Society Conference
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    • 2010.03a
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    • pp.687-698
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    • 2010
  • Borehole drilled depend on the point is bound to be limited to obtain the 2-D or 3-D layer information for entire targer area. On the other hand, SASW and MASW provide the sectional form of layer information through the shear wave velocity($V_s$). Therefore the useful information of the target area can be derived from SASW, MASW and borehole data. In this research, the correlation reflected locality and nationwide between sectional geo-layer and $V_s$ was investigated and analyzed. The target areas are westside of Pyeongtaek and Incheon. The shear wave velocity($V_s$) obtained from SASW, MASW and borehole data conducted within the scope of crossline for survey was utilized in each region. In the 2D distribution of $V_s$ from SASW, MASW, $V_s$ tend to continually increase deeper and deeper. By the target area, the depth of each representative geo-layer was nested on the sectional distribution map of $V_s$ to suggest the range of $V_s$ in accordance of strata by using borehole data. The 2D sectional geo-layer distribution map is presented based on the range of $V_s$. In addition the correlation between measured and calculated $V_s$ according to the empirical equation was analyzed.

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Identification of Caenorhabditis elegans MicroRNA Targets Using a Kernel Method

  • Lee, Wha-Jin;Nam, Jin-Wu;Kim, Sung-Kyu;Zhang, Byoung-Tak
    • Genomics & Informatics
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    • v.3 no.1
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    • pp.15-23
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    • 2005
  • Background MicroRNAs (miRNAs) are a class of noncoding RNAs found in various organisms such as plants and mammals. However, most of the mRNAs regulated by miRNAs are unknown. Furthermore, miRNA targets in genomes cannot be identified by standard sequence comparison since their complementarity to the target sequence is imperfect in general. In this paper, we propose a kernel-based method for the efficient prediction of miRNA targets. To help in distinguishing the false positives from potentially valid targets, we elucidate the features common in experimentally confirmed targets. Results The performance of our prediction method was evaluated by five-fold cross-validation. Our method showed 0.64 and 0.98 in sensitivity and in specificity, respectively. Also, the proposed method reduced the number of false positives by half compared with TargetScan. We investigated the effect of feature sets on the classification of miRNA targets. Finally, we predicted miRNA targets for several miRNAs in the Caenorhabditis elegans (C. elegans) 3' untranslated region (3' UTR) database. Condusions The targets predicted by the suggested method will help in validating more miRNA targets and ultimately in revealing the role of small RNAs in the regulation of genomes. Our algorithm for miRNA target site detection will be able to be improved by additional experimental­knowledge. Also, the increase of the number of confirmed targets is expected to reveal general structural features that can be used to improve their detection.