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Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis

  • Shibuya, Masabumi
    • BMB Reports
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    • v.39 no.5
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    • pp.469-478
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    • 2006
  • Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-$C{\gamma}$-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

Cytogenetic and Genetic Mutation Features of de novo Acute Myeloid Leukemia in Elderly Chinese Patients

  • Su, Long;Li, Xian;Gao, Su-Jun;Yu, Ping;Liu, Xiao-Liang;Tan, Ye-Hui;Liu, Ying-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.895-898
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    • 2014
  • Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.

Index block mapping for flash memory system (플래쉬 메모리 시스템을 위한 인덱스 블록 매핑)

  • Lee, Jung-Hoon
    • Journal of the Korea Society of Computer and Information
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    • v.15 no.8
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    • pp.23-30
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    • 2010
  • Flash memory is non-volatile and can retain data even after system is powered off. Besides, it has many other features such as fast access speed, low power consumption, attractive shock resistance, small size, and light-weight. As its price decreases and capacity increases, the flash memory is expected to be widely used in consumer electronics, embedded systems, and mobile devices. Flash storage systems generally adopt a software layer, called FTL. In this research, we proposed a new FTL mechanism for overcoming the major drawback of conventional block mapping algorithm. In addition to the block mapping table, a index block mapping table with a small size is used to indicate sector location. The proposed indexed block mapping algorithm by adding a small size. By the simulation result, the proposed FTL provides an enhanced speed than a conventional hybrid mapping algorithm by around 45% in average, and the requirement of mapping memory is also reduced by around 12%.

Differentiation Induction of Dendritic Cell Phenotypes from Human Leukemic Cell Lines

  • Lee, Dae-Heui;Park, Jae-Sun;Eo, Wan-Kyu;Kim, Woo-Mi;Kang, Koo-Il
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.1
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    • pp.79-86
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    • 2001
  • Recent clinical studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (ATRA). However, most patients who receive continuous treatment with ATRA relapse and develop ATRA-resistant leukemia. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we investigated the strategies to overcome ATRA resistance of APL cells by inducing the differentiation of DCs from human leukemic cell lines for the developtment of adoptive immunotherapy. CD83 was used as a mature DC marker in this study and the expression of CD83 mRNA was determined by RT-PCR method. The promyelocytic leukemic cell line HL-60, B lymphoblast cell lines RPMI 7666 and NC-37 could be induced to dendritic cells in vitro. Treatment of HL-60 with phorbol 12-myristate 13-acetate (PMA) resulted in the expression of myeloid-related DC phenotypes, while treatment of RPMI 7666 with fms-like tyrosine kinase 3 ligand (Flt3-ligand, FL) and treatment of NC-37 with PMA and FL led to the expression of lymphoid-related DC phenotypes. In conclusion, myeloid-related DC phenotypes and lymphoid-related DC phenotypes could be generated from HL-60, NC-37 and RPMI 7666 cell lines, respectively. These DC phenotypes can potentially be used to generate antileukemic T cells in vitro for adoptive immunotherapy.

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TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

  • Sun Murray Han;Hye Young Na;Onju Ham;Wanho Choi;Moah Sohn;Seul Hye Ryu;Hyunju In;Ki-Chul Hwang;Chae Gyu Park
    • IMMUNE NETWORK
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    • v.16 no.1
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    • pp.61-74
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    • 2016
  • Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s).

The Situation and the Tasks of UK Rail Privatization, Focusing on after the Hatfield Accident (영국 철도 민영화의 현황 및 과제 (Hatfield사고 이후의 변화를 중심으로))

  • Lee, Yong-Sang
    • Journal of Korean Society of Transportation
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    • v.24 no.2 s.88
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    • pp.91-100
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    • 2006
  • This paper examines the situation and tasks of UK rail privatization, especially focusing on after the Hatfield rail accident. Earlier research which focused on the UK's Privatization had little knowledge of the explanations for recent changes. Moreover they had difficulty making a direct comparison between national rail and the privatized rail. Therefore we aye left without a good explanation which has a comprehensive perspective. I attempt to show the change in the rail privatization Process and its outcome, focusing on after the Hatfield rail accident. This Paper argues that the UK's vail privatization process has a regulatory framework which is too complicated with overlapping responsibilities that brought about inefficiency, increasing costs and a superficial safety regime. Especially the planning of rail and infrastructure maintenance did not come to play an appropriate role. However after 2000, the government took charge of setting the strategy for railways, and the Office of Rail Regulation covered safety performance and cost. explain that these changes present a good opportunity to solve the problem of passing the buck for poor performance. Through the analysis, I find that the passenger rail network is well-suited to deliver long distance business and commuters and that the subsidy from the government is decreasing. However, performance, for example punctuality and reliability. should be improved. Especially the Hatfield rail accident caused a reduction in the satisfaction of passengers. In future. the problems of rising costs and monopoly franchise system should be addressed.

A STUDY ON THE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN TENS10N SIDE OF RAT MOLAR PERIODONTAL LIGAMENT FOLLOWING EXPERIMENTAL TOOTH MOVEMENT (백서 구치의 실험적 치아이동시 견인측 치근막에서 혈관성장인자의 발현에 관한 연구)

  • Lim, Yong-Kyu;Shin, Choon-Shik;Lee, Dong-Ryul
    • The korean journal of orthodontics
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    • v.31 no.1 s.84
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    • pp.121-136
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    • 2001
  • This study was performed to analyse the expression of VEGF and it's receptor(VEGFR) in the tension side of the periodontal ligament following orthodontic tooth movement. Upper first molars of Sprague-Dawley rats were moved medially using closed coil spring for 1, 2, 24 hours and 3, 7, 14 days. H&E staining, immunohistochemical staining and in situ hybridization methods were used to analyse the change of the expression of VEGF and VEGFR. The results from this study were as follows : 1. Following tensional force, periodontal ligament showed elongation of fibers, compression and congestion of vessels and regional hemorrhage. These tissue changes were recovered within 3 days of force application. New bone formation was seen after 3 days of force application and continued for the remaining experimental periods. 2. Following tensional force, VEGF and VEGF mRNA expression was increased in the periodontal ligament cells, osteoblasts and cementoblasts. This change was followed by increased vasculature in the periodontal ligament. 3. After 3 days of tensional force, VEGF and VEGF mRNA expression was confined mainly to the osteopaths and the periodontal ligament cells adjacent to the alveolar bone. After 2 weeks of force application, VEGF and VEGF mRNA expression was reduced to the level of control sample. 4. VEGFRs(Flt-1, Flk-1) showed similar expression pattern and it's expression was mainly seen in the endothelial cells and osteoblasts. Following tensional force VEGFR expression was increased in the endothelial cells and osteoblasts. In conclusion, in the tension side of the penodontal ligament, ligament cells, osteoblast and cementoblast showed increased expression of VEGF & VEGF mRNA. It preceded the increase of vasculature and new bone formation. The increased expression of VEGF mRNA in cementoblast may induce periodontal vessels, which distribute mainly the bone side half of periodontal ligament, grow in the direction of tensional force. Increased expression of VEGFR & VEGFR mRNA not only in endothelial cell but in osteoblast, osteocyte and periodontal cells showed VEGF acts not only in paracrine manner but in autocrine one.

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A Study of Adjustment for Beginning & Ending Points of Climbing Lanes (오르막차로 시.종점 위치의 보정에 관한 연구)

  • 김상윤;오흥운
    • Journal of Korean Society of Transportation
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    • v.24 no.5 s.91
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    • pp.35-44
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    • 2006
  • Acceleration and deceleration curves have been used for design purposes worldwide. The curve in design level has been regarded as an single deterministic curve to be used for design of climb lanes. It should be noted that the curve was originally made using ideal driving truck and that the curve is applied during design based on the assumption of no difference between ideal and real driving conditions. However. observations show that aged vehicles and lazy behavioring drivers nay make lower performance of vehicles than the ideal performance. The present paper provides the results of truck speeds at climbing lanes then probabilistic variation of acceleration and deceleration corves. For these purposes. a study about identification of vehicle makers, and weights for trucks at freeway toll gates and then observation of vehicle-following speed were performed. The 85%ile results obtained were compared with the deterministic performance curves of 180, 200, and 220 Ib/hp. It was identified that the performance of 85%ile results obtained from vehicle-following-speed observations were lower than one from deterministic performance curves. From these results, it may be concluded that at the beginning Point of climbing lanes additional $16.19{\sim}67.94m$ is necessary and that at the end point of climbing lanes $53.12{\sim}103.24m$ of extension is necessary.

Characteristics of organic pollutants in discharged industrial waste in Korea - Focuse on metallic and plastic manufacturing processes and wastewater treatment plants - (국내 사업장 폐기물 중 유기오염물질의 배출특성 연구 - 금속과 플라스틱 제조공정 및 폐수처리시설 중심으로 -)

  • Yeon, Jin-Mo;Kang, Young-Yeul;Kim, Woo-Il;Shin, Sun-Kyoung;Jeong, Seong-Kyeong;Cho, Yoon-A;Kim, Na;Kim, Min-Sun
    • Analytical Science and Technology
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    • v.25 no.6
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    • pp.421-428
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    • 2012
  • In this study, PCDD/PCDFs, PAHs and PCBs in wastes from metal, plastic and wastewater treatment facilities were analyzed. The concentrations of PCDD/PCDFs ranged from 7.37~432.20 ng-TEQ/kg in fly ash, 0.51~855.01 ng-TEQ/kg in incinerated ash and 0.37~385.81 ng-TEQ/kg in dust. Dioxin content was lower, compared to data in foreign countries. PAHs concentration was in the range of 0.0075~2.9225 mg/kg for process sludge and 0.0035~1.6716 mg/kg for wastewater sludge, which satisfied all of the two standards (Nap, Ant, B(a)F:4/0.8, Phen, B(a)A:5/1, Flt:10/2.5, B(a)P:4.5/0.9) of the Marine Environment Management Act. PAHs concentration in process sludge and wastewater sludge were slightly lower than those abroad. According to the analysis of seven types of PCBs (in comparison with the first standard, 0.15 mg/kg), concentration was found in the range of 0.0~0.65 mg/kg, while PCB-52, PCB-101, PCB-138, PCB-153 and PCB-180 isomers were detected in excessive value in some machine oil and hydraulic fluid.

Ex vivo Expansion and Clonal Maintenance of CD34+ Selected Cells from Cord Blood and Peripheral Blood (제대혈 및 말포혈로부터 분리한 CD34 양성 세포의 체외 증폭 및 클론 유지)

  • Kim, Soon Ki;Ghil, Hye Yoon;Song, Sun U.;Choi, Jong Weon;Park, Sang Kyu
    • Clinical and Experimental Pediatrics
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    • v.48 no.8
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    • pp.894-900
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    • 2005
  • Purpose : Because of the unavailability of marrow transplantation, umbilical cord blood (CB) is increasingly being used. We evaluated the potential of ex vivo expansion and clonality in CD34+ cells separated from cord blood source and mobilized peripheral blood (PB) in a serum-free media. Methods : The CD34+ cells, selected from CB and mobilized PB, were expanded with hematopoietic growth factors. They were then cultured for burst-forming units of erythrocytes (BFU-E), colony-forming units of granulocytes and monocytes (CFU-GM) and colony-forming units of megakaryocytes (CFU-Mk) at culture days 0, day 4, day 7, and day 14 with various growth factors. Results : The CB-selected CD34+ cells showed significantly higher total cell expansion than those from the PB at day 7 (2 fold increase than PB). The CB-selected CD34+ cells produced more BFU-E colonies than did the PB on culture at days 7 and at day 14. Also, the CB-selected CD34+ cells produced more CFU-Mk colonies than did the PB on culture at day 4 and at day 7. Conclusion : The ex vivo expansion of the CB cells may be promising in producing total cellular expansion, CFU-Mk and BFU-E compared with PB for 7 to 14 days. The growth factors combination including megakaryocyte growth and development, flt3-ligand and interleukin-3 showed more expansion in the view of total cells and clonal maintenance compared with less combination.