• Title/Summary/Keyword: CML

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BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

  • Zhu, Xi-Shan;Lin, Zi-Ying;Du, Jing;Cao, Guang-Xin;Liu, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4773-4780
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    • 2014
  • Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

A Five-year Epidemiologic Study of Childhood Leukemia in Busan City, 1996 to 2000 (최근 5년간(1996-2000) 부산지역 소아 백혈병 환자에 대한 역학적 연구)

  • Moon, Jae Hoon;Lee, Soon Yong;Sinn, Jong Beom;Park, Jae Sun;Lee, Young Ho;Lim, Young Tak;Park, Su Eun
    • Clinical and Experimental Pediatrics
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    • v.46 no.10
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    • pp.972-976
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    • 2003
  • Purpose : For the control of childhood leukemia, of which the mortality is still high, the basic data for the incidence has a great importance. The authors analyzed the data from 133 new patients with childhood leukemia between 1996-2000 in Busan, Korea. Methods : The data were obtained from 133 new cases(87 males and 46 females from 0 to 15 years old) of childhood leukemia who were residents of Busan and who were admitted to the 4 university hospitals and 11 general hospitals from 1996 to 2000. Results : The total number of the new childhood leukemia patients was 133 between 1996-2000; the average annual number of new patients was 26.6. The age-and-sex adjusted annual incidence rate (/100,000) was in the range of 2.37-4.53(male 2.47-5.29, female 0.76-3.36) with an average of 3.29 (male 4.05, female 2.43). Age-specific annual incidence rate(/100,000) was 3.78 in the 0-4 year age group, 3.51 in the 5-9 year age group and 3.08 in the 10-14 year age group. Of the major types of childhood leukemia, the distribution of ALL was average 71.4%, of AML 23.3%, and of CML 4.5%. Of the major types of leukemia by age range, ALL showed highest in the 5-9 year age group, while AML in 0-4 and 10-14 year age groups. Sex-ratio(male to female) of major type of leukemia was 1.97 : 1 and 1.21 : 1, in ALL and AML groups, respectively, while all were male in CML. Conclusion : The average age-and-sex adjusted annual incidence rate(/100,000) of childhood leukemia in Busan from 1996 to 2000 was 3.29. Compared to data in related articles, this data suggests a steady increase in the incidence of childhood leukemia in the Busan area over the last 20 years since 1981.

Functionally Integrated Nonsaturating Logic Elements (기능상 집적된 비포화 논리소자)

  • Kim, Wonchan
    • Journal of the Korean Institute of Telematics and Electronics
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    • v.23 no.1
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    • pp.42-45
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    • 1986
  • This paper introduces novel functionally integrated logic elements which are conceptuallized for large scale integrated circuits. Efforts are made to minimize the gate size as well as to reduce the operational voltage, without sacrificing the speed performance of the gates. The process used was a rather conventional collector diffusion isolation(CDI) process. New gate structures are formed by merging several transistors of a gate in the silicon substrate. Thested elements are CML(Current Mode Logic) and EECL (Emitter-to-Emitter Coupled Logic)gates. The obtained experimental results are power-delay product of 6~11pJ and delay time/gate of 1.6~1.8 ns, confirming the possibility of these novel gate structures as a VLSI-candidate.

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다결정 실리콘 Self-align에 의한 바이폴라 트랜지스터의 제작

  • Chae, Sang-Hun;Gu, Jin-Geun;Kim, Jae-Ryeon;Lee, Jin-Hyo
    • ETRI Journal
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    • v.7 no.4
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    • pp.11-14
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    • 1985
  • A polysilicon self-aligned bipolar n-p-n transistor structure is described, which can be used in high speed and high packing density LSI circuits The emitter of this transistor is separated less than $0.4\mum$ with base contact by polysilicon self-align technology. Through all the process, the active region of this device is not damaged. therefore a high performance device is obtained. Using the transistor with $3.0\mum$ design rules, a CML ring oscillator has per-gate minimum propagation delay time of 400 ps at 2.7 mW power consumption condition.

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웹 서비스 코리오그래피의 상호운용성 지원을 위한 XML 언어 개발

  • Lee, Wan;Jeong, Beom-Seok;Park, Jong-Heon
    • 한국경영정보학회:학술대회논문집
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    • 2007.11a
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    • pp.389-394
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    • 2007
  • 웹 서비스가 현재 산업에서 주요한 분산 컴퓨팅 기술로 대두되면서, 그에 따른 연구가 활발히 이루어지고 있다. 특히, 비즈니스 프로세스 관점에서 BPEL4WS (Business Process Execution Language for Web Services)와 같은 오케스트레이션의 연구가 많이 이루어지고 있다. 또한, 웹 서비스의 주요 구성 요소중에 하나인 코리오크래피에 대한 부분은 W3C (World Wide Web Consortium)에서 현재 후보 권고안 수준인 WS-CDL (Web Services Choreography Description Language) 관련 연구가 이루어지고 있다. 이런 가운데 DERI (Digital Enterprise Research Institute)에서 WSMX (Web Services Execution Environment) 기반의 시맨틱 웹 서비스 분야의 코리오 그래피 연구를 시작하였고, 코리오그래피 불일치 (Mismatch)를 개념적으로 해결하는 방안인 프로세스 미디에이션 (Process Mediation)의 연구가 있었다. 이러한 연구들을 바탕으로 서로 다른 WS-CDL 상에서 특정 참여자가 코리오그래피 미디에이션을 하기위해서 개발된 XML 언어 WS-CML (Web Services Choreography Mediation Language)을 본 논문에서 제안한다.

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The Oscillation Frequency of CML-based Multipath Ring Oscillators

  • Song, Sanquan;Kim, Byungsub;Xiong, Wei
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.15 no.6
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    • pp.671-677
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    • 2015
  • A novel phase interpolator (PI) based linear model of multipath ring oscillator (MPRO) is described in this paper. By modeling each delay cell as an ideal summer followed by a single pole RC filter, the oscillation frequency is derived for a 4-stage differential MPRO. It is analytically proved that the oscillation frequency increases with the growth of the forwarding factor ${\alpha}$, which is also confirmed quantitatively through simulation. Based on the proposed model, it is shown that the power to frequency ratio keeps constant as the speed increases. Running at the same speed, a 4-stage MPRO can outperform the corresponding single-stage ring oscillator (SPRO) with 27% power saving, making MPRO with a large forwarding factor ${\alpha}$ an attractive option for lower power applications.

Implementation of a Chart Editing and Display System Based on XML (XML 기반 차트 편집 및 디스플레이 시스템 구현)

  • Yoon, Hyun-Nim;Lee, Yong-Kyu
    • Proceedings of the Korea Information Processing Society Conference
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    • 2000.10a
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    • pp.707-710
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    • 2000
  • 웹의 사용자가 늘어나면서 웹을 통해 정보를 표현하고 제공하는 수단으로 차트의 사용이 많아지고 있다. 그러나 기존의 차트 표현 방법들은 표현 방법과 구입비용 그리고 호환에 대한 문제점들을 갖고 있다. 따라서 된 논문에서는 이를 해결하기 위해 차트 정보를 웹 표준 언어인 XML을 이용하여 쉽게 표현하고 디스플레이 하는 방법을 제시한다. 본 논문에서 정의한 차트 작성 언어인 CML은 기존의 XML 기반 그래픽 표현 애플리케이션의 복잡성과는 달리 막대형, 원형, 선형의 이차원 차트 정보를 간결하게 표현하고 브라우저를 이용하여 디스플레이 할 수 있다. 본 논문에서 정의한 XML 차트 표현은 어느 플랫폼에서도 호환 가능하며 웹 표준에 근거하였으므로 웹에서의 차트 정보의 공유가 가능하다.

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Optimal design of the suspension stiffness in HDD for improving the load/unload performance (램프 로드-언로드 특성 향상을 위한 서스펜션강성 최적설계)

  • 강태식;김태수;이철우
    • Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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    • 2003.11a
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    • pp.898-901
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    • 2003
  • In order to get the drive reliability and low Power-consumption characteristics, most of small form factor HDD has und the load/unload mechanism instead of CSS type. Compared with CSS mechanism, the load/unload system has little opportunity of head/media contact during the disk spin-up and down. However, the load/unload mechanism needs the precise integration technology with slider, suspension, ramp and load/unload velocity, and all of these component s should be designed simultaneously, not an individually. In this paper, we focus the design of the suspension stiffness using the specified ABS design. We use the CML software to calculate the load/unload dynamic and use the RSM(Response surface method) to get the optimal condition of the suspension stiffness.

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Automatic Generation Script Language Base on Semantic User Annotation (사용자 시맨틱 어노테이션을 이용한 스크립트 언어 자동생성 기법)

  • Song Teuk-Seob;Shin Sung-Wook;Choy Yoon-Chul;Lim Soon-Bum
    • Proceedings of the Korean Information Science Society Conference
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    • 2005.11b
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    • pp.601-603
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    • 2005
  • 2D 또는 3D 아바타는 웹환경에서 효과적인 정보 전달 및 사용자의 흥미 유발등 많은 장점이 있다. 아바타의 다양한 장점을 살려 사이버 교육, 의료, 군사등 다양한 분야에서 응용되고 있다. 아바타를 스크립트 언어를 사용하여 아바타를 제어하고자 하는 연구는 일본 NHK사의 TVML를 비롯하여 AML, CML등 다양한 스크립트 언어가 개발되고 있다. 그러나 기존의 아바타 제어를 위해 개발된 스크립트 언어들은 주로 개발자를 대상으로 개발되어 있어 가상환경이나 스크립트 언어에 익숙하지 않은 최종사용자들이 스크립트 언어를 사용하여 아바타를 제어하는 데는 많은 어려움이 있다. 본 연구에서는 직관적인 인터페이스에 의해 생성된 사용자 정보에 기반하여 자동적으로 스크립트 언어가 생성될 수 있는 기법을 제안 한다.

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Specific Cell-Signal Targets for Cancer Chemotherapy

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.25 no.1
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    • pp.1-10
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    • 2002
  • Attempts to develop drugs, specific for cancer cells, are dealt here according to the intended cell-target. While many target specific drugs were developed, they reach only moderate successes in clinics for reasons, such as, delivery problem, lack of in vivo efficacy or toxicity. However, recent efforts focusing on the diversity of tyrosine kinases, participating in cell-signal transduction, brought fruit. The first such drug, Givec, approved by the USFDA recently, is used in clinics with great success to threat CML. The drug inhibits tyrosin kinase of bcr-abl, c-abl and v-abl. Work is progressing on other tyrosin kinase inhibitors and on other type of specific cancer cell signal protein inhibitors. These efforts are hoped to yield better cures for cancer in the near future.